Digital Commons Network^™

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 …

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: …

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 …

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

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 …

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 …

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 …