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Objectives: This study sought to describe the 2-year evolution of the intensity and frequency of noncardiac chest pain (NCCP), NCCP-related disability and health-related quality of life in a cohort of emergency department (ED) patients. It also aimed to identify and characterize subgroups of patients who share similar NCCP trajectories., Methods: 672 consecutive patients with NCCP were prospectively recruited in two EDs. NCCP, physical and mental health-related quality of life and pain-related impairment were assessed at baseline and 6 months, 1 year and 2 years after the index ED visit., Results: Significant reductions in the intensity and frequency of NCCP and in NCCP-related disability were observed over time, with 58.1% of patients being considered NCCP-free at the 2-year follow-up. Four trajectories of NCCP intensity were identified through latent class growth mixture modelling: Worsening Trajectory (6.8%), Persistence Trajectory (20.5%), Limited Improvement Trajectory (13.1%) and Remission Trajectory (59.5%). Physical quality of life was significantly higher in the latter two trajectories at all assessment points. Patients in the Remission Trajectory reported a better mental quality of life and a greater decrease in NCCP-related disability over time than those in the other trajectories., Conclusions: Over 40% of ED patients with NCCP experienced persistent biopsychosocial morbidity that warrants further clinical attention., Competing Interests: Declaration of competing interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The study objective was to identify correlates of tap water consumption among adolescents. French-speaking adolescents from the province of Québec (Canada) were recruited in person and online from March to July 2023 using diverse recruitment strategies. Water consumption was measured using the validated French version of a questionnaire specifically designed to measure adolescents' beverage intake. Participants answered an online survey on their attitude towards tap and bottled water which also measured individual and environmental factors that can influence tap water consumption. A total of 218 adolescents (14-17 years; 55.5% female) completed the survey. On average, 79.2% of adolescents' water intake came from tap and 33.5% of them consumed exclusively tap water. Thinking that bottled water is more convenient than tap water was a significant correlate of adolescents' tap water consumption (OR = 0.70; 95% CI: 0.51, 0.95; p = 0.0219). Adolescents who believed that bottled water is more convenient than tap water were less likely to consume exclusively tap water. Public health interventions aimed at promoting adolescents' tap water should strive to make tap water intake be perceived as convenient as bottled water, such as encouraging teenagers to always carry along a reusable water bottle, installing drinking fountains in popular public areas, and increasing the visibility of such fountains., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lydi-Anne Vezina-Im reports financial support was provided by the Centre intégré de santé et de services sociaux (CISSS) de Chaudière-Appalaches. Lydi-Anne Vezina-Im reports financial support was provided by the Fondation de l'Hôtel-Dieu de Lévis. Dominique Beaulieu reports financial support was provided by the Collectif de recherche sur la santé en région. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The recent global COVID-19 pandemic has highlighted treatments for coronavirus infection as an unmet medical need. The main protease (M pro ) has been an important target for the development of SARS-CoV-2 direct-acting antivirals. Nirmatrelvir as a covalent M pro inhibitor was the first such approved therapy. Although M pro inhibitors of various chemical classes have been reported, they are generally less active against nirmatrelvir-resistant variants and have limited pan-coronavirus potential, presenting a significant human health risk upon future outbreaks. We here present a novel approach and utilized DNA-encoded chemical library screening to identify the noncovalent M pro inhibitor 5 , which demonstrated a distinct binding mode to nirmatrelvir. A macrocyclization strategy designed to lock the active conformation resulted in lactone 12 with significantly improved antiviral activity. Further optimization led to the potent lactam 26 , which demonstrated exceptional potency against nirmatrelvir-resistant variants as well as against a panel of viral main proteases from other coronaviruses.

Introduction: The COVID-19 pandemic has had a major impact on nursing staff, resulting in alarming turnover rates. As part of the Quebec (Canada) government's response to the pandemic, nurses have been offered exceptional financial incentives. Considering the cost of these measures, the current article presents the research protocol of a study aiming to explore the impact of financial incentives on full-time equivalent, and retention rates among the nursing staff in two healthcare settings in Quebec., Methods and Analysis: A sequential mixed design (QUANT→QUAL) will be used. The quantitative phase will involve a quantitative descriptive analysis and the qualitative phase will consist of a qualitative descriptive study. Administrative data (working hours, employment status and retention rate) will be analysed over a 4.5-year follow-up (from 1 January 2019 to 30 June 2023) to explore the impact of the financial incentives. Focus groups will explore nurses' views on financial incentives. The results will inform the development of future interventions to mitigate attrition problems among nurses and ultimately improve access to and the continuity of public health services., Ethics and Dissemination: The study has been approved by ethics committees of the participating healthcare settings (Comité d'éthique de la recherche sectorial en santé des populations et première ligne du CIUSSS de la Capitale-Nationale; Comité d'éthique de la recherche du CISSS de Chaudière-Appalaches). The results will be disseminated mainly in scientific publications and at academic conferences in addition to presentations tailored to various non-academic audiences., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Improving care transitions for older adults can reduce emergency department (ED) revisits, and the strain placed upon caregivers. We analyzed whether caregivers felt a change in burden following a care transition, and what may be improved to reduce it., Methods: This mixed-methods observational study nested within LEARNING WISDOM included caregivers of older patients who experienced an ED care transition. Burden was collected with the brief Zarit Burden Interview (ZBI-12), and caregivers also commented on the care transition. A qualitative coding scheme of patient care transitions was created to reflect themes important to caregivers. Comments were randomly analyzed until saturation and themes were extracted from the data. We followed both the SRQR and STROBE checklists., Results: Comments from 581 caregivers (mean age (SD) 64.5 (12.3), 68% women) caring for patients (mean age (SD) 77.2 (7.54), 48% women) were analyzed. Caregivers overwhelmingly reported dissatisfaction and unmet service expectations, particularly with home care and domestic help. Communication and follow-up from the ED emerged as an area for improvement. Caregivers who reported an increased level of burden following a patient's care transition had significantly higher ZBI scores than caregivers who self-reported stable burden levels., Conclusion: Caregivers with increasing, stable, and improved levels of subjective burden all reported areas for improvement in the care transition process. Themes centering on the capacity to live at home and inadequate communication were most frequently mentioned and may represent serious challenges to caregivers. Addressing these challenges could improve both caregiver burden and ED care transitions., (© 2024. The Author(s).)

Competing Interests: Conflicts of interest None disclosed.

Colorectal liver metastases (CLM) affect almost half of all colon cancer patients and the response to systemic chemotherapy plays a crucial role in patient survival. While oncologists typically use tumor grading scores, such as tumor regression grade (TRG), to establish an accurate prognosis on patient outcomes, including overall survival (OS) and time-to-recurrence (TTR), these traditional methods have several limitations. They are subjective, time-consuming, and require extensive expertise, which limits their scalability and reliability. Additionally, existing approaches for prognosis prediction using machine learning mostly rely on radiological imaging data, but recently histological images have been shown to be relevant for survival predictions by allowing to fully capture the complex microenvironmental and cellular characteristics of the tumor. To address these limitations, we propose an end-to-end approach for automated prognosis prediction using histology slides stained with Hematoxylin and Eosin (H&E) and Hematoxylin Phloxine Saffron (HPS). We first employ a Generative Adversarial Network (GAN) for slide normalization to reduce staining variations and improve the overall quality of the images that are used as input to our prediction pipeline. We propose a semi-supervised model to perform tissue classification from sparse annotations, producing segmentation and feature maps. Specifically, we use an attention-based approach that weighs the importance of different slide regions in producing the final classification results. Finally, we exploit the extracted features for the metastatic nodules and surrounding tissue to train a prognosis model. In parallel, we train a vision Transformer model in a knowledge distillation framework to replicate and enhance the performance of the prognosis prediction. We evaluate our approach on an in-house clinical dataset of 258 CLM patients, achieving superior performance compared to other comparative models with a c-index of 0.804 (0.014) for OS and 0.735 (0.016) for TTR, as well as on two public datasets. The proposed approach achieves an accuracy of 86.9% to 90.3% in predicting TRG dichotomization. For the 3-class TRG classification task, the proposed approach yields an accuracy of 78.5% to 82.1%, outperforming the comparative methods. Our proposed pipeline can provide automated prognosis for pathologists and oncologists, and can greatly promote precision medicine progress in managing CLM patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: The purpose of this study was to determine and compare the performance of pre-treatment clinical risk score (CRS), radiomics models based on computed (CT), and their combination for predicting time to recurrence (TTR) and disease-specific survival (DSS) in patients with colorectal cancer liver metastases., Methods: We retrospectively analyzed a prospectively maintained registry of 241 patients treated with systemic chemotherapy and surgery for colorectal cancer liver metastases. Radiomics features were extracted from baseline, pre-treatment, contrast-enhanced CT images. Multiple aggregation strategies were investigated for cases with multiple metastases. Radiomics signatures were derived using feature selection methods. Random survival forests (RSF) and neural network survival models (DeepSurv) based on radiomics features, alone or combined with CRS, were developed to predict TTR and DSS. Leveraging survival models predictions, classification models were trained to predict TTR within 18 months and DSS within 3 years. Classification performance was assessed with area under the receiver operating characteristic curve (AUC) on the test set., Results: For TTR prediction, the concordance index (95% confidence interval) was 0.57 (0.57-0.57) for CRS, 0.61 (0.60-0.61) for RSF in combination with CRS, and 0.70 (0.68-0.73) for DeepSurv in combination with CRS. For DSS prediction, the concordance index was 0.59 (0.59-0.59) for CRS, 0.57 (0.56-0.57) for RSF in combination with CRS, and 0.60 (0.58-0.61) for DeepSurv in combination with CRS. For TTR classification, the AUC was 0.33 (0.33-0.33) for CRS, 0.77 (0.75-0.78) for radiomics signature alone, and 0.58 (0.57-0.59) for DeepSurv score alone. For DSS classification, the AUC was 0.61 (0.61-0.61) for CRS, 0.57 (0.56-0.57) for radiomics signature, and 0.75 (0.74-0.76) for DeepSurv score alone., Conclusion: Radiomics-based survival models outperformed CRS for TTR prediction. More accurate, noninvasive, and early prediction of patient outcome may help reduce exposure to ineffective yet toxic chemotherapy or high-risk major hepatectomies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Montagnon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: People who sustain a traumatic brain injury (TBI) may have to live with permanent sequelae such as mental health problems, cognitive impairments, and poor social participation. The strengths-based approach (SBA) of case management has a number of positive impacts such as greater community integration but it has never been implemented for persons with TBI. To support its successful implementation with this population, it is essential to gain understanding of how the key components of the intervention are perceived within the organization applying the approach., Objectives: Documenting the barriers and facilitators in the implementation of the SBA as perceived by potential adopters., Methods: A qualitative pre-implementation study was conducted using semi-structured interviews with community workers and managers of the community organization where the SBA is to be implemented. Data were analyzed using a deductive approach based on the Consolidated Framework for Implementation Research (CFIR)., Results: The major barriers are associated with the intervention (e.g. adaptability of the intervention) and the external context (e.g. the impact of the pandemic). Perceived facilitators are mainly associated with the internal context (e.g. compatibility with current values)., Conclusion: The barriers and facilitators identified will inform the research team's actions to maximize the likelihood of successful implementation.

Malignant Melanoma that resists immunotherapy remains the deadliest form of skin cancer owing to poor clinically lasting responses. Alternative like genotoxic or targeted chemotherapy trigger various cancer cell fates after treatment including cell death and senescence. Senescent cells can be eliminated using senolytic drugs and we hypothesize that the targeted elimination of therapy-induced senescent melanoma cells could complement both conventional and immunotherapies. We utilized a panel of cells representing diverse mutational background relevant to melanoma and found that they developed distinct senescent phenotypes in response to treatment. A genotoxic combination therapy of carboplatin-paclitaxel or irradiation triggered a mixed response of cell death and senescence, irrespective of BRAF mutation profiles. DNA damage-induced senescent melanoma cells exhibited morphological changes, residual DNA damage, and increased senescence-associated secretory phenotype (SASP). In contrast, dual targeted inhibition of Braf and Mek triggered a different mixed cell fate response including senescent-like and persister cells. While persister cells could reproliferate, senescent-like cells were stably arrested, but without detectable DNA damage and senescence-associated secretory phenotype. To assess the sensitivity to senolytics we employed a novel real-time imaging-based death assay and observed that Bcl2/Bcl-XL inhibitors and piperlongumine were effective in promoting death of carboplatin-paclitaxel and irradiation-induced senescent melanoma cells, while the mixed persister cells and senescent-like cells resulting from Braf-Mek inhibition remained unresponsive. Interestingly, a direct synergy between Bcl2/Bcl-XL inhibitors and Braf-Mek inhibitors was observed when used out of the context of senescence. Overall, we highlight diverse hallmarks of melanoma senescent states and provide evidence of context-dependent senotherapeutics that could reduce treatment resistance while also discussing the limitations of this strategy in human melanoma cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Tchelougou, Malaquin, Cardin, Desmul, Turcotte and Rodier.)

The liver is a highly specialized organ involved in regulating systemic metabolism. Understanding metabolic reprogramming of liver disease is key in discovering clinical biomarkers, which relies on robust tissue biobanks. However, sample collection and storage procedures pose a threat to obtaining reliable results, as metabolic alterations may occur during sample handling. This study aimed to elucidate the impact of pre-analytical delay during liver resection surgery on liver tissue metabolomics. Patients were enrolled for liver resection during which normal tissue was collected and snap-frozen at three timepoints: before transection, after transection, and after analysis in Pathology. Metabolomics analyses were performed using 1H Nuclear Magnetic Resonance (NMR) and Liquid Chromatography-Mass Spectrometry (LC-MS). Time at cryopreservation was the principal variable contributing to differences between liver specimen metabolomes, which superseded even interindividual variability. NMR revealed global changes in the abundance of an array of metabolites, namely a decrease in most metabolites and an increase in β-glucose and lactate. LC-MS revealed that succinate, alanine, glutamine, arginine, leucine, glycerol-3-phosphate, lactate, AMP, glutathione, and NADP were enhanced during cryopreservation delay (all p<0.05), whereas aspartate, iso(citrate), ADP, and ATP, decreased (all p<0.05). Cryopreservation delays occurring during liver tissue biobanking significantly alter an array of metabolites. Indeed, such alterations compromise the integrity of metabolomic data from liver specimens, underlining the importance of standardized protocols for tissue biobanking in hepatology., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Goossens et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We identify a senescence restriction point (SeRP) as a critical event for cells to commit to senescence. The SeRP integrates the intensity and duration of oncogenic stress, keeps a memory of previous stresses, and combines oncogenic signals acting on different pathways by modulating chromatin accessibility. Chromatin regions opened upon commitment to senescence are enriched in nucleolar-associated domains, which are gene-poor regions enriched in repeated sequences. Once committed to senescence, cells no longer depend on the initial stress signal and exhibit a characteristic transcriptome regulated by a transcription factor network that includes ETV4, RUNX1, OCT1, and MAFB. Consistent with a tumor suppressor role for this network, the levels of ETV4 and RUNX1 are very high in benign lesions of the pancreas but decrease dramatically in pancreatic ductal adenocarcinomas. The discovery of senescence commitment and its chromatin-linked regulation suggests potential strategies for reinstating tumor suppression in human cancers., Competing Interests: Declaration of interests The authors declare no competing interests., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

The Gottesman-Kitaev-Preskill (GKP) code encodes a logical qubit into a bosonic system with resilience against single-photon loss, the predominant error in most bosonic systems. Here we present experimental results demonstrating quantum error correction of GKP states based on reservoir engineering of a superconducting device. Error correction is made fully autonomous through an unconditional reset of an auxiliary transmon qubit. We show that the lifetime of the logical qubit is increased from quantum error correction, therefore reaching the point at which more errors are corrected than generated.

Objective: To identify facilitators and barriers to older adults' participation in telehealth interventions for primary prevention and health promotion., Methods: Relevant articles were searched using keywords in Embase and MEDLINE. Study characteristics, type of telehealth interventions and technology involved, as well as facilitators and barriers to their use, were extracted from selected articles. The Unified Theory of Acceptance and Use of Technology 2 (UTAUT2) model was used to organise data., Results: A total of 24 articles (pertaining to 20 studies) were included. Nine facilitators and 11 barriers influencing the participation in telehealth interventions for primary prevention and health promotion among older adults were identified. The most recurrent facilitators were related to the individual's performance expectancy and effort expectancy, as well as the presence of a social dimension associated with the intervention (i.e. having a good relationship with the other participants in the program). The two most prevalent barriers were also related to effort expectancy and performance expectancy, followed by barriers related to the inherent characteristics of the technology and older adults' health condition. Experience, age and gender were also found to moderate technology use and acceptance., Conclusions: This rapid review highlights the importance of adopting a holistic perspective when designing telehealth interventions aimed at preventive and health promotion purposes among older adults., (© 2023 The Authors. Australasian Journal on Ageing published by John Wiley & Sons Australia, Ltd on behalf of AJA Inc’.)

Background The strengths-based approach (SBA) was initially developed for people living with mental health issues but may represent a promising support option for community participation of people living with a traumatic brain injury (TBI). A community-based organisation working with people living with TBI is in the process of adapting this approach to implement it in their organisation. No studies explored an SBA implementation with this population. This study explores the implementation of key components of the SBA in a community-based organisation dedicated to people living with TBI. Methods A qualitative descriptive design using semi-structured interviews (n  = 10) with community workers, before and during implementation, was used. Transcripts were analysed inductively and deductively. Deductive coding was informed by the SBA fidelity scale. Results Group supervision and mobilisation of personal strengths are key SBA components that were reported as being integrated within practice. These changes led to improved team communication and cohesiveness in and across services, more structured interventions, and greater engagement of clients. No changes were reported regarding the mobilisation of environmental strengths and the provision of individual supervision. Conclusion The implementation of the SBA had positive impacts on the community-based organisation. This suggests that it is valuable to implement an adaptation of the SBA for people living with TBI.

Objective: The objective of this review is to assess and synthesize the available qualitative evidence on the experiences of social participation of older adults with an early-onset physical disability., Introduction: Understanding the experiences of social participation among older adults with a physical disability acquired earlier in life can guide the development of interventions and policies. It will also help with fostering meaningful community participation and aid in improving the quality of their social participation., Inclusion Criteria: This review will consider primary studies that explore the experiences of social participation of older adults with an early-onset physical disability. The review will focus on qualitative data, including methods such as phenomenology, grounded theory, ethnography, action research, and feminist research. Studies in French or English will be considered for inclusion, and there will be no limitation on publication dates., Methods: A keyword search strategy will be carried out in MEDLINE (Ovid), PsycINFO (Ovid), CINAHL (EBSCOhost), Web of Science, and the Cochrane Library. ProQuest Dissertations and Theses (ProQuest) will be searched for unpublished articles. Two independent reviewers will perform the screening and inclusion process, assess the quality of the evidence, and complete data extraction. The JBI approach to critical appraisal, study selection, data extraction, and data synthesis (meta-aggregation) will be used. The ConQual approach will be used to establish confidence in the synthesized findings., Review Registration: PROSPERO CRD42022371027., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 JBI.)

The objective of this study was to verify if the consumption of different beverages (such as water, 100% pure fruit juice, and sugar-sweetened beverages (SSBs)) is associated with adolescents' sleep quality. French-speaking adolescents were recruited in person and online throughout the province of Québec (Canada) from the end of March to early July 2023. Beverage consumption and sleep quality were measured using French versions of validated questionnaires specifically designed for adolescents. A total of 218 adolescents (14-17 years; 55.5% female) completed the online survey. Among caffeinated SSBs, energy drink (r s = -0.16; p = 0.0197) and sugar-sweetened coffee (r s = -0.33; p < 0.0001) intake was correlated with adolescents' sleep quality. Energy drink consumption (β = -0.0048; p = 0.0005) and being male (β = 0.6033; p < 0.0001) were associated with adolescents' sleep quality. There was an interaction between sugar-sweetened coffee intake and biological sex that was associated with adolescents' sleep quality ( p = 0.0053). Sugar-sweetened coffee consumption was correlated with adolescent girls' abilities to go to bed (r s = -0.21; p = 0.0203) and fall asleep (r s = -0.28; p = 0.0020), while in boys, it was only significantly correlated with their abilities to go to bed (r s = -0.27; p = 0.0069). Public health interventions aimed at adolescent boys should primarily target lowering energy drink consumption, while those aimed at girls should prioritize sugar-sweetened coffee intake to possibly improve their sleep quality.

Objective: Improving care transitions for older adults can reduce emergency department (ED) visits, adverse events, and empower community autonomy. We conducted an inductive qualitative content analysis to identify themes emerging from comments to better understand ED care transitions., Methods: The LEARNING WISDOM prospective longitudinal observational cohort includes older adults (≥ 65 years) who experienced a care transition after an ED visit from both before and during COVID-19. Their comments on this transition were collected via phone interview and transcribed. We conducted an inductive qualitative content analysis with randomly selected comments until saturation. Themes that arose from comments were coded and organized into frequencies and proportions. We followed the Standards for Reporting Qualitative Research (SRQR)., Results: Comments from 690 patients (339 pre-COVID, 351 during COVID) composed of 351 women (50.9%) and 339 men (49.1%) were analyzed. Patients were satisfied with acute emergency care, and the proportion of patients with positive acute care experiences increased with the COVID-19 pandemic. Negative patient comments were most often related to communication between health providers across the care continuum and the professionalism of personnel in the ED. Comments concerning home care became more neutral with the COVID-19 pandemic., Conclusion: Patients were satisfied overall with acute care but reported gaps in professionalism and follow-up communication between providers. Comments may have changed in tone from positive to neutral regarding home care over the COVID-19 pandemic due to service slowdowns. Addressing these concerns may improve the quality of care transitions and provide future pandemic mitigation strategies., (© 2024. The Author(s).)