Biomedical Informatics Commons^™

Evaluation Of Scrub Typhus Surveillance, Alwar District, Rajasthan, India, July-August 2020, Surendra M Prajapati, Kanica Kaushal, Simmi Tiwari, Ajit Shewale, Tushar Nale, Tanzin Dikid

Faculty, Staff and Student Publications

INTRODUCTION: Scrub typhus is one of the most underreported and fatal illnesses accounting for 23% of all febrile illness. Rajasthan reported cases during 2018-2019 in state reporting system but did not report any case to central Integrated Disease Surveillance Programme (IDSP) unit. We evaluated the Scrub typhus surveillance system in Alwar district, Rajasthan, with the objective of describing and evaluating the system and providing evidence-based recommendations to identify gaps.

MATERIAL AND METHODS: In cross-sectional study, we reviewed records and conducted key informant interviews at district- and block-level health facilities. Using US Centers for Disease Control guidelines, we evaluated the system …

How Influential Are Medical School Curriculum And Other Medical School Characteristics In Students' Selecting Pathology As A Specialty?, Cindy B Mccloskey, Mark Brissette, John Michael Childs, Amanda Lofgreen, Kristen Johnson, Melissa R George, Ashley M Holloman, Bronwyn Bryant, Mary P Berg, Lisa Ross Dixon, Julie Katz Karp, Barbara E C Knollmann-Ritschel, Victor Gerardo Prieto, Charles F Timmons, Robert D Hoffman

Faculty, Staff and Student Publications

There has been a significant decline in the number of United States allopathic medical students matching to pathology residency programs. Data acquired from the American Association of Medical Colleges (AAMC) show sustained variation in the medical school production of students who go on to pathology residency. When divided into groups based on the medical school's historical volume of graduates entering pathology, the schools in groups labeled Group 1 and Group 2 produced significantly higher and lower proportions of pathology residents, respectively. This study aimed to identify what medical school curriculum elements and other medical school characteristics might explain the differences …

Tuning The Thermodynamic, Optical, And Rheological Properties Of Thermoresponsive Polymer Solutions Via Silica Nanoparticle Shape And Concentration, Christopher A P Neal, Valeria León, Michelle C Quan, Nondumiso O Chibambo, Michelle A Calabrese

Faculty, Staff and Student Publications

HYPOTHESIS: The shape and quantity of hydrophilic silica nanoparticles (NPs) can be used to tune the microstructure, rheology, and stability of phase-separating polymer solutions. In thermoresponsive polymer systems, silica nanospheres are well-studied whereas anisotropic NPs have little literature precedent. Here, we hypothesize that NP shape and concentration lower the onset of rheological and turbidimetric transitions of aqueous poly(N-isopropyl acrylamide) (PNIPAM) solutions.

EXPERIMENTS: Differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), turbidimetry, and oscillatory rheology are utilized to examine interactions between NPs, PNIPAM, and water and to track changes in phase separation and rheological properties due to NP concentration and shape. …

Next-Generation Ctla-4 Targeting Molecules And Combination Therapy: Promising Strategies For Improving Cancer Immunotherapy, Nils-Petter Rudqvist, Manushak Avagyan, Dhan Chand

Faculty, Staff and Student Publications

Radiation therapy and anti-CTLA-4 combination therapy can induce meaningful responses in some patients. Adding CD40 may provide additional benefit. Next-generation anti-CTLA-4 antibodies, such as botensilimab, are showing promise in clinical trials. Combining botensilimab with RT and/or CD40 agonist may offer additional benefits for challenging tumor types.

Stereotactic Body Proton Therapy For Early Stage Non-Small Cell Lung Cancer – Technical Challenges And Solutions: The Md Anderson Experience, X Ronald Zhu, Yuting Li, Ming Yang, Thomas J Whitaker, Paige A Taylor, Xiaodong Zhang, Falk Poenisch, Narayan Sahoo, Zhongxing Liao, Joe Y Chang

Faculty, Staff and Student Publications

Our randomized clinical study comparing stereotactic body radiotherapy (SBRT) and stereotactic body proton therapy (SBPT) for early stage non-small cell lung cancer (NSCLC) was closed prematurely owing to poor enrollment, largely because of lack of volumetric imaging and difficulty in obtaining insurance coverage for the SBPT group. In this article, we describe technology improvements in our new proton therapy center, particularly in image guidance with cone beam CT (CBCT) and CT on rail (CTOR), as well as motion management with real-time gated proton therapy (RGPT) and optical surface imaging. In addition, we have a treatment planning system that provides better …

A Randomized Double-Blind Prospective Study Comparing The Efficacy Of Subperiosteal And Periarticular Injections Of A Local Anesthetic For Postoperative Pain Management After Total Knee Arthroplasty, Reza Minaei, Mohammad Salehpour, Emad Kouhestani, Mahshid Ghasemi

Faculty, Staff and Student Publications

OBJECTIVES: Total knee arthroplasty (TKA) serves as an effective surgical treatment method for advanced osteoarthritis (OA). Nonetheless, it is associated with postoperative pain that can influence patients' functional outcome. This study aimed to compare the analgesic effect of subperiosteal and periarticular injection methods of a special local anesthetic in patients who underwent TKA.

METHODS: This double-blind prospective clinical study was conducted on patients with advanced knee OA who underwent TKA. Patients were randomly divided into two groups, with a local anesthetic (21 ml) administered either in periarticular (P group) or subperiosteal (S group) forms prior to wound closure. The local …

Multi-Faceted Role Of Lrp1 In The Immune System, Olga Sizova, Lisa St John, Qing Ma, Jeffrey J Molldrem

Faculty, Staff and Student Publications

Graft versus host disease (GVHD) represents the major complication after allogeneic hematopoietic stem cell transplantation (Allo-SCT). GVHD-prone patients rely on GVHD prophylaxis (e.g. methotrexate) and generalized anti-GVHD medical regimen (glucocorticoids). New anti-GVHD therapy strategies are being constantly explored, however there is an urgent need to improve current treatment, since GVHD-related mortality reaches 22% within 5 years in patients with chronic GVHD. This review is an attempt to describe a very well-known receptor in lipoprotein studies - the low-density lipoprotein receptor related protein 1 (LRP1) - in a new light, as a potential therapeutic target for GVHD prevention and treatment. Our …

Colorectal Surveillance Outcomes From An Institutional Longitudinal Cohort Of Lynch Syndrome Carriers, Gabriel Del Carmen, Laura Reyes-Uribe, Daniel Goyco, Kyera Evans, Charles M Bowen, Jennifer L Kinnison, Valerie O Sepeda, Diane M Weber, Julie Moskowitz, Maureen E Mork, Selvi Thirumurthi, Patrick M Lynch, Miguel A Rodriguez-Bigas, Melissa W Taggart, Y Nancy You, Eduardo Vilar

Faculty, Staff and Student Publications

OBJECTIVE: Lynch Syndrome (LS) carriers have a significantly increased risk of developing colorectal cancer (CRC) during their lifetimes. Further stratification of this patient population may help in identifying additional risk factors that predispose to colorectal carcinogenesis. In most LS patients CRC may arise from adenomas, although an alternative non-polypoid carcinogenesis pathway has been proposed for

DESIGN: We collected demographics, genetic, colonoscopy, and pathology results from a total of 163 LS carriers who obtained regular screening care at MD Anderson Cancer Center. Data were extracted from the electronic health records into a REDCap database for analysis. Logistic regressions were performed to …

Exercise And Ischemia-Activated Pathways In Limb Muscle Angiogenesis And Vascular Regeneration, Vihang A Narkar

Faculty, Staff and Student Publications

Exercise has a profound effect on cardiovascular disease, particularly through vascular remodeling and regeneration. Peripheral artery disease (PAD) is one such cardiovascular condition that benefits from regular exercise or rehabilitative physical therapy in terms of slowing the progression of disease and delaying amputations. Various rodent pre-clinical studies using models of PAD and exercise have shed light on molecular pathways of vascular regeneration. Here, I review key exercise-activated signaling pathways (nuclear receptors, kinases, and hypoxia inducible factors) in the skeletal muscle that drive paracrine regenerative angiogenesis. The rationale for highlighting the skeletal muscle is that it is the largest organ recruited …

Fanconi Anemia Caused By Biallelic Inactivation Of Brca2 Can Present With An Atypical Cancer Phenotype In Adulthood, Kara N Maxwell, Vishal Patel, Kevin T Nead, Shana Merrill, Dana Clark, Qinqin Jiang, Bradley Wubbenhorst, Kurt D'Andrea, Roger B Cohen, Susan M Domchek, Jennifer J D Morrissette, Roger A Greenberg, Daria V Babushok, Katherine L Nathanson

Faculty, Staff and Student Publications

Inherited biallelic pathogenic variants (PVs) in BRCA2 cause Fanconi Anemia complementation group D1 (FA-D1), a severe pediatric bone marrow failure and high-risk cancer syndrome. We identified biallelic BRCA2 PVs in a young adult with multiple basal cell carcinomas, adult-onset colorectal cancer and small cell neuroendocrine carcinoma, without bone marrow failure. No PVs were identified in any other known cancer susceptibility gene, and there was no evidence of reversion mosaicism. The proband's deceased sister had a classic FA-D1 presentation and was shown to carry the same biallelic BRCA2 PVs. A lymphoblastoid cell line derived from the proband demonstrated hypersensitivity to DNA …

Circulating Tumor Dna Sequencing Of Pediatric Solid And Brain Tumor Patients: An Institutional Feasibility Study, Ross Mangum, Jacquelyn Reuther, Koel Sen Baksi, Ilavarasi Gandhi, Ryan C Zabriskie, Alva Recinos, Robin Raesz-Martinez, Frank Y Lin, Samara L Potter, Andrew C Sher, Stephen F Kralik, Carrie A Mohila, Murali M Chintagumpala, Donna Muzny, Jianhong Hu, Richard A Gibbs, Kevin E Fisher, Juan Carlos Bernini, Jonathan Gill, Timothy C Griffin, Gail E Tomlinson, Kelly L Vallance, Sharon E Plon, Angshumoy Roy, D Williams Parsons

Faculty, Staff and Students Publications

The potential of circulating tumor DNA (ctDNA) analysis to serve as a real-time "liquid biopsy" for children with central nervous system (CNS) and non-CNS solid tumors remains to be fully elucidated. We conducted a study to investigate the feasibility and potential clinical utility of ctDNA sequencing in pediatric patients enrolled on an institutional clinical genomics trial. A total of 240 patients had tumor DNA profiling performed during the study period. Plasma samples were collected at study enrollment from 217 patients and then longitudinally from a subset of patients. Successful cell-free DNA extraction and quantification occurred in 216 of 217 (99.5%) …

Ageing And Rejuvenation Of Tissue Stem Cells And Their Niches, Anne Brunet, Margaret A Goodell, Thomas A Rando

Faculty, Staff and Students Publications

Most adult organs contain regenerative stem cells, often organized in specific niches. Stem cell function is critical for tissue homeostasis and repair upon injury, and it is dependent on interactions with the niche. During ageing, stem cells decline in their regenerative potential and ability to give rise to differentiated cells in the tissue, which is associated with a deterioration of tissue integrity and health. Ageing-associated changes in regenerative tissue regions include defects in maintenance of stem cell quiescence, differentiation ability and bias, clonal expansion and infiltration of immune cells in the niche. In this Review, we discuss cellular and molecular …

Cloud-Native Distributed Genomic Pileup Operations, Marek Wiewiórka, Agnieszka Szmurło, Paweł Stankiewicz, Tomasz Gambin

Faculty, Staff and Students Publications

MOTIVATION: Pileup analysis is a building block of many bioinformatics pipelines, including variant calling and genotyping. This step tends to become a bottleneck of the entire assay since the straightforward pileup implementations involve processing of all base calls from all alignments sequentially. On the other hand, a distributed version of the algorithm faces the intrinsic challenge of splitting reads-oriented file formats into self-contained partitions to avoid costly data exchange between computational nodes.

RESULTS: Here, we present a scalable, distributed and efficient implementation of a pileup algorithm that is suitable for deploying in cloud computing environments. In particular, we implemented: (i) …

Advanced Photon Counting Ct Imaging Pipeline For Cardiac Phenotyping Of Apolipoprotein E Mouse Models, Alex J Allphin, Ali Mahzarnia, Darin P Clark, Yi Qi, Zay Y Han, Prajwal Bhandari, Ketan B Ghaghada, Alexandra Badea, Cristian T Badea

Faculty, Staff and Students Publications

Background: Cardiovascular disease (CVD) is associated with the apolipoprotein E (APOE) gene and lipid metabolism. This study aimed to develop an imaging-based pipeline to comprehensively assess cardiac structure and function in mouse models expressing different APOE genotypes using photon-counting computed tomography (PCCT).

Methods: 123 mice grouped based on APOE genotype (APOE2, APOE3, APOE4, APOE knockout (KO)), gender, human NOS2 factor, and diet (control or high fat) were used in this study. The pipeline included PCCT imaging on a custom-built system with contrast-enhanced in vivo imaging and intrinsic cardiac gating, spectral and temporal iterative reconstruction, spectral decomposition, and deep learning cardiac …

Symptoms, Physical Activity, And Biomarkers In Children At The End Of Leukemia Maintenance Therapy, Mary C Hooke, Derek L Salisbury, Michelle A Mathiason, Alicia S Kunin-Batson, Audrey Blommer, Jessica Hutter, Pauline Mitby, Ida Moore, Susan Whitman, Olga Taylor, Michael E Scheurer, Marilyn J Hockenberry

Faculty, Staff and Students Publications

Background: Symptoms in children with acute lymphocytic leukemia (ALL) change over the trajectory of treatment but little is known about their symptoms as treatment ends. Physical activity may help decrease symptom distress and is vital for ongoing development. The role of biomarkers in symptom science is emerging. The purpose of the study was to explore relationships between self-report of symptoms and physical activity, actigraphy measures, and cerebrospinal fluid (CSF) biomarkers.

Methods: Participants were children who were ages 3 to 18 years at the time of ALL diagnosis and were now in the last 12-week cycle of ALL maintenance. Self-reports of …

Checkpoint Blockade In Unresectable Pleural Mesothelioma: Event Horizon For Multimodal Therapy, R Taylor Ripley, Aaron S Mansfield, Boris Sepesi, Raphael Bueno, Bryan M Burt

Faculty, Staff and Students Publications

No abstract provided.

A Student-Designed Multimodal Sex- And Gender-Based Women's Health Elective Program: Advocacy Curriculum For Medical Students, Lauren M Conroy, Danna Ghafir, Maitreyi Narayan, Hunter Mcspedden, Samuel Neher, S Shahrukh Hashmi, Rebecca Lunstroth

Faculty, Staff and Student Publications

OBJECTIVES: The objective of this article is to describe the design and implementation of a multimodal, student-driven, sex- and gender-based women's health (SGBWH) elective with a curricular focus on patient and legislative advocacy. In this single arm, pre/post design, interventional study, we detail and evaluate the use of social media, newsletters, and round-table discussions in conjunction with a traditional lecture-based educational format to engage medical students in a virtual learning environment.

METHODS: We developed a 22-week SGBWH curriculum for pre-clinical and clinical medical students, which included a series of lectures on multi-specialty and gender-inclusive topics related to SGBWH, small group …

Large-Scale Exome Array Summary Statistics Resources For Glycemic Traits To Aid Effector Gene Prioritization, Sara M Willems, Natasha H J Ng, Juan Fernandez, Rebecca S Fine, Eleanor Wheeler, Jennifer Wessel, Hidetoshi Kitajima, Gaelle Marenne, Xueling Sim, Hanieh Yaghootkar, Shuai Wang, Sai Chen, Yuning Chen, Yii-Der Ida Chen, Niels Grarup, Ruifang Li-Gao, Tibor V Varga, Jennifer L Asimit, Shuang Feng, Rona J Strawbridge, Erica L Kleinbrink, Tarunveer S Ahluwalia, Ping An, Emil V Appel, Dan E Arking, Juha Auvinen, Lawrence F Bielak, Nathan A Bihlmeyer, Jette Bork-Jensen, Jennifer A Brody, Archie Campbell, Audrey Y Chu, Gail Davies, Ayse Demirkan, James S Floyd, Franco Giulianini, Xiuqing Guo, Stefan Gustafsson, Anne U Jackson, Johanna Jakobsdottir, Marjo-Riitta Järvelin, Richard A Jensen, Stavroula Kanoni, Sirkka Keinanen-Kiukaanniemi, Man Li, Yingchang Lu, Jian'an Luan, Alisa K Manning, Jonathan Marten, Karina Meidtner, Dennis O Mook-Kanamori, Taulant Muka, Giorgio Pistis, Bram Prins, Kenneth M Rice, Serena Sanna, Albert Vernon Smith, Jennifer A Smith, Lorraine Southam, Heather M Stringham, Vinicius Tragante, Sander W Van Der Laan, Helen R Warren, Jie Yao, Andrianos M Yiorkas, Weihua Zhang, Wei Zhao, Mariaelisa Graff, Heather M Highland, Anne E Justice, Eirini Marouli, Carolina Medina-Gomez, Saima Afaq, Wesam A Alhejily, Najaf Amin, Folkert W Asselbergs, Lori L Bonnycastle, Michiel L Bots, Ivan Brandslund, Ji Chen, John Danesh, Renée De Mutsert, Abbas Dehghan, Tapani Ebeling, Paul Elliott, Epic-Interact Consortium, Aliki-Eleni Farmaki, Jessica D Faul, Paul W Franks, Steve Franks, Andreas Fritsche, Anette P Gjesing, Mark O Goodarzi, Vilmundur Gudnason, Göran Hallmans, Tamara B Harris, Karl-Heinz Herzig, Marie-France Hivert, Torben Jørgensen, Marit E Jørgensen, Pekka Jousilahti, Eero Kajantie, Maria Karaleftheri, Sharon L R Kardia, Leena Kinnunen, Heikki A Koistinen, Pirjo Komulainen, Peter Kovacs, Johanna Kuusisto, Markku Laakso, Leslie A Lange, Lenore J Launer, Aaron Leong, Jaana Lindström, Jocelyn E Manning Fox, Satu Männistö, Nisa M Maruthur, Leena Moilanen, Antonella Mulas, Mike A Nalls, Matthew Neville, James S Pankow, Alison Pattie, Eva R B Petersen, Hannu Puolijoki, Asif Rasheed, Paul Redmond, Frida Renström, Michael Roden, Danish Saleheen, Juha Saltevo, Kai Savonen, Sylvain Sebert, Tea Skaaby, Kerrin S Small, Alena Stančáková, Jakob Stokholm, Konstantin Strauch, E-Shyong Tai, Kent D Taylor, Betina H Thuesen, Anke Tönjes, Emmanouil Tsafantakis, Tiinamaija Tuomi, Jaakko Tuomilehto, Understanding Society Scientific Group;, Matti Uusitupa, Marja Vääräsmäki, Ilonca Vaartjes, Magdalena Zoledziewska, Goncalo Abecasis, Beverley Balkau, Hans Bisgaard, Alexandra I Blakemore, Matthias Blüher, Heiner Boeing, Eric Boerwinkle, Klaus Bønnelykke, Erwin P Bottinger, Mark J Caulfield, John C Chambers, Daniel I Chasman, Ching-Yu Cheng, Francis S Collins, Josef Coresh, Francesco Cucca, Gert J De Borst, Ian J Deary, George Dedoussis, Panos Deloukas, Hester M Den Ruijter, Josée Dupuis, Michele K Evans, Ele Ferrannini, Oscar H Franco, Harald Grallert, Torben Hansen, Andrew T Hattersley, Caroline Hayward, Joel N Hirschhorn, Arfan Ikram, Erik Ingelsson, Fredrik Karpe, Kay-Tee Kaw, Wieland Kiess, Jaspal S Kooner, Antje Körner, Timo Lakka, Claudia Langenberg, Lars Lind, Cecilia M Lindgren, Allan Linneberg, Leonard Lipovich, Ching-Ti Liu, Jun Liu, Yongmei Liu, Ruth J F Loos, Patrick E Macdonald, Karen L Mohlke, Andrew D Morris, Patricia B Munroe, Alison Murray, Sandosh Padmanabhan, Colin N A Palmer, Gerard Pasterkamp, Oluf Pedersen, Patricia A Peyser, Ozren Polasek, David Porteous, Michael A Province, Bruce M Psaty, Rainer Rauramaa, Paul M Ridker, Olov Rolandsson, Patrik Rorsman, Frits R Rosendaal, Igor Rudan, Veikko Salomaa, Matthias B Schulze, Robert Sladek, Blair H Smith, Timothy D Spector, John M Starr, Michael Stumvoll, Cornelia M Van Duijn, Mark Walker, Nick J Wareham, David R Weir, James G Wilson, Tien Yin Wong, Eleftheria Zeggini, Alan B Zonderman, Jerome I Rotter, Andrew P Morris, Michael Boehnke, Jose C Florez, Mark I Mccarthy, James B Meigs, Anubha Mahajan, Robert A Scott, Anna L Gloyn, Inês Barroso

Faculty, Staff and Student Publications

Background: Genome-wide association studies for glycemic traits have identified hundreds of loci associated with these biomarkers of glucose homeostasis. Despite this success, the challenge remains to link variant associations to genes, and underlying biological pathways.

Methods: To identify coding variant associations which may pinpoint effector genes at both novel and previously established genome-wide association loci, we performed meta-analyses of exome-array studies for four glycemic traits: glycated hemoglobin (HbA1c, up to 144,060 participants), fasting glucose (FG, up to 129,665 participants), fasting insulin (FI, up to 104,140) and 2hr glucose post-oral glucose challenge (2hGlu, up to 57,878). In addition, we performed network …

Methodological Considerations In Pisces 3: A Randomized, Placebo-Controlled Study Of Intracerebral Stem Cells In Subjects With Disability Following An Ischemic Stroke, Daniel T Laskowitz, Keith W Muir, Sean I Savitz, Lawrence R Wechsler, Julie G Pilitsis, Scott Y Rahimi, Richard L Beckman, Vincent Holmes, Peng R Chen, Laura Juel, Deborah Koltai, Brad J Kolls

Faculty, Staff and Student Publications

Background and hypothesis: At present, there are no medical interventions proven to improve functional recovery in patients with subacute stroke. We hypothesize that the intraparenchymal administration of CTX0E03, a conditionally immortalized neural stem cell line, linked with a standardized rehabilitation therapy regimen for the upper limb, would improve functional outcomes in patients 6-12 months after an index ischemic stroke.

Study design: PISCES III was designed as a multicenter prospective, sham-controlled, outcome-blinded randomized clinical trial. Eligibility required a qualifying ischemic stroke 6-12 months prior to surgical intervention. Patients must be between 35 and 75 years of age and have residual moderate …

Msdrp: A Deep Learning Model Based On Multisource Data For Predicting Drug Response, Haochen Zhao, Xiaoyu Zhang, Qichang Zhao, Yaohang Li, Jianxin Wang

Computer Science Faculty Publications

Motivation: Cancer heterogeneity drastically affects cancer therapeutic outcomes. Predicting drug response in vitro is expected to help formulate personalized therapy regimens. In recent years, several computational models based on machine learning and deep learning have been proposed to predict drug response in vitro. However, most of these methods capture drug features based on a single drug description (e.g. drug structure), without considering the relationships between drugs and biological entities (e.g. target, diseases, and side effects). Moreover, most of these methods collect features separately for drugs and cell lines but fail to consider the pairwise interactions between drugs and cell …

Novornabreak: Local Assembly For Novel Splice Junction And Fusion Transcript Detection From Rna-Seq Data, Yukun Tan, Vakul Mohanty, Shaoheng Liang, Jinzhuang Dou, Jun Ma, Kun Hee Kim, Marc Jan Bonder, Xinghua Shi, Charles Lee, Zechen Chong, Ken Chen

Faculty, Staff and Student Publications

We present novoRNABreak, a unified framework for cancer specific novel splice junction and fusion transcript detection in RNA-seq data obtained from human cancer samples. novoRNABreak is based on a local assembly model, which offers a tradeoff between the alignment-based and de novo whole transcriptome assembly (WTA) methods. This approach is accurate and sensitive in assembling novel junctions that are difficult to directly align or have multiple alignments. Additionally, it is more efficient due to the strategy that focuses on junctions rather than full length transcripts. The performance of novoRNABreak is demonstrated by a comprehensive set of experiments using synthetic data …

Automated Brain Metastases Segmentation With A Deep Dive Into False-Positive Detection, Hamidreza Ziyaee, Carlos E Cardenas, D Nana Yeboa, Jing Li, Sherise D Ferguson, Jason Johnson, Zijian Zhou, Jeremiah Sanders, Raymond Mumme, Laurence Court, Tina Briere, Jinzhong Yang

Faculty, Staff and Student Publications

Purpose: The clinical management of brain metastases after stereotactic radiosurgery (SRS) is difficult, because a physician must review follow-up magnetic resonance imaging (MRI) scans to determine treatment outcome, which is often labor intensive. The purpose of this study was to develop an automated framework to contour brain metastases in MRI to help treatment planning for SRS and understand its limitations.

Methods and materials: Two self-adaptive nnU-Net models trained on postcontrast 3-dimensional T1-weighted MRI scans from patients who underwent SRS were analyzed. Performance was evaluated by computing positive predictive value (PPV), sensitivity, and Dice similarity coefficient (DSC). The training and testing …

Pathologic And Molecular Insights In Nodal T-Follicular Helper Cell Lymphomas, Mario L Marques-Piubelli, Catalina Amador, Francisco Vega

Faculty, Staff and Student Publications

T-follicular helper (TFH) cells are one of the T-cell subsets with a critical role in the regulation of germinal center (GC) reactions. TFH cells contribute to the positive selection of GC B-cells and promote plasma cell differentiation and antibody production. TFH cells express a unique phenotype characterized by PD-1hi, ICOShi, CD40Lhi, CD95hi, CTLAhi, CCR7lo, and CXCR5hi . Three main subtypes of nodal TFH lymphomas have been described: 1) angioimmunoblastic-type, 2) follicular-type, and 3) not otherwise specified (NOS). The diagnosis of these neoplasms can be challenging, and it is rendered based on a combination of clinical, laboratory, histopathologic, immunophenotypic, and molecular …

When Guilt Works: A Comprehensive Meta-Analysis Of Guilt Appeals, Wei Peng, Qian Huang, Bingjing Mao, Di Lun, Ekaterina Malova, Jazmyne V Simmons, Nick Carcioppolo

Faculty, Staff and Student Publications

Introduction: Guilt appeals are widely used as a persuasive approach in various areas of practice. However, the strength and direction of the persuasive effects of guilt appeals are mixed, which could be influenced by theoretical and methodological factors.

Method: The present study is a comprehensive meta-analysis of 26 studies using a random-effects model to assess the persuasive effects of guilt appeals. In total, 127 effect sizes from seven types of persuasive outcomes (i.e., guilt, attitude, behavior, behavioral intention, non-guilt emotions, motivation, and cognition) were calculated based on 7,512 participants.

Results: The analysis showed a small effect size of guilt appeals …

Sociodemographic Differences In Menthol Cigarette Use In The United States, Rajesh Talluri, Sanjay Shete

Faculty, Staff and Student Publications

Background: Menthol cigarette use is associated with higher smoking initiation and reduced smoking cessation. We investigated sociodemographic differences in menthol and nonmenthol cigarette use in the United States.

Methods: We used the most recent available data from the May 2019 wave of the nationally-representative Tobacco Use Supplement to the Current Population Survey. The survey weights were used to estimate the national prevalence of individuals who currently smoke among individuals who use menthol and nonmenthol cigarettes. Survey-weighted logistic regression methods were used to estimate the association of menthol cigarette use with formerly smoking cigarettes and attempting to quit within the past …

Applying Ht-Saxs To Chemical Ligand Screening, Chris A Brosey, Runze Shen, Davide Moiani, Darin E Jones, Kathryn Burnett, Greg L Hura, John A Tainer

Faculty, Staff and Student Publications

Chemical probes are invaluable tools for investigating essential biological processes. Understanding how small-molecule probes engage biomolecular conformations is critical to developing their functional selectivity. High-throughput solution X-ray scattering is well-positioned to profile target-ligand complexes during probe development, bringing conformational insight and selection to traditional ligand binding assays. Access to high-quality synchrotron SAXS datasets and high-throughput data analysis now allows routine academic users to incorporate conformational information into small-molecule development pipelines. Here we describe a general approach for benchmarking and preparing HT-SAXS chemical screens from small fragment libraries. Using the allosteric oxidoreductase Apoptosis-Inducing Factor (AIF) as an exemplary system, we illustrate …

Adverse Events Of Immune Checkpoint Therapy Alone Versus When Combined With Vascular Endothelial Growth Factor Inhibitors: A Pooled Meta-Analysis Of 1735 Patients, Iuliia Kovalenko, Wern Lynn Ng, Yimin Geng, Yinghong Wang, Pavlos Msaouel, Shailender Bhatia, Petros Grivas, Raed Benkhadra, Omar Alhalabi

Faculty, Staff and Student Publications

Background: Combining immune checkpoint therapy (ICT) and vascular endothelial growth factor inhibitors (VEGFi) may result in increased treatment-related and immune-related adverse events (TRAEs and irAEs) compared to ICT alone. This metanalysis was conducted to identify prospective phase II or III clinical studies that evaluated the toxicity profile of ICT + VEGFi compared to ICT alone.

Methods: A systematic search was performed across all cancer types and major databases until August 10, 2022, and screening was done by two independent investigators. Inclusion criteria included phase 2 or 3 studies with at least one arm of patients treated with combination therapy and …

Cd73-Generated Extracellular Adenosine Promotes Resolution Of Neutrophil-Mediated Tissue Injury And Restrains Metaplasia In Pancreatitis, Baylee J O'Brien, Erika Y Faraoni, Lincoln N Strickland, Zhibo Ma, Victoria Mota, Samantha Mota, Xuebo Chen, Tingting Mills, Holger K Eltzschig, Kathleen E Delgiorno, Jennifer M Bailey-Lundberg

Faculty, Staff and Student Publications

Pancreatitis is currently the leading cause of gastrointestinal hospitalizations in the US. This condition occurs in response to abdominal injury, gallstones, chronic alcohol consumption or, less frequently, the cause remains idiopathic. CD73 is a cell surface ecto‐5′‐nucleotidase that generates extracellular adenosine, which can contribute to resolution of inflammation by binding adenosine receptors on infiltrating immune cells. We hypothesized genetic deletion of CD73 would result in more severe pancreatitis due to decreased generation of extracellular adenosine. CD73 knockout (CD73 −/−) and C57BL/6 (wild type, WT) mice were used to evaluate the progression and response of caerulein‐induced acute and chronic pancreatitis. …

Positron Emission Tomography Derived Metrics In Relapsed Or Refractory Large B-Cell Lymphoma With Residual Disease Before Autologous Stem Cell Transplant, Hua-Jay J Cherng, Guofan Xu, Lei Feng, Raphael Steiner, Luis Fayad, Paolo Strati, Ranjit Nair, Loretta J Nastoupil, Hun Ju Lee, Sattva S Neelapu, Christopher R Flowers, Maria Rodriguez, Michael Wang, Fredrick Hagemeister, Chelsea C Pinnix, Jeremy Ramdial, Samer Srour, Yago Nieto, Katayoun Rezvani, Richard Champlin, Partow Kebriaei, Jason Westin, Homer A Macapinlac, Elizabeth Shpall, Sairah Ahmed

Faculty, Staff and Student Publications

Salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) is a potentially curative treatment for patients with relapsed or refractory large B-cell lymphoma (rrLBCL) with chemosensitive disease. A18 F-fluorodeoxyglucose positron emission tomography (PET) scan after salvage chemotherapy is used to assess response and eligibility for ASCT, but metrics for chemosensitivity in patients with residual disease are not well defined. We performed a single-centre retrospective analysis of 92 patients with a partial response or stable disease after salvage chemotherapy for rrLBCL who received ASCT to investigate PET-derived parameters and their prognostic utility. The Deauville 5-point Scale (D-5PS) score, …

The Kynurenine Pathway Presents Multi-Faceted Metabolic Vulnerabilities In Cancer, Ricardo A León-Letelier, Rongzhang Dou, Jody Vykoukal, Ali Hussein Abdel Sater, Edwin Ostrin, Samir Hanash, Johannes F Fahrmann

Faculty, Staff and Student Publications

The kynurenine pathway (KP) and associated catabolites play key roles in promoting tumor progression and modulating the host anti-tumor immune response. To date, considerable focus has been on the role of indoleamine 2,3-dioxygenase 1 (IDO1) and its catabolite, kynurenine (Kyn). However, increasing evidence has demonstrated that downstream KP enzymes and their associated metabolite products can also elicit tumor-microenvironment immune suppression. These advancements in our understanding of the tumor promotive role of the KP have led to the conception of novel therapeutic strategies to target the KP pathway for anti-cancer effects and reversal of immune escape. This review aims to 1) …