Life Sciences Commons^™

Deep-Learning-Based Generation Of Synthetic 6-Minute Mri From 2-Minute Mri For Use In Head And Neck Cancer Radiotherapy, Kareem A Wahid, Jiaofeng Xu, Dina El-Habashy, Yomna Khamis, Moamen Abobakr, Brigid Mcdonald, Nicolette O' Connell, Daniel Thill, Sara Ahmed, Christina Setareh Sharafi, Kathryn Preston, Travis C Salzillo, Abdallah S R Mohamed, Renjie He, Nathan Cho, John Christodouleas, Clifton D Fuller, Mohamed A Naser

Faculty, Staff and Student Publications

Background: Quick magnetic resonance imaging (MRI) scans with low contrast-to-noise ratio are typically acquired for daily MRI-guided radiotherapy setup. However, for patients with head and neck (HN) cancer, these images are often insufficient for discriminating target volumes and organs at risk (OARs). In this study, we investigated a deep learning (DL) approach to generate high-quality synthetic images from low-quality images.

Methods: We used 108 unique HN image sets of paired 2-minute T2-weighted scans (2mMRI) and 6-minute T2-weighted scans (6mMRI). 90 image sets (~20,000 slices) were used to train a 2-dimensional generative adversarial DL model that utilized 2mMRI as input and …

Head And Neck Cancer Primary Tumor Auto Segmentation Using Model Ensembling Of Deep Learning In Pet/Ct Images, Mohamed A Naser, Kareem A Wahid, Lisanne V Van Dijk, Renjie He, Moamen Abobakr Abdelaal, Cem Dede, Abdallah S R Mohamed, Clifton D Fuller

Faculty, Staff and Student Publications

Auto-segmentation of primary tumors in oropharyngeal cancer using PET/CT images is an unmet need that has the potential to improve radiation oncology workflows. In this study, we develop a series of deep learning models based on a 3D Residual Unet (ResUnet) architecture that can segment oropharyngeal tumors with high performance as demonstrated through internal and external validation of large-scale datasets (training size = 224 patients, testing size = 101 patients) as part of the 2021 HECKTOR Challenge. Specifically, we leverage ResUNet models with either 256 or 512 bottleneck layer channels that demonstrate internal validation (10-fold cross-validation) mean Dice similarity coefficient …

Anatomy And Function Of Ventral Tegmental Area Glutamate Neurons, Jing Cai, Qingchun Tong

Faculty, Staff and Student Publications

The ventral tegmental area (VTA) is well known for regulating reward consumption, learning, memory, and addiction behaviors through mediating dopamine (DA) release in downstream regions. Other than DA neurons, the VTA is known to be heterogeneous and contains other types of neurons, including glutamate neurons. In contrast to the well-studied and established functions of DA neurons, the role of VTA glutamate neurons is understudied, presumably due to their relatively small quantity and a lack of effective means to study them. Yet, emerging studies have begun to reveal the importance of glutamate release from VTA neurons in regulating diverse behavioral repertoire …

Evolutionary Action Score Of Tp53 Analysis In Pathologically High-Risk Human Papillomavirus-Negative Head And Neck Cancer From A Phase 2 Clinical Trial: Nrg Oncology Radiation Therapy Oncology Group 0234, Chieko Michikawa, Pedro A Torres-Saavedra, Natalie L Silver, Paul M Harari, Merrill S Kies, David I Rosenthal, Quynh-Thu Le, Richard C Jordan, Dzifa Y Duose, Saradhi Mallampati, Sanchit Trivedi, Rajyalakshmi Luthra, Ignacio I Wistuba, Abdullah A Osman, Olivier Lichtarge, Robert L Foote, Upendra Parvathaneni, D Neil Hayes, Curtis R Pickering, Jeffrey N Myers

Faculty, Staff and Student Publications

PURPOSE: An evolutionary action scoring algorithm (EAp53) based on phylogenetic sequence variations stratifies patients with head and neck squamous cell carcinoma (HNSCC) bearing

METHODS AND MATERIALS: Eighty-one resection samples from patients treated surgically for stage III or IV human papillomavirus-negative HNSCC with high-risk pathologic features, who received either radiation therapy + cetuximab + cisplatin (cisplatin) or radiation therapy + cetuximab + docetaxel (docetaxel) as adjuvant treatment in a phase 2 study were subjected to

RESULTS: At a median follow-up of 9.8 years, there was a significant interaction between EAp53 group and treatment for overall survival (

CONCLUSIONS: The docetaxel arm …

Cancer Treatment-Induced Nad+ Depletion In Premature Senescence And Late Cardiovascular Complications, Priyanka Banerjee, Elizabeth A Olmsted-Davis, Anita Deswal, Minh Th Nguyen, Efstratios Koutroumpakis, Nicholas L Palaskas, Steven H Lin, Sivareddy Kotla, Cielito Reyes-Gibby, Sai-Ching J Yeung, Syed Wamique Yusuf, Momoko Yoshimoto, Michihiro Kobayashi, Bing Yu, Keri Schadler, Joerg Herrmann, John P Cooke, Abhishek Jain, Eduardo Chini, Nhat-Tu Le, Jun-Ichi Abe

Faculty, Staff and Student Publications

Numerous studies have revealed the critical role of premature senescence induced by various cancer treatment modalities in the pathogenesis of aging-related diseases. Senescence-associated secretory phenotype (SASP) can be induced by telomere dysfunction. Telomeric DNA damage response induced by some cancer treatments can persist for months, possibly accounting for long-term sequelae of cancer treatments. Telomeric DNA damage-induced mitochondrial dysfunction and increased reactive oxygen species production are hallmarks of premature senescence. Recently, we reported that the nucleus-mitochondria positive feedback loop formed by p90 ribosomal S6 kinase (p90RSK) and phosphorylation of S496 on ERK5 (a unique member of the mitogen-activated protein kinase family …

Comparison Of Three Exercise Interventions With And Without Gemcitabine Treatment On Pancreatic Tumor Growth In Mice: No Impact On Tumor Infiltrating Lymphocytes, Priti Gupta, Charles F Hodgman, Claudia Alvarez-Florez, Keri L Schadler, Melissa M Markofski, Daniel P O'Connor, Emily C Lavoy

Faculty, Staff and Student Publications

Exercise has been shown to slow pancreatic tumor growth, but whether exercise interventions of differing volume or intensity yield differential effects on tumor outcomes is unknown. In this study, we compared three exercise training interventions implemented with and without chemotherapy on pancreatic tumor growth in mice. Methods: Male C57BL/6 mice (6-8 weeks old) were subcutaneously inoculated with pancreatic ductal adenocarcinoma tumor cells (PDAC 4662). Upon tumor detection, mice received gemcitabine 15 mg/kg intraperitoneally 3 days/week and were assigned to exercise: high volume continuous exercise (HVCE), low volume continuous exercise (LVCE), high intensity interval training (HIIT), or sedentary (SED). HVCE ran …

Semiparametric Copula-Based Regression Modeling Of Semi-Competing Risks Data, Hong Zhu, Yu Lan, Jing Ning, Yu Shen

Faculty, Staff and Student Publications

Semi-competing risks data often arise in medical studies where the terminal event (e.g., death) censors the non-terminal event (e.g., cancer recurrence), but the non-terminal event does not prevent the subsequent occurrence of the terminal event. This article considers regression modeling of semi-competing risks data to assess the covariate effects on the respective non-terminal and terminal event times. We propose a copula-based framework for semi-competing risks regression with time-varying coefficients, where the dependence between the non-terminal and terminal event times is characterized by a copula and the time-varying covariate effects are imposed on two marginal regression models. We develop a two-stage …

Impact Of Psychosocial, Behavioral And Lifestyle Factors On Subjective Cognitive Complaints And Perceived Quality Of Life In A Large Cohort Of Italian Breast Cancer Patients, Thomas West, Corrado Cavallero, Rita Ceccherini, Silva Foladore, Daniele Generali, Francesco Versace, Bruna Scaggiante

Faculty, Staff and Student Publications

The impact of psychosocial and behavioral factors on Cancer Related Cognitive Impairment manifestations is still under debate. Study's purpose is to determine the prevalence rate of cancer related cognitive impairment in a cohort of Italian breast cancer patients and to evaluate the implication of specific behavioral factors. For these purposes, a total of 233 women (106 breast cancer patients and 127 age-matched controls without oncological diagnosis) completed a questionnaire investigating cognitive functionality (FACT-Cog v3.0), sociodemographic characteristics, clinical information, psychosocial and behavioral factors (cognitive reserve, sleep quality, dietary habits, physical activity). The results indicated a higher prevalence rate of subjective cognitive …

Single-Incision Laparoscopic Splenectomy In Children With Massive Splenomegaly: A Prospective, Monocentric Pilot Study, Congjun Wang, Cheng Su, Chao Chen, Xianming Tang, Hong Wang, Wei Li, Yanqiang Li, Qiang Liu, Peng Chen, Yong Li, Yige Luo

Faculty, Staff and Student Publications

BACKGROUND: Single-incision laparoscopic splenectomy (SILS) remains a challenging procedure because of the technical difficulty. In this prospective study, we aimed to evaluate the efficacy and safety of SILS in children with massive splenomegaly.

METHODS: Pediatric patients with massive splenomegaly were recruited for SILS in a university-affiliated hospital. The data on patient demographics, clinical features, operative variables, and perioperative outcomes were collected prospectively and analyzed. According to the different surgical instruments, the patients were randomly assigned into two groups: the SILS with straight surgical instrument (SILS-S) group and the SILS with curved surgical instrument (SILS-C) group. A two-group comparative analysis was …

Dose Accumulation For Mr-Guided Adaptive Radiotherapy: From Practical Considerations To State-Of-The-Art Clinical Implementation, Brigid A Mcdonald, Cornel Zachiu, John Christodouleas, Mohamed A Naser, Mark Ruschin, Jan-Jakob Sonke, Daniela Thorwarth, Daniel Létourneau, Neelam Tyagi, Tony Tadic, Jinzhong Yang, X Allen Li, Uffe Bernchou, Daniel E Hyer, Jeffrey E Snyder, Edyta Bubula-Rehm, Clifton D Fuller, Kristy K Brock

Faculty, Staff and Student Publications

MRI-linear accelerator (MR-linac) devices have been introduced into clinical practice in recent years and have enabled MR-guided adaptive radiation therapy (MRgART). However, by accounting for anatomical changes throughout radiation therapy (RT) and delivering different treatment plans at each fraction, adaptive radiation therapy (ART) highlights several challenges in terms of calculating the total delivered dose. Dose accumulation strategies-which typically involve deformable image registration between planning images, deformable dose mapping, and voxel-wise dose summation-can be employed for ART to estimate the delivered dose. In MRgART, plan adaptation on MRI instead of CT necessitates additional considerations in the dose accumulation process because MRI …

Allogeneic Hematopoietic Cell Transplantation For Patients With Blastic Plasmacytoid Dendritic Cell Neoplasm (Bpdcn), Qaiser Bashir, Denái R Milton, Uday R Popat, Partow Kebriaei, Chitra Hosing, Issa F Khouri, Katayoun Rezvani, Yago Nieto, Betul Oran, Samer A Srour, Neeraj Y Saini, Amanda L Olson, Sairah Ahmed, Gheath Al-Atrash, Gabriela Rondon, Marina Y Konopleva, Richard E Champlin, Elizabeth J Shpall, Muzaffar H Qazilbash, Naveen Pemmaraju

Faculty, Staff and Student Publications

Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) is an aggressive hematological malignancy; however, some patients achieve durable remission with allogeneic hematopoietic cell transplantation (allo-HCT). We report on all 17 patients with BPDCN who underwent allo-HCT at our center between 2000 and 2020. The median age was 39 (18-67) years. All (n = 16, 94%), except one patient, had systemic disease involving bone marrow and/or other organs. Ten patients (59%) were in first complete remission (CR1) at allo-HCT. The donor source was matched related or unrelated in ten (59%) and alternate donor in seven (41%) patients. Five (31%) patients developed acute graft-versus-host …

Fadu Head And Neck Squamous Cell Carcinoma Induces Hyperexcitability Of Primary Sensory Neurons In An In Vitro Coculture Model, Megan L Uhelski, Aysegul Gorur, Ted Shi, German Corrales, Kim N Du, Yan Li, Moran Amit, Claudio E Tatsui, Laurence D Rhines, Patrick M Dougherty, Juan P Cata

Faculty, Staff and Student Publications

Introduction: Currently, cancer pain is viewed as a process orchestrated by the release of pronociceptive molecules and the invasion of neural structures, referred to as perineural invasion (PNI). Cancer pain resulting from PNI is well-documented, but the mechanisms leading to peripheral sensitization because of tumor growth are not fully known.

Methods: A retrospective study was used to examine how the use of anti-inflammatory medications affected preoperative pain in patients with oral squamous cell carcinoma cancer. We then used an in vitro coculture model in which dorsal root ganglion (DRG) neurons were incubated together with Fadu human head and neck squamous …

Targeting Mcl-1 Dysregulates Cell Metabolism And Leukemia-Stroma Interactions And Resensitizes Acute Myeloid Leukemia To Bcl-2 Inhibition, Bing Z Carter, Po Yee Mak, Wenjing Tao, Marc Warmoes, Philip L Lorenzi, Duncan Mak, Vivian Ruvolo, Lin Tan, Justin Cidado, Lisa Drew, Michael Andreeff

Faculty, Staff and Student Publications

MCL-1 and BCL-2 are both frequently overexpressed in acute myeloid leukemia and critical for the survival of acute myeloid leukemia cells and acute myeloid leukemia stem cells. MCL-1 is a key factor in venetoclax resistance. Using genetic and pharmacological approaches, we discovered that MCL-1 regulates leukemia cell bioenergetics and carbohydrate metabolisms, including the TCA cycle, glycolysis and pentose phosphate pathway and modulates cell adhesion proteins and leukemia-stromal interactions. Inhibition of MCL-1 sensitizes to BCL-2 inhibition in acute myeloid leukemia cells and acute myeloid leukemia stem/progenitor cells, including those with intrinsic and acquired resistance to venetoclax through cooperative release of pro-apoptotic …

Application Of Artificial Intelligence To Plasma Metabolomics Profiles To Predict Response To Neoadjuvant Chemotherapy In Triple-Negative Breast Cancer, Ehsan Irajizad, Ranran Wu, Jody Vykoukal, Eunice Murage, Rachelle Spencer, Jennifer B Dennison, Stacy Moulder, Elizabeth Ravenberg, Bora Lim, Jennifer Litton, Debu Tripathym, Vicente Valero, Senthil Damodaran, Gaiane M Rauch, Beatriz Adrada, Rosalind Candelaria, Jason B White, Abenaa Brewster, Banu Arun, James P Long, Kim Anh Do, Sam Hanash, Johannes F Fahrmann

Faculty, Staff and Student Publications

There is a need to identify biomarkers predictive of response to neoadjuvant chemotherapy (NACT) in triple-negative breast cancer (TNBC). We previously obtained evidence that a polyamine signature in the blood is associated with TNBC development and progression. In this study, we evaluated whether plasma polyamines and other metabolites may identify TNBC patients who are less likely to respond to NACT. Pre-treatment plasma levels of acetylated polyamines were elevated in TNBC patients that had moderate to extensive tumor burden (RCB-II/III) following NACT compared to those that achieved a complete pathological response (pCR/RCB-0) or had minimal residual disease (RCB-I). We further applied …

Glioma And The Gut-Brain Axis: Opportunities And Future Perspectives, Antonio Dono, Jack Nickles, Ana G Rodriguez-Armendariz, Braden C Mcfarland, Nadim J Ajami, Leomar Y Ballester, Jennifer A Wargo, Yoshua Esquenazi

Faculty, Staff and Student Publications

The gut-brain axis has presented a valuable new dynamic in the treatment of cancer and central nervous system (CNS) diseases. However, little is known about the potential role of this axis in neuro-oncology. The goal of this review is to highlight potential implications of the gut-brain axis in neuro-oncology, in particular gliomas, and future areas of research. The gut-brain axis is a well-established biochemical signaling axis that has been associated with various CNS diseases. In neuro-oncology, recent studies have described gut microbiome differences in tumor-bearing mice and glioma patients compared to controls. These differences in the composition of the microbiome …

A Narrative Review On Invasive Brain Stimulation For Treatment-Resistant Depression, Manoj P Dandekar, Alexandre P Diaz, Ziaur Rahman, Ritele H Silva, Ziad Nahas, Scott Aaronson, Sudhakar Selvaraj, Albert J Fenoy, Marsal Sanches, Jair C Soares, Patricio Riva-Posse, Joao Quevedo

Faculty, Staff and Student Publications

While most patients with depression respond to pharmacotherapy and psychotherapy, about one-third will present treatment resistance to these interventions. For patients with treatment-resistant depression (TRD), invasive neurostimulation therapies such as vagus nerve stimulation, deep brain stimulation, and epidural cortical stimulation may be considered. We performed a narrative review of the published literature to identify papers discussing clinical studies with invasive neurostimulation therapies for TRD. After a database search and title and abstract screening, relevant English-language articles were analyzed. Vagus nerve stimulation, approved by the U.S. Food and Drug Administration as a TRD treatment, may take several months to show therapeutic …

Harmonization Of Multi-Scanner In Vivo Magnetic Resonance Spectroscopy: Enigma Consortium Task Group Considerations, Ashley D Harris, Houshang Amiri, Mariana Bento, Ronald Cohen, Christopher R K Ching, Christina Cudalbu, Emily L Dennis, Arne Doose, Stefan Ehrlich, Ivan I Kirov, Ralf Mekle, Georg Oeltzschner, Eric Porges, Roberto Souza, Friederike I Tam, Brian Taylor, Paul M Thompson, Yann Quidé, Elisabeth A Wilde, John Williamson, Alexander P Lin, Brenda Bartnik-Olson

Faculty, Staff and Student Publications

Magnetic resonance spectroscopy is a powerful, non-invasive, quantitative imaging technique that allows for the measurement of brain metabolites that has demonstrated utility in diagnosing and characterizing a broad range of neurological diseases. Its impact, however, has been limited due to small sample sizes and methodological variability in addition to intrinsic limitations of the method itself such as its sensitivity to motion. The lack of standardization from a data acquisition and data processing perspective makes it difficult to pool multiple studies and/or conduct multisite studies that are necessary for supporting clinically relevant findings. Based on the experience of the ENIGMA MRS …

Landmark Mediation Survival Analysis Using Longitudinal Surrogate, Jie Zhou, Xun Jiang, H Amy Xia, Brian P Hobbs, Peng Wei

Faculty, Staff and Student Publications

Clinical cancer trials are designed to collect radiographic measurements of each patient's baseline and residual tumor burden at regular intervals over the course of study. For solid tumors, the extent of reduction in tumor size following treatment is used as a measure of a drug's antitumor activity. Statistical estimation of treatment efficacy routinely reduce the longitudinal assessment of tumor burden to a binary outcome describing the presence versus absence of an objective tumor response as defined by RECIST criteria. The objective response rate (ORR) is the predominate method for evaluating an experimental therapy in a single-arm trial. Additionally, ORR is …

Checkpoint Inhibitors As Immunotherapy For Fungal Infections: Promises, Challenges, And Unanswered Questions, Sebastian Wurster, Stephanie S Watowich, Dimitrios P Kontoyiannis

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Opportunistic fungal infections have high mortality in patients with severe immune dysfunction. Growing evidence suggests that the immune environment of invasive fungal infections and cancers share common features of immune cell exhaustion through activation of immune checkpoint pathways. This observation gave rise to several preclinical studies and clinical case reports describing blockade of the Programmed Cell Death Protein 1 and Cytotoxic T-Lymphocyte Antigen 4 immune checkpoint pathways as an adjunct immune enhancement strategy to treat opportunistic fungal infections. The first part of this review summarizes the emerging evidence for contributions of checkpoint pathways to the immunopathology of fungal sepsis, opportunistic …

An Autoencoder-Based Deep Learning Method For Genotype Imputation, Meng Song, Jonathan Greenbaum, Joseph Luttrell, Weihua Zhou, Chong Wu, Zhe Luo, Chuan Qiu, Lan Juan Zhao, Kuan-Jui Su, Qing Tian, Hui Shen, Huixiao Hong, Ping Gong, Xinghua Shi, Hong-Wen Deng, Chaoyang Zhang

Faculty, Staff and Student Publications

Genotype imputation has a wide range of applications in genome-wide association study (GWAS), including increasing the statistical power of association tests, discovering trait-associated loci in meta-analyses, and prioritizing causal variants with fine-mapping. In recent years, deep learning (DL) based methods, such as sparse convolutional denoising autoencoder (SCDA), have been developed for genotype imputation. However, it remains a challenging task to optimize the learning process in DL-based methods to achieve high imputation accuracy. To address this challenge, we have developed a convolutional autoencoder (AE) model for genotype imputation and implemented a customized training loop by modifying the training process with a …

Clinical Implementation And Initial Experience With A 15 Tesla Mr-Linac For Mr-Guided Radiation Therapy For Gynecologic Cancer: An R-Ideal Stage 1 And 2a First In Humans Feasibility Study Of New Technology Implementation, David S Lakomy, Jinzhong Yang, Sastry Vedam, Jihong Wang, Belinda Lee, Angela Sobremonte, Pamela Castillo, Neil Hughes, Mustefa Mohammedsaid, Anuja Jhingran, Ann H Klopp, Seungtaek Choi, C David Fuller, Lilie L Lin

Faculty, Staff and Student Publications

PURPOSE: Magnetic resonance imaging-guided linear accelerator systems (MR-linacs) can facilitate the daily adaptation of radiation therapy plans. Here, we report our early clinical experience using a MR-linac for adaptive radiation therapy of gynecologic malignancies.

METHODS AND MATERIALS: Treatments were planned with an Elekta Monaco v5.4.01 and delivered by a 1.5 Tesla Elekta Unity MR-linac. The system offers a choice of daily adaptation based on either position (ATP) or shape (ATS) of the tumor and surrounding normal structures. The ATS approach has the option of manually editing the contours of tumors and surrounding normal structures before the plan is adapted. Here, …

Neoadjuvant Checkpoint Inhibitor Immunotherapy For Resectable Mucosal Melanoma, Joel Ho, Jane Mattei, Michael Tetzlaff, Michelle D Williams, Michael A Davies, Adi Diab, Isabella C Glitza Oliva, Jennifer Mcquade, Sapna P Patel, Hussein Tawbi, Michael K Wong, Sarah B Fisher, Ehab Hanna, Emily Z Keung, Merrick Ross, Roi Weiser, Shirley Y Su, Michael Frumovitz, Larissa A Meyer, Amir Jazaeri, Curtis A Pettaway, B Ashleigh Guadagnolo, Andrew J Bishop, Devarati Mitra, Ahsan Farooqi, Roland Bassett, Silvana Faria, Priyadharsini Nagarajan, Rodabe N Amaria

Faculty, Staff and Student Publications

BACKGROUND: Neoadjuvant checkpoint inhibition (CPI) has recently demonstrated impressive outcomes in patients with stage 3 cutaneous melanoma. However, the safety, efficacy, and outcome of neoadjuvant CPI in patients with mucosal melanoma (MM) are not well studied as MM is a rare melanoma subtype. CPI such as combination nivolumab and ipilimumab achieves response rates of 37-43% in unresectable or metastatic MM but there is limited data regarding the efficacy of these agents in the preoperative setting. We hypothesize that neoadjuvant CPI is a safe and feasible approach for patients with resectable MM.

METHOD: Under an institutionally approved protocol, we identified adult …

Defective Dna Polymerase Beta Invoke A Cytosolic Dna Mediated Inflammatory Response, Shengyuan Zhao, Julia A Goewey Ruiz, Manu Sebastian, Dawit Kidane

Faculty, Staff and Student Publications

Base excision repair (BER) has evolved to maintain the genomic integrity of DNA following endogenous and exogenous agent induced DNA base damage. In contrast, aberrant BER induces genomic instability, promotes malignant transformation and can even trigger cancer development. Previously, we have shown that deoxyribo-5'-phosphate (dRP) lyase deficient DNA polymerase beta (POLB) causes replication associated genomic instability and sensitivity to both endogenous and exogenous DNA damaging agents. Specifically, it has been established that this loss of dRP lyase function promotes inflammation associated gastric cancer. However, the way that aberrant POLB impacts the immune signaling and inflammatory responses is still unknown. Here …

Association Of Adenotonsillar Disease And Adenotonsillectomy With The Development Of Vitiligo: A Nationwide Population-Based Cohort Study, Jong Seung Kim, Min Gyu Lee, Sang-Kyung Lee, Sang-Woo Yeom, Min-Gu Kang, Jong Hwan Lee, Il-Jae Lee, Jin Park, Seok-Kweon Yun, Kyung-Hwa Nam

Faculty, Staff and Student Publications

BACKGROUND: Vitiligo is a common acquired skin depigmentation disorder and is associated with various other autoimmune diseases which include thyroid disease and rheumatoid arthritis. Similarly, adenotonsillar disease (ATD) may induce inflammatory or autoimmune diseases in other organs which include the skin. However, the influence of ATD on the development of vitiligo has not been studied.

OBJECTIVES: To determine the association between ATD and adenotonsillectomy, and the development of vitiligo.

DESIGN AND METHODS: Using data from the National Health Insurance Service database, patients diagnosed with ATD between 2008 and 2010 were included in the study. We performed two rounds of 1:1 …

Multiplexed Engineering And Precision Gene Editing In Cellular Immunotherapy, Alexander Biederstädt, Gohar Shahwar Manzar, May Daher

Faculty, Staff and Student Publications

The advent of cellular immunotherapy in the clinic has entirely redrawn the treatment landscape for a growing number of human cancers. Genetically reprogrammed immune cells, including chimeric antigen receptor (CAR)-modified immune effector cells as well as T cell receptor (TCR) therapy, have demonstrated remarkable responses across different hard-to-treat patient populations. While these novel treatment options have had tremendous success in providing long-term remissions for a considerable fraction of treated patients, a number of challenges remain. Limited

Serum Gamma Glutamyltransferase (Ggt) In Coronary Artery Disease: Exploring The Asian Indian Connection, Kunal K Singh, Aditya Kapoor, Roopali Khanna, Ankit Sahu, Vishwas Kapoor, Sudeep Kumar, Naveen Garg, Satyendra Tewari, Pravin Goel

Faculty, Staff and Student Publications

BACKGROUND: There is a need to identify novel markers for CAD, independent of traditional CV risk factors. One of these is gamma-glutamyl transferase (GGT), a marker of increased oxidative stress. Given the high prevalence of CAD in Asian Indians, the link of GGT and CAD in them needs to be studied.

AIM: To assess GGT in patients with angiographically documented CAD.

METHODS AND RESULTS: Two hundred patients aged 58.1 ± 9.95 years, 73% males, hypertension 56%, diabetes 40% were included. Mean GGT was 63.6 ± 44.33 (10–269 U/L). The levels of GGT progressively increased in those with single/double or triple-vessel …

Association Of Proton Pump Inhibitor Use With Survival Outcomes In Cancer Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review And Meta-Analysis, Baoqing Chen, Chen Yang, Mihnea P Dragomir, Dongmei Chi, Wenyan Chen, David Horst, George A Calin, Qiaoqiao Li

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Background: Proton pump inhibitors (PPIs) have been shown to regulate the gut microbiome and affect the response to immune checkpoint inhibitors (ICIs). Contradictory results on survival have been observed in patients concomitantly treated with ICIs and PPIs. We performed a systematic review and meta-analysis to determine the association between PPI use and survival outcomes in ICI-treated cancer patients.

Methods: EMBASE, MEDLINE/PubMed, Cochrane Library databases, and major oncology conference proceedings were searched. Studies comparing overall survival (OS) and progression-free survival (PFS) between PPI-treated and PPI-free groups of ICI-treated cancer patients were included. Data regarding study and patient characteristics, ICI and PPI …

Translating Mentoring Interventions Research Into Practice: Evaluation Of An Evidence-Based Workshop For Research Mentors On Developing Trainees’ Scientific Communication Skills, Erin K Dahlstrom, Christine Bell, Shine Chang, Hwa Young Lee, Cheryl B Anderson, Annie Pham, Christine Maidl Pribbenow, Carrie A Cameron

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A key part of keeping doctoral and postdoctoral trainees in STEM research careers is mentoring. Our previous research indicates that mentoring trainees in scientific communication (SC) skill development increases research career intention through two social-cognitive constructs, self-efficacy in and outcome expectations for acquiring SC skills, as well as science identity. While many mentor training interventions exist, no programs focus on developing SC skills specifically. The "Scientific Communication Advances Research Excellence" (SCOARE) program trains mentors to address trainee scientific communication (SC) skill development as an innovative approach to increase trainee research career persistence. The SCOARE training is a half-day workshop for …

Pathogenic Tau Accelerates Aging-Associated Activation Of Transposable Elements In The Mouse Central Nervous System, Paulino Ramirez, Gabrielle Zuniga, Wenyan Sun, Adrian Beckmann, Elizabeth Ochoa, Sarah L Devos, Bradley Hyman, Gabriel Chiu, Ethan R Roy, Wei Cao, Miranda Orr, Virginie Buggia-Prevot, William J Ray, Bess Frost

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Transposable elements comprise almost half of the mammalian genome. A growing body of evidence suggests that transposable element dysregulation accompanies brain aging and neurodegenerative disorders, and that transposable element activation is neurotoxic. Recent studies have identified links between pathogenic forms of tau, a protein that accumulates in Alzheimer's disease and related "tauopathies," and transposable element-induced neurotoxicity. Starting with transcriptomic analyses, we find that age- and tau-induced transposable element activation occurs in the mouse brain. Among transposable elements that are activated at the RNA level in the context of brain aging and tauopathy, we find that the endogenous retrovirus (ERV) class …

Research Career Intentions Among Non-Native English-Speaking Graduate And Postdoctoral Trainees In Stem-Results From Cross-Sectional And Longitudinal Studies, Hwa Young Lee, Shine Chang, Cheryl B Anderson, Erin K Dahlstrom, Carrie Cameron

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International graduate trainees, many of whom are non-native English-speaking (L2) trainees, comprise more than half of graduate-level trainees in STEM, but little is known regarding factors that influence their career intentions, especially those that foster their growth as scientists to achieve their full potential in research. Thus, the purpose of our studies was to examine the relationship between L2 status and contextual factors that help shape the learning experiences and plans for research-focused careers. Study 1 collected cross-sectional survey data from doctoral and postdoctoral trainees (N=510) from research institutes in the Texas Medical Center in Houston. We examined which factors …