bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival rate of positive peritoneal cytology in endometrial cancer; a systematic review and meta-analysis
Authors: Dehghan Hamidreza , Binesh Fariba , Moravej Mohammad Taghi , Dehnavi Ali Zare , Dehghanbanadaki Hojat , Heydari Safiyehsadat , Nikfard Maryam , Mansouri Mehrdad
Published: May 2022

Background

The impact of positive peritoneal cytology on survival rate of endometrial cancer patients in different stages and histopathology is still controversial. We performed a systematic review and meta-analysis to investigate the influence of positive peritoneal cytology (PPC) on survival rate of patients with endometrial carcinoma.

Methods

A systematic literature search of PubMed, Embase, Scopus, and Cochrane databases was conducted up to November 24, 2020. The quality of included studies was evaluated by Quality in prognosis study (QUIPS) tool.

Results

Initially, 3014 articles were found, of which 65 met the inclusion criteria for qualitative analysis and 27 studies on 75897 patients with endometrial cancer were included in the meta-analysis. PPC was associated with a lower overall survival in endometrial cancer (HR= 2.102; 95% CI:1.629-2.711; P< 0.001). The findings also identified PPC as an independent prognostic factor for both disease-free survival (HR= 3.052; 95% CI: 2.348-2967; P< 0.001) and cancer specific survival (HR= 3.461; 95% CI: 2.280-5.254; P< 0.001). In addition, we meta-analyzed the studies in 21 subgroups based on staging and histopathology of the endometrial cancer which all identified PPC as a non-prognostic factor for cancer of endometrium.

Conclusion

PPC is an independent prognostic factor for endometrial cancer survival rate in all staging and histopathologic subgroups.
Human health effects of recycling and reusing plastic packaging in the food system: a systematic review and meta-analysis of life cycle assessments
Authors: Deeney Megan , Green Rosemary , Yan Xiaoyu , Dooley Claire , Yates Joe , Rolker Heike B , Kadiyala Suneetha
Published: May 2022

Circular strategies, including recycling and reuse of food packaging, are critical responses to the plastic pollution crisis and could provide co-benefits and trade-offs for human health. Our meta-analysis of life cycle assessment (LCA) data quantifies possible health effects using Disability-Adjusted Life Years (DALYs) mediated by climate change, ozone, air pollution, toxicity, and water scarcity. We found strong evidence for reduced health risks with both a higher percentage of recycled content and a greater end-of-life recycling rate, resulting in around a day of healthy life saved per tonne of plastic packaging recycled. On average, reusable packaging reduced the health impacts associated with single use plastics after 30 uses, which is unlikely reflected in current consumer behaviour. Data from low- and middle-income countries, and greater use of health indicators in LCA, are urgently needed. LCA is a unique tool that could be optimised for interdisciplinary public health research on circular economies.

Teaser

Life cycle assessment meta-analysis shows recycling and reusing plastic food packaging could provide human health co-benefits, and some risks.
Asian Lung Cancer Absolute Risk Models for lung cancer mortality based on China Kadoorie Biobank
Authors: Warkentin Matthew T. , Tammemägi Martin C. , Espin-Garcia Osvaldo , Budhathoki Sanjeev , Liu Geoffrey , Hung Rayjean J.
Published: May 2022

Background

Lung cancer is the leading cause of cancer mortality globally. Early detection through screening can markedly improve prognosis and prediction models can identify high-risk individuals for risk-based screening. However, most models have been developed in North American cohorts of smokers and much less is known about risk factors for never-smokers, which represent a growing proportion of lung cancers, particularly for Asian populations.

Methods

Based on the China Kadoorie Biobank, a population-based prospective cohort study of 512,639 adults age 30-79 recruited between 2004-2008 with up to 12 years of follow-up, we built an Asian Lung Cancer Absolute Risk Model (ALARM) for lung cancer mortality using flexible parametric survival models, separately for ever- and never-smokers, accounting for competing risks of all-other-cause mortality. Model performance was evaluated in a 25% hold-out test set using the time-dependent area under the receiver operating characteristic curve (AUC) and by comparing the model-predicted and observed risks for model calibration.

Results

Predictors assessed in the never-smoker lung cancer mortality model were age, sex, household income, lung function, history of emphysema/bronchitis, family history of cancer, personal cancer history, BMI, passive smoking, and indoor air pollution. The ever-smoker model additionally assessed smoking status (former vs. current), duration, and intensity. The 5-year AUC based on the hold-out test set for the never and ever-smoker models were 0.77 (95% CI: 0.73-0.80) and 0.81 (95% CI: 0.79-0.84), respectively. The maximum 5-year risk for never and ever smokers were 2.6% and 12.7%, respectively.

Conclusions

This study is among the first to develop and test risk models specifically for Asian populations, separately for never (ALARM-NS) and ever-smokers (ALARM-ES). Our models identify Asian never- and ever-smokers at high-risk of death due to lung cancer with a high degree of accuracy and may identify those with risks exceeding common eligibility thresholds who would likely benefit from lung cancer screening.
Systematic searching in Ovid Embase: understanding the MEDLINE document collection and identifying conference records
Authors: Levay Paul
Published: May 2022

Ovid Embase is an important database in systematic searches for health and medical topics. This paper shows how the document collections on Ovid Embase can be used to limit searches and isolate the unique content from MEDLINE that is available on Embase. This is used to test a method for identifying conference records from Embase. The recommended method found 5,108,945 conference records on Embase on Ovid March 1 2022, about 14% of the database. Search strategies are provided for the scenarios that are most likely to be encountered in systematic searches.
Remote working and experiential wellbeing: A latent lifestyle perspective using UK Time Use Survey before and during COVID-19
Authors: Chen Jerry , Wan Li
Published: May 2022

Mental health in the UK had deteriorated compared with pre-pandemic trends. Existing studies on heterogenous wellbeing impacts of COVID-19 tend to segment population based on isolated socio-economic and demographic indicators, typically gender, income and ethnicity, while a more holistic understanding of such heterogeneity among the workforce seems lacking. This study addresses this gap by 1) combining UK time use surveys collected before and during COVID-19, 2) identifying nuanced lifestyles within three working mode groups (commuters, homeworkers and hybrid workers) using latent class model, and 3) quantifying heterogeneous experiential wellbeing (ExWB) impacts across workers of distinct lifestyles. It was found that the direction and magnitude of ExWB impact were not uniform across activity types, time of day and lifestyles. ExWB impact outside of usual working hours (before 6am and after 6pm) was consistently negative for all lifestyles. In contrast, the direction of ExWB impact during usual working hours (6am-6pm) varied in accordance with lifestyle classifications. Specifically, ExWB decreased for all homeworkers but increased significantly for certain hybrid workers. Magnitude of ExWB impact correlated strongly with lifestyle: the optionality of choosing one’s place of work and the associated ability to travel during the pandemic seemed to improve ExWB. To understand the significant heterogeneity in ExWB outcomes, a spatial-temporal conceptualisation of working flexibility is developed to explicate the strong yet complex correlations between wellbeing and lifestyles. Whilst greater spatio-temporal flexibility is generally linked to increase in workers’ ExWB, there is preliminary evidence of a flexibility threshold – above which the marginal ExWB increase would diminish and even become negative. The implications to post-pandemic “back-to-work” policies are 1) shifting policy focus from simplistic workplace choice to spatial-temporal optionality (i.e. lifestyle choice), and 2) providing wider support for lifestyle adaptation and transitions.
Tanycytes are degraded in Alzheimer’s Disease, disrupting the brain-to-blood efflux of Tau
Authors: Sauvé Florent , Ternier Gaëtan , Dewisme Julie , Lebouvier Thibaut , Dupré Elian , Danis Clément , Rasika S. , Kim Young-Bum , Ciofi Philippe , Giacobini Paolo , Buée Luc , Landrieu Isabelle , Pasquier Florence , Maurage Claude-Alain , Nogueiras Ruben , Schwaninger Markus , Prevot Vincent
Published: May 2022

The accumulation of pathological Tau in the brain and cerebrospinal fluid (CSF) and its eventual increase in the blood are hallmarks of Alzheimer’s disease (AD). However, the mechanisms of Tau clearance from the brain to the periphery are not clear. We show here, using animal and cellular models as well as patient blood samples and post mortem brains, that hypothalamic tanycytes, whose cell bodies line the ventricular wall and send long processes to the underlying pituitary portal capillary bed, take up and transport Tau from the CSF and release it into these capillaries, whence it travels to the pituitary and eventually the systemic circulation. Specifically blocking tanycytic vesicular transport leads to an accumulation of exogenous fluorescent Tau in the CSF of mice. In AD and frontotemporal dementia, tanycytic morphology is altered, with a dramatic fragmentation of the secondary cytoskeleton in the former but not the latter, accounting for reduced CSF Tau clearance in AD. Both the implication of tanycytic degradation in the pathophysiology of a human disease and the evidence for the existence of a brain-to-blood tanycytic shuttle are unprecedented, and raise important questions regarding the role of tanycytes in physiological clearance mechanisms and the development of neurodegenerative disorders.
Effective screening strategies for safe opening of universities under Omicron and Delta variants of COVID-19
Authors: Rabil Marie Jeanne , Tunc Sait , Bish Douglas R. , Bish Ebru K.
Published: May 2022

As new COVID-19 variants emerge, and disease and population characteristics change, screening strategies may also need to change. We develop a decision-making model that can assist a college to determine an optimal screening strategy based on their characteristics and resources, considering COVID-19 infections/hospitalizations/deaths; peak daily hospitalizations; and the tests required. We also use this tool to generate screening guidelines for the safe opening of college campuses. Our compartmental model simulates disease spread on a hypothetical college campus under co-circulating variants with different disease dynamics, considering: (i) the heterogeneity in disease transmission and outcomes for faculty/staff and students based on vaccination status and level of natural immunity; and (ii) variant- and dose-dependent vaccine efficacy. Using the Spring 2022 academic semester as a case study, we study routine screening strategies, and find that screening the faculty/staff less frequently than the students, and/or the boosted and vaccinated less frequently than the unvaccinated, may avert a higher number of infections per test, compared to universal screening of the entire population at a common frequency. We also discuss key policy issues, including the need to revisit the mitigation objective over time, effective strategies that are informed by booster coverage, and if and when screening alone can compensate for low booster coverage.
“Does a respiratory virus have an ecological niche, and if so, can it be mapped?” Yes and yes
Authors: Stephens Christopher R. , González-Salazar Constantino , Martínez Pedro Romero
Published: May 2022

Although the utility of Ecological Niche models (ENM) and Species Distribution models (SDM) has been demonstrated in many ecological applications, their suitability for modelling epidemics or pandemics, such as SARS-Cov-2, has been questioned. In this paper, contrary to this viewpoint, we show that ENMs and SDMs can be created that can describe the evolution of pandemics, both in space and time. As an illustrative use case, we create models for predicting confirmed cases of COVID-19, viewed as our target “species”, in Mexico through 2020 and 2021, showing that the models are predictive in both space and time. In order to achieve this, we extend a recently developed Bayesian framework for niche modelling, to include: i) dynamic, non-equilibrium “species” distributions; ii) a wider set of habitat variables, including behavioural, socio-economic and socio-demographic variables, as well as standard climatic variables; iii) distinct models and associated niches for different species characteristics, showing how the niche, as deduced through presence-absence data, can differ from that deduced from abundance data. We show that the niche associated with those places with the highest abundance of cases has been highly conserved throughout the pandemic, while the inferred niche associated with presence of cases has been changing. Finally, we show how causal chains can be inferred and confounding identified by showing that behavioural and social factors are much more predictive than climate and that, further, the latter is confounded by the former.
Post-translational modifications glycosylation and phosphorylation of the major hepatic plasma protein fetuin-A are associated with severity of CNS inflammation in children
Authors: Ricken Frederik , Can Ahu Damla , Gräber Steffen , Häusler Martin , Jahnen-Dechent Willi
Published: May 2022

Background

Fetuin-A is a liver derived plasma protein showing highest serum concentrations in utero, preterm infants and neonates. Fetuin-A is also present in cerebrospinal fluid (CSF). The origin of CSF fetuin-A, blood-derived via the blood brain barrier or synthesized intrathecally, is presently unclear. Fetuin-A prevents ectopic calcification by stabilizing calcium and phosphate as colloidal calciprotein particles mediating their transport and clearance. Thus, fetuin-A plays a suppressive role in inflammation. Fetuin-A is a negative acute-phase protein, serving as a biomarker for MS. Here we studied the association of pediatric inflammatory CNS diseases with fetuin-A glycosylation and phosphorylation.

Methods

Paired blood and CSF samples from 66 children were included in the study. Concentration measurements were performed using a commercial human fetuin-A/AHSG ELISA. Of 60 pairs, 23 pairs were analyzed by SDS-PAGE following glycosidase digestion with PNGase-F and Sialidase-AU. Phosphorylation was analyzed in 30 pairs by Phos-Tag™ acrylamide electrophoresis following alkaline phosphatase digestion.

Results and Discussion

Mean serum and CSF fetuin-A levels were 0.30 ± 0.06 mg/ml and 0.644 ± 0.55 µg/ml, respectively. This study showed that serum fetuin-A levels decreased in inflammation corroborating its role as a negative acute-phase protein. Blood-brain barrier disruption was associated with elevated fetuin-A in CSF. A strong positive correlation was found between the CSF fetuin-A/serum fetuin-A ratio and the CSF albumin/serum albumin ratio, suggesting predominantly transport across the blood-brain barrier rather than intrathecal fetuin-A synthesis. Sialidase digestion showed increased asialofetuin-A levels in serum and CSF samples from children with neuroinflammatory diseases. Desialylation enhanced hepatic fetuin-A clearance via the asialoglycoprotein receptor thus rapidly reducing serum levels during inflammation. Phosphorylation of fetuin-A was more abundant in serum samples than in CSF, suggesting that phosphorylation may regulate fetuin-A influx into the CNS. These results may help establish Fetuin-A as a potential biomarker for neuroinflammatory diseases.
Repurposing EEG monitoring of general anaesthesia for building biomarkers of brain ageing: An exploratory study
Authors: Sabbagh David , Cartailler Jérôme , Touchard Cyril , Joachim Jona , Mebazaa Alexandre , Vallée Fabrice , Gayat Étienne , Gramfort Alexandre , Engemann Denis A.
Published: May 2022

Background

EEG is a common tool for monitoring anaesthetic depth but is rarely reused at large for biomedical research. This study sets out to explore repurposing of EEG during anaesthesia to learn biomarkers of brain ageing in the absence of consciousness.

Methods

We focused on brain age estimation as an example. Using machine learning, we reanalysed 4-electrodes EEG of 323 patients under propofol and sevoflurane. We included spatio-spectral features from stable anaesthesia for EEG-based age prediction applying recently published reference methods. Anaesthesia was considered stable when 95% of the total power was below a frequency between 8Hz and 13Hz.

Results

We considered moderate-risk patients (ASA <= 2) with propofol anaesthesia to explore predictive EEG signatures. Average alpha-band power (8-13Hz) was informative about age. Yet, state-of-the-art prediction performance was achieved by analysing the entire power spectrum from all electrodes (MAE = 8.2y, R2 = 0.65). Clinical exploration revealed that brain age was systematically linked with intra-operative burst suppression – commonly associated with age-related postoperative cognitive issues. Surprisingly, the brain age was negatively correlated with burst suppression in high-risk patients (ASA = 3), pointing at unknown confounding effects. Secondary analyses revealed that brain-age EEG signatures were specific to propofol anaesthesia, reflected by limited prediction performance under sevoflurane and poor cross-drug generalisation.

Conclusions

EEG from general anaesthesia may enable state-of-the-art brain age prediction. Yet, differences between anaesthetic drugs can impact the effectiveness of repurposing EEG from anaesthesia. To unleash the dormant potential of repurposing EEG-monitoring for clinical and health research, in the absence of consciousness, collecting larger datasets with precisely documented drug dosage will be key enabling factors.
The I-SPY COVID Adaptive Platform Trial for COVID-19 Acute Respiratory Failure: Rationale, Design and Operations
Authors: Files D. Clark , Matthay Michael A. , Calfee Carolyn S. , Aggarwal Neil , Asare Adam L. , Beitler Jeremy R. , Berger Paul A. , Burnham Ellen L. , Cimino George , Coleman Melissa H. , Crippa Alessio , Discacciati Andrea , Gandotra Sheetal , Gibbs Kevin W. , Henderson Paul T. , Ittner Caroline A.G. , Jauregui Alejandra , Khan Kashif T. , Koff Jonathan L. , Lang Julie , LaRose Mary , Levitt Joe , Lu Ruixiao , McKeehan Jeffrey D. , Meyer Nuala J. , Russell Derek W. , Thomas Karl W. , Eklund Martin , Esserman Laura J. , Liu Kathleen D.
Published: May 2022

Introduction

The COVID-19 pandemic brought an urgent need to discover novel effective therapeutics for patients hospitalized with severe COVID-19. The ISPY COVID trial was designed and implemented in early 2020 to evaluate investigational agents rapidly and simultaneously on a phase 2 adaptive platform. This manuscript outlines the design, rationale, implementation, and challenges of the ISPY COVID trial during the first phase of trial activity from April 2020 until December 2021.

Methods and analysis

The ISPY COVID Trial is a multi-center open label phase 2 platform trial in the United States designed to evaluate therapeutics that may have a large effect on improving outcomes from severe COVID-19. The ISPY COVID Trial network includes academic and community hospitals with significant geographic diversity across the country. Enrolled patients are randomized to receive one of up to four investigational agents or a control and are evaluated for a family of two primary outcomes—time to recovery and mortality. The statistical design uses a Bayesian model with “stopping” and “graduation” criteria designed to efficiently discard ineffective therapies and graduate promising agents for definitive efficacy trials. Each investigational agent arm enrolls to a maximum of 125 patients per arm and is compared to concurrent controls. As of December 2021, 11 investigational agent arms had been activated, and 8 arms were complete. Enrollment and adaptation of the trial design is ongoing.

Ethics and dissemination

ISPY COVID operates under a central institutional review board via Wake Forest School of Medicine IRB00066805. Data generated from this trial will be reported in peer reviewed medical journals.

Trial registration number

Clinicaltrials.gov registration number NCT04488081

Strengths and limitations of this study

The ISPY COVID Trial was developed in early 2020 to rapidly and simultaneously evaluate therapeutics for severe COVID-19 on an adaptive open label phase 2 platform

The ISPY COVID Adaptive Platform Trial Network is an academic-industry partnership that includes academic and community hospitals spanning a wide geographic area across the United States

Of December 2021, 11 investigational agent arms have been activated on the ISPY COVID Trial Platform

The ISPY COVID Trial was designed to identify therapeutic agents with a large clinical effect for further testing in definitive efficacy trials—limitations to this approach include the risk of a type 2 error
Impaired visual processing in psychosis patients with a predisposition for visual hallucinations
Authors: van Ommen Marouska , Marsman Jan Bernard , Renken Remco , Bruggeman Richard , van Laar Teus , Cornelissen Frans W.
Published: May 2022

Psychosis is frequently associated with the occurrence of visual hallucinations (VH), but their etiology remains largely unknown. While patients with psychosis show deficits on various behavioral visual and attentional tasks, previous studies have not specifically related these deficits to the presence of VH. This suggests that tasks used in these studies do not target the visual-cognitive neural mechanisms that mediate VH, which in turn limits the development of effective therapies. We therefore designed a study to target these mechanisms directly. In this case control study we asked patients with psychosis who had previously experienced VH to indicate when they recognized objects that were gradually emerging from dynamic visual noise, while scanning their brains using functional Magnetic Resonance Imaging. In a previous study, this recognition task was used to identify the neural basis of VH in patients with Parkinson’s Disease. Based on this earlier work, we decided to test the following hypothesis: when compared to psychosis patients not experiencing VH and age-matched healthy controls, psychosis patients with VH show reduced occipital activity and frontal activity around the moment of recognition (known as pop-out). For all groups, neuroimaging revealed increased activity in all examined visual areas around pop-out. However, psychosis patients with VH showed reduced occipital responsiveness, especially in the inferior part of the bilateral lateral occipital complex, a region known to play a key role in object recognition. We did not observe altered frontal or prefrontal activity before pop-out in this group. A possible explanation is that the relatively sustained activation of the visual memory-related angular gyri around pop-out may have compensated for the impaired early visual processing in psychosis patients with VH. We discuss our results in terms of current theories of visual hallucinations, such as predictive coding and contextual modulation. Our study is the first to show that visual processing deficits contribute to the occurrence of VH in psychosis. These findings could be used to develop tests to identify the visual-cognitive mechanisms that mediate VH in this group.
Construction of a short version of the Montreal Cognitive Assessment (MoCA) rating scale using Partial Least Squares analysis
Authors: Hemrungrojn Solaphat , Amrapala Arisara , Maes Michael
Published: May 2022

Background

The Montreal Cognitive Assessment (MoCA) rating scale is frequently used to assess cognitive impairments in amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD).

Objectives

The aims of this study are to a) evaluate the construct validity of the MoCA and its subdomains or whether the MoCA can be improved by feature reduction, and b) develop a short version of the MoCA (MoCA-Brief).

Methods

We recruited 181 participants, divided into 60 healthy controls, 61 aMCI, and 60 AD patients.

Results

The construct reliability of the original MoCA was not optimal and could be improved by deleting one subdomain (Naming) and five items, namely Clock Circle, Lion, Digit Forward, Repeat 2nd Sentence, and Place, which showed inadequate loadings on the extracted latent vectors. To construct the MoCA-Brief, the reduced model underwent further reduction and feature selection based on model quality data of the outer models. We produced a MoCA-Brief rating scale comprising five items, namely Clock Time, Subtract 7, Fluency, Month, and Year. The first latent vector extracted from these five indicators showed adequate construct validity with an Average Variance Extracted of 0.599, composite reliability of 0.822, Cronbach’s alpha of 0.832 and rho_A of 0.833. The MoCA-Brief factor score showed a strong correlation with the total MoCA score (r=0.98, p<0.001) and shows adequate concurrent, test-retest, and inter-rater validity.

Conclusion

The construct validity of the MoCA may be improved by deleting five items. The new MoCA-Brief rating scale deserves validation in independent samples and especially in other countries.
Factors associated with repeat childbirth among Adolescent Mothers in Soroti District, Teso sub-region, Uganda: A cross-sectional study
Authors: Mulalu Posiano , Wanume Benon , David Soita , Amongin Dinnah , Wandawa Gabriel Julius
Published: May 2022

The percentage of adolescent mothers aged 15 to 19 years with a repeat childbirth in Uganda (26.1%) is higher than the global estimate (18.5%). Soroti district tops Teso (a region with highest adolescent childbearing rate nationally) in adolescent childbearing. Adolescent repeat childbearing (ARC) is associated with poor health outcomes, increased risk of stillbirth, maternal and child mortality, thus a public health concern. The factors associated with, and the burden, of ARC remains unknown in Soroti district. Consequently, interventions which combat ARC in Soroti district have not been informed by empirical data. This study determined the proportion of adolescent mothers with, and factors associated with, repeat childbirth among adolescent mothers in Soroti district.

We conducted a cross-sectional study involving mixed methods of data collection. Interviewer-administered structured interviews were conducted amongst 422 adolescent mothers.

Demographic and socio-economic data of respondents, data regarding respondents’ family and peer related factors was collected. Chi-square was the test statistics used. Multivariate analysis was by logistic regression.

Of the 422 respondents, 31.28% (132) were married. Proportion of respondents with repeat childbirth was at 30.81% (95%CI: 26.57%-35.39%). Risk factors of ARC were (a) being married, AOR 5.74 (95%CI: 3.08-10.68), (b) incorrect knowledge of rhythm method, AOR 2.15 (95%CI: 1.21-3.82), (c) Age at first birth, AOR 0.48 (95%CI: 0.36-0.63). Protective factors of ARC included (a) not drinking alcohol, AOR 0.41(95%CI: 0.21-0.77), not being raped, AOR 0.19(95%CI: 0.06-0.55), having first childbirth from health facility, AOR 0.38 (95%CI: 0.18-0.78) and father of first baby without multiple sexual partners, AOR 0.40(95%CI: 0.22-0.72).

In conclusion, sexual partner characteristics were associated with ARC suggesting male involvement (for example in family planning) in prevention of ARC. In addition, strengthening the implementation of anti-teen marriage programs and alcohol consumption policies, and instating measures to delay age at first delivery among adolescent mothers are required. Further research is needed to validate these findings.
Datasets for a Simulated Family-Based Exome-Sequencing Study
Authors: Dona Nirodha Epasinghege , Graham Jinko
Published: May 2022

We present simulated exome-sequencing data for 150 families from a North American admixed population, ascertained to contain at least four members affected with lymphoid cancer. These data include information on the ascertained families as well as single-nucleotide variants on the exome of affected family members. We provide a brief overview of the simulation steps and links to the associated software scripts. The resulting data are useful to identify genomic patterns and disease inheritance in families with multiple disease-affected members.

Specifications Table
TCR repertoire profiling revealed antigen-driven CD8+ T cell clonal groups shared in synovial fluid of patients with spondyloarthritis
Authors: Komech Ekaterina A. , Koltakova Anastasia D. , Barinova Anna A. , Minervina Anastasia A. , Salnikova Maria A. , Shmidt Evgenia I. , Korotaeva Tatiana V. , Loginova Elena Y. , Erdes Shandor F. , Bogdanova Ekaterina A. , Shugay Mikhail , Lukyanov Sergey , Lebedev Yury B. , Zvyagin Ivan V.
Published: May 2022

Spondyloarthritis (SpA) comprises a number of inflammatory rheumatic diseases with overlapping clinical manifestations. Strong association with several HLA-I alleles and T cell infiltration into an inflamed joint suggest involvement of T cells in SpA pathogenesis. In this study, we performed high-throughput T cell repertoire profiling of synovial fluid (SF) and peripheral blood (PB) samples collected from a large cohort of SpA patients. We showed that synovial fluid is enriched with expanded T cell clones that are shared between patients with similar HLA genotypes and persist during recurrent synovitis. Using the recently published algorithm we discovered antigen-driven CD8+ clonal groups associated with risk HLA-B*27 or HLA-B*38 alleles. These clonal groups were enriched in SF and had higher frequency in PB of SpA patients vs healthy donors, suggesting their relevance to joint inflammation. Several of the identified groups were shared among patients with ankylosing spondylitis and psoriatic arthritis, suggesting existence of a common immunopathological mechanism of the diseases. In summary, our results provide supporting evidence for the role of antigen-driven CD8+ T cell clones in pathogenesis of SpA.
STIMULATE-ICP-CAREINEQUAL - Defining usual care and examining inequalities in Long Covid support: protocol for a mixed-methods study (part of STIMULATE-ICP: Symptoms, Trajectory, Inequalities and Management: Understanding Long-COVID to Address and Transform Existing Integrated Care Pathways)
Authors: Ramasawmy Mel , Mu Yi , Clutterbuck Donna , Pantelic Marija , Lip Gregory Y. H. , van der Feltz-Cornelis Christina , Wootton Dan , Williams Nefyn H , Montgomery Hugh , Cookson Rita Mallinson , Attree Emily , Gabbay Mark , Heightman Melissa , Alwan Nisreen A , Banerjee Amitava , Lorgelly Paula ,   the STIMULATE-ICP consortium
Published: May 2022

Introduction

Individuals with Long Covid represent a new and growing patient population. In England, fewer than 90 Long Covid clinics deliver assessment and treatment informed by NICE guidelines. However, a paucity of clinical trials or longitudinal cohort studies means that the epidemiology, clinical trajectory, healthcare utilisation and effectiveness of current Long Covid care are poorly documented, and that neither evidence-based treatments nor rehabilitation strategies exist. In addition, and in part due to pre-pandemic health inequalities, access to referral and care varies, and patient experience of the Long Covid care pathways can be poor.

In a mixed methods study, we therefore aim to: (1) describe the usual healthcare, outcomes and resource utilisation of individuals with Long Covid; (2) assess the extent of inequalities in access to Long Covid care, and specifically to understand Long Covid patients’ experiences of stigma and discrimination.

Methods and analysis

A mixed methods study will address our aims. Qualitative data collection from patients and health professionals will be achieved through surveys, interviews and focus group discussions, to understand their experience and document the function of clinics. A patient cohort study will provide an understanding of outcomes and costs of care. Accessible data will be further analysed to understand the nature of Long Covid, and the care received.

Ethics and dissemination

Ethical approval was obtained from South Central - Berkshire Research Ethics Committee (reference 303958). The dissemination plan will be decided by the patient and public involvement and engagement (PPIE) group members and study Co-Is, but will target 1) policy makers, and those responsible for commissioning and delivering Long Covid services, 2) patients and the public, and 3) academics.
Use of low-dose decitabine with or without tyrosine kinase inhibitors in advanced phase chronic myelogenous leukemia: a systemic review and metaanalysis
Authors: Comia Maureen Via M. , Sy Charles Eryll S. , Julian Jomell C.
Published: May 2022

Rationale

Progression of Chronic Myelogenous Leukemia (CML) to more advanced phases can involve hypermethylation, which is correlated to resistance or intolerance to imatinib. This hypermethylation has also been found to be a negative prognostic factor independent of imatinib response and from CML phase, thus decitabine, a hypomethylating agent, can be an attractive treatment option for advanced phase CML.

Objective

This systemic review and meta-analysis aims to investigate the role of low-dose decitabine among patients with advanced phase CML.

Methodology

This was performed according to the statement of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)

Results

Four (4) studies from 86 articles screened were eligible to be assessed in this systemic review and meta-analysis. These were phase I/II trials involving 81 advanced phase CML patients and used low-dose decitabine (5 to 20 mg/m2), with two studies using tyrosine kinase inhibitors. Outcomes of hematologic and cytogenetic response, and survival were assessed in the meta-analysis; with hematologic response being favored among advanced phase CML patients upon exposure with low-dose decitabine (p=0.05). Survival was also favored among responders to low-dose decitabine, however this was not significant.

Discussion and Conclusion

Low-dose decitabine can be an effective and safe treatment option in advanced phase CML, especially in more frail patients that could not tolerate more intensive chemotherapy regimens. However, this study is limited by few studies available on this topic, thus further randomized controlled trials can be investigated to define the role of decitabine and its optimal dose among this subset of patients.
Comparing human and AI performance in medical machine learning: An open-source Python library for the statistical analysis of reader study data
Authors: McKinney Scott Mayer
Published: May 2022

In seeking to understand the potential effects of artificial intelligence (AI) on the practice of diagnostic medicine, many investigations involve collecting interpretations from several human experts on a common set of cases. In an effort to standardize the process of analyzing the data emerging from such studies, we have released an open-source Python library to perform applicable statistical procedures. The software implements the industry-standard Obuchowski-Rockette-Hillis (ORH) method for multi-reader multi-case (MRMC) studies. The tools can be used to compare a standalone algorithm against a panel of readers, or compare readers operating in two modalities (for example, with and without algorithmic assistance). The software supports both nonequivalence and noninferiority tests. Functions are also provided to simulate reader and model scores, useful for Monte Carlo power analysis. The code is publicly available in our Gitub repository at https://github.com/Google-Health/google-health/tree/master/analysis.
Perceptions of adolescent mothers towards adolescent repeat childbirth in Soroti District, Teso sub-region, Uganda: A phenomenological study
Authors: Mulalu Posiano , Wanume Benon , David Soita , Amongin Dinnah , Wandawa Gabriel Julius
Published: May 2022

The percentage of adolescent mothers aged 15 to 19 years with a repeat childbirth in Uganda (26.1%) is higher than the global estimate (18.5%). Soroti district tops Teso (a region with highest adolescent childbearing rate nationally) in adolescent childbearing. Adolescent repeat childbearing (ARC) is associated with poor health outcomes, increased risk of stillbirth, maternal and child mortality, thus a public health concern. The explanations to the high prevalence of repeat childbirth in Soroti district remain unknown.

We conducted a phenomenological study where theoretical saturation was achieved with 3 focus group discussions; each comprised of 8 respondents. Transcripts were organized and analyzed by QSR Nvivo following deductive approach.

Results

Adolescent marriage was viewed as a privilege, family planning methods were viewed as non-functional, man’s demand for sex was unchallengeable and non-supportive families including mistreatment of the participants by their families were perceived as risk factors for ARC.

This therefore suggests that in order to prevent repeat adolescent childbearing in Soroti district, and contribute towards the achievement of the SDG numbered three (ensure healthy lives and promote well-being for all at all ages) there is need to awaken and strengthen the implementation of the anti-teen marriage programs and policies; strengthen sexual/reproductive education including family planning programs, and addressing identified myths regarding ARC.

We also recommend further research to be done in Uganda, especially in other districts of Teso region to validate our findings.
mRNA-based COVID-19 booster vaccination is highly effective and cost-effective in Australia
Authors: Li Rui , Liu Hanting , Fairley Christopher K , Ong Jason J , Guo Yuming , Zou Zhuoru , Xie Li , Zhuang Guihua , Li Yan , Shen Mingwang , Zhang Lei
Published: May 2022

Background

Australia implemented an mRNA-based booster vaccination strategy against the COVID-19 Omicron variant in November 2021. We aimed to evaluate the effectiveness and cost-effectiveness of the booster strategy over 180 days.

Methods

We developed a decision-analytic Markov model of COVID-19 to evaluate the cost-effectiveness of a booster strategy (administered 3 months after 2nd dose) in those aged ≥16 years in Australia from a healthcare system perspective. The willingness-to-pay threshold was chosen as A$ 50,000.

Findings

Compared with 2-doses of COVID-19 vaccines without a booster, Australia’s booster strategy would incur an additional cost of A$0.88 billion but save A$1.28 billion in direct medical cost and gain 670 quality-adjusted life years (QALYs) in 180 days of its implementation. This suggested the booster strategy is cost-saving, corresponding to a benefit-cost ratio of 1.45 and a net monetary benefit of A$0.43 billion. The strategy would prevent 1.32 million new infections, 65,170 hospitalisations, 6,927 ICU admissions and 1,348 deaths from COVID-19 in 180 days. Further, a universal booster strategy of having all individuals vaccinated with the booster shot immediately once their eligibility is met would have resulted in a gain of 1,599 QALYs, a net monetary benefit of A$1.46 billion and a benefit-cost ratio of 1.95 in 180 days.

Interpretation

The COVID-19 booster strategy implemented in Australia is likely to be effective and cost-effective for the Omicron epidemic. Universal booster vaccination would have further improved its effectiveness and cost-effectiveness.

Funding

National Natural Science Foundation of China. Bill and Melinda Gates Foundation
Long-term ambient hydrocarbon exposure and incidence of urinary bladder cancer
Authors: Zhang Han-Wei , Tsai Zhi-Ren , Kok Victor C , Peng Hsiao-Ching , Chen Yau-Hung , Tsai Jeffrey JP , Hsu Chun-Yi
Published: May 2022

Background

Particulate matter and volatile organic compounds, including total hydrocarbons (THCs), are major ambient air pollutants. The primary nonmethane hydrocarbons (NMHCs) originate from vehicle emissions. Studies on the association between air pollution and urinary bladder cancer (UBC) have revealed contradictory results.

Objectives

The present study investigated whether long-term exposure to ambient hydrocarbons increases UBC risk among people aged ≥20 years in Taiwan.

Methods

Linkage dataset research with longitudinal design was conducted on 600,666 cancer-free individuals from 2000–2013; 12 airborne pollutants were determined. Several Cox models considering potential confounders were employed. The study outcomes were invasive or in situ UBC incidence over time. The targeted pollutant concentration was divided into three tertiles: T1/T2/T3.

Results

The mean age of the individuals at risk was 42.8 (SD, 15.7), and 50.2% were men. The mean daily average over 10-years of airborne THC concentration was 2.24 ppm (SD, 0.14), and NMHC was 0.29 ppm (SD, 0.09). There was a dose-dependent increase in UBC at follow-up. The incidence of UBC cases per 100,000 people by T1/T2/T3 exposure to THC was 60.3, 203.7, and 450.8, respectively; it was 180.2/202.4/453.8 per 100,000, corresponding to T1/T2/T3 exposure to NMHC, respectively. Without controlling for confounding air pollutants, the adjusted hazard ratio (adj.HR) was 1.77 (95% CI, 1.69–1.87) per 0.14 ppm increase of THC; after controlling for PM2.5, adj.HR was even higher at 2.10 (95% CI, 1.99– 2.22). The adj.HR was 1.38 (95% CI, 1.31–1.44) per 0.09 ppm increase in ambient NMHC concentration. After controlling for SO2 and CH4, the adj.HR was 1.16 (95% CI, 1.11–1.21). Sensitivity analyses showed that the UBC development risk was not sex-specific or influenced by diabetes status.

Discussion

Long-term exposure to THC and NMHC may be a risk factor for UBC development. Acknowledging the pollutant sources can inform risk management strategies.
Genomic summary statistics and meta-analysis for set-based gene-environment interaction tests in large-scale sequencing studies
Authors: Wang Xinyu , Pham Duy T. , Westerman Kenneth E. , Pan Cong , Manning Alisa K. , Chen Han
Published: May 2022

We propose an efficient method to generate the summary statistics for set-based gene-environment interaction tests, as well as a meta-analysis approach that aggregates the summary statistics across different studies, which can be applied to large biobank-scale sequencing studies with related samples. Simulations showed that meta-analysis is numerically concordant with the equivalent pooled analysis using individual-level data. Moreover, meta-analysis accommodates heterogeneity between studies and enhances power in multi-ethnic studies. We applied the meta-analysis approach to the whole-exome sequencing data from the UK Biobank and successfully identified gene regions associated with waist-hip ratio, as well as those with sex-specific genetic effects.
The impact of rapid near-patient STI testing on service delivery outcomes: a controlled interrupted time series study
Authors: Walter Scott R , Jackson Joni , Myring Gareth , Redaniel Maria Theresa , Margelyte Ruta , Gardiner Rebecca , Clarke Michael D , Crofts Megan , McLeod Hugh , Hollingworth William , Phillips David , Muir Peter , Steer Jonathan , Turner Jonathan , Horner Patrick J , de Vocht Frank
Published: May 2022

Objectives

To evaluate the impact of a new clinic-based rapid STI testing, diagnosis and treatment service on healthcare delivery and resource needs in a sexual health service.

Design

Controlled interrupted time series study.

Setting

Two sexual health services in UK: Unity Sexual Health in Bristol, UK (main site) and Croydon Sexual Health in London (control site).

Participants

Electronic patient records for all attendances during the period one year before and one year after the intervention.

Intervention

Introduction of an in-clinic rapid testing system for gonorrhoea and chlamydia in combination with revised treatment pathways.

Outcome measures

Time-to-test notification, staff capacity, cost per episode of care and overall service costs. We also assessed rates of gonorrhoea culture swabs, follow-up attendances, and examinations.

Results

Time-to-notification and the rate of gonorrhoea swabs significantly decreased following implementation of the new system. There was no evidence of change in follow-up visits or examination rates for patients seen in clinic related to the new system. Staff capacity in clinics appeared to be maintained across the study period. Overall, the number of episodes per week was unchanged in the Unity SHS, and the mean cost per episode decreased by 7.5% (95%CI 5.7%, 9.3%). Conclusions: The clear improvement in time-to-notification, while maintaining activity at a lower overall cost, suggests that the implementation of clinic-based testing in parallel to postal testing kits had the intended impact, which bolsters the case for more widespread rollout in SHS.

Strengths and limitations of this study

We used controlled interrupted time series models with confounder adjustment to estimate the effect of the intervention distinct from any background changes and independent of other time varying factors.

Model validity was bolstered by using a relatively long time series with good temporal resolution.

Data from both the main and control sites was derived from the same electronic patient record system.

There was a general consensus between main and sensitivity analyses.

Our study was limited by being non-randomised, having only one control site, and the follow up period for females being truncated by the impact of the Covid-19 pandemic.
Understanding Health worker Perspectives on Risk Screening for HIV Testing - A Qualitative Study from Zimbabwe
Authors: Mugauri Hamufare D. , Chirenda Joconiah , Takarinda Kudakwashe , Mugurungi Owen , Ncube Getrude , Chikondowa Ishmael , Mantiziba Patrick , Tshimanga Mufuta
Published: May 2022

Background

The use of screening tools during targeted human immunodeficiency virus (HIV) testing services improves efficiency by identifying individuals who are likely to test positive. Effective utilization of screening tools requires an understanding of health care worker perception and willingness to use the tools. We determined health workers’ perspectives on screening tools to enhance their effective and consistent utilisation.

Methods

We conducted a qualitative study among healthcare workers at 8 selected primary healthcare facilities in Zimbabwe. Interviewer guided, in-depth interviews were conducted with healthcare workers and their immediate supervisors. Inductive and deductive coding (hybrid) was applied to develop and analyze themes following a framework built around the grounded theory model to describe perspectives that influence the effective and consistent utilization of HIV screening tools and suggestions for improved eligibility screening.

Results

Behavioural factors facilitating the utilisation of the screening tool included motivation to adhere to standard practice, awareness of screening role in targeting testing, and its ability to manage workload through screening out ineligible clients. This was evident across service delivery levels. Barriers included limited healthcare capacity, confidentiality space, multiple screening tools and opaque screening in/out criteria and the potential of clients not responding to screening questions truthfully.

Conclusions

Across geographical and service delivery levels, correct placing of the screening tool at HIV testing entry point, healthcare worker knowledge on screening in/out criteria emerged as enablers for correct and consistent use of the screening tools. Further, standardizing the tools used would improve the utilisation of the correct tool.