Digital Commons Network^™

Sleep-Disordered Breathing In Pregnancy: A Developmental Origin Of Offspring Obesity?, Sarah S Farabi, Linda A Barbour, Teri L Hernandez

Open Access Publications

Sleep-disordered breathing (SDB) worsens over pregnancy, and obstructive sleep apnea is associated with serious maternal complications. Intrauterine exposures that provoke insulin resistance (IR), inflammation, or oxidative stress may have long-term offspring health consequences. In obesity, worsening maternal SDB appears to be an exposure that increases the risk for both small- or large-for-gestational-age (SGA, LGA, respectively), suggesting distinct outcomes linked to a common maternal phenotype. The aim of this paper is to systematically review and link data from both mechanistic rodent models and descriptive human studies to characterize the impact of maternal SDB on fetal development. A systematic review of the …

An Open Label, Block Randomized, Community Study Of The Safety And Efficacy Of Co-Administered Ivermectin, Diethylcarbamazine Plus Albendazole Vs. Diethylcarbamazine Plus Albendazole For Lymphatic Filariasis In India, Purushothaman Jambulingam, Vijesh Sreedhar Kuttiatt, Kaliannagounder Krishnamoorthy, Swaminathan Subramanian, Adinarayanan Srividya, Hari Kishan K. Raju, Manju Rahi, Roopali K. Somani, Mallanna K. Suryaprakash, Gangeshwar P. Dwivedi, Gary J Weil

Open Access Publications

No abstract provided.

A Two-Hit Model Of Alcoholic Liver Disease That Exhibits Rapid, Severe Fibrosis, Monideepa Sengupta, Suomia Abuirqeba, Amina Kameric, Aurore Cecile-Valfort, Arindam Chatterjee, Kristine Griffett, Thomas P. Burris, Colin A. Flaveny

Open Access Publications

Alcoholic liver disease (ALD) is responsible for an average of 50.4% and 44.2%of liver disease deaths among males and females respectively. Driven by alcohol misuse, ALD is often reversible by cessation of consumption. However, abstinence programs can have limited success at curtailing abuse, and the loss of life. ALD, therefore, remains a significant clinical challenge. There is a need for effective treatments that prevent or reverse alcohol-induced liver damage to complement or supplant behavioral interventions. Metabolic syndrome, which is disproportionally prevalent in ALD patients, accelerates the progression of ALD and increases liver disease mortality. Current rodent models of ALD unfortunately …

Mr-Guided Radiotherapy For Liver Malignancies, Luca Boldrini, Stefanie Corradini, Cihan Gani, Lauren Henke, Ali Hosni, Angela Romano, Laura Dawson

Open Access Publications

MR guided radiotherapy represents one of the most promising recent technological innovations in the field. The possibility to better visualize therapy volumes, coupled with the innovative online adaptive radiotherapy and motion management approaches, paves the way to more efficient treatment delivery and may be translated in better clinical outcomes both in terms of response and reduced toxicity. The aim of this review is to present the existing evidence about MRgRT applications for liver malignancies, discussing the potential clinical advantages and the current pitfalls of this new technology.

Fast Inactivation Of Nav Current In Rat Adrenal Chromaffin Cells Involves Two Independent Inactivation Pathways, Pedro L. Martinez-Espinosa, Alan Neely, Jiuping Ding, Christopher J. Lingle

Open Access Publications

Voltage-dependent sodium (Nav) current in adrenal chromaffin cells (CCs) is rapidly inactivating and tetrodotoxin (TTX)-sensitive. The fractional availability of CC Nav current has been implicated in regulation of action potential (AP) frequency and the occurrence of slow-wave burst firing. Here, through recordings of Nav current in rat CCs, primarily in adrenal medullary slices, we describe unique inactivation properties of CC Nav inactivation that help define AP firing rates in CCs. The key feature of CC Nav current is that recovery from inactivation, even following brief (5 ms) inactivation steps, exhibits two exponential components of similar amplitude. Various paired pulse protocols …

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.

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 …

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 …

Anti-Inflammatory Dopamine- And Serotonin-Based Endocannabinoid Epoxides Reciprocally Regulate Cannabinoid Receptors And The Trpv1 Channel, William R. Arnold, Lauren N. Carnevale, Zili Xie, Javier L. Baylon, Emad Tajkhorshid, Hongzhen Hu, Aditi Das

Open Access Publications

No abstract provided.

Acupuncture And Oxytocinergic System: The Promising Treatment For Autism, Tangfeng Su, Lei Pei

Open Access Publications

No abstract provided.

Tumor-Associated Neutrophils (Tans) In Human Carcinoma-Draining Lymph Nodes: A Novel Tan Compartment, Silvia Lonardi, William Vermi, Et Al.

Open Access Publications

No abstract provided.

Achieving A Diverse, Equitable, And Inclusive Environment For The Black Orthopaedic Surgeon: Part 1: Barriers To Successful Recruitment Of Black Applicants, Gabriella E Ode, Letitia Bradford, William A Ross, Eric W Carson, Jaysson T Brooks

Open Access Publications

No abstract provided.

Sex Differences In Clinical Outcomes Following Surgical Treatment Of Femoroacetabular Impingement, Tristan Maerz, Jeffrey J Nepple, Asheesh Bedi, Ira Zaltz, Étienne Belzile, Paul E Beaulé, Ernest L Sink, John C Clohisy, Anchor Group

Open Access Publications

BACKGROUND: Sex-based differences in clinical outcomes following surgical treatment of femoroacetabular impingement remain largely uncharacterized; this prospective, multicenter study evaluated these differences both directly and adjusted for covariates.

METHODS: Hips undergoing surgical treatment of symptomatic femoroacetabular impingement were prospectively enrolled in a multicenter cohort. Patient demographics, radiographic parameters, intraoperatively assessed disease severity, and history of surgical procedures, as well as patient-reported outcome measures, were collected preoperatively and at a mean follow-up of 4.3 years. A total of 621 (81.6%) of 761 enrolled hips met the minimum 1 year of follow-up and were included in the analysis; 56.7% of analyzed hips …

Pore-Forming Transmembrane Domains Control Ion Selectivity And Selectivity Filter Conformation In The Kirbac1.1 Potassium Channel, Marcos Matamoros, Colin G. Nichols

Open Access Publications

Potassium (K+) channels are membrane proteins with the remarkable ability to very selectively conduct K+ ions across the membrane. High-resolution structures have revealed that dehydrated K+ ions permeate through the narrowest region of the pore, formed by the backbone carbonyls of the signature selectivity filter (SF) sequence TxGYG. However, the existence of nonselective channels with similar SF sequences, as well as effects of mutations in other regions on selectivity, suggest that the SF is not the sole determinant of selectivity. We changed the selectivity of the KirBac1.1 channel by introducing mutations at residue I131 in transmembrane helix 2 (TM2). These …

Task-Generic And Task-Specific Connectivity Modulations In The Adhd Brain: An Integrated Analysis Across Multiple Tasks, Roselyne J. Chauvin, Jan K. Buitelaar, Emma Sprooten, Marianne Oldehinkel, Barbara Franke, Catharina Hartman, Dirk J. Heslenfeld, Pieter J. Hoekstra, Jaap Oosterlaan, Christian F. Beckmann, Maarten Mennes

Open Access Publications

No abstract provided.

Cerebral Expression Of Metabotropic Glutamate Receptor Subtype 5 In Idiopathic Autism Spectrum Disorder And Fragile X Syndrome: A Pilot Study, James Robert Brašić, Ayon Nandi, David S Russell, Danna Jennings, Olivier Barret, Samuel D Martin, Keith Slifer, Thomas Sedlak, John P Seibyl, Dean F Wong, Dejan B Budimirovic

Open Access Publications

Multiple lines of evidence suggest that dysfunction of the metabotropic glutamate receptor subtype 5 (mGluR

White Matter Integrity Of Contralesional And Transcallosal Tracts May Predict Response To Upper Limb Task-Specific Training In Chronic Stroke, Daniela J S Mattos, Jerrel Rutlin, Xin Hong, Kristina Zinn, Joshua S Shimony, Alexandre R Carter

Open Access Publications

OBJECTIVE: To investigate white matter (WM) plasticity induced by intensive upper limb (UL) task specific training (TST) in chronic stroke.

METHODS: Diffusion tensor imaging data and UL function measured by the Action Research Arm Test (ARAT) were collected in 30 individuals with chronic stroke prior to and after intensive TST. ANOVAs tested the effects of training on the entire sample and on the Responders [ΔARAT ≥ 5.8, N = 13] and Non-Responders [ΔARAT < 5.8, N = 17] groups. Baseline fractional anisotropy (FA) values were correlated with ARATpost TST controlling for baseline ARAT and age to identify voxels predictive of response to TST.

RESULTS: While ARAT scores increased following training (p < 0.0001), FA changes within major WM tracts were not significant at p < 0.05. In the Responder group, larger baseline FA of both contralesional (CL) and transcallosal tracts predicted larger ARAT scores post-TST. Subcortical lesions and more severe damage to transcallosal tracts were more pronounced in the Non-Responder than in the Responder group.

CONCLUSIONS: The motor improvements post-TST in the Responder group may reflect the engagement of interhemispheric processes not available to …

Emerging Genotype-Phenotype Relationships In Primary Ciliary Dyskinesia, Steven K Brennan, Thomas W Ferkol, Stephanie D Davis

Open Access Publications

Primary ciliary dyskinesia (PCD) is a rare inherited condition affecting motile cilia and leading to organ laterality defects, recurrent sino-pulmonary infections, bronchiectasis, and severe lung disease. Research over the past twenty years has revealed variability in clinical presentations, ranging from mild to more severe phenotypes. Genotype and phenotype relationships have emerged. The increasing availability of genetic panels for PCD continue to redefine these genotype-phenotype relationships and reveal milder forms of disease that had previously gone unrecognized.

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, …

Advances In Genetic And Molecular Understanding Of Alzheimer's Disease, Laura Ibanez, Carlos Cruchaga, Maria Victoria Fernández

Open Access Publications

Alzheimer's disease (AD) has become a common disease of the elderly for which no cure currently exists. After over 30 years of intensive research, we have gained extensive knowledge of the genetic and molecular factors involved and their interplay in disease. These findings suggest that different subgroups of AD may exist. Not only are we starting to treat autosomal dominant cases differently from sporadic cases, but we could be observing different underlying pathological mechanisms related to the amyloid cascade hypothesis, immune dysfunction, and a tau-dependent pathology. Genetic, molecular, and, more recently, multi-omic evidence support each of these scenarios, which are …

Optical Emission-Based Phantom To Verify Coincidence Of Radiotherapy And Imaging Isocenters On An Mr-Linac, Jacqueline M Andreozzi, Petr Brůža, Jochen Cammin, Daniel A Alexander, Brian W Pogue, Olga Green, David J Gladstone

Open Access Publications

PURPOSE: Demonstrate a novel phantom design using a remote camera imaging method capable of concurrently measuring the position of the x-ray isocenter and the magnetic resonance imaging (MRI) isocenter on an MR-linac.

METHODS: A conical frustum with distinct geometric features was machined out of plastic. The phantom was submerged in a small water tank, and aligned using room lasers on a MRIdian MR-linac (ViewRay Inc., Cleveland, OH). The phantom physical isocenter was visualized in the MR images and related to the DICOM coordinate isocenter. To view the x-ray isocenter, an intensified CMOS camera system (DoseOptics LLC., Hanover, NH) was placed …

Extracorporeal Life Support For Cardiogenic Shock With Either A Percutaneous Ventricular Assist Device Or An Intra-Aortic Balloon Pump, Tomohiro Nakajima, Yuki Tanaka, Irene Fischer, Kunal Kotkar, Ralph J Damiano Jr, Marc R Moon, Muhammad F Masood, Akinobu Itoh

Open Access Publications

Extracorporeal life support (ECLS) can result in complications due to increased left ventricular (LV) afterload. The percutaneous ventricular assist device (PVAD) and intra-aortic balloon pump (IABP) are both considered to be effective means of LV unloading. This study describes the efficacy of LV unloading and related outcomes with PVAD or IABP during ECLS. From January 2010 to April 2018, all cardiogenic shock patients who underwent ECLS plus simultaneous PVAD or IABP were analyzed. Forty-nine patients received ECLS + PVAD, while 91 received ECLS + IABP. At 48 hours, mean pulmonary artery pressure was significantly reduced in both groups [34 mm …

Analysis Of Ureteral Diameter And Peristalsis In Response To Irrigant Fluid Temperature Changes In An In Vivo Porcine Model, Roshan M. Patel, Pengbo Jiang, Rajiv Karani, Tarik Phillips, Raphael B. Arada, Lillian Xie, Hyder Said, Shlomi Tapiero, Jaime Landman, Ted Farzaneh, Ramakrishna Venkatesh, Ralph V. Clayman

Open Access Publications

No abstract provided.

Fluvoxamine: A Review Of Its Mechanism Of Action And Its Role In Covid-19, Vikas P Sukhatme, Angela M Reiersen, Sharat J Vayttaden, Vidula V Sukhatme

Open Access Publications

Fluvoxamine is a well-tolerated, widely available, inexpensive selective serotonin reuptake inhibitor that has been shown in a small, double-blind, placebo-controlled, randomized study to prevent clinical deterioration of patients with mild coronavirus disease 2019 (COVID-19). Fluvoxamine is also an agonist for the sigma-1 receptor, through which it controls inflammation. We review here a body of literature that shows important mechanisms of action of fluvoxamine and other SSRIs that could play a role in COVID-19 treatment. These effects include: reduction in platelet aggregation, decreased mast cell degranulation, interference with endolysosomal viral trafficking, regulation of inositol-requiring enzyme 1α-driven inflammation and increased melatonin levels, …

A Rapid Motor Task-Based Screening Tool For Parkinsonism In Community-Based Studies, Wendy W Dlamini, Searles Nielsen, Mwiza Ushe, Gill Nelson, Brad A Racette

Open Access Publications

No abstract provided.

Label-Free Macroscopic Fluorescence Lifetime Imaging Of Brain Tumors, Maria Lukina, Konstantin Yashin, Elena E Kiseleva, Anna Alekseeva, Varvara Dudenkova, Elena V Zagaynova, Evgenia Bederina, Igor Medyanic, Wolfgang Becker, Deependra Mishra, Mikhail Berezin, Vladislav I Shcheslavskiy, Marina Shirmanova

Open Access Publications

Advanced stage glioma is the most aggressive form of malignant brain tumors with a short survival time. Real-time pathology assisted, or image guided surgical procedures that eliminate tumors promise to improve the clinical outcome and prolong the lives of patients. Our work is focused on the development of a rapid and sensitive assay for intraoperative diagnostics of glioma and identification of optical markers essential for differentiation between tumors and healthy brain tissues. We utilized fluorescence lifetime imaging (FLIM) of endogenous fluorophores related to metabolism of the glioma from freshly excised brains tissues. Macroscopic time-resolved fluorescence images of three intracranial animal …

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

Familial History Of Autoimmune Disorders Among Patients With Pediatric Multiple Sclerosis, Benjamin M. Greenberg, Soe S. Mar, Shannon Liang, Manu Goyal, Et Al

Open Access Publications

No abstract provided.

Machine Learning Model With Physical Constraints For Diffuse Optical Tomography, Yun Zou, Yifeng Zeng, Shuying Li, Quing Zhu

Open Access Publications

No abstract provided.

Work Organization Factors Associated With Health And Work Outcomes Among Apprentice Construction Workers: Comparison Between The Residential And Commercial Sectors, Ann Marie Dale, Diane S Rohlman, Lisa Hayibor, Bradley A Evanoff

Open Access Publications

There are substantial differences in work organization between residential and commercial construction sectors. This paper examined differences in work factors between construction sectors and examined the association between sector and health behaviors, health outcomes, and work outcomes. We surveyed 929 male construction apprentices (44% residential and 56% commercial) and found that residential apprentices reported fewer workplace safety policies, higher frequency of heavy lifting, and greater likelihood of reporting musculoskeletal pain compared to apprentices in commercial work. Residential apprentices reported higher job strain, lower supervisor support, more lost workdays due to pain or injury, and lower productivity related to health than …