bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measles Virus Genotype A in Canada’s Capital Region Wastewater Associated with Public Health Vaccination Initiatives
Authors: Tomalty Emma , Mercier Élisabeth , Pisharody Lakshmi , Nguyen Tram , Tian Xin , Kabir Md Pervez , Wong Chandler , Addo Felix , Hegazy Nada , Renouf Elizabeth , Wan Shen , Delatolla Robert 
Published: October 2024

AbstractThe recent global resurgence of measles in 2023-2024, despite its preventability through vaccination, is a significant public health concern largely driven by decreased vaccination coverage during the SARS-CoV-2 pandemic. To address this resurgence and to restore vaccine coverage disrupted by the pandemic, Ottawa Public Health intensified vaccination efforts in 2023 and 2024. Additionally, a research initiative began in April 2024 to monitor Ottawa wastewater for measles virus (MeV) using established wastewater and environmental surveillance (WES) protocols. Given the absence of active measles cases in the Ottawa region, unexpected positive MeV detections through RT-qPCR prompted genotypic analysis as well as retrospective analysis of archived RNA samples dating back to 2020. The genotypic analysis identified positive detection to belong to genotype A, the progenitor strain of the viral vaccines, marking the first report of MeV RNA and MeV vaccine shedding in North American wastewater. Positive detections in both real-time and retrospectively analysed samples coincided with the increased vaccination efforts by Ottawa Public Health. These finding emphasize the importance of integrating genotypic analysis into WES practices to mitigate possible confounding factors, such as vaccine shedding into wastewater. Additionally, this research highlights the potential application of MeV WES for monitoring community immunization efforts in real time. Implementing the findings of this study for MeV WES, as well as for other re-emerging viruses, will enhance the accuracy of public health response and optimize resource allocation.
Innovative Strategies for Enhancing Signal-to-Noise Ratio in Single-molecule Imaging: The Influence of Molecular Motion
Authors: Bu Gayun , Kang Gyeongho , Park Seongyu , Jeon Jae-Hyung , Lee Jong-Bong 
Published: October 2024

ABSTRACTSingle-molecule fluorescence imaging has extensively revealed the dynamic and structural characteristics of biomolecules. However, its application is limited by the upper concentration of fluorophore-tagged biomolecules, which is in the sub-ten nanomolar range. We found that the signal-to-noise ratio (SNR) in single-molecule fluorescence imaging is strongly influenced by the size of fluorophore-labeled molecules in solution. Our computational simulations suggest that the faster diffusion of background fluorophores can enhance the SNR of target molecules. Moreover, we identified that the molecular motion through fluid flow can improve SNR. This study provides a novel perspective by emphasizing the importance of molecular motion in SNR and propose a rapid barrier-free method to increase the upper concentration limit in single-molecule imaging.
Chromosome-scale reference genome ofPectocarya recurvata, a species with one of the smallest genome sizes in Boraginaceae
Authors: Northing Poppy C. , Pelosi Jessie A. , Venable D. Lawrence , Dlugosch Katrina M. 
Published: October 2024

ABSTRACTPremisePectocarya recurvata(Boraginaceae), a native species of the Sonoran Desert, has served as an important model system for a suite of ecological and evolutionary studies. Despite its relevance as an eco-evolutionary model, no reference genome assemblies in the Cynoglossoideae subfamily have been published.MethodsUsing PacBio HiFi sequencing, we assembled a reference genome forP. recurvataand annotated coding regions with full-length transcripts from an Iso-Seq transcriptome library. We assessed genome completeness with BUSCO and used flow cytometry and K-mer analysis to estimate the genome size ofP. recurvata.ResultsThe chromosome-scale reference genome assembly forP. recurvatawas 216.0 Mbp long with a contig N50 of 12.1 Mbp. Our assembly included 12 primary contigs bounded by telomeres at all ends but one, consistent with the 12 chromosomes documented for the species. The chromosomes covered 158.3 Mbp and contained 30,655 predicted genes. Our measured haploid genome size from the same population was 386.5 Mbp, among the smallest for Boraginaceae. Genomic analyses suggested that this may reflect a recent autotetraploid, such that predicted diploid genome size would be even smaller and similar to the assembly size.DiscussionTheP. recurvataassembly and annotation provide a high-quality genomic resource in a sparsely represented area of the Angiosperm phylogeny. Our new genome will enable future ecophysiology, biogeography, and phylogenetics research.
Discovery of Natural MCL1 Inhibitors using Pharmacophore modelling, QSAR, Docking, ADMET, Molecular Dynamics, and DFT Analysis
Authors: Das Uddalak , Chanda Tathagata , Kumar Jitendra , Peter Anitha 
Published: October 2024

ABSTRACTMcl-1, a Bcl-2 family protein, is a key regulator of apoptosis and is often overexpressed in cancers such as lung, breast, pancreatic, cervical, ovarian cancers, leukemia, and lymphoma. Its role in inhibiting apoptosis enables tumor cells to evade cell death and contributes to drug resistance. Targeting Mcl-1 is crucial in inducing apoptosis and overcoming resistance to therapies that target other anti-apoptotic proteins, making it a prominent target for anticancer drug development across multiple malignancies. So, our study aimed to discover potent antileukemic compounds targeting MCL1. We began by selecting a diverse set of molecules from the BindingDB database to construct a structure-based pharmacophore model, which was subsequently used to virtually screen a library of 407,270 compounds from the COCONUT database. Subsequently, we developed an e-pharmacophore model using the co- crystallized inhibitor AMG-176, for further screening. A QSAR model was then implemented to estimate the IC50values of these compounds, filtering those with predicted IC50values below the median. The top hits were subjected to molecular docking and MMGBSA binding energy calculations against MCL1, leading to the selection of two promising candidates for further ADMET analysis. To assess their electronic properties, density functional theory (DFT) calculations were conducted, which included geometry optimization, frontier molecular orbital (FMO) analysis, HOMO-LUMO gaps, and global reactivity descriptors. These analyses confirmed favourable profiles and reactivity for the chosen compounds. In addition, predictions for physicochemical and ADMET properties aligned well with the expected bioactivity and safety profiles of the candidates. Molecular dynamics (MD) simulations further validated their strong binding affinity and stability, positioning them as potential MCL1 inhibitors. Our comprehensive computational approach highlights these compounds as promising and safe antileukemic agents, with futurein vivoandin vitrovalidation recommended for further confirmation.
Understanding repair and replacement of prosthetic limbs using routinely-collected data: a retrospective study over three decades in Cambodia
Authors: Dickinson A S , Gates L , Metcalf C D , Owen C , Kheng S , Heang T , Sam B , Harte C , Simpson S , Worsley P R , Ostler C , Donovan-Hall M , Channon A A 
Published: October 2024

AbstractProsthetic limbs deliver major quality of life and socioeconomic benefits for people with amputation, particularly in low-resource settings. The value of administrative data analysis to enable sustainable health care improvement is established, but there has been limited research into the failure, repair, and replacement of prosthetic limbs. Survivorship data is sparse and highly variable, and rarely addresses differences between demographic groups.Therefore, we investigated the distribution of time between device delivery, repair and replacement for a Cambodian cohort, considering the influence of a range of service delivery, user demographic and health characteristics. We conducted Kaplan-Meier survival analysis, and a Cox model to compare repair and replacement likelihood between groups.The study explored 14,822 device deliveries to 6,986 clients, with median 3 devices/person (interdecile range IDR 1–9), and 22,205 repairs, median 1 repair/device (IDR 0–4). The median device survival before repair was 237 days (IDR 38–854), and replacement was 727 days (IDR 208–2154). Devices used by people in more active occupations were repaired earlier, and devices were replaced earlier when used by children, replaced later for upper- than lower-limb devices, and replaced earlier for volume change than for wear and tear. Several less intuitive trends were revealed such as different preferences or capacities between clinics for device repair vs. replacement, and earlier device repair and replacement for women than men.Prosthetic limb repair and replacement is influenced both by the device’s durability and the user’s access to well-resourced physical rehabilitation services. A worn-out device may indicate poor quality, or the opposite: that it fitted well and enabled great mobility. However, such analysis may enable us to identify groups who are less well-served by current devices or rehabilitation models, and contribute to cost effectiveness analysis of current services. Furthermore, the findings represent benchmark data against which engineers could measure new technologies, to ensure that innovation justifies its inherent risk by offering a genuine improvement which balances functionality, cost, and durability.
Domestic abuse, primary care and child mental health services: A systems analysis of service coordination from professionals’ perspectives
Authors: Powell Claire , Adisa Olumide , Herlitz Lauren , Bains Shivi , Eyrúnardóttir Clark Sigrún , Deighton Jessica , Syed Shabeer , Gilbert Ruth , Feder Gene , Howarth Emma 
Published: October 2024

AbstractObjectiveWe explored how services work together to support parents and children experiencing both parental intimate partner violence (IPV) and parental or child mental health problems by drawing on the perspectives of professionals working in primary care, children and young people’s mental health services (CYPMHS), and domestic abuse services.MethodsWe conducted a qualitative study, interviewing 38 professionals in three geographically contrasting local authority areas in England. We carried out framework analysis using a systems approach and mapping techniques to understand the service interrelationships and boundary judgements of professionals.ResultsThe relationships between domestic abuse services, CYPMHS, and primary care were complex, involving funders and commissioners, local authority strategic groups, and wider services such as schools and children’s centres. Participants consistently identified a gap in the relationship between statutory CYPMHS and domestic abuse services. Other service gaps were for children living with ongoing or intermittent IPV and for children and parents with needs falling below or between service thresholds. There was a gap in support services for users of abusive behaviour to prevent future IPV. An overview of staff perspectives revealed differing views on treating the effects of trauma, and the co-ordination and sequencing of care.ConclusionImproving the response to children and adults experiencing mental health problems in the wake of IPV requires a systems perspective to understand the barriers to service co-ordination. Our findings indicate a particular need to address the gap between CYPMHS and domestic abuse services. Current ways of working with adults could be adapted for children, in addition to learning from examples of best practice in the study sites.
Leadership and Governance, Financing, and Coordination and their Impact on the Operationalization of Health Interventions in the Humanitarian-Development Nexus in South Sudan
Authors: Qaddour Amany , Yan Lauren , Wendo Dan , Elisama Laura , Lindahl Christopher , Spiegel Paul 
Published: October 2024

ABSTRACTSouth Sudan ranks among the most fragile nations in the world. Protracted conflict and recurrent shocks have weakened its health system and contributed to high maternal and child mortality rates, despite large amounts of humanitarian and development assistance injected into the country since independence. Factors related to the leadership and governance, financing, and coordination of health services impact the feasibility of implementing the humanitarian-development nexus (HDN). Researchers employed a qualitative case study design drawing from document reviews and individual and group semi-structured interviews with humanitarian and development stakeholders in South Sudan (Juba capital and Bor town). Data was analyzed and findings were synthesized and organized into distinct themes. Forty-one interviews were conducted with 68 participants between November 2022 and January 2023, and 57 documents were analyzed. Findings showed that limited government investment in the health sector has perpetuated reliance on international assistance, and barriers to engagement with government counterparts have restricted coordination. Some nascent HDN coordination platforms exist with minimal political buy-in. Recent reductions in development health funding have complicated progress towards longer-term development objectives, including health systems strengthening. Structural barriers within multi-mandate agencies and differences in programming cycles, funding, and reporting contribute to silos. Continued fragility, a restricted operational environment, shrinking funds, and fragmented coordination have made it challenging to plan, finance, and implement HDN-health interventions. Informal efforts to bridge silos between humanitarian and development actors should become more formalized to use resources more efficiently. Despite certain restrictions in engagement with government, coordination and planning at the sub-national level may still be feasible. Such engagement should be enhanced to ensure sustainability of health services. Investment in health systems strengthening and resilience by humanitarian and development actors should enable communities to absorb recurrent shocks and prevent backsliding in health provision.
Extensive monolayer formation depends on a subpopulation of transplanted human iPSC-derived RPE cells
Authors: Tessmer Karen , Gasparini Sylvia J. , Schmidtke Klara , Adhikari Trishla , Michalke Lea , Hammer Juliane , Loureiro Liliana R. , Last Annika , Chelius Nadine , Kurtz Annett , Johannsen Hannah , Carido Madalena , Ferguson Susanne , Petzold Andreas , Friedrich Ulrike A. , Kurth Thomas , Dahl Andreas , Feldmann Anja , Almedawar Seba , Knöbel Sebastian , Ader Marius 
Published: October 2024

AbstractLoss of retinal pigment epithelium (RPE) cells in the eye leads to photoreceptor death and vision loss. Cell replacement strategies using RPE derivedin vitrofrom pluripotent stem cells (PSCs) has emerged as a promising therapeutic strategy. Generation of polarized monolayers represents an essential prerequisite for proper RPE function, however, monolayer formation following transplantation of RPE cell suspensions has not been systematically assessed. Using the sodium iodate mouse model of RPE depletion, significant increase in monolayer formation capacity of passage (P) 1 vs. P2 human iPSC-derived RPE cells was observed three weeks after transplantation. Transplant-derived monolayers showed characteristic apicobasal polarity, RPE marker expression, phagocytosis function, and preservation of the host outer nuclear layer. The cell surface marker panel CD54+/PSA-NCAM-was identified to enrich for an RPE subpopulation with high potential for monolayer formation following transplantation. Results underline the importance of defining and isolating competent cell subpopulations for successful RPE transplantation.
Genetic diversity, population structure and differentiation of farmed and wild African catfish (Clarias gariepinus) in Nigeria
Authors: Sanda Mark K. , Metcalfe Neil B. , Capstick Maria , Nichols Jenna , Mable Barbara K. 
Published: October 2024

AbstractThe African catfish (Clarias gariepinus) is a commercially important species, for both fisheries and aquaculture, and is now the most commonly farmed fish in sub-Saharan Africa. However, knowledge about the genetic diversity and population structure of wild and farmed populations, which is crucial for effective conservation and sustainable aquaculture management, is scarce. Using mitochondrial DNA (mtDNA) cytochrome c oxidase 1 gene (COI) sequencing and genomic analysis using triple restriction site-associated DNA sequencing (3RAD), we investigated the genetic diversity and population structure of farmed and wildC. gariepinuspopulations from Nigeria, including an albino form found in the wild. Eleven COI haplotypes were identified, of which seven were unique to wild samples. Wild sampling sites had a slightly broader range and higher maximum values for observed heterozygosity (Ho= 0.109 – 0.165), expected heterozygosity (He= 0.111 – 0.216), and nucleotide diversity (pi= 0.125 – 0.225) compared to the farmed populations (Ho= 0.118 – 0.147,He= 0.112-0.144,pi= 0.117 – 0.151). Conversely, genetic differentiation (Fst) was higher among farmed sampling sites compared to the wild ones and there was high genetic differentiation between the farmed and wildC. gariepinussampling sites (Fst= 0.31 – 0.47). Despite evidence for admixture for both farmed and wild fish, there was little evidence of admixture between the two groups. Nevertheless, both mtDNA and 3RAD data strongly suggested that the albino fish, collected from the wild, were in fact farm escapees. Despite overall differentiation farmed genotypes suggesting that overall genetic integrity of wild fish has been maintained, this evidence of escape provides a warning about potential risks of increasing aquaculture activities. Specifically, this indicates the need for greater regulation of fish farms to monitor and reduce the risk of escapes.
Distinct neuronal processes in the ventromedial prefrontal cortex mediate changes in attention load and nicotine pro-cognitive effects
Authors: Vouillac-Mendoza Caroline , Biendon Nathalie , Dovero Sandra , Guillem Karine 
Published: October 2024

AbstractThe prefrontal cortex (PFC) plays a key role in attention. In particular, neuronal activity in the ventromedial PFC (vmPFC) has been implicated in the preparatory attentional period that immediately precedes cue presentation. However, whether vmPFC neuronal activity during this preparatory period is also sensitive to changes in task demand and to the pro-cognitive effects of nicotine remained to be investigated. Here, we usedin vivoelectrophysiology to record vmPFC neuronal activity during two distinct manipulations: a task manipulation that increased task demand by reducing the cue stimulus duration (from 1s to 0.5s), and a pharmacological manipulation by administrating an acute nicotine injection (10 µg/inj, i.v.) before the session. We found that increasing task demand decreased attentional performances and vmPFC precue neuronal activity, but had no effect on gamma oscillations. In contrast, nicotine injection increased attention and gamma oscillations, but almost abolished vmPFC phasic precue responses. Together, these findings indicate the existence of two distinct neuronal mechanisms operating at different timescales and suggests that allocation of attention could be achieved through multiple complementary neuronal mechanisms within the vmPFC.
Stabilizing selection and adaptation shapecisandtransgene expression variation inC. elegans
Authors: Bell Avery Davis , Valencia Francisco , Paaby Annalise B. 
Published: October 2024

AbstractAn outstanding question in the evolution of gene expression is the relative influence of neutral processes versus natural selection, including adaptive change driven by directional selection as well as stabilizing selection, which may include compensatory dynamics. These forces shape patterns of gene expression variation within and between species, including the regulatory mechanisms governing expression incisandtrans. In this study, we interrogate intraspecific gene expression variation among seven wildC. elegansstrains, with varying degrees of genomic divergence from the reference strain N2, leveraging this system’s unique advantages to comprehensively evaluate gene expression evolution. By capturing allele-specific and between-strain changes in expression, we characterize the regulatory architecture and inheritance mode of gene expression variation withinC. elegansand assess their relationship to nucleotide diversity, genome evolutionary history, gene essentiality, and other biological factors. We conclude that stabilizing selection is a dominant influence in maintaining expression phenotypes within the species, and the discovery that genes with higher overall expression tend to exhibit fewer expression differences supports this conclusion, as do widespread instances ofcisdifferences compensated intrans. Moreover, analyses of human expression data replicate our finding that higher expression genes have less variable expression. We also observe evidence for directional selection driving expression divergence, and that expression divergence accelerates with increasing genomic divergence. To provide community access to the data from this first analysis of allele-specific expression inC. elegans, we introduce an interactive web application, where users can submit gene-specific queries to view expression, regulatory pattern, inheritance mode, and other information:https://wildworm.biosci.gatech.edu/ase/.
Targeting long non-coding RNA RP11-502I4.3 delays the trend of angiogenesis in diabetic retinopathy
Authors: Zeng Lan , Wu Yuhao , Zhu Lijuan , He Junhao , Yuan Yuan , Wang Xiaocong , Tang Kai , Tan Wei 
Published: October 2024

AbstractBased on our previous findings, we hypothesized that the long non-coding RNA RP11-502I4.3 may be involved in angiogenesis associated with Diabetic retinopathy (DR). We investigated the role of RP11-502I4.3 in DR by examining its regulation of vascular endothelial growth factor (VEGF). We assessed differences in RP11-502I4.3 expression between the normal control group and streptozotocin-induced diabetic rats or high glucose (HG)-stimulated human retinal microvascular endothelial cells (HRMECs). VEGF expression was measured with and without lentiviral vectors overexpressing RP11-502I4.3. We analyzed the structural and functional alterations related to DR. Our analysis revealed that RP11-502I4.3 expression was lower in the retinas of diabetic rats and in HG-stimulated HRMECs compared with normal glucose conditions. Overexpressing of RP11-502I4.3 resulted in decreased VEGF levels. Diabetic rats exhibited retinopathy characterized by thinning of the retinal layer thickness, structural changes in the inner and outer nuclear layers, a reduced count of retinal ganglion cells, and the presence of acellular capillaries. The proliferative activity, migration count, and tube formation ability of HG-treated HRMECs were significantly higher than those of the normal control group; however, these changes were delayed by RP11-502I4.3 overexpression. RP11-502I4.3 downregulation in DR appears to promote angiogenesis.