White matter integrity is a sensitive marker of cerebrovascular health and aging. Physical activity may promote white matter health, but previous studies were limited by self-reported activity and small sample sizes. We examined the association between accelerometer-based physical activity and novel indices of white matter integrity while identifying potential mediators. We analyzed cross-sectional baseline data from 4188 participants (58% women, mean age: 55.4 years) of the Rhineland Study, a prospective cohort study in Bonn, Germany. Physical activity measures (independent variables) were derived from activPAL3 micro-accelerometers. Fractional anisotropy, mean diffusivity, free water fraction, orientation dispersion, and neurite density (outcomes) were obtained from 3 T MR images for the whole brain and across 27 white matter tracts. We performed multivariable polynomial regression and mediation analyses for cardiometabolic and inflammatory factors. Higher energy expenditure was related to lower orientation dispersion, with the association leveling off at higher amounts (standardized βlinear = -0.153 [-0.183; -0.122]; βquadratic = 0.034 [0.017; 0.051]; both p < 0.001). Physical activity was linked to lower neurite density in motor tracts (βs between -0.133 and -0.056, all p < 0.001). However, with advancing age, physical activity became more strongly associated with higher neurite density and lower mean diffusivity of supratentorial fibers. Body weight, cardiometabolic, and inflammatory factors partly mediated effects of physical activity on white matter microstructure. Physical activity is related to white matter integrity in a nonlinear, age- and region-specific way. Physical activity's effects are greatest in sedentary and older individuals, likely mediated through its impact on body composition, cardiometabolic health, and systemic inflammation.
Lead-free rare-earth metal halides hold great promise for solid-state white-light LEDs, yet efficient and spectrally tunable white emission remains challenging. Herein, we adopt an in situ alloying strategy with Ag+ ions to design and synthesize a 0D/3D (Cs3LuCl6/Cs2AgLuCl6) rare-earth halide heterostructure doped with Bi3+ ions. The favorable type-I band alignment and built-in electric field drive efficient interfacial charge transfer, thereby significantly boosting radiative recombination. The heterostructure yields dual-peak self-trapped exciton emissions at 440 and 590 nm, with a photoluminescence quantum yield of up to 92.12%. By tuning the Bi3+ doping concentration, the correlated color temperature can be continuously tuned across the white-light region. The corresponding phosphor-converted white LEDs achieve a color rendering index exceeding 90, excellent thermal stability, and 90% luminance retention after 100 h of operation. These findings provide new insights into the design and fabrication of high-performance white light-emitting luminescent materials for solid-state lighting.
Cognitive models propose that reading aloud relies on two routes, a lexical route for familiar word recognition and a sublexical route for graphene-to-phoneme conversion. Selective disruption of these routes results in surface or phonological dyslexia, respectively. Although the dual route model is well supported behaviorally, its white matter substrates remain incompletely characterized. This study examined the anatomical correlates of acquired lexical and sublexical reading impairments in patients with high-grade glioma in the dominant hemisphere. Thirty-seven patients underwent diffusion tensor imaging (DTI) and a comprehensive reading battery. Reading aloud of regular and irregular words, and pseudowords was used to classify patients as having intact reading, surface dyslexia or phonological dyslexia, based on normative criteria. Six language-related white matter tracts were reconstructed individually for each patient using subject-specific tractography. Each tract was then systematically segmented along its longitudinal axis, allowing diffusion parameters to be extracted from anatomically defined subsegments. Lesion-tract overlap measures were computed to quantify focal tract involvement. Fourteen patients exhibited impaired sublexical reading, 12 impaired lexical reading, and 11 intact reading. Deficits in the sublexical route were more frequent among patients with arcuate fasciculus lesion overlap, and sublexical error rates correlated with global tract integrity. Deficits in the lexical route were associated with the posterior temporal segment of the inferior longitudinal fasciculus, where surface dyslexia errors correlated with reduced fractional anisotropy. In contrast, uncinate fasciculus involvement was more frequent among patients with intact reading, indicating it does not contribute critically to either reading route. These findings provide a fine-grained structure-function mapping of the dual route reading model onto white matter pathways.
Intracranial atherosclerotic stenosis (ICAS) and cerebral small vessel disease (CSVD) frequently co-exist and contribute to poor stroke outcomes. Whether distinct pathophysiological mechanisms mediate large-vessel versus small-vessel disease effects on stroke outcomes, and whether these are modifiable by thrombolysis, remains unknown. In this prospective cohort study, acute ischemic stroke patients with ICAS and/or CSVD were enrolled. ICAS was defined as ≥ 50% cerebral arterial stenosis and CSVD by white matter hyperintensity (WMH), microbleeds or lacunes. Baseline data, 2-week early neurological improvement (ENI), and 3-month modified Rankin scale (mRS) were recorded. Plasma lipids, apolipoprotein B100 (apoB100), homocysteine (HCY), etc., were measured. Logistic regression and causal mediation analyses tested independent predictors and mediators of ENI and poor 3-month outcome (mRS ≥ 3). 262 patients were included. Two novel mediating mechanisms were identified: First, thrombolysis improves early neurological recovery partly via apoB100 reduction (33% mediation, β = 0.33, 95% CI 0.01-0.87), revealing a previously unrecognized fibrinolysis-lipoprotein metabolic interaction. Second, small-vessel disease independently predicts poor 3-month outcomes (deep WMH: OR 2.35, p = 0.03) and additionally mediates 20% of HCY's effect (β = 0.20, 95% CI 0.03-0.46), establishing WMH as a dual-mechanism therapeutic target. Notably, apoB100 exhibits context-dependent mediation: it suppresses the true neurological damage of intracranial stenosis (53% mediation, β = 0.17, 95% CI 0.04-0.34) while facilitating thrombolytic benefit-demonstrating conditional biomarker action in acute stroke. We identified that apoB100 is a modifiable factor linking ICAS and thrombolysis to early neurological recovery, while WMH partly mediates the effect of hyperhomocysteinemia on 3-month functional outcomes. Monitoring and targeting apoB100 may improve secondary prevention strategies in the post-statin era for patients with combined large- and small-artery cerebrovascular disease.Trial registrationChiCTR1800018315, 11/09/2018.
BackgroundAnti-amyloid-β (anti-Aβ) therapy slows cognitive decline but paradoxically accelerates whole-brain gray matter atrophy, complicating outcome prediction.ObjectiveTo identify early imaging markers that predict long-term prognoses.MethodsThis longitudinal cohort study prospectively enrolled participants with early Alzheimer's disease, initiating anti-Aβ therapy. We performed automated T1-weighted MRI volumetric analysis of the whole-brain gray matter, hippocampus, and white matter hyperintensities (WMH). Temporal dynamics were characterized using piecewise linear regression, and predictive utility was assessed using multivariate linear regression analyses.ResultsTwenty-two participants (74 ± 11 years; 14 women) were followed for 376 ± 146 days. Significant volume changes occurred in all regions (p < 0.01). No overt amyloid-related edema was detected, and hemorrhagic events were mild to moderate. Piecewise regression revealed an initial WMH surge that decelerated after 60 days (β=-0.19 [95%CI: -0.33, -0.042], p = 0.01), whereas gray matter regions showed linear volume decline. Early subthreshold WMH expansion predicted long-term atrophy independent of baseline covariates (age, sex, amyloid burden, mini-mental state examination score, drug, and hemorrhagic events) in the hippocampus (β=-0.058 [95%CI: -0.092, -0.025], p = 0.003), and whole-brain gray matter (β=-0.033 [95%CI: -0.065, -0.002], p = 0.04). Early whole-brain gray matter atrophy correlated with the WMH surge (β=-0.53 [95%CI: -0.69, -0.38], p < 0.001) and predicted long-term hippocampal atrophy (β=0.098 [95%CI: 0.038, 0.16], p = 0.004).ConclusionsA transient WMH surge within the first 60 days of therapy mirrors the known time course of amyloid-related imaging abnormalities. Along with concurrent early whole-brain volume loss, this surge independently predicts accelerated long-term hippocampal and whole-brain atrophy, highlighting its potential as an early prognostic imaging marker.
Alzheimer disease pathology and cerebral small-vessel disease frequently coexist in older adults, yet how their interaction influences early clinical progression remains poorly understood, particularly in individuals without dementia. We aimed to investigate how plasma Alzheimer disease biomarkers and white matter hyperintensities (WMHs) interact to influence cognitive trajectories and the risk of progression to cognitive impairment and dementia. We studied 463 nondemented participants from the ADNI (Alzheimer's Disease Neuroimaging Initiative). Linear mixed-effects models assessed interactions between plasma biomarkers and WMHs on cognitive trajectories. Cox models examined incident cognitive impairment and dementia. Moderated mediation analyses explored potential biological pathways. Among 463 participants, plasma phosphorylated tau 217 to β-amyloid 42 ratio was the only biomarker that consistently interacted with WMHs across multiple stages of disease progression, including cognitive decline (Mini-Mental State Examination: β=-0.05 [95% CI, -0.06 to -0.03]; executive function: β=-0.02 [95% CI, -0.03 to -0.01]; memory: β=-0.03 [95% CI, -0.04 to -0.02]; language: β=-0.03 [95% CI, -0.04 to -0.02]; visuospatial function: β=-0.02 [95% CI, -0.04 to -0.01]) and increased clinical risk (cognitive impairment: χ2=15.67, P=0.047; dementia: χ2=15.88, P=0.044). These interactive associations were most pronounced in cognitively normal individuals and men. Moderated mediation analyses indicated that plasma glial fibrillary acidic protein partially mediated the interaction between phosphorylated tau 217 to β-amyloid 42 ratio and WMHs for executive function and language performance. These findings indicate that phosphorylated tau 217 to β-amyloid 42 ratio and WMHs jointly contribute to clinical progression in nondemented individuals, with astrocytic activation potentially involved in this process.
Dementia arises from multifactorial neurodegenerative processes, with growing evidence implicating blood-brain barrier dysfunction, neuroinflammation, and vascular injury as contributors to progressive brain tissue damage. Because decline in white matter microstructural integrity is a prominent feature of brain aging, biomarkers that capture this process may improve dementia risk stratification beyond conventional clinical factors. Fractional anisotropy (FA), derived from diffusion tensor imaging, reflects white matter microstructural integrity and may provide a sensitive marker of downstream injury associated with chronic vascular and barrier dysfunction. We conducted a retrospective single-center study of 528 participants, including individuals with dementia (n = 176), age-matched cognitively normal older adults (n = 176), and a young healthy reference cohort (n = 176), all of whom underwent standardized 3-Tesla diffusion MRI. Dementia prediction was evaluated using elastic net-regularized logistic regression with nested tenfold cross-validation, incorporating 16 prespecified clinical and imaging predictors. Corpus callosum FA showed the largest standardized coefficient within the penalized model, exceeding all demographic and clinical variables. The model demonstrated strong discrimination between dementia and age-matched controls (area under the receiver operating characteristic curve [AUC] = 0.970; sensitivity = 90.9%; specificity = 93.2%). FA also declined stepwise from young adults to cognitively normal older adults to participants with dementia, consistent with progressive white matter microstructural injury across the aging-dementia continuum. These findings indicate that corpus callosum FA provides additional predictive value beyond conventional risk factors and support diffusion MRI as a potentially scalable biomarker of age-related white matter microstructural injury with potential utility for dementia risk stratification and biologically informed prevention strategies.
Soldo [1] raises concerns about the reliability of citizen science-derived photographic records for identifying lamnid sharks in the Mediterranean Sea. Using a recently published juvenile white shark from Croatian waters [2] as a representative case, the author reinterprets the specimen as a porbeagle shark (Lamna nasus) rather than a white shark (Carcharodon carcharias), based primarily on selected dental characters. Given the critically endangered status of white sharks in the Mediterranean [3] and the limited number of confirmed observations [4,5], occurrences of the species in this region serve as valuable population data points [6,7] and merit careful examination. Species identifications and reinterpretations should therefore be well-supported, which includes verification of source materials and firsthand communication with citizen scientists, and make use of multiple diagnostic characters whenever possible. Here, we re-examined the specimen using all observable external and dental characters and show that it is consistent with the white shark. We further demonstrate that reliance on single, variably expressed traits-particularly dental characters affected by ontogeny and individual variation-can lead to erroneous identifications, and emphasize that rigorous taxonomic identifications should depend on a holistic, integrative assessment of all available morphological (and if available genetic) evidence.
What psychological mechanisms make the marketing of unhealthy foods to racial and ethnic minority adolescents persuasive? We proposed that social media promoters who share adolescents' racial or ethnic identity are more interesting to look at than incongruent promoters especially to minority adolescents, and that social modeling of these visually interesting promoters increases susceptibility to choosing unhealthy foods. In two experiments (total n=1408), we tested the impact of visual interest in mock Instagram posts that featured promoters who did or did not share the same race/ethnicity as participants and who were depicted as endorsing unhealthy food or non-food products on adolescents' food choices. In Study 1, Black, but not non-Hispanic White, adolescents reported that racially congruent promoters were more visually interesting than incongruent promoters. In Study 2, minority adolescents who identified as Black, Hispanic, or East Asian reported that congruent promoters were more visually interesting than incongruent promoters. Non-Hispanic White adolescents did not report more interest in congruent, White promoters than incongruent promoters. In both studies, increased visual interest predicted an increase in unhealthy snack selections, but only when the posts endorsed unhealthy foods. We also found that visual interest predicted higher engagement with posts, reflected in stronger likelihood of "liking," commenting, or sharing the post. These findings reveal visual interest as a key attentional mechanism linking identity congruence to persuasion, advancing theories of motivated attention and informing strategies to counteract the influence of racially targeted food marketing.
Hispanic men have vasectomies at markedly lower rates than non-Hispanic White men in the USA, even though vasectomy is safer, more effective, and less expensive than female sterilisation. Conceptualising vasectomy beyond a biomedical intervention, the article positions vasectomy as a site of political contestation where masculinity, sexual expertise, fertility accountability, access to care, and memories of sterilisation abuse intersect. The results run counter to traditional explanations based solely on machismo. Instead, factors including low awareness, sexual dysfunction myths, Spanish-language counselling barriers, lack of insurance coverage for male contraception, female-focused family planning, provider bias, and medical mistrust from sterilisation abuse against Latina and Mexican-origin women help explain the Hispanic-White vasectomy disparity. Recent increases in vasectomy requests following the US Supreme Court ruling on Dobbs v. Jackson Women's Health Organisation, which ended federal constitutional protection for abortion and returned its regulation to individual states, suggest that men will access permanent contraception when reproductive circumstances change. However, inequities may continue to limit Hispanic men's access and use unless sexual and reproductive health policy is culturally grounded, gender-balanced, linguistically accessible and responsive to the history of coercive sterilisation in the USA.
This case report describes an 82-year-old man with a right parasagittal motor cortex intracerebral hemorrhage who presented with visuospatial neglect disproportionate to the primary lesion. Quantitative diffusion tensor imaging analysis revealed white matter damage suggestive of underlying cerebral amyloid angiopathy. These findings highlight the importance of considering underlying conditions such as cerebral amyloid angiopathy and premorbid cognitive function when diagnosing visuospatial neglect in elderly stroke patients. Furthermore, assessing the microstructural integrity of non-lesioned white matter tracts may help identify causes of post-stroke cognitive impairment or unexplained symptoms and provide insight into premorbid cognitive function.
Home modifications are an evidence-based fall prevention strategy, though critical barriers often limit their implementation by individuals at risk for falls. This study assessed the impact of community paramedicine-installed grab bars on emergency medical service (EMS) activations among community-dwelling older adults. Data were accrued for grab bar installations delivered by a single community paramedicine program from September 2018 to August 2023. Study inclusion was limited to community-dwelling adults aged ≥ 50 who received grab bars placed within their household and with at least one EMS activation in the 12 months prior to receipt of grab bars. The Wilcoxon Signed-Rank Test compared activations in the 12 months before and after the installation for all-cause activations and fall-related activations. A total of 389 grab bar recipients met inclusion criteria (57% female, 99% white, mean age 81). All-cause EMS activations showed no significant reduction post-installation. Fall-related EMS activations decreased from a mean of 1.52 to 0.83 activations per person (mean difference: 0.68 calls; 95% CI:[0.23, 1.13]), representing a 45% reduction. Grab bar installations provided by community paramedics to community-dwelling older adults with a prior fall resulted in a significant reduction in fall-related EMS activations. This prevention approach demonstrates high potential for community paramedicine to offer an evidence-based intervention targeting at-risk older adults.
Seborrheic dermatitis (SD) is a chronic inflammatory skin condition likely caused by several factors, including overgrowth of the lipophilic yeast Malassezia, increased sebaceous gland activity, and a potential genetic predisposition, whereas Malassezia folliculitis (MF) is a fungal infection of hair follicles. In this case, a 22-year-old male initially presented with erythematous papules on the malar region and was clinically diagnosed with SD. Following partial improvement with topical and oral antifungals, the patient developed new pustular lesions involving the malar and chin regions, raising suspicion of MF. The absence of comedones and cysts helped rule out Acne vulgaris. Potassium hydroxide mount from pustular swabs revealed numerous fungal spores, prompting further investigation. Culture on modified Leeming and Notman agar yielded yeast colonies, which appeared as budding yeast cells under light and fluorescence microscopy with Calcofluor white stain. Molecular identification using PCR for the ITS regions and RFLP analysis confirmed the isolate as Malassezia furfur. This case highlights the clinical progression from SD to MF, underscoring the pathogenic potential of Malassezia and the importance of integrating clinical, microscopic, and culture-based molecular diagnostic approaches for accurate diagnosis and targeted treatment in dermatological mycoses.
This study aimed to develop and validate a distinct, stable, and interpretable predictive model using machine learning techniques to identify individuals at high risk of pneumonia early after admission. The goal was to provide a potential quantitative reference for implementing preventive interventions in clinical practice. A retrospective nested case-control design was adopted. A total of 822 patients with hemorrhagic stroke admitted between January 2019 and October 2024 were enrolled. Feature selection was performed using LASSO regression to eliminate multicollinearity and identify key predictors. Five machine learning algorithms-logistic regression (LRC), gradient boosting classifier (GBC), random forest classifier (RFC), multilayer perceptron classifier (MLPC), and support vector machine classifier (SVC)-were employed to construct predictive models. Hyperparameters were optimized through 10-fold cross-validation and grid search. Model performance was comprehensively evaluated on an independent test set using metrics including area under the curve (AUC), accuracy, sensitivity, precision, and F1-score. Finally, SHAP (SHapley Additive exPlanations) values were applied to interpret the optimal model and elucidate the contribution of each feature to the prediction. LASSO regression selected 14 key predictors from 57 initial variables. Among the five models, the logistic regression model achieved the best performance on the test set. SHAP-based interpretability analysis revealed that the most influential factors for pneumonia risk prediction were, in descending order: left lower limb muscle strength, total cholesterol (TC), right lower limb muscle strength, low-density lipoprotein cholesterol (LDL-C), white blood cell count (WBC), consciousness status, D-dimer, age, systolic blood pressure (SBP), and bleeding location. This study successfully developed a logistic regression-based predictive model for pneumonia risk in patients with hemorrhagic stroke. The model demonstrated favorable discrimination and stability. It provides an objective, quantitative basis for early identification of high-risk patients, stratified management, and precise prevention and control, supporting a shift from reactive to proactive complication management.
Vascular cognitive impairment and dementia (VCID) is a leading modifiable contributor to dementia, accounting for an estimated 27-33% of attributable dementia cases. Neuroimaging is central to detection, phenotyping, and longitudinal monitoring. This neuroradiology-focused review integrates the STRIVE-2 imaging lexicon with the VasCog-2 clinical framework and reviews the advanced MRI techniques most pertinent to VCID, spanning clinically established to emerging research approaches: arterial spin labelling, diffusion tensor imaging including peak width of skeletonised mean diffusivity (PSMD), quantitative susceptibility mapping, vessel architecture imaging, and resting-state functional MRI. Unlike previous reviews, we consolidate operational quantitative thresholds already informing decisions (the Staals total small-vessel-disease score, longitudinal white matter hyperintensity progression linked to dementia risk, microbleed and cortical superficial siderosis (cSS) criteria for anti-amyloid therapy eligibility, and validated PSMD reference ranges) and we critically address gaps between research-grade acquisitions and routine clinical workflows. Automated segmentation and structured reporting are transitioning into deployment, expanding the radiologist's role to combine pattern recognition with quantitative characterisation. We outline current limitations of standardisation, reproducibility, and external validation that remain prerequisites before quantitative VCID imaging achieves formal regulatory biomarker qualification.
Tracking mortality is essential to advance understanding of population health. Further evaluation of long-term stroke mortality trends and subtypes in the United States is needed to guide preventive public health and clinical interventions. This study used the National Vital Statistics System CDC Wide-ranging Online Data for Epidemiologic Research (WONDER) data for adults aged 25 years and older in the United States from 1970 to 2023. Outcomes included absolute number and age-adjusted mortality of total stroke, and its subtypes acute ischemic stroke and intracerebral hemorrhage. Data were analyzed overall and by sex and race. From 1970 to 2023, overall age-adjusted stroke mortality decreased by 82% from 177 to 32 per 100 000. The age-adjusted mortality of acute ischemic stroke decreased by 81% from 135 to 26 per 100 000, and the age-adjusted mortality of intracerebral hemorrhage declined by 86% from 42 to 6 per 100 000. Sex and race trends were similar, though notably age-adjusted mortality of acute ischemic stroke and intracerebral hemorrhage among those identifying as Black remained highest throughout the time period. Joinpoint regression models identified the 1970s and early 2000s as significant periods of mortality decline. Stroke mortality has significantly declined over the last half century, with decreases in both acute ischemic stroke and intracerebral hemorrhage corresponding to public health and clinical advancements, though disparities remain. Continued efforts in prevention and treatment strategies should be made to further this decline, with particular attention to those identifying as non-White race.
Omicron is known for its higher transmissibility and milder respiratory symptoms than those of other SARS-CoV-2 variants. How comorbidities contribute to mortality outcomes in Omicron-related COVID-19 remains unclear. This study compared clinical features and outcomes between Omicron and non-Omicron variants and identified risk factors for in-hospital mortality. This retrospective cohort study was conducted from April 2020 to September 2022. Patients with COVID-19 infection were divided into Omicron and non-Omicron groups. Demographic data, laboratory results, and treatment information were collected and analyzed. Clinical outcomes for different variants were analyzed. The Omicron group had a greater burden of comorbidities but exhibited lower COVID-19 disease severity and fewer complications than did the non-Omicron group. Overall mortality was relatively high in the Omicron group, primarily due to non-COVID-related causes. In multivariate analysis, a Charlson comorbidity index score of ≥3 (odds ratio [OR] = 4.60, 95% confidence interval [CI] = 1.94-10.91, p < 0.001), severe or critical COVID-19 (OR = 1.60, 95% CI = 1.24-2.07, p < 0.001), a high white blood cell count (OR = 1.00, 95% CI = 1.00-1.00, p = 0.021), and a high C-reactive protein level (OR = 1.01, 95% CI = 1.00-1.01, p = 0.003) emerged as positive predictors of COVID-19-related mortality. Severe or critical COVID-19 and a Charlson comorbidity index score of ≥3 were independently associated with high in-hospital mortality. Intensive monitoring and early intervention should be prioritized for high-risk groups to improve clinical outcomes.
Asparagine synthetase deficiency is a rare autosomal recessive neurometabolic disorder characterized by congenital and progressive microcephaly, severe developmental delay, epilepsy, and progressive cerebral atrophy. Therapeutic experience with L-asparagine supplementation remains limited and heterogeneous. We report a preterm female infant born to consanguineous parents who presented with congenital microcephaly and early-onset myoclonic epilepsy. During follow-up, diaphragmatic eventration was identified and contributed to recurrent episodes of respiratory failure. Metabolic screening studies were unremarkable; however, cerebrospinal fluid asparagine concentration was markedly reduced (4.42 μmol/L; reference range 8-34 μmol/L). Brain magnetic resonance imaging demonstrated cerebral atrophy with white matter involvement. Whole-exome sequencing identified a homozygous splice-site variant in the ASNS gene. Oral L-asparagine supplementation was initiated at 5 months of age (50 mg/kg/day and increased to 100 mg/kg/day after one week). A reduction in seizure frequency was observed following treatment initiation; however, this finding should be interpreted cautiously because it coincided with changes in antiepileptic therapy. No meaningful neurodevelopmental progress was observed during follow-up. ASNSD should be suspected in patients with progressive microcephaly and early-onset epilepsy despite normal metabolic screening, and CSF amino acid analysis is valuable for diagnosis. Although a reduction in seizure frequency was observed following L-asparagine supplementation in our patient, this finding should be interpreted cautiously because phenobarbital was discontinued and topiramate therapy was initiated during the same period. Therefore, the therapeutic efficacy of L-asparagine supplementation remains uncertain, and its impact on neurodevelopment appears limited.
Graph theory provides a promising technique to investigate Alzheimer's disease (AD)-related alterations in brain network properties. However, there are discrepancies in the reported disruptions that occur to network topology across the AD continuum. In this study, we examined whether diagnostic group differences in graph metrics are attributed to differences in denoising approach used in fMRI processing. Resting state data from 60 cognitively normal (CN), 55 Mild Cognitive Impairment (MCI), and 38 AD participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were denoised using 11 pipelines including combinations of confound regression (head motion parameters, white matter [WM], cerebrospinal fluid [CSF], global signal), volume censoring (scrubbing, spike regression), and component-based noise removal (Independent Component Analysis-based Automatic Removal of Motion Artifacts [ICA-AROMA], anatomical and temporal component correction). Graph metrics representing network segregation (clustering coefficient, modularity, local efficiency), network integration (largest connected component, path length, global efficiency), and small-worldness were calculated. The results revealed that diagnostic group differences in modularity and local efficiency were dependent on denoising approach, especially in high-parameter regression models in combination with censoring methods (36 parameters and spike regressor or volume censoring). Independent of denoising approach, CN exhibited more segregated (clustering coefficient) but less integrated (largest component, path length, global efficiency) networks than MCI and AD. Independent of diagnosis, denoising strategy significantly affected the magnitude of all metrics, particularly models including global signal regression. Collectively, these results suggest that the directionality of the diagnostic differences in network topology, particularly in global metrics of network segregation, can vary based upon the denoising approach employed, although the effect size is small. Transparent reporting of preprocessing decisions is critical for the accurate interpretation of graph theoretical findings in the context of AD and a better understanding of the mechanisms underlying pathological aging.
The PROMISE Registry is a U.S. decentralized, 20-year prospective prostate cancer germline genetic registry. Here, we examine the effectiveness of different recruitment strategies, including institutional partnerships, direct-to-patient marketing outreach, and community engagement grants (CEGs). Recruitment efforts were categorized into: (1) Institutional outreach through physician referrals, (2) Direct-to-patient marketing outreach, through online vehicles, including a PROMISE website and sponsored content, webinars, media relations, and other efforts to drive traffic to this site. Events and conferences were used on a limited basis, and (3) CEGs supported local organizations in reaching disproportionately affected populations. Effectiveness of each category was assessed through enrollment data, demographic diversity, and overall cost. From May 2021 to December 2024, 5649 individuals enrolled. Marketing outreach ​accounted for 61% of enrollment compared to other outreach methods. Non-White and Hispanic individuals consisted of 9.4% and 2.3%, of all consented participants, respectively. Almost one-fifth (19%) of participants enrolled were estimated to face greater levels of disadvantage, as defined by the Area Deprivation Index (ADI). A multifaceted recruitment approach was key to exceeding recruitment goals. Online marketing and strategic partnerships with patient advocacy organizations were effective and impactful. Opportunities for future research may explore refinements in digital outreach and ways to overcome accessibility barriers to improve rates of engagement and proportional representation in clinical registries.