Medicine and Health Sciences Commons^™

Dek::Aff2 Fusion-Associated Squamous Cell Carcinoma: A Case Series With Literature Review On An Emerging And Challenging Entity, Sara E Amin, James S Lewis, Julia A Bridge, Jen-Fan Hang, Udit Naik, Justin A Bishop, Karan Saluja

Faculty, Staff and Student Publications

Purpose: DEK::AFF2 fusion-associated squamous cell carcinoma (DEK::AFF2 SCC), also reported in the literature as low-grade papillary sinonasal (Schneiderian) carcinoma (LGPSC), is a rare, primarily bland-appearing, but locally aggressive neoplasm. Morphologically, these tumors can closely resemble sinonasal papilloma (SP), especially on small or limited biopsy, often leading to misdiagnosis. DEK::AFF2 SCC is devoid of the underlying mutually exclusive EGFR or KRAS driver mutations of SP, suggesting it may represent a distinct unique entity.

Methods: In this study, we conducted a retrospective search of "unusual" SP reported either as atypical, dysplastic, or suspicious for malignant transformation at our institution in the last …

Strategic Stabilization Of Arousal Boosts Sustained Attention, Jan Willem De Gee, Zakir Mridha, Marisa Hudson, Yanchen Shi, Hannah Ramsaywak, Spencer Smith, Nishad Karediya, Matthew Thompson, Kit Jaspe, Hong Jiang, Wenhao Zhang, Matthew J Mcginley

Duncan NRI Faculty and Staff Publications

Arousal and motivation interact to profoundly influence behavior. For example, experience tells us that we have some capacity to control our arousal when appropriately motivated, such as staying awake while driving a motor vehicle. However, little is known about how arousal and motivation jointly influence decision computations, including if and how animals, such as rodents, adapt their arousal state to their needs. Here, we developed and show results from an auditory, feature-based, sustained-attention task with intermittently shifting task utility. We use pupil size to estimate arousal across a wide range of states and apply tailored signal detection theoretic, hazard function …

Financial Toxicity In Breast Cancer Patients Receiving Regional Nodal Irradiation: Variation By Cancer Subtype, Grace L Smith, Benjamin D Smith, Chi-Fang Wu, Simona F Shaitelman, Mariana Chavez-Macgregor, Rashmi Murthy, Kelsey Kaiser, Kimberly S Ku, Julia J Shi, Sanjay S Shete, Ying-Shiuan Chen, Robert J Volk, Sharon H Giordano, Ya-Chen T Shih, Karen E Hoffman

Faculty, Staff and Student Publications

BACKGROUND: We evaluated sociodemographic and clinical predictors of financial toxicity (FT) among patients with breast cancer with higher risk clinical factors warranting regional nodal irradiation (RNI).

METHODS: Among 183 participants in a clinical trial of conventional vs. hypofractionated treatment with RNI, 125 (68 %) completed a pilot survey of FT measured using the validated Economic Strain and Resilience in Cancer (ENRICh) instrument, scored from 0 (minimal) to 10 (severe) FT. Associations with predictors were evaluated using Pearson correlation coefficients and Kruskal Wallis, Mann-Whitney U, and Jonckheere-Terpstra tests. Predictors of severe FT (ENRICh≥5) were tested using multivariable logistic regression with odds …

Examining Management And Employees' Perceptions Of Occupational Heat Exposure And The Effectiveness Of A Heat Stress Prevention Intervention On Safety And Well-Being Among Natural Gas Construction Workers: A Qualitative Field-Based Study, Muinat Abolore Idris, Christine Markham, Kristina D Mena, William B Perkison

Faculty, Staff and Student Publications

BACKGROUND: Numerous risk factors have been identified as significantly influencing outdoor workers' risk for heat stress and heat-related conditions, impacting their health, well-being, and productivity. However, the specific effects of these factors on construction workers' safety, health, and well-being remain under-researched. With climate change increasing temperatures, assessing heat stress among construction workers is imperative.

OBJECTIVE: To identify the barriers and facilitators influencing the safety of natural gas construction workers and evaluate an implemented heat stress intervention.

METHODS: In the summer of 2023, two semi-structured interviews and six focus groups were conducted with twenty-one stakeholders at a Texas natural gas construction …

A Bayesian Semi-Parametric Scalar-On-Function Regression With Measurement Error Using Instrumental Variables, Roger S Zoh, Yuanyuan Luan, Lan Xue, David B Allison, Carmen D Tekwe

Children’s Nutrition Research Center Staff Publications

Wearable devices such as the ActiGraph are now commonly used in research to monitor or track physical activity. This trend corresponds with the growing need to assess the relationships between physical activity and health outcomes, such as obesity, accurately. Device-based physical activity measures are best treated as functions when assessing their associations with scalar-valued outcomes such as body mass index. Scalar-on-function regression (SoFR) is a suitable regression model in this setting. Most estimation approaches in SoFR assume that the measurement error in functional covariates is white noise. Violating this assumption can lead to underestimating model parameters. There are limited approaches …

Implementation Of Healthy Heart Ambassador To Improve Blood Pressure Control At Community Health Centers In Texas, Natalia I Heredia, Ella R Garza, Fernanda Velasco-Huerta, Tracy L Swoboda, Pierre Fwelo, Patenne D Mathews, Maria E Fernandez

Faculty, Staff and Student Publications

BACKGROUND: Hypertension is one of the most prevalent chronic diseases in the United States and can increase a person's risk of stroke and other cardiovascular complications. Yet only 1 in 4 people with high blood pressure in the United States have their blood pressure managed. To improve hypertension control, we supported 9 health centers in Texas with the implementation of the Healthy Heart Ambassador Blood Pressure Self-Monitoring (HHA) Program.

METHODS: We provided health center training using the HHA Program Facilitation Training Guide, recorded barriers to implementing the HHA program, and employed strategies to overcome those barriers.

RESULTS: There were 68 …

Tumor-Infiltrating Nerves Functionally Alter Brain Circuits And Modulate Behavior In A Mouse Model Of Head-And-Neck Cancer, Jeffrey Barr, Austin Walz, Anthony C Restaino, Moran Amit, Sarah M Barclay, Elisabeth G Vichaya, William C Spanos, Robert Dantzer, Sebastien Talbot, Paola D Vermeer

Faculty, Staff and Student Publications

Cancer patients often experience changes in mental health, prompting an exploration into whether nerves infiltrating tumors contribute to these alterations by impacting brain functions. Using a mouse model for head and neck cancer and neuronal tracing, we show that tumor-infiltrating nerves connect to distinct brain areas. The activation of this neuronal circuitry altered behaviors (decreased nest-building, increased latency to eat a cookie, and reduced wheel running). Tumor-infiltrating nociceptor neurons exhibited heightened calcium activity and brain regions receiving these neural projections showed elevated Fos as well as increased calcium responses compared to non-tumor-bearing counterparts. The genetic elimination of nociceptor neurons decreased …

Applying Deep Learning With Convolutional Neural Networks To Laryngoscopic Imaging For Automated Segmentation And Classification Of Vocal Cord Leukoplakia, Ming Xiong, Jia-Wei Luo, Jia Ren, Juan-Juan Hu, Lan Lan, Ying Zhang, Dan Lv, Xiao-Bo Zhou, Hui Yang

Faculty, Staff and Student Publications

Objectives: Vocal cord leukoplakia is clinically described as a white plaque or patch on the vocal cords observed during macroscopic examination, which does not take into account histological features or prognosis. A clinical challenge in managing vocal cord leukoplakia is to assess the potential malignant transformation of the lesion. This study aims to investigate the potential of deep learning (DL) for the simultaneous segmentation and classification of vocal cord leukoplakia using narrow band imaging (NBI) and white light imaging (WLI). The primary objective is to assess the model's accuracy in detecting and classifying lesions, comparing its performance in WLI and …

Protocol For Establishing And Evaluating A Cancer Cachexia Mouse Model, Zhijun Zhou, Jingxuan Yang, Mingyang Liu, Yu Ren, Xiuhui Shi, Yang Cai, Alex X Arreola, Yi-Ping Li, Yuqing Zhang, Min Li

Faculty, Staff and Student Publications

Cancer cachexia mouse models are needed to recapitulate the clinical features of patients with cachexia. Here, we present a protocol for the establishment and evaluation of cancer cachexia mouse models. We delineate the steps in preparing tumor cells for inoculation and surgical procedures. After the establishment of these mouse models, we describe essential techniques to assess cancer cachexia, including grip strength evaluation, tissue collection, and the calculation of cross-sectional areas of muscle tissue. For complete details on the use and execution of this protocol, please refer to Liu et al.,

Survival Outcomes After Omission Of Surgery For Ductal Carcinoma In Situ, Elizabeth C Poli, Wenli Dong, Simona F Shaitelman, Nina Tamirisa, Yu Shen, Isabelle Bedrosian

Faculty, Staff and Student Publications

Clinical trials of active surveillance (AS) for Ductal Carcinoma in Situ (DCIS) are underway. We sought to understand the historical management of biologically favorable DCIS and to determine the outcomes of patients who did not have immediate surgery. Using data from the NCDB from 2004 to 2017, the selected cohort included women >40 years of age, with low or intermediate grade and hormone receptor (HR) positive DCIS. AS was defined as either no surgery or surgery >12 months from diagnosis. Women in the AS group were compared to women who had immediate surgery. A Cochran-Armitage test was used to assess …

Ablation Of The Integrin Cd11b Mac-1 Limits Deleterious Responses To Traumatic Spinal Cord Injury And Improves Functional Recovery In Mice, Yun Li, Zhuofan Lei, Rodney M Ritzel, Junyun He, Simon Liu, Li Zhang, Junfang Wu

Faculty, Staff and Student Publications

Spinal cord injury (SCI) triggers microglial/monocytes activation with distinct pro-inflammatory or inflammation-resolving phenotypes, which potentiate tissue damage or facilitate functional repair, respectively. The major integrin Mac-1 (CD11b/CD18), a heterodimer consisting of CD11b and CD18 chains, is expressed in multiple immune cells of the myeloid lineage. Here, we examined the effects of CD11b gene ablation in neuroinflammation and functional outcomes after SCI. qPCR analysis of C57BL/6 female mice showed upregulation of

Germline Mutations In A G Protein Identify Signaling Cross-Talk In T Cells, Hyoungjun Ham, Huie Jing, Ian T Lamborn, Megan M Kober, Alexey Koval, Yamina A Berchiche, D Eric Anderson, Kirk M Druey, Judith N Mandl, Bertrand Isidor, Carlos R Ferreira, Alexandra F Freeman, Sundar Ganesan, Meliha Karsak, Peter J Mustillo, Juliana Teo, Zarazuela Zolkipli-Cunningham, Nicolas Chatron, François Lecoquierre, Andrew J Oler, Jana Pachlopnik Schmid, Douglas B Kuhns, Xuehua Xu, Fabian Hauck, Waleed Al-Herz, Matias Wagner, Paulien A Terhal, Mari Muurinen, Vincent Barlogis, Phillip Cruz, Jeffrey Danielson, Helen Stewart, Petra Loid, Sebastian Rading, Boris Keren, Rolph Pfundt, Kol A Zarember, Katharina Vill, Lorraine Potocki, Kenneth N Olivier, Gaetan Lesca, Laurence Faivre, Melanie Wong, Anne Puel, Janet Chou, Maud Tusseau, Niki M Moutsopoulos, Helen F Matthews, Cas Simons, Ryan J Taft, Ariane Soldatos, Etienne Masle-Farquhar, Stefania Pittaluga, Robert Brink, Danielle L Fink, Heidi H Kong, Juraj Kabat, Woo Sung Kim, Tatjana Bierhals, Kazuyuki Meguro, Amy P Hsu, Jingwen Gu, Jennifer Stoddard, Benito Banos-Pinero, Maria Slack, Giampaolo Trivellin, Benoît Mazel, Maarja Soomann, Samuel Li, Val J Watts, Constantine A Stratakis, Maria F Rodriguez-Quevedo, Ange-Line Bruel, Marita Lipsanen-Nyman, Paul Saultier, Rashmi Jain, Daphne Lehalle, Daniel Torres, Kathleen E Sullivan, Sébastien Barbarot, Axel Neu, Yannis Duffourd, Morgan Similuk, Kirsty Mcwalter, Pierre Blanc, Stéphane Bézieau, Tian Jin, Raif S Geha, Jean-Laurent Casanova, Outi M Makitie, Christian Kubisch, Patrick Edery, John Christodoulou, Ronald N Germain, Christopher C Goodnow, Thomas P Sakmar, Daniel D Billadeau, Sébastien Küry, Vladimir L Katanaev, Yu Zhang, Michael J Lenardo, Helen C Su

Center for Medical Ethics and Health Policy Staff Publications

Humans with monogenic inborn errors responsible for extreme disease phenotypes can reveal essential physiological pathways. We investigated germline mutations in GNAI2, which encodes Gαi2, a key component in heterotrimeric G-protein signal transduction usually thought to regulate adenylyl cyclase-mediated cAMP production. Patients with activating Gαi2 mutations had clinical presentations that included impaired immunity. Mutant Gαi2 impaired cell migration and augmented responses to T cell receptor (TCR) stimulation. We found that mutant Gαi2 influenced TCR signaling by sequestering the GTPase-activating protein RASA2, thereby promoting RAS activation and increasing downstream ERK/MAPK and PI3K-AKT S6 signaling to drive cellular growth and proliferation.

Pelage Variation And Morphometrics Of Closely Related Callithrix Marmoset Species And Their Hybrids, Joanna Malukiewicz, Kerryn Warren, Vanner Boere, Illaira L C Bandeira, Nelson H A Curi, Fabio T Das Dores, Lilian S Fitorra, Haroldo R Furuya, Claudia S Igayara, Liliane Milanelo, Silvia B Moreira, Camila V Molina, Marcello S Nardi, Patricia A Nicola, Marcelo Passamani, Valeria S Pedro, Luiz C M Pereira, Bruno Petri, Alcides Pissinatti, Adriana Alves Quirino, Jeffrey Rogers, Carlos R Ruiz-Miranda, Daniel L Silva, Ita O Silva, Monique O M Silva, Juliana L Summa, Ticiana Zwarg, Rebecca R Ackermann

Faculty, Staff and Students Publications

BACKGROUND: Hybrids are expected to show greater phenotypic variation than their parental species, yet how hybrid phenotype expression varies with genetic distances in closely-related parental species remains surprisingly understudied. Here, we investigate pelage and morphometric trait variation in anthropogenic hybrids between four species of Brazilian Callithrix marmosets, a relatively recent primate radiation. Marmoset species are distinguishable by pelage phenotype and morphological specializations for eating tree exudates. In this work, we (1) describe qualitative phenotypic pelage differences between parental species and hybrids; (2) test whether significant quantitative differences exist between parental and hybrid morphometric phenotypes; and (3) determine which hybrid morphometic …

Optimization Of Cellular Transduction By The Hiv-Based Pseudovirus Platform With Pan-Coronavirus Spike Proteins, Syamala Rani Thimmiraju, Maria Jose Villar, Jason T Kimata, Ulrich Strych, Maria Elena Bottazzi, Peter J Hotez, Jeroen Pollet

Faculty, Staff and Students Publications

Over the past three years, new SARS-CoV-2 variants have continuously emerged, evolving to a point where an immune response against the original vaccine no longer provided optimal protection against these new strains. During this time, high-throughput neutralization assays based on pseudoviruses have become a valuable tool for assessing the efficacy of new vaccines, screening updated vaccine candidates against emerging variants, and testing the efficacy of new therapeutics such as monoclonal antibodies. Lentiviral vectors derived from HIV-1 are popular for developing pseudo and chimeric viruses due to their ease of use, stability, and long-term transgene expression. However, the HIV-based platform has …

Protocol For The Derivation Of Primary Cancer Stem Cell Lines From Human Ependymal Tumors, Cory M Richman, Peter B Dirks, Michael D Taylor, Kulandaimanuvel Antony Michealraj

Faculty, Staff and Students Publications

Cancer stem cells (CSCs) established from surgical biopsies closely mimic the human context and can be used to investigate disease mechanisms, genetic fitness, and therapeutic evaluation. Here, we present a protocol for the derivation of primary patient-derived CSC lines from ependymal tumors. We describe the necessary steps, from surgical intervention and biopsy to the dissociation of ependymomas to derive cultures. We then detail procedures for cell line propagation and define the characteristics of these primary cancer cell lines. For complete details on the use and execution of this protocol, please refer to Michealraj et al.

Humoral Immunity And Antibody Responses Against Diphtheria, Tetanus, And Pneumococcus After Immune Effector Cell Therapies: A Prospective Study, Georgios Angelidakis, Roy F Chemaly, Pranoti V Sahasrabhojane, Oscar Morado-Aramburo, Ying Jiang, Micah M Bhatti, Elizabeth Shpall, Chitra Hosing, Preetesh Jain, Kris Michael Mahadeo, Fareed Khawaja, Peter Elhajj, Jennifer A Wargo, Robert R Jenq, Nadim J Ajami, Partow Kebriaei, Ella J Ariza-Heredia

Faculty, Staff and Student Publications

Patients undergoing immune effector cell therapy (IECT) are at high risk for infections. We assessed seropositivity against pneumococcus, tetanus, and diphtheria in patients before and after IECT and the patients' response to vaccination. We enrolled patients who underwent IECT from January 2020 to March 2022. Antibody levels for diphtheria, tetanus, and pneumococcus were measured before IECT, at 1 month, and 3-6 months after. Eligible patients were vaccinated after IECT. In non-seroprotected patients, we discontinued testing. Before IECT, most patients had seroprotective antibody levels against tetanus (68/69, 99%) and diphtheria (65/69, 94%), but fewer did against pneumococcus (24/67, 36%). After IECT, …

Production Of Genetically Stable And Odontoglossum Ringspot Virus-Free Cymbidium Orchid ‘New True’ Plants Via Meristem-Derived Protocorm-Like Body (Plb) Subcultures, Jova Riza Campol, Aung Htay Naing, Hay Mon Aung, Su Bin Cho, Hyunhee Kang, Mi Young Chung, Chang Kil Kim

Faculty, Staff and Student Publications

BACKGROUND: This study aimed to produce Odontoglossum ringspot virus (ORSV)-free Cymbidium orchid 'New True' plants from ORSV-infected mother plants by culturing their meristems and successively repeating subcultures of protocorm-like bodies (PLBs) derived from the meristems.

RESULTS: Initially, ORSV was confirmed as the causative agent of viral symptoms in orchid leaves via reverse transcription-polymerase chain reaction (RT-PCR) analysis. Meristems from infected plants were cultured to generate PLBs, which in sequence were repeatedly subcultured up to four times. RT-PCR and quantitative RT-PCR analyses revealed that while ORSV was undetectable in shoots derived from the first subculture, complete elimination of the virus required …

Sequence-To-Expression Approach To Identify Etiological Non-Coding Dna Variations In P53 And Cmyc-Driven Diseases, Katherine Kin, Shounak Bhogale, Lisha Zhu, Derrick Thomas, Jessica Bertol, W Jim Zheng, Saurabh Sinha, Walid D Fakhouri

Faculty, Staff and Student Publications

Disease risk prediction based on genomic sequence and transcriptional profile can improve disease screening and prevention. Despite identifying many disease-associated DNA variants, distinguishing deleterious non-coding DNA variations remains poor for most common diseases. In this study, we designed in vitro experiments to uncover the significance of occupancy and competitive binding between P53 and cMYC on common target genes. Analyzing publicly available ChIP-seq data for P53 and cMYC in embryonic stem cells showed that ~344-366 regions are co-occupied, and on average, two cis-overlapping motifs (CisOMs) per region were identified, suggesting that co-occupancy is evolutionarily conserved. Using U2OS and Raji cells untreated …

Current Status And Research Directions In Acute Myeloid Leukemia, Hagop Kantarjian, Gautam Borthakur, Naval Daver, Courtney D Dinardo, Ghayas Issa, Elias Jabbour, Tapan Kadia, Koji Sasaki, Nicholas J Short, Musa Yilmaz, Farhad Ravandi

Faculty, Staff and Student Publications

The understanding of the molecular pathobiology of acute myeloid leukemia (AML) has spurred the identification of therapeutic targets and the development of corresponding novel targeted therapies. Since 2017, twelve agents have been approved for the treatment of AML subsets: the BCL2 inhibitor venetoclax; the CD33 antibody drug conjugate gemtuzumab ozogamicin; three FLT3 inhibitors (midostaurin, gilteritinib, quizartinib); three IDH inhibitors (ivosidenib and olutasidenib targeting IDH1 mutations; enasidenib targeting IDH2 mutations); two oral hypomethylating agents (oral poorly absorbable azacitidine; fully absorbable decitabine-cedazuridine [latter approved as an alternative to parenteral hypomethylating agents in myelodysplastic syndrome and chronic myelomonocytic leukemia but commonly used in …

The P-Myh9/Usp22/Hif-1Α Axis Promotes Lenvatinib Resistance And Cancer Stemness In Hepatocellular Carcinoma, Qiaonan Shan, Lu Yin, Qifan Zhan, Jiongjie Yu, Sheng Pan, Jianyong Zhuo, Wei Zhou, Jiaqi Bao, Lincheng Zhang, Jiachen Hong, Jianan Xiang, Qingyang Que, Kangchen Chen, Shengjun Xu, Jingrui Wang, Yangbo Zhu, Bin He, Jingbang Wu, Haiyang Xie, Shusen Zheng, Tingting Feng, Sunbin Ling, Xiao Xu

Faculty, Staff and Student Publications

Lenvatinib is a targeted drug used for first-line treatment of hepatocellular carcinoma (HCC). A deeper insight into the resistance mechanism of HCC against lenvatinib is urgently needed. In this study, we aimed to dissect the underlying mechanism of lenvatinib resistance (LR) and provide effective treatment strategies. We established an HCC model of acquired LR. Cell counting, migration, self-renewal ability, chemoresistance and expression of stemness genes were used to detect the stemness of HCC cells. Molecular and biochemical strategies such as RNA-sequencing, immunoprecipitation, mass spectrometry and ubiquitination assays were used to explore the underlying mechanisms. Patient-derived HCC models and HCC samples …

Diagnostic Error In Mental Health: A Review, Andrea Bradford, Ashley N D Meyer, Sundas Khan, Traber D Giardina, Hardeep Singh

Faculty, Staff and Students Publications

Diagnostic errors are associated with patient harm and suboptimal outcomes. Despite national scientific efforts to advance definition, measurement and interventions for diagnostic error, diagnosis in mental health is not well represented in this ongoing work. We aimed to summarise the current state of research on diagnostic errors in mental health and identify opportunities to align future research with the emerging science of diagnostic safety. We review conceptual considerations for defining and measuring diagnostic error, the application of these concepts to mental health settings, and the methods and subject matter focus of recent studies of diagnostic error in mental health. We …

Exploring The Complexity Of Systemic Sclerosis Etiology By Trio Whole Genome Sequencing, Hongzheng Dai, Shamika Ketkar, Taotao Tan, Elizabeth G Atkinson, Lindsay Burrage, Kim C Worley, Brian Christopher, Marka A Lyons, Shervin Assassi, Maureen D Mayes, Brendan Lee

Faculty, Staff and Students Publications

Systemic sclerosis (SSc) is a heterogeneous rare autoimmune fibrosing disorder affecting connective tissue. The etiology of systemic sclerosis is largely unknown and many genes have been suggested as susceptibility loci of modest impact by genome-wide association study (GWAS). Multiple factors can contribute to the pathological process of the disease, which makes it more difficult to identify possible disease-causing genetic alterations. In this study, we have applied whole genome sequencing (WGS) in 101 indexed family trios, supplemented with transcriptome sequencing on cultured fibroblast cells of four patients and five family controls where available. Single nucleotide variants (SNVs) and copy number variants …

Frequent Chd1 Deletions In Prostate Cancers Of African American Men Is Associated With Rapid Disease Progression, Miklos Diossy, Viktoria Tisza, Hua Li, Pranshu Sahgal, Jia Zhou, Zsofia Sztupinszki, Denise Young, Darryl Nousome, Claire Kuo, Jiji Jiang, Yongmei Chen, Reinhard Ebner, Isabell A Sesterhenn, Joel T Moncur, Gregory T Chesnut, Gyorgy Petrovics, Gregory T Klus, Gabor Valcz, Pier Vitale Nuzzo, Dezso Ribli, Judit Börcsök, Aurel Prosz, Marcin Krzystanek, Thomas Ried, David Szuts, Kinza Rizwan, Salma Kaochar, Shailja Pathania, Alan D D'Andrea, Istvan Csabai, Shiv Srivastava, Matthew L Freedman, Albert Dobi, Sandor Spisak, Zoltan Szallasi

Faculty, Staff and Students Publications

We analyzed genomic data from the prostate cancer of African- and European American men to identify differences contributing to racial disparity of outcome. We also performed FISH-based studies of Chromodomain helicase DNA-binding protein 1 (CHD1) loss on prostate cancer tissue microarrays. We created CHD1-deficient prostate cancer cell lines for genomic, drug sensitivity and functional homologous recombination (HR) activity analysis. Subclonal deletion of CHD1 was nearly three times as frequent in prostate tumors of African American than in European American men and it associates with rapid disease progression. CHD1 deletion was not associated with HR deficiency associated mutational signatures or HR …

Target Heart Rate Formulas For Exercise Stress Testing: What Is The Evidence?, Omar Almaadawy, Barry F Uretsky, Chayakrit Krittanawong, Yochai Birnbaum

Faculty, Staff and Students Publications

Exercise stress testing (EST) is commonly used to evaluate chest pain, with some labs using 85% of age-predicted maximum heart rate (APMHR) as an endpoint for EST. The APMHR is often calculated using the formula 220-age. However, the accuracy of this formula and 85% APMHR as an endpoint may be questioned. Moreover, failing to reach 85% APMHR (known as chronotropic insufficiency) may also indicate poor cardiovascular prognosis, but measurements, such as percentage heart rate reserve (%HRR), maximum rate pressure product (MRPP), and the maximum metabolic equivalent of tasks (METs) reached during EST may provide better prediction of cardiovascular outcomes than …

Rethinking Health Systems Responsiveness In Low- And Middle-Income Countries: Validation Study, Meesha Iqbal, Cecilia Ganduglia Cazaban, Robert Morgan, Cici Bauer, Sameen Siddiqi

Faculty, Staff and Student Publications

BACKGROUND: Health systems responsiveness (HSR) is the ability of systems to respond to legitimate non-health expectations of the population. The concept of HSR by the World Health Organization (WHO) includes respect for dignity, individual autonomy, confidentiality, prompt attention to care, availability of basic amenities, choice of provider, access to social support networks, and clarity of communication. The WHO tool is applied globally to assess HSR in low, middle, and high-income countries.

OBJECTIVE: We have revised the conceptual framework of HSR following a rigorous systematic review and made it specific for low- and middle-income countries (L&MICs). This study is designed to …

Loss Of P53 And Smad4 Induces Adenosquamous Subtype Pancreatic Cancer In The Absence Of An Oncogenic Kras Mutation, Daowei Yang, Xinlei Sun, Rohan Moniruzzaman, Hua Wang, Citu Citu, Zhongming Zhao, Ignacio I Wistuba, Huamin Wang, Anirban Maitra, Yang Chen

Faculty, Staff and Student Publications

Pancreatic cancer is associated with an oncogenic KRAS mutation in approximately 90% of cases. However, a non-negligible proportion of pancreatic cancer cases harbor wild-type KRAS (KRAS-WT). This study establishes genetically engineered mouse models that develop spontaneous pancreatic cancer in the context of KRAS-WT. The Trp53

Association Between Non-Injection Drug Use And Hepatitis C Infection Among Hiv-Negative Men Who Have Sex With Men, Jing Zhao, Charles Green, Christine Markham, Kayo Fujimoto, Alan G Nyitray, Lu-Yu Hwang

Faculty, Staff and Student Publications

Background: Prior research predominantly examined the association between HIV-positive men who have sex with men (MSM) or those using injection drugs and hepatitis C virus (HCV) infection. However, limited attention has been given to understanding the association among HIV-negative MSM who do not inject drugs. This gap leaves apportion of the population unexamined, potentially overlooking important factor that may contribute to the transmission and prevalence of HCV. This study aims to investigate the relationship between non-injection drug use and HCV infection in this population.

Methods: In this cross-sectional study, we analyzed data on 118 MSM who reported use of non-injection …

Effects Of Sotagliflozin On Health Status In Patients With Worsening Heart Failure: Results From Soloist-Whf, Ankeet S Bhatt, Deepak L Bhatt, Ph Gabriel Steg, Michael Szarek, Christopher P Cannon, Lawrence A Leiter, Darren K Mcguire, Julia B Lewis, Matthew C Riddle, Adriaan A Voors, Marco Metra, Lars H Lund, Jeffrey M Testani, Christopher S Wilcox, Michael Davies, Bertram Pitt, Mikhail N Kosiborod

Faculty, Staff and Student Publications

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve health status in heart failure (HF) across the left ejection fraction ejection spectrum. However, the effects of SGLT1 and SGLT2 inhibition on health status are unknown.

Objectives: These prespecified analyses of the SOLOIST-WHF (Effect of Sotagliflozin on Cardiovascular Events in Patients with Type 2 Diabetes Post Worsening Heart Failure) trial examined the effects of sotagliflozin vs placebo on HF-related health status.

Methods: SOLOIST-WHF randomized patients hospitalized or recently discharged after a worsening HF episode to receive sotagliflozin or placebo. The primary endpoint was total number of HF hospitalizations, urgent HF visits, and cardiovascular …

Perfusion-Weighted Imaging With Dynamic Contrast Enhancement (Pwi/Dce) Morphologic, Qualitative, Semiquantitative, And Radiomics Features Predicting Undifferentiated Pleomorphic Sarcoma (Ups) Treatment Response, R F Valenzuela, E Duran-Sierra, M Canjirathinkal, B Amini, K E Torres, R S Benjamin, J Ma, W L Wang, K P Hwang, R J Stafford, C Wu, A M Zarzour, A J Bishop, S Lo, J E Madewell, R Kumar, W A Murphy, C M Costelloe

Faculty, Staff and Student Publications

Undifferentiated pleomorphic sarcoma (UPS) is the largest subgroup of soft tissue sarcomas. This study determined the value of perfusion-weighted imaging with dynamic-contrast-enhancement (PWI/DCE) morphologic, qualitative, and semiquantitative features for predicting UPS pathology-assessed treatment effect (PATE). This retrospective study included 33 surgically excised extremity UPS patients with pre-surgical MRI. Volumetric tumor segmentation from PWI/DCE was obtained at Baseline (BL), Post-Chemotherapy (PC), and Post-Radiation Therapy (PRT). The surgical specimens' PATE separated cases into Responders (R) (≥ 90%, 16 patients), Partial-Responders (PR) (89 - 31%, 10 patients), and Non-Responders (NR) (≤ 30%, seven patients). Seven semiquantitative kinetic parameters and maps were extracted from …

Detecting Altered Hepatic Lipid Oxidation By Mri In An Animal Model Of Masld, Marc Mcleod, Mario C Chang, Anna Rushin, Mukundan Ragavan, Rohit Mahar, Gaurav Sharma, Arshee Badar, Anthony Giacalone, Max E Glanz, Vinay R Malut, Dalton Graham, Nishanth E Sunny, James A Bankson, Kenneth Cusi, Matthew E Merritt

Faculty, Staff and Student Publications

Metabolic dysfunction-associated steatotic liver disease (MASLD) prevalence is increasing annually and affects over a third of US adults. MASLD can progress to metabolic dysfunction-associated steatohepatitis (MASH), characterized by severe hepatocyte injury, inflammation, and eventual advanced fibrosis or cirrhosis. MASH is predicted to become the primary cause of liver transplant by 2030. Although the etiology of MASLD/MASH is incompletely understood, dysregulated fatty acid oxidation is implicated in disease pathogenesis. Here, we develop a method for estimating hepatic β-oxidation from the metabolism of [D