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关键词： Exfoliative glaucoma   Ganglion cell-inner plexiform layer thickness   Optical coherence tomography   Primary open-angle glaucoma   Retina nerve fiber layer thickness  

摘要： Purpose: To determine and compare the thickness of the ganglion cell-inner plexiform layer (GCIPL), the thickness of the retina nerve fiber layer (RNFL), and the parameters of the optic nerve head (ONH) in exfoliative glaucoma (XFG), primary open-angle glaucoma (POAG), and control eyes using optical coherence tomography (OCT). Methods: The study was a retrospective observational cross-sectional study of 43 eyes of patients with XFG, 44 eyes of patients with POAG, and 37 eyes of healthy participants. Visual acuity, intraocular pressure, central corneal thickness, rim-area, disc-area, average cup/disc ratio, vertical cup/disc ratio, cup volume, average RNFL thickness, and GCIPL (average, minimum, superior, superotemporal, superonasal, inferior, inferotemporal, and inferonasal) thicknesses were determined. Results: RNFL thicknesses were similar in the XFG and POAG groups (p = 0.065), and both glaucoma groups had significantly thinner RNFLs than the controls (p = 0.002). The XFG group had significantly thinner average and minimum GCIPLs compared to the POAG and control groups (p = 0.027, p < 0.001 for average thickness and p = 0.038, p < 0.001 for minimum thickness, respectively). No significant difference was found in the ONH parameters among the three groups except for rim-area and cup volume (p > 0.05 for all ONH parameters, p < 0.001 for rim-area, and p = 0.003 for cup volume). Mean visual field mean deviation was -11.6 +/- 8.2 dB in the XFG group and -10.4 +/- 9.3 dB in the POAG group (p = 0.453). Conclusion: Eyes with XFG were found to have a thinner GCIPL (minimum and average) than eyes with POAG or from healthy controls, although the RNFL measurements were similar to those of eyes with POAG. GCIPL thickness may be a more valuable indicator than RNFL thickness in patients with XFG for early detection of glaucoma and/or for glaucoma progression measurement. There is still some debate in the literature about whether decreases in GCIPL thickness and RNFL thickness (

关键词： Non-small cell lung cancer   Programmed cell death-1   Bullae   Checkpoint inhibitor  

摘要： Background Immune checkpoint inhibitors (ICIs) have become a standard therapy in non-small cell lung cancer (NSCLC). Although lung cancer adjoining emphysematous bullae (Ca-ADJ) were reported to express higher programmed cell death-ligand 1 (PD-L1), the predictive impact of Ca-ADJ on the response to ICIs is unknown. Methods Two hundred and fifty-seven advanced or recurrent NSCLC patients treated with ICI monotherapy at Kyushu University Hospital and National Hospital Organization Kyushu Cancer Center were analyzed. To minimize the bias arising from the patients' background, adjusted Kaplan-Meier survival curves and Cox proportional hazards regression analyses using inverse probability of treatment weights (IPTW) were performed. Results Of the 257 patients, 55 had Ca-ADJ. Patients with Ca-ADJ were significantly associated with younger age (P = 0.0343), male sex (P = 0.0070), and smoking (P = 0.0080). The objective response rate of cases with Ca-ADJ was significantly higher than that of those without Ca-ADJ (36.4% vs. 20.8%, respectively;P = 0.0167). The disease control rate of cases with Ca-ADJ was also significantly higher than tumors without Ca-ADJ (63.6% vs. 47.5%, respectively;P = 0.0341). The IPTW-adjusted Kaplan-Meier curves showed that patients with Ca-ADJ had significantly longer progression-free survival (PFS) and overall survival (OS) than those without Ca-ADJ (P = 0.0407 and P = 0.0126, respectively). On IPTW-adjusted Cox analysis, Ca-ADJ was an independent predictor of PFS and OS (P < 0.0001 and P < 0.0001, respectively). Conclusions Patients with Ca-ADJ may be good candidates for ICIs. These findings should be validated prospectively.

关键词： Merkel cell carcinoma   PD-L1   IDO1   CD8   FoxP3  

摘要： The association of immune markers and clinicopathologic features and patient outcome has not been extensively studied in Merkel cell carcinoma (MCC). We correlated tumoral PD-L1 and IDO1 expression, and intratumoral CD8+ and FoxP3+ lymphocytes count with clinicopathologic variables, Merkel cell polyomavirus (MCPyV) status, and patient outcomes in a series of 132 MCC. By univariate analyses, tumoral PD-L1 expression >1% and combined tumoral PD-L1 >1% and high intratumoral FoxP3+ lymphocyte count correlated with improved overall survival (OS) (p = 0.016, 0.0072), MCC-specific survival (MSS) (p = 0.019, 0.017), and progression-free survival (PFS) (p = 0.043, 0.004, respectively). High intratumoral CD8+ and FoxP3+ lymphocyte count correlated with longer MSS (p = 0.036) and improved PFS (p = 0.047), respectively. Ulceration correlated with worse OS and worse MSS. Age, male gender, and higher stage (3 and 4) significantly correlated with worse survival. MCPyV positivity correlated with immune response. By multivariate analyses, only ulceration and age remained as independent predictors of worse OS;gender and stage remained for shorter PFS. Tumoral PD-L1 expression and increased density of intratumoral CD8+ lymphocytes and FoxP+ lymphocytes may represent favorable prognosticators in a subset of MCCs. Tumoral PD-L1 expression correlated with intratumoral CD8+ and FoxP3+ lymphocytes, which is supportive of an adaptive immune response.

摘要： 2775

关键词： Canada   Glycaemia   Glycaemic control   Hypoglycaemia   Insulin degludec   Real-world   Type 1 diabetes   Type 2 diabetes  

摘要： IntroductionThe aim of the study was to examine glycaemic control and safety of insulin degludec (degludec) in patients with either type 1 diabetes (T1D) or type 2 diabetes (T2D) under routine care settings in *** were extracted from medical records of adults with T1D or T2D who switched to degludec (prandial insulin) from another basal insulin (prandial insulin) >= 6 months prior to data collection. The primary endpoint was change in glycated haemoglobin (HbA(1c)) at 63 months after degludec initiation. Secondary endpoints included change in hypoglycaemia rate in the 6 months before versus the 6 months after switching, and change in mean total daily insulin *** Of 667 patients assessed for eligibility, 626 were included. After 6 +/- 3 months, HbA(1c) decreased from baseline in patients with T1D (- 0.3% [- 0.42, - 0.14](95% CI);p<0.001) and in patients with T2D (- 0.4% [- 0.55, - 0.30](95% CI);p<0.001). In patients with T1D, there were significant reductions in the rates of overall (rate ratio [RR] 0.70), non-severe (RR 0.69), non-severe nocturnal (RR 0.36), and severe nocturnal hypoglycaemia (RR 0.12;all p <= 0.004). In patients with T2D there was a significant reduction in non-severe nocturnal hypoglycaemia (RR 0.22;p<0.001). Mean daily basal insulin dose decreased in patients with T1D (- 1.6 units [- 2.8, - 0.4](95% CI);p=0.008);there was no significant change in patients with T2D (- 0.6 units [- 2.7, 1.4](95% CI);p=0.543).Conclusion In routine clinical practice, improved glycaemic control was observed in patients with T1D or T2D switching to insulin degludec from other basal insulins, with either improvement or no change in hypoglycaemia *** Registration *** NCT03674866

关键词： Colorectal cancer (CRC)   BRAF V600E mutation   yes-activated protein   mitogen-activated protein kinase pathway (MAPK pathway)  

摘要： Background: Most colorectal cancer (CRC) patients with the BRAF V600E mutation display resistance to chemotherapy and targeted medicinal treatments. Thus, exploring new drugs and drug resistance mechanisms for the BRAF V600E mutation has become an urgent clinical priority. Methods: MTS experiment, cell cloning experiment, cell scratching experiment, Transwell experiment, chromatin immunoprecipitation (ChIP), quantitative polymerase chain reaction (qPCR) and flow cytometry are used. Detect the transcription and protein expression of YAP in colorectal cancer cell lines, establish a transient cell line with YAP gene overexpression and knockdown, and detect the effect of YAP gene expression on the biological functions of colorectal cancer cells RKO and HT-29. And further study the mechanism of YAP regulating the response of RAF and MEK targeted therapy. Results: In this study, for the first time, we verified that the expression of transcription factor yes-associated protein (YAP) was upregulated in BRAF V600E mutant CRC cells. After knocking down YAP, we observed a reduction in the growth rate, proliferation, and invasion ability of colon cancer cells. We further verified that YAP knockdown increased sensitivity of BRAF V600E mutant CRC cells to mitogen-activated protein kinase (MAPK) pathway inhibitors. In addition, we clarified the mechanism underlying YAP regulation of RAF and MAPK/extracellular signal- regulated kinase (MEK)-targeted therapy response: YAP cooperates with RAF -> MEK pathway inhibitors to regulate the cell cycle, increase cell G1/S phase arrest, and increase apoptosis. Conclusions: These results suggest that YAP expression may be related to the primary resistance of MAPK inhibitors in metastatic CRC with the BRAF V600E mutation. Therefore, the combination of YAP and MAPK pathway inhibitors in BRAF V600E mutant metastatic CRC may present a promising treatment method.

关键词： composite lymphoma   cutaneous   B-cell lymphoma   T-cell lymphoma  

摘要： Cutaneous lymphomas, both B-cell and T-cell, are not uncommonly seen in the skin, but those lymphomas exhibiting clonality for both B-cell and T-cell populations are scarce. Characterization of dual receptor rearrangement as primary composite lymphoma versus primary lymphoma with reactionary response is complex and often a challenge that goes unrecognized. In this study, we report a unique case of T-cell gene rearrangement positivity complicating the diagnosis of primary cutaneous low-grade B-cell lymphoma along with a review of reported cases containing dual receptor rearrangement to identify trends among final diagnostic decisions. As one might guess, for cutaneous lymphomas presenting with clonality for both T-cell and B-cell receptors, diagnosis can be difficult and confusing because the differential is broad. The literature suggests the majority of these cases may be cutaneous composite lymphomas. However, immunohistochemical, clinical, and histomorphologic features must all be assessed for an accurate diagnosis, which is critical for proper prognosis and therapy.

关键词： Batteries   Energy consumption   Edge computing   Cloud computing   Vehicle dynamics   Optimization   Heuristic algorithms   Fog computing   IoV   SDN   battery life   offloading  

摘要： The Internet of Vehicles (IoV) is one important application scenarios for the development of the Internet of things. The software-defined network (SDN) and fog computing could effectively improve the IoV network dynamics, which enables the application to achieve better performance by offloading some tasks to fog node or cloud center. Current computation offloading approaches for IoV and fog computing mostly focus on resource utilization. However, the energy-aware offloading has not been adequately addressed, especially for IoV systems with many battery-powered roadside units (RSU) and electric vehicles (EV). In this paper, we study the offloading problem in SDN and fog computing-based IoV systems. An energy-aware dynamic offloading scheme is proposed to prolong the running time of the IoV system by leveraging available battery power to execute more applications. The remaining battery power is defined as a dynamic weight factor in the execution cost model to adjust the optimization objective. Meanwhile, the dependence between applications is also taken into consideration in the cost model. A heuristic optimization algorithm is designed to solve the optimization problem. We conducted comprehensive experiments and results have shown that the offloading scheme could execute more applications with the available battery power under the constraints of application dependence.

关键词： cartilage   digital image analysis   live-cell imaging   osteoarthritis   phase-contrast imaging   stem and progenitor cells  

摘要： Reliable and reproducible cell therapy strategies to treat osteoarthritis demand an improved characterization of the cell and heterogeneous cell population resident in native cartilage tissue. Using live-cell phase-contrast time-lapse imaging (PC-TLI), this study investigates the morphological attributes and biological performance of the three primary biological objects enzymatically isolated from primary human cartilage: connective tissue progeni-tors (CTPs), non-progenitors (NPs) and multi-cellular structures (MCSs). The authors' results demonstrated that CTPs were smaller in size in comparison to NPs (P < 0.001). NPs remained part of the adhered cell population throughout the cell culture period. Both NPs and CTP progeny on day 8 increased in size and decreased in circu-larity in comparison to their counterparts on day 1, although the percent change was considerably less in CTP progeny (P < 0.001). PC-TLI analyses indicated three colony types: single-CTP-derived (29%), multiple-CTP-derived (26%) and MCS-derived (45%), with large heterogeneity with respect to cell morphology, proliferation rate and cell density. On average, clonal (CL) (P = 0.009) and MCS (P = 0.001) colonies exhibited higher cell density (cells per colony area) than multi-clonal (MC) colonies;however, it is interesting to note that the behavior of CL (less cells per colony and less colony area) and MCS (high cells per colony and high colony area) colonies was quite different. Overall effective proliferation rate (EPR) of the CTPs that formed CL colonies was higher than the EPR of CTPs that formed MC colonies (P = 0.02), most likely due to CTPs with varying EPR that formed the MC colonies. Finally, the authors demonstrated that lag time before first cell division of a CTP (early attribute) could potentially help predict its proliferation rate long-term. Quantitative morphological characterization using non -invasive PC-TLI serves as a reliable and reproducible technique to understand cell heteroge

摘要： 3125