As natural aromatic macrocyclic compounds with an 18-π electron system, porphyrins exhibit key values in multiple fields such as biosensing, imaging, photothermal/photodynamic therapy due to their unique photophysical properties and chemical tunability. Their integration with low toxicity carbon dots (CDs) with tunable optical and physicochemical properties has opened diverse innovative pathways for interdisciplinary nanotechnology research. This review presents a critical analysis of porphyrin-based CDs (p-CDs), highlighting their structural versatility and transformative applications in nanomedicine. By integrating porphyrin’s photophysical prowess with CDs’ biocompatibility, these hybrid materials enable breakthroughs in near-infrared bioimaging, enzymatic-optical dual sensing, and synergistic phototherapies. Synthetic strategies, including covalent π-conjugation, natural precursor carbonization, and metal-nanozyme engineering, are discussed to underscore their structure-activity relationships. In the landscape of biomedicine, p-CDs have emerged as a revolutionary tool, facilitating early disease detection, precise molecular diagnosis, and targeted therapeutic interventions, thereby reshaping the paradigms of clinical practice and patient care. However, challenges remain in large-scale production and biocompatibility assessment. Future research should prioritize biomimetic design and multimodal integration to realize the full potential of p-CDs in precision medicine.

Objective: To determine whether flurbiprofen-containing patient-controlled intravenous analgesia (PCIA) was associated with an increased risk of postoperative nausea and vomiting (PONV) following gynecological laparoscopic surgery. Design: Retrospective single-center case-control study. Setting: Tertiary care hospital in Guangzhou, China. Population: 2430 patients who underwent gynecological laparoscopic surgery from April 1, 2021 to May 11, 2022. Methods: Perioperative data were extracted from electronic medical records. Multivariable logistic regression was used to identify independent risk factors for PONV, supported by propensity score matching (PSM) and subgroup analyses. A directed acyclic graph (DAG) was constructed to guide confounder selection. Main outcome measures: The incidence of PONV within 48 hours after surgery. Results: PONV occurred in 27.7% (554/2000) of patients receiving flurbiprofen-containing PCIA, compared to 23.0% (99/430) without flurbiprofen (absolute risk difference: 4.7%; number needed to harm [NNH] = 21). In multivariable analysis, flurbiprofen use was independently associated with increased PONV risk (adjusted odds ratio [OR] = 1.414, 95% confidence interval [CI] = 1.042–1.918, p = 0.026). Subgroup analysis suggested this association was stronger in older patients and those receiving hydromorphone-based PCIA. Conclusion: Flurbiprofen-containing PCIA is associated with a modest but clinically significant increase in PONV risk after gynecologic laparoscopic surgery. Although it may reduce opioid consumption and shorten hospital stay, clinicians should consider alternative regimens or enhanced antiemetic prophylaxis in high-risk patients.

The increasing sophistication of cyber threats, particularly those leveraging AI, has necessitated a reevaluation of contemporary security paradigms. Zero Trust Architecture (ZTA), grounded in the principle of “never trust, always verify,” has emerged as a foundational framework for modern enterprise security. ZTA alone is insufficient in dynamic, high-value sectors such as aerospace, where persistent threats exploit behavioural blind spots and architectural gaps. This study investigates how AI-driven observation mechanisms—specifically those involving User and Entity Behaviour Analytics (UEBA), Endpoint Detection and Response (EDR/XDR), and cloud-native telemetry—can enhance ZTA implementations. Using a mixed-method approach, we conduct a structured literature review of AI-ZTA integration and develop two case studies based on publicly documented cybersecurity incidents at Airbus and Boeing. We decompose both reference architectures into control layers and evaluate their AI observability maturity using a scoring rubric based on detection feasibility, containment capability, and response automation. The findings indicate that while ZTA principles are increasingly embedded within aerospace security architectures, substantial variability exists in AI augmentation—particularly in behavioural analytics and memory-level anomaly detection. The study concludes by proposing architecture-level recommendations for improving observability coverage, advancing telemetry correlation, and implementing AI-driven threat detection within ZTA-aligned security operations. These insights contribute to a resilient cybersecurity model in sectors where digital supply chains intersect with legacy systems and emerging AI-enabled threats.

Creativity is known to support self-awareness and emotional expression. This study explored therapists’ perspectives about the influence of art therapy on depression and anxiety. Cognitive behavioral art therapy was used as the theoretical foundation as it integrates talk therapy with creativity to reframe distorted thoughts and reduce emotional distress. Methodology A qualitative descriptive approach was employed with individual interviews and thematic analysis, resulting in five themes. 1) Creative self-expression as healing highlights that arts help regulate emotions, reframe irrational thoughts, and improve interpersonal relationships. 2) Embracing imperfection through creativity helps overcome perfectionism and self-doubt. 3) Universality and flexibility of art therapy make it inclusive, culturally sensitive, and adaptable for different ages and genders. 4) Integration with other modalities enhances communication and emotional processing. 5) Empowering therapeutic settings provide safe and supportive spaces that promote resilience and trauma recovery in both individual and group formats, offering opportunities for connection, collaboration, and healing. Limitations and Future Directions While findings highlight the transformative potential of art therapy, the study’s limitations include its small sample size and the researcher’s biases. Future researchers are encouraged to investigate the impact of specific modalities on marginalized populations and incorporate perspectives of caregivers who also provide art therapy.

Humans and animals possess the ability to continual learn, refine, and transfer knowledge throughout their lives. This lifelong learning process relies on neurocognitive mechanisms that support skill development, memory consolidation, and adaptability. In artificial intelligence, lifelong learning is crucial for models that must process and adapt to ever-changing information. However, AI systems struggle with “catastrophic forgetting”, where newly learned data overwrites prior knowledge, posing a major challenge to adaptive learning. Personal AI assistants, in particular, benefit from continuous learning, enabling them to refine user preferences, absorb new instructions, and retain past interactions. This enhances their ability to provide personalized, context-aware responses, ensuring a seamless and intuitive user experience. This paper proposes the Elastic Weight Consolidation ( EWC) method during the learning process, the network parameters are modified and refined to enhance the retention of recognition capabilities for existing classes while assimilating new ones. The experiment has been organized and the suggested method is evaluated with existing incremental and machine learning techniques, including Bidirectional Long Short-Term Memory(97.9%), Learning without Forgetting(94.3%), Incremental Classifier and Representation Learning (94%), Corticohippocampal circuits-based hybrid neural network(97.5%), Extreme Gradient Boosting (93.2%), and Lite Extreme Gradient Boosting(87.2%) on the dataset which is available on the Kaggel by name “16 personality type ”. Experimental findings indicate that the suggested Elastic Weight Consolidation( EWC) technique is higher than the accuracy of existing prevalent incremental learning and machine learning algorithms which is 98.4%, hence significantly enhancing the scalability and intelligence of the classification model.

Pollination of rare plants may be at risk because such species can rely on specialist pollinators. Rare plants within sagebrush steppe ecosystems are seldom studied, but pollen networks can reveal obscure plant-pollinator interactions. We modeled pollination networks in three communities with rare plants (Artemisia simplex, Trifolium barnebyi and Yermo xanthocephalus). We examined bee pollen loads to assess how the pollen of rare plants was collected and moved by local pollinators. We compared specialization and network strength of rare plants against co-flowering species to measure their role and risk of reduced pollination. We observed that Y. xanthocephalus and A. simplex were pollinated by several bees, and they did not appear to be at risk from loss of pollination. Conversely, T. barneybi was highly specialized; most of its pollen was collected and transported by a specialist bee with potentially higher risks of losing pollination services at some sites. Our pollination networks revealed that each rare plant species interacted uniquely with and offered critical floral rewards to visiting insects. Understanding the pollination ecology of rare plants can assist managers when making informed decisions about the conservation and management of rare plant-pollinator mutualisms and sagebrush steppe ecosystems.

The dichotomy of stable equilibrium versus indeterminate competition is a core principle of ecological theory, as is the effect of a predator in the competitive dynamics. Using a model of invasive ant species that act as pest control agents in Puerto Rican coffee farms we explore the intricate interplay between competition, predation, and species coexistence within ecological systems. Employing concepts from complexity science, including period-doubling bifurcations and chaotic transients, this research examines the dynamics between two invasive ant species, Solenopsis invicta, and Wasmannia auropunctata, and the interaction of S. invicta with phorid fly parasitoids. Empirical data from field and laboratory experiments demonstrate that S. invicta typically dominates W. auropunctata unless phorid flies are present, the latter of which alter the S. invicta behavior and reduce its competitive advantage. Extending the Lotka-Volterra framework, we uncover a parameter-dependent chaotic interregnum where neither species maintains consistent dominance, contrary to traditional models of coexistence. This research revisits the well-known conundrum that ecological outcomes are more intricate than merely dominant-subdominant dynamics, suggesting that biodiversity may thrive within this chaotic interregnum, with implications for the management of the pest control system.

Host–parasite interactions are strongly influenced by the dispersal behaviour of both partners, yet direct evidence of parasite-driven active suppression of host dispersal has been lacking. Here, we provide evidence that the parasitic nematode Sphaerularia bombi manipulates its hosts, bumble bee queens (Bombus spp.), to limit their dispersal. We conducted genetic analyses of S. bombi and its hosts in Japan and the Netherlands, and found pronounced genetic differentiation among local S. bombi populations, despite minimal structure among host populations, indicating that infected queens exhibit severely restricted movement. Mark–recapture experiments further confirmed that infected queens tend to remain near their hibernation sites. We also identified cryptic species within S. bombi, based on concordance between mitochondrial haplotypes and nuclear clades, suggesting weak host specificity. Our findings provide the first empirical demonstration that a parasite can actively constrain host dispersal—a strategy likely enhancing mating opportunities and local transmission at the cost of broader range expansion. Parasite populations are probably established through rare, accidental transport of infected hosts, leading to strong founder effects and rapid cryptic speciation. This work highlights a novel mechanism by which parasites can shape host movement ecology and drive their own evolutionary trajectories.

Accurate functional trait data are critical for assessing ecosystem services and processes in fragmented landscapes. We evaluated whether the global EltonTraits 1.0 database adequately represents the functional structure of mammal communities in forest fragments and restoration sites in a highly fragmented Atlantic Forest landscape. We compared the local data on the frequency of occurrence of 30 mammal species (recorded via camera traps) and their locally compiled trait values (from 118 studies) with those from the global trait database. We focused on three key traits (diet, foraging stratum, and activity cycle), and tested the associations between local and global trait sets using species-level functional uniqueness (¯K_i), community-weighted means (CWM), functional diversity (Rao’s Q), and community-level functional uniqueness (U). Compared to global trait datasets, we found: (i) 85% of species in fragments and 77% in restoration forests showed higher ¯K_i with local traits; (ii) CWM values differed significantly between local and global datasets, particularly for crepuscular activity, scansorial/ground-aquatic foraging, and several dietary components, with local data capturing a broader range of ecological strategies across habitats; (iii) global data underestimated Rao’s Q and U in both habitats, suggesting trait convergence in global datasets masking local-scale variation. These gaps arise because the EltonTraits 1.0 database likely aggregates many trait values from pristine ecosystems, inflating niche space, while local communities face multiple effects of environmental filtering. Additionally, species with wide geographic distributions may exhibit greater intraspecific trait variation, which is often averaged in global datasets, potentially contributing to mismatches. Our findings indicate that depending on global data can risk underestimating the roles of specialized species in fragmented ecosystems, emphasizing the necessity for conservation strategies adapted to local-scale data in tropical landscapes. Our results also highlight the importance of integrating local trait information into functional ecology metrics to avoid biased assessments of community structure.

Objectives: Control beliefs are well-established predictors of anxiety symptomatology, yet existing models emphasize the protective effects of high perceived control without considering the influence of individual differences in metacognitive appraisals of control—namely, the evaluation of the control one believes to have and the control they desire to have. In the present study, we propose that control discrepancy (i.e., the subjective appraisal of the misalignment between perceived and desired control) is a distinct metacognitive vulnerability factor for generalized anxiety disorder (GAD). Methods: In a large non-clinical sample (N = 1,325; M age = 35.9, SD = 16.0), we examined whether control discrepancy predicted elevated GAD risk and greater GAD symptom severity beyond traditional control constructs. Participants completed validated measures assessing mental health symptoms and control beliefs. Results: Results from LASSO-regularized logistic and generalized ordered logistic regressions revealed that control discrepancy was a significant predictor of both GAD risk and symptom severity. Notably, perceiving more control than desired presented a particularly elevated risk, even at high levels of perceived control. These associations remained robust after adjusting for depressive symptoms, perceived stress, perceived control, desired control, and their interaction. Conclusion: Findings provide initial evidence of control discrepancy as a distinct control belief that is uniquely associated with GAD symptomatology beyond that of perceived control, desired control, and their interaction. These results call for a re-evaluation of interventions that primarily target increasing perceived control and underscore the clinical potential of tailoring treatment to reduce control discrepancy, particularly when perceived control greatly exceeds desired control.

This paper presents a privacy-preserving scheme for checking passwords against breach databases using obfuscated deterministic Bloom filter indices. The approach addresses critical limitations in existing methods: k-anonymity schemes leak partial hash information that can increase attack success rates by an order of magnitude, while cryptographic protocols like Oblivious PRF (OPRF) impose significant computational overhead. The proposed scheme employs deterministic noise generation to obfuscate Bloom filter queries, preventing servers from inferring passwords while maintaining the efficiency of Bloom filter lookups. Analysis demonstrates that deterministic noise provides superior privacy guarantees compared to random noise, particularly against correlation attacks over multiple queries. Experimental evaluation shows that the scheme achieves sub-millisecond query times with minimal bandwidth overhead (typically under 1KB per query) while providing strong privacy guarantees. The proposed method is particularly suitable for integration into password managers, authentication systems, and enterprise security infrastructure.

Measuring ecosystem gas fluxes is crucial for understanding the dynamics of ecosystem water and energy cycling. A common method for measuring ecosystem gas fluxes (CO2 , CH4 , N2O) and comparing experimental treatments is the use of closed-loop chambers. However, the output data requires extensive processing before analysis, making the workflow prone to biases and limiting comparability across studies. While various methods exist for processing flux data, they lack re-producibility and automation. The Fluxible R package provides a reproducible way to process raw gas concentration data from closed-loop chambers into an analysis-ready dataset of ecosystem gas fluxes. The processing steps include (1) separating the measurements, (2) fitting a linear, quadratic, or exponential model, (3) as-sessing the quality of the fit, (4) plotting the fluxes for visual inspection, and (5) calculating the fluxes. In addition to reproducibility, Fluxible focuses on homo-geneity and automation in data processing, thereby reducing time investment for users while improving comparability across studies.

The rapid development of e-learning platforms has increased demand for adaptive learning models that enhance engagement and personalization. Adaptive e-learning focuses on understanding the individual’s learning styles, abilities, and adjusting accordingly. This paper proposes a modular hybrid adaptive approach for engagement prediction in e-learning systems, integrating ensemble learning paradigms, bagging, boosting, and stacking to enhance model performance and accuracy. The architecture employs Random Forest (RF), and CatBoost (CB), as base learners, leveraging bagging to reduce variance and boosting to minimise bias, respectively. These models are then combined in a novel stacking ensemble framework, where LightGBM acts as the meta-learner, aggregating the outputs of RF and CB to further improve generalization through a diverse learning mechanism. The Open University Learning Analytics dataset, which includes learner performance, contentment, and course interaction behaviors, was used in the study. Experimental results demonstrate that the proposed hybrid adaptive ensemble approach outperforms the individual models. RF achieved 93.8% accuracy, CatBoost 97.25%, and the stacking model 99.8% training accuracy and testing accuracy of 97.86%, with a minimal generalization gap of 2.2%, depicting strong learning capacity with low overfitting and improved generalization. These findings underscore the effectiveness of ensembled stack-based adaptability in advancing personalized e-learning platforms.

Title page:Authors:Gajendra Acharya: Corresponding authorTidalhealth Peninsula Regional, Department of Internal Medicine, Salisbury, Maryland, USAConceptualization, Supervision, Writing-original draft, Writing-review and editing gajenakash123@gmail.comRohit PanditTidalhealth Peninsula Regional, Department of Internal Medicine, Salisbury, Maryland, USAConceptualization, Writing-original draft, Writing-review and editingRpandit419@gmail.comPradeep MasutaTidalhealth Peninsula Regional, Department of Pulmonary and Critical care, Salisbury, Maryland, USAConceptualization, Supervision, Writing-review and editingPardeepmasuta@gmail.comChen-Rong PhangTidalhealth Peninsula Regional, Department of Internal Medicine, Salisbury, Maryland, USAConceptualization, Supervision, Writing-review and editingphangchenrong@gmail.comOlivia DormanTidalhealth Peninsula Regional, Department of Pulmonary and Critical care, Salisbury, Maryland, USAConceptualization, Writing-review and editingOlivia.dorman@gmail.comIvonne HerreraTidalhealth Peninsula Regional, Department of Rheumatology, Salisbury, Maryland, USAConceptualization, Writing-review and editingibuenano@hotmail.comPrabal TiwariKathmandu University Hospital, Department of Internal medicine, Dhulikhel, NepalWriting-review and editingPrabal.tiwari11@gmail.com

A document by Saied Besharaty. Click on the document to view its contents.

The European River Lamprey is an anadromous migratory fish species of high ecological, cultural, and commercial importance. It is experiencing population decline across its range due to overfishing, habitat degradation, and migratory barriers. However, it remains questionable whether fishways mitigate the impact of barriers and contribute meaningfully to population improvement. In this study we provide insights to effectiveness of the first natural-type fishway constructed in Latvia, located on the Rīva River to facilitate European River Lamprey migration. Results showed a partial improvement in larval abundance after the completion of the fishway, with statistically significant increases detected only in the progeny of generations that migrated two or more years post-construction. However, larval abundance remained inconsistent. Prior to the fishway’s installation, some years even exhibited relatively higher abundance. These findings suggest that while the fishway offers limited benefit, overall, it has not made a significant contribution to improving the natural reproduction success of European River Lamprey. Most likely due to suboptimal fishway design for lampreys. This case study highlights the challenges in designing fish passage systems suitable for non-salmonid species like lampreys. It emphasizes the need for species-specific solutions and long-term monitoring to ensure comprehensive evaluation of the spawning success and effective conservation outcomes.

Title page:Authors:Gajendra Acharya: Corresponding authorTidalhealth Peninsula Regional, Department of Internal Medicine, Salisbury, Maryland, USAConceptualization, Supervision, Writing-original draft, Writing-review and editing gajenakash123@gmail.comHafiza BalochTidalhealth Peninsula Regional, Department of Pulmonary and Critical care, Salisbury, Maryland, USAConceptualization, Supervision, Writing-review and editingNoor2000_2004@hotmail.comPradeep MasutaTidalhealth Peninsula Regional, Department of Pulmonary and Critical care, Salisbury, Maryland, USASupervision, Writing-review and editingPardeepmasuta@gmail.comRohit PanditTidalhealth Peninsula Regional, Department of Internal Medicine, Salisbury, Maryland, USAWriting-original draft, Writing-review and editingRpandit419@gmail.comRobert KimelheimTidalhealth Peninsula Regional, Department of Rheumatology, Salisbury, Maryland, USASupervision, Writing-review and editingrobert.kimelheim@tidalhealth.orgPrabal TiwariKathmandu University Hospital, Department of Internal medicine, Dhulikhel, NepalWriting-review and editingPrabal.tiwari11@gmail.com

A document by Fazhen Xu. Click on the document to view its contents.

Medications with anticholinergic and sedative properties, even when used in isolation, can negatively impact the physical performance of older adults. Managing complex pharmacological regimens in potentially multimorbid patients remains a significant challenge. This study aimed to examine the association between medication burden, as measured by the Drug Burden Index (DBI), and both postural balance and recent falls in community-dwelling older adults. Medication use was assessed through a structured questionnaire covering both prescribed and over-the-counter drugs taken chronically. The DBI was then calculated. Postural balance was evaluated using a BIOMEC400 force platform during a one-legged stance, and fall events over the previous six months were recorded. The sample consisted of 179 participants from a university outpatient clinic; 70.8% were female and 60.0% were white. A total of 75 participants (41.9%) had a low or high medication burden. These individuals demonstrated significantly worse balance across all parameters (Kruskal–Wallis test, p < 0.05). Additionally, medication burden was strongly associated with recent falls (Chi-square test for trend = 34.1, p < 0.0001). ROC curve analysis identified a DBI cut-off point of 0.5 as being associated with impaired balance. In conclusion, a DBI above 0.5 appears to increase the risk of balance impairment and falls in older adults. The DBI may therefore be a useful public health tool to identify high-risk individuals and support safer medication use in this population.

The Conchitas River, located in the southeastern Buenos Aires Metropolitan Area, has experienced severe degradation due to two decades of unregulated urbanization, industrial effluents, and deficient wastewater management. This study aims to assess long-term changes in water quality in the middle basin of the river from 2002 to 2023. We integrated data from four historical studies with new fieldwork conducted in 2022–2023, evaluating physicochemical, bacteriological, and biological parameters. Results revealed a consistent downstream decline in water quality, with conductivity rising from 629 to 1765 µS cm -1, dissolved oxygen decreasing from 10.24 to 0.99 mg L -1, and BOD 5 peaking at 123 mg O 2 L -1. Fecal coliforms exceeded legal limits across all sites, and diatom assemblages were dominated by highly tolerant taxa. The Water Quality Index (WQI) declined from 67.7 upstream to 37.3 near the mouth. These trends highlight chronic pollution and urgent need for integrated watershed management and investment in sanitation infrastructure.

Rescue Thrombectomy for Thrombolysis-Failure in High-Risk Pulmonary Embolism: A Case of Mixed Acute-Chronic Thrombotic BurdenApil Upreti1 , Ayushma Acharya2 , Sujan Ghimire1 , Ritika Bhatta3 , Swarup Sharma Rijal21 Maharajgunj Medical Campus , Institute of Medicine, Maharajgunj ,Kathmandu , Nepal2 Tower Health Reading Hospital , Reading , PA 19610 , United States of America3 Nepal Medical College and Teaching Hospital, Jorpati, Kathmandu, NepalCorresponding Author: Sujan Ghimire Email: ghimiresujan848@gmail.comPhone: 9843724541Affiliation: Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University, Kathmandu, NepalPostal Address: Institute of Medicine, Tribhuvan University, Maharajgunj, Kathmandu Nepal.

The vacuolar H +-ATPase (V-H +-ATPase) plays a crucial role in plant salt tolerance by energizing Na + sequestration into vacuoles and maintaining cytoplasmic Na +/K + homeostasis. Lycium barbarum L. ( L. barbarum) is a well-known halophytic plant. However, the mechanism by which he regulates ion balance to withstand salt stress is not very clear. In this study, we investigated the physiological and molecular mechanisms underlying V-H +-ATPase-mediated salt tolerance in L. barbarum. Under salt stress, L. barbarum exhibited dynamic changes in PM-H +-ATPase and V-H +-ATPase activities, with an initial increase followed by a decline under prolonged stress, correlating with altered Na + and K + distribution. Transcriptomic analysis revealed differential expression of V-H +-ATPase subunits, with the E subunit upregulated and others (A, B, C, H, a, c, d, e) downregulated, suggesting a fine-tuned regulatory response to salinity. Weighted gene co-expression network analysis (WGCNA) identified key modules and hub genes associated with K + homeostasis, highlighting their role in salt adaptation. Furthermore, transgenic overexpression of LbVHA-d2 and LbVHA-a3 in Nicotiana benthamiana ( N. benthamiana) enhanced salt tolerance by modulating H +-ATPase activity and improving Na +/K + balance, particularly in roots under prolonged stress. While LbVHA-d2 and LbVHA-a3 did not physically interact using yeast two-hybrid (Y2H), their co-expression influenced stress responses, indicating potential indirect regulatory crosstalk. Subcellular localization confirmed their plasma membrane association, supporting their role in proton gradient-driven ion transport. These findings demonstrate that V-H +-ATPase subunits critically regulate salt tolerance and provide potential genetic targets for improving crop resilience in saline environments.

Cystic fibrosis (CF) is a progressive, life-limiting genetic disorder caused by mutations in the CFTR gene, leading to dysfunctional chloride channels and multisystem involvement. The introduction of CFTR modulators has revolutionized CF management by targeting the underlying protein defect rather than just alleviating symptoms. These therapies such as Ivacaftor, Lumacaftor/Ivacaftor, Tezacaftor/Ivacaftor, and Trikafta have significantly improved outcomes in lung function, nutrition, and quality of life, particularly in patients with specific CFTR mutations. However, most evidence has been derived from adolescent and adult populations, leaving a knowledge gap regarding long-term efficacy and safety in children under 12. This narrative review synthesizes recent evidence, particularly advancements from 2024 to 2025, and compares available modulators with a focus on pediatric populations. It highlights the promising early outcomes of newer therapies like Trikafta and Alyftrek™, while also addressing concerns such as hepatotoxicity, pharmacokinetic variability, access disparities, and limited genotype coverage. Despite promising initial results, the lack of large-scale longitudinal pediatric data remains a significant barrier to fully understanding the enduring benefits and risks of early CFTR modulator therapy. To optimize pediatric CF care, future research must prioritize long-term studies tailored to younger patients, considering growth, organ development, and equitable access to emerging treatments.

Trevor A. Jackson1,2, Miguel Nájera-Rincón3, Sulav Paudel1, Mitchell K. Weston1, Amy Beattie1, Sean D.G. Marshall1.1AgResearch, Lincoln Tuhiraki, New Zealand;2Biocontrol for International Development, Christchurch, New Zealand.3Instituto Nacional de Investigaciones Forestales, Agrícolas y Pecuarias (INIFAP), Michoacán, México.Correspondence; trevor.jackson@agresearch.co.nz