tbuckley/cabot-search huggingface dataset:
Chromosome-Scale Genome Assemblies of Aphids Reveal Extensively Rearranged Autosomes and Long-Term Conservation of the X Chromosome
Authors: Thomas C Mathers, Roland H M Wouters, Sam T Mugford, David Swarbreck, Cock van Oosterhout, Saskia A Hogenhout
Journal: Molecular Biology and Evolution (2020)

Abstract Chromosome rearrangements are arguably the most dramatic type of mutations, often leading to rapid evolution and speciation. However, chromosome dynamics have only been studied at the sequence level in a small number of model systems. In insects, Diptera and Lepidoptera have conserved genome structure at the scale of whole chromosomes or chromosome arms. Whether this reflects the diversity of insect genome evolution is questionable given that many species exhibit rapid karyotype evolution. Here, we investigate chromosome evolution in aphids—an important group of hemipteran plant pests—using newly generated chromosome-scale genome assemblies of the green peach aphid (Myzus persicae) and the pea aphid (Acyrthosiphon pisum), and a previously published assembly of the corn-leaf aphid (Rhopalosiphum maidis). We find that aphid autosomes have undergone dramatic reorganization over the last 30 My, to the extent that chromosome homology cannot be determined between aphids from the tribes Macrosiphini (Myzus persicae and Acyrthosiphon pisum) and Aphidini (Rhopalosiphum maidis). In contrast, gene content of the aphid sex (X) chromosome remained unchanged despite rapid sequence evolution, low gene expression, and high transposable element load. To test whether rapid evolution of genome structure is a hallmark of Hemiptera, we compared our aphid assemblies with chromosome-scale assemblies of two blood-feeding Hemiptera (Rhodnius prolixus and Triatoma rubrofasciata). Despite being more diverged, the blood-feeding hemipterans have conserved synteny. The exceptional rate of structural evolution of aphid autosomes renders them an important emerging model system for studying the role of large-scale genome rearrangements in evolution.
Correction to: CD103-positive CSC exosome promotes EMT of clear cell renal cell carcinoma: role of remote MiR-19b-3p
Authors: Lu Wang, Guang Yang, Danfeng Zhao, Jiaqi Wang, Yang Bai, Qiang Peng, Hongzhi Wang, Ruizhe Fang, Guang Chen, Zhichao Wang, Keliang Wang, Guangbin Li, Yinhui Yang, Ziqi Wang, Pengyu Guo, Li Peng, Dayong Hou, Wanhai Xu
Journal: Molecular Cancer (2020)

An amendment to this paper has been published and can be accessed via the original article.
1507P A retrospective study of angiotensin-converting enzyme inhibitors or beta-blockers to prevent trastuzumab-induced cardiotoxicity
Authors: K. Sun, K. Anand, S. Manne, X. Xu, M. Niravath, J.C. Nicolas, S.L. Jones, T.A. Patel, C. Geyer, J.C. Chang, P. Niravath
Journal: Annals of Oncology (2020)
Targeting gut microbiota for precision medicine: Focusing on the efficacy and toxicity of drugs
Authors: Wuwen Feng, Juan Liu, Hui Ao, Shijun Yue, Cheng Peng
Journal: Theranostics (2020)

Intra- and interindividual variation in drug responses is one major reason for the failure of drug therapy, drug toxicity, and even the death of patients. Precision medicine, or personalized medicine, is a field of medicine that customizes an individual's medical diagnosis and treatment based on his/her genes, microbiomes, environments, etc. Over the past decade, a large number of studies have demonstrated that gut microbiota can modify the efficacy and toxicity of drugs, and the extent of the modification varies greatly from person to person because of the variability of the gut microbiota. Personalized manipulation of gut microbiota is an important approach to rectify the abnormal drug response. In this review, we aim to improve drug efficacy and reduce drug toxicity by combining precision medicine and gut microbiota. After describing the interactions between gut microbiota and xenobiotics, we discuss (1) the effects of gut microbiota on drug efficacy and toxicity and the corresponding mechanisms, (2) the variability of gut microbiota, which leads to variation in drug responses, (3) the biomarkers used for the patient stratification and treatment decisions before the use of drugs, and (4) the methods used for the personalized manipulation of gut microbiota to improve drug outcomes. Overall, we hope to improve the drug response by incorporating the knowledge of gut microbiota into clinical practice.
605TiP Targeting anti-cancer drug resistance in gastro-intestinal cancer: Inhibition of the SRPK1 kinase and degradation of the ABCG2 drug efflux pump
Authors: M. Ladekarl, J.H.V. Schou, N.L. Roest, J. Stenvang, N. Brünner, P.M. Vestlev
Journal: Annals of Oncology (2020)
1568O Quality of life in cancer patients treated with immune checkpoint inhibitors: A meta-analysis
Authors: B.D. Gonzalez, S.L. Eisel, K.E. Bowles, A.I. Hoogland, B.W. James, B.J. Small, S. Sharpe, K.A. Hyland, H.W. Bulls, S.M. Christy, J. Mansfield, A.M. Nelson, R. Alla, K. Maharaj, B. Kennedy, E. Lafranchise, N.L. Williams, M.A. Postow, A.P. Dicker, H.S.L. Jim
Journal: Annals of Oncology (2020)
336P PI3K pathway biomarkers and clinical response in a phase I/Ib study of GDC-0077 in hormone receptor-positive/HER2-negative breast cancer (HR+/HER2– BC)
Authors: V. Gambardella, A. Cervantes, P.L. Bedard, E.P. Hamilton, A. Italiano, K. Jhaveri, D. Juric, K. Kalinsky, I.E. Krop, M. Oliveira, C. Saura, P. Schmid, N. Turner, A. Varga, B.P. Liu, J.W. Chen, J. Aimi, S. Royer-Joo, J.L. Schutzman, K.E. Hutchinson
Journal: Annals of Oncology (2020)
Targeting HIF2α-ARNT hetero-dimerisation as a novel therapeutic strategy for pulmonary arterial hypertension
Authors: David Macias, Stephen Moore, Alexi Crosby, Mark Southwood, Xinlin Du, Huiling Tan, Shanhai Xie, Arlette Vassallo, Alexander J.T. Wood, Eli M. Wallace, Andrew S. Cowburn
Journal: European Respiratory Journal (2020)

Pulmonary arterial hypertension (PAH) is a destructive disease of the pulmonary vasculature often leading to right heart failure and death. Current therapeutic intervention strategies only slow disease progression. The role of aberrant hypoxia-inducible factor (HIF)2α stability and function in the initiation and development of pulmonary hypertension (PH) has been an area of intense interest for nearly two decades. Here we determine the effect of a novel HIF2α inhibitor (PT2567) on PH disease initiation and progression, using two pre-clinical models of PH. Haemodynamic measurements were performed, followed by collection of heart, lung and blood for pathological, gene expression and biochemical analysis. Blood outgrowth endothelial cells from idiopathic PAH patients were used to determine the impact of HIF2α-inhibition on endothelial function. Global inhibition of HIF2a reduced pulmonary vascular haemodynamics and pulmonary vascular remodelling in both su5416/hypoxia prevention and intervention models. PT2567 intervention reduced the expression of PH-associated target genes in both lung and cardiac tissues and restored plasma nitrite concentration. Treatment of monocrotaline-exposed rodents with PT2567 reduced the impact on cardiovascular haemodynamics and promoted a survival advantage. In vitro , loss of HIF2α signalling in human pulmonary arterial endothelial cells suppresses target genes associated with inflammation, and PT2567 reduced the hyperproliferative phenotype and overactive arginase activity in blood outgrowth endothelial cells from idiopathic PAH patients. These data suggest that targeting HIF2α hetero-dimerisation with an orally bioavailable compound could offer a new therapeutic approach for PAH. Future studies are required to determine the role of HIF in the heterogeneous PAH population.
Combined immunodeficiency caused by a novel homozygous NFKB1 mutation
Authors: Amarilla B. Mandola, Nigel Sharfe, Zahra Nagdi, Harjit Dadi, Linda Vong, Daniele Merico, Bo Ngan, Brenda Reid, Chaim M. Roifman
Journal: Journal of Allergy and Clinical Immunology (2020)
521TiP Circulating tumor DNA guided adjuvant chemotherapy in stage II colon cancer according the trials within cohorts design: The MEDOCC-CrEATE trial
Authors: S. Schraa, K. Van Rooijen, D.V.D. Kruijssen, C. Rubio Alarcón, J. Phallen, M. Sausen, J. Simmons, V. Coupe, H. Van Grevenstein, S. Elias, H. Verkooijen, L. Bosch, D. Van Den Broek, G. Meijer, V. Velculescu, R. Fijneman, G. Vink, M. Koopman
Journal: Annals of Oncology (2020)
1621MO Long-term efficacy, tolerability and overall survival in patients (pts) with unresectable or metastatic (U/M) PDGFRA D842V-mutant gastrointestinal stromal tumour (GIST) treated with avapritinib: NAVIGATOR phase I trial update
Authors: R.L. Jones, C. Serrano, M. von Mehren, S. George, M. Heinrich, Y-K. Kang, P. Schoeffski, P. Cassier, O. Mir, S.P. Chawla, F.A. Eskens, P. Rutkowski, W.D. Tap, T. Zhou, M. Roche, S. Bauer
Journal: Annals of Oncology (2020)
876P The effect of surgical techniques on sexuality and global quality of life (Qol) in women with ovarian germ cell (OGCT) and sex cord stromal tumours (SCST): An analysis of the AGO-CORSETT database
Authors: A. Hasenburg, H. Plett, B. Krämer, E. Braicu, B. Czogalla, M. Bossart, S. Singer, D. Mayr, A. Staebler, A. du Bois, S. Kommoss, T. Link, A. Burges, F. Heitz, J. Keul, F. Trillsch, P. Harter, P. Wimberger, P. Buderath, M. Klar
Journal: Annals of Oncology (2020)
ReScan, a Multiplex Diagnostic Pipeline, Pans Human Sera for SARS-CoV-2 Antigens
Authors: Colin R. Zamecnik, Jayant V. Rajan, Kevin A. Yamauchi, Sabrina A. Mann, Rita P. Loudermilk, Gavin M. Sowa, Kelsey C. Zorn, Bonny D. Alvarenga, Christian Gaebler, Marina Caskey, Mars Stone, Philip J. Norris, Wei Gu, Charles Y. Chiu, Dianna Ng, James R. Byrnes, Xin X. Zhou, James A. Wells, Davide F. Robbiani, Michel C. Nussenzweig, Joseph L. DeRisi, Michael R. Wilson
Journal: Cell Reports Medicine (2020)

Comprehensive understanding of the serological response to SARS-CoV-2 infection is important for both pathophysiologic insight and diagnostic development. Here, we generate a pan-human coronavirus programmable phage display assay to perform proteome-wide profiling of coronavirus antigens enriched by 98 COVID-19 patient sera. Next, we use ReScan, a method to efficiently sequester phage expressing the most immunogenic peptides and print them onto paper-based microarrays using acoustic liquid handling, which isolates and identifies nine candidate antigens, eight of which are derived from the two proteins used for SARS-CoV-2 serologic assays: spike and nucleocapsid proteins. After deployment in a high-throughput assay amenable to clinical lab settings, these antigens show improved specificity over a whole protein panel. This proof-of-concept study demonstrates that ReScan will have broad applicability for other emerging infectious diseases or autoimmune diseases that lack a valid biomarker, enabling a seamless pipeline from antigen discovery to diagnostic using one recombinant protein source.
Covid 19: a fork in the road for general practice
Authors: Denis Pereira Gray, George Freeman, Catherine Johns, Martin Roland
Journal: BMJ (2020)

Covid-19 has produced the biggest change in the organisation of UK general practice for 200 years.As in many countries, face-to-face consultations have fallen to about 10% of their previous level and most contacts are now provided remotely using symptom checkers, electronic messaging, and phone or video consultations.Several of these changes may be permanent, with fewer face-to-face consultations in future.Opportunity and danger are two aspects of change: both now apply to general practice.GPs currently have quieter waiting rooms, fewer locums, and reduced regulatory burdens such as from Care Quality Commission inspections.However, normal workload is returning, and while remote consulting makes access much easier for some patients, there is a real risk that general practice will suddenly become less personal.Worryingly, remote consultations may increase overall GP workload and exclude patients without internet access.
1311P First-line (1L) nivolumab (NIVO) + ipilimumab (IPI) + chemotherapy (chemo) in Asian patients (pts) with advanced non-small cell lung cancer (NSCLC) from CheckMate 9LA
Authors: T. John, H. Sakai, S. Ikeda, Y. Cheng, K. Kasahara, Y. Sato, Y. Nakahara, M. Takeda, H. Kaneda, H. Zhang, M. Maemondo, K. Minato, T. Hisada, Y. Misumi, M. Satouchi, K. Hotta, A. Li, A. Oukessou, S. Lu
Journal: Annals of Oncology (2020)
717P Comparison of long-term survival and cost-effectiveness (CE) of first-line (1L) treatment options in advanced renal cell carcinoma (aRCC) with intermediate or poor (I/P) prognostic risk
Authors: T.K. Choueiri, B. Stwalley, S. Huo, J.R. May, B. Malcolm, K. Nickel, N. Szabo, S. Klijn
Journal: Annals of Oncology (2020)
1154TiP A randomized, prospective, multicenter study to assess the impact of early detection of asymptomatic brain metastases (mets) vs standard follow-up on symptomatic brain mets free survival (SBMFS) in pts with previously untreated, unresectable or metastatic melanoma (MM)
Authors: E. Munoz Couselo, C. Ortiz Velez, R. Dienstmann, G. Villacampa Javierre, M. Carboneras, S. Muñoz, M. Batista, M. Gonzalez, C. Auger, A. Rovira, F. Martinez-Ricarte
Journal: Annals of Oncology (2020)
243P UK experience of the management of pregnancy associated breast cancer: A national retrospective review of practice
Authors: E.F. Goode, D. Crawley, C. Moss, A. Okines, C. Archer, J. Gale, M. Zaidi, J.R. Howells, M. Khan, R.E. Board, P. Huddar, G. Eslamian, K. Herring, S. Lighttowers, H. McKenzie, S. Irshad
Journal: Annals of Oncology (2020)
Modelling t(8;21) acute myeloid leukaemia ‐ What have we learned?
Authors: Paulynn Suyin Chin, Constanze Bonifer
Journal: MedComm (2020)

Abstract Acute myeloid leukaemia (AML) is a heterogeneous haematopoietic malignancy caused by recurrent mutations in haematopoietic stem and progenitor cells that affect both the epigenetic regulatory machinery and signalling molecules. The t(8;21) or RUNX1‐RUNX1T1 translocation generates the RUNX1‐ETO chimeric transcription factor which primes haematopoietic stem cells for further oncogenic mutational events that in their sum cause overt disease. Significant progress has been made in generating both in vitro and in vivo model systems to recapitulate t(8;21) AML which are crucial for the understanding of the biology of the disease and the development of effective treatment. This review provides a comprehensive overview of the in vivo and in vitro model systems that were developed to gain insights into the molecular mechanisms of RUNX1‐ETO oncogenic activity and their contribution to the advancement of knowledge in the t(8;21) AML field. Such models include transgenic mice, patient‐derived xenografts, RUNX1‐ETO transduced human progenitor cells, cell lines and human embryonic stem cell model systems, making the t(8;21) as one of the well‐characterized sub‐type of AML at the molecular level.
Redox DAPK1 destabilizes Pellino1 to govern inflammation-coupling tubular damage during septic AKI
Authors: Bang-Chuan Hu, Guo-Hua Wu, Zi-Qiang Shao, Yang Zheng, Jin-Quan Liu, Run Zhang, Jun Hong, Xiang-Hong Yang, Ren-Hua Sun, Shi-Jing Mo
Journal: Theranostics (2020)

Tubular damage initiated by inflammatory response and ischemic/hypoxic stress is a hallmark of septic acute kidney injury (AKI), albeit the molecular mechanism coupling the two events remains unclear. We investigated the intrinsic nature of tubular damage with respect to inflammatory/hypoxic stress during septic AKI. Methods: The apoptotic response of tubular cells to LPS stimuli was analyzed before and after hypoxia exposure. Cellular ubiquitination, co-immunoprecipitation, GST-pulldown, in vitro protein kinase assay, immunofluorescence and CRISPR technology were adopted to determine the molecular mechanism underlying this process. In vivo characterization was performed in wild-type and DAPK1-/- mice models of cecal ligation and puncture (CLP). Results: We found that the MyD88-dependent inflammatory response couples to tubular damage during LPS stimuli under hypoxia in a Fn14/SCFFbxw7α-dispensable manner via recruitment of caspase-8 with TRIF-RIP1 signalosome mediated by DAPK1, which directly binds to and phosphorylates Pellino1 at Ser39, leading to Pellino1 poly-ubiquitination and turnover. Either pharmacological deactivation or genetic ablation of DAPK1 makes tubular cells refractory to the LPS-induced damage in the context of hypoxia, while kinase activity of DAPK1 is essential for ruin execution. Targeting DAPK1 effectively protects mice against septic AKI and potentiates the efficacy of a MyD88 homodimerization inhibitor, ST2825. Conclusion: Our findings provide a rationale for the mechanism whereby inflammation intersects with hypoxic tubular damage during septic AKI through a previously unappreciated role of DAPK1-inducible Ser39 phosphorylation in Pellino1 turnover and underscore that combined targeting DAPK1 and MyD88 might be a feasible strategy for septic AKI management.
Redefining Left Ventricular Assist Device Indications and Strategies
Authors: Muddassir Mehmood
Journal: JAMA Cardiology (2020)

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Avid 68Ga-PSMA Uptake in Periappendicular Abscess
Authors: Mads Tranberg Christensen, Søren Klingenberg, Lars Christian Gormsen, Mads Ryø Jochumsen, Kirsten Bouchelouche
Journal: Clinical Nuclear Medicine (2020)

Abstract 68 Ga–prostate-specific membrane antigen (PSMA) PET/CT for primary staging of high-risk prostate cancer revealed increased 68 Ga-PSMA uptake in a known periappendicular abscess in a patient, who had undergone surgical drainage of the abscess 1 month earlier. The case presents another example of 68 Ga-PSMA uptake in a benign infectious and inflammatory condition.
687TiP ARC-6: A phase Ib/II, open-label, randomized platform study evaluating the efficacy and safety of AB928-based treatment combinations in patients with metastatic castrate resistant prostate cancer
Authors: S.K. Subudhi, D. Wise, S.T. Liu, A. Chaudhry, J. Kim, O. Gardner, H. Gilbert, M. Grady, M. Paoloni, K. Krishnan, M. Carducci
Journal: Annals of Oncology (2020)
352TiP EPIK-B2: A phase III study of alpelisib (ALP) as maintenance therapy with trastuzumab (T) and pertuzumab (P) in patients (pts) with PIK3CA-mutated (mut) human epidermal growth factor receptor-2–positive (HER2+) advanced breast cancer (ABC)
Authors: S.A. Hurvitz, S.K.L. Chia, E.M. Ciruelos, X. Hu, S-A. Im, W. Janni, G. Jerusalem, M. Lacouture, R. O'Regan, H.S. Rugo, Y.S. Yap, F. Ghaznawi, Y. Han, F. Su, S. Chandarlapaty
Journal: Annals of Oncology (2020)
Manipulating immune system using nanoparticles for an effective cancer treatment: Combination of targeted therapy and checkpoint blockage miRNA
Authors: Hanh Thuy Nguyen, Cao Dai Phung, Tuan Hiep Tran, Tung Thanh Pham, Le Minh Pham, Tiep Tien Nguyen, Jee-Heon Jeong, Han-Gon Choi, Sae Kwang Ku, Chul Soon Yong, Jong Oh Kim
Journal: Journal of Controlled Release (2020)
1120P Post-approval trials versus patient registries: Comparability of advanced melanoma patients with brain metastases
Authors: R. Ismail, N. Sikkes, M. Wouters, D. Hilarius, M. Pasmooij, F. van den Eertwegh, M. Aarts, F. Van den Berkmortel, M. Boers-Sonderen, J.W.B. de Groot, J.B.A.G. Haanen, G.A.P. Hospers, E. Kapiteijn, D. Piersma, R. van Rijn, K.P.M. Suijkerbuijk, A.J. ten Tije, A.A.M. Van der Veldt, G. Vreugdenhil, M. van Dartel
Journal: Annals of Oncology (2020)
Systematic evaluation and external validation of 22 prognostic models among hospitalised adults with COVID-19: an observational cohort study
Authors: Rishi K. Gupta, Michael Marks, Thomas H.A. Samuels, Akish Luintel, Tommy Rampling, Humayra Chowdhury, Matteo Quartagno, Arjun Nair, Marc Lipman, Ibrahim Abubakar, Maarten van Smeden, Wai Keong Wong, Bryan Williams, Mahdad Noursadeghi
Journal: European Respiratory Journal (2020)

The number of proposed prognostic models for coronavirus disease 2019 (COVID-19) is growing rapidly, but it is unknown whether any are suitable for widespread clinical implementation. We independently externally validated the performance of candidate prognostic models, identified through a living systematic review, among consecutive adults admitted to hospital with a final diagnosis of COVID-19. We reconstructed candidate models as per original descriptions and evaluated performance for their original intended outcomes using predictors measured at the time of admission. We assessed discrimination, calibration and net benefit, compared to the default strategies of treating all and no patients, and against the most discriminating predictors in univariable analyses. We tested 22 candidate prognostic models among 411 participants with COVID-19, of whom 180 (43.8%) and 115 (28.0%) met the endpoints of clinical deterioration and mortality, respectively. Highest areas under receiver operating characteristic (AUROC) curves were achieved by the NEWS2 score for prediction of deterioration over 24 h (0.78, 95% CI 0.73–0.83), and a novel model for prediction of deterioration &lt;14 days from admission (0.78, 95% CI 0.74–0.82). The most discriminating univariable predictors were admission oxygen saturation on room air for in-hospital deterioration (AUROC 0.76, 95% CI 0.71–0.81), and age for in-hospital mortality (AUROC 0.76, 95% CI 0.71–0.81). No prognostic model demonstrated consistently higher net benefit than these univariable predictors, across a range of threshold probabilities. Admission oxygen saturation on room air and patient age are strong predictors of deterioration and mortality among hospitalised adults with COVID-19, respectively. None of the prognostic models evaluated here offered incremental value for patient stratification to these univariable predictors.
1162MO Efficacy and safety of lanreotide autogel (LAN) 120 mg every 14 days in progressive pancreatic or midgut neuroendocrine tumours (NETs): CLARINET FORTE study results
Authors: M. Pavel, J.B. Ćwikła, C. Lombard-Bohas, I. Borbath, T. Shah, U-F. Pape, X-M. Truong Thanh, A. Houchard, P. Ruszniewski
Journal: Annals of Oncology (2020)
1094P Demographics, prior therapies and reasons for cemiplimab treatment: Prospective cemiplimAb-rwlc survivorship and epidemiology (C.A.S.E.) study in patients with advanced cutaneous squamous cell carcinoma (CSCC)
Authors: G. Rabinowits, J. Homsi, M. Nikanjam, R. Gentry, J. Strasswimmer, S. Venna, M.R. Migden, S. Chandra, E. Ruiz, H.R. Zhang, J. McGinniss, A. Seluzhytsky, J. Desai
Journal: Annals of Oncology (2020)
938P Nutritional status (NS) as a strong predictor for immunotherapy (IT) outcome in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients (pts)
Authors: A. Hernando-Calvo, O. Mirallas, D.H. Marmolejo Castaneda, M. Vieito, O. Saavedra Santa Gadea, I. Gardeazabal, G. Villacampa Javierre, S. Aguilar, J. Martin Liberal, C. Bescós, J. Lorente, J. Giralt, S. Benavente, J.F. Fuentes, J. Temprana-Salvador, M. Alberola, R. Dienstmann, E. Garralda, E. Felip, I. Braña
Journal: Annals of Oncology (2020)