Medical Genetics Commons^™

Glucose Uptake In Pigment Glia Suppresses Tau-Induced Inflammation And Photoreceptor Degeneration, Mikiko Oka, Sho Nakajima, Emiko Suzuki, Shinya Yamamoto, Kanae Ando

Duncan NRI Faculty and Staff Publications

Brain inflammation contributes to the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD). Glucose hypometabolism and glial activation are pathological features seen in AD brains; however, the connection between the two is not fully understood. Using a Drosophila model of AD, we identified that glucose metabolism in glia plays a critical role in neuroinflammation under disease conditions. Expression of human MATP (hereafter referred to as Tau) in the retinal cells, including photoreceptor neurons and pigment glia, causes photoreceptor degeneration accompanied by the formation of dark-stained round inclusion-like structures and swelling of the lamina cortex. We found that inclusion-like structures …

De Novo Variants In Rybp Are Associated With A Severe Neurodevelopmental Disorder And Congenital Anomalies, Monika Weisz-Hubshman, Lindsay C Burrage, Sharayu V Jangam, Jill A Rosenfeld, Sandra Von Hardenberg, Anke Bergmann, Manuela Friederike Richter, Malgorzata Rydzanicz, Rafal Ploski, Agnieszka Stembalska, Wendy K Chung, Rebecca R Hernan, Foong Y Lim, Theresa Brunet, Steffen Syrbe, Boris Keren, Solveig Heide, David R Murdock, Hongzheng Dai, Fan Xia, Shamika Ketkar, Brian Dawson, Vinodh Narayanan, Hillary K Graves, Undiagnosed Diseases Network, Michael F Wangler, Carlos Bacino, Brendan Lee

Duncan NRI Faculty and Staff Publications

Purpose: Polycomb group proteins are key epigenetic transcriptional regulators. Multiple neurodevelopmental disorders are associated with pathogenic variants of the genes encoding Polycomb group proteins. RYBP is a core component of the noncanonical Polycomb Repressor Complex 1; however, its role in disease is unclear.

Methods: Functional consequences of RYBP variants were assessed using in vitro cellular and in vivo Drosophila melanogaster studies.

Results: We described 7 individuals with heterozygous de novo variants of RYBP and their clinical findings, including severe developmental delay, dysmorphisms, and multiple congenital anomalies. We showed that all single-nucleotide variants in RYBP localize to the N-terminal domain of …

Daratumumab/Lenalidomide/Dexamethasone In Transplant-Ineligible Newly Diagnosed Myeloma: Maia Long-Term Outcomes, Thierry Facon, Philippe Moreau, Katja Weisel, Hartmut Goldschmidt, Saad Z Usmani, Torben Plesner, Nizar Bahlis, Supratik Basu, Cyrille Hulin, Hang Quach, Michael O'Dwyer, Aurore Perrot, Caroline Jacquet, Christopher P Venner, Noopur Raje, Mourad Tiab, Margaret Macro, Laurent Frenzel, Xavier Leleu, Gordon Cook, George Wang, Huiling Pei, Maria Krevvata, Robin Carson, Fredrik Borgsten, Shaji K Kumar

Faculty, Staff and Student Publications

In the MAIA study, daratumumab plus lenalidomide and dexamethasone (D-Rd) improved progression-free survival (PFS) and overall survival (OS) versus lenalidomide and dexamethasone (Rd) alone in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). We report updated efficacy and safety from MAIA (median follow-up, 64.5 months), including a subgroup analysis by patient age (< 70, ≥70 to < 75, ≥75, and ≥80 years). Overall, 737 transplant-ineligible patients with NDMM were randomized 1:1 to D-Rd or Rd. The primary endpoint, PFS, was improved with D-Rd versus Rd (median, 61.9 vs 34.4 months; hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.45-0.67; P <  0.0001). Median OS was not reached in the D-Rd group versus 65.5 months in the Rd group (HR, 0.66; 95% CI, 0.53-0.83; P = 0.0003); estimated 60-month OS rates were 66.6% and 53.6%, respectively. D-Rd achieved higher rates of complete response or better (≥CR; 51.1% vs 30.1%), minimal residual disease (MRD) negativity (32.1% vs 11.1%), and sustained MRD negativity (≥18 months: 16.8% vs 3.3%) versus Rd (all P <  0.0001). D-Rd demonstrated clinically meaningful efficacy benefits across age groups. No new safety concerns were observed. Updated results (median follow-up, >5 years) continue to support frontline use of D-Rd in transplant-ineligible patients with NDMM.

Characterization Of A Time-Resolved, Real-Time Scintillation Dosimetry System For Ultra-High Dose-Rate Radiation Therapy Applications, Alexander Baikalov, Daline Tho, Kevin Liu, Stefan Bartzsch, Sam Beddar

Faculty, Staff and Student Publications

Purpose: Scintillation dosimetry has promising qualities for ultra-high-dose-rate (UHDR) radiation therapy (RT), but no system has shown compatibility with mean dose rates (DR¯) above 100 Gy/s and doses per pulse (Dp) exceeding 1.5 Gy typical of UHDR (FLASH)-RT. The aim of this study was to characterize a novel scintillation dosimetry system with the potential of accommodating UHDRs.

Methods and materials: We undertook a thorough dosimetric characterization of the system on an UHDR electron beamline. The system's response as a function of dose, DR¯, Dp, and the pulse dose-rate (DRp) was investigated, as was the system's dose sensitivity (signal per unit …

Diet And Survival After A Diagnosis Of Ovarian Cancer: A Pooled Analysis From The Ovarian Cancer Association Consortium, Christina M Nagle, Torukiri I Ibiebele, Renhua Na, Elisa V Bandera, Daniel Cramer, Graham G Giles, Gillian E Hanley, Holly R Harris, Allan Jensen, Susanne K Kjaer, Alice Lee, Valerie Mcguire, Roger L Milne, Bo Qin, Jean Richardson, Naoko Sasamoto, Joellen M Schildkraut, Weiva Sieh, Kathryn L Terry, Linda Titus, Britton Trabert, Nicolas Wentzensen, Anna H Wu, Andrew Berchuck, Malcolm C Pike, Celeste Leigh Pearce, Penelope M Webb, Multidisciplinary Ovarian Cancer Outcomes Group And Ovarian Cancer Association Consortium

Faculty, Staff and Student Publications

Background: Prognosis after a diagnosis of invasive epithelial ovarian cancer is poor. Some studies have suggested modifiable behaviors, like diet, are associated with survival but the evidence is inconsistent.

Objectives: This study aims to pool data from studies conducted around the world to evaluate the relationships among dietary indices, foods, and nutrients from food sources and survival after a diagnosis of ovarian cancer.

Methods: This analysis from the Multidisciplinary Ovarian Cancer Outcomes Group within the Ovarian Cancer Association Consortium included 13 studies with 7700 individuals with ovarian cancer, who completed food-frequency questionnaires regarding their prediagnosis diet. Adjusted hazard ratios (aHRs) …

External Validation Of An Algorithm To Detect Vertebral Level Mislabeling And Autocontouring Errors, Tucker J Netherton, Didier Duprez, Tina Patel, Gizem Cifter, Laurence E Court, Ajay Aggarwal

Faculty, Staff and Student Publications

Background and purpose: This work performs external validation of a previously developed vertebral body autocontouring tool and investigates a post-processing method to increase performance to clinically acceptable levels.

Materials and methods: Vertebral bodies within CT scans from two separate institutions (40 from institution A and 41 from institution B) were automatically 1) localized and enumerated, 2) contoured, and 3) screened as a means of quality assurance (QA) for errors. Identification rate, contour acceptability rate, and QA accuracy were calculated to assess the tool's performance. These metrics were compared to those calculated on CTs from the model's original training dataset, and …

Evaluation Of A Comprehensive Set Of Normal Tissue Complication Probability Models For Patients With Head And Neck Cancer In An International Cohort, Suzanne P M De Vette, Maria I Van Rijn-Dekker, Lisa Van Den Bosch, Kylie Keijzer, Hendrike Neh, Yan Li, Hans Paul Van Der Laan, Jolien Heukelom, Peter Van Luijk, Arjen Van Der Schaaf, Roel J H M Steenbakkers, Nanna M Sijtsema, Katherine A Hutcheson, Clifton D Fuller, Johannes A Langendijk, Amy C Moreno, Lisanne V Van Dijk

Faculty, Staff and Student Publications

Background/purpose: Normal tissue complication probability (NTCP) models can be used to guide radiation therapy (RT) decisions by estimating side-effect risks pretreatment to minimize (late) side-effects. Recently, a comprehensive individual toxicity risk (CITOR) profile of NTCP models addressing common side-effects in head and neck cancer (HNC) patients was developed. This study investigates the generalizability of these models in an international setting, with different treatment approaches and side-effect assessments, promoting their integration into more widespread clinical practice.

Materials/methods: From a prospective registry study, 407 HNC patients were included who were treated with definitive RT with or without systemic therapy between 2015 and …

A New Cure Model Accounting For Longitudinal Data And Flexible Patterns Of Hazard Ratios Over Time, Can Xie, Xuelin Huang, Ruosha Li, Yu Shen, Nicholas J Short

Faculty, Staff and Student Publications

With the advancement of medical treatments, many historically incurable diseases have become curable. An accurate estimation of the cure rates is of great interest. When there are no clear biomarker indicators for cure, the estimation of cure rate is intertwined with and influenced by the specification of hazard functions for uncured patients. Consequently, the commonly used proportional hazards (PH) assumption, when violated, may lead to biased cure rate estimation. Meanwhile, longitudinal biomarker measurements for individual patients are usually available. To accommodate non-PH functions and incorporate individual longitudinal biomarker trajectories, we propose a new joint model for cure, survival, and longitudinal …

Cytokine Storms In Covid-19, Hemophagocytic Lymphohistiocytosis, And Car-T Therapy, James P Long, Rishab Prakash, Paul Edelkamp, Mark Knafl, Anath C Lionel, Sairah Ahmed, Luis E Malpica Castillo, Ajlan Al-Zaki, Kelly Chien, Dai Chihara, Jason Westin, Fareed Khawaja, Loretta J Nastoupil, Victor Mulanovich, Andrew Futreal, Scott E Woodman, Naval G Daver, Christopher R Flowers, Sattva Neelapu, Joanna-Grace Manzano, Swaminathan P Iyer

Faculty, Staff and Student Publications

Importance: Cytokine storm (CS) is a hyperinflammatory syndrome causing multiorgan dysfunction and high mortality, especially in patients with malignant hematologic neoplasms. Triggers include malignant neoplasm-associated hemophagocytic lymphohistiocytosis (MN-HLH), cytokine release syndrome from chimeric antigen receptor T-cell therapy (CAR-T CRS), and COVID-19, but the underlying mechanisms of inflammation and their impact on outcomes are poorly understood.

Objective: To delineate the inflammatory patterns characterizing different CS etiologies and their association with clinical outcomes.

Design, setting, and participants: This retrospective cohort study was conducted at the MD Anderson Cancer Center in Houston, Texas, between March 1, 2020, and November 20, 2022, using the …

Cytotoxic And Regulatory T Cell Interactions Calculated From Image Mass Cytometry Predict Immunochemotherapy Response In Triple-Negative Breast Cancer, Xiang Wang, Jing Dong, Jian-Rong Li, Yupei Lin, Bikram Sahoo, Yanhong Liu, Jia Wu, Jianjun Zhang, Christopher I Amos, Chao Cheng

Faculty, Staff and Student Publications

No abstract provided.

American College Of Radiology Manual On Mr Safety: 2024 Update And Revisions, Ivan Pedrosa, David A Altman, Jonathan R Dillman, Michael N Hoff, Alexander M Mckinney, Jeffrey M Rogg, James A Webb, Dina L Hernandez, Robert E Watson

Faculty, Staff and Student Publications

Since the introduction of the American College of Radiology (ACR) MRI safety guidelines in 2002, the indications for use of MRI in clinical care and research have continued to expand. Similarly, MRI technologies have evolved, with multiple field strengths now available for human imaging. While several publications have updated the ACR recommendations since the first guidelines, a single source in a structured format was lacking. Accordingly, the ACR Committee on MR Safety recently updated the online ACR Manual on MR Safety that compiles ACR recommendations for safe use of MRI equipment in humans into a single document. This review describes …

Crowd-Sourced Benchmarking Of Single-Sample Tumor Subclonal Reconstruction, Adriana Salcedo, Maxime Tarabichi, Alex Buchanan, Shadrielle M G Espiritu, Hongjiu Zhang, Tai-Hsien Ou Yang, Dimitris Anastassiou, Yuanfang Guan, Gun Ho Jang, Mohammed F E Mootor, Kerstin Haase, Amit G Deshwar, William Zou, Imaad Umar, Stefan Dentro, Jeff A Wintersinger, Kami Chiotti, Jonas Demeulemeester, Clemency Jolly, Lesia Sycza, Minjeong Ko, Pcawg Evolution And Heterogeneity Working Group, Smc-Het Participants, David C Wedge, Quaid D Morris, Kyle Ellrott, Peter Van Loo, Paul C Boutros

Faculty, Staff and Student Publications

Subclonal reconstruction algorithms use bulk DNA sequencing data to quantify parameters of tumor evolution, allowing an assessment of how cancers initiate, progress and respond to selective pressures. We launched the ICGC-TCGA (International Cancer Genome Consortium-The Cancer Genome Atlas) DREAM Somatic Mutation Calling Tumor Heterogeneity and Evolution Challenge to benchmark existing subclonal reconstruction algorithms. This 7-year community effort used cloud computing to benchmark 31 subclonal reconstruction algorithms on 51 simulated tumors. Algorithms were scored on seven independent tasks, leading to 12,061 total runs. Algorithm choice influenced performance substantially more than tumor features but purity-adjusted read depth, copy-number state and read mappability …

In Vivo Antibody Labeling Route And Fluorophore Dictate Labeling Efficiency, Sensitivity, And Longevity, Natalie B Hagan, Charles Inaku, Nikesh Kunder, Tayleur White, Thierry Iraguha, Kristen E Pauken

Faculty, Staff and Student Publications

Leukocytes migrate through the blood and extravasate into organs to surveil the host for infection or cancer. Recently, we demonstrated that intravenous (IV) anti-CD45.2 antibody labeling allowed for precise tracking of leukocyte migration. However, the narrow labeling window can make this approach challenging for tracking rare migration events. Here, we show that altering antibody administration route and fluorophore can significantly extend the antibody active labeling time. We found that while both IV and intraperitoneal (IP) anti-CD45.2 antibody labeled circulating leukocytes after injection, they had different kinetic properties that impacted labeling time and intensity. Quantification of circulating antibody revealed that while …

Correction To: Selinexor In Combination With Carboplatin And Paclitaxel In Patients With Advanced Solid Tumors: Results Of A Single-Center, Multi-Arm Phase Ib Study, Kyaw Z Thein, Daniel D Karp, Apostolia Tsimberidou, Jing Gong, Selma Sulovic, Denái R Milton, Filip Janku, Lacey Mcquinn, Bettzy A Stephen, Rivka Colen, Brett W Carter, Timothy A Yap, Sarina A Piha-Paul, Siqing Fu, Funda Meric-Bernstam, Aung Naing

Faculty, Staff and Student Publications

No abstract provided.

Manual Therapy For Fibrosis-Related Late Effect Dysphagia In Head And Neck Cancer Survivors: The Mantle Nonrandomized Clinical Trial, Holly Mcmillan, Carla L Warneke, Sheila Buoy, Christine Porsche, Kiara Savage, Clifton D Fuller

Faculty, Staff and Student Publications

Importance: Late radiation-associated dysphagia (RAD) after head and neck cancer (HNC) treatment is challenging and commonly treatment refractory, with fibrosis stiffening connective tissues and compressing peripheral nerve tracts, contributing to diminished strength and possibly denervation of swallowing muscles. Manual therapy (MT), while common for cancer-related pain and other indications, remains largely unstudied for fibrosis-related late RAD.

Objective: To determine the feasibility and safety of MT, estimate effect size and durability of MT for associated improvements in cervical range of motion (CROM), and examine functional outcomes after MT in survivors of HNC with fibrosis-related late RAD.

Design, setting, and participants: This …

A Plain Language Summary Of The Ascertain Trial: Oral Decitabine And Cedazuridine Versus Intravenous Decitabine For Mds Or Cmml, Guillermo Garcia-Manero, James Mccloskey, Elizabeth A Griffiths, Karen W L Yee, Amer M Zeidan, H Joachim Deeg, Mary-Margaret Keating, Nancy Zhu, Nashat Y Gabrail, Salman Fazal, Joseph Maly, Olatoyosi Odenike, Amy E Dezern, Casey L O'Connell, Gail J Roboz, Lambert Busque, Rena Buckstein, Harshad Amin, Brian Leber, Aditi Shastri, Aram Oganesian, Harold N Keer, Mohammad Azab, Michael R Savona

Faculty, Staff and Student Publications

What is this summary about?This summary describes results from a phase 3 clinical trial called ASCERTAIN.Researchers compared two treatments in people with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML), either of which can develop into acute myeloid leukemia (AML). One group was treated with oral decitabine and cedazuridine (oral DEC-C) and the other with intravenous decitabine.Treatment was given in a series of cycles. In the first cycle, people were randomly assigned to receive oral DEC-C or intravenous decitabine and then switched to the other treatment in the second cycle. After the first two cycles, everyone …

Nicotinic Acetylcholine Receptor Expression In Merkel Cell Carcinoma Is Associated With Clinical And Histopathologic Parameters, Christopher R Cunningham, Yiannis P Dimopoulos, Ian M García-Quiñones, Denái R Milton, Manuel Delgado-Vélez, Victor G Prieto, Leomar Y Ballester, Phyu P Aung

Faculty, Staff and Student Publications

Background: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy with neuroendocrine differentiation. Several molecular pathways have been implicated in MCC development and multiple cell-of-origin candidates have been proposed, including neural crest cells, which express acetylcholine receptors (AChRs). The role of nicotinic acetylcholine receptors (nAChRs) in MCC has not been explored. In this study, we investigated if MCC expresses nAChRs and if nAChR expression correlates with patient characteristics.

Methods: The study included 71 MCC cases diagnosed with sufficient tissue available to perform immunohistochemical analysis. The median follow-up was 29.8 months (range, 2.7-234.1). We performed immunohistochemistry using antibodies against the …

Unraveling Heart Failure Phenotypes: A Systematic Review And Meta-Analysis Of Peak Oxygen Uptake And Its Determinants, Corey R Tomczak, Stephen J Foulkes, Christopher Weinkauf, Devyn Walesiak, Jing Wang, Sarah Paterson, Michael D Nelson, Simon Wernhart, Jan Vontobel, David Niederseer, Mark J Haykowsky

Faculty, Staff and Student Publications

Background: Understanding the impact of heart failure (HF) phenotype on peak oxygen uptake (peak ˙V O2) is essential for advancing personalized treatment strategies and enhancing patient outcomes. Therefore, we conducted a systematic review and meta-analysis of the evidence examining differences in peak ˙V O2 (primary objective) and its determinants (secondary objectives) between patients with HF with reduced (HFrEF) or preserved ejection fraction (HFpEF).

Methods: Studies comparing peak ˙V O2 in HFrEF vs HFpEF were found through PubMed (1967-2024), Scopus (1981-2024), and Web of Science (1985-2024). Data extraction and methodologic quality assessment were completed by 2 independent coders. Differences between HFrEF …

Insulin-Like Growth Factor 2 As A Driving Force For Exponential Expansion And Differentiation Of The Neonatal Thymus, Seung Woo Kang, Bryan R Helm, Yu Wang, Shiyun Xiao, Wen Zhang, Ken S Lau, Ellen R Richie, Laura P Hale, Nancy R Manley

Faculty, Staff and Student Publications

Like all organs, the thymus grows in size and function rapidly during development, but this growth comes to a halt after birth. However, the molecular mechanisms behind such a transition in the thymus remain obscure. Using single-cell RNA sequencing (scRNA-seq) of the murine thymic stroma, we identified that major transcriptomic changes occur in the endothelium and mesenchyme across the transition to homeostasis. Differentially expressed gene and intercellular network analyses of temporally resolved scRNA-seq data revealed fibroblast-derived insulin-like growth factor 2 (IGF2) as a candidate driving neonatal thymic expansion. We demonstrated that IGF2 activity promotes a cortical thymic epithelial cell-specific proliferation …

Long Term Results Of Venetoclax Combined With Flag-Ida Induction And Consolidation For Newly Diagnosed And Relapsed Or Refractory Acute Myeloid Leukemia, Courtney D Dinardo, Wei-Ying Jen, Koichi Takahashi, Tapan M Kadia, Sanam Loghavi, Lianchun Xiao, Ghayas C Issa, Nicholas J Short, Koji Sasaki, Sa A Wang, Jillian K Mullin, Sherry Pierce, Corey Bradley, Gautam Borthakur, Abhishek Maiti, Yesid Alvarado, Naveen Pemmaraju, Alessandra Ferrajoli, Mahesh Swaminathan, Maro Ohanian, Hussein A Abbas, Danielle Hammond, Jan Burger, Fadi Haddad, Guillermo Montalban-Bravo, Kelly Chien, Lucia Masarova, Musa Yilmaz, Nitin Jain, Michael Andreeff, Guillermo Garcia-Manero, Steven Kornblau, Farhad Ravandi, Elias Jabbour, Marina Y Konopleva, Hagop M Kantarjian

Faculty, Staff and Student Publications

Intensive chemotherapy remains the standard for newly diagnosed (ND) acute myeloid leukemia (AML); however, relapse risk remains high. Additionally, most patients with relapsed/refractory (RR) AML have poor outcomes. We report the long-term experience of 138 patients, 77 ND and 61 RR, treated with FLAG-IDA in combination with venetoclax. In the ND cohort, the overall response rate (ORR) was 97%, with a composite complete remission (CRc) rate of 95% and undetectable measurable residual disease (MRD) status by flow cytometry in 90%. The 3-year OS and EFS rates were 66 and 64%, respectively. Outcomes were similar across European LeukemiaNet (ELN) 2022 risk …

Lysyl Hydroxylase 2 Glucosylates Collagen Vi To Drive Lung Cancer Progression, Shike Wang, Houfu Guo, Reo Fukushima, Masahiko Terajima, Min Liu, Lenka Koudelková, Xin Liu, Jiang Yu, Emma Burris, Jun Xu, Alvise Schiavinato, William K Russell, Mitsuo Yamauchi, Xiaochao Tan, Jonathan M Kurie

Faculty, Staff and Student Publications

Lysyl hydroxylase 2 (LH2) is highly expressed in multiple tumor types and accelerates disease progression by hydroxylating lysine residues on fibrillar collagen telopeptides to generate stable collagen cross links in tumor stroma. Here, we show that a galactosylhydroxylysyl glucosyltransferase (GGT) domain on LH2-modified type-VI collagen (Col6) to promote lung adenocarcinoma (LUAD) growth and metastasis. In tumors generated by LUAD cells lacking LH2 GGT domain activity, stroma was less stiff, and stable types of collagen cross links were reduced. Mass spectrometric analysis of total and glycosylated peptides in parental and GGT-inactive tumor samples identified Col6 chain α3 (Col6a3), a component of …

Differentiation Stage Predicts Radiosensitivity In Mesenchymal-Like Pancreatic Cancer, Tingshi Su, Xinjian Yu, Mojtaba Hoseini-Ghahfarokhi, David B Flint, Scott J Bright, David K J Martinus, Mariam Ben Kacem, Poliana C Marinello, Eurico J G Pereira, Hua-Sheng Chiu, Uwe Titt, David R Grosshans, Jan Schuemann, Henning Willers, Harald Paganetti, Pavel Sumazin, Gabriel O Sawakuchi

Faculty, Staff and Student Publications

Purpose: To derive a genomic classifier to predict radiosensitivity of pancreatic cancer cell lines and patients with pancreatic cancer to allow genomic-guided radiation therapy.

Methods and materials: We collected a comprehensive data set of full clonogenic cell survival curves of 45 pancreatic cancer cell lines irradiated with clinical photon and proton beams. We derived classifiers based on data from human embryonic and fetal pancreas single-cell RNA-sequencing to distinguish between epithelial and mesenchymal cells and to predict pancreas cell-line differentiation stage. Independent testing was done with an embryonic mouse pancreas single-cell RNA-sequencing data set. We then used bulk RNA-seq profiles from …

Vitamin D-Related Genetic Variants And Prostate Cancer Risk In Black Men, Tracy M Layne, Joseph H Rothstein, Xiaoyu Song, Shaneda Warren Andersen, Emma K T Benn, Robert J Klein

Faculty, Staff and Student Publications

Background: The relationship between vitamin D and prostate cancer has primarily been characterized among White men. Black men, however, have higher prostate cancer incidence and mortality rates, chronically low circulating vitamin D levels, and ancestry-specific genetic variants in vitamin D-related genes. Here, we examine critical genes in the vitamin D pathway and prostate cancer risk in Black men.

Methods: We assessed a total of 73 candidate variants in genes (namely GC, CYP27A1, CYP27B1, CYP24A1, VDR, and RXRA) including functional variants previously associated with prostate cancer and circulating 25(OHD) in White men. Associations with prostate cancer risk were examined using genome-wide …

Cost-Effectiveness Of Personalized Policies For Implementing Organ-At-Risk Sparing Adaptive Radiation Therapy In Head And Neck Cancer, Seyedmohammadhossein Hosseinian, Daniel Suarez-Aguirre, Cem Dede, Raul Garcia, Lucas Mccullum, Aysenur Karagoz, Stephen Y Lai, Katherine A Hutcheson, Amy C Moreno, Kristy K Brock, Fatemeh Nosrat, Clifton D Fuller, Andrew J Schaefer

Faculty, Staff and Student Publications

Background and purpose: The principle of adaptive radiation therapy (ART) is to adjust radiation plans in response to anatomical changes during treatment. The purpose of this study was to develop a decision-making model for implementation of personalized ART that balances the costs and clinical benefits of radiation plan adaptations in head and neck cancer (HNC).

Materials and methods: Using retrospective imaging data from 52 HNC patients, a Markov decision process (MDP) model was developed to determine optimal timing for plan adaptations based on the difference in normal tissue complication probability (ΔNTCP) between planned and delivered doses to organs-at-risk. To capture …

Defining A 'Cells To Society' Research Framework For Appendiceal Tumours, Andreana N Holowatyj, Michael J Overman, Konstantinos I Votanopoulos, Andrew M Lowy, Patrick Wagner, Cathy Eng, Richard M Goldberg, Mojgan Hosseini, Kamran Idrees, Douglas B Johnson, Ardaman Shergill, Erin Ward, Nicholas C Zachos, Deborah Shelton

Faculty, Staff and Student Publications

Tumours of the appendix — a vestigial digestive organ attached to the colon — are rare. Although we estimate that around 3,000 new appendiceal cancer cases are diagnosed annually in the USA, the challenges of accurately diagnosing and identifying this tumour type suggest that this number may underestimate true population incidence. In the current absence of disease-specific screening and diagnostic imaging modalities, or well-established risk factors, the incidental discovery of appendix tumours is often prompted by acute presentations mimicking appendicitis or when the tumour has already spread into the abdominal cavity — wherein the potential misclassification of appendiceal tumours as …

Uncertainty-Guided Pancreatic Tumor Auto-Segmentation With Tversky Ensemble, Cenji Yu, Skylar S Gay, Aashish C Gupta, Rachael M Martin-Paulpeter, Ethan B Ludmir, Yao Zhao, Jack Duryea, Xinru Chen, Carlos E Cardenas, Jinzhong Yang, Albert C Koong, Tucker J Netherton, Dong Joo Rhee, Laurence E Court

Faculty, Staff and Student Publications

Background and purpose: Pancreatic gross tumor volume (GTV) delineation is challenging due to their variable morphology and uncertain ground truth. Previous deep learning-based auto-segmentation methods have struggled to handle tasks with uncertain ground truth and have not accommodated stylistic customizations. We aim to develop a human-in-the-loop pancreatic GTV segmentation tool using Tversky ensembles by leveraging uncertainty estimation techniques.

Material and methods: In this study, we utilized a total of 282 patients from the pancreas task of the Medical Segmentation Decathlon. Thirty patients were randomly selected to form an independent test set, while the remaining 252 patients were divided into an …

The Cgas-Sting1 Pathway As A Mediator Of Innate Immune Response In Cardiovascular Disease, Leila Rouhi, Priyatansh Gurha, Ali J Marian

Faculty, Staff and Student Publications

The innate immune response, a rapid and cell-autonomous response of the cell to the pathogens, recognizes the external as well as the internal pathogens, such as self-DNA, released from the damaged cells. The response activates a set of molecules that induce the expression of proinflammatory cytokines and chemokines and leads to inflammation, fibrosis, and cell death. The innate immune response comprised of DNA-sensing protein cyclic guanosine monophosphate-adenosine monophosphate synthase (CGAS) and its downstream molecules, the stimulator of interferon genes 1 (STING1), TANK-binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), and nuclear factor kappa B (NFκB), are activated in several …

Role Of Peripheral Amyloid-Β Aggregates In Alzheimer's Disease: Mechanistic, Diagnostic, And Therapeutic Implications, Nazaret Gamez, Rodrigo Morales

Faculty, Staff and Student Publications

No abstract provided.

Guidelines For The Management Of Pancreatic Cystic Lesions: Many Options, Too Few Solutions?, Yifan Wang, Michael P Kim

Faculty, Staff and Student Publications

No abstract provided.

Prediction Of Grade 4 Radiation-Induced Lymphopenia During Chemoradiation Therapy For Lung Cancer Patients: Insights From Two Past Trials, Serena Monti, Giuseppe Palma, Ting Xu, Radhe Mohan, Zhongxing Liao

Faculty, Staff and Student Publications

Background and purpose: Radiation-induced lymphopenia (RIL) is a significant side effect associated with radiation therapy (RT) with important prognostic implications. We developed and tested a normal tissue complication probability (NTCP) model for Grade 4 (G4) RIL in patients with locally advanced Non-Small-Cell Lung Cancer (NSCLC) who underwent concurrent chemotherapy and RT, analyzing data from patients enrolled in two clinical trials.

Materials and methods: We retrospectively analyzed the data from NCT00915005 (MDA-cohort) and NCT00533949 (RTOG0617-cohort) trials. After finding the candidate predictors of G4-RIL, defined as absolute lymphocyte count (ALC) at nadir < 0.2*109 cells/l during RT, we trained an NTCP model on the MDA-cohort and tested it on the RTOG-cohort, based on common available variables in the two cohorts. Model performance was assessed in terms of discrimination and calibration.

Results: In the MDA-cohort, 55 out of 161 (34%) patients …