Cell-free DNA methylation-based inflammation score as a marker for hepatocellular carcinoma among people living with HIV.

Background: People living with the human immunodeficiency virus (HIV) are at a greater risk of developing hepatocellular carcinoma (HCC), potentially due to the stimulation of inflammation by HIV infection. Inflammation-related DNA methylation signatures obtained in liquid biopsy, such as circulating cell-free DNA (cfDNA), may serve as promising minimally invasive biomarkers that can inform diagnosis of HCC.

Methods: Using data from 249 individuals with HIV (114 individuals with normal liver conditions, 69 with fibrosis, 30 with cirrhosis, and 36 with HCC), we constructed a cfDNA methylation-based inflammation score (inflammation-DNAm score) based on 54 CpGs previously associated with circulating C-reactive protein concentrations.

Integrating machine learning-predicted circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) in metastatic breast cancer: A proof of principle study on endocrine resistance profiling.

The study explored endocrine resistance by leveraging machine learning to establish the prognostic stratification of predicted Circulating tumor cells (CTCs), assessing its integration with circulating tumor DNA (ctDNA) features and contextually evaluate the potential of CTCs-based transcriptomics. 1118 patients with a diagnosis of luminal-like Metastatic Breast Cancer (MBC) were characterized for ctDNA through NGS before treatment start, predicted CTCs were computed through a K nearest neighbor algorithm. Differences across subgroups were analyzed through chi square or Fisher's exact test according to sample size and corrected for False Discovery Rate.

Northwestern University resource and education development initiatives to advance collaborative artificial intelligence across the learning health system.

Introduction: The rapid development of artificial intelligence (AI) in healthcare has exposed the unmet need for growing a multidisciplinary workforce that can collaborate effectively in the learning health systems. Maximizing the synergy among multiple teams is critical for Collaborative AI in Healthcare.

Methods: We have developed a series of data, tools, and educational resources for cultivating the next generation of multidisciplinary workforce for Collaborative AI in Healthcare.

Interplay between ESR1/PIK3CA codon variants, oncogenic pathway alterations and clinical phenotype in patients with metastatic breast cancer (MBC): comprehensive circulating tumor DNA (ctDNA) analysis.

Background: although being central for the biology and druggability of hormone-receptor positive, HER2 negative metastatic breast cancer (MBC), ESR1 and PIK3CA mutations are simplistically dichotomized as mutated or wild type in current clinical practice.

Methods: The study analyzed a multi-institutional cohort comprising 703 patients with luminal-like MBC characterized for circulating tumor DNA through next generation sequencing (NGS). Pathway classification was defined based on previous work (i.

Cyclin-Dependent Kinase 4/6 Inhibitors Beyond Progression in Metastatic Breast Cancer: A Retrospective Real-World Biomarker Analysis.

Purpose: As the continuation beyond progression (BP) of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) is becoming increasingly attractive for the treatment of patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC), the definition of resistance factors is crucial. The aim of the study was to investigate the impact of CDK 4/6i BP and to explore potential genomic stratification factors.

Materials And Methods: We retrospectively analyzed a multi-institutional cohort of patients with HR-positive HER2-negative MBC characterized for circulating tumor DNA through next-generation sequencing before treatment start.

Accelerating Food Allergy Research: Need for a Data Commons.

Food allergy is a significant health problem affecting approximately 8% of children and 11% of adults in the United States. It exhibits all the characteristics of a "complex" genetic trait; therefore, it is necessary to look at very large numbers of patients, far more than exist at any single organization, to eliminate gaps in the current understanding of this complex chronic disorder. Advances may be achieved by bringing together food allergy data from large numbers of patients into a Data Commons, a secure and efficient platform for researchers, comprising standardized data, available in a common interface for download and/or analysis, in accordance with the FAIR (Findable, Accessible, Interoperable, and Reusable) principles.

Augmented Intelligence to Identify Patients With Advanced Heart Failure in an Integrated Health System.

Background: Timely referral for specialist evaluation in patients with advanced heart failure (HF) is a Class 1 recommendation. However, the transition from stage C HF to advanced or stage D HF often goes undetected in routine care, resulting in delayed referral and higher mortality rates.

Objectives: The authors sought to develop an augmented intelligence-enabled workflow using machine learning to identify patients with stage D HF and streamline referral.

Telepathology in Nigeria for Global Health Collaboration.

Inadequate pathology personnel and high cost of running a Pathology facility are factors affecting access to timely and quality pathology services in resource-constrained settings. Telepathology is a novel technology that allows Pathologists to remotely assess collected samples. Though the initial cost of setting up a telepathology facility is high, its overall benefits far outweigh the cost.

Genomic Landscape of Advanced Solid Tumors in Circulating Tumor DNA and Correlation With Tissue Sequencing: A Single Institution's Experience.

Purpose: Circulating tumor DNA (ctDNA) has emerged as a promising noninvasive biomarker for baseline characterization and longitudinal monitoring of a tumor throughout disease management. The aim of this study was to evaluate the utility of ctDNA across a wide spectrum of tumor types.

Methods: We retrospectively identified 1,763 patients with advanced cancers who had next-generation sequencing of ctDNA or tumor tissue completed by a designated commercial assay at Northwestern University.

Accelerated Epigenetic Age Among Women with Invasive Cervical Cancer and HIV-Infection in Nigeria.

Background: Invasive cervical cancer (ICC) is a serious public health burden in Nigeria, where human immunodeficiency virus (HIV) remains highly prevalent. Previous research suggested that epigenetic age acceleration (EAA) could play a role in detection of HIV-associated ICC. However, little research has been conducted on this topic in Africa where the population is most severely affected by HIV-associated ICC.

Outcomes of Cancer Patients with COVID-19 in a Hospital System in the Chicago Metropolitan Area.

Patients with a history of malignancy have been shown to be at an increased risk of COVID-19-related morbidity and mortality. Poorer clinical outcomes in that patient population are likely due to the underlying systemic illness, comorbidities, and the cytotoxic and immunosuppressive anti-tumor treatments they are subjected to. We identified 416 cancer patients with SARS-CoV-2 infection being managed for their malignancy at Northwestern Medicine in Chicago, Illinois, between March and July of 2020.

Modeling the Prognostic Impact of Circulating Tumor Cells Enumeration in Metastatic Breast Cancer for Clinical Trial Design Simulation.

Despite the strong prognostic stratification of circulating tumor cells (CTCs) enumeration in metastatic breast cancer (MBC), current clinical trials usually do not include a baseline CTCs in their design. This study aimed to generate a classifier for CTCs prognostic simulation in existing datasets for hypothesis generation in patients with MBC. A K-nearest neighbor machine learning algorithm was trained on a pooled dataset comprising 2436 individual MBC patients from the European Pooled Analysis Consortium and the MD Anderson Cancer Center to identify patients likely to have CTCs ≥ 5/7 mL blood (StageIVaggressive vs StageIVindolent).

Development of Food Allergy Data Dictionary: Toward a Food Allergy Data Commons.

Background: Food allergy (FA) data lacks a common base of terminology and hinders data exchange among institutions.

Objective: To examine the current FA concept coverage by clinical terminologies and to develop and evaluate a Food Allergy Data Dictionary (FADD).

Methods: Allergy/immunology templates and patient intake forms from 4 academic medical centers with expertise in FA were systematically reviewed, and in-depth discussions with a panel of FA experts were conducted to identify important FA clinical concepts and data elements.

Positive predictive value of ERBB2 copy number gain by tissue or circulating tumor DNA next-generation sequencing across advanced cancers.

Background: The correlation of ERBB2 copy number gain (CNG) from tissue or circulating tumor DNA (ctDNA) by next-generation sequencing (NGS) with standard HER2 tissue evaluation is not well understood.

Materials And Methods: We retrospectively identified patients with ERBB2 CNG on commercial NGS. We described their clinical-pathologic features and calculated the positive predictive value (PPV) of ERBB2 CNG by NGS for HER2-positivity by IHC and FISH testing.

Comparison of myeloid neoplasms with nonclassic 3q26.2/MECOM versus classic inv(3)/t(3;3) rearrangements reveals diverse clinicopathologic features, genetic profiles, and molecular mechanisms of MECOM activation.

MECOM rearrangements are recurrent in myeloid neoplasms and associated with poor prognosis. However, only inv(3)(q21q26.2) and t(3;3)(q21;q26.

Cell-free DNA comparative analysis of the genomic landscape of first-line hormone receptor-positive metastatic breast cancer from the US and China.

Purpose: Meaningful comparison of mutational landscapes across ethnic groups requires the use of standardized platform technology. We have used a harmonized NGS-based liquid biopsy assay to explore the differential genomic landscape of patients with initially hormone receptor-positive (HR+), HER2-negative MBC of first line metastasis or primary Stage IV at diagnosis from the United States (US) and China (CN).

Methods: Plasma circulating tumor DNA (ctDNA) from 27 US patients and 65 CN patients was sequenced using the harmonized CLIA-certified, 152-gene PredicineCare™ liquid biopsy assay.

The Use of Serial Circulating Tumor DNA to Detect Resistance Alterations in Progressive Metastatic Breast Cancer.

Purpose: Circulating tumor DNA (ctDNA) is a promising tool for noninvasive longitudinal monitoring of genomic alterations. We analyzed serial ctDNA to characterize genomic evolution in progressive metastatic breast cancer.

Experimental Design: This was a retrospective cohort between 2015 and 2019 obtained under an Institutional Review Board-approved protocol at Northwestern University (Chicago, IL).

Understanding the organ tropism of metastatic breast cancer through the combination of liquid biopsy tools.

Background: Liquid biopsy provides real-time data about prognosis and actionable mutations in metastatic breast cancer (MBC). The aim of this study was to explore the combination of circulating tumour DNA (ctDNA) analysis and circulating tumour cells (CTCs) enumeration in estimating target organs more susceptible to MBC involvement.

Methods: This retrospective study analysed 88 MBC patients characterised for both CTCs and ctDNA at baseline.

Landscape of circulating tumour DNA in metastatic breast cancer.

Background: We describe the genomic landscape of circulating tumour DNA (ctDNA) across pathological subtypes of metastatic breast cancer.

Methods: 255 clinically annotated patients with ctDNA testing by Guardant360 were stratified into HR+, HER2+, and TNBC cohorts. Frequency and heterogeneity of alterations were reported.

Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study.

Background: Data on patients with COVID-19 who have cancer are lacking. Here we characterise the outcomes of a cohort of patients with cancer and COVID-19 and identify potential prognostic factors for mortality and severe illness.

Methods: In this cohort study, we collected de-identified data on patients with active or previous malignancy, aged 18 years and older, with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from the USA, Canada, and Spain from the COVID-19 and Cancer Consortium (CCC19) database for whom baseline data were added between March 17 and April 16, 2020.

Performance of a novel Next Generation Sequencing circulating tumor DNA (ctDNA) platform for the evaluation of samples from patients with metastatic breast cancer (MBC).

Circulating tumor DNA (ctDNA) is gaining momentum as sensitive diagnostic tool for advanced disease characterization because of its ability both to capture the tumor's heterogeneity and its dynamic adaptations. However, the consistency between all the available platforms is still debated. The aim of the study was to explore the performance of the novel diagnostic NGS platform PredicinePLUS™ and to compare its results with the clinically available Guardant360™ platform for possible analytical inconsistencies.

HIV status, age at cervical Cancer screening and cervical cytology outcomes in an opportunistic screening setting in Nigeria: a 10-year Cross sectional data analysis.

Background: Invasive cervical cancer (ICC) is more prevalent in HIV infected women and occurs at younger median age than in HIV negative women. Organized cervical cancer screening (CCS) is presently lacking in Nigeria, and the age at CCS is not known in this population. We sought to examine the age at CCS, the cytology outcomes and whether outcomes differ by HIV infection status in an opportunistic screening setting.

Sustainability considerations for clinical and translational research informatics infrastructure.

A robust biomedical informatics infrastructure is essential for academic health centers engaged in translational research. There are no templates for what such an infrastructure encompasses or how it is funded. An informatics workgroup within the Clinical and Translational Science Awards network conducted an analysis to identify the scope, governance, and funding of this infrastructure.