Digital Commons Network^™

Staging Of The Axilla In Breast Cancer And The Evolving Role Of Axillary Ultrasound, Michael Y Chen, William E Gillanders

Open Access Publications

Axillary lymph nodes have long been recognized as a route for breast cancer to spread systemically. As a result, staging of the axilla has always played a central role in the treatment of breast cancer. Anatomic staging was believed to be important for two reasons: 1) it predicts prognosis and guides medical therapy, and 2) it is a potential therapy for removal of disease in the axilla. This paradigm has now been called into question. Prognostic information is driven increasingly by tumor biology, and trials such as the ACOSOG Z0011 demonstrates removal of axillary disease is not therapeutic. Staging of …

Regulation Of Beta-Amyloid Production In Neurons By Astrocyte-Derived Cholesterol, Hao Wang, Joshua A. Kulas, Chao Wang, David M. Holtzman, Heather A. Ferris, Scott B. Hansen

Open Access Publications

No abstract provided.

Critical Roles Of Calpastatin In Ischemia/Reperfusion Injury In Aged Livers, Joseph Flores-Toro, Sung-Kook Chun, Jun-Kyu Shin, Joan Campbell, Melissa Lichtenberger, William Chapman, Ivan Zendejas, Kevin Behrns, Christiaan Leeuwenburgh, Jae-Sung Kim

Open Access Publications

Ischemia/reperfusion (I/R) injury unavoidably occurs during hepatic resection and transplantation. Aged livers poorly tolerate I/R during surgical treatment. Although livers have a powerful endogenous inhibitor of calpains, calpastatin (CAST), I/R activates calpains, leading to impaired autophagy, mitochondrial dysfunction, and hepatocyte death. It is unknown how I/R in aged livers affects CAST. Human and mouse liver biopsies at different ages were collected during in vivo I/R. Hepatocytes were isolated from 3-month- (young) and 26-month-old (aged) mice, and challenged with short in vitro simulated I/R. Cell death, protein expression, autophagy, and mitochondrial permeability transition (MPT) between the two age groups were compared. …

Ngn3-Positive Cells Arise From Pancreatic Duct Cells, Chiemi Kimura-Nakajima, Kousuke Sakaguchi, Yoshiko Hatano, Masahito Matsumoto, Yasushi Okazaki, Keisuke Tanaka, Takumi Yamane, Yuichi Oishi, Kenji Kamimoto, Ken Iwatsuki

Open Access Publications

The production of pancreatic β cells is the most challenging step for curing diabetes using next-generation treatments. Adult pancreatic endocrine cells are thought to be maintained by the self-duplication of differentiated cells, and pancreatic endocrine neogenesis can only be observed when the tissue is severely damaged. Experimentally, this can be performed using a method named partial duct ligation (PDL). As the success rate of PDL surgery is low because of difficulties in identifying the pancreatic duct, we previously proposed a method for fluorescently labeling the duct in live animals. Using this method, we performed PDL on neurogenin3 (Ngn3)-GFP transgenic mice …

Emerging Genotype-Phenotype Relationships In Primary Ciliary Dyskinesia, Steven K Brennan, Thomas W Ferkol, Stephanie D Davis

Open Access Publications

Primary ciliary dyskinesia (PCD) is a rare inherited condition affecting motile cilia and leading to organ laterality defects, recurrent sino-pulmonary infections, bronchiectasis, and severe lung disease. Research over the past twenty years has revealed variability in clinical presentations, ranging from mild to more severe phenotypes. Genotype and phenotype relationships have emerged. The increasing availability of genetic panels for PCD continue to redefine these genotype-phenotype relationships and reveal milder forms of disease that had previously gone unrecognized.

Recent Advances On Extracellular Vesicles In Central Nervous System Diseases, Tao Jin, Jiachen Gu, Zongshan Li, Zhongping Xu, Yaxing Gui

Open Access Publications

Extracellular vesicles (EVs) are particles released by multiple cells, encapsulated by lipid bilayers and containing a variety of biological materials, including proteins, nucleic acids, lipids and metabolites. With the advancement of separation and characterization methods, EV subtypes and their complex and diverse functions have been recognized. In the central nervous system (CNS), EVs are involved in various physiological and pathological processes, such as regulation of neuronal firing, synaptic plasticity, formation and maintenance of myelin sheath, propagation of neuroinflammation, neuroprotection, and spread and removal of toxic protein aggregates. Activity-dependent alteration of constituents enables EVs to reflect the change of cell and …

A Mouse Model Displays Host And Bacterial Strain Differences In Aerococcus Urinae Urinary Tract Infection, Nicole M Gilbert, Brian Choi, Jingjie Du, Christina Collins, Amanda L Lewis, Catherine Putonti, Alan J Wolfe

Open Access Publications

In recent years, the clinical significance of Aerococcus urinae has been increasingly recognized. A. urinae has been implicated in cases of urinary tract infection (UTI; acute cystitis and pyelonephritis) in both male and female patients, ranging from children to older adults. Aerococcus urinae can also be invasive, causing urosepsis, endocarditis, and musculoskeletal infections. Mechanisms of pathogenesis in A. urinae infections are poorly understood, largely due to the lack of an animal model system. In response to this gap, we developed a model of A. urinae urinary tract infection in mice. We compared A. urinae UTI in female C3H/HeN and C57BL/6 …

Functional And Epigenetic Phenotypes Of Humans And Mice With Dnmt3a Overgrowth Syndrome, Amanda M. Smith, Taylor A. Lavalle, Marwan Shinawi, Sai M. Ramakrishnan, Haley J. Abel, Cheryl A. Hill, Nicole M. Kirkland, Michael P. Rettig, Nichole M. Helton, Sharon E. Heath, Francesca Ferraro, David Y. Chen, Sangeeta Adak, Clay F. Semenkovich, Diana L. Christian, Jenna R. Martin, Harrison W. Gabel, Christopher A. Miller, Timothy J. Ley

Open Access Publications

No abstract provided.

Icam1 Initiates Ctc Cluster Formation And Trans-Endothelial Migration In Lung Metastasis Of Breast Cancer, Rokana Taftaf, Andrew A. Davis, Et Al

Open Access Publications

No abstract provided.

Influence Of Mpv17 On Hair-Cell Mitochondrial Homeostasis, Synapse Integrity, And Vulnerability To Damage In The Zebrafish Lateral Line, Melanie Holmgren, Lavinia Sheets

Open Access Publications

Noise exposure is particularly stressful to hair-cell mitochondria, which must produce enough energy to meet high metabolic demands as well as regulate local intracellular Ca

Development Of A Library Of Laminin-Mimetic Peptide Hydrogels For Control Of Nucleus Pulposus Cell Behaviors, Julie E Speer, Marcos N Barcellona, Michael Y Lu, Zizhen Zha, Liufang Jing, Munish C Gupta, Jacob M Buchowski, Michael P Kelly, Lori A Setton

Open Access Publications

The nucleus pulposus (NP) of the intervertebral disc plays a critical role in distributing mechanical loads to the axial skeleton. Alterations in NP cells and, consequently, NP matrix are some of the earliest changes in the development of disc degeneration. Previous studies demonstrated a role for laminin-presenting biomaterials in promoting a healthy phenotype for human NP cells from degenerated tissue. Here we investigate the use of laminin-mimetic peptides presented individually or in combination on a poly(ethylene) glycol hydrogel as a platform to modulate the behaviors of degenerative human NP cells. Data confirm that NP cells attach to select laminin-mimetic peptides …

Nivolumab Plus Cabozantinib Versus Sunitinib For Advanced Renal-Cell Carcinoma, Toni K. Choueiri, James J. Hsieh, Et Al

Open Access Publications

No abstract provided.

Deletion Of Glut1 In Early Postnatal Cartilage Reprograms Chondrocytes Toward Enhanced Glutamine Oxidation, Cuicui Wang, Jun Ying, Xiangfeng Niu, Xiaofei Li, Gary J. Patti, Jie Shen, Regis J. O'Keefe

Open Access Publications

No abstract provided.

Mycobacterium Tuberculosis Rv3160c Is Atetr‑Like Transcriptional Repressor That Regulates Expression Of The Putative Oxygenase Rv3161c, Hasan Tükenmez, Souvik Sarkar, Saber Anoosheh, Anastasiia Kruchanova, Isabel Edström, Gregory A. Harrison, Christina L. Stallings, Fredrik Almqvist, Christer Larsson

Open Access Publications

No abstract provided.

Specifications Of The Variant Curation Guidelines For Itga2b/Itgb3: Clingen Platelet Disorder Variant Curation Panel, Justyne E. Ross, Jorge Di Paola, Et Al.

Open Access Publications

No abstract provided.

Genome-Wide Meta-Analysis Of Muscle Weakness Identifies 15 Susceptibility Loci In Older Men And Women, Garan Jones, Mary K. Wojczynski, Et Al.

Open Access Publications

No abstract provided.

Sequence- And Structure-Specific Cytosine-5 Mrna Methylation By Nsun6, Tommaso Selmi, Shobbir Hussain, Sabine Dietmann, Matthias Heiß, Kayla Borland, Sophia Flad, Jean-Michel Carter, Rebecca Dennison, Ya-Lin Huang, Stefanie Kellner, Susanne Bornelöv, Michaela Frye

Open Access Publications

The highly abundant N6-methyladenosine (m6A) RNA modification affects most aspects of mRNA function, yet the precise function of the rarer 5-methylcytidine (m5C) remains largely unknown. Here, we map m5C in the human transcriptome using methylation-dependent individual-nucleotide resolution cross-linking and immunoprecipitation (miCLIP) combined with RNA bisulfite sequencing. We identify NSUN6 as a methyltransferase with strong substrate specificity towards mRNA. NSUN6 primarily targeted three prime untranslated regions (3'UTR) at the consensus sequence motif CTCCA, located in loops of hairpin structures. Knockout and rescue experiments revealed enhanced mRNA and translation levels when NSUN6-targeted mRNAs were methylated. Ribosome profiling further demonstrated that NSUN6-specific methylation …

Breast Cancer Mortality Hot Spots Among Black Women With De Novo Metastatic Breast Cancer, Yunan Han, Marvin Langston, Lindsay Fuzzell, Saira Khan, Marquita W. Lewis-Thames, Graham A. Colditz, Justin Xavier Moore

Open Access Publications

Background: Black women living in southern states have the highest breast cancer mortality rate in the United States. The prognosis of de novo metastatic breast cancer is poor. Given these mortality rates, we are the first to link nationally representative data on breast cancer mortality hot spots (counties with high breast cancer mortality rates) with cancer mortality data in the United States and investigate the association of geographic breast cancer mortality hot spots with de novo metastatic breast cancer mortality among Black women.

Methods: We identified 7292 Black women diagnosed with de novo metastatic breast cancer in Surveillance, Epidemiology, and …

Complexity In Genetic Cardiomyopathies And New Approaches For Mechanism-Based Precision Medicine, Michael J. Greenberg, Jil C. Tardiff

Open Access Publications

Genetic cardiomyopathies have been studied for decades, and it has become increasingly clear that these progressive diseases are more complex than originally thought. These complexities can be seen both in the molecular etiologies of these disorders and in the clinical phenotypes observed in patients. While these disorders can be caused by mutations in cardiac genes, including ones encoding sarcomeric proteins, the disease presentation varies depending on the patient mutation, where mutations even within the same gene can cause divergent phenotypes. Moreover, it is challenging to connect the mutation-induced molecular insult that drives the disease pathogenesis with the various compensatory and …

Evaluation Of The Neonatal Sequential Organ Failure Assessment And Mortality Risk In Preterm Infants With Late-Onset Infection, Noa Fleiss, Angela N. Lewis, Krista E. Cooksey, Ameena N. Husain, Misty Good, Et Al

Open Access Publications

Importance: Infection in neonates remains a substantial problem. Advances for this population are hindered by the absence of a consensus definition for sepsis. In adults, the Sequential Organ Failure Assessment (SOFA) operationalizes mortality risk with infection and defines sepsis. The generalizability of the neonatal SOFA (nSOFA) for neonatal late-onset infection-related mortality remains unknown.

Objective: To determine the generalizability of the nSOFA for neonatal late-onset infection-related mortality across multiple sites.

Design, Setting, and Participants: A multicenter retrospective cohort study was conducted at 7 academic neonatal intensive care units between January 1, 2010, and December 31, 2019. Participants included 653 preterm ( …

The Catalytic Mechanism Of Vitamin K Epoxide Reduction In Acellular Environment, Guomin Shen, Weidong Cui, Qing Cao, Meng Gao, Hongli Liu, Gaigai Su, Michael L. Gross, Weikai Li

Open Access Publications

No abstract provided.

The Association Of Polygenic Risk For Schizophrenia, Bipolar Disorder, And Depression With Neural Connectivity In Adolescents And Young Adults: Examining Developmental And Sex Differences, J.L. Meyers, E.C. Johnson, A. Agrawal, A. Anokhin, M.H. Plawecki, Et Al.

Open Access Publications

No abstract provided.

Intracranial Delivery Of Aav9 Gene Therapy Partially Prevents Retinal Degeneration And Visual Deficits In Cln6-Batten Disease Mice, Katherine A. White, Hemanth R. Nelvagal, Timothy A. Poole, Bin Lu, Tyler B. Johnson, Samantha Davis, Melissa A. Pratt, Jon Brudvig, Ana B. Assis, Shibi Likhite, Kathrin Meyer, Brian K. Kaspar, Jonathan D. Cooper, Shaomei Wang, Jill M. Weimer

Open Access Publications

No abstract provided.

Effects Of Dietary Restriction On Neuroinflammation In Neurodegenerative Diseases, Luigi Fontana, Laura Ghezzi, Anne H. Cross, Laura Piccio

Open Access Publications

Recent and accumulating work in experimental animal models and humans shows that diet has a much more pervasive and prominent role than previously thought in modulating neuroinflammatory and neurodegenerative mechanisms leading to some of the most common chronic central nervous system (CNS) diseases. Chronic or intermittent food restriction has profound effects in shaping brain and peripheral metabolism, immunity, and gut microbiome biology. Interactions among calorie intake, meal frequency, diet quality, and the gut microbiome modulate specific metabolic and molecular pathways that regulate cellular, tissue, and organ homeostasis as well as inflammation during normal brain aging and CNS neurodegenerative diseases, including …

Chemoprevention Agents To Reduce Mammographic Breast Density In Premenopausal Women: A Systematic Review Of Clinical Trials, Ana S. Salazar, Malika Rakhmankulova, Laura E. Simon, Adetunji T. Toriola

Open Access Publications

Background: Higher mammographic breast density (MBD) is associated with an increased risk of breast cancer when compared with lower MBD, especially in premenopausal women. However, little is known about the effectiveness of chemoprevention agents in reducing MBD in premenopausal women without a history of breast cancer. Findings from this review should provide insight on how to target MBD in breast cancer prevention in premenopausal women with dense breasts.

Methods: We searched 9 electronic databases for clinical trials in English, Spanish, French, or German published until January 2020. Articles evaluating the association of pharmacological agents and MBD were included. Data were …

Ash Isth Nhf Wfh 2021 Guidelines On The Diagnosis Of Von Willebrand Disease, Paula D. James, Jorge Di Paola, Et Al.

Open Access Publications

No abstract provided.

Impaired Eif5a Function Causes A Mendelian Disorder That Is Partially Rescued In Model Systems By Spermidine, Victor Faundes, Jorge L. Granadillo, Et Al.

Open Access Publications

No abstract provided.

Diffusion Histology Imaging Differentiates Distinct Pediatric Brain Tumor Histology, Zezhong Ye, Komal Srinivasa, Ashely Meyer, Peng Sun, Joshua Lin, Jeffrey D. Viox, Chunyu Song, Anthony T. Wu, Sheng-Kwei Song, Sonika Dahiya, Joshua B. Rubin

Open Access Publications

No abstract provided.

Targeting Primary And Metastatic Uveal Melanoma With A G Protein Inhibitor, Michael D. Onken, Carol M. Makepeace, Kevin M. Kaltenbronn, Joelle Choi, Leonel Hernandez-Aya, Katherine N. Weilbaecher, Kisha D. Piggott, P. Kumar Rao, Carla M. Yuede, Alethia J. Dixon, Patrick Osei-Owusu, John A. Cooper, Kendall J. Blumer

Open Access Publications

No abstract provided.

Glucosamine And Chondroitin Use In Relation To C-Reactive Protein Concentration: Results By Supplement Form, Formulation, And Dose, Elizabeth D. Kantor, Kelli O'Connell, Mengmeng Du, Chao Cao, Xuehong Zhang, Dong Hoon Lee, Yin Cao, Edward L. Giovannucci

Open Access Publications

No abstract provided.