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    Low Remnant Cholesterol and In-Hospital Bleeding Risk After Ischemic Stroke or Transient Ischemic Attack

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    BACKGROUND: Bleeding risk brought by intensive lipid-lowering therapy and low low-density lipoprotein cholesterol is concern-ing, while evidence regarding the relationship between remnant cholesterol and bleeding is frightening. This study aimed to investigate the association between remnant cholesterol at admission and an in-hospital bleeding event after acute ischemic stroke or transient ischemic attack (TIA). METHODS AND RESULTS: A total of 3222 eligible patients admitted to Shanghai Huashan Hospital between 2015 and 2021 with complete lipid data were analyzed. Patients were classified into low (<20.0 mg/dL), moderate (20.0–29.9 mg/dL), and high (≥30 mg/dL) groups by remnant cholesterol. The mean age of patients was 63.0± 13.1 years, including 2301 (71.4%) men and 651 (20.2%) with TIA. The median (interquartile range) of remnant cholesterol was 18.6 (13.5–25.9) mg/dL. After adjustment for confounding variables, patients with low remnant cholesterol had a higher risk of bleeding events (odds ratio, 2.56 [95% CI, 1.12–6.67]) than those with moderate remnant cholesterol. The high remnant cholesterol group was not significantly associated with bleeding risk. Combined assessment of low-density lipoprotein cholesterol and remnant cholesterol further identi-fied patients with the highest risk of bleeding events. CONCLUSIONS: Low remnant cholesterol levels were associated with bleeding events during the acute stage of ischemic stroke and TIA. The assessment of remnant cholesterol could inform the bleeding risk during hospitalization both for patients and physicians in clinical practice

    Judgement and Decision Making in Clinical and Return-to-Sports Decision Making: A Narrative Review

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    Making return-to-sport decisions can be complex and multi-faceted, as it requires an evaluation of an individual’s physical, psychological, and social well-being. Specifically, the timing of progression, regression, or return to sport can be difficult to determine due to the multitude of information that needs to be considered by clinicians. With the advent of new sports technology, the increasing volume of data poses a challenge to clinicians in effectively processing and utilising it to enhance the quality of their decisions. To gain a deeper understanding of the mechanisms underlying human decision making and associated biases, this narrative review provides a brief overview of different decision-making models that are relevant to sports rehabilitation settings. Accordingly, decisions can be made intuitively, analytically, and/or with heuristics. This narrative review demonstrates how the decision-making models can be applied in the context of return-to-sport decisions and shed light on strategies that may help clinicians improve decision quality

    Same-visit hepatitis C testing and treatment to accelerate cure among people who inject drugs (the QuickStart Study): a cluster randomised cross-over trial protocol

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    Introduction: Despite universal access to government-funded direct-acting antivirals (DAAs) in 2016, the rate of hepatitis C treatment uptake in Australia has declined substantially. Most hepatitis C is related to injecting drug use; reducing the hepatitis C burden among people who inject drugs (PWID) is, therefore, paramount to reach hepatitis C elimination targets. Increasing DAA uptake by PWID is important for interrupting transmission and reducing incidence, as well as reducing morbidity and mortality and improving quality of life of PWID and meeting Australia's hepatitis C elimination targets. Methods and analysis: A cluster randomised cross-over trial will be conducted with three intervention arms and a control arm. Arm A will receive rapid hepatitis C virus (HCV) antibody testing; arm B will receive rapid HCV antibody and rapid RNA testing; arm C will receive rapid HCV antibody testing and same-day treatment initiation for HCV antibody-positive participants; the control arm will receive standard of care. The primary outcomes will be (a) the proportion of participants with HCV commencing treatment and (b) the proportion of participants with HCV achieving cure. Analyses will be conducted on an intention-to-treat basis with mixed-effects logistic regression models. Ethics and dissemination: The study has been approved by the Alfred Ethics Committee (number HREC/64731/Alfred-2020-217547). Each participant will provide written informed consent. Reportable adverse events will be reported to the reviewing ethics committee. The findings will be presented at scientific conferences and published in peer-reviewed journals.</p

    Acute neuroinflammation promotes a metabolic shift that alters extracellular vesicle cargo in the mouse brain cortex

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    Neuroinflammation is initiated through microglial activation and cytokine release which can be induced through lipopolysaccharide treatment (LPS) leading to a transcriptional cascade culminating in the differential expression of target proteins. These differentially expressed proteins can then be packaged into extracellular vesicles (EVs), a form of cellular communication, further propagating the neuroinflammatory response over long distances. Despite this, the EV proteome in the brain, following LPS treatment, has not been investigated. Brain tissue and brain derived EVs (BDEVs) isolated from the cortex of LPS-treated mice underwent thorough characterisation to meet the minimal information for studies of extracellular vesicles guidelines before undergoing mass spectrometry analysis to identify the differentially expressed proteins. Fourteen differentially expressed proteins were identified in the LPS brain tissue samples compared to the controls and 57 were identified in the BDEVs isolated from the LPS treated mice compared to the controls. This included proteins associated with the initiation of the inflammatory response, epigenetic regulation, and metabolism. These results allude to a potential link between small EV cargo and early inflammatory signalling

    Consumer involvement in the development and dissemination of chronic kidney disease guidelines: a summary of a meaningful and sustainable approach developed by Caring for Australians and New ZealandeRs with kidney Impairment guidelines

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    Objectives: The involvement of consumers (people with lived experience of disease) in guidelines is widely advocated to improve their relevance and uptake. However, the approaches to consumer involvement in guidelines vary and are not well documented. We describe the consumer involvement framework of Caring for Australians and New ZealandeRs with kidney Impairment Guidelines. Study Design and Setting: We used a descriptive document analysis to collate all relevant policies, documents, e-mails, and presentations on consumer involvement in our organizations. We performed a narrative synthesis of collated data to summarize our evolving consumer involvement approach in guidelines. Results: We involve consumers at all levels of Caring for Australians and New ZealandeRs with kidney Impairment guideline development and dissemination according to their capacity, from conducting consumer workshops to inform the scope of guidelines, to including consumers as members of the guideline Working Groups and overseeing operations and governance as members of the Steering Committee and staff. Our approach has resulted in tangible outcomes including high-priority topics on patient education, psychosocial care, and clinical care pathways, and focusing the literature reviews to assess patient-important outcomes. The ongoing partnership with consumers led to the generation of consumer version guidelines to improve guideline dissemination and translation to support shared decision-making. Conclusion: Meaningful consumer involvement can be achieved through a comprehensive approach across the entire lifecycle of guidelines. However, it must be individualized by ensuring that the involvement of consumers is timely and flexible. Future work is needed to assess the impact of consumer involvement in guideline development

    <b>Applied Artificial Intelligence in High Throughput Plant </b><b>Phenotyping for Recognition of Arabidopsis Ecotypes</b>

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    https://ipmb-2023.p.asnevents.com.au/days/2024-06-25/abstract/103921   Image-based high-throughput plant phenotyping utilises innovative imaging infrastructures to conduct automated and non-invasive time-series measurements of morphological, physiological, biochemical, and ecological traits of plant species. The primary aim is to determine the structure, performance, and tolerance to limitations of an individual plant or group of plants in a laboratory, glasshouse, or field environment. Recognition of plant ecotypes plays an important role while evaluating, selecting, and producing cultivars. However, it is challenging, time-consuming and nearly impossible to correctly identify multiple ecotypes purely based on visual inspection or through manual measurements of phenotypic traits such as plant area. This research aims to classify various ecotypes of the experimental plant known as Arabidopsis thaliana grown under controlled conditions in indoor high-throughput phenotyping environments. 40 ecotypes are scanned from the top-view on a daily basis taking four images using high-resolution RGB and thermal camera. Upon data collection, all images are organised and stored in the database for subsequent use. After that, several deep learning models are optimised, trained, and evaluated to conduct the classification of various ecotypes considering a single or sequence of images at the input of the model. For the sequence of images, models are trained and evaluated in order to desirable performance for specific days after sowing. Owing to the high variability among replicates within ecotypes, certain samples have to be excluded by extracting general leaf phenotypic traits and considering morphological similarity. Finally, applied deep learning models demonstrated a high level of accuracy and precision during the ecotype recognition task, which provides an opportunity to utilise trained models in different indoor environments, for instance, a glasshouse.</p

    The Reddit cannabis subjective highness rating scale: Applying computational social science to explore psychological and environmental correlates of naturalistic cannabis use

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    Social media data provide unprecedented access to discussions of active, naturalistic, and often real-time cannabis use in an era of cannabis policy liberalization. The aim of this study was to explore psychological and environmental correlates of cannabis effects by applying computational social science approaches to a large dataset of unprompted reports of naturalistic cannabis use with corresponding self-reported numerical ratings of subjective highness. Post title text was extracted via the Pushshift dataset from N = 328,865 posts to the r/trees Reddit community, where posters self-assess and disclose how high they feel on a scale from 1 to 10 (M = 6.9, SD = 1.8). Structural topic modelling and Linguistic Inquiry and Word Count (LIWC) dictionary-based approaches were applied to identify (1) frequently discussed topics and (2) text indicative of 5 psychological processes (affective, social, cognitive, perceptual, biological), respectively, as well as to examine relationships between subjective highness and (1) topic prevalence and (2) psychological process word counts. A 40-topic model was selected for interpretation based on semantic coherence and exclusivity. The most discussed topics in a 40-topic model were characterized by references to smoking places, social contexts, positive affect, cognitive states, as well as food and media consumed. In LIWC dictionary analyses, words mentioning affective, social, and cognitive processes were referenced more often than perceptual or body processes. Posters reported greater subjective highness when using language that referred to in-person social environments and lower subjective highness when using language that referred to online social environments and positive affect psychological states. This examination of unprompted online reports of naturalistic cannabis use identified textual content referring to affect and to other people as being associated with perceived effects of cannabis. These affective and social aspects of the cannabis use experience were salient to active posters in this online community and should be integrated into experience sampling methods and behavioral pharmacology research, as well as public health messaging

    Thermal scanners versus spotlighting: New opportunities for monitoring threatened small endotherms

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    Threatened species monitoring is challenging for small, cryptic endotherms that are most effectively detected at night. Low detectability is a challenge for monitoring programmes, resulting in low statistical power and sparse or zero-inflated datasets. To advance conservation management programmes, efforts to address this are required. In recent years thermal scanners have emerged as an effective tool for detecting small endotherms, but the diversity of available thermal tools, focal habitats and target species mean that their applicability in many key scenarios remain untested. We directly compared vehicle-mounted thermal surveys with vehicle-based spotlighting targeting small endotherms in Australian native grasslands. Our targets included both common species that occur at high densities, and species that are notoriously difficult to detect with spotlights, which may occur at very low densities. We completed paired surveys of roosting grassland birds, and nocturnally active small mammals at 22 sites, once using thermal scanners and once using spotlights. Ultimately, distance sampling was conducted across 136 km of transects. Thermal scanners facilitated greater detection distances and higher total detections for small endotherms when compared with spotlighting. Species of greatest conservation concern, the Plains-wanderer (Pedionomus torquatus—Pedionomidae) and Fat-tailed Dunnart (Sminthopsis crassicaudata—Dasyuridae) were only detected using thermal scanners. Detection distances generated for thermal scanners were reduced by higher vegetation density; however, thermal scanners continued to outperform spotlights under this scenario. Observers also detected more stationary animals and fewer birds were flushed upon detection using thermal scanners when compared with spotlighting. Thermal scanners have the potential to improve the quality of monitoring datasets by increasing detection probabilities for small endotherms. We recommend the adoption of thermal scanners as a best-practice tool for monitoring small endotherms in open grassland habitats at night, offering new opportunities to monitor endotherms where monitoring has historically been challenging, inadequate or impossible

    Incomplete transcriptional dosage compensation of chicken and platypus sex chromosomes is balanced by post-transcriptional compensation

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    Heteromorphic sex chromosomes (XY or ZW) present problems of gene dosage imbalance between sexes and with autosomes. A need for dosage compensation has long been thought to be critical in vertebrates. However, this was questioned by findings of unequal mRNA abundance measurements in monotreme mammals and birds. Here, we demonstrate unbalanced mRNA levels of X genes in platypus males and females and a correlation with differential loading of histone modifications. We also observed unbalanced transcripts of Z genes in chicken. Surprisingly, however, we found that protein abundance ratios were 1:1 between the sexes in both species, indicating a post-transcriptional layer of dosage compensation. We conclude that sex chromosome output is maintained in chicken and platypus (and perhaps many other non therian vertebrates) via a combination of transcriptional and post-transcriptional control, consistent with a critical importance of sex chromosome dosage compensation

    Streamlining Protein Fractional Synthesis Rates Using SP3 Beads and Stable Isotope Mass Spectrometry: A Case Study on the Plant Ribosome

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    Ribosomes are an archetypal ribonucleoprotein assembly. Due to ribosomal evolution and function, r-proteins share specific physicochemical similarities, making the riboproteome particularly suited for tailored proteome profiling methods. Moreover, the structural proteome of ribonucleoprotein assemblies reflects context-dependent functional features. Thus, characterizing the state of riboproteomes provides insights to uncover the context-dependent functionality of r-protein rearrangements, as they relate to what has been termed the ribosomal code, a concept that parallels that of the histone code, in which chromatin rearrangements influence gene expression. Compared to high-resolution ribosomal structures, omics methods lag when it comes to offering customized solutions to close the knowledge gap between structure and function that currently exists in riboproteomes. Purifying the riboproteome and subsequent shot-gun proteomics typically involves protein denaturation and digestion with proteases. The results are relative abundances of r-proteins at the ribosome population level. We have previously shown that, to gain insight into the stoichiometry of individual proteins, it is necessary to measure by proteomics bound r-proteins and normalize their intensities by the sum of r-protein abundances per ribosomal complex, i.e., 40S or 60S subunits. These calculations ensure that individual r-protein stoichiometries represent the fraction of each family/paralog relative to the complex, effectively revealing which r-proteins become substoichiometric in specific physiological scenarios. Here, we present an optimized method to profile the riboproteome of any organism as well as the synthesis rates of r-proteins determined by stable isotope-assisted mass spectrometry. Our method purifies the r-proteins in a reversibly denatured state, which offers the possibility for combined top-down and bottom-up proteomics. Our method offers a milder native denaturation of the r-proteome via a chaotropic GuHCl solution as compared with previous studies that use irreversible denaturation under highly acidic conditions to dissociate rRNA and r-proteins. As such, our method is better suited to conserve post-translational modifications (PTMs). Subsequently, our method carefully considers the amino acid composition of r-proteins to select an appropriate protease for digestion. We avoid nonspecific protease cleavage by increasing the pH of our standardized r-proteome dilutions that enter the digestion pipeline and by using a digestion buffer that ensures an optimal pH for a reliable protease digestion process. Finally, we provide the R package ProtSynthesis to study the fractional synthesis rates of r-proteins. The package uses physiological parameters as input to determine peptide or protein fractional synthesis rates. Once the physiological parameters are measured, our equations allow a fair comparison between treatments that alter the biological equilibrium state of the system under study. Our equations correct peptide enrichment using enrichments in soluble amino acids, growth rates, and total protein accumulation. As a means of validation, our pipeline fails to find “false” enrichments in non-labeled samples while also filtering out proteins with multiple unique peptides that have different enrichment values, which are rare in our datasets. These two aspects reflect the accuracy of our tool. Our method offers the possibility of elucidating individual r-protein family/paralog abundances, PTM status, fractional synthesis rates, and dynamic assembly into ribosomal complexes if top-down and bottom-up proteomic approaches are used concomitantly, taking one step further into mapping the native and dynamic status of the r-proteome onto high-resolution ribosome structures. In addition, our method can be used to study the proteomes of all macromolecular assemblies that can be purified, although purification is the limiting step, and the efficacy and accuracy of the proteases may be limited depending on the digestion requirements.</p

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