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Aim: These are extraordinary times caused by the first global pandemic in our modern era. Physicians and other frontline healthcare providers face unique challenges, for which they have had little formal preparation. This combination of challenge and deficit leads to significant negative impacts, not only on what medical practices and health care systems can deliver to the public, but also on the individual healthcare providers themselves. Methods: In this essay, we specifically address women physicians, and explore the considerable impact they bear from the COVID-19 pandemic, particularly in the contexts of response to stress, social isolation, work-life integration, and autonomy. Because the language we use is important, we think it necessary to clarify that when we refer to 'women physicians,' we are referring to physicians that self-identify as women, and we acknowledge that not all the references we cite may use the same definition. Results: We offer several potential interventions that turn the challenges women physicians are facing into opportunities to address longstanding inequity. These interventions include tackling barriers to work-life balance, addressing gender and maternal bias, and promoting women physician representation in leadership. Conclusion: The COVID-19 pandemic is likely to become a chronic part of our lives; protecting vulnerable populations, such as women physicians, through thoughtful intervention is paramount. Women physicians experience considerable adversity during the COVID-19 pandemic, particularly in the contexts of response to stress, social isolation, work-life integration, and autonomy. These challenges create opportunities for interventions to improve equity in medicine during the COVID-19 pandemic and in the long-term, including tackling barriers to work-life balance, addressing gender and maternal bias, and promoting women physician representation in leadership. [ABSTRACT FROM AUTHOR]

Objective: The present study aimed to investigate the intermediary role of distress tolerance in Mindfulness-Based Intervention (MBI) with respect to self-perceived stress reduction. Method: One hundred and twenty-nine adults with a high level of emotional distress were randomized into MBI groups or a waiting-list group. Levels of mindfulness skills, self-perceived stress, and distress tolerance (tolerance, appraisal, absorption, and regulation) were measured four times: pre-test, week 3, week 6, and post-test. Results: The developmental trajectories modeled by the univariate latent growth curve showed that the factor intervention significantly predicted the slope of observing, non-reactivity, overall mindfulness, and distress appraisal during first six weeks. Bivariate latent growth curve models demonstrated a significant association between increases in the growth rate of distress appraisal and non-reactivity in participants receiving mindfulness training. Such an association was not observed among those who did not receive an MBI. Longitudinal mediation analyses further revealed that the effect of MBI on non-reactivity and self-perceived stress at week 6 was fully mediated by distress appraisal at week 3, respectively. Conclusions: Our results indicate that distress appraisal plays an important role during the earlier stage of MBI, which might contribute to a more effective and efficient intervention program in the future. [ABSTRACT FROM AUTHOR]

1. Participants will identify knowledge about immunotherapy as an important educational target for adults with advanced cancer that may be addressed through a video and question prompt list intervention. 2. Participants will be able to appraise the feasibility of one approach to improving patient and caregiver knowledge about immunotherapy for advanced cancer. Immunotherapy has revolutionized cancer treatment and causes novel toxicities that are important for patients to understand. We developed a video and question prompt list intervention to educate patients about immunotherapy. In a randomized controlled trial, we found that the intervention was feasible to deliver, acceptable, and improved immunotherapy knowledge versus usual care among adults with advanced cancer, without increasing anxiety. Immune checkpoint inhibitors (ICIs) improve cancer survival and cause novel toxicities. We developed UPLIFT (Understanding and Preparing for Life on Immunotherapy), an educational video and question prompt list (QPL) intervention for adults initiating ICIs. To test the feasibility and acceptability of UPLIFT and its effects on immunotherapy knowledge and anxiety. We conducted a pilot randomized controlled trial (NCT04670445) of UPLIFT among adults initiating an ICI for advanced cancer. Participants were randomized 1:1 to receive UPLIFT prior to ICI initiation or usual care. Participants completed surveys at enrollment (baseline), within 72 hours after ICI initiation (72h), and at 6 weeks. The primary outcome was feasibility (70% enrollment among approached patients and 80% video completion and QPL review). We also assessed acceptability, immunotherapy knowledge (8-item survey, scored as % correct), and anxiety (State and Trait Anxiety Index-Short Form). We used ANCOVA models to analyze knowledge and anxiety outcomes. We enrolled 130 of 178 approached, eligible patients (73%). 66 patients were randomized to receive UPLIFT and 65 to control. Patients (38% female, mean age=67y) had diagnoses of melanoma (40%), lung cancer (26%), or other cancers (34%). All 66 (100%) patients assigned to UPLIFT watched the video and received the QPL. 94% of patients were "somewhat" or "very comfortable" with UPLIFT. Immunotherapy knowledge improved from baseline to 72h among patients assigned to UPLIFT relative to control (difference in adjusted mean % correct: 9% [95% CI: 3% - 16%]). The change in anxiety from baseline to 72h did not significantly differ between groups (0.6, 95% CI: -2.6 - 3.8). There were no between-group differences in knowledge or anxiety score change from baseline to 6 weeks. A novel educational intervention was feasible to deliver, acceptable, and improved immunotherapy knowledge relative to usual care among adults with advanced cancer, without increasing anxiety. Communication / Disease specific management [ABSTRACT FROM AUTHOR]

Purpose: Immunotherapy has improved survival for patients with melanoma and non-small cell lung cancer (NSCLC). Yet, as responses vary widely, immunotherapy also introduces challenges in prognostic communication. In this study, we sought to explore how patients and caregivers learned about the goal of immunotherapy and their experience of living with uncertainty., Materials and Methods: We conducted a qualitative study of patients with stage III or IV melanoma or stage IV NSCLC within 12 weeks of initiating or 12 months of discontinuing immunotherapy, and their caregivers. We conducted in-depth interviews with participants to explore how they learned about immunotherapy from oncology clinicians and how they experienced uncertainty. We used a framework approach to analyze interview transcripts and synthesized concepts into themes., Results: Forty-two patients and 10 caregivers participated; median age was 67 years and most were male (68%), white (95%), married (61%), and had melanoma (62%). We identified four themes: (1) the oncology team shaped participants' hopeful expectations of immunotherapy, including as a potential cure among those with melanoma; (2) distress related to prognostic uncertainty particularly affected patients who experienced toxicity or progressive disease; (3) patients who did not have long-term responses experienced overwhelming disappointment; and (4) some patients and caregivers had conflicting preferences for prognostic information. Participants provided suggestions to improve education and underscored unmet psychosocial needs., Conclusion: Patients and caregivers held optimistic expectations of immunotherapy, which resulted in heightened disappointment among the subset with progression or toxicity. Clinicians should elicit information preferences of both patients and caregivers, as these may be disparate. Our results highlight the need to optimize prognostic communication and support for living with uncertainty among patients receiving immunotherapy.

Oncogenic KRAS (KRAS*) contributes to many cancer hallmarks. In colorectal cancer, KRAS* suppresses antitumor immunity to promote tumor invasion and metastasis. Here, we uncovered that KRAS* transforms the phenotype of carcinoma-associated fibroblasts (CAF) into lipid-laden CAFs, promoting angiogenesis and tumor progression. Mechanistically, KRAS* activates the transcription factor CP2 (TFCP2) that upregulates the expression of the proadipogenic factors BMP4 and WNT5B, triggering the transformation of CAFs into lipid-rich CAFs. These lipid-rich CAFs, in turn, produce VEGFA to spur angiogenesis. In KRAS*-driven colorectal cancer mouse models, genetic or pharmacologic neutralization of TFCP2 reduced lipid-rich CAFs, lessened tumor angiogenesis, and improved overall survival. Correspondingly, in human colorectal cancer, lipid-rich CAF and TFCP2 signatures correlate with worse prognosis. This work unveils a new role for KRAS* in transforming CAFs, driving tumor angiogenesis and disease progression, providing an actionable therapeutic intervention for KRAS*-driven colorectal cancer., Significance: This study identified a molecular mechanism contributing to KRAS*-driven colorectal cancer progression via fibroblast transformation in the tumor microenvironment to produce VEGFA driving tumor angiogenesis. In preclinical models, targeting the KRAS*-TFCP2-VEGFA axis impaired tumor progression, revealing a potential novel therapeutic option for patients with KRAS*-driven colorectal cancer. This article is featured in Selected Articles from This Issue, p. 2489., (©2023 American Association for Cancer Research.)

Since the development of CRISPR/Cas9 gene editing in 2012, therapeutic editing research has produced several phase 1-2a trials. Here we provide an overview of the mechanisms and applications of various gene-editing technologies including adeno-associated virus vectors, lentiviruses, CRISPR/Cas9 systems, base and prime editing, antisense oligonucleotides, short-hairpin RNAs, Cas13, and adenosine deaminase acting on RNA for the treatment of various inherited retinal diseases (IRDs). We outline the various stages of clinical trials using these technologies and the impacts they have made in advancing the practice of medicine., (Copyright © 2023 Cold Spring Harbor Laboratory Press; all rights reserved.)