Digital Commons Network^™

Medical Ethics Principles Underscore Advocating For Human Papillomavirus Vaccine, C Mary Healy, Lara S Savas, Ross Shegog, Rebecca Lunstroth, Sally W Vernon

Journal Articles

Studies have consistently shown that vaccination rates against human papillomavirus (HPV) lag far behind other adolescent vaccinations recommended at the same age, resulting in exposing adolescents to unnecessary future risk of infection, and genital and head and neck cancers. Studies also have demonstrated that a major barrier to vaccination is lack of a strong provider recommendation. Factors that providers offer for failing to give a strong recommendation range from perception that the child is not at risk or the need to explain that the vaccine is not mandated (lack of equity and justice) or respect for parental autonomy. We look …

Fruit And Vegetable Shopping Behavior And Intake Among Low-Income Minority Households With Elementary-Aged Children, Brittni N Metoyer, Ru-Jye Chuang, Minjae Lee, Christine Markham, Eric Brown, Maha Almohamad, Jayna M Dave, Shreela V Sharma

Journal Articles

Low-income children and families do not meet the recommendations for fruit and vegetable (FV) intake. This study aimed to assess the association between FV shopping behavior and child FV intake through a cross-sectional study design analyzing self-reported surveys (n = 6074) from adult-child dyads of Hispanic/Latino and African American participants enrolled in the Brighter Bites co-op program. Through quantitative mixed effects linear regression models, accounting for school-level clustering and adjusting for covariates, child FV intake was positively associated with shopping for FV at large chain grocery stores (p < 0.001), natural/organic supermarkets (p < 0.001), warehouse club stores (p = 0.002), discount superstores (p < 0.001), small local stores/corner stores (p = 0.038), convenience stores (p = 0.022), ethnic markets (p = 0.002), farmers’ markets/co-op/school farm stands (p < 0.001), and gardens (p = 0.009) among Hispanic/Latinos participants. Among African American participants, there was significant positive association between child FV intake and shopping for FV at natural/organic supermarkets (p < 0.001), discount superstores (p = 0.005), and convenience stores (p = 0.031). The relationship between location and frequency of shopping for FV and child FV intake varied between races. Further research is needed to better understand the influence of cultural and physical environmental factors. Nutrition education programs are vital to encouraging families to make healthier food choices and purchases to improve child FV consumption.

Intestinal Iga-Coated Bacteria In Healthy- And Altered-Microbiomes (Dysbiosis) And Predictive Value In Successful Fecal Microbiota Transplantation, Herbert L Dupont, Zhi-Dong Jiang, Ashley S Alexander, Andrew W Dupont, Eric L Brown

Journal Articles

IgA-coated bacteria in the gut (IgA-biome) provide a homeostatic function in healthy people through inhibition of microbial invaders and by protecting the epithelial monolayer of the gut. The laboratory methods used to detect this group of bacteria require flow cytometry and DNA sequencing (IgA-Seq). With dysbiosis (reduced diversity of the microbiome), the IgA-biome also is impaired. In the presence of enteric infection, oral vaccines, or an intestinal inflammatory disorder, the IgA-biome focuses on the pathogenic bacteria or foreign antigens, while in other chronic diseases associated with dysbiosis, the IgA-biome is reduced in capacity. Fecal microbiota transplantation (FMT), the use of …

Targeting Hyaluronic Acid Synthase-3 (Has3) For The Treatment Of Advanced Renal Cell Carcinoma, Jiaojiao Wang, Andre R Jordan, Huabin Zhu, Sarrah L Hasanali, Eric Thomas, Soum D Lokeshwar, Daley S Morera, Sung Alexander, Joseph Mcdaniels, Anuj Sharma, Karina Aguilar, Semih Sarcan, Tianyi Zhu, Mark S Soloway, Martha K Terris, Muthusamy Thangaraju, Luis E Lopez, Vinata B Lokeshwar

Journal Articles

BACKGROUND: Hyaluronic acid (HA) promotes cancer metastasis; however, the currently approved treatments do not target HA. Metastatic renal carcinoma (mRCC) is an incurable disease. Sorafenib (SF) is a modestly effective antiangiogenic drug for mRCC. Although only endothelial cells express known SF targets, SF is cytotoxic to RCC cells at concentrations higher than the pharmacological-dose (5-µM). Using patient cohorts, mRCC models, and SF combination with 4-methylumbelliferone (MU), we discovered an SF target in RCC cells and targeted it for treatment.

METHODS: We analyzed HA-synthase (HAS1, HAS2, HAS3) expression in RCC cells and clinical (n = 129), TCGA-KIRC (n = 542), and …

Intestinal Iga-Coated Bacteria In Healthy- And Altered-Microbiomes (Dysbiosis) And Predictive Value In Successful Fecal Microbiota Transplantation, Herbert L Dupont, Zhi-Dong Jiang, Ashley S Alexander, Andrew W Dupont, Eric L Brown

Journal Articles

IgA-coated bacteria in the gut (IgA-biome) provide a homeostatic function in healthy people through inhibition of microbial invaders and by protecting the epithelial monolayer of the gut. The laboratory methods used to detect this group of bacteria require flow cytometry and DNA sequencing (IgA-Seq). With dysbiosis (reduced diversity of the microbiome), the IgA-biome also is impaired. In the presence of enteric infection, oral vaccines, or an intestinal inflammatory disorder, the IgA-biome focuses on the pathogenic bacteria or foreign antigens, while in other chronic diseases associated with dysbiosis, the IgA-biome is reduced in capacity. Fecal microbiota transplantation (FMT), the use of …

Long-Term Use Of An Ankle-Foot Orthosis Intervention In Patients With Peripheral Artery Disease Using The Integrated Promoting Action On Research Implementation In Health Services (I-Parihs) Framework, Ayisha Bashir, Danae Dinkel, Iraklis Pipinos, Paul Estabrooks, Jason Johanning, Sara A. Myers

Journal Articles

Background

Peripheral artery disease (PAD) is a cardiovascular disease that limits patients' walking ability. Persistent ankle-foot orthosis (AFO) use may increase the distance patients can walk as well as physical activity.

Purpose

The purpose of the study was to determine the implementation and patients' perspectives related to the use or disuse of the AFO intervention six months post-intervention. This study was guided by a semi-structured interview and survey based on the integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) constructs.

Design

A convergent mixed methods design was used to evaluate participants' perceptions six months following a three-month AFO …

Cerebellar High-Grade Glioma: A Translationally Oriented Review Of The Literature, Ashley L B Raghu, Jason A Chen, Pablo A Valdes, Walid Ibn Essayed, Elizabeth Claus, Omar Arnaout, Timothy R Smith, E Antonio Chiocca, Pier Paolo Peruzzi, Joshua D Bernstock

Journal Articles

World Health Organization (WHO) grade 4 gliomas of the cerebellum are rare entities whose understanding trails that of their supratentorial counterparts. Like supratentorial high-grade gliomas (sHGG), cerebellar high-grade gliomas (cHGG) preferentially affect males and prognosis is bleak; however, they are more common in a younger population. While current therapy for cerebellar and supratentorial HGG is the same, recent molecular analyses have identified features and subclasses of cerebellar tumors that may merit individualized targeting. One recent series of cHGG included the subclasses of (1) high-grade astrocytoma with piloid features (HGAP, ~31% of tumors); (2) H3K27M diffuse midline glioma (~8%); and (3) …

Complete Corpus Callosotomy Using A Frameless Navigation Probe Through A Minicraniotomy In Children With Medically Refractory Epilepsy: A Case Series And Technical Note, Ahmed Belal, Gretchen Von Allmen, Indira Kommuru, Jeremy Lankford, John C Mosher, Manish Shah, Michael Funke, Michael Watkins, Rajan Patel

Journal Articles

Background:

Medically refractory epilepsy constitutes up to one-third of the epilepsy pediatric patients. Corpus callosotomy (CC) has been used for the treatment of medically refractory epilepsy in children with atonic seizures and generalized tonic–clonic (GTC) seizures. In this case series study, we are describing a novel technique for CC using the frameless navigation probe through a minicraniotomy.

Methods:

Thirteen pediatric patients with the diagnosis of medically refractory epilepsy predominantly GTC with drop attack who underwent extensive Phase I. An L-shape was done, then through a 4 × 3 cm craniotomy, we were able to open the interhemispheric fissure until the …

Risk Factors For Sars-Cov-2 Transmission In Close Contacts Of Adults At High Risk Of Infection Due To Occupation: Results From The Contact Tracing Strategy Of The Covida Epidemiological Surveillance Study In Bogotá, Colombia, In 2020-2021, Andrea Ramírez Varela, Sandra Contreras-Arrieta, Guillermo Tamayo-Cabeza, Leonardo Salas Zapata, Yuldor Caballero-Díaz, Luis Jorge Hernández Florez, Andrés Patiño Benavidez, Rachid Laajaj, Fernando De La Hoz, Giancarlo Buitrago Gutierrez, Silvia Restrepo, Eduardo Behrentz

Journal Articles

OBJECTIVES: To estimate the risk factors for SARS-CoV-2 transmission in close contacts of adults at high risk of infection due to occupation, participants of the CoVIDA study, in Bogotá D.C., Colombia.

SETTING: The CoVIDA study was the largest COVID-19 intensified sentinel epidemiological surveillance study in Colombia thus far, performing over 60 000 RT-PCR tests for SARS-CoV-2 infection. The study implemented a contact tracing strategy (via telephone call) to support traditional surveillance actions performed by the local health authority.

PARTICIPANTS: Close contacts of participants from the CoVIDA study.

PRIMARY AND SECONDARY OUTCOME MEASURES: SARS-CoV-2 testing results were obtained (RT-PCR with CoVIDA …

Hif1a-Dependent Induction Of Alveolar Epithelial Pfkfb3 Dampens Acute Lung Injury, Christine U Vohwinkel, Nana Burns, Ethan Coit, Xiaoyi Yuan, Eszter K Vladar, Christina Sul, Eric P Schmidt, Peter Carmeliet, Kurt Stenmark, Eva S Nozik, Rubin M Tuder, Holger K Eltzschig

Journal Articles

Acute lung injury (ALI) is a severe form of lung inflammation causing acute respiratory distress syndrome in patients. ALI pathogenesis is closely linked to uncontrolled alveolar inflammation. We hypothesize that specific enzymes of the glycolytic pathway could function as key regulators of alveolar inflammation. Therefore, we screened isolated alveolar epithelia from mice exposed to ALI induced by injurious ventilation to assess their metabolic responses. These studies pointed us toward a selective role for isoform 3 of the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3). Pharmacologic inhibition or genetic deletion of Pfkfb3 in alveolar epithelia (Pfkfb3loxP/loxP SPC-ER-Cre+ mice) was associated with profound increases in ALI during …

Molecular Markers In Maternal Blood Exosomes Allow Early Detection Of Fetal Alcohol Spectrum Disorders, Nune Darbinian, Armine Darbinyan, John Sinard, Gabriel Tatevosian, Nana Merabova, Faith D'Amico, Tarek Khader, Ahsun Bajwa, Diana Martirosyan, Alina K Gawlinski, Richa Pursnani, Huaqing Zhao, Shohreh Amini, Mary Morrison, Laura Goetzl, Michael E Selzer

Journal Articles

Prenatal alcohol exposure can cause developmental abnormalities (fetal alcohol spectrum disorders; FASD), including small eyes, face and brain, and neurobehavioral deficits. These cannot be detected early in pregnancy with available imaging techniques. Early diagnosis could facilitate development of therapeutic interventions. Banked human fetal brains and eyes at 9−22 weeks’ gestation were paired with maternal blood samples, analyzed for morphometry, protein, and RNA expression, and apoptotic signaling. Alcohol (EtOH)-exposed (maternal self-report) fetuses were compared with unexposed controls matched for fetal age, sex, and maternal race. Fetal brain-derived exosomes (FB-E) were isolated from maternal blood and analyzed for protein, RNA, and apoptotic …

Kras Inhibitor That Simultaneously Inhibits Nucleotide Exchange Activity And Effector Engagement, Cynthia V Pagba, Amit K Gupta, Ali K Naji, Dharini Van Der Hoeven, Kelly Churion, Xiaowen Liang, Jacob Jakubec, Magnus Hook, Yan Zuo, Marisela Martinez De Kraatz, Jeffrey A Frost, Alemayehu A Gorfe

Journal Articles

We describe a small molecule ligand ACA-14 (2-hydroxy-5-{[(2-phenylcyclopropyl) carbonyl] amino} benzoic acid) as an initial lead for the development of direct inhibitors of KRAS, a notoriously difficult anticancer drug target. We show that the compound binds to KRAS near the switch regions with affinities in the low micromolar range and exerts different effects on KRAS interactions with binding partners. Specifically, ACA-14 impedes the interaction of KRAS with its effector Raf and reduces both intrinsic and SOS-mediated nucleotide exchange rates. Likely as a result of these effects, ACA-14 inhibits signal transduction through the MAPK pathway in cells expressing mutant KRAS and …

Total Transfemoral Percutaneous Endovascular Aortic Arch Repair Using 3-Vessel Inner Branch Stent-Graft, Emanuel R Tenorio, Thanila A Macedo, Laura Ocasio, Marina Dias Neto, Guilherme B Barbosa Lima, Aidin Baghbani-Oskouei, Anthony L Estrera, Abhijeet Dhoble, Shao Feng Zhou, Gustavo S Oderich

Journal Articles

Endovascular repair has been introduced to decrease the morbidity and mortality associated with open surgical repair of aortic arch pathology. We illustrate total percutaneous transfemoral approach with a 3-vessel inner branch stent-graft to treat aortic arch aneurysm. (Level of Difficulty: Advanced.).

Total Transfemoral Percutaneous Endovascular Aortic Arch Repair Using 3-Vessel Inner Branch Stent-Graft, Emanuel R Tenorio, Thanila A Macedo, Laura Ocasio, Marina Dias Neto, Guilherme B Barbosa Lima, Aidin Baghbani-Oskouei, Anthony L Estrera, Abhijeet Dhoble, Shao Feng Zhou, Gustavo S Oderich

Journal Articles

Endovascular repair has been introduced to decrease the morbidity and mortality associated with open surgical repair of aortic arch pathology. We illustrate total percutaneous transfemoral approach with a 3-vessel inner branch stent-graft to treat aortic arch aneurysm. (Level of Difficulty: Advanced.).

Overqualified And Underrepresented: Gender Inequality In Pharmaceutical Patent Law, S. Sean Tu, Paul R. Gugliuzza, Amy Semet

Journal Articles

Pharmaceutical patents represent some of the most valuable intellectual property assets in the world: they can be worth billions of dollars if courts uphold their validity and find them infringed. But, if invalidated, generic drug manufacturers can get to market earlier, generating billions of dollars of revenue for themselves and creating enormous savings for consumers. Accordingly, drug patents are the product of careful, high-cost prosecution and are associated with high-stakes, bet-the-company litigation. But women lawyers are noticeably absent from pharmaceutical patent practice. This article reports an original empirical study finding that women comprise only one-third of the top pharmaceutical patent …

In-Depth Analysis Of Alternative Splicing Landscape In Multiple Myeloma And Potential Role Of Dysregulated Splicing Factors, Anil Aktas Samur, Mariateresa Fulciniti, Herve Avet-Loiseau, Michael A Lopez, Sanika Derebail, Jill Corre, Stephane Minvielle, Florence Magrangeas, Philippe Moreau, Kenneth C Anderson, Giovanni Parmigiani, Mehmet K Samur, Nikhil C Munshi

Journal Articles

Splicing changes are common in cancer and are associated with dysregulated splicing factors. Here, we analyzed RNA-seq data from 323 newly diagnosed multiple myeloma (MM) patients and described the alternative splicing (AS) landscape. We observed a large number of splicing pattern changes in MM cells compared to normal plasma cells (NPC). The most common events were alterations of mutually exclusive exons and exon skipping. Most of these events were observed in the absence of overall changes in gene expression and often impacted the coding potential of the alternatively spliced genes. To understand the molecular mechanisms driving frequent aberrant AS, we …

Structural Foundations Of Potassium Selectivity In Channelrhodopsins, Elena G Govorunova, Oleg A Sineshchekov, Leonid S Brown, Ana-Nicoleta Bondar, John L Spudich

Journal Articles

Potassium-selective channelrhodopsins (KCRs) are light-gated K+ channels recently found in the stramenopile protist Hyphochytrium catenoides. When expressed in neurons, KCRs enable high-precision optical inhibition of spiking (optogenetic silencing). KCRs are capable of discriminating K+ from Na+ without the conventional K+ selectivity filter found in classical K+ channels. The genome of H. catenoides also encodes a third paralog that is more permeable for Na+ than for K+. To identify structural motifs responsible for the unusual K+ selectivity of KCRs, we systematically analyzed a series of chimeras and mutants of this protein. We found that mutations of three critical residues in the …

A Flexible-Hazards Cure Model With Application To Patients With Soft Tissue Sarcoma, Can Xie, Xuelin Huang, Ruosha Li, Peter W T Pisters

Journal Articles

In medical research, it is often of great interest to have an accurate estimation of cure rates by different treatment options and for different patient groups. If the follow-up time is sufficiently long and the sample size is large, the proportion of cured patients will make the Kaplan-Meier estimator of survival function have a flat plateau at its tail, whose value indicates the overall cure rate. However, it may be difficult to estimate and compare the cure rates for all the subsets of interest in this way, due to the limit of sample sizes and curse of dimensionality. In the …

A Forehead Wearable Sensor For The Objective Measurement Of Chronic Pain, Marcus Orzabal, Ramo Naidu, Kasra Amirdelfan, Alireza Akhbardeh

Journal Articles

Chronic pain impacts one in five Americans and is difficult to manage, costing ~USD 600 billion annually. The subjective experience of pain is a complex processing of central nervous system input. Recent advances in magnetic resonance imaging revealed the prefrontal cortex as vital to the perception of pain and that changes in the cerebral hemodynamics can be used to detect painful sensations. Current pain monitoring is dependent on the subjective rating provided by patients and is limited to a single time point. We have developed a biomarker for the objective, real-time and continuous chronic pain assessment using proprietary algorithms termed …

The Impact Of Vitamin A Deficiency On Tuberculosis Progression, Brendan K Podell, Omowunmi Aibana, Chuan-Chin Huang, James E Dilisio, Macallister C Harris, David F Ackart, Kody Armann, Alexander Grover, Patrice Severe, Marc Antoine Jean Juste, Kathryn Dupnik, Randall J Basaraba, Megan B Murray

Journal Articles

BACKGROUND: Although previous studies have shown that vitamin A deficiency is associated with incident tuberculosis (TB) disease, the direction of the association has not been established. We investigated the impact of vitamin A deficiency on TB disease progression.

METHODS: We conducted a longitudinal cohort study nested within a randomized clinical trial among HIV-infected patients in Haiti. We compared serial vitamin A levels in individuals who developed TB disease to controls matched on age, gender, follow-up time, and time to antiretroviral therapy initiation. We also evaluated histopathology, bacterial load, and immune outcomes in TB infection in a guinea pig model of …

Ccl4 Regulates Eosinophil Activation In Eosinophilic Airway Inflammation, Hanh Hong Chu, Yoshiki Kobayashi, Dan Van Bui, Yasutaka Yun, Linh Manh Nguyen, Akitoshi Mitani, Kensuke Suzuki, Mikiya Asako, Akira Kanda, Hiroshi Iwai

Journal Articles

Eosinophilic chronic rhinosinusitis (ECRS) is a refractory airway disease accompanied by eosinophilic inflammation, the mechanisms of which are unknown. We recently found that CCL4/MIP-1β-a specific ligand for CCR5 receptors-was implicated in eosinophil recruitment into the inflammatory site and was substantially released from activated eosinophils. Moreover, it was found in nasal polyps from patients with ECRS, primarily in epithelial cells. In the present study, the role of epithelial cell-derived CCL4 in eosinophil activation was investigated. First, CCL4 expression in nasal polyps from patients with ECRS as well as its role of CCL4 in eosinophilic airway inflammation were investigated in an in …

Characterization Of Pulmonary Vascular Remodeling And Microrna-126-Targets In Copd-Pulmonary Hypertension., Khushboo Goel, Nicholas Egersdorf, Amar Gill, Danting Cao, Scott D Collum, Soma S Jyothula, Howard J Huang, Maor Sauler, Patty J Lee, Susan Majka, Harry Karmouty-Quintana, Irina Petrache

Journal Articles

BACKGROUND: Despite causing increased morbidity and mortality, pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD) patients (COPD-PH) lacks treatment, due to incomplete understanding of its pathogenesis. Hypertrophy of pulmonary arterial walls and pruning of the microvasculature with loss of capillary beds are known features of pulmonary vascular remodeling in COPD. The remodeling features of pulmonary medium- and smaller vessels in COPD-PH lungs are less well described and may be linked to maladaptation of endothelial cells to chronic cigarette smoking (CS). MicroRNA-126 (miR126), a master regulator of endothelial cell fate, has divergent functions that are vessel-size specific, supporting the survival …

Lipid-Nanoparticle-Mediated Delivery Of Docetaxel Prodrug For Exploiting Full Potential Of Gold Nanoparticles In The Treatment Of Pancreatic Cancer, Abdulaziz Alhussan, Nolan Jackson, Sarah Eaton, Nancy Dos Santos, Ingrid Barta, Josh Zaifman, Sam Chen, Yuen Yi C Tam, Sunil Krishnan, Devika B Chithrani

Journal Articles

Current chemoradiation therapy suffers from normal tissue toxicity. Thus, we are proposing incorporating gold nanoparticles (GNPs) and docetaxel (DTX), as they have shown very promising synergetic radiosensitization effects. Here, we explored the effect of a DTX prodrug encapsulated in lipid nanoparticles (LNP_DTX-P) on GNP uptake in pancreatic cancer models in vitro and in vivo. For the in vitro experiment, a pancreatic cancer cell line, MIA PaCa-2, was cultured and dosed with 1 nM GNPs and 45 nM free DTX or an equivalent dose of LNP_DTX-P. For the in vivo experiment, MIA PaCa-2 cells were implanted subcutaneously …

A General Catalyst Controlled Route To Prostaglandin F2a, Laura Cunningham, Sourabh Mishra, Leon Matthews, Stephen P Fletcher

Journal Articles

We report a general, catalyst-controlled route to prostaglandin F2_α and its analogues. The approach uses a Rh-catalyzed dynamic kinetic asymmetric Suzuki–Miyaura coupling reaction between a racemic bicyclic allyl chloride and alkenyl boronic esters bearing chiral alcohols to give cyclopentyl intermediates bearing 3 contiguous stereocenters. The route provides advanced intermediates in 99% ee as a single diastereoisomer in all cases examined, with the absolute stereochemistry of the cyclopentane core controlled by the ligand. Intermediates that could be used to produce prostaglandin analogues such as bimatoprost, latanoprost, fluprostenol, and cloprostenol were synthesized. The final two stereocenters were installed via Pd-catalyzed Tsuji–Trost …

Whole Genome Sequencing Identifies Structural Variants Contributing To Hematologic Traits In The Nhlbi Topmed Program, Marsha M Wheeler, Adrienne M Stilp, Shuquan Rao, Bjarni V Halldórsson, Doruk Beyter, Jia Wen, Anna V Mihkaylova, Caitlin P Mchugh, John Lane, Min-Zhi Jiang, Laura M Raffield, Goo Jun, Fritz J Sedlazeck, Ginger Metcalf, Yao Yao, Joshua B Bis, Nathalie Chami, Paul S De Vries, Pinkal Desai, James S Floyd, Yan Gao, Kai Kammers, Wonji Kim, Jee-Young Moon, Aakrosh Ratan, Lisa R Yanek, Laura Almasy, Lewis C Becker, John Blangero, Michael H Cho, Joanne E Curran, Myriam Fornage, Robert C Kaplan, Joshua P Lewis, Ruth J F Loos, Braxton D Mitchell, Alanna C Morrison, Michael Preuss, Bruce M Psaty, Stephen S Rich, Jerome I Rotter, Hua Tang, Russell P Tracy, Eric Boerwinkle, Goncalo R Abecasis, Thomas W Blackwell, Albert V Smith, Andrew D Johnson, Rasika A Mathias, Deborah A Nickerson, Matthew P Conomos, Yun Li, Unnur Þorsteinsdóttir, Magnús K Magnússon, Kari Stefansson, Nathan D Pankratz, Daniel E Bauer, Paul L Auer, Alex P Reiner

Journal Articles

Genome-wide association studies have identified thousands of single nucleotide variants and small indels that contribute to variation in hematologic traits. While structural variants are known to cause rare blood or hematopoietic disorders, the genome-wide contribution of structural variants to quantitative blood cell trait variation is unknown. Here we utilized whole genome sequencing data in ancestrally diverse participants of the NHLBI Trans Omics for Precision Medicine program (N = 50,675) to detect structural variants associated with hematologic traits. Using single variant tests, we assessed the association of common and rare structural variants with red cell-, white cell-, and platelet-related quantitative traits …

Stillbirth After Adolescent And Young Adult Cancer: A Population-Based Study, Caitlin C Murphy, Andrea C Betts, Marlyn A Allicock, L Aubree Shay, Sharice M Preston, Barbara A Cohn, Philip J Lupo, Sandi L Pruitt

Journal Articles

BACKGROUND: Gonadotoxic effects of cancer treatment may increase risk of adverse birth outcomes in adolescent and young adult (AYA, aged 15-39 years) women diagnosed with cancer. We estimated risk of stillbirth (fetal death of gestational age ≥20 weeks or weighing ≥350 grams) in a population-based sample of AYA women.

METHODS: AYA women diagnosed with cancer between January 1, 1995, and December 31, 2015, were identified using the Texas Cancer Registry and linked to live birth and fetal death certificates through December 31, 2016. Among AYA women, cumulative incidence of stillbirth was estimated by gestational age, and Poisson regression models identified …

Popdc1 Scaffolds A Complex Of Adenylyl Cyclase 9 And The Potassium Channel Trek-1 In Heart, Tanya A Baldwin, Yong Li, Autumn N Marsden, Susanne Rinné, Anibal Garza-Carbajal, Roland F R Schindler, Musi Zhang, Mia A Garcia, Venugopal Reddy Venna, Niels Decher, Thomas Brand, Carmen W Dessauer

Journal Articles

The establishment of macromolecular complexes by scaffolding proteins is key to the local production of cAMP by anchored adenylyl cyclase (AC) and the subsequent cAMP signaling necessary for cardiac functions. We identify a novel AC scaffold, the Popeye domain-containing (POPDC) protein. The POPDC family of proteins is important for cardiac pacemaking and conduction, due in part to their cAMP-dependent binding and regulation of TREK-1 potassium channels. We show that TREK-1 binds the AC9:POPDC1 complex and copurifies in a POPDC1-dependent manner with AC9 activity in heart. Although the AC9:POPDC1 interaction is cAMP-independent, TREK-1 association with AC9 and POPDC1 is reduced upon …

Plasma Growth Hormone Is A Potential Biomarker Of Response To Atezolizumab And Bevacizumab In Advanced Hepatocellular Carcinoma Patients, Yehia I Mohamed, Dan G Duda, Muhammad O Awiwi, Sunyoung S Lee, Lina Altameemi, Lianchun Xiao, Jeffrey S Morris, Robert A Wolff, Khaled M Elsayes, Rikita I Hatia, Aliya Qayyum, Shadi M Chamseddine, Asif Rashid, James C Yao, Armeen Mahvash, Manal M Hassan, Hesham M Amin, Ahmed Omar Kaseb

Journal Articles

INTRODUCTION: Hepatocellular carcinoma (HCC) has limited systemic therapy options when discovered at an advanced stage. Thus, there is a need for accessible and minimally invasive biomarkers of response to guide the selection of patients for treatment. This study investigated the biomarker value of plasma growth hormone (GH) level as a potential biomarker to predict outcome in unresectable HCC patients treated with current standard therapy, atezolizumab plus bevacizumab (Atezo/Bev).

MATERIALS AND METHODS: Study included unresectable HCC patients scheduled to receive Atezo/Bev. Patients were followed to determine progression-free survival (PFS) and overall survival (OS). Plasma GH levels were measured by ELISA and …

Identification Of Acenkps, A Committed Common Progenitor Population Of The Ilc1 And Nk Cell Continuum, Noe Rodriguez-Rodriguez, Paula A Clark, Mayuri Gogoi, Ana C F Ferreira, Bernhard Kerscher, Alastair Crisp, Helen E Jolin, Jane E Murphy, Meera Sivasubramaniam, Luisa Pedro, Jennifer A Walker, Morgan W D Heycock, Jacqueline D Shields, Jillian L Barlow, Andrew N J Mckenzie

Journal Articles

The development of innate lymphoid cell (ILC) transcription factor reporter mice has shown a previously unexpected complexity in ILC hematopoiesis. Using novel polychromic mice to achieve higher phenotypic resolution, we have characterized bone marrow progenitors that are committed to the group 1 ILC lineage. These common ILC1/NK cell progenitors (ILC1/NKP), which we call "aceNKPs", are defined as lineage-Id2+IL-7Rα+CD25-α4β7-NKG2A/C/E+Bcl11b-. In vitro, aceNKPs differentiate into group 1 ILCs, including NK-like cells that express Eomes without the requirement for IL-15, and produce IFN-γ and perforin upon IL-15 stimulation. Following reconstitution of Rag2-/-Il2rg-/- hosts, aceNKPs give rise to a spectrum of mature ILC1/NK cells …

Popdc1 Scaffolds A Complex Of Adenylyl Cyclase 9 And The Potassium Channel Trek-1 In Heart, Tanya A Baldwin, Yong Li, Autumn N Marsden, Susanne Rinné, Anibal Garza-Carbajal, Roland F R Schindler, Musi Zhang, Mia A Garcia, Venugopal Reddy Venna, Niels Decher, Thomas Brand, Carmen W Dessauer

Journal Articles

The establishment of macromolecular complexes by scaffolding proteins is key to the local production of cAMP by anchored adenylyl cyclase (AC) and the subsequent cAMP signaling necessary for cardiac functions. We identify a novel AC scaffold, the Popeye domain-containing (POPDC) protein. The POPDC family of proteins is important for cardiac pacemaking and conduction, due in part to their cAMP-dependent binding and regulation of TREK-1 potassium channels. We show that TREK-1 binds the AC9:POPDC1 complex and copurifies in a POPDC1-dependent manner with AC9 activity in heart. Although the AC9:POPDC1 interaction is cAMP-independent, TREK-1 association with AC9 and POPDC1 is reduced upon …