tbuckley/cabot-search huggingface dataset:
Image-guided thermosensitive liposomes for focused ultrasound drug delivery: Using NIRF-labelled lipids and topotecan to visualise the effects of hyperthermia in tumours
Authors: Miguel N. Centelles, Michael Wright, Po-Wah So, Maral Amrahli, Xiao Yun Xu, Justin Stebbing, Andrew D. Miller, Wladyslaw Gedroyc, Maya Thanou
Journal: Journal of Controlled Release (2018)
Accumulation of follicular CD8+ T cells in pathogenic SIV infection
Authors: Sara Ferrando-Martinez, Eirini Moysi, Amarendra Pegu, Sarah Andrews, Krystelle Nganou Makamdop, David Ambrozak, Adrian B. McDermott, David Palesch, Mirko Paiardini, George N. Pavlakis, Jason M. Brenchley, Daniel Douek, John R. Mascola, Constantinos Petrovas, Richard A. Koup
Journal: Journal of Clinical Investigation (2018)

LN follicles constitute major reservoir sites for HIV/SIV persistence. Cure strategies could benefit from the characterization of CD8+ T cells able to access and eliminate HIV-infected cells from these areas. In this study, we provide a comprehensive analysis of the phenotype, frequency, localization, and functionality of follicular CD8+ T cells (fCD8+) in SIV-infected nonhuman primates. Although disorganization of follicles was a major factor, significant accumulation of fCD8+ cells during chronic SIV infection was also observed in intact follicles, but only in pathogenic SIV infection. In line with this, tissue inflammatory mediators were strongly associated with the accumulation of fCD8+ cells, pointing to tissue inflammation as a major factor in this process. These fCD8+ cells have cytolytic potential and can be redirected to target and kill HIV-infected cells using bispecific antibodies. Altogether, our data support the use of SIV infection to better understand the dynamics of fCD8+ cells and to develop bispecific antibodies as a strategy for virus eradication.
Therapeutic plasma-exchange improves systemic inflammation and survival in patients with acute on chronic liver failure
Authors: R. Maiwall, A. Choudhury, Z. Duan, Y. Chen, J. Hu, H.L. Ghazinyan, Q. Ning, K. Ma, G.H. Lee, S.G. Lim, S. Shah, C. Kalal, A.K. Dokmeci, G. Kumar, P. Jain, I. Paulson, S.K. Sarin, A. Choudhury
Journal: Journal of Hepatology (2018)
Comparison of resistance profiles among DAA-naive and DAA-experienced patients infected with HCV non-1 genotype in Italy
Authors: V.C.D. Maio, S. Barbaliscia, E. Teti, I. Lenci, M. Aragri, E. Polilli, G. Fiorentino, V.P. Palitti, B. Bruzzone, S. Paolucci, C. Nicola, T. Ruggiero, T. Pollicino, F. Niero, V. Micheli, L.A. Nicolini, S. Marenco, A. Bertoli, I.R. Maida, S. Francioso, L. Foroghi, V. Calvaruso, F. Morisco, A. Lleo, V. Boccaccio, A. Ciancio, R. Maserati, M. Puoti, M. Zazzi, B. Rossetti, V. Vullo, R. D'ambrosio, L. Boglione, S. Bonora, S. Babudieri, G.A. Gubertini, M.G. Rendina, A. Pellicelli, V. Sangiovanni, A. Ciaccio, G. Taliani, G. Raimondo, G.B. Gaeta, A. Craxi, C. Pasquazzi, L. Sarmati, G. Parruti, M. Angelico, M. Andreoni, V. Cento, C.F. Perno, F.C. Silberstein
Journal: Journal of Hepatology (2018)
The Drug Overdose Epidemic and Deceased-Donor Transplantation in the United States
Authors: Christine M. Durand, Mary G. Bowring, Alvin G. Thomas, Lauren M. Kucirka, Allan B. Massie, Andrew Cameron, Niraj M. Desai, Mark Sulkowski, Dorry L. Segev
Journal: Annals of Internal Medicine (2018)

The epidemic of drug overdose deaths in the United States has led to an increase in organ donors.To characterize donors who died of overdose and to analyze outcomes among transplant recipients.Prospective observational cohort study.Scientific Registry of Transplant Recipients, 1 January 2000 to 1 September 2017.138 565 deceased donors; 337 934 transplant recipients at 297 transplant centers.The primary exposure was donor mechanism of death (overdose-death donor [ODD], trauma-death donor [TDD], or medical-death donor [MDD]). Patient and graft survival and organ discard (organ recovered but not transplanted) were compared using propensity score-weighted standardized risk differences (sRDs).A total of 7313 ODDs and 19 897 ODD transplants (10 347 kidneys, 5707 livers, 2471 hearts, and 1372 lungs) were identified. Overdose-death donors accounted for 1.1% of donors in 2000 and 13.4% in 2017. They were more likely to be white (85.1%), aged 21 to 40 years (66.3%), infected with hepatitis C virus (HCV) (18.3%), and increased-infectious risk donors (IRDs) (56.4%). Standardized 5-year patient survival was similar for ODD organ recipients compared with TDD organ recipients (sRDs ranged from 3.1% lower to 3.9% higher survival) and MDD organ recipients (sRDs ranged from 2.1% to 5.2% higher survival). Standardized 5-year graft survival was similar between ODD and TDD grafts (minimal difference for kidneys and lungs, marginally lower [sRD, -3.2%] for livers, and marginally higher [sRD, 1.9%] for hearts). Kidney discard was higher for ODDs than TDDs (sRD, 5.2%) or MDDs (sRD, 1.5%); standardization for HCV and IRD status attenuated this difference.Inability to distinguish between opioid and nonopioid overdoses.In the United States, transplantation with ODD organs has increased dramatically, with noninferior outcomes in transplant recipients. Concerns about IRD behaviors and hepatitis C among donors lead to excess discard that should be minimized given the current organ shortage.National Institutes of Health.
David Oliver: Falls in older people—can we really make a difference?
Authors: David Oliver
Journal: BMJ (2018)

This month an Observer headline reported a 177% increase in deaths from falls among men over 85 from 2008 to 2016, although the population of over 85s rose only 19%. It linked the story to serious cuts in social care funding and provision in that period: a fall from 15% to 9% of over 65s receiving council funded care.1 It’s hard to establish a causal link, but the story highlights the importance of falls to our health and care services.

Around a third of over 65s and half of over 80s fall at least once a year, and half fall again in the same year.2 Falls are the leading cause of death from …
High miR-224 expression in cholangiocarcinoma may predict survival
Authors: T. Szekerczés, I. Coati, M. Fassan, K. Schlachter, G. Lendvai, E. Szabó, M. Csengeri, Á. Rácz, K. Borka, Z. Schaff, A. Kiss
Journal: Journal of Hepatology (2018)
Effect of PET-CT on disease recurrence and its management in patients with potentially resectable colorectal cancer liver metastases: The long-term results of a randomized control trial.
Authors: Pablo Emilio Serrano Aybar, Chu-Shu Gu, Mohamed Husien, Diederick Jalink, Guillaume Martel, Melanie E. Tsang, Julie I. Hallet, Steven Gallinger, Anne Ritter, Vivian McAlister, Nathalie Sela, Hannah Solomon, Kaitlyn Beyfuss, Christine Li, Erika Lee, Carolanne Moulton, Mark Norman Levine
Journal: Journal of Clinical Oncology (2018)

562 Background: The PETCAM randomized trial evaluated the effect of preoperative PET-CT (vs. no PET-CT) on surgical management in patients with colorectal cancer liver metastases. In this study, 8% of patients had a change in surgical management, including a higher proportion of major liver resections in the PET-CT arm. The current study compares the intervention groups for 5-year disease free (DFS) and overall survival (OS), and evaluated their long-term clinical course, i.e. sites of recurrence and management of disease recurrence. Methods: Recruitment to the trial occurred between 2005-2010, with last follow-up in 2013. Data on recurrence, management of recurrence and mortality from 2013-2017 was collected from patient’s charts. Recurrences according to site and management were described. Cox proportional Hazard Models were used to calculate the risk for recurrence and death. OS was calculated with Kaplan-Meir method and compared with log-rank test. Results: At 5 years, 157 of 404 (39%) patients were still alive and 19 patients were lost to follow-up. Median follow-up is 4.2 years. There were no differences in DFS (HR: 1.12, 95%CI: 0.88-1.42) or OS (HR: 0.97, 95%CI: 0.74-1.28) between groups. The median DFS for the 372 patients who had surgery was 17 months, 95%CI: 14.7-19.4. Risks factors for recurrence were: extrahepatic disease, liver tumour size, and nodal stage. The median OS for all patients was 50 months, 95%CI: 43.5-64.3. Risks factors for death also included age and prior use of chemotherapy. During the follow-up period, 287/404, 71% patients recurred (mostly liver and lung); 137 (48%) were treated solely with chemotherapy and 35% were treated with surgery with curative intent. Of these, the majority recurred (109/116, 94%). The median OS following first recurrence was 27.5 months, 95%CI: 23-30. Conclusions: PET-CT did not improve DFS or OS. Survival following liver resection is similar to previous reports, however most patients experience disease recurrence. A substantial proportion of patients who recur undergo surgery, however it is likely that they will recur again.
Microsatellite instability and adjuvant chemotherapy in stage II colon cancer.
Authors: Julie L. Koenig, Albert Y. Lin, Erqi L. Pollom, Daniel Tandel Chang
Journal: Journal of Clinical Oncology (2018)

767 Background: Randomized control trials and population-based studies have not demonstrated a definitive benefit for adjuvant chemotherapy in stage II colon cancers. Tumor side and microsatellite instability (MSI) have been proposed as prognostic and predictive factors, but there is little consensus about their utility. Previous studies have been limited by the availability of MSI data. Because microsatellite stability (MSS) is associated with worse prognosis and higher risk of metastases, we hypothesized patients with MSS would have increased benefit from chemotherapy. Methods: Using the National Cancer Database, we preformed a retrospective cohort study of patients with resected stage II colon cancer diagnosed 2006-2013. Patient and disease characteristics were compared with chi-square tests. Survival was evaluated with Cox proportional hazard models. Results: We identified 59,475 patients with stage II colon cancer. 11.4% of patients had known MSI status (n = 6,763) of which 88% had MSS (n = 5,953) and 12% had MSI (n = 810). Patients with MSS were more likely to receive chemotherapy (28.2% vs 19.9%, p &lt; 0.001) and have left-sided tumors (38.8% vs 16.7%, p &lt; 0.001). MSI (adjusted hazard ratio [HR] 0.64, 95% confidence interval [CI] 0.48-0.87; p = 0.003) and receipt of chemotherapy (HR 0.54, 95% CI 0.42-0.69; p &lt; 0.001) were associated with better survival after controlling for multiple characteristics including tumor side. Although left-sided tumors had better survival on univariate analysis (HR 0.91, 95% CI 0.88-0.94; p &lt; 0.001), side was not an independent predictor of survival after controlling for MSI and other characteristics (HR 1.01, 95% CI 0.86-1.20; p = 0.860). Among patients with MSS, chemotherapy remained associated with improved survival (HR 0.54, 95% CI 0.43-0.70; p &lt; 0.001) and this benefit did not vary by tumor side (interaction p = 0.380). There was no interaction between MSI status and chemotherapy (p = 0.139), but we observed less of a survival benefit for chemotherapy in patients with MSI (HR 0.81, 95% CI 0.38-1.75; p = 0.595). Conclusions: Our data suggest a benefit for adjuvant chemotherapy in stage II colon cancer even after adjusting for MSI status. However, tumor side was not prognostic after controlling for MSI status.
Alteration of primary cilia in COPD
Authors: Jeanne-Marie Perotin, Christelle Coraux, Eymeric Lagonotte, Philippe Birembaut, Gonzague Delepine, Myriam Polette, Gaëtan Deslée, Valérian Dormoy
Journal: European Respiratory Journal (2018)

Chronic obstructive pulmonary disease (COPD) is a major economic and social concern worldwide because of its impact on mortality and morbidity [1]. COPD is characterised by airway epithelium remodelling, a hallmark of dysregulated airway epithelium plasticity [2]. There are currently no available therapeutics to restore the integrity and functionality of the epithelium. Therefore, novel sources of investigation are becoming crucial to understand the alterations at the root of COPD initiation. Non-motile primary cilia are solitary sensor organelles playing a critical role in cell cycle control, proliferation, polarity and differentiation, particularly of ciliated cells possessing motile cilia [3, 4]. Primary cilia are assembled on different types of human cells depending on their state and activities in response to cellular quiescence where they relay extracellular signals and retract upon cell cycle re-entry [5]. Alterations of primary cilium structure and function are responsible for ciliopathies [6, 7]. Primary cilia may be crucial in determining outcomes during airway epithelial cell differentiation thus we hypothesised that primary cilia are present in adult epithelial cells and may play a key role in airway plasticity. First, we investigated the presence and localisation of primary cilia in the bronchial epithelium. Secondly, we analysed the relationships between primary cilia and clinical, functional and histological characteristics of non-COPD and COPD patients. Non-differentiated airway epithelial cells display primary cilia and their number is associated with COPD features <http://ow.ly/wiGH30jDbeG>
The Prognostic Value of Late Gadolinium-Enhanced Cardiac Magnetic Resonance Imaging in Nonischemic Dilated Cardiomyopathy
Authors: Marthe A.J. Becker, Jan H. Cornel, Peter M. van de Ven, Albert C. van Rossum, Cornelis P. Allaart, Tjeerd Germans
Journal: JACC. Cardiovascular imaging (2018)
Long‐term Outcomes in Patients With Multiple Myeloma
Authors: Silvia G.R. Verelst, Hedwig M. Blommestein, Saskia De Groot, Sebastian Gonzalez‐McQuire, Lucy DeCosta, Johan B. de Raad, Carin A. Uyl‐de Groot, Pieter Sonneveld
Journal: HemaSphere (2018)

Registry data are important for monitoring the impact of new therapies on treatment algorithms and outcomes, and for guiding clinical decision making in multiple myeloma (MM). This observational study analyzed real-world data from patients in the Population-based HAematological Registry for Observational Studies who were treated for symptomatic MM from 2008 to 2013 in the Netherlands. The primary endpoint was overall survival (OS) from initiation of first-line treatment. Secondary endpoints included OS and progression-free survival per treatment line, treatment patterns, and treatment response. Between 2008 and 2013, 917, 583, 283, and 139 patients had initiated first, second, third, and fourth treatment lines, respectively. Thalidomide-based regimens were the most frequently used first-line treatment (66%); bortezomib- and lenalidomide-based regimens were most often used in the second line (41% and 27%, respectively). The median OS (95% confidence interval) ranged from 37.5 months (34.8-41.8 months) in the first line to 9.2 months (6.2-12.3 months) in the fourth line. Univariate analyses showed that survival benefits were most apparent in younger patients (≤65 vs >65 years). These analyses provide important real-world information on treatment patterns and outcomes in patients with MM.
Oxidative modifications of extracellular matrix promote the second wave of inflammation via β2 integrins
Authors: Valentin P. Yakubenko, Kui Cui, Christopher L. Ardell, Kathleen E. Brown, Xiaoxia Z. West, Detao Gao, Samantha Stefl, Robert G. Salomon, Eugene A. Podrez, Tatiana V. Byzova
Journal: Blood (2018)
Abstract 12973: PR-Interval Components and Atrial Fibrillation Risk: The Atherosclerosis Risk In Communities Study
Authors: Wesley T O’Neal, Justin W Smith, M. B Shoemaker, Lin Y Chen, Alvaro Alonso, S. P Whalen, Elsayed Z Soliman
Journal: Circulation (2016)

Introduction: Reports on the association between the PR-interval and atrial fibrillation (AF) are conflicting. We hypothesized that inconsistencies stem from that fact that the PR-interval is not a single electrocardiographic (ECG) phenotype and it is more likely to represent a composite of several distinct components. Methods: We examined the association of the PR-interval and its components (P-wave onset to P-wave peak duration, P-wave peak to P-wave end duration, and PR-segment) with AF in 14,924 participants (mean age=54±5.8 years; 26% black; 55% female) from the Atherosclerosis Risk in Communities study. The PR-interval and its components were automatically measured at baseline (1987-1989) from standard 12-lead ECGs. PR-interval &gt;200 ms was considered prolonged and values &gt;95th percentile defined abnormal PR-interval components. AF was ascertained during follow-up through December 31, 2010. Results: Over a median follow-up of 21.2 years, 1,985 (13%) participants developed AF. Prolonged PR-interval was associated with an increased risk of AF (HR=1.19, 95% CI=1.02, 1.40). However, PR-interval components showed varying levels of associations with AF (P-wave onset to P-wave peak duration: HR=1.57, 95%CI=1.31, 1.88; P-wave peak to P-wave end duration: HR=1.20, 95%CI=0.99, 1.46; and PR-segment: HR=1.05, 95%CI=0.85, 1.29). Additionally, the components of the PR-interval had weak to moderate correlation with each other (correlation r ranged from -0.44 to 0.06). Conclusions: Our findings suggest the PR-interval represents a composite of distinct components that are not uniformly associated with AF. Without considering the contribution of each component, inconsistent associations between the PR-interval and AF are inevitable.
Epigenetic Applications in Adverse Outcome Pathways and Environmental Risk Evaluation
Authors: Michelle M. Angrish, Patrick Allard, Shaun D. McCullough, Ingrid L. Druwe, Lisa Helbling Chadwick, Erin Hines, Brian N. Chorley
Journal: Environmental Health Perspectives (2018)

Background: The epigenome may be an important interface between environmental chemical exposures and human health. However, the links between epigenetic modifications and health outcomes are often correlative and do not distinguish between cause and effect or common-cause relationships. The Adverse Outcome Pathway (AOP) framework has the potential to demonstrate, by way of an inference- and science-based analysis, the causal relationship between chemical exposures, epigenome, and adverse health outcomes. Objective: The objective of this work is to discuss the epigenome as a modifier of exposure effects and risk, perspectives for integrating toxicoepigenetic data into an AOP framework, tools for the exploration of epigenetic toxicity, and integration of AOP-guided epigenetic information into science and risk-assessment processes. Discussion: Organizing epigenetic information into the topology of a qualitative AOP network may help describe how a system will respond to epigenetic modifications caused by environmental chemical exposures. However, understanding the biological plausibility, linking epigenetic effects to short- and long-term health outcomes, and including epigenetic studies in the risk assessment process is met by substantive challenges. These obstacles include understanding the complex range of epigenetic modifications and their combinatorial effects, the large number of environmental chemicals to be tested, and the lack of data that quantitatively evaluate the epigenetic effects of environmental exposure. Conclusion: We anticipate that epigenetic information organized into AOP frameworks can be consistently used to support biological plausibility and to identify data gaps that will accelerate the pace at which epigenetic information is applied in chemical evaluation and risk-assessment paradigms. https://doi.org/10.1289/EHP2322
Reply to Taimur T. Shah, Graeme MacLennan, Rob Pickard, Samuel McClinton and Veeru Kasivisvanathan's Letter to the Editor re: Zhangqun Ye, Guohua Zeng, Huan Yang, et al. Efficacy and Safety of Tamsulosin in Medical Expulsive Therapy for Distal Ureteral Stones with Renal Colic: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial. Eur Urol 2018;73:385–91
Authors: Zhangqun Ye, Guohua Zeng, Zhiqiang Chen, Hua Xu
Journal: European Urology (2018)
SHP-1 regulates hematopoietic stem cell quiescence by coordinating TGF-β signaling
Authors: Linjia Jiang, Xue Han, Jin Wang, Chen Wang, Xiaoqiang Sun, Jiayi Xie, Guojin Wu, Hiep Phan, Zhenguo Liu, Edward T.H. Yeh, ChengCheng Zhang, Meng Zhao, Xunlei Kang
Journal: The Journal of Experimental Medicine (2018)

Cell cycle quiescence is critical for hematopoietic stem cell (HSC) maintenance. TGF-β signaling in bone marrow niche has been identified in regulating HSC quiescence; however, the intrinsic regulatory mechanisms remain unclear. This study reports that Shp-1 knockout HSCs have attenuated quiescence and impaired long-term self-renewal. SHP-1–activated HSCs are surrounded by megakaryocytes, which regulate HSC quiescence by producing TGF-β1. Mechanistically, SHP-1 interacts with the immunoreceptor tyrosine-based inhibition motif on TGF-β receptor 1 and is critical for TGF-β signaling activation in HSCs. Functionally, Shp-1 knockout HSCs do not respond to TGF-β–enforced HSC quiescence regulation, both in vitro and in vivo. Therefore, we identify TGF-β–SHP-1 as a novel intrinsic regulatory mechanism for HSC quiescence maintenance.
Efficacy and safety of REGORAFENIB in real life in the treatment of hepatocellular carcinoma. Multicenter experience
Authors: M. Fraile, M.T. Ferrer, A.M. Matilla, J.L. Lledó, B. Minguez, A. Hernandez, C. Perelló, J. Fernández-Castroagudín, C.R. de Lope, M.D.E. Aguilar, S. Montoliu, M. Sala, M. Romero-Gutiérrez, S. Pascual, J.J. Urquijo, D.E.M. Arraez, M.J.B. Rodriguez, M. Varela
Journal: Journal of Hepatology (2018)
Letter by Mitchell et al Regarding Article, “Urinary Prostaglandin Metabolites: An Incomplete Reckoning and a Flush to Judgment”
Authors: Jane A. Mitchell, Rebecca B. Knowles, Nicholas S. Kirkby, Daniel M. Reed, Matthew L. Edin, William E. White, Melissa V. Chan, Hilary Longhurst, Magdi M. Yaqoob, Ginger L. Milne, Darryl C. Zeldin, Timothy D. Warner
Journal: Circulation Research (2018)
TCTAP A-153 Long-term Mortality of Vasospastic Angina Presented with ST-segment Depression on Electrocardiogram: Data form Asan Vasospastic Angina Registry
Authors: Hanbit Park, Sang Yong Om, Yong-Hoon Yoon, Minsoo Kim, Sang-Cheol Cho, Kyusup Lee, Osung Kwon, Do-Yoon Kang, Pil Hyung Lee, Jung-Min Ahn, Duk-Woo Park, Soo-Jin Kang, Seung-Whan Lee, Young-Hak Kim, Cheol Whan Lee, Seong-Wook Park, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2018)
How Many FOXs Are There on The Road to Pulmonary Hypertension?
Authors: Kurt R. Stenmark, Cheng-Jun Hu, Soni S. Pullamsetti
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

immune cells or from the tumor cells as well.Fourth, although there are clear differences in myeloid cells between patients and healthy control patients, there are some reservations as to the exact definition of these cells.It is largely accepted that the definition of MDSCs requires demonstration of T-cell suppression (10, 13), not shown in this study.The authors solely show expression of suppression markers, which though important, are only correlated to immunosuppressive capacity.This is especially problematic in light of the highly controversial issue regarding the definition of neutrophils versus 12).The data shown do not allow for clearly differentiating between these two cell types.Despite these limitations, the work of Yamauchi and colleagues is an important advancement and the beginning of "the next step" in understanding the immune response to lung cancer.Focusing on the role and effect of myeloid cells in lung cancer has the potential to assist in developing new diagnostic, prognostic, and possibly even therapeutic tools to combat this disease.