Benchmarking and monitoring of urban design and transport features is crucial to achieving local and international health and sustainability goals. However, most urban indicator frameworks use coarse ...spatial scales that either only allow between-city comparisons, or require expensive, technical, local spatial analyses for within-city comparisons. This study developed a reusable, open-source urban indicator computational framework using open data to enable consistent local and global comparative analyses. We show this framework by calculating spatial indicators—for 25 diverse cities in 19 countries—of urban design and transport features that support health and sustainability. We link these indicators to cities’ policy contexts, and identify populations living above and below critical thresholds for physical activity through walking. Efforts to broaden participation in crowdsourcing data and to calculate globally consistent indicators are essential for planning evidence-informed urban interventions, monitoring policy effects, and learning lessons from peer cities to achieve health, equity, and sustainability goals.
Basal-like breast cancers (BLBCs) are a leading cause of cancer death due to their capacity to metastasize and lack of effective therapies. More than half of BLBCs have a dysfunctional BRCA1. ...Although most BRCA1-deficient cancers respond to DNA-damaging agents, resistance and tumor recurrence remain a challenge to survival outcomes for BLBC patients. Additional therapies targeting the pathways aberrantly activated by BRCA1 deficiency are urgently needed.
Most BRCA1-deficient BLBCs carry a dysfunctional INK4-RB pathway. Thus, we created genetically engineered mice with Brca1 loss and deletion of p16
, or separately p18
, to model the deficient INK4-RB signaling in human BLBC. By using these mutant mice and human BRCA1-deficient and proficient breast cancer tissues and cells, we tested if there exists a druggable target in BRCA1-deficient breast cancers.
Heterozygous germline or epithelium-specific deletion of Brca1 in p18
- or p16
-deficient mice activated Pdgfrβ signaling, induced epithelial-to-mesenchymal transition, and led to BLBCs. Confirming this role, targeted deletion of Pdgfrβ in Brca1-deficient tumor cells promoted cell death, induced mesenchymal-to-epithelial transition, and suppressed tumorigenesis. Importantly, we also found that pharmaceutical inhibition of Pdgfrβ and its downstream target Pkcα suppressed Brca1-deficient tumor initiation and progression and effectively killed BRCA1-deficient cancer cells.
Our work offers the first genetic and biochemical evidence that PDGFRβ-PKCα signaling is repressed by BRCA1, which establishes PDGFRβ-PKCα signaling as a therapeutic target for BRCA1-deficient breast cancers.
Hyperspectral image (HSI) analysis has become one of the most active topics in the field of remote sensing, which could provide powerful assistance for sensing a larger-scale environment. ...Nevertheless, a large number of high-correlation and redundancy bands in HSI data provide a massive challenge for image recognition and classification. Hybrid Rice Optimization (HRO) is a novel meta-heuristic, and its population is approximately divided into three groups with an equal number of individuals according to self-equilibrium and symmetry, which has been successfully applied in band selection. However, there are some limitations of primary HRO with respect to the local search for better solutions and this may result in overlooking a promising solution. Therefore, a modified HRO (MHRO) based on an opposition-based-learning (OBL) strategy and differential evolution (DE) operators is proposed for band selection in this paper. Firstly, OBL is adopted in the initialization phase of MHRO to increase the diversity of the population. Then, the exploitation ability is enhanced by embedding DE operators into the search process at each iteration. Experimental results verify that the proposed method shows superiority in both the classification accuracy and selected number of bands compared to other algorithms involved in the paper.
Prostate cancer remains the most common non-cutaneous malignancy among men in the United States. To discover potential serum-based biomarkers for high-risk prostate cancer, we performed a ...high-multiplex immunoassay utilizing patient-matched pre-operative and post-operative serum samples from ten men with high-grade and high-volume prostate cancer. Our study identified six (CASP8, MSLN, FGFBP1, ICOSLG, TIE2 and S100A4) out of 174 proteins that were significantly decreased after radical prostatectomy. High levels of CASP8 were detected in pre-operative serum samples when compared to post-operative serum samples and serum samples from patients with benign prostate hyperplasia (BPH). By immunohistochemistry, CASP8 protein was expressed at higher levels in prostate cancer tissues compared to non-cancerous and BPH tissues. Likewise, CASP8 mRNA expression was significantly upregulated in prostate cancer when compared to benign prostate tissues in four independent clinical datasets. In addition, mRNA levels of CASP8 were higher in patients with recurrent prostate cancer when compared to patients with non-recurrent prostate cancer and high expression of CASP8 was associated with worse disease-free survival and overall survival in renal cancer. Together, our results suggest that CASP8 may potentially serve as a biomarker for high-risk prostate cancer and possibly renal cancer.
This study assesses the efficacy of the Small Business Innovation Research Program on innovation, employment, and business formation in small and nonmetropolitan counties. The primary goal is to ...further understand rural innovation and growth process through government intervention on small business development. Using panel data and employing fixed-effect models, the results suggest that, compared with large metropolitan counties, the Small Business Innovation Research Program may not be an effective program to generate employment and entrepreneurship opportunities in small and nonmetropolitan regions, but it could be a viable source to improve rural innovation outcome. The geographical effects of the program are heterogeneous across implementation years and award agencies. This study contributes to the innovation policy agenda in small and nonmetropolitan regions, which is an important and emerging topic in the field.
Currently, the quest for bamboo materials with high color fastness, rich colors and environmental friendliness is rapidly rising due to its potential applications in construction, furniture and ...decoration. However, finding an easy-to-operate and environmentally friendly dye for bamboo is a necessary task because of the difficulty in treating the dyeing waste liquid of acid dyes and the complexity of the production process of reactive dyes.Five formulations involving metal polyphenol complexes were employed to straightforwardly produce eco-friendly dyed bamboo and the impact of various formulations on the light aging resistance of the dyed veneers was examined. The results indicated that the light resistance of bamboo veneer dyed with the solution containing only FeSO4·7H2O and tannic acid reached level 4, surpassing the undyed bamboo veneer by three levels. The mechanism of enhanced lightfastness of dyed bamboo veneer was elucidated by XPS analysis. The polyphenol iron complex serves a dual purpose: it absorbs ultraviolet rays and scavenges free radicals within the system. Additionally, it reduced the oxidation of phenolics in the substrate, transforming them into dark-colored quinone structures. This process enhanced the light-aging resistance of the finishing materials. Therefore, this work provides a simple and environmentally friendly method for changing the color of bamboo and provides a new idea for the selection of dyes for bamboo dyeing in actual production.
Under the uncertain statistical framework by Liu <xref ref-type="bibr" rid="ref19">19 , there is still a lack of an effective fitting method for uncertain linear models with Box-Cox transformation of ...response variables. For example, for the transformation parameter <inline-formula> <tex-math notation="LaTeX">\lambda </tex-math></inline-formula>, the uncertain least squares estimation will produce a severely low estimation result. In this paper, we propose uncertain Box-Cox regression analysis by utilizing the uncertainty theory to model the imprecise data and applying a generalized Box-Cox transformation indexed by its parameter to validate classic regression assumptions. We use rescaled least squares to estimate unknown parameters and provide an estimate for noises followed by residual analysis for these uncertain Box-Cox regression models. We also give the forecast values and confidence intervals and use a numerical example to demonstrate our methodology. Our work sets a uniformed framework for Box-Cox transformation on the uncertain regression, and extends such regression from linear to nonlinear cases, taking the Johnson-Schumacher growth model as an example.
Distinguishing indolent from clinically significant localized prostate cancer is a major clinical challenge and influences clinical decision-making between treatment and active surveillance. The ...development of novel predictive biomarkers will help with risk stratification, and clinical decision-making, leading to a decrease in over or under-treatment of patients with prostate cancer. Here, we report that Trop2 is a prognostic tissue biomarker for clinically significant prostate cancer by utilizing the Canary Prostate Cancer Tissue Microarray (CPCTA) cohort composed of over 1100 patients from a multi-institutional study. We demonstrate that elevated Trop2 expression is correlated with worse clinical features including Gleason score, age, and pre-operative PSA levels. More importantly, we demonstrate that elevated Trop2 expression at radical prostatectomy predicts worse overall survival in men undergoing radical prostatectomy. Additionally, we detect shed Trop2 in urine from men with clinically significant prostate cancer. Our study identifies Trop2 as a novel tissue prognostic biomarker and a candidate non-invasive marker for prostate cancer.
This article examines the effects of two types of entrepreneurship - new firm formation versus self-employment - on income inequality within cities in the United States. Regression analysis based on ...metropolitan areas between 2005 and 2015 shows that an increase in new firm formation decreases household income inequality. In contrast, more self-employment increases inequality. These results are consistent across different measures of income inequality and model specifications. This study highlights the need for differentiating entrepreneurship in understanding its role in regional development. It further confirms vibrant start-up activity as a key strength of a regional economy.
Abstract
Background
Primary dysmenorrhea (PD) is a leading cause of dysmenorrhea among adolescent girls. Manual acupuncture may be considered as an effective treatment for PD, but high-quality ...evidence remains limited. This trial aims to evaluate the efficacy and safety of acupuncture for the prevention of PD as compared with sham acupuncture and usual care.
Methods/design
This is a three-arm, randomized, controlled clinical trial in which the patients, assessors, and statisticians will be blinded. A total of 300 acupuncture-naive patients who were diagnosed as PD will be randomly allocated to the verum acupuncture, sham acupuncture, or usual care groups in a 2:2:1 ratio. Patients in the verum acupuncture group will receive manual acupuncture at specific acupuncture points with penetrating needling, while those in the sham acupuncture group will receive non-penetrating needling at non-acupuncture points. They will be given five sessions over a menstrual cycle for 3 menstrual cycles. Patients in the usual care group will receive health education and informed to receive manual acupuncture for free after waiting for 7 menstrual cycles. The primary outcome will be the change from baseline in the Cox Menstrual Symptom Scale Score (CMSS). The secondary outcomes will be the changes in Massachusetts General Hospital Acupuncture Sensation Scale (MASS), visual analog scale (VAS), Short-Form McGill Pain Questionnaire 2 (SF-MPQ-2), Pittsburgh Sleep Quality Index (PSQI), Beck Anxiety Inventory (BAI), Beck Depression Inventory II (BDI- II), Acupuncture Expectancy Scale (AES), 60-item NEO Personality Inventory-Short Form (NEO-FFI), and acute medication intake. The adverse events will be recorded at every visit. The analyses will be performed base on a full analysis set (FAS) and a per-protocol set (PPS).
Discussion
This study may provide high-quality evidence regarding the efficacy and safety of manual acupuncture for PD. In addition, the results of this study will help to identify the efficacy of acupuncture due to the specific effects of acupuncture or placebo effects of acupuncture ritual.
Trial registration
Clinical Trials.gov
NCT02783534
. Registered on 26 May 2016
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