Digital Commons Network^™

Esomeprazole Inhibits Proliferation Of Scleroderma Fibroblasts Via Cell Cycle Regulation, Mohammad A Khan, Shaheer Koniyan, Manisha Ahir, Anil G Jegga, Maureen D Mayes, David Gius, Justin Leung, Mark D Bonnen, Sydney B Montesi, Yohannes T Ghebre

Faculty, Staff and Student Publications

Background: Scleroderma is a complex autoimmune disease characterized by abnormal fibroblast proliferation and excessive collagen deposits in the skin and internal organs. We previously showed that esomeprazole, an FDA-approved drug for gastric disorders, may prevent dermal fibrosis.

Methods: To test this, we evaluated the antiproliferative effect of esomeprazole and the underlying molecular mechanisms using primary fibroblasts derived from patients with scleroderma. BrdU incorporation, flow cytometry, immunofluorescence, Western blot analysis, RNA sequencing, and functional enrichment analysis were performed.

Results: Esomeprazole inhibited the proliferation of scleroderma fibroblasts in a dose-dependent manner, as measured by BrdU incorporation and Ki-67 marker. Intriguingly, esomeprazole arrested …

Oral Microbiome Brain Axis And Cognitive Performance In Older Adults, Darbaz Adnan, Phillip A Engen, Michelle Villanueva, Shohreh Raeisi, Vivian Ramirez, Ankur Naqib, Stefan J Green, Faraz Bishehsari, Lisa L Barnes, Ali Keshavarzian, Klodian Dhana, Robin M Voigt

Faculty, Staff and Student Publications

The human oral microbiota is a community of microorganisms that reside in the oral cavity, including lingual, buccal, and saliva, each niche with a distinct microbial composition. Alterations in oral microbiota have been associated with an increased risk of Alzheimer’s disease (AD). This study used data from 143 older adults in the MIND trial to evaluate the association between oral microbiome and cognitive function. Oral niche-specific differences (saliva, buccal, and lingual), as well as the microbiome composition differences (α and β diversity), were associated with cognitive function. A lower abundance of Gemella and a higher abundance of anaerobic pro-inflammatory bacteria …

Decline In Attrition Rates In United States Pediatric Residency And Fellowship Programs, 2007–2020: A Repeated Cross-Sectional Study, Emma Omoruyi, Greg Russell, Kimberly Montez

Faculty, Staff and Student Publications

Purpose: Declining fill rates in US pediatric residency and subspecialty programs requires trainee retention. Attrition, defined as transfers, withdrawals, dismissals, unsuccessful completions, or deaths, disrupts program function and impacts the pediatric workforce pipeline. It aims to evaluate attrition trends among pediatric residents and fellows in Accreditation Council for Graduate Medical Education (ACGME)-accredited programs from 2007 to 2020.

Methods: This repeated cross-sectional study analyzed publicly available ACGME Data Resource Book records. Attrition rates and 95% confidence intervals (CIs) were calculated overall and by subspecialty. Logistic regression assessed temporal changes; odds ratios (ORs) compared 2020 to 2007.

Results: From 2007-2020, pediatric residents …

Case Report: Coronary Vasospasm Precipitating Stemi And Polymorphic Ventricular Tachycardia-A Case Of Cardiotoxicity From 5-Fu Based Chemotherapy In A 41-Year-Old Woman, Ammar Hasnie, Zachary Neace, Kristin Ellison, Aaron Hesselson, Karam Ayoub, Mohammed Al-Yafi, Amit Arbune

Faculty, Staff and Student Publications

Background: Intravenous 5-fluorouracil (5-FU), in combination with oxaliplatin and folinic acid, makes up a chemotherapy regimen commonly referred to as FOLFOX. It is well-established for its efficacy in patients with advanced colorectal cancer; however, the benefits are accompanied by potential side effects that warrant careful consideration. Common toxicities can range from nausea and vomiting to neuropathy. Cardiotoxicities related to FOLFOX and fluoropyrimidines in general are extremely rare but can easily be fatal.

Case presentation: A 41-year-old woman who was recently diagnosed with stage IIIc colorectal cancer after she underwent a subtotal colectomy was admitted to the Oncology clinic for further …

Rho/Rock Pathway As A Therapeutic Target In Multiple Diseases, Zixiu Cheng, Shannon Erhardt, Jun Wang

Faculty, Staff and Student Publications

The Rho/ROCK (Rho-associated coiled-coil-containing protein kinase) signaling pathway plays a pivotal role in regulating diverse cellular processes, including cytoskeletal organization, cell migration, proliferation, and apoptosis. Dysregulation of this pathway has been implicated in the pathogenesis of various diseases, such as cardiovascular disorders, cancer, neurological conditions, and fibrotic diseases. Accumulating evidence supports the therapeutic potential of targeting Rho/ROCK, with several inhibitors currently under investigation or in clinical use. This review summarizes the molecular mechanisms underlying Rho/ROCK signaling, explores its involvement in disease progression, and discusses recent advances in the development of and the clinical application of ROCK inhibitors as promising therapeutic …

Revisiting Cytomegalovirus In Pediatric Allogeneic Hematopoietic Stem Cell Transplant Recipients: Current Strategies For Prevention And Management In The Letermovir Era, Lisa Hiskey, Diego R Hijano, Ramia Zakhour

Faculty, Staff and Student Publications

CMV infection remains the most common clinically significant infection in pediatric allogeneic hematopoietic stem cell (HCT) recipients, with seropositive recipients of transplants from seronegative donors at the highest risk for complications. In recent years, letermovir, a novel antiviral with a favorable toxicity profile, was approved first for adults and more recently for pediatric patients for the primary prophylaxis of CMV infection and disease in high-risk HCT recipients. Growing evidence from real-life data regarding the safety and efficacy of letermovir has transformed the landscape of CMV disease in HCT transplant recipients and led to a paradigm shift from a preemptive approach …

Safety Of Indocyanine Green Microdosing For Clinical Imaging Of Csf Ventricular Dynamics And Extracranial Outflow, Miriam Zamorano, Banghe Zhu, Ahmed T Massoud, Jonathan Hendricks, H Alex Choi, Pedram Peesh, Brandon A Miller, Xinhai Robert Zhang, Manish N Shah, Eva M Sevick-Muraca

Faculty, Staff and Student Publications

Background and purpose: Intravenous administration of indocyanine green (ICG) has been approved in brain surgeries for decades, yet concerns about neurotoxicity prevent its direct administration into the cerebrospinal fluid (CSF). Armed with prior animal studies demonstrating the feasibility of using ICG microdosing into the CSF, we sought to evaluate its nonclinical safety profile and obtain surrogate measures in adults prior to its use in human neonates.

Methods: Evaluation of ICG toxicity was conducted in mixed primary CNS cell cultures and in an extended safety study of juvenile rat pups deploying intraventricular injections of saline (as control) or ICG. Analysis of …

Molecular, Histologic, And Clinical Characterization Of Methylation Class Pleomorphic Xanthoastrocytoma: An Analysis Of 469 Tumors, Christopher H Dampier, Niharika Shah, Kristyn Galbraith, Azadeh Ebrahimi, Osorio Lopes Abath Neto, Zied Abdullaev, Sanda Alexandrescu, Felipe Andreiuolo, Terri Armstrong, Tiffany Baker, Sahara Cathcart, Hye-Jung Chung, Patrick J Cimino, Kyle S Conway, Jennifer Cotter, Felipe D'Almeida Costa, Karen Dazelle, Nima Etminam, Sima Esther Ferman, Igor Fernandes, Christina K Ferrone, Ahmed Gilani, Mark Gilbert, Jason Gregory, Courtney Ketchum, Han Sung Lee, Ina Lee, Maria Beatriz S Lopes, Qinwen Mao, Michael S Marshall, Matthew Mccord, Stewart G Neill, Jeffrey J Nirschl, Byram H Ozer, Werner Paulus, Marta Penas-Prado, Marco Prinz, Peter Pytel, Martha Quezado, Mark Raffeld, Sharika Rajan, Miriam Ratliff, Guido Reifenberger, Lorraina Robinson, Jens Schittenhelm, Daniel Schrimpf, Omkar Singh, Christian Thomas, Diana Thomas, Jaiyeola Thomas-Ogunniyi, Angus Toland, Rust Turakulov, Rachael Vaubel, Nitin Wadhwani, Jing Wu, Caterina Giannini, Matija Snuderl, Sebastian Brandner, Andreas Von Deimling, Kenneth Aldape

Faculty, Staff and Student Publications

Background: Methylation class pleomorphic xanthoastrocytoma (mcPXA) comprises tumors with the DNA methylation signature of classical PXA but with a wider histologic spectrum, including overlap with glioblastoma (GBM).

Methods: To clarify the histologic and molecular scope of mcPXA and characterize its clinical behavior, a cohort of 469 tumor samples from 458 patients matching to mcPXA by the DKFZ classifier (v12.6 score ≥0.85) was interrogated.

Results: Patient median age was 23 years (range 1-73 years) with a female predominance (259 female/199 male). CDKN2A/B homozygous deletion was observed in 406 of 469 (87%) samples. In samples tested for BRAF p.V600E mutations (n …

Reducing Computed Tomography Use For Appendicitis Evaluation In A Pediatric Emergency Department: A Multidisciplinary Quality Improvement Initiative, Jennifer Hockenbury, Monica E Lopez, Caroline M Godfrey, Martin L Blakely, Melissa Danko, Marta Hernanz-Schulman, S Barron Frazier

Faculty, Staff and Student Publications

Introduction: Appendicitis is the most common pediatric surgical emergency, and computed tomography (CT) remains an overused diagnostic test for appendicitis. Our institutional rate of CT utilization for suspected appendicitis was higher than in peer children's hospitals, so we aimed to reduce CT utilization during the evaluation of pediatric appendicitis from 31.3% to 15% within 12 months.

Methods: From September 2021 to October 2022, we conducted a multidisciplinary quality improvement initiative among patients evaluated for appendicitis in the pediatric emergency department (PED). Interventions included standardizing evaluation with a clinical practice guideline, an order set in the electronic medical record for clinical …

Moving From Prognostication To Prevention Of Ssis In Lmics, Stephanie Martinez Ugarte, Mokunfayo O Fajemisin, Lillian S Kao

Faculty, Staff and Student Publications

No abstract provided.

Topss: Tolerability Of Transcranial Direct Current Stimulation In Pediatric Stroke Survivors, Stuart Fraser, Anna Clearman, Melika Abrahams, Bernadette Gillick, Tia Lal, Sean Savitz, Nuray Yozbatiran

Faculty, Staff and Student Publications

Background: Transcranial direct current stimulation is a non-invasive neuromodulation technique with emerging therapeutic potential in neurodevelopmental conditions. While childhood-onset stroke survivors frequently experience long-term motor impairment, there are very few studies examining the safety and feasibility of transcranial direct current stimulation in this population.

Objective: To evaluate the safety, feasibility, and tolerability of bihemispheric transcranial direct current stimulation paired with occupational therapy in children and adolescents with chronic hemiparesis following childhood-onset arterial ischemic stroke or intracranial hemorrhage.

Methods: In this single-arm, open-label pilot study, five participants aged 6-19 years of age received five daily sessions of transcranial direct current stimulation …

Palliative Care In Acute Care Surgery: Research Challenges And Opportunities, Amelia W Maiga, Vanessa Ho, Rachel S Morris, Lisa M Kodadek, Thaddeus J Puzio, Gail T Tominaga, Masami Tabata-Kelly, Zara Cooper

Faculty, Staff and Student Publications

Palliative care includes effective communication, relief of suffering and symptom management with an underlying goal of improving the quality of life for patients with serious illness and their families. Best practice palliative care is delivered in parallel with life-sustaining or life-prolonging care. Palliative care affirms life and regards death as a normal process, intends neither to hasten death nor to postpone death and includes but is not limited to end-of-life care. Palliative care encompasses both primary palliative care (which can and should be incorporated into the practice of acute care surgery) and specialty palliative care (consultation with a fellowship-trained palliative …

Latent Classes Of Adolescent Trauma Exposure, Posttraumatic Stress Disorder Symptoms, And Substance Use Predict Clinical Diagnoses At 12-Month Follow-Up, John Leri, Josh M Cisler, Shaunna L Clark, Cody G Dodd, Saman Siddiqui, Leslie Taylor, Alexa Ayala, Sunita Stewart, Robyn Richmond, Jeffrey D Shahidullah, Justin F Rousseau, John M Hettema, D Jeffrey Newport, Karen D Wagner, Charles B Nemeroff

Faculty, Staff and Student Publications

BACKGROUND: Trauma exposure, posttraumatic stress disorder (PTSD), and substance use commonly co-occur among youth. Identifying specific subgroups of youth based on unique constellations across these domains may provide a novel way to identify and target youth at prospective risk for specific types of negative clinical outcomes.

METHODS: Trauma exposed youth completed structured clinical assessments as part of a longitudinal study (

RESULTS: Four latent classes were identified which differentiated participants based on the type of trauma exposure, the number of PTSD symptoms endorsed, and the propensity to be engaged in polysubstance use. Latent classes which were characterized by exposure to …

The Urgent Need For Well-Being Programs In Medical Residencies In Brazil, Marcelo Bruno Generoso, Pedro Shiozawa, Ricardo Uchida, Marsal Sanches

Faculty, Staff and Student Publications

No abstract provided.

Brazilian Psychiatric Association Guidelines For The Treatment Of Social Anxiety Disorder, Leonardo Baldaçara, Thales Marcon Almeida, Diogo Cesar Dos Santos, Ana Beatriz Paschoal, Aldo Felipe Pinto, Luiz Antonio Vesco Gaiotto, Diogo De Lacerda Veiga, Fabiano Franca Loureiro, Leandro Fernandes Malloy-Diniz, Roseli Lage De Oliveira, Quirino Cordeiro, Marsal Sanches, Antônio E Nardi, Antônio Geraldo Da Silva, Ricardo R Uchida

Faculty, Staff and Student Publications

Social anxiety disorder (SAD), one of the most prevalent anxiety disorders, is not well recognized. In most cases, SAD follows an unremitted and chronic course, affecting individual functioning in relationships, education, and work. Due to the disorder’s relevance in Brazil, guideline-based treatments adapted to the Brazilian social and economic context are needed. We conducted a systematic review assessing several treatment modalities for SAD. PubMed, Cochrane, SciELO, and ClinicalTrials.gov were searched using the Medical Subject Headings social anxiety disorder and social phobia. Of the 438 selected articles, 20 were selected. Selective serotonin reuptake inhibitors are considered a first-line treatment for SAD …

Examining The Relationship Between Cardiometabolic Risk Factors And Telomere Length In Women: A Systematic Review, Jeni Page, Catherine Stephens, Melissa A Richard, Elizabeth Lyons, Elizabeth Baumler, M Terese Verklan, Elizabeth Lorenzo

Faculty, Staff and Student Publications

Background and objectives: Cardiometabolic syndrome (CMS) poses a significant public health challenge due to its rising prevalence in aging and significant healthcare costs. Recent studies have suggested telomere length (TL), a marker of cellular aging, may be impacted by CMS among women, but comprehensive evidence remains limited. This study aimed to examine the association between CMS risk factors (increased waist circumference [WC], elevated blood pressure, impaired fasting blood glucose, elevated triglycerides, decreased high-density lipoproteins) and TL in women, with consideration of age and race or ethnicity.

Research design and methods: A systematic review was conducted following PRISMA guidelines, with searches …

Detection Of Erg11 Gene Mutation In Coding And Non-Coding Regions Of Clinical Candida Glabrata (Nakaseomyces Glabratus) Isolates From Pakistan, Saba Memon, Najia Karim Ghanchi, Urooj Zafar, Joveria Farooqi, Sadaf Zaka, Kauser Jabeen

Faculty, Staff and Student Publications

Azoles inhibit the cytochrome P450-dependent enzyme lanosterol 14α-demethylase (CYP51) that is encoded by the ERG11 gene. Azole resistance in Candida species arises through different mechanisms, like mutations in the ERG11 gene, ERG11 overexpression, CDR1,2 (Candida drug resistance) overexpression that actively efflux azole drugs, reducing their intracellular concentration and therapeutic effectiveness, and biofilm formation. We sequenced the ERG11 gene to determine mutations in the coding and non-coding regions of ERG11 in clinical isolates of Candida glabrata (Nakaseomyces glabratus) from Pakistan. Eight C. glabrata (N. glabratus) strains from our fungal strain bank (five fluconazole-resistant and …

Peer Support During In Vivo Exposure Homework Increases Likelihood Of Prolonged Exposure Therapy Completion, Melba A Hernandez-Tejada, Madeline J Bruce, Wendy Muzzy, Anna Birks, Giovanni Macedo E Cordeiro, Stephanie M Hart, Stephanie Hamski, Ron Acierno

Faculty, Staff and Student Publications

Exposure-based treatments such as prolonged exposure therapy (PE) are effective for veterans with PTSD. However, dropout rates as high as 50% are common. The Department of Veterans Affairs employs peers to increase mental health treatment engagement, however peers are not routinely used to help patients complete PE homework assignments. The present study included 109 veterans who decided to drop out from exposure-based treatment after completing seven or fewer sessions and used a randomized controlled design to compare PE treatment completion rates in response to 2 forms of peer support: (1) standard weekly telephone-based peer support vs. (2) peer-assisted in vivo …

Therapeutic Alliance In A Culturally Tailored Transition Program For Latino Young Adults With Autism And Their Families, Antonio F Pagán, Katherine A Loveland, Ron Acierno

Faculty, Staff and Student Publications

Latino young adults with autism spectrum disorder (ASD) often face barriers to accessing culturally appropriate interventions that support adaptive functioning and family dynamics. Therapeutic alliance, the collaborative and trusting relationship between participants and providers, is a critical component of intervention success, yet its role in culturally tailored programs for Latino families remains underexplored. The present study examined therapeutic alliance in ¡Iniciando! la Adultez, a 12-week, culturally adapted intervention for Latino young adults with ASD and their Spanish-speaking parents. The program integrates Latino cultural values and language and consists of parent group therapy, young adult group therapy, and individual therapy sessions. …

Inducing Hypertension In Myh11r247c/R247c Mice Triggers Aortic Dissections With Increased Focal Adhesion Kinase Signaling, Callie S Kwartler, Shanzhi Wang, Zhen Zhou, Pujun Guan, Yang Yu, Xue-Yan Duan, Theodore Zhang, Jiyuan Chen, Elaine C Davis, Dianna M Milewicz

Faculty, Staff and Student Publications

Objective: We sought to determine if hypertension in combination with a "variant of uncertain significance" that disrupts protein function, MYH11 p.Arg247Cys, would induce aortic dissections in a mouse model.

Approach and results: Administration of L-NAME via drinking water and a high salt diet increased blood pressure in WT and Myh11R247C/R247C mice and triggered type A dissections with cardiac tamponade in 20% of the Myh11R247C/R247C mice. Myh11R247C/R247C aortas have aberrant smooth muscle contractile unit-elastin connections by transmission electron microscopy, along with increased focal adhesion signaling at baseline, which further increases with hypertension.

Conclusion: Gene-environment interactions trigger aortic dissections in Myh11R247C/R247C mice.

Exploring The Role Of Reward Functioning In The Overlap Of Post-Traumatic Stress And Cocaine Use Disorder, Kate Hull, Hanaan Bing-Canar, Krista Miloslavich, Christopher Holden, Aneet Ahluwalia, Scott D Lane, Joy M Schmitz, Margaret C Wardle

Faculty, Staff and Student Publications

Background: Posttraumatic stress disorder (PTSD) symptoms are common in people with cocaine use disorder (CUD), and even sub-threshold PSTD symptoms result in worse treatment outcomes. Difficulties with reward functioning may drive this comorbidity. Impairments in reward functioning are prominent in both PTSD and CUD and contribute to development of substance use problems after trauma. There are three distinct reward processes that may be involved in the PTSD/CUD overlap: consummatory reward (ability to experience pleasure), motivational reward (willingness to exert effort for rewards), and reward learning (adapting behavior based on reward history). Here we test whether impairments in these reward functions …

Hepatic Metabolic Signature And Its Association With The Response To Immunotherapy In Hepatocellular Carcinoma, Hyewon Park, Sowon Park, Kena Park, Sun Young Yim, Ju-Seog Lee, Sung Hwan Lee

Faculty, Staff and Student Publications

Introduction: Increased metabolic activity is frequently observed in hepatocellular carcinoma (HCC). However, the impact of this increased metabolic activity on the efficacy of current treatments, such as the combination immunotherapy using atezolizumab and bevacizumab for HCC, remains unknown.

Methods: Gene expression data from mouse livers representing hepatic metabolic activity and HCC patient tumor tissues were used to identify a transcriptomic signature for high metabolic activity in HCC tumors. The hepatic metabolic signature (HMS) was used to categorize HCC patients treated with atezolizumab plus bevacizumab or sorafenib from the IMbrave150 clinical trial into high-or low-metabolic groups, using multiple statistical approaches to …

Immune Responses In Rodent Whole Eye Transplantation: Elucidation And Preliminary Investigations Into Rejection Diagnosis And Monitoring, Bing Li, Yong Wang, Charles R Owens, Touka Banaee, Charleen T Chu, Kayvon Jabbari, Anna D Lee, Neil J Khatter, Alan G Palestine, An-Jey A Su, Christene A Huang, Kia M Washington

Faculty, Staff and Student Publications

Background: Whole Eye Transplantation (WET) offers potential for vision restoration but is hindered by the complex challenge of immune rejection. Understanding and closely monitoring these immunological responses is crucial for advancing WET. This study delves into the timeline and nature of immune responses in a rodent model of WET without immunosuppression, aiming to elucidate a detailed picture of the immune landscape post-transplantation and establish innovative diagnostic and monitoring methods.

Methods: We employed a multi-faceted approach to analyze immune responses post-WET, including assessments of gross changes in corneal transparency, thickness, and skin condition. Histopathological examinations of both ocular and surrounding skin …

Dosimetric Evaluations Using Cycle-Consistent Generative Adversarial Network Synthetic Ct For Mr-Guided Adaptive Radiation Therapy, Gabriel L Asher, Shiru Wang, Bassem I Zaki, Gregory A Russo, Gobind S Gill, Charles R Thomas, Temiloluwa O Prioleau, Yuting Li, Rongxiao Zhang, Yue Yan, Brady Hunt

Faculty, Staff and Student Publications

Background: Magnetic resonance (MR) guided radiation therapy combines high-resolution image capabilities of MRI with the precise targeting of radiation therapy. However, MRI does not provide the essential electron density information for accurate dose calculation, which limit the application of MRI. In this presented work, we evaluated the potential for Deep Learning (DL) based synthetic CT (sCT) generation using 3D MRI setup scans acquired during real-time adaptive MRI-guided radiation therapy.

Methods: We trained and evaluated a Cycle-consistent Generative Adversarial Network (Cycle-GAN) using paired MRI and deformably registered CT scan slices (dCT) in the context of real-time adaptive MRI-guided radiation therapy. Synthetic …

A Phase Ib/Ii Trial Of Neoadjuvant Neratinib Added To Standard Therapy In Patients With Her2-Positive Or Hr-Positive/Her2-Negative Inflammatory Breast Cancer (Including Stage Iii And Iv Disease), Bora Lim, Angela Marx, Megumi Kai, Angela Alexander, Roland Bassett, Wencai Ma, Jie Willey, Huiming Sun, Azadeh Nasrazadani, Mohammad M Mohammad, Jianhua Zhang, Anthony Lucci, Susie X Sun, Michael C Stauder, Gary J Whitman, Huong Le-Petross, Vicente Valero, Wendy A Woodward, Rachel M Layman

Faculty, Staff and Student Publications

Background: Inflammatory breast cancer (IBC) is rare but aggressive, characterized by the rapid onset of diffuse skin erythema, edema, tenderness, induration, and fast metastasis. Both hormone receptor positive (HR+) and human epidermal receptor 2 positive (HER2+) are associated with inferior response after neoadjuvant systemic therapy (NAST) compared to non-IBC. Despite multimodal treatment approaches, the 3-year overall survival rate for stage III IBC remains low at approximately 74%, around 10% lower than the 83% for non-IBC.

Objectives: To evaluate whether the addition of neratinib, an irreversible pan-ErbB receptor small molecule tyrosine kinase inhibitor, improves the rate of pathological complete response in …

Case Report: Successful Delivery Following Chemotherapy In A Pregnant Patient With Metastatic Smarcb1-Deficient Renal Medullary Carcinoma, Panayiotis D Kontoyiannis, Adam Kuykendal, Chad Tang, Jessica P Cheng, Beei Chan, Susan S Thomas, Priya Rao, Bora Lim, Pavlos Msaouel

Faculty, Staff and Student Publications

SMARCB1-deficient renal medullary carcinoma (RMC) is a rare and aggressive kidney cancer defined by the loss of SMARCB1 tumor suppressor and primarily affecting adolescents and young adults with sickle hemoglobinopathies. Approximately 7% of RMC cases, known as renal cell carcinoma unclassified with medullary phenotype (RCCU-MP), lack sickle hemoglobinopathy. RMC does not respond to immune checkpoint inhibitors and antiangiogenic tyrosine kinase inhibitors, with chemotherapy being the main treatment. Here we present the first documented case of RMC diagnosed during pregnancy. A 24-year-old woman presented with right-sided back pain, leading to the discovery of a 6-cm right renal mass. Pathology confirmed RCCU-MP …

Comb-Boin12: A Utility-Based Bayesian Optimal Interval Design For Dose Optimization In Cancer Drug-Combination Trials, Mengyi Lu, Jingyi Zhang, Ying Yuan, Ruitao Lin

Faculty, Staff and Student Publications

Drug combinations are increasingly utilized in cancer treatment to enhance drug effectiveness through synergistic therapeutic effects. However, determining the optimal biological dose combination (OBDC) in small-scale drug combination trials presents challenges due to the increased complexity of the dose space. To effectively optimize the dose combination of combined drugs, we propose a model-assisted design by extending the single-agent Bayesian optimal interval phase I/II (BOIN12) design. Our approach incorporates a utility function to balance the trade-off between risk and benefit and directly models the utility of each dose by constructing a quasi-beta-binomial model. A key advantage of our design is the …

Consolidation Alk Tyrosine Kinase Inhibitors Versus Durvalumab Or Observation After Chemoradiation In Unresectable Stage Iii Alk-Positive Nsclc, Amin H Nassar, Ritujith Jayakrishnan, Jamie Feng, Frances Shepherd, Elio Adib, Justin M Cheung, Jessica J Lin, Yufei Liu, Steven H Lin, Kaushal Parikh, Arthi Sridhar, Purnima Shakya, Thomas J Dilling, David Kaldas, Jhanelle E Gray, Anastasiya Lobachov, Jair Bar, Heike Luders, Christian Grohe, Shruti Gupta, Ticiana Leal, Bailey Fitzgerald, Fionnuala Crowley, Yu Fujiwara, Thomas U Marron, Molly Wilgucki, Joshua Reuss, Luxi Chen, Kamya Sankar, Jacqueline V Aredo, Joel W Neal, Heather A Wakelee, Rohit Thummalapalli, Helena Yu, Ryan Whitaker, Ana Velazquez, Meera Ragavan, Alessio Cortellini, David J Kwiatkowski, Abdul Rafeh Naqash, Sarah B Goldberg, So Yeon Kim

Faculty, Staff and Student Publications

Introduction: Patients with advanced ALK-positive NSCLC typically have poor response to immunotherapy; the benefit of consolidation durvalumab in patients with unresectable stage III ALK-positive NSCLC remains unclear. Herein, we compare the efficacy and safety of consolidation ALK tyrosine kinase inhibitor (TKI) versus durvalumab or observation after concurrent chemoradiation.

Methods: We conducted a retrospective study using a multicenter study of 17 institutions globally. Patients with unresectable stage III ALK-positive NSCLC treated between 2015 and 2022 were included. Patients received ALK TKI, durvalumab, or observation after concurrent chemoradiation. Real-world progression-free survival (rwPFS) and overall survival (OS) were estimated using Kaplan-Meier method. Treatment-related …

Stim1 And Lipid Interactions At Er-Pm Contact Sites, Yuepeng Ke, Ritchel Gannaban, Junchen Liu, Yubin Zhou

Faculty, Staff and Student Publications

Store-operated calcium (Ca2+) entry (SOCE) represents a major route of Ca2+ permeation across the plasma membrane (PM) in non-excitable cells, which plays an indispensable role in maintaining intracellular Ca2+ homeostasis. This process is orchestrated through the dynamic coupling between the endoplasmic reticulum (ER)-localized Ca2+ sensor stromal interaction molecule 1 (STIM1) and the PM-resident ORAI1 channel. Upon depletion of ER Ca2+ stores, STIM1 undergoes conformational rearrangements and oligomerization, leading to translocation of STIM1-containing ER membrane towards the PM. This movement is facilitated by the physical interaction between positively charged cytosolic domains within STIM1 and negatively charged phospholipids embedded in the PM, …

Combining Biology-Based And Mri Data-Driven Modeling To Predict Response To Neoadjuvant Chemotherapy In Patients With Triple-Negative Breast Cancer, Casey E Stowers, Chengyue Wu, Zhan Xu, Sidharth Kumar, Clinton Yam, Jong Bum Son, Jingfei Ma, Jonathan I Tamir, Gaiane M Rauch, Thomas E Yankeelov

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with limited targeted treatment options, heterogeneous treatment response, and high risk of early recurrence. Artificial intelligence (AI) has rapidly emerged as a powerful tool to address key clinical challenges in TNBC across diagnosis, treatment response assessment, and prognosis. Diagnostic and staging challenges persist due to variable imaging features in TNBC and limitations in conventional modalities, increasing the risk of delayed detection. Predicting response to neoadjuvant systemic therapy remains difficult, as patient responses are heterogeneous, and existing clinical markers provide limited early predictive value. Prognostication in TNBC is similarly constrained …