Genetic Phenomena Commons^™

Partial Cystectomy For Muscle-Invasive Bladder Cancer, Peter S Palencia, Nethusan Sivanesan, Syed Rahman, Fady Ghali, David Hesse, John Colberg, Ashwin Sridhar, John D Kelly, Byron H Lee, Ashish M Kamat, Wei-Shen Tan

Faculty, Staff and Student Publications

Partial cystectomy is a surgical bladder-sparing option for selected patients with muscle-invasive bladder cancer (MIBC), urachal adenocarcinoma and diverticular bladder tumors. Partial cystectomy hold several advantages. It allows for definite pathology and accurate staging while avoiding side effects from radiation therapy and preserves the option for salvage radical therapy (radical cystectomy or radical radiotherapy). Patients should have a CT urogram, prostatic urethral biopsy and mapping biopsies or blue light cystoscopy to rule out multifocal disease or CIS. Small solitary MIBC patients without carcinoma in situ in an area of the bladder where resection can be performed with negative margin would …

Bcl-2/Bcl-Xl Dual Inhibition Triggers Gasdermin D-Mediated Pyroptosis In Mantle Cell Lymphoma, Yijing Li, Joseph Mcintosh, Vivian Jiang, Fangfang Yan, Jovanny Vargas, Yuxuan Che, Wei Wang, Ching-Fei Li, Yue Fei, Celeste Lee, Lei Nie, Yixin Yao, Michael Wang, Heng-Huan Lee, Yang Liu

Faculty, Staff and Student Publications

No abstract provided.

Rna Sequencing And Immunohistochemistry Jointly Improve Tumor Biomarker Interpretation, Vladimir Kushnarev, Danil Stupichev, Suren Davitavyan, Kirill Kriukov, Basavaraja U Shanthappa, Anna Butusova, Sofia Menshikova, Anna Belozerova, Anastasia Shvyrkova, Arina Tkachuk, Olga Khatenkova, Linda Balabanian, Ekaterina Postovalova, Jochen K Lennerz, Funda Meric-Bernstam, Alexander Bagaev

Faculty, Staff and Student Publications

This study aimed to assess the correlation between RNA sequencing (RNA-seq) and immunohistochemistry (IHC) in detecting key cancer biomarkers across solid tumors, and then, to establish RNA-seq thresholds that accurately reflect clinical IHC classifications. Expression levels of nine biomarkers-ESR1, PGR, AR, MKI67, ERBB2, CD274, CDX2, KRT7, and KRT20-were analyzed in 365 formalin-fixed, paraffin-embedded samples from breast, lung, gastrointestinal, and other solid carcinomas. Correlations between RNA-seq data and IHC scores were determined using Spearman's correlation coefficients, with RNA-seq cut-offs established to distinguish positive from negative IHC scores. The results revealed strong correlations for most biomarkers, with coefficients ranging from 0.53 to …

Bridging Psychiatry And Rare Genetic Diseases: A Scoping Review Of Therapeutic Strategies And Diagnostic Delay Paired With Healthcare Economic Burden Analysis, Sheldon R Garrison, Isaac J Siegel, Christopher R Takala, Sarah L Vaithilingam, Gene W Yang, Anthony W Zoghbi, Madeline M Hartig, Sreya Vadapalli, Margaret E Anderson

Duncan NRI Faculty and Staff Publications

Rare genetic diseases (RDs) with primary neuropsychiatric symptoms pose unique challenges for diagnosis and management. While the majority of these RDs have neuropsychiatric symptoms that are secondary to the RD, a subset presents with primary neuropsychiatric symptoms directly linked to their underlying pathophysiology. This subset has significant unmet medical need with delayed diagnoses leading to prolonged delays in treatment optimization and the trialing of medications that fail to target the underlying pathophysiology. This comprehensive review identifies 108 RDs with central neuropsychiatric symptoms that have a 7.7-year average diagnostic delay. Optimal management strategies for these RDs typically includes non-psychotropic medications, dietary …

Rapid Dissection And Dissociation Of The Mouse Olfactory Epithelium For Single-Nucleus Suspensions, Benjamin D W Belfort, Anthony M Insalaco, Claude C Chew, Johnathan D Jia, Julia Younis, Benjamin R Arenkiel

Duncan NRI Faculty and Staff Publications

The murine olfactory epithelium is the initial entry point of the olfactory system, housing various cell types that include olfactory sensory neurons, their regenerating progenitors, and support cells. Olfactory sensory neurons transduce chemical odorants into neural signals, yet the mechanisms underlying how these cells develop and turnover, create synapses with the olfactory bulb, and regulate their odorant receptors remain areas of intense study. Located on the dorsal aspect of the nasal cavity, the olfactory epithelium adheres to intricate bony structures known as turbinates. This anatomy poses unique challenges for its extraction and dissociation, especially in the context of preparing viable …

De Novo And Inherited Variants In Ddx39b Cause A Novel Neurodevelopmental Syndrome, Kevin T A Booth, Sharayu V Jangam, Martin M C Chui, Kayla Treat, Lorenzo Graziani, Alessia Soldano, Yao Ruan, Jeffrey Wan-Hei Hui, Kerry White, Celanie K Christensen, Ty Lynnes, Shinya Yamamoto, Oguz Kanca, Mandy H Y Tsang, Sally A Lynch, Sureni V Mullegama, Julia Baptista, Daniela Iancu, Shelagh K Joss, Sandra Y Y Wong, Christopher C Y Mak, Anna K Y Kwong, Hugo J Bellen, Erin Conboy, Remo Sanges, Anskar Yu-Hung Leung, Michael F Wangler, Brian H Y Chung, Francesco Vetrini

Duncan NRI Faculty and Staff Publications

DDX39B is a conserved member of the DEAD-box family of ATP-dependent RNA helicases, critical in mRNA metabolism across eukaryotes. DDX39B is also a core component of the TRanscription-EXport (TREX) super protein complex, and recent studies have highlighted the important role of its subunits in neurodevelopmental disorders. Here, we describe six individuals from five families, four harbouring de novo missense variants in DDX39B and one with an inherited splicing variant, presenting with variable developmental delay, congenital hypotonia, epilepsy, short stature, skeletal abnormalities, dysmorphic features and microcephaly in three patients.

3D molecular modelling predicts these variants would alter protein structure. In vitro …

Folliculin Depletion Results In Liver Cell Damage And Cholangiocarcinoma Through Mit/Tfe Activation, Bruno Maria Custode, Francesco Annunziata, Felipe Dos Santos Matos, Valentina Schiano, Veronica Maffia, Milena Lillo, Rita Colonna, Rossella De Cegli, Andrea Ballabio, Nunzia Pastore

Duncan NRI Faculty and Staff Publications

Mutations in the tumor suppressor gene Folliculin (FLCN) are responsible for Birt-Hogg-Dube’ (BHD) syndrome, a rare inherited condition that predisposes affected individuals to skin tumors, pulmonary cysts, and kidney tumors. FLCN regulates key cellular pathways, including TFEB, TFE3, and mTORC1, which are critical for maintaining cell homeostasis. Loss of FLCN leads to both hyperactivation of mTORC1 and constitutive activation of TFEB and TFE3, contributing to tumorigenesis. While previous studies showed that Flcn liver-specific conditional knockout (FlcnLiKO) mice are protected from developing liver fibrosis and damage upon high-fat diet exposure, the potential role of FLCN loss in liver carcinogenesis …

Isolation And Functional Properties Of Highly-Purified N-Terminal Domain Of Human Napi2b By Scalable “Resin Overload” Technique, Daria Savenkova, Irina Makarenko, Daria Nedorezova, Ramziya Kiyamova, Mikhail Bogdanov

Faculty, Staff and Student Publications

Despite the enthusiasm and advances in the purification of native and engineered full-length membrane proteins, little attention has been paid to their fragments which could serve as attractive inspiration for function, regulation, or targeting of full-length membrane protein with therapeutic antibodies (Abs). Production of recombinant fragments of "therapeutic" membrane proteins for early-stage discovery research requires their purification to near homogeneity. It is important not only for the production of biotherapeutic antibodies but also for structural and functional studies of competitive protein-Abs, protein-protein, and lipid-protein interactions which heavily rely on the purity and quality of the isolated protein fragment of interest. …

2025 European Leukemianet Recommendations For The Management Of Chronic Myeloid Leukemia, Jane F Apperley, Dragana Milojkovic, Nicholas C P Cross, Henrik Hjorth-Hansen, Andreas Hochhaus, Hagop Kantarjian, Jeffrey H Lipton, Hemant Malhotra, Dietger Niederwieser, Jerald Radich, Philippe Rousselot, Susanne Saussele, Charles A Schiffer, Richard Silver, Simona Soverini, Leif Stenke, Anna Turkina, Luis Felipe Casado, Fausto Castagnetti, Francisco Cervantes, Richard E Clark, Jorge Cortes, Michael Deininger, Timothy P Hughes, Jeroen Janssen, Qian Jiang, Dong-Wook Kim, Richard A Larson, Francois X Mahon, Michael Mauro, Jiri Mayer, Franck E Nicolini, Fabrizio Pane, Delphine Rea, Johan Richter, Gianantonio Rosti, Giuseppe Saglio, Rüdiger Hehlmann

Faculty, Staff and Student Publications

In this 5th version of the European LeukemiaNet guidance for adult patients, there are important changes in several areas of management based on evidence available since 2020, including the World Health Organisation's reclassification of CML as a biphasic disease. Previous advice to switch the tyrosine kinase inhibitor (TKI) on failure of molecular milestones, is modified to better account for individual patient circumstances. Our recommendations are summarized in tables designed to be read in conjunction with the text which offers justification and additional advice. We describe decision-making for first-line treatment, both in available drugs and their initial dosing. Similarly we elaborate …

Addressing Challenges In Developing Treatments For Inherited Retinal Diseases: Recommendations From The Third Monaciano Symposium, Debra A Thompson, K Thiran Jayasundera, Oleg Alekseev, Robin R Ali, Alessia Amato, Vadim Y Arshavsky, Isabelle S Audo, Alberto Auricchio, James W B Bainbridge, Eyal Banin, Cagri G Besirli, David G Birch, Kari E Branham, Artur V Cideciyan, Stephen P Daiger, Jacque L Duncan, Abigail T Fahim, John G Flannery, Roberto Gattegna, John R Heckenlively, Elise Héon, Alessandro Iannaccone, Naheed W Khan, Samer Khateb, Henry J Klassen, Bart P Leroy, Dario Marangoni, Michel Michaelides, David C Musch, Mark E Pennesi, Simon M Petersen-Jones, Eric A Pierce, Rajesh C Rao, José-Alain Sahel, Paul A Sieving, Enrica Strettoi, Cameron R Strong, Thomas J Wubben, Paul Yang, David N Zacks

Faculty, Staff and Student Publications

Over the past decade, efforts focused on developing genetic therapies for inherited retinal diseases have advanced steadily to clinical trials and the development of a treatment, fueling optimism for the potential of precision medicines to provide safe and effective therapies for these rare conditions. Although several ongoing programs remain poised for success, numerous challenges have negatively impacted the ability to obtain regulatory approvals. The present position paper briefly summarizes recent advances and challenges in developing therapeutics for inherited retinal diseases, and presents a set of recommendations for moving the field forward. The priorities identified are discussed in terms of progress …

Transcriptomic Analysis Of Localized High-Risk Prostate Cancer Improves Prognostication And Identifies Benefit From Adding Docetaxel To Definitive Radiotherapy With Androgen Suppression In The Nrg Oncology/Rtog 0521 Phase 3 Trial, Ryan M Phillips, James A Proudfoot, Elai Davicioni, Yang Liu, Daniel E Spratt, Jeff M Simko, Robert B Den, Alan Pollack, Seth A Rosenthal, A Oliver Sartor, Christopher J Sweeney, Gerhardt Attard, Leslie Longoria, Samir Patel, Michael W Straza, Jason A Efstathiou, Amit B Shah, Karen E Hoffman, Joseph P Rodgers, Howard M Sandler, Felix Y Feng, Phuoc T Tran

Faculty, Staff and Student Publications

Background and objective: NRG/RTOG 0521 randomized men with high-risk localized prostate cancer (PC) to androgen suppression (AS) and definitive radiotherapy (RT) ± docetaxel-based chemotherapy (CT). The overall survival (OS) benefit with CT initially reported was lost on longer follow-up. The Decipher genomic classifier (GC) measures multiple transcripts relevant to docetaxel action. Basal/luminal differentiation portends differential response to AS and CT for high-risk localized and metastatic hormone-sensitive PC. We validated the Decipher GC in pretreatment biopsy samples for risk stratification and examined basal-luminal subtyping to predict docetaxel response.

Methods: Decipher GC scores and basal-luminal cellular subtypes were generated for specimens from …

Efficacy And Safety Of Oral Decitabine/Cedazuridine In The Chronic Myelomonocytic Leukaemia Subpopulations From Phase 2 And 3 Studies, Michael R Savona, Olatoyosi Odenike, Gail J Roboz, Harshad Amin, Amy E Dezern, Elizabeth A Griffiths, Kim-Hien Dao, Amer M Zeidan, Bhavana Bhatnagar, Rena Buckstein, Brian Leber, Mary-Margaret Keating, Somedeb Ball, Aram Oganesian, Yuri Sano, Harold N Keer, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

DNA methyltransferase inhibitors (DNMTis) are commonly used in treating chronic myelomonocytic leukaemia (CMML); however, data from prospective studies of DNMTis in CMML are limited. The present analysis evaluated the efficacy, safety and pharmacodynamics of the oral DNMTi decitabine/cedazuridine in the subset of patients with CMML from the phase 2 and 3 trials, which led to the approval of this agent for myelodysplastic syndromes and CMML in the United States and Canada. Potential prognostic factors also were analysed. In all, 34 patients with CMML were screened and 33 were treated. Most patients (76% [n = 25]) had myelodysplastic type-CMML and 77% …

Bayesian Counterfactual Machine Learning Individualizes Radiation Modality Selection To Mitigate Immunosuppression, Duo Yu, Michael J Kane, Yiqing Chen, Steven H Lin, Radhe Mohan, Brian P Hobbs

Faculty, Staff and Student Publications

Purpose: Lymphocytes play critical roles in cancer immunity and tumor surveillance. Radiation-induced lymphopenia (RIL) is a common side effect observed in patients with cancer undergoing chemoradiation therapy (CRT), leading to impaired immunity and worse clinical outcomes. Although proton beam therapy (PBT) has been suggested to reduce RIL risk compared with intensity-modulated radiation therapy (IMRT), this study used Bayesian counterfactual machine learning to identify distinct patient profiles and inform personalized radiation modality choice.

Methods: A novel Bayesian causal inferential technique is introduced and applied to a matched retrospective cohort of 510 patients with esophageal cancer undergoing CRT to identify patient profiles …

Celebrating The Fifth Edition Of The International Symposium On Fungal Stress – Isfus, A Decade After Its 2014 Debut, Alene Alder-Rangel, Amanda E A Rangel, Arturo Casadevall, Asiya Gusa, Chaoyang Xue, Charles M Boone, Chris Todd Hittinger, Claudio A Masuda, Consuelo Olivares-Yañez, Deborah Bell-Pedersen, Erica J Washington, Gerhard Braus, Guilhem Janbon, István Pócsi, Jason E Stajich, Jay C Dunlap, Joan W Bennett, Joseph Heitman, Ling Lu, Lucia Landi, Mari L Shinohara, Maurizio Del Poeta, Mavis A Acheampong, Mia R Maltz, Michael C Lorenz, Minou Nowrousian, N Louise Glass, Nichole A Broderick, Nicolás Pedrini, Nir Osherov, R Blake Billmyre, Sabrina Sarrocco, Salomé Leibundgut-Landmann, Vânia Aparecida Vicente, Xiaorong Lin, Xin-Qing Zhao, Yong-Sun Bahn, Zachary A Lewis, Drauzio E N Rangel

Faculty, Staff and Student Publications

The Fifth International Symposium on Fungal Stress (ISFUS) brought together in Brazil many of the leaders in the field of fungal stress responses, from fourteen countries, for four days of outstanding science ranging from basic research to studies with agricultural, medical, industrial, and environmental significance. In addition to the excellent oral and poster presentations, the Symposium organisers ensured that all participants had ample opportunity to engage, socialise, and network to exchange ideas and share research. The conference was enhanced by the world-class venue near Iguazu Falls, probably the greatest natural phenomenon in South America.

12/15-Lipooxygenase Inhibition Reduces Microvessel Constriction And Microthrombi After Subarachnoid Hemorrhage In Mice, Ari Dienel, Sung Ha Hong, Hussein A Zeineddine, Sithara Thomas, Shafeeque C M, Dania A Jose, Kiara Torres, Jose Guzman, Andrew Dunn, P Kumar T, Gadiparthi N Rao, Spiros L Blackburn, Devin W Mcbride

Faculty, Staff and Student Publications

Impaired cerebral circulation, induced by blood vessel constrictions and microthrombi, leads to delayed cerebral ischemia after subarachnoid hemorrhage (SAH). 12/15-Lipooxygenase (12/15-LOX) overexpression has been implicated in worsening early brain injury outcomes following SAH. However, it is unknown if 12/15-LOX is important in delayed pathophysiological events after SAH. Since 12/15-LOX produces metabolites that induce inflammation and vasoconstriction, we hypothesized that 12/15-LOX leads to microvessel constriction and microthrombi formation after SAH, and thus, 12/15-LOX is an important target to prevent delayed cerebral ischemia. SAH was induced in C57BL/6 and 12/15-LOX−/− mice of both sexes by endovascular perforation. Expression of 12/15-LOX was assessed …

Development Of A Multi-Institutional Dataset To Validate A Novel Inflammatory Breast Cancer Diagnostic Score, Filipa Lynce, Samuel M Niman, Megumi Kai, Sean Ryan, Elizabeth Troll, Li Li, Kathy D Miller, Reshma Jagsi, Ginny Mason, Beth A Overmoyer, H T Carisa Le-Petross, Faina Nakhlis, Savitri Krishnamurthy, Beth T Harrison, Susie X Sun, Eren D Yeh, Jennifer R Bellon, Laura E Warren, Michael C Stauder, Meredith M Regan, Wendy A Woodward

Faculty, Staff and Student Publications

Background: Susan G. Komen, the Inflammatory Breast Cancer (IBC) Research Foundation, and the Milburn Foundation convened patient advocates, clinicians, and researchers to propose novel quantitative scoring rubrics for IBC diagnosis. In this study, we developed a multi-institutional clinical dataset to test and validate the proposed scoring system.

Methods: IBC (N = 988) and non-IBC (N = 332) cases were identified at 2 institutions with dedicated multidisciplinary IBC programs. The non-IBC cohort included consecutive cT4b and cT4c patients. Standard operating procedures (SOPs) were developed for all ambiguous findings and languages. Three different methods were used for the imputation of missing data, …

Human And Mouse Alzheimer's Seeds Differentially Affect Amyloid Deposition And Microglia-Dependent Plaque Response In Aged Mice, Juana Andreo-Lopez, Cristina Nuñez-Diaz, Kelly Do Huynh, Marie Minh Thu Nguyen, Celia Da Cunha, Francisco J Cantero-Molina, Cynthia Campos-Moreno, Stefania Zimbone, Francesco Bellia, Maria Laura Giuffrida, Laura Trujillo-Estrada, Juan Antonio Garcia-Leon, Miriam Bettinetti-Luque, Nazaret Gamez, Catalina Valdes, Rodrigo Morales, Stefania Forner, Alessandra C Martini, Antonia Gutierrez, Frank M Laferla, David Baglietto-Vargas

Faculty, Staff and Student Publications

Alzheimer's disease (AD) is a complex neurodegenerative proteinopathy in which Aβ and tau misfold and aggregate into entities that structurally unsettle native proteins, mimicking a prion-like or "seeding" process. These Aβ and tau "seeds" can arrange in different conformations or strains that might display distinct pathogenic properties. Furthermore, recent evidence suggests that microglia play a key role in the amyloidogenic event and can modulate the propagation and aggregation processes. Here, we employed histological and molecular approaches to determine whether seeds from human AD brains compared to those from transgenic mice (3xTg-AD) are more prone to induce Aβ and tau aggregates …

Cardiologists' Perceptions Of Cardiogenetic Testing And Management, W H Wilson Tang, Quan M Bui, Allison L Cirino, Lisa Dellefave-Castillo, Brendan J Floyd, Alejandra Guerchicoff, Marianna Guerchicoff, Amit V Khera, Joshua W Knowles, Kristen Lafayette, Andrew P Landstrom, Daria W Ma, Ana Morales, Kate M Orland, Daniel E Pineda-Alvarez, Siddharth K Prakash, Paul Theriot, Melissa Dempsey

Faculty, Staff and Student Publications

Background: Cardiogenetic testing has become clinically relevant as genetic insights increasingly contribute to the understanding and management of cardiovascular diseases of genetic origin. However, utilization of cardiogenetic testing remains variable and underutilized.

Objectives: The purpose of this study was to assess cardiologists' perceptions of cardiogenetic testing and identify relevant barriers, facilitators, educational needs, and clinical applications.

Methods: We surveyed 161 cardiologists using the American College of Cardiology CardioSurve Panel between March and April 2024.

Results: Among respondents, 80% reported that they have directly ordered or facilitated a referral for cardiogenetic testing for their patients. Generally, cardiologists from our testing group …

The Glycosyltransferase Poglut1 Regulates Muscle Stem Cell Development And Maintenance In Mice, Soomin Cho, Emilia Servián-Morilla, Victoria Navarro, Beatriz Rodriguez-Gonzalez, Youxi Yuan, Raquel Cano, Arjun A Rambhiya, Radbod Darabi, Robert S Haltiwanger, Carmen Paradas, Hamed Jafar-Nejad

Faculty, Staff and Students Publications

Mutations in protein O-glucosyltransferase 1 (POGLUT1) cause a recessive limb-girdle muscular dystrophy (LGMDR21) with reduced satellite cell number and NOTCH1 signaling in adult patient muscles and impaired myogenic capacity of patient-derived muscle progenitors. However, the in vivo roles of POGLUT1 in the development, function, and maintenance of satellite cells are not well understood. Here, we show that conditional deletion of mouse Poglut1 in myogenic progenitors leads to early lethality, postnatal muscle growth defects, reduced Pax7 expression, abnormality in muscle extracellular matrix, and impaired muscle repair. Poglut1-deficient muscle progenitors exhibit reduced proliferation, enhanced differentiation, and accelerated fusion into myofibers. Inducible loss …

Inhibition Of Methylthioadenosine Phosphorylase Protects From Experimental Acute Kidney Injury, Afaf Saliba, Yidong Chen, Jonathan W Nelson, Abhinav Vetcha, Wei Wei Wang, Li Kang, Nagarjunachary Ragi, Soumya Maity, Hamid Rabb, W Brian Reeves, Kumar Sharma

Faculty, Staff and Student Publications

Methylthioadenosine phosphorylase (MTAP) is a key enzyme in purine metabolism that may influence cellular responses to injury. We evaluated the effects of prophylactic MTAP inhibition in mouse models of ischemia-reperfusion and cisplatin-induced acute kidney injury (AKI). MTAP inhibition was confirmed by accumulation of methylthioadenosine (MTA). Treated mice showed reduced renal injury and decreased tubular damage. Transcriptomic analysis revealed protection from inflammatory and stress pathways, while maintaining oxidative phosphorylation, fatty acid metabolism, and epithelial integrity-related genes. Analysis of human single-cell RNA-seq data from the Kidney Precision Medicine Project indicated that MTAP is highly expressed in kidney injury marker-positive adaptive proximal tubule …

Early Treatment Engagement And Long-Term Smoking Abstinence Among Women With Cervical Intraepithelial Neoplasia Or Cervical Cancer, Charles E Hoogland, Steven K Sutton, Bethany Shorey Fennell, Vani N Simmons, Christine Vinci, Issam El Naqa, Ramzi G Salloum, Sanjay S Shete, Timothy Hembree, Damon J Vidrine, Jennifer I Vidrine

Faculty, Staff and Student Publications

Introduction: Cancer survivors who quit smoking have improved treatment response and decreased mortality. Although data indicate that greater tobacco cessation treatment engagement leads to better cessation outcomes in cancer survivors, little is known about how different tobacco treatment engagement patterns influence long-term cessation success. To help address this issue, this study examined how tobacco treatment engagement patterns predict cessation outcomes through 18 months and identified baseline participant characteristics predictive of treatment engagement patterns.

Methods: Data from a smoking-cessation RCT among women with a history of cervical intraepithelial neoplasia or cervical cancer comparing a 12-month, 6-session motivation and problem solving phone …

Associations Between Prostate Cancer And Dementia: A Nationwide Study In Sweden, Casey Crump, Pär Stattin, James D Brooks, Jan Sundquist, Jingkai Wei, Weiva Sieh, Kristina Sundquist

Faculty, Staff and Student Publications

Background and objective: Prostate cancer (PC) and dementia may commonly co-occur; yet, prior evidence for bidirectional associations is inconsistent. This study aims to determine the associations between PC and dementia in large population-based studies, which may further inform clinical care.

Methods: To assess the dementia risk in men with PC, a national cohort study was conducted in 178 746 men diagnosed with PC in 1998-2017 and 1 787 460 age-matched control men in Sweden without prior dementia. Cox regression was used to estimate hazard ratios (HRs) for Alzheimer's disease (AD) and vascular dementia (VaD) through 2018. Subanalyses explored differences by …

Master Protocol Design With Hybrid Control For Efficient Early-Phase Trial Consolidation, Alexander M Kaizer, Xiaojiang Zhan, Eric Baron, Rui Sammi Tang, David S Hong, Brian P Hobbs

Faculty, Staff and Student Publications

Purpose: Master protocols represent transformations, enabling multiple therapies or diseases under a single protocol. These designs streamline therapeutic development by reducing redundancies. Suited for evolving fields such as oncology and global emergencies such as the COVID-19 pandemic, master protocols have been exemplified by studies such as RECOVERY, Solidarity, and I-SPY 2, which accelerated effective treatment identification (with I-SPY 2 focused on molecular subtypes). Recent oncology examples, such as MORPHEUS, evaluate immunotherapy combinations with shared controls. Despite advantages, their application in early-phase oncology remains underutilized amid growing regulatory emphasis on randomization for robust evidence.

Methods: US Food and Drug Administration (FDA) …

White Matter Abnormalities And Cognition In Aging And Alzheimer Disease, Christopher Peter, Aditi Sathe, Niranjana Shashikumar, Kimberly R Pechman, Abigail W Workmeister, T Bryan Jackson, Yuankai Huo, Shubhabrata Mukherjee, Jesse Mez, Logan C Dumitrescu, Katherine A Gifford, Corey J Bolton, Leslie S Gaynor, Shannon L Risacher, Lori L Beason-Held, Yang An, Konstantinos Arfanakis, Guray Erus, Christos Davatzikos, Duygu Tosun-Turgut, Mohamad Habes, Di Wang, Arthur W Toga, Paul M Thompson, Panpan Zhang, Kurt G Schilling, Marilyn Albert, Walter Kukull, Sarah A Biber, Bennett A Landman, Barbara B Bendlin, Sterling C Johnson, Julie Schneider, Lisa L Barnes, David A Bennett, Angela L Jefferson, Susan M Resnick, Andrew J Saykin, Paul K Crane, Michael L Cuccaro, Timothy J Hohman, Derek B Archer, Dimitrios Zaras, Yisu Yang, Alaina Durant, Praitayini Kanakaraj, Michael E Kim, Chenyu Gao, Nancy R Newlin, Karthik Ramadass, Nazirah Mohd Khairi, Zhiyuan Li, Tianyuan Yao, Seo-Eun Choi, Brandon Klinedinst, Michael L Lee, Phoebe Scollard, Emily H Trittschuh, Elizabeth A Sanders

Faculty, Staff and Student Publications

Importance: There has yet to be a large-scale study quantifying the association between white matter microstructure and cognitive performance and decline in aging and Alzheimer disease (AD).

Objective: To investigate the associations between tract-specific white matter microstructure and cognitive performance and decline in aging and AD-related cognitive impairment.

Design setting and participants: This prognostic study of aging and AD, a secondary data analysis of multisite cohort studies, acquired data from 9 cohorts between September 2002 and November 2022. Participants were eligible if they had diffusion-weighted magnetic resonance imaging (dMRI) data, domain-specific cognitive composite z scores, demographic and clinical data, were …

Complete Response To Trastuzumab-Deruxtecan (Enhertu, T-Dxd) In Her2-Positive Stage Ivb Uterine Carcinosarcoma, Michael Kim, Amma Asare, Jamie L Dockery, Nadia Hameed, Travis T Sims

Faculty, Staff and Student Publications

Objectives: To report a case of complete response to trastuzumab-deruxtecan (T-DXd) in a patient with HER2-positive stage IVB uterine carcinosarcoma, and to contextualize this within evolving therapy for HER2-positive gynecologic malignancies.

Methods: We present the clinical course of a 62-year-old woman with a history of multiple prior malignancies, diagnosed with stage IVB uterine carcinosarcoma exhibiting HER2 overexpression. Following optimal cytoreductive surgery and first-line carboplatin, paclitaxel, and trastuzumab, the patient developed platinum-resistant recurrence. She was subsequently treated with T-DXd, and received serial imaging and clinical monitoring.

Results: The patient achieved a partial response by cycle 4 of T-DXd, with subsequent scans …

Nanotechnology For Immuno-Oncology, Adam J Grippin, Daeyong Lee, Eileen E Parkes, Wen Jiang, Betty Y S Kim

Faculty, Staff and Student Publications

Although the first generation of cancer immunotherapeutics produced unprecedented improvements in clinical outcomes for individuals with cancer, novel strategies to increase treatment specificity, delivery efficiency and pharmacokinetics are still needed. In this Review, we describe the potential advantages and current limitations of nanomaterials for cancer immunotherapy and highlight rational uses of nanosystems to generate potent and durable antitumor immune responses. We close with a review of the current state of clinical development of nanomedicine for cancer immunotherapy.

Consensus Statement On The Prevention And Management Of Complications Of Fully Ablative Laser Resurfacing Of The Face, Bianca Y Kang, Joel L Cohen, Roy Geronemus, Suzanne L Kilmer, Edward Victor Ross, Elizabeth L Tanzi, Jill S Waibel, Brian J F Wong, Murad Alam, Macrene Alexiades, Kenneth A Arndt, Mathew Avram, Ashish C Bhatia, Brian Stuart Biesman, Jason D Bloom, A Jay Burns, Henry H L Chan, Catherine M Digiorgio, Jeffrey S Dover, Sam Fathizadeh, Sara C Esteves, Michael H Gold, Gerald N Goldberg, Merete Haedersdal, Elika Hoss, Omar A Ibrahimi, H Ray Jalian, Kristen M Kelly, Woraphong Manuskiatti, Lisa A Marks, Girish S Munavalli, Jason N Pozner, Chris W Robb, Anthony M Rossi, Nazanin Saedi, Peter R Shumaker, Kelly Stankiewicz, Molly Wanner, Douglas C Wu, Adam J Wulkan, Arisa Ortiz

Faculty, Staff and Student Publications

Objectives: To achieve consensus among expert laser surgeons on standards for the prevention and management of adverse events from fully ablative laser resurfacing of the face.

Materials and methods: Delphi study with two rounds of ratings and revisions until consensus was achieved. The draft set of statements was developed by a steering committee based on expert clinical experience. This was followed by two rounds of rating and revisions completed by an expert panel, then a virtual consensus meeting. In both rounds, respondents rated the draft statements on a 9-point Likert scale (1 = strongly disagree; 9 = strongly agree) and …

Provider Attitudes And Perspectives On Rehabilitation For Pediatric Cancer Patients, Maria C Swartz, Eduardo Gonzalez Villarreal, Keri Schadler, Donna Kelly, Alakh P Rajan, Clark Andersen, Shiming Zhang, Stephanie J Wells, Amy Heaton, Karen M Moody

Faculty, Staff and Student Publications

PurposeTwenty percent of childhood cancer survivors experience physical function impairments, and ∼75% develop a chronic health condition. Physical and occupational therapists (PT/OTs) can mitigate these late effects, yet few children receive cancer rehabilitation (CR). This research aimed to identify provider attitudes and perspectives towards CR services for children across inpatient and outpatient settings at a cancer center.MethodsThree cardiac rehabilitation instruments were adapted to evaluate knowledge, attitudes, and perceptions regarding CR delivery. Descriptive statistics were used to summarize participant survey results.ResultsTwenty administrators, 20 physicians/advanced practice providers (APPs), and 20 PT/OTs completed surveys. All disciplines strongly agreed on the value of CR …

The Significance Of Detecting An Unusual Myeloblast Immunophenotype In A Presumptive Clinical Diagnosis Of Myelodysplastic Syndromes, Fnu Sameeta, Wei Wang, Fatima Zahra Jelloul, Okechukwu V Nwogbo, Beenu Thakral, Jie Xu, Shaoying Li, Chi Young Ok, Guilin Tang, Fuli Jia, L Jeffrey Medeiros, Sanam Loghavi, Jeffrey L Jorgensen, Sa A Wang

Faculty, Staff and Student Publications

Context.—: Blasts in myelodysplastic syndromes (MDSs) typically have a primitive myeloid immunophenotype (CD34+CD117+CD13+CD33+HLA-DR+). On rare occasions, blasts were found to be CD34 negative or minimally expressed in a presumptive MDS.

Objective.—: To investigate the occurrence of these cases, and to examine any unique molecular genetic features, and clinical relevance.

Design.—: More than 2000 flow cytometry immunophenotyping tests for MDS performed during a 5-year period were retrospectively reviewed. Chronic myelomonocytic leukemia and overt acute myeloid leukemia (AML) (≥20% blasts) were excluded.

Results.—: Approximately 800 cases had abnormal myeloblasts consistent with myeloid neoplasms; 96% of cases showed a typical primitive phenotype, but …

Bard: A Seamless Two-Stage Dose Optimization Design Integrating Backfill And Adaptive Randomization, Yixuan Zhao, Rachael Liu, Jianchang Lin, Ying Yuan

Faculty, Staff and Student Publications

One common approach for dose optimization is a two-stage design, which initially conducts dose escalation to identify the maximum tolerated dose, followed by a randomization stage where patients are assigned to two or more doses to further assess and compare their risk-benefit profiles to identify the optimal dose. A limitation of this approach is its requirement for a relatively large sample size. To address this challenge, we propose a seamless two-stage design, BARD (Backfill and Adaptive Randomization for Dose Optimization), which incorporates two key features to reduce sample size and shorten trial duration. The first feature is the integration of …