tbuckley/cabot-search huggingface dataset:
Calcium/Calmodulin-Dependent Protein Kinase II Delta Inhibition and Ventricular Remodeling After Myocardial Infarction
Authors: Andrew J. Boyle, Carl Schultz, Joseph B. Selvanayagam, Stuart Moir, Richard Kovacs, Nabil Dib, David Zlotnick, Mohammed Al-Omary, Stuart Sugito, Aravinda Selvarajah, Nicholas Collins, Grant McLachlan
Journal: JAMA Cardiology (2021)

After anterior ST-segment elevation myocardial infarction (STEMI), left ventricular (LV) remodeling results in heart failure and death. Calcium/calmodulin-dependent protein kinase II delta (CaMKIId) is a key molecular mediator of adverse LV remodeling.To determine whether NP202, an orally active inhibitor of CaMKIId, prevents LV remodeling in patients after anterior STEMI with early residual LV dysfunction.A randomized, double-blind, placebo-controlled multicenter clinical trial of NP202 vs placebo in patients after primary percutaneous coronary intervention (PCI) for anterior STEMI was performed from November 19, 2015, to August 1, 2018. The study was performed at 32 sites across the US, Australia, and New Zealand. Patients presenting with anterior STEMI who underwent PCI within 12 hours of symptom onset and left ventricular ejection fraction (LVEF) less than 45% on screening echocardiogram 48 hours after primary PCI were included in the study. Baseline cardiovascular magnetic resonance (CMR) imaging was performed within 5 days of the STEMI and before administration of the study drug. Follow-up CMR was performed after 3 months. Data were analyzed from November 19, 2015, to August 1, 2018.Patients were randomly assigned to NP202, 1000 mg, daily for 3 months vs corresponding placebo.The primary end point was change in LV end-systolic volume index (LVESVi) on CMR. Secondary end points were change in LV end-diastolic volume index, change in LVEF, change in infarct size, and change in diastolic function. Safety and tolerability were also assessed.A total of 147 patients (mean [SD] age, 58 [11] years; 129 men [88%]; 130 White patients [88%]) who experienced anterior STEMI treated with primary PCI were randomized to receive NP202 (73 [49.7%]) or placebo (74 [50.3%]). Baseline LVEF was similar between groups. At baseline, patients randomized to NP202 had greater LVESVi (48.2 mL/m2) than that in the placebo group (41.3 mL/m2; P = .03). However, the groups were otherwise well matched. For the primary end point of change in LVESVi from baseline to 3 months, there was no significant difference between the placebo (median [interquartile range] change, -0.60 [-9.28 to 5.99] mL/m2) and NP202 groups (-3.53 [-9.24 to 4.81] mL/m2) (P = .78). There was also no difference in the secondary efficacy end points assessed by CMR. NP202 was well tolerated and demonstrated an acceptable safety profile. Major adverse cardiac and cerebrovascular event rates were similar between groups. Two deaths occurred in each group during the follow-up period.Three months of treatment with NP202 after primary PCI for anterior STEMI with residual LV dysfunction did not improve LV remodeling. The drug was safe and well tolerated.ClinicalTrials.gov Identifier: NCT02557217.
1818P Body mass index (BMI) is not a cancer risk factor for BRCA1/2 carriers: A systematic review and meta-analysis of case-control studies
Authors: V. Gristina, A. Galvano, M. Mirisola, M. La Mantia, M. Giaconia, F. Li Pomi, N. Barraco, M. Castiglia, A. Perez, M. Bono, F. Iacono, S. Cutaia, M.C. Lisanti, L. Insalaco, L. Castellana, V. Calò, S. Cusenza, L. Incorvaia, A. Russo, V. Bazan
Journal: Annals of Oncology (2021)
Abstract 12855: The Long-Term Effects of Inferior Vena Cava Filter Placement for Cancer-Associated Venous Thromboembolism
Authors: Toru Takase, Yoshitaka Iwanaga, Yugo Yamashita, Kousuke Fujita, Heitaro Watanabe, Kenji Yamaji, Ryobun Yasuoka, Masafumi Ueno, Kazuhiro Kobuke, Hidewo Amano, Seiichi Hiramori, Kitae Kim, Togi Kiyonori, Takeshi Kimura, Shunichi Miyazaki
Journal: Circulation (2018)

Background: The effectiveness of inferior vena cava (IVC) filters for the cancer-associated venous thromboembolism (VTE) is unclear. Purpose: The aim of this study was to evaluate the relationship ...
Molecular Subtypes of Pancreatic Cancer: A Proteomics Approach
Authors: Ravi Thakur, Pankaj K. Singh
Journal: Clinical Cancer Research (2021)

Through molecular subtyping, therapeutic vulnerabilities can be exploited for developing personalized medicine. The real utility of molecular subtyping lies in the clinical translation for disease characterization. Proteomic methods with defined marker sets hold great promise for improving therapy outcomes by improving the speed of predictions for devising treatment strategies.See related article by Son et al., p. 3370.
The shared susceptibility epitope of HLA-DR4 binds citrullinated self-antigens and the TCR
Authors: Jia Jia Lim, Claerwen M. Jones, Tiing Jen Loh, Yi Tian Ting, Pirooz Zareie, Khai L. Loh, Nathan J. Felix, Anish Suri, Murray McKinnon, Frederik Stevenaert, Ravi K. Sharma, Lars Klareskog, Vivianne Malmström, Daniel G. Baker, Anthony W. Purcell, Hugh H. Reid, Nicole L. La Gruta, Jamie Rossjohn
Journal: Science Immunology (2021)

Citrullination of a fibrinogen peptide influences HLA-DR4 binding and TCR usage by neoepitope-reactive T cells in rheumatoid arthritis.
Performance of a digital signal processing algorithm for the accurate quantification of cough frequency
Authors: Jaclyn A. Smith, Kimberley Holt, Rachel Dockry, Shilpi Sen, Kitty Sheppard, Philip Turner, Paul Czyzyk, Kevin McGuinness
Journal: European Respiratory Journal (2021)

<b>The VitaloJAK filtering algorithm has undergone the most extensive testing of any cough monitoring software and is sensitive/efficient across a range of diagnoses and age groups, and in recordings containing a wide range of cough counts</b>https://bit.ly/3rF9vp1
Nuclear mechanosensing drives chromatin remodelling in persistently activated fibroblasts
Authors: Cierra J. Walker, Claudia Crocini, Daniel Ramirez, Anouk R. Killaars, Joseph C. Grim, Brian A. Aguado, Kyle Clark, Mary A. Allen, Robin D. Dowell, Leslie A. Leinwand, Kristi S. Anseth
Journal: Nature Biomedical Engineering (2021)
Performance characteristics of five antigen-detecting rapid diagnostic test (Ag-RDT) for SARS-CoV-2 asymptomatic infection: a head-to-head benchmark comparison
Authors: Bàrbara Baro, Pau Rodo, Dan Ouchi, Antoni E. Bordoy, Emilio N. Saya Amaro, Sergi V. Salsench, Sònia Molinos, Andrea Alemany, Maria Ubals, Marc Corbacho-Monné, Pere Millat-Martinez, Michael Marks, Bonaventura Clotet, Nuria Prat, Oriol Estrada, Marc Vilar, Jordi Ara, Martí Vall-Mayans, Camila G-Beiras, Quique Bassat, Ignacio Blanco, Oriol Mitjà
Journal: Journal of Infection (2021)
Glucagon-Like Peptide 1 Receptor Agonists and Chronic Lower Respiratory Disease Exacerbations Among Patients With Type 2 Diabetes
Authors: Yasser Albogami, Kenneth Cusi, Michael J. Daniels, Yu-Jung J. Wei, Almut G. Winterstein
Journal: Diabetes Care (2021)

Emerging data from animal and human pilot studies suggest potential benefits of glucagon-like peptide 1 receptor agonists (GLP-1RA) on lung function. We aimed to assess the association of GLP-1RA and chronic lower respiratory disease (CLRD) exacerbation in a population with comorbid type 2 diabetes (T2D) and CLRD.A new-user active-comparator analysis was conducted with use of a national claims database of beneficiaries with employer-sponsored health insurance spanning 2005-2017. We included adults with T2D and CLRD who initiated GLP-1RA or dipeptidyl peptidase 4 inhibitors (DPP-4I) as an add-on therapy to their antidiabetes regimen. The primary outcome was time to first hospital admission for CLRD. The secondary outcome was a count of any CLRD exacerbation associated with an inpatient or outpatient visit. We estimated incidence rates using inverse probability of treatment weighting for each study group and compared via risk ratios.The study sample consisted of 4,150 GLP-1RA and 12,540 DPP-4I new users with comorbid T2D and CLRD. The adjusted incidence rate of first CLRD admission during follow-up was 10.7 and 20.3 per 1,000 person-years for GLP-1RA and DPP-4I users, respectively, resulting in an adjusted hazard ratio of 0.52 (95% CI 0.32-0.85). For the secondary outcome, the adjusted incidence rate ratio was 0.70 (95% CI 0.57-0.87).GLP-1RA users had fewer CLRD exacerbations in comparison with DPP-4I users. Considering both plausible mechanistic pathways and this real-world evidence, potential beneficial effects of GLP-1RA may be considered in selection of an antidiabetes treatment regimen. Randomized clinical trials are warranted to confirm our findings.
Association of Epidural Labor Analgesia With Offspring Risk of Autism Spectrum Disorders
Authors: Elizabeth Wall-Wieler, Brian T. Bateman, Ana Hanlon-Dearman, Leslie L. Roos, Alexander J. Butwick
Journal: JAMA Pediatrics (2021)

<h3>Importance</h3> Epidural labor analgesia (ELA) has been associated with an increased offspring risk of autism spectrum disorder (ASD). Whether this finding may be explained by residual confounding remains unclear. <h3>Objective</h3> To assess the association between ELA and offspring risk of ASD. <h3>Design, Setting, and Participants</h3> Longitudinal cohort study of vaginal deliveries of singleton live infants born from 2005 to 2016 from a population-based data set linking information from health care databases in Manitoba, Canada; offspring were followed from birth until 2019 or censored by death or emigration. Data were analyzed from October 19, 2020, to January 22, 2021. <h3>Exposures</h3> Epidural labor analgesia. <h3>Main Outcomes and Measures</h3> At least 1 inpatient or outpatient diagnosis of ASD in offspring aged at least 18 months. For the full population and a sibling cohort, inverse probability of treatment-weighted Cox proportional hazards regression analyses were used to control for potential confounders. <h3>Results</h3> Of the 123 175 offspring included in this study (62 647 boys [50.9%]; mean [SD] age of mothers, 28.2 [5.8] years), 47 011 (38.2%) were exposed to ELA; 2.1% (985 of 47 011) of exposed vs 1.7% (1272 of 76 164) of unexposed offspring were diagnosed with ASD in the follow-up period (hazard ratio [HR], 1.25; 95% CI, 1.15-1.36). After adjusting for maternal sociodemographic, prepregnancy, pregnancy, and perinatal covariates, ELA was not associated with an offspring risk of ASD (inverse probability of treatment–weighted HR, 1.08; 95% CI, 0.97-1.20). In the within-siblings design adjusting for baseline covariates, ELA was not associated with ASD (inverse probability of treatment–weighted HR, 0.97; 95% CI, 0.78-1.22). Results from sensitivity analyses restricted to women without missing data who delivered at or after 37 weeks of gestation, firstborn infants only, and offspring with ASD classified with at least 2 diagnostic codes were consistent with findings from the main analyses. <h3>Conclusions and Relevance</h3> In a Canadian population-based birth cohort study, no association between ELA exposure and an increased offspring risk of ASD was found.
Abstract 18695: Elevated Intracellular Adenosine Induces Placental DNA Hypomethylation and Contributes to Pathophysiology of Preeclampsia
Authors: Aji Huang, Hongyu Wu, Takayuki Iriyama, Kaiqi Sun, Anren Song, Hong Liu, Zhangzhe Peng, Lili Tang, Rodney Kellems, Yang Xia
Journal: Circulation (2017)

Preeclampsia (PE) is a prevalent pregnancy hypertensive disease with both maternal and fetal morbidity and mortality. Previous studies indicate that elevated extracellular placental adenosine (Ado)...
Quantification of HER2 degradation following 17-DMAG treatment by PET imaging
Authors: Gabriela Kramer-Marek, Dale O. Kiesewetter, Yesenia Rodriguez, Jacek Capala
Journal: Cancer Research (2008)

3179  HER2 overexpression is an independent prognostic indicator of poor long-term survival in patients with breast cancer. In vivo imaging of HER2 expression could allow a direct and global assessment of HER2 status of primary and metastatic lesions, thereby, providing means for improved diagnosis and selection of patients for HER2-targeted therapies. It could be also used to monitor and quantify possible changes in receptor expression following such therapies.  This work describes in vivo characterization of a novel HER2-specific 18F-ZHER2-Affibodymolecule and its application to study the effect of 17-DMAG on HER2 expression in tumor xenografts by PET imaging. We have applied maleimide chemistry to attach the positron emitting radionuclide, 18F, to ZHER2-Cys Affibody molecule - a very stable protein of relatively low molecular weight (8.3 kDa) that binds to HER2 with high affinity. To assess the correlation of signal observed by PET with receptor expression, we administered the new tracer to athymic nude mice bearing subcutaneous tumors with three different levels of HER2 expression: 1. BT-474 (very high), 2. Mcf-7/clone18 (high), and 3. Mcf7 (very low).  Our results showed that 18F-ZHER2-Affibody was eliminated quickly from the blood and normal tissues, providing high tumor/blood and tumor/muscle ratios as soon as 1 h post injection. The high contrast images between normal and tumor tissue were recorded for BT-474 and Mcf7/clone18 tumors. Very low but still detectable uptake was observed for Mcf7 tumors. The signal correlated very well with the number of receptors expressed in those particular cell lines. Two hours post injection, PET ROI analysis indicated tumor/muscle ratio as high as 22, which was sufficient to obtain high contrast images even at earlier time points. Biodistribution data showed that the tumor uptake was higher than uptake in any other organ at that time.  To study the down-regulation of HER2 in human breast cancer xenografts, the mice were treated with two doses (30-50 mg/kg, 12 or 24 h apart) of 17-DMAG, an inhibitor of Hsp90 known to decrease the HER2 expression. Animals (n = 4-6) were scanned before, 36h, and 84h after the treatment. Immediately after the last scan, animals were euthanized and tumors were frozen for further analysis. Then HER-2 expression was measured by western blot, ELISA, and MSD biomarker detection assays. In animals treated with 17-DMAG the level of HER2 expression estimated by PET imaging decreased 50-60% at 84h post-treatment. This change was confirmed by the biodistribution studies.  Our results suggest that the described 18F-ZHER2-Affibody radioconjugate can be used to assess HER2 expression in vivo by PET imaging providing means to monitor possible changes of receptor expression in response to therapeutic interventions.
Perceptual Inference, Learning, and Attention in a Multisensory World
Authors: Uta Noppeney
Journal: Annual Review of Neuroscience (2021)

Adaptive behavior in a complex, dynamic, and multisensory world poses some of the most fundamental computational challenges for the brain, notably inference, decision-making, learning, binding, and attention. We first discuss how the brain integrates sensory signals from the same source to support perceptual inference and decision-making by weighting them according to their momentary sensory uncertainties. We then show how observers solve the binding or causal inference problem-deciding whether signals come from common causes and should hence be integrated or else be treated independently. Next, we describe the multifarious interplay between multisensory processing and attention. We argue that attentional mechanisms are crucial to compute approximate solutions to the binding problem in naturalistic environments when complex time-varying signals arise from myriad causes. Finally, we review how the brain dynamically adapts multisensory processing to a changing world across multiple timescales.
The coexistence of asthma and COPD: risk factors, clinical history and lung function trajectories
Authors: Alessandro Marcon, Francesca Locatelli, Shyamali C. Dharmage, Cecilie Svanes, Joachim Heinrich, Bénédicte Leynaert, Peter Burney, Angelo Corsico, Gulser Caliskan, Lucia Calciano, Thorarinn Gislason, Christer Janson, Deborah Jarvis, Rain Jõgi, Theodore Lytras, Andrei Malinovschi, Nicole Probst-Hensch, Kjell Toren, Lidia Casas, Giuseppe Verlato, Judith Garcia-Aymerich, Simone Accordini
Journal: European Respiratory Journal (2021)

Patients with concomitant features of asthma and chronic obstructive pulmonary disease (COPD) have a heavy disease burden.Using data collected prospectively in the European Community Respiratory Health Survey, we compared the risk factors, clinical history and lung function trajectories from early adulthood to late sixties of middle-aged subjects with asthma+COPD (n=179), past (n=263) or current (n=808) asthma alone, COPD alone (n=111) or none of these (n=3477).Interview data and pre-bronchodilator forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were obtained during three clinical examinations in 1991-1993, 1999-2002 and 2010-2013. Disease status was classified in 2010-2013, when the subjects were aged 40-68 years, according to the presence of fixed airflow obstruction (post-bronchodilator FEV1/FVC below the lower limit of normal), a lifetime history of asthma and cumulative exposure to tobacco or occupational inhalants. Previous lung function trajectories, clinical characteristics and risk factors of these phenotypes were estimated.Subjects with asthma+COPD reported maternal smoking (28.2%) and respiratory infections in childhood (19.1%) more frequently than subjects with COPD alone (20.9% and 14.0%, respectively). Subjects with asthma+COPD had an impairment of lung function at age 20 years that tracked over adulthood, and more than half of them had asthma onset in childhood. Subjects with COPD alone had the highest lifelong exposure to tobacco smoking and occupational inhalants, and they showed accelerated lung function decline during adult life.The coexistence between asthma and COPD seems to have its origins earlier in life compared to COPD alone. These findings suggest that prevention of this severe condition, which is typical at older ages, should start in childhood.
Radiologic-Pathologic Correlation of Liver Tumors
Authors: Eric Lachance, Jake Mandziuk, Consolato M. Sergi, Justin Bateman, Gavin Low
Journal: Liver Cancer (2021)

Radiologic and pathologic features of common and/or critical tumor or tumor-like diagnoses (lesions) of the liver are discussed within. Hepatocellular lesions (focal nodular hyperplasia, hepatocellular adenoma, hepatocellular carcinoma, and hepatoblastoma), biliary lesions (mucinous cystic neoplasm and intrahepatic cholangiocarcinoma), vascular mesenchymal lesions (cavernous hemangioma, epithelioid hemangioendothelioma, and hepatic angiosarcoma), and metastatic malignancies are the primary focus, although a more comprehensive list of lesions is also provided. Definitions, distributions, gross appearances and microscopic pathological features are introduced first, followed by radiologic correlation. Multiple imaging modalities are explored with an emphasis on those that provide the greatest value for the lesion under evaluation. A common understanding of the features of both diagnostic specialties will allow for high-quality correlation and subsequent high-quality patient care. Representative images highlighting important features are also presented.
ICON3 and chemotherapy for ovarian cancer [14] (multiple letters)
Authors: Robert F. Ozols, Maurie Markman, J. Tate Thigpen, Helena Earl, Silvana Pilotti, Maria Oggionni, Silvia Böhm, Marco A. Pierotti, Franco Zunino, Mahesh Parmar, Peter Harper, Nicoletta Colombo, Valter Torri, David Guthrie
Journal: The Lancet (2002)
Fibrotic extracellular matrix induces release of extracellular vesicles with pro-fibrotic miRNA from fibrocytes
Authors: Seidai Sato, Sy Giin Chong, Chandak Upagupta, Toyoshi Yanagihara, Takuya Saito, Chiko Shimbori, Pierre-Simon Bellaye, Yasuhiko Nishioka, Martin RJ Kolb
Journal: Thorax (2021)

Rationale Extracellular vesicles (EVs) are small lipid vesicles, and EV-coupled microRNAs (miRNAs) are important modulators of biological processes. Fibrocytes are circulating bone marrow-derived cells that migrate into the injured lungs and contribute to fibrogenesis. The question of whether EV-coupled miRNAs derived from fibrocytes are able to regulate pulmonary fibrosis has not been addressed yet. Methods Pulmonary fibrosis was induced in rats by intratracheal administration of an adenoviral gene vector encoding active transforming growth factor-β1 (TGF-β1) or control vector. Primary fibrocytes and fibroblasts were cultured from rat lungs and were sorted by anti-CD45 magnetic beads. Human circulating fibrocytes and fibrocytes in bronchoalveolar lavage fluid (BALF) were isolated by fibronectin-coated dishes. Fibrocytes were cultured on different stiffness plates or decellularised lung scaffolds. We also determined the effects of extracellular matrix (ECM) and recombinant TGF-β1 on the cellular and EV-coupled miRNA expression of fibrocytes. Results The EVs of fibrocytes derived from fibrotic lungs significantly upregulated the expression of col1a1 of fibroblasts. Culturing on rigid plates or fibrotic decellularised lung scaffolds increased miR-21-5 p expression compared with soft plates or normal lung scaffolds. Dissolved ECM collected from fibrotic lungs and recombinant TGF-β1 increased miR-21-5 p expression on fibrocytes, and these effects were attenuated on soft plates. Fibrocytes from BALF collected from fibrotic interstitial pneumonia patients showed higher miR-21-5 p expression than those from other patients. Conclusions Our results indicate that ECM contributes to fibrogenesis through biomechanical and biochemical effects on miRNA expression in fibrocytes.
Abstract 15182: Imaging iPSC-Derived Cardiomyocytes Engrafted in a Mouse Model of Myocardial Infarction Using Stably Expressed APEX2
Authors: Takeshi Hatani, Shunsuke Funakoshi, Thomas J Deerinck, Eric A Bushong, Takeshi Kimura, Shinya Yamanaka, Mark H Ellisman, Masahiko Hoshijima, Yoshinori Yoshida
Journal: Circulation (2017)

Background: Although studies have shown the promising results for in vivo cardiac transplantation of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) in animal experiments, nan...
Conservation of Aging and Cancer Epigenetic Signatures across Human and Mouse
Authors: Raúl F Pérez, Juan Ramón Tejedor, Pablo Santamarina-Ojeda, Virginia López Martínez, Rocío G Urdinguio, Lucía Villamañán, Ana Paula Candiota, Noemí Vidal Sarró, Marta Barradas, Pablo Jose Fernandez-Marcos, Manuel Serrano, Agustín F Fernández, Mario F Fraga
Journal: Molecular Biology and Evolution (2021)

Aging and cancer are two interrelated processes, with aging being a major risk factor for the development of cancer. Parallel epigenetic alterations have been described for both, although differences, especially within the DNA hypomethylation scenario, have also been recently reported. Although many of these observations arise from the use of mouse models, there is a lack of systematic comparisons of human and mouse epigenetic patterns in the context of disease. However, such comparisons are significant as they allow to establish the extent to which some of the observed similarities or differences arise from pre-existing species-specific epigenetic traits. Here, we have used reduced representation bisulfite sequencing to profile the brain methylomes of young and old, tumoral and nontumoral brain samples from human and mouse. We first characterized the baseline epigenomic patterns of the species and subsequently focused on the DNA methylation alterations associated with cancer and aging. Next, we described the functional genomic and epigenomic context associated with the alterations, and finally, we integrated our data to study interspecies DNA methylation levels at orthologous CpG sites. Globally, we found considerable differences between the characteristics of DNA methylation alterations in cancer and aging in both species. Moreover, we describe robust evidence for the conservation of the specific cancer and aging epigenomic signatures in human and mouse. Our observations point toward the preservation of the functional consequences of these alterations at multiple levels of genomic regulation. Finally, our analyses reveal a role for the genomic context in explaining disease- and species-specific epigenetic traits.