A CAR enhancer increases the activity and persistence of CAR T cells.

Although chimeric antigen receptor (CAR) T cell therapies have demonstrated promising clinical outcomes, durable remissions remain limited. To extend the efficacy of CAR T cells, we develop a CAR enhancer (CAR-E), comprising a CAR T cell antigen fused to an immunomodulatory molecule. Here we demonstrate this strategy using B cell maturation antigen (BCMA) CAR T cells for the treatment of multiple myeloma, with a CAR-E consisting of the BCMA fused to a low-affinity interleukin 2 (IL-2).

Interplay between oncolytic measles virus, macrophages and cancer cells induces a proinflammatory tumor microenvironment.

Attenuated measles virus (MV) exerts its oncolytic activity in malignant pleural mesothelioma (MPM) cells that lack type-I interferon (IFN-I) production or responsiveness. However, other cells in the tumor microenvironment (TME), such as myeloid cells, possess functional antiviral pathways. In this study, we aimed to characterize the interplay between MV and the myeloid cells in human MPM.

Further knowledge and developments in resistance mechanisms to immune checkpoint inhibitors.

The past decade has witnessed a revolution in cancer treatment, shifting from conventional drugs (chemotherapies) towards targeted molecular therapies and immune-based therapies, in particular immune-checkpoint inhibitors (ICIs). These immunotherapies release the host's immune system against the tumor and have shown unprecedented durable remission for patients with cancers that were thought incurable, such as metastatic melanoma, metastatic renal cell carcinoma (RCC), microsatellite instability (MSI) high colorectal cancer and late stages of non-small cell lung cancer (NSCLC). However, about 80% of the patients fail to respond to these immunotherapies and are therefore left with other less effective and potentially toxic treatments.

Oncolytic attenuated measles virus encoding NY-ESO-1 induces HLA I and II presentation of this tumor antigen by melanoma and dendritic cells.

Antitumor virotherapy stimulates the antitumor immune response during tumor cell lysis induced by oncolytic viruses (OVs). OV can be modified to express additional transgenes that enhance their therapeutic potential. In this study, we armed the spontaneously oncolytic Schwarz strain of measles viruses (MVs) with the gene encoding the cancer/testis antigen NY-ESO-1 to obtain MVny.

17β-estradiol promotes extracellular vesicle release and selective miRNA loading in ERα-positive breast cancer.

The causes and consequences of abnormal biogenesis of extracellular vesicles (EVs) are not yet well understood in malignancies, including in breast cancers (BCs). Given the hormonal signaling dependence of estrogen receptor-positive (ER+) BC, we hypothesized that 17β-estradiol (estrogen) might influence EV production and microRNA (miRNA) loading. We report that physiological doses of 17β-estradiol promote EV secretion specifically from ER+ BC cells via inhibition of miR-149-5p, hindering its regulatory activity on SP1, a transcription factor that regulates the EV biogenesis factor nSMase2.

Maintenance of Certification in Radiology: Eliciting Radiologist Preferences Using a Discrete Choice Experiment.

Objective: To quantitatively assess radiologists' preferences for Maintenance of Certification (MOC) and Continuing Certification (CC) using a survey of attitudes and perceptions.

Methods: A questionnaire that assessed attitudes and perceptions and included a discrete choice or trade-off task was developed by ACR staff in conjunction with an independent market research agency and the Survey Subcommittee of the ACR Task Force on Certification in Radiology. The trade-off exercise was integrated into this methodology to better understand the underlying utilities or preferences of the components of MOC-CC among respondents and to better enable specific recommendations on how to optimize the current program.

Integration of Art Into Radiological Societies & Educational Conferences: Early Experiences of the 2021 ACR Art Task Force.

Interest in incorporating art into radiology has been growing in recent years. Radiological societies have begun to acknowledge the benefits art can bring to our field. Given this growing interest, a task force was created in 2021 to carry out integration of the arts into the annual American College of Radiology (ACR) meeting.

Direct N- or C-Terminal Protein Labeling Via a Sortase-Mediated Swapping Approach.

Site-specific protein labeling is important in biomedical research and biotechnology. While many methods allow site-specific protein modification, a straightforward approach for efficient N-terminal protein labeling is not available. We introduce a novel sortase-mediated swapping approach for a one-step site-specific N-terminal labeling with a near-quantitative yield.

Compassionate Leadership: Essential for the Future of Tropical Medicine and Global Health.

Compassion-the awareness of suffering coupled with the desire to relieve that suffering-is an evolved human capacity that offers significant benefits for individuals and organizations. While the relief of suffering is central to tropical medicine and global health, compassion is more often assumed than explicit. Global health leaders participating in a compassionate leadership program recently reported that the most common personal barriers to compassionate leadership include inability to regulate workload, perfectionism, and lack of self-compassion; while the most common external challenges include excessive work-related demands, the legacy of colonialism, and the lack of knowledge on how to lead with compassion.

Managing Incidental Findings on Thoracic CT: Lung Findings. A White Paper of the ACR Incidental Findings Committee.

The ACR Incidental Findings Committee presents recommendations for managing incidentally detected lung findings on thoracic CT. The Chest Subcommittee is composed of thoracic radiologists who endorsed and developed the provided guidance. These recommendations represent a combination of current published evidence and expert opinion and were finalized by informal iterative consensus.

Nanobodies for Medical Imaging: About Ready for Prime Time?

Recent advances in medical treatments have been revolutionary in shaping the management and treatment landscape of patients, notably cancer patients. Over the last decade, patients with diverse forms of locally advanced or metastatic cancer, such as melanoma, lung cancers, and many blood-borne malignancies, have seen their life expectancies increasing significantly. Notwithstanding these encouraging results, the present-day struggle with these treatments concerns patients who remain largely unresponsive, as well as those who experience severely toxic side effects.

Use of a Dual Artificial Intelligence Platform to Detect Unreported Lung Nodules.

Objective: To investigate the performance of Dual-AI Deep Learning Platform in detecting unreported pulmonary nodules that are 6 mm or greater, comprising computer-vision (CV) algorithm to detect pulmonary nodules, with positive results filtered by natural language processing (NLP) analysis of the dictated report.

Methods: Retrospective analysis of 5047 chest CT scans and corresponding reports. Cases which were both CV algorithm positive (nodule ≥ 6 mm) and NLP negative (nodule not reported), were outputted for review by 2 chest radiologists.

FuncPEP: A Database of Functional Peptides Encoded by Non-Coding RNAs.

Non-coding RNAs (ncRNAs) are essential players in many cellular processes, from normal development to oncogenic transformation. Initially, ncRNAs were defined as transcripts that lacked an open reading frame (ORF). However, multiple lines of evidence suggest that certain ncRNAs encode small peptides of less than 100 amino acids.

A New World of Biomarkers and Therapeutics for Female Reproductive System and Breast Cancers: Circular RNAs.

As one of the most recently (re)discovered types of non-coding RNAs (ncRNA), circular RNAs (circRNAs) differentiate from other ncRNAs by a specific biogenesis, high stability, and distinct functions. The biogenesis of circRNAs can be categorized into three mechanisms that permit the back-splicing reaction: exon-skipping, pairing of neighboring introns, and dimerization of RNA-binding proteins. Regarding their stability, circRNAs have no free ends, specific to linear RNA molecules, prompting a longer half-life and resistance to exonuclease-mediated activity by RNase R, bypassing the common RNA turnover process.

Management of Incidental Adnexal Findings on CT and MRI: A White Paper of the ACR Incidental Findings Committee.

The ACR Incidental Findings Committee (IFC) presents recommendations for managing adnexal masses incidentally detected on CT and MRI. These recommendations represent an update of those provided in our previous JACR 2013 white paper. The Adnexal Subcommittee, which included six radiologists with subspecialty expertise in abdominal imaging or ultrasound and one gynecologist, developed this algorithm.

Diagnostic Radiologists' Participation in the American Board of Radiology Maintenance of Certification Program.

Physicians across specialties have expressed concerns about Maintenance of Certification (MOC) programs of American Board of Medical Specialties member boards, calling for research about MOC acceptance, adoption, and value. The purpose of this study was to characterize diagnostic radiologists' participation in the American Board of Radiology (ABR) MOC program, the framework for its new Online Longitudinal Assessment program. Practicing U.

Relationships Between Health Care Disparities and Coverage Policies for Breast, Colon, and Lung Cancer Screening.

Disparities in outcomes exist for breast, colon, and lung cancer among diverse populations, particularly racial and ethnic underrepresented minorities (URMs) and individuals from lower socioeconomic status. For example, blacks experience mortality rates up to about 42% higher than whites for these cancers. Furthermore, although overall death rates have been declining, the differential access to screening and care has aggravated disparities.

Multiplexed Immunohistochemistry for Molecular and Immune Profiling in Lung Cancer-Just About Ready for Prime-Time?

As targeted molecular therapies and immuno-oncology have become pivotal in the management of patients with lung cancer, the essential requirement for high throughput analyses and clinical validation of biomarkers has become even more intense, with response rates maintained in the 20%⁻30% range. Moreover, the list of treatment alternatives, including combination therapies, is rapidly evolving. The molecular profiling and specific tumor-associated immune contexture may be predictive of response or resistance to these therapeutic strategies.

Current views on tumor mutational burden in patients with non-small cell lung cancer treated by immune checkpoint inhibitors.

In the last few years, the treatment of patients with non-small cell lung cancer (NSCLC) has impressively benefitted from immunotherapy, in particular from the inhibition of immune checkpoints such as programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1). However, despite the significant survival benefit for some patients with advanced NSCLC, the objective response rates (ORRs) remain relatively low no more than 20-30% with a large proportion of patients demonstrating primary resistance. Although the selection of NSCLC patients for the first-line treatment is currently guided by the expression of PD-L1 in tumor cells as detected by immunohistochemistry, this is not the case for the second-line setting.