tbuckley/cabot-search huggingface dataset:
555P Metronomic oral vinorelbine (MOV) combined with tremelimumab (T) + durvalumab (D) in advanced solid tumours (AST): Dose finding results
Authors: A. Gonçalves, T. de La Motte Rouge, A. Bruno, N. Isambert, A. Hervieu, F. Legrand, C. Cropet
Journal: Annals of Oncology (2020)
1611P Healthcare resource utilization (HCRU) and costs in patients (pts) with advanced cancer treated with immune checkpoint inhibitors (ICIs) who experienced select immune-related adverse events (irAEs)
Authors: S. George, Y. Zheng, E.J. Bell, N.M. Engel-Nitz, J.C. White, L.S. Lal, R. Kim, S. Krulewicz, J. Smith, F.X. Liu
Journal: Annals of Oncology (2020)
Effects of Counseling by Peer Human Advisors vs Computers to Increase Walking in Underserved Populations
Authors: Abby C. King, Maria Ines Campero, Jylana L. Sheats, Cynthia M. Castro Sweet, Michelle E. Hauser, Dulce Garcia, Aldo Chazaro, German Blanco, Jorge Banda, David K. Ahn, Juan Fernandez, Timothy Bickmore
Journal: JAMA Internal Medicine (2020)

Effective and practical treatments are needed to increase physical activity among those at heightened risk from inactivity. Walking represents a popular physical activity that can produce a range of desirable health effects, particularly as people age.To test the hypothesis that counseling by a computer-based virtual advisor is no worse than (ie, noninferior to) counseling by trained human advisors for increasing 12-month walking levels among inactive adults.A cluster-randomized, noninferiority parallel trial enrolled 245 adults between July 21, 2014, and July 29, 2016, with follow-up through September 15, 2017. Data analysis was performed from March 15 to December 20, 2018. The evidence-derived noninferiority margin was 30 minutes of walking per week. Participants included inactive adults aged 50 years and older, primarily of Latin American descent and capable of walking without significant limitations, from 10 community centers in Santa Clara and San Mateo counties, California.All participants received similar evidence-based, 12-month physical activity counseling at their local community center, with the 10 centers randomized to a computerized virtual advisor program (virtual) or a previously validated peer advisor program (human).The primary outcome was change in walking minutes per week over 12 months using validated interview assessment corroborated with accelerometry. Both per-protocol and intention-to-treat analysis was performed.Among the 245 participants randomized, 193 were women (78.8%) and 241 participants (98.4%) were Latino. Mean (SD) age was 62.3 (8.4) years (range, 50-87 years), 107 individuals (43.7%) had high school or less educational level, mean BMI was 32.8 (6.8), and mean years residence in the US was 47.4 (17.0) years. A total of 231 participants (94.3%) completed the study. Mean 12-month change in walking was 153.9 min/wk (95% CI, 126.3 min/wk to infinity) for the virtual cohort (n = 123) and 131.9 min/wk (95% CI, 101.4 min/wk to infinity) for the human cohort (n = 122) (difference, 22.0, with lower limit of 1-sided 95% CI, -20.6 to infinity; P = .02); this finding supports noninferiority. Improvements emerged in both arms for relevant clinical risk factors, sedentary behavior, and well-being measures.The findings of this study indicate that a virtual advisor using evidence-based strategies produces significant 12-month walking increases for older, lower-income Latino adults that are no worse than the significant improvements achieved by human advisors. Changes produced by both programs are commensurate with those reported in previous investigations of these behavioral interventions and provide support for broadening the range of light-touch physical activity programs that can be offered to a diverse population.ClinicalTrials.gov Identifier: NCT02111213.
1965P Detection of BRCA1/2 mutations using next-generation sequencing in Asian patients with solid tumours
Authors: K.T. Tan, H-Y. Lu, Y-H. Jan, Y-L. Hsieh, D-W. Zhuo, J-L. Wu, W. Hsiao, K-P. Tse, C.T. Ng, S-J. Chen
Journal: Annals of Oncology (2020)
1635P Clinical and pathologic prognostic factors for residual lesion surgery following disease control with standard dose imatinib (IM) in patients (pts) with advanced gastrointestinal stromal tumor (GIST)
Authors: H. Cho, M.H. Ryu, S.M. Lee, Y. Park, Y.S. Park, H. Chae, K-H. Kim, C.W. Kim, B.S. Kim, M-W. Yoo, Y-K. Kang
Journal: Annals of Oncology (2020)
276O Pooled analysis of patient (pt)-reported quality of life (QOL) in the MONALEESA (ML)-2, -3, and -7 trials of ribociclib (RIB) plus endocrine therapy (ET) to treat hormone receptor–positive, HER2-negative (HR+/HER2−) advanced breast cancer (ABC)
Authors: P.A. Fasching, A. Bardia, A. Nusch, G. Jerusalem, A. Chan, N. El Saghir, E. Alba, S-A. Im, W. Janni, D. Chandiwana, B. Lanoue, A. Thuerigen, A. Gaur, N. Harbeck
Journal: Annals of Oncology (2020)
1236MO A single-arm phase II study of gefitinib with concurrent thoracic radiotherapy in unresectable locally-advanced non-small cell lung cancer patients with EGFR mutation (West Japan Oncology Group 6911L)
Authors: J. Shimizu, H. Akamatsu, H. Murakami, H. Harada, H. Hayashi, H. Daga, Y. Hasegawa, Y.H. Kim, T. Kato, S. Tokunaga, Y. Nishimura, N. Yamamoto, K. Nakagawa
Journal: Annals of Oncology (2020)
415P Prognostic effect of postoperative serum carcinoembryonic antigen (CEA) combined with T4 versus T3 tumors in patients with high-risk stage 2 colon cancer: ACHIEVE-2 phase III randomized clinical trial
Authors: A. Shiomi, M. Shiozawa, D. Manaka, M. Kotaka, Y. Sakamoto, A. Makiyama, Y. Munemoto, T. Rikiyama, M. Fukunaga, T. Ueki, K. Shitara, H. Shinkai, N. Tanida, E. Oki, T. Yamanaka, E. Sunami, K. Yamazaki, A. Ohtsu, Y. Maehara, T. Yoshino
Journal: Annals of Oncology (2020)
1277P An exosomal miRNA signature as predictor of benefit from immune checkpoint inhibitors in non-small cell lung cancer
Authors: C. Genova, S. Coco, G. Rossi, L. Longo, G. Chiorino, P. Ostano, F. Guana, G. Metro, S. Baglivo, V. Ludovini, I. Vanni, E. Rijavec, F. Biello, M.G. Dal Bello, M. Tagliamento, C. Dellepiane, A. Alama, E. Bennicelli, R. Chiari, F. Grossi
Journal: Annals of Oncology (2020)
432P Toxicity and efficacy of 1st line cetuximab (cetux)-based therapy in RAS wildtype (WT) older patients (pts) with metastatic colorectal cancer (mCRC): A pooled analysis from 1,274 pts in the ARCAD database
Authors: D. Papamichael, G.S. Lopes, C.L. Olswold, B. Chibaudel, J.R. Zalcberg, E. Van Cutsem, A. Venook, T. Maughan, V. Heinemann, R.S. Kaplan, C. Bokemeyer, H.J. Lenz, T. Yoshino, R.A. Adams, A. Grothey, A. De Gramont, Q. Shi
Journal: Annals of Oncology (2020)
Store-Operated Ca<sup>2+</sup> Channels: Mechanism, Function, Pharmacology, and Therapeutic Targets
Authors: Daniel Bakowski, Fraser Murray, Anant B. Parekh
Journal: The Annual Review of Pharmacology and Toxicology (2020)

Calcium (Ca2+) release-activated Ca2+ (CRAC) channels are a major route for Ca2+ entry in eukaryotic cells. These channels are store operated, opening when the endoplasmic reticulum (ER) is depleted of Ca2+, and are composed of the ER Ca2+ sensor protein STIM and the pore-forming plasma membrane subunit Orai. Recent years have heralded major strides in our understanding of the structure, gating, and function of the channels. Loss-of-function and gain-of-function mutants combined with RNAi knockdown strategies have revealed important roles for the channel in numerous human diseases, making the channel a clinically relevant target. Drugs targeting the channels generally lack specificity or exhibit poor efficacy in animal models. However, the landscape is changing, and CRAC channel blockers are now entering clinical trials. Here, we describe the key molecular and biological features of CRAC channels, consider various diseases associated with aberrant channel activity, and discuss targeting of the channels from a therapeutic perspective.
Microfabrication: Tailoring Common Hydrogels into 3D Cell Culture Templates (Adv. Healthcare Mater. 18/2020)
Authors: Aurélien Pasturel, Pierre‐Olivier Strale, Vincent Studer
Journal: Advanced Healthcare Materials (2020)

The toolbox presented in article number 2000519 by Vincent Studer and co-workers provides natural hydrogel prototyping operations that are queued. With a commercialy available patterned UV light projection system, flat layers of commonplace hydrogels can be shaped and then decorated with adhesion proteins. Cells seeded on these hydrogel templates self-organize into 3D cellular models.
The BMJ interview: Anthony Fauci on covid-19
Authors: Fiona Godlee, Joanne Silberner
Journal: BMJ (2020)

There are few better known authorities on the covid-19 pandemic than Anthony Fauci.One of the world's most respected infectious disease experts, he spoke with The BMJ's editor, Fiona Godlee, about the pressures of advising the US president, the challenging nature of the new coronavirus, and how the pandemic might end.He's become a familiar face and voice in America: on television, radio, podcasts, YouTube videos, and congressional hearings, talking through the intricacies of covid-19 in a calm Brooklyn accent, with everyone from JAMA to Julia Roberts.Fauci was at President Trump's side when the US declared a national state of emergency in March and remains a member of the White House Coronavirus Task Force, even as his dedication to communication and evidence based science has at times put him at odds with the administration.
Automated Recognition of Regional Wall Motion Abnormalities Through Deep Neural Network Interpretation of Transthoracic Echocardiography
Authors: Mu-Shiang Huang, Chi-Shiang Wang, Jung-Hsien Chiang, Ping-Yen Liu, Wei-Chuan Tsai
Journal: Circulation (2020)

Automated interpretation of echocardiography by deep neural networks could support clinical reporting and improve efficiency. Whereas previous studies have evaluated spatial relationships using still frame images, we aimed to train and test a deep neural network for video analysis by combining spatial and temporal information, to automate the recognition of left ventricular regional wall motion abnormalities.We collected a series of transthoracic echocardiography examinations performed between July 2017 and April 2018 in 2 tertiary care hospitals. Regional wall abnormalities were defined by experienced physiologists and confirmed by trained cardiologists. First, we developed a 3-dimensional convolutional neural network model for view selection ensuring stringent image quality control. Second, a U-net model segmented images to annotate the location of each left ventricular wall. Third, a final 3-dimensional convolutional neural network model evaluated echocardiographic videos from 4 standard views, before and after segmentation, and calculated a wall motion abnormality confidence level (0-1) for each segment. To evaluate model stability, we performed 5-fold cross-validation and external validation.In a series of 10 638 echocardiograms, our view selection model identified 6454 (61%) examinations with sufficient image quality in all standard views. In this training set, 2740 frames were annotated to develop the segmentation model, which achieved a Dice similarity coefficient of 0.756. External validation was performed in 1756 examinations from an independent hospital. A regional wall motion abnormality was observed in 8.9% and 4.9% in the training and external validation datasets, respectively. The final model recognized regional wall motion abnormalities in the cross-validation and external validation datasets with an area under the receiver operating characteristic curve of 0.912 (95% CI, 0.896-0.928) and 0.891 (95% CI, 0.834-0.948), respectively. In the external validation dataset, the sensitivity was 81.8% (95% CI, 73.8%-88.2%), and specificity was 81.6% (95% CI, 80.4%-82.8%).In echocardiographic examinations of sufficient image quality, it is feasible for deep neural networks to automate the recognition of regional wall motion abnormalities using temporal and spatial information from moving images. Further investigation is required to optimize model performance and evaluate clinical applications.
329P Ribociclib (RIB) in patients (pts) with HR+/HER2− advanced breast cancer (ABC) and resistance to prior endocrine therapy (ET) in the MONALEESA (ML) -3 and -7 trials
Authors: S.A. Hurvitz, S.C. Lee, G. Jerusalem, S-A. Im, S.K.L. Chia, S. Campos, G.S. Sonke, A. Lteif, H. Hu, Y. Wang, K. Rodriguez-Lorenc, Y-S. Lu
Journal: Annals of Oncology (2020)
Advanced endoscopic imaging of colonic schistosomiasis
Authors: Alanna Ebigbo, Maria Kahn, Stephan Zellmer, Helmut Messmann
Journal: Endoscopy (2020)

A 21-year-old patient was referred to our unit with a 3-month history of abdominal discomfort, bloating, and intermittent diarrhea. Physical findings were normal; however, eosinophilia (4300/µL; 35 %) was detected. Stool analysis for ova and parasites was negative. Subsequent endoscopy with extended depth of field as well as texture and color enhancement imaging (TXI) (Olympus EVIS X1 CV 1500) showed small whitish subepithelial nodules in all segments of the colon, which were especially visible in TXI mode ([Fig. 1]; [Video 1]). In addition, some nodules had a central dark spot which was clearly visible as a protruding nipple on magnified narrow-band imaging (NBI) ([Fig. 2]; [Video 1]). Histopathological analysis of snare resection specimens showed multiple eosinophilic granulomas with Schistosoma mansoni eggs in the lamina propria [1]. The dark “nipple” seen on endoscopy was interpreted as a granuloma on the verge of bursting and releasing parasite eggs into the intestinal lumen. Endoscopic imaging of egg release of this clarity and detail in intestinal schistosomiasis has not been published before.
850P Genetic factors contributing to the success rate of patient-derived xenograft revealed by genomic characterization in epithelial ovarian cancer
Authors: Y. Shan, X. Peng, S. Li, L. Pan, J. Ying, C. Qiao, S. Peng, X. Guo, H. Li, W. Wang, Y. Li, Y. Gu
Journal: Annals of Oncology (2020)
Lessons from tofacitinib in patients with cardiovascular risk factors: increased pulmonary embolism or isolated (thrombotic) pulmonary occlusion rates?
Authors: Thomas Dörner
Journal: Annals of the Rheumatic Diseases (2020)

Figure 1 Triad of VTE risk assessment requires consideration of individual patient factors, underlying disease (including potential disease activity) and risks related to medication/treatment.With regard to patient risks, the study by Mease et al 5 reports that elevated cardiovascular (ATE) risks may contribute disproportionally to increased PE rates under 10 mg tofacitinib dose.This might indicate a potential segregation from conventional thrombophilic factors.DVT, deep vein thrombosis; PE, pulmonary embolism; VTE, venous thromboembolic event.
1642P Treatment results of patients diagnosed with rare types of bone sarcomas
Authors: H.M. Kosela Paterczyk, A. Mariuk-Jarema, P. Teterycz, T. Switaj, K. Kozak, P. Jagodzinska-Mucha, A. Klimczak, P. Rogala, M. Wagrodzki, S. Falkowski, P. Rutkowski
Journal: Annals of Oncology (2020)
567P Exposure-response analyses of dabrafenib and trametinib in melanoma patients
Authors: S.L. Groenland, J.M. Janssen, C. Nijenhuis, N. de Vries, H. Rosing, S. Wilgenhof, J.V. van Thienen, J.B.A.G. Haanen, C.U. Blank, J. Beijnen, A. Huitema, N. Steeghs
Journal: Annals of Oncology (2020)
1850P Immune-related endocrine dysfunction in Chinese: A single tertiary centre experience
Authors: W.W.L. Chan, P. Ho, O. Leung, K.S. Lau, J. Au, V. Lam, I. Ho, B. Cheung, E. Lam, C. Wong, R. Liu, R. Tse, D. Chow, T. Tse, K.O. Lam, V.H.F. Lee, H.C.W. Choi
Journal: Annals of Oncology (2020)
LBA69 Impact of the COVID-19 pandemic on management of medical cancer treatments and psychological consequence for the patients
Authors: F. Joly, A. Leconte, J-M. Grellard, J. Lequesne, G. Binarelli, M. Lange, L. Tron, F. Gernier, C. Rieux, M. Fernette, E. Bastien, A. Morel, B. Legrand, D. Richard, A. Faveyrial, R. Travers, L-F. Pépin, O. Rigal, F. Jardin, B. Clarisse
Journal: Annals of Oncology (2020)
890MO Phase I Alexander study of AUTO3, the first CD19/22 dual targeting CAR.T cell, with pembrolizumab in patients with relapsed/refractory (r/r) DLBCL
Authors: E. Tholouli, W. Osborne, C. Bachier, A. Ramakrishnan, M. Marzolini, D. Irvine, P. McSweeney, N. Bartlet, Y. Zhang, S. Thomas, M. Al-Hajj, M. Pule, M. Jonnaert, V. Peddareddigari, N. Khokhar, R. Chen, K. Ardesha
Journal: Annals of Oncology (2020)
304P ESR1 mutations and outcomes in BRCA1/2 or PALB2 germline mutation carriers receiving first line aromatase inhibitor + palbociclib (AI+P) for metastatic breast cancer (MBC) in the PADA-1 trial
Authors: J-S. Frenel, F. Dalenc, B. Pistilli, T. de La Motte Rouge, C. Levy, M-A. Mouret-Reynier, A-C. Hardy-Bessard, N. Bonichon-Lamichhane, C. Greilsamer, V. Delecroix, S. Nguyen, F. Berger, S. Everhard, J. Lemonnier, D. Loirat, C. Callens, A. Pradines, T. Bachelot, S. Delaloge, F.C. Bidard
Journal: Annals of Oncology (2020)
1530P Gemcitabine/nab-paclitaxel versus (modified) FOLFIRINOX for palliative first-line treatment of advanced pancreatic cancer: A propensity score analysis
Authors: J.M. Riedl, F. Posch, L. Horvath, A. Gantschnigg, F. Renneberg, E. Schwarzenbacher, F. Moik, D. Barth, M. Stotz, R. Schaberl-Moser, M. Pichler, H. Stöger, R. Greil, A. Djanani, K. Schlick, A. Gerger
Journal: Annals of Oncology (2020)
Evaluation of Daratumumab for the Treatment of Multiple Myeloma in Patients With High-risk Cytogenetic Factors
Authors: Smith Giri, Alyssa Grimshaw, Susan Bal, Kelly Godby, Prakash Kharel, Benjamin Djulbegovic, Meletios A. Dimopoulos, Thierry Facon, Saad Z. Usmani, María-Victoria Mateos, Luciano J. Costa
Journal: JAMA Oncology (2020)

The addition of daratumumab to backbone multiple myeloma (MM) regimens is associated with improved response rates and progression-free survival (PFS). Whether improved outcomes are also associated with this regimen among patients with cytogenetically defined high-risk MM (HRMM) remains unclear.To measure PFS associated with adding daratumumab to backbone MM regimens among patients with HRMM.For this systematic review and meta-analysis, MEDLINE, Embase, PubMed, Scopus, Web of Science Core Collection, Cochrane Library, clinical trials registries, and meeting libraries were searched from inception to January 2, 2020, using terms reflecting multiple myeloma and daratumumab.Included studies were phase 3 randomized clinical trials that compared backbone MM regimens with the same regimen plus daratumumab in newly diagnosed or relapsed or refractory MM, such that the only difference between the intervention and control groups was use of daratumumab and reported outcomes by cytogenetic risk. High-risk MM was defined as the presence of t(4;14), t(14;16), or del(17p).Using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline, 2 investigators independently extracted study data, with disagreements resolved by a third investigator. Quality was assessed by the Cochrane risk-of-bias method.Data on effectiveness were extracted using hazard ratios (HRs) for PFS. Relative log-HRs were pooled using a DerSimonian-Laird random-effects model. Heterogeneity was assessed using the Cochran Q and the I2 statistic.Of 5194 studies screened, 6 phase 3 trials were eligible, including 3 trials for newly diagnosed MM (2528 patients; 358 with HRMM) and 3 trials for relapsed or refractory MM (1533 patients; 222 with HRMM). Among patients with newly diagnosed HRMM, the addition of daratumumab to backbone regimens was associated with improved PFS (pooled HR, 0.67; 95% CI, 0.47-0.95; P = .02), with little evidence of heterogeneity (Cochran Q, P = .77; I2 = 0%). Similar results were seen among patients with relapsed or refractory HRMM (pooled HR, 0.45; 95% CI, 0.30-0.67; P < .001), again with little evidence of heterogeneity (Cochran Q, P = .63; I2 = 0%).This study suggests that incorporating daratumumab to backbone regimens may be associated with improved PFS among patients with newly diagnosed HRMM or relapsed or refractory HRMM.
NOTCH-induced rerouting of endosomal trafficking disables regulatory T cells in vasculitis
Authors: Ke Jin, Zhenke Wen, Bowen Wu, Hui Zhang, Jingtao Qiu, Yanan Wang, Kenneth J. Warrington, Gerald J. Berry, Jorg J. Goronzy, Cornelia M. Weyand
Journal: Journal of Clinical Investigation (2020)

The aorta and the large conductive arteries are immunoprivileged tissues and are protected against inflammatory attack. A breakdown of immunoprivilege leads to autoimmune vasculitis, such as giant cell arteritis, in which CD8+ Treg cells fail to contain CD4+ T cells and macrophages, resulting in the formation of tissue-destructive granulomatous lesions. Here, we report that the molecular defect of malfunctioning CD8+ Treg cells lies in aberrant NOTCH4 signaling that deviates endosomal trafficking and minimizes exosome production. By transcriptionally controlling the profile of RAB GTPases, NOTCH4 signaling restricted vesicular secretion of the enzyme NADPH oxidase 2 (NOX2). Specifically, NOTCH4hiCD8+ Treg cells increased RAB5A and RAB11A expression and suppressed RAB7A, culminating in the accumulation of early and recycling endosomes and sequestering of NOX2 in an intracellular compartment. RAB7AloCD8+ Treg cells failed in the surface translocation and exosomal release of NOX2. NOTCH4hiRAB5AhiRAB7AloRAB11AhiCD8+ Treg cells left adaptive immunity unopposed, enabling a breakdown in tissue tolerance and aggressive vessel wall inflammation. Inhibiting NOTCH4 signaling corrected the defect and protected arteries from inflammatory insult. This study implicates NOTCH4-dependent transcriptional control of RAB proteins and intracellular vesicle trafficking in autoimmune disease and in vascular inflammation.
1387P Phase Ib study of LXH254 + LTT462 in patients with KRAS- or BRAF-mutant NSCLC
Authors: J. Wolf, D. Planchard, R.S. Heist, B. Solomon, M. Sebastian, A. Santoro, N. Reguart, U. Stammberger, L. Manganelli, H. Wu, A. Mais, C. Dooms
Journal: Annals of Oncology (2020)
58P Quality of life (QoL) outcomes with futibatinib treatment in FOENIX-CCA2 - A phase II study in patients (pts) with intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 gene fusions/rearrangements
Authors: J.W. Valle, A. Hollebecque, J. Furuse, L. Goyal, F. Meric-Bernstam, R. Morlock, Y. He, K. Benhadji, J. Bridgewater
Journal: Annals of Oncology (2020)
Extracellular vesicles in hepatology: Physiological role, involvement in pathogenesis, and therapeutic opportunities
Authors: Maria Azparren-Angulo, Felix Royo, Esperanza Gonzalez, Marc Liebana, Bruno Brotons, Jesús Berganza, Felipe Goñi-de-Cerio, Nicoló Manicardi, Laia Abad-Jordà, Jordi Gracia-Sancho, Juan M. Falcon-Perez
Journal: Pharmacology & Therapeutics (2020)

Since the first descriptions of hepatocyte-released exosome-like vesicles in 2008, the number of publications describing Extracellular Vesicles (EVs) released by liver cells in the context of hepatic physiology and pathology has grown exponentially. This growing interest highlights both the importance that cell-to-cell communication has in the organization of multicellular organisms from a physiological point of view, as well as the opportunity that these circulating organelles offer in diagnostics and therapeutics. In the present review, we summarize systematically and comprehensively the myriad of works that appeared in the last decade and lighted the discussion about the best opportunities for using EVs in liver disease therapeutics.