Digital Commons Network^™

Smoking Cessation, Harm Reduction, And Biomarkers Protocols In The Phenx Toolkit: Tools For Standardized Data Collection, Laura Jean Bierut, Tabitha P Hendershot, Neal L Benowitz, K Michael Cummings, Robin J Mermelstein, Megan E Piper, Scott I Vrieze, Theodore L Wagener, Mark D Nelms, Cataia Ives, Deborah Maiese, Carol M Hamilton, Gary E Swan

2020-Current year OA Pubs

The use of standard protocols in studies supports consistent data collection, improves data quality, and facilitates cross-study analyses. Funded by the National Institutes of Health, the PhenX (consensus measures for

Modified Bare-Back Micro-Retrograde Tibial Arterial Access To Facilitate Peripheral Endovascular Therapy, Faiz Gani, Momodou L Jammeh, Mohamed A Zayed

2020-Current year OA Pubs

Patients with critical limb threatening ischemia often present with complex segmental peripheral arterial chronic total occlusions, which might not be amenable to traditional antegrade revascularization techniques. For these patients, alternative retrograde revascularization techniques could be necessary. In the present report, we describe a novel modified retrograde cannulation technique using a bare back technique that eliminates the need for conventional tibial access sheath placement and, instead, facilitates distal arterial blood sampling, blood pressure monitoring, retrograde administration of contrast agents and vasoactive substances, and a rapid-exchange strategy. This cannulation strategy can serve as part of the armamentarium in the treatment of patients …

Association And Prediction Utilizing Craniocaudal And Mediolateral Oblique View Digital Mammography And Long-Term Breast Cancer Risk, Simin Chen, Rulla M Tamimi, Graham A Colditz, Shu Jiang

2020-Current year OA Pubs

UNLABELLED: Mammographic percentage of volumetric density is an important risk factor for breast cancer. Epidemiology studies historically used film images often limited to craniocaudal (CC) views to estimate area-based breast density. More recent studies using digital mammography images typically use the averaged density between craniocaudal (CC) and mediolateral oblique (MLO) view mammography for 5- and 10-year risk prediction. The performance in using either and both mammogram views has not been well-investigated. We use 3,804 full-field digital mammograms from the Joanne Knight Breast Health Cohort (294 incident cases and 657 controls), to quantity the association between volumetric percentage of density extracted …

The Emerging Importance Of Lymphatics In Health And Disease: An Nih Workshop Report, Babak J. Mehrara, Andrea J. Radtke, Gwendalyn J. Randolph, Brianna T. Wachter, Patricia Greenwel, Ilsa I. Rovira, Zorina S. Galis, Selen C. Muratoglu

2020-Current year OA Pubs

The lymphatic system (LS) is composed of lymphoid organs and a network of vessels that transport interstitial fluid, antigens, lipids, cholesterol, immune cells, and other materials in the body. Abnormal development or malfunction of the LS has been shown to play a key role in the pathophysiology of many disease states. Thus, improved understanding of the anatomical and molecular characteristics of the LS may provide approaches for disease prevention or treatment. Recent advances harnessing single-cell technologies, clinical imaging, discovery of biomarkers, and computational tools have led to the development of strategies to study the LS. This Review summarizes the outcomes …

How Well Does Neonatal Neuroimaging Correlate With Neurodevelopmental Outcomes In Infants With Hypoxic-Ischemic Encephalopathy?, Yvonne W Wu, Sarah E Monsell, Hannah C Glass, Jessica L Wisnowski, Amit M Mathur, Robert C Mckinstry, Stefan Bluml, Fernando F Gonzalez, Bryan A Comstock, Patrick J Heagerty, Sandra E Juul

2020-Current year OA Pubs

BACKGROUND: In newborns with hypoxic-ischemic encephalopathy (HIE), the correlation between neonatal neuroimaging and the degree of neurodevelopmental impairment (NDI) is unclear.

METHODS: Infants with HIE enrolled in a randomized controlled trial underwent neonatal MRI/MR spectroscopy (MRS) using a harmonized protocol at 4-6 days of age. The severity of brain injury was measured with a validated scoring system. Using proportional odds regression, we calculated adjusted odds ratios (aOR) for the associations between MRI/MRS measures of injury and primary ordinal outcome (i.e., normal, mild NDI, moderate NDI, severe NDI, or death) at age 2 years.

RESULTS: Of 451 infants with MRI/MRS at …

Figo Staging Of Endometrial Cancer: 2023, Jonathan S. Berek, Xavier Matias-Guiu, Carien Creutzberg, Christina Fotopoulou, David Gaffney, Sean Kehoe, Kristina Lindemann, David Mutch, Nicole Concin

2020-Current year OA Pubs

INTRODUCTION: Many advances in the understanding of the pathologic and molecular features of endometrial cancer have occurred since the FIGO staging was last updated in 2009. Substantially more outcome and biological behavior data are now available regarding the several histological types. Molecular and genetic findings have accelerated since the publication of The Cancer Genome Atlas (TCGA) data and provide improved clarity on the diverse biological nature of this collection of endometrial cancers and their differing prognostic outcomes. The goals of the new staging system are to better define these prognostic groups and create substages that indicate more appropriate surgical, radiation, …

Loss Of Chromosome 3q Is A Prognostic Marker In Fusion-Negative Rhabdomyosarcoma, Carina A Dehner, Robert C Bell, Yang Cao, Kevin He, John S A Chrisinger, Amy E Armstrong, Marielle Yohe, Jack Shern, Angela C Hirbe

2020-Current year OA Pubs

PURPOSE: Soft tissue sarcomas (STS) are rare mesenchymal neoplasms that frequently show complex chromosomal aberrations such as amplifications or deletions of DNA sequences or even whole chromosomes. We recently found that gain of chromosome (chr) 8 is associated with worse overall survival (OS) in STS as a group. We therefore aimed to investigate the overall copy number profile of rhabdomyosarcoma (RMS) to evaluate for prognostic signatures.

METHODS: Fluorescence in situ hybridization (FISH) testing was performed on a cohort of STS to assess for chr8 gain. Copy number variation (CNV) data from the National Cancer Institute were analyzed to assess for …

Implementing An Interdisciplinary Procedure Curriculum, Bryce Montane, Abey Abraham, Sergio Bustamante, Tushar Vachharajani, Sabry Ayad, Jagan Devarajan, Dustin Thompson, Ran Lee, Penelope Rampersad, Brian Gage, Emily Reznicek, Chongliang Luo, Richard Wardrop

2020-Current year OA Pubs

INTRODUCTION: This curriculum was designed to improve access to procedures for our internal medicine residents.

METHODS: We created an interdisciplinary procedure course (IDPC) composed of two simulation sessions and a one-week procedural rotation supervised by multiple specialties including nephrology, cardiology, cardiothoracic anesthesiology, general anesthesiology, and interventional radiology. After the course, residents completed two surveys documenting the number of procedures and their level of confidence on a Likert scale (1 = very unconfident to 5 = very confident) prior to and after completing the curriculum.

RESULTS: Sixteen residents participated in the course from September 2021 to June 2022. The collective number …

The Spectrum Of Covid-19-Associated Chorioretinal Vasculopathy, Piero Carletti, Aaditya Shah, Christopher Bair, Christian Curran, Anthony Mai, Rachel Patel, Ramana Moorthy, Natalia Villate, Janet L Davis, Albert T Vitale, Akbar Shakoor, Lynn Hassman

2020-Current year OA Pubs

PURPOSE: Although conjunctivitis represents the most common ocular manifestation of COVID-19 infection, sight-threatening retinal involvement has been reported. Herein, we report and characterize with multimodal retinal imaging 5 cases of acute vision loss secondary to presumed chorioretinal vasculopathy temporally associated with COVID-19 infection with varying severity, visual morbidity, and treatment response, and review the available literature on the association between COVID-19 infection and retinal microvascular changes.

DESIGN: Observational case series and literature review.

METHODS: Multicenter case series of 5 patients who presented to academic centers and private offices with acute vision loss temporally associated with COVID-19 infection. A review of …

Comparison Of Bivalent And Monovalent Sars-Cov-2 Variant Vaccines: The Phase 2 Randomized Open-Label Covail Trial, Angela R Branche, Rachel M Presti, Et Al.

2020-Current year OA Pubs

Vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection wanes over time, requiring updated boosters. In a phase 2, open-label, randomized clinical trial with sequentially enrolled stages at 22 US sites, we assessed safety and immunogenicity of a second boost with monovalent or bivalent variant vaccines from mRNA and protein-based platforms targeting wild-type, Beta, Delta and Omicron BA.1 spike antigens. The primary outcome was pseudovirus neutralization titers at 50% inhibitory dilution (ID

Clusters Of Sars-Cov-2 Infection Across Six Schools For Students With Intellectual And Developmental Disabilities, Michael Gemmell, Tyler Walsh, Michael Sherby, Adwoa Imbeah, Kelly Bono, Megan Baldenweck, Christina Gurnett, Jason G Newland

2020-Current year OA Pubs

INTRODUCTION: Individuals with intellectual and developmental disabilities are at increased risk for adverse outcomes from coronavirus disease 2019. Clusters of COVID-19 infections can be used to track SARS-CoV-2 transmission. This is particularly important in environments frequently used for individuals with intellectual and developmental disabilities, such as schools. The objective of this study was to compare the number of clusters of student and staff cases identified during three distinct periods (pre-Delta, Delta, and Omicron) of the COVID-19 pandemic.

METHODS: Weekly COVID-19 testing occurred from November 23, 2020 to May 27, 2022 during three phases of the COVID-19 pandemic: pre-Delta, Delta, and …

Safety And Tolerability Of Moxidectin And Ivermectin Combination Treatments For Lymphatic Filariasis In Côte D'Ivoire: A Randomized Controlled Superiority Study, Catherine M. Bjerum, Benjamin G. Koudou, Allassane F. Ouattara, Daphne Lew, Charles W. Goss, Pascal T. Gabo, Christopher L. King, Peter U. Fischer, Gary J. Weil, Philip J. Budge

2020-Current year OA Pubs

BACKGROUND: Moxidectin is a macrocyclic lactone registered for the treatment of human onchocerciasis. The drug has a good safety profile, large volume of distribution and a long elimination half-life. This paper reports tolerability data from the first use of moxidectin in persons with Wuchereria bancrofti infection.

METHODS: In this randomized, open-label, masked-observer superiority trial, adults with Wuchereria bancrofti microfilaremia in Côte d'Ivoire were randomized to 1 of 4 treatment arms: ivermectin + albendazole (IA), moxidectin + albendazole (MoxA), ivermectin + diethylcarbamazine (DEC) + albendazole (IDA), or moxidectin + DEC + albendazole (MoxDA). As part of a larger efficacy trial, all …

Fidelity And Adherence To A Liquefied Petroleum Gas Stove And Fuel Intervention: The Multi-Country Household Air Pollution Intervention Network (Hapin) Trial, Kendra N Williams, Lindsay J Underhill, Et Al.

2020-Current year OA Pubs

BACKGROUND: Reducing household air pollution (HAP) to levels associated with health benefits requires nearly exclusive use of clean cooking fuels and abandonment of traditional biomass fuels.

METHODS: The Household Air Pollution Intervention Network (HAPIN) trial randomized 3,195 pregnant women in Guatemala, India, Peru, and Rwanda to receive a liquefied petroleum gas (LPG) stove intervention (n = 1,590), with controls expected to continue cooking with biomass fuels (n = 1,605). We assessed fidelity to intervention implementation and participant adherence to the intervention starting in pregnancy through the infant's first birthday using fuel delivery and repair records, surveys, observations, and temperature-logging stove …

Feasibility Of The Audio-Visual Assisted Therapeutic Ambience In Radiotherapy (Avatar) System For Anesthesia Avoidance In Pediatric Patients: A Multicenter Trial, Paulina M Gutkin, Stephanie M Perkins, Et Al.

2020-Current year OA Pubs

PURPOSE: The Audio-Visual Assisted Therapeutic Ambience in Radiotherapy (AVATAR) system was the first published radiation therapy (RT)-compatible system to reduce the need for pediatric anesthesia through video-based distraction. We evaluated the feasibility of AVATAR implementation and effects on anesthesia use, quality of life, and anxiety in a multicenter pediatric trial.

METHODS AND MATERIALS: Pediatric patients 3 to 10 years of age preparing to undergo RT at 10 institutions were prospectively enrolled. Children able to undergo at least 1 fraction of RT using AVATAR without anesthesia were considered successful (S). Patients requiring anesthesia for their entire treatment course were nonsuccessful (NS). …

Initial Clinical Experience Building A Dual Ct- And Mr-Guided Adaptive Radiotherapy Program, Alex T Price, Joshua P Schiff, Eric Laugeman, Matthew Schmidt, Tong Zhu, Francisco Reynoso, Yao Hao, Taeho Kim, Eric Morris, Xiaodong Zhao, Geoffrey D Hugo, Gregory Vlacich, Carl J Deselm, Pamela P Samson, Clifford G Robinson, Hyun Kim, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Our institution was the first in the world to clinically implement MR-guided adaptive radiotherapy (MRgART) in 2014. In 2021, we installed a CT-guided adaptive radiotherapy (CTgART) unit, becoming one of the first clinics in the world to build a dual-modality ART clinic. Herein we review factors that lead to the development of a high-volume dual-modality ART program and treatment census over an initial, one-year period.

MATERIALS AND METHODS: The clinical adaptive service at our institution is enabled with both MRgART (MRIdian, ViewRay, Inc, Mountain View, CA) and CTgART (ETHOS, Varian Medical Systems, Palo Alto, CA) platforms. We analyzed patient …

Novel Roles For The Transcriptional Repressor E4bp4 In Both Cardiac Physiology And Pathophysiology, Sobuj Mia, David R Rawnsley, Sumanth D Prabhu, Abhinav Diwan, Et Al.

2020-Current year OA Pubs

Circadian clocks temporally orchestrate biological processes critical for cellular/organ function. For example, the cardiomyocyte circadian clock modulates cardiac metabolism, signaling, and electrophysiology over the course of the day, such that, disruption of the clock leads to age-onset cardiomyopathy (through unknown mechanisms). Here, we report that genetic disruption of the cardiomyocyte clock results in chronic induction of the transcriptional repressor E4BP4. Importantly, E4BP4 deletion prevents age-onset cardiomyopathy following clock disruption. These studies also indicate that E4BP4 regulates both cardiac metabolism (eg, fatty acid oxidation) and electrophysiology (eg, QT interval). Collectively, these studies reveal that E4BP4 is a novel regulator of both …

Ube4a Maintains Metabolic Homeostasis And Facilitates Insulin Signaling In Vivo, Sandip Mukherjee, Andrew J Lutkewitte, Brian N Finck, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Defining the regulators of cell metabolism and signaling is essential to design new therapeutic strategies in obesity and NAFLD/NASH. E3 ubiquitin ligases control diverse cellular functions by ubiquitination-mediated regulation of protein targets, and thus their functional aberration is associated with many diseases. The E3 ligase Ube4A has been implicated in human obesity, inflammation, and cancer. However, its in vivo function is unknown, and no animal models are available to study this novel protein.

METHODS: A whole-body Ube4A knockout (UKO) mouse model was generated, and various metabolic parameters were compared in chow- and high fat diet (HFD)-fed WT and UKO …

Sleep Disturbance Among Adults With Overactive Bladder: A Cross-Sectional Survey, H H Lai, D Walker, D Elsouda, A Lockefeer, K Gallington, E D Bacci

2020-Current year OA Pubs

OBJECTIVE: To examine differences in sleep disturbance, nocturia, and depression among adults with overactive bladder (OAB) by treatment type.

METHODS: A cross-sectional survey of adults with OAB assessed sleep disturbance, nocturia, and depression using patient-reported outcome measures, including the Patient Reported Outcomes Measurement Information System (PROMIS)-29 Profile v2.1 (Sleep Disturbance and Depression domains), Lower Urinary Tract Dysfunction Research Network Symptom Index-10, and PROMIS Sleep Disturbance Short Form 8B. Treatment groups included antimuscarinics, β-3 adrenergic agonists, and no treatment. Analysis of covariance (ANCOVA) was used to test for differences in study endpoints; Bonferroni-adjusted pairwise tests (P < .05/3) were performed to compare differences in least squares means between groups.

RESULTS: One hundred participants were …

Nutritional Considerations For A New Era: A Cf Foundation Position Paper, Amanda Leonard, Marina Litvin, Et Al.

2020-Current year OA Pubs

OBJECTIVE: To provide interim advice and considerations to the CF Community around CF nutrition in the current era.

METHODS: The Cystic Fibrosis (CF) Foundation organized a multidisciplinary committee to develop a Nutrition Position Paper based on the rapidly changing nutrition landscape in CF, due in part to widespread use of cystic fibrosis transmembrane regulator highly effective modulator therapy (HEMT). Four workgroups were formed: Weight Management, Eating Behavior/Food Insecurity, Salt Homeostasis and Pancreatic Enzyme use. Each workgroup conducted their own focused review of the literature.

RESULTS: The committee summarized current understanding of issues pertaining to the four workgroup topics and provided …

Optimum Threshold Of The 4kscore For Biopsy In Men With Negative Or Indeterminate Multiparametric Magnetic Resonance Imaging, Ricardo De Almeida S Jr, Eric H Kim, Et Al.

2020-Current year OA Pubs

OBJECTIVE: The study aims to identify the optimal 4Kscore thresholds to determine the need for a prostate biopsy when multiparametric magnetic resonance imaging (MRI) (mpMRI) is negative or indeterminate.

MATERIALS AND METHODS: We analysed retrospective data from men in eight different institutions who underwent an mpMRI, 4Kscore and prostate biopsy for evaluation of prostate cancer. We selected men with a negative (PIRADS ≤2) or indeterminate (PIRADS 3) mpMRI. 4Kscore values were categorized into ranges of 1-7, 8-19, 20-32 and greater than 32. We evaluated the proportion of men with grade group 2 or higher (GG2+) cancer in groups defined by …

Personal Protective Equipment Use Among Dental Healthcare Personnel During The Coronavirus Disease 2019 (Covid-19) Pandemic And The Impact Of An Educational Video In Clinical Practice, Lucy C Vogt, Kimberly A Reske, Daniel Park, Tracey Habrock Bach, Henry B Stewart, Olivia G Arter, Daniel Stoeckel, Heidi M Steinkamp, Stephen Y Liang, Michael J Durkin, Jennie H Kwon

2020-Current year OA Pubs

OBJECTIVE: Dental healthcare personnel (DHCP) are at high risk of exposure to coronavirus disease 2019 (COVID-19). We sought to identify how DHCP changed their use of personal protective equipment (PPE) as a result of the COVID-19 pandemic, and to pilot an educational video designed to improve knowledge of proper PPE use.

DESIGN: The study comprised 2 sets of semistructured qualitative interviews.

SETTING: The study was conducted in 8 dental clinics in a Midwestern metropolitan area.

PARTICIPANTS: In total, 70 DHCP participated in the first set of interviews; 63 DHCP participated in the second set of interviews.

METHODS: In September-November 2020 …

Host Interactions Of Novel Crassvirales Species Belonging To Multiple Families Infecting Bacterial Host, Bacteroides Cellulosilyticus Wh2host Interactions Of Novel Crassvirales Species Belonging To Multiple Families Infecting Bacterial Host, Bacteroides Cellulosilyticus Wh2, Bhavya Papudeshi, Lindsay Droit, Scott A Handley, David Wang, Et Al.

2020-Current year OA Pubs

Bacteroides, the prominent bacteria in the human gut, play a crucial role in degrading complex polysaccharides. Their abundance is influenced by phages belonging to the

Comprehensive Assessment Of The Activity Level Of The Icf Using Both Capacity And Performance Measures: A Case Report, Carey L Holleran, Marghuretta D Bland, Catherine E Lang

2020-Current year OA Pubs

Individuals with neurologic conditions seek physical therapy services to improve mobility in their daily lives. While clinicians commonly track activity capacity, measurement of activity performance in daily life is an emerging yet unstandardized practice within routine clinical physical therapy. The purpose of this case report is to (1) provide an example of the structure, clinical reasoning, and implementation of both activity capacity and activity performance level assessments across an episode of outpatient physical therapy and (2) to describe how objective activity performance in daily life tracking supported the physical therapy intervention and education plan. A 42-year-old woman presented to outpatient …

Baseline Characteristics And Outcomes For People With And Without Covid-19 Diagnoses Receiving Inpatient Rehabilitation Care Across The Us In 2020-2021, Elissa J Charbonneau, Prateek Grover, Jeffery S Johns, Susan M Mcdowell, Joseph V Stillo

2020-Current year OA Pubs

OBJECTIVE: To assess sociodemographic, medical complexity, and outcomes of persons receiving care at inpatient rehabilitation facilities (IRFs) with and without a diagnosis of COVID-19.

DESIGN: A retrospective cohort study using electronic medical record (EMR) data from 138 IRFs across 34 states and Puerto Rico.

SETTING: N/A.

PARTICIPANTS: IRF EMR data for 212,663 patients discharged between 04/01/2020 and 05/31/2021 (N=212,663), of which 16,199 (COVID-19 group) had a primary or secondary COVID-19 diagnosis based upon ICD codes set (ICD-10 codes U07.1, B94.8, Z86.19, Z86.16).

MAIN OUTCOME MEASURES: Four categories: (a) sociodemographic, (b) medical complexity, (c) process, that is, standard IRF processes, and …

All-Cause Procedural Readmissions Following Transcatheter Aortic Valve Replacement, Paige Newell, Hoda Javadikasgari, Mehida Rojas-Alexandre, Sameer Hirji, Morgan Harloff, Olena Cherkasky, Siobhan Mcgurk, Alexandra Malarczyk, Pinak Shah, Ashraf Sabe, Tsuyoshi Kaneko

2020-Current year OA Pubs

OBJECTIVE: With expanding eligibility criteria, transcatheter aortic valve replacement is being performed on patients with longer life expectancy, and subsequent procedures after index transcatheter aortic valve replacement are inevitable. This study examines the incidence and outcomes of patients undergoing subsequent procedural readmissions after transcatheter aortic valve replacement.

METHODS: All patients who underwent index transcatheter aortic valve replacement and were discharged alive from January 2012 to December 2019 at a single institution were evaluated. Study end points were mortality and readmission for procedure with more than 1-day hospital stay. Effect on survival was evaluated by treating procedural readmission as a time-dependent …

Pan-Cancer Analysis Of Post-Translational Modifications Reveals Shared Patterns Of Protein Regulation, Yifat Geffen, Yizhe Song, Akshay Govindan, Yize Li, Liang-Bo Wang, Li Ding, Et Al.

2020-Current year OA Pubs

Post-translational modifications (PTMs) play key roles in regulating cell signaling and physiology in both normal and cancer cells. Advances in mass spectrometry enable high-throughput, accurate, and sensitive measurement of PTM levels to better understand their role, prevalence, and crosstalk. Here, we analyze the largest collection of proteogenomics data from 1,110 patients with PTM profiles across 11 cancer types (10 from the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium [CPTAC]). Our study reveals pan-cancer patterns of changes in protein acetylation and phosphorylation involved in hallmark cancer processes. These patterns revealed subsets of tumors, from different cancer types, including those with …

Uncharacterized And Lineage-Specific Accessory Genes Within The Proteus Mirabilis Pan-Genome Landscape, Robert F Potter, Kailun Zhang, Ben Reimler, Jamie Marino, Carol E Muenks, Kelly Alvarado, Meghan A Wallace, Lars F Westblade, Erin Mcelvania, Melanie L Yarbrough, David A Hunstad, Gautam Dantas, Carey-Ann D Burnham

2020-Current year OA Pubs

No abstract provided.

Ergosterol Distribution Controls Surface Structure Formation And Fungal Pathogenicity, Hau Lam Choy, Elizabeth A. Gaylord, Tamara L. Doering

2020-Current year OA Pubs

Ergosterol, the major sterol in fungal membranes, is critical for defining membrane fluidity and regulating cellular processes. Although ergosterol synthesis has been well defined in model yeast, little is known about sterol organization in the context of fungal pathogenesis. We identified a retrograde sterol transporter, Ysp2, in the opportunistic fungal pathogen

Pan-Cancer Proteogenomics Connects Oncogenic Drivers To Functional States, Yize Li, Song Cao, Matthew A Wyczalkowski, Yizhe Song, Erik P Storrs, Michael C Wendl, Wen-Wei Liang, Nadezhda V Terekhanova, Fernanda Martins Rodrigues, Daniel Cui Zhou, Liang-Bo Wang, Jessika Baral, Milan G Chheda, Li Ding, Et Al.

2020-Current year OA Pubs

Cancer driver events refer to key genetic aberrations that drive oncogenesis; however, their exact molecular mechanisms remain insufficiently understood. Here, our multi-omics pan-cancer analysis uncovers insights into the impacts of cancer drivers by identifying their significant cis-effects and distal trans-effects quantified at the RNA, protein, and phosphoprotein levels. Salient observations include the association of point mutations and copy-number alterations with the rewiring of protein interaction networks, and notably, most cancer genes converge toward similar molecular states denoted by sequence-based kinase activity profiles. A correlation between predicted neoantigen burden and measured T cell infiltration suggests potential vulnerabilities for immunotherapies. Patterns of …

Loss Of Stearoyl-Coa Desaturase 2 Disrupts Inflammatory Response In Macrophages, Joseph B. Lin, Amy Mora, Tzu Jui Wang, Andrea Santeford, Darksha Usmani, Marianne M. Ligon, Indira U. Mysorekar, Rajendra S. Apte

2020-Current year OA Pubs

Macrophages are innate immune cells that patrol tissues and are the first responders to detect infection. They orchestrate the host immune response in eliminating invading pathogens and the subsequent transition from inflammation to tissue repair. Macrophage dysfunction contributes to age-related pathologies, including low-grade inflammation in advanced age that is termed "inflammaging." Our laboratory has previously identified that macrophage expression of a fatty acid desaturase, stearoyl-CoA desaturase 2 (SCD2), declines with age. Herein, we delineate the precise cellular effects of SCD2 deficiency in murine macrophages. We found that deletion of