Abstract Background The purpose of this study was to compare patient outcomes between immediate breast reconstruction (IBR) after mastectomy and mastectomy alone. Methods We conducted a comprehensive ...literature search of PUBMED, EMBASE, Web of Science, and Cochrane Library. The primary outcomes evaluated in this review were overall survival, disease-free survival and local recurrence. Secondary outcome was the incidence of surgical site infection. All data were analyzed using Review Manager 5.3. Results Thirty-one studies, involving of 139,894 participants were included in this paper. Pooled data demonstrated that women who had IBR after mastectomy were more likely to experience surgical site infection than those treated with mastectomy alone (risk ratios 1.51, 95% CI: 1.22–1.87; p = 0.0001). There were no significant differences in overall survival (hazard ratios 0.92, 95% CI: 0.80–1.06; p = 0.25) and disease-free survival (hazard ratios 0.96, 95% CI: 0.84–1.10; p = 0.54) between IBR after mastectomy and mastectomy alone. No significant difference was found in local recurrence between two groups (risk ratios 0.92, 95% CI: 0.75–1.13; p = 0.41). Conclusions Our study demonstrates that IBR after mastectomy does not affect the overall survival and disease-free survival of breast cancer. Besides, no evidence shows that IBR after mastectomy increases the frequency of local recurrence.
The bryostatins, powerful protein kinase C (PKC) agonists, are a family of complex macrolactone natural products. They are originally isolated from the marine bryozoan Bugula neritina. So far tweenty ...bryostatins have been obtained naturally and exhibit a remarkable range of biological activities, including antineoplastic activity, synergistic chemotheoreputic activity, cognition and memory enhancement, etc. Of the 20 known members, the most extensively studied is bryostatin 1. The effects of bryostatin 1 are mainly linked to its ability of selectively modulating the function of various individual protein kinase C (PKC) isozymes. Moreover, bryostatin 1, or in combination with other agents, has been proposed for phase I and phase II clinical trials. The bryostatins have excellent biological properties, but are scarce in nature. Therefore, it has attracted considerable interests in structural modification over the past two decades. In this review, we will attempt to summarize the main developments that have occurred in the structure-activity relationship and biology of bryostatins over the period 1982-2011.
Abstract
Current approaches of using neural networks in lane departure warning systems are expensive. And it is difficult for neural networks to process 2K and 4K images. In this paper, we use a ...series of image preprocessing techniques such as perspective transformation, threshold processing and mask operation to process high-resolution images and the optimized sliding window method to fit the lane lines. Compared with neural network method, we can not only reduce hardware cost, but also quickly process high-resolution images. In addition, compared with the traditional lane line detection algorithm, we extract the region of interest through perspective transformation, which not only greatly reduces computation, but also converts images into an aerial view for subsequent processing. Especially, we carry out threshold operation and mask operation after perspective transformation, which greatly improves the performance of our algorithm in a strongly interfering environment. As can be seen from the experimental results, our method has good detection effect and can be applied to various road sections in different environments.
Cell-free DNA (cf-DNA)-based liquid biopsy is emerging as a revolutionary new method in individualized cancer treatment and prognosis monitoring, although detecting early-stage cancers using cf-DNA ...remains challenging, partially because of the undefined biological background of cf-DNA.
We investigated somatic mutations in the cf-DNA of 259 cancer-free individuals with a median age of 47 years using an endogenous barcoding duplex method with an ultralow base error rate (2 × 10−7) and compared the variant allele frequencies (VAFs) of these mutations between the cf-DNA and the corresponding blood cell DNA.
Sixty percent (155/259) of the samples showed at least one nonsynonymous mutation on either of two similar target panels covering 508 and 559 cancer-related genes. For individuals older than 50 years of age, the positive rate increased to 76%. Most cf-DNA mutations were also present at similar VAFs in the paired blood cell DNA. The most frequently mutated genes were driver genes of hematologic malignancies, including DNMT3A, TET2, AXSL1, and JAK2. However, the other 58.4% (192/329) of the mutations were likely ‘passenger mutations’ of clonal hematopoiesis, including mutations in NOTCH2, FAT3, EXT2, ERBB4, and ARID2, which are driver genes of solid tumors.
Hematopoietic clone-derived mutations, including ‘driver mutations’ and ‘passenger mutations’, are prevalent in the cf-DNA of both healthy individuals and cancer patients and may be a potential source of false positives in the liquid biopsy. Our results also suggest the ineffectiveness for distinguishing clonal hematopoietic mutations of low VAF (≤0.1%) from tumor-derived mutations using conventional next-generation sequencing of blood cell DNA. However, an error correction model with an ultralow error rate and high coverage depth is required for blood cell DNA sequencing, which is difficult and costly to achieve with current technologies.
Summary
Background
Atopic dermatitis is a systemic disorder characterized by abnormal barrier function across multiple organ sites. Causes of epidermal barrier breakdown are complex and driven by a ...combination of structural, genetic, environmental and immunological factors. In addition, alteration in microflora diversity can influence disease severity, duration, and response to treatment. Clinically, atopic dermatitis can progress from skin disease to food allergy, allergic rhinitis, and later asthma, a phenomenon commonly known as the atopic march. The mechanism by which atopic dermatitis progresses towards gastrointestinal or airway disease remains to be elucidated.
Objectives
This review addresses how epithelial dysfunction linking microbiome alteration and immune dysregulation can predispose to the development of the atopic march.
Methods
A literature search was conducted using the PubMed database for relevant articles with the keywords ‘atopic dermatitis’, ‘epithelial barrier’, ‘skin’, ‘gut’, ‘lung’, ‘microbiome’ and ‘immune dysregulation’.
Results
Initial disruption in the skin epidermal barrier permits allergen sensitization and colonization by pathogens. This induces a T helper 2 inflammatory response and a thymic stromal lymphopoietin‐mediated pathway that further promotes barrier breakdown at distant sites, including the intestinal and respiratory tract.
Conclusions
As there are no immediate cures for food allergy or asthma, early intervention aimed at protecting the skin barrier and effective control of local and systemic inflammation may improve long‐term outcomes and reduce allergen sensitization in the airway and gut.
What's already known about this topic?
The atopic march is a phenomenon characterized by sequential development of atopic dermatitis, food allergy, allergic rhinitis and later asthma; however, the mechanism by which atopic dermatitis progresses towards gastrointestinal or airway disease remains to be elucidated.
What does this study add?
This review addresses how epithelial dysfunction linking microbiome alteration and immune dysregulation can predispose to development of the atopic march.
We examine the factors contributing to the pathogenesis of the atopic march and propose strategies for intervention and targeted therapy.
Intermittent exotropia is the commonest type of strabismus, and surgery is the primary treatment. Follow-ups and other non-surgical management options can be used for patients who are younger, less ...cooperative, with well controlled exotropia, or unwilling to operate. However, there are many misconceptions regarding the treatment, especially the non-surgical treatment of intermittent exotropia in children, due to lack of thorough understanding about the natural course of intermittent exotropia, the timing for surgery, and the suitable candidates, effectiveness, and potential risks of different non-surgical options. This article provide an objective evaluation about the common non-surgical management options of intermittent exotropia based on the international research findings and clinical experience, in order to facilitate the correct understanding and rational use of the non-surgical treatment.
Literature review.
Spinal cord injury (SCI) remains a major public health issue in developed countries as well as worldwide. The pathophysiology of SCI is characterized by an initial primary injury ...followed by secondary deterioration. Although the etiology and pathogenesis of SCI remain to be fully understood, it has been suggested that reactive oxygen species (ROS) and oxidative stress have a significant role in the pathophysiology of SCI. Thus, alleviating oxidative stress may be an effective strategy for therapeutic intervention of SCI. The aim of this review was to describe (i) the sources of ROS as well as the major antioxidant defenses with particular attention being paid to lipid peroxidation; (ii) the biomarkers of oxidative stress in SCI and (iii) the neuroprotective effects of various compounds with antioxidative properties in animal models of SCI.
PubMed, one of the most comprehensive biomedical databases, was searched from 1976-2011. All relevant papers were read by title, abstract and full-length article.
Oxidative stress is considered a hallmark of injury of SCI. Thus, alleviating oxidative stress may be an effective way of therapeutic intervention of SCI. Two of these agents, the glucocorticoid steroid methylprednisolone and the non-glucocorticoid 21-aminosteroid tirilazad, have been shown to possess significant antioxidant activities and improve recovery of SCI patients in clinical trials. Other promising botanical compounds and their molecular targets and mechanisms of action with regard to potential protection against SCI were also described. These include carotenoids and phenolic compounds.
ROS and oxidative stress have a significant role in the pathophysiology of SCI. Alleviating oxidative stress is be an effective strategy for therapeutic intervention of SCI. Extensive research over the past several decades has identified numerous bioactive compounds that have antioxidative stress benefits in animal models of SCI. Thus, continued studies on bioactive compounds with ROS-scavenging capacity may lead to the development of effective antioxidant-based modalities for treating SCI in human subjects.
This paper develops a functional hybrid factor regression modelling framework to handle the heterogeneity of many large-scale imaging studies, such as the Alzheimer's disease neuroimaging initiative ...study. Despite the numerous successes of those imaging studies, such heterogeneity may be caused by the differences in study environment, population, design, protocols or other hidden factors, and it has posed major challenges in integrative analysis of imaging data collected from multicentres or multistudies. We propose both estimation and inference procedures for estimating unknown parameters and detecting unknown factors under our new model. The asymptotic properties of both estimation and inference procedures are systematically investigated. The finite-sample performance of our proposed procedures is assessed by using Monte Carlo simulations and a real data example on hippocampal surface data from the Alzheimer's disease study.
We propose a powerful scheme to accurately determine the formation energy and thermodynamic charge transition levels of point defects in nonmetals. Previously unknown correlations between defect ...properties and the valence-band width of the defect-free host material are identified allowing for a determination of the former via an accurate knowledge of the latter. These correlations are identified through a series of hybrid density-functional theory computations and an unbiased exploration of the parameter space that defines the Hyde-Scuseria-Ernzerhof family of hybrid functionals. The applicability of this paradigm is demonstrated for point defects in Si, Ge, ZnO, and ZrO2.
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