Abstract
BACKGROUND
Endometriosis is a benign gynaecological disease. Thus, it came as a complete surprise when it was reported recently that the majority of deep endometriosis lesions harbour ...somatic mutations and a sizeable portion of them contain known cancer-associated mutations (CAMs). Four more studies have since been published, all demonstrating the existence of CAMs in different subtypes of endometriosis. While the field is still evolving, the confirmation of CAMs has raised many questions that were previously overlooked.
OBJECTIVE AND RATIONALE
A comprehensive overview of CAMs in endometriosis has been produced. In addition, with the recently emerged understanding of the natural history of endometriotic lesions as well as CAMs in normal and apparently healthy tissues, this review attempts to address the following questions: Why has there been such a wild discrepancy in reported mutation frequencies? Why does ectopic endometrium have a higher mutation rate than that of eutopic endometrium? Would the presence of CAMs in endometriotic lesions increase the risk of cancer to the bearers? Why do endometriotic epithelial cells have much higher mutation frequencies than their stromal counterpart? What clinical implications, if any, do the CAMs have for the bearers? Do these CAMs tell us anything about the pathogenesis and/or pathophysiology of endometriosis?
SEARCH METHODS
The PubMed database was searched, from its inception to September 2019, for all papers in English using the term ‘endometriosis and CAM’, ‘endometriosis and cancer-driver mutation’, ‘somatic mutations’, ‘fibrosis’, ‘fibrosis and epigenetic’, ‘CAMs and tumorigenesis’, ‘somatic mutation and normal tissues’, ‘oestrogen receptor and fibrosis’, ‘oxidative stress and fibrosis’, ‘ARID1A mutation’, and ‘Kirsten rat sarcoma mutation and therapeutics’. All retrieved papers were read and, when relevant, incorporated into the review results.
OUTCOMES
Seven papers that identified CAMs in endometriosis using various sequencing methods were retrieved, and their results were somewhat different. Yet, it is apparent that those using microdissection techniques and more accurate sequencing methods found more CAMs, echoing recent discoveries that apparently healthy tissues also harbour CAMs as a result of the replicative aging process. Hence endometriotic lesions, irrespective of subtype, if left intact, would generate CAMs as part of replicative aging, oxidative stress and perhaps other factors yet to be identified and, in some rare cases, develop cancer. The published data still are unable to paint a clear picture on pathogenesis of endometriosis. However, since endometriotic epithelial cells have a higher turnover than their stromal counterpart due to cyclic bleeding, and since the endometriotic stromal component can be formed by refresh influx of mesenchymal cells through epithelial–mesenchymal transition, endothelial–mesenchymal transition, mesothelial–mesenchymal transition and other processes as well as recruitment of bone-marrow-derived stem cells and outflow due to smooth muscle metaplasia, endometriotic epithelial cells have much higher mutation frequencies than their stromal counterpart. The epithelial and stromal cellular components develop in a dependent and co-evolving manner. Genes involved in CAMs are likely to be active players in lesional fibrogenesis, and hyperestrogenism and oxidative stress are likely drivers of both CAMs and fibrogenesis. Finally, endometriotic lesions harbouring CAMs would conceivably be more refractory to medical treatment, due, in no small part, to their high fibrotic content and reduced vascularity and cellularity.
WIDER IMPLICATIONS
The accumulating data on CAMs in endometriosis have shed new light on the pathogenesis and pathophysiology of endometriosis. They also suggest new challenges in management. The distinct yet co-evolving developmental trajectories of endometriotic stroma and epithelium underscore the importance of the lesional microenvironment and ever-changing cellular identity. Mutational profiling of normal endometrium from women of different ages and reproductive history is needed in order to gain a deeper understanding of the pathogenesis. Moreover, one area that has conspicuously received scant attention is the epigenetic landscape of ectopic, eutopic and normal endometrium.
Given the severe global warming situation, it is very important to explore the factors influencing carbon emission intensity and accurately analyze the trends in the development of carbon emission ...intensity to achieve the goal of reducing carbon emissions. In contrast with the existing research, this paper starts from the perspective of carbon emission efficiency, applies stochastic frontier analysis to screen the factors influencing carbon intensity, and constructs a model for predicting carbon emission intensity based on factor analysis and an extreme learning machine. The results suggest that, first, there is a high correlation between carbon emission efficiency and carbon emission intensity. Second, the level of economic development, industrial structure, urbanization level, and government intervention all promote a reduction in carbon emission intensity. The structure of energy consumption and dependence on foreign trade restrain reductions in carbon emission intensity. Finally, the proposed model accurately predicts carbon emission intensity. The research results provide theoretical support for the development of technologies to reduce carbon emissions. This idea can be applied to predict carbon emission intensity in different regions and has practical significance.
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•Carbon efficiency is related to carbon intensity.•Indicators of carbon efficiency work in reverse on carbon intensity.•Energy consumption and foreign trade restrain the reduction of carbon intensity.•Economic, industrial, urbanization and government promote the reduction.
Tandem catalysis is a promising way to break the limitation of linear scaling relationship for enhancing efficiency, and the desired tandem catalysts for electrochemical CO2 reduction reaction ...(CO2RR) are urgent to be developed. Here, a tandem electrocatalyst created by combining Cu foil (CF) with a single‐site Cu(II) metal–organic framework (MOF), named as Cu–MOF–CF, to realize improved electrochemical CO2RR performance, is reported. The Cu–MOF–CF shows suppression of CH4, great increase in C2H4 selectivity (48.6%), and partial current density of C2H4 at −1.11 V versus reversible hydrogen electrode. The outstanding performance of Cu–MOF–CF for CO2RR results from the improved microenvironment of the Cu active sites that inhibits CH4 production, more CO intermediate produced by single‐site Cu–MOF in situ for CF, and the enlarged active surface area by porous Cu–MOF. This work provides a strategy to combine MOFs with copper‐based electrocatalysts to establish high‐efficiency electrocatalytic CO2RR.
A tandem electrocatalyst Cu–MOF–CF by combining Cu foil with Cu–MOF is developed to realize improved C2H4 product selectivity for CO2RR, which is attributed to the improved microenvironment of the Cu active sites that inhibits CH4 production, more CO intermediate produced by single‐site Cu–MOF for CF, and the enlarged active surface area by porous Cu–MOF.
Insight into COVID-19 intensive care unit (ICU) patient characteristics, rates and risks of invasive mechanical ventilation (IMV) and associated outcomes as well as any regional discrepancies is ...critical in this pandemic for individual case management and overall resource planning.
Electronic searches were performed for reports through May 1 2020 and reports on COVID-19 ICU admissions and outcomes were included using predefined search terms. Relevant data was subsequently extracted and pooled using fixed or random effects meta-analysis depending on heterogeneity. Study quality was assessed by the NIH tool and heterogeneity was assessed by I2 and Q tests. Baseline patient characteristics, ICU and IMV outcomes were pooled and meta-analyzed. Pooled odds ratios (pOR) were calculated for clinical features against ICU, IMV mortality. Subgroup analysis was carried out based on patient regions. A total of twenty-eight studies comprising 12,437 COVID-19 ICU admissions from seven countries were meta-analyzed. Pooled ICU admission rate was 21% 95% CI 0.12-0.34 and 69% of cases needed IMV 95% CI 0.61-0.75. ICU and IMV mortality were 28.3% 95% CI 0.25-0.32, 43% 95% CI 0.29-0.58 and ICU, IMV duration was 7.78 95% CI 6.99-8.63 and 10.12 95% CI 7.08-13.16 days respectively. Besides confirming the significance of comorbidities and clinical findings of COVID-19 previously reported, we found the major correlates with ICU mortality were IMV pOR 16.46, 95% CI 4.37-61.96, acute kidney injury (AKI) pOR 12.47, 95% CI 1.52-102.7, and acute respiratory distress syndrome (ARDS) pOR 6.52, 95% CI 2.66-16.01. Subgroup analyses confirm significant regional discrepancies in outcomes.
This is a comprehensive systematic review and meta-analysis of COVID-19 ICU and IMV cases and associated outcomes. The significant association of AKI, ARDS and IMV with mortality has implications for ICU resource planning for AKI and ARDS as well as suggesting the need for further research into optimal ventilation strategies for COVID-19 patients in the ICU setting. Regional differences in outcome implies a need to develop region specific protocols for ventilatory support as well as overall treatment.
Superalkalis are clusters or molecules featuring lower ionization energies (IEs) than that of cesium atoms, and thus exhibit excellent reducing properties. Such special species have great potential ...to be used in the synthesis of unusual charge‐transfer salts and cluster‐assembled nanomaterials with tailored properties, in the reduction of carbon dioxide, or as hydrogen storage materials and noble‐gas‐trapping agents, etc. In this regard, ongoing efforts have been devoted to designing and characterizing superalkalis of new types. The recent progress on the study of superalkalis in terms of theoretical design, characterization, and potential application is summarized in this minireview. We hope this review will not only provide a broad overview of this research field, but also highlight the prospect of further extending the experimental synthesis and practical application of superalkalis.
Alkalis with super powers: Superalkalis, as special species featuring excellent reducing ability, have received increasing research interest in recent years. This minireview summarizes the recent progress made in the design, characterization, and application of superalkalis.
Traditionally viewed as enigmatic and elusive, adenomyosis is a fairly common gynecological disease but is under-recognized and under-researched. This review summarizes the latest development on the ...pathogenesis and pathophysiology of adenomyosis, which have important implications for imaging diagnosis of the disease and for the development of non-hormonal therapeutics.
Traditionally considered as an enigmatic disease, adenomyosis is a uterine disease that affects many women of reproductive age and is a contributing factor for pelvic pain, heavy menstrual bleeding (HMB), and subfertility. In this review, the new development in the pathogenesis and pathophysiology of adenomyosis has been summarized, along with their clinical implications. After reviewing the progress in our understanding of the pathogenesis and describing the prevailing theories, in conjunction with their deficiencies, a new hypothesis, called endometrial-myometrial interface disruption (EMID), which is backed by extensive epidemiologic data and demonstrated by a mouse model, is reviewed, along with recent data implicating the role of Schwann cells in the EMI area in the genesis of adenomyosis. Additionally, the natural history of adenomyotic lesions is elaborated and underscores that, in essence, adenomyotic lesions are fundamentally wounds undergoing repeated tissue injury and repair (ReTIAR), which progress to fibrosis through epithelial-mesenchymal transition, fibroblast-to-myofibroblast transdifferentiation, and smooth muscle metaplasia. Increasing lesional fibrosis propagates into the neighboring EMI and endometrium. The increased endometrial fibrosis, with ensuing greater tissue stiffness, results in attenuated prostaglandin E2, hypoxia signaling and glycolysis, impairing endometrial repair and causing HMB. Compared with adenomyosis-associated HMB, the mechanisms underlying adenomyosis-associated pain are less understood but presumably involve increased uterine contractility, hyperinnervation, increased lesional production of pain mediators, and central sensitization. Viewed through the prism of ReTIAR, a new imaging technique can be used to diagnose adenomyosis more accurately and informatively and possibly help to choose the best treatment modality.
Abstract
In the field of transformer fault diagnosis, there are many diagnostic methods. These diagnostic methods are either not high accuracy or are used too long. In this paper, a dimension ...learning-based hunting (DLH) search strategy optimization grey wolf algorithm support vector machine (DLH-GWO-SVM) model was proposed. In the process of initializing the grey wolf population, logistic chaotic mapping was used to improve the quality of the initial wolf position. In the Wolf screening process, the DLH search strategy was adopted to solve the problem that GWO was prone to fall into the local optimal solution, and the improved Grey wolf algorithm (IGWO) was formed. Finally, the transformer fault types were classified by support vector machine (SVM), and IGWO was used to optimize the penalty factor and kernel parameter (g) of the SVM. Through the experimental analysis, the accuracy of transformer fault diagnosis can reach 95.83% after the application of the DLH-GWO-SVM model.
Adenomyosis is used to be called endometriosis interna, and deep endometriosis is now called adenomyosis externa. Thus, there is a question as to whether adenomyosis is simply endometriosis of the ...uterus, either from the perspective of pathogenesis or pathophysiology. In this manuscript, a comprehensive review was performed with a literature search using PubMed for all publications in English, related to adenomyosis and endometriosis, from inception to June 20, 2019. In addition, two prevailing theories, i.e., invagination-based on tissue injury and repair (TIAR) hypothesis-and metaplasia, on adenomyosis pathogenesis, are briefly overviewed and then critically scrutinized. Both theories have apparent limitations, i.e., difficulty in falsification, explaining existing data, and making useful predictions. Based on the current understanding of wound healing, a new hypothesis, called endometrial-myometrial interface disruption (EMID), is proposed to account for adenomyosis resulting from iatrogenic trauma to EMI. The EMID hypothesis not only highlights the more salient feature, i.e., hypoxia, at the wounding site, but also incorporates epithelial mesenchymal transition, recruitment of bone-marrow-derived stem cells, and enhanced survival and dissemination of endometrial cells dispersed and displaced due to iatrogenic procedures. More importantly, the EMID hypothesis predicts that the risk of adenomyosis can be reduced if certain perioperative interventions are performed. Consequently, from a pathogenic standpoint, adenomyosis is not simply endometriosis of the uterus, and, as such, may call for interventional procedures that are somewhat different from those for endometriosis to achieve the best results.
•Recent advancements in enhanced microchannels and their fabrication methods are reviewed•Four types of enhanced microchannels and their enhancement performance have been identified•Typical ...fabrication methods for enhanced microchannels has been discussed•Insights and recommendations on future directions of enhanced microchannels have been proposed
Rapid increase in heat fluxes within a small area in microelectronic, defense, energy, solar and medical components has spurred an urgent need for two-phase microchannel heat sinks due to their large heat transfer area to volume ratios, compact heat sink size, and high heat transfer coefficient (HTC). Nevertheless, underlying problems of large wall superheat for onset of nucleate boiling, inherent flow instability and low values of critical heat flux of flow boiling in conventional solid parallel microchannels pose severe challenges for practical applications of microchannel heat sinks in high heat flux dissipations. To address the above issue, numerous efforts have been taken to the design and fabrication of enhanced microchannels for flow boiling enhancement of two-phase microchannel heat sinks in recent years. To overview this subject, recent advancements in flow boiling enhancement and fabrication of enhanced microchannels are comprehensively reviewed in this paper. To the best knowledge of the authors’, it is the first time to present the advancements of enhanced microchannels from the fabrication perspective, which is critical for the application and commercialization of enhanced microchannel heat sinks. The enhanced microchannels are classified into flow disruption structures, reentrant cavity structures, porous structures, and nanostructures. Emphasis is on the flow boiling enhancement performance of these enhanced microchannels in microchannel heat sinks. Subsequently, typical fabrication methods for enhanced microchannels are summarized together with the discussion of their advantages and disadvantages, such as etching, micro-mechanical cutting, micro electrical discharge machining, laser processing, sintering, chemical vapor deposition and 3D printing. Finally, the challenges and future research directions of enhanced microchannels are reasonably clarified.
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