Digital Commons Network^™

Closed-Loop Acoustic Stimulation During Sedation With Dexmedetomidine (Class-D): Protocol For A Within-Subject, Crossover, Controlled, Interventional Trial With Healthy Volunteers, Christian S Guay, Alyssa K Labonte, Michael C Montana, Eric C Landsness, Brendan P Lucey, Mohammadmehdi Kafashan, Simon Haroutounian, Michael S Avidan, Emery N Brown, Ben Julian A Palanca

Open Access Publications

Introduction: The relative power of slow-delta oscillations in the electroencephalogram (EEG), termed slow-wave activity (SWA), correlates with level of unconsciousness. Acoustic enhancement of SWA has been reported for sleep states, but it remains unknown if pharmacologically induced SWA can be enhanced using sound. Dexmedetomidine is a sedative whose EEG oscillations resemble those of natural sleep. This pilot study was designed to investigate whether SWA can be enhanced using closed-loop acoustic stimulation during sedation (CLASS) with dexmedetomidine.

Methods: Closed-Loop Acoustic Stimulation during Sedation with Dexmedetomidine (CLASS-D) is a within-subject, crossover, controlled, interventional trial with healthy volunteers. Each participant will be sedated …

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 …

The American Society Of Pain And Neuroscience (Aspn) Practical Guidelines To Study Design And Scientific Manuscript Preparation In Neuromodulation, Yashar Eshraghi, Krishnan Chakravarthy, Natalie H Strand, Prasad Shirvalkar, Nathaniel M Schuster, Rany T Abdallah, Ricardo Vallejo, Dawood Sayed, David Kim, Chong Kim, Kathleen Meacham, Timothy Deer, Translational Research Committee American Society Of Pain And Neuroscience (Aspn)

Open Access Publications

Background: Healthcare clinical and even policy decisions are progressively made based on research-based evidence. The process by which the appropriate trials are developed and well-written manuscripts by means of evidence-based medicine recommendations has resulted in unprecedented necessity in evidence-based medicine in neuromodulation.

Methods: The essential considerations in the planning of neuromodulation research are discussed in the light of available scientific literature as well as the authors' scientific expertise regarding research study design and scientific manuscript preparation.

Conclusion: This article should enable the reader to understand how to appropriately design a clinical research study and prepare scientific manuscripts. The high-quality and …

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.

Home Hazard Removal To Reduce Falls Among Community-Dwelling Older Adults: A Randomized Clinical Trial, Susan Stark, Marian Keglovits, Emily Somerville, Yi-Ling Hu, Abigail Barker, Dave Sykora, Yan Yan

Open Access Publications

Importance: Falls are the leading preventable cause of morbidity, mortality, and premature institutionalization for community-dwelling older adults.

Objective: To test the effectiveness of a behavioral intervention on fall risk among older adults receiving services from an Area Agency on Aging.

Design, Setting, and Participants: This randomized clinical trial examined a home hazard removal intervention in the community using a race- and sex-stratified randomization design. Older adults receiving services from the Area Agency on Aging in urban St Louis, Missouri, were assigned to a home hazard removal intervention delivered over 2 weeks with a 6-month booster or usual care control. Eligible …

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 (

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 …

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 …

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 …