Medicine and Health Sciences Commons^™

Changes In Outcomes And Factors Associated With Survival In Melanoma Patients With Brain Metastases, Merve Hasanov, Denái R Milton, Alicia Bea Davies, Elizabeth Sirmans, Chantal Saberian, Eliza L Posada, Sylvia Opusunju, Jeffrey E Gershenwald, Carlos A Torres-Cabala, Elizabeth M Burton, Rivka R Colen, Jason T Huse, Isabella C Glitza Oliva, Caroline Chung, Mary Frances Mcaleer, Susan L Mcgovern, Debra N Yeboa, Betty Y S Kim, Sujit S Prabhu, Ian E Mccutcheon, Jeffrey S Weinberg, Frederick F Lang, Hussein A Tawbi, Jing Li, Lauren E Haydu, Michael A Davies, Sherise D Ferguson

Faculty, Staff and Student Publications

BACKGROUND: Treatment options for patients with melanoma brain metastasis (MBM) have changed significantly in the last decade. Few studies have evaluated changes in outcomes and factors associated with survival in MBM patients over time. The aim of this study is to evaluate changes in clinical features and overall survival (OS) for MBM patients.

METHODS: Patients diagnosed with MBMs from 1/1/2009 to 12/31/2013 (Prior Era; PE) and 1/1/2014 to 12/31/2018 (Current Era; CE) at The University of Texas MD Anderson Cancer Center were included in this retrospective analysis. The primary outcome measure was OS. Log-rank test assessed differences between groups; multivariable …

A Functional Link Between Lariat Debranching Enzyme And The Intron-Binding Complex Is Defective In Non-Photosensitive Trichothiodystrophy, Brittany A Townley, Luke Buerer, Ning Tsao, Albino Bacolla, Fadhel Mansoori, Timur Rusanov, Nathanial Clark, Negar Goodarzi, Nicolas Schmidt, Sridhar Nonavinkere Srivatsan, Hua Sun, Reilly A Sample, Joshua R Brickner, Drew Mcdonald, Miaw-Sheue Tsai, Matthew J Walter, David F Wozniak, Alex S Holehouse, Vladimir Pena, John A Tainer, William G Fairbrother, Nima Mosammaparast

Faculty, Staff and Student Publications

The pre-mRNA life cycle requires intron processing; yet, how intron-processing defects influence splicing and gene expression is unclear. Here, we find that TTDN1/MPLKIP, which is encoded by a gene implicated in non-photosensitive trichothiodystrophy (NP-TTD), functionally links intron lariat processing to spliceosomal function. The conserved TTDN1 C-terminal region directly binds lariat debranching enzyme DBR1, whereas its N-terminal intrinsically disordered region (IDR) binds the intron-binding complex (IBC). TTDN1 loss, or a mutated IDR, causes significant intron lariat accumulation, as well as splicing and gene expression defects, mirroring phenotypes observed in NP-TTD patient cells. A Ttdn1-deficient mouse model recapitulates intron-processing defects and certain …

Feasibility And Safety Of Personalized, Multi-Target, Adoptive Cell Therapy (Ima101): First-In-Human Clinical Trial In Patients With Advanced Metastatic Cancer, Apostolia M Tsimberidou, Kerstin Guenther, Borje S Andersson, Regina Mendrzyk, Amir Alpert, Claudia Wagner, Anna Nowak, Katrin Aslan, Arun Satelli, Fabian Richter, Sabrina Kuttruff-Coqui, Oliver Schoor, Jens Fritsche, Zoe Coughlin, Ali S Mohamed, Kerry Sieger, Becky Norris, Rita Ort, Jennifer Beck, Henry Hiep Vo, Franziska Hoffgaard, Manuel Ruh, Linus Backert, Ignacio I Wistuba, David Fuhrmann, Nuhad K Ibrahim, Van Karlyle Morris, Bryan K Kee, Daniel M Halperin, Graciela M Nogueras-Gonzalez, Partow Kebriaei, Elizabeth J Shpall, David Vining, Patrick Hwu, Harpreet Singh, Carsten Reinhardt, Cedrik M Britten, Norbert Hilf, Toni Weinschenk, Dominik Maurer, Steffen Walter

Faculty, Staff and Student Publications

IMA101 is an actively personalized, multi-targeted adoptive cell therapy (ACT), whereby autologous T cells are directed against multiple novel defined peptide-HLA (pHLA) cancer targets. HLA-A*02:01-positive patients with relapsed/refractory solid tumors expressing ≥1 of 8 predefined targets underwent leukapheresis. Endogenous T cells specific for up to 4 targets were primed and expanded in vitro. Patients received lymphodepletion (fludarabine, cyclophosphamide), followed by T-cell infusion and low-dose IL2 (Cohort 1). Patients in Cohort 2 received atezolizumab for up to 1 year (NCT02876510). Overall, 214 patients were screened, 15 received lymphodepletion (13 women, 2 men; median age, 44 years), and 14 were treated with …

Phase Ii Trial Of Medi0457 And Durvalumab For Patients With Recurrent/Metastatic Human Papillomavirus-Associated Cancers, Van K Morris, Amir Jazaeri, Shannon N Westin, Curtis Pettaway, Solly George, Ryan W Huey, Michaela Grinsfelder, Aaron Shafer, Benny Johnson, David Vining, Ming Guo, Bryan Fellman, Michael Frumovitz

Faculty, Staff and Student Publications

BACKGROUND: Human papillomavirus (HPV) types 16/18 drive oncogenesis for most patients with cervical, anal, and penile cancers. MEDI0457, a therapeutic DNA vaccine containing plasmids for E6 and E7 HPV-16/18 viral oncogenes and IL-12 adjuvant, is safe and provokes an immune response against E6/E7. We tested MEDI0457 with the anti-PD-L1 antibody durvalumab for patients with HPV-associated cancers.

METHODS: Patients with recurrent/metastatic, treatment-refractory HPV-16/18 cervical cancer, or rare HPV-associated (anal and penile) cancers were eligible. Prior immune checkpoint inhibition was not permitted. Patients received MEDI0457 7 mg intramuscularly (weeks 1, 3, 7, 12, and every 8 weeks thereafter) and durvalumab 1500 mg …

A Phase Ib/Ii Study Of Ivosidenib With Venetoclax ± Azacitidine In Idh1-Mutated Myeloid Malignancies, Curtis A Lachowiez, Sanam Loghavi, Zhihong Zeng, Tomoyuki Tanaka, Yi June Kim, Hidetaka Uryu, Sven Turkalj, Niels Asger Jakobsen, Marlise R Luskin, Dzifa Y Duose, Rebecca S S Tidwell, Nicholas J Short, Gautam Borthakur, Tapan M Kadia, Lucia Masarova, George D Tippett, Prithviraj Bose, Elias J Jabbour, Farhad Ravandi, Naval G Daver, Guillermo Garcia-Manero, Hagop Kantarjian, Jacqueline S Garcia, Paresh Vyas, Koichi Takahashi, Marina Konopleva, Courtney D Dinardo

Faculty, Staff and Student Publications

UNLABELLED: The safety and efficacy of combining the isocitrate dehydrogenase-1 (IDH1) inhibitor ivosidenib (IVO) with the BCL2 inhibitor venetoclax (VEN; IVO + VEN) ± azacitidine (AZA; IVO + VEN + AZA) were evaluated in four cohorts of patients with IDH1-mutated myeloid malignancies (n = 31). Most (91%) adverse events were grade 1 or 2. The maximal tolerated dose was not reached. Composite complete remission with IVO + VEN + AZA versus IVO + VEN was 90% versus 83%. Among measurable residual disease (MRD)-evaluable patients (N = 16), 63% attained MRD--negative remissions; IDH1 mutation clearance occurred in 64% of patients receiving …

Lgr4 And Lgr5 Form Distinct Homodimers That Only Lgr4 Complexes With Rnf43/Znrf3 To Provide High Affinity Binding Of R-Spondin Ligands, Yukimatsu Toh, Ling Wu, Soohyun Park, Allison Wang, Jianghua Tu, Wangsheng Yu, Mingxin Zuo, Kendra S Carmon, Qingyun J Liu

Faculty, Staff and Student Publications

LGR4 and LGR5 are two homologous receptors that potentiate Wnt/β-catenin signaling in response to R-spondin (RSPO) ligands. The RSPO and LGR4 complex binds to and inhibits activities of two related E3 ubiquitin ligases, RNF43 and ZNRF3, and thus protects Wnt receptors from the E3 ligase-mediated degradation. The RSPO and LGR5 complex, however, does not interact with the E3 ligases, and the structural basis of this difference remained unknown. Here we examined the affinities of monovalent and bivalent RSPO ligands in binding to LGR4, RNF43/ZNRF3, and LGR5 in whole cells and found unique features among the receptors and E3 ligases. Monovalent …

A Bayesian Network Approach To Social And Nonsocial Cognition In Schizophrenia: Are Some Domains More Fundamental Than Others?, Samuel J Abplanalp, Junghee Lee, William P Horan, Robert S Kern, David L Penn, Michael F Green

Faculty, Staff and Student Publications

OBJECTIVES: Social and nonsocial cognition are defined as distinct yet related constructs. However, the relative independence of individual variables-and whether specific tasks directly depend on performance in other tasks-is still unclear. The current study aimed to answer this question by using a Bayesian network approach to explore directional dependencies among social and nonsocial cognitive domains.

STUDY DESIGN: The study sample comprised 173 participants with schizophrenia (71.7% male; 28.3% female). Participants completed 5 social cognitive tasks and the MATRICS Consensus Cognitive Battery. We estimated Bayesian networks using directed acyclic graph structures to examine directional dependencies among the variables.

STUDY RESULTS: After …

Social And Environmental Determinants Influencing Injection Drug Use And Hiv Risk Among Two Sister Cities On The Us-Mexico Border: A Comparative Cross-Sectional Study, 2016–2018, Julia Lechuga, Rebeca Ramos, Natasha Ludwig-Barron, Gilberto Perez, Maria Elena Ramos, João B Ferreira-Pinto, Jacquelin I Cordero, John Sauceda, Jorge Salazar

Faculty, Staff and Student Publications

The economic, social, cultural and political milieus that influence injection drug-related HIV risk behaviors along the US-Mexico border in the previous decade have been studied comparing cities on an East-West axis. In an effort to inform interventions targeting factors beyond the individual level, we used a cross-sectional study design comparing people who inject drugs during 2016-2018, living on a North-South axis, in two cities-Ciudad Juárez, Chihuahua, Mexico and El Paso, Texas, USA-situated at the midpoint of the 2000 US-Mexico borderland stretch. We conceptualize injection drug use and its antecedents and consequences as influenced by factors operating at various levels of …

Risks Of Alcohol And Drug Use Disorders In Prostate Cancer Survivors: A National Cohort Study, Casey Crump, Pär Stattin, James D Brooks, Jan Sundquist, Alexis C Edwards, Weiva Sieh, Kristina Sundquist

Faculty, Staff and Student Publications

BACKGROUND: Prostate cancer (PC) survivors may potentially use substances to cope with psychological distress or poorly controlled physical symptoms. Little is known, however, about the long-term risks of alcohol use disorder (AUD) or drug use disorders in men with PC.

METHODS: A national cohort study was conducted in Sweden of 180 189 men diagnosed with PC between 1998 and 2017 and 1 801 890 age-matched population-based control men. AUD and drug use disorders were ascertained from nationwide records through 2018. Cox regression was used to compute hazard ratios (HRs) while adjusting for sociodemographic factors and prior psychiatric disorders. Subanalyses examined …

The Swi/Snf Chromatin-Remodeling Subunit Dpf2 Facilitates Nrf2-Dependent Antiinflammatory And Antioxidant Gene Expression, Gloria Mas, Na Man, Yuichiro Nakata, Concepcion Martinez-Caja, Daniel Karl, Felipe Beckedorff, Francesco Tamiro, Chuan Chen, Stephanie Duffort, Hidehiro Itonaga, Adnan K Mookhtiar, Kranthi Kunkalla, Alfredo M Valencia, Clayton K Collings, Cigall Kadoch, Francisco Vega, Scott C Kogan, Ramin Shiekhattar, Lluis Morey, Daniel Bilbao, Stephen D Nimer

Faculty, Staff and Student Publications

During emergency hematopoiesis, hematopoietic stem cells (HSCs) rapidly proliferate to produce myeloid and lymphoid effector cells, a response that is critical against infection or tissue injury. If unresolved, this process leads to sustained inflammation, which can cause life-threatening diseases and cancer. Here, we identify a role of double PHD fingers 2 (DPF2) in modulating inflammation. DPF2 is a defining subunit of the hematopoiesis-specific BAF (SWI/SNF) chromatin-remodeling complex, and it is mutated in multiple cancers and neurological disorders. We uncovered that hematopoiesis-specific Dpf2-KO mice developed leukopenia, severe anemia, and lethal systemic inflammation characterized by histiocytic and fibrotic tissue infiltration resembling a …

Reasons Patients Cite To Their Health-Care Professional For Not Initiating Or Completing Human Papillomavirus Vaccination, Onyema Greg Chido-Amajuoyi, Ikponmwosa Osaghae, Sanjay Shete

Faculty, Staff and Student Publications

BACKGROUND: Vaccination against human papillomavirus (HPV) is critical to the prevention of HPV-associated cancers. This study aimed to describe the reasons patients cited for not initiating or completing the HPV vaccination series, as reported by health-care professionals.

METHODS: Study data were obtained from a University of Texas MD Anderson Cancer Center population-based cross-sectional survey of health-care professionals practicing in Texas. Prevalence estimates of reasons cited for not initiating or completing HPV vaccination were estimated by patient population (parents of children and adult patients).

RESULTS: The study included 973 primary care clinicians, of whom 45.53% were physicians and 54.47% were midlevel …

Association Of Circulating Tumor Dna Testing Before Tissue Diagnosis With Time To Treatment Among Patients With Suspected Advanced Lung Cancer: The Accelerate Nonrandomized Clinical Trial, Miguel García-Pardo, Kasia Czarnecka-Kujawa, Jennifer H Law, Alexandra M Salvarrey, Roxanne Fernandes, Zhen J Fan, Thomas K Waddell, Kazuhiro Yasufuku, Geoffrey Liu, Laura L Donahoe, Andrew Pierre, Lisa W Le, Tharsiga Gunasegaran, Noor Ghumman, Frances A Shepherd, Penelope A Bradbury, Adrian G Sacher, Sabine Schmid, Lucy Corke, Jamie Feng, Tracy Stockley, Prodipto Pal, Patrik Rogalla, Christodoulos Pipinikas, Karen Howarth, Bana Ambasager, Laura Mezquita, Ming S Tsao, Natasha B Leighl

Faculty, Staff and Student Publications

IMPORTANCE: Liquid biopsy has emerged as a complement to tumor tissue profiling for advanced non-small cell lung cancer (NSCLC). The optimal way to integrate liquid biopsy into the diagnostic algorithm for patients with newly diagnosed advanced NSCLC remains unclear.

OBJECTIVE: To evaluate the use of circulating tumor DNA (ctDNA) genotyping before tissue diagnosis among patients with suspected advanced NSCLC and its association with time to treatment.

DESIGN, SETTING, AND PARTICIPANTS: This single-group nonrandomized clinical trial was conducted among 150 patients at the Princess Margaret Cancer Centre-University Health Network (Toronto, Ontario, Canada) between July 1, 2021, and November 30, 2022. Patients …

The Hipaa Privacy Rule At Age 25: Privacy For Equitable Ai, Barbara J. Evans

UF Law Faculty Publications

This Article argues that unconsented access to data is not ethically problematic in and of itself. What has made it problematic is the weak framework of alternative protections that the Privacy Rule prescribes when data are used without individual consent. This Article proposes specific measures to strengthen those protections so that the pursuit of greater health care equity need not imply a loss of meaningful privacy standards.

Part I describes two competing visions of how to protect data privacy, examining the roots of ongoing discontent with the Privacy Rule and tracing policymakers’ original rationale for fashioning a major federal privacy …

Fast Inference Of Genetic Recombination Rates In Biobank Scale Data, Ardalan Naseri, William Yue, Shaojie Zhang, Degui Zhi

Faculty, Staff and Student Publications

Although rates of recombination events across the genome (genetic maps) are fundamental to genetic research, the majority of current studies only use one standard map. There is evidence suggesting population differences in genetic maps, and thus estimating population-specific maps, are of interest. Although the recent availability of biobank-scale data offers such opportunities, current methods are not efficient at leveraging very large sample sizes. The most accurate methods are still linkage disequilibrium (LD)-based methods that are only tractable for a few hundred samples. In this work, we propose a fast and memory-efficient method for estimating genetic maps from population genotyping data. …

Associations Between Kir/Kir-Ligand Genotypes And Clinical Outcome For Patients With Advanced Solid Tumors Receiving Bempeg Plus Nivolumab Combination Therapy In The Pivot-02 Trial, A S Feils, A K Erbe, J Birstler, K Kim, U Hoch, S L Currie, T Nguyen, D Yu, A O Siefker-Radtke, N Tannir, S M Tolaney, A Diab, P M Sondel

Faculty, Staff and Student Publications

Bempegaldesleukin (BEMPEG), a CD122-preferential IL2 pathway agonist, has been shown to induce proliferation and activation of NK cells. NK activation is dependent on the balance of inhibitory and excitatory signals transmitted by NK receptors, including Fc-gamma receptors (FCγRs) and killer immunoglobulin-like receptors (KIRs) along with their KIR-ligands. The repertoire of KIRs/KIR-ligands an individual inherits and the single-nucleotide polymorphisms (SNPs) of FCγRs can influence NK function and affect responses to immunotherapies. In this retrospective analysis of the single-arm PIVOT-02 trial, 200 patients with advanced solid tumors were genotyped for KIR/KIR-ligand gene status and FCγR SNP status and evaluated for associations with …

Dna Methylation-Based Classifier Differentiates Intrahepatic Pancreato-Biliary Tumours, Mihnea P Dragomir, Teodor G Calina, Eilís Perez, Simon Schallenberg, Meng Chen, Thomas Albrecht, Ines Koch, Peggy Wolkenstein, Benjamin Goeppert, Stephanie Roessler, George A Calin, Christine Sers, David Horst, Florian Roßner, David Capper

Faculty, Staff and Student Publications

BACKGROUND: Differentiating intrahepatic cholangiocarcinomas (iCCA) from hepatic metastases of pancreatic ductal adenocarcinoma (PAAD) is challenging. Both tumours have similar morphological and immunohistochemical pattern and share multiple driver mutations. We hypothesised that DNA methylation-based machine-learning algorithms may help perform this task.

METHODS: We assembled genome-wide DNA methylation data for iCCA (n = 259), PAAD (n = 431), and normal bile duct (n = 70) from publicly available sources. We split this cohort into a reference (n = 399) and a validation set (n = 361). Using the reference cohort, we trained three machine learning models to differentiate between these entities. Furthermore, …

Multi-Task Learning With Dynamic Re-Weighting To Achieve Fairness In Healthcare Predictive Modeling, Can Li, Sirui Ding, Na Zou, Xia Hu, Xiaoqian Jiang, Kai Zhang

Faculty, Staff and Student Publications

The emphasis on fairness in predictive healthcare modeling has increased in popularity as an approach for overcoming biases in automated decision-making systems. The aim is to guarantee that sensitive characteristics like gender, race, and ethnicity do not influence prediction outputs. Numerous algorithmic strategies have been proposed to reduce bias in prediction results, mitigate prejudice toward minority groups and promote prediction fairness. The goal of these strategies is to ensure that model prediction performance does not exhibit significant disparity among sensitive groups. In this study, we propose a novel fairness-achieving scheme based on multitask learning, which fundamentally differs from conventional fairness-achieving …

Radiomic And Deep Learning Characterization Of Breast Parenchyma On Full Field Digital Mammograms And Specimen Radiographs: A Pilot Study Of A Potential Cancer Field Effect, Natalie Baughan, Hui Li, Li Lan, Matthew Embury, Isaiah Yim, Gary J Whitman, Randa El-Zein, Isabelle Bedrosian, Maryellen L Giger

Faculty, Staff and Student Publications

PURPOSE: In women with biopsy-proven breast cancer, histologically normal areas of the parenchyma have shown molecular similarity to the tumor, supporting a potential cancer field effect. The purpose of this work was to investigate relationships of human-engineered radiomic and deep learning features between regions across the breast in mammographic parenchymal patterns and specimen radiographs.

APPROACH: This study included mammograms from 74 patients with at least 1 identified malignant tumor, of whom 32 also possessed intraoperative radiographs of mastectomy specimens. Mammograms were acquired with a Hologic system and specimen radiographs were acquired with a Fujifilm imaging system. All images were retrospectively …

Effects Of A School-Based Gardening, Cooking, And Nutrition Cluster Randomized Controlled Trial On Unprocessed And Ultra-Processed Food Consumption, Matthew R Jeans, Matthew J Landry, Sarvenaz Vandyousefi, Erin A Hudson, Marissa Burgermaster, Molly S Bray, Joya Chandra, Jaimie N Davis

Faculty, Staff and Student Publications

BACKGROUND: School-based gardening and nutrition education interventions report improvements in dietary intake, notably through fruit and vegetables. However, gardening, cooking, and nutrition randomized controlled trials are limited in evaluating dietary quality, and none have examined processed food consumption to date.

OBJECTIVES: The study examined the effects of Texas Sprouts (TX Sprouts), a gardening, cooking, and nutrition education intervention, compared with control on unprocessed and ultra-processed food (UPF) consumption in predominately low-income Hispanic children.

METHODS: TX Sprouts was a school-based cluster randomized controlled trial that consisted of 16 elementary schools randomly assigned to either the TX Sprouts intervention (n = 8 …

Who, Where, When: Colorectal Cancer Disparities By Race And Ethnicity, Subsite, And Stage, Kristin M Primm, Andrea Joyce Malabay, Taylor Curry, Shine Chang

Faculty, Staff and Student Publications

BACKGROUND: There are well-established disparities in colorectal cancer (CRC) outcomes between White and Black patients; however, assessments of CRC disparities for other racial/ethnic groups are limited.

METHODS: The Surveillance, Epidemiology, and End Results database identified patients aged 50-74 years with CRC adenocarcinoma from 2000 to 2019. Trends in age-adjusted incidence rates were computed by stage at diagnosis and subsite across five broad race/ethnic groups (White, Black, Asian/Pacific Islander [API], American Indian/Alaskan Native [AIAN], and Hispanic) and four API subgroups (East Asian, Southeast Asian, South Asian, and Pacific Islander) Multivariable logistic regression evaluated associations between race/ethnicity and diagnosis stage. Multivariable Cox …

Weakly Supervised Spatial Relation Extraction From Radiology Reports, Surabhi Datta, Kirk Roberts

Faculty, Staff and Student Publications

OBJECTIVE: Weak supervision holds significant promise to improve clinical natural language processing by leveraging domain resources and expertise instead of large manually annotated datasets alone. Here, our objective is to evaluate a weak supervision approach to extract spatial information from radiology reports.

MATERIALS AND METHODS: Our weak supervision approach is based on data programming that uses rules (or labeling functions) relying on domain-specific dictionaries and radiology language characteristics to generate weak labels. The labels correspond to different spatial relations that are critical to understanding radiology reports. These weak labels are then used to fine-tune a pretrained Bidirectional Encoder Representations from …

Effect Of Longitudinal Variation In Tumor Volume Estimation For Mri-Guided Personalization Of Breast Cancer Neoadjuvant Treatment, Natsuko Onishi, Teffany Joy Bareng, Jessica Gibbs, Wen Li, Elissa R Price, Bonnie N Joe, John Kornak, Laura J Esserman, David C Newitt, Nola M Hylton, I-Spy 2 Investigator Network

Faculty, Staff and Student Publications

Purpose To investigate the impact of longitudinal variation in functional tumor volume (FTV) underestimation and overestimation in predicting pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC). Materials and Methods Women with breast cancer who were enrolled in the prospective I-SPY 2 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis 2) from May 2010 to November 2016 were eligible for this retrospective analysis. Participants underwent four MRI examinations during NAC treatment. FTV was calculated based on automated segmentation. Baseline FTV before treatment (FTV0) and the percentage of FTV change at early treatment and inter-regimen …

Minimal Positional Substring Cover Is A Haplotype Threading Alternative To Li And Stephens Model, Ahsan Sanaullah, Degui Zhi, Shaojie Zhang

Faculty, Staff and Student Publications

The Li and Stephens (LS) hidden Markov model (HMM) models the process of reconstructing a haplotype as a mosaic copy of haplotypes in a reference panel. For small panels, the probabilistic parameterization of LS enables modeling the uncertainties of such mosaics. However, LS becomes inefficient when sample size is large, because of its linear time complexity. Recently the PBWT, an efficient data structure capturing the local haplotype matching among haplotypes, was proposed to offer a fast method for giving some optimal solution (Viterbi) to the LS HMM. Previously, we introduced the minimal positional substring cover (MPSC) problem as an alternative …

Histone Demethylase Kdm5d Upregulation Drives Sex Differences In Colon Cancer, Jiexi Li, Zhengdao Lan, Wenting Liao, James W Horner, Xueping Xu, Jielin Liu, Yohei Yoshihama, Shan Jiang, Hong Seok Shim, Max Slotnik, Kyle A Labella, Chang-Jiun Wu, Kenneth Dunner, Wen-Hao Hsu, Rumi Lee, Isha Khanduri, Christopher Terranova, Kadir Akdemir, Deepavali Chakravarti, Xiaoying Shang, Denise J Spring, Y Alan Wang, Ronald A Depinho

Faculty, Staff and Student Publications

Sex exerts a profound impact on cancer incidence, spectrum and outcomes, yet the molecular and genetic bases of such sex differences are ill-defined and presumptively ascribed to X-chromosome genes and sex hormones1. Such sex differences are particularly prominent in colorectal cancer (CRC) in which men experience higher metastases and mortality. A murine CRC model, engineered with an inducible transgene encoding oncogenic mutant KRASG12D and conditional null alleles of Apc and Trp53 tumour suppressors (designated iKAP)2, revealed higher metastases and worse outcomes specifically in males with oncogenic mutant KRAS (KRAS*) CRC. Integrated cross-species molecular and transcriptomic analyses identified Y-chromosome gene histone …

Imaging In Interventional Radiology: 2043 And Beyond, Kristy K Brock, Stephen R Chen, Rahul A Sheth, Jeffrey H Siewerdsen

Faculty, Staff and Student Publications

Since its inception in the early 20th century, interventional radiology (IR) has evolved tremendously and is now a distinct clinical discipline with its own training pathway. The arsenal of modalities at work in IR includes x-ray radiography and fluoroscopy, CT, MRI, US, and molecular and multimodality imaging within hybrid interventional environments. This article briefly reviews the major developments in imaging technology in IR over the past century, summarizes technologies now representative of the standard of care, and reflects on emerging advances in imaging technology that could shape the field in the century ahead. The role of emergent imaging technologies in …

Genome-Wide Association Study Of Bladder Cancer Reveals New Biological And Translational Insights, Stella Koutros, Lambertus A Kiemeney, Parichoy Pal Choudhury, Roger L Milne, Evangelina Lopez De Maturana, Yuanqing Ye, Vijai Joseph, Oscar Florez-Vargas, Lars Dyrskjøt, Jonine Figueroa, Diptavo Dutta, Graham G Giles, Michelle A T Hildebrandt, Kenneth Offit, Manolis Kogevinas, Elisabete Weiderpass, Marjorie L Mccullough, Neal D Freedman, Demetrius Albanes, Charles Kooperberg, Victoria K Cortessis, Margaret R Karagas, Alison Johnson, Molly R Schwenn, Dalsu Baris, Helena Furberg, Dean F Bajorin, Olivier Cussenot, Geraldine Cancel-Tassin, Simone Benhamou, Peter Kraft, Stefano Porru, Angela Carta, Timothy Bishop, Melissa C Southey, Giuseppe Matullo, Tony Fletcher, Rajiv Kumar, Jack A Taylor, Philippe Lamy, Frederik Prip, Mark Kalisz, Stephanie J Weinstein, Jan G Hengstler, Silvia Selinski, Mark Harland, Mark Teo, Anne E Kiltie, Adonina Tardón, Consol Serra, Alfredo Carrato, Reina García-Closas, Josep Lloreta, Alan Schned, Petra Lenz, Elio Riboli, Paul Brennan, Anne Tjønneland, Thomas Otto, Daniel Ovsiannikov, Frank Volkert, Sita H Vermeulen, Katja K Aben, Tessel E Galesloot, Constance Turman, Immaculata De Vivo, Edward Giovannucci, David J Hunter, Chancellor Hohensee, Rebecca Hunt, Alpa V Patel, Wen-Yi Huang, Gudmar Thorleifsson, Manuela Gago-Dominguez, Pilar Amiano, Klaus Golka, Mariana C Stern, Wusheng Yan, Jia Liu, Shengchao Alfred Li, Shilpa Katta, Amy Hutchinson, Belynda Hicks, William A Wheeler, Mark P Purdue, Katherine A Mcglynn, Cari M Kitahara, Christopher A Haiman, Mark H Greene, Thorunn Rafnar, Nilanjan Chatterjee, Stephen J Chanock, Xifeng Wu, Francisco X Real, Debra T Silverman, Montserrat Garcia-Closas, Kari Stefansson, Ludmila Prokunina-Olsson, Núria Malats, Nathaniel Rothman

Faculty, Staff and Student Publications

BACKGROUND: Genomic regions identified by genome-wide association studies (GWAS) for bladder cancer risk provide new insights into etiology.

OBJECTIVE: To identify new susceptibility variants for bladder cancer in a meta-analysis of new and existing genome-wide genotype data.

DESIGN, SETTING, AND PARTICIPANTS: Data from 32 studies that includes 13,790 bladder cancer cases and 343,502 controls of European ancestry were used for meta-analysis.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: Log-additive associations of genetic variants were assessed using logistic regression models. A fixed-effects model was used for meta-analysis of the results. Stratified analyses were conducted to evaluate effect modification by sex and smoking status. …

Evidence Of Novel Susceptibility Variants For Prostate Cancer And A Multiancestry Polygenic Risk Score Associated With Aggressive Disease In Men Of African Ancestry, Fei Chen, Ravi K Madduri, Alex A Rodriguez, Burcu F Darst, Alisha Chou, Xin Sheng, Anqi Wang, Jiayi Shen, Edward J Saunders, Suhn K Rhie, Jeannette T Bensen, Sue A Ingles, Rick A Kittles, Sara S Strom, Benjamin A Rybicki, Barbara Nemesure, William B Isaacs, Janet L Stanford, Wei Zheng, Maureen Sanderson, Esther M John, Jong Y Park, Jianfeng Xu, Ying Wang, Sonja I Berndt, Chad D Huff, Edward D Yeboah, Yao Tettey, Joseph Lachance, Wei Tang, Christopher T Rentsch, Kelly Cho, Benjamin H Mcmahon, Richard B Biritwum, Andrew A Adjei, Evelyn Tay, Ann Truelove, Shelley Niwa, Thomas A Sellers, Kosj Yamoah, Adam B Murphy, Dana C Crawford, Alpa V Patel, William S Bush, Melinda C Aldrich, Olivier Cussenot, Gyorgy Petrovics, Jennifer Cullen, Christine M Neslund-Dudas, Mariana C Stern, Zsofia Kote-Jarai, Koveela Govindasami, Michael B Cook, Anand P Chokkalingam, Ann W Hsing, Phyllis J Goodman, Thomas J Hoffmann, Bettina F Drake, Jennifer J Hu, Jacob M Keaton, Jacklyn N Hellwege, Peter E Clark, Mohamed Jalloh, Serigne M Gueye, Lamine Niang, Olufemi Ogunbiyi, Michael O Idowu, Olufemi Popoola, Akindele O Adebiyi, Oseremen I Aisuodionoe-Shadrach, Hafees O Ajibola, Mustapha A Jamda, Olabode P Oluwole, Maxwell Nwegbu, Ben Adusei, Sunny Mante, Afua Darkwa-Abrahams, James E Mensah, Halimatou Diop, Stephen K Van Den Eeden, Pascal Blanchet, Jay H Fowke, Graham Casey, Anselm J Hennis, Alexander Lubwama, Ian M Thompson, Robin Leach, Douglas F Easton, Michael H Preuss, Ruth J Loos, Susan M Gundell, Peggy Wan, James L Mohler, Elizabeth T Fontham, Gary J Smith, Jack A Taylor, Shiv Srivastava, Rosaline A Eeles, John D Carpten, Adam S Kibel, Luc Multigner, Marie-Élise Parent, Florence Menegaux, Geraldine Cancel-Tassin, Eric A Klein, Caroline Andrews, Timothy R Rebbeck, Laurent Brureau, Stefan Ambs, Todd L Edwards, Stephen Watya, Stephen J Chanock, John S Witte, William J Blot, J Michael Gaziano, Amy C Justice, David V Conti, Christopher A Haiman

Faculty, Staff and Student Publications

BACKGROUND: Genetic factors play an important role in prostate cancer (PCa) susceptibility.

OBJECTIVE: To discover common genetic variants contributing to the risk of PCa in men of African ancestry.

DESIGN, SETTING, AND PARTICIPANTS: We conducted a meta-analysis of ten genome-wide association studies consisting of 19378 cases and 61620 controls of African ancestry.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Common genotyped and imputed variants were tested for their association with PCa risk. Novel susceptibility loci were identified and incorporated into a multiancestry polygenic risk score (PRS). The PRS was evaluated for associations with PCa risk and disease aggressiveness.

RESULTS AND LIMITATIONS: Nine …

A Radiomics Model Based On Synthetic Mri Acquisition For Predicting Neoadjuvant Systemic Treatment Response In Triple-Negative Breast Cancer, Ken-Pin Hwang, Nabil A Elshafeey, Aikaterini Kotrotsou, Huiqin Chen, Jong Bum Son, Medine Boge, Rania M Mohamed, Abeer H Abdelhafez, Beatriz E Adrada, Bikash Panthi, Jia Sun, Benjamin C Musall, Shu Zhang, Rosalind P Candelaria, Jason B White, Elizabeth E Ravenberg, Debu Tripathy, Clinton Yam, Jennifer K Litton, Lei Huo, Alastair M Thompson, Peng Wei, Wei T Yang, Mark D Pagel, Jingfei Ma, Gaiane M Rauch

Faculty, Staff and Student Publications

Purpose

To determine if a radiomics model based on quantitative maps acquired with synthetic MRI (SyMRI) is useful for predicting neoadjuvant systemic therapy (NAST) response in triple-negative breast cancer (TNBC).

Materials and Methods

In this prospective study, 181 women diagnosed with stage I–III TNBC were scanned with a SyMRI sequence at baseline and at midtreatment (after four cycles of NAST), producing T1, T2, and proton density (PD) maps. Histopathologic analysis at surgery was used to determine pathologic complete response (pCR) or non-pCR status. From three-dimensional tumor contours drawn on the three maps, 310 histogram and textural features were extracted, resulting …

Pontocerebellar Hypoplasia Associated With Parg183trp Homozygous Variant In Exosc1 Gene: A Case Report, Nadirah S Damseh, Ali N Obeidat, Khondakar Sayef Ahammed, Motee Al-Ashhab, Motee Abu Awad, Ambro Van Hoof

Faculty, Staff and Student Publications

Pontocerebellar hypoplasia (PCH) is a heterogeneous group of rare neurodegenerative disorders characterized by a wide phenotypic range including severe motor and cognitive impairments, microcephaly, distinctive facial features, and other features according to the type. Several classes of PCH1 have been linked to mutations in the evolutionarily conserved RNA exosome complex that consists of nine subunits (EXOSC1 to EXOSC9) and facilitates the degradation and processing of cytoplasmic and nuclear RNA from the 3' end. Only a single individual with an EXOSC1 mutation was reported with clinical features of PCH type 1 (PCH1F). Here, we report a 3-month-old female with PCH and …

The Clinicogenomic Landscape Of Induction Failure In Childhood And Young Adult T-Cell Acute Lymphoblastic Leukemia, David O'Connor, Jonas Demeulemeester, Lucia Conde, Amy Kirkwood, Kent Fung, Foteini Papaleonidopoulou, Gianna Bloye, Nadine Farah, Sunniyat Rahman, Jeremy Hancock, Caroline Bateman, Sarah Inglott, Jon Mee, Javier Herrero, Peter Van Loo, Anthony V Moorman, Ajay Vora, Marc R Mansour

Faculty, Staff and Student Publications

PURPOSE: Failure to respond to induction chemotherapy portends a poor outcome in childhood acute lymphoblastic leukemia (ALL) and is more frequent in T-cell ALL (T-ALL) than B-cell ALL. We aimed to address the limited understanding of clinical and genetic factors that influence outcome in a cohort of patients with T-ALL induction failure (IF).

METHODS: We studied all cases of T-ALL IF on two consecutive multinational randomized trials, UKALL2003 and UKALL2011, to define risk factors, treatment, and outcomes. We performed multiomic profiling to characterize the genomic landscape.

RESULTS: IF occurred in 10.3% of cases and was significantly associated with increasing age, …