Digital Commons Network^™

Edge-Centric Analysis Of Stroke Patients: An Alternative Approach For Biomarkers Of Lesion Recovery, Sebastian Idesis, Joshua Faskowitz, Richard F Betzel, Maurizio Corbetta, Olaf Sporns, Gustavo Deco

2020-Current year OA Pubs

Most neuroimaging studies of post-stroke recovery rely on analyses derived from standard node-centric functional connectivity to map the distributed effects in stroke patients. Here, given the importance of nonlocal and diffuse damage, we use an edge-centric approach to functional connectivity in order to provide an alternative description of the effects of this disorder. These techniques allow for the rendering of metrics such as normalized entropy, which describes the diversity of edge communities at each node. Moreover, the approach enables the identification of high amplitude co-fluctuations in fMRI time series. We found that normalized entropy is associated with stroke lesion severity …

Neonatal Motor Functional Connectivity And Motor Outcomes At Age Two Years In Very Preterm Children With And Without High-Grade Brain Injury, Peppar E P Cyr, Rachel E Lean, Jeanette K Kenley, Sydney Kaplan, Dominique E Meyer, Jeffery J Neil, Dimitrios Alexopoulos, Rebecca G Brady, Joshua S Shimony, Thomas L Rodebaugh, Cynthia E Rogers, Christopher D Smyser

2020-Current year OA Pubs

Preterm-born children have high rates of motor impairments, but mechanisms for early identification remain limited. We hypothesized that neonatal motor system functional connectivity (FC) would relate to motor outcomes at age two years; currently, this relationship is not yet well-described in very preterm (VPT; born <32 weeks' gestation) infants with and without brain injury. We recruited 107 VPT infants - including 55 with brain injury (grade III-IV intraventricular hemorrhage, cystic periventricular leukomalacia, post-hemorrhagic hydrocephalus) - and collected FC data at/near term-equivalent age (35-45 weeks postmenstrual age). Correlation coefficients were used to calculate the FC between bilateral motor and visual cortices and thalami. At two years corrected-age, motor outcomes were assessed with the Bayley Scales of Infant and Toddler Development, 3rd edition. Multiple imputation was used to estimate missing data, and regression models related FC measures to motor outcomes. Within the brain-injured group only, interhemispheric motor cortex FC was positively related to gross motor outcomes. Thalamocortical and visual FC were not related to motor scores. This suggests neonatal alterations in motor system FC may provide prognostic information about impairments in children with brain injury.

Inferring The Dynamical Effects Of Stroke Lesions Through Whole-Brain Modeling, Sebastian Idesis, Chiara Favaretto, Nicholas V Metcalf, Joseph C Griffis, Gordon L Shulman, Maurizio Corbetta, Gustavo Deco

2020-Current year OA Pubs

Understanding the effect of focal lesions (stroke) on brain structure-function traditionally relies on behavioral analyses and correlation with neuroimaging data. Here we use structural disconnection maps from individual lesions to derive a causal mechanistic generative whole-brain model able to explain both functional connectivity alterations and behavioral deficits induced by stroke. As compared to other models that use only the local lesion information, the similarity to the empirical fMRI connectivity increases when the widespread structural disconnection information is considered. The presented model classifies behavioral impairment severity with higher accuracy than other types of information (e.g.: functional connectivity). We assessed topological measures …

Cost And Value In Contemporary Heart Failure Clinical Guidance Documents, John W. Ostrominski, Sameer Hirji, Ankeet S. Bhatt, Javed Butler, Mona Fiuzat, Gregg C. Fonarow, Paul A. Heidenreich, James L. Januzzi, Carolyn S. P. Lam, Thomas M. Maddox, Christopher M. O'Connor, Muthiah Vaduganathan

2020-Current year OA Pubs

OBJECTIVES: This study sought to evaluate the frequency and nature of cost/value statements in contemporary heart failure (HF) clinical guidance documents (CGDs).

BACKGROUND: In an era of rising health care costs and expanding therapeutic options, there is an increasing need for formal consideration of cost and value in the development of HF CGDs.

METHODS: HF CGDs published by major professional cardiovascular organizations between January 2010 and February 2021 were reviewed for the inclusion of cost/value statements.

RESULTS: Overall, 33 documents were identified, including 5 (15%) appropriate use criteria, 7 (21%) clinical practice guidelines, and 21 (64%) expert consensus documents. Most …

Creation Of Philadelphia Chromosome By Crispr/Cas9-Mediated Double Cleavages On Bcr And Abl1 Genes As A Model For Initial Event In Leukemogenesis, Minori Tamai, Kenji Kamimoto, Kohei Omachi, Et Al.

2020-Current year OA Pubs

The Philadelphia (Ph) chromosome was the first translocation identified in leukemia. It is supposed to be generated by aberrant ligation between two DNA double-strand breaks (DSBs) at the BCR gene located on chromosome 9q34 and the ABL1 gene located on chromosome 22q11. Thus, mimicking the initiation process of translocation, we induced CRISPR/Cas9-mediated DSBs simultaneously at the breakpoints of the BCR and ABL1 genes in a granulocyte-macrophage colony-stimulating factor (GM-CSF) dependent human leukemia cell line. After transfection of two single guide RNAs (sgRNAs) targeting intron 13 of the BCR gene and intron 1 of the ABL1 gene, a factor-independent subline was …

Estimation Of Intrafamilial Dna Contamination In Family Trio Genome Sequencing Using Deviation From Mendelian Inheritance, Christopher J Yoon, Brian Wiley, Malachi Griffith, Obi L Griffith, Et Al.

2020-Current year OA Pubs

With the increasing number of sequencing projects involving families, quality control tools optimized for family genome sequencing are needed. However, accurately quantifying contamination in a DNA mixture is particularly difficult when genetically related family members are the sources. We developed TrioMix, a maximum likelihood estimation (MLE) framework based on Mendel's law of inheritance, to quantify DNA mixture between family members in genome sequencing data of parent-offspring trios. TrioMix can accurately deconvolute any intrafamilial DNA contamination, including parent-offspring, sibling-sibling, parent-parent, and even multiple familial sources. In addition, TrioMix can be applied to detect genomic abnormalities that deviate from Mendelian inheritance patterns, …

Induction Egfr Tyrosine Kinase Inhibitors Prior To Definitive Chemoradiotherapy In Unresectable Stage Iii Egfr-Mutated Non-Small Cell Lung Cancer, Jacqueline V Aredo, Heather A Wakelee, Angela Bik-Yu Hui, Sukhmani K Padda, Nitin D Joshi, H Henry Guo, Aadel Chaudhuri, Maximilian Diehn, Billy W Loo Jr, Joel W Neal

2020-Current year OA Pubs

INTRODUCTION: Increasing evidence suggests that consolidation durvalumab confers limited benefits for patients with stage III EGFR-mutated NSCLC. Induction or maintenance EGFR tyrosine kinase inhibitors (TKIs) added to concurrent chemoradiotherapy (CRT) may optimize definitive treatment, but there are limited data supporting an induction TKI strategy.

METHODS: We evaluated the efficacy and safety of induction EGFR TKIs administered before concurrent CRT in a retrospective series of patients with unresectable locally advanced EGFR-mutated NSCLC. Circulating tumor DNA (ctDNA) analysis was performed on a patient subset using CAPP-seq and correlated with outcomes.

RESULTS: Of six patients, three received erlotinib and three osimertinib as induction …

Detection Of Emerging Neurodegeneration Using Bayesian Linear Mixed-Effect Modeling, Yann Cobigo, Richard J Perrin, Et Al.

2020-Current year OA Pubs

Early detection of neurodegeneration, and prediction of when neurodegenerative diseases will lead to symptoms, are critical for developing and initiating disease modifying treatments for these disorders. While each neurodegenerative disease has a typical pattern of early changes in the brain, these disorders are heterogeneous, and early manifestations can vary greatly across people. Methods for detecting emerging neurodegeneration in any part of the brain are therefore needed. Prior publications have described the use of Bayesian linear mixed-effects (BLME) modeling for characterizing the trajectory of change across the brain in healthy controls and patients with neurodegenerative disease. Here, we use an extension …

Cgas-Sting Pathway Targeted Therapies And Their Applications In The Treatment Of High-Grade Glioma, Shashwat Tripathi, Hinda Najem, Akanksha Sanjay Mahajan, Peng Zhang, Justin T Low, Alexander H Stegh, Michael A Curran, David M Ashley, Charles David James, Amy B Heimberger

2020-Current year OA Pubs

Median survival of patients with glioblastoma (GBM) treated with standard of care which consists of maximal safe resection of the contrast-enhancing portion of the tumor followed by radiation therapy with concomitant adjuvant temozolomide (TMZ) remains 15 months. The tumor microenvironment (TME) is known to contain immune suppressive myeloid cells with minimal effector T cell infiltration. Stimulator of interferon genes (STING) is an important activator of immune response and results in production of Type 1 interferon and antigen presentation by myeloid cells. This review will discuss important developments in STING agonists, potential biomarkers for STING response, and new combinatorial therapeutic approaches …

Understanding The Contribution Of Metabolism To Mycobacterium Tuberculosis Drug Tolerance, Amanda N Samuels, Erin R Wang, Gregory A Harrison, Joy C Valenta, Christina L Stallings

2020-Current year OA Pubs

Treatment of

A Role For An Htlv-1 Vaccine?, Lee Ratner

2020-Current year OA Pubs

HTLV-1 is a global infection with 5-20 million infected individuals. Although only a minority of infected individuals develop myelopathy, lymphoproliferative malignancy, or inflammatory disorders, infection is associated with immunosuppression and shorter survival. Transmission of HTLV-1 is through contaminated blood or needles, mother-to-child exposure through breast-feeding, and sexual intercourse. HTLV-1 is a delta retrovirus that expresses immunogenic Gag, Envelope, TAX, and Hbz proteins. Neutralizing antibodies have been identified directed against the surface envelope protein, and cytotoxic T-cell epitopes within TAX have been characterized. Thus far, there have been few investigations of vaccines directed against each of these proteins, with limited responses, …

Program Adaptation By Health Departments, Louise Farah Saliba, Peg Allen, Stephanie L Mazzucca, Emily Rodriguez Weno, Sarah Moreland-Russell, Margaret Padek, Ross C Brownson

2020-Current year OA Pubs

INTRODUCTION: The dissemination of evidence-based interventions (i.e., programs, practices, and policies) is a core function of US state health departments (SHDs). However, interventions are originally designed and tested with a specific population and context. Hence, adapting the intervention to meet the real-world circumstances and population's needs can increase the likelihood of achieving the expected health outcomes for the target population from the implemented intervention. This study identified how SHD employees decide to adapt public health programs and what influences decisions on how to adapt them.

MATERIALS AND METHODS: SHD employees (

RESULTS: Data, outcomes, and health department evaluations influenced decisions …

Survival After Simultaneous Pancreas-Kidney Transplantation In Type 1 Diabetes: The Critical Role Of Early Pancreas Allograft Function, Mengmeng Ji, Mei Wang, Wenjun Hu, Mohamed Ibrahim, Krista L. Lentine, Massini Merzkani, Haris Murad, Yazen Al-Hosni, Ronald Parsons, Jason Wellen, Su-Hsin Chang, Tarek Alhamad

2020-Current year OA Pubs

Simultaneous pancreas-kidney transplantation (SPK) carries about a 7%-22% risk of technical failure, but the impact of early pancreas allograft loss on subsequent kidney graft and patient survival is not well-defined. We examined national transplant registry data for type 1 diabetic patients who received SPK between 2000 and 2021. Associations of transplant type (i.e., SPK, deceased-donor kidney transplant [DDKA], living-donor kidney transplant [LDKA]) with kidney graft failure and patient survival were estimated by multivariable inverse probability of treatment-weighted accelerated failure-time models. Compared to SPK recipients with a functioning pancreas graft 3 months posttransplant (SPK,P+), LDKA had 18% (Time Ratio [TR] 0.82, …

In And Out: Leishmania Metastasis By Hijacking Lymphatic System And Migrating Immune Cells, Baijayanti Jha, Marta Reverte, Catherine Ronet, Florence Prevel, Florence D Morgenthaler, Chantal Desponds, Lon-Fye Lye, Katherine L Owens, Leonardo Scarpellino, Lalit Kumar Dubey, Amélie Sabine, Tatiana V Petrova, Sanjiv A Luther, Stephen M Beverley, Nicolas Fasel

2020-Current year OA Pubs

The lymphatic system plays a crucial role in mounting immune response against intracellular pathogens, and recent studies have documented its role in facilitating tumor dissemination linked largely with cancer cells. However, in mucocutaneous leishmaniasis (MCL) caused by

Apoe Mediated Neuroinflammation And Neurodegeneration In Alzheimer's Disease, Samira Parhizkar, David M Holtzman

2020-Current year OA Pubs

Neuroinflammation is a central mechanism involved in neurodegeneration as observed in Alzheimer's disease (AD), the most prevalent form of neurodegenerative disease. Apolipoprotein E4 (APOE4), the strongest genetic risk factor for AD, directly influences disease onset and progression by interacting with the major pathological hallmarks of AD including amyloid-β plaques, neurofibrillary tau tangles, as well as neuroinflammation. Microglia and astrocytes, the two major immune cells in the brain, exist in an immune-vigilant state providing immunological defense as well as housekeeping functions that promote neuronal well-being. It is becoming increasingly evident that under disease conditions, these immune cells become progressively dysfunctional in …

Silver Jubilee: 25 Years Of The First Demonstration Of The Direct Effect Of Phosphate On The Parathyroid Cell, Jordi Bover, Adriana Dusso, Et Al.

2020-Current year OA Pubs

Although phosphorus is an essential element for life, it is not found in nature in its native state but rather combined in the form of inorganic phosphates (PO

Psychiatric Comorbidity And Psychosocial Stressors Among People Initiating Hiv Care In Cameroon, Angela M. Parcesepe, Lindsey M. Filiatreau, Peter Vanes Ebasone, Anastase Dzudie, Brian W. Pence, Milton Wainberg, Marcel Yotebieng, Kathryn Anastos, Eric Pefura-Yone, Denis Nsame, Rogers Ajeh, Denis Nash

2020-Current year OA Pubs

BACKGROUND: Psychiatric comorbidity, the presence of two or more mental health disorders, has been associated with suboptimal HIV treatment outcomes. Little is known about the prevalence of psychiatric comorbidity among people with HIV (PWH) in sub-Saharan Africa.

METHODS: We conducted interviews with PWH initiating HIV care in Cameroon between June 2019 and March 2020. Depression, anxiety, post-traumatic stress disorder (PTSD), and harmful drinking were dichotomized to represent those with and without symptoms of each. Psychiatric comorbidity was defined as having symptoms of two or more disorders assessed. Moderate or severe household hunger, high anticipatory HIV-related stigma, low social support, and …

Modifications To Student Quarantine Policies In K-12 Schools Implementing Multiple Covid-19 Prevention Strategies Restores In-Person Education Without Increasing Sars-Cov-2 Transmission Risk, January-March 2021, Patrick Dawson, Sara Malone, Stephanie A. Fritz, Brock K. Montgomery, Mary Boyle, Brett Maricque, Albert M. Lai, Julie A. Neidich, Rachel C. Orscheln, Jason G Newland, Et Al.

2020-Current year OA Pubs

OBJECTIVE: To determine whether modified K-12 student quarantine policies that allow some students to continue in-person education during their quarantine period increase schoolwide SARS-CoV-2 transmission risk following the increase in cases in winter 2020-2021.

METHODS: We conducted a prospective cohort study of COVID-19 cases and close contacts among students and staff (n = 65,621) in 103 Missouri public schools. Participants were offered free, saliva-based RT-PCR testing. The projected number of school-based transmission events among untested close contacts was extrapolated from the percentage of events detected among tested asymptomatic close contacts and summed with the number of detected events for a …

The First 20 Months Of The Covid-19 Pandemic: Mortality, Intubation And Icu Rates Among 104,590 Patients Hospitalized At 21 United States Health Systems, Michael C. Fiore, Li-Shiun Chen, Et Al.

2020-Current year OA Pubs

MAIN OBJECTIVE: There is limited information on how patient outcomes have changed during the COVID-19 pandemic. This study characterizes changes in mortality, intubation, and ICU admission rates during the first 20 months of the pandemic.

STUDY DESIGN AND METHODS: University of Wisconsin researchers collected and harmonized electronic health record data from 1.1 million COVID-19 patients across 21 United States health systems from February 2020 through September 2021. The analysis comprised data from 104,590 adult hospitalized COVID-19 patients. Inclusion criteria for the analysis were: (1) age 18 years or older; (2) COVID-19 ICD-10 diagnosis during hospitalization and/or a positive COVID-19 PCR …

Fluorescence Imaging Of Beta Cell Primary Cilia, Zipeng A Li, Jung Hoon Cho, Louis G Woodhams, Jing W Hughes

2020-Current year OA Pubs

Primary cilia are slender cell-surface organelles that project into the intercellular space. In pancreatic beta cells, primary cilia coordinate a variety of cell responses including GPCR signaling, calcium influx, and insulin secretion, along with likely many underappreciated roles in islet development and differentiation. To study cilia function in islet biology, direct visualization of primary cilia by microscopic methods is often a necessary first step. Ciliary abundance, distribution, and morphology are heterogeneous among islet cells and are best visualized by fluorescence microscopy, the tools for which are readily accessible to most researchers. Here we present a collection of fluorescence imaging methods …

Magnetic Resonance Imaging Of The Supra-Cervical Fetal Membrane Detects An Increased Risk Of Prelabor Rupture Of Membranes, Wenxu Qi, Peinan Zhao, Wei Wang, Zichao Wen, Zhexian Sun, Wenjie Wu, Pamela Karen Woodard, Qing Wang, Robert C Mckinstry, Yong Wang

2020-Current year OA Pubs

OBJECTIVE: In 10% of term deliveries and 40% of preterm deliveries, the fetal membrane (FM) ruptures before labor. However, the ability to predict these cases of premature rupture of membranes (PROM) and preterm premature rupture of membranes (PPROM) is very limited. In this paper, our objective was to determine whether a prediction method based on T2 weighted magnetic resonance imaging (MRI) of the supra-cervical FM could predict PROM and PPROM.

METHODS: This prospective cohort study enrolled 77 women between the 28th and 37th weeks of gestation. Two indicators of fetal membrane defects, including prolapsed depth >5 mm and signal abnormalities, …

One Vaccine To Counter Many Diseases? Modeling The Economics Of Oral Polio Vaccine Against Child Mortality And Covid-19, Angela Y Chang, Peter Aaby, Michael S Avidan, Christine S Benn, Stefano M Bertozzi, Lawrence Blatt, Konstantin Chumakov, Shabaana A Khader, Shyam Kottilil, Madhav Nekkar, Mihai G Netea, Annie Sparrow, Dean T Jamison

2020-Current year OA Pubs

INTRODUCTION: Recent reviews summarize evidence that some vaccines have heterologous or non-specific effects (NSE), potentially offering protection against multiple pathogens. Numerous economic evaluations examine vaccines' pathogen-specific effects, but less than a handful focus on NSE. This paper addresses that gap by reporting economic evaluations of the NSE of oral polio vaccine (OPV) against under-five mortality and COVID-19.

MATERIALS AND METHODS: We studied two settings: (1) reducing child mortality in a high-mortality setting (Guinea-Bissau) and (2) preventing COVID-19 in India. In the former, the intervention involves three annual campaigns in which children receive OPV incremental to routine immunization. In the latter, …

Expansion Of A Novel Population Of Nk Cells With Low Ribosome Expression In Juvenile Dermatomyositis, Kinsey A Hilliard, Allison A Throm, Jeanette T Pingel, Nermina Saucier, Hani S Zaher, Anthony R French

2020-Current year OA Pubs

Juvenile dermatomyositis (JDM) is a pediatric autoimmune disease associated with characteristic rash and proximal muscle weakness. To gain insight into differential lymphocyte gene expression in JDM, peripheral blood mononuclear cells from 4 new-onset JDM patients and 4 healthy controls were sorted into highly enriched lymphocyte populations for RNAseq analysis. NK cells from JDM patients had substantially greater differentially expressed genes (273) than T (57) and B (33) cells. Upregulated genes were associated with the innate immune response and cell cycle, while downregulated genes were associated with decreased ribosomal RNA. Suppressed ribosomal RNA in JDM NK cells was validated by measuring …

Environmentally-Triggered Contraction Of The Norovirus Virion Determines Diarrheagenic Potential, Emily W Helm, Elizabeth A Kennedy, Megan T Baldridge, Et Al.

2020-Current year OA Pubs

Noroviruses are the leading cause of severe childhood diarrhea and foodborne disease worldwide. While they are a major cause of disease in all age groups, infections in the very young can be quite severe with annual estimates of 50,000-200,000 fatalities in children under 5 years old. In spite of the remarkable disease burden associated with norovirus infections in people, very little is known about the pathogenic mechanisms underlying norovirus diarrhea, principally because of the lack of tractable small animal models. We recently demonstrated that wild-type neonatal mice are susceptible to murine norovirus (MNV)-induced acute self-resolving diarrhea in a time course …

Intraocular Human Cytomegaloviruses Of Ocular Diseases Are Distinct From Those Of Viremia And Are Capable Of Escaping From Innate And Adaptive Immunity By Exploiting Hla-E-Mediated Peripheral And Central Tolerance, Mariko Shirane, Michael Paley, Wayne M Yokoyama, Et Al.

2020-Current year OA Pubs

Human cytomegalovirus (HCMV) infections develop into CMV diseases that result in various forms of manifestations in local organs. CMV-retinitis is a form of CMV disease that develops in immunocompromised hosts with CMV-viremia after viruses in the peripheral circulation have entered the eye. In the HCMV genome, extensive diversification of the UL40 gene has produced peptide sequences that modulate NK cell effector functions when loaded onto HLA-E and are subsequently recognized by the NKG2A and NKG2C receptors. Notably, some HCMV strains carry UL40 genes that encode peptide sequences identical to the signal peptide sequences of specific HLA-A and HLA-C allotypes, which …

Automatic Wide Complex Tachycardia Differentiation Using Mathematically Synthesized Vectorcardiogram Signals, Anthony H Kashou, Sarah Lococo, Trevon D Mcgill, Christopher M Evenson, Abhishek J Deshmukh, David O Hodge, Daniel H Cooper, Sandeep S Sodhi, Phillip S Cuculich, Samuel J Asirvatham, Peter A Noseworthy, Christopher V Desimone, Adam M May

2020-Current year OA Pubs

BACKGROUND: Automated wide complex tachycardia (WCT) differentiation into ventricular tachycardia (VT) and supraventricular wide complex tachycardia (SWCT) may be accomplished using novel calculations that quantify the extent of mean electrical vector changes between the WCT and baseline electrocardiogram (ECG). At present, it is unknown whether quantifying mean electrical vector changes within three orthogonal vectorcardiogram (VCG) leads (X, Y, and Z leads) can improve automated VT and SWCT classification.

METHODS: A derivation cohort of paired WCT and baseline ECGs was used to derive five logistic regression models: (i) one novel WCT differentiation model (i.e., VCG Model), (ii) three previously developed WCT …

Co-Clinical Fdg-Pet Radiomic Signature In Predicting Response To Neoadjuvant Chemotherapy In Triple-Negative Breast Cancer, Sudipta Roy, Timothy D Whitehead, Shunqiang Li, Foluso O Ademuyiwa, Richard L Wahl, Farrokh Dehdashti, Kooresh I Shoghi

2020-Current year OA Pubs

PURPOSE: We sought to exploit the heterogeneity afforded by patient-derived tumor xenografts (PDX) to first, optimize and identify robust radiomic features to predict response to therapy in subtype-matched triple negative breast cancer (TNBC) PDX, and second, to implement PDX-optimized image features in a TNBC co-clinical study to predict response to therapy using machine learning (ML) algorithms.

METHODS: TNBC patients and subtype-matched PDX were recruited into a co-clinical FDG-PET imaging trial to predict response to therapy. One hundred thirty-one imaging features were extracted from PDX and human-segmented tumors. Robust image features were identified based on reproducibility, cross-correlation, and volume independence. A …

Exploring How Public Health Partnerships With Community-Based Organizations (Cbos) Can Be Leveraged For Health Promotion And Community Health., Senila Yasmin, Rayna Haque, Kaneza Kadambaya, Marzia Maliha, Maha Sheikh

Student Papers, Posters & Projects

The Academic Public Health Corps (APHC) works to support local public health in Massachusetts through varying models of collaboration. In the setting of the COVID-19 pandemic, one initiative of the APHC has been to partner with community-based organizations (CBOs) to address vaccine hesitancy and improve overall community health. The purpose of this article is to share how the APHC partnered with CBOs in Massachusetts to address COVID-19 concerns within their respective communities, and present strategies to empower communities, share resources, and increase health promotion. The APHC partnered with 2 CBOs who received the Massachusetts COVID-19 Community Grants distributed by Health …

Identification Of Serum Mirna Signature And Establishment Of A Nomogram For Risk Stratification In Patients With Pancreatic Ductal Adenocarcinoma, Raju Kandimalla, Tadanobu Shimura, Saurav Mallik, Fuminori Sonohara, Susan Tsai, Douglas B Evans, Song Cheol Kim, Hideo Baba, Yasuhiro Kodera, Daniel Von Hoff, Xi Chen, Ajay Goel

Faculty, Staff and Students Publications

OBJECTIVE: The aim of the study was to perform mRNA-miRNA regulatory network analyses to identify a miRNA panel for molecular subtype identification and stratification of high-risk patients with pancreatic ductal adenocarcinoma (PDAC).

BACKGROUND: Recent transcriptional profiling effort in PDAC has led to the identification of molecular subtypes that associate with poor survival; however, their clinical significance for risk stratification in patients with PDAC has been challenging.

METHODS: By performing a systematic analysis in The Cancer Genome Atlas and International Cancer Genome Consortium cohorts, we discovered a panel of miRNAs that associated with squamous and other poor molecular subtypes in PDAC. …

Targeting The Pro-Survival Protein Bcl-2 To Prevent Breast Cancer, Adelaide Young, Wen Bu, Weiyu Jiang, Amy Ku, Jyoti Kapali, Sagar Dhamne, Lan Qin, Susan G Hilsenbeck, Yi-Chieh Nancy Du, Yi Li

Faculty, Staff and Students Publications

Current chemopreventive strategies require 3-5 years of continuous treatment and have the concerns of significant side effects; therefore, new chemopreventive agents that require shorter and safer treatments are urgently needed. In this study, we developed a new murine model of breast cancer that mimics human breast cancer initiation and is ideal for testing the efficacy of chemopreventive therapeutics. In this model, introduction of lentivirus carrying a PIK3CA gene mutant commonly found in breast cancers infects a small number of the mammary cells, leading to atypia first and then to ductal carcinomas that are positive for both estrogen receptor and progesterone …