Medical Specialties Commons^™

Comparative Analysis Of Dimension Reduction Methods For Cytometry By Time-Of-Flight Data, Kaiwen Wang, Yuqiu Yang, Fangjiang Wu, Bing Song, Xinlei Wang, Tao Wang

Faculty, Staff and Student Publications

While experimental and informatic techniques around single cell sequencing (scRNA-seq) are advanced, research around mass cytometry (CyTOF) data analysis has severely lagged behind. CyTOF data are notably different from scRNA-seq data in many aspects. This calls for the evaluation and development of computational methods specific for CyTOF data. Dimension reduction (DR) is one of the critical steps of single cell data analysis. Here, we benchmark the performances of 21 DR methods on 110 real and 425 synthetic CyTOF samples. We find that less well-known methods like SAUCIE, SQuaD-MDS, and scvis are the overall best performers. In particular, SAUCIE and scvis …

Emotional, Behavioral, And Physical Health Consequences Of Loneliness In Young Adult Survivors Of Childhood Cancer: Results From The Childhood Cancer Survivor Study, Chiara Papini, Ameera A Fayad, Mingjuan Wang, Fiona S M Schulte, I-Chan Huang, Yu-Ping Chang, Rebecca M Howell, Deokumar Srivastava, Wendy M Leisenring, Gregory T Armstrong, Todd M Gibson, Leslie L Robison, Kevin C Oeffinger, Kevin R Krull, Tara M Brinkman

Faculty, Staff and Student Publications

Background: Young adults in the general population are at risk of experiencing loneliness, which has been associated with physical and mental health morbidities. The prevalence and consequences of loneliness in young adult survivors of childhood cancer remain unknown.

Methods: A total of 9664 young adult survivors of childhood cancer (median age at diagnosis 10.5 years [interquartile range (IQR), 5-15], 27.1 years at baseline [IQR, 23-32]) and 2221 siblings enrolled in the Childhood Cancer Survivor Study completed a self-reported survey question assessing loneliness on the Brief Symptom Inventory-18 at baseline and follow-up (median follow-up, 6.6 years). Multivariable models evaluated the prevalence …

Integrated Pathologic Score Effectively Stratifies Patients With Pancreatic Ductal Adenocarcinoma Who Received Neoadjuvant Therapy And Pancreaticoduodenectomy, Aaron J Sohn, Mehran Taherian, Matthew H G Katz, Laura R Prakash, Deyali Chatterjee, Hua Wang, Michael Kim, Ching-Wei D Tzeng, Jeffrey E Lee, Naruhiko Ikoma, Asif Rashid, Robert A Wolff, Dan Zhao, Eugene J Koay, Ryan Sun, Anirban Maitra, Huamin Wang

Faculty, Staff and Student Publications

Neoadjuvant therapy is increasingly used to treat patients with pancreatic ductal adenocarcinoma (PDAC). Pathologic parameters of treated PDAC, including tumor (ypT) and lymph node (ypN) stage, and tumor response grading (TRG) are important prognostic factors in this group of patients. To our knowledge, a multifactorial prognostic score combining pathologic features including ypT, ypN, and TRG in treated PDAC patients has not been reported. Our cohort consisted of 398 PDAC patients who received neoadjuvant therapy and underwent pancreaticoduodenectomy at our institution. All pancreaticoduodenectomy specimens were grossly and microscopically evaluated using a standard protocol. The integrated pathologic score (IPS) was calculated as …

Data Partitioning And Statistical Considerations For Association Of Radiomic Features To Biological Underpinnings: What Is Needed, Michael A Jacobs

Faculty, Staff and Student Publications

No abstract provided.

Patient Radiation Doses In Interventional Radiology Procedures: Comparison Of Fluoroscopy Dose Indices Between The American College Of Radiology Dose Index Registry-Fluoroscopy Pilot And The Radiation Doses In Interventional Radiology Study, A Kyle Jones, Kevin A Wunderle, Tom Fruscello, Michael Simanowith, Brendan Cline, Shalmali Dharmadhikari, Xinhui Duan, Jeremy C Durack, David Hirschl, Don-Soo Kim, Usman Mahmood, Steve D Mann, Charles Martin, Zeyad Metwalli, Jeffrey M Moirano, Rebecca A Neill, Janice Newsome, Horacio Padua, Alan H Schoenfeld, Donald L Miller

Faculty, Staff and Student Publications

Purpose: To compare radiation dose index distributions for fluoroscopically guided interventions in interventional radiology from the American College of Radiology (ACR) Fluoroscopy Dose Index Registry (DIR-Fluoro) pilot to those from the Radiation Doses in Interventional Radiology (RAD-IR) study.

Materials and methods: Individual and grouped ACR Common identification numbers (procedure types) from the DIR-Fluoro pilot were matched to procedure types in the RAD-IR study. Fifteen comparisons were made. Distribution parameters, including the 10th, 25th, 50th, 75th, and 95th percentiles, were compared for fluoroscopy time (FT), cumulative air kerma (Ka,r), and kerma area product (PKA). Two derived indices were computed using median …

Patient Radiation Doses In Ir Procedures: The American College Of Radiology Dose Index Registry-Fluoroscopy Pilot, A Kyle Jones, Kevin A Wunderle, Tom Fruscello, Michael Simanowith, Brendan Cline, Shalmali Dharmadhikari, Xinhui Duan, Jeremy C Durack, David Hirschl, Don-Soo Kim, Usman Mahmood, Steve D Mann, Charles Martin, Zeyad Metwalli, Jeffrey M Moirano, Rebecca A Neill, Janice Newsome, Horacio Padua, Alan H Schoenfeld, Donald L Miller

Faculty, Staff and Student Publications

Purpose: To update normative data on fluoroscopy dose indices in the United States for the first time since the Radiation Doses in Interventional Radiology study in the late 1990s.

Materials and methods: The Dose Index Registry-Fluoroscopy pilot study collected data from March 2018 through December 2019, with 50 fluoroscopes from 10 sites submitting data. Primary radiation dose indices including fluoroscopy time (FT), cumulative air kerma (Ka,r), and kerma area product (PKA) were collected for interventional radiology fluoroscopically guided interventional (FGI) procedures. Clinical facility procedure names were mapped to the American College of Radiology (ACR) common procedure lexicon. Distribution parameters including …

Letter To The Editor: Quality Criteria For Computational Models Predicting Individual Outcomes In Car-T Cell Therapy, Anna M Mc Laughlin, Cassian Yee

Faculty, Staff and Student Publications

No abstract provided.

Long-Term Outcomes Of Allogeneic Hematopoietic Cell Transplantation In Patients With Newly Diagnosed Multiple Myeloma, Aimaz Afrough, Leonard C Alsfeld, Denái R Milton, Ruby Delgado, Uday R Popat, Yago Nieto, Partow Kebriaei, Betul Oran, Neeraj Saini, Samer Srour, Chitra Hosing, Faisal H Cheema, Sairah Ahmed, Elisabet E Manasanch, Hans C Lee, Gregory P Kaufman, Krina K Patel, Donna M Weber, Robert Z Orlowski, Chelsea C Pinnix, Bouthaina S Dabaja, Sheeba K Thomas, Richard E Champlin, Elizabeth J Shpall, Muzaffar H Qazilbash, Qaiser Bashir

Faculty, Staff and Student Publications

Despite remarkable progress in survival with the availability of novel agents, an overwhelming majority of patients with multiple myeloma (MM) have disease that relapses. Allogeneic (allo-) hematopoietic cell transplantation (HCT) is a potentially curative option for a subgroup of patients with high-risk MM. This study assessed the long-term outcome of MM patients who underwent allo-HCT while in first remission as consolidation treatment. Thirty-three patients with newly diagnosed MM who underwent allo-HCT as part of consolidation therapy between 1994 and 2016 were reviewed retrospectively. Of these patients, 70% underwent autologous HCT before allo-HCT. All patients were chemosensitive and achieved at least …

Quality Assurance Assessment Of Intra-Acquisition Diffusion-Weighted And T2-Weighted Magnetic Resonance Imaging Registration And Contour Propagation For Head And Neck Cancer Radiotherapy, Mohamed A Naser, Kareem A Wahid, Sara Ahmed, Vivian Salama, Cem Dede, Benjamin W Edwards, Ruitao Lin, Brigid Mcdonald, Travis C Salzillo, Renjie He, Yao Ding, Moamen Abobakr Abdelaal, Daniel Thill, Nicolette O'Connell, Virgil Willcut, John P Christodouleas, Stephen Y Lai, Clifton D Fuller, Abdallah S R Mohamed

Faculty, Staff and Student Publications

BACKGROUND/PURPOSE: Adequate image registration of anatomical and functional magnetic resonance imaging (MRI) scans is necessary for MR-guided head and neck cancer (HNC) adaptive radiotherapy planning. Despite the quantitative capabilities of diffusion-weighted imaging (DWI) MRI for treatment plan adaptation, geometric distortion remains a considerable limitation. Therefore, we systematically investigated various deformable image registration (DIR) methods to co-register DWI and T2-weighted (T2W) images.

MATERIALS/METHODS: We compared three commercial (ADMIRE, Velocity, Raystation) and three open-source (Elastix with default settings [Elastix Default], Elastix with parameter set 23 [Elastix 23], Demons) post-acquisition DIR methods applied to T2W and DWI MRI images acquired during the same …

Effect Of The Physical Fibrillated Sweet Potato (Ipomoea Batatas) Stem On The Plant-Based Patty Analogues, Suyoon Lee, You Young Lee, Yang Kim, Seung Hwan Ham, Min Gyu Lee, Jungwoo Hahn, Young Jin Choi

Faculty, Staff and Student Publications

In this study, a dietary fiber extracted from sweet potato stems (Ipomoea batatas, PS) was evaluated for its ability to improve the quality of vegetable patty analogues. A patty analogues containing 0–50 wt% dietary fiber were prepared to analyze the utilized dietary fiber's performance. To evaluate the manufactured patty analogues, texture profile analysis, color analysis, emulsion stability, and microstructural analysis were conducted. As the PS increased, the hardness decreased, while the total expressible fluids tended to increase. The color analysis revealed that the a* value, which represents red, declined as the PS content increased, and heterogeneous colors showed …

Covid-19 And Employee Job Performance Trajectories: The Moderating Effect Of Different Sources Of Status, Xin Liu, Xiaoming Zheng, Byron Y Lee, Yu Yu, Mengyi Zhang

Faculty, Staff and Student Publications

This study investigates the impact of the COVID-19 pandemic on employee job performance trajectories, and further examines the moderating effects of different sources of status. Drawing from event system theory (EST), we propose that employee job performance decreases upon COVID-19 onset, but gradually increases during the postonset period. Furthermore, we argue that status from society, occupation, and workplace functions to moderate such performance trajectories. We test our hypotheses with a unique dataset of 708 employees that combines survey responses and job performance archival data over 21 consecutive months (10,808 observations) spanning the preonset, onset, and postonset periods of the initial …

Prediction Of Survival With Lower Intensity Therapy Among Older Patients With Acute Myeloid Leukemia, Koji Sasaki, Farhad Ravandi, Tapan M Kadia, Gautam Borthakur, Nicholas J Short, Nitin Jain, Naval G Daver, Elias J Jabbour, Guillermo Garcia-Manero, Sanam Loghavi, Keyur P Patel, Guillermo Montalban-Bravo, Lucia Masarova, Courtney D Dinardo, Hagop M Kantarjian

Faculty, Staff and Student Publications

BACKGROUND: The aim of this study was to develop a prognostic model for survival in older/unfit patients with newly diagnosed acute myeloid leukemia (AML) who were treated with lower-intensity chemotherapy regimens.

METHODS: The authors reviewed all older/unfit patients with newly diagnosed AML who received lower-intensity chemotherapy from 2000 until 2020 at their institution. A total of 1462 patients were included. They were divided (3:1 basis) into a training (n = 1088) and a validation group (n = 374).

RESULTS: In the training cohort of 1088 patients (median age, 72 years), the multivariate analysis identified 11 consistent independent adverse factors associated …

The Outcomes Of Patients With Chronic Myeloid Leukemia Treated With Third-Line Bcr::Abl1 Tyrosine Kinase Inhibitors, Elias J Jabbour, Koji Sasaki, Fadi G Haddad, Ghayas C Issa, Guillermo Garcia-Manero, Tapan M Kadia, Nitin Jain, Musa Yilmaz, Courtney D Dinardo, Keyur P Patel, Rashmi Kanagal-Shamanna, Richard Champlin, Issa F Khouri, Sara Dellasala, Sherry A Pierce, Hagop Kantarjian

Faculty, Staff and Student Publications

The BCR::ABL1 tyrosine kinase inhibitors (TKIs) have improved the outcomes of patients with chronic myeloid leukemia (CML). After failing second-generation TKI (2G-TKI), the optimal third-line therapy in chronic phase CML (CML-CP) is not well established. We analyzed 354 patients with CML-CP treated with a third-line BCR::ABL1 TKI at our institution, and in the PACE and OPTIC trials, and evaluated the outcome after alternate 2G-TKIs or ponatinib. We performed a propensity score matching analysis to compare outcomes and multivariate analysis to identify variables associated with survival. One hundred seventy-three (49%) patients received 2G-TKIs and 181 (51%) ponatinib. Patients in the ponatinib …

Tissue Specificity And Spatio-Temporal Dynamics Of The P53 Transcriptional Program, Vinod Pant, Chang Sun, Guillermina Lozano

Faculty, Staff and Student Publications

Transcription factors regulate hundreds of genes and p53 is no exception. As a stress responsive protein, p53 transactivates an array of downstream targets which define its role in maintaining physiological functions of cells/tissues. Despite decades of studies, our understanding of the p53 in vivo transcriptional program is still incomplete. Here we discuss some of the physiological stressors that activate p53, the pathological and physiological implications of p53 activation and the molecular profiling of the p53 transcriptional program in maintaining tissue homeostasis. We argue that the p53 transcriptional program is spatiotemporally regulated in a tissue-specific manner and define a p53 target …

A Non-Antibiotic-Disrupted Gut Microbiome Is Associated With Clinical Responses To Cd19-Car-T Cell Cancer Immunotherapy, Christoph K Stein-Thoeringer, Neeraj Y Saini, Eli Zamir, Viktoria Blumenberg, Maria-Luisa Schubert, Uria Mor, Matthias A Fante, Sabine Schmidt, Eiko Hayase, Tomo Hayase, Roman Rohrbach, Chia-Chi Chang, Lauren Mcdaniel, Ivonne Flores, Rogier Gaiser, Matthias Edinger, Daniel Wolff, Martin Heidenreich, Paolo Strati, Ranjit Nair, Dai Chihara, Luis E Fayad, Sairah Ahmed, Swaminathan P Iyer, Raphael E Steiner, Preetesh Jain, Loretta J Nastoupil, Jason Westin, Reetakshi Arora, Michael L Wang, Joel Turner, Meghan Menges, Melanie Hidalgo-Vargas, Kayla Reid, Peter Dreger, Anita Schmitt, Carsten Müller-Tidow, Frederick L Locke, Marco L Davila, Richard E Champlin, Christopher R Flowers, Elizabeth J Shpall, Hendrik Poeck, Sattva S Neelapu, Michael Schmitt, Marion Subklewe, Michael D Jain, Robert R Jenq, Eran Elinav

Faculty, Staff and Student Publications

Increasing evidence suggests that the gut microbiome may modulate the efficacy of cancer immunotherapy. In a B cell lymphoma patient cohort from five centers in Germany and the United States (Germany, n = 66; United States, n = 106; total, n = 172), we demonstrate that wide-spectrum antibiotics treatment ('high-risk antibiotics') prior to CD19-targeted chimeric antigen receptor (CAR)-T cell therapy is associated with adverse outcomes, but this effect is likely to be confounded by an increased pretreatment tumor burden and systemic inflammation in patients pretreated with high-risk antibiotics. To resolve this confounding effect and gain insights into antibiotics-masked microbiome signals …

Comparative Analysis Of Opioid Use Between Robotic And Open Pancreatoduodenectomy, Russell G Witt, Yuki Hirata, Laura R Prakash, Timothy E Newhook, Jessica E Maxwell, Michael P Kim, Hop S Tran Cao, Jeffrey E Lee, Jean-Nicolas Vauthey, Matthew H G Katz, Ching-Wei D Tzeng, Naruhiko Ikoma

Faculty, Staff and Student Publications

BACKGROUND/PURPOSE: Risk-stratified pancreatectomy clinical pathways using regional anesthesia and multimodality analgesia have decreased overall opioid use, but the additional benefits of robotic surgery in opioid reduction for pancreatoduodenectomy (PD) are unknown. We compared the inpatient opioid use between robotic PD and open PD.

METHODS: Patients undergoing open PD within a protocol evaluating preincisional regional anesthetic block bundles were compared to consecutively-treated patients undergoing robotic PD identified from a prospectively maintained single-institutional database. Clinical characteristics, operative outcomes, pain scores and inpatient oral morphine equivalent (OME) use were compared between patients treated with robotic or open PD. Patients with a history of …

Five-Year Survivors From Brain Metastases Treated With Stereotactic Radiosurgery: Biology, Improving Treatments, Or Just Plain Luck?, Jane B Pearce, Fang-Chi Hsu, Claire M Lanier, Christina K Cramer, Jimmy Ruiz, Hui-Wen Lo, Fei Xing, Margaret Smith, Wencheng Li, Christopher Whitlow, Jaclyn J White, Stephen B Tatter, Adrian W Laxton, Michael D Chan

Faculty, Staff and Student Publications

BACKGROUND: Improvements in therapies have led to an increasing number of long-term survivors of brain metastases. The present series compares a population of 5-year survivors of brain metastases to a generalized brain metastases population to assess for factors attributable to long-term survival.

METHODS: A single institution retrospective review was performed to identify 5-year survivors of brain metastases who received stereotactic radiosurgery (SRS). A historical control population of 737 patients with brain metastases was used to assess similarities and differences between the long-term survivor population and the general population treated with SRS.

RESULTS: A total of 98 patients with brain metastases …

Advancing Car T Cell Therapy Through The Use Of Multidimensional Omics Data, Jingwen Yang, Yamei Chen, Ying Jing, Michael R Green, Leng Han

Faculty, Staff and Student Publications

Despite the notable success of chimeric antigen receptor (CAR) T cell therapies in the treatment of certain haematological malignancies, challenges remain in optimizing CAR designs and cell products, improving response rates, extending the durability of remissions, reducing toxicity and broadening the utility of this therapeutic modality to other cancer types. Data from multidimensional omics analyses, including genomics, epigenomics, transcriptomics, T cell receptor-repertoire profiling, proteomics, metabolomics and/or microbiomics, provide unique opportunities to dissect the complex and dynamic multifactorial phenotypes, processes and responses of CAR T cells as well as to discover novel tumour targets and pathways of resistance. In this Review, …

Integrated Analysis Of Racial Disparities In Genomic Architecture Identifies A Trans-Ancestry Prognostic Subtype In Bladder Cancer, Baifeng Zhang, Peilin Jia, Jiayin Wang, Guangsheng Pei, Changxi Wang, Shimei Pei, Xiangchun Li, Zhongming Zhao, Xin Yi, Xin-Yuan Guan, Yi Huang

Faculty, Staff and Student Publications

The incidence of bladder cancer and patient survival vary greatly among different populations, but the influence of the associated molecular features and evolutionary processes on its clinical treatment and prognostication remains unknown. Here, we analyze the genomic architectures of 505 bladder cancer patients from Asian/Black/White populations. We identify a previously unknown association between AHNAK mutations and activity of the APOBEC-a mutational signature, the activity of which varied substantially across populations. All significantly mutated genes but only half of arm-level somatic copy number alterations (SCNAs) are enriched with clonal events, indicating large-scale SCNAs as rich sources of bladder cancer clonal diversities. …

Clinical Outcomes Of Immune Checkpoint Inhibitor Diabetes Mellitus At A Comprehensive Cancer Center, Rebecca Jeun, Priyanka C Iyer, Conor Best, Victor Lavis, Jeena M Varghese, Sireesha Yedururi, Veronica Brady, Isabella C Glitza Oliva, Ramona Dadu, Denai R Milton, Kristy Brock, Sonali Thosani

Faculty, Staff and Student Publications

Introduction: Immune checkpoint inhibitor-associated diabetes mellitus (ICI-DM) is a rare adverse event. In this study, we characterize clinical outcomes of patients with ICI-DM and evaluate survival impact of this complication on melanoma patients.

Research design & methods: We conducted a retrospective review of 76 patients diagnosed with ICI-DM from April 2014 to December 2020.

Results: 68% of patients presented in diabetic ketoacidosis, 16% had readmissions for hyperglycemia, and hypoglycemia occurred in 70% of patients after diagnosis. Development of ICI-DM did not impact overall survival or progression-free survival in melanoma patients.

Conclusion: Development of ICI-DM is associated with long-term insulin dependence …

Axicabtagene Ciloleucel In Relapsed Or Refractory Large B-Cell Lymphoma Patients In Complete Metabolic Response, Andrew P Jallouk, Sushanth Gouni, Jason Westin, Lei Feng, Haleigh Mistry, Raphael E Steiner, Jinsu James, Mansoor Noorani, Sandra Horowitz, Nahum Puebla-Osorio, Luis E Fayad, Swaminathan P Iyer, Misha Hawkins, Christopher R Flowers, Sairah Ahmed, Loretta J Nastoupil, Partow Kebriaei, Elizabeth J Shpall, Sattva S Neelapu, Yago Nieto, Paolo Strati

Faculty, Staff and Student Publications

No abstract provided.

Inconsistent Partitioning And Unproductive Feature Associations Yield Idealized Radiomic Models, Mishka Gidwani, Ken Chang, Jay Biren Patel, Katharina Viktoria Hoebel, Syed Rakin Ahmed, Praveer Singh, Clifton David Fuller, Jayashree Kalpathy-Cramer

Faculty, Staff and Student Publications

Background Radiomics is the extraction of predefined mathematic features from medical images for the prediction of variables of clinical interest. While some studies report superlative accuracy of radiomic machine learning (ML) models, the published methodology is often incomplete, and the results are rarely validated in external testing data sets. Purpose To characterize the type, prevalence, and statistical impact of methodologic errors present in radiomic ML studies. Materials and Methods Radiomic ML publications were reviewed for the presence of performance-inflating methodologic flaws. Common flaws were subsequently reproduced with randomly generated features interpolated from publicly available radiomic data sets to demonstrate the …

Ablative Margins Of Colorectal Liver Metastases Using Deformable Ct Image Registration And Autosegmentation, Yuan-Mao Lin, Iwan Paolucci, Caleb S O'Connor, Brian M Anderson, Bastien Rigaud, Bryan M Fellman, Kyle A Jones, Kristy K Brock, Bruno C Odisio

Faculty, Staff and Student Publications

Background

Confirming ablation completeness with sufficient ablative margin is critical for local tumor control following colorectal liver metastasis (CLM) ablation. An image-based confirmation method considering patient- and ablation-related biomechanical deformation is an unmet need.

Purpose

To evaluate a biomechanical deformable image registration (DIR) method for three-dimensional (3D) minimal ablative margin (MAM) quantification and the association with local disease progression following CT-guided CLM ablation.

Materials and Methods

This single-institution retrospective study included patients with CLM treated with CT-guided microwave or radiofrequency ablation from October 2015 to March 2020. A biomechanical DIR method with AI-based autosegmentation of liver, tumors, and ablation zones …

A Deep-Learning-Based Dose Verification Tool Utilizing Fluence Maps For A Cobalt-60 Compensator-Based Intensity-Modulated Radiation Therapy System, Kyuhak Oh, Mary P Gronberg, Tucker J Netherton, Bishwambhar Sengupta, Carlos E Cardenas, Laurence E Court, Eric C Ford

Faculty, Staff and Student Publications

Background and purpose: A novel cobalt-60 compensator-based intensity-modulated radiation therapy (IMRT) system was developed for a resource-limited environment but lacked an efficient dose verification algorithm. The aim of this study was to develop a deep-learning-based dose verification algorithm for accurate and rapid dose predictions.

Materials and methods: A deep-learning network was employed to predict the doses from static fields related to beam commissioning. Inputs were a cube-shaped phantom, a beam binary mask, and an intersecting volume of the phantom and beam binary mask, while output was a 3-dimensional (3D) dose. The same network was extended to predict patient-specific doses for …

Molecular Function And Contribution Of Tbx4 In Development And Disease, Justyna A Karolak, Carrie L Welch, Christian Mosimann, Katarzyna Bzdęga, James D West, David Montani, Mélanie Eyries, Mary P Mullen, Steven H Abman, Matina Prapa, Stefan Gräf, Nicholas W Morrell, Anna R Hemnes, Frédéric Perros, Rizwan Hamid, Malcolm P O Logan, Jeffrey Whitsett, Csaba Galambos, Paweł Stankiewicz, Wendy K Chung, Eric D Austin

Faculty, Staff and Students Publications

Over the past decade, recognition of the profound impact of the TBX4 (T-box 4) gene, which encodes a member of the evolutionarily conserved family of T-box–containing transcription factors, on respiratory diseases has emerged. The developmental importance of TBX4 is emphasized by the association of TBX4 variants with congenital disorders involving respiratory and skeletal structures; however, the exact role of TBX4 in human development remains incompletely understood. Here, we discuss the developmental, tissue-specific, and pathological TBX4 functions identified through human and animal studies and review the published TBX4 variants resulting in variable disease phenotypes. We also outline future research …

Rational Design Of A Self-Assembling High Performance Organic Nanofluorophore For Intraoperative Nir-Ii Image-Guided Tumor Resection Of Oral Cancer, Xianwei Sun, Praveen Kumar Chintakunta, Andrew A Badachhape, Rohan Bhavane, Huan-Jui Lee, David S Yang, Zbigniew Starosolski, Ketan B Ghaghada, Peter G Vekilov, Ananth V Annapragada, Eric A Tanifum

Faculty, Staff and Students Publications

The first line of treatment for most solid tumors is surgical resection of the primary tumor with adequate negative margins. Incomplete tumor resections with positive margins account for over 75% of local recurrences and the development of distant metastases. In cases of oral cavity squamous cell carcinoma (OSCC), the rate of successful tumor removal with adequate margins is just 50–75%. Advanced real‐time imaging methods that improve the detection of tumor margins can help improve success rates,overall safety, and reduce the cost. Fluorescence imaging in the second near‐infrared (NIR‐II) window has the potential to revolutionize the field due to its high …

Total Daily Energy Expenditure Has Declined Over The Past Three Decades Due To Declining Basal Expenditure, Not Reduced Activity Expenditure, John R Speakman, Jasper M A De Jong, Srishti Sinha, Klaas R Westerterp, Yosuke Yamada, Hiroyuki Sagayama, Philip N Ainslie, Liam J Anderson, Lenore Arab, Kweku Bedu-Addo, Stephane Blanc, Alberto G Bonomi, Pascal Bovet, Soren Brage, Maciej S Buchowski, Nancy F Butte, Stefan G J A Camps, Jamie A Cooper, Richard Cooper, Sai Krupa Das, Peter S W Davies, Lara R Dugas, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W Fudge, Melanie Gillingham, Santu Ghosh, Annelies H Goris, Michael Gurven, Lewis G Halsey, Catherine Hambly, Hinke H Haisma, Daniel Hoffman, Sumei Hu, Annemiek M Joosen, Jennifer L Kaplan, Peter Katzmarzyk, William E Kraus, Robert F Kushner, William R Leonard, Marie Löf, Corby K Martin, Eric Matsiko, Anine C Medin, Erwin P Meijer, Marian L Neuhouser, Theresa A Nicklas, Robert M Ojiambo, Kirsi H Pietiläinen, Jacob Plange-Rhule, Guy Plasqui, Ross L Prentice, Susan B Racette, David A Raichlen, Eric Ravussin, Leanne M Redman, Susan B Roberts, Michael C Rudolph, Luis B Sardinha, Albertine J Schuit, Analiza M Silva, Eric Stice, Samuel S Urlacher, Giulio Valenti, Ludo M Van Etten, Edgar A Van Mil, Brian M Wood, Jack A Yanovski, Tsukasa Yoshida, Xueying Zhang, Alexia J Murphy-Alford, Cornelia U Loechl, Anura Kurpad, Amy H Luke, Herman Pontzer, Matthew S Rodeheffer, Jennifer Rood, Dale A Schoeller, William W Wong

Faculty, Staff and Student Publications

Obesity is caused by prolonged positive energy balance1,2. Whether reduced energy expenditure stemming from reduced activity levels contributes, is debated3,4. Here we used the IAEA DLW database on energy expenditure of adults in the USA and Europe (n = 4799) to explore patterns in total (TEE: n=4799), basal (BEE: n = 1432) and physical activity energy expenditure (AEE: n = 1432) over time. In both sexes total energy expenditure (TEE) adjusted for body composition and age declined with time, while adjusted AEE increased over time. In males adjusted BEE decreased significantly, but …

Dnmt3a-Coordinated Splicing Governs The Stem State Switch Towards Differentiation In Embryonic And Haematopoietic Stem Cells, Raghav Ramabadran, Jarey H Wang, Jaime M Reyes, Anna G Guzman, Sinjini Gupta, Carina Rosas, Lorenzo Brunetti, Michael C Gundry, Ayala Tovy, Hali Long, Tianpeng Gu, Sean M Cullen, Siddhartha Tyagi, Danielle Rux, Jean J Kim, Steven M Kornblau, Michael Kyba, Fabio Stossi, Rachel E Rau, Koichi Takahashi, Thomas F Westbrook, Margaret A Goodell

Faculty, Staff and Student Publications

Upon stimulation by extrinsic stimuli, stem cells initiate a programme that enables differentiation or self-renewal. Disruption of the stem state exit has catastrophic consequences for embryogenesis and can lead to cancer. While some elements of this stem state switch are known, major regulatory mechanisms remain unclear. Here we show that this switch involves a global increase in splicing efficiency coordinated by DNA methyltransferase 3α (DNMT3A), an enzyme typically involved in DNA methylation. Proper activation of murine and human embryonic and haematopoietic stem cells depends on messenger RNA processing, influenced by DNMT3A in response to stimuli. DNMT3A coordinates splicing through recruitment …

Familial Hypercholesterolemia In The Electronic Medical Records And Genomics Network: Prevalence, Penetrance, Cardiovascular Risk, And Outcomes After Return Of Results, Ozan Dikilitas, Alborz Sherafati, Seyedmohammad Saadatagah, Benjamin A Satterfield, David C Kochan, Katherine C Anderson, Wendy K Chung, Scott J Hebbring, Zachary M Salvati, Richard R Sharp, Amy C Sturm, Richard A Gibbs, Robb Rowley, Eric Venner, Jodell E Linder, Laney K Jones, Emma F Perez, Josh F Peterson, Gail P Jarvik, Heidi L Rehm, Hana Zouk, Dan M Roden, Marc S Williams, Teri A Manolio, Iftikhar J Kullo

Faculty, Staff and Students Publications

BACKGROUND: The implications of secondary findings detected in large-scale sequencing projects remain uncertain. We assessed prevalence and penetrance of pathogenic familial hypercholesterolemia (FH) variants, their association with coronary heart disease (CHD), and 1-year outcomes following return of results in phase III of the electronic medical records and genomics network.

METHODS: Adult participants (n=18 544) at 7 sites were enrolled in a prospective cohort study to assess the clinical impact of returning results from targeted sequencing of 68 actionable genes, including

RESULTS: The prevalence of FH-associated pathogenic variants was 1 in 188 (69 of 13,019 unselected participants). Penetrance was 87.5%. The …

Temporal Single-Cell Atlas Of Non-Neuronal Retinal Cells Reveals Dynamic, Coordinated Multicellular Responses To Central Nervous System Injury, Inbal Benhar, Jiarui Ding, Wenjun Yan, Irene E Whitney, Anne Jacobi, Malika Sud, Grace Burgin, Karthik Shekhar, Nicholas M Tran, Chen Wang, Zhigang He, Joshua R Sanes, Aviv Regev

Faculty, Staff and Students Publications

Non-neuronal cells are key to the complex cellular interplay that follows central nervous system insult. To understand this interplay, we generated a single-cell atlas of immune, glial and retinal pigment epithelial cells from adult mouse retina before and at multiple time points after axonal transection. We identified rare subsets in naive retina, including interferon (IFN)-response glia and border-associated macrophages, and delineated injury-induced changes in cell composition, expression programs and interactions. Computational analysis charted a three-phase multicellular inflammatory cascade after injury. In the early phase, retinal macroglia and microglia were reactivated, providing chemotactic signals concurrent with infiltration of CCR2+ monocytes from …