tbuckley/cabot-search huggingface dataset:
Review of Current Advances in the Mechanical Description and Quantification of Aortic Dissection Mechanisms
Authors: Joseph Brunet, Baptiste Pierrat, Pierre Badel
Journal: IEEE Reviews in Biomedical Engineering (2020)

Aortic dissection is a life-threatening event associated with a very poor outcome. A number of complex phenomena are involved in the initiation and propagation of the disease. Advances in the comprehension of the mechanisms leading to dissection have been made these last decades, thanks to improvements in imaging and experimental techniques. However, the micro-mechanics involved in triggering such rupture events remains poorly described and understood. It constitutes the primary focus of the present review. Towards the goal of detailing the dissection phenomenon, different experimental and modeling methods were used to investigate aortic dissection, and to understand the underlying phenomena involved. In the last ten years, research has tended to focus on the influence of microstructure on initiation and propagation of the dissection, leading to a number of multiscale models being developed. This review brings together all these materials in an attempt to identify main advances and remaining questions.
Prophylactic cranial irradiation in patients ≥ 70 years old with limited stage small cell lung cancer: A Surveillance, Epidemiology, and End Results analysis.
Authors: Bree Ruppert Eaton, David Mitchell Marcus, Sungjin Kim, Zhengjia Chen, Suresh S Ramalingam, Walter J. Curran, Kristin Higgins
Journal: Journal of Clinical Oncology (2013)

7589 Background: Prophylactic cranial irradiation (PCI) improves survival in patients with limited stage small cell lung cancer (SCLC) who have a complete response to chemotherapy and radiation (RT). Yet in clinical practice, concerns exist regarding PCI-related toxicity and the extent of benefit in elderly patients. This exploratory analysis evaluates the effect of PCI on survival among patients ≥ 70 years old. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified 4,003 patients ≥70 years old with localized or regional SCLC diagnosed between 1988 and 1997. Patients with no brain RT information (n=974) were excluded. Patients with overall survival (OS) &lt;6 months (n=1103) were also excluded to eliminate patients with an aggressive disease course and minimize selection bias. Survival rates for patients who received brain RT versus no brain RT were estimated by the Kaplan Meier method and compared with the Log-rank test. A Cox proportional hazards model was further fitted to estimate the effect of brain RT on OS after adjusting for age, race, gender, and stage. Results: Of the 1926 patients included, the median age was 75 years (range, 70-94). The majority of patients were white (68%) and male (52%). According to SEER Historic Stage A, 68% of patients had regional stage and 32% had localized stage. One-hundred and thirty-eight patients (7.2%) received brain RT. Patients treated with brain RT were younger at diagnosis (p&lt;0.01) and more likely to have regional stage disease (p=0.02). Five-year OS was 11.6% (95% CI: 6.9-17.6) among patients who received brain RT versus 8.6% (95% CI: 7.32-9.91) among patients who did not (p=0.03). Younger age, female gender, white race, and localized stage were also significant factors associated with improved OS. On multi-variable analysis, receipt of brain RT remained an independent predictor of OS (HR 0.825, 95% CI: 0.69-0.98, p=0.03). Conclusions: The receipt of brain radiotherapy is associated with improved overall survival in patients ≥70 years old with localized or regional stage SCLC, suggesting the benefit of PCI is maintained in the elderly population.
Correspondence on 'Immune checkpoint inhibitor-induced inflammatory arthritis persists after immunotherapy cessation’ by Braaten <i>et al</i>
Authors: Fulvia Ceccarelli, Andrea Botticelli, Alain Jonathan Gelibter, Ilaria Leccese, Ramona Lucchetti, Enrico Cortesi, Guido Valesini, Paolo Marchetti, Fabrizio Conti
Journal: Annals of the Rheumatic Diseases (2020)

Immune checkpoint inhibitor-induced inflammatory arthritis persists after immunotherapy cessation' by Braaten et al: another point of viewWe read with interest the study published by Braaten and colleagues, analysing the long-term outcomes of 60 patients developing persistent inflammatory arthritis (IA) after immune checkpoint inhibitors (ICIs) cessation.The most relevant result of the study was the presence of active arthritis in more than half of the patients at the last follow-up visit. 1 We report here our experience in the context of a joint oncology/rheumatology outpatient clinic, in order to evaluate the risk of developing IA in patients treated by anti-PD1 drugs.During 1-year period, we consecutively assessed all the adult patients candidate to anti-PD1 treatment, referring to the Oncology Unit at the Sapienza University of Rome.After treatment starts, in the case of musculoskeletal manifestations, patients were referred to the Sapienza Arthritis Center, Rheumatology Unit, Sapienza University of Rome.Arthritis was defined as the occurrence of at least one episode of clinical synovitis, with morning stiffness lasting at least 30 min.IA activity was assessed by disease activity score on 28 joints by ESR (DAS28-ESR). 2We investigated the presence of rheumatoid factor (RF), anticitrullinated protein (ACPA) and antinuclear antibodies.In the clinically involved joints, ultrasonographic assessment was performed according to EULAR guidelines. 3e evaluated 72 patients (M/F 48/24, median age 66 years, IQR 13.0) affected by lung cancer (75.1%), renal cancer (15.3%), melanoma skin cancer (6.9%), or other neoplastic diseases (2.7%).Sixty-seven patients were treated with nivolumab and the remaining with pembrolizumab (median treatment duration 7 months, IQR 13.0).After 3 months of follow-up, the malignant disease had not progressed in 48 patients (66.7%), whereas an exitus was registered in 21 patients (29.2%).During the follow-up period, seven Caucasian patients (9.7%) developed clinically evident synovitis (absolute risk for IA 0.1, incidence rate 0.01).Table 1 reports the main demographic, oncologic
Novel Germline Mutations in DNA Damage Repair in Patients with Malignant Pleural Mesotheliomas
Authors: Robin Guo, Mariel DuBoff, Gowtham Jayakumaran, Mark G. Kris, Marc Ladanyi, Mark E. Robson, Diana Mandelker, Marjorie G. Zauderer
Journal: Journal of Thoracic Oncology (2019)
From a "Eureka Insight" to a Novel Potential Therapeutic Target to Treat Alzheimer's Disease
Authors: Bergantin Leandro Bueno
Journal: Alzheimers Disease & Dementia (2017)

It has been almost 4 years since we revealed the solution for the enigma of the so-called 'calcium paradox'. Our discovery of the involvement of Ca2+/cAMP signaling interaction in the regulation of neurotransmitter release, and neuro protection, was clearly a serendipitous discovery. It has produced new avenues in the understanding of the cellular and molecular mechanisms involved in the pathogenesis of neurological and psychiatric disorders, such as Alzheimer's disease. Interestingly, this discovery initiated decades ago when numerous clinical studies have reported that use of L-type Ca2+ channel blockers (CCBs) by hypertensive patients decreased arterial pressure, but produced typical symptoms of sympathetic hyperactivity, such as tachycardia and increment of catecholamine plasma levels.
The Effect of Cardiogenic Factors on Cardiac Mesenchymal Cell Anti-Fibrogenic Paracrine Signaling and Therapeutic Performance
Authors: Justin S. Heidel, Annalara G. Fischer, Xian-Liang Tang, Ghazal Sadri, Wen-Jian Wu, Claudiu R. Moisa, Heather Stowers, Neel Sandella, Marcin Wysoczynski, Shizuka Uchida, Joseph B. Moore IV
Journal: Theranostics (2020)

Intrinsic cardiogenic factor expression, a proxy for cardiomyogenic lineage commitment, may be an important determinant of donor cell cardiac reparative capacity in cell therapy applications; however, whether and how this contributes to their salutary effects remain largely ambiguous. Methods: The current study examined the consequences of enhanced cardiogenic factor expression, via lentiviral delivery of GMT (GATA4, MEF2C, and TBX5), on cardiac mesenchymal cell (CMC) anti-fibrogenic paracrine signaling dynamics, in vitro, and cardiac reparative capacity, in vivo. Proteome cytokine array analyses and in vitro cardiac fibroblast activation assays were performed using conditioned medium derived from either GMT- or GFP control-transduced CMCs, to respectively assess cardiotrophic factor secretion and anti-fibrogenic paracrine signaling aptitude. Results: Relative to GFP controls, GMT CMCs exhibited enhanced secretion of cytokines implicated to function in pathways associated with matrix remodeling and collagen catabolism, and more ably impeded activated cardiac fibroblast Col1A1 synthesis in vitro. Following their delivery in a rat model of chronic ischemic cardiomyopathy, conventional echocardiography was unable to detect a therapeutic advantage with either CMC population; however, hemodynamic analyses identified a modest, yet calculable supplemental benefit in surrogate measures of global left ventricular contractility with GMT CMCs relative to GFP controls. This phenomenon was neither associated with a decrease in infarct size nor an increase in viable myocardium, but with only a marginal decrease in regional myocardial collagen deposition. Conclusion: Overall, these results suggest that CMC cardiomyogenic lineage commitment biases cardiac repair and, further, that enhanced anti-fibrogenic paracrine signaling potency may underlie, in part, their improved therapeutic utility.
Clinicopathological Characteristics and Breast Cancer–Specific Survival of Patients With Single Hormone Receptor–Positive Breast Cancer
Authors: Yunhai Li, Dejuan Yang, Xuedong Yin, Xiang Zhang, Jiefeng Huang, Yusheng Wu, Mengxue Wang, Zhiying Yi, Hongyuan Li, Hongzhong Li, Guosheng Ren
Journal: JAMA Network Open (2020)

Steroid hormone receptors, including estrogen receptor (ER) and progesterone receptor (PR), are crucial biomarkers in breast cancer (BC). However, limited data are available regarding single hormone receptor-positive (ER-positive/PR-negative and ER-negative/PR-positive) subtypes, rendering treatment decision and survival forecast difficult in patients with these BC subtypes.To investigate the clinicopathological characteristics and BC-specific survival (BCSS) of patients with single hormone receptor-positive BC.In this cohort study, data on patients diagnosed with BC between 1990 and 2015 were retrieved from the Surveillance, Epidemiology, and End Results database (N = 1 158 032). Patients lacking information on ER status, PR status, or BCSS were excluded (n = 334 633). Comparisons were performed between single hormone receptor-positive BC and double hormone receptor-positive/double hormone receptor-negative BC. The dates of analysis were September 1, 2018, to June 31, 2019.The BCSS of patients with single hormone receptor-positive BC.This cohort study included 823 399 patients with BC (818 002 women and 5397 men). The median (range) age at diagnosis was 60 (8-108) years, and the median (range) follow-up duration was 71 (0-311) months. The percentages of ER-positive/PR-positive, ER-positive/PR-negative, ER-negative/PR-positive, and ER-negative/PR-negative cases were 67.2%, 12.2%, 1.6%, and 19.0%, respectively. Single hormone receptor-positive subtypes showed distinct clinical characteristics compared with double hormone receptor-positive/double hormone receptor-negative subtypes. Multivariable Cox proportional hazards regression analysis showed that patients with ER-positive/PR-negative (hazard ratio [HR], 1.36; 95% CI, 1.34-1.38) and ER-negative/PR-positive (HR, 1.61; 95% CI, 1.55-1.67) tumors had worse BCSS than patients with the ER-positive/PR-positive subtype. In contrast, patients with ER-positive/PR-negative (HR, 1.27; 95% CI, 1.24-1.29) and ER-negative/PR-positive (HR, 1.07; 95% CI, 1.03-1.11) tumors had better BCSS than patients with the ER-negative/PR-negative subtype. The BCSS was statistically significantly worse in patients with ER-negative/PR-positive tumors than in patients with ER-positive/PR-negative tumors (HR, 1.18; 95% CI, 1.14-1.23).In this cohort study, statistically significant distinctions between survival rates of patients with single hormone receptor-positive BC vs double hormone receptor-positive/double hormone receptor-negative BC were observed. Different strategies may be required for patients with single hormone receptor-positive tumors to ensure optimal treatment and maximum benefits from therapies.
NCMP-16. IMMUNO-ONCOTHERAPY (IO) PROVOKED ENCEPHALITIS AND METASTATIC MIMICRY: PATIENT WITH HISTORY OF RENAL CELL CARCINOMA ON IO PRESENTS WITH SEIZURE, FIELD CUT, AND BRAIN MASS
Authors: Na Tosha Gatson, Mayur Patel, Michelle Grant, Julie Woods, Gino Mongelluzzo, Andrew Conger
Journal: Neuro-Oncology (2019)

Abstract With the success of immuno-oncotherapy (IO) to treat systemic cancers came the risk for multi-organ autoimmune inflammation (esophagitis, colitis, hypophysitis, pneumonitis, etc.). Immune-mediated encephalitis, however, has been only rarely described in patients treated on IO. Here we present the first case of a 70-year-old male with history of clear cell renal cell carcinoma (CCRCC, Fuhrman grade 4, April 2017) post-nephrectomy with early progressive pulmonary metastases treated with pazopanib before switching to single-agent nivolumab (February 2018) with demonstrated early response. Further progression (March 2019) added body irradiation and continued systemic nivolumab with questionable medication-induced dermatitis. Patient presented to ED in May 2019 with new-onset generalized tonic-clonic seizure, left visual field cut, and 4.6cm heterogeneous enhancing right occipital mass with vasogenic edema on brain MRI, presumed metastasis. However, unknown to the patient was a remote area of right occipital encephalomalacia (found on skull-based portion of staging PET, July 2018) presumed silent stroke or TBI endorsed 20-years-ago. Patient started anti-epileptic therapy and underwent negative CSF evaluation before neurosurgical resection. Tissue pathology concerning for lymphoproliferative malignancy versus reactive lymphocytic infiltrate with perivascular distribution of monomorphic CD4+ T-cell predominance (97%) and positive T-cell receptor (gamma, beta) gene rearrangement. While clonal T-cell populations are highly suggestive of T-cell malignancies, reactive conditions can also rarely show clonal T-cell populations. Patient underwent a negative systemic staging for lymphoma and IO was discontinued without immediate initiation of steroids. Follow up clinical evaluation reveal patient improved off IO therapy. Patient was determined to have reactive immune-mediated encephalitis secondary to IO therapy causing seizure mimicking brain metastasis of primary CCRCC. Interestingly, the prior area of encephalomalacia allowed for a cellular bed to collect, resembling brain mass. Upfront staging brain MRI prior to starting IO might have revealed susceptible area and could be considered in these patients
Post-treatment survival difference between lobectomy and stereotactic ablative radiotherapy in stage I non-small cell lung cancer in England
Authors: Aamir Khakwani, Susan Harden, Paul Beckett, David Baldwin, Neal Navani, Doug West, Richard Hubbard
Journal: Thorax (2019)

Approximately 15%-20% of all non-small cell lung cancer (NSCLC) cases present with stage I disease. Surgical resection traditionally offers the best chance of a cure but some patients will not have this treatment due to older age, comorbidities or personal choice. Stereotactic ablative radiotherapy (SABR) has become an established curative intent treatment option for patients who are not selected for or do not choose surgery. The aim of this study is to compare survival at 90 days, 6 months, 1 year and 2 years for patients who received either lobectomy or SABR.We used data from the 2015 National Lung Cancer Audit database and linked with Hospital Episode Statistics and the radiotherapy dataset to identify patients with NSCLC stage IA-IB and performance status (PS) 0-2 who underwent surgery or SABR treatment. We assessed the likelihood of death at 90 days, 6 months, 1 year and 2 year after diagnosis and procedure date to observe survival between two patient groups.We identified 2373 patients in our cohort, 476 of whom had SABR. The median difference between date of diagnosis and date of treatment for surgery patients was 17 days while for SABR patients it was 73 days. Increasing age and worsening PS were associated with having SABR rather than surgery. Survival between the two treatment modalities was similar early on but by 1-year people who had surgery did better than those who had SABR (adjusted ORs 2.12, 95% CI 1.35 to 2.31). This difference persisted at 2 years and when the analysis was restricted to patients aged <80 years and with PS 0 or 1 and stage IA only.Our analysis suggests that patients who have lobectomy have a better survival compared with SABR patients; however, we found considerable delays in patients receiving SABR which may contribute to poorer long-term outcomes with this treatment option. Reducing these delays should be a key focus in development and reorganisation of services.
Integrated drug profiling and CRISPR screening identify essential pathways for CAR T-cell cytotoxicity
Authors: Olli Dufva, Jan Koski, Pilvi Maliniemi, Aleksandr Ianevski, Jay Klievink, Judith Leitner, Petri Pölönen, Helena Hohtari, Khalid Saeed, Tiina Hannunen, Pekka Ellonen, Peter Steinberger, Matti Kankainen, Tero Aittokallio, Mikko A. I. Keränen, Matti Korhonen, Satu Mustjoki
Journal: Blood (2019)
Abstract 13652: The Anti-Hypertensive Effects of LCZ696 in Patients With Hypertension: A Meta-Analysis of Randomized Controlled Trials
Authors: Su-Kiat Chua, Chiung-Zuan Chiu
Journal: Circulation (2019)

Introduction: Sacubitril/vasartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor approved for the treatment of heart failure with reduced ejection fraction. To determine the...
What face familiarity feelings say about the lateralization of specific entities within the core system
Authors: Guido Gainotti
Journal: Behavioral and Brain Sciences (2019)

Abstract The target article carefully describes the memory system, centered on the temporal lobe that builds specific memory traces. It does not, however, mention the laterality effects that exist within this system. This commentary briefly surveys evidence showing that clear asymmetries exist within the temporal lobe structures subserving the core system and that the right temporal structures mainly underpin face familiarity feelings.
Abstract 12267: Efficacy and Safety of Alirocumab in Statin-Intolerant Patients Over 3 Years: Open-Label Extension of the ODYSSEY ALTERNATIVE Trial
Authors: Patrick M Moriarty, Paul D Thompson, Christopher P Cannon, John R Guyton, Jean Bergeron, Franklin J Zieve, Eric Bruckert, Terry A Jacobson, Marie T Baccara-Dinet, Jian Zhao, Stephen Donahue, Shazia Ali, Robert Pordy, Daniel A Gipe
Journal: Circulation (2018)

Background: The 24-week randomized, double-blind (DB) ODYSSEY ALTERNATIVE (NCT01709513) trial demonstrated significant LDL-C reductions with the PCSK9 inhibitor alirocumab versus ezetimibe in stati...
Can animal models really teach us anything about pneumonia? Pro
Authors: Carlos J. Orihuela, Ulrich A. Maus, Jeremy S. Brown
Journal: European Respiratory Journal (2020)

<b>Animal models can provide incredibly detailed data on pathogenesis and immunology of lung infections, and will be essential for the development of novel therapeutic/preventative strategies to reduce the morbidity and mortality caused by pneumonia</b>http://bit.ly/2pdCzcH
Gold nanoclusters elicit homeostatic perturbations in glioblastoma cells and adaptive changes of lysosomes
Authors: Dusica Maysinger, Evan R. Gran, Franck Bertorelle, Hussein Fakhouri, Rodolphe Antoine, Esha S. Kaul, Dana M. Samhadaneh, Ursula Stochaj
Journal: Theranostics (2020)

Unique physicochemical features place gold nanoclusters at the forefront of nanotechnology for biological and biomedical applications. To date, information on the interactions of gold nanoclusters with biological macromolecules is limited and restricts their use in living cells. Methods: Our multidisciplinary study begins to fill the current knowledge gap by focusing on lysosomes and associated biological pathways in U251N human glioblastoma cells. We concentrated on lysosomes, because they are the intracellular destination for many nanoparticles, regulate cellular homeostasis and control cell survival. Results: Quantitative data presented here show that gold nanoclusters (with 15 and 25 gold atoms), surface-modified with glutathione or PEG, did not diminish cell viability at concentrations ≤1 µM. However, even at sublethal concentrations, gold nanoclusters modulated the abundance, positioning, pH and enzymatic activities of lysosomes. Gold nanoclusters also affected other aspects of cellular homeostasis. Specifically, they stimulated the transient nuclear accumulation of TFEB and Nrf2, transcription factors that promote lysosome biogenesis and stress responses. Moreover, gold nanoclusters also altered the formation of protein aggregates in the cytoplasm. The cellular responses elicited by gold nanoclusters were largely reversible within a 24-hour period. Conclusions: Taken together, this study explores the subcellular and molecular effects induced by gold nanoclusters and shows their effectiveness to regulate lysosome biology. Our results indicate that gold nanoclusters cause homeostatic perturbations without marked cell loss. Notably, cells adapt to the challenge inflicted by gold nanoclusters. These new insights provide a framework for the further development of gold nanocluster-based applications in biological sciences.
Abstract 16690: Acute Inhibition of HDACs After MI Leads to Suppression of Angiogenesis through Reduced IL-6 Signaling
Authors: Sudhakar Veeranki, Suresh C Tyagi
Journal: Circulation (2017)

Introduction: Although histone deacetylase inhibitors (HDACi) confer protection after myocardial injury (MI), the changes in the profiles of the angiogenic regulators are unknown after the usage of...