tbuckley/cabot-search huggingface dataset:
Effect of Public Deliberation on Patient Attitudes Regarding Consent and Data Use in a Learning Health Care System for Oncology
Authors: Reshma Jagsi, Kent A. Griffith, Rochelle D. Jones, Chris Krenz, Michele Gornick, Rebecca Spence, Raymond De Vries, Sarah T. Hawley, Robin Zon, Sage Bolte, Navid Sadeghi, Richard L. Schilsky, Angela R. Bradbury
Journal: Journal of Clinical Oncology (2019)

PURPOSE We sought to generate informed and considered opinions regarding acceptable secondary uses of deidentified health information and consent models for oncology learning health care systems. METHODS Day-long democratic deliberation sessions included 217 patients with cancer at four geographically and sociodemographically diverse sites. Patients completed three surveys (at baseline, immediately after deliberation, and 1-month follow-up). RESULTS Participants were 67.3% female, 21.7% black, and 6.0% Hispanic. The most notable changes in perceptions after deliberation related to use of deidentified medical-record data by insurance companies. After discussion, 72.3% of participants felt comfortable if the purpose was to make sure patients receive recommended care ( v 79.5% at baseline; P = .03); 24.9% felt comfortable if the purpose was to determine eligibility for coverage or reimbursement ( v 50.9% at baseline; P &lt; .001). The most notable change about secondary research use related to believing it was important that doctors ask patients at least once whether researchers can use deidentified medical-records data for future research. The proportion endorsing high importance decreased from baseline (82.2%) to 68.7% immediately after discussion ( P &lt; .001), and remained decreased at 73.1% ( P = .01) at follow-up. At follow-up, non-Hispanic whites were more likely to consider it highly important to be able to conduct medical research with deidentified electronic health records (96.8% v 87.7%; P = .01) and less likely to consider it highly important for doctors to get a patient’s permission each time deidentified medical record information is used for research (23.2% v 51.6%; P &lt; .001). CONCLUSION This research confirms that most patients wish to be asked before deidentified medical records are used for research. Policies designed to realize the potential benefits of learning health care systems can, and should be, grounded in informed and considered public opinion.
Prognostic immunoprofiling of muscle invasive bladder cancer (MIBC) patients in a multicentre setting
Authors: K. Nekolla, N. Brieu, C.G. Gavriel, M. Widmaier, A. Budco, D. Medrikova, I. Kanchev, M. Testori, J. Chan, P. Dundee, P. Anderson, N. Lawrentschuk, L.-M. Wong, P. Phan, P. Gibbs, D.J. Harrison, M. Baehner, P.D. Caie, B. Tran, G. Schmidt
Journal: Annals of Oncology (2019)
Association between serum HGF levels and neutrophil counts in small cell lung cancer and their impact on survival
Authors: L. Moliner, M. Hardy-Werbin, X. Duran, O. Arpí, Á Taus, P. Rocha, R. Del Rey, M.A. Galindo-Campos, A. Rovira, J. Albanell, E. Arriola
Journal: Annals of Oncology (2019)
Efficacy and biomarker analysis of patients (pts) with advanced renal cell carcinoma (aRCC) with sarcomatoid histology (sRCC): Subgroup analysis from the phase III JAVELIN renal 101 trial of first-line avelumab plus axitinib (A + Ax) vs sunitinib (S)
Authors: T.K. Choueiri, J.M.G. Larkin, S.K. Pal, R.J. Motzer, B. Venugopal, B.Y. Alekseev, H. Miyake, G. Gravis, M.A. Bilen, A. Chudnovsky, K.A. Ching, M. Mariani, P.B. Robbins, B. Huang, A. di Pietro, L. Albiges
Journal: Annals of Oncology (2019)
N-terminal B-type natriuretic peptide (NT-proBNP) as an independed prognostic marker for patients with newly diagnosed multiple myeloma complicated by dialysis-dependent renal failure
Authors: S.V. Semochkin, E.I. Zhelnova, E.N. Misyurina, A.V. Cherkasova, D.E. Gagloeva, O.N. Kotenko, A.I. Ushakova, N.A. Arefeva, T.N. Tolstykh, E.A. Baryakh, K.V. Yatskov, D.O. Sinyavkin, I.V. Samsonova, M.A. Lysenko
Journal: Annals of Oncology (2019)
Including Relative Adrenal Insufficiency in Definition and Classification of Acute-on-Chronic Liver Failure
Authors: Salvatore Piano, Elisa Favaretto, Marta Tonon, Giorgia Antonelli, Alessandra Brocca, Antonietta Sticca, Sara Mareso, Enrico Gringeri, Carla Scaroni, Mario Plebani, Francesco Paolo Russo, Patrizia Burra, Umberto Cillo, Paolo Angeli
Journal: Clinical Gastroenterology and Hepatology (2019)
CRISPR-Cas9 Screens Identify the RNA Helicase DDX3X as a Repressor of C9ORF72 (GGGGCC)n Repeat-Associated Non-AUG Translation
Authors: Weiwei Cheng, Shaopeng Wang, Zhe Zhang, David W. Morgens, Lindsey R. Hayes, Soojin Lee, Bede Portz, Yongzhi Xie, Baotram V. Nguyen, Michael S. Haney, Shirui Yan, Daoyuan Dong, Alyssa N. Coyne, Junhua Yang, Fengfan Xian, Don W. Cleveland, Zhaozhu Qiu, Jeffrey D. Rothstein, James Shorter, Fen-Biao Gao, Michael C. Bassik, Shuying Sun
Journal: Neuron (2019)
Risk factors for developing acute gastrointestinal, skin or respiratory infections following obstacle and mud run participation, the Netherlands, 2017
Authors: Elisabeth M den Boogert, Danielle M Oorsprong, Ewout B Fanoy, Alexander CAP Leenders, Alma Tostmann, Adriana SG van Dam
Journal: Eurosurveillance (2019)

Background In the Netherlands, obstacle, mud and survival runs are increasingly popular. Although outbreaks of gastroenteritis have been reported following these events, associated health risks have not been systematically assessed. Aim To investigate the incidence of acute gastrointestinal infections (AGI), skin infections (SI) and respiratory infections (RI) among obstacle run participants, as well as risk factors. Methods Between April and October 2017, we conducted a retrospective cohort study among 2,900 participants of 17 obstacle runs in the Netherlands. Demographic, symptomatic and behavioural data were collected from participants via an online questionnaire 1 week after participation in an obstacle run. Stool specimens were obtained from respondents for microbiological tests. Adjusted relative risks (aRR) and 95% confidence intervals (CI) using multilevel binomial regression analysis were calculated. Results Of 2,646 respondents (median age: 33 years; 53% male), 76 had AGI after the obstacle run; ingesting mud was associated with AGI (aRR: 1.7; 95% CI: 1.2–4.9) and 38 respondents had AGI during or in the week before the obstacle run. Overall, 103 respondents reported SI and 163 RI. Rinsing off in a hot tub was associated with SI (aRR: 2.2; 95% CI: 1.7–2.8). Of 111 stool specimens, 13 tested positive for six different pathogens. No clusters were found. Conclusion The reported incidence of AGI, SI and RI was low. Risk of these infections could be decreased by informing participants on preventive measures, e.g. showering vs rinsing in the hot tub, avoiding ingesting mud and not participating with symptoms of AGI.
Monoclonal Antibody Utilization Characteritics in Patients with Multiple Myeloma
Authors: Sikander Ailawadhi, Abdel-Ghani Azzouqa, Zahara Meghji, Tania Jain, Nancy Diehl, Stephanie P. Gebhardt, Vishal Shah, David O. Hodge, Raj Patel, Prachi Jani, Taimur Sher, Vivek Roy, Meghna Ailawadhi, Victoria R. Alegria, Aneel Paulus, Asher A. Chanan-Khan, Rafael Fonseca
Journal: Blood (2017)
Effects of supervised and adapted exercise program in the quality of life and strength of breast cancer survivors: MAMA MOVE Gaia trial
Authors: A. Joaquim, P. Antunes, C. Garcia, V. Afreixo, A. Amarelo, B. Duarte, M. Vieira, R. Lopes, I. Leão, A. Baptista Capela, L. Helguero, A. Alves
Journal: Annals of Oncology (2019)
Survival prolongation by rationale innovative genomics (SPRING): An international WIN consortium phase I study exploring safety and efficacy of avelumab, palbociclib, and axitinib in advanced non-small cell lung cancer (NSCLC) with integrated genomic and transcriptomic correlates
Authors: B. Solomon, A. Callejo, J. Bar, G. Berchem, L. Bazhenova, P. Saintigny, E. Raymond, N. Girard, R. Sulaiman, C. Bresson, F. Wunder, J.J. Lee, J. Raynaud, E. Rubin, B. Young, V. Lazar, E. Felip, A. Onn, B. Leyland-Jones, R. Kurzrock
Journal: Annals of Oncology (2019)
Extracorporeal Chloride Removal by Electrodialysis. A Novel Approach to Correct Acidemia
Authors: Alberto Zanella, Pietro Caironi, Luigi Castagna, Emanuele Rezoagli, Domenico Salerno, Eleonora Scotti, Vittorio Scaravilli, Salua A. Deab, Thomas Langer, Tommaso Mauri, Michele Ferrari, Daniele Dondossola, Manuela Chiodi, Francesco Zadek, Federico Magni, Stefano Gatti, Luciano Gattinoni, Antonio M. Pesenti
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale: Acidemia is a severe condition among critically ill patients. Despite lack of evidence, sodium bicarbonate is frequently used to correct pH; however, its administration is burdened by several side effects. We hypothesized that the reduction of plasma chloride concentration could be an alternative strategy to correct acidemia.Objectives: To evaluate feasibility, safety, and effectiveness of a novel strategy to correct acidemia through extracorporeal chloride removal by electrodialysis.Methods: Ten swine (six treated and four control animals) were sedated, mechanically ventilated and connected to an extracorporeal electrodialysis device capable of selectively removing chloride. In random order, an arterial pH of 7.15 was induced either through reduction of ventilation (respiratory acidosis) or through lactic acid infusion (metabolic acidosis). Acidosis was subsequently sustained for 12–14 hours. In treatment pigs, soon after reaching target acidemia, electrodialysis was started to restore pH.Measurements and Main Results: During respiratory acidosis, electrodialysis reduced plasma chloride concentration by 26 ± 5 mEq/L within 6 hours (final pH = 7.36 ± 0.04). Control animals exhibited incomplete and slower compensatory response to respiratory acidosis (final pH = 7.29 ± 0.03; P < 0.001). During metabolic acidosis, electrodialysis reduced plasma chloride concentration by 15 ± 3 mEq/L within 4 hours (final pH = 7.34 ± 0.07). No effective compensatory response occurred in control animals (final pH = 7.11 ± 0.08; P < 0.001). No complications occurred.Conclusions: We described the first in vivo application of an extracorporeal system targeted to correct severe acidemia by lowering plasma chloride concentration. Extracorporeal chloride removal by electrodialysis proved to be feasible, safe, and effective. Further studies are warranted to assess its performance in the presence of impaired respiratory and renal functions.
Effect of Intensive Versus Standard Lipid-Lowering Treatment With Atorvastatin on the Progression of Calcified Coronary Atherosclerosis Over 12 Months
Authors: AxelSchmermund, StephanAchenbach, ThomasBudde, YuriBuziashvili, AndreasFörster, GuyFriedrich, MichaelHenein, GertKerkhoff, FriedrichKnollmann, ValeryKukharchuk, AvijitLahiri, RomanLeischik, WernerMoshage, MichaelSchartl, WinfriedSiffert, ElisabethSteinhagen-Thiessen, ValentinSinitsyn, AnjaVogt, BurkhardWiedeking, RaimundErbel
Journal: Circulation (2006)

Background— Recent clinical trials have suggested that intensive versus standard lipid-lowering therapy provides for additional benefit. Electron-beam computed tomography provides the opportunity to quantify the progression of coronary artery calcification (CAC) in serial measurements. Methods and Results— In a multicenter, randomized, double-blind trial, 471 patients (age 61±8 years) who had no history of coronary artery disease and no evidence of high-grade coronary stenoses (>50% diameter reduction) were randomized if they had ≥2 cardiovascular risk factors and moderate calcified coronary atherosclerosis as evidenced by a CAC score ≥30. Patients were assigned to receive 80 mg or 10 mg of atorvastatin per day over 12 months. Progression of CAC volume scores could be analyzed in 366 patients. After pretreatment with 10 mg of atorvastatin for 4 weeks, 12 months of study medication reduced LDL cholesterol from 106±22 to 87±33 mg/dL in the group randomized to receive 80 mg of atorvastatin (P<0.001), whereas...
Validation of an Oral Disease Severity Score (ODSS) tool for use in oral mucous membrane pemphigoid
Authors: M. Ormond, H. McParland, P. Thakrar, A.N.A. Donaldson, M. Andiappan, R.J. Cook, M.E. Escudier, J. Higham, E. Hullah, R. McMillan, J. Taylor, P.J. Shirlaw, S.J. Challacombe, J.F. Setterfield
Journal: British Journal of Dermatology (2019)

Mucous membrane pemphigoid (MMP) is a rare autoimmune bullous disease predominantly affecting the oral mucosa. Optimal management relies upon thorough clinical assessment and documentation at each visit. The primary aim of this study was to validate the Oral Disease Severity Score (ODSS) for the assessment of oral involvement in MMP. We also compared its inter‐ and intraobserver reliability with those of the oral parts of the Mucous Membrane Pemphigoid Disease Area Index (MMPDAI), Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and Physician's Global Assessment (PGA). Fifteen patients with mild‐to‐moderately severe oral MMP were scored for disease severity by 10 oral medicine clinicians from four U.K. centres using the ODSS, the oral sections of MMPDAI and ABSIS, and PGA. Two clinicians rescored all patients after 2 h. In terms of reliability, the interobserver ODSS total score intraclass correlation coefficient (ICC) was 0·97, MMPDAI activity 0·59 and damage 0·15, ABSIS total 0·84, and PGA 0·72. The intraobserver ICCs (two observers) for ODSS total were 0·97 and 0·93; for MMPDAI activity 0·93 and 0·70 and damage 0·93 and 0·79; for ABSIS total 0·99 and 0·94; and for PGA 0·92 and 0·94. Convergent validity between ODSS and MMPDAI was good (correlation coefficient 0·88). The mean ± SD time for completion of ODSS was 93 ± 31 s, with MMPDAI 102 ± 24 s and ABSIS involvement 71 ± 18 s. The PGA took < 5 s. This study has validated the ODSS for the assessment of oral MMP. It has shown superior interobserver agreement over MMPDAI, ABSIS and PGA, and superior intraobserver reliability to MMPDAI. It is quick and easy to perform. What's already known about this topic? There are no validated scoring methodologies for oral mucous membrane pemphigoid (MMP). Proposed disease activity scoring tools for MMP include the Mucous Membrane Disease Area Index (MMPDAI) and the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS). The Oral Disease Severity Score (ODSS) has been validated for use in oral pemphigus vulgaris (PV). It has been shown to be reliable and sensitive in both lichen planus (LP) and MMP. What does this study add? The ODSS has been shown to be a thorough, sensitive and reproducible, yet quick scoring tool for the assessment of oral involvement in MMP. Its versatility for use in oral PV, MMP and LP is an added advantage over other scoring methodologies. What are the clinical implications of this work? We propose that the ODSS be used as a clinical scoring tool for monitoring activity in oral MMP in clinical practice as well as for use in multicentre studies.
Capita: BMA poised to launch legal challenge to NHS England over archiving error
Authors: Gareth Iacobucci
Journal: BMJ (2019)

The BMA is seeking general practices to join a potential legal challenge against NHS England over a blunder that saw 150 000 patient records wrongly archived by the private company Capita.

In May NHS England wrote to practices to inform them that the records were mistakenly archived rather than transferred to surgeries, after an error by the Primary Care Support England programme, which is delivered by Capita.1

The records were later sent back to practices, which were told by NHS England to undertake an assessment of harm for each patient affected.

The BMA’s …
Immunogenicity of BRCA1-deficient ovarian cancers is driven through DNA sensing and is augmented by PARP inhibition
Authors: M. Bruand, D. Barras, M. Mina, E. Lanitis, C. Chong, J. Dorier, J. Walton, M. Bassani-Sternberg, L. Kandalaft, I.A. McNeish, E. Swisher, M. Delorenzi, B. Ren, G. Ciriello, M. Irving, S. Rusakiewicz, P. Foukas, F. Martinon, D. Dangaj, G. Coukos
Journal: Annals of Oncology (2019)
Genome-wide discovery and validation of diagnostic DNA methylation-based biomarkers for hepatocellular cancer detection in circulating cell free DNA
Authors: Ryan A. Hlady, Xia Zhao, Xiaoyu Pan, Ju Dong Yang, Fowsiyo Ahmed, Samuel O. Antwi, Nasra H. Giama, Tushar Patel, Lewis R. Roberts, Chen Liu, Keith D. Robertson
Journal: Theranostics (2019)

Hepatocellular carcinoma (HCC), the most prevalent form of liver cancer, is growing in incidence but treatment options remain limited, particularly for late stage disease. As liver cirrhosis is the principal risk state for HCC development, markers to detect early HCC within this patient population are urgently needed. Perturbation of epigenetic marks, such as DNA methylation (5mC), is a hallmark of human cancers, including HCC. Identification of regions with consistently altered 5mC levels in circulating cell free DNA (cfDNA) during progression from cirrhosis to HCC could therefore serve as markers for development of minimally-invasive screens of early HCC diagnosis and surveillance. Methods: To discover DNA methylation derived biomarkers of HCC in the background of liver cirrhosis, we profiled genome-wide 5mC landscapes in patient cfDNA using the Infinium HumanMethylation450k BeadChip Array. We further linked these findings to primary tissue data available from TCGA and other public sources. Using biological and statistical frameworks, we selected CpGs that robustly differentiated cirrhosis from HCC in primary tissue and cfDNA followed by validation in an additional independent cohort. Results: We identified CpGs that segregate patients with cirrhosis, from patients with HCC within a cirrhotic liver background, through genome-wide analysis of cfDNA 5mC landscapes. Lasso regression analysis pinpointed a panel of probes in our discovery cohort that were validated in two independent datasets. A panel of five CpGs (cg04645914, cg06215569, cg23663760, cg13781744, and cg07610777) yielded area under the receiver operating characteristic (AUROC) curves of 0.9525, 0.9714, and 0.9528 in cfDNA discovery and tissue validation cohorts 1 and 2, respectively. Validation of a 5-marker panel created from combining hypermethylated and hypomethylated CpGs in an independent cfDNA set by bisulfite pyrosequencing yielded an AUROC of 0.956, compared to the discovery AUROC of 0.996. Conclusion: Our finding that 5mC markers derived from primary tissue did not perform well in cfDNA, compared to those identified directly from cfDNA, reveals potential advantages of starting with cfDNA to discover high performing markers for liquid biopsy development.
A phase I study of Sym021, an anti-PD-1 antibody (Ab), alone and in combination with Sym022 (anti-LAG-3) or Sym023 (anti-TIM-3)
Authors: A. Spreafico, F. Janku, J.A. Rodon, A.W. Tolcher, S.R. Chandana, M. Oliva, S. Musalli, L. Knauss, M. Kragh, L. Alifrangis, C. Fröhlich, M.C. Melander, T. Blondal, M.W. Pedersen, J. Lantto, D. Wood, P.I. Nadler, I.D. Horak, L.L. Siu, N. Lakhani
Journal: Annals of Oncology (2019)
Chronic Kidney Disease Diagnosis and Management
Authors: Teresa K. Chen, Daphne H. Knicely, Morgan E. Grams
Journal: JAMA (2019)

<h3>Importance</h3> Chronic kidney disease (CKD) is the 16th leading cause of years of life lost worldwide. Appropriate screening, diagnosis, and management by primary care clinicians are necessary to prevent adverse CKD-associated outcomes, including cardiovascular disease, end-stage kidney disease, and death. <h3>Observations</h3> Defined as a persistent abnormality in kidney structure or function (eg, glomerular filtration rate [GFR] &lt;60 mL/min/1.73 m<sup>2</sup>or albuminuria ≥30 mg per 24 hours) for more than 3 months, CKD affects 8% to 16% of the population worldwide. In developed countries, CKD is most commonly attributed to diabetes and hypertension. However, less than 5% of patients with early CKD report awareness of their disease. Among individuals diagnosed as having CKD, staging and new risk assessment tools that incorporate GFR and albuminuria can help guide treatment, monitoring, and referral strategies. Optimal management of CKD includes cardiovascular risk reduction (eg, statins and blood pressure management), treatment of albuminuria (eg, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers), avoidance of potential nephrotoxins (eg, nonsteroidal anti-inflammatory drugs), and adjustments to drug dosing (eg, many antibiotics and oral hypoglycemic agents). Patients also require monitoring for complications of CKD, such as hyperkalemia, metabolic acidosis, hyperphosphatemia, vitamin D deficiency, secondary hyperparathyroidism, and anemia. Those at high risk of CKD progression (eg, estimated GFR &lt;30 mL/min/1.73 m<sup>2</sup>, albuminuria ≥300 mg per 24 hours, or rapid decline in estimated GFR) should be promptly referred to a nephrologist. <h3>Conclusions and Relevance</h3> Diagnosis, staging, and appropriate referral of CKD by primary care clinicians are important in reducing the burden of CKD worldwide.
Ex vivo culture of adult CD34+ stem cells using functional highly porous polymer scaffolds to establish biomimicry of the bone marrow niche
Authors: C.E. Severn, A.M. Eissa, C.R. Langford, A. Parker, M. Walker, J.G.G. Dobbe, G.J. Streekstra, N.R. Cameron, A.M. Toye
Journal: Biomaterials (2019)

Haematopoiesis, the process of blood production, occurs from a tiny contingent of haematopoietic stem cells (HSC) in highly specialised three-dimensional niches located within the bone marrow. When haematopoiesis is replicated using in vitro two-dimensional culture, HSCs rapidly differentiate, limiting self-renewal. Emulsion-templated highly porous polyHIPE foam scaffolds were chosen to mimic the honeycomb architecture of human bone. The unmodified polyHIPE material supports haematopoietic stem and progenitor cell (HSPC) culture, with successful culture of erythroid progenitors and neutrophils within the scaffolds. Using erythroid culture methodology, the CD34+ population was maintained for 28 days with continual release of erythroid progenitors. These cells are shown to spontaneously repopulate the scaffolds, and the accumulated egress can be expanded and grown at large scale to reticulocytes. We next show that the polyHIPE scaffolds can be successfully functionalised using activated BM(PEG)2 (1,8-bismaleimido-diethyleneglycol) and then a Jagged-1 peptide attached in an attempt to facilitate notch signalling. Although Jagged-1 peptide had no detectable effect, the BM(PEG)2 alone significantly increased cell egress when compared to controls, without depleting the scaffold population. This work highlights polyHIPE as a novel functionalisable material for mimicking the bone marrow, and also that PEG can influence HSPC behaviour within scaffolds.
Early response evaluation and CEA response in patients treated in a Danish randomized study comparing trifluridine/tipiracil (TAS-102) with or without bevazicumab in patients with chemorefractory metastatic colorectal cancer (mCRC)
Authors: C. Qvortrup, M. Yilmaz, S. Möller, D. Zitnjak, L. Maltha, M. Krogh, L Noergaard Petersen, F. Hejlesen, S.B. Winther, K.G. Thomsen, P. Pfeiffer
Journal: Annals of Oncology (2019)
Osimertinib in epidermal growth factor receptor (EGFR) T790M advanced non-small cell lung cancer (NSCLC): Analysis of patients with central nervous system (CNS) metastases in a real-world study (ASTRIS)
Authors: G. Metro, M. Provencio, D.-W. Kim, B.C. Cho, K. Park, Y. Pan, Y. Shi, R. Migliorino, M. Tiseo, J. Yu, Q. Zhou, A. Santo, A. Ardizzoni, Y. Hu, Y.-L. Wu, S.-W. Kim, M. Miranda, A. Fernandes, F. de Marinis
Journal: Annals of Oncology (2019)
Prognostic factors influencing outcome after therapy with brentuximab vedotin in patients with relapsed or refractory Hodgkin’s lymphoma
Authors: V.S. Goranova-Marinova, K. Ignatova, P. Ganeva, E. Spasov, G. Arnaudov, I. Micheva, L. Gercheva, A. Radinov, R. Petrova, G. Tzvetkova, E. Hadzhiev, L. Bogdanov, N. Tzvetkov, B. Spasov, Z. Grudeva-Popova, D. Tumbeva
Journal: Annals of Oncology (2019)