Publications by Year: 2026

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic had direct effects on population health through infection and morbidity, as well as indirect effects on population mental health. We estimated the network structure of post-traumatic stress symptoms (PTSS) and depressive symptoms throughout the pandemic in Korea and aimed to identify the most central and bridging symptoms.

METHODS: Participants aged 30-64 years completed mental health surveys across 3 phases of the COVID-19 pandemic: March 2020 (n=1,925), February-March 2021 (n=1,754), and December 2021-January 2022 (n=1,595). Using PTSS and depressive symptom data, we conducted network analyses, and the primary measures of symptom importance (centrality) were expected influence and bridge expected influence.

RESULTS: In the comorbidity network, although the most central symptoms fluctuated over the course of the pandemic, sleep problems were consistently identified as the most influential bridge symptoms throughout. The symptom network structure differed between the subacute and chronic phases of the pandemic.

CONCLUSIONS: We found evidence of changes in the network structure of PTSS and depressive symptoms, even as sleep problems retained a consistent role as a bridging symptom. Although overall network structures varied across phases of the pandemic, the bridging role of sleep-related symptoms remained consistently strong, suggesting that sleep problems may represent a general and enduring mechanism underlying PTSS-depression comorbidity. During future pandemics, prompt screening for sleep problems may help prevent the development of comorbidity between PTSS and depressive symptoms.

Hypertrophic cardiomyopathy (HCM) is a common, often genetic, cardiomyopathy that is characterized by substantial heterogeneity. Cardiovascular magnetic resonance (CMR), with its high spatial resolution and tomographic imaging capability, has emerged as an imaging modality particularly well suited to characterize the diverse phenotypic expression in this disease. CMR allows for accurate diagnosis of HCM and differentiating HCM from other causes of left ventricular (LV) hypertrophy. CMR plays a critical role in risk stratification and prevention of sudden death in HCM, identifying important risk markers including massive LV hypertrophy, LV apical aneurysms, end-stage HCM, and extensive late gadolinium enhancement, with one or more of these risk markers is associated with a higher risk of sudden death and deserving consideration for primary prevention implanted cardioverter defibrillators. CMR also aids in management of LV outflow obstruction by defining outflow tract anatomy and guiding pre-procedural surgical planning for surgical septal myectomy. The 20-year experience of CMR in HCM has helped transform HCM into a contemporary treatable disease associated with low mortality rates for the vast majority of patients.

Most bacterial pathogens are polylysogens, harbouring multiple vertically transmitted prophages1-3. These prophages enhance bacterial pathogenicity and survival by encoding virulence factors and anti-phage defence systems while retaining the capacity for horizontal transfer. Thus, prophage-encoded anti-phage defences must block propagation of external phages without inhibiting the spread of the prophages that encode them. Here we identify HepS-an abortive infection system encoded on the Gifsy-1 prophage constituted of a single HEPN domain protein-which restricts phages of the Siphoviridae family. We demonstrate that in its native host context of Salmonella enterica serovar Typhimurium, HepS both senses phage infection and enacts abortive infection. Structures of HepS reveal a tetrameric nuclease complex that undergoes allosteric activation upon recognition of Siphoviridae tail tip proteins during production of new phage particles. Once activated, HepS cleaves specific transfer RNA anticodon loops and arrests phage replication. Gifsy-1, a Siphoviridae itself, evades self-targeting by expressing a tail tip variant that does not trigger HepS, as do co-resident Siphoviridae prophages Gifsy-2 and Gifsy-3. This evasion permits Gifsy-1 to spread despite encoding HepS. These findings reveal a mechanism by which a prophage defends the host while maintaining its propagation abilities.

Cranial nerves densely innervate the heart and vasculature, with sensory neurons reporting on blood pressure, respiratory gases and tissue damage1. The roles of arterial baroreceptors in systemic physiology are well appreciated2, but the functions of vagal cardiac mechanoreceptors have been more difficult to parse, in part due to the closed-loop structure of the cardiovascular system. Here we use genetic tools in mice to identify a small group of neurons that are acutely sensitive to circulating blood volume and initiate a reflex that compensates for decreased filling of the heart in an upright posture and haemorrhage. Vagal PIEZO2 neurons form characteristic end-net endings in the heart, lower blood pressure in response to optogenetic stimulation and display blood-volume-dependent responses with every heartbeat that are time-locked to atrial and ventricular systole. Knockout of Piezo2 and/or ablation of PIEZO2 neurons in vagal ganglia eliminates this heartbeat-coupled nerve activity, causes orthostatic hypotension and compromises cardiovascular stability during trauma-induced blood loss. Together, these findings demonstrate that vagal mechanoreceptors monitor the cardiac cycle and initiate a blood-volume-dependent reflex that defends the constancy of circulation.

Human genetic variation influences all aspects of our biology, including the oral cavity1-3, through which nutrients and microbes enter the body. Yet it is largely unknown which human genetic variants shape a person's oral microbiome and potentially promote its dysbiosis3-5. We characterized the oral microbiomes of 12,519 people by re-analysing whole-genome sequencing reads from previously sequenced saliva-derived DNA. Human genetic variation at 11 loci (10 new) associated with variation in oral microbiome composition. Several of these related to carbohydrate availability; the strongest association (P = 3.0 × 10-188) involved the common FUT2 W154X loss-of-function variant, which associated with the abundances of 58 bacterial species. Human host genetics also seemed to powerfully shape genetic variation in oral bacterial species: these 11 host genetic variants also associated with variation of gene dosages in 68 regions of bacterial genomes. Common, multi-allelic copy number variation of AMY1, which encodes salivary amylase, associated with oral microbiome composition (P = 1.5 × 10-53) and with dentures use in UK Biobank (P = 5.9 × 10-35, n = 418,039) but not with body mass index (P = 0.85), suggesting that salivary amylase abundance impacts health by influencing the oral microbiome. Two other microbiome composition-associated loci, FUT2 and PITX1, also significantly associated with dentures risk, collectively nominating numerous host-microbial interactions that contribute to tooth decay.

Cancer is a leading cause of death and its incidence is rising among younger populations, yet formal cancer education is rarely included in U.S. high school curricula. Adolescence is a critical period for establishing lifelong health behaviors, and emerging evidence suggests that school-based cancer education can improve knowledge, shift attitudes, and promote risk-reducing behaviors. In this narrative review, we summarize studies of high school and middle school cancer education programs, including curricula focused on cancer biology, modifiable risk factors (e.g., tobacco, alcohol, diet, physical activity, ultraviolet exposure), HPV vaccination, and symptom awareness. Across diverse settings, brief classroom interventions, interactive modules, and service-learning projects consistently increased cancer literacy, recognition of warning signs, and intentions to adopt preventive behaviors, with some reports of early behavior change. We further highlight the potential of cancer education to address health inequities by improving health literacy, reducing stigma, and fostering trust in the medical system, particularly in communities with limited access to care or who are at significant risk of financial toxicity. Finally, we outline pragmatic strategies for integrating cancer content into existing science, health, and social science courses; leveraging electives and clubs; and partnering with healthcare professionals and community organizations. Integrating cancer education into high school represents a feasible, equity-promoting strategy to reduce future cancer risk.

Circulating extracellular vesicles can be used for tumour diagnostics. However, current isolation methods are time consuming, require manual handling and are prone to contamination. Here we report on SpinEx (separation-processing integration for extracellular vesicles), a compact disc device for automatic isolation and multiplex immunolabelling of whole-blood samples. SpinEx integrates on-disc chromatography, centripetal liquid transfer and bead-based vesicle capture with antibody labelling. The system processes 150 µl of whole blood, enriching and labelling vesicles for 16 protein targets in under 75 minutes. Detection is performed by measuring dual fluorescence signals from labelled extracellular vesicles captured on microbeads. In a pilot clinical study, SpinEx was used to process 221 plasma samples for multiplex profiling of 30 vesicle-associated proteins. Using fluorescence flow cytometry to analyse cancer-specific biomarker expression, we found that vesicles processed by SpinEx distinguished cancer from non-cancer samples with 90% accuracy and 97% specificity, and classified 5 tumour types with 96% accuracy. SpinEx enables automated and multiplex processing of extracellular vesicles from blood, which may support the development of clinically viable assays for cancer detection and classification.

BACKGROUND: Disparities exist in alcohol use disorder (AUD) diagnosis, morbidity, and mortality based on patient demographics. Medications for alcohol use disorder (MAUD) have been demonstrated to improve AUD outcomes, and multiple agents are approved for this indication by the Food and Drug Administration (FDA). Hospitalizations are opportunities for MAUD prescribing. This study identifies race, ethnicity, and language-based differences in discharge MAUD prescribing at an academic medical center.

METHODS: This was a retrospective cohort study of adult hospitalizations with alcohol withdrawal syndrome from 2016 to 2024 at an academic medical center with an addiction consult service. Patients without an encounter in the health system within the preceding 12 months were excluded. We determined the prevalence of prescriptions for FDA-approved MAUD (oral and injectable naltrexone, acamprosate, disulfiram) on discharge and identified variables associated with discharge MAUD in generalized linear models.

KEY RESULTS: There were 5551 hospitalizations representing 2564 unique patients, with 77% of hospitalizations including an evaluation by the addiction consult service. Prevalence of discharge MAUD prescriptions was 35%. Adjusted for covariates, increased rates of discharge MAUD prescriptions were associated with Hispanic ethnicity (aRR: 1.23, 95% CI: 1.06-1.42, vs. White non-Hispanic), Black non-Hispanic race/ethnicity (aRR: 1.25, 95% CI: 1.06-1.48, vs. White non-Hispanic), and non-English language preference (aRR: 1.35, 95% CI: 1.17-1.54, vs. English preference).

CONCLUSIONS: These findings suggest that structured hospital-based addiction services may help mitigate disparities in AUD treatment by expanding equitable access to MAUD among racial, ethnic, and language minority patients.

Neurodevelopmental disorders (NDD) are a wide and heterogenous group of conditions due to impaired brain development, orchestrated by the crosstalk between genome and environment. Dynamic chromatin regulation during cortical development is fundamental, and chromatin remodelers are critical determinants of this process. Recently, numerous chromatin remodeling genes have been implicated in NDDs. By altering genes' epigenetic state, mutated chromatin remodelers disrupt the spatiotemporal regulation of gene expression during development, potentially leading to severe consequences. The Remodeling and Spacing Factor 1 (RSF1) gene encodes a ubiquitous nuclear protein involved in chromatin remodeling, crucial for processes such as DNA transcription, replication, and repair. In this study, we identified by gene matching (n = 7) and literature search (n = 4) eleven unrelated individuals harboring de novo or inherited from a symptomatic parent heterozygous variants in RSF1. All individuals had an NDD, whether intellectual disability, autism spectrum disorder or developmental delay. From the seven individuals with detailed clinical information, unspecific and inconsistent associated features were described, including cranio-facial morphological features, musculoskeletal, digestive, vision, tone, epilepsy and brain MRI anomalies. Our data support the hypothesis that RSF1 is important for brain development and a novel candidate gene for syndromic NDDs.

A tightly regulated DNA damage response is critical to the overall integrity of the genome. Here, we combine transcriptomics and proteomics to study DNA damage response kinetics across well-established treatments in the ciliate Tetrahymena thermophila This extensive data set containing six conditions (HU, MMS, IR, HP, cisplatin, and UV) and seven time points (from 0 to 8 h) integrates over 250 paired transcriptome and proteome measurements. We observe upregulation of known DNA repair proteins as well as a global dynamic response of not yet characterized transcripts and proteins. Using artificial neural networks, we classify different expression trends in response to the damaging agents. These networks reveal both a core and specific global dynamic response to the different genotoxic stressors, highlighting unexpected pathway crosstalk. In addition to the comprehensive analysis presented here, the data can be explored via an accessible user interface. Ultimately, our study provides novel insights into the DNA damage response kinetics in Tetrahymena.