tbuckley/cabot-search huggingface dataset:
Updated survival outcomes of the phase II study of low starting dose of afatinib as first-line treatment in patients with EGFR mutation-positive non-small cell lung cancer (KTORG1402)
Authors: T. Yokoyama, H. Yoshioka, D. Fujimoto, Y. Demura, K. Hirano, T. Kawai, R. Kagami, T. Ishida, K. Tomii, M. Akai, M. Hirabayashi, T. Nishimura, Y. Nakahara, Y.H. Kim, K. Yoshimura, T. Hirai
Journal: Annals of Oncology (2019)
Lineage of measurable residual disease in patients with chronic myeloid leukemia in treatment-free remission
Authors: Ilaria S. Pagani, Phuong Dang, Verity A. Saunders, Randall Grose, Naranie Shanmuganathan, Chung H. Kok, Lisa Carne, Zandy Rwodzi, Sophie Watts, Jennifer McLean, Jodi Braley, Haley Altamura, David T. Yeung, Susan Branford, Agnes S. M. Yong, Deborah L. White, Timothy P. Hughes, David M. Ross
Journal: Leukemia (2019)
Using in vitro lipolysis and SPECT/CT in vivo imaging to understand oral absorption of fenofibrate from lipid-based drug delivery systems
Authors: Thuy Tran, Peter Bønløkke, Cristina Rodríguez-Rodríguez, Zeynab Nosrati, Pedro Luis Esquinas, Nrupa Borkar, Jakob Plum, Sophie Strindberg, Stoyan Karagiozov, Thomas Rades, Anette Müllertz, Katayoun Saatchi, Urs O. Häfeli
Journal: Journal of Controlled Release (2019)
A Phase 2 Study of the Dual SYK/JAK Inhibitor Cerdulatinib Demonstrates Good Tolerability and Clinical Response in Relapsed/Refractory Peripheral T-Cell Lymphoma and Cutaneous T-Cell Lymphoma
Authors: Steven M. Horwitz, Tatyana A. Feldman, Brian T. Hess, Michael S. Khodadoust, Youn H. Kim, Javier Munoz, Manish R. Patel, Tycel J. Phillips, Stephen D. Smith, Sonali M. Smith, Ryan A. Wilcox, Matt R. Birrell, Janet M. Leeds, Pamela B. Conley, Glenn C. Michelson, Gregory P. Coffey, John T. Curnutte, Paul A. Hamlin
Journal: Blood (2019)
Abstract 15657: Sex as a Biological Variable is Evident Following Deletion of Intestinal Apolipoprotein A1
Authors: Tara Price, John Adams, Johnathan Ballard, Huiping Guo, Andrei Golovko, Ben Morpurgo, Rosemary Walzem
Journal: Circulation (2019)

Apolipoprotein A1 (apoA1) is key to reverse cholesterol transport and HDL functionality. Global apoA1 knockout alters HDL composition and impairs HDL function (JLR, 38:1033). Given that 1/3 of HDL ...
Radiation oncology program directors’ attitudes towards 27 discrete palliative care skills.
Authors: Eric M. Chang, Ann C. Raldow, Anne M. Walling, Percy P. Lee, Emily J Martin
Journal: Journal of Clinical Oncology (2019)

62 Background: Dedicated conferences in palliative care have been proposed as an ACGME requirement for radiation oncology (RO) residency programs. We assessed RO program directors’ attitudes towards discrete palliative care skills. Methods: In April 2019, we surveyed 93 United States RO residency program directors. The survey assessed program directors’ views of 27 discrete palliative care skills in eight domains adapted from the American Society of Clinical Oncology/American Academy of Hospice and Palliative Medicine guidance statement defining high-quality palliative care in oncology. Using a nine-point scale, respondents rated each skill on three constructs: 1) importance to high-quality cancer care, 2) scope within RO practice, and 3) importance in RO residency education. Skills were categorized as “Included” (median score ≥7 for all constructs), “Excluded” (median score ≤3 for all constructs), or “Uncertain” (all other skills) using a composite score of all constructs. Results: Twenty-nine program directors (response rate 31%) completed the survey. Of the 27 skills, respondents rated 100% of the skills as important to care (median score ≥7), 70% of the skills as within the scope of RO practice, and 81% of the skills as important to resident education. No skills were rated as unimportant to care, out of scope, or unimportant to resident education (median score ≤3). Seventy percent of skills were categorized as “Included.” The domains of Caregiver Support (100%), End of Life Care (66%), and Spiritual/Cultural Assessment and Management (33%) had the highest proportions of skills rated as “Uncertain.” Time limitations (28%) and lack of education (28%) were rated as the main barriers to further integration of palliative care into RO. Conclusions: RO program directors value palliative care skills within RO. The majority of the assessed skills were rated as important to care, within scope of practice, and important to resident education.
Dynamic Assembly of a Feedback Complex to Regulate Oncogenic B-Cell Receptor-Signaling
Authors: Jaewoong Lee, Kohei Kume, Zhengshan Chen, Gang Xiao, Kadriye Nehir Nehir Cosgun, Liting Chen, Lai N Chan, Lars Klemm, Chun-Wei David Chen, Ning Ma, Wing C. Chan, Stephen J Forman, Francesca Zammarchi, Patrick Van Berkel, Ari Melnick, Vu N Ngo, Huimin Geng, Selina M. Luger, Mark Litzow, Michael T McManus, Nagarajan Vaidehi, Elisabeth M. Paietta, Eric Meffre, David M. Weinstock, Markus Müschen
Journal: Blood (2019)
Further Evidence to Monitor Long-term Proton Pump Inhibitor Use
Authors: Kaleen N. Hayes, Nardine R. Nakhla, Mina Tadrous
Journal: JAMA Network Open (2019)

Ana-Maria Vilcu, MSc; Laure Sabatte, MD; Thierry Blanchon, MD, PhD; Cécile Souty, PhD; Milka Maravic, MD, PhD; Magali Lemaitre, PhD; Olivier Steichen, MD, PhD; Thomas Hanslik, MD, PhD
LncRNA-HGBC stabilized by HuR promotes gallbladder cancer progression by regulating miR-502-3p/SET/AKT axis
Authors: Yun-ping Hu, Yun-peng Jin, Xiang-song Wu, Yang Yang, Yong-sheng Li, Huai-feng Li, Shan-shan Xiang, Xiao-ling Song, Lin Jiang, Yi-jian Zhang, Wen Huang, Shi-li Chen, Fa-tao Liu, Chen Chen, Qin Zhu, Hong-zhuan Chen, Rong Shao, Ying-bin Liu
Journal: Molecular Cancer (2019)

Abstract Backgrounds Long non-coding RNAs (lncRNAs) are essential factors that regulate tumor development and metastasis via diverse molecular mechanisms in a broad type of cancers. However, the pathological roles of lncRNAs in gallbladder carcinoma (GBC) remain largely unknown. Here we discovered a novel lncRNA termed lncRNA Highly expressed in GBC (lncRNA-HGBC) which was upregulated in GBC tissue and aimed to investigate its role and regulatory mechanism in the development and progression of GBC. Methods The expression level of lncRNA-HGBC in GBC tissue and different cell lines was determined by quantitative real-time PCR. The full length of lncRNA-HGBC was obtained by 5′ and 3′ rapid amplification of the cDNA ends (RACE). Cellular localization of lncRNA-HGBC was detected by fluorescence in situ hybridization (FISH) assays and subcellular fractionation assay. In vitro and in vivo assays were preformed to explore the biological effects of lncRNA-HGBC in GBC cells. RNA pull-down assay, mass spectrometry, and RNA immunoprecipitation (RIP) assay were used to identify lncRNA-HGBC-interacting proteins. Dual luciferase reporter assays, AGO2-RIP, and MS2-RIP assays were performed to verify the interaction between lncRNA-HGBC and miR-502-3p. Results We found that lncRNA-HGBC was upregulated in GBC and its upregulation could predict poor survival. Overexpression or knockdown of lncRNA-HGBC in GBC cell lines resulted in increased or decreased, respectively, cell proliferation and invasion in vitro and in xenografted tumors. LncRNA-HGBC specifically bound to RNA binding protein Hu Antigen R (HuR) that in turn stabilized lncRNA-HGBC. LncRNA-HGBC functioned as a competitive endogenous RNA to bind to miR-502-3p that inhibits target gene SET. Overexpression, knockdown or mutation of lncRNA-HGBC altered the inhibitory effects of miR-502-3p on SET expression and downstream activation of AKT. Clinically, lncRNA-HGBC expression was negatively correlated with miR-502-3p, but positively correlated with SET and HuR in GBC tissue. Conclusions Our study demonstrates that lncRNA-HGBC promotes GBC metastasis via activation of the miR-502-3p-SET-AKT cascade, pointing to lncRNA-HGBC as a new prognostic predictor and a therapeutic target.
Survival outcomes and prognostic factors in recurrent and/or metastatic head and neck cancer patients treated with chemotherapy plus cetuximab as first-line therapy in a real-world setting
Authors: F. Pontes, I. Rego, I.C. Domingues, L. Pinto, R. Garcia, M.M. Teixeira, L. Khoury, T. Serra, M. Mariano, G.M. Sousa
Journal: Annals of Oncology (2019)
Supplemental MRI Screening for Women with Extremely Dense Breast Tissue
Authors: Marije F. Bakker, Stéphanie V. de Lange, Ruud M. Pijnappel, Ritse M. Mann, Petra H.M. Peeters, Evelyn M. Monninkhof, Marleen J. Emaus, Claudette E. Loo, Robertus H.C. Bisschops, Marc B.I. Lobbes, Matthijn D.F. de Jong, Katya M. Duvivier, Jeroen Veltman, Nico Karssemeijer, Harry J. de Koning, Paul J. van Diest, Willem P.T.M. Mali, Maurice A.A.J. van den Bosch, Wouter B. Veldhuis, Carla H. van Gils
Journal: New England Journal of Medicine (2019)

Extremely dense breast tissue is a risk factor for breast cancer and limits the detection of cancer with mammography. Data are needed on the use of supplemental magnetic resonance imaging (MRI) to improve early detection and reduce interval breast cancers in such patients.In this multicenter, randomized, controlled trial in the Netherlands, we assigned 40,373 women between the ages of 50 and 75 years with extremely dense breast tissue and normal results on screening mammography to a group that was invited to undergo supplemental MRI or to a group that received mammography screening only. The groups were assigned in a 1:4 ratio, with 8061 in the MRI-invitation group and 32,312 in the mammography-only group. The primary outcome was the between-group difference in the incidence of interval cancers during a 2-year screening period.The interval-cancer rate was 2.5 per 1000 screenings in the MRI-invitation group and 5.0 per 1000 screenings in the mammography-only group, for a difference of 2.5 per 1000 screenings (95% confidence interval [CI], 1.0 to 3.7; P<0.001). Of the women who were invited to undergo MRI, 59% accepted the invitation. Of the 20 interval cancers that were diagnosed in the MRI-invitation group, 4 were diagnosed in the women who actually underwent MRI (0.8 per 1000 screenings) and 16 in those who did not accept the invitation (4.9 per 1000 screenings). The MRI cancer-detection rate among the women who actually underwent MRI screening was 16.5 per 1000 screenings (95% CI, 13.3 to 20.5). The positive predictive value was 17.4% (95% CI, 14.2 to 21.2) for recall for additional testing and 26.3% (95% CI, 21.7 to 31.6) for biopsy. The false positive rate was 79.8 per 1000 screenings. Among the women who underwent MRI, 0.1% had either an adverse event or a serious adverse event during or immediately after the screening.The use of supplemental MRI screening in women with extremely dense breast tissue and normal results on mammography resulted in the diagnosis of significantly fewer interval cancers than mammography alone during a 2-year screening period. (Funded by the University Medical Center Utrecht and others; DENSE ClinicalTrials.gov number, NCT01315015.).
Simultaneous targeting of XPO1 and BCL2 as an effective treatment strategy for double-hit lymphoma
Authors: Yuanhui Liu, Nancy G. Azizian, Yaling Dou, Lan V. Pham, Yulin Li
Journal: Journal of Hematology & Oncology (2019)

Abstract Double-hit lymphoma (DHL) is among the most aggressive and chemoresistant lymphoma subtypes. DHLs carry genomic abnormalities in MYC, BCL2, and/or BCL6 oncogenes. Due to the simultaneous overexpression of these driver oncogenes, DHLs are highly resistant to frontline therapies. Most DHLs overexpress both MYC and BCL2 driver oncogenes concurrently. We reasoned that simultaneous suppression of the two driver oncogenes would be more effective in eradicating DHLs than inactivation of single oncogene. XPO1 is a receptor for nuclear cytoplasmic transport of protein and RNA species. Recently, XPO1 inhibition was shown to downregulate MYC expression in several cancer cell lines. We therefore examined the role of XPO1 as a therapeutic target in suppressing MYC function and the potential synergistic effects of simultaneous suppression of XPO1 and BCL2 in the treatment of DHL. Here, we demonstrate that XPO1 inhibition abrogates MYC protein expression and induces massive tumor cell apoptosis. Combined use of XPO1 and BCL2 inhibitors is highly effective in eradicating DHL cells in cell culture. Notably, in a mouse model of DHL bearing primary tumor cells derived from lymphoma patients, combined treatment with XPO1 and BCL2 inhibitors blocks tumor progression, prevents brain metastasis, and extends host survival. Thus, our study confirms the simultaneous targeting of MYC and BCL2 driver oncogenes through the combined use of XPO1 and BCL2 inhibitors as a unique approach for the treatment of DHLs.
Elisabeth Kübler-Ross as Astrophysicist: Emotional Intelligence and Resilience Unlock the Black Hole of Physician Burnout, Moral Distress, and Compassion Fatigue
Authors: Adjoa Boateng, Rebecca Aslakson
Journal: The American Journal of Bioethics (2019)

To the question that Kubler-Ross raises in her seminal text, On Death in Dying, “Are we becoming less human or more human?” (Adams 2019), Childers and Arnold highlight physician challenges in balan...
First analysis of an international pediatric melanoma and atypical melanocytic neoplasm database
Authors: B. J. Averbook, D. Jukic, J. S. Rao, A. Panneerselvam, K. Delman, J. S. Zager, M. Sabel, M. R. Pittelkow, S. Swetter, J. M. Kirkwood
Journal: Journal of Clinical Oncology (2009)

9013 Background: Pediatric melanoma (PM) care has been extrapolated from adult melanoma data. PM and atypical melanocytic neoplasms (AMNs) appear to have different biology. An international database (DB) was developed to clarify their behavior. Methods: IRB approval was obtained at 12 institutions. An SQL-DB was developed for web entry of de-identified demographic and pathologic data for PM and AMN patients (pts) &lt; 21yr through an honest broker system at the University of Pittsburgh. Institutions retained a key of pts entered with assigned numbers for quality assurance and updates. Statistical analysis used Kaplan-Meier survival curves, univariate linear trends and log rank tests. In situ melanoma was excluded from PM survival analysis. Results: 828 pts were registered as of 31 Oct 2008 (ages 11mo-23; median 15yr). 34 pts 21–23yr entered were left in the DB for statistical comparison. Diagnosis years ranged from 1936–2008. 455 pts had complete follow-up. Too few AMN pts had complete follow-up for analysis (18/208). After excluding 32 in situ and 40 with other incomplete data, 365 PM out of 415 total PM were evaluable for OS and 351 for DFS (Stage IV removed). Mean/median age for evaluable PM pts was 16.44/17-yrs (range 1–21yr). 591 pts were age 10–20 while 203 were &lt; 10. Sentinel lymph node (SLN) biopsy showed spread in 30.1 % PM pts (compared to 50% [4/8] of AMN SLN pts). 10-yr PM OS was 80.6%, and pts 0–10 yr had 100% 10-yr OS compared to 69.6% for pts age 10–15 and 79.49% for age 15–20 (p= 0.1473). OS did not differ significantly by gender. Stage predicted OS (p&lt;0.0001). 10-yr OS was 94.13% for Stage I (n=174), 79.62% for stage II (n=67) &amp; 77.14% for stage III (n=75). Thickness affected 10-yr OS: 0–1mm=97% (n=147), 1.1–2mm 70% (n=84), 2.01–4mm 78% (n=71) &amp; &gt;4mm 81% (n=25), p= 0.0099. Survival was similar for pts with PM &gt; 1mm of the several T stage groupings. Ulceration adversely affected OS (p=0.022). Mitosis, defined as present/absent did not alter survival. Nodal metastasis correlated with worse OS (p= 0.170). Conclusions: Stage, thickness, ulceration, and nodal status are significant predictors of OS for PM. Further study will focus on multivariable analysis of PM and AMNs after updating pts, increasing accrual, and cleaning data. No significant financial relationships to disclose.
Dopamine D3 receptor: A neglected participant in Parkinson Disease pathogenesis and treatment?
Authors: Pengfei Yang, Joel S. Perlmutter, Tammie L.S. Benzinger, John C. Morris, Jinbin Xu
Journal: Ageing Research Reviews (2019)

Parkinson disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms which relentlessly and progressively lead to substantial disability and economic burden. Pathologically, these symptoms follow the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) associated with abnormal α-synuclein (α-Syn) deposition as cytoplasmic inclusions called Lewy bodies in pigmented brainstem nuclei, and in dystrophic neurons in striatal and cortical regions (Lewy neurites). Pharmacotherapy for PD focuses on improving quality of life and primarily targets dopaminergic pathways. Dopamine acts through two families of receptors, dopamine D1-like and dopamine D2-like; dopamine D3 receptors (D3R) belong to dopamine D2 receptor (D2R) family. Although D3R's precise role in the pathophysiology and treatment of PD has not been determined, we present evidence suggesting an important role for D3R in the early development and occurrence of PD. Agonist activation of D3R increases dopamine concentration, decreases α-Syn accumulation, enhances secretion of brain derived neurotrophic factors (BDNF), ameliorates neuroinflammation, alleviates oxidative stress, promotes neurogenesis in the nigrostriatal pathway, interacts with D1R to reduce PD associated motor symptoms and ameliorates side effects of levodopa (L-DOPA) treatment. Furthermore, D3R mutations can predict PD age of onset and prognosis of PD treatment. The role of D3R in PD merits further research. This review elucidates the potential role of D3R in PD pathogenesis and therapy.
Progression-Free Survival Analysis of Denosumab Vs Zoledronic Acid in Intent to Transplant Multiple Myeloma Patients Based on Treatment Regimen and Baseline Characteristics
Authors: Evangelos Terpos, Ramón García-Sanz, Kazuyuki Shimizu, Wolfgang Willenbacher, Anthony Glennane, Tian Dai, Walraud Pasteiner, Noopur S. Raje
Journal: Blood (2019)
Complete Response Status According to RECIL 2017 Criteria Shows High Concordance with Lugano 2014 Criteria and Is Highly Prognostic for Outcome in Previously Untreated Patients with CD20-Positive Diffuse Large B-Cell Lymphoma (DLBCL)
Authors: Lale Kostakoglu, Maurizio Martelli, Laurie H Sehn, Marek Trněný, Umberto Vitolo, Andrea Knapp, Federico Mattiello, Tina G Nielsen, Deniz Sahin, Gila Sellam, Carol Ward, Anas Younes
Journal: Blood (2019)
Exercise oscillatory ventilation and prognosis in heart failure patients with reduced and mid‐range ejection fraction
Authors: Sara Rovai, Ugo Corrà, Massimo Piepoli, Carlo Vignati, Elisabetta Salvioni, Alice Bonomi, Irene Mattavelli, Luca Arcari, Angela B. Scardovi, Pasquale Perrone Filardi, Rocco Lagioia, Stefania Paolillo, Damiano Magrì, Giuseppe Limongelli, Marco Metra, Michele Senni, Domenico Scrutinio, Rosa Raimondo, Michele Emdin, Carlo Lombardi, Gaia Cattadori, Gianfranco Parati, Federica Re, Mariantonietta Cicoira, Giovanni Q. Villani, Chiara Minà, Michele Correale, Maria Frigerio, Enrico Perna, Massimo Mapelli, Alessandra Magini, Francesco Clemenza, Maurizio Bussotti, Elisa Battaia, Marco Guazzi, Francesco Bandera, Roberto Badagliacca, Andrea Di Lenarda, Giuseppe Pacileo, Aldo Maggioni, Claudio Passino, Susanna Sciomer, Gianfranco Sinagra, Piergiuseppe Agostoni
Journal: European Journal of Heart Failure (2019)
Professionalism and the Review of Systems
Authors: Julie K. Taitsman
Journal: JAMA (2019)

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Abstract 11346: Effect of Combination Therapy With Ezetimibe and Pitavastatin on Cardiovascular Outcomes in Patients With and Without Hypertension: Findings of the HIJ-PROPER Trial
Authors: Haruki Sekiguchi, Keisuke Suzuki, Jihaeng Im, Masataka Ogiso, Erisa Kawada-Watanabe, Hiroyuki Arashi, Junichi Yamaguchi, Hiroshi Ogawa, Nobuhisa Hagiwara
Journal: Circulation (2018)

Introduction: Lipid-lowering therapy is used for secondary prevention in patients with coronary artery disease, especially those with a history of acute coronary syndrome (ACS). Hypertension (HTN) ...
Integrative molecular and clinical modeling of clinical outcomes to PD1 blockade in patients with metastatic melanoma
Authors: David Liu, Bastian Schilling, Derek Liu, Antje Sucker, Elisabeth Livingstone, Livnat Jerby-Arnon, Lisa Zimmer, Ralf Gutzmer, Imke Satzger, Carmen Loquai, Stephan Grabbe, Natalie Vokes, Claire A. Margolis, Jake Conway, Meng Xiao He, Haitham Elmarakeby, Felix Dietlein, Diana Miao, Adam Tracy, Helen Gogas, Simone M. Goldinger, Jochen Utikal, Christian U. Blank, Ricarda Rauschenberg, Dagmar von Bubnoff, Angela Krackhardt, Benjamin Weide, Sebastian Haferkamp, Felix Kiecker, Ben Izar, Levi Garraway, Aviv Regev, Keith Flaherty, Annette Paschen, Eliezer M. Van Allen, Dirk Schadendorf
Journal: Nature Medicine (2019)

Abstract Immune-checkpoint blockade (ICB) has demonstrated efficacy in many tumor types, but predictors of responsiveness to anti-PD1 ICB are incompletely characterized. In this study, we analyzed a clinically annotated cohort of patients with melanoma ( n = 144) treated with anti-PD1 ICB, with whole-exome and whole-transcriptome sequencing of pre-treatment tumors. We found that tumor mutational burden as a predictor of response was confounded by melanoma subtype, whereas multiple novel genomic and transcriptomic features predicted selective response, including features associated with MHC-I and MHC-II antigen presentation. Furthermore, previous anti-CTLA4 ICB exposure was associated with different predictors of response compared to tumors that were naive to ICB, suggesting selective immune effects of previous exposure to anti-CTLA4 ICB. Finally, we developed parsimonious models integrating clinical, genomic and transcriptomic features to predict intrinsic resistance to anti-PD1 ICB in individual tumors, with validation in smaller independent cohorts limited by the availability of comprehensive data. Broadly, we present a framework to discover predictive features and build models of ICB therapeutic response.