tbuckley/cabot-search huggingface dataset:
Abstract SP087: Epigenetic therapy against high-risk breast cancer
Authors: M Lupien
Journal: Cancer Research (2021)

Abstract Standard-of-care therapy in high-risk stage II-III ER+/HER2-negative and Triple-Negative Breast Cancer (TNBC) includes neoadjuvant chemotherapy (NAC) prior to surgery, which is then followed by adjuvant endocrine (for ER+) +/- salvage chemotherapy (for TNBC). These treatments are delivered with limited stratification by disease histology and, while many patients are cured, more than one third of those in whom invasive disease remains in the breast at the time of surgery experience early relapses of metastatic disease within the first few years. The poor survival rate stems from incomplete response to NAC and the lack of alternative tailored therapy against the chemo-resistant disease that recurs. Hence, there is an urgent need for new therapies to treat recurrence and improve outcome. Tumor progression following standard-of-care therapy arises from pre-existing resistant and/or adapting persister cancer cells committing to an expansion phase. These differ from treatment sensitive cells in the epigenetic landscape of their genome, regulating the on/off state of genes for instance. This underlies epigenetic variants, akin to genetic variants, that define vulnerabilities to new treatment strategies. Here, we demonstrate the value of epigenetic therapy in preclinical settings against high-risk breast cancer, putting forward new treatment options to be tested in clinical trials. Citation Format: M Lupien. Epigenetic therapy against high-risk breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SP087.
Management of Patients With Giant Cell Myocarditis
Authors: Vigyan Bang, Sarju Ganatra, Sachin P. Shah, Sourbha S. Dani, Tomas G. Neilan, Paaladinesh Thavendiranathan, Frederic S. Resnic, Thomas C. Piemonte, Ana Barac, Rushin Patel, Ajay Sharma, Rohan Parikh, Ghulam M. Chaudhry, Mark Vesely, Salim S. Hayek, Monika Leja, David Venesy, Richard Patten, Daniel Lenihan, Anju Nohria, Leslie T. Cooper
Journal: Journal of the American College of Cardiology (2021)
Cervical Cancer Screening in Low- and Middle-Income Countries
Authors: Miriam Cremer, Karla Alfaro, Rachel Masch
Journal: JAMA (2021)

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The role of surgery in platinum-resistant ovarian cancer: A call to the scientific community
Authors: Marco Petrillo, Giulio Sozzi, Margherita Dessole, Giampiero Capobianco, Salvatore Dessole, Massimo Madonia, Pier Luigi Cherchi, Anna Maria Paoletti, Giovanni Scambia, Vito Chiantera
Journal: Seminars in Cancer Biology (2021)
Innate lymphoid cells: The missing part of a puzzle in food allergy
Authors: Umit M. Sahiner, Janice A. Layhadi, Korneliusz Golebski, Zsolt István Komlósi, Yaqi Peng, Bulent Sekerel, Stephen R. Durham, Helen Brough, Hideaki Morita, Mübeccel Akdis, Paul Turner, Kari Nadeau, Hergen Spits, Cezmi Akdis, Mohamed H. Shamji
Journal: Allergy (2021)

Food allergy is an increasingly prevalent disease driven by uncontrolled type 2 immune response. Currently, knowledge about the underlying mechanisms that initiate and promote the immune response to dietary allergens is limited. Patients with food allergy are commonly sensitized through the skin in their early life, later on developing allergy symptoms within the gastrointestinal tract. Food allergy results from a dysregulated type 2 response to food allergens, characterized by enhanced levels of IgE, IL-4, IL-5, and IL-13 with infiltration of mast cells, eosinophils, and basophils. Recent studies raised a possible role for the involvement of innate lymphoid cells (ILCs) in driving food allergy. Unlike lymphocytes, ILCs lack They represent a group of lymphocytes that lack specific antigen receptors. ILCs contribute to immune responses not only by releasing cytokines and other mediators but also by responding to cytokines produced by activated cells in their local microenvironment. Due to their localization at barrier surfaces of the airways, gut, and skin, ILCs form a link between the innate and adaptive immunity. This review summarizes recent evidence on how skin and gastrointestinal mucosal immune system contribute to both homeostasis and the development of food allergy, as well as the involvement of ILCs toward inflammatory processes and regulatory mechanisms.
Abstract PS11-23: Current landscape in phase 3 trials in breast cancer at major oncology conferences
Authors: Gustavo Oliveira Bretas, José Bines, Everardo Delforge Saad
Journal: Cancer Research (2021)

Abstract Background: The oral presentation of studies at conferences may impact treatment practice even before the publication or regulatory approval. Methodological aspects and reporting patterns are evolving, and an assessment of these features may help understand the current landscape and the way forward. Methods: We analyzed the characteristics of primary analyses of phase 3 trials from oral sessions presented at ASCO, ESMO and SABCS 2017-19 and the timing of their subsequent publications. We excluded non-inferiority trials and duplicate presentations within the period. Results: Of 36 unique trials, 19/10/7 had a first author from Europe/United States/Asia or elsewhere, and 21/15 were in the (neo)adjuvant/palliative settings. All but one trial had 2 arms. The number of patients enrolled ranged from 226 to 4884 (median, 646). All but 2 trials were on systemic therapy, with 16 dedicated exclusively to hormone-receptor+, 8 to HER2+ and 6 to triple-negative disease. According to the authors, 23 (63.9%, 95% CI, 46.2 to 79.2%) trials were positive, and 13 were negative. For only 2 of the negative trials was the conclusion not entirely consistent with results. When sponsor information was available, 18/21 industry vs 4/14 academic trials were positive (P=0.002). Paradoxically, negative trials were larger than positive trials (medians of 2639 and 585 patients; P=0.002), perhaps because all but one of 13 negative trials were in the (neo)adjuvant setting, vs 9/23 among positive trials (P=0.004). The time to publication was significantly shorter for positive than negative trials (medians of 215 vs 785 days; HR=0.32; P=0.013). Of 30 trials with time-to-event endpoints, the ratio between observed:expected HR could be computed for 24: the mean was 0.88 for 15 positive and 1.43 for 9 negative trials (P=0.004; 1.09 overall). Conclusion: In recent phase 3 trials in breast cancer, positive trials are more likely than negative trials to be industry-sponsored, to assess the metastatic setting, and to be published earlier. These results also suggest that the treatment effect has been underestimated in positive trials. Research is ongoing to elucidate potential determinants of the latter hypothesis. Citation Format: Gustavo Oliveira Bretas, José Bines, Everardo Delforge Saad. Current landscape in phase 3 trials in breast cancer at major oncology conferences [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS11-23.
Abnormalities in Mitochondrial DNA Copy Number Have Pathogenetic and Prognostic Implications in Multiple Myeloma
Authors: Yanira Ruiz-Heredia, Mehmet Kemal Samur, Alejandra Ortiz-Ruiz, Rafael Alonso Fernández, Beatriz Sanchez-Vega, Alberto Blazquez, Aitor Delmiro, Jose Carlos Martinez-Avila, Esther Onecha, Antonio Valeri, Miguel Angel Martin, Niccolo Bolli, Yu-Tzu Tai, Francesco Maura, Raphael Szalat, Mariateresa Fulciniti, María Linares, Miguel Gallardo, Peter J Campbell, Hervé Avet-Loiseau, Juan Jose Lahuerta, Nikhil Munshi, Joaquin Martinez-Lopez
Journal: Blood (2017)
BH3 profiling identifies ruxolitinib as a promising partner for venetoclax to treat T-cell prolymphocytic leukemia
Authors: Charles Herbaux, Christoph Kornauth, Stéphanie Poulain, Stephen J. F. Chong, Mary C. Collins, Rebecca Valentin, Liam Hackett, Olivier Tournilhac, François Lemonnier, Jehan Dupuis, Adrien Daniel, Cecile Tomowiak, Kamel Laribi, Loïc Renaud, Damien Roos-Weil, Cedric Rossi, Eric Van Den Neste, Cecile Leyronnas, Fatiha Merabet, Jean Valère Malfuson, Mourad Tiab, Loïc Ysebaert, Samuel Ng, Franck Morschhauser, Philipp B. Staber, Matthew S. Davids
Journal: Blood (2021)
Multiple cell types contribute to the atherosclerotic lesion fibrous cap by PDGFRβ and bioenergetic mechanisms
Authors: Alexandra A. C. Newman, Vlad Serbulea, Richard A. Baylis, Laura S. Shankman, Xenia Bradley, Gabriel F. Alencar, Katherine Owsiany, Rebecca A. Deaton, Santosh Karnewar, Sohel Shamsuzzaman, Anita Salamon, Mahima S. Reddy, Liang Guo, Aloke Finn, Renu Virmani, Olga A. Cherepanova, Gary K. Owens
Journal: Nature Metabolism (2021)
A TNFR2–hnRNPK Axis Promotes Primary Liver Cancer Development via Activation of YAP Signaling in Hepatic Progenitor Cells
Authors: Yan Meng, Qiudong Zhao, Liwei An, Shi Jiao, Rong Li, Yan Sang, Jianping Liao, Pingping Nie, Fuping Wen, Junyi Ju, Zhaocai Zhou, Lixin Wei
Journal: Cancer Research (2021)

Most primary liver cancer (PLC) cases progress mainly due to underlying chronic liver inflammation, yet the underlying mechanisms of inflammation-mediated PLC remain unclear. Here we uncover a TNF receptor II (TNFR2)-hnRNPK-YAP signaling axis in hepatic progenitor cells (HPC) essential for PLC development. TNFR2, but not TNF receptor I (TNFR1), was required for TNFα-induced activation of YAP during malignant transformation of HPCs and liver tumorigenesis. Mechanistically, heterogeneous nuclear ribonuclear protein K (hnRNPK) acted downstream of TNFα-TNFR2 signaling to directly interact with and stabilize YAP on target gene promoters genome-wide, therefore coregulating the expression of YAP target genes. Single-cell RNA sequencing confirmed the association of TNFR2-hnRNPK with YAP expression and the pathologic importance of HPC. Accordingly, expressions of TNFR2, hnRNPK, and YAP were all upregulated in PLC tissues and were strongly associated with poor prognosis of PLC including patient survival. Collectively, this study clarifies the differential roles of TNFRs in HPC-mediated tumorigenesis, uncovering a TNFR2-hnRNPK-centered mechanistic link between the TNFα-mediated inflammatory milieu and YAP activation in HPCs during PLC development. SIGNIFICANCE: This work defines how hnRNPK links TNFα signaling and Hippo pathway transcription coactivator YAP in hepatic progenitor cells during primary liver tumorigenesis.
Case 6-2021: A 65-Year-Old Man with Eye Pain and Decreased Vision
Authors: Marc A. Bouffard, Bart K. Chwalisz, Javier M. Romero, Isabel C. Arrillaga-Romany, Lucas R. Massoth
Journal: New England Journal of Medicine (2021)

A 65-year-old man with Waldenström's macroglobulinemia was evaluated because of an 8-day history of bilateral eye pain and decreased vision. He had decreased visual acuity, dyschromatopsia, visual field loss, a relative afferent pupillary defect, and an abnormal appearance of the optic disk. A diagnosis was made.
Co-production of evidence for policies in Thailand: from concept to action
Authors: Viroj Tangcharoensathien, Supakit Sirilak, Piyamitr Sritara, Walaiporn Patcharanarumol, Angkana Lekagul, Wanrudee Isaranuwatchai, Woranan Wittayapipopsakul, Orana Chandrasiri
Journal: BMJ (2021)

Viroj Tangcharoensathien and colleagues apply the “triangle that moves the mountain” to analyse the co-production of evidence for health policy making in Thailand
Free Papers
Authors: R. J. B. J. Gerrite, G. J. Bonsel, A. J. van Vught, D. R. Goldhill, A. Vedio, F. Warburton, M. Griffiths, R. M. Leach, D. F. Treacher, U. Corbanese, R. Marcon, C. Possamai, L. Casagrande, A. Balsarin, A. Avila, J. L. Moran, M. E. Finnis, P. Leppard, B. Herman, B. Grealy, A. R. Peisach, S. Ridley, J. Rogers, P. Chrispin, H. Scotton, D. Lloyd, B. M. Livingston, F. N. MacKirdy, B. W. Millar, J. C. Howie, R. Moreno, P. Morais, M. Niskanen, E. Ruokonen, J. Takala, A. Kari, J. Bakker, J. H. Rommes, G. Dobb, J. Weekes, S. Edlin, S. Towler, K. Donovan, K. -Y. Lee, G. Clarke
Journal: Intensive Care Medicine (1996)
Computational Screening of Phase-Separating Proteins
Authors: Boyan Shen, Zhaoming Chen, Chunyu Yu, Taoyu Chen, Minglei Shi, Tingting Li
Journal: Genomics Proteomics & Bioinformatics (2021)

Abstract Phase separation is an important mechanism that mediates the compartmentalization of proteins in cells. Proteins that can undergo phase separation in cells share certain typical sequence features, like intrinsically disordered regions (IDRs) and multiple modular domains. Sequence-based analysis tools are commonly used in the screening of these proteins. However, current phase separation predictors are mostly designed for IDR-containing proteins, thus inevitably overlook the phase-separating proteins with relatively low IDR content. Features other than amino acid sequence could provide crucial information for identifying possible phase-separating proteins: protein–protein interaction (PPI) networks show multivalent interactions that underlie phase separation process; post-translational modifications (PTMs) are crucial in the regulation of phase separation behavior; spherical structures revealed in immunofluorescence (IF)images indicate condensed droplets formed by phase-separating proteins, distinguishing these proteins from non-phase-separating proteins. Here, we summarize the sequence-based tools for predicting phase-separating proteins and highlight the importance of incorporating PPIs, PTMs, and IF images into phase separation prediction in future studies.
Abstract 3583: Increase of Lower Pacing Rate Reduces Cardiac Congestion in Patients with Heart Failure and CRT
Authors: Frieder Braunschweig, Hans-Juergen Bruns, Frederik Gadler, David Ersgard, Marcus Stahlberg, Pierre-Andre Grandjean, Michael Hill, Cecilia Linde
Journal: Circulation (2006)

Objective:CRT improves central hemodynamics in pts with HF and ventricular asynchrony. It is generally accepted that programming of CRT devices should be adjusted to achieve optimal hemodynamic out...
Abstract 18947: Ski Regulates ZEB2 via a Hippo-Dependent Mechanism in Rat Cardiac Fibroblasts
Authors: Natalie M Landry, Mark Hnatowich, Thomas Meier, Sunil G Rattan, Jeffrey T Wigle, Ian M Dixon
Journal: Circulation (2017)

Introduction: Quiescent cardiac fibroblasts are required for tissue homeostasis of the myocardium. Upon activation by various stressors, cardiac fibroblasts exhibit the hyper-secretory, hyper-proli...
Abstract PS9-60: Insomnia is the most disturbing symptom during breast cancer treatment: Results from a Brazilian cohort using a patient-reported outcomes: PRO tool - Tummi App
Authors: Alessandra Menezes Morelle, Fernando Castilho Venero, Rafael DalPonte Ferreira, Rommel FabricioPereirada Silva, Pedro Tofani Sant'Anna
Journal: Cancer Research (2021)

Abstract Background: PRO have been shown to enhance our ability to communicate with patients and to control their symptoms. There are data that suggest a positive impact on survival when there is active participation of the patient in the reporting of symptoms. However, PRO data are not commonly collected in routine cancer care due to challenges like cost and due to the obsolete technology of many existing electronic health records. Methods: in an effort to bridge the unmet needs of PRO collection and integration into routine cancer care, we developed a symptom monitoring and management system that was launched as a free mobile app in August, 2018. Tummi app is designed for reporting 28 symptoms based on the National Cancer Institute’s Common Terminology Criteria for Adverse Events. Symptoms are reported in a 3-point scale (mild, moderate, severe) and patient reported an overall well-being scale represented by emojis. Tummi has the ability to record symptoms, summarize the reporting in physical printout, and automatically store and analyze the input symptoms into graphical interpretations. Results: since august 2018, 281 patients with the diagnosis of invasive breast cancer, during their treatment, downloaded and enjoyed the app. The most common side effect registered was back pain. When assessing the most intense symptoms reported by patients (grade 3), insomnia appears as the most remembered, followed by headache. Regarding general well-being reports, patients totaled 4501 records. Of these, at 62.40% of the time the patients were well, while at 33.16% they were average and at 4.44% they felt bad. Conclusions: in this group of patients evaluated by the Tummi App, insomnia is the most disturbing symptom. Although it appears in the literature as quite prevalent in this scenario, we see that its approach to day-by-day oncology clinics is far from ideal. We believe that the monitoring by a PRO tool can lead to a greater effort to improve this symptom that has such an impact on the quality of life of our patients. Citation Format: Alessandra Menezes Morelle, Fernando Castilho Venero, Rafael DalPonte Ferreira, Rommel FabricioPereirada Silva, Pedro Tofani Sant'Anna. Insomnia is the most disturbing symptom during breast cancer treatment: Results from a Brazilian cohort using a patient-reported outcomes: PRO tool - Tummi App [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-60.
Clinical Features and Prognosis of Acute Cardiac Injury in Hospitalized Patients With Covid-19: A Retrospective Cohort Study
Authors: M. X. Xie, L. Zhang, Y. J. Xie, Y. T. Zhang, W. Sun, C. Wu, B. Wang, D. Q. Zhang, H. L. Yuan, Y. X. Zhang, H. Li, L. He, L. Cui, S. S. Zhu, M. Li, Y. W. Zhang, Y. Zhang, L. F. Wang, Y. Cai, R. Wang, Y. Yang, Y. M. Li, J. Wang, Y. L. Yang, Q. Lv
Journal: Circulation (2020)
The effect of train-the-colonoscopy-trainer course on colonoscopy quality indicators
Authors: Geir Hoff, Edoardo Botteri, Gert Huppertz-Hauss, Jan Magnus Kvamme, Øyvind Holme, Lars Aabakken, Stein Dahler, Asle W. Medhus, Ingrid Blomgren, Per Sandvei, Ole Darre-Næss, Øystein Kjellevold, Birgitte Seip
Journal: Endoscopy (2021)

Abstract Background Systematic training in colonoscopy is highly recommended; however, we have limited knowledge of the effects of “training-the-colonoscopy-trainer” (TCT) courses. Using a national quality register on colonoscopy performance, we aimed to evaluate the effects of TCT participation on defined quality indicators. Methods This observational study compared quality indicators (pain, cecal intubation, and polyp detection) between centers participating versus not participating in a TCT course. Nonparticipating centers were assigned a pseudoparticipating year to match their participating counterparts. Results were compared between first year after and the year before TCT (pseudo)participation. Time trends up to 5 years after TCT (pseudo)participation were also compared. Generalized estimating equation models, adjusted for age, sex, and bowel cleansing, were used. Results 11 participating and 11 nonparticipating centers contributed 18 555 and 10 730 colonoscopies, respectively. In participating centers, there was a significant increase in detection of polyps ≥ 5 mm, from 26.4 % to 29.2 % (P = 0.035), and reduction in moderate/severe pain experienced by women, from 38.2 % to 33.6 % (P = 0.043); no significant changes were found in nonparticipating centers. Over 5 years, 20 participating and 18 nonparticipating centers contributed 85 691 and 41 569 colonoscopies, respectively. In participating centers, polyp detection rate increased linearly (P = 0.003), and pain decreased linearly in women (P = 0.004). Nonparticipating centers did not show any significant time trend during the study period. Conclusions Participation in a TCT course improved polyp detection rates and reduced pain experienced by women. These effects were maintained during a 5-year follow-up.
Cezanne is a critical regulator of pathological arterial remodelling by targeting β-catenin signalling
Authors: Weiwei An, Le A Luong, Neil P Bowden, Mei Yang, Wei Wu, Xinmiao Zhou, Chenxin Liu, Kaiyuan Niu, Jun Luo, Cheng Zhang, Xiaolei Sun, Robin Poston, Li Zhang, Paul C Evans, Qingzhong Xiao
Journal: Cardiovascular Research (2021)

Pathological arterial remodelling including neointimal hyperplasia and atherosclerosis is the main underlying cause for occluding arterial diseases. Cezanne is a novel deubiquitinating enzyme, functioning as a NF-кB negative regulator, and plays a key role in renal inflammatory response and kidney injury induced by ischaemia. Here we attempted to examine its pathological role in vascular smooth muscle cell (VSMC) pathology and arterial remodelling.
The vasculature: a therapeutic target in heart failure?
Authors: Guillermo Luxán, Stefanie Dimmeler
Journal: Cardiovascular Research (2021)

Abstract It is well established that the vasculature plays a crucial role in maintaining oxygen and nutrients supply to the heart. Increasing evidence further suggests that the microcirculation has additional roles in supporting a healthy microenvironment. Heart failure is well known to be associated with changes and functional impairment of the microvasculature. The specific ablation of protective signals in endothelial cells in experimental models is sufficient to induce heart failure. Therefore, restoring a healthy endothelium and microcirculation may be a valuable therapeutic strategy to treat heart failure. This review article will summarize the current understanding of the vascular contribution to heart failure with reduced or preserved ejection fraction. Novel therapeutic approaches including next generation pro-angiogenic therapies and non-coding RNA therapeutics, as well as the targeting of metabolites or metabolic signalling, vascular inflammation and senescence will be discussed.