Although many techniques exist to transfer data from the widely distributed sensors that make up the Internet of Things (IoT) (e.g., using 3G/4G networks or cables), these methods are associated with ...prohibitively high costs, making them impractical for real-life applications. Recently, several emerging wireless technologies have been proposed to provide long-range communication for IoT sensors. Among these, LoRa has been examined for long-range performance. Although LoRa shows good performance for long-range transmission in the countryside, its radio signals can be attenuated over distance, and buildings, trees, and other radio signal sources may interfere with the signals. Our observations show that in urban areas, LoRa requires dense deployment of LoRa gateways (GWs) to ensure that indoor LoRa devices can successfully transfer data back to remote GWs. Wireless mesh networking is a solution for increasing communication range and packet delivery ratio (PDR) without the need to install additional GWs. This paper presents a LoRa mesh networking system for large-area monitoring of IoT applications. We deployed 19 LoRa mesh networking devices over an <inline-formula> <tex-math notation="LaTeX">800\,\,\text {m} \times 600 </tex-math></inline-formula> m area on our university campus and installed a GW that collected data at 1-min intervals. The proposed LoRa mesh networking system achieved an average 88.49% PDR, whereas the star-network topology used by LoRa achieved only 58.7% under the same settings. To the best of our knowledge, this is the first academic study discussing LoRa mesh networking in detail and evaluating its performance via real experiments.
Immune checkpoint inhibitors (ICIs) with nivolumab and pembrolizumab are promising agents for advanced hepatocellular carcinoma (HCC) but lack of effective biomarkers. We aimed to investigate the ...potential predictors of response and factors associated with overall survival (OS) for ICI treatment in unresectable HCC patients. Ninety-five patients who received nivolumab or pembrolizumab for unresectable HCC were enrolled for analyses. Radiologic evaluation was based on RECIST v1.1. Factors associated with outcomes were analyzed. Of 90 patients with evaluable images, the objective response rate (ORR) was 24.4%. Patients at Child-Pugh A or received combination treatment had higher ORR. Early alpha-fetoprotein (AFP) >10% reduction (within 4 weeks) was the only independent predictor of best objective response (odds ratio: 7.259,
= 0.001). For patients with baseline AFP ≥10 ng/mL, significantly higher ORR (63.6% vs. 10.2%,
< 0.001) and disease control rate (81.8% vs. 14.3%,
< 0.001) were observed in those with early AFP reduction than those without. In addition, early AFP reduction and albumin-bilirubin (ALBI) grade or Child-Pugh class were independent factors associated with OS in different models. In conclusion, a 10-10 rule of early AFP response can predict objective response and survival to ICI treatment in unresectable HCC. ALBI grade and Child-Pugh class determines survival by ICI treatment.
Displays based on inorganic light-emitting diodes (LED) are considered as the most promising one among the display technologies for the next-generation. The chip for LED display bears similar ...features to those currently in use for general lighting, but it size is shrunk to below 200 microns. Thus, the advantages of high efficiency and long life span of conventional LED chips are inherited by miniaturized ones. As the size gets smaller, the resolution enhances, but at the expense of elevating the complexity of fabrication. In this review, we introduce two sorts of inorganic LED displays, namely relatively large and small varieties. The mini-LEDs with chip sizes ranging from 100 to 200 μm have already been commercialized for backlight sources in consumer electronics applications. The realized local diming can greatly improve the contrast ratio at relatively low energy consumptions. The micro-LEDs with chip size less than 100 μm, still remain in the laboratory. The full-color solution, one of the key technologies along with its three main components, red, green, and blue chips, as well color conversion, and optical lens synthesis, are introduced in detail. Moreover, this review provides an account for contemporary technologies as well as a clear view of inorganic and miniaturized LED displays for the display community.
The brain predominantly expressed RING finger protein, Znf179, is known to be important for embryonic neuronal differentiation during brain development. Downregulation of Znf179 has been observed in ...motor neurons of adult mouse models for amyotrophic lateral sclerosis (ALS), yet the molecular function of Znf179 in neurodegeneration has never been previously described. Znf179 contains the classical C3HC4 RING finger domain, and numerous proteins containing C3HC4 RING finger domain act as E3 ubiquitin ligases. Hence, we are interested to identify whether Znf179 possesses E3 ligase activity and its role in ALS neuropathy.
We used in vivo and in vitro ubiquitination assay to examine the E3 ligase autoubiquitination activity of Znf179 and its effect on 26S proteasome activity. To search for the candidate substrates of Znf179, we immunoprecipitated Znf179 and subjected to mass spectrometry (MS) analysis to identify its interacting proteins. We found that ALS/ FTLD-U (frontotemporal lobar degeneration (FTLD) with ubiquitin inclusions)-related neurodegenerative TDP-43 protein is the E3 ligase substrate of Znf179. To further clarify the role of E3 ubiquitin ligase Znf179 in neurodegenerative TDP-43-UBI (ubiquitinated inclusions) (+) proteinopathy, the effect of Znf179-mediated TDP-43 polyubiquitination on TDP-43 protein stability, aggregate formation and nucleus/cytoplasm mislocalization were evaluated in vitro cell culture system and in vivo animal model.
Here we report that Znf179 is a RING E3 ubiquitin ligase which possesses autoubiquitination feature and regulates 26S proteasome activity through modulating the protein expression levels of 19S/20S proteasome subunits. Our immunoprecipitation assay and MS analysis results revealed that the neuropathological TDP-43 protein is one of its E3 ligase substrate. Znf179 interactes with TDP-43 protein and mediates polyubiquitination of TDP-43 in vitro and in vivo. In neurodegenerative TDP-43 proteinopathy, we found that Znf179-mediated polyubiquitination of TDP-43 accelerates its protein turnover rate and attenuates insoluble pathologic TDP-43 aggregates, while knockout of Znf179 in mouse brain results in accumulation of insoluble TDP-43 and cytosolic TDP-43 inclusions in cortex, hippocampus and midbrain regions.
Here we unveil the important role for the novel E3 ligase Znf179 in TDP-43-mediated neuropathy, and provide a potential therapeutic strategy for combating ALS/ FTLD-U neurodegenerative pathologies.
•An isolated microalga N. oceanica CY2 exhibits high potential of producing EPA.•Light intensity and nitrogen source concentration were optimized for EPA production.•EPA production of N. oceanica CY2 ...was improved when using LED-blue illumination.•Combining semi-batch operation and LED PBR resulted in excellent EPA production.
Microalgae have emerged as promising resources for highly unsaturated fatty acids. In this study, an indigenous microalga identified as Nannochloropsis oceanica CY2 was grown photoautotrophically to produce eicosapentaenoic acid (EPA; 20:5, n-3). Specific engineering strategies were employed to stimulate EPA accumulation in the microalgal cells. The results show that BG-11 was the most effective medium to grow N. oceanica CY2, giving an EPA content and biomass concentration of 2.38% (per dry cell weight) and 1.53g/l. The EPA content nearly doubled when using the optimal nitrogen source (NaNO3) at a concentration of 1.50g/l. The illumination system also markedly affected the EPA content for the photoautotrophic microalga. When the microalgal culture was illuminated with a red LED, an impressively high EPA content of 5.5% was obtained. Finally, using semi-batch cultures operations with LED-blue illumination, the EPA content of N. oceanica CY2 was stably maintained at 5.0%.
Aim
To analyse large‐scale cardiovascular outcome trials of sodium‐glucose co‐transporter‐2 (SGLT‐2) inhibitors to evaluate whether there are safety concerns with respect to major adverse limb events ...overall or among various high‐risk subgroups of patients.
Methods
We performed a quantitative meta‐analysis of randomized, placebo‐controlled, cardiovascular outcome trials of SGLT‐2 inhibitors in patients with type 2 diabetes. We searched the PubMed, Embase and Cochrane databases for trials published up until 30 June 2020. The efficacy outcomes analysed included amputations and were stratified by several subgroup variables, including age, duration of diabetes, glucose control, renal function, established peripheral artery disease and diabetes microvascular complications. This review was registered before completing the analysis.
Results
Among 383 records identified, six studies assessing the following three SGLT‐2 inhibitors met our inclusion criteria: empagliflozin (EMPA‐REG OUTCOME study), canagliflozin (CANVAS Program and CREDENCE study), dapagliflozin (DECLARE‐TIMI 58 and DAPA‐HF trials) and ertugliflozin (VERTIS CV study). Of a total of 51 713 participants, 858 required amputation operations. The event rates of amputation were 2.0% (535/26 778) and 1.3% (323/24 927) in the SGLT‐2 inhibitor and control groups, respectively. The random effects model revealed that SGLT‐2 inhibitors were not significantly associated with an increased risk of amputation with substantial heterogeneity (pooled risk ratio, 1.24; 95% confidence interval, 0.96 to 1.60; I2 = 67.5%). This neutral effect of SGLT‐2 inhibitors was also consistent across different levels of subgroups, including subgroups with or without established peripheral artery disease (PAD).
Conclusions
SGLT‐2 inhibitors are not associated with increased risks of amputation operations even among various high‐risk subgroups, including patients with PAD. The amputation events primarily arise from critical limb ischaemia and infection instead of acute limb ischaemia. A multi‐centre study focused on major adverse limb events with a longer follow‐up is needed to confirm these results and provide guidelines for clinical practice.
Background & Aims Mother-to-infant transmission is the major cause of hepatitis B virus (HBV) infection among immunized children. There has been much debate about screening pregnant women and ...administering hepatitis B immunoglobulin (HBIG) to newborns. We analyzed the rate of HBV infection among children born to hepatitis B surface antigen (HBsAg)-positive mothers and whether HBIG administration reduces transmission. Methods We analyzed data from 2356 children born to HBsAg-positive mothers, identified through prenatal maternal screens. In addition to HBV vaccines, HBIG was given to all 583 children with hepatitis B e antigen (HBeAg)-positive mothers and to 723 of 1773 children with HBeAg-negative mothers. Serology tests for HBV were performed from 2007 to 2009, when children were 0.5–10 years old. Results A significantly greater percentage of children with HBeAg-positive mothers tested positive for antibodies against the hepatitis B core protein (16.76%) and HBsAg (9.26%) than children with HBeAg-negative mothers (1.58% and 0.29%, respectively; P < .0001 and <.001). Among the HBV-infected children, the rate of chronicity also was higher among children with HBeAg-positive mothers than children with HBeAg-negative mothers (54% vs 17%; P = .002). Similar rates of antibodies against the hepatitis B core protein (0.99% and 1.88%; P = .19) and HBsAg (0.14% and 0.29%; P = .65) were noted in children born to HBeAg-negative mothers who were or were not given HBIG. Infantile fulminant hepatitis developed in 1 of 1050 children who did not receive HBIG (.095%). Conclusions Children born to HBeAg-positive mothers are at greatest risk for chronic HBV infection (9.26%), despite immunization. Administration of HBIG to infants born to HBeAg-negative mothers did not appear to reduce the rate of chronic HBV infection, but might prevent infantile fulminant hepatitis. Screening pregnant women for HBsAg and HBeAg might control mother-to-infant transmission of HBV.
Vascular endothelial growth factor (VEGF) plays a role in the tumor microenvironment. Sorafenib, which inhibits the VEGF pathway, has an immune-modulation function but lacks substantial clinical ...data. This study aims to explore the efficacy of anti-PD-1 combined sorafenib in advanced hepatocellular carcinoma (HCC).
HCC patients who underwent anti-PD-1 treatment at Taipei Veterans General Hospital (Taipei, Taiwan) between January 2016 and February 2019 were reviewed. The efficacy was compared between groups after propensity-score matching.
There were 173 HCC patients receiving anti-PD-1. After excluding unsuitable cases, 140 patients were analyzed, of which 58 received combination therapy and 82 received anti-PD-1 alone. The combination therapy had a trend of higher CR rate (8.6% vs. 4.9%, ns.), ORR (22.4% vs. 19.5%, ns.) and significantly higher DCR (69.0% vs. 37.8%, p < 0.05) comparing to anti-PD-1 alone. After matching, combination group achieved longer progression-free survival (3.87 vs. 2.43 months, p < 0.05) and overall survival (not reached vs. 7.17 months, p < 0.05) than anti-PD-1 alone, without higher grade 3/4 AE (10.3% vs. 7.1%, p = 0.73). The tumor response varied among different metastatic sites, with high responses in adrenal glands, peritoneum and lungs. The more AFP declined (> 10, > 50 and > 66%), the higher the ORR (70, 80 and 92%) and CR rates (30, 35 and 58%) were achieved at day 28.
This is the first study to demonstrate the combination of anti-PD-1 and sorafenib had better efficacy and survival benefit. A prospective randomized study is needed to confirm this finding.
Kidney transplant patients require life-long surveillance to detect allograft rejection. Repeated biopsy, albeit the clinical gold standard, is an invasive procedure with the risk of complications ...and comparatively high cost. Conversely, serum creatinine or urinary proteins are noninvasive alternatives but are late markers with low specificity. We report a urine-based platform to detect kidney transplant rejection. Termed iKEA (integrated kidney exosome analysis), the approach detects extracellular vesicles (EVs) released by immune cells into urine; we reasoned that T cells, attacking kidney allografts, would shed EVs, which in turn can be used as a surrogate marker for inflammation. We optimized iKEA to detect T-cell-derived EVs and implemented a portable sensing system. When applied to clinical urine samples, iKEA revealed high level of CD3-positive EVs in kidney rejection patients and achieved high detection accuracy (91.1%). Fast, noninvasive, and cost-effective, iKEA could offer new opportunities in managing transplant recipients, perhaps even in a home setting.
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