Medicine and Health Sciences Commons^™

Predictors Of Transition From Child And Adolescent Bipolar Not Otherwise Specified To Bipolar I Disorder, A Longitudinal 3.9-Year Study., María Ribeiro-Fernández, Azucena Díez-Suárez, Kiki D Chang, Cesar A Soutullo

Faculty, Staff and Student Publications

Background: Children and adolescents with subthreshold manic symptoms not meeting full DSM criteria for bipolar I or II disorder (BP-I or BP-II) are classified as unspecified bipolar disorder (formerly bipolar not otherwise specified: BP-NOS). Factors associated with transition from BP-II or NOS to BP-I may predict the progression of the disorder. Our objective is to analyze factors associated with transition to BP-I in a Spanish sample of youth with BP-NOS or BP-II.

Methods: We included all youth diagnosed with BP before 18 years of age presenting to our clinic (October 1999-December 2014). We assessed clinical factors that may predict transition …

Stimulation Of An Entorhinal-Hippocampal Extinction Circuit Facilitates Fear Extinction In A Post-Traumatic Stress Disorder Model, Ze-Jie Lin, Xue Gu, Wan-Kun Gong, Mo Wang, Yan-Jiao Wu, Qi Wang, Xin-Rong Wu, Xin-Yu Zhao, Michael X Zhu, Lu-Yang Wang, Quanying Liu, Ti-Fei Yuan, Wei-Guang Li, Tian-Le Xu

Faculty, Staff and Student Publications

Effective psychotherapy of post-traumatic stress disorder (PTSD) remains challenging owing to the fragile nature of fear extinction, for which the ventral hippocampal CA1 (vCA1) region is considered as a central hub. However, neither the core pathway nor the cellular mechanisms involved in implementing extinction are known. Here, we unveil a direct pathway, where layer 2a fan cells in the lateral entorhinal cortex (LEC) target parvalbumin-expressing interneurons (PV-INs) in the vCA1 region to propel low-gamma-band synchronization of the LEC-vCA1 activity during extinction learning. Bidirectional manipulations of either hippocampal PV-INs or LEC fan cells sufficed for fear extinction. Gamma entrainment of vCA1 …

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 …

Thrombectomy For Stroke With Large Infarct On Noncontrast Ct: The Tesla Randomized Clinical Trial, Writing Committee For The Tesla Investigators, Albert J Yoo, Osama O Zaidat, Sunil A Sheth, Ansaar T Rai, Santiago Ortega-Gutierrez, Curtis A Given, Syed F Zaidi, Ramesh Grandhi, Hugo Cuellar, Maxim Mokin, Jeffrey M Katz, Amer Alshekhlee, Muhammad A Taqi, Sameer A Ansari, Adnan H Siddiqui, Nobl Barazangi, Joey D English, Alberto Maud, Jawad Kirmani, Rishi Gupta, Dileep R Yavagal, Jason Tarpley, Dhruvil J Pandya, Marshall C Cress, Sushrut Dharmadhikari, Kaiz S Asif, Tareq Kass-Hout, Ajit S Puri, Nazli Janjua, Aniel Q Majjhoo, Aamir Badruddin, Randall C Edgell, Rakesh Khatri, Larry Morgan, Anmar Razak, Alicia Zha, Priyank Khandelwal, Nils Mueller-Kronast, Dennis J Rivet, Thomas Wolfe, Brian Snelling, Ali Sultan-Qurraie, Shao-Pow Lin, Rajkamal Khangura, Alejandro M Spiotta, Parita Bhuva, Sergio Salazar-Marioni, Eugene Lin, Abdul R Tarabishy, Edgar A Samaniego, Murali K Kolikonda, Mouhammad A Jumaa, Vivek K Reddy, Pankaj Sharma, Olvert A Berkhemer, Pieter-Jan Van Doormaal, Adriaan C G M Van Es, Wim H Van Zwam, Bart J Emmer, Ludo F Beenen, Charles B L M Majoie, Nancy Buderer, Michelle A Detry, Anna Bosse, Todd L Graves, Christina Saunders, Lucas Elijovich, Ashutosh Jadhav, Mary Patterson, Hannah Slight, Kristine Below, Sami Al Kasab, Tesla Investigators

Faculty, Staff and Student Publications

Importance: Recent large infarct thrombectomy trials used heterogeneous imaging modalities and time windows for patient selection. Noncontrast computed tomographic (CT) scan is the most common stroke imaging approach. It remains uncertain whether thrombectomy is effective for patients with large infarcts identified using noncontrast CT alone within 24 hours of stroke onset.

Objective: To evaluate the effect of thrombectomy in patients with a large infarct on a noncontrast CT scan within 24 hours of onset.

Design, setting, and participants: Open-label, blinded-end point, bayesian-adaptive randomized trial with interim analyses for early stopping (futility or success) or population enrichment, which was conducted at …

Metadegron: Multimodal Feature-Integrated Protein Language Model For Predicting E3 Ligase Targeted Degrons, Mengqiu Zheng, Shaofeng Lin, Kunqi Chen, Ruifeng Hu, Liming Wang, Zhongming Zhao, Haodong Xu

Faculty, Staff and Student Publications

Protein degradation through the ubiquitin proteasome system at the spatial and temporal regulation is essential for many cellular processes. E3 ligases and degradation signals (degrons), the sequences they recognize in the target proteins, are key parts of the ubiquitin-mediated proteolysis, and their interactions determine the degradation specificity and maintain cellular homeostasis. To date, only a limited number of targeted degron instances have been identified, and their properties are not yet fully characterized. To tackle on this challenge, here we develop a novel deep-learning framework, namely MetaDegron, for predicting E3 ligase targeted degron by integrating the protein language model and comprehensive …

Mta-Cooperative Prmt5 Inhibitors Enhance T Cell-Mediated Antitumor Activity In Mtap-Loss Tumors, Si Chen, Jiakai Hou, Roshni Jaffery, Ashley Guerrero, Rongjie Fu, Leilei Shi, Ningbo Zheng, Ritu Bohat, Nicholas A Egan, Chengtai Yu, Sana Sharif, Yue Lu, Wei He, Shuyue Wang, Donjeta Gjuka, Everett M Stone, Pooja Anil Shah, Jordi Rodon Ahnert, Taiping Chen, Xinli Liu, Mark T Bedford, Han Xu, Weiyi Peng

Faculty, Staff and Student Publications

BACKGROUND: Hyperactivated protein arginine methyltransferases (PRMTs) are implicated in human cancers. Inhibiting tumor intrinsic PRMT5 was reported to potentiate antitumor immune responses, highlighting the possibility of combining PRMT5 inhibitors (PRMT5i) with cancer immunotherapy. However, global suppression of PRMT5 activity impairs the effector functions of immune cells. Here, we sought to identify strategies to specifically inhibit PRMT5 activity in tumor tissues and develop effective PRMT5i-based immuno-oncology (IO) combinations for cancer treatment, particularly for methylthioadenosine phosphorylase (MTAP)-loss cancer.

METHODS: Isogeneic tumor lines with and without MTAP loss were generated by CRISPR/Cas9 knockout. The effects of two PRMT5 inhibitors (GSK3326595 and MRTX1719) were …

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 …

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

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 …

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 …

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 …

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

Gut Phageome In Mexican Americans: A Population At High Risk For Metabolic Dysfunction-Associated Steatotic Liver Disease And Diabetes, Suet-Ying Kwan, Caroline M Sabotta, Lorenzo R Cruz, Matthew C Wong, Nadim J Ajami, Joseph B Mccormick, Susan P Fisher-Hoch, Laura Beretta

Faculty, Staff and Student Publications

Mexican Americans are disproportionally affected by metabolic dysfunction-associated steatotic liver disease (MASLD), which often co-occurs with diabetes. Despite extensive evidence on the causative role of the gut microbiome in MASLD, studies determining the involvement of the gut phageome are scarce. In this cross-sectional study, we characterized the gut phageome in Mexican Americans of South Texas by stool shotgun metagenomic sequencing of 340 subjects, concurrently screened for liver steatosis by transient elastography. Inter-individual variations in the phageome were associated with gender, country of birth, diabetes, and liver steatosis. The phage signatures for diabetes and liver steatosis were subsequently determined. Enrichment of …

Loss Of Hd-Ptp Function Results In Lipodystrophy, Defective Cellular Signaling And Altered Lipid Homeostasis, Destiny F Schultz, Brian A Davies, Johanna A Payne, Cole P Martin, Annabel Y Minard, Bennett G Childs, Cheng Zhang, Karthik B Jeganathan, Ines Sturmlechner, Thomas A White, Alain De Bruin, Liesbeth Harkema, Huiqin Chen, Michael A Davies, Sarah Jachim, Nathan K Lebrasseur, Robert C Piper, Hu Li, Darren J Baker, Jan Van Deursen, Daniel D Billadeau, David J Katzmann

Faculty, Staff and Student Publications

His domain protein tyrosine phosphatase (HD-PTP; also known as PTPN23) facilitates function of the endosomal sorting complexes required for transport (ESCRTs) during multivesicular body (MVB) formation. To uncover its role in physiological homeostasis, embryonic lethality caused by a complete lack of HD-PTP was bypassed through generation of hypomorphic mice expressing reduced protein, resulting in animals that are viable into adulthood. These mice exhibited marked lipodystrophy and decreased receptor-mediated signaling within white adipose tissue (WAT), involving multiple prominent pathways including RAS/MAPK, phosphoinositide 3-kinase (PI3K)/AKT and receptor tyrosine kinases (RTKs), such as EGFR. EGFR signaling was dissected in vitro to assess the …

Longitudinal Intravascular Antibody Labeling Identified Regulatory T Cell Recruitment As A Therapeutic Target In A Mouse Model Of Lung Cancer, Sean-Luc Shanahan, Nikesh Kunder, Charles Inaku, Natalie B Hagan, Grace Gibbons, Nicolas Mathey-Andrews, Gayathri Anandappa, Shawn Soares, Kristen E Pauken, Tyler Jacks, Jason M Schenkel

Faculty, Staff and Student Publications

Anticancer immunity is predicated on leukocyte migration into tumors. Once recruited, leukocytes undergo substantial reprogramming to adapt to the tumor microenvironment. A major challenge in the field is distinguishing recently recruited from resident leukocytes in tumors. In this study, we developed an intravascular Ab technique to label circulating mouse leukocytes before they migrate to tissues, providing unprecedented insight into the kinetics of recruitment. This approach unveiled the substantial role of leukocyte migration in tumor progression using a preclinical mouse model of lung adenocarcinoma. Regulatory T cells (Tregs), critical mediators of immunosuppression, were continuously and rapidly recruited into tumors throughout cancer …

Hif-2Α-Dependent Induction Of Mir-29a Restrains Th1 Activity During T Cell Dependent Colitis, Agnieszka K Czopik, Eóin N Mcnamee, Victoria Vaughn, Xiangsheng Huang, In Hyuk Bang, Trent Clark, Yanyu Wang, Wei Ruan, Tom Nguyen, Joanne C Masterson, Eunyoung Tak, Sandra Frank, Colm B Collins, Howard Li, Cristian Rodriguez-Aguayo, Gabriel Lopez-Berestein, Mark E Gerich, Glenn T Furuta, Xiaoyi Yuan, Anil K Sood, Edwin F De Zoeten, Holger K Eltzschig

Faculty, Staff and Student Publications

Metabolic imbalance leading to inflammatory hypoxia and stabilization of hypoxia-inducible transcription factors (HIFs) is a hallmark of inflammatory bowel diseases. We hypothesize that HIF could be stabilized in CD4+ T cells during intestinal inflammation and alter the functional responses of T cells via regulation of microRNAs. Our assays reveal markedly increased T cell-intrinsic hypoxia and stabilization of HIF protein during experimental colitis. microRNA screen in primary CD4+ T cells points us towards miR-29a and our subsequent studies identify a selective role for HIF-2α in CD4-cell-intrinsic induction of miR-29a during hypoxia. Mice with T cell-intrinsic HIF-2α deletion display elevated T-bet (target …

A Qualitative Study Of The Knowledge Of Metabolic Syndrome, Attitudes About Lifestyle Modifications, And Preferences For Lifestyle Interventions Among Patients With Cancer And Metabolic Syndrome, Isabel Martinez Leal, Ashwathy B Pillai, Jessica T Foreman, Kimberly W Siu, Natalia I Heredia, Carmen P Escalante, Ellen F Manzullo, Aimee J Christie, Tamara E Lacourt, Zayd Adnan Razouki, Jessica P Hwang

Faculty, Staff and Student Publications

Metabolic syndrome is a group of disorders-hypertension, dyslipidemia, obesity, and insulin resistance-that together increase the risk of coronary heart disease, stroke, and diabetes. Although ~60% of cancer patients have metabolic syndrome, which increases their risk of mortality, oncology providers lack clear guidance about its management. The development of metabolic syndrome lifestyle interventions requires a better understanding of these patients' knowledge, attitudes, and intervention preferences in order to inform management. During 2022-2023, 19 adult cancer patients with metabolic syndrome engaged in semistructured interviews focused on metabolic syndrome and lifestyle interventions. Interviews were analyzed using hybrid thematic analysis involving deductive and inductive …