Digital Commons Network^™

Recessive Col4a2 Mutation Leads To Intellectual Disability, Epilepsy, And Spastic Cerebral Palsy, Somayeh Bakhtiari, Abbas Tafakhori, Sheng Chih Jin, Brandon S. Guida, Elham Alehabib, Saghar Firouzabadi, Kaya Bilguvar, Michael C. Fahey, Hossein Darvish, Michael C. Kruer

Open Access Publications

No abstract provided.

Quantitative Evaluation Of Frequency Domain Measurements In High Density Diffuse Optical Tomography, Guy A. Perkins, Adam T. Eggebrecht, Hamid Dehghani

Open Access Publications

No abstract provided.

Dengue And The Lectin Pathway Of The Complement System, Romchat Kraivong, Nuntaya Punyadee, M Kathryn Liszewski, John P Atkinson, Panisadee Avirutnan

Open Access Publications

Dengue is a mosquito-borne viral disease causing significant health and economic burdens globally. The dengue virus (DENV) comprises four serotypes (DENV1-4). Usually, the primary infection is asymptomatic or causes mild dengue fever (DF), while secondary infections with a different serotype increase the risk of severe dengue disease (dengue hemorrhagic fever, DHF). Complement system activation induces inflammation and tissue injury, contributing to disease pathogenesis. However, in asymptomatic or primary infections, protective immunity largely results from the complement system's lectin pathway (LP), which is activated through foreign glycan recognition. Differences in N-glycans displayed on the DENV envelope membrane influence the lectin pattern …

Activated Microglia Mitigate Aβ-Associated Tau Seeding And Spreading, Maud Gratuze, Yun Chen, Samira Parhizkar, Nimansha Jain, Michael R. Strickland, Javier Remolina Serrano, Marco Colonna, Jason D. Ulrich, David M. Holtzman

Open Access Publications

In Alzheimer's disease (AD) models, AD risk variants in the microglial-expressed TREM2 gene decrease Aβ plaque-associated microgliosis and increase neuritic dystrophy as well as plaque-associated seeding and spreading of tau aggregates. Whether this Aβ-enhanced tau seeding/spreading is due to loss of microglial function or a toxic gain of function in TREM2-deficient microglia is unclear. Depletion of microglia in mice with established brain amyloid has no effect on amyloid but results in less spine and neuronal loss. Microglial repopulation in aged mice improved cognitive and neuronal deficits. In the context of AD pathology, we asked whether microglial removal and repopulation decreased …

Il-7 Immunotherapy In A Nonimmunocompromised Patient With Intractable Fungal Wound Sepsis, Isaiah R. Turnbull, Monty B. Mazer, Mark H. Hoofnagle, John P. Kirby, Jennifer M. Leonard, Carlos Mejia-Chew, Andrej Spec, Jane Blood, Sydney M. Miles, Eric M. Ransom, Robert F. Potter, Joseph P. Gaut, Kenneth E. Remy, Richard S. Hotchkiss

Open Access Publications

A nonimmunocompromised patient developed life-threatening soft tissue infection with

Liver-Specific Deletion Of Mttp Versus Tm6sf2 Reveals Distinct Defects In Stepwise Vldl Assembly, Elizabeth P Newberry, Gregory W Strout, James A J Fitzpatrick, Nicholas O Davidson

Open Access Publications

No abstract provided.

Programmed Cell Death Recruits Macrophages Into The Developing Mouse Cochlea, Vikrant Borse, Tejbeer Kaur, Ashley Hinton, Kevin Ohlemiller, Mark E Warchol

Open Access Publications

Programmed cell death (PCD) plays a critical role in the development and maturation of the cochlea. Significant remodeling occurs among cells of the greater epithelial ridge (GER) of Kölliker's organ, leading to tissue regression and formation of the inner sulcus. In mice, this event normally occurs between postnatal days 5-15 (P5-15) and is regulated by thyroid hormone (T3). During this developmental time period, the cochlea also contains a large population of macrophages. Macrophages are frequently involved in the phagocytic clearance of dead cells, both during development and after injury, but the role of macrophages in the developing cochlea is unknown. …

Ga4gh: International Policies And Standards For Data Sharing Across Genomic Research And Healthcare, Heidi I. Rehm, Malachi Griffith, Obi L. Griffith, Et Al

Open Access Publications

No abstract provided.

Shifting Pathways Of Stimulant Use Among Individuals With Opioid Use Disorder: A Retrospective Analysis Of The Last Thirty Years, Matthew S Ellis, Zachary A Kasper, Stephen Scroggins

Open Access Publications

No abstract provided.

Follow The Metaplasia: Characteristics And Oncogenic Implications Of Metaplasia's Pattern Of Spread Throughout The Stomach, José B Sáenz

Open Access Publications

The human stomach functions as both a digestive and innate immune organ. Its main product, acid, rapidly breaks down ingested products and equally serves as a highly effective microbial filter. The gastric epithelium has evolved mechanisms to appropriately handle the myriad of injurious substances, both exogenous and endogenous, to maintain the epithelial barrier and restore homeostasis. The most significant chronic insult that the stomach must face is

Type Iii Interferons: Emerging Roles In Autoimmunity, Sindhu Manivasagam, Robyn S Klein

Open Access Publications

Type III interferons (IFNs) or the lambda IFNs (IFNLs or IFN-λs) are antimicrobial cytokines that play key roles in immune host defense at endothelial and epithelial barriers. IFNLs signal

Overlapping But Disparate Inflammatory And Immunosuppressive Responses To Sars-Cov-2 And Bacterial Sepsis: An Immunological Time Course Analysis, Tyler J Loftus, Ricardo Ungaro, Marvin Dirain, Philip A Efron, Monty B Mazer, Kenneth E Remy, Richard S Hotchkiss, Luer Zhong, Rhonda Bacher, Petr Starostik, Lyle L Moldawer, Scott C Brakenridge

Open Access Publications

Both severe SARS-CoV-2 infections and bacterial sepsis exhibit an immunological dyscrasia and propensity for secondary infections. The nature of the immunological dyscrasias for these differing etiologies and their time course remain unclear. In this study, thirty hospitalized patients with SARS-CoV-2 infection were compared with ten critically ill patients with bacterial sepsis over 21 days, as well as ten healthy control subjects. Blood was sampled between days 1 and 21 after admission for targeted plasma biomarker analysis, cellular phenotyping, and leukocyte functional analysis

Associations Between Education And Dementia In The Caribbean And The United States: An International Comparison, Jing Li, Jorge J Llibre-Guerra, Amal Harrati, Jordan Weiss, Ivonne Z Jiménez-Velázquez, Daisy Acosta, Juan De Jesús Llibre-Rodriguez, Mao-Mei Liu, William H Dow

Open Access Publications

Introduction: Despite high dementia prevalence in Hispanic populations globally, especially Caribbean Hispanics, no study has comparatively examined the association between education and dementia among Hispanics living in the Caribbean Islands and older adults in the United States.

Methods: We used data on 6107 respondents aged 65 and older in the baseline wave of the population-based and harmonized 10/66 survey from Cuba, the Dominican Republic, and Puerto Rico, collected between 2003 and 2008, and 11,032 respondents aged 65 and older from the U.S.-based Health and Retirement Study data in 2014, a total of 17,139 individuals. We estimated multivariable logistic regression models …

Harnessing The Potential Of Multiomics Studies For Precision Medicine In Infectious Disease, Rebecca A. Ward, Philip A. Mudd, Rachel M. Presti, Andrej Spec, Et Al

Open Access Publications

The field of infectious diseases currently takes a reactive approach and treats infections as they present in patients. Although certain populations are known to be at greater risk of developing infection (eg, immunocompromised), we lack a systems approach to define the true risk of future infection for a patient. Guided by impressive gains in "omics" technologies, future strategies to infectious diseases should take a precision approach to infection through identification of patients at intermediate and high-risk of infection and deploy targeted preventative measures (ie, prophylaxis). The advances of high-throughput immune profiling by multiomics approaches (ie, transcriptomics, epigenomics, metabolomics, proteomics) hold …

Evaluation Of Commercial Rapid Lateral Flow Tests, Alone Or In Combination, For Sars-Cov-2 Antibody Testing, Peter U Fischer, Kerstin Fischer, Kurt C Curtis, Yuefang Huang, Nicole Fetcho, Charles W Goss, Gary J Weil

Open Access Publications

Antibody tests can be tools for detecting current or past severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 [coronavirus disease 2019 (COVID-19)]) infections. Independent test evaluations are needed to document the performance with different sample sets. We evaluated six lateral flow assays (LFAs) and two laboratory-based tests (EUROIMMUN-SARS-CoV-2 ELISA and Abbott-Architect-SARS-CoV-2-IgG). We tested 210 plasma samples from 89 patients diagnosed with acute COVID-19. These samples were collected at different time points after the onset of symptoms. In addition, 80 convalescent plasma samples, and 168 pre-pandemic samples collected from adults in the United States and in Africa were tested. LFA performance varied …

Genome‑Wide Chromatin Accessibility Analyses Provide A Map For Enhancing Optic Nerve Regeneration, Wolfgang Pita-Thomas, Tassia Mangetti Gonçalves, Ajeet Kumar, Guoyan Zhao, Valeria Cavalli

Open Access Publications

No abstract provided.

Defining Surgical Terminology And Risk For Brain Computer Interface Technologies, Eric C Leuthardt, Daniel W Moran, Tim R Mullen

Open Access Publications

With the emergence of numerous brain computer interfaces (BCI), their form factors, and clinical applications the terminology to describe their clinical deployment and the associated risk has been vague. The terms "minimally invasive" or "non-invasive" have been commonly used, but the risk can vary widely based on the form factor and anatomic location. Thus, taken together, there needs to be a terminology that best accommodates the surgical footprint of a BCI and their attendant risks. This work presents a semantic framework that describes the BCI from a procedural standpoint and its attendant clinical risk profile. We propose extending the common …

Data Quality Methods Through Remote Source Data Verification Auditing: Results From The Congenital Cardiac Research Collaborative, Joelle A Pettus, Amy L Pajk, Andrew C Glatz, Christopher J Petit, Bryan H Goldstein, Athar M Qureshi, George T Nicholson, Jeffery J Meadows, Jeffrey D Zampi, Mark A Law, Shabana Shahanavaz, Michael S Kelleman, Courtney M Mccracken, Congenital Cardiac Research Collaborative

Open Access Publications

BACKGROUND: Multicentre research databases can provide insights into healthcare processes to improve outcomes and make practice recommendations for novel approaches. Effective audits can establish a framework for reporting research efforts, ensuring accurate reporting, and spearheading quality improvement. Although a variety of data auditing models and standards exist, barriers to effective auditing including costs, regulatory requirements, travel, and design complexity must be considered.

MATERIALS AND METHODS: The Congenital Cardiac Research Collaborative conducted a virtual data training initiative and remote source data verification audit on a retrospective multicentre dataset. CCRC investigators across nine institutions were trained to extract and enter data into …

The Role Of B Cells In Primary Progressive Multiple Sclerosis, Jameson P Holloman, Robert C Axtell, Nancy L Monson, Gregory F Wu

Open Access Publications

The success of ocrelizumab in reducing confirmed disability accumulation in primary progressive multiple sclerosis (PPMS) via CD20-targeted depletion implicates B cells as causal agents in the pathogenesis of PPMS. This review explores the possible mechanisms by which B cells contribute to disease progression in PPMS, specifically exploring cytokine production, antigen presentation, and antibody synthesis. B cells may contribute to disease progression in PPMS through cytokine production, specifically GM-CSF and IL-6, which can drive naïve T-cell differentiation into pro-inflammatory Th1/Th17 cells. B cell production of the cytokine LT-α may induce follicular dendritic cell production of CXCL13 and lead indirectly to T …

Bempedoic Acid For Heterozygous Familial Hypercholesterolemia: From Bench To Bedside, Anandita Agarwala, Renato Quispe, Anne C Goldberg, Erin D Michos

Open Access Publications

Bempedoic acid is a first-in-class, oral, inhibitor of cholesterol biosynthesis that is approved for use in patients with atherosclerotic cardiovascular disease (ASCVD) and for primary prevention in individuals with heterozygous familial hypercholesterolemia (HeFH) by the United States Food and Drug Administration. Pooled data from the phase III clinical trials, CLEAR Harmony and CLEAR Wisdom, have demonstrated the safety and efficacy of bempedoic acid with regard to lowering of low-density lipoprotein cholesterol (LDL-C) in patients with HeFH as an adjunct or alternative to currently existing lipid-lowering therapies. CLEAR Outcomes is a cardiovascular outcomes trial that is currently underway that will provide …

Ron Signalling Promotes Therapeutic Resistance In Esr1 Mutant Breast Cancer, Derek Dustin, Shunqiang Li, Et Al

Open Access Publications

BACKGROUND: Oestrogen Receptor 1 (ESR1) mutations are frequently acquired in oestrogen receptor (ER)-positive metastatic breast cancer (MBC) patients who were treated with aromatase inhibitors (AI) in the metastatic setting. Acquired ESR1 mutations are associated with poor prognosis and there is a lack of effective therapies that selectively target these cancers.

METHODS: We performed a proteomic kinome analysis in ESR1 Y537S mutant cells to identify hyperactivated kinases in ESR1 mutant cells. We validated Recepteur d'Origine Nantais (RON) and PI3K hyperactivity through phospho-immunoblot analysis, organoid growth assays, and in an in vivo patient-derived xenograft (PDX) metastatic model.

RESULTS: We demonstrated that RON …

Transcript Assembly Improves Expression Quantification Of Transposable Elements In Single-Cell Rna-Seq Data, Wanqing Shao, Ting Wang

Open Access Publications

Transposable elements (TEs) are an integral part of the host transcriptome. TE-containing noncoding RNAs (ncRNAs) show considerable tissue specificity and play important roles during development, including stem cell maintenance and cell differentiation. Recent advances in single-cell RNA-seq (scRNA-seq) revolutionized cell type-specific gene expression analysis. However, effective scRNA-seq quantification tools tailored for TEs are lacking, limiting our ability to dissect TE expression dynamics at single-cell resolution. To address this issue, we established a TE expression quantification pipeline that is compatible with scRNA-seq data generated across multiple technology platforms. We constructed TE-containing ncRNA references using bulk RNA-seq data and showed that quantifying …

Humanized Neurofibroma Model From Induced Pluripotent Stem Cells Delineates Tumor Pathogenesis And Developmental Origins, Juan Mo, Corina Anastasaki, Zhiguo Chen, Tracey Shipman, Jason Papke, Kevin Yin, David H Gutmann, Lu Q Le

Open Access Publications

Neurofibromatosis type 1 (NF1) is a common tumor predisposition syndrome caused by NF1 gene mutation, in which affected patients develop Schwann cell lineage peripheral nerve sheath tumors (neurofibromas). To investigate human neurofibroma pathogenesis, we differentiated a series of isogenic, patient-specific NF1-mutant human induced pluripotent stem cells (hiPSCs) into Schwannian lineage cells (SLCs). We found that, although WT and heterozygous NF1-mutant hiPSCs-SLCs did not form tumors following mouse sciatic nerve implantation, NF1-null SLCs formed bona fide neurofibromas with high levels of SOX10 expression. To confirm that SOX10+ SLCs contained the cells of origin for neurofibromas, both Nf1 alleles were inactivated in …

Impact Of New Unos Allocation Criteria On Heart Transplant Practices And Outcomes, Jason Liu, Bin Q. Yang, Akinobu Itoh, Mohammed Faraz Masood, Justin C. Hartupee, Joel D. Schilling

Open Access Publications

No abstract provided.

Evaluation Of Diffusion-Weighted Mri And Geometric Distortion On A 0.35t Mr-Linac At Multiple Gantry Angles, Benjamin Lewis, Anamaria Guta, Stacie Mackey, H Michael Gach, Sasa Mutic, Olga Green, Taeho Kim

Open Access Publications

Diffusion-weighted imaging (DWI) provides a valuable diagnostic tool for tumor evaluation. Yet, it is difficult to acquire daily MRI data sets in the traditional radiotherapy clinical setting due to patient burden and limited resources. However, integrated MRI radiotherapy treatment systems facilitate daily functional MRI acquisitions like DWI during treatment exams. Before ADC values from MR-RT systems can be used clinically their reproducibility and accuracy must be quantified. This study used a NIST traceable DWI phantom to verify ADC values acquired on a 0.35 T MR-LINAC system at multiple gantry angles. A diffusion-weighted echo planar imaging sequence was used for all …

Dairy Intake During Adolescence And Risk Of Colorectal Adenoma Later In Life, Katharina Nimptsch, Yin Cao, Et Al

Open Access Publications

BACKGROUND: Higher dairy intake during adulthood has been associated with lower colorectal cancer risk. As colorectal carcinogenesis spans several decades, we hypothesised that higher dairy intake during adolescence is associated with lower risk of colorectal adenoma, a colorectal cancer precursor.

METHODS: In 27,196 females from the Nurses' Health Study 2, aged 25-42 years at recruitment (1989), who had completed a validated high school diet questionnaire in 1998 and undergone at least one lower bowel endoscopy between 1998 and 2011, logistic regression for clustered data was used to calculate odds ratios (ORs) and 95% confidence intervals (CI).

RESULTS: Colorectal adenomas were …

Tlr3 Controls Constitutive Ifn-Β Antiviral Immunity In Human Fibroblasts And Cortical Neurons, Daxing Gao, Michael S Diamond, Et Al

Open Access Publications

Human herpes simplex virus 1 (HSV-1) encephalitis can be caused by inborn errors of the TLR3 pathway, resulting in impairment of CNS cell-intrinsic antiviral immunity. Deficiencies of the TLR3 pathway impair cell-intrinsic immunity to vesicular stomatitis virus (VSV) and HSV-1 in fibroblasts, and to HSV-1 in cortical but not trigeminal neurons. The underlying molecular mechanism is thought to involve impaired IFN-α/β induction by the TLR3 recognition of dsRNA viral intermediates or by-products. However, we show here that human TLR3 controls constitutive levels of IFNB mRNA and secreted bioactive IFN-β protein, and thereby also controls constitutive mRNA levels for IFN-stimulated genes …

Cd11c+ Cd88+ Cd317+ Myeloid Cells Are Critical Mediators Of Persistent Cns Autoimmunity, Navid Manouchehri, Rehana Z. Hussain, Petra D. Cravens, Ekaterina Esaulova, Maxim N. Artyomov, Brian T. Edelson, Gregory F. Wu, Anne H. Cross, Richard Doelger, Nicolas Loof, Todd N. Eagar, Thomas G. Forsthuber, Laurent Calvier, Joachim Herz, Olaf Stüve

Open Access Publications

No abstract provided.

Monitoring The Variation In The Gut Microbiota Of Captive Woolly Monkeys Related To Changes In Diet During A Reintroduction Process, Camilo Quiroga-González, Luis Alberto Chica Cardenas, Mónica Ramírez, Alejandro Reyes, Camila González, Pablo R. Stevenson

Open Access Publications

No abstract provided.

Recurrence And Coniglobus Volumetric Resolution Of Subacute And Chronic Subdural Hematoma Post-Middle Meningeal Artery Embolization, Ambooj Tiwari, Adam A Dmytriw, Ryan Bo, Nathan Farkas, Phillip Ye, David S Gordon, Karthikeyan M Arcot, David Turkel-Parrella, Jeffrey Farkas

Open Access Publications

OBJECTIVE: To study the efficacy of middle meningeal artery (MMA) embolization for the treatment of chronic subdural hematoma (SDH) and characterize its post-embolization volumetric resolution.

METHODS: Ten patients diagnosed with 13 cSDH underwent MMA embolization. SDH volumes were measured from time of initial discovery on imaging to pre-operative, post-operative, short-term and long-term follow-up. Time between procedure to obliteration was also measured. Volumetric analysis was done using the coniglobus formula, and recurrence rate as well as resolution timeline was defined using best-fit models.

RESULTS: Out of 10 patients, five were recurrent lesions, three were bilateral and seven unilateral cSDH. Average and …