Medical Specialties Commons^™

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, Gina M Peloso, Baravan Al-Kassou, Sary Aranki, 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 …

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

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 …

Improving Prediction Accuracy Of Radiation-Induced Temporal Lobe Injury In Nasopharyngeal Carcinoma Using Adc-Based Deep Learning And Dosiomics, Li Wang, Yang Li, Ting Qiu, 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. …

Defining Clinically Relevant Responses In Erectile Function: An Smsna Position Statement, Landon Trost, Faysal Yafi, Alan Shindel, 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 …

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 …

Transient Protein Structure Guides Surface Diffusion Pathways For Electron Transport In Membrane Supercomplexes, Chun Kit Chan, Jonathan Nguyen, Corey F Hryc, Chitrak Gupta, Kevin Redding, William Dowhan, Matthew L Baker, Alberto Perez, Eugenia Mileykovskaya, Abhishek Singharoy

Faculty, Staff and Student Publications

The exact biological role of mitochondrial supercomplexes remains debated, particularly their role in guiding redox proteins across membranes during energy conversion. We integrate multiscale modeling and single particle cryo-electron microscopy (cryo-EM) to examine electron transfer in mitochondrial supercomplexes composed of complexes III and IV (CIII and CIV). Using bioinformatic and entropy-based methods, we generated structural ensembles capturing conformations of CIII's disordered QCR6 hinge within the yeast CIII2CIV2 supercomplex. Molecular and Brownian Dynamics simulations reveal that these negatively charged hinge states electrostatically couple with redox proteins, promoting their binding and directional diffusion across the membrane on millisecond timescales. Rather than hindering …

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, Duo Cai, Amira Al Mahi, Aowei Xie, 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 …

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, Lei Kang, Siqing Fu, Apostolia Tsimberidou, 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 …

Zingiber Officinale-Mediated Zinc Oxide Nanoparticles: Antimicrobial Activity Against Multidrug-Resistant Bacteria, Maureen Bakor Tabe, Ovgu Isbilen, Jennifer N Walker, Ender Cinar

Faculty, Staff and Student Publications

Background: The fight against infectious diseases has transformed over the past century with the emergence of multidrug-resistant bacteria, where pathogens that exhibit resistance to multiple antibiotic classes leading to significant challenges to modern medicine. Zingiber officinale is well-documented to exhibit diverse biological activities, including strong antioxidant, antimicrobial, and anti-neuroinflammatory effects. Zinc oxide nanoparticles can be synthesized cost-effectively and are widely utilized in biomedical applications, including their use as anticancer agents and drug-delivery systems, as well as for their intrinsic antibacterial and anti-inflammatory properties. In this study, we aimed to take a combinatorial approach to investigate the antimicrobial effects of Z. …

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, Yang Li, 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 …

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, Panwen Tian, Jun Zhao, Yang Jin, 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, Stephen Balter, Wayne Batchelor, Lisa Bruedigan, 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, …

Identification Of A Cytokine Biomarker For Prognostic Modeling Of Breast Cancer-Related Lymphedema, Alison J Wu, Neil Lin, Jie Su, Cherie Lin, Madison-Shira Hossack, Wei Shi, Farnoosh Abbas-Aghababazadeh, Wei Xu, Benjamin Haibe-Kains, Simona F Shaitelman, Melissa B Aldrich, Fei-Fei Liu, Jennifer Y Y Kwan

Faculty, Staff and Student Publications

Lymphedema is a chronic complication of breast cancer treatment, and early intervention is crucial to reduce morbidity. This study evaluated the role of blood-based cytokine biomarkers in the prognostication of breast cancer-related lymphedema (BCRL) to improve risk prediction. A secondary analysis of inflammatory biomarkers for BCRL was performed using a previously published cohort of 147 breast cancer patients who had undergone serum cytokine profiling during their treatment at the Princess Margaret Cancer Centre from 2010-2014. Prognostic cytokine variables for lymphedema were selected by regression analysis and independence from known clinical risk factors. Regression-based modeling was employed to integrate prognostic variables …

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, Alexander K Suh, Jude Pj Savarraj, Shuning Huang, 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 …

Effects Of Bungee-Based Training On Physical Performance And Arch Jump Kinematics In Female College Rhythmic Gymnasts, Nasser Abouzeid, Mariola Gepfert, Abdulrahman I. Alaqil, Abdulmalek K. Bursais, Hussein Hashoos, Mohammed S. Alibrahim, Labeeb Z. Moseekh, Amr S. Hamza

Baltic Journal of Health and Physical Activity

Background: The purpose of this study was to examine the effects of an eight-week bungee-based training program on selected physical performance variables and arch jump kinematics in female college rhythmic gymnasts. Material and methods: Eighteen female college students (age: 18.1 ± 0.9 years) were randomly assigned to an experimental group (EG; n = 9) or a control group (CG; n = 9). The EG completed a bungee workout training program three times per week for eight weeks, while the CG followed a traditional rhythmic gymnastics training program. Physical performance variables included vertical jump, leg strength, back strength, standing long jump, …

The Heart’S Hidden Influencer: Epicardial Adipose Tissue In The Pathogenesis Of Heart Failure, Aobo Li, Avilash Mondal, Jianli Zhao, John Zhang, Xin-Liang Ma

Department of Emergency Medicine Faculty Papers

Abstract – Heart failure (HF) is a complex, multifactorial clinical syndrome with diverse etiologies and phenotypic manifestations, affecting millions of people globally. HF is broadly classified into 3 subtypes: HF with reduced ejection fraction, HF with mildly reduced ejection fraction, and HF with preserved ejection fraction. Each subtype exhibits distinct pathophysiological mechanisms, clinical trajectories, and therapeutic responses, posing significant challenges in terms of diagnosis and management. Epicardial adipose tissue (EAT), a metabolically active visceral fat depot situated in close proximity to the myocardium, plays a dual role in physiological and pathological states, offering potential utility as a biomarker and therapeutic …

Assessing Social Determinants Of Health Training In Graduate Medical Education: A Narrative Review Using Kirkpatrick’S Model, Surya Namboodiri, Bharathi Gadad, Juan Lopez-Alvarenga, Chelsea Chang

School of Medicine Publications

Social determinants of health (SDOH) training is a critical component of medical education, equipping physicians to address factors such as economic stability, education, and health care access. Despite its importance, the evaluation of SDOH training often focuses on lower-level outcomes, such as learner satisfaction and knowledge assessment, with limited emphasis on behavioral change and patient outcomes. Kirkpatrick’s model offers a validated framework for addressing this gap by categorizing training outcomes into four levels: Reaction, Learning, Behavior, and Results.

By applying Kirkpatrick’s model in combination with Grading of Recommendations Assessment, Development and Evaluation (GRADE) quality assessment and bibliometric network analysis, this …

Ubiquitination Of Oncogenic Mutant P53 Via Attenuation Of Ribosome Biogenesis Machinery Effectively Inhibits Pancreatic Tumor Growth, Mudassier Ahmad, Sahir Sultan Alvi, Haider Ahsan, Carlos Perez, Andrew Massey, Vivek K Kashyap, Neeraj Chauhan, Emmanuel Anning, Manish K Tripathi, Dae J Kim, Nirakar Sahoo, Tamer Oraby, Murali M Yallapu, Mohammad Moshahid Khan, Manu M Sebastian, Subhash C Chauhan, Bilal B Hafeez

Faculty, Staff and Student Publications

Dysregulated ribosome biogenesis and p53 mutations are known to play oncogenic roles in various cancers, including pancreatic cancer. In this study, we demonstrated the therapeutic potential of BMH-21, a pharmacologic inhibitor of RNA polymerase I, against pancreatic cancer by uncovering a novel molecular mechanism involving RPA194-mediated ubiquitination of mutant p53 without affecting the ubiquitination of wild-type p53. Our key findings are that (i) BMH-21 selectively induces apoptosis and cell growth inhibition of pancreatic cancer cells with no effect on normal human pancreatic ductal epithelial cells; (ii) BMH-21 degrades RPA194; (iii) BMH-21 inhibits recruitment of both RPA194 and RPA135 on rDNA …

The Next Layer: Augmenting Foundation Models With Structure-Preserving And Attention-Guided Learning For Local Patches To Global Context Awareness In Computational Pathology, Muhammad Waqas, Rukhmini Bandyopadhyay, Eman Showkatian, Amgad Muneer, Anas Zafar, Frank R Alvarez, Maricel Corredor Marin, Wentao Li, David Jaffray, Cara Haymaker, John V Heymach, Natalie Vokes, Luisa M Solis Soto, Jianjun Zhang, Jia Wu

Faculty, Staff and Student Publications

Foundation models have emerged as powerful feature extractors in computational pathology. However, they typically omit mechanisms for leveraging the global spatial structure of tissues and the local contextual relationships among diagnostically relevant regions-key elements for understanding the tumor microenvironment. Multiple instance learning (MIL) remains an essential next step following the foundation model, designing a framework to aggregate patch-level features into slide-level predictions. We present EAGLE-Net, a structure-preserving, attention-guided MIL architecture designed to augment prediction and interpretability. EAGLE-Net integrates multi-scale absolute spatial encoding to capture global tissue architecture, a top-K neighborhood-aware loss to focus attention on local microenvironments, and background suppression …

Tumor Radiosensitization With Gold Nanoparticles: Evolving Strategies To Improve Tumoral Gold Uptake And Catalyze Future Clinical Translation, Prapannajeet Biswal, Geraldine V Vijay, Gabrielle Krouse, Phuoc Minh Quan Mai, Bhoomika Muruvekere Lakshmisha, Sanaz Keshavarz Shahbaz, Mahdieh Yousefi Taba, Aria Sabbagh, Lydia Wt Cheung, Yuri Mackeyev, Khadijeh Koushki, Sunil Krishnan

Faculty, Staff and Student Publications

Radiation therapy is integral to the treatment regimens of over 50% of cancer patients. However, it is not biologically targeted to just the tumor, leading to adverse effects in peritumoral normal tissue. Selective uptake of gold nanoparticles (AuNPs) by tumors realizes tumor-specific radiosensitization via increased secondary electron release from high atomic number gold atoms. Here, we review AuNP-mediated radiosensitization and outline strategies to optimize tumor-targeted AuNP delivery. Modifying the physicochemical characteristics of AuNPs, including size, shape, charge, and surface chemistry, can increase their ability to evade the reticuloendothelial system (RES) and penetrate the dense tumor stromal architecture, thereby promoting tumor …

Repurposing Of The Macrolide Antibiotic Clarithromycin For The Prevention Of Lung Cancer, Shanshan Deng, Tabish Hussain, Thais F Bartelli, Manu M Sebastian, Melody Zarghooni, Walter V Velasco, Brandon Somerville, Linda Phan, Michelle I Savage, Yurong Song, John L Clifford, Humam Kadara, Florencia Mcallister, Powel H Brown, Seyed Javad Moghaddam, C Marcelo Aldaz

Faculty, Staff and Student Publications

Drug repurposing is the process of reusing existing pharmaceuticals for novel clinical purposes, which offers advantages such as streamlined clinical trial access and reduced drug development costs. Clarithromycin (CAM), a member of the macrolide antibiotics family, is a promising candidate for repurposing in cancer therapy due to its known preclinical and clinical immunomodulatory and anticancer properties. In the current study, we investigated whether CAM could be repurposed as a preventive treatment for KRAS-mutant lung cancer, a subtype of lung adenocarcinoma that is strongly associated with heavy smoking. CCSPCre; LSL-KrasG12D mice at an early stage of tumor development were treated with …

Two Faces Of Mitral Stenosis: Uncovering Structural And Hemodynamic Signatures Of Rheumatic And Mitral Annular Calcification-Induced Disease, Mohammad S. Hashemi, Peter Abdelmaseeh, Atif Nehvi, Gregg S. Pressman, Arash Kheradvar

Einstein Health Papers

BACKGROUND: Mitral annular calcification (MAC) is common and associated with increased cardiovascular risk and, when severe, mitral stenosis (MS). MAC-related MS differs anatomically and hemodynamically from rheumatic MS (RMS), challenging standard diagnostic methods. This study compares structural and flow characteristics, including  kinetic energy losses, across MAC-related MS, RMS, and normal mitral valves, and evaluates the applicability of conventional diagnostic metrics in MAC.

METHODS: Three-dimensional transesophageal echocardiographic data sets from 70 patients (22 normal mitral valves, 26 RMS valves, 22 MAC valves) were used to obtain linear, area, and volumetric measurements for valve comparison. Representative valves from each group were converted …

An Autopsy Case Of Extensive Aortic Thrombosis With Acute Kidney Injury As The Sole Clinical Manifestation, Risa Suenaga, Makoto Fukuda, Atsuhiko Suenaga, Yuki Ikeda, Maki Yoshihara, Megumi Nishiyama, Seiichi Kato, Motoaki Miyazono

Children’s Nutrition Research Center Staff Publications

Aortic thrombosis is a rare but life-threatening condition. It typically presents with abdominal or lower-limb ischemia. Although acute kidney injury (AKI) can accompany aortic thrombosis, AKI as the sole clinical manifestation has not been previously reported. A 69-year-old man with extensive atherosclerotic disease and chronic kidney disease presented with severe oliguria. Initial evaluation, including non-contrast computed tomography (CT), did not reveal any aortic abnormalities. Renal Doppler ultrasonography findings and markedly elevated D-dimer levels prompted contrast-enhanced CT, which demonstrated extensive thrombus formation extending from the descending thoracic aorta to the bilateral iliac arteries, with complete occlusion of both renal arteries and …

Proceedings From The Inaugural Conference On The Science Of Cancer Health Equity For Sexual And Gender Minority (Sgm) Communities, Charles S Kamen, Milena E Insalaco, Richard Brown, Chasity Burrows Walters, Shine Chang, Viktor Clark, Jason Domogauer, Lauren V Ghazal, Kelly Haviland, Forrest Hosea, Nelson Sanchez, Matthew B Schabath, Zul Surani, Gwendolyn P Quinn

Faculty, Staff and Student Publications

Purpose: Sexual and gender minority people (SGM) experience multiple cancer-related disparities, including higher rates of cancer risk factors, lower rates of cancer screening, higher lifetime risk of cancer, and unmet needs throughout cancer survivorship. Although many national organizations, including the National Cancer Institute (NCI) and the American Cancer Society (ACS), have emphasized the need for more cancer research among SGM communities, currently no consensus exists about the highest research priorities, promising research models, or mechanisms to support collaboration between geographically dispersed scientific teams.

Methods: To address this gap, we convened a three-day conference to focus on the "Science of Cancer …