Digital Commons Network^™

Markers Of Early Changes In Cognition Across Cohorts Of Adults With Down Syndrome At Risk Of Alzheimer's Disease, Andrew J Aschenbrenner, Jason Hassenstab, Et Al

Open Access Publications

Introduction: Down syndrome (DS), a genetic variant of early onset Alzheimer's disease (AD), lacks a suitable outcome measure for prevention trials targeting pre-dementia stages.

Methods: We used cognitive test data collected in several longitudinal aging studies internationally from 312 participants with DS without dementia to identify composites that were sensitive to change over time. We then conducted additional analyses to provide support for the utility of the composites. The composites were presented to an expert panel to determine the most optimal cognitive battery based on predetermined criteria.

Results: There were common cognitive domains across site composites, which were sensitive to …

A Real-World, Prospective, Multicenter, Single-Arm Observational Study Of Duloxetine In Patients With Major Depressive Disorder Or Generalized Anxiety Disorder, Gyorgy Szekeres, Sandor Rozsa, Peter Dome, Gabor Barsony, Xenia Gonda

Open Access Publications

No abstract provided.

Infiltration By Cxcl10 Secreting Macrophages Is Associated With Antitumor Immunity And Response To Therapy In Ovarian Cancer Subtypes, Laura Ardighieri, William Vermi, Et Al

Open Access Publications

Ovarian carcinomas (OCs) are poorly immunogenic and immune checkpoint inhibitors (ICIs) have offered a modest benefit. In this study, high CD3

Outcome After Acute Ischemic Stroke Is Linked To Sex-Specific Lesion Patterns, Anna K. Bonkhoff, Laura Heitsch, Chia-Ling Phuah, Et Al

Open Access Publications

No abstract provided.

Untargeted Metabolomics And Infrared Ion Spectroscopy Identify Biomarkers For Pyridoxine-Dependent Epilepsy, Udo Fh Engelke, Laura A Jansen, Et Al

Open Access Publications

BackgroundPyridoxine-dependent epilepsy (PDE-ALDH7A1) is an inborn error of lysine catabolism that presents with refractory epilepsy in newborns. Biallelic ALDH7A1 variants lead to deficiency of α-aminoadipic semialdehyde dehydrogenase/antiquitin, resulting in accumulation of piperideine-6-carboxylate (P6C), and secondary deficiency of the important cofactor pyridoxal-5'-phosphate (PLP, active vitamin B6) through its complexation with P6C. Vitamin B6 supplementation resolves epilepsy in patients, but intellectual disability may still develop. Early diagnosis and treatment, preferably based on newborn screening, could optimize long-term clinical outcome. However, no suitable PDE-ALDH7A1 newborn screening biomarkers are currently available.MethodsWe combined the innovative analytical methods untargeted metabolomics and infrared ion spectroscopy to discover …

Dysregulation Of Mannose-6-Phosphate-Dependent Cholesterol Homeostasis In Acinar Cells Mediates Pancreatitis, Olga A Mareninova, Yan Xie, Nicholas O Davidson, Et Al

Open Access Publications

Disordered lysosomal/autophagy pathways initiate and drive pancreatitis, but the underlying mechanisms and links to disease pathology are poorly understood. Here, we show that the mannose-6-phosphate (M6P) pathway of hydrolase delivery to lysosomes critically regulates pancreatic acinar cell cholesterol metabolism. Ablation of the Gnptab gene encoding a key enzyme in the M6P pathway disrupted acinar cell cholesterol turnover, causing accumulation of nonesterified cholesterol in lysosomes/autolysosomes, its depletion in the plasma membrane, and upregulation of cholesterol synthesis and uptake. We found similar dysregulation of acinar cell cholesterol, and a decrease in GNPTAB levels, in both WT experimental pancreatitis and human disease. The …

Neurofibrillary Tau Depositions Emerge With Subthreshold Cerebral Beta-Amyloidosis In Down Syndrome, Matthew D Zammit, Dana L Tudorascu, Charles M Laymon, Sigan L Hartley, Paul A Ellison, Shahid H Zaman, Beau M Ances, Sterling C Johnson, Charles K Stone, Marwan N Sabbagh, Chester A Mathis, William E Klunk, Ann D Cohen, Benjamin L Handen, Bradley T Christian

Open Access Publications

INTRODUCTION: Adults with Down syndrome are genetically predisposed to develop Alzheimer's disease and accumulate beta-amyloid plaques (Aβ) early in life. While Aβ has been heavily studied in Down syndrome, its relationship with neurofibrillary tau is less understood. The aim of this study was to evaluate neurofibrillary tau deposition in individuals with Down syndrome with varying levels of Aβ burden.

METHODS: A total of 161 adults with Down syndrome (mean age = 39.2 (8.50) years) and 40 healthy, non-Down syndrome sibling controls (43.2 (12.6) years) underwent T1w-MRI, [C-11]PiB and [F-18]AV-1451 PET scans. PET images were converted to units of standardized uptake …

Ex Vivo Porcine Model For Robot-Assisted Partial Nephrectomy Simulation At A High-Volume Tertiary Center: Resident Perception And Validation Assessment Using The Global Evaluative Assessment Of Robotic Skills Tool, Alexander K. Chow, Ryan Wong, Steven Monda, Rohit Bhatt, Kenneth G. Sands, Joel Vetter, Niraj Badhiwala, Angelia Declue, Eric H. Kim, Arjun Sivaraman, Ramakrishna Venkatesh, Robert Sherburne Figenshau, Kefu Du

Open Access Publications

No abstract provided.

Family Caregiver Problems In Outpatient Palliative Oncology, Jacquelyn J. Benson, Karla T. Washington, Robin L. Kruse, Debra Parker Oliver, Abigail J. Rolbiecki, George Demiris

Open Access Publications

No abstract provided.

Positive Surgical Margins After Robot-Assisted Partial Nephrectomy Predict Long-Term Oncologic Outcomes For Clinically Localized Renal Masses, B. Malik Wahba, Alexander K. Chow, Kefu Du, Kenneth G. Sands, Alethea G. Paradis, Joel M. Vetter, Ramakrishna Venkatesh, Eric H. Kim, Sam B. Bhayani, R. Sherburne Figenshau

Open Access Publications

No abstract provided.

Study To Enhance Understanding Of Stent-Associated Symptoms: Rationale And Study Design, Charles D. Scales Jr., H. Henry Lai, Alana C. Desai, Jodi A. Antonelli, Naim M. Maalouf, Gregory E. Tasian, Peter P. Reese, Michele Curatolo, Kevin Weinfurt, Hussein R. Al-Khalidi, Hunter Wessells, Ziya Kirkali, Jonathan D. Harper, Niddk Urinary Stone Disease Research Network

Open Access Publications

No abstract provided.

Low-Dose Interleukin-2 And Regulatory T Cell Treatments Attenuate Punctate And Dynamic Mechanical Allodynia In A Mouse Model Of Sciatic Nerve Injury, Rong Hu, Jintao Zhang, Xuemei Liu, Dong Huang, Yu-Qing Cao

Open Access Publications

Purpose: Nerve injury-induced mechanical hyper-sensitivity, in particular stroking-induced dynamic allodynia, is highly debilitating and difficult to treat. Previous studies indicate that the immunosuppressive regulatory T (Treg) cells modulate the magnitude of punctate mechanical allodynia resulting from sciatic nerve injury. However, whether enhancing Treg-mediated suppression attenuates dynamic allodynia is not known. In the present study, we addressed this knowledge gap by treating mice with low-dose interleukin-2 (ld-IL2) injections or adoptive transfer of Treg cells.

Methods: Female Swiss Webster mice received daily injections of ld-IL2 (1 μg/mouse, intraperitoneally) either before or after unilateral spared nerve injury (SNI). Male C57BL/6J mice received adoptive …

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 …

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. …

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 (

Doctor As Street-Level Bureaucrat, Elvin H. Geng

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 …

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 …

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 …

Best Practices For Fnirs Publications, Meryem A. Yücel, Joseph Culver, Adam Eggebrecht, Et Al.

Open Access Publications

No abstract provided.

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.

Sex, Apoe4 And Alzheimer’S Disease: Rethinking Drug Discovery In The Era Of Precision Medicine, Manish D. Paranjpe, Jason K. Wang, Yun Zhou

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 …

How The Field Of Infectious Diseases Can Leverage Digital Strategy And Social Media Use During A Pandemic, Jasmine R. Marcelin, Nicolás Cortés-Penfield, Carlos Del Rio, Angel Desai, Ignacio Echenique, Bruno Granwehr, Folake Lawal, Kevin Kuriakose, Dong Heun Lee, Maricar Malinis, Diandra Ruidera, Javeed Siddiqui, Andrej Spec, Talia H. Swartz

Open Access Publications

Rapid information dissemination is critical in a world changing rapidly due to global threats. Ubiquitous internet access has created new methods of information dissemination that are rapid, far-reaching, and universally accessible. However, inaccuracies may accompany rapid information dissemination, and rigorous evaluation of primary data through various forms of peer review is crucial. In an era in which high-quality information can save lives, it is critical that infectious diseases specialists are well versed in digital strategy to effectively disseminate information to colleagues and the community and diminish voices spreading misinformation. In this study, we review how social media can be used …

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.