Journal of the Association for Research in Otolaryngology

Musical rhythm is often experienced with a periodic beat, serving as a temporal reference for coordination with the rhythm. Thus far, models of beat processing have mainly relied on representing sensory inputs as patterns of onset timing, with limited consideration of other sensory features. Here, we challenge this view by showing that the internal representation of beat is affected by other temporal features of the stimulus beyond onset timing alone. We recorded electroencephalography (EEG) while participants listened to rhythmic sequences designed to elicit a beat. Across conditions, we manipulated the duration of the tones conveying the rhythms, while keeping all other parameters identical, including overall intensity, speed, and rhythmic pattern structure. Crucially, the beat periodicity was enhanced in neural activity with increased sound duration, even though the beat periodicity was not prominent in the acoustic features, thus ruling out basic sensory confounds. These results demonstrate the preferential role of longer sound durations in fostering temporal scaffolding processes that integrate fast rhythmic inputs into behavior-relevant internal structures such as the beat. More generally, our findings are compatible with a holistic processing account whereby a range of features beyond onset timing may be integrated into a neural representation of rhythm. Graphical Abstract: Fig. 2EEG was recorded while listeners heard rhythmic sequences eliciting a beat. Sound duration (sonic duty cycle) was varied across four conditions while speed, pattern, and intensity stayed constant. Beat-related EEG responses increased with longer sounds, and were enhanced in all conditions compared to auditory nerve model envelopes, which did not show prominent energy at the beat periodicity, ruling out sensory confounds. Results support holistic rhythm processing beyond onset timing alone. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=101 SRC="FIGDIR/small/721298v1_fig2.gif" ALT="Figure 2"> View larger version (27K): org.highwire.dtl.DTLVardef@10a0599org.highwire.dtl.DTLVardef@f5a95forg.highwire.dtl.DTLVardef@42d1ceorg.highwire.dtl.DTLVardef@dc58a7_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 2.C_FLOATNO EEG and auditory nerve model output analysis based on magnitude spectrum and autocorrelation. Each row represents a duty cycle condition. The two columns on the left represent the magnitude spectrum-based analysis. The first column represents the group-level averaged magnitude spectra at a pool of fronto-central electrodes, across conditions. Beat-related frequencies are shown in red, and beat-unrelated frequencies are shown in blue. Scalp topographies of the neural activity measured at the average magnitudes of beat-related (in red circle) and unrelated (in blue circle) frequencies are represented as insets. The second column represents the normalized magnitude spectra obtained from the auditory nerve model output for each duty cycle sequence. The two columns on the right represent the autocorrelation-based analysis (for visualization purposes, only a subset of lags from 0 to 2.4 s corresponding to the pattern duration is shown). The first column represents the group-level averaged autocorrelation function measured from the same pool of fronto-central electrodes, across conditions. Beat-related lags are shown in red, and beat-unrelated lags are shown in blue. The second column represents the autocorrelation function of the auditory nerve model output for each duty cycle sequence. C_FIG

Understanding speech in noisy environments (SPIN) is an important everyday ability, and engaging in musical activities has been proposed as a factor that may support this ability. However, the cognitive mechanisms underlying a potential musical advantage in SPIN perception remain unclear. Here we investigated whether musical sophistication is associated with better SPIN perception in a large population-based sample, and whether this relationship is mediated by auditory working memory (AWM), verbal working memory (VWM), or non-verbal intelligence. We recruited 203 participants and measured SPIN perception at both word and sentence levels. Musical sophistication was assessed using the Goldsmiths Musical Sophistication Index (Gold-MSI). AWM was measured using delayed matching of tone frequency or the modulation rate of amplitude modulated white noise, VWM was based on backward digit span task, and non-verbal intelligence used matrix reasoning. Mediation analyses revealed that AWM fully mediated the relationship between musical sophistication and SPIN perception, whereas VWM showed no mediation effect. Non-verbal intelligence showed a partial mediating effect. Additional control analyses using structural equation modelling revealed that the indirect effect through AWM remained significant after accounting for age, hearing thresholds, and non-verbal intelligence. Together, these findings suggest that individuals with greater musical sophistication demonstrate better daily life listening abilities, and that superior auditory working memory may be the key cognitive mechanism underlying this advantage.

Vestibular neurons are core elements of the pathways involved in vestibulo-motor functions, such as vestibulo-spinal and vestibulo-ocular reflexes. To meet behavioral needs, electrophysiological neuronal properties are adequately adapted to the sensory-motor computation sustaining these distinct vestibular reflexes. During frog metamorphosis, there is a complete reorganization of the posturo-locomotor system while the oculomotor system remains minimally changed, probably associated to so far unknown changes in vestibular neuronal properties. We used this unique model to investigate the central developmental mechanisms underlying such a reconfiguration of vestibular-associated behaviors. Central vestibular neurons exhibit two types of electrophysiological phenotypes: tonic neurons with a continuous discharge and phasic neurons with a transitory discharge mainly due to the activation of Kv1.1 channel. Electrophysiological recordings and Kv1.1 immunolabeling of vestibulospinal (VS) and vestibulo-ocular (VO) neurons at both larval and juvenile stages revealed that the majority of VS neurons exhibited a tonic discharge in larvae but a phasic discharge in juvenile, while VO neurons remained mainly tonic throughout development. Changes in phasic and tonic neurons proportions in VS population are partly explained by neurogenesis. But we provide evidences that an electrophysiological phenotype switch is a concomitant developmental mechanism participating in the maturation of these central vestibular neurons. All together our results showed that the maturation process in central vestibular neuronal groups is highly related to the metamorphosis-induced remodeling of vestibulo-motor functions they are involved in, with the ultimate purpose of ensuring an adequate adaptation of neuronal elements properties to the developmental changes of behavioral constrains.

Purpose: This study estimated out-of-pocket (OOP) expenses associated Human African Trypano-somiasis (HAT) care, in the Democratic Republic of the Congo (DRC) and explored how they influ-enced care-seeking behavior and participation in HAT control, aiming to inform effective and finan-cially accessible elimination strategies. Methods: A sequential mixed-methods study was conducted using 16 semi-structured interviews and 6 focus group discussions, followed by a structured survey of 444 recently tested participants across 6 health zones. Medical and non-medical expenditures were collected by health structure type and screening strategy (active vs. passive). Catastrophic health expenditure (CHE) was defined as OOP costs, excluding food, exceeding 10% or 25% of annual household income. Results: Payments at health facilities, transport costs and long distances delayed care-seeking, par-ticularly in passive screening (PS). Active screening (AS) was associated with minimal OOP, 93% of visits were cost-free, with a median OOP of 0.76 USD among those incurring costs. PS generated higher expenses, only 12% of PS visits were cost-free, with a median OOP of 9.08 USD among those with expenditures. Among confirmed cases, median OOP was lower through active (9.84 USD) than PS (24.23 USD). Nearly 90% of confirmed cases sold assets or borrowed money to cover expenses. CHE was uncommon under average household income(<4%), however 36% of passively detected cases exceeded the 10% threshold under minimum-wage income assumptions. Conclusion: Despite free diagnosis and treatment, accessing HAT care in rural, low-resource foci in the DRC still imposes a substantial financial burden. Reaching elimination targets and ensuring eq-uitable access will require minimizing indirect costs and logistical barriers to screening and diagno-sis. As active screening declines, routine health systems assume greater surveillance responsibilities, reducing indirect costs and logistical these barriers will be critical to sustain coverage and maintain an effective and equitable HAT elimination strategy.

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: Spinal pain, including neck pain and low back pain (LBP), is a common musculoskeletal condition and major contributor to disability worldwide. Evidence comparing disability, fatigue and mental health across acute and chronic stages remains limited, particularly in conflict-affected and low-resource settings. This study assessed these outcomes among patients with acute and chronic neck pain and LBP in the Gaza Strip. Methods: A comparative cross-sectional study was conducted among 410 adults attending outpatient physical therapy at Nasser Medical Complex, Khan Younis, Gaza Strip. Participants included 204 with neck pain and 206 with LBP, classified as acute neck pain (n=101), chronic neck pain (n=103), acute LBP (n=102) and chronic LBP (n=104). Disability, fatigue, psychological distress and sleep disturbance were assessed using the Neck Disability Index (NDI)/Oswestry Disability Index (ODI), Fatigue Severity Scale (FSS), Patient Health Questionnaire-4 (PHQ-4) and PROMIS Sleep Disturbance Short Form 8a. Independent t-tests, adjusted linear regression, correlation analyses, clinical-threshold analyses and binary logistic regression were performed. Results: Chronic neck pain and chronic LBP were associated with significantly higher disability, fatigue and psychological distress than acute pain. Chronic neck pain patients had higher NDI, FSS and PHQ-4 scores than acute neck pain patients; chronic LBP patients had higher ODI, FSS and PHQ-4 scores than acute LBP patients (all p<0.001). Sleep disturbance did not differ significantly between groups. Female participants reported higher psychological distress in both pain groups, with higher fatigue in neck pain and higher disability in LBP. Adjusted analyses confirmed that chronic pain status remained associated with higher disability, fatigue and psychological distress. Fatigue was the most consistent factor independently associated with chronic pain status. Conclusions: Chronic spinal pain was associated with greater disability, fatigue and psychological distress than acute spinal pain, while sleep disturbance was common across groups. These findings support early multidimensional assessment, including screening for fatigue and psychological distress. Longitudinal studies are needed to clarify whether these factors contribute to transition from acute to chronic spinal pain.

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.