Freshwater Biology

Pacific salmon are keystone species to North Pacific freshwater, coastal, and oceanic ecosystems, but many populations have declined or become more variable in recent decades due to anthropogenic impacts and climate change. Long-term records are needed to understand past changes, identify ecosystem stressors, and guide restoration. We used sedimentary DNA (sedDNA), an emerging paleoecological approach offering broader taxonomic information than traditional methods, to reconstruct ecosystem changes across five Pacific salmon nursery lakes in British Columbia (Canada). DNA metabarcoding targeting the 18S ribosomal RNA gene V7 region was used to track shifts in eukaryotic communities including algae and invertebrates over centuries to millennia. Most lakes showed notable algal community shifts over the past two centuries, with declining green algae and rising diatom relative abundances. Chrysophytes and dinoflagellates also increased over the past century in most lakes, likely driven by stronger thermal stratification, which favored these motile and mixotrophic algae that are capable of vertical migration and flexible nutrient acquisition. We contextualized the trajectories of each core through an ordination analysis based on 98 lakes distributed across British Columbia, which identified land-use changes and longer growing seasons as potential drivers. Network analyses of the sedDNA time series revealed decreasing modularity and increasing connection across lakes, suggesting a shift in resilience mechanisms from between-module buffering by compartmentalized specialists to within-guild insurance via functional overlap among generalists. Our findings demonstrate that sedDNA provides taxonomically rich, long-term insights into aquatic ecological dynamics, which are foundational for understanding and protecting Pacific salmon nursery habitats.

Dams can significantly alter natural riverine systems, but their impact on movement across rivers for most terrestrial vertebrates is poorly known. The completion of Glen Canyon and Flaming Gorge dams in Arizona and Utah (southwestern United States) profoundly changed the Colorado and Green Rivers and have altered habitat for many species. The common side-blotched lizard (Uta stansburiana) offers an excellent opportunity to examine the effects of riverine impoundments on migration and gene flow in terrestrial biodiversity. To assess these effects, we collected tissue samples from 241 Uta stansburiana above and below Glen Canyon Dam and on both sides of the Colorado river at three separate study areas. We used eight microsatellite loci to estimate genetic exchange in the context of genetic diversity and structure. One study area below Flaming Gorge Dam and above Glen Canyon Dam has annual periods of warmer water temperatures and lower flows that are closer to pre-dam conditions, whereas two study areas below Glen Canyon Dam have cold water temperatures year-round, and less pronounced seasonal low flow episodes. We predicted that warmer water temperatures above Glen Canyon Dam would promote greater genetic exchange among populations than below the dam. However, we found evidence for low levels of genetic exchange between sites both above and below Glen Canyon Dam, and a moderate amount of exchange at a site below this dam where lizards could conceivably move from one side to the other. Our results imply that 1) the changes in water temperature and hydrology in dam-altered rivers are a barrier for this species even when the distance from the dam is great; and 2) genetic exchange may be dependent on river morphology. These results are relevant to other small vertebrates, particularly ectotherms, that occupy habitat proximal to a dammed river and has implications for the conservation management of impounded river systems.

Indo-Pacific humpback dolphin (Sousa chinensis) and finless porpoise (Neophocaena phocaenoides) are increasingly threatened across their native range, yet the relative influence of multiple stressors in shaping their population dynamics remains unclear. Current conservation strategies for both species are limited by incomplete data and limited assessment of affecting factors. Here, we integrated eDNA metabarcoding with Joint Species Distribution Modeling (JSDM) to assess how environmental gradients, pollution, and trophic associations interactively influence cetacean distributions in Hong Kong waters. We show that degraded water quality and intensified human activity negatively associated with cetacean occurrence, with clear species-specific responses to different stressors. S. chinensis covaried most strongly with Secchi disc depth, and presence of vessels, while N. phocaenoides was negatively associated with nitrate nitrogen and microbial pollution (sewage). The JSDM variance partitioning analysis highlighted that the occurrence of S. chinensis was primarily associated with anthropogenic disturbances (30.04%), followed by water physical properties (26.63%), whereas N. phocaenoides was more strongly associated with physical (40.9%) and anthropogenic disturbances (35.2%). By integrating eDNA and JSDM, our approach provides fine-scale diagnostics of species-specific vulnerabilities, supporting adaptive conservation strategies and guiding the realignment of protected areas to mitigate biodiversity loss in urbanized marine ecosystems. Environmental ImplicationOur study demonstrates that hazardous water pollutants, including microbial contamination, nutrient enrichment, and chemical stressors, vessel pressure, show strong, species-specific impacts on resident cetaceans in Hong Kong. By integrating eDNA metabarcoding with joint species distribution models, we provide a diagnostic framework that directly links pollutant profiles to ecological risk. These findings highlight that conventional conservation strategies overlooking pollution drivers are insufficient for marine megafauna persistence. Our approach offers an early-warning system for monitoring hazardous pollutants in coastal ecosystems and supports adaptive management strategies to mitigate biodiversity loss in urbanized seascapes.

Zooplankton communities are influenced by multiple environmental factors, including temperature, nutrient and resource availability, which fluctuate seasonally and across years. While long-term average effects can identify overall drivers, they may overlook dynamic, context-dependent effects that govern short-term changes in diversity and abundance. Understanding and disentangling both perspectives is crucial for identifying and estimating the drivers that shape community structure under varying environmental states. Here, we applied Empirical Dynamic Modeling (CCM, SMap) to a 12-year weekly zooplankton time series to identify causal environmental drivers of taxonomic and morphological diversity and quantify how the influence of each driver shifts over time. We contrast these results with static long-term average effects inferred from Generalized Linear Models which included predictor sets identified using covariate adjustment and accounting for temporal autocorrelation. Drivers linked to long-term average associations differed from those regulating short-term zooplankton dynamics, revealing a decoupling between mean environmental effects and the drivers of temporal variability. Temperature emerged as a persistent regulator of zooplankton dynamics across multiple diversity dimensions, while variables commonly associated with background trophic conditions (e.g. particulate organic matter) were primarily associated with long-term patterns and showed limited dynamical relevance. Importantly, we find evidence for morphological homogenisation in response to short-term fluctuations in chlorophyll a, which was not detectable in long-term average relationships. This contrast highlights that mean environmental associations do not necessarily reflect the mechanisms governing community dynamics. Impacts might be underestimated if average effects appear weak, or misinterpreted if arising mainly from shared trends or seasonality rather than direct mechanisms Integrating both perspectives clarifies the identity and role of environmental drivers, improving inference and prediction of zooplankton community change through time.

Microbial communities are critical to the functioning of ecosystems and shape the ecology and evolution of host organisms. However, we have a limited understanding of how host-associated and free-living microbes differ in their structure and biogeography. Here, we test whether host-associated (fish gut) and free-living (lake bacterioplankton) microbes exhibit different metacommunity structure, spatial turnover, and consistency with neutral expectations using two independent lake systems. We characterized microbial communities in lake water (Vancouver Island and Sierra Nevada) and guts in two fish species (stickleback and brook trout) using 16S amplicon sequencing. We compared alpha and beta diversity within lakes, quantified spatial turnover (distance-decay), and tested for departure from neutral abundance-occurrence expectations between bacterioplankton and fish gut microbiomes. Fish microbiomes had lower alpha diversity compared to bacterioplankton, but higher beta diversity within lakes. Bacterioplankton were more similar across lakes yet showed stronger patterns of spatial turnover with distance than fish gut microbiomes. A neutral model explained a substantial proportion of abundance-occurrence relationships in bacterioplankton communities but performed poorly for fish-associated microbes. Our study indicates that host-associated and free-living microbes have disparate patterns of metacommunity structure and spatial turnover consistent with differences in the strength of neutral ecological processes. Fish microbiomes were less diverse at the local scale but more variable across space and time than bacterioplankton communities, suggestive of potentially strong local selection and/or reduced microbial exchange among hosts compared to environmental communities. Importantly, we observed highly consistent patterns across both lake systems despite differences in host species, sampling design, and region, demonstrating that differences in the distribution of host and environmental microbes are potentially widespread. This study demonstrates how host association fundamentally alters the diversity and spatial distribution of microbes, emphasizing the need to incorporate hosts into broader frameworks of microbial biogeography.

Enhanced resilience conferred through sublethal stress pre-exposure may be crucial for reef building corals to cope with variable environments. The effect of stress priming on Acropora cervicornis thermotolerance was evaluated in the context of elevated temperature and ammonium enrichment, 3 and/or 6 M above ambient, respectively. Primed corals were pre-exposed to each stressor individually or in combination for eight days, while non-primed corals remained at ambient conditions. After an eight-day recovery, primed corals and a subset of non-primed corals (naive) were subjected to an acute 15-hour thermal challenge. Coral metabolism, symbiosis, and gene expression were characterized throughout the experiment. Thermal tolerance was quantified as algal symbiont, chlorophyll, and live tissue retention, along with survival probability following acute heating. Primed corals were more likely to retain symbionts and chlorophyll after heat stress and also exhibited slower tissue loss. Moreover, thermal pre-exposure reduced the risk of tissue loss or predicted mortality. Apoptotic regulation differed between primed and naive corals during the initial and secondary heat exposures. Additionally, primed corals exhibited patterns of transcriptional resilience under acute thermal stress. Altogether, results provide support for the capacity of A. cervicornis to gain resilience through pre-exposure to ecologically relevant conditions as well as insights into the molecular mechanisms underpinning this process.

This study investigates the seasonal dynamics of the microbiome within the marine sponge Halichondria panicea from Baltic coastal waters, focusing on its symbiotic relationship with Candidatus Halichondribacter symbioticus. Over 16 months, we observed distinct summer and winter microbial communities, transitioning rapidly between these states during spring and fall. Marine sponges host complex microbiomes composed of diverse microbial taxa that play critical roles in host metabolism and nutrient cycling within marine ecosystems. While our understanding of sponge microbiomes has traditionally been based on static characterizations, the temporal dynamics of these associations across seasonal cycles remain poorly understood. In this study, we investigated temporal variation in bacterial symbionts of Halichondria panicea over 16 months in Baltic coastal waters using high-throughput amplicon sequencing of bacterial 16S rRNA gene sequences. The microbiota of H. panicea exhibited host-specific structure and a high degree of stability across seasons, despite fluctuations in environmental factors such as temperature, salinity, photoperiod intensity, and inorganic nutrient availability. In contrast, bacterial communities in surrounding seawater displayed large seasonal shifts which potentially mix with the sponge bacterial community, suggesting that different degrees of ecological pressures act on free-living and symbiotic marine bacteria. These findings establish an empirical baseline for identifying abnormal shifts in symbiont communities, which could be indicative of environmental stress or biological disturbance events.

Multimodal learning has the potential to improve clinical prediction by integrating complementary data sources, but the incremental value of imaging beyond structured electronic health record (EHR) data remains unclear in real-world settings. We developed a multimodal survival modeling framework integrating optical coherence tomography (OCT) and EHR data to predict time to visual improvement in patients with diabetic macular edema (DME), and evaluated how different ophthalmic foundation model representations contribute to prognostic performance. In a retrospective cohort of 973 patients (1,450 eyes) receiving anti-vascular endothelial growth factor therapy, we compared multimodal models combining 22,227 EHR variables with 196,402 OCT images, with OCT embeddings derived from three ophthalmic foundation models (RETFound, EyeCLIP, and VisionFM). The EHR-only model showed minimal prognostic discrimination (C-index 0.50 [95% CI, 0.45-0.55]). Incorporating OCT improved performance, with the magnitude of improvement depending on the representation. EHR+RETFound achieved the strongest performance (C-index 0.59 [0.54-0.65]), followed by EHR+EyeCLIP (0.57 [0.52-0.62]) and EHR+VisionFM (0.56 [0.51-0.61]). Multimodal models, particularly EHR+RETFound, demonstrated improved risk stratification with clearer separation of Kaplan-Meier curves. Partial information decomposition revealed that prognostic information was dominated by modality-specific contributions, with OCT and EHR providing largely distinct signals and minimal shared information. The magnitude of OCT-specific contribution varied across foundation models and aligned with observed performance differences. These findings indicate that OCT provides complementary prognostic value beyond structured clinical data, but gains are modest and depend strongly on representation choice. Our results highlight both the promise of multimodal modeling for personalized prognosis and the need for rigorous, context-specific evaluation of foundation models in real-world clinical settings.

Abstract Background Spontaneous coronary artery dissection (SCAD) is a well-recognised cause of acute coronary syndrome particularly among women without conventional cardiovascular risk factors. Increasing evidence indicates a genetic contribution; however, the underlying genetic architecture of SCAD remains insufficiently understood. Objective The aim of this study was to assess the prevalence of rare variants in previously reported SCAD associated genes and to explore the potential presence of novel genetic alterations in well-characterised Swedish patients with SCAD. Methods The study comprised 201 patients enrolled in SweSCAD, a national project examining the clinical characteristics, aetiology, and outcomes of SCAD. All individuals had a confirmed diagnosis based on invasive coronary angiography. Comprehensive exome sequencing was performed to identify rare variants contributing to disease susceptibility. Results Genetic variants that have been associated with SCAD according to current clinical genetics practice for variant reporting were identified in approximately 4 % of patients. In addition, rare potentially relevant variants were detected in almost 60 % of patients in genes associated with vascular integrity and vascular remodelling. Conclusion This study supports SCAD as a genetically complex arteriopathy, driven by rare high?impact variants together with broader polygenic susceptibility. Variants in collagen, vascular extracellular matrix, and oestrogen?responsive pathways provide biologically plausible links to female?predominant disease. Although the diagnostic yield of clearly actionable variants is modest, these findings support broader genomic evaluation beyond overt syndromic presentations and highlight the need for larger integrative genomic and functional studies to refine risk stratification and management.

Purpose: To test whether histology-derived gene-expression signatures from routine hematoxylin and eosin slides are prognostic for recurrence and predictive of chemotherapy benefit in early breast cancer. Methods: We conducted a multi-cohort study including CALGB 9344 (anthracycline +/- paclitaxel), CALGB 9741 (standard vs dose-dense chemotherapy), a pooled Chicago real-world cohort, and the American Cancer Society (ACS) Cancer Prevention Studies-II and -3. Whole-slide images were processed with a previously described pipeline to generate 61 histology-derived signatures per patient. The primary endpoint was distant recurrence-free interval (DRFI), except in ACS, where breast cancer-specific survival was used. Secondary endpoints include distant recurrence-free survival (DRFS) and overall survival. The most prognostic signature in CALGB 9344, selected by Harrell's C-index, was evaluated in additional cohorts. Signature-treatment interaction was assessed by likelihood-ratio tests. Multivariable Cox models incorporating age, tumor size, nodal status, estrogen/progesterone receptor status, and signature were fit in CALGB 9344 to improve risk stratification. Results: A total of 7,170 patients were included across four cohorts. The top histology-derived signature in CALGB 9344 showed strong prognostic performance for 5-year DRFI (C-index 0.63) and performed well across validation cohorts (C-index 0.60, 0.70, and 0.62 in CALGB 9741, Chicago, and ACS, respectively). The strongest predictive signal for treatment benefit was observed for DRFS. High-risk cases identified by the signature demonstrated greater benefit from taxane in CALGB 9344 (adjusted hazard ratio [aHR] 0.76 for DRFS, 95% CI 0.66-0.88; interaction p=0.028), from dose-dense chemotherapy in CALGB 9741 (aHR 0.69, 95% CI 0.56-0.85; interaction p=0.039), and differential chemotherapy benefit in the Chicago cohort (aHR 0.84, 95% CI 0.59-1.21; interaction p=0.009). Combined clinical-histology models improved risk stratification and identified low-risk groups with a 2%-10% risk of distant recurrence or breast cancer death. Conclusion: Histology-derived signatures from H&E images are broadly prognostic and, unlike clinical factors, may predict chemotherapy benefit.

Earlier menopause is a risk factor for several age-related diseases, including dementia. The biological pathways linking menopause timing to later-life brain aging are not understood. Leveraging large-scale plasma proteomics in postmenopausal women from the UK Biobank (N=15,012), earlier menopause was associated with upregulation of pro-inflammatory and extracellular matrix degradation pathways, plus accelerated aging across proteomic clocks of organ and cellular aging, including brain and oligodendrocyte aging. Elevated GDF15, a canonical aging marker, was the top protein correlate of earlier menopause. We observed robust replication of menopause timing proteomic shifts in the Women's Health Initiative Long Life Study (N=1,210). In UKB, proteins associated with earlier menopause, including GDF15, exhibited concordant associations with incident dementia risk and brain atrophy, cerebral small vessel disease burden, and white matter microstructural integrity. Collectively, our findings identify proteomic signatures linking ovarian aging to brain aging, providing a framework to inform interventions to reduce dementia risk.

Objectives: To evaluate whether on-site molecular point-of-care testing (POCT) for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) is associated with reduced antibiotic overtreatment for presumed sexually transmitted infections (STIs) among adults living with HIV in rural Uganda. Methods: We conducted a single-site quasi-experimental pre-post intervention study at Kumi Hospital, comparing syndromic management (April-August 2024) with CT/NG POCT-guided management (September 2024-January 2025). Adults living with HIV presenting with symptoms suggestive of an STI were included. Overtreatment in the pre-intervention phase was estimated by comparing antibiotic prescribing with the expected number of CT/NG infections based on positivity observed during the intervention phase. Results: A total of 404 participants were included (203 pre-intervention, 201 intervention). During the intervention phase, CT and/or NG were detected in 14 individuals (7.0%). Median test turnaround time was 95 minutes, enabling same-day treatment in 93% of positive cases. Antibiotic prescribing decreased from 99.0% to 11.4% following POCT implementation (P < 0.001), corresponding to an absolute reduction of 87.6 percentage points. Estimated overtreatment declined from 30.0% to 5.0% for NG and from 74.9% to 6.0% for CT (both P < 0.001). Conclusions: Implementation of CT/NG POCT in routine HIV care was associated with a marked reduction in antibiotic prescribing and estimated overtreatment for presumed STIs. These findings support the potential of POCT-guided, aetiology-based STI management to reduce unnecessary antimicrobial exposure in settings where syndromic management remains standard practice.

Gingival inflammation is associated with dysbiotic oral biofilms characterized by reduced nitrate-reducing capacity and diminished nitric oxide (NO) bioavailability. While dietary nitrate has been shown to influence oral microbial activity, the effects of sustained, localized nitrate delivery on oral biofilm ecology and gingival inflammation remain incompletely defined. In this randomized, double-blind, placebo-controlled trial, 30 adults with gingival bleeding were assigned to receive localized prebiotic nitrate (~0.989 mmol per dose) or placebo for 21 days. The primary outcome was mean bleeding on probing (mBOP). Secondary outcomes included modified Gingival Index (mGI), Quigley-Hein plaque index (QHPI), salivary nitrite (as a proxy for NO bioavailability), oral pH, and microbiome composition assessed by 16S rRNA gene sequencing. Prebiotic nitrate supplementation formulation delivered in a slow-release chewing gum significantly reduced mBOP (25.7% to 15.3%; p = 0.0002) compared to placebo chewing gum. Salivary nitrite levels and oral pH increased, indicating enhanced nitrate metabolism. Microbiome analysis demonstrated enrichment of nitrate-reducing taxa, including Rothia mucilaginosa and Neisseria spp., and a relative reduction in inflammation-associated genera such as Prevotella and Porphyromonas. Localized prebiotic nitrate formula delivered in a functional chewing gum was associated with reduced gingival inflammation and shifts in oral microbiome composition consistent with enhanced nitrate-reducing capacity critical in nitric oxide formation. These findings support a role for biofilm-directed nutritional modulation as a non-antimicrobial approach for managing gingival inflammation and improving nitric oxide bioavailability.

Objectives: In Latin America, up-to-date information to monitor UNAIDS 95-95-95 HIV targets in key populations, such as men who have sex with men, is limited. Elsewhere, structural homophobia restricts access to ART. Conceptual frameworks suggest that intersecting forms of violence and discrimination may negatively influence HIV care outcomes through psychosocial and structural pathways, although empirical evidence remains limited. The study aimed to assess whether sexual orientation outness and recent homophobic violence are associated with not being on ART among Latin American MSM living with HIV. Methods: This cross-sectional study is a secondary analysis of data from LAMIS-2018, including 7,609 MSM aged 18+ with an HIV diagnosis [&ge;]1 year prior from 18 Latin American countries. Participants self-reported ART status, sociodemographic characteristics, homophobic violence, and sexual orientation outness. Bivariate and multivariate logistic regressions identified those factors associated with not being on ART. Results: Nine percent of MSM with HIV were not on ART, 18% reported low sexual orientation outness, and 27% experienced homophobic violence, especially in Andean and Central American countries. Not being on ART was associated with recent homophobic violence (aPR=1.25), low outness (aPR=1.22), unemployment (aPR=1.27), and residence in the Andean subregion (aPR=1.87), Mexico (aPR=1.28), or the Southern Cone (aPR=1.45) versus Brazil. Protective factors included being older (25-39: aPR=0.72; >39: aPR=0.49), living in large cities (aPR=0.72), having a stable partner (aPR=0.78), and university education (aPR=0.74). Conclusions: Recent homophobic violence and low sexual orientation outness were associated with not being on ART among MSM in Latin America. While access varies across countries, structural factors such as stigma and violence may limit engagement in care. Addressing these barriers alongside strengthening health systems may be key to improving ART uptake and advancing progress toward the 95-95-95 targets.

An increasing number of studies highlight the role of saccadic remodulation in compensatory mechanisms following vestibular injury, and the reappearance of SHIMP saccades correlates with symptom improvement measured by the Dizziness Handicap Inventory (DHI). To investigate the influence of attentional processes and working memory on visuo-vestibular interaction, three independent but interrelated experiments were conducted. In the first two experiments, healthy subjects and patients with unilateral or bilateral vestibular deficits underwent vHIT in SHIMP mode and the Functional Head Impulse Test (fHIT), performed first separately and subsequently simultaneously. Mean latency and clustering of SHIMP saccades, together with Landolt C recognition rates, were analyzed. Differences between separate and combined protocols were assessed, and, in patients, correlated with symptom severity measured by the DHI, to determine whether the near-simultaneous execution of tasks mediated by shared parietal cortical substrates influenced performance. In the third experiment, vHIT in HIMP mode and fHIT were performed using separate and combined protocols to evaluate whether recognition-related cognitive load affected recovery saccade latency and clustering. Results suggest that visual recognition modulates visuo-vestibular interaction, supporting integrated dual-task protocols for ecological balance assessment and helping explain clinical discrepancies.

Early detection of breast cancer remains essential for improving clinical outcomes, and complementary non-invasive approaches are needed to support existing screening methods, particularly for women with dense breast tissue. We have previously reported plasma lipid biomarker discovery using untargeted high-resolution liquid chromatography tandem mass spectrometry (LC-MS/MS). In this study, we performed biomarker confirmation and developed machine-learning models applied to targeted plasma lipid measurements for the non-invasive detection of early-stage breast cancer across international cohorts with independent external validation. Targeted LC-MS/MS was used to quantify candidate lipid panels in plasma samples from European discovery cohorts (n = 554) and an independent Australian cohort (n = 266) used for external validation. Data-driven feature selection identified a 15-lipid panel with strong performance in European cohorts (AUC >= 0.94). External validation prior to confidence stratification yielded 76% sensitivity, 64% specificity, and an AUC of 0.81 in the Australian validation cohort. Clinical assay development requires iterative panel and model testing to support translational feasibility and performance in the intended-use population. An analytically viable panel, excluding lipids requiring complex and costly synthesis, achieved comparable accuracy with improved assay robustness. Confidence-based analysis showed enhanced performance for predictions made with moderate to high confidence, with sensitivity up to 89% and AUC up to 0.85, suggesting that ongoing research should focus on strategies to enhance diagnostic model confidence. Importantly, model predictions were independent of breast density, tumour size, grade, subtype, and morphology, indicating biological specificity of the lipid signature. These results demonstrate that calibrated machine-learning models applied to plasma lipid biomarkers can support non-invasive breast cancer detection. Expanding training datasets to include greater diversity will further improve performance in the ongoing development of this lipid-based detection approach.

Background: We aimed to identify data-driven FEV1 trajectory phenotypes post-chronic lung allograft dysfunction (CLAD), relate these phenotypes to patient factors and future graft loss, and develop a classification approach for prospective patients. Methods: We studied adult first lung recipients with probable CLAD from two prospective multicenter cohorts: CTOT-20 (n=206) and LTOG (n=1418). FEV1 trajectories over the first nine months post-CLAD were characterized using joint latent class mixed models, jointly modelling time-to-graft loss to account for informative censoring. Models were fit independently in both cohorts and also only among LTOG bilateral recipients. A classification and regression tree (CART) model was derived in LTOG bilateral recipients and applied to CTOT-20 bilateral recipients. Findings: Four distinct early FEV1 trajectory classes were identified in CTOT-20, with large differences in nine month graft loss (72.3%, 31.1%, 2.2%, 0%). In LTOG, similar trajectory patterns were reproduced, with an additional class demonstrating early post-CLAD FEV1 improvement. Among bilateral recipients, trajectory classes showed a clear risk gradient, including a high-risk class with 100% graft loss and a low-risk class with no early graft loss. A CART model incorporating clinical and spirometric variables demonstrated good discrimination in LTOG bilateral recipients (multiclass AUC 0.85) and consistent class assignment and trajectory patterns when applied to CTOT-20. Interpretation: We identified reproducible, clinically meaningful early post-CLAD FEV1 trajectory phenotypes with differential graft loss risk. These phenotypes and a pragmatic classification tool may support risk stratification, trial enrichment, and improved prognostication for patients and clinicians.

Background: Nigeria bears one of the highest maternal mortality burdens globally, with skilled birth attendance (SBA) remaining critically low in many regions. Understanding the independent determinants of SBA is essential for designing targeted interventions. Methods: This cross sectional study analyzed 21,465 births from the 2018 Nigeria Demographic and Health Survey (NDHS), a nationally representative household survey using stratified two stage cluster sampling. SBA was defined as delivery attended by a doctor, nurse, midwife, or auxiliary midwife. Multivariable logistic regression was used to estimate adjusted odds ratios (aOR) with 95% confidence intervals for the associations between SBA and maternal education, household wealth, place of residence, geopolitical region, maternal age, parity, and antenatal care (ANC) utilization, after accounting for confounding. Results: The overall prevalence of SBA was 44.9%. In the fully adjusted model, higher education (aOR = 7.01, 95% CI: 5.68-8.67), richest wealth quintile (aOR = 6.27, 95% CI: 5.27-7.46), and attending [&ge;]4 ANC visits (aOR = 3.80, 95% CI: 3.51-4.11) were the strongest independent predictors of SBA. Regional inequalities were pronounced, with SBA prevalence ranging from 17.7% in the North West to 85.6% in the South West. Crude effect estimates for education and wealth were substantially attenuated after adjustment, indicating large confounding by correlated socioeconomic factors. Conclusions: Maternal education, household wealth, ANC utilization, and geopolitical region are independent determinants of SBA in Nigeria. Scaling up ANC programs represents the most immediately actionable intervention, while long term gains require investment in girls' education and wealth equity. Targeted strategies for the northern regions are urgently needed. Keywords: skilled birth attendance, maternal mortality, Nigeria, DHS, antenatal care, logistic regression, health equity

Background: Narcolepsy is a debilitating sleep disorder caused by hypocretin deficiency. Aside from its role to induce wakefulness, hypocretin is linked to modulated appetite and metabolism, often resulting in weight gain. Study objectives: We aimed to unravel the comprehensive epidemiological connection between narcolepsy and major cardiometabolic outcomes. Methods: We analyzed cardiovascular and metabolic disease distribution in the FinnGen study. Using longitudinal electronic health records, we assessed associations between narcolepsy, cardiac/metabolic markers, and prescriptions for relevant drugs. Results: Our findings demonstrate significant associations between narcolepsy and metabolic traits (OR [95% CI] = 2.65 [1.81, 3.89]) as well as stroke (OR = 2.36 [1.38, 4.04]). Narcolepsy patients exhibit a less favourable metabolic profile, including higher glucose levels (OR = 1.1143 [1.0599, 1.1715]) and dyslipidaemia. This is supported by increased prescriptions of insulin (OR = 2.269 [1.46, 3.53]), simvastatin (OR = 2.292 [1.59, 3.31]), and metformin (OR = 2.327 [1.66, 3.25]), reflecting high metabolic disturbances. Furthermore, positive associations with antihypertensive and antiplatelet medications were observed, consistent with elevated cardiovascular risk. Conclusion: Taken together, our findings highlight the cardiometabolic burden in narcolepsy. This study enhances understanding of the metabolic and cardiovascular consequences of narcolepsy and offers timely guidance for effective disease control.

Background: Chronic conditions such as hypertension can significantly disrupt daily life and emotional wellbeing. The interaction between patients' perceptions, adherence to antihypertensive medication and quality of life (QoL) remains underexplored outside structured clinical settings. Objectives: To capture unprompted patient perspectives and assess whether hypertension affects QoL and to investigate if patient reported experiences are associated with self-reported antihypertensive medication adherence. Methods: Social media listening (SML) study analyzing 86,368 anonymized posts from individuals with hypertension in 12 countries, collected between January 2022 and May 2024. Posts from 11 countries (n=81,368) were analyzed using artificial intelligence-enabled natural language processing. Posts from China (n=5,000) were analyzed separately using a harmonized framework. Quantitative and qualitative methods assessed variations by country, age, and gender, and associations between emotional expression and antihypertensive medication adherence. Results: Across the 11-country core sample, 45% of posts mentioned at least one QoL impact, most commonly worry/anxiety (11%). Impacts varied across countries. Among 8,096 posts with age identified, individuals <40 years reported emotional balance impacts in 28% of posts versus 22% among those aged 40+. Work/Education impacts were mentioned in 17% of posts by those <40 years vs 12% in 40+. Among 7968 posts explicitly referencing adherence, expressed worry was associated with stricter adherence (62% association score), as were structured routines (79% score), home monitoring (77%), dietary changes (77%), and exercise (71%). In contrast, sadness/depression was associated with inconsistent adherence (71%), as were forgetfulness (79%), side effects (73%), and cost/insurance concerns (65%). Conclusions: These results emphasize the importance of the psychological and emotional impact of hypertension, including on adherence to medication regimens, reinforcing the value of a holistic approach to patient care.