共找到 20 条结果
The genetic diagnostic armamentarium includes a host of different genetic tests, each with their own set of indications, resolution, coverage, diagnostic utility and limitations. It is essential for all medical practitioners to have some basic knowledge about the principles, indications and interpretation of these tests. This position statement of the Society for Indian Academy of Medical Genetics (SIAMG) provides guidelines and recommendations regarding the use of cytogenetic and molecular cytogenetic tests in clinical practice.
Cancer-related cognitive impairment (CRCI), a common side effect of cancer and its treatment, is characterised by difficulties in memory, attention and executive function. This qualitative sub-study was part of a single-site, parallel-group, pilot randomised controlled trial in which recruitment and retention exceeded our expectations. The aim was to explore participants' experience and motivation for sustained engagement with a web-based cognitive rehabilitation (eReCog) intervention amongst people with aggressive lymphoma who were self-reporting cognitive decline. We used an inductive qualitative approach, conducting semi-structured interviews with fourteen participants. Interviews were recorded, transcribed and a reflexive thematic approach was used to describe and interpret key themes and sub-themes in the data. Fourteen interviews were completed. We extracted four themes describing participants experience and motivation for sustained engagement with eReCog. These included information needs, experience of participation, support and ease of use. Participants were motivated to engage to gain knowledge and strategies to manage their CRCI symptoms; they enjoyed the experience and felt validated via the online community created. Finally, they valued the additional support they received and appreciated the convenience and flexibility of the web-based program. Our findings show that engagement with eReCog was driven by perceived cognitive improvements, psychosocial benefits and accessibility. Addressing both cognitive and psychosocial needs is warranted in web-based rehabilitation to foster continued participation engagement. Web-based cognitive rehabilitation interventions should enhance accessibility and earlier integration into the cancer trajectory to optimise long-term survivorship care in people with haematological cancers should be considered. Australian New Zealand Clinical Trials Registry ACTRN 12623000705684 on 30th June 2023.
The central problem in heart failure with reduced ejection fraction (HFrEF) is reduced contractility. Existing inotropes are associated with adverse effects. In this exploratory study, we aimed to assess the safety and tolerability of AC01, a novel oral calcium-sensitising inotrope and ghrelin receptor agonist, in patients with HFrEF. In this phase 1b/2a, randomised, double-blind, placebo-controlled study, adults aged 18-80 years with heart failure for at least 6 months and an ejection fraction of 40% or lower were enrolled at 14 sites in the Netherlands, the UK, Sweden, and Italy. All patients had a transvenous implantable cardioverter defibrillator for primary prevention, with back-up pacing to protect against excessive bradycardia. Other eligibility criteria included sinus rhythm or permanent, persistent, or paroxysmal atrial fibrillation or flutter (only allowed in phase 2a), with a mean resting heart rate of 55-90 beats per min. Randomisation used permuted blocks, with block sizes of four for phase 1b and three for phase 2a. In phase 1b, patients were enrolled in four sequential dose cohorts and randomly assigned 3:1 to ascending doses of AC01 (0·1 mg, 0·3 mg, 1·0 mg, or 3·0 mg) or placebo twice daily for 7 days. In phase 2a, patients were randomly assigned 1:1:1 to parallel groups receiving 1·0 mg AC01, 3·0 mg AC01 (1·0 mg AC01 on days 1 and 2 and 3·0 mg thereafter), or placebo orally twice daily for 28 days. Patients, study personnel, outcomes assessors, those analysing the data, and the sponsor were masked to treatment assignment. The primary outcome was safety and tolerability. Safety was monitored by physical examination, vital signs, safety laboratory assessments, and 12-lead electrocardiograms (ECGs) periodically during the treatment period and until the end-of-study visit (day 12 in phase 1b and day 42 in phase 2a), and cardiac rhythm was continuously monitored remotely using a patch device until day 9 in phase 1b and until day 4 in phase 2a. Adverse or unexpected events, signs, or symptoms were recorded. This study is registered with ClinicalTrials.gov, NCT05642507, and has been completed. Between Feb 23, 2023, and Aug 28, 2025, 58 patients (53 [91%] male and five [9%] female patients with a median age of 66·0 years [IQR 60·3-72·0]) were randomly assigned: 32 in phase 1b and 26 in phase 2a. In phase 1b, four cohorts of eight patients were enrolled; in each cohort, six patients were allocated to AC01 and two to placebo, with AC01 dose cohorts of 0·1 mg, 0·3 mg, 1·0 mg, and 3·0 mg. In phase 2a, nine patients were allocated to 1·0 mg AC01, eight to 3·0 mg AC01, and nine to placebo. There were 12 AC01-related adverse events in phase 1b and 18 in phase 2a. There were no AC01-related serious adverse events; one treatment-related serious adverse event of increased high-sensitivity cardiac troponin I concentration occurred in a patient receiving placebo in phase 1b. Mild or moderate treatment-emergent adverse events were reported in 33 (80%) of 41 patients receiving AC01 and 12 (71%) of 17 patients receiving placebo. The most common treatment-emergent adverse events were hypotension, non-sustained ventricular tachycardia, dyspnoea, hyperglycaemia, dizziness or vertigo, and headache. ECG data showed no apparent signs of tachycardia, new-onset tachyarrhythmias, myocardial ischaemia, or morphological or conduction abnormalities. No case of symptomatic hypotension was reported, and there were no apparent effects of AC01 on high-sensitivity cardiac troponin I or NT-proBNP. There were no deaths during the study. In patients with HFrEF, AC01 over 28 days appeared safe and well tolerated, and no major harms were identified in this early-phase study. These findings support further investigations of AC01 in larger studies. AnaCardio.
Peptides have emerged as pivotal agents in biomedicine due to their exceptional physicochemical properties, including high binding affinity, minimal immunogenicity, and precise target specificity. This review critically examines recent advancements in peptide-based strategies for pancreatic disorders, encompassing inflammatory conditions (e.g. pancreatitis), metabolic dysfunctions (e.g. diabetes), and notably, pancreatic cancer. We delineate the evolution of peptide therapeutics, emphasizing rational drug design approaches such as backbone cyclization and N-methylation to enhance metabolic stability, complemented by computational methodologies like molecular docking and AI-driven affinity maturation to optimize target engagement. The discussion highlights key innovations, including peptide probes for early diagnostic detection and peptide-drug conjugates for targeted intervention, while evaluating their efficacy in preclinical models and assessing their biosafety profiles. Furthermore, we survey current clinical trials aimed at translating these engineered peptides into clinical applications. Concluding with a perspective on precision medicine, we outline future trajectories necessitating advanced AI-integrated design frameworks and robust clinical validation to accelerate the bench-to-bedside translation of peptide technologies.
The development of executive function continues in adolescence, a phase bringing independence to choose behaviors and environments. In parallel, compromised executive function may foster unhealthy eating behaviors and weight gain. However, obesity-related differences in executive function in adolescents remain poorly understood. In this systematic review and meta-analysis, we investigated whether executive function is compromised in adolescent obesity and whether any executive function domain (inhibition, cognitive flexibility, working memory, decision-making, planning and verbal fluency) shows more pronounced impairments than others. Pooled across executive function domains, results from 49 studies (n = 9648 participants) that compared adolescents with excess weight (defined as overweight or obesity) to healthy-weight peers on at least one executive function task, showed a small effect indicating worse performance in adolescents with excess weight (g = -0.314, p <.001, 95% CI [-0.413, -0.214]). To disentangle the effects of obesity and overweight, we performed separate analyses which indicated similar differences for adolescents with obesity, but not for those with overweight, compared to healthy-weight peers. We found no evidence of selective executive function impairments, as effect sizes for performance differences between weight groups did not differ between domains. Samples with higher age, BMI range and proportion of female participants showed more pronounced differences between weight groups. In conclusion, our results show that adolescents with obesity scored modestly but consistently lower on executive function tasks compared to their healthy-weight peers, with moderating effects of age, BMI and sex. Our findings raise implications for future studies and the treatment of obesity.
Muscle contractions to control prosthetic hands do not feel like those to control natural hands because amputation decouples movement sense (kinesthesia) from movement execution. The myokinetic kinesthetic interface (MKkI) uses remote vibration of permanent magnets implanted in amputated forearm muscles to restore kinesthesia. A participant reported coordinated finger movements of hand closing and opening, constrained within physiological bounds, with stereotypical conformations and dynamics. Aggregated unstructured explorations and systematic psychophysics exposed unreported perceptual sensitivity at vibration frequencies that trigger kinesthetic sensations. Complex coordinated grip sensations elicited from single forearm muscles reveal that kinesthetic brain representations are likely rooted in perception of synergistic movement production. By leveraging the natural synergistic features of kinesthesia, the MKkI will help link perception and action to functionally elevate emerging intuitive bidirectional human-machine interfaces.
The quest for knowledge has led to longstanding investigations into its sources. The foundation in information (data, evidence) is a cornerstone for the delineation of knowledge from belief or conviction. Through the execution of occurrences in the world, information flow is generated, which is observable and measurable in conceptual space with Lyapunov exponents and information dimensions. All occurrences have causes, which precede their effects, temporally and mechanistically. After much debate over the nature of cause-effect relationships, consensus has evolved, which interprets causation as the transfer of a preserved property (energy or momentum). This transfer modifies the thermodynamic entropy in closed and open systems alike. Independently, time progression has been characterized as being rooted in a transfer of heat (energy). Thus, causation is the driver of both, changes in thermodynamic entropy and time progression. It also effectuates a measurable evolution of information. With the acceptance of these interpretations, the underpinning of knowledge finds a unique definition. The essential causation of occurrences begets an information evolution, which-if observed in the process of scientific inquiry-serves as a basis for the generation of knowledge. Information flows not observed become lost to human access through dissipation in time and entropy.
Care models integrating geriatrics into primary care are emerging across Ontario. Referred to as Primary Care Integrated Geriatric Teams (PCIGTs), their evidence-based approaches improve access to specialized care and support for older adults. Seven Ontario models were highlighted through webinars held in spring 2025, attended by nearly 200 participants. Presenters and participants identified promising design features, key learnings and supports needed to advance goal-aligned care for older adults. Relevant to primary care transformation, health system redesign and policy efforts in Ontario and beyond, PCIGTs can support primary care attachment, reduce pressure on acute services and promote aging in place.
Although cognitive performance typically appears preserved in far-from-onset Huntingtin Gene Expansion Carriers (HGECs), underlying neuropsychological mechanisms may be subtly altered and remain undetected. Practice effects from repeated task exposure provide a sensitive measure of cognitive adaptability, with early disruptions signalling reduced neural efficiency before standard deficits emerge. This study aimed to examine longitudinal practice effects across annual neuropsychological testing in far-from-onset HGECs and to identify the disease burden threshold where these patterns diverge. Data from 2777 HGECs and 2777 age-matched controls were drawn from the ENROLL-HD cohort across five annual assessments. Longitudinal cognitive trajectories were modelled using linear mixed-effects models, adjusting for demographics. Segmented regression models identified disease burden thresholds marking the onset of practice effect attenuation. Quartile-based stratification assessed the influence of genetic burden. An internet-based Practice Effects Trajectories Calculator (PE-TraC) was developed to model normative longitudinal distributions across tests and visualize individual-level trajectories. HGECs showed reduced practice effects in tasks involving processing speed and executive function, with divergence from controls emerging by Year 2. Segmented regression identified the earliest disease burden breakpoint in Stroop Word Reading Task (249.6) and the latest in the Symbol Digit Modalities Test (291.9). Quartile (Q) analyses showed that participants with the highest genetic burden (Q4) exhibited minimal or absent practice effects, Q3 showed delayed decline, and Q1-Q2 followed similar trajectories to controls. Reduced practice effects constitute a sensitive marker of early cognitive dysfunction in far-to-onset individuals. These findings support the inclusion of dynamic cognitive measures in far-from-onset HGECs trials as potential endpoints.
Ambient artificial intelligence (AI) scribe technology is entering clinical settings with the promise of reducing documentation burden. For health system leaders, these tools pose governance challenges rather than simple information technology upgrades. Early pilots show reductions of up to 30% in after-hours charting, but results vary with implementation quality. This article argues that Canada should classify AI scribes as Class II Software as a Medical Device and outlines governance questions for executives and boards. By treating ambient AI scribes as strategic leadership priorities - rather than technology deployments - healthcare leaders can balance efficiency with ethical stewardship and strengthen patient trust.
Placental growth factor (PLGF) drives cardiomyogenesis and vasculogenesis during cardiogenesis. Here, we present a protocol for enhancing production of human pluripotent stem cell (hPSC)-derived cardiomyocytes (CMs) and endothelial cells (ECs). We describe steps for CM-/EC-directed hPSC differentiation with PLGF. Our approaches can achieve production of hPSC-CMs/-ECs by 2- to 2.5-fold compared with those in traditionally established protocols, through promoting proliferation and differentiation of cardiac and vascular progenitors. For complete details on the use and execution of this protocol, please refer to Witman et al.1.
Recent progress has brought benchmarking of (heuristic) quantum algorithms at scale within reach. Particularly in combinatorial optimization, it is key to empirically analyze and track progress towards quantum advantage. This work introduces a systematic, fair and comparable benchmarking framework for quantum optimization methods by presenting ten model-independent problem classes that are challenging for classical methods. Track records of specific instances and solutions are given in an accompanying open-source repository. While the individual properties of the problem classes vary, they all become challenging from less than 100 to, at most, an order of 100,000 decision variables. We reference results from state-of-the-art solvers for instances across all problem classes and demonstrate exemplary baseline results obtained with quantum solvers for selected problems, which illustrate standardized benchmark reporting. The presented problem instances may be approached with classical or quantum algorithms executed on varying hardware platforms to drive the field towards quantum advantage.
This research introduces a novel technique for early prediction of cardiac affliction in ECG imagery. The initial phase involves pre-processing using an Adaptive Wiener Filter. Subsequently, segmentation is performed utilizing a Modified Fuzzy C-Mean to isolate distinct components of the ECG signal. The next crucial step involves feature extraction deploying Gray Level Co-occurrence Matrix, enabling the capture of texture and spatial dependencies. The classification stage, utilizes Hybrid Sparrow-Chicken Swarm Optimized Deep Convolutional Neural Network, tailored to optimize the deep learning model. The execution with the Python software, achieves 98.5% precision in the detection of cardiac afflictions from ECG imagery.
暂无摘要（点击查看详情）
To synthesize and consolidate the existing evidence on the use and characteristics of Free/Libre and Open Source Software (FLOSS)-based electronic health records (EHRs) in global healthcare settings. We conducted an overview of reviews, systematically searching 14 information sources using a peer-reviewed strategy. Pairs of reviewers independently and in duplicate screened studies, extracted predefined data items, and assessed methodological quality. Findings were synthesized thematically and categorized by use and system characteristics. Nine systematic reviews (2012-2024) met the inclusion criteria. Methodological quality was generally low. We identified 26 themes related to use and 19 related to system characteristics. FLOSS-based EHRs were predominantly implemented in low- and middle-income countries, driven by cost advantages, adaptability, and community support. Reported challenges included organizational barriers, uncertainties about the capacity of volunteer-led development communities, limited comparative evidence with proprietary systems, and concerns over set-up, customization and training costs. System characteristics varied, especially regarding interoperability, security, and governance. The implementation of FLOSS-based EHRs appears to be influenced more by institutional and organizational factors than by technical features. Their adaptability supports use in resource-limited settings, but persistent challenges may raise concerns about long-term sustainability. To realize the potential of FLOSS-based EHRs, stakeholders must strengthen institutional readiness and governance structures, while the research community must improve the methodological quality of supporting evidence.
In reverse total shoulder arthroplasty (rTSA), glenoid component inclination critically influences complications and implant performance. Current literature predominantly advocates for neutral or 0° inclination referenced to the supraspinatus fossa in order to avoid superior tilt which may lead to loosening. However, the influence of resting scapular rotation (RSR) on the effectively obtained inclination relative to the global reference system (gravity) remains poorly defined. This study aims to address this gap by evaluating the impact of RSR on global glenoid component inclination following rTSA. This retrospective cohort included 93 consecutive patients who underwent rTSA with 3D preoperative planning and patient-specific instrumentation (PSI) for baseplate placement targeting 0° inclination. Standardized pre- and postoperative true anteroposterior radiographs were obtained with a vertical plumb line aligned to gravity. Measured parameters included scapular rotation angle (SRA), humeral abduction resting angle (HARA), scapulohumeral abduction resting angle (S-HARA), glenoid inclination angle (GIA), global glenoid inclination (GGI), and arthroplasty scapulohumeral abduction resting angle (AS-HARA). Interrater reliability was assessed using intraclass correlation coefficients (ICC). The effect of preoperative RSR on postoperative GGI was evaluated. Correlations among radiographic parameters and associations with clinical outcomes at 9 and 26 weeks were analyzed using multiple regression. Interrater reliability for the measured parameters was excellent (ICC=0.953-0.989). SRA varied widely from 14° upward rotation to 42° downward rotation with a mean of -15±9°. Three reproducible SRA types were identified, which remained mostly constant postoperatively. Despite a targeted glenoid inclination angle of 0°, GGI differed significantly with a mean of -18±10° and a range from 1 to -53° (p<0.0001) and demonstrated a strong correlation with SRA (r=0.77). Preoperatively, S-HARA averaged 113±10° and HARA 7±8°; postoperatively, S-HARA 117±10°, HARA 7±8°, and AS-HARA 116±10°. At 9 weeks, higher postoperative AS-HARA and S-HARA were associated with better ASES Index Scores, whereas by 26 weeks patients had recovered regardless. Preoperative RSR varied substantially across the cohort. Consequently, the effective postoperative global glenoid component inclination ranged from downward to superior inclination depending on the scapula rotation angle, despite targeted glenoid inclination angle of 0° executed with PSI. Therefore, accounting for scapula rotation in terms of the global glenoid inclination when planning the glenoid component inclination seems warranted. The consistency of SRA before versus after rTSA allows its incorporation into personalized planning to avoid superior inclination in the global reference system, which may increase shear forces on the glenoid component and lead to a slower recovery.
The thymus is a primary lymphoid organ where antigen-presenting cells (APCs) orchestrate the development of a self-tolerant and functional T-cell repertoire. Herein, we elucidate the pivotal role of thymic selection defects in autoimmune pathogenesis and evaluate targeted therapeutic strategies for these mechanisms. This review synthesises recent advances in understanding how cortical thymic epithelial cells (cTECs), medullary thymic epithelial cells (mTECs), dendritic cells (DCs), and B cells collaboratively mediate positive and negative selection. cTECs drive positive selection through thymus-specific antigen processing machinery, including the β5t-containing thymoproteasome and cathepsin L, which generate self-peptide-MHC complexes with moderated affinity. mTECs broadly express tissue-restricted antigens (TRAs) under the control of AIRE, establishing a foundational self-antigen landscape for central tolerance. DCs execute efficient clonal deletion via cross-presentation and antigen transfer, while B cells contribute to tolerance against soluble antigens through BCR-mediated uptake. We further quantify the relative contributions of these APC subsets during thymic selection and discuss how defects in these processes underlie autoimmune diseases and immunodeficiencies. Finally, we highlight emerging therapeutic strategies that target thymic selection mechanisms, including AIRE modulation, tolerogenic DC vaccines, and thymic tissue engineering. These insights not only advance our understanding of T-cell development but also offer novel avenues for immune reprogramming in disease.
Cloud computing is a key enabler of modern computing services, offering scalability and flexibility. However, efficient management of cloud resources remains challenging due to limited capacity and the increasing number of tasks requiring timely execution. An effective task scheduling strategy is therefore essential to improve resource allocation and utilization, reduce operational costs and energy consumption, and support high availability-especially for long-term jobs. In this paper, we propose a new scheduling approach that combines a Social-Based Algorithm (SBA) with Deep Reinforcement Learning (DRL), referred to as SBA-DRL. This method allocates tasks to resources by learning from workload patterns and adapting to workload characteristics in a batch scheduling context. We evaluate SBA-DRL using both a synthetic dataset and the real-world Google Cloud Jobs (GoCJ) under workloads ranging from 200 to 1,000 tasks. On the synthetic dataset, our method reduces cost by 20.21% and energy consumption by 25.31%, while improving resource utilization by 9.36%. On the GoCJ dataset, it achieves up to 28.94% lower cost, 8.16% less energy use, and a 14.04% increase in resource utilization. In both cases, SBA-DRL also demonstrates better performance in resource allocation and high-availability management compared to existing heuristics, meta-heuristics, hybrid, and machine learning-based schedulers. These results indicate that the proposed SBA-DRL approach effectively addresses key challenges in cloud task scheduling, offering a practical solution to enhance the efficiency and sustainability of cloud systems.
To evaluate early patient-reported outcome measures (PROMs), radiographic alignment changes, intraoperative laxity changes and complications in a retrospective series of constitutional valgus knees treated with robotic-assisted total knee arthroplasty (TKA) using an intentional asymmetric balancing strategy and a semi-personalized (SP) alignment technique. This retrospective single-centre cohort included consecutive patients with end-stage valgus osteoarthritis (OA) and constitutional valgus morphotypes (coronal plane alignment of the knee III/VI) treated with imageless robotic-assisted TKA and a minimum follow-up of 12 months. The balancing workflow intentionally accepted mild residual lateral laxity. Medial and lateral compartment laxity (mm) were quantified intraoperatively at 0° and 90°. PROMs (Knee Society Score [KSS] and Forgotten Joint Score [FJS]), range of motion (ROM) and hip-knee-ankle angle (HKA) were assessed preoperatively and at the latest follow-up. Complications were recorded. Fifty-eight patients were included at a mean follow-up of 26.5 ± 15.0 months. KSS Knee improved from 58.3 ± 9.4 to 87.9 ± 11.0 (mean change +29.6 points, 95% confidence interval [CI] = 26.0-33.2; p = 0.00002) and KSS Function from 58.8 ± 15.0 to 82.4 ± 15.7 (mean change +23.6 points, 95% CI = 18.8-28.4; p = 0.00004). Flexion contracture improved from 3.9 ± 4.0° to 0.6 ± 1.2° (mean change -3.3°, 95% CI = -4.3 to -2.3; p = 0.00010), while flexion increased from 101.4 ± 6.0° to 126.8 ± 8.6° (mean change +25.4°, 95% CI = 23.2-27.6; p = 0.00001). HKA improved from 6.2 ± 4.5° valgus to 2.1 ± 1.8° valgus (mean change -4.1°, 95% CI = -5.2 to -3.0; p = 0.00030). Lateral laxity decreased in extension from 4.5 ± 1.7 to 2.5 ± 1.3 mm (mean change -2.0 mm, 95% CI = -2.7 to -1.3; p = 0.001) and at 90° from 5.3 ± 2.0 to 1.9 ± 1.2 mm (mean change -3.4 mm, 95% CI = -4.3 to -2.5; p = 0.0008), with smaller medial reductions. Post-operative complications occurred in four patients (6.9%) (deep vein thrombosis, transient peroneal neuropraxia, superficial wound issue and one manipulation under anaesthesia); there were no pulmonary emboli, periprosthetic joint infection or revision procedures. In this retrospective single-surgeon series of constitutional valgus knees treated with robotic-assisted TKA, intentional asymmetric balancing was associated with good early clinical outcomes, correction towards less valgus alignment, and a reproducible reduction in lateral laxity, with a low complication rate. These findings support the feasibility of this measurable laxity-guided strategy, but do not establish superiority over alternative balancing philosophies. Level III, retrospective cohort.
Clinical data exchange remains fragmented and insufficient to support coordinated, safe care. Decades of technological progress, standards development, and interoperability-focused legislative and regulatory improvements have been incremental, underscoring the need for unifying initiatives to coordinate and improve operations and outcomes. We sought to identify persistent barriers limiting clinical data interoperability. We propose a coordinated, time-bound U.S. "moonshot" initiative to create a unified canonical clinical terminology ("SuperSNOMED") and catalyze rapid refinement and streamlined adoption of Fast Healthcare Interoperability Resources (FHIR) and Implementation Guides (IGs) to accelerate safe, high-fidelity data exchange. We synthesized insights from an expert roundtable; conducted additional expert discussions; appraised peer-reviewed published and online evidence on standards, interoperability policies, and developing regulations; and then identified barriers to interoperability implementation. We then developed recommendations for policy, legislative, and regulatory changes. We identified five barrier domains: fragmented terminology standards and value sets; multiple overlapping data exchange standards with uneven FHIR adoption; incomplete or misaligned certification and policy incentives; variable interpretation and implementation of IGs; and insufficient funding and support for standards development. We propose a national program including three coordinated pillars: SuperSNOMED, a well-governed, rapidly maintained, canonical terminology integrating major domains and mappings; FHIR acceleration converging on a minimum set of IGs and certified legacy-data transforms during a transition window; and policy and governance for certification criteria, incentive alignment, and funding a paid expert task force to execute an ambitious 3-year plan. Certification and workforce incentives with transitional data-quality safeguards such as reconciliation-on-first-use for transformed historical data would catalyze high-impact interoperability beyond existing EHR regulatory programs, clinical information systems, and knowledge bases critical to health care. Interoperability remains fragmented despite progress. This state-of-the-art paper is a call to action for a focused, funded, well-governed national moonshot effort to unify terminology and streamline exchange standards.