tbuckley/cabot-search huggingface dataset:
Sex-Based Disparities in the Hourly Earnings of Surgeons in the Fee-for-Service System in Ontario, Canada
Authors: Fahima Dossa, Andrea N. Simpson, Rinku Sutradhar, David R. Urbach, George Tomlinson, Allan S. Detsky, Nancy N. Baxter
Journal: JAMA Surgery (2019)

<h3>Importance</h3> Sex-based income disparities are well documented in medicine and most pronounced in surgery. These disparities are commonly attributed to differences in hours worked. One proposed solution to close the earnings gap is a fee-for-service payment system, which is theoretically free of bias. However, it is unclear whether a sex-based earnings gap persists in a fee-for-service system when earnings are measured on the basis of hours worked. <h3>Objective</h3> To determine whether male and female surgeons have similar earnings for each hour spent operating in a fee-for-service system. <h3>Design, Setting, and Participants</h3> This cross-sectional, population-based study used administrative databases from a fee-for-service, single-payer health system in Ontario, Canada. Surgeons who submitted claims for surgical procedures performed between January 1, 2014, and December 31, 2016, were included. Data analysis took place from February 2018 to December 2018. <h3>Exposures</h3> Surgeon sex. <h3>Main Outcomes and Measures</h3> This study compared earnings per hour spent operating between male and female surgeons and earnings stratified by surgical specialty in a matched analysis. We explored factors potentially associated with earnings disparities, including differences in procedure duration and type between male and female surgeons and hourly earnings for procedures performed primarily on male vs female patients. <h3>Results</h3> We identified 1 508 471 surgical procedures claimed by 3275 surgeons. Female surgeons had practiced fewer years than male surgeons (median [interquartile range], 8.4 [2.9-16.6] vs 14.7 [5.9-25.7] years;<i>P</i> &lt; .001), and the largest proportion of female surgeons practiced gynecology (400 of 819 female surgeons [48.8%]). Hourly earnings for female surgeons were 24% lower than for male surgeons (relative rate, 0.76 [95% CI, 0.74-0.79];<i>P</i> &lt; .001). This disparity persisted after adjusting for specialty and in matched analysis stratified by specialty, with the largest mean differences in cardiothoracic surgery (in US dollars: $59.64/hour) and orthopedic surgery ($55.45/hour). There were no differences in time taken by male and female surgeons to perform common procedures; however, female surgeons more commonly performed procedures with the lowest hourly earnings. <h3>Conclusions and Relevance</h3> Even within a fee-for-service system, male and female surgeons do not have equal earnings for equal hours spent working, suggesting that the opportunity to perform the most lucrative surgical procedures is greater for men than women. These findings call for a comprehensive analysis of drivers of sex-based earning disparities, including referral patterns, and highlight the need for systems-level solutions.
Amplification of the Prolactin Receptor Gene in Mammary Lobular Neoplasia.
Authors: D. Tran-Thanh, D. Tran-Thanh, N. Arneson, M. Pintilie, K. Warren, A. Bane, F. O'Malley, F. O'Malley, S. Done, S. Done
Journal: Cancer Research (2009)

Abstract Background: Lobular carcinoma in situ (LCIS) has long been considered a marker of increased risk of cancer in both breasts. However, recent studies have shown that it can behave as a non-obligate precursor lesion as well. The biology and natural history of LCIS still remains ill defined in part because it is a challenging lesion to study as it usually does not have an identifiable gross appearance and is only recognized in fixed tissue specimens.Material and Methods: Using array comparative genomic hybridization (aCGH) we have analyzed regions of amplification found in LCIS and adjacent invasive lobular carcinoma (ILC) in a series of thirteen cases of archival patient samples from our institution. Degenerate oligonucleotide primed (DOP) PCR was performed for whole genome amplification of the extracted DNA from microdissected tissue samples prior to microarray analysis. Analysis of microarray data was performed using Significance Analysis of Microarrays (SAM). Of the ten most amplified genes in LCIS (highest SAM scores), one was selected for quantitative real time PCR (Q-PCR) validation due to the limited amount of material available from these cases. Q-PCR validation was performed on samples from 8 cases of LCIS and invasive lobular carcinoma and 12 archival cases of ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) for comparison.Results: Amongst the 10 genes with the highest SAM scores, the prolactin receptor gene (PRLR) was selected for further Q-PCR validation in our limited samples. Amplification of PRLR was confirmed by Q-PCR in 4/8 (50%) of cases of LCIS and 4/8 (50%) cases of ILC, compared to 0/12 (0%) cases of DCIS and 3/12 (25%) cases of IDC. When LCIS and ILC were combined into one group, there was more amplification of the prolactin receptor gene when compared to the DCIS and IDC group (p= 0.01). The level of amplification between the two groups also differed in the range of copy number values, which was lower in the ductal group (0.78-1.58, n=24) compared to the lobular group (0.92-3.68, n=16) (p&amp;lt;0.05).Conclusion: We have identified the prolactin receptor as a potential molecular target in lobular neoplasia using array comparative genomic hybridization. In contrast, we have shown that the prolactin receptor may not be as important for the progression of ductal lesions. These results support the view that lobular and ductal carcinoma evolve along separate pathways. Validation of the expression of PRLR in a larger number of LCIS cases is warranted. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4151.
Impact of Abiraterone Acetate plus Prednisone or Enzalutamide on Patient-reported Outcomes in Patients with Metastatic Castration-resistant Prostate Cancer: Final 12-mo Analysis from the Observational AQUARiUS Study
Authors: Antoine Thiery-Vuillemin, Mads Hvid Poulsen, Edouard Lagneau, Guillaume Ploussard, Alison Birtle, Louis-Marie Dourthe, Dominique Beal-Ardisson, Elias Pintus, Redas Trepiakas, Florence Lefresne, Martin Lukac, Suzy Van Sanden, Genevieve Pissart, Alison Reid
Journal: European Urology (2019)

Few studies have examined patient-reported outcomes (PROs) with abiraterone acetate plus prednisone (abiraterone) versus enzalutamide in metastatic castration-resistant prostate cancer (mCRPC). To determine the impact of abiraterone and enzalutamide on PROs. AQUARiUS (NCT02813408) was a prospective, 12-mo, observational study in patients with mCRPC from Denmark, France, and the UK. Abiraterone or enzalutamide treatment according to routine practise. PROs were collected over 12 mo using Functional Assessment of Cancer Therapy—Cognitive Function (FACT-Cog), Brief Fatigue Inventory—Short Form (BFI-SF), Brief Pain Inventory—Short Form, and European Organisation for Research and Treatment of Cancer—Quality of Life Questionnaire (QLQ-C30) at baseline and routine visits. Outcomes included mean change in PROs, patients with clinically meaningful worsening (CMW) in PROs, and safety. Data were analysed using repeated measures linear and logistic models adjusted for baseline characteristics. Abiraterone-treated (N = 105) and enzalutamide-treated (N = 106) patients were included. Key PRO items (cognitive impairments and fatigue) were significantly (p < 0.05) in favour of abiraterone versus enzalutamide during the study. "Perceived cognitive impairment" and "comments from others" (FACT-Cog); "fatigue right now", "usual level of fatigue", and "worst level of fatigue" (BFI-SF); and "cognitive functioning" and "fatigue" (QLQ-C30) were significantly in favour of abiraterone over enzalutamide for three or more consecutive periods up to month 12. From study initiation, significantly fewer patients receiving abiraterone experienced one or more CMW episode in cognition and fatigue. Fatigue and asthenia (adverse events) were lower with abiraterone than with enzalutamide (5% vs 15% and 10% vs 11%, respectively). There were no treatment-related deaths. Limitations included lack of randomisation. In a real-world setting, this 12-mo analysis suggests an advantage of abiraterone acetate plus prednisone over enzalutamide on fatigue and cognitive function; this finding occurred early after treatment initiation. This difference should be considered when choosing treatment. This study looked at the effect of two treatments (abiraterone acetate plus prednisone and enzalutamide) for metastatic castration-resistant prostate cancer on patient quality of life over 12 mo. Using established questionnaires, patients reported that they experienced less fatigue and cognitive impairments (including memory loss and reduced thinking abilities) with abiraterone acetate plus prednisone than with enzalutamide.
MK5 Regulates YAP Stability and Is a Molecular Target in YAP-Driven Cancers
Authors: Jimyung Seo, Min Hwan Kim, Hyowon Hong, Hyunsoo Cho, Seongyeol Park, Sang Kyum Kim, Joon Kim
Journal: Cancer Research (2019)

Abstract Transcriptional regulator YAP is activated in multiple human cancers and plays critical roles in tumor initiation, progression, metastasis, and drug resistance. However, therapeutic targeting of the Hippo–YAP pathway has been challenging due to its low druggability and limited knowledge of YAP regulation in cancer. Here we present a functional screen and identify a novel therapeutic target for YAP-driven tumorigenesis. RNAi screening using an oncogenic YAP activation model identified the serine/threonine kinase MK5 as a positive regulator of YAP. MK5 physically interacted with YAP and counteracted CK1δ/ϵ-mediated YAP ubiquitination and degradation independent of LATS1/2. MK5 kinase activity was essential for protecting YAP from ubiquitin-mediated degradation and cytoplasmic retention. Downregulating MK5 expression inhibited the survival of YAP-activated cancer cell lines and mouse xenograft models. MK5 upregulation was associated with high levels of YAP expression and poor prognosis in clinical tumor samples, confirming its important role for YAP activity in human cancer. These results uncover MK5 as a novel factor that regulates YAP stability, and targeting the YAP degradation pathway controlled by MK5 is a potential strategy for suppressing YAP activity in cancer. Significance: These findings reveal MK5 is a novel kinase that regulates YAP in a LATS-independent manner and can be targeted for cancer therapy.
Fluoropyrimidine-induced cardiotoxicity in colorectal cancer patients: Preliminary data from the prospective observational CHECKPOINT trial (NCT02665312)
Authors: P. Lombardi, G. Aimar, I. Depetris, A. Bonzano, R. Filippi, E. Fenocchio, V. Quarà, M. Milanesio, R. Ferraris, C. Cagnazzo, C Peraldo Neia, M. Basiricò, G. Cavalloni, M. Aglietta, F. Leone
Journal: Annals of Oncology (2019)
Correlation of clinical and pathological features with the tumour microenvironment in DCIS: An institutional experience
Authors: A. Eapen, Y. Lyou, L. Eisenbud, R. Mehta, K. Lane, T.T. Lama, P. Daroui, E. Lin, A. Ziogas, R. Parajuli
Journal: Annals of Oncology (2019)
Abstract 19024: Differences in Mitral Valve Marginal Chordae Tendineae Length in Patients with Functional and Degenerative Mitral Regurgitation Using 3D Transesophageal Echocardiography from the Transgastric Approach
Authors: Kikuko Obase, Lynn Weinert, Kimberly Kesner, Aaron Barry, Karima Addetia, Joseph D Roberts, Mohammed M Minhaj, Victor Mor-Avi, Valluvan Jeevanandam, Roberto M Lang
Journal: Circulation (2014)

Background: Patients with degenerative mitral valve disease (MVD) frequently have elongated chordae tendineae. In patients with functional mitral regurgitation (FMR), leaflet adaptation has been de...
Predictive model for survival in advanced non-small cell lung cancer (NSCLC) treated with frontline pembrolizumab
Authors: X Mielgo Rubio, M E Olmedo Garcia, M Sereno Moyano, C. Aguado, J.A. Núñez, M Domine Gomez, A M Sánchez Peña, I Nalda Ariza, S Cerezo Gonzalez, R Alvarez Cabellos, L Cabezón Gutiérrez, C Pangua Mendez, R. Cervera, A Calles Blanco, R López Castro, J M Sanchez Torres, A Lopez Martin, A Velastegui Ordonez, E Pérez Fernández, P. Cruz
Journal: Annals of Oncology (2019)
A phase 1 study of filanesib, carfilzomib, and dexamethasone in patients with relapsed and/or refractory multiple myeloma
Authors: Hans C. Lee, Jatin J. Shah, Lei Feng, Elisabet E. Manasanch, Rebecca Lu, Ashley Morphey, Brandon Crumpton, Krina K. Patel, Michael L. Wang, Raymond Alexanian, Sheeba K. Thomas, Donna M. Weber, Robert Z. Orlowski
Journal: Blood Cancer Journal (2019)
ATALANTE-1 randomized phase III trial, OSE-2101 versus standard treatment as second or third-line in HLA-A2 positive advanced non-small cell lung cancer (NSCLC) patients
Authors: E. Felip, B. Besse, R. Dziadziuszko, M. Cobo Dols, F. Denis, M.-R. García-Campelo, D. Debieuvre, A. Catino, M.T. Moran Bueno, A.-C. Madroszyk Flandin, P. Masson, C. Chouaid, P. Lianes, F. Cappuzzo, A. Delmonte, G. Robinet, G. Romano, V. Gabarre, J. Remon Masip, G. Giaccone
Journal: Annals of Oncology (2019)
Reduced Incidence of Hepatic Encephalopathy and Higher Odds of Resolution Associated With Eradication of HCV Infection
Authors: Elliot B. Tapper, Neehar D. Parikh, Pamela K. Green, Kristin Berry, Akbar K. Waljee, Andrew M. Moon, George N. Ioannou
Journal: Clinical Gastroenterology and Hepatology (2019)
Human Umbilical Cord Derived Mesenchymal Stromal Cells to Treat Steroid-Refractory Acute GvHD III/IV or Overlap Syndrome: Interim Analysis of a Multicenter Phase I/II Study
Authors: Maria Mico', Alessandra Algarotti, Anna Grassi, Chiara Pavoni, Francesco Onida, Nicola Mordini, Maria Luisa Ferrari, Federico Lussana, Maria Chiara Finazzi, Daniela Taurino, Chiara Capelli, Martino Introna, Alessandro Rambaldi
Journal: Blood (2018)
Proton pump inhibitors interact with transport of both imatinib and nilotinib.
Authors: Deborah White, Verity Saunders, Steven Quinn, Paul Manley, Timothy Hughes
Journal: Cancer Research (2007)

1635  Imatinib (IM) is the current standard of care for chronic myeloid leukaemia (CML). Recent studies have shown that IM interacts with the efflux transporters ABCB1 and ABCG2. Furthermore, proton pump inhibitors (PPI) such as pantoprazole and esomeprazole (Eso), commonly used for symptomatic relief in patients on IM, also interact with these efflux transporters and improve IM CNS penetration in mice. Nilotinib (NIL) is a second generation tyrosine kinase inhibitor which is 20-fold more potent than IM in vitro. The drug transporters responsible for intracellular transport of NIL are currently less well defined than those for IM. We examined the effect of concomitant administration of PPI with IM and NIL using 14C labeled drugs, in an assay to measure intracellular uptake and retention (IUR) of the drug in primary CML cells.  Table 1: Median % change in IUR from untreated in the presence of PPI  These results demonstrate a decrease in the IUR for IM in the presence of both PPI, and in contrast an increase in the IUR for nilotinib, suggesting the mode of interaction may be different for both drugs. Given the noted interaction with PPI and efflux, the increased IUR for NIL suggests NIL is transported by ABCB1 and/or ABCG2. Preliminary experiments assessing the effect of temperature (4oC vs 37oC) on the IUR of VBL100 cells (ABCB1 expressing line) further suggest that NIL is transported by ABCB1. The decreased IUR for imatinib is unexpected, and not previously described. This suggests that PPI may interact with either active (OCT-1) or passive transport mechanisms for imatinib. In summary, we show significant, but distinct interactions between PPI and both IM and NIL. Both responses may result in clinically significant changes with concomitant administration, and therefore warrant further investigation.
Practice‐based differences in paediatric DLE
Authors: L. Arkin, K. Buhr, H. Brandling‐Bennett, Y. Chiu, B. Chong, M. Curran, R. Hunt, A.S. Paller, V. Werth, M. Klein‐Gitelman, E. Scheven, K. Ardalan
Journal: British Journal of Dermatology (2019)

The term ‘lupus’ refers to a range of related disorders. Discoid lupus erythematosus (DLE) is a form of lupus in the skin, which is rare in children. It can lead to disfiguring scarring. Some patients develop systemic lupus (SLE), a type of lupus that affects the whole body, which can lead to damage to multiple organs. Small studies have suggested that 25 to 30% of children with DLE develop SLE over time, but risk factors for this are not known. Early diagnosis and treatment of SLE are helpful. This study used a survey approach to compare practice patterns between two medical specialties, academic rheumatologists and dermatologists, in the United States and Canada, caring for children with DLE. The study aimed to identify areas of agreement but also practice-based differences between groups. Consensus (agreement) occurred when 70% or more of both specialties agreed. The authors found consensus that certain laboratory studies should be checked for all children at diagnosis of DLE. Both groups agreed that the presence of “other auto-antibodies besides ANA”, arthritis, or nephritis were high-risk features for SLE that should increase screening for systemic disease. There were no other agreed-upon risk factors for SLE, including those that have previously been shown in adults with DLE. Both groups agreed that first-line systemic therapy (whole body treatment) for widespread DLE should be hydroxychloroquine. The authors could not agree on which medications to use for resistant skin disease. Overall, the study found some areas of agreement but many areas of practice-based difference. More data in children with DLE is necessary to determine best practice approaches. The authors are completing a type of study called a retrospective cohort study that may help to fill these gaps.
Clinical judgments, not algorithms, are key to patient safety—an essay by David Healy and Dee Mangin
Authors: David Healy, Dee Mangin
Journal: BMJ (2019)

When it comes to detecting harms related to drugs, clinicians’ and patients’ judgment trumps trials, say <b>David Healy</b> and <b>Dee Mangin</b>. Failure to realise this is the greatest threat to the safety of medicines
Comparison of filgrastim and pegfilgrastim prophylaxis in sarcoma patients receiving highly myelosuppressive chemotherapy
Authors: P. Tarantino, P. Zagami, P. Trillo, F. Conforti, L. Pala, S. Morganti, E. Ferraro, G. Viale, B.A. Duso, P. D’Amico, A. Marra, D. Trapani, T.M. De Pas
Journal: Annals of Oncology (2019)
Adaptive Radiation of the Flukes of the Family Fasciolidae Inferred from Genome-Wide Comparisons of Key Species
Authors: Young-Jun Choi, Santiago Fontenla, Peter U Fischer, Thanh Hoa Le, Alicia Costábile, David Blair, Paul J Brindley, Jose F Tort, Miguel M Cabada, Makedonka Mitreva
Journal: Molecular Biology and Evolution (2019)

Abstract Liver and intestinal flukes of the family Fasciolidae cause zoonotic food–borne infections that impact both agriculture and human health throughout the world. Their evolutionary history and the genetic basis underlying their phenotypic and ecological diversity are not well understood. To close that knowledge gap, we compared the whole genomes of Fasciola hepatica, Fasciola gigantica, and Fasciolopsis buski and determined that the split between Fasciolopsis and Fasciola took place ∼90 Ma in the late Cretaceous period, and that between 65 and 50 Ma an intermediate host switch and a shift from intestinal to hepatic habitats occurred in the Fasciola lineage. The rapid climatic and ecological changes occurring during this period may have contributed to the adaptive radiation of these flukes. Expansion of cathepsins, fatty-acid-binding proteins, protein disulfide-isomerases, and molecular chaperones in the genus Fasciola highlights the significance of excretory–secretory proteins in these liver-dwelling flukes. Fasciola hepatica and Fasciola gigantica diverged ∼5 Ma near the Miocene–Pliocene boundary that coincides with reduced faunal exchange between Africa and Eurasia. Severe decrease in the effective population size ∼10 ka in Fasciola is consistent with a founder effect associated with its recent global spread through ruminant domestication. G-protein-coupled receptors may have key roles in adaptation of physiology and behavior to new ecological niches. This study has provided novel insights about the genome evolution of these important pathogens, has generated genomic resources to enable development of improved interventions and diagnosis, and has laid a solid foundation for genomic epidemiology to trace drug resistance and to aid surveillance.
Durvalumab plus tremelimumab for the treatment of patients (pts) with refractory and progressive advanced thyroid carcinoma: A phase II multicohort trial (DUTHY / GETNE T1812)
Authors: J. Hernando Cubero, M. Taberna Sanz, A. Carmona Bayonas, L. Iglesias, E. Grande, J.M. Trigo Perez, J.J. Grau, J.M. Lopez-Picazo, B. Castelo, T. Alonso Gordoa, I. Lorenzo, A. Casado Herraez, L. Ugidos, J. Munarriz, J. Lavernia, J. Capdevila
Journal: Annals of Oncology (2019)
Alpelisib (ALP) + fulvestrant (FUL) for patients with hormone receptor–positive (HR+), HER2− advanced breast cancer (ABC): Management and time course of key adverse events of special interest (AESIs) in SOLAR-1
Authors: H.S. Rugo, F. André, T. Yamashita, H. Cerda, I. Toledano, S. Stemmer, J. Cruz Jurado, D. Juric, I. Mayer, E.M. Ciruelos, H. Iwata, P.F. Conte, M. Campone, C. Wilke, D. Mills, I. Lorenzo, M. Miller, S. Loibl
Journal: Annals of Oncology (2019)
Who drops out of cervical cancer screening? Results from the EDIFICE 6 survey
Authors: T. de La Motte Rouge, F. Eisinger, S. Couraud, L. Greillier, C. Touboul, C. Lhomel, M. Rouprêt, J. Viguier, J.-F. Morere
Journal: Annals of Oncology (2019)
Asymptomatic Leishmania infantum infection in blood donors living in an endemic area, northeastern Italy
Authors: Margherita Ortalli, Alessandra Mistral De Pascali, Serena Longo, Nadia Pascarelli, Andrea Porcellini, Deborah Ruggeri, Vanda Randi, Anna Procopio, Maria Carla Re, Stefania Varani
Journal: Journal of Infection (2019)
Pathologic scoring of pre-treatment H&E biopsies predicts overall survival in patients with metastatic clear cell renal cell carcinoma receiving nivolumab monotherapy
Authors: J.E. Stein, S. Signoretti, M. Sznol, Y. Ishii, D.F. McDermott, T.K. Choueiri, J.M. Taube
Journal: Annals of Oncology (2019)
A High Resolution Analysis of Chromosome 21 Amplification In Myeloid Malignancies Reveals An Association with a Specific Cytogenetic Subgroup and Enhanced ERG Gene Expression.
Authors: Hideki Makishima, Hideki Muramatsu, Asahito Hama, Ramon V. Tiu, Yuka Sugimoto, Mikkael A. Sekeres, Yogen Saunthararajah, Michael A McDevitt, Seiji Kojima, Jaroslaw P Maciejewski
Journal: Blood (2010)
Abstract 16750: Effectiveness of Intravenous Phenytoin as Adjuvant Antiarrhythmic Therapy to Suppress Incessant Ventricular Tachydysrhythmias and Ventricular Tachycardia Storm
Authors: Gian Carlo Giove, Michael C Serra, Evelyn Tu, Jay H Curwin, Robert F Coyne, Jonathan S Sussman, Timothy H Mahoney, Stephen L Winters
Journal: Circulation (2013)

Introduced as an antiarrhythmic drug four decades ago, the effectiveness of intravenous phenytoin in the management of incessant ventricular tachydysrhythmias (IVT) and ventricular tachycardia stor...
Impact of nutritional derangement on treatment outcome in advanced non-small-cell lung cancer (A-NSCLC) patients (pts)
Authors: I. Trestini, I. Sperduti, M. Sposito, D. Kadrija, A. Drudi, D. Tregnago, A. Avancini, A. Gkountakos, L. Carbognin, A. Santo, M. D’onofrio, M. Lanza, G. Tortora, E. Bria, M. Milella, S. Pilotto
Journal: Annals of Oncology (2019)
Prevalence and prognostic effect of high tumor mutation burden (TMB-H) across multiple less common solid cancers using a real-world dataset
Authors: D. Backenroth, C. Shao, G. Li, L. Huang, S.K. Pruitt, E. Castellanos, G.M. Frampton, K.R. Carson, T. Snow, G. Singal, D. Fabrizio, B.M. Alexander, F.J. Jin, W. Zhou
Journal: Annals of Oncology (2019)