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Tandem mass spectrometry (MS/MS) is the gold standard for intact glycopeptide identification, enabling peptide sequence elucidation and site-specific localization of glycan compositions. Beam-type collisional activation is generally sufficient for N- glycopeptides, while electron-driven dissociation is crucial for site localization in O- glycopeptides. Modern glycoproteomic methods often employ multiple dissociation techniques within a single LC-MS/MS analysis, but this approach frequently sacrifices sensitivity when analyzing multiple glycopeptide classes simultaneously. Here we explore the utility of intelligent data acquisition for glycoproteomics through real-time library searching (RTLS) to match oxonium ion patterns for on-the-fly selection of the appropriate dissociation method. By matching dissociation method with glycopeptide class, this autonomous dissociation-type selection (ADS) generates equivalent numbers of N- glycopeptide identifications relative to traditional beam-type collisional activation methods while also yielding comparable numbers of site-localized O- glycopeptide identifications relative to conventional electron transfer dissociation-based methods. The ADS approach represents a step forward in glycoproteomics throughput by enabling site-specific characterization of both N- and O- glycopeptides within the same LC-MS/MS acquisition.

Regulatory frameworks for artificial intelligence (AI) are needed to mitigate risks while ensuring the ethical, secure, and effective implementation of AI technology in healthcare and population health. In this article, we present a synthesis of 141 binding policies applicable to AI in healthcare and population health in the EU and 10 European countries. The EU AI Act sets the overall regulatory framework for AI, while other legislations set social, health, and human rights standards, address the safety of technologies and the implementation of innovation, and ensure the protection and safe use of data. Regulation specifically pertaining to AI is still nascent and scarce, though a combination of data, technology, innovation, and health and human rights policy has already formed a baseline regulatory framework for AI in health. Future work should explore specific regulatory challenges, especially with respect to AI medical devices, data protection, and data enablement., (© 2024. The Author(s).)

Cyclodipeptide synthases (CDPSs) are enzymes that use aminoacylated tRNAs as substrates to produce cyclic dipeptide natural products acting as anticancer and neuroprotective compounds. Many CDPSs, however, suffer from instability and poor recyclability, while enzyme immobilization can enhance catalyst efficiency and reuse. Here, the CDPS enzyme from Parcubacteria bacterium RAAC4_OD1_1 was immobilized using three different supports: biochar from waste materials, calcium-alginate beads, and chitosan beads. Immobilization of active PbCDPS was successful, and production of the cyclodipeptide cyclo (His-Glu) (cHE) was confirmed by HPLC-MS. Biochar from spent coffee activated with glutaraldehyde, alginate beads, and chitosan beads activated with glutaraldehyde led to a 5-fold improvement in cHE production, with the immobilized enzyme remaining active for seven consecutive cycles. Furthermore, we co-immobilized three enzymes participating in the cascade reaction yielding cHE (PbCDPS, histidyl-tRNA synthetase, and glutamyl-tRNA synthetase). The enzymatic cascade successfully produced the cyclic dipeptide, underscoring the potential of immobilizing various enzymes within a single support. Importantly, we demonstrated that tRNAs remained free in solution and were not adsorbed by the beads. We paved the way for the immobilization of enzymes that utilize tRNAs and other complex substrates, thereby expanding the range of reactions that can be exploited by using this technology., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Objective: To determine the common understanding of focal muscle spasticity guidelines amongst clinicians working in spasticity clinics. To examine the facilitators and barriers to their implementation as well as their influence on clinic processes., Design: A qualitative study based on a phenomenological approach., Setting: Online videoconferencing platform., Participants: Sixteen experienced multi-disciplinary clinicians providing specialised care across 12 spasticity clinics in Victoria, Australia., Intervention: Observational., Main Measures: Two independent reviewers performed line by line coding of transcripts. Reflexive thematic analysis was undertaken with themes/subthemes inductively derived., Results: Seven key themes emerged. First, knowledge of specific guideline recommendations was low amongst some clinicians. Second, there is a lack of health service resources to support guideline implementation. Third, a limited evidence base for guidelines affected clinicians' willingness to implement the recommendations. Fourth, peer support was highly valued but opportunities to collaborate were limited. Fifth, a large amount of intrinsic motivation and personal time was required from clinicians to successfully implement guideline recommendations. Sixth, the standardisation of clinic processes was one way in which clinicians felt they could better align their clinical practice to guidelines. Lastly, guidelines overall had a moderate influence on spasticity clinic processes., Conclusions: Knowledge of recommendations varied but, overall, guidelines had an influence on clinic processes and staff perceptions across the state-wide services. Health service resources, limited evidence for guideline recommendations and time constraints were considered barriers to spasticity guideline implementation. Multi-disciplinary expertise and teamwork, the individual's motivation to change and inter-clinic collaboration were considered to be the facilitators., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To map existing literature about concussion management in older people, identifying and analyzing gaps in our understanding., Context: Concussion injuries affect older people, yet little guidance is available about how to approach concussion management with older people. Research does not always include older populations, and it is unclear to what extent standard concussion management is appropriate for older people., Design: Scoping review., Method: A structured literature search was conducted using 4 databases to identify existing literature relating to concussion management in older people. Studies that assessed outcomes relating to the management of concussion/mild traumatic brain injury in those 65 years or older were included and mapped according to the main themes addressed., Results: The search yielded a total of 18 articles. Three themes related to early management (use of anticoagulants n = 6, intracranial lesions n = 3, and service delivery for older people n = 5), and 1 theme related to general management (cognitive issues n = 4). A lack of articles exploring general management in older people was observed., Conclusion: Existing literature indicates that specific management strategies are needed for older people with concussion, especially in early management. This review highlights that good evidence is available about early management and this is reflected in some guidelines, yet little evidence about general management is available and this gap is not acknowledged in guidelines. Distinct approaches to early management in older people are clearly recommended to mitigate the risk of poor outcomes. In contrast, general concussion management for older people is poorly understood, with older people poorly represented in research. A better understanding is needed because-as observed in early management-older people have distinct characteristics that may render standard management approaches unsuitable., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Sepsis is a life-threatening condition that results from a dysregulated host response to infection, leading to organ dysfunction. Despite the prevalence and associated socioeconomic costs, treatment of sepsis remains limited to antibiotics and supportive care, and a majority of intensive care unit (ICU) survivors develop long-term cognitive complications post-discharge. The present study identifies a novel regulatory relationship between amyloid-β (Aβ) and the inflammasome-caspase-1 axis as key innate immune mediators that define sepsis outcomes., Methods: Medical ICU patients and healthy individuals were consented for blood and clinical data collection. Plasma cytokine, caspase-1 and Aβ levels were measured. Data were compared against indices of multiorgan injury and other clinical parameters. Additionally, recombinant proteins were tested in vitro to examine the effect of caspase-1 on a functional hallmark of Aβ, namely aggregation., Results: Plasma caspase-1 levels displayed the best predictive value in discriminating ICU patients with sepsis from non-infected ICU patients (area under the receiver operating characteristic curve=0.7080). Plasma caspase-1 and the Aβ isoform Aβx-40 showed a significant positive correlation and Aβx-40 associated with organ injury. Additionally, Aβ plasma levels continued to rise from time of ICU admission to 7 days post-admission. In silico , Aβ harbours a predicted caspase-1 cleavage site, and in vitro studies demonstrated that caspase-1 cleaved Aβ to inhibit its auto-aggregation, suggesting a novel regulatory relationship., Conclusions: Aβx-40 and caspase-1 are potentially useful early indicators of sepsis and its attendant organ injury. Additionally, Aβx-40 has emerged as a potential culprit in the ensuing development of post-ICU syndrome., Competing Interests: Conflict of interests: All authors have verified there are no conflicts of interest., (Copyright ©The authors 2024.)

Comprehensive health data interoperability is recognized as an essential element of high-functioning and accountable health service. Canada is lagging in health data interoperability compared to international comparators, and lacks a comprehensive approach to human factor interoperability, defined as system-level relationships that impact the capacity of health sector stakeholders to adopt harmonized health data standards and technology. Without addressing these system-level relationships, the adoption of harmonized health data standards and technology will be obstructed and Canadians will be underserved. The proposed health data interoperability framework articulates the factors that Canada needs to address to optimize health data design to support quality health programs and services., (Copyright © 2024 Longwoods Publishing.)