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SSRN 2023年

作者： Jeong, Jaesik Oh, Youngjae Kim, Shinjune Kim, Seongho Department of Statistics Chonnam National University Gwangju61186 Korea Republic of Department of Bigdata Convergence Chonnam National University Gwangju61186 Korea Republic of Statistics Korea Deajeon35208 Korea Republic of Deaprtment of Biomedical Research Institute Gyeongsang National University hospital Jinju52727 Korea Republic of Biostatistics and Bioinformatics Core Karmanos Cancer Institute DetroitMI48201 United States Department of Oncology School of Medicine Wayne State University DetroitMI48201 United States

We present metabolite identification software in the form of R Shiny. Metabolite identification by mass spectral matching in gas chromatography (GC-MS)-based untargeted metabolomics can be done by using the easy-to-use software. Various similarity measures are given and toy example using graphical user interface is presented. © 2023, The Authors. All rights reserved.

关键词： Gas chromatography

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Prognostic factors for clinical outcomes of patients with central nervous system leukemia

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Hematology/ Oncology and Stem Cell Therapy 2021年第3期14卷 240-245页

作者： Bharucha, Jinai Cao, Qing Sachs, Zohar Smith, Angela Williams, Sarah Amin, Khalid Bachanova, Veronika Warlick, Erica Brunstein, Claudio Weisdorf, Daniel Bejanyan, Nelli University of Minnesota Medical School Minneapolis MN United States Biostatistics and Bioinformatics Core Masonic Cancer Center University of Minnesota Minneapolis MN United States Division of Hematology Oncology and Transplantation Department of Medicine University of Minnesota Minneapolis MN United States Division of Blood and Marrow Transplantation Department of Pediatrics University of Minnesota Minneapolis MN United States Department of Laboratory Medicine and Pathology University of Minnesota Minneapolis MN United States Department of Blood and Marrow Transplant and Cellular Immunotherapy Moffitt Cancer Center Tampa FL United States

Prognostic factors associated with clinical outcomes of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) patients with central nervous system (CNS) involvement are unknown. We retrospectively studied the characteristics and outcomes of 66 (18 pediatric and 48 adult) patients with CNS leukemia with ALL (n = 41) or AML (n = 25). The median age of patients at diagnosis of CNS leukemia was 30 (range, 1–69) years. Nearly two-third patients had CNS involvement at the initial diagnosis of leukemia. Complete remission of CNS leukemia was attained in 58 (88%) patients, and probability of overall survival at 36 months after the diagnosis of CNS leukemia was 43% for the entire cohort. We identified that achieving remission of systemic leukemia and having CNS leukemia diagnosed and treated before allogeneic transplantation were the factors associated with CNS leukemia remission. Prognostic factors associated with better overall survival in patients with CNS leukemia included pediatric age, diagnosis of CNS leukemia before receiving allogenic transplantation, achieving clearance of systemic or CNS leukemia, receiving no cranial radiation in conjunction with intrathecal chemotherapy (IT), and receiving IT consolidation after achieving remission of CNS leukemia. Our findings show that patients with CNS leukemia are at considerable risk of mortality. Awareness of modifiable prognostic factors such as avoidance of cranial radiation whenever possible and use of IT consolidation can result in improved outcomes in subset of patients with CNS leukemia. © 2020 King Faisal Specialist Hospital & Research Centre

关键词： ALL AML CNS Leukemia Prognosis

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Low-dose interleukin-2 promotes immune regulation in face transplantation: A pilot study

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American Journal of Transplantation 2023年第4期23卷 549-558页

作者： Murakami, Naoka Borges, Thiago J. Win, Thet Su Abarzua, Phammela Tasigiorgos, Sotirios Kollar, Branislav Barrera, Victor Ho Sui, Shannan Teague, Jessica E. Bueno, Ericka Clark, Rachael A. Lian, Christine G. Murphy, George F. Pomahac, Bohdan Riella, Leonardo V. Transplant Research Center Brigham and Women's Hospital Harvard Medical School Boston MD United States Center for Transplantation Sciences Massachusetts General Hospital Harvard Medical School Boston MD United States Division of Plastic Surgery Department of Surgery Brigham and Women's Hospital Harvard Medical School Boston MD United States Department of Dermatology Brigham and Women's Hospital Harvard Medical School Boston MD United States Department of Pathology Brigham and Women's Hospital Harvard Medical School Boston MD United States Department of Plastic and Hand Surgery University of Freiburg Medical Center Medical Faculty of the University of Freiburg Freiburg Germany Bioinformatics Core Department of Biostatistics Harvard T.H. Chan School of Public Health Boston MD United States Department of Surgery Division of Plastic and Reconstructive Surgery Yale New Haven Hospital Yale School of Medicine New Haven CT United States

Face transplantation is a life-changing procedure for patients with severe composite facial defects. However, it is hampered by high acute rejection rates due to the immunogenicity of skin allograft and toxicity linked to high doses of immunosuppression. To reduce immunosuppression-associated complications, we, for the first time in face transplant recipients, used low-dose interleukin 2 (IL-2) therapy to expand regulatory T cells (Tregs) in vivo and to enhance immune modulation, under close immunological monitoring of peripheral blood and skin allograft. Low-dose IL-2 achieved a sustained expansion (∼4-fold to 5-fold) of circulating Tregs and a reduction (∼3.5-fold) of B cells. Post-IL-2 Tregs exhibited greater suppressive function, characterized by higher expression of TIM-3 and LAG3co-inhibitory molecules. In the skin allograft, Tregs increased after low-dose IL-2 therapy. IL-2 induced a distinct molecular signature in the allograft with reduced cytotoxicity-associated genes (granzyme B and perforin). Two complications were observed during the trial: one rejection event and an episode of autoimmune hemolytic anemia. In summary, this initial experience demonstrated that low-dose IL-2 therapy was not only able to promote immune regulation in face transplant recipients but also highlighted challenges related to its narrow therapeutic window. More specific targeted Treg expansion strategies are needed to translate this approach to the clinic. © 2023 American Society of Transplantation & American Society of Transplant Surgeons

关键词： face transplantation IL-2 immune regulation vascularized composite allograft

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HTRS2023.O6A.3 Identification of major bleeding depends on the definition: an analysis of the Recipient Epidemiology and Donor Evaluation Study (REDS-III) database

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Research and Practice in Thrombosis and Haemostasis 2023年 7卷 100204-100204页

作者： Junior, Alexandre Soares Ferreira Lessa, Morgana Pinheiro Maux Sanborn, Kate Kuchibhatla, Maragatha Onwuemene, Oluwatoyosi A. Faculdade de Medicina de São José do Rio Preto Duke Biostatistics Epidemiology and Research Design Core Duke University School of Medicine Department of Biostatistics and Bioinformatics Duke University School of Medicine Division of Hematology Department of Medicine Duke University School of Medicine

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Aurora Kinase a Inhibition for Gvhd and Relapse Prevention after Allogeneic HCT: Phase I Trial in Combination with Ptcy/Sirolimus

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Transplantation and Cellular Therapy 2024年第2期30卷 S272-S272页

作者： Holtan, Shernan Grace, MD Walton, Kelly El Jurdi, Najla, MD Maakaron, Joseph E., MD Juckett, Mark, MD Bachanova, Veronika, MD, PhD Myers, Thomas J, MD Paradiso, Linda J., DVM, MBA DeFor, Todd E, MS Cao, Qing, MS Betts, Brian C., MD Division of Hematology Oncology and Transplantation University of Minnesota Minneapolis MN University of Minnesota Minneapolis MN Division of Hematology Oncology and Transplantation Department of Medicine University of Minnesota Minneapolis MN Vitrac Therapeutics Natick MA Masonic Cancer Center Biostatistics Core University of Minnesota Minneapolis MN Biostatistics and Bioinformatics Masonic Cancer Center University of Minnesota Minneapolis MN

IntroductionThe rising use of post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis has sparked interest in finding better drug partners to achieve efficient GVHD control while enhancing graft-versus-tumor effects. Sirolimus (SIR) has been used with PTCy. However, it incompletely blocks CD28 co-stimulation in alloreactive T cells. In this context, Aurora kinase A (AURKA) provides an alloreactivity escape route. Combining SIR with AURKA inhibition fully suppresses CD28 signals, thus providing synergistic GVHD prevention in preclinical models. Additionally, AURKA inhibitors possess anti-leukemia properties. Here, we report dose finding results of our first-in-human phase 1 trial using PTCy, SIR, and VIC-1911, a specific oral AURKA inhibitor, for GVHD and relapse prevention post-myeloablative allogeneic hematopoietic cell transplantation (alloHCT). MethodsThe phase I trial (NCT05120570) evaluates the efficacy of AURKA pathway suppression and the safety of the PTCy/SIR/VIC combination. The goal is to determine the lowest biologically effective VIC-1911 dose based on a <54% pH3ser10 expression target in CD4+ T cells at day +21. Patients aged 18-60 years receive myeloablative conditioning of TBI alone at a dose of 1320 cGy. PTCy is given as 50 mg/kg on days +3 and +4, SIR on day +5 with levels targeting 8-12 ng/ml and tapered after day +100, and VIC-1911 is given on days +5 to +45 at doses of 25, 50, or 75 mg BID. Patients receiving PTCy/SIR/mycophenolate mofetil (MMF) in a separate clinical trial serve as controls for studies of CD4+ immunophenotyping. ResultsPrior experiments combining PTCy/SIR with another AURKA inhibitor, alisertib, showed significant protection against GVHD and tumor recurrence in mice (Figure 1A-C). Unlike previous AURKA inhibitors, VIC-1911 shows minimal myelosuppression, justifying this trial. In vitro, VIC-1911 effectively suppresses pH3ser10+ expression in CD4+ T cells (Figure 2A) and kills leukemia cells (Figu

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Reply to Plotkin

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Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2020年第12期71卷 3267-3268页

作者： Ariel M Slifka Byung Park Lina Gao Mark K Slifka Division of Neuroscience Oregon National Primate Research Center Oregon Health & Science University Beaverton Oregon USA. Biostatistics and Bioinformatics Core Oregon National Primate Research Center Biostatistics Shared Resource Knight Cancer Institute Portland Oregon USA.

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Radiation-induced sarcoma of head and neck: Clinical characteristics and molecular signatures

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Head & neck 2023年第3期45卷 638-646页

作者： Yu-Hao Liao Chia-Lang Hsu Chih-Yu Leu Shih-Fan Lai Yen-Lin Huang Min-Shu Hsieh Tseng-Cheng Chen Chun-Nan Chen Cheng-Ping Wang Tsung-Lin Yang Mong-Hsun Tsai Mei-Chun Lin Pei-Jen Lou Department of Otolaryngology National Taiwan University Hospital and College of Medicine National Taiwan University Taipei Taiwan. Department of Otolaryngology National Taiwan University Hospital Hsin-Chu Biomedical Park Branch Hsinchu Taiwan. Department of Medical Research National Taiwan University Hospital Taipei Taiwan. Department of Medical Education National Taiwan University Taipei Taiwan. Division of Radiation Oncology Department of Oncology National Taiwan University Hospital Taipei Taiwan. Department of Pathology National Taiwan University Cancer Center Taipei Taiwan. Department of Pathology National Taiwan University Hospital Taipei Taiwan. Bioinformatics and Biostatistics Core Center of Genomic and Precision Medicine National Taiwan University Taipei Taiwan.

BACKGROUND:Radiation-induced sarcoma of the head and neck (RISHN) is a rare yet devastating potential complication of radiotherapy treatment. We aimed to evaluate the clinicopathological characteristics and molecular signatures of RISHN in patients who underwent radiotherapy for head and neck cancer (HNC) to identify high-risk patients and enable earlier cancer detection. METHODS:This study retrospectively evaluated 24 sarcoma patients who received radiotherapy for HNC between 1994 and 2019. Patients were divided into two groups based on RISHN latency period. Patient demographics, initial tumor staging, risk factors, and survival between groups were analyzed, and whole-exome sequencing (WES) of selected samples was performed. RESULTS:The median age at diagnosis of RISHN was 54 years, and the male-to-female ratio was 2:1. The latency period ranged from 0.8 to 64.4 years (median 6.5 years), with a median survival of 21.5 months. Primary cancer in the oral cavity, treatment with alkylating agents, alcohol consumption, betel nut chewing, and smoking were identified as risk factors for short (<5 years) latency periods. The majority of RISHN cases occurred in the oral cavity (58.3%). WES analysis showed that tumor necrosis factor and cell cycle checkpoint pathways were differentially involved in both patient groups. CONCLUSIONS:Although case numbers were small, our cohort represents the largest case series of RISHN from a single institution to date. Clinicians must be aware of factors affecting RISHN development and latency, and risk factor identification may lead to earlier detection and prevention in the future.

关键词： head and neck cancer latency oral cancer radiation-induced sarcoma whole exome sequencing

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Exploring the genetic correlation of cardiovascular diseases and mood disorders in the UK Biobank

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Epidemiology and psychiatric sciences 2023年 32卷 e31页

作者： Chi-Jen Chen Wan-Yu Liao Amrita Chattopadhyay Tzu-Pin Lu Institute of Epidemiology and Preventive Medicine Department of Public Health College of Public Health National Taiwan University Taipei Taiwan. Bioinformatics and Biostatistics Core Center of Genomics and Precision Medicine Center of Genomics and Precision Medicine National Taiwan University Taipei Taiwan.

AIMS:Cardiovascular diseases (CVDs) are the leading cause of deaths globally. Mortality and incidence of CVDs are significantly higher in people with mood disorders. About 81.1% of CVD patients were reported with comorbidities in 2019, where the second most common comorbidity was due to major depressive disorder (MDD). This study, therefore, aimed to evaluate the genetic correlation between CVDs and mood disorders by using data from the UK Biobank towards understanding the influence of genetic factors on the comorbidity due to CVDs and mood disorders. METHODS:The UK Biobank database provides genetic and health information from half a million adults, aged 40-69 years, recruited between 2006 and 2010. A total of 117,925 participants and 6,128,294 variants were included for analysis after applying exclusion criteria and quality control steps. This study focused on two CVD phenotypes, two mood disorders and 12 cardiometabolic-related traits to conduct association studies. RESULTS:The results indicated a significant positive genetic correlation between CVDs and overall mood disorders and MDD specifically, showing substantial genetic overlap. Genetic correlation between CVDs and bipolar disorder was not significant. Furthermore, significant genetic correlation between mood disorders and cardiometabolic traits was also reported. CONCLUSIONS:The results of this study can be used to understand that CVDs and mood disorders share a great deal of genetic liability in individuals of European ancestry.

关键词： bipolar disorder chronic conditions depression linkage disequilibrium statistics

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Time variation of high-risk groups for liver function deteriorations within fluctuating long-term liver function after hepatic radiotherapy in patients with hepatocellular carcinoma

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European Journal of Medical Research 2024年第1期29卷 104-104页

作者： Tsai, Yu-Lun Yu, Pei-Chieh Nien, Hsin-Hua Lu, Tzu-Pin Institute of Epidemiology and Preventive Medicine College of Public Health National Taiwan University Taipei Taiwan Department of Radiation Oncology Cathay General Hospital Taipei Taiwan School of Medicine China Medical University Taichung Taiwan School of Medicine Fu Jen Catholic University New Taipei City Taiwan Institute of Biomedical Engineering College of Electrical and Computer Engineering National Yang Ming Chiao Tung University Hsinchu Taiwan Bioinformatics and Biostatistics Core Center of Genomic and Precision Medicine National Taiwan University Taipei Taiwan Institute of Health Data Analytics and Statistics College of Public Health National Taiwan University Taipei Taiwan

PURPOSE: The purpose of this study is to find essential risk factors associated with liver function (LF) deteriorations within fluctuating long-term LF and their time-varying effects in patients with hepatocellular carcinoma (HCC) receiving hepatic radiotherapy and to identify high-risk groups for adverse LF deteriorations and their changes over time in facilitating the prevention of hepatic decompensation and the improvement of survival. MATERIALS AND METHODS: A total of 133 HCC patients treated by hepatic radiotherapy were enrolled. A study design was conducted to convert posttreatment long-term LF with fluctuating levels over time to recurrent LF events using defined upgrades in a grading scale. The hazard ratios (HR) of pretreatment biochemical, demographic, clinical, and dosimetric factors in developing posttreatment LF events were estimated using the Cox model. Methodologies of the counting process approach, robust variance estimation, goodness-of-fit testing based on the Schoenfeld residuals, and time-dependent covariates in survival analysis were employed to handle the correlation within subjects and evaluate the time-varying effects during long-term follow-up. RESULTS: Baseline LF score before radiotherapy and gender were significant factors. Initial HR in developing LF events was 1.17 (95% CI 1.11-1.23;P < 0.001) for each increase of baseline LF score and kept almost constant over time (HR, 1.00;95% CI 1.00-1.01;P = 0.065). However, no difference was observed regarding initial hazards for gender (HR, 1.00;95% CI 0.64-1.56;P = 0.994), but the hazard for women got higher monthly over time compared with men (HR, 1.04;95% CI 1.01-1.07;P = 0.006). CONCLUSIONS: High-risk groups for adverse LF deteriorations after hepatic radiotherapy may change over time. Patients with poor baseline LF are vulnerable from the beginning. Women require prevention strategies and careful monitoring for deteriorations at a later stage. © 2024. The Author(s).

关键词： Hepatic radiotherapy Hepatocellular carcinoma High-risk group Long-term liver function Time variation

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SELF-NORMALIZING FOUNDATION MODEL FOR ENHANCED MULTI-OMICS DATA ANALYSIS IN ONCOLOGY

arXiv

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arXiv 2024年

作者： Waqas, Asim Tripathi, Aakash Ahmed, Sabeen Mukund, Ashwin Farooq, Hamza Schabath, Matthew B. Stewart, Paul Naeini, Mia Rasool, Ghulam Johnson, Joseph O. Departments of Cancer Epidemiology and Machine Learning EE Department Moffitt Cancer Center & Research Institute University of South Florida United States Department and Machine Learning Moffitt Cancer Center & Research Institute United States Center for Magnetic Resonance Research University of Minnesota United States Departments of Cancer Epidemiology and Thoracic Oncology Moffitt Cancer Center & Research Institute United States Department of Biostatistics and Bioinformatics Moffitt Cancer Center & Research Institute United States Department of Electrical Engineering University of South Florida United States Department of Machine Learning EE Department Moffitt Cancer Center & Research Institute University of South Florida United States Analytic Microscopy Core Facility Moffitt Cancer Center & Research Institute United States

Multi-omics research has enhanced our understanding of cancer heterogeneity and progression. Investigating molecular data through multi-omics approaches is crucial for unraveling the complex biological mechanisms underlying cancer, thereby enabling more effective diagnosis, treatment, and prevention strategies. However, predicting patient outcomes through the integration of all available multi-omics data is still an under-study research direction. Here, we present SeNMo (Self-normalizing Network for Multi-omics), a foundation model that has been trained on multi-omics data across 33 cancer types. SeNMo is particularly efficient in handling multi-omics data characterized by high-width (many features) and low-length (fewer samples) attributes. We trained SeNMo for the task of overall survival of patients using pan-cancer multi-omics data involving 33 cancer sites from the Genomics Data Commons (GDC). The training multi-omics data includes gene expression, DNA methylation, miRNA expression, DNA mutations, protein expression modalities, and clinical data. SeNMo was validated on two independent cohorts: Moffitt Cancer Center and CPTAC lung squamous cell carcinoma. We evaluated the model’s performance in predicting patient’s overall survival using the concordance index (C-Index). SeNMo performed consistently well in the training regime, reflected by the validation C-Index of 0.76 on GDC’s public data. In the testing regime, SeNMo performed with a C-Index of 0.758 on a held-out test set. The model showed an average accuracy of 99.8% on the task of classifying the primary cancer type on the pan-cancer test cohort. SeNMo demonstrated robust performance on the classification task of predicting the primary cancer type of patients. SeNMo further demonstrated significant performance in predicting tertiary lymph structures from multi-omics data, showing generalizability across cancer types, molecular data types, and clinical endpoints. We believe SeNMo and similar models are pois

关键词： Lung cancer

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