tbuckley/cabot-search huggingface dataset:
An Integrative Approach to Inform Optimal Administration of OX40 Agonist Antibodies in Patients with Advanced Solid Tumors
Authors: Rui Wang, Chan Gao, Megan Raymond, Gennaro Dito, Dominic Kabbabe, Xiao Shao, Ed Hilt, Yongliang Sun, Irene Pak, Martin Gutierrez, Ignacio Melero, Anna Spreafico, Richard D. Carvajal, Michael Ong, Anthony J. Olszanski, Christina Milburn, Kent Thudium, Zheng Yang, Yan Feng, Paula M. Fracasso, Alan J. Korman, Praveen Aanur, Shih-Min A. Huang, Michael Quigley
Journal: Clinical Cancer Research (2019)

The success of checkpoint blockade has led to a significant increase in the development of a broad range of immunomodulatory molecules for the treatment of cancer, including agonists against T-cell costimulatory receptors, such as OX40. Unlike checkpoint blockade, where complete and sustained receptor saturation may be required for maximal activity, the optimal dosing regimen and receptor occupancy for agonist agents is less well understood and requires further study.We integrated both preclinical and clinical biomarker data sets centered on dose, exposure, receptor occupancy, receptor engagement, and downstream pharmacodynamic changes to model the optimal dose and schedule for the OX40 agonist antibody BMS-986178 alone and in combination with checkpoint blockade.Administration of the ligand-blocking anti-mouse surrogate antibody OX40.23 or BMS-986178 as monotherapy or in combination with checkpoint blockade led to increased peripheral CD4+ and CD8+ T-cell activation in tumor-bearing mice and patients with solid tumors, respectively. OX40 receptor occupancy between 20% and 50% both in vitro and in vivo was associated with maximal enhancement of T-cell effector function by anti-OX40 treatment, whereas a receptor occupancy > 40% led to a profound loss in OX40 receptor expression, with clear implications for availability for repeat dosing.Our results highlight the value of an integrated translational approach applied during early clinical development to aggregate preclinical and clinical data in an effort to define the optimal dose and schedule for T-cell agonists in the clinic.
Predictive value of neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) In hepatocellular carcinoma (HCC) patients treated with nivolumab (N)
Authors: S. Dharmapuri, U. Özbek, J.-Y. Lin, M. Schwartz, A. Branch, C. Ang
Journal: Annals of Oncology (2019)
Local ablative treatment and treatment beyond progression for oligo-progression in stage IV non-small cell lung cancer after tumour response to anti-PD1 treatment
Authors: F. Guisier, R. Gervais, K El Husseini, J.-B. Assié, M. Geier, C. Decroisette, R. Corre, R. Descourt, C. Chouaid, M. Salaun, L. Thiberville
Journal: Annals of Oncology (2019)
Consultant who claimed money for work he didn’t do gets 12 month suspension
Authors: Clare Dyer
Journal: BMJ (2019)

A consultant anaesthetist who dishonestly added his name to operation charge sheets so as to collect pay he had not earned has been suspended from the UK medical register for 12 months.

Pandeshwar Gururaj, who qualified in India in 1986, was a consultant anaesthetist at NHS Grampian but also practised at the private BMI Healthcare Albyn Hospital. There, in February 2018, a senior theatre practitioner saw him writing on charge sheets in theatre. Asked what he was doing, he replied that he was “sending the charge sheets to recovery.”

The handling of these documents was not his job, and when the theatre practitioner looked at them later she saw that his name had been added for a procedure he had not attended. She alerted her superiors.

Gururaj …
Works by eminent psychologist who doubted smoking caused cancer are “unsafe,” finds inquiry
Authors: Nigel Hawkes
Journal: BMJ (2019)

An inquiry into the work of Hans Eysenck, who dominated the profession of psychology in the UK in the mid-20th century, has determined that 26 of his papers are “unsafe” and that the editors of the 11 journals where they were published should be informed of the finding.

King’s College London launched the inquiry after an appeal from the editor of the Journal of Health Psychology , David Marks. The disputed papers were all published late in Eysenck’s career, in collaboration with Ronald Grossarth-Maticek, a German sociologist who provided a body of data from which he and Eysenck drew some eyebrow raising conclusions.

The inquiry report, which is brief, was compiled by a team from the Institute of Psychiatry, Psychology and Neuroscience at King’s College who do not reveal their names. Its message is that the critics of this series of papers, most notably …
Risk factors for development of severe liver disease in more than 400 000 patients with type 2 diabetes: A population-based cohort study
Authors: K. Björkström, S. Franzén, B. Eliasson, M. Miftaraj, S. Gudbjornsdottir, Y. Trolle-Lagerros, A.-M. Svensson, H. Hagström
Journal: Journal of Hepatology (2018)
The Role Of Intraplatelet Reactive Oxygen Species In The Regulation Of Platelet Glycoprotein Ibα Ectodomain Shedding
Authors: Pingping Zhang, Juan Du, Lili Zhao, Xiujuan Wang, Yiwen Zhang, Rong Yan, Jin Dai, Guanglei Liu, Feng Zhang, Kesheng Dai
Journal: Blood (2013)
Flexible Multielectrode Array for Skeletal Muscle Conditioning, Acetylcholine Receptor Stabilization and Epimysial Recording After Critical Peripheral Nerve Injury
Authors: Malia McAvoy, Jonathan K Tsosie, Keval N Vyas, Omar F Khan, Kaitlyn Sadtler, Robert Langer, Daniel G Anderson
Journal: Theranostics (2019)

Complete re-innervation after a traumatic injury severing a muscle's peripheral nerve may take years. During this time, the denervated muscle atrophies and loses acetylcholine receptors, a vital component of the neuromuscular junction, limiting functional recovery. One common clinical treatment for atrophy is electrical stimulation; however, epimysial electrodes currently used are bulky and often fail due to an excessive inflammatory response. Additionally, there remains a need for a device providing in vivo monitoring of neuromuscular regeneration and the maintenance of acetylcholine receptors. Here, an implantable, flexible microelectrode array (MEA) was developed that provides surface neuromuscular stimulation and recording during long-term denervation. Methods: The MEA uses a flexible polyimide elastomer and an array of gold-based microelectrodes featuring Peano curve motifs, which together maintain electrode flexibility. The devices were implanted along the denervated gastrocnemius muscles of 5 rats. These rats underwent therapeutic stimulation using the MEA daily beginning on post-operative day 2. Another 5 rats underwent tibial nerve resection without implantation of MEA. Tissues were harvested on post-operative day 14 and evaluated for quantification of acetylcholine receptors and muscle fiber area using immunofluorescence and histological staining. Results: The Young's modulus was 1.67 GPa, which is comparable to native tendon and muscle. The devices successfully recorded electromyogram data when implanted in rats. When compared to untreated denervated muscles, MEA therapy attenuated atrophy by maintaining larger muscle fiber cross-sectional areas (p < 0.05). Furthermore, the acetylcholine receptor areas were markedly larger with MEA treatment (p < 0.05). Conclusions: This proof-of-concept work successfully demonstrates the ability to combine conformability, tensile strength-enhancing metal micropatterning, electrical stimulation and recording into a functional implant for both epimysial stimulation and recording.
Time to second progression (PFS2) and second subsequent therapy (TSST) for patients (pts) with newly diagnosed, advanced ovarian cancer (OC) and a BRCA mutation (BRCAm) treated with maintenance (mt) olaparib (ola): Phase III SOLO1 trial
Authors: A. Oaknin, K. Moore, N. Colombo, G. Scambia, B.-G. Kim, M. Friedlander, A. Lisyanskaya, A. Floquet, A. Leary, G.S. Sonke, C. Gourley, S. Banerjee, A.M. Oza, A. González-Martín, C. Aghajanian, W. Bradley, E.S. Lowe, R. Bloomfield, P. DiSilvestro
Journal: Annals of Oncology (2019)
Lipopolysaccharide-anchored macrophages hijack tumor microtube networks for selective drug transport and augmentation of antitumor effects in orthotopic lung cancer
Authors: Ling Guo, Ye Zhang, Runxiu Wei, Cuifeng Wang, Min Feng
Journal: Theranostics (2019)

Objective: Engineered immune cells (e.g., therapeutic T cells) provide a revolutionary approach to combat cancer.Certain activated immune cells can exquisitely sense and respond to the tumor microenvironment.Here, we propose a paradigm based on engineering macrophages to allow selective intercellular drug delivery and augmentation of antitumor activities by hijacking tumor microtube networks.Methods: Macrophages were engineered via anchoring lipopolysaccharides on the plasma membrane (LM).The tumor tropism of LM encapsulating doxorubicin (LM-Dox) was monitored by a real-time cell migration assay and small animal in vivo imaging.Monocyte chemoattractant protein-1 (CCL2) was measured by quantitative PCR and ELISA.Intercellular conduit formation was characterized by confocal laser scanning microscopy and scanning electron microscopy.LM-Dox activation of tumor-associated macrophages to release TNF-α was evaluated by western blot and immunofluorescence assays.The potential therapeutic effects of LM-Dox in a 3D tumor-immune model and a murine orthotopic lung cancer model were tested.Results: LM-Dox exhibited tumor tropism in response to CCL2 produced by A549 lung tumor cells and lung tumor tissues resulting in a remarkably higher amount of tumor accumulation than the case of Lipo-Dox (~ 4-fold).Intriguingly, LM-Dox accumulated at tumor sites hijacked the established tumor microtube networks and even stimulated microtube formation with tumor cells but not with normal cells to enable selective and rapid transport of the drug to tumor cells.Simultaneously, LM-Dox induced secretion of TNF-α in tumor-associated macrophages, which increased the antitumor activity of Dox.Thus, LM-Dox increased the inhibitory effects on tumor growth and metastasis in a mouse orthotopic lung cancer model and minimized the side effects of Dox-induced tumor invasion. Conclusion:Lipopolysaccharide-anchored macrophages that can hijack tumor microtube networks for selective drug transport may serve as versatile bioactive carriers of anticancer drugs.In the clinical context, these engineered microphages represent a personalized medicine approach that can be translated into potential use of patient-derived monocytes/macrophages for drug delivery by means of cell-to-cell communication.
External validation and longitudinal extension of the LIPI (Lung Immune Prognostic Index) for immunotherapy outcomes in advanced non-small cell lung cancer
Authors: J.M. Riedl, D.A. Barth, V. Foris, F. Posch, S. Mollnar, M. Stotz, M. Pichler, H. Stöger, G. Absenger, H. Olschewski, A. Gerger
Journal: Annals of Oncology (2019)
TP53 hotspot mutations as immunoreactive neoantigens define a signature with differential survival outcomes in advanced ovarian cancer
Authors: M. Garziera, E. Cecchin, J. Polesel, V. Canzonieri, R. Sorio, S. Gagno, S. Scalone, R. Roncato, E. De Mattia, E. Poletto, G. Giorda
Journal: Annals of Oncology (2019)
Initial results from TROPHY-U-01: A phase II open-label study of sacituzumab govitecan in patients (Pts) with metastatic urothelial cancer (mUC) after failure of platinum-based regimens (PLT) or immunotherapy
Authors: S.T. Tagawa, A. Balar, D.P. Petrylak, P. Grivas, N. Agarwal, C.N. Sternberg, Q. Hong, A. Gladden, C. Kanwal, P. Siemon-Hryczyk, T. Goswami, L.M. Itri, Y. Loriot
Journal: Annals of Oncology (2019)
Invasive fungal diseases caused by rare pathogens in patients after hematopoietic stem cell transplantation (HSCT) & chemotherapy
Authors: Y. Rogacheva, M. Popova, A. Volkova, A. Frolova, I. Markova, I. Nikolaev, S. Ignatieva, T. Bogomolova, A. Gevorgian, O. Paina, T. Bykova, E. Darskaya, O. Goloshchapov, E. Morozova, M. Vladovskaya, S. Bondarenko, I. Moiseev, L. Zubarovskaya, N. Klimko, B. Afanasyev
Journal: Annals of Oncology (2019)
GOLFIG chemo-immunotherapy in metastatic colorectal cancer (mCRC) patients: A fifteen year retrospective analysis
Authors: P. Correale, N. Staropoli, P. Pastina, R. Giannicola, C. Botta, E. Francini, L. Ridolfi, E. Mini, D. Ciliberto, R.M. Agostino, A. Strangio, D. Azzarello, V. Nardone, A. Falzea, P. Tassone, A. Giordano, L. Pirtoli, G. Francini, P.S. Tagliaferri
Journal: Annals of Oncology (2019)
Multiparametric Magnetic Resonance Imaging for the Detection of Clinically Significant Prostate Cancer: What Urologists Need to Know. Part 2: Interpretation
Authors: Bas Israël, Marloes van der Leest, Michiel Sedelaar, Anwar R. Padhani, Patrik Zámecnik, Jelle O. Barentsz
Journal: European Urology (2019)

There is large variability among radiologists in their detection of clinically significant (cs) prostate cancer (PCa) on multiparametric magnetic resonance imaging (mpMRI).To reduce the interpretation variability and achieve optimal accuracy in assessing prostate mpMRI.How the interpretation of mpMRI can be optimized is demonstrated here. Whereas part 1 of the "surgery-in-motion" paper focused on acquisition, this paper shows the correlation between (ab)normal prostate anatomical structures and image characteristics on mpMRI, and how standardized interpretation according to Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) should be performed. This will be shown in individual patients.To detect csPCa, three mpMRI "components" are used: "anatomic" T2-weighted imaging, "cellular-density" diffusion-weighted imaging, and "vascularity" dynamic contrast-enhanced MRI.Based on PI-RADS v2, the accompanying video shows how mpMRI interpretation is performed. Finally, the role of mpMRI in detecting csPCa is briefly discussed and the main features of the recently introduced PI-RADS v2.1 are evaluated.With PI-RADS v2, it is possible to quantify normal and abnormal anatomical structures within the prostate based on its imaging features of the three mpMRI "components." With this knowledge, a more objective evaluation of the presence of a csPCa can be performed. However, there still remains quite some space to reduce interobserver variability.For understanding the interpretation of mpMRI according to PI-RADS v2, knowledge of the correlation between imaging and (ab)normal anatomical structures on the three mpMRI components is needed.This second surgery-in-motion contribution shows what structures can be recognized on prostate magnetic resonance imaging (MRI). How a radiologist performs his reading according to the so-called Prostate Imaging Reporting and Data System criteria is shown here. The main features of these criteria are summarized, and the role of prostate MRI in detecting clinically significant prostate cancer is discussed briefly.
Phase II study of preoperative (PREOP) chemoradiotherapy (CTRT) plus avelumab (AVE) in patients (PTS) with locally advanced rectal cancer (LARC): The AVANA Study
Authors: L. Salvatore, M. Bensi, F. Pietrantonio, A. Boccaccino, C. Barbara, A. Auriemma, M. Ratti, E. Tamburini, R. Bordonaro, M. Clavarezza, A. Avallone, F. Bergamo, C. Granetto, S. Bustreo, F Di Fabio, V. Smiroldo, B. Corvari, G. Tortora
Journal: Annals of Oncology (2019)
Surveillance for Violent Deaths — National Violent Death Reporting System, 27 States, 2015
Authors: Shane P.D. Jack, Emiko Petrosky, Bridget H. Lyons, Janet M. Blair, Allison M. Ertl, Kameron J. Sheats, Carter J. Betz
Journal: MMWR Surveillance Summaries (2018)

In 2015, approximately 62,000 persons died in the United States as a result of violence-related injuries. This report summarizes data from CDC's National Violent Death Reporting System (NVDRS) regarding violent deaths from 27 U.S. states for 2015. Results are reported by sex, age group, race/ethnicity, location of injury, method of injury, circumstances of injury, and other selected characteristics.
Prescription and treatment patterns of lenvatinib (L) in patients with radioactive iodine-refractory differentiated thyroid cancer (rDTC): A retrospective analysis of the Canadian Patient Support Program (PSP)
Authors: S.J. Hotte, E. Winquist, B. Lemieux, S.A. Laurie, N. Bouganim, N. Chua, M. Brassard, J.D. Ruether, N. Lamond, S. Ezzat, P. Klimo, H. Lim, M.-H. Massicotte, R. Wong, P. Lam, B. Yap, M.K. Krzyzanowska
Journal: Annals of Oncology (2019)
Comprehensive molecular characterization of brain metastases (BM) from colorectal cancer (CRC)
Authors: F. Battaglin, J. Xiu, Y. Baca, R.M. Goldberg, A. Grothey, A.F. Shields, A. Seeber, M.E. Salem, A. Puccini, R. Tokunaga, M. Naseem, H. Arai, J. Wang, M.D. Berger, W. Zhang, P.A. Philip, J.L. Marshall, W.M. Korn, H.J. Lenz
Journal: Annals of Oncology (2019)
PD-L1 expression in primary tumour vs metastatic samples in the phase III MYSTIC study in first-line metastatic (m) NSCLC
Authors: N. Reinmuth, A.-M. Boothman, B.C. Cho, K.H. Lee, A. Luft, M.-J. Ahn, M. Scott, J. Whiteley, J. Walker, V. Karwe, P. Mukhopadhyay, P. Thiyagarajah, U. Scheuring, N. Rizvi
Journal: Annals of Oncology (2019)
Phase I open-label study evaluating the safety, pharmacokinetics, and preliminary efficacy of ABBV-181 and rovalpituzumab tesirine (ROVA-T) in patients with small cell lung cancer
Authors: E. Calvo, A. Spira, H. Prenen, Y. Ohe, S. Rottey, A. Gazzah, M. Millward, V. Moreno, A. Italiano, T. Alanko, K. Yoh, P.A. Cassier, T. Seto, D. Afar, S. Englert, P. Komarnitsky, S. Lambert, A. Parikh, G. Vosganian, B. Gao
Journal: Annals of Oncology (2019)
The prevalence of abnormal cervical cytology among postnatal clinic attendees at the University of Calabar Teaching Hospital, Calabar, Nigeria.
Authors: Boniface Uji Ago
Journal: Journal of Clinical Oncology (2013)

e12568 Background: Carcinoma of the uterine cervix is a deadly but preventable disease. It is still a major gynecologic problem in our subregion. Cervical cytology remains the key to its early detection and prompt treatment. Methods: This was a prospective cross sectional study of postnatal women to determine the prevalence of abnormal cervical cytology and their socio-demographic characteristics. Institutional ethical clearance and informed consent of participants were obtained. Aye's spatula and endocervical brush were used to collect specimen from the ectocervix and endocervix respectively and smeared on individually labelled glass slides. The samples were treated using the conventional Papanicolaou staining method and reported using the Bethesda system. Researcher-administered questionnaire generated data as well as results of cytology were analyzed using Epi-Info version 3.5.1.0 (CDC Atlanta USA 2008). Results: There were 100 women screened. Three percent had low grade squamous intraepithelial lesion. Colposcopy done, however, did not reveal abnormal findings. Ninety-five percent of the women had no prior knowledge of cervical cancer and Pap smear. Two percent of the women had a family history of cervical cancer and both patients died of the disease due to lack of facilities for treatment. Conclusions: Cervical cancer is a preventable disease. Women in our subregion are under-screened. Effective screening methods are the mainstay in its prevention. Availability of well equipped gynecologic oncology centers with personnel training are a necessary end to this carnage.
B-YOND Final Results Confirm Established Safety, Sustained Efficacy, and Extended Dosing Interval for Up to 4 Years of Treatment With rFIXFc in Previously Treated Subjects With Severe Hemophilia B
Authors: Margaret Ragni, Roshni Kulkarni, K. John Pasi, Kathelijn Fischer, Johnny Mahlangu, Amy Shapiro, Beatrice Nolan, Johannes Oldenburg, Tadashi Matsushita, Annemieke Willemze, Huixing Yuan, Dan Rudin
Journal: Blood (2018)
Clonal hematopoiesis mutations in plasma cfDNA RAS/BRAF genotyping of metastatic colorectal cancer
Authors: B. Wang, F. Huang, M. Shen, S. Wu, H. Wang, H. Jiang, Y. Yu, Q. Yu, Y. Yang, Y. Zhao, Y. Zhou, B. Pan, T. Liu, W. Guo
Journal: Annals of Oncology (2019)
Abstract P5-07-10: The prognostic significance of estrogen formation as a consequence of aromatase expression in tumor microenvironment
Authors: TH Kim, A Lee, JW Han, SJ Jung, K-D Byun
Journal: Cancer Research (2019)

Abstract Estrogen synthesis via aromatase in adipose tissue has an important role in progression of postmenopausal breast cancer. The increased local concentrations of estrogen in breast cancer via aromatase overexpression within the tumor tissue have been demonstrated by some investigators. Although aromatase inhibitor is the standard endocrine therapy for postmenopausal breast cancer patients, it is not uncommon for patients to have poor compliance to the drugs due to their side effects. This research is based on the hypothesis that if aromatase expression is related to prognosis and if therapeutic effect varies depending on the degree of aromatase expression, then this study may be able to suggest a new guideline in terms of choosing between aromatase inhibitors and tamoxifen. Methods: 154 postmenopausal breast cancer patients who underwent surgery and aromatase inhibitor therapy in Busan Paik Hospital, Inje University from January 2005 to December 2010 were enrolled. Patients with DCIS or stage IV breast cancer were excluded. Patients' clinicopathological data were collected and TMA blocks were created for immunohistochemistry studies to examine aromatase expression. Results: The recurrence has occured in 7 patients (6.9%). Stage, tumor size and number of lymph node metastasis were related to increased risk of recurrence (p=0.051, 0.043, 0.001). The aromatase expression in cancer cells had significant correlation with clinical stage (p=0.041). There was also a positive correlation between Ki67 and aromatase expression in cancer tissue (p=0.006). However, aromatase expression in cancer, stromal, and adipose tissue had no relationship with recurrence (p=0.410, 0.627, 0.552). Correlation between clinicopathologic factors and aromatase expression (Linear by linear association and Spearman's correlation coefficient test)Site of aromatase expressionERPRKi67P53BMIStageIn Cancer0.6060.5920.0060.4510.9560.041In Stroma0.2200.4710.5840.3290.3670.229In Adipose0.9880.2650.1590.1170.7701.000 Conclusions: Aromatase expression in cancer cells was correlated with clinical stage. This implies that aromatase expression might have a role of prognostic marker in addition to role of treatment indicator. There was no direct correlation between aromatase expression and recurrence. Citation Format: Kim TH, Lee A, Han JW, Jung SJ, Byun K-D. The prognostic significance of estrogen formation as a consequence of aromatase expression in tumor microenvironment [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-07-10.
Evaluation of markers associated with efficacy of abiraterone acetate plus prednisone (AAP) in patients (pts) with castration-sensitive prostate cancer (mCSPC) from the LATITUDE study
Authors: K.N. Chi, S. Thomas, M. Gormley, D. Shen, S. Joshi, N. Tran, M. Smith, D. Ricci, K. Fizazi
Journal: Annals of Oncology (2019)