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Purpose: Psoriasis, a common systemic inflammatory disorder, presents with gender-related differences in the quality of life (QoL) and treatment outcomes. This post hoc analysis from the Phase 3b SUPREME study explored gender-related differences in patient characteristics and efficacy of secukinumab 300 mg on Psoriasis Area and Severity Index (PASI) 75/90/100 and impact on QoL using the Dermatology Life Quality Index (DLQI) in patients with moderate to severe psoriasis through week 24., Patients and Methods: The proportion of patients achieving PASI 75/90/100 was computed using a nonresponder imputation approach. Differences between cohorts were analyzed using a logistic regression model. The mean change from baseline in DLQI was computed using the Wilcoxon test., Results: Among the 433 patients (males: 71.6%), females had a higher DLQI than males at baseline (13.1 vs 9.5; P <0.0001). Males had a slightly higher response for PASI 90 than females at week 16 (80.7% vs 78.1%; P =0.0779) and 24 (83.2% vs 79.7%; P =0.0319). No differences were observed between genders in PASI 100/75 responses at week 24. Both genders showed an improvement in DLQI with secukinumab at week 24 (-10.9 vs -8.1, respectively, in females vs males; P =0.0004)., Conclusion: In summary, secukinumab was effective in the treatment of psoriasis, irrespective of gender., Competing Interests: L. Stingeni has acted as a speaker and board member for AbbVie, Eli Lilly, Novartis, Almirall, Celgene, Sanofi, and Janssen; G. Malara has acted as a speaker and consultant for AbbVie, Janssen, Amgen, Sanofi, Novartis, Eli Lilly, and UCB Pharma; A. Conti has acted as a consultant for AbbVie, Abbott, Amgen, Celgene, Eli Lilly, Janssen Cilag, Leo Pharma, MSD, Novartis, Sandoz, Schering Plough, UCB Pharma, and Wyeth; C.G. Carrera has reported collaboration with Novartis, AbbVie, Janssen, Lilly, and Leo Pharma; M. Burlando has served as a speaker and consultant for AbbVie, Janssen, Amgen, Novartis, Eli Lilly, and UCB Pharma; P. Malagoli has acted as a consultant or had advisory board agreements for Janssen, Amgen, AbbVie, UCB, Novartis, Lilly, Almirall, and Leo Pharma; M.L. Musumeci has served as a consultant/investigator for AbbVie, Eli Lilly, Janssen Cilag, Novartis, and Biogen; F. Bardazzi has acted as a speaker and/or consultant for Almirall, AbbVie, Celgene, Janssen, Eli Lilly, UCB Pharma, and Leo Pharma; V. Brazzelli has acted as a consultant and congress guest for Janssen Cilag SpA, Novartis, and Sanofi Genzyme; P. Amerio has received honoraria and is on the advisory board of Sanofi, Jansen, Novartis, Pfizer, Celgene, and Eli Lilly; C. De Simone has acted as a speaker and consultant for Almirall, AbbVie, Janssen, Celgene, Leo Pharma, Novartis, Eli Lilly, and UCB Pharma; S. Trevisini has served as a speaker for AbbVie, Novartis, and Janssen; A. Balato has served as speaker and/or consultant for AbbVie, Lilly, and Sanofi; M. Megna has served as a speaker or consultant for AbbVie, Eli Lilly, Novartis, Janssen, and Leo Pharma; M. Bartezaghi employees of Novartis; A. Rausa was an employee of Novartis during study conduct and manuscript submission. She approved the final version to be submitted while she was working for Novartis; E. Aloisi and R. Orsenigo are employees of Novartis; A. Costanzo has served as a speaker and consultant for AbbVie, Eli Lilly, Novartis, Almirall, Celgene, Sanofi, Janssen, and Pfizer. The authors report no other conflicts of interest in this work., (© 2023 Stingeni et al.)

A high rate of thromboembolism and a high risk of death have been reported regarding hospitalized patients with coronavirus disease 2019 (COVID-19). Recently, we noticed that clinicians in some comparative studies used direct oral anticoagulants (DOACs) to prevent thromboembolism in patients with COVID-19. However, it is uncertain whether DOACs are better than recommended heparin for hospitalized patients with COVID-19. Therefore, a direct comparison of the prophylactic effects and safety between DOACs and heparin is needed. We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library from 2019 to December 1, 2022. Randomized controlled trials or retrospective studies comparing the efficacy or safety of DOACs with that of heparin in preventing thromboembolism for hospitalized patients with COVID-19 were included. We assessed endpoints and publication bias using Stata 14.0. Five studies comprising 1360 hospitalized COVID-19 patients with mild to moderate cases were identified in the databases. Comparing the embolism incidence, we found that DOACs had a better effect than heparin, mainly low-molecular-weight heparin (LMWH), in preventing thromboembolism (risk ratio [RR] = 0.63, 95% confidence interval [CI] [0.43-0.91], P  = 0.014). Considering safety, DOACs resulted in less bleeding than heparin during hospitalization (RR = 0.52, 95% CI [0.11-2.44], P  = 0.411). Similar mortality was discovered in the 2 groups (RR = 0.94, 95% CI [0.59-1.51], P  = 0.797). In noncritically hospitalized patients with COVID-19, DOACs are superior to heparin, even LMWH, in preventing thromboembolism. Compared with heparin, DOACs have a lower trend of bleeding and yield a similar mortality rate. Therefore, DOACs may be a better alternative for patients with mild to moderate COVID-19.

With the accelerated construction of the smart grid, new energy sources such as photovoltaic and wind power are connected to the grid. In addition to power frequency, the current signal of power grid also includes several DC signals, as well as medium-high and high-frequency transient signals. Traditional current sensors for power grids are bulky, have a narrow measurement range, and cannot measure both AC and DC at the same time. Therefore, this paper designs a non-intrusive, AC-DC wide-bandwidth current sensor based on the composite measurement principle. The proposed composite current detection scheme combines two different isolation detection technologies, namely tunneling reluctance and the Rogowski coil . These two current sensing techniques are complementary (tunneling magnetoresistive sensors have good low-frequency characteristics and Rogowski coils have good high-frequency characteristics, allowing for a wide detection bandwidth). Through theoretical and simulation analysis, the feasibility of the composite measurement scheme was verified. The prototype of composite current sensor was developed. The DC and AC transmission characteristics of the sensor prototype were measured, and the sensitivity and linearity were 11.96 mV/A, 1.14%, respectively. Finally, the sweep current method and pulse current method experiments prove that the designed composite current sensor can realize the current measurement from DC to 17 MHz.

Objective: The prognosis value of fibrosis-4 score (FIB-4) in COVID-19 is controversial. Hence, we conducted a systematic review and meta-analysis to investigate the association between the FIB-4 index and COVID-19 disease progression., Methods: We performed meta-analysis using the PubMed, Embase, and Cochrane databases. A fixed- or random-effects model was used for evaluating heterogeneity., Results: Thirteen studies were included. The meta-analysis of unadjusted results showed that compared to lower FIB-4 index, patients with higher FIB-4 index had increased odds of mortality (OR=5.1, 95%CI 3.67-7.09; P <0.001), ICU admission (OR=2.32, 95%CI: 1.65-3.25, P <0.00001) and need for mechanical ventilator support (OR=3.51, 95%CI: 2.1-5.85, P <0.001). In addition, the meta-analysis of adjusted results showed patients with higher FIB-4 index was associated with increased risk of mortality (OR=3.01, 95%CI: 2.21-4.09, P <0.001) and need for mechanical ventilator support (OR=3.76, 95%CI: 2.08-6.82, P <0.001) compared to patients with lower FIB-4 index., Conclusions: This meta-analysis indicated that high FIB-4 index score was associated with the severity and mortality in COVID-19 infected patients., (© 2022 by the Association of Clinical Scientists, Inc.)

Background: Bactrocera dorsalis is a notorious pest and spraying of insecticides has been the major approach to controlling its damage. However, insecticide abuse has led to negative impacts on public health and insecticide resistance; hence, sustainable strategies, such as bait stations, need to be developed and taken into account for B. dorsalis management. In this study, we integrated insecticide, sugar, olfactory and visual elements into a wax matrix to formulate a long-lasting bait station. We determined its efficacy against B. dorsalis under field conditions., Results: The optimal bait station was a wax matrix incorporated with 1% spinetoram, 1% yellow pigment, and 3% ammonium acetate, and was spherical in shape with a 6 cm diameter. The longevity of this bait station was at least 10 weeks under field conditions. In a release and recapture experiment performed in Orchard 1, the bait stations were as effective as bait spray in controlling sterile fly populations, and more effective than the control. In a 2-year field trial conducted in Orchard 2, the number of female B. dorsalis and fruit infestation in the area where bait stations had been deployed was similar to the areas treated with cover spray. In Orchard 3, deployment of bait stations combined with chemical cover spray treatment decreased the population of female B. dorsalis and fruit damage more effectively than cover spray alone., Conclusions: Overall, wax-based bait stations can be regarded as a viable alternative to insecticides or a synergistic method for managing B. dorsalis. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

The COVID-19 pandemic continues to have profound health, social, psychological, and economic ramifications. Infection by COVID-19 has been of concern in people who use opioids, as opioid use has been known to mediate immunosuppression and is associated with respiratory depression and end-organ damage. With differing modalities of opioid usage, the association between opioids and COVID-19 outcomes is not well understood. We performed a comprehensive systematic search of seven health science databases, including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Data, up to December 15, 2021. We identified a total of five related articles, which were included in this study. The meta-analysis showed that opioids have a significant association with ICU admission for COVID-19 patients (OR = 5.41, 95%CI: 1.85 to 15.79, P = 0.002). Use of opioids was also associated with higher mortality among patients with COVID-19 compared to non-users (OR = 2.74, 95%CI: 1.34 to 5.62, P = 0.034), while use of opioids was not significantly associated with need for mechanical ventilation (OR = 3.68, 95%CI: 0.85 to 15.90, P = 0.081). Furthermore, the adjusted analysis indicated that COVID-19 patients with a history of opioid use were more likely to be admitted to the ICU (OR = 3.57, 95%CI: 3.05 to 4.17, P<0.001) and have higher mortality rates (OR = 1.72, 95%CI: 1.09 to 2.72, P = 0.02), while there was no significant association with need for mechanical ventilation (OR = 2.09, 95%CI: 0.77 to 5.64, P = 0.146). Significant heterogeneity existed across the included studies. Patients using opioids with COVID-19 were at higher risk of ICU admission and mortality. Prospective studies are required to confirm these findings., Competing Interests: Declaration of Competing Interest None of the authors have conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The administration of intravenous vitamin C (IV-VC) in treating patients with coronavirus disease 2019 (COVID-19) is still highly controversial. There have been no previous studies on the effect of IV-VC on the severity and mortality of COVID-19. Hence, we conducted a systematic review and meta-analysis to compare the disease severity and mortality in patients with COVID-19 who promptly received IV-VC treatment vs those who did not. We performed a comprehensive systematic search of seven health science databases, including PubMed, Embase, Cochrane Library, MEDLINE, Web of Science, China National Knowledge Infrastructure, and Wanfang Data, up to June 23, 2021. We identified a total of seven related articles, which were included in this study. This meta-analysis showed that IV-VC treatment did not affect disease severity compared with placebo treatment or usual care (odds ratio [OR], 0.70; 95% CI, 0.45 to 1.07; P = 0.10). In addition, no statistically significant difference in mortality was observed between patients who received IV-VC treatment and those who did not (OR, 0.64; 95% CI, 0.41 to 1.00; P = 0.05). Moreover, the adjusted meta-analysis revealed that the use of IV-VC did not influence disease severity (OR, 0.67; 95% CI, 0.34 to 1.31; P = 0.242) or mortality (OR, 1.02; 95% CI, 0.75 to 1.40; P = 0.877) in comparison with a control group. The results of this meta-analysis demonstrated that short-term IV-VC treatment did not reduce the risk of severity and mortality in patients with COVID-19., (© 2022 American Society for Parenteral and Enteral Nutrition.)

Glyconanomaterials with unique nanoscale property and carbohydrate functionality show vast potential in biological and biomedical applications. We investigated the interactions of noncovalent complexes of single-wall carbon nanotubes that are wrapped by disaccharide lactose-containing glycopolymers with the specific carbohydrate-binding proteins. The terminal galactose (Gal) of glycopolymers binds to the specific lectin as expected. Interestingly, an increased aggregation of nanotubes was also observed when interacting with a glucose (Glc) specific lectin, likely due to the removal of Glc groups from the surface of nanotubes resulting from the potential binding of the lectin to the Glc in the glycopolymers. This result indicates that the wrapping conformation of glycopolymers on the surface of nanotubes potentially allows improved accessibility of the Glc for specific lectins. Furthermore, it shows that the interaction between Glc groups in the glycopolymers and nanotubes play a key role in stabilizing the nanocomplexes. Overall, our results demonstrate that nanostructures can enable conformation-dependent interactions of glycopolymers and proteins and can potentially lead to the creation of versatile optical sensors for detecting carbohydrate-protein interactions with enhanced specificity and sensitivity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 DiLillo, Chan, Sun and Ao.)

Background: New evidence from studies on risk factors for mortality in hemodialysis (HD) patients with COVID-19 became available. We aimed to review the clinical risk factors for fatal outcomes in these patients., Methods: We performed meta-analysis using the PubMed, EMBASE, and Cochrane databases. A fixed- or random-effects model was used for calculating heterogeneity. We used contour-enhanced funnel plot and Egger's tests to assess potential publication bias., Results: Twenty-one studies were included. The proportion of males was lower in the survivor group than in the non-survivor group (OR = 0.75, 95% CI [0.61, 0.94]). The proportion of respiratory diseases was significantly lower in the survivor group than in the non-survivor group (OR = 0.42, 95% CI [0.29, 0.60]). The proportion of patients with fever, cough, and dyspnea was significantly lower in the survivor group (fever: OR = 0.53, 95% CI [0.31, 0.92]; cough: OR = 0.50, 95% CI [0.38, 0.65]; dyspnea: OR = 0.25, 95% CI [0.14, 0.47]) than in the non-survivor group. Compared with the non-survivor group, the survivor group had higher albumin and platelet levels and lower leucocyte counts., Conclusions: Male patients might have a higher risk of developing severe COVID-19. Comorbidities, such as respiratory diseases could also greatly influence the clinical prognosis of COVID-19. Clinical features, such as fever, dyspnea, cough, and abnormal platelet, leucocyte, and albumin levels, could imply eventual death. Our findings will help clinicians identify markers for the detection of high mortality risk in HD patients at an early stage of COVID-19.

Introduction The number of cancer cases among the elderly continue to increase as the worldwide population ages. This patient subset is underrepresented in clinical trials, partly because of unresolved uncertainties about age-associated tolerabilities and antitumor activities. We reviewed phase 1 trial data to study tolerance and efficacy of novel agents used for treatment of elderly patients with cancer. Methods Data from 773 consecutive evaluable patients in 85 phase 1 clinical trials (2008-2016) at START Madrid-CIOCC were analyzed according to age, with respect to objective response, survival, and toxicity. Results The mean age was 58.7 (range: 18-87) years; 260 (33.6%) patients were >65 y (elderly group). One hundred thirty-seven (17.8%) patients received immunotherapy drugs, 308 (39.8%) received targeted agents, and 328 (42.4%) received chemotherapy. No statistically significant differences in overall survival, objective response, or severe toxicity rates were found according to treatment type. Similar toxicities and clinical activities were found between the two age subgroups; 18.8% of the elderly and 20.7% of the younger patients experienced severe hematological toxicity (p=0.5), and 30.2% and 32.7%, respectively, experienced severe non-hematological toxicity (p=0.4). Regarding antitumor activity, 12.4% of the elderly and 15% of the younger patients achieved objective responses (p=0.41). There were no significant between-group differences in overall survival (9.7 versus 11.5 months, respectively, p=0.1) or progression-free survival (2.3 versus 2.2 months, respectively, p=0.7). Conclusions This retrospective study found that elderly and younger populations had comparable antitumor activities and toxicity profiles. These results support including elderly patients with cancer in early-phase trials., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Effectively translating the promising properties of boron nitride nanotubes (BNNTs) into macroscopic assemblies has vast potential for applications, such as thermal management materials and protective fabrics against hazardous environment. We spun fibers from aqueous dispersions of BNNTs in polyvinyl alcohol (PVA) solutions by a wet spinning method. Our results demonstrate that BNNTs/PVA fibers exhibit enhanced mechanical properties, which are affected by the nanotube and PVA concentrations, and the coagulation solvent utilized. Compared to the neat PVA fibers, we obtained roughly 4.3-, 12.7-, and 1.5-fold increases in the tensile strength, Young's modulus, and toughness, respectively, for the highest performing BNNTs/PVA fibers produced from dispersions containing as low as 0.1 mass% of nanotube concentration. Among the coagulation solvents tested, we found that solvents with higher polarity such as methanol and ethanol generally produced fibers with improved mechanical properties, where the fiber toughness shows a strong correlation with solvent polarity. These findings provide insights into assembling BNNTs-based fibers with improved mechanical properties for developing unique applications., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)

Processing boron nitride nanotubes (BNNTs) for applications ranging from nanomedicine to electronics generally requires dispersions of nanotubes that are stable in various compounds and solvents. We show that alcohol/water cosolvents, particularly isopropyl alcohol (IPA), are essential for the complexation of BNNTs with DNA under mild bath sonication. The resulting DNA-wrapped BNNT complexes are highly stable during purification and solvent exchange from cosolvents to water, providing potential for the versatile liquid-phase processing of BNNTs. Via molecular dynamics simulations, we demonstrate that IPA assists in the solvation of BNNTs due to its pseudosurfactant nature by verifying that water is replaced in the solvation layer as IPA is added. We quantify the solvation free energy of BNNTs in various IPA/water mixtures and observe a nonmonotonic trend, highlighting the importance of utilizing solvent-nanotube interactions in nanomaterial dispersions. Additionally, we show that nanotube lengths can be characterized by rheology measurements via determining the viscosity of dilute dispersions of DNA-BNNTs. This represents the bulk sample property in the liquid state, as compared to conventional imaging techniques that require surface deposition and drying. Our results also demonstrate that BNNT dispersions exhibit the rheological behavior of dilute Brownian rigid rods, which can be further exploited for the controlled processing and property enhancement of BNNT-enabled assemblies such as films and fibers.

Background: The effect of solid organ transplantation (SOT) on the severity and mortality of coronavirus disease 2019 (COVID-19) remained controversial. There is still no consensus on whether solid organ transplantation (SOT) recipients with COVID-19 are at greater risk of developing severe or fatal COVID-19. Therefore, we conducted a systematic review and meta-analysis to investigate the association between SOT, severe COVID-19 illness, and mortality., Methods: A systemically comprehensive search in Pubmed, Embase, the Cochrane Library, Web of Science, and China National Knowledge Infrastructure was performed for relevant studies and articles. Consequently, we pooled the odds ratio (OR) from individual studies and performed heterogeneity, quality assessment and subgroup/sensitivity analysis., Results: A total number of 15 articles with 265,839 participants were included in this study. Among the total number of participants, 1485 were SOT recipients. The meta-analysis results showed that transplant patients with COVID-19 were remarkably associated with a higher risk of intensive care unit admission than non-transplant patients (OR = 1.57, 95%CI: 1.07 to 2.31, P = 0.02). On the other hand, there were no statistically significant differences between SOT recipients and non-SOT recipients in mechanical ventilation need (OR = 1.55, 95%CI: 0.98 to 2.44, P = 0.06). In addition, we found that SOT recipients with COVID-19 had 1.40-fold increased odds of mortality than non-SOT recipients (OR = 1.40, 95%CI: 1.10 to 1.79, P = 0.007). Moreover, pooled analysis of adjusted results revealed that SOT recipients had a greater risk of mortality compared with non-SOT patients (HR = 1.54, 95%CI: 1.03 to 2.32, P = 0.037)., Limitations: The main limitations in our study are attributed to the relatively small sample size, short follow-up period, and the fact that most of the studies included were retrospective in design., Conclusions: The results of this study indicate that SOT recipients with COVID-19 had a more significant risk of COVID-19 severity and mortality than the general population., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Since China's reform and opening-up in 1978, the income of rural residents has increased when compared with that of urban residents. However, the income growth rate of farmers is relatively low, and the income gap between urban and rural areas is widening. Using a sample of 1,325 large-scale farming households in Lin'an, this study constructs a theoretical path for how the level of vertical integration and an organization model affect farmers' income levels and empirically tests the path using a mediation effect analysis model. The results indicate that organization models and vertical integration are important factors that affect farmers' income levels. The total income and agricultural operation income of farmers who participate in agricultural operation organizations are greater than that of farmers who do not participate in an operation organization. In addition, the total income and agricultural operation income of farmers who produce and process and those who produce, process, and sell are higher than those of farmers who only produce. A farmers' organization model has both a direct and an indirect positive influence on their income level, with the indirect positive influence coming through the mediating variable of vertical integration. The application of the organizational model can promote the growth of rural households' total family income and agricultural income by 13.48% and 14.48% respectively, consisting of direct increases of 9.67% and 10.19%, and indirect increases of 3.81% and 4.29% through vertical integration. The results also show that access to credit, agricultural technology training, and the farmer's education level have significant positive impacts on farming income levels. The findings suggest ways to increase farmers' income by perfecting agricultural management organization systems, promoting agricultural industrialization, strengthening rural financial support, improving agricultural technical training for farmers, and increasing their level of education., Competing Interests: There are no conflicts of interest to declare.

Despite the rationale that early anti-platelet would lower the risk of major organ dysfunction, the effectiveness of this approach remains controversial. Therefore, we perform a systematic review and meta-analysis to investigate the effect of antiplatelet treatments on patients with COVID-19 infection. An electronic search was carried out in Pubmed, Embase, Cochrane library, Web of Science, MEDLINE, Wanfang and China National Knowledge Infrastructure (CNKI). Meta-analysis and statistical analyses were completed with using the RevMan 5.3 and Stata 12.0. A total of 9 articles representing data from 5970 participants were included in this study. The meta-analysis showed antiplatelet agents were not associated with higher risk of severe COVID-19 disease (OR = 0.98, 95%CI: 0.64 to 1.50, P = 0.94; I 2 = 65%), while an adjusted analysis indicated that antiplatelet agents was not associated with an increased risk of mortality (OR = 0.65, 95%CI: 0.40 to 1.06, P = 0.498; I 2 = 0%). The results of this study reveal that while there is no significant benefit on mortality demonstrated with the use of antiplatelet agents, the upper bound of the confidence interval suggests that there is unlikely to be a compelling risk of harm associated with this practice. The benefit and risk of the use of antiplatelet agents should be fully considered especially in the presence of thrombocytopenia status in patients with COVID-19., Competing Interests: Declaration of Competing Interest None of the authors have conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: It is currently controversial whether neutrophil-to-lymphocyte ratio (NLR) has a prognostic role in patients with chronic kidney disease (CKD). We aimed to investigate whether NLR was an independent predictor of cardiovascular or all-cause mortality in CKD patients with or without hemodialysis by performing a meta-analysis., Methods: Pubmed, Embase, and Cochrane Library databases are systematically searched for relevant literature that investigated NLR and subsequent cardiovascular or all-cause mortality risk in CKD with or without dialysis. Pooled hazard risk (HR) with 95% confidence interval (CI) was calculated for the high vs. low NLR category., Results: A total of thirteen studies enrolling 116,709 patients were identified and analyzed. In summary, high NLR was associated with an increased risk of all-cause mortality (HR 1.93, 95% CI 1.87-2.00; P < 0.00001) and cardiovascular mortality (HR 1.45, 95% CI 1.18-1.79, P < 0.001). Subgroup analysis indicated that high NLR are independently associated with all-cause mortality risk in dialysis patients (HR 1.94, 95% CI 1.87-2.01; P < 0.00001)., Conclusions: This meta-analysis indicates a high NLR is related to all-cause mortality and cardiovascular mortality in patients with chronic kidney disease. Dialysis patients with high NLR are candidates at high risk of mortality to allow for earlier interventions. Further large scale and more rigorously designed studies are warranted to confirm the prognostic value of NLR in the different stages of CKD.

Introduction: Phase I trials aim to determine the maximum-tolerated dose of a particular drug while minimizing the number of patients exposed to either sub-therapeutic doses or severe toxicity. Thus, patient selection for phase I trials is a key component of any clinical trial design. Though several studies have been made to address this issue, patient selection still represents a major clinical challenge that needs further investigation., Methods: Twenty-nine baseline clinical and analytical characteristics of 773 consecutive patients treated in phase I trials between 2008 and 2016 in START Madrid-CIOCC were analysed and correlated to objective response (OR), progression-free survival, median overall survival, toxicity, and treatment type. The ones associated to OR in the univariate analysis were included in the stepwise logistic regression multivariate and Cox analysis. The statistically significant ones were included in a predictive score (named here as the Madrid score) of antitumour activity., Results: Body mass index (BMI) >25 (p = 0.027), two or less previous lines of treatment (p = 0.007), and normal levels of alkaline phosphatase (ALP) (p = 0.007) were found to positively correlate to radiological response. A Madrid score was generated using these three factors as predictive parameters: compared to a score of 2-3 (where 2 or 3 of these variables are altered), a score of 0-1 is associated with longer survival time (11.6 vs. 8.6 months; p = 0.005) and overall response (17 vs. 7.6%; p = 0.003)., Conclusion: The predictive Madrid score, based on the BMI, number of prior lines of treatment, and ALP levels, might be helpful to accurately select patients who would benefit from oncology phase I clinical trials., (© 2021 S. Karger AG, Basel.)

Cold storage and heat exposure are crucial components of tephritid fruit fly mass-rearing programs, as they influence the development and fitness traits of produced flies. This work investigated the effects of cold storage on the pupal developmental parameters and quality of Bactrocera dorsalis (Hendel) genetic sexing strain (GSS) adults. Furthermore, the impact of short-term thermal exposure on the fecundity of B. dorsalis (GSS) that also underwent pupal cold storage was examined. Our results show that pupal development time, emergence rate, partial emergence rate, flight ability and fecundity were significantly affected by low temperature and pupal age and their interaction. Pupal cold storage did not pose negative impacts on the mating competition and response to methyl eugenol (ME) in the males. In addition, compared with the adults that were subjected to the same pupal storage protocol (five-day-old pupae stored at 13 °C), adult exposure to 41 °C for 1 h showed significant reparative effects on fecundity. In summary, the cold storage procedure of B. dorsalis (GSS) pupae has the potential to improve the flexibility and efficiency of mass-rearing schedules. Furthermore, short-term thermal exposure showed reparative effects on the fecundity costs induced by pupal cold storage in B. dorsalis (GSS).

Hydrogen sulfide (H 2 S) is a gasotransmitter and a potential therapeutic agent. However, molecular targets relevant to its therapeutic actions remain enigmatic. Sulfide-quinone oxidoreductase (SQR) irreversibly oxidizes H 2 S. Therefore, SQR is assumed to inhibit H 2 S signaling. We now report that SQR-mediated oxidation of H 2 S drives reverse electron transport (RET) at mitochondrial complex I, which, in turn, repurposes mitochondrial function to superoxide production. Unexpectedly, complex I RET, a process dependent on high mitochondrial membrane potential, induces superoxide-dependent mitochondrial uncoupling and downstream activation of adenosine monophosphate-activated protein kinase (AMPK). SQR-induced mitochondrial uncoupling is separated from the inhibition of mitochondrial complex IV by H 2 S. Moreover, deletion of SQR, complex I, or AMPK abolishes therapeutic effects of H 2 S following intracerebral hemorrhage. To conclude, SQR mediates H 2 S signaling and therapeutic effects by targeting mitochondrial electron transport to induce mitochondrial uncoupling. Moreover, SQR is a previously unrecognized target for developing non-protonophore uncouplers with broad clinical implications., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Stable dispersions of single-wall carbon nanotubes (SWCNTs) by biopolymers in an aqueous environment facilitate their potential biological and biomedical applications. In this report, we investigated a small library of precision synthesized glycopolymers with monosaccharide and disaccharide groups for stabilizing SWCNTs via noncovalent complexation in aqueous conditions. Among the glycopolymers tested, disaccharide lactose-containing glycopolymers demonstrate effective stabilization of SWCNTs in water, which strongly depends on carbohydrate density and polymer chain length as well. The introduction of disaccharide lactose potentially makes glycopolymers less flexible as compared to those containing monosaccharide and facilitates the wrapping conformation of polymers on the surface of SWCNTs while preserving intrinsic photoluminescence of nanotubes in the near-infrared region. This work demonstrates the synergistic effects of the identity of carbohydrate pendant groups and polymer chain length of glycopolymers on stabilizing SWCNTs in water, which has not been achieved previously.

Background: Transfusion-dependent haemoglobinopathies require lifelong iron chelation therapy with one of the three iron chelators (deferiprone, deferasirox, or deferoxamine). Deferasirox and deferiprone are the only two oral chelators used in adult patients with transfusion-dependent haemoglobinopathies. To our knowledge, there are no randomised clinical trials comparing deferiprone, a less expensive iron chelator, with deferasirox in paediatric patients. We aimed to show the non-inferiority of deferiprone versus deferasirox., Methods: DEEP-2 was a phase 3, multicentre, randomised trial in paediatric patients (aged 1 month to 18 years) with transfusion-dependent haemoglobinopathies. The study was done in 21 research hospitals and universities in Italy, Egypt, Greece, Albania, Cyprus, Tunisia, and the UK. Participants were receiving at least 150 mL/kg per year of red blood cells for the past 2 years at the time of enrolment, and were receiving deferoxamine (<100 mg/kg per day) or deferasirox (<40 mg/kg per day; deferasirox is not registered for use in children aged <2 years so only deferoxamine was being used in these patients). Any previous chelation treatment was permitted with a 7-day washout period. Patients were randomly assigned 1:1 to receive orally administered daily deferiprone (75-100 mg/kg per day) or daily deferasirox (20-40 mg/kg per day) administered as dispersible tablets, both with dose adjustment for 12 months, stratified by age (<10 years and ≥10 years) and balanced by country. The primary efficacy endpoint was based on predefined success criteria for changes in serum ferritin concentration (all patients) and cardiac MRI T2-star (T2*; patients aged >10 years) to show non-inferiority of deferiprone versus deferasirox in the per-protocol population, defined as all randomly assigned patients who received the study drugs and had available data for both variables at baseline and after 1 year of treatment, without major protocol violations. Non-inferiority was based on the two-sided 95% CI of the difference in the proportion of patients with treatment success between the two groups and was shown if the lower limit of the two-sided 95% CI was greater than -12·5%. Safety was assessed in all patients who received at least one dose of study drug. This study is registered with EudraCT, 2012-000353-31, and ClinicalTrials.gov, NCT01825512., Findings: 435 patients were enrolled between March 17, 2014, and June 16, 2016, 393 of whom were randomly assigned to a treatment group (194 to the deferiprone group; 199 to the deferasirox group). 352 (90%) of 390 patients had β-thalassaemia major, 27 (7%) had sickle cell disease, five (1%) had thalassodrepanocytosis, and six (2%) had other haemoglobinopathies. Median follow-up was 379 days (IQR 294-392) for deferiprone and 381 days (350-392) for deferasirox. Non-inferiority of deferiprone versus deferasirox was established (treatment success in 69 [55·2%] of 125 patients assigned deferiprone with primary composite efficacy endpoint data available at baseline and 1 year vs 80 [54·8%] of 146 assigned deferasirox, difference 0·4%; 95% CI -11·9 to 12·6). No significant difference between the groups was shown in the occurrence of serious and drug-related adverse events. Three (2%) cases of reversible agranulocytosis occurred in the 193 patients in the safety analysis in the deferiprone group and two (1%) cases of reversible renal and urinary disorders (one case of each) occurred in the 197 patients in the deferasirox group. Compliance was similar between treatment groups: 183 (95%) of 193 patients in the deferiprone group versus 192 (97%) of 197 patients in the deferisirox group., Interpretation: In paediatric patients with transfusion-dependent haemoglobinopathies, deferiprone was effective and safe in inducing control of iron overload during 12 months of treatment. Considering the need for availability of more chelation treatments in paediatric populations, deferiprone offers a valuable treatment option for this age group., Funding: EU Seventh Framework Programme., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Multiple myeloma is an incurable refractory hematologic malignancy arising from plasma cells in the bone marrow. Here we investigated miR-26a function in multiple myeloma and tested single-wall carbon nanotube delivery of miR-26a in vitro and in vivo . miR-26a was downregulated in patients with multiple myeloma cells compared with plasma cells from healthy donors. miR-26a overexpression inhibited proliferation and migration and induced apoptosis in multiple myeloma cell lines. To identify the targets of miR-26a, RPMI8226-V-miR-26-GFP and RPMI8226-V-GFP cells were cultured using stable isotope labeling by amino acids in cell culture (SILAC) medium, followed by mass spectrometry analysis. In multiple myeloma cells overexpressing miR-26a, CD38 protein was downregulated and subsequently confirmed to be a direct target of miR-26a. Depletion of CD38 in multiple myeloma cells duplicated the multiple myeloma inhibition observed with exogenous expression of miR-26a, whereas restoration of CD38 overcame the inhibition of miR-26a in multiple myeloma cells. In a human multiple myeloma xenograft mouse model, overexpression of miR-26a inhibited CD38 expression, provoked cell apoptosis, and inhibited cell proliferation. Daratumumab is the first CD38 antibody drug for monotherapy and combination therapy for patients with multiple myeloma, but eventually resistance develops. In multiple myeloma cells, CD38 remained at low level during daratumumab treatment, but a high-quality response is sustained. In daratumumab-resistant multiple myeloma cells, CD38 expression was completely restored but failed to correlate with daratumumab-induced cell death. Therefore, a therapeutic strategy to confer selection pressure to maintain low CD38 expression in multiple myeloma cells may have clinical benefit. SIGNIFICANCE: These results highlight the tumor suppressor function of miR-26a via its targeting of CD38 and suggest the therapeutic potential of miR-26a in patients with multiple myeloma., (©2020 American Association for Cancer Research.)

Organic color-center quantum defects in semiconducting carbon nanotube hosts are rapidly emerging as promising candidates for solid-state quantum information technologies. However, it is unclear whether these defect color-centers could support the spin or pseudospin-dependent excitonic fine structure required for spin manipulation and readout. Here we conducted magneto-photoluminescence spectroscopy on individual organic color-centers and observed the emergence of fine structure states under an 8.5 T magnetic field applied parallel to the nanotube axis. One to five fine structure states emerge depending on the chirality of the nanotube host, nature of chemical functional group, and chemical binding configuration, presenting an exciting opportunity toward developing chemical control of magnetic brightening. We attribute these hidden excitonic fine structure states to field-induced mixing of singlet excitons trapped at sp 3 defects and delocalized band-edge triplet excitons. These findings provide opportunities for using organic color-centers for spintronics, spin-based quantum computing, and quantum sensing.

Objectives: The aim of this study was to develop a method to determine hepatic and renal clearance of the 2 diastereoisomers (Gd-A, Gd-B) of Gd-EOB-DTPA separately., Materials and Methods: Between July 2017 and February 2018, 41 patients with hepatic disease were prospectively included. For each patient, 1 mL of iopromide (to determine glomerular filtration rate [GFR]) was coadministered with Gd-EOB-DTPA (Gd-A and Gd-B; 65:35 wt/wt). The plasma clearances of Gd-A (PCL-GdA) and Gd-B (PCL-GdB) as well as the iopromide (GFR) were generated by using dual plasma sampling method. Meanwhile, the patient's urine was collected for measurement of renal clearance of Gd-A (RCL-GdA) and Gd-B (RCL-GdB) to confirm its agreement with GFR. Hepatic clearances of Gd-A (HCL-GdA) and Gd-B (HCL-GdB) were calculated by subtracting the GFR from PCL-GdA and PCL-GdB, respectively, and were correlated with indocyanine green (ICG) 15 minutes retention rate (ICG R15). Pharmacokinetic parameters were compared between the two isomers and between Child-Pugh classifications using student's t test., Results: Within the group of 41 patients evaluated, both RCL-GdA and RCL-GdB demonstrated a good correlation and agreement to GFR (statistics shown in the main body). HCL-GdA demonstrated a strong negative correlation (r = -0.86, P < 0.001) with ICG R15 and was much higher than HCL-GdB (116.18 ± 75.48 vs 19.74 ± 14.24 mL/min, P < 0.001). HCL-GdB demonstrated a weak correlation (r = -0.26, P = 0.102) with ICG R15. HCL-GdA of noncirrhosis and Child-Pugh class A (151.74 ± 68.28 mL/min, n = 26) was higher than that of Child-Pugh class B (54.54 ± 39.13 mL/min, n = 15; P = 0.001)., Conclusions: A practical method was established for the determination of hepatic and renal clearance of the 2 isomers of Gd-EOB-DTPA. The 2 isomers have equal renal clearance and different hepatic clearance. The HCL-GdA may serve as a novel marker to reflect liver function reserve.

This study aims to evaluate several life-history traits of a T. drosophilae population from southern China and its parasitic preference of three Drosophila species. For mated T. drosophilae females, the mean oviposition and parasitization period were 27.20 and 37.80 d, respectively. The daily mean parasitization rate was 59.24% per female and the lifetime number of emerged progeny was 134.30 per female. Trichopria drosophilae females survived 37.90 and 71.61 d under host-provided and host-deprived conditions, respectively. To assess the potential for unmated reproduction in T. drosophilae , the mean oviposition and parasitization period of unmated females was 22.90 and 47.70 d, respectively. They had a daily mean parasitization rate of 64.68%, produced a total of 114.80 offspring over their lifetime, and survived 52 d. Moreover, T. drosophilae showed a preference towards D. suzukii based on the total number of emerged offspring under a choice test. Our findings indicate that T. drosophilae from southern China appears to be suitable for the control of D. suzukii in invaded areas, due to its reproductive potential.

Molecularly functionalized single-walled carbon nanotubes (SWCNTs) are potentially useful for fiber optical applications due to their room temperature single-photon emission capacity at telecommunication wavelengths. Several distinct defect geometries are generated upon covalent functionalization. While it has been shown that the defect geometry controls electron localization around the defect site, thereby changing the electronic structure and generating new optically bright red-shifted emission bands, the reasons for such localization remain unexplained. Our joint experimental and computational studies of functionalized SWCNTs with various chiralities show that the value of mod(n-m,3) in an (n,m) chiral nanotube plays a key role in the relative ordering of defect-dependent emission energies. This dependence is linked to the complex nodal characteristics of electronic wave function extending along specific bonds in the tube, which justifies the defect-geometry dependent exciton localization. This insight helps to uncover the essential structural motifs allowing tuning the redshifts of emission energies in functionalized SWCNTs.

The nominal composition of Al 2 O 3 -Ce:Y 3 Mg 1.8 Al 1.4 Si 1.8 O 12 (A-Ce:YMASG) ceramic phosphors was fabricated by the vacuum sintering technique. The introduction of Al 2 O 3 as a second phase partially enters the crystal lattice, which was confirmed by the composition changing of the samples through x-ray diffraction measurement. An impurity phase of Y 4 MgSi 3 O 13 was observed in Ce:YMASG and disappeared with the introduction of Al 2 O 3 at the concentration of 10 wt. %. When the content of Al 2 O 3 increased to 30 and 50 wt. %, the second phase of Al 2 O 3 was measured with actual weight ratios of 7.72 and 20.55 wt. %, respectively. The third phase of MgAl 2 O 4 was found with the further addition of Al 2 O 3 at 70 wt. %; the weight ratios of Ce:YMASG, Al 2 O 3 , and MgAl 2 O 4 were 68.756, 18.457, and 12.787 wt. %, respectively. The luminescent characters of the samples were measured by the photoluminescence spectra and electroluminescent spectra. With the increase of Al 2 O 3 from 0 to 30 wt. %, the emission wavelength of Ce 3+ plummeted from 610 to 552 nm, and the luminous efficacy of the samples increased from 35 to 65 lm/W.

Background: Pituitary tumors are a heterogeneous group of lesions that are usually benign. Therefore, a proper understanding of the anatomy, physiology, and pathology is mandatory to achieve favorable outcomes. Accordingly, diagnostic tests and treatment guidelines should be determined and implemented. Thus, we decided to perform a multicenter study among Italian neurosurgical centers performing pituitary surgery to provide an actual depiction from the neurosurgical standpoint., Methods: On behalf of the SINch (Società Italiana di Neurochirurgia), a survey was undertaken with the participants to explore the activities in the field of pituitary surgery within 41 public institutions., Results: Of the 41 centers, 37 participated in the present study. The total number of neurosurgical procedures performed in 2016 was 1479. Most of the procedures were performed using the transsphenoidal approach (1320 transsphenoidal [1204 endoscopic, 53 microscopic, 53 endoscope-assisted microscopic] vs. 159 transcranial). A multidisciplinary tumor board is convened regularly in 32 of 37 centers, and a research laboratory is present in 18 centers., Conclusions: Diagnosing pituitary/hypothalamus disorders and treating them is the result of teamwork, composed of several diverse experts. Regarding neurosurgery, our findings have confirmed the central role of the transsphenoidal approach, with preference toward the endoscopic technique. Better outcomes can be expected at centers with a multidisciplinary team and a full, or part of a, residency program, with a greater surgical caseload., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The introduction of sp 3 defects into single-walled carbon nanotubes through covalent functionalization can generate new light-emitting states and thus dramatically expand their optical functionality. This may open up routes to enhanced imaging, photon upconversion, and room-temperature single-photon emission at telecom wavelengths. However, a significant challenge in harnessing this potential is that the nominally simple reaction chemistry of nanotube functionalization introduces a broad diversity of emitting states. Precisely defining a narrow band of emission energies necessitates constraining these states, which requires extreme selectivity in molecular binding configuration on the nanotube surface. We show here that such selectivity can be obtained through aryl functionalization of so-called 'zigzag' nanotube structures to achieve a threefold narrowing in emission bandwidth. Accompanying density functional theory modelling reveals that, because of the associated structural symmetry, the defect states become degenerate, thus limiting emission energies to a single narrow band. We show that this behaviour can only result from a predominant selectivity for ortho binding configurations of the aryl groups on the nanotube lattice.

The abnormal accumulation of lipids within the endolysosomal lumen occurs in many conditions, including lysosomal storage disorders, atherosclerosis, nonalcoholic fatty liver disease (NAFLD), and drug-induced phospholipidosis. Current methods cannot monitor endolysosomal lipid content in vivo, hindering preclinical drug development and research into the mechanisms linking endolysosomal lipid accumulation to disease progression. We developed a single-walled carbon nanotube-based optical reporter that noninvasively measures endolysosomal lipid accumulation via bandgap modulation of its intrinsic near-infrared emission. The reporter detected lipid accumulation in Niemann-Pick disease, atherosclerosis, and NAFLD models in vivo. By applying the reporter to the study of NAFLD, we found that elevated lipid quantities in hepatic macrophages caused by a high-fat diet persist long after reverting to a normal diet. The reporter dynamically monitored endolysosomal lipid accumulation in vivo over time scales ranging from minutes to weeks, indicating its potential to accelerate preclinical research and drug development processes., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Organic color centers are an emergent class of quantum emitters that hold vast potential for applications in bioimaging, chemical sensing, and quantum information processing. Here, we show that these synthetic color centers follow interesting structure-property relationships through comparative spectral studies of 14 purified single-walled carbon nanotube chiralities and 30 different functional groups that vary in electron-withdrawing capability and bonding configurations. The defect emission is tunable by as much as 400 meV in the near-infrared as a function of host structure and the chemical nature of the color centers. However, the emission energy is nearly free from chiral angle and family patterns of the nanotube host (although this strongly depends on the nanotube diameter), suggesting that a trapped exciton at the organic color centers to some degree electronically decouples from the one-dimensional semiconductor host. Our findings provide important insights for designing and controlling this new family of synthetic color centers., Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests.

Rationale and Objectives: This prospective study aimed to evaluate the diagnostic performance of dual-input computed tomography perfusion technique (DI-CTP) in identifying the bronchial-pulmonary artery fistula in patients tuberculosis with massive hemoptysis., Material and Methods: Twenty patients with tuberculosis with massive hemoptysis were enrolled from January 2015 to December 2015. The association between DI-CTP parameters and the diagnostic outcomes of digital subtraction angiography was assessed. Diagnostic efficacy of DI-CTP was evaluated by receiver operating curve (ROC) analyses using the diagnostic outcomes of digital subtraction angiography, which is the gold standard for identifying bronchial-pulmonary artery fistula., Results: Compared to lung segments with normal blood flow (n = 304), those with bronchial-pulmonary artery fistula (n = 164) had a reduced pulmonary flow value, perfusion index (PI) value, and an elevated bronchial artery (BF) value in the DI-CTP scan, which was further confirmed by multivariate logistic regression. ROC analysis showed that PI and bronchial artery has an excellent diagnostic performance (both area under the ROC curve > 0.9, P < .001) and high sensitivity and specificity (from 0.79 to 0.95 at the optimal cutoff). PI has the best diagnostic performance, with an overall diagnostic accuracy of 0.91., Conclusions: DI-CTP scan possesses the diagnostic value for detecting bronchial-pulmonary artery fistula in patients with tuberculosis with massive hemoptysis, providing an alternative diagnostic method., (Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Context: Few studies regarding palliative sedation (PS) have been carried out in home care (HC) setting. A comparison of PS rate and practices between hospice (HS) and HC is also lacking., Objectives: Comparing HC and HS settings for PS rate, patient clinical characteristics before and during PS, decision-making process, and clinical aspects of PS., Methods: About 38 HC/HS services in Italy participated in a multicenter observational longitudinal study. Consecutive adult cancer patients followed till death during a four-month period and undergoing PS were eligible. Symptom control and level of consciousness were registered every eight hours to death., Results: About 4276 patients were screened, 2894 followed till death, and 531 (18%) underwent PS. PS rate was 15% in HC and 21% in HS (P < 0.001). Principal refractory symptoms were delirium (54%) and dyspnea (45%), respectively, more common in HC (P < 0.001) and HS (P = 0.03). Informed consent was not obtained in 72% of patients but achieved by 96% of families. Midazolam was the most used drug (94% HS vs. 75% HC; P < 0.001) mainly by continuous infusion (74% HC vs. 89% HS; P < 0.001). PS duration was less than 48 hours in 67% of patients. Hydration during PS was less frequent in HC (27% vs. 49%; P < 0.001). In the eight hours before death, consciousness level was unrousable to mild physical stimulation in 81% and symptom control complete in 89% of cases., Conclusion: Our results show feasibility of PS in HC and HS and suggest setting differences in rates, indications, and practice of PS, possibly related to patients' selection or care organization., (Copyright © 2018 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: To develop a convenient and rapid single-kidney CT-GFR technique., Methods: One hundred and twelve patients referred for multiphasic renal CT and 99mTc-DTPA renal dynamic imaging Gates-GFR measurement were prospectively included and randomly divided into two groups of 56 patients each: the training group and the validation group. On the basis of the nephrographic phase images, the fractional renal accumulation (FRA) was calculated and correlated with the Gates-GFR in the training group. From this correlation a formula was derived for single-kidney CT-GFR calculation, which was validated by a paired t test and linear regression analysis with the single-kidney Gates-GFR in the validation group., Results: In the training group, the FRA (x-axis) correlated well (r = 0.95, p < 0.001) with single-kidney Gates-GFR (y-axis), producing a regression equation of y = 1665x + 1.5 for single-kidney CT-GFR calculation. In the validation group, the difference between the methods of single-kidney GFR measurements was 0.38 ± 5.57 mL/min (p = 0.471); the regression line is identical to the diagonal (intercept = 0 and slope = 1) (p = 0.727 and p = 0.473, respectively), with a standard deviation of residuals of 5.56 mL/min., Conclusion: A convenient and rapid single-kidney CT-GFR technique was presented and validated in this investigation., Key Points: • The new CT-GFR method takes about 2.5 min of patient time. • The CT-GFR method demonstrated identical results to the Gates-GFR method. • The CT-GFR method is based on the fractional renal accumulation of iodinated CM. • The CT-GFR method is achieved without additional radiation dose to the patient.

Phosphodiesterases (PDEs) was found to be involved in a variety of cancer pathologies by modulating the degradation of levels of cAMP/cGMP. However, the prognostic significance and biological effect of PDE4a in hepatocellular carcinoma (HCC) have not been understood completely. In the present study, PDE4a expression was detected in a cohort of HCC and matched adjacent liver tissues (n = 210) by immunohistochemistry staining and Western immunoblotting assay, And in vitro experiments were conducted to determine the effect of PDE4a on metastatic capacity of HCC cells. The data here displayed that the majority of HCC patients had higher PDE4a expression in tumor tissues compared to matched adjacent liver tissues and enhanced PDE4a expression in tumor tissues was associated positively with HBV infection, liver cirrhosis, higher serum AFP level, advanced TNM stage, vascular embolus, intrahepatic metastases and portal vein tumor thrombus (PVTT). Survival analyses suggested that higher PDE4a was indicated the poor prognosis of HCCs after liver resection. Ectopic expression of PDE4a in Huh7 cells leaded to significant repression of E-cadherin and up-regulated the expression of N-cadherin and Vimentin, and facilitated migration and invasion abilities. Silencing PDE4a in MHCC97h cells acquired the opposite results. Taken together, PDE4a triggered EMT in HCC cells and acted as a predictive factor candidate and a potential therapeutic target for HCC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Background: Tivantinib (ARQ 197), a selective, oral MET inhibitor, improved overall survival and progression-free survival compared with placebo in a randomised phase 2 study in patients with high MET expression (MET-high) hepatocellular carcinoma previously treated with sorafenib. The aim of this phase 3 study was to confirm the results of the phase 2 trial., Methods: We did a phase 3, randomised, double-blind, placebo-controlled study in 90 centres in Australia, the Americas, Europe, and New Zealand. Eligible patients were 18 years or older and had unresectable, histologically confirmed, hepatocellular carcinoma, an Eastern Cooperative Oncology Group performance status of 0-1, high MET expression (MET-high; staining intensity score ≥2 in ≥50% of tumour cells), Child-Pugh A cirrhosis, and radiographically-confirmed disease progression after receiving sorafenib-containing systemic therapy. We randomly assigned patients (2:1) in block sizes of three using a computer-generated randomisation sequence to receive oral tivantinib (120 mg twice daily) or placebo (twice daily); patients were stratified by vascular invasion, extrahepatic spread, and α-fetoprotein concentrations (≤200 ng/mL or >200 ng/mL). The primary endpoint was overall survival in the intention-to-treat population. Efficacy analyses were by intention to treat and safety analyses were done in all patients who received any amount of study drug. This study is registered with ClinicalTrials.gov, number NCT01755767., Findings: Between Dec 27, 2012, and Dec 10, 2015, 340 patients were randomly assigned to receive tivantinib (n=226) or placebo (n=114). At a median follow-up of 18·1 months (IQR 14·1-23·1), median overall survival was 8·4 months (95% CI 6·8-10·0) in the tivantinib group and 9·1 months (7·3-10·4) in the placebo group (hazard ratio 0·97; 95% CI 0·75-1·25; p=0·81). Grade 3 or worse treatment-emergent adverse events occurred in 125 (56%) of 225 patients in the tivantinib group and in 63 (55%) of 114 patients in the placebo group, with the most common being ascites (16 [7%] patients]), anaemia (11 [5%] patients), abdominal pain (nine [4%] patients), and neutropenia (nine [4%] patients) in the tivantinib group. 50 (22%) of 226 patients in the tivantinib group and 18 (16%) of 114 patients in the placebo group died within 30 days of the last dose of study medication, and general deterioration (eight [4%] patients) and hepatic failure (four [2%] patients) were the most common causes of death in the tivantinib group. Three (1%) of 225 patients in the tivantinib group died from a treatment-related adverse event (one sepsis, one anaemia and acute renal failure, and one acute coronary syndrome)., Interpretation: Tivantinib did not improve overall survival compared with placebo in patients with MET-high advanced hepatocellular carcinoma previously treated with sorafenib. Although this METIV-HCC trial was negative, the study shows the feasibility of doing integral tissue biomarker studies in patients with advanced hepatocellular carcinoma. Additional randomised studies are needed to establish whether MET inhibition could be a potential therapy for some subsets of patients with advanced hepatocellular carcinoma., Funding: ArQule Inc and Daiichi Sankyo (Daiichi Sankyo Group)., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The study characterized the virological patterns and the resistance-associated substitutions (RASs) in patients with failure to IFN-free regimens enrolled in the real-life setting. All 87 consecutive HCV patients with failed IFN-free regimens, observed at the laboratory of the University of Campania, were enrolled. All patients had been treated with DAA regimens according to the HCV genotype, international guidelines, and local availability. Sanger sequencing of NS3, NS5A, and NS5B regions was performed at failure by home-made protocols. Of the 87 patients enrolled, 13 (14.9%) showed a misclassified HCV genotype, probably causing DAA failure, 16 had been treated with a sub-optimal DAA regimen, 19 with a simeprevir-based regimen and 39 with an optimal DAA regimen. A major RAS was identified more frequently in the simeprevir regimen group (68.4%) and in the optimal regimen group (74.4%) than in the sub-optimal regimen group (56.3%). The prevalence of RASs in NS3 was similar in the three groups (30.8-57.9%), that in NS5A higher in the optimal regimen group (71.8%) than in the sub-optimal regimen group (12.5%, P < 0.0001) and in the simeprevir regimen group (31.6%, P < 0.0005), and that in NS5B low in all groups (0-25%). RASs in two or more HCV regions were more frequently identified in the optimal regimen group (46.6%) than in the simeprevir-based regimen group (31.6%) and sub-optimal regimen group (18.7%). In our real-life population the prevalence of RASs was high, especially in NS3 and NS5A and in those treated with suitable DAA regimens., (© 2018 Wiley Periodicals, Inc.)

Improving the emission from rare earth ions doped materials is of great importance to broaden their application in bio-imaging, photovoltaics and temperature sensing. The green emissions of Gd 2 (MoO 4 ) 3 :Er 3+ /Yb 3+ powder upon co-excitation with 980 and 808 nm lasers were investigated in this paper. Distinct enhancement of green emissions was observed compared with single laser excitation. Based on the energy level structure of Er 3+ , the enhancement mechanism was discussed. Moreover, the result of temperature-dependent enhancement revealed that the enhancement factor reached its maximum (2.5) as the sample heated to 120°C, which is due to the competition of two major thermal effects acting in the co-excited up-conversion processes. In addition, the same enhancement of green emissions was also observed in Gd 2 (MoO 4 ) 3 :Er 3+ powder and NaYF 4 :Er 3+ /Yb 3+ powder., (Copyright © 2017 John Wiley & Sons, Ltd.)

The mechanisms underlying neuroinflammation following cerebral ischemia remain unclear. Hydrogen sulfide (H 2 S), a newly identified gasotransmitter, has been reported to regulate inflammation. In the current study, we investigated whether the endogenous H 2 S production pathway contributed to microglia-mediated neuroinflammation following stroke. We used a mouse middle cerebral artery occlusion (MCAO) model and an in vitro cellular model to mimic ischemia-induced microglial neuroinflammation. Expression of the H 2 S synthase cystathionine β-synthase (CBS) and H 2 S synthetic activity were rapidly decreased in the ischemic brain tissue following MCAO. Consistently, when cultured microglia were polarized toward a pro-inflammatory phenotype with conditioned medium collected from neurons that had been subjected to oxygen-glucose deprivation (OGD neuron CM), they displayed reduced CBS expression and H 2 S production. Enhancing H 2 S bioavailability either by overexpressing CBS or by supplementing with exogenous H 2 S donors promoted a shift in microglial polarization from ischemia-induced pro-inflammatory phenotypes toward anti-inflammatory phenotypes. Mechanistically, microglia that were exposed to OGD neuron CM displayed reduced activation of AMP-activated protein kinase (AMPK), which was rescued by overexpressing CBS or by supplementing with H 2 S donors. Moreover, the promoting effects of H 2 S donors on microglial anti-inflammatory polarization were abolished by an AMPK inhibitor or CaMKKβ inhibitor. Our results suggested that reduced CBS-H 2 S-AMPK cascade activity contributed to microglia-mediated neuroinflammation following stroke. Targeting the CBS-H 2 S pathway is a promising therapeutic approach for ischemic stroke., (Copyright © 2017. Published by Elsevier Inc.)

Background: Chemotherapy resistance remains a major challenge in cancer treatment. COX-2 (cyclooxygenase 2) is involved in drug resistance and poor prognosis of many neoplastic diseases or cancers. However, investigations identifying new modulators of COX-2 pathway and searching for new chemicals targeting these valid resistant biomarkers are still greatly needed., Methods: HCT15, HCT-116, HT-29, COLO205, FHC, IMCE, SW480 cell lines were used to detect the expression of YAP and COX-2. Site-directed mutagenesis, luciferase reporter analysis and ChIP assay were used to test whether YAP activated COX-2 transcription through interaction with TEAD binding sites in the promoter of COX-2. Cell line models exhibiting overexpression or knockdown of some genes were generated using transfection agents. Coimmunoprecipitation was used to detect protein mutual interaction. mRNA and protein levels were measured by qRT-PCR and western blot respectively., Results: Here, we reported that both YAP and COX-2 were overexpressed in colorectal cancer cells. YAP increased COX-2 expression at the level of transcription requiring intact TEAD binding sites in the COX-2 promoter. YAP conferred drug resistance through COX-2 and its related effectors such as MCL, MDR, Survivin. GCCSysm-4 (G-4), a YAP and COX-2 inhibitor, effectively inhibited both YAP and COX-2 activation, induced apoptosis and decreased viability in Taxol-resistant cells. Inhibition of YAP and COX-2 acted synergistically and more efficiently reduced the resistance of CRC cells than either of them alone., Conclusions: Our data provide new mechanisms that YAP is a new upstream regulator of COX-2 pathway and plays an important role in conferring resistance in CRC cells. G-4, targeting YAP-COX-2, may be a novel valuable strategy to combat resistance in CRC.