Journal of Phycology

Telomere length (TL) is increasingly used in ecology as a biomarker of individual quality and environmental stress, yet research on non-model species with complex life histories remains limited. Because TL varies among tissues and across ages in a species-specific manner, identifying non-lethal tissues that reliably reflect whole-organism telomere dynamics is essential for longitudinal telomere studies in the field. This study aimed to evaluate tissue-specific TL in Japanese eel (Anguilla japonica), an endangered catadromous fish. We first mapped the chromosomal distribution of telomeric sequences using fluorescent in situ hybridization (FISH), the first application of this method in this species. We then tested whether muscle and caudal fin, which can be sampled easily and non-lethally, can serve as suitable proxy tissues for TL measurements in wild individuals. Relative telomere length (RTL) was quantified by qPCR in blood, brain, caudal fin, gonads, heart, liver, and muscle. FISH analysis confirmed telomeric repeats at all chromosomal ends, with only weak interstitial signals on three chromosomal pairs unlikely to affect qPCR-based estimates. A generalized additive mixed model and Wilcoxons signed-rank tests revealed significant inter-tissue differences: RTL was shortest in the brain and muscle and longest in liver, blood and caudal fin. Muscle and caudal fin RTL were significantly correlated with RTL in many other tissues, supporting their use as proxy tissues for longitudinal TL monitoring, including responses to environmental variation. Both total length and age were tested as explanatory variables for RTL, and the model including total length showed a better fit than the age-based model. Non-linear relationships between RTL and total length observed in several tissues suggest physiological shifts associated with growth and sexual differentiation. Overall, these findings advance understanding of telomere dynamics in eels and establish muscle and caudal fin as suitable tissues for repeated, non-lethal TL assessment in ecological and conservation contexts.

Reef manta rays (Mobula alfredi) are threatened by fishing and other anthropogenic threats. Which, when coupled with conservative life history traits, have made this species vulnerable to extinction. Spatiotemporal ecological knowledge, such as site fidelity and visitation patterns to key aggregation sites, are imperative for effective conservation management of M. alfredi. A novel method of environmental sensing, remote underwater photo systems (RUPs), was employed to understand drivers of M. alfredi habitat use and resighting patterns. RUPs were deployed at four cleaning sites around Laamu Atoll, Maldives. Between March 2021 and May 2023, 455,458 photos were analysed. Generalised linear models revealed increases in M. alfredi presence in response to high chlorophyll-a concentrations, low illumination moon states, the Southwest Monsoon, and in the morning, while human presence had no effect. Branchial spot patterns allowed for 81 M. alfredi individuals to be identified, from 629 sightings, representing 51.59% of Laamu Atolls previously identified population (n = 157). Cleaning stations are visited more intensively during periods of increased productivity of the Southwest Monsoon, likely in response to greater foraging opportunities near the study areas. Additionally, moon state, used as a proxy for tidal strength, was associated with increased visitation during new moon periods, suggesting that weaker tidal states may facilitate presence. These data support integrating RUPs with observational surveys to improve inferences about habitat use and our understanding of cleaning sites frequented by M. alfredi. This study aims to inform the implementation of Laamu Atolls first marine protected area management plan.

Background: The determinants of immunoglobulin E (IgE) remain poorly understood in older adults, a population with an increasing burden of chronic diseases. Identifying IgE's determinants may improve its clinical interpretation in the evaluation of allergic and IgE-related conditions. Objective: To investigate age, sex, smoking, alcohol, body mass index (BMI), corticosteroid use, and season as potential determinants of total IgE (tIgE) and inhaled allergen-specific IgE (sIgE). Methods: Using Rotterdam Study data, we investigated the determinants of tIgE and sIgE using multivariable linear regression. Longitudinal changes and the effects of corticosteroids were assessed with linear mixed models. Results: We included 8769 participants, of which 478 had repeated IgE measurements. Age showed a U-shaped relationship with tIgE and L-shaped relationship with sIgE (both p<0.001). Women had lower tIgE (OR [95%CI]: 0.69 [0.65-0.74]), whereas current smokers (1.34 [1.23-1.46]), higher BMI (1.01 [1.01-1.02]), topical corticosteroid users (1.27 [1.07-1.50]) and inhaled corticosteroid users (1.93 [1.64-2.26]) showed higher tIgE. Women (0.96 [0.92-1.00]), former smokers (0.87 [0.83-0.91]) and current smokers (0.72 [0.68-0.76]) had lower sIgE, whereas topical corticosteroid users (1.20 [1.07-1.35]) and inhaled corticosteroid users (1.20 [1.07-1.35]) showed higher sIgE. Over time, tIgE and sIgE decreased (p<0.001) but did not significantly change after corticosteroid use. Conclusion: We identified age, sex, smoking, BMI, season and topical and inhaled corticosteroids as determinants of tIgE and sIgE. Incorporating these determinants may improve IgE's clinical interpretation for the diagnosis and management of allergic and IgE-related conditions. Future research should investigate how these determinants shape IgE's relationship with chronic diseases in aging populations.

Importance: Foot drop impairs mobility for many children globally, causing life-long health issues. Existing treatments are costly, custom-made, and require frequent clinical visits. A new, low-cost, off-the-shelf splint (OrthoPed) could improve access and user experience. Objective: To determine the feasibility of recruiting children (4-17 years) with moderate foot drop and collecting biomechanical, clinical, and patient-reported outcomes to compare OrthoPed with existing treatments. Design: Single-centre cross-sectional feasibility and pilot study informing a future randomised clinical trial. Participants: Twelve children (target=20; mean age=10.6 {+/-} 3.5 years; 2 females) with moderate foot drop and prescribed orthotic support were recruited via physiotherapy. Intervention: The new OrthoPed splint was compared against existing treatments: ankle foot orthoses (AFOs) and Lycra socks. Main outcome measures: Primary outcome: recruitment and retention rates. Secondary outcomes: biomechanical and clinical gait measures, alongside useability and performance questionnaires. Results: Recruitment reached 22% of eligible participants (an "amber" rating for future trials). Despite four dropouts due to treatment burden, all outcome measures were successfully collected. Preliminarily, OrthoPed supported more natural gait mechanics than AFOs and offered better usability and comfort than AFOs and Lycra socks, potentially enhancing adherence. Conclusions: Recruiting children for orthotic trials is feasible, though coordinating gait testing with routine clinical appointments could improve future recruitment. Importantly, low-cost orthotic devices may provide better usability, accessibility and adherence than existing prescribed options.

Objectives To explore the prevalence, spatial aggregation, and demographic correlates of climate change awareness among adults in Nigeria, as well as impacts on humanitarian health preparedness. Design Nationally representative cross-sectional survey with multivariate logistic regression and Global Moran's I and LISA techniques of spatial autocorrelation analyses was applied. Setting All 36 states and the Federal Capital Territory, Nigeria. Participants 1,600 adults drawn from the Afrobarometer Round 9 nationally representative survey. Interventions None. Main Outcome Measures Prevalence, spatial aggregation, and demographic correlates of climate change awareness among adults in Nigeria, and impacts on humanitarian health preparedness. Results Less than one in three Nigerians (30.1%) was aware of climate change, significantly lower than the 65% found in the continent, and education is the most predictive factor, with tertiary-educated Nigerians more than ten times more likely to be aware of climate change than those with no formal education. Most critically, the poor performance in government climate policies is not found in low-awareness states, but in two geographically distinct risk corridors based on a different mechanism and requiring a different policy response. Conclusions The finding shows that the gap in climate awareness is not a communication problem, it is a structural problem - one that requires a national intervention to reduce and close, but that might not be enough because of educational inequality, gender disparity and geographic marginalization. To prepare the country for humanitarian needs, targeted state-level, gender-responsive programming based on Nigeria's Climate Change Act 2021 is required, and effective intervention to make adaptation to the health impacts of climate change happen will need to start with triggering awareness into adaptive health action before climate hazards surpass the country's humanitarian response capacity. Registration Not applicable. Keywords: Climate change awareness; spatial autocorrelation; humanitarian health preparedness; educational inequality; Nigeria

Background: Access to dental care remains a significant challenge for many children in Canada, particularly among low-income and underserved populations. The Interim Canada Dental Benefit (CDB), introduced in October 2022, aimed to reduce financial barriers to oral health care for children under 12 years of age while the Canadian Dental Care Plan (CDCP) was being developed. While emerging evidence has examined program uptake, limited qualitative research has explored parents and caregivers experiences with the Interim CDB. Objective: This study aimed to explore parents and caregivers experiences with the Interim CDB in Manitoba, Canada, including awareness, access, perceived benefits, challenges, and recommendations for program improvement. Methods: A qualitative descriptive study was conducted using semi-structured interviews with 30 parents and caregivers of children under 12 years of age. Participants were recruited primarily through community dental clinics. Interviews were conducted between July 2023 and February 2024, audio-recorded, and transcribed verbatim. Data were analyzed using inductive thematic analysis to identify key themes and subthemes. Results: Seven interconnected themes were identified: (1) limited and uneven awareness of the Interim CDB; (2) inadequate and inequitable communication strategies; (3) barriers to accessing the benefit, including misconceptions about eligibility and complex application processes; (4) dental providers as key facilitators of access; (5) financial relief and improved access to care; (6) gaps in coverage and ongoing financial strain; and (7) participant-driven recommendations for improvement. While the benefit was widely perceived as reducing financial barriers and enabling access to care, challenges related to awareness, communication, and adequacy of coverage limited its overall effectiveness. Participants emphasized the need for improved communication from government, simplified application processes, expanded eligibility, and increased financial support. Conclusion: The Interim CDB represents an important step toward improving access to dental care for children in Canada. However, this study highlights critical implementation gaps related to awareness, accessibility, and coverage. Addressing these challenges will be essential to ensuring the success of the new CDCP and advancing equitable access to oral health care.

INTRODUCTION: Neuroinflammation and immune dysregulation are increasingly recognized as early drivers of Alzheimer's disease (AD) and AD-related dementias (AD/ADRD), often emerging decades before the onset of clinical symptoms. Despite this, there remains a critical need for non-invasive biomarkers that can capture these early processes, particularly in African Americans, a population at elevated risk for AD/ADRD yet underrepresented in neuroimaging research. In this study, we investigated the relationship between systemic plasma inflammatory markers and brain microstructural integrity in cognitively unimpaired older African Americans. METHODS: Forty-one participants (mean age = 68.68 years) underwent MRI scanning and multi-plex plasma-based inflammatory marker quantification. Microstructural changes were quantified using Diffusion Weighted Imaging (DWI) metrics, including mean diffusivity (MD), radial diffusivity (RD), mean kurtosis (MK), and radial kurtosis (RK). Voxel-wise general linear models, and cluster-based models were used to examine associations between plasma-derived inflammatory markers and brain microstructure. RESULTS: Higher TARC levels were associated with widespread increases in MD and RD across both gray and white matter, implicating reduced microstructural integrity and potential myelin disruption. In contrast, kurtosis-based metrics demonstrated more spatially selective and generally weaker associations, with MK and RK showing limited decreases primarily within white matter tracts. Cluster-level analyses confirmed the robustness of diffusivity findings and highlighted consistent effect sizes across multiple regions. DISCUSSION: These findings suggest that elevated TARC is linked to early microstructural alterations detectable with diffusion MRI, with diffusivity metrics demonstrating greater sensitivity to inflammation-related changes than kurtosis measures in this cohort. This work underscores the importance of incorporating inflammatory biomarkers in neuroimaging studies of aging and highlights diffusion MRI as a promising tool for detecting early neurobiological signatures of AD/ADRD risk in African American populations. Keywords: Systemic Inflammation, TARC, Eotaxin-3, Diffusion MRI, African Americans, ADRD, Aging

Familial longevity, quantified using the Longevity Relatives Count (LRC) score indicating the proportion of ancestral long-lived family members, associates with a pronounced 13 years delayed onset of cardiometabolic disease (CMD). Understanding the molecular basis of familial longevity therefore provides critical insights into mechanisms of cardiometabolic resilience. However, the combined metabolomics and proteomics profile associated with the delayed CMD onset observed in such long-lived family members is not understood yet. Hence, we integrated plasma metabolomics and proteomics in 495 participants from the Leiden Longevity Study to identify molecular signatures associated with (a contrast in) the LRC score. Metabolomics profiling captured 429 features, including amino acid derivatives, nucleosides, and lipid mediators, while proteomics quantified 374 proteins related to cardiovascular, metabolic, and inflammatory pathways. Three within-family analysis approaches were examined and overlapping findings were interpreted. We identified ten metabolites and nine proteins that are associated with increased familial longevity, exemplified by a high LRC score. High LRC scoring individuals exhibited lower levels of amino acid derivatives (prolylhydroxyproline, 5-hydroxy-tryptophan, asymmetric dimethylarginine), nucleosides (2-methylguanosine, 7-methylguanosine, pseudouridine), N-acetylneuraminic acid and quinolinic acid, indicating optimized extracellular matrix integrity, vascular function, and reduced neuroinflammatory activity. Lipid mediators, including elevated 6-keto-PGF1a and reduced 9-HOTrE/alpha-linolenic acid ratio, reflected preserved endothelial homeostasis and attenuated inflammatory signaling. At the proteome level, strong ancestral familial longevity is associated with immune regulators (RETN, NPPB, IGSF8), extracellular matrix components (EFEMP1, EPHB4), and adhesion/signaling molecules (LRP11, ICAM3, KIT, ADGRG2), highlighting coordinated regulation of inflammation, tissue remodeling, and regenerative capacity. Multi-omics pathway analyses indicated convergence on amino acid and nucleotide metabolism, lipid signaling, extracellular matrix remodeling, and receptor-mediated communication. Collectively, these multi-omics systemic signatures define a molecular framework of ancestral familial longevity characterized by reduced inflammation, preserved tissue integrity, and enhanced metabolic and regenerative processes. Our findings provide mechanistic insight into the biology of familial longevity and potentially cardiometabolic resilience.

Rheumatic heart disease (RHD) remains a major public health concern across low- and middle-income countries in the Global South. Early detection through community-based screening of asymptomatic individuals has been identified as a critical strategy for reducing the disease burden. Despite this, the absence of accessible, automated population screening tools continues to impede implementation at scale. This study investigates the screening potential of integrating electrocardiography (ECG) and phonocardiography (PCG) for the early detection of RHD in asymptomatic schoolchildren. The dataset was obtained as part of an ambulatory screening initiative conducted across multiple school sites in rural areas of Ethiopia. It comprised ECG and PCG recordings from 611 asymptomatic schoolchildren aged 10 to 20 years. A comprehensive set of time-frequency, visibility graph and non-linear features were extracted from both signal modalities. These features were subsequently evaluated using machine learning models to assess their utility in the automated screening of early RHD. The best model achieved an average 10-folds cross-validation scores on sensitivity, positive-predictive-value and F1-score of 59.6%, 63.6% and 60.8%, respectively for multimodal ECG and PCG signals. Whereas separate evaluation of ECG showed an F1-score of 61.1% and PCG achieved 23.5%. Key features included the T-wave, the area under the QRS complex, and entropy measures derived from beat visibility graphs in the ECG. In addition, visibility graph features from multi-band S1 and S2 heart sound segments, along with MFCC coefficients from the PCG, were also relevant. However, PCG alone performed poorly and did not show improved results over the ECG features. Although auscultation is key clinical diagnosis tool in symptomatic RHD, combined PCG with ECG features does not enhance asymptomatic RHD detection using the ECG modality alone.

Background Vector control is essential to malaria control and elimination. National Malaria Programmes (NMPs) must make complicated decisions about vector control in the face of evolving epidemiology, biological threats like insecticide resistance, a growing vector control toolbox, and an increasingly constrained funding landscape. The WHO recently published a manual on subnational tailoring of malaria strategies, but limited efforts have been made to understand how NMPs prioritize data and factors that impact decision-making in practice. This study explores vector control decision-making processes, enablers, and barriers across 12 African malaria programmes. Methods We conducted semi-structured interviews with 13 NMP managers or designated representatives from 12 African countries. Interviews were conducted virtually via Zoom or in-person, audio-recorded, transcribed, and thematically analyzed using content analysis. Participants described the interventions in use, decision-making factors, stratification approaches, perspectives on new tools, and operational challenges. Results Insecticide-treated bed nets (ITNs) and indoor residual spraying (IRS) are the core interventions in all countries, with limited but growing use of larval source management, mainly larviciding. Vector control tool selection is driven by WHO guidance, resistance profiles and patterns, epidemiological trends, operational feasibility, and donor funding priorities. Sub-national stratification is widely applied; however, limited analytic and modeling capacity hinder consistent application. Gaps in entomological data result in incomplete data availability to guide stratification. New vector control tools were perceived as promising options, albeit constrained by cost, limited evidence, regulatory delays, and community acceptability. Funding emerged as the dominant driver of decisions, shaping intervention choices regardless of country preference. Participants emphasized substantial gaps in vector control protection related to residual transmission, outdoor biting, insecticide resistance, and unprotected populations living in temporary structures or associated with high-risk occupations. Conclusions Vector control decision-making among NMPs is shaped by an interplay of scientific evidence, operational realities, and external funding dynamics. Strengthening entomological surveillance, enhancing SNT analytic and model output interpretation capacity, securing sustainable financing, and improving community engagement are critical to advancing tailored deployment of tools. Decision-support frameworks that reflect the complexities facing NMPs may further enhance evidence-based, context-specific vector control planning.

Patients with Fontan circulation face evolving risk for cardiovascular morbidity and mortality, yet the interplay between cardiac function, vascular properties, and circulating proteins is incompletely defined. We hypothesized that biochemical biomarkers and multimodal cardiovascular profile differ significantly between Fontan patients and controls, and that selected markers may serve as predictors of reduced single ventricle function. We conducted a prospective observational study at a tertiary pediatric heart center including 31 individuals with Fontan circulation and 52 matched controls. Cardiac function was assessed by echocardiography; vascular phenotyping included carotid intima-media thickness, central and peripheral blood pressure, augmentation index corrected for heart rate, carotid-femoral pulse wave velocity, aging index, and reactive hyperemia index. Compared to controls, the Fontan group had increased pulse wave reflection and central systolic pressure as well as decreased echocardiographic markers of systolic and diastolic function, while pulse wave velocity and other vascular parameters were not significantly different between the groups. Levels of 92 circulating cardiovascular biomarkers were quantified in a subset of 25 of the Fontan cohort and 81 controls using a proximity extension assay. Twenty-two biomarkers differed significantly in the Fontan group compared to controls, including FGF23, REN, HAOX1, and IL17D. Levels of several of these biomarkers correlated with patient age. Most importantly, HAOX1 (a peroxisomal oxidase linked to redox metabolism) and FGF23 (a bone-derived hormone regulating phosphate and vitamin D homeostasis) correlated negatively with ejection fraction within the Fontan group. By contrast, BNP was not associated with cardiac function in the Fontan group. None of the biomarkers correlated with central arterial parameters. In summary, central arterial hemodynamics and biomarkers such as FGF23 and HOAX1 may improve monitoring of cardiovascular function in single ventricle patients with Fontan circulation.

Objectives: Self-applied, low-density EEG offers opportunities to examine sleep in the home environment, yet its feasibility during behavioural sleep interventions remains unexplored. This pilot study aimed to evaluate the feasibility and acceptability of a self-applied, low-density EEG device during sleep restriction therapy (SRT) and explore effects on sleep and affect. Methods: Seventeen adults with insomnia and depressive symptoms completed a 2-week baseline and 4 weeks of SRT. The primary outcome was the proportion of expected EEG recordings completed and scoreable. Secondary outcomes included clinical measures, sleep continuity (sleep diary, actigraphy), sleep architecture (low-density EEG for 9 nights), power spectral density, and affect. Data were analysed with linear mixed models. Cohen's d and 95% confidence intervals were reported. Results: Feasibility was demonstrated (92% of expected EEG nights completed). SRT was associated with reductions in insomnia severity, depressive symptoms, negative affect, and increases in positive affect. Robust improvements were observed across treatment in sleep continuity (SOL, WASO, SE) from diary, which were paralleled by actigraphy. EEG revealed reduced TIB, TST, N1, N2, REM sleep, and REM latency during week one. Reductions in EEG-derived TIB and N1 sleep were maintained at night 28. There were no reliable differences for spectral or spindle measures. Conclusions: These findings suggest that self-applied, low-density EEG during SRT is feasible, acceptable, and may capture sleep changes during treatment. They highlight the potential for multi-night monitoring of sleep interventions at home and elucidating mechanisms underlying therapeutic change.

Background. Women living in leishmaniasis-endemic zones are regularly exposed to the sandfly vector in their environments. While case series and laboratory evidence consistently suggest transplacental transmission of Leishmania parasites with deleterious maternal-fetal effects, this issue has received insufficient attention, particularly in areas where the predominant Leishmania species is mainly associated with cutaneous disease (CL). Methodology/Principal Findings. We conducted an exploratory cross-sectional study in a highly endemic zone of Tabasco, Mexico, enrolling 53 women with singleton term deliveries between April 2018 and April 2020. Placental PCR was positive in 18 (34%) participants. Buccal swabs were positive in 11 (21.2%) of 52 newborns. Immunofluorescence confirmed intracellular amastigotes within macrophages near the vascular endothelium of PCR-positive placentas, with no surrounding inflammatory infiltration. Sequencing revealed homology to Leishmania mexicana or L. amazonensis. Birthweight percentile was modestly lower in the PCR-positive group (predicted mean 53.8% vs. 56.5%, p = 0.76), while small for gestational age showed a non-significant trend toward higher prevalence among PCR-positive cases (prevalence ratio = 2.06, 95% CI: 0.32-13.39, p = 0.45). Conclusions/Significance. Subclinical, dynamic transmission of Leishmania parasites typically associated with cutaneous disease was detected in this endemic zone. The presence of L. mexicana in human placentas was confirmed by immunofluorescence and sequencing, without an associated inflammatory response. These findings highlight the potential of CL-associated Leishmania species to reach the placenta and buccal mucosa of newborns, warranting further epidemiological investigation into the consequences of vertical transmission in regions with endemic CL.

Cardiac rehabilitation is critical for secondary prevention, yet long-term adherence remains low. We present CUOREMA, a new personalized mobile health system integrating self-monitoring diaries, wearable data, virtual coaching, and reinforcement learning-enhanced adaptive interventions to support lifestyle change during and after outpatient cardiac rehabilitation. In a six-month two-center feasibility study (N = 53, Switzerland and France), we evaluated usability, engagement patterns, and preliminary health-related outcomes. Attrition was high: only 19\% of participants used the app on more than 100 days, and questionnaire response rates declined from 55\% at baseline to 13\% at six months. Despite these limitations, exploratory data-driven analysis revealed three distinct engagement clusters (dropout, sporadic, and consistent), which were further supported by matching patterns in app component usage, medication diary adoption, and smartwatch wearing time. Engagement clusters were not associated with demographic factors; instead, psychological themes of patients' personal goals suggested that intrinsic motivation characterized sustained users, whereas extrinsic motivation predominated among early dropouts. User experience was rated positively, and validated questionnaire scores showed no deterioration over time. One center demonstrated a statistically significant improvement in 6-minute walking test performance, though the study was not powered to detect clinical outcomes and selective dropout cannot be ruled out. These findings highlight engagement variability as a central challenge in digital cardiac rehabilitation and suggest that tailoring interventions to individual motivational profiles may improve long-term adherence.

Background: The chromosome 1q31 Th2 pathway-associated interval has been linked to asthma, but its phenotype specificity and cross-ancestry architecture remain unclear. Methods: We analyzed African (AFR) and European (EU) ancestry datasets, including 9,965 asthma cases and 37,391 controls of AFR, and 6,074 cases and 116,255 controls of EU ancestry. Imputed dosage-based association analyses were performed for asthma, steroid-dependent asthma (SDA), and non-steroid-dependent asthma, followed by QC-filtered SDA remapping, leave-one-batch-out analysis, cross-ancestry comparison, and functional enrichment. Results: Strong regional association was observed only for SDA. After quality-control (QC) filtering, the SDA signal remained significant in both ancestries, with 2,280 genome-wide significant variants in AFR and 859 in EU. Cross-ancestry comparison identified 3,129 significant variants: 10 shared, 2,270 AFR-specific, and 849 EU-specific. Shared variants showed concordant effects, whereas 237 variants showed nominal heterogeneity. AFR-specific signals included PTPRC variants with larger effects in AFR. Functional enrichment suggested different biological emphases within the same interval: immune and contractile airway-wall biology in AFR, and additional neuroaxonal components in EU. Conclusions: The 1q31 interval is strongly associated with SDA in both AFR and EU populations, and its fine-scale architecture differs by ancestry. These findings highlight population-specific effects within a shared SDA susceptibility interval, with potential implications for population-informed precision medicine in steroid responsiveness and asthma management.

Blood-based biomarkers are increasingly used to investigate brain health, but collecting venous blood is difficult in remote and field settings. Capillary microsampling offers a practical alternative, although the ability to delay processing and its agreement with gold-standard venous blood require validation. We evaluated Tasso+, a minimally invasive upper-arm capillary blood collection system, for measuring neurological and host-response biomarkers in plasma and serum during an exercise-based protocol. Sampling occurred before, immediately after, and approximately 24-to-36 hours after exercise; Tasso+ samples were processed with or without a 72-hour room-temperature delay. Tasso+ samples were compared with matched venous blood, and Capitainer SEP10 dried plasma spots were also evaluated, using Quanterix Simoa and Alamar Biosciences NULISAseq CNS panel. Tasso+ enabled reliable measurement of several key biomarkers, including GFAP and NfL, even after delayed processing. These findings support capillary microsampling for neurological biomarker studies where venepuncture is challenging, including field-based research and participant-led remote sampling.

Breast cancer was the leading cause of cancer-related mortality among women worldwide in 2022. In Kenya, more than a quarter of breast cancer patients have the aggressive Human Epidermal Growth Factor Receptor 2 positive subtype. Trastuzumab is recommended for its treatment, but high costs have limited access. This study evaluated the cost-effectiveness and affordability of trastuzumab-based regimens to inform their adoption and use in Kenya. A cost-utility analysis was conducted from the healthcare payer perspective over a lifetime horizon. Five trastuzumab-based regimens of varying durations (9-week, 6-month, 9-month, 12-month, and 24-month) were compared with chemotherapy alone. Direct medical costs were estimated using a bottom-up micro-ingredient approach. All costs were reported in 2022 USD. A cohort Markov state-transition model with a monthly cycle length was used to estimate the costs and outcomes for an open hypothetical cohort. Scenario, deterministic sensitivity and probabilistic sensitivity analyses were conducted. A budget impact analysis estimated the financial implications of each regimen. The 9-week regimen had the lowest incremental cost-effectiveness ratio (ICER) of USD 3,230 per QALY, while the remaining regimens had ICERs ranging from USD 4,046 to 9,846 per QALY. The findings were most sensitive to the price and quantity utilized per cycle of trastuzumab. A reimbursement cap of KES 40,000 per cycle reduced ICERs by up to 61%. Over five years, the 9-week regimen would account for 1.2% of the projected insurers budget, whereas the current recommended 12-month regimen would consume 2.82%. Although none of the regimens were cost-effective at Kenyas WTP threshold (USD 1054.80), the 9-week regimen may still be considered by policymakers given its greater affordability. Further cost reductions can be achieved through negotiating lower drug prices, improving access to biosimilars, and implementing vial sharing.

Suboptimal rotavirus vaccine effectiveness in low- and middle-income countries (LMICs) highlights the need for next-generation vaccines, such as the neonatal RV3-BB vaccine. However, there is uncertainty in the duration of protection and future price of vaccines in development. We aim to identify the conditions under which switching to RV3-BB is optimal in Malawi and Ghana, where the current immunization programs use 2-dose Rotarix and 3-dose Rotavac schedules, respectively. A full incremental cost-effectiveness analysis was performed using a validated transmission model calibrated to country-specific rotavirus data. Over 2025-2034, introducing RV3-BB resulted in the largest rotavirus-related burden reduction compared with the current country-specific programs. At moderate willingness-to-pay (~0.5 time Gross Domestic Product per capita), RV3-BB was preferred over Rotavac if price per dose was <$1.2 in Malawi and <$2.5 in Ghana, and/or if the average duration of protection exceeded 40 weeks in Malawi. The RV3-BB vaccine is likely to be cost-effective in Malawi and Ghana, as well as other LMICs, based on expected pricing and duration of protection.

Background: Xylazine and medetomidine are veterinary sedatives increasingly detected as adulterants in the U.S. illicit drug supply. In response, several states have scheduled xylazine. Whether these policies are associated with subsequent changes in xylazine and medetomidine detections remains unclear. Methods: We conducted a state-level, semiannual, serial cross-sectional study using National Forensic Laboratory Information System (NFLIS) data from 1999 to 2025. The primary outcomes were xylazine and medetomidine reports per 100,000 NFLIS drug reports. We used staggered difference-in-differences event-study models to estimate changes in report rates after xylazine scheduling. Sensitivity analyses excluded Florida and expanded the treatment definition to include states that criminalized xylazine without formal scheduling. Falsification analyses examined steroid and antidepressant reports as negative-control outcomes. Results: NFLIS recorded 101,987 xylazine reports and 12,085 medetomidine reports. Xylazine scheduling was not associated with a significant change in xylazine report rates (ATT, 2,872.29 per 100,000; 95% CI, -2,024.63 to 7,769.21; p=.250). In contrast, xylazine scheduling was associated with a significant increase in medetomidine report rates (ATT, 1,536.51 per 100,000; 95% CI, 211.14 to 2,861.88; p=.023). Sensitivity analyses produced similar findings. Negative-control outcomes showed no significant changes. Conclusions: State xylazine scheduling was associated with increases in medetomidine reports but no significant change in xylazine reports. These findings suggest that scheduling may be followed by changes in adulterant composition rather than reductions in overall 2-adrenergic agonist involvement. Our study highlights the importance of monitoring the unintended effects of xylazine scheduling and supporting continued investment in public health surveillance, drug checking, and harm reduction services.

AI-assisted clinical care may compound, rather than correct, existing health inequities. We applied Omar and colleagues' validated four-domain emergency-medicine benchmark to OpenEvidence (OE), a literature-grounded clinical LLM used by tens of thousands of US physicians daily, across 100 emergency-department cases and 20 sociodemographic labels. OE was consistent on the codified clinical decisions, triage, workup, and treatment, but diverged sharply on mental-health screening, where it flagged many historically marginalized groups between three and ten times more often than demographically unmarked cases. Cases labeled as unhoused received recommendations in 78 to 87 percent of responses (versus a 9 percent no-identifier-control rate); cases labeled as transgender in 22 to 24 percent; and Black transgender women specifically in 47 percent. A pre- registered audit of 193 free-text rationales localized the differential to the inner layer of the response, in the structure and tone of the rationale rather than the recommendation itself. Literature grounding may redistribute sociodemographic disparity in clinical AI rather than remove it. As clinical LLMs move toward agentic deployment, equity audits should examine how evidence is applied to each patient, not only whether citations are present.