Influenza is one of the most common human respiratory diseases, and represents a serious public health concern. However, the high mutability of influenza viruses has hampered vaccine development, and ...resistant strains to existing anti-viral drugs have also emerged. Novel anti-influenza therapies are urgently needed, and in this study, we describe the anti-viral properties of a Spirulina (Arthrospira platensis) cold water extract. Anti-viral effects have previously been reported for extracts and specific substances derived from Spirulina, and here we show that this Spirulina cold water extract has low cellular toxicity, and is well-tolerated in animal models at one dose as high as 5,000 mg/kg, or 3,000 mg/kg/day for 14 successive days. Anti-flu efficacy studies revealed that the Spirulina extract inhibited viral plaque formation in a broad range of influenza viruses, including oseltamivir-resistant strains. Spirulina extract was found to act at an early stage of infection to reduce virus yields in cells and improve survival in influenza-infected mice, with inhibition of influenza hemagglutination identified as one of the mechanisms involved. Together, these results suggest that the cold water extract of Spirulina might serve as a safe and effective therapeutic agent to manage influenza outbreaks, and further clinical investigation may be warranted.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
A new method for the synthesis of highly substituted naphthyridine‐based polyheteroaromatic compounds in high yields proceeds through rhodium(III)‐catalyzed multiple CH bond cleavage and CC and CN ...bond formation in a one‐pot process. Such highly substituted polyheteroaromatic compounds have attracted much attention because of their unique π‐conjugation, which make them suitable materials for organic semiconductors and luminescent materials. Furthermore, a possible mechanism, which involves multiple chelation‐assisted ortho CH activation, alkyne insertion, and reductive elimination, is proposed for this transformation.
Activated and annulated: A rhodium‐catalyzed one‐pot synthesis of highly substituted polyheteroaromatic compounds from N‐hydroxybenzamidines and alkynes is described. This reaction likely proceeds through multiple CH bond activation and annulation.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Summary
Background
While direct‐acting antivirals have been approved for treating hepatitis C, the guidelines highlight the importance of considering potential drug‐drug interactions between DAAs and ...concomitant medications.
Aim
To assess comorbidity prevalence, concomitant medication use and potential drug‐drug interactions between DAAs and concomitant medications for hepatitis C patients in Taiwan.
Methods
This cross‐sectional study enrolled 822 patients from May to August 2016 in Taiwan. Patient demographics, comorbidities and concomitant medications were evaluated by physician surveys.
Results
A total of 709 (86.3%) patients had ≥1 comorbidity; the most prevalent comorbidity categories were diseases of the digestive system (40.1%), circulatory system (38.7%) and endocrine/nutritional/metabolic diseases (35.2%). Elderly patients had more comorbidities. A total of 622 (75.7%) patients received ≥1 concomitant medication; the average number of concomitant medications was 3.2. The most common concomitant medication classes were cardiovascular (34.4%), gastrointestinal (25.7%) and central nervous system drugs (22.7%). Among patients without cirrhosis or with compensated cirrhosis, contraindications were most prevalent with paritaprevir/ritonavir/ombitasvir plus dasabuvir, daclatasvir/asunaprevir and glecaprevir/pibrentasvir (13.3%, 6.0% and 5.4% respectively), and least prevalent with sofosbuvir, sofosbuvir/daclatasvir, sofosbuvir/ledipasvir and sofosbuvir/velpatasvir (0.8%, 1.3%, 1.4% and 2.1% respectively). Sofosbuvir‐based regimens had no contraindications in patients with decompensated cirrhosis.
Conclusion
Our population represented an elderly demographic, with a high prevalence of comorbidities and widespread use of concomitant medications. The potential drug‐drug interactions between these concomitant medications and DAA regimens differed, with the fewest potential interactions with sofosbuvir‐based regimens.
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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
A thermally activated delayed fluorescent (TADF) emitter (DMAC-TRZ) was reported either as the emitting dopant in a host or as the non-doped (neat) emitting layer to achieve high EL EQEs of up to ...26.5% and 20% in OLEDs, respectively.
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.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Many second-line therapies are recently approved for patients with advanced hepatocellular carcinoma (HCC), in whom protein malnutrition is prevalent that would affect treatment outcomes. In this ...study, we aimed to investigate the role of pre-sarcopenia and muscle restoration in patients with sorafenib-failed advanced HCC. From August 2012 to March 2017, 385 patients who developed radiology-proven HCC progression after sorafenib treatment were enrolled in the study. Pre-sarcopenia is defined as transverse psoas muscle thickness per body height < 16.8 mm/m, which was prevalent (64.7%) in our patients. Age > 60 years, female gender, and body mass index < 22 kg/m
were independent predictors to the development of pre-sarcopenia. Patients with muscle depletion had significantly worse post-progression survival (PPS) compared with their counterparts (median PPS: 3.8 vs. 5.8 months, p = 0.003), particularly in those with intermediate liver reserves (Child-Pugh class B or Albumin-bilirubin grade 2). Besides, pre-sarcopenia independently predicted post-progression mortality in sorafenib-failed HCC (hazard ratio: 1.340, p = 0.012). In patients who developed pre-sarcopenia before sorafenib treatment, muscle restoration was associated with a longer PPS compared with their counterparts (6.3 vs. 3.6 months, p = 0.043). In conclusion, pre-sarcopenia independently determined the outcomes of sorafenib-failed HCC. Nutrition support to restore muscle mass would prolong survival for higher-risk patients.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Objectives
Sonoelastography has been increasingly used to investigate musculoskeletal disorders. The aim of this meta-analysis was to investigate the utility of sonoelastography in diagnosing rotator ...cuff tendon pathology and pertinent disorders.
Methods
Searching through PubMed and Embase, we systemically reviewed clinical studies in which sonoelastography has been used for imaging rotator cuff tendon pathology and relevant disorders. The primary outcome was the standardized mean difference (SMD) of tendon elasticity between shoulders (or patients) with and without the designated pathological conditions.
Results
A total of 11 cross-sectional studies were included in the meta-analysis. The supraspinatus and infraspinatus tendons assessed by shear wave sonoelastography were likely to be stiffer in shoulders with adhesive capsulitis, with a SMD of 2.103 (95% confidence interval (CI), − 0.151 to 4.357,
p
= 0.067) and a SMD of 1.548 (95% CI, − 0.032 to 3.127,
p
= 0.055), respectively. Regarding rotator cuff tendinopathy, there was no significant difference in the elasticity of supraspinatus tendons evaluated by shear wave velocity (SMD = − 0.107; 95% CI, − 0.524 to 0.310,
p
= 0.615) or strain ratios (SMD = 0.153, 95% CI, − 2.134 to 2.440,
p
= 0.896). Only one study used shear wave sonoelastography to investigate patients with rotator cuff tendon tears and found tendon that elasticity was similar between diseased and normal shoulders.
Conclusion
This meta-analysis revealed that supraspinatus and infraspinatus tendons tended to be stiffer in shoulders with adhesive capsulitis. Furthermore, no significant difference in tendon elasticity could be identified between shoulders with and without rotator cuff tendinopathy or tendon tears.
Key Points
• Supraspinatus and infraspinatus tendons are likely to have decreased elasticity in shoulders with adhesive capsulitis, as assessed by shear wave sonoelastography.
• There was no significant difference in tendon elasticity between shoulders with and without rotator cuff tendinopathy or tendon tears when evaluated by strain and shear wave sonoelastography.
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.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Converting solar energy into hydrogen energy using conjugated polymers (CP) is a promising solution to the energy crisis. Improving water solubility plays one of the critical factors in enhancing the ...hydrogen evolution rate (HER) of CP photocatalysts. In this study, a novel concept of incorporating hydrophilic side chains to connect the backbones of CPs to improve their HER is proposed. This concept is realized through the polymerization of carbazole units bridged with octane, ethylene glycol, and penta‐(ethylene glycol) to form three new side‐chain‐braided (SCB) CPs: PCz2S‐OCt, PCz2S‐EG, and PCz2S‐PEG. Verified through transient absorption spectra, the enhanced capability of PCz2S‐PEG for ultrafast electron transfer and reduced recombination effects has been demonstrated. Small‐ and wide‐angle X‐ray scattering (SAXS/WAXS) analyses reveal that these three SCB‐CPs form cross‐linking networks with different mass fractal dimensions (f) in aqueous solution. With the lowest f value of 2.64 and improved water/polymer interfaces, PCz2S‐PEG demonstrates the best HER, reaching up to 126.9 µmol h−1 in pure water‐based photocatalytic solution. Moreover, PCz2S‐PEG exhibits comparable performance in seawater‐based photocatalytic solution under natural sunlight. In situ SAXS analysis further reveals nucleation‐dominated generation of hydrogen nanoclusters with a size of ≈1.5 nm in the HER of PCz2S‐PEG under light illumination.
Pioneer examples of side‐chain‐bridged polymer photocatalysts, of tunable hydrophilicity of the side chains are presented. These polymers are capable of generating hydrogen using natural sunlight in seawater‐based photocatalytic solution. The distinctive structural characteristics and impressive HER performance of the side‐chain‐bridged conjugated polymers suggest a potential avenue in the development of photocatalytic conjugated polymers.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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