tbuckley/cabot-search huggingface dataset:
Extracellular matrix proteins in metastases to the liver – Composition, function and potential applications
Authors: Hanna Nyström
Journal: Seminars in Cancer Biology (2020)

The rising evidence of the tumor microenvironment (TME) and its role in cancer have made this an area of increased research efforts. The focus is both on the primary tumor but also on the metastatic setting. The TME though, does not only consist of the non-malignant cells of a tumor, but also of the acellular compartment: The Extracellular Matrix (ECM). The liver is a common organ for metastasis of many cancers and for some of these cancers' liver surgery is a standard treatment with long-term cure, whereas for other cancers not considered meaningful. Blood supply and anatomical reasons plays one part for the establishment of liver metastasis. It is however a well-known fact that the "soil" of a metastatic organ is of utter importance in the process of metastasis. The "soil" consists of the TME where the ECM is a critical and active part. This review focuses what is known about the normal ECM of the human liver, what is known about ECM proteins in human liver metastasis, challenges of studying the ECM in liver metastases and lastly, potential applications of this field of knowledge.
SKP2 My Lou, My Darling
Authors: Sydney L. Lambert, Kevin B. Jones
Journal: Cancer Research (2020)

Abstract Myxofibrosarcoma and undifferentiated pleomorphic sarcoma (UPS) lack specific molecular underpinnings, show high rates of metastasis, and display limited responsiveness to current therapies, making them challenging cancers both to treat and to study. It has been noted that MFS and UPS frequently lose function of the tumor suppressor genes RB1 and TP53. In this issue of Cancer Research, Li and colleagues demonstrate that proliferation in RB1- and TP53-deficient MFS and UPS depends on SKP2; inhibiting SKP2 with the neddylation inhibitor, pevonedistat, halts tumor growth in a panel of patient-derived xenografts. This renders the oncogenic protein SKP2 a promising therapeutic target. See related article by Li et al., p. 2461
Impact of Cardiopulmonary Resuscitation on Survival in Cancer Patients
Authors: Dana E. Giza, Jordan Graham, Teodora Donisan, Dinu V. Balanescu, John Crommet, Gregory Botz, Cristina Gutierrez, Mariberta Vidal, Rodrigo Mejia, Cezar Iliescu
Journal: JACC CardioOncology (2020)

Cancer patients have particularly low rates of return of spontaneous circulation (ROSC) and survival to hospital discharge following cardiopulmonary resuscitation (CPR) compared with non-cancer patients ([1][1]). The quality of life at discharge of those who survive after CPR is often diminished,
シロスタゾールによる末梢インターベンションの十分治療(STOP-IC)研究においてシロスタゾールは大腿膝か病変に対する血管内治療後の血管造影的再狭窄を縮小する | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Yokoi Hiroyoshi, Iida Osamu, Soga Yoshimistu, Nanto Shinsuke
Journal: Circulation (2013)
microRNA regulation of chemoresistance in non-small cell lung cancer (NSCLC)
Authors: Liqin Du, Rachel Greer, Jeoffrey Schageman, Adi Gazdar, Scott Hammond, Michael White, John Minna, Alexander Pertsemlidis
Journal: Cancer Research (2008)

5042  We are using a combination of in silico and in vitro approaches to address the questions of whether microRNA expression profiles correlate with chemotherapy sensitivity/resistance in lung cancers, whether microRNAs play a functional role in drug sensitivity/resistance of lung cancer cells and whether microRNA expression levels can be manipulated to increase drug sensitivity in cultured lung cancer cells. We have developed a panel of lung cancer and immortalized normal lung epithelial lines, on which we have measured in vitro sensitivity profiles to drugs commonly used in the treatment of lung cancer (which can show variations of >1,000 fold) and mRNA expression profiles (providing gene expression signatures for sensitivity/resistance). We profiled microRNA expression in a subset of 20 of these cell lines, and identified microRNAs that that are differentially expressed between cancer and normal and between drug sensitive and resistant NSCLCs. We correlated microRNA expression levels with drug sensitivity profiles, and developed a computational method to predict interactions between microRNAs and mRNA 3’UTRs. We have identified several microRNAs with expression profiles that are inversely correlated with response to drug treatment in cultured cells. We have transfected chemoresistant NSCLCs with stabilized mimics of these microRNAs and observed a 200- to 300-fold increase in sensitivity to paclitaxel. We predicted that a number of genes potentially related to drug resistance are regulatory targets of these microRNAs, including tubulin- and microtubule-associated protein kinases. Combining the predictions with a high-throughput siRNA screen, we identified 20 candidate regulatory targets of microRNAs relevant to chemosensitivity. Several of these predicted targets confer sensitivity to paclitaxel when knocked down by siRNA. These data suggest that microRNAs can be both diagnostic of and modulate the response of lung cancers to chemotherapy.
FRI0318 REAL-LIFE EVALUATION OF HEALTH STATUS USING ASAS HEALTH INDEX ON PATIENTS WITH AXIAL AND PERIPHERAL SPONDYLOARTHRITIS IN ARGENTINA
Authors: V. Martire, P. Girard Bosch, C. Airoldi, M. Benegas, V. Cosentino, J. Marin, V. Duarte, J. M. Bande, M. J. Gamba, F. Sommerfleck, P. Gonzalez, D. Vila, M. Oliver, L. Garcia, E. Velozo, E. Kerzberg, J. Tapia, M. Cosatti, P. Giorgis, L. L. Macias Oviedo, E. Schneeberger, R. Nieto, M. García, S. Scarafia
Journal: Annals of the Rheumatic Diseases (2020)

Background: The questionnaire “Assessment of Spondyloarthritis international Society Health Index” (ASAS HI) was developed to measure functionality and health status in patients with spondyloarthritis (SpA) 1 . Objectives: To describe the state of health measured by ASAS HI in Argentinian patients with SpA and to evaluate factors associated with poor health. Methods: Analytical, cross sectional, multicenter study. Patients with SpA according to ASAS criteria were consecutively included from 15 Argentinian centers. Statistical analysis: frequencies and percentages (%), mean and standard deviation (SD) or median and interquartile range (IQR). Bivariate analysis and logistic regression were performed to evaluate the factors associated with poor health status (ASAS HI &gt; or equal to 12). Correlation with other parameters was evaluated by Spearman correlation. Results: We included 274 patients with a mean age 49 (SD 14) years, median disease duration 60 month (IQR 24-135), 155 (56.6%) of patients are male, 47% (n:129) axial SpA and 52.9 (n:145) peripheral SpA. One hundred and nine patients (43.4%) presented good health status, 117 (42.7%) had moderate state of health and 38 (13.9%) had poor health. In the bivariate analyses patients with ASAS health index greater than or equal to 12 (poor status), were older [54 (11) vs 48 (14), p: 0.01], had higher disease duration [11(IQR 57-192) vs 60 (IQR 24-120), p: 0.02], more hypertension [20 (52.6%) vs 67 (28.4%), p:0.004], more diabetes mellitus [10 (26.3%) vs 22(9.3%), p: 0.006], depression [6 (15.8%) vs 10 (4.2%), p:0.013], anxiety [8 (21%) vs (22 (9.3%),p:0.046], less years of education [9.8 (SD 3.5) vs 13 (SD 10), p:0.001], higher ASQol [12.6 (SD 4.6) vs 5.7 (SD4), p &lt; 0.001], BASFI [7(SD2) vs 4(SD6), p: 0.001], DAS28 [4.71 (SD3.2) vs 2.8 (SD1),p: &lt;0.001]. In the multivariate analyses the following variables were independently associated with poor health status: duration of disease, ASQol and DAS28. ASAS HI showed positive correlation with the following parameters: BASDAI (r:0.67, p&lt; 0.001), HAQ (r:0.54, p&lt; 0.001), ASDAS (r:0.67, p&lt; 0.001), ASQol (r:0.80, p&lt; 0.001), BASFI (r:0.72, p&lt; 0.001) and DAS28 (0.56, p&lt; 0.001). Conclusion: Poor health status is associated with disease activity, poor quality of life and functional activity. ASAS HI has a good correlation with other parameters to evaluate SpA, reinforcing the construct validity of this new tool. References: [1]Kiltz U, et al . Ann Rheum Dis 2018; 0 :1–7. Disclosure of Interests: None declared
FRI0584 SCREENING AND IDENTIFICATION OF BIOMARKERS IN MYOSITIS
Authors: W. Liu, X. Zhang
Journal: Annals of the Rheumatic Diseases (2020)

Background: Myositis, including dermatomyositis and polymyositis, is autoimmune disorders that is characterized by muscle degeneration in the proximal extremities, with the complications of weakness of muscles, interstitial lung disease and vascular lesions, even leading to death in an acute progressive process [1,2] . However, the molecular mechanisms of myositis are rarely understood. Objectives: Identify the candidate genes in myositis. Methods: Microarray datasets GSE128470, GSE48280 and GSE39454 were extracted from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) and function enrichment analyses were conducted. The protein-protein interaction network and the analyses of hub genes were performed with STRING and Cytoscape. Results: There were 98 DEGs, of which the function and pathways enrichment analyses showed defense response, immune response, response to virus, inflammatory response, response to wounding, cell adhesion, cell proliferation, cell death and macromolecule metabolic process. 20 hub genes were identified, of which 7 including IRF9 TRIM22 MX2 IFITM1 IFI6 IFI44 IFI44L had not been reported in the literature, related to the response to virus, immune response, transcription from RNA polymerase II promoter, cell apoptosis, cell death. The verification analysis about the 7 genes in GSE128314 showed significant differences in myositis. Conclusion: In conclusion, DEGs and hub genes identified in our study showed the potential molecular mechanisms in myositis, providing the helpful targets for diagnosis and clinical strategy of myositis. References: [1] Wu H, Geng D, Xu J. An approach to the development of interstitial lung disease in dermatomyositis: a study of 230 cases in China[J]. Journal of International Medical Research. 2013;41(2):493–501. [2] Fathi M, Dastmalchi M, Rasmussen E, Lundberg IE, Tornling G. Interstitial lung disease, a common manifestation of newly diagnosed polymyositis and dermatomyositis[J]. Annals of the Rheumatic Diseases. 2004;63(3):297–301. Figure 1. The protein-protein interaction network of 20 hub genes Figure 2. 7 genes in GSE128314 showed significant differences in myositis Acknowledgments: The authors acknowledge the efforts of the Gene Expression Omnibus (GEO) database. The interpretation and reporting of these data are the sole responsibility of the authors. Disclosure of Interests: None declared
BGVD: An Integrated Database for Bovine Sequencing Variations and Selective Signatures
Authors: Ningbo Chen, Weiwei Fu, Jianbang Zhao, Jiafei Shen, Qiuming Chen, Zhuqing Zheng, Hong Chen, Tad S. Sonstegard, Chuzhao Lei, Yu Jiang
Journal: Genomics Proteomics & Bioinformatics (2020)

Abstract Next-generation sequencing has yielded a vast amount of cattle genomic data for global characterization of population genetic diversity and identification of genomic regions under natural and artificial selection. However, efficient storage, querying, and visualization of such large datasets remain challenging. Here, we developed a comprehensive database, the Bovine Genome Variation Database (BGVD). It provides six main functionalities: gene search, variation search, genomic signature search, Genome Browser, alignment search tools, and the genome coordinate conversion tool. BGVD contains information on genomic variations comprising ~60.44 M SNPs, ~6.86 M indels, 76,634 CNV regions, and signatures of selective sweeps in 432 samples from modern cattle worldwide. Users can quickly retrieve distribution patterns of these variations for 54 cattle breeds through an interactive source of breed origin map, using a given gene symbol or genomic region for any of the three versions of the bovine reference genomes (ARS-UCD1.2, UMD3.1.1, and Btau 5.0.1). Signals of selection sweep are displayed as Manhattan plots and Genome Browser tracks. To further investigate and visualize the relationships between variants and signatures of selection, the Genome Browser integrates all variations, selection data, and resources, from NCBI, the UCSC Genome Browser, and Animal QTLdb. Collectively, all these features make the BGVD a useful archive for in-depth data mining and analyses of cattle biology and cattle breeding on a global scale. BGVD is publicly available at http://animal.nwsuaf.edu.cn/BosVar.
Effects of Sterilization With Hydrogen Peroxide and Chlorine Dioxide Solution on the Filtration Efficiency of N95, KN95, and Surgical Face Masks
Authors: Changjie Cai, Evan L. Floyd
Journal: JAMA Network Open (2020)

This quality improvement study examines the effects of sterilization with hydrogen peroxide and chlorine dioxide on the filtration efficiency of N95, KN95, and surgical face masks.
Abstract P313: Dog Walking is Associated With Increased Home-based Exercise in Patients with Coronary Heart Disease
Authors: Susan L Dunn, Michael J Sit, Holli A DeVon, Devynn Makidon, Nathan L Tintle
Journal: Circulation (2017)

Introduction: Dog ownership and dog walking have been associated with increased physical activity in the general population. Although evidence suggests an association between pet ownership and increased survival in patients with coronary heart disease (CHD), little is known about how dog ownership and dog walking may be associated with exercise habits in CHD patients. Hypothesis: The purpose of this study was to examine dog ownership and dog walking and their relationship with frequency of home- and hospital-based CR exercise in patients with CHD. It was hypothesized that CHD patients who walk their dogs would report more frequent home- and hospital-based CR exercise. Methods: The study was based on Self-Determination Theory. A prospective observational design was used. A total of 122 patients with CHD completed a dog ownership and walking survey during their hospitalization and were asked to complete the Cardiac Rehabilitation Exercise Participation Tool by mail at 3, 8 and 12 months later. Patients self-selected whether they walked or biked in a home- or hospital-based Phase II CR exercise setting and self-reported number of days per week of exercise in each setting. Results: The sample was predominantly male (n=82; 67.2%) with a mean age of 64.7±9.1 years. Forty-two patients (34.4%) reported owning a dog. There were no differences in participation in home or Phase II CR exercise in dog owners versus non-dog owners (home CR: 57.1% vs. 62.5%, p=0.57 and Phase II CR: 31.0% vs. 32.5%, p=0.86). Among dog owners, 23 (54.8%) reported walking their dog at least 1 day/week. There were no significant differences in Phase II CR exercise among non-dog owners, dog owners who did not dog walk, and those who walked their dogs at least 1 day/week (owners/walkers: 34.8%, owners/non-walkers: 26.3%, non-owners: 32.5%; p=0.83). However, patients who owned but did not walk their dog reported significantly lower levels of home exercise compared to patients who owned and walked their dogs at least 1 day/week (owners/non-walkers: 36.8% vs. owners/walkers: 73.9%, p=0.019) and compared to non-dog owners (owners/non-walkers: 36.8% vs. non-owners: 62.5%; p=0.047). Conclusions: Results suggest that dog ownership is not equivalent to dog walking when examining exercise frequency in CHD patients. Dog owners were no more likely to exercise than non-dog owners. However, findings show a beneficial effect on home-based exercise for CHD patients who walk their dogs at least one day a week. Healthcare professionals should encourage CHD patients who are dog owners to walk their dogs as a strategy to increase home-based exercise.
Prevalence and characterization of asthma in hospitalized and nonhospitalized patients with COVID-19
Authors: Krishan D. Chhiba, Gayatri B. Patel, Thanh Huyen T. Vu, Michael M. Chen, Amina Guo, Elizabeth Kudlaty, Quan Mai, Chen Yeh, Lutfiyya N. Muhammad, Kathleen E. Harris, Bruce S. Bochner, Leslie C. Grammer, Paul A. Greenberger, Ravi Kalhan, Fei Li Kuang, Carol A. Saltoun, Robert P. Schleimer, Whitney W. Stevens, Anju T. Peters
Journal: Journal of Allergy and Clinical Immunology (2020)
Prognostic effect of the new 5-factor modified frailty index in patients undergoing carotid endarterectomy with regional anesthesia – A prospective cohort study
Authors: Leonardo Araújo-Andrade, João P. Rocha-Neves, Luís Duarte-Gamas, António Pereira-Neves, Hugo Ribeiro, Juliana Pereira-Macedo, Marina Dias-Neto, José Teixeira, José P. Andrade
Journal: International Journal of Surgery (2020)
Nocturnal Blood Pressure Is Associated With Cerebral Small-Vessel Disease in Type 1 Diabetes
Authors: Marika I. Eriksson, Daniel Gordin, Sara Shams, Carol Forsblom, Paula Summanen, Ron Liebkind, Turgut Tatlisumak, Jukka Putaala, Per-Henrik Groop, Juha Martola, Lena M. Thorn
Journal: Diabetes Care (2020)

Although vascular complications are a hallmark of diabetes, cerebral small-vessel disease (cSVD) in type 1 diabetes remains scarcely studied. We recently showed that cSVD is more common in individuals with type 1 diabetes than healthy control subjects and is associated with systolic office blood pressure (BP) (1). Hence, we aimed to further evaluate the impact of BP on cSVD in type 1 diabetes.

This substudy of the Finnish Diabetic Nephropathy (FinnDiane) Study aims to assess early markers of cerebrovascular disease in people with type 1 diabetes and has previously been described in detail (1). Of the 191 neurologically asymptomatic study participants, 73 volunteered for a 24-h ambulatory BP monitoring (ABPM). All participants underwent a clinical study visit, and brain MRI assessed for markers of cSVD (white matter hyperintensities, lacunar infarcts, and cerebral microbleeds) (1,2).

The 24-h ABPM was conducted in accordance with current standards (3). After ABPM-quality validation, we calculated average BP, mean arterial pressure (two-thirds of diastolic + one-third of systolic BP), pulse pressure (PP) (systolic − diastolic BP), BP variability (average real variability), and nocturnal dipping ([1 − nocturnal systolic / diurnal systolic BP] × 100%). Elevated BP and masked hypertension were defined as described by the European Society of Hypertension (3).

We observed cSVD in 20 (27.4%) participants, of whom 14 had cerebral microbleeds, 9 white matter hyperintensities, and 2 lacunes. Table 1 includes clinical characteristics as well as main results for BP measurements based on presence or absence …
Unbiased Proteomic Profiling Uncovers a Targetable GNAS/PKA/PP2A Axis in Small Cell Lung Cancer Stem Cells
Authors: Garry L. Coles, Sandra Cristea, James T. Webber, Rebecca S. Levin, Steven M. Moss, Andy He, Jaya Sangodkar, Yeonjoo C. Hwang, Julia Arand, Alexandros P. Drainas, Nancie A. Mooney, Janos Demeter, Jessica N. Spradlin, Brandon Mauch, Vicky Le, Yan Ting Shue, Julie H. Ko, Myung Chang Lee, Christina Kong, Daniel K. Nomura, Michael Ohlmeyer, Danielle L. Swaney, Nevan J. Krogan, Peter K. Jackson, Goutham Narla, John D. Gordan, Kevan M. Shokat, Julien Sage
Journal: Cancer Cell (2020)
AB1049 CLINICAL SPECTRUM AND THERAPEUTIC MANAGEMENT OF AUTO-IMMUNE MYELOFIBROSIS: A NATION-WIDE STUDY OF 30 CASES
Authors: P. Mertz, E. Chalayer, J. Sibilia, J. E. Gottenberg, A. S. Korganow, L. Arnaud, T. Martin
Journal: Annals of the Rheumatic Diseases (2020)

Background: Little is known about autoimmune myelofibrosis (AIMF), a rare entity that can occur alone or in association with another autoimmune disease (AID) and is responsible for bone marrow (BM) failure and life-threatening complications. Objectives: We conducted a nationwide retrospective observational study of AIMF cases to better characterize the epidemiology, clinical presentation and evolution of this rare entity. Methods: The aim of the study was to analyze the characteristics of AIMF and the nature and indication of treatments currently used. Response to treatment was evaluated by the revised Tefferi et al. response criteria. Results: Among 30 cases of AIMF, the sex ratio (F/M) was 4:1 and the median age at diagnosis was 37 years (interquartile range 30–49). AIMF was diagnosed after the onset of an associated AID in 12 cases and concomitant to an AID in the remaining 18 cases. The most frequently associated AID was systemic lupus erythematous, followed by Sjögren syndrome. All cases consisted of reticulin fibers, and no collagen fibrosis was described. More than 50% of cases showed complete response after first-line therapy, with glucocorticoids (GC) in 28 cases. Half of the cases had treatment complications mainly related to GC therapy. Conclusion: Diagnosis of AIMF remains challenging in the absence of a validated set of diagnosis criteria, and must always be searched in the presence of hematological abnormalities at onset or during follow-up of AID. Clinical context, search for mutations and pathology findings can help differentiating this rare disease from a clonal pathology. GC is currently an effective first-choice therapy for AIMF, but a high rate of GC dependency and long-term complications indicate the need to find new sparing drugs. Disclosure of Interests: PHILIPPE MERTZ: None declared, Emilie Chalayer: None declared, Jean Sibilia: None declared, Jacques-Eric Gottenberg Grant/research support from: BMS, Pfizer, Consultant of: BMS, Sanofi-Genzyme, UCB, Speakers bureau: Abbvie, Eli Lilly and Co., Roche, Sanofi-Genzyme, UCB, Anne-Sophie Korganow: None declared, Laurent Arnaud: None declared, Thierry Martin: None declared
Long-Term Follow-Up of the First in Human Intravascular Delivery of AAV for Gene Transfer: AAV2-hFIX16 for Severe Hemophilia B
Authors: Lindsey A. George, Margaret V. Ragni, John E.J. Rasko, Leslie J. Raffini, Benjamin J. Samelson-Jones, Margareth Ozelo, Maria Hazbon, Alexa R. Runowski, Jennifer A. Wellman, Katie Wachtel, Yifeng Chen, Xavier M. Anguela, Klaudia Kuranda, Federico Mingozzi, Katherine A. High
Journal: Molecular Therapy (2020)

Adeno-associated virus (AAV) vectors are a leading platform for gene-based therapies for both monogenic and complex acquired disorders. The success of AAV gene transfer highlights the need to answer outstanding clinical questions of safety, durability, and the nature of the human immune response to AAV vectors. Here, we present longitudinal follow-up data of subjects who participated in the first trial of a systemically delivered AAV vector. Adult males (n = 7) with severe hemophilia B received an AAV2 vector at doses ranging from 8 × 1010 to 2 × 1012 vg/kg to target hepatocyte-specific expression of coagulation factor IX; a subset (n = 4) was followed for 12-15 years post-vector administration. No major safety concerns were observed. There was no evidence of sustained hepatic toxicity or development of hepatocellular carcinoma as assessed by liver transaminase values, serum α-fetoprotein, and liver ultrasound. Subjects demonstrated persistent, increased AAV neutralizing antibodies (NAbs) to the infused AAV serotype 2 (AAV2) as well as all other AAV serotypes tested (AAV5 and AAV8) for the duration of follow-up. These data represent the longest available longitudinal follow-up data of subjects who received intravascular AAV and support the preliminary safety of intravascular AAV administration at the doses tested in adults. Data demonstrate, for the first time, the persistence of high-titer, multi-serotype cross-reactive AAV NAbs for up to 15 years post- AAV vector administration. Our observations are broadly applicable to the development of AAV-mediated gene therapy.
The Current Health Care Crisis—Inspirational Leadership (or Lack Thereof) Is Contagious
Authors: F. Bruder Stapleton, Valerie P. Opipari
Journal: JAMA Network Open (2020)

Tait D. Shanafelt, MD; Maryam S. Makowski, PhD; Hanhan Wang, MPS; Bryan Bohman, MD; Mary Leonard, MD; Robert A. Harrington, MD; Lloyd Minor, MD; Mickey Trockel, MD, PhD