Reflective Engagement With a Digital Physical Activity Intervention Among People Living With and Beyond Breast Cancer: Mixed Methods Study.

BACKGROUND: People living with and beyond breast cancer can face internal barriers to physical activity (eg, fatigue and pain). Digital interventions that promote psychological acceptance and motivation may help this population navigate these barriers. The degree to which individuals (1) adhere to intervention protocols and (2) reflect on and internalize intervention content may predict intervention efficacy. OBJECTIVE: The objective of this study was to characterize the nature of reflective processes brought about by an 8-week acceptance- and mindfulness-based physical activity intervention for insufficiently active survivors of breast cancer (n=75). Furthermore, we explored the potential utility of a metric of reflective processes for predicting study outcomes. METHODS: Of the intervention's 8 weekly modules, 7 (88%) included an item that asked participants to reflect on what they found to be most useful. Two coders conducted directed content analysis on participants' written responses. They assessed each comment's depth of reflection using an existing framework (ranging from 0 to 4, with 0=simple description and 4=fundamental change with consideration of social and ethical issues). The coders identified themes within the various levels of reflection. We fit multiple linear regression models to evaluate whether participants' (1) intervention adherence (ie, number of modules completed) and (2) the mean level of the depth of reflection predicted study outcomes. RESULTS: Participants were aged on average 57.2 (SD 11.2) years, mostly non-Hispanic White (58/75, 77%), and mostly overweight or obese (54/75, 72%). Of the 407 responses to the item prompting personal reflection, 70 (17.2%) were rated as reflection level 0 (ie, description), 247 (60.7%) were level 1 (ie, reflective description), 74 (18.2%) were level 2 (ie, dialogic reflection), 14 (3.4%) were level 3 (ie, transformative reflection), and 2 (0.5%) were level 4 (ie, critical reflection). Lower levels of reflection were characterized by the acquisition of knowledge or expressing intentions. Higher levels were characterized by personal insight, commentary on behavior change processes, and a change of perspective. Intervention adherence was associated with increases in self-reported weekly bouts of muscle-strengthening exercise (B=0.26, SE 0.12, 95% CI 0.02-0.50) and decreases in sleep disturbance (B=-1.04, SE 0.50, 95% CI -0.06 to -2.02). The mean level of reflection was associated with increases in psychological acceptance (B=3.42, SE 1.70, 95% CI 0.09-6.75) and motivation for physical activity (ie, integrated regulation: B=0.55, SE 0.25, 95% CI 0.06-1.04). CONCLUSIONS: We identified a useful method for understanding the reflective processes that can occur during digital behavior change interventions serving people living with and beyond breast cancer. Intervention adherence and the depth of reflection each predicted changes in study outcomes. Deeper reflection on intervention content was associated with beneficial changes in the determinants of sustained behavior change. More research is needed to investigate the relations among digital behavior change intervention use, psychological processes, and intervention efficacy.

Comparing the performance of 2 human papillomavirus assays for a new use indication: a real-world evidence-based evaluation in the United States.

BACKGROUND: The US Food and Drug Administration supports innovations to facilitate new indications for high-risk human papillomavirus testing. This report describes the retrospective testing of stored specimens and analysis of existing data to efficiently and cost-effectively support a new indication for the Onclarity human papillomavirus assay (Becton, Dickinson and Company, BD Life Sciences - Integrated Diagnostic Solutions, Sparks, MD). The performance of this index test was compared with that of a predicate test, the cobas human papillomavirus assay (Roche Diagnostics, Indianapolis, IN). Both human papillomavirus assays are based on real-time polymerase chain reaction platforms that detect the presence of 14 high-risk human papillomavirus genotypes. The predicate assay reports human papillomavirus types 16 and 18 as individual results and the other 12 human papillomavirus genotypes as 1 pooled result. The index assay reports 9 independent results (human papillomavirus types 16, 18, 31, 33/58, 35/39/68, 45, 51, 52, and 56/59/66). Both the index and predicate assays are approved by the Food and Drug Administration for cervical cancer screening, but at the time that this study was initiated, the index human papillomavirus assay was not approved for use with cervical specimens collected in PreservCyt (Hologic, Inc, San Diego, CA) liquid-based cytology media. OBJECTIVE: The performance of the index human papillomavirus assay was compared with that of the predicate human papillomavirus assay for the detection of cervical intraepithelial neoplasia grades 2 or greater and 3 or greater (≥CIN2 or ≥CIN3) using PreservCyt liquid-based cytology specimens collected from women aged 21 to 65 years. In addition, the ability of the index test's extended genotyping to stratify ≥CIN2 and ≥CIN3 risks, using these specimens, was evaluated. STUDY DESIGN: The New Mexico HPV Pap Registry was used to select an age- and cytology-stratified random sample of 19,879 women undergoing opportunistic cervical screening and follow-up in routine clinical practice across New Mexico. A subset (n = 4820) of PreservCyt specimens was selected from 19,879 women for paired testing by the index and predicate human papillomavirus assays within age and cytology strata and included women with or without cervical biopsy follow-up. Point estimate differences and ratios were calculated for cervical disease detection and positivity rates, respectively, with 95% confidence intervals to determine statistical significance. The cumulative risk of ≥CIN2 or ≥CIN3, with up to 5-year follow-up, was estimated for the index assay using Kaplan-Meier methods. RESULTS: The 5-year cumulative ≥CIN3 detection rates were 5.6% for the index assay and 4.6% for the predicate assay (difference, 1.0%; 95% confidence interval, 0.5%-1.5%). The ≥CIN3 positivity rates within <1 year were 95.3% for the index assay and 94.5% for the predicate assay (ratio, 1.01; 95% confidence interval, 0.98-1.06). The ≥CIN3 cumulative positivity rates for the index and predicate assays were also similar at 5 years. Among cases of ≥CIN3, the positive agreement rates between the index and predicate assays for human papillomavirus types 16 and 18 were 100.0% (95% confidence interval, 95.0%-100.0%) and 90.9% (95% confidence interval, 62.3%-98.4%), respectively. Human papillomavirus type 16 carried the highest ≥CIN2 or ≥CIN3 risk, followed by human papillomavirus types 18/31/33/58/52/45 and human papillomavirus types 35/56/59/51/56/59/66. CONCLUSION: The index and predicate human papillomavirus assays demonstrated equivalent performance, and extended human papillomavirus genotyping, using the index assay, provided effective ≥CIN2 and ≥CIN3 risk stratification, supporting a new indication for use of the index assay with PreservCyt.

Timing of venous thromboemboli in patients with acetabular and pelvic ring fractures.

PURPOSE: To determine the timing of symptomatic venous thromboemboli (VTE) in patients sustaining a pelvic and/or acetabular fracture. Secondly, to evaluate for any factors that may influence this timing. METHODS: A retrospective cohort of 47 patients with acetabular and/or pelvic ring injuries who developed VTEs at a single academic level I trauma center were identified from 2012 to 2018. The chronology of VTE diagnosis in relation to date of injury, initial surgery, final surgery, and date of discharge was evaluated. Patients who developed VTEs were then evaluated based on known risk factors for VTE to determine if any of these affected timing. RESULTS: Symptomatic VTEs were diagnosed in 3.8% of patients with pelvic and/or acetabular fractures. In patients who developed a thromboembolism, diagnosis occurred on average 21.5 (± 19.2), 20.7 (± 19.9), 9.8 (± 23.4), and 4.3 (± 27.6) days after injury, index procedure, final procedure, and date of discharge. 25% of patients developed VTE more than 4 weeks after their initial injury. No known risk factors effected the timing of VTE. CONCLUSION: The 2015 OTA expert panel recommends 4 weeks of anticoagulation for orthopedic trauma patients at high risk of VTE, which may be too short a duration. In our cohort, 25% of VTEs occurred greater than 4 weeks after injury. Additional research is needed to clarify the exact duration of anticoagulation after pelvic and acetabular fractures; however, surgeons may want to consider anticoagulating patients for greater than 4 weeks. LEVEL OF EVIDENCE: Level III-retrospective cohort.

Hexahydroquinoline Derivatives Are Selective Agonists for the Adhesion G Protein-Coupled Receptor ADGRG1/GPR56.

GPR56 is a widely expressed adhesion GPCR (AGPCR) that has pleotropic roles in brain development, platelet function, cancer, and more. Nearly all AGPCRs possess extracellular regions that bind protein ligands and conceal a cryptic tethered peptide agonist. AGPCR reception of mechanical or shear force is thought to release the tethered agonist permitting its binding to the AGPCR orthosteric site for consequent activation of G protein signaling. This multistep mechanism of AGPCR activation is difficult to target, emphasizing the need for tool compounds and potential therapeutics that modulate AGPCRs directly. We expanded our cell-based pilot screen for GPR56 small molecule activators to screen >200,000 compounds and identified two promising agonists: 2-(furan-2-yl)-1-[(4-phenylphenyl)carbonyl]pyrrolidine, or compound 4, and propan-2-yl-4-(2-bromophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate, or compound 36. Both compounds activated GPR56 receptors enginered to have impaired tethered agonists and/or be cleavage deficient. Compound 4 activated a subset of group VIII AGPCRs while compound 36 had exclusive specificity for GPR56 among the GPCRs tested. Compound 36 SAR analysis identified an analog with the isopropyl R group replaced with a cyclopentyl ring and the electrophilic bromine replaced with a CF3 group. Analog 36.40 had 40% increased potency over compound 36 and was 20-fold more potent than synthetic peptidomimetics designed from the GPR56 tethered agonist. The new GPCR56 tool compounds discovered in this screen may be used to further advance understanding of GPR56 function and aid development of AGPCR-targeted therapeutics. SIGNIFICANCE STATEMENT: Adhesion G protein coupled receptors (AGPCRs) are a large, clinically relevant class of GPCRs with no available therapeutics, in part due to their unique mechanism of activation. GPR56 is a widely expressed model AGPCR involved in cancer metastasis, hemostasis, and neuron myelination. In the present study, we identified novel small molecule agonists for GPR56. These molecules are among the most potent identified thus far and may become useful leads in the development of a GPR56-targeted therapeutic.

Healthier Energy Balance Behaviors Most Important for Health-Related Quality of Life in Rural Cancer Survivors in Central Pennsylvania.

BACKGROUND: Rural cancer survivors face a greater number of health disparities, including poorer health-related quality of life (HRQoL), than urban cancer survivors. Engagement in healthy lifestyle behaviors also varies between rural and urban cancer survivors. Lifestyle behaviors can improve HRQoL; however, the combination of behaviors most important for HRQoL in rural survivors is unclear. This study examined clusters of lifestyle behaviors in rural cancer survivors, and differences in HRQoL between behavioral clusters. METHODS: Rural cancer survivors in the United States (N = 219) completed a cross-sectional survey. Lifestyle behaviors were classified into unhealthy/healthy binary categories (inactive/active, longer/shorter sedentary time, excessive/acceptable fat intake, very low/higher fruit and vegetable intake, some/no alcohol consumption, and poor/good sleep quality). Behavioral clusters were identified by latent class analysis. HRQoL differences between behavioral clusters were assessed by ordinary least squares regression. RESULTS: The 2-class model demonstrated the best fit and interpretability. The "mostly unhealthy behaviors" class (38.5% of sample) had higher probabilities of all unhealthy behaviors, except alcohol consumption. The "healthier energy balance" class (61.5% of sample) had higher probabilities of active, shorter sedentary, higher fruit and vegetable consumption, excessive fat intake, some alcohol consumption, and poor sleep categories, and reported better HRQoL. CONCLUSIONS: Healthier energy balance behaviors were particularly relevant for HRQoL in rural cancer survivors. Multiple behavior change interventions to improve HRQoL in rural cancer survivors should focus on supporting energy balance behaviors. Many rural cancer survivors may lead very unhealthy lifestyles, placing them at high risk of adverse outcomes. This subpopulation should be prioritized to help alleviate cancer health disparities.

Post-transplant lymphoproliferative disorder: Update on treatment and novel therapies.

Post-transplant lymphoproliferative disorder (PTLD) is rare and heterogeneous lymphoid proliferations that occur as a result of immunosuppression following solid organ transplant (SOT) and haematopoietic stem cell transplant (HSCT) with the majority being driven by EBV. Although some histologies are similar to lymphoid neoplasms seen in immunocompetent patients, treatment of PTLD may be different due to difference in pathobiology and higher risk of treatment complications. The most common treatment approach in SOT PTLD after failing immunosuppression reduction (RIS) takes into consideration a risk-stratified sequential algorithm with rituximab +/- chemotherapy based on phase 2 studies. In HSCT PTLD, RIS alone and chemotherapy are usually ineffective making rituximab +/- RIS as the gold standard of frontline treatment. In this review, we give an update on the treatment of PTLD beyond RIS. We highlight the most recent studies that attempted to incorporate more aggressive chemotherapy regimens and novel treatments into the traditional risk-stratified sequential approach. We also discuss the role of EBV-cytotoxic T lymphocytes in treatment of EBV-driven PTLD. Other novel agents with potential role in PTLD will be discussed in addition to the challenges that could arise with chimeric antigen receptor T-cell therapy and immune checkpoint inhibitors in this population.

Impact of HPV testing in opportunistic cervical screening: Support for primary HPV screening in the United States.

Human papillomavirus (HPV) testing for cervical screening increases diagnosis of precancer and reduces the incidence of cervical cancer more than cytology alone. However, real-world evidence from diverse practice settings is lacking for the United States (U.S.) to support clinician adoption of primary HPV screening. Using a population-based registry, which captures all cervical cytology (with or without HPV testing) and all cervical biopsies, we conducted a real-world evidence study of screening in women aged 30 to 64 years across the entire state of New Mexico. Negative cytology was used to distinguish cotests from reflex HPV tests. A total of 264 198 cervical screening tests (with exclusions based on clinical history) were recorded as the first screening test between 2014 and 2017. Diagnoses of cervical intraepithelial neoplasia grades 2 or 3 or greater (CIN2+, CIN3+) from 2014 to 2019 were the main outcomes. Of cytology-negative screens, 165 595 (67.1%) were cotests and 4.8% of these led to biopsy within 2 years vs 3.2% in the cytology-only group. Among cytology-negative, HPV tested women, 347 of 398 (87.2%) CIN2+ cases were diagnosed in HPV-positive women, as were 147 of 164 (89.6%) CIN3+ cases. Only 29/921 (3.2%) CIN3+ and 67/1964 (3.4%) CIN2+ cases were diagnosed in HPV-negative, cytology-positive women with biopsies. Under U.S. opportunistic screening, across a diversity of health care delivery practices, and in a population suffering multiple disparities, we show adding HPV testing to cytology substantially increased the yield of CIN2+ and CIN3+. CIN3+ was rarely diagnosed in HPV-negative women with abnormal cytology, supporting U.S. primary HPV-only screening.

Assessing the Suitability of a Virtual 'Pink Warrior' for Older Breast Cancer Survivors during COVID-19: A Pilot Study.

The COVID-19 pandemic impacted the conduct of in-person physical activity (PA) interventions among older survivors of BC, who need such interventions to stay active and prevent functional decline. We tested the feasibility of virtually delivering an exergame-based PA intervention to older BC survivors. We enrolled 20 female BC survivors ≥55 years and randomly assigned them to two groups. The intervention group (Pink Warrior 2) received 12 weekly virtual exergame sessions with behavioral coaching, survivorship navigation support, and a Fitbit for self-monitoring. The control group received 12 weekly phone-based survivorship discussion sessions and wore a Mi Band 3. Feasibility was evaluated by rates of recruitment (≥0.92 participants/center/month), retention (≥80%), and group attendance (≥10 sessions), percentage of completed virtual assessments, and number of technology-related issues and adverse events. Intervention acceptability was measured by participants' ratings on a scale of 1 (strongly disagree) to 5 (strongly agree). The recruitment rate was 1.93. The retention and attendance rates were 90% and 88% (≥10 sessions), respectively. Ninety-six percent completed virtual assessments without an adverse event. Acceptability was high (≥4). The intervention met benchmarks for feasibility. Additional research is needed to further understand the impact of virtually delivered PA interventions on older BC survivors.

Effectiveness of elbasvir/grazoprevir plus ribavirin for hepatitis C virus genotype 1a infection and baseline NS5A resistance.

INTRODUCTION AND OBJECTIVES: In clinical trials, patients with hepatitis C virus (HCV) genotype (GT)1a infection and baseline resistance-associated substitutions (RASs) at amino acid positions 28, 30, 31, or 93 receiving elbasvir/grazoprevir for 12 weeks achieved lower rates of sustained virologic response (SVR) than those without baseline RASs. SVR rates in patients with RASs were improved when elbasvir/grazoprevir treatment duration was extended from 12 to 16 weeks and administered concomitantly with ribavirin. MATERIALS AND METHODS: This was a retrospective, observational analysis using electronic health record abstraction. Patients with HCV GT1a infection and RASs at positions 28, 30, 31, or 93 who were prescribed 16 weeks of elbasvir/grazoprevir and ≥ 1 prescription for ribavirin were included. SVR was defined as HCV RNA below the lower limit of quantification ≥ 70 days after end of treatment. RESULTS: The primary analysis included patients with baseline RASs at positions 30, 31, or 93 (n = 76); a secondary analysis included patients with RASs at positions 28, 30, 31, or 93 (n = 93). SVR was achieved by 77.6% (59/76) of patients in the primary analysis and 80.6% (75/93) of those in the secondary analysis. Of the 18 (19.4%) patients in the secondary cohort who failed to achieve SVR, 8 relapsed (4 with treatment-emergent NS5A substitutions) and 10 did not have viral sequencing to distinguish relapse from reinfection. CONCLUSIONS: This analysis highlights the opportunities in leveraging real-world data to further understand treatment outcomes in smaller, discrete subgroups of patients with HCV infection who cannot be thoroughly evaluated in clinical trials.

Structural basis for recognition of N-formyl peptides as pathogen-associated molecular patterns.

The formyl peptide receptor 1 (FPR1) is primarily responsible for detection of short peptides bearing N-formylated methionine (fMet) that are characteristic of protein synthesis in bacteria and mitochondria. As a result, FPR1 is critical to phagocyte migration and activation in bacterial infection, tissue injury and inflammation. How FPR1 distinguishes between formyl peptides and non-formyl peptides remains elusive. Here we report cryo-EM structures of human FPR1-Gi protein complex bound to S. aureus-derived peptide fMet-Ile-Phe-Leu (fMIFL) and E. coli-derived peptide fMet-Leu-Phe (fMLF). Both structures of FPR1 adopt an active conformation and exhibit a binding pocket containing the R2015.38XXXR2055.42 (RGIIR) motif for formyl group interaction and receptor activation. This motif works together with D1063.33 for hydrogen bond formation with the N-formyl group and with fMet, a model supported by MD simulation and functional assays of mutant receptors with key residues for recognition substituted by alanine. The cryo-EM model of agonist-bound FPR1 provides a structural basis for recognition of bacteria-derived chemotactic peptides with potential applications in developing FPR1-targeting agents.

Novel Immune-Based treatments for Diffuse Large B-Cell Lymphoma: The Post-CAR T Cell Era.

Prognosis for patients with refractory/relapsed (R/R) diffuse large B-cell lymphoma (DLBCL) is poor. Immune-based therapeutic treatments such as CD19 Chimeric Antigen Receptor (CAR) T cell therapies have dramatically changed the treatment landscape for R/R DLBCL leading to durable remissions in ~ 50% of patients. However, there remains an unmet need for developing novel therapies to improve clinical outcomes of patients not responding or relapsing after CAR T cell therapies. Lack of suitable immunotherapeutic targets and disease heterogeneity represent the foremost challenges in this emerging field. In this review, we discuss the recently approved and emerging novel immunotherapies for patients with R/R DLBCL in the post-CAR T era and the cell surface targets currently used.

Cytokine Based Immunotherapy for Cancer and Lymphoma: Biology, Challenges and Future Perspectives.

Cytokines regulate both the innate and adaptive immune responses to cancer. Although antitumor activity has been seen for several cytokines in preclinical models, they have had limited success as single therapeutic agents in clinical trials of cancer immunotherapy. However, the possible combinations of cytokines with other immune therapeutics and the advancement in genetic engineering, synthetic biology and cellular and immune therapy has led to the revival of interest in cytokines as anticancer agents. This article will review several immunostimulatory cytokines with anticancer activity, focusing on the those that have been studied in treatment of lymphoma and highlighting recent advances of potential clinical relevance.

Current and emerging monoclonal antibodies, antibody-drug conjugates, and bispecific antibodies in treatment of lymphoma.

The improvement in outcomes seen with the introduction of rituximab, a CD20 monoclonal antibody in combination with chemotherapy or as a single agent in the treatment of indolent non-Hodgkin lymphomas has paved the way for development of various forms of monoclonal antibodies that act in different ways against non-Hodgkin lymphoma tumor cells. These could directly target a single surface antigen resulting in various ways of tumor cells toxicity and killing. Other forms of monoclonal antibodies include antibody-drug conjugates and bispecific antibodies. The role of therapeutic monoclonal antibodies in the treatment of lymphoma will be reviewed, highlighting their mode of action, clinical efficacy, and side effects.

Epigenetic Aberrations and Targets in Peripheral T-Cell Lymphoma.

Peripheral T cell lymphomas (PTCL) comprise a diverse group of aggressive T-cell and NK-cell lymphomas with many subtypes sharing same treatment algorithms despite having different pathobiology and responses to treatment. The molecular advances made in discovery of genetic mutations that disrupt epigenetic modulation in some subtypes of PTCL such as angioimmunoblastic T cell lymphoma and PTCL-not otherwise specified (NOS) may explain the poor outcomes and unsatisfactory responses to frontline line CHOP and CHOP-like therapy seen in this group of lymphomas. In this article, we address the main genetic mutations such as IDH2, TET2 and DNMT3A seen in PTCL and that disrupt the epigenetic modulation pathways, focusing on acetylation, deacetylation and methylation. Since therapeutic agents that target the disrupted epigenetic modulation pathways in PTCL may change treatment landscape in the near future, we will highlight the ones approved for treatment of refractory and/or relapsed PTCL and also the pivotal regimens being evaluated in clinical trials for treatment of frontline and refractory relapsed disease. We stress the importance of determining whether there is an association between the discussed genetic mutations and responses to the highlighted therapeutic agents such that treatments could be better tailored in patients with this kind of lymphoma with unmet needs.

The tethered peptide activation mechanism of adhesion GPCRs.

Adhesion G-protein-coupled receptors (aGPCRs) are characterized by the presence of auto-proteolysing extracellular regions that are involved in cell-cell and cell-extracellular matrix interactions1. Self cleavage within the aGPCR auto-proteolysis-inducing (GAIN) domain produces two protomers-N-terminal and C-terminal fragments-that remain non-covalently attached after receptors reach the cell surface1. Upon dissociation of the N-terminal fragment, the C-terminus of the GAIN domain acts as a tethered agonist (TA) peptide to activate the seven-transmembrane domain with a mechanism that has been poorly understood2-5. Here we provide cryo-electron microscopy snapshots of two distinct members of the aGPCR family, GPR56 (also known as ADGRG1) and latrophilin 3 (LPHN3 (also known as ADGRL3)). Low-resolution maps of the receptors in their N-terminal fragment-bound state indicate that the GAIN domain projects flexibly towards the extracellular space, keeping the encrypted TA peptide away from the seven-transmembrane domain. High-resolution structures of GPR56 and LPHN3 in their active, G-protein-coupled states, reveal that after dissociation of the extracellular region, the decrypted TA peptides engage the seven-transmembrane domain core with a notable conservation of interactions that also involve extracellular loop 2. TA binding stabilizes breaks in the middle of transmembrane helices 6 and 7 that facilitate aGPCR coupling and activation of heterotrimeric G proteins. Collectively, these results enable us to propose a general model for aGPCR activation.

DNA methylation testing with S5 for triage of high-risk HPV positive women.

Methylation of host and viral genes is promising for triage of women with high-risk human papillomavirus infections (hrHPV). Using a population-based sample of hrHPV positive women with cervical biopsies within 12 months after cervical screening, the clinical value of the S5 methylation classifier (S5), HPV genotyping and cytology were compared as potential triage tests, for outcomes of cervical intraepithelial neoplasia (CIN) grade 3 or greater (CIN3+), CIN2+ and CIN2, and the area under the curve (AUC) calculated. S5 scores increased with histopathology severity (Ptrend < .001). For CIN3+, the AUC was 0.780 suggesting S5 provides good discrimination between

The Acceptability of an Electronically Delivered Acceptance- and Mindfulness-Based Physical Activity Intervention for Survivors of Breast Cancer: One-Group Pretest-Posttest Design.

BACKGROUND: Survivors of breast cancer can face internal barriers to physical activity, such as uncertainty and frustration stemming from physical limitations, decreased physical functioning, fatigue, and pain. Interventions that draw from the principles of Acceptance and Commitment Therapy (ACT) may help survivors of breast cancer overcome some of the internal barriers associated with physical activity. OBJECTIVE: The primary aim of this study was to investigate the acceptability of an electronically delivered physical activity intervention for survivors of breast cancer, centered on ACT processes. METHODS: This study used a 1-group pretest-posttest design. We recruited 80 insufficiently active female survivors of breast cancer using a web-based recruitment strategy. The 8-week intervention consisted of weekly modules that featured didactic lessons and experiential exercises targeting key ACT processes in the context of physical activity promotion (namely, values, committed action, acceptance, defusion, and contacting the present moment). We determined intervention acceptability according to study retention (≥70%), adherence rates (≥75% of the participants completing ≥50% of the modules), and posttest survey scores reflecting the perceived ease of use, perceived usefulness, and interest and enjoyment of the intervention (≥5 on a 7-point Likert-type scale). We also evaluated changes in self-reported aerobic and muscle strengthening-physical activity, physical activity acceptance, physical activity regulation, and health-related outcomes. RESULTS: The retention rate (61/80, 76%), adherence rate (60/80, 75%), average perceived ease of use (6.17, SD 1.17), perceived usefulness (5.59, SD 1.40), and interest and enjoyment scores (5.43, SD 1.40) met the acceptability criteria. Participants increased their self-reported aerobic physical activity (Cohen d=1.04), muscle strengthening-physical activity (Cohen d=1.02), physical activity acceptance (cognitive acceptance: Cohen d=0.35; behavioral commitment: Cohen d=0.51), physical activity regulation (identified regulation: Cohen d=0.37; integrated regulation: Cohen d=0.66), increased their ability to participate in social roles and activities (Cohen d=0.18), and reported less fatigue (Cohen d=0.33) and sleep disturbance (Cohen d=0.53). CONCLUSIONS: Electronically delivered acceptance- and mindfulness-based interventions may be useful for promoting physical activity in survivors of breast cancer. Further research is needed to refine these approaches and evaluate their effectiveness.

Plasticity in ligand recognition at somatostatin receptors.

Somatostatin is a signaling peptide that plays a pivotal role in physiologic processes relating to metabolism and growth through its actions at somatostatin receptors (SSTRs). Members of the SSTR subfamily, particularly SSTR2, are key drug targets for neuroendocrine neoplasms, with synthetic peptide agonists currently in clinical use. Here, we show the cryogenic-electron microscopy structures of active-state SSTR2 in complex with heterotrimeric Gi3 and either the endogenous ligand SST14 or the FDA-approved drug octreotide. Complemented by biochemical assays and molecular dynamics simulations, these structures reveal key details of ligand recognition and receptor activation at SSTRs. We find that SSTR ligand recognition is highly diverse, as demonstrated by ligand-induced conformational changes in ECL2 and substantial sequence divergence across subtypes in extracellular regions. Despite this complexity, we rationalize several known sources of SSTR subtype selectivity and identify an additional interaction for specific binding. These results provide valuable insights for structure-based drug discovery at SSTRs.

Feasibility and Effectiveness of a Worksite-Weight-Loss Program for Cancer Prevention among School-District Employees with Overweight and Obesity.

The effects of Vibrant Lives, a 6-month worksite-weight-loss program, were examined in a cohort of school-district employees with overweight or obesity. The VL Basic (VLB) participants received materials and tailored text messages, the VL Plus (VLP) participants additionally received WIFI-enabled activity monitors and scales and participated in health challenges throughout the school year, and the VL Plus with Support (VLP + S) participants additionally received coaching support. The levels of program satisfaction and retention and changes in weight, physical activity (PA), and diet were compared across groups using Pearson chi-square tests, repeated-measure mixed models, and logistic regression. After the program, the VLB (n = 131), VLP (n = 87), and VLP + S (n = 88) groups had average weight losses of 2.5, 2.5, and 3.4 kg, respectively, and average increases in weekly PA of 40.4, 35.8, and 65.7 min, respectively. The VLP + S participants were more likely than the other participants to have clinically significant weight loss (≥3%; p = 0.026). Compared with the VLB participants, the VLP participants were less likely to meet the recommendations for consuming fast food (p = 0.022) and sugar-sweetened beverages (p = 0.010). The VLP and VLP + S participants reported higher program satisfaction than the VLB participants. The VL program facilitates weight loss among school-district employees with overweight and obesity by increasing their PA and healthy diet.

Acceptance- and mindfulness-based techniques for physical activity promotion in breast cancer survivors: a qualitative study.

PURPOSE: The purpose of this study was to develop and characterize the relevance and potential utility of an electronically delivered acceptance- and mindfulness-based approaches to physical activity promotion for insufficiently active breast cancer survivors. METHODS: The acceptance- and mindfulness-based physical activity intervention was delivered to participants electronically over the course of 4-8 weeks. It consisted of didactic videos, experiential exercises, and workbook-type activities that targeted principles from acceptance and commitment therapy (ACT). We conducted semi-structured, in-depth interviews with participants after they completed the intervention. Three coders conducted qualitative data analysis on interview transcripts to identify overarching themes and subthemes. RESULTS: We recruited 30 participants. Of those, 16 engaged in an individual interview. The mean age of the sample was 58.4 years (SD = 13.8). The sample was relatively well educated (50.0% college graduates) and mostly overweight or obese (58.8%). We identified two overarching themes from interviews. They were centered on (1) internal and external barriers to physical activity adherence and (2) the utility of targeting core ACT processes (acceptance and defusion, mindfulness, and values clarification) for physical activity promotion. CONCLUSION: Intervention content was perceived to be acceptable, relevant, and to fulfill important needs related to healthy living. Findings suggest that this approach to physical activity promotion can be delivered effectively online. Electronically delivered acceptance- and mindfulness-based approaches hold promise for helping insufficiently active breast cancer survivors increase physical activity.