Impact of comorbidities on the mortality benefits of lung cancer screening: a post-hoc analysis of PLCO and NLST trials.

Hypothesis: To evaluate how comorbidities affect mortality benefits of lung cancer screening (LCS) with low-dose computed-tomography (LDCT).

Methods: We developed a comorbidity index (PLCO-ci) using LCS-eligible participants' data from the Prostate Lung Colorectal and Ovarian (PLCO) trial (training set) and the National Lung Screening Trial (NLST) (validation set). PLCO-ci predicts 5-year non-lung cancer (LC) mortality using a regularized Cox model; with performance evaluated by the area under the ROC curve (ROC).

Lead time trajectory of blood-based protein biomarkers for detection of pancreatic cancer based on repeat testing.

In the current study, we assessed whether repeated measurements of a panel of protein biomarkers with relevance to pancreatic ductal adenocarcinoma (PDAC) improves lead time performance for earlier detection over a single timepoint measurement. Specifically, CA125, CEA, LRG1, REG3A, THBS2, TIMP1, TNRFSF1A as well as CA19-9 were assayed in serially collected pre-diagnostic plasma from 242 PDAC cases and 242 age- and sex-matched non-case control participants in the PLCO cohort. We compared performance estimates of a parametric empirical Bayes (PEB) algorithm, which incorporates participant biomarker history, to that of a single-threshold (ST) method.

The Reverse Backlash: How the Success of Populist Radical Right Parties Relates to More Positive Immigration Attitudes.

What is the relationship between the electoral success of populist radical right parties (PRRPs) and public attitudes toward immigration? Previous research suggests that PRRP success can lead to more negative attitudes due to the breaking down of antiprejudice norms and more prominent anti-immigration party cues. However, we argue that greater PRRP success could have a positive relationship with immigration attitudes, reflecting negative partisanship, polarization, and a desire to reemphasize antiprejudice norms, which we call a "reverse backlash effect." Using the best available electoral and public opinion data across the last thirty years in twenty-four European countries, our TSCS analyses show the predominance of such "reverse backlash effects" across several operationalizations of PRRP success.

Validation of a prognostic blood-based sphingolipid panel for men with localized prostate cancer followed on active surveillance.

Background: We previously reported that increases in circulating sphingolipids are associated with elevated risk of biopsy Gleason grade group (GG) upgrading in men on Active Surveillance (AS) for prostate cancer. Here, we aimed to validate these findings and establish a blood-based sphingolipid biomarker panel for identifying men on AS who are at high-risk of biopsy GG upgrading.

Methods: Men diagnosed with low- or intermediate-risk prostate cancer in one of two AS cohorts (CANARY PASS and MDACC) were followed for GG upgrading after diagnostic and confirmatory biopsy.

Antibiotic-induced loss of gut microbiome metabolic output correlates with clinical responses to CAR T-cell therapy.

Antibiotic-induced microbiome dysbiosis is widespread in oncology, adversely affecting outcomes and side effects of various cancer treatments, including immune checkpoint inhibitors and chimeric antigen receptor T (CAR-T) cell therapies. In this study, we observed that prior exposure to broad-spectrum ABX with extended anaerobic coverage like piperacillin-tazobactam and meropenem was associated with worsened anti-CD19 CAR-T therapy survival outcomes in large B-cell lymphoma patients (n=422), compared to other ABX classes. In a discovery subset of these patients (n=67), we found that the use of these ABX was in turn associated with substantial dysbiosis of gut microbiome function, resulting in significant alterations of the gut and blood metabolome, including microbial effectors such as short-chain fatty acids (SCFAs) and other anionic metabolites, findings that were largely reproduced in an external validation cohort (n=58).