Digital Commons Network^™

A Drosophila Heart Optical Coherence Microscopy Dataset For Automatic Video Segmentation, Matthew Fishman, Abigail Matt, Fei Wang, Elena Gracheva, Jiantao Zhu, Xiangping Ouyang, Andrey Komarov, Yuxuan Wang, Hongwu Liang, Chao Zhou

2020-Current year OA Pubs

The heart of the fruit fly, Drosophila melanogaster, is a particularly suitable model for cardiac studies. Optical coherence microscopy (OCM) captures in vivo cross-sectional videos of the beating Drosophila heart for cardiac function quantification. To analyze those large-size multi-frame OCM recordings, human labelling has been employed, leading to low efficiency and poor reproducibility. Here, we introduce a robust and accurate automated Drosophila heart segmentation algorithm, called FlyNet 2.0+, which utilizes a long short-term memory (LSTM) convolutional neural network to leverage time series information in the videos, ensuring consistent, high-quality segmentation. We present a dataset of 213 Drosophila heart videos, equivalent …

Dna Methylation-Mediated Rbpjk Suppression Protects Against Fracture Nonunion Caused By Systemic Inflammation, Ding Xiao, Liang Fang, Zhongting Liu, Yonghua He, Jun Ying, Haocheng Qin, Aiwu Lu, Meng Shi, Tiandao Li, Bo Zhang, Jianjun Guan, Cuicui Wang, Yousef Abu-Amer, Jie Shen

2020-Current year OA Pubs

Challenging skeletal repairs are frequently seen in patients experiencing systemic inflammation. To tackle the complexity and heterogeneity of the skeletal repair process, we performed single-cell RNA sequencing and revealed that progenitor cells were one of the major lineages responsive to elevated inflammation and this response adversely affected progenitor differentiation by upregulation of Rbpjk in fracture nonunion. We then validated the interplay between inflammation (via constitutive activation of Ikk2, Ikk2ca) and Rbpjk specifically in progenitors by using genetic animal models. Focusing on epigenetic regulation, we identified Rbpjk as a direct target of Dnmt3b. Mechanistically, inflammation decreased Dnmt3b expression in progenitor cells, …

State Public Assistance Spending And Survival Among Adults With Cancer, Justin M Barnes, Kenton J Johnston, Kimberly J Johnson, Fumiko Chino, Nosayaba Osazuwa-Peters

2020-Current year OA Pubs

IMPORTANCE: Social determinants of health contribute to disparities in cancer outcomes. State public assistance spending, including Medicaid and cash assistance programs for socioeconomically disadvantaged individuals, may improve access to care; address barriers, such as food and housing insecurity; and lead to improved cancer outcomes for marginalized populations.

OBJECTIVE: To determine whether state-level public assistance spending is associated with overall survival (OS) among individuals with cancer, overall and by race and ethnicity.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included US adults aged at least 18 years with a new cancer diagnosis from 2007 to 2013, with follow-up through 2019. Data …

The Emerging Importance Of Lymphatics In Health And Disease: An Nih Workshop Report, Babak J. Mehrara, Andrea J. Radtke, Gwendalyn J. Randolph, Brianna T. Wachter, Patricia Greenwel, Ilsa I. Rovira, Zorina S. Galis, Selen C. Muratoglu

2020-Current year OA Pubs

The lymphatic system (LS) is composed of lymphoid organs and a network of vessels that transport interstitial fluid, antigens, lipids, cholesterol, immune cells, and other materials in the body. Abnormal development or malfunction of the LS has been shown to play a key role in the pathophysiology of many disease states. Thus, improved understanding of the anatomical and molecular characteristics of the LS may provide approaches for disease prevention or treatment. Recent advances harnessing single-cell technologies, clinical imaging, discovery of biomarkers, and computational tools have led to the development of strategies to study the LS. This Review summarizes the outcomes …

Understanding Disruptions In Cancer Care To Reduce Increased Cancer Burden, Kia L Davis, Nicole Ackermann, Lisa M Klesges, Nora Leahy, Callie Walsh-Bailey, Sarah Humble, Bettina Drake, Vetta L Sanders Thompson

2020-Current year OA Pubs

BACKGROUND: This study seeks to understand how and for whom COVID-19 disrupted cancer care to understand the potential for cancer health disparities across the cancer prevention and control continuum.

METHODS: In this cross-sectional study, participants age 30+residing in an 82-county region in Missouri and Illinois completed an online survey from June-August 2020. Descriptive statistics were calculated for all variables separately and by care disruption status. Logistic regression modeling was conducted to determine the correlates of care disruption.

RESULTS: Participants (N=680) reported 21% to 57% of cancer screening or treatment appointments were canceled/postponed from March 2020 through the end of 2020. …

A High-Performance Speech Neuroprosthesis, Francis R Willett, Erin M Kunz, Chaofei Fan, Donald T Avansino, Guy H Wilson, Eun Young Choi, Foram Kamdar, Matthew F Glasser, Leigh R Hochberg, Shaul Druckmann, Krishna V Shenoy, Jaimie M Henderson

2020-Current year OA Pubs

Speech brain-computer interfaces (BCIs) have the potential to restore rapid communication to people with paralysis by decoding neural activity evoked by attempted speech into text

Landscape Of Team-Based Care To Manage Hypertension: Results From Two Surveys In Low/Middle-Income Countries, Oluwabunmi Ogungbe, Mark D Huffman, Et Al.

2020-Current year OA Pubs

OBJECTIVES: Team-based care is essential for improving hypertension outcomes in low-resource settings. We assessed perceptions of country representatives and healthcare workers (HCWs) on team-based hypertension care in low/middle-income countries.

DESIGN: Two cross-sectional surveys.

SETTING: The first survey (Country Profile Survey) was conducted in 17 countries and eight in-country regions: Algeria, Bangladesh, Burundi, Chile, China (Beijing, Henan, Shandong), Cuba, Ethiopia, India (Kerala, Madhya Pradesh, Maharashtra, Punjab, Telangana), Nepal, Nigeria, Philippines, Saint Lucia, Sri Lanka, Thailand, Turkey, Uganda and Vietnam. The second survey (HCW Survey) was conducted in four countries: Bangladesh, China, Ethiopia and Nigeria.

PARTICIPANTS: Using convenience sampling, participants for the …

Brain Abscess And Stroke In Children And Adults With Hereditary Hemorrhagic Telangiectasia: Analysis Of A Large National Claims Database, Andrew J. White, Itay Marmor, Kate M. Peacock, Katelin B. Nickel, Jessica Zavadil, Margaret A. Olsen

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: Hereditary hemorrhagic telangiectasia (HHT) is an inherited disease associated with pathogenic variants in transforming growth factor-β signaling pathway-related genes, resulting in abnormal vascular development in various organs. Brain arteriovenous malformations (AVMs) may lead to intracranial hemorrhage, and brain abscess or ischemic stroke may result from right to left shunting via pulmonary AVMs. We aimed to investigate the risk for these severe complications in both adults and children with HHT.

METHODS: We conducted a case-control study among participants aged 1-64 years in the MarketScan Commercial (2006-2019) and Multistate Medicaid Databases (2011-2019). We identified cases with HHT using

RESULTS: …

Altered Signaling And Desensitization Responses In Pth1r Mutants Associated With Eiken Syndrome, Ignacio Portales-Castillo, Thomas Dean, Ross W Cheloha, Brendan A Creemer, Jean-Pierre Vilardaga, Sofya Savransky, Ashok Khatri, Harald Jüppner, Thomas J Gardella

2020-Current year OA Pubs

The parathyroid hormone receptor type 1 (PTH1R) is a G protein-coupled receptor that plays key roles in regulating calcium homeostasis and skeletal development via binding the ligands, PTH and PTH-related protein (PTHrP), respectively. Eiken syndrome is a rare disease of delayed bone mineralization caused by homozygous PTH1R mutations. Of the three mutations identified so far, R485X, truncates the PTH1R C-terminal tail, while E35K and Y134S alter residues in the receptor's amino-terminal extracellular domain. Here, using a variety of cell-based assays, we show that R485X increases the receptor's basal rate of cAMP signaling and decreases its capacity to recruit β-arrestin2 upon …

Katp Channels Are Necessary For Glucose-Dependent Increases In Amyloid-Β And Alzheimer's Disease-Related Pathology, John Grizzanti, William R. Moritz, Molly Stanley, Emily E. Caesar, Maria S. Remedi, Celeste M. Karch, Colin G. Nichols, David M. Holtzman, Et Al.

2020-Current year OA Pubs

Elevated blood glucose levels, or hyperglycemia, can increase brain excitability and amyloid-β (Aβ) release, offering a mechanistic link between type 2 diabetes and Alzheimer's disease (AD). Since the cellular mechanisms governing this relationship are poorly understood, we explored whether ATP-sensitive potassium (KATP) channels, which couple changes in energy availability with cellular excitability, play a role in AD pathogenesis. First, we demonstrate that KATP channel subunits Kir6.2/KCNJ11 and SUR1/ABCC8 were expressed on excitatory and inhibitory neurons in the human brain, and cortical expression of KCNJ11 and ABCC8 changed with AD pathology in humans and mice. Next, we explored whether eliminating neuronal …

Spike-Phase Coupling Patterns Reveal Laminar Identity In Primate Cortex, Zachary W Davis, Nicholas M Dotson, Tom P Franken, Lyle Muller, John H Reynolds

2020-Current year OA Pubs

The cortical column is one of the fundamental computational circuits in the brain. In order to understand the role neurons in different layers of this circuit play in cortical function it is necessary to identify the boundaries that separate the laminar compartments. While histological approaches can reveal ground truth they are not a practical means of identifying cortical layers in vivo. The gold standard for identifying laminar compartments in electrophysiological recordings is current-source density (CSD) analysis. However, laminar CSD analysis requires averaging across reliably evoked responses that target the input layer in cortex, which may be difficult to generate in …

The Who Aware (Access, Watch, Reserve) Antibiotic Book And Prevention Of Antimicrobial Resistance, Veronica Zanichelli, Michael Sharland, Bernadette Cappello, Lorenzo Moja, Haileyesus Getahun, Carmem Pessoa-Silva, Hatim Sati, Catharina Van Weezenbeek, Hanan Balkhy, Mariângela Simão, Sumanth Gandra, Benedikt Huttner

2020-Current year OA Pubs

Guidance on the appropriate use of antibiotics for common infections is lacking in many settings. The World Health Organization (WHO) has recently released

Lrp6 High Bone Mass Characterized In Two Generations Harboring A Unique Mutation Of Low-Density Lipoprotein Receptor-Related Protein 6, Michael P Whyte, Steven Mumm, Jonathan C Baker, Fan Zhang, Homer Sedighi, Shenghui Duan, Tim Cundy

2020-Current year OA Pubs

Osteoblast Wnt/

A Trpv4-Dependent Neuroimmune Axis In The Spinal Cord Promotes Neuropathic Pain, Xueming Hu, Lixia Du, Shenbin Liu, Zhou Lan, Kaikai Zang, Jing Feng, Yonghui Zhao, Xingliang Yang, Zili Xie, Peter L. Wang, Aaron M. Ver Heul, Lvyi Chen, Vijay K. Samineni, Yan-Qing Wang, Kory J. Lavine, Robert W. Gereau, Gregory F. Wu, Hongzhen Hu

2020-Current year OA Pubs

Microglia, resident macrophages of the CNS, are essential to brain development, homeostasis, and disease. Microglial activation and proliferation are hallmarks of many CNS diseases, including neuropathic pain. However, molecular mechanisms that govern the spinal neuroimmune axis in the setting of neuropathic pain remain incompletely understood. Here, we show that genetic ablation or pharmacological blockade of transient receptor potential vanilloid type 4 (TRPV4) markedly attenuated neuropathic pain-like behaviors in a mouse model of spared nerve injury. Mechanistically, microglia-expressed TRPV4 mediated microglial activation and proliferation and promoted functional and structural plasticity of excitatory spinal neurons through release of lipocalin-2. Our results suggest …

Building The Foundation For A Community-Generated National Research Blueprint For Inherited Bleeding Disorders: Research Priorities For Mucocutaneous Bleeding Disorders, Robert F Sidonio Jr, Jorge Di Paola, Et Al.

2020-Current year OA Pubs

BACKGROUND: Excessive or abnormal mucocutaneous bleeding (MCB) may impact all aspects of the physical and psychosocial wellbeing of those who live with it (PWMCB). The evidence base for the optimal diagnosis and management of disorders such as inherited platelet disorders, hereditary hemorrhagic telangiectasia (HHT), hypermobility spectrum disorders (HSD), Ehlers-Danlos syndromes (EDS), and von Willebrand disease (VWD) remains thin with enormous potential for targeted research.

RESEARCH DESIGN AND METHODS: National Hemophilia Foundation and American Thrombosis and Hemostasis Network initiated the development of a National Research Blueprint for Inherited Bleeding Disorders with extensive all-stakeholder consultations to identify the priorities of people with …

Skeletal Dysplasia-Causing Trpv4 Mutations Suppress The Hypertrophic Differentiation Of Human Ipsc-Derived Chondrocytes, Amanda R Dicks, Grigory I Maksaev, Zainab Harissa, Alireza Savadipour, Ruhang Tang, Nancy Steward, Wolfgang Liedtke, Colin G Nichols, Chia-Lung Wu, Farshid Guilak

2020-Current year OA Pubs

Mutations in the TRPV4 ion channel can lead to a range of skeletal dysplasias. However, the mechanisms by which TRPV4 mutations lead to distinct disease severity remain unknown. Here, we use CRISPR-Cas9-edited human-induced pluripotent stem cells (hiPSCs) harboring either the mild V620I or lethal T89I mutations to elucidate the differential effects on channel function and chondrogenic differentiation. We found that hiPSC-derived chondrocytes with the V620I mutation exhibited increased basal currents through TRPV4. However, both mutations showed more rapid calcium signaling with a reduced overall magnitude in response to TRPV4 agonist GSK1016790A compared to wildtype (WT). There were no differences in …

Arginine Methylation Of The Pgc-1Α C-Terminus Is Temperature-Dependent, Meryl Mendoza, Mariel Mendoza, Tiffany Lubrino, Sidney Briski, Immaculeta Osuji, Janielle Cuala, Brendan Ly, Ivan Ocegueda, Harvey Peralta, Benjamin A. Garcia, Cecilia I. Zurita-Lopez

2020-Current year OA Pubs

We set out to determine whether the C-terminus (amino acids 481-798) of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α, UniProt Q9UBK2), a regulatory metabolic protein involved in mitochondrial biogenesis, and respiration, is an arginine methyltransferase substrate. Arginine methylation by protein arginine methyltransferases (PRMTs) alters protein function and thus contributes to various cellular processes. In addition to confirming methylation of the C-terminus by PRMT1 as described in the literature, we have identified methylation by another member of the PRMT family, PRMT7. We performed

Substance Use Treatment Utilization Among Women With And Without Human Immunodeficiency Virus, Ayako W Fujita, Aditi Ramakrishnan, Et Al.

2020-Current year OA Pubs

BACKGROUND: Substance use (SU) contributes to poor health outcomes, yet limited data exist to inform strategies to optimize SU treatment among persons with human immunodeficiency virus (HIV). We describe SU and SU treatment utilization among women with and without HIV in the Women's Interagency HIV Study (WIHS).

METHODS: We included data from women enrolled in WIHS from 2013 to 2020. Current SU was self-reported, nonmedical use of drugs in the past year, excluding use of only marijuana. SU treatment utilization was self-reported use of a drug treatment program in the past year. Multivariable regression models were used to investigate associations …

X-Ray And Mr Contrast Bearing Nanoparticles Enhance The Therapeutic Response Of Image-Guided Radiation Therapy For Oral Cancer, Gayatri Sharma, Mir Hadi Razeghi Kondelaji, Guru P. Sharma, Christopher Hansen, Abdul K. Parchur, Shayan Shafiee, Jaidip M. Jagtap, Brian Fish, Carmen Bergom, Eric Paulson, William A. Hall, Heather A. Himburg, Amit Joshi

2020-Current year OA Pubs

INTRODUCTION: Radiation therapy for head and neck squamous cell carcinoma is constrained by radiotoxicity to normal tissue. We demonstrate 100 nm theranostic nanoparticles for image-guided radiation therapy planning and enhancement in rat head and neck squamous cell carcinoma models.

METHODS: PEG conjugated theranostic nanoparticles comprising of Au nanorods coated with Gadolinium oxide layers were tested for radiation therapy enhancement in 2D cultures of OSC-19-GFP-luc cells, and orthotopic tongue xenografts in male immunocompromised Salt sensitive or SS rats via both intratumoral and intravenous delivery. The radiation therapy enhancement mechanism was investigated.

RESULTS: Theranostic nanoparticles demonstrated both X-ray/magnetic resonance contrast in a …

Sting Suppresses Mitochondrial Vdac2 To Govern Rcc Growth Independent Of Innate Immunity, Zhichuan Zhu, Xin Zhou, Hongwei Du, Erica W Cloer, Jiaming Zhang, Liu Mei, Ying Wang, Xianming Tan, Austin J Hepperla, Jeremy M Simon, Jeanette Gowen Cook, Michael B Major, Gianpietro Dotti, Pengda Liu

2020-Current year OA Pubs

STING is an innate immune sensor for immune surveillance of viral/bacterial infection and maintenance of an immune-friendly microenvironment to prevent tumorigenesis. However, if and how STING exerts innate immunity-independent function remains elusive. Here, the authors report that STING expression is increased in renal cell carcinoma (RCC) patients and governs tumor growth through non-canonical innate immune signaling involving mitochondrial ROS maintenance and calcium homeostasis. Mitochondrial voltage-dependent anion channel VDAC2 is identified as a new STING binding partner. STING depletion potentiates VDAC2/GRP75-mediated MERC (mitochondria-ER contact) formation to increase mitochondrial ROS/calcium levels, impairs mitochondria function, and suppresses mTORC1/S6K signaling leading to RCC growth …

Adapting An Intervention To Support Young Caregivers Of Cancer Survivors: A Study Protocol, Janet Njelesani, Melinda S. Kavanaugh, Jean Hunleth

2020-Current year OA Pubs

INTRODUCTION: Of the family members providing care, in the United States over 5.4 million are young people (<18 years of age) and they are the caregivers receiving the least support overall. Given the need to support cancer survivors through a family-centered practice approach, this lack of support and intervention for young caregivers represents a substantial gap in cancer care. In this study, we will adapt a young caregivers intervention, YCare, with young caregivers in families affected by cancer in order to advance support for families in cancer settings. YCare is an intervention that improves the support young caregivers provide through a peer-engaged, multidisciplinary model but has previously not been studied in the cancer care setting.

METHODS: Guided by the updated Consolidated Framework for Implementation Research (CFIR) we will engage stakeholders (i.e., young caregivers, cancer survivors, health care providers) using qualitative (i.e., one-on-one semi-structured interviews) and arts-based methods. Stakeholders will be recruited via cancer registries and community partners. Data will be analyzed descriptively using deductive (e.g., CFIR domains) and inductive (e.g., cancer practice settings) approaches.

DISCUSSION: The results will indicate the critical components for adapting the YCare intervention to the cancer practice context including new intervention elements and …

Open-Source Statistical And Data Processing Tools For Wide-Field Optical Imaging Data In Mice, Lindsey M. Brier, Joseph P. Culver

2020-Current year OA Pubs

SIGNIFICANCE: Wide-field optical imaging (WOI) can produce concurrent hemodynamic and cell-specific calcium recordings across the entire cerebral cortex in animal models. There have been multiple studies using WOI to image mouse models with various environmental or genetic manipulations to understand various diseases. Despite the utility of pursuing mouse WOI alongside human functional magnetic resonance imaging (fMRI), and the multitude of analysis toolboxes in the fMRI literature, there is not an available open-source, user-friendly data processing and statistical analysis toolbox for WOI data.

AIM: To assemble a MATLAB toolbox for processing WOI data, as described and adapted to combine techniques from …

The Evaluation Of The Delayed Swollen Breast In Patients With A History Of Breast Implants, Grace C Keane, Alexandra M Keane, Ryan Diederich, Kaitlyn Kennard, Eric J Duncavage, Terence M Myckatyn

2020-Current year OA Pubs

Breast implants, whether placed for reconstructive or cosmetic purposes, are rarely lifetime devices. Rupture, resulting from compromised implant shell integrity, and capsular contracture caused by constriction of the specialized scar tissue that normally forms around breast implants, have long been recognized, and remain the leading causes of implant failure. It is apparent, however, that women with breast implants may also experience delayed breast swelling due to a range of etiologic factors. While a majority of delayed seromas associated with breast implants have a benign etiology, this presentation cannot be ignored without an adequate workup as malignancies such as breast implant …

Caregiver Perspectives On The Continued Impact Of The Covid-19 Pandemic On Children With Intellectual/Developmental Disabilities, R A Northrup, E Jones, V Singh, C Holingue, M Meck, C A Gurnett, M Van Stone, L G Kalb

2020-Current year OA Pubs

The COVID-19 pandemic has significantly impacted caregivers, especially those raising a child with an intellectual/developmental disability (IDD). While research has shown substantial disruption to the family, school, and occupational lives of the IDD community, little is known about the long-term impacts of COVID-19. To address this question, 249 caregivers were surveyed via an online questionnaire, between April and August of 2022 (more than 2 years into the pandemic) about potential impacts of the COVID-19 pandemic on their child's access to health- and school-based therapeutic services, caregiver mental health, and family life. The majority of caregivers reported disruptions in access to …

Genetics Of Vegetarianism: A Genome-Wide Association Study, Nabeel R. Yaseen, Catriona L. K. Barnes, Lingwei Sun, Akiko Takeda, John P. Rice

2020-Current year OA Pubs

A substantial body of evidence points to the heritability of dietary preferences. While vegetarianism has been practiced for millennia in various societies, its practitioners remain a small minority of people worldwide, and the role of genetics in choosing a vegetarian diet is not well understood. Dietary choices involve an interplay between the physiologic effects of dietary items, their metabolism, and taste perception, all of which are strongly influenced by genetics. In this study, we used a genome-wide association study (GWAS) to identify loci associated with strict vegetarianism in UK Biobank participants. Comparing 5,324 strict vegetarians to 329,455 controls, we identified …