Faculty Bibliography

Gramene (gramene.org) is a comprehensive reference database for comparative plant genomics and pathway analysis, integrating functional annotations, evidence-based curated pathways and their projections, and multi-omics datasets. Since our last report, Gramene has added crop-specific pan-genome portals for maize, sorghum, rice, and grapevine. These pan-genome portals host population-scale datasets and multiple assembled genomes per species, all anchored by shared reference genomes. Importantly, these portals now adopt standardized rsIDs for genetic variants, advancing FAIR data principles and enabling cross-database interoperability. The main site is now Gramene Plants, emphasizing its broad genome coverage. Release 69 features 233 reference genomes, curated pathways for 139 species, expression data from 1026 studies across 27 species, and genetic variation data mapped to 27 genomes from 19 species. Key updates to the integrated search functionality include embedded expression viewers from the Bio-Analytic Resource for Plant Biology and EMBL-EBI Expression Atlas, a literature-curated catalog of gene functions, and a new Germplasm tab linking accessions with loss-of-function alleles to seed repositories. These advances reinforce Gramene as a comprehensive platform for exploring plant genomic diversity, gene function, and evolutionary conservation across the Green Tree of Life and within key agricultural species.

Prostate MRI has transformed lesion detection and risk stratification in prostate cancer, but its impact is constrained by the high cost of the exam, variability in interpretation, and limited scalability. False negatives, false positives, and moderate inter-reader agreement undermine reliability, while long acquisition times restrict throughput. Artificial intelligence (AI) offers potential solutions to address many of the limitations of prostate MRI in the clinical management pathway. Machine learning-based triage can refine patient selection to optimize resources. Deep learning reconstruction enables accelerated acquisition while preserving diagnostic quality, with multiple FDA-cleared products now in clinical use. Ongoing development of automated quality assessment and artifact correction aims to improve reliability by reducing nondiagnostic exams. In image interpretation, AI models for lesion detection and clinically significant prostate cancer prediction achieve performance comparable to radiologists, and the PI-CAI international reader study has provided the strongest evidence to date of non-inferiority at scale. More recent work extends MRI-derived features into prognostic modeling of recurrence, metastasis, and functional outcomes. This review synthesizes progress across five domains-triage, accelerated acquisition and reconstruction, image quality assurance, diagnosis, and prognosis-highlighting the level of evidence, validation status, and barriers to adoption. While acquisition and reconstruction are furthest along, with FDA-cleared tools and prospective evaluations, triage, quality control, and prognosis remain earlier in development. Ensuring equitable performance across populations, incorporating uncertainty estimation, and conducting prospective workflow trials will be essential to move from promising prototypes to routine practice. Ultimately, AI could accelerate the adoption of prostate MRI toward a scalable platform for earlier detection and population-level prostate cancer management. EVIDENCE LEVEL: N/A TECHNICAL EFFICACY: 3.

Consumption of a western diet and high body mass index (BMI) are risk factors for progression from pre-malignant phenotypes to multiple myeloma, a hematologic cancer. In the NUTRIVENTION trial (NCT04920084), we administered a high-fiber, plant-based diet (meals for 12 weeks, coaching for 24 weeks) to 23 participants with myeloma precursor states and elevated BMI. The intervention was feasible, improved quality of life and modifiable risk factors: metabolic (BMI, insulin resistance), microbiome (diversity, composition), and immune (inflammation, monocyte subsets). Disease-progression trajectory improved (n=2) or was stable. Findings were translated to Vk*MYC mice modeling the myeloma-precursor state, in which a high-fiber diet delayed disease progression through improved metabolism and microbiome composition leading to increased short-chain fatty acid production that reinvigorated anti-tumor immunity and inhibited tumor growth. These effects from fiber consumption were independent of calorie restriction and weight loss. A high-fiber diet is a low-risk intervention that may delay progression to myeloma.

For more than 100 years, physicians and patients considered appendicitis a surgical emergency requiring hospitalization for urgent removal of the obstructed and inflamed appendix to prevent rupture and sepsis. With the advent of modern imaging, uncomplicated appendicitis is identifiable, and later evidence showed that surgical delay does not increase the risk of appendiceal perforation. Perforation appears to be a separate disease, with uncomplicated appendicitis likely related to infection, which sometimes self-resolves. Most recently, studies compared nonoperative treatment of uncomplicated appendicitis with antibiotics and observation followed by selective surgery to urgent appendectomy, including 4 multicenter trials involving more than 2,000 adults and 2,000 children. The results led the American College of Surgeons to endorse nonoperative treatment of uncomplicated appendicitis as a safe alternative treatment. Furthermore, emergency department discharge and outpatient management appears feasible in as many as 90% of nonoperative treatment of uncomplicated appendicitis-treated patients. We review methods and results of these trials and evaluate implications for emergency care.

BACKGROUND:The impact of race/ethnicity on Merkel cell carcinoma (MCC) outcomes remains inconclusive. OBJECTIVE:To examine associations between MCC primary site, virus status, environmental ultraviolet radiation (UVR), and race/ethnicity. METHODS:Patients diagnosed with MCC at the University of Washington (UW), in Surveillance, Epidemiology, and End Results (SEER-17), in National Cancer Database (NCDB), and global incidence and virus status data were included in this retrospective multi-cohort study. We estimated the prognostic effect of virus status using a Cox proportional hazards model, conducted a pooled analysis of tumor site and virus status, and investigated racial/ethnic differences in site using SEER and NCDB. We also estimated global MCC viral subtype incidences and assessed their association with geographic UV indices. RESULTS:Virus-positive MCC (VP-MCC) showed improved survival compared to virus-negative MCC (VN-MCC) (P < .001) and was more likely to develop on UV-protected skin (P < .001). Black and Hispanic patient tumors were more likely to present on UV-protected sites (P < .001). Globally, UVR had a bigger effect on VN-MCC incidence than VP-MCC. LIMITATIONS/CONCLUSIONS:Nonstandardized virus assays, unknown patient migration histories, incomplete global data, and registry selection bias. CONCLUSION/CONCLUSIONS:Black and Hispanic patients more often develop MCC on UV-protected sites, which are more likely VP-MCC and associated with improved outcomes.

This case study uses a hospital family safety reporting intervention, coproduced with key partners, with the aim to garner lessons for developing complex, hospital-based interventions. Health equity, communication science, health literacy, and organizational behavior principles were utilized to develop a family safety reporting intervention consisting of a family safety reporting tool, staff and family education, and a process for reviewing and sharing family reports with unit and hospital leaders. We evaluated intervention training rates and hospital impact (comparing family-reported safety incidents received by the hospital through voluntary incident reports at baseline to incidents received through voluntary incident reports and after the intervention). Additionally, we analyzed field notes and minutes to describe lessons learned from applying these principles in complex, hospital-based interventions. We trained 208 families, 149 nurses, 42 resident physicians, and 7 attending physicians in the intervention. After implementing the intervention, the frequency of families from whom the hospital documented safety concerns increased from an average of 0.4 per month at baseline to 4.4 per month after the intervention. Four key lessons emerged: (1) Build deep and regular partnerships across all intervention key partners, including initial skeptics. (2) Tailor the intervention message to each audience. (3) Embrace flexibility and a growth mindset when weighing suggestions and adapting interventions. (4) Equity is an investment, not a checkbox. We conclude that health equity, communication science, health literacy, and organizational behavior can inform inclusive, effective, complex hospital-based interventions but require deep partnerships, tailored messaging, flexibility, a growth mindset, and a commitment to equity.

INTRODUCTION/UNASSIGNED:Cognition is influenced by the neighborhood social and built environment, but the underlying mechanisms through which neighborhood environments affect cognition are unclear and may differ by race/ethnicity. The authors tested the hypothesis that sleep mediates the association between environmental characteristics and cognition. The authors also explored environment-sleep-cognition interrelationships separately for non-Hispanic White, non-Hispanic Black, and Hispanic older adults in the U.S. METHODS/UNASSIGNED:Analyses included older adults from Round 2 of the National Social Life, Health, and Aging Project (N=3,111). The social environment latent variable was constructed using indicators for social cohesion, social ties, and perceived neighborhood danger. The built environment was operationalized using indicators for litter, noise, traffic, pollution, and building conditions. Gross cognitive ability was characterized using the Chicago Cognitive Function Measure as an estimate of Montreal Cognitive Assessment scores. Actigraphic sleep characteristics included sleep fragmentation, time spent awake after sleep onset, and sleep percentage. RESULTS/UNASSIGNED:Participants with better cognition lived in supportive social environments and less hazardous, disruptive (e.g., noisy, polluted) built environments. The sleep mediation hypothesis was partially supported in the full sample: time spent awake after sleep onset mediated the social environment-cognition relationship, but sleep characteristics did not mediate the built environment-cognition relationship. However, in exploratory subgroup analyses, sleep mediated the social environment-cognition relationship among White older adults and mediated the built environment-cognition relationship among Black older adults. Sleep did not mediate any environment-cognition relationships among Hispanic older adults. CONCLUSIONS/UNASSIGNED:These results demonstrate that although the social and built environment influence cognition directly and indirectly through sleep, the mediational pathways may vary by specific racial/ethnic subgroups.

Evidence from rodent studies highlights the mother as a safety cue that regulates fear and biology. However, when infant rats are exposed to rough maternal care (i.e., threat), their brains show atypical patterns of activity in response to maternal cues. In humans, childhood adversity (i.e., international adoption, involvement with Child Protective Services) is also associated with differential neural responses to caregiver cues. However, to date, no studies have tested the hypothesis that childhood adversity characterized by threat (e.g., physical abuse, domestic violence) influences neural responses to caregiver cues in children, as suggested by the rodent literature. This study investigates associations between threat experiences and neural responses to caregiver cues in young children using fMRI. The sample included 148 young children (52.02% Male; M_age = 6.45 years). Across the entire sample, children demonstrated heightened recruitment in regions associated with salience detection, visual processing, and social cognition in response to caregiver cues (relative to stranger cues). Moreover, threat experiences were associated with greater recruitment of the insula in response to caregiver cues (relative to stranger cues), even when controlling for deprivation experiences. The present findings contribute to a growing field of research linking childhood adversity to brain function, suggesting that experiences of threat may disrupt how children process caregiver cues at the neural level. Moreover, these results are in line with rodent studies that underscore threat as a potential disruptor of dyadic interaction between children and their caregivers. SUMMARY: Children demonstrate widespread brain activation in response to caregiver cues. Threat experiences are linked to heightened activation of the insula, a region implicated in salience detection and primary visceral processing, in response to caregiver cues. These findings suggest that caregiver cue processing might be a mechanism through which threat impacts the caregiver-child relationship, leading to cascading effects on mental health.

BACKGROUND:Child growth failure (CGF), which includes underweight, wasting, and stunting, is among the factors most strongly associated with mortality and morbidity in children younger than 5 years worldwide. Poor height and bodyweight gain arise from a variety of biological and sociodemographic factors and are associated with increased vulnerability to infectious diseases. We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 to estimate CGF prevalence, the risk of infectious diseases associated with CGF, and the disease mortality, morbidity, and overall burden associated with CGF. METHODS:In this analysis we estimated the all-cause and cause-specific (diarrhoea, lower respiratory tract infections, malaria, and measles) disability-adjusted life-years (DALYs) lost and mortality associated with stunting, wasting, underweight, and CGF in aggregate. We combined the burden associated with mild, moderate, and severe forms of CGF: stunting was defined as height-for-age Z scores (HAZ) less than -1, underweight was defined as weight-for-age Z scores (WAZ) less than -1, and wasting was defined as weight-for-height Z scores (WHZ) less than -1, according to WHO Child Growth Standards. Population-level continuous distributions of HAZ, WAZ, and WHZ were estimated for 2000 to 2023 using data from surveys, literature, and individual-level study data. The risk of incidence of, and mortality due to, diarrhoea, lower respiratory infections, malaria, and measles was separately estimated in a meta-regression framework from longitudinal cohort data for Z scores less than -1. Finally, fatal outcomes associated with these diseases were estimated with vital registration, verbal autopsy, and case-fatality data, while non-fatal outcomes were estimated with surveys as well as health-care utilisation and case reporting data. The exposure prevalence and relative risk estimates were from continuous distributions, allowing for direct assessment of the attributable fractions for mild, moderate, and severe stunting, underweight, wasting, and the combined impact of child growth failure within populations. All estimates were age-specific, sex-specific, geography-specific, and year-specific. FINDINGS/RESULTS:We estimated that, in children younger than 5 years in 2023, CGF was associated with 79·4 million (95% uncertainty interval [UI] 47·0-106) DALYs lost and 880 000 (517 000-1 170 000) deaths. This represented 17·9% (10·6-23·8) of 444 million (434-457) total under-5 DALYs and 18·8% (11·1-25·0) of all 4·67 million (4·59-4·75) under-5 deaths. Compared to stunting (33·0 million [24·1-42·2] DALYs, 373 000 [272 000-477 000] deaths) and wasting (39·2 million [23·8-53·0] DALYs, 428 000 [256 000-583 000] deaths), childhood underweight was associated with the largest share of CGF-related disease burden: 52·2 million (21·9-75·1) DALYs and 573 000 (236 000-824 000) deaths in children younger than 5 years in 2023. INTERPRETATION/CONCLUSIONS:CGF remains a leading factor associated with death and disability in children younger than 5 years, despite global attention and focused interventions to reduce the prevalence of associated CGF indicators. Our findings underscore the need for policies, strategies, and interventions that focus on all indicators of CGF to reduce its associated health burden. FUNDING/BACKGROUND:Gates Foundation.