Digital Commons Network^™

Polyploid Giant Cancer Cells And Ovarian Cancer: New Insights Into Mitotic Regulators And Polyploidy†, Joanne S Richards, Nicholes R Candelaria, Rainer B Lanz

Faculty, Staff and Students Publications

Current first-line treatment of patients with high-grade serous ovarian cancer (HGSOC) involves the use of cytotoxic drugs that frequently lead to recurrent tumors exhibiting increased resistance to the drugs and poor patient survival. Strong evidence is accumulating to show that HGSOC tumors and cell lines contain a subset of cells called polyploidy giant cancer cells (PGCCs) that act as stem-like, self-renewing cells. These PGCCs appear to play a key role in tumor progression by generating drug-resistant progeny produced, in part, as a consequence of utilizing a modified form of mitosis known as endoreplication. Thus, developing drugs to target PGCCs and …

Cryptic Constituents: The Paradox Of High Flux–Low Concentration Components Of Aquatic Ecosystems, Malin Olofsson, Mary E. Power, David A. Stahl, Yvonne Vadeboncoeur, Michael T. Brett

Biological Sciences Faculty Publications

The interface between terrestrial ecosystems and inland waters is an important link in the global carbon cycle. However, the extent to which allochthonous organic matter entering freshwater systems plays a major role in microbial and higher-trophic-level processes is under debate. Human perturbations can alter fluxes of terrestrial carbon to aquatic environments in complex ways. The biomass and production of aquatic microbes are traditionally thought to be resource limited via stoichiometric constraints such as nutrient ratios or the carbon standing stock at a given timepoint. Low concentrations of a particular constituent, however, can be strong evidence of its importance in food …

Das181 Treatment Of Severe Lower Respiratory Tract Parainfluenza Virus Infection In Immunocompromised Patients: A Phase 2 Randomized, Placebo-Controlled Study, Roy F Chemaly, Francisco M Marty, Cameron R Wolfe, Steven J Lawrence, Sanjeet Dadwal, Rosemary Soave, Jason Farthing, Stephen Hawley, Paul Montanez, Jimmy Hwang, Jennifer Hui-Chun Ho, Stanley Lewis, George Wang, Michael Boeckh

2020-Current year OA Pubs

BACKGROUND: There are no antiviral therapies for parainfluenza virus (PIV) infections. DAS181, a sialidase fusion protein, has demonstrated activity in in vitro and in animal models of PIV.

METHODS: Adult immunocompromised patients diagnosed with PIV lower respiratory tract infection (LRTI) who required oxygen supplementation were randomized 2:1 to nebulized DAS181 (4.5 mg/day) or matching placebo for up to 10 days. Randomization was stratified by need for mechanical ventilation (MV) or supplemental oxygen (SO). The primary endpoint was the proportion of patients reaching clinical stability survival (CSS) defined as returning to room air (RTRA), normalization of vital signs for at least …

The Age Presents Introduction To Geroscience Video Lecture Series., Alessandro Bitto, Mitchell B Lee, Cristal M Hill, Ron Korstanje, Matt Kaeberlein

Faculty Research 2021

The AGE Presents Introduction to Geroscience video lecture series is a collection of high-quality didactic video lectures and associated teaching materials focused on foundational topics in aging biology. The videos are made freely available on YouTube and are targeted toward an audience familiar with concepts learned in the first year of a college undergraduate biology/biomedical major. Members of the American Aging Association also receive the original lecture slides and lecture notes, with additional course materials to be developed in the future. We expect that these lectures will enhance understanding of geroscience among the general public while also providing tools that …

Mitophagy Protein Pink1 Suppresses Colon Tumor Growth By Metabolic Reprogramming Via P53 Activation And Reducing Acetyl-Coa Production, Kunlun Yin, Jordan Lee, Zhaoli Liu, Hyeoncheol Kim, David R Martin, Dandan Wu, Meilian Liu, Xiang Xue

Pathology Research and Scholarship

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in the US. Understanding the mechanisms of CRC progression is essential to improve treatment. Mitochondria is the powerhouse for healthy cells. However, in tumor cells, less energy is produced by the mitochondria and metabolic reprogramming is an early hallmark of cancer. The metabolic differences between normal and cancer cells are being interrogated to uncover new therapeutic approaches. Mitochondria targeting PTEN-induced kinase 1 (PINK1) is a key regulator of mitophagy, the selective elimination of damaged mitochondria by autophagy. Defective mitophagy is increasingly associated with various diseases including CRC. However, a …

Cd44 Engagement Enhances Acute Myeloid Leukemia Cell Adhesion To The Bone Marrow Microenvironment By Increasing Vla-4 Avidity, Julia C. Gutjahr, Elisabeth Bayer, Xiaobing Yu, Julia M. Laufer, Jan P. Höpner, Suzana Tesanovic, Andrea Härzschel, Georg Auer, Tanja Rieß, Astrid Salmhofer, Eva Szenes, Theresa Haslauer, Valerie Durand-Onayli, Andrea Ramspacher, Sandra P. Pennisi, Marc Artinger, Nadja Zaborsky, Alexandre Chigaev, Fritz Aberger, Daniel Neureiter, Lisa Pleyer, Daniel F. Legler, Veronique Orian-Rousseau, Richard Greil, Tanja N. Hartmann

Pathology Research and Scholarship

Adhesive properties of leukemia cells shape the degree of organ infiltration and the extent of leukocytosis. CD44 and the integrin VLA-4, a CD49d/CD29 heterodimer, are important factors of progenitor cell adhesion in bone marrow (BM). Here, we report their cooperation in acute myeloid leukemia (AML) by a novel non-classical CD44-mediated way of inside-out VLA-4 activation. In primary AML BM samples from patients and the OCI-AML3 cell line, CD44 engagement by hyaluronan induced inside-out activation of VLA-4 resulting in enhanced leukemia cell adhesion on VCAM-1. This was independent from VLA-4 affinity regulation but based on ligand-induced integrin clustering on the cell …

In Situ Chromatin Interaction Analysis Using Paired-End Tag Sequencing., Ping Wang, Yuliang Feng, Kun Zhu, Haoxi Chai, Ya-Ting Chang, Xiaofei Yang, Xiyuan Liu, Chen Shen, Eva Gega, Byoungkoo Lee, Minji Kim, Xiaoan Ruan, Yijun Ruan

Faculty Research 2021

Chromatin Interaction Analysis Using Paired-End Tag Sequencing (ChIA-PET) is an established method to map protein-mediated chromatin interactions. A limitation, however, is that it requires a hundred million cells per experiment, which hampers its broad application in biomedical research, particularly in studies in which it is impractical to obtain a large number of cells from rare samples. To reduce the required input cell number while retaining high data quality, we developed an in situ ChIA-PET protocol, which requires as few as 1 million cells. Here, we describe detailed step-by-step procedures for performing in situ ChIA-PET from cultured cells, including both an …

Tumor-On-Chip Modeling Of Organ-Specific Cancer And Metastasis, Nuala Del Piccolo, Venktesh S Shirure, Ye Bi, S Peter Goedegebuure, Sepideh Gholami, Christopher C W Hughes, Ryan C Fields, Steven C George

2020-Current year OA Pubs

Every year, cancer claims millions of lives around the globe. Unfortunately, model systems that accurately mimic human oncology - a requirement for the development of more effective therapies for these patients - remain elusive. Tumor development is an organ-specific process that involves modification of existing tissue features, recruitment of other cell types, and eventual metastasis to distant organs. Recently, tissue engineered microfluidic devices have emerged as a powerful in vitro tool to model human physiology and pathology with organ-specificity. These organ-on-chip platforms consist of cells cultured in 3D hydrogels and offer precise control over geometry, biological components, and physiochemical properties. …

Acute Myeloid Leukemia: Therapy Resistance And A Potential Role For Tetraspanin Membrane Scaffolds, Muskan Floren, Jennifer M. Gillette

Pathology Research and Scholarship

Acute myeloid leukemia (AML) is characterized by the disruption of myeloid differentiation and accumulation of blast cells in the bone marrow. While AML patients respond favorably to induction chemotherapy, long-term outcomes remain poor due to a high rate of chemoresistance. Advances with targeted therapies, which can be used in combination with conventional chemotherapy, have expanded therapeutic options for patients. However, remission is often short-lived and followed by disease relapse and drug resistance. Therefore, there is a substantial need to improve treatment options by identifying novel molecular and cellular targets that regulate AML chemosensitivity. Membrane scaffolds such as the tetraspanin family …

The Association Between Outdoor Artificial Light At Night And Breast Cancer Risk In Black And White Women In The Southern Community Cohort Study, Qian Xiao, Gretchen L Gierach, Cici Bauer, William J Blot, Peter James, Rena R Jones

Faculty, Staff and Student Publications

No abstract provided.

Genome-Wide Association Study Of Serum Metabolites In The African American Study Of Kidney Disease And Hypertension, Shengyuan Luo, Elena V Feofanova, Adrienne Tin, Sarah Tung, Eugene P Rhee, Josef Coresh, Dan E Arking, Aditya Surapaneni, Pascal Schlosser, Yong Li, Anna Köttgen, Bing Yu, Morgan E Grams

Faculty, Staff and Student Publications

The genome-wide association study (GWAS) is a powerful means to study genetic determinants of disease traits and generate insights into disease pathophysiology. to date, few GWAS of circulating metabolite levels have been performed in African Americans with chronic kidney disease. Hypothesizing that novel genetic-metabolite associations may be identified in a unique population of African Americans with a lower glomerular filtration rate (GFR), we conducted a GWAS of 652 serum metabolites in 619 participants (mean measured glomerular filtration rate 45 mL/min/1.73m

Non-Motor Phenotypic Subgroups In Adult-Onset Idiopathic, Isolated, Focal Cervical Dystonia, Megan E Wadon, Joel S Perlmutter, Et Al

Open Access Publications

BACKGROUND: Non-motor symptoms are well established phenotypic components of adult-onset idiopathic, isolated, focal cervical dystonia (AOIFCD). However, improved understanding of their clinical heterogeneity is needed to better target therapeutic intervention. Here, we examine non-motor phenotypic features to identify possible AOIFCD subgroups.

METHODS: Participants diagnosed with AOIFCD were recruited via specialist neurology clinics (dystonia wales: n = 114, dystonia coalition: n = 183). Non-motor assessment included psychiatric symptoms, pain, sleep disturbance, and quality of life, assessed using self-completed questionnaires or face-to-face assessment. Both cohorts were analyzed independently using Cluster, and Bayesian multiple mixed model phenotype analyses to investigate the relationship between …

Race And Ethnicity Representation In Clinical Trials: Findings From A Literature Review Of Phase I Oncology Trials, D Ross Camidge, Haeseong Park, Karen E Smoyer, Ira Jacobs, Lauren J Lee, Zemfira Askerova, Justin Mcginnis, Yousef Zakharia

2020-Current year OA Pubs

No abstract provided.

Phase Ii Study Of Durvalumab Plus Tremelimumab As Therapy For Patients With Previously Treated Anti-Pd-1/Pd-L1 Resistant Stage Iv Squamous Cell Lung Cancer (Lung-Map Substudy S1400f, Nct03373760), Natasha B Leighl, Jeffrey D Bradley, Et Al

2020-Current year OA Pubs

INTRODUCTION: S1400F is a non-match substudy of Lung Cancer Master Protocol (Lung-MAP) evaluating the immunotherapy combination of durvalumab and tremelimumab to overcome resistance to anti-programmed death ligand 1 (PD-(L)1) therapy in patients with advanced squamous lung carcinoma (sq non-small-cell lung cancer (NSCLC)).

METHODS: Patients with previously treated sqNSCLC with disease progression after anti-PD-(L)1 monotherapy, who did not qualify for any active molecularly targeted Lung-MAP substudies, were eligible. Patients received tremelimumab 75 mg plus durvalumab 1500 mg once every 28 days for four cycles then durvalumab alone every 28 days until disease progression. The primary endpoint was the objective response rate …

Thioredoxin Reductase Is A Major Regulator Of Metabolism In Leukemia Cells, Sheelarani Karunanithi, Ruifu Liu, Yongchun Hou, Giancarlo Gonzalez, Natasha Oldford, Anne Jessica Roe, Nethrie Idipilly, Kalpana Gupta, Chandra Sekhar Amara, Satwikreddy Putluri, Grace Kyueun Lee, Juan Valentin-Goyco, Lindsay Stetson, Stephen A Moreton, Vasanta Putluri, Shyam M Kavuri, Yogen Saunthararajah, Marcos De Lima, Gregory P Tochtrop, Nagireddy Putluri, David N Wald

Faculty, Staff and Students Publications

Despite the fact that AML is the most common acute leukemia in adults, patient outcomes are poor necessitating the development of novel therapies. We identified that inhibition of Thioredoxin Reductase (TrxR) is a promising strategy for AML and report a highly potent and specific inhibitor of TrxR, S-250. Both pharmacologic and genetic inhibition of TrxR impairs the growth of human AML in mouse models. We found that TrxR inhibition leads to a rapid and marked impairment of metabolism in leukemic cells subsequently leading to cell death. TrxR was found to be a major and direct regulator of metabolism in AML …

Neurovascular Regulation In Diabetic Retinopathy And Emerging Therapies, Liyang Ji, Hong Tian, Keith A Webster, Wei Li

Faculty, Staff and Students Publications

Diabetic retinopathy (DR) is the leading cause of vision loss in working adults in developed countries. The disease traditionally classified as a microvascular complication of diabetes is now widely recognized as a neurovascular disorder resulting from disruption of the retinal neurovascular unit (NVU). The NVU comprising retinal neurons, glia and vascular cells coordinately regulates blood flow, vascular density and permeability to maintain homeostasis. Disturbance of the NVU during DR can lead to vision-threatening clinical manifestations. A limited number of signaling pathways have been identified for intercellular communication within the NVU, including vascular endothelial growth factor (VEGF), the master switch for …

Cd148 Deficiency In Fibroblasts Promotes The Development Of Pulmonary Fibrosis, Konstantin Tsoyi, Xiaoliang Liang, Giulia De Rossi, Stefan W Ryter, Kevin Xiong, Sarah G Chu, Xiaoli Liu, Bonna Ith, Lindsay J Celada, Freddy Romero, Matthew J Robertson, Anthony J Esposito, Sergio Poli, Souheil El-Chemaly, Mark A Perrella, Yuanyuan Shi, James Whiteford, Ivan O Rosas

Faculty, Staff and Students Publications

Rationale: CD148/PTRJ (receptor-like protein tyrosine phosphatase η) exerts antifibrotic effects in experimental pulmonary fibrosis via interactions with its ligand syndecan-2; however, the role of CD148 in human pulmonary fibrosis remains incompletely characterized.

Objectives: We investigated the role of CD148 in the profibrotic phenotype of fibroblasts in idiopathic pulmonary fibrosis (IPF).

Methods: Conditional CD148 fibroblast-specific knockout mice were generated and exposed to bleomycin and then assessed for pulmonary fibrosis. Lung fibroblasts (mouse lung and human IPF lung), and precision-cut lung slices from human patients with IPF were isolated and subjected to experimental treatments. A CD148-activating 18-aa mimetic peptide (SDC2-pep) derived from …

The Immunoregulatory Landscape Of Human Tuberculosis Granulomas, Evan Li, Antony Rodriguez, Amber U Luong, David Allen, John Morgan Knight, Farrah Kheradmand, David B Corry

Faculty, Staff and Student Publications

The allergic airway diseases chronic rhinosinusitis (CRS), allergic fungal rhinosinusitis (AFRS), asthma, allergic bronchopulmonary mycosis/aspergillosis (ABPM/A), and cystic fibrosis (CF) share a common immunological signature marked by T H 2 and TH 17 cell predominant immune responses, the production of IgE antibody, and atypical inflammatory cell infiltrate that includes eosinophils and other innate immune effector cells. Severe forms of these disorders have long been recognized as being related to hypersensitivity reactions to environmental fungi. Increasingly however,environmental fungi are assuming a more primary role in the etiology of these disorders, with airway mycosis, a type of non-invasive airway fungal infection,recognized as …

Deep Learning-Based Mixed-Dimensional Gaussian Mixture Model For Characterizing Variability In Cryo-Em, Muyuan Chen, Steven J Ludtke

Faculty, Staff and Students Publications

Structural flexibility and/or dynamic interactions with other molecules is a critical aspect of protein function. Cryogenic electron microscopy (cryo-EM) provides direct visualization of individual macromolecules sampling different conformational and compositional states. While numerous methods are available for computational classification of discrete states, characterization of continuous conformational changes or large numbers of discrete state without human supervision remains challenging. Here we present e2gmm, a machine learning algorithm to determine a conformational landscape for proteins or complexes using a three-dimensional Gaussian mixture model mapped onto two-dimensional particle images in known orientations. Using a deep neural network architecture, e2gmm can automatically resolve the …

Sugar-Sweetened Beverage Consumption May Modify Associations Between Genetic Variants In The Chrebp (Carbohydrate Responsive Element Binding Protein) Locus And Hdl-C (High-Density Lipoprotein Cholesterol) And Triglyceride Concentrations, Danielle E Haslam, Gina M Peloso, Melanie Guirette, Fumiaki Imamura, Traci M Bartz, Achilleas N Pitsillides, Carol A Wang, Ruifang Li-Gao, Jason M Westra, Niina Pitkänen, Kristin L Young, Mariaelisa Graff, Alexis C Wood, Kim V E Braun, Jian'an Luan, Mika Kähönen, Jessica C Kiefte-De Jong, Mohsen Ghanbari, Nathan Tintle, Rozenn N Lemaitre, Dennis O Mook-Kanamori, Kari North, Mika Helminen, Yasmin Mossavar-Rahmani, Linda Snetselaar, Lisa W Martin, Jorma S Viikari, Wendy H Oddy, Craig E Pennell, Frits R Rosendall, M Arfan Ikram, Andre G Uitterlinden, Bruce M Psaty, Dariush Mozaffarian, Jerome I Rotter, Kent D Taylor, Terho Lehtimäki, Olli T Raitakari, Kara A Livingston, Trudy Voortman, Nita G Forouhi, Nick J Wareham, Renée De Mutsert, Steven S Rich, Joann E Manson, Samia Mora, Paul M Ridker, Jordi Merino, James B Meigs, Hassan S Dashti, Daniel I Chasman, Alice H Lichtenstein, Caren E Smith, Josée Dupuis, Mark A Herman, Nicola M Mckeown

Faculty, Staff and Students Publications

BACKGROUND: ChREBP (carbohydrate responsive element binding protein) is a transcription factor that responds to sugar consumption. Sugar-sweetened beverage (SSB) consumption and genetic variants in the

METHODS: Data from 11 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (N=63 599) and the UK Biobank (N=59 220) were used to quantify associations of SSB consumption, genetic variants, and their interaction on HDL-C and triglyceride concentrations using linear regression models. A total of 1606 single nucleotide polymorphisms within or near

RESULTS: In a meta-analysis, rs71556729 was significantly associated with higher HDL-C concentrations only among the highest SSB consumers …

Metabolomics Profiling Of Patients With A-Β+ Ketosis-Prone Diabetes During Diabetic Ketoacidosis, Farook Jahoor, Jean W Hsu, Paras B Mehta, Kelly R Keene, Ruchi Gaba, Surya Narayan Mulukutla, Eunice Caducoy, W Frank Peacock, Sanjeet G Patel, Rasmus Bennet, Ake Lernmark, Ashok Balasubramanyam

Faculty, Staff and Students Publications

When stable and near-normoglycemic, patients with “A−β+” ketosis-prone diabetes (KPD) manifest accelerated leucine catabolism and blunted ketone oxidation, which may underlie their proclivity to develop diabetic ketoacidosis (DKA). To understand metabolic derangements in A−β+ KPD patients during DKA, we compared serum metabolomics profiles of adults during acute hyperglycemic crises, without (n = 21) or with (n = 74) DKA, and healthy control subjects (n = 17). Based on 65 kDa GAD islet autoantibody status, C-peptide, and clinical features, 53 DKA patients were categorized as having KPD and 21 type 1 diabetes (T1D); 21 nonketotic patients were categorized as …

De-Identification Procedures For Magnetic Resonance Images And The Impact On Structural Brain Measures At Different Ages, Elizabeth E L Buimer, Hugo G Schnack, Yaron Caspi, Neeltje E M Van Haren, Mikhail Milchenko, Pascal Pas, Alzheimer's Disease Neuroimaging Initiative, Hilleke E Hulshoff Pol, Rachel M Brouwer

2020-Current year OA Pubs

Surface rendering of MRI brain scans may lead to identification of the participant through facial characteristics. In this study, we evaluate three methods that overwrite voxels containing privacy-sensitive information: Face Masking, FreeSurfer defacing, and FSL defacing. We included structural T1-weighted MRI scans of children, young adults and older adults. For the young adults, test-retest data were included with a 1-week interval. The effects of the de-identification methods were quantified using different statistics to capture random variation and systematic noise in measures obtained through the FreeSurfer processing pipeline. Face Masking and FSL defacing impacted brain voxels in some scans especially in …

Altered Neuronal Physiology, Development, And Function Associated With A Common Chromosome 15 Duplication Involving Chrna7, Kesavan Meganathan, Ramachandran Prakasam, Dustin Baldridge, Paul Gontarz, Bo Zhang, Fumihiko Urano, Azad Bonni, Susan E Maloney, Tychele N Turner, James E Huettner, John N Constantino, Kristen L Kroll

2020-Current year OA Pubs

BACKGROUND: Copy number variants (CNVs) linked to genes involved in nervous system development or function are often associated with neuropsychiatric disease. While CNVs involving deletions generally cause severe and highly penetrant patient phenotypes, CNVs leading to duplications tend instead to exhibit widely variable and less penetrant phenotypic expressivity among affected individuals. CNVs located on chromosome 15q13.3 affecting the alpha-7 nicotinic acetylcholine receptor subunit (CHRNA7) gene contribute to multiple neuropsychiatric disorders with highly variable penetrance. However, the basis of such differential penetrance remains uncharacterized. Here, we generated induced pluripotent stem cell (iPSC) models from first-degree relatives with a 15q13.3 duplication and …

Impact Of Amerind Ancestry And Fads Genetic Variation On Omega-3 Deficiency And Cardiometabolic Traits In Hispanic Populations, Chaojie Yang, Brian Hallmark, Jin Choul Chai, Timothy D O'Connor, Lindsay M Reynolds, Alexis C Wood, Michael Seeds, Yii-Der Ida Chen, Lyn M Steffen, Michael Y Tsai, Robert C Kaplan, Martha L Daviglus, Lawrence J Mandarino, Amanda M Fretts, Rozenn N Lemaitre, Dawn K Coletta, Sarah A Blomquist, Laurel M Johnstone, Chandra Tontsch, Qibin Qi, Ingo Ruczinski, Stephen S Rich, Rasika A Mathias, Floyd H Chilton, Ani Manichaikul

Children’s Nutrition Research Center Staff Publications

Long chain polyunsaturated fatty acids (LC-PUFAs) have critical signaling roles that regulate dyslipidemia and inflammation. Genetic variation in the FADS gene cluster accounts for a large portion of interindividual differences in circulating and tissue levels of LC-PUFAs, with the genotypes most strongly predictive of low LC-PUFA levels at strikingly higher frequencies in Amerind ancestry populations. In this study, we examined relationships between genetic ancestry and FADS variation in 1102 Hispanic American participants from the Multi-Ethnic Study of Atherosclerosis. We demonstrate strong negative associations between Amerind genetic ancestry and LC-PUFA levels. The FADS rs174537 single nucleotide polymorphism (SNP) accounted for much …

Integrated Single-Cell Atlas Of Endothelial Cells Of The Human Lung, Jonas C Schupp, Taylor S Adams, Carlos Cosme, Micha Sam Brickman Raredon, Yifan Yuan, Norihito Omote, Sergio Poli, Maurizio Chioccioli, Kadi-Ann Rose, Edward P Manning, Maor Sauler, Giuseppe Deiuliis, Farida Ahangari, Nir Neumark, Arun C Habermann, Austin J Gutierrez, Linh T Bui, Robert Lafyatis, Richard W Pierce, Kerstin B Meyer, Martijn C Nawijn, Sarah A Teichmann, Nicholas E Banovich, Jonathan A Kropski, Laura E Niklason, Dana Pe'er, Xiting Yan, Robert J Homer, Ivan O Rosas, Naftali Kaminski

Faculty, Staff and Student Publications

BACKGROUND: Cellular diversity of the lung endothelium has not been systematically characterized in humans. We provide a reference atlas of human lung endothelial cells (ECs) to facilitate a better understanding of the phenotypic diversity and composition of cells comprising the lung endothelium.

METHODS: We reprocessed human control single-cell RNA sequencing (scRNAseq) data from 6 datasets. EC populations were characterized through iterative clustering with subsequent differential expression analysis. Marker genes were validated by fluorescent microscopy and in situ hybridization. scRNAseq of primary lung ECs cultured in vitro was performed. The signaling network between different lung cell types was studied. For cross-species …

Potential Benefits Of Bovine Colostrum In Pediatric Nutrition And Health, Per Torp Sangild, Caitlin Vonderohe, Valeria Melendez Hebib, Douglas G Burrin

Children’s Nutrition Research Center Staff Publications

Bovine colostrum (BC), the first milk produced from cows after parturition, is increasingly used as a nutritional supplement to promote gut function and health in other species, including humans. The high levels of whey and casein proteins, immunoglobulins (Igs), and other milk bioactives in BC are adapted to meet the needs of newborn calves. However, BC supplementation may improve health outcomes across other species, especially when immune and gut functions are immature in early life. We provide a review of BC composition and its effects in infants and children in health and selected diseases (diarrhea, infection, growth-failure, preterm birth, necrotizing …

Artificial Intelligence For Classification Of Temporal Lobe Epilepsy With Roi-Level Mri Data: A Worldwide Enigma-Epilepsy Study, Ezequiel Gleichgerrcht, Brent C. Munsell, Saud Alhusaini, Marina K. M. Alvim, Núria Bargalló, Benjamin Bender, Andrea Bernasconi, Neda Bernasconi, Boris Bernhardt, Karen Blackmon, Maria E. Caligiuri, Fernando Cendes, Luis Concha, Patricia M. Desmond, Orrin Devinsky, Colin P. Doherty, Martin Domin, John S. Duncan, Niels K. Focke, Antonio Gambardella, Bo Gong, Renzo Guerrini, Sean N. Hatton, Reetta Kälviäinen, Simon S. Keller, Peter Kochunov, Raviteja Kotikalapudi, Barbara A. K. Kreilkamp, Angelo Labate, Soenke Langner, Sara Larivière, Matteo Lenge, Elaine Lui, Pascal Martin, Mario Mascalchi, Stefano Meletti, Terence J. O'Brien, Heath R. Pardoe, Jose C. Pariente, Jun Xian Rao, Mark P. Richardson, Raúl Rodríguez-Cruces, Theodor Rüber, Ben Sinclair, Hamid Soltanian-Zadeh, Dan J. Stein, Pasquale Striano, Peter N. Taylor, Rhys H. Thomas, Anna Elisabetta Vaudano, Lucy Vivash, Felix Von Podewills, Sjoerd B. Vos, Bernd Weber, Yi Yao, Clarissa Lin Yasuda, Junsong Zhang, Paul M. Thompson, Sanjay M. Sisodiya, Carrie R. Mcdonald, Leonardo Bonilha

Diagnostic Radiology Articles

Artificial intelligence has recently gained popularity across different medical fields to aid in the detection of diseases based on pathology samples or medical imaging findings. Brain magnetic resonance imaging (MRI) is a key assessment tool for patients with temporal lobe epilepsy (TLE). The role of machine learning and artificial intelligence to increase detection of brain abnormalities in TLE remains inconclusive. We used support vector machine (SV) and deep learning (DL) models based on region of interest (ROI-based) structural (n = 336) and diffusion (n = 863) brain MRI data from patients with TLE with ("lesional") and without ("non-lesional") radiographic features …

Myeloid Cell Mediated Immune Suppression In Pancreatic Cancer, Samantha B. Kemp, Marina Pasca Di Magliano, Howard C. Crawford

Research Administration Articles

Pancreatic ductal adenocarcinoma (PDA), the most common pancreatic cancer, is a nearly-universally lethal malignancy. PDA is characterized by extensive infiltration of immunosuppressive myeloid cells, including tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs). Myeloid cells in the tumor microenvironment (TME) inhibit cytotoxic T cell responses promoting carcinogenesis. Immune checkpoint therapy has not been effective in PDA, most likely due to this robust immune suppression, making it critical to elucidate mechanisms behind this phenomenon. Here, we review myeloid cell infiltration and cellular crosstalk in PDA progression and highlight current therapeutic approaches to target myeloid cell-driven immune suppression.

Perception Versus Reality: A National Cohort Analysis Of The Surgery-First Approach For Resectable Pancreatic Cancer, John R. Bergquist, Cornelius A. Thiels, Christopher R. Shubert, Tommy Ivanics, Elizabeth B. Habermann, Santhi S. Vege, Travis E. Grotz, Sean P. Cleary, Rory L. Smoot, Michael L. Kendrick, David M. Nagorney, Mark J. Truty

Surgery Articles

INTRODUCTION: Although surgical resection is necessary, it is not sufficient for long-term survival in pancreatic ductal adenocarcinoma (PDAC). We sought to evaluate survival after up-front surgery (UFS) in anatomically resectable PDAC in the context of three critical factors: (A) margin status; (B) CA19-9; and (C) receipt of adjuvant chemotherapy.

METHODS: The National Cancer Data Base (2010-2015) was reviewed for clinically resectable (stage 0/I/II) PDAC patients. Surgical margins, pre-operative CA19-9, and receipt of adjuvant chemotherapy were evaluated. Patient overall survival was stratified based on these factors and their respective combinations. Outcomes after UFS were compared to equivalently staged patients after neoadjuvant …

The Informed Road Map To Prevention Of Alzheimer Disease: A Call To Arms, Eric Mcdade, Jorge J Llibre-Guerra, David M Holtzman, John C Morris, Randall J Bateman

2020-Current year OA Pubs

Alzheimer disease (AD) prevention trials hold the promise to delay or prevent cognitive decline and dementia onset by intervening before significant neuronal damage occurs. In recent years, the first AD prevention trials have launched and are yielding important findings on the biology of targeting asymptomatic AD pathology. However, there are limitations that impact the design of these prevention trials, including the translation of animal models that recapitulate key stages and multiple pathological aspects of the human disease, missing target validation in asymptomatic disease, uncertain causality of the association of pathophysiologic changes with cognitive and clinical symptoms, and limited biomarker validation …