Citations

Abstract Grey matter network topology is altered in Alzheimer’s disease and these alterations are related to cognitive decline. Understanding the biological underpinnings of loss of brain connectivity may provide insights into mechanisms related to developing Alzheimer’s dementia (i.e. dementia A+). We investigated which biological processes as measured in CSF proteomics were associated with loss of brain connections across the Alzheimer’s disease continuum. We included 347 individuals with abnormal CSF amyloid [mean age ± standard deviation (SD) 66 ± 8; 98 cognitively unimpaired—A+, 88 mild cognitive impairment—A+, 161 dementia A+] and 146 cognitively unimpaired individuals with normal CSF amyloid (mean age ± SD 62 ± 8) and available T1w MRI-scans and CSF proteomic data (3097 proteins using tandem mass tag spectrometry) from the Amsterdam Dementia Cohort. We used an automated pipeline to construct grey matter networks from 3D-T1 sequences and for each network, calculated the small-worldness coefficient, which we previously found to be robustly related to cognitive decline. Linear models were applied to test associations between CSF protein levels and connectivity measures using an interaction term for clinical stage while controlling for connectivity density, age and sex. We validated our results in data from the Alzheimer’s disease Neuroimaging Initiative (ADNI). Pathway enrichment analysis was performed for proteins associated with loss of brain connectivity (P < 0.05) using the Gene Ontology database. Individuals across the Alzheimer’s disease continuum had lower small-worldness coefficients compared with controls (ANOVA P < 0.001). In amyloid positive individuals, higher levels of 222 proteins and lower levels of 482 proteins were associated with lower small-worldness coefficients and were enriched for innate immune system and neuroplasticity pathways, respectively. Stratified for disease stage, most protein associations with lower small-worldness coefficients were found in mild cognitive impairment A+ (n = 527 proteins) and dementia A+ (n = 799 proteins) with considerable overlap (n = 239 proteins). Proteins in these stages were enriched for complement activation and synaptic integrity. In cognitive unimpairment A+, we found proteins enriched for processes involved in apoptosis. We did not find any enriched biological processes in controls. Repeating analyses in ADNI indicated that similar biological processes were associated with altered grey matter network connectivity. Higher CSF levels of proteins involved in immune responses and lower levels of proteins related to neuroplasticity were associated with lower small-worldness coefficients across the Alzheimer’s disease continuum. This suggests that preserving cognitive function in the presence of amyloid and prevention of dementia A+ may require therapies that strengthen synapses and targets the innate immune system in addition to amyloid and tau.

Civic health equity is the principle that all people deserve a fair and just opportunity to participate in their communities and to have a voice in the systems that shape their lives. Yet despite its importance to population health, civic engagement remains inconsistently addressed in health professions education. Inequities in civic participation contribute to unequal political representation and policy responsiveness, disproportionately affecting historically marginalized communities, and limit the ability of future health professionals to engage with the structural and policy drivers of health. This paper describes the development and implementation of a civic health equity metric within the Planetary Health Report Card (PHRC), an international, student-led, faculty-supported initiative that evaluates how health professional schools integrate planetary health and social accountability into educational practice. First introduced in the 2026 PHRC assessment cycle, the metric was developed through iterative leadership discussions informed by existing frameworks. It assesses whether health professional curricula prepare students to understand civic participation and advocacy as mechanisms for addressing environmental and structural determinants of health. The metric is part of the PHRC curriculum domain and uses a standardized scoring system ranging from 0 to 3 points, with required qualitative justification from participating institutions. To promote feasibility and broad adoption, it is explicitly nonpartisan and educational in nature, aligning with 501(c)(3) requirements. By embedding civic health equity within an established assessment framework, this metric provides educators with a practical tool to identify curricular gaps, support equitable access to civic learning, and strengthen health promotion–oriented training.

Background: Patients with spontaneous coronary artery dissection (SCAD) are at increased risk of cardiovascular events, including dissection in other arterial territories such as cervical arteries. Those with combined coronary and cervical arterial dissection (CACAD) may have more widespread arterial abnormalities and worse outcomes, underscoring the need for better risk stratification and personalized care. Objective: This study examined the prevalence of cervical artery dissection (CvAD) in patients diagnosed with SCAD, evaluated potential risk factors for developing CvAD, and assessed their impact on clinical outcomes, including all-cause mortality, SCAD recurrence, and stroke. The goal was to enhance risk stratification by identifying SCAD patients at increased risk for CvAD. Design: In this retrospective cohort study, patients diagnosed with SCAD between 2018 and 2024 across Mayo Clinic sites were identified using ICD-10 codes. Manual chart review confirmed CvAD diagnoses. Patients were stratified based on the presence or absence of CvAD. Chi-square and independent t-tests were used to compare risk factors and comorbidities. Univariate screening and multivariable logistic regression were used to identify predictors of CvAD. Results: Among 1380 patients with SCAD, 131 (9.5%) had CvAD. The median follow-up was 2.02 years (IQR: 1.1–5.2 years). All CvAD diagnoses were identified after the index SCAD event through systematic post-SCAD vascular imaging. The mean age was similar between groups (51.5 ± 11.3 years in CACAD vs. 50.9 ± 10.7 years in SCAD-only, p = 0.540), and the majority were female (93.9% vs. 91.9%, p = 0.529). Multivariable regression identified extremity arterial dissection (OR: 8.13, 95% CI: 3.41–19.36, p < 0.001), fibromuscular dysplasia (FMD) (OR: 7.52, 95% CI: 4.67–12.10, p < 0.001), connective tissue disorders (CTDs) (OR: 6.85, 95% CI: 2.35–19.98, p < 0.001), and anxiety (OR: 1.69, 95% CI: 1.01–2.81, p = 0.044) as significant predictors of CvAD. CvAD was a strong independent predictor of stroke (OR: 6.37, 95% CI: 2.93–13.87, p < 0.001). Mortality and SCAD recurrence did not differ significantly between groups. Conclusions: Patients with CACAD demonstrate a systemic vascular phenotype with significantly higher rates of FMD, connective tissue disease, extremity arterial dissection, and stroke. These findings highlight the importance of comprehensive vascular screening and individualized monitoring in at-risk SCAD patients.

ABSTRACT Objectives Tongue base obstruction is a cause of persistent sleep apnea after adenotonsillectomy in pediatric patients. The internet is the most used tool by patients for gathering healthcare information. This study aims to assess the quality and readability of websites directed to patients regarding tongue base procedures for pediatric obstructive sleep apnea. Methods Queries for the terms “lingual tonsillectomy,” “posterior midline glossectomy,” “tongue reduction,” “tongue base suspension,” and “hypoglossal nerve stimulator” were entered into Google on September 11, 2023. Thirty sites were pulled for each, and up to 10 sites per query meeting inclusion criteria were included for analysis. The DISCERN tool was used to evaluate quality. Flesch Reading Ease Score (FRES) and Flesch–Kincaid Grade Level (FKGL) were used to measure readability. Sites were analyzed for mention of pediatrics. Results Thirty‐five unique sites were analyzed. The mean DISCERN score was 44.7 (range 28.5–64.0) or “fair.” The mean FRES was 46.3 (range 9.6–66.6) and FKGL 11.5 (range 7.4–19.2), indicating college and 12th‐grade reading levels. Only 8/35 sites mentioned pediatrics. The average number per query of relevant sites directed towards patients on the first search engine page was 3.6. Despite tongue base procedures being relevant to pediatrics, only one in five sites mentioned children. Conclusion Websites directed at patients regarding tongue base procedures are of “fair” quality and at readability grade levels far above what is recommended. The majority of sites available for tongue base procedures are geared to professionals rather than patients. This study demonstrates a need for high‐quality information for patients about these procedures.

ABSTRACT This case highlights the diagnostic challenges posed by rare oropharyngeal neurofibromas, their potential to mimic other conditions, and the novel application of transoral robotic surgery (TORS) for the management of an oropharyngeal neurofibroma. A 47‐year‐old female presented with a 1‐year history of a left tonsillar mass. Clinical evaluation, imaging, and biopsy results were inconclusive but raised suspicion for a neoplasm. The patient underwent robotic‐assisted tonsillectomy and mass resection. Subsequent histopathological evaluation confirmed a benign spindle cell tumor consistent with neurofibroma. Oropharyngeal neurofibromas may present diagnostic challenges due to their resemblance to common tonsillar pathologies. Imaging and biopsies may not always provide definitive diagnoses, necessitating surgical excision for accurate characterization. This case demonstrates the utility of TORS, offering improved visualization and access while minimizing patient morbidity.

ABSTRACT Background Artificial intelligence (AI) and automation offer opportunities to enhance the efficiency, timeliness, and sustainability of living guidelines (LGs). However, how AI and automation have been integrated into existing LG development frameworks remains unclear. This scoping review represents the first step in a broader programme of work aimed at developing a framework which aims to guide responsible and coordinated AI adoption across all phases of LG development. Objective To identify existing frameworks, methods, and approaches that integrate AI or automation into any stage of LG development. Methods We conducted a structured search of PubMed, Embase, Web of Science, Scopus, Cochrane Database for Systematic Review and Cochrane Central Register of Controlled Trials from inception to March 12, 2026. We included peer‐reviewed articles describing frameworks, models, or methods that applied AI or automation in the development of LGs. We extracted data into a standardised form, capturing study characteristics, AI methods, targeted guideline processes, and key findings and synthesised findings using a thematic narrative approach. Results Of 1090 records identified, three studies met the inclusion criteria. The included studies described AI or automation applied to select components of the LG process, to support continuous evidence surveillance, to semi‐automate study screening, and incremental updating of living systematic reviews. None addressed multiple stages of LG development in an integrated manner. Conclusions Current evidence demonstrates fragmented and narrowly focused AI or automation applications within LG development processes. Our findings highlight opportunities for future work to develop and evaluate more comprehensive frameworks that span multiple stages of the LG lifecycle.

Abstract Accurate taxonomic profiling of human microbiomes is essential for advancing research and understanding the complex role microbial communities play in human health. When using shotgun metagenomics, the sequencing data is analyzed through metagenomic pipelines, which incorporate various open-source tools and classify microbes based on matched paired-end DNA reads. However, differences in sequencing and computational approaches can produce substantially different microbiome profiles from the same sample, making validation critical. One approach for validation is benchmarking with realistic mock communities, but this remains relatively rare. Additionally, existing benchmarks often overlook microbiome variability across life stages and body sites, limiting their clinical and research utility. Here, we developed age- and body site-stratified synthetic metagenomes, enabling context-aware benchmarking of microbiome pipelines. Using novelty-based sampling to prioritize microbial diversity and minimize redundancy among selected samples, we selected 300 representative, real biological samples spanning six categories: adult, child, toddler, and infant (>6 months and <6 months) gut samples, as well as adult vaginal samples. We validated three pipelines, Tiny Health’s proprietary Metagenomic Classifier v2 (THMCv2), MetaPhlAn4, and Kraken2+Bracken, using precision, recall, F1 score, and area under the precision-recall curve (AUPR) across age groups and sample types. THMCv2 demonstrated higher recall and F1 scores, detecting more taxa across sample types and ages, while MetaPhlAn4 achieved the highest precision. THMCv2 also achieved the highest area under the precision-recall curve, reflecting peak performance across both abundant and rare species. When analyses were weighted by abundance, THMCv2 and MetaPhlAn4 each characterized the mock community nearly perfectly. Errors for THMCv2 were largely restricted to very low-abundance taxa (<0.001%), whereas MetaPhlAn4 occasionally produced false positives for higher-abundance taxa. Species-level analyses of clinically relevant microbes confirmed these patterns, with THMCv2 demonstrating higher sensitivity, MetaPhlAn4 higher specificity, and Kraken2 lower overall performance. These results demonstrate clear precision-recall trade-offs in metagenomic profiling. This benchmarking framework provides a reproducible approach for evaluating pipeline performance across diverse microbiome contexts and life stages.

Cercospora leaf spot (CLS) is a destructive disease of sugar beet (Beta vulgaris ssp. vulgaris L.) for which resistance conferred by the gene BvCR4 has been introgressed from sea beet (B. vulgaris ssp. maritima). BvCR4-mediated resistance has been broadly deployed to manage CLS globally in sugar beet; however, continuous implementation exerts strong selection pressure, increasing the risk of disease outbreaks due to resistance-breaking C. beticola populations. This study aimed to identify BvCR4 variants in public B. vulgaris spp. germplasm to assess their genetic and structural diversity. Polymerase chain reaction screening of 589 public B. vulgaris spp. germplasm detected BvCR4 homologs in 32 accessions with diverse responses to CLS including historically relevant sugar beet lines represented in breeding programs and Mediterranean sea beet populations of diverse genetic backgrounds. Analysis of the genomic sequences revealed higher diversity in sea beet compared to sugar beet. Additionally, population genetic analysis indicated that BvCR4 homologs in sugar beet likely originated from sea beet populations in Italy and Greece. We identified historical cultivated materials carrying full proteins encoded by BvCR4 alleles and delineated geographic regions where sea beet populations harbor BvCR4 homologs that may be useful in breeding programs. Structural variation was largely circumscribed within leucine-rich repeat domains, although CLS resistance phenotyping was not associated with specific polymorphisms, suggesting BvCR4-mediated resistance may rely on interactions with other co-receptors. This study provides resources for sugar beet improvement by enabling the identification of BvCR4 homologs in diverse germplasm and disclosing materials with potentially novel resistance.

ABSTRACT Clinical pharmacists are increasingly recognized as vital contributors to acute stroke care, yet their role remains inconsistently defined and underutilized across health care systems. This consensus statement explores the expanding presence of clinical pharmacists within interdisciplinary stroke teams, particularly in the management of both acute ischemic stroke ( AIS ) and hemorrhagic stroke. This consensus statement panel was composed of clinical pharmacists, emergency medicine physicians, and a vascular neurologist. The Grading of Recommendations, Assessment, Development, and Evaluation ( GRADE ) approach was used to assess the level of certainty and strength of recommendations. We focused on two questions regarding the clinical pharmacist's role in caring for adult patients presenting to the emergency department ( ED ) with AIS or hemorrhagic stroke. Despite the very low level of evidence, a consensus was reached for the following recommendations: (1) clinical pharmacist involvement in AIS care for adult patients presenting to the ED and (2) clinical pharmacist involvement in hemorrhagic stroke care for adult patients presenting to the ED . Based on the available literature, we believe optimizing the clinical pharmacist role is a critical factor in improving time‐sensitive treatment and equity in care delivery.