Medical Specialties Commons^™

Naive T Cells Inhibit The Outgrowth Of Intractable Antigen-Activated Memory T Cells: Implications For T-Cell Immunotherapy, Sandhya Sharma, Mae Woods, Naren U Mehta, Tim Sauer, Kathan S Parikh, Michael Schmuck-Henneresse, Huimin Zhang, Birju Mehta, Malcolm K Brenner, Helen E Heslop, Cliona M Rooney

Faculty, Staff and Students Publications

BACKGROUND: The wider application of T cells targeting viral tumor-antigens via their native receptors is hampered by the failure to expand potent tumor-specific T cells from patients. Here, we examine reasons for and solutions to this failure, taking as our model the preparation of Epstein-Barr virus (EBV)-specific T cells (EBVSTs) for the treatment of EBV-positive lymphoma. EBVSTs could not be manufactured from almost one-third of patients, either because they failed to expand, or they expanded, but lacked EBV specificity. We identified an underlying cause of this problem and established a clinically feasible approach to overcome it.

METHODS: CD45RO+CD45RA- memory compartment …

Contribution Of Adaptive Immunity To Human Copd And Experimental Models Of Emphysema, Farrah Kheradmand, Yun Zhang, David B Corry

Faculty, Staff and Students Publications

The pathophysiology of chronic obstructive pulmonary disease (COPD) and the undisputed role of innate immune cells in this condition have dominated the field in the basic research arena for many years. Recently, however, compelling data suggesting that adaptive immune cells may also contribute to the progressive nature of lung destruction associated with COPD in smokers have gained considerable attention. The histopathological changes in the lungs of smokers can be limited to the large or small airways, but alveolar loss leading to emphysema, which occurs in some individuals, remains its most significant and irreversible outcome. Critically, however, the question of why …

Decs: A Tool For Systematic Cell Type Annotations Of Single-Cell Rna Sequencing Data Among Human Tissues, Guangsheng Pei, Fangfang Yan, Lukas M Simon, Yulin Dai, Peilin Jia, Zhongming Zhao

Faculty, Staff and Student Publications

Single-cell RNA sequencing (scRNA-seq) is revolutionizing the study of complex and dynamic cellular mechanisms. However, cell type annotation remains a main challenge as it largely relies on a priori knowledge and manual curation, which is cumbersome and subjective. The increasing number of scRNA-seq datasets, as well as numerous published genetic studies, has motivated us to build a comprehensive human cell type reference atlas.Here, we present decoding Cell type Specificity (deCS), an automatic cell type annotation method augmented by a comprehensive collection of human cell type expression profiles and marker genes. We used deCS to annotate scRNA-seq data from various tissue …

Addressing The Surgical Workplace: An Opportunity To Create A Culture Of Belonging, Carla M. Pugh, Orlando C. Kirton, J. E. Betsy Tuttle, Ronald V. Maier, Yue-Yung Hu, John H. Stewart, Julie Ann Freischlag, Julie Ann Sosa, Selwyn M Vickers, Mary T. Hawn, Timothy J. Eberlein, Diana L. Farmer, Robert S. Higgins, Carlos A. Pellegrini, Sanziana A. Roman, Marie L. Crandall, Christian M. De Virgilio, Allan Tsung, L. D. Britt

Abington Jefferson Health Papers

No abstract provided.

Necrotizing Enterocolitis In Premature Infants-A Defect In The Brakes? Evidence From Clinical And Animal Studies., Venkatesh Sampath, Maribel Martinez, Michael Caplan, Mark A. Underwood, Alain Cuna

Manuscripts, Articles, Book Chapters and Other Papers

A key aspect of postnatal intestinal adaptation is the establishment of symbiotic relationships with co-evolved gut microbiota. Necrotizing enterocolitis (NEC) is the most severe disease arising from failure in postnatal gut adaptation in premature infants. Although pathological activation of intestinal Toll-like receptors (TLRs) is believed to underpin NEC pathogenesis, the mechanisms are incompletely understood. We postulate that unregulated aberrant TLR activation in NEC arises from a failure in intestinal-specific mechanisms that tamponade TLR signaling (the brakes). In this review, we discussed the human and animal studies that elucidate the developmental mechanisms inhibiting TLR signaling in the postnatal intestine (establishing the …

Optimized Acute Treatment Of Migraine Is Associated With Greater Productivity In People With Migraine: Results From The Chronic Migraine Epidemiology And Outcomes (Cameo) Study., Dawn C Buse, Stephanie J. Nahas, Walter Buzz F Stewart, Cynthia E Armand, Michael L Reed, Kristina M Fanning, Aubrey Manack Adams, Richard B Lipton

Department of Neurology Faculty Papers

OBJECTIVE: This study aimed to ascertain whether level of optimization of acute treatment of migraine is related to work productivity across the spectrum of migraine.

METHODS: Data were from the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study, an internet-based longitudinal survey. Respondents with migraine who reported full-time employment and use of ≥1 acute prescription medication for migraine were included. We determined relationships among lost productive time (LPT; measured with the Migraine Disability Assessment Scale), acute treatment optimization (Migraine Treatment Optimization Questionnaire- ), and monthly headache days (MHDs).

RESULTS: There was a direct relationship between LPT and MHD category. Greater acute …

Prehospital Shock Index Predicts Outcomes After Prolonged Transport: A Multicenter Rural Study., James M Bardes, Bradley S Price, Hannah Bailey, Alexander Quinn, Zachary D Warriner, Andrew C Bernard, Aimee Lariccia, M Chance Spalding, Melissa B Linskey Dougherty, Scott B Armen, Alison Wilson

Trauma and Acute Care Articles

BACKGROUND: Shock index (SI) predicts outcomes after trauma. Prior single-center work demonstrated that emergency medical services (EMSs) initial SI was the most accurate predictor of hospital outcomes in a rural environment. This study aimed to evaluate the predictive ability of SI in multiple rural trauma systems with prolonged transport times to a definitive care facility.

METHODS: This retrospective review was performed at four American College of Surgeons-verified level 1 trauma centers with large rural catchment basins. Adult trauma patients who were transferred and arrived >60 minutes from scene during 2018 were included. Patients who sustained blunt chest or abdominal trauma …

An Untrained Deep Learning Method For Reconstructing Dynamic Mr Images From Accelerated Model-Based Data, Kalina P Slavkova, Julie C Dicarlo, Viraj Wadhwa, Sidharth Kumar, Chengyue Wu, John Virostko, Thomas E Yankeelov, Jonathan I Tamir

Faculty, Staff and Student Publications

PURPOSE: To implement physics-based regularization as a stopping condition in tuning an untrained deep neural network for reconstructing MR images from accelerated data.

METHODS: The ConvDecoder (CD) neural network was trained with a physics-based regularization term incorporating the spoiled gradient echo equation that describes variable-flip angle data. Fully-sampled variable-flip angle k-space data were retrospectively accelerated by factors of R = {8, 12, 18, 36} and reconstructed with CD, CD with the proposed regularization (CD + r), locally low-rank (LR) reconstruction, and compressed sensing with L1-wavelet regularization (L1). Final images from CD + r training were evaluated at the "argmin" of …

Causal Effects On Complex Traits Are Similar For Common Variants Across Segments Of Different Continental Ancestries Within Admixed Individuals, Kangcheng Hou, Yi Ding, Ziqi Xu, Yue Wu, Arjun Bhattacharya, Rachel Mester, Gillian M Belbin, Steve Buyske, David V Conti, Burcu F Darst, Myriam Fornage, Chris Gignoux, Xiuqing Guo, Christopher Haiman, Eimear E Kenny, Michelle Kim, Charles Kooperberg, Leslie Lange, Ani Manichaikul, Kari E North, Ulrike Peters, Laura J Rasmussen-Torvik, Stephen S Rich, Jerome I Rotter, Heather E Wheeler, Genevieve L Wojcik, Ying Zhou, Sriram Sankararaman, Bogdan Pasaniuc

Faculty, Staff and Student Publications

Individuals of admixed ancestries (for example, African Americans) inherit a mosaic of ancestry segments (local ancestry) originating from multiple continental ancestral populations. This offers the unique opportunity of investigating the similarity of genetic effects on traits across ancestries within the same population. Here we introduce an approach to estimate correlation of causal genetic effects (radmix) across local ancestries and analyze 38 complex traits in African-European admixed individuals (N = 53,001) to observe very high correlations (meta-analysis radmix = 0.95, 95% credible interval 0.93-0.97), much higher than correlation of causal effects across continental ancestries. We replicate our results using regression-based methods …

Consensus-Based Evaluation Of Outcome Measures In Pediatric Stroke Care: A Toolkit, Samantha J Feldman, Lauren A Beslow, Ryan J Felling, Laura A Malone, Michaela Waak, Stuart Fraser, Nihal Bakeer, Jo Ellen M Lee, Victoria Sherman, Melissa M Howard, Beth Anne Cavanaugh, Robyn Westmacott, Lori C Jordan

Faculty, Staff and Student Publications

Following a pediatric stroke, outcome measures selected for monitoring functional recovery and development vary widely. We sought to develop a toolkit of outcome measures that are currently available to clinicians, possess strong psychometric properties, and are feasible for use within clinical settings. A multidisciplinary group of clinicians and scientists from the International Pediatric Stroke Organization comprehensively reviewed the quality of measures in multiple domains described in pediatric stroke populations including global performance, motor and cognitive function, language, quality of life, and behavior and adaptive functioning. The quality of each measure was evaluated using guidelines focused on responsiveness and sensitivity, reliability, …

Quantification Of The Role Of Lead Foil In Flattening Filter Free Beam Reference Dosimetry, Song Gao, Christopher Nelson, Congjun Wang, Vindu Kathriarachchi, Michael Choi, Rishik Saxena, Robin Kendall, Peter Balter

Faculty, Staff and Student Publications

PURPOSE: To quantify the potential error in outputs for flattening filter free (FFF) beams associated with use of a lead foil in beam quality determination per the addendum protocol for TG-51, we examined differences in measurements of the beam quality conversion factor k

METHODS: Two FFF beams, a 6 MV FFF and a 10 MV FFF, were calibrated on eight Varian TrueBeams and two Elekta Versa HD linear accelerators (linacs) according to the TG-51 addendum protocol by using Farmer ionization chambers [TN 30013 (PTW) and SNC600c (Sun Nuclear)] with traceable absorbed dose-to-water calibrations. In determining k

RESULTS: Differences in %dd(10)x …

Model-Constrained Reconstruction Accelerated With Fourier-Based Undersampling For Hyperpolarized [1-13c] Pyruvate Imaging, Zhan Xu, Keith A Michel, Christopher M Walker, Collin J Harlan, Gary V Martinez, Jeremy W Gordon, Hsin-Yu Chen, Daniel B Vigneron, James A Bankson

Faculty, Staff and Student Publications

PURPOSE: Model-constrained reconstruction with Fourier-based undersampling (MoReFUn) is introduced to accelerate the acquisition of dynamic MRI using hyperpolarized [1-

METHODS: The MoReFUn method resolves spatial aliasing using constraints introduced by a pharmacokinetic model that describes the signal evolution of both pyruvate and lactate. Acceleration was evaluated on three single-channel data sets: a numerical digital phantom that is used to validate the accuracy of reconstruction and model parameter restoration under various SNR and undersampling ratios, prospectively and retrospectively sampled data of an in vitro dynamic multispectral phantom, and retrospectively undersampled imaging data from a prostate cancer patient to test the fidelity …

Enoxaparin May Be Associated With Lower Rates Of Mortality Than Unfractionated Heparin In Neurocritical And Surgical Patients, Sophie Samuel, Catherine To, Yaobin Ling, Kai Zhang, Xiaoqian Jiang, Elmer V Bernstam

Faculty, Staff and Student Publications

Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are often administered to prevent venous thromboembolism (VTE) in critically ill patients. However, the preferred prophylactic agent (UFH or LMWH) is not known. We compared the all-cause mortality rate in patients receiving UFH to LMWH for VTE prophylaxis. We conducted a retrospective propensity score adjusted analysis of patients admitted to neuro-critical, surgical, or medical intensive care units. Patients were included if they were screened with venous duplex ultrasonography or computed tomography angiography for detection of VTE. The primary outcome was all-cause mortality. Secondary outcomes included the prevalence of VTE, deep vein …

Renal-Hepatic-Pancreatic Dysplasia Type 2: Perinatal Lethal Condition Or A Multisystemic Disorder With Variable Expressivity, Kathryn Gunther, Essam M Imseis, Joyce P Samuel, Elizabeth A Hillman, Tiina H Ojala, Timo Jahnukainen, Paul R Hillman

Faculty, Staff and Student Publications

BACKGROUND: Renal-hepatic-pancreatic dysplasia type 2 (RHPD2) is a rare condition that has been described in the literature disproportionately in perinatal losses. The main features of liver and kidney involvement are well described, with cardiac malformations and cardiomyopathy adding additional variation to the phenotype. Many patients reported are within larger cohorts of congenital anomalies of kidney and urinary tract (CAKUT) or liver failure, and with minimal phenotypic and clinical course data.

METHODS: An independent series of phenotypes and prognosis was aggregated from the literature. In this literature review, we describe an additional patient with RHPD2, provide a clinical update on the …

Institutional Strategies To Maintain And Grow Imaging Research During The Covid-19 Pandemic, Mai-Lan Ho, Corey W Arnold, Summer J Decker, John D Hazle, Elizabeth A Krupinski, David A Mankoff

Faculty, Staff and Student Publications

Understanding imaging research experiences, challenges, and strategies for academic radiology departments during and after COVID-19 is critical to prepare for future disruptive events. We summarize key insights and programmatic initiatives at major academic hospitals across the world, based on literature review and meetings of the Radiological Society of North America Vice Chairs of Research (RSNA VCR) group. Through expert discussion and case studies, we provide suggested guidelines to maintain and grow radiology research in the postpandemic era.

Surgery After Braf-Directed Therapy Is Associated With Improved Survival In Brafv600e Mutant Anaplastic Thyroid Cancer: A Single-Center Retrospective Cohort Study, Xiao Zhao, Jennifer Rui Wang, Ramona Dadu, Naifa Lamki Busaidy, Lei Xu, Kim O Learned, Noah N Chasen, Thinh Vu, Anastasios Maniakas, Arturo A Eguia, Julia Diersing, Neil D Gross, Ryan Goepfert, Stephen Y Lai, Marie-Claude Hofmann, Renata Ferrarotto, Charles Lu, Gary Brandon Gunn, Michael T Spiotto, Vivek Subbiah, Michelle D Williams, Maria E Cabanillas, Mark E Zafereo

Faculty, Staff and Student Publications

Background: The aim of this study was to describe the oncologic outcomes of patients with BRAFV600E-mutated anaplastic thyroid cancer (ATC) who had neoadjuvant BRAF-directed therapy with subsequent surgery. For context, we also reviewed patients who received BRAF-directed therapy after surgery, and those who did not have surgery after BRAF-directed therapy.

Methods: This was a single-center retrospective cohort study conducted at a tertiary care cancer center in Texas from 2017 to 2021. Fifty-seven consecutive patients with BRAFV600E-mutated ATC and at least 1 month of BRAF-directed therapy were included. Primary outcomes were overall survival (OS) and progression-free survival (PFS).

Results: All patients …

Hyperphosphorylated Tau In Mesial Temporal Lobe Epilepsy: A Neuropathological And Cognitive Study, Eliana C B Toscano, Érica L M Vieira, Lea T Grinberg, Natalia P Rocha, Joseane A S Brant, Regina S Paradela, Alexandre V Giannetti, Claudia K Suemoto, Renata E P Leite, Ricardo Nitrini, Milene A Rachid, Antonio L Teixeira

Faculty, Staff and Student Publications

Temporal lobe epilepsy (TLE) often courses with cognitive deficits, but its underlying neuronal basis remains unclear. Confluent data suggest that epilepsy share pathophysiological mechanisms with neurodegenerative diseases. However, as most studies analyze subjects 60 years old and older, it is challenging to rule out that neurodegenerative changes arise from age-related mechanisms rather than epilepsy in these individuals. To fill this gap, we conducted a neuropathological investigation of the hippocampal formation of 22 adults with mesial TLE and 20 age- and sex-matched controls (both younger than 60 years). Moreover, we interrogated the relationship between these neuropathological metrics and cognitive performance. Hippocampal …

Genomic-Transcriptomic Evolution In Lung Cancer And Metastasis, Carlos Martínez-Ruiz, James R M Black, Clare Puttick, Mark S Hill, Jonas Demeulemeester, Elizabeth Larose Cadieux, Kerstin Thol, Thomas P Jones, Selvaraju Veeriah, Cristina Naceur-Lombardelli, Antonia Toncheva, Paulina Prymas, Andrew Rowan, Sophia Ward, Laura Cubitt, Foteini Athanasopoulou, Oriol Pich, Takahiro Karasaki, David A Moore, Roberto Salgado, Emma Colliver, Carla Castignani, Michelle Dietzen, Ariana Huebner, Maise Al Bakir, Miljana Tanić, Thomas B K Watkins, Emilia L Lim, Ali M Al-Rashed, Danny Lang, James Clements, Daniel E Cook, Rachel Rosenthal, Gareth A Wilson, Alexander M Frankell, Sophie De Carné Trécesson, Philip East, Nnennaya Kanu, Kevin Litchfield, Nicolai J Birkbak, Allan Hackshaw, Stephan Beck, Peter Van Loo, Mariam Jamal-Hanjani, Charles Swanton, Nicholas Mcgranahan

Faculty, Staff and Student Publications

Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy1. Here, using paired whole-exome and RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell lung cancer tumours from 347 out of the first 421 patients prospectively recruited into the TRACERx study2,3. Analyses of 947 tumour regions, representing both primary and metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate the transcriptome as a major source of phenotypic variation. Gene expression levels and ITH relate to patterns of positive and negative selection during tumour evolution. We observe frequent copy number-independent allele-specific expression …

The Evolution Of Non-Small Cell Lung Cancer Metastases In Tracerx, Maise Al Bakir, Ariana Huebner, Carlos Martínez-Ruiz, Kristiana Grigoriadis, Thomas B K Watkins, Oriol Pich, David A Moore, Selvaraju Veeriah, Sophia Ward, Joanne Laycock, Diana Johnson, Andrew Rowan, Maryam Razaq, Mita Akther, Cristina Naceur-Lombardelli, Paulina Prymas, Antonia Toncheva, Sonya Hessey, Michelle Dietzen, Emma Colliver, Alexander M Frankell, Abigail Bunkum, Emilia L Lim, Takahiro Karasaki, Christopher Abbosh, Crispin T Hiley, Mark S Hill, Daniel E Cook, Gareth A Wilson, Roberto Salgado, Emma Nye, Richard Kevin Stone, Dean A Fennell, Gillian Price, Keith M Kerr, Babu Naidu, Gary Middleton, Yvonne Summers, Colin R Lindsay, Fiona H Blackhall, Judith Cave, Kevin G Blyth, Arjun Nair, Asia Ahmed, Magali N Taylor, Alexander James Procter, Mary Falzon, David Lawrence, Neal Navani, Ricky M Thakrar, Sam M Janes, Dionysis Papadatos-Pastos, Martin D Forster, Siow Ming Lee, Tanya Ahmad, Sergio A Quezada, Karl S Peggs, Peter Van Loo, Caroline Dive, Allan Hackshaw, Nicolai J Birkbak, Simone Zaccaria, Tracerx Consortium, Mariam Jamal-Hanjani, Nicholas Mcgranahan, Charles Swanton

Faculty, Staff and Student Publications

Metastatic disease is responsible for the majority of cancer-related deaths1. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% …

The Evolution Of Lung Cancer And Impact Of Subclonal Selection In Tracerx, Alexander M Frankell, Michelle Dietzen, Maise Al Bakir, Emilia L Lim, Takahiro Karasaki, Sophia Ward, Selvaraju Veeriah, Emma Colliver, Ariana Huebner, Abigail Bunkum, Mark S Hill, Kristiana Grigoriadis, David A Moore, James R M Black, Wing Kin Liu, Kerstin Thol, Oriol Pich, Thomas B K Watkins, Cristina Naceur-Lombardelli, Daniel E Cook, Roberto Salgado, Gareth A Wilson, Chris Bailey, Mihaela Angelova, Robert Bentham, Carlos Martínez-Ruiz, Christopher Abbosh, Andrew G Nicholson, John Le Quesne, Dhruva Biswas, Rachel Rosenthal, Clare Puttick, Sonya Hessey, Claudia Lee, Paulina Prymas, Antonia Toncheva, Jon Smith, Wei Xing, Jerome Nicod, Gillian Price, Keith M Kerr, Babu Naidu, Gary Middleton, Kevin G Blyth, Dean A Fennell, Martin D Forster, Siow Ming Lee, Mary Falzon, Madeleine Hewish, Michael J Shackcloth, Eric Lim, Sarah Benafif, Peter Russell, Ekaterini Boleti, Matthew G Krebs, Jason F Lester, Dionysis Papadatos-Pastos, Tanya Ahmad, Ricky M Thakrar, David Lawrence, Neal Navani, Sam M Janes, Caroline Dive, Fiona H Blackhall, Yvonne Summers, Judith Cave, Teresa Marafioti, Javier Herrero, Sergio A Quezada, Karl S Peggs, Roland F Schwarz, Peter Van Loo, Daniël M Miedema, Nicolai J Birkbak, Crispin T Hiley, Allan Hackshaw, Simone Zaccaria, Mariam Jamal-Hanjani, Nicholas Mcgranahan, Charles Swanton

Faculty, Staff and Student Publications

Lung cancer is the leading cause of cancer-associated mortality worldwide1. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) …

Evolutionary Characterization Of Lung Adenocarcinoma Morphology In Tracerx, Takahiro Karasaki, David A Moore, Selvaraju Veeriah, Cristina Naceur-Lombardelli, Antonia Toncheva, Neil Magno, Sophia Ward, Maise Al Bakir, Thomas B K Watkins, Kristiana Grigoriadis, Ariana Huebner, Mark S Hill, Alexander M Frankell, Christopher Abbosh, Clare Puttick, Haoran Zhai, Francisco Gimeno-Valiente, Sadegh Saghafinia, Nnennaya Kanu, Michelle Dietzen, Oriol Pich, Emilia L Lim, Carlos Martínez-Ruiz, James R M Black, Dhruva Biswas, Brittany B Campbell, Claudia Lee, Emma Colliver, Katey S S Enfield, Sonya Hessey, Crispin T Hiley, Simone Zaccaria, Kevin Litchfield, Nicolai J Birkbak, Elizabeth Larose Cadieux, Jonas Demeulemeester, Peter Van Loo, Prasad S Adusumilli, Kay See Tan, Waseem Cheema, Francisco Sanchez-Vega, David R Jones, Natasha Rekhtman, William D Travis, Allan Hackshaw, Teresa Marafioti, Roberto Salgado, John Le Quesne, Andrew G Nicholson, Tracerx Consortium, Nicholas Mcgranahan, Charles Swanton, Mariam Jamal-Hanjani

Faculty, Staff and Student Publications

Lung adenocarcinomas (LUADs) display a broad histological spectrum from low-grade lepidic tumors through to mid-grade acinar and papillary and high-grade solid, cribriform and micropapillary tumors. How morphology reflects tumor evolution and disease progression is poorly understood. Whole-exome sequencing data generated from 805 primary tumor regions and 121 paired metastatic samples across 248 LUADs from the TRACERx 421 cohort, together with RNA-sequencing data from 463 primary tumor regions, were integrated with detailed whole-tumor and regional histopathological analysis. Tumors with predominantly high-grade patterns showed increased chromosomal complexity, with higher burden of loss of heterozygosity and subclonal somatic copy number alterations. Individual regions …

Treatment Outcomes For Rheumatoid Arthritis-Associated Interstitial Lung Disease: A Real-World, Multisite Study Of The Impact Of Immunosuppression On Pulmonary Function Trajectory, Scott M Matson, Misbah Baqir, Teng Moua, Michael Marll, Jessica Kent, Nicholas S Iannazzo, Ryan D Boente, John M Donatelli, Junqiang Dai, Francisco J Diaz, M Kristen Demoruelle, Mark B Hamblin, Susan K Mathai, Jay H Ryu, Kristen Pope, Christopher M Walker, Joyce S Lee

Faculty, Staff and Student Publications

BACKGROUND: Rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) is common in patients with RA and leads to significant morbidity and mortality. No randomized, placebo-controlled data are available that support the role of immunosuppression to treat RA-associated ILD, despite being widely used in clinical practice.

RESEARCH QUESTION: How does immunosuppression impact pulmonary function trajectory in a multisite retrospective cohort of patients with RA-associated ILD?

STUDY DESIGN AND METHODS: Patients with RA who started treatment for ILD with mycophenolate, azathioprine, or rituximab were identified retrospectively from five ILD centers. Change in lung function before and after treatment was analyzed using a linear …

Autologous Stem Cell Transplantation For Patients With Multiple Myeloma With Translocation (4;14): The Md Anderson Cancer Center Experience, Oren Pasvolsky, Mahmoud R Gaballa, Denái R Milton, Adeel Masood, Sophiya S Sami, Mark R Tanner, Qaiser Bashir, Samer Srour, Neeraj Saini, Jeremy Ramdial, Yago Nieto, Guilin Tang, Pei Lin, Hans C Lee, Krina K Patel, Partow Kebriaei, Sheeba K Thomas, Donna M Weber, Robert Z Orlowski, Elizabeth J Shpall, Richard E Champlin, Muzaffar H Qazilbash

Faculty, Staff and Student Publications

Translocation between chromosomes 4 and 14, t(4;14), has been reported in 15% of patients with multiple myeloma (MM) and is considered a high-risk cytogenetic abnormality associated with inferior outcomes. Autologous hematopoietic stem cell transplantation (auto-HCT) is standard of care for patients with high-risk MM, yet there are scarce data on post-transplantation outcomes of patients with t(4;14) MM. The aim of the present study was to evaluate outcomes of MM patients with t(4;14) who underwent auto-HCT and received contemporary anti-myeloma agents for induction and post-transplantation maintenance. We conducted a retrospective analysis of MM patients with t(4;14), detected by fluorescence in situ …

Fear Of Recurrence, Emotional Well-Being And Quality Of Life Among Long-Term Advanced Ovarian Cancer Survivors, Kathryn Osann, Lari Wenzel, Chelsea Mckinney, Lynne Wagner, David Cella, Giulia Fulci, Mary J Scroggins, Heather A Lankes, Victoria Wang, Kenneth P Nephew, George L Maxwell, Samuel C Mok, Thomas P Conrads, Austin Miller, Michael Birrer

Faculty, Staff and Student Publications

OBJECTIVE: Although advanced stage epithelial ovarian cancer is widely considered life-threatening, 17% of women with advanced disease will survive long-term. Little is known about the health-related quality of life (QOL) of long-term ovarian cancer survivors, or how fear of recurrence might affect QOL.

METHODS: 58 long-term survivors with advanced disease participated in the study. Participants completed standardized questionnaires to capture cancer history, QOL, and fear of recurrent disease (FOR). Statistical analyses included multivariable linear models.

RESULTS: Participants averaged 52.8 years at diagnosis and had survived >8 years (mean:13.5); 64% had recurrent disease. Mean FACT-G, FACT-O, and FACT-O-TOI (TOI) scores were …

The Glycoprotein Cd147 Defines Mirna-Enriched Extracellular Vesicles That Derive From Cancer Cells, Song Yi Ko, Wonjae Lee, Melanie Weigert, Eric Jonasch, Ernst Lengyel, Honami Naora

Faculty, Staff and Student Publications

Extracellular vesicles (EVs) are ideal for liquid biopsy, but distinguishing cancer cell‐derived EVs and subpopulations of biomarker‐containing EVs in body fluids has been challenging. Here, we identified that the glycoproteins CD147 and CD98 define subpopulations of EVs that are distinct from classical tetraspanin+ EVs in their biogenesis. Notably, we identified that CD147+ EVs have substantially higher microRNA (miRNA) content than tetraspanin+ EVs and are selectively enriched in miRNA through the interaction of CD147 with heterogeneous nuclear ribonucleoprotein A2/B1. Studies using mouse xenograft models showed that CD147+ EVs predominantly derive from cancer cells, whereas the majority of tetraspanin+ EVs are not …

Emerging Role Of Tak1 In The Regulation Of Skeletal Muscle Mass, Anirban Roy, Vihang A Narkar, Ashok Kumar

Faculty, Staff and Student Publications

Maintenance of skeletal muscle mass and strength throughout life is crucial for heathy living and longevity. Several signaling pathways have been implicated in the regulation of skeletal muscle mass in adults. TGF-β-activated kinase 1 (TAK1) is a key protein, which coordinates the activation of multiple signaling pathways. Recently, it was discovered that TAK1 is essential for the maintenance of skeletal muscle mass and myofiber hypertrophy following mechanical overload. Forced activation of TAK1 in skeletal muscle causes hypertrophy and attenuates denervation-induced muscle atrophy. TAK1-mediated signaling in skeletal muscle promotes protein synthesis, redox homeostasis, mitochondrial health, and integrity of neuromuscular junctions. In …

Reflection Spectroscopy-Assessed Skin Carotenoids Are Sensitive To Change In Carotenoid Intake In A 6-Week Randomized Controlled Feeding Trial In A Racially/Ethnically Diverse Sample, Stephanie Jilcott Pitts, Nancy E Moran, Melissa N Laska, Qiang Wu, Lisa Harnack, Stacey Moe, Pamela Carr-Manthe, Elizabeth Gates, Jocelyn Chang, Yusuf Zaidi, Abigail Gelineau, Lauren Berg, Neal E Craft

Children’s Nutrition Research Center Staff Publications

Background: Reflection spectroscopy, utilized by the Veggie Meter, is a less-expensive, noninvasive method to quantify skin carotenoids and is a valid approximation of fruit and vegetable (FV) intake. However, it is unknown to what degree Veggie Meter-assessed skin carotenoid score change is responsive to changes in carotenoid intake.

Objectives: This study aimed to evaluate Veggie Meter-assessed skin carotenoid score response in a 6-wk randomized controlled trial of a carotenoid-containing juice to determine whether the Veggie Meter can be used to detect nutritionally relevant changes in carotenoid intake; and to compare skin and plasma carotenoid responses with the 6-wk trial.

Methods: …

Community Health Workers To Increase Cancer Screening: 3 Community Guide Systematic Reviews, Devon L Okasako-Schmucker, Yinan Peng, Jamaicia Cobb, Leigh R Buchanan, Ka Zang Xiong, Shawna L Mercer, Susan A Sabatino, Stephanie Melillo, Patrick L Remington, Shiriki K Kumanyika, Beth Glenn, Erica S Breslau, Cam Escoffery, Maria E Fernandez, Gloria D Coronado, Karen Glanz, Patricia D Mullen, Sally W Vernon

Faculty, Staff and Student Publications

INTRODUCTION: Many in the U.S. are not up to date with cancer screening. This systematic review examined the effectiveness of interventions engaging community health workers to increase breast, cervical, and colorectal cancer screening.

METHODS: Authors identified relevant publications from previous Community Guide systematic reviews of interventions to increase cancer screening (1966 through 2013) and from an update search (January 2014-November 2021). Studies written in English and published in peer-reviewed journals were included if they assessed interventions implemented in high-income countries; reported screening for breast, cervical, or colorectal cancer; and engaged community health workers to implement part or all of the …

Diet, Physical Activity, And Stress Among Wheelchair Users With Multiple Sclerosis: Examining Individual And Co-Occurring Behavioral Risk Factors, Stephanie L Silveira, Brenda Jeng, Gary Cutter, Robert W Motl

Faculty, Staff and Student Publications

OBJECTIVE: This study examined individual and co-occurring behavioral risk factors (diet, exercise, and stress) in wheelchair users with multiple sclerosis (MS) and potential association with MS symptoms (ie, fatigue, depression, anxiety, pain, sleep, and health-related quality of life [HRQOL]).

DESIGN: Survey.

SETTING: General Community.

PARTICIPANTS: One hundred twenty-three wheelchair users with MS completed this study (N=123).

INTERVENTIONS: Not applicable.

MAIN OUTCOME MEASURES: Participants were mailed instructions for accessing online questionnaires (demographic and clinical characteristics, Godin Leisure-Time Exercise Questionnaire, Perceived Stress Scale, Automated Self-Administered 24-Hour Dietary Assessment Tool, and MS symptoms).

RESULTS: Standard cut-points were used to categorize behavioral risk factors …

Accurate Detection Of Α-Synuclein Seeds In Cerebrospinal Fluid From Isolated Rapid Eye Movement Sleep Behavior Disorder And Patients With Parkinson's Disease In The Denovo Parkinson (Denopa) Cohort, Luis Concha-Marambio, Sandrina Weber, Carly M Farris, Mohammed Dakna, Elisabeth Lang, Tamara Wicke, Yihua Ma, Maritta Starke, Jens Ebentheuer, Friederike Sixel-Döring, Maria-Lucia Muntean, Sebastian Schade, Claudia Trenkwalder, Claudio Soto, Brit Mollenhauer

Faculty, Staff and Student Publications

BACKGROUND: Misfolded α-synuclein (αSyn) aggregates (αSyn-seeds) in cerebrospinal fluid (CSF) are biomarkers for synucleinopathies such as Parkinson's disease (PD). αSyn-seeds have been detected in prodromal cases with isolated rapid eye movement sleep behavior disorder (iRBD).

OBJECTIVES: The objective of this study was to determine the accuracy of the αSyn-seed amplification assay (αS-SAA) in a comprehensively characterized cohort with a high proportion of PD and iRBD CSF samples collected at baseline.

METHODS: We used a high-throughput αS-SAA to analyze 233 blinded CSF samples from 206 participants of the DeNovo Parkinson Cohort (DeNoPa) (113 de novo PD, 64 healthy controls, 29 iRBD …