Digital Commons Network^™

Adipose Tissue Hyaluronan Production Improves Systemic Glucose Homeostasis And Primes Adipocytes For Cl 316,243-Stimulated Lipolysis, Yi Zhu, Gordon I. Smith, Samuel Klein, Et Al

Open Access Publications

No abstract provided.

Pge2-Jnk Signaling Axis Non-Canonically Promotes Gli Activation By Protecting Gli2 From Ubiquitin-Proteasomal Degradation, Jun Yang, Weijun Liu, Et Al.

Open Access Publications

No abstract provided.

Mismatch Repair Deficiency Predicts Response To Her2 Blockade In Her2-Negative Breast Cancer, Nindo B. Punturi, Sinem Seker, Vaishnavi Devarakonda, Aloran Mazumder, Rashi Kalra, Ching Hui Chen, Shunqiang Li, Tina Primeau, Matthew J. Ellis, Shyam M. Kavuri, Svasti Haricharan

Open Access Publications

No abstract provided.

Irradiation-Modulated Murine Brain Microenvironment Enhances Gl261-Tumor Growth And Inhibits Anti-Pd-L1 Immunotherapy, Joel R Garbow, Tanner M Johanns, Xia Ge, John A Engelbach, Liya Yuan, Sonika Dahiya, Christina I Tsien, Feng Gao, Keith M Rich, Joseph J H Ackerman

Open Access Publications

Purpose: Clinical evidence suggests radiation induces changes in the brain microenvironment that affect subsequent response to treatment. This study investigates the effect of previous radiation, delivered six weeks prior to orthotopic tumor implantation, on subsequent tumor growth and therapeutic response to anti-PD-L1 therapy in an intracranial mouse model, termed the Radiation Induced Immunosuppressive Microenvironment (RI

Method and Materials: C57Bl/6 mice received focal (hemispheric) single-fraction, 30-Gy radiation using the Leksell GammaKnife

Results: Tumors in previously irradiated brain display aggressive, invasive growth, characterized by viable tumor and large regions of hemorrhage and necrosis. Mice challenged intracranially with GL261 six weeks after prior …

Structure And Function Of Pancreatic Lipase-Related Protein 2 And Its Relationship With Pathological States, Guoying Zhu, Qing Fang, Fengshang Zhu, Dongping Huang, Changqing Yang

Open Access Publications

Pancreatic lipase is critical for the digestion and absorption of dietary fats. The most abundant lipolytic enzymes secreted by the pancreas are pancreatic triglyceride lipase (PTL or PNLIP) and its family members, pancreatic lipase-related protein 1 (PNLIPRP1or PLRP1) and pancreatic lipase-related protein 2 (PNLIPRP2 or PLRP2). Unlike the family's other members, PNLIPRP2 plays an elemental role in lipid digestion, especially for newborns. Therefore, if genetic factors cause gene mutation, or other factors lead to non-expression, it may have an effect on fat digestion and absorption, on the susceptibility to pancreas and intestinal pathogens. In this review, we will summarize what …

Reducing Auditory Nerve Excitability By Acute Antagonism Of Ca2+-Permeable Ampa Receptors, Amit Walia, Choongheon Lee, Jared Hartsock, Shawn S Goodman, Roland Dolle, Alec N Salt, Jeffery T Lichtenhan, Mark A Rutherford

Open Access Publications

Hearing depends on glutamatergic synaptic transmission mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). AMPARs are tetramers, where inclusion of the GluA2 subunit reduces overall channel conductance and Ca

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.

Maturation Of Heterogeneity In Afferent Synapse Ultrastructure In The Mouse Cochlea, Shelby A Payne, Matthew S Joens, Heather Chung, Natalie Skigen, Adam Frank, Sonali Gattani, Kya Vaughn, Allison Schwed, Matt Nester, Atri Bhattacharyya, Guhan Iyer, Bethany Davis, Jason Carlquist, Honey Patel, James A J Fitzpatrick, Mark A Rutherford

Open Access Publications

Auditory nerve fibers (ANFs) innervating the same inner hair cell (IHC) may have identical frequency tuning but different sound response properties. In cat and guinea pig, ANF response properties correlate with afferent synapse morphology and position on the IHC, suggesting a causal structure-function relationship. In mice, this relationship has not been fully characterized. Here we measured the emergence of synaptic morphological heterogeneities during maturation of the C57BL/6J mouse cochlea by comparing postnatal day 17 (p17, ∼3 days after hearing onset) with p34, when the mouse cochlea is mature. Using serial block face scanning electron microscopy and three-dimensional reconstruction we measured …

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

Inhibition Of Discoidin Domain Receptors By Imatinib Prevented Pancreatic Fibrosis Demonstrated In Experimental Chronic Pancreatitis Model, Sapana Bansod, Mohd Aslam Saifi, Chandraiah Godugu

Open Access Publications

No abstract provided.

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.

Assessing The Post‑Treatment Therapeutic Effect Of Pinaverium In Irritable Bowel Syndrome: A Randomized Controlled Trial, Liang Zheng, Qi Xiao, Et Al

Open Access Publications

No abstract provided.

Pediatric Antimicrobial Stewardship Practices At Discharge: A National Survey, Marie E Wang, Kimberly Felder, Jason G Newland, Adam L Hersh, Nipunie S Rajapakse, Zachary I Willis, Ritu Banerjee, Jeffrey S Gerber, Hayden T Schwenk, Louise E Vaz

Open Access Publications

We surveyed pediatric antimicrobial stewardship program (ASP) site leaders within the Sharing Antimicrobial Reports for Pediatric Stewardship collaborative regarding discharge stewardship practices. Among 67 sites, 13 (19%) reported ASP review of discharge antimicrobial prescriptions. These findings highlight discharge stewardship as a potential opportunity for improvement during the hospital-to-home transition.

Multisociety Statement On Coronavirus Disease 2019 (Covid-19) Vaccination As A Condition Of Employment For Healthcare Personnel, David J Weber, Hilary M Babcock, Et Al

Open Access Publications

This consensus statement by the Society for Healthcare Epidemiology of America (SHEA) and the Society for Post-Acute and Long-Term Care Medicine (AMDA), the Association for Professionals in Epidemiology and Infection Control (APIC), the HIV Medicine Association (HIVMA), the Infectious Diseases Society of America (IDSA), the Pediatric Infectious Diseases Society (PIDS), and the Society of Infectious Diseases Pharmacists (SIDP) recommends that coronavirus disease 2019 (COVID-19) vaccination should be a condition of employment for all healthcare personnel in facilities in the United States. Exemptions from this policy apply to those with medical contraindications to all COVID-19 vaccines available in the United States …

Site Selective C–H Functionalization Of Mitragyna Alkaloids Reveals A Molecular Switch For Tuning Opioid Receptor Signaling Efficacy, Srijita Bhowmik, Juraj Galeta, Václav Havel, Melissa Nelson, Abdelfattah Faouzi, Benjamin Bechand, Mike Ansonoff, Tomas Fiala, Amanda Hunkele, Andrew C. Kruegel, John E. Pintar, Susruta Majumdar, Jonathan A. Javitch, Dalibor Sames

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.

Weight And Body Mass Index Change After Switching To Integrase Inhibitors Or Tenofovir Alafenamide Among Women Living With Hiv, Cecile D. Lahiri, Jane O'Halloran, Et Al

Open Access Publications

No abstract provided.

Listeria Exploits Ifitm3 To Suppress Antibacterial Activity In Phagocytes, Joel M. J. Tan, Michael S. Diamond, Et Al

Open Access Publications

No abstract provided.

Multi-Omics Integration Analysis Identifies Novel Genes For Alcoholism With Potential Overlap With Neurodegenerative Diseases, Manav Kapoor, Michael J. Chao, Emma C. Johnson, Gloriia Novikova, Dongbing Lai, Jacquelyn L. Meyers, Jessica Schulman, John I. Nurnberger Jr., Bernice Porjesz, Yunlong Liu, The Collaborative Study On Genetics Of Alcoholism (Coga), Tatiana Foroud, Howard J. Edenberg, Edoardo Marcora, Arpana Agrawal, Alison Goate

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.

Ubib Proteins Regulate Cellular Coq Distribution In Saccharomyces Cerevisiae, Zachary A. Kemmerer, Kyle P. Robinson, Jonathan M. Schmitz, Mateusz Manicki, Brett R. Paulson, Adam Jochem, Paul D. Hutchins, Joshua J. Coon, David J. Pagliarini

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 …

Association Between Smoking And Molecular Subtypes Of Colorectal Cancer, Xiaoliang Wang, Yin Cao, Et Al

Open Access Publications

Background: Smoking is associated with colorectal cancer (CRC) risk. Previous studies suggested this association may be restricted to certain molecular subtypes of CRC, but large-scale comprehensive analysis is lacking.

Methods: A total of 9789 CRC cases and 11 231 controls of European ancestry from 11 observational studies were included. We harmonized smoking variables across studies and derived sex study-specific quartiles of pack-years of smoking for analysis. Four somatic colorectal tumor markers were assessed individually and in combination, including

Results: Heavier smoking was associated with higher risk of CRC overall and stratified by individual markers (

Conclusion: Smoking was associated with …

Cardiac Performance In The First Year Of Age Among Preterm Infants Fed Maternal Breast Milk, Afif El-Khuffash, Adam J. Lewandowski, Amish Jain, Aaron Hamvas, Gautam K. Singh, Philip T. Levy

Open Access Publications

Importance: There is a beneficial association between human breast milk exposure in the neonatal period and cardiac mechanics in adults who were born preterm. It is unknown whether this benefit is apparent in infants in the first year of age.

Objective: To test the hypothesis that higher consumption of mother's own milk in preterm infants is associated with enhanced cardiac performance during the first year of age.

Design, Setting, and Participants: This cross-sectional study of cardiac and nutritional data at an academic medical center included 80 individuals born preterm and 100 individuals in the control group born full-term. All births …