The sudden outbreak of 2019 novel coronavirus (2019-nCoV, later named SARS-CoV-2) in Wuhan, China, which rapidly grew into a global pandemic, marked the third introduction of a virulent coronavirus ...into the human society, affecting not only the healthcare system, but also the global economy. Although our understanding of coronaviruses has undergone a huge leap after two precedents, the effective approaches to treatment and epidemiological control are still lacking. In this article, we present a succinct overview of the epidemiology, clinical features, and molecular characteristics of SARS-CoV-2. We summarize the current epidemiological and clinical data from the initial Wuhan studies, and emphasize several features of SARS-CoV-2, which differentiate it from SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), such as high variability of disease presentation. We systematize the current clinical trials that have been rapidly initiated after the outbreak of COVID-19 pandemic. Whereas the trials on SARS-CoV-2 genome-based specific vaccines and therapeutic antibodies are currently being tested, this solution is more long-term, as they require thorough testing of their safety. On the other hand, the repurposing of the existing therapeutic agents previously designed for other virus infections and pathologies happens to be the only practical approach as a rapid response measure to the emergent pandemic, as most of these agents have already been tested for their safety. These agents can be divided into two broad categories, those that can directly target the virus replication cycle, and those based on immunotherapy approaches either aimed to boost innate antiviral immune responses or alleviate damage induced by dysregulated inflammatory responses. The initial clinical studies revealed the promising therapeutic potential of several of such drugs, including
, a broad-spectrum antiviral drug that interferes with the viral replication, and
, the repurposed antimalarial drug that interferes with the virus endosomal entry pathway. We speculate that the current pandemic emergency will be a trigger for more systematic drug repurposing design approaches based on big data analysis.
Emerging evidence suggests that gut microbiome composition alterations affect neurodegeneration through neuroinflammation in the pathogenesis of Parkinson's disease (PD). Here, we evaluate gut ...microbiota alterations and host cytokine responses in a population of Taiwanese patients with PD.
Fecal microbiota communities from 80 patients with PD and 77 age and gender-matched controls were assessed by sequencing the V3-V4 region of the 16S ribosomal RNA gene. Diet and comorbidities were controlled in the analyses. Plasma concentrations of IL-1β, IL-2, IL-4, IL-6, IL-13, IL-18, GM-CSF, IFNγ, and TNFα were measured by a multiplex immunoassay and relationships between microbiota, clinical characteristics, and cytokine levels were analyzed in the PD group. We further examined the cytokine changes associated with the altered gut microbiota seen in patients with PD in another independent cohort of 120 PD patients and 120 controls.
Microbiota from patients with PD was altered relative to controls and dominated by Verrucomicrobia, Mucispirillum, Porphyromonas, Lactobacillus, and Parabacteroides. In contrast, Prevotella was more abundant in controls. The abundances of Bacteroides were more increased in patients with non-tremor PD subtype than patients with tremor subtype. Bacteroides abundance was correlated with motor symptom severity defined by UPDRS part III motor scores (rho = 0.637 95% confidence interval 0.474 to 0.758, P < 0.01). Altered microbiota was correlated with plasma concentrations of IFNγ and TNFα. There was a correlation between Bacteroides and plasma level of TNFα (rho = 0.638 95% CI: 0.102-0.887, P = 0.02); and a correlation between Verrucomicrobia abundance and plasma concentrations of IFNγ (rho = 0.545 95% CI - 0.043-0.852, P = 0.05). The elevated plasma cytokine responses were confirmed in an additional independent 120 patients with PD and 120 controls (TNFα: PD vs. control 8.51 ± 4.63 pg/ml vs. 4.82 ± 2.23 pg/ml, P < 0.01; and IFNγ: PD vs. control: 38.45 ± 7.12 pg/ml vs. 32.79 ± 8.03 pg/ml, P = 0.03).
This study reveals altered gut microbiota in PD and its correlation with clinical phenotypes and severity in our population. The altered plasma cytokine profiles associated with gut microbiome composition alterations suggest aberrant immune responses may contribute to inflammatory processes in PD.
HCV prevails in uremic haemodialysis patients. The current study aimed to achieve HCV microelimination in haemodialysis centres through a comprehensive outreach programme.
The ERASE-C Campaign is an ...outreach programme for the screening, diagnosis and group treatment of HCV encompassing 2323 uremic patients and 353 medical staff members from 18 haemodialysis centres. HCV-viremic subjects were linked to care for directly acting antiviral therapy or received on-site sofosbuvir/velpatasvir therapy. The objectives were HCV microelimination (>80% reduction of the HCV-viremic rate 24 weeks after the end of the campaign in centres with ≥90% of the HCV-viremic patients treated) and 'No-C HD' (no HCV-viremic subjects at the end of follow-up).
At the preinterventional screening, 178 (7.7%) uremic patients and 2 (0.6%) staff members were HCV-viremic. Among them, 146 (83.9%) uremic patients received anti-HCV therapy (41 link-to-care; 105 on-site sofosbuvir/velpatasvir). The rates of sustained virological response (SVR12, undetectable HCV RNA 12 weeks after the end of treatment) in the full analysis set and per-protocol population were 89.5% (94/105) and 100% (86/86), respectively, in the on-site treatment group, which were comparable with the rates of 92.7% (38/41) and 100% (38/38), respectively, in the link-to-care group. Eventually, the HCV-viremic rate decreased to 0.9% (18/1,953), yielding an 88.3% reduction from baseline. HCV microelimination and 'No-C HD' were achieved in 92.3% (12/13) and 38.9% (7/18) of the haemodialysis centres, respectively.
Outreach strategies with mass screenings and on-site group treatment greatly facilitated HCV microelimination in the haemodialysis population.
NCT03803410 and NCT03891550.
High dosage and longer duration of antiviral treatment has been suggested to treat cryoglobulinemia patients. We aimed to investigate the efficacy of antiviral treatment in cryoglobulinemia patients ...and analyze the associated factors of persistent cryoglobulinemia.
Totally 148 patients after completion of anti-HCV treatment were enrolled in our study. Serum cryoglobulinemia precipitation was assessed and analyzed for the associated factors after antiviral therapy.
Fifty-one (34.5%) out of 148 patients were positive for serum cryoglobulinemia after completion of antiviral therapy. In multivariate analysis, advanced fibrosis (Odds Ratio OR- 4.13, 95% Confidence Interval 95% CI- 1.53-11.17, p = 0.005) and platelet counts (OR-0.98, 95% CI- 0.97-0.99, p = 0.010) were independently and significantly associated with persistent cryoglobulinemia. The factors associated with the persistent cryoglobulinemia in SVR patients were advanced fibrosis (OR-1.93, 95% CI- 1.02-3.65, p = 0.041) and platelet count (OR-0.98, 95% CI- 0.96-0.99, p = 0.041) by multivariate analysis. Multivariate logistic regression analysis showed persistent (OR-4.83, 95% CI- 1.75-13.36, p = 0.002) was significantly associated with advanced fibrosis in patients with cryoglobulinemia follow up after antiviral therapy.
The prevalence of the persistent cryoglobulinemia is 34.5% after completing antiviral therapy and it is associated with advanced fibrosis, also HCV clearance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Oxaliplatin (OXA), is a third generation platinum drug used as first‐line chemotherapy in colorectal cancer (CRC). Cancer cells acquires resistance to anti‐cancer drug and develops resistance. ...ATP‐binding cassette (ABC) drug transporter ABCG2, one of multidrug resistance (MDR) protein which can effectively discharge a wide spectrum of chemotherapeutic agents out of cancer cells and subsequently reduce the intracellular concentration of these drugs. Role of ABCG2 and plausible molecular signaling pathways involved in Oxaliplatin‐Resistant (OXA‐R) colon cancer cells was evaluated in the present study. OXA resistant LoVo cells was developed by exposing the colon cells to OXA in a dose‐dependent manner. Development of multi drug resistance in OXA‐R cells was confirmed by exposing the resistance cells to oxaliplatin, 5‐FU, and doxorubicin. OXA treatment resulted in G2 phase arrest in parental LoVo cells, which was overcome by OXA‐R LoVo cells. mRNA and protein expression of ABCG2 and phosphorylation of NF‐κB was significantly higher in OXA‐R than parental cells. Levels of ER stress markers were downregulated in OXA‐R than parental cells. OXA‐R LoVo cells exposed to NF‐κB inhibitor QNZ effectively reduced the ABCG2 and p‐NF‐κB expression and increased ER stress marker expression. On other hand, invasion and migratory effect of OXA‐R cells were found to be decreased, when compared to parental cells. Metastasis marker proteins also downregulated in OXA‐R cells. ABCG2 inhibitor verapamil, downregulate ABCG2, induce ER stress markers and induces apoptosis. In vivo studies in nude mice also confirms the same.
Present study was designed to evaluate plausible role of ABCG2, multi drug resistance protein and associated pathway involved in OXA‐R LoVo cells. Our data show that oxaliplatin resistant LoVo colon cells are resistant to oxaliplatin, 5‐FU, and doxorubicin. Multi drug resistance acquired by overexpression of ABCG2 and p‐NF‐κB and downregulation of ER stress protein thereby preventing apoptosis.
Long-distance entanglement distribution is essential for both foundational tests of quantum physics and scalable quantum networks. Owing to channel loss, however, the previously achieved distance was ...limited to ~100 kilometers. Here we demonstrate satellite-based distribution of entangled photon pairs to two locations separated by 1203 kilometers on Earth, through two satellite-to-ground downlinks with a summed length varying from 1600 to 2400 kilometers. We observed a survival of two-photon entanglement and a violation of Bell inequality by 2.37 ± 0.09 under strict Einstein locality conditions. The obtained effective link efficiency is orders of magnitude higher than that of the direct bidirectional transmission of the two photons through telecommunication fibers.
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•A herb-based formula delivers positive clinical outcomes on COVID-19 patients.•The formula inhibits SARS-CoV-2 pathogenesis in anti-viral & -inflammatory assays.•Real-world-evidence ...offers insights to inform drug development.•Bed-to-bench approach shortens the time required for finding effective therapeutics.
COVID-19 is a global pandemic, with over 50 million confirmed cases and 1.2 million deaths as of November 11, 2020. No therapies or vaccines so far are recommended to treat or prevent the new coronavirus. A novel traditional Chinese medicine formula, Taiwan Chingguan Yihau (NRICM101), has been administered to patients with COVID-19 in Taiwan since April 2020. Its clinical outcomes and pharmacology have been evaluated. Among 33 patients with confirmed COVID-19 admitted in two medical centers, those (n = 12) who were older, sicker, with more co-existing conditions and showing no improvement after 21 days of hospitalization were given NRICM101. They achieved 3 consecutive negative results within a median of 9 days and reported no adverse events. Pharmacological assays demonstrated the effects of the formula in inhibiting the spike protein/ACE2 interaction, 3CL protease activity, viral plaque formation, and production of cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α. This bedside-to-bench study suggests that NRICM101 may disrupt disease progression through its antiviral and anti-inflammatory properties, offering promise as a multi-target agent for the prevention and treatment of COVID-19.
An Internet of Things gateway serves as a key intermediary between numerous smart things and their corresponding cloud networking servers. A typical conventional gateway system uses a high-level ...embedded microcontroller (MCU) as its core; that MCU performs low-level perception-layer device network management, upper-level cloud server functions, and remote mobile computation services. However, in edge computing, many factors need to be considered when designing an IoT gateway, such as minimizing the response time, the power consumption, and the bandwidth cost. Regarding system scalability, computational efficiency, and communication efficiency, solutions that use a single MCU cannot deliver IoT functionality such as big data collection, management, real-time communication, expandable peripherals, and various other services. Therefore, this article proposes an innovative multi-MCU system framework combining a field-programmable- gate-array-based hardware bridge and multiple scalable MCUs to realize an edge gateway of a smart sensor fieldbus network. Through distributed and collaborative computing, the multi-MCU edge gateway can efficiently perform fieldbus network management, embedded data collection, and networking communication, thereby considerably reducing the real-time power consumption and improving scalability compared to the existing industrial IoT solutions.
This study utilizes the mold flow analysis technique of the injection compression molding (ICM) process, combined with the Taguchi–gray relational analysis (GRA), for process optimization analysis on ...the roundness of the lens holes and the flatness of the lens mount in a 4 × 4 planar multilens array mount. After manufacturing simulation analysis, the eccentricity and tilt information of the lens mount was further evaluated optically through spot diagram analysis upon inserting the same glass lenses. The results showed a positive correlation trend between roundness and flatness in structural deformation analysis, indicating that improving the overall flatness of the lens mount can enhance the roundness of the lens holes. In optical analysis, better improvements in the lens tilt angle were achieved through GRA. In conclusion, aiming to simultaneously improve the roundness of the lens holes and the overall flatness of the lens mount, the Taguchi–GRA method can achieve the optimization objectives. In terms of optical performance, by optimizing for roundness, it is possible not only to reduce the diameter of the light spot but also to simultaneously reduce the offset displacement of the light spot center on the screen. The method proposed in this paper can serve as an analytical model for the design and fabrication of plastic multilens mount.
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