tbuckley/cabot-search huggingface dataset:
Abstract P3-08-61: The association of disease free survival and the impact of tumor subtype on overall survival in advanced breast cancer patients: A real-world study from the China National Cancer Center
Authors: Yiqun Li, Binghe Xu, Fei Ma, Qing Li, Pin Zhang, Peng Yuan, Jiayu Wang, Yang Luo, Ruigang Cai, Qiao Li, Hongnan Mo, Xiuwen Guan, Shaoyan Lin, Yimeng Chen, Zijing Wang
Journal: Cancer Research (2020)

Abstract Objective: In breast cancer, tumor subtype and disease free survival (DFS) are correlated with prognosis. The aim of this study was to assess whether the effect of tumor subtype on survival was associated with DFS. Methods: The China National Cancer Center database was used to identify 1784 breast cancer women diagnosed between January 1987 to June 2017. Overall survival (OS) was defined as the time from first tumor recurrence or relapse to death due to any cause. Eligibility required metastatic patients with documented ER, PR, and HER2 status. Tumor subtype was classified into four groups: HR+HER2-, HR+HER2+, HR-HER2+ and triple negative breast cancer (TNBC) group. Results: In patients whose DFS &amp;lt; 2 years, we found significant differences between tumor subtype and OS (P=0.007), with HR+HER2- presenting most favorable survival while TNBC showing worst prognosis. A similar pattern was observed in patients whose DFS &amp;lt; 3, 4 and 5 years (all P&amp;lt;0.001). However, when disease recurrence occurred within 1 year, no differences in survival were observed among tumor subtypes (P=0.508). Subsequent first-line treatment analysis in the overall ‘DFS&amp;lt; 1 year’ group and the four subtype groups showed that combined chemotherapy did not significantly improve patient survival compared with single agent chemotherapy (all P&amp;gt; 0.1). Of note, if DFS was longer than five years, the impact of different tumor subtype on survival was not obvious (P=0.438). Conclusion: No survival differences were found among tumor subtypes when DFS was shorter than one year, indicating particularly poor prognosis even in the HR+HER2- subtype, possibly due to primary treatment resistance. Subsequent more intensive first-line treatment with combined chemotherapy might not help in prolonging survival. Citation Format: Yiqun Li, Binghe Xu, Fei Ma, Qing Li, Pin Zhang, Peng Yuan, Jiayu Wang, Yang Luo, Ruigang Cai, Qiao Li, Hongnan Mo, Xiuwen Guan, Shaoyan Lin, Yimeng Chen, Zijing Wang. The association of disease free survival and the impact of tumor subtype on overall survival in advanced breast cancer patients: A real-world study from the China National Cancer Center [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-61.
The Prognostic Significance of Quantitative Myocardial Perfusion: An Artificial Intelligence Based Approach Using Perfusion Mapping
Authors: Kristopher D. Knott, Andreas Seraphim, Joao B. Augusto, Hui Xue, Liza Chacko, Nay Aung, Steffen E. Petersen, Jackie A. Cooper, Charlotte Manisty, Anish N. Bhuva, Tushar Kotecha, Christos V. Bourantas, Rhodri H. Davies, Louise A.E. Brown, Sven Plein, Marianna Fontana, Peter Kellman, James C. Moon
Journal: Circulation (2020)

Background: Myocardial perfusion reflects the macro- and microvascular coronary circulation. Recent quantitation developments using cardiovascular magnetic resonance (CMR) perfusion permit automated measurement clinically. We explored the prognostic significance of stress myocardial blood flow (MBF) and myocardial perfusion reserve (MPR, the ratio of stress to rest MBF). Methods: A two center study of patients with both suspected and known coronary artery disease referred clinically for perfusion assessment. Image analysis was performed automatically using a novel artificial intelligence approach deriving global and regional stress and rest MBF and MPR. Cox proportional hazard models adjusting for co-morbidities and CMR parameters sought associations of stress MBF and MPR with death and major adverse cardiovascular events (MACE), including myocardial infarction, stroke, heart failure hospitalization, late (&gt;90 day) revascularization and death. Results: 1049 patients were included with median follow-up 605 (interquartile range 464-814) days. There were 42 (4.0%) deaths and 188 MACE in 174 (16.6%) patients. Stress MBF and MPR were independently associated with both death and MACE. For each 1ml/g/min decrease in stress MBF the adjusted hazard ratio (HR) for death and MACE were 1.93 (95% CI 1.08-3.48, P=0.028) and 2.14 (95% CI 1.58-2.90, P&lt;0.0001) respectively, even after adjusting for age and co-morbidity. For each 1 unit decrease in MPR the adjusted HR for death and MACE were 2.45 (95% CI 1.42-4.24, P=0.001) and 1.74 (95% CI 1.36-2.22, P&lt;0.0001) respectively. In patients without regional perfusion defects on clinical read and no known macrovascular coronary artery disease (n=783), MPR remained independently associated with death and MACE, with stress MBF remaining associated with MACE only. Conclusions: In patients with known or suspected coronary artery disease, reduced MBF and MPR measured automatically inline using artificial intelligence quantification of CMR perfusion mapping provides a strong, independent predictor of adverse cardiovascular outcomes.
Genomic characterization of diffuse large B-cell lymphoma transformation of nodular lymphocyte-predominant Hodgkin lymphoma
Authors: Joo Y. Song, Caoimhe Egan, Alyssa C. Bouska, Weiwei Zhang, Qiang Gong, Girish Venkataraman, Alex F. Herrera, Lu Chen, Rebecca Ottesen, Joyce C. Niland, Victoria Bedell, Maria Valle-Catuna, Joyce Murata-Collins, Dennis D. Weisenburger, Javeed Iqbal, Elaine S. Jaffe, Wing C. Chan
Journal: Leukemia (2020)
Developmental plasticity allows outside-in immune responses by resident memory T cells
Authors: Raissa Fonseca, Lalit K. Beura, Clare F. Quarnstrom, Hazem E. Ghoneim, Yiping Fan, Caitlin C. Zebley, Milcah C. Scott, Nancy J. Fares-Frederickson, Sathi Wijeyesinghe, Emily A. Thompson, Henrique Borges da Silva, Vaiva Vezys, Benjamin Youngblood, David Masopust
Journal: Nature Immunology (2020)
RNA-based scaffolds for bone regeneration: application and mechanisms of mRNA, miRNA and siRNA
Authors: Qiuping Leng, Lini Chen, Yonggang Lv
Journal: Theranostics (2020)

Globally, more than 1.5 million patients undergo bone graft surgeries annually, and the development of biomaterial scaffolds that mimic natural bone for bone grafting remains a tremendous challenge.In recent decades, due to the improved understanding of the mechanisms of bone remodeling and the rapid development of gene therapy, RNA (including messenger RNA (mRNA), microRNA (miRNA), and short interfering RNA (siRNA)) has attracted increased attention as a new tool for bone tissue engineering due to its unique nature and great potential to cure bone defects.Different types of RNA play roles via a variety of mechanisms in bone-related cells in vivo as well as after synthesis in vitro.In addition, RNAs are delivered to injured sites by loading into scaffolds or systemic administration after combination with vectors for bone tissue engineering.However, the challenge of effectively and stably delivering RNA into local tissue remains to be solved.This review describes the mechanisms of the three types of RNAs and the application of the relevant types of RNA delivery vectors and scaffolds in bone regeneration.The improvements in their development are also discussed.
Unfolding innate mechanisms in the cancer microenvironment: The emerging role of the mesenchyme
Authors: Vasiliki Koliaraki, Ana Henriques, Alejandro Prados, George Kollias
Journal: The Journal of Experimental Medicine (2020)

Innate mechanisms in the tumor stroma play a crucial role both in the initial rejection of tumors and in cancer promotion. Here, we provide a concise overview of the innate system in cancer and recent advances in the field, including the activation and functions of innate immune cells and the emerging innate properties and modulatory roles of the fibroblastic mesenchyme. Novel insights into the diverse identities and functions of the innate immune and mesenchymal cells in the microenvironment of tumors should lead to improved anticancer therapies.
Time Course of Normalization of Functional β-Cell Capacity in the Diabetes Remission Clinical Trial After Weight Loss in Type 2 Diabetes
Authors: Sviatlana V. Zhyzhneuskaya, Ahmad Al-Mrabeh, Carl Peters, Alison Barnes, Benjamin Aribisala, Kieren G. Hollingsworth, Alex McConnachie, Naveed Sattar, Michael E.J. Lean, Roy Taylor
Journal: Diabetes Care (2020)

To assess functional β-cell capacity in type 2 diabetes during 2 years of remission induced by dietary weight loss.A Stepped Insulin Secretion Test with Arginine was used to quantify functional β-cell capacity by hyperglycemia and arginine stimulation. Thirty-nine of 57 participants initially achieved remission (HbA1c <6.5% [<48 mmol/mol] and fasting plasma glucose <7 mmol/L on no antidiabetic drug therapy) with a 16.4 ± 7.7 kg weight loss and were followed up with supportive advice on avoidance of weight regain. At 2 years, 20 participants remained in remission in the study. A nondiabetic control (NDC) group, matched for age, sex, and weight after weight loss with the intervention group, was studied once.During remission, median (interquartile range) maximal rate of insulin secretion increased from 581 (480-811) pmol/min/m2 at baseline to 736 (542-998) pmol/min/m2 at 5 months, 942 (565-1,240) pmol/min/m2 at 12 months (P = 0.028 from baseline), and 936 (635-1,435) pmol/min/m2 at 24 months (P = 0.023 from baseline; n = 20 of 39 of those initially in remission). This was comparable to the NDC group (1,016 [857-1,507] pmol/min/m2) by 12 (P = 0.064) and 24 (P = 0.244) months. Median first-phase insulin response increased from baseline to 5 months (42 [4-67] to 107 [59-163] pmol/min/m2; P < 0.0001) and then remained stable at 12 and 24 months (110 [59-201] and 125 [65-166] pmol/min/m2, respectively; P < 0.0001 vs. baseline) but lower than that of the NDC group (250 [226-429] pmol/min/m2; P < 0.0001).A gradual increase in assessed functional β-cell capacity occurred after weight loss, becoming similar to that of NDC group participants by 12 months. This result was unchanged at 2 years with continuing remission of type 2 diabetes.
Inflammatory extracellular vesicles prompt heart dysfunction via TRL4-dependent NF-κB activation
Authors: Vanessa Biemmi, Giuseppina Milano, Alessandra Ciullo, Elisabetta Cervio, Jacopo Burrello, Michele Dei Cas, Rita Paroni, Tiziano Tallone, Tiziano Moccetti, Giovanni Pedrazzini, Sarah Longnus, Giuseppe Vassalli, Lucio Barile
Journal: Theranostics (2020)

Background: After myocardial infarction, necrotic cardiomyocytes release damage-associated proteins that stimulate innate immune pathways and macrophage tissue infiltration, which drives inflammation and myocardial remodeling. Circulating inflammatory extracellular vesicles play a crucial role in the acute and chronic phases of ischemia, in terms of inflammatory progression. In this study, we hypothesize that the paracrine effect mediated by these vesicles induces direct cytotoxicity in cardiomyocytes. Thus, we examined whether reducing the generation of inflammatory vesicles within the first few hours after the ischemic event ameliorates cardiac outcome at short and long time points. Methods: Myocardial infarction was induced in rats that were previously injected intraperitoneally with a chemical inhibitor of extracellular-vesicle biogenesis. Heart global function was assessed by echocardiography performed at 7, 14 and 28 days after MI. Cardiac outcome was also evaluated by hemodynamic analysis at sacrifice. Cytotoxic effects of circulating EV were evaluated ex-vivo in a Langendorff, system by measuring the level of cardiac troponin I (cTnI) in the perfusate. Mechanisms undergoing cytotoxic effects of EV derived from pro-inflammatory macrophages (M1) were studied in-vitro in primary rat neonatal cardiomyocytes. Results: Inflammatory response following myocardial infarction dramatically increased the number of circulating extracellular vesicles carrying alarmins such as IL-1α, IL-1β and Rantes. Reducing the boost in inflammatory vesicles during the acute phase of ischemia resulted in preserved left ventricular ejection fraction in vivo. Hemodynamic analysis confirmed functional recovery by displaying higher velocity of left ventricular relaxation and improved contractility. When added to the perfusate of isolated hearts, post-infarction circulating vesicles induced significantly more cell death in adult cardiomyocytes, as assessed by cTnI release, comparing to circulating vesicles isolated from healthy (non-infarcted) rats. In vitro inflammatory extracellular vesicles induce cell death by driving nuclear translocation of NF-κB into nuclei of cardiomyocytes. Conclusion: Our data suggest that targeting circulating extracellular vesicles during the acute phase of myocardial infarction may offer an effective therapeutic approach to preserve function of ischemic heart.
PF607 MAINTENANCE WITH WEEKLY CARFILZOMIB IN ELDERLY NEWLY DIAGNOSED MULTIPLE MYELOMA (IFM 2012–03)
Authors: A. Bobin, G. Fouquet, A. Duhamel, L. Karlin, B. Kolb, M. Tiab, P. Bourquard, P. Lenain, A. Jaccard, K. Belhadj‐Merzoug, M. Attal, P. Moreau, C. Hulin, T. Facon, H. Avet‐Loiseau, X. Leleu
Journal: HemaSphere (2019)

Background: Continuous therapy, such as maintenance, appears to be a major therapeutic change in multiple myeloma, improving response rate and overall survival. Novel agents widen the range of treatment options, but still Lenalidomide (IMIiD) is widely used in this indication. Even though usually well tolerated it remains a daily treatment, and thus can lead to some side effects on a long term basis. Carfilzomib, a second generation PI, allows interesting response rate and prolonged survival, with manageable adverse events. Nevertheless, only few clinical trials focused on its use in maintenance rather than in first or second line treatment. Aims: Thereforewe, we chose to study maintenance Carfilzomib for elderly newly diagnosed multiple myeloma (eNDMM). Methods: IFM 2012–03 is a multicenter phase I study for eNDMM (patients aged 65 years old and more) that determined the maximal tolerated dose of weekly carfilzomib, associated with melphalan and prednisone (KMP), at 70 mg/m 2 . The following results will concern the second phase of the study using intravenous Carfilzomib monotherapy in maintenance. K was administered at 36 mg/m 2 for 13 cycles on an every 2 weeks schedule. Results: Thirty eNDMM were recruited in IFM 2012–03. Median age is 75, with 56% R‐ISS 2 or 3 and 11% high‐risk cytogenetic. With K weekly from 36 to 70 mg/m 2 , OS is reported at 93.3%, including 46.7% ≥CR; median PFS is 35.8 months and median OS was not reached. Twenty‐two (73%) patients started K maintenance and 16 (73%) completed it. Four patients progressed and 2 stopped for AEs (renal amylosis, sensory neuropahty) during the maintenance phase. At maintenance completion, 50% were ≥CR. From the start of maintenance, in landmark analysis, median PFS is 28.1 months and the estimated 36‐months OS approximately 70%. Summary/Conclusion: Maintenance Carfilzomib enables deep responses as well as prolonged survival for patients over 65 years old presenting with a newly diagnosed multiple myeloma. With promising results, a fixed duration and a satisfying safety profile it could integrate new treatment strategies for ineligible to transplant NDMM. Surely patients could benefit of its efficacy in addition to simple administration modality. Further studies should still bring additional informations in order to confirm our results. Nowadays, multiple myeloma treatment landscape and clinical practice is constantly evolving leading to significant improvement for our patients.
In-Hospital Outcomes and Discharge Medication Use Among Patients With Critical Limb Ischemia Versus Claudication
Authors: Jennifer A. Rymer, Kevin F. Kennedy, Angela M. Lowenstern, Eric A. Secemsky, Thomas T. Tsai, Herbert D. Aronow, Anand Prasad, Bruce Gray, Ehrin J. Armstrong, Kenneth Rosenfield, Mehdi H. Shishehbor, W. Schuyler Jones
Journal: Journal of the American College of Cardiology (2020)
Cardiovascular Risk in Clopidogrel-Treated Patients According to Cytochrome P450 2C19*2 Loss-of-Function Allele or Proton Pump Inhibitor Coadministration
Authors: Jean-Sébastien Hulot, Jean-Philippe Collet, Johanne Silvain, Ana Pena, Anne Bellemain-Appaix, Olivier Barthélémy, Guillaume Cayla, Farzin Beygui, Gilles Montalescot
Journal: Journal of the American College of Cardiology (2010)
Glen Harrison Lowther
Authors: Marj Lowther, Dorothy Groghan, Shannon Dutson
Journal: BMJ (2020)

Glen Harrison Lowther had a profound effect on the lives of the thousands of patients he cared for, and his legacy continues. Raised and educated in Glasgow, this proud Scot basked in the poetry, history, landscape, and music of his homeland. His childhood vacation spot of Tarbert, Loch Fyne, was his most cherished memory, so much so that he continued to visit Tarbert on every trip to Scotland.

After graduating from the University of Glasgow, he spent a year working in internal medicine and psychiatry at Glasgow’s teaching hospitals before going into the Royal Army Medical Corps. While at university he was president of the student union and a prize winning debater. According to family folklore, his most famous speech advised students, “If work gets in the way of the corporate life of the university, then work must go!”

He emigrated to Manitoba, Canada, in 1952 and joined the staff of what is now the Manitoba …
Abstract P3-11-21: Identification and characterization of novel splice variants in triple-negative breast cancer
Authors: Gayatri Arun, Priyanka Dhingra, Robin Munch, Vanessa Fredrick, Martin Akerman
Journal: Cancer Research (2020)

Abstract Splicing deregulation is a major hallmark of cancer, affecting progression, metastasis and therapy resistance. Multiple studies have demonstrated the oncogenic activity of specific splicing events and splicing factors, including SRSF1, SRSF2, ESRP1, and RBFOX1, in human and animal models. As such, cancer-associated splicing deregulation may be a novel source of clinically-applicable biomarkers and therapeutic targets, particularly for treatment-insensitive cancers such as TNBC. Here, we identified and experimentally characterized novel splicing changes in triple negative breast cancer by analyzing TCGA breast cancer RNA-seq data using our software platform SpliceCore. SpliceCore integrates machine learning (ML) algorithms with high-performance computing to analyze large RNA-Seq datasets to predict biologically relevant splicing events. Our analysis of TCGA BRCA datasets has revealed several previously unknown splicing events specific to TNBC patient cohorts, that is subsequently experimentally validated in TNBC cell lines. We provide biological evidence for such TNBC specific splice-switch both at the RNA and protein level. We provide evidence for SpliceCore predicted splice-switching oligonucleotides (SSO) and verify their biological activity in TNBC cell lines. Further, functional studies using potent and specific SSOs against the top candidates reveal a critical role for some of these novel isoforms in TNBC. Together, we provide a proof of concept study using SpliceCore to identify, design, and target novel splicing changes for subsequent clinical translation and therapeutic development. Citation Format: Gayatri Arun, Priyanka Dhingra, Robin Munch, Vanessa Fredrick, Martin Akerman. Identification and characterization of novel splice variants in triple-negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-11-21.
Arousal-induced cortical activity triggers lactate release from astrocytes
Authors: Marc Zuend, Aiman S. Saab, Matthias T. Wyss, Kim David Ferrari, Ladina Hösli, Zoe J. Looser, Jillian L. Stobart, Jordi Duran, Joan J. Guinovart, L. Felipe Barros, Bruno Weber
Journal: Nature Metabolism (2020)
Alginate oligosaccharides improve germ cell development and testicular microenvironment to rescue busulfan disrupted spermatogenesis
Authors: Yong Zhao, Pengfei Zhang, Wei Ge, Yanni Feng, Lan Li, Zhongyi Sun, Hongfu Zhang, Wei Shen
Journal: Theranostics (2020)

Rationale: Busulfan is currently an indispensable anti-cancer drug, particularly for children, but the side effects on male reproduction are so serious that critical drug management is needed to minimize any negative impact. Meanwhile, alginate oligosaccharides (AOS) are natural products with many consequent advantages, that have attracted a great deal of pharmaceutical attention. In the current investigation, we performed single-cell RNA sequencing on murine testes treated with busulfan and/or AOS to define the mitigating effects of AOS on spermatogenesis at the single cell level. Methods: Testicular cells (in vivo) were examined by single cell RNA sequencing analysis, histopathological analysis, immunofluorescence staining, and Western blotting. Testes samples (ex vivo) underwent RNA sequencing analysis. Blood and testicular metabolomes were determined by liquid chromatography-mass spectrometry (LC/MS). Results: We found that AOS increased murine sperm concentration and motility, and rescued busulfan disrupted spermatogenesis through improving (i) the proportion of germ cells, (ii) gene expression important for spermatogenesis, and (iii) transcriptional factors in vivo. Furthermore, AOS promoted the ex vivo expression of genes important for spermatogenesis. Finally, our results showed that AOS improved blood and testis metabolomes as well as the gut microbiota to support the recovery of spermatogenesis. Conclusions: AOS could be used to improve fertility in patients undergoing chemotherapy and to combat other factors that induce infertility in humans.
Poxvirus Vectored Cytomegalovirus Vaccine to Prevent Cytomegalovirus Viremia in Transplant Recipients
Authors: Ibrahim Aldoss, Corinna La Rosa, Lindsey R. Baden, Jeffrey Longmate, Ella J. Ariza-Heredia, Wasima N. Rida, Chetan Raj Lingaraju, Qiao Zhou, Joy Martinez, Teodora Kaltcheva, Andy Dagis, Nicola Hardwick, Nicolas C. Issa, Len Farol, Auayporn Nademanee, Monzr M. Al Malki, Stephen Forman, Ryotaro Nakamura, Don J. Diamond
Journal: Annals of Internal Medicine (2020)

Triplex vaccine was developed to enhance cytomegalovirus (CMV)-specific T cells and prevent CMV reactivation early after hematopoietic stem cell transplant (HCT).
Decellularized liver as a translucent ex vivo model for vascular embolization evaluation
Authors: Yanan Gao, Zhihua Li, Yin Hong, Tingting Li, Xiaoyan Hu, Luyao Sun, Zhengchang Chen, Zijian Chen, Zhiheng Luo, Xin Wang, Jian Kong, Guanglei Li, Hsing-Lin Wang, Hwa Liang Leo, Hanry Yu, Lei Xi, Qiongyu Guo
Journal: Biomaterials (2020)
Dual Inhibition of MCL1 and BCL2 in Lymphoma Using Tumor Targeted Nanoparticles
Authors: Neeta Bala Bala, Mandana Taghizadeh Manzari, Mariana Da Silva Ferreira, Zahra Asgari, Connor Hagen, Venkatraman Seshan, Elisa de Stanchina, Katia Manova-Todorova, Daniel Heller, Anas Younes
Journal: Blood (2019)