tbuckley/cabot-search huggingface dataset:
Hormonal Regulation of Semaphorin 7a in ER+ Breast Cancer Drives Therapeutic Resistance
Authors: Lyndsey S. Crump, Garhett L. Wyatt, Taylor R. Rutherford, Jennifer K. Richer, Weston W. Porter, Traci R. Lyons
Journal: Cancer Research (2020)

Abstract Approximately 70% of all breast cancers are estrogen receptor–positive (ER+ breast cancer), and endocrine therapy has improved survival for patients with ER+ breast cancer. However, up to half of these tumors recur within 20 years. Recurrent ER+ breast cancers develop resistance to endocrine therapy; thus, novel targets are needed to treat recurrent ER+ breast cancer. Here we report that semaphorin 7A (SEMA7A) confers significantly decreased patient survival rates in ER+ breast cancer. SEMA7A was hormonally regulated in ER+ breast cancer, but its expression did not uniformly decrease with antiestrogen treatments. Additionally, overexpression of SEMA7A in ER+ cell lines drove increased in vitro growth in the presence of estrogen deprivation, tamoxifen, and fulvestrant. In vivo, SEMA7A conferred primary tumor resistance to fulvestrant and induced lung metastases. Prosurvival signaling was identified as a therapeutic vulnerability of ER+SEMA7A+ tumors. We therefore propose that targeting this pathway with inhibitors of survival signaling such as venetoclax may prove efficacious for treating SEMA7A+ tumors. Significance: SEMA7A predicts for and likely contributes to poor response to standard-of-care therapies, suggesting that patients with SEMA7A+ER+ tumors may benefit from alternative therapeutic strategies.
Children and Young Adults Admitted to a NYC Children's Hospital Had a Similar Rate of Severe COVID-19 Coagulopathy As That Reported in Older Adults
Authors: William Beau Mitchell, Jennifer G. Davila, Janine Keenan, Jenai Jackson, Adit Tal, Kerry A Morrone, Ellen J Silver, Sarah H. O'Brien, Deepa Manwani
Journal: Blood (2020)
Open-Label, Phase 1 Study to Evaluate Duration of Severe Neutropenia after Same-Day Dosing of Eflapegrastim in Patients with Breast Cancer Receiving Docetaxel and Cyclophosphamide (NCT04187898)
Authors: Lee S. Schwartzberg, Jawad Francis, Hlalah Osama, Manuel Modiano, Jayaram Bharadwaj, Shanta Chawla, Gajanan Bhat, Francois Lebel, Nishan Tchekmedyian
Journal: Blood (2020)
Splenic Marginal Zone Lymphoma (SMZL) - Outcomes, Prognostic Factors and Risk-Adapted Therapy in Resource-Poor Settings: Data from a Latin American Retrospective Cohort
Authors: Luis Alberto de Padua Covas Lage, Felipe Faganelli Caboclo dos Santos, Kasys Meira Gervatauskas, Debora Levy, Frederico Rafael Moreira, Samuel Campanelli Freitas Couto, Hebert Fabricio Culler, Renata Oliveira Costa, Vanderson Rocha, Juliana Pereira
Journal: Blood (2020)
Immunological and virological markers during pegylated interferon therapy in HDV chronic hepatitis: any predictor of response?
Authors: Antonella Olivero, Gian Paolo Caviglia, Rossana Fontana, Maria Lorena Abate, Chiara Rosso, Giulia Troshina, Elisabetta Bugianesi, Giorgio Maria Saracco, Mario Rizzetto, Grazia Niro, Antonina Smedile, Alessia Ciancio
Journal: Journal of Hepatology (2020)
Safety of Palbociclib in Combination with Chemotherapy in Pediatric and Young Adult Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia and Lymphoma: A Children's Oncology Group Pilot Study
Authors: Elizabeth A. Raetz, David T. Teachey, Charles Minard, Xiaowei Liu, Robin Norris, Joel Reid, Thalia Beeles, Lia Gore, Elizabeth Fox, Mignon L. Loh, Brenda J. Weigel, William L. Carroll
Journal: Blood (2020)
A Radiomic Machine Learning Model to Predict Treatment Response to Methotrexate and Survival Outcomes in Primary Central Nervous System Lymphoma (PCNSL)
Authors: Omer M Ali, Sahil S Nalawade, Yin Xi, Ben Wagner, Alexander Mazal, Shane Ahlers, Syed M Rizvi, Farrukh T Awan, Kiran A Kumar, Neil B Desai, Joseph A Maldjian, Marco C Pinho, Praveen Ramakrishnan Geethakumari
Journal: Blood (2020)
A Phase 3, Open-Label, Randomized Study Evaluating the Efficacy and Safety of Navitoclax Plus Ruxolitinib Versus Best Available Therapy in Patients with Relapsed/Refractory Myelofibrosis (TRANSFORM-2)
Authors: Kimberley Dilley, Jason Harb, Muhammad Jalaluddin, Jessica E. Hutti, Jalaja Potluri
Journal: Blood (2020)
Alan Gibb: ENT surgeon with an interest in hearing loss and diseases of the ear
Authors: Rebecca Wallersteiner
Journal: BMJ (2020)

Credit: University of St Andrews

Alan Gibb, an internationally renowned ear, nose, and throat (ENT) surgeon, has died at the age of 101. Gibb was born in Aberdeen to parents who were both GPs. His mother, Elizabeth (nee Ewan), was the city’s first female GP, and there is a plaque to her memory in Aberdeen’s Chapel Street. With such a heritage, it seemed destined that Gibb should enter a career in medicine. Educated at Aberdeen Grammar School, he was the youngest of six siblings and outlived them all. Five of the siblings were in the medical profession, and two of them were GPs in Aberdeen. His two elder sisters, Margaret and Muriel, were both centenarians. Margaret was a GP who lived to 101 and Muriel, an otolaryngologist in Ayr, lived to 105.

On graduating from Aberdeen University, Gibb was first exposed to ENT medicine at Aberdeen Royal Infirmary. He served in the Royal Army Medical Corps in West Africa during the second world war as a specialist ear surgeon, achieving the rank of major. On his return, he qualified for the fellowship of the Royal College of Surgeons of Edinburgh. …
Gilteritinib Remains Clinically Active in Relapsed/Refractory <i>FLT3</i> Mutated AML Previously Treated with <i>FLT3</i> inhibitors
Authors: Yazan Numan, Zaid Abdel Rahman, Justin Grenet, Stephanie Boisclair, Jan Philipp Bewersdorf, Dylan Barth, Amer M. Zeidan, Musa Yilmaz, Shira Dinner, Yehuda E. Deutsch, Olga Frankfurt, Mark Litzow, Aref Al-Kali, James M. Foran, Lisa Z. Sproat, Borko Jovanovic, Naval Daver, Alexander E. Perl, Jessica K. Altman
Journal: Blood (2020)
COVID-19 in Heart Transplant Recipients
Authors: Tomaso Bottio, Lorenzo Bagozzi, Alessandro Fiocco, Matteo Nadali, Raphael Caraffa, Olimpia Bifulco, Matteo Ponzoni, Carlo Maria Lombardi, Marco Metra, Claudio Francesco Russo, Maria Frigerio, Gabriella Masciocco, Luciano Potena, Antonio Loforte, Davide Pacini, Giuseppe Faggian, Francesco Onorati, Sandro Sponga, Ugolino Livi, Attilio Iacovoni, Amedeo Terzi, Michele Senni, Mauro Rinaldi, Massimo Boffini, Matteo Marro, Vjola Jorgji, Massimiliano Carrozzini, Gino Gerosa
Journal: JACC Heart Failure (2020)
Abstract PO-037: Characterization of stemness and immunogenicity of cancer stem cells of intrahepatic cholangiocarcinoma
Authors: Jianyang Fu, Yunhua Zhu, Nichole A. McGrath, Maggie Cam, Changqing Xie
Journal: Cancer Research (2020)

Abstract Cholangiocarcinoma (CCA) is one of leading causes of cancer related mortality with limited treatment options. Cancer stem cells (CSCs) have been recognized as a critical driving force of CCA initiation and drug-resistance, representing an attractive and innovative therapeutic target. In this study, single-cell transcriptomic landscape of cancer biospecimens from 10 patients with intrahepatic cholangiocarcinoma (iCCA) were investigated. We characterized CSC in CCA subtypes and identified the differential genes between CSCs and malignant cells. We found that there is the heterogeneity of CSCs in iCCA in terms of stemness makers and immunity per se. Our study pointed to low immunity spectrum of CSCs of iCCA that contribute to immune evasion. We found that SPP1 gene is highly expressed compared to malignant cells in CSC, which indicated that Osteopontin, which is coded by SPP1, may acts as an immune checkpoint to suppress T cell activation and confer host tumor immune tolerance. Our analysis from TCGA database also confirmed that, stemness was strongly associated with cell native immunosuppressive pathway and SPP1 gene expression. Our data indicate that CSC evade innate immune suppression through induced SPP1 expression and Osteopontin may serve as a potential therapeutic intervention for CCA patients. Citation Format: Jianyang Fu, Yunhua Zhu, Nichole A. McGrath, Maggie Cam, Changqing Xie. Characterization of stemness and immunogenicity of cancer stem cells of intrahepatic cholangiocarcinoma [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-037.
Resourcing primary care to tackle covid-19: cooperation, not competition
Authors: Thomas C McAnea
Journal: BMJ (2020)

Coombes is absolutely right to point out that “GPs are in pole position to care for those who survive initial infection but are left with longlasting mental and physical effects” of covid-19.1 This is at the heart of what we do—provide ongoing care for our population in the community. She …
Potential Disease-Modifying Activity of Imetelstat Demonstrated By Reduction in Cytogenetically Abnormal Clones and Mutation Burden Leads to Clinical Benefits in Relapsed/Refractory Myelofibrosis Patients
Authors: John Mascarenhas, Rami S. Komrokji, Michele Cavo, Bruno Martino, Dietger Niederwieser, Andreas Reiter, Bart L. Scott, Maria R. Baer, Ronald Hoffman, Olatoyosi Odenike, Laurie Sherman, Souria Dougherty, Faye Feller, Tymara Berry, Libo Sun, Ying Wan, Aleksandra Rizo, Fei Huang, Jean-Jacques Kiladjian
Journal: Blood (2020)
Rituximab Monotherapy Compared to Observation in Patients with Newly Diagnosed Asymptomatic Advanced Stage Follicular Lymphoma: A Retrospective Population-Based Analysis
Authors: Sarah E. Perry, Derrick G. Lee, Ciara L. Freeman, Diego Villa, Alina S. Gerrie, Pedro Farinha, Jeffrey W. Craig, Graham W. Slack, Joseph M. Connors, David W. Scott, Kerry J. Savage, Laurie H. Sehn
Journal: Blood (2020)
A Once Daily, Oral, Triple Combination of BTK Inhibitor, mTOR Inhibitor and IMiD for Treatment of Relapsed/Refractory Richter's Transformation and De Novo Diffuse Large B-Cell Lymphoma
Authors: Anthony R. Mato, Stephen J. Schuster, Francine M. Foss, Iris Isufi, Shalin K. Kothari, Wei Ding, Danielle M. Brander, Andrea Sitlinger, Allison C. Rosenthal, Jose F. Leis, Han W. Tun, Kaitlin Kennard, Allison R. Nelson, Victoria Falco, Celina J. Komari, Amber B. Koehler, Rachel Stowe, Wei He, Albert Kearney, Min Gui, Tim McKinlay, Lindsey E Roeker, Meghan C. Thompson, Scott F. Huntington
Journal: Blood (2020)
SAT0549 SARCOPENIA IN RHEUMATOID ARTHRITIS FEMALE PATIENTS: RELATIONSHIP BETWEEN WHOLE BODY AND TRABECULAR BONE SCORE
Authors: Andrea Casabella, Barbara Ruaro, Chiara Seriolo, Luigi Molfetta, Elisa Alessandri, Carmen Pizzorni, Alberto Sulli, Maurizio Cutolo, Sabrina Paolino
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Rheumatoid arthritis (RA) is associated with muscle loss, osteoporosis and an increased risk of fractures. Sarcopenia is a syndrome in which muscle mass loss is linked to functional loss.Trabecular Bone Score (TBS), is an index extracted from the dual-energy X-ray absorptiometry (DXA) that provides an indirect measurement of bone axial microarchitecture and allows to get information about bone quality [1-3]. <h3>Objectives:</h3> The aims of this study were to examine associations between bone mineral density, bone quality, fat mass and lean mass in the whole body in female patients with RA and healthy controls (CNT). <h3>Methods:</h3> 55 female patients (mean age 58±12 years) affected by RA and 55 CNT (mean age 52±16 years) were enrolled. Bone Mineral Density (BMD, g/cm<sup> 2</sup>) of the lumbar spine (L1-L4) and whole body expressed by Relative skeletal mass index (RSMI) was analyzed using a DXA scan (GE, Lunar Prodigy). Lumbar spine TBS was derived for each spine DXA examination using the TBS index (TBS iNsight Medimaps).For all subject was calculate the Body Mass Index (BMI, kg/m<sup>2</sup>). According to the anthropometric equation [4], sarcopenia was defined as RSMI&lt;5.5 kg/m<sup>2</sup> on women. <h3>Results:</h3> The mean BMD±SD compared by RA and CNT was 0.894±0.127 g/cm<sup>2</sup> vs 1.298±0.672 g/cm<sup>2</sup> at the lumbar spine and 0.694±0.842 g/cm<sup>2</sup> vs 1.132±0.998 g/cm<sup>2</sup> on total hip, respectively, all p&lt;0.001. The mean of BMI and RSMI value in RA patients was lower, 26.1 ± 3.92 kg/m<sup>2</sup> and 5.94 ± 0.42 kg/m<sup>2</sup> respectively, compared by CNT (23.7± 2.98 kg/m<sup>2</sup> and 6.92±0.71 kg/m<sup>2</sup>). Nineteen RA women (35%) presented sarcopenia. Most of RA patients (80%) had bone loss that was significantly lower when compared with control group (p&lt;0.001). Lumbar spine TBS was found significantly lower in RA patients compared with CNT (0.868±0.227 vs 1.482±0.113,p&lt;0.001, respectively). There was not significant correlation between BMI kg/m<sup>2</sup> and RSMI kg/m<sup>2</sup> values. There was a positive correlation between the TBS and RSMI values in RA patients (p=0.002). <h3>Conclusion:</h3> This study show that sarcopenia is frequent in RA patients, mostly on those classified as normal or overweight according to BMI. Therefore TBS and BMD values, as demonstrated could have a key role in a bone-muscle feedback in chronic systemic inflammatory rheumatic diseases, such as RA. <h3>References</h3> [1] Cutolo M et al. Autoimmun Rev 2011:12;84-7 2. Ruaro B, Casabella A, et al. Rheumatology (Oxford). 2018;57:1548-1554. 3.Ruaro B, Casabella A, et al. Rheumatology (Oxford). 2018;57:1548-1554 4. Baumgartner RN et al., J Epidemiol. 147:755–763 <h3>Disclosure of Interests:</h3> None declared
Real World Experience of Etanercept in Steroid Refractory Acute Graft Versus Host Disease from a Tertiary Cancer Centre in India
Authors: Akanksha Chichra, Sachin Punatar, Anant Gokarn, Sumeet Prakash Mirgh, Vijay Shirure, Vinodhini Murugaiyan, Avinash Bonda, Lingaraj Nayak, Bhausaheb Bagal, Sadhana Kannan, Libin J Mathew, Tapan Saikia, Navin Khattry
Journal: Blood (2020)
Outcomes of Allogeneic Hematopoietic Cell Transplantation with Cord Blood Versus Mismatched Unrelated Donor with Post-Transplant Cyclophosphamide in Acute Myeloid Leukemia: An Analysis from the ALWP of the EBMT
Authors: Bhagirathbhai Dholaria, Myriam Labopin, Jaime Sanz Caballer, Annalisa Ruggeri, Jan J. Cornelissen, Hélène Labussière-Wallet, Didier Blaise, Edouard Forcade, Patrice Chevallier, Anna Grassi, Ludmila S Zubarovskaya, Jurgen H.E. Kuball, Patrice Ceballos, Fabio Ciceri, Bipin N. Savani, Arnon Nagler, Mohamad Mohty
Journal: Blood (2020)
SARS-CoV-2 seroprevalence and transmission risk factors among high-risk close contacts: a retrospective cohort study
Authors: Oon Tek Ng, Kalisvar Marimuthu, Vanessa Koh, Junxiong Pang, Kyaw Zaw Linn, Jie Sun, Liang De Wang, Wan Ni Chia, Charles Tiu, Monica Chan, Li Min Ling, Shawn Vasoo, Mohammad Yazid Abdad, Po Ying Chia, Tau Hong Lee, Ray Junhao Lin, Sapna P Sadarangani, Mark I-Cheng Chen, Zubaidah Said, Lalitha Kurupatham, Rachael Pung, Lin-Fa Wang, Alex R Cook, Yee-Sin Leo, Vernon JM Lee
Journal: The Lancet Infectious Diseases (2020)
Optimizing Hydroxyurea Therapy with Reduced Laboratory Monitoring for Children with Sickle Cell Anemia in Sub-Saharan Africa: The Reach Experience
Authors: Banu Aygun, George A. Tomlinson, Patrick T. McGann, Leon Tshilolo, Thomas N. Williams, Peter Olupot-Olupot, Brigida Santos, Susan E. Stuber, Adam Lane, Teresa Latham, Russell E. Ware
Journal: Blood (2020)
AB0038 Rheumatoid arthritis with sacrolitis
Authors: WW Mor¯o£, DK Kapo£ka, UB Brych, AT Tarka, RK Kocur
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> What is the form of rheumatoid arthritis (RA) with asymmetric peripheral arthritis, sacroilitis and present rheumatoid factor (RF). <h3>Objectives</h3> The aim of this work is a presentation rhematoid arhritis considering an illness begining, increase's dynamics of RF and sacroilitis. <h3>Methods</h3> 41 cases of RA sacroilitis and increased RF were retrospectively analysed considering clinical, radiological and laboratory indices. <h3>Results</h3> Monoarthritis appeared as often as not in knee-joints (42%), talus-joints (44%) and single joints of hand (41%). Radiological asymmetry of sacroilitis was found in 27%. there appeared 42% (10) atlantoodontoid subluxations from among 24 X-ray pictures. In 49% of analysed a degree of arthritis changes was twice as advanced in peripheral joints than sacroiliac joints. In 22% the progression of radiological changes correlated with RF Titre. In laboratory research: there was increase dynamics of RF in 51%. In 71% Cases (15 examined) ascertained high circulating immuno complexes. in 26% (38 examined) ascertained increased gamma globulins. Other inflammation parameters were also high. Among accompanied disorders important were: hypertension blood in 51%, cystes of renals in 27% (26 examined). <h3>Conclusion</h3> RA with sacroilitis and present RF is an aggressive and systemic form. It begins tricky with single joints. Progression of destructive changes is most advanced in peripheral joints and cervical vertebral column than sacroiliac joints. Symptomatically often accompany vasculitis and gammapathia.
Early-Life Body Adiposity and the Breast Tumor Transcriptome
Authors: Jun Wang, Cheng Peng, Catherine Guranich, Yujing J Heng, Gabrielle M Baker, Christopher A Rubadue, Kimberly Glass, A Heather Eliassen, Rulla M Tamimi, Kornelia Polyak, Susan Hankinson
Journal: JNCI Journal of the National Cancer Institute (2020)

Cumulative epidemiologic evidence has shown that early-life adiposity is strongly inversely associated with breast cancer risk throughout life, independent of adult obesity. However, the molecular mechanisms remain poorly understood.We assessed the association of early-life adiposity, defined as self-reported body size during ages 10-20 years from a validated 9-level pictogram, with the transcriptome of breast tumor (N = 835) and tumor-adjacent histologically normal tissue (N = 663) in the Nurses' Health Study. We conducted multivariable linear regression analysis to identify differentially expressed genes in tumor and tumor-adjacent tissue, respectively. Molecular pathway analysis using Hallmark gene sets (N = 50) was further performed to gain biological insights. Analysis was stratified by tumor estrogen receptor (ER) protein expression status (n = 673 for ER+ and 162 for ER- tumors).No gene was statistically significantly differentially expressed by early-life body size after multiple comparison adjustment. However, pathway analysis revealed several statistically significantly (false discovery rate < 0.05) upregulated or downregulated gene sets. In stratified analyses by tumor ER status, larger body size during ages 10-20 years was associated with decreased cellular proliferation pathways, including MYC target genes, in both ER+ and ER- tumors. In ER+ tumors, larger body size was also associated with upregulation in genes involved in TNFα/NFkB signaling. In ER- tumors, larger body size was additionally associated with downregulation in genes involved in interferon α and interferon γ immune response and Phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling; the INFγ response pathway was also downregulated in ER- tumor-adjacent tissue, though at borderline statistical significance (false discovery rate = 0.1).These findings provide new insights into the biological and pathological underpinnings of the early-life adiposity and breast cancer association.
Abstract 303: Decreasing Microenvironment Stiffness Improves Exogenous Extracellular Matrix Induced Heart Regeneration in Neonatal Mouse
Authors: Xinming Wang, Samuel Senyo
Journal: Circulation Research (2020)

Introduction: Transplanting cardiac extracellular matrix (ECM) has been demonstrated to influence healing in post-ischemic hearts. We propose that altering mechanical properties can stimulate a regenerative response in ECM-treated hearts. In this study, we investigate the role of mechanical unloading and solubilized ECM to modulate matrix-induced heart regeneration in low-regenerative P5 neonatal mice after acute myocardial infarction and mouse ventricle explants. Methods: P5 neonatal mouse heart stiffness was lowered by inhibiting formation of new collagen crosslinks. Solubilized fetal ECM was injected immediately after myocardial infarction (MI). Heart function and histology were conducted at week 3 post-MI. Cardiac ventricle explants were also used to investigate relevant signaling pathways. Results: We observed that lowering tissue stiffness increased the regenerative influence of fetal ECM treatment on heart function, fibrosis, and cardiomyocyte proliferation. Decrease heart stiffness inhibits fibrosis and better preserves heart function in fetal ECM treated hearts (Figure 1). We further provide evidence that yes-associated protein (Yap) signaling pathway plays a role in ECM-induced cardiomyocyte proliferation possibly through cytoskeleton polymerization.The results suggest that the native microenvironment stiffness, particularly with aging or post-ischemia, affects the therapeutic efficacy of drugs for heart disease. Figure 1 . Fetal ECM treatment P5 mouse hearts showed a higher ejection fraction in comparison with the control hearts at 3-weeks post-MI. Decreasing heart stiffness in P5 mouse heart further promoted increased ejection fraction in fetal ECM treated animals. (n=5, two-way ANOVA test and Tukey’s test, *p&lt;0.05, ****p&lt;0.0001.)
Anti-Myeloma Drug Melflufen Inhibits RANKL-Stimulated Osteoclastogenesis By Suppressing Proliferation of CD14+ Precursor Cells
Authors: Konstantin Byrgazov, Annica Rasmusson, Claes Andersson, Malin Berglund, Lena Lenhammar, Håkan Melhus, Joachim Gullbo, Ana Slipicevic, Fredrik Lehmann, Rolf Larsson, Thomas Lind, Mårten Fryknäs
Journal: Blood (2020)
A Novel CD138-Targeting Monoclonal Antibody Induces Potent Myeloma Killing and Further Synergizes with IMiDs or Bortezomib in in Vitro and In Vivo Preclinical Models of Human Multiple Myeloma
Authors: Tengteng Yu, Bharat Chaganty, Liang Lin, Lijie Xing, Boopathy Ramakrishnan, Kenneth Wen, Phillip A Hsieh, Andrew Wollacott, Karthik Viswanathan, Hedy Adari, Shih-Feng Cho, Yuyin Li, Wenjuan Yang, Hailin Chen, Yan Xu, Gang An, Lugui Qiu, Nikhil C. Munshi, Gregory Babcock, Zach Shriver, James Myette, Kenneth Anderson, Yu-Tzu Tai
Journal: Blood (2020)