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This paper introduces an improved weighted nuclear norm with a total variation model tailored for removing multiplicative noise. The model incorporates a weight matrix to regularize the residual matrix, effectively leveraging image redundancy to differentiate various statistical properties of the noise. Since there is no guarantee of a unique solution, the model is reformulated as a linear equality constraint problem and decomposed into two subproblems. These are addressed by using the alternating direction method of multipliers and the split Bregman method, respectively. In addition, each alternative update step has a closed-form and convergent solution. After obtaining the denoised image in the log-domain, the recovered image is given by using the exponential function and bias correction. Experimental evaluations demonstrate the efficacy of our algorithms in enhancing image restoration quality.

Abstract Introduction With locally advanced pancreatic cancer (LAPC), uncontrolled local tumor growth frequently leads to mortality. Advancements in radiotherapy (RT) techniques have enabled conformal delivery of escalated‐dose RT (EDR), which may have potential local control and overall survival (OS) benefits based on retrospective and early prospective studies. With evidence for EDR emerging, we characterized the adoption of EDR across the United States and its associated outcomes. Methods We searched the National Cancer Database for nonsurgically managed LAPC patients diagnosed between 2004 and 2019. Pancreas‐directed RT with biologically effective doses (BED10) ≥39 and ≤70 Gy was labeled conventional‐dose RT (CDR), and BED10 >70 and ≤132 Gy was labeled EDR. We identified associations of EDR and OS using logistic and Cox regressions, respectively. Results Among the definitive therapy subset (n = 54,115) of the entire study cohort (n = 91,493), the most common treatments were chemotherapy alone (69%), chemotherapy and radiation (29%), and RT alone (2%). For the radiation therapy subset (n = 16,978), use of pancreas‐directed RT remained between 13% and 17% over the study period (ptrend > 0.999). Using multivariable logistic regression, treatment at an academic/research facility (adjusted odds ratio [aOR] 1.46, p

Purpose – The purpose of this study is to explore the relationship between gender disparities in rural education attainments and agricultural landownership (ALO) in Sub-Sahara Africa with Sustainable Development Goal (SDG) perspective. Design/methodology/approach – This study uses SDG indicators interactions and pairwise correlation analysis. Findings – There is a significant negative association between gender disparities in rural education attainments and ALO in Sub-Sahara Africa. Such negative relationship is not influenced by national economic development and living standards. Research limitations/implications – The data is limited with 16 Sub-Sahara African countries, and as this is an early output of a number of follow-up studies in the author’s plan, the methodology is relatively simple. Practical implications – Reducing gender disparity in rural Sub-Sahara Africa especially in ALO requires more integrated approaches which also address other aspects of sustainable development. This is particularly the situation because of the strong male-favored customary practices in rural Sub-Sahara Africa. The prioritization of different dimensions of sustainable development is also important in Sub-Sahara Africa. Social implications – Strong awareness of SDGs is important. Further efforts in collecting data for and use data of sustainable development, especially the SDGs, are essential. Emerging trend of studying the interactions across SDGs reflects the future direction of relevant fields. Originality/value – This paper has high originality because it is an early-stage research in the SDG interactions in Sub-Sahara African countries with the perspective of gender, gender disparity, Sub-Sahara Africa, SDGs, ALO and rural education attainments. This paper has both academic and practical values because of its innovative research thoughts and policy-oriented implications.

Abstract Triple negative breast cancer (TNBC) is a disease of poor prognosis, with the majority classified as the basal-like subtype associated with epithelial-mesenchymal transition and metastasis. Because basal breast cancers originate from proliferative luminal progenitor-like cells upon dysregulation of proper luminal differentiation, genes regulating luminal-basal transition are critical to elucidate novel therapeutic targets to improve TNBC outcomes. Herein we demonstrate that the tumor suppressor DEAR1/TRIM62 is a critical regulator of luminal cell fate. DEAR1 loss in human mammary epithelial cells results in significantly enhanced mammosphere formation that is accelerated in the presence of TGF-β/SMAD3 signaling. Mammospheres formed following DEAR1 loss are enriched for ALDH1A1 and CK5 expression, EpCAM−/CD49f+ and CD44high/24low basal-like epithelial cells, indicating that DEAR1 regulates stem/progenitor cell properties and luminal-basal progenitor transition. We show that DEAR1 maintains luminal differentiation as a novel ubiquitin ligase for SNAI2/SLUG, a master regulator driving stemness and generation of basal-like progenitor populations. We also identify a significant inverse correlation between DEAR1 and SNAI2 expression in a 103 TNBC case cohort and show that low DEAR1 expression significantly correlates with young age of onset and shorter time to metastasis, suggesting DEAR1 could serve as a biomarker to stratify early onset TNBCs for targeted stem cell therapies.

Keypoints Elevated triglyceride and high-sensitive CRP are associated with a higher risk of acute leukemia in MDS.

Sustainable Development Goal (SDG) Indicator 14.7.1 is the only statistical indicator under the SDG framework which measures the progress to achieve sustainable fisheries. However, despite its advantages, it suffers from substantial limitations. One main problem is that it is ambiguous what this indicator really measures and what the definition of sustainable fisheries is, which is the core concept of SDG Indicator 14.7.1. In particular, this indicator has both an environmental dimension and an economic dimension, but it is unclear how one indicator can exactly reflect these two dimensions at the same time. In addition, while SDG Indicator 14.7.1 emphasizes inclusiveness in name, its definition, methodology, and practical application reveal the exclusion of a substantial number of countries from this indicator. These limitations not only diminish the anticipated functionality of SDG Indicator 14.7.1 but also contradict the objective of inclusivity. Such shortcomings of SDG Indicator 14.7.1 are possibly a result of the non-statistical considerations during the development of this indicator, including possible political influence on the statistical scientific process. A number of implications for improving the further development and use of this indicator are provided, such as the provision of more specific data and metadata

Black tea is a healthy and popular tea beverage. However, its main bioactive compounds (theaflavins and thearubigins) are not easily absorbed. The aim of this study was to investigate the modulation of intestinal microbiota by the nonabsorptive components of Keemun black tea (KBT) and Dianhong black tea (DBT), and fructooligosaccharide (FOS) was selected for use in the control group. KBT, DBT, and FOS significantly increased total short-chain acid production. Specifically, FOS treatment predominantly increased the production of acetic acids and black tea treatments increased the production of acetic, propionic, and butyric acids at similar rates. Moreover, FOS exerted a strong bifidogenic effect after 24 h of fermentation; KBT and DBT increased the abundance of the beneficial genus Bacteroides and Roseburia. In summary, the nonabsorptive components of KBT and DBT could serve as novel prebiotics, the underlying mechanisms of which are quite different from those of FOS.

Abstract Background Personalized and effective treatments for pancreatic ductal adenocarcinoma (PDAC) continue to remain elusive. Novel clinical trial designs that enable continual and rapid evaluation of novel therapeutics are needed. Here, we describe a platform clinical trial to address this unmet need. Methods This is a phase II study using a Bayesian platform design to evaluate multiple experimental arms against a control arm in patients with PDAC. We first separate patients into three clinical stage groups of localized PDAC (resectable, borderline resectable, and locally advanced disease), and further divide each stage group based on treatment history (treatment naïve or previously treated). The clinical stage and treatment history therefore define 6 different cohorts, and each cohort has one control arm but may have one or more experimental arms running simultaneously. Within each cohort, adaptive randomization rules are applied and patients will be randomized to either an experimental arm or the control arm accordingly. The experimental arm(s) of each cohort are only compared to the applicable cohort specific control arm. Experimental arms may be added independently to one or more cohorts during the study. Multiple correlative studies for tissue, blood, and imaging are also incorporated. Discussion To date, PDAC has been treated as a single disease, despite knowledge that there is substantial heterogeneity in disease presentation and biology. It is recognized that the current approach of single arm phase II trials and traditional phase III randomized studies are not well-suited for more personalized treatment strategies in PDAC. The PIONEER Panc platform clinical trial is designed to overcome these challenges and help advance our treatment strategies for this deadly disease. Trial registration This study is approved by the Institutional Review Board (IRB) of MD Anderson Cancer Center, IRB-approved protocol 2020-0075. The PIONEER trial is registered at the US National Institutes of Health (ClinicalTrials.gov) NCT04481204 .

Both child mortality and water stress are included into the Sustainable Development Goals (SDGs). Existing studies have explored the relationship between child mortality and water stress with different perspectives, however, the results vary due to differences in methods and context. There is still insufficient cross-country comparative research on the association between child mortality and water stress under the framework of SDGs. This article uses data of 20 developing countries to explore the association between child mortality and water stress, based on the path analysis methodology. The results show that in term of statistics, the level of water stress is negatively but insignificantly associated with child mortality in developing countries. This unconventional result is explained by a number of possible reasons such as high reliance on food importation in some developing countries, and also the indirect link between water stress and child mortality via a country’s socioeconomic development (measured by national poverty rate). The results enrich scientific knowledge of and provide practical implications to the interactions between SDGs.

Abstract DNA nanomachines with artificial intelligence have attracted great interest, which may open a new era of precision medicine. However, their in vivo behavior, including early diagnosis and therapeutic effect are limited by their targeting efficiency. Here, a tetrahedral DNA framework (TDF)‐based nanodevice for in vivo near‐infrared (NIR) diagnosis of early‐stage AKI is developed. This nanodevice comprises three functional modules: a size‐tunable TDF nanostructure as kidney‐targeting vehicle, a binding module for the biomarker kidney injury molecule‐1 (Kim‐1), and a NIR signaling module. The cooperation of these modules allows the nanodevice to be selectively accumulated in injured kidney tissues with high Kim‐1 level, generating strong NIR fluorescence; whereas the nanodevice with the proper size can be rapidly cleared in healthy kidneys to minimize the background. By using this nanodevice, the early diagnosis of AKI onset is demonstrated at least 6 h ahead of Kim‐1 urinalysis, or 12 h ahead of blood detection. It is envisioned that this TDF‐based nanodevice may have implications for the early diagnosis of AKI and other kidney diseases.

The chemical compositions of black teas differ greatly and may have different health benefits; however, systematic investigations into such benefits are lacking. Here, the chemical profiles of Keemun black tea (KBT) and Dianhong black tea (DBT), two common categories of tea in China, were analyzed, and their lipid-lowering effects in male C57BL/6 mice fed a high-fat diet (60% energy from fat) or the diet supplemented with 2% black tea powder for 15 weeks were investigated. The compounds most crucial in differentiating KBT and DBT were determined to be phenolic compounds, theanine, and D-psicose. DBT was more effective than KBT in preventing excess hepatic fat accumulation. Both black teas effectively and comparably altered the mRNA levels of hepatic lipid–metabolizing genes. DBT had more favorable effects in stimulating fecal fat excretion than did KBT. The differentiating compounds with the higher values of variable importance in the projection (VIP) might predominantly contribute to the different health benefits; however, the most essential compound or combination of compounds requires clarification.

This article describes the R package BOIN, which implements a recently developed methodology for designing single-agent and drug-combination dose-finding clinical trials using Bayesian optimal interval designs (Liu and Yuan 2015; Yuan, Hess, Hilsenbeck, and Gilbert 2016). The BOIN designs are novel "model-assisted" phase I trial designs that can be implemented simply and transparently, similar to the 3 + 3 design, but yield excellent performance comparable to those of more complicated, model-based designs. The BOIN package provides tools for designing, conducting, and analyzing single-agent and drug-combination dose-finding trials.

Tourists’ perceived image is the core of destination marketing. As an important niche tourist destination, the analysis of tourists’ perceived image of tropical forest parks has great value. This study takes the Yalong Bay Tropical Paradise Forest Park as a case site and collects a total of 1,44,022 words from online travel reviews on Ctrip.com via the Python web crawler technology. Firstly, through high-frequency word analysis, we identified 77 core elements and a total of five image themes, which are attraction image, emotional image, service facility image, crowd image, and activity image. Secondly, building on Net Draw analysis, a network structure diagram of the tourist’ perceived image of the Yalong Bay Tropical Paradise Forest Park is constructed. Finally, the overall network and individual network of tourists’ perceived image are analyzed. The results indicate that low overall network density is in possession of core and periphery. Guojianglong Cable Bridge, battery car, and glass path enjoy both high degree centrality and betweenness centrality. They also show significant advantages of structural holes. Therefore, they are on the top of the network. The academic and practical value of tourism image projection and development in tropical forest park is discussed.

This article uses economic value added (EVA) to analyze the sustainability of performance of tourism listed companies from 2013 to 2015. The Malmquist index is used for the analysis of different operating performance across various types of tourism listed companies. It is found that the operating performance of tourism listed companies in China is not satisfactory, as merely less than half of them have a positive EVA. This study also finds that for different types of tourism listed companies, a variety of strategies for improvement should be adopted. For example, commercial companies should pay attention to the new customer needs, and scenic area companies need to increase investment in technology.

Background It is widely perceived that COVID-19 has significant influence on higher education and also contribution to development including Sustainable Development Goals (SDGs). However there is insufficient evidence about investigations on such influences, especially at micro level. Design and method A university located in Wuhan, China, was selected for the case study to explore how COVID-19 affects higher education and how universities’ coping strategies of COVID-19 can contribute to SDGs. The method is an analysis of 32 institutional documents published by the university. Results The university in the case study has taken a number of coping strategies of COVID-19, largely in four aspects including medical services, online education, logistic support, and graduate employment promotion. These coping strategies contribute to achieving SDGs, especially SDGs 1, 3, 4, 5, 8, and 10. Conclusions The case study provides micro-level empirical evidence, which supports that appropriate university coping strategies of COVID-19 can contribute to SDGs, even it is widely perceived that the pandemic has brought strong negative impact on higher education and sustainable development. The selection of a university in Wuhan, China can generate more practical implications, as Wuhan is the first city that experienced the unprecedented lockdown, and China is the first country which reopened university campuses after the lockdown.

First paragraph: The food supply has been disrupted by COVID-19. Shopping in supermarkets and grocery stores in the pandemic may not be a pleasant experience, as it can often lead to disappointment and anxiety since a lot of food items are not available or out of stock. The pandemic’s impact on the food supply has attracted attention from scholars and practitioners alike, and there have been many studies based on evidence from developing countries (e.g., Zurayk, 2020). However, there is still a lack of research based on the experiences of more developed and industrialized economies such as France and Germany. This is an important knowledge gap to be bridged, as people in developed countries tend to consume more food than those in developing countries (Delgado, 2003). Developed countries are also usually in the center of global food supply chains due to their stronger influence in trade. . . .

The concept of coherence was proposed for single-agent phase I clinical trials to describe the property that a design never escalates the dose when the most recently treated patient has toxicity and never de-escalates the dose when the most recently treated patient has no toxicity. It provides a useful theoretical tool for investigating the properties of phase I trial designs. In this paper, we generalize the concept of coherence to drug combination trials, which are substantially different and more challenging than single-agent trials. For example, in the dose-combination matrix, each dose has up to 8 neighboring doses as candidates for dose escalation and de-escalation, and the toxicity orders of these doses are only partially known. We derive sufficient conditions for a model-based drug combination trial design to be coherent. Our results are more general and relaxed than the existing results and are applicable to both single-agent and drug combination trials. We illustrate the application of our theoretical results with a number of drug combination dose-finding designs in the literature.

Abstract Background Sample size planning for longitudinal data is crucial when designing mediation studies because sufficient statistical power is not only required in grant applications and peer-reviewed publications, but is essential to reliable research results. However, sample size determination is not straightforward for mediation analysis of longitudinal design. Methods To facilitate planning the sample size for longitudinal mediation studies with a multilevel mediation model, this article provides the sample size required to achieve 80% power by simulations under various sizes of the mediation effect, within-subject correlations and numbers of repeated measures. The sample size calculation is based on three commonly used mediation tests: Sobel’s method, distribution of product method and the bootstrap method. Results Among the three methods of testing the mediation effects, Sobel’s method required the largest sample size to achieve 80% power. Bootstrapping and the distribution of the product method performed similarly and were more powerful than Sobel’s method, as reflected by the relatively smaller sample sizes. For all three methods, the sample size required to achieve 80% power depended on the value of the ICC (i.e., within-subject correlation). A larger value of ICC typically required a larger sample size to achieve 80% power. Simulation results also illustrated the advantage of the longitudinal study design. The sample size tables for most encountered scenarios in practice have also been published for convenient use. Conclusions Extensive simulations study showed that the distribution of the product method and bootstrapping method have superior performance to the Sobel’s method, but the product method was recommended to use in practice in terms of less computation time load compared to the bootstrapping method. A R package has been developed for the product method of sample size determination in mediation longitudinal study design.

Currently, surveillance strategies have inadequate performance for cirrhosis and early detection of hepatocellular carcinoma (HCC). The glycosylation of serum haptoglobin has shown to have significant differences between cirrhosis and HCC, thus can be used for diagnosis. We performed a comprehensive liquid chromatography—parallel reaction monitoring—mass spectrometry (LC-PRM-MS) approach, where a targeted parallel reaction monitoring (PRM) strategy was coupled to a powerful LC system, to study the site-specific isomerism of haptoglobin (Hp) extracted from cirrhosis and HCC patients. We found that our strategy was able to identify a large number of isomeric N-glycopeptides, mainly located in the Hp glycosylation site Asn207. Four N-glycopeptides were found to have significant changes in abundance between cirrhosis and HCC samples (p < 0.05). Strategic combinations of the significant N-glycopeptides, either with alpha-fetoprotein (AFP) or themselves, better estimate the areas under the curve (AUC) of their respective receiver operating characteristic (ROC) curves with respect to AFP. The combination of AFP with the isomeric sialylated fucosylated N-glycopeptides Asn207 + 5-6-1-2 and Asn207 + 5-6-1-3, resulted with an AUC value of 0.98, while the AUC value for AFP alone was 0.85. When comparing cirrhosis vs. early HCC, the isomeric N-glycopeptide Asn207 + 5-6-0-1 better estimated AUC with respect to AFP (AUCAFP = 0.81, and AUCAsn207 + 5-6-0-1 = 0.88, respectively).

The hospitalist model of care has gained favour in many hospital systems for the value, cost-effectiveness and quality of care that hospitalists provide. Hospitalists are experts in high-acuity medical problems of patients and they are intimately knowledgeable about hospital operations that enable efficiency of patient care. This results in tremendous cost-savings for institutions especially since hospitalists are also obligated to be involved in quality and practice improvement initiatives. The University of Texas MD Anderson Cancer Center employs oncology-hospitalists for many of their patients with cancer needing inpatient services. This physician team has expertise in both cancer-related and comorbidity-related reasons for hospitalisation. In September 2015, the thoracic and head and neck medical oncology team started a collaboration with the Oncology Hospitalist team whereby a proportion of patients with thoracic malignancies were directly admitted to hospitalists for inpatient care. To determine the value of this collaboration, a pre- and post- implementation study was done to compare quality outcomes such as readmission rates and length of stay (LOS) between the two groups. Adjusted outcomes showed that readmission rates were similar for both physician groups both at baseline and after implementation of the collaborative (p=0.680 and p=0.840, respectively). Median LOS was similar for both groups at baseline (4 days) and was not significantly different post-implementation (4vs5 days, p=0.07). The adjusted cost of a hospitalisation was also similar for hospitalist encounters and thoracic oncology encounters. This initial study showed that quality of care remained comparable for patients with lung cancer who were admitted to either service. With possibly shorter LOS but comparable readmission outcomes and adjusted cost for patients discharged from the hospitalist service, there is a strong value benefit for the implemented Thoracic Oncology-Hospitalist inpatient collaborative.