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Articles 27211 - 27240 of 77117

Full-Text Articles in Medical Specialties

Lysosomal Lipid Peroxidation Regulates Tumor Immunity, Monika Bhardwaj, Jennifer J Lee, Amanda M Versace, Sandra L Harper, Aaron R Goldman, Mary Ann S Crissey, Vaibhav Jain, Mahendra Pal Singh, Megane Vernon, Andrew E. Aplin, Seokwoo Lee, Masao Morita, Jeffrey D Winkler, Qin Liu, David W Speicher, Ravi K Amaravadi Apr 2023

Lysosomal Lipid Peroxidation Regulates Tumor Immunity, Monika Bhardwaj, Jennifer J Lee, Amanda M Versace, Sandra L Harper, Aaron R Goldman, Mary Ann S Crissey, Vaibhav Jain, Mahendra Pal Singh, Megane Vernon, Andrew E. Aplin, Seokwoo Lee, Masao Morita, Jeffrey D Winkler, Qin Liu, David W Speicher, Ravi K Amaravadi

Department of Surgery Faculty Papers

Lysosomal inhibition elicited by palmitoyl-protein thioesterase 1 (PPT1) inhibitors such as DC661 can produce cell death, but the mechanism for this is not completely understood. Programmed cell death pathways (autophagy, apoptosis, necroptosis, ferroptosis, and pyroptosis) were not required to achieve the cytotoxic effect of DC661. Inhibition of cathepsins, or iron or calcium chelation, did not rescue DC661-induced cytotoxicity. PPT1 inhibition induced lysosomal lipid peroxidation (LLP), which led to lysosomal membrane permeabilization and cell death that could be reversed by the antioxidant N-acetylcysteine (NAC) but not by other lipid peroxidation antioxidants. The lysosomal cysteine transporter MFSD12 was required for intralysosomal transport …


Microbubble Cavitation Restores Staphylococcus Aureus Antibiotic Susceptibility In Vitro And In A Septic Arthritis Model, Neil Zhao, Dylan Curry, Rachel E Evans, Selin Isguven, Theresa A. Freeman, John R. Eisenbrey, Flemming Forsberg, Jessica M Gilbertie, Sophie Boorman, Rachel Hilliard, Sana S. Dastgheyb, Priscilla Machado, Maria Stanczak, Marc I. Harwood, Antonia F Chen, Javad Parvizi, Irving Shapiro, Noreen J. Hickok, Thomas P Schaer Apr 2023

Microbubble Cavitation Restores Staphylococcus Aureus Antibiotic Susceptibility In Vitro And In A Septic Arthritis Model, Neil Zhao, Dylan Curry, Rachel E Evans, Selin Isguven, Theresa A. Freeman, John R. Eisenbrey, Flemming Forsberg, Jessica M Gilbertie, Sophie Boorman, Rachel Hilliard, Sana S. Dastgheyb, Priscilla Machado, Maria Stanczak, Marc I. Harwood, Antonia F Chen, Javad Parvizi, Irving Shapiro, Noreen J. Hickok, Thomas P Schaer

Department of Orthopaedic Surgery Faculty Papers

Treatment failure in joint infections is associated with fibrinous, antibiotic-resistant, floating and tissue-associated Staphylococcus aureus aggregates formed in synovial fluid (SynF). We explore whether antibiotic activity could be increased against Staphylococcus aureus aggregates using ultrasound-triggered microbubble destruction (UTMD), in vitro and in a porcine model of septic arthritis. In vitro, when bacterially laden SynF is diluted, akin to the dilution achieved clinically with lavage and local injection of antibiotics, amikacin and ultrasound application result in increased bacterial metabolism, aggregate permeabilization, and a 4-5 log decrease in colony forming units, independent of microbubble destruction. Without SynF dilution, amikacin + UTMD does …


Symptom Management Care Pathway Adaptation Process And Specific Adaptation Decisions, Emily Vettese, Farha Sherani, Allison A. King, Lolie Yu, Catherine Aftandilian, Christina Baggott, Vibhuti Agarwal, Ramamoorthy Nagasubramanian, Kara M. Kelly, David R. Freyer, Etan Orgel, Scott M. Bradfield, Wade Kyono, Michael Roth, Lisa M. Klesges, Melissa Beauchemin, Allison Grimes, George Tomlinson, L. Lee Dupuis, Lillian Sung Apr 2023

Symptom Management Care Pathway Adaptation Process And Specific Adaptation Decisions, Emily Vettese, Farha Sherani, Allison A. King, Lolie Yu, Catherine Aftandilian, Christina Baggott, Vibhuti Agarwal, Ramamoorthy Nagasubramanian, Kara M. Kelly, David R. Freyer, Etan Orgel, Scott M. Bradfield, Wade Kyono, Michael Roth, Lisa M. Klesges, Melissa Beauchemin, Allison Grimes, George Tomlinson, L. Lee Dupuis, Lillian Sung

School of Medicine Faculty Publications

BACKGROUND: There is substantial heterogeneity in symptom management provided to pediatric patients with cancer. The primary objective was to describe the adaptation process and specific adaptation decisions related to symptom management care pathways based on clinical practice guidelines. The secondary objective evaluated if institutional factors were associated with adaptation decisions. METHODS: Fourteen previously developed symptom management care pathway templates were reviewed by an institutional adaptation team composed of two clinicians at each of 10 institutions. They worked through each statement for all care pathway templates sequentially. The institutional adaptation team made the decision to adopt, adapt or reject each statement, …


Neurofibroma Of The Internal Carotid Artery Cavernous Sympathetic Plexus: Illustrative Case, Duncan J Trimble, Bryden H Dawes, Hussein A Zeineddine, Katie B Guttenberg, William C Yao, Meenakshi Bhattacharjee, Spiros L Blackburn Apr 2023

Neurofibroma Of The Internal Carotid Artery Cavernous Sympathetic Plexus: Illustrative Case, Duncan J Trimble, Bryden H Dawes, Hussein A Zeineddine, Katie B Guttenberg, William C Yao, Meenakshi Bhattacharjee, Spiros L Blackburn

Faculty, Staff and Student Publications

BACKGROUND: Intracranial carotid sympathetic plexus (CSP) nerve sheath tumors have rarely been reported in the literature. This study describes the first reported case of a CSP neurofibroma and the first case of a CSP nerve sheath tumor treated via an endoscopic endonasal approach followed by adjuvant radiosurgery.

OBSERVATIONS: A 53-year-old man presented with 3 days of headaches and diplopia and was found to have a complete left abducens nerve palsy. Computed tomography (CT) revealed a smoothly dilated left carotid canal, CT angiography revealed a superiorly displaced left internal carotid artery (ICA), and magnetic resonance imaging revealed a T2-hyperintense and avidly …


Stranger Things: New Roles And Opportunities For Androgen Receptor In Oncology Beyond Prostate Cancer, Javier Leo, Eleonora Dondossola, Kaitlin J Basham, Nathaniel R Wilson, Omar Alhalabi, Jianjun Gao, Katherine C Kurnit, Michael G White, Jennifer L Mcquade, Shannon N Westin, Elizabeth A Wellberg, Daniel E Frigo Apr 2023

Stranger Things: New Roles And Opportunities For Androgen Receptor In Oncology Beyond Prostate Cancer, Javier Leo, Eleonora Dondossola, Kaitlin J Basham, Nathaniel R Wilson, Omar Alhalabi, Jianjun Gao, Katherine C Kurnit, Michael G White, Jennifer L Mcquade, Shannon N Westin, Elizabeth A Wellberg, Daniel E Frigo

Faculty, Staff and Student Publications

The androgen receptor (AR) is one of the oldest therapeutic targets in oncology and continues to dominate the treatment landscape for advanced prostate cancer, where nearly all treatment regimens include some form of AR modulation. In this regard, AR remains the central driver of prostate cancer cell biology. Emerging preclinical and clinical data implicate key roles for AR in additional cancer types, thereby expanding the importance of this drug target beyond prostate cancer. In this mini-review, new roles for AR in other cancer types are discussed as well as their potential for treatment with AR-targeted agents. Our understanding of these …


Ether Phospholipids Are Required For Mitochondrial Reactive Oxygen Species Homeostasis, Ziheng Chen, I-Lin Ho, Melinda Soeung, Er-Yen Yen, Jintan Liu, Liang Yan, Johnathon L Rose, Sanjana Srinivasan, Shan Jiang, Q Edward Chang, Ningping Feng, Jason P Gay, Qi Wang, Jing Wang, Philip L Lorenzi, Lucas J Veillon, Bo Wei, John N Weinstein, Angela K Deem, Sisi Gao, Giannicola Genovese, Andrea Viale, Wantong Yao, Costas A Lyssiotis, Joseph R Marszalek, Giulio F Draetta, Haoqiang Ying Apr 2023

Ether Phospholipids Are Required For Mitochondrial Reactive Oxygen Species Homeostasis, Ziheng Chen, I-Lin Ho, Melinda Soeung, Er-Yen Yen, Jintan Liu, Liang Yan, Johnathon L Rose, Sanjana Srinivasan, Shan Jiang, Q Edward Chang, Ningping Feng, Jason P Gay, Qi Wang, Jing Wang, Philip L Lorenzi, Lucas J Veillon, Bo Wei, John N Weinstein, Angela K Deem, Sisi Gao, Giannicola Genovese, Andrea Viale, Wantong Yao, Costas A Lyssiotis, Joseph R Marszalek, Giulio F Draetta, Haoqiang Ying

Faculty, Staff and Student Publications

Mitochondria are hubs where bioenergetics, redox homeostasis, and anabolic metabolism pathways integrate through a tightly coordinated flux of metabolites. The contributions of mitochondrial metabolism to tumor growth and therapy resistance are evident, but drugs targeting mitochondrial metabolism have repeatedly failed in the clinic. Our study in pancreatic ductal adenocarcinoma (PDAC) finds that cellular and mitochondrial lipid composition influence cancer cell sensitivity to pharmacological inhibition of electron transport chain complex I. Profiling of patient-derived PDAC models revealed that monounsaturated fatty acids (MUFAs) and MUFA-linked ether phospholipids play a critical role in maintaining ROS homeostasis. We show that ether phospholipids support mitochondrial …


Cancer Cell-Extrinsic Roles For The Androgen Receptor In Prostate Cancer, Andrew W Hahn, Bilal A Siddiqui, Javier Leo, Eleonora Dondossola, Kaitlin J Basham, Cindy K Miranti, Daniel E Frigo Apr 2023

Cancer Cell-Extrinsic Roles For The Androgen Receptor In Prostate Cancer, Andrew W Hahn, Bilal A Siddiqui, Javier Leo, Eleonora Dondossola, Kaitlin J Basham, Cindy K Miranti, Daniel E Frigo

Faculty, Staff and Student Publications

Given the central role of the androgen receptor (AR) in prostate cancer cell biology, AR-targeted therapies have been the backbone of prostate cancer treatment for over 50 years. New data indicate that AR is expressed in additional cell types within the tumor microenvironment. Moreover, targeting AR for the treatment of prostate cancer has established side effects such as bone complications and an increased risk of developing cardiometabolic disease, indicating broader roles for AR. With the advent of novel technologies, such as single-cell approaches and advances in preclinical modeling, AR has been identified to have clinically significant functions in other cell …


Distinct Astrocytic Modulatory Roles In Sensory Transmission During Sleep, Wakefulness, And Arousal States In Freely Moving Mice, Fushun Wang, Wei Wang, Simeng Gu, Dan Qi, Nathan A Smith, Weiguo Peng, Wei Dong, Jiajin Yuan, Binbin Zhao, Ying Mao, Peng Cao, Qing Richard Lu, Lee A Shapiro, S Stephen Yi, Erxi Wu, Jason H Huang Apr 2023

Distinct Astrocytic Modulatory Roles In Sensory Transmission During Sleep, Wakefulness, And Arousal States In Freely Moving Mice, Fushun Wang, Wei Wang, Simeng Gu, Dan Qi, Nathan A Smith, Weiguo Peng, Wei Dong, Jiajin Yuan, Binbin Zhao, Ying Mao, Peng Cao, Qing Richard Lu, Lee A Shapiro, S Stephen Yi, Erxi Wu, Jason H Huang

Faculty, Staff and Student Publications

Despite extensive research on astrocytic Ca2+ in synaptic transmission, its contribution to the modulation of sensory transmission during different brain states remains largely unknown. Here, by using two-photon microscopy and whole-cell recordings, we show two distinct astrocytic Ca2+ signals in the murine barrel cortex: a small, long-lasting Ca2+ increase during sleep and a large, widespread but short-lasting Ca2+ spike when aroused. The large Ca2+ wave in aroused mice was inositol trisphosphate (IP3)-dependent, evoked by the locus coeruleus-norepinephrine system, and enhanced sensory input, contributing to reliable sensory transmission. However, the small Ca2+ transient was IP3-independent and contributed to decreased extracellular K+, …


The Melanocortin Action Is Biased Toward Protection From Weight Loss In Mice, Hongli Li, Yuanzhong Xu, Yanyan Jiang, Zhiying Jiang, Joshua Otiz-Guzman, Jessie C Morrill, Jing Cai, Zhengmei Mao, Yong Xu, Benjamin R Arenkiel, Cheng Huang, Qingchun Tong Apr 2023

The Melanocortin Action Is Biased Toward Protection From Weight Loss In Mice, Hongli Li, Yuanzhong Xu, Yanyan Jiang, Zhiying Jiang, Joshua Otiz-Guzman, Jessie C Morrill, Jing Cai, Zhengmei Mao, Yong Xu, Benjamin R Arenkiel, Cheng Huang, Qingchun Tong

Faculty, Staff and Student Publications

The melanocortin action is well perceived for its ability to regulate body weight bidirectionally with its gain of function reducing body weight and loss of function promoting obesity. However, this notion cannot explain the difficulty in identifying effective therapeutics toward treating general obesity via activation of the melanocortin action. Here, we provide evidence that altered melanocortin action is only able to cause one-directional obesity development. We demonstrate that chronic inhibition of arcuate neurons expressing proopiomelanocortin (POMC) or paraventricular hypothalamic neurons expressing melanocortin receptor 4 (MC4R) causes massive obesity. However, chronic activation of these neuronal populations failed to reduce body weight. …


Hepatocyte Srebp Signaling Mediates Clock Communication Within The Liver, Dongyin Guan, Hosung Bae, Dishu Zhou, Ying Chen, Chunjie Jiang, Cam Mong La, Yang Xiao, Kun Zhu, Wenxiang Hu, Trang Minh Trinh, Panpan Liu, Ying Xiong, Bishuang Cai, Cholsoon Jang, Mitchell A Lazar Apr 2023

Hepatocyte Srebp Signaling Mediates Clock Communication Within The Liver, Dongyin Guan, Hosung Bae, Dishu Zhou, Ying Chen, Chunjie Jiang, Cam Mong La, Yang Xiao, Kun Zhu, Wenxiang Hu, Trang Minh Trinh, Panpan Liu, Ying Xiong, Bishuang Cai, Cholsoon Jang, Mitchell A Lazar

Faculty, Staff and Students Publications

Rhythmic intraorgan communication coordinates environmental signals and the cell-intrinsic clock to maintain organ homeostasis. Hepatocyte-specific KO of core components of the molecular clock Rev-erbα and -β (Reverb-hDKO) alters cholesterol and lipid metabolism in hepatocytes as well as rhythmic gene expression in nonparenchymal cells (NPCs) of the liver. Here, we report that in fatty liver caused by diet-induced obesity (DIO), hepatocyte SREBP cleavage-activating protein (SCAP) was required for Reverb-hDKO-induced diurnal rhythmic remodeling and epigenomic reprogramming in liver macrophages (LMs). Integrative analyses of isolated hepatocytes and LMs revealed that SCAP-dependent lipidomic changes in REV-ERB-depleted hepatocytes led to the enhancement of LM metabolic …


Safety And Immunogenicity Of Multimeric-001 (M-001) Followed By Seasonal Quadrivalent Inactivated Influenza Vaccine In Young Adults – A Randomized Clinical Trial, Robert L Atmar, David I Bernstein, Patricia Winokur, Sharon E Frey, Laura S Angelo, Christopher Bryant, Tammy Ben-Yedidia, Paul C Roberts, Hana M El Sahly, Wendy A Keitel Apr 2023

Safety And Immunogenicity Of Multimeric-001 (M-001) Followed By Seasonal Quadrivalent Inactivated Influenza Vaccine In Young Adults – A Randomized Clinical Trial, Robert L Atmar, David I Bernstein, Patricia Winokur, Sharon E Frey, Laura S Angelo, Christopher Bryant, Tammy Ben-Yedidia, Paul C Roberts, Hana M El Sahly, Wendy A Keitel

Faculty, Staff and Students Publications

BACKGROUND: The continuing evolution of influenza viruses poses a challenge to vaccine prevention, highlighting the need for a universal influenza vaccine. We evaluated the safety and immunogenicity of one such candidate, Multimeric-001 (M-001), when used as a priming vaccine prior to administration of quadrivalent inactivated influenza vaccine (IIV4).

METHODS: Healthy adults 18 to 49 years of age were enrolled in a phase 2 randomized, double-blind placebo-controlled trial. Participants received two doses of either 1.0-mg M-001 or saline placebo (60 per study arm) on Days 1 and 22 followed by a single dose of IIV4 on about Day 172. Safety, reactogenicity, …


Deep-Learning-Based Hepatic Ploidy Quantification Using H&E Histopathology Images, Zhuoyu Wen, Yu-Hsuan Lin, Shidan Wang, Naoto Fujiwara, Ruichen Rong, Kevin W Jin, Donghan M Yang, Bo Yao, Shengjie Yang, Tao Wang, Yang Xie, Yujin Hoshida, Hao Zhu, Guanghua Xiao Apr 2023

Deep-Learning-Based Hepatic Ploidy Quantification Using H&E Histopathology Images, Zhuoyu Wen, Yu-Hsuan Lin, Shidan Wang, Naoto Fujiwara, Ruichen Rong, Kevin W Jin, Donghan M Yang, Bo Yao, Shengjie Yang, Tao Wang, Yang Xie, Yujin Hoshida, Hao Zhu, Guanghua Xiao

Faculty, Staff and Student Publications

Polyploidy, the duplication of the entire genome within a single cell, is a significant characteristic of cells in many tissues, including the liver. The quantification of hepatic ploidy typically relies on flow cytometry and immunofluorescence (IF) imaging, which are not widely available in clinical settings due to high financial and time costs. To improve accessibility for clinical samples, we developed a computational algorithm to quantify hepatic ploidy using hematoxylin-eosin (H&E) histopathology images, which are commonly obtained during routine clinical practice. Our algorithm uses a deep learning model to first segment and classify different types of cell nuclei in H&E images. …


Initiating And Imaging Cavitation From Infused Echo Contrast Agents Through The Ekosonic Catheter, Sonya R Kennedy, Maxime Lafond, Kevin J Haworth, Daniel Suarez Escudero, Dan Ionascu, Brion Frierson, Shaoling Huang, Melvin E Klegerman, Tao Peng, David D Mcpherson, Curtis Genstler, Christy K Holland Apr 2023

Initiating And Imaging Cavitation From Infused Echo Contrast Agents Through The Ekosonic Catheter, Sonya R Kennedy, Maxime Lafond, Kevin J Haworth, Daniel Suarez Escudero, Dan Ionascu, Brion Frierson, Shaoling Huang, Melvin E Klegerman, Tao Peng, David D Mcpherson, Curtis Genstler, Christy K Holland

Faculty, Staff and Student Publications

Ultrasound-enhanced delivery of therapeutic-loaded echogenic liposomes is under development for vascular applications using the EkoSonic Endovascular System. In this study, fibrin-targeted echogenic liposomes loaded with an anti-inflammatory agent were characterized before and after infusion through an EkoSonic catheter. Cavitation activity was nucleated by Definity or fibrin-targeted, drug-loaded echogenic liposomes infused and insonified with EkoSonic catheters. Passive cavitation imaging was used to quantify and map bubble activity in a flow phantom mimicking porcine arterial flow. Cavitation was sustained during 3-min infusions of Definity or echogenic liposomes along the distal 6 cm treatment zone of the catheter. Though the EkoSonic catheter was …


Empowering Children And Families With Food Allergies: An Innovative Role For Occupational Therapy, Salma H. Bachelani, Meredith P. Gronski, Kelly A. Carlson Apr 2023

Empowering Children And Families With Food Allergies: An Innovative Role For Occupational Therapy, Salma H. Bachelani, Meredith P. Gronski, Kelly A. Carlson

The Open Journal of Occupational Therapy

Food allergies (FAs) have far-reaching implications regarding occupational participation. Children with food allergies and their families experience impacts on their daily life activities. The current standard of care for FAs fails to adequately address the wide-ranging barriers to participation in home, school, and community environments. This study used a mixed-method design to examine the impacts of FA on the needs of children and families affected by FA. Eighteen parents of children with FAs and six health care providers of children with FAs were interviewed; the parents also completed two questionnaires to identify the level of impact of FA on areas …


Flying Under The Radar: A Survey Of Collegiate Pilots’ Mental Health To Identify Aeromedical Nondisclosure And Healthcare-Seeking Behaviors, Emily Faulconer, Lauren Pitts Apr 2023

Flying Under The Radar: A Survey Of Collegiate Pilots’ Mental Health To Identify Aeromedical Nondisclosure And Healthcare-Seeking Behaviors, Emily Faulconer, Lauren Pitts

Publications

The disclosure of a new or existing mental health condition in a pilot complicates their medical certification status. It has been proposed that the threat of losing medical certification often discourages pilots from seeking treatment for mental health issues or disclosing such information to aeromedical professionals, contributing to a barrier to seeking healthcare that affects pilots of all certification levels. The current study focused on the nondisclosure and healthcare-seeking behaviors of the collegiate pilot population(N = 2,452)at a large, accredited, private institution that offers flight training in accordance with Pilot Schools (2022). Data collected from our anonymous online survey over …


Neurocomputational Mechanisms Of Food And Physical Activity Decision-Making In Male Adolescents., Seung-Lark Lim, Amanda S. Bruce, Robin P. Shook Apr 2023

Neurocomputational Mechanisms Of Food And Physical Activity Decision-Making In Male Adolescents., Seung-Lark Lim, Amanda S. Bruce, Robin P. Shook

Manuscripts, Articles, Book Chapters and Other Papers

We examined the neurocomputational mechanisms in which male adolescents make food and physical activity decisions and how those processes are influenced by body weight and physical activity levels. After physical activity and dietary assessments, thirty-eight males ages 14-18 completed the behavioral rating and fMRI decision tasks for food and physical activity items. The food and physical activity self-control decisions were significantly correlated with each other. In both, taste- or enjoyment-oriented processes were negatively associated with successful self-control decisions, while health-oriented processes were positively associated. The correlation between taste/enjoyment and healthy attribute ratings predicted actual laboratory food intake and physical activities …


The Role Of Klotho And Fgf23 In Cardiovascular Outcomes Of Diabetic Patients With Chronic Limb Threatening Ischemia: A Prospective Study, Federico Biscetti, Maria Margherita Rando, Andrea Leonardo Cecchini, Maria Anna Nicolazzi, Enrica Rossini, Flavia Angelini, Roberto Iezzi, Luis H. Eraso, Paul J. Dimuzio, Dario Pitocco, Antonio Gasbarrini, Massimo Massetti, Andrea Flex Apr 2023

The Role Of Klotho And Fgf23 In Cardiovascular Outcomes Of Diabetic Patients With Chronic Limb Threatening Ischemia: A Prospective Study, Federico Biscetti, Maria Margherita Rando, Andrea Leonardo Cecchini, Maria Anna Nicolazzi, Enrica Rossini, Flavia Angelini, Roberto Iezzi, Luis H. Eraso, Paul J. Dimuzio, Dario Pitocco, Antonio Gasbarrini, Massimo Massetti, Andrea Flex

Department of Surgery Faculty Papers

Cardiovascular complications after lower extremity revascularization (LER) are common in diabetic patients with peripheral arterial disease (PAD) and chronic limb threatening ischemia (CLTI). The Klotho-fibroblast growth factor 23 (FGF23) axis is associated with endothelial injury and cardiovascular risk. We aimed to analyze the relationship between Klotho and FGF23 serum levels and the incidence of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) after LER in diabetic patients with PAD and CLTI. Baseline levels of Klotho and FGF23, and their association with subsequent incidence of MACE and MALE were analyzed in a prospective, non-randomized study in a population …


Anthracycline-Containing And Taxane-Containing Chemotherapy For Early-Stage Operable Breast Cancer: A Patient-Level Meta-Analysis Of 100 000 Women From 86 Randomised Trials, Early Breast Cancer Trialists’ Collaborative Group (Ebctcg) Apr 2023

Anthracycline-Containing And Taxane-Containing Chemotherapy For Early-Stage Operable Breast Cancer: A Patient-Level Meta-Analysis Of 100 000 Women From 86 Randomised Trials, Early Breast Cancer Trialists’ Collaborative Group (Ebctcg)

Faculty, Staff and Student Publications

BACKGROUND: Anthracycline-taxane chemotherapy for early-stage breast cancer substantially improves survival compared with no chemotherapy. However, concerns about short-term and long-term side-effects of anthracyclines have led to increased use of taxane chemotherapy without anthracycline, which could compromise efficacy. We aimed to better characterise the benefits and risks of including anthracycline, and the comparative benefits of different anthracycline-taxane regimens.

METHODS: We did an individual patient-level meta-analysis of randomised trials comparing taxane regimens with versus without anthracycline, and updated our previous meta-analysis of anthracycline regimens with versus without taxane, as well as analysing 44 trials in six related comparisons. We searched databases, including …


The Potential Regulation Of A-To-I Rna Editing On Genes In Parkinson's Disease, Sijia Wu, Qiuping Xue, Xinyu Qin, Xiaoming Wu, Pora Kim, Jacqueline Chyr, Xiaobo Zhou, Liyu Huang Apr 2023

The Potential Regulation Of A-To-I Rna Editing On Genes In Parkinson's Disease, Sijia Wu, Qiuping Xue, Xinyu Qin, Xiaoming Wu, Pora Kim, Jacqueline Chyr, Xiaobo Zhou, Liyu Huang

Faculty, Staff and Student Publications

Parkinson's disease (PD) is characterized by dopaminergic neurodegeneration and an abnormal accumulation of α-synuclein aggregates. A number of genetic factors have been shown to increase the risk of PD. Exploring the underlying molecular mechanisms that mediate PD's transcriptomic diversity can help us understand neurodegenerative pathogenesis. In this study, we identified 9897 A-to-I RNA editing events associated with 6286 genes across 372 PD patients. Of them, 72 RNA editing events altered miRNA binding sites and this may directly affect miRNA regulations of their host genes. However, RNA editing effects on the miRNA regulation of genes are more complex. They can (1) …


Flying Under The Radar: A Survey Of Collegiate Pilots’ Mental Health To Identify Aeromedical Nondisclosure And Healthcare-Seeking Behaviors, Lauren Pitts, Emily Faulconer Apr 2023

Flying Under The Radar: A Survey Of Collegiate Pilots’ Mental Health To Identify Aeromedical Nondisclosure And Healthcare-Seeking Behaviors, Lauren Pitts, Emily Faulconer

Publications

The disclosure of a new or existing mental health condition in a pilot complicates their medical certification status. It has been proposed that the threat of losing medical certification often discourages pilots from seeking treatment for mental health issues or disclosing such information to aeromedical professionals, contributing to a barrier to seeking healthcare that affects pilots of all certification levels. The current study focused on the nondisclosure and healthcare-seeking behaviors of the collegiate pilot population(N = 2,452)at a large, accredited, private institution that offers flight training in accordance with Pilot Schools (2022). Data collected from our anonymous online survey over …


Brain Deficit Patterns Of Metabolic Illnesses Overlap With Those For Major Depressive Disorder: A New Metric Of Brain Metabolic Disease, Kathryn S Hatch, Si Gao, Yizhou Ma, Alessandro Russo, Neda Jahanshad, Paul M Thompson, Bhim M Adhikari, Heather Bruce, Andrew Van Der Vaart, Aristeidis Sotiras, Mark D Kvarta, Thomas E Nichols, Lianne Schmaal, L Elliot Hong, Peter Kochunov Apr 2023

Brain Deficit Patterns Of Metabolic Illnesses Overlap With Those For Major Depressive Disorder: A New Metric Of Brain Metabolic Disease, Kathryn S Hatch, Si Gao, Yizhou Ma, Alessandro Russo, Neda Jahanshad, Paul M Thompson, Bhim M Adhikari, Heather Bruce, Andrew Van Der Vaart, Aristeidis Sotiras, Mark D Kvarta, Thomas E Nichols, Lianne Schmaal, L Elliot Hong, Peter Kochunov

Faculty, Staff and Student Publications

Metabolic illnesses (MET) are detrimental to brain integrity and are common comorbidities in patients with mental illnesses, including major depressive disorder (MDD). We quantified effects of MET on standard regional brain morphometric measures from 3D brain MRI as well as diffusion MRI in a large sample of UK BioBank participants. The pattern of regional effect sizes of MET in non-psychiatric UKBB subjects was significantly correlated with the spatial profile of regional effects reported by the largest meta-analyses in MDD but not in bipolar disorder, schizophrenia or Alzheimer's disease. We used a regional vulnerability index (RVI) for MET (RVI-MET) to measure …


Molecular Disparity Of Hla-Dpb1 Is Associated With The Development Of Subsequent Solid Cancer After Allogeneic Hematopoietic Stem Cell Transplantation, Jun Zou, Piyanuch Kongtim, Betül Oran, Samer A Srour, Uri Greenbaum, Yudith Carmazzi, Gabriela Rondon, Stefan O Ciurea, Qing Ma, Elizabeth J Shpall, Richard E Champlin, Kai Cao Apr 2023

Molecular Disparity Of Hla-Dpb1 Is Associated With The Development Of Subsequent Solid Cancer After Allogeneic Hematopoietic Stem Cell Transplantation, Jun Zou, Piyanuch Kongtim, Betül Oran, Samer A Srour, Uri Greenbaum, Yudith Carmazzi, Gabriela Rondon, Stefan O Ciurea, Qing Ma, Elizabeth J Shpall, Richard E Champlin, Kai Cao

Faculty, Staff and Student Publications

Background: An increased incidence of subsequent solid cancers (SSCs) has been reported in long-term survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT), and SSC is associated with inferior mortality and morbidity. Previous studies showed that the incidence of SSC is significantly higher in those who underwent allo-HSCT from HLA-mismatched donors, suggesting that persistent alloimmunity may predispose patients to SSCs. It was recently reported that, in a cohort of patients who received allo-HSCT from an unrelated donor matched at HLA-A, -B, -C, -DRB1/3/4/5, and -DQB1 loci, HLA-DPB1 alloimmunity determined by high mismatched eplets (MEs) and Predicted Indirectly Recognizable HLA Epitopes (PIRCHE) …


Nuclear Export Signal Mutation Of Epidermal Growth Factor Receptor Enhances Malignant Phenotypes Of Cancer Cells, Lei Nie, Ying-Nai Wang, Jung-Mao Hsu, Junwei Hou, Yu-Yi Chu, Li-Chuan Chan, Longfei Huo, Yongkun Wei, Rong Deng, Jun Tang, Yi-Hsin Hsu, How-Wen Ko, Seung-Oe Lim, Kebin Huang, Mei-Kuang Chen, Tai-Jan Chiu, Chien-Chia Cheng, Yueh-Fu Fang, Chia-Wei Li, Aarthi Goverdhan, Hsing-Ju Wu, Cheng-Chung Lee, Wen-Ling Wang, Jennifer Hsu, Paul Chiao, Shao-Chun Wang, Mien-Chie Hung Apr 2023

Nuclear Export Signal Mutation Of Epidermal Growth Factor Receptor Enhances Malignant Phenotypes Of Cancer Cells, Lei Nie, Ying-Nai Wang, Jung-Mao Hsu, Junwei Hou, Yu-Yi Chu, Li-Chuan Chan, Longfei Huo, Yongkun Wei, Rong Deng, Jun Tang, Yi-Hsin Hsu, How-Wen Ko, Seung-Oe Lim, Kebin Huang, Mei-Kuang Chen, Tai-Jan Chiu, Chien-Chia Cheng, Yueh-Fu Fang, Chia-Wei Li, Aarthi Goverdhan, Hsing-Ju Wu, Cheng-Chung Lee, Wen-Ling Wang, Jennifer Hsu, Paul Chiao, Shao-Chun Wang, Mien-Chie Hung

Faculty, Staff and Student Publications

Nuclear epidermal growth factor receptor (EGFR) has been shown to be correlated with drug resistance and a poor prognosis in patients with cancer. Previously, we have identified a tripartite nuclear localization signal (NLS) within EGFR. To comprehensively determine the functions and underlying mechanism of nuclear EGFR and its clinical implications, we aimed to explore the nuclear export signal (NES) sequence of EGFR that is responsible for interacting with the exportins. We combined in silico prediction with site-directed mutagenesis approaches and identified a putative NES motif of EGFR, which is located in amino acid residues 736-749. Mutation at leucine 747 (L747) …


Review Of Cardiovascular Risk Of Androgen Deprivation Therapy And The Influence Of Race In Men With Prostate Cancer, James Fradin, Felix J. Kim, Grace Lu-Yao, Eugene Storozynsky, William K. Kelly Apr 2023

Review Of Cardiovascular Risk Of Androgen Deprivation Therapy And The Influence Of Race In Men With Prostate Cancer, James Fradin, Felix J. Kim, Grace Lu-Yao, Eugene Storozynsky, William K. Kelly

Department of Medical Oncology Faculty Papers

Androgen deprivation therapy is the cornerstone of prostate cancer therapy. Recent studies have revealed an association between androgen deprivation therapy and cardiovascular adverse effects such as myocardial infarction and stroke. This review summarizes the available research on the cardiovascular risk of men using androgen deprivation therapy. We also discuss racial disparities surrounding both prostate cancer and cardiovascular disease, emphasizing the importance of biological/molecular and socioeconomic factors in assessing baseline risk in patients beginning androgen ablation. Based on the literature, we provide recommendations for monitoring patients who are at high risk for a cardiovascular adverse event while being treated on androgen …


Ethnic Disparities In Childhood Leukemia Survival By Border Residence: A Texas Population-Based Analysis, Maria I Castellanos, Abiodun O Oluyomi, Tiffany M Chambers, Maria M Gramatges, Lena E Winestone, Philip J Lupo, Michael E Scheurer Apr 2023

Ethnic Disparities In Childhood Leukemia Survival By Border Residence: A Texas Population-Based Analysis, Maria I Castellanos, Abiodun O Oluyomi, Tiffany M Chambers, Maria M Gramatges, Lena E Winestone, Philip J Lupo, Michael E Scheurer

Faculty, Staff and Students Publications

Background: The US-Mexico border is a medically underserved region where survival disparities have been observed in adults diagnosed and treated for various malignancies. Studies examining survival disparities among children living in this region and diagnosed with cancer are lacking. The objective of this study was to evaluate the impact of border residence on survival among children with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and living near the Texas-Mexico border at the time of their diagnosis. The authors hypothesized that this group experiences inferior survival compared with patients with childhood leukemia living in nonborder areas.

Methods: The authors conducted …


Ethnic-Specific Predictors Of Neurotoxicity Among Patients With Pediatric Acute Lymphoblastic Leukemia After High-Dose Methotrexate, Rachel D Harris, Melanie Brooke Bernhardt, Mark C Zobeck, Olga A Taylor, Maria Monica Gramatges, Eric S Schafer, Philip J Lupo, Karen R Rabin, Michael E Scheurer, Austin L Brown Apr 2023

Ethnic-Specific Predictors Of Neurotoxicity Among Patients With Pediatric Acute Lymphoblastic Leukemia After High-Dose Methotrexate, Rachel D Harris, Melanie Brooke Bernhardt, Mark C Zobeck, Olga A Taylor, Maria Monica Gramatges, Eric S Schafer, Philip J Lupo, Karen R Rabin, Michael E Scheurer, Austin L Brown

Faculty, Staff and Students Publications

High-dose methotrexate (HD-MTX; 5,000 mg/m2) is an important component of curative therapy in many treatment regimens for high-risk pediatric acute lymphoblastic leukemia (ALL). However, methotrexate therapy can result in dose-limiting neurotoxicity which may disproportionately affect Latino children. Thus, we evaluated risk factors for neurotoxicity in an ethnically diverse population of 351 patients (58.1% Latino) who received 1,183 HD-MTX infusions. Overall, thirty-five patients (10%) experienced neurotoxicity, 71% of whom were Latino. After adjusting for clinical risk factors, we found that serum creatinine elevations ≥50% of baseline were associated with a 3-fold increased odds (OR = 3.32, 95% CI: 0.98-11.21, p=0.05) for …


Update On The Role Of Feno In Asthma Management, Neveda Murugesan, Damini Saxena, Arundhati Dileep, Muhammad Adrish, Nicola A Hanania Apr 2023

Update On The Role Of Feno In Asthma Management, Neveda Murugesan, Damini Saxena, Arundhati Dileep, Muhammad Adrish, Nicola A Hanania

Faculty, Staff and Students Publications

Asthma is a heterogenous disorder characterized by presence of different phenotypes and endotypes. Up to 10% of the individuals suffer from severe asthma and are at increased risk of morbidity and mortality. Fractional exhaled nitric oxide (FeNO) is a cost-effective, point of care biomarker that is used to detect type 2 airway inflammation. Guidelines have proposed to measure FeNO as an adjunct to diagnostic evaluation in individuals with suspected asthma and to monitor airway inflammation. FeNO has lower sensitivity, suggesting that it may not be a good biomarker to rule out asthma. FeNO may also be used to predict response …


Current Barriers To Eye Care, Annika Samuelson, Bs Apr 2023

Current Barriers To Eye Care, Annika Samuelson, Bs

inSIGHT

Barriers to care penetrate all aspects within our healthcare system and ophthalmology is no exception. The World Health Organization (WHO) estimates 2.2 billion people worldwide have vision impairment, half of which are due to preventable causes and/or remain untreated. In the United States, 6 million people are reported to have visual impairment and over one million people are blind.2 The leading causes of blindness within the United States are macular degeneration, cataract, glaucoma, and diabetic retinopathy.3 Management of these diseases require access to early detection, therapeutic intervention, and follow up care at regular intervals; for example, nearly half …


Thyroid Eye Disease: Overview And Treatment, Michelle Omega, Ms Apr 2023

Thyroid Eye Disease: Overview And Treatment, Michelle Omega, Ms

inSIGHT

Your immune system consists of a guided molecular army of antibodies equipped to recognize millions of foreign enemy antigens. However, in autoimmune conditions, antibodies are produced which target the cells of your own body. This is how many autoimmune diseases begin, including thyroid eye disease.


Ophthalminute Highlight: A Look Into The Popular, Educational One-Minute Videos, Anza Rizvi, Bs Apr 2023

Ophthalminute Highlight: A Look Into The Popular, Educational One-Minute Videos, Anza Rizvi, Bs

inSIGHT

Ophthalminute is a series of one-minute videos designed to provide information on different, essential topics in ophthalmology. What separates the Ophthalminute videos from many of the other videos currently available is their unique ability to effectively and succinctly present information into a one-minute video to help viewers learn and better understand the fundamentals of ophthalmology. The videos showcase witty banter, enthusiastic energy, and stimulating visuals. Across YouTube, Twitter, and Instagram, Ophthalminute has received an astonishing over 2000 followers or subscribers and over 20,000 views!