End-to-end deep learning method for predicting hormonal treatment response in women with atypical endometrial hyperplasia or endometrial cancer.

Purpose: Endometrial cancer (EC) is the most common gynecologic malignancy in the United States, and atypical endometrial hyperplasia (AEH) is considered a high-risk precursor to EC. Hormone therapies and hysterectomy are practical treatment options for AEH and early-stage EC. Some patients prefer hormone therapies for reasons such as fertility preservation or being poor surgical candidates. However, accurate prediction of an individual patient's response to hormonal treatment would allow for personalized and potentially improved recommendations for these conditions. This study aims to explore the feasibility of using deep learning models on whole slide images (WSI) of endometrial tissue samples to predict the patient's response to hormonal treatment. Approach: We curated a clinical WSI dataset of 112 patients from two clinical sites. An expert pathologist annotated these images by outlining AEH/EC regions. We developed an end-to-end machine learning model with mixed supervision. The model is based on image patches extracted from pathologist-annotated AEH/EC regions. Either an unsupervised deep learning architecture (Autoencoder or ResNet50), or non-deep learning (radiomics feature extraction) is used to embed the images into a low-dimensional space, followed by fully connected layers for binary prediction, which was trained with binary responder/non-responder labels established by pathologists. We used stratified sampling to partition the dataset into a development set and a test set for internal validation of the performance of our models. Results: The autoencoder model yielded an AUROC of 0.80 with 95% CI [0.63, 0.95] on the independent test set for the task of predicting a patient with AEH/EC as a responder vs non-responder to hormonal treatment. Conclusions: These findings demonstrate the potential of using mixed supervised machine learning models on WSIs for predicting the response to hormonal treatment in AEH/EC patients.

Subtypes of Depressed Youth Admitted for Inpatient Psychiatric Care: A Latent Profile Analysis.

Depressed youth frequently present with comorbid symptoms. Comorbidity is related to a poorer prognosis, including treatment resistance, academic problems, risk of suicide, and overall impairment. Studies examining the latent structure of depression support the notion of multiple presentations of depressed youth; however, it is unclear how these presentations are represented among acutely impaired youth. Participants (n = 457) in this naturalistic study were admitted to a psychiatric inpatient unit (Mean age = 14.33 years, SD = 1.94;76% female;46.6% Black/African-American). Selected subscales from the parent-report Behavior Assessment System for Children, Second Edition, were utilized as indicators in a latent profile analysis. Subgroups were validated based on their relationships with meaningful clinical correlates (e.g., family factors, discharge diagnosis) and further described by their associations with demographic variables. A five-class model provided the best balance of fit and parsimony. Subtypes of depressed youth included Predominantly Depressed (39.1%), Oppositional (28.2%), Severely Disruptive (12.3%), Anxious-Oppositional (11.6%), and Anxious-Withdrawn (8.8%). Comorbid symptoms were present in four of the five classes (60.9% of sample). High levels of externalizing symptoms were a prominent clinical feature associated with three classes (52.1% of the sample). Construct validity of the respective classes was demonstrated by differential association with clinical correlates, family characteristics, and demographics. Findings suggest that depressed youth presenting for acute inpatient psychiatric care displayed varied clinical presentations. The identified latent groups aligned with existing research reflecting comorbidity with anxiety, inattention, and externalizing disorders. Findings underscore the need for an increased clinical appreciation of comorbidity and encourage more targeted and effective prevention and treatment strategies.

TP53 mutation and abnormal p53 expression in endometrial cancer: Associations with race and outcomes.

OBJECTIVE: This multi-center cohort study assessed associations between race, TP53 mutations, p53 expression, and histology to investigate racial survival disparities in endometrial cancer (EC). METHODS: Black and White patients with advanced or recurrent EC with Next Generation Sequencing data in the Endometrial Cancer Molecularly Targeted Therapy Consortium database were identified. Clinicopathologic and treatment variables were summarized by race and compared. Overall survival (OS) and progression-free survival (PFS) among all patients were estimated by the Kaplan-Meier method. Cox proportional hazards models estimated the association between race, TP53 status, p53 expression, histology, and survival outcomes. RESULTS: Black patients were more likely than White patients to have TP53-mutated (N = 727, 71.7% vs 49.7%, p < 0.001) and p53-abnormal (N = 362, 71.1% vs 53.2%, p = 0.003) EC. Patients with TP53-mutated EC had worse PFS (HR 2.73 (95% CI 1.88-3.97)) and OS (HR 2.20 (95% CI 1.77-2.74)) compared to those with TP53-wildtype EC. Patients with p53-abnormal EC had worse PFS (HR 2.01 (95% CI 1.22-3.32)) and OS (HR 1.61 (95% CI 1.18-2.19)) compared to those with p53-wildtype EC. After adjusting for TP53 mutation and p53 expression, race was not associated with survival outcomes. The most frequent TP53 variants were at nucleotide positions R273 (n = 54), R248 (n = 38), and R175 (n = 23), rates of which did not differ by race. CONCLUSIONS: Black patients are more likely to have TP53-mutated and p53-abnormal EC, which are associated with worse survival outcomes than TP53- and p53-wildtype EC. The higher frequency of these subtypes among Black patients may contribute to survival disparities.

Identification of Candidate Biomarker and Drug Targets for Improving Endometrial Cancer Racial Disparities.

Racial disparities in incidence and survival exist for many human cancers. Racial disparities are undoubtedly multifactorial and due in part to differences in socioeconomic factors, access to care, and comorbidities. Within the U.S., fundamental causes of health inequalities, including socio-economic factors, insurance status, access to healthcare and screening and treatment biases, are issues that contribute to cancer disparities. Yet even these epidemiologic differences do not fully account for survival disparities, as for nearly every stage, grade and histologic subtype, survival among Black women is significantly lower than their White counterparts. To address this, we sought to investigate the proteomic profiling molecular features of endometrial cancer in order to detect modifiable and targetable elements of endometrial cancer in different racial groups, which could be essential for treatment planning. The majority of proteins identified to be significantly altered among the racial groups and that can be regulated by existing drugs or investigational agents are enzymes that regulate metabolism and protein synthesis. These drugs have the potential to improve the worse outcomes of endometrial cancer patients based on race.

Exploring profiles of coaches' fidelity to Double Check's Motivational Interviewing-embedded coaching: Outcomes associated with fidelity.

Motivational interviewing (MI) is applied in a variety of clinical and coaching models to promote behavior change, with increasing interest in its potential to optimize school-based implementation fidelity. Yet there has been less consideration of fidelity indicators for MI-embedded coaching and their associations with outcomes. We leveraged exisiting data from 151 teachers across 18 schools, who were part of a larger 39 middle school randomized controlled trial of a teacher coaching model, to explore profiles of fidelity and the associations between fidelity and outcomes. We conducted latent profile analysis (LPA) to examine profiles of four components of fidelity (i.e., adherence, dosage, quality, and teachers' responsiveness). Next, we examined whether observed teacher practices and student behaviors varied across fidelity profiles. Because coaches and independent coders reported adherence, we also examined the reliability of retrospective coach adherence ratings. Results indicated that coaches show promise as a reliable rater of adherence. The LPA indicated that there were two (high and lower) fidelity profiles. Statistically significantly fewer instances of student non-cooperation were observed in classrooms where the teacher was engaged in high fidelity coaching, reflecting a large effect size. Moderate-sized, but non-statistically significant, effects also emerged for teacher opportunities to respond and reactive behavior management. We identify concrete areas to ensure that reliability can be achieved in other contexts. Future directions are also considered regarding fidelity measurement and how to optimize coaching.

Endometrial Cancer Characteristics and Risk of Recurrence.

OBJECTIVES: To describe clinicopathologic characteristics and survival outcomes of endometrial adenocarcinomas stratified by mismatch repair (MMR) status. METHODS: Single-institution, retrospective study of all women with endometrioid adenocarcinomas treated from January 2012 through December 2017. Patients were categorized into one of three groups based on MMR testing: intact MMR expression (MMR+), probable MMR mutation (MMR-), or MLH1 hypermethylation (hMLH1+). Demographics, pathologic characteristics, recurrence rates, and survival differences were analyzed. RESULTS: In total, 316 women were included in the analysis: 235 (74.4%) patients in the MMR+ group, 10 (3.1%) in the MMR- group, and 71 (22.5%) in the hMLH1+ group. Patients with hMLH1+ were significantly older, exhibited higher-grade histology and presence of lymphovascular space invasion, and were more likely to have received adjuvant treatment. The early stage hMLH1+ patients were more likely to recur (15.3% hMLH1+ vs 2.3% MMR+ vs 12.5% MMR-, P < .001). Hypermethylation remained a significant predictor of recurrence in multivariable analysis (odds ratio, 5.09; 95% confidence interval [CI], 1.54-16.86; P = .008). Recurrence-free survival was significantly reduced in early stage hMLH1+ (hazard ratio, 7.40; 95% CI, 2.80-21.62; P < .001). CONCLUSIONS: Women with hMLH1+ endometrial cancer have worse prognostic features and recur more frequently, even in patients traditionally considered low risk for recurrence.

Leveraging Motivational Interviewing to Coach Teachers in the Implementation of Preventive Evidence-Based Practices: A Sequential Analysis of the Motivational Interviewing Process.

Though emerging research supports the effectiveness of school-based coaching models utilizing motivational interviewing (MI), an examination of the specific drivers behind these effects is notably lacking in the prevention field. This study leveraged sequential analysis to examine how teachers' verbalization of change talk (i.e., language in support of change) and sustain talk (i.e., language in support of maintaining the status quo) was influenced by coaches' use of MI-consistent (i.e., collaborative language supportive of change) and MI-inconsistent (e.g., confrontational, directive) language, respectively. We also examined whether teacher and coach factors were related to coach-teacher language dynamics. Data were collected from 87 teachers in 16 elementary and middle schools randomized in a trial to the Double Check preventive intervention (see Bradshaw et al., 2018). Audio-recorded coaching feedback sessions were coded using an adapted version of the Motivational Interviewing Sequential Code for Observing Process Exchanges (MI-SCOPE). Sequential analyses indicated that MI-consistent and change talk were significantly more likely than chance to occur consecutively. Teachers' sustain talk was also more likely to occur sequentially with coach use of MI-consistent language and teacher change talk; the latter suggests teacher ambivalence. Coaches rarely used MI-inconsistent language, and its occurrence was only associated with more MI-inconsistent language. Regression analyses indicated that teacher age, efficacy, burnout, classroom organization, and some design features (i.e., cohort, coach, coach-teacher racial match) were associated with different coach-teacher language dynamics. This novel school-based study illustrates how coaching MI evoked teacher change talk related to use of evidence-based programs.

Family and Maternal Characteristics of Children With Co-Occurring ADHD and Depression.

Objective: This study examined differences between children with ADHD and comorbid depression (n = 26), ADHD only (n = 111), and a community control group (n = 130) on measures of family and maternal characteristics. Method: The present study utilized a large, community sample. Diagnoses required positive endorsements from multiple sources. ANOVAs and chi-square tests were conducted to determine group differences. Results: Compared with children with ADHD alone and community controls, mothers of depressed ADHD children reported decreased family cohesion, limited participation in social/recreational activities, increased maternal depressive symptoms, difficulty coping with parenting roles, and higher rates of bipolar and anxiety disorders. Mothers of children with ADHD (with or without comorbid depression) reported increased conflict, decreased cohesion, and poor maternal coping compared with community controls. Conclusion: Findings are consistent with prior literature suggesting that families of children with ADHD and depression demonstrate both similar and unique characteristics. Clinical implications are discussed.

Parent Distress Following Pediatric Burn Injuries.

Parents commonly report elevated distress following a child's burn injury, yet limited research has identified child or injury characteristics that may explain parent distress. The main goal of the current study is to examine prevalence and predictors of parent distress following children's burn injuries by evaluating distress symptoms in a clinic sample of parents whose children present for evaluation and treatment at a regional burn center. Participants included parents of 407 children who experienced a burn injury. Of this sample, follow-up data at a second time point was obtained for 130 children and their caregivers. Parents completed a measure of distress. Clinical and demographic variables were extracted retrospectively from the medical chart. Clinical and at risk levels of distress were reported by nearly 19% of parents at Time 1. Parent distress at Time 1 was associated with child minority race, fewer days since burn injury, and greater burn size. A propensity score was used to account for potential differences between parents with data at Time 1 only versus those with data at Time 2. Parents with Time 2 data tended to have higher levels of distress at Time 1. Of parents with Time 2 data, 17% continued to report elevated distress, and Time 1 distress was the best predictor of later distress. A proportion of parents report elevated distress following their children's burn injuries. Our results suggest that best practices should include routine screening of parent distress following pediatric burn injuries to guide appropriate interventions.

Latent profile analysis of observed parenting behaviors in a clinic sample.

We examined typologies of parenting practices using latent profile analysis (LPA) in a sample of families with young children who had externalizing behavior disorders. We also examined mother and child characteristics associated with class membership using ratings from multiple informants. The sample included pooled data from five parenting treatment outcome research studies on oppositional defiant disorder (ODD) and/or conduct disorder (CD) conducted throughout the past 20 years. These studies included 21 separate cohorts of children resulting in a total of 514 families. All children met diagnostic criteria for ODD or CD and 78 % were male. Parenting practices were observed by independent raters using the Dyadic Parent-child Interactive Coding System-Revised (DPICS-R). Four summary scores (i.e., total critical statements, total commands, total positive, total supportive) from the DPICS-R were used as class indictors in the LPA. Four classes best characterized the parenting practices of this clinic sample, roughly comprising a quarter of the sample each: Positive Only, Negative Only, Positive/Negative, and Neither Positive/Negative. High observed child negative behaviors, low observed child warmth, high socioeconomic status, and low academic performance distinguished the two classes with high negative behaviors (Negative Only, Positive/Negative) from the other classes. These results provide markers of the most common parenting profiles at entry into treatment programs for behavior disorders in young children. Findings have significant implications for the tailoring parenting interventions and supports to specific family needs.

The role of college students' use of protective behavioral strategies in the relation between binge drinking and alcohol-related problems.

Previous research has examined protective behavioral strategies (PBS), or cognitive-behavioral strategies that may be employed when using alcohol to reduce consumption and related problems, as an important predictor of alcohol use and alcohol-related problems. More recently, studies have explored the mediating and moderating role of PBS on the relationships between key alcohol-related risk factors (i.e., drinking motives, depressive symptoms, binge drinking) and alcohol problems; however, current research examining PBS as a moderator of the relationship between alcohol use and related problems has methodological limitations. The purpose of the present study was to extend previous literature to examine the moderating effect of PBS on the relationship between binge drinking and alcohol-related problems. Data were collected and analyzed from 4,154 students at 13 midwestern universities. Findings indicated that PBS moderated the binge drinking-alcohol problems relationship for each of the four measures of binge drinking. However, effects were strongest when binge drinking was measured dichotomously versus continuously. Implications and future directions are discussed. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

The impact of the Incredible Years parent, child, and teacher training programs on children's co-occurring internalizing symptoms.

The Incredible Years (IY) Series includes separate group interventions to improve parenting interactions, teacher classroom management, and child social-emotional regulation. Although originally developed to treat early onset conduct problems, IY targets many of the proposed mechanisms and risk factors for internalizing distress in early childhood. Prior studies have demonstrated the effects of the IY parent intervention on co-occurring depressive symptoms. We attempted to extend these findings by examining the unique and combined effects of IY interventions on children's co-occurring internalizing symptoms. One-hundred and fifty-nine families with children ages 4- to 8-years-old were randomly assigned to parent training (PT); parent plus teacher training (PT + TT); child training (CT); child plus teacher training (CT + TT); parent, child, plus teacher training (PT + CT + TT); or a waiting list control group. Children who received any of the intervention components were more likely to have lower mother-rated internalizing symptoms at posttreatment compared to children in a wait-list control group. Implications for future research and for designing interventions and prevention strategies for children with internalizing symptoms are discussed. (PsycINFO Database Record