tbuckley/cabot-search huggingface dataset:
Association Between Cardiovascular Disease and Long-term Exposure to Air Pollution With the Risk of Dementia
Authors: Giulia Grande, Petter L. S. Ljungman, Kristina Eneroth, Tom Bellander, Debora Rizzuto
Journal: JAMA Neurology (2020)

Emerging yet contrasting evidence associates air pollution with incident dementia, and the potential role of cardiovascular disease (CVD) in this association is unclear.To investigate the association between long-term exposure to air pollution and dementia and to assess the role of CVD in that association.Data for this cohort study were extracted from the ongoing Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), a longitudinal population-based study with baseline assessments from March 21, 2001, through August 30, 2004. Of the 5111 randomly selected residents in the Kungsholmen district of Stockholm 60 years or older and living at home or in institutions, 521 were not eligible (eg, due to death before the start of the study or no contact information). Among the remaining 4590 individuals, 3363 (73.3%) were assessed. For the current analysis, 2927 participants who did not have dementia at baseline were examined, with follow-up to 2013 (mean [SD] follow-up time, 6.01 [2.56] years). Follow-up was completed February 18, 2013, and data were analyzed from June 26, 2018, through June 20, 2019.Two major air pollutants (particulate matter ≤2.5 μm [PM2.5] and nitrogen oxide [NOx]) were assessed yearly from 1990, using dispersion models for outdoor levels at residential addresses.The hazard of dementia was estimated using Cox proportional hazards regression models. The potential of CVD (ie, atrial fibrillation, ischemic heart disease, heart failure, and stroke) to modify and mediate the association between long-term exposure to air pollution and dementia was tested using stratified analyses and generalized structural equation modeling.At baseline, the mean (SD) age of the 2927 participants was 74.1 (10.7) years, and 1845 (63.0%) were female. Three hundred sixty-four participants with incident dementia were identified. The hazard of dementia increased by as much as 50% per interquartile range difference in mean pollutant levels during the previous 5 years at the residential address (hazard ratio [HR] for difference of 0.88 μg/m3 PM2.5, 1.54 [95% CI, 1.33-1.78]; HR for difference of 8.35 μg/m3 NOx, 1.14 [95% CI, 1.01-1.29]). Heart failure (HR for PM2.5, 1.93 [95% CI, 1.54-2.43]; HR for NOx, 1.43 [95% CI, 1.17-1.75]) and ischemic heart disease (HR for PM2.5, 1.67 [95% CI, 1.32-2.12]; HR for NOx, 1.36 [95% CI, 1.07-1.71]) enhanced the dementia risk, whereas stroke appeared to be the most important intermediate condition, explaining 49.4% of air pollution-related dementia cases.This study found that long-term exposure to air pollution was associated with a higher risk of dementia. Heart failure and ischemic heart disease appeared to enhance the association between air pollution and dementia, whereas stroke seemed to be an important intermediate condition between the association of air pollution exposure with dementia.
Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction
Authors: Paul W. Armstrong, Burkert Pieske, Kevin J. Anstrom, Justin Ezekowitz, Adrian F. Hernandez, Javed Butler, Carolyn S.P. Lam, Piotr Ponikowski, Adriaan A. Voors, Gang Jia, Steven E. McNulty, Mahesh J. Patel, Lothar Roessig, Joerg Koglin, Christopher M. O’Connor
Journal: New England Journal of Medicine (2020)

The effect of vericiguat, a novel oral soluble guanylate cyclase stimulator, in patients with heart failure and reduced ejection fraction who had recently been hospitalized or had received intravenous diuretic therapy is unclear.
Self-palpation for detection of paroxysmal atrial fibrillation: Much noise with little signal
Authors: Kazem Rahimi, Paulus Kirchhof
Journal: PLoS Medicine (2020)

Patients with atrial fibrillation (AF) are at substantially increased risk of various adverse cardiovascular events, such as stroke, myocardial infarction, heart failure, and vascular dementia [1].Given that such risks can be partially mitigated through preventive measures, it is important to understand how to better identify people affected by AF and how better identification might change treatment decisions or outcomes.The cardinal feature of AF is the presence of an irregular pulse.Advocating for pulse palpation might, then, seem a simple and ubiquitously available solution for detecting undiagnosed AF.Indeed, previous research has shown that such a simple screening method, when adopted by trained health professionals, is as good as systematic screening with the use of ECG [2].Hence, systematic pulse palpation is recommended during routine clinical encounters of atrisk patients [3,4].However, although such screening will detect chronic forms of AF when patients are seen by health professionals, it neither detects intermittent, paroxysmal AF nor facilitates the diagnosis of AF in populations not assessed by health professionals.These "holes in the current screening net" might be plugged by regular self-pulse palpations by laypersons.In this context, Faris Ghazal and colleagues compared self-pulse palpation to simultaneously recorded ECGs in an important study reported in PLOS Medicine [5].They recruited around 1,000 individuals aged 65 years and over from 4 primary care centres in Sweden.All participants were trained on how to monitor irregular pulse rhythms 3 times a day over a 2-week period.Importantly, they were also given a handheld ECG device and were advised to record their heart rhythm simultaneously with self-palpation.This resulted in 53,782 simultaneous pulse palpations and ECG recordings (51 recordings per individual).Intermittent ECG recordings were confirmed to be effective in detecting 27 patients with AF (2.7%, 95% CI 1.8-3.9).Only a small minority of recordings (42 patients) required verification with a heart rhythm patch that was worn over 5 days (with AF being verified in just 4 of these patients, i.e., 10%).All but 2 individuals had paroxysmal AF, illustrating the power of patient-operated ECG devices.But how well did self-palpation perform?In short, not very well.Only 15 of the 27 individuals with newly diagnosed AF reported at least 1 episode of irregular pulse during the screening period.This translates to a sensitivity of 56% (95% CI 35%-75%) for diagnosis of AF by selfpalpation at the individual level or 25% (95% CI 20%-30%) at the level of episodes of self-palpation.More importantly, the positive predictive value of self-palpation was disappointingly low (7%, 95% CI 5%-10%).This means that for each correctly detected irregular pulse, there
Autophagy induction by thiostrepton improves the efficacy of immunogenic chemotherapy
Authors: Yan Wang, Wei Xie, Juliette Humeau, Guo Chen, Peng Liu, Jonathan Pol, Zhen Zhang, Oliver Kepp, Guido Kroemer
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Immunogenic cell death (ICD) is a peculiar modality of cellular demise that elicits adaptive immune responses and triggers T cell-dependent immunity. Methods Fluorescent biosensors were employed for an unbiased drug screen approach aiming at the identification of ICD enhancers. Results Here, we discovered thiostrepton as an enhancer of ICD able to boost chemotherapy-induced ATP release, calreticulin exposure and high-mobility group box 1 exodus. Moreover, thiostrepton enhanced anticancer immune responses of oxaliplatin (OXA) in vivo in immunocompetent mice, yet failed to do so in immunodeficient animals. Consistently, thiostrepton combined with OXA altered the ratio of cytotoxic T lymphocytes to regulatory T cells, thus overcoming immunosuppression and reinstating anticancer immunosurveillance. Conclusion Altogether, these results indicate that thiostrepton can be advantageously combined with chemotherapy to enhance anticancer immunogenicity.
β<sub>2</sub>-integrin LFA1 mediates airway damage following neutrophil transepithelial migration during respiratory syncytial virus infection
Authors: Jenny Amanda Herbert, Yu Deng, Pia Hardelid, Elisabeth Robinson, Luo Ren, Dale Moulding, Rosalind Louise Smyth, Claire Mary Smith
Journal: European Respiratory Journal (2020)

Respiratory syncytial virus (RSV) bronchiolitis is the most common cause of infant hospital admissions, but there is limited understanding of the mechanisms of disease, and no specific antiviral treatment. Using a novel in vitro primary transepithelial neutrophil migration model and innovative imaging methods, we show that RSV infection of nasal airway epithelium increased neutrophil transepithelial migration and adhesion to infected epithelial cells, which is associated with epithelial cell damage and reduced ciliary beat frequency, but also with a reduction in infectious viral load. Following migration, RSV infection results in greater neutrophil activation, degranulation and release of neutrophil elastase into the airway surface media compared to neutrophils that migrated across mock-infected nasal epithelial cells. Blocking of the interaction between the ligand on neutrophils (the β 2 -integrin LFA-1) for intracellular adhesion molecule (ICAM)-1 on epithelial cells reduced neutrophil adherence to RSV-infected cells and epithelial cell damage to pre-infection levels, but did not reduce the numbers of neutrophils that migrated or prevent the reduction in infectious viral load. These findings have provided important insights into the contribution of neutrophils to airway damage and viral clearance, which are relevant to the pathophysiology of RSV bronchiolitis. This model is a convenient, quantitative preclinical model that will further elucidate mechanisms that drive disease severity and has utility in antiviral drug discovery.
Effects of Sacubitril/Valsartan on N-Terminal Pro-B-Type Natriuretic Peptide in Heart Failure With Preserved Ejection Fraction
Authors: Jonathan W. Cunningham, Muthiah Vaduganathan, Brian L. Claggett, Michael R. Zile, Inder S. Anand, Milton Packer, Faiez Zannad, Carolyn S.P. Lam, Stefan Janssens, Pardeep S. Jhund, Lars Kober, Jean Rouleau, Sanjiv J. Shah, Vijay K. Chopra, Victor C. Shi, Martin P. Lefkowitz, Margaret F. Prescott, Marc A. Pfeffer, John J.V. McMurray, Scott D. Solomon
Journal: JACC Heart Failure (2020)

The authors sought to evaluate the prognostic significance of baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP), whether NT-proBNP modified the treatment response to sacubitril/valsartan, and the treatment effect of sacubitril/valsartan on NT-proBNP overall and in key subgroups.
Strategic plan for management of COVID-19 in paediatric haematology and oncology departments
Authors: Yulei He, Zhi Lin, Daolin Tang, Yang Yang, Tianyou Wang, Minghua Yang
Journal: The Lancet Haematology (2020)

can improve survival in patients with multiple myeloma.Results from most phase 3 trials are pending, and the optimal sequencing of the different treatments is unknown.In the meantime, before assigning treatment for a patient with multiple myeloma, clinicians should consider the features of the disease and the profile of the patient.
Rosai-Dorfman Disease Presenting as a Pulmonary Artery Mass on FDG PET/CT
Authors: Guozhu Hou, Kailin Chen, Yuanyuan Jiang, Wuying Cheng, Fang Li
Journal: Clinical Nuclear Medicine (2020)

Abstract Rosai-Dorfman disease (RDD) is an uncommon histiocytic disorder typically involving the lymph nodes and occasionally manifests as extranodal disease. Extranodal RDD involving pulmonary artery without lymphadenopathy or other extranodal lesions is very rare. We present the case of a 48-year-old woman complaining of shortness of breath on exertion for 6 months. 18 F-FDG PET/CT revealed a pulmonary artery mass with intense FDG avidity. No other abnormal FDG-avid lesion was observed. The pulmonary artery mass was then surgically removed, and the pathological and immunohistochemical results confirmed RDD.
FAM19A4/miR124-2 methylation analysis as a triage test for HPV-positive women: cross-sectional and longitudinal data from a Dutch screening cohort
Authors: F.J. Vink, B.I. Lissenberg-Witte, C.J.L.M. Meijer, J. Berkhof, F.J. van Kemenade, A.G. Siebers, R.D.M. Steenbergen, M.C.G. Bleeker, D.A.M. Heideman
Journal: Clinical Microbiology and Infection (2020)
Abstract P3-10-13: Rac inhibition as an alternative approach to treating hormone dependent breast cancer
Authors: Erik T Goka, Jun Sun, Dayrelis T Mesa Lopez, Marc E Lippman
Journal: Cancer Research (2020)

Abstract Hormone positive breast cancer remains one of the leading causes of cancer mortality in women. Despite the advancement in endocrine therapy and the addition of cyclin dependent kinase (CDK) 4/6 inhibitors, patients eventually become refractory to treatment creating a desperate need for the development of alternative therapies. Previously, we discovered HACE1, the E3 ubiquitin ligase that targets the small GTPase Rac1 for proteasomal mediated degradation. HACE1 is commonly lost in estrogen receptor (ER) positive and HER2 positive breast cancers and results in the hyperactivation of the Rac signaling pathway. Here, we show that Rac1 resides in the estrogen receptor transcriptional complex and acts as a critical estrogen receptor transcriptional co-activator. The dependency of Rac on ER transcription is further exemplified by the treating ER+ breast cancer cells with a Rac inhibitor where transcriptional profiling identified ER target genes were preferentially down-regulated. Thus, we confirm the dependency of Rac1 in ER+ breast cancers and show that Rac1 is necessary for estrogen receptor transcriptional activity. Importantly, we show that a novel Rac1 inhibitor is capable of reducing estrogen receptor transcriptional activity as well as impairing cellular proliferation and migration. Moreover, Rac inhibition is shown to enhance the anti-tumor effects of fulvestrant both in vitro and in vivo, including in a patient-derived-xenograft (PDX) model of ER+ disease. Lastly, we demonstrate that the administration of a novel Rac inhibitor is well-tolerated after chronic dosing in both small and large animal species. Together these data suggest a new potential pathway for treating hormone dependent breast cancer. Citation Format: Erik T Goka, Jun Sun, Dayrelis T Mesa Lopez, Marc E Lippman. Rac inhibition as an alternative approach to treating hormone dependent breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-10-13.
A Randomized, Controlled Trial of Liraglutide for Adolescents with Obesity
Authors: Aaron S. Kelly, Pernille Auerbach, Margarita Barrientos-Perez, Inge Gies, Paula M. Hale, Claude Marcus, Lucy D. Mastrandrea, Nandana Prabhu, Silva Arslanian
Journal: New England Journal of Medicine (2020)

Obesity is a chronic disease with limited treatment options in pediatric patients. Liraglutide may be useful for weight management in adolescents with obesity.In this randomized, double-blind trial, which consisted of a 56-week treatment period and a 26-week follow-up period, we enrolled adolescents (12 to <18 years of age) with obesity and a poor response to lifestyle therapy alone. Participants were randomly assigned (1:1) to receive either liraglutide (3.0 mg) or placebo subcutaneously once daily, in addition to lifestyle therapy. The primary end point was the change from baseline in the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) standard-deviation score at week 56.A total of 125 participants were assigned to the liraglutide group and 126 to the placebo group. Liraglutide was superior to placebo with regard to the change from baseline in the BMI standard-deviation score at week 56 (estimated difference, -0.22; 95% confidence interval [CI], -0.37 to -0.08; P = 0.002). A reduction in BMI of at least 5% was observed in 51 of 113 participants in the liraglutide group and in 20 of 105 participants in the placebo group (estimated percentage, 43.3% vs. 18.7%), and a reduction in BMI of at least 10% was observed in 33 and 9, respectively (estimated percentage, 26.1% vs. 8.1%). A greater reduction was observed with liraglutide than with placebo for BMI (estimated difference, -4.64 percentage points) and for body weight (estimated difference, -4.50 kg [for absolute change] and -5.01 percentage points [for relative change]). After discontinuation, a greater increase in the BMI standard-deviation score was observed with liraglutide than with placebo (estimated difference, 0.15; 95% CI, 0.07 to 0.23). More participants in the liraglutide group than in the placebo group had gastrointestinal adverse events (81 of 125 [64.8%] vs. 46 of 126 [36.5%]) and adverse events that led to discontinuation of the trial treatment (13 [10.4%] vs. 0). Few participants in either group had serious adverse events (3 [2.4%] vs. 5 [4.0%]). One suicide, which occurred in the liraglutide group, was assessed by the investigator as unlikely to be related to the trial treatment.In adolescents with obesity, the use of liraglutide (3.0 mg) plus lifestyle therapy led to a significantly greater reduction in the BMI standard-deviation score than placebo plus lifestyle therapy. (Funded by Novo Nordisk; NN8022-4180 ClinicalTrials.gov number, NCT02918279.).
Impact of Shared Care in Remote Areas for Patients With Left Ventricular Assist Devices
Authors: Michael Yaoyao Yin, Jennifer Strege, Edward M. Gilbert, Josef Stehlik, Stephen H. McKellar, Ashley Elmer, Thomas Anderson, Mossab Aljuaid, Jose Nativi-Nicolau, Antigone G. Koliopoulou, Erin Davis, James C. Fang, Stavros G. Drakos, Craig H. Selzman, Omar Wever-Pinzon
Journal: JACC Heart Failure (2020)
Pancreatic Adenocarcinoma: Unconventional Approaches for an Unconventional Disease
Authors: Christopher Gromisch, Motaz Qadan, Mariana Albuquerque Machado, Kebin Liu, Yolonda Colson, Mark W. Grinstaff
Journal: Cancer Research (2020)

Abstract This review highlights current treatments, limitations, and pitfalls in the management of pancreatic cancer and discusses current research in novel targets and drug development to overcome these clinical challenges. We begin with a review of the clinical landscape of pancreatic cancer, including genetic and environmental risk factors, as well as limitations in disease diagnosis and prevention. We next discuss current treatment paradigms for pancreatic cancer and the shortcomings of targeted therapy in this disease. Targeting major driver mutations in pancreatic cancer, such as dysregulation in the KRAS and TGFβ signaling pathways, have failed to improve survival outcomes compared with nontargeted chemotherapy; thus, we describe new advances in therapy such as Ras-binding pocket inhibitors. We then review next-generation approaches in nanomedicine and drug delivery, focusing on preclinical advancements in novel optical probes, antibodies, small-molecule agents, and nucleic acids to improve surgical outcomes in resectable disease, augment current therapies, expand druggable targets, and minimize morbidity. We conclude by summarizing progress in current research, identifying areas for future exploration in drug development and nanotechnology, and discussing future prospects for management of this disease.
Abstract 12787: Impact of Different P2Y12 Inhibitors on Cardiovascular Outcomes in Diabetic versus Non-Diabetic Patients: Insights From Real-World Data
Authors: Mohamed H Shahin, Lukas G Kovar, D. Max Smith, Amanda R Elsey, Kristin W Weitzel, R. David Anderson, Rhonda M Cooper-DeHoff, David R Nelson, Julie A Johnson, Larisa H Cavallari
Journal: Circulation (2018)

Introduction: Impaired response to antiplatelet therapy in diabetic patients has been reported; however, limited studies have tested the effect of different P2Y12 inhibitors on cardiovascular outco...
Significant weight loss in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database
Authors: Michael Hughes, Calvin Heal, Elise Siegert, Eric Hachulla, Paolo Airó, Antonella Riccardi, Oliver Distler, Marco Matucci-Cerinic
Journal: Annals of the Rheumatic Diseases (2020)

Organ involvement is collected in the MEDS of the EULAR Scleroderma Trials and Research database. 6Lung disease/ILD was defined as forced vital capacity (FVC) <70%.P values are presented as uncorrected values for multiple testing due to the exploratory nature of the analysis.Associations of significant weight loss after application of Holm-Bonferroni correction are presented within the body of the text.ANA, anti-nuclear antibody;
The NCDR Left Atrial Appendage Occlusion Registry
Authors: James V. Freeman, Paul Varosy, Matthew J. Price, David Slotwiner, Fred M. Kusumoto, Chidambaram Rammohan, Clifford J. Kavinsky, Zoltan G. Turi, Joseph Akar, Cristina Koutras, Jeptha P. Curtis, Frederick A. Masoudi
Journal: Journal of the American College of Cardiology (2020)
Abstract 14074: Low-Level Electromagnetic Fields Attenuate the Inducibility of Atrial Fibrillation
Authors: Daniel Sohinki, Stavros Stavrakis, Sunny S Po, Julie Stoner, Benjamin J Scherlag
Journal: Circulation (2019)

Introduction: Recent research suggests that autonomic nervous system (ANS) dysfunction contributes to the initiation and maintenance of AF, and several studies have demonstrated the effectiveness o...
Abstract P5-11-03: Practice patterns and outcomes of post progression treatment after CDK 4/6 inhibitors
Authors: Katherine Keaney Clifton, Akshara Singareeka Raghavendra, Min Yi, Jennifer Litton, Debu Tripathy, Meghan Karuturi
Journal: Cancer Research (2020)

Abstract Background: CDK 4/6 inhibitors have become frontline treatment for patients (pts) with advanced hormone receptor (HR) positive breast cancer. There is limited data regarding post-progression outcomes in pts receiving CDK 4/6 inhibitors as standard of care. In this study, we analyzed treatment patterns and clinical outcomes of post-progression treatment in pts with advanced HR positive breast cancer after receiving CDK 4/6 inhibitors. Methods: Pts with metastatic breast cancer receiving CDK 4/6 inhibitors who received treatment after progression were identified from a cohort of pts at MDACC. Pts receiving CDK 4/6 inhibitors in a clinical trial were excluded. Clinical and demographic data as well as progression-free survival (PFS) was collected. Data was analyzed using Fischer's exact test for categorized variables and T test/Wilcoxon rank-sum test for continuous variables. PFS was analyzed using the Kaplan Meier method. Results: 206 pts who met eligibility criteria were included. Median age at metastatic diagnosis was 56 years-old and the majority of pts were white (n=160, 77.7%) with a pre- treatment performance status of 0 (n=168, 81.6%). The largest fraction of pts (n=98, 47.6%) received a chemotherapy agent following progression on a CDK 4/6 inhibitor while 19.4% (n=40) received endocrine therapy, 21.8% (n=45) received a biologic, 6.3% (N=13) received a different CDK 4/6 inhibitor and 4.9% (n=10) received an investigational therapy. The majority of pts who progressed on a subsequent agent had visceral progression (n=193, 93.7%). The median time to progression on an agent after CDK 4/6 inhibitor was 122 days. There was no statically significant difference in time to progression after CDK 4/6 inhibitor between pts receiving different classes of therapies, including CDK 4/6 inhibitors and investigational therapies (p=0.3). Conclusion: Pts in our cohort were more likely to receive chemotherapy following progression on a CDK 4/6 inhibitor. Reassuringly, there was no significant difference between time to progression on different agents. As CDK 4/6 inhibitors become frontline therapy for HR positive metastatic breast cancer, it is important to evaluate the sequencing of therapies as well as outcomes on subsequent agents. Citation Format: Katherine Keaney Clifton, Akshara Singareeka Raghavendra, Min Yi, Jennifer Litton, Debu Tripathy, Meghan Karuturi. Practice patterns and outcomes of post progression treatment after CDK 4/6 inhibitors [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-11-03.