Search Results (850)

Background: Gastrointestinal (GI) cancers, particularly colorectal, gastric, and liver cancers, account for a major global burden of incidence and mortality and remain important targets for genetic susceptibility research. Long non-coding RNAs (lncRNAs) can regulate gene expression and are increasingly studied in carcinogenesis. Numerous case–control studies have investigated associations between lncRNA polymorphisms and cancer risk, but findings are inconsistent. This study systematically evaluated the association between lncRNA single nucleotide polymorphisms (SNPs) and GI cancer susceptibility. Methods: A systematic literature search from Embase, Medline, Scopus, and Web of Science databases identified 174 potentially extractable studies. Eligible studies were case–control or cross-sectional studies published up to 8 May 2026; case reports, reviews, and meta-analyses were excluded. After screening for identical cancer type, identical SNP, and sufficient statistical data, only variants supported by at least three independent case–control studies were eligible for meta-analysis. Seven SNPs across six lncRNAs, comprising 23 studies (15,131 cases and 20,969 controls), were selected. Because of the limited number of eligible studies, subgroup analyses could not be performed consistently. Odds ratios (ORs) with 95% confidence intervals (CIs) were assessed under allelic, dominant, and recessive genetic models using fixed- or random-effects models according to heterogeneity. Results: In the primary analyses restricted to homogenous Chinese populations, H19 rs3024270 was significantly associated with hepatocellular carcinoma under allelic (OR = 1.22, 95% CI: 1.05–1.42, p = 0.01) and dominant models (OR = 1.22, 95% CI: 1.03–1.45, p = 0.02). Exploratory analyses including mixed populations identified additional associations, with the strongest observed for MEG3 rs7158663 and colorectal cancer, showing significant risk elevation under allelic (OR = 1.42, 95% CI: 1.25–1.63, p < 0.00001), dominant (OR = 1.42, 95% CI: 1.20–1.68, p < 0.0001), and recessive models (OR = 1.98, 95% CI: 1.46–2.68, p < 0.0001). PRNCR1 rs16901946 showed a significant association with gastric cancer under the dominant model (OR = 1.20, 95% CI: 1.02–1.41, p = 0.03), while GAS5 rs145204276 demonstrated a recessive-model association with gastric cancer (OR = 1.30, 95% CI: 1.16–1.46, p < 0.0001). In contrast, GAS5 rs145204276 in colorectal cancer; H19 rs2839698 and MALAT1 rs619586 in hepatocellular carcinoma yielded heterogeneous or unstable pooled estimates. Findings should be interpreted cautiously due to the limited number of studies, heterogeneity, and potential publication bias. Conclusions: Among the primary analyses, H19 rs3024270 showed the most consistent association with HCC susceptibility. Exploratory analyses identified candidate variants, including MEG3 rs7158663, PRNCR1 rs16901946, and GAS5 rs145204276. Population-specific effects and study heterogeneity remain important limitations. PROSPERO registration number for this study: CRD42023389742. Full article

The indoor microbiological contaminants present in the built environment, including residential buildings, can pose significant risks to human health and well-being and the sustainability of indoor environments. Therefore, the total aerobic microbial count (TAMC) and total yeast and mold count (TYMC) are key indicators used to evaluate microbial contamination levels in indoor spaces. This study presents an assessment of TAMC and TYMC in residential indoor environments in two cities in Spain, Pamplona and Seville, which represent different climate zones, with Seville characterized by extensive air conditioning use due to its high summer temperatures. We conducted sampling and analysis in 20 dwellings over two summer campaigns to quantify microbial populations and identify parameters that worsen TAMC and TYMC and promote amplification (I/O, indoor/outdoor). The results show that ventilation type, building design, and climatic conditions significantly influence indoor bacterial amplification. The study indicates that the implementation of the Spanish building code in 2006 has improved microbial Indoor Air Quality (IAQ), even in airtight and energy-efficient dwellings, highlighting the importance of integrating ventilation and health considerations into sustainable building design. Environmental parameters such as temperature and CO₂ concentration were reliable indicators of bacterial proliferation. Kitchen design and the presence of pets also emerged as relevant determinants of microbial loads. Overall, the use of I/O ratios proved effective for identifying indoor microbial amplification, supporting their application in future IAQ assessments, sustainable building evaluations, and healthy housing strategies. Full article

Background/Objectives: Chronic obstructive pulmonary disease (COPD) is increasingly viewed as a disorder of impaired cellular adaptation to chronic stress, involving oxidative injury, mitochondrial dysfunction, and accelerated cellular senescence. We investigated whether genetic variation in these pathways contributes to disease susceptibility, lung function impairment, and polygenic risk prediction. Methods: Thirty-three single-nucleotide variants were analysed in 747 patients with COPD and 703 controls. Associations with disease susceptibility and lung function parameters were assessed using regression models with correction for multiple testing. Weighted and unweighted polygenic scores were constructed from associated variants and evaluated using receiver operating characteristic and net reclassification improvement analyses. Results: Significant associations were identified in genes involved in antioxidant defence (NFE2L2, HMOX1, GSR), PI3K/AKT/mTOR signalling (PIK3R1, PTEN), mitochondrial function (TOMM40), cellular stress responses (FOXO3A), and long non-coding RNA regulation (MEG3, CDKN2B-AS1). The strongest association was observed for PIK3R1 rs831125 (OR = 2.31, p = 2.53 × 10⁻¹⁰). Variants in NFE2L2, PIK3R1, MEG3, MALAT1, and SIRT3 were additionally associated with pulmonary function parameters. The weighted polygenic score demonstrated good discriminative ability (AUC 68.8%, 95% CI 65.9–71.7%) and substantially improved prediction when combined with age, sex, and smoking exposure (AUC 88.1%, 95% CI 86.3–89.8%; NRI = 0.62, p = 2.21 × 10⁻²⁸). Conclusions: The identified loci converge on interconnected pathways involved in cellular stress adaptation, mitochondrial homeostasis, and senescence, supporting their contribution to chronic obstructive pulmonary disease susceptibility and functional decline. Full article

Decentralized Autonomous Organizations (DAOs) enable blockchain-based collective governance, yet existing studies often evaluate DAO governance through isolated mechanisms, particularly voting systems. This narrow view does not sufficiently explain recurring problems such as governance capture, weak accountability, inadequate safeguards, and inefficient resource allocation. This paper proposes a Layered Governance Coverage Model that conceptualizes DAO governance as a system of seven interdependent institutional functions spanning participation, agenda formation, collective choice, safeguards, execution, incentives, and meta-governance. The model uses a four-level strength scale to assess not only whether governance functions are present, but also how strongly they are institutionalized. It is empirically applied to thirty-seven active DAOs through evidence-based coding of publicly available governance artifacts. The results show that governance breadth does not necessarily imply governance maturity: collective choice and execution mechanisms are more developed than accountability, safeguards, and meta-governance. Beyond DAO-native settings, the paper positions governance maturity as a trust and resilience regime for blockchain-based IoT and AI infrastructures, where governance affects security, reliability, data integrity, and risk oversight. The paper discusses AI-enabled governance analytics as a support mechanism for monitoring governance activity, detecting anomalies, and improving governance observability. The proposed framework contributes a structured approach for evaluating and designing resilient governance architectures in DAOs and blockchain-based IoT/AI systems. Full article

Digital resilience has become an increasingly important concept in information systems research due to growing dependence on digital infrastructures, escalating cyber threats, and the emergence of regulatory frameworks that formalize resilience obligations. This study provides a systematic literature review of how digital resilience is conceptualized, operationalized, and aligned with emerging European Union (EU) regulatory frameworks. Following PRISMA 2020 guidelines, a systematic search was conducted across Scopus, Web of Science, and IEEE Xplore databases. Fifty-three peer-reviewed studies published between 2006 and 2026 were analyzed using a structured analytical coding framework capturing conceptual clarity, dimensional structure, methodological maturity, and regulatory alignment. The results reveal significant conceptual fragmentation across the literature. While governance, ICT risk management, incident response, and third-party risk management emerge as recurring resilience dimensions, definitional and structural convergence remains limited. Measurement approaches are dominated by maturity models and qualitative assessment frameworks, with relatively few studies proposing validated indicator-based models. Regulatory alignment with EU frameworks such as the Digital Operational Resilience Act (DORA) and the Network and Information Security Directive (NIS2) remains partial and inconsistent. The study identifies a structural alignment gap between regulatory resilience requirements, conceptual resilience models, and operational measurement approaches, providing a foundation for developing regulator-compatible digital resilience assessment frameworks. Full article

Although climate change is increasingly recognized as a material risk for firms, the extent to which climate-related risks are operationally integrated into enterprise risk management (ERM) processes remains unclear. This article presents a structured literature review to answer the question of how firms have integrated climate risk assessment, considering both physical and transition risks, into ERM processes. Following the PRISMA 2020 protocol, 22 published articles from Web of Science and Scopus, published between 2018 and 2026, were included in the review. Articles covering financial institutions, as well as policy-only and sectoral-only studies, were excluded. The articles were screened through five eligibility criteria: firm-level focus, governance, risk assessment, climate risk management and/or ERM, and type of climate risk. All articles were assessed by two researchers to reduce bias, and Cohen’s kappa was calculated. Following coding and qualitative analysis, the findings indicate that firms have advanced governance structures, disclosure practices, and analytical assessment tools for climate risk assessment, while operational integration into ERM systems remains limited. Results also reveal persistent integration gaps, including strategic–operational disconnection, temporal and methodological mismatches, symbolic implementation, and systemic and knowledge barriers. These challenges constrain the effective translation of climate risk information into risk management practices and strategic planning. Overall, the study, based only on academic literature, concludes that climate risk integration is still incomplete and weakly embedded within ERM systems. In the expanding regulatory landscape, particularly with IFRS S2, the study provides a baseline for understanding current firm-level practices and future developments in climate risk integration at the academic level. Full article

Background/Objectives: Obstructive sleep apnea (OSA) and related sleep disorders affect a substantial proportion of hospitalized patients, with an estimated 48% pooled prevalence of undiagnosed OSA in cardiac inpatients and up to 80% of moderate-to-severe community OSA cases carrying no formal diagnosis at the time of hospital admission. In parallel, frailty—a state of heightened physiological vulnerability arising from cumulative multi-system biological decline—is present in 40–80% of inpatients and shares deep, bidirectional neurobiological pathways with sleep-disordered breathing through circadian dysregulation, intermittent hypoxia, hypothalamic–pituitary–adrenal axis activation, and chronic low-grade inflammation. Despite this convergence, no prior study has integrated validated, administratively computable frailty phenotyping with a machine learning framework specifically designed to predict inpatient sleep disorder diagnosis—and OSA in particular—at the point of hospital admission. The present study addresses this gap by developing an admission-time, explainable machine learning framework for the prediction of inpatient sleep disorder diagnoses (ICD-10 G47.x, encompassing OSA G47.3, insomnia G47.0, hypersomnia, and circadian rhythm disorders) and of insomnia specifically (ICD-10 G47.00). Methods: We developed and evaluated a suite of five binary classification models—XGBoost, Random Forest, LightGBM, CatBoost, and Decision Tree—using 9682 balanced hospitalization episodes from the MIMIC-IV (version 2.2) database. The predictor set comprised 23 admission-time structured features across three domains: (i) frailty and comorbidity burden, including the Hospital Frailty Risk Score (HFRS) derived from ICD-10 codes, the Elixhauser comorbidity index, prior admission history, and six binary disease flags (obesity, hypertension, type 2 diabetes, heart failure, COPD, and depression/anxiety); (ii) physiological and laboratory biomarkers from the first 24 h of care, including minimum SpO₂, heart rate variability, hemoglobin, creatinine, albumin, and arterial blood gas parameters; and (iii) sociodemographic and administrative variables encompassing age, sex, ethnicity, insurance type, and admission acuity. Model performance was assessed through five-fold stratified cross-validation and bootstrap confidence intervals (n = 1000 iterations), with predictor importance quantified using SHapley Additive exPlanations (SHAP). Results: XGBoost achieved the strongest aggregate performance across all evaluation metrics, attaining an area under the receiver operating characteristic curve (AUC) of 0.871 (95% CI: 0.856–0.887), accuracy of 79.6%, F1-score of 0.820, and sensitivity of 94.9%, correctly identifying 903 of 952 true positive cases in the held-out test set; all gradient boosting frameworks substantially outperformed the Decision Tree baseline (AUC 0.836). SHAP analysis identified the HFRS and Elixhauser index as the two dominant predictors, followed by depression/anxiety, obesity, hypertension, and minimum SpO₂—a hierarchy that recapitulates the canonical clinical phenotype of obstructive sleep apnea in frail inpatients rather than that of primary insomnia, indicating that the model is preferentially capturing the OSA–frailty axis within the broader G47.x outcome. The predicted probability outputs were well-calibrated across all risk deciles. Conclusions: Frailty-derived features, in combination with admission-time clinical and physiological data, can predict inpatient sleep disorder diagnoses—predominantly OSA—with high sensitivity and well-calibrated risk estimates. The deployable, interpretable nature of the XGBoost model makes it directly suitable for integration into clinical decision support systems, offering a screening tool that requires no dedicated instrumentation beyond routine admission data. By flagging high-risk patients at the moment of admission, the framework provides a concrete mechanism for accelerating referral for definitive diagnostic confirmation (overnight oximetry, polysomnography) and earlier initiation of CPAP and related therapies, with direct implications for reducing the persistent diagnostic gap, perioperative risk, and preventable adverse outcomes in frail hospitalized populations. Full article

Background: Cardiovascular diseases (CVDs) remain the leading global cause of mortality, yet a critical “translational gap” persists: Conventional biomarkers often fail to detect subclinical stages or predict individual disease trajectories. While single-omics studies have proliferated, the field lacks a unified framework synthesizing these molecular layers with advanced computational intelligence. Aim: This review addresses this gap by evaluating the synergistic integration of multi-omics and Artificial Intelligence (AI) to transition from descriptive markers toward predictive precision cardiology. Scope: Evidence from non-coding RNA networks (miRNAs, lncRNAs) and exosomal trafficking is synthesized alongside a critical assessment of Machine Learning (ML) architectures, including supervised, unsupervised, and deep learning (DL) models. Findings: Unlike traditional reviews, this work delineates the specific pipelines required to deconvolute high-dimensional signatures—such as TMAO, acylcarnitines, and cardiac-enriched miRNAs—into actionable risk models for heart failure (HF) and post-infarction outcomes. The primary barrier to clinical translation is identified not as data scarcity but as the lack of standardized bioinformatic workflows and model interpretability. Conclusions: This review distinguishes itself by proposing an integrated molecular–computational framework that prioritizes Explainable AI (XAI) and standardized multi-omic protocols. Such a shift is essential to bridge the gap between high-dimensional biological insights and routine clinical decision-making. Full article

The cryopreservation of pre-implantation embryos has become routine in medically assisted reproduction (MAR), and the proportion of frozen embryo transfers has steadily increased in recent years. Because cryopreservation through either slow-cooling protocols or ultra-rapid vitrification requires potentially cytotoxic cryoprotective agents to prevent uncontrolled and detrimental ice crystal formation, the safety of these procedures must be carefully considered. Evidence from human epidemiological studies, including retrospective and prospective controlled studies, and data from national patient registries indicate that children born after frozen embryo transfer have a higher birth weight than those born after spontaneous conception and have an increased risk of rare genomic imprinting disorders, such as Beckwith–Wiedemann, Silver–Russell, or Prader–Willi syndrome. Encompassing not only reversible DNA methylation patterns established during gametogenesis, but also the timed abundance and availability of transcripts and proteins required to establish or maintain epigenetic marks throughout development and differentiation, as well as persistent or transient post-translational histone modifications and non-coding RNAs, the epigenome may be particularly sensitive to cryopreservation. Importantly, epigenetic regulation is highly complex. Alterations of the epigenome at any developmental stage are often not monocausal, do not necessarily result in immediate disturbances in the pre-implantation embryo, and are unlikely to operate through simple all-or-nothing mechanisms; however, they may have long-lasting effects at later developmental stages. To make matters even more complex, differences between species in terms of epigenetic regulation or lineage differentiation are well known and translation from animal model systems to humans must be considered with caution. More recently, epigenetic regulation by non-coding RNAs has also come into focus, as these molecules are crucial, either directly or indirectly, for gene expression, translation, and protein biosynthesis during development. Therefore, assessing potential adverse effects of cryopreservation on the entire epigenome remains a major challenge, particularly because little is known about indirect factors, such as post-translational histone modifications and non-coding RNAs. In this review, we focus on the potential influence of the cryopreservation of pre-implantation embryos on the epigenetic profile in humans and animals. Specifically, we consider DNA methylation of imprinted genes and global DNA methylation; post-translational histone modifications; the abundance and availability of transcripts and proteins required to establish, maintain, or protect epigenetic patterns; and the presence of non-coding RNAs involved in epigenetic control. Full article

The holistic assessment of building life cycles requires integrating economic, environmental, and social dimensions, including occupational risks and cost management. However, building maintenance planning is often treated separately from sustainability assessment and construction cost classification systems. This study proposes a methodology that integrates maintenance and repair budgets with sustainability evaluation through a unified coding structure linking construction and maintenance work units. The approach combines economic cost analysis, environmental footprint indicators (carbon, water, energy, and ecological footprints), and occupational risk assessment within a life cycle framework. The methodology incorporates prevention through design by analyzing ergonomic and safety risks associated with construction work units and predicting future risks throughout the building’s service life. The structure has four phases: temporal planning of interventions, classification and coding of work units, impact analysis using sustainability indicators, and synthesis of results in a maintenance planning model. The data is integrated in a database using an exchange format compatible with sustainability analysis tools and BIM environments. The methodology is applied through a case study of social housing in Andalusia. Results show that maintenance interventions can be connected to construction work units in the assessment of the three dimensions. Full article

Suicidal mental imagery are self-generated images of injury and death experienced across a range of mental health conditions, but also experienced in people who have no diagnosable mental health condition. For some, these images can be quite distressing and unwanted, but for others, these mental pictures serve to bring comfort and problem-solving capabilities. From a clinical and research perspective, they are not fully understood and are underexplored. Suicidal mental imagery is a known risk factor for attempted suicide due to imagery’s amplification and habituation effects, potentially moving a person from imagining suicide to acting on it. This paper presents a taxonomy of the different types of suicidal mental imagery from first-hand accounts extracted from phase one of a two-phase qualitative study called the suicidal mental imagery (SUMI) study. This taxonomy of imagery types is drawn from fifteen semi-structured interviews exploring imagery experiences in adults from Ireland. The characteristics of these images were analysed qualitatively using an Interpretive Description approach, with the resulting taxonomy developed through additional analytic processes informed by cognitive behavioural therapy (CBT) principles and a priori coding. The taxonomy, therefore, illustrates experiences from a rich dataset under distinct categories to improve our understanding of the key mechanisms underpinning suicidal mental imagery for practice, helping to assist open dialogue in imagery assessment to better inform suicide prevention interventions. Full article

Importance: A comprehensive analysis of childhood cancer and cancer predisposition syndromes (CPSs) incidence can provide insights that lead to improvements and modifications in treatment protocols through personalized therapy, thereby reducing toxicity. Purpose: This study aimed to analyze age-specific hospital-based childhood cancer rates and the distribution of CPSs in a 20-year pediatric cohort from the region. Materials: A total of 2190 patients, aged from birth to 17 years, diagnosed with any type of neoplasm classified by ICD-10 codes at Karol Jonscher’s Clinical Hospital of Poznan University of Medical Sciences (KJCH PUMS) between 1 January 2000, and 31 December 2019, were included, with 193 (8.8%) having an underlying CPS. Results: The pediatric population of the Greater Poland Region has declined over the past two decades. The most common diagnoses can be grouped into three main categories: (1) leukemias, involving 704 patients (32.1%); (2) central nervous system (CNS) tumors, represented by 382 children (17.4%); and (3) lymphomas, including 279 patients (12.7%), together accounting for 1353 cases (61.8%). The age-specific hospital-based case rate for childhood cancer (all types combined) peaked in the 0–28 days age group at 71.8 per 100,000 person-years (95% CI: 52.2–96.4), with a trend to decrease with age and a slight increase among adolescents aged 16–17 years (13.6 per 100,000, 95% CI: 12.0–15.4). The age-specific incidence of CPS-positive cancers declined from 18.0 (95% CI: 8.2–29.4) per 100,000 person-years in the first month of life to 0.7 (95% CI: 0.3–1.2) in 16–17-year-olds. CPS-positive children were diagnosed at significantly younger ages for four cancer types: liver and intrahepatic bile duct tumors (C22: A = 0.097, adjusted p < 0.001), myeloid leukemia (C92: A = 0.179, adjusted p < 0.001), lymphoid leukemia (C91: A = 0.309, adjusted p = 0.007), and renal tumors (C64: A = 0.335, adjusted p = 0.013). Conclusions: CPSs likely play a significant and underestimated role in pediatric cancers, especially during early childhood. Improving access to genetic testing could greatly enhance risk assessment, personalized treatment, and long-term outcomes in pediatric oncology. Full article

Earthquakes pose a serious threat to urban areas located in seismically active regions, particularly in developing countries where rapid urbanization and weak enforcement of building regulations increase the vulnerability of the built environment. Pakistan is highly exposed to seismic hazards due to its tectonic setting, and many residential buildings are constructed without adequate seismic design considerations. Therefore, assessing building vulnerability and understanding community perception of earthquake risk are essential for effective disaster risk reduction. This study investigates the relationship between the structural vulnerability of residential buildings and earthquake risk perception among residents in Peshawar, Pakistan. Two contrasting urban settlements were selected as case studies: WAPDA Town, representing a planned residential area, and Hashtnagri, representing an older unplanned settlement. A total of 400 buildings were surveyed through field investigations. Seismic vulnerability was assessed using the Rapid Visual Screening (RVS) method based on structural characteristics such as building age, number of floors, construction materials, structural irregularities, construction quality, and presence of seismic reinforcement features. A Physical Vulnerability Index (PVI) was developed to categorize buildings into different vulnerability levels. In addition, a questionnaire survey was conducted to evaluate earthquake risk perception among residents, and a risk perception index (RPI) was calculated. The results indicate that buildings located in the unplanned settlement exhibit significantly higher seismic vulnerability compared to those in the planned residential area due to poor construction practices, irregular structural configurations, and the absence of seismic-resistant features. Statistical analysis further reveals a positive relationship between physical vulnerability and earthquake risk perception, suggesting that residents living in structurally vulnerable environments tend to perceive higher earthquake risk. The findings highlight the importance of integrating structural vulnerability assessment with community awareness and preparedness programs. Implementation of seismic design provisions and improved enforcement of construction regulations, such as those specified in the Building Code of Pakistan 2022, can significantly reduce earthquake risk in rapidly growing urban areas. However, the present study did not directly evaluate the level of enforcement or compliance with the Building Code of Pakistan 2022 in either WAPDA Town or Hashtnagri. Therefore, the policy recommendations are intended as general implications derived from the observed vulnerability patterns. Full article

Pumping stations serve as the foundation platform for large-scale vertical fluid machinery, and their structural dynamics directly govern the vibration levels and long-term reliability of the installed pump units. In low-head vertical pumping stations, the interaction among the massive underwater substructure, flexible above-ground powerhouse, and surrounding backfill soil creates a complex dynamic system whose behavior remains insufficiently characterized. This study presents a comprehensive dynamic analysis of a large-scale vertical pumping station using a high-fidelity three-dimensional finite element model that incorporates the powerhouse superstructure, submerged concrete substructure, and backfill soil. Modal analysis under four boundary condition scenarios—varying in soil participation and interface contact conditions—systematically quantifies the influence of soil–structure interaction on natural frequencies and mode shapes. Resonance verification against three primary excitation sources—rotational frequency (4.917 Hz), blade passage frequency (24.583 Hz), and rotor–stator interaction frequency (196.667 Hz)—is extended from the first 50 modes to the 400th mode to assess potential high-order resonance risks. Results show that the roof slab, with its large span and low stiffness, exhibits the highest vibration susceptibility. For the rotational frequency, modes 4–12 fall below the 20% code-specified safety margin but rapidly exceed the threshold thereafter. For the blade passage frequency, the separation ratio decreases progressively with increasing mode order within the first 50 modes, and the extended analysis up to the 400th mode shows that the separation ratio remains well above 20% throughout modes 51–400. Consequently, no substantial resonance risk exists for the blade passage frequency within the entire computed range. The rotor–stator interaction frequency remains safely separated with margins exceeding 95%. These findings demonstrate the profound influence of soil–structure interaction and confirm that, despite a decreasing trend in frequency separation at higher orders, the blade passage frequency poses no substantial resonance risk up to the 400th mode. This work provides a rigorous analytical framework for vibration-informed design and optimization of pump foundation systems, with direct implications for the reliability and operational safety of large-scale vertical fluid machinery. Full article

This article analyses the Italian Legislative Delegation Bill of 4 September 2025 (DDL 2025), which proposes the recontextualization of healthcare liability through the introduction of Article 590-septies into the Italian Criminal Code (c.p.) and the amendment of Article 590-sexies c.p. and of Articles 5 and 7 of the Gelli-Bianco Act (Law No. 24/2017). The study examines the extent to which the reform, if enacted, would produce a shift of criminal negligence liability from the individual frontline clinician towards the apex management figures of healthcare organizations—at both the corporate and hospital levels—and under what conditions such a shift would be compatible with the constitutional principle of personal criminal responsibility (Art. 27 Const.) and with the evidentiary criteria for criminally relevant omission. Adopting a doctrinal and jurisprudential analysis approach, the study formulates a falsifiable hypothesis, accompanied by four ex post verifiability indicators observable over a five-year time horizon following the possible entry into force of the provision. The analysis demonstrates how the DDL 2025 would recontextualize the notion of culpa—encompassing imperizia (lack of skill), negligenza (negligence), and imprudenza (imprudence), functionally comparable to forms of criminal negligence in common law systems—by linking fault assessment to contextual factors such as organizational deficiencies and resource scarcity. This approach would adopt a deflationary framework, establishing a distinction between avoidable human error and errors caused by systemic dysfunctions and foreshadowing a potential shift of liability towards apex management, who are required to ensure organizational models adequate to patient safety. This orientation, far from constituting a doctrinal novelty, would formalize ex lege a trajectory already established in civil and criminal case law of the Court of Cassation (Cass. No. 6386/2023, “Travaglino”), further intersecting with the administrative liability regime for organizations under Legislative Decree 231/2001. Significant interpretive challenges remain, related to the application of criminal liability criteria to the omissive conduct of healthcare managers, as well as to the contrasting international evidence on the behavioural effectiveness of medical liability reforms. The redefinition of top-management liability would therefore be configured not merely as a tool for the protection of the individual professional but as a derived constitutional guarantee of the right to health and the safety of care, pursued through formalized risk governance, the integration of incident reporting and organizational audit systems, the transition towards Enterprise Risk Management models, and the traceability of apex decision-making processes. Examples drawn from other European jurisdictions illustrate the heterogeneity of legal approaches to medical fault and frame the Italian proposal as a context-specific solution that nonetheless could contribute to the international debate on institutional and organizational accountability for patient safety. Full article