Genetic Phenomena Commons^™

Effects Of Kras Genetic Interactions On Outcomes In Cancers Of The Lung, Pancreas, And Colorectum, Isabella N Grabski, John V Heymach, Kenneth L Kehl, Scott Kopetz, Ken S Lau, Gregory J Riely, Deborah Schrag, Rona Yaeger, Rafael A Irizarry, Kevin M Haigis

Faculty, Staff and Student Publications

Background: KRAS is among the most commonly mutated oncogenes in cancer, and previous studies have shown associations with survival in many cancer contexts. Evidence from both clinical observations and mouse experiments further suggests that these associations are allele- and tissue-specific. These findings motivate using clinical data to understand gene interactions and clinical covariates within different alleles and tissues.

Methods: We analyze genomic and clinical data from the AACR Project GENIE Biopharma Collaborative for samples from lung, colorectal, and pancreatic cancers. For each of these cancer types, we report epidemiological associations for different KRAS alleles, apply principal component analysis (PCA) to …

Polatuzumab Vedotin, Venetoclax, And An Anti-Cd20 Monoclonal Antibody In Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma, Simona F Shaitelman, Wendy A Woodward

Faculty, Staff and Student Publications

Neoadjuvant chemotherapy plus immunotherapy for triple-negative breast cancer (TNBC) is associated with improved but incomplete response. In this issue of Cancer Cell, Shiao et al. characterize longitudinal biopsies from a window of opportunity study with single-cell RNA sequencing (scRNA-seq) and spatial proteomic profiling and elucidate synergy between radiotherapy (RT) and pembrolizumab.

Product Attributes Of Car T-Cell Therapy Differentially Associate With Efficacy And Toxicity In Second-Line Large B-Cell Lymphoma (Zuma-7), Simone Filosto, Saran Vardhanabhuti, Miguel A Canales, Xavier Poiré, Lazaros J Lekakis, Sven De Vos, Craig A Portell, Zixing Wang, Christina To, Marco Schupp, Soumya Poddar, Tan Trinh, Carmen M Warren, Ethan G Aguilar, Justin Budka, Paul Cheng, Justin Chou, Adrian Bot, Rhine R Shen, Jason R Westin

Faculty, Staff and Student Publications

Treatment resistance and toxicities remain a risk following chimeric antigen receptor (CAR) T-cell therapy. Herein, we report pharmacokinetics, pharmacodynamics, and product and apheresis attributes associated with outcomes among patients with relapsed/refractory large B-cell lymphoma (LBCL) treated with axicabtagene ciloleucel (axi-cel) in ZUMA-7. Axi-cel peak expansion associated with clinical response and toxicity, but not response durability. In apheresis material and final product, a naive T-cell phenotype (CCR7+CD45RA+) expressing CD27 and CD28 associated with improved response durability, event-free survival, progression-free survival, and a lower number of prior therapies. This phenotype was not associated with high-grade cytokine release syndrome (CRS) or neurologic events. …

Dimerization Of The 4ig Isoform Of B7-H3 In Tumor Cells Mediates Enhanced Proliferation And Tumorigenic Signaling, Margie N Sutton, Sarah E Glazer, Riccardo Muzzioli, Ping Yang, Seth T Gammon, David Piwnica-Worms

Faculty, Staff and Student Publications

B7-H3 (CD276) has two isoforms (2Ig and 4Ig), no confirmed cognate receptor, and physiological functions that remain elusive. While differentially expressed on many solid tumors correlating with poor survival, mechanisms of how B7-H3 signals in cis (tumor cell) versus in trans (immune cell co-regulator) to elicit pro-tumorigenic phenotypes remain poorly defined. Herein, we characterized a tumorigenic and signaling role for tumor cell-expressed 4Ig-B7-H3, the dominant human isoform, in gynecological cancers that could be abrogated upon CRISPR/Cas9 knockout of B7-H3; tumorigenesis was rescued upon re-expression of 4Ig-B7-H3. Size exclusion chromatography revealed dimerization states for the extracellular domains of both human 4Ig- …

Pancanqtlv20: A Comprehensive Resource For Expression Quantitative Trait Loci Across Human Cancers, Chengxuan Chen, Yuan Liu, Mei Luo, Jingwen Yang, Yamei Chen, Runhao Wang, Joseph Zhou, Yong Zang, Lixia Diao, Leng Han

Faculty, Staff and Student Publications

Expression quantitative trait locus (eQTL) analysis is a powerful tool used to investigate genetic variations in complex diseases, including cancer. We previously developed a comprehensive database, PancanQTL, to characterize cancer eQTLs using The Cancer Genome Atlas (TCGA) dataset, and linked eQTLs with patient survival and GWAS risk variants. Here, we present an updated version, PancanQTLv2.0 (https://hanlaboratory.com/PancanQTLv2/), with advancements in fine-mapping causal variants for eQTLs, updating eQTLs overlapping with GWAS linkage disequilibrium regions and identifying eQTLs associated with drug response and immune infiltration. Through fine-mapping analysis, we identified 58 747 fine-mapped eQTLs credible sets, providing mechanic insights of gene regulation in …

Contributions Of The Microbiome-Derived Metabolome For Risk Assessment And Prognostication Of Pancreatic Cancer, Ricardo A León-Letelier, Rongzhang Dou, Jody Vykoukal, Michele T Yip-Schneider, Anirban Maitra, Ehsan Irajizad, Ranran Wu, Jennifer B Dennison, Kim-An Do, Jianjun Zhang, C Max Schmidt, Samir Hanash, Johannes F Fahrmann

Faculty, Staff and Student Publications

Background: Increasing evidence implicates microbiome involvement in the development and progression of pancreatic ductal adenocarcinoma (PDAC). Studies suggest that reflux of gut or oral microbiota can lead to colonization in the pancreas, resulting in dysbiosis that culminates in release of microbial toxins and metabolites that potentiate an inflammatory response and increase susceptibility to PDAC. Moreover, microbe-derived metabolites can exert direct effector functions on precursors and cancer cells, as well as other cell types, to either promote or attenuate tumor development and modulate treatment response.

Content: The occurrence of microbial metabolites in biofluids thereby enables risk assessment and prognostication of PDAC, …

Mir126-Targeted-Nanoparticles Combined With Pi3k/Akt Inhibitor As A New Strategy To Overcome Melanoma Resistance, Maria Beatrice Arasi, Gabriele De Luca, Laura Chronopoulou, Francesca Pedini, Eleonora Petrucci, Michela Flego, Annarita Stringaro, Marisa Colone, Luca Pasquini, Massimo Spada, Valentina Lulli, Maria Chiara Perrotta, George Adrian Calin, Cleofe Palocci, Mauro Biffoni, Federica Felicetti, Nadia Felli

Faculty, Staff and Student Publications

Metastatic melanoma poses significant challenges as a highly lethal disease. Despite the success of molecular targeting using BRAFV600E inhibitors (BRAFis) and immunotherapy, the emergence of early recurrence remains an issue and there is the need for novel therapeutic approaches. This study aimed at creating a targeted delivery system for the oncosuppressor microRNA 126 (miR126) and testing its effectiveness in combination with a phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (AKT) inhibitor for treating metastatic melanoma resistant to BRAFis. To achieve this, we synthesized chitosan nanoparticles containing a chemically modified miR126 sequence. These nanoparticles were further functionalized with an antibody specific to …

Class Ii Hla-Drb4 Is A Predictive Biomarker For Survival Following Immunotherapy In Metastatic Non-Small Cell Lung Cancer, Cindy Y Jiang, Lili Zhao, Michael D Green, Shashidhar Ravishankar, Andrea M H Towlerton, Anthony J Scott, Malini Raghavan, Matthew F Cusick, Edus H Warren, Nithya Ramnath

Faculty, Staff and Student Publications

Immune checkpoint inhibitors (ICI) are important treatment options for metastatic non-small cell lung cancer (mNSCLC). However, not all patients benefit from ICIs and can experience immune-related adverse events (irAEs). Limited understanding exists for germline determinants of ICI efficacy and toxicity, but Human Leukocyte Antigen (HLA) genes have emerged as a potential predictive biomarker. We performed HLA typing on 85 patients with mNSCLC, on ICI therapy and analyzed the impact of HLA Class II genotype on progression free survival (PFS), overall survival (OS), and irAEs. Most patients received pembrolizumab (83.5%). HLA-DRB4 genotype was seen in 34/85 (40%) and its presence correlated …

Integrated Multi-Omics Analyses Identify Anti-Viral Host Factors And Pathways Controlling Sars-Cov-2 Infection, Jiakai Hou, Yanjun Wei, Jing Zou, Roshni Jaffery, Long Sun, Shaoheng Liang, Ningbo Zheng, Ashley M Guerrero, Nicholas A Egan, Ritu Bohat, Si Chen, Caishang Zheng, Xiaobo Mao, S Stephen Yi, Ken Chen, Daniel J Mcgrail, Nidhi Sahni, Pei-Yong Shi, Yiwen Chen, Xuping Xie, Weiyi Peng

Faculty, Staff and Student Publications

Host anti-viral factors are essential for controlling SARS-CoV-2 infection but remain largely unknown due to the biases of previous large-scale studies toward pro-viral host factors. To fill in this knowledge gap, we perform a genome-wide CRISPR dropout screen and integrate analyses of the multi-omics data of the CRISPR screen, genome-wide association studies, single-cell RNA-Seq, and host-virus proteins or protein/RNA interactome. This study uncovers many host factors that are currently underappreciated, including the components of V-ATPases, ESCRT, and N-glycosylation pathways that modulate viral entry and/or replication. The cohesin complex is also identified as an anti-viral pathway, suggesting an important role of …

Unraveling The Intercellular Communication Disruption And Key Pathways In Alzheimer’S Disease: An Integrative Study Of Single-Nucleus Transcriptomes And Genetic Association, Andi Liu, Brisa S Fernandes, Citu Citu, Zhongming Zhao

Faculty, Staff and Student Publications

BACKGROUND: Recently, single-nucleus RNA-seq (snRNA-seq) analyses have revealed important cellular and functional features of Alzheimer's disease (AD), a prevalent neurodegenerative disease. However, our knowledge regarding intercellular communication mediated by dysregulated ligand-receptor (LR) interactions remains very limited in AD brains.

METHODS: We systematically assessed the intercellular communication networks by using a discovery snRNA-seq dataset comprising 69,499 nuclei from 48 human postmortem prefrontal cortex (PFC) samples. We replicated the findings using an independent snRNA-seq dataset of 56,440 nuclei from 18 PFC samples. By integrating genetic signals from AD genome-wide association studies (GWAS) summary statistics and whole genome sequencing (WGS) data, we prioritized …

Facilitating Clinical Information Extraction With Synthetic Data And Ontology Using Large Language Models, Yan Hu, Huan He, Qingyu Chen, Xiaoqian Jiang, Kirk Roberts, Hua Xu

Faculty, Staff and Student Publications

The rapid growth of unstructured clinical text in electronic health records necessitates robust information extraction systems, yet their development is hindered by the scarcity of high-quality annotated data. This study explores the potential of large language models to generate synthetic data for clinical named entity recognition and examines its impact on model performance. We propose a novel framework that integrates self-verified synthetic data generation with domain-specific semantic mapping using SNOMED-CT. By leveraging GPT-4o-mini for synthetic data creation and refining its quality through iterative verification and anomaly detection, we systematically evaluate the influence of synthetic data quality and quantity on fine-tuning …

Design And Implementation Of Multicenter Pediatric And Congenital Studies With Cardiovascular Magnetic Resonance: Big Data In Smaller Bodies, Michael P Dilorenzo, Simon Lee, Rahul H Rathod, Francesca Raimondi, Kanwal M Farooqi, Supriya S Jain, Margaret M Samyn, Tiffanie R Johnson, Laura J Olivieri, Mark A Fogel, Wyman W Lai, Pierangelo Renella, Andrew J Powell, Sujatha Buddhe, Caitlin Stafford, Jason N Johnson, Willem A Helbing, Kuberan Pushparajah, Inga Voges, Vivek Muthurangu, Kimberley G Miles, Gerald Greil, Colin J Mcmahon, Timothy C Slesnick, Brian M Fonseca, Shaine A Morris, Jonathan H Soslow, Lars Grosse-Wortmann, Rebecca S Beroukhim, Heynric B Grotenhuis

Faculty, Staff and Student Publications

Cardiovascular magnetic resonance (CMR) has become the reference standard for quantitative and qualitative assessment of ventricular function, blood flow, and myocardial tissue characterization. There is a preponderance of large CMR studies and registries in adults; However, similarly powered studies are lacking for the pediatric and congenital heart disease (PCHD) population. To date, most CMR studies in children are limited to small single or multicenter studies, thereby limiting the conclusions that can be drawn. Within the PCHD CMR community, a collaborative effort has been successfully employed to recognize knowledge gaps with the aim to embolden the development and initiation of high-quality, …

Dysregulation Of Epigenetic Modifications In Inborn Errors Of Immunity, Zhongyao Xiao, Rongjing He, Zihan Zhao, Taiping Chen, Zhengzhou Ying

Faculty, Staff and Student Publications

Inborn errors of immunity (IEIs) are a group of typically monogenic disorders characterized by dysfunction in the immune system. Individuals with these disorders experience increased susceptibility to infections, autoimmunity and malignancies due to abnormal immune responses. Epigenetic modifications, including DNA methylation, histone modifications and chromatin remodeling, have been well explored in the regulation of immune cell development and effector function. Aberrant epigenetic modifications can disrupt gene expression profiles crucial for immune responses, resulting in impaired immune cell differentiation and function. Dysregulation of these processes caused by mutations in genes involving in epigenetic modifications has been associated with various IEIs. In …

Rragd-Associated Autosomal Dominant Kidney Hypomagnesemia With Cardiomyopathy: A Review On The Clinical Manifestations And Therapeutic Options, Francesco Trepiccione, Irene Sambri, Barbara Ruggiero, Francesco Emma, Andrea Ballabio, Giulia Florio, Ines Vanderheyden, Anna Iervolino, François Jouret

Duncan NRI Faculty and Staff Publications

Background: A hereditary condition primarily affecting the kidneys and heart has newly been identified: the RRAGD-associated autosomal dominant kidney hypomagnesemia with cardiomyopathy (ADKH-RRAGD). This disorder is characterized by renal loss of magnesium and potassium, coupled with varying degrees of cardiac dysfunction. These range from arrhythmias to severe dilated cardiomyopathy, which may require heart transplantation. Mutations associated with RRAGD significantly disrupt the non-canonical branch of the mechanistic target of rapamycin complex 1 pathway. This disruption hinders the nuclear translocation and transcriptional activity of the transcription factor EB a crucial regulator of lysosomal and autophagic function.

Summary: All identified RRAGD variants compromise …

Fgf5, Evelyn A Carrion, Malcolm M Moses, Richard R Behringer

Faculty, Staff and Student Publications

FGF5 functions as a negative regulator of the hair cycle in mammals. It is expressed in the outer root sheath of hair follicles during the late anagen phase of the hair cycle. It functions as a signaling molecule, mediating the transition of the anagen growth phase to catagen regression phase of the hair cycle. Spontaneous and engineered FGF5 mutations in mammalian animal models result in long hair phenotypes. In humans, inherited FGF5 mutations result in trichomegaly (long eyelashes). Knockdown of fgf5 in zebrafish embryos results in inner ear alterations. Alterations in FGF5 expression are also associated with various human pathologies.

Sudden Unexpected Intrapartum Death And Left Ventricular Noncompaction Involving The Right Ventricle, Giulia Ottaviani, Tobia Tomasello, Francesca Boggio, Letterio Runza, Alessandro Del Gobbo, L Maximilian Buja

Faculty, Staff and Student Publications

Left ventricular noncompaction (LVNC), involving mainly the right ventricle, is a rare form of congenital heart disorder characterized by a developmental arrest in myocardial compaction, resulting in a spongy appearance of the myocardium, mainly of the right ventricle, rarely detected in fetuses. We report the case of a female fetus with a gestational age of 41+4 weeks who came to our attention for intrapartum sudden unexpected death, resulting in stillbirth. The ventricular walls, particularly the right ventricular wall, appeared thick, hypertrabeculated and spongy, leading to the diagnosis of LVNC involving mainly the right ventricle. The atrioventricular node and His bundle …

Chronic Lymphocytic Leukemia: Disease Biology, Stefan Koehrer, Jan A Burger

Faculty, Staff and Student Publications

Background: B-cell receptor (BCR) signaling is crucial for normal B-cell development and adaptive immunity. In chronic lymphocytic leukemia (CLL), the malignant B cells display many features of normal mature B lymphocytes, including the expression of functional B-cell receptors (BCRs). Cross talk between CLL cells and the microenvironment in secondary lymphatic organs results in BCR signaling and BCR-driven proliferation of the CLL cells. This critical pathomechanism can be targeted by blocking BCR-related kinases (BTK, PI3K, spleen tyrosine kinase) using small-molecule inhibitors. Among these targets, Bruton tyrosine kinase (BTK) inhibitors have the highest therapeutic efficacy; they effectively block leukemia cell proliferation and …

On The Relative Conservativeness Of Bayesian Logistic Regression Method In Oncology Dose-Finding Studies, Cheng-Han Yang, Guanghui Cheng, Ruitao Lin

Faculty, Staff and Student Publications

The Bayesian logistic regression method (BLRM) is a widely adopted and flexible design for finding the maximum tolerated dose in oncology phase I studies. However, the BLRM design has been criticized in the literature for being overly conservative due to the use of the overdose control rule. Recently, a discussion paper titled "Improving the performance of Bayesian logistic regression model with overall control in oncology dose-finding studies" in Statistics in Medicine has proposed an overall control rule to address the "excessive conservativeness" of the standard BLRM design. In this short communication, we discuss the relative conservativeness of the standard BLRM …

Systematic Review And Meta-Analysis Of Acupuncture For Modulation Of Immune And Inflammatory Markers In Cancer Patients, Wenli Liu, Baisong Zhong, Richard W Wagner, M Kay Garcia, Jennifer L Mcquade, Wen Huang, Yisheng Li, Graciela M Nogueras Gonzalez, Michael R Spano, Alessandro Cohen, Yimin Geng, Lorenzo Cohen

Faculty, Staff and Student Publications

Introduction: Inflammation is associated with tumor initiation, and existing tumors are associated with immune suppression locally and systemically. Cancer treatment is also associated with immune suppression. This review evaluates evidence related to the use of acupuncture for modulation of inflammation and the immune system in cancer patients.

Methods: Nine databases were searched for prospective, randomized, controlled trials evaluating the use of acupuncture for modulation of the immune system in cancer patients through March 2024. Only studies involving needle insertion into acupuncture points were included. No language limitations were applied. Studies were assessed for risk of bias (ROB) according to Cochrane …

Pancreatic Cancer Action Network's Spark: A Cloud-Based Patient Health Data And Analytics Platform For Pancreatic Cancer, Kawther Abdilleh, Omar Khalid, Dennis Ladnier, Wenshuai Wan, Sara Seepo, Garrett Rupp, Valentin Corelj, Zelia F Worman, Divya Sain, Jack Digiovanna, Bruce Press, Satty Chandrashekhar, Eric Collisson, Karen Y Cui, Anirban Maitra, Paul A Rejto, Kevin P White, Lynn Matrisian, Sudheer Doss

Faculty, Staff and Student Publications

Purpose: Pancreatic cancer currently holds the position of third deadliest cancer in the United States and the 5-year survival rate is among the lowest for major cancers at just 12%. Thus, continued research efforts to better understand the clinical and molecular underpinnings of pancreatic cancer are critical to developing both early detection methodologies as well as improved therapeutic options. This study introduces Pancreatic Cancer Action Network's (PanCAN's) SPARK, a cloud-based data and analytics platform that integrates patient health data from the PanCAN's research initiatives and aims to accelerate pancreatic cancer research by making real-world patient health data and analysis tools …

Leptomeningeal Disease In Melanoma: An Update On The Developments In Pathophysiology And Clinical Care, Inna Smalley, Adrienne Boire, Priscilla Brastianos, Harriet M Kluger, Eva Hernando-Monge, Peter A Forsyth, Kamran A Ahmed, Keiran S M Smalley, Sherise Ferguson, Michael A Davies, Isabella C Glitza Oliva

Faculty, Staff and Student Publications

Leptomeningeal disease (LMD) remains a major challenge in the clinical management of metastatic melanoma patients. Outcomes for patient remain poor, and patients with LMD continue to be excluded from almost all clinical trials. However, recent trials have demonstrated the feasibility of conducting prospective clinical trials in these patients. Further, new insights into the pathophysiology of LMD are identifying rational new therapeutic strategies. Here we present recent advances in the understanding of, and treatment options for, LMD from metastatic melanoma. We also annotate key areas of future focus to accelerate progress for this challenging but emerging field.

Myeloid Lineage Switch In Kmt2a- Rearranged Acute Lymphoblastic Leukemia Treated With Lymphoid Lineagedirected Therapies, Alex Bataller, Tareq Abuasab, David Mccall, Wei Wang, Branko Cuglievan, Ghayas C Issa, Elias Jabbour, Nicholas Short, Courtney D Dinardo, Guilin Tang, Guillermo Garcia-Manero, Hagop M Kantarjian, Koji Sasaki

Faculty, Staff and Student Publications

No abstract provided.

Editorial: Mathematical Modeling And Computational Predictions In Oncoimmunology, Vladimir A Kuznetsov, Heiko Enderling, Mark Chaplain

Faculty, Staff and Student Publications

No abstract provided.

The Impact Of Psychological Strengths On Veteran Populations' Mental Health Trajectories During The Covid-19 Pandemic, Amanda Mccleery, Jonathan K Wynn, Derek M Novacek, Eric A Reavis, Damla Senturk, Catherine A Sugar, Jack Tsai, Michael F Green

Faculty, Staff and Student Publications

Purpose: Mental health trajectories during the COVID-19 pandemic have been examined in Veterans with tenuous social connections, i.e., those with recent homelessness (RHV) or a psychotic disorder (PSY), and in control Veterans (CTL). We test potential moderating effects on these trajectories by psychological factors that may help individuals weather the socio-emotional challenges associated with the pandemic (i.e., 'psychological strengths').

Methods: We assessed 81 PSY, 76 RHV, and 74 CTL over 5 periods between 05/2020 and 07/2021. Mental health outcomes (i.e., symptoms of depression, anxiety, contamination concerns, loneliness) were assessed at each period, and psychological strengths (i.e., a composite score based …

Metformin In Conjunction With Stereotactic Radiotherapy For Early-Stage Non-Small Cell Lung Cancer: Long-Term Results Of A Prospective Phase Ii Clinical Trial, Molly K Tate, Mike Hernandez, Joe Y Chang, Steven H Lin, Zhongxing Liao, Suja M Koshy, Heath D Skinner, Stephen G Chun

Faculty, Staff and Student Publications

Background/aim: Non-small cell lung cancer (NSCLC) is increasingly detected in early stages and there is interest in improving outcomes with stereotactic body radiotherapy (SBRT). As metformin affects NSCLC signaling pathways, it might alter the metabolism of NSCLC treated with SBRT. This study investigated the long-term outcomes of a phase II clinical trial evaluating metformin in conjunction with SBRT for early-stage NSCLC.

Patients and methods: The trial evaluated patients with American Joint Commission on Cancer (AJCC) 7th edition Stage I-II, cT1-T2N0M0 NSCLC who were randomized 6:1 to receive metformin versus placebo in conjunction with SBRT. The outcomes analyzed included local failure …

Predicting Suicidality In Late-Life Depression By 3d Convolutional Neural Network And Cross-Sample Entropy Analysis Of Resting-State Fmri, Chemin Lin, Chih-Mao Huang, Wei Chang, You-Xun Chang, Ho-Ling Liu, Shu-Hang Ng, Huang-Li Lin, Tatia Mei-Chun Lee, Shwu-Hua Lee, Shun-Chi Wu

Faculty, Staff and Student Publications

Background: Predicting suicide is a pressing issue among older adults; however, predicting its risk is difficult. Capitalizing on the recent development of machine learning, considerable progress has been made in predicting complex behavior such as suicide. As depression remained the strongest risk for suicide, we aimed to apply deep learning algorithms to identify suicidality in a group with late-life depression (LLD).

Methods: We enrolled 83 patients with LLD, 35 of which were non-suicidal and 48 were suicidal, including 26 with only suicidal ideation and 22 with past suicide attempts, for resting-state functional magnetic resonance imaging (MRI). Cross-sample entropy (CSE) analysis …

A Reinforcement Learning (Rl)-Motivated Simulation Framework For Evaluating Vancomycin Dosing Strategies, Bingyu Mao, Ziqian Xie, Laila Rasmy, Masayuki Nigo, Degui Zhi

Faculty, Staff and Student Publications

Achieving and maintaining the therapeutic range in vancomycin treatment is important for optimal outcomes. While guidelines and best practices based on empirical studies exist, the theoretical best dosing strategies under various conditions remain illusive. We developed an RL-based simulation framework using a deep learning two-compartment pharmacokinetic model (PK-RNN-2CM) and introduced the area under the time-concentration curve (AUC) reward score, which translates clinical guidelines into an RL reward. Ground truth time-concentration curves were generated from patient-specific data, and simulated curves were produced under different dosing strategies with optional noise perturbations to mimic real-world settings. Evaluation metrics included 24-hour AUC assessments and …

Real-World Analysis Of Safety And Efficacy Of Car T-Cell Therapy In Lymphoma Patients With Decreased Kidney Function, Omar Mamlouk, Paolo Strati, Lei Feng, Ryan Sun, Amy Ayers, Raphael E Steiner, Ranjit Nair, Christopher Flowers, Jeremy L Ramdial, Neeraj Saini, Samer A Srour, Richard E Champlin, Partow Kebriaei, Loretta J Nastoupil, Maria A Rodriguez, Elizabeth J Shpall, Yago Nieto, Jason Westin, Sattva S Neelapu, Sreedhar Mandayam, Sairah Ahmed

Faculty, Staff and Student Publications

No abstract provided.

Microstructural Organization Of Distributed White Matter Associated With Fine Motor Control In Us Service Members With Mild Traumatic Brain Injury, Benjamin S C Wade, David F Tate, Eamonn Kennedy, Erin D Bigler, Gerald E York, Brian A Taylor, Maya Troyanskaya, Elizabeth S Hovenden, Naomi Goodrich-Hunsaker, Mary R Newsome, Emily L Dennis, Tracy Abildskov, Mary Jo Pugh, William C Walker, Kimbra Kenney, Aaron Betts, Robert Shih, Robert C Welsh, Elisabeth A Wilde

Faculty, Staff and Student Publications

Mild traumatic brain injury (mTBI) is the most common form of brain injury. While most individuals recover from mTBI, roughly 20% experience persistent symptoms, potentially including reduced fine motor control. We investigate relationships between regional white matter organization and subcortical volumes associated with performance on the Grooved Pegboard (GPB) test in a large cohort of military Service Members and Veterans (SM&Vs) with and without a history of mTBI(s). Participants were enrolled in the Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium. SM&Vs with a history of mTBI(s) (n = 847) and without mTBI (n = …

Refinement Of An Emergency Department-Based, Advance Care Planning Intervention For Patients With Cognitive Impairment And Their Caregivers, Kei Ouchi, Christopher Joshi, Jenson Kaithamattam, Seth A Gale, Gad A Marshall, Alison Pietras, Wei Wang, Edward W Boyer, James A Tulsky, Susan D Block, Dorene Rentz, Mara A Schonberg

Faculty, Staff and Student Publications

Background and objectives: Advance care planning (ACP) conversations are important to provide goal-concordant care (i.e., the care that matches the patient's previously stated goals) near end of life. While 31% of older adults presenting to the emergency department (ED) have dementia, only 39% have previously had ACP conversations. We refined and piloted an ED-based, motivational interview designed to stimulate ACP conversations (ED GOAL) for patients living with cognitive impairment and their caregivers.

Research design and methods: We systematically refined ED GOAL and then conducted an acceptability study in an urban, academic medical center. We prospectively enrolled adults aged 50+ with …