tbuckley/cabot-search huggingface dataset:
CT image standardization is superior to larger but heterogeneous data for robust radiomic models
Authors: D. Vuong, M. Bogowicz, J. Unkelbach, R. Foerster, S. Denzler, A. Xyrafas, M. Pless, S. Thierstein, S. Peters, M. Guckenberger, S. Tanadini-Lang
Journal: Annals of Oncology (2019)

Background: Radiomics is a promising tool for identification of new prognostic biomarkers. Radiomic models are often based on single-institution data however multi-centric data, highly heterogeneous due to different scanning protocols, reflect better the clinical reality. Robustness studies are crucial to find features robust to e.g. scanner settings. We study if a CT radiomics overall survival (OS) model trained on multi-centric data with robust feature pre-selection can achieve a similar performance as a model on standardized data. Methods: Pre-treatment CT data from 121 IIIA/N2 NSCLC patients from a prospective multi-centric randomized trial (SAKK 16/00, neoadj. chemo- or radiochemotherapy prior to surgery) were used to calculate 1404 radiomic features on the primary tumor. Two OS radiomic models were trained on (1) a sub-cohort with standardized imaging protocol (native CT, standard kernel, n = 84) and on (2) the entire heterogeneous cohort but with robust radiomic feature pre-selection. Robust features were extracted from four robustness studies (contrast, convolution kernel, motion, delineation) using the intra-class correlation coefficient (> 0.9 considered stable). Seperately for each model, principal component (PC) analysis was performed and PCs describing in total 95% data variance were selected. The feature with highest correlation to the PCs were used for the multivariate Cox model with backward selection. Model performances were quantified using Concordance Index (CI), verified with 10-fold cross-validation and compared using bootstrap with resampling. Results: Robustness studies revealed 113 stable features. The convolution kernel was the largest influence on the feature stability. Final OS model on the entire heterogeneous data consisted of four and on standardized data of six features (all identified as unstable). The model on standardized data showed significant better prognostic performance compared to the model with robust feature pre-selection based on the entire heterogeneous data (CI = 0.64 and 0.61, p < 0.05, resp.). Conclusions: For our prognostic NSCLC radiomic models image protocol standardization appears superior to using larger but heterogeneous imaging data combined with robust feature pre-selection. Legal entity responsible for the study: The authors. Funding: Swiss National Science Foundation (SNSF) Swiss Group for Clinical Cancer Research SAKK. Disclosure: M. Guckenberger: Board member: European Society for Therapeutic Radiation Oncology (ESTRO). All other authors have declared no conflicts of interest.
TCTAP C-216 Effect of Breath Holding on Coronary Stenosis Sandwiched Between Aorta and Pulmonary Artery Assessed with Intravascular Ultrasound and Fractional Flow Reserve
Authors: Yusuke Nakano, Tajima Atomu, Katsuhisa Waseda, Mayu Suzuki, Hirofumi Ohashi, Hirohiko Ando, Hiroaki Takashima, Tetsuya Amano
Journal: Journal of the American College of Cardiology (2019)
The Circadian Clock Gene <i>Bmal1</i> Controls Intestinal Exporter MRP2 and Drug Disposition
Authors: Fangjun Yu, Tianpeng Zhang, Cui Zhou, Haiman Xu, Lianxia Guo, Min Chen, Baojian Wu
Journal: Theranostics (2019)

The intestinal exporter MRP2 plays an important role in disposition and elimination of a wide range of drugs.Here, we aimed to clarify the impact of circadian clock on intestinal MRP2, and to determine the molecular mechanisms for generation of diurnal MRP2 expression. Methods:The regulatory effects of Bmal1 on intestinal MRP2 expression were assessed using intestine-specific Bmal1 knockout (Bmal1 iKO ) mice and colon cancer cells.The relative mRNA and protein levels were determined by qPCR and Western blotting, respectively.Everted gut sac, cell viability and in situ intestinal perfusion experiments were performed to evaluate intestinal efflux of the MRP2 substrate methotrexate (MTX).Toxicity and pharmacokinetic experiments were performed with Bmal1 iKO mice and control littermates (Bmal1 fl/fl mice) after oral gavage of MTX.Transcriptional gene regulation was investigated using luciferase reporter, mobility shift and chromatin immunoprecipitation (ChIP) assays.Results: Bmal1 iKO mice were generated by inter-crossing the mice carrying a Bmal1 exon 8 floxed allele (Bmal1 fl/fl ) with Villin-Cre mice.Intestinal MRP2 expression exhibited a diurnal oscillation in Bmal1 fl/fl mice with a zenith value at ZT6. Bmal1 ablation caused reductions in Mrp2 mRNA and protein levels [as well as in transport activity (measured by MTX)], and blunted their diurnal rhythms.Intestinal ablation of Bmal1 abrogated circadian time-dependency of MTX pharmacokinetics and toxicity.Bmal1/BMAL1 regulation of rhythmic Mrp2/MRP2 expression was also confirmed in the colon cancer CT26 and Caco-2 cells.Based on a combination of luciferase reporter, mobility shift and ChIP assays, we found that Dbp activated and E4bp4 repressed Mrp2 transcription via specific binding to a same D-box (-100/-89 bp) element in promoter region.Further, Bmal1 directly activated the transcription of Dbp and Rev-erbα through the E-boxes, whereas it negatively regulated E4bp4 via the transcriptional repressor Rev-erbα.Positive regulation of Mrp2 by Rev-erbα was also observed, and attained through modulation of E4bp4. Conclusion:Bmal1 coordinates temporal expressions of DBP (a MRP2 activator), REV-ERB (an E4BP4 repressor) and E4BP4 (a MRP2 repressor), generating diurnal MRP2 expression.
Paracetamol for dengue fever: no benefit and potential harm?
Authors: Jacqueline Deen, Lorenz von Seidlein
Journal: The Lancet Global Health (2019)

Dengue fever is a mosquito-borne illness that is highly endemic in tropical areas of Asia and Latin America. An estimated 58·4 million (23·6–121·9) symptomatic dengue infections occur annually, resulting in about 10 000 deaths per year.1 These estimates show a dramatic increase in dengue incidence during the past two decades, with the number of symptomatic dengue infections more than doubling every 10 years between 1990 and 2013.1
Safety of biosimilar filgrastim in elderly patients undergoing neutropenia-inducing chemotherapy: a subanalysis of the NEXT study.
Authors: Didier Kamioner, Frederic Maloisel, Stephane Leprêtre, Christian Berthou, Helene Albrand
Journal: Journal of Clinical Oncology (2015)

9541 Background: Febrile neutropenia (FN) is a serious and frequent complication of cytotoxic chemotherapy (CT), especially in elderly patients (pts). Biosimilar filgrastim (Nivestim, Hospira Inc.) is a granulocyte-colony stimulating factor (G-CSF) licensed for the treatment of neutropenia and FN induced by myelosuppressive CT. This subanalysis of the NEXT (Nivestim safety profile in patiEnts treated with cytotoXic in real-life clinical pracTice) study explored tolerability and efficacy of biosimilar G-CSF in elderly pts. Methods: NEXT was a prospective, non-interventional, longitudinal, multicentre study conducted in France to evaluate the safety of biosimilar filgrastim. Recorded data included pt demographic and clinical characteristics, biosimilar filgrastim treatment-related data on efficacy and safety, such as adverse events (AEs) and FN. Pts were monitored for 1–6 CT cycles with three visits at inclusion, during treatment, and following CT. Here we present a subanalysis of pts aged ≥ 70 years. Results: Overall, 2114 pts were enrolled in the study; this subanalysis includes 708 pts aged ≥ 70 years (55.9% male; mean age ± standard deviation (SD) 76.3±4.7 years; performance status rated 3 or 4:10.5%; 68.2% solid tumours; 31.8% haematological malignancies). The majority (98.3%) of pts received prophylactic biosimilar filgrastim (primary prophylaxis: 91.7%; secondary prophylaxis: 8.3%).For pts receiving prophylactic biosimilar filgrastim, the median time to treatment initiation was 2 days after the last CT dose; mean treatment duration ± SD was 6.1±4.3 days. In this subanalysis, 18.9% of pts had ≥ 1 AE with 11.4% of pts reporting muscle and/or bone disorders. During the study, 4.5% and 3.0% of pts had FN and infection respectively (vs 4.9% and 3.1% in the overall population). FN and/or infection led to hospitalisation of 3.5% of pts (mean duration ± SD: 11.6±15.6 days), a CT dose reduction in 3.6% of pts and a delay in administration of CT in 7.0% of pts. Conclusions: Biosimilar filgrastim was effective and well tolerated in in the treatment and prevention of FN in the elderly and is an alternative therapeutic option for pts with CT-induced neutropenia. Clinical trial information: NCT01574235.
Current status of autologous stem cell transplantation for multiple myeloma
Authors: Rama Al Hamed, Abdul Hamid Bazarbachi, Florent Malard, Jean-Luc Harousseau, Mohamad Mohty
Journal: Blood Cancer Journal (2019)

Abstract More than 30 years after its introduction, autologous stem cell transplantation (ASCT) remains the standard of care for young patients with newly diagnosed multiple myeloma. Not only did the arrival of novel agents such as immunomodulatory drugs (IMiDs), proteasome inhibitors (PI) and monoclonal antibodies not replace ASCT, instead they solidified its central role as standard of care. Novel agent use is now inarguably essential in induction, maintenance, and possibly consolidation. In light of these new advancements, new challenges arise in deciding on optimal practice. Who is most suited to undergo ASCT? Is there an age threshold that should not be surpassed? Should transplantation be embarked on early or is it reasonable to delay it? What are the optimal induction, consolidation, and maintenance therapies? What is the role of tandem transplantation in the era of novel agents and where do patient-specific cytogenetics come into the equation when deciding on treatment? These are some of the questions addressed in this review which we will attempt to answer with the latest currently available data.
PS-166-Repopulation of decellularized porcine bile ducts with human cholangiocyte organoids for the generation of human-sized bioengineered biliary tissue
Authors: Teresa Brevini, Walid Al-Akkad, Alessandro F Pellegata, Olivia C Tysoe, Luca Frenguelli, Si Emma Chen, Paolo De Coppi, Massimo Pinzani, Kourosh Saeb-Parsy, Ludovic Vallier, Giuseppe Mazza, Fotios Sampaziotis
Journal: Journal of Hepatology (2019)
Non-small cell lung cancer in the elderly: A retrospective study comparing first-line treatment with single-agent vs combination chemotherapy vs tyrosine kinase inhibitor
Authors: É. Cipriano, A. Tavares, A. Soares, F. Estevinho, C. Sottomayor
Journal: Annals of Oncology (2019)

Background: Lung cancer has a high incidence in elderly patients. These patients are more predisposed to therapeutic toxicities, drug interactions and limitations due to physiologic alterations and comorbidities. The use of single-agent versus combination chemotherapy (ChT) as a first line treatment in this group of patients continues to be debated. The objective of this study is to characterise elderly patients diagnosed with lung cancer at our institution and evaluate overall survival (OS) in this population. Methods: This was a retrospective study of patients with first multidisciplinary discussion between 01/01/2015 and 31/12/2017, aged ≥ 70 years at the time of diagnosis and non-small cell cancer (NSCLC) histology. The population was characterized and a survival analysis (Kaplan-Meier; Log Rank test; statistical significance 5%) was performed, with a follow-up period until 30/11/2018. Results: We identified 293 patients with lung cancer, 112 with an age ≥ 70 years (38,2%) and 98 of these patients (87,5%) with NSCLC histology. Fifty-three (54,1%) had an ECOG 0-1 and 25 (25,5%) an ECOG 2. At the time of diagnosis, 65 (66,3%) had stage IV, 9 (9,2%) stage III and 24 (24,5%) stage I-II. Forty-six patients (46,9%) were treated with systemic therapy (ST) due to locally advanced or stage IV disease; 24,5% (n=24) received surgery (with or without adjuvant ChT) or radiotherapy and 28,6% (n=28) received best supportive care (BSC). During a median follow-up of 30,9 months (mo.), median OS in patients treated with ST was 10,3 mo. (CI 95% 7,80-12,80), compared to 1,9 mo. (CI 95% 1,12-2,68) in patients receiving BSC, p < 0,0001. Regarding first line treatment in patients treated with ST, 22 (47,8%) received single-agent ChT, 16 (34,8%) received a doublet ChT, and 8 (17,4%) a tyrosine kinase inhibitor (TKI). Median OS was 8,3 mo. (CI 95% 3,70-12,90), 10,3 mo. (CI 95% 4,62-15,98) and 12,3 mo. (CI 95% 4,70 – 19,90), p=0,469, respectively. Conclusions: More than 1/3 of patients with lung cancer are elderly and nearly half of this population was treated with ST due to locally advanced or stage IV disease. Patients with advanced NSCLC receiving ST had a superior OS compared to patients receiving only BSC. The differences in OS between patients treated with single-agent, doublet ChT and TKI in first line were not statistical significant. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Comparative analysis of sequencing technologies for single-cell transcriptomics
Authors: Kedar Nath Natarajan, Zhichao Miao, Miaomiao Jiang, Xiaoyun Huang, Hongpo Zhou, Jiarui Xie, Chunqing Wang, Shishang Qin, Zhikun Zhao, Liang Wu, Naibo Yang, Bo Li, Yong Hou, Shiping Liu, Sarah A. Teichmann
Journal: Genome biology (2019)

Single-cell RNA-seq technologies require library preparation prior to sequencing. Here, we present the first report to compare the cheaper BGISEQ-500 platform to the Illumina HiSeq platform for scRNA-seq. We generate a resource of 468 single cells and 1297 matched single cDNA samples, performing SMARTer and Smart-seq2 protocols on two cell lines with RNA spike-ins. We sequence these libraries on both platforms using single- and paired-end reads. The platforms have comparable sensitivity and accuracy in terms of quantification of gene expression, and low technical variability. Our study provides a standardized scRNA-seq resource to benchmark new scRNA-seq library preparation protocols and sequencing platforms.
THU-420-Examination of patient and provider perceptions of hepatitis C care in Rwanda
Authors: janvier serumondo, Alida Ngwije, michael penkunas, Justine Umutesi, julienne niyikora, sabine umuraza, Gentille Musengimana, colton halverson, Makuza Jean Damascene, clarisse musanabaganwa, Prosper Karame, cyprien ntirenganya, Soline Mugeni, Athanase Kiromera, Sabin Nsanzimana
Journal: Journal of Hepatology (2019)
FRI-382-Biological assessment comprising alpha-fetoprotein, albuminbilirubin score and C-reactive protein provides better prognostic competence than tumor size criteria in liver transplant patients with HCC
Authors: Arno Kornberg, Martina Achernhammer, Jennifer Kornberg, Katharina Müller, Helmut Friess, Katharina Thrum
Journal: Journal of Hepatology (2019)
Cytomegalovirus: an unrecognised potential contributor to cystic fibrosis disease progression?
Authors: Michael D. Parkins, Kathleen J. Ramos, Christopher H. Goss, Ranjani Somayaji
Journal: European Respiratory Journal (2019)

<b>Of cystic fibrosis (CF) patients referred for lung transplant consideration, those who are cytomegalovirus (CMV) IgG<sup>+</sup> at referral are 8 years younger than seronegatives, suggesting CMV may have a pathogenic role in CF lung disease</b>http://ow.ly/iSQf30nAxxl
Potentialities of liquid biopsy in advanced non-small cell lung cancer (aNSCLC): Early evaluation of sentinel mutations in plasma and outcome of patients treated with immunotherapy
Authors: L. Bonanno, E. Zulato, I. Attili, A. Pavan, P. Del Bianco, G. Nardo, A. Boscolo Bragadin, L. Pasqualini, F. Calabrese, M. Fassan, G. Pasello, V. Guarneri, A. Amadori, P. Conte, S. Indraccolo
Journal: Annals of Oncology (2019)

Background: The introduction of immune-checkpoint inhibitors (ICIs) in the management of aNSCLC has led to great outcome improvement, but reliable predictive biomarkers are still a need. Liquid biopsy has the potential to monitor biological effects of treatment. Aim of the study is to explore the potential predictive value of its dynamic analysis in aNSCLC treated with ICIs. Methods: aNSCLC patients consecutively treated with ICIs at Istituto Oncologico Veneto were prospectively enrolled and genotyped in tissue. Plasma samples were collected at baseline (T1), after three or four weeks according to the administration schedule (T2) and at the moment of the first radiological evaluation (T3). Patients carrying KRAS mutation in tissue were analyzed in plasma with droplet digital PCR (ddPCR). Semiquantitative index of fractional abundancy of mutated allele (MAFA) was used. Results: aNSCLC patients (N: 54) were prospectively enrolled and tissue genotyped, 24 of them carried KRAS mutation in tissue and 11 (46%) were positive in plasma at baseline. Positivity was not associated with tumor burden or other clinical features. We evaluated the impact of the presence and the quantitative variation of MAFA during treatment on outcome in terms of progression free-survival (PFS). After a median follow-up of 10.9 months, the presence of sentinel mutation at T1 did not affect PFS, whereas the MAFA increase from baseline to T2 and to T3 were associated with shorter PFS (HR: 5.9, 95%CI: 1.2-27.7, p:0.02 and HR: 12.1, 95%CI: 2.3-23.8, p:0.003, respectively). Median PFS was 5.2 months in the presence of MAFA increase T1-2, while it was not reached in case of decreased/stable MAFA. Conclusions: Increase in MAFA from baseline to three or four weeks after the start of ICI is associated with shorter PFS. Predictive value of dynamic analysis of sentinel mutations in plasma during ICIs treatment warrants further validation in aNSCLC. Legal entity responsible for the study: Istituto Oncologico Veneto. Funding: Istituto Oncologico Veneto. Disclosure: All authors have declared no conflicts of interest.
Impact of pre-treatment absolute lymphocyte count, absolute monocyte count and their ratio on survival in diffuse large B cell lymphoma.
Authors: Ayham Deeb, Mahender Yellu, Tahir Latif, Gunjan Guha, Arun Sendilnathan, Abhimanyu Ghose, Stephen Charles Medlin
Journal: Journal of Clinical Oncology (2015)

e19521 Impact of pre-treatment absolute lymphocyte count, absolute monocyte count and their ratio on survival in diffuse large B cell lymphoma Background: Although the survival in diffuse large B cell lymphoma (DLBCL) has improved recently with the introduction of rituximab, a subset of patients still have worse outcome. Pre-treatment absolute lymphocyte count (ALC), absolute monocyte count (AMC) and their ratio (ALC/AMC) were found to predict the survival in different cancers but in DLBCL conflicting reports have been published. Also comprehensive evaluation of these pretreatment markers in predicting the survival in DLBCL is lacking.Methods: We retrospectively identified all the eligible DLBCL patients at our institute between January 2004 and October 2014. Patients who were treated with rituximab based chemotherapy are considered eligible for the study. Patients with incomplete pretreatment ALC and AMC data were excluded. Patients were classified into various groups based on their pre-treatment ALC and AMC numbers separately. Later the ratio was calculated for each individual patient. Primary end point is to study the significance of these markers in predicting the survival in DLBCL patients.Results: 142 consecutive patients with DLBCL were included in our study. 122 patients were considered eligible after applying the above described criteria. Patients were classified into four groups, with pretreatment ALC falling between 0-500, 501-1500, 1501-2500 and 2501-3500. The percent mortality associated for these groups is 45.46%, 19.05%, 18.18% and 12.51% respectively (P < 0.05). However, no statistically significant trend in mortality was observed with increased AMC. When the ratio of pre-treatmentALC to AMC was calculated, significant (P < 0.001) mortality trend was noted. For ALC/AMC between 0.1-4, the mortality rate was 14.77% and for ALC/AMC > 4, the mortality was 3.41%.Conclusions: Our study evaluated the usefulness of pre-treatment lymphocyte and monocyte level as the predictor for survival in DLBCL patients treated with rituximab based chemotherapy. Statistically, the ALC/AMC ratio was more significant than the ALC alone.
Tumor-associated Macrophages as Prognostic and Predictive Biomarkers for Postoperative Adjuvant Chemotherapy in Patients with Stage II Colon Cancer
Authors: Qingyang Feng, Wenju Chang, Yihao Mao, Guodong He, Peng Zheng, Wentao Tang, Ye Wei, Li Ren, Dexiang Zhu, Meiling Ji, Yongjiu Tu, Xinyu Qin, Jianmin Xu
Journal: Clinical Cancer Research (2019)

For stage II colon cancer, the efficacy of postoperative adjuvant chemotherapy remains controversial. It is well known that tumor-associated macrophages (TAMs) are important in tumor progression. In this study, TAMs were investigated as prognostic and predictive biomarkers for the efficacy of adjuvant chemotherapy for stage II colon cancer after radical resection.This study enrolled two independent cohorts of consecutive patients from one medical center with pathologic stage II colon cancer after radical resections. Macrophages were detected using IHC staining of CD68 and CD206. Infiltration densities of CD68+ TAMs, CD206+ TAMs, and ratio of CD206+ TAMs/CD68+ TAMs (CD206/CD68 ratio) were calculated as prognostic and predictive biomarkers.The primary and validation cohorts consisted of 521 and 314 patients, respectively. In both cohorts, high CD206/CD68 ratio was significantly associated with poor disease-free survival (DFS) and overall survival (OS). As an independent risk factor, CD206/CD68 ratio also had significantly better prognostic efficacy than CD68+ TAM density, CD206+ TAM density, and traditional clinicopathologic high-risk factors. Moreover, adjuvant chemotherapy significantly improved DFS and OS for patients with high CD206/CD68 ratio but not for those with low CD206/CD68 ratio. The interaction analyses were also significant for DFS. In subgroup analysis, CD206/CD68 ratio was still a significant predictor for adjuvant chemotherapy for patients in traditional high-risk group of recurrence (significant interaction for DFS).For stage II colon cancer, CD206/CD68 ratio is a better prognostic and predictive biomarker for postoperative adjuvant chemotherapy. Together with clinicopathologic high-risk factors, it will aid in precision treatment.