Life Sciences Commons^™

Natural History Models For Lung Cancer: A Scoping Review, Renu Sara Nargund, Sayaka Ishizawa, Maryam Eghbalizarch, Paul Yeh, Seyyed Mostafa Mousavi Janbeh Saray, Sara Nofal, Yimin Geng, Pianpian Cao, Edwin J Ostrin, Rafael Meza, Martin C Tammemägi, Robert J Volk, Maria A Lopez-Olivo, Iakovos Toumazis

Faculty, Staff and Student Publications

Introduction: Natural history models (NHMs) of lung cancer (LC) simulate the disease's natural progression providing a baseline for assessing the impact of interventions. NHMs have been increasingly used to inform public health policies, highlighting their utility. The objective of this scoping review was to summarize existing LC NHMs, identify their limitations, and propose a framework for future NHM development.

Methods: We searched MEDLINE, Embase, Web of Science, and IEEE Xplore from their inception to October 5, 2023, for peer-reviewed, full-length articles with an LC NHM. Model characteristics, their applications, data sources used, and limitations were extracted and narratively synthesized.

Results: …

Unveiling The Intercompartmental Signaling Axis: Mitochondrial To Er Stress Response (Mersr) And Its Impact On Proteostasis, Jeson J Li, Nan Xin, Chunxia Yang, Bo G Kim, Larissa A Tavizon, Ruth Hong, Jina Park, Travis I Moore, Rebecca George Tharyan, Adam Antebi, Hyun-Eui Kim

Faculty, Staff and Student Publications

Maintaining protein homeostasis is essential for cellular health. Our previous research uncovered a cross-compartmental Mitochondrial to Cytosolic Stress Response, activated by the perturbation of mitochondrial proteostasis, which ultimately results in the improvement of proteostasis in the cytosol. Here, we found that this signaling axis also influences the unfolded protein response of the endoplasmic reticulum (UPRER), suggesting the presence of a Mitochondria to ER Stress Response (MERSR). During MERSR, the IRE1 branch of UPRER is inhibited, introducing a previously unknown regulatory component of MCSR. Moreover, proteostasis is enhanced through the upregulation of the PERK-eIF2α signaling pathway, increasing phosphorylation of eIF2α and …

Ethical Concerns And Implications Of Expanded Carrier Screening, Emily Andres

Undergraduate Honors Capstone Projects

The rapid evolution in the field of genetics is often met with uncertainty and skepticism. With the advancements in genetic technologies, expanded carrier screening (ECS) has emerged as a powerful tool in reproductive medicine. Traditionally, carrier screening was provided less broadly, often relying on ethnic-based approaches. However, further advancements have deemed this practice no longer equitable or widely accepted. While ECS provides prospective parents with insight into their genetic risk and may prevent severe genetic conditions, it also raises serious ethical questions for many. These concerns span medical, political, and societal facets including medicalization, defining severity, abortion, legislation, insurability, the …

Defining The Optimal Radiation-Induced Lymphopenia Metric To Discern Its Survival Impact In Esophageal Cancer, Pim J J Damen, Max Peters, Brian Hobbs, Yiqing Chen, Uwe Titt, Remi Nout, Radhe Mohan, Steven H Lin, Peter S N Van Rossum

Faculty, Staff and Student Publications

Purpose: A detrimental association between radiation-induced lymphopenia (RIL) and oncologic outcomes in patients with esophageal cancer has been established. However, an optimal metric for RIL remains undefined but is important for the application of this knowledge in clinical decision-making and trial designs. The aim of this study was to find the optimal RIL metric discerning survival.

Methods and materials: Patients with esophageal cancer treated with concurrent chemoradiation therapy (CRT; 2004-2022) were selected. Studied metrics included absolute lymphocyte counts (ALCs) and neutrophil counts-and calculated derivatives-at baseline and during CRT. Multivariable Cox regression models for progression-free survival (PFS) and overall survival (OS) …

Comic: A Bayesian Dose Optimization Design For Drug Combination In Multiple Indications With Application To Car-T Therapies, Kai Chen, Kentaro Takeda, Ying Yuan

Faculty, Staff and Student Publications

Project Optimus, initiated by the US Food and Drug Administration (FDA), seeks to shift the focus of dose finding and selection from the maximum tolerated dose to the optimal dose that offers the most favorable risk-benefit balance. However, applying this paradigm shift to drug combination trials presents challenges, particularly due to limited sample sizes and a large two-dimensional dose exploration space. These challenges are amplified when trials involve multiple indications. To address this, we developed a two-stage Bayesian dose optimization design, called COMIC (Combination Optimization in Multiple IndiCations), to efficiently identify Optimal Biological Dose Combinations (OBDC) for multiple indications. The …

Health Impacts Of Remote Work On Women Aged 30-40: A Study Of Physical And Mental Well-Being, Dakota J. Miller

Doctoral Dissertations and Projects

The purpose of this phenomenological study is to understand the effects of remote work on employees' physical, psychological, and social well-being. As remote work becomes more common, understanding its impact on health and productivity is essential. This study asks: How does remote work affect employees’ well-being across these dimensions?

Guided by the Job Demands-Resources (JD-R) model (Bakker & Demerouti, 2007), this study examines how remote work influences well-being through the balance of job demands (e.g., workload, isolation) and resources (e.g., autonomy, flexibility).

Using a mixed-methods approach, data were collected from 22 remote workers via surveys, semi-structured interviews, and observations. Survey …

Novel Horticultural Approaches For Reduced Gravity And Controlled Environment Agriculture, Sarah Elizabeth Schreck

All Graduate Theses and Dissertations, Fall 2023 to Present

On July 16, 1969, Apollo 11 achieved the first successful moon landing, marking a significant milestone in human space exploration. This historic moment effectively ended the space race between the United States and the Soviet Union, and since then, countries around the world have continued to advance their space programs. While the space race has evolved, the next major challenge lies in sending humans to Mars—a journey that could take 6 to 9 months each way, presenting numerous challenges, including the critical issue of nutritional sustainment for the crew.

This thesis addresses key aspects of a broader effort to support …

Enhancing The Safety And Efficacy Of Cell Therapy With Programmed Sense-And-Respond Function, Andrew J Walters, Xiaoyu Yang, Scott D Olson, Caleb J Bashor

Faculty, Staff and Student Publications

No abstract provided.

Precision Proteogenomics Reveals Pan-Cancer Impact Of Germline Variants, Fernanda Martins Rodrigues, Nadezhda V Terekhanova, Kathleen J Imbach, Karl R Clauser, Myvizhi Esai Selvan, Isabel Mendizabal, Yifat Geffen, Yo Akiyama, Myranda Maynard, Tomer M Yaron, Yize Li, Song Cao, Erik P Storrs, Olivia S Gonda, Adrian Gaite-Reguero, Akshay Govindan, Emily A Kawaler, Matthew A Wyczalkowski, Robert J Klein, Berk Turhan, Karsten Krug, D R Mani, Felipe Da Veiga Leprevost, Alexey I Nesvizhskii, Steven A Carr, David Fenyö, Michael A Gillette, Antonio Colaprico, Antonio Iavarone, Ana I Robles, Kuan-Lin Huang, Chandan Kumar-Sinha, François Aguet, Alexander J Lazar, Lewis C Cantley, Urko M Marigorta, Zeynep H Gümüş, Matthew H Bailey, Gad Getz, Eduard Porta-Pardo, Li Ding

Faculty, Staff and Student Publications

We investigate the impact of germline variants on cancer patients' proteomes, encompassing 1,064 individuals across 10 cancer types. We introduced an approach, "precision peptidomics," mapping 337,469 coding germline variants onto peptides from patients' mass spectrometry data, revealing their potential impact on post-translational modifications, protein stability, allele-specific expression, and protein structure by leveraging the relevant protein databases. We identified rare pathogenic and common germline variants in cancer genes potentially affecting proteomic features, including variants altering protein abundance and structure and variants in kinases (ERBB2 and MAP2K2) impacting phosphorylation. Precision peptidome analysis predicted destabilizing events in signal-regulatory protein alpha (SIRPA) and glial …

The Roles Of Rnt1 And Putative Endoribonucleases In Eukaryotic Mrna Degradation, Lee-Ann Notice-Sarpaning

Dissertations and Theses (Open Access)

Endoribonucleases initiate degradation by cleaving RNAs internally. Mutations in these enzymes have been shown to cause diseases such as cancer, developmental disorders, and neurodegenerative diseases. Yet, eukaryotic endoribonucleases have not been well studied, especially with regard to their role in nuclear mRNA degradation. Rnt1 is a Saccharomyces cerevisiae (budding yeast) nuclear endoribonuclease and homolog of human Drosha with well-characterized roles in the processing of ncRNAs. The enzyme recognizes and cleaves double-stranded RNA stems containing a terminal tetraloop with an AGNN consensus sequence. However, the scope and consequence of its function in mRNA degradation has heretofore been unclear. Previous studies have …

A Comparison Of Carbon Ions Versus Protons For Integrated Mode Ion Imaging, Mikaël Simard, Ryan Fullarton, Lennart Volz, Christoph Schuy, Daniel G Robertson, Allison Toltz, Colin Baker, Sam Beddar, Christian Graeff, Charles-Antoine Collins Fekete

Faculty, Staff and Student Publications

Background: Incorporating image guidance into ion beam therapy is critical for minimizing beam range uncertainties and realizing the modality's potential. One promising avenue for image guidance is to capture transmission ion radiographs (iRads) before and/or during treatment. iRad image quality is typically maximized using a single-event imaging system, which involves tracking individual ions, albeit the approach is generally not suited to clinical beam settings. An alternative faster and clinically compatible method is integrated mode imaging, where individual pencil beam data is acquired, rather than single ion data. To evaluate the usefulness of transmission ion imaging for image guidance, it is …

Impact Of Comorbidities On The Mortality Benefits Of Lung Cancer Screening: A Post-Hoc Analysis Of The Plco And Nlst Trials, Sebastien Gendarme, Ehsan Irajizad, James P Long, Johannes F Fahrmann, Jennifer B Dennison, Seyyed Mahmood Ghasemi, Rongzhang Dou, Robert J Volk, Rafael Meza, Iakovos Toumazis, Florence Canoui-Poitrine, Samir M Hanash, Edwin J Ostrin

Faculty, Staff and Student Publications

Objectives: To evaluate how comorbidities affect mortality benefits of lung cancer screening (LCS) with low-dose computed tomography.

Methods: We developed a comorbidity index (Prostate, Lung, Colorectal, and Ovarian comorbidity index [PLCO-ci]) using LCS-eligible participants' data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) trial (training set) and the National Lung Screening Trial (NLST) (validation set). PLCO-ci predicts five-year non-lung cancer (LC) mortality using a regularized Cox model; with performance evaluated using the area under the receiver operating characteristics curve. In NLST, LC mortality (per original publication) was compared between low-dose computed tomography and chest radiograph arms across the PLCO-ci quintile …

The Contribution Of De Novo Coding Mutations To Meningomyelocele, Yoo-Jin Jiny Ha, Ashna Nisal, Isaac Tang, Chanjae Lee, Ishani Jhamb, Cassidy Wallace, Robyn Howarth, Sarah Schroeder, Keng Ioi Vong, Naomi Meave, Fiza Jiwani, Chelsea Barrows, Sangmoon Lee, Nan Jiang, Arzoo Patel, Krisha Bagga, Niyati Banka, Liana Friedman, Francisco A Blanco, Seyoung Yu, Soeun Rhee, Hui Su Jeong, Isaac Plutzer, Michael B Major, Béatrice Benoit, Christian Poüs, Caleb Heffner, Zoha Kibar, Gyang Markus Bot, Hope Northrup, Kit Sing Au, Madison Strain, Allison E Ashley-Koch, Richard H Finnell, Joan T Le, Hal S Meltzer, Camila Araujo, Helio R Machado, Roger E Stevenson, Anna Yurrita, Sara Mumtaz, Awais Ahmed, Mulazim Hussain Khara, Osvaldo M Mutchinick, José Ramón Medina-Bereciartu, Friedhelm Hildebrandt, Gia Melikishvili, Ahmed I Marwan, Valeria Capra, Mahmoud M Noureldeen, Aida M S Salem, Mahmoud Y Issa, Maha S Zaki, Libin Xu, Ji Eun Lee, Donghyuk Shin, Anna Alkelai, Alan R Shuldiner, Stephen F Kingsmore, Stephen A Murray, Heon Yung Gee, W Todd Miller, Kimberley F Tolias, John B Wallingford, Spina Bifida Sequencing Consortium, Sangwoo Kim, Joseph G Gleeson

Faculty, Staff and Students Publications

Meningomyelocele (also known as spina bifida) is considered to be a genetically complex disease resulting from a failure of the neural tube to close. Individuals with meningomyelocele display neuromotor disability and frequent hydrocephalus, requiring ventricular shunting. A few genes have been proposed to contribute to disease susceptibility, but beyond that it remains unexplained1. We postulated that de novo mutations under purifying selection contribute to the risk of developing meningomyelocele2. Here we recruited a cohort of 851 meningomyelocele trios who required shunting at birth and 732 control trios, and found that de novo likely gene disruption or …

Air Embolism After Percutaneous Lung Biopsy Or Ablation: A Report Of Six Cases, Rebecca Choi, Haylie Kieu-Mi Phan, Varshana Gurusamy, Rahul A Sheth, Bruno C Odisio, Kelvin Hong, Alda L Tam

Faculty, Staff and Student Publications

Systemic air embolism is a rare but potentially life-threatening complication of percutaneous lung biopsy and ablation. This report describes six patients (four male, two female) with air embolism following CT-guided lung interventions at two institutions between January 2021 and March 2024. Air embolisms were identified in locations such as the pulmonary vein, left ventricle, and coronary arteries, with clinical presentations ranging from asymptomatic to life-threatening events. Prompt intervention, including oxygen therapy, patient repositioning, and intravenous administration of epinephrine in cases of cardiac arrest, resulted in favorable outcomes. This series highlights the importance of early detection of systemic air embolism and …

Race And Clinical Outcomes In Hormone Receptor-Positive, Her2-Negative, Node-Positive Breast Cancer In The Randomized Rxponder Trial, Yara Abdou, William E Barlow, Julie R Gralow, Funda Meric-Bernstam, Kathy S Albain, Daniel F Hayes, Nancy U Lin, Edith A Perez, Lori J Goldstein, Stephen K L Chia, Sukhbinder Dhesy-Thind, Priya Rastogi, Emilio Alba, Suzette Delaloge, Anne F Schott, Steven Shak, Priyanka Sharma, Danika L Lew, Jieling Miao, Joseph M Unger, Debasish Tripathy, Gabriel N Hortobagyi, Lajos Pusztai, Kevin Kalinsky

Faculty, Staff and Student Publications

Background: The phase III RxPONDER trial has affected treatment for node-positive (1-3), hormone receptor-positive, HER2-negative breast cancer with a 21-gene recurrence score (RS) less than 26. We investigated how these findings apply to different racial and ethnic groups within the trial.

Methods: The trial randomly assigned women to endocrine therapy (ET) or to chemotherapy plus ET. The primary clinical outcome was invasive disease-free survival (IDFS), with distant relapse-free survival (DRFS) as a secondary outcome. Multivariable Cox models were used to evaluate the association between race/ethnicity and survival outcomes, adjusting for clinicopathological characteristics, RS, and treatment.

Results: A total of 4048 …

Rna Sculpting By The Primordial Helix-Clasp-Helix-Strand-Loop (Hch-Sl) Motif Enforces Chemical Recognition Enabling Diverse Kh Domain Functions, John A Tainer, Susan E Tsutakawa

Faculty, Staff and Student Publications

In all domains of life, the ancient K homology (KH) domain superfamily is central to RNA processes including splicing, transcription, posttranscriptional gene regulation, signaling, and translation. Proteins with 1 to 15 KH domains bind single-strand (ss) RNA or DNA with base sequence specificity. Here, we examine over 40 KH domain experimental structures in complex with nucleic acid (NA) and define a novel Helix-clasp-Helix-Strand-Loop (HcH-SL) NA recognition motif binding 4 to 5 nucleotides using 10 to 18 residues. HcH-SL includes and extends the Gly-X-X-Gly (GXXG) signature sequence "clasp" that brings together two helices as an ∼90° helical corner. The first helix …

Justification, Margin Values, And Analysis Populations For Oncologic Noninferiority And Equivalence Trials: A Meta-Epidemiological Study, Troy J Kleber, Alexander D Sherry, Andrew J Arifin, Gabrielle S Kupferman, Ramez Kouzy, Joseph Abi Jaoude, Timothy A Lin, Esther J Beck, Avital M Miller, Adina H Passy, Zachary R Mccaw, Pavlos Msaouel, Ethan B Ludmir

Faculty, Staff and Student Publications

Background: Noninferiority and equivalence trials evaluate whether an experimental therapy's effect on the primary endpoint is contained within an acceptable margin compared with standard of care. The reliability and impact of this conclusion, however, is largely dependent on the justification for this design, the choice of margin, and the analysis population used.

Methods: A meta-epidemiological study was performed of phase 3 randomized noninferiority and equivalence oncologic trials registered at ClinicalTrials.gov. Data were extracted from each trial's registration page and primary manuscript.

Results: We identified 65 noninferiority and 10 equivalence trials that collectively enrolled 61 632 patients. Of these, 61 (81%) …

Donor Age Matters For Haploidentical Hct Patients Even After Adjusting For Hla Factors: A Machine Learning Approach, Rohtesh S Mehta, Rodney Sparapani, Tao Wang, Stephen Spellman, Stephanie J Lee, Effie W Petersdorf

Faculty, Staff and Student Publications

No abstract provided.

Pharmacotherapy And Non-Invasive Neuromodulation For Neuropathic Pain: A Systematic Review And Meta-Analysis, Nadia Soliman, Xavier Moisset, Michael C Ferraro, Daniel Ciampi De Andrade, Ralf Baron, Joletta Belton, David L H Bennett, Margarita Calvo, Patrick Dougherty, Ian Gilron, Aki J Hietaharju, Koichi Hosomi, Peter R Kamerman, Harriet Kemp, Elena K Enax-Krumova, Ewan Mcnicol, Theodore J Price, Srinivasa N Raja, Andrew S C Rice, Blair H Smith, Fiona Talkington, Andrea Truini, Jan Vollert, Nadine Attal, Nanna B Finnerup, Simon Haroutounian

Faculty, Staff and Student Publications

Background: There remains a substantial unmet need for effective and safe treatments for neuropathic pain. The Neuropathic Pain Special Interest Group aimed to update treatment recommendations, published in 2015, on the basis of new evidence from randomised controlled trials, emerging neuromodulation techniques, and advances in evidence synthesis.

Methods: For this systematic review and meta-analysis, we searched Embase, PubMed, the International Clinical Trials Registry, and ClinicalTrials.gov from data inception for neuromodulation trials and from Jan 1, 2013, for pharmacological interventions until Feb 12, 2024. We included double-blind, randomised, placebo-controlled trials that evaluated pharmacological and neuromodulation treatments administered for at least 3 …

Temporal Trends Of Subsequent Central Nervous System Malignancies Among Survivors Of Childhood Cancer, Robert T Galvin, Yan Chen, Yan Yuan, Tabitha Cooney, Rebecca Howell, Susan Smith, Michael A Arnold, Miriam Conces, Wendy Leisenring, Gregory T Armstrong, Joseph P Neglia, Lucie M Turcotte

Faculty, Staff and Student Publications

Background: It is not known whether temporal changes in childhood cancer therapy have reduced risk of subsequent malignant neoplasms of the central nervous system (CNS), a frequently fatal late effect of cancer therapy.

Methods: Five-year survivors of primary childhood cancers diagnosed between 1970 and 1999 in the Childhood Cancer Survivor Study with CNS subsequent malignant neoplasms were identified. Cumulative incidence rates and standardized incidence ratios were compared among survivors diagnosed between 1970-1979 (n = 6223), 1980-1989 (n = 9680), and 1990-1999 (n = 8999). Multivariable models assessed risk factors for CNS subsequent malignant neoplasms.

Results: A total of 157 CNS …

Unveiling The Intercompartmental Signaling Axis: Mitochondrial To Er Stress Response (Mersr) And Its Impact On Proteostasis, Jeson J Li, Nan Xin, Chunxia Yang, Bo G Kim, Larissa A Tavizon, Ruth Hong, Jina Park, Travis I Moore, Rebecca George Tharyan, Adam Antebi, Hyun-Eui Kim

Faculty, Staff and Student Publications

Maintaining protein homeostasis is essential for cellular health. Our previous research uncovered a cross-compartmental Mitochondrial to Cytosolic Stress Response, activated by the perturbation of mitochondrial proteostasis, which ultimately results in the improvement of proteostasis in the cytosol. Here, we found that this signaling axis also influences the unfolded protein response of the endoplasmic reticulum (UPRER), suggesting the presence of a Mitochondria to ER Stress Response (MERSR). During MERSR, the IRE1 branch of UPRER is inhibited, introducing a previously unknown regulatory component of MCSR. Moreover, proteostasis is enhanced through the upregulation of the PERK-eIF2α signaling pathway, increasing phosphorylation of eIF2α and …

Sustained Improvement In Health-Related Quality Of Life In Transplant-Ineligible Newly Diagnosed Multiple Myeloma Treated With Daratumumab, Lenalidomide, And Dexamethasone: Maia Final Analysis Of Patient-Reported Outcomes, Aurore Perrot, Thierry Facon, Torben Plesner, Saad Z Usmani, Shaji Kumar, Nizar J Bahlis, Cyrille Hulin, Robert Z Orlowski, Hareth Nahi, Peter Mollee, Karthik Ramasamy, Murielle Roussel, Arnaud Jaccard, Michel Delforge, Lionel Karlin, Bertrand Arnulf, Ajai Chari, George Wang, Niodita Gupta-Werner, Shuchita Kaila, Huiling Pei, Kathryn Matt, Katharine S Gries, Robin Carson, Fredrik Borgsten, Katja Weisel

Faculty, Staff and Student Publications

Objectives: This final post hoc analysis evaluated patient-reported outcomes from the Phase 3 MAIA study of daratumumab, lenalidomide, and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) after median 64.5-month follow-up in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM), including patient subgroups.

Methods: Key scales from the EORTC QLQ-C30 (global health status [GHS], physical functioning, pain, and fatigue) were assessed. Scores were evaluated every 3 months for 1 year, then every 6 months until disease progression.

Results: The intent-to-treat population (n = 737) included 46.3% frail, 35.4% 70 to < 75 years old, and 43.6% ≥ 75 years old. D-Rd-treated patients showed improvements from baseline that were sustained over 5 years in the intent-to-treat population and across subgroups by age, frailty, and bone lesions. Greater proportions of patients treated with D-Rd versus Rd achieved minimally important changes for improvement at cycle 36 (year ~3) in GHS (odds ratio, 1.84 [95% CI, 1.16-2.91]), physical functioning (1.93 [1.18-3.14]), pain (1.41 [0.90-2.22]), and fatigue (2.00 [1.24-3.23]). Greater proportions of patients with bone lesions improved with D-Rd versus Rd on GHS and physical functioning.

Conclusions: In transplant-ineligible patients with NDMM, D-Rd improved health-related quality of …

Multiparametric Mri Scoring System Of The Pancreas For The Diagnosis Of Chronic Pancreatitis, Temel Tirkes, Dhiraj Yadav, Darwin L Conwell, Xuandong Zhao, Anil K Dasyam, Vivek Gowdra Halappa, Aashish Patel, Zarine K Shah, Jordan Swensson, Naoki Takahashi, Sudhakar Venkatesh, Ashley Wachsman, Liang Li, Kristofer Jennings, Yunlong Yang, Phil A Hart, Stephen J Pandol, Walter G Park, Santhi Swaroop Vege, Mark Topazian, Paul R Territo, Scott A Persohn, Dana K Andersen, Evan L Fogel, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Student Publications

Background: Ductal features alone may not offer high diagnostic sensitivity or most accurate disease severity of chronic pancreatitis (CP).

Purpose: Diagnose CP based on multiparametric MRI and MRCP features.

Study type: Prospective.

Population: Between February 2019 and May 2021, 46 control (23 males, 49.3 ± 14.1 years), 45 suspected (20 males, 48.7 ± 12.5 years), and 46 definite (20 males, 53.7 ± 14.6 years) CP patients were enrolled at seven hospitals enrolled in the MINIMAP study. CP classification was based on imaging findings and clinical presentation.

Field strength and sequences: 1.5 T. T1-weighted (T1W) spoiled gradient echo, T1 map with …

Deciphering The Longitudinal Trajectories Of Glioblastoma Ecosystems By Integrative Single-Cell Genomics, Avishay Spitzer, Kevin C Johnson, Masashi Nomura, Luciano Garofano, Djamel Nehar-Belaid, Noam Galili Darnell, Alissa C Greenwald, Lillian Bussema, Young Taek Oh, Frederick S Varn, Fulvio D'Angelo, Simon Gritsch, Kevin J Anderson, Simona Migliozzi, L Nicolas Gonzalez Castro, Tamrin Chowdhury, Nicolas Robine, Catherine Reeves, Jong Bae Park, Anuja Lipsa, Frank Hertel, Anna Golebiewska, Simone P Niclou, Labeeba Nusrat, Sorcha Kellet, Sunit Das, Hyo-Eun Moon, Sun Ha Paek, Franck Bielle, Alice Laurenge, Anna Luisa Di Stefano, Bertrand Mathon, Alberto Picca, Marc Sanson, Shota Tanaka, Nobuhito Saito, David M Ashley, Stephen T Keir, Keith L Ligon, Jason T Huse, W K Alfred Yung, Anna Lasorella, Antonio Iavarone, Roel G W Verhaak, Itay Tirosh, Mario L Suvà

Faculty, Staff and Student Publications

The evolution of isocitrate dehydrogenase (IDH)-wildtype glioblastoma (GBM) after standard-of-care therapy remains poorly understood. Here we analyzed matched primary and recurrent GBMs from 59 patients using single-nucleus RNA sequencing and bulk DNA sequencing, assessing the longitudinal evolution of the GBM ecosystem across layers of cellular and molecular heterogeneity. The most consistent change was a lower malignant cell fraction at recurrence and a reciprocal increase in glial and neuronal cell types in the tumor microenvironment (TME). The predominant malignant cell state differed between most matched pairs, but no states were exclusive or highly enriched in either time point, nor was there …

Summary Of Research: Efficacy Of Trastuzumab Deruxtecan In Her2-Expressing Solid Tumors By Enrollment Her2 Ihc Status: Post Hoc Analysis Of Destiny-Pantumor02, Ana Oaknin, Jung-Yun Lee, Vicky Makker, Do-Youn Oh, Susana Banerjee, Antonio González-Martín, Kyung Hae Jung, Iwona Ługowska, Luis Manso, Aránzazu Manzano, Bohuslav Melichar, Salvatore Siena, Daniil Stroyakovskiy, Anitra Fielding, Soham Puvvada, Ann Smith, Funda Meric-Bernstam

Faculty, Staff and Student Publications

of the original article, 'Efficacy of Trastuzumab Deruxtecan in HER2-Expressing Solid Tumors by Enrollment HER2 IHC Status: Post Hoc Analysis of DESTINY-PanTumor02'. Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate, which is a chemotherapy with a linker (deruxtecan) joined to an antibody (trastuzumab). Trastuzumab binds to the human epidermal growth factor receptor 2 (HER2) protein on cancer cells, where it releases the chemotherapy to kill these cells. The DESTINY-PanTumor02 clinical study tested the effectiveness of T-DXd for people with various HER2-expressing cancers and the safety of treatment. Previous results from DESTINY-PanTumor02 showed that T-DXd had antitumor activity, and the greatest effects …

Gene Promoters Are Genomically Encoded To Facilitate Histone Exchange/Incorporation, Blaine Bartholomew

Faculty, Staff and Student Publications

Gene promoters are intrinsically hardwired not only to facilitate transcription preinitiation complex formation but also the release of paused RNA polymerase by H2A.Z. A new PLOS Biology study reveals poly (dA) tracts at promoters positively stimulate H2A.Z incorporation by the SWR complex in yeast.

Using A Surgical Risk Predictor To Estimate Percutaneous Cryoablation Adverse Event Risk: A Single Center Comparative Analysis, Prisha Patel, Koustav Pal, Hadi Ahmed, Bill Tang, Iwan Paolucci, Mohammad Khavandi, Peiman Habibollahi, Ketan Shah, Steven Y Huang, Bruno C Odisio, Sanjay Gupta, Kamran Ahrar, Steven Yevich, Joshua D Kuban, Alda Tam, Rahul A Sheth

Faculty, Staff and Student Publications

Objective: To evaluate the relevance of established surgical risk calculators for predicting complications in patients undergoing percutaneous lung cryoablation (PLC).

Methods: The institution's database was queried for PLC procedures from March 2015 to May 2024, excluding those patients with concomitant local therapies or five or more lesions treated in a single setting. Demographics, frailty metrics as defined by the surgical literature, and procedural variables were collected. To evaluate the suitability of surgical risk estimate calculators, the requisite demographic data were input into the American College of Surgery surgical risk calculator; estimates for length of stay (LOS), serious complications, 30-day readmission, …

Dose Prediction Via Deep Learning To Enhance Treatment Planning Of Lung Radiotherapy Including Simultaneous Integrated Boost Techniques, Wenhua Cao, Mary Gronberg, Stephen Bilton, Hana Baroudi, Skylar Gay, Christopher Peeler, Zhongxing Liao, Thomas J Whitaker, Karen Hoffman, Laurence E Court

Faculty, Staff and Student Publications

Background: Recent studies have shown deep learning techniques are able to predict three-dimensional (3D) dose distributions of radiotherapy treatment plans. However, their use in dose prediction for treatments with varied prescription doses including simultaneous integrated boost (SIB), that is, using multiple prescription doses within the same plan, and benefit in improving plan quality should be validated.

Purpose: To investigate the feasibility and potential benefit of using deep learning to predict dose distribution of volumetric modulated arc therapy (VMAT) including SIB techniques and improve treatment planning for patients with lung cancer.

Methods: The dose prediction model was trained with 93 retrospective …

Tumoral And Circulating Genomic Landscape Inform Survival Differences In Colorectal Carcinomatosis, Michael G White, Reed I Ayabe, Mohammad A Zeineddine, Fadl A Zeineddine, Abdelrahman M G Yousef, Mahmoud Yousef, Norman J Galbraith, J Bryan Iorgulescu, Christopher Scally, Keith Fournier, Timothy E Newhook, Nancy Y You, Jason Willis, Scott Kopetz, George J Chang, John Paul Shen, Abhineet Uppal

Faculty, Staff and Student Publications

Colorectal peritoneal metastases (CPM) are the third most common site of metastatic spread of colorectal cancer and are associated with worse survival than other sites of metastatic disease. In recent years tumoral circulating tumoral DNA (ctDNA) mutational status has been increasingly utilized in clinical decision making for metastatic colorectal cancer patients despite its utility in CPM being poorly understood. Here we describe standard of care performed mutational profiles and associated outcomes for unresectable CPM patients, with a contextual comparison to 160 unresected colorectal liver metastases (CLM) patients. Of 508 patients, 288 (57 %) had CPM alone and 220 (43 %) …

Oculomics: Current Concepts And Evidence, Zhuoting Zhu, Yueye Wang, Ziyi Qi, Wenyi Hu, Xiayin Zhang, Siegfried K Wagner, Yujie Wang, An Ran Ran, Joshua Ong, Ethan Waisberg, Mouayad Masalkhi, Alex Suh, Yih Chung Tham, Carol Y Cheung, Xiaohong Yang, Honghua Yu, Zongyuan Ge, Wei Wang, Bin Sheng, Yun Liu, Andrew G Lee, Alastair K Denniston, Peter Van Wijngaarden, Pearse A Keane, Ching-Yu Cheng, Mingguang He, Tien Yin Wong

Faculty, Staff and Student Publications

The eye provides novel insights into general health, as well as pathogenesis and development of systemic diseases. In the past decade, growing evidence has demonstrated that the eye's structure and function mirror multiple systemic health conditions, especially in cardiovascular diseases, neurodegenerative disorders, and kidney impairments. This has given rise to the field of oculomics-the application of ophthalmic biomarkers to understand mechanisms, detect and predict disease. The development of this field has been accelerated by three major advances: 1) the availability and widespread clinical adoption of high-resolution and non-invasive ophthalmic imaging ("hardware"); 2) the availability of large studies to interrogate associations …