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Haoxin Guo,1,&ast; Wenbo Li,1,&ast; Kuan Wang,1,2 Zetong Nie,1 Xiang Zhang,1 Siqiong Bai,1 Naxin Duan,1 Xiaorong Li,1 Bojie Hu1 1Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin University Eye Hospital, Tianjin, People’s Republic of China; 2Cangzhou Eye Hospital, Cangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bojie Hu, Email bhu07@tmu.edu.cnPurpose: We aimed to investigate the risk factors associated with revitrectomy in eyes with diabetic vitreous hemorrhage and to determine the prognosis of these patients at least one year postoperatively.Patients and Methods: This retrospective case-control study had a minimum follow-up period of one year. Patients were divided into single vitrectomy group (control group, n=202) and revitrectomy group (case group, n=36) for analysis. The indications, number, and timing of revitrectomies were documented. And the revitrectomy group was further divided into two vitrectomies group (n=30) and three or more vitrectomies group (n=6). The best-corrected visual acuity (BCVA) at the last follow-up and the occurrence of neovascular glaucoma (NVG) were compared among the single vitrectomy, two vitrectomies and three or more vitrectomies groups. We conducted a thorough collection of patient data and used univariate and binary logistic regression analyses to identify the risk factors associated with revitrectomy.Results: A total of 197 patients (238 eyes) were included. Thirty-six eyes (15.1%) required revitrectomy with six eyes (2.5%) undergoing three or more vitrectomies during the follow-up period. The median duration of the second vitrectomy was 3 (2– 6) months. The indications for a second vitrectomy included 28 eyes (77.8%) of postoperative vitreous hemorrhage and 7 eyes (22.2%) combined with tractional retinal detachment. Patients undergoing three or more vitrectomies had significantly worse postoperative BCVA and a higher incidence of NVG (P< 0.01). Fibrinogen> 4 g/L (P< 0.001) and preoperative anti-vascular endothelial growth factor intravitreal injection (P=0.015) were independent risk factors for revitrectomy, and glycated hemoglobin A1c (HbA1c)> 10% (P=0.049) showed significant difference only in univariate analysis.Conclusion: Patients requiring revitrectomy tended to have higher fibrinogen levels, tightly adhered fibrovascular membranes, higher HbA1c levels, and worse prognoses.Keywords: proliferative diabetic retinopathy, vitreous hemorrhage, revitrectomy, fibrinogen, retinal ischemia

Hepatoma exhibits a series of heterogeneous subpopulations in its cell surface markers, tumorigenicity, invasion and metastatic capability. We previously demonstrated that the CD133(-)/EpCAM(-) hepatoma subpopulation was more metastatic than its counterpart; however, the controlling mechanisms are unexplored. The present study aimed to delineate the significance of aberrant hedgehog (Hh) signaling in the mediation of metastases. Fluorescence-activated cell sorting-enriched CD133(-)/EpCAM(-) (double negative, DN), Huh-7 cells underwent a transwell selection for metastatic cells (transwell-selected, TS). The TS cells displayed much greater metastatic activity as evidenced by an increased invasion rate, extremely upregulated expression of matrix metalloproteinase (MMP)-1/2/9 genes compared with DN and double-positive (DP) subpopulations. In contrast to DP cells, TS cells lost E-cadherin and were all vimentin-positive as shown by immunocytochemistry. There was a transitional increase in Gli-1/2 gene expression levels from DP, DN to TS subpopulations, which was consistent with elevated Gli-1/2 or Twist-1 protein levels in the nuclear fraction. Furthermore, truncated Gli-1 (tGli-1), which transactivates molecules involved in metastasis, was detected in the highly invasive Huh-7 cell subpopulation, but not in less metastatic hepatoma cells or normal hepatocytes. The enhanced metastatic features with increased expression of MMPs as well as the presence of twist and snail genes in TS Huh-7 cells were reversed by LDE225, a potent Smoothened antagonist. In conclusion, the highly metastatic capability of a unique TS subpopulation was highly attributed to significant epithelial-mesenchymal transition, enhanced Hh activity and aberrant occurrence of a tGli-1 variant, which appears to be responsible for the highly invasive behavior.

BACKGROUND: Chronic pain is prevalent, costly, and clinically vexatious. Clinicians typically use a trial-and-error approach to treatment selection. Repeated crossover trials in a single patient (n-of-1 trials) may provide greater therapeutic precision. N-of-1 trials are the most direct way to estimate individual treatment effects and are useful in comparing the effectiveness and toxicity of different analgesic regimens. The goal of the PREEMPT study is to test the 'Trialist' mobile health smartphone app, which has been developed to make n-of-1 trials easier to accomplish, and to provide patients and clinicians with tools for individualizing treatments for chronic pain. METHODS/DESIGN: A randomized controlled trial is being conducted to test the feasibility and effectiveness of the Trialist app. A total of 244 participants will be randomized to either the Trialist app intervention group (122 patients) or a usual care control group (122 patients). Patients assigned to the Trialist app will work with their clinicians to set up an n-of-1 trial comparing two pain regimens, selected from a menu of flexible options. The Trialist app provides treatment reminders and collects data entered daily by the patient on pain levels and treatment side effects. Upon completion of the n-of-1 trial, patients review results with their clinicians and develop a long-term treatment plan. The primary study outcome (comparing Trialist to usual care patients) is pain-related interference with daily functioning at 26 weeks. DISCUSSION: Trialist will allow patients and clinicians to conduct personalized n-of-1 trials. In prior studies, n-of-1 trials have been shown to encourage greater patient involvement with care, which has in turn been associated with better health outcomes. mHealth technology implemented using smartphones may offer an efficient means of facilitating n-of-1 trials so that more patients can benefit from this approach. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02116621 , first registered 15 April 2014.

Wenli Qiu,1 Na Duan,1 Xiao Chen,1 Shuai Ren,1 Yifen Zhang,2 Zhongqiu Wang,1 Rong Chen3 1Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2Department of Pathology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 3Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USACorrespondence: Zhongqiu WangDepartment of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Road, Nanjing 210029, Jiangsu Province, People’s Republic of ChinaTel +86 25 8661 8472Fax +86 25 8661 8139Email zhq200105@sina.comPurpose: To assess the performance of combining computed tomography (CT) texture analysis with machine learning for discriminating different histopathological grades of pancreatic ductal adenocarcinoma (PDAC).Methods: From July 2012 to August 2017, this retrospective study comprised 56 patients with confirmed histopathological PDAC (32 men, 24 women, mean age 64.04±7.82 years) who had undergone preoperative contrast-enhanced CT imaging within 1 month before surgery. Two radiologists blinded to the histopathological outcome independently segmented lesions for quantitative texture analysis. Histogram features, co-occurrence, and run-length texture were calculated. A support-vector machine was constructed to predict the pathological grade of PDAC based on preoperative texture features.Results: Pathological analysis confirmed 37 low-grade PDAC (five well-differentiated/grade I and 32 moderately differentiated/grade II) and 19 high-grade PDAC (19 poorly differentiated/grade III) tumors. There were no significant differences in clinical or biological characteristics between patients with high-grade and low-grade tumors (P>0.05). There were significant differences between low-grade PDAC and high-grade PDAC on nine histogram features, seven run-length features, and two co-occurrence features. Cluster shade was the most important predictor (sensitivity 0.315). Using these texture features, the support-vector machine achieved 86% accuracy, 78% sensitivity, 95% and specificity.Conclusion: Machine learning–based CT texture analysis accurately predicted histopathological differentiation grade of PDAC based on preoperative texture features, leading to maximization patient survival and achievement of personalized precision treatment.Keywords: computed tomography, texture analysis, machine learning, pancreatic ductal adenocarcinoma, histopathological grade

Nan Xiao,1,* Jianghui Yang,2,* Ning Duan,1 Binghuai Lu,3 Lijun Wang41Department of Laboratory Medicine, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing 102218, People’s Republic of China; 2Department of Pathology, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing 102218, People’s Republic of China; 3Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital; National Clinical Research Center of Respiratory Diseases, Beijing 100029, People’s Republic of China; 4Clinical Research Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, People’s Republic of China*These authors contributed equally to this workPurpose: Community-associated Staphylococcus aureus (CA S. aureus) is the most common causative pathogen of the skin and soft tissue infections (SSTIs). This study aims to determine clonal distribution, virulence factors of CA S. aureus clinical isolates from purulent SSTIs in Beijing, China.Materials and methods: CA-S. aureus isolates were collected from 115 outpatients with purulent SSTIs from the department of dermatology from April 2015 to April 2017. Multilocus sequence typing and Staphylococcus cassette chromosome mec typing were performed to explore molecular characteristics. Phylogenetic analysis of 16S rRNA of dominant S. aureus isolates was performed using MEGA-X software. Virulence genes were detected by PCR, while biofilm formation was evaluated by a microtiter plate method. The antimicrobial susceptibility was tested by an automatic VITEK system.Results: Forty-four CA-S. aureus isolates identified from SSTIs contain 9 methicillin-resistant S. aureus (MRSA) isolates (20.4%) and 35 methicillin-susceptible S. aureus isolates (MSSA) (79.6%). The dominant sequence types (STs) were ST22 (40.9%) and clonal complex 59 (CC59; 77.8%) in Community-associated methicillin resistant methicillin-resistant S. aureus. 27.8% of ST22 isolates were homologous to the epidemic ST22 EMRSA-15 in Europe. The prevalence of virulence genes lukS/lukF, tst-1, etA, edinA, icaA, and icaD was 50%, 93.2%, 4.5%, 4.5%, 100%, and 100%, respectively. All CC59 isolates exhibited stronger biofilm-forming capability than ST22 clones. Among the MSSA subgroup, the poor biofilm producers had significantly higher sensitivity to sulfamethoxazole/Trimethoprim.Conclusion: The dominant epidemic clone PVL+ ST22 MSSA containing tst-1 occurs in Beijing, indicating that a PVL+ ST398 clone which was previously predominant in this district had been replaced by a new clone.Keywords: community-associated Staphylococcus aureus, skin and soft tissue infection, biofilm formation, MLST-genotyping

Engaging consumers in prospectively shaping strategies for dissemination of health-care innovations may help to ensure acceptability. We examined the feasibility of using conjoint analysis to assess future HIV vaccine acceptability among three diverse communities: a multiethnic sample in Los Angeles, CA, USA (n = 143); a Thai resident sample in Los Angeles (three groups; n = 27) and an Aboriginal peoples sample in Toronto (n = 13). Efficacy had the greatest impact on acceptability for all three groups, followed by cross-clade protection, side-effects and duration of protection in the Los Angeles sample; side-effects and duration of protection in the Thai-Los Angeles sample; and number of doses and duration of protection in the Aboriginal peoples-Toronto sample. Conjoint analysis provided insights into universal and population-specific preferences among diverse end users of future HIV vaccines, with implications for evidence-informed targeting of dissemination efforts to optimize vaccine uptake.

Evidence-based medicine is the application of scientific evidence to clinical practice. This article discusses the difficulties of applying global evidence ("average effects" measured as population means) to local problems (individual patients or groups who might depart from the population average). It argues that the benefit or harm of most treatments in clinical trials can be misleading and fail to reveal the potentially complex mixture of substantial benefits for some, little benefit for many, and harm for a few. Heterogeneity of treatment effects reflects patient diversity in risk of disease, responsiveness to treatment, vulnerability to adverse effects, and utility for different outcomes. Recognizing these factors, researchers can design studies that better characterize who will benefit from medical treatments, and clinicians and policymakers can make better use of the results.

The ZrW2O8 family of materials are examined.