Chen, Xuan

800 Background: Primary squamous cell carcinoma (SCC) of the small intestine is exceedingly rare and associated with poor prognosis. Literature is currently limited to a few case reports, and, to our knowledge, this is the first population-based analysis of patients with small intestine SCC. This study aimed to identify patient demographics and predictors of survival outcomes. Methods: Patients with histologically confirmed primary SCC of the small intestine diagnosed between 2000 and 2022 were identified from the SEER database; autopsy-only cases were excluded. Patient demographics, tumor site, stage (SEER summary stage), and initial treatments were summarized. Overall survival (OS) was defined from diagnosis to death, with one-year OS estimated by Kaplan–Meier methods. Multivariate Cox proportional hazards models evaluated associations between patient variables (age, sex, race, residence, year of diagnosis, surgery, and chemotherapy) and mortality. All statistical analyses were performed using R version 4.4.2. Results: A total of 89 patients diagnosed with primary small intestine SCC were identified. The median age at diagnosis was 68 years; 43 % were female, and 67 % were non-Hispanic White. Most patients (82 %) resided in urban counties. Tumor site was mostly the duodenum (37 %), followed by ileum (16 %) and jejunum (10 %); 33 % were not otherwise specified. Among patients with a recorded stage, 45 % had localized disease, 38 % regional disease, and 17 % distant metastases. Initial treatment comprised surgery in 60 % of patients, chemotherapy in 25 %, and radiation in 10%. The median OS was approximately six months, and the one-year OS was 36.7 % (95 % CI 27.9–48.3). Women had a higher one-year OS (42 %) than men (33 %), although this difference was not statistically significant. In multivariable analysis, surgical resection was associated with a markedly lower hazard of death (HR = 0.43, 95 % CI 0.25–0.74). Chemotherapy was associated with an insignificantly improved survival (HR 0.54, 95 % CI 0.27–1.09). Additionally, rural residence (HR ≈ 2.9) and older age (HR ≈ 1.03) were independently associated with worse survival (p<0.05). Conclusions: This population-based study highlights the rarity and aggressiveness of primary small bowel SCC, with a median OS of six months. Surgical resection was strongly associated with improved survival (adjusted HR ≈ 0.43), reinforcing its role as the cornerstone of management. Chemotherapy showed a nonsignificant survival benefit, highlighting the need for prospective studies. The association of rural residence with higher mortality suggests disparities in access to care and underscores the need for strategies to improve early detection and referral. Overall, these findings support a multimodal approach centered on surgery and warrant further studies to elucidate pathogenesis and optimize systemic therapy.

Abstract Background Most existing biomarkers for Alzheimer's disease (AD) inform on core AD pathologies in the central nervous system, namely amyloid, tau and neurodegeneration (ATN). However, molecular disease mechanisms underlying AD are complex and heterogeneous, highlighting the need for cost‐effective blood‐based biomarkers that reflect brain molecular changes in AD beyond ATN. Method Using peripheral blood transcriptome data from the Mayo Clinic Study of Aging(MCSA) and the Alzheimer's Disease Neuroimaging Initiative, we identified genes associated with AD or mild cognitive impairment (MCI) diagnosis, cognitive, and harmonized neuroimaging measures in two cohorts, followed by meta‐analysis. We identified consensus gene co‐expression modules in MCSA and ADNI using WGCNA and assessed the association between module eigengenes and aforementioned measures. Using seven bulk brain RNAseq cohorts, we confirmed the preservation of coexpression modules across blood and brain. Enrichment analyses of Gene Ontology (GO) terms and cell‐types were performed using significant and/or hub genes. The MCSA transcriptome was further deconvoluted to obtain cell‐type proportions and cell‐type specific expression. Result Blood transcriptome modules M5 and M8 are upregulated in AD/MCI and associate with worse cognition, whereas M1, M10, M13, M16, and M21 are downregulated in AD/MCI and associate with better cognition. M17 associates with more microhemorrhages. Cell‐type enrichment analysis revealed that M5 is enriched in basophils, monocytes, and neutrophils; M8 in monocytes and neutrophils; M13 in natural kills cells; M17 in megakaryocytes; M21 in B cells. GO analysis shows broad consistency with the cell‐type enrichment analysis. M1, 5, and 8 are preserved in the brain network modules. From these modules, we prioritized transcripts significantly associated with at least one AD‐related phenotype in both blood and brain. Cell‐type deconvolution analysis shows that prioritized transcripts in M1 associate with better cognition and higher metabolic activity in B cells. Conclusion We identified blood transcripts and modules associated with AD/MCI, cognition, or neuroimaging, with three preserved in brain networks. These three modules represent centrally linked peripheral molecular signatures that can reveal perturbed brain pathways and cell level transcriptional changes in AD/MCI. We aim to further investigate the prioritized transcripts in additional datasets to establish them as potential novel biomarkers and therapeutic targets.

Abstract Background Most existing biomarkers for Alzheimer’s disease (AD) inform on core AD pathologies in the central nervous system, namely amyloid, tau and neurodegeneration (ATN). However, molecular disease mechanisms underlying AD are complex and heterogeneous, highlighting the need for cost‐effective blood‐based biomarkers that reflect brain molecular changes in AD beyond ATN. Method Using peripheral blood transcriptome data from the Mayo Clinic Study of Aging(MCSA) and the Alzheimer's Disease Neuroimaging Initiative, we identified genes associated with AD or mild cognitive impairment (MCI) diagnosis, cognitive, and harmonized neuroimaging measures in two cohorts, followed by meta‐analysis. We identified consensus gene co‐expression modules in MCSA and ADNI using WGCNA and assessed the association between module eigengenes and aforementioned measures. Using seven bulk brain RNAseq cohorts, we confirmed the preservation of coexpression modules across blood and brain. Enrichment analyses of Gene Ontology (GO) terms and cell‐types were performed using significant and/or hub genes. The MCSA transcriptome was further deconvoluted to obtain cell‐type proportions and cell‐type specific expression. Result Blood transcriptome modules M5 and M8 are upregulated in AD/MCI and associate with worse cognition, whereas M1, M10, M13, M16, and M21 are downregulated in AD/MCI and associate with better cognition. M17 associates with more microhemorrhages. Cell‐type enrichment analysis revealed that M5 is enriched in basophils, monocytes, and neutrophils; M8 in monocytes and neutrophils; M13 in natural kills cells; M17 in megakaryocytes; M21 in B cells. GO analysis shows broad consistency with the cell‐type enrichment analysis. M1, 5, and 8 are preserved in the brain network modules. From these modules, we prioritized transcripts significantly associated with at least one AD‐related phenotype in both blood and brain. Cell‐type deconvolution analysis shows that prioritized transcripts in M1 associate with better cognition and higher metabolic activity in B cells. Conclusion We identified blood transcripts and modules associated with AD/MCI, cognition, or neuroimaging, with three preserved in brain networks. These three modules represent centrally linked peripheral molecular signatures that can reveal perturbed brain pathways and cell level transcriptional changes in AD/MCI. We aim to further investigate the prioritized transcripts in additional datasets to establish them as potential novel biomarkers and therapeutic targets.