The use of coaching in smartphone app-based cognitive behavioral therapy for body dysmorphic disorder.

Background: Body dysmorphic disorder (BDD) is severe and undertreated. Digital mental health could be key to expanding access to evidence-based treatments, such as cognitive behavioral therapy for BDD (CBT-BDD). Coach guidance is posited to be essential for effective uptake of digital interventions. However, little is known about how different patients may use coaching, what patterns correspond to meaningful outcomes, and how to match coaching to patient needs. Methods: Participants were 77 adults who received a 12-week guided smartphone CBT-BDD. Bachelor's-level coaches were available via asynchronous messaging. We analyzed the 400 messages sent by users to coaches during treatment. Message content was coded using the efficiency model of support (i.e., usability, engagement, fit, knowledge, and implementation). We aimed to clarify when and for what purposes patients with BDD used coaching, and if we can meaningfully classify patients by these patterns. We then assessed potential baseline predictors of coach usage, and whether distinct patterns relate to clinical outcomes. Results: Users on average sent 5.88 messages (SD = 4.51, range 1-20) and received 9.84 (SD = 5.74, range 2-30). Regarding frequency of sending messages, latent profile analysis revealed three profiles, characterized by: (1) peak mid-treatment (16.88 %), (2) bimodal/more communication early and late in treatment (10.39 %), and (3) consistent low/no communication (72.73 %). Regarding content, four profiles emerged, characterized by mostly (1) engagement (51.95 %), (2) fit (15.58 %), (3) knowledge (15.58 %), and (4) miscellaneous/no messages (16.88 %). There was a significant relationship between frequency profile and age, such that the early/late peak group was older than the low communication group, and frequency profile and adherence, driven by the mid-treatment peak group completing more modules than the low contact group. Regarding content, the engagement and knowledge groups began treatment with more severe baseline symptoms than the fit group. Content profile was associated with dropout, suggesting higher dropout rates in the miscellaneous/no contact group and reduced rates in the engagement group. There was no relationship between profile membership and other outcomes. Discussion: The majority of participants initiated little contact with their coach and the most common function of communications was to increase engagement. Results suggest that older individuals may prefer or require more support than younger counterparts early in treatment. Additionally, whereas individuals using coaching primarily for engagement may be at lower risk of dropping out, those who do not engage at all may be at elevated risk. Findings can support more personalized, data-driven coaching protocols and more efficient allocation of coaching resources.

Feasibility, Acceptability, and Preliminary Efficacy of a Smartphone App-Led Cognitive Behavioral Therapy for Depression Under Therapist Supervision: Open Trial.

BACKGROUND: Major depressive disorder affects approximately 1 in 5 adults during their lifetime and is the leading cause of disability worldwide. Yet, a minority receive adequate treatment due to person-level (eg, geographical distance to providers) and systems-level (eg, shortage of trained providers) barriers. Digital tools could improve this treatment gap by reducing the time and frequency of therapy sessions needed for effective treatment through the provision of flexible, automated support. OBJECTIVE: This study aimed to examine the feasibility, acceptability, and preliminary clinical effect of Mindset for Depression, a deployment-ready 8-week smartphone-based cognitive behavioral therapy (CBT) supported by brief teletherapy appointments with a therapist. METHODS: This 8-week, single-arm open trial tested the Mindset for Depression app when combined with 8 brief (16-25 minutes) video conferencing visits with a licensed doctoral-level CBT therapist (n=28 participants). The app offers flexible, accessible psychoeducation, CBT skills practice, and support to patients as well as clinician guidance to promote sustained engagement, monitor safety, and tailor treatment to individual patient needs. To increase accessibility and thus generalizability, all study procedures were conducted remotely. Feasibility and acceptability were assessed via attrition, patient expectations and feedback, and treatment utilization. The primary clinical outcome measure was the clinician-rated Hamilton Depression Rating Scale, administered at pretreatment, midpoint, and posttreatment. Secondary measures of functional impairment and quality of life as well as maintenance of gains (3-month follow-up) were also collected. RESULTS: Treatment credibility (week 4), expectancy (week 4), and satisfaction (week 8) were moderate to high, and attrition was low (n=2, 7%). Participants self-reported using the app or practicing (either on or off the app) the CBT skills taught in the app for a median of 50 (IQR 30-60; week 4) or 60 (IQR 30-90; week 8) minutes per week; participants accessed the app on an average 36.8 (SD 10.0) days and completed a median of 7 of 8 (IQR 6-8) steps by the week 8 assessment. The app was rated positively across domains of engagement, functionality, aesthetics, and information. Participants' depression severity scores decreased from an average Hamilton Depression Rating Scale score indicating moderate depression (mean 19.1, SD 5.0) at baseline to a week 8 mean score indicating mild depression (mean 10.8, SD 6.1; d=1.47; P<.001). Improvement was also observed for functional impairment and quality of life. Gains were maintained at 3-month follow-up. CONCLUSIONS: The results show that Mindset for Depression is a feasible and acceptable treatment option for individuals with major depressive disorder. This smartphone-led treatment holds promise to be an efficacious, scalable, and cost-effective treatment option. The next steps include testing Mindset for Depression in a fully powered randomized controlled trial and real-world clinical settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT05386329; https://clinicaltrials.gov/study/NCT05386329?term=NCT05386329.

Lessons and Untapped Potential of Smartphone-Based Physical Activity Interventions for Mental Health: Narrative Review.

BACKGROUND: Physical activity has well-known and broad health benefits, including antidepressive and anxiolytic effects. However, only approximately half of Americans meet even the minimum exercise recommendations. Individuals with anxiety, depression, or related conditions are even less likely to do so. With the advent of mobile sensors and phones, experts have quickly noted the utility of technology for the enhanced measurement of and intervention for physical activity. In addition to being more accessible than in-person approaches, technology-driven interventions may uniquely engage key mechanisms of behavior change such as self-awareness. OBJECTIVE: This study aims to provide a narrative overview and specific recommendations for future research on smartphone-based physical activity interventions for psychological disorders or concerns. METHODS: In this paper, we summarized early efforts to adapt and test smartphone-based or smartphone-supported physical activity interventions for mental health. The included articles described or reported smartphone-delivered or smartphone-supported interventions intended to increase physical activity or reduce sedentary behavior and included an emotional disorder, concern, or symptom as an outcome measure. We attempted to extract details regarding the intervention designs, trial designs, study populations, outcome measures, and inclusion of adaptations specifically for mental health. In taking a narrative lens, we drew attention to the type of work that has been done and used these exemplars to discuss key directions to build on. RESULTS: To date, most studies have examined mental health outcomes as secondary or exploratory variables largely in the context of managing medical concerns (eg, cancer and diabetes). Few trials have recruited psychiatric populations or explicitly aimed to target psychiatric concerns. Consequently, although there are encouraging signals that smartphone-based physical activity interventions could be feasible, acceptable, and efficacious for individuals with mental illnesses, this remains an underexplored area. CONCLUSIONS: Promising avenues for tailoring validated smartphone-based interventions include adding psychoeducation (eg, the relationship between depression, physical activity, and inactivity), offering psychosocial treatment in parallel (eg, cognitive restructuring), and adding personalized coaching. To conclude, we offer specific recommendations for future research, treatment development, and implementation in this area, which remains open and promising for flexible, highly scalable support.

Differential histone acetylation and super-enhancer regulation underlie melanoma cell dedifferentiation.

Dedifferentiation or phenotype switching refers to the transition from a proliferative to an invasive cellular state. We previously identified a 122-gene epigenetic gene signature that classifies primary melanomas as low versus high risk (denoted as Epgn1 or Epgn3). We found that the transcriptomes of the Epgn1 low-risk and Epgn3 high-risk cells are similar to the proliferative and invasive cellular states, respectively. These signatures were further validated in melanoma tumor samples. Examination of the chromatin landscape revealed differential H3K27 acetylation in the Epgn1 low-risk versus Epgn3 high-risk cell lines that corroborated with a differential super-enhancer and enhancer landscape. Melanocytic lineage genes (MITF, its targets and regulators) were associated with super-enhancers in the Epgn1 low-risk state, whereas invasiveness genes were linked with Epgn3 high-risk status. We identified the ITGA3 gene as marked by a super-enhancer element in the Epgn3 invasive cells. Silencing of ITGA3 enhanced invasiveness in both in vitro and in vivo systems, suggesting it as a negative regulator of invasion. In conclusion, we define chromatin landscape changes associated with Epgn1/Epgn3 and phenotype switching during early steps of melanoma progression that regulate transcriptional reprogramming. This super-enhancer and enhancer-driven epigenetic regulatory mechanism resulting in major changes in the transcriptome could be important in future therapeutic targeting efforts.

A roadmap to address stress in graduate students: How to develop and disseminate a student-led single-session evidence based intervention.

Objective: This manuscript describes an evidence-based, student-led, single-session group intervention to support emotional wellbeing among graduate students. The present objective is to provide a roadmap for other universities. Participants: Key participants include clinical psychology graduate students (leader and workshop facilitators), faculty supervisor, representatives from receiving departments or schools, and institutional advocates. Methods: The two-hour workshop was based on four core transdiagnostic cognitive behavioral skills, including psychoeducation about emotions, mindful emotional awareness, cognitive flexibility, and behavior change. The workshop was designed and continues to be led by trained graduate students. Results: Key steps and lessons learned are presented for the exploration, preparation, implementation, and sustainment phases. Conclusions: This program has the potential to be flexibly replicated at other universities to assist with graduate student mental health. It provides unique supports for recipients and unique training opportunities for student facilitators.

Impact of sleep disruption on BDD symptoms and treatment response.

BACKGROUND: Body dysmorphic disorder (BDD) is severe, undertreated, and relatively common. Although gold-standard cognitive behavioral therapy (CBT) for BDD has strong empirical support, a significant number of patients do not respond. More work is needed to understand BDD's etiology and modifiable barriers to treatment response. Given its high prevalence and impact on the development, maintenance, and treatment of related, frequently comorbid disorders, sleep disruption is a compelling, but not-yet studied factor. METHODS: Data were drawn from a randomized controlled trial of guided smartphone app-based CBT for BDD. Included participants were offered 12-weeks of treatment, immediately (n = 40) or after a 12-week waitlist (n = 37). Sleep disruption and BDD symptom severity were assessed at baseline, week-6, and week-12. RESULTS: Hypotheses and analysis plan were pre-registered. Two-thirds of patients reported significant insomnia symptoms at baseline. Baseline severity of sleep disruption and BDD symptoms were not related (r = 0.02). Pre-treatment sleep disruption did not predict BDD symptom reduction across treatment, nor did early sleep improvements predict greater BDD symptom improvement. Early BDD symptom improvement also did not predict later improvements in sleep. LIMITATIONS: Limitations include the small sample, restricted ranges of BDD symptom severity and treatment response, and few metrics of sleep disruption. CONCLUSIONS: Although insomnia was disproportionately high in this sample and both BDD symptoms and sleep improved in treatment, results suggest sleep and BDD symptoms may function largely independent of one another. More work is encouraged to replicate and better understand findings as well as potential challenges and benefits of addressing sleep in BDD.

H2A.Z chaperones converge on histone H4 acetylation for melanoma cell proliferation.

High levels of H2A.Z promote melanoma cell proliferation and correlate with poor prognosis. However, the role of the two distinct H2A.Z histone chaperone complexes, SRCAP and P400-TIP60, in melanoma remains unclear. Here, we show that individual depletion of SRCAP, P400, and VPS72 (YL1) not only results in loss of H2A.Z deposition into chromatin, but also a striking reduction of H4 acetylation in melanoma cells. This loss of H4 acetylation is found at the promoters of cell cycle genes directly bound by H2A.Z and its chaperones, suggesting a highly coordinated regulation between H2A.Z deposition and H4 acetylation to promote their expression. Knockdown of each of the three subunits downregulates E2F1 and its targets, resulting in a cell cycle arrest akin to H2A.Z depletion. However, unlike H2A.Z deficiency, loss of the shared H2A.Z chaperone subunit YL1 induces apoptosis. Furthermore, YL1 is overexpressed in melanoma tissues, and its upregulation is associated with poor patient outcome. Together, these findings provide a rationale for future targeting of H2A.Z chaperones as an epigenetic strategy for melanoma treatment.

LKB1-SIK2 loss drives uveal melanoma proliferation and hypersensitivity to SLC8A1 and ROS inhibition.

Metastatic uveal melanomas are highly resistant to all existing treatments. To address this critical issue, we performed a kinome-wide CRISPR-Cas9 knockout screen, which revealed the LKB1-SIK2 module in restraining uveal melanoma tumorigenesis. Functionally, LKB1 loss enhances proliferation and survival through SIK2 inhibition and upregulation of the sodium/calcium (Na+ /Ca2+ ) exchanger SLC8A1. This signaling cascade promotes increased levels of intracellular calcium and mitochondrial reactive oxygen species, two hallmarks of cancer. We further demonstrate that combination of an SLC8A1 inhibitor and a mitochondria-targeted antioxidant promotes enhanced cell death efficacy in LKB1- and SIK2-negative uveal melanoma cells compared to control cells. Our study also identified an LKB1-loss gene signature for the survival prognostic of patients with uveal melanoma that may be also predictive of response to the therapy combination. Our data thus identify not only metabolic vulnerabilities but also new prognostic markers, thereby providing a therapeutic strategy for particular subtypes of metastatic uveal melanoma.

Sustained CD28 costimulation is required for self-renewal and differentiation of TCF-1+ PD-1+ CD8 T cells.

During persistent antigen stimulation, such as in chronic infections and cancer, CD8 T cells differentiate into a hypofunctional programmed death protein 1-positive (PD-1+) exhausted state. Exhausted CD8 T cell responses are maintained by precursors (Tpex) that express the transcription factor T cell factor 1 (TCF-1) and high levels of the costimulatory molecule CD28. Here, we demonstrate that sustained CD28 costimulation is required for maintenance of antiviral T cells during chronic infection. Low-level CD28 engagement preserved mitochondrial fitness and self-renewal of Tpex, whereas stronger CD28 signaling enhanced glycolysis and promoted Tpex differentiation into TCF-1neg exhausted CD8 T cells (Tex). Furthermore, enhanced differentiation by CD28 engagement did not reduce the Tpex pool. Together, these findings demonstrate that continuous CD28 engagement is needed to sustain PD-1+ CD8 T cells and suggest that increasing CD28 signaling promotes Tpex differentiation into more functional effector-like Tex, possibly without compromising long-term responses.

MacroH2A restricts inflammatory gene expression in melanoma cancer-associated fibroblasts by coordinating chromatin looping.

MacroH2A has established tumour suppressive functions in melanoma and other cancers, but an unappreciated role in the tumour microenvironment. Using an autochthonous, immunocompetent mouse model of melanoma, we demonstrate that mice devoid of macroH2A variants exhibit increased tumour burden compared with wild-type counterparts. MacroH2A-deficient tumours accumulate immunosuppressive monocytes and are depleted of functional cytotoxic T cells, characteristics consistent with a compromised anti-tumour response. Single cell and spatial transcriptomics identify increased dedifferentiation along the neural crest lineage of the tumour compartment and increased frequency and activation of cancer-associated fibroblasts following macroH2A loss. Mechanistically, macroH2A-deficient cancer-associated fibroblasts display increased myeloid chemoattractant activity as a consequence of hyperinducible expression of inflammatory genes, which is enforced by increased chromatin looping of their promoters to enhancers that gain H3K27ac. In summary, we reveal a tumour suppressive role for macroH2A variants through the regulation of chromatin architecture in the tumour stroma with potential implications for human melanoma.

5-Azacytidine- and retinoic-acid-induced reprogramming of DCCs into dormancy suppresses metastasis via restored TGF-ß-SMAD4 signaling.

Disseminated cancer cells (DCCs) in secondary organs can remain dormant for years to decades before reactivating into overt metastasis. Microenvironmental signals leading to cancer cell chromatin remodeling and transcriptional reprogramming appear to control onset and escape from dormancy. Here, we reveal that the therapeutic combination of the DNA methylation inhibitor 5-azacytidine (AZA) and the retinoic acid receptor ligands all-trans retinoic acid (atRA) or AM80, an RARα-specific agonist, promotes stable dormancy in cancer cells. Treatment of head and neck squamous cell carcinoma (HNSCC) or breast cancer cells with AZA+atRA induces a SMAD2/3/4-dependent transcriptional program that restores transforming growth factor ß (TGF-ß)-signaling and anti-proliferative function. Significantly, either combination, AZA+atRA or AZA+AM80, strongly suppresses HNSCC lung metastasis formation by inducing and maintaining solitary DCCs in a SMAD4+/NR2F1+ non-proliferative state. Notably, SMAD4 knockdown is sufficient to drive resistance to AZA+atRA-induced dormancy. We conclude that therapeutic doses of AZA and RAR agonists may induce and/or maintain dormancy and significantly limit metastasis development.

Mechanisms of cognitive-behavioral therapy effects on symptoms of body dysmorphic disorder: a network intervention analysis.

BACKGROUND: Body dysmorphic disorder (BDD) is a severe and undertreated condition. Although cognitive-behavioral therapy (CBT) is the first-line psychosocial treatment for this common disorder, how the intervention works is insufficiently understood. Specific pathways have been hypothesized, but only one small study has examined the precise nature of treatment effects of CBT, and no prior study has examined the effects of supportive psychotherapy (SPT). METHODS: This study re-examined a large trial (n = 120) comparing CBT to SPT for BDD. Network intervention analyses were used to explore symptom-level data across time. We computed mixed graphical models at multiple time points to examine relative differences in direct and indirect effects of the two interventions. RESULTS: In the resulting networks, CBT and SPT appeared to differentially target certain symptoms. The largest differences included CBT increasing efforts to disengage from and restructure unhelpful thoughts and resist BDD rituals, while SPT was directly related to improvement in BDD-related insight. Additionally, the time course of differences aligned with the intended targets of CBT; cognitive effects emerged first and behavioral effects second, paralleling cognitive restructuring in earlier sessions and the emphasis on exposure and ritual prevention in later sessions. Differences in favor of CBT were most consistent for behavioral targets. CONCLUSIONS: CBT and SPT primarily affected different symptoms. To improve patient care, the field needs a better understanding of how and when BDD treatments and treatment components succeed. Considering patient experiences at the symptom level and over time can aid in refining or reorganizing treatments to better fit patient needs.

Helpful for all? Examining the effects of psychotherapy treatment history on outcomes of single session, transdiagnostic cognitive behavioral interventions for university students.

Brief, transdiagnostic interventions are an efficient form of mental health care for resource-limited settings like universities. Little research, however, has examined for whom these treatments are most effective. One important factor may be psychotherapy treatment history. Here, we evaluate if treatment history influences the effects of a single-session cognitive behavioral group intervention with optional digital follow-up support across two independent, university-based studies. Undergraduate (N = 143) and graduate (N = 51) students reported their psychotherapy treatment history and completed self-report measures of emotional health before and approximately 1-month following the intervention. Across both samples, psychotherapy treatment history did not moderate changes in depression, anxiety, or emotional avoidance following the intervention. However, participants who were currently receiving psychotherapy began the workshop with lower coping self-efficacy than peers with no prior psychotherapy and saw larger gains in coping self-efficacy at follow-up. Results suggest that regardless of whether a student has previously received psychotherapy, they may benefit from brief, group transdiagnostic interventions. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

MacroH2A histone variants modulate enhancer activity to repress oncogenic programs and cellular reprogramming.

Considerable efforts have been made to characterize active enhancer elements, which can be annotated by accessible chromatin and H3 lysine 27 acetylation (H3K27ac). However, apart from poised enhancers that are observed in early stages of development and putative silencers, the functional significance of cis-regulatory elements lacking H3K27ac is poorly understood. Here we show that macroH2A histone variants mark a subset of enhancers in normal and cancer cells, which we coined 'macro-Bound Enhancers', that modulate enhancer activity. We find macroH2A variants localized at enhancer elements that are devoid of H3K27ac in a cell type-specific manner, indicating a role for macroH2A at inactive enhancers to maintain cell identity. In following, reactivation of macro-bound enhancers is associated with oncogenic programs in breast cancer and their repressive role is correlated with the activity of macroH2A2 as a negative regulator of BRD4 chromatin occupancy. Finally, through single cell epigenomic profiling of normal mammary stem cells derived from mice, we show that macroH2A deficiency facilitates increased activity of transcription factors associated with stem cell activity.

Predictors of pharmacotherapy outcomes for body dysmorphic disorder: a machine learning approach.

BACKGROUND: Serotonin-reuptake inhibitors (SRIs) are first-line pharmacotherapy for the treatment of body dysmorphic disorder (BDD), a common and severe disorder. However, prior research has not focused on or identified definitive predictors of SRI treatment outcomes. Leveraging precision medicine techniques such as machine learning can facilitate the prediction of treatment outcomes. METHODS: The study used 10-fold cross-validation support vector machine (SVM) learning models to predict three treatment outcomes (i.e. response, partial remission, and full remission) for 97 patients with BDD receiving up to 14-weeks of open-label treatment with the SRI escitalopram. SVM models used baseline clinical and demographic variables as predictors. Feature importance analyses complemented traditional SVM modeling to identify which variables most successfully predicted treatment response. RESULTS: SVM models indicated acceptable classification performance for predicting treatment response with an area under the curve (AUC) of 0.77 (sensitivity = 0.77 and specificity = 0.63), partial remission with an AUC of 0.75 (sensitivity = 0.67 and specificity = 0.73), and full remission with an AUC of 0.79 (sensitivity = 0.70 and specificity = 0.79). Feature importance analyses supported constructs such as better quality of life and less severe depression, general psychopathology symptoms, and hopelessness as more predictive of better treatment outcome; demographic variables were least predictive. CONCLUSIONS: The current study is the first to demonstrate that machine learning algorithms can successfully predict treatment outcomes for pharmacotherapy for BDD. Consistent with precision medicine initiatives in psychiatry, the current study provides a foundation for personalized pharmacotherapy strategies for patients with BDD.

Credibility and expectancy of smartphone-based cognitive behavioral therapy among adults with body dysmorphic disorder.

BACKGROUND: Few patients receive cognitive behavioral therapy, the gold-standard for body dysmorphic disorder (CBT-BDD). Smartphones can make evidence-based interventions, like CBT-BDD, more accessible and scalable. A key question is: how do patients view it? Low credibility and expectancy would likely translate to low uptake and engagement outside of research settings, diminishing the impact. Thus, it is important to understand patients' beliefs about digital CBT-BDD. METHODS: We compared credibility and expectancy in a coach-guided app-based CBT-BDD trial (N=75) to a previous in-person CBT-BDD trial (N = 55). We further examined the relationship of perceptions of digital CBT-BDD to baseline clinical and demographic factors and dropout. RESULTS: Credibility did not differ between the in-person (M=19.3) and digital (M=18.3) trials, p=.24. Expectancy for improvement was moderately higher for in-person (M=58.4) than digital (M=48.3) treatment, p=.005. In the digital trial, no demographic variables were associated with credibility or expectancy. Better BDD-related insight and past non-CBT BDD therapy were associated with greater expectancy. Credibility was associated with lower likelihood of dropout. DISCUSSION: Digital CBT-BDD was regarded as similarly credible to in-person CBT-BDD but with lower expectancy. Tailored expectancy-enhancing strategies could strengthen this novel approach, particularly among those with poorer insight and without prior BDD treatment.

MacroH2A impedes metastatic growth by enforcing a discrete dormancy program in disseminated cancer cells.

MacroH2A variants have been linked to inhibition of metastasis through incompletely understood mechanisms. Here, we reveal that solitary dormant disseminated cancer cells (DCCs) display increased levels of macroH2A variants in head and neck squamous cell carcinoma PDX in vivo models and patient samples compared to proliferating primary or metastatic lesions. We demonstrate that dormancy-inducing transforming growth factor-ß2 and p38α/ß pathways up-regulate macroH2A expression and that macroH2A variant overexpression is sufficient to induce DCC dormancy and suppress metastasis in vivo. Notably, inducible expression of the macroH2A2 variant in vivo suppresses metastasis via a reversible growth arrest of DCCs. This state does not require the dormancy-regulating transcription factors DEC2 and NR2F1; instead, transcriptomic analysis reveals that macroH2A2 overexpression inhibits cell cycle and oncogenic signaling programs, while up-regulating dormancy and senescence-associated inflammatory cytokines. We conclude that the macroH2A2-enforced dormant phenotype results from tapping into transcriptional programs of both quiescence and senescence to limit metastatic outgrowth.

A local tumor microenvironment acquired super-enhancer induces an oncogenic driver in colorectal carcinoma.

Tumors exhibit enhancer reprogramming compared to normal tissue. The etiology is largely attributed to cell-intrinsic genomic alterations. Here, using freshly resected primary CRC tumors and patient-matched adjacent normal colon, we find divergent epigenetic landscapes between CRC tumors and cell lines. Intriguingly, this phenomenon extends to highly recurrent aberrant super-enhancers gained in CRC over normal. We find one such super-enhancer activated in epithelial cancer cells due to surrounding inflammation in the tumor microenvironment. We restore this super-enhancer and its expressed gene, PDZK1IP1, following treatment with cytokines or xenotransplantation into nude mice, thus demonstrating cell-extrinsic etiology. We demonstrate mechanistically that PDZK1IP1 enhances the reductive capacity CRC cancer cells via the pentose phosphate pathway. We show this activation enables efficient growth under oxidative conditions, challenging the previous notion that PDZK1IP1 acts as a tumor suppressor in CRC. Collectively, these observations highlight the significance of epigenomic profiling on primary specimens.

The Role of Social Reactions to Disclosures in the Relationship Between Sexual Assault Acknowledgment and Psychological Symptoms.

Following a sexual assault, women experience a host of negative psychological consequences. While some survivors label their sexual assault experience as such (i.e., are acknowledged survivors), other survivors do not. The effect of acknowledgment of sexual assault on postassault outcomes has yielded mixed findings. It was hypothesized that social reactions may account for the relationship between acknowledgment status and psychological symptoms. Results indicated that acknowledged survivors reported more severe posttraumatic stress disorder symptoms, which were partially accounted for by turning against social reactions. Future studies should explore the mechanisms responsible for these relationships and analyze the individual social reactions.