Digital Commons Network^™

Germline Knockout Of Nr2e3 Protects Photoreceptors In Three Distinct Mouse Models Of Retinal Degeneration, Alexander V Kolesnikov, Daniel P Murphy, Joseph C Corbo, Vladimir J Kefalov

2020-Current year OA Pubs

Retinitis pigmentosa (RP) is a common form of retinal dystrophy that can be caused by mutations in any one of dozens of rod photoreceptor genes. The genetic heterogeneity of RP represents a significant challenge for the development of effective therapies. Here, we present evidence for a potential gene-independent therapeutic strategy based on targeting

Serum Soluble Alpha-Klotho Klotho And Cognitive Functioning In Older Adults Aged 60 And 79: An Analysis Of Cross-Sectional Data Of The National Health And Nutrition Examination Survey 2011 To 2014, Song Ge, Fanghong Dong, Chong Tian, Chih-Hsiang Yang, Minhui Liu, Jingkai Wei

2020-Current year OA Pubs

OBJECTIVES: Klotho, consisting of membrane klotho and soluble alpha-klotho, is found to be associated with better cognitive outcomes in small samples of the aged population. We aimed to examine the association of serum soluble alpha-klotho with cognitive functioning among older adults using a nationally representative sample of U.S. older adults.

METHOD: A total of 2,173 U.S. older adults aged 60-79 years in the National Health and Nutrition Examination Survey from 2011 to 2014 were included in this cross-sectional analysis. Serum soluble alpha-klotho was measured in the laboratory and analyzed with an ELISA kit. Cognitive function was measured using the Consortium …

Guiding Principles For Adolescent Web-Based Portal Access Policies: Interviews With Informatics Administrators, Bryan Sisk, Alison L Antes, Christine Bereitschaft, Madi Enloe, Fabienne Bourgeois, James Dubois

2020-Current year OA Pubs

BACKGROUND: Web-based patient portals are tools that could support adolescents in managing their health and developing autonomy. However, informatics administrators must navigate competing interests when developing portal access policies for adolescents and their parents.

OBJECTIVE: We aimed to assess the perspectives of informatics administrators on guiding principles for the development of web-based health care portal access policies in adolescent health care.

METHODS: We interviewed informatics administrators from US hospitals with ≥50 dedicated pediatric beds. We performed a thematic analysis of guiding principles for developing and implementing adolescent portal access policies.

RESULTS: We interviewed 65 informatics leaders who represented 63 pediatric …

Comprehensive Proteomics Of Csf, Plasma, And Urine Identify Ddc And Other Biomarkers Of Early Parkinson's Disease., Jarod Rutledge, Dan Western, Priyanka Gorijala, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

Parkinson's disease (PD) starts at the molecular and cellular level long before motor symptoms appear, yet there are no early-stage molecular biomarkers for diagnosis, prognosis prediction, or monitoring therapeutic response. This lack of biomarkers greatly impedes patient care and translational research-L-DOPA remains the standard of care more than 50 years after its introduction. Here, we performed a large-scale, multi-tissue, and multi-platform proteomics study to identify new biomarkers for early diagnosis and disease monitoring in PD. We analyzed 4877 cerebrospinal fluid, blood plasma, and urine samples from participants across seven cohorts using three orthogonal proteomics methods: Olink proximity extension assay, SomaScan …

Dark Adaptometry And Optical Coherence Tomography-Angiography In Huntington Disease, Aaditya Shah, Spencer Fuller, Susan Criswell, Rajendra S. Apte

2020-Current year OA Pubs

No abstract provided.

Graduate Medical Education Well-Being Directors In The United States: Who Are They, And What Does The Role Entail?, Larissa R Thomas, Jonathan A Ripp, Jennifer G Duncan

2020-Current year OA Pubs

BACKGROUND: Institutional Graduate Medical Education (GME) Well-being Director (WBD) roles have recently emerged in the United States to support resident and fellow well-being. However, with a standard position description lacking, the current scope and responsibilities of such roles is unknown. This study describes the scope of work, salary support, and opportunities for role definition for those holding institutional leadership positions for GME well-being.

METHODS: In November 2021, 43 members of a national network of GME WBDs in the United States were invited to complete a cross-sectional survey that included questions about job responsibilities, percent effort, and dedicated budget, and a …

Activator Protein Transcription Factors Coordinate Human Il-33 Expression From Noncanonical Promoters In Chronic Airway Disease, Heather E. Raphael, Ghandi F. Hassan, Omar A. Osorio, Lucy S. Cohen, Morgan D. Payne, Ella Katz-Kiriakos, Ishana Tata, Jamie Hicks, Derek E. Byers, Bo Zhang, Jen Alexander-Brett

2020-Current year OA Pubs

IL-33 is a cytokine central to type 2 immune pathology in chronic airway disease. This cytokine is abundantly expressed in the respiratory epithelium and increased in disease, but how expression is regulated is undefined. Here we show that increased IL33 expression occurs from multiple noncanonical promoters in human chronic obstructive pulmonary disease (COPD), and it facilitates production of alternatively spliced isoforms in airway cells. We found that phorbol 12-myristate 13-acetate (PMA) can activate IL33 promoters through protein kinase C in primary airway cells and lines. Transcription factor (TF) binding arrays combined with RNA interference identified activator protein (AP) TFs as …

An Mhealth Intervention To Address Depression And Improve Antiretroviral Therapy Adherence Among Youths Living With Hiv In Uganda: Protocol For A Pilot Randomized Controlled Trial, Proscovia Nabunya, Patricia Cavazos-Rehg, James Mugisha, Erin Kasson, Olive Imelda Namuyaba, Claire Najjuuko, Edward Nsubuga, Lindsey M Filiatreau, Abel Mwebembezi, Fred M Ssewamala

2020-Current year OA Pubs

BACKGROUND: People living with HIV often struggle with mental health comorbidities that lower their antiretroviral therapy (ART) adherence. There is growing evidence that depression treatment may improve ART adherence and result in improved HIV outcomes. Given that mental health services are severely underequipped in low-resource settings, including in Uganda, new solutions to increase access to mental health care and close the treatment gap are urgently needed. This protocol paper presents the Suubi-Mhealth study, which proposed to develop a mobile health (mHealth) intervention for use among Ugandan youths (14-17 years) with comorbid HIV and depression, taking into account their unique contextual, …

Radiological Outcomes Of Magnetically Controlled Growing Rods For The Treatment Of Children With Various Etiologies Of Early-Onset Scoliosis-A Multicenter Study, Pawel Grabala, Munish C Gupta, Daniel E Pereira, Michal Latalski, Anna Danielewicz, Pawel Glowka, Michal Grabala

2020-Current year OA Pubs

No abstract provided.

How Does Weight Gain Since The Age Of 18 Years Affect Breast Cancer Risk In Later Life? A Meta-Analysis, Yunan Han, Ebunoluwa E Otegbeye, Carrie Stoll, Angela Hardi, Graham A Colditz, Adetunji T Toriola

2020-Current year OA Pubs

Early life factors are important risk factors for breast cancer. The association between weight gain after age 18 and breast cancer risk is inconsistent across previous epidemiologic studies. To evaluate this association, we conducted a meta-analysis according to PRISMA guidelines and the established inclusion criteria. We performed a comprehensive literature search using Medline (Ovid), Embase, Scopus, Cochrane Library, and ClinicalTrials.gov to identify relevant studies published before June 3, 2022. Two reviewers independently reviewed the articles for final inclusion. Seventeen out of 4,725 unique studies met the selection criteria. The quality of studies was assessed using the Newcastle-Ottawa Scale (NOS), and …

Successful Suture-Free Repair Of Left Ventricular Rupture Using The Evarrest Patch, Paighton C Miller, Linda J Schulte, Kunal Kotkar

2020-Current year OA Pubs

Left ventricular free wall rupture is a lethal complication of myocardial infarction. Although emergent surgical repair is the treatment of choice, the method of repair remains highly individualized. This report presents a case of spontaneous coronary artery dissection in a patient with Turner syndrome that led to left ventricular free wall rupture and was successfully repaired on cardiopulmonary bypass using a suture-free technique with the EVARREST Fibrin Sealant Patch.

Social Determinants Of Health And Treatment Center Affiliation: Analysis From The Sickle Cell Disease Implementation Consortium Registry, Gustavo G Mendez, Oladipo Cole, Allison A King, Et Al.

2020-Current year OA Pubs

BACKGROUND: Adults with sickle cell disease (SCD) suffer early mortality and high morbidity. Many are not affiliated with SCD centers, defined as no ambulatory visit with a SCD specialist in 2 years. Negative social determinants of health (SDOH) can impair access to care.

HYPOTHESIS: Negative SDOH are more likely to be experienced by unaffiliated adults than adults who regularly receive expert SCD care.

METHODS: Cross-sectional analysis of the SCD Implementation Consortium (SCDIC) Registry, a convenience sample at 8 academic SCD centers in 2017-2019. A Distressed Communities Index (DCI) score was assigned to each registry member's zip code. Insurance status and …

The Importance Of Community Resources For Breastfeeding, Jennifer Locasale-Crouch, Margaret Kathleen Wallace, Timothy Heeren, Stephen Kerr, Yitong Yue, Genevieve Deeken, Khara Turnbull, Brianna Jaworski, Mayaris Cubides Mateus, Rachel Moon, Fern Robin Hauck, Ann Kellams, Eve Colson, Michael Jay Corwin

2020-Current year OA Pubs

BACKGROUND: Breastfeeding has long-lasting effects on children's cognition, behavioral, mental and physical health. Previous research shows parental characteristics (e.g., education, race/ethnicity, income level) are associated with breastfeeding initiation and duration. Further, research shows significant variation in access to community resources by race/ethnicity. It is unclear how community resources may impact breastfeeding practices and how this might intersect with maternal race/ethnicity.

METHODS: This study combined nationally-representative data from the Study of Attitudes and Factors Effecting Infant Care (SAFE), which surveyed US mothers immediately after the infant's birth and at two to six months of infant age, with the Child Opportunity Index …

Dynamic Contrast Optical Coherence Tomography (Dyc-Oct) For Label-Free Live Cell Imaging, Chao Ren, Senyue Hao, Fei Wang, Abigail Matt, Marcello Magri Amaral, Daniel Yang, Leyao Wang, Chao Zhou

2020-Current year OA Pubs

Dynamic contrast optical coherence tomography (DyC-OCT), an emerging imaging method, utilizes fluctuation patterns in OCT signals to enhance contrast, thereby enabling non-invasive label-free volumetric live cell imaging. In this mini review, we explain the core concepts behind DyC-OCT image formation and its system configurations, serving as practical guidance for future DyC-OCT users. Subsequently, we explore its applications in delivering high-quality, contrast-enhanced images of cellular morphology, as well as in monitoring changes in cellular activity/viability assay experiments.

Dual Membrane-Spanning Anti-Sigma Factors Regulate Vesiculation In Bacteroides Thetaiotaomicron, Evan J Pardue, Mariana G Sartorio, Biswanath Jana, Nichollas E Scott, Wandy L Beatty, Juan C Ortiz-Marquez, Tim Van Opijnen, Fong-Fu Hsu, Robert F Potter, Mario F Feldman

2020-Current year OA Pubs

Bacteroidota are abundant members of the human gut microbiota that shape the enteric landscape by modulating host immunity and degrading dietary- and host-derived glycans. These processes are mediated in part by

Differences In The Link Between Social Trait Judgment And Socio-Emotional Experience In Neurotypical And Autistic Individuals, Shangcheng Zhao, Runnan Cao, Chujun Lin, Shuo Wang, Hongbo Yu

2020-Current year OA Pubs

Neurotypical (NT) individuals and individuals with autism spectrum disorder (ASD) make different judgments of social traits from others' faces; they also exhibit different social emotional responses in social interactions. A common hypothesis is that the differences in face perception in ASD compared with NT is related to distinct social behaviors. To test this hypothesis, we combined a face trait judgment task with a novel interpersonal transgression task that induces measures social emotions and behaviors. ASD and neurotypical participants viewed a large set of naturalistic facial stimuli while judging them on a comprehensive set of social traits (e.g., warm, charismatic, critical). …

Proteomic Associations Of Adverse Outcomes In Human Heart Failure, Marie-Joe Dib, Ahmed Diab, Ali Javaheri, Douglas L Mann, Et Al.

2020-Current year OA Pubs

BACKGROUND: Identifying novel molecular drivers of disease progression in heart failure (HF) is a high-priority goal that may provide new therapeutic targets to improve patient outcomes. The authors investigated the relationship between plasma proteins and adverse outcomes in HF and their putative causal role using Mendelian randomization.

METHODS AND RESULTS: The authors measured 4776 plasma proteins among 1964 participants with HF with a reduced left ventricular ejection fraction enrolled in PHFS (Penn Heart Failure Study). Assessed were the observational relationship between plasma proteins and (1) all-cause death or (2) death or HF-related hospital admission (DHFA). The authors replicated nominally significant …

Associations Of Geographic-Based Socioeconomic Factors And Hpv Vaccination Among Male And Female Children In Five Us States, Serena Xiong, Sarah Humble, Alan Barnette, Heather Brandt, Vetta Thompson, Lisa M Klesges, Michelle I Silver

2020-Current year OA Pubs

BACKGROUND: We assessed whether five geographic-based socioeconomic factors (medically underserved area (MUA); healthcare provider shortage area (HPSA); persistent poverty; persistent child poverty; and social vulnerability index (SVI)) were associated with the odds of HPV vaccination initiation, series completion, and parental vaccine hesitancy, and whether the observed relationships varied by gender of the child.

METHODS: An online panel service, administered through Qualtrics®, was used to recruit parents of adolescents 9-17 years of age to complete a one-time survey in 2021. Coverage of the panel included five US states: Arkansas, Mississippi, Missouri, Tennessee, and Southern Illinois. Generalized estimating equation (GEE) models were …

Microglia At Sites Of Atrophy Restrict The Progression Of Retinal Degeneration Via Galectin-3 And Trem2, Chen Yu, Yun Chen, Jinchao Hou, Marco Colonna, Et Al.

2020-Current year OA Pubs

Outer retinal degenerations, including age-related macular degeneration (AMD), are characterized by photoreceptor and retinal pigment epithelium (RPE) atrophy. In these blinding diseases, macrophages accumulate at atrophic sites, but their ontogeny and niche specialization remain poorly understood, especially in humans. We uncovered a unique profile of microglia, marked by galectin-3 upregulation, at atrophic sites in mouse models of retinal degeneration and human AMD. In disease models, conditional deletion of galectin-3 in microglia led to phagocytosis defects and consequent augmented photoreceptor death, RPE damage, and vision loss, indicating protective roles. Mechanistically, Trem2 signaling orchestrated microglial migration to atrophic sites and induced galectin-3 …

Inositol Phosphatase Inpp4b Sustains Ilc1s And Intratumoral Nk Cells Through An Akt-Driven Pathway, Vincent Peng, Tihana Trsan, Raki Sudan, Bishan Bhattarai, Victor S Cortez, Martina Molgora, Jean Vacher, Marco Colonna

2020-Current year OA Pubs

Innate lymphoid cells (ILCs) are a heterogeneous population of lymphocytes that coordinate early immune responses and maintain tissue homeostasis. Type 1 innate immune responses are mediated by natural killer (NK) cells and group 1 ILCs (ILC1s). Despite their shared features, NK cells and ILC1s display profound differences among various tissue microenvironments. Here, we identify the inositol polyphosphatase INPP4B as a hallmark feature of tissue-resident ILC1s and intratumoral NK cells using an scRNA-seq atlas of tissue-associated and circulating NK/ILC1s. Conditional deletion of Inpp4b in ILC1s and NK cells reveals that it is necessary for the homeostasis of tissue-resident ILC1s but not …

The Genetic Basis Of Hydrocephalus: Genes, Pathways, Mechanisms, And Global Impact, Andrew T Hale, Jennifer M Strahle, Et Al.

2020-Current year OA Pubs

Hydrocephalus (HC) is a heterogenous disease characterized by alterations in cerebrospinal fluid (CSF) dynamics that may cause increased intracranial pressure. HC is a component of a wide array of genetic syndromes as well as a secondary consequence of brain injury (intraventricular hemorrhage (IVH), infection, etc.) that can present across the age spectrum, highlighting the phenotypic heterogeneity of the disease. Surgical treatments include ventricular shunting and endoscopic third ventriculostomy with or without choroid plexus cauterization, both of which are prone to failure, and no effective pharmacologic treatments for HC have been developed. Thus, there is an urgent need to understand the …

Reports Of Covid-19 Vaccine Adverse Events In Predominantly Republican Vs Democratic States, David A Asch, Chongliang Luo, Yong Chen

2020-Current year OA Pubs

IMPORTANCE: Antivaccine sentiment is increasingly associated with conservative political positions. Republican-inclined states exhibit lower COVID-19 vaccination rates, but the association between political inclination and reported vaccine adverse events (AEs) is unexplored.

OBJECTIVE: To assess whether there is an association between state political inclination and the reporting rates of COVID-19 vaccine AEs.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used the AE reports after COVID-19 vaccination from the Vaccine Adverse Event Reporting System (VAERS) database from 2020 to 2022, with reports after influenza vaccines from 2019 to 2022 used as a reference. These reports were examined against state-level percentage of Republican …

Survival In Patients With De Novo Metastatic Prostate Cancer, Martin W Schoen, R Bruce Montgomery, Lukas Owens, Saira Khan, Kristen M Sanfilippo, Ruth B Etzioni

2020-Current year OA Pubs

No abstract provided.

A Tunable Flat Terahertz Lens Using Dirac Semimetals: A Simulation Study, P Panahianfar, B Rezaei, A Darafsheh

2020-Current year OA Pubs

We propose and design a flat and tunable terahertz lens achieved through a two-dimensional photonic crystal composed of an array of rods made of a Dirac semimetal placed in air as the background medium. The structure of interest is a graded index photonic crystal, made possible by the slight variations in the rods' radii in a direction perpendicular to the direction of the light propagation. Dirac semimetals' ability to respond to variations in their Fermi energy level manifested as a change in the refractive index provides the tunability of our proposed lens. The interaction of electromagnetic waves with the designed …

A Greb1-Steroid Receptor Feedforward Mechanism Governs Differential Greb1 Action In Endometrial Function And Endometriosis, Sangappa B Chadchan, Eryk Andreas, Stephanie J Gunderson, Patricia T Jimenez, Emily S Jungheim, Kelle H Moley, Et Al.

2020-Current year OA Pubs

Cellular responses to the steroid hormones, estrogen (E2), and progesterone (P4) are governed by their cognate receptor's transcriptional output. However, the feed-forward mechanisms that shape cell-type-specific transcriptional fulcrums for steroid receptors are unidentified. Herein, we found that a common feed-forward mechanism between GREB1 and steroid receptors regulates the differential effect of GREB1 on steroid hormones in a physiological or pathological context. In physiological (receptive) endometrium, GREB1 controls P4-responses in uterine stroma, affecting endometrial receptivity and decidualization, while not affecting E2-mediated epithelial proliferation. Of mechanism, progesterone-induced GREB1 physically interacts with the progesterone receptor, acting as a cofactor in a positive feedback …

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 …

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

A Pragmatic Trial Of A Family-Centered Approach To Childhood Obesity Treatment: Rationale And Study Design, Amanda E Staiano, Alyssa M Button, Alison Baker, Robbie Beyl, Anne-Marie Conn, Angela Lima, Jeanne Lindros, Robert L Newton Jr, Richard I Stein, R Robinson Welch, Stephen Cook, Denise E Wilfley, Team Up Research Group

2020-Current year OA Pubs

BACKGROUND: Family-based behavioral treatment (FBT) is an effective intensive health behavior and lifestyle treatment for obesity reduction in children and adolescents, but families have limited access. The purpose of this randomized, pragmatic, comparative effectiveness trial was to examine changes in child relative weight in a 12-month, enhanced standard of care (eSOC) intervention combined with FBT (eSOC+FBT) vs. eSOC alone.

METHODS: Children aged 6 to 15 years with obesity, and their primary caregiver, were recruited from primary care clinics. Families were randomized 1:1 to eSOC, a staged approach led by the primary care provider that gradually intensified dependent on a child's …

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 …

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 …