Medical Specialties Commons^™

Paradoxical Effects Of Osteoprotegerin On Vascular Function: Inhibiting Inflammation While Promoting Oxidative Stress?, Nhat-Tu Le, Elizabeth A Olmsted-Davis, Jun-Ichi Abe

Faculty, Staff and Student Publications

Osteoprotegerin (OPG), also known as osteoclastogenesis inhibitory factor or tumor necrosis factor receptor superfamily member 11B, is well known as a modulator of bone remodeling. The contribution of OPG to cardiovascular disease (CVD) has been suggested, but its molecular mechanism is complex and remains unclear. In the present study, Alves-Lopes et al. (Clin. Sci. (Lond.) (2021) 135(20): https://doi.org/10.1042/CS20210643) reported the critical role of syndecan-1 (SDC-1, also known as CD138), a surface protein part of the endothelial glycocalyx, in OPG-induced vascular dysfunction. The authors found that in endothelial cells (ECs), through SDC-1, OPG increased eNOS Thr495 phosphorylation, thereby inhibiting eNOS activity. …

The Large And Small Of It: The Microbiome And Metagenomics, Austin Hopkins, Elaina Gollmar, Jessica Fernandez, Shawn Wolf, Austin Hilverding, Andrew M. Roecker

Pharmacy and Wellness Review

Metagenomics, the analysis of the microbial genome, permits scientists to understand the influences of external sources including diet, metabolism and antibiotics on the human microbiome. Research has revealed the possibility of a core symbiosis between humans and bacteria. The main role of the human microbiome is to aid in digestion, but identified ancillary roles include immunologic homeostasis and infection prevention. Quantifying the composition and variability of the microbiome will help lead to future treatments or preventive strategies against unhealthy change. A variety of methods may be used to define the microbiome, and 16S amplicon sequencing is primarily utilized today. Probiotics …

Prmt5 Interacting Partners And Substrates In Oligodendrocyte Lineage Cells, David K. Dansu, Jialiang Liang, Ipek Selcen, Haiyan Zheng, Dirk F. Moore, Patricia Casaccia

Advanced Science Research Center

The protein arginine methyl transferase PRMT5 is an enzyme expressed in oligodendrocyte lineage cells and responsible for the symmetric methylation of arginine residues on histone tails. Previous work from our laboratory identified PRMT5 as critical for myelination, due to its transcriptional regulation of genes involved in survival and early stages of differentiation. However, besides its nuclear localization, PRMT5 is found at high levels in the cytoplasm of several cell types, including oligodendrocyte progenitor cells (OPCs) and yet, its interacting partners in this lineage, remain elusive. By using mass spectrometry on protein eluates from extracts generated from primary oligodendrocyte lineage cells …

Proteomic Profiling Based Classification Of Cll Provides Prognostication For Modern Therapy And Identifies Novel Therapeutic Targets, Ti'ara L Griffen, Fieke W Hoff, Yihua Qiu, James W Lillard, Alessandra Ferrajoli, Philip Thompson, Endurance Toro, Kevin Ruiz, Jan Burger, William Wierda, Steven M Kornblau

Faculty, Staff and Student Publications

Protein expression for 384 total and post-translationally modified proteins was assessed in 871 CLL and MSBL patients and was integrated with clinical data to identify strategies for improving diagnostics and therapy, making this the largest CLL proteomics study to date. Proteomics identified six recurrent signatures that were highly prognostic of survival and time to first or second treatment at three levels: individual proteins, when grouped into 40 functionally related groups (PFGs), and systemically in signatures (SGs). A novel SG characterized by hairy cell leukemia like proteomics but poor therapy response was discovered. SG membership superseded other prognostic factors (Rai Staging, …

Gut-Derived Butyrate Suppresses Ocular Surface Inflammation, Laura Schaefer, Humberto Hernandez, Rosalind A Coats, Zhiyuan Yu, Stephen C Pflugfelder, Robert A Britton, Cintia S De Paiva

Faculty, Staff and Students Publications

Dry eye is a common ocular inflammatory disorder characterized by tear film instability and reduced tear production. There is increasing evidence that homeostasis of the ocular surface is impacted by the intestinal microbiome. We are interested in investigating the potential role of microbially produced small molecules in mediating the interaction between the intestinal microbiota and the ocular surface. One such molecule is butyrate, a short-chain fatty acid (SCFA) produced by certain members of the gut microbiota through fermentation of dietary fiber. Here we show that SCFA transporter SLC5A8 is expressed in vivo in murine conjunctival and corneal epithelium. Pre-treatment of …

Considerations For The Use Of Phage Therapy In Clinical Practice, Gina A Suh, Thomas P Lodise, Pranita D Tamma, Jane M Knisely, Jose Alexander, Saima Aslam, Karen D Barton, Erica Bizzell, Katherine M C Totten, Joseph L Campbell, Benjamin K Chan, Scott A Cunningham, Katherine E Goodman, Kerryl E Greenwood-Quaintance, Anthony D Harris, Shayla Hesse, Anthony Maresso, Veronique Nussenblatt, David Pride, Michael J Rybak, Zoe Sund, David Van Duin, Daria Van Tyne, Robin Patel

Faculty, Staff and Students Publications

Increasing antimicrobial resistance and medical device-related infections have led to a renewed interest in phage therapy as an alternative or adjunct to conventional antimicrobials. Expanded access and compassionate use cases have risen exponentially but have varied widely in approach, methodology, and clinical situations in which phage therapy might be considered. Large gaps in knowledge contribute to heterogeneity in approach and lack of consensus in many important clinical areas. The Antibacterial Resistance Leadership Group (ARLG) has convened a panel of experts in phage therapy, clinical microbiology, infectious diseases, and pharmacology, who worked with regulatory experts and a funding agency to identify …

Synergy Of Venetoclax And 8-Chloro-Adenosine In Aml: The Interplay Of Rrna Inhibition And Fatty Acid Metabolism, Dinh Hoa Hoang, Corey Morales, Ivan Rodriguez Rodriguez, Melissa Valerio, Jiamin Guo, Min-Hsuan Chen, Xiwei Wu, David Horne, Varsha Gandhi, Lisa S Chen, Bin Zhang, Vinod Pullarkat, Steven T Rosen, Guido Marcucci, Ralf Buettner, Le Xuan Truong Nguyen

Faculty, Staff and Student Publications

It is known that 8-chloro-adenosine (8-Cl-Ado) is a novel RNA-directed nucleoside analog that targets leukemic stem cells (LSCs). In a phase I clinical trial with 8-Cl-Ado in patients with refractory or relapsed (R/R) AML, we observed encouraging but short-lived clinical responses, likely due to intrinsic mechanisms of LSC resistance. LSC homeostasis depends on amino acid-driven and/or fatty acid oxidation (FAO)-driven oxidative phosphorylation (OXPHOS) for survival. We recently reported that 8-Cl-Ado and the BCL-2-selective inhibitor venetoclax (VEN) synergistically inhibit FAO and OXPHOS in LSCs, thereby suppressing acute myeloid leukemia (AML) growth in vitro and in vivo. Herein, we report that 8-Cl-Ado …

A Novel Proton-Integrating Radiography System Design Using A Monolithic Scintillator Detector: Experimental Studies, Chinmay D Darne, Daniel G Robertson, Fahed Alsanea, Charles-Antoine Collins-Fekete, Sam Beddar

Faculty, Staff and Student Publications

Research on proton-based imaging systems aims to improve treatment planning, internal anatomy visualization, and patient alignment for proton radiotherapy. The purpose of this study was to demonstrate a new proton radiography system design consisting of a monolithic plastic scintillator volume and two optical cameras for use with scanning proton pencil beams. Unlike the thin scintillating plates currently used for proton radiography, the plastic scintillator volume (20 × 20 × 20 cm

Triglyceride-Rich Lipoproteins, Apolipoprotein C-Iii, Angiopoietin-Like Protein 3, And Cardiovascular Events In Older Adults: Atherosclerosis Risk In Communities (Aric) Study, Aliza Hussain, Caroline Sun, Elizabeth Selvin, Vijay Nambi, Josef Coresh, Xiaoming Jia, Christie M Ballantyne, Ron C Hoogeveen

Faculty, Staff and Students Publications

AIMS: Despite statin and antihypertensive therapies, older Americans have high atherosclerotic cardiovascular disease (ASCVD) risk. Novel measures of triglyceride-rich lipoproteins, low-density lipoprotein triglycerides (LDL-TG), and remnant-like particle cholesterol (RLP-C), are associated with ASCVD in middle-aged adults. Polymorphisms in genes encoding angiopoietin-related protein 3 (ANGPTL3) and apolipoprotein C-III (apoC-III), two proteins involved in triglyceride catabolism, are associated with increased risk for hypertriglyceridaemia and ASCVD and are potential therapeutic targets. We examined associations of LDL-TG, RLP-C, apoC-III, and ANGPTL3 levels with ASCVD events in older adults in the Atherosclerosis Risk in Communities (ARIC) study.

METHODS AND RESULTS: In 6359 participants (mean age …

Blood-Based Biomarker Panel For Personalized Lung Cancer Risk Assessment, Johannes F Fahrmann, Tracey Marsh, Ehsan Irajizad, Nikul Patel, Eunice Murage, Jody Vykoukal, Jennifer B Dennison, Kim-Anh Do, Edwin Ostrin, Margaret R Spitz, Stephen Lam, Sanjay Shete, Rafael Meza, Martin C Tammemägi, Ziding Feng, Samir M Hanash

Faculty, Staff and Student Publications

Purpose: To investigate whether a panel of circulating protein biomarkers would improve risk assessment for lung cancer screening in combination with a risk model on the basis of participant characteristics.

Methods: A blinded validation study was performed using prostate lung colorectal ovarian (PLCO) Cancer Screening Trial data and biospecimens to evaluate the performance of a four-marker protein panel (4MP) consisting of the precursor form of surfactant protein B, cancer antigen 125, carcinoembryonic antigen, and cytokeratin-19 fragment in combination with a lung cancer risk prediction model (PLCOm2012) compared with current US Preventive Services Task Force (USPSTF) screening criteria. The 4MP was …

Measurable Residual Disease Response And Prognosis In Treatment-Naïve Acute Myeloid Leukemia With Venetoclax And Azacitidine, Keith W Pratz, Brian A Jonas, Vinod Pullarkat, Christian Recher, Andre C Schuh, Michael J Thirman, Jacqueline S Garcia, Courtney D Dinardo, Vladimir Vorobyev, Nicola S Fracchiolla, Su-Peng Yeh, Jun Ho Jang, Muhit Ozcan, Kazuhito Yamamoto, Arpad Illes, Ying Zhou, Monique Dail, Brenda Chyla, Jalaja Potluri, Hartmut Döhner

Faculty, Staff and Student Publications

PURPOSE: There is limited evidence on the clinical utility of monitoring measurable residual disease (MRD) in patients with acute myeloid leukemia treated with lower-intensity therapy. Herein, we explored the outcomes of patients treated with venetoclax and azacitidine who achieved composite complete remission (CRc; complete remission + complete remission with incomplete hematologic recovery) and MRD < 10

METHODS: The patients included in this report were treated with venetoclax and azacitidine. Bone marrow aspirate samples for multiparametric flow cytometry assessments were collected for central analysis at baseline, end of cycle 1, and every three cycles thereafter. MRD-negative response was defined as < 1 residual blast per 1,000 leukocytes (< 10

RESULTS: One hundred …

Optimal Iron Content In Ready-To-Use Therapeutic Foods For The Treatment Of Severe Acute Malnutrition In The Community Settings: A Protocol For The Systematic Review And Meta-Analysis, Aamer Imdad, Melissa François, Fanny F. Chen, Abigail Smith, Olivia Tsistinas, Emily Tanner Smith, Jai K. Das, Zulfiqar Ahmed Bhutta

Department of Paediatrics and Child Health

Introduction: The current standard of care for children with severe acute malnutrition (SAM) involves using ready-to-use therapeutic food (RUTF) to promote growth; however, the precise formulation to achieve optimal recovery remains unclear. Emerging research suggests that alternative RUTF formulations may be more effective in correcting SAM-related complications such as anaemia and iron deficiency. This systematic review commissioned by the WHO aims to synthesise the most recent research on the iron content in RUTF and related products in the community-based treatment of uncomplicated severe malnutrition in children aged 6 months and older.
Methods and analysis: We will search multiple electronic databases. …

Dpo: Diffuse Pulmonary Ossification - A Diagnostic Challenge, Gaetano Rea, Giuliana Giacobbe, Danila Caroppo, Silvia Iovine, Roberta Lieto, Marialuisa Bocchino, Tullio Valente, Angelantonio Maglio, Alessandro Vatrella

Translational Medicine @ UniSa

Diffuse pulmonary ossification (DPO) is a rare condition of DLD (diffuse lung disease) characterized by the presence of metaplastic ectopic bone in the lungs and is less frequent in patients without a clear background of lung diseases. DPO is characterized by very small calcific nodules, often with bone mature located in both lungs and often in peripheral areas of the lungs. Two patterns of DPO have been recognized dendriform and nodular. The dendriform type is less common and is characterized by a coral-like network of bone spiculae along the alveolar septa and is often related to interstitial fibrosis or chronic …

Analysis Of The Circrna And T-Ucr Populations Identifies Convergent Pathways In Mouse And Human Models Of Rett Syndrome, Edilene Siqueira, Aida Obiols-Guardia, Olga C Jorge-Torres, Cristina Oliveira-Mateos, Marta Soler, Deepthi Ramesh-Kumar, Fernando Setién, Daniëlle Van Rossum, Ainhoa Pascual-Alonso, Clara Xiol, Cristina Ivan, Masayoshi Shimizu, Judith Armstrong, George A Calin, R Jeroen Pasterkamp, Manel Esteller, Sonia Guil

Faculty, Staff and Student Publications

Noncoding RNAs play regulatory roles in physiopathology, but their involvement in neurodevelopmental diseases is poorly understood. Rett syndrome is a severe, progressive neurodevelopmental disorder linked to loss-of-function mutations of the MeCP2 gene for which no cure is yet available. Analysis of the noncoding RNA profile corresponding to the brain-abundant circular RNA (circRNA) and transcribed-ultraconserved region (T-UCR) populations in a mouse model of the disease reveals widespread dysregulation and enrichment in glutamatergic excitatory signaling and microtubule cytoskeleton pathways of the corresponding host genes. Proteomic analysis of hippocampal samples from affected individuals confirms abnormal levels of several cytoskeleton-related proteins together with key …

Identification Of The Global Mir-130a Targetome Reveals A Role For Tbl1xr1 In Hematopoietic Stem Cell Self-Renewal And T(8; 21) Aml, Gabriela Krivdova, Veronique Voisin, Erwin M Schoof, Sajid A Marhon, Alex Murison, Jessica L Mcleod, Martino M Gabra, Andy G X Zeng, Stefan Aigner, Brian A Yee, Alexander A Shishkin, Eric L Van Nostrand, Karin G Hermans, Aaron C Trotman-Grant, Nathan Mbong, James A Kennedy, Olga I Gan, Elvin Wagenblast, Daniel D De Carvalho, Leonardo Salmena, Mark D Minden, Gary D Bader, Gene W Yeo, John E Dick, Eric R Lechman

Faculty, Staff and Students Publications

Gene expression profiling and proteome analysis of normal and malignant hematopoietic stem cells (HSCs) point to shared core stemness properties. However, discordance between mRNA and protein signatures highlights an important role for post-transcriptional regulation by microRNAs (miRNAs) in governing this critical nexus. Here, we identify miR-130a as a regulator of HSC self-renewal and differentiation. Enforced expression of miR-130a impairs B lymphoid differentiation and expands long-term HSCs. Integration of protein mass spectrometry and chimeric AGO2 crosslinking and immunoprecipitation (CLIP) identifies TBL1XR1 as a primary miR-130a target, whose loss of function phenocopies miR-130a overexpression. Moreover, we report that miR-130a is highly expressed …

Defining The Mammalian Coactivation Of Hepatic 12-H Clock And Lipid Metabolism, Huan Meng, Naomi M Gonzales, Sung Yun Jung, Yue Lu, Nagireddy Putluri, Bokai Zhu, Clifford C Dacso, David M Lonard, Bert W O'Malley

Faculty, Staff and Students Publications

The 12-h clock coordinates lipid homeostasis, energy metabolism, and stress rhythms via the transcriptional regulator XBP1. However, the biochemical and physiological bases for integrated control of the 12-h clock and diverse metabolic pathways remain unclear. Here, we show that steroid receptor coactivator SRC-3 coactivates XBP1 transcription and regulates hepatic 12-h cistrome and gene rhythmicity. Mice lacking SRC-3 show abnormal 12-h rhythms in hepatic transcription, metabolic functions, systemic energetics, and rate-limiting lipid metabolic processes, including triglyceride, phospholipid, and cardiolipin pathways. Notably, 12-h clock coactivation is not only preserved, with its cistromic activation priming ahead of the zeitgeber cue of light, but …

Soy Formula Is Not Estrogenic And Does Not Result In Reproductive Toxicity In Male Piglets: Results From A Controlled Feeding Study, Martin J.J. Ronis, Horacio Gomez‐Acevedo, Kartik Shankar, Leah Hennings, Neha Sharma, Michael L. Blackburn, Isabelle Miousse, Harry Dawson, Celine Chen, Kelly E. Mercer, Thomas M. Badger

School of Graduate Studies Faculty Publications

Soy infant formula which is fed to over half a million infants per year contains isoflavones such as genistein, which have been shown to be estrogenic at high concentrations. The developing testis is sensitive to estrogens, raising concern that the use of soy formulas may result in male reproductive toxicity. In the current study, male White‐Dutch Landrace piglets received either sow milk (Sow), or were provided milk formula (Milk), soy formula (Soy), milk formula supplemented with 17‐beta‐estradiol (2 mg/kg/d) (M + E2) or supplemented with genistein (84 mg/L of diet; (M + G) from postnatal day 2 until day 21. …

Depletion Of Transmembrane Mucin 4 (Muc4) Alters Intestinal Homeostasis In A Genetically Engineered Mouse Model Of Colorectal Cancer, Ramesh Pothuraju, Priya Pai, Sanjib Chaudhary, Jawed A Siddiqui, Jesse L Cox, Sukhwinder Kaur, Satyanarayana Rachagani, Hemant K Roy, Michael Bouvet, Surinder K Batra

Faculty, Staff and Students Publications

Mucins are components of the mucus layer overlying the intestinal epithelial cells, which maintains physiological homeostasis. Altered mucin expression is associated with disease progression. Expression of MUC4 decreases in colorectal cancer (CRC); however, its functional role and implications in the intestinal pathology in CRC are not studied well. Therefore, we generated a genetically engineered Muc4 knockout (Muc4-/-) CRC mouse model by crossing with Muc4-/- and Apc^flox/flox mice in the presence of colon-specific inducible Cre. We observed that deficiency of Muc4 results in an increased number of macroscopic tumors in the colon and rectal region and leads to poor survival. …

Increased Dna Methylation, Cellular Senescence And Premature Epigenetic Aging In Guinea Pigs And Humans With Tuberculosis, Carly A Bobak, Abhimanyu, Harini Natarajan, Tanmay Gandhi, Sandra L Grimm, Tomoki Nishiguchi, Kent Koster, Santiago Carrero Longlax, Qiniso Dlamini, Jacquiline Kahari, Godwin Mtetwa, Jeffrey D Cirillo, James O'Malley, Jane E Hill, Cristian Coarfa, Andrew R Dinardo

Faculty, Staff and Students Publications

Background: Tuberculosis (TB) is the archetypical chronic infection, with patients having months of symptoms before diagnosis. In the two years after successful therapy, survivors of TB have a three-fold increased risk of death.

Methods: Guinea pigs were infected with Mycobacterium tuberculosis (Mtb) for 45 days, followed by RRBS DNA methylation analysis. In humans, network analysis of differentially expressed genes across three TB cohorts were visualized at the pathway-level. Serum levels of inflammation were measured by ELISA. Horvath (DNA methylation) and RNA-seq biological clocks were used to investigate shifts in chronological age among humans with TB.

Results: Guinea pigs …

Ezh2 And Endometrial Cancer Development: Insights From A Mouse Model, Xin Fang, Nan Ni, Xiaofang Wang, Yanan Tian, Ivan Ivanov, Monique Rijnkels, Kayla J Bayless, John P Lydon, Qinglei Li

Faculty, Staff and Students Publications

Enhancer of zeste homolog 2 (EZH2), a core component of polycomb repressive complex 2, plays an important role in cancer development. As both oncogenic and tumor suppressive functions of EZH2 have been documented in the literature, the objective of this study is to determine the impact of Ezh2 deletion on the development and progression of endometrial cancer induced by inactivation of phosphatase and tensin homolog (PTEN), a tumor suppressor gene frequently dysregulated in endometrial cancer patients. To this end, we created mice harboring uterine deletion of both Ezh2 and Pten using Cre recombinase driven by the progesterone receptor …

A Red Fluorescent Protein With Improved Monomericity Enables Ratiometric Voltage Imaging With Asap3, Benjamin B Kim, Haodi Wu, Yukun A Hao, Michael Pan, Mariya Chavarha, Yufeng Zhao, Michael Westberg, François St-Pierre, Joseph C Wu, Michael Z Lin

Faculty, Staff and Students Publications

A ratiometric genetically encoded voltage indicator (GEVI) would be desirable for tracking transmembrane voltage changes in the presence of sample motion. We performed combinatorial multi-site mutagenesis on a cyan-excitable red fluorescent protein to create the bright and monomeric mCyRFP3, which proved to be uniquely non-perturbing when fused to the GEVI ASAP3. The green/red ratio from ASAP3-mCyRFP3 (ASAP3-R3) reported voltage while correcting for motion artifacts, allowing the visualization of membrane voltage changes in contracting cardiomyocytes and throughout the cell cycle of motile cells.

Lipid Based Nanoparticles As A Novel Treatment Modality For Hepatocellular Carcinoma: A Comprehensive Review On Targeting And Recent Advances, Khaled Mahmoud, Shady Swidan, Mohamed A. El-Nabarawi, Mahmoud H. Teaima

Pharmacy

Liver cancer is considered one of the deadliest diseases with one of the highest disease burdens worldwide. Among the different types of liver cancer, hepatocellular carcinoma is considered to be the most common type. Multiple conventional approaches are being used in treating hepatocellular carcinoma. Focusing on drug treatment, regular agents in conventional forms fail to achieve the intended clinical outcomes. In order to improve the treatment outcomes, utilizing nanoparticles—specifically lipid based nanoparticles—are considered to be one of the most promising approaches being set in motion. Multiple forms of lipid based nanoparticles exist including liposomes, solid lipid nanoparticles, nanostructured lipid carriers, …

Design And Development Of Software With A Graphical User Interface To Display And Convert Multiple Microscopic Histology Images, Sayed Ahmadreza Razian, Majid Jadidi, Alexey Kamenskiy

UNO Student Research and Creative Activity Fair

Histological images are widely used to assess the microscopic anatomy of biological tissues. Recent advancements in image analysis allow the identification of structural features on histological sections that can help advance medical device development, brain and cancer research, drug discovery, vascular mechanobiology, and many other fields. Histological slide scanners create images in SVS and TIFF formats that were designed to archive image blocks and high-resolution textual information. Because these formats were primarily intended for storage, they are often not compatible with conventional image analysis software and require conversion before they can be used in research. We have developed a user-friendly …

Breaks In Longitudinal Elastic Fibers Of Human Femoropopliteal Arteries, Elham Zamani

UNO Student Research and Creative Activity Fair

Breaks in Longitudinal Elastic Fibers of Human Femoropopliteal Arteries

Elham Zamani1, Majid Jadidi1

1 Department of Biomechanics, University of Nebraska Omaha, Omaha, NE

Introduction: Elastin is a major protein in the body with half-life >50 years. It is thought that elastic fibers are formed before the postnatal period. In the femoropopliteal artery (FPA), the main artery in the leg, longitudinal elastic fibers are present in External Elastic Lamina (EEL). Our team has studied more than 1000 cadaveric human FPA and has noticed that there are big breaks in their longitudinal elastic fibers in some subjects. Our goal in this work …

Pufa Ω-3 And Ω-6 Biomarkers And Sleep: A Pooled Analysis Of Cohort Studies On Behalf Of The Fatty Acids And Outcomes Research Consortium (Force), Rachel A Murphy, Nathan Tintle, William S Harris, Maryam Darvishian, Matti Marklund, Jyrki K Virtanen, Sari Hantunen, Vanessa D De Mello, Jaakko Tuomilehto, Jaana Lindström, Matthew A Bolt, Ingeborg A Brouwer, Alexis C Wood, Mackenzie Senn, Susan Redline, Michael Y Tsai, Vilmundur Gudnason, Gudny Eiriksdottir, Eva Lindberg, Aladdin H Shadyab, Buyun Liu, Mercedes Carnethon, Matti Uusitupa, Luc Djousse, Ulf Risérus, Lars Lind, Rob M Van Dam, Woon-Puay Koh, Peilin Shi, David Siscovick, Rozenn N Lemaitre, Dariush Mozaffarian

Children’s Nutrition Research Center Staff Publications

BACKGROUND: n-3 and n-6 PUFAs have physiologic roles in sleep processes, but little is known regarding circulating n-3 and n-6 PUFA and sleep parameters.

OBJECTIVES: We sought to assess associations between biomarkers of n-3 and n-6 PUFA intake with self-reported sleep duration and difficulty falling sleeping in the Fatty Acids and Outcome Research Consortium.

METHODS: Harmonized, de novo, individual-level analyses were performed and pooled across 12 cohorts. Participants were 35-96 y old and from 5 nations. Circulating measures included α-linolenic acid (ALA), EPA, docosapentaenoic acid (DPA), DHA, EPA + DPA + DHA, linoleic acid, and arachidonic acid. Sleep duration (10 …

Chromosomal Imbalances Detected Via Rna-Sequencing In 28 Cancers, Zuhal Ozcan, Francis A San Lucas, Justin W Wong, Kyle Chang, Konrad H Stopsack, Jerry Fowler, Yasminka A Jakubek, Paul Scheet

Faculty, Staff and Student Publications

Motivation: RNA-sequencing (RNA-seq) of tumor tissue is typically only used to measure gene expression. Here, we present a statistical approach that leverages existing RNA-seq data to also detect somatic copy number alterations (SCNAs), a pervasive phenomenon in human cancers, without a need to sequence the corresponding DNA.

Results: We present an analysis of 4942 participant samples from 28 cancers in The Cancer Genome Atlas (TCGA), demonstrating robust detection of SCNAs from RNA-seq. Using genotype imputation and haplotype information, our RNA-based method had a median sensitivity of 85% to detect SCNAs defined by DNA analysis, at high specificity (∼95%). As an …

Prognostic Impact Of High Baseline Stromal Tumor-Infiltrating Lymphocytes In The Absence Of Pathologic Complete Response In Early-Stage Triple-Negative Breast Cancer, Nour Abuhadra, Ryan Sun, Jennifer K Litton, Gaiane M Rauch, Clinton Yam, Jeffrey T Chang, Sahil Seth, Roland Bassett, Bora Lim, Alastair M Thompson, Elizabeth Mittendorf, Beatriz E Adrada, Senthil Damodaran, Jason White, Elizabeth Ravenberg, Rosalind Candelaria, Banu Arun, Naoto T Ueno, Lumarie Santiago, Sadia Saleem, Sausan Abouharb, Rashmi K Murthy, Nuhad Ibrahim, Aysegul A Sahin, Vicente Valero, William Fraser Symmans, Debu Tripathy, Stacy Moulder, Lei Huo

Faculty, Staff and Student Publications

High stromal tumor-infiltrating lymphocytes (sTILs) are associated with an improved pathologic complete response (pCR) and survival in triple-negative breast cancer (TNBC). We hypothesized that high baseline sTILs would have a favorable prognostic impact in TNBC patients without a pCR after neoadjuvant chemotherapy (NACT). In this prospective NACT study, pretreatment biopsies from 318 patients with early-stage TNBC were evaluated for sTILs. Recursive partitioning analysis (RPA) was applied to search for the sTIL cutoff best associated with a pCR. With ≥20% sTILs identified as the optimal cutoff, 33% patients had high sTILs (pCR rate 64%) and 67% had low sTILs (pCR rate …

Covid-19 In Cns And Pns: Basic And Clinical Focus On The Mechanisms Of Infection And New Tools For The Therapeutic Approach, Jorge Matias-Guiu, Jordi A. Matias-Guiu, Carmen Garrido, Genaro Pimienta, Patricio F. Reyes, Abdul Mannan Baig, Ulises Gomez-Pinedo

Department of Biological & Biomedical Sciences

No abstract provided.

The Impact Of Radiation Dose To Heart Substructures On Major Coronary Events And Patient Survival After Chemoradiation Therapy For Esophageal Cancer, Xin Wang, Nicolas L Palaskas, Brian P Hobbs, Jun-Ichi Abe, Kevin T Nead, Syed Wamique Yusuf, Joerg Hermann, Anita Deswal, Steven H Lin

Faculty, Staff and Student Publications

Simple Summary

Whether it is necessary to evaluate the radiation exposure of cardiac substructures when making radiotherapy plans is one of the current research hotspots. In this cohort study of 355 patients with esophageal cancer, the radiation dose to key coronary substructures such as the left anterior descending artery V30_Gy and mean left main coronary artery was closely associated with major coronary events and overall patient survival, and showed better predictive value than the mean heart dose or heart V30_Gy recommended by current guidelines. Our findings suggest that, in addition to the whole heart, key coronary substructures should …

Conventional Therapies Deplete Brain-Infiltrating Adaptive Immune Cells In A Mouse Model Of Group 3 Medulloblastoma Implicating Myeloid Cells As Favorable Immunotherapy Targets, Zahra Abbas, Courtney George, Mathew Ancliffe, Meegan Howlett, Anya C. Jones, Mani Kuchibhotla, Robert J. Wechsler-Reya, Nicholas G. Gottardo, Raelene Endersby

Research outputs 2022 to 2026

Medulloblastoma is the most common childhood brain cancer. Mainstay treatments of radiation and chemotherapy have not changed in decades and new treatment approaches are crucial for the improvement of clinical outcomes. To date, immunotherapies for medulloblastoma have been unsuccessful, and studies investigating the immune microenvironment of the disease and the impact of current therapies are limited. Preclinical models that recapitulate both the disease and immune environment are essential for understanding immune-tumor interactions and to aid the identification of new and effective immunotherapies. Using an immune-competent mouse model of aggressive Myc-driven medulloblastoma, we characterized the brain immune microenvironment and changes induced …