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2023

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Articles 6421 - 6450 of 27445

Full-Text Articles in Medicine and Health Sciences

Rod-Specific Downregulation Of Omega-3 Very-Long-Chain Polyunsaturated Fatty Acid Pathway In Age-Related Macular Degeneration, William C. Gordon, Marie Audrey I. Kautzmann, Bokkyoo Jun, Megan L. Cothern, Zhide Fang, Nicolas G. Bazan Sep 2023

Rod-Specific Downregulation Of Omega-3 Very-Long-Chain Polyunsaturated Fatty Acid Pathway In Age-Related Macular Degeneration, William C. Gordon, Marie Audrey I. Kautzmann, Bokkyoo Jun, Megan L. Cothern, Zhide Fang, Nicolas G. Bazan

School of Medicine Faculty Publications

Docosahexaenoic acid (DHA; 22:6) plays a key role in vision and is the precursor for very-long-chain polyunsaturated fatty acids (VLC-PUFAs). The release of 32- and 34-carbon VLC-PUFAs and DHA from sn-1 and sn-2 of phosphatidylcholine (PC) leads to the synthesis of cell-survival mediators, the elovanoids (ELVs) and neuroprotectin D1 (NPD1), respectively. Macula and periphery from age-related macular degeneration (AMD) donor retinas were assessed for the availability of DHA-related lipids by LC-MS/MS-based lipidomic analysis and MALDI-molecular imaging. We found reduced retina DHA and VLC-PUFA pathways to synthesize omega-3 ELVs from precursors that likely resulted in altered disks and photoreceptor loss. Additionally, …


Evaluation Of Field Sobriety Tests For Identifying Drivers Under The Influence Of Cannabis: A Randomized Clinical Trial, Thomas D Marcotte, Anya Umlauf, David J Grelotti, Emily G Sones, Kyle F Mastropietro, Raymond T Suhandynata, Marilyn A. Huestis, Igor Grant, Robert L Fitzgerald Sep 2023

Evaluation Of Field Sobriety Tests For Identifying Drivers Under The Influence Of Cannabis: A Randomized Clinical Trial, Thomas D Marcotte, Anya Umlauf, David J Grelotti, Emily G Sones, Kyle F Mastropietro, Raymond T Suhandynata, Marilyn A. Huestis, Igor Grant, Robert L Fitzgerald

Institute of Emerging Health Professions Faculty Papers

IMPORTANCE: With increasing medicinal and recreational cannabis legalization, there is a public health need for effective and unbiased evaluations for determining whether a driver is impaired due to Δ9-tetrahydrocannabinol (THC) exposure. Field sobriety tests (FSTs) are a key component of the gold standard law enforcement officer-based evaluations, yet controlled studies are inconclusive regarding their efficacy in detecting whether a person is under the influence of THC.

OBJECTIVE: To examine the classification accuracy of FSTs with respect to cannabis exposure and driving impairment (as determined via a driving simulation).

DESIGN, SETTING, AND PARTICIPANTS: This double-blind, placebo-controlled parallel randomized clinical trial was …


Sex-Dependent Effects Of Intestinal Microbiome Manipulation In A Mouse Model Of Alzheimer’S Disease, Harpreet Kaur, Suba Nookala, Surjeet Singh, Santhosh Mukundan, Kumi Nagamoto-Combs, Colin K. Combs Sep 2023

Sex-Dependent Effects Of Intestinal Microbiome Manipulation In A Mouse Model Of Alzheimer’S Disease, Harpreet Kaur, Suba Nookala, Surjeet Singh, Santhosh Mukundan, Kumi Nagamoto-Combs, Colin K. Combs

Biomedical Sciences Faculty Publications

Mechanisms linking intestinal bacteria and neurodegenerative diseases such as Alzheimer’s disease (AD) are still unclear. We hypothesized that intestinal dysbiosis might potentiate AD, and manipulating the microbiome to promote intestinal eubiosis and immune homeostasis may improve AD-related brain changes. This study assessed sex differences in the effects of oral probiotic, antibiotics, and synbiotic treatments in the AppNL-G-F mouse model of AD. The fecal microbiome demonstrated significant correlations between bacterial genera in AppNL-G-F mice and Aβ plaque load, gliosis, and memory performance. Female and not male AppNL-G-F mice fed probiotic but not synbiotic exhibited a decrease in Aβ plaques, microgliosis, brain …


Hla-Ii Alleles Influence Physical And Behavioral Responses To A Whey Allergen In A Transgenic Mouse Model Of Cow's Milk Allergy, Danielle L. Germundson, Suba Nookala, Nicholas A. Smith, Yassmine Warda, Kumi Nagamoto-Combs Sep 2023

Hla-Ii Alleles Influence Physical And Behavioral Responses To A Whey Allergen In A Transgenic Mouse Model Of Cow's Milk Allergy, Danielle L. Germundson, Suba Nookala, Nicholas A. Smith, Yassmine Warda, Kumi Nagamoto-Combs

Biomedical Sciences Faculty Publications

The symptoms of food allergies vary significantly between individuals, likely due to genetic determinants. In humans, allergy development is initiated by antigen-presenting cells via class II human leukocyte antigen (HLA-II). The HLA-II gene is highly polymorphic, and its allelic variance is thought to influence the susceptibility of individuals to a particular allergen. However, whether antigen presentation by different HLA-II variants contributes to symptom variation is not clear. We hypothesized that HLA-II allelic variance affects symptom phenotypes, including immediate physical reactions and delayed behavioral changes, in individuals with food hypersensitivity. To test our hypothesis, male and female mice of three transgenic …


Asymptomatic Sensitization To A Cow's Milk Protein Induces Sustained Neuroinflammation And Behavioral Changes With Chronic Allergen Exposure, Afrina Brishti, Danielle L. Germundson-Hermanson, Nicholas Smith, Angela E. Kearney, Yassmine Warda, Kumi Nagamoto-Combs Sep 2023

Asymptomatic Sensitization To A Cow's Milk Protein Induces Sustained Neuroinflammation And Behavioral Changes With Chronic Allergen Exposure, Afrina Brishti, Danielle L. Germundson-Hermanson, Nicholas Smith, Angela E. Kearney, Yassmine Warda, Kumi Nagamoto-Combs

Biomedical Sciences Faculty Publications

Mouse models of food allergy have contributed to our understanding of various aspects of the disease, including susceptibilities, symptom spectra, cellular mechanisms, and therapeutic approaches. Previously, we used a mouse model of non-anaphylactic cow’s milk allergy (CMA) and investigated sex- and strain-dependent differences in immunological, neurological, and behavioral sequelae. We showed that male C57BL/6J mice sensitized to a bovine whey protein, β-lactoglobulin (BLG; Bos d 5), exhibited anxiety- and depression-like behavior upon acute allergen challenge. Systemic levels of BLG-specific immunoglobulins, cytokines and chemokines were also elevated in the sensitized mice. Furthermore, neuroinflammation and intestinal dysbiosis were evident as the possible …


What To Expect As Children Transition To Young Adults, Melissa Ponce-Rodas Sep 2023

What To Expect As Children Transition To Young Adults, Melissa Ponce-Rodas

Lake Union Herald

No abstract provided.


Comparison Of Thickness Between Thermoformed And Printed Orthodontic Aligners, Omar Souman Sep 2023

Comparison Of Thickness Between Thermoformed And Printed Orthodontic Aligners, Omar Souman

Loma Linda University Electronic Theses, Dissertations & Projects

Introduction: The fabrication of thermoformed orthodontic aligners involves processes that irreversibly alter material properties, resulting in aligners that exhibit high variation in thickness. The non-uniform thickness can lead to unpredictable forces that can adversely affect orthodontic tooth movement. With recent technological advancements enabling the printing of orthodontic aligners, it is of clinical interest to investigate their variation of thickness.

Purpose: This study utilized Micro-Computed Tomography (Micro-CT) and Geomagic Control X metrology software to compare the thickness of thermoformed and direct printed aligners.

Materials and Methods: Intraoral scans of 13 orthodontic patients were used to generate standard tessellation …


Hla-Ii-Dependent Neuroimmune Changes In Group A Streptococcal Necrotizing Fasciitis, Ganesh Ambigapathy, Santhosh Mukundan, Kumi Nagamoto-Combs, Colin Combs, Suba Nookala Sep 2023

Hla-Ii-Dependent Neuroimmune Changes In Group A Streptococcal Necrotizing Fasciitis, Ganesh Ambigapathy, Santhosh Mukundan, Kumi Nagamoto-Combs, Colin Combs, Suba Nookala

Biomedical Sciences Faculty Publications

Streptococcus pyogenes (Group A Streptococcus, GAS) bacteria cause a spectrum of human diseases ranging from self-limiting pharyngitis and mild, uncomplicated skin infections (impetigo, erysipelas, and cellulitis) to highly morbid and rapidly invasive, life-threatening infections such as streptococcal toxic shock syndrome and necrotizing fasciitis (NF). HLA class II allelic polymorphisms are linked with differential outcomes and severity of GAS infections. The dysregulated immune response and peripheral cytokine storm elicited due to invasive GAS infections increase the risk for toxic shock and multiple organ failure in genetically susceptible individuals. We hypothesized that, while the host immune mediators regulate the immune responses against …


United We Might Stand, Divided We Will Certainly Fall!, Simon Maltais, T Sloane Guy, John M. Stulak, Lucman A. Anwer, Louis P. Perrault Sep 2023

United We Might Stand, Divided We Will Certainly Fall!, Simon Maltais, T Sloane Guy, John M. Stulak, Lucman A. Anwer, Louis P. Perrault

Department of Surgery Faculty Papers

No abstract provided.


Predictors Of Chronic Traumatic Encephalopathy In Nfl Players: A Meta Analysis Review, Eisha Vora Sep 2023

Predictors Of Chronic Traumatic Encephalopathy In Nfl Players: A Meta Analysis Review, Eisha Vora

Dissertations

Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that emerges as a result of repetitive mild traumatic brain injury and has been studied within athletes of all sports. Repetitive blows to the brain are associated with many pathological changes and an emergence of tau pathology, all of which can lead to presentation with cognitive dysfunction, behavioral changes, and further motor decline in the later stages. After passing the inclusion criteria, a meta-analysis comprising four articles was computed using Comprehensive Meta-Analysis Version 3. Two hypotheses were examined: (a) the earlier the age of exposure to football, the greater the likelihood …


Apoe Risk Disclosure: A Review Of Positive And Negative Outcome, Stacey Rowcliffe Sep 2023

Apoe Risk Disclosure: A Review Of Positive And Negative Outcome, Stacey Rowcliffe

Dissertations

Two of this century’s most significant healthcare challenges are Alzheimer’s disease and mild cognitive impairment, with 40 million people suffering from the diseases. In fact, a conservative estimate projects that both conditions will double every 20 years until 2050. Alzheimer’s disease involves memory impairment, disorientation, confusion, and various problematic behaviors. Presently, no prevention method or cure has been discovered for Alzheimer’s. Mild cognitive impairment typically includes problems with memory, language, thinking, and judgment beyond those typical of one’s age. Usually, these symptoms do not interfere with daily activities but do not improve and have been linked with a risk of …


Recursive Functional Learning In Nonfluent Aphasia, Gerald C. Imaezue Sep 2023

Recursive Functional Learning In Nonfluent Aphasia, Gerald C. Imaezue

Dissertations, Theses, and Capstone Projects

People with nonfluent aphasia (PWNA) require feedback from an external agent as well self-feedback to facilitate performance of language production tasks. The extent to which PWNA can use self-feedback alone to improve their task performance is unknown. In addition, it is argued that self-feedback may reinforce or minimize performance errors over time. To test whether either is the case, we introduce an original learning mechanism, recursive functional learning, which uses self-feedback loops to optimize recursively multiple subsystems (cognitive and linguistic subsystems) that PWNA engage during task performance. We used this mechanism to underpin a novel automated procedure we developed, recursive …


Attenuated Typicality Effect In Category-Based Inferences: Implications For Autism Spectrum Disorder, Janani Rajagopalan Sep 2023

Attenuated Typicality Effect In Category-Based Inferences: Implications For Autism Spectrum Disorder, Janani Rajagopalan

Dissertations, Theses, and Capstone Projects

Individuals diagnosed with Autism Spectrum Disorder (ASD) often encounter challenges in assimilating atypical exemplars into their categorical prototypes, a cognitive hurdle that can impact their interpretative and integrative capacities. Addressing this problem, the present research sought to develop a robust methodological approach to reduce the effect of this disparity. We examined the elements embedded within the category's internal structure, with the intention of experimentally attenuating the pronounced typicality effect, which is often exaggerated in ASD.

Across four experiments, the thesis investigated the cognitive and neural underpinnings that shape the access to the typicality gradient intrinsic to a category's structure. The …


Social And Cultural Processes That Impact Physical Activity Among South Asian Americans Managing Hypertension: A Mixed Methods Study, Sugandha Gupta Sep 2023

Social And Cultural Processes That Impact Physical Activity Among South Asian Americans Managing Hypertension: A Mixed Methods Study, Sugandha Gupta

Dissertations, Theses, and Capstone Projects

Cardiovascular disease (CVD), the number one cause of death in the U.S., disproportionately affects South Asian Americans (SAAs). Physical activity is a modifiable health behavior that can reduce cardiovascular risk. Health behaviors, such as physical activity, occur within specific social and cultural contexts and are influenced by multiple factors at multiple levels of the social ecological model. This dissertation aimed to provide a rich, culturally-informed understanding of the factors at multiple levels – individual, interpersonal, and cultural –associated with physical activity among SAAs at risk for CVD. A sequential exploratory mixed methods approach was employed to examine social and cultural …


Visualizing Dopamine Activity In Deletion Of D2 Receptors In Medium Spiny Neurons, Kunhee Lee Sep 2023

Visualizing Dopamine Activity In Deletion Of D2 Receptors In Medium Spiny Neurons, Kunhee Lee

Dissertations, Theses, and Capstone Projects

Dopamine has been implicated in motivated behaviors and reinforcement learning. In this study, we are looking at the role of dopamine in allocating efforts when obtaining reward. Using Cre recombinase genetic tool, D2 receptors in striatal indirect pathway neurons were selectively deleted, and dopamine signal was recorded in ventral striatum using fiber photometry. Behaviorally, D2 receptor deletion resulted in less effort in a Progressive Ratio (PR) paradigm shown by decreased breakpoint, number of presses, and reward pellets earned. Due to the previous evidence that dopamine positively modulates effort, we hypothesized that there would be less dopamine release in D2 deleted …


Ataxic Variant Of Guillain Barre Syndrome: A Case Report, Haris Majid Rajput, Malik Muhammad Adil, Maryam Khalil, Nayab Aslam, Zaid Waqar Sep 2023

Ataxic Variant Of Guillain Barre Syndrome: A Case Report, Haris Majid Rajput, Malik Muhammad Adil, Maryam Khalil, Nayab Aslam, Zaid Waqar

Pakistan Journal of Neurological Sciences (PJNS)

A 17-year-old girl was admitted after acute onset of unsteady gait succeeding acute gastroenteritis. Neurological examination reported normal power in all four limbs, impaired finger-nose, heel-shin tests, areflexia and ataxic gait. We eliminated other diseases with cerebellar symptoms; for example, Wernicke encephalopathy, multiple sclerosis, cerebellar vascular disease , encephalitis in the brain stem and cerebellum. Blood serum collected from the patient during the acute phase showed no anti-ganglioside antibodies. As the patient presented with evident cerebellar ataxia without muscle weakness, ophthalmoplegia or proprioceptive sensory disruption a diagnosis of ataxic form of Guillain-Barré syndrome (GBS) after nerve conduction studies. Though ataxic …


Isatin-Pyrimidine Hybrid Derivatives As Enoyl Acyl Carrier Protein Reductase (Inha) Inhibitors Against Mycobacterium Tuberculosis, Amira Khalil, Samy Mohamady, Amgad Albohy, Marwa M. Abdel-Aziz, Abdalrahman Khalifa Sep 2023

Isatin-Pyrimidine Hybrid Derivatives As Enoyl Acyl Carrier Protein Reductase (Inha) Inhibitors Against Mycobacterium Tuberculosis, Amira Khalil, Samy Mohamady, Amgad Albohy, Marwa M. Abdel-Aziz, Abdalrahman Khalifa

Pharmacy

Tuberculosis is a worldwide problem that impose a burden on the economy due to continuous development of resistant strains. The development of new antitubercular drugs is a need and can be achieved through inhibition of druggable targets. Mycobacterium tuberculosis enoyl acyl carrier protein (ACP) reductase (InhA) is an important enzyme for Mycobacterium tuberculosis survival. In this study, we report the synthesis of isatin derivatives that could treat TB through inhibition of this enzyme. Compound 4l showed IC50 value (0.6 ± 0.94 µM) similar to isoniazid but is also effective against MDR and XDR Mycobacterium tuberculosis strains (MIC of 0.48 and …


Are Patients With An International Classification Of Diseases, 10th Edition Discharge Diagnosis Code For Sepsis Different In Regard To Demographics And Outcome Variables When Comparing Those With Sepsis Only To Those Also Diagnosed With Covid-19 Or Those With A Covid-19 Diagnosis Alone?, David F. Gaieski, Jumpei Tsukuda, Parker Maddox, Michael Li Sep 2023

Are Patients With An International Classification Of Diseases, 10th Edition Discharge Diagnosis Code For Sepsis Different In Regard To Demographics And Outcome Variables When Comparing Those With Sepsis Only To Those Also Diagnosed With Covid-19 Or Those With A Covid-19 Diagnosis Alone?, David F. Gaieski, Jumpei Tsukuda, Parker Maddox, Michael Li

Department of Emergency Medicine Faculty Papers

OBJECTIVES: We analyzed whether patients with the International Classification of Diseases, 10th Edition (ICD-10) discharge diagnosis code for sepsis are different in regard to demographics and outcome variables when comparing those with sepsis only to those also diagnosed with COVID-19 or those with a COVID-19 diagnosis alone.

DESIGN: Retrospective cohort study.

SETTING: Nine hospitals in an academic health system.

PATIENTS: Patients with a final ICD-10 discharge diagnostic code for sepsis only, a diagnosis of COVID-19-only, or a final sepsis ICD-10 discharge code + a diagnosis of COVID-19 admitted to the hospital were analyzed for demographic and outcome differences between the …


Uveal Melanoma Causing Iridodialysis: Tip Of The Iceberg, Deepthi E. Kurian, Konica Singla, Carol L. Shields Sep 2023

Uveal Melanoma Causing Iridodialysis: Tip Of The Iceberg, Deepthi E. Kurian, Konica Singla, Carol L. Shields

Wills Eye Hospital Papers

No abstract provided.


Hospitalizations Among Adults With Ckd In Public Renal Specialty Practices: A Retrospective Study From Queensland, Australia, Vishal Diwan, Wendy E Hoy, Zaimin Wang, Jianzhen Zhang, Anne Cameron, Sree K Venuthurupalli, Robert G Fassett, Samuel Chan, Helen G Healy, Ken-Soon Tan, Richard Baer, Andrew J Mallett, Nicholas Gray, Murty Mantha, Roy Cherian, Clyson Mutatiri, Krishan Madhan, George Kan, Geoffrey Mitchell, Shahadat Hossain, Danielle Wu, Thin Han, Adrian Kark, Thomas Titus, Dwarakanatan Ranganathan, Ann Bonner, Sridevi Govindarajulu, Nhmrc Ckd.Cre And The Ckd.Qld Collaborative Sep 2023

Hospitalizations Among Adults With Ckd In Public Renal Specialty Practices: A Retrospective Study From Queensland, Australia, Vishal Diwan, Wendy E Hoy, Zaimin Wang, Jianzhen Zhang, Anne Cameron, Sree K Venuthurupalli, Robert G Fassett, Samuel Chan, Helen G Healy, Ken-Soon Tan, Richard Baer, Andrew J Mallett, Nicholas Gray, Murty Mantha, Roy Cherian, Clyson Mutatiri, Krishan Madhan, George Kan, Geoffrey Mitchell, Shahadat Hossain, Danielle Wu, Thin Han, Adrian Kark, Thomas Titus, Dwarakanatan Ranganathan, Ann Bonner, Sridevi Govindarajulu, Nhmrc Ckd.Cre And The Ckd.Qld Collaborative

Faculty, Staff and Student Publications

RATIONALE & OBJECTIVE: Little is known about hospital admissions in nondialysis patients with chronic kidney disease (CKD) before death or starting kidney replacement therapy (KRT).

STUDY DESIGN: Retrospective observational cohort study.

SETTING & PARTICIPANTS: Hospitalizations among 7,201 patients with CKD from 10 public renal clinics in Queensland (QLD), enrolled in the CKD.QLD registry starting in May 2011, were followed for 25,496.34 person-years until they started receiving KRT or died, or until June 30, 2018.

PREDICTORS: Demographic and clinical characteristics of patients with CKD.

OUTCOMES: Hospital admissions.

ANALYTICAL APPROACH: We evaluated the association of demographic and clinical features with hospitalizations, length …


Efficient Targeted Learning Of Heterogeneous Treatment Effects For Multiple Subgroups, Waverly Wei, Maya Petersen, Mark J Van Der Laan, Zeyu Zheng, Chong Wu, Jingshen Wang Sep 2023

Efficient Targeted Learning Of Heterogeneous Treatment Effects For Multiple Subgroups, Waverly Wei, Maya Petersen, Mark J Van Der Laan, Zeyu Zheng, Chong Wu, Jingshen Wang

Faculty, Staff and Student Publications

In biomedical science, analyzing treatment effect heterogeneity plays an essential role in assisting personalized medicine. The main goals of analyzing treatment effect heterogeneity include estimating treatment effects in clinically relevant subgroups and predicting whether a patient subpopulation might benefit from a particular treatment. Conventional approaches often evaluate the subgroup treatment effects via parametric modeling and can thus be susceptible to model mis-specifications. In this paper, we take a model-free semiparametric perspective and aim to efficiently evaluate the heterogeneous treatment effects of multiple subgroups simultaneously under the one-step targeted maximum-likelihood estimation (TMLE) framework. When the number of subgroups is large, we …


Mpla Case: How Do You Lead As A Lead Physicist?, Patricia Sansourekidou, Leonard Kim, Lee Xu, Mary Gronberg, Cassandra Stambaugh, Dongxu Wang Sep 2023

Mpla Case: How Do You Lead As A Lead Physicist?, Patricia Sansourekidou, Leonard Kim, Lee Xu, Mary Gronberg, Cassandra Stambaugh, Dongxu Wang

Faculty, Staff and Student Publications

This work of fiction is part of a case study series developed by the Medical Physics Leadership Academy (MPLA). It is intended to facilitate the discussion of the managerial and leadership challenges faced by a clinical medical physicist. In this case, a physicist David used to work in a clinic where he thrived and felt like a leader, despite not having the title. After a job change, he is now officially the "Lead Physicist" at a hospital newly affiliated with a large academic healthcare system. He believes he will be equally successful. Yet he struggles to bring about changes and …


Longitudinal Diffusion And Volumetric Kinetics Of Head And Neck Cancer Magnetic Resonance On A 15 T Mr-Linear Accelerator Hybrid System: A Prospective R-Ideal Stage 2a Imaging Biomarker Characterization/Pre-Qualification Study, Joint Head And Neck Radiation Therapy-Mri Development Cooperative, Mr-Linac Consortium Head And Neck Tumor Site Group Sep 2023

Longitudinal Diffusion And Volumetric Kinetics Of Head And Neck Cancer Magnetic Resonance On A 15 T Mr-Linear Accelerator Hybrid System: A Prospective R-Ideal Stage 2a Imaging Biomarker Characterization/Pre-Qualification Study, Joint Head And Neck Radiation Therapy-Mri Development Cooperative, Mr-Linac Consortium Head And Neck Tumor Site Group

Faculty, Staff and Student Publications

OBJECTIVES: We aim to characterize the serial quantitative apparent diffusion coefficient (ADC) changes of the target disease volume using diffusion-weighted imaging (DWI) acquired weekly during radiation therapy (RT) on a 1.5 T MR-Linac and correlate these changes with tumor response and oncologic outcomes for head and neck squamous cell carcinoma (HNSCC) patients as part of a programmatic R-IDEAL biomarker characterization effort.

METHODS: Thirty patients with HNSCC who received curative-intent RT at MD Anderson Cancer Center, were included. Baseline and weekly MRI were obtained, and various ADC parameters were extracted from the regions of interest (ROIs). Baseline and weekly ADC parameters …


Going Circular: History, Present, And Future Of Circrnas In Cancer, Giuseppina Pisignano, David C Michael, Tanvi H Visal, Radu Pirlog, Michael Ladomery, George A Calin Sep 2023

Going Circular: History, Present, And Future Of Circrnas In Cancer, Giuseppina Pisignano, David C Michael, Tanvi H Visal, Radu Pirlog, Michael Ladomery, George A Calin

Faculty, Staff and Student Publications

To date, thousands of highly abundant and conserved single-stranded RNA molecules shaped into ring structures (circRNAs) have been identified. CircRNAs are multifunctional molecules that have been shown to regulate gene expression transcriptionally and post-transcriptionally and exhibit distinct tissue- and development-specific expression patterns associated with a variety of normal and disease conditions, including cancer pathogenesis. Over the past years, due to their intrinsic stability and resistance to ribonucleases, particular attention has been drawn to their use as reliable diagnostic and prognostic biomarkers in cancer diagnosis, treatment, and prevention. However, there are some critical caveats to their utility in the clinic. Their …


Design Of A Phase Iii, Double-Blind, Randomised, Placebo-Controlled Trial Of Bi 1015550 In Patients With Progressive Pulmonary Fibrosis (Fibroneer-Ild), Toby M Maher, Shervin Assassi, Arata Azuma, Vincent Cottin, Anna-Maria Hoffmann-Vold, Michael Kreuter, Justin M Oldham, Luca Richeldi, Claudia Valenzuela, Marlies S Wijsenbeek, Carl Coeck, Christina Schlecker, Florian Voss, Daniel Wachtlin, Fernando J Martinez Sep 2023

Design Of A Phase Iii, Double-Blind, Randomised, Placebo-Controlled Trial Of Bi 1015550 In Patients With Progressive Pulmonary Fibrosis (Fibroneer-Ild), Toby M Maher, Shervin Assassi, Arata Azuma, Vincent Cottin, Anna-Maria Hoffmann-Vold, Michael Kreuter, Justin M Oldham, Luca Richeldi, Claudia Valenzuela, Marlies S Wijsenbeek, Carl Coeck, Christina Schlecker, Florian Voss, Daniel Wachtlin, Fernando J Martinez

Faculty, Staff and Student Publications

INTRODUCTION: Progressive pulmonary fibrosis (PPF) includes any diagnosis of progressive fibrotic interstitial lung disease (ILD) other than idiopathic pulmonary fibrosis (IPF). However, disease progression appears comparable between PPF and IPF, suggesting a similar underlying pathology relating to pulmonary fibrosis. Following positive results in a phase II study in IPF, this phase III study will investigate the efficacy and safety of BI 1015550 in patients with PPF (FIBRONEER-ILD).

METHODS AND ANALYSIS: In this phase III, double-blind, placebo-controlled trial, patients are being randomised 1:1:1 to receive BI 1015550 (9 mg or 18 mg) or placebo twice daily over at least 52 weeks, …


Carm1 Arginine Methyltransferase As A Therapeutic Target For Cancer, Margarida Santos, Jee Won Hwang, Mark T Bedford Sep 2023

Carm1 Arginine Methyltransferase As A Therapeutic Target For Cancer, Margarida Santos, Jee Won Hwang, Mark T Bedford

Faculty, Staff and Student Publications

Coactivator-associated arginine methyltransferase 1 (CARM1) is an arginine methyltransferase that posttranslationally modifies proteins that regulate multiple levels of RNA production and processing. Its substrates include histones, transcription factors, coregulators of transcription, and splicing factors. CARM1 is overexpressed in many different cancer types, and often promotes transcription factor programs that are co-opted as drivers of the transformed cell state, a process known as transcription factor addiction. Targeting these oncogenic transcription factor pathways is difficult but could be addressed by removing the activity of the key coactivators on which they rely. CARM1 is ubiquitously expressed, and its KO is less detrimental in …


Aerobic Exercise Alters The Melanoma Microenvironment And Modulates Erk5 S496 Phosphorylation, Hannah Savage, Sumedha Pareek, Jonghae Lee, Riccardo Ballarò, Darlan Conterno Minussi, Karma Hayek, Mumina Sadullozoda, Brooke S Lochmann, Jennifer L Mcquade, Emily C Lavoy, Enrica Marmonti, Hetal Patel, Guangyu Wang, Masaki Imanishi, Sivareddy Kotla, Jun-Ichi Abe, Keri Schadler Sep 2023

Aerobic Exercise Alters The Melanoma Microenvironment And Modulates Erk5 S496 Phosphorylation, Hannah Savage, Sumedha Pareek, Jonghae Lee, Riccardo Ballarò, Darlan Conterno Minussi, Karma Hayek, Mumina Sadullozoda, Brooke S Lochmann, Jennifer L Mcquade, Emily C Lavoy, Enrica Marmonti, Hetal Patel, Guangyu Wang, Masaki Imanishi, Sivareddy Kotla, Jun-Ichi Abe, Keri Schadler

Faculty, Staff and Student Publications

Exercise changes the tumor microenvironment by remodeling blood vessels and increasing infiltration by cytotoxic immune cells. The mechanisms driving these changes remain unclear. Herein, we demonstrate that exercise normalizes tumor vasculature and upregulates endothelial expression of VCAM1 in YUMMER 1.7 and B16F10 murine models of melanoma but differentially regulates tumor growth, hypoxia, and the immune response. We found that exercise suppressed tumor growth and increased CD8+ T-cell infiltration in YUMMER but not in B16F10 tumors. Single-cell RNA sequencing and flow cytometry revealed exercise modulated the number and phenotype of tumor-infiltrating CD8+ T cells and myeloid cells. Specifically, exercise caused a …


Cytoreductive Nephrectomy For Patients With Metastatic Sarcomatoid And/Or Rhabdoid Renal Cell Carcinoma Treated With Immune Checkpoint Therapy, Andrew W Hahn, Ritesh R Kotecha, Paul V Viscuse, Alberto C Pieretti, Andrew J Wiele, Eric Jonasch, Chung-Han Lee, Jianjun Gao, Amado J Zurita, Amishi Y Shah, Matthew T Campbell, Padmanee Sharma, Robert J Motzer, Paul Russo, Christopher G Wood, Nizar M Tannir, Martin H Voss, Jose A Karam, A Ari Hakimi, Pavlos Msaouel Sep 2023

Cytoreductive Nephrectomy For Patients With Metastatic Sarcomatoid And/Or Rhabdoid Renal Cell Carcinoma Treated With Immune Checkpoint Therapy, Andrew W Hahn, Ritesh R Kotecha, Paul V Viscuse, Alberto C Pieretti, Andrew J Wiele, Eric Jonasch, Chung-Han Lee, Jianjun Gao, Amado J Zurita, Amishi Y Shah, Matthew T Campbell, Padmanee Sharma, Robert J Motzer, Paul Russo, Christopher G Wood, Nizar M Tannir, Martin H Voss, Jose A Karam, A Ari Hakimi, Pavlos Msaouel

Faculty, Staff and Student Publications

BACKGROUND: Renal cell carcinoma (RCC) with sarcomatoid and/or rhabdoid (S/R) dedifferentiation is a highly aggressive tumor with a poor prognosis. Immune checkpoint therapy (ICT) has shown significant treatment efficacy in this subtype. There remains uncertainly regarding the role of cytoreductive nephrectomy (CN) for patients with metastatic RCC (mRCC) with S/R who received ICT.

OBJECTIVE: Here, we report the outcomes with ICT for patients with mRCC and S/R dedifferentiation by CN status.

DESIGN, SETTING, AND PARTICIPANTS: A retrospective review was conducted of 157 patients with sarcomatoid, rhabdoid, or sarcomatoid plus rhabdoid dedifferentiation who received an ICT-based regimen at two cancer centers. …


Association Between Duration Of Smoking Abstinence Before Non-Small-Cell Lung Cancer Diagnosis And Survival: A Retrospective, Pooled Analysis Of Cohort Studies, Aline F Fares, Yao Li, Mei Jiang, M Catherine Brown, Andrew C L Lam, Reenika Aggarwal, Sabine Schmid, Natasha B Leighl, Frances A Shepherd, Zhichao Wang, Nancy Diao, Angela S Wenzlaff, Juntao Xie, Takashi Kohno, Neil E Caporaso, Curtis Harris, Hongxia Ma, Matthew J Barnett, Leticia Ferro Leal, G Fernandez-Tardon, Mónica Pérez-Ríos, Michael P A Davies, Fiona Taylor, Ben Schöttker, Paul Brennan, David Zaridze, Ivana Holcatova, Jolanta Lissowska, Beata Świątkowska, Dana Mates, Milan Savic, Hermann Brenner, Angeline Andrew, Angela Cox, John K Field, Alberto Ruano-Ravina, Sanjay S Shete, Adonina Tardon, Ying Wang, Loic Le Marchand, Rui Manuel Reis, Matthew B Schabath, Chu Chen, Hongbing Shen, Brid M Ryan, Maria Teresa Landi, Kouya Shiraishi, Jie Zhang, Ann G Schwartz, Ming S Tsao, David C Christiani, Ping Yang, Rayjean J Hung, Wei Xu, Geoffrey Liu Sep 2023

Association Between Duration Of Smoking Abstinence Before Non-Small-Cell Lung Cancer Diagnosis And Survival: A Retrospective, Pooled Analysis Of Cohort Studies, Aline F Fares, Yao Li, Mei Jiang, M Catherine Brown, Andrew C L Lam, Reenika Aggarwal, Sabine Schmid, Natasha B Leighl, Frances A Shepherd, Zhichao Wang, Nancy Diao, Angela S Wenzlaff, Juntao Xie, Takashi Kohno, Neil E Caporaso, Curtis Harris, Hongxia Ma, Matthew J Barnett, Leticia Ferro Leal, G Fernandez-Tardon, Mónica Pérez-Ríos, Michael P A Davies, Fiona Taylor, Ben Schöttker, Paul Brennan, David Zaridze, Ivana Holcatova, Jolanta Lissowska, Beata Świątkowska, Dana Mates, Milan Savic, Hermann Brenner, Angeline Andrew, Angela Cox, John K Field, Alberto Ruano-Ravina, Sanjay S Shete, Adonina Tardon, Ying Wang, Loic Le Marchand, Rui Manuel Reis, Matthew B Schabath, Chu Chen, Hongbing Shen, Brid M Ryan, Maria Teresa Landi, Kouya Shiraishi, Jie Zhang, Ann G Schwartz, Ming S Tsao, David C Christiani, Ping Yang, Rayjean J Hung, Wei Xu, Geoffrey Liu

Faculty, Staff and Student Publications

BACKGROUND: The association between duration of smoking abstinence before non-small-cell lung cancer (NSCLC) diagnosis and subsequent survival can influence public health messaging delivered in lung-cancer screening. We aimed to assess whether the duration of smoking abstinence before diagnosis of NSCLC is associated with improved survival.

METHODS: In this retrospective, pooled analysis of cohort studies, we used 26 cohorts participating in Clinical Outcomes Studies of the International Lung Cancer Consortium (COS-ILCCO) at 23 hospitals. 16 (62%) were from North America, six (23%) were from Europe, three (12%) were from Asia, and one (4%) was from South America. Patients enrolled were diagnosed …


Impact Of Serial Intralesional Steroid Injections On Idiopathic Subglottic Stenosis, Matthew R Hoffman, Ankita Patro, Li-Ching Huang, Sheau-Chiann Chen, Lynn D Berry, Alexander Gelbard, David O Francis Sep 2023

Impact Of Serial Intralesional Steroid Injections On Idiopathic Subglottic Stenosis, Matthew R Hoffman, Ankita Patro, Li-Ching Huang, Sheau-Chiann Chen, Lynn D Berry, Alexander Gelbard, David O Francis

Faculty, Staff and Student Publications

OBJECTIVES: Serial intralesional steroid injection (SILSI) has been increasingly used to treat idiopathic subglottic stenosis (iSGS). Prior studies have shown effectiveness, but not in all patients. This multi-institutional study evaluates the effect of SILSI on time to recurrent operation, peak expiratory flow (PEF), and dyspnea.

METHODS: Post-hoc secondary analysis of the North American Airway Collaborative data were performed to evaluate the outcomes of iSGS patients undergoing and not undergoing SILSI. The primary outcome was time to recurrent operation, evaluated using Kaplan-Meier curves and Cox regression analysis. Secondary outcomes were change in PEF and clinical chronic obstructive pulmonary disease questionnaire (CCQ) …