Digital Commons Network^™

Giant Cell Tumor Of The Bone With Fatal Pulmonary Metastasis: A Case Report, Mohamad Taha, Saadia A Faiz, Pushan Jani, Jing Liu, Yasir D Ali, Mohammad Asim Amjad

Faculty, Staff and Student Publications

Giant cell tumors of the bone are typically benign, locally aggressive lesions that rarely metastasize. In this report, we describe the case of a 48-year-old woman presenting with a giant cell tumor of the bone of the hip joint, which demonstrated aggressive histological features and recurrent behavior. The patient developed multiple unresectable pulmonary metastases despite several wide local excisions. Although pulmonary metastases from giant cell tumors of the bone are usually associated with a relatively favorable prognosis, guidelines for the optimal treatment of metastatic giant cell tumors of the bone remain limited. This case highlights the unpredictable nature of giant …

Thrombotic Storm With Antiphospholipid Syndrome In The Setting Of Relapsing Evans Syndrome And Systemic Lupus Erythematosus: A Case Report, Som Singh, Sergio Abraham Candiales, Zachary Hunzeker, Cristina Olivo Freites, Modupe Idowu

Faculty, Staff and Student Publications

Background: There are few cases that report the presence of lupus anticoagulant and antiphospholipid antibodies between Evans syndrome and the presence of lupus anticoagulant. However, differentiating between primary and secondary causes of Evans syndrome remains challenging.

Case description: A 31-year-old female with a medical history of autism spectrum disorder, antiphospholipid syndrome (APS), complete systemic lupus erythematosus (SLE), and Evans syndrome was admitted for cholecystitis requiring laparoscopic cholecystectomy. In the setting of her acute illness, her thrombocytopenia worsened. Her hospital course was then complicated by the development of a left adrenal hematoma and venous thrombosis. Anticoagulation therapy was conservatively held due …

Use Of Hookah And Age Of Asthma Onset Among Us Adults, Adriana Pérez, Sarah Valencia, Pushan P Jani, Melissa B Harrell

Faculty, Staff and Student Publications

Objective: To explore the association of hookah use on the age of asthma onset among adults who were asthma/COPD free and who did not use cigarettes, cigars, electronic cigarettes or smokeless tobacco prior to asthma onset.

Methods: Secondary data analyses were conducted of the waves 1-6 (2013-2021) of the US nationally representative Population Assessment of Tobacco and Health Study among adults (>18 years). The four hookahs use exposures evaluated were (1) past 30-day (P30D) hookah use at the first wave of participation, (2) total number of waves before asthma onset in which adults reported P30D hookah use, (3) total …

Changes In Medication Complexity And Post-Hospitalization Outcomes In Older Adults Hospitalized For Heart Failure, Aayush Visaria, William Mcdonald, John Mancini, Andrew P Ambrosy, Min Ji Kwak, Ashkan Hashemi, Mark S Lachs, Andrew R Zullo, Monika Safford, Emily B Levitan, Parag Goyal

Faculty, Staff and Student Publications

Introduction: Medication regimen complexity may be an important risk factor for adverse outcomes in older adults with heart failure. However, increasing complexity is often necessary when prescribing guideline-directed medical therapy at the time of a heart failure hospitalization. We sought to determine whether increased medication regimen complexity following a heart failure hospitalization was associated with worse post-hospitalization outcomes.

Methods: This retrospective cohort study included Reasons for Geographic and Racial Differences in Stroke (REGARDS) participants aged at least 65 years hospitalized for heart failure between 2003 and 2014. We calculated changes between hospital admission and discharge in medication count (Δcount) and …

Editorial: Women In Brain Imaging And Stimulation, Volume Ii: 2024, Molly S Hermiller, Ruogu Fang, Wen Li

Faculty, Staff and Student Publications

No abstract provided.

An Ontology-Based Method For Formalizing And Encoding Patient Colonoscopy Preparation Using Bpmn And Owl2 For Automated Tool Development, Muhammad Amith, Yue Yu, Yuheng Shi, Brooks Cash, Barani Mayilvaganan, Anirudh Babu, Yang Gong

Faculty, Staff and Student Publications

Colonoscopy is a proven procedure for mitigating the incidence of colorectal cancers in late adulthood. Despite its effectiveness, colonoscopy preparation presents several challenges for patients, including issues with adherence and misunderstanding. Information and communication technology (ICT) tools may offer valuable support for modern patients. To enable such tools, computable knowledge bases are essential. In this paper, we describe the development of an ontology-based knowledge graph representing four laxative-based pre-colonoscopy procedures. We used the business process modeling and notation and OWL2 formalisms to manifest machine-readable artifacts that model processes of colonoscopy preparation. Future work will focus on integrating extended knowledge bases …

Esomeprazole Inhibits Proliferation Of Scleroderma Fibroblasts Via Cell Cycle Regulation, Mohammad A Khan, Shaheer Koniyan, Manisha Ahir, Anil G Jegga, Maureen D Mayes, David Gius, Justin Leung, Mark D Bonnen, Sydney B Montesi, Yohannes T Ghebre

Faculty, Staff and Student Publications

Background: Scleroderma is a complex autoimmune disease characterized by abnormal fibroblast proliferation and excessive collagen deposits in the skin and internal organs. We previously showed that esomeprazole, an FDA-approved drug for gastric disorders, may prevent dermal fibrosis.

Methods: To test this, we evaluated the antiproliferative effect of esomeprazole and the underlying molecular mechanisms using primary fibroblasts derived from patients with scleroderma. BrdU incorporation, flow cytometry, immunofluorescence, Western blot analysis, RNA sequencing, and functional enrichment analysis were performed.

Results: Esomeprazole inhibited the proliferation of scleroderma fibroblasts in a dose-dependent manner, as measured by BrdU incorporation and Ki-67 marker. Intriguingly, esomeprazole arrested …

Oral Microbiome Brain Axis And Cognitive Performance In Older Adults, Darbaz Adnan, Phillip A Engen, Michelle Villanueva, Shohreh Raeisi, Vivian Ramirez, Ankur Naqib, Stefan J Green, Faraz Bishehsari, Lisa L Barnes, Ali Keshavarzian, Klodian Dhana, Robin M Voigt

Faculty, Staff and Student Publications

The human oral microbiota is a community of microorganisms that reside in the oral cavity, including lingual, buccal, and saliva, each niche with a distinct microbial composition. Alterations in oral microbiota have been associated with an increased risk of Alzheimer’s disease (AD). This study used data from 143 older adults in the MIND trial to evaluate the association between oral microbiome and cognitive function. Oral niche-specific differences (saliva, buccal, and lingual), as well as the microbiome composition differences (α and β diversity), were associated with cognitive function. A lower abundance of Gemella and a higher abundance of anaerobic pro-inflammatory bacteria …

Decline In Attrition Rates In United States Pediatric Residency And Fellowship Programs, 2007–2020: A Repeated Cross-Sectional Study, Emma Omoruyi, Greg Russell, Kimberly Montez

Faculty, Staff and Student Publications

Purpose: Declining fill rates in US pediatric residency and subspecialty programs requires trainee retention. Attrition, defined as transfers, withdrawals, dismissals, unsuccessful completions, or deaths, disrupts program function and impacts the pediatric workforce pipeline. It aims to evaluate attrition trends among pediatric residents and fellows in Accreditation Council for Graduate Medical Education (ACGME)-accredited programs from 2007 to 2020.

Methods: This repeated cross-sectional study analyzed publicly available ACGME Data Resource Book records. Attrition rates and 95% confidence intervals (CIs) were calculated overall and by subspecialty. Logistic regression assessed temporal changes; odds ratios (ORs) compared 2020 to 2007.

Results: From 2007-2020, pediatric residents …

National Landscape Of Underrepresented In Medicine Visiting Medical Student Programs In Pediatrics, Tyler K Smith, Rebecca Blankenburg, Ann E Burke, Emma A Omoruyi, Wendla Sensing, Tiffany Ruan, David D Williams, Onyi Oligbo, Lahia Yemane

Faculty, Staff and Student Publications

Objective: Underrepresented in medicine visiting medical student programs (UIM-VMSPs) have gained popularity across specialties as an intervention to diversify residency programs; however, no study has explored the national landscape of these programs in pediatrics. This study aimed to characterize program components, residency rank and match outcomes, benefits, challenges, and lessons learned about UIM-VMSPs in pediatrics nationally.

Methods: From September to December 2023, the authors conducted a national, cross-sectional, mixed methods study surveying program leaders of UIM-VMSPs identified on the Association of Pediatric Program Directors website. The authors used descriptive statistics to analyze the data and conventional content analysis for free-text …

Implantable Loop Recorder Identifies Sustained Ventricular Tachycardia In A Pediatric Patient Despite Negative Ep Study: A Case Report, Jia Yue Liu, Mohammed T Numan

Faculty, Staff and Student Publications

Experience of loop recorders in pediatric patients is limited. We report using a loop recorder to detect ventricular arrhythmias in a 16-year-old female who had years of palpitations despite inconclusive noninvasive and invasive electrophysiological testing.

Case Report: Coronary Vasospasm Precipitating Stemi And Polymorphic Ventricular Tachycardia-A Case Of Cardiotoxicity From 5-Fu Based Chemotherapy In A 41-Year-Old Woman, Ammar Hasnie, Zachary Neace, Kristin Ellison, Aaron Hesselson, Karam Ayoub, Mohammed Al-Yafi, Amit Arbune

Faculty, Staff and Student Publications

Background: Intravenous 5-fluorouracil (5-FU), in combination with oxaliplatin and folinic acid, makes up a chemotherapy regimen commonly referred to as FOLFOX. It is well-established for its efficacy in patients with advanced colorectal cancer; however, the benefits are accompanied by potential side effects that warrant careful consideration. Common toxicities can range from nausea and vomiting to neuropathy. Cardiotoxicities related to FOLFOX and fluoropyrimidines in general are extremely rare but can easily be fatal.

Case presentation: A 41-year-old woman who was recently diagnosed with stage IIIc colorectal cancer after she underwent a subtotal colectomy was admitted to the Oncology clinic for further …

Rho/Rock Pathway As A Therapeutic Target In Multiple Diseases, Zixiu Cheng, Shannon Erhardt, Jun Wang

Faculty, Staff and Student Publications

The Rho/ROCK (Rho-associated coiled-coil-containing protein kinase) signaling pathway plays a pivotal role in regulating diverse cellular processes, including cytoskeletal organization, cell migration, proliferation, and apoptosis. Dysregulation of this pathway has been implicated in the pathogenesis of various diseases, such as cardiovascular disorders, cancer, neurological conditions, and fibrotic diseases. Accumulating evidence supports the therapeutic potential of targeting Rho/ROCK, with several inhibitors currently under investigation or in clinical use. This review summarizes the molecular mechanisms underlying Rho/ROCK signaling, explores its involvement in disease progression, and discusses recent advances in the development of and the clinical application of ROCK inhibitors as promising therapeutic …

Revisiting Cytomegalovirus In Pediatric Allogeneic Hematopoietic Stem Cell Transplant Recipients: Current Strategies For Prevention And Management In The Letermovir Era, Lisa Hiskey, Diego R Hijano, Ramia Zakhour

Faculty, Staff and Student Publications

CMV infection remains the most common clinically significant infection in pediatric allogeneic hematopoietic stem cell (HCT) recipients, with seropositive recipients of transplants from seronegative donors at the highest risk for complications. In recent years, letermovir, a novel antiviral with a favorable toxicity profile, was approved first for adults and more recently for pediatric patients for the primary prophylaxis of CMV infection and disease in high-risk HCT recipients. Growing evidence from real-life data regarding the safety and efficacy of letermovir has transformed the landscape of CMV disease in HCT transplant recipients and led to a paradigm shift from a preemptive approach …

Safety Of Indocyanine Green Microdosing For Clinical Imaging Of Csf Ventricular Dynamics And Extracranial Outflow, Miriam Zamorano, Banghe Zhu, Ahmed T Massoud, Jonathan Hendricks, H Alex Choi, Pedram Peesh, Brandon A Miller, Xinhai Robert Zhang, Manish N Shah, Eva M Sevick-Muraca

Faculty, Staff and Student Publications

Background and purpose: Intravenous administration of indocyanine green (ICG) has been approved in brain surgeries for decades, yet concerns about neurotoxicity prevent its direct administration into the cerebrospinal fluid (CSF). Armed with prior animal studies demonstrating the feasibility of using ICG microdosing into the CSF, we sought to evaluate its nonclinical safety profile and obtain surrogate measures in adults prior to its use in human neonates.

Methods: Evaluation of ICG toxicity was conducted in mixed primary CNS cell cultures and in an extended safety study of juvenile rat pups deploying intraventricular injections of saline (as control) or ICG. Analysis of …

Molecular, Histologic, And Clinical Characterization Of Methylation Class Pleomorphic Xanthoastrocytoma: An Analysis Of 469 Tumors, Christopher H Dampier, Niharika Shah, Kristyn Galbraith, Azadeh Ebrahimi, Osorio Lopes Abath Neto, Zied Abdullaev, Sanda Alexandrescu, Felipe Andreiuolo, Terri Armstrong, Tiffany Baker, Sahara Cathcart, Hye-Jung Chung, Patrick J Cimino, Kyle S Conway, Jennifer Cotter, Felipe D'Almeida Costa, Karen Dazelle, Nima Etminam, Sima Esther Ferman, Igor Fernandes, Christina K Ferrone, Ahmed Gilani, Mark Gilbert, Jason Gregory, Courtney Ketchum, Han Sung Lee, Ina Lee, Maria Beatriz S Lopes, Qinwen Mao, Michael S Marshall, Matthew Mccord, Stewart G Neill, Jeffrey J Nirschl, Byram H Ozer, Werner Paulus, Marta Penas-Prado, Marco Prinz, Peter Pytel, Martha Quezado, Mark Raffeld, Sharika Rajan, Miriam Ratliff, Guido Reifenberger, Lorraina Robinson, Jens Schittenhelm, Daniel Schrimpf, Omkar Singh, Christian Thomas, Diana Thomas, Jaiyeola Thomas-Ogunniyi, Angus Toland, Rust Turakulov, Rachael Vaubel, Nitin Wadhwani, Jing Wu, Caterina Giannini, Matija Snuderl, Sebastian Brandner, Andreas Von Deimling, Kenneth Aldape

Faculty, Staff and Student Publications

Background: Methylation class pleomorphic xanthoastrocytoma (mcPXA) comprises tumors with the DNA methylation signature of classical PXA but with a wider histologic spectrum, including overlap with glioblastoma (GBM).

Methods: To clarify the histologic and molecular scope of mcPXA and characterize its clinical behavior, a cohort of 469 tumor samples from 458 patients matching to mcPXA by the DKFZ classifier (v12.6 score ≥0.85) was interrogated.

Results: Patient median age was 23 years (range 1-73 years) with a female predominance (259 female/199 male). CDKN2A/B homozygous deletion was observed in 406 of 469 (87%) samples. In samples tested for BRAF p.V600E mutations (n …

Advancing Randomized Clinical Trials In Surgery: Role Of Exception From Informed Consent, Central Institutional Review Board, And Bayesian Approaches, Amelia W Maiga, Rebecca A Snyder, Lillian S Kao, Mehul V Raval, Mayur B Patel, Martin L Blakely

Faculty, Staff and Student Publications

No abstract provided.

Reducing Computed Tomography Use For Appendicitis Evaluation In A Pediatric Emergency Department: A Multidisciplinary Quality Improvement Initiative, Jennifer Hockenbury, Monica E Lopez, Caroline M Godfrey, Martin L Blakely, Melissa Danko, Marta Hernanz-Schulman, S Barron Frazier

Faculty, Staff and Student Publications

Introduction: Appendicitis is the most common pediatric surgical emergency, and computed tomography (CT) remains an overused diagnostic test for appendicitis. Our institutional rate of CT utilization for suspected appendicitis was higher than in peer children's hospitals, so we aimed to reduce CT utilization during the evaluation of pediatric appendicitis from 31.3% to 15% within 12 months.

Methods: From September 2021 to October 2022, we conducted a multidisciplinary quality improvement initiative among patients evaluated for appendicitis in the pediatric emergency department (PED). Interventions included standardizing evaluation with a clinical practice guideline, an order set in the electronic medical record for clinical …

Moving From Prognostication To Prevention Of Ssis In Lmics, Stephanie Martinez Ugarte, Mokunfayo O Fajemisin, Lillian S Kao

Faculty, Staff and Student Publications

No abstract provided.

Enl Mutation And Aml: A New Model That Reveals Oncogenic Condensate’S Function In Leukemogenesis, Zhong Fan, Yanan Jiang, Xiaotian Zhang

Faculty, Staff and Student Publications

Precise regulation of gene expression is essential for proper development and the maintenance of homeostasis in organisms. Studies have shown that some transcriptional regulatory proteins influence gene expression through the formation of dynamic, locally concentrated assemblies known as condensates, while dysregulation of transcriptional condensates was associated with several cancers, such as Ewing sarcoma and AML [Wang Y et al. (2023) Nat Chem Biol 19, 1223-1234; Chandra B et al. (2022) Cancer Discov 12, 1152-1169]. Mutations in the histone acetylation "reader" eleven-nineteen-leukemia (ENL) have been shown to form discrete condensates at endogenous genomic targets, but it remains unclear how ENL mutations …

Three-Dimensional Deep Learning Normal Tissue Complication Probability Model To Predict Late Xerostomia In Patients With Head And Neck Cancer, Hung Chu, Suzanne P M De Vette, Hendrike Neh, Nanna M Sijtsema, Roel J H M Steenbakkers, Amy Moreno, Johannes A Langendijk, Peter M A Van Ooijen, Clifton D Fuller, Lisanne V Van Dijk

Faculty, Staff and Student Publications

Purpose: Conventional normal tissue complication probability (NTCP) models for patients with head and neck cancer are typically based on single-value variables, which, for radiation-induced xerostomia, are baseline xerostomia and mean salivary gland doses. This study aimed to improve the prediction of late xerostomia by using 3-dimensional information from radiation dose distributions, computed tomography imaging, organ-at-risk segmentations, and clinical variables with deep learning (DL).

Methods and materials: An international cohort of 1208 patients with head and neck cancer from 2 institutes was used to train and twice validate DL models (deep convolutional neural network, EfficientNet-v2, and ResNet) with 3-dimensional dose distribution, …

Anti-Cd137 Agonist Antibody-Independent And Clinically Feasible Preparation Of Tumor-Infiltrating Lymphocytes From Soft Tissue Sarcoma And Osteosarcoma, Yining Jin, Zhiliang Jia, Xueqing Xia, Nancy B Gordon, Joseph A Ludwig, Neeta Somaiah, Shulin Li

Faculty, Staff and Student Publications

Background: Tumor infiltrating lymphocytes (TILs) therapy has been proved for treatment of metastatic melanoma and is under investigation for other types of solid tumors. However, these successes are threatened by discontinued supply of GMP-grade anti-CD137 agonist, a key TIL preparation reagent. Therefore, exploring a GMP-adherent method for expanding endogenous TILs without anti-CD137 agonist is urgent. Toward this end, we aimed to establish an anti-CD137-independent and clinically feasible TIL expansion protocol to prepare TILs from under investigated sarcoma tumors.

Methods: We collected resected tumors from patients and cut tissues into fragments. We used IL-2 and T-cell activator CD3/CD28 without anti-CD137 agonist …

A Serum Biomarker Panel And Miniarray Detection System For Tracking Disease Activity And Flare Risk In Lupus Nephritis, Chenling Tang, Gongjun Tan, Aygun Teymur, Jiechang Guo, Arturo Haces-Garcia, Weihang Zhu, Richard Williams, Jing Ning, Ramesh Saxena, Tianfu Wu

Faculty, Staff and Student Publications

Introduction: Lupus nephritis (LN) leads to end stage renal disease (ESRD), and early diagnosis and disease monitoring of LN could significantly reduce the risk. however, there is not such a system clinically. In this study we aim to develop a biomarker-panel based point-of-care system for LN.

Methods: Immunoassay screening combined with genomic expression databases and machine learning techniques was used to identify a biomarker panel of LN. A quantitative biomarker-panel mini-array (BPMA) system was developed and the sensitivity, specificity, reproducibility, and stability of the were examined. The performance of BPMA in disease monitoring was validated with machine models using a …

Changes In Functional Connectivity Are Associated With Functional Independence In The Early Postoperative Period Following Awake Surgical Resection Of Language-Eloquent Glioma, Kyle R Noll, Evan D Bander, Henry S Chen, Mariana Bradshaw, Jeffrey S Wefel, Vinodh A Kumar, Sujit S Prabhu, Ho-Ling Liu

Faculty, Staff and Student Publications

Background: Neurocognitive decline in patients with primary brain tumors is associated with alterations in the functional connectome and reduced independence in daily living. This study explores postoperative connectomic changes associated with functional independence outcomes in patients with eloquent glioma, and how these associations differ from neurocognitive-connetcomic relationships.

Methods: Fifteen patients with left perisylvian glioma underwent resting-state functional magnetic resonance imaging (fMRI) and neuropsychological evaluation within 2 weeks before and on average 1 month after resection. Functional independence was measured with the Physical Self-Maintenance Scale (PSMS) and the Instrumental Activities of Daily Living scale (IADL). Graph theoretical analysis quantified functional brain …

Combining Biology-Based And Mri Data-Driven Modeling To Predict Response To Neoadjuvant Chemotherapy In Patients With Triple-Negative Breast Cancer, Casey E Stowers, Chengyue Wu, Zhan Xu, Sidharth Kumar, Clinton Yam, Jong Bum Son, Jingfei Ma, Jonathan I Tamir, Gaiane M Rauch, Thomas E Yankeelov

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with limited targeted treatment options, heterogeneous treatment response, and high risk of early recurrence. Artificial intelligence (AI) has rapidly emerged as a powerful tool to address key clinical challenges in TNBC across diagnosis, treatment response assessment, and prognosis. Diagnostic and staging challenges persist due to variable imaging features in TNBC and limitations in conventional modalities, increasing the risk of delayed detection. Predicting response to neoadjuvant systemic therapy remains difficult, as patient responses are heterogeneous, and existing clinical markers provide limited early predictive value. Prognostication in TNBC is similarly constrained …

A Cytotoxic Peptide-Drug Conjugate For Tumor-Specific Delivery Of Co-Injected Molecules, Norio Miyamura, Chisato M Yamazaki, Yasuaki Anami, Kyoji Tsuchikama, Kazuki N Sugahara

Faculty, Staff and Student Publications

An ideal cancer therapy enhances anti-tumor effects while minimizing side effects. iRGD, a non-cytotoxic peptide that activates a tumor-specific molecular transport machinery, promotes the penetration of co-injected drugs into tumor tissues. Clinical trials have demonstrated its potential as a tumor-specific delivery scaffold and potentiator of anti-cancer agents. In this study, we synthesized an iRGD conjugate containing monomethyl auristatin F (MMAF), a highly toxic antimitotic agent, and characterized its dual function as a tumor-specific cytotoxic agent and co-injected drug delivery scaffold. The iRGD-MMAF conjugate internalized and killed cultured tumor cells in an αv integrin-dependent manner. When injected systemically, iRGD-MMAF homed selectively …

Digital Otoscopy With Computer-Aided Composite Image Generation: Impact On The Correct Diagnosis, Confidence, And Time, Seda Camalan, Carl D Langefeld, Amy Zinnia, Brigham Mckee, Matthew L Carlson, Nicholas L Deep, Michael S Harris, Taha A Jan, Vivian F Kaul, Nathan R Lindquist, Jameson K Mattingly, Jay Shah, Kevin Y Zhan, Metin N Gurcan, Aaron C Moberly

Faculty, Staff and Student Publications

Objective: This study investigated the comparative performance of ear, nose, and throat (ENT) physicians in correctly detecting ear abnormalities when reviewing digital otoscopy imaging using 3 different visualization methods, including computer-assisted composite images called "SelectStitch," single video frame "Still" images, and video clips. The study also explored clinicians' diagnostic confidence levels and the time to make a diagnosis.

Study design: Clinician diagnostic reader study.

Setting: Online diagnostic survey of ENT physicians.

Methods: Nine ENT physicians reviewed digital otoscopy examinations from 86 ears with various diagnoses (normal, perforation, retraction, middle ear effusion, tympanosclerosis). Otoscopy examinations used artificial-intelligence (AI)-based computer-aided composite image …

Smoking Habit And Long-Term Colorectal Cancer Incidence By Exome-Wide Mutational And Neoantigen Loads: Evidence Based On The Prospective Cohort Incident-Tumour Biobank Method, Tsuyoshi Hamada, Tomotaka Ugai, Carino Gurjao, Satoko Ugai, Xuehong Zhang, Koichiro Haruki, Yasutoshi Takashima, Naohiko Akimoto, Mai Chan Lau, Kosuke Matsuda, Nobuhiro Nakazawa, Mayu Higashioka, Satoshi Miyahara, Keisuke Kosumi, Yohei Masugi, Li Liu, Yin Cao, Daniel Nevo, Molin Wang, Reiko Nishihara, Sachet A Shukla, Catherine J Wu, Levi A Garraway, Jeffrey A Meyerhardt, Edward L Giovannucci, Jonathan A Nowak, Charles S Fuchs, Andrew T Chan, Mingyang Song, Marios Giannakis, Shuji Ogino

Faculty, Staff and Student Publications

Objective: To test the hypothesis that the association of smoking with long-term colorectal cancer incidence may be stronger for tumours with higher mutational and neoantigen loads.

Methods and analysis: In the Nurses' Health Study (1980-2012) and the Health Professionals Follow-up Study (1986-2012), our novel prospective cohort incident-tumour biobank method (PCIBM) used 3053 incident colorectal carcinoma cases including 752 cases with whole-exome sequencing data. Using the multivariable duplication-method Cox regression model with the inverse probability weighting to adjust for the selection bias due to tissue availability, we assessed a differential association of cigarette smoking with colorectal carcinoma incidence by an exome-wide …

Integrating Multi-Omics Data To Uncover Prostate Tissue Dna Methylation Biomarkers And Target Genes For Prostate Cancer Risk, Shuai Liu, Jingjing Zhu, Dylan Green, Hua Zhong, Quan Long, Chong Wu, Liang Wang, Youping Deng, Lang Wu

Faculty, Staff and Student Publications

Previous studies have indicated that specific CpG sites may be linked to the risk of prostate cancer (PCa) by regulating the expression of PCa target genes. However, most existing studies aim to identify DNA methylation (DNAm) biomarkers through blood tissue genetic instruments, which impedes the identification of relevant biomarkers in prostate tissue. To identify PCa risk-associated CpG sites in prostate tissue, we established genetic prediction models of DNAm levels using data from normal prostate samples in the GTEx (N = 108) and assessed associations between genetically predicted DNAm in prostate and PCa risk by studying 122,188 cases and 604,640 controls. …

Integrative Multi-Omics Approach For Improving Causal Gene Identification, Austin King, Chong Wu

Faculty, Staff and Student Publications

Transcriptome-wide association studies (TWAS) have been widely used to identify thousands of likely causal genes for diseases and complex traits using predicted expression models. However, most existing TWAS methods rely on gene expression alone and overlook other regulatory mechanisms of gene expression, including DNA methylation and splicing, that contribute to the genetic basis of these complex traits and diseases. Here we introduce a multi-omics method that integrates gene expression, DNA methylation, and splicing data to improve the identification of associated genes with our traits of interest. Through simulations and by analyzing genome-wide association study (GWAS) summary statistics for 24 complex …