A couple-based dyadic coping intervention for colorectal cancer patient-spousal caregiver dyads: A randomized controlled study.

PURPOSE: To evaluate the clinical effects of a couple-focused dyadic coping intervention in colorectal cancer (CRC) couples. METHODS: The study was a single-blinded randomized controlled study which 226 CRC couples were recruited and randomized to either the intervention (N = 113) or the control (N = 113) group. All couples received usual care while the six-week dyadic coping intervention was provided to the intervened couples in psycho-education and skill training methods through face-to-face combined with telephone formats. Measurement data, including dyadic coping, marital satisfaction, quality of life and psychological well-being were collected at pre- and post-intervention periods. And multilevel model (MLM) was applied to analyze the effects of the intervention and the role tendency. RESULTS: A total of 173 couples completed the program and post-intervention evaluation. The retention rate was 76.5%. Results from MLM showed that the dyadic coping intervention is effective in promoting levels of dyadic coping (P < 0.001), marital satisfaction (P = 0.042), mental health (P = 0.006), and positive psychological well-being (P < 0.001), and alleviating depression (P = 0.015) in CRC couples. For role tendency, the intervention found to be more effective in CRC spousal caregivers' positive psychological well-being compared to the patients (P = 0.037). CONCLUSION: The couple-based dyadic coping intervention is effective in promoting dyadic coping and improving psychological adjustment in CRC couples. More studies were needed to further evaluate the program and its long-term efficacy in the future. In addition, given the positive effects of the intervention, clinical nursing stuffs may consider implementing such intervention in their routine work while caring for CRC couples.

Ex vivo drug testing of patient-derived lung organoids to predict treatment responses for personalized medicine.

Lung cancer is the leading cause of global cancer-related mortality resulting in âˆ¼ 1.8 million deaths annually. Systemic, molecular targeted, and immune therapies have provided significant improvements of survival outcomes for patients. However, drug resistance usually arises and there is an urgent need for novel therapy screening and personalized medicine. 3D patient-derived organoid (PDO) models have emerged as a more effective and efficient alternative for ex vivo drug screening than 2D cell culture and patient-derived xenograft (PDX) models. In this review, we performed an extensive search of lung cancer PDO-based ex vivo drug screening studies. Lung cancer PDOs were successfully established from fresh or bio-banked sections and/or biopsies, pleural effusions and PDX mouse models. PDOs were subject to ex vivo drug screening with chemotherapy, targeted therapy and/or immunotherapy. PDOs consistently recapitulated the genomic alterations and drug sensitivity of primary tumors. Although sample sizes of the previous studies were limited and some technical challenges remain, PDOs showed great promise in the screening of novel therapy drugs. With the technical advances of high throughput, tumor-on-chip, and combined microenvironment, the drug screening process using PDOs will enhance precision care of lung cancer patients.

An integrated intervention programme for couples facing colorectal cancer: A randomized controlled trial.

BACKGROUND: Under the guidance of a preliminary Live with Love Conceptual Framework, a Caring for Couples Coping with Colorectal Cancer (4Cs: CRC) programme was designed specifically for colorectal cancer couples. The objectives of this study included examining the efficacy of the programme for couples adapting to colorectal cancer and comparing the effects of different intervention delivery modes (online, face-to-face and blended) on couple outcomes. METHODS: A four-arm randomized controlled trial was conducted among Chinese colorectal cancer couples. Couples were randomly assigned to an online intervention, a face-to-face intervention, a blended intervention or a control group. Self-efficacy, dyadic coping, communication and dyadic outcomes (physical and mental health, negative and positive emotions and marital satisfaction) were evaluated at baseline and 6 weeks later. Analysis of variance (ANOVA) and repeated measures ANOVA were employed to assess between-group differences and within-group effects in the four groups, respectively. RESULTS: A total of 179 couples completed the 6-week study and post-study assessments. The intervention showed generally medium-to-large effects across multiple measured outcomes, including self-efficacy, dyadic coping, communication, mental health, negative emotions and positive emotions for both patients and spouse caregivers. Additionally, interventions delivered through different modes produced equally significant effects on couple outcomes. CONCLUSIONS: The integrated intervention programme is effective in improving cancer adaptation in colorectal cancer couples. Long-term follow-up and a mix of quantitative and qualitative assessments are crucial for further evaluation of the programme. TRIAL REGISTRATION: Retroactive registration is under review.

Phagocytosis-initiated tumor hybrid cells acquire a c-Myc-mediated quasi-polarization state for immunoevasion and distant dissemination.

While macrophage phagocytosis is an immune defense mechanism against invading cellular organisms, cancer cells expressing the CD47 ligand send forward signals to repel this engulfment. Here we report that the reverse signaling using CD47 as a receptor additionally enhances a pro-survival function of prostate cancer cells under phagocytic attack. Although low CD47-expressing cancer cells still allow phagocytosis, the reverse signaling delays the process, leading to incomplete digestion of the entrapped cells and subsequent tumor hybrid cell (THC) formation. Viable THCs acquire c-Myc from parental cancer cells to upregulate both M1- and M2-like macrophage polarization genes. Consequently, THCs imitating dual macrophage features can confound immunosurveillance, gaining survival advantage in the host. Furthermore, these cells intrinsically express low levels of androgen receptor and its targets, resembling an adenocarcinoma-immune subtype of metastatic castration-resistant prostate cancer. Therefore, phagocytosis-generated THCs may represent a potential target for treating the disease.

AXL-initiated paracrine activation of pSTAT3 enhances mesenchymal and vasculogenic supportive features of tumor-associated macrophages.

Tumor-associated macrophages (TAMs) are integral to the development of complex tumor microenvironments (TMEs) and can execute disparate cellular programs in response to extracellular cues. However, upstream signaling processes underpinning this phenotypic plasticity remain to be elucidated. Here, we report that concordant AXL-STAT3 signaling in TAMs is triggered by lung cancer cells or cancer-associated fibroblasts in the cytokine milieu. This paracrine action drives TAM differentiation toward a tumor-promoting "M2-like" phenotype with upregulation of CD163 and putative mesenchymal markers, contributing to TAM heterogeneity and diverse cellular functions. One of the upregulated markers, CD44, mediated by AXL-IL-11-pSTAT3 signaling cascade, enhances macrophage ability to interact with endothelial cells and facilitate formation of primitive vascular networks. We also found that AXL-STAT3 inhibition can impede the recruitment of TAMs in a xenograft mouse model, thereby suppressing tumor growth. These findings suggest the potential application of AXL-STAT3-related markers to quantitatively assess metastatic potential and inform therapeutic strategies in lung cancer.

EE-Explorer: A Multimodal Artificial Intelligence System for Eye Emergency Triage and Primary Diagnosis.

PURPOSE: To develop a multimodal artificial intelligence (AI) system, EE-Explorer, to triage eye emergencies and assist in primary diagnosis using metadata and ocular images. DESIGN: A diagnostic, cross-sectional, validity and reliability study. METHODS: EE-Explorer consists of 2 models. The triage model was developed from metadata (events, symptoms, and medical history) and ocular surface images via smartphones from 2038 patients presenting to Zhongshan Ophthalmic Center (ZOC) to output 3 classifications: urgent, semiurgent, and nonurgent. The primary diagnostic model was developed from the paired metadata and slitlamp images of 2405 patients from ZOC. Both models were externally tested on 103 participants from 4 other hospitals. A pilot test was conducted in Guangzhou to evaluate the hierarchical referral service pattern assisted by EE-Explorer for unspecialized health care facilities. RESULTS: A high overall accuracy, as indicated by an area under the receiver operating characteristic curve (AUC) of 0.982 (95% CI, 0.966-0.998), was obtained using the triage model, which outperformed the triage nurses (P < .001). In the primary diagnostic model, the diagnostic classification accuracy (CA) and Hamming loss (HL) in the internal testing were 0.808 (95% CI 0.776-0.840) and 0.016 (95% CI 0.006-0.026), respectively. In the external testing, model performance was robust for both triage (average AUC, 0.988, 95% CI 0.967-1.000) and primary diagnosis (CA, 0.718, 95% CI 0.644-0.792; and HL, 0.023, 95% CI 0.000-0.048). In the pilot test in the hierarchical referral settings, EE-explorer demonstrated consistently robust performance and broad participant acceptance. CONCLUSION: The EE-Explorer system showed robust performance in both triage and primary diagnosis for ophthalmic emergency patients. EE-Explorer can provide patients with acute ophthalmic symptoms access to remote self-triage and assist in primary diagnosis in unspecialized health care facilities to achieve rapid and effective treatment strategies.

A couple-based dyadic coping intervention for couples coping with colorectal cancer: A pilot feasibility study.

PURPOSE: Compared to individual coping, dyadic coping has significant impact on cancer adaptation in cancer couples. Few intervention studies have focused on dyadic coping in colorectal cancer couples. The purpose of this study was to test the feasibility, acceptability, and preliminary efficacy of a Systemic Transactional Model-guided, couples-based dyadic coping intervention program for colorectal cancer couples. METHODS: A pre-/post-test single-group pilot study was conducted among Chinese colorectal cancer couples. Couples received six intervention sessions delivered by researchers via face-to-face or telephone. Recruitment and retention rates were calculated to assess program feasibility. Quantitative and qualitative post-intervention program evaluation were evaluated to assess acceptability. Additionally, effect sizes were calculated using Dyadic Coping Inventory, Dyadic Adjustments Scale, Medical Outcomes Study 12-item Short-Form, Benefit-Finding Scale, and Hospital Anxiety and Depression Scale to assess preliminary program efficacy. RESULTS: Of the 31 eligible couples approached, 21 dyads completed the baseline questionnaire, with 16 dyads completing the intervention and post-intervention assessments. Recruitment (67.7%) and retention (76.2%) rates supported the feasibility of the intervention program. Program acceptability was supported by participant satisfaction with the program. The intervention had small-to-medium effect sizes (Cohen's d = 0.19-0.48) in improving dyadic coping and most cancer adaptation outcomes for both patients and their spousal caregivers, validating the preliminary efficacy of the program. CONCLUSIONS: The couples-based dyadic coping intervention is feasible, acceptable, and effective for improving dyadic coping levels and cancer adaptation in colorectal cancer couples. Further examination of this intervention program in a large-scale randomized controlled trial is required.

Evaluation and relationship analysis of pea protein on structure and heat-induced gel performance of myofibrillar protein.

BACKGROUND: Surimi products occupy a large market in the food industry, and the gel performance is an important index to evaluate them. Thus, it is of great significance and practical value to find better food ingredients to regulate the structure and gel performance of surimi products. In this study, we used pea protein (PP) to restructure fish myofibrillar proteins (MPs) to achieve regulation of protein gel performance. RESULTS: PP could enhance MP gel performance in terms of compressive strength, water-holding capacity, and some texture parameters. This may be the result of an increasing ß-sheet content and a decreasing trend in the α-helix content, along with enhancements in hydrophobic interactions, nonspecific associations, and ionic bonds in a mixed PP-MP gel. The compressive strength, texture, and water-holding capacity of MP gel were positively correlated with surface hydrophobicity, active sulfhydryl, turbidity, and ß-sheet of the mixed PP-MP system. CONCLUSION: The findings suggest that PP can regulate the gel performance by remodeling the structure of MP. The regulation and correlation analysis between gel performance, structure, and physicochemical properties were explored and established to provide a theoretical basis for improving the quality of surimi products. This study will broaden the application of PP in the field of food processing and provide theoretical guidance for the manufacture of new surimi products. © 2023 Society of Chemical Industry.

Assessing transfer of aluminum during tea brewing and associated population health risks.

Tea is consumed widely around the world owing to its refreshing taste and potential health benefits. However, drinking tea is considered a major route for dietary aluminum exposure in areas where tea consumption is relatively large. To assess the health risk associated with drinking tea, the contamination level of aluminum was determined in 81 tea samples. The transfer rate of aluminum during tea brewing was investigated. Then based on the site-specific exposure parameters such as consumption data and body weight for six different subpopulations in Fujian, the exposure risks were estimated using a probabilistic approach. Results demonstrate that the contents of aluminum in green tea, white tea, oolong tea, and black tea were significantly different according to the one-way ANOVA analysis (p < 0.05). The transfer rate of aluminum were 32.6%, 31.6%, 26.3%, and 14% for white tea, black tea, oolong tea, and green tea, respectively. With respect to the oral reference dose, the exposure of inhabitants in Fujian to aluminum through drinking tea is under control (even at the 99th percentile).

A qualitative study about colorectal cancer patients and spousal caregivers' experience and needs during COVID-19: implications for self-efficacy intervention.

Objective: This study aims to understand the experiences of colorectal cancer (CRC) patients and their spousal caregivers during the COVID-19 pandemic and to refine a self-efficacy (SE) intervention for these couples. Methods: A descriptive phenomenological approach was used in this study. Data were collected from 11 CRC couples. All interviews were recorded, transcribed, and analyzed using the Colaizzi strategy. Results: Three themes and eight subthemes emerged: (1) Get and contribute support, (2) Life's challenges, and (3) Journey of reconstruction. The CRC couples encountered escalating challenges in coping with cancer during COVID-19. At the same time, they have received considerable support and developed confidence in rebuilding themselves in the process. Healthcare providers are advised to focus on giving appropriate support to CRC couples, so they can go further. Conclusions: This study gave insights into healthcare providers on the experiences of CRC couples and the development of SE intervention program to support these couples: (1) initially providing caregiving training for spousal caregivers and psychological support for patients, (2) encouraging self-care for CRC couples in the middle stage, (3) guiding them to view life positively in the later stage, and (4) assessing their situation in time to identify their needs and to provide support. Healthcare providers are recommended to increase flexibility in the SE intervention program delivery format to reduce the impact of COVID-19 on CRC couples.

The application of eHealth in cancer survivorship care: A review of web-based dyadic interventions for post-treatment cancer survivors and caregivers.

Objective: Both cancer survivors and caregivers often experience a range of problems and unmet needs during the post-treatment survivorship. Web-based dyadic interventions may be critical for cancer survivors and their caregivers. This article aims to systematically explore existing web-based dyadic interventions for post-treatment cancer survivors and caregivers in terms of intervention focus, content, delivery, and outcomes and to provide valuable recommendations for future research. Methods: A comprehensive literature search was conducted to identify articles published in English or Chinese in the English databases PubMed, EMBASE, MEDLINE, PsycINFO, and Cochrane Library, and the Chinese databases CNKI and Wanfang Data, from database inception to March 2022. The literature references were also manually searched for additional eligible articles. Results: Thirteen studies were included for analysis in this review. Cancer couple dyads were the main target of the interventions that were included. Information support, psychotherapy, self-management skills training, dyadic coping, and social support were the main intervention treatment elements. The combined results in this review support the feasibility, usability, and acceptability of eHealth interventions and showed trends in positive intervention effects for cancer survivors and caregivers in terms of self-efficacy, quality of life, physical health, mental health, and dyadic relationship. Conclusions: This review identifies the positive outcomes of web-based dyadic interventions for post-treatment cancer survivors and caregivers. Further development and refinement of post-treatment cancer survivor-caregiver dyadic web-based interventions, with personalized online platforms and multiple components for supportive care needs, should be promoted.

The Sources of Research Self-Efficacy in Postgraduate Nursing Students: A Qualitative Study.

Postgraduate students are required to undertake a series of research assignments. Research self-efficacy is regarded as the sense of faith in their ability to accomplish research tasks. However, it is unclear how research self-efficacy plays a role in second-year nursing postgraduate students who have been enrolled for a period of time and have not yet met graduation requirements. This study aims to explore the sources of second-year nursing postgraduate students' research self-efficacy in response to research tasks. A descriptive phenomenological approach was used in this study. A total of 13 second-year nursing postgraduate students participated in semi-structured interviews using a purposive sampling method. Content analysis was applied to analyze the interview data after verbatim transcription. Participants stated that they had gained a great deal of support but were somewhat less confident. Three themes were refined: (a) intrinsic sources of research self-efficacy (differences in cognitive ability, internal driving force, with successful experience), (b) extrinsic sources of research self-efficacy (family support, peer support, mentor support), and (c) unmet support may cause low self-confidence (inadequate self-support, inadequate extrinsic-support, lack of motivation from successful experiences). The postgraduate students in this study accepted the objectives of the master's training and actively practiced research exploration. They were motivated to persevere through their internal and external support, albeit with some negative aspects that deserve our attention. Interventions for postgraduate students' cognitive awareness, constant support during their postgraduate career, and finally, guiding summaries may have a positive impact on their self-efficacy.

The relationship between axial length/corneal radius of curvature ratio and stress-strain index in myopic eyeballs: Using Corvis ST tonometry.

Purpose: This study aimed to investigate the correlation of axial length/corneal radius of curvature ratio with stress-strain index (SSI). Methods: Retrospective analysis was conducted to compare the right eyes of those with high myopia (HM, n = 132; age and 10-48 years) with those without high myopia (NHM, n = 135; age and 7-48 years), where the baseline axial length, corneal radius of curvature ratio, and central corneal thickness were analyzed; the differences in two groups were compared; and the relationship of axial length and axial length/corneal radius of curvature ratio with SSI were explored. Results: Compared with AL < 26mm, SSI significantly decreased when AL ≥ 26 mm (p = 0.001), while there was no correlation with AL in the NHM group (r = -0.14, p = 0.12) or HM group (r = -0.09, p = 0.32). AL/CR was significantly associated with SSI in both the NHM (r = -0.4, p < 0.001) and HM (r = -0.18, p = 0.04) groups. In the NHM group, AL/CR was significantly associated with SSI (unstandardized beta = -0.514, se = 0.109, p < 0.001) with the adjustment of age and gender. Additionally, a significant association of SSI with AL/CR was also found after adjusting for age and gender (unstandardized beta = -0.258, se = 0.096, and p = 0.0082) in the HM group. Conclusion: SSI showed a significant negative correlation with AL/CR in patients without high myopia and in patients with high myopia. However, SSI exhibited no decrease with the worsening of myopia, but it gradually remained stable at a low level. The findings of this study validate, to some extent, the possibility of analyzing the dynamic changes in ocular wall stiffness during the development of myopia by measuring in vivo corneal biomechanical parameters.

Safety and tolerance assessment of milk fat globule membrane-enriched infant formulas in healthy term Chinese infants: a randomised multicenter controlled trial.

BACKGROUND: Milk fat globule membrane (MFGM), natural to breast milk, is essential for neonatal development, but lacking from standard infant formulas. OBJECTIVES: To evaluate the safety and tolerability of MFGM supplementation in formula for infants 0 to 12 months. METHODS: In a prospective, multicentre, double-blind, randomized trial, healthy term infants were randomized to a standard formula (SF, n = 104) or an MFGM-enriched formula (MF, n = 108) for 6 months and a corresponding follow-on formula until 12 months. Exclusively breast-fed infants (n = 206) were recruited as the reference group (BFR). Tolerance and safety events were recorded continuously. Anthropometric measurements were assessed at enrolment, 42 days and 4, 6, 8 and 12 months. RESULTS: Infants (n = 375) completed the study with average dropout of < 20%. Stool frequency, color, and consistency between SF and MF were not significantly different throughout, except the incidence of loose stools in MF at 6 months being lower than for SF (odds ratio 0.216, P < 0.05) and the frequency of green-colored stools at 12 months being higher in MF (CI 95%, odds ratio 8.92, P < 0.05). The BFR had a higher frequency of golden stools and lower rate of green stools (4-6 months) than the two formula-fed groups (P < 0.05). SF displayed more diarrhoea (4.8%) than MF (1%) and BFR (1%) at the 8-month visit (P < 0.05). BFR (0-1%) had significantly less (P < 0.05) lower respiratory infections than MF (4.6-6.5%) and SF (2.9-5.8%) at 6- and 8-months, respectively. Formula intake, frequency of spit-up/vomiting or poor sleep were similar between SF and MF. Growth rate (g/day) was similar at 4, 6, 8 and 12 months between the 3 groups, but growth rate for BFR was significantly higher than for SF and MF at 42 days (95% CI, P = 0.001). CONCLUSIONS: MFGM-enriched formula was safe and well-tolerated in healthy term infants between 0 and 12 months, and total incidences of adverse events were similar to that for the SF group. A few differences in formula tolerance were observed, however these differences were not in any way related to poor growth.

Prediction and Health Risk Assessment of Copper, Lead, Cadmium, Chromium, and Nickel in Tieguanyin Tea: A Case Study from Fujian, China.

Heavy metal is widespread in food and the environment due to multiple origins, raising concerns over their persistent potential health risks. Contamination of multiple heavy metals in tea leaves is frequently reported. However, the dietary exposure risk that heavy metals in Tieguanyin tea (a famous type of oolong tea,) pose to different subpopulations has not been explored. In this study, contaminations of five heavy metals (Cu, Pb, Cr, Cd, and Ni) of concern in Tieguanyin tea were monitored, then the related health risk was assessed for six different subpopulations based on tea brewing experiments and a previous consumption survey. Results show that the mean levels found were as follows: 8.18 mg/kg (Cu), 0.84 mg/kg (Pb), 0.51 mg/kg (Cr), 0.04 mg/kg (Cd), and 1.90 mg/kg (Ni), respectively, and their transfer rates during tea brewing varied within 10.2-70.4%. All estimated daily intakes of individual targeted elements via Tieguanying tea consumption were far below their corresponding tolerable limits. The adjusted hazard index value ranged from 1.1 × 10-2 to 1.7 × 10-2, indicating that exposure to these five elements via drinking Tieguanyin tea would not pose significant non-cancer risks for six subpopulations under the current consumption habit. In addition, the carcinogenic risks associated with heavy metals (Pb, Cd, and Cr) were acceptable because no total cancer risk values exceeded the 10-4 threshold. However, in order to improve consumer protection, we still suggest that considerable attention should be paid to Pb, Ni, and Cd because of their high concentration in infusion, high extraction rate, and major carcinogenic risk contribution, respectively.

The development and evaluation of a web-based complex intervention: The caring for couples coping with colorectal cancer "4Cs: CRC" program.

Objective: This article aims to systematically present the completed process of developing and evaluating a web-based complex intervention called 'Caring for Couples Coping with Colorectal Cancer "4Cs: CRC" program'; summarize the findings of this integrated supportive program; and provide valuable experience and suggestions for future interventions. Methods: The integrated 4Cs: CRC program was guided by the Medical Research Council (MRC) framework, which has widely been used to develop and evaluate complex interventions. Three stages were completed for the program development, namely: (1) developing a complex intervention; (2) assessing feasibility; and (3) evaluating the complex intervention. Results: Based on a series of interactive studies and a dyadic theoretical framework, the 4Cs: CRC program was developed into an integrated supportive six-week program that includes five weekly web-based interventions, as well as three biweekly face-to-face sessions. In particular, an online platform was designed to provide web-based interventions for couples facing colorectal cancer (CRC). Both the pilot study and qualitative process evaluation showed the program's preliminary feasibility, acceptability, and effectiveness. Conclusions: Under the guidance of the MRC framework, the 4Cs: CRC program was developed based on multiple interacting components. The program was initially proven to be feasible, acceptable, and effective at supporting CRC couples in mainland China, but requires further improvements according to the qualitative process evaluation results. More importantly, a full-scale randomized controlled trial is required to further explore the program's effectiveness in a wider population.

Plasmacytoma variant translocation 1 stabilized by EIF4A3 promoted malignant biological behaviors of lung adenocarcinoma by generating circular RNA LMNB2.

Increasing evidence suggests that plasmacytoma variant translocation 1 (PVT1) plays a vital role in the development of multiple tumors including lung adenocarcinoma (LUAD). Eukaryotic initiation factor 4A-3 (EIF4A3) is considered a key factor in human cancers. However, the role and potential mechanism of PVT1 combined with EIF4A3 in LUAD remain unclear. This study investigated the effects and regulatory mechanisms of PVT1, EIF4A3, and circLMNB2 on the growth, migration, invasion, and epithelial-mesenchymal transition (EMT) of LUAD cells (H1299 and HCC827 cells) The expression level, diagnostic value and prognostic significance of PVT1, EIF4A3, and circLMNB2 were assessed, and enrichment analysis was performed using R package. Rescue experiments and a xenograft model were used to validate the PVT1/EIF4A3/circLMNB2 axis in LUAD. PVT1 and EIF4A3 were upregulated and indicated poor prognosis in LUAD. Knockdown of PVT1 and EIF4A3 suppressed LUAD cell proliferation, migration, invasion, and EMT. Mechanistically, PVT1 was stabilized by EIF4A3. PVT1 could recruit EIF4A3 to promote circLMNB2 expression. Rescue experiments indicated that circLMNB2 overexpression could reverse the reduced behavior caused by PVT1 or EIF4A3 knockdown. Enrichment analysis showed that PVT1/EIF4A3/circLMNB2 may regulate LUAD development by participating in ribosome biogenesis and spliceosome formation. Our findings demonstrate that PVT1/EIF4A3/circLMNB2 enhances the malignant behaviors of LUAD cells, providing a novel perspective for the clinical treatment of LUAD.

2-Hydroxyglutarate destabilizes chromatin regulatory landscape and lineage fidelity to promote cellular heterogeneity.

The epigenome delineates lineage-specific transcriptional programs and restricts cell plasticity to prevent non-physiological cell fate transitions. Although cell diversification fosters tumor evolution and therapy resistance, upstream mechanisms that regulate the stability and plasticity of the cancer epigenome remain elusive. Here we show that 2-hydroxyglutarate (2HG) not only suppresses DNA repair but also mediates the high-plasticity chromatin landscape. A combination of single-cell epigenomics and multi-omics approaches demonstrates that 2HG disarranges otherwise well-preserved stable nucleosome positioning and promotes cell-to-cell variability. 2HG induces loss of motif accessibility to the luminal-defining transcriptional factors FOXA1, FOXP1, and GATA3 and a shift from luminal to basal-like gene expression. Breast tumors with high 2HG exhibit enhanced heterogeneity with undifferentiated epigenomic signatures linked to adverse prognosis. Further, ascorbate-2-phosphate (A2P) eradicates heterogeneity and impairs growth of high 2HG-producing breast cancer cells. These findings suggest 2HG as a key determinant of cancer plasticity and provide a rational strategy to counteract tumor cell evolution.

The Dyadic Effects of Self-Efficacy on Quality of Life in Advanced Cancer Patient and Family Caregiver Dyads: The Mediating Role of Benefit Finding, Anxiety, and Depression.

Objectives: To explore the dyadic interdependence of self-efficacy, benefit finding, anxiety, depression, and QOL in cancer patient (CP) and family caregiver (FC) dyads, and to ascertain the dyadic effects of self-efficacy on quality of life (QOL) in CP-FC dyads. Methods: Conducted from November 2014 to December 2015, participants comprised 772 CP-FC dyads. The study surveyed participant characteristics, self-efficacy, benefit finding, anxiety, depression, and QOL. Data were analyzed using Pearson's correlation, T-test, and actor-partner interdependence mediation model (APIMeM). Results: CPs' self-efficacy was positively correlated with both their own and FCs' benefit finding and mental component summary (MCS), and negatively associated with anxiety and depression (all Ps < 0.01, |r| = 0.144∼0.432). However, CPs' self-efficacy was only positively correlated with their own physical component summary (PCS) (r = 0.193), but not FCs' PCS. The same profile was identified in FCs' self-efficacy (all Ps < 0.01, |r| = 0.100∼0.468). FCs reported higher levels of self-efficacy and PCS compared to CPs (both Ps < 0.001). Significant positive correlations (r = 0.168-0.437) were identified among all paired variables in CP-FC dyads (all Ps < 0.001). To some extent, dyads' self-efficacy influences dyads' MCS and PCS through improving positive emotions (benefit finding) and relieving negative emotions (anxiety and depression). Conclusions: Study findings not only support the dyadic interdependence of self-efficacy, benefit finding, anxiety, depression, and QOL in CP-FC dyads but confirm the hypothesis that dyads' self-efficacy may impact their MCS/PCS via an indirect approach to improve benefit finding and relieve anxiety and/or depression in CP-FC dyads.

Cellular junction and mesenchymal factors delineate an endometriosis-specific response of endometrial stromal cells to the mesothelium.

Endometriosis is a debilitating gynecologic disorder that affects ∼10% of women of reproductive age. Endometriosis is characterized by growth of endometriosis lesions within the abdominal cavity, generally thought to arise from retrograde menstruation of shed endometrial tissue. While the pathophysiology underlying peritoneal endometriosis lesion formation is still unclear, the interaction between invading endometrial tissue and the peritoneal mesothelial lining is an essential step in lesion formation. In this study, we assessed proteomic differences between eutopic endometrial stromal cells (ESCs) from women with and without endometriosis in response to peritoneal mesothelial cell (PMC) exposure, using single-cell cytometry by time-of-flight (CyTOF). Co-cultured primary eutopic ESCs from women with and without endometriosis with an established PMC line were subjected to immunostaining with a panel of Maxpar CyTOF metal-conjugated antibodies (n = 28) targeting cell junction and mesenchymal markers, which are involved in cell-cell adhesions and epithelial-mesenchymal transition. Exposure of the ESCs to PMCs resulted in a drastic shift in cellular expression profiles in ESCs derived from endometriosis, whereas little effect by PMCs was observed in ESCs from non-endometriosis subjects. The transcription factor SNAI1 was consistently repressed by PMC interactions. ESCs from endometriosis patients are unique in that they respond to PMCs by undergoing changes in adhesive properties and mesenchymal characteristics that would facilitate lesion formation.