Digital Commons Network^™

Reliability Of Handheld Autorefractometers In Patients After Cataract Surgery ​, Ayça Küpeli̇ Çinar, Abdulkadi̇r Can Çinar, Hande Güçlü

Turkish Journal of Medical Sciences

Background/aim: Accurate postoperative refraction assessment is essential for optimal visual rehabilitation after cataract surgery. Although handheld autorefractometers (HH-ARMs) are widely used in pediatric and uncooperative patients, their reliability in adults after cataract surgery remains uncertain. This study compared refractive outcomes obtained with a HH-ARM (Mediworks V100; Mediworks, Guangzhou, China) and a TB-ARM (Canon RK-F2; Canon Inc., Tokyo, Japan) to evaluate the clinical applicability of HH-ARM in this population.

Materials and methods: This prospective study included 150 eyes of 150 patients (aged 55–85 years) who underwent uncomplicated phacoemulsification with intraocular lens (IOL) implantation. At 1 month postoperatively, spherical value (SV), cylindrical …

A Social Media Campaign And Web-Based Survey About Prostate Cancer Genetics: Mixed Methods Study, Amy Leader, Stacy Loeb, Preethi Selvan, Ashley Hunter, Rebecca Hartman, Scott Keith, Veda Giri

Department of Medical Oncology Faculty Papers

BACKGROUND: Germline genetic variants are important for prostate cancer (PCa) management and hereditary cancer risk assessment, but testing is underused. Furthermore, patients are often unaware of the genetic connections to PCa. Social media is increasingly serving as a source of awareness for health information and a method to gather data from a large population.

OBJECTIVE: There were three objectives: to (1) create and test social media messages related to PCa genetics and genetic testing, (2) determine which social media message was most engaging, and (3) assess knowledge of and attitudes toward PCa genetic testing through an online survey using the …

Current Insights On Predicting Vestibular Diseases Using Machine Learning, Emre Söylemez, Muhammed Mustafa Şeker

Turkish Journal of Medical Sciences

The vestibular system is one of the three main systems responsible for maintaining balance and posture. Accurate vestibular inputs enable the perception of the head’s position and movement in space, and ensure coordination between head movements, eye movements, balance, and posture. Any dysfunction in the peripheral vestibular end organs, the vestibular nerve, or the central vestibular system may lead to vertigo, dizziness, and gait disturbances in individuals. Some syndromes that cause vertigo symptoms can be life threatening. Although peripheral vestibular pathologies are generally benign, they can reduce patients’ quality of life, cause falls, and hinder independence. Therefore, the diagnosis and …

A Randomized Controlled Prospective Study Comparing Surgical Outcomes Of Median Umbilical Ligament Lift-Up And Veress Needle Entry Techniques In Gynecologic Laparoscopic Surgery, Gazi̇ Güner, Ayşe Bacaksiz, Can Berk Karabudak, Fi̇gen Efe Çami̇li, Çi̇sem Ertok, Si̇nem Özşahi̇n Kiliç, Zeli̇ha Zeynep Satilmişoğlu, Can Tercan, Nazli Ayli̇n Vural

Turkish Journal of Medical Sciences

Background/aim: Laparoscopic surgery has become the preferred minimally invasive technique for both diagnostic and therapeutic procedures in gynecology. Although it is associated with lower overall complication rates compared to open surgery, most serious complications occur during the initial step of abdominal entry. Therefore, developing faster and safer entry methods is critical to improving surgical outcomes. This study aimed to compare the surgical results of the Median Umbilical Ligament Lift-Up (MULU) technique routinely used in our clinic with the commonly preferred Veress needle (VN) entry technique.

Materials and methods: This randomized, controlled, prospective study included 124 patients: 64 underwent abdominal entry …

Hesperidin Efficacy Of Epidural Fibrosis In A Post Laminectomy Rat Model: An Experimental Study, Emrah Keski̇n, Mehmet Seli̇m Gel

Turkish Journal of Medical Sciences

Background/aim: Epidural fibrosis (EF) plays a significant role in the development of failed back surgery syndrome (FBSS). This study evaluates the antifibrotic effect of hesperidin, a citrus-derived bioflavonoid, within a rat laminectomy model.

Materials and methods: Thirty-two female Wistar albino rats were randomized into four groups (n = 8 each). Group 1 received laminectomy alone (control); Group 2 received a gelatin sponge; Groups 3 and 4 intraperitoneally received 50 mg/kg and 100 mg/kg of hesperidin, respectively, for 7 days post-laminectomy. After 6 weeks, epidural tissues were assessed histopathologically, and hydroxyproline levels were measured.

Results: Group 4 showed significantly lower EF …

Assessment Of Alterations In Regional Homogeneity And Amplitude Of Low-Frequency Fluctuations In Children With Dyslexia ​, Esra Demi̇rci̇, Şeri̇fe Gengeç Benli̇, Semra İçer, Zeynep Ak, Ebru Aker, Zehra Fi̇li̇z Karaman

Turkish Journal of Medical Sciences

Background/aim: Exploratory methods in neuroimaging are gaining increasing attention for revealing functional connectivity structures across the entire brain. This study aims to contribute to the understanding of the functional mechanisms underlying dyslexia, along with the effects of specialized education for dyslexia treatment, by utilizing measures such as regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF), and fractional ALFF (fALFF).

Materials and methods: Resting-state functional magnetic resonance imaging data were collected from three groups of Turkish-speaking children aged 7–12: diagnosed with dyslexia for the first time (Dys, n = 19), children with dyslexia who received specialized education (EDys, n = 20), …

Effects Of Olfaction On Sexual Function, Anxiety, Depression, And Quality Of Life In Men And Women With Smell Disorder: A Cross-Sectional Controlled Study ​, Esi̇n Özlem Atmiş, Eser Sağaltici, Eren Yilmaz, Hasan Gökçay, Aytuğ Altundağ

Turkish Journal of Medical Sciences

Background/aim: Olfaction is necessary for healthy sexual intercourse. Better smell has been associated with a more positive sexual experience.

Materials and methods: In this cross-sectional study, 40 patients diagnosed with a smell disorder and 60 healthy volunteers were included. The participants were divided into 2 groups according to sex. The female group had 19 patients and 25 female controls. The male group had 21 patients and 35 male controls. Sniffin’ Sticks tests, the World Health Organization quality of life assessment (WHOQOL), and hospital anxiety and depression scale (HADS) were applied to all participants. In addition, the international index of erectile …

Ai Performance In Emergency Medicine Fellowship Examination: Comparative Analysis Of Chatgpt-4o, Gemini 2.0, Claude 3.5, And Deepseek R1 Models, İshak Şan, Medi̇ne Akkan Öz, Mehmet Yortanli, Murat Genç, Bensu Bulut, Ayşenur Gür, Rami̇z Yazici, Hüseyi̇n Mutlu, Mustafa Önder Gönen

Turkish Journal of Medical Sciences

Background/aim: This study evaluated the accuracy rates and response consistency of four different large language models (ChatGPT- 4o, Gemini 2.0, Claude 3.5, and DeepSeek R1) in answering questions from the Emergency Medicine Fellowship Examination (YDUS), which was administered for the first time in Türkiye.

Materials and methods: In this observational study, 60 multiple-choice questions from the Emergency Medicine YDUS administered on 15 December 2024, were classified as knowledge-based (n = 26), visual content (n = 2), and case-based (n = 32). Each question was presented three times to the four large language models. The models’ accuracy rates were evaluated according …

The Effect Of Beverages And Cleansers On The Color Stability And Surface Roughness Of Conventional And Digital Denture Base Resins ​, Zeynep Şahi̇n, Nazi̇re Esra Özer, Mehmet Ali̇ Kiliçarslan

Turkish Journal of Medical Sciences

Background/aim: Research on the optical and surface properties of 3D-printed denture base materials is limited. This study investigated the effects of different beverages and denture cleansers on the color stability and surface roughness of conventional and digital denture bases.

Materials and methods: A total of 240 specimens were prepared using two digital (CAD/CAM milling and 3D printing) and two conventional (cold- and heat-polymerized) materials. The specimens were immersed in tea, coffee, and artificial saliva for 12 days. After immersion, specimens were cleaned with either sodium hypochlorite or a Corega effervescent tablet. Color changes and surface roughness were measured with a …

Efficacy And Safety Of Low-Power Holmium Laser Enucleation Of The Prostate: Experience Gained From More Than 700 Cases ​, Bahadir Topuz, Can Si̇ci̇mli̇, Ahmet Hali̇s, Engi̇n Kaya, Sercan Yilmaz, Murat Zor, Serdar Yalçin, Selahatti̇n Bedi̇r

Turkish Journal of Medical Sciences

Background/aim: The aim of this study was to investigate the functional outcomes, safety, and effectiveness of low-power (LP) holmium laser enucleation of the prostate (HoLEP) using a 37.5 W holmium laser source.

Materials and methods: We retrospectively reviewed 713 patients with a diagnosis of benign prostatic hyperplasia (BPH) treated with HoLEP using an LP setting (37.5 W laser set to 1.5 J with a frequency of 25 Hz). All procedures were performed by experienced urologists. Functional outcomes, perioperative parameters, and complications were assessed over a 12-month follow-up period. Effect sizes (Cohen’s d) and 95% confidence intervals (CI) were calculated to …

Lumbar Disk Herniation Surgeries: The Impact Of Preoperative Holding Area Duration On Anxiety And Postoperative Pain ​, Zuhal Koç Apaydin, Hakan Kina

Turkish Journal of Medical Sciences

Background/aim: The purpose of this study is to investigate how anxiety levels are affected by preoperative holding area waiting times and how these fears affect pain following surgery. Patients waiting for surgery frequently suffer from preoperative anxiety, which can have an impact on how well they manage their postoperative pain.

Materials and methods: Forty-eight individuals with lumbar disc herniation scheduled for surgery participated in the study. Patients’ anxiety and pain levels were measured both during and after the preoperative holding area waiting period using the Amsterdam Preoperative Anxiety and Information Scale (APAIS), State-Trait Anxiety Inventory (STAI), and Visual Analog Scale …

Cultural Adaptation And Psychometric Characteristics Of The Child Oral And Motor Proficiency Scale (Chomps)-Turkish Version, Ebru Umay, Si̇bel Eyi̇gör, Damla Cankurtaran, Sema Kalkan, Ni̇hal Tezel, Cuma Uz, Şükran Güzel, Fatma Balli Uz, Güler Gözpinar, Recep Gayir, Fatma Nazli, Keri̇m Demi̇rsöz, Ece Ünlü Akyüz, Britt Pados

Turkish Journal of Medical Sciences

Background/aim: The child oral and motor proficiency scale (ChOMPS) is a parent-reported assessment that evaluates a child’s eating and drinking skills within the framework of all related motor functions. It has been found to be useful in research studies and recommended in reviews. The purpose of this study was to perform the translation and cultural adaptation of the English version of the ChOMPS to Turkish and conduct psychometric testing of the ChOMPS–Turkish version, including reliability and validity.

Materials and methods: This study was conducted with 185 children. Cronbach’s α, corrected item-to-total correlations, coefficient of variation, and Cronbach’s α when one …

Erratum To “ The Role Of Carbon Dioxide Angiography In Reducing Contrast-Induced Nephropathy In Diabetic Foot Patients Undergoing Endovascular Treatment” [Turkish Journal Of Medical Sciences 55 (4): 877-886 ], Sadik Ahmet Uyanik, Erdem Bi̇rgi̇, Saffet Öztürk, Umut Asfuroğlu, Erdi̇ Tangobay, Hi̇kmet Erhan Güven

Turkish Journal of Medical Sciences

The original article can be accessed at: https://doi.org/10.55730/1300-0144.6040

Generative Modeling For Interpretable Anomaly Detection In Medical Imaging: Applications In Failure Detection And Data Curation, Mckell E Woodland, Mais Altaie, Caleb S O'Connor, Austin H Castelo, Olubunmi C Lebimoyo, Aashish C Gupta, Joshua P Yung, Paul E Kinahan, Clifton D Fuller, Eugene J Koay, Bruno C Odisio, Ankit B Patel, Kristy K Brock

Faculty, Staff and Students Publications

This work aims to leverage generative modeling-based anomaly detection to enhance interpretability in AI failure detection systems and to aid data curation for large repositories. For failure detection interpretability, this retrospective study utilized 3339 CT scans (525 patients), divided patient-wise into training, baseline test, and anomaly (having failure-causing attributes—e.g., needles, ascites) test datasets. For data curation, 112,120 ChestX-ray14 radiographs were used for training and 2036 radiographs from the Medical Imaging and Data Resource Center for testing, categorized as baseline or anomalous based on attribute alignment with ChestX-ray14. StyleGAN2 networks modeled the training distributions. Test images were reconstructed with backpropagation and …

Utility Of True Cut Biopsy Tcb In Triple Diagnosis Of Breast Cancer, Ahmed Abdallah Esawy

Journal of Medicine in Scientific Research

objective : The aim of this study is to evaluate the role of breast true cut biopsy (TCB) in the diagnosis of breast Cancer and benign mimics of malignant lesions. True cut biopsy improves the classification of BI-RADS System (upgrade or downgrade, BI-RADS score).TCB decreases follow-up examinations. TCB allows definite rapid breast cancer diagnosis and management. Methods: An observational retrograde study was performed of all TCB reports of a suspicious mass or lesion observed in patients admitted between January 2022 and December 2022, at Al-Sahel Teaching Hospital Conclusion : True cut biopsy is accurate, fast method in diagnosis of breast …

Calcium Sensitizers Improve Short Term Outcome After Surgical Repair Of Pediatric Cardiac Patients With Severely Impaired Left Ventricle, Rania Aboshokka, Hanan Mohammed Hassan, Khaled S. Ahmed, Rasha Hosny, Ahmed Algebaly

Journal of Medicine in Scientific Research

Introduction: Delayed diagnosis and management of congenital cardiac defects with high LV afterload and infants with impaired coronary perfusion can lead to severe impairment of LV function. The surgical repair of these patients carries a high perioperative risk. Introduction of Inodilators in the medical management of these cases has greatly improved postoperative outcome. Aim of the work: To evaluate the effect of calcium sensitizers on short-term outcome of surgical repair of cardiac defects in pediatric cardiac patients with severely impaired left ventricle. Methods and results A retrospective study was conducted at our institute in 2024 to evaluate the effect of …

Mid-Term Results Of Tricuspid Valve Repair For Functional Tricuspid Regurgitation: Ring And Modified Band Annuloplasty, Ismail R Barrada, Ahmed S Ali, Mahmoud M Abdou

Journal of Medicine in Scientific Research

Background: The concurrent repair of functional tricuspid regurgitation (TR) is typically recommended during left-sided heart valve surgery. Several surgical techniques are available, each targeting long-term effectiveness and clinical success. Objective: This study sought to assess the mid-term outcomes of two widely used tricuspid valve repair (TVr) methods: flexible band annuloplasty (FA) and rigid ring annuloplasty (RA). Methods: This retrospective study involved 85 patients who underwent TVr along with left-sided valve surgery. Of these, 53 patients were assigned to the FA group (Group A), and 32 patients to the RA group (Group B). Transthoracic echocardiography was performed at hospital discharge and …

Early Outcomes Of Coronary Artery Bypass Grafting Versus Percutaneous Coronary Intervention For Patients With Intermediate Syntax Ii Score, Ahmed A Faragalla, Ahmed M Elshiemy, Ahmed K. Hassan, Sherif M. Elboghdady, Wael S. Nekhila

Journal of Medicine in Scientific Research

Background Navigating the treatment landscape for those whose SYNTAX II scores reside in the transitional band of 23 to 32 (the intermediate score zone) continues to present a formidable clinical dilemma, with the therapeutic arsenal offering divergent paths: the surgical undertaking of coronary artery bypass grafting (CABG), the catheter-based strategy of percutaneous coronary intervention (PCI), or the non-interventional realm of medical therapy. Aim To evaluate the frequency of major adverse cardiac or cerebrovascular events (MACCE) during the in-hospital period following re-vascularization procedures in participants graded as intermediate SYNTAX II scores. Methods A retrospective study was conducted at the National Heart …

Acute Kidney Injury After Open Heart Surgery: The Diagnostic And Predictive Value Of The New Biomarkers, Ahmed A Faragalla, Ahmed M Elshiemy, Sherif A. Elhendawy

Journal of Medicine in Scientific Research

Background Post-operative acute kidney injury (AKI) following cardiac surgery represents a significant clinical challenge, associated with heightened mortality and an increased propensity for chronic kidney disease. Ischemia-reperfusion injury, a primary pathophysiological mechanism, induces renal tubular damage, releasing biomarkers such as Neutrophil gelatinase-associated lipocalin (NGAL) and hemojuvelin (HJV) into the urine. The quantification of these urinary biomarkers offers a means for early AKI detection and risk stratification, with the potential to improve patient prognosis. Aim This investigation tested new urinary biomarkers to detect AKI within the first 24 hours, to enable prompt intervention and enhance patient care. Patients and Method Sixty-three …

Study Of Awareness, Knowledge, Attitude And Practice Of Pediatric Healthcare Practitioners Towards Wilson Disease., Hanaa Ahmed Elaraby, Magdy Anwar Saber, Sally Waheed Elkhadry, Salwa Gamal Attia, Gihan Ahmed Sobhy

Journal of Medicine in Scientific Research

Background; Wilson disease (WD) is a rare genetic disease that occurs secondary to an excess of copper building up in our body, especially in the liver and brain. Diagnosis of WD is challenging. Since it is a curable illness, raising awareness about it among medical professionals is essential. Aim of the work; to assess the awareness, knowledge, attitude and practice of pediatric practitioners towards WD providing useful alerts about this disease and augmenting their knowledge. Participants and Methods ; Five hundred and one (501) pediatric practitioners with varying academic degrees from several Egyptian governmental hospitals participated in this cross-sectional study …

Organism-Specific Sequence Motifs Link Ribosomal Rnas To Brain Disorders, Isidore Rigoutsos, Stepan Nersisyan, Eric Londin, Iliza Nazeraj, Bonnie Dong, Anastasios Vourekas, Phillipe Loher

Computational Medicine Center Faculty Papers

We report that in humans, mice, fruit flies, and worms, the ribosomal RNAs and the transcribed spacers of 45S are densely packed with organism-specific sequence motifs that are primarily shared with nervous system genes. The human ribosomal RNAs and 45S spacers contain 1,723 such motifs. Specific combinations of these motifs are predominantly found in 3,430 human nervous system genes, of which 1,046 are genes associated with brain disorders, including autism spectrum disorder and schizophrenia. The sequences of the 1,723 motifs and their locations in the introns and exons of nervous system genes are unique to primates. Experimental evidence indicates that …

A Safety-Ii Approach To Learn From Practice Variation In The Diagnostic Process In The Emergency Department: An Action Research Study, Rick Roos, Laura Zwaan, Myrthe Maranus, Iwan A Meynaar, Vanessa J Valk, Cees Van Nieuwkoop, Gert-Jan Kamps, Hardeep Singh, Maarten O Van Aken

Faculty, Staff and Students Publications

Objectives: The focus on improving patient safety has mainly been by learning from errors and near misses (Safety-I). We applied a novel Safety-II approach to identify and learn from practice variations in the diagnostic process in the emergency department (ED), and subsequently design and implement practice changes.

Methods: In this single-center study, we used action research (cycles of micro-experiments to study and improve processes with active stakeholder involvement) in the diagnostic process. We used three subsequent observation cycles of the following six steps: observations, gathering of follow-up data, analyses, a co-creation session with involved stakeholders, sharing of best practices, and …

Inhibition Of Osteosarcoma Lung Metastases By Β-Glucan And Cd40 Agonist Is Mediated By Activation Of Macrophages And Nk Cells, Pradeep Shrestha, Rejeena Shrestha, Eugenie S Kleinerman

Faculty, Staff and Student Publications

Background: Osteosarcoma (OS) lung metastases remain a significant therapeutic challenge. Innate immune activation is a promising therapeutic approach. Innate immune agonists can modulate the tumor immune microenvironment and improve therapeutic response.

Methods: Using an experimental syngeneic OS lung metastasis BALB/c mouse model with K7M3-luc OS cells, we evaluated the antitumor effects of yeast-derived particulate β-glucan in prevention and therapeutic settings. We then assessed whether the CD40 agonist (CD40a) in combination with β-glucan increased therapeutic response in two different immune-competent mouse models of OS lung tumor burden.

Results: In the pretreatment settings, mice treated with β-glucan prior to OS cell infusion …

Establishing Priority Pediatric Antimicrobial Stewardship Interventions In The Us: Findings From A Delphi Consensus Study, Harry Obeng, Emmanuel Tetteh, Sara Malone, Lauren Walsh, Tyler Walsh, Fernando J Bula-Rudas, Ritu Banerjee, Adam W Brothers, Joshua C Herigon, Katie Namtu, Scott Weissman, Daniel Riggsbee, Jared Olson, Debra Lynn Palazzi, Ann Wirtz, Matthew Sattler, Jessica Tansmore, Brittany A Rodriguez, Monica Abdelnour, Joshua R Watson, Alison C Tribble, Jessica Gillon, Mari Nakamura, Sarah Jones, Jason G Newland, Virginia R Mckay

Faculty, Staff and Students Publications

Background/objectives: Antimicrobial resistance (AMR) is a major global health threat, with children at higher risk due to developmental differences in drug metabolism, limited treatment options and inappropriate antibiotic use. Pediatric antimicrobial stewardship programs (ASPs) face implementation challenges, often relying on adult-based guidelines and limited pediatric-specific evidence. This study aimed to identify and prioritize the most critical areas for pediatric ASP intervention development through a structured, multi-round Delphi consensus process with experts in antimicrobial stewardship and infectious diseases.

Method: A four-round modified Delphi process was conducted to identify and prioritize key pediatric ASP interventions. Experts in antimicrobial stewardship and infectious diseases …

The Role Of Traumatic Brain Injury On Intimate Partner Violence And Changes In Mental Health From Late Adolescence To Young Adulthood, Eric J Connolly, Elizabeth Baumler, Deborah M Little, Meghan L Royle, Anne C Wingert, Leila Wood, Jeff R Temple

Faculty, Staff and Student Publications

Purpose: Intimate partner violence (IPV) victimization and traumatic brain injury (TBI) are common correlates of mental health problems in adolescence. However, research has yet to investigate whether IPV victimization is related to developmental changes in mental health, as well as the contributing role that TBI may play in conditioning this association. We address this gap by analyzing longitudinal data with well-validated measures of mental health from an ethnically diverse sample of adolescents.

Methods: Prospective data from the Dating it Safe sample (n = 699) were used to measure IPV victimization, depression, post-traumatic stress, binge drinking, and TBI from 2015 to …

Sers And Seira Detection Of Polycyclic Aromatic Hydrocarbons And Their Derivatives In Murine Tissues: Bioaccumulation And Clearance, Oara Neumann, Andrés B Sánchez-Alvarado, Weiwu Jiang, Guo Dong Zhou, Sachin B Jorveka, Parmeet Dhindsa, Nagireddy Putluri, Peter Nordlander, Melissa A Suter, Bhagavatula Moorthy, Naomi J Halas

Faculty, Staff and Students Publications

The toxicological effects of polycyclic aromatic hydrocarbons (PAHs) and polycyclic aromatic compounds (PACs) have attracted considerable research interest due to their known bioaccumulation. However, time-resolved and longitudinal studies that examine in vivo bioaccumulation and clearance remain limited. Here we use Surface-Enhanced Raman Scattering (SERS) and Surface-Enhanced Infrared Absorption (SEIRA) spectroscopies to detect and track the presence of two PAHs: pyrene, benzo[a]pyrene, and one PAC: 5,12-naphthacenequinone, in murine organ tissues. Mice were exposed to a three-component mixture of these three chemicals, then their organs were collected at 24-, 48-, and 72- hours post-exposure. The accumulation of each of these chemicals in …

Polychlorinated Biphenyls Alter Estrogen Receptor Β-Mediated Epigenetic Regulation, Promoting Endometriosis, Yuri Park, Nuri Sung, Eunsu Kim, Jaeyeong Jeong, Juhee Sim, Mi Jin Park, John P Lydon, Xiaoming Guan, Sang Jun Han

Faculty, Staff and Students Publications

Endometriosis is a pathological condition characterized by the ectopic growth of endometrial cells, leading to chronic pelvic pain and infertility. Epidemiological studies have associated exposure to dioxin-like polychlorinated biphenyls, particularly PCB126, with an increased risk of endometriosis. However, the underlying mechanisms of this association remain poorly understood. We utilized a surgically induced endometriosis mouse model and human endometrial cell lines to assess the impact of PCB126 on endometriosis progression. Mice were exposed to environmentally relevant doses of PCB126. Endometriotic lesion growth, estrogen receptor signaling, receptor tyrosine kinase activity, and gene expression changes induced by PCB126-mediated elevation of DNA methyltransferase 3A …

Dual Targeting Of Orphan Nuclear Receptors Nr4a1 And Nr4a2 For Nonhormonal Endometriosis Therapy, Wai Ning Tiffany Tsui, Yuri Park, Srijana Upadhyay, Da Mi Kim, Lei Zhang, Gus Wright, Amanuel Hailemariam, Arafat Rahman Oany, Sang Jun Han, Stephen Safe

Faculty, Staff and Students Publications

Previous studies show that orphan nuclear receptor 4A1 (NR4A1) regulates endometriotic cell growth, survival, estrogen receptor β (ERβ), mechanistic target of rapamycin signaling and fibrosis. NR4A2 is also expressed in epithelial and stromal derived endometriotic cells, and in this study the effects of 1,1-bis(3'-indolyl)-(3,5-disubstitutedphenyl)methane (DIM-3,5) dual NR4A1/nuclear receptor 4A2 (NR4A2) ligands and knockdown of NR4A1 and NR4A2 were investigated. The dual NR4A1/2 DIM-3,5 analogs inhibited previously identified proendometriotic pathways and gene products, and they also inhibited TWIST1 and multiple markers associated with epithelial-to-mesenchymal transition (EMT). The results show that both NR4A1 and NR4A2 regulate the same pathways, including endometriotic cell …

Germline Determinants Of Toxicity And Efficacy In Patients With Large B-Cell Lymphoma Treated With Car T-Cell Therapy, Paolo Strati, Amanda Brandt, Anath C Lionel, Jared Henderson, Jason R Westin, Sherry Adkins, Elizabeth J Shpall, Partow Kebriaei, Jeremy Ramdial, Neeraj Saini, Sairah Ahmed, Christopher Flowers, Sattva S Neelapu, Michelle A T Hildebrandt

Faculty, Staff and Student Publications

Background: Recent data have suggested that germline genetic aberrations can affect outcomes in patients with large B-cell lymphoma (LBCL) treated with chimeric antigen receptor T-cell therapy (CART). However, a comprehensive analysis of germline determinants of response and toxicity after CART has not yet been described.

Methods: Genome-wide genotyping was performed in 170 patients with LBCL treated with standard of care axicabtagene ciloleucel. Polygenic risk score instruments for blood cell traits and inflammatory markers were obtained from the PGS Catalog and analyzed using PRSice-2. Exploratory gene-based and genome-wide association study analyses were performed. Genetic ancestry of the patients with LBCL was …

Quiescent Oxphos-High Triple-Negative Breast Cancer Cells That Persist After Chemotherapy Depend On Bcl-Xl For Survival, Slawomir Andrzejewski, Marie Winter, Leandro Encarnacao Garcia, Olusiji Akinrinmade, Francisco Madeira Marques, Emmanouil Zacharioudakis, Anna Skwarska, Julio Aguirre-Ghiso, Marina Konopleva, Guangrong Zheng, Susan A Fineberg, Daohong Zhou, Evripidis Gavathiotis, Tao Wang, Eugen Dhimolea

Faculty, Staff and Student Publications

The persistent residual tumor cells that survive after chemotherapy are a major cause of treatment failure, but their survival mechanisms remain largely elusive. These cancer cells are typically characterized by a quiescent state with suppressed activity of MYC and MTOR. We observed that the MYC-suppressed persistent triple-negative breast cancer (TNBC) cells are metabolically flexible and can upregulate mitochondrial oxidative phosphorylation (OXPHOS) genes and respiratory function ("OXPHOS-high" cell state) in response to DNA-damaging anthracyclines such as doxorubicin, but not to taxanes. The elevated biomass and respiratory function of mitochondria in OXPHOS-high persistent cancer cells were associated with mitochondrial elongation and remodeling, …