tbuckley/cabot-search huggingface dataset:
Association of <i>Fusobacterium nucleatum</i> with Specific T-cell Subsets in the Colorectal Carcinoma Microenvironment
Authors: Jennifer Borowsky, Koichiro Haruki, Mai Chan Lau, Andressa Dias Costa, Juha P. Väyrynen, Tomotaka Ugai, Kota Arima, Annacarolina da Silva, Kristen D. Felt, Melissa Zhao, Carino Gurjao, Tyler S. Twombly, Kenji Fujiyoshi, Sara A. Väyrynen, Tsuyoshi Hamada, Kosuke Mima, Susan Bullman, Tabitha A. Harrison, Amanda I. Phipps, Ulrike Peters, Kimmie Ng, Jeffrey A. Meyerhardt, Mingyang Song, Edward L. Giovannucci, Kana Wu, Xuehong Zhang, Gordon J. Freeman, Curtis Huttenhower, Wendy S. Garrett, Andrew T. Chan, Barbara A. Leggett, Vicki L.J. Whitehall, Neal Walker, Ian Brown, Mark Bettington, Reiko Nishihara, Charles S. Fuchs, Jochen K. Lennerz, Marios Giannakis, Jonathan A. Nowak, Shuji Ogino
Journal: Clinical Cancer Research (2021)

Abstract Purpose: While evidence indicates that Fusobacterium nucleatum (F. nucleatum) may promote colorectal carcinogenesis through its suppressive effect on T-cell–mediated antitumor immunity, the specific T-cell subsets involved remain uncertain. Experimental Design: We measured F. nucleatum DNA within tumor tissue by quantitative PCR on 933 cases (including 128 F. nucleatum–positive cases) among 4,465 incident colorectal carcinoma cases in two prospective cohorts. Multiplex immunofluorescence combined with digital image analysis and machine learning algorithms for CD3, CD4, CD8, CD45RO (PTPRC isoform), and FOXP3 measured various T-cell subsets. We leveraged data on Bifidobacterium, microsatellite instability (MSI), tumor whole-exome sequencing, and M1/M2-type tumor-associated macrophages [TAM; by CD68, CD86, IRF5, MAF, and MRC1 (CD206) multimarker assay]. Using the 4,465 cancer cases and inverse probability weighting method to control for selection bias due to tissue availability, multivariable-adjusted logistic regression analysis assessed the association between F. nucleatum and T-cell subsets. Results: The amount of F. nucleatum was inversely associated with tumor stromal CD3+ lymphocytes [multivariable OR, 0.47; 95% confidence interval (CI), 0.28–0.79, for F. nucleatum–high vs. -negative category; Ptrend = 0.0004] and specifically stromal CD3+CD4+CD45RO+ cells (corresponding multivariable OR, 0.52; 95% CI, 0.32–0.85; Ptrend = 0.003). These relationships did not substantially differ by MSI status, neoantigen load, or exome-wide tumor mutational burden. F. nucleatum was not significantly associated with tumor intraepithelial T cells or with M1 or M2 TAMs. Conclusions: The amount of tissue F. nucleatum is associated with lower density of stromal memory helper T cells. Our findings provide evidence for the interactive pathogenic roles of microbiota and specific immune cells.
Abstract PS14-26: Comparison of clinicopathological features in BRCA-wild type and -mutated male breast cancer patients
Authors: Izzet Dogan, Esra Aydın, Hülya Yazıcı, Pınar Saip
Journal: Cancer Research (2021)

Abstract Background: BRCA mutations result in a variety of cancer types such as breast, ovarian, and prostate. 4-40% of the patients with male breast cancer have BRCA mutations, and BRCA 2 mutation is more commonly detected. In this study, we compared the clinicopathological characteristics of BRCA- wild type and -mutated male breast cancer (MBC). Methods: The data of 43 patients were retrospectively reviewed. Clinical and histopathological data of the patients were recorded. The characteristics of the patients were compared by the chi-square test and Fisher exact test. Survival analysis evaluated with Kaplan-Meier analysis. Results: The median follow-up period was 35.8 months (range, 2.2-225.8). The median age at diagnosis was 58 years (range, 25-81) and not statistically different between groups (p=0.753). 11 (25.6%) of the patients had BRCA mutations. Four (9.3%) patients had BRCA1 mutations, six (14%) patients BRCA2 mutations, and one (2.3%) patients had both BRCA 1 and 2 mutations. Among BRCA- wild type and - mutated patients: estrogen receptor positivity (p=0.055), progesterone receptor positivity (p=0.698), HER2 overexpression (p=0.542), tumor localization (p=0.305), tumor histology (p=0.069), lymph node involvement (p=0.589), tumor stage (p=0.892), and recurrence status (p=0.698) were comparable. The median overall survival was 115.6 months (range, 76.0-155.3), and similar between groups (p=0.647). Conclusions: MBC is rare. In literature, the data of MBC and BRCA mutation is limited, and studies included a low number of patients. In a result, we found that clinicopathological characteristic and prognosis of BRCA-mutated and-wild type MBC was similar. Citation Format: Izzet Dogan, Esra Aydın, Hülya Yazıcı, Pınar Saip. Comparison of clinicopathological features in BRCA-wild type and -mutated male breast cancer patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-26.
Abstract 12821: Genomic Factors Associated With Anthracycline Cardiotoxicity in Pediatric Cancer Survivors
Authors: Marie Chaix, Myriam Lafreniere-Roula, Oyediran Akinrinade, Roderick Yao, Anastasia Miron, Emily Lam, Anne Christie, Ashok Kumar Manickaraj, Stacey Marjerrison, Rejane Dillenburg, Mylène Bassal, Jane Lougheed, Shayna Zelcer, Herschel Rosenberg, David Hodgson, Leonard Sender, Mark Greenberg, Peter Liu, Paul Kantor, Cedric Manlhiot, Luc Mertens, Paul Nathan, Seema Mital
Journal: Circulation (2018)

Introduction: Anthracycline cardiotoxicity is a major cause of morbidity in cancer survivors. Clinical predictors of anthracycline cardiotoxicity are imprecise. Hypothesis: Rare genetic variation m...
Perspectives on expertise in teaching about transgender healthcare: A focus group study with health professional programme teaching staff and transgender community members
Authors: Gareth J. Treharne, Althea Gamble Blakey, Katie Graham, Samuel D. Carrington, Laurel A. McLachlan, Cassie Withey-Rila, Louise Pearman-Beres, Lynley Anderson
Journal: International Journal of Transgender Health (2021)

It is well established that transgender people experience considerable health inequities, which are sustained in part by limited teaching about transgender healthcare for trainee health professionals.The aim of this study was to explore the perspectives of both teaching staff from health professional education programmes and transgender community members on the best ways to teach about transgender healthcare, with a focus on ways of: 1) overcoming barriers to this teaching; and 2) involving community members in this teaching.A research advisory committee was convened to guide the project and included transgender community members, teaching staff from health professional programmes, and trainee health professionals in Aotearoa/New Zealand. Three preliminary focus groups were held with 10 transgender community members. These community members were then invited to act as transgender community 'ambassadors' in focus groups with teaching staff based on suggestions from the advisory committee. Six focus groups were conducted with 22 teaching staff from a range of health professional education programmes along with at least two transgender community ambassadors.Teaching staff positioned themselves as lacking the expertise to teach about transgender healthcare but also as expert teachers when applying methods such as small group teaching. Transgender participants also positioned themselves as having expertise arising primarily from their own experiences and acknowledged that effective teaching about transgender healthcare would need to cover a diversity of transgender identities and healthcare outside their own experiences. Teaching staff and transgender community members were keen to pool expertise and thus overcome the shared sense of lacking the expertise to teach about transgender healthcare.These findings provide insights into the current barriers to teaching about transgender healthcare and provide future directions for staff development on teaching about transgender healthcare and ways of safely involving transgender community members in teaching.
Clinical-grade whole-genome sequencing and 3′ transcriptome analysis of colorectal cancer patients
Authors: Agata Stodolna, Miao He, Mahesh Vasipalli, Zoya Kingsbury, Jennifer Becq, Joanne D. Stockton, Mark P. Dilworth, Jonathan James, Toju Sillo, Daniel Blakeway, Stephen T. Ward, Tariq Ismail, Mark T. Ross, Andrew D. Beggs
Journal: Genome Medicine (2021)

Abstract Background Clinical-grade whole-genome sequencing (cWGS) has the potential to become the standard of care within the clinic because of its breadth of coverage and lack of bias towards certain regions of the genome. Colorectal cancer presents a difficult treatment paradigm, with over 40% of patients presenting at diagnosis with metastatic disease. We hypothesised that cWGS coupled with 3′ transcriptome analysis would give new insights into colorectal cancer. Methods Patients underwent PCR-free whole-genome sequencing and alignment and variant calling using a standardised pipeline to output SNVs, indels, SVs and CNAs. Additional insights into the mutational signatures and tumour biology were gained by the use of 3′ RNA-seq. Results Fifty-four patients were studied in total. Driver analysis identified the Wnt pathway gene APC as the only consistently mutated driver in colorectal cancer. Alterations in the PI3K/mTOR pathways were seen as previously observed in CRC. Multiple private CNAs, SVs and gene fusions were unique to individual tumours. Approximately 30% of patients had a tumour mutational burden of &gt; 10 mutations/Mb of DNA, suggesting suitability for immunotherapy. Conclusions Clinical whole-genome sequencing offers a potential avenue for the identification of private genomic variation that may confer sensitivity to targeted agents and offer patients new options for targeted therapies.
Equitable Access to Research Benefits: Considerations for COVID-19 Vaccine Development and Clinical Trial Crossover
Authors: Danish Zaidi, Jennifer Miller, Tanvee Varma, Dowin Boatright, Phoebe Friesen
Journal: The American Journal of Bioethics (2021)

Click to increase image sizeClick to decrease image sizeThis article refers to:Structural Racism in the COVID-19 Pandemic: Moving ForwardThis article is referred to by:An Open Dialogue on Health Disparities and Structural Racism: Response to Open Peer Commentaries
Molecular Imaging of Infarcted Heart by Biofunctionalized Gold Nanoshells
Authors: Tamara Muñoz‐Ortiz, Jie Hu, Dirk H. Ortgies, Shreya Shrikhande, Paula Zamora‐Perez, Miriam Granado, Daniel González‐Hedström, María de la Fuente‐Fernández, Ángel Luis García‐Villalón, Laura Andrés‐Delgado, Emma Martín Rodríguez, Río Aguilar, Fernando Alfonso, José García Solé, Pilar Rivera Gil, Daniel Jaque, Fernando Rivero
Journal: Advanced Healthcare Materials (2021)

Abstract The unique combination of physical and optical properties of silica (core)/gold (shell) nanoparticles (gold nanoshells) makes them especially suitable for biomedicine. Gold nanoshells are used from high‐resolution in vivo imaging to in vivo photothermal tumor treatment. Furthermore, their large scattering cross‐section in the second biological window (1000–1700 nm) makes them also especially adequate for molecular optical coherence tomography (OCT). In this work, it is demonstrated that, after suitable functionalization, gold nanoshells in combination with clinical OCT systems are capable of imaging damage in the myocardium following an infarct. Since both inflammation and apoptosis are two of the main mechanisms underlying myocardial damage after ischemia, such damage imaging is achieved by endowing gold nanoshells with selective affinity for the inflammatory marker intercellular adhesion molecule 1 (ICAM‐1), and the apoptotic marker phosphatidylserine. The results here presented constitute a first step toward a fast, safe, and accurate diagnosis of damaged tissue within infarcted hearts at the molecular level by means of the highly sensitive OCT interferometric technique.
Association of Convalescent Plasma Treatment With Clinical Outcomes in Patients With COVID-19
Authors: Perrine Janiaud, Cathrine Axfors, Andreas M. Schmitt, Viktoria Gloy, Fahim Ebrahimi, Matthias Hepprich, Emily R. Smith, Noah A. Haber, Nina Khanna, David Moher, Steven N. Goodman, John P. A. Ioannidis, Lars G. Hemkens
Journal: JAMA (2021)

Convalescent plasma is a proposed treatment for COVID-19.
Abstract PS6-48: Clinicopathologic features and follow-up outcomes of breast cancers with HER2 FISH group 3 Results: A single institution experience
Authors: Huina Zhang, Rana Ajabnoor, David Hicks, Bradley Turner
Journal: Cancer Research (2021)

Abstract INTRODUCTION: There is dearth information on the long-term outcome and role of HER2 targeted therapy in breast cancer patients in the HER2 FISH group 3 category, which is defined as breast cancer with a HER2/CEP17 ratio &amp;lt; 2 and HER2 copy number ≥ 6 signals/cell. In this study, we report the clinicopathologic features and outcomes of breast cancer patients in the HER2 FISH group 3 category at our institution. METHODS: We identified 52/2,874 (1.8%) breast cancer patients with HER2 FISH group 3 results between 1/2007 and 3/2020. 28 of these 52 patients had available detailed clinicopathologic and follow-up data, with an average follow-up of 38.5 months. RESULTS: Most of the cases with group 3 FISH results were high grade ductal carcinomas with positive hormonal receptor expressions and equivocal HER2 expression by immunohistochemistry. Among all the clinicopathologic variables, only tumor size (p=0.048) significantly contributed to the poor clinical outcomes. HER2 copy number failed to show any significant association with histologic grade, tumor size, clinical stage, hormonal receptor status or disease outcomes. There was no statistically significant difference in disease outcome between patients who were treated with HER2 targeted therapy and patients who did not receive HER2 targeted therapy, regardless of the HER2 copy number or clinical stage (Table 1). CONCLUSION: Our preliminary findings suggest that certain patients with HER2 FISH group 3 category breast cancer may not need HER-2 targeted therapy. Larger-scale studies are needed to further evaluate which HER2 FISH group 3 results are more likely to benefit from the HER-2 targeted therapy. Table 1. Response to HER2 targeted therapy in HER2 FISH group 3 breast cancer patients based on HER2 copy numbers and clinical stageHER 2 targeted therapyp-valueGivenNot givenTotal populationGood outcome (n=21)1380.371Bad outcome (n=7)61HER2 copy number &amp;lt; 10Good outcome (n=16)1060.366Bad outcome (n=7)61HER2 copy number ≥ 10Good outcome (n=5)321.000Bad outcome (n=0)00Stage I-IIGood outcome (n=16)970.737Bad outcome (n=3)21Stage III-IVGood outcome (n=5)410.343Bad outcome (n=4)40*Good outcome = No evidence of disease**Bad outcome = Local recurrence, distant metastasis, and/or died of disease Citation Format: Huina Zhang, Rana Ajabnoor, David Hicks, Bradley Turner. Clinicopathologic features and follow-up outcomes of breast cancers with HER2 FISH group 3 Results: A single institution experience [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-48.
Abstract PD15-10: Identification of BBOX1 as a therapeutic target in triple-negative breast cancer
Authors: Chengheng Liao, Yang Zhang, Cheng Fan, Laura E. Herring, Juan Liu, Jason W. Locasale, Mamoru Takada, Jin Zhou, Giada Zurlo, Lianxin Hu, Jeremy M. Simon, Travis S. Ptacek, Victor G. Andrianov, Einars Loza, Yan Peng, Huanghe Yang, Charles M. Perou, Qing Zhang
Journal: Cancer Research (2021)

Abstract Triple-negative breast cancer (TNBC), which accounts for 15-20% of breast cancers, causes the highest mortality rate among all breast cancer subtypes. Due to its heterogeneity and lack of estrogen and progesterone receptor or human epidermal growth factor receptor 2 expression, valuable targeted therapy is limited. Therefore, it is critical to identify novel therapeutic targets in TNBC. 2-oxoglutarate (2-OG)-dependent enzymes, including prolyl hydroxylases (EglN1-3), histone demethylases (for example, KDM5A) and DNA hydroxylases (such as TET1-3), are associated with cancer progression. However, the role of these enzymes in TNBC has never been systematically studied. Here, by performing a functional siRNA screening for 2-OG-dependent enzymes, we identified gamma-butyrobetaine hydroxylase 1 (BBOX1) as an essential gene for TNBC tumorigenesis. BBOX1 depletion inhibits TNBC cell growth, while not affecting normal breast cells. Mechanistically, BBOX1 binds with the calcium channel inositol-1,4,5-trisphosphate receptor type 3 (IP3R3) in an enzymatic-dependent manner and prevents its ubiquitination and proteasomal degradation. BBOX1 depletion suppresses IP3R3 mediated endoplasmic reticulum calcium release, therefore impairing calcium-dependent energy-generating processes including mitochondrial respiration and mTORC1 mediated glycolysis, which leads to apoptosis and impaired cell cycle progression in TNBC cells. Therapeutically, genetic depletion or pharmacological inhibition of BBOX1 inhibits TNBC tumor growth in vitro and in vivo. Our study highlights the importance of targeting previously uncharacterized BBOX1-IP3R3-calcium oncogenic signaling axis in TNBC. Citation Format: Chengheng Liao, Yang Zhang, Cheng Fan, Laura E. Herring, Juan Liu, Jason W. Locasale, Mamoru Takada, Jin Zhou, Giada Zurlo, Lianxin Hu, Jeremy M. Simon, Travis S. Ptacek, Victor G. Andrianov, Einars Loza, Yan Peng, Huanghe Yang, Charles M. Perou, Qing Zhang. Identification of BBOX1 as a therapeutic target in triple-negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD15-10.
Clip-line closure with the reopenable clip over line method for a large mucosal defect after gastric endoscopic submucosal dissection
Authors: Tatsuma Nomura, Shinya Sugimoto, Taishi Temma, Jun Oyamada, Akira Kamei
Journal: Endoscopy (2021)

Mucosal defects that occur following large gastric endoscopic submucosal dissection (ESD) are a cause of postoperative bleeding [1] [2] [3]. A standard method for large mucosal defect closure without dead space between the normal mucosa and mucosal defect has not yet been established. We invented clip-line closure with the reopenable clip over line method (ROLM) for complete closure of the mucosal defect left after gastric ESD.
Recommendations on Eliminating Racial Disparities in Multiple Myeloma Therapies: A Step toward Achieving Equity in Healthcare
Authors: Nicole Gormley, Lola Fashoyin-Aje, Trevan Locke, Joseph M. Unger, Richard F. Little, Ajay Nooka, Khalid Mezzi, Mihaela Popa-McKiver, Rachel Kobos, Yelak Biru, Tiffany H. Williams, Kenneth C. Anderson
Journal: Blood Cancer Discovery (2021)

Abstract African Americans are at higher risk of multiple myeloma (MM) yet are underrepresented in clinical trials and reap fewer benefits from novel therapies of the disease. To improve representation of African Americans in MM clinical trials, researchers, healthcare providers, patients, industry partners, and regulators at an FDA–AACR workshop developed recommendations to all stakeholders. The outlined principles offer a road map to addressing disparities broadly in clinical trials.
Required and Voluntary Occupational Use of Hazard Controls for COVID-19 Prevention in Non–Health Care Workplaces — United States, June 2020
Authors: Rachael M. Billock, Matthew R. Groenewold, Hannah Free, Marie Haring Sweeney, Sara E. Luckhaupt
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Certain hazard controls, including physical barriers, cloth face masks, and other personal protective equipment (PPE), are recommended to reduce coronavirus 2019 (COVID-19) transmission in the workplace (1).Evaluation of occupational hazard control use for COVID-19 prevention can identify inadequately protected workers and opportunities to improve use.CDC's National Institute for Occupational Safety and Health used data from the June 2020 SummerStyles survey to characterize required and voluntary use of COVID-19-related occupational hazard controls among U.S. non-health care workers.A survey-weighted regression model was used to estimate the association between employer provision of hazard controls and voluntary use, and stratum-specific adjusted risk differences (aRDs) among workers reporting household incomes <250% and ≥250% of national poverty thresholds were estimated to assess effect modification by income.Approximately one half (45.6%; 95% confidence interval [CI] = 41.0%-50.3%) of non-health care workers reported use of hazard controls in the workplace, 55.5% (95% CI = 48.8%-62.2%) of whom reported employer requirements to use them.After adjustment for occupational group and proximity to others at work, voluntary use was approximately double, or 22.3 absolute percentage points higher, among workers who were provided hazard controls than among those who were not.This effect was more apparent among lower-income (aRD = 31.0%)than among higher-income workers (aRD = 16.3%).Employers can help protect workers from COVID-19 by requiring and encouraging use of occupational hazard controls and providing hazard controls to employees (1).
Abstract SP069: Strategies to reduce cardiac toxicity
Authors: R Jimenez
Journal: Cancer Research (2021)

Abstract Approximately 60-70% of breast cancer (BC) patients receive radiation therapy (RT) as part of their care. Breast or chest wall RT improves locoregional control for BC and also improves BC survival in select populations. However, RT to the cardiac silhouette can be cardiotoxic and radiation induced cardiac toxicity (RIC) affects many breast cancer survivors. The likelihood of RIC is radiation dose dependent and can manifest in multiple forms including cardiovascular disease, heart failure, and/or pericarditis. The risk of cardiovascular disease among patients receiving RT for breast cancer increases linearly with mean heart dose exposure, with no minimum safe threshold. Prior studies have shown an increased risk of both major coronary events and heart failure within 5 years of RT among women with breast cancer, though the latency can be pronounced (10-20 years from exposure) and is further influenced by patient age at treatment as well as pre-existing cardiac risk factors. Therefore, the purpose of this talk is to: 1) discuss the nature and timing of RIC, including those patients most at risk of developing RIC, 2) review national and international cardiology-based guidelines for patient management after chest radiotherapy and 3) detail advances in cardiac sparing radiation techniques intended to reduce the risk of RIC. Ongoing research regarding novel detection and prevention strategies will be highlighted. Citation Format: R Jimenez. Strategies to reduce cardiac toxicity [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SP069.
Clinical activity of BIBW 2992, an irreversible inhibitor of EGFR and HER2 in adenocarcinoma of the lung with mutations in the kinase domain of HER2neu
Authors: J De Greve, L. Decoster, J. De Mey, Pieter In 'T Veld, Caroline Geers, Martine Taton, Mehdi Shahidi, D. Galdermans, E. Teugels, D Schallier
Journal: Journal of Thoracic Oncology (2009)
Upregulation of Alternatively Glycosylated Smoothened (SMO) Is Involved in Doxorubicin (DXR) Resistance in Diffuse Large B-Cell Lymphoma
Authors: Nitin Agarwal, Kranthi Kunkalla, Sandra Sanchez, Amineh Vaghefi, Darius Juskevicius, Alexandar Tzankov, Ramiro E Verdun, Ralf Landgraf, Francisco Vega
Journal: Blood (2017)