Biomedical Informatics Commons^™

Evaluation Of A Comprehensive Set Of Normal Tissue Complication Probability Models For Patients With Head And Neck Cancer In An International Cohort, Suzanne P M De Vette, Maria I Van Rijn-Dekker, Lisa Van Den Bosch, Kylie Keijzer, Hendrike Neh, Hung Chu, Yan Li, Mark L Frederiks, Hans Paul Van Der Laan, Jolien Heukelom, Peter Van Luijk, Arjen Van Der Schaaf, Roel J H M Steenbakkers, Nanna M Sijtsema, Katherine A Hutcheson, Clifton D Fuller, Johannes A Langendijk, Amy C Moreno, Lisanne V Van Dijk

Faculty, Staff and Student Publications

Background/purpose: Normal tissue complication probability (NTCP) models can be used to guide radiation therapy (RT) decisions by estimating side-effect risks pretreatment to minimize (late) side-effects. Recently, a comprehensive individual toxicity risk (CITOR) profile of NTCP models addressing common side-effects in head and neck cancer (HNC) patients was developed. This study investigates the generalizability of these models in an international setting, with different treatment approaches and side-effect assessments, promoting their integration into more widespread clinical practice.

Materials/methods: From a prospective registry study, 407 HNC patients were included who were treated with definitive RT with or without systemic therapy between 2015 and …

Cytokine Storms In Covid-19, Hemophagocytic Lymphohistiocytosis, And Car-T Therapy, James P Long, Rishab Prakash, Paul Edelkamp, Mark Knafl, Anath C Lionel, Ranjit Nair, Sairah Ahmed, Paolo Strati, Luis E Malpica Castillo, Ajlan Al-Zaki, Kelly Chien, Dai Chihara, Jason Westin, Fareed Khawaja, Loretta J Nastoupil, Victor Mulanovich, Andrew Futreal, Scott E Woodman, Naval G Daver, Christopher R Flowers, Sattva Neelapu, Joanna-Grace Manzano, Swaminathan P Iyer

Faculty, Staff and Student Publications

Importance: Cytokine storm (CS) is a hyperinflammatory syndrome causing multiorgan dysfunction and high mortality, especially in patients with malignant hematologic neoplasms. Triggers include malignant neoplasm-associated hemophagocytic lymphohistiocytosis (MN-HLH), cytokine release syndrome from chimeric antigen receptor T-cell therapy (CAR-T CRS), and COVID-19, but the underlying mechanisms of inflammation and their impact on outcomes are poorly understood.

Objective: To delineate the inflammatory patterns characterizing different CS etiologies and their association with clinical outcomes.

Design, setting, and participants: This retrospective cohort study was conducted at the MD Anderson Cancer Center in Houston, Texas, between March 1, 2020, and November 20, 2022, using the …

Circulating Short-Chain And Branched Short-Chain Fatty Acids And The Risk Of Incident Type 2 Diabetes: Findings From The 4c Study, Shuangyuan Wang, Hong Lin, Xiaojing Jia, Yiting Lin, Chunyan Hu, Mian Li, Yu Xu, Min Xu, Jie Zheng, Xinjie Zhao, Yanli Li, Lulu Chen, Tianshu Zeng, Ruying Hu, Zhen Ye, Lixin Shi, Qing Su, Yuhong Chen, Xuefeng Yu, Li Yan, Tiange Wang, Zhiyun Zhao, Guijun Qin, Qin Wan, Gang Chen, Meng Dai, Di Zhang, Bihan Qiu, Xiaoyan Zhu, Ruixin Liu, Xiao Wang, Xulei Tang, Zhengnan Gao, Feixia Shen, Xuejiang Gu, Zuojie Luo, Yingfen Qin, Li Chen, Xinguo Hou, Yanan Huo, Qiang Li, Guixia Wang, Yinfei Zhang, Chao Liu, Youmin Wang, Shengli Wu, Tao Yang, Huacong Deng, Jiajun Zhao, Yiming Mu, Guowang Xu, Shenghan Lai, Donghui Li, Guang Ning, Weiqing Wang, Yufang Bi, Jieli Lu

Faculty, Staff and Student Publications

Previous studies suggested that fecal short-chain fatty acids (SCFAs) and branched short-chain fatty acids (BCFAs) are associated with glucose regulation. However, the potential relationship between circulating SCFAs and BCFAs with incident diabetes risk in both men and women remains unidentified in prospective cohort studies. In this study, we examined a panel of nine serum SCFAs and BCFAs in 3414 subjects with incident diabetes, and matched normoglycemic controls from the China Cardiometabolic Disease and Cancer Cohort study. In fully adjusted conditional logistic regression models, total SCFAs, total BCFAs, and isovaleric acid were significantly associated with incident type 2 diabetes mellitus (T2DM) …

A Plain Language Summary Of The Ascertain Trial: Oral Decitabine And Cedazuridine Versus Intravenous Decitabine For Mds Or Cmml, Guillermo Garcia-Manero, James Mccloskey, Elizabeth A Griffiths, Karen W L Yee, Amer M Zeidan, Aref Al-Kali, H Joachim Deeg, Mitchell Sabloff, Mary-Margaret Keating, Nancy Zhu, Nashat Y Gabrail, Salman Fazal, Joseph Maly, Olatoyosi Odenike, Amy E Dezern, Casey L O'Connell, Gail J Roboz, Lambert Busque, Rena Buckstein, Harshad Amin, Brian Leber, Aditi Shastri, Aram Oganesian, Harold N Keer, Mohammad Azab, Michael R Savona

Faculty, Staff and Student Publications

What is this summary about?This summary describes results from a phase 3 clinical trial called ASCERTAIN.Researchers compared two treatments in people with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML), either of which can develop into acute myeloid leukemia (AML). One group was treated with oral decitabine and cedazuridine (oral DEC-C) and the other with intravenous decitabine.Treatment was given in a series of cycles. In the first cycle, people were randomly assigned to receive oral DEC-C or intravenous decitabine and then switched to the other treatment in the second cycle. After the first two cycles, everyone …

Real-World Effectiveness Of Chemoimmunotherapy And Novel Therapies For Patients With Relapsed/Refractory Aggressive Large B-Cell Lymphoma, Loretta J Nastoupil, Clark R Andersen, Amy Ayers, Yucai Wang, Thomas M Habermann, Dai Chihara, Brad S Kahl, Brian K Link, Jean L Koff, Jonathon B Cohen, Peter Martin, Izidore S Lossos, Michele Stanchina, Sara Haddadi, Carla Casulo, Sabarish Ayyappan, Ruitao Lin, Ziyi Li, Melissa A Larson, Matthew J Maurer, Lynn Huynh, Chi Gao, Ramya Ramasubramanian, Mei Sheng Duh, Alex Mutebi, Tongsheng Wang, Monika Jun, Anthony Wang, Rajesh Kamalakar, Anupama Kalsekar, James R Cerhan, Christopher R Flowers

Faculty, Staff and Student Publications

Introduction: Clinical trials provide meaningful data regarding the safety and efficacy of novel therapies but there is often a lag between the time of new drug approval and information on posttreatment clinical outcomes in real-world practice. This study evaluated clinical outcomes in a large real-world population of patients with relapsed and/or refractory large B-cell lymphoma (r/r LBCL) treated with chemoimmunotherapy or novel therapies in second or later lines of therapy (2L+).

Materials and methods: Data from the Lymphoma Epidemiology of Outcomes (LEO) Consortium of Real-World Evidence (CReWE) cohort (1/1/2015-2/15/2023) were analyzed. Patients' demographic and clinical characteristics were described and response …

Guidelines For The Management Of Pancreatic Cystic Lesions: Many Options, Too Few Solutions?, Yifan Wang, Michael P Kim

Faculty, Staff and Student Publications

No abstract provided.

Uncertainty-Guided Pancreatic Tumor Auto-Segmentation With Tversky Ensemble, Cenji Yu, Skylar S Gay, Aashish C Gupta, Rachael M Martin-Paulpeter, Ethan B Ludmir, Yao Zhao, Jack Duryea, Xinru Chen, Carlos E Cardenas, Jinzhong Yang, Albert C Koong, Tucker J Netherton, Dong Joo Rhee, Laurence E Court

Faculty, Staff and Student Publications

Background and purpose: Pancreatic gross tumor volume (GTV) delineation is challenging due to their variable morphology and uncertain ground truth. Previous deep learning-based auto-segmentation methods have struggled to handle tasks with uncertain ground truth and have not accommodated stylistic customizations. We aim to develop a human-in-the-loop pancreatic GTV segmentation tool using Tversky ensembles by leveraging uncertainty estimation techniques.

Material and methods: In this study, we utilized a total of 282 patients from the pancreas task of the Medical Segmentation Decathlon. Thirty patients were randomly selected to form an independent test set, while the remaining 252 patients were divided into an …

Age-Associated Proteins Explain The Role Of Medial Temporal Lobe Networks In Alzheimer’S Disease, Adam Turnbull, Yejin Kim, Kai Zhang, Xiaoqian Jiang, Zihuai He, Victor W Henderson, F Vankee Lin

Faculty, Staff and Student Publications

The structural connectivity (SC) of the medial temporal lobe and its associated cortical anterior temporal and posterior medial networks (MTL-AT-PM) is linked to pathologies and memory decline in Alzheimer's disease (AD). However, neuroimaging analyses cannot tell us how SC changes occur in AD at the molecular level and do not provide a means of intervening to slow/prevent pathology-related changes in MTL-AT-PM SC. The current study aimed to understand how and where AD-related changes occur within MTL-AT-PM using proteomics. We used a 4-step approach in 101 older adults from a local sample, aiming to understand how proteins and SC in combination …

Manual Therapy For Fibrosis-Related Late Effect Dysphagia In Head And Neck Cancer Survivors: The Mantle Nonrandomized Clinical Trial, Holly Mcmillan, Carla L Warneke, Sheila Buoy, Christine Porsche, Kiara Savage, Stephen Y Lai, Clifton D Fuller, Katherine A Hutcheson

Faculty, Staff and Student Publications

Importance: Late radiation-associated dysphagia (RAD) after head and neck cancer (HNC) treatment is challenging and commonly treatment refractory, with fibrosis stiffening connective tissues and compressing peripheral nerve tracts, contributing to diminished strength and possibly denervation of swallowing muscles. Manual therapy (MT), while common for cancer-related pain and other indications, remains largely unstudied for fibrosis-related late RAD.

Objective: To determine the feasibility and safety of MT, estimate effect size and durability of MT for associated improvements in cervical range of motion (CROM), and examine functional outcomes after MT in survivors of HNC with fibrosis-related late RAD.

Design, setting, and participants: This …

Correction To: Selinexor In Combination With Carboplatin And Paclitaxel In Patients With Advanced Solid Tumors: Results Of A Single-Center, Multi-Arm Phase Ib Study, Kyaw Z Thein, Daniel D Karp, Apostolia Tsimberidou, Jing Gong, Selma Sulovic, Jatin Shah, Denái R Milton, David S Hong, Filip Janku, Lacey Mcquinn, Bettzy A Stephen, Rivka Colen, Brett W Carter, Timothy A Yap, Sarina A Piha-Paul, Siqing Fu, Funda Meric-Bernstam, Aung Naing

Faculty, Staff and Student Publications

No abstract provided.

Self-Reported Cognitive Function In Older Breast Cancer Survivors After Chemotherapy Treatment, Rachel Kim, Julia Peña, Kai-Ping Liao, Susan K Peterson, Liang Li, Daria Zorzi, Holly M Holmes, Mariana Chavez-Macgregor, Sharon H Giordano

Faculty, Staff and Student Publications

Purpose: This study evaluated self-reported cognitive function in older breast cancer survivors and its association with prior chemotherapy.

Materials and methods: Breast cancer survivors aged 65-years and older, diagnosed 2012-2013, with local and regional stage disease, were identified through the linked Texas Cancer Registry-Medicare dataset. Survivors completed the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-CogV3) instrument and provided demographic and clinical data. A PCI--sub-score of less than 54 was used to identify cognitive impairment. Linear regression models were used to examine the FACT-CogV3 primary score, and logistic regression models evaluated the PCI--sub-score.

Results: Of 4448 eligible survivors, 1594 (35.8 %) …

Long Term Results Of Venetoclax Combined With Flag-Ida Induction And Consolidation For Newly Diagnosed And Relapsed Or Refractory Acute Myeloid Leukemia, Courtney D Dinardo, Wei-Ying Jen, Koichi Takahashi, Tapan M Kadia, Sanam Loghavi, Naval G Daver, Lianchun Xiao, Patrick K Reville, Ghayas C Issa, Nicholas J Short, Koji Sasaki, Sa A Wang, Jillian K Mullin, Sherry Pierce, Corey Bradley, Gautam Borthakur, Abhishek Maiti, Yesid Alvarado, Naveen Pemmaraju, Alessandra Ferrajoli, Mahesh Swaminathan, Maro Ohanian, Hussein A Abbas, Danielle Hammond, Jan Burger, Fadi Haddad, Guillermo Montalban-Bravo, Kelly Chien, Lucia Masarova, Musa Yilmaz, Nitin Jain, Michael Andreeff, Guillermo Garcia-Manero, Steven Kornblau, Farhad Ravandi, Elias Jabbour, Marina Y Konopleva, Hagop M Kantarjian

Faculty, Staff and Student Publications

Intensive chemotherapy remains the standard for newly diagnosed (ND) acute myeloid leukemia (AML); however, relapse risk remains high. Additionally, most patients with relapsed/refractory (RR) AML have poor outcomes. We report the long-term experience of 138 patients, 77 ND and 61 RR, treated with FLAG-IDA in combination with venetoclax. In the ND cohort, the overall response rate (ORR) was 97%, with a composite complete remission (CRc) rate of 95% and undetectable measurable residual disease (MRD) status by flow cytometry in 90%. The 3-year OS and EFS rates were 66 and 64%, respectively. Outcomes were similar across European LeukemiaNet (ELN) 2022 risk …

Longitudinal Tracking Of Alk-Rearranged Nsclc From Plasma Using Circulating Tumor Rna And Circulating Tumor Dna, Simon Heeke, Saumil Gandhi, Hai T Tran, Vincent K Lam, Lauren A Byers, Don L Gibbons, Carl M Gay, Mehmet Altan, Mara B Antonoff, Xiuning Le, Janet Tu, Maliazurina B Saad, Michelle Pek, Jonathan Poh, Kao Chin Ngeow, Anne Tsao, Tina Cascone, Marcelo V Negrao, Jia Wu, George R Blumenschein, John V Heymach, Yasir Y Elamin

Faculty, Staff and Student Publications

Background: Although the administration of tyrosine-kinase inhibitors in ALK-rearranged NSCLC has revolutionized precision medicine, the detection of gene rearrangements from liquid biopsies remains challenging. RNA-based detection has revealed promising sensitivity for rearrangement detection and thus we hypothesize that a liquid biopsy assay analyzing circulating tumor RNA (ctRNA) in addition to circulating tumor DNA (ctDNA) will improve detection. Furthermore, we hypothesize that the detection of gene fusions at baseline will correlate with clinical outcomes.

Methods: We retrospectively analyzed 86 plasma samples from 33 patients enrolled in the BRIGHTSTAR clinical trial assessing local consolidative therapy (LCT) and brigatinib in patients with …

Insulin-Like Growth Factor 2 As A Driving Force For Exponential Expansion And Differentiation Of The Neonatal Thymus, Seung Woo Kang, Bryan R Helm, Yu Wang, Shiyun Xiao, Wen Zhang, Anusha Vasudev, Ken S Lau, Qi Liu, Ellen R Richie, Laura P Hale, Nancy R Manley

Faculty, Staff and Student Publications

Like all organs, the thymus grows in size and function rapidly during development, but this growth comes to a halt after birth. However, the molecular mechanisms behind such a transition in the thymus remain obscure. Using single-cell RNA sequencing (scRNA-seq) of the murine thymic stroma, we identified that major transcriptomic changes occur in the endothelium and mesenchyme across the transition to homeostasis. Differentially expressed gene and intercellular network analyses of temporally resolved scRNA-seq data revealed fibroblast-derived insulin-like growth factor 2 (IGF2) as a candidate driving neonatal thymic expansion. We demonstrated that IGF2 activity promotes a cortical thymic epithelial cell-specific proliferation …

Cost-Effectiveness Of Personalized Policies For Implementing Organ-At-Risk Sparing Adaptive Radiation Therapy In Head And Neck Cancer, Seyedmohammadhossein Hosseinian, Daniel Suarez-Aguirre, Cem Dede, Raul Garcia, Lucas Mccullum, Mehdi Hemmati, Aysenur Karagoz, Abdallah S R Mohamed, Stephen Y Lai, Katherine A Hutcheson, Amy C Moreno, Kristy K Brock, Fatemeh Nosrat, Clifton D Fuller, Andrew J Schaefer

Faculty, Staff and Student Publications

Background and purpose: The principle of adaptive radiation therapy (ART) is to adjust radiation plans in response to anatomical changes during treatment. The purpose of this study was to develop a decision-making model for implementation of personalized ART that balances the costs and clinical benefits of radiation plan adaptations in head and neck cancer (HNC).

Materials and methods: Using retrospective imaging data from 52 HNC patients, a Markov decision process (MDP) model was developed to determine optimal timing for plan adaptations based on the difference in normal tissue complication probability (ΔNTCP) between planned and delivered doses to organs-at-risk. To capture …

Concurrent Bone Marrow Acute Undifferentiated Leukemia And Mediastinal T‐Lymphoblastic Lymphoma With Identical Set::Nup214 Fusion And Phf6 And Ezh2 Mutations, Qing Wei, Fatima Z Jelloul, Sa A Wang, Guilin Tang, Shaoying Li, Pei Lin, Sanam Loghavi, Huan-You Wang, L Jeffrey Medeiros, Jie Xu

Faculty, Staff and Student Publications

Acute undifferentiated leukemia (AUL) is a rare hematologic malignancy lacking lineage‐specific markers. Concurrent, clonally related AUL and T‐lymphoblastic lymphoma (T‐LBL) has not been reported previously. Here we describe a patient who was diagnosed with AUL in the bone marrow and T‐LBL in the mediastinum after a thorough immunophenotyping by flow cytometry and immunohistochemistry. Despite their immunophenotypic differences, the AUL and T‐LBL showed identical genetic alterations: SET::NUP214 fusion, PHF6, and EZH2 mutations. The patient achieved and remained in complete remission after chemotherapy and stem cell transplantation. This case underscores the value of comprehensive immunophenotyping and genetic analysis in rare hematologic …

American College Of Radiology Manual On Mr Safety: 2024 Update And Revisions, Ivan Pedrosa, David A Altman, Jonathan R Dillman, Michael N Hoff, Alexander M Mckinney, Scott B Reeder, Jeffrey M Rogg, R Jason Stafford, James A Webb, Dina L Hernandez, Robert E Watson

Faculty, Staff and Student Publications

Since the introduction of the American College of Radiology (ACR) MRI safety guidelines in 2002, the indications for use of MRI in clinical care and research have continued to expand. Similarly, MRI technologies have evolved, with multiple field strengths now available for human imaging. While several publications have updated the ACR recommendations since the first guidelines, a single source in a structured format was lacking. Accordingly, the ACR Committee on MR Safety recently updated the online ACR Manual on MR Safety that compiles ACR recommendations for safe use of MRI equipment in humans into a single document. This review describes …

Characterization Of A Time-Resolved, Real-Time Scintillation Dosimetry System For Ultra-High Dose-Rate Radiation Therapy Applications, Alexander Baikalov, Daline Tho, Kevin Liu, Stefan Bartzsch, Sam Beddar, Emil Schüler

Faculty, Staff and Student Publications

Purpose: Scintillation dosimetry has promising qualities for ultra-high-dose-rate (UHDR) radiation therapy (RT), but no system has shown compatibility with mean dose rates (DR¯) above 100 Gy/s and doses per pulse (Dp) exceeding 1.5 Gy typical of UHDR (FLASH)-RT. The aim of this study was to characterize a novel scintillation dosimetry system with the potential of accommodating UHDRs.

Methods and materials: We undertook a thorough dosimetric characterization of the system on an UHDR electron beamline. The system's response as a function of dose, DR¯, Dp, and the pulse dose-rate (DRp) was investigated, as was the system's dose sensitivity (signal per unit …

Defining A 'Cells To Society' Research Framework For Appendiceal Tumours, Andreana N Holowatyj, Michael J Overman, Konstantinos I Votanopoulos, Andrew M Lowy, Patrick Wagner, Mary K Washington, Cathy Eng, Wai Chin Foo, Richard M Goldberg, Mojgan Hosseini, Kamran Idrees, Douglas B Johnson, Ardaman Shergill, Erin Ward, Nicholas C Zachos, Deborah Shelton

Faculty, Staff and Student Publications

Tumours of the appendix — a vestigial digestive organ attached to the colon — are rare. Although we estimate that around 3,000 new appendiceal cancer cases are diagnosed annually in the USA, the challenges of accurately diagnosing and identifying this tumour type suggest that this number may underestimate true population incidence. In the current absence of disease-specific screening and diagnostic imaging modalities, or well-established risk factors, the incidental discovery of appendix tumours is often prompted by acute presentations mimicking appendicitis or when the tumour has already spread into the abdominal cavity — wherein the potential misclassification of appendiceal tumours as …

Dysregulation Of Mirna Expression And Excitation In Mef2c Autism Patient Hipsc-Neurons And Cerebral Organoids, Dorit Trudler, Swagata Ghatak, Michael Bula, James Parker, Maria Talantova, Melissa Luevanos, Sergio Labra, Titas Grabauskas, Sarah Moore Noveral, Mayu Teranaka, Emily Schahrer, Nima Dolatabadi, Clare Bakker, Kevin Lopez, Abdullah Sultan, Parth Patel, Agnes Chan, Yongwook Choi, Riki Kawaguchi, Pawel Stankiewicz, Ivan Garcia-Bassets, Piotr Kozbial, Michael G Rosenfeld, Nobuki Nakanishi, Daniel H Geschwind, Shing Fai Chan, Wei Lin, Nicholas J Schork, Rajesh Ambasudhan, Stuart A Lipton

Faculty, Staff and Students Publications

MEF2C is a critical transcription factor in neurodevelopment, whose loss-of-function mutation in humans results in MEF2C haploinsufficiency syndrome (MHS), a severe form of autism spectrum disorder (ASD)/intellectual disability (ID). Despite prior animal studies of MEF2C heterozygosity to mimic MHS, MHS-specific mutations have not been investigated previously, particularly in a human context as hiPSCs afford. Here, for the first time, we use patient hiPSC-derived cerebrocortical neurons and cerebral organoids to characterize MHS deficits. Unexpectedly, we found that decreased neurogenesis was accompanied by activation of a micro-(mi)RNA-mediated gliogenesis pathway. We also demonstrate network-level hyperexcitability in MHS neurons, as evidenced by excessive synaptic …

Revisions To The Safety Assurance Factors For Electronic Health Record Resilience (Safer) Guides To Update National Recommendations For Safe Use Of Electronic Health Records, Dean F Sittig, Trisha Flanagan, Patricia Sengstack, Rosann T Cholankeril, Sara Ehsan, Amanda Heidemann, Daniel R Murphy, Hojjat Salmasian, Jason S Adelman, Hardeep Singh

Faculty, Staff and Student Publications

The Safety Assurance Factors for Electronic Health Record (EHR) Resilience (SAFER) Guides provide recommendations to healthcare organizations for conducting proactive self-assessments of the safety and effectiveness of their EHR implementation and use. Originally released in 2014, they were last updated in 2016. In 2022, the Centers for Medicare and Medicaid Services required their annual attestation by US hospitals.

Objectives: This case study describes how SAFER Guide recommendations were updated to align with current evidence and clinical practice.

Materials and methods: Over nine months, a multidisciplinary team updated SAFER Guides through literature reviews, iterative feedback, and online meetings.

Results: We reduced …

Cytotoxic And Regulatory T Cell Interactions Calculated From Image Mass Cytometry Predict Immunochemotherapy Response In Triple-Negative Breast Cancer, Xiang Wang, Jing Dong, Jian-Rong Li, Yupei Lin, Bikram Sahoo, Yong Li, Yanhong Liu, Robert Taylor Ripley, Jia Wu, Jianjun Zhang, Christopher I Amos, Chao Cheng

Faculty, Staff and Student Publications

No abstract provided.

Differentiation Stage Predicts Radiosensitivity In Mesenchymal-Like Pancreatic Cancer, Tingshi Su, Xinjian Yu, Mojtaba Hoseini-Ghahfarokhi, David B Flint, Scott J Bright, Joana I D S Antunes, David K J Martinus, Mandira Manandhar, Mariam Ben Kacem, Poliana C Marinello, Eurico J G Pereira, Hua-Sheng Chiu, Uwe Titt, David R Grosshans, Jan Schuemann, Henning Willers, Harald Paganetti, Pavel Sumazin, Gabriel O Sawakuchi

Faculty, Staff and Student Publications

Purpose: To derive a genomic classifier to predict radiosensitivity of pancreatic cancer cell lines and patients with pancreatic cancer to allow genomic-guided radiation therapy.

Methods and materials: We collected a comprehensive data set of full clonogenic cell survival curves of 45 pancreatic cancer cell lines irradiated with clinical photon and proton beams. We derived classifiers based on data from human embryonic and fetal pancreas single-cell RNA-sequencing to distinguish between epithelial and mesenchymal cells and to predict pancreas cell-line differentiation stage. Independent testing was done with an embryonic mouse pancreas single-cell RNA-sequencing data set. We then used bulk RNA-seq profiles from …

Endogenous Dna Damage At Sites Of Terminated Transcripts, Jingjing Liu, Jullian O Perren, Cody M Rogers, Sadeieh Nimer, Alice X Wen, Jennifer A Halliday, Devon M Fitzgerald, Qian Mei, Ralf B Nehring, Mary Crum, Stanislav G Kozmin, Jun Xia, Matthew B Cooke, Yin Zhai, David Bates, Lei Li, P J Hastings, Irina Artsimovitch, Christophe Herman, Patrick M Sung, Kyle M Miller, Susan M Rosenberg

Faculty, Staff and Students Publications

DNA damage promotes mutations that fuel cancer, aging, and neurodegenerative diseases1–3, but surprisingly, the causes and types of damage remain largely unknown. There are three identified mechanisms that damage DNA during transcription: RNA polymerase (RNAP) colliding with DNA-replication machinery head-on and co-directionally4–6, and R-loop-induced DNA breakage7–10. Here, we identify DNA-damage reaction intermediates11,12 uncharacterized previously in living cells, and uncover a surprising fourth transcription-related source: endogenous DNA damage at sites of terminated transcripts. We engineered proteins to capture single-stranded (ss)DNA ends with 3'-polarity, in both bacterial …

Destructive And Protective Effects And Therapeutic Targets Of Il-36 Family Cytokines In Dry Eye Disease, Xin Chen, Na Lin, Haixia Liu, Jing Lin, Ning Gao, Zhao Liu, Cintia S De Paiva, Stephen C Pflugfelder, De-Quan Li

Faculty, Staff and Students Publications

Purpose: To explore the destructive and protective effects and therapeutic targets of IL-36 cytokines in dry eye disease using a murine dry eye model.

Methods: A dry eye model was established in C57BL/6 mice exposed to desiccating stress (DS) with untreated mice as controls. A topical challenge model was performed in normal mice with exogenous rmIL-36α, rhIL-38 and 2 % ectoine, or PBS vehicle. IL-36 cytokine expression was assessed by RT-qPCR and immunofluorescent (IF) staining. Corneal epithelial damage was evaluated by corneal smoothness score, Oregon Green Dextran (OGD) fluorescent staining, and tight junction barrier.

Results: All members of the IL-36 …

Oral Decitabine Cedazuridine With And Without Venetoclax In Higher-Risk Myelodysplastic Syndromes Or Chronic Myelomonocytic Leukemia: A Propensity Score-Matched Study, Alex Bataller, Koji Sasaki, Samuel Urrutia, Guillermo Montalban-Bravo, Alexandre Bazinet, Kelly Chien, Danielle Hammond, Ian M Bouligny, Mahesh Swaminathan, Ghayas Issa, Nicholas Short, Naval Daver, Courtney D Dinardo, Tapan Kadia, Elias Jabbour, Farhad Ravandi, Gail J Roboz, Michael Savona, Elizabeth A Griffiths, James Mccloskey, Olatoyosi Odenike, Aram Oganesian, Harold N Keer, Mohammad Azab, Hagop Kantarjian, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

Hypomethylating agents (HMA) are indicated in the treatment of higher-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). The combination of hypomethylating agents with venetoclax (Ven) has demonstrated promising results in these diseases, although randomized clinical trials are needed for validation. In this retrospective study, we compared two matched cohorts of patients with MDS or CMML: one receiving oral decitabine-cedazuridine (DEC-C, n = 73) and one receiving DEC-C and Ven (DEC-C-Ven, n = 51), in three contemporary clinical trials. The aim is to determine the impact of the addition of Ven to HMA in MDS and CMML. Individuals were matched …

Galectin-1 Inhibition As A Strategy For Malignant Peripheral Nerve Sheath Tumor Treatment, Hsiao-Chi Wang, Keila E Torres, Roger Xia, Marcio H Malogolowkin, Ssu-Wei Hsu, Ching-Hsien Chen, Tsung-Chieh Shih

Faculty, Staff and Student Publications

Neurofibromatosis type 1 (NF1) is an inherited disorder that predisposes individuals to malignant peripheral nerve sheath tumors (MPNSTs), a highly aggressive sarcoma with limited treatment options and poor prognosis. This study explores the potential of targeting the interaction between Galectin-1 and Ras as a novel therapeutic strategy for MPNSTs. Through molecular docking, we identified critical residues involved in the Galectin-1 and H-Ras interaction. We developed LLS30, a compound designed to target this Ras-binding pocket on Galectin-1, and tested its efficacy. LLS30 effectively disrupted the Galectin-1/Ras interaction, causing Ras delocalization from the plasma membrane and inhibiting Ras signaling. In vitro experiments …

Oral Decitabine Cedazuridine With And Without Venetoclax In Higher-Risk Myelodysplastic Syndromes Or Chronic Myelomonocytic Leukemia: A Propensity Score-Matched Study, Alex Bataller, Koji Sasaki, Samuel Urrutia, Guillermo Montalban-Bravo, Alexandre Bazinet, Kelly Chien, Danielle Hammond, Ian M Bouligny, Mahesh Swaminathan, Ghayas Issa, Nicholas Short, Naval Daver, Courtney D Dinardo, Tapan Kadia, Elias Jabbour, Farhad Ravandi, Gail J Roboz, Michael Savona, Elizabeth A Griffiths, James Mccloskey, Olatoyosi Odenike, Aram Oganesian, Harold N Keer, Mohammad Azab, Hagop Kantarjian, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

Hypomethylating agents (HMA) are indicated in the treatment of higher-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). The combination of hypomethylating agents with venetoclax (Ven) has demonstrated promising results in these diseases, although randomized clinical trials are needed for validation. In this retrospective study, we compared two matched cohorts of patients with MDS or CMML: one receiving oral decitabine-cedazuridine (DEC-C, n = 73) and one receiving DEC-C and Ven (DEC-C-Ven, n = 51), in three contemporary clinical trials. The aim is to determine the impact of the addition of Ven to HMA in MDS and CMML. Individuals were matched …

Development And Analysis Of The Kinematic-Dynamic Model Of The Rehabilitation Exoskeleton System, Umidjon Abdumutalipovich Takabaev, Zafar Botirovich Juraev

Technical science and innovation

Designing modern rehabilitation exoskeleton systems requires a comprehensive study of human-machine interactions. In this process, creating kinematic and dynamic mathematical models of the system is extremely important. In this paper, we develop mathematical models that describe rehabilitation exoskeleton systems' kinematic and dynamic properties. Based on the Denavit-Hartenberg method we construct kinematic model of the exoskeleton system. The method gave us to determine the coordinate system for each joint. Furthermore, we also study the motion range of joints of the exoskeleton. Modeling the dynamic properties of the system performed with the second-order Lagrange equation. The exoskeleton construction consisting of knee, thigh, …

Outcomes Of Surgically Implanted Impella Microaxial Flow Pumps In Heart Failure-Related Cardiogenic Shock, Jacob Abraham, Mark Anderson, Scott Silvestry, Edward G Soltesz, Masahiro Ono, Kanika Mody, Fardad Esmailian, Arman Kilic, Rupinder Bharmi, Rothy Chhim, Roberta Bogaev-Chapman, Gundars J Katlaps, Ismael Salas De Armas, Mani A Daneshmand, David J Kaczorowski, Duc Thinh Pham, Danny Ramzy, David D'Alessandro

Faculty, Staff and Student Publications

Background: Patients with cardiogenic shock (CS) are increasingly treated with high-profile microaxial flow pumps (Impella 5.5), but little is known about the indications and outcomes of this support strategy in patients with CS due to heart failure (HF-CS).

Objectives: We sought to describe the clinical features and outcomes of patients with HF-CS treated with Impella 5.5.

Methods: We analyzed data from a prospective, multicenter observational study of patients with CS who had been implanted with an Impella 5.5. Adverse events, in-hospital survival rates and 6- and 12-month survival rates were analyzed in the total cohort and between patients treated with …