Optimal design of two-dimensional water trading based on risk aversion for sustainable development of Daguhe watershed, China.

Water related problems, including water scarcity and pollution, have become increasingly urgent challenges especially in arid and semiarid regions. Two-dimensional water trading (2DWT) mechanism has been designed to unify the quantity and quality of water for relieving the water crisis. This study aims to develop a risk aversion optimization-two dimensional water trading model (RAO-2DWTM) for planning the regional-scale water resources management system (RWMS). This is the first attempt on planning RWMS through risk aversion optimization within the two-dimensional water trading framework. RAO-2DWTM cannot only support in-depth analysis regarding the effect of decision maker's preferences on system risk in different trading scenarios, but also reflect the interaction between water right trading and effluent trading, as well as disclose the optimal scheme of water resource management under uncertainties. Twenty four scenarios associated with different trading scenarios and robust levels are analyzed. The optimization scheme under the optimal risk control level is determined based on TOPSIS. Results revealed that 2DWT would bring high benefit with reduced risk cost, water deficit and emissions, implying the effectiveness of 2DWT mechanism. The results also disclosed that risk aversion behavior can mitigate water scarcity and pollution, as well as reduce risk cost, but may lead to some losses of system benefit. Consequently, decision makers should make trade-offs between system benefit and risk in identifying desired trading schemes.

Influence Mechanism of the Affordances of Chronic Disease Management Apps on Continuance Intention: Questionnaire Study.

BACKGROUND: Mobile health apps are becoming increasingly popular, and they provide opportunities for effective health management. Existing chronic disease management (CDM) apps cannot meet users' practical and urgent needs, and user adhesion is poor. Few studies, however, have investigated the factors that influence the continuance intention of CDM app users. OBJECTIVE: Starting from the affordances of CDM apps, this study aimed to analyze how such apps can influence continuance intention through the role of health empowerment. METHODS: Adopting a stimulus-organism-response framework, an antecedent model was established for continuance intention from the perspective of perceived affordances, uses and gratifications theory, and health empowerment. Perceived affordances were used as the "stimulus," users' gratifications and health empowerment were used as the "organism," and continuance intention was used as the "response." Data were collected online through a well-known questionnaire survey platform in China, and 323 valid questionnaires were obtained. The theoretical model was tested using structural equation modeling. RESULTS: Perceived connection affordances were found to have significant positive effects on social interactivity gratification (t717=6.201, P<.001) and informativeness gratification (t717=5.068, P<.001). Perceived utilitarian affordances had significant positive effects on informativeness gratification (t717=7.029, P<.001), technology gratification (t717=8.404, P<.001), and function gratification (t717=9.812, P<.001). Perceived hedonic affordances had significant positive effects on function gratification (t717=5.305, P<.001) and enjoyment gratification (t717=13.768, P<.001). Five gratifications (t717=2.767, P=.005; t717=4.632, P<.001; t717=7.608, P<.001; t717=2.496, P=.012; t717=5.088, P<.001) had significant positive effects on health empowerment. Social interactivity gratification, informativeness gratification, and function gratification had significant positive effects on continuance intention. Technology gratification and enjoyment gratification did not have a significant effect on continuance intention. Health empowerment had a significant positive effect on continuance intention. Health empowerment and gratifications play mediating roles in the influence of affordances on continuance intention. CONCLUSIONS: Health empowerment and gratifications of users' needs are effective ways to promote continuance intention. The gratifications of users' needs can realize health empowerment and then inspire continuance intention. Affordances are key antecedents that affect gratifications of users' needs, health empowerment, and continuance intention.

Erratum: KCNN4 induces multiple chemoresistance in breast cancer by regulating BCL2A1.

[This corrects the article on p. 3302 in vol. 10, PMID: 33163271.].

KCNN4 induces multiple chemoresistance in breast cancer by regulating BCL2A1.

Multidrug chemoresistance is a major clinical obstacle in breast cancer treatment. We aimed to elucidate the sensitivity to therapeutics in gemcitabine-resistant breast cancer models. Pooled library screening combined with RNA-seq was conducted to explore the potential targets involved in gemcitabine resistance in breast cancer cells. Cytotoxicity and tumor xenograft assays were used to evaluate the effect of calcium-activated channel subfamily N member 4 (KCNN4) inhibitors on the cellular sensitivity of breast cancer cells to chemotherapeutic drugs both in vitro and in vivo. We found that KCNN4 is an important determinant for the cytotoxicity of gemcitabine. Elevated KCNN4 expression enhanced resistance to chemotherapeutic antimetabolites and promoted cell proliferation. Conversely, silencing KCNN4 or chemical inhibition of KCNN4 by the specific inhibitor TRAM-34 inhibited the chemoresistance and cell proliferation. Mechanistically, KCNN4 upregulated BCL2-related protein A1 (BCL2A1) to suppress apoptosis by activating RAS-MAPK and PI3K-AKT signaling. Moreover, high expression levels of KCNN4 and BCL2A1 were associated with shortened disease-free survival in the cohort studies. Collectively, our findings showed that KCNN4 is a key modulator of progression and drug resistance in breast cancer, indicating that targeting KCNN4 may serve as a promising therapeutic strategy to overcome multidrug chemoresistance in this disease.

Nomogram for predicting preoperative lymph node involvement in patients with invasive micropapillary carcinoma of breast: a SEER population-based study.

BACKGROUND: Invasive micropapillary carcinoma (IMPC) is an unusual and distinct subtype of invasive breast tumor with high propensity for regional lymph node metastases. This study was to identify risk factors accounting for IMPC of the breast and to develop a nomogram to preoperatively predict the probability of lymph node involvement. METHODS: A retrospective review of the clinical and pathology records was performed in patients diagnosed with IMPC between 2003 and 2014 from Surveillance, Epidemiology, and End Results (SEER) database. The cohort was divided into training and validation sets. Training set comprised patients diagnosed between 2003 and 2009, while validation set included patients diagnosed thereafter. A logistic regression model was used to construct the nomogram in the training set and then varified in the validation set. Nomogram performance was quantified with respect to discrimination and calibration using R 3.4.1 software. RESULTS: Overall, 1407 patients diagnosed with IMPC were enrolled, of which 527 in training set and 880 in validation set. Logistic regression analysis indicated larger lesions, younger age at diagnosis, black ethnic and lack of hormone receptor expression were significantly related to regional nodes involvement. The AUC of the nomogram was 0.735 (95% confidential interval (CI) 0.692 to 0.777), demonstrating a good prediction performance. Calibration curve for the nomogram was plotted and the slope was close to 1, which demonstrated excellent calibration of the nomogram. The performance of the nomogram was further validated in the validation set, with AUC of 0.748 (95% CI 0.701 to 0.767). CONCLUSIONS: The striking difference between IMPC and IDC remains the increased lymph node involvement in IMPC and therefore merits aggressive treatment. The nomogram based on the clinicalpathologic parameters was established, which could accurately preoperatively predict regional lymph node status. This nomogram would facilitate evaluating lymph node state preoperatively and thus treatment decision-making of individual patients.

Serum miR-4530 sensitizes breast cancer to neoadjuvant chemotherapy by suppressing RUNX2.

PURPOSE: Neoadjuvant chemotherapy (NAC) plays a pivotal role in the treatment of locally advanced breast cancer (LABC); however, breast cancer is a heterogeneous disease, individual responses to chemotherapy are highly variable. Therefore, the purpose of the current research is to identify biomarkers that can predict the chemotherapeutic response. PATIENTS AND METHODS: We recruited 78 patients with primary breast cancer who underwent taxane- and anthracycline-based NAC; these patients were divided into sensitive and resistant groups according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The microRNA microarray was conducted to explore differentially expressed miRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) further validated the relationship between miR-4530 and chemosensitivity in breast cancer patients. RESULTS: No significant differences were observed between the two groups regarding the clinicopathological characteristics. miR-4530 showed the most potential involving breast cancer chemosensitivity. Mechanically, RUNX2 was identified one of the direct targets of miR-4530 and responsible for breast cancer chemosensitivity. CONCLUSION: Our results revealed that elevated serum miR-4530 levels may sensitize breast cancer to taxane- and anthracycline-based NAC by suppressing RUNX2; therefore, this miRNA has the potential to be a new biomarker for predicting breast cancer chemosensitivity.

Similar outcomes between adenoid cystic carcinoma of the breast and invasive ductal carcinoma: a population-based study from the SEER 18 database.

Adenoid cystic carcinoma of the breast (breast-ACC) is a rare and indolent tumor with a good prognosis despite its triple-negative status. However, we observed different outcomes in the present study. Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, we enrolled a total of 89,937 eligible patients with an estimated 86 breast-ACC cases and 89,851 invasive ductal carcinoma (IDC) patients. In our study, breast-ACC among women presented with a higher proportion of triple-negative breast cancer (TNBC), which was more likely to feature well-differentiated tumors, rare regional lymph node involvement and greater application of breast-conserving surgery (BCS). Kaplan-Meier analysis revealed that patients with breast-ACC and breast-IDC patients had similar breast cancer-specific survival (BCSS) and overall survival (OS). Moreover, using the propensity score matching method, no significant difference in survival was observed in matched pairs of breast-ACC and breast-IDC patients. Additionally, BCSS and OS did not differ significantly between TNBC-ACC and TNBC-IDC after matching patients for age, tumor size, and nodal status. Further subgroup analysis of molecular subtype indicated improved survival in breast-ACC patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/Her2-) tumors compared to IDC patients with HR+/Her2- tumors. However, the survival of ACC-TNBC and IDC-TNBC patients was similar. In conclusion, ACCs have an indolent clinical course and result in similar outcomes compared to IDC. Understanding these clinical characteristics and outcomes will endow doctors with evidence to provide the same intensive treatment for ACC-TNBC as for IDC-TNBC and lead to more individualized and tailored therapies for breast-ACC patients.

The different outcomes between breast-conserving surgery and mastectomy in triple-negative breast cancer: a population-based study from the SEER 18 database.

Breast-conserving surgery (BCS) including radiotherapy (RT) has been demonstrated to provide at least equivalent prognosis to mastectomy in early-stage breast cancer. However, studies on triple-negative breast cancer (TNBC) patients are relatively scarce. The current population-based study aimed to investigate the distinct outcomes between BCS+RT and mastectomy in patients with TNBC. Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, we enrolled 11,514 female TNBC cases diagnosed during the years 2010-2013. Those patients were subdivided into BCS+RT (5,469) and mastectomy groups (6,045), and we conducted a survival comparison between the two groups. The endpoints were breast cancer-specific survival (BCSS) and overall survival (OS). In the overall cohort, patients with BCS+RT exhibited distinctly better breast cancer-specific survival (BCSS) (log-rank, p < 0.001) and overall survival (OS) (log-rank, p < 0.001) than did mastectomy patients. When stratifying the TNBC patients according to age, histology grade, TNM stage, tumor size, and lymph node (LN) status, most patients in the BCS+RT group presented with better survival than did the patients in the mastectomy group, except for the grade I (log-rank, p = 0.830, both BCSS and OS) and stage I (log-rank, BCSS, p = 0.127; OS, p = 0.093) patients. In addition, after adjusting for confounding variables by multivariable Cox proportional hazard analysis, BCS+RT still tended to present with higher BCSS and OS. In conclusion, from our study on SEER data, BCS+RT displayed elevated BCSS and OS in TNBC patients compared to mastectomy, at least equally. Our study provided further evidence for surgeons that BCS with RT is available for TNBC patients.