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STAT3 is an oncoprotein which has been shown to contribute to drug resistance in multiple myeloma (MM). Nonetheless, the clinical utility of STAT3 inhibitors in treating MM has been limited, partly related to some of their pharmacologic properties. To overcome these challenges, our group had previously packaged STAT3 inhibitors using a novel formulation of nanoparticles (NP) and found encouraging results. In this study, we aimed to further improve the pharmacologic properties of these NP by decorating them with monoclonal anti-CD38 antibodies. NP loaded with S3I-1757 (a STAT3 inhibitor), labeled as S3I-NP, were generated. S3I-NP decorated with anti-CD38 (labeled as CD38-S3I-NP) were found to have a similar nanoparticular size, drug encapsulation, and loading as S3I-NP. The release of S3I-1757 at 24 h was also similar between the two formulations. Using Cy5.5 labeling of the NP, we found that the decoration of anti-CD38 on these NP significantly increased the cellular uptake by two MM cell lines (p < 0.001). Accordingly, CD38-S3I-NP showed a significantly lower inhibitory concentration at 50% (IC50) compared to S3I-NP in two IL6-stimulated MM cell lines (p < 0.001). In a xenograft mouse model, CD38-S3I-NP significantly reduced the tumor size by 4-fold compared to S3I-NP on day 12 after drug administration (p = 0.006). The efficacy of CD38-S3I-NP in suppressing STAT3 phosphorylation in the xenografts was confirmed by using immunocytochemistry and Western blot analysis. In conclusion, our study suggests that the decoration of anti-CD38 on NP loaded with STAT3 inhibitors can further improve their therapeutic effects against MM.

Background: Aging in men causes a gradual decline in endogenous testosterone levels, which may have detrimental effects on their health status. Testosterone deficiency is thought to promote atherosclerosis by modulating lipid metabolism. Therefore, this study was conducted to evaluate the serum testosterone level and its correlation with lipid profile in men aged ≥60 years old. Methods: All elderly men aged ≥60, residing in Amirkola and participating in a phase of the comprehensive project on "investigating the health status of the elderly in Amirkola" were entered into this descriptive cross-sectional study. After fasting over 12 hours, the venous blood samples were taken. Serum concentration of testosterone was determined using ELISA method. Moreover, HDL-LDL, total cholesterol, triglyceride and fasting blood glucose were measured. Results: The prevalence of hypogonadism was 91.28% among the 792 participants of this study with a cut-off point of 9.72 nmol/L (95% confidence interval, 93.25-89.31) and the prevalence of severe hypogonadism with a cut-off point of 5.2 nmol/L was reported 71.59% (95% confidence interval, 74.73-68.44%). Based on the results, there was no significant statistical correlation between the serum level of testosterone and triglyceride (r=0.03, P=0.34). Furthermore, there was a negative correlation between testosterone and HDL, which was not statistically significant(r=-0.05, P=0.13). No significant statistical correlation was found between testosterone and LDL (P=0.98). There was a negative correlation between testosterone and cholesterol, which was not statistically significant (r=-0.02, P=0.49). Conclusion: According to the study results, 91% of men aged ≥60 years old had hypogonadism, no correlation was found between testosterone and lipid indices. [ABSTRACT FROM AUTHOR]

Objectives: Diverting patients away from the emergency department (ED) has been proposed as a solution for mitigating overcrowding. This systematic review examined the impact of interventions designed to either bypass the ED or direct patients to other alternative care after ED presentation.Methods: Seven electronic databases and the grey literature were searched. Eligible studies included randomised/controlled trials or cohort studies that assessed the effectiveness of pre-hospital or ED-based diversion interventions. Two reviewers independently screened the studies for relevance, inclusion and risk of bias. Pooled statistics were calculated as relative risks (RR) with 95% confidence intervals (CI) using a random effects model.Results: Fifteen studies were included evaluating pre-hospital (n=11) or ED-based (n=4) diversion interventions. The quality of the studies ranged from moderate to low. Patients deemed suitable for diversion among the pre-hospital studies (n=3) ranged from 19.2% to 90.4% and from 19% to 36% in ED-based studies (n=4). Of the eligible patients, the proportion of patients diverted via ED-based diversion tended to be higher (median 85%; IQR 76-93%) compared with pre-hospital diversion (median 40%; IQR 24-57%). Overall, pre-hospital diversion did not decrease the proportion of patients transferred to the ED compared with standard care (RR 0.92; 95% CI 0.80 to 1.06). There was no significant decrease in subsequent ED utilisation among patients diverted via pre-hospital diversion compared with non-diverted patients (RR 1.09; 95% CI 0.99 to 1.21). Of the three pre-hospital studies completing a cost analysis, none found a significant difference in total healthcare costs between diverted and non-diverted patients.Conclusion: There was no conclusive evidence regarding the impact of diversion strategies on ED utilisation and subsequent healthcare utilisation. The overall quality of the research limited the ability of this review to draw definitive conclusions and more research is required prior to widespread implementation. [ABSTRACT FROM AUTHOR]

The pivotal role of datasets in signature verification systems motivates researchers to collect signature samples. Distinct characteristics of Persian signature demand for richer and culture‐dependent offline signature datasets. This study introduces a new and public Persian offline signature dataset, UTSig (University of Tehran Persian Signature), that consists of 8280 images from 115 classes. Each class has 27 genuine signatures, 3 opposite‐hand signatures, and 42 skilled forgeries made by 6 forgers. Compared with the other public datasets, UTSig has more samples, more classes, and more forgers. The authors considered various variables including signing period, writing instrument, signature box size, and number of observable samples for forgers in the data collection procedure. By careful examination of main characteristics of offline signature datasets, they observe that Persian signatures have fewer numbers of branch points and end points. They propose and evaluate four different training and test setups for UTSig. Results of the authors' experiments show that training genuine samples along with opposite‐hand samples and random forgeries can improve the performance in terms of equal error rate and minimum cost of log likelihood ratio. [ABSTRACT FROM AUTHOR]

Carnation (Diantlius caryophyllus L.) is one of the most popular cut flowers in the world with the most economical importance to flower industry. This plant is categorized among cut flowers and is very sensitive to ethylene. A symptom of senescence in carnation is curving of its petals inward. In this sense, with regards to the role of Alcoholic compounds in preventing bio-synthesis of ethylene as a senescence preventing agent and increasing the preservation of cut flowers postharvest, the effect of different treatments including propanol, butanol, and pentanol on carnation 'Nelson' was investigated at 4 levels (0%, 2%, 4%, and 6%) taken randomly. Variables such as vase life, fresh weight, chlorophyll a, petal protein, and ethylene were measured. Findings showed that treatments with 2% and 4% of propanol caused the longest vase life and the least decrease in fresh weight while, in comparison with distilled water, pentanol especially at 4% and 6% had a significantly negative effect on the amount of protein. Except for curing with pentanol, the amount of ethylene increased notably particularly in high densities and propanol at 4% showed the largest amount of chlorophyll a. [ABSTRACT FROM AUTHOR]