bluuebunny/crossref_metadata_2025_split huggingface dataset:
The economic burden of RSV-associated illness in children aged <5 years, South Africa 2011-2016
Authors: Moyes Jocelyn , Tempia Stefano , Walaza Sibongile , McMorrow Meredith L. , Treurnicht Florette , Wolter Nicole , von Gottberg Anne , Kahn Kathleen , Cohen Adam L , Dawood Halima , Variava Ebrahim , Cohen Cheryl 
Published: June 2022

AbstractIntroductionData on the economic burden of RSV-associated illness will inform decisions on the programmatic implementation of maternal vaccines and monoclonal antibodies. We estimated these costs in fine age bands to allow more accurate cost-effectiveness models to account for limited duration of protection conferred by short or long acting interventions.MethodsWe conducted a costing study at sentinel sites across South Africa to estimate out-of-pocket and indirect costs for RSV-associated mild and severe illness. We collected facility-specific costs for staffing, equipment, services, diagnostic tests and treatment. Using case-based data we calculated a patient day equivalent (PDE) for RSV-associated hospitalisations or clinic visits; the PDE was multiplied by the number of days of care to provide a case-cost to the healthcare system. We estimated the costs in 3-month age intervals in children aged <1 years and as a single group for children aged 1-4 years. We then applied our data to a modified version of the World Health Organization tool for estimating mean annual national cost burden, including medically and non-medically attended RSV-associated illness.ResultsThe estimated mean annual cost of RSV-associated Illness in children aged <5 years was United States dollars ($)137 204 393, of which 81% ($111 742 713) were healthcare system incurred, 6% ($8 881 612) were out of pocket expenses and 13% ($28 225 801) were indirect costs. Thirty-three percent ($45 652 677/$137 204 393) of the total cost in children aged <5 years was in the <3-month age group, of which 52% ($71 654 002) were healthcare system incurred. The costs of non-medically attended cases increased with age from $3 307 218 in the <3-month age group to $8 603 377 in the 9-11-month age group.ConclusionAmong children <5 years of age with RSV in South Africa, the highest cost burden was in young infants; therefore, interventions against RSV targeting this age group are important to reduce the health and cost burden of RSV-associated illness.
A mechanistic model explains oscillatory slowing and neuronal hyperactivity in Alzheimer’s disease
Authors: Alexandersen Christoffer G. , de Haan Willem , Bick Christian , Goriely Alain 
Published: June 2022

AbstractAlzheimer’s disease is the most common cause of dementia and is linked to the spreading of pathological amyloid-β and tau proteins throughout the brain. Recent studies have highlighted stark differences in how amyloid-β and tau affect neurons at the cellular scale. On a larger scale, Alzheimer’s patients are observed to undergo a period of early-stage neuronal hyperactivation followed by neurodegeneration and frequency-slowing of neuronal oscillations. Herein, we model the spreading of both amyloid-β and tau across a human connectome and investigate how the neuronal dynamics are affected by disease progression. By including the effects of both amyloid-β and tau pathology, we find that our model explains AD-related frequency slowing, early-stage hyperactivation, and late-stage hypoactivation. By testing different hypotheses, we show that hyperactivation and frequency-slowing are not due to the topological interactions between different regions but are mostly the result of local neurotoxicity induced by amyloid-β and tau protein.
Applications of a Novel Reciprocating Positive Displacement Pump in the Simulation of Pulsatile Arterial Blood Flow
Authors: Menkara Adam , Faryami Ahmad , Viar Daniel , Harris Carolyn A 
Published: June 2022

AbstractPulsatile arterial blood flow plays an important role in vascular system mechanobiology, especially in the study of mechanisms of pathology. Limitations in cost, setup time, sample size, and control across current in-vitro and in-vivo methods prevent future exploration of novel treatments. Presented is the verification of a novel reciprocating positive displacement pump aimed at resolving these issues through the simulation of human ocular, human fingertip and skin surface, human cerebral, and rodent spleen organ systems. A range of pulsatile amplitudes, frequencies, and flow rates were simulated using pumps made of 3D printed parts incorporating a tubing system, check valve and proprietary software. Volumetric analysis of 430 total readings across a flow range of 0.025ml/min to 16ml/min determined that the pump had a mean absolute error and mean relative error of 0.041 ml/min and 1.385%, respectively. Linear regression of flow rate ranges yielded R2 between 0.9987 and 0.9998. Waveform analysis indicated that the pump could recreate accurate beat frequency for flow ranges above 0.06ml/min at 70BPM. The verification of accurate pump output opens avenues for the development of novel long-term in-vitro benchtop models capable of looking at fluid flow scenarios previously unfeasible, including low volume-high shear rate pulsatile flow.
Autophagy degrades myelin proteins and is essential for maintaining CNS myelin homeostasis
Authors: Ktena Niki , Kaplanis Stefanos Ioannis , Kolotuev Irina , Georgilis Alexandros , Stavroulaki Vasiliki , Kallergi Emmanouela , Nikoletopoulou Vassiliki , Karagogeos Domna , Savvaki Maria 
Published: June 2022

Abstract(Macro)autophagy comprises a major lysosome-dependent degradation mechanism which engulfs, removes and recycles unwanted cytoplasmic material, including damaged organelles and toxic protein aggregates. Although a few studies implicate autophagy in CNS demyelinating pathologies, its role, particularly in mature oligodendrocytes and CNS myelin, remains poorly studied. Here, using both pharmacological and genetic inhibition of the autophagic machinery, we provide evidence that autophagy is an essential mechanism for oligodendrocyte maturation in vitro. Our study reveals that two core myelin proteins, namely proteolipid protein (PLP) and myelin basic protein (MBP) are incorporated into autophagosomes in oligodendrocytes, resulting in their degradation. Furthermore, we ablated atg5, a core gene of the autophagic machinery, specifically in myelinating glial cells in vivo by tamoxifen administration (plp-CreERT2; atg5F/F) and showed that myelin maintenance is perturbed, leading to PLP accumulation. Significant morphological defects in myelin membrane such as decompaction accompanied with increased axonal degeneration are observed. As a result, the mice exhibit behavioral deficits. In summary, our data highlight that the maintenance of adult myelin homeostasis in the CNS requires the involvement of a fully functional autophagic machinery.
Theropod dinosaurs had primate-like numbers of telencephalic neurons
Authors: Herculano-Houzel Suzana 
Published: June 2022

AbstractUnderstanding the neuronal composition of the brains of dinosaurs and other fossil amniotes would offer fundamental insight into their behavioral and cognitive capabilities, but brain tissue is only rarely fossilized. However, when the bony brain case is preserved, the volume and therefore mass of the brain can be estimated with computer tomography; and if the scaling relationship between brain mass and numbers of neurons for the clade is known, that relationship can be applied to estimate the neuronal composition of the brain. Using a recently published database of numbers of neurons in the telencephalon of extant sauropsids (birds, squamates and testudines), here I show that the neuronal scaling rules that apply to these animals can be used to infer the numbers of neurons that composed the telencephalon of dinosaur, pterosaur and other fossil sauropsid species. The key to inferring numbers of telencephalic neurons in these species is first using the relationship between their estimated brain and body mass to determine whether bird-like (endothermic) or squamate-like (ectothermic) rules apply to each fossil sauropsid species. This procedure shows that the notion of “mesothermy” in dinosaurs is an artifact due to the mixing of animals with bird-like and squamate-like scaling, and indicates that theropods such asTyrannosaurusandAllosauruswere endotherms with baboon- and monkey-like numbers of telencephalic neurons, respectively, which would make these animals not only giant but also long-lived and endowed with flexible cognition, and thus even more magnificent predators than previously thought.
Psychophysics with R: The R Package MixedPsy
Authors: Balestrucci Priscilla , Ernst Marc O. , Moscatelli Alessandro 
Published: June 2022

AbstractPsychophysical methods are widely used in neuroscience to investigate the quantitative relation between a physical property of the world and its perceptual representation provided by the senses. Recent studies introduced the Generalized Linear Mixed Model (GLMM) to fit the responses of multiple participants in psychophysical experiments. Another approach (two-level approach) requires fitting psychometric functions to each individual participant data using a Generalized Linear Model (GLM), and then testing the hypotheses on the multiple participants by means of a second level analysis. For either options, the implementation of the statistical analysis in R is possible and beneficial. Here, we introduce the package MixedPsy to model and fit psychometric data in R, either with two-level and GLMM approaches. The package, freely available in the CRAN repository, uses different methods for the estimation of Point of Subjective Equivalence (PSE) and Just Noticeable Difference (JND), and provides utilities for immediate visualization and plotting of the fitted results. This manuscript aims to provide researchers with a practical tutorial for implementing a complete analysis pipeline for psychophysical data using MixedPsy and other packages and basic functionalities of the R programming environment.
Extensive topographic remapping and functional sharpening in the adult rat visual pathway upon first visual experience
Authors: Carvalho Joana , Fernandes Francisca F. , Shemesh Noam 
Published: June 2022

AbstractUnderstanding the dynamics of stability/plasticity balances during adulthood is pivotal for learning, disease, and recovery from injury. However, the brain-wide topography of sensory remapping remains unknown. Here, using a first-of-its-kind setup for delivering patterned visual stimuli in a rodent Magnetic Resonance Imaging (MRI) scanner, coupled with biologically-inspired computational models, we noninvasively mapped brain-wide properties - receptive fields (RFs) and spatial frequency (SF) tuning curves - that were insofar only available from invasive electrophysiology or optical imaging. We then tracked the RF dynamics in the chronic Visual Deprivation Model (VDM) of plasticity, and found that light exposure progressively promoted a large-scale topographic remapping in adult rats. Upon light exposure, the initially unspecialized visual pathway progressively evidenced sharpened RFs (smaller and more spatially selective) and enhanced spatial frequency tuning curves. Our findings reveal that visual experience following VDM reshapes both structure and function of the visual system and shifts the stability/plasticity balance in adults.
Synthetic Coolant WS-23 increases E-Cigarette Generated Aerosolized Acellular Reactive Oxygen Species (ROS) Levels
Authors: Yogeswaran Shaiesh , Manevski Marko , Chand Hitendra S. , Rahman Irfan 
Published: June 2022

AbstractThere has been a substantial rise in e-cigarette (e-cig) use or vaping in the past decade, prompting growing concerns about their adverse health effects. Recently, e-cig manufacturers have been using synthetic cooling agents, like WS-23 and WS-3, to provide a cooling sensation without the “menthol taste”. Studies have shown that aerosols/vapes generated by e-cigs can contain significant levels of reactive oxygen species (ROS). However, studies investigating the role of synthetic coolants in modulating ROS levels generated by e-cigs are lacking. This study seeks to understand the potential of synthetic coolants, e-cigarette additives that have become increasingly prevalent in e-liquids sold in the United States (US), on acellular ROS production. Aerosols were generated from e-liquids with and without synthetic coolants through a single-puff aerosol generator; subsequently, acellular ROS was semi-quantified in H2O2 equivalents via fluorescence spectroscopy. Our data suggest that adding WS-3 to e-liquid base (PG:VG), regardless of nicotine content, has a minimal impact on modifying e-cigarette-generated acellular ROS levels. Additionally, our data also suggest that the addition of WS-23 to nicotine-containing e-liquid base significantly modifies e-cigarette-generated acellular ROS levels. Together, our data provide insight into whether adding synthetic coolants to e-liquids significantly impacts vaping-induced oxidative stress in the lungs.
The impact of lag time to cancer diagnosis and treatment on clinical outcomes prior to the COVID-19 pandemic: a scoping review of systematic reviews and meta-analyses
Authors: Tope Parker , Farah Eliya , Ali Rami , El-Zein Mariam , Miller Wilson H. , Franco Eduardo L. 
Published: June 2022

ABSTRACTBackgroundThe COVID-19 pandemic has disrupted cancer care, raising concerns regarding the impact of wait time, or ‘lag time’, on clinical outcomes. We aimed to contextualize pandemic-related lag times by mapping pre-pandemic evidence from systematic reviews and/or meta-analyses on the association between lag time to cancer diagnosis and treatment with mortality- and morbidity-related outcomes.MethodsWe systematically searched MEDLINE, EMBASE, Web of Science, and Cochrane Library of Systematic Reviews for reviews published prior to the pandemic (1 January 2010-31 December 2019). We extracted data on methodological characteristics, lag time interval start and endpoints, qualitative findings from systematic reviews, and pooled risk estimates of mortality-(i.e., overall survival) and morbidity- (i.e., local regional control) related outcomes from meta-analyses. We categorized lag times according to milestones across the cancer care continuum and summarized outcomes by cancer site and lag time interval.ResultsWe identified 9,032 records through database searches, of which 29 were eligible. We classified 33 unique types of lag time intervals across 10 cancer sites, of which breast, colorectal, head and neck, and ovarian cancers were investigated most. Two systematic reviews investigating lag time to diagnosis reported contradictory findings regarding survival outcomes among pediatric patients with Ewing’s sarcomas or central nervous system tumours. Comparable risk estimates of mortality were found for lag time intervals from surgery to adjuvant chemotherapy for breast, colorectal, and ovarian cancers. Risk estimates of pathologic complete response indicated an optimal time window of 7-8 weeks for neoadjuvant chemotherapy completion prior to surgery for rectal cancers. In comparing methods across meta-analyses on the same cancer sites, lag times, and outcomes, we identified critical variations in lag time research design.ConclusionsOur review highlighted measured associations between lag time and cancer-related outcomes and identified the need for a standardized methodological approach in areas such as lag time definitions and accounting for the waiting-time paradox. Prioritization of lag time research is integral for revised cancer care guidelines under pandemic contingency and assessing the pandemic’s long-term effect on patients with cancer.
Persistence of SARS-CoV-2 omicron variant in children and utility of rapid antigen testing as an indicator of culturable virus
Authors: Lohse Zoe M. , Shapiro Jerne J. , Lednicky John A. , Cash Melanie N. , Jun Inyoung , Mavian Carla N. , Tagliamonte Massimiliano S. , Saleem Cyrus , Yang Yang , Nelson Eric J. , Salemi Marco , Ryan Kathleen A. , Morris J. Glenn 
Published: June 2022

ABSTRACTWe screened 65 longitudinally-collected nasal swab samples from 31 children aged 0-16 years who were positive for SARS-CoV-2 omicron BA.1. By day 7 after onset of symptoms 48% of children remained positive by rapid antigen test. In a sample subset we found 100% correlation between antigen test results and virus culture.
Duration of protection after vaccination against yellow fever - systematic review and meta-analysis
Authors: Kling Kerstin , Domingo Cristina , Bogdan Christian , Duffy Steven , Harder Thomas , Howick Jeremy , Kleijnen Jos , McDermott Kevin , Wichmann Ole , Wilder-Smith Annelies , Wolff Robert 
Published: June 2022

AbstractBackgroundThe duration of protection after a single dose of yellow fever vaccine is a matter of debate. To summarize the current knowledge, we performed a systematic literature review and meta-analysis.MethodsStudies on the duration of protection after 1 and ≥2 vaccine doses were reviewed. Data were stratified by time since vaccination. In our meta-analysis, we used random-effects models.ResultsWe identified 36 studies from 20 countries, comprising over 17,000 participants aged 6 months to 85 years. Among healthy adults and children, pooled seroprotection rates after single vaccination dose were close to 100% by 3 months and remained high in adults for 5 to 10 years. In children vaccinated before age 2, the seroprotection rate was 52% within 5 years after primary vaccination. For immunodeficient persons, data indicate relevant waning.ConclusionsThe extent of waning of seroprotection after yellow fever vaccination depends on age at vaccination and immune status.SummarySystematic Review and meta-analysis of existing studies indicates a relevant waning of seroprotection after a single dose of yellow fever vaccination of different groups including healthy adults, children when vaccinated before the age of 2 years and immunodeficient persons.
Effects of the COVID-19 pandemic on self-reported 12-month pneumococcal vaccination series completion rates in Canada: An interrupted time-series analysis
Authors: Atkinson Katherine M , Ntacyabukura Blaise , Hawken Steven , Laflamme Lucie , Wilson Kumanan 
Published: June 2022

AbstractBackgroundRoutine childhood vaccination improves health and prevents morbidity and mortality from vaccination preventable diseases. There are indications that the COVID-19 pandemic has negatively impacted vaccination rates globally, but systematic studies on this are still lacking in Canada. This study aims to add knowledge on the effect of the pandemic on pneumococcal vaccination rates of children using self-reported immunization data entered into the CANImmunize digital vaccination tool.MethodologyAn interrupted time series analysis was conducted on aggregated monthly enrollment of children on the platform (2016-2021) and their pneumococcal immunization series completion rates (2016-2020). Predicted trends before and after the onset of the COVID-19 related restriction (March 1, 2020) were compared by means of an Autoregressive Integrated Moving Average (ARIMA).ResultsPandemic restrictions were associated with changes in self-reported pneumococcal immunization rates amongst the users of the CANImmunize platform. The monthly enrollment of children on the platform decreased by – 1177.52 records (95% CI: –1865.47, – 489.57), with a continued decrease of 80.84 records each month. Self-reported pneumococcal immunization series completion rates had an immediate increase of 14.57% (95% CI 4.64, 24.51) followed by a decrease of –3.54% each month.ConclusionThe onset of the COVID-19 related restrictions impacted enrollment of children in the CANImmunize digital immunization platform, and an overall decrease in self-reported pneumococcal immunization series completion rates. Our findings support that efforts to increase catch-up immunization campaigns so that children who could not get scheduled immunization during the pandemic are not missed.
Episomal editing of synthetic constructs in yeast using CRISPR
Authors: Zhao Yu , Coelho Camila , Lauer Stephanie , Laurent Jon M. , Brosh Ran , Boeke Jef D. 
Published: June 2022

AbstractUse of synthetic genomics to design and build “big” DNA has revolutionized our ability to answer fundamental biological questions by employing a bottom-up approach. S. cerevisiae, or budding yeast, has become the major platform to assemble large synthetic constructs thanks to its powerful homologous recombination machinery and the availability of well-established molecular biology techniques. However, efficiently and precisely introducing designer variations to episomal assemblies remains challenging. Here, we describe CRISPR Engineering of EPisomes in Yeast, or CREEPY, for rapid engineering of mammalian DNA constructs larger than 100 kb. We demonstrate that editing of circular episomes presents unique challenges compared to modifying native yeast chromosomes with CRISPR. After optimizing CREEPY for episomal editing, we achieve efficient simplex and multiplex editing as demonstrated by engineering a mouse Sox2-harboring episome.
Srsf2P95H/+ co-operates with loss of TET2 to promote myeloid bias and initiate a chronic myelomonocytic leukemia like disease in mice
Authors: Xu Jane Jialu , Chalk Alistair M. , Wall Meaghan , Langdon Wallace Y. , Smeets Monique F. , Walkley Carl R. 
Published: June 2022

AbstractRecurrent mutations in two pathways - the RNA spliceosome (eg. SRSF2, SF3B1, U2AF1) and epigenetic regulators (eg. DNMT3, TET2) – contribute to the development of myelodysplastic syndrome (MDS) and related myeloid neoplasms. In chronic myelomonocytic leukemia (CMML), SRSF2 mutations occur in ∼50% of patients and TET2 mutations in ∼60%, representing two of the most frequent mutations in these cancers. Clonal analysis has indicated that either mutation can arise as the founder lesion, however, our understanding of the basis for the co-operativity of these mutations in the evolution of CMML is limited. Based on human cancer genetics we crossed an inducible Srsf2P95H/+ mutant model with Tet2fl/fl mice to mutate both concomitantly (or individually) in hematopoietic stem cells. At 20-24 weeks post gene mutation, we observed subtle differences in the Srsf2/Tet2 mutants compared to either single mutant. Under conditions of native hematopoiesis with aging, we see a distinct myeloid bias and monocytosis in the Srsf2/Tet2 mutants. A subset of the compound Srsf2/Tet2 mutants display an increased granulocytic and distinctive monocytic proliferation (myelo-monocytic hyperplasia), with increased immature promonocytes and monoblasts (∼10-15% total nucleated cells), and evidence of binucleate promonocytes. Exome analysis of progressed disease demonstrates mutations in genes and pathways similar to those reported in human CMML. Upon transplantation, recipients developed leukocytosis, monocytosis and splenomegaly. This demonstrates we can reproduce Srsf2/Tet2 co-operativity in vivo, yielding a disease with core characteristics of CMML, unlike single Srsf2 or Tet2 mutation. This model represents a significant step toward building high fidelity and genetically tractable models of CMML.Key pointsSrsf2P95H/+ co-operates with Tet2-/- to initiate CMML in a murine modelSrsf2P95H and Tet2 null mutations synergize in the development of monocytosis