Citations

Vitamin D deficiency is frequently reported in hidradenitis suppurativa (HS), but its clinical significance remains unclear. In a retrospective cohort of 503 patients, deficiency was common and associated with demographic and metabolic factors but not with treatment-defined severity. Vitamin D deficiency was independently associated with elevated C-reactive protein, suggesting a link with systemic inflammation.

Abstract Background Accurate synthesis of computed tomography (CT) images from magnetic resonance imaging (MRI) is clinically valuable for cranial applications such as attenuation correction, radiotherapy planning, and image‐guided interventions. However, the heterogeneity of MRI data across magnetic field strengths and pulse sequences limits the generalizability of existing methods, posing a barrier to clinical translation. Purpose This study aims to reformulate cranial CT synthesis as a modular, structurally coupled problem using a deep learning approach, enhancing adaptability across heterogeneous MRI conditions, including different field strengths and sequence protocols. Methods We implemented a cascaded multitask pipeline that jointly models skull segmentation and Hounsfield Unit (HU) regression in anatomically targeted regions. A 3D patch‐based training paradigm shifts the modeling focus from global image translation to localized bone feature extraction. The backbone leverages a residual Mamba‐based state space model within a 3D U‐Net structure to improve spatial representation, while a Transformer U‐Net serves as a widely recognized reference baseline comparison. The model was trained and evaluated in terms of multi‐modal (T1‐weighted and T2‐FLAIR) and cross‐domain transferability from a public 1.5 Tesla brain dataset ( n = 37) to an independent 7 Tesla clinical brain dataset ( n = 44). Performance was assessed using Dice and Jaccard indices for segmentation accuracy and mean absolute error (MAE) for HU regression. Results Quantitative analysis showed that our multitask pipeline, incorporating both morphological and HU map prediction stages, significantly outperformed conventional direct MRI‐to‐CT mapping across all metrics on the public 1.5T dataset (p < 0.05). Consistent performance on an external 7T clinical dataset (p < 0.001) further demonstrated the method's robustness and adaptability across field strengths. Conclusion These findings support that task‐structured training for modality transformation markedly improves both accuracy and generalizability of cranial CT synthesis across heterogeneous MRI conditions. The observed consistency across field strengths validates the robustness of the proposed methodology.

Abstract Pancreatic cancer disproportionately affects Black individuals in the United States, but they have limited representation in genetic studies of pancreatic ductal adenocarcinoma (PDAC). To address this gap, we performed admixture mapping and genome-wide association analysis (GWAS) in genetically inferred African ancestry individuals (1,030 cases and 889 controls). Admixture mapping identified three regions with a significantly higher proportion of African ancestry in cases compared to controls (5q33.3, 10p1, 22q12.3). GWAS identified a genome-wide significant association at 5p15.33 ( CLPTM1L , rs383009:T>C, T Allele Frequency=0.51, OR:1.45, P value=1.24×10 -8 ), a locus previously associated with PDAC. Known loci at 5p15.33, 7q32.3, 8q24.21 and 7q25.1 also replicated (P value <0.01). Multi-ancestral fine-mapping identified two potential causal SNPs (rs3830069 and rs2735940) at 5p15.33. Collectively these findings identified novel PDAC risk loci and expanded our understanding of this deadly cancer in underrepresented populations, emphasizing the multifactorial nature of PDAC risk including inherited genetic and non-genetic factors. Statement of Significance To understand how genetic variation contributes to PDAC risk in Black people in North American, we studied individuals of genetically-inferred African ancestry. We identified novel risk loci and differences in the contribution of known loci. This demonstrates that ancestry-informed genetic analyses improve our understanding of PDAC risk and enhances discovery.

Abstract Background The increased use of superior mesenteric artery (SMA) divestment has been a driver behind the increased resection rate for locally advanced pancreatic cancer following preoperative therapy. This has also resulted in an increase in the rate of postoperative neurogenic diarrhoea, but knowledge about postoperative neurogenic diarrhoea is lacking. The aims of this study were to determine the incidence, risk factors, management, and outcomes of neurogenic diarrhoea after SMA divestment/resection for pancreatic adenocarcinoma. Methods This multicentre retrospective study included consecutive patients undergoing pancreatic adenocarcinoma resection, including SMA divestment/resection, after preoperative chemotherapy with or without radiotherapy between 2016 and 2022. Primary endpoints were the incidence of postoperative neurogenic diarrhoea, associated factors, treatment strategies, and outcomes. Secondary endpoints were the rate of adjuvant chemotherapy and the impact of neurogenic diarrhoea on overall survival (OS). Results Overall, 291 patients who underwent pancreatic resection with concomitant SMA divestment (240, 82%) or resection (51, 18%) were included in the study. Postoperative neurogenic diarrhoea was diagnosed in 193 patients. The adjusted risk of developing neurogenic diarrhoea was 59% (95% confidence interval (c.i.) 46 to 73) after ≤ 180° SMA divestment, 80% (95% c.i. 67 to 93) after &gt; 180° SMA divestment, and 77% (95% c.i. 66 to 88) after SMA resection. Postoperative neurogenic diarrhoea was treated with non-opioid drugs (29, 15%), non-opium opioids (140, 73%), opium tincture (69, 36%), and/or octreotide (49, 25%), and normalized in 51% of patients. After adjusting for confounders, neurogenic diarrhoea was not significantly associated with OS (hazard ratio 0.83; 95% c.i. 0.55 to 1.25). Conclusion Neurogenic diarrhoea occurred in two-thirds of patients following resection of pancreatic adenocarcinoma with concomitant SMA divestment/resection, particularly after &gt; 180° SMA divestment or SMA resection. Although challenging to manage, neurogenic diarrhoea is not associated with impaired OS. Evidence-based treatment strategies are needed for adequate management.

Abstract Background: Up to 50% of patients with breast cancer experience chemotherapy-inducednausea (CIN) and 95% experience fatigue. A comprehensive understanding of biological mechanisms remains elusive. Herein, we evaluated the association of CIN and fatigue with clinical and multi-omics features, including serum and stool metabolites before (T1) to after chemotherapy (T2). Methods: Patients with breast cancer (n=36) who were to receive chemotherapy, provided symptom assessment using the Memorial Symptom Assessment Scale, stool and blood samples at T1 and T2. Patients provided dietary intake data using a Dietary Screener Questionnaire at T1. Descriptive and univariate analyses evaluated associations of co-occurringsymptoms and diet with CIN and fatigue at T2. Gut microbiome was sequenced using shotgun metagenomics. Targeted metabolomics was performed on stool and serum. Shift in the abundance of taxonomic groups and metabolite levels from T1 to T2 were evaluated in association with CIN and fatigue. Results: Approximately 64% of the patients experienced CIN and 94% experienced fatigue atT2. Three gastrointestinal symptoms co-occurred with CIN and fatigue. Higher daily average intake of calcium (p=0.013) and dairy (p=0.035) were associated with CIN. Levels of hexosylceramides, ceramide, phosphatidylcholine and sphingomyelins were significantly perturbed in association with CIN and fatigue (p&lt;0.05). Conclusion: CIN and fatigue are associated with perturbation in the sphingolipid turnover pathway, which negatively impacts functions in the gut-liver axis that include apoptosis activity and change in bile acid levels. Confirmatory studies are warranted to support the development of interventions to alleviate CIN and fatigue in patients with breast cancer receiving chemotherapy.Keywords: breast cancer; chemotherapy-induced nausea; fatigue; metabolites; sphingolipids Citation Format: Komal Preet Singh, Brenda J. Ernst, Jun Chen, Surendra Dasari, Felipe Batalini, Cindy Tofthagen, Kathryn J. Ruddy, Keenan Pituch, Linda Chlan. Perturbations in gut liver axis functions are associated with chemotherapy induced nausea and fatigue in patients with breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6309.

Abstract BACKGROUND: Tumor-specific T cells are often characterized by reduced TCR signaling due to central and peripheral tolerance pathways that limit their responsiveness. These signals are further weakened by insufficient co-stimulation and active co-inhibitory pathways, collectively establishing a high threshold for activation. The integration of antigen recognition with co-stimulatory and inhibitory cues ultimately determines whether a T cell becomes activated or remains tolerant. Early TCR signaling must therefore be precisely regulated to prevent autoreactivity while still supporting protective immunity. Although phosphorylation and ubiquitination are well-established regulators of proximal TCR signaling, additional post-translational mechanisms remain less defined. SIRT2, a cytosolic NAD+-dependent deacetylase with emerging roles in immune regulation, has not been examined in the context of TCR signaling. METHODS: We evaluated proximal TCR signaling events in wild-type and SIRT2-deficient T cells using flow cytometry, immunoblotting, calcium flux assays, and RNA-sequencing. SIRT2-associated pathways were defined by mapping its interactome and acetylated substrates through mass spectrometry and immunoprecipitation. We screened LCK post-translational modifications by mass spectrometry and assessed SIRT2 enzymatic activity using an HPLC-based deacetylase assay. Conformational effects of LCK modification were examined using fluorescence-polarization binding assays and AlphaFold structural modeling. SIRT2 was deleted in human tumor infiltrating lymphocytes (TILs) via CRISPR/Cas9, and the impact of SIRT2 targeting was tested in lung cancer patient-derived xenograft models reconstituted with autologous TILs. RESULTS: SIRT2 deficiency amplified proximal TCR signaling, leading to elevated phosphorylation of early signaling mediators and increased calcium flux in both naïve and anergic T cells. Loss of SIRT2 also altered thymic selection dynamics and expanded TCR repertoire diversity. Mechanistically, SIRT2 interacted with and deacetylated LCK, the initiating kinase of proximal TCR signaling. Mass spectrometry identified lysine K228 in the LCK linker region as a SIRT2-regulated deacetylation site that governs LCK conformation and kinase activity. Functionally, SIRT2 inhibition in exhausted mouse and human TILs restored TCR signaling capacity and improved anti-tumor responses. CONCLUSION: Here we identify SIRT2-regulated deacetylation of LCK as a previously unrecognized mechanism that sets the strength and threshold of proximal TCR signaling. Accordingly, SIRT2 targeting reverses the exhausted phenotype of tumor-reactive T cells. Citation Format: Imene Hamaidi, Pingyan Cheng, Soo Young Jun, Min-Hsuan Wang, Min Zhang, Odesha Taylor, Luis Lopez-bailon, Ismail Can, Bin Fang, Anders Berglund, Bradford Perez, Ben Creelan, Andriy Marusyk, Virginia Shapiro, Haitao Ji, Jose R. Conejo-Garcia, Sungjune Kim. Sirt2 dictates TCR activation thresholds through post-translational control of LCK conformational state [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4250.

Abstract Background: Epidemiologic and other studies have identified environmental, occupational, and genetic risk factors for lymphoid and myeloid malignancies, but most studies have been conducted in Western populations. Investigations in populations with differing exposure patterns, distributions of disease subtypes, and genetic architecture are needed to fully understand hematopoietic tumor etiology. Methods: We conducted a large, multicenter, hospital-based case-control study of lymphoid and myeloid neoplasms in East Asia (AsiaLymph), including 5,671 lymphoid cases, 1,879 myeloid cases, and 3,858 controls. Participants completed a computer-assisted personal interview and provided biospecimens. Cases underwent central pathology review and were coded into the WHO Classification. Herein, we describe the study methods in detail and report association results for education, body mass index, and family history. Results: Greater BMI at age 20 but not at age 40 was associated with odds of total lymphoid neoplasm (per 5 kg/m2 increase: OR [95% CI]: 1.18 [1.09-1.27]), total myeloid neoplasm (OR [95% CI]: 1.17 [1.05-1.29]), and several subtypes. Greater educational attainment was associated with increased odds of total lymphoid neoplasm (for college vs. less than primary education: OR [95% CI]: 1.41 [1.21-1.65]) but not myeloid neoplasm (OR [95% CI]: 1.17 [0.95-1.45]; p-heterogeneity=0.02). There were also positive associations between family history of hematologic cancer in first degree relatives and odds of lymphoid neoplasm (OR [95% CI]: 1.53 [1.15-2.03]) and myeloid neoplasm (OR [95% CI]: 1.65 [1.11-2.44]) and specific subtypes. None of the evaluated risk factors were associated with NK/T-cell lymphoma, which supports a distinct etiology for this subtype. Conclusion: The AsiaLymph Study is one of the largest molecular epidemiology studies of both lymphoid and myeloid neoplasms with standardized World Health Organization classification of histopathologic subtypes and will serve as a valuable resource for etiologic investigations into risk factors for these malignancies. Citation Format: Qing Lan, Lauren M. Hurwitz, John K. Chan, Tai Hing Lam, Kexin Chen, Yok Lam Kwong, Xu Caigang, Brian CH Chiu, Raymond Liang, Ip Dennis, Wei Hu, Bryan Bassig, Mark Purdue, Jun Xu, Sarah Locke, Sophia S. Wang, James R. Cerhan, Sonja Berndt, Jonathan N. Hofmann, Jianxin Shi, Kai Yu, Shahinaz Gadalla, Lisa J. McReynolds, Rena Jones, Hongji Dai, Zhangyan Lyu, Lugui Qiu, Wei Liu, Huilai Zhang, Xianhuo Wang, Lindsay M. Morton, Stephen Chanock, Martha Linet, Melissa C. Friesen, Roel Vermeulen, Nathaniel Rothman. A multi-center hospital-based case-control study of lymphoid and myeloid neoplasms (AsiaLymph): Study design and initial findings for education, body mass index, and family history [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5051.

Abstract Background: Aberrations in telomere length have important implications in cancer development and progression. This study aimed to determine whether leukocyte telomere length (LTL) in patients with colorectal cancer (CRC) is associated with survival outcomes. We also investigated whether genetic variants in telomere maintenance genes are associated with survival in these patients. Methods: Blood specimens were collected from 1,007 patients prior to receiving chemotherapy or radiation. Genomic DNA was extracted using the Promega Maxwell RSC instrument. LTL was measured in triplicate using monochrome multiplex PCR, where the average amplification value of telomeric repeats was termed T. Similarly, PCR amplification of a single-copy reference gene was performed, and its average amplification value was termed S. The telomere length for each sample was expressed as the T/S ratio. Genotyping of single-nucleotide polymorphisms (SNPs) in TERC, TERT, and OBFC1 genes was conducted at the institutional Genome Analysis Core facility. Kaplan-Meier survival curves were generated to evaluate patient survival outcomes. Results: Younger individuals (∼25 years) exhibited nearly a twofold longer LTL compared with older individuals (∼75 years). No significant difference in LTL was observed between stage II and stage III CRC patients. A strong inverse correlation was observed between patient age and LTL (Spearman’s r = -0.48; p = 1.13 × 10-58). Females had significantly longer LTL than males (p = 3.97 × 10-5). The TERC SNP rs1317082 was significantly associated with both overall survival (OS) and disease-free survival (DFS) in the combined stage II and stage III patient cohort (p = 0.017 and p = 0.023, respectively). Similarly, the OBFC1 SNP rs9419958 was significantly associated with OS (p = 0.016). Importantly, LTL itself was significantly associated with both OS and DFS (p = 0.008 and p = 0.044, respectively) among the combined stage II and stage III patients. Kaplan-Meier survival analyses demonstrated that age- and sex-adjusted LTL was predictive of long-term survival outcomes. Conclusions: Survival among patients with stage II and III colorectal cancer is significantly influenced by LTL. Additionally, specific allelic variants of telomere maintenance genes, including TERC and OBFC1, are independently associated with improved survival, irrespective of LTL. These findings suggest that peripheral blood LTL measurement, along with telomere-related genotyping, may serve as a valuable prognostic marker for colorectal cancer outcomes. Funding: Individualizing colorectal cancer patient care using the host and tumor telomere phenotype (RO1 CA204013), Curtiss Fund (92541775), C-SiG Core(s): Epigenomics & Spatial Biology Core, and Clinical Core of the Mayo Clinic Center for Cell Signaling in Gastroenterology (P30DK084567) Citation Format: Estela M. Cruz Garcia, Gobinda Sarkar, Jun Chen, Shubham Sood, Kim Kossick, Daniel Schupack, Rondell Graham, Brooke Druliner, Zahra Heydari, Lauren Helgeson, Richard G. Cawthon, Lisa A. Boardman. Longer leukocyte telomeres and specific alleles of telomere maintenance genes are independently associated with improved survival of colon cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1919.