bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integration of hyperspectral imaging and transcriptomics from individual cells with HyperSeq
Authors: Xie Yike , Habibalahi Abbas , Anwer Ayad G. , Wahi Kanu , Gatt Catherine , Johansson Emma M. V. , Holst Jeff , Goldys Ewa , Zanini Fabio 
Published: January 2024

AbstractMicroscopy and omics are complementary approaches to probe the molecular state of cells in health and disease, combining granularity with scalability. While important advances have been achieved over the last decade in each area, integrating both imaging- and sequencing-based assays on the same cell has proven challenging. In this study, a new approach called HyperSeq that combines hyperspectral autofluorescence imaging with transcriptomics on the same cell is demonstrated. HyperSeq was applied to Michigan Cancer Foundation 7 (MCF-7) breast cancer cells and identified a subpopulation of cells exhibiting bright autofluorescence rings at the plasma membrane in optical channel 13 (λex= 431 nm,λem= 594 nm). Correlating the presence of a ring with the gene expression in the same cell indicated that ringed cells are more likely to express hallmark genes of apoptosis and less likely to express genes associated with ATP production. Further, correlation of cell morphology with gene expression suggested that multiple members of the spliceosome were downregulated in larger MCF-7 cells. Multiple genes were evenly expressed across cell sizes but also exhibited higher usage of specific exons in larger or smaller cells. Finally, correlation between gene expression and fluorescence within the spectral range of Nicotinamide adenine dinucleotide hydrogen (NADH) provided insight into the metabolic states of MCF-7 cells. These observations provided a link between the cell’s optical spectrum and its internal molecular state, demonstrating the utility of HyperSeq to study cell biology at single cell resolution by integrating spectral, morphological and transcriptomic analyses into a single, streamlined workflow.
Policy approaches to decarbonising the transport sector in Aotearoa/NZ: Equity, health and health system impacts
Authors: Shaw Caroline , Mizdrak Anja , Gage Ryan , McLeod Melissa , Jones Rhys , Woodward Alistair , Cobiac Linda 
Published: January 2024

AbstractBackgroundHealth co-benefits are a key potential advantage of transport decarbonisation policy. However, health impacts will occur in the context of existing transport-health inequities and decarbonisation policies will themselves impact inequities.MethodsWe modelled the health, health system and environmental impacts of the ‘Behaviour’ and ‘Technology’ pathways developed by the New Zealand Climate Change Commission. Household transport related health impacts were modelled through the pathways of physical activity, air pollution (PM2·5and NO2) and injury for the New Zealand population from 2018 to 2050. We modelled impacts for Māori (the Indigenous Peoples of Aotearoa) and non-Māori.FindingsBoth pathways show improvements in population health, reductions in health system costs and reduced lifecycle greenhouse gas emissions compared to baseline, although health gains were substantially larger in the Behaviour pathway. Health gains were 20-30% larger for Māori than non-Māori in both pathways, although more healthy life years were gained by Māori in the Behaviour pathway. For those aged 0-4 in 2018, healthy life expectancy differences between Māori and non-Māori reduced by 0·5% in the Behaviour pathway. Healthy life years gained by Māori and non-Māori altered substantially depending on assumptions about the equity of the implemented pathway.InterpretationDecarbonising transport may reduce health and healthy life expectancy inequities between Māori and non-Māori if policies supporting decarbonisation are implemented equitably. Pathways that increase physical activity will have a much larger impact on population health than those which rely on low emission vehicles.Funding:Health Research Council of New Zealand (20/151) and University of Otago.
Yellow fever in Ghana: Predicting emergence and ecology from historical outbreaks
Authors: Judson Seth D. , Kenu Ernest , Fuller Trevon , Asiedu-Bekoe Franklin , Biritwum-Nyarko Alberta , Schroeder Lee F. , Dowdy David W. 
Published: January 2024

AbstractUnderstanding the epidemiology and ecology of yellow fever in endemic regions is critical for preventing future outbreaks. Ghana is a high-risk country for yellow fever. In this study we estimate the epidemiology, ecological cycles, and areas at risk for yellow fever in Ghana based on historical outbreaks. We identify 2371 cases and 887 deaths (case fatality rate 37.4%) from yellow fever reported in Ghana from 1910 to 2022. Since implementation of routine childhood vaccination in 1992, the estimated mean annual number of cases decreased by 81% and the geographic distribution of yellow fever cases also changed. While there have been multiple large historical outbreaks of yellow fever in Ghana from the urban cycle, recent outbreaks have originated among unvaccinated nomadic groups in rural areas with the sylvatic/savanna cycles. Using machine learning and an ecological niche modeling framework, we predict areas in Ghana that are similar to where prior yellow fever outbreaks have originated based on temperature, precipitation, landcover, elevation, and human population density. We find differences in predictions depending on the ecological cycles of outbreaks. Ultimately, these findings and methods could be used to inform further subnational risk assessments for yellow fever in Ghana and other high-risk countries.Author SummaryYellow fever is a viral hemorrhagic fever transmitted by mosquitoes in Africa and South America through different ecological transmission cycles. While West Africa has had the most cases of yellow fever, less is known about the epidemiology and ecology of yellow fever among countries in this region. Ghana has had multiple yellow fever outbreaks, including a recent outbreak in 2021-2022. In this study we estimate cases and deaths due to yellow fever in Ghana, compare the ecological cycles of outbreaks, and predict future areas at risk based on prior yellow fever cases and environmental conditions. We find that the populations at risk for yellow fever in Ghana have changed over the past century and that different ecological factors influence the risk of future emergence. Understanding these changes and the nuances of yellow fever epidemiology and ecology within countries will be important for future outbreak preparedness.
Discovering additional genetic loci associated with six psychiatric disorders/traitsviaFDR regression model leveraging external genetic and biological data
Authors: Rao Shi-tao , Qiu Jing-hong , Zhi Yi-qiang , Lin Yu-ping , Zhang Ruo-yu , Chen Xiao-tong , Xu Dan , So Hon-Cheong 
Published: January 2024

AbstractBackgroundCommon psychiatric disorders have substantial heritability influenced by multiple genes. While a number of susceptibility variants have been identified, many associated variants remain undiscovered. This study aimed to identify additional genetic loci associated with common psychiatric disorders/traits by leveraging correlated traits and biological annotations.MethodsWe proposed application of the false discovery rate (FDR) regression model to uncover additional genetic loci for six psychiatric disorders/traits. To enhance the likelihood of discovering additional significant genetic loci and genes, we utilized a set of 42 correlated traits and 21 biological annotations as covariates. Internal validation analysis and drug cluster enrichment analysis were conducted to validate the biological significance of the additional genetic loci/genes uncovered. We also experimentally validated two additional genes revealed for autism spectrum disorder (ASD).ResultsThe FDR regression (FDRreg) analysis strategy revealed hundreds of additional significant genes (FDR<0.01) in gene-level analyses, surpassing the number of significant genes found in the original studies. Specifically, in 11/16 trait analyses, FDRreg identified more significant genes based on gene-based analysis with MAGMA, and in 12/16 analyses, FDRreg identified more significant genes based on imputed expression in the brain. In SNP-level results, the majority of analyses (13/16) identified an equal or higher number of genomic risk loci (FDR<0.01). We found that FDRreg is able to reveal genes that are later known to be significant in subsequent larger-scale GWAS. Drug cluster enrichment analysis demonstrated a stronger enrichment in psychiatry-related drug clusters. In utero electroporation (IUE) experiments provided evidence to support two additional genes identified for ASD in critical embryonic brain development processes.ConclusionsBy integrating genetically correlated traits and biological annotations, the FDRreg strategy enables the identification of a greater number of additional significant genes and risk loci. Moreover, the new associated genes exhibited meaningful biological and clinical implications. This study presents a valuable approach for uncovering the genetic basis of psychiatric disorders and gaining insights into their underlying biology.
Reliability of single-lead electrocardiogram interpretation to detect atrial fibrillation: insights from the SAFER Feasibility Study
Authors: Hibbitt Katie , Brimicombe James , Cowie Martin R. , Dymond Andrew , Freedman Ben , Griffin Simon J , Hobbs FD Richard , Lindén Hannah Clair , Lip Gregory Y. H. , Mant Jonathan , McManus Richard J. , Pandiaraja Madhumitha , Williams Kate , Charlton Peter H. 
Published: January 2024

AbstractBackground and AimsSingle-lead electrocardiograms (ECGs) can be recorded using widely available devices such as smartwatches and handheld ECG recorders. Such devices have been approved for atrial fibrillation (AF) detection. However, little evidence exists on the reliability of single-lead ECG interpretation. We aimed to assess the level of agreement on detection of AF by independent cardiologists interpreting single lead ECGs, and to identify factors influencing agreement.MethodsIn a population-based AF screening study, adults aged ≥65 years old recorded four single-lead ECGs per day for 1-4 weeks using a handheld ECG recorder. ECGs showing signs of possible AF were identified by a nurse, aided by an automated algorithm. These were reviewed by two independent cardiologists who assigned participant- and ECG-level diagnoses. Inter-rater reliability of AF diagnosis was calculated using linear weighted Cohen’s kappa (κw).ResultsOut of 2,141 participants and 162,515 ECGs, only 1,843 ECGs from 185 participants were reviewed by both cardiologists. Agreement was moderate:κw= 0.42 (95% CI, 0.32 – 0.52) at participant-level; andκw= 0.51 (0.46 – 0.56) at ECG-level. At participant-level, agreement was associated with the number of adequate-quality ECGs recorded, with higher agreement in participants who recorded at least 67 adequate-quality ECGs. At ECG-level, agreement was associated with ECG quality and whether ECGs exhibited algorithm-identified possible AF.ConclusionInter-rater reliability of AF diagnosis from single-lead ECGs was found to be moderate in older adults. Strategies to improve reliability might include participant and cardiologist training and designing AF detection programmes to obtain sufficient ECGs for reliable diagnoses.What’s NewWe observed moderate agreement between cardiologists when diagnosing AF from single-lead ECGs in an AF screening study.This study indicates that for every 100 screening participants diagnosed with AF by two cardiologists, there would be complete disagreement over the diagnosis of 70 further participants.We found that the quality of ECG signals greatly influenced the reliability of single-lead ECG interpretation.In addition, when multiple ECGs were acquired from an individual, the reliability of participant-level diagnoses was influenced by the number of adequate-quality ECGs available for interpretation.
Quality measures of two-stage newborn hearing screening: Systematic review with a Bayesian meta-analysis
Authors: Manz Kirsi , Nennstiel Uta , Marzi Carola , Mansmann Ulrich , Brockow Inken 
Published: January 2024

AbstractBackgroundNewborn Screening for hearing impairment (NHS) is a crucial public health issue worldwide. Often, a two-stage screening with two different testing approaches is used. We aimed to investigate the optimal screening algorithm, based on data from the literature published in the last 30 years. A particular focus of the study was to synthesize the existing evidence on two-stage newborn hearing screening regarding the refer rate (RFR), the percentage of children that did not pass the second test or were lost after the first test.MethodsWe searched MEDLINE and Scopus for studies on two-stage NHS using transitory evoked otoacoustic emissions (TEOAE) or automated auditory brainstem response (AABR). All studies on newborns who received their first test as an inpatient and a second test up to one month later were eligible. Random effects meta-analysis and Bayesian modeling were performed to estimate RFR as well as effects of the second test phase on the RFR. Risk of bias was assessed using QUADAS-II. The unfunded study was registered in PROSPERO (CRD42023403091).ResultsEighty-five study protocols, including over 1,12 million newborns, met the inclusion criteria. Certainty in the evidence was rated as moderate. The RFR was higher when the test method was changed than without a change of method (AABR-AABR: RFR = 1.3% (95% confidence interval (CI): 0.9, 1.8%), TEOAE-TEOAE: RFR = 2.7% (CI: 2.2, 3.2%), TEOAE-AABR: RFR = 3.9% (CI: 2.9, 5.1%), AABR-TEOAE: 5.9% (CI: 5.0, 6.9%).ConclusionsStrategies that did not involve changes to the screening method had lower RFR.
Prevalence of Late-Stage Parkinson’s Disease in the US Health Care System: Insights from TriNetX
Authors: De Jesus Sol , Daya Annika , Blumberger Liba , Lewis Mechelle M. , Leslie Doug , Tabbal Samer D. , Dokholyan Rachel , Snyder Amanda M. , Mailman Richard B. , Huang Xuemei 
Published: January 2024

AbstractBackgroundPatients in late-stage Parkinson’s disease (PDLS) are caregiver dependent, have low quality of life, and higher health care costs.ObjectiveTo estimate the prevalence of PDLSpatients in the current United States (US) health care system.MethodsWe downloaded the 2010-2022 data from the TriNetX Diamond claims network that consists of 92 USA health care sites. PD was identified using standard diagnosis codes, and PDLSwas identified by the usage of wheelchair dependence, personal care assistance and/or presence of diagnoses of dementia. Age of PDLSidentification, and survival information are obtained and stratified by demographic and the disability subgroups.ResultsWe identified 1,031,377 PD patients in the TriNetX database. Of these, 18.8% fit our definition of PDLS(n=194,297), and 10.2% met two or more late-stage criteria. Among all PDLS, the mean age of PDLSidentification was 78.1 (±7.7), and 49% were already reported as deceased. PDLSpatients were predominantly male (58.5%), with similar distribution across PDLSsubgroups. The majority did not have race (71%) or ethnicity (69%) information, but for the available information, >90% (n=53,162) were white, 8.2% (n=5,121) Hispanic/Latino, 7.8% (n=4,557) black, and <0.01% (n=408) Asian. Of the PDLScohort, 71.6% identified with dementia, 12.9% had personal care assistance, and 4.8% were wheelchair bound.ConclusionsLate-stage patients are a significant part of PD landscape in the current US healthcare system, and largely missed by traditional motor-based disability staging. It is imperative to include this population as a clinical, social, and research priority.
Estimating the impact of transfluthrin-treated eave ribbons, Suna traps and their combination on malaria case incidence, based on semi-field and field data
Authors: Denz Adrian , Njoroge Margaret M. , Tambwe Mgeni M. , Kamber Lars , Cavelan Aurélien , Smith Thomas A. , van Loon Joop J.A. , Hiscox Alexandra , Saddler Adam , Fillinger Ulrike , Moore Sarah J. , Chitnis Nakul 
Published: January 2024

ABSTRACTGlobal malaria incidence has been reduced drastically since the year 2000, primarily due to the widespread use of insecticide-treated nets (ITNs), which kill the bloodfeedingAnophelesmosquitoes vectoring the disease in addition to protecting individuals sleeping under them from bites. However, progress has stalled since the mid-2010s and malaria continues to kill more than half a million people globally each year. New, complementary vector control tools are needed to further reduce the residual malaria transmission and face a potential decline in ITN effectiveness due to insecticide resistance. Transfluthrin-treated eave ribbons are a promising spatial repellent to protect people when they are in or around the house but not under an ITN, while the odour-baited Suna trap may present an insecticide-free means of killing mosquitoes. In previous semi-field and field studies, we assessed the effect of the eave ribbon, the Suna trap and the combined push-pull system on mosquito-human contact and mosquito mortality. Here, we combine this evidence and predict the malaria case incidence reduction if these interventions were deployed at a large scale in two East African transmission settings under full uncertainty quantification by use of a stochastic, individual-based simulation platform of malaria epidemiology. Our simulations suggest that the transfluthrin-treated eave ribbon may substantially reduce malaria case incidence in settings with low-transmission or with low ITN use, especially in regions whereAnopheles funestusdominates among malaria vectors and primarily uses human hosts. However, by diverting mosquitoes from indoor to outdoor host-search, the eave ribbon may reduce the community-protective killing effect of ITNs. In addition, people neither protected by an ITN nor the eave ribbon may experience an increase in malaria incidence at high but imperfect coverage with the eave ribbon. The Suna trap only showed a marginal effect on case incidence and the effect of the combined push-pull system was similar to the effect of the eave ribbon alone. Hence, the eave ribbon appears to be a promising tool in settings difficult to reach with ITNs, such as migrant agricultural workers, but deployment alongside ITNs needs to be planned with care, and ensuring the highest possible use of ITNs remains crucial.
Trade-off Between Resistance and Persistence in High Cell DensityEscherichia ColiCultures
Authors: Beulig F. , Bafna-Rührer J. , Jensen P.E. , Kim S.H. , Patel A. , Kandasamy V. , Steffen C. S. , Decker K. , Zielinski D.C. , Yang L. , Özdemir E. , Sudarsan S. , Palsson B.O. 
Published: January 2024

AbstractMicrobes experience high cell density in many environments that come with diverse resource limitations and stresses. However, high density physiology remains poorly understood. We utilized well-controlled culturing systems to grow wild-type and metabolically engineeredEscherichia colistrains into high cell densities (50–80 g Cdry cell weightL-1) and determine the associated transcriptional dynamics. Knowledge-enriched machine-learning-based analytics reveal distinct stress-related gene expression patterns that are consistent with a fundamental trade-off between resistance and persistence. We suggest that this trade-off explains observed growth arrests in high-density cultures and that it results from the disruption of cellular homeostasis, due to reallocation of limited cellular resources from resistance functions towards maintenance requirements of engineered production pathways. This study deepens our understanding of high-density physiology and demonstrates its importance to fundamental biomanufacturing challenges.
Ataxia Telangiectasia patient-derived neuronal and brain organoid models reveal mitochondrial dysfunction and oxidative stress
Authors: Leeson Hannah C , Aguado Julio , Gómez-Inclán Cecilia , Chaggar Harman Kaur , Taherian Fard Atefah , Hunter Zoe , Lavin Martin F , Mackay-Sim Alan , Wolvetang Ernst J 
Published: January 2024

AbstractAtaxia Telangiectasia (AT) is a rare genetic disorder caused by mutations in theATMgene and is characterized by oxidative stress, premature ageing, and progressive neurodegeneration of the cerebellum. The molecular mechanisms driving the neurological defects AT remain unclear, mainly due to lack of human neuronal models. Here, we use AT patient-derived pluripotent stem cells (iPSCs) and iPSC-derived neurons and brain organoids to comprehensively explore mitochondrial dysfunction, oxidative stress, and senescence phenotypes. We identified mislocalisation of mitochondria, a prevailing reduction in mitochondrial membrane potential, and increased oxidative stress in AT patient-derived iPSC and neuronal cultures that was restored by ATM gene correction. Cortical brain organoids from AT patients also display extensive oxidative stress, increased levels of senescence, and impaired neuronal function that could be counteracted with antioxidant treatment. Transcriptomic analysis identified disruptions in regulatory networks related to mitochondrial function and maintenance, including alterations in the PARP/SIRT signalling axis and dysregulation of key mitophagy and mitochondrial fission-fusion processes. Our study reveals that progressive mitochondrial dysfunction and aberrant ROS production are hallmarks of AT, and lead us to conclude that ATM is a master regulator of mitochondrial homeostasis.
Xylan inhibition of cellulase binding and processivity observed at single-molecule resolution
Authors: Zexer Nerya , Paradiso Alec , Nong Daguan , Haviland Zachary K. , Hancock William O. , Anderson Charles T. 
Published: January 2024

AbstractEfficient cellulose degradation by cellulase enzymes is crucial for using lignocellulosic biomass in bioenergy production. In the cell wall of plants, cellulose is bound by lignin and hemicellulose, which are key factors contributing to the recalcitrance of plant biomass. These non-cellulosic cell wall components are known to interfere with the function of cellulolytic enzymes. While the effects of lignin have been studied extensively, the contribution of xylan, the major hemicellulose in the secondary cell walls of plants, is often overlooked. To study those effects, we generated model cell wall composites by growing bacterial cellulose supplemented with varying concentrations of purified xylan. We used single-molecule microscopy to image and track fluorescently labeledTrCel7A, a commonly used model cellulase, as it binds and hydrolyses cellulose in these synthetic composites. We found that minute amounts of xylan are sufficient to significantly inhibit the binding of Cel7A to cellulose. The inclusion of xylan also reduced considerably the proportion of moving enzyme molecules, without affecting their velocity and run length. We suggest that, when available at low concentrations, xylan thinly coats cellulose fibrils, and incorporates as continuous patches when available at higher concentrations. Non-productive binding of Cel7A to xylan was not found to be a major inhibition mechanism. Our results highlight the importance of targeting xylan removal during biomass processing and demonstrate the potential of using single-molecule imagining to study the activity and limitations of cellulolytic enzymes.Graphical abstract