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Impact of Wearing Masks, Hand Hygiene, and Social Distancing on Influenza, Enterovirus, and All-Cause Pneumonia During the Coronavirus Pandemic: Retrospective National Epidemiological Surveillance Study
The coronavirus disease (COVID-19) pandemic is an important health crisis worldwide. Several strategies were implemented to combat COVID-19, including wearing masks, hand hygiene, and social distancing. The impact of these strategies on COVID-19 and other viral infections remains largely unclear.
We aim to investigate the impact of implemented infectious control strategies on the incidences of influenza, enterovirus infection, and all-cause pneumonia during the COVID-19 pandemic.
We utilized the electronic database of the Taiwan National Infectious Disease Statistics System and extracted incidences of COVID-19, influenza virus, enterovirus, and all-cause pneumonia. We compared the incidences of these diseases from week 45 of 2016 to week 21 of 2020 and performed linear regression analyses.
The first case of COVID-19 in Taiwan was reported in late January 2020 (week 4). Infectious control strategies have been promoted since late January. The influenza virus usually peaks in winter and decreases around week 14. However, a significant decrease in influenza was observed after week 6 of 2020. Regression analyses produced the following results: 2017, R
=0.037; 2018, R
=0.021; 2019, R
=0.046; and 2020, R
=0.599. A dramatic decrease in all-cause pneumonia was also reported (R
values for 2017-2020 were 0.435, 0.098, 0.352, and 0.82, respectively). Enterovirus had increased by week 18 in 2017-2019, but this was not observed in 2020.
Using this national epidemiological database, we found a significant decrease in cases of influenza, enterovirus, and all-cause pneumonia during the COVID-19 pandemic. Wearing masks, hand hygiene, and social distancing may contribute not only to the prevention of COVID-19 but also to the decline of other respiratory infectious diseases. Further studies are warranted to elucidate the causal relationship.
Journal Article
Green and software-defined wireless networks : from theory to practice
\"Understand the fundamental theory and practical design aspects of green and soft wireless communications networks with this expert text. It provides comprehensive and unified coverage of 5G physical layer design, as well as design of the higher and radio access layers and the core network, drawing on viewpoints from both academia and industry. Get to grips with the theory through authoritative discussion of information-theoretical results, and learn about fundamental green design trade-offs, software-defined network architectures, and energy-efficient radio resource management strategies. Applications of wireless big data and artificial intelligence to wireless network design are included, providing an excellent design reference, and real-world examples of employment in software-defined 5G networks and energy-saving solutions from wireless communications companies and cellular operators help to connect theory with practice. This is an essential text for graduate students, professionals and researchers\"-- Provided by publisher.
Book
BiTE‐Secreting CAR‐γδT as a Dual Targeting Strategy for the Treatment of Solid Tumors
HLA‐G is considered as an immune checkpoint protein and a tumor‐associated antigen. In the previous work, it is reported that CAR‐NK targeting of HLA‐G can be used to treat certain solid tumors. However, the frequent co‐expression of PD‐L1 and HLA‐G) and up‐regulation of PD‐L1 after adoptive immunotherapy may decrease the effectiveness of HLA‐G‐CAR. Therefore, simultaneous targeting of HLA‐G and PD‐L1 by multi‐specific CAR could represent an appropriate solution. Furthermore, gamma‐delta T (γδT) cells exhibit MHC‐independent cytotoxicity against tumor cells and possess allogeneic potential. The utilization of nanobodies offers flexibility for CAR engineering and the ability to recognize novel epitopes. In this study, Vδ2 γδT cells are used as effector cells and electroporated with an mRNA‐driven, nanobody‐based HLA‐G‐CAR with a secreted PD‐L1/CD3ε Bispecific T‐cell engager (BiTE) construct (Nb‐CAR.BiTE). Both in vivo and in vitro experiments reveal that the Nb‐CAR.BiTE‐γδT cells could effectively eliminate PD‐L1 and/or HLA‐G‐positive solid tumors. The secreted PD‐L1/CD3ε Nb‐BiTE can not only redirect Nb‐CAR‐γδT but also recruit un‐transduced bystander T cells against tumor cells expressing PD‐L1, thereby enhancing the activity of Nb‐CAR‐γδT therapy. Furthermore, evidence is provided that Nb‐CAR.BiTE redirectes γδT into tumor‐implanted tissues and that the secreted Nb‐BiTE is restricted to the tumor site without apparent toxicity.
Elevated PD‐L1 in solid tumors increases the risk of immune escape from HLA‐G‐CAR cell therapy. The bicistronic mRNA construct that drives PD‐L1 Nb‐BiTE and HLA‐G Nb‐CAR in γδT cells via electroporation is designed to address this issue. This Nb‐CAR.BiTE‐γδT therapy can overcome HLA‐G and PD‐L1 dilemma and even kill tumor cells with inadequate antigen expression, resulting in potent anti‐tumor activity without apparent toxicity.
Journal Article
Update in the epidemiology, risk factors, screening, and treatment of diabetic retinopathy
Despite progress in the treatment of diabetic macular edema and diabetic retinopathy, the rate of lower fundus examination due to limitations of medical resources delays the diagnosis and treatment of diabetic retinopathy. Therefore, implementation of automated diabetic retinopathy screening program and the identification of more specific and sensitive biomarkers are important for facilitating the earlier detection of diabetic macular edema and diabetic retinopathy to decrease the prevalence of poor vision and blindness.
Journal Article
Helical structure motifs made searchable for functional peptide design
The systematic design of functional peptides has technological and therapeutic applications. However, there is a need for pattern-based search engines that help locate desired functional motifs in primary sequences regardless of their evolutionary conservation. Existing databases such as The Protein Secondary Structure database (PSS) no longer serves the community, while the Dictionary of Protein Secondary Structure (DSSP) annotates the secondary structures when tertiary structures of proteins are provided. Here, we extract 1.7 million helices from the PDB and compile them into a database (Therapeutic Peptide Design database; TP-DB) that allows queries of compounded patterns to facilitate the identification of sequence motifs of helical structures. We show how TP-DB helps us identify a known purification-tag-specific antibody that can be repurposed into a diagnostic kit for
Helicobacter pylori
. We also show how the database can be used to design a new antimicrobial peptide that shows better
Candida albicans
clearance and lower hemolysis than its template homologs. Finally, we demonstrate how TP-DB can suggest point mutations in helical peptide blockers to prevent a targeted tumorigenic protein-protein interaction. TP-DB is made available at
http://dyn.life.nthu.edu.tw/design/
.
Here, we present TP-DB; a pattern-based search engine based on 1.67 million helices from the Protein Database (PDB). We demonstrate the utility of TP-DB in identifying microbe-specific antigens, as well as the design of antimicrobial peptides and Protein-protein interaction blockers.
Journal Article
Adjuvant treatments for resected pancreatic adenocarcinoma: a systematic review and network meta-analysis
Major adjuvant treatments for pancreatic adenocarcinoma include fluorouracil, gemcitabine, chemoradiation, and chemoradiation plus fluorouracil or gemcitabine. Since the optimum regimen remains inconclusive, we aimed to compare these treatments in terms of overall survival after tumour resection and in terms of grade 3–4 toxic effects with a systematic review and random-effects Bayesian network meta-analysis.
We searched PubMed, trial registries, and related reviews and abstracts for randomised controlled trials comparing the above five treatments with each other or observation alone before April 30, 2013. We estimated relative hazard ratios (HRs) for death and relative odds ratios (ORs) for toxic effects among different therapies by combining HRs for death and survival durations and ORs for toxic effects of included trials. We assessed the effects of prognostic factors on survival benefits of adjuvant therapies with meta-regression.
Ten eligible articles reporting nine trials were included. Compared with observation, the HRs for death were 0·62 (95% credible interval 0·42–0·88) for fluorouracil, 0·68 (0·44–1·07) for gemcitabine, 0·91 (0·55–1·46) for chemoradiation, 0·54 (0·15–1·80) for chemoradiation plus fluorouracil, and 0·44 (0·10–1·81) for chemoradiation plus gemcitabine. The proportion of patients with positive lymph nodes was inversely associated with the survival benefit of adjuvant treatments. After adjustment for this factor, fluorouracil (HR 0·65, 0·49–0·84) and gemcitabine (0·59, 0·41–0·83) improved survival compared with observation, whereas chemoradiation resulted in worse survival than fluorouracil (1·69, 1·12–2·54) or gemcitabine (1·86, 1·04–3·23). Chemoradiation plus gemcitabine was ranked the most toxic, with significantly higher haematological toxic effects than second-ranked chemoradiation plus fluorouracil (OR 13·33, 1·01–169·36).
Chemotherapy with fluorouracil or gemcitabine is the optimum adjuvant treatment for pancreatic adenocarcinoma and reduces mortality after surgery by about a third. Chemoradiation plus chemotherapy is less effective in prolonging survival and is more toxic than chemotherapy.
None.
Journal Article
Association Among Serum Perfluoroalkyl Chemicals, Glucose Homeostasis, and Metabolic Syndrome in Adolescents and Adults
OBJECTIVE: Perfluoroalkyl chemicals (PFCs) have been used worldwide in a variety of consumer products. The effect of PFCs on glucose homeostasis is not known. RESEARCH DESIGN AND METHODS: We examined 474 adolescents and 969 adults with reliable serum measures of metabolic syndrome profile from the National Health and Nutrition Examination Survey 1999-2000 and 2003-2004. RESULTS: In adolescents, increased serum perfluorononanoic acid (PFNA) concentrations were associated with hyperglycemia (odds ratio [OR] 3.16 [95% CI 1.39-7.16], P < 0.05). Increased serum PFNA concentrations also have favorable associations with serum HDL cholesterol (0.67 [0.45-0.99], P < 0.05). Overall, increased serum PFNA concentrations were inversely correlated with the prevalence of the metabolic syndrome (0.37 [0.21-0.64], P < 0.005). In adults, increased serum perfluorooctanoic acid concentrations were significantly associated with increased β-cell function (β coefficient 0.07 ± 0.03, P < 0.05). Increased serum perfluorooctane sulfate (PFOS) concentrations were associated with increased blood insulin (0.14 ± 0.05, P < 0.01), homeostasis model assessment of insulin resistance (0.14 ± 0.05, P < 0.01), and β-cell function (0.15 ± 0.05, P < 0.01). Serum PFOS concentrations were also unfavorably correlated with serum HDL cholesterol (OR 1.61 [95% CI 1.15-2.26], P < 0.05). CONCLUSIONS: Serum PFCs were associated with glucose homeostasis and indicators of metabolic syndrome. Further clinical and animal studies are warranted to clarify putative causal relationships.
Journal Article
GRK6 palmitoylation dictates triple-negative breast cancer metastasis via recruiting the β-Arrestin 2/MAPKs/NF-κB signaling axis
Background
Triple negative breast cancer (TNBC) belongs to the worst prognosis of breast cancer subtype probably because of distant metastasis to other organs, e.g. lungs. However, the mechanism underlying TNBC metastasis remains largely unknown.
Methods
Bioinformatics analysis was conducted to evaluate the mRNA/protein expression and prognostic significance of G protein–coupled receptor kinase 6 (GRK6) in BC subtypes. RT-PCR assays were used to test the GRK6 expression in human BC tissues and cell lines. The in vitro cellular migration and in vivo lung colony-forming assays were established to estimate the metastatic potentials of TNBC cells. Western blotting was employed to examine protein phosphorylation, translocation and expression in the designed experiments.
Results
Here we show that GRK6 upregulation is extensively detected in TNBC compared to normal mammary tissues and other BC subtypes and correlates with an increased risk for distant metastasis in TNBC patients. GRK6 knockdown suppressed but overexpression potentiated the cellular migration and lung colony-forming abilities of TNBC cells. Moreover, our data demonstrated that the posttranslational palmitoylation of GRK6 is extremely critical for activating β-Arrestin 2/mitogen-activated protein kinases (MAPKs)/NF-κB signaling axis and fostering the metastatic potentials of TNBC cells. Accordingly, the pharmaceutical inhibition of GRK6 kinase activity dramatically suppressed the activation of β-Arrestin 2, MAPKs and NF-κB and the cellular migration ability of highly metastatic MDA-MB231 cells. Sequentially blocking the β-Arrestin 2/MAPKs/NF-κB axis with their inhibitors predominantly mitigated the GRK6-promoted migration ability of poorly metastatic HCC1937 cells.
Conclusion
Our results not only provide a novel mechanism for TNBC metastasis but also offer a new therapeutic strategy to combat metastatic TNBC via targeting GRK6 activity.
Journal Article