Growth retardation, particularly in weight-for-age, is a pervasive concern among preterm infants. It serves not only as a marker of immediate health status but also predicts long-term neurodevelopmental and metabolic outcomes. The decline in weight-for-age z-score reflects the discrepancy between an infant’s weight and the standardized population mean, adjusted for age. A decline exceeding 1.0 SD is a clinical red flag indicating suboptimal growth, commonly associated with inadequate nutritional support or underlying morbidities within the NICU stay. This study doesn’t merely document this problem; it ventures further by implementing a strategic quality improvement (QI) initiative tailored to the distinctive challenges faced in smaller NICUs, which often grapple with limited resources and less specialized staff compared to their larger counterparts.

At the heart of the intervention lies an evidence-based framework focusing on optimizing nutritional strategies – a critical determinant of neonatal growth. The team led by Morris, Liu, and Hetherton systematically assessed current feeding protocols and identified multifaceted barriers impeding optimal nutrition delivery. These barriers included inconsistent timing and quantity of feed initiation, variable use of fortifiers in breast milk, and delays in transitioning from parenteral to enteral feeds. Recognizing these limitations, they deployed protocol revisions grounded in current scientific literature emphasizing early aggressive nutrition as a cornerstone for mitigating growth failure in this vulnerable demographic.

The methodology embraced a multidisciplinary collaboration within the NICU teams, involving neonatologists, dietitians, nursing staff, and data analysts to foster an environment conducive to ongoing monitoring and rapid-cycle feedback. The team utilized Plan-Do-Study-Act (PDSA) cycles to iteratively refine feeding regimens and monitor growth parameters. These cycles allowed for dynamic adjustments tailored to individual infant responses, ensuring that nutritional goals translated into tangible anthropometric gains. This iterative, data-driven process is reflective of modern QI practices, underscoring a shift from rigid protocol adherence to agile, responsive care models.

Notably, the study also highlighted the underappreciated influence of real-time data analytics powered by health informatics systems. By integrating electronic medical record (EMR) data with growth tracking algorithms, the NICU teams could visualize trends and pinpoint infants at risk of significant growth faltering earlier in their hospitalization. This predictive capacity manifested as a form of precision medicine adapted to growth management, transforming aggregate data into actionable clinical intelligence that directly informed bedside care.

Beyond nutrition, the study shed light on the delicate interplay between growth and other clinical variables inherent to prematurity. Respiratory distress, intermittent infections, and enzymatic immaturity all conspire against optimal weight gain. The QI initiative incorporated rigorous protocols for managing these comorbidities, recognizing that nutritional interventions alone cannot surmount these barriers. Consequently, the comprehensive approach fostered resilience against the multifactorial insults that compromise neonatal growth trajectories.

The results were striking. After the implementation of the QI protocols, the proportion of infants discharged with a weight-for-age z-score decline exceeding 1.0 SD fell by approximately 20%, achieving the target set forth at the initiative’s inception. This reduction translates into meaningful improvements in the immediate and potentially long-term wellbeing of these infants, given the well-established links between early growth and developmental outcomes. Moreover, these gains were achieved without extending NICU length of stay or increasing complications, validating both safety and efficacy.

An integral component of this success was the tailored approach to resource limitation inherent in small NICUs. Unlike larger tertiary centers with dedicated lactation consultants and neonatal nutritionists, small NICUs often lack these specialized roles. The study demonstrated that structured education programs for existing staff coupled with simplified yet effective feeding algorithms could bridge this gap. This democratization of expert knowledge marks a pivotal advancement, setting a scalable precedent for similar institutions worldwide.

Further underscoring the importance of this study is the broader context of global neonatal health. Preterm birth remains a leading cause of infant mortality and morbidity globally, disproportionately affecting lower-resource settings where small NICUs are prevalent. The demonstrated efficacy of this QI intervention in small NICUs offers a beacon of hope. It articulates a practical, evidence-driven roadmap to ameliorate growth-related sequelae in preterm infants, a critical consideration for international neonatal health strategies aiming to reduce disparities.

In addition to the clinical outcomes, the study sparks renewed debate on standardized growth metrics in neonates. While weight-for-age z-scores are a widely accepted tool, the multifactorial nature of growth urges a multidimensional assessment framework incorporating length and head circumference to fully capture growth quality. The study’s focus on weight deficits remains an accessible and impactful starting point, yet it opens avenues for future research incorporating comprehensive anthropometric and functional outcomes.

The impact of these findings extends beyond neonatal units; pediatricians and developmental specialists caring for these infants post-discharge can anticipate a population with improved growth trajectories, potentially translating into more favorable neurodevelopmental profiles. Early-life growth deficits have been linked to cognitive impairments and metabolic syndromes, underscoring the critical window of NICU care in shaping lifelong health outcomes.

In synthesizing the technical and clinical aspects, this pioneering work by Morris et al. elegantly demonstrates that targeted quality improvement initiatives grounded in best practices, multidisciplinary collaboration, and robust data analytics can substantially improve critical outcomes for a high-risk population in resource-limited settings. Their success delivers a compelling model adaptable across diverse healthcare contexts, emphasizing that excellence in neonatal care is attainable beyond the confines of large academic centers.

This study serves as a clarion call to stakeholders encompassing healthcare providers, administrators, and policymakers to invest in scalable interventions that uplift the standards of care in smaller NICUs. Through enhanced training, protocol standardization, and data infrastructure improvements, the neonatal community can move towards equitable care delivering consistently better outcomes across all settings.

Moreover, the transparent reporting and rigorous evaluation framework featured in the study provide a blueprint for future quality improvement projects. The granular insights gleaned from this work exemplify the power of continuous quality improvement methodologies in driving substantive clinical change, reinforcing the crucial role of iterative learning cycles bolstered by real-time data feedback.

In closing, the 20% reduction in proportion of infants leaving NICU with suboptimal weight gain transcends a mere statistical achievement. It marks a transformative stride towards reshaping neonatal care paradigms, fostering healthier starts for moderate and late preterm infants with reverberating benefits into childhood and beyond. As the neonatal care community integrates these findings, the future portends a new era where growth faltering in preterm infants can be not only mitigated but potentially prevented at scale.

Subject of Research: Growth improvement in moderate and late preterm infants in small NICUs through quality improvement interventions.

Article Title: A quality improvement approach to growth in moderate and late preterm infants in small NICUs.

Article References:
Morris, M., Liu, J., Hetherton, M.C. et al. A quality improvement approach to growth in moderate and late preterm infants in small NICUs. J Perinatol (2026). https://doi.org/10.1038/s41372-026-02711-z

Image Credits: AI Generated

DOI: 18 May 2026

Preterm infants, defined as those born before 37 weeks of gestation, often experience significant respiratory distress due to underdeveloped lungs that lack sufficient surfactant to keep alveoli open. Resuscitation protocols currently involve the use of continuous positive airway pressure (CPAP) or mechanical ventilation, which includes the application of PEEP to prevent alveolar collapse and enhance gas exchange. However, the precise level of PEEP that balances efficacy with safety remains uncertain, leading to variability in clinical practice and outcomes. The POLAR trial aims to systematically investigate this critical parameter.

Developed by a multidisciplinary team led by Dr. Douglas G. Tingay and colleagues, the POLAR study protocol is designed as a randomized controlled trial—considered the gold standard for clinical evidence generation. This design will enable researchers to directly compare different PEEP levels applied during the resuscitation process. By rigorously controlling and measuring these variables, the study seeks to identify an optimal PEEP strategy that maximizes respiratory support while minimizing potential lung injury, such as volutrauma or barotrauma.

The scientific premise underpinning the POLAR trial is grounded in detailed pulmonary physiology. Positive end-expiratory pressure maintains airway patency and prevents cyclical alveolar collapse during exhalation. However, excessively high PEEP may overdistend delicate lung tissue, encouraging inflammation and subsequent chronic lung disease, a frequent complication known as bronchopulmonary dysplasia in preterm infants. Conversely, insufficient PEEP can lead to atelectasis and poor oxygenation, placing infants at risk for acute respiratory failure. Striking this balance is essential yet has remained elusive due to heterogeneous patient conditions and limitations in existing research.

What sets the POLAR trial apart is its real-time integration of cutting-edge respiratory monitoring technologies alongside clinical parameters. Detailed lung function assessments—including dynamic compliance and functional residual capacity—will be performed using non-invasive tools to tailor PEEP application and evaluate its immediate physiological impact. This approach reflects a paradigm shift from one-size-fits-all protocols toward personalized neonatal respiratory care, potentially reducing morbidity and mortality rates associated with prematurity-related respiratory distress.

Furthermore, the study embraces the complexities of neonatal adaptation at birth, recognizing that the transition from fetal to neonatal life involves major cardiopulmonary changes. In the womb, lungs are fluid-filled and remain unexpanded; however, upon birth, rapid clearance of fluid and lung expansion are essential for effective gas exchange. Appropriate PEEP levels during resuscitation can facilitate this transition by promoting alveolar recruitment and sufficient lung volume, critical for establishing stable oxygenation and ventilation.

Ethical considerations are meticulously addressed within the study design. The involvement of preterm infants—a population vulnerable due to their fragility—demands strict oversight and parent engagement. Informed consent processes and safety monitoring committees ensure the utmost adherence to ethical research standards, balancing scientific rigor with compassionate care. This ethical framework underscores the commitment to advancing neonatal medicine responsibly.

Anticipated findings from the POLAR trial promise to substantially influence clinical guidelines and practice worldwide. Many neonatal intensive care units (NICUs) follow varied protocols for initial respiratory support, often reflecting local preferences or limited evidence. By generating high-quality data on PEEP titration, the study aims to reduce inconsistencies, optimize resuscitation protocols, and establish evidence-based standards for care immediately after birth.

In addition to its clinical relevance, the POLAR study addresses broader global health implications. Preterm birth accounts for approximately 10% of all live births globally and remains the leading cause of neonatal mortality. Improving resuscitation strategies has the potential to save countless lives, especially in resource-limited settings where advanced respiratory support modalities are less accessible. Establishing simple, effective PEEP guidelines could therefore represent a cost-effective intervention with vast public health benefits.

The results of this trial will also contribute to the growing body of knowledge surrounding neonatal lung mechanics and pathophysiology. Such insights may fuel subsequent innovations in ventilatory support technologies, including the development of advanced ventilators designed specifically for the unique physiology of preterm infants. Moreover, understanding the interplay between ventilation pressures and lung injury pathways could open new avenues for pharmacological adjuncts aimed at protecting fragile lung tissue during postnatal adaptation.

Intriguingly, the POLAR research methodology incorporates a thorough follow-up phase to assess long-term developmental outcomes related to the initial resuscitation strategies. This is crucial as early respiratory interventions can have lingering effects on neurodevelopment and lung health throughout childhood. By correlating PEEP levels with these long-term outcomes, the study will aid clinicians in balancing immediate respiratory needs with future health considerations.

Another dimension to the POLAR trial is the interdisciplinary collaboration between neonatologists, respiratory therapists, biomedical engineers, and statisticians, highlighting the importance of diverse expertise in tackling complex medical challenges. Such teamwork ensures robust study design, precise data interpretation, and pragmatic translation of findings into bedside clinical practice, bridging the gap between scientific discovery and patient care.

The timing of the POLAR publication is particularly relevant given the ongoing advances in neonatal care and the increasing survival rates of extremely preterm infants. Despite these gains, respiratory complications remain a significant hurdle, often leading to extended NICU stays and elevated healthcare costs. By elucidating optimal PEEP strategies, this research could streamline clinical pathways, promote faster stabilization, and reduce the burden on healthcare systems.

As anticipation builds around the findings to emerge from this landmark trial, the neonatal community watches with hope for a new era of resuscitation excellence. The innovative approach of the POLAR study exemplifies how targeted clinical research can directly impact vulnerable populations, fostering better outcomes through evidence-based interventions.

In conclusion, the POLAR trial represents a milestone in neonatal respiratory care through its rigorous exploration of positive end-expiratory pressure during resuscitation of preterm infants. This study not only promises to refine critical clinical interventions at birth but also embodies a broader vision of precision medicine in neonatology, where individualized treatments enhance survival and quality of life for the most fragile patients. As healthcare providers await the full results, the potential for POLAR to transform frontline neonatal resuscitation protocols heralds an exciting future for preterm infant care.

Subject of Research: Exploration of optimal positive end-expiratory pressure (PEEP) levels during resuscitation of preterm infants immediately after birth.

Article Title: Positive end-expiratory pressure levels during resuscitation of preterm infants at birth (POLAR): study protocol for a randomised controlled trial.

Article References: Tingay, D.G., Galletta, L., Owen, L.S. et al. Positive end-expiratory pressure levels during resuscitation of preterm infants at birth (POLAR): study protocol for a randomised controlled trial. Pediatr Res (2026). https://doi.org/10.1038/s41390-026-04942-4

Image Credits: AI Generated

DOI: 10.1038/s41390-026-04942-4

Keywords: Neonatal resuscitation, positive end-expiratory pressure, preterm infants, respiratory support, pulmonary physiology, randomized controlled trial, neonatal intensive care, lung mechanics, bronchopulmonary dysplasia, precision medicine in neonatology

The impetus behind this pioneering work reflects the clinical urgency to devise effective prophylactic measures against Staphylococcus aureus infections, particularly in neonates weighing less than 1,500 grams at birth. These infants’ immune defenses are inherently immature, placing them at heightened risk for invasive bacterial diseases that can spiral into life-threatening conditions. Historically, GBS emerged as a formidable neonatal pathogen, yet efforts to mitigate its impact through targeted screening and intrapartum antibiotic prophylaxis have revolutionized perinatal care. The authors of this study propose extending the conceptual framework of GBS prevention to S. aureus, whose epidemiology and resistance patterns have complicated prevention attempts.

At the core of the model is a multi-layered approach that integrates maternal screening, colonization surveillance, and tailored antimicrobial stewardship within neonatal care protocols. Unlike GBS, which primarily affects neonates via vertical transmission during delivery, S. aureus exhibits a more complex transmission dynamic, involving both vertical and horizontal pathways, including environmental reservoirs within hospital settings. By elucidating these nuanced mechanisms, the researchers advocate for a comprehensive prevention paradigm incorporating molecular diagnostic tools capable of detecting colonization at early stages and guiding intervention.

The molecular biology of Staphylococcus aureus poses formidable challenges. Its ability to produce biofilms, evade host immune responses, and manifest multidrug resistance via mechanisms such as mecA gene-driven methicillin resistance demands innovative counterstrategies. The study underscores the applicability of rapid polymerase chain reaction (PCR) diagnostics adapted from GBS protocols to identify colonized neonates and mothers swiftly, enabling preemptive clinical actions. This is complemented by rigorous infection control practices bolstered by genomic surveillance, which tracks clonal expansions of virulent or resistant strains within neonatal units.

Immunologically, the work explores promising adjuncts to standard antimicrobial regimens, highlighting the potential of maternal vaccination to enhance passive immunity in neonates during the critical postnatal window. The vaccine candidates designed to target conserved surface proteins of S. aureus, similar to those exploited in GBS vaccine development, could mitigate neonatal colonization rates substantially. The study presents preliminary immunogenicity data and suggests pathways for accelerating clinical trials, emphasizing the need for global collaboration to standardize protocols and ensure equitable vaccine access.

In the context of neonatal pharmacology, the authors meticulously dissect the pharmacokinetic and pharmacodynamic considerations pertinent to antibiotic usage in very low birth weight infants. The delicate balance between therapeutic efficacy and toxicity is underscored, advocating for precision dosing guided by real-time drug monitoring. This precision medicine approach promises to enhance safety profiles while maintaining robust antimicrobial effects, thereby reducing incidences of necrotizing enterocolitis and antibiotic resistance emergence.

Equally transformative is the study’s elucidation of environmental decontamination strategies tailored to neonatal intensive care units (NICUs). Recognizing the propensity for S. aureus persistence on fomites and healthcare personnel’s hands, innovative disinfection protocols employing novel agents such as chlorhexidine-impregnated materials and ultraviolet light sterilization have demonstrated promising reductions in pathogen load. The authors call for integration of these technologies into routine NICU practice, supported by continuous education of healthcare workers on hygiene compliance.

A further striking feature of this research is its emphasis on data analytics and machine learning algorithms to predict infection outbreaks and identify high-risk neonates. By leveraging electronic health record data and microbiological surveillance, predictive models enable proactive management, thereby transforming infection control from reactive to anticipatory. Such technological integration represents a paradigm shift that transcends traditional microbiological techniques, paving the way for intelligent patient monitoring systems.

The ethical implications of implementing these multifaceted interventions receive thoughtful consideration in the article. The authors emphasize transparency, particularly in parental counseling regarding the risks and benefits of maternal screening and vaccination, as well as antibiotic exposure in neonates. Community engagement and interdisciplinary communication emerge as critical components to build trust and optimize uptake of preventive measures.

Furthermore, the model posits substantial economic benefits by reducing prolonged hospital stays, intensive antibiotic treatments, and sequelae of invasive infections. Cost-effectiveness analyses embedded within the study underscore the potential healthcare savings, which could be channeled into broader neonatal care improvements. Policymakers and healthcare administrators are encouraged to prioritize funding and resource allocation accordantly.

Importantly, the research sheds light on the global disparities in neonatal infection outcomes, advocating for tailored prevention programs that consider local microbial ecology and resistance profiles. Low- and middle-income countries, where resource constraints and high neonatal mortality persist, stand to gain immensely from adaptations of this model, facilitated by simplified diagnostic platforms and vaccine distribution networks.

This study not only bridges a critical knowledge gap but also catalyzes a call to action. The translation of GBS prevention strategies to the formidable challenge of Staphylococcus aureus in very low birth weight neonates embodies a synthesis of microbiology, immunology, clinical medicine, and public health. The holistic prevention model advances the neonatal care frontier, promising to transform outcomes for the most fragile lives at the very outset of existence.

In summary, the article by Minor et al. represents a landmark advancement in neonatal infectious disease prevention. By bridging foundational GBS insights to S. aureus management, it illuminates a path forward through molecular diagnostics, vaccination prospects, environmental hygiene innovations, and data-driven clinical care. As neonatal units worldwide grapple with the persistent menace of S. aureus, this comprehensive and scientifically rigorous model offers hope for a future where very low birth weight infants are shielded more effectively from infection-related adversities, with profound implications for survival and quality of life.

Subject of Research: Prevention strategies applying Group B Streptococcus models to combat Staphylococcus aureus infections in very low birth weight neonates.

Article Title: A model for prevention: applying lessons from Group B Streptococcus to Staphylococcus aureus in very low birth weight neonates.

Article References: Minor, A.A., Coggins, S.A., Sheffield, J.S. et al. A model for prevention: applying lessons from Group B Streptococcus to Staphylococcus aureus in very low birth weight neonates. J Perinatol (2025). https://doi.org/10.1038/s41372-025-02499-4

Image Credits: AI Generated

DOI: 27 November 2025

Neonatal pain assessment is notoriously complex due to the infants’ inability to verbally communicate their experiences. While various scales exist globally, the adaptation and validation of such tools for specific populations are indispensable. The researchers focused on neonates between 24 and 42 weeks of gestational age, representing a wide and vulnerable spectrum of newborn patients. Their primary goal was to establish whether the COMFORTneo-Brazil scale could effectively measure prolonged pain, thereby filling a gap in neonatal care within the Brazilian healthcare context.

The methodology employed was meticulous and involved multiple stages to ascertain the scale’s performance rigorously. Central to the study was the comparison of the COMFORTneo-Brazil scores with those obtained from the Échelle Douleur Inconfort Nouveau-Né (EDIN) scale, a recognized tool for neonatal pain assessment. By doing so, the research team sought to verify convergent construct validity—essentially confirming that these two distinct tools yielded statistically consistent results when evaluating similar pain parameters in neonates.

The study incorporated 133 evaluations on neonates, a sizeable sample that provides robustness to the statistical analyses undertaken. Two trained raters performed bedside assessments individually and subsequently conducted video assessments after a 10 to 14-day interval. This dual approach was strategic, aiming to evaluate both inter-rater and intra-rater reliability—the consistency of scores across different raters and over time by the same rater, respectively.

Statistical rigor was a hallmark of the research, utilizing Spearman’s correlation to gauge the strength of association between COMFORTneo-Brazil and EDIN scores. Impressively, the correlation coefficient, rho, was found to be 0.929 with a p-value less than 0.001, indicating a very strong and statistically significant relationship. These findings decisively support the convergent construct validity of the COMFORTneo-Brazil scale, confirming it as an effective instrument in the clinical evaluation of neonatal prolonged pain.

Beyond validity, reliability measures cemented the scale’s robustness. Intraclass correlation coefficients (ICC) surpassed the 0.9 threshold for both intra- and inter-rater reliability. Such high ICC values suggest that the scale produces consistent scores regardless of the rater or the timing of the assessment. This facet is essential in clinical practice; tools that yield variability can lead to misinterpretation of a neonate’s pain status and inappropriate care interventions.

The reliability was further corroborated by Bland–Altman analyses, a method that examines agreement between two measurement techniques or raters. The comprehensive application of this statistical technique ensured that differences in ratings were minimal and randomly distributed, which strengthens the confidence clinicians can place in the COMFORTneo-Brazil measurements.

Internal consistency, reflecting the degree to which all items within the scale measure the same construct, was assessed by Cronbach’s alpha, yielding a commendable value of 0.858. This result implies that the scale’s components work together cohesively, providing a unified assessment of prolonged pain rather than disparate, unrelated parameters. Internal consistency is crucial to guarantee that the tool does not confuse different symptoms or behaviors unrelated to pain.

The implications of this study extend far beyond the Brazilian healthcare system. Neonatal pain is a global concern given its short-term distress and potential long-term developmental impacts. The introduction of a validated, reliable scale like COMFORTneo-Brazil provides an important template for other regions to adapt culturally and linguistically appropriate instruments, enhancing neonatal care worldwide.

Moreover, the study underscores the vital role of rigorous training for healthcare providers using pain assessment tools. The two raters in this study were thoroughly trained, which is a significant factor influencing reliability outcomes. This finding suggests that successful implementation of COMFORTneo-Brazil will require investment in professional education to standardize pain assessment practices across diverse clinical environments.

The authors emphasize that the COMFORTneo-Brazil scale addresses prolonged pain rather than acute pain episodes, a distinction crucial for clinical decision-making. Prolonged pain often arises from ongoing conditions or interventions and requires sustained management strategies. Prior tools focused primarily on acute pain signals, leaving a gap in assessing the continuous suffering many neonates endure in NICUs.

In parallel with the statistical findings, this study’s design involving both bedside and video assessment methods reflects an innovative approach to pain evaluation. Video recordings allow raters to revisit and carefully analyze behavioral indicators without the immediate pressure of bedside decision-making, offering a valuable complement to real-time assessments.

The integration of such validated pain assessment tools interfaces with broader efforts in neonatology to implement evidence-based practices that improve patient outcomes. Adequate pain management has been linked to better physiological stability, reduced risk of neurodevelopmental impairments, and enhanced parent-infant bonding. Therefore, a tool that accurately detects prolonged pain directly supports these critical health objectives.

In conclusion, the validation and reliability study of the COMFORTneo-Brazil scale marks a pivotal advancement in neonatal pain assessment. Its high correlation with the EDIN scale, excellent intra- and inter-rater reliability, and strong internal consistency collectively establish it as a trustworthy, effective instrument for prolonged pain evaluations in neonates. This work not only enriches the scientific literature but also offers tangible tools for clinicians striving to alleviate pain in one of the most vulnerable patient populations.

With the potential for widespread adoption, the COMFORTneo-Brazil scale represents a significant step forward in neonatal care innovation. As hospitals and NICUs worldwide grapple with the complexities of pain assessment in newborns, validated tools such as this one are indispensable in ensuring precise diagnostics and compassionate treatment. These advancements ultimately contribute to a paradigm shift toward more humane, accurate, and effective neonatal healthcare.

Looking ahead, further research may explore the application of the COMFORTneo-Brazil in various clinical settings, including the adaptation for different languages, cultural contexts, or in preterm populations with varying clinical trajectories. The groundwork laid by this study exemplifies how methodical validation can enhance clinical instruments’ utility and acceptance globally.

Scientists and clinicians alike hail this comprehensive validation as a model for future instrument development, emphasizing the power of statistics combined with rigorous clinical methodology. The COMFORTneo-Brazil scale transcends its role as a measurement tool; it becomes an emblem of commitment to neonatal welfare and scientific precision.

Subject of Research: Validation and reliability assessment of a prolonged pain scale in Brazilian neonates.

Article Title: Validation and reliability of a scale for prolonged pain assessment in Brazilian neonates.

Article References:
Erhardt, A.d.S., Bueno, M., Martins, T.B. et al. Validation and reliability of a scale for prolonged pain assessment in Brazilian neonates. J Perinatol (2025). https://doi.org/10.1038/s41372-025-02430-x

Image Credits: AI Generated

DOI: https://doi.org/10.1038/s41372-025-02430-x