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Although the proteins BAX and BAK are required for initiation of apoptosis at the mitochondria, how BAX and BAK are activated remains unsettled. We provide in viva evidence demonstrating an essential role of the proteins BID, BIM, and PUMA in activating BAX and BAK. Bid, Bim, and Puma triple-knockout mice showed the same developmental defects that are associated with deficiency of Bax and Bak, including persistent interdigital webs and imperforate vaginas. Genetic deletion of Bid, Bim, and Puma prevented the homo-oligomerization of BAX and BAK, and thereby cytochrome c--mediated activation of caspases in response to diverse death signals in neurons and T lymphocytes, despite the presence of other BH3-only molecules. Thus, many forms of apoptosis require direct activation of BAX and BAK at the mitochondria by a member of the BID, BIM, or PUMA ramify of proteins. 10.1126/science.1190217

Objective: To identify factors associated with delayed adherence to follow-up in lung cancer screening. Methods: Utilizing a data warehouse and lung cancer screening registry, variables were collected from a referred sample of 3110 unique participants with follow-up CT during the study period (1 January 2016 to 17 October 2018). Adherence was defined as undergoing chest CT within 90 days and 30 days of the recommended time for follow-up and was determined using proportions and multiple variable logistic regression models across the American College of Radiology Lung Imaging Reporting and Data System (Lung-RADS®) categories. Results: Of 1954 lung cancer screening participants (51.9% (1014/1954) males, 48.1% (940/1954) female; mean age 65.7 (range 45–87), smoking history median 40 pack-years, 60.2% and 44.5% did not follow-up within 30 and 90 days, respectively. Participants receiving Lung-RADS® category 1 or 2 presented later than those with Lung-RADS® category 3 at 90 days (coefficient −27.24, 95% CI −51.31, −3.16, p = 0.027). Participants with Lung-RADS® category 1 presented later than those with Lung-RADS® category 2 at both 90- and 30-days past due (OR 0.76 95% CI [0.59–0.97], p = 0.029 and OR 0.63 95% CI [0.48–0.83], p = 0.001, respectively). Conclusions: Adherence to follow-up was higher among participants receiving more suspicious Lung-RADS® results at index screening CT and among those who had undergone more non-lung cancer screening imaging examinations prior to index lung cancer screening CT. These observations may inform strategies aimed at prospectively identifying participants at risk for delayed or nonadherence to prevent potential morbidity and mortality from incident lung cancers. [ABSTRACT FROM AUTHOR]

Three forms of cell death have been described: apoptosis, autophagic cell death, and necrosis. Although genetic and biochemical studies have formulated a detailed blueprint concerning the apoptotic network, necrosis is generally perceived as a passive cellular demise resulted from unmanageable physical damages. Here, we conclude an active de novo genetic program underlying DNA damage-induced necrosis, thus assigning necrotic cell death as a form of "programmed cell death." Cells deficient of the essential mitochondrial apoptotic effectors, BAX and BAK, ultimately succumbed to DNA damage, exhibiting signature necrotic characteristics. Importantly, this genotoxic stress-triggered necrosis was abrogated when either transcription or translation was inhibited. We pinpointed the p53-cathepsin axis as the quintessential framework underlying necrotic cell death. p53 induces cathepsin Q that cooperates with reactive oxygen species (ROS) to execute necrosis. Moreover, we presented the in vivo evidence of p53-activated necrosis in tumor allografts. Current study lays the foundation for future experimental and therapeutic discoveries aimed at "programmed necrotic death." [ABSTRACT FROM AUTHOR]

Although the proteins BAX and BAK are required for initiation of apoptosis at the mitochondria, how BAX and BAK are activated remains unsettled. We provide in vivo evidence demonstrating an essential role of the proteins BID, BIM, and PUMA in activating BAX and BAK. Bid, Bim, and Puma triple-knockout mice showed the same developmental defects that are associated with deficiency of Bax and Bak, including persistent interdigital webs and imperforate vaginas. Genetic deletion of Bid, Birn, and Puma prevented the homo-oligomerization of BAX and BAK, and thereby cytochrome c-mediated activation of caspases in response to diverse death signals in neurons and T lymphocytes, despite the presence of other BH3-only molecules. Thus, many forms of apoptosis require direct activation of BAX and BAK at the mitochondria by a member of the BID, BIM, or PUMA family of proteins. [ABSTRACT FROM AUTHOR]

BACKGROUND. Screening mammography facilities closed during the COVID-19 pandemic in spring 2020. Recovery of screening volumes has varied across patient subgroups and facilities. OBJECTIVE. We compared screening mammography volumes and patient and facility characteristics between periods before COVID-19 and early and later postclosure recovery periods. METHODS. This retrospective study included screening mammograms performed in the same 2-month period (May 26-July 26) in 2019 (pre-COVID-19), 2020 (early recovery), and 2021 (late recovery after targeted interventions to expand access) and across multiple facility types (urban, suburban, community health center). Suburban sites had highest proportion of White patients and the greatest scheduling flexibility and expanded appointments during initial reopening. Findings were compared across years. RESULTS. For White patients, volumes decreased 36.6% from 6550 in 2019 (4384 in 2020) and then increased 61.0% to 6579 in 2021; for patients with races other than White, volumes decreased 53.9% from 1321 in 2019 (609 in 2020) and then increased 136.8% to 1442 in 2021. The percentage of mammograms in patients with races other than White was 16.8% in 2019, 12.2% in 2020, and 18.0% in 2021. The proportion performed at the urban center was 55.3% in 2019, 42.2% in 2020, and 45.9% in 2021; the proportion at suburban sites was 34.0% in 2019, 49.2% in 2020, and 43.5% in 2021. Pre-COVID-19 volumes were reached by the sixth week after reopening for suburban sites but were not reached during early recovery for the other sites. The proportion that were performed on Saturday for suburban sites was similar across periods, whereas the proportion performed on Saturday for the urban site was 7.6% in 2019, 5.3% in 2020, and 8.8% in 2021; the community health center did not offer Saturday appointments during recovery. CONCLUSION. After reopening, screening shifted from urban to suburban settings, with a disproportionate screening decrease in patients with races other than White. Initial delayed access at facilities serving underserved populations exacerbated disparities. Interventions to expand access resulted in late recovery volumes exceeding prepandemic volumes in patients with races other than White. CLINICAL IMPACT. Interventions to support equitable access across facilities serving diverse patient populations may mitigate potential widening disparities in breast cancer diagnosis during the pandemic.

BACKGROUND. The need for second visits between screening mammography and diagnostic imaging contributes to disparities in the time to breast cancer diagnosis. During the COVID-19 pandemic, an immediate-read screening mammography program was implemented to reduce patient visits and decrease time to diagnostic imaging. OBJECTIVE. The purpose of this study was to measure the impact of an immediate-read screening program with focus on disparities in same-day diagnostic imaging after abnormal findings are made at screening mammography. METHODS. In May 2020, an immediate-read screening program was implemented whereby a dedicated breast imaging radiologist interpreted all screening mammograms in real time; patients received results before discharge; and efforts were made to perform any recommended diagnostic imaging during the visit (performed by different radiologists). Screening mammographic examinations performed from June 1, 2019, through October 31, 2019 (preimplementation period), and from June 1, 2020, through October 31, 2020 (postimplementation period), were retrospectively identified. Patient characteristics were recorded from the electronic medical record. Multivariable logistic regression models incorporating patient age, race and ethnicity, language, and insurance type were estimated to identify factors associated with same-day diagnostic imaging. Screening metrics were compared between periods. RESULTS. A total of 8222 preimplementation and 7235 postimplementation screening examinations were included; 521 patients had abnormal screening findings before implementation, and 359 after implementation. Before implementation, 14.8% of patients underwent same-day diagnostic imaging after abnormal screening mammograms. This percentage increased to 60.7% after implementation. Before implementation, patients who identified their race as other than White had significantly lower odds than patients who identified their race as White of undergoing same-day diagnostic imaging after receiving abnormal screening results (adjusted odds ratio, 0.30; 95% CI, 0.10-0.86; p = .03). After implementation, the odds of same-day diagnostic imaging were not significantly different between patients of other races and White patients (adjusted odds ratio, 0.92; 95% CI, 0.50-1.71; p = .80). After implementation, there was no significant difference in race and ethnicity between patients who underwent and those who did not undergo same-day diagnostic imaging after receiving abnormal results of screening mammography ( p > .05). The rate of abnormal interpretation was significantly lower after than it was before implementation (5.0% vs 6.3%; p < .001). Cancer detection rate and PPV1 (PPV based on positive findings at screening examination) were not significantly different before and after implementation ( p > .05). CONCLUSION. Implementation of the immediate-read screening mammography program reduced prior racial and ethnic disparities in same-day diagnostic imaging after abnormal screening mammograms. CLINICAL IMPACT. An immediate-read screening program provides a new paradigm for improved screening mammography workflow that allows more rapid diagnostic workup with reduced disparities in care.

Objective: The purpose of this article is to review the mechanisms of action of immune checkpoint inhibitors in the treatment of non-small cell lung cancer (NSCLC), highlight imaging manifestations of common adverse events, and discuss new criteria for using imaging to assess unique treatment response patterns., Conclusion: Immune checkpoint inhibitor therapy is a breakthrough in cancer treatment that has shown unprecedented success when used for a variety of malignancies. In recent phase 3 clinical trials for NSCLC, monoclonal antibodies that target the programmed death-1 (PD-1) receptor and its ligand PD-L1 (i.e., the PD-1/PD-L1 axis) were associated with better overall survival in head-to-head comparisons with conventional cytotoxic chemotherapy. On the strength of the results of these trials, the PD-1 inhibitors nivolumab and pembrolizumab and the PD-L1 inhibitor atezolizumab recently received regulatory approval by the U.S. Food and Drug Administration for the treatment of advanced NSCLC. Because of their unique mechanisms of action, these agents differ from conventional cytotoxic chemotherapy in both patterns of treatment response and treatment-related adverse events. Given the rapidly expanding clinical use of immune checkpoint inhibitors and the central role of radiology in the care of patients with lung cancer, it is important for radiologists to be familiar with these agents and their unique imaging findings.