bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PO-069: SRMS correlated with immune infiltration and lung cancer: Allusion for COVID-19
Authors: Swarna Beesetti , Wang Yong-Dong , Potts Malia B. 
Published: December 2020

Abstract
Background: The non-receptor tyrosine kinase, SRMS (Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristoylation sites) is a member of the BRK family kinases (BFKs) that represents an evolutionarily conserved relative of the Src family kinases (SFKs) and is shown to restrain autophagy in mammalian cells. Gene enrichment analyses using the Ingenuity Pathway analyses (IPA) of SRMS interacting partners predicted viral infection as a significantly increased cellular processes. However, the correlation between SRMS and prognosis in LUAD (lung adenocarcinoma) and LUSC (lung squamous cell carcinoma) or its impact on COVID-19 is understudied.
Methods: We analyzed the expression levels of SRMS, and the correlation between SRMS and immune infiltration level in LUAD and LUSC was investigated using TIMER database. Open Target platform was used to analyze the association of SRMS with disease. In addition, we used GSE30589 databases to elucidate the changes of SRMS expression in vitro after SARS-CoV infection in Vero E6 and MA-104 cells.
Results: SRMS was elevated in LUAD and LUSC compared to normal tissues. The expression of SRMS was negatively correlated with the level of immune infiltration of CD8+T cells in LUAD and LUSC. We found that the expression of SRMS increased in vitro after SARS-CoV infection in Vero E6 and MA-104 cells.
Conclusion: SRMS expression increased significantly in LUAD and LUSC, and this elevated SRMS was negatively correlated with immune infiltration at tumors. SARS-CoV infection increased the SRMS expression. This suggests that patients with LUAD and LUSC may be more susceptible to SARS-CoV-2 due to increased SRMS levels that inhibit autophagy and alter tumor microenvironment correlated with reduced immune infiltration, which in turn may worsen the prognoses of LUAD and LUSC patients after SARS-CoV-2 infection.
Citation Format: Beesetti Swarna, Yong-Dong Wang, Malia B. Potts. SRMS correlated with immune infiltration and lung cancer: Allusion for COVID-19 [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-069.
Abstract PO-077: Use of aromatase inhibitors and risk of cardiovascular disease: A population-based study
Authors: McVicker Lauren , Cardwell Christopher , McMenamin Úna 
Published: December 2020

Abstract
Background: Adjuvant endocrine therapy, including aromatase inhibitors (AI) or tamoxifen, is recommended for women diagnosed with estrogen receptor- and/or progesterone receptor-positive breast cancer as it significantly reduces the risk of recurrence and breast cancer-specific mortality. AIs are the preferred treatment for postmenopausal women; however, concerns have been raised with respect to their cardiovascular safety. Some meta-analyses of randomized controlled trials report an increase in cardiovascular disease (CVD) risk with use of AIs compared to tamoxifen; however, “real-world” observational studies have yielded inconsistent findings.
Objectives: We aimed to conduct a population-based study in Scotland to investigate whether breast cancer patients treated with AIs are at an increased risk of cardiovascular disease compared to patients treated with tamoxifen.
Methods: Women newly diagnosed with breast cancer, from 2009 to 2017, were identified from the Scottish Cancer Registry. AI and tamoxifen use were identified from the nationwide Scottish Prescribing Information System. The primary outcome was CVD, based on incidence or death from CVD obtained from hospital admission and death records, respectively. Cox regression models calculated hazard ratios (HRs) and 95% intervals (CIs) comparing AI use to tamoxifen use and risk of CVD, using an as treated exposure definition. Analyses were adjusted for a range of potential confounders and subgroup analysis investigated risk by CVD subtypes including myocardial infarction, heart failure, ischemic stroke, venous thromboembolism, and angina.
Results: The cohort contained 28,712 breast cancer patients, followed for 110,999 person years, during which there were 776 cardiovascular events. Compared to tamoxifen use, AI use was associated with an increased risk of any CVD event (adjusted HR 1.14, 95% CI: 1.02, 1.27), which was particularly marked for ischemic stroke (adjusted HR 1.27, 95% CI: 0.99, 1.63). There were no clear associations for other CVD subtypes.
Conclusions: Our preliminary results suggest an increased risk of CVD, and specifically ischemic stroke, in AI users compared to tamoxifen. Additional analyses will be conducted to further investigate these associations, including dose-response.
Citation Format: Lauren McVicker, Christopher Cardwell, Úna McMenamin. Use of aromatase inhibitors and risk of cardiovascular disease: A population-based study [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-077.
Abstract PO-089: The impact of Covid-19 on public generosity toward cancer-related crowdfunding efforts
Authors: Fischer Katrina A. , Miller Robert E. , Anand Sidharth , Glaspy John 
Published: December 2020

Abstract
Background: Many patients with cancer rely on public crowdfunding platforms to generate financial support toward costs associated with their medical care. It is unclear how financial uncertainties resulting from the Covid-19 pandemic may impact patient need and public support toward routine cancer-focused campaigns.
Methods: Using custom code for web scraping, we identified all campaigns that were generated on the crowdfunding platform GoFundMe.com in the “Medical, Illness and Healing” category between 8/17/2019 and 5/8/2020. This date represents six months of fundraising prior to the first official shelter-in-place order on 3/17/2020. We then abstracted campaigns that included the word “cancer,” originated in the United States, and had raised at least one dollar. Of these cancer-related campaigns, we collected the dollar amount raised in the first 30 days of campaign generation and the total raised to date. Campaigns generated between 2/17/2020 and 3/16/2020 were not included in pre/post-Covid calculations because these campaigns would potentially include contributions made after 3/17/2020 within their first 30-day values.
Results: 19,669 cancer campaigns were identified during the study period (16,823 between 8/17/19 and 2/17/20 and 2,846 between 3/17/20 and 5/8/20), raising on average 83% of total funds within the first 30 days of campaign generation. In the six months prior to the first shelter-in-place order (8/17/19-2/17/20), there were on average 91 new cancer campaigns generated daily. Within the first 30 days, these campaigns averaged $4,472 (median $1,815). After 3/17/20, an average of 54 campaigns were generated daily, representing a 40% decline in daily campaign generation. Within the first 30 days, these campaigns averaged $6,130 (median $2,950), representing a 36% and 60% increase from baseline respectively.
Conclusion: Public generosity has increased toward cancer fundraising campaigns since the Covid-19 pandemic, but fewer patients are creating new campaigns. Patients can be reassured that they will likely continue to benefit from public support and should not feel limited in asking for help during this period of economic uncertainty. As philanthropy sometimes increases during disaster periods, it is unclear if continued support will persist as longer-term economic changes take effect.
Citation Format: Katrina A. Fischer, Robert E. Miller, Sidharth Anand, John Glaspy. The impact of Covid-19 on public generosity toward cancer-related crowdfunding efforts [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-089.
Abstract S03-01: Pan-HLA prediction of SARS-CoV-2 epitopes
Authors: Campbell Katie M. , Steiner Gabriela , Wells Daniel K. , Ribas Antoni , Kalbasi Anusha 
Published: December 2020

Abstract
Introduction: Delineating antiviral T-cell responses to SARS-CoV-2 may shed light on the heterogeneity of clinical outcomes and inform vaccine or therapeutic approaches. Viral antigens can be predicted using computational tools that calculate the binding affinity between viral peptides and antigen presentation machinery. However, in order to account for the role of host genetics in the diversity of responses, this analysis must be performed with consideration of the global diversity of the human leukocyte antigen (HLA) proteins responsible for antigen presentation.
Methods: We deployed binding predictions across the SARS-CoV-2 peptidome for 9,360 Class I HLA alleles (2,987 HLA-A; 3,707 HLA-B; 2,666 HLA-C; 9-mers) using a consensus approach of 7 algorithms and 3,486 Class II HLA alleles (15-mers) using a consensus approach of 4 algorithms. All pMHC predictions were filtered to include only those with consensus binding less than 500 nM.
Results: There were 368,145 unique combinations of peptides and HLA alleles (pMHCs) with a predicted binding affinity of less than 500nM, including 1,103 unique 9-mer and 2,547 15-mer peptides and 1,022 MHC Class I and 8,075 MHC Class II HLA proteins. Of these pMHCs, 82% of 9-mers overlapped with 15-mers, suggesting cross-presentation to both CD4 and CD8 T cells in a subset of individuals. We evaluated this filtered dataset with respect to the population frequency of HLA haplotypes. While the predicted susceptibility of SARS-CoV-2 antigen presentation differed greatly across countries, there was a subset of 21 Class I antigens shared by common HLA types across 30 or more countries (out of 79 countries with reported population frequency data). Our database has been made publicly available, and we have developed a user interface to explore the results based upon viral proteins, HLA alleles, or country populations of interest.
Conclusions: With the ongoing SARS-CoV-2 pandemic, there are worldwide efforts to generate a successful vaccine and to evaluate clinical samples to understand the viral pathogenesis and diverse outcomes in patients. This application can serve as a guide to identify responses of putative SARS-CoV-2-specific T cells across patients with a broad range of HLA haplotypes internationally.
Citation Format: Katie M. Campbell, Gabriela Steiner, Daniel K. Wells, Antoni Ribas, Anusha Kalbasi. Pan-HLA prediction of SARS-CoV-2 epitopes [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr S03-01.
Abstract S07-03: Scientia potentia est: How the Italian world of oncology changes in the COVID19 pandemic
Authors: Ballatore Zelmira , Bastianelli Lucia , Merloni Filippo , Ranallo Nicoletta , Cantini Luca , Mariotti Lorenzo , Catani Claudia , Burattini Michela , Lucarelli Alessandra , Berardi Rossana 
Published: December 2020

Abstract
Background: After COVID-19 was declared a pandemic by the World Health Organization, a response from the Italian Health System to react to an unprecedented condition became necessary and sudden. COVID- 19 pandemic required oncologists to redefine clinical organization and management of cancer patients. The aim of our study was to take a picture of the situation of Italian oncologies and to evaluate the difficulties in patients’ management.
Methods: Between 18th March and 9th April 2020 we conducted an online survey (Google Forms). It consisted of 45 questions ranging from individual perception of pandemic management by oncologic centers to physicians’ and nurses’ psychological distress and patient care. The survey was anonymous and broadcast to oncology health workers by mailing contacts, word of mouth, and social networks.
Results: A total of 383 oncology health workers participated in the survey. The majority was female (72%) and from central Italy (46%). Impressively, a total of 357 (93%) participants declared the Oncologic Department reorganized routine clinical activity, but only 41% were adequately trained about the required procedures. 20% of the survey attendees thought they had not received adequate and timely protective devices with respect to clinical needs, and according to 58% the supply of these devices was only partial. 34% of professionals declared that they did not have or know a defined common guideline to reschedule patients’ treatments. More than 80% of interviewees declared feeling worried about being at greater risk of contagion than the general population, and 92% feared to transmit virus to family members. Deferring treatments has caused fear/anxiety in 228 of the interviewed (60%). Symptoms of stressful situations emerged with a deterioration in sleep quality in 62% of professionals, worsening of mood (69%), and lower concentration ability (49%).
Conclusions: Our survey demonstrated the flexibility of oncologic teams. However, the emergency response quality has been heterogeneous, and several drawbacks emerged from this first analysis. Information, protection, testing, and training of health care professionals are keywords that should be kept in mind to encourage recovery after this tragedy and to be ready to face a similar emergency in the near future.
Citation Format: Zelmira Ballatore, Lucia Bastianelli, Filippo Merloni, Nicoletta Ranallo, Luca Cantini, Lorenzo Mariotti, Claudia Catani, Michela Burattini, Alessandra Lucarelli, Rossana Berardi. Scientia potentia est: How the Italian world of oncology changes in the COVID19 pandemic [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr S07-03.
Abstract S12-02: Risk of morbidity and mortality in COVID-19 patients with cancer
Authors: Alpert Naomi , Marcellino Bridget , Rapp Joseph , Lieberman-Cribbin Wil , Taioli Emanuela 
Published: December 2020

Abstract
Introduction: Morbidity and mortality of cancer patients with COVID-19 have not been examined. The goal of this analysis was to compare the demographics and clinical characteristics of COVID-19 cancer patients to the rest of COVID-19 patients and assess whether cancer is associated with morbidity or mortality.
Methods: COVID-19-positive patients with an inpatient or emergency encounter at the Mount Sinai Health System between 03/01/20-05/27/20 were included in the analysis. Patients were compared across cancer status (noncancer, non-solid cancers, and solid cancers) on demographics and clinical characteristics. Multivariable logistic regressions were used to model the associations of cancer status with sepsis, acute venous thromboembolism, and mortality.
Results: There were 5,516 COVID-19 positive patients included, 96 (1.7%) with non-solid cancers and 325 (5.8%) with solid cancers. Those with solid cancers were significantly older (mean: 70.9 vs. 63.8 and 63.2 years) and more likely to be non-Hispanic Black (26.5% vs. 23.9% and 22.9%) than noncancer and non-solid cancers patients. Those with cancer had significantly more additional comorbid conditions (42.7% and 49.8% ≥2 comorbidities for non-solid and solid cancers, vs. 30.4% for noncancer). Platelets (mean [noncancer]: 223.8, mean [non-solid cancer]: 182.6, mean [solid cancer]: 218.3 × 103/μL), white blood cell count (mean [noncancer]: 8.4, mean [non-solid cancer]: 6.7, mean [solid cancer]: 8.0 × 103/μL), hemoglobin (mean [noncancer]: 13.1, mean [non-solid cancer]: 11.2, mean [solid cancer]: 12.0 g/dL), and red blood cell count (mean [non-cancer]: 4.5, mean [non-solid cancer]: 3.7, mean [solid cancer]: 4.1 × 106/μL) were significantly lower in cancer patients, and lowest in those with non-solid cancers. After adjustment and compared to noncancer patients, those with cancer had significantly higher risk of acute venous thromboembolism (ORadj: 1.77, 95% CI: 1.01-3.09) and sepsis (ORadj: 1.34, 95% CI: 1.09-1.64). There was no significant difference in mortality (ORadj: 1.02, 95% CI: 0.81-1.29). There was no significant difference in all outcomes for solid and non-solid cancer types.
Conclusion: COVID-19 patients with cancer, particularly solid tumors, are significantly older, with more comorbidities than those without cancer. There was no statistically significant difference in mortality for COVID-19 patients with cancer, but a significantly higher risk of thromboembolism and sepsis. Further research into the effect that cancer treatments may have in inflammatory and immune responses to COVID is warranted.
Citation Format: Naomi Alpert, Bridget Marcellino, Joseph Rapp, Wil Lieberman-Cribbin, Emanuela Taioli. Risk of morbidity and mortality in COVID-19 patients with cancer [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr S12-02.
Abstract PO-19: Sequential inverse dysregulation of the RNA helicases DDX3X and DDX3Y facilitates MYC-driven lymphomagenesis
Authors: Gong Chun , Krupka Joanna A. , Gao Jane , Grigoropoulos Nicholas F. , Cucco Francesco , Barrans Sharon , Igor De Los Mozos , Peixun Zhou , Sorca Forde , Jamie Matthews , Amos Burke , Kwan Sze Siu , Philip Beer , Cathy Burton , Peter Campbell , Vikki Rand , Suzanne Turner , Jernej Ule , Eve Roman , Reuben Tooze , Thomas Oellerich , Ming Du , Shamith Samarajiwa , Hodson Daniel J. 
Published: December 2020

Abstract
DDX3X is a ubiquitously expressed RNA helicase involved in multiple stages of RNA biogenesis. DDX3X is frequently mutated in Burkitt lymphoma, but the functional basis for this is unknown. Here, we show that loss-of-function DDX3X mutations are also commonly found in MYC-translocated diffuse large B-cell lymphoma. We reveal functional cooperation between mutant DDX3X and MYC in ex vivo cultured human germinal center B cells. By integrating results of iCLIP, ribosome profiling, and proteomics, we show WT DDX3X promotes the translation of mRNAs encoding components of the core translational machinery, thereby driving global protein synthesis. Loss-of-function DDX3X mutations act to buffer the effect of abrupt MYC expression and moderate MYC-driven global protein synthesis, thereby buffering MYC-induced proteotoxic stress during early lymphomagenesis. Established lymphoma cells subsequently restore full protein synthetic capacity by aberrant expression of DDX3Y, a Y-chromosome homologue that is normally expressed exclusively in testis. These findings show how sequential dysregulation of DDX3X and DDX3Y acts to titrate global protein synthesis to suit the stage-specific needs of developing lymphoma cells and identify DDX3Y as an attractive, male-specific therapeutic target absent from normal human B cells but required for the survival of male lymphomas.
Citation Format: Chun Gong, Joanna A. Krupka, Jane Gao, Nicholas F. Grigoropoulos, Francesco Cucco, Sharon Barrans, De Los Mozos Igor, Zhou Peixun, Forde Sorca, Matthews Jamie, Burke Amos, Sze Siu Kwan, Beer Philip, Burton Cathy, Campbell Peter, Rand Vikki, Turner Suzanne, Ule Jernej, Roman Eve, Tooze Reuben, Oellerich Thomas, Du Ming, Samarajiwa Shamith, Daniel J. Hodson. Sequential inverse dysregulation of the RNA helicases DDX3X and DDX3Y facilitates MYC-driven lymphomagenesis [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr PO-19.
Abstract PO-42: TBL1XR1 mutations drive extranodal lymphomagenesis by inducing a protumorigenic memory B-cell fate
Authors: Venturutti Leandro , Teater Matt , Zhai Andrew , Chadburn Amy , Babiker Leena , Kim Daleum , Staudt Louis , Green Michael , Farinha Pedro , Weng Andrew , Steidl Christian , Morin Ryan , Scott David , Privé Gil , Melnick Ari 
Published: December 2020

Abstract
The most aggressive B-cell lymphomas frequently manifest extranodal distribution and carry somatic mutations in the poorly characterized gene TBL1XR1. Here, we show that TBL1XR1 mutations skew the humoral immune response towards generating abnormal immature memory B-cells (MB), while impairing plasma cell differentiation. At the molecular level, TBL1XR1 mutants co-opt SMRT/HDAC3 repressor complexes towards binding the MB cell transcription factor (TF) BACH2, at the expense of the germinal center (GC) TF BCL6, leading to pre-memory transcriptional reprogramming and cell-fate bias. Upon antigen recall, TBL1XR1 mutant MB cells fail to differentiate into plasma cells and instead preferentially reenter new GC reactions, providing evidence for a cyclic re-entry lymphomagenesis mechanism. Ultimately, TBL1XR1 alterations lead to a striking extranodal immunoblastic lymphoma phenotype that mimics the human disease. Both human and murine lymphomas feature expanded MB-like cell populations, consistent with a MB-cell origin and delineating an unforeseen pathway for malignant transformation of the immune system.
Citation Format: Leandro Venturutti, Matt Teater, Andrew Zhai, Amy Chadburn, Leena Babiker, Daleum Kim, Louis Staudt, Michael Green, Pedro Farinha, Andrew Weng, Christian Steidl, Ryan Morin, David Scott, Gil Privé, Ari Melnick. TBL1XR1 mutations drive extranodal lymphomagenesis by inducing a protumorigenic memory B-cell fate [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr PO-42.
Nonredundant Roles of Platelet Glycoprotein VI and Integrin αIIbβ3 in Fibrin-Mediated Microthrombus Formation
Authors: Perrella Gina , Huang Jingnan , Provenzale Isabella , Swieringa Frauke , Heubel-Moenen Floor C.J.I. , Farndale Richard W. , Roest Mark , van der Meijden Paola E.J. , Thomas Mark , Ariëns Robert A.S. , Jandrot-Perrus Martine , Watson Steve P. , Heemskerk Johan W.M. 
Published: December 2020

Objective:
Fibrin is considered to strengthen thrombus formation via integrin αIIbβ3, but recent findings indicate that fibrin can also act as ligand for platelet glycoprotein VI.

Approach and Results:

To investigate the thrombus-forming potential of fibrin and the roles of platelet receptors herein, we generated a range of immobilized fibrin surfaces, some of which were cross-linked with factor XIIIa and contained VWF-BP (von Willebrand factor-binding peptide). Multicolor microfluidics assays with whole-blood flowed at high shear rate (1000 s
−1
) indicated that the fibrin surfaces, regardless of the presence of factor XIIIa or VWF-BP, supported platelet adhesion and activation (P-selectin expression), but only microthrombi were formed consisting of bilayers of platelets. Fibrinogen surfaces produced similar microthrombi. Markedly, tiggering of coagulation with tissue factor or blocking of thrombin no more than moderately affected the fibrin-induced microthrombus formation. Absence of αIIbβ3 in Glanzmann thrombasthenia annulled platelet adhesion. Blocking of glycoprotein VI with Fab 9O12 substantially, but incompletely reduced platelet secretion, Ca
2+
signaling and aggregation, while inhibition of Syk further reduced these responses. In platelet suspension, glycoprotein VI blockage or Syk inhibition prevented fibrin-induced platelet aggregation. Microthrombi on fibrin surfaces triggered only minimal thrombin generation, in spite of thrombin binding to the fibrin fibers.

Conclusions:

Together, these results indicate that fibrin fibers, regardless of their way of formation, act as a consolidating surface in microthrombus formation via nonredundant roles of platelet glycoprotein VI and integrin αIIbβ3 through signaling via Syk and low-level Ca
2+
rises.