tbuckley/cabot-search huggingface dataset:
Abstract 15008: Improvement in Patient Ratings of Hypertension Care in a Pragmatic Cluster-randomized Trial of Home Blood Pressure Telemonitoring and Pharmacist Care (Hyperlink 3)
Authors: Karen L Margolis, Leif I Solberg, A Lauren Crain, Jeanette Y Ziegenfuss, Anna R Bergdall, MarySue Beran, Jeffrey P Anderson, Pamala A Pawloski, Daniel J Rehrauer, Christine Norton, Patricia K Haugen, Beverly B Green, Zeke J McKinney, Amy J Kodet, Deepika Appana, Rashmi Sharma, Nicole K Trower, Benjamin F Crabtree, Jacob L Haapala, Thomas E Kottke, Patrick J O'Connor
Journal: Circulation (2020)

Introduction: Patient ratings of their experience of care are part of the “Triple Aim”. Improvements are highly valued by health care organizations, but are hard to achieve. Hypothesis: We tested the effect of a telehealth intervention on satisfaction with hypertension care. Methods: Hyperlink 3 is an ongoing pragmatic cluster-randomized trial in 3072 patients with uncontrolled hypertension in 21 primary care clinics in HealthPartners, an integrated health system in Minnesota and Wisconsin. Clinics were randomized to Clinic-based Care (CC, 9 clinics, 1648 patients) or Telehealth Care (TC, 12 clinics, 1424 patients). CC patients received guideline-based hypertension care in face-to-face visits. TC patients were additionally offered home blood pressure (BP) telemonitoring with pharmacist care management. Patients were surveyed at baseline and after 6 months of study enrollment and asked to rate their hypertension care in the previous 6 months on a scale of 0-10. We compared change in the proportion of patients rating their care at the highest level (9 or 10). Results: In the TC group, about 37% of patients attended an intake pharmacist visit and 434 (30%) participated in home BP telemonitoring. Baseline surveys were completed by 1719 (56%) of patients at baseline (goal 50% completion) and 1301 (76%) of those completing the baseline survey completed the 6 month survey (goal 75% completion). Baseline survey respondents’ mean age was 62 y (non-respondents 58 y), 46% were men (non-respondents 48%), 19% were black (non-respondents 20%), and mean BP was 164/93 mm Hg (non-respondents 164/95 mm Hg.) Nearly all patients (over 90%) took antihypertensive medications (median 2). Hypertension care ratings of 9 or 10 were 27.9% at baseline and 30.2% at 6 months in CC, compared with 29.0% at baseline and 39.5% at 6 months in TC. The odds ratio (OR) for change over time in 9 or 10 ratings was 1.11 (95% CI 0.87 - 1.42) in CC, and 1.61 (95% CI 1.26 - 2.07) in TC. The OR for change in 9 or 10 ratings over time in TC vs CC was 1.45 (95% CI 1.03 - 2.06). Conclusions: Home BP telemonitoring with pharmacist care management increased the proportion of patients who highly rated their experience of hypertension care, even though only a minority of the TC patients received the intervention.
KLF4-dependent phenotypic modulation of smooth muscle cells has a key role in atherosclerotic plaque pathogenesis
Authors: Laura S Shankman, Delphine Gomez, Olga A Cherepanova, Morgan Salmon, Gabriel F Alencar, Ryan M Haskins, Pamela Swiatlowska, Alexandra A C Newman, Elizabeth S Greene, Adam C Straub, Brant Isakson, Gwendalyn J Randolph, Gary K Owens
Journal: Nature Medicine (2015)
Endotoxinemia Accelerates Atherosclerosis Through Electrostatic Charge–Mediated Monocyte Adhesion
Authors: Ariane Schumski, Almudena Ortega-Gómez, Kanin Wichapong, Carla Winter, Patricia Lemnitzer, Joana R. Viola, Mayra Pinilla-Vera, Eduardo Folco, Victor Solis-Mezarino, Moritz Völker-Albert, Sanne L. Maas, Chang Pan, Laura Perez Olivares, Janine Winter, Tilman Hackeng, Mikael C.I. Karlsson, Tanja Zeller, Axel Imhof, Rebecca M. Baron, Gerry A.F. Nicolaes, Peter Libby, Lars Maegdefessel, Frits Kamp, Martin Benoit, Yvonne Döring, Oliver Soehnlein
Journal: Circulation (2020)

Background: Acute infection is a well-established risk factor of cardiovascular inflammation increasing the risk for a cardiovascular complication within the first weeks after infection. However, the nature of the processes underlying such aggravation remains unclear. Lipopolysaccharide derived from Gram-negative bacteria is a potent activator of circulating immune cells including neutrophils, which foster inflammation through discharge of neutrophil extracellular traps (NETs). Here, we use a model of endotoxinemia to link acute infection and subsequent neutrophil activation with acceleration of vascular inflammation Methods: Acute infection was mimicked by injection of a single dose of lipopolysaccharide into hypercholesterolemic mice. Atherosclerosis burden was studied by histomorphometric analysis of the aortic root. Arterial myeloid cell adhesion was quantified by intravital microscopy. Results: Lipopolysaccharide treatment rapidly enhanced atherosclerotic lesion size by expansion of the lesional myeloid cell accumulation. Lipopolysaccharide treatment led to the deposition of NETs along the arterial lumen, and inhibition of NET release annulled lesion expansion during endotoxinemia, thus suggesting that NETs regulate myeloid cell recruitment. To study the mechanism of monocyte adhesion to NETs, we used in vitro adhesion assays and biophysical approaches. In these experiments, NET-resident histone H2a attracted monocytes in a receptor-independent, surface charge–dependent fashion. Therapeutic neutralization of histone H2a by antibodies or by in silico designed cyclic peptides enables us to reduce luminal monocyte adhesion and lesion expansion during endotoxinemia. Conclusions: Our study shows that NET-associated histone H2a mediates charge-dependent monocyte adhesion to NETs and accelerates atherosclerosis during endotoxinemia.
Abstract 15398: Standing Breathless: A Case of Platypnea-Orthodeoxia Syndrome
Authors: Adam S Vohra, Pritha Subramanyam, Harsimran S Singh
Journal: Circulation (2020)

A 67-year old women with a history of metastatic endometrial cancer, prior pulmonary embolism (PE) (on Xarelto) and mitral valve prolapse presented for 2-3 weeks of exertional dyspnea. Patient presented to oncology clinic with oxygen saturation (SpO2) in the mid-70% on room air requiring supplemental oxygen, and eventually high flow nasal cannula (HFNC). She was transferred to our cardiac intensive care unit for further management of her hypoxia. Physical exam was notable for decreasing SpO2 from supine (99%) to sitting (88%) to standing (79%). In this patient with metastatic cancer, differential diagnosis for hypoxia was broad including pneumonia, metastatic pulmonary disease, doxorubicin-induced cardiomyopathy, and PE. CT chest showed no signs of pulmonary edema, pneumonia, lung metastases, or PE. Transthoracic echocardiogram showed normal left and right ventricular function with moderate aortic regurgitation and mitral regurgitation. However, agitated saline injection showed right to left flow consistent with intraatrial shunt. Transesophageal echocardiogram confirmed large patent foramen ovale (PFO) with atrial septal aneurysm. Given physical examination findings, presence of PFO, and structural abnormalities of intraatrial septum, platypnea-orthodeoxia syndrome (POS) was considered. Right heart catheterization was completed to evaluate shunt physiology and showed unremarkable pressures (RA 1, RV 22/1, PCWP 3, PA 20/3, and LA 2). Venous oxygen saturations did not show any step-up suggesting left to right shunt. Exercise challenge did not result in any significant change in PA or PCWP pressures. Given persistent concern for POS without other clear diagnosis, patient underwent percutaneous closure of PFO with a 30mm Gore Cardioform septal occluder. Patient had resolution of her exertional hypoxia following procedure and was discharged home the next day. The case discusses 1) the importance of history of and physical exam in narrowing diagnosis, 2) utilization of multimodality imaging to evaluate intraatrial shunts, and 3) use of percutaneous methods for PFO closure.
Long-Term Ambient Air Pollution Exposures and Brain Imaging Markers in Korean Adults: The Environmental Pollution-Induced Neurological EFfects (EPINEF) Study
Authors: Jaelim Cho, Young Noh, Sun Young Kim, Jungwoo Sohn, Juhwan Noh, Woojin Kim, Seong-Kyung Cho, Hwasun Seo, Gayoung Seo, Seung-Koo Lee, Seongho Seo, Sang-Baek Koh, Sung Soo Oh, Hee Jin Kim, Sang Won Seo, Dae-Seock Shin, Nakyoung Kim, Ho Hyun Kim, Jung Il Lee, Changsoo Kim
Journal: Environmental Health Perspectives (2020)

Background: Only a limited number of neuroimaging studies have explored the effects of ambient air pollution in adults. The prior studies have investigated only cortical volume, and they have reported mixed findings, particularly for gray matter. Furthermore, the association between nitrogen dioxide (NO2) and neuroimaging markers has been little studied in adults. Objectives: We investigated the association between long-term exposure to air pollutants (NO2, particulate matter (PM) with aerodynamic diameters of ≤10μm (PM10) and ≤2.5μm (PM2.5), and neuroimaging markers. Methods: The study included 427 men and 530 women dwelling in four cities in the Republic of Korea. Long-term concentrations of PM10, NO2, and PM2.5 at residential addresses were estimated. Neuroimaging markers (cortical thickness and subcortical volume) were obtained from brain magnetic resonance images. A generalized linear model was used, adjusting for potential confounders. Results: A 10-μg/m3 increase in PM10 was associated with reduced thicknesses in the frontal [–0.02mm (95% CI: –0.03, –0.01)] and temporal lobes [–0.06mm (95% CI: –0.07, –0.04)]. A 10-μg/m3 increase in PM2.5 was associated with a thinner temporal cortex [–0.18mm (95% CI: –0.27, –0.08)]. A 10-ppb increase in NO2 was associated with reduced thicknesses in the global [–0.01mm (95% CI: –0.01, 0.00)], frontal [–0.02mm (95% CI: –0.03, –0.01)], parietal [–0.02mm (95% CI: –0.03, –0.01)], temporal [–0.04mm (95% CI: –0.05, –0.03)], and insular lobes [–0.01mm (95% CI: –0.02, 0.00)]. The air pollutants were also associated with increased thicknesses in the occipital and cingulate lobes. Subcortical structures associated with the air pollutants included the thalamus, caudate, pallidum, hippocampus, amygdala, and nucleus accumbens. Discussion: The findings suggest that long-term exposure to high ambient air pollution may lead to cortical thinning and reduced subcortical volume in adults. https://doi.org/10.1289/EHP7133
Treating exuberant, non-resolving inflammation in the lung; Implications for acute respiratory distress syndrome and COVID-19
Authors: Derek W. Gilroy, Roel P.H. De Maeyer, Mark Tepper, Alastair O’Brien, Mohib Uddin, Judy Chen, Daniel R. Goldstein, Arne N. Akbar
Journal: Pharmacology & Therapeutics (2020)
Prostate Cancer Liver Metastases Presenting as Relatively Photopenic Lesions on 18F-Fluciclovine PET/CT
Authors: Ali Baiomy, Lucia Martiniova, Eleni Efstathiou, David M. Schuster, Gregory Ravizzini
Journal: Clinical Nuclear Medicine (2020)

Abstract A 66-year-old man with prostate adenocarcinoma status post radical retropubic prostatectomy and bilateral pelvic lymph node dissection, followed by salvage external beam radiation therapy to the prostate bed 1 year after surgery. Over the course of 17 years, the patient underwent multiple lines of systemic treatment for recurrent disease. He was referred for restaging 18 F-fluciclovine PET/CT due to rising serum prostate-specific antigen levels. Contrast-enhanced 18 F-fluciclovine PET/CT images demonstrated multiple new liver metastases, which were relatively photopenic in comparison with the physiologic radiotracer activity in the surrounding normal liver parenchyma.
Abstract 15916: Role of Small-cajal Body Associated RNAs (scaRNAs) in Regulation of Cardiomyogenesis
Authors: Shivaani Kirankumar, VINOTH SIGAMANI, Sheeja Rajasingh, Jayavardini Vasanthan, Narasimman Gurusamy, Douglas C Bittel, Rajasingh Johnson
Journal: Circulation (2020)

Introduction: The requirement of non-coding RNAs particularly scaRNAs are playing a critical role in alternative splicing and maturation of mRNAs. Dysregulated splicing of mRNAs has been shown to cause heart defects. In this study, we are comparing the role of scaRNAs during differentiation of induced pluripotent stem cells (iPSCs) into cardiomyocytes (iCMCs) from normal individual and Noonan syndrome (NS) patient. We have selected NS patient cells because it is an autosomal dominant genetic disorder which leads to cardiomyopathy and congenital heart defects in humans. Hypothesis: We hypothesize that scaRNA1 and scaRNA20 have a significant role in the development of cardiomyocytes, and these scaRNAs are dysfunctional in iCMCs derived from NS. Methods and Results: We have compared the normal skin fibroblast-derived iPSCs (N-iPSCs) and N-iCMCs with NS patient-derived NS-iPSCs and NS-iCMCs using quantitative RT-PCR, Western blot and immunofluorescence analyses. We also used the knockdown and overexpression of scaRNA1 and scaRNA20 approaches to delineate the importance of these scaRNAs during cardiomyogenesis. Our qRT-PCR data showed a significantly lower expression of scaRNA1 and scaRNA20 (Fig. A) as well as the cardiac-specific genes CTT and GATA4 (Fig. B) in NS-iCMCs when compared to the normal iCMCs. Furthermore, the qRT-PCR data from the scaRNA20 overexpressed N-iCMC showed an increased expression of cardiac-specific genes (Fig. C) when compared to the N-iCMCs. These studies clearly indicate that scaRNA1 and scaRNA20 plays an important role in cardiomyogenesis. Further studies are underway to explore the mechanisms of these scaRNAs in regulation of cardiac genes. Conclusions: Our findings indicate that scaRNA1 and scaRNA20 are involved in mRNA splicing and maturation of cardiac genes. Moreover, these scaRNAs are dysfunctional in NS patient’s iCMCs and targeting these molecules will have a therapeutic potential for a patient with NS.
Prediction of Health-related Quality of Life and Hospitalization in Pulmonary Arterial Hypertension: The Pulmonary Hypertension Association Registry
Authors: Jeff Min, David Badesch, Murali Chakinala, Jean Elwing, Robert Frantz, Evelyn Horn, James Klinger, Matthew Lammi, Sula Mazimba, Jeffrey Sager, Oksana Shlobin, Marc Simon, Thenappan Thenappan, Daniel Grinnan, Corey Ventetuolo, Nadine Al-Naamani, Abhijit Raval, Amresh Raina, Anna Hemnes, Charles Burger, D. Dunbar Ivy, Delphine Yung, Dianne Zwicke, Erika Berman-Rosenzweig, Gautam Ramani, Granthem Farr, H. James Ford, James Runo, Jeffrey Fineman, Jeremy Feldman, John Swisher, John Ryan, John Wesley McConnell, Kenneth Presberg, Kishan Parikh, Linda Cadaret, Mark Avdalovic, Michael Duncan, Michael Eggert, Nidhy Varghese, Paul Boyce, Peter Leary, Raymond Foley, R. James White, Robert Frantz, Roham Zamanian, Russel Hirsch, Sahil Bakshi, Sonja Bartolome, Steven Kawut, Stephen Mathai, Teresa De Marco, Timothy Williamson, Todd Bull
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
Abstract 14930: Involvement of Chloride Channel (clic) in Myocardial Fibrosis of Pressure-overload Model Mice and Dilated Cardiomyopathy Patients
Authors: Gaku Oguri, Toshiaki Nakajima, Nomura Seitaro, Nakajima Takahumi, Hironobu Kikuchi, Syotaro Obi, Teruo Inoue, Komuro Issei
Journal: Circulation (2020)

Introduction: Pressure overload induces cardiac hypertrophy, electrical remodeling due to changes in various channels, and eventually leads to fibrosis, hardening of the heart, left ventricular diastolic dysfunction, and heart failure. Chloride channels (chloride intracellular channels, Clic) are localized in both plasma membranes and intracellular organelles of various cells, and have recently been reported to be associated with atrial fibrosis. In this study, we examined single-cell RNA-seq analysis of cardiomyocytes for changes in Clic using a pressure overload model due to transverse aortic coarctation (TAC). In addition, a similar analysis was performed on ventricular myocytes in dilated cardiomyopathy. Methods: Single ventricular myocytes were collected from the free wall of the left ventricle after TAC by collagenase treatment in the cardiac hypertrophy phase (3 days after TAC, 1 or 2 weeks (W)) and the heart failure phase (4,8W). The expression of various genes in ventricular myocytes was analyzed for single cells by RNA-seq and compared with sham mice. In addition, a similar study was performed from single ventricular myocytes obtained from dilated cardiomyopathy patients and donors. Results: The expression of myosin heavy chain β (Myh7), a fetal gene, was increased by pressure overload, but the expression of BNP and ANP genes was increased along with the expression of adult Myh6. Regarding Clic, Clic1,4 and 5 increased as compared with Sham mice. Clic1, Clic1 and 4 increased from 3d, and at 8W, Clic1, 4, and 5 also increased . The expression level of these Clic genes is associated with the genes associated with fibrosis (Col4a1, 4a2, 6a2, connective tissue growth factor (CTGF), transforming growth factor-beta 2 (TGFβ2). The KEGG pathway analysis using DAVID for genes with significant associations with Clic1,4, and 5 revealed a strong association with activation of Focal adhesion pathway. Single cell RNA-seq analysis of single ventricular myocytes from patients with dilated cardiomyopathy also showed a increase in CLIC4 and 5 genes compared to healthy donors. Conclusions: Single cell RNA of ventricular myocytes -seq analysis revealed the involvement of chloride channel Clic in myocardial fibrosis and structural remodeling in failing hearts.
Overexpression of the PSMB9 component of the proteasome in early stage, node negative breast cancer is prognostic for an increased risk of early relapse or death
Authors: Clark M. Whitehead, Ramona Nelson, Roxanne Hudson, Marquetta Gore, Raphael Marcelpoil, Didier Morel, Jan Hessling, Doug Malinowski, Tim Fischer
Journal: Cancer Research (2005)

3144  PSMB9 is a member of the beta subunit of the 20s human proteasome. The ubiquitin-proteasome plays a pivotal role in normal protein homeostasis and is critical in many cancer-related cellular processes. Increased proteolytic activity has been implicated in the pathogenesis of multiple cancers including breast cancer. The regulation of many key transcription factors and signal transduction proteins by the ubiquitin-proteasome is crucial for the control of many cellular processes, including cell cycle progression, apoptosis and drug resistance. We investigated the prognostic utility of PSMB9 overexpression in early stage, lymph node negative breast cancers. A monoclonal antibody to PSMB9 was generated and optimized to label, by immunohistochemistry (IHC), formalin fixed paraffin embedded breast tumors. Two independent cohorts of breast tumors were utilized. Cohort #1 was composed of 207 tumors (86% T1N0 or T2N0) with a minimum 5-year follow-up. Disease recurrence or death within 5 years was considered a bad outcome. This 1st cohort was composed of 63% good and 37% bad outcome tumors. Cohort #2 was composed of 220 chemo naive tumors (91% T1N0 or T2N0) with a minimum 10-year follow up. Disease recurrence or death within 10 years was considered a bad outcome. This 2nd cohort was composed of 70% good and 30% bad outcome tumors. A pathologist scored the labeled tumors manually and by utilizing the Interactive Histology Imaging System (IHIS). Within the 1st cohort, overexpression of PSMB9 identified the bad outcome tumors with a specificity and sensitivity of .94/.11 with manual scoring and .72/.39 using the IHIS system. Within the 2nd cohort, overexpression of PSMB9 identified the bad outcome tumors with a specificity and sensitivity of .84/.20 with manual scoring and .94/.14 using the IHIS system. This resulted in PSMB9 having a positive predictive value ranging from .38 to .53. PSMB9 displayed significant prognostic utility within our two independent cohorts of early stage lymph node negative breast cancer.
Metabolic Response by 18F-FDG PET/CT in Metastatic Malignant Struma Ovarii Treated With Targeted Therapies
Authors: Romain-David Seban, Laurence Bozec, Camila Nascimento-Leite, Laurence Champion
Journal: Clinical Nuclear Medicine (2020)

Malignant struma ovarii (MSO) is a rare malignant ovarian tumor, histologically identical to differentiated thyroid cancers. Given the rarity of this disease, there are no treatment guidelines, and the place of imaging for response assessment remains controversial. We report a metabolic response assessed by F-FDG PET/CT in a 71-year-old woman with radioiodine-refractory metastatic MSO treated by targeted therapies (first line with lenvatinib and second line with pazopanib). This case of exceptional response also highlights the usefulness of F-FDG PET/CT for therapeutic assessment of targeted drugs in such a rare clinical entity of malignant MSO.
Pulmonary infections complicating ARDS
Authors: Charles-Edouard Luyt, Lila Bouadma, Andrew Conway Morris, Jayesh A. Dhanani, Marin Kollef, Jeffrey Lipman, Ignacio Martin-Loeches, Saad Nseir, Otavio T. Ranzani, Antoine Roquilly, Matthieu Schmidt, Antoni Torres, Jean-François Timsit
Journal: Intensive Care Medicine (2020)
New insights into molecules and pathways of cancer metabolism and therapeutic implications
Authors: Zhenye Tang, Zhenhua Xu, Xiao Zhu, Jinfang Zhang
Journal: Cancer Communications (2020)

Cancer cells are abnormal cells that can reproduce and regenerate rapidly. They are characterized by unlimited proliferation, transformation and migration, and can destroy normal cells. To meet the needs for cell proliferation and migration, tumor cells acquire molecular materials and energy through unusual metabolic pathways as their metabolism is more vigorous than that of normal cells. Multiple carcinogenic signaling pathways eventually converge to regulate three major metabolic pathways in tumor cells, including glucose, lipid, and amino acid metabolism. The distinct metabolic signatures of cancer cells reflect that metabolic changes are indispensable for the genesis and development of tumor cells. In this review, we report the unique metabolic alterations in tumor cells which occur through various signaling axes, and present various modalities available for cancer diagnosis and clinical therapy. We further provide suggestions for the development of anti-tumor therapeutic drugs.