Digital Commons Network^™

Measurable Residual Disease Response And Prognosis In Treatment-Naïve Acute Myeloid Leukemia With Venetoclax And Azacitidine, Keith W Pratz, Brian A Jonas, Vinod Pullarkat, Christian Recher, Andre C Schuh, Michael J Thirman, Jacqueline S Garcia, Courtney D Dinardo, Vladimir Vorobyev, Nicola S Fracchiolla, Su-Peng Yeh, Jun Ho Jang, Muhit Ozcan, Kazuhito Yamamoto, Arpad Illes, Ying Zhou, Monique Dail, Brenda Chyla, Jalaja Potluri, Hartmut Döhner

Faculty, Staff and Student Publications

PURPOSE: There is limited evidence on the clinical utility of monitoring measurable residual disease (MRD) in patients with acute myeloid leukemia treated with lower-intensity therapy. Herein, we explored the outcomes of patients treated with venetoclax and azacitidine who achieved composite complete remission (CRc; complete remission + complete remission with incomplete hematologic recovery) and MRD < 10

METHODS: The patients included in this report were treated with venetoclax and azacitidine. Bone marrow aspirate samples for multiparametric flow cytometry assessments were collected for central analysis at baseline, end of cycle 1, and every three cycles thereafter. MRD-negative response was defined as < 1 residual blast per 1,000 leukocytes (< 10

RESULTS: One hundred …

Blood-Based Biomarker Panel For Personalized Lung Cancer Risk Assessment, Johannes F Fahrmann, Tracey Marsh, Ehsan Irajizad, Nikul Patel, Eunice Murage, Jody Vykoukal, Jennifer B Dennison, Kim-Anh Do, Edwin Ostrin, Margaret R Spitz, Stephen Lam, Sanjay Shete, Rafael Meza, Martin C Tammemägi, Ziding Feng, Samir M Hanash

Faculty, Staff and Student Publications

Purpose: To investigate whether a panel of circulating protein biomarkers would improve risk assessment for lung cancer screening in combination with a risk model on the basis of participant characteristics.

Methods: A blinded validation study was performed using prostate lung colorectal ovarian (PLCO) Cancer Screening Trial data and biospecimens to evaluate the performance of a four-marker protein panel (4MP) consisting of the precursor form of surfactant protein B, cancer antigen 125, carcinoembryonic antigen, and cytokeratin-19 fragment in combination with a lung cancer risk prediction model (PLCOm2012) compared with current US Preventive Services Task Force (USPSTF) screening criteria. The 4MP was …

Prognostic Impact Of High Baseline Stromal Tumor-Infiltrating Lymphocytes In The Absence Of Pathologic Complete Response In Early-Stage Triple-Negative Breast Cancer, Nour Abuhadra, Ryan Sun, Jennifer K Litton, Gaiane M Rauch, Clinton Yam, Jeffrey T Chang, Sahil Seth, Roland Bassett, Bora Lim, Alastair M Thompson, Elizabeth Mittendorf, Beatriz E Adrada, Senthil Damodaran, Jason White, Elizabeth Ravenberg, Rosalind Candelaria, Banu Arun, Naoto T Ueno, Lumarie Santiago, Sadia Saleem, Sausan Abouharb, Rashmi K Murthy, Nuhad Ibrahim, Aysegul A Sahin, Vicente Valero, William Fraser Symmans, Debu Tripathy, Stacy Moulder, Lei Huo

Faculty, Staff and Student Publications

High stromal tumor-infiltrating lymphocytes (sTILs) are associated with an improved pathologic complete response (pCR) and survival in triple-negative breast cancer (TNBC). We hypothesized that high baseline sTILs would have a favorable prognostic impact in TNBC patients without a pCR after neoadjuvant chemotherapy (NACT). In this prospective NACT study, pretreatment biopsies from 318 patients with early-stage TNBC were evaluated for sTILs. Recursive partitioning analysis (RPA) was applied to search for the sTIL cutoff best associated with a pCR. With ≥20% sTILs identified as the optimal cutoff, 33% patients had high sTILs (pCR rate 64%) and 67% had low sTILs (pCR rate …

The Impact Of Radiation Dose To Heart Substructures On Major Coronary Events And Patient Survival After Chemoradiation Therapy For Esophageal Cancer, Xin Wang, Nicolas L Palaskas, Brian P Hobbs, Jun-Ichi Abe, Kevin T Nead, Syed Wamique Yusuf, Joerg Hermann, Anita Deswal, Steven H Lin

Faculty, Staff and Student Publications

Simple Summary

Whether it is necessary to evaluate the radiation exposure of cardiac substructures when making radiotherapy plans is one of the current research hotspots. In this cohort study of 355 patients with esophageal cancer, the radiation dose to key coronary substructures such as the left anterior descending artery V30_Gy and mean left main coronary artery was closely associated with major coronary events and overall patient survival, and showed better predictive value than the mean heart dose or heart V30_Gy recommended by current guidelines. Our findings suggest that, in addition to the whole heart, key coronary substructures should …

Identification Of A Novel Microdeletion Causative Of Nance-Horan Syndrome, Mariana Lopez Martinolich, Hope Northrup, Pedro Mancias, Paul Hillman, Kavya Rao, Kate Mowrey

Faculty, Staff and Student Publications

BACKGROUND: Nance-Horan syndrome (NHS) is a rare X-linked genetic disorder characterized by ophthalmologic and dental anomalies as well as dysmorphic facies. The clinical phenotype in males includes congenital cataracts, vision loss, microcornea, nystagmus, microphthalmia, glaucoma, screwdriver blade-shaped incisors, supernumerary maxillary incisors, diastema, delays, intellectual disability, and dysmorphic facies. With the evolution of array-CGH technology, a total of five kindreds with NHS have been reported in the medical literature with microdeletions encompassing the NHS gene rather than sequencing variants.

METHODS: The patient is a 19-year-old male born to non-consanguineous parents with a past medical history of bilateral congenital cataracts, nystagmus, poor …

Clinical Outcomes And Bacterial Characteristics Of Carbapenem-Resistant Klebsiella Pneumoniae Complex Among Patients From Different Global Regions (Crackle-2): A Prospective, Multicentre, Cohort Study, Minggui Wang, Michelle Earley, Liang Chen, Blake M Hanson, Yunsong Yu, Zhengyin Liu, Soraya Salcedo, Eric Cober, Lanjuan Li, Souha S Kanj, Hainv Gao, Jose M Munita, Karen Ordoñez, Greg Weston, Michael J Satlin, Sandra L Valderrama-Beltrán, Kalisvar Marimuthu, Martin E Stryjewski, Lauren Komarow, Courtney Luterbach, Steve H Marshall, Susan D Rudin, Claudia Manca, David L Paterson, Jinnethe Reyes, Maria V Villegas, Scott Evans, Carol Hill, Rebekka Arias, Keri Baum, Bettina C Fries, Yohei Doi, Robin Patel, Barry N Kreiswirth, Robert A Bonomo, Henry F Chambers, Vance G Fowler, Cesar A Arias, David Van Duin, Multi-Drug Resistant Organism Network Investigators

Faculty, Staff and Student Publications

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a global threat. We therefore analysed the bacterial characteristics of CRKP infections and the clinical outcomes of patients with CRKP infections across different countries.

METHODS: In this prospective, multicentre, cohort study (CRACKLE-2), hospitalised patients with cultures positive for CRKP were recruited from 71 hospitals in Argentina, Australia, Chile, China, Colombia, Lebanon, Singapore, and the USA. The first culture positive for CRKP was included for each unique patient. Clinical data on post-hospitalisation death and readmission were collected from health records, and whole genome sequencing was done on all isolates. The primary outcome was a desirability …

Fungi: Friend Or Foe? A Mycobiome Evaluation In Children With Autism And Gastrointestinal Symptoms, Jane Alookaran, Yuying Liu, Thomas A Auchtung, Amirali Tahanan, Manouchehr Hessabi, Parisa Asgarisabet, Mohammad H Rahbar, Nicole Y Fatheree, Deborah A Pearson, Rosleen Mansour, Melissa R Van Arsdall, Fernando Navarro, J Marc Rhoads

Faculty, Staff and Student Publications

Gastrointestinal (GI) symptoms often affect children with autism spectrum disorders (ASD) and GI symptoms have been associated with an abnormal fecal microbiome. There is limited evidence of Candida species being more prevalent in children with ASD. We enrolled 20 children with ASD and GI symptoms (ASD + GI), 10 children with ASD but no GI symptoms (ASD - GI), and 20 from typically developing (TD) children in this pilot study. Fecal mycobiome taxa were analyzed by Internal Transcribed Spacer sequencing. GI symptoms (GI Severity Index [GSI]), behavioral symptoms (Social Responsiveness Scale -2 [SRS-2]), inflammation and fungal immunity (fecal calprotectin and …

Community-Clinic Linkages For Promoting Hiv Prevention: Organizational Networks For Prep Client Referrals And Collaborations, Rebecca L Mauldin, Tamara Al Rawwad, Muhammad Amith, Lisa M Kuhns, John A Schneider, Kayo Fujimoto

Faculty, Staff and Student Publications

Community-clinic linkages may help communities increase HIV pre-exposure prophylaxis (PrEP) uptake. Referrals from community-based organizations may be particularly important for linking Black men who have sex with men (MSM) to PrEP. This study describes PrEP referral and HIV/STI prevention networks among organizations that serve MSM in Houston, TX (N = 40), and Chicago, IL (N = 28), and compares network positions of organizations based on percentage of Black/African American clients. A majority of organizations conducted PrEP awareness/promotion activities, but fewer made PrEP referrals, with little overlap between the collaboration and referral networks. The networks tended to have a …

Type 2 Diabetes Partitioned Polygenic Scores Associate With Disease Outcomes In 454,193 Individuals Across 13 Cohorts, Daniel Dicorpo, Jessica Leclair, Joanne B Cole, Chloé Sarnowski, Fariba Ahmadizar, Lawrence F Bielak, Anneke Blokstra, Erwin P Bottinger, Layal Chaker, Yii-Der I Chen, Ye Chen, Paul S De Vries, Tariq Faquih, Mohsen Ghanbari, Valborg Gudmundsdottir, Xiuqing Guo, Natalie R Hasbani, Dorina Ibi, M Arfan Ikram, Maryam Kavousi, Hampton L Leonard, Aaron Leong, Josep M Mercader, Alanna C Morrison, Girish N Nadkarni, Mike A Nalls, Raymond Noordam, Michael Preuss, Jennifer A Smith, Stella Trompet, Petra Vissink, Jie Yao, Wei Zhao, Eric Boerwinkle, Mark O Goodarzi, Vilmundur Gudnason, J Wouter Jukema, Sharon L R Kardia, Ruth J F Loos, Ching-Ti Liu, Alisa K Manning, Dennis Mook-Kanamori, James S Pankow, H Susan J Picavet, Naveed Sattar, Eleanor M Simonsick, W M Monique Verschuren, Ko Willems Van Dijk, Jose C Florez, Jerome I Rotter, James B Meigs, Josée Dupuis, Miriam S Udler

Faculty, Staff and Student Publications

OBJECTIVE: Type 2 diabetes (T2D) has heterogeneous patient clinical characteristics and outcomes. In previous work, we investigated the genetic basis of this heterogeneity by clustering 94 T2D genetic loci using their associations with 47 diabetes-related traits and identified five clusters, termed β-cell, proinsulin, obesity, lipodystrophy, and liver/lipid. The relationship between these clusters and individual-level metabolic disease outcomes has not been assessed.

RESEARCH DESIGN AND METHODS: Here we constructed individual-level partitioned polygenic scores (pPS) for these five clusters in 12 studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank (n = 454,193) …

Post-Acquisition Hyperpolarized 29silicon Magnetic Resonance Image Processing For Visualization Of Colorectal Lesions Using A User-Friendly Graphical Interface, Caitlin V Mccowan, Duncan Salmon, Jingzhe Hu, Shivanand Pudakalakatti, Nicholas Whiting, Jennifer S Davis, Daniel D Carson, Niki M Zacharias, Pratip K Bhattacharya, Mary C Farach-Carson

Faculty, Staff and Student Publications

Medical imaging devices often use automated processing that creates and displays a self-normalized image. When improperly executed, normalization can misrepresent information or result in an inaccurate analysis. In the case of diagnostic imaging, a false positive in the absence of disease, or a negative finding when disease is present, can produce a detrimental experience for the patient and diminish their health prospects and prognosis. In many clinical settings, a medical technical specialist is trained to operate an imaging device without sufficient background information or understanding of the fundamental theory and processes involved in image creation and signal processing. Here, we …

Brain Stereotactic Radiosurgery Using Mr-Guided Online Adaptive Planning For Daily Setup Variation: An End-To-End Test, Eun Young Han, He Wang, Tina Marie Briere, Debra Nana Yeboa, Themistoklis Boursianis, Georgios Kalaitzakis, Evangelos Pappas, Pamela Castillo, Jinzhong Yang

Faculty, Staff and Student Publications

Online magnetic resonance (MR)-guided radiotherapy is expected to benefit brain stereotactic radiosurgery (SRS) due to superior soft tissue contrast and capability of daily adaptive planning. The purpose of this study was to investigate daily adaptive plan quality with setup variations and to perform an end-to-end test for brain SRS with multiple metastases treated with a 1.5-Tesla MR-Linac (MRL). The RTsafe PseudoPatient Prime brain phantom was used with a delineation insert that includes two predefined structures mimicking gadolinium contrast-enhanced brain lesions. Daily adaptive plans were generated using six preset and six random setup variations. Two adaptive plans per daily MR image …

Long-Term Survival Following Definitive Radiation Therapy For Recurrence Or Oligometastases In Gynecological Malignancies: A Landmark Analysis, Kelsey L Corrigan, Alison Yoder, Brian De, Lilie Lin, Anuja Jhingran, Melissa M Joyner, Patricia J Eifel, Lauren E Colbert, Karen H Lu, Ann H Klopp

Faculty, Staff and Student Publications

Objective: Radiation therapy (RT) may improve outcomes for patients with oligometastatic cancer. We sought to determine if there are long-term survivors treated with definitive RT for recurrent or oligometastatic gynecological cancer (ROMGC), and to evaluate the clinical and disease characteristics of these patients.

Methods: We performed a landmark analysis in 48 patients with ROMGC who survived for ≥5 years following definitive RT of their metastasis. Patient characteristics were extracted from the medical record. DFS was modeled using the Kaplan-Meier method.

Results: This cohort included 20 patients (42%) with ovarian cancer, 16 (33%) with endometrial cancer, 11 (23%) with cervical cancer, …

Monitoring Malignant T-Cell Clones By Direct Tcr Expression Assay In Patients With Leukemic Cutaneous T-Cell Lymphoma During Extracorporeal Photopheresis, Xiao Ni, Sourindra Maiti, Alissa Redko, Pedram Bijani, Madeleine Duvic

Faculty, Staff and Student Publications

Background/purpose: Accurate assessment of malignant T-cell clones in patients with leukemic cutaneous T-cell lymphoma (L-CTCL) is crucial for diagnosis, treatment, and monitoring disease. Although multiple approaches to quantitate malignant T-cell clones have been reported, a cost-effective assay with broad coverage is not available. We report a NanoString-nCounter-Technology-based direct TCR expression assay (DTEA) that was previously developed to quantify both TCR-Vα and TCR-Vβ usages after adoptive immunotherapy. This study was performed to test the effectiveness of DTEA in assessing malignant T-cell clones in L-CTCL patients.

Methods: Total RNAs extracted from peripheral blood mononuclear cells of patients before starting extracorporeal photopheresis (ECP) …

Characterization Of Patient-Derived Bone Marrow Human Mesenchymal Stem Cells As Oncolytic Virus Carriers For The Treatment Of Glioblastoma, Yuzaburo Shimizu, Joy Gumin, Feng Gao, Anwar Hossain, Elizabeth J Shpall, Akihide Kondo, Brittany C Parker Kerrigan, Jing Yang, Daniel Ledbetter, Juan Fueyo, Candelaria Gomez-Manzano, Frederick F Lang

Faculty, Staff and Student Publications

Objective: Delta-24-RGD is an oncolytic adenovirus that is capable of replicating in and killing human glioma cells. Although intratumoral delivery of Delta-24-RGD can be effective, systemic delivery would improve its clinical application. Bone marrow-derived human mesenchymal stem cells (BM-hMSCs) obtained from healthy donors have been investigated as virus carriers. However, it is unclear whether BM-hMSCs can be derived from glioma patients previously treated with marrow-toxic chemotherapy or whether such BM-hMSCs can deliver oncolytic viruses effectively. Herein, the authors undertook a prospective clinical trial to determine the feasibility of obtaining BM-hMSCs from patients with recurrent malignant glioma who were previously exposed …

Of Vascular Defense, Hemostasis, Cancer, And Platelet Biology: An Evolutionary Perspective, David G Menter, Vahid Afshar-Kharghan, John Paul Shen, Stephanie L Martch, Anirban Maitra, Scott Kopetz, Kenneth V Honn, Anil K Sood

Faculty, Staff and Student Publications

We have established considerable expertise in studying the role of platelets in cancer biology. From this expertise, we were keen to recognize the numerous venous-, arterial-, microvascular-, and macrovascular thrombotic events and immunologic disorders are caused by severe, acute-respiratory-syndrome coronavirus 2 (SARS-CoV-2) infections. With this offering, we explore the evolutionary connections that place platelets at the center of hemostasis, immunity, and adaptive phylogeny. Coevolutionary changes have also occurred in vertebrate viruses and their vertebrate hosts that reflect their respective evolutionary interactions. As mammals adapted from aquatic to terrestrial life and the heavy blood loss associated with placentalization-based live birth, platelets …

Methyl-Lysine Readers Phf20 And Phf20l1 Define Two Distinct Gene Expression-Regulating Nsl Complexes, Hieu T Van, Peter R Harkins, Avni Patel, Abhinav K Jain, Yue Lu, Mark T Bedford, Margarida A Santos

Faculty, Staff and Student Publications

The methyl-lysine readers plant homeodomain finger protein 20 (PHF20) and its homolog PHF20-like protein 1 (PHF20L1) are known components of the nonspecific lethal (NSL) complex that regulates gene expression through its histone acetyltransferase activity. In the current model, both PHF homologs coexist in the same NSL complex, although this was not formally tested; nor have the functions of PHF20 and PHF20L1 regarding NSL complex integrity and transcriptional regulation been investigated. Here, we perform an in-depth biochemical and functional characterization of PHF20 and PHF20L1 in the context of the NSL complex. Using mass spectrometry, genome-wide chromatin analysis, and protein-domain mapping, we …

Interleukin-6 Blockade Abrogates Immunotherapy Toxicity And Promotes Tumor Immunity, Ahmed Omar Kaseb, Elshad Hasanov, Hop Sanderson Tran Cao, Lianchun Xiao, Jean-Nicolas Vauthey, Sunyoung S Lee, Betul Gok Yavuz, Yehia I Mohamed, Aliya Qayyum, Sonali Jindal, Fei Duan, Sreyashi Basu, Shalini S Yadav, Courtney Nicholas, Jing Jing Sun, Kanwal Pratap Singh Raghav, Asif Rashid, Kristen Carter, Yun Shin Chun, Ching-Wei David Tzeng, Divya Sakamuri, Li Xu, Ryan Sun, Vittorio Cristini, Laura Beretta, James C Yao, Robert A Wolff, James Patrick Allison, Padmanee Sharma

Faculty, Staff and Student Publications

BACKGROUND: Hepatocellular carcinoma has high recurrence rates after surgery; however, there are no approved standard-of-care neoadjuvant or adjuvant therapies. Immunotherapy has been shown to improve survival in advanced hepatocellular carcinoma; we therefore aimed to evaluate the safety and tolerability of perioperative immunotherapy in resectable hepatocellular carcinoma.

METHODS: In this single-centre, randomised, open-label, phase 2 trial, patients with resectable hepatocellular carcinoma were randomly assigned (1:1) to receive 240 mg of nivolumab intravenously every 2 weeks (for up to three doses before surgery at 6 weeks) followed in the adjuvant phase by 480 mg of nivolumab intravenously every 4 weeks for 2 …

Metabolic Stress Induces Gd2+ Cancer Stem Cell-Like Phenotype In Triple-Negative Breast Cancer, Appalaraju Jaggupilli, Stanley Ly, Khoa Nguyen, Vivek Anand, Bin Yuan, Fouad El-Dana, Yuanqing Yan, Zoe Arvanitis, Danthasinghe Waduge Badrajee Piyarathna, Nagireddy Putluri, Helen Piwnica-Worms, Henry Charles Manning, Michael Andreeff, V Lokesh Battula

Faculty, Staff and Student Publications

Background: Metabolic stress resulting from nutrient deficiency is one of the hallmarks of a growing tumour. Here, we tested the hypothesis that metabolic stress induces breast cancer stem-like cell (BCSC) phenotype in triple-negative breast cancer (TNBC).

Methods: Flow cytometry for GD2 expression, mass spectrometry and Ingenuity Pathway Analysis for metabolomics, bioinformatics, in vitro tumorigenesis and in vivo models were used.

Results: Serum/glucose deprivation not only increased stress markers but also enhanced GD2+ BCSC phenotype and function in TNBC cells. Global metabolomics profiling identified upregulation of glutathione biosynthesis in GD2high cells, suggesting a role of glutamine in the BCSC phenotype. Cueing …

Zanubrutinib For Treatment-Naïve And Relapsed/Refractory Chronic Lymphocytic Leukaemia: Long-Term Follow-Up Of The Phase I/Ii Au-003 Study, Gavin Cull, Jan A Burger, Stephen Opat, David Gottlieb, Emma Verner, Judith Trotman, Paula Marlton, Javier Munoz, Patrick Johnston, David Simpson, Jennifer C Stern, Radha Prathikanti, Kenneth Wu, William Novotny, Jane Huang, Constantine S Tam

Faculty, Staff and Student Publications

The phase I/II AU-003 study in patients with treatment-naïve (TN) or relapsed/refractory (R/R) chronic lymphocytic leukaemia/small lymphocytic lymphoma demonstrated that zanubrutinib therapy results in clinically meaningful and durable responses with acceptable safety and tolerability. We report updated safety and efficacy data for 123 patients with a median follow-up of 47·2 months. Patients received zanubrutinib 160 mg twice daily (81 patients), 320 mg once daily (40), or 160 mg once daily (two). Discontinuations due to adverse events or disease progression were uncommon. The overall response rate (ORR) was 95·9% (TN, 100%; R/R, 95%) with 18·7% achieving complete response (CR). Ongoing response …

Fungi: Friend Or Foe? A Mycobiome Evaluation In Children With Autism And Gastrointestinal Symptoms, Jane Alookaran, Yuying Liu, Thomas A Auchtung, Amirali Tahanan, Manouchehr Hessabi, Parisa Asgarisabet, Mohammad H Rahbar, Nicole Y Fatheree, Deborah A Pearson, Rosleen Mansour, Melissa R Van Arsdall, Fernando Navarro, J Marc Rhoads

Faculty, Staff and Student Publications

Gastrointestinal (GI) symptoms often affect children with autism spectrum disorders (ASD) and GI symptoms have been associated with an abnormal fecal microbiome. There is limited evidence of Candida species being more prevalent in children with ASD. We enrolled 20 children with ASD and GI symptoms (ASD+GI), 10 children with ASD but no GI symptoms (ASD−GI), and 20 from typically developing (TD) children (TD) in this pilot study. Fecal mycobiome taxa were analyzed by ITS sequencing. GI symptoms (GI Severity Index (GSI)), behavioral symptoms (Social Responsiveness Scale −2 (SRS-2)), inflammation and fungal immunity (fecal calprotectin and serum dectin-1 (ELISA)) were evaluated. …

Nonjudgmental Acceptance: Associations With Substance-Related Cue Reactivity In Adults With Substance Use Disorders And Posttraumatic Stress, Anka A Vujanovic, Heather E Webber, Margaret C Wardle, Charles E Green, Scott D Lane, Joy M Schmitz

Faculty, Staff and Student Publications

The present investigation examined the predictive utility of nonjudgmental acceptance, a facet of mindfulness defined as the ability to remain aware and nonevaluative about internal experience, in terms of substance-related cue reactivity among adults with substance use disorders (SUD) and posttraumatic stress (PTS) symptomatology. We hypothesized that higher nonjudgmental acceptance, indexed via self-report, would predict higher levels of self-reported control over oneself and safety 'in the moment', broadly, and lower levels of substance-related craving in response to substance script cues. Effects were expected after subtracting reactivity to neutral script cues from each outcome rating. PTS severity was included as a …

Tissue-Targeted Crispr-Cas9-Mediated Genome Editing Of Multiple Homeologs In F0 Generation Xenopus Laevis Embryos, Mark E Corkins, Bridget D Delay, Rachel K Miller

Faculty, Staff and Student Publications

Xenopus laevis frogs are a powerful developmental model that enables studies combining classical embryology and molecular manipulation. Because of the large embryo size, ease of microinjection, and ability to target tissues through established fate maps, X. laevis have become the predominant amphibian research model. Given that their allotetraploid genome has complicated the generation of gene knockouts, strategies need to be established for efficient mutagenesis of multiple homeologs to evaluate gene function. Here we describe a protocol to utilize CRISPR-Cas9-mediated genome editing to target either single alleles or multiple alloalleles in F0 X. laevis embryos. A single guide (sg) RNA is …

Fungi: Friend Or Foe? A Mycobiome Evaluation In Children With Autism And Gastrointestinal Symptoms, Jane Alookaran, Yuying Liu, Thomas A Auchtung, Amirali Tahanan, Manouchehr Hessabi, Parisa Asgarisabet, Mohammad H Rahbar, Nicole Y Fatheree, Deborah A Pearson, Rosleen Mansour, Melissa R Van Arsdall, Fernando Navarro, J Marc Rhoads

Faculty, Staff and Student Publications

Gastrointestinal (GI) symptoms often affect children with autism spectrum disorders (ASD) and GI symptoms have been associated with an abnormal fecal microbiome. There is limited evidence of Candida species being more prevalent in children with ASD. We enrolled 20 children with ASD and GI symptoms (ASD + GI), 10 children with ASD but no GI symptoms (ASD - GI), and 20 from typically developing (TD) children in this pilot study. Fecal mycobiome taxa were analyzed by Internal Transcribed Spacer sequencing. GI symptoms (GI Severity Index [GSI]), behavioral symptoms (Social Responsiveness Scale -2 [SRS-2]), inflammation and fungal immunity (fecal calprotectin and …

Kaposiform Lymphangiomatosis Presenting With A Group A Streptococcus Pericardial Effusion, Taylor Koerner, Mehul D Patel, Vinay Pai, Gitanjali Indramohan

Faculty, Staff and Student Publications

A 4-year-old child was transferred to the paediatric intensive care unit with acute respiratory failure following 4 days of fever, nausea and vomiting. Chest X-ray on admission had an enlarged cardiac silhouette and transthoracic echo confirmed a large pericardial effusion. An emergent pericardiocentesis was performed at bedside which drained nearly 1000 mL of purulent fluid. Postdrainage course was complicated by acute systolic and diastolic heart failure, thrombocytopenia and acute renal failure. A chest CT and MRI were concerning for a diffuse mediastinal soft-tissue density, so the patient underwent interventional radiology-guided biopsy complicated by haemorrhage requiring mediastinal exploration and subtotal thymectomy. …

Wavelet Analysis Reveals Differential Lower Limb Muscle Activity Patterns Long After Anterior Cruciate Ligament Reconstruction, Payam Zandiyeh, Lauren R Parola, Braden C Fleming, Jillian E Beveridge

Faculty, Staff and Student Publications

The purpose of this study was to test whether differences in muscle activity patterns between anterior cruciate ligament-reconstructed patients (ACLR) and healthy controls could be detected 10 to 15 years post-surgery using a machine learning classification approach. Eleven ACLR subjects and 12 healthy controls were recruited from an ongoing prospective randomized clinical trial. Surface electromyography (EMG) signals were recorded from gastrocnemius medialis and lateralis, tibialis anterior, vastus medialis, rectus femoris, biceps femoris, and semitendinosus muscles. Muscle activity was analyzed using wavelet analysis and examined within four sub-phases of the hop test, as well as an average of the task as …

Perioperative Nivolumab Monotherapy Versus Nivolumab Plus Ipilimumab In Resectable Hepatocellular Carcinoma: A Randomised, Open-Label, Phase 2 Trial, Ahmed Omar Kaseb, Elshad Hasanov, Hop Sanderson Tran Cao, Lianchun Xiao, Jean-Nicolas Vauthey, Sunyoung S Lee, Betul Gok Yavuz, Yehia I Mohamed, Aliya Qayyum, Sonali Jindal, Fei Duan, Sreyashi Basu, Shalini S Yadav, Courtney Nicholas, Jing Jing Sun, Kanwal Pratap Singh Raghav, Asif Rashid, Kristen Carter, Yun Shin Chun, Ching-Wei David Tzeng, Divya Sakamuri, Li Xu, Ryan Sun, Vittorio Cristini, Laura Beretta, James C Yao, Robert A Wolff, James Patrick Allison, Padmanee Sharma

Faculty, Staff and Student Publications

BACKGROUND: Hepatocellular carcinoma has high recurrence rates after surgery; however, there are no approved standard-of-care neoadjuvant or adjuvant therapies. Immunotherapy has been shown to improve survival in advanced hepatocellular carcinoma; we therefore aimed to evaluate the safety and tolerability of perioperative immunotherapy in resectable hepatocellular carcinoma.

METHODS: In this single-centre, randomised, open-label, phase 2 trial, patients with resectable hepatocellular carcinoma were randomly assigned (1:1) to receive 240 mg of nivolumab intravenously every 2 weeks (for up to three doses before surgery at 6 weeks) followed in the adjuvant phase by 480 mg of nivolumab intravenously every 4 weeks for 2 …

Counterfactual Analysis Of Differential Comorbidity Risk Factors In Alzheimer’S Disease And Related Dementias, Yejin Kim, Kai Zhang, Sean I Savitz, Luyao Chen, Paul E Schulz, Xiaoqian Jiang

Faculty, Staff and Student Publications

Alzheimer’s disease and related dementias (ADRD) is a multifactorial disease that involves several different etiologic mechanisms with various comorbidities. There is also significant heterogeneity in the prevalence of ADRD across diverse demographics groups. Association studies on such heterogeneous comorbidity risk factors are limited in their ability to determine causation. We aim to compare counterfactual treatment effects of various comorbidity in ADRD in different racial groups (African Americans and Caucasians). We used 138,026 ADRD and 1:1 matched older adults without ADRD from nationwide electronic health records, which extensively cover a large population’s long medical history in breadth. We matched African Americans …

The Clock Modulator Nobiletin Mitigates Astrogliosis-Associated Neuroinflammation And Disease Hallmarks In An Alzheimer’S Disease Model, Marvin Wirianto, Chih-Yen Wang, Eunju Kim, Nobuya Koike, Ruben Gomez-Gutierrez, Kazunari Nohara, Gabriel Escobedo, Jong Min Choi, Chorong Han, Kazuhiro Yagita, Sung Yun Jung, Claudio Soto, Hyun Kyoung Lee, Rodrigo Morales, Seung-Hee Yoo, Zheng Chen

Faculty, Staff and Student Publications

Alzheimer's disease (AD) is a devastating neurodegenerative disorder, and there is a pressing need to identify disease-modifying factors and devise interventional strategies. The circadian clock, our intrinsic biological timer, orchestrates various cellular and physiological processes including gene expression, sleep, and neuroinflammation; conversely, circadian dysfunctions are closely associated with and/or contribute to AD hallmarks. We previously reported that the natural compound Nobiletin (NOB) is a clock-enhancing modulator that promotes physiological health and healthy aging. In the current study, we treated the double transgenic AD model mice, APP/PS1, with NOB-containing diets. NOB significantly alleviated β-amyloid burden in both the hippocampus and the …

Use Of The Deep Learning Approach To Measure Alveolar Bone Level, Chun-Teh Lee, Tanjida Kabir, Jiman Nelson, Sally Sheng, Hsiu-Wan Meng, Thomas E Van Dyke, Muhammad F Walji, Xiaoqian Jiang, Shayan Shams

Faculty, Staff and Student Publications

AIM: The goal was to use a deep convolutional neural network to measure the radiographic alveolar bone level to aid periodontal diagnosis.

MATERIALS AND METHODS: A deep learning (DL) model was developed by integrating three segmentation networks (bone area, tooth, cemento-enamel junction) and image analysis to measure the radiographic bone level and assign radiographic bone loss (RBL) stages. The percentage of RBL was calculated to determine the stage of RBL for each tooth. A provisional periodontal diagnosis was assigned using the 2018 periodontitis classification. RBL percentage, staging, and presumptive diagnosis were compared with the measurements and diagnoses made by the …

Current Surgical Indications For Non-Small-Cell Lung Cancer, Nathaniel Deboever, Kyle G Mitchell, Hope A Feldman, Tina Cascone, Boris Sepesi

Faculty, Staff and Student Publications

With recent strides made within the field of thoracic oncology, the management of NSCLC is evolving rapidly. Careful patient selection and timing of multi-modality therapy to permit the optimization of therapeutic benefit must be pursued. While chemotherapy and radiotherapy continue to have a role in the management of lung cancer, surgical therapy remains an essential component of lung cancer treatment in early, locally and regionally advanced, as well as in selected, cases of metastatic disease. Recent and most impactful advances in the treatment of lung cancer relate to the advent of immunotherapy and targeted therapy, molecular profiling, and predictive biomarker …