bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk of Coronavirus Disease 2019 (COVID-19) among Those Up-to-Date and Not Up-to-Date on COVID-19 Vaccination by US CDC Criteria
Authors: Shrestha Nabin K. , Burke Patrick C. , Nowacki Amy S. , Gordon Steven M. 
Published: June 2023

ABSTRACTBackgroundThe CDC recently defined being “up-to-date” on COVID-19 vaccination as having received at least one dose of a COVID-19 bivalent vaccine. The purpose of this study was to compare the risk of COVID-19 among those “up-to-date” and “not up-to-date”.MethodsEmployees of Cleveland Clinic in Ohio, USA, in employment when the COVID-19 bivalent vaccine first became available, and still employed when the XBB lineages became dominant, were included. Cumulative incidence of COVID-19 since the XBB lineages became dominant was compared across the ”up-to-date” and “not up-to-date” states, by treating COVID-19 bivalent vaccination as a time- dependent covariate whose value changed on receipt of the vaccine. Risk of COVID-19 by vaccination status was also evaluated using multivariable Cox proportional hazards regression adjusting for propensity to get tested for COVID-19, age, sex, most recent prior SARS-CoV-2 infection, and number of prior vaccine doses.ResultsCOVID-19 occurred in 1475 (3%) of 48 344 employees during the 100-day study period. The cumulative incidence of COVID-19 was lower in the “not up-to-date” than the “up-to-date” state. On multivariable analysis, being “up-to-date” was not associated with lower risk of COVID-19 (HR, 1.05; 95% C.I., 0.88-1.25;P-value, 0.58). Results were very similar when those 65 years and older were only considered “up-to-date” after 2 doses of the bivalent vaccine.ConclusionsSince the XBB lineages became dominant, adults “up-to-date” on COVID-19 vaccination by the CDC definition do not have a lower risk of COVID-19 than those “not up-to-date”, bringing into question the value of this risk classification definition.SummaryAmong 48 344 working-aged Cleveland Clinic employees, those “up-to-date” on COVID-19 vaccination did not have a lower risk of COVID-19 than those not “up-to-date”. The current CDC definition provides a meaningless classification of risk of COVID-19 in the adult population.
Evaluating the effects of supervised consumption sites on housing prices in Montreal, Canada using controlled interrupted time series and hedonic price models
Authors: Schaefer Maximilian , Panagiotoglou Dimitra 
Published: June 2023

AbstractBackgroundIn 2017, three brick and mortar supervised consumption sites (SCS) began operating in Montreal, Canada. Opponents argued the sites would attract people who use drugs to the respective neighbourhoods, contributing to reductions in residential real estate values.MethodsWe used controlled interrupted time series and hedonic price models to evaluate the effects of Montreal’s SCSs on residential real estate. We linked the Quebec Professional Association of Real Estate Brokers’ housing sales data provided by Centris Inc. with Statistics Canada’s census tract data, neighbourhood proximity measures, and Canadian Urban Environmental Health Research Consortium’s gentrification measures. We restricted analysis to sales between 1 January 2014 and 31 December 2021, and within 1,000m of a SCS (treated) or a men’s homeless shelter (control). We controlled for internal (e.g., number of bed/bathrooms, unit size) and external attributes (e.g., neighbourhood demographics; proximity to amenities), and included a spatio-temporal lag to account for correlation between sales.ResultsWhen controlling for census tract data and gentrification measures, the price of homes sold immediately after SCSs were implemented was 5.2% lower (95% CI: -1.4%, -8.8%) compared with control sales (level effect). However, the monthly value increased 0.6% faster (95% CI: 0.4%, 0.7%) in treated neighbourhoods (trend effect). Compared with the counterfactual (i.e., SCS never implemented), sales in treated neighbourhoods observed an absolute increase of $37,931.86 (95% CI: $12,223.35, $138,088.50) by December 2021. When we also controlled for proximity scores, the immediate level effect post-implementation disappeared (−3.3%, 95% CI: -0.7%, 1.1%), but monthly trend gains persisted (0.9%, 95% CI: 0.7%, 1.0%).ConclusionWe observed a modest negative effect on prices immediately following SCS implementation. However, controlling for proximity to neighbourhood amenities eliminated the level effect. Positive month-on-month price gains were consistently observed, suggesting community wide benefits of SCS implementation.
Metabolomic and genomic prediction of common diseases in 477,706 participants in three national biobanks
Authors:   Nightingale Health Biobank Collaborative Group, Barrett Jeffrey C. , Esko Tõnu , Fischer Krista , Jostins-Dean Luke , Jousilahti Pekka , Julkunen Heli , Jääskeläinen Tuija , Kerimov Nurlan , Kerminen Sini , Kolde Anastassia , Koskela Harri , Kronberg Jaanika , Lundgren Sara N. , Lundqvist Annamari , Mäkelä Valtteri , Nybo Kristian , Perola Markus , Salomaa Veikko , Schut Kirsten , Soikkeli Maiju , Soininen Pasi , Tiainen Mika , Tillmann Taavi , Würtz Peter ,   the Estonian Biobank Research Team
Published: June 2023

AbstractIdentifying individuals at high risk of chronic diseases via easily measured biomarkers could improve public health efforts to prevent avoidable illness and death. Here we present nuclear magnetic resonance blood metabolomics from half a million samples from three national biobanks. We built metabolomic risk scores that identify a high-risk group for each of 12 diseases that cause the most morbidity in high-income countries and show consistent cross-biobank replication of the relative risk of disease for these groups. We show that these metabolomic risk scores are more strongly associated with future disease onset than polygenic scores for most of these diseases. In a subset of 18,000 individuals with metabolomic biomarkers measured at two time points we show that people whose scores change have dramatically different future risk of disease, suggesting that repeat measurements capture the benefits of lifestyle change. We show cross-biobank calibration of our scores. Since metabolomics can be measured from a standard blood sample, we propose such tests can be feasibly implemented today in preventative health programs.One-Sentence SummaryBiomarkers from half a million blood samples identifies people at increased risk of chronic diseases and can be used for early detection today.
Harmonization of Later-Life Cognitive Function Across National Contexts: Results from the Harmonized Cognitive Assessment Protocols (HCAPs)
Authors: Gross Alden L. , Li Chihua , Briceno Emily M. , Rentería Miguel Arce , Jones Richard N. , Langa Kenneth M. , Manly Jennifer J. , Nichols Emma L. , Weir David , Wong Rebeca , Berkman Lisa , Lee Jinkook , Kobayashi Lindsay C. 
Published: June 2023

AbstractBackgroundThe Harmonized Cognitive Assessment Protocol (HCAP) is an innovative instrument for cross-national comparisons of later-life cognitive function, yet its suitability across diverse populations is unknown. We aimed to harmonize general and domain-specific cognitive scores from HCAPs across six countries, and evaluate precision and criterion validity of the resulting harmonized scores.MethodsWe statistically harmonized general and domain-specific cognitive function across the six publicly available HCAP partner studies in the United States, England, India, Mexico, China, and South Africa (N=21,141). We used an item banking approach that leveraged common cognitive test items across studies and tests that were unique to studies, as identified by a multidisciplinary expert panel. We generated harmonized factor scores for general and domain- specific cognitive function using serially estimated graded-response item response theory (IRT) models. We evaluated precision of the factor scores using test information plots and criterion validity using age, gender, and educational attainment.FindingsIRT models of cognitive function in each country fit well. We compared measurement reliability of the harmonized general cognitive function factor across each cohort using test information plots; marginal reliability was high (r> 0·90) for 93% of respondents across six countries. In each country, general cognitive function scores were lower with older ages and higher with greater levels of educational attainment.InterpretationWe statistically harmonized cognitive function measures across six large, population-based studies of cognitive aging in the US, England, India, Mexico, China, and South Africa. Precision of the estimated scores was excellent. This work provides a foundation for international networks of researchers to make stronger inferences and direct comparisons of cross-national associations of risk factors for cognitive outcomes.FundingNational Institute on Aging (R01 AG070953, R01 AG030153, R01 AG051125, U01 AG058499; U24 AG065182; R01AG051158)
A frameshift variant in the melanophilin gene is associated with loss of pigment from shed skin in ball pythons (Python regius)
Authors: Lederer Izabella , Shahid Basmah , Dao Uyen M. , Brogdon Alex , Byrtus Hannah , Delva Marcelin , Deva Orson , Hatfield Paige , Hertz Mikayla , Justice Jenna , Mavor Sarah , Pilbeam Erin , Rice Zoe , Simpson Abbey , Temar Hallie , Wynn Richard , Xhangolli Joana , Graves Chiron W. , Seidel Hannah S. 
Published: June 2023

AbstractMelanophilin is a myosin adaptor required for transporting the pigment melanin within cells. Loss of melanophilin in fish, birds, and mammals causes pigmentation defects, but little is known about the role of melanophilin in non-avian reptiles. Here we show that a frameshift in the melanophilin gene in ball python (P. regius) is associated with loss of pigment from shed skin. This variant is predicted to remove the myosin-binding domain of melanophilin and thereby impair transport of melanin-containing organelles. Our study represents the first description of a melanophilin variant in a non-avian reptile and confirms the role of melanophilin across vertebrates.
Nuclear aging in polyglutamine-induced neurodegeneration
Authors: Pereira Dina , Cunha-Santos Janete , Vasconcelos-Ferreira Ana , Duarte-Neves Joana , Onofre Isabel , Carmona Vítor , Aveleira Célia A , Lopes Sara M , Lobo Diana D , Martins Inês M , Gonçalves Nélio , Cavadas Cláudia , Pereira de Almeida Luís 
Published: June 2023

AbstractMachado-Joseph disease (MJD) is an autosomal dominantly-inherited neurodegenerative disorder characterized by an over-repetition of the CAG trinucleotide of theATXN3gene, conferring a toxic gain-of-function to the resulting ataxin-3 protein. Despite the significant advances produced over the last years, the molecular mechanisms involved in MJD are still unclear and no treatment able to modify the disease progression is available. Aging is the major risk factor for neurodegenerative disorders, being associated with the occurrence and progression of several diseases, such as Alzheimer’s, Huntington’s, among others. The nuclear membrane proteins - lamins - and lamin-processing related proteins, such as ZMPSTE24, have been shown to be altered, not only during normal aging, but also in neurodegenerative disorders, such as Alzheimer’s disease.Taking this into account, we aimed at investigating the role of aging in MJD by evaluating the presence of age-related markers in human and animal MJD models. Decreased levels of lamins B and C, together with decreased ZMPSTE24 levels were identified in the different MJD models. Accordingly, abnormalities in nuclear circularity, a hallmark of aging, were also observed in a N2a MJD cellular model, supporting an age-related phenotype. Furthermore, overexpressing progerin, the abnormal lamin A, generated in Hutchinson Guilford Progeria Syndrome patients that present premature and accelerated aging, in a relevant brain area of a lentiviral MJD mouse model, induced an aggravation of MJD-associated neuropathology.Our results suggest that aging is a key player in the context of MJD pathogenesis, unveiling new pathways for the development of future therapies for the disease.
Increased dispersal explains increasing local diversity with global biodiversity declines
Authors: Fagan Brennen , Pitchford Jon W. , Stepney Susan , Thomas Chris D 
Published: June 2023

The narrative of biodiversity decline in response to human impacts is overly simplistic because different biodiversity metrics show different trajectories at different spatial scales. It is also debated whether human-caused biodiversity changes lead to subsequent, accelerating change (cascades) in ecological communities, or alternatively build increasingly robust community networks with decreasing extinction rates and reduced invasibility. Mechanistic approaches are needed that simultaneously reconcile different metrics of biodiversity change, and explore the robustness of communities to further change. We develop a trophically-structured, mainland-archipelago metacommunity model of community assembly. Varying the parameters across model simulations shows that local alpha diversity (the number of species per island) and regional gamma diversity (the total number of species in the archipelago) depend on both the rate of extirpation per island and on the rate of dispersal between islands within the archipelago. In particular, local diversity increases with increased dispersal and heterogeneity between islands, but regional diversity declines because the islands become biotically similar and local one-island and few-island species are excluded (homogenisation, or reduced beta diversity). This mirrors changes observed empirically: real islands have gained species (increased local and island-scale community diversity) with increased human-assisted transfers of species, but global diversity has declined with the loss of endemic species. However, biological invasions may be self-limiting. High-dispersal, high local-diversity model communities become resistant to subsequent invasions, generating robust species-community networks unless dispersal is extremely high. A mixed-up world is likely to lose many species, but the resulting ecological communities may nonetheless be relatively robust.Significance StatementBiodiversity is commonly regarded as threatened due to human impacts, but biodiversity metrics at different scales produce contradictory results. A framework is needed that can reproduce and connect these results across scales and address whether biodiversity change will inexorably accelerate following perturbation or become self-limiting as new ecological communities form. We address this challenge by constructing size-structured model communities using a mainland/island paradigm and tracking diversity at different scales. Our simulations reproduce the literature’s discrepancy across scales and provide new insight. Ecological communities (islands) gain species with increasing (human-assisted) dispersal, but global diversity declines with the consequent loss of endemic species. Communities also become less invasible as dispersal increases, suggesting that human-mediated dispersal favours robust communities that resist subsequent change.
Ketogenic diet as a metabolic vehicle for enhancing the therapeutic efficacy of mebendazole and devimistat in preclinical pediatric glioma
Authors: Mukherjee Purna , Greenwood Bennett , Henao Juan , Kiebish Michael A. , Seyfried Thomas N. 
Published: June 2023

AbstractInvasion of high-grade glioma (HGG) cells through the brain and spinal cord is a leading cause of cancer death in children. Despite advances in treatment, survivors often suffer from life-long adverse effects of the toxic therapies. This study investigated the influence of nutritional ketosis on the therapeutic action of mebendazole (MBZ) and devimistat (CPI-613) against the highly invasive VM-M3 glioblastoma cells in juvenile syngeneic p20-p25 mice; a preclinical model of pediatric HGG. Cerebral implantation of the VM-M3 glioblastoma cells invaded throughout the brain and the spinal column similar to that seen commonly in children with malignant glioma. The maximum therapeutic benefit of MBZ and CPI-613 on tumour invasion and mouse survival occurred only when the drugs were administered together with a ketogenic diet (KD). MBZ reduced VM-M3 tumour cell growth and invasion when evaluated underin-vitroandin-vivoconditions through inhibition of both the glutaminolysis and the glycolysis pathways.Moreover, administration of the drugs with the KD allowed a low dosing for the juvenile mice, which minimized toxicity while improving overall survival. This preclinical study in juvenile mice highlights the potential importance of a diet/drug therapeutic strategy for managing childhood brain cancer.
Gauge equivariant convolutional neural networks for diffusion mri
Authors: Hussain Uzair , Khan Ali R. 
Published: June 2023

AbstractDiffusion MRI (dMRI) is an imaging technique widely used in neuroimaging research, where the signal carries directional information of underlying neuronal fibres based on the diffusivity of water molecules. One of the shortcomings of dMRI is that numerous images, sampled at gradient directions on a sphere, must be acquired to achieve a reliable angular resolution for model-fitting, which translates to longer scan times, higher costs, and barriers to clinical adoption. In this work we introduce gauge equivariant convolutional neural network (gCNN) layers for dMRI that overcome the challenges associated with the signal being acquired on a sphere with antipodal points identified. This is done by noting that the domain is equivalent to the real projective plane, ℝP2, which is a non-euclidean and a non-orientable manifold. This is in stark contrast to a rectangular grid which typical convolutional neural networks (CNNs) are designed for. We apply our method to upsample angular resolution for predicting diffusion tensor imaging (DTI) parameters from just six diffusion gradient directions. The symmetries introduced allow gCNNs the ability to train with fewer subjects as compared to a baseline model that involves only 3D convolutions.
Parthenogenesis, sexual conflict, and selection on fertilization rates in switching environments
Authors: Liu Xiaoyuan , Pitchford Jon W. , Constable George W.A. 
Published: June 2023

AbstractIn the face of varying environments, organisms exhibit a variety of reproductive modes, from asexuality to obligate sexuality. Should reproduction be sexual, the morphology of the sex cells (gametes) produced by these organisms has important evolutionary implications; these cells can be the same size (isogamy), one larger and one smaller (anisogamy), and finally the larger cell can lose its capacity for motility (oogamy, the familiar sperm-egg system). Understanding the origin of the sexes, which lies in the types of gametes they produce, thus amounts to explaining these evolutionary transitions. Here we extend classic results in this area by exploring these transitions in a model in which organisms can reproduce both sexually and asexually (a reproductive mode present in many algae). In particular, we investigate the co-evolution of gamete cell size with fertilization rate, which is a proxy for motility and pheromone production but usually held constant in such models. Using adaptive dynamics generalized to the case of switching environments, we find that isogamy can evolve to anisogamy through evolutionary branching, and that anisogamy can evolve to oogamy or suppressed pheromone production through a further branching driven by sexual conflict. We also derive analytic conditions on the model parameters required to arrest evolution on this isogamy-oogamy trajectory, with low fertilization rates and stochastically switching environments stabilizing isogamy under a bet-hedging strategy, and low fertilization costs stabilizing anisogamy and pheromone production.
Targeting CD301+ macrophage inhibits endometrial fibrosis and improves pregnancy outcome
Authors: Lv Haining , Sun Haixiang , Wang Limin , Yao Simin , Liu Dan , Zhang Xiwen , Pei Zhongrui , Zhou Jianjun , Wang Huiyan , Dai Jianwu , Yan Guijun , Ding Lijun , Wang Zhiyin , Cao Chenrui , Zhao Guangfeng , Hu Yali 
Published: June 2023

AbstractMacrophages are a key and heterogeneous cell population involved in endometrial repair and regeneration during the menstrual cycle, but their role in the development of intrauterine adhesion (IUA) and sequential endometrial fibrosis remains unclear. Here, we reported that CD301+ macrophages were significantly increased and showed their most active interaction with profibrotic cells in the endometria of IUA patients compared with the normal endometria by single-cell RNA sequencing, bulk RNA sequencing and experimental verification. Increasing CD301+ macrophages promoted the differentiation of endometrial stromal cells into myofibroblasts and resulted in extracellular matrix accumulation, which destroyed the physiological architecture of endometrial tissue, drove endometrial fibrosis and ultimately led to female infertility or adverse pregnancy outcomes. Mechanistically, CD301+ macrophages secreted GAS6 to activate the AXL/NF-κB pathway, up-regulating the profibrotic protein synthesis. Targeted deletion of CD301+ macrophages or inhibition of AXL by Bemcentinib blunted the pathology and improved the outcomes of pregnancy in mice, supporting the therapeutic potential of targeting CD301+ macrophages for treating endometrial fibrosis.