Digital Commons Network^™

Temporal Trends In Incidence Rates Of Lower Extremity Amputation And Associated Risk Factors Among Patients Using Veterans Health Administration Services From 2008 To 2018, Miao Cai, Yan Xie, Benjamin Bowe, Andrew K. Gibson, Mohamed A. Zayed, Tingting Li, Ziyad Al-Aly

Open Access Publications

Importance: Lower extremity amputation (LEA) is associated with significant morbidity and mortality. However, national temporal trends of LEA incidence rates among US veterans and associated factors have not been well characterized.

Objective: To describe the temporal trends of LEA, characterize associated risk factors, and decompose the associations of these risk factors with changes in temporal trends of LEA among US veterans using Department of Veteran Affairs (VA) services between 2008 and 2018.

Design, Setting, and Participants: This cohort study used VA data from 2008 to 2018 to estimate incidence rates of LEA among veterans using VA services. Cox regression models …

Killing The Invaders: Nk Cell Impact In Tumors And Anti-Tumor Therapy, Martina Molgora, Victor S Cortez, Marco Colonna

Open Access Publications

Natural Killer cells belong to group 1 innate lymphoid cells, which also includes ILC1s. NK/ILC1s are highly heterogeneous cell types showing distinct phenotypes across tissues and conditions. NK cells have long been described as innate lymphocytes able to directly and rapidly kill tumor cells without antigen-restriction. Different mechanisms were shown to modulate NK cell activation and tumor resistance, mainly based on cytokine stimulation and receptor-ligand interactions, and several strategies have been developed to target NK cells in tumor immunotherapy to promote NK cell function and overcome tumor evasion. The characterization of ILC1 distinct phenotype and function and the specific role …

Von Willebrand Disease: Proposing Definitions For Future Research, Nathan T. Connell, Jorge Di Paola, Et Al.

Open Access Publications

No abstract provided.

A Cross-Sectional Comparison Of Physical Activity During Covid-19 In A Sample Of Rural And Non-Rural Participants In The Us, Alan M Beck, Amanda S Gilbert, Dixie D Duncan, Eric M Wiedenman

Open Access Publications

Physical activity (PA) pre-COVID-19 was lower in rural areas compared to non-rural areas. The purpose of this study was to determine COVID-19's impact on PA in rural and non-rural residents. A cross-sectional study consisting of a convenience sample of 278 participants (50% rural, 50% non-rural) from 25 states completed an online survey describing their PA behaviors and perceptions during COVID-19. The global physical activity questionnaire was used to determine PA in various domains and summed to determine if the participant met the PA guidelines. Rural participants had a significantly higher body mass index, lower income, and a lower educational attainment. …

Identifying Risk Factors And Patterns For Early Recurrence Of Pancreatic Neuroendocrine Tumors: A Multi-Institutional Study, Charlotte M Heidsma, Ryan Fields, Bradley A Krasnick, Et Al

Open Access Publications

BACKGROUND: Identifying patients at risk for early recurrence (ER) following resection for pancreatic neuroendocrine tumors (pNETs) might help to tailor adjuvant therapies and surveillance intensity in the post-operative setting.

METHODS: Patients undergoing surgical resection for pNETs between 1998-2018 were identified using a multi-institutional database. Using a minimum

RESULTS: Among 807 patients who underwent curative-intent resection for pNETs, the optimal length of RFS to define ER was identified at 18 months (lowest

CONCLUSION: An evidence-based cut-off value for ER after surgery for pNET was defined at 18 months. These data emphasized the importance of close follow-up in the first two years …

Dysfunction Of The Key Ferroptosis-Surveilling Systems Hypersensitizes Mice To Tubular Necrosis During Acute Kidney Injury, Wulf Tonnus, Wenjun Li, Daniel Kreisel, Et Al.

Open Access Publications

No abstract provided.

Mechanical Overstimulation Causes Acute Injury And Synapse Loss Followed By Fast Recovery In Lateral-Line Neuromasts Of Larval Zebrafish, Melanie Holmgren, Michael E. Ravicz, Kenneth E. Hancock, Olga Strelkova, Dorina Kallogjeri, Artur A. Indzhykulian, Mark E. Warchol, Lavinia Sheets

Open Access Publications

Excess noise damages sensory hair cells, resulting in loss of synaptic connections with auditory nerves and, in some cases, hair-cell death. The cellular mechanisms underlying mechanically induced hair-cell damage and subsequent repair are not completely understood. Hair cells in neuromasts of larval zebrafish are structurally and functionally comparable to mammalian hair cells but undergo robust regeneration following ototoxic damage. We therefore developed a model for mechanically induced hair-cell damage in this highly tractable system. Free swimming larvae exposed to strong water wave stimulus for 2 hr displayed mechanical injury to neuromasts, including afferent neurite retraction, damaged hair bundles, and reduced …

Concussion-Reporting Behavior In Rugby: A National Survey Of Rugby Union Players In The United States, J. Chance Miller, Kenneth Shubin Stein, Tyler Moon, David Trofa, Hamish Kerr, Thomas Bottiglieri, C. S. Ahmad

Open Access Publications

Background: Rugby is the fastest growing team sport in the United States for male and female athletes. It is a contact/collision sport with an injury risk profile that includes concussions.

Purpose: To examine the prevalence of concussions in male and female rugby players in the United States and to characterize behaviors around reporting concussions that could be a target for prevention and treatment efforts.

Study Design: Cross-sectional study; Level of evidence, 3.

Methods: An online survey distributed to active members on the USA Rugby membership list was used to examine self-reported concussions in male and female athletes. Concussion-reporting behaviors and …

Inflammatory Pathophysiology As A Contributor To Myeloproliferative Neoplasms, Daniel Arthur Corpuz Fisher, Jared Scott Fowles, Amy Zhou, Stephen Tracy Oh

Open Access Publications

Myeloid neoplasms, including acute myeloid leukemia (AML), myeloproliferative neoplasms (MPNs), and myelodysplastic syndromes (MDS), feature clonal dominance and remodeling of the bone marrow niche in a manner that promotes malignant over non-malignant hematopoiesis. This take-over of hematopoiesis by the malignant clone is hypothesized to include hyperactivation of inflammatory signaling and overproduction of inflammatory cytokines. In the

Tissue Biodistribution And Tumor Targeting Of Near-Infrared Labelled Anti-Cd38 Antibody-Drug Conjugate In Preclinical Multiple Myeloma, Nicholas Cho, Sooah Ko, Monica Shokeen

Open Access Publications

Daratumumab (DARA) is an FDA-approved high-affinity monoclonal antibody targeting CD38 that has shown promising therapeutic efficacy in double refractory multiple myeloma (MM) patients. Despite the well-established clinical efficacy of DARA, not all heavily pretreated patients respond to single-agent DARA, and the majority of patients who initially respond eventually progress. Antibody-drug conjugates (ADCs) combine the highly targeted tumor antigen recognition of antibodies with the cell killing properties of chemotherapy for effective internalization and processing of the drug. In this study, we evaluated the anti-tumor efficacy of DARA conjugated to the maytansine derivative, mertansine (DM1), linked via a non-cleavable bifunctional linker. The …

Metformin Ameliorates The Severity Of Experimental Alport Syndrome, Kohei Omachi, Jeffrey H. Miner, Et Al.

Open Access Publications

No abstract provided.

The Valproate Mediates Radio-Bidirectional Regulation Through Rfwd3-Dependent Ubiquitination On Rad51, Guochao Liu, David Lim, Zuchao Cai, Wenwen Ding, Zhujun Tian, Chao Dong, Fengmei Zhang, Gongshe Guo, Xiaowei Wang, Pingkun Zhou, Zhihui Feng

Open Access Publications

Ionizing radiation (IR) can induce DNA double-strand breaks (DSBs) in tumor cells during radiotherapy (RT), but the efficiency of RT is limited because of the toxicity to normal cells. Locating an adjuvant treatment to alleviate damage in normal cells while sensitizing tumor cells to IR has attracted much attention. Here, using the 7,12-dimethylbenz[α]anthracene (DMBA)-induced malignant transformed MCF10A cells, we found that valproate (VPA), a histone deacetylase inhibitor (HDACi), radiosensitized transformed cells while alleviated IR-induced damage in normal cells at a safe dose (0.5 mM). We further demonstrated the decrease of homologous recombination (HR)-associated Rad51 in the transformed cells was related …

Deep Learning Segmentation Of Triple-Negative Breast Cancer (Tnbc) Patient Derived Tumor Xenograft (Pdx) And Sensitivity Of Radiomic Pipeline To Tumor Probability Boundary, Kaushik Dutta, Sudipta Roy, Timothy Daniel Whitehead, Jingqin Luo, Abhinav Kumar Jha, Shunqiang Li, James Dennis Quirk, Kooresh Isaac Shoghi

Open Access Publications

Preclinical magnetic resonance imaging (MRI) is a critical component in a co-clinical research pipeline. Importantly, segmentation of tumors in MRI is a necessary step in tumor phenotyping and assessment of response to therapy. However, manual segmentation is time-intensive and suffers from inter- and intra- observer variability and lack of reproducibility. This study aimed to develop an automated pipeline for accurate localization and delineation of TNBC PDX tumors from preclinical T1w and T2w MR images using a deep learning (DL) algorithm and to assess the sensitivity of radiomic features to tumor boundaries. We tested five network architectures including U-Net, dense U-Net, …

Photoacoustic Tomography Reconstruction Using Lag-Based Delay Multiply And Sum With A Coherence Factor Improves In Vivo Ovarian Cancer Diagnosis, Guang Yang, Eghbal Amidi, Quing Zhu

Open Access Publications

Ovarian cancer is the fifth most common cause of death due to cancer, and it is the deadliest of all gynecological cancers. Diagnosing ovarian cancer via conventional photoacoustic delay-and-sum beamforming (DAS) presents several challenges, such as poor image resolution and low lesion to background tissue contrast. To address these concerns, we propose an improved beamformer named lag-based delay multiply and sum combined with coherence factor (DMAS-LAG-CF). Simulations and phantom experiments demonstrate that compared with the conventional DAS, the proposed algorithm can provide 1.39 times better resolution and 10.77 dB higher contrast. For patient data, similar performance on contrast ratios has …

Circulating Tumor Cells From Enumeration To Analysis: Current Challenges And Future Opportunities, Yu-Ping Yang, Teresa M Giret, Richard J Cote

Open Access Publications

Circulating tumor cells (CTCs) have been recognized as a major contributor to distant metastasis. Their unique role as metastatic seeds renders them a potential marker in the circulation for early cancer diagnosis and prognosis as well as monitoring of therapeutic response. In the past decade, researchers mainly focused on the development of isolation techniques for improving the recovery rate and purity of CTCs. These developed techniques have significantly increased the detection sensitivity and enumeration accuracy of CTCs. Currently, significant efforts have been made toward comprehensive molecular characterization, ex vivo expansion of CTCs, and understanding the interactions between CTCs and their …

Nasal Septal Perforation Repair With An Inferior Turbinate Flap And Acellular Dermal Matrix, Saeid Mirzai, Andrew H. Lee, John J. Chi

Open Access Publications

Nasal septal perforation is an uncommon disorder that can cause disturbance of nasal physiology. The perforations can vary widely in size, location, and symptomatology. Many different closure techniques have been described in the literature; however, no gold standard has been recognized. The choice of surgical technique usually depends on the characteristics of the perforation and surgeon experience. Due to the goal of perforation repair being restoration of normal nasal physiology, techniques with the best outcomes have been those resurfacing the septum with nasal respiratory mucosa. Here we present our novel surgical method for large (> 2 cm) septal perforation closure …

Phentolamine Mesylate Ophthalmic Solution Provides Lasting Pupil Modulation And Improves Near Visual Acuity In Presbyopic Glaucoma Patients In A Randomized Phase 2b Clinical Trial, Jay S Pepose, Et Al

Open Access Publications

Purpose: Phentolamine mesylate ophthalmic solution (PMOS), applied to the eye topically, was shown previously to have beneficial effects in patients with dim light vision disturbances (DLD), including decreased pupil diameter (PD), improved best-corrected distance visual acuity (BCDVA), as well as lower intraocular pressure (IOP). The ORION-1 trial evaluated the long-term safety and efficacy of PMOS in a glaucomatous, presbyopic population.

Patients and Methods: In this randomized, double-masked, multi-center, placebo-controlled, multiple-dose Phase 2b trial, 39 patients with elevated IOP were randomized to receive one evening dose of study medication or placebo for 14 days. The primary outcome measure was mean change …

Dynamics Of Oddball Sound Processing: Trial-By-Trial Modeling Of Ecog Signals, Françoise Lecaignard, Raphaëlle Bertrand, Peter Brunner, Anne Caclin, Gerwin Schalk, Jérémie Mattout

Open Access Publications

Recent computational models of perception conceptualize auditory oddball responses as signatures of a (Bayesian) learning process, in line with the influential view of the mismatch negativity (MMN) as a prediction error signal. Novel MMN experimental paradigms have put an emphasis on neurophysiological effects of manipulating regularity and predictability in sound sequences. This raises the question of the contextual adaptation of the learning process itself, which on the computational side speaks to the mechanisms of gain-modulated (or precision-weighted) prediction error. In this study using electrocorticographic (ECoG) signals, we manipulated the predictability of oddball sound sequences with two objectives: (i) Uncovering the …

Corynebacterium Species Inhibit Streptococcus Pneumoniae Colonization And Infection Of The Mouse Airway, Kadi J Horn, Alexander C Jaberi Vivar, Vera Arenas, Sameer Andani, Edward N Janoff, Sarah E Clark

Open Access Publications

The stability and composition of the airway microbiome is an important determinant of respiratory health. Some airway bacteria are considered to be beneficial due to their potential to impede the acquisition and persistence of opportunistic bacterial pathogens such as

Assessing The Clinical Requirement Of 2.5% Phenylephrine For Diagnostic Pupil Examination, Junsang Cho, Brent Bruck, James C. Liu, Susan M. Culican

Open Access Publications

No abstract provided.

Green Nanotechnology Of Mgf‑Aunps For Immunomodulatory Intervention In Prostate Cancer Therapy, Menka Khoobchandani, Aslam Khan, Kavita K. Katti, Velaphi C. Thipe, Amal Y. Al-Yasiri, Darsha K. D. Mohandoss, Michael B. Nicholl, Ademar B. Lugão, Chetan P. Hans, Kattesh V. Katti

Open Access Publications

No abstract provided.

Disordered Eating, Food Insecurity, And Weight Status Among Transgender And Gender Nonbinary Youth And Young Adults: A Cross-Sectional Study Using A Nutrition Screening Protocol, Whitney R. Linsenmeyer, Ian M. Katz, Jamie L. Reed, Andrea M. Giedinghagen, Christopher B. Lewis, Sarah K. Garwood

Open Access Publications

No abstract provided.

Native Structure Of The Rhoph Complex, A Key Determinant Of Malaria Parasite Nutrient Acquisition, Chi-Min Ho, Jonathan Jih, Mason Lai, Xiaorun Li, Daniel E. Goldberg, Josh R. Beck, Z. Hong Zhou

Open Access Publications

No abstract provided.

The Utility Of Body Composition Assessment In Nutrition And Clinical Practice: An Overview Of Current Methodology, Clifton J Holmes, Susan B Racette

Open Access Publications

Body composition is a key component for maintaining good general health and longevity. It can be influenced by a variety of factors, including genetics, environment, and lifestyle choices. The assessment of body composition is an essential tool for nutrition specialists to effectively evaluate nutritional status and monitor progression during dietary interventions. As humans age, there is a natural increase in fat mass coupled with a gradual decline in lean mass, specifically in bone and muscle mass. Individuals with a high body fat percentage are at a greater risk of cardiovascular diseases, type 2 diabetes, several types of cancer, and early …

Cancer-Associated Mesothelial Cells Promote Ovarian Cancer Chemoresistance Through Paracrine Osteopontin Signaling, Jin Qian, Bauer L Lesavage, Kelsea M Hubka, Chenkai Ma, Suchitra Natarajan, Joshua T Eggold, Yiren Xiao, Katherine C Fuh, Venkatesh Krishnan, Annika Enejder, Sarah C Heilshorn, Oliver Dorigo, Erinn B Rankin

Open Access Publications

Ovarian cancer is the leading cause of gynecological malignancy-related deaths, due to its widespread intraperitoneal metastases and acquired chemoresistance. Mesothelial cells are an important cellular component of the ovarian cancer microenvironment that promote metastasis. However, their role in chemoresistance is unclear. Here, we investigated whether cancer-associated mesothelial cells promote ovarian cancer chemoresistance and stemness in vitro and in vivo. We found that osteopontin is a key secreted factor that drives mesothelial-mediated ovarian cancer chemoresistance and stemness. Osteopontin is a secreted glycoprotein that is clinically associated with poor prognosis and chemoresistance in ovarian cancer. Mechanistically, ovarian cancer cells induced osteopontin expression …

Mab Das-1 Recognizes 3'-Sulfated Lewis A/C, Which Is Aberrantly Expressed During Metaplastic And Oncogenic Transformation Of Several Gastrointestinal Epithelia, Jeffrey W. Brown, Koushik K. Das, Vasilios Kalas, Kiron M. Das, Jason C. Mills

Open Access Publications

INTRODUCTION: Multiple previous studies have shown the monoclonal antibody Das-1 (formerly called 7E12H12) is specifically reactive towards metaplastic and carcinomatous lesions in multiple organs of the gastrointestinal system (e.g. Barrett's esophagus, intestinal-type metaplasia of the stomach, gastric adenocarcinoma, high-grade pancreatic intraepithelial neoplasm, and pancreatic ductal adenocarcinoma) as well as in other organs (bladder and lung carcinomas). Beyond being a useful biomarker in tissue, mAb Das-1 has recently proven to be more accurate than current paradigms for identifying cysts harboring advanced neoplasia. Though this antibody has been used extensively for clinical, basic science, and translational applications for decades, its epitope has …

Central Vein Sign: A Diagnostic Biomarker In Multiple Sclerosis (Cavs-Ms) Study Protocol For A Prospective Multicenter Trial, D Ontaneda, S Chahin, Et Al

Open Access Publications

The specificity and implementation of current MRI-based diagnostic criteria for multiple sclerosis (MS) are imperfect. Approximately 1 in 5 of individuals diagnosed with MS are eventually determined not to have the disease, with overreliance on MRI findings a major cause of MS misdiagnosis. The central vein sign (CVS), a proposed MRI biomarker for MS lesions, has been extensively studied in numerous cross sectional studies and may increase diagnostic specificity for MS. CVS has desirable analytical, measurement, and scalability properties. "Central Vein Sign: A Diagnostic Biomarker in Multiple Sclerosis (CAVS-MS)" is an NIH-supported, 2-year, prospective, international, multicenter study conducted by the …

The Sarm1 Tir Nadase: Mechanistic Similarities To Bacterial Phage Defense And Toxin-Antitoxin Systems, Aaron Diantonio, Jeffrey Milbrandt, Matthew D Figley

Open Access Publications

The Toll/interleukin-1 receptor (TIR) domain is the signature signalling motif of innate immunity, with essential roles in innate immune signalling in bacteria, plants, and animals. TIR domains canonically function as scaffolds, with stimulus-dependent multimerization generating binding sites for signalling molecules such as kinases and ligases that activate downstream immune mechanisms. Recent studies have dramatically expanded our understanding of the TIR domain, demonstrating that the primordial function of the TIR domain is to metabolize NAD

An International Virtual Hackathon To Build Tools For The Analysis Of Structural Variants Within Species Ranging From Coronaviruses To Vertebrates [Version 2; Peer Review: 1 Approved, 3 Approved With Reservations], Ann M. Mccartney, Daniel Paiva Agustinho, Et Al

Open Access Publications

No abstract provided.

Air Pollution Particulate Matter Amplifies White Matter Vascular Pathology And Demyelination Caused By Hypoperfusion, Mikko T Huuskonen, Qinghai Liu, Krista Lamorie-Foote, Kristina Shkirkova, Michelle Connor, Arati Patel, Axel Montagne, Hans Baertsch, Constantinos Sioutas, Todd E Morgan, Caleb E Finch, Berislav V Zlokovic, William J Mack

Open Access Publications

Cerebrovascular pathologies are commonly associated with dementia. Because air pollution increases arterial disease in humans and rodent models, we hypothesized that air pollution would also contribute to brain vascular dysfunction. We examined the effects of exposing mice to nanoparticulate matter (nPM; aerodynamic diameter ≤200 nm) from urban traffic and interactions with cerebral hypoperfusion. C57BL/6 mice were exposed to filtered air or nPM with and without bilateral carotid artery stenosis (BCAS) and analyzed by multiparametric MRI and histochemistry. Exposure to nPM alone did not alter regional cerebral blood flow (CBF) or blood brain barrier (BBB) integrity. However, nPM worsened the white …