tbuckley/cabot-search huggingface dataset:
Open notes: A qualitative study of oncology patients’ experiences reading their cancer care notes.
Authors: Neha Kayastha, Kathryn I. Pollak, Thomas William LeBlanc
Journal: Journal of Clinical Oncology (2017)

33 Background: Electronic medical record systems and patient portals increasingly allow patients direct access to their clinicians’ notes.While most believe that open notes benefit patients, some suggest negative consequences. Little is known about cancer patients’ experiences reading their own medical records outside of the primary care setting. We aimed to describe the experiences of patients with advanced cancer who read their own cancer care notes. Methods: We recruited 20 adult patients with metastatic or incurable cancer who were receiving active cancer treatment to participate in semi-structured qualitative interviews. The interview included four segments: assessing patients' overall experience reading notes, discussing how notes affected their cancer care experiences, having them read a real note with the interviewer, and making suggestions for improving notes. We used a constant comparison approach to analyze the qualitative data. Results: Four main themes emerged; patients reported that notes: (a) increased comprehension, (b) ameliorated uncertainty, relieved anxiety, and facilitated control, (c) increased trust, and (d) for a subset, increased anxiety. Patients described increased comprehension, as notes refreshed their memory and clarified their understanding of visits. Notes addressed uncertainty and relieved anxiety, in part because enhanced comprehension mitigated the unfamiliarity of cancer. They facilitated control, empowering patients to ask more questions to clinicians. The transparency of notes also increased the trust patients have in their clinicians. For a subset of patients, however, notes were emotionally difficult to read and raised concerns. Patients consistently identified medical jargon and repetition in notes as areas for improvement. Conclusions: Our findings suggest that most patients felt that reading notes improved their care experiences. A small subset experienced increased distress from “open notes.” As reading notes becomes a routine part of the patient experience, it is important for physicians to elicit and address concerns that arise from the notes, further engaging patients in their care.
Immature CML cells implement a BMP autocrine loop to escape TKI treatment
Authors: Elodie Grockowiak, Bastien Laperrousaz, Sandrine Jeanpierre, Thibault Voeltzel, Boris Guyot, Stéphanie Gobert, Franck E. Nicolini, Véronique Maguer-Satta
Journal: Blood (2017)
Tuberculosis patients with unknown HIV status in the Netherlands: analysing underreporting and lack of testing
Authors: Maike Arnoldussen, Henrieke Schimmel, Eline Op de Coul, Susan van den Hof, Gerard de Vries
Journal: European Respiratory Journal (2017)

The epidemics of tuberculosis (TB) and HIV are closely linked, as HIV infection is the main risk factor for progression from latent TB infection to active TB disease [1]. Globally, 11% of the 10.4 million new TB cases in 2015 were HIV-infected, and 22% of the 1.8 million TB deaths were among HIV-infected patients [2]. Despite all efforts made by collaborative TB/HIV programmes, less than half of all TB patients worldwide are estimated to be tested for HIV infection [2, 3]. Only 19 of the 31 countries, representing a third of all TB patients in the European Union (EU) and European Economic Area (EEA), report HIV status, with 67.6% of patients in these countries having a known HIV status [4]. Better information on the burden of TB/HIV co-infections will aid the planning and evaluation of TB/HIV prevention and control activities in various countries [5–8]. Few HIV-co-infected TB patients are missed despite suboptimal testing and reporting in the Netherlands <http://ow.ly/VT9230fPJpi> The authors would like to thank the public health nurses and physicians of the TB departments of the Municipal Public Health Services who participated in this study.
YAP1 and COX2 Coordinately Regulate Urothelial Cancer Stem-like Cells
Authors: Akira Ooki, Maria Del Carmen Rodriguez Pena, Luigi Marchionni, Wikum Dinalankara, Asma Begum, Noah M. Hahn, Christopher J. VandenBussche, Zeshaan A. Rasheed, Shifeng Mao, George J. Netto, David Sidransky, Mohammad O. Hoque
Journal: Cancer Research (2017)

Overcoming acquired drug resistance remains a core challenge in the clinical management of human cancer, including in urothelial carcinoma of the bladder (UCB). Cancer stem-like cells (CSC) have been implicated in the emergence of drug resistance but mechanisms and intervention points are not completely understood. Here, we report that the proinflammatory COX2/PGE2 pathway and the YAP1 growth-regulatory pathway cooperate to recruit the stem cell factor SOX2 in expanding and sustaining the accumulation of urothelial CSCs. Mechanistically, COX2/PGE2 signaling induced promoter methylation of let-7, resulting in its downregulation and subsequent SOX2 upregulation. YAP1 induced SOX2 expression more directly by binding its enhancer region. In UCB clinical specimens, positive correlations in the expression of SOX2, COX2, and YAP1 were observed, with coexpression of COX2 and YAP1 particularly commonly observed. Additional investigations suggested that activation of the COX2/PGE2 and YAP1 pathways also promoted acquired resistance to EGFR inhibitors in basal-type UCB. In a mouse xenograft model of UCB, dual inhibition of COX2 and YAP1 elicited a long-lasting therapeutic response by limiting CSC expansion after chemotherapy and EGFR inhibition. Our findings provide a preclinical rationale to target these pathways concurrently with systemic chemotherapy as a strategy to improve the clinical management of UCB.Significance: These findings offer a preclinical rationale to target the COX2 and YAP1 pathways concurrently with systemic chemotherapy to improve the clinical management of UCB, based on evidence that these two pathways expand cancer stem-like cell populations that mediate resistance to chemotherapy. Cancer Res; 78(1); 168-81. ©2017 AACR.
Long-term effects of glucocorticoids on function, quality of life, and survival in patients with Duchenne muscular dystrophy: a prospective cohort study
Authors: Craig M McDonald, Erik K Henricson, Richard T Abresch, Tina Duong, Nanette C Joyce, Fengming Hu, Paula R Clemens, Eric P Hoffman, Avital Cnaan, Heather Gordish-Dressman, Vijay Vishwanathan, S Chidambaranathan, W. Douglas Biggar, Laura C. McAdam, Jean K. Mah, Mar Tulinius, Avital Cnaan, Lauren P. Morgenroth, Robert Leshner, Carolina Tesi-Rocha, Mathula Thangarajh, Tina Duong, Andrew Kornberg, Monique Ryan, Yoram Nevo, Alberto Dubrovsky, Paula R. Clemens, Hoda Abdel-Hamid, Anne M. Connolly, Alan Pestronk, Jean Teasley, Tulio E. Bertorin, Richard Webster, Hanna Kolski, Nancy Kuntz, Sherilyn Driscoll, John B. Bodensteiner, Jose Carlo, Ksenija Gorni, Timothy Lotze, John W. Day, Peter Karachunski, Erik K. Henricson, Richard T. Abresch, Nanette C. Joyce, Craig M. McDonald
Journal: The Lancet (2017)
Risk factors and prophylaxis of irinotecan induced cholinergic syndrome in sight of supportive care.
Authors: Hiroyuki Fujii, Taizo Hirata, Takuya Mura, Yuko Okada, Takuo Ito, Shinji Ozaki, Hirotaka Tashiro, Tomoya Mizunoe, Hiroshi Kohno, Kikuo Nakano
Journal: Journal of Clinical Oncology (2017)

216 Background: Irinotecan Induced Cholinergic Syndrome (IICS), manifesting in such events as early diarrhea and diaphoresis, is well-known adverse effect of irinotecan. These symptoms occur within the first 24 hours of irinotecan administration and can be ameliorated with anticholinergic agents. Although IICS is transient and tends to be underestimated, diarrhea and abdominal pain during drug infusion are inflictive and make patients reluctant to undergo anticancer therapy. Methods: First, to identify the risk factors that are associated with IICS, 132 consecutive patients who were treated with a chemotherapeutic regimen that included irinotecan at Kure Medical Center between 2012 and 2017 were retrospectively analyzed from the aspect of sex, age, dose, cancer type, regimen, kidney function, and renal function. Secondly, to determine the response rate of butylscopolamine bromide for IICS, we injected butylscopolamine bromide 20mg into the irinotecan infusion bag and administered both agents through the intravenous line together to patients who experienced IICS. Results: IICS occurred 14 of 132 patients (10.6%); these 14 patients were given butylscopolamine bromide by coinjection for total 119 cycles. Univariate analysis indicated that dose (p = 0.0029), cancer type (p = 0.0023) and regimen (p = 0.0005) was associated with IICS. Patients with symptoms tended to be administered a higher irinotecan dose than those without symptoms (127.9±20.4mg/m 2 and 99.6±34.1mg/m 2 ). By logistic regression analysis, a higher dose (dose &gt; 105mg/m 2 ) was identified a significant risk factor for IICS (Odds Ratio = 10.9; 95% Confidence Interval: 2.0 to 96.7; p = 0.0121). 13 patients (105 cycles) of 14 patients (119 cycles) who were administered butylscopolamine bromide, experienced complete or partial improvement of IICS. The response rate was nearly 90%. Conclusions: A higher dose of irinotecan is a significant risk factor for IICS. To avoid creating a disincentive for patients to undergo anticancer therapy, the prevention of IICS is paramount. As prophylaxis of IICS, mixing butylscopolamine bromide into the irinotecan infusion bag was remarkably effective.
Should we focus on the fight against achalasia or equivocal results of reflux after peroral endoscopic myotomy?
Authors: Nikolas Eleftheriadis
Journal: Endoscopy (2017)

See also: Gastroesophageal reflux after peroral endoscopic myotomy: a multicenter case–control studyEndoscopy 2017; 49(07): 634-642DOI: 10.1055/s-0043-105485 See also: Reply to Eleftheriadis and to Sharma et al.Endoscopy 2017; 49(12): 1284-1284DOI: 10.1055/s-0043-122071
Recurrent de novo mutations in neurodevelopmental disorders: properties and clinical implications
Authors: Amy B. Wilfert, Arvis Sulovari, Tychele N. Turner, Bradley P. Coe, Evan E. Eichler
Journal: Genome Medicine (2017)

Next-generation sequencing (NGS) is now more accessible to clinicians and researchers. As a result, our understanding of the genetics of neurodevelopmental disorders (NDDs) has rapidly advanced over the past few years. NGS has led to the discovery of new NDD genes with an excess of recurrent de novo mutations (DNMs) when compared to controls. Development of large-scale databases of normal and disease variation has given rise to metrics exploring the relative tolerance of individual genes to human mutation. Genetic etiology and diagnosis rates have improved, which have led to the discovery of new pathways and tissue types relevant to NDDs. In this review, we highlight several key findings based on the discovery of recurrent DNMs ranging from copy number variants to point mutations. We explore biases and patterns of DNM enrichment and the role of mosaicism and secondary mutations in variable expressivity. We discuss the benefit of whole-genome sequencing (WGS) over whole-exome sequencing (WES) to understand more complex, multifactorial cases of NDD and explain how this improved understanding aids diagnosis and management of these disorders. Comprehensive assessment of the DNM landscape across the genome using WGS and other technologies will lead to the development of novel functional and bioinformatics approaches to interpret DNMs and drive new insights into NDD biology.
Free cholesterol accumulation in liver sinusoidal endothelial cells exacerbates acetaminophen hepatotoxicity in mice
Authors: T. Teratani, K. Tomita, T. Suzuki, H. Furuhashi, R. Irie, S. Hida, Y. Okada, C. Kurihara, H. Ebinuma, N. Nakamoto, H. Saito, T. Hibi, S. Miura, R. Hokari, T. Kanai
Journal: Journal of Hepatology (2017)
Adaptation of the ASSIST peer-led smoking intervention to deliver information from the Talk to FRANK drug education website (ASSIST+FRANK): a pilot cluster-randomised controlled trial
Authors: James White, Jemma Hawkins, Kim Madden, Aimee Grant, Vanessa Er, Lianna Angel, Timothy Pickles, Mark Kelson, Adam Fletcher, Simon Murphy, Luke Midgley, Gemma Eccles, Gemma Cox, William Hollingworth, Rona Campbell, Matt Hickman, Chris Bonell, Laurence Moore
Journal: The Lancet (2017)
Eradication of Helicobacter pylori does not reduce the incidence of gastroduodenal ulcers in patients on long-term NSAID treatment: A randomized, double blind placebo controlled trial
Authors: Htji De Leest, K.S.S. Steen, W.F. Lems, P.J. Kostense, Mafj Van de Laar, AM de Roda Husman, Jwj Bijlsma, H.H.M.L. Houben, S.W. Kadir, E.J. Kuipers, MW Van Tulder, M Boers, B.A.C. Dijkmans
Journal: Annals of the Rheumatic Diseases (2004)
Exposure to Perfluoroalkyl Substances and Metabolic Outcomes in Pregnant Women: Evidence from the Spanish INMA Birth Cohorts
Authors: Nuria Matilla-Santander, Damaskini Valvi, Maria-Jose Lopez-Espinosa, Cyntia B. Manzano-Salgado, Ferran Ballester, Jesús Ibarluzea, Loreto Santa-Marina, Thomas Schettgen, Mònica Guxens, Jordi Sunyer, Martine Vrijheid
Journal: Environmental Health Perspectives (2017)

Exposure to perfluoroalkyl substances (PFASs) may increase risk for metabolic diseases; however, epidemiologic evidence is lacking at the present time. Pregnancy is a period of enhanced tissue plasticity for the fetus and the mother and may be a critical window of PFAS exposure susceptibility.We evaluated the associations between PFAS exposures and metabolic outcomes in pregnant women.We analyzed 1,240 pregnant women from the Spanish INMA [Environment and Childhood Project (INfancia y Medio Ambiente)] birth cohort study (recruitment period: 2003-2008) with measured first pregnancy trimester plasma concentrations of four PFASs (in nanograms/milliliter). We used logistic regression models to estimate associations of PFASs (log10-transformed and categorized into quartiles) with impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM), and we used linear regression models to estimate associations with first-trimester serum levels of triglycerides, total cholesterol, and C-reactive protein (CRP).Perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) were positively associated with IGT (137 cases) [OR per log10-unit increase=1.99 (95% CI: 1.06, 3.78) and OR=1.65 ( 95% CI: 0.99, 2.76), respectively]. PFOS and PFHxS associations with GDM (53 cases) were in a similar direction, but less precise. PFOS and perfluorononanoate (PFNA) were negatively associated with triglyceride levels [percent median change per log10-unit increase=-5.86% (95% CI: -9.91%, -1.63%) and percent median change per log10-unit increase=-4.75% (95% CI: -8.16%, -0.61%, respectively], whereas perfluorooctanoate (PFOA) was positively associated with total cholesterol [percent median change per log10-unit increase=1.26% (95% CI: 0.01%, 2.54%)]. PFASs were not associated with CRP in the subset of the population with available data (n=640).Although further confirmation is required, the findings from this study suggest that PFAS exposures during pregnancy may influence lipid metabolism and glucose tolerance and thus may impact the health of the mother and her child. https://doi.org/10.1289/EHP1062.
New flow cytometric procedure for the analysis of drug effects on topoisomerase II-DNA binding
Authors: Ikuo Wada, James Mittler, Robert M. Snapka, Igor B. Roninson, Eugenia V. Broude
Journal: Cancer Research (2005)

3968   Topoisomerase II (Topo II) is the target of many clinically important antitumor drugs. The best-known drugs of this class are known as Topo II poisons, which stabilize cleavable complexes of Topo II covalently linked to DNA. Other Topo II inhibitors, usually categorized as catalytic inhibitors, affect other steps in Topo II-catalyzed DNA decatenation. Topo II poisons are generally identified through biochemical assays, by their ability to increase Topo II cleavable complex formation. These cell-free assays are laborious, require a large amount of material, and do not identify other types of Topo II inhibitors. We have developed a new rapid assay for agents that increase Topo II-DNA association in situ, based on flow cytometric analysis of the retention of a Topo II-GFP fusion protein in the nuclei of permeabilized cells. GFP fusions of the wild-type Topo IIα and its non-functional mutant (gifts of Dr. W.T. Beck) were stably transfected into a derivative of 293 cells, a transformed human embryonic kidney cell line. Cells were treated with 0.05% Triton X-100 and GFP fluorescence of permeabilized nuclei was analyzed by FACS. Wild type Topo II-GFP was retained much more efficiently than the mutant Topo II-GFP, indicating that Topo II-GFP retention reflected functional Topo II-DNA interactions. We have used this assay to analyze the effects of 20-minute exposure to different types of Topo II inhibitors and topoisomerase I inhibitor camptothecin. Topo II-GFP retention was unaffected by camptothecin but increased by most of the tested Topo II inhibitors. In contrast, Topo II inhibitors had no effect on the retention of the Topo II mutant. The strongest increase in Topo II-GFP retention was observed with classical Topo II poisons, teniposide and etoposide, as well as with bisdioxopiperazine derivatives (ICRF-193 and MST-16), recently shown to constitute a different class of Topo II poisons. One of the tested catalytic inhibitors, merbarone, also increased Topo II-GFP retention, albeit to a lesser degree than the Topo II poisons, whereas another catalytic inhibitor (novobiocin) had no effect. These results confirm Topo II-DNA complex stabilization by bisdioxopiperazines and reveal important differences in the effects of catalytic inhibitors on Topo II-DNA interaction. In contrast to the biochemical assays for Topo II-DNA binding, our method rapidly measures such interactions in situ, requires a small amount of material, does not use radioactive materials, and can detect both covalent and non-covalent Topo II-DNA interactions. This method should be useful both for mechanistic analysis and for de novo identification of Topo II-targeting compounds. This study is supported by NIH Grants RO1 CA95727 (I.B.R.) and RO1 CA97107 (R.M.S.).
Chemotherapy-Free Induction with Ibrutinib-Rituximab Followed By Shortened Cycles of Chemo-Immunotherapy Consolidation in Young, Newly Diagnosed Mantle Cell Lymphoma Patients: A Phase II Clinical Trial
Authors: Michael Wang, Hun Ju Lee, Selvi Thirumurthi, Hubert H Chuang, Fredrick B. Hagemeister, Jason R. Westin, Luis E. Fayad, Felipe Samaniego, Francesco Turturro, Wendy Chen, Onyeka Oriabure, Steven Y Huang, Shaoying Li, Liang Zhang, Maria Badillo, Kimberly H Hartig, Makhdum Ahmed, Krystle Nomie, Laura T Lam, Alicia A Addison, Jorge E. Romaguera
Journal: Blood (2016)
Enhancement of radiotherapy in prostate cancer by the novel dibenzo(c)chromen-6-one derivate Palomid 529
Authors: Roque Diaz, Paul Nguewa, Juan Diaz-Gonzalez, Diego Serrano, Oscar Gonzalez, Celia Prior, Miriam Redrado, Raul Catena, David Sherris, Alfonso Calvo
Journal: Cancer Research (2008)

4820   Radiotherapy (RT) is a common treatment for localized prostate cancer, but can cause important side effects. The therapeutic effect of RT can be enhanced by pharmacological compounds that target specific pathways involved in cell survival. This would elicit a similar therapeutic response using lower doses of RT and, in turn, reducing side effects. We have used the novel dibenzo(c)chromen-6-one (DBC) derivate P529 in combination with RT in PC-3 cells, in vitro and in vivo (in xenograft models). P529 alone produced cytotoxicity in PC-3 cells (IC50= 3 microM). Treatment of PC-3 cells with P529 and RT caused a dramatic decrease in phospho-AKT, VEGF and Id-1. The ratio Bcl2/Bax was also reduced. Doses of 2, 4, and 8 Gy produced 22.3%, 33.4%, 62.3% cell growth inhibition, respectively. Combination of 2μM P529 with 2 Gy RT produced 78.9% growth inhibition. In vivo studies in nude mice xenotransplanted with PC-3 cells and treated with 50 mg/Kg P529 (3 times a week) for 3 weeks, 6 Gy radiotherapy, or combination, resulted in the following tumor volume decrease (as compared to controls): 42.5%, 52.3%, and 76.3% (p=0.005), respectively. Tumors receiving combination therapy showed massive necrotic, apoptotic and fibrotic areas. Proliferation rates in tumours were significantly reduced, as a result of the treatment. Our results demonstrate that the dibenzo(c)chromen-6-one derivate P529 significantly enhances the effect of radiotherapy in prostate cancer.
A systematic and objective method in droplet gating analysis of EGFR T790M mutation on the ultra-sensitive droplet digital PCR (ddPCR) platform
Authors: C.H. Loh, G.L.X. Toh, C.W. Lim, W.C. Sim, C.M. Yeo, A. Chopra, L.L. Goh
Journal: Annals of Oncology (2017)
Phase II study of efficacy of bevacizumab plus chemotherapy in management of malignant pleural effusion in non-squamous non-small cell lung cancer patients with malignant pleural effusion (MPE) unsuccessfully controlled by tube drainage or pleurodesis (NEJ-13-2 trial)
Authors: R. Noro, K. Kobayashi, J. Usuki, Y. Hosomi, M. Nishitsuji, H. Okamoto, M. Ando, M. Hino, K. Hagiwara, A. Miyanaga, M. Seike, K. Kubota, A. Gemma
Journal: Annals of Oncology (2017)
The UMOD Locus: Insights into the Pathogenesis and Prognosis of Kidney Disease
Authors: Olivier Devuyst, Cristian Pattaro
Journal: Journal of the American Society of Nephrology (2017)

The identification of genetic factors associated with kidney disease has the potential to provide critical insights into disease mechanisms. Genome-wide association studies have uncovered genomic regions associated with renal function metrics and risk of CKD. UMOD is among the most outstanding loci associated with CKD in the general population, because it has a large effect on eGFR and CKD risk that is consistent across different ethnic groups. The relevance of UMOD for CKD is clear, because the encoded protein, uromodulin (Tamm–Horsfall protein), is exclusively produced by the kidney tubule and has specific biochemical properties that mediate important functions in the kidney and urine. Rare mutations in UMOD are the major cause of autosomal dominant tubulointerstitial kidney disease, a condition that leads to CKD and ESRD. In this brief review, we use the UMOD paradigm to describe how population genetic studies can yield insight into the pathogenesis and prognosis of kidney diseases.
Outcomes and predictive markers of trastuzumab-containing 1st-line chemotherapy in patients with HER2-positive advanced gastric cancer
Authors: J. Cheon, M-H Ryu, S.R. Park, B-Y Ryoo, J. Jeong, J.H. Park, B. Kim, Y. Park, Y-K Kang
Journal: Annals of Oncology (2017)