Digital Commons Network^™

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. …

Parallel Hippocampal-Parietal Circuits For Self- And Goal-Oriented Processing, Annie Zheng, David F. Montez, Scott Marek, Adrian W. Gilmore, Dillan J. Newbold, Timothy O. Laumann, Benjamin P. Kay, Nicole A. Seider, Andrew N. Van, Jacqueline M. Hampton, Dimitrios Alexopoulos, Bradley L. Schlaggar, Chad M. Sylvester, Deanna J. Greene, Joshua S. Shimony, Steven M. Nelson, Gagan S. Wig, Caterina Gratton, Kathleen B. Mcdermott, Marcus E. Raichle, Evan M. Gordon, Nico U. F. Dosenbach

Open Access Publications

No abstract provided.

Adult Patient Preferences For Long-Acting Adhd Treatments: A Discrete Choice Experiment, M Janelle Cambron-Mellott, Jaromir Mikl, Joana E Matos, Jennifer G Erensen, Kathleen Beusterien, Marc J Cataldo, Bernadette Hallissey, Gregory W Mattingly

Open Access Publications

Background and Objective: Treatment for attention deficit hyperactivity disorder (ADHD) requires a multifaceted approach including psychosocial interventions and pharmacological treatment. This study evaluates preferences for specific attributes associated with different long-acting stimulant treatment among US adults with ADHD.

Methods: Patients completed an online, cross-sectional survey, incorporating a discrete choice experiment to assess preferences for attributes.

Results: Analyses included 200 adults with ADHD (mean age 33.0 years; 60% self-reporting moderate severity); the mean (SD) Adult ADHD Self-Report Scale-v1.1 score was 45.9 (12.4). Overall, patients valued speed of onset most and risk of rebound least. Three population groups with distinct preferences were …

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 …

Mortality In Hemodialysis Patients With Covid-19, The Effect Of Paricalcitol Or Calcimimetics, María Dolores Arenas Jimenez, Adriana S Dusso, Et Al

Open Access Publications

BACKGROUND: In COVID-19 patients, low serum vitamin D (VD) levels have been associated with severe acute respiratory failure and poor prognosis. In regular hemodialysis (HD) patients, there is VD deficiency and markedly reduced calcitriol levels, which may predispose them to worse outcomes of COVID-19 infection. Some hemodialysis patients receive treatment with drugs for secondary hyperparathyroidism, which have well known pleiotropic effects beyond mineral metabolism. The aim of this study was to evaluate the impact of VD status and the administration of active vitamin D medications, used to treat secondary hyperparathyroidism, on survival in a cohort of COVID-19 positive HD patients. …

Tyk2 In Cancer Metastases: Genomic And Proteomic Discovery, Dana C Borcherding, Kevin He, Neha V Amin, Angela C Hirbe

Open Access Publications

Advances in genomic analysis and proteomic tools have rapidly expanded identification of biomarkers and molecular targets important to cancer development and metastasis. On an individual basis, personalized medicine approaches allow better characterization of tumors and patient prognosis, leading to more targeted treatments by detection of specific gene mutations, overexpression, or activity. Genomic and proteomic screens by our lab and others have revealed tyrosine kinase 2 (

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.

Exploring Social Media Recruitment Strategies And Preliminary Acceptability Of An Mhealth Tool For Teens With Eating Disorders, Erin Kasson, Melissa M Vázquez, Christine Doroshenko, Ellen E Fitzsimmons-Craft, Denise E Wilfley, C Barr Taylor, Patricia A Cavazos-Rehg

Open Access Publications

(1) Background: The current study leveraged social media to connect with teens with EDs to identify population specific characteristics and to gather feedback on an mHealth intervention. (2) Methods: We recruited teens with EDs from social media in two phases: (1) Discovery Group, (2) Testing Group. The Discovery Group (

Advances In Genetic And Molecular Understanding Of Alzheimer's Disease, Laura Ibanez, Carlos Cruchaga, Maria Victoria Fernández

Open Access Publications

Alzheimer's disease (AD) has become a common disease of the elderly for which no cure currently exists. After over 30 years of intensive research, we have gained extensive knowledge of the genetic and molecular factors involved and their interplay in disease. These findings suggest that different subgroups of AD may exist. Not only are we starting to treat autosomal dominant cases differently from sporadic cases, but we could be observing different underlying pathological mechanisms related to the amyloid cascade hypothesis, immune dysfunction, and a tau-dependent pathology. Genetic, molecular, and, more recently, multi-omic evidence support each of these scenarios, which are …

Optical Emission-Based Phantom To Verify Coincidence Of Radiotherapy And Imaging Isocenters On An Mr-Linac, Jacqueline M Andreozzi, Petr Brůža, Jochen Cammin, Daniel A Alexander, Brian W Pogue, Olga Green, David J Gladstone

Open Access Publications

PURPOSE: Demonstrate a novel phantom design using a remote camera imaging method capable of concurrently measuring the position of the x-ray isocenter and the magnetic resonance imaging (MRI) isocenter on an MR-linac.

METHODS: A conical frustum with distinct geometric features was machined out of plastic. The phantom was submerged in a small water tank, and aligned using room lasers on a MRIdian MR-linac (ViewRay Inc., Cleveland, OH). The phantom physical isocenter was visualized in the MR images and related to the DICOM coordinate isocenter. To view the x-ray isocenter, an intensified CMOS camera system (DoseOptics LLC., Hanover, NH) was placed …

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 …

Doctor As Street-Level Bureaucrat, Elvin H. Geng

Open Access Publications

No abstract provided.

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

Severe Maternal Morbidity, Race, And Rurality: Trends Using The National Inpatient Sample, 2012–2017, Alina A. Luke, Kristine Huang, Kathryn J. Lindley, Ebony B. Carter, Karen E. Joynt Maddox

Open Access Publications

No abstract provided.

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.

Current Advances In Digital Cognitive Assessment For Preclinical Alzheimer's Disease, Fredrik Öhman, Jason Hassenstab, David Berron, Michael Schöll, Kathryn V Papp

Open Access Publications

There is a pressing need to capture and track subtle cognitive change at the preclinical stage of Alzheimer's disease (AD) rapidly, cost-effectively, and with high sensitivity. Concurrently, the landscape of digital cognitive assessment is rapidly evolving as technology advances, older adult tech-adoption increases, and external events (i.e., COVID-19) necessitate remote digital assessment. Here, we provide a snapshot review of the current state of digital cognitive assessment for preclinical AD including different device platforms/assessment approaches, levels of validation, and implementation challenges. We focus on articles, grants, and recent conference proceedings specifically querying the relationship between digital cognitive assessments and established biomarkers …

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.

Whole Genome Sequence Analyses Of Egfr In 23,732 People Representing Multiple Ancestries In The Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Bridget M. Lin, Lisa De Las Fuentes, 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 …

Using Lorenz Curves To Measure Racial Inequities In Covid-19 Testing, Aaloke Mody, Kristin Pfeifauf, Elvin H. Geng

Open Access Publications

No abstract provided.

Association Of Immunosuppression And Viral Load With Subcortical Brain Volume In An International Sample Of People Living With Hiv, Talia M. Nir, Beau M. Ances, Et Al

Open Access Publications

Importance: Despite more widely accessible combination antiretroviral therapy (cART), HIV-1 infection remains a global public health challenge. Even in treated patients with chronic HIV infection, neurocognitive impairment often persists, affecting quality of life. Identifying the neuroanatomical pathways associated with infection in vivo may delineate the neuropathologic processes underlying these deficits. However, published neuroimaging findings from relatively small, heterogeneous cohorts are inconsistent, limiting the generalizability of the conclusions drawn to date.

Objective: To examine structural brain associations with the most commonly collected clinical assessments of HIV burden (CD4+ T-cell count and viral load), which are generalizable across demographically and clinically diverse …

Assessment Of Suicide In Japan During The Covid-19 Pandemic Vs Previous Years, Haruka Sakamoto, Masahiro Ishikane, Cyrus Ghaznavi, Peter Ueda

Open Access Publications

Importance: There are concerns that suicide rates may have increased during the coronavirus disease 2019 (COVID-19) pandemic.

Objective: To assess whether suicide rates in Japan increased in April through November 2020 compared with previous years.

Design, Setting, and Participants: This cross-sectional study used national data obtained from the Ministry of Health, Labor and Welfare from 2016 to 2020 on the monthly number of individuals who died of suicide in Japan from January to November of 2016 to 2020.

Exposure: 2020 vs previous years.

Main Outcomes and Measures: The main outcome was monthly suicide rates, calculated as the number of individuals …