Medicine and Health Sciences Commons^™

Effects Of Scapular Angular Deviations On Potential For Rotator Cuff Tendon Mechanical Compression, Rebekah L Lawrence, Laura B Richardson, Hannah L Bilodeau, Dane J Bonath, Daniel J Dahn, Mary-Ann Em, Sanjay Sarkar, Jonathan P Braman, Paula M Ludewig

2020-Current year OA Pubs

BACKGROUND: One proposed mechanism of rotator cuff disease is scapular motion impairments contributing to rotator cuff compression and subsequent degeneration.

PURPOSE: To model the effects of scapular angular deviations on rotator cuff tendon proximity for subacromial and internal mechanical impingement risk during scapular plane abduction.

STUDY DESIGN: Descriptive laboratory study.

METHODS: Three-dimensional bone models were reconstructed from computed tomography scans obtained from 10 asymptomatic subjects and 9 symptomatic subjects with a clinical presentation of impingement syndrome. Models were rotated to average scapular orientations from a healthy dataset at higher (120°) and lower (subject-specific) humeral elevation angles to investigate internal and …

Technical Note: Minimizing Cied Artifacts On A 0.35 T Mri-Linac Using Deep Learning, Austen N Curcuru, Deshan Yang, Hongyu An, Phillip S Cuculich, Clifford G Robinson, H Michael Gach

2020-Current year OA Pubs

BACKGROUND: Artifacts from implantable cardioverter defibrillators (ICDs) are a challenge to magnetic resonance imaging (MRI)-guided radiotherapy (MRgRT).

PURPOSE: This study tested an unsupervised generative adversarial network to mitigate ICD artifacts in balanced steady-state free precession (bSSFP) cine MRIs and improve image quality and tracking performance for MRgRT.

METHODS: Fourteen healthy volunteers (Group A) were scanned on a 0.35 T MRI-Linac with and without an MR conditional ICD taped to their left pectoral to simulate an implanted ICD. bSSFP MRI data from 12 of the volunteers were used to train a CycleGAN model to reduce ICD artifacts. The data from the …

Causal Relationships Between Pain, Medical Treatments, And Knee Osteoarthritis: A Graphical Causal Model To Guide Analyses, Haadiya Cheema, Robert Brophy, Jamie Collins, Charles L Cox, Ali Guermazi, Mahima Kumara, Bruce A Levy, Lindsey Macfarlane, Lisa A Mandl, Robert Marx, Faith Selzer, Kurt Spindler, Jeffrey N Katz, Eleanor J Murray

2020-Current year OA Pubs

OBJECTIVE: Randomized controlled trials (RCTs) are a gold standard for estimating the benefits of clinical interventions, but their decision-making utility can be limited by relatively short follow-up time. Longer-term follow-up of RCT participants is essential to support treatment decisions. However, as time from randomization accrues, loss to follow-up and competing events can introduce biases and require covariate adjustment even for intention-to-treat effects. We describe a process for synthesizing expert knowledge and apply this to long-term follow-up of an RCT of treatments for meniscal tears in patients with knee osteoarthritis (OA).

METHODS: We identified 2 post-randomization events likely to impact accurate …

Comparing Bladder Neck Contracture Rate Between Robotic Intracorporeal And Extracorporeal Neobladder Construction, Rohit Bhatt, Dylan J. Mittauer, Joel M. Vetter, Nimrod S. Barashi, Riley Mcginnis, Kenneth G. Sands, Alexander K. Chow, Eric H. Kim

2020-Current year OA Pubs

Robot-assisted radical cystectomy (RARC) has become more accessible to surgeons worldwide, and descriptions of intracorporeal urinary diversion techniques, such as orthotopic neobladder construction, have increased. In this study, we aim to compare the rate of bladder neck contracture (BNC) formation between RARC and two different urinary diversion techniques. We retrospectively reviewed our institutional database for patients with bladder cancer who underwent RARC with intracorporeal neobladder (ICNB) construction (n = 11) or extracorporeal neobladder (ECNB) construction (n = 11) between 2012 and 2020. BNC was defined by the need for an additional surgical procedure (e.g., dilatation, urethrotomy). Patients who underwent RARC …

Genome And Clonal Hematopoiesis Stability Contrasts With Immune, Cfdna, Mitochondrial, And Telomere Length Changes During Short Duration Spaceflight, J Sebastian Garcia-Medina, Irenaeus Chan, Carlos Cruchaga, Kelly Bolton, Et Al.

2020-Current year OA Pubs

BACKGROUND: The Inspiration4 (I4) mission, the first all-civilian orbital flight mission, investigated the physiological effects of short-duration spaceflight through a multi-omic approach. Despite advances, there remains much to learn about human adaptation to spaceflight's unique challenges, including microgravity, immune system perturbations, and radiation exposure.

METHODS: To provide a detailed genetics analysis of the mission, we collected dried blood spots pre-, during, and post-flight for DNA extraction. Telomere length was measured by quantitative PCR, while whole genome and cfDNA sequencing provided insight into genomic stability and immune adaptations. A robust bioinformatic pipeline was used for data analysis, including variant calling to …

Biomarker-Directed Targeted Therapy Plus Durvalumab In Advanced Non-Small-Cell Lung Cancer: A Phase 2 Umbrella Trial, Benjamin Besse, Daniel Morgensztern, Et Al.

2020-Current year OA Pubs

For patients with non-small-cell lung cancer (NSCLC) tumors without currently targetable molecular alterations, standard-of-care treatment is immunotherapy with anti-PD-(L)1 checkpoint inhibitors, alone or with platinum-doublet therapy. However, not all patients derive durable benefit and resistance to immune checkpoint blockade is common. Understanding mechanisms of resistance-which can include defects in DNA damage response and repair pathways, alterations or functional mutations in STK11/LKB1, alterations in antigen-presentation pathways, and immunosuppressive cellular subsets within the tumor microenvironment-and developing effective therapies to overcome them, remains an unmet need. Here the phase 2 umbrella HUDSON study evaluated rational combination regimens for advanced NSCLC following failure of …

Estrogen-Induced Glial Il-1Β Mediates Extrinsic Retinal Ganglion Cell Vulnerability In Murine Nf1 Optic Glioma, Yunshuo Tang, Jit Chatterjee, Ngan Wagoner, Stephanie Bozeman, David H Gutmann

2020-Current year OA Pubs

Optic pathway gliomas (OPGs) arising in children with neurofibromatosis type 1 (NF1) can cause retinal ganglion cell (RGC) dysfunction and vision loss, which occurs more frequently in girls. While our previous studies demonstrated that estrogen was partly responsible for this sexually dimorphic visual impairment, herein we elucidate the underlying mechanism. In contrast to their male counterparts, female Nf1

On The Psychometric Evaluation Of Cognitive Control Tasks: An Investigation With The Dual Mechanisms Of Cognitive Control (Dmcc) Battery, Jean-Paul Snijder, Rongxiang Tang, Julie M Bugg, Andrew R A Conway, Todd S Braver

2020-Current year OA Pubs

The domain of cognitive control has been a major focus of experimental, neuroscience, and individual differences research. Currently, however, no theory of cognitive control successfully unifies both experimental and individual differences findings. Some perspectives deny that there even exists a unified psychometric cognitive control construct to be measured at all. These shortcomings of the current literature may reflect the fact that current cognitive control paradigms are optimized for the detection of within-subject experimental effects rather than individual differences. In the current study, we examine the psychometric properties of the Dual Mechanisms of Cognitive Control (DMCC) task battery, which was designed …

Il-33 Potentiates Histaminergic Itch, Anna M Trier, Aaron M Ver Heul, Avery Fredman, Victoria Le, Zhen Wang, Kelsey Auyeung, James Meixiong, Paola Lovato, Michael J Holtzman, Fang Wang, Xinzhong Dong, Andrew L Ji, Brian S Kim

2020-Current year OA Pubs

BACKGROUND: Itch is a common symptom that can greatly diminish quality of life. Histamine is a potent endogenous pruritogen, and while antihistamines are often the first-line treatment for itch, in conditions like chronic spontaneous urticaria (CSU), many patients remain symptomatic while receiving maximal doses. Mechanisms that drive resistance to antihistamines are poorly defined.

OBJECTIVES: Signaling of the alarmin cytokine IL-33 in sensory neurons is postulated to drive chronic itch by inducing neuronal sensitization to pruritogens. Thus, we sought to determine if IL-33 can augment histamine-induced (histaminergic) itch.

METHODS: Itch behavior was assessed in response to histamine after IL-33 or saline …

Estimating The Treatment And Prophylactic Economic Value Of New Antimicrobials In Managing Antibiotic Resistance And Serious Infections For Common Pathogens In The Usa: A Population Modelling Study, Jason Gordon, Maria Gheorghe, Cale Harrison, Ryan Miller, James Dennis, Lotte Steuten, Simon Goldenberg, Sumanth Gandra, Amer Al-Taie

2020-Current year OA Pubs

BACKGROUND: Antimicrobial resistance is a growing public health concern. There is a global need to estimate the population-level value of developing new antimicrobials and to ensure the effective use of existing antimicrobials as strategies to counteract antimicrobial resistance. To this aim, population-level value criteria need to be considered alongside conventional value measures.

OBJECTIVE: The objective of this study was to develop a novel modelling approach to estimate the value of new antimicrobials, considering the transmission, diversity and enablement elements of STEDI value.

METHODS: We developed a population-based mathematical model for the assessment of antimicrobial value considering both prophylactic use of …

Cystic And Atrophic Kidneys, Atrophic Pancreas, Arcuate Uterus, And Diabetes Mellitus Associated With Deletion Of Hnf1Β Gene, Rachel L Usala, Alberto Sobrero, Amy Riek, Janet Mcgill, Fumihiko Urano

2020-Current year OA Pubs

No abstract provided.

Associations Between Covid-19 And Putative Markers Of Neuroinflammation: A Diffusion Basis Spectrum Imaging Study, Wei Zhang, Aaron J Gorelik, Qing Wang, Sara A Norton, Tamara Hershey, Arpana Agrawal, Janine D Bijsterbosch, Ryan Bogdan

2020-Current year OA Pubs

COVID-19 remains a significant international public health concern. Yet, the mechanisms through which symptomatology emerges remain poorly understood. While SARS-CoV-2 infection may induce prolonged inflammation within the central nervous system, the evidence primarily stems from limited small-scale case investigations. To address this gap, our study capitalized on longitudinal UK Biobank neuroimaging data acquired prior to and following COVID-19 testing (N = 416 including n = 224 COVID-19 cases; M

Once-Daily Oral Berotralstat For Long-Term Prophylaxis Of Hereditary Angioedema: The Open-Label Extension Of The Apex-2 Randomized Trial, Sorena Kiani-Alikhan, H James Wedner, Et Al.

2020-Current year OA Pubs

BACKGROUND: Berotralstat is a first-line, once-daily oral plasma kallikrein inhibitor approved for prophylaxis of hereditary angioedema (HAE) attacks in patients 12 years or older.

OBJECTIVE: This analysis examined the safety and effectiveness of long-term prophylaxis with berotralstat.

METHODS: APeX-2 was a phase 3, parallel-group, multicenter trial in patients with HAE caused by C1-inhibitor deficiency (NCT03485911). Part 1 was a randomized, double-blind, placebo-controlled evaluation of 150 and 110 mg of berotralstat over 24 weeks. In part 2, berotralstat-treated patients continued the same treatment, and placebo-treated patients were re-randomized to 150 or 110 mg of berotralstat for 24 weeks. In part 3, …

Clinical Variants Paired With Phenotype: A Rich Resource For Brain Gene Curation, Maya Chopra, Virginia Lanzotti, Dustin Baldridge, Christina A Gurnett, Philip R O Payne, Et Al.

2020-Current year OA Pubs

PURPOSE: Clinically ascertained variants are under-utilized in neurodevelopmental disorder research. We established the Brain Gene Registry (BGR) to coregister clinically identified variants in putative brain genes with participant phenotypes. Here, we report 179 genetic variants in the first 179 BGR registrants and analyze the proportion that were novel to ClinVar at the time of entry and those that were absent in other disease databases.

METHODS: From 10 academically affiliated institutions, 179 individuals with 179 variants were enrolled into the BGR. Variants were cross-referenced for previous presence in ClinVar and for presence in 6 other genetic databases.

RESULTS: Of 179 variants …

Interventional Treatment For Acute Iliofemoral Deep Venous Thrombosis, Matthew Tan, Suresh Vedantham, Sriram Narayanan, Kurosh Parsi, Alun H Davies

2020-Current year OA Pubs

No abstract provided.

Does Vibrotactile Stimulation Of The Auricular Vagus Nerve Enhance Working Memory? A Behavioral And Physiological Investigation, Gansheng Tan, Josh Adams, Kara Donovan, Phillip Demarest, Jon T Willie, Peter Brunner, Jenna L Gorlewicz, Eric C Leuthardt

2020-Current year OA Pubs

BACKGROUND: Working memory is essential to a wide range of cognitive functions and activities. Transcutaneous auricular vagus nerve stimulation (taVNS) is a promising method to improve working memory performance. However, the feasibility and scalability of electrical stimulation are constrained by several limitations, such as auricular discomfort and inconsistent electrical contact.

OBJECTIVE: We aimed to develop a novel and practical method, vibrotactile taVNS, to improve working memory. Further, we investigated its effects on arousal, measured by skin conductance and pupil diameter.

METHOD: This study included 20 healthy participants. Behavioral response, skin conductance, and eye tracking data were concurrently recorded while the …

Msg-15: Super-Bioavailability Itraconazole Versus Conventional Itraconazole In The Treatment Of Endemic Mycoses-A Multicenter, Open-Label, Randomized Comparative Trial, Andrej Spec, Et Al.

2020-Current year OA Pubs

BACKGROUND: Invasive fungal disease caused by dimorphic fungi is associated with significant morbidity and mortality. Super-bioavailability itraconazole (SUBA-itra) is a novel antifungal agent with pharmacokinetic advantages over currently available formulations. In this prospective comparative study, we report the outcomes of patients with endemic fungal infections (histoplasmosis, blastomycosis, coccidioidomycosis, and sporotrichosis).

METHODS: This open-label randomized trial evaluated the efficacy, safety, and pharmacokinetics SUBA-itra compared with conventional itraconazole (c-itra) treatment for endemic fungal infections. An independent data review committee determined responses on treatment days 42 and 180.

RESULTS: Eighty-eight patients were enrolled for IFD (SUBA-itra, n = 42; c-itra, n = 46) …

Declining Prevalence Of Trichomonas Vaginalis Diagnosed By Wet Mount In A Cohort Of U.S. Women With And Without Hiv, Elizabeth M Daubert, Jodie Dionne, Jessica Atrio, Andrea K Knittel, Seble G Kassaye, Dominika Seidman, Amanda Long, Susan Brockmann, Igho Ofotokun, Margaret A Fischl, L Stewart Massad, Kathleen M Weber

2020-Current year OA Pubs

No abstract provided.

Gene-Based Association Study Of Rare Variants In Children Of Diverse Ancestries Implicates Tnfrsf21 In The Development Of Allergic Asthma, Selene Clay, Katherine Rivera-Spoljaric, Et Al.

2020-Current year OA Pubs

BACKGROUND: Most genetic studies of asthma and allergy have focused on common variation in individuals primarily of European ancestry. Studying the role of rare variation in quantitative phenotypes and in asthma phenotypes in populations of diverse ancestries can provide additional, important insights into the development of these traits.

OBJECTIVE: We sought to examine the contribution of rare variants to different asthma- or allergy-associated quantitative traits in children with diverse ancestries and explore their role in asthma phenotypes.

METHODS: We examined whole-genome sequencing data from children participants in longitudinal studies of asthma (n = 1035; parent-identified as 67% Black and 25% …

Impact Of Diagnostic Stewardship Interventions In The Collection Process Of Fungal Blood Cultures, Miguel A Chavez, Satish Munigala, Carey-Ann D Burnham, Melanie L Yarbrough, Crystal Squires, Josephine Fox, Heather Gasama, Kevin Hsueh, David K Warren

2020-Current year OA Pubs

We implemented 2 interventions to improve utilization and contamination at our institution: kits to improve appropriate sample collection and an electronic order alert displaying appropriate indications of fungal blood cultures. An electronic order alert when ordering fungal blood cultures was associated with decreased utilization without decrease in positivity rate.

Predictors Of Digital Amputation In Diabetic Patients With Surgically Treated Finger Infections, Ella Gibson, Carrie R Bettlach, Emma Payne, John Daines, Linh Vuong, Corinne Merrill, Ida K Fox, Mitchell A Pet

2020-Current year OA Pubs

BACKGROUND: Diabetes is a well-established risk factor for severe digital infection, and patients are more likely to require digital amputation for adequate source control. This study aims to identify factors predictive of digital amputation compared with preservation in patients with diabetes who present with surgically treated finger infections.

METHODS: Current Procedural Terminology (CPT) and International Classification of Diseases Versions 9 and 10 (ICD-9/10) databases from a single academic medical center were queried to identify patients with type 1 or type 2 diabetes mellitus who underwent surgical treatment in the operating room for treatment of a digital infection from 2010 to …

The Conceptual Definition Of Sarcopenia: Delphi Consensus From The Global Leadership Initiative In Sarcopenia (Glis), Ben Kirk, Ellen F Binder, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Sarcopenia, the age-related loss of muscle mass and strength/function, is an important clinical condition. However, no international consensus on the definition exists.

OBJECTIVE: The Global Leadership Initiative in Sarcopenia (GLIS) aimed to address this by establishing the global conceptual definition of sarcopenia.

DESIGN: The GLIS steering committee was formed in 2019-21 with representatives from all relevant scientific societies worldwide. During this time, the steering committee developed a set of statements on the topic and invited members from these societies to participate in a two-phase International Delphi Study. Between 2022 and 2023, participants ranked their agreement with a set of …

Gene Dosage Of Independent Dynein Arm Motor Preassembly Factors Influences Cilia Assembly In Chlamydomonas Reinhardtii, Gervette M. Penny, Susan K. Dutcher

2020-Current year OA Pubs

Motile cilia assembly utilizes over 800 structural and cytoplasmic proteins. Variants in approximately 58 genes cause primary ciliary dyskinesia (PCD) in humans, including the dynein arm (pre)assembly factor (DNAAF) gene DNAAF4. In humans, outer dynein arms (ODAs) and inner dynein arms (IDAs) fail to assemble motile cilia when DNAAF4 function is disrupted. In Chlamydomonas reinhardtii, a ciliated unicellular alga, the DNAAF4 ortholog is called PF23. The pf23-1 mutant assembles short cilia and lacks IDAs, but partially retains ODAs. The cilia of a new null allele (pf23-4) completely lack ODAs and IDAs and are even shorter than cilia from pf23-1. In …

Clinical Characteristics And Treatment Exposure Of Patients With Marked Treatment-Resistant Unipolar Major Depressive Disorder: A Recover Trial Report, Charles R Conway, Christopher L Kriedt, Et Al.

2020-Current year OA Pubs

BACKGROUND: RECOVER is a randomized sham-controlled trial of vagus nerve stimulation and the largest such trial conducted with a psychiatric neuromodulation intervention.

OBJECTIVE: To describe pre-implantation baseline clinical characteristics and treatment history of patients with unipolar, major depressive disorder (MDD), overall and as a function of exposure to interventional psychiatric treatments (INTs), including electroconvulsive therapy, transcranial magnetic stimulation, and esketamine.

METHODS: Medical, psychiatric, and treatment records were reviewed by study investigators and an independent Study Eligibility Committee prior to study qualification. Clinical characteristics and treatment history (using Antidepressant Treatment History [Short] Form) were compared in those qualified (N = 493) …

Decreased Sarcoplasmic Reticulum Phospholipids In Human Skeletal Muscle Are Associated With Metabolic Syndrome, Samantha E Adamson, Sangeeta Adak, Max C Petersen, Dustin Higgins, Larry D Spears, Rong Mei Zhang, Andrea Cedeno, Alexis Mckee, Aswathi Kumar, Sudhir Singh, Fong-Fu Hsu, Janet B Mcgill, Clay F Semenkovich

2020-Current year OA Pubs

Metabolic syndrome affects more than one in three adults and is associated with increased risk of diabetes, cardiovascular disease, and all-cause mortality. Muscle insulin resistance is a major contributor to the development of the metabolic syndrome. Studies in mice have linked skeletal muscle sarcoplasmic reticulum (SR) phospholipid composition to sarcoplasmic/endoplasmic reticulum Ca

Study Characteristics And Impact Of The "Best Papers" Presented At Assh Annual Meetings Over The Past Decade, Justin A Cline, Joshua T Rogers, Guillermo Marquez, Lindley Wall, Charles A Goldfarb

2020-Current year OA Pubs

PURPOSE: Each year, the American Society for Surgery of the Hand (ASSH) selects several abstracts for podium presentations during a "Best Papers" session. We examined these papers to better understand their characteristics and impact on the field of hand surgery.

METHODS: "Best Papers" from the 2010 to 2020 ASSH Annual Meetings were reviewed. Online databases were searched to find matching publications. Descriptive data were collected from the publications. The Hirsch index value for each corresponding author and the number of citations for each publication were recorded. Descriptive statistics were used to analyze the data.

RESULTS: Fifty-nine "Best Papers" were awarded …

The Card8 Inflammasome Dictates Hiv/Siv Pathogenesis And Disease Progression, Qiankun Wang, Kolin M Clark, Ritudhwaj Tiwari, Nagarajan Raju, Gregory K Tharp, Jeffrey Rogers, R Alan Harris, Muthuswamy Raveendran, Steven E Bosinger, Tricia H Burdo, Guido Silvestri, Liang Shan

2020-Current year OA Pubs

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Quantification Of Surface-Localized And Total Oxytocin Receptor In Myometrial Smooth Muscle Cells, Yingye Fang, Erin L Reinl, Audrey Liu, Trinidi D Prochaska, Manasi Malik, Antonina I Frolova, Sarah K England, Princess I Imoukhuede

2020-Current year OA Pubs

Oxytocin acts through the oxytocin receptor (OXTR) to modulate uterine contractility. We previously identified OXTR genetic variants and showed that, in HEK293T cells, two of the OXTR protein variants localized to the cell surface less than wild-type OXTR. Here, we sought to measure OXTR in the more native human myometrial smooth muscle cell (HMSMC) line on both the cell-surface and across the whole cell, and used CRISPR editing to add an HA tag to the endogenous OXTR gene for anti-HA measurement. Quantitative flow cytometry revealed that these cells possessed 55,000 ± 3200 total OXTRs and 4900 ± 390 cell-surface OXTRs …

Integrin Α9Β1 Deficiency Does Not Impact The Development Of Atherosclerosis In Mice, In-Hyuk Jung, Nathan O Stitziel

2020-Current year OA Pubs

Sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1 (SVEP1) is an extracellular matrix protein that causally promotes cardiovascular disease in humans and mice. However, the receptor mediating the effect of SVEP1 on the development of disease remains unclear. We previously demonstrated that depleting either vascular smooth muscle cell (VSMC)- or myeloid cell-derived integrin α9β1, the first receptor that was identified to interact with SVEP1, did not phenocopy the disease-abrogating effect of depleting SVEP1. Due to its wide expression in tissues and cell types, here we extend this line of investigation to definitively determine if integrin α9β1 …

Rrm3 And Pif1 Division Of Labor During Replication Through Leading And Lagging Strand G-Quadruplex, Mor Varon, Daniel Dovrat, Jonathan Heuzé, Ioannis Tsirkas, Saurabh P Singh, Philippe Pasero, Roberto Galletto, Amir Aharoni

2020-Current year OA Pubs

Members of the conserved Pif1 family of 5'-3' DNA helicases can unwind G4s and mitigate their negative impact on genome stability. In Saccharomyces cerevisiae, two Pif1 family members, Pif1 and Rrm3, contribute to the suppression of genomic instability at diverse regions including telomeres, centromeres and tRNA genes. While Pif1 can resolve lagging strand G4s in vivo, little is known regarding Rrm3 function at G4s and its cooperation with Pif1 for G4 replication. Here, we monitored replication through G4 sequences in real time to show that Rrm3 is essential for efficient replisome progression through G4s located on the leading strand template, …