Mobile Mindfulness Meditation for Cancer-Related Anxiety and Neuropathy: Protocol for a Randomized Controlled Trial.

BACKGROUND: Anxiety- and cancer-related neuropathy are two persistent effects related to treatment for cancer. Mindfulness meditation has been used with substantial impact as a nonpharmacologic intervention to mitigate side and late effects of treatment. Mobile apps are ubiquitous for most of the general population, yet have a particular relevance for cancer survivors, given that physical and geographic limitations can be present. OBJECTIVE: This study aims to describe an ongoing trial of the Mindfulness Coach mobile app for cancer survivors. METHODS: In this randomized waitlist controlled trial, cancer survivors experiencing anxiety- or cancer-related neuropathy (200 for neuropathy and 200 for anxiety) and who had finished primary cancer treatment were invited to participate. Data were collected at 3 time points regardless of randomization condition: baseline, 8 weeks, and 16 weeks. Both face-to-face and web-based recruitment strategies were used. The trial was opened for 2 separate primary outcomes (anxiety- or cancer-related neuropathy). The goal was not to compare these groups but to compare treatment and waitlist groups for each condition. In addition to evaluating the impact of mobile mindfulness on reported anxiety- or cancer-related neuropathy, other pain, fatigue, trauma, sleep, and satisfaction with the Mindfulness Coach app will also be assessed. RESULTS: Outcomes of the study are expected in early 2024. CONCLUSIONS: Mindfulness meditation has become widely practiced, and the use of mobile technology has become ubiquitous. Finding ways to deliver mindfulness meditation to people who have been treated for cancer allows for the intervention to be accessible to a larger number of survivors. The results of this intervention could have implications for further understanding the impact of mindfulness meditation on 2 persistent side and late effects of treatment of cancer, namely anxiety- and cancer-related neuropathy. TRIAL REGISTRATION: ClinicalTrials.gov NCT03581357; https://ClinicalTrials.gov/study/NCT03581357. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/47745.

Virtual Assistants' Response to Queries About Nicotine Replacement Therapy: A Mixed-Method Analysis.

This study focused on investigating the potential of Artificial Intelligent-powered Virtual Assistants (VAs) such as Amazon Alexa, Apple Siri, and Google Assistant as tools to help individuals seeking information about Nicotine Replacement Treatment (NRT) for smoking cessation. The researchers asked 40 NRT-related questions to each of the 3 VAs and evaluated the responses for voice recognition. The study used a cross-sectional mixed-method design with a total sample size of 360 responses. Inter-rater reliability and differences between VAs' responses were examined by SAS software, and qualitative assessments were conducted using NVivo software. Google Assistant achieved 100% voice recognition for NRT-related questions, followed by Apple Siri at 97.5%, and Amazon Alexa at 83.3%. Statistically significant differences were found between the responses of Amazon Alexa relative to both Google Assistant and Apple Siri. Researcher 1's ratings significantly differed from Researcher 2's (p = .001), but not from Researcher 3's (p = .11). Virtual Assistants occasionally struggled to understand the context or nuances of questions, lacked in-depth information in their responses, and provided generic or unrelated responses. Virtual Assistants have the potential to be incorporated into smoking cessation interventions and tobacco control initiatives, contingent upon improving their competencies.

Hula as a physical activity and social support intervention for sustained activity in female breast and gynecologic cancer survivors.

Background: Physical activity improves health and psychosocial functioning for people who have been diagnosed with cancer. Native Hawaiians face disparities for some cancers, including breast cancer. Delivering culturally grounded interventions has the potential to improve enjoyment and adherence to the intervention. We sought to test the adherence and impact of a 6 month randomized wait-list controlled trial of hula. Methods: In this randomized wait-list controlled design people who had been diagnosed with breast or gynecologic cancers were invited to participate with other cancer survivors in a group based setting. Participants were randomized to begin hula immediately or after six months. Attendance was collected and heart-rate measured three times per session. In addition, demographic data, self-report psychosocial data, and biological data (findings will be reported elsewhere) were collected at three time points: baseline, 6 months, and 12 months. The study included six months of hula, twice per week, 60 min each session. In addition, participants committed to practice 60 min per week at home. Results: Participants in the study (n = 42) attended, on average, 72% of the sessions. Significant increase in moderate physical activity (d = 0.50, p = 0.03) was observed in the intervention versus control group. For the measures of intra-individual changes pre-and post-intervention, an increase in total physical activity were seen in the intervention group (d = 0.69, p = 0.003), daily caloric intake decreased (d = -0.62, p = 0.007), and a reduction in waist circumference (d = -0.89, p = 0.0002) that was sustained six months after completion of the intervention. Psychosocially, cognitive functioning significantly declined from baseline to 12 months (d = -0.50, p = 0.03), with role functioning improving (d = 0.55, p = 0.02), social constraints increasing (d = 0.49, p = 0.03), and financial difficulties improving (d = -0.55, p = 0.02). Conclusion: Sustainable physical activity is crucial to improve both the survival and quality of life of cancer survivors. Culturally grounded interventions, such as hula have the potential to increase the maintenance of physical activity. In addition, they create a support group where the benefits of people who have all experienced cancer can gather and garner those benefits of social support, too. This study was registered as a clinical trial through the National Cancer Institute (NCT02351479). Clinical trial registration: Clinicaltrails.gov, NCT02351479.

Preventive and therapeutic opportunities: targeting BAP1 and/or HMGB1 pathways to diminish the burden of mesothelioma.

Mesothelioma is a cancer typically caused by asbestos. Mechanistically, asbestos carcinogenesis has been linked to the asbestos-induced release of HMGB1 from the nucleus to the cytoplasm, where HMGB1 promotes autophagy and cell survival, and to the extracellular space where HMGB1 promotes chronic inflammation and mesothelioma growth. Targeting HMGB1 inhibited asbestos carcinogenesis and the growth of mesothelioma. It is hoped that targeting HMGB1 will be a novel therapeutic strategy that benefits mesothelioma patients. Severe restrictions and/or a complete ban on the use of asbestos were introduced in the 80 and early 90s in the Western world. These measures have proven effective as the incidence of mesothelioma/per 100,000 persons is decreasing in these countries. However, the overall number of mesotheliomas in the Western world has not significantly decreased. There are several reasons for that which are discussed here: (1) the presence of asbestos in old constructions; (2) the development of rural areas containing asbestos or other carcinogenic mineral fibers in the terrain; (3) the discovery of an increasing fraction of mesotheliomas caused by germline genetic mutations of BAP1 and other tumor suppressor genes; (4) mesotheliomas caused by radiation therapy; (5) the overall increase in the population and of the fraction of older people who are much more susceptible to develop all types of cancers, including mesothelioma. In summary, the epidemiology of mesothelioma is changing, the ban on asbestos worked, there are opportunities to help mesothelioma patients especially those who develop in a background of germline mutations and there is the opportunity to prevent a mesothelioma epidemic in the developing world, where the use of asbestos is increasing exponentially. We hope that restrictive measures similar to those introduced in the Western world will soon be introduced in developing countries to prevent a mesothelioma epidemic.

HMGB1 released by mesothelial cells drives the development of asbestos-induced mesothelioma.

Asbestos is the main cause of malignant mesothelioma. Previous studies have linked asbestos-induced mesothelioma to the release of HMGB1 from the nucleus to the cytoplasm, and from the cytoplasm to the extracellular space. In the cytoplasm, HMGB1 induces autophagy impairing asbestos-induced cell death. Extracellularly, HMGB1 stimulates the secretion of TNFα. Jointly, these two cytokines kick-start a chronic inflammatory process that over time promotes mesothelioma development. Whether the main source of extracellular HMGB1 were the mesothelial cells, the inflammatory cells, or both was unsolved. This information is critical to identify the targets and design preventive/therapeutic strategies to interfere with asbestos-induced mesothelioma. To address this issue, we developed the conditional mesothelial HMGB1-knockout (Hmgb1ΔpMeso) and the conditional myelomonocytic-lineage HMGB1-knockout (Hmgb1ΔMylc) mouse models. We establish here that HMGB1 is mainly produced and released by the mesothelial cells during the early phases of inflammation following asbestos exposure. The release of HMGB1 from mesothelial cells leads to atypical mesothelial hyperplasia, and in some animals, this evolves over the years into mesothelioma. We found that Hmgb1ΔpMeso, whose mesothelial cells cannot produce HMGB1, show a greatly reduced inflammatory response to asbestos, and their mesothelial cells express and secrete significantly reduced levels of TNFα. Moreover, the tissue microenvironment in areas of asbestos deposits displays an increased fraction of M1-polarized macrophages compared to M2 macrophages. Supporting the biological significance of these findings, Hmgb1ΔpMeso mice showed a delayed and reduced incidence of mesothelioma and an increased mesothelioma-specific survival. Altogether, our study provides a biological explanation for HMGB1 as a driver of asbestos-induced mesothelioma.

Ethnic differences in respiratory disease for Native Hawaiians and Pacific Islanders: Analysis of mediation processes in two community samples.

OBJECTIVE: The prevalence of asthma and chronic obstructive pulmonary disorder (COPD) is elevated for Native Hawaiians but the basis for this differential is not well understood. We analyze data on asthma and COPD in two samples including Native Hawaiians Pacific Islanders, and Filipinos to determine how ethnicity is related to respiratory disease outcomes. METHODS: We analyzed the 2016 and 2018 Behavioral Risk Factor Surveillance Survey (BRFSS), a telephone survey of participants ages 18 and over in the State of Hawaii. Criterion variables were a diagnosis of asthma or COPD by a health professional. Structural equation modeling tested how five hypothesized risk factors (cigarette smoking, e-cigarette use, second-hand smoke exposure, obesity, and financial stress) mediated the ethnic differential in the likelihood of disease. Age, sex, and education were included as covariates. RESULTS: Structural modeling with 2016 data showed that Native Hawaiian ethnicity was related to higher levels of the five risk factors and each risk factor was related to a higher likelihood of respiratory disease. Indirect effects were statistically significant in almost all cases, with direct effects to asthma and COPD also observed. Mediation effects through comparable pathways were also noted for Pacific Islanders and Filipinos. These findings were replicated with data from the 2018 survey. CONCLUSIONS: Native Hawaiian and Pacific Islander ethnicity is associated with greater exposure to five risk factors and this accounts in part for the ethnic differential in respiratory disease outcomes. The results support a social-ecological model of health disparities in this population. Implications of the findings for preventive interventions are discussed.

Associations for subgroups of E-cigarette, cigarette, and cannabis use with asthma in a population sample of California adolescents.

Knowledge about the respiratory health consequences of adolescents' use of tobacco products with cannabis remains limited. We studied whether e-cigarettes, combustible cigarettes, and cannabis were independently associated with asthma in a population-based sample of 150,634 public high school students (10th and 12th graders), drawn in a two-stage design to be representative of the state of California in 2019-2020. Measures were obtained for use of e-cigarettes, combustible cigarettes, and cannabis; motives for use (three substances); method of use (for cannabis); ever being diagnosed with asthma; and having an asthma attack in past 12 months. Cross-classification indicated Nonuse for 64% of the sample; 15% Dual E-cigarette/Cannabis Use; 10% Exclusive Cannabis Use; 5% Exclusive E-cigarette Use; and 5% Triple Use. Multinomial logistic regression with a three-level criterion variable, controlling for age, sex, parental education, race/ethnicity, and three types of household use showed that compared with Nonuse, odds of Lifetime Asthma (vs. Never Had) was elevated for Triple Use (AOR = 1.14, CI 1.06-1.24), Dual E-cigarette/Cannabis Use (1.17, 1.12-1.23), Exclusive Cannabis Use (1.17, 1.11-1.23), and Exclusive E-cigarette Use (1.10, 1.02-1.18). Similar results were noted for Recent Asthma. Among persons who had used cannabis, 88% of the Triple group and 74% of the Dual E-cigarette/Cannabis group reported both smoking and vaping cannabis. Thus, co-occurrence of e-cigarette and cannabis use was a common pattern among adolescents in this study, and subgroups of cannabis and e-cigarette use showed similar associations with asthma. Preventive approaches should highlight the health implications of exclusive or combined e-cigarette and cannabis use.

Association of SNPs in the PAI1 Gene with Disease Recurrence and Clinical Outcome in Bladder Cancer.

PURPOSE: Bladder cancer (BCa) is one of the most common cancer types worldwide and is characterized by a high rate of recurrence. In previous studies, we and others have described the functional influence of plasminogen activator inhibitor-1 (PAI1) in bladder cancer development. While polymorphisms in PAI1 have been associated with increased risk and worsened prognosis in some cancers, the mutational status of PAI1 in human bladder tumors has not been well defined. METHODS: In this study, we evaluated the mutational status of PAI1 in a series of independent cohorts, comprised of a total of 660 subjects. RESULTS: Sequencing analyses identified two clinically relevant 3' untranslated region (UTR) single nucleotide polymorphisms (SNPs) in PAI1 (rs7242; rs1050813). Somatic SNP rs7242 was present in human BCa cohorts (overall incidence of 72%; 62% in Caucasians and 72% in Asians). In contrast, the overall incidence of germline SNP rs1050813 was 18% (39% in Caucasians and 6% in Asians). Furthermore, Caucasian patients with at least one of the described SNPs had worse recurrence-free survival and overall survival (p = 0.03 and p = 0.03, respectively). In vitro functional studies demonstrated that SNP rs7242 increased the anti-apoptotic effect of PAI1, and SNP rs1050813 was related to a loss of contact inhibition associated with cellular proliferation when compared to wild type. CONCLUSION: Further investigation of the prevalence and potential downstream influence of these SNPs in bladder cancer is warranted.

BAP1 is a novel regulator of HIF-1α.

BAP1 is a powerful tumor suppressor gene characterized by haplo insufficiency. Individuals carrying germline BAP1 mutations often develop mesothelioma, an aggressive malignancy of the serosal layers covering the lungs, pericardium, and abdominal cavity. Intriguingly, mesotheliomas developing in carriers of germline BAP1 mutations are less aggressive, and these patients have significantly improved survival. We investigated the apparent paradox of a tumor suppressor gene that, when mutated, causes less aggressive mesotheliomas. We discovered that mesothelioma biopsies with biallelic BAP1 mutations showed loss of nuclear HIF-1α staining. We demonstrated that during hypoxia, BAP1 binds, deubiquitylates, and stabilizes HIF-1α, the master regulator of the hypoxia response and tumor cell invasion. Moreover, primary cells from individuals carrying germline BAP1 mutations and primary cells in which BAP1 was silenced using siRNA had reduced HIF-1α protein levels in hypoxia. Computational modeling and co-immunoprecipitation experiments revealed that mutations of BAP1 residues I675, F678, I679, and L691 -encompassing the C-terminal domain-nuclear localization signal- to A, abolished the interaction with HIF-1α. We found that BAP1 binds to the N-terminal region of HIF-1α, where HIF-1α binds DNA and dimerizes with HIF-1ß forming the heterodimeric transactivating complex HIF. Our data identify BAP1 as a key positive regulator of HIF-1α in hypoxia. We propose that the significant reduction of HIF-1α activity in mesothelioma cells carrying biallelic BAP1 mutations, accompanied by the significant reduction of HIF-1α activity in hypoxic tissues containing germline BAP1 mutations, contributes to the reduced aggressiveness and improved survival of mesotheliomas developing in carriers of germline BAP1 mutations.

Racial/Ethnic Differences Among Tumor-Infiltrating Lymphocytes in Breast Cancer Tumors.

PURPOSE: Tumor-infiltrating lymphocytes (TILs) have emerged as a predictor of breast cancer treatment response and patient outcomes. Current studies investigating racial/ethnic differences in TILs and immune profiles in breast cancer offer varying results. Our study provides some preliminary data in the breast cancer tumor microenvironment where there is a paucity of information, from Asian and Native Hawaiian/Pacific Islander (NHPI) racial/ethnic groups, not well represented in the literature. METHODS: We reviewed 183 cases of women diagnosed with early stage breast cancer who received neoadjuvant treatment at 2 large health systems in Hawaii between 2008 and 2020. We evaluated clinical and demographic information including: age at diagnosis, self-reported race/ethnicity, tumor stage, tumor subtype according to ER, PR, and HER2 receptor status, the amount of TILs and pathologic complete response (pCR). RESULTS: We found a significantly greater amount of TILs in Asians (37.7%, P = .01) and NHPI (37.2%, P = .02) patients compared to White patients on multivariate analysis. We found no significant differences in pCR among the different racial/ethnic groups. CONCLUSIONS: Racial/ethnic differences in the amount of TILs in breast cancer tumors may suggest differences in the breast tumor microenvironment. This may in part contribute to known outcome disparities in these populations and should be further evaluated.

Genomic Landscape of Circulating-Tumor DNA in a Diverse Cohort of Metastatic Breast Cancer Patients.

INTRODUCTION: Breast cancer is the most prevalent cancer and the second leading cause of cancer death among women in the United States. Liquid biopsy is becoming a more commonly accepted method in clinical practice. Thus, there is a need to investigate ways to utilize circulating-tumor DNA (ctDNA) in metastatic breast cancer (mBC). The primary objective of this study was to characterize the genomic landscape of ctDNA in a diverse patient population and across different subtypes of mBC. METHODS: We analyzed the ctDNA profile in patients (n = 45) with mBC who received a Guardant360 liquid biopsy test. Patient demographics, age at diagnosis, race, subtype, and mutations were included in the analysis. RESULTS: The majority of patients (n = 39, 86.7%) had at least one gene alteration detected in their liquid biopsy. We found no statistically significant differences in genomic landscape according to race. However, there were differences seen in tumor genomics according to age and subtype. Postmenopausal patients were more likely to have detectable disease on liquid biopsy compared to premenopausal patients (p = 0.001). Mutations in ESR1 (n = 10) and PIK3CA (n = 8) were more commonly seen in hormone positive (HR+) mBC, where known tailored treatment options are available (i.e., fulvestrant and alpelisib respectively). The most common alterations detected include TP53 (n = 22) followed by PIK3CA (n = 15), ESR1 (n = 11), CCND1 (n = 7), and ERBB2 (n = 7). CONCLUSION: Liquid biopsies are effective tools that can reveal clinically relevant information including mutational status and therapeutic options.

Racial Disparities in Patient-Provider Communication During Telehealth Visits Versus Face-to-face Visits Among Asian and Native Hawaiian and Other Pacific Islander Patients With Cancer: Cross-sectional Analysis.

BACKGROUND: Telehealth visits increase patients' access to care and are often rated as "just as good" as face-to-face visits by oncology patients. Telehealth visits have become increasingly more common in the care of patients with cancer since the advent of the COVID-19 pandemic. Asians and Pacific Islanders are two of the fastest growing racial groups in the United States, but there are few studies assessing patient satisfaction with telemedicine among these two racial groups. OBJECTIVE: Our objective was to compare satisfaction with communication during telehealth visits versus face-to-face visits among oncology patients, with a specific focus on Asian patients and Native Hawaiian and other Pacific Islander (NHOPI) patients. METHODS: We surveyed a racially diverse group of patients who were treated at community cancer centers in Hawaii and had recently experienced a face-to-face visit or telehealth visit. Questions for assessing satisfaction with patient-physician communication were adapted from a previously published study of cancer survivors. Variables that impact communication, including age, sex, household income, education level, and cancer type and stage, were captured. Multivariable logistic models for patient satisfaction were created, with adjustments for sociodemographic factors. RESULTS: Participants who attended a face-to-face visit reported higher levels of satisfaction in all communication measures than those reported by participants who underwent a telehealth encounter. The univariate analysis revealed lower levels of satisfaction during telehealth visits among Asian participants and NHOPI participants compared to those among White participants for all measures of communication (eg, when asked to what degree "[y]our physician listened carefully to you"). Asian patients and NHOPI patients were significantly less likely than White patients to strongly agree with the statement (P<.004 and P<.007, respectively). Racial differences in satisfaction with communication persisted in the multivariate analysis even after adjusting for sociodemographic factors. There were no significant racial differences in communication during face-to-face visits. CONCLUSIONS: Asian patients and NHOPI patients were significantly less content with patient-physician communication during telehealth visits when compared to White patients. This difference among racial groups was not seen in face-to-face visits. The observation that telehealth increases racial disparities in health care satisfaction should prompt further exploration.

Validation of the Short-Test of Functional Health Literacy in Adults for the Samoan Population.

BACKGROUND: Health literacy encompasses various levels of communication for an individual, provider, and an organization. Validated and reliable tools have been developed to assess health literacy; however, there is a paucity of tools available to assess health literacy in native languages for indigenous and racial/ethnic minority populations. OBJECTIVE: This article shares the process taken to translate and evaluate validation and reliability of the Short Test of Functional Health Literacy in Adults for use with the Samoan population. METHODS: Respondent-driven sampling was used to collect data from 1,543 adults age 45 years and older in American Samoa. A confirmatory factor analysis using a two-factor model for validation was conducted. KEY RESULTS: The validation results indicated a "good fit" in multiple indices and Cronbach's alpha indicated high internal consistency in both the English and Samoan languages. CONCLUSIONS: Developing culturally validated and reliable health literacy assessment tools is important to help health care professionals decrease health disparities and address inadequate health literacy in all cultures. [HLRP: Health Literacy Research and Practice. 2022;6(4):e247-e256.] Plain Language Summary: The INSPIRE project studied the Short Test of Functional Health Literacy in Adults (STOFHLA) tested on the American Samoan population age 50 years and older. The results would show if the STOFHLA is a valid tool to measure functional health literacy in American Samoa adults.

A Diagnostic Gene Expression Signature for Bladder Cancer Can Stratify Cases into Prescribed Molecular Subtypes and Predict Outcome.

Bladder cancer is a biologically heterogeneous disease with variable clinical presentations, outcomes and responses to therapy. Thus, the clinical utility of single biomarkers for the detection and prediction of biological behavior of bladder cancer is limited. We have previously identified and validated a bladder cancer diagnostic signature composed of 10 biomarkers, which has been incorporated into a multiplex immunoassay bladder cancer test, Oncuria™. In this study, we evaluate whether these 10 biomarkers can assist in the prediction of bladder cancer clinical outcomes. Tumor gene expression and patient survival data from bladder cancer cases from The Cancer Genome Atlas (TCGA) were analyzed. Alignment between the mRNA expression of 10 biomarkers and the TCGA 2017 subtype classification was assessed. Kaplan-Meier analysis of multiple gene expression datasets indicated that high expression of the combined 10 biomarkers correlated with a significant reduction in overall survival. The analysis of three independent, publicly available gene expression datasets confirmed that multiplex prognostic models outperformed single biomarkers. In total, 8 of the 10 biomarkers from the Oncuria™ test were significantly associated with either luminal or basal molecular subtypes, and thus, the test has the potential to assist in the prediction of clinical outcome.

Tests for confounding with cigarette smoking in the association of E-cigarette use with respiratory disorder: 2020 National-Sample Data.

Associations of e-cigarette use with respiratory disorder have been demonstrated but it has been unclear whether these are confounded by current or previous cigarette smoking. We address this question through studying different time frames for e-cigarette use and respiratory disorders in 2020 BRFSS data (N = 214,945). E-cigarette use and combustible cigarette smoking were classified into four categories: Participant never used either (Nonuse); used e-cigarettes/cigarettes but not in the past 30 days (Former Use), used in past 30 days on some days (Nondaily Use), or used past 30 days on all days (Daily Use). Contrasts for e-cigarette status and cigarette status (with nonuse as reference group) were entered with covariates in logistic regression with asthma or COPD as criterion. Stratified analyses of e-cigarette use were also performed for smokers and nonsmokers. In the total sample, results showed independent positive associations with both lifetime and current asthma for Former, Nondaily, and Daily e-cigarette use (mostly p < .0001) and the three cigarette indices. Significant positive associations with COPD were found for the three e-cigarette indices (p < .0001) and all the cigarette indices. Stratified analyses showed significant associations of e-cigarette use with respiratory disorder among nonsmokers as well as among smokers. We conclude that independent associations for former e-cigarette use (controlling for current/former smoking) and significant associations of e-cigarette use with respiratory disorder among nonsmokers indicate these associations are not confounded with cigarette smoking and suggest reverse causation is implausible. Findings for former use are discussed with reference to possible mechanisms including sensitization effects.

PAI-1 is a potential transcriptional silencer that supports bladder cancer cell activity.

The extracellular activity of Plasminogen activator inhibitor-1 (PAI-1) is well described, acting as an inhibitor of tissue plasminogen activator and urokinase-type plasminogen activator, impacting fibrinolysis. Recent studies have revealed a pro-tumorigenic role of PAI-1 in human cancers, via the regulation of angiogenesis and tumor cell survival. In this study, immunohistochemical staining of 939 human bladder cancer specimens showed that PAI-1 expression levels correlated with tumor grade, tumor stage and overall survival. The typical subcellular localization of PAI-1 is cytoplasmic, but in approximately a quarter of the cases, PAI-1 was observed to be localized to both the tumor cell cytoplasm and the nucleus. To investigate the potential function of nuclear PAI-1 in tumor biology we applied chromatin immunoprecipitation (ChIP)-sequencing, gene expression profiling, and rapid immunoprecipitation mass spectrometry to a pair of bladder cancer cell lines. ChIP-sequencing revealed that PAI-1 can bind DNA at distal intergenic regions, suggesting a role as a transcriptional coregulator. The downregulation of PAI-1 in bladder cancer cell lines caused the upregulation of numerous genes, and the integration of ChIP-sequence and RNA-sequence data identified 57 candidate genes subject to PAI-1 regulation. Taken together, the data suggest that nuclear PAI-1 can influence gene expression programs and support malignancy.

Clinical Research Professional Providing Care Coordination Support: A Study of Hawaii Minority/Underserved NCORP Community Site Trial Participants.

PURPOSE: Although effective care coordination (CC) is recognized as a vital component of a patient-centered, high-quality cancer care delivery system, CC experiences of patients who enroll and receive treatment through clinical trials (CTs) are relatively unknown. Using mixed methods, we examined perceptions of CC among patients enrolled onto therapeutic CTs through the Hawaii Minority/Underserved National Cancer Institute Community Oncology Research Program. METHODS: The Care Coordination Instrument, a validated instrument, was used to measure patients' perceptions of CC among CT participants (n = 45) and matched controls (n = 45). Paired t-tests were used to compare overall and three CC domain scores (Communication, Navigation, and Operational) between the groups. Semistructured focus group interviews were conducted virtually with 14 CT participants in 2020/2021. RESULTS: CT participants reported significantly higher total CC scores than non-CT participants (P = .0008). Similar trends were found for Navigation and Operational domain scores (P = .007 and .001, respectively). Twenty-nine percent of CT participants reported receiving high-intensity CC assistance from their clinical research professionals (CRPs). Content analysis of focus group discussions revealed that nearly half of the focus group discussions centered on CRPs (47%), including CC support provided by CRPs (26%). Other key themes included general CT experiences (22%) and CRP involvement as an additional benefit to CT participation (15%). CONCLUSION: Our results show that patients on CTs in this study had a more positive CC experience. This may be attributable in part to CC support provided by CRPs. These findings highlight both the improved experience of treatment for patients participating in a trial and the generally unrecognized yet integral role of CRPs as part of a cancer CT care team.

Clinical Utility of Oncuria™, a Multiplexed Liquid Biopsy for the Non-Invasive Detection of Bladder Cancer-A Pilot Study.

Oncuria™ is a validated quantitative multiplex immunoassay capable of detecting bladder cancer from a voided urine sample. Herein, we sought to determine whether Oncuria™ affects physicians' use of non-invasive and invasive diagnostic tests for microhematuria, gross hematuria, and bladder cancer surveillance. We conducted a survey-based study to assess physician management of nine clinical scenarios involving real-world data from patients with gross hematuria, microhematuria, and bladder cancer on surveillance. We randomly sampled 15 practicing urologists and generated data including 135 patient-by-urologist interactions and 2160 decision points. Urologists recommended a selection of diagnostic tests and procedures before and after Oncuria™ results were provided. We assessed changes in provider use of non-invasive and invasive diagnostic tests after Oncuria™ results were provided. Over 90% of all urologists changed their diagnostic behavior in at least one patient case with the addition of Oncuria™ results. The total number of diagnostic procedures was reduced by 31% following the disclosure of a negative Oncuria™ test and 27% following the disclosure of a positive Oncuria™ test. This is pilot study has the potential to shed light on the analysis of our four large multicenter international studies deploying OncuriaTM. The Oncuria™ urine-based test, a molecular diagnostic capable of ruling out the presence of bladder cancer, reduces both unnecessary invasive and non-invasive diagnostics and has the potential to reduce costs and improve patient outcomes.

Trajectories of e-cigarette advertising exposure, e-cigarette use and cigarette smoking in a sample of young adults from Hawaii.

AIM: To test whether intrapersonal growth in e-cigarette advertising exposure over time is associated with growth in e-cigarette use and/or cigarette smoking. DESIGN: Longitudinal study using four waves of data were collected in 6-month intervals between 2018 and 2020. SETTING AND PARTICIPANTS: Participants were 2327 young adults recruited from colleges in Hawaii, USA. MEASUREMENTS: Data were collected on demographics, e-cigarette advertising exposure measured using the cued- recall method and recent (past 30-day) cigarette and e-cigarette use. FINDINGS: The average trajectory for e-cigarette advertising exposure over time was significant and upward [M slope = 0.18 (0.14-0.22), P < 0.0001]. However, average trajectories for e-cigarette [M slope = -0.08 (-0.18 to 0.02), P = 0.09] and cigarette [M slope = -0.14 (-0.30 to 0.02), P = 0.07] use were not. There were significant differences in individual level trajectories across participants for advertising exposure [σ2 = 0.12 (0.10-0.14), P < 0.0001], e-cigarette use [σ2 = 0.22 (0.14-0.30), and cigarette smoking (σ2 = 0.17 [0.09-0.25], P < 0.0001). Individuals with an increasing rate of advertising exposure showed an increasing rate of e-cigarette use [B = 0.63 (0.36-0.90), P < 0.0001). Neither initial level of, nor rate of change in, advertising exposure was significantly associated with cigarette smoking growth factors (P > 0.05). Higher initial level of e-cigarette use was associated with higher initial level of cigarette smoking [B = 0.89 (0.69-1.09), P < 0.0001] but decreased rate of cigarette smoking over time [B = -0.12 (-0.20 to -0.04) P = 0.003]. Rate of change in e-cigarette use was not associated with the rate of change in cigarette smoking (P > 0.05). CONCLUSIONS: Increased exposure to e-cigarette advertising appears to be associated with increased e-cigarette use but not with increased cigarette smoking. Higher initial level of e-cigarette use appears to be associated with higher initial level of cigarette smoking but may be associated with a decreasing rate of cigarette smoking over time.

The feasibility, acceptability, and preliminary efficacy of an mHealth mindfulness therapy for caregivers of adults with cognitive impairment.

Objectives: To examine the feasibility, acceptability, and preliminary efficacy of Mindfulness Coach, an mHealth Mindfulness Therapy intervention.Methods: We recruited 58 informal caregivers of older adults with cognitive impairment for this pilot feasibility trial. Participants completed measures of caregiver burden, stress, anxiety, and depression at baseline, 2 weeks, 4 weeks, and 8 weeks as well as acceptability and usability data at 8-weeks. The mobile app collected in-app use data including minutes spent using the app and number of unique visits to the app.Results: Users found the app acceptable to use and were satisfied with its design and usability. Over the course of the study period, depression, anxiety, caregiver burden and perceived stress improved. These outcome variables also improved more as caregivers spent more time using the Mindfulness Therapy mHealth intervention.Conclusions: Our results suggest that mHealth mindfulness therapy with caregivers of older adults with cognitive impairment is both feasible and acceptable to users, and that it successfully reduces psychological symptoms. Future work should focus on determining the appropriate doses of the mHealth therapy for particular outcomes and strategies to integrate it into routine care. Mindfulness Therapy delivered in an mHealth format may increase access to psychological treatment for caregivers.