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We studied the role of iso-valent heteroatoms replacing Ti 4+ cations in the lattice of two titania polymorphs, rutile (r-) and anatase (a-) by means of first principles calculations. The r-TiO 2 (110) and the a-TiO 2 (101) surfaces have been considered and Ti ions in the bulk, sub-surface, and surface sites have been replaced with Si, Ge, Sn, Pb, Zr, Hf, and Ce ions: surface or sub-surface sites are clearly preferred. Since the dopants have the same number of valence electrons as the replaced Ti atom, they can have only two effects: one is steric, related to the different size of the dopant compared to Ti 4+ ; the other is an orbital effect, due to the energy levels associated to the dopant not present on the pristine surface. Both these effects can modify locally the geometric and electronic structure of the surface, in particular by introducing new states in the band gap. To check the effect of the dopants on the surface reactivity we studied as an example the decomposition of HCOOH which can follow four different paths with desorption of (a) H 2, (b) CO, (c) H 2 O, or (d) CO 2 . The results show the very different behavior of the two titania polymorphs considered, rutile and anatase: rutile is more reactive and more easily reduced than anatase. For specular reasons, the presence of the dopants has in general more pronounced effects on anatase, as they can deeply modify the surface reactivity and the HCOOH decomposition path., (© 2021 IOP Publishing Ltd.)

Gene set analysis has been widely used to gain insight from high-throughput expression studies. Although various tools and methods have been developed for gene set analysis, there is no consensus among researchers regarding best practice(s). Most often, evaluation studies have reported contradictory recommendations of which methods are superior. Therefore, an unbiased quantitative framework for evaluations of gene set analysis methods will be valuable. Such a framework requires gene expression datasets where enrichment status of gene sets is known a priori . In the absence of such gold standard datasets, artificial datasets are commonly used for evaluations of gene set analysis methods; however, they often rely on oversimplifying assumptions that make them biased in favor of or against a given method. In this paper, we propose a quantitative framework for evaluation of gene set analysis methods by synthesizing expression datasets using real data, without relying on oversimplifying or unrealistic assumptions, while preserving complex gene-gene correlations and retaining the distribution of expression values. The utility of the quantitative approach is shown by evaluating ten widely used gene set analysis methods. An implementation of the proposed method is publicly available. We suggest using Silver to evaluate existing and new gene set analysis methods. Evaluation using Silver provides a better understanding of current methods and can aid in the development of gene set analysis methods to achieve higher specificity without sacrificing sensitivity.

Nowadays, radiation grafting polymer adsorbents have been widely developed due to their advantages, such as low operating cost, high efficiency. In this research, glycidyl methacrylate monomers were grafted on polypropylene polymer fibers by simultaneous irradiation of gamma-ray with a dose of 20 kGy. The grafted polymer was then modified using different amino groups and tested for adsorption of cobalt ions in an aqueous solution. Finally, the modified polymer adsorbent with a high efficiency for cobalt ions adsorption was synthesized and tested. Different modes of cobalt ions adsorption were tested in other adsorption conditions, including adsorption contact time, pH, different amounts of adsorbent mass, and different concentrations of cobalt ions solution. The adsorbent structure was characterized with FT-IR, XRD, TG and SEM techniques and illustrated having an efficient grafting percentage and adsorption capability for cobalt removing by batch experiments. The optimum conditions were obtained by a central composite design: adsorbent mass = 0.07 g, initial concentration = 40 mg/L, time = 182 min, and pH = 4.5 with ethylenediamine as a modified monomer and high amination percentage. Kinetics and equilibrium isotherms observation described that the experimental data followed pseudo-second-order and Langmuir models, respectively. The maximum adsorption capacity from Langmuir isotherm capacity is obtained equal to 68.02 mg/g., (© 2021. The Author(s).)

A number of studies have demonstrated that patients with autoimmune disease have lower levels of vitamin D prompting speculation that vitamin D might suppress inflammation and immune responses in children with juvenile idiopathic arthritis (JIA).  The objective of this study was to compare vitamin D levels in children with JIA at disease onset with healthy children. We hypothesized that children and adolescents with JIA have lower vitamin D levels than healthy children and adolescents. Data from a Canadian cohort of children with new-onset JIA (n= 164, data collection 2007-2012) were compared to Canadian Health Measures Survey (CHMS) data (n=4027, data collection 2007-2011). We compared 25-hydroxy vitamin D (25(OH)D) concentrations with measures of inflammation, vitamin D supplement use, milk intake, and season of birth. Mean 25(OH)D level was significantly higher in patients with JIA (79 ± 3.1 nmol/L) than in healthy controls (68 ± 1.8 nmol/L P <.05). Patients with JIA more often used vitamin D containing supplements (50% vs. 7%; P <.05). The prevalence of 25(OH)D deficiency (<30 nmol/L) was 6% for both groups. Children with JIA with 25(OH)D deficiency or insufficiency (<50 nmol/L) had higher C-reactive protein levels. Children with JIA were more often born in the fall and winter compared to healthy children. In contrast to earlier studies, we found vitamin D levels in Canadian children with JIA were higher compared to healthy children and associated with more frequent use of vitamin D supplements. Among children with JIA, low vitamin D levels were associated with indicators of greater inflammation., (Copyright © 2021. Published by Elsevier Inc.)

Current radiomic studies of head and neck squamous cell carcinomas (HNSCC) are typically based on datasets combining tumors from different locations, assuming that the radiomic features are similar based on histopathologic characteristics. However, molecular pathogenesis and treatment in HNSCC substantially vary across different tumor sites. It is not known if a statistical difference exists between radiomic features from different tumor sites and how they affect machine learning model performance in endpoint prediction. To answer these questions, we extracted radiomic features from contrast-enhanced neck computed tomography scans (CTs) of 605 patients with HNSCC originating from the oral cavity, oropharynx, and hypopharynx/larynx. The difference in radiomic features of tumors from these sites was assessed using statistical analyses and Random Forest classifiers on the radiomic features with 10-fold cross-validation to predict tumor sites, nodal metastasis, and HPV status. We found statistically significant differences ( p -value ≤ 0.05) between the radiomic features of HNSCC depending on tumor location. We also observed that differences in quantitative features among HNSCC from different locations impact the performance of machine learning models. This suggests that radiomic features may reveal biologic heterogeneity complementary to current gold standard histopathologic evaluation. We recommend considering tumor site in radiomic studies of HNSCC.

Bioethanol produced by fermentative microorganisms is regarded as an alternative to fossil fuel. Bioethanol to be used as a viable energy source must be produced cost-effectively by removing expense-intensive steps such as the enzymatic hydrolysis of substrate. Consolidated bioprocessing (CBP) is believed to be a practical solution combining saccharification and fermentation in a single step catalyzed by a microorganism. Bacillus subtills with innate ability to grow on a diversity of carbohydrates seems promising for affordable CBP bioethanol production using renewable plant biomass and wastes. In this study, the genes encoding alcohol dehydrogenase from Z. mobilis (adh Z ) and S. cerevisiae (adh S ) were each used with Z. mobilis pyruvate decarboxylase gene (pdc Z ) to create ethanologenic operons in a lactate-deficient (Δldh) B. subtilis resulting in NZ and NZS strains, respectively. The S. cerevisiae adh S caused significantly more ethanol production by NZS and therefore was used to make two other operons including one with double copies of both pdc Z and adh S and the other with a single pdc Z but double adh S genes expressed in N(ZS)2 and NZS2 strains, respectively. In addition, two fusion genes were constructed with pdc Z and adh S in alternate orientations and used for ethanol production by the harboring strains namely NZ:S and NS:Z, respectively. While the increase of gene dosage was not associated with elevated carbon flow for ethanol production, the fusion gene adh S :pdc Z resulted in a more than two times increase of productivity by strain NS:Z as compared with NZS during 48 h fermentation. The CBP ethanol production by NZS and NS:Z using potatoes resulted in 16.3 g/L and 21.5 g/L ethanol during 96 h fermentation, respectively. For the first time in this study, B. subtilis was successfully used for CBP ethanol production with S. cerevisiae alcohol dehydrogenase. The results of the study provide insights on the potentials of B. subtilis for affordable bioethanol production from inexpensive plant biomass and wastes. However, the potentials need to be improved by metabolic and process engineering for higher yields of ethanol production and plant biomass utilization.

Mucin 1 (MUC1) is a large, transmembrane mucin glycoprotein overexpressed in most adenocarcinomas and plays an important role in tumor progression. Regarding its cellular distribution, biochemical features, and function, tumor-related MUC1 varies from the MUC1 expressed in normal cells. Therefore, targeting MUC1 for cancer immunotherapy and imaging can exploit the difference between cancerous and normal cells. Radiopharmaceuticals have a potential use as carriers for the delivery of radionuclides to tumors for a diagnostic imaging and radiotherapy. Several radiolabeled targeting molecules like peptides, antibodies, and aptamers have been efficiently demonstrated in detecting and treating cancer by targeting MUC1. This review provides a brief overview of the current status of developments and applications of MUC1-targeted radiopharmaceuticals in cancer imaging and therapy.

Background and Aim: To conduct a systematic literature review and synthesize data from all epidemiological studies investigating the association between diabetes and migraine in adults., Method and Material: Electronic databases, including Web of Science, PubMed and Scopus in addition to Google Scholar search engine were systematically searched up to Jun 2020 to identify studies reporting the diabetes-migraine association., Results: A total of 15 studies were selected which were published from 2012 to 2019. Five out of 15 studies assessed the presence of migraine in diabetic subjects, while nine studies assessed the presence of diabetes in migraine subjects. The cohort study reported a hazard ratio for diabetes of 1.06 (95% confidence interval (CI): 0.91-1.24) for women with migraine with aura, 1.01 (95% CI: 0.89-1.16) for women without aura, and 1.13 (95% CI: 0.98-1.3) for women with a migraine history, compared with women with no history of migraine. Due to the high degree of heterogeneity, and the lack of statistical estimates of the association in several of the reviewed studies, meta-analysis of the available data was not possible., Conclusion: This study is the first review to examine the association between diabetes and migraine. Further longitudinal studies are required to clarify the migraine-diabetes association. There is also a clear need for more studies with larger sample sizes and similar methodologies in order to provide necessary information to conduct a meta-analysis., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2021 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to determine the relationship between dietary total antioxidant capacity (dTAC) and risk of breast cancer among Iranian women., Design: In this hospital-based case-control study, dietary intake of participants was collected using a 168-item validated FFQ. Dietary TAC was assessed using FRAP assay considering. Logistic regression was used to obtain ORs for breast cancer across quartiles of dTAC., Setting: Cancer Institute, Iran., Participants: We included 412 women with pathologically confirmed breast cancer and 456 apparently healthy controls., Results: Mean dTAC was 11·3 ± 5·8 for cases and 12·1 ± 7·9 for controls. A trend towards significant inverse association was seen between dTAC and odds of breast cancer in the whole population; such that after controlling for several potential confounders, individuals in the highest quartile of dTAC were 0·39 times less likely to have breast cancer than those in the lowest quartile (0·61; 95 % CI: 0·38, 0·99, P < 0·05). In the stratified analysis by menopausal status, we found that postmenopausal women with the greatest dTAC had lower odds for breast cancer, compared with those with the lowest dTAC (0·47; 95 % CI: 0·24, 0·93, P < 0·05). This association strengthened after additional adjustment for BMI (0·28; 95 % CI: 0·11, 0·72, P < 0·05). No significant association was seen between dTAC and odds of breast cancer in premenopausal women., Conclusions: We found that dietary TAC was inversely associated with risk of breast cancer, in particular among postmenopausal women. Prospective cohort studies are needed to confirm these findings.

Background: Gene co-expression networks (GCNs) are not easily comparable due to their complex structure. In this paper, we propose a tool, Juxtapose, together with similarity measures that can be utilized for comparative transcriptomics between a set of organisms. While we focus on its application to comparing co-expression networks across species in evolutionary studies, Juxtapose is also generalizable to co-expression network comparisons across tissues or conditions within the same species., Methods: A word embedding strategy commonly used in natural language processing was utilized in order to generate gene embeddings based on walks made throughout the GCNs. Juxtapose was evaluated based on its ability to embed the nodes of synthetic structures in the networks consistently while also generating biologically informative results. Evaluation of the techniques proposed in this research utilized RNA-seq datasets from GTEx, a multi-species experiment of prefrontal cortex samples from the Gene Expression Omnibus, as well as synthesized datasets. Biological evaluation was performed using gene set enrichment analysis and known gene relationships in literature., Results: We show that Juxtapose is capable of globally aligning synthesized networks as well as identifying areas that are conserved in real gene co-expression networks without reliance on external biological information. Furthermore, output from a matching algorithm that uses cosine distance between GCN embeddings is shown to be an informative measure of similarity that reflects the amount of topological similarity between networks., Conclusions: Juxtapose can be used to align GCNs without relying on known biological similarities and enables post-hoc analyses using biological parameters, such as orthology of genes, or conserved or variable pathways., Availability: A development version of the software used in this paper is available at https://github.com/klovens/juxtapose.

We present an extremely rare report on gastric inlet obstruction due to giant abdominal aortic aneurysm. Despite the rare occurrence of this manifestation, it should be considered in the differential diagnosis of gastric inlet obstructions., Competing Interests: None declared., (© 2021 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

Introduction: COVID-19 has affected the pattern of referral to medical centers and quarantine against COVID-19 might delay referral and management of surgical emergencies. This study aimed to compare the pooled event rate of pediatric perforated appendicitis before and during the COVID-19 pandemic., Methods: This was a systematic review and meta-analysis study based on the PRISMA guidelines. Scopus, Web of Sciences, and PubMed databases were searched for studies reporting the rate of perforated appendicitis based on the post-appendectomy observations or imaging methods. The Egger bias test and funnel plot were used to detect and depict publication bias. Statistical analysis was performed in Comprehensive Meta-analysis package version 3., Results: Twelve studies were eligible for inclusion in our study. The pooled prevalence of pediatric perforated appendicitis in the pre-COVID era was 28.5% (CI95%: 28.3 to 28.7%) with a heterogeneity of 99%. In the COVID era, the event rate proportion was 39.4% (CI95%: 36.6 to 42.3%) with a heterogeneity of 99%. There was a significant difference in the subgroup analysis within the pre-COVID and COVID era (P<0.001), showing a higher perforation rate in the COVID era., Conclusion: Our study showed that during the COVID-19 pandemic, the rate of perforated appendicitis has significantly increased in comparison to before the COVID-19 pandemic., Competing Interests: The authors have declared that no competing interests exist.

Some fungal species of the genera Aspergillus, Penicillium, and Fusarium secretes toxic metabolites known as mycotoxins, have become a global concern that is toxic to different species of animals and humans. Biological mycotoxins detoxification has been studied by researchers around the world as a new strategy for mycotoxin removal. Bacteria, fungi, yeast, molds, and protozoa are the main living organisms appropriate for the mycotoxin detoxification. Enzymatic and degradation sorptions are the main mechanisms involved in microbiological detoxification of mycotoxins. Regardless of the method used, proper management tools that consist of before-harvest prevention and after-harvest detoxification are required. Here, in this review, we focus on the microbiological detoxification and mechanisms involved in the decontamination of mycotoxins., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: L-Carnitine is a cardioprotective agent which balances metabolism by promoting mitochondrial β-oxidation and facilitating transportation of long chain fatty acids into the mitochondrial matrix. It has been shown that L-Carnitine level in plasma and tissue is lower in hemodialysis patients and they may lose the benefits of this substance. The aim of this trial was to evaluate the effects of L-Carnitine supplementation on cardiorespiratory Function in hemodialysis patients through ergospirometry., Methods: The current study was conducted on 46 chronic hemodialysis patients. The patients were divided into two groups. In both groups ergospirometry parameters (VE Max, VO2-Max and VCO2 Max, AT, VE/VCO2 Slope) were recorded for a 3-month period of time. During this period, one group received L-Carnitine at doses of 2 g/d orally and the other group received only placebo. After three months, all of the mentioned parameters reevaluated and statistical analysis was done., Results: Only CRP value was different between two group and in placebo group increased significantly after 3 months (P < .05). No significant difference was detected in Cardio-respiratory factors. In terms of ergospirometry, PET-CO2 was the only parameter which was significantly increased in the treatment group but decreased in placebo group (P < .05)., Conclusion: Significant differences between our groups showed that L-Carnitine could help hemodialysis patients with cardiopulmonary problems to suffer lower rate of inflammation and poor life quality as shown at least in comparison of the two factors including CRP and PETCO2 at rest.

Background: The Gail model is the most well-known tool for breast cancer risk assessment worldwide. Although it was validated in various Western populations, inconsistent results were reported from Asian populations. We used data from a large case-control study and evaluated the discriminatory accuracy of the Gail model for breast cancer risk assessment among the Iranian female population., Methods: We used data from 942 breast cancer patients and 975 healthy controls at the Cancer Institute of Iran, Tehran, Iran, in 2016. We refitted the Gail model to our case-control data (the IR-Gail model). We compared the discriminatory power of the IR-Gail with the original Gail model, using ROC curve analyses and estimation of the area under the ROC curve (AUC)., Results: Except for the history of biopsies that showed an extremely high relative risk (OR=9.1), the observed ORs were similar to the estimates observed in Gail's study. Incidence rates of breast cancer were extremely lower in Iran than in the USA, leading to a lower average absolute risk among the Iranian population (2.78, ±SD 2.45). The AUC was significantly improved after refitting the model, but it remained modest (0.636 vs. 0.627, ΔAUC = 0.009, bootstrapped P =0.008). We reported that the cut-point of 1.67 suggested in the Gail study did not discriminate between breast cancer patients and controls among the Iranian female population., Conclusion: Although the coefficients from the local study improved the discriminatory accuracy of the model, it remained modest. Cohort studies are warranted to evaluate the validity of the model for Iranian women., Competing Interests: Conflict of interest The authors declare that there is no conflict of interest., (Copyright © 2020 Rostami et al. Published by Tehran University of Medical Sciences.)

The head and neck (HN) consists of a large number of vital anatomic structures within a compact area. Imaging plays a central role in the diagnosis and management of major disorders affecting the HN. This article reviews the recent applications of machine learning (ML) in HN imaging with a focus on deep learning approaches. It categorizes ML applications in HN imaging into deep learning and traditional ML applications and provides examples of each category. It also discusses the main challenges facing the successful deployment of ML-based applications in the clinical setting and provides suggestions for addressing these challenges., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The extensive body of research and advances in machine learning (ML) and the availability of a large volume of patient data make ML a powerful tool for producing models with the potential for widespread deployment in clinical settings. This article provides an overview of the classic supervised and unsupervised ML methods as well as fundamental concepts required for understanding how to develop generalizable and high-performing ML applications. It also describes the important steps for developing a ML model and how decisions made in these steps affect model performance and ability to generalize., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

The aim of this study was to prepare radiolabeled peptide-based agents for imaging of colon cancer. According to the incorporation of HYNIC for radiolabeling with technetium-99m, two analogs were designed and compared: an antitumor-antibody-derived peptide based on the EPPT sequence and a novel retro-inverso peptidomimetic derivative D (TPPE) structurally modified by replacing the L-amino acids with D-amino acids and reversing the primary amino acid sequence of EPPT. The HYNIC-conjugated peptides were labeled with 99m Tc using tricine/EDDA coligand with more than 98% radiochemical yield and showed high metabolic stability. Kd values of 41.77 ± 7.34 nM and 37.33 ± 8.37 nM for 99m Tc-HYNIC-EPPT and 99m Tc-HYNIC- D (TPPE) confirmed high affinity of both peptides for cell surface antigen MUC1. These radiotracers demonstrated no significant differences in the cellular uptake and internalization value, but the biodistribution profile of 99m Tc-HYNIC- D (TPPE) was more favorable than that of 99m Tc-HYNIC-EPPT as a result of better tumor-to-non-target ratios for the examined tissues and organs. HT29 tumors were visualized more clearly in scintigraphic images with 99m Tc-HYNIC- D (TPPE) in comparison with 99m Tc-HYNIC-EPPT. The results showed the retro-inverso analog to be a more promising radiotracer as a probe for in vivo targeting of HT-29 tumors than the parent peptide., (© 2020 John Wiley & Sons A/S.)

This article reviews the history of artificial intelligence and introduces the reader to major events that prompted interest in the field, as well as pitfalls and challenges that have slowed its development. The purpose of this article is to provide a high-level historical perspective on the development of the field over the past decades, highlighting the potential of the field for transforming health care, but also the importance of setting realistic expectations for artificial intelligence applications to avoid repeating historical cyclical trends and a third "artificial intelligence winter.", (Copyright © 2020 Elsevier Inc. All rights reserved.)

The deployment of machine learning (ML) models in the health care domain can increase the speed and accuracy of diagnosis and improve treatment planning and patient care. Translating academic research to applications that are deployable in clinical settings requires the ability to generalize and high reproducibility, which are contingent on a rigorous and sound methodology for the development and evaluation of ML models. This article describes the fundamental concepts and processes for ML model evaluation and highlights common workflows. It concludes with a discussion of the requirements for the deployment of ML models in clinical settings., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Deep learning has contributed to solving complex problems in science and engineering. This article provides the fundamental background required to understand and develop deep learning models for medical imaging applications. The authors review the main deep learning architectures such as multilayer perceptron, convolutional neural networks, autoencoders, recurrent neural networks, and generative adversarial neural networks. They also discuss the strategies for training deep learning models when the available datasets are imbalanced or of limited size and conclude with a discussion of the obstacles and challenges hindering the deployment of deep learning solutions in clinical settings., (Copyright © 2020 Elsevier Inc. All rights reserved.)

We characterize a high-capacity cation exchange membrane (CEM) synthesized from an aqueous poly(vinyl alcohol) (PVA) solution and varying amounts of a water-soluble ionic monomer, sodium styrenesulfonate. Highly hydrophilic but water-insoluble transparent polymers with a range of ion exchange capacities (IECs) can be made; at the high end, the ion exchange capacities (IEC) is >2× that of the benchmark CEM, Nafion. The water uptake of the polymer (as moles of water/mole H + ) is 5-10× greater than that of Nafion. Except at the highest IECs (where steeply increasing water sorption and resultant swelling outpaces IEC increase), the specific conductance increases with increasing IEC while the conductance anisotropy decreases. The material withstands repeated regeneration cycles and hour-long boiling in water or alcohols. The aqueous prepolymer mixture can be cast around a fine wire acting as a mandrel. Fabrication of an ion exchanger microchannel, capable of withstanding at least 300 psi, is demonstrated. We also discuss entirely novel considerations on ab initio limits of conductance of ion exchange membranes.

Background: Antimicrobial resistance of Helicobacter pylori can result in eradication failure. Metadata on the antimicrobial resistance of H pylori in Iran could help to formulate H pylori eradication strategies in Iran., Methods: A systematic review was performed after searching in MEDLINE, Scopus, Embase, Web of Science, and the Cochrane Library. A meta-analysis was performed, and a comparison of the rates between children and adults; time periods (1999-2010, 2011-2016, 2017-2019); and the methods used was carried out., Results: A total of 66 studies investigating 5936 H pylori isolates were analyzed. The weighted pooled resistance (WPR) rates were as follows: clarithromycin 21% (95% CI 16-26), metronidazole 62% (95% 57-67), clarithromycin in combination with metronidazole 16% (95% CI 10-23), ciprofloxacin 24% (95% CI 15-33), levofloxacin 18% (95% CI 9-30), erythromycin 29% (95% CI 12-50), furazolidone 13% (95% CI 4-27), tetracycline 8% (95% CI 5-13), and amoxicillin 15% (95% CI 9-22). During the three time periods, there was an increased resistance to amoxicillin, clarithromycin, ciprofloxacin, furazolidone, and tetracycline (P ˂ .05). Furazolidone and a clarithromycin/metronidazole combination had the higher resistance rates in children (P ˂ .05)., Conclusion: An increasing rate of resistance to amoxicillin, clarithromycin, ciprofloxacin, furazolidone, and tetracycline in Iranian H pylori isolates was identified. In children, the resistance to furazolidone and a combination of clarithromycin and metronidazole is higher compared to adults. As a stable, high resistance to metronidazole was found in children and adults in all Iranian provinces, we suggest that metronidazole should not be included in the Iranian H pylori eradication scheme., (© 2020 John Wiley & Sons Ltd.)

Human cytomegalovirus (HCMV), as a ubiquitous and opportunistic virus, is a matter for consideration in broad-spectrum diseases, specifically in immunocompromised individuals. In recent decades, many studies that have evaluated the role of HCMV in inflammation and malignancies, especially in high-grade gliomas, have reported inconsistent results. Thus, this study was conducted to analyze 97 primary gliomas for human CMV UL83 gene and protein through TaqMan real-time polymerase chain reaction and immunohistochemistry, respectively. The results were positive for the UL83 gene and pp65 protein in 71% and 24% of samples, respectively. The frequency of HCMV was significantly higher in glioblastomas than other glioma grades (P < .01 and P < .05 for the UL83 gene and protein, respectively). In addition, the association between the prevalence of HCMV and aging strengthened the virus reactivation hypothesis in gliomas. In conclusion, a high frequency of HCMV infection was found in gliomas that correlated with tumor aggressiveness and age. This study recommends a thorough investigation to determine HCMV infection in gliomas to improve the existing knowledge of its role in glial tumors, its prognostic value, and possible efficient antiviral target therapy., (© 2020 Wiley Periodicals, Inc.)

Prostate cancer is a serious threat to men's health, so it is necessary to develop the techniques for early detection of this malignancy. Radiolabeled peptides are the useful tools for diagnosis of prostate cancer. In this research, we designed a new HYNIC-conjugated GnRH analogue and labeled it by 99m Tc with tricine/EDDA as coligands. We used aminohexanoic acid (Ahx) as a hydrocarbon linker to generate 99m Tc-(tricine/EDDA)-HYNIC-Ahx-[DLys 6 ]GnRH. The radiopeptide exhibited high radiochemical purity and stability in solution and serum. Two human prostate cancer cell lines LN-CaP and DU-145 were used for cellular experiments. The binding specificity and affinity of radiopeptide for LN-CaP were superior to DU-145 cells. The K d values for LN-CaP and DU-145 cells were 41.91 ± 7.03 nM and 55.96 ± 10.56 nM, respectively. High kidney uptake proved that the main excretion route of radiopeptide was through the urinary system. The tumor/muscle ratio of 99m Tc-HYNIC-Ahx-[DLys 6 ]GnRH was 4.14 at 1 hr p.i. that decreased to 2.41 at 4 hr p.i. in LN-CaP tumor-xenografted nude mice. The blocking experiment revealed that the tumor uptake was receptor-mediated. The lesion was visualized clearly using 99m Tc-[DLys 6 ]GnRH at 1 hr p.i. Accordingly, this research highlights the capability of 99m Tc-(tricine/EDDA)-HYNIC-Ahx-[DLys 6 ]GnRH peptide as a promising agent for GnRHR-expressing tumor imaging., (© 2020 John Wiley & Sons A/S.)

Background: The incidence rate of breast cancer (BC) is increasing in low- and middle-income countries (LMICs), including Iran. We investigated the association between BC risk and physical activity (PA), body mass index (BMI), and reproductive history among Iranian women., Methods: We conducted a large hospital-based case-control study and compared 958 BC cases with 967 controls at the Cancer Institute of Iran during 2011-2016. We used multiple logistic regression models and adjusted for potential confounders to estimate odds ratios (ORs) and 95% confidence intervals (95%CIs) for the associations between BC and different risk factors, including low physical activity., Results: Women with high levels of physical activity had a lower risk of BC compared to those who were inactive (OR = 0.55, 95%CI: 0.41, 0.75). In premenopausal women, the association was observed only in normal-weight women (OR = 0.31, 95%CI: 0.13, 0.75), while it was limited to obese women in the postmenopausal group (OR = 0.29, 95%CI: 0.12, 0.66). We found a high risk of postmenopausal BC among overweight (OR = 1.69; 95%CI: 1.01, 2.81) and obese women (OR = 1.9; 95%CI: 1.14, 3.14) compared to women with a normal BMI. We observed an inverse association among postmenopausal women who had between three and five children (OR = 0.31, 95%CI 0.14, 0.64) and more than six children (OR = 0.21, 95%CI 0.12, 0.42) compared to nulliparous women., Conclusions: Low levels of physical activity, low parity, and being overweight or obese were major risk factors for BC. For the first time, we report a strong association between physical activity and BC risk in Iranian women., (Copyright © 2020. Published by Elsevier Ltd.)

Multiple applications of dual energy computed tomography (DECT) have been described for the evaluation of disorders in the head and neck, especially in oncology. We review the body of evidence suggesting advantages of DECT for the evaluation of the neck compared with conventional single energy computed tomography scans, but the full potential of DECT is still to be realized. There is early evidence suggesting significant advantages of DECT for the extraction of quantitative biomarkers using radiomics and machine learning, representing a new horizon that may enable this technology to reach its full potential., Competing Interests: Disclosure R. Forghani is a clinical research scholar (chercheur-boursier clinicien) supported by the FRQS (Fonds de recherche en santé du Québec). R. Forghani has acted as a consultant and speaker and has a research agreement and research support from GE Healthcare. R. Forghani is also founder and stockholder of 4intelligent Inc., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: The APT EDB is an aptide specific to the extra domain B (EDB) of fibronectin with high affinity for EDB, which is expressed in malignant tumors including brain cancer (U87MG) and colorectal cancer (HT-29). Aim of this study was to evaluate the [ 99m Tc] Tc-APT EDB potential as an imaging probe for colorectal cancer., Methods: Radiochemical purity was evaluated by HPLC and radio-isotope TLC scanner. Blocking study for specific binding assay and affinity calculation (K d ) on HT-29 cell lines were also carried out. Planar imaging and bio-distribution studies were performed in HT-29 tumor-bearing mice., Results: The APT EDB was efficiently labeled with technetium-99m in high radiochemical yield (up to 97%). Cellular binding study demonstrated specific binding of the [ 99m Tc] Tc-APT EDB in cultured HT-29 cells. The K d value was found to be 40.46 ± 13.39 nM. The tumor-to-muscle ratio was ~ 1.5 in ex vivo bio-distribution study at 1 h after injection. Planar imaging study showed higher activity accumulation in EDB expressing HT-29 tumor relative to muscle (used as control) (~ 1.7) at 1 h., Conclusions: Although more studies are required to find out the full potential of this radio-ligand as an imaging probe, the present results nevertheless provide useful information about [ 99m Tc] Tc-APT EDB , which might be beneficial in design and development of new [ 99m Tc] Tc-APT EDB for efficient targeting of tumor in vivo.

Gene set analysis methods are widely used to provide insight into high-throughput gene expression data. There are many gene set analysis methods available. These methods rely on various assumptions and have different requirements, strengths and weaknesses. In this paper, we classify gene set analysis methods based on their components, describe the underlying requirements and assumptions for each class, and provide directions for future research in developing and evaluating gene set analysis methods., (Copyright © 2020 Maleki, Ovens, Hogan and Kusalik.)

Molecular imaging techniques are increasingly being used in localization, staging and therapy control of cancer. Due to their unique target specificity for the endogenous receptors, radiopeptides have been used widely for the development of radiopharmaceuticals for targeted tumor imaging in nuclear oncology. It is necessary to modify radiolabeled peptides in order to achieve more effective agents. Structural modifications of amino acid chains have significant effect on the metabolic stability, biological activity and efficiency of peptide conjugates that are currently applied as imaging tracers. There are several ways to modify the peptide chain but the most common strategies include amino acid substitutions, cyclization and multimerization. In this review, we have focused on studies involving these kind of modifications on amino acid sequences of radiolabeled peptides and we have provided an overview of the effects of these chemical modifications on the in vitro and in vivo properties of these radioconjugates and their potential as SPECT (Single photon emission computed tomography) and PET (positron emission tomography) imaging agents., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Blood transfusion is a life-saving procedure; millions of lives are saved each year. However, blood transfusions are associated with certain risks that can lead to adverse consequences. This study aimed to survey the prevalence and trend of hepatitis B virus (HBV), hepatitis C virus (HCV), and Human immunodeficiency virus (HIV) among blood donors of Fars province, Iran (2006-2018)., Methods: This retrospective cross-sectional study was conducted by reviewing the records of the blood transfusion organization of Fars province. A total of 1952478 blood units were screened for transfusion-transmitted infections (TTIs). Then, data were entered into SPSS software (Negare. version 25). Chi-square test was used to compare the sof TTIs among blood donors. Chisquare test for trend was used to analyze the variations in trends of TTIs during this period. Finally, p-values less than 0.05 were considered statistically significant. GraphPad Prism software was used for the depiction of the graphs., Results: Among the 1952478 blood donations within the 13-years, 4479(0.229 %) of donors were HBsAg, HCV Ab, and HIV Ag-Ab positive. The seroprevalence of HBV, HCV, and HIV was 2684(0.137%), 1703(0.087 %), and 92(0.0047%), respectively., Conclusion: The current study showed that the overall prevalence of TTIs among blood donors was low and had a descending trend over the years of study., (© 2020 Mojtaba A., et al.)

TGFαL3-SEB is a new synthetic fusion protein produced by the combination of the third loop of transforming growth factor with staphylococcal enterotoxin type B. In the current study, the anti-tumor effects of TGFαL3-SEB were evaluated against SKOV3 cells, which highly expressed the epidermal growth factor receptor (EGFR). Our findings showed that incubation of SKOV3 cells with 75, 100 and 150 μg/ml of TGFαL3-SEB significantly reduces the proliferation rate in a concentration-dependent manner (P < 0.05) and its IC50 value was 110 μg/ml. Caspase-3 activity was increased from 100% for control cells to 109, 144, and 169% for 75, 100 and 150 μg/ml of TGFαL3-SEB treatment, respectively. Caspase-9 activity and bax/bcl-2 ratio were also confirmed the apoptosis induction ability of TGFαL3-SEB (P < 0.001). Flow cytometry examination also showed that apoptosis was induced and the number of apoptotic cells was increased from 8.2% in un-treated cells to 20.9, 50, and 90% in response to 75, 100 and 150 μg/ml of TGFαL3-SEB fusion protein in a concentration-dependent manner (P < 0.05). The mRNA expression level of VEGF was also reduced to 0.89, 0.69, and 0.60, respectively in response to 75, 100 and 150 μg/ml of TGFαL3-SEB fusion protein exposure, respectively (P < 0.5). In summary, the findings of our study uncovered that TGFαL3-SEB fusion protein induced apoptosis and reduced angiogenesis in SKOV3 ovarian cancer cells in a concentration-dependent manner. This protein has the potential to act against EGFR expressing malignant cells to serve as a pro-apoptotic and angiogenesis blocker agents; however, further studies are needed to confirm its ability., (Copyright © 2020. Published by Elsevier B.V.)

Background: Drug abuse is a major issue and one of the main causes of health, psychological, and social problems. Studies have shown the effectiveness of narrative therapy in reducing psychological symptoms of addiction. The present study aimed to assess the effectiveness of group narrative therapy on depression, quality of life (QoL), and anxiety among people with amphetamine addiction in Kermanshah, Iran., Methods: A randomized clinical trial was conducted during 2015-2016 among patients (n=26) with amphetamine addiction in Kermanshah, Iran. The participants were randomly divided into intervention and control groups. The intervention group followed 10 sessions of narrative therapy, whereas the control group received routine psychiatric care. The data collection tools included a demographic data form, Beck depression inventory-II, QoL questionnaire, and Beck anxiety inventory. The data were analyzed using SPSS software (version 22.0). P&lt;0.05 was considered statistically significant., Results: There was a statistically significant reduction in depression and anxiety scores between the pre- and post-intervention stages (P&lt;0.001) in the intervention group. However, their QoL was unaffected by the therapy (P=0.487). These variables did not show a significant change in the control group., Conclusion: Group narrative therapy reduced the level of depression and anxiety in patients with amphetamine addiction. However, their QoL was unaffected by the therapy. Trial Registration Number: IRCT2016010425442N., (Copyright: © Iranian Journal of Medical Sciences.)

Background: The hypothalamic-pituitary-adrenal (HPA) axis dysregulation which was found to have an important role in the pathophysiology of depression, suicide, and substance dependence, may be influenced by childhood maltreatment (CM). The present study aimed to investigate the relationship between CM and cortisol changes in methamphetamine-dependent individuals., Methods: In a cross-sectional study, methamphetamine-dependent individuals (n = =195) with or without both comorbid major depressive disorder (MDD) and a history of suicide attempts were selected and completed the Childhood Trauma Questionnaire-Short Form (CTQ-SF), the Beck Scale for Suicide Ideation (BSSI), and the Beck Depression Inventory-II (BDI-II). To assess cortisol levels, saliva samples were collected at six time intervals for two consecutive days., Results: A history of CM significantly predicted wake-up cortisol level, cortisol awakening response (CAR), and diurnal cortisol slope. Methamphetamine-dependent individuals with both MDD and lifetime suicide attempts had higher CM and higher cortisol levels with a blunted diurnal cortisol slope than individuals who were merely methamphetamine-dependent. Individuals with high CM showed higher cortisol levels with a blunted diurnal slope than those with low or without CM., Limitations: Cross-sectional data and use of self-report scales, especially retrospective measurements (e.g., the CTQ-SF), were important limitations of this study., Conclusion: Findings suggest that methamphetamine-dependent individuals with adverse psychological factors such as CM, MDD, and suicide attempts may show dysregulation in biological factors including cortisol level. In addition, CM and its effects on cortisol in the HPA axis may emerge as important factors regarding psychopathological use of methamphetamine., Competing Interests: Declaration of Competing Interest No conflict declared, (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Arginine-glycine-aspartic acid (RGD) peptide with its specific binding affinity to integrin αvβ3, is widely investigated for the development of molecular imaging probes for diagnosis of αvβ3-positive tumors. The aim of this work was to evaluate the ability of Tc- HYNIC-D(RGD), a novel retro-inverso peptidomimetic derivative for U87MG tumor (αvβ3-positive) imaging., Methods: HYNIC-D(RGD) labeled with Tc using tricine/EDDA as an exchange coligands. Single-photon emission computed tomography imaging and biodistribution study were performed in nude mice bearing U87MG xenograft tumor., Results: The labeling yield was >95%. The radiopeptide showed high uptake value in the U87MG tumor relative to muscle after 2 hours (1.43 ± 0.05 vs. 0.22 ± 0.11 %ID/g). The tumor/muscle ratio was 6.5. Blocking experiment showed specific binding towards tumor. Single-photon emission computed tomography imaging study revealed that radiopeptide had prominent uptake in U87MG tumor., Conclusion: The novel Tc HYNIC- D(RGD) was demonstrated to be a useful radiotracer for the assessment of αvβ3-positive tumor in animal model. Therefore, further clinical and preclinical studies are required.

Background: Although a majority of patients with cutaneous leishmaniasis (CL) are healed with Glucantime chemotherapy, the increased drug resistance rate following its application is a concern. In this study, Naja naja oxiana crude venom of cobra snakes was used for the first time as an assembled combination of bioactive pharmaceutical components on Leishmania major (L. major) standard strain., Objective: To evaluate the efficacy of the Naja naja oxiana crude venom of Iranian cobra snakes on Leishmania major standard strain in vitro., Methods: Five concentrations (1.25, 2.5, 5, 10 and 20 μg/mL) of venom were added to Leishmania major cultures at 24, 48 and 72 h. The viability of the parasites and venom toxicity were assessed by MTT test. The apoptosis was determined by flow cytometry, while IC 50 was determined by counting parasites compared to that of glucantime. Each test was conducted in triplicate., Results: After the exposure of the venom for 72 h, IC 50 value was 0.36 μg/mL and 14.12 μg/mL for promastigotes and amastigotes, respectively. MTT valuation clarified 1.01% promastigotes viability. Furthermore, the results indicated that the venom of Naja naja oxiana induced early and late apoptosis in parasites., Conclusions: The venom of Naja naja oxiana revealed remarkable anti-leishmanial effects as a novel anti-parasitic alternative. Thus, the bioactive and effective fractions of this venom may be considered as anti-leishmanial candidates in future studies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Prostate cancer is a serious threat to men's health so it is necessary to develop technics for early detection of this malignancy. The purpose of this research was the evaluation of a new 99m Tc-labeled GnRH analogue as an imaging probe for tumor targeting of prostate cancer., Methods: 99m Tc-labeled-DLys6-GnRH analogue was prepared based on HYNIC as a chelating agent and tricine/ EDDA as coligands for labeling with 99m Tc. HYNIC was coupled to epsilon amino group of DLys6 through aminobutyric acid (GABA) as a linker. Radiochemical purity and stability in normal saline and serum, were determined by TLC and HPLC methods. Furthermore, calculation of protein-binding and partition coefficient constant were carried out for 99m Tc labeled peptide. The cellular experiments including receptor binding specificity and affinity were studied using three prostate cancer cell lines LN-CaP, DU-145 and PC-3. Finally, the animal assessment and SPECT imaging of radiolabeled GnRH analogue were evaluated on normal mice and nude mice bearing LN-CaP tumor., Results: The GnRH conjugate was labeled with high radiochemical purity (~97%). The radiolabeled peptide showed efficient stability in the presence of normal saline and human serum. The in vitro cellular assays on three prostate cancer cell lines indicated that the radiotracer was bound to LN-CaP cells with higher affinity compared to DU-145 and PC-3 cells. The Kd values of 99m Tc- HYNIC (tricine/ EDDA)-Gaba-D-Lys6GnRH were 89.39±26.71, 93.57±30.49 and107.3±18.82 in LN-CaP, PC-3 and DU-145 cells respectively. The biodistribution studies in normal mice and LN-CaP tumor-bearing nude mice showed similar results including rapid blood clearance and low radioactivity accumulation in non-target organs. High kidney uptake proved that the main excretion route of radiopeptide was through the urinary system. The tumor uptake was 1.72±0.45 %ID/g at 1h p.i. decreasing to 0.70±0.06%ID/g at 4h p.i. for 99m Tc-HYNIC-Gaba-D-Lys6GnRH. The maximum tumor/ muscle ratio was 2.30 at 1h p.i. Pre-saturation of receptor using an excess of unlabeled peptide revealed that the tumor uptake was receptor mediated. The results of the SPECT image of LN-CaP tumor were in agreement with the biodistribution data., Conclusion: Based on this study, we suggest LN-CaP as a favorable cell line for in vivo studies on GnRH analogues. Moreover, this report shows that 99m Tc-HYNIC (tricine/EDDA)-Gaba-D-Lys6GnRH may be a suitable candidate for further evaluation of prostate cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Cancer is the leading cause of death worldwide. Early detection can reduce the disadvantageous effects of diseases and the mortality in cancer. Nuclear medicine is a powerful tool that has the ability to diagnose malignancy without harming normal tissues. In recent years, radiolabeled peptides have been investigated as potent agents for cancer detection. Therefore, it is necessary to modify radiopeptides in order to achieve more effective agents., Objective: This review describes modifications in the structure of radioconjugates with spacers who have improved the specificity and sensitivity of the peptides that are used in oncologic diagnosis and therapy., Methods: To improve the biological activity, researchers have conjugated these peptide analogs to different spacers and bifunctional chelators. Many spacers of different kinds, such as hydrocarbon chain, amino acid sequence, and poly (ethyleneglycol) were introduced in order to modify the pharmacokinetic properties of these biomolecules., Results: Different spacers have been applied to develop radiolabeled peptides as potential tracers in nuclear medicine. Spacers with different charge and hydrophilicity affect the characteristics of peptide conjugate. For example, the complex with uncharged and hydrophobic spacers leads to increased liver uptake, while the composition with positively charged spacers results in high kidney retention. Therefore, the pharmacokinetics of radio complexes correlates to the structure and total charge of the conjugates., Conclusion: Radio imaging technology has been successfully applied to detect a tumor in the earliest stage. For this purpose, the assessment of useful agents to diagnose the lesion is necessary. Developing peptide radiopharmaceuticals using spacers can improve in vitro and in vivo behavior of radiotracers leading to better noninvasive detection and monitoring of tumor growth., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The surface basicity of the alkaline-earth metal oxides has been investigated by studying the properties of 17 O nuclear magnetic resonance (NMR). To this end, we performed density functional theory calculations and determined the 17 O chemical shift and the quadrupolar coupling constants of the regular and stepped surfaces of MO (M = Mg, Ca, Sr, and Ba) oxides. The computed average chemical shift (δ iso av ) for 17 O NMR of bulk MgO, CaO, SrO, and BaO is 46, 301, 394, and 636 ppm, respectively, in excellent agreement with the experiment. The 17 O NMR chemical shifts correlate linearly with the Madelung potential in the four oxides. Next, we considered the changes in the 17 (R = F and OCH 3 (R = F and OCH 3 ) and pyrrole as probe molecules. We found that the 17 O NMR signal of the O ion directly bound to the probe molecule shifts considerably compared to the clean surface. This is due to a change in the polarization of the O charge distribution due to the molecular adsorption. This change is the largest for BaO, with the strongest bond and the shortest surface-adsorbate distance, and the smallest for MgO, thus showing a direct correlation between 17 O NMR and surface basicity. The 17 O chemical shift of the basic site correlates linearly also with several properties of the adsorbed molecules, providing a direct measure of the surface basicity.

Multiple synchronous malignancies are believed to be quite rare and their diagnosis and treatment are very challenging for physicians. Co-presence of synchronous bladder and prostate cancers in an elderly individual is not uncommon; however, the simultaneous occurrence of the third cancer - colon cancer - is extremely outlandish. In the present study, the case of an 82-year-old man with a complaint of hematuria is reported who was eventually diagnosed with three synchronous cancers: stage-3 transitional cell carcinoma of the bladder, stage-4 prostate mucinous adenocarcinoma, and stage-3 glandular adenocarcinoma of the colon. The patient underwent total colectomy and radical cystoprostatectomy followed by chemotherapy and radiotherapy. The 2-year follow-up showed promising results with no major complications and the patient's general condition was satisfactory. Although synchronous cancers are not so common, they should not be disregarded in elderly patients especially in those with multiple symptoms., Competing Interests: The authors report no conflicts of interest in this work., (© 2019 Ghaed et al.)

Overexpression of 15-lipoxygenase-1 (15-LOX-1) enzyme has been reported in prostate tumors, and its expression levels are associated with the degree of cancer malignancy. The aim of this study was to investigate inhibitory effects of stylosin and some similar synthetic monoterpenoids on 15-LOX and also their cytotoxic and anti-cancer activities on prostate cancer cells. Cytotoxicity of compounds was evaluated on prostate cancer cell line "PC-3" and normal human fibroblast "HFF3" cells using AlamarBlue reduction test. The inhibitory effects of the compounds against soybean 15-LOX, a commercially available enzyme, were also assessed. Finally, mechanism of cell death was investigated by flow cytometry. Some of these terpenoids had cytotoxic effects on PC-3 cells, and strong positive correlation was observed between the 15-LOX-1 inhibition potential and the cytotoxicity of the compounds. Moreover, flow cytometry results indicated that apoptosis was the predominant mechanism of induced cell death, which emphasizes the potential of these compounds in prostate cancer therapy. Among studied terpenoids, "fenchyl ferulate" exhibited about three times more cytotoxicity than cisplatin. Strong positive correlation observed between 15-LOX inhibition potential and cytotoxicity of the compounds indicates selective anti-cancer properties of the compounds might be exerted via inhibition of 15-LOX-1 in PC-3 cells. Furthermore, observed cytotoxicity is mediated through apoptosis, which is probably triggered via 15-LOX-1 inhibition.

This review is a broad survey of ion exchange membranes (IEMs) in chosen areas of analytical chemistry. The coverage is comprehensive in ion chromatography (IC) applications, this includes in-line water purification for IC use, chemical and electrodialytic eluent suppression, eluent generation, eluent purification, pH modification, buffer generation, use in ion exclusion chromatography, charge-based detection, as well as suppressor-detector combinations. The use of IEMs in sample treatment using ion transfer devices and Donnan dialysis preconcentration are discussed. Introduction of reagents through an IEM, whether through a concentration gradient large enough to overcome the Donnan barrier or active electrodialysis, does not involve volumetric dilution. Reagent introduction in this fashion, enabling conductometric detection of otherwise non-ionized weak electrolytes, is discussed. Several important applications of IEMs, in which ion exchange plays little or no role, are discussed; these include (a) diffusion-based gas collection and analysis, (b) evaporative concentration in a flow system, (c) drying of gas streams and (d) sensing of moisture in gases and liquids. An important area that is not covered is ion-sensing with IEMs and/or ionophores., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Gene set analysis is a well-established approach for interpretation of data from high-throughput gene expression studies. Achieving reproducible results is an essential requirement in such studies. One factor of a gene expression experiment that can affect reproducibility is the choice of sample size. However, choosing an appropriate sample size can be difficult, especially because the choice may be method-dependent. Further, sample size choice can have unexpected effects on specificity., Results: In this paper, we report on a systematic, quantitative approach to study the effect of sample size on the reproducibility of the results from 13 gene set analysis methods. We also investigate the impact of sample size on the specificity of these methods. Rather than relying on synthetic data, the proposed approach uses real expression datasets to offer an accurate and reliable evaluation., Conclusion: Our findings show that, as a general pattern, the results of gene set analysis become more reproducible as sample size increases. However, the extent of reproducibility and the rate at which it increases vary from method to method. In addition, even in the absence of differential expression, some gene set analysis methods report a large number of false positives, and increasing sample size does not lead to reducing these false positives. The results of this research can be used when selecting a gene set analysis method from those available.

Gene set analysis is a quantitative approach for generating biological insight from gene expression datasets. The abundance of gene set analysis methods speaks to their popularity, but raises the question of the extent to which results are affected by the choice of method. Our systematic analysis of 13 popular methods using 6 different datasets, from both DNA microarray and RNA-Seq origin, shows that this choice matters a great deal. We observed that the overall number of gene sets reported by each method differed by up to 2 orders of magnitude, and there was a bias toward reporting large gene sets with some methods. Furthermore, there was substantial disagreement between the 20 most statistically significant gene sets reported by the methods. This was also observed when expanding to the 100 most statistically significant reported gene sets. For different datasets of the same phenotype/condition, the top 20 and top 100 most significant results also showed little to no agreement even when using the same method. GAGE, PAGE, and ORA were the only methods able to achieve relatively high reproducibility when comparing the 20 and 100 most statistically significant gene sets. Biological validation on a juvenile idiopathic arthritis (JIA) dataset showed wide variation in terms of the relevance of the top 20 and top 100 most significant gene sets to known biology of the disease, where GAGE predicted the most relevant gene sets, followed by GSEA, ORA, and PAGE.

Competing Interests: Conflict of interest The authors declare that there is no conflict of interests.

Aims: The aim of this study was to evaluate outcomes and fusion rates of 4 different methods of first metatarsophalangeal joint (MTPJ) arthrodesis., Methods: We performed a retrospective analysis of first MTPJ fusion using Bold® and Acutrak® compression screws, universal 1/3 tubular plate and Hallu®-S non-locking plate in 6 hospitals in Dublin over 4 years. A cohort of 300 patients (351 feet) was operated on by 3 feet and ankle fellowship trained orthopaedic surgeons (PK, MMS, JVMcK) over 4 years. Mean age was 62.4 years. There were 261 females and 39 males. One hundred three patients had a fusion of first MTPJ using two Acutrak® screws and 90 with two Bold® screws. Sixty-five were fused with the Hallu-S® plate and 42 with the universal 1/3 tubular plate. Patients were evaluated clinically and radiographically at 6 weeks, 3 months and 12 months., Results: Functional outcome scores performed using Manchester-Oxford Foot Questionnaire (MOXFQ). Failure rate in those fused with the Hallu®-S plate was 0%, Acutrak® screws 2.4%, Bold® screws 9.5% and universal 1/3 tubular plate 12.5% (p > 0.12). All treatment groups demonstrated significantly reduced MOXFQ scores (p value < 0.05)., Conclusion: In this retrospective study for first MTPJ fusion, a low profile, pre-contoured plate in combination with a screw mode had the best results with no failure rates and improved MOXFQ scores., Level of Clinical Evidence: IV, retrospective study.

Cervical cancer is among the most common type of cancers in women and is associated with human papillomavirus (HPV) infection. Genital warts are also reported to be linked with HPV infection types 11 and 6. In turn, clinical characteristics and morphological features of warts may be useful in the prediction of prognosis and in making treatment decisions. Thus, we have investigated the association of high and low-risk HPVs genotype with genital wart risk, as well as pathological and cytological information in cases recruited from a population-based cohort study of 1380 patients. Patients infected with HPV genotype 6 or 11 had an increased risk of having warts, with OR of 2.34 (95% CI: 0.955-5.737, P = 0.06). Also, this association was enhanced in the presence of high plus low-risk HPV for having genital wart (OR: 2.814; 95%: 1.208-6.55, P = 0.017) and cases having high-risk HPV (OR: 2.329; 95% CI: 1.029-5.269, P = 0.042). Moreover, we observed patients with genital warts having CIN2/3, indicating the importance of informing the physician to the patient to prevent more severe lesions. Our data demonstrated that patients with both low/high-risk HPV types had an increased risk of developing genital warts and persistent infection with HPV was a necessary precursor for the increase in cervical lesions., (© 2019 Wiley Periodicals, Inc.)

Background: TGFαL3-SEB chimeric protein is a synthetic protein, which is produced by combining the third loop (L3) of transforming growth factor-α (TGF-α) with staphylococcal enterotoxin type B. To the best of our knowledge, anti-cancer activity of this chimeric protein against colon cancer that overexpresses epidermal growth factor receptor (EGFR) has not yet been studied. Thus, in the present study, the anti-tumor effects of TGFαL3-SEB chimeric protein on HT-29 colon cancer cells were evaluated., Materials and Methods: The TGFαL3-SEB chimeric protein was previously designed and cloned in Escherichia coli (E. coli) [1,2]. The level of expression and the purity of this novel protein were examined for further analysis. For this purpose, the cells were treated with different concentrations (25, 50 and 75 μg/ml) of TGFαL3-SEB and then the proliferation was detected using the MTT assay. The apoptosis-inducing potential of TGFαL3-SEB in HT-29 and HEK-293 cells was evaluated by flow cytometry using Annexin V/PI double staining method; in addition, bax/bcl2 mRNA ratio, caspase-3 and caspase-9 activity were also assessed., Results: In the present study, TGFαL3-SEB chimeric protein was produced in E. coli. After effective purification, its growth inhibitory effect was evaluated. Our results indicated that the incubation of HT-29 colon cancer cell with 25, 50 and 75 μg/ml of TGFαL3-SEB for 24 h leads to significant reduction of proliferation in a dose-dependent manner (P < 0.05). Further analysis indicated that exposure of EGFR expressing HT-29 cells to TGFαL3-SEB leads to significant increase of the caspase-3 and caspase-9 activity in a concentration-dependent manner (P < 0.05). Bax/bcl-2 ratio also confirmed that TGFαL3-SEB has the pro-apoptotic effect. Flow cytometry analysis of TGFαL3-SEB treated cells showed that in addition to apoptotic cells, necrotic cells were also increased significantly at the concentration of 25, 50 and 75 μg/ml (P < 0.05)., Conclusion: In conclusion, our results demonstrated that TGFαL3-SEB chimeric protein induced cell death through both mechanisms of apoptosis and necrosis in HT-29 colon cancer cells. This paper has highlighted that TGFαL3-SEB has the potential to target EGFR expressing cancer cell., (Copyright © 2018 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Cervical cancer (CC) is a common malignancy in women and a major cause of cancer-related mortality globally. Some novel biomarkers may enable the early diagnosis and monitoring of CC. MicroRNAs (miRNAs) are small noncoding RNAs that control gene translation at a posttranscriptional level. Hence the deregulation of these molecules can cause many diseases. There appears to be an association between aberrant miRNA expression and CC, but the molecular mechanisms involved in the development of CC remain unknown. The upregulation of some circulating miRNAs, for example, miRNA-20a, miRNA-203, miRNA-21, miRNA-205, miRNA-218, and miR-485-5, as well as tissue-specific miRNAs, for example, miR-7, miR-10a, miR-17-5p, miR-135b, miR-149, and miR-203 have been found in patients with CC. There is also growing evidence for the importance of miRNAs in the development of drug resistance. This review therefore highlights recently published preclinical and clinical investigation performed on tissue specific and circulating miRNAs, as potential biomarkers for the detection of patients at early stages of CC, in the prediction of prognosis, and monitoring of their response to therapy., (© 2018 Wiley Periodicals, Inc.)