Abstract The aim of this study was to identify the risk factors for free flap failure after head and neck reconstructive surgery. The data of 881 consecutive patients who underwent free flap surgery ...at the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, between January 2013 and November 2016, were reviewed retrospectively. All surgeries were performed by a single head and neck surgical team. Patient demographic and surgical data that may have an influence on free flap outcomes were recorded. The χ2 test and multivariate logistic regression analysis were used to identify relevant risk factors. In total, 881 free tissue transfer surgeries were included in this study. Free flap failure occurred in 26 of 881 flaps (2.9%). A history of irradiation (odds ratio 0.205, 95% confidence interval 0.07–0.56; P = 0.002) was a statistically significant risk factor for free flap failure. Age, diabetes mellitus, history of previous neck surgery to the anastomosis side, donor site, choice of recipient vein, use of a coupler device, and postoperative anticoagulation were not associated with free flap outcomes. Thus, it is concluded that when performing head and neck reconstructive surgery, special attention should be paid to patients who have previously undergone irradiation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
ABSTRACT
We present results from the search for a stochastic gravitational-wave background (GWB) as predicted by the theory of General Relativity using six radio millisecond pulsars from the Data ...Release 2 (DR2) of the European Pulsar Timing Array (EPTA) covering a timespan up to 24 yr. A GWB manifests itself as a long-term low-frequency stochastic signal common to all pulsars, a common red signal (CRS), with the characteristic Hellings-Downs (HD) spatial correlation. Our analysis is performed with two independent pipelines, ENTERPRISE, and TEMPONEST+FORTYTWO, which produce consistent results. A search for a CRS with simultaneous estimation of its spatial correlations yields spectral properties compatible with theoretical GWB predictions, but does not result in the required measurement of the HD correlation, as required for GWB detection. Further Bayesian model comparison between different types of CRSs, including a GWB, finds the most favoured model to be the common uncorrelated red noise described by a power law with $A = 5.13_{-2.73}^{+4.20} \times 10^{-15}$ and $\gamma = 3.78_{-0.59}^{+0.69}$ (95 per cent credible regions). Fixing the spectral index to γ = 13/3 as expected from the GWB by circular, inspiralling supermassive black hole binaries results in an amplitude of $A =2.95_{-0.72}^{+0.89} \times 10^{-15}$. We implement three different models, BAYESEPHEM, LINIMOSS, and EPHEMGP, to address possible Solar system ephemeris (SSE) systematics and conclude that our results may only marginally depend on these effects. This work builds on the methods and models from the studies on the EPTA DR1. We show that under the same analysis framework the results remain consistent after the data set extension.
Background
Semenogelin 1 (SEMG1) is an important secretory protein in spermatozoa involved in the formation of a gel matrix encasing ejaculated spermatozoa. Previous studies show that the SEMG1 gene ...is highly expressed in spermatozoa from patients with asthenozoospermia (AZS); however, the underlying molecular mechanisms are not yet clear.
Objectives
To study the molecular mechanism of high expression of SEMG1 gene and its potential roles in AZS.
Materials and Methods
Western blot and real‐time PCR were used to detect the expression levels of SEMG1 protein and mRNA in the ejaculated spermatozoa from normozoospermic males and AZS patients. Bioinformatics analysis was used to predict miRNAs targeting for SEMG1 3′‐untranslated region detection of the expression levels of all the candidate miRNAs in ejaculatory spermatozoa in AZS patients or normozoospermic volunteers. Luciferase reporter assays were performed to confirm it can directly bind to SEMG1. Correlation of miR‐525‐3p and SEMG1 mRNA expression with clinical sperm parameters were also analyzed. Finally, we conducted a follow‐up study of reproductive history about all the subjects.
Results
SEMG1 mRNA and protein level were significantly higher in AZS patients compared to that in normozoospermic volunteers (p < 0.001). Subsequently, microRNA‐525‐3p (miR‐525‐3p) which was predicted as a candidate regulator of SEMG1 was found lower expressed in ejaculatory spermatozoa in AZS patients (p = 0.0074). Luciferase experiment revealed that microRNA‐525‐3p could directly target SEMG1 3′‐untranslated region and suppress its expression. Importantly, our retrospective follow‐up study showed that both low miR‐525‐3p expression and high SEMG1 expression level was significantly associated with low progressive sperm motility, abnormal sperm morphology, and infertility.
Discussion and Conclusion
The elevated expression of SEMG1 and reduced expression of miR‐525‐3p are associated with AZS and male infertility. Our study provides a potential therapeutic target for the treatment of male infertility or for male contraception.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Leptomeningeal metastases (LM) are more frequent in non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Due to limited access to leptomeningeal lesions, the ...purpose of this study was to explore the potential role of cerebrospinal fluid (CSF) as a source of liquid biopsy in patients with LM.
Primary tumor, CSF, and plasma in NSCLC with LM were tested by next-generation sequencing. In total, 45 patients with suspected LM underwent lumbar puncture, and those with EGFR mutations diagnosed with LM were enrolled.
A total of 28 patients were enrolled in this cohort; CSF and plasma were available in 26 patients, respectively. Driver genes were detected in 100% (26/26), 84.6% (22/26), and 73.1% (19/26) of samples comprising CSF cell-free DNA (cfDNA), CSF precipitates, and plasma, respectively; 92.3% (24/26) of patients had much higher allele fractions in CSF cfDNA than the other two media. Unique genetic profiles were captured in CSF cfDNA compared with those in plasma and primary tissue. Multiple copy number variations (CNVs) were mainly identified in CSF cfDNA, and MET copy number gain identified in 47.8% (11/23) of patients was the most frequent one, while other CNVs included ERBB2, KRAS, ALK, and MYC. Moreover, loss of heterozygosity (LOH) of TP53 was identified in 73.1% (19/26) CSF cfDNA, which was much higher than that in plasma (2/26, 7.7%; P<0.001). There was a trend towards a higher frequency of concomitant resistance mutations in patients with TP53 LOH than those without (70.6% versus 33.3%; P=0.162). EGFR T790M was identified in CSF cfDNA of 30.4% (7/23) of patients who experienced TKI progression.
CSF cfDNA could reveal the unique genetic profiles of LM and should be considered as the most representative liquid biopsy medium for LM in EGFR-mutant NSCLC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This study was performed to compare the effects of neck dissection procedures on the prognosis of patients with pathological N1 (pN1) oral squamous cell carcinoma (OSCC), analyse factors affecting ...the prognosis, and provide a neck management strategy for clinical N1 (cN1) oral cancer. The study patients were divided into two groups according to the neck dissection: a selective neck dissection (SND) group (n = 85) and a radical or modified radical neck dissection (RND/MRND) group (n = 22). There was no statistically significant difference in recurrence rates at local, regional, and distant sites between the SND and RND/MRND groups. The 5-year overall survival was 68.3% for SND and 65.2% for RND/MRND patients (P = 0.590), while the 5-year disease-specific survival was 70.4% for SND and 75.7% for RND/MRND patients (P = 0.715). Histological grade and postoperative radiotherapy were independent predictors of the outcome for SND patients. For histological grade II/III cases, 5-year overall survival (P = 0.004) and disease-specific survival (P = 0.002) outcomes differed significantly between patients treated with and without postoperative radiotherapy, with worse survival for patients not treated with radiotherapy. Therefore, SND appears appropriate for cN1 OSCC patients, and postoperative radiotherapy is recommended for those with histological grade II or III tumours.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We show that a high-energy electron bunch can be used to capture the instantaneous longitudinal and transverse field structures of the highly transient, microscopic, laser-excited relativistic wake ...with femtosecond resolution. The spatiotemporal evolution of wakefields in a plasma density up ramp is measured and the reversal of the plasma wake, where the wake wavelength at a particular point in space increases until the wake disappears completely only to reappear at a later time but propagating in the opposite direction, is observed for the first time by using this new technique.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
ABSTRACT
The European Pulsar Timing Array (EPTA) collaboration has recently released an extended data set for six pulsars (DR2) and reported evidence for a common red noise signal. Here we present a ...noise analysis for each of the six pulsars. We consider several types of noise: (i) radio frequency independent, ‘achromatic’, and time-correlated red noise; (ii) variations of dispersion measure and scattering; (iii) system and band noise; and (iv) deterministic signals (other than gravitational waves) that could be present in the PTA data. We perform Bayesian model selection to find the optimal combination of noise components for each pulsar. Using these custom models we revisit the presence of the common uncorrelated red noise signal previously reported in the EPTA DR2 and show that the data still supports it with a high statistical significance. Next, we confirm that there is no preference for or against the Hellings–Downs spatial correlations expected for the stochastic gravitational-wave background. The main conclusion of the EPTA DR2 paper remains unchanged despite a very significant change in the noise model of each pulsar. However, modelling the noise is essential for the robust detection of gravitational waves and its impact could be significant when analysing the next EPTA data release, which will include a larger number of pulsars and more precise measurements.
Summary
Exosomes are membranous nanovesicles of endocytic origin that carry and transfer regulatory bioactive molecules and mediate intercellular communication between cells and tissues. Although ...seminal exosomes have been identified in human seminal plasma, their exact composition and possible physiologic function remain unknown. The objective of this study was to perform a comprehensive proteomics analysis of exosomes derived from human seminal plasma. Seminal exosomes were isolated and purified from 12 healthy donors using a 30% sucrose cushion‐based exosome‐isolation protocol, followed by characterization by western blot, transmission electron microscopy, and nanoparticle tracking analysis before performing extensive liquid chromatography tandem mass spectrometry proteomics analysis. The identified proteins were analyzed by bioinformatics analysis, and seminal exosomes‐associated proteins were selectively validated by western blot. A total of 1474 proteins were identified in all seminal exosomes samples, with Gene Ontology analysis demonstrating that these identified seminal exosomes‐associated proteins were mostly linked to ‘exosomes,’ ‘cytoplasm,’ and ‘cytosol.’ Bioinformatics analysis indicated that these proteins were mainly involved in biologic processes, including metabolism, energy pathways, protein metabolism, cell growth and maintenance, and transport. Of these identified proteins, PHGDH, LGALS3BP, SEMG1, ACTB, GAPDH, and the exosomal‐marker protein ALIX were validated by western blot. This study provided a more comprehensive description of the seminal exosomes proteome and could also be a resource for further screening of biomarkers and comparative proteomics studies, including those associated with male infertility and prostate cancer.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The uplift of the Tibetan plateau, an area that is 2,000 km wide, to an altitude of about 5,000 m has been shown to modify global climate and to influence monsoon intensity. Mechanical and thermal ...models for homogeneous thickening of the lithosphere make specific predictions about uplift rates of the Tibetan plateau, but the precise history of the uplift of the plateau has yet to be confirmed by observations. Here we present well-preserved fossil leaf assemblages from the Namling basin, southern Tibet, dated to ∼15 Myr ago, which allow us to reconstruct the temperatures within the basin at that time. Using a numerical general circulation model to estimate moist static energy at the location of the fossil leaves, we reconstruct the elevation of the Namling basin 15 Myr ago to be 4,689 ± 895 m or 4,638 ± 847 m, depending on the reference data used. This is comparable to the present-day altitude of 4,600 m. We conclude that the elevation of the southern Tibetan plateau probably has remained unchanged for the past 15 Myr.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
► We investigated functionalized NGO for cancer targeted chemo-photothermal therapy. ► We developed FA–NGO–PVP loading with doxorubicine (DOX). ► FA–NGO–PVP was proved to be an ideal pH-responsive ...nanocarrier. ► We investigated the cell death induced by FA–NGO–PVP/DOX with 808nm laser in vitro. ► FA–NGO–PVP/DOX under laser irradiation shown an excellent anticancer efficacy.
Nanographene oxide (NGO), a new type of nanomaterial for anticancer drugs delivery and near-infrared (NIR)-mediated photothermal ablation of tumors, has been used in the combination of photothermal therapy and chemotherapy. Herein, targeted chemo-photothermal therapy based on polyvinylpyrrolidone (PVP) functionalized NGO was achieved. Folic acid (FA), a common target molecule to cancer cells, was conjugated to NGO via covalent amide bond. The obtained FA–NGO–PVP was proved to be an ideal pH-responsive nanocarrier for delivery of an anticancer drug doxorubicin (DOX) with the loading ratio more than 100%. In vitro experiments were then performed with the combination of chemotherapy and NIR photothermal therapy. The results demonstrated that the targeted chemo-photothermal therapy could specifically deliver drug and heat to tumor sites and showed excellent efficacy of anticancer therapy. Thus, FA–NGO–PVP could be used as a novel nanomaterial for selective chemo-photothermal therapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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