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The European Resuscitation Council Guidelines 2025, officially launched as the Guidelines on Cardiopulmonary Resuscitation 2025 on 22 October 2025 in Rotterdam and published in Resuscitation (1) as a thematic collection of guideline papers, represent far more than a scheduled update of resuscitation algorithms. That reading would be too narrow. The ERC Guidelines 2025 are better understood as a portrait of a discipline that has entered a new phase in its understanding of the continuum of resuscitation care. In these guidelines, resuscitation medicine is not reduced to the dramatic moment of cardiac arrest. It is presented as a continuum of knowledge, decision-making, technical skill, system organization, ethical responsibility, and longterm outcome. The algorithm retains its grammar, but not the whole language of care. This is what makes the 2025 guidelines important. They document the transformation of resuscitation from an acute technical intervention into a mature clinical discipline situated at the intersection of time, pathophysiology, teamwork, system design, and value-based decision-making. Resuscitation remains inseparable from urgency, but contemporary resuscitation medicine shows that speed without structure, technical correctness without a functioning system, and intensity of treatment without an ethical frame are not enough. Saving life in a critical moment requires not only hands capable of performing the correct intervention, but also an environment in which that intervention can be delivered early, reliably, in the appropriate clinical context, and with a clear pathway to subsequent care.This shift from algorithm to system is visible throughout the guidelines. Resuscitation is no longer merely a question of what happens in the minutes after collapse. It is shaped by how the system works before cardiac arrest, during cardiac arrest, and after return of spontaneous circulation. Recognition of deterioration, activation of help, first aid, basic life support, automated external defibrillation, dispatcher assistance, emergency medical service organization, in-hospital rapid response systems, advanced life support, post-resuscitation care, registries, and audit all form a single clinical and organizational continuum. The chain of survival is therefore not only an educational metaphor. It is an operational responsibility. Survival after cardiac arrest is not the property of an isolated intervention; it is a property of the system.The concept of systems saving lives is consequently one of the central messages of the ERC Guidelines 2025. There is no isolated hero in resuscitation detached from the system. Citizens, dispatchers, first responders, ambulance crews, emergency departments, catheterization laboratories, intensive care units, rehabilitation professionals, and registries are all part of the same trajectory of care. Each enters at a different point, with different competencies, but in relation to the same outcome. Where one link is absent or weak, even an otherwise excellent intervention loses part of its effect. In resuscitation, a system weakness rapidly becomes a biological loss.The technical core of resuscitation has not lost its importance. Quite the opposite. High-quality chest compressions, early defibrillation, adequate ventilation, treatment of reversible causes, and well-conducted advanced life support remain decisive interventions. Their strength lies in simplicity, reproducibility, and clarity. This is precisely why algorithms are indispensable: under cognitive overload, time pressure, and complex team dynamics, they reduce chaos, create a common language, and give rhythm to decision-making. Yet the ERC Guidelines 2025 also remind us that a correct algorithm does not absolve clinicians from thinking. Special circumstances of cardiac arrest demonstrate that standardization and individualization are not opposites. Cardiac arrest is not a diagnosis, but the final common pathway of many pathophysiological processes. Successful resuscitation must therefore be more than a response to the rhythm on the monitor; it must be a response to the cause, the context, and the possibility of meaningful causal intervention.The integration of ethics into the core of resuscitation medicine is another sign of maturity. Decisions to start, continue, or terminate resuscitation are not merely technical judgments about the probability of return of spontaneous circulation. They are clinical decisions framed by patient values, goals of care, proportionality, and previously expressed preferences. Advance care planning, DNACPR decisions, family presence, termination of futile resuscitation, and organ donation are not peripheral subjects that appear after medicine has done its work. They are part of medicine itself. A discipline capable of rapid and aggressive action must be equally capable of determining when such action is meaningful, proportionate, and aligned with what good care would mean for this particular patient.The significance of the ERC Guidelines 2025 also depends on epidemiology, registries, and outcome measurement. Resuscitation medicine must know itself. It must know how many cardiac arrests occur out of hospital and in hospital, who initiates resuscitation, how often an AED is used, how rapidly the system responds, how many patients survive, and in what neurological condition. Without data, quality becomes impression. Registries, audit, and standardized reporting are not administrative ornaments attached to clinical work; they are prerequisites for responsible improvement. Only a measured system can identify its weaknesses, compare itself with others, and move from conviction to quality.Between scientific recommendation and patient survival lies another decisive space: education and implementation. Guidelines do not become a clinical reality because they are published. They become clinical reality when they are translated into teaching, simulation, team training, feedback, debriefing, local protocols, and the everyday culture of practice. In resuscitation, knowledge without rehearsal quickly becomes uncertainty, and rehearsal without measurement becomes ritual. Simulation is not merely an imitation of reality for educational purposes; it is a safe space in which clinical reality can be processed before it occurs in a real patient. Team culture does not arise at the moment of cardiac arrest. It must be built before it.The breadth of the ERC Guidelines 2025 further reminds us that resuscitation medicine is not one physiological world. Newborns at the threshold between intrauterine and extrauterine life, children threatened by hypoxia or shock, adults with cardiac arrest in the community, frail in-hospital patients with previously expressed treatment limitations, and survivors after return of spontaneous circulation all require different forms of reasoning. A unifying principle exists, but its clinical expression changes with age, cause, setting, prognosis, and available resources.One of the key shifts reinforced by the ERC Guidelines 2025 is that return of spontaneous circulation is not the end of resuscitation. It is a threshold event after which another, often more complex, phase of care begins. Diagnosis of the cause of arrest, oxygenation, ventilation, haemodynamic stability, coronary reperfusion, seizure control, temperature management, neurological prognostication, rehabilitation, psychological consequences, and quality of life determine whether biological survival becomes a return to life. Survival to intensive care admission, survival to hospital discharge, and long-term neurological outcome are not interchangeable endpoints. Post-resuscitation care is therefore not an epilogue. It is an integral part of resuscitation, where the true value of acute success is determined.The ERC Guidelines 2025 are therefore not simply a document on how to resuscitate. They are a document on how resuscitation care should be conceived, organized, taught, measured, and ethically grounded. Their greatest challenge begins not at publication, but at implementation. Their significance will be defined by what hospitals, emergency medical services, educators, professional societies, registries, and clinical teams are able to make of them. The value of guidelines is ultimately measured not by their publication but by the people, teams, and systems that transform them into timely, competent, ethical, and measurable care.

We investigate the thermodynamic, structural, and dynamic behavior of a three-dimensional coarse-grained ramp-shoulder fluid derived from effective interactions between polymer-grafted nanoparticles. The interaction combines a softened repulsive ramp with a shallow attractive shoulder, stabilizing competing local organizations over a broad pressure interval. Molecular dynamics simulations reveal density, diffusion, and structural anomalies together with crystalline, amorphous, and fluid regions in the phase diagram. Unlike conventional isotropic core-softened fluids, the anomalous hierarchy becomes partially decoupled: the density anomaly extends beyond the structural anomaly, while the diffusion anomaly becomes closely connected to amorphization and shell migration processes. Analysis of radial distribution functions, excess entropy, translational and orientational order, and coordination-shell organization shows that the anomalies are not controlled solely by shell competition. Instead, they emerge from cooperative radial restructuring in a regime where radial correlations increase without the development of crystalline orientational order. The results indicate that the detailed shape of the softened interaction region strongly influences the structural pathways explored under compression, leading to a regime of amorphous radial frustration associated with anomalous diffusion and frustrated shell reorganization.

Meningioma en plaque (MEP) may rarely mimic subacute or chronic subdural hematoma (SDH) on noncontrast imaging. As middle meningeal artery (MMA) embolization becomes increasingly adopted for the management of SDH, misdiagnosis of an underlying dural tumor may delay definitive treatment and expose patients to interventions that could complicate subsequent resection. The authors present 2 cases of patients with MEP initially diagnosed as subacute SDH and treated with embolization. In both cases, embolization was performed prior to contrast-enhanced imaging, delaying recognition of the underlying tumor. Subsequent clinical and radiographic progression led to definitive diagnosis and surgical intervention. Intraoperatively, both lesions demonstrated marked cortical adherence and extensive invasion, resulting in challenging resections and postoperative neurological morbidity. These findings raise the possibility that embolization of an unrecognized MEP may alter tumor vascular dynamics and increase operative complexity. As MMA embolization becomes more widely used for presumed SDH, occult dural tumors such as MEP may increasingly be encountered as diagnostic pitfalls. In patients with atypical clinical presentation or unusual radiographic features, contrast-enhanced imaging should be obtained before or immediately after embolization to exclude an underlying neoplasm. Early recognition may prevent delays in care and avoid embolization-related vascular changes that could complicate definitive surgical treatment. https://thejns.org/doi/10.3171/CASE26492.

An algorithm for the black-box generation of high-quality system-specific machine-learning interatomic potentials (MLIPs) for gas-phase reactions in the electronic ground state is presented. It relies on the self-consistent fine-tuning of an MLIP foundation model, where the message-passing atomic cluster expansion (MACE) is taken as an example, based on the data collected from biased samplings along the reaction coordinate of interest with the Caracal program package. The reaction is first sampled with the foundation model at different temperatures, and then the sampling is repeated with the fine-tuned model until the errors of selected energies and forces with respect to the high-level reference method fall below a chosen threshold. In this paper, this method is benchmarked systematically by alternating the amount of collected training data and the MACE MLIP architecture, such that an optimal compromise between speed and accuracy can be obtained. To make a direct comparison of full-dimensional reaction rate constants between MLIP and the reference method possible for the first time, two gas-phase reactions with analytical potential energy surfaces from the literature have been chosen: The internal proton transfer in malonaldehyde and the proton exchange between methane and an OH radical. In both cases, nuclear quantum effects are considered by ring-polymer molecular dynamics (RPMD). In line with this, it has been observed that the explicit inclusion of recrossing trajectories in the training set becomes important for the accurate parametrization of reversible reaction mechanisms. The results show that it is possible to parametrize high-quality reactive MLIPs without the need to select reference data manually and with a limited number of expensive quantum mechanical reference calculations.

We investigate the thermodynamic and structural properties of divalent patchy hard rods confined to a one-dimensional channel by modeling the bonding sites as attractive square-well (SW) patches located at the rod tips. The zero-range sticky limit is recovered by letting the well width vanish while keeping the stickiness parameter finite. While Wertheim's first-order thermodynamic perturbation theory becomes exact in this sticky limit, it fails for finite-range site-site interactions. Because the present model is mathematically equivalent to an exactly solvable one-dimensional nearest-neighbor fluid, we use the exact solution to reformulate the thermodynamics in terms of association-theory variables, including the fraction of unbonded sites and a generalized law of mass action. Finite-range SW sites produce a richer structural behavior than sticky sites, including monotonic and oscillatory asymptotic decay of the pair correlation function, separated by the Fisher-Widom line. In the monotonic regime, the correlation length exhibits an absolute maximum defining the Widom line, while in the oscillatory regime, it may display a local maximum and minimum, whose locus defines the "Extrema of the Correlation length under Oscillatory decay" line. These features disappear in the sticky limit, where the system remains entirely in the oscillatory regime. We also show that the high-pressure behavior of the correlation length changes from ξ ∼ p2 for finite-range SW sites to ξ ∼ p3 in the sticky limit.

Humanistic and rights-based approaches emphasize dignity, autonomy, self-determination and meaningful participation in community life for adults with intellectual disabilities (ID). Yet, in many ID services, everyday support is often shaped by risk-averse routines, safeguarding responsibilities and normalization-oriented expectations, creating tensions between declared commitments and daily practice. This study focuses on a year-long residential volunteer programme in which Generation Z young adults live and volunteer alongside adults with ID in a residential community. Their close involvement in everyday life, combined with their absence of formal professional responsibilities, offers a unique vantage point for re-examining how autonomy, protection and expectations of progress are negotiated in everyday support. Using a qualitative design, the study drew on focus-group data collected over 6 months with 12 young volunteers aged 18-19 in a year-long residential programme within a professionally guided residential ID service. The discussions explored volunteers' reflections on everyday support relationships, autonomy, protection, social inclusion and the meanings they attributed to volunteering. Data were transcribed verbatim and analysed manually using reflexive thematic analysis. The findings are organized according to the study's three research questions. Volunteers perceived the goals of support as extending beyond functional independence towards authentic dialogue, supported challenge and a more flexible understanding of progress. They also described volunteering as a developmental encounter that reshaped their self-perceptions through vulnerability, responsibility and relational acceptance. Finally, they viewed social change as dependent on everyday exposure to people with ID, through which their presence becomes familiar, ordinary and less stigmatized. Volunteers' reflections offer a distinctive lens for examining how humanistic commitments are translated into everyday residential support. Their accounts illuminate the relational and ethical tensions involved in balancing autonomy, protection, normalization and expectations of independence. The findings suggest the value of strengthening reflective practice in ID services and of re-examining how 'progress' is defined in everyday support, beyond functional goals and standardized expectations.

Mathematical methodology-spanning statistics, time series analysis, modeling, and AI-driven approaches-functions as a foundational language of biomedical research rather than a mere instrument, profoundly shaping the field by extracting structure from complex biological data. Yet as these methods grow more sophisticated, a quieter problem emerges: when the reasoning encoded in our methods is not made readable, scrutiny becomes harder-it grows more difficult to separate signal from artifact, mechanism from correlation, or insight from overfitting. The capacity for such distinctions is not lost to us; rather, the controls that data science has developed to enforce them are applied unevenly, and the expectation that quantitative methods remain legible to their users has eroded. We term this the "magicalization" of mathematics-the transformation of quantitative methods into oracular pronouncements accepted on faith or incantations rejected wholesale, rather than transparent arguments open to challenge. We treat this less as an accomplished verdict than as a tendency whose costs compound if current practice fails to correct it. This departs fundamentally from the vision of Poincaré and Wiener, who held that mathematics must function as a shared language sustaining dialogue between quantitative and domain experts. We readily concede that achieving operational understanding of mathematical constructs across disciplinary boundaries is inherently difficult; yet abandoning mutual intelligibility is neither scientifically sound nor methodologically neutral-it limits scrutiny and obstructs mechanistic understanding. We trace how magicalization manifests in clinical translation, black-box deployment, and research evaluation; identify its structural causes in complexity escalation, incentive misalignment, and disciplinary siloing; and argue that recovering mathematical interpretability serves as more than an academic luxury-it stands as a prerequisite for rigorous, mechanistically grounded biomedical science.

Integrins are conserved cell-adhesion receptors implicated in development and disease, including joint disorders and osteoarthritis. Unlike humans, which encode 18 α- and 8 β-subunits, Drosophila melanogaster carries only 5 α- and 2 β-integrins, offering a simplified system to dissect their functions. While βPS is established as essential for embryonic muscle attachment, the roles of the less-characterised βν subunit, and the extent of overlap between the two, remain unresolved. Here, we combined βν null mutants with tissue-specific βPS knockdowns to systematically define their contributions to muscle function. We find that βν is required during early development, where its absence impairs larval body wall muscle performance, but becomes largely dispensable for adult survival, flight and other locomotory activities. By contrast, βPS is indispensable throughout Drosophila development, including the indirect flight muscle (IFM) integrity, where its depletion disrupts sarcomere organisation, precisely the H-zone width and downregulates thin filament genes. Notably, βν assumes supplementary roles in muscle development, with its transcript levels getting lowered when βPS is compromised. Again, in the functionally compromised larval muscles of βν nulls, βPS transcript levels are lowered, but gets upregulated in the functionally fit βν null adult muscle subsets. The results suggest, βν might function as a modulatory component of the integrin network rather than an essential determinant of IFM development. These findings uncover distinct yet cooperative functions of βPS and βν in Drosophila muscle development, providing a framework to understand how integrin diversity contributes to muscle performance.

Alternative polyadenylation (APA) generates mRNA isoforms with distinct 3' untranslated regions (3'UTRs), thereby influencing transcript stability and translation. In cancer, 3'UTR shortening can activate oncogenes by escaping microRNA (miRNA)-mediated repression, but its role in hepatocellular carcinoma (HCC) remains poorly defined. Here, we profiled mRNA length alterations in multistage human HCC transcriptome datasets and investigated their functional consequences. Approximately 77% of mRNAs with altered length exhibited 3'UTR shortening. Glypican-3 (GPC3) was the most prominently upregulated shortened transcript, and high GPC3 expression was associated with poor prognosis in HCC. GPC3 knockdown reduced proliferation and induced apoptosis, whereas GPC3 overexpression promoted cell growth. Among APA regulators, Cleavage Stimulation Factor 2 (CSTF2) was upregulated in HCC, correlated positively with GPC3 expression, and predicted adverse clinical outcomes. Modulation of CSTF2 expression altered GPC3 3'UTR length, with CSTF2 overexpression promoting GPC3 3'UTR shortening, increasing GPC3 protein expression, enhancing proliferation, and suppressing apoptosis. Further analysis revealed that GPC3 3'UTR shortening removed binding sites for miR-96-5p and miR-140-5p, relieving miRNA-mediated translational repression. These findings identify CSTF2-driven APA as a mechanism of oncogenic GPC3 activation in HCC and suggest the CSTF2-GPC3 axis as a potential therapeutic target. Liver cancer is one of the leading causes of cancer-related death worldwide. Glypican-3 (GPC3) is often highly increased in liver cancer and is being studied as a marker and treatment target, but the reason for its increase is not fully understood. In this study, we analyzed patient datasets, liver cancer cells, and tumor samples to investigate how GPC3 is controlled. We found that liver cancer cells often produce a shortened form of GPC3 RNA. This shorter RNA form avoids regulation by small RNA molecules that normally help keep GPC3 levels low. We also identified CSTF2 as an important factor that promotes this shortening process. As a result, GPC3 becomes more stable and more highly expressed, helping cancer cells grow and survive. These findings reveal a new way that liver cancer cells increase GPC3 and may support future strategies to diagnose or treat liver cancer.

The role of allogeneic hematopoietic cell transplantation (alloSCT) in chronic lymphocytic leukemia (CLL) has decreased in recent years due to the emergence of new effective targeted agents for the treatment of this disease. However, for a certain group of heavily pretreated or high-risk CLL patients with no other therapeutic options, allo-SCT remains important. Due to the fact that in most high-risk CLL patients it is possible to achieve durable response as a result of Bruton's tyrosine kinase inhibitors (ВТК), BCL-2 inhibitor and especially in their combined application, including in the first line of therapy, the choice of time point for alloSCT becomes relevant. In this retrospective study allo-SCT was performed in 44 patients with the period from 2006 to 2023. Progression-free survival was 79.2% at 12 months and 69.3% at 24 months. Similarly, overall survival was 81.4% at 12 months and 74% at 24 months. Graft-versus-host disease relapse-free survival was 57%. Despite small sample size, our study demonstrates that alloSCT has become a significantly safer procedure in patients with CLL.

HIV case management supports people living with HIV to be linked to and retained in care. HIV case management becomes virtual case management (VCM) when some or all these services are provided via virtual tools or platforms including mobile phones, chat messenger apps, other mobile or web apps, and/or electronic case management systems. The COVID-19 pandemic accelerated the use and expansion of virtual services, including health services, across the globe. These case studies document how HIV programs in Indonesia and Nepal transitioned from in-person case management to VCM during the COVID-19 pandemic in 2020. As part of this transition, the program in Nepal implemented VCM in 37 districts that were providing services to 12,820 people living with HIV (PLHIV), and in Indonesia the program supported 18,244 PLHIV in 5 districts. Data on the transition from in-person support to VCM were collected on client clinical outcomes, costs of the virtual services, and case manager feedback. These case studies indicate that VCM is a feasible and affordable approach to implement in low- and middle-income country contexts. Between March and September 2020, 10,995 (82.1%) and 3,801 (51.5%) PLHIV in Nepal and Indonesia, respectively, were supported by VCM. Continuity of care remained high in both countries with only 1%-2% interruptions in treatment. Viral load suppression also remained high in both countries (91%-92% in Indonesia and 94%-95% in Nepal). Viral load coverage, however, was low, but this was influenced by clinic and laboratory closures. Startup costs were low (<US$2,500), and the monthly cost per person to provide VCM was $2.34 in Nepal and $4.67 in Indonesia. Case manager feedback was focused on compensation, expanded reach of virtual services, gaps in client mobile phone ownership or digital literacy, efficiency of services, and confidentiality and privacy. VCM has transformative potential to expand the reach of health services and provide differentiated options, meeting clients' preferences and needs. The experiences and lessons learned from these two case studies can guide the implementation of future VCM programs in other countries.

This commentary examines the widening gap between evidence generation and the pace of innovation in medicine. New algorithms emerge before their predecessors have been validated, most never reaching the evidence required to justify their use. The gap is sharpest in critical care, where sepsis and acute respiratory distress syndrome exemplify a field that has multiplied predictive models without seeing them enter routine practice. Evidence takes years to build; by the time it arrives, clinical reality has changed: populations, co-interventions, and standards of care no longer match those in which evidence was produced. Our evidence hierarchies were designed for a world that held still long enough to be captured. Algorithmic velocity outpaces validation; models are trained on cohorts that have drifted by deployment. As personalization pushes stratification toward the single patient, conventional proof becomes untenable. The challenge is epistemologic: how we conceive, produce, and sustain proof in medicine.

In this work, we employed neural network potentials (NNPs) to accelerate the conformational exploration of poly-glycine, poly-alanine, and poly-sarcosine up to hexapeptides at the M06-2X/6-311+G(d,p) level. One methodological advance is that, for penta- and hexapeptides, only single-point DFT calculations (energies and forces) are sufficient to train NNPs to achieve an accuracy of approximately 4 kJ mol-1. With these accurate NNPs, we efficiently identified low-energy (<25 kJ mol-1) minima for all 12 peptides. Based on the structures of these low-energy conformers, we found that: (1) the relative stability of the zwitterionic form increases consistently with peptide size. Among these peptides, the zwitterionic form becomes the global minimum only for hexa-sarcosine. (2) N-methylation shows a strong propensity to stabilize cis-peptide bonds. Tri-, tetra-, and hexasarcosine preferentially adopt cis-peptide configurations. By comparison, C&#x3b1;-methylation plays a less significant role. Interestingly, tetra- and hexaalanine are more likely to adopt cis conformers compared to penta-alanine, which has recently been studied experimentally via IR-VUV spectroscopy. The DFT-optimized coordinates of all 12 peptides can serve as a useful reference for validating our theoretical results against future experimental IR studies.

As the global demand for soil pollution control becomes increasingly urgent, innovative material application strategies are essential for remediating soils co-contaminated with chromium (Cr) and cadmium (Cd) by efficiently immobilizing heavy metal ions and promoting their stabilization. This study evaluated humic acid-loaded nanoscale zero-valent iron (nZVI@HA) for the remediation of Cr- and Cd-contaminated soil. The remediation performance and underlying mechanisms of nZVI@HA were systematically investigated through soil incubation experiments, metal speciation analysis, high-throughput sequencing, and quantitative real-time PCR. nZVI@HA achieved immobilization efficiencies of 58.19% for available Cr and 35.84% for available Cd. On day 50 of remediation, exchangeable Cr and Cd were markedly transformed into residual, Fe-Mn oxide-bound, and carbonate-bound fractions, substantially reducing their mobility and bioavailability. Concurrently, nZVI@HA alleviated Cr(VI) and Cd(II) stress, increased microbial community diversity, and improved soil fertility. The enrichment of taxa associated with ChrA, CzcA, and NitR suggests that nZVI@HA may enhance microbial resistance to Cr(VI) and Cd(II), potentially contributing to Cr and Cd immobilization. The immobilization mechanisms primarily involved chemical reduction, adsorption, ion exchange, and microbially mediated processes. The synergistic effects between nZVI@HA and soil microorganisms make nZVI@HA an efficient and environmentally benign remediation material, providing an effective strategy for treating soils co-contaminated with heavy metals.

We recently showed that 65% of medical specialists' guidelines in the context of chronic disease management in the Netherlands contain recommendations on lifestyle. However, it remains unclear how these recommendations are perceived and implemented in clinical practice. To analyse (1) the level of implementation of these recommendations and (2) the knowledge, attitudes and needs to further facilitate the implementation of lifestyle recommendations in chronic disease management within specialist care from both patient and healthcare professional perspectives. Mixed-methods cross-sectional study using two surveys. Hospital care in the Netherlands. Medical specialists affiliated with the Dutch Association of Medical Specialists (n=193) and patients who had visited a medical specialist within the previous 6&#x2009;months, recruited via the Dutch Patient Federation (n=1057). Lifestyle recommendations embedded in clinical practice guidelines for chronic disease management. The level of implementation is assessed by the self-reported frequency of lifestyle discussions and familiarity with lifestyle recommendations in clinical practice guidelines. Patients and medical specialists report different levels of implementation. While 72% of medical specialists reported discussing lifestyle topics during consultations, only 37% of patients recalled such discussions. Guideline familiarity among medical specialists was significantly associated with applying lifestyle advice in clinical practice (Fisher's exact test, p=0.02). Both groups expressed positive attitudes toward addressing lifestyle as part of medical specialist care consultations. Although medical specialists considered the lifestyle recommendations applicable, they identified key factors for successful implementation, including the framing of recommendations, patient motivation and capacity to make lifestyle changes and the organisational and societal contexts in which lifestyle recommendations are delivered. Although both medical specialists and patients recognise the importance of addressing lifestyle in healthcare, implementation in clinical practice can still be improved. Strengthening implementation requires institutions to allocate adequate resources to support these consultations, including protected time, targeted training and clearly defined referral pathways. Broader societal and political commitment, ensuring that prevention becomes a priority and shared responsibility across the healthcare ecosystem.

The endoplasmic reticulum (ER) is the primary site for the synthesis and folding of membrane and secretory proteins, which together comprise a large fraction of the total protein output in mammalian cells. Striated muscle cells contain a specialized membrane system, the sarcoplasmic reticulum (SR), which regulates calcium homeostasis and contraction. However, the biochemical and physiological relationship between the ER and SR, as well as the extent to which both compartments contribute to protein synthesis, remain incompletely understood. Quantification of ER- and SR-associated proteins in isolated ventricular cardiac myocytes revealed that the relative abundance of ER/SR-resident protein quality control components and ribosomes decreased during postnatal maturation, whereas SR-associated Ca2 +-handling proteins increased. Immunocytochemistry revealed that the membrane compartment prominent in early postnatal stages exhibits predominantly ER characteristics and diminishes during postnatal development. In adult cardiac myocytes, the SR becomes the dominant membrane network throughout the cell, while ER markers remain enriched in the perinuclear region. Immunocytochemistry further indicated that the ER and SR perform overlapping yet distinct specialized functions, with excitation-contraction coupling localized to the SR, and initiation of secretion concentrated within the ER. In adult ventricular cardiac myocytes, ribosomes and mRNA localize adjacent to both the ER and SR, indicating their roles as direct sites of localized protein synthesis and homeostasis. These findings demonstrate that molecular differentiation and structural organization of the ER/SR during cardiac muscle development culminate in a specialized protein synthesis network within the sarco/endoplasmic reticulum of adult myocytes. KEY POINTS: Although the sarcoplasmic reticulum (SR) is the established centre for calcium regulation in striated muscle, its role in membrane and secreted protein synthesis has remained unknown. It has remained unclear whether the endoplasmic reticulum (ER) and SR coexist as distinct membrane networks in cardiac myocytes or whether they form a single system that fulfills both calcium-handling and protein synthesis functions. We found that postnatal cardiac maturation involves a major reorganization in which the centralized, ER-dominant network of neonatal myocytes is replaced by an expansive, SR-dominant network in the adult cell periphery, while ER markers become largely confined to the perinuclear region. Using stimulated emission depletion super resolution microscopy and electron microscopy, we demonstrated that active ribosomes and mRNA associate with the longitudinal SR but are spatially excluded from ryanodine receptor 2-rich junctional zones. Our results establish that the SR functions as a specialized, distributed protein synthesis network that enables adult cardiac myocytes to maintain their highly organized cellular architecture through localized translation.