Biomedical Informatics Commons^™

Hiv-1 Vpu Protein Forms Stable Oligomers In Aqueous Solution Via Its Transmembrane Domain Self-Association, Saman Majeed, Lan Dang, Md Majharul Islam, Olamide Ishola, Peter P Borbat, Steven J Ludtke, Elka R Georgieva

Faculty, Staff and Students Publications

We report our findings on the assembly of the HIV-1 protein Vpu into soluble oligomers. Vpu is a key HIV-1 protein. It has been considered exclusively a single-pass membrane protein. Previous observations show that this protein forms stable oligomers in aqueous solution, but details about these oligomers still remain obscure. This is an interesting and rather unique observation, as the number of proteins transitioning between soluble and membrane embedded states is limited. In this study we made use of protein engineering, size exclusion chromatography, cryoEM and electron paramagnetic resonance (EPR) spectroscopy to better elucidate the nature of the soluble oligomers. …

Patient-Reported Outcomes Of Omission Of Breast Surgery Following Neoadjuvant Systemic Therapy: A Nonrandomized Clinical Trial, Helen M Johnson, Heather Lin, Yu Shen, Emilia J Diego, Savitri Krishnamurthy, Wei T Yang, Benjamin D Smith, Vicente Valero, Anthony Lucci, Susie X Sun, Simona F Shaitelman, Melissa P Mitchell, Judy C Boughey, Richard L White, Gaiane M Rauch, Henry M Kuerer

Faculty, Staff and Student Publications

IMPORTANCE: Patients should have an active role in decisions about pursuing or forgoing specific therapies in treatment de-escalation trials.

OBJECTIVE: To evaluate longitudinal patient-reported outcomes (PROs) encompassing decisional comfort and health-related quality of life (HRQOL) among patients who elected to enroll in a clinical trial evaluating radiotherapy alone, without breast surgery, for invasive breast cancers with exceptional response to neoadjuvant systemic therapy (NST).

DESIGN, SETTING, AND PARTICIPANTS: Prospective, single-group, phase 2 clinical trial at 7 US medical centers. Women aged 40 years or older with invasive cT1-2 N0-1 M0 triple-negative or human epidermal growth factor receptor 2 (ERBB2)-positive breast cancer …

Epidermal Growth Factor Receptor-Targeted Neoantigen Peptide Vaccination For The Treatment Of Non-Small Cell Lung Cancer And Glioblastoma, Fenge Li, Huancheng Wu, Xueming Du, Yimo Sun, Barbara Nassif Rausseo, Amjad Talukder, Arjun Katailiha, Lama Elzohary, Yupeng Wang, Zhiyu Wang, Gregory Lizée

Faculty, Staff and Student Publications

The epidermal growth factor receptor (EGFR) plays crucial roles in several important biological functions such as embryogenesis, epithelial tissue development, and cellular regeneration. However, in multiple solid tumor types overexpression and/or activating mutations of the EGFR gene frequently occur, thus hijacking the EGFR signaling pathway to promote tumorigenesis. Non-small cell lung cancer (NSCLC) tumors in particular often contain prevalent and shared EGFR mutations that provide an ideal source for public neoantigens (NeoAg). Studies in both humans and animal models have confirmed the immunogenicity of some of these NeoAg peptides, suggesting that they may constitute viable targets for cancer immunotherapies. Peptide …

Evolutionary Action-Machine Learning Model Identifies Candidate Genes Associated With Early-Onset Coronary Artery Disease, Dillon Shapiro, Kwanghyuk Lee, Jennifer Asmussen, Thomas Bourquard, Olivier Lichtarge

Faculty, Staff and Students Publications

Background Coronary artery disease is a primary cause of death around the world, with both genetic and environmental risk factors. Although genome-wide association studies have linked >100 unique loci to its genetic basis, these only explain a fraction of disease heritability. Methods and Results To find additional gene drivers of coronary artery disease, we applied machine learning to quantitative evolutionary information on the impact of coding variants in whole exomes from the Myocardial Infarction Genetics Consortium. Using ensemble-based supervised learning, the Evolutionary Action-Machine Learning framework ranked each gene's ability to classify case and control samples and identified 79 significant associations. …

Genetic Susceptibility To Cognitive Decline Following Craniospinal Irradiation For Pediatric Central Nervous System Tumors, Austin L Brown, Pagna Sok, Kimberly P Raghubar, Philip J Lupo, Melissa A Richard, Alanna C Morrison, Jun J Yang, Clinton F Stewart, Mehmet Fatih Okcu, Murali M Chintagumpala, Amar Gajjar, Lisa S Kahalley, Heather Conklin, Michael E Scheurer

Faculty, Staff and Student Publications

BACKGROUND: Survivors of pediatric central nervous system (CNS) tumors treated with craniospinal irradiation (CSI) exhibit long-term cognitive difficulties. Goals of this study were to evaluate longitudinal effects of candidate and novel genetic variants on cognitive decline following CSI.

METHODS: Intelligence quotient (IQ), working memory (WM), and processing speed (PS) were longitudinally collected from patients treated with CSI (n = 241). Genotype-by-time interactions were evaluated using mixed-effects linear regression to identify common variants (minor allele frequency > 1%) associated with cognitive performance change. Novel variants associated with cognitive decline (P < 5 × 10-5) in individuals of European ancestry (n = 163) were considered replicated if they demonstrated consistent genotype-by-time interactions (P < .05) in individuals of non-European ancestries (n = 78) and achieved genome-wide statistical significance (P < 5 × 10-8) in a meta-analysis across ancestry groups.

RESULTS: Participants were mostly males (65%) diagnosed with embryonal tumors (98%) at …

Low-Grade Serous Ovarian Cancer: Expert Consensus Report On The State Of The Science, Rachel N Grisham, Brian M Slomovitz, Nicole Andrews, Susana Banerjee, Jubilee Brown, Mark S Carey, Herman Chui, Robert L Coleman, Amanda N Fader, Stephanie Gaillard, Charlie Gourley, Anil K Sood, Bradley J Monk, Kathleen N Moore, Isabelle Ray-Coquard, Ie-Ming Shih, Shannon N Westin, Kwong-Kwok Wong, David M Gershenson

Faculty, Staff and Student Publications

Compared with high-grade serous carcinoma, low-grade serous carcinoma of the ovary or peritoneum is a less frequent epithelial ovarian cancer type that is poorly sensitive to chemotherapy and affects younger women, many of whom endure years of ineffective treatments and poor quality of life. The pathogenesis of this disease and its management remain incompletely understood. However, recent advances in the molecular characterization of the disease and identification of novel targeted therapies with activity in low-grade serous carcinoma offer the promise of improved outcomes. To update clinicians regarding recent scientific and clinical trial advancements and discuss unanswered questions related to low-grade …

Evaluation Of In Vitro Antioxidant, Anti-Obesity, And Anti-Diabetic Activities Of, Alaa S Mohamed, Essam Mohamed Elsebaie, Wesam Mohammed Abdelrhman, Nabila Yahia Mahmoud Abdulmaguid, Rasha M Bahnasy, Manal Salah Abbas Elgendy, Arwa Mohamed Mohamed Mahmoud Elashry, Marwa Fawzy El-Hassanin, Nora Hamdy Mouhamed El-Wakeil, Azhar Mostafa Mohamed Khalil, Hesham F Amin

Faculty, Staff and Student Publications

Opuntia ficus cladodes (OFC) are considered one of the wastes that result from opuntia cultivation, and their disposal by traditional methods results in many environmental problems. Therefore, this study was conducted with two aims. The first was the production of OFC gel, and the evaluation of its in vitro antioxidant (by two methods, DPPH and ABTS), anti-obesity, and anti-diabetic activities. The second was an investigation of the effects of different concentrations of this gel (0, 50, and 100%) as an edible coating on the quality of shrimp during 8 days of refrigerated storage. The results showed that this gel was …

The Characterization And Evaluation Of The Soluble Triggering Receptor Expressed On Myeloid Cells-Like Transcript-1 In Stable Coronary Artery Disease, Zaida Bayrón-Marrero, Siobhan Branfield, Javier Menéndez-Pérez, Benjamín Nieves-López, Laura Ospina, Yadira Cantres-Rosario, Loyda M Melendez, Robert Hunter, Angelia Gibson, Gerónimo Maldonado-Martínez, A Valance Washington

Faculty, Staff and Student Publications

Platelets play crucial roles in the development and progression of coronary artery disease (CAD). The triggering receptor expressed in myeloid cells-like transcript-1 (TLT-1) is stored in platelet α granules, and activated platelets release a soluble fragment (sTLT-1). We set out to better characterize the constituent amino acids of sTLT-1 and to evaluate sTLT-1 for use as a biomarker in patients with stable CAD. We evaluated sTLT-1 release using immunoprecipitation and mass spectrometry and employed statistical methods to retrospectively correlate sTLT-1 concentrations, utilizing ELISA in plasma samples from 1510 patients with documented stable CAD. We identified TLT-1 residues to 133 in …

Taz2 Truncation Confers Overactivation Of P300 And Cellular Vulnerability To Hdac Inhibition, Longxia Xu, Hongwen Xuan, Wei He, Liang Zhang, Mengying Huang, Kuai Li, Hong Wen, Han Xu, Xiaobing Shi

Faculty, Staff and Student Publications

The histone acetyltransferase p300/CBP is composed of several conserved domains, among which, the TAZ2 domain is known as a protein-protein interaction domain that binds to E1A and various transcription factors. Here we show that TAZ2 has a HAT autoinhibitory function. Truncating p300/CBP at TAZ2 leads to hyperactive HAT and elevated histone H3K27 and H3K18 acetylation in cells. Mechanistically, TAZ2 cooperates with other HAT neighboring domains to maintain the HAT active site in a 'closed' state. Truncating TAZ2 or binding of transcription factors to TAZ2 induces a conformational change that 'opens' the active site for substrate acetylation. Importantly, genetic mutations that …

Aenmd: Annotating Escape From Nonsense-Mediated Decay For Transcripts With Protein-Truncating Variants, Jonathan Klonowski, Qianqian Liang, Zeynep Coban-Akdemir, Cecilia Lo, Dennis Kostka

Faculty, Staff and Student Publications

DNA changes that cause premature termination codons (PTCs) represent a large fraction of clinically relevant pathogenic genomic variation. Typically, PTCs induce transcript degradation by nonsense-mediated mRNA decay (NMD) and render such changes loss-of-function alleles. However, certain PTC-containing transcripts escape NMD and can exert dominant-negative or gain-of-function (DN/GOF) effects. Therefore, systematic identification of human PTC-causing variants and their susceptibility to NMD contributes to the investigation of the role of DN/GOF alleles in human disease. Here we present aenmd, a software for annotating PTC-containing transcript-variant pairs for predicted escape from NMD. aenmd is user-friendly and self-contained. It offers functionality not currently available …

Hospitalizations Among Adults With Ckd In Public Renal Specialty Practices: A Retrospective Study From Queensland, Australia, Vishal Diwan, Wendy E Hoy, Zaimin Wang, Jianzhen Zhang, Anne Cameron, Sree K Venuthurupalli, Robert G Fassett, Samuel Chan, Helen G Healy, Ken-Soon Tan, Richard Baer, Andrew J Mallett, Nicholas Gray, Murty Mantha, Roy Cherian, Clyson Mutatiri, Krishan Madhan, George Kan, Geoffrey Mitchell, Shahadat Hossain, Danielle Wu, Thin Han, Adrian Kark, Thomas Titus, Dwarakanatan Ranganathan, Ann Bonner, Sridevi Govindarajulu, Nhmrc Ckd.Cre And The Ckd.Qld Collaborative

Faculty, Staff and Student Publications

RATIONALE & OBJECTIVE: Little is known about hospital admissions in nondialysis patients with chronic kidney disease (CKD) before death or starting kidney replacement therapy (KRT).

STUDY DESIGN: Retrospective observational cohort study.

SETTING & PARTICIPANTS: Hospitalizations among 7,201 patients with CKD from 10 public renal clinics in Queensland (QLD), enrolled in the CKD.QLD registry starting in May 2011, were followed for 25,496.34 person-years until they started receiving KRT or died, or until June 30, 2018.

PREDICTORS: Demographic and clinical characteristics of patients with CKD.

OUTCOMES: Hospital admissions.

ANALYTICAL APPROACH: We evaluated the association of demographic and clinical features with hospitalizations, length …

Efficient Targeted Learning Of Heterogeneous Treatment Effects For Multiple Subgroups, Waverly Wei, Maya Petersen, Mark J Van Der Laan, Zeyu Zheng, Chong Wu, Jingshen Wang

Faculty, Staff and Student Publications

In biomedical science, analyzing treatment effect heterogeneity plays an essential role in assisting personalized medicine. The main goals of analyzing treatment effect heterogeneity include estimating treatment effects in clinically relevant subgroups and predicting whether a patient subpopulation might benefit from a particular treatment. Conventional approaches often evaluate the subgroup treatment effects via parametric modeling and can thus be susceptible to model mis-specifications. In this paper, we take a model-free semiparametric perspective and aim to efficiently evaluate the heterogeneous treatment effects of multiple subgroups simultaneously under the one-step targeted maximum-likelihood estimation (TMLE) framework. When the number of subgroups is large, we …

Mpla Case: How Do You Lead As A Lead Physicist?, Patricia Sansourekidou, Leonard Kim, Lee Xu, Mary Gronberg, Cassandra Stambaugh, Dongxu Wang

Faculty, Staff and Student Publications

This work of fiction is part of a case study series developed by the Medical Physics Leadership Academy (MPLA). It is intended to facilitate the discussion of the managerial and leadership challenges faced by a clinical medical physicist. In this case, a physicist David used to work in a clinic where he thrived and felt like a leader, despite not having the title. After a job change, he is now officially the "Lead Physicist" at a hospital newly affiliated with a large academic healthcare system. He believes he will be equally successful. Yet he struggles to bring about changes and …

Longitudinal Diffusion And Volumetric Kinetics Of Head And Neck Cancer Magnetic Resonance On A 15 T Mr-Linear Accelerator Hybrid System: A Prospective R-Ideal Stage 2a Imaging Biomarker Characterization/Pre-Qualification Study, Joint Head And Neck Radiation Therapy-Mri Development Cooperative, Mr-Linac Consortium Head And Neck Tumor Site Group

Faculty, Staff and Student Publications

OBJECTIVES: We aim to characterize the serial quantitative apparent diffusion coefficient (ADC) changes of the target disease volume using diffusion-weighted imaging (DWI) acquired weekly during radiation therapy (RT) on a 1.5 T MR-Linac and correlate these changes with tumor response and oncologic outcomes for head and neck squamous cell carcinoma (HNSCC) patients as part of a programmatic R-IDEAL biomarker characterization effort.

METHODS: Thirty patients with HNSCC who received curative-intent RT at MD Anderson Cancer Center, were included. Baseline and weekly MRI were obtained, and various ADC parameters were extracted from the regions of interest (ROIs). Baseline and weekly ADC parameters …

Going Circular: History, Present, And Future Of Circrnas In Cancer, Giuseppina Pisignano, David C Michael, Tanvi H Visal, Radu Pirlog, Michael Ladomery, George A Calin

Faculty, Staff and Student Publications

To date, thousands of highly abundant and conserved single-stranded RNA molecules shaped into ring structures (circRNAs) have been identified. CircRNAs are multifunctional molecules that have been shown to regulate gene expression transcriptionally and post-transcriptionally and exhibit distinct tissue- and development-specific expression patterns associated with a variety of normal and disease conditions, including cancer pathogenesis. Over the past years, due to their intrinsic stability and resistance to ribonucleases, particular attention has been drawn to their use as reliable diagnostic and prognostic biomarkers in cancer diagnosis, treatment, and prevention. However, there are some critical caveats to their utility in the clinic. Their …

Design Of A Phase Iii, Double-Blind, Randomised, Placebo-Controlled Trial Of Bi 1015550 In Patients With Progressive Pulmonary Fibrosis (Fibroneer-Ild), Toby M Maher, Shervin Assassi, Arata Azuma, Vincent Cottin, Anna-Maria Hoffmann-Vold, Michael Kreuter, Justin M Oldham, Luca Richeldi, Claudia Valenzuela, Marlies S Wijsenbeek, Carl Coeck, Christina Schlecker, Florian Voss, Daniel Wachtlin, Fernando J Martinez

Faculty, Staff and Student Publications

INTRODUCTION: Progressive pulmonary fibrosis (PPF) includes any diagnosis of progressive fibrotic interstitial lung disease (ILD) other than idiopathic pulmonary fibrosis (IPF). However, disease progression appears comparable between PPF and IPF, suggesting a similar underlying pathology relating to pulmonary fibrosis. Following positive results in a phase II study in IPF, this phase III study will investigate the efficacy and safety of BI 1015550 in patients with PPF (FIBRONEER-ILD).

METHODS AND ANALYSIS: In this phase III, double-blind, placebo-controlled trial, patients are being randomised 1:1:1 to receive BI 1015550 (9 mg or 18 mg) or placebo twice daily over at least 52 weeks, …

Carm1 Arginine Methyltransferase As A Therapeutic Target For Cancer, Margarida Santos, Jee Won Hwang, Mark T Bedford

Faculty, Staff and Student Publications

Coactivator-associated arginine methyltransferase 1 (CARM1) is an arginine methyltransferase that posttranslationally modifies proteins that regulate multiple levels of RNA production and processing. Its substrates include histones, transcription factors, coregulators of transcription, and splicing factors. CARM1 is overexpressed in many different cancer types, and often promotes transcription factor programs that are co-opted as drivers of the transformed cell state, a process known as transcription factor addiction. Targeting these oncogenic transcription factor pathways is difficult but could be addressed by removing the activity of the key coactivators on which they rely. CARM1 is ubiquitously expressed, and its KO is less detrimental in …

Aerobic Exercise Alters The Melanoma Microenvironment And Modulates Erk5 S496 Phosphorylation, Hannah Savage, Sumedha Pareek, Jonghae Lee, Riccardo Ballarò, Darlan Conterno Minussi, Karma Hayek, Mumina Sadullozoda, Brooke S Lochmann, Jennifer L Mcquade, Emily C Lavoy, Enrica Marmonti, Hetal Patel, Guangyu Wang, Masaki Imanishi, Sivareddy Kotla, Jun-Ichi Abe, Keri Schadler

Faculty, Staff and Student Publications

Exercise changes the tumor microenvironment by remodeling blood vessels and increasing infiltration by cytotoxic immune cells. The mechanisms driving these changes remain unclear. Herein, we demonstrate that exercise normalizes tumor vasculature and upregulates endothelial expression of VCAM1 in YUMMER 1.7 and B16F10 murine models of melanoma but differentially regulates tumor growth, hypoxia, and the immune response. We found that exercise suppressed tumor growth and increased CD8+ T-cell infiltration in YUMMER but not in B16F10 tumors. Single-cell RNA sequencing and flow cytometry revealed exercise modulated the number and phenotype of tumor-infiltrating CD8+ T cells and myeloid cells. Specifically, exercise caused a …

Cytoreductive Nephrectomy For Patients With Metastatic Sarcomatoid And/Or Rhabdoid Renal Cell Carcinoma Treated With Immune Checkpoint Therapy, Andrew W Hahn, Ritesh R Kotecha, Paul V Viscuse, Alberto C Pieretti, Andrew J Wiele, Eric Jonasch, Chung-Han Lee, Jianjun Gao, Amado J Zurita, Amishi Y Shah, Matthew T Campbell, Padmanee Sharma, Robert J Motzer, Paul Russo, Christopher G Wood, Nizar M Tannir, Martin H Voss, Jose A Karam, A Ari Hakimi, Pavlos Msaouel

Faculty, Staff and Student Publications

BACKGROUND: Renal cell carcinoma (RCC) with sarcomatoid and/or rhabdoid (S/R) dedifferentiation is a highly aggressive tumor with a poor prognosis. Immune checkpoint therapy (ICT) has shown significant treatment efficacy in this subtype. There remains uncertainly regarding the role of cytoreductive nephrectomy (CN) for patients with metastatic RCC (mRCC) with S/R who received ICT.

OBJECTIVE: Here, we report the outcomes with ICT for patients with mRCC and S/R dedifferentiation by CN status.

DESIGN, SETTING, AND PARTICIPANTS: A retrospective review was conducted of 157 patients with sarcomatoid, rhabdoid, or sarcomatoid plus rhabdoid dedifferentiation who received an ICT-based regimen at two cancer centers. …

Association Between Duration Of Smoking Abstinence Before Non-Small-Cell Lung Cancer Diagnosis And Survival: A Retrospective, Pooled Analysis Of Cohort Studies, Aline F Fares, Yao Li, Mei Jiang, M Catherine Brown, Andrew C L Lam, Reenika Aggarwal, Sabine Schmid, Natasha B Leighl, Frances A Shepherd, Zhichao Wang, Nancy Diao, Angela S Wenzlaff, Juntao Xie, Takashi Kohno, Neil E Caporaso, Curtis Harris, Hongxia Ma, Matthew J Barnett, Leticia Ferro Leal, G Fernandez-Tardon, Mónica Pérez-Ríos, Michael P A Davies, Fiona Taylor, Ben Schöttker, Paul Brennan, David Zaridze, Ivana Holcatova, Jolanta Lissowska, Beata Świątkowska, Dana Mates, Milan Savic, Hermann Brenner, Angeline Andrew, Angela Cox, John K Field, Alberto Ruano-Ravina, Sanjay S Shete, Adonina Tardon, Ying Wang, Loic Le Marchand, Rui Manuel Reis, Matthew B Schabath, Chu Chen, Hongbing Shen, Brid M Ryan, Maria Teresa Landi, Kouya Shiraishi, Jie Zhang, Ann G Schwartz, Ming S Tsao, David C Christiani, Ping Yang, Rayjean J Hung, Wei Xu, Geoffrey Liu

Faculty, Staff and Student Publications

BACKGROUND: The association between duration of smoking abstinence before non-small-cell lung cancer (NSCLC) diagnosis and subsequent survival can influence public health messaging delivered in lung-cancer screening. We aimed to assess whether the duration of smoking abstinence before diagnosis of NSCLC is associated with improved survival.

METHODS: In this retrospective, pooled analysis of cohort studies, we used 26 cohorts participating in Clinical Outcomes Studies of the International Lung Cancer Consortium (COS-ILCCO) at 23 hospitals. 16 (62%) were from North America, six (23%) were from Europe, three (12%) were from Asia, and one (4%) was from South America. Patients enrolled were diagnosed …

Impact Of Serial Intralesional Steroid Injections On Idiopathic Subglottic Stenosis, Matthew R Hoffman, Ankita Patro, Li-Ching Huang, Sheau-Chiann Chen, Lynn D Berry, Alexander Gelbard, David O Francis

Faculty, Staff and Student Publications

OBJECTIVES: Serial intralesional steroid injection (SILSI) has been increasingly used to treat idiopathic subglottic stenosis (iSGS). Prior studies have shown effectiveness, but not in all patients. This multi-institutional study evaluates the effect of SILSI on time to recurrent operation, peak expiratory flow (PEF), and dyspnea.

METHODS: Post-hoc secondary analysis of the North American Airway Collaborative data were performed to evaluate the outcomes of iSGS patients undergoing and not undergoing SILSI. The primary outcome was time to recurrent operation, evaluated using Kaplan-Meier curves and Cox regression analysis. Secondary outcomes were change in PEF and clinical chronic obstructive pulmonary disease questionnaire (CCQ) …

Lineage Plasticity And Stemness Phenotypes In Prostate Cancer: Harnessing The Power Of Integrated "Omics" Approaches To Explore Measurable Metrics, Souzana Logotheti, Eugenia Papadaki, Vasiliki Zolota, Christopher Logothetis, Aristidis G Vrahatis, Rama Soundararajan, Vasiliki Tzelepi

Faculty, Staff and Student Publications

Prostate cancer (PCa), the most frequent and second most lethal cancer type in men in developed countries, is a highly heterogeneous disease. PCa heterogeneity, therapy resistance, stemness, and lethal progression have been attributed to lineage plasticity, which refers to the ability of neoplastic cells to undergo phenotypic changes under microenvironmental pressures by switching between developmental cell states. What remains to be elucidated is how to identify measurements of lineage plasticity, how to implement them to inform preclinical and clinical research, and, further, how to classify patients and inform therapeutic strategies in the clinic. Recent research has highlighted the crucial role …

Quantitative Longitudinal Mapping Of Radiation-Treated Prostate Cancer Using Mr Fingerprinting With Radial Acquisition And Subspace Reconstruction, Victoria Y Yu, Ricardo Otazo, Can Wu, Ergys Subashi, Manuel Baumann, Peter Koken, Mariya Doneva, Peter Mazurkewitz, Daniel Shasha, Michael Zelefsky, Laura Cervino, Ouri Cohen

Faculty, Staff and Student Publications

MR fingerprinting (MRF) enables fast multiparametric quantitative imaging with a single acquisition and has been shown to improve diagnosis of prostate cancer. However, most prostate MRF studies were performed with spiral acquisitions that are sensitive to B0 inhomogeneities and consequent blurring. In this work, a radial MRF acquisition with a novel subspace reconstruction technique was developed to enable fast T1/T2 mapping in the prostate in under 4 min. The subspace reconstruction exploits the extensive temporal correlations in the MRF dictionary to pre-compute a low dimensional space for the solution and thus reduce the number of radial spokes to accelerate the …

Evaluating The Knowledge, Attitudes, And Practices Of Healthcare Workers Regarding High-Risk Nosocomial Infections: A Global Cross-Sectional Study, Elham M Khatrawi, Priyadarshi Prajjwal, Muhammad Farhan, Pugazhendi Inban, Shraddha Gurha, Saud M S Al-Ezzi, Mohammed D M Marsool, Prerna Ahuja, Mohammed A Mateen, Felix O Aina, Omniat A Hussin

Faculty, Staff and Student Publications

BACKGROUND: Healthcare workers (HCWs) play a vital role in delivering care and are frequently exposed to the risk of acquiring infections within the hospital setting. Around 15% of hospitalized patients suffer from these infections globally. However, the role and awareness of HCWs in the transmission of hospital-acquired infections (HAIs) or nosocomial infections is still unclear. This study aimed to evaluate the knowledge, attitude, and practices (KAP) toward high-risk microbial infections among HCWs on a global scale to identify measures to address this problem.

METHOD: A cross-sectional descriptive study was conducted between 2022 and 2023, with HCWs selected as the study …

Fibronectin Contributes To A Braf Inhibitor-Driven Invasive Phenotype In Thyroid Cancer Through Egr1, Which Can Be Blocked By Inhibition Of Erk1/2, Hannah M Hicks, Nikita Pozdeyev, Sharon B Sams, Umarani Pugazhenthi, Elise S Bales, Marie-Claude Hofmann, Logan R Mckenna, Rebecca E Schweppe

Faculty, Staff and Student Publications

Mutations in BRAF are common in advanced papillary and anaplastic thyroid cancer (PTC and ATC). However, patients with BRAF-mutant PTC currently lack therapies targeting this pathway. Despite the approved combination of BRAF and MEK1/2 inhibition for patients with BRAF-mutant ATC, these patients often progress. Thus, we screened a panel of BRAF-mutant thyroid cancer cell lines to identify new therapeutic strategies. We showed that thyroid cancer cells resistant to BRAF inhibition (BRAFi) exhibit an increase in invasion and a proinvasive secretome in response to BRAFi. Using reverse-phase protein array (RPPA), we identified a nearly 2-fold increase in expression of the extracellular …

Subsequent Female Breast Cancer Risk Associated With Anthracycline Chemotherapy For Childhood Cancer, Yuehan Wang, Cécile M Ronckers, Flora E Van Leeuwen, Chaya S Moskowitz, Wendy Leisenring, Gregory T Armstrong, Florent De Vathaire, Melissa M Hudson, Claudia E Kuehni, Michael A Arnold, Charlotte Demoor-Goldschmidt, Daniel M Green, Tara O Henderson, Rebecca M Howell, Matthew J Ehrhardt, Joseph P Neglia, Kevin C Oeffinger, Helena J H Van Der Pal, Leslie L Robison, Michael Schaapveld, Lucie M Turcotte, Nicolas Waespe, Leontien C M Kremer, Jop C Teepen

Faculty, Staff and Student Publications

Anthracycline-based chemotherapy is associated with increased subsequent breast cancer (SBC) risk in female childhood cancer survivors, but the current evidence is insufficient to support early breast cancer screening recommendations for survivors treated with anthracyclines. In this study, we pooled individual patient data of 17,903 survivors from six well-established studies, of whom 782 (4.4%) developed a SBC, and analyzed dose-dependent effects of individual anthracycline agents on developing SBC and interactions with chest radiotherapy. A dose-dependent increased SBC risk was seen for doxorubicin (hazard ratio (HR) per 100 mg m

Clinical Relevance Of Myc/Bcl2 Expression And Cell Of Origin In Patients With Diffuse Large B-Cell Lymphoma Treated With Autologous Transplant, Taha Al-Juhaishi, Yingjun Wang, Denái R Milton, Zijun Y Xu-Monette, Elias Jabbour, May Daher, Jin S Im, Qaiser Bashir, Swaminathan P Iyer, David Marin, Amanda L Olson, Uday Popat, Muzaffar Qazilbash, Gabriela Rondon, Alison M Gulbis, Richard E Champlin, Ken H Young, Issa F Khouri

Faculty, Staff and Student Publications

Dual expression of MYC and BCL2 proteins (double-expressor lymphoma [DEL]) as well as cell of origin (COO) are important prognostic factors in patients with diffuse large B-cell lymphoma (DLBCL) after conventional chemotherapy. We studied the prognostic impact of DEL and COO in patients with relapsed DLBCL treated with autologous stem cell transplant (ASCT). Three-hundred and three patients with stored tissue samples were identified. Classification was successful in 267 patients: 161 (60%) were DEL/non-double hit (DHL), 98 (37%) were non-DEL/non-DHL, and 8 (3%) were DEL/DHL. Compared to non-DEL/non-DHL, DEL/DHL had worse overall survival while DEL/non-DHL did not significantly differ in overall …

Gut Oncomicrobiome Signatures (Goms) As Next-Generation Biomarkers For Cancer Immunotherapy, Andrew Maltez Thomas, Marine Fidelle, Bertrand Routy, Guido Kroemer, Jennifer A Wargo, Nicola Segata, Laurence Zitvogel

Faculty, Staff and Student Publications

Oncogenesis is associated with intestinal dysbiosis, and stool shotgun metagenomic sequencing in individuals with this condition might constitute a non-invasive approach for the early diagnosis of several cancer types. The prognostic relevance of antibiotic intake and gut microbiota composition urged investigators to develop tools for the detection of intestinal dysbiosis to enable patient stratification and microbiota-centred clinical interventions. Moreover, since the advent of immune-checkpoint inhibitors (ICIs) in oncology, the identification of biomarkers for predicting their efficacy before starting treatment has been an unmet medical need. Many previous studies addressing this question, including a meta-analysis described herein, have led to the …

Efficacy Of Immune Checkpoint Inhibitors For The Treatment Of Advanced Melanoma In Patients With Concomitant Chronic Lymphocytic Leukemia, S H Cass, J W D Tobin, Y D Seo, G Gener-Ricos, E Z Keung, E M Burton, M A Davies, J L Mcquade, A J Lazar, R Mason, M Millward, S Sandhu, C Khoo, L Warburton, V Guerra, A Haydon, H Dearden, A M Menzies, M S Carlino, J L Smith, P Mollee, M Burgess, S Mapp, C Keane, V Atkinson, S A Parikh, S N Markovic, W Ding, T G Call, P J Hampel, G V Long, J A Wargo, A Ferrajoli

Faculty, Staff and Student Publications

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the management of advanced melanoma (AM). However, data on ICI effectiveness have largely been restricted to clinical trials, thereby excluding patients with co-existing malignancies. Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia and is associated with increased risk of melanoma. CLL alters systemic immunity and can induce T-cell exhaustion, which may limit the efficacy of ICIs in patients with CLL. We, therefore, sought to examine the efficacy of ICI in patients with these co-occurring diagnoses.

PATIENTS AND METHODS: In this international multicenter study, a retrospective review of clinical databases identified patients …

Cell Entry And Release Of Quasi-Enveloped Human Hepatitis Viruses, Anshuman Das, Efraín E Rivera-Serrano, Xin Yin, Christopher M Walker, Zongdi Feng, Stanley M Lemon

Faculty, Staff and Student Publications

Infectious hepatitis type A and type E are caused by phylogenetically distinct single-stranded, positive-sense RNA viruses that were once considered to be non-enveloped. However, studies show that both are released nonlytically from hepatocytes as 'quasi-enveloped' virions cloaked in host membranes. These virion types predominate in the blood of infected individuals and mediate virus spread within the liver. They lack virally encoded proteins on their surface and are resistant to neutralizing anti-capsid antibodies induced by infection, yet they efficiently enter cells and initiate new rounds of virus replication. In this Review, we discuss the mechanisms by which specific peptide sequences in …