Medical Specialties Commons^™

Prevalence Of Her2-Low Status And Outcomes In Early-Stage Her2-Negative Breast Cancer, Akshara Singareeka Raghavendra, Diane D Liu, Sarah Pasyar, Senthil Damodaran, Yu Shen, Carlos H Barcenas

Faculty, Staff and Student Publications

HER2-low breast cancer (IHC 1+ or 2+ without HER2 gene amplification) is a distinct and understudied subtype. In a cohort of 14,593 early-stage breast cancer patients treated at MD Anderson from 2006 to 2019, 60.4% were HER2-low. Multivariable analysis showed HER2-low status was independently associated with race, histologic subtype, higher nuclear grade and stage, and estrogen receptor (ER) positivity. Among 2464 patients receiving neoadjuvant chemotherapy, HER2-low status was not linked to pathologic complete response (pCR), overall survival (OS), or disease-free survival (DFS) compared to HER2-0 tumors. Factors predicting pCR included nuclear grade III, stage I, invasive ductal carcinoma, lower ER/PR …

Multimodal Spatial-Omics Reveal Co-Evolution Of Alveolar Progenitors And Proinflammatory Niches In Progression Of Lung Precursor Lesions, Fuduan Peng, Ansam Sinjab, Yibo Dai, Warapen Treekitkarnmongkol, Sujuan Yang, Lorena I Gomez Bolanos, Tieling Zhou, Minyue Chen, Alejandra G Serrano, Avantika Krishna, Nastaran Karimi, Manvi Sharma, Akshay Basi, Guangsheng Pei, Jianlong Liao, Yunhe Liu, Jiping Feng, Zahraa Rahal, Yang Liu, Jiahui Jiang, Kai Yu, Tala Noun, Yuejiang Liu, Khaja Khan, Kyung Serk Cho, Jichao Chen, Luisa M Solis, Sarah Mazzilli, Steven Dubinett, Tina Cascone, Avrum E Spira, Stephen Swisher, Naoe Jimbo, Takuo Hayashi, Satsuki Kishikawa, Kazuya Takamochi, Tomoo Itoh, Takashi Yao, Kenji Suzuki, Neda Kalhor, Ignacio I Wistuba, Mingyao Li, Seyed Javad Moghaddam, Junya Fujimoto, Jared Burks, Jeffrey Myers, Kadir Akdemir, Linghua Wang, Humam Kadara

Faculty, Staff and Student Publications

The co-evolution of different cell subsets in the progression of precursor lesions to lung adenocarcinoma (LUAD) is incompletely understood. We generated spatial transcriptomic maps of 56 human precursor lesions and LUADs from 25 patients and of an independent cohort of 36 lesions from 19 patients, analyzing a total of 486,519 spots and 5.4 million cells. We identify region-specific programs that distinguish precursors from LUADs. Spatially resolved clonal architectures reveal patient-specific heterogeneity in evolution of precursors to LUADs. We find epithelial alveolar progenitors expressing tumor-associated meta-programs and residing in niches enriched with proinflammatory subsets including IL1B high macrophages. Epithelial-proinflammatory niches are …

Myokine Sirpα Exacerbates Kidney Disease In Diabetes, Qingtian Li, Helena Zhang, Bhuvaneswari Krishnan, David Sheikh-Hamad, Zhaoyong Hu, William E Mitch, Sandhya S Thomas

Faculty, Staff and Students Publications

Mechanisms responsible for skeletal muscle kidney crosstalk have not been defined. We have determined that a circulating mediator, signal regulatory protein α (SIRPα), impairs intracellular insulin-mediated functions. To elucidate the effect of myokine SIRPα on diabetic kidney disease (DKD), flox mice and muscle-specific (m-specific) SIRPα-KO mice were subjected to an obesity-induced model of diabetes, high-fat diet (HFD; 60%) or insulin-deficient hyperglycemia model, streptozotocin (STZ), and were subsequently exposed to anti-SIRPα monoclonal antibodies. In the obesity-induced diabetic mice, serum SIRPα increased. Genetic deletion of muscle SIRPα protected against obesity and improved intracellular insulin signaling in muscle and adipose tissue, with reduced …

“U’R-In(E)!- Urine-Albumin-Creatinine Ratio–The Old Kid On A New Block!

Faculty, Staff and Students Publications

No abstract provided.

Discovery And Characterization Of A Novel Pseudomonas Phage Of A New Genus

Faculty, Staff and Students Publications

Background: Bacteriophages exhibit great diversity and are classically divided into lytic and temperate lifestyles. Commonly, bioinformatics is used to predict the temperate lifestyle. As the nosocomial pathogen Pseudomonas aeruginosa is common in freshwater, this biome represents an ideal location for the discovery of Pseudomonas phages.

Materials and methods: We characterized a genetically distinct species of Pseudomonas phage using next-generation sequencing and conventional microbiological methods. We characterized its lifestyle by purifying infected colonies and identifying persistent phage production.

Results: Genetics revealed a phage of a novel genus. Characterization showed a narrow host range and bioinformatics suggested a lytic lifestyle. Experimental data …

Impaired Arginine, Citrulline And Glutamine Metabolism In Type 2 Diabetes: Insights From A Stable Isotope Study, Mustafa Tosur, Raven A Wierzchowska-Mcnew, Nicolaas E P Deutz, Mariëlle P K J Engelen

Children’s Nutrition Research Center Staff Publications

Context: Arginine (Arg) is an important amino acid in T2D as a potent insulin secretagogue and precursor for nitric oxide (NO). Citrulline (Cit), the substrate for de novo Arg synthesis, is mostly produced from glutamine (Gln).

Objective: We aimed to investigate their metabolism in T2D using novel stable isotope tracer approach.

Methods: We studied 42 individuals (21 with T2D, 21 controls). After overnight fasting, blood samples were collected following pulse administration of stable amino acid tracers. Plasma concentrations and isotopic enrichments were measured by LC-MS/MS, and compartmental analyses were performed to calculate their whole-body production (WBP) rates and kinetics.

Results: …

Artificial Intelligence In Medical Ethics Education: A Descriptive Study Of Eight Models In Multiple Choice Question Generation, John Obeid, Christopher Bobier, Alex Gillham, Adam Omelianchuk, Daniel Hurst

Center for Medical Ethics and Health Policy Staff Publications

Introduction: Integrating artificial intelligence (AI) into medical education poses barriers and opportunities for medical educators. One of those opportunities is content creation for medical ethics assessment. Assessing the performance of AI in generating multiple choice questions (MCQs) in ethics that aligns with United States Medical Licensing Examination (USMLE) is important. The present study evaluates the performance of eight AI models-GPT-4 Turbo, GPT-3.5 Turbo 0125, o1 Mini, o1 Preview, GPT-4, Claude 3.5 Sonnet, Claude 3 Opus, and Gemini-in regard to the relevance, clarity, and accuracy of generated ethics-based MCQs.

Methods: Each of the eight models was tasked with generating two sets …

Shoulder Strength And Total Arc Range Of Motion: Associations With Upper-Extremity Joint Kinetics And Ball Velocity In Adolescent Baseball Pitchers, Tomohiro Ide, Stephen J. Thomas, Takato Ogasawara, Adam B. Rosen, Brian A. Knarr, Kazuma Akehi, Samuel J. Wilkins

Department of Exercise Science Faculty Papers

BACKGROUND: Adolescent baseball pitchers are vulnerable to upper-extremity injuries because of the repetitive, high-stress nature of throwing movements. While shoulder strength and range of motion (ROM) are commonly measured, they are often interpreted in isolation during injury prevention assessments.

PURPOSE: To determine the relationship between clinical measures (shoulder ROM and strength) and throwing arm joint kinetics in adolescent baseball pitchers.

STUDY DESIGN: Descriptive laboratory study.

METHODS: This study was conducted in a laboratory setting. A total of 43 adolescent baseball pitchers (age, 15-18 years) were recruited through convenience sampling. Participants underwent clinical assessments of shoulder ROM and isokinetic concentric strength …

Human Papillomavirus Vaccine Perceptions Among Noncollege Young Adults And Tiktok Influencers: Qualitative Study, Amelia Burke-Garcia, Dasha Afanaseva, Erin Cutroneo, Kayla Madden, Angela Sustaita-Ruiz, Estefany Rivera Sanchez, Amy Leader

Department of Medical Oncology Faculty Papers

BACKGROUND: Human papillomavirus (HPV) vaccination is a proven and effective tool for preventing several types of cancers, yet vaccination rates among young adults remain suboptimal, particularly among those not enrolled in 4-year colleges. This population can be more difficult to reach due to fewer established institutional touchpoints, limited engagement with campus-based health services, and greater variability in access to preventive care. At the same time, social media has become a dominant source of information for young adults, with TikTok (ByteDance) emerging as one of the most widely used platforms. Approximately 41% of TikTok's users are between the ages of 16 …

Dupilumab Beyond The Airway: Decreased Morbidity In A Real-World Analysis, Emma J. Anisman, Spencer Short, Emma Tam, Benjamin F. Bitner, Abdulghafoor Alani, Marc Rosen, Mindy Rabinowitz, Damaris Pena Evertz, Elina Toskala, Gurston G. Nyquist

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Background: Post hoc analyses of clinical trials have characterized dupilumab's adverse effects, yet the real-world impact in chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma is not well described. This study aims to characterize the risks of lymphoma, cardiovascular events, eosinophilia, joint pain, inflammatory arthritis, and sleep apnea in dupilumab-treated CRSwNP and/or asthma patients compared to those not taking dupilumab, and to other biologics.

Methods: This retrospective cohort study used TriNetX, a de-identified database containing over 100 million patient records. Demographics and adverse effects associated with immunotherapy use were collected.

Results: We identified 21,249 dupilumab-treated CRSwNP and/or asthma patients. After …

Tracking Focal Adhesion Turnover: A Novel Reporter For Fa-Phagy Flux, Kuizhi Qu, Mengjun Dai, Ying Jiang, Sophie Liu, John P Hagan, Zhen Xu

Faculty, Staff and Student Publications

Focal adhesions (FAs) are critical multi-protein complexes regulating cell adhesion, migration, and survival, and their dysregulation contributes to cancer metastasis and vascular diseases. Despite extensive research on FA formation, little is known about FA turnover, particularly its regulation by autophagy. This study introduces a novel tandem fluorescence reporter capable of tracking the entire FA-phagy flux, from autophagosome formation to lysosomal degradation. The reporter, based on a red–green fluorescence system with a lysosome-specific cleavage site, integrates seamlessly into endogenous focal adhesion complexes, demonstrating sensitivity and specificity to autophagy stimuli. Validated in multiple cell lines, the tool revealed dynamic FA-phagy responses to …

Genome And Transcriptome-Wide Analyses Identify Multiple Candidate Genes And A Significant Polygenic Contribution In Bicuspid Aortic Valve, Sébastien Thériault, Jacob A Holdcraft, Dinara Sharipova, Adèle Faucherre, Radoslaw M Debiec, Baravan Al-Kassou, Elena Ashikhmina Swan, Andrea Ballotta, Michele Bellino, Hanna M Björck, Anne Sophie Boureau, Peter S Braund, François Corriveau, François Dagenais, Lasse Folkersen, Amalia Forte, Michael D Francke, Alessandro Frigiola, Svetlana Gorbatov, Dongchuan Guo, Karam M Habchi, Mahyar Heydarpour, Eric M Isselbacher, Chris Jopling, Fabien Laporte, Solena Le Scouarnec, Zhonglin Li, Peter Lichtner, Carlo Maj, Hasanga D Manikpurage, Christopher P Nelson, Thy B Nguyen, Russell A Norris, Chin Siang Ong, Philippe Pibarot, Tanmoy Roychowdhury, Berardo Sarubbi, Floriane Simonet, Thoralf Sundt, Ida Surakka, Idit Tessler, Cristen J Willer, Susanne Wittmann, Bo Yang, Igor Berezovets, Stefanie A Doppler, Martina Dreßen, Katharina Knoll, Thomas Puehler, Heribert Schunkert, Jean-François Avierinos, Malenka M Bissell, Aidan P Bolger, Yohan Bossé, Eduardo Bossone, María Brion, Rodolfo Citro, Carlo De Vincentiis, G Michael Deeb, Alessandro Della Corte, Christian Dina, Ronen Durst, Stephan Ensminger, Per Eriksson, Arturo Evangelista, Anders Franco-Cereceda, Dan Gilon, Betti Giusti, Simon L Hetherington, Gordon S Huggins, Markus Krane, Thierry Le Tourneau, Giuseppe Limongelli, Patrick Mathieu, David Messika-Zeitoun, Hector I Michelena, Dianna Milewicz, Jochen D Muehlschlegel, David R Murdock, Georg Nickenig, Stefano Nistri, Markus M Nöthen, Francesca Pluchinotta, Siddharth K Prakash, Nilesh J Samani, Jean-Jacques Schott, Tom R Webb, Stéphane Zaffran, Salim Abdelilah-Seyfried, Kim Eagle, Johannes Schumacher, Teresa Trenkwalder, Simon Body

Faculty, Staff and Student Publications

Background: Bicuspid aortic valve (BAV) is a frequent congenital heart defect with a high heritability. Despite this, only a limited number of genes have been associated with the disease, and the molecular mechanisms remain unexplained in most cases. This study aimed to further understand the genetic architecture of BAV.

Methods: A genome-wide association study meta-analysis including 9631 cases among 65 677 participants was performed. Genes were prioritized using transcriptomic analyses based on RNA sequencing in relevant tissues, including human fetal and adult aortic valves. The impact of the knockdown or knockout of 4 candidate genes on cardiac development was verified …

Overcoming Host Restrictions To Enable Continuous Passaging Of Gii.3 Human Norovirus In Human Intestinal Enteroids, Anil Surathu, B Vijayalakshmi Ayyar, Carmen V Apostol, Hoa Nguyen Phuc, Khalil Ettayebi, Aaya Boussattach, Xi-Lei Zeng, Sarah E Blutt, Harsha Doddapaneni, Donna M Muzny, Cristian Coarfa, Ramakrishnan Anish, B V Venkataram Prasad, Robert L Atmar, Sasirekha Ramani, Mary K Estes

Faculty, Staff and Students Publications

The establishment of human intestinal enteroids (HIEs) as a model for human norovirus (HuNoV) replication has been transformative for studying this leading cause of gastroenteritis. However, indefinite passaging of HuNoVs in HIEs remained a challenge, necessitating the use of patient stool samples as viral inocula. Using RNA-seq, we identified CXCL10, CXCL11, and CCL5 as up-regulated chemokines, suggesting their potential as host restriction factors. TAK-779, a CXCR3/CCR5/CCR2 antagonist, enhanced GII.3 HuNoV replication and viral spread in a dose- and time-dependent manner, enabling successful passaging of GII.3 HuNoV in two different HIE lines and generation of viral stocks. Sequencing passaged virus revealed …

Investigating The Oncogenic Role Of Aberrant Ezh2 In Hepatoblastoma, Brian T Hickner, Priyanka Rao, Roma H Patel, Andrew A Badachhape, Somak Roy, Emily Schepers, Nikolai A Timchenko, James I Geller, Sarangarajan Ranganathan, Gregory M Tiao, Bruce Aronow, Takanori Takebe, Sarah E Woodfield, Sanjeev A Vasudevan, Alexander J Bondoc

Faculty, Staff and Students Publications

Hepatoblastoma (HB) is the most common pediatric liver malignancy. However, its cellular origin and molecular drivers remain poorly defined. Using single-nuclear RNA sequencing (snRNA-seq), we identified a proliferative, hepatocyte-derived tumor cell population (cycling HepT) enriched for Enhancer of Zeste Homolog 2 (EZH2) expression, particularly in the aggressive embryonal subtype. Integrative genomic and transcriptomic profiling confirmed EZH2 overexpression. Disruption of the PRC2 complex was evident through mislocalization and reduced expression of SUZ12, a core component. EZH2 overexpression correlated with upregulation of mitotic regulators such as AURKB and Ki67 in human HB gene expression analysis as compared to background liver. Targeted sequencing …

Defining Clinically Relevant Responses In Erectile Function: An Smsna Position Statement, Mohit Khera, Raymond C Rosen, Petar Bajic, Helen Bernie, Martin Gross, Johanna Hannan, Sevann Helo, Lawrence Jenkins Ii, Carol Podlasek, Daniel Watter, Matthew Ziegelmann, Tobias Köhler

Faculty, Staff and Students Publications

Background: To date, no scoring system has adequately defined clinical efficacy of erectile dysfunction (ED) therapies when evaluating differences between cohorts or in meta-analytic studies.

Aim: To outline the minimal criteria required for any therapy to be considered clinically effective in the treatment of ED.

Methods: An analytic review was performed of standardized ED questionnaires, with a particular emphasis placed on the International Index of Erectile Function, Erectile Function Domain (IIEF-EFD), and the minimally clinically important difference (MCID) concept. The data were used to create a societal position statement and recommendations on best practices within clinical trials to determine treatment …

Extracellular Matrix Mediates Circulating Tumor Cell Clustering In Triple-Negative Breast Cancer Metastasis, Rong Zheng, Gad Shaulsky, Matthew J Ellis, Chonghui Cheng

Faculty, Staff and Students Publications

Metastatic tumor cell dissemination is the leading cause of cancer-related deaths. Clustered circulating tumor cells (CTCs) possess higher metastatic potential than single CTCs. Epithelial adherens junction (AJ) proteins typically mediate stable cell-cell interactions; however, these proteins are frequently lost in highly aggressive triple-negative breast cancers (TNBCs), raising the question of how CTCs from such tumors cluster. Here we show that the extracellular matrix (ECM) component hyaluronan (HA) mediates AJ-independent CTC clustering in TNBCs. HA is necessary and sufficient to drive clustering of tumor cells expressing its receptor CD44. Mechanistically, HA initiates contact between neighboring cells through actin-based membrane protrusions. As …

Improving Prediction Accuracy Of Radiation-Induced Temporal Lobe Injury In Nasopharyngeal Carcinoma Using Adc-Based Deep Learning And Dosiomics, Junyi Liu, Jiawei Zhou, Han Gao, Hongliang Yu, Yinsu Zhu, Baozhou Sun, Guanyu Yang, Shengfu Huang, Lirong Wu, Li Sun, Xia He

Faculty, Staff and Students Publications

Background: To investigate the potential of apparent diffusion coefficient (ADC) map-based deep learning and dose distribution-based dosiomics in predicting radiation-induced temporal lobe injury (RTLI) in nasopharyngeal carcinoma (NPC).

Methods: This retrospective study included 3578 NPC patients from Jiangsu Cancer Hospital receiving intensity-modulated radiation therapy (IMRT). Ninety-four RTLI patients were recruited based on inclusion criteria and matched 1:1 with 97 control subjects using propensity scores. Patients were randomly assigned to the training cohort (n = 135) and the validation cohort (n = 59). Deep transfer learning (DTL) features and dosiomics features were extracted from ADC map and three-dimensional dose distribution, respectively. …

Commentary On “Ultrasound Evaluation Of Left Ventricular Function In Coronary Artery Ectasia: The Added Value Of 2d Speckle-Tracking Echocardiography”, Eman Aslam, Maryam Amjad

Journal of the Saudi Heart Association

No abstract provided.

A Glimpse Of Liver Resection Profile In An Indonesian Tertiary Hospital: A Retrospective Descriptive Study, Florencia V. Vaniara, Arnetta Nl Lalisang, Toar Jm Lalisang, Yarman Mazni, Agi S. Putranto, Wifanto S. Jeo, Febiansyah Ibrahim, Ridho A. Syaiful, Lam Sihardo, Vania Mg Marbun

The New Ropanasuri Journal of Surgery

Introduction. In-depth liver resection profile is needed for evaluation to improve the procedure’s outcome. This study aims to describe the clinical characteristics and outcomes of liver resection in HCC patients in Cipto Mangunkusumo Tertiary Hospital.

Methods. This study retrospectively analyzed the clinical data of 19 HCC patients who underwent liver resection in Cipto Mangunkusumo Tertiary Hospital from 2021 to 2024. Demographic, clinical, laboratory, operative, and pathological data were collected. Postoperative complications were assessed using the Clavien-Dindo classification system within 30- and 90-day postoperative periods.

Result. Nineteen patients were included, comprising 12 (63.2%) males and 7 (36.8%) females. Sixteen patients (84.2%) …

Management Of Gastrointestinal Tract Arteriovenous Malformations In Adults: A Literature Review, Febiansyah Ibrahim, Angie Beatrice

The New Ropanasuri Journal of Surgery

Introduction. Arteriovenous malformations (AVMs) of the gastrointestinal (GI) tract are rare vascular lesions that can cause significant GI bleeding, posing a diagnostic challenge in clinical practice. This literature review examines the management strategies for AVMs in adults, focusing on identifying optimal treatment approaches and minimizing recurrence, particularly in Indonesia where no standardized treatment guidelines are available.

Method. A literature search was conducted from August 24, 2022, to September 11, 2023, using PUBMED®, Cochrane®, Proquest®, and Scopus® databases. The inclusion criteria were studies published in English or Indonesian within the last 25 years, including case series, cohort studies, or systematic reviews …

The Outcome Of Snare Loop Catheter For Foreign Body Removal In Superior Vena Cava: An Evidence-Based Case Report, Hutomo Rezky Noorsukma, Patrianef Darwis

The New Ropanasuri Journal of Surgery

Introduction. In recent years, the utilization of central venous catheters (CVC) in medical practice has become increasingly common. One of the complications associated with central venous catheterization is embolization of catheter fragments, which arefound in 1% of cases. Currently, endovascular techniques, such as snare loop catheter, have been developed for the extraction of intravascular foreign bodies. However, there is no strong evidence regarding this method. Thisliterature review aims toevaluate the efficacy and safety of snare loop catheters for foreign body removal within the superior vena cava (SVC).

Method. We searched four databases, that is Cochrane, PubMed, EBSCO, and …

Roux-En-Y Duodenojejunostomy As Surgical Treatment For Congenital Duodenal Obstruction: A Case Report, Ahmad Yani, Albireza Ruhimat

The New Ropanasuri Journal of Surgery

Introduction. Congenital duodenal obstruction is an anatomical abnormality in newborns. Various intrinsic and extrinsic etiologies can cause duodenal obstruction. The surgical treatment that is commonly performed on duodenal obstruction in neonates is duodenoduodenostomy. However, several etiological conditions, such as preduodenal portal vein (PDPV) and pancreatic annulare cause duodenoduodenostomy nearly impossible to perform, so an alternative surgery procedure with a good outcome is necessary.

Case Illustration. A female neonate had been suspected congenital duodenal obstruction since pregnancy due to polyhydramnios. An OGT was inserted with greenish yellow residue after the baby was born. Based on abdominal x-ray examination, a …

Whipple Procedure For High-Grade Pediatric Pancreatic Injury After Blunt Trauma: A Case Report, David C. El Gah, Tri H. Rahayatri, Asri D. Rachmawati, Adianto Nugroho

The New Ropanasuri Journal of Surgery

Introduction: Pediatric pancreatic injury isuncommon but carries significant morbidity. While non-operative management is standard for low-grade injuries, the optimal approach for high-grade trauma (AAST grade III–V) remains debated. Pancreaticoduodenectomy (Whipple procedure) is rarely performed due to high procedural risks and is typically reserved for severe pancreatic head injury with concomitant duodenal damage.

Case presentations: A 13-year-old boy presented three days after blunt abdominal trauma with epigastric pain and bilious vomiting. CT imaging revealed free fluid, a large retroperitoneal hematoma, and suspected pancreatic head injury. Despite initial stability and conservative management in the High Care Unit, worsening abdominal distension prompted an …

Locoregional Management In Breast Cancer With Brca1/2 Mutation: Evidence Based Case Report, Adlina Karisyah, Sonar S. Panigoro

The New Ropanasuri Journal of Surgery

Introduction. Breast cancer is still one of the top health issues worldwide. Hereditary predisposition is linked with morbidity and mortality of breast cancer patients. BRCA 1/2 genetic mutation, one of mutations in breast cancer that has been extensively observed, has tremendous effects on the carrier. Studies showed that patients with BRCA1/2 mutation are often associated with poor pathological characteristics. Further research isyet to identify the effect of the mutation with prognosis including locoregional recurrences. This study aims to understand the risk of locoregional recurrences on the patients with breast cancer and BRCA 1/2 genetic mutation who had BCT or …

Comparative Analysis Of Ctdna Monitoring Strategies In Advanced Nsclc With Met Exon 14 Skipping Mutations Treated With Ensartinib, Mo Zhou, Yin Zhu, Xuqi Sun, Ying Han, Rui Jin, Jun Zhao, Zhiyuan Guo, Yongchang Zhang, Yiran Meng, Fei Liu, Wen Li, Xiuning Le, Haifeng Shen, Yang Xia

Faculty, Staff and Student Publications

Mesenchymal-epithelial transition exon 14 skipping mutations (METex14) define a targetable molecular subset of non-small cell lung cancer (NSCLC), but optimal circulating tumor DNA (ctDNA) biomarkers to guide MET tyrosine kinase inhibitor therapy remain undefined. Within the EMBRACE trial of ensartinib, we conducted a prospective biomarker analysis with plasma collected at baseline (V0) and 4 weeks after treatment initiation (V1). ctDNA was profiled using a hybrid-capture next-generation sequencing panel covering 229 cancer-related genes, and mutations were classified into three monitoring paradigms: MET-specific alterations, canonical alterations (tier I/II), and pan-alterations (any variant in any gene on the panel). Baseline ctDNA positivity rates …

Recommendations From The Blue Ribbon Panel On Fluoroscopy Safety, Dustin A Gress, M Mahesh, Kevin W Dickey, John F Angle, D Duane Baldwin, Wayne Batchelor, Christopher Davis, Deirdre Elder, R Paul Guillerman, Maged N Guirguis, David Hardwick, Carrie M Hayes, Jeremy J Heit, A Kyle Jones, Melissa Kirkwood, Andrew Kuhls-Gilcrist, Bonnie Martin-Harris, William W Mayo-Smith, Sarah E Mckenney, Richard Miguel, Donald L Miller, Eric Monroe, Kristi Moore, Thomas L Morgan, Kari J Nelson, Kathryn Petrovic, Shellie Pike, Carlos A Pino, Travis Prowant, Jonathan W Revels, Vinil Shah, Andrew Y Wang, David B Weiss, Darcy J Wolfman, Kevin A Wunderle, Jessica Zarzour, Michael E Zychowicz, Alan H Matsumoto

Faculty, Staff and Student Publications

There are many challenges associated with the safe use of fluoroscopy. These challenges include but are not limited to highly variable regulatory requirements, scope of practice concerns, inconsistent education and training, and lack of staff empowerment. Challenges are further compounded by the increasing use of fluoroscopy across a wide range of medical specialties. To facilitate consensus on how to address the issues, the ACR convened the multidisciplinary Blue Ribbon Panel on Fluoroscopy Safety (BRP-FS), with 32 organizations represented. The goal of the BRP-FS is to establish multi- and interspecialty consensus standards for the safe use of fluoroscopy in health care, …

Phase I Study Of Bevacizumab And Temsirolimus Combination Therapy In Advanced Malignancies: Safety, Efficacy, And Ovarian Cancer Expansion, Sarina A Piha-Paul, Chieh Tseng, Emily Thompson, R Jason Stafford, Hung Le, Siqing Fu, George Blumenschein, Jordi Rodon Ahnert, John M Slopis, David Hong, Aung Naing, Funda Meric-Bernstam, Chaan S Ng, Shannon Westin, Anil K Sood

Faculty, Staff and Student Publications

Background: Bevacizumab and temsirolimus target angiogenic and mTOR pathways in cancer progression.

Methods: This phase I study enrolled 48 heavily pretreated patients with advanced solid tumors, including an ovarian cancer expansion cohort. Patients received bevacizumab biweekly plus temsirolimus weekly in a 3 + 3 design to assess safety, maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs). Exploratory analyses included tumor genomic profiling and dynamic contrast-enhanced MRI (DCE-MRI).

Results: Patients had a median age of 59 and median four prior therapies. Common tumor types were ovarian (27%) and head and neck (15%). Treatment-related adverse events occurred in 93.8%, with 31.3% ≥grade …

Pain Prevalence And Pain Management At The End Of Life: Regional And Urban-Rural Differences From A National-Representative Survey Of Chinese Older Adults, Yaolin Pei, Xiang Qi, Zexi Zhou, Yifan Lou, Jing Wang, Bei Wu

Faculty, Staff and Student Publications

Background: Effective pain management is essential for improving quality of life at the end of life. However, challenges persist globally, particularly in China, where palliative care remains underdeveloped. This study investigates pain prevalence and the associations between pain severity, place of death, and the quality of pain management among older adults in China, with a focus on regional and urban-rural disparities.

Methods: We used data from the 2014, 2016, 2018, and 2020 waves of the China Longitudinal Aging Social Survey. The final sample included 1,525 older adults who died during the study period. We conducted OLS regression analyses to examine …

The Setd2 L1609p Mutation Found In Leukemia Disrupts Methyltransferase Activity And Reduces Histone H3k36 Trimethylation, Christina Michail, Jérémy Berthelet, Ariel E Mechaly, Linh-Chi Bui, Haopeng Yang, Amira Al Mahi, Valeria Bisio, Valentina Sirri, Jean-Marie Dupret, Fabien Guidez, Ximing Xu, Nicolas Joly, Leslie Regad, Mireille Viguier, Frédérique Deshayes, Nicolas Dulphy, Michael R Green, Ahmed Haouz, Fernando Rodrigues Lima

Faculty, Staff and Student Publications

SETD2 is the primary methyltransferase responsible for generating H3K36me3, an epigenetic mark that is essential for transcriptional regulation and chromatin integrity. SETD2 mutations are frequently observed in various cancers and tend to cluster within its catalytic SET domain. Despite the clinical relevance of SETD2 missense mutations in cancer, their biochemical and structural consequences remain insufficiently characterized. Here, we present the enzymatic and structural characterization of the SETD2 L1609P mutant enzyme identified in leukemia. The L1609 residue is located in the SET domain within a conserved hydrophobic pocket that is involved in substrate H3K36 recognition. Interestingly, site-directed mutagenesis of residues within …

Endothelial Oncogenic Kras Mutation Drives The Dynamics Of Microglia And Macrophages In Brain Arteriovenous Malformation, Hyejin Park, Jung-Eun Park, Bridger H Freeman, Bosco Seong Kyu Yang, Shun-Ming Ting, Jude Pj Savarraj, Jakob Körbelin, Huimahn Alex Choi, Sean P Marrelli, Jaroslaw Aronowski, Peng Roc Chen, Eunhee Kim, Eun S Park

Faculty, Staff and Student Publications

Mutation of KRAS in endothelial cells (KRAS-EC) leads to intracerebral hemorrhage (ICH) in brain arteriovenous malformations (bAVM), resulting in severe disabilities or even death. However, it is unclear what causes this hemorrhagic conversion of bAVM. Here, using a locally established, clinically-relevant sporadic bAVM mouse model, created by overexpressing mutant KRAS (KRASG12V) in the brain EC, we demonstrate that KRAS-EC act as trigger for microglia (MG) activation and infiltration of macrophages (Mϕ). Using three-dimensional immunostaining approach with cleared human and mouse bAVM tissues, we demonstrate an abundance of MG/Mϕ around the bAVM nidus. The presence of MG/Mϕ are correlated to the …