Digital Commons Network^™

Using Polygenic Scores For Identifying Individuals At Increased Risk Of Substance Use Disorders In Clinical And Population Samples, Peter B. Barr, Emma C. Johnson, Andrey Anokhin, Arpana Agrawal, Et Al.

Open Access Publications

No abstract provided.

The Chromatin Remodeling Enzyme Chd4 Regulates Genome Architecture In The Mouse Brain, Jared V. Goodman, Tomoko Yamada, Yue Yang, Lingchun Kong, Dennis Y. Wu, Guoyan Zhao, Harrison W. Gabel, Azad Bonni

Open Access Publications

No abstract provided.

Comparison Of Differential Accessibility Analysis Strategies For Atac-Seq Data, Paul Gontarz, Shuhua Fu, Xiaoyun Xing, Shaopeng Liu, Benpeng Miao, Viktoriia Bazylianska, Akhil Sharma, Pamela Madden, Kitra Cates, Andrew Yoo, Anna Moszczynska, Ting Wang, Bo Zhang

Open Access Publications

No abstract provided.

Combination Of Dasatinib With Chemotherapy In Previously Untreated Core Binding Factor Acute Myeloid Leukemia: Calgb 10801, Guido Marcucci, Geoffrey L. Uy, Et Al.

Open Access Publications

No abstract provided.

Kir B Donors Improve The Outcome For Aml Patients Given Reduced Intensity Conditioning And Unrelated Donor Transplantation, Daniel Weisdorf, Todd A. Fehniger, Et Al.

Open Access Publications

No abstract provided.

Atypical Cadherin Fat4 Orchestrates Lymphatic Endothelial Cell Polarity In Response To Flow, Kelly L Betterman, Drew L Sutton, Genevieve A Secker, Jan Kazenwadel, Anna Oszmiana, Lillian Lim, Naoyuki Miura, Lydia Sorokin, Benjamin M Hogan, Mark L Kahn, Helen Mcneill, Natasha L Harvey

Open Access Publications

The atypical cadherin FAT4 has established roles in the regulation of planar cell polarity and Hippo pathway signaling that are cell context dependent. The recent identification of FAT4 mutations in Hennekam syndrome, features of which include lymphedema, lymphangiectasia, and mental retardation, uncovered an important role for FAT4 in the lymphatic vasculature. Hennekam syndrome is also caused by mutations in collagen and calcium binding EGF domains 1 (CCBE1) and ADAM metallopeptidase with thrombospondin type 1 motif 3 (ADAMTS3), encoding a matrix protein and protease, respectively, that regulate activity of the key prolymphangiogenic VEGF-C/VEGFR3 signaling axis by facilitating the proteolytic cleavage and …

Influence Of Adiposity, Insulin Resistance, And Intrahepatic Triglyceride Content On Insulin Kinetics, Gordon I Smith, David C Polidori, Mihoko Yoshino, Monica L Kearney, Bruce W Patterson, Bettina Mittendorfer, Samuel Klein

Open Access Publications

BACKGROUNDInsulin is a key regulator of metabolic function. The effects of excess adiposity, insulin resistance, and hepatic steatosis on the complex integration of insulin secretion and hepatic and extrahepatic tissue extraction are not clear.METHODSA hyperinsulinemic-euglycemic clamp and a 3-hour oral glucose tolerance test were performed to evaluate insulin sensitivity and insulin kinetics after glucose ingestion in 3 groups: (a) lean subjects with normal intrahepatic triglyceride (IHTG) and glucose tolerance (lean-NL; n = 14), (b) obese subjects with normal IHTG and glucose tolerance (obese-NL; n = 24), and (c) obese subjects with nonalcoholic fatty liver disease (NAFLD) and prediabetes (obese-NAFLD; n …

Inhibition Of The Translesion Synthesis Polymerase Rev1 Exploits Replication Gaps As A Cancer Vulnerability, Sumeet Nayak, Jennifer A Calvo, Ke Cong, Min Peng, Emily Berthiaume, Jessica Jackson, Angela M Zaino, Alessandro Vindigni, M Kyle Hadden, Sharon B Cantor

Open Access Publications

The replication stress response, which serves as an anticancer barrier, is activated not only by DNA damage and replication obstacles but also oncogenes, thus obscuring how cancer evolves. Here, we identify that oncogene expression, similar to other replication stress-inducing agents, induces single-stranded DNA (ssDNA) gaps that reduce cell fitness. DNA fiber analysis and electron microscopy reveal that activation of translesion synthesis (TLS) polymerases restricts replication fork slowing, reversal, and fork degradation without inducing replication gaps despite the continuation of replication during stress. Consistent with gap suppression (GS) being fundamental to cancer, we demonstrate that a small-molecule inhibitor targeting the TLS …

Contacting Domains Segregate A Lipid Transporter From A Solute Transporter In The Malarial Host–Parasite Interface, Matthias Garten, Josh R. Beck, Robyn Roth, Tatyana Tenkova-Heuser, John Heuser, Eva S. Istvan, Christopher K.E. Bleck, Daniel E. Goldberg, Joshua Zimmerberg

Open Access Publications

No abstract provided.

Deployment Of Convalescent Plasma For The Prevention And Treatment Of Covid-19, Evan M Bloch, Brenda J Grossman, Jeffrey P Henderson, Et Al

Open Access Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), has spurred a global health crisis. To date, there are no proven options for prophylaxis for those who have been exposed to SARS-CoV-2, nor therapy for those who develop COVID-19. Immune (i.e., "convalescent") plasma refers to plasma that is collected from individuals following resolution of infection and development of antibodies. Passive antibody administration through transfusion of convalescent plasma may offer the only short-term strategy for conferring immediate immunity to susceptible individuals. There are numerous examples in which convalescent plasma has been used successfully as postexposure prophylaxis …

The Clonal Evolution Of Metastatic Colorectal Cancer, Ha X Dang, Bradley A Krasnick, Julie G Grossman, Matthew S Strand, Jin Zhang, Christopher A Miller, Robert S Fulton, S Peter Goedegebuure, Catrina C Fronick, Malachi Griffith, David E Larson, Brian D Goetz, Jason R Walker, William G Hawkins, Steven M Strasberg, Kian H Lim, Timothy J Ley, Christopher A Maher, Ryan C Fields, Et Al

Open Access Publications

Tumor heterogeneity and evolution drive treatment resistance in metastatic colorectal cancer (mCRC). Patient-derived xenografts (PDXs) can model mCRC biology; however, their ability to accurately mimic human tumor heterogeneity is unclear. Current genomic studies in mCRC have limited scope and lack matched PDXs. Therefore, the landscape of tumor heterogeneity and its impact on the evolution of metastasis and PDXs remain undefined. We performed whole-genome, deep exome, and targeted validation sequencing of multiple primary regions, matched distant metastases, and PDXs from 11 patients with mCRC. We observed intricate clonal heterogeneity and evolution affecting metastasis dissemination and PDX clonal selection. Metastasis formation followed …

Mapping Of The Language Network With Deep Learning, Patrick Luckett, John J Lee, Ki Yun Park, Donna Dierker, Andy G S Daniel, Benjamin A Seitzman, Carl D Hacker, Beau M Ances, Eric C Leuthardt, Abraham Z Snyder, Joshua S Shimony

Open Access Publications

No abstract provided.

Site-1 Protease Ablation In The Osterix-Lineage In Mice Results In Bone Marrow Neutrophilia And Hematopoietic Stem Cell Alterations, Debabrata Patra, Joongho Kim, Qiang Zhang, Eric Tycksen, Linda J Sandell

Open Access Publications

Site-1 protease (S1P) ablation in the osterix-lineage in mice drastically reduces bone development and downregulates bone marrow-derived skeletal stem cells. Here we show that these mice also suffer from spina bifida occulta with a characteristic lack of bone fusion in the posterior neural arches. Molecular analysis of bone marrow-derived non-red blood cell cells, via single-cell RNA-Seq and protein mass spectrometry, demonstrate that these mice have a much-altered bone marrow with a significant increase in neutrophils and

Deep Learning Assessment Of Breast Terminal Duct Lobular Unit Involution: Towards Automated Prediction Of Breast Cancer Risk, Suzanne C. Wetstein, Ying Liu, Et Al.

Open Access Publications

Terminal duct lobular unit (TDLU) involution is the regression of milk-producing structures in the breast. Women with less TDLU involution are more likely to develop breast cancer. A major bottleneck in studying TDLU involution in large cohort studies is the need for labor-intensive manual assessment of TDLUs. We developed a computational pathology solution to automatically capture TDLU involution measures. Whole slide images (WSIs) of benign breast biopsies were obtained from the Nurses' Health Study. A set of 92 WSIs was annotated for acini, TDLUs and adipose tissue to train deep convolutional neural network (CNN) models for detection of acini, and …

12-Lox Catalyzes The Oxidation Of 2-Arachidonoyl-Lysolipids In Platelets Generating Eicosanoid-Lysolipids That Are Attenuated By Ipla2Γ Knockout, Xinping Liu, Harold F. Sims, Christopher M. Jenkins, Shaoping Guan, Beverly G. Dilthey, Richard W. Gross

Open Access Publications

No abstract provided.

Tumor-Associated Macrophages In Osteosarcoma: From Mechanisms To Therapy, Francesca Cersosimo, Silvia Lonardi, Giulia Bernardini, Brian Telfer, Giulio Eugenio Mandelli, Annalisa Santucci, William Vermi, Emanuele Giurisato

Open Access Publications

Osteosarcomas (OSs) are bone tumors most commonly found in pediatric and adolescent patients characterized by high risk of metastatic progression and recurrence after therapy. Effective therapeutic management of this disease still remains elusive as evidenced by poor patient survival rates. To achieve a more effective therapeutic management regimen, and hence patient survival, there is a need to identify more focused targeted therapies for OSs treatment in the clinical setting. The role of the OS tumor stroma microenvironment plays a significant part in the development and dissemination of this disease. Important components, and hence potential targets for treatment, are the tumor-infiltrating …

Mutualist And Pathogen Traits Interact To Affect Plant Community Structure In A Spatially Explicit Model, John W. Schroeder, Andrew Dobson, Scott A. Mangan, Daniel F. Petticord, Edward Allen Herre

Open Access Publications

No abstract provided.

Modeling Biological And Genetic Diversity In Upper Tract Urothelial Carcinoma With Patient Derived Xenografts, Kwanghee Kim, James J. Hsieh, Et Al.

Open Access Publications

No abstract provided.

Core Warming Of Coronavirus Disease 2019 (Covid-19) Patients Undergoing Mechanical Ventilation-A Protocol For A Randomized Controlled Pilot Study, Nathaniel Bonfanti, Emily Gundert, Anne M. Drewry, Kristina Goff, Roger Bedimo, Erik Kulstad

Open Access Publications

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by the virus SARS-CoV-2, is spreading rapidly across the globe, with little proven effective therapy. Fever is seen in most cases of COVID-19, at least at the initial stages of illness. Although fever is typically treated (with antipyretics or directly with ice or other mechanical means), increasing data suggest that fever is a protective adaptive response that facilitates recovery from infectious illness.

OBJECTIVE: To describe a randomized controlled pilot study of core warming patients with COVID-19 undergoing mechanical ventilation.

METHODS: This prospective single-site randomized controlled pilot study will enroll 20 patients undergoing mechanical ventilation …

Pif1, Rpa, And Fen1 Modulate The Ability Of Dna Polymerase Δ To Overcome Protein Barriers During Dna Synthesis, Melanie A. Sparks, Peter M. Burgers, Roberto Galletto

Open Access Publications

No abstract provided.

Assaying Three-Dimensional Cellular Architecture Using X-Ray Tomographic And Correlated Imaging Approaches, Peter O. Bayguinov, Max R. Fisher, James A. J. Fitzpatrick

Open Access Publications

No abstract provided.

Complications And Patient-Reported Outcomes After Tram And Diep Flaps: A Systematic Review And Meta-Analysis, Waverly Y. He, Leen El Eter, Pooja Yesantharao, Bethany Hung, Haley Owens, Sarah Persing, Justin M. Sacks

Open Access Publications

No abstract provided.

Tetracycline-Inactivating Enzymes From Environmental, Human Commensal, And Pathogenic Bacteria Cause Broad-Spectrum Tetracycline Resistance, Andrew J. Gasparrini, Jana L. Markley, Hirdesh Kumar, Bin Wang, Luting Fang, Sidra Irum, Chanez T. Symister, Meghan Wallace, Carey-Ann D. Burnham, Saadia Andleeb, Niraj H. Tolia, Timothy A. Wencewicz, Gautam Dantas

Open Access Publications

No abstract provided.

E Proteins Orchestrate Dynamic Transcriptional Cascades Implicated In The Suppression Of The Differentiation Of Group 2 Innate Lymphoid Cells, Vincent Peng, Constantin Georgescu, Anna Bakowska, Aneta Pankow, Liangyue Qian, Jonathan D. Wren, Xiao-Hong Sun

Open Access Publications

No abstract provided.

Cockayne Syndrome: The Many Challenges And Approaches To Understand A Multifaceted Disease, Alexandre Teixeira Vessoni, Camila Chaves Coelho Guerra, Gustavo Satoru Kajitani, Livia Luz Souza Nascimento, Camila Carrião Machado Garcia

Open Access Publications

The striking and complex phenotype of Cockayne syndrome (CS) patients combines progeria-like features with developmental deficits. Since the establishment of the in vitro culture of skin fibroblasts derived from patients with CS in the 1970s, significant progress has been made in the understanding of the genetic alterations associated with the disease and their impact on molecular, cellular, and organismal functions. In this review, we provide a historic perspective on the research into CS by revisiting seminal papers in this field. We highlighted the great contributions of several researchers in the last decades, ranging from the cloning and characterization of CS …

Assessment Of Plasma Amyloid-Β42/40 And Cognitive Decline Among Community-Dwelling Older Adults, Kelly Virecoulon Giudici, Philipe De Souto Barreto, Sophie Guyonnet, Yan Li, Randall J. Bateman, Bruno Vellas

Open Access Publications

Importance: Plasma measurement of amyloid-β (Aβ) peptides has been associated with cognitive function, but evidence of its ability to identify cognitive decline is still scarce.

Objective: To investigate the associations between plasma Aβ42/40 and cognitive decline over time among community-dwelling older adults with subjective memory concerns.

Design, Setting, and Participants: This multicenter cohort study used data from volunteers in the 5-year study Multidomain Alzheimer Preventive Trial (MAPT). Participants were aged 70 years or older and observed for a median (interquartile range) of 3.9 (2.0-4.0) years. Recruitment of participants started in May 2008 and ended in February 2011. Follow-up ended in …

The Genetic Architecture Of Sporadic And Multiple Consecutive Miscarriage, Triin Laisk, Avinash Ramu, Donald F. Conrad, Et Al.

Open Access Publications

No abstract provided.

The Landscape Of Novel Therapeutics And Challenges In Glioblastoma Multiforme: Contemporary State And Future Directions, Karam Khaddour, Tanner M Johanns, George Ansstas

Open Access Publications

BACKGROUND: Glioblastoma multiforme is a malignant intracranial neoplasm that constitutes a therapeutic challenge because of the associated high morbidity and mortality given the lack of effective approved medication and aggressive nature of the tumor. However, there has been extensive research recently to address the reasons implicated in the resistant nature of the tumor to pharmaceutical compounds, which have resulted in several clinical trials investigating promising treatment approaches.

METHODS: We reviewed literature published since 2010 from PUBMED and several annual meeting abstracts through 15 September 2020. Selected articles included those relevant to topics of glioblastoma tumor biology, original basic research, clinical …

Association Between Intake Of Energy And Macronutrients And Memory Impairment Severity In Us Older Adults, National Health And Nutrition Examination Survey 2011-2014, Qinran Liu, Jianjun Guo, Liang Hu, Nicola Veronese, Lee Smith, Lin Yang, Chao Cao

Open Access Publications

Without a cure, dementia affects about 50 million people worldwide. Understanding the effects of dietary habits, a key lifestyle behavior, on memory impairment is critical to inform early behavioral modification to delay further memory loss and progression to dementia. We examined the associations of total energy intake and energy intake from macronutrients with memory impairment among older US adults using data from the nationally representative National Health and Nutrition Examination Survey study 2011-2014. A total of 3623 participants aged ≥60 years were analyzed. Comparing to those with low total energy intake, individuals with high intake were more likely to have …

Radiolabeled 6-(2, 3-Dichlorophenyl)-N4-Methylpyrimidine-2, 4-Diamine (Th287): A Potential Radiotracer For Measuring And Imaging Mth1, Huaping Chen, Sadia Afrin, Yingqiu Guo, Wenhua Chu, Tammie L S Benzinger, Buck E Rogers, Joel R Garbow, Joel S Perlmutter, Dong Zhou, Jinbin Xu

Open Access Publications

MTH1 (MutT homolog 1) or NUDT1 (Nudix Hydrolase 1), also known as oxidized purine nucleoside triphosphatase, has potential as a biomarker for monitoring cancer progression and quantifying target engagement for relevant therapies. In this study, we validate one MTH1 inhibitor TH287 as a PET MTH1 radiotracer. TH287 was radiolabeled with tritium and the binding of [