Automated Breast Density Assessment for Full-Field Digital Mammography and Digital Breast Tomosynthesis.

Mammographic density is a strong risk factor for breast cancer and is reported clinically as part of Breast Imaging Reporting and Data System (BI-RADS) results issued by radiologists. Automated assessment of density is needed that can be used for both full-field digital mammography (FFDM) and digital breast tomosynthesis (DBT) as both types of exams are acquired in standard clinical practice. We trained a deep learning model to automate the estimation of BI-RADS density from a prospective Washington University clinic-based cohort of 9,714 women, entering into the cohort in 2013 with follow-up through October 31, 2020.

Multiomic and clinical analysis of multiply recurrent meningiomas reveals risk factors, underlying biology, and insights into evolution.

An important subset of meningiomas behaves aggressively and is characterized by multiple recurrences. We identify clinical, genetic, and epigenetic predictors of multiply recurrent meningiomas (MRMs) and evaluate the evolution of these meningiomas in patient-matched samples. On multivariable binomial logistic regression, MRMs were significantly associated with male sex ( = 0.

Stromal reprogramming overcomes resistance to RAS-MAPK inhibition to improve pancreas cancer responses to cytotoxic and immune therapy.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy that is often resistant to therapy. An immune suppressive tumor microenvironment (TME) and oncogenic mutations in have both been implicated as drivers of resistance to therapy. Mitogen-activated protein kinase (MAPK) inhibition has not yet shown clinical efficacy, likely because of rapid acquisition of tumor-intrinsic resistance.

Evaluation of Ki-67 expression and large cell content as prognostic markers in MZL: a multicenter cohort study.

Marginal zone lymphoma (MZL) can have varied presentations and pathologic features, including high Ki-67 expression ( > 20%) as well as increased numbers of large B cells (LC). However, there are limited data available demonstrating the prognostic significance of these variables in patients with MZL. In this multi-institutional retrospective cohort study of patients with MZL treated at 10 centers, we evaluated the association between the presence of Ki-67 expression and increased LCs on survival and risk of histologic transformation (HT).

N-Linked Fucosylated Glycans Are Biomarkers for Prostate Cancer with a Neuroendocrine and Metastatic Phenotype.

Prostate cancer is a heterogeneous disease with a spectrum of pathology and outcomes ranging from indolent to lethal. Although there have been recent advancements in prognostic tissue biomarkers, limitations still exist. We leveraged matrix-assisted laser desorption/ionization imaging of formalin-fixed, paraffin embedded prostate cancer specimens to determine if N-linked glycans expressed in the extracellular matrix of lethal neuroendocrine prostate cancer were also expressed in conventional prostate adenocarcinomas that were associated with poor outcomes.

Granulocyte colony-stimulating factor protects against arthritogenic alphavirus pathogenesis in a type I IFN-dependent manner.

Arthritogenic alphaviruses cause disease characterized by fever, rash, and incapacitating joint pain. Alphavirus infection stimulates robust inflammatory responses in infected hosts, leading to the upregulation of several cytokines, including granulocyte colony-stimulating factor (G-CSF). G-CSF is secreted by endothelial cells, fibroblasts, macrophages, and monocytes and binds to colony stimulating factor 3 receptor (CSF3R, also known as G-CSFR) on the surface of myeloid cells.

Obesity-Associated Changes in Immune Cell Dynamics During Alphavirus Infection Revealed by Single Cell Transcriptomic Analysis.

Obesity induces diverse changes in host immunity, resulting in worse disease outcomes following infection with various pathogens, including arthritogenic alphaviruses. However, the impact of obesity on the functional landscape of immune cells during arthritogenic alphavirus infection remains unexplored. Here, we used single-cell RNA sequencing (scRNA-seq) to dissect the blood and tissue immune responses to Mayaro virus (MAYV) infection in lean and obese mice.

68 Ga-DOTATATE and 18 F-FDG PET/CT in a Rapidly Progressing Lymphoma.

68 Ga-DOTATATE PET/CT targeting somatostatin receptors is commonly utilized in the imaging of neuroendocrine tumors. However, other malignancies such as lymphomas (both Hodgkin and non-Hodgkin) also have expression of somatostatin receptors, albeit to a lesser degree compared with the neuroendocrine tumors, and thus can be positive on a 68 Ga-DOTATATE PET/CT. We describe an atypical presentation of an aggressive large B-cell lymphoma mimicking a metastatic neuroendocrine tumor at initial presentation with high somatostatin receptor expression demonstrated on the 68 Ga-DOTATATE PET/CT and a rapidly progressing course on the subsequent 18 F-FDG PET/CT.

Impact of site-specific conjugation strategies on the pharmacokinetics of antibody conjugated radiotherapeutics.

Antibody radionuclide conjugates are an emerging modality for targeted imaging and potent therapy of disseminated disease. Coupling of radionuclides to monoclonal antibodies (mAbs) is typically achieved by applying non-site-specific labelling techniques. With the ambition of reducing variability, increasing labelling efficacy and stability, several site-specific conjugation strategies have been developed in recent years for toxin- and fluorophore-mAb conjugates.

Primary Results of NRG-RTOG1106/ECOG-ACRIN 6697: A Randomized Phase II Trial of Individualized Adaptive (chemo)Radiotherapy Using Midtreatment F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Stage III Non-Small Cell Lung Cancer.

Purpose: NRG-RTOG0617 demonstrated a detrimental effect of uniform high-dose radiation in stage III non-small cell lung cancer. NRG-RTOG1106/ECOG-ACRIN6697 (ClinicalTrials.gov identifier: NCT01507428), a randomized phase II trial, studied whether midtreatment F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) can guide individualized/adaptive dose-intensified radiotherapy (RT) to improve and predict outcomes in patients with this disease.

Menopausal Hormone Therapy Use Among Postmenopausal Women.

Importance: Menopausal hormone therapy (MHT) is the treatment of choice for symptoms of menopause. However, its adoption is hindered by the risk-benefit trade-off in relation to acute and chronic diseases.

Objective: To evaluate trends in and correlates of MHT use among postmenopausal women in the US from 1999 to March 2020.

Multidimensional profiling of human T cells reveals high CD38 expression, marking recent thymic emigrants and age-related naive T cell remodeling.

Thymic involution is a key factor in human immune aging, leading to reduced thymic output and a decline in recent thymic emigrant (RTE) naive T cells in circulation. Currently, the precise definition of human RTEs and their corresponding cell surface markers lacks clarity. Analysis of single-cell RNA-seq/ATAC-seq data distinguished RTEs by the expression of SOX4, IKZF2, and TOX and CD38 protein, whereby surface CD38 expression universally identified CD8 and CD4 RTEs.

Usability Testing of a Web Tool for Dissemination and Implementation Science Models.

Unlabelled: Dissemination and Implementation science is dedicated to increasing the speed of evidence-based research translated into practice as guided by one or multiple D&I theories, models, and frameworks. The Dissemination and Implementation Models in Health Research and Practice web tool guides users on how to plan, select, combine, adapt, use, and assess theories, models, and frameworks. This paper describes usability testing to update the web tool.

Plasma Ceramide C24:0/C16:0 Ratio is Associated with Improved Survival in Patients with Pancreatic Ductal Adenocarcinoma.

Background: Pancreatic ductal adenocarcinoma (PDAC) has a high fatality rate, with surgery as the only curative treatment. Identification of new biomarkers related to survival may help guide discovery of new pathophysiologic pathways and potential therapeutic targets. As long-chain ceramides have been linked to tumor proliferation, we sought to determine if ceramide levels were prognostic in PDAC.

Treatment resistance to melanoma therapeutics on a single cell level.

Therapy targeting the BRAF-MEK cascade created a treatment revolution for patients with BRAF mutant advanced melanoma. Unfortunately, 80% patients treated will progress by 5 years follow-up. Thus, it is imperative we study mechanisms of melanoma progression and therapeutic resistance.