Vegetation structure drives mosquito community composition in UK's largest managed lowland wetland.

PURPOSE: The rising burden of mosquito-borne diseases in Europe extends beyond urban areas, encompassing rural and semi-urban regions near managed and natural wetlands evidenced by recent outbreaks of Usutu and West Nile viruses. While wetland management policies focus on biodiversity and ecosystem services, few studies explore the impact on mosquito vectors. METHODS: Our research addresses this gap, examining juvenile mosquito and aquatic predator communities in 67 ditch sites within a South England coastal marsh subjected to different wetland management tiers. Using joint distribution models, we analyse how mosquito communities respond to abiotic and biotic factors influenced by wetland management. RESULTS: Of the 12 mosquito species identified, Culiseta annulata (Usutu virus vector) and Culex pipiens (Usutu and West Nile virus vector) constitute 47% of 6825 larval mosquitoes. Abundant predators include Coleoptera (water beetles) adults, Corixidae (water boatmen) and Zygoptera (Damselfy) larvae. Models reveal that tier 3 management sites (higher winter water levels, lower agricultural intensity) associated with shade and less floating vegetation are preferred by specific mosquito species. All mosquito species except Anopheles maculipennis s.l., are negatively impacted by potential predators. Culiseta annulata shows positive associations with shaded and turbid water, contrary to preferences of Corixidae predators. CONCLUSIONS: Tier 3 areas managed for biodiversity, characterised by higher seasonal water levels and reduced livestock grazing intensity, provide favourable habitats for key mosquito species that are known vectors of arboviruses, such as Usutu and West Nile. Our findings emphasise the impact of biodiversity-focused wetland management, altering mosquito breeding site vegetation to enhance vector suitability. Further exploration of these trade-offs is crucial for comprehending the broader implications of wetland management.

Investigating light sensitivity in bipolar disorder (HELIOS-BD).

Many people with bipolar disorder have disrupted circadian rhythms. This means that the timing of sleep and wake activities becomes out-of-sync with the standard 24-hour cycle. Circadian rhythms are strongly influenced by light levels and previous research suggests that people with bipolar disorder might have a heightened sensitivity to light, causing more circadian rhythm disruption, increasing the potential for triggering a mood switch into mania or depression. Lithium has been in clinical use for over 70 years and is acknowledged to be the most effective long-term treatment for bipolar disorder. Lithium has many reported actions in the body but the precise mechanism of action in bipolar disorder remains an active area of research. Central to this project is recent evidence that lithium may work by stabilising circadian rhythms of mood, cognition and rest/activity. Our primary hypothesis is that people with bipolar disorder have some pathophysiological change at the level of the retina which makes them hypersensitive to the visual and non-visual effects of light, and therefore more susceptible to circadian rhythm dysfunction. We additionally hypothesise that the mood-stabilising medication lithium is effective in bipolar disorder because it reduces this hypersensitivity, making individuals less vulnerable to light-induced circadian disruption. We will recruit 180 participants into the HELIOS-BD study. Over an 18-month period, we will assess visual and non-visual responses to light, as well as retinal microstructure, in people with bipolar disorder compared to healthy controls. Further, we will assess whether individuals with bipolar disorder who are being treated with lithium have less pronounced light responses and attenuated retinal changes compared to individuals with bipolar disorder not being treated with lithium. This study represents a comprehensive investigation of visual and non-visual light responses in a large bipolar disorder population, with great translational potential for patient stratification and treatment innovation.

Effects of SPI1-mediated transcriptome remodeling on Alzheimer's disease-related phenotypes in mouse models of Aß amyloidosis.

SPI1 was recently reported as a genetic risk factor for Alzheimer's disease (AD) in large-scale genome-wide association studies. However, it is unknown whether SPI1 should be downregulated or increased to have therapeutic benefits. To investigate the effect of modulating SPI1 levels on AD pathogenesis, we performed extensive biochemical, histological, and transcriptomic analyses using both Spi1-knockdown and Spi1-overexpression mouse models. Here, we show that the knockdown of Spi1 expression significantly exacerbates insoluble amyloid-ß (Aß) levels, amyloid plaque deposition, and gliosis. Conversely, overexpression of Spi1 significantly ameliorates these phenotypes and dystrophic neurites. Further mechanistic studies using targeted and single-cell transcriptomics approaches demonstrate that altered Spi1 expression modulates several pathways, such as immune response pathways and complement system. Our data suggest that transcriptional reprogramming by targeting transcription factors, like Spi1, might hold promise as a therapeutic strategy. This approach could potentially expand the current landscape of druggable targets for AD.

Disagreement concerning atopic dermatitis subtypes between an English prospective cohort (ALSPAC) and linked electronic health records.

BACKGROUND: Subtypes of atopic dermatitis (AD) have been derived from the Avon Longitudinal Study of Parents and Children (ALSPAC) based on presence and severity of symptoms reported in questionnaires (Severe-Frequent, Moderate-Frequent, Moderate-Declining, Mild-Intermittent, Unaffected/Rare). Good agreement between ALSPAC and linked electronic health records (EHRs) would increase trust in the clinical validity of these subtypes and allow inferring subtypes from EHRs alone, which would enable their study in large primary care databases. OBJECTIVES: 1. Explore if presence and number of AD records in EHRs agrees with AD symptom and severity reports from ALSPAC; 2. Explore if EHRs agree with ALSPAC-derived AD subtypes; 3. Construct models to classify ALSPAC-derived AD subtype using EHRs. METHODS: We used data from the ALSPAC prospective cohort study from 11 timepoints until age 14 years (1991-2008), linked to local general practice EHRs. We assessed how far ALSPAC questionnaire responses and derived subtypes agreed with AD as established in EHRs using different AD definitions (e.g., diagnosis and/or prescription) and other AD-related records. We classified AD subtypes using EHRs, fitting multinomial logistic regression models tuning hyperparameters and evaluating performance in the testing set (ROC AUC, accuracy, sensitivity, and specificity). RESULTS: 8,828 individuals out of a total 13,898 had both been assigned an AD subtype and had linked EHRs. The number of AD-related codes in EHRs generally increased with severity of AD subtype, however not all with the Severe-Frequent subtypes had AD in EHRs, and many with the Unaffected/Rare subtype did have AD in EHRs. When predicting ALSPAC AD subtype using EHRs, the best tuned model had ROC AUC of 0.65, sensitivity of 0.29 and specificity of 0.83 (both macro averaged); when different sets of predictors were used, individuals with missing EHR coverage excluded, and subtypes combined, sensitivity was not considerably improved. CONCLUSIONS: ALSPAC and EHRs disagreed not just on AD subtypes, but also on whether children had AD or not. Researchers should be aware that individuals considered as having AD in one source may not be considered as having AD in another.

Mechanical Properties of White Matter Tracts in Aging Assessed via Anisotropic MR Elastography.

Magnetic resonance elastography (MRE) is a promising neuroimaging technique to probe tissue microstructure, which has revealed widespread softening with loss of structural integrity in the aging brain. Traditional MRE approaches assume mechanical isotropy. However, white matter is known to be anisotropic from aligned, myelinated axonal bundles, which can lead to uncertainty in mechanical property estimates in these areas when using isotropic MRE. Recent advances in anisotropic MRE now allow for estimation of shear and tensile anisotropy, along with substrate shear modulus, in white matter tracts. The objective of this study was to investigate age-related differences in anisotropic mechanical properties in human brain white matter tracts for the first time. Anisotropic mechanical properties in all tracts were found to be significantly lower in older adults compared to young adults, with average property differences ranging between 0.028-0.107 for shear anisotropy and between 0.139-0.347 for tensile anisotropy. Stiffness perpendicular to the axonal fiber direction was also significantly lower in older age, but only in certain tracts. When compared with fractional anisotropy measures from diffusion tensor imaging, we found that anisotropic MRE measures provided additional, complementary information in describing differences between the white matter integrity of young and older populations. Anisotropic MRE provides a new tool for studying white matter structural integrity in aging and neurodegeneration.

Exogenous Ketone Esters as a Potential Therapeutic for Treatment of Sarcopenic Obesity.

Identifying effective treatment(s) for sarcopenia and sarcopenic obesity are of paramount importance as the global population advances in age and obesity continues to be a worldwide concern. Evidence has shown that a ketogenic diet can be beneficial for preservation of muscle quality and function in older adults, but long-term adherence is low due in part to the high-fat (> 80%), very low carbohydrate (< 5%) composition of the diet. When provided in adequate amounts, exogenous ketone esters can increase circulating ketones to concentrations that exceed those observed during prolonged fasting or starvation without significant alterations in the diet. Ketone esters first emerged in the mid-1990s and their use in pre-clinical and clinical research has escalated within the past 10-15 years. We present findings from a narrative review of the existing literature for a proposed hypothesis on the effects of exogenous ketones as a therapeutic for preservation of skeletal muscle and function within the context of sarcopenic obesity and future directions for exploration. Much of the reviewed literature herein examines the mechanisms of the ketone diester (R, S-1,3-butanediol diacetoacetate) on skeletal muscle mass, muscle protein synthesis, and epigenetic regulation in murine models. Additional studies are needed to further examine the key regulatory factors producing these effects in skeletal muscle, examine convergent and divergent effects among different ketone ester formulations, and establish optimal frequency and dosing regimens to translate these findings into humans.

An epidemiological study of season of birth, mental health, and neuroimaging in the UK Biobank.

Environmental exposures during the perinatal period are known to have a long-term effect on adult physical and mental health. One such influential environmental exposure is the time of year of birth which affects the amount of daylight, nutrients, and viral load that an individual is exposed to within this key developmental period. Here, we investigate associations between season of birth (seasonality), four mental health traits (n = 137,588) and multi-modal neuroimaging measures (n = 33,212) within the UK Biobank. Summer births were associated with probable recurrent Major Depressive Disorder (ß = 0.026, pcorr = 0.028) and greater mean cortical thickness in temporal and occipital lobes (ß = 0.013 to 0.014, pcorr<0.05). Winter births were associated with greater white matter integrity globally, in the association fibers, thalamic radiations, and six individual tracts (ß = -0.013 to -0.022, pcorr<0.05). Results of sensitivity analyses adjusting for birth weight were similar, with an additional association between winter birth and white matter microstructure in the forceps minor and between summer births, greater cingulate thickness and amygdala volume. Further analyses revealed associations between probable depressive phenotypes and a range of neuroimaging measures but a paucity of interactions with seasonality. Our results suggest that seasonality of birth may affect later-life brain structure and play a role in lifetime recurrent Major Depressive Disorder. Due to the small effect sizes observed, and the lack of associations with other mental health traits, further research is required to validate birth season effects in the context of different latitudes, and by co-examining genetic and epigenetic measures to reveal informative biological pathways.

Farmworker Acceptability of Backpack Hydration Systems.

OBJECTIVE: To improve water access while working and contribute to fewer heat-related illnesses (HRI), backpack hydration systems were provided to over 200 farmworkers to use during the 2022 growing season. Acceptability of the water intake intervention was assessed among farmworkers in eastern North Carolina, USA. METHODS: With a pre-established community-university partnership, the acceptability of the intervention was assessed using a cross-sectional survey. The backpack brand selected included a 3-liter water bladder and attached drinking hose. Data analysis included descriptive and correlation statistics. RESULTS: Among 47 male, migrant farmworkers, most (90%) reported the hydration backpack to be acceptable or completely acceptable to workplace fluid intake. Most (53%) reported using the backpack some of the time, compared to 28% who used it often. The participants reported an average of 4.8 (SD 2.2) liters of water intake from the backpack on a typical workday. Most reported the backpack improved the quantity and frequency of their water consumption. CONCLUSION: This study was an important first step in implementation of hydration backpack systems as an HRI-preventative intervention among farmworkers. Future interventional studies could assess the efficacy of the backpacks on health outcomes, including incidence of dehydration and symptoms of HRI.

Seroprevalence of Measles (Rubeola) Antibodies in Childhood Cancer Survivors.

Background: Measles is reemerging as a public health threat, raising important questions about disease vulnerability among childhood cancer survivors. This secondary analysis assessed the seroprevalence of anti-measles immunoglobulin G (IgG) antibodies as a marker of immune status in survivors of childhood cancer and associated demographic/treatment variables. Method: Participants were childhood cancer survivors who were free of active disease, having routine blood studies drawn, and could provide documentation of having received two doses of measles, mumps, and rubella vaccine before their cancer diagnosis. Patient record review documented demographic and treatment variables. Antimeasles (rubeola) IgG antibody seroprevalence was assessed by enzyme immunoassay for vaccine-specific antibodies. Results: Of 270 survivors evaluated, 110 (42%) were female, 196 (75%) were White, and 159 (61%) were leukemia/lymphoma survivors. Of these 262, 110 (42%) had negative measles seroprevalence, suggesting loss of immunity. Conclusion: Measles antibody surveillance and the need for reimmunization for survivors of childhood cancer survivors outside the transplant setting remains controversial. Our analysis indicates that a substantial proportion of survivors lose vaccine-related immunity to measles. Pediatric oncology nurses play important roles in educating cancer survivors regarding their risk of measles infection, evaluating the need for reimmunization, correcting misinformation about vaccine safety and effectiveness, and working to optimize community herd-based immunity.

Use of beta-blockers in patients with ductal carcinoma in situ and risk of invasive breast cancer recurrence: a Swedish retrospective cohort study.

BACKGROUND: Retrospective observational studies suggest a potential role of beta-blockers as a protective strategy against progression and metastasis in invasive breast cancer. In this context, we investigated the impact of beta-blocker exposure on risk for progression to invasive breast cancer after diagnosis of ductal cancer in situ (DCIS). METHODS: The retrospective study population included 2535 women diagnosed with pure DCIS between 2006 and2012 in three healthcare regions in SwedenExposure to beta-blocker was quantified using a time-varying percentage of days with medication available. The absolute risk was quantified using cumulative incidence functions and cox models were applied to quantify the association between beta-blocker exposure and time from DCIS diagnosis to invasive breast cancer, accounting for delayed effects, competing risks and pre-specified confounders. RESULTS: The median follow-up was 8.7 years. One third of the patients in our cohort were exposed to beta-blockers post DCIS diagnosis. During the study period, 48 patients experienced an invasive recurrence, giving a cumulative incidence of invasive breast cancer progression of 1.8% at five years. The cumulative exposure to beta-blocker was associated with a reduced risk in a dose-dependent manner, though the effect was not statistically significant. CONCLUSION: Our observational study is suggestive of a protective effect of beta-blockers against invasive breast cancer after primary DCIS diagnosis. These results provide rationales for experimental and clinical follow-up studies in carefully selected DCIS groups.

Extending the Depth of Focus of an Infrared Microscope Using a Binary Axicon Fabricated on Barium Fluoride.

Axial resolution is one of the most important characteristics of a microscope. In all microscopes, a high axial resolution is desired in order to discriminate information efficiently along the longitudinal direction. However, when studying thick samples that do not contain laterally overlapping information, a low axial resolution is desirable, as information from multiple planes can be recorded simultaneously from a single camera shot instead of plane-by-plane mechanical refocusing. In this study, we increased the focal depth of an infrared microscope non-invasively by introducing a binary axicon fabricated on a barium fluoride substrate close to the sample. Preliminary results of imaging the thick and sparse silk fibers showed an improved focal depth with a slight decrease in lateral resolution and an increase in background noise.

Impact of sustained calorie restriction and weight cycling on body composition in high-fat diet-fed male and female C57BL/6J mice.

OBJECTIVE: The objective of this study was to investigate body composition changes with weight cycling (WC) among adult C57BL/6J mice with diet-induced obesity. METHODS: A total of 555 single-housed mice were fed a high-fat diet ad libitum (AL) from 8 to 43 weeks of age. The 200 heaviest mice of each sex were randomized to the following four groups: ever obese (EO, continued AL feeding); obese weight loser (OWL, calorie-restricted); obese weight loser moderate (OWLM, body weight halfway between EO and OWL); and WC (diet restricted to OWL followed by AL refeeding cycles). Body weight and composition data were collected. Linear regression was used to calculate residuals between predicted and observed fat mass. Linear mixed models were used to compare diet groups. RESULTS: Although weight loss and regain resulted in changes in body weight and composition, fat mass, body weight, and relative body fat were not significantly greater for the WC group compared with the EO group. During long-term calorie restriction, males (but not females) in the OWLM group remained relatively fatter than the EO group. CONCLUSIONS: WC did not increase body weight or relative fat mass for middle-aged, high-fat diet-fed adult mice. However, long-term moderate calorie restriction resulted in lower body weight but greater "relative" fat in male mice.

From little things big things grow: enhancement of an acoustic telemetry network to monitor broad-scale movements of marine species along Australia's east coast.

BACKGROUND: Acoustic telemetry has become a fundamental tool to monitor the movement of aquatic species. Advances in technology, in particular the development of batteries with lives of > 10 years, have increased our ability to track the long-term movement patterns of many species. However, logistics and financial constraints often dictate the locations and deployment duration of acoustic receivers. Consequently, there is often a compromise between optimal array design and affordability. Such constraints can hinder the ability to track marine animals over large spatial and temporal scales. Continental-scale receiver networks have increased the ability to study large-scale movements, but significant gaps in coverage often remain. METHODS: Since 2007, the Integrated Marine Observing System's Animal Tracking Facility (IMOS ATF) has maintained permanent receiver installations on the eastern Australian seaboard. In this study, we present the recent enhancement of the IMOS ATF acoustic tracking infrastructure in Queensland to collect data on large-scale movements of marine species in the northeast extent of the national array. Securing a relatively small initial investment for expanding receiver deployment and tagging activities in Queensland served as a catalyst, bringing together a diverse group of stakeholders (research institutes, universities, government departments, port corporations, industries, Indigenous ranger groups and tourism operators) to create an extensive collaborative network that could sustain the extended receiver coverage into the future. To fill gaps between existing installations and maximise the monitoring footprint, the new initiative has an atypical design, deploying many single receivers spread across 2,100 km of Queensland waters. RESULTS: The approach revealed previously unknown broad-scale movements for some species and highlights that clusters of receivers are not always required to enhance data collection. However, array designs using predominantly single receiver deployments are more vulnerable to data gaps when receivers are lost or fail, and therefore "redundancy" is a critical consideration when designing this type of array. CONCLUSION: Initial results suggest that our array enhancement, if sustained over many years, will uncover a range of previously unknown movements that will assist in addressing ecological, fisheries, and conservation questions for multiple species.

Exploring associations between the Big Five personality traits and cognitive ability with COVID-19 vaccination hesitancy and uptake among mothers and offspring in a UK prospective cohort study.

BACKGROUND: Vaccines reduce the severity of symptoms, and risk of hospitalisation and death from infectious diseases. Yet, vaccination hesitancy persists. Research identifying psychological risk factors for vaccination hesitancy is limited and reports conflicting results. This study sought to address these inconsistencies and explore the role of personality and cognitive ability in COVID-19 vaccination hesitancy and uptake in a prospective cohort study. METHODS: Data came from young adults (Generation-1; G1) and their mothers (Generation-0; G0) in the Avon Longitudinal Study of Parents and Children (ALSPAC). Multinomial logistic regressions, adjusting for several sociodemographic confounders, were used to explore whether personality and cognitive ability were associated with COVID-19 vaccination hesitancy and uptake. 4,960 G1 and 4,853 G0 mothers were included in the study population. FINDINGS: Among G1, 38.4% exhibited vaccination hesitancy, yet 91.9% of the cohort received the vaccine. In adjusted models, higher levels of openness, agreeableness, conscientiousness, and cognitive ability were associated with an increased probability of wanting the vaccine. Similarly, higher levels of agreeableness, openness and cognitive ability were associated with an increased probability of vaccination uptake. However, the evidence of associations with vaccine uptake were generally weaker than with vaccination hesitancy. 56.7% of the offspring who did not want the vaccine either received the vaccine or intended to, whilst 43.3% still had no intention.Among G0 mothers, 25.6% were vaccination hesitant, yet 99.0% of the cohort received the vaccine. 3.1% said they did not want the vaccine; approximately 80% of these either received the vaccine or intended to. We found inconclusive evidence for an association between cognitive ability and vaccination hesitancy among G0 mothers. INTERPRETATION: This study identified psychological factors associated with vaccination hesitancy and uptake. If these associations are causal, these findings may help design more effective vaccination hesitancy interventions.

Hunter-Gatherer children's close-proximity networks: Similarities and differences with cooperative and communal breeding systems.

Among vertebrates, allomothering (non-maternal care) is classified as cooperative breeding (help from sexually mature non-breeders, usually close relatives) or communal breeding (shared care between multiple breeders who are not necessarily related). Humans have been described with both labels, most frequently as cooperative breeders. However, few studies have quantified the relative contributions of allomothers according to whether they are (a) sexually mature and reproductively active and (b) related or unrelated. We constructed close-proximity networks of Agta and BaYaka hunter-gatherers. We used portable remote-sensing devices to quantify the proportion of time children under the age of 4 spent in close proximity to different categories of potential allomother. Both related and unrelated, and reproductively active and inactive, campmates had substantial involvement in children's close-proximity networks. Unrelated campmates, siblings and subadults were the most involved in both populations, whereas the involvement of fathers and grandmothers was the most variable between the two populations. Finally, the involvement of sexually mature, reproductively inactive adults was low. Where possible, we compared our findings with studies of other hunter-gatherer societies, and observed numerous consistent trends. Based on our results we discuss why hunter-gatherer allomothering cannot be fully characterised as cooperative or communal breeding.

Providing Clinical Psychology Training and Trauma-Focused Treatment via Telehealth During COVID-19.

To slow the spread of COVID-19 many mental health providers transitioned to telehealth delivery of trauma-focused treatment for maltreated children. However, these providers faced myriad challenges, including equitable access to equipment and technical demands of telehealth software. Training clinics overseeing pre-doctoral clinical psychology interns experienced the added challenge of providing quality supervision and training via telehealth. This study involves a retrospective application of the Exploration, Preparation, Implementation, and Sustainment (EPIS) framework to describe the innovative adaptation to a telehealth service delivery model in a training clinic providing evidence-based trauma-focused treatment to children and their families. Mixed methods data from clinic records and intern evaluations indicate that compared to pre-COVID (February 2019 - February 2020), during early COVID (April 2020 - April 2021) more patients accessed clinic services, interns reported fewer hours of individual supervision, and interns reported greater satisfaction with their training experiences. Implications for ongoing provision of telehealth services are discussed.

Exploring the causes of COPD misdiagnosis in primary care: A mixed methods study.

BACKGROUND: Within primary care there exists a cohort of patients misdiagnosed with Chronic Obstructive Pulmonary Disease (COPD). Misdiagnosis can have a detrimental impact on healthcare finances and patient health and so understanding the factors leading to misdiagnosis is crucial in order to reduce misdiagnosis in the future. The objective of this study is to understand and explore the perceived causes of COPD misdiagnosis in primary care. METHODS: A sequential mixed methods study, quantifying prevalence and features of patients misdiagnosed with COPD in primary care followed by a qualitative analysis to explore perceived causes of misdiagnosis. Quantitative data was collected for 206 patients identified as misdiagnosed with COPD within the INTEGR COPD study (NCT03482700). Qualitative data collected from 21 healthcare professionals involved in providing COPD care and 8 misdiagnosed patients who were recruited using a maximum variation purposive sampling. RESULTS: Misinterpretation of spirometry results was the prevailing factor leading to patients initially being misdiagnosed with COPD, affecting 59% of misdiagnosed patients in this cohort. Of the 99 patients who were investigated for their underlying diagnosis; 41% had normal spirometry and 40% had asthma. Further investigation through qualitative methodology uncovered reluctance to challenge historical misdiagnoses and challenges in differential diagnosis as the underlying explanations for COPD misdiagnosis in this cohort. CONCLUSIONS: Patients historically diagnosed with COPD without spirometric evidence are at risk of remaining labelled and treated for COPD despite non-obstructive respiratory physiology, leading to a persistent cohort of patients misdiagnosed with COPD in primary care. The lack of spirometry services during and after the COVID19 pandemic in primary care risks adding to the cohort of misdiagnosed patients. Support from respiratory specialists can potentially help to reduce the prevalence of COPD misdiagnosis in primary care. TRIAL REGISTRATION: NCT03482700.

Impact of CFTR Modulation on Pseudomonas aeruginosa Infection in People With Cystic Fibrosis.

BACKGROUND: Pseudomonas aeruginosa is a multidrug-resistant pathogen causing recalcitrant pulmonary infections in people with cystic fibrosis (pwCF). Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have been developed that partially correct the defective chloride channel driving disease. Despite the many clinical benefits, studies in adults have demonstrated that while P. aeruginosa sputum load decreases, chronic infection persists. Here, we investigate how P. aeruginosa in pwCF may change in the altered lung environment after CFTR modulation. METHODS: P. aeruginosa strains (n = 105) were isolated from the sputum of 11 chronically colonized pwCF at baseline and up to 21 months posttreatment with elexacaftor-tezacaftor-ivacaftor or tezacaftor-ivacaftor. Phenotypic characterization and comparative genomics were performed. RESULTS: Clonal lineages of P. aeruginosa persisted after therapy, with no evidence of displacement by alternative strains. We identified commonly mutated genes among patient isolates that may be positively selected for in the CFTR-modulated lung. However, classic chronic P. aeruginosa phenotypes such as mucoid morphology were sustained, and isolates remained just as resistant to clinically relevant antibiotics. CONCLUSIONS: Despite the clinical benefits of CFTR modulators, clonal lineages of P. aeruginosa persist that may prove just as difficult to manage in the future, especially in pwCF with advanced lung disease.