tbuckley/cabot-search huggingface dataset:
Deep Phenotyping by Mass Cytometry and Single-Cell RNA-Sequencing Reveals LYN-Regulated Signaling Profiles Underlying Monocyte Subset Heterogeneity and Lifespan
Authors: Morgan E. Roberts, Maunish Barvalia, Jessica A.F.D. Silva, Rachel A. Cederberg, William Chu, Amanda Wong, Daven C. Tai, Sam Chen, Israel Matos, John J. Priatel, Pieter R. Cullis, Kenneth W. Harder
Journal: Circulation Research (2020)

Monocytes are key effectors of the mononuclear phagocyte system, playing critical roles in regulating tissue homeostasis and coordinating inflammatory reactions, including those involved in chronic inflammatory diseases such as atherosclerosis. Monocytes have traditionally been divided into 2 major subsets termed conventional monocytes and patrolling monocytes (pMo) but recent systems immunology approaches have identified marked heterogeneity within these cells, and much of what regulates monocyte population homeostasis remains unknown. We and others have previously identified LYN tyrosine kinase as a key negative regulator of myeloid cell biology; however, LYN's role in regulating specific monocyte subset homeostasis has not been investigated.We sought to comprehensively profile monocytes to elucidate the underlying heterogeneity within monocytes and dissect how Lyn deficiency affects monocyte subset composition, signaling, and gene expression. We further tested the biological significance of these findings in a model of atherosclerosis.Mass cytometric analysis of monocyte subsets and signaling pathway activation patterns in conventional monocytes and pMos revealed distinct baseline signaling profiles and far greater heterogeneity than previously described. Lyn deficiency led to a selective expansion of pMos and alterations in specific signaling pathways within these cells, revealing a critical role for LYN in pMo physiology. LYN's role in regulating pMos was cell-intrinsic and correlated with an increased circulating half-life of Lyn-deficient pMos. Furthermore, single-cell RNA sequencing revealed marked perturbations in the gene expression profiles of Lyn-/- monocytes with upregulation of genes involved in pMo development, survival, and function. Lyn deficiency also led to a significant increase in aorta-associated pMos and protected Ldlr-/- mice from high-fat diet-induced atherosclerosis.Together our data identify LYN as a key regulator of pMo development and a potential therapeutic target in inflammatory diseases regulated by pMos.
INDOXYL SULFATE IS A KEY PLAYER IN THE CARDIORENAL ANEMIA SYNDROME AND PREDICTS THE CLINICAL OUTCOME AFTER ACUTE DECOMPENSATED HEART FAILURE
Authors: Ippei Watanabe, Junko Tatebe, Takahiro Fujii, Hideki Koike, Takanori Ikeda, Toshisuke Morita
Journal: Journal of the American College of Cardiology (2020)
18F-FDG Uptake in a T2 Hypointense Paraspinal Mass
Authors: Aparna Singhal, Narendra Adhikari, Diego A. de Idiaquez Bakula, Houman Sotoudeh
Journal: Clinical Nuclear Medicine (2020)

We present a paraspinal amyloidoma found incidentally in a 77-year-old man during lymphoma workup by F-FDG PET/CT. A solitary FDG-avid paraspinal lesion was seen at T11-T12. MRI showed T2 hypointensity and enhancement. Lymphoma was considered the primary differential due to FDG uptake, but biopsy revealed nodules of extracellular acellular homogeneous material with apple-green birefringence on Congo red stain consistent with amyloidoma. Spinal amyloidoma is rare with few cases reported so far in literature.
PDGFR-β expression in small cell lung cancer patients
Authors: B. Lu
Journal: Journal of Clinical Oncology (2006)

17128 Background: Small cell lung cancer (SCLC) carries an extremely poor prognosis and treatment options for this disease remain poor. PDGF and PDGFR-β are expressed and have been found to have prognostic value in several human cancers. Data in non-small cell cancer cell lines have suggested that PDGFR is a therapeutic target for drug development. In the current study PDGFR-β expression and prognostic value in SCLC was investigated. Methods: Paraffin embedded tissue blocks from 53 patients with limited and extensive stage SCLC were obtained for immunohistochemical staining. Tumors from each patient were sampled three times and stained with PDGFR-β specific antibody. Patients were divided into low and high staining groups based on intensity. Results: There was high intensity PDGFR-β staining in 20 patients with SCLC. Another 29 expressed low intensity PDGFR- β staining, with only 4 patients showing no PDGFR- β staining. There was no statistically significant difference in five year overall survival between patients with low levels of PDGFR-β staining versus those with high level staining SCLC tumors (P = 0.538). Conclusions: Though expression of PDGFR-β may not be a predictor of prognosis, due to its high expression in SCLC it may represent an important target for improved tumor control, however, further studies are required to confirm this. No significant financial relationships to disclose.
Current management of advanced melanoma: A European perspective.
Authors: Clare Frances Jones, Zhongyun Zhao, Beth L. Barber, Marloes Bagijn, Deborah Saltman
Journal: Journal of Clinical Oncology (2013)

9045 Background: Melanoma is a rare but serious subtype of skin cancer that can infiltrate deep skin layers and commonly metastasizes. Although it makes up only a small proportion (&lt;5%) of all skin cancer cases, it causes 75% of deaths from skin cancer. Melanoma affects all ages with 38% of patients less than 55 years old causing significant work productivity and life impact. Median survival of patients with advanced (unresectable or metastatic) melanoma is less than a year. Conventional chemotherapy provides no overall survival benefit. Within the last 2 years, the EMA approved two new drugs for advanced melanoma: ipilimumab for second-line and vemurafenib for patients with BRAF mutation-positive tumors; both drugs provide survival benefits. The objective of this study was to investigate physicians' perceptions of the unmet need in the treatment of advanced melanoma in the new treatment landscape. Methods: 150 oncologists and dermatologists from France, Germany, Italy, Spain, and the UK who had treated at least 12 patients with advanced melanoma in the last 12 months prior to September 2012 were asked by a web-based survey to describe their treatment of advanced melanoma and the current issues in treatment. Results: Overall, 76% of respondents had used ipilimumab and 79% had used vemurafenib in the 12 months prior to September 2012. Toxicity and tolerability of treatment was the most commonly mentioned issue (cited by 43% of respondents). Limited treatment effectiveness (29% respondents) was also highlighted by respondents in all countries. Limited treatment options were identified as a key issue by 30% of respondents in Germany, France, and the UK. Other commonly mentioned issues were low response rates and poor survival. Conclusions: The majority of physicians surveyed had experience using vemurafenib and ipilimumab. However, a number of issues remain in the treatment of advanced melanoma, suggesting that unmet need remains high.
UTILITY OF TROPONIN I AND CARDIAC MAGNETIC RESONANCE IN THE ASSESSMENT OF CARDIAC INVOLVEMENT IN IDIOPATHYC INFLAMMATORY MYOSITIS
Authors: Georgiana Luisa Baca, Mark Dawkins, Oliver Guttmann, Rajiv Amersey, Shanti Velmurugan, Stefania Rosmini
Journal: Journal of the American College of Cardiology (2020)
Measuring chemotherapy safety in a community oncology practice: Results of a three-year prospective study
Authors: J. O. Jacobson, M. K. Krzyzanowska, J. H. Schwartz, B. Maloney, A. Lavino, J. Treacy
Journal: Journal of Clinical Oncology (2006)

6019 Background: Chemotherapy administration is associated with a risk for severe toxicity and mortality. Limited data are available to assess these risks outside of clinical trials or administrative databases. We sought to determine the risk of chemotherapy administration in a community-based oncology practice, to identify potential risk factors, and to look for trends over time. Methods: The North Shore Medical Center Cancer Center (NSCC) is a community-based cancer facility in Peabody, MA. In 1/03, we began a prospective study to identify and categorize all adult patients admitted to hospital with severe chemotherapy toxicity and to compare them to all chemotherapy recipients. Consecutive cases admitted to hospital from NSCC were reviewed in a monthly multidisciplinary peer review meeting. Admissions deemed to be treatment-related were entered into a toxicity database. Results: Between 1/1/03 and 11/30/05, 2206 courses of chemotherapy were administered to 1574 patients resulting in 12,380 treatment-months of therapy. 162 patients required 174 hospital admissions, for an annualized risk of treatment-related hospitalization (TRH) of 16.6% and a mean length of stay of 7.0 days. Mean age of cases was similar for those admitted for toxicity compared to all chemotherapy patients (65.3 versus 64.6 yrs.). GI toxicity and infection (principally fever and neutropenia) accounted for 77% of TRH. Between 2003 and 2005, the risk of a TRH declined for colorectal cancer cases while it increased for breast cancer and lung cancer cases. There were 14 treatment-related deaths (TRD) for an annualized risk of 1.1%. TRD’s were infectious in 9, GI in 4 and cardiac in 1. Median age was 67, similar to the entire cohort. TRD occurred early (median 28 days from the inception of chemotherapy, range 1–120 days). Significant comorbidity was identifiable in 12 of 14 cases. 10 of 14 cases were being treated palliatively. Conclusions: These prospectively collected data confirm that chemotherapy administration in a community-based practice can be associated with a low risk of severe toxicity and a very low risk of mortality. TRH and TRD could become standard measures of quality care for cancer facilities. No significant financial relationships to disclose.
POSTOPERATIVE TROPONIN ELEVATION IN NON-CARDIAC SURGERY PRESENTS AN OPPORTUNITY TO RE-STRATIFY PREOPERATIVELY LOW-RISK PATIENTS TOWARD ACTIONABLE PREVENTION STRATEGIES
Authors: Enrique Soltero Mariscal, Sunil Vasireddi, Erica Pivato, Meera Devi Kondapaneni, Douglas Gunzler, Peter Leo
Journal: Journal of the American College of Cardiology (2020)
Impact of copayment elimination on annual and biennial screening mammography utilization among rural U.S. women.
Authors: Jeffrey M. Peppercorn, Stephanie B. Wheeler, Kevin Houck, Bercedis Peterson, Victor Villagra, James Antetomaso, Adane Fekadu Wogu, Gary H. Lyman
Journal: Journal of Clinical Oncology (2013)

6503 Background: Early detection of breast cancer through mammography screening leads to earlier stage at diagnosis and improved survival. Previous research has shown that rural American women are less likely to receive screening mammography compared to their urban counterparts. Copayments for mammography are a potential barrier to screening, and elimination of copayments may improve screening rates. We examined annual (aSMU) and biennial (bSMU) screening mammography utilization and the impact of copayment elimination among rural U.S. women. Methods: Using the insurance claims database of the National Rural Electric Cooperative Association (NRECA), which insures over 100,000 electrical workers and their families nationally, we identified all women ages 40 to 64 with no prior history of invasive breast cancer or DCIS (based on ICD-9 codes) and captured claims for aSMU and bSMU between 1999 and 2009. Changes in screening over time were assessed for the periods before and after NRECA elimination of copayments for screening mammography in January, 2006. Chi-squared tests were used to compare aSMU and bSMU rates by age group. All p-values are two-sided. Results: During this time period, over 20,000 women ages 40 to 64 received health insurance through NRECA each year. From 1999 to 2009, aSMU increased from 38.1% to 49.5%, while bSMU increased from 57.2% to 68.1%. Screening increased significantly following elimination of copayments in 2006 (p = 0.0004). Specifically, for the period 2006-2007 compared to 2004-2005, the percentage of women undergoing at least biennial screening increased from 60.9 to 68.8% (p &lt; 0.0001), with absolute differences in screening by age ranging from an increase of 5.3% among women 40-45, to 10% among women 60 – 64. Conclusions: Evaluation of insurance claims data from rural US populations reveals that a large percentage of rural women ages 40 to 64 do not undergo even biennial breast cancer screening. Elimination of copayments improves both annual and biennial screening rates in all age groups, but does not eliminate all barriers. Further investigation is ongoing to understand financial and non-financial barriers to screening and attitudes towards current screening recommendations.
Abstract 14913: Variable Effects on Lipid Transporting and Non-Lipid Transporting Functions of HDL in Young Patients With Chronic Inflammatory Arthritis
Authors: Preethi Mani, Kiyoko Uno, MyNgan Duong, Kathy Wolski, Steven Spalding, Elaine Husni, Stephen Nicholls
Journal: Circulation (2013)

Background: Impaired high density lipoprotein (HDL) functionality may contribute to increased cardiovascular risk in adults with chronic inflammatory disorders. It has not been established if early...
Sexual and Gender Minority Curricula Within US Dermatology Residency Programs
Authors: Justin L. Jia, Kristin M. Nord, Kavita Y. Sarin, Eleni Linos, Elizabeth E. Bailey
Journal: JAMA Dermatology (2020)

Sexual and gender minority (SGM) patients face many health challenges, including higher burdens of skin cancer, sexually transmitted diseases, and complications associated with hormone therapy or gender-affirming surgery. 1 Improving clinician knowledge of SGM patients' health needs may improve quality of care for this population. 2The goal of this study was to assess what SGMspecific health topics are covered in dermatology residency programs to identify possible gaps and guide improvements.Methods | In August 2018, a web-based survey (eAppendix in the Supplement) was sent to the 123 US dermatology residency programs represented by the Association of Professors of Dermatology listserv (electronic mailing list), requesting 1 response per program.The survey was adapted from surveys used to assess SGM residency curricula in other medical specialties 3,4 and included questions about residency demographic characteristics, integration of SGM content, importance of SGM-specific training, barriers to integration, and opinions on best ways to incorporate SGM-specific topics.
Dendritic Cell Paucity Leads to Dysfunctional Immune Surveillance in Pancreatic Cancer
Authors: Samarth Hegde, Varintra E. Krisnawan, Brett H. Herzog, Chong Zuo, Marcus A. Breden, Brett L. Knolhoff, Graham D. Hogg, Jack P. Tang, John M. Baer, Cedric Mpoy, Kyung Bae Lee, Katherine A. Alexander, Buck E. Rogers, Kenneth M. Murphy, William G. Hawkins, Ryan C. Fields, Carl J. DeSelm, Julie K. Schwarz, David G. DeNardo
Journal: Cancer Cell (2020)
Rb and p53-Deficient Myxofibrosarcoma and Undifferentiated Pleomorphic Sarcoma Require Skp2 for Survival
Authors: George Z. Li, Tomoyo Okada, Young-Mi Kim, Narasimhan P. Agaram, Francisco Sanchez-Vega, Yawei Shen, Norifumi Tsubokawa, Jordan Rios, Axel S. Martin, Mark A. Dickson, Li-Xuan Qin, Nicholas D. Socci, Samuel Singer
Journal: Cancer Research (2020)

Abstract Myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS) are highly genetically complex soft tissue sarcomas. Up to 50% of patients develop distant metastases, but current systemic therapies have limited efficacy. MFS and UPS have recently been shown to commonly harbor copy number alterations or mutations in the tumor suppressor genes RB1 and TP53. As these alterations have been shown to engender dependence on the oncogenic protein Skp2 for survival of transformed cells in mouse models, we sought to examine its function and potential as a therapeutic target in MFS/UPS. Comparative genomic hybridization and next-generation sequencing confirmed that a significant fraction of MFS and UPS patient samples (n = 94) harbor chromosomal deletions and/or loss-of-function mutations in RB1 and TP53 (88% carry alterations in at least one gene; 60% carry alterations in both). Tissue microarray analysis identified a correlation between absent Rb and p53 expression and positive expression of Skp2. Downregulation of Skp2 or treatment with the Skp2-specific inhibitor C1 revealed that Skp2 drives proliferation of patient-derived MFS/UPS cell lines deficient in both Rb and p53 by degrading p21 and p27. Inhibition of Skp2 using the neddylation-activating enzyme inhibitor pevonedistat decreased growth of Rb/p53-negative patient-derived cell lines and mouse xenografts. These results demonstrate that loss of both Rb and p53 renders MFS and UPS dependent on Skp2, which can be therapeutically exploited and could provide the basis for promising novel systemic therapies for MFS and UPS. Significance: Loss of both Rb and p53 renders myxofibrosarcoma and undifferentiated pleomorphic sarcoma dependent on Skp2, which could provide the basis for promising novel systemic therapies. See related commentary by Lambert and Jones, p. 2437
Optimal, resource-rational or sub-optimal? Insights from cognitive development
Authors: Vikranth R. Bejjanki, Richard N. Aslin
Journal: Behavioral and Brain Sciences (2020)

Abstract We agree with the authors regarding the utility of viewing cognition as resulting from an optimal use of limited resources. Here, we advocate for extending this approach to the study of cognitive development, which we feel provides particularly powerful insight into the debate between bounded optimality and true sub-optimality, precisely because young children have limited computational and cognitive resources.
Trib1 regulates T cell differentiation during chronic infection by restraining the effector program
Authors: Kelly S. Rome, Sarah J. Stein, Makoto Kurachi, Jelena Petrovic, Gregory W. Schwartz, Ethan A. Mack, Sacha Uljon, Winona W. Wu, Anne G. DeHart, Susan E. McClory, Lanwei Xu, Phyllis A. Gimotty, Stephen C. Blacklow, Robert B. Faryabi, E. John Wherry, Martha S. Jordan, Warren S. Pear
Journal: The Journal of Experimental Medicine (2020)

In chronic infections, the immune response fails to control virus, leading to persistent antigen stimulation and the progressive development of T cell exhaustion. T cell effector differentiation is poorly understood in the context of exhaustion, but targeting effector programs may provide new strategies for reinvigorating T cell function. We identified Tribbles pseudokinase 1 (Trib1) as a central regulator of antiviral T cell immunity, where loss of Trib1 led to a sustained enrichment of effector-like KLRG1+ T cells, enhanced function, and improved viral control. Single-cell profiling revealed that Trib1 restrains a population of KLRG1+ effector CD8 T cells that is transcriptionally distinct from exhausted cells. Mechanistically, we identified an interaction between Trib1 and the T cell receptor (TCR) signaling activator, MALT1, which disrupted MALT1 signaling complexes. These data identify Trib1 as a negative regulator of TCR signaling and downstream function, and reveal a link between Trib1 and effector versus exhausted T cell differentiation that can be targeted to improve antiviral immunity.
THE IMPACT OF ROUTINE CARDIOLOGY CONSULTATION ON CRITICALLY ILL PATIENTS WITH ELEVATED TROPONIN LEVELS
Authors: Omar Kousa, Amr Essa, Muhammad Ahsan, Venkata Siva Kumar Pajjuru, Abedelrahman Anani, Mohammed Saleh, Aiza Ahmad, Janani Baskaran, Yaman Alali, Ryan Walters, Toufik Mahfood Haddad, Aiman Miloud Smer
Journal: Journal of the American College of Cardiology (2020)
Comprehensive pharmacogenomic characterization of gastric cancer
Authors: Jason K. Sa, Jung Yong Hong, In-Kyoung Lee, Ju-sun Kim, Moon-Hee Sim, Ha Jung Kim, Ji Yeong An, Tae Sung Sohn, Joon Ho Lee, Jae Moon Bae, Sung Kim, Kyoung-Mee Kim, Seung Tae Kim, Se Hoon Park, Joon Oh Park, Ho Yeong Lim, Won Ki Kang, Nam-Gu Her, Yeri Lee, Hee Jin Cho, Yong Jae Shin, Misuk Kim, Harim Koo, Mirinae Kim, Yun Jee Seo, Ja Yeon Kim, Min-Gew Choi, Do-Hyun Nam, Jeeyun Lee
Journal: Genome Medicine (2020)

Abstract Background Gastric cancer is among the most lethal human malignancies. Previous studies have identified molecular aberrations that constitute dynamic biological networks and genomic complexities of gastric tumors. However, the clinical translation of molecular-guided targeted therapy is hampered by challenges. Notably, solid tumors often harbor multiple genetic alterations, complicating the development of effective treatments. Methods To address such challenges, we established a comprehensive dataset of molecularly annotated patient derivatives coupled with pharmacological profiles for 60 targeted agents to explore dynamic pharmacogenomic interactions in gastric cancers. Results We identified lineage-specific drug sensitivities based on histopathological and molecular subclassification, including substantial sensitivities toward VEGFR and EGFR inhibition therapies in diffuse- and signet ring-type gastric tumors, respectively. We identified potential therapeutic opportunities for WNT pathway inhibitors in ALK -mutant tumors, a significant association between PIK3CA- E542K mutation and AZD5363 response, and transcriptome expression of RNF11 as a potential predictor of response to gefitinib. Conclusions Collectively, our results demonstrate the feasibility of drug screening combined with tumor molecular characterization to facilitate personalized therapeutic regimens for gastric tumors.
ESO–ESMO 4th International Consensus Guidelines for Breast Cancer in Young Women (BCY4)
Authors: S. Paluch-Shimon, F. Cardoso, A.H. Partridge, O. Abulkhair, H.A. Azim, G. Bianchi-Micheli, M.-J. Cardoso, G. Curigliano, K.A. Gelmon, N. Harbeck, J. Merschdorf, P. Poortmans, G. Pruneri, E. Senkus, T. Spanic, V. Stearns, Y. Wengström, F. Peccatori, O. Pagani
Journal: Annals of Oncology (2020)
EFFECTIVENESS AND SAFETY OF COMBINATION THERAPY WITH AMBRISENTAN AND TADALAFIL FOR THE TREATMENT OF PULMONARY ARTERIAL HYPERTENSION IN CHILDREN
Authors: Azadeh Issapour, Sarah Crook, Michelle Hite, Erika Berman Rosenzweig, Benjamin Frank, Dunbar Ivy, Usha Krishnan
Journal: Journal of the American College of Cardiology (2020)
OMTX705, a Novel FAP-Targeting ADC Demonstrates Activity in Chemotherapy and Pembrolizumab-Resistant Solid Tumor Models
Authors: Myriam Fabre, Cristina Ferrer, Saioa Domínguez-Hormaetxe, Bruno Bockorny, Laura Murias, Oliver Seifert, Stephan A. Eisler, Roland E. Kontermann, Klaus Pfizenmaier, So Young Lee, María dM. Vivanco, Pedro P. López-Casas, Sofia Perea, Muhammad Abbas, Wolfgang Richter, Laureano Simon, Manuel Hidalgo
Journal: Clinical Cancer Research (2020)

The tumor microenvironment plays a key role in cancer development and progression and is involved in resistance to chemo- and immunotherapy. Cancer-associated fibroblast expressing fibroblast-activating protein α (FAPα) is one of the predominant stroma cell types and is involved in resistance to immunotherapy.We generated OMTX705, a novel antibody-drug conjugate from a humanized anti-FAP antibody linked to a new cytolysin. Here, we studied its antineoplastic activity in vitro and in preclinical mouse models alone and in combination with chemotherapy as well as immunotherapy in PD-1-resistant tumors.In Avatar models, OMTX705 showed a 100% tumor growth inhibition and prolonged tumor regressions as single agent and in combination with chemotherapy. Treatment rechallenge following treatment discontinuation induced additional tumor regression, suggesting lack of treatment resistance. In a mouse model with a humanized immune system resistant to PD-1 inhibition, OMTX705 increased tumor infiltration by CD8+ T cells, induced complete regressions, and delayed tumor recurrence.These data suggest that FAP targeting with OMTX705 represents a novel and potent strategy for cancer treatment, including tumors resistant to immunotherapy, and support its clinical development.