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Articles 7501 - 7530 of 8886

Full-Text Articles in Biomedical Informatics

Accurate Prediction Of Functional Effect Of Single Amino Acid Variants With Deep Learning, Houssemeddine Derbel, Zhongming Zhao, Qian Liu Jan 2023

Accurate Prediction Of Functional Effect Of Single Amino Acid Variants With Deep Learning, Houssemeddine Derbel, Zhongming Zhao, Qian Liu

Faculty, Staff and Student Publications

The assessment of functional effect of amino acid variants is a critical biological problem in proteomics for clinical medicine and protein engineering. Although natively occurring variants offer insights into deleterious variants, high-throughput deep mutational experiments enable comprehensive investigation of amino acid variants for a given protein. However, these mutational experiments are too expensive to dissect millions of variants on thousands of proteins. Thus, computational approaches have been proposed, but they heavily rely on hand-crafted evolutionary conservation, limiting their accuracy. Recent advancement in transformers provides a promising solution to precisely estimate the functional effects of protein variants on high-throughput experimental data. …


Optimal Ranking And Directional Signature Classification Using The Integral Strategy Of Multi-Objective Optimization-Based Association Rule Mining Of Multi-Omics Data, Saurav Mallik, Soumita Seth, Amalendu Si, Tapas Bhadra, Zhongming Zhao Jan 2023

Optimal Ranking And Directional Signature Classification Using The Integral Strategy Of Multi-Objective Optimization-Based Association Rule Mining Of Multi-Omics Data, Saurav Mallik, Soumita Seth, Amalendu Si, Tapas Bhadra, Zhongming Zhao

Faculty, Staff and Student Publications

No abstract provided.


3pnmf-Mkl: A Non-Negative Matrix Factorization-Based Multiple Kernel Learning Method For Multi-Modal Data Integration And Its Application To Gene Signature Detection\, Saurav Mallik, Anasua Sarkar, Sagnik Nath, Ujjwal Maulik, Supantha Das, Soumen Kumar Pati, Soumadip Ghosh, Zhongming Zhao Jan 2023

3pnmf-Mkl: A Non-Negative Matrix Factorization-Based Multiple Kernel Learning Method For Multi-Modal Data Integration And Its Application To Gene Signature Detection\, Saurav Mallik, Anasua Sarkar, Sagnik Nath, Ujjwal Maulik, Supantha Das, Soumen Kumar Pati, Soumadip Ghosh, Zhongming Zhao

Faculty, Staff and Student Publications

In this current era, biomedical big data handling is a challenging task. Interestingly, the integration of multi-modal data, followed by significant feature mining (gene signature detection), becomes a daunting task. Remembering this, here, we proposed a novel framework, namely, three-factor penalized, non-negative matrix factorization-based multiple kernel learning with soft margin hinge loss (3PNMF-MKL) for multi-modal data integration, followed by gene signature detection. In brief, limma, employing the empirical Bayes statistics, was initially applied to each individual molecular profile, and the statistically significant features were extracted, which was followed by the three-factor penalized non-negative matrix factorization method used for data/matrix fusion …


Predictive Modeling Using Shape Statistics For Interpretable And Robust Quality Assurance Of Automated Contours In Radiation Treatment Planning, Zachary T Wooten, Cenji Yu, Laurence E Court, Christine B Peterson Jan 2023

Predictive Modeling Using Shape Statistics For Interpretable And Robust Quality Assurance Of Automated Contours In Radiation Treatment Planning, Zachary T Wooten, Cenji Yu, Laurence E Court, Christine B Peterson

Faculty, Staff and Student Publications

Deep learning methods for image segmentation and contouring are gaining prominence as an automated approach for delineating anatomical structures in medical images during radiation treatment planning. These contours are used to guide radiotherapy treatment planning, so it is important that contouring errors are flagged before they are used for planning. This creates a need for effective quality assurance methods to enable the clinical use of automated contours in radiotherapy. We propose a novel method for contour quality assurance that requires only shape features, making it independent of the platform used to obtain the images. Our method uses a random forest …


Grid Cells, Border Cells, And Discrete Complex Analysis, Yuri Dabaghian Jan 2023

Grid Cells, Border Cells, And Discrete Complex Analysis, Yuri Dabaghian

Faculty, Staff and Student Publications

We propose a mechanism enabling the appearance of border cells-neurons firing at the boundaries of the navigated enclosures. The approach is based on the recent discovery of discrete complex analysis on a triangular lattice, which allows constructing discrete epitomes of complex-analytic functions and making use of their inherent ability to attain maximal values at the boundaries of generic lattice domains. As it turns out, certain elements of the discrete-complex framework readily appear in the oscillatory models of grid cells. We demonstrate that these models can extend further, producing cells that increase their activity toward the frontiers of the navigated environments. …


Pediatric Diarrhea Patients Living In Urban Areas Have A Higher Incidence Of Clostridioides Difficile Infection, Ayodele T Adesoji, Osaro Mgbere, Charles Darkoh Jan 2023

Pediatric Diarrhea Patients Living In Urban Areas Have A Higher Incidence Of Clostridioides Difficile Infection, Ayodele T Adesoji, Osaro Mgbere, Charles Darkoh

Faculty, Staff and Student Publications

Clostridioides difficile infection (CDI) is a major cause of antibiotic-associated diarrhea and an unappreciated contributor to child mortality in low- and middle-income countries where the diagnosis may be difficult. There is little information about the prevalence of CDI among infants, children, and adolescents in Africa. Using a cross-sectional design, seventy-six samples were collected from pediatric patients presenting with diarrhea, including infants (≤ 2 years old), children (2-12 years), and adolescents (13 ≤17 years) from three hospitals between January and December 2019. Demographic data, medical history, and prior antibiotic use were recorded. Toxigenic culture and PCR were used to detect and …


Population-Based Assessment Of The Burden Of Covid-19 Infection In African Countries: A First-Year Report Card And Public Health Implications, Osaro Mgbere, Ogbonna Collins Nwabuko, Olajumoke A Olateju, Omolola E Adepoju, Winston Liaw, Charles Darkoh, Ekere James Essien Jan 2023

Population-Based Assessment Of The Burden Of Covid-19 Infection In African Countries: A First-Year Report Card And Public Health Implications, Osaro Mgbere, Ogbonna Collins Nwabuko, Olajumoke A Olateju, Omolola E Adepoju, Winston Liaw, Charles Darkoh, Ekere James Essien

Faculty, Staff and Student Publications

BACKGROUND: The COVID-19 pandemic constitutes a global health threat and poses a major burden on the African continent. We assessed the real-world burden of COVID-19 infection in African Union (AU) member states to determine the distributional patterns of epidemiological measures during the first 1 year of the pandemic.

METHODS: This retrospective cross-sectional study utilized COVID-19 data from publicly available data repositories of the African Center for Disease Control and Prevention and

RESULTS: A total of 3.21 million cases were reported during the 1-year period, with 2.6 million recoveries, 536,784 cases remaining active, and 77,486 deaths. Most countries (49.1%,

CONCLUSION: Understanding …


Evolutionary Aspects Of Infections: Inflammation And Sickness Behaviors, Robert Dantzer Jan 2023

Evolutionary Aspects Of Infections: Inflammation And Sickness Behaviors, Robert Dantzer

Faculty, Staff and Student Publications

Sickness behavior was conceptualized initially as the behavioral counterpart of the fever response to infectious pathogens. It helps to raise body temperature to its higher setpoint and to maintain it at this new level and it has the additional benefit of enabling a weakened organism to protect itself from other dangers. The discovery of the behavioral effects of proinflammatory cytokines produced by activated immune cells provided a cellular and molecular basis to this phenomenon. The administration of cytokines or cytokine inducers like lipopolysaccharide to healthy rodents allowed to reveal the similarities and differences between inflammation-induced sickness behavior and the fever …


Inhibition Of Nox2 Or Nlrp3 Inflammasome Prevents Cardiac Remote Ischemic Preconditioning, Sandra Benavides, Rodrigo Palavecino, Jaime A Riquelme, Luis Montecinos, José Pablo Finkelstein, Paulina Donoso, Gina Sánchez Jan 2023

Inhibition Of Nox2 Or Nlrp3 Inflammasome Prevents Cardiac Remote Ischemic Preconditioning, Sandra Benavides, Rodrigo Palavecino, Jaime A Riquelme, Luis Montecinos, José Pablo Finkelstein, Paulina Donoso, Gina Sánchez

Faculty, Staff and Student Publications

Introduction: Short episodes of ischemia-reperfusion (IR) in the heart (classical ischemic preconditioning, IPC) or in a limb (remote ischemic preconditioning, RIPC) before a prolonged ischemic episode, reduce the size of the infarct. It is unknown whether IPC and RIPC share common mechanisms of protection. Animals KO for NOX2, a superoxide-producing enzyme, or KO for NLRP3, a protein component of inflammasome, are not protected by IPC. The aim of this study was to investigate if NOX2 or NLRP3 inflammasome are involved in the protection induced by RIPC. Methods: We preconditioned rats using 4 × 5 min periods of IR in the …


Endothelial Activation Impairs The Function Of Small Extracellular Vesicles, Nicolas Herrera-Zelada, Úrsula Zúñiga-Cuevas, Andrés Ramírez-Reyes, Ignacio Norambuena-Soto, Leslye Venegas-Zamora, Mayarling F Troncoso, Alejandra Hernández, Gina Sánchez, Zully Pedrozo, Sergio Lavandero, Jaime A Riquelme Jan 2023

Endothelial Activation Impairs The Function Of Small Extracellular Vesicles, Nicolas Herrera-Zelada, Úrsula Zúñiga-Cuevas, Andrés Ramírez-Reyes, Ignacio Norambuena-Soto, Leslye Venegas-Zamora, Mayarling F Troncoso, Alejandra Hernández, Gina Sánchez, Zully Pedrozo, Sergio Lavandero, Jaime A Riquelme

Faculty, Staff and Student Publications

Small extracellular vesicles are nanosized vesicles (30-200 nm) that can ferry proteins, nucleic acids, and lipids between cells and therefore, have significant potential as biomarkers, drug delivery tools or therapeutic agents. SEVs of endothelial origin have been shown to -among other functions-reduce in vitro ischemia/reperfusion (I/R) injury in cardiomyocytes, but whether a pro-inflammatory state of the endothelium impairs the functionality of these SEVs remains to be elucidated. To test this, human umbilical vein endothelial cells cells were treated with TNF-α 10 ng/mL and the expression of the pro-inflammatory parameters VCAM-1, ICAM-1 and eNOS were determined by Western blot. SEVs were …


Targeting Mcl-1 Protein To Treat Cancer: Opportunities And Challenges, Shady I Tantawy, Natalia Timofeeva, Aloke Sarkar, Varsha Gandhi Jan 2023

Targeting Mcl-1 Protein To Treat Cancer: Opportunities And Challenges, Shady I Tantawy, Natalia Timofeeva, Aloke Sarkar, Varsha Gandhi

Faculty, Staff and Student Publications

Evading apoptosis has been linked to tumor development and chemoresistance. One mechanism for this evasion is the overexpression of prosurvival B-cell lymphoma-2 (BCL-2) family proteins, which gives cancer cells a survival advantage. Mcl-1, a member of the BCL-2 family, is among the most frequently amplified genes in cancer. Targeting myeloid cell leukemia-1 (MCL-1) protein is a successful strategy to induce apoptosis and overcome tumor resistance to chemotherapy and targeted therapy. Various strategies to inhibit the antiapoptotic activity of MCL-1 protein, including transcription, translation, and the degradation of MCL-1 protein, have been tested. Neutralizing MCL-1's function by targeting its interactions …


Reactome Pathway Analysis From Whole-Blood Transcriptome Reveals Unique Characteristics Of Systemic Sclerosis Patients At The Preclinical Stage, Chiara Bellocchi, Xuan Wang, Marka A Lyons, Maurizio Marchini, Maurizio Lorini, Vincenzo Carbonelli, Nicola Montano, Shervin Assassi, Lorenzo Beretta Jan 2023

Reactome Pathway Analysis From Whole-Blood Transcriptome Reveals Unique Characteristics Of Systemic Sclerosis Patients At The Preclinical Stage, Chiara Bellocchi, Xuan Wang, Marka A Lyons, Maurizio Marchini, Maurizio Lorini, Vincenzo Carbonelli, Nicola Montano, Shervin Assassi, Lorenzo Beretta

Faculty, Staff and Student Publications

OBJECTIVE: This study aims to characterize differential expressed pathways (DEP) in subjects with preclinical systemic sclerosis (PreSSc) characterized uniquely by Raynaud phenomenon, specific autoantibodies, and/or capillaroscopy positive for scleroderma pattern.

METHODS: Whole-blood samples from 33 PreSSc with clinical prospective data (baseline and after 4 years of follow-up) and 16 matched healthy controls (HC) were analyzed for global gene expression transcriptome analysis via RNA sequencing. Functional Analysis of Individual Microarray Expression method annotated Reactome individualized pathways. ANOVA analysis identified DEP whose predictive capability were tested in logistic regression models after extensive internal validation.

RESULTS: At 4 years, 42.4% subjects progressed (evolving …


Chronic Restraint Stress Impairs Voluntary Wheel Running But Has No Effect On Food-Motivated Behavior In Mice, Kiersten Scott, Thien Trong Phan, Nabila Boukelmoune, Cobi J Heijnen, Robert Dantzer Jan 2023

Chronic Restraint Stress Impairs Voluntary Wheel Running But Has No Effect On Food-Motivated Behavior In Mice, Kiersten Scott, Thien Trong Phan, Nabila Boukelmoune, Cobi J Heijnen, Robert Dantzer

Faculty, Staff and Student Publications

Chronic restraint stress is known to cause significant alterations of mitochondrial biology. However, its effects on effort-based behavior and the sensitivity of these effects to treatments that restore mitochondrial function have not been assessed. Based on the hypothesis that the behavioral consequences of this stressor should be more severe for an energy demanding activity than for an energy procuring activity, we compared the effects of chronic restraint stress on the performance of male mice trained to use a running wheel or to nose poke for a food reward in an operant conditioning cage. In accordance with our hypothesis, we observed …


Radiographic Response To Neoadjuvant Therapy In Pleural Mesothelioma Should Serve As A Guide For Patient Selection For Cytoreductive Operations, Nathaniel Deboever, Nicolas Zhou, Daniel J Mcgrail, Katarzyna Tomczak, Jacqueline L Oliva, Hope A Feldman, Edwin Parra, Jianjun Zhang, Percy P Lee, Mara B Antonoff, Wayne L Hofstetter, Reza J Mehran, Ravi Rajaram, David C Rice, Jack A Roth, Stephen S Swisher, Ara A Vaporciyan, Mehmet Altan, Annikka Weissferdt, Anne S Tsao, Cara L Haymaker, Boris Sepesi Jan 2023

Radiographic Response To Neoadjuvant Therapy In Pleural Mesothelioma Should Serve As A Guide For Patient Selection For Cytoreductive Operations, Nathaniel Deboever, Nicolas Zhou, Daniel J Mcgrail, Katarzyna Tomczak, Jacqueline L Oliva, Hope A Feldman, Edwin Parra, Jianjun Zhang, Percy P Lee, Mara B Antonoff, Wayne L Hofstetter, Reza J Mehran, Ravi Rajaram, David C Rice, Jack A Roth, Stephen S Swisher, Ara A Vaporciyan, Mehmet Altan, Annikka Weissferdt, Anne S Tsao, Cara L Haymaker, Boris Sepesi

Faculty, Staff and Student Publications

BACKGROUND: Malignant pleural mesothelioma (MPM) is associated with poor prognosis despite advances in multimodal therapeutic strategies. While patients with resectable disease may benefit from added survival with oncologic resection, patient selection for mesothelioma operations often relies on both objective and subjective evaluation metrics. We sought to evaluate factors associated with improved overall survival (OS) in patients with mesothelioma who underwent macroscopic complete resection (MCR).

METHODS: Patients with MPM who received neoadjuvant therapy and underwent MCR were identified in a prospectively maintained departmental database. Clinicopathologic, blood-based, and radiographic variables were collected and included in a Cox regression analysis (CRA). Response to …


Possible Molecular Mechanisms Underlying The Development Of Atherosclerosis In Cancer Survivors, Priyanka Banerjee, Julia Enterría Rosales, Khanh Chau, Minh T H Nguyen, Sivareddy Kotla, Steven H Lin, Anita Deswal, Robert Dantzer, Elizabeth A Olmsted-Davis, Hung Nguyen, Guangyu Wang, John P Cooke, Jun-Ichi Abe, Nhat-Tu Le Jan 2023

Possible Molecular Mechanisms Underlying The Development Of Atherosclerosis In Cancer Survivors, Priyanka Banerjee, Julia Enterría Rosales, Khanh Chau, Minh T H Nguyen, Sivareddy Kotla, Steven H Lin, Anita Deswal, Robert Dantzer, Elizabeth A Olmsted-Davis, Hung Nguyen, Guangyu Wang, John P Cooke, Jun-Ichi Abe, Nhat-Tu Le

Faculty, Staff and Student Publications

Cancer survivors undergone treatment face an increased risk of developing atherosclerotic cardiovascular disease (CVD), yet the underlying mechanisms remain elusive. Recent studies have revealed that chemotherapy can drive senescent cancer cells to acquire a proliferative phenotype known as senescence-associated stemness (SAS). These SAS cells exhibit enhanced growth and resistance to cancer treatment, thereby contributing to disease progression. Endothelial cell (EC) senescence has been implicated in atherosclerosis and cancer, including among cancer survivors. Treatment modalities for cancer can induce EC senescence, leading to the development of SAS phenotype and subsequent atherosclerosis in cancer survivors. Consequently, targeting senescent ECs displaying the SAS …


Chimeric Rnas Reveal Putative Neoantigen Peptides For Developing Tumor Vaccines For Breast Cancer, Brandon Mistretta, Sakuni Rankothgedera, Micah Castillo, Mitchell Rao, Kimberly Holloway, Anjana Bhardwaj, Maha El Noafal, Constance Albarracin, Randa El-Zein, Hengameh Rezaei, Xiaoping Su, Rehan Akbani, Xiaoshan M Shao, Brian J Czerniecki, Rachel Karchin, Isabelle Bedrosian, Preethi H Gunaratne Jan 2023

Chimeric Rnas Reveal Putative Neoantigen Peptides For Developing Tumor Vaccines For Breast Cancer, Brandon Mistretta, Sakuni Rankothgedera, Micah Castillo, Mitchell Rao, Kimberly Holloway, Anjana Bhardwaj, Maha El Noafal, Constance Albarracin, Randa El-Zein, Hengameh Rezaei, Xiaoping Su, Rehan Akbani, Xiaoshan M Shao, Brian J Czerniecki, Rachel Karchin, Isabelle Bedrosian, Preethi H Gunaratne

Faculty, Staff and Student Publications

INTRODUCTION: We present here a strategy to identify immunogenic neoantigen candidates from unique amino acid sequences at the junctions of fusion proteins which can serve as targets in the development of tumor vaccines for the treatment of breastcancer.

METHOD: We mined the sequence reads of breast tumor tissue that are usually discarded as discordant paired-end reads and discovered cancer specific fusion transcripts using tissue from cancer free controls as reference. Binding affinity predictions of novel peptide sequences crossing the fusion junction were analyzed by the MHC Class I binding predictor, MHCnuggets. CD8+ T cell responses against the 15 peptides were …


Comparing Cigarette-Cue Attentional Bias Between People With Hiv/Aids And People With Opioid Use Disorder Who Smoke, Gopalkumar Rakesh, Joseph L Alcorn, Rebika Khanal, Seth S Himelhoch, Craig R Rush Jan 2023

Comparing Cigarette-Cue Attentional Bias Between People With Hiv/Aids And People With Opioid Use Disorder Who Smoke, Gopalkumar Rakesh, Joseph L Alcorn, Rebika Khanal, Seth S Himelhoch, Craig R Rush

Faculty, Staff and Student Publications

BACKGROUND: Special populations like people living with HIV/AIDS (PLWHA) and people with opioid use disorder (OUD) smoke tobacco cigarettes at rates three to four times greater than the general population. Patients with tobacco use disorder exhibit attentional bias (AB) for cigarette cues. Eye tracking can quantify this bias by measuring fixation time (FT) on cigarette and matched neutral cues, to calculate an AB score. Although previous studies have measured this bias in people who smoke without any other comorbid conditions, no study, to our knowledge, has measured or compared this bias in special populations.

METHODS: We performed exploratory analyses on …


The Importance Of "When" In Calorie Restriction-Induced Lifespan Extension, Kristin Eckel-Mahan Jan 2023

The Importance Of "When" In Calorie Restriction-Induced Lifespan Extension, Kristin Eckel-Mahan

Faculty, Staff and Student Publications

No abstract provided.


Targeted Genomic Sequencing Of Tsc1 And Tsc2 Reveals Causal Variants In Individuals For Whom Previous Genetic Testing For Tuberous Sclerosis Complex Was Normal, Hannah D West, Mark Nellist, Rutger W W Brouwer, Mirjam C G N Van Den Hout-Van Vroonhoven, Luiz Gustavo Dufner De Almeida, Femke Hendriks, Peter Elfferich, Meera Raja, Peter Giles, Rosa M Alfano, Angela Peron, Yves Sznajer, Liesbeth De Waele, Anna Jansen, Marije Koopmans, Anneke Kievit, Laura S Farach, Hope Northrup, Julian R Sampson, Laura E Thomas, Wilfred F J Van Ijcken Jan 2023

Targeted Genomic Sequencing Of Tsc1 And Tsc2 Reveals Causal Variants In Individuals For Whom Previous Genetic Testing For Tuberous Sclerosis Complex Was Normal, Hannah D West, Mark Nellist, Rutger W W Brouwer, Mirjam C G N Van Den Hout-Van Vroonhoven, Luiz Gustavo Dufner De Almeida, Femke Hendriks, Peter Elfferich, Meera Raja, Peter Giles, Rosa M Alfano, Angela Peron, Yves Sznajer, Liesbeth De Waele, Anna Jansen, Marije Koopmans, Anneke Kievit, Laura S Farach, Hope Northrup, Julian R Sampson, Laura E Thomas, Wilfred F J Van Ijcken

Faculty, Staff and Student Publications

Tuberous sclerosis complex (TSC) is caused by inactivating variants in TSC1 and TSC2. Somatic mosaicism, as well as the size and complexity of the TSC1 and TSC2 loci, makes variant identification challenging. Indeed, in some individuals with a clinical diagnosis of TSC, diagnostic testing fails to identify an inactivating variant. To improve TSC1 and TSC2 variant detection, we screened the TSC1 and TSC2 genomic regions using targeted HaloPlex custom capture and next-generation sequencing (NGS) in genomic DNA isolated from peripheral blood of individuals with definite, possible or suspected TSC in whom no disease-associated variant had been identified by previous …


Less Is More? First Impressions From Cosmic-313, Pavlos Msaouel Jan 2023

Less Is More? First Impressions From Cosmic-313, Pavlos Msaouel

Faculty, Staff and Student Publications

The COSMIC-313 phase 3 randomized controlled trial tested the triplet combination of cabozantinib with nivolumab and ipilimumab in comparison with nivolumab plus ipilimumab control as fist-line systemic therapy in metastatic clear cell renal cell carcinoma. The first results presented at the 2022 European Society of Medical Oncology Congress are a milestone for the renal cell carcinoma field because they signal the advent of triplet combinations as potential treatment options for our patients. The present commentary highlights some considerations and potential next steps based on these first impressions.


Phase 1/2 Study Of Epacadostat In Combination With Durvalumab In Patients With Metastatic Solid Tumors, Aung Naing, Alain P Algazi, Gerald S Falchook, Benjamin C Creelan, John Powderly, Seth Rosen, Minal Barve, Niharika B Mettu, Pierre L Triozzi, John Hamm, Gongfu Zhou, Chris Walker, Zhiwan Dong, Manish R Patel Jan 2023

Phase 1/2 Study Of Epacadostat In Combination With Durvalumab In Patients With Metastatic Solid Tumors, Aung Naing, Alain P Algazi, Gerald S Falchook, Benjamin C Creelan, John Powderly, Seth Rosen, Minal Barve, Niharika B Mettu, Pierre L Triozzi, John Hamm, Gongfu Zhou, Chris Walker, Zhiwan Dong, Manish R Patel

Faculty, Staff and Student Publications

Background: Targeting programmed cell death protein 1 (PD-1) and indoleamine 2,3-dioxygenase (IDO1) pathways is an appealing option for cancer treatment.

Methods: The open-label, phase 1/2 ECHO-203 study evaluated the safety, tolerability, and efficacy of the IDO1 inhibitor epacadostat in combination with durvalumab, a human anti-PD-L1 monoclonal antibody in adult patients with advanced solid tumors.

Results: The most common treatment-related adverse events were fatigue (30.7%), nausea (21.0%), decreased appetite (13.1%), pruritus (12.5%), maculopapular rash (10.8%), and diarrhea (10.2%). Objective response rate (ORR) in the overall phase 2 population was 12.0%. Higher ORR was observed in immune checkpoint inhibitor (CPI)-naïve patients (16.1%) …


Radiation Therapy Can Be Safely Incorporated Into Pretransplantation Treatment Regimens For Patients With Multiple Myeloma, Ethan P Damron, Muzaffar H Qazilbash, Penny Q Fang, Susan Y Wu, Bouthaina S Dabaja, Gabriela Rondon, Chitra Hosing, Richard E Champlin, Qaiser Bashir, Elizabeth J Shpall, Mark K Knafl, Hans C Lee, Elisabet E Manasanch, Krina Patel, Sheeba K Thomas, Robert Z Orlowski, Donna M Weber, Chelsea C Pinnix, Jillian R Gunther Jan 2023

Radiation Therapy Can Be Safely Incorporated Into Pretransplantation Treatment Regimens For Patients With Multiple Myeloma, Ethan P Damron, Muzaffar H Qazilbash, Penny Q Fang, Susan Y Wu, Bouthaina S Dabaja, Gabriela Rondon, Chitra Hosing, Richard E Champlin, Qaiser Bashir, Elizabeth J Shpall, Mark K Knafl, Hans C Lee, Elisabet E Manasanch, Krina Patel, Sheeba K Thomas, Robert Z Orlowski, Donna M Weber, Chelsea C Pinnix, Jillian R Gunther

Faculty, Staff and Student Publications

Primary treatment of multiple myeloma (MM) often involves systemic induction therapy (SIT) followed by autologous stem cell transplantation (ASCT). Radiation therapy (RT) is sometimes used for palliation; however, many practitioners avoid RT out of concern that future peripheral blood progenitor cell (PBPC) collection required for ASCT may be compromised. In this study, we retrospectively examined the possible effect of RT on PBPC collection. We reviewed the charts of 732 patients with MM treated with RT at our institution from 1999 to 2017, including patients who received RT prior to PBPC collection for planned ASCT. RT plans (both MM and non-MM …


Editorial: Interplay Between Epigenetic Modifiers And Transcription Factors In Driving Cancer Progression, Yongyong Yang, Annalisa Di Ruscio, Satoshi Inoue, Guocan Wang, Shuai Gao Jan 2023

Editorial: Interplay Between Epigenetic Modifiers And Transcription Factors In Driving Cancer Progression, Yongyong Yang, Annalisa Di Ruscio, Satoshi Inoue, Guocan Wang, Shuai Gao

Faculty, Staff and Student Publications

No abstract provided.


Mechanisms Of Resistance To Egfr-Targeted Therapies In Colorectal Cancer: More Than Just Genetics, Christine Parseghian, Madhulika Eluri, Scott Kopetz, Kanwal Raghav Jan 2023

Mechanisms Of Resistance To Egfr-Targeted Therapies In Colorectal Cancer: More Than Just Genetics, Christine Parseghian, Madhulika Eluri, Scott Kopetz, Kanwal Raghav

Faculty, Staff and Student Publications

The development of acquired resistance to anti-EGFR therapies remains poorly understood, with most research to date exploring, and trying to overcome, various genomic mechanisms of resistance. However, recent work supports a model of resistance whereby transcriptomic mechanisms of resistance predominate in the presence of active cytotoxic chemotherapy combined with anti-EGFR therapy in the first-line setting, with a greater predominance of acquired MAPK mutations after single-agent anti-EGFR therapy in the later-line setting. The proposed model has implications for prospective studies evaluating anti-EGFR rechallenge strategies guided by acquired MAPK mutations and highlights the need to address transcriptional mechanisms of resistance.


Keeping Employees Safe During Health Crises: The Effects Of Media Exposure, Hr Practices, And Age, Shuqi Li, Henry R Young, Majid Ghorbani, Byron Y Lee, Daan Van Knippenberg, Russell E Johnson Jan 2023

Keeping Employees Safe During Health Crises: The Effects Of Media Exposure, Hr Practices, And Age, Shuqi Li, Henry R Young, Majid Ghorbani, Byron Y Lee, Daan Van Knippenberg, Russell E Johnson

Faculty, Staff and Student Publications

Occupational health and safety are critical in promoting the wellness of organizations and employees. The COVID-19 pandemic is one of the most life-threatening viruses encountered in recent history, providing a unique opportunity for research to examine factors that drive employee safety behavior. Drawing from terror management theory, we propose and test a moderated mediation model using data collected from employees working during a peak of the pandemic. We identify two sources of influence - one external (i.e., media exposure), and one internal (i.e., HR practices) to the organization - that shape employees' mortality salience and safety behaviors. We find that …


Self-Administered Meditation Application Intervention For Cancer Patients With Psychosocial Distress: A Pilot Study, Gabriel Lopez, Alejandro Chaoul, Carla L Warneke, Aimee J Christie, Catherine Powers-James, Wenli Liu, Santhosshi Narayanan, Marvin Delgado-Guay, Yisheng Li, Eduardo Bruera, Lorenzo Cohen Jan 2023

Self-Administered Meditation Application Intervention For Cancer Patients With Psychosocial Distress: A Pilot Study, Gabriel Lopez, Alejandro Chaoul, Carla L Warneke, Aimee J Christie, Catherine Powers-James, Wenli Liu, Santhosshi Narayanan, Marvin Delgado-Guay, Yisheng Li, Eduardo Bruera, Lorenzo Cohen

Faculty, Staff and Student Publications

BACKGROUND: We explored the use of a novel smart phone-based application (APP) for delivery and monitoring of meditation to treat mood symptoms experienced by cancer patients.

METHODS: We assessed the feasibility of using a meditation delivery and tracking APP over 2-weeks and its impact on cancer patients' self-reported anxiety and depression. Outpatients reporting depression and/or anxiety were recruited and randomized to the APP or waitlist control group. Assessments included an expectancy scale, exit survey, mood rating before and after each meditation, and the Edmonton Symptom Assessment Scale (ESAS-FS), Hospital Anxiety and Depression Scale (HADS), and Pittsburgh Sleep Quality Index (PSQI) …


Resveratrol Rescues Cutaneous Radiation-Induced Dna Damage Via A Novel Ampk/Sirt7/Hmgb1 Regulatory Axis, Yi Jin, Xingyuan Liu, Xiaoting Liang, Jiabin Liu, Jieyu Liu, Zonglin Han, Qianxin Lu, Ke Wang, Bingyao Meng, Chunting Zhang, Minna Xu, Jian Guan, Li Ma, Liang Zhou Jan 2023

Resveratrol Rescues Cutaneous Radiation-Induced Dna Damage Via A Novel Ampk/Sirt7/Hmgb1 Regulatory Axis, Yi Jin, Xingyuan Liu, Xiaoting Liang, Jiabin Liu, Jieyu Liu, Zonglin Han, Qianxin Lu, Ke Wang, Bingyao Meng, Chunting Zhang, Minna Xu, Jian Guan, Li Ma, Liang Zhou

Faculty, Staff and Student Publications

Cutaneous radiation injury (CRI) interrupts the scheduled process of radiotherapy and even compromises the life quality of patients. However, the current clinical options for alleviating CRI are relatively limited. Resveratrol (RSV) has been shown to be a promising protective agent against CRI; yet the mechanisms of RSV enhancing radioresistance were not fully elucidated and limited its clinical application. In this study, we demonstrate RSV promotes cutaneous radioresistance mainly through SIRT7. During ionizing radiation (IR) treatment, RSV indirectly phosphorylates and activates SIRT7 through AMPK, which is critical for maintaining the genome stability of keratinocytes. Immunoprecipitation and mass spectrometry identified HMGB1 to …


Assessing The Most Vulnerable Subgroup To Type Ii Diabetes Associated With Statin Usage: Evidence From Electronic Health Record Data, Xinzhou Guo, Waverly Wei, Molei Liu, Tianxi Cai, Chong Wu, Jingshen Wang Jan 2023

Assessing The Most Vulnerable Subgroup To Type Ii Diabetes Associated With Statin Usage: Evidence From Electronic Health Record Data, Xinzhou Guo, Waverly Wei, Molei Liu, Tianxi Cai, Chong Wu, Jingshen Wang

Faculty, Staff and Student Publications

There have been increased concerns that the use of statins, one of the most commonly prescribed drugs for treating coronary artery disease, is potentially associated with the increased risk of new-onset Type II diabetes (T2D). Nevertheless, to date, there is no robust evidence supporting as to whether and what kind of populations are indeed vulnerable for developing T2D after taking statins. In this case study, leveraging the biobank and electronic health record data in the Partner Health System, we introduce a new data analysis pipeline and a novel statistical methodology that address existing limitations by (i) designing a rigorous causal …


Self-Assembling Peptides As Immunomodulatory Biomaterials, Andrea Hernandez, Jeffrey D Hartgerink, Simon Young Jan 2023

Self-Assembling Peptides As Immunomodulatory Biomaterials, Andrea Hernandez, Jeffrey D Hartgerink, Simon Young

Faculty, Staff and Student Publications

Self-assembling peptides are a type of biomaterial rapidly emerging in the fields of biomedicine and material sciences due to their promise in biocompatibility and effectiveness at controlled release. These self-assembling peptides can form diverse nanostructures in response to molecular interactions, making them versatile materials. Once assembled, the peptides can mimic biological functions and provide a combinatorial delivery of therapeutics such as cytokines and drugs. These self-assembling peptides are showing success in biomedical settings yet face unique challenges that must be addressed to be widely applied in the clinic. Herein, we describe self-assembling peptides' characteristics and current applications in immunomodulatory therapeutics.


Safety Of Concurrent Radiation Therapy With Brentuximab Vedotin In The Treatment Of Lymphoma, Susan Y Wu, Penny Q Fang, Ethan B Wang, Sairah Ahmed, Madeleine Duvic, Preetesh Jain, Luis E Malpica Castillo, Ranjit Nair, Raphael E Steiner, Paolo Strati, Auris O Huen, Swaminathan P Iyer, Chelsea C Pinnix, Bouthaina S Dabaja, Jillian R Gunther Jan 2023

Safety Of Concurrent Radiation Therapy With Brentuximab Vedotin In The Treatment Of Lymphoma, Susan Y Wu, Penny Q Fang, Ethan B Wang, Sairah Ahmed, Madeleine Duvic, Preetesh Jain, Luis E Malpica Castillo, Ranjit Nair, Raphael E Steiner, Paolo Strati, Auris O Huen, Swaminathan P Iyer, Chelsea C Pinnix, Bouthaina S Dabaja, Jillian R Gunther

Faculty, Staff and Student Publications

PURPOSE: Purpose: Radiation therapy (RT) and the antibody-drug conjugate brentuximab vedotin (BV) are standard-of-care treatment options for patients with certain B and T-cell lymphomas; however, there are limited data exploring the safety of concurrent BV and RT (BVRT).

METHODS AND MATERIALS: We performed a single institutional retrospective review of 44 patients who received BVRT.

RESULTS: Twenty percent of patients (9/44) developed new grade 2 or higher (G2+) hematologic toxicity (HT) after BVRT, which was associated with radiation dose (median dose of 35 Gy in those with new G2+ HT compared with 15 Gy in those without;

CONCLUSIONS: Our analysis demonstrates …