tbuckley/cabot-search huggingface dataset:
Effects of the Heartbeat Wales programme
Authors: S. Ebrahim, G. D. Smith, J. T. Hart, K. Harvey
Journal: BMJ (1998)

Editor—The Heartbeat Wales programme,1 in common with several other community health promotion projects that aim to reduce the risk of cardiovascular diseases,2 has reported no net changes in intervention compared with control regions. Tudor-Smith et al report these negative findings in an exemplary way, using a straightforward analysis.1 Their study concludes that more debate on the most appropriate methods of assessing the effectiveness of such programmes is needed. 

The investigators suggest that lack of power and contamination of the control region explain their failure to detect effects of the programme. The study had sufficient power to detect a 5% difference in prevalence between intervention and control regions. If the other community based interventions that were previously reviewed2 were included in a meta-analysis, the power would increase, but the lack of effect would still be apparent as these other programmes also had essentially negative results. 

Contamination of the control region is a possible explanation for the findings. Similar community health promotion programmes conducted from the 1970s to the 1990s have, however, reported consistent findings—no net difference in risk factors or clinical events attributable to the intervention. Moreover, the downward secular trends in mortality from cardiovascular disease in countries with diverging practices in health promotion suggests that these programmes are ineffective. 

The notion that alternative study designs can be found that will produce the right answer is fallacious. Quasi-experiments at community level and randomised controlled trials at the workplace, among families, or individual people show a consistency of small changes to the risk factor in effect only and no significant reduction in mortality.3 Similar interventions applied to populations at high risk (such as people with hypertension or pre-existing cardiovascular disease) are, however, effective.2 Consequently, health promotion programmes in their current form have only a limited potential for improving the health of the population. 

The response to rigorous evaluations that showed little or no added value of health promotion programmes for cardiovascular disease has been that either the design and execution of potentially misleading and methodologically flawed studies,4 for which exorbitant claims are made,5 or the methods are not appropriate in this situation. 

If more money is to be spent on research into health promotion an understanding of the effects of employment (changing socioeconomic position), food (pricing and availability), and transport (travel concessions) policies on health behaviours and risk factors would be a better investment than an attempt to shift the goalposts.
Abstract B21: Arylsulfatase B (ARSB) is reduced in melanoma metastases and decline in ARSB increases programmed death-ligand (PDL) 1
Authors: Joanne K. Tobacman, Sumit Bhattacharyya, Leo Feferman
Journal: Cancer Research (2020)

Abstract Arylsulfatase B (ARSB; N-acetylgalactosamine-4-sulfatase) is the enzyme that removes 4-sulfate groups from chondroitin 4-sulfate (C4S) and dermatan sulfate. In previous work, we have shown decline in ARSB with increasing aggressiveness of melanoma cell lines. C4S increased as ARSB declined in the cultured melanoma cell lines. Decline in ARSB was associated with increased expression of chondroitin sulfate proteoglycan (CSPG) 4 and matrix metalloproteinase (MMP) 2. The increase in CSPG4 was attributed to reduced binding of galectin-3 with C4S, and the increase of MMP2 was attributed to inhibition of SHP2, the tyrosine-protein phosphatase nonreceptor type 11 (PTPN11), due to increased binding with C4S. The invasiveness of the cultured melanoma cells increased when ARSB was silenced by siRNA. To further address the role of ARSB in melanoma progression, metastatic melanoma tissue was obtained from the biorepository of the University of Illinois at Chicago. ARSB activity and expression were reduced in the metastatic tissues and ARSB promoter methylation was increased. ARSB promoter methylation was also increased in cultured metastatic melanoma cells compared to normal melanocytes and to radial growth phase melanoma cells. In the metastatic tissues from skin and liver, SHP2 activity declined, and mRNA expression of MMP2 and CSPG4 increased. When ARSB was silenced by siRNA in the cultured normal melanocytes, Programmed Death-Ligand (PD-L) 1 increased from 78 ± 7 pg/mg protein to 128 ± 11 pg/mg protein by ELISA (p&amp;lt;0.001). In a metastatic melanoma cell line, PD-L1 increased from baseline value of 407 ± 34 pg/mg to 462 ± 26 pg/mg when ARSB was silenced. These findings indicate that decline in ARSB contributes to the progression of metastatic melanoma and to the immune checkpoint responsiveness of the melanoma cells. Further studies are required to determine how ARSB leads to increased PD-L1 expression and how treatment with recombinant ARSB can retard the progression of melanoma. Citation Format: Joanne K. Tobacman, Sumit Bhattacharyya, Leo Feferman. Arylsulfatase B (ARSB) is reduced in melanoma metastases and decline in ARSB increases programmed death-ligand (PDL) 1 [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr B21.
Plasma IL-6 changes correlate to PD-1 inhibitor responses in NSCLC
Authors: Alissa Keegan, Biagio Ricciuti, Padric Garden, Limor Cohen, Reiko Nishihara, Anika Adeni, Cloud Paweletz, Julianna Supplee, Pasi A Jänne, Mariano Severgnini, Mark M Awad, David R Walt
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Blood-based biomarkers of anti-solid tumor immune checkpoint blockade (ICB) response are lacking. We hypothesized that changes in systemic cytokine levels with the initial doses of programmed cell death protein 1 (PD-1) pathway inhibitors would correlate with clinical responses. New ultrasensitive ELISA technology enables quantitation of plasma proteins in sub-picogram-per-milliliter concentrations. Methods We measured plasma cytokines by ultrasensitive single-molecule array assays in patients with non-small-cell lung carcinoma before and during treatment with anti-PD-1 therapy. Association with best overall response and progression-free survival (PFS) was assessed by Kruskall-Wallis test and Kaplan-Meier plots with log-rank test, respectively. Results A decrease in interleukin 6 (IL-6) levels was associated with improved PFS (n=47 patients, median PFS: 11 vs 4 months, HR 0.45 (95% CI 0.23 to 0.89), p=0.04). The extent of change in IL-6 differed between best overall response categories (p=0.01) and correlated with changes in C reactive protein levels. We also explored plasma cytokine levels in relation to immune-related adverse effects and observed some correlation. Conclusions This study suggests the presence of a systemic, proteomic reflection of successful ICB outside the tumor microenvironment with plasma decreases in IL-6 and CRP.
Characteristics and Outcomes of Patients Deferred for Transcatheter Aortic Valve Replacement Because of COVID-19
Authors: Richard Ro, Sahil Khera, Gilbert H. L. Tang, Parasuram Krishnamoorthy, Samin K. Sharma, Annapoorna Kini, Stamatios Lerakis
Journal: JAMA Network Open (2020)

This cohort study examines the characteristics and outcomes of patients for whom transcatheter aortic valve replacement (TAVR) was deferred because of the coronavirus disease 2019 (COVID-19) pandemic.
Five-Year Outcomes With Nivolumab in Patients With Wild-Type <i>BRAF</i> Advanced Melanoma
Authors: Caroline Robert, Georgina V. Long, Benjamin Brady, Caroline Dutriaux, Anna Maria Di Giacomo, Laurent Mortier, Piotr Rutkowski, Jessica C. Hassel, Catriona M. McNeil, Ewa Anna Kalinka, Céleste Lebbé, Julie Charles, Micaela M. Hernberg, Kerry J. Savage, Vanna Chiarion-Sileni, Catalin Mihalcioiu, Cornelia Mauch, Ana Arance, Francesco Cognetti, Lars Ny, Henrik Schmidt, Dirk Schadendorf, Helen Gogas, Jesús Zoco, Sandra Re, Paolo A. Ascierto, Victoria Atkinson
Journal: Journal of Clinical Oncology (2020)

The CheckMate 066 trial investigated nivolumab monotherapy as first-line treatment for patients with previously untreated BRAF wild-type advanced melanoma. Five-year results are presented herein.In this multicenter, double-blind, phase III study, 418 patients with previously untreated, unresectable, stage III/IV, wild-type BRAF melanoma were randomly assigned 1:1 to receive nivolumab 3 mg/kg every 2 weeks or dacarbazine 1,000 mg/m2 every 3 weeks. The primary end point was overall survival (OS), and secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety.Patients were followed for a minimum of 60 months from the last patient randomly assigned (median follow-up, 32.0 months for nivolumab and 10.9 months for dacarbazine). Five-year OS rates were 39% with nivolumab and 17% with dacarbazine; PFS rates were 28% and 3%, respectively. Five-year OS was 38% in patients randomly assigned to dacarbazine who had subsequent therapy, including nivolumab (n = 37). ORR was 42% with nivolumab and 14% with dacarbazine; among patients alive at 5 years, ORR was 81% and 39%, respectively. Of 42 patients treated with nivolumab who had a complete response (20%), 88% (37 of 42) were alive as of the 5-year analysis. Among 75 nivolumab-treated patients alive and evaluable at the 5-year analysis, 83% had not received subsequent therapy; 23% were still on study treatment, and 60% were treatment free. Safety analyses were similar to the 3-year report.Results from this 5-year analysis confirm the significant benefit of nivolumab over dacarbazine for all end points and add to the growing body of evidence supporting long-term survival with nivolumab mono-therapy. Survival is strongly associated with achieving a durable response, which can be maintained after treatment discontinuation, even without subsequent systemic therapies.
Social license for the use of big data in the COVID-19 era
Authors: James A. Shaw, Nayha Sethi, Christine K. Cassel
Journal: npj Digital Medicine (2020)

Strategies to enable the reopening of businesses and schools in countries emerging from social-distancing measures revolve around knowledge of who has COVID-19 or is displaying recognized symptoms, the people with whom they have had physical contact, and which groups are most likely to experience adverse outcomes. Efforts to clarify these issues are drawing on the collection and use of large datasets about peoples' movements and their health. In this Comment, we outline the importance of earning social license for public approval of big data initiatives, and specify principles of data law and data governance practices that can promote social license. We provide illustrative examples from the United States, Canada, and the United Kingdom.
Planning for post‐pandemic cancer care delivery: Recovery or opportunity for redesign?
Authors: Pelin Cinar, Richard Bold, Bryn A. Bosslet, Daniela A. Bota, Debra Burgess, Helen K. Chew, Joshua G. Cohen, Emad Elquza, Kathryn A. Gold, Emi Kamiya, Beth Y. Karlan, Rana R. McKay, Sandip P. Patel, Kimberly Ternavan, Jeanna Welborn, Maki Yamamoto, Hope S. Rugo
Journal: CA A Cancer Journal for Clinicians (2020)

The delivery of cancer care has never changed as rapidly and dramatically as we have seen with the coronavirus disease 2019 (COVID-19) pandemic. During the early phase of the pandemic, recommendations for the management of oncology patients issued by various professional societies and government agencies did not recognize the significant regional differences in the impact of the pandemic. California initially experienced lower than expected numbers of cases, and the health care system did not experience the same degree of the burden that had been the case in other parts of the country. In light of promising trends in COVID-19 infections and mortality in California, by late April 2020, discussions were initiated for a phased recovery of full-scale cancer services. However, by July 2020, a surge of cases was reported across the nation, including in California. In this review, the authors share the response and recovery planning experience of the University of California (UC) Cancer Consortium in an effort to provide guidance to oncology practices. The UC Cancer Consortium was established in 2017 to bring together 5 UC Comprehensive Cancer Centers: UC Davis Comprehensive Cancer Center, UC Los Angeles Jonsson Comprehensive Cancer Center, UC Irvine Chao Family Comprehensive Cancer Center, UC San Diego Moores Cancer Center, and the UC San Francisco Helen Diller Family Comprehensive Cancer Center. The interventions implemented in each of these cancer centers are highlighted, with a focus on opportunities for a redesign in care delivery models. The authors propose that their experiences gained during this pandemic will enhance pre-pandemic cancer care delivery.
The association of IL28B genotype with peginterferon-alpha/ribavirin ( PR) treatment outcome and liver interferon-stimulated gene (ISG) expression is determined by HCV genotype
Authors: Jacinta A Holmes, Mario Congiu, Sara Bonanazinga, Manjeet K Sandhu, Yin H Kia, Sally Bell, Kumar Visvanathan, William Sievert, Scott Bowden, Paul V Desmond, Alexander J Thompson
Journal: Hepatology (2012)
Five-Year Outcomes of Endoscopic Sleeve Gastroplasty for the Treatment of Obesity
Authors: Reem Z. Sharaiha, Kaveh Hajifathalian, Rekha Kumar, Katherine Saunders, Amit Mehta, Bryan Ang, Daniel Skaf, Shawn Shah, Andrea Herr, Leon Igel, Qais Dawod, Enad Dawod, Kartik Sampath, David Carr-Locke, Robert Brown, David Cohen, Andrew J. Dannenberg, Srihari Mahadev, Alpana Shukla, Louis J. Aronne
Journal: Clinical Gastroenterology and Hepatology (2020)
Post-Thoracoscopy Lung Re-Expansion: Pilot Data Using Digital Suction Device
Authors: R J Hallifax, J P Corcoran, N M Rahman
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Introduction  Current practice for diagnostic only thoracoscopy varies from day-case procedures to routine overnight stays. Radiographic evidence of lung re-expansion and underwater seal evidence of lack of on-going air leak are required before patient discharge. Use of a digital suction device which accurately measures air leak may allow earlier identification of lung re-expansion and hence earlier discharge.  Patients pleurodesed at thoracoscopy are admitted for 3–4 days, however the presence of trapped lung preventing re-expansion after thoracoscopy reduces the chance of successful pleurodesis, and measurement of air leak with a digital device may allow prediction of trapped lung.  Aim  To determine whether initial air leak measurement can predict trapped lung and whether use of digital device can reduce time to chest radiograph post thoracoscopy.  Methods  Data was prospectively collected (November 2012 to May 2013), on patients undergoing thoracoscopy in a specialist respiratory centre. Post-procedure, the “air leak” was measured using a digital suction device (Thopaz, Medela UK), and time to chest radiograph (CXR) was compared to LAT in the preceding three months.  Results  32 patients were investigated. Results were non-normally distributed so non-parametric analysis was undertaken. Median initial flow rate post-thoracoscopy was 108ml/min. Nine (28%) had trapped lung: median air flow rate was significantly lower in this group 45ml/min (IQR 39–118ml/min) vs 118ml/min (IQR 75–179ml/min), using Mann-Whitney U Test (p = 0.01). Those with trapped lung had larger effusions drained during procedure: 1739ml vs 1332ml (p = 0.48).  Fourteen (44%) patients were successfully managed as day-cases with the digital suction device: mean time to CXR was 2.1 hours (SD 1.1); less than the 8 preceding day-case thoracoscopies (mean 2.9, SD 1.6 hours) (p = 0.2).  Conclusion  This pilot data suggests that digital air flow measurement has the potential to predict which patients are likely to have trapped lung and lack of air leak, and may potentially identify the group of patients in which to use indwelling pleural catheters. Use of the device may also allow earlier identification of full re-expansion, earlier CXR and hence more rapid discharge home.
Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL
Authors: Andreas Agathangelidis, Anastasia Chatzidimitriou, Katerina Gemenetzi, Veronique Giudicelli, Maria Karypidou, Karla Plevova, Zadie Davis, Xiao-Jie Yan, Sabine Jeromin, Christof Schneider, Lone Bredo Pedersen, Renee C. Tschumper, Lesley-Ann Sutton, Panagiotis Baliakas, Lydia Scarfò, Ellen J. van Gastel, Marine Armand, Eugen Tausch, Bella Biderman, Constance Baer, Davide Bagnara, Alba Navarro, Anne Langlois de Septenville, Valentina Guido, Gerlinde Mitterbauer-Hohendanner, Aleksandar Dimovski, Christian Brieghel, Sarah Lawless, Manja Meggendorfer, Kamila Brazdilova, Matthias Ritgen, Monica Facco, Cristina Tresoldi, Andrea Visentin, Andrea Patriarca, Mark Catherwood, Lisa Bonello, Andrey Sudarikov, Katrina Vanura, Maria Roumelioti, Hana Skuhrova Francova, Theodoros Moysiadis, Silvio Veronese, Krzysztof Giannopoulos, Larry Mansouri, Teodora Karan-Djurasevic, Raphael Sandaltzopoulos, Csaba Bödör, Franco Fais, Arnon Kater, Irina Panovska, Davide Rossi, Salem Alshemmari, Panagiotis Panagiotidis, Paul Costeas, Blanca Espinet, Darko Antic, Letizia Foroni, Marco Montillo, Livio Trentin, Niki Stavroyianni, Gianluca Gaidano, Paola Francia di Celle, Carsten Niemann, Elias Campo, Achilles Anagnostopoulos, Christiane Pott, Kirsten Fischer, Michael Hallek, David Oscier, Stephan Stilgenbauer, Claudia Haferlach, Diane Jelinek, Nicholas Chiorazzi, Sarka Pospisilova, Marie-Paule Lefranc, Sofia Kossida, Anton W. Langerak, Chrysoula Belessi, Frederic Davi, Richard Rosenquist, Paolo Ghia, Kostas Stamatopoulos
Journal: Blood (2020)
Contrasting Gene Decay in Subterranean Vertebrates: Insights from Cavefishes and Fossorial Mammals
Authors: Maxime Policarpo, Julien Fumey, Philippe Lafargeas, Delphine Naquin, Claude Thermes, Magali Naville, Corentin Dechaud, Jean-Nicolas Volff, Cedric Cabau, Christophe Klopp, Peter Rask Møller, Louis Bernatchez, Erik García-Machado, Sylvie Rétaux, Didier Casane
Journal: Molecular Biology and Evolution (2020)

Evolution sometimes proceeds by loss, especially when structures and genes become dispensable after an environmental shift relaxes functional constraints. Subterranean vertebrates are outstanding models to analyze this process, and gene decay can serve as a readout. We sought to understand some general principles on the extent and tempo of the decay of genes involved in vision, circadian clock, and pigmentation in cavefishes. The analysis of the genomes of two Cuban species belonging to the genus Lucifuga provided evidence for the largest loss of eye-specific genes and nonvisual opsin genes reported so far in cavefishes. Comparisons with a recently evolved cave population of Astyanax mexicanus and three species belonging to the Chinese tetraploid genus Sinocyclocheilus revealed the combined effects of the level of eye regression, time, and genome ploidy on eye-specific gene pseudogenization. The limited extent of gene decay in all these cavefishes and the very small number of loss-of-function mutations per pseudogene suggest that their eye degeneration may not be very ancient, ranging from early to late Pleistocene. This is in sharp contrast with the identification of several vision genes carrying many loss-of-function mutations in ancient fossorial mammals, further suggesting that blind fishes cannot thrive more than a few million years in cave ecosystems.
Indications for Total Gastrectomy in <i>CDH1</i> Mutation Carriers and Outcomes of Risk-Reducing Minimally Invasive and Open Gastrectomies
Authors: Elvira L. Vos, Erin E. Salo-Mullen, Laura H. Tang, Mark Schattner, Sam S. Yoon, Hans Gerdes, Arnold J. Markowitz, Diana Mandelker, Yelena Janjigian, Kenneth Offitt, Daniel G. Coit, Zsofia K. Stadler, Vivian E. Strong
Journal: JAMA Surgery (2020)

CDH1 variants are increasingly identified on commercially available multigene panel tests, calling for data to inform counseling of individuals without a family history of gastric cancer.To assess association between CDH1 variant pathogenicity or family history of gastric or lobular breast cancer and identification of signet ring cell cancer and to describe outcomes of risk-reducing minimally invasive and open total gastrectomy.This cohort study was performed from January 1, 2006, to January 1, 2020, in 181 patients with CDH1 germline variants from a single institution.Genetic counseling, esophagogastroduodenoscopy, and possible total gastrectomy.CDH1 variant classification, family cancer history, findings of signet ring cell carcinoma at esophagogastroduodenoscopy and surgery, postoperative events and weight changes, and follow-up.Of 181 individuals with CDH1 germline variants (mean [SD] age at time of testing, 44 [15] years; 126 [70%] female), 165 harbored a pathogenic or likely pathogenic variant. Of these patients, 101 underwent open (n = 58) or minimally invasive (n = 43) total gastrectomy. Anastomotic leaks that required drainage were infrequent (n = 3), and median long-term weight loss was 20% (interquartile range [IQR], 10%-23%). In those undergoing minimally invasive operations, more lymph nodes were retrieved (median, 28 [IQR, 20-34] vs 15 [IQR, 9-19]; P < .001) and the hospital stay was 1 day shorter (median, 6 [IQR, 5-7] vs 7 [IQR, 6-7] days; P = .04). Signet ring cell cancer was identified in the surgical specimens of 85 of 95 patients (89%) with a family history of gastric cancer and 4 of 6 patients (67%) who lacked a family history. Among the latter 6 patients, 4 had a personal or family history of lobular breast cancer, including 2 with signet ring cell cancer. Of the 16 patients with pathogenic or likely pathogenic CDH1 variants who presented with locally advanced or metastatic gastric cancer, 3 (19%) had no family history of gastric cancer or personal or family history of lobular breast cancer.Total gastrectomy may be warranted for patients with pathogenic or likely pathogenic CDH1 variants and a family history of gastric or lobular breast cancer and may be appropriate for those without a family history. A minimally invasive approach is feasible and may be preferred for selected patients.
MEDICAL EDUCATION IN MEXICO.
Authors: C ZUCKERMANN
Journal: JAMA (1998)

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