bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using routinely-collected, linked data to measure and monitor health system performance in Australia: development of an indicator of continuity of primary health care
Authors: Welsh Jennifer , Soga Kay , Robinson Rachel Freeman , Butler Danielle , Eddowes Rachael , Yazidjoglou Amelia , Douglas Angus , Douglas Kirsty , Lazarevic Nina , Law Hsei-Di , Joshy Grace , Trevenar Sue , Tsheten Tsheten , Webster Adrian , Frost Michael , Cropper Bernice , Dykgraaf Sally Hall , Phillips Christine , Banks Emily , Korda Rosemary J 
Published: December 2024

AbstractObjectiveTo examine a potential new Australian health system indicator—continuity of care (CoC) in general practice—derived from whole-of-population linked administrative data.MethodsUsing data from Census 2016 and 2021 and the Medicare Benefits Schedule, available via the Person-Level Integrated Data Asset (PLIDA), we examined an indicator of CoC in general practice, the Usual Provider Index (UPI), over eight overlapping 2-year periods (2016-17 to 2022-23), and the 2-year period following the introduction of universal telehealth in April 2020). We measured population coverage of the UPI, sociodemographic- and health-related variation in high COC (UPI≥0.7), and changes in CoC over time.ResultsPopulation coverage of the UPI was high (>75%); higher for groups with greater healthcare needs, including older people and people with chronic conditions. Coverage decreased with increasing remoteness. In 2022-23, 36% of those with a UPI score had high CoC; proportions with high CoC were greater for older people, those born overseas, not proficient in English, and with health conditions, but lower for people living in more remote areas. Prior to 2020, 32-33% of the population had high CoC, increasing to 39% in the 2-year period directly following the introduction of universal telehealth.ConclusionWhen derived from whole-of population linked administrative data, the UPI is a suitable indicator of CoC for people with varying healthcare needs, and across different settings. Using new national data assets, the UPI could be included in routine health system reporting as one indicator of quality of care.Online Short SummaryWhat is known?Health system performance monitoring aims to facilitate health system planning and improvement. Whole-of-population linked administrative data may be used to extend current health system indicators in Australia.What this paper adds?We examined a potential new indicator—continuity of care within general practice—by assessing coverage and sensitivity to differences between groups and over time. Coverage was high, those with greater healthcare need had higher continuity, and continuity increased after the introduction of telehealth.What are the implications?New national data assets can be used to derive health system indicators, enhancing insight into Australian healthcare.
Selective Targeting of a Defined Subpopulation of Corticospinal Neurons using a Novel Klhl14-Cre Mouse Line Enables Molecular and Anatomical Investigations through Development into Maturity
Authors: Lustig Jake , Lammers Alexander , Kaiser Julia , Patel Payal , Raghu Aidan , Conner James M. , Nguyen Phong , Azim Eiman , Sahni Vibhu 
Published: December 2024

The corticospinal tract (CST) facilitates skilled, precise movements, which necessitates that subcerebral projection neurons (SCPN) establish segmentally specific connectivity with brainstem and spinal circuits. Developmental molecular delineation enables prospective identification of corticospinal neurons (CSN) projecting to thoraco-lumbar spinal segments; however, it remains unclear whether other SCPN subpopulations in developing sensorimotor cortex can be prospectively identified in this manner. Such molecular tools could enable investigations of SCPN circuitry with precision and specificity. During development, Kelch-like 14 (Klhl14) is specifically expressed by a specific SCPN subpopulation, CSNBC-lat, that reside in lateral sensorimotor cortex with axonal projections exclusively to bulbar-cervical targets. In this study, we generated Klhl14-T2A-Cre knock-in mice to investigate SCPN that areKlhl14+during development into maturity. Using conditional anterograde and retrograde labeling, we find that Klhl14-Cre is specifically expressed by CSNBC-latonly at specific developmental time points. We establish conditional viral labeling in Klhl14-T2A-Cre mice as a new approach to reliably investigate CSNBC-lataxon targeting and confirm that this identifies known molecular regulators of CSN axon targeting. Therefore, Klhl14-T2A-Cre mice can be used as a novel tool for identifying molecular regulators of CST axon guidance in a relatively high-throughput mannerin vivo. Finally, we demonstrate that intersectional viral labeling enables precise targeting of only Klhl14-Cre+ CSNBC-latin the adult central nervous system. Together, our results establish that developmental molecular delineation of SCPN subpopulations can be used to selectively and specifically investigate their development, as well as anatomical and functional organization into maturity.Significance StatementThe cortex connects to brainstem and spinal targets through subcerebral projection neurons (SCPN), which exhibit molecular diversity during development based on their neocortical location and axonal targets. We generated a novel Klhl14-Cre mouse line to utilize this developmental delineation and drive Cre expression in a specific SCPN subpopulation. This developmental specificity enabled investigation of 1) areal locations of Klhl14+ SCPN in mature cortex, 2) their axonal collateralization at maturity, and 3) which genes can control their axon targeting. Using intersectional tools, we can also selectively label these neurons in the adult CNS. Therefore, developmental molecular delineation of SCPN not only provides prospective identification but also enables molecular analysis during development, as well as anatomical and functional investigations in adulthood.
Intrinsic multiplication rate variation of Plasmodium falciparum in clinical isolates prior to elimination in Malaysia
Authors: Stewart Lindsay B. , Lantero Escolar Elena , Philpott James , Cox-Singh Janet , Singh Balbir , Conway David J. 
Published: December 2024

AbstractReplication rates and virulence of pathogens are hypothesised to evolve in response to varying intensity of transmission and competition among genotypes. Under exponential growth conditions in culture, clinical isolates of the malaria parasitePlasmodium falciparumhave variable intrinsic multiplication rates, but comparisons of samples from different areas are needed. To analyse parasites from an area of low endemicity, Malaysian clinical isolates cryopreserved prior to malaria elimination were studied. The mean and range ofP. falciparummultiplication rates in Malaysian isolates was no less than that seen among isolates from more highly endemic populations in Africa, which does not support a hypothesis of adaptation to prevailing levels of infection endemicity. Moreover, the distribution of multiplication rates was similar between isolates with single parasite genotypes and those containing multiple genotypes, which does not support a hypothesis of facultative adjustment to competing parasites. Based on clinical isolates, the findings indicate that parasites may not evolve lower multiplication rates under conditions of reduced transmission, and that the virulence potential is likely to be undiminished in pre-elimination settings. This encourages efforts to eliminate endemic infection completely, as has been achieved at the national level in Malaysia.
Spatially resolved rewiring of mitochondria-lipid droplet interactions in hepatic lipid homeostasis
Authors: Kang Sun Woo Sophie , Brown Lauryn A , Miller Colin B , Barrows Katherine M , Golino Jihye L , Cultraro Constance M , Feliciano Daniel , Cornelius-Muwanuzi Mercedes B. , Tran Andy D , Kruhlak Michael , Lobanov Alexei , Cam Maggie , Porat-Shliom Natalie 
Published: December 2024

AbstractHepatic lipid accumulation, or Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), is a significant risk factor for liver cancer. Despite the rising incidence of MASLD, the underlying mechanisms of steatosis and lipotoxicity remain poorly understood. Interestingly, lipid accumulation also occurs during fasting, driven by the mobilization of adipose tissue-derived fatty acids into the liver. However, how hepatocytes adapt to increased lipid flux during nutrient deprivation and what occurs differently in MASLD is not known. To investigate the differences in lipid handling in response to nutrient deficiency and excess, we developed a novel single-cell tissue imaging (scPhenomics) technique coupled with spatial proteomics. Our investigation revealed extensive remodeling of lipid droplet (LD) and mitochondrial topology in response to dietary conditions. Notably, fasted mice exhibited extensive mitochondria-LD interactions, which were rarely observed in Western Diet (WD)-fed mice. Spatial proteomics showed an increase in PLIN5 expression, a known mediator of LD-mitochondria interaction, in response to fasting. To examine the functional role of mitochondria-LD interaction on lipid handling, we overexpressed PLIN5 variants. We found that the phosphorylation state of PLIN5 impacts its capacity to form mitochondria-LD contact sites. PLIN5 S155A promoted extensive organelle interactions, triglyceride (TG) synthesis, and LD expansion in mice fed a control diet. Conversely, PLIN5 S155E expressing cells had fewer LDs and contact sites and contained less TG. Wild-type (WT) PLIN5 overexpression in WD-fed mice reduced steatosis and improved redox state despite continued WD consumption. These findings highlight the importance of organelle interactions in lipid metabolism, revealing a critical mechanism by which hepatocytes maintain homeostasis during metabolic stress. Our study underscores the potential utility of targeting mitochondria-LD interactions for therapeutic intervention.
Chemoreceptor family in plant-associated bacteria responds preferentially to the plant signal molecule glycerol 3-phosphate
Authors: Velando Félix , Xing Jiawei , Genova Roberta , Cerna-Vargas Jean Paul , Santiago Raquel Vázquez- , Matilla Miguel A. , Zhulin Igor B. , Krell Tino 
Published: December 2024

AbstractPlant pathogens and plant-associated bacteria contain about twice as many chemoreceptors as the bacterial average, indicating that chemotaxis is particularly important for bacteria-plant interactions. However, information on the corresponding chemoreceptors is limited. In this study, we identified the chemoreceptor PacP from the phytopathogenPectobacterium atrosepticum, which exclusively recognized C3 phosphorylated compounds at its sCache ligand binding domain, mediating chemoattraction. Using a motif of PacP amino acid residues involved in ligand binding, we identified a chemoreceptor family, termed sCache_PC3, that was specific for C3 phosphorylated compounds. Isothermal titration calorimetry studies revealed that family members preferentially bound glycerol 3-phosphate, a key plant signaling molecule. Additionally, family members recognized glycerol 2-phosphate and glycolysis intermediates glyceraldehyde 3-phosphate, dihydroxyacetone phosphate and 3-phosphoglycerate. This study presents the first evidence of chemoreceptors that bind phosphorylated compounds. We show that the sCache_PC3 family has evolved from an ancestral sCache domain that respond primarily to Krebs cycle intermediates. Members of the sCache_PC3 family were mainly found in bacteria that interact with plants, including many important plant pathogens such asBrenneria, Dickeya, Musicola, Pectobacterium,andHerbaspirillum. Glycerol 3-phosphate is a signal molecule that is excreted by plants in response to stress and infection. Chemotaxis towards this molecule may thus be a means for bacteria to localize stressed plants and move to infection sites. This study lays the groundwork for investigating the functional importance of chemotaxis to phosphorylated C3 compounds in plant-bacteria interactions and virulence.Significance statementThe bacterial lifestyle has shaped the evolution of signal transduction systems, and the number and type of chemoreceptors varies greatly between bacteria occupying various ecological niches. Our understanding of the relationship between lifestyle and chemoreceptor function is limited and the discovery of a chemoreceptor family in plant-associated bacteria that primarily responds to an important plant signal molecule is a significant advancement, allowing for further studies to determine its physiological relevance. The lack of knowledge about signals recognized by bacterial receptors is currently a major challenge in microbiology. This study illustrates the potential of combining experimental ligand screening with computational ligand prediction to identify signals recognized by uncharacterized receptors.
Enhancer lncRNA LOC730338 limits the innate immune response against lymphoma cells, inhibiting ADAR2-dependent alternative transcription
Authors: Cascione Luciano , Guidetti Francesca , Ramnarayanan Sunandini , Rinaldi Andrea , Spriano Filippo , Zadro Alex , Tarantelli Chiara , Munz Nicolas , Arribas Alberto J. , Johnson Rory , Bertoni Francesco , Napoli Sara 
Published: December 2024

AbstractChronic antigenic stimulation is central to marginal zone lymphoma (MZL) development. While the pharmacological inhibition of the B-cell receptor (BCR) signaling is initially effective, secondary resistance frequently develops. We conducted a CRISPR interference (CRISPRi) screen investigating enhancer-associated long non-coding RNAs (elncRNAs) in MZL cells to identify transcripts crucial to shape their dependence on BCR pathway activation. We identified LOC730338, an elncRNA associated with A-to-I RNA editing, which we renamed ADARreg. Silencing ADARreg re-sensitized tumor cells to BCR pathway inhibition by modulating ADAR2 nuclear translocation and altering intronic RNA editing. The process preferentially affected genes that enhance immune responses, such as STING, IRF3, and p65. ADARreg knockdown also increased lymphoma cell sensitivity to NK cell-mediated cytotoxicity. Our results indicate that targeting elncRNAs like ADARreg represents a potential strategy to overcome drug resistance in lymphoma, also opening new therapeutic opportunities for immunotherapy.
Activation of the ChvG-ChvI pathway promotes multiple survival strategies during cell wall stress inAgrobacterium tumefaciens
Authors: Bouchier Jacob M. , Knebel Emily , Amstutz Jennifer , Torrens Gabriel , Santiago-Collazo Gustavo , McCurry Carli , Weisberg Alexandra J. , Cava Felipe , Brown Pamela J.B. 
Published: December 2024

AbstractAgrobacterium tumefaciensshifts from a free-living soil bacterium to a plant-invading state upon encountering the plant root microenvironment. The acid-induced two- component sensor system ChvG-ChvI drives this shift and triggers a complex transcriptional program that promotes host invasion and survival against host immune defenses. Remarkably, ChvG-ChvI is also activated under cell wall stress conditions suggesting that the transcriptional response may have a broader function. Here, we find that blocking cell wall synthesis either genetically or chemically leads to ChvG-ChvI activation. Mutations in key cell wall synthesis or outer membrane proteins, such as PBP1a, FtsW, and AopA1, suppress ChvG-ChvI activation suggesting that providing structural integrity is a primary function of the ChvG-ChvI regulon. Here, we investigated regulon components for this function. First, the exopolysaccharide succinoglycan confers tolerance to multiple β-lactam antibiotics targeting different enzymes by forming a protective barrier around the cells. Next, a Class D β-lactamase is expressed which may contribute to the high level of β-lactam resistance inA. tumefaciens. Finally, outer membrane remodeling compensates for the accumulation of cell wall damage by providing structural integrity. Overall, we expand our understanding of mechanisms driving ChvG-ChvI activation and β-lactam resistance in a bacterial plant pathogen.Significance Statements.Activation of the ChvG-ChvI two component system promotes survival when the bacterial cell walls are damaged by a variety of genetic or chemical approachesThe ChvG-ChvI dependent production of the exopolysaccharide succinoglycan, β-lactamase Cbl activity, and outer membrane proteome remodeling all contribute to survival in the presence of β-lactam antibioticsImproved understanding of bacterial stress responses that promote antibiotic tolerance and resistance has the potential to inform development of novel drug targets
Detection of exotic biosecurity threat ribgrass mosaic virus and novel tobamoviruses through metatranscriptomic sequencing of animal gut content
Authors: Mahar Jackie , Mifsud Jonathon C. O. , Van Brussel Kate , Lachenauer Anna E. , Harvey Erin , Turnbull Olivia M. H. , Bonat Stefanie , Newsome Thomas M. , Olsson Annabelle , Chiu-Werner Antje , Jones Menna E. , Holmes Edward C. , Maina Solomon 
Published: December 2024

AbstractRibgrass mosaic virus (RMV) and related viruses of the genusTobamovirus(Virgaviridae) are cruciferous plant pathogens that represent a threat to global horticultural systems. In Australia, they are considered exotic biosecurity threats, and an incursion of these viruses would require rapid and strict control efforts. However, current surveillance methods for these viruses are limited. We examined whether RMV and related tobamoviruses could be detected by deep sequencing of gut metatranscriptomes of vertebrate animals and ticks. Using this method, we discovered that RMV, as well as a novel relative of RMV, and two highly diverse novel tobamoviruses are present in Australia. RMV was detected in multiple sites in both the Australian Capital Territory (ACT) and Tasmania, two regions separated by approximately 700km of land and 200km of water. The novel relative of RMV was detected in the ACT and New South Wales (NSW), while the highly divergent novel tobamoviruses were each detected in a single state, NSW and Queensland (QLD). In addition, Tobacco mild green mosaic virus, which is already known to be present in Australia, was detected in QLD using this method. This work highlights the potential utility of metatranscriptomic sequencing of wild animal gut for the surveillance of biosecurity threats to native and agricultural plant species.ImportancePlant viruses can have devastating impacts on global horticulture. Tobamoviruses (familyVirgaviridae, genusTobamovirus) are among the most damaging seed-borne viruses in horticultural crops, and Australia is free of many of the tobamoviruses that cause major crop losses in other countries. These viruses are extremely difficult to eradicate. Consequently, early detection of incursions is key to the control of these viruses in Australia, alongside rapid deployment of eradication and management plans. Current biosecurity surveillance methods in Australia rely on visual inspection, immunological assays, and molecular methods such as screening of imported seed lots. This study introduces a complementary approach that utilises unbiased metatranscriptomic sequencing of animal gut material to detect cryptic plant viruses circulating in nature. Using this approach, we detected five different tobamovirus circulating in Australia, including a virus thought to be exotic and three novel viruses. This unique approach highlights alternative options for surveillance/detection of exotic crop viruses.
Description, Development and Application of the Integrated Transport and Health Impact Modelling Tool for Global Cities (ITHIM-Global)
Authors: Khreis Haneen , Abbas Ali , Gil-Sanchez Daniel , Tatah Lambed , Schroeder Anna , Goel Rahul , Brand Christian , Johnson Rob , Woodcock James 
Published: December 2024

AbstractThe Integrated Transport and Health Impact Modelling Tool for Global Cities (ITHIM-Global) was developed as an open-source tool to assess the impacts of transport mode shifts on public health and the environment in low- and middle-income countries (LMICs) where the need for such assessment is urgent and rising. The model simulates the impacts on all-cause and cause-specific mortality and years of life lost outcomes through a multi-pathway framework, specifically including physical activity, air pollution exposure, and road traffic fatalities. In addition, the model estimates changes in carbon dioxide emissions resulting from these mode shifts. ITHIM-Global employs a quasi-microsimulation approach that enables individualized exposure estimates by age, sex, and activity levels and utilises up- to-date exposure and dose-response functions that account for the non-linear relationship between physical activity levels and health. To demonstrate its functionality, document its strengths and weaknesses, and aid users, the model was applied to Bogota, Colombia, using three hypothetical scenarios, each shifting 5% of trips to one of bus, car, or cycling. Results indicate that increasing public or active transport modes enhances public health, primarily driven by gains in physical activity and to a lesser extent by reductions in traffic-related emissions. Conversely, a shift to car usage worsens health outcomes due to decreased physical activity and increased pollution exposure. ITHIM-Global serves as a flexible, detailed Health Impact Assessment (HIA) tool adaptable to urban areas across LMICs and this article delves into underlying assumptions and their influence to advance generalisable lessons on risk assessment and model development. The modular structure of ITHIM-Global, its covering of individual and population-level analyses, and extensive documentation provide an accessible, evidence-based approach for city planners and practitioners to optimize transport policies that support public health and mitigate environmental harm.Graphical AbstractHighlightsWe describe the Integrated Transport and Health Impact Modelling Tool for Global cities (ITHIM- Global), designed for low- and middle-income country (LMIC) cities.We apply ITHIM-Global to Bogotá, simulating impacts from three mode shift scenarios with a 5- percentage point increase in car, cycling, and bus shares.We simulate the impacts on physical activity, air pollution, road traffic fatalities, and attributable mortalities and years of life lost.We describe in detail the model’s elements to aid future uptake, development, and extension to other cities. We discuss strengths, weaknesses, and underlying assumptions to advance generalisable lessons on risk assessment and model development.
Significant rise ofChlamydia pneumoniaediagnoses at Marseille University Hospitals, 2024, France
Authors: Edouard Sophie , Attamna Rayane , Million Matthieu , Boschi Céline , Delerce Jeremy , Caputo Aurélia , Stoupan Didier , Diene Seydina , Kacel Idir , Andrieu Claudia , Levasseur Anthony , Chaudet Hervé , Rolain Jean-Marc , Lesage Lucile , Morand Aurélie , Fournier Pierre-Edouard , Lagier Jean-Christophe , Fenollar Florence , La Scola Bernard , Colson Philippe 
Published: December 2024

SUMMARYWe report a 19-fold increase in 2024 of qPCR diagnoses ofChlamydia pneumoniaeinfections in Marseille, Southern France, with 37 cases versus 10 between 2018-2023. These mostly affected children, and young adults. We obtained fourC. pneumoniaegenomes, all of serotype ST16, suggesting an epidemic circulation in our geographical area.