Digital Commons Network^™

Ensuring Trust In Genomics Research, Erman Ayday, Jaideep Vaidya, Xiaoqian Jiang, Amalio Telenti

Faculty, Staff and Student Publications

Reproducibility, transparency, representation, and privacy underpin the trust on genomics research in general and genome-wide association studies (GWAS) in particular. Concerns about these issues can be mitigated by technologies that address privacy protection, quality control, and verifiability of GWAS. However, many of the existing technological solutions have been developed in isolation and may address one aspect of reproducibility, transparency, representation, and privacy of GWAS while unknowingly impacting other aspects. As a consequence, the current patchwork of technological tools only partially and in an overlapping manner address issues with GWAS, sometimes even creating more problems. This paper addresses the progress in …

Exercise Training Reduces The Inflammatory Response And Promotes Intestinal Mucosa-Associated Immunity In Lynch Syndrome, Nan Deng, Laura Reyes-Uribe, Johannes F Fahrmann, Whittney S Thoman, Mark F Munsell, Jennifer B Dennison, Eunice Murage, Ranran Wu, Ernest T Hawk, Selvi Thirumurthi, Patrick M Lynch, Christina M Dieli-Conwright, Alexander J Lazar, Sonali Jindal, Khoi Chu, Manoj Chelvanambi, Karen Basen-Engquist, Yisheng Li, Jennifer A Wargo, Florencia Mcallister, James P Allison, Padmanee Sharma, Krishna M Sinha, Samir Hanash, Susan C Gilchrist, Eduardo Vilar

Faculty, Staff and Student Publications

PURPOSE: Lynch syndrome (LS) is a hereditary condition with a high lifetime risk of colorectal and endometrial cancers. Exercise is a non-pharmacologic intervention to reduce cancer risk, though its impact on patients with LS has not been prospectively studied. Here, we evaluated the impact of a 12-month aerobic exercise cycling intervention in the biology of the immune system in LS carriers.

PATIENTS AND METHODS: To address this, we enrolled 21 patients with LS onto a non-randomized, sequential intervention assignation, clinical trial to assess the effect of a 12-month exercise program that included cycling classes 3 times weekly for 45 minutes …

Nanobomb Optical Coherence Elastography In Multilayered Phantoms, Maryam Hatami, Dmitry Nevozhay, Manmohan Singh, Alexander Schill, Paul Boerner, Salavat Aglyamov, Konstantin Sokolov, Kirill V Larin

Faculty, Staff and Student Publications

Many tissues are composed of layered structures, and a better understanding of the changes in the layered tissue biomechanics can enable advanced guidance and monitoring of therapy. The advent of elastography using longitudinally propagating shear waves (LSWs) has created the prospect of a high-resolution assessment of depth-dependent tissue elasticity. Laser activation of liquid-to-gas phase transition of dye-loaded perfluorocarbon (PFC) nanodroplets (a.k.a., nanobombs) can produce highly localized LSWs. This study aims to leverage the potential of photoactivation of nanobombs to incudce LSWs with very high-frequency content in wave-based optical coherence elastography (OCE) to estimate the elasticity gradient with high resolution. In …

A Framework For Standardised Tissue Sampling And Processing During Resection Of Diffuse Intracranial Glioma: Joint Recommendations From Four Rano Groups, Philipp Karschnia, Marion Smits, Guido Reifenberger, Emilie Le Rhun, Benjamin M Ellingson, Norbert Galldiks, Michelle M Kim, Jason T Huse, Oliver Schnell, Patrick N Harter, Malte Mohme, Expert Rater Panel, Louisa Von Baumgarten, Nathalie L Albert, Raymond Y Huang, Minesh P Mehta, Martin Van Den Bent, Michael Weller, Michael A Vogelbaum, Susan M Chang, Mitchel S Berger, Joerg-Christian Tonn

Faculty, Staff and Student Publications

Surgical resection represents the standard of care for people with newly diagnosed diffuse gliomas, and the neuropathological and molecular profile of the resected tissue guides clinical management and forms the basis for research. The Response Assessment in Neuro-Oncology (RANO) consortium is an international, multidisciplinary effort that aims to standardise research practice in neuro-oncology. These recommendations represent a multidisciplinary consensus from the four RANO groups: RANO resect, RANO recurrent glioblastoma, RANO radiotherapy, and RANO/PET for a standardised workflow to achieve a representative tumour evaluation in a disease characterised by intratumoural heterogeneity, including recommendations on which tumour regions should be surgically sampled, …

Α-Synuclein Is The Major Platelet Isoform But Is Dispensable For Activation, Secretion, And Thrombosis, Alexis N. Smith, Smita Joshi, Harry Chanzu, Hammodah Rawhi Hammodah Alfar, Kanakanagavalli Shravani Prakhya, Sidney W. Whiteheart

Saha Cardiovascular Research Center Faculty Publications

Platelets play many roles in the vasculature ensuring proper hemostasis and maintaining integrity. These roles are facilitated, in part, by cargo molecules released from platelet granules via Soluble NSF Attachment Protein Receptor (SNARE) mediated membrane fusion, which is controlled by several protein-protein interactions. Chaperones have been characterized for t-SNAREs (i.e. Munc18b for Syntaxin-11), but none have been clearly identified for v-SNAREs. α- Synuclein has been proposed as a v-SNARE chaperone which may affect SNARE-complex assembly, fusion pore opening, and thus secretion. Despite its abundance and that it is the only isoform present, α-synuclein’s role in platelet secretion is uncharacterized. In …

Dean's Research Newsletter, November 2023, Neil W. Schluger

SOM Dean's Research Newsletter

No abstract provided.

Dha Shortage Causes The Early Degeneration Of Photoreceptors And Rpe In Mice With Peroxisomal Β-Oxidation Deficiency, Daniëlle Swinkels, Sai Kocherlakota, Yannick Das, Adriaan D. Dane, Eric J.M. Wever, Frédéric M. Vaz, Nicolas G. Bazan, Paul P. Van Veldhoven, Myriam Baes

School of Medicine Faculty Publications

PURPOSE. Patients deficient in peroxisomal β-oxidation, which is essential for the synthesis of docosahexaenoic acid (DHA, C22:6n-3) and breakdown of very-long-chain polyunsaturated fatty acids (VLC-PUFAs), both important components of photoreceptor outer segments, develop retinopathy present with retinopathy. The representative mouse model lacking the central enzyme of this pathway, multifunctional protein 2 (Mfp2−/−), also show early-onset retinal decay and cell-autonomous retinal pigment epithelium (RPE) degeneration, accompanied by reduced plasma and retinal DHA levels. In this study, we investigated whether DHA supplementation can rescue the retinal degeneration of Mfp2−/− mice. METHODS. Mfp2+/− breeding pairs and their offspring were fed a 0.12% DHA …

Multi-Omics Analysis Of Circulating Exosomes In Adherent Long-Term Treated Osa Patients, Abdelnaby Khalyfa, Jose M. Marin, David Sanz-Rubio, Zhen Lyu, Trupti Joshi, David Gozal

Biomedical Sciences

Obstructive sleep apnea (OSA) is a highly prevalent chronic disease affecting nearly a billion people globally and increasing the risk of multi-organ morbidity and overall mortality. However, the mechanisms underlying such adverse outcomes remain incompletely delineated. Extracellular vesicles (exosomes) are secreted by most cells, are involved in both proximal and long-distance intercellular communication, and contribute toward homeostasis under physiological conditions. A multi-omics integrative assessment of plasma-derived exosomes from adult OSA patients prior to and after 1-year adherent CPAP treatment is lacking. We conducted multi-omic integrative assessments of plasma-derived exosomes from adult OSA patients prior to and following 1-year adherent CPAP …

A Human Mitofusin 2 Mutation Can Cause Mitophagic Cardiomyopathy, Antonietta Franco, Jiajia Li, Daniel P Kelly, Ray E Hershberger, Ali J Marian, Renate M Lewis, Moshi Song, Xiawei Dang, Alina D Schmidt, Mary E Mathyer, John R Edwards, Cristina De Guzman Strong, Gerald W Dorn

Faculty, Staff and Student Publications

Cardiac muscle has the highest mitochondrial density of any human tissue, but mitochondrial dysfunction is not a recognized cause of isolated cardiomyopathy. Here, we determined that the rare mitofusin (MFN) 2 R400Q mutation is 15-20× over-represented in clinical cardiomyopathy, whereas this specific mutation is not reported as a cause of MFN2 mutant-induced peripheral neuropathy, Charcot-Marie-Tooth disease type 2A (CMT2A). Accordingly, we interrogated the enzymatic, biophysical, and functional characteristics of MFN2 Q400 versus wild-type and CMT2A-causing MFN2 mutants. All MFN2 mutants had impaired mitochondrial fusion, the canonical MFN2 function. Compared to MFN2 T105M that lacked catalytic GTPase activity and exhibited normal …

The Development, Content And Response Process Validation Of A Caregiver-Reported Severity Measure For Cdkl5 Deficiency Disorder, Sonja I Ziniel, Alexandra Mackie, Jacinta Saldaris, Helen Leonard, Peter Jacoby, Eric D Marsh, Bernhard Suter, Elia Pestana-Knight, Heather E Olson, Dana Price, Judith Weisenberg, Rajsekar Rajaraman, Gina Vanderveen, Tim A Benke, Jenny Downs, Scott Demarest

Faculty, Staff and Students Publications

BACKGROUND: CDKL5 Deficiency Disorder (CDD) is a severe X-linked developmental and epileptic encephalopathy. Existing developmental outcome measures have floor effects and cannot capture incremental changes in symptoms. We modified the caregiver portion of a CDD clinical severity assessment (CCSA) and assessed content and response-process validity.

METHODS: We conducted cognitive interviews with 15 parent caregivers of 1-39-year-old children with CDD. Caregivers discussed their understanding and concerns regarding appropriateness of both questions and answer options. Item wording and questionnaire structure were adjusted iteratively to ensure questions were understood as intended.

RESULTS: The CCSA was refined during three rounds of cognitive interviews into …

Aso Silencing Of A Glycosyltransferase, Poglut1, Improves The Liver Phenotypes In Mouse Models Of Alagille Syndrome, Nima Niknejad, Duncan Fox, Jennifer L Burwinkel, Neda Zarrin-Khameh, Soomin Cho, Armand Soriano, Ashley E Cast, Mario F Lopez, Kari A Huppert, Frank Rigo, Stacey S Huppert, Paymaan Jafar-Nejad, Hamed Jafar-Nejad

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Paucity of intrahepatic bile ducts (BDs) is caused by various etiologies and often leads to cholestatic liver disease. For example, in patients with Alagille syndrome (ALGS), which is a genetic disease primarily caused by mutations in jagged 1 ( JAG1) , BD paucity often results in severe cholestasis and liver damage. However, no mechanism-based therapy exists to restore the biliary system in ALGS or other diseases associated with BD paucity. Based on previous genetic observations, we investigated whether postnatal knockdown of the glycosyltransferase gene protein O -glucosyltransferase 1 ( Poglut1) can improve the ALGS liver phenotypes in …

Baseline Leptin Predicts Response To Metformin In Adolescents With Type 1 Diabetes And Increased Body Mass Index, Heba M Ismail, Souptik Barua, Johnny Wang, Ashutosh Sabharwal, Ingrid Libman, Fida Bacha, Kristen J Nadeau, Mustafa Tosur, Maria J Redondo

Faculty, Staff and Students Publications

No abstract provided.

Examining Potential Modifiers Of Human Skin And Plasma Carotenoid Responses In A Randomized Trial Of A Carotenoid-Containing Juice Intervention, Stephanie B Jilcott Pitts, Qiang Wu, Nancy E Moran, Melissa N Laska, Lisa Harnack

Children’s Nutrition Research Center Staff Publications

Background: Skin carotenoid measurements are emerging as a valid and reliable indicator of fruit and vegetable intake and carotenoid intake. However, little is known about the extent to which skin carotenoid responsivity to dietary changes differs based on demographic and physiologic characteristics.

Objectives: This study examined potential effect modifiers of skin carotenoid and plasma carotenoid responses to a carotenoid-rich juice intervention.

Methods: We leveraged data from 2 arms of a 3-site randomized controlled trial of a carotenoid-containing juice intervention (moderate dose = 6 ounces juice, 4 mg total carotenoids/d, high dose = 12 ounces juice, 8 mg total carotenoids/d) (n …

Clinical Outcome And Therapeutic Impact On Neuroendocrine Neoplasms Of The Breast: A National Cancer Database Study, Libo Yang, Heather Lin, Yu Shen, Madhuchhanda Roy, Constance Albarracin, Qingqing Ding, Lei Huo, Hui Chen, Bing Wei, Hong Bu, Isabelle Bedrosian, Yun Wu

Faculty, Staff and Student Publications

Purpose: Neuroendocrine neoplasms (NENs) of the breast are rare and not well-studied. NEN are subcategorized as well-differentiated neuroendocrine tumor (NET) and poorly differentiated neuroendocrine carcinoma (NEC). The objectives of the current study were to review the clinicopathologic features of NENs, therapeutic efficacy of current systemic therapy and clinical outcomes of NEN of the breast.

Methods: Between 2004 and 2015, 420 NET, 205 NEC, 146 Adenocarcinoma with NE differentiation (ACNED) and 1,479,520 of invasive carcinoma, not otherwise specified (IC-NOS) of the breast were identified in the National Caner Database. Overall survival was compared among groups using Kaplan-Meier method and Log-rank test. …

Remotely Delivered Cancer Genetic Testing In The Making Genetic Testing Accessible (Magenta) Trial: A Randomized Clinical Trial, Elizabeth M Swisher, Nadine Rayes, Deborah Bowen, Christine B Peterson, Barbara M Norquist, Tara Coffin, Kathleen Gavin, Deborah Polinsky, Jamie Crase, Jamie N Bakkum-Gamez, Stephanie V Blank, Mark F Munsell, Denise Nebgen, Gini F Fleming, Olufunmilayo I Olopade, Sherman Law, Alicia Zhou, Douglas A Levine, Alan D'Andrea, Karen H Lu

Faculty, Staff and Student Publications

Importance: Requiring personalized genetic counseling may introduce barriers to cancer risk assessment, but it is unknown whether omitting counseling could increase distress.

Objective: To assess whether omitting pretest and/or posttest genetic counseling would increase distress during remote testing.

Design, setting, and participants: Making Genetic Testing Accessible (MAGENTA) was a 4-arm, randomized noninferiority trial testing the effects of individualized pretest and/or posttest genetic counseling on participant distress 3 and 12 months posttest. Participants were recruited via social and traditional media, and enrollment occurred between April 27, 2017, and September 29, 2020. Participants were women aged 30 years or older, English-speaking, US …

Next-Generation Chimeric Antigen Receptors For T- And Natural Killer-Cell Therapies Against Cancer, Ye Li, Katayoun Rezvani, Hind Rafei

Faculty, Staff and Student Publications

Adoptive cellular therapy using chimeric antigen receptor (CAR) T cells has led to a paradigm shift in the treatment of various hematologic malignancies. However, the broad application of this approach for myeloid malignancies and solid cancers has been limited by the paucity and heterogeneity of target antigen expression, and lack of bona fide tumor-specific antigens that can be targeted without cross-reactivity against normal tissues. This may lead to unwanted on-target off-tumor toxicities that could undermine the desired antitumor effect. Recent advances in synthetic biology and genetic engineering have enabled reprogramming of immune effector cells to enhance their selectivity toward tumors, …

Stepwise Requirements For Polymerases Δ And Θ In Theta-Mediated End Joining, Susanna Stroik, Juan Carvajal-Garcia, Dipika Gupta, Alyssa Edwards, Adam Luthman, David W Wyatt, Rachel L Dannenberg, Wanjuan Feng, Thomas A Kunkel, Gaorav P Gupta, Mark Hedglin, Richard Wood, Sylvie Doublié, Eli Rothenberg, Dale A Ramsden

Faculty, Staff and Student Publications

Timely repair of chromosomal double-strand breaks is required for genome integrity and cellular viability. The polymerase theta-mediated end joining pathway has an important role in resolving these breaks and is essential in cancers defective in other DNA repair pathways, thus making it an emerging therapeutic target1 It requires annealing of 2-6 nucleotides of complementary sequence, microhomologies, that are adjacent to the broken ends, followed by initiation of end-bridging DNA synthesis by polymerase θ. However, the other pathway steps remain inadequately defined, and the enzymes required for them are unknown. Here we demonstrate requirements for exonucleolytic digestion of unpaired 3' tails …

Methods For Objective Assessment Of Skin Involvement In Systemic Sclerosis, Ruhani Desai, Harshdeep Chawla, Kirill Larin, Shervin Assassi

Faculty, Staff and Student Publications

Purpose of review: Skin fibrosis is the most prominent disease manifestation of systemic sclerosis (SSc). Although the treatment for other SSc manifestations has expanded over the years, there is limited progress in identifying effective treatment options for SSc skin involvement. This is in part due to limitations in the utilized outcome measures for assessment of skin fibrosis. This review focuses on different emerging assessment tools for SSc skin involvement and their potential use for clinical care and multicenter trials.

Recent findings: Durometer and other device-based methodologies requiring application of direct pressure to the affected skin have been studied in SSc. …

Iron Overload Induces Cerebral Endothelial Senescence In Aged Mice And In Primary Culture In A Sex-Dependent Manner, Brian Noh, Maria Pilar Blasco-Conesa, Syed Mushfiqur Rahman, Sheelu Monga, Rodney Ritzel, Gary Guzman, Yun-Ju Lai, Bhanu Priya Ganesh, Akihiko Urayama, Louise D Mccullough, Jose Felix Moruno-Manchon

Faculty, Staff and Student Publications

Iron imbalance in the brain negatively affects brain function. With aging, iron levels increase in the brain and contribute to brain damage and neurological disorders. Changes in the cerebral vasculature with aging may enhance iron entry into the brain parenchyma, leading to iron overload and its deleterious consequences. Endothelial senescence has emerged as an important contributor to age-related changes in the cerebral vasculature. Evidence indicates that iron overload may induce senescence in cultured cell lines. Importantly, cells derived from female human and mice generally show enhanced senescence-associated phenotype, compared with males. Thus, we hypothesize that cerebral endothelial cells (CEC) derived …

Clinical And Molecular Features Of Long-Term Response To Immune Checkpoint Inhibitors In Patients With Advanced Non-Small Cell Lung Cancer, Rohit Thummalapalli, Biagio Ricciuti, Chaitanya Bandlamudi, Daniel Muldoon, Hira Rizvi, Arielle Elkrief, Jia Luo, Joao V Alessi, Federica Pecci, Giuseppe Lamberti, Alessandro Di Federico, Lingzhi Hong, Jianjun Zhang, John V Heymach, Don L Gibbons, Andrew J Plodkowski, Vignesh Ravichandran, Mark T A Donoghue, Chad Vanderbilt, Marc Ladanyi, Charles M Rudin, Mark G Kris, Gregory J Riely, Jamie E Chaft, Matthew D Hellmann, Natalie I Vokes, Mark M Awad, Adam J Schoenfeld

Faculty, Staff and Student Publications

PURPOSE: We sought to identify features of patients with advanced non-small cell lung cancer (NSCLC) who achieve long-term response (LTR) to immune checkpoint inhibitors (ICI), and how these might differ from features predictive of short-term response (STR).

EXPERIMENTAL DESIGN: We performed a multicenter retrospective analysis of patients with advanced NSCLC treated with ICIs between 2011 and 2022. LTR and STR were defined as response ≥ 24 months and response < 12 months, respectively. Tumor programmed death ligand 1 (PD-L1) expression, tumor mutational burden (TMB), next-generation sequencing (NGS), and whole-exome sequencing (WES) data were analyzed to identify characteristics enriched in patients achieving LTR compared with STR and non-LTR.

RESULTS: Among 3,118 patients, 8% achieved LTR and 7% achieved STR, with 5-year overall survival (OS) of 81% and 18% among LTR and STR patients, respectively. High TMB (≥50th percentile) enriched …

Performance Of Ct-Based Deep Learning In Diagnostic Assessment Of Suspicious Lateral Lymph Nodes In Papillary Thyroid Cancer: A Prospective Diagnostic Study, Guibin Zheng, Haicheng Zhang, Fusheng Lin, Mark Zafereo, Neil Gross, Peng Sun, Yang Liu, Haiqing Sun, Guochang Wu, Shujian Wei, Jia Wu, Ning Mao, Guojun Li, Guoyang Wu, Haitao Zheng, Xicheng Song

Faculty, Staff and Student Publications

Background: Preoperative evaluation of the metastasis status of lateral lymph nodes (LNs) in papillary thyroid cancer is challenging. Strategies for using deep learning to diagnosis of lateral LN metastasis require additional development and testing. This study aimed to build a deep learning-based model to distinguish benign lateral LNs from metastatic lateral LNs in papillary thyroid cancer and test the model's diagnostic performance in a real-world clinical setting.

Methods: This was a prospective diagnostic study. An ensemble model integrating a three-dimensional residual network algorithm with clinical risk factors available before surgery was developed based on computed tomography images of lateral LNs …

Mitochondrial Health Index Correlates With Plasma Circulating Cell-Free Mitochondrial Dna In Bipolar Disorder, Rafaela C Cordeiro, Camila N C Lima, Gabriel R Fries, Giovana Zunta-Soares, Jair C Soares, João Quevedo, Giselli Scaini

Faculty, Staff and Student Publications

Although mitochondrial dysfunction is known to play an essential role in the pathophysiology of bipolar disorder (BD), there is a glaring gap in our understanding of how mitochondrial dysfunction can modulate clinical phenotypes. An emerging paradigm suggests mitochondria play an important non-energetic role in adaptation to stress, impacting cellular resilience and acting as a source of systemic allostatic load. Known as mitochondrial allostatic load, this (phenomenon) occurs when mitochondria are unable to recalibrate and maintain cell homeostasis. This study aimed to evaluate the composite mitochondrial health index (MHI) in BD subjects and non-psychiatry controls. We will also explore whether lower …

Comparison Between Viral Vector And Mrna Based Covid-19 Vaccination In Prevalence And Severity Of Regional Immune Reactions, And 18f-Fdg Pet/Ct Features, Narjess Ayati, Scott Evans, S Rasoul Zakavi, Simon M Gruenewald

Faculty, Staff and Student Publications

Objective(s):

The coronavirus pandemic caused by SARS-CoV-2 commenced in late 2019, and global wide vaccination appears to be the only reasonable solution to fight this dreadful virus. There are two main types of COVID-19 immunization using viral vector and mRNA-based vaccines. However, the impact of each of type on 18F-FDG PET/CT needs to be accurately assessed. This study aimed to compare the 18F-FDG PET/CT features of these two types of COVID-19 vaccines.

Methods:

A total of 188 patients referred for 18F-FDG PET/CT with a recent history of either BioNTech/Pfizer or AstraZeneca COVID-19 vaccination, and a control group of 40 patients …

Immune Cell Identity Behind The Ktrans Mapping Of Mouse Glioblastoma, Yanrong Zhang, Olivier Keunen, Anna Golebiewska, Marco Gerosa, Jing Wang, Sara Natasha Ghobadi, Ai Huang, Qingyi Hou, Frezghi G Habte, Ningrui Li, Gerry Grant, Ramasamy Paulmurugan, Kevin S Lee, Max Wintermark

Faculty, Staff and Student Publications

Dynamic contrast-enhanced MR imaging (DCE-MRI) can assess the integrity of the blood brain barrier (BBB) and has been used in GBM patients to determine glioma grade, predict prognosis, evaluate treatment response, and differentiate treatment-induced effect from recurrence. The volume transfer constant Ktrans is the most frequently used metric in tumor assessment. Based on previous studies that a higher WHO grade of brain tumor was associated with greater impairments of immunity and and that Ktrans value was associated with the pathological grading, the relationship between differential composition of immune cells in GBM tissue and dynamic changes in Ktrans mapping was anticipated …

Real-Time Liver Motion Estimation Via Deep Learning-Based Angle-Agnostic X-Ray Imaging, Hua-Chieh Shao, Yunxiang Li, Jing Wang, Steve Jiang, You Zhang

Faculty, Staff and Student Publications

Background: Real-time liver imaging is challenged by the short imaging time (within hundreds of milliseconds) to meet the temporal constraint posted by rapid patient breathing, resulting in extreme under-sampling for desired 3D imaging. Deep learning (DL)-based real-time imaging/motion estimation techniques are emerging as promising solutions, which can use a single X-ray projection to estimate 3D moving liver volumes by solved deformable motion. However, such techniques were mostly developed for a specific, fixed X-ray projection angle, thereby impractical to verify and guide arc-based radiotherapy with continuous gantry rotation.

Purpose: To enable deformable motion estimation and 3D liver imaging from individual X-ray …

Blood-Based Migration Signature Biomarker Panel Discriminates Early Stage New Onset Diabetes Related Pancreatic Ductal Adenocarcinoma From Type 2 Diabetes, Seetharaman Balasenthil, Suyu Liu, Jianliang Dai, William R Bamlet, Gloria Petersen, Suresh T Chari, Anirban Maitra, Nanyue Chen, Subrata Sen, Ann Mcneill Killary

Faculty, Staff and Student Publications

Background and aims: While type 2 diabetes is a well-known risk factor for pancreatic ductal adenocarcinoma (PDAC), PDAC-induced new-onset diabetes (PDAC-NOD) is a manifestation of underlying PDAC. In this study, we sought to identify potential blood-based biomarkers for distinguishing PDAC-NOD from type 2 diabetes (T2DM) without PDAC.

Materials and methods: By ELISA analysis, a migration signature biomarker panel comprising tissue factor pathway inhibitor (TFPI), tenascin C (TNC-FNIII-C) and CA 19-9 was analyzed in plasma samples from 50 PDAC-NOD and 50 T2DM controls.

Results: Both TFPI (area under the curve (AUC) 0.71) and TNC-FNIII-C (AUC 0.69) outperformed CA 19-9 (AUC 0.60) …

Circulating Micrornas And Cytokines As Prognostic Biomarkers For Doxorubicin-Induced Cardiac Injury And For Evaluating The Effectiveness Of An Exercise Intervention, Prince Jeyabal, Anchit Bhagat, Fei Wang, Michael Roth, J Andrew Livingston, Susan C Gilchrist, Jose Banchs, Michelle A T Hildebrandt, Joya Chandra, Anita Deswal, Efstratios Koutroumpakis, Jian Wang, Najat C Daw, Theresa A Honey, Eugenie S Kleinerman

Faculty, Staff and Student Publications

Purpose: To define a set of biomarkers that can be used to identify patients at high risk of developing late doxorubicin (DOX)-induced cardiac morbidity with the goal of focused monitoring and early interventions.

Experimental design: Mice received phosphate buffered saline or DOX 2.5 mg/kg 2x/week for 2 weeks. Blood samples were obtained before and after therapy for quantification of miRNAs (6 and 24 hours), cytokines (24 hours), and troponin (24 hours, 4 and 6 weeks). Cardiac function was evaluated using echocardiography before and 24 hours after therapy. To assess the effectiveness of exercise intervention in preventing DOX-induced cardiotoxicity blood samples …

Cell-Autonomous Effects Of Apoe4 In Restricting Microglial Response In Brain Homeostasis And Alzheimer’S Disease, Chia-Chen Liu, Na Wang, Yuanxin Chen, Yasuteru Inoue, Francis Shue, Yingxue Ren, Minghui Wang, Wenhui Qiao, Tadafumi C Ikezu, Zonghua Li, Jing Zhao, Yuka Martens, Sydney V Doss, Cassandra L Rosenberg, Suren Jeevaratnam, Lin Jia, Ana-Caroline Raulin, Fangfang Qi, Yiyang Zhu, Alla Alnobani, Joshua Knight, Yixing Chen, Cynthia Linares, Aishe Kurti, John D Fryer, Bin Zhang, Long-Jun Wu, Betty Y S Kim, Guojun Bu

Faculty, Staff and Student Publications

Microglial involvement in Alzheimer's disease (AD) pathology has emerged as a risk-determining pathogenic event. While apolipoprotein E (APOE) is known to modify AD risk, it remains unclear how microglial apoE impacts brain cognition and AD pathology. Here, using conditional mouse models expressing apoE isoforms in microglia and central nervous system-associated macrophages (CAMs), we demonstrate a cell-autonomous effect of apoE3-mediated microglial activation and function, which are negated by apoE4. Expression of apoE3 in microglia/CAMs improves cognitive function, increases microglia surrounding amyloid plaque and reduces amyloid pathology and associated toxicity, whereas apoE4 expression either compromises or has no effects on these outcomes …

Identification Of Novel Genetic Loci For Risk Of Multiple Myeloma By Functional Annotation, Angelica Macauda, Klara Briem, Alyssa Clay-Gilmour, Wendy Cozen, Asta Försti, Matteo Giaccherini, Chiara Corradi, Juan Sainz, Yasmeen Niazi, Rob Ter Horst, Yang Li, Mihai G Netea, Ulla Vogel, Kari Hemminki, Susan L Slager, Judit Varkonyi, Vibeke Andersen, Elzbieta Iskierka-Jazdzewska, Joaquin Mártinez-Lopez, Jan Zaucha, Nicola J Camp, S Vincent Rajkumar, Agnieszka Druzd-Sitek, Parveen Bhatti, Stephen J Chanock, Shaji K Kumar, Edyta Subocz, Grzegorz Mazur, Stefano Landi, Mitchell J Machiela, Andrés Jerez, Aaron D Norman, Michelle A T Hildebrandt, Katalin Kadar, Sonja I Berndt, Elad Ziv, Gabriele Buda, Arnon Nagler, Charles Dumontet, Malgorzata Raźny, Marzena Watek, Aleksandra Butrym, Norbert Grzasko, Marek Dudzinski, Malwina Rybicka-Ramos, Eva-Laure Matera, Ramón García-Sanz, Hartmut Goldschmidt, Krzysztof Jamroziak, Artur Jurczyszyn, Esther Clavero, Graham G Giles, Matteo Pelosini, Daria Zawirska, Marcin Kruszewski, Herlander Marques, Eva Haastrup, José Manuel Sánchez-Maldonado, Uta Bertsch, Marcin Rymko, Marc-Steffen Raab, Elizabeth E Brown, Jonathan N Hofmann, Celine Vachon, Daniele Campa, Federico Canzian

Faculty, Staff and Student Publications

No abstract provided.

Cost-Effectiveness Of [99mtc]Tilmanocept Relative To [99mtc]Sulfur Colloid For Sentinel Lymph Node Biopsy In Early Stage Oral Cavity Cancer, Karen Y Choi, Qiang Hao, Kathryn Carlisle, Christopher S Hollenbeak, Stephen Y Lai

Faculty, Staff and Student Publications

BACKGROUND: Several studies have demonstrated varying rates of efficacy, reliability, and sensitivity of sentinel lymph node biopsy (SLNB) in identifying occult nodal disease for early stage oral cavity squamous cell carcinoma (OCSCC) depending on the radionuclide agent utilized. No head-to-head comparison of cost or clinical outcomes of SLNB when utilizing [99mTc]tilmanocept versus [99mTc]sulfur colloid has been performed. The goal of this study was to develop a decision model to compare the cost-effectiveness of [99mTc]tilmanocept versus [99mTc]sulfur colloid in early stage OCSCC.

PATIENTS AND METHODS: A decision model of disease and treatment as a function of SLNB was created. Patients with …