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Recently, the development of eco-friendly, cost-effective and reliable methods for synthesis of metal nanoparticles has drawn a considerable attention. The so-called green synthesis, using mild reaction conditions and natural resources as plant extracts and microorganisms, has established as a convenient, sustainable, cheap and environmentally safe approach for synthesis of a wide range of nanomaterials. Over the past decade, biosynthesis is regarded as an important tool for reducing the harmful effects of traditional nanoparticle synthesis methods commonly used in laboratories and industry. This review emphasizes the significance of biosynthesized metal nanoparticles in the field of electrochemical sensing. There is increasing evidence that green synthesis of nanoparticles provides a new direction in designing of cost-effective, highly sensitive and selective electrode-catalysts applicable in food, clinical and environmental analysis. The article is based on 157 references and provided a detailed overview on the main approaches for green synthesis of metal nanoparticles and their applications in designing of electrochemical sensor devices. Important operational characteristics including sensitivity, dynamic range, limit of detection, as well as data on stability and reproducibility of sensors have also been covered.

Abstract Background Many analyses of microarray association studies involve permutation, bootstrap resampling and cross-validation, that are ideally formulated as embarrassingly parallel computing problems. Given that these analyses are computationally intensive, scalable approaches that can take advantage of multi-core processor systems need to be developed. Results We have developed a CUDA based implementation, permGPU, that employs graphics processing units in microarray association studies. We illustrate the performance and applicability of permGPU within the context of permutation resampling for a number of test statistics. An extensive simulation study demonstrates a dramatic increase in performance when using permGPU on an NVIDIA GTX 280 card compared to an optimized C/C++ solution running on a conventional Linux server. Conclusions permGPU is available as an open-source stand-alone application and as an extension package for the R statistical environment. It provides a dramatic increase in performance for permutation resampling analysis in the context of microarray association studies. The current version offers six test statistics for carrying out permutation resampling analyses for binary, quantitative and censored time-to-event traits.

Background and Purpose: Diclofenac (DCF) is a non-steroidal anti-inflammatory drug possessing analgesic and antipyretic properties. It is used for the treatment of rheumatoid arthritis pain, osteoarthritis, and acute muscle pain conditions and can be administrated orally, topically or intravenously. Because of its widespread use, hydrophilicity, stability and poor degradation (bioaccumulation in the food chain), DCF is an emerging chemical contaminant that can cause adverse effects in the ecosystems. Taking into account the consumption of DCF in pharmaceutical formulations and its negative impact on the environment, the development of new sensitive, selective, cheap, fast, and online capable analytical devices is needed for on-site applications., Experimental Approach: This brief review attempts to cover the recent developments related to the use of nanomaterials as catalysts for electrochemical determination of DCF in pharmaceutical formulations, biological fluids and environmental samples., Key Results: The article aims to prove how electrochemical sensors represent reliable alternatives to conventional methods for DCF analysis., Conclusion: The manuscript highlights the progress in the development of electrochemical sensors for DCF detection. We have analyzed numerous recent papers (mainly since 2019) on sensors developed for the quantitative determination of DCF, indicating the limit of detection, linear range, stability, reproducibility, and analytical applications. Current challenges related to the sensor design and future perspectives are outlined., Competing Interests: Conflict of interest: The authors declare no conflict of interest., (Copyright © 2024 by the authors.)

Reliable, rapid, highly selective and sensitive analytical methods for the determination of antineoplastic agent 5-fluorouracil (5-FU) in human body fluids (blood serum/plasma and urine) are required to improve the chemotherapy regimen to reduce its toxicity and improve efficacy. Nowadays, electrochemical techniques provide a powerful analytical tool for 5-FU detection systems. This comprehensive review covers the advances in the development of electrochemical sensors for the quantitative determination of 5-FU, mainly focused on original studies reported from 2015 to date. We have summarized recent trends in the electrochemical sensor systems applied for the analysis of 5-FU in pharmaceutical formulations and biological samples, and critically evaluated the key performance metrics of these sensors (limit of detection, linear range, stability and recovery). Challenges and future outlooks in this field have also been discussed., Competing Interests: Conflict of interest: The author declares no conflict of interest., (Copyright © 2023 by the authors.)

Nowadays, micro-sized sensors have become a hot topic in electroanalysis. Because of their excellent analytical features, microelectrodes are well-accepted tools for clinical, pharmaceutical, food safety, and environmental applications. In this brief review, we highlight the state-of-art electrochemical non-enzymatic microsensors for quantitative detection of ascorbic acid (also known as vitamin C). Ascorbic acid is a naturally occurring water-soluble organic compound with antioxidant properties and its quantitative determination in biological fluids, foods, cosmetics, etc., using electrochemical microsensors is of wide interest. Various electrochemical techniques have been applied to detect ascorbic acid with extremely high sensitivity, selectivity, reproducibility, and reliability, and apply to in vivo measurements. This review paper aims to give readers a clear view of advances in areas of electrode modification, successful strategies for signal amplification, and miniaturization techniques used in the electroanalytical devices for ascorbic acid. In conclusion, current challenges related to the microelectrodes design, and future perspectives are outlined.

Purpose: CALGB 90206 was a phase III trial of 732 patients with metastatic renal cell carcinoma (mRCC) comparing bevacizumab plus IFNα (BEV + IFN) with IFNα alone (IFN). No difference in overall survival (OS) was observed. Baseline samples were analyzed to identify predictive biomarkers for survival benefit., Patients and Methods: A total of 32 biomarkers were assessed in 498 consenting patients randomly assigned into training (n = 279) and testing (n = 219) sets. The proportional hazards model was used to test for treatment arm and biomarker interactions of OS. The estimated coefficients from the training set were used to compute a risk score for each patient and to classify patients by risk in the testing set. The resulting model was assessed for predictive accuracy using the time-dependent area under the ROC curve (tAUROC)., Results: A statistically significant three-way interaction between IL6, hepatocyte growth factor (HGF), and bevacizumab treatment was observed in the training set and confirmed in the testing set (P < 0.0001). The model based on IL6, HGF, and bevacizumab treatment was predictive of OS (P < 0.001), with the high- and low-risk groups having a median OS of 10.2 [95% confidence interval (CI), 8.0-13.8] and 34.3 (95% CI, 28.5-40.5) months, respectively. The average tAUROC for the final model of OS based on 100 randomly split testing sets was 0.78 (first, third quartiles = 0.77, 0.79)., Conclusions: IL6 and HGF are potential predictive biomarkers of OS benefit from BEV + IFN in patients with mRCC. The model based on key biological and clinical factors demonstrated predictive efficacy for OS. These markers warrant further validation in future anti-VEGF and immunotherapy in mRCC trials. See related commentaries by Mishkin and Kohn, p. 2722 and George and Bertagnolli, p. 2725., (©2021 American Association for Cancer Research.)

Ruthenium oxide hexacyanoferrate (RuOHCF) film was electrochemically deposited on to a glassy carbon (GC) surfaceusing consecutive cyclic voltammetry as a facile and green synthetic strategy. The electrochemical behaviour and electrocatalytic properties of the modified electrode Ru?HCF/GC were evaluated with regards to electroreduction of hydrogen peroxide and iodate in a strong acidic medium (pHs 1.0-2.0) by using different electrochemical techniques, including cyclic voltammetry and amperometry at a constant potential. Electrochemical studies indicated that Ru?HCF/GC possess a high catalytic activity in both studied reactions, fast response and good reproducibility of the current signal. The Ru?HCF/GC exhibits enhanced electrocatalytic behaviour compared with other modified electrodes reported before. The simple and reproducible procedure for electrode fabrication, the wide linear range, anti-interference performance and long-time stability of the Ru?HCF/GC make it a promising sensing material for practical quantitative determination of hydrogen peroxide and iodate. Remarkably, the reported modified.

Over the past two decades, electrochemical biosensor devices have received great attention in the field of food analysis owing to their attractive performances. In the food industry the quality control during manufacturing process and final products requires quick and reliable analytical methods. A promising alternative to the traditional analytical techniques are the electrochemical enzymatic biosensors - devices that combine the robustness of electrochemical techniques with the specificity of biological recognition processes and offer great advantages due to size, cost, sensitivity, selectivity, and fast response. This brief review has attempted to summarise the literature on the recent progress in the development of enzyme biosensors with amperometric detection for quantitative analysis of glucose and lactate in various food samples. The review concludes with an outlook on the future challenges and perspectives in this area.

Background: Parametric feature selection methods for machine learning and association studies based on genetic data are not robust with respect to outliers or influential observations. While rank-based, distribution-free statistics offer a robust alternative to parametric methods, their practical utility can be limited, as they demand significant computational resources when analyzing high-dimensional data. For genetic studies that seek to identify variants, the hypothesis is constrained, since it is typically assumed that the effect of the genotype on the phenotype is monotone (e.g., an additive genetic effect). Similarly, predictors for machine learning applications may have natural ordering constraints. Cross-validation for feature selection in these high-dimensional contexts necessitates highly efficient computational algorithms for the robust evaluation of many features., Results: We have developed an R extension package, fastJT, for conducting genome-wide association studies and feature selection for machine learning using the Jonckheere-Terpstra statistic for constrained hypotheses. The kernel of the package features an efficient algorithm for calculating the statistics, replacing the pairwise comparison and counting processes with a data sorting and searching procedure, reducing computational complexity from O(n 2 ) to O(n log(n)). The computational efficiency is demonstrated through extensive benchmarking, and example applications to real data are presented., Conclusions: fastJT is an open-source R extension package, applying the Jonckheere-Terpstra statistic for robust feature selection for machine learning and association studies. The package implements an efficient algorithm which leverages internal information among the samples to avoid unnecessary computations, and incorporates shared-memory parallel programming to further boost performance on multi-core machines.

Iridium oxide (IrOx) was electrodeposited onto glassy carbon electrode applying two-step potential cycling procedure. The electrocatalytic properties of the modified electrode IrOx/GC were evaluated with regards to electrochemical oxidation of nitrite and ascorbic acid (AA). The developed electrode-catalyst have been extensively studied by various electrochemical techniques. Differential pulse voltammetry (DPV) experiments indicated that the modified electrode possesses excellent electrocatalytic activity towards the oxidation of both nitrite and AA in neutral medium and offers simultaneous quantification of these substances. Constant potential amperometry studies also were performed - the IrOx/GC showed sensitive response to nitrite (159.7 μA mM-1 cm-2) with a wide linear range from 0.002 to 10 mM at 0.77 V (vs. Ag/AgCl, 3 M KCl), and to AA (96.2 µA mM-1cm-2) with a linear range from 0.01 to 3 mM at 0.025 V. The detection limit was 0.63 μM nitrite and 4 μM AA, respectively, and both of them had fast response within 5 s. Considering the simple and rapid electrodeposition procedure for preparation, IrOx/GC is a new electrode-catalyst for sensitive and selective quantitative detection of nitrite and AA. The wide linear range, good selectivity, reproducibility of the amperometric response and long-time stability of the IrOx/GC make it a promising sensing material for practical nonenzymatic quantitative detection of nitrite and AA.

Purpose: Discovery of SNPs that predict a patient's risk of docetaxel-induced neuropathy would enable treatment individualization to maximize efficacy and avoid unnecessary toxicity. The objectives of this analysis were to discover SNPs associated with docetaxel-induced neuropathy and mechanistically validate these associations in preclinical models of drug-induced neuropathy., Experimental Design: A genome-wide association study was conducted in metastatic castrate-resistant prostate cancer patients treated with docetaxel, prednisone and randomized to bevacizumab or placebo on CALGB 90401. SNPs were genotyped on the Illumina HumanHap610-Quad platform followed by rigorous quality control. The inference was conducted on the cumulative dose at occurrence of grade 3+ sensory neuropathy using a cause-specific hazard model that accounted for early treatment discontinuation. Genes with SNPs significantly associated with neuropathy were knocked down in cellular and mouse models of drug-induced neuropathy., Results: A total of 498,081 SNPs were analyzed in 623 Caucasian patients, 50 (8%) of whom experienced grade 3+ neuropathy. The 1,000 SNPs most associated with neuropathy clustered in relevant pathways including neuropathic pain and axonal guidance. An SNP in VAC14 (rs875858) surpassed genome-wide significance (P = 2.12 × 10 -8 , adjusted P = 5.88 × 10 -7 ). siRNA knockdown of VAC14 in stem cell-derived peripheral neuronal cells increased docetaxel sensitivity as measured by decreased neurite processes (P = 0.0015) and branches (P < 0.0001). Prior to docetaxel treatment, VAC14 heterozygous mice had greater nociceptive sensitivity than wild-type litter mate controls (P = 0.001)., Conclusions: VAC14 should be prioritized for further validation of its potential role as a predictor of docetaxel-induced neuropathy and biomarker for treatment individualization. Clin Cancer Res; 22(19); 4890-900. ©2016 AACR., Competing Interests: The authors declare the following relevant conflicts of interest., (©2016 American Association for Cancer Research.)

Ionizing radiation (IR) is a major source of cellular damage and the immediate cellular response to IR has been well characterized. But the long-term impact of IR on cell function and its relationship with aging are not known. Here, we examined the IR effects on telomere length and other biomarkers 50 to 68 years post-exposure (two time points per person) in survivors of the atomic bombing at Hiroshima during WWII. We found that telomere length of leukocytes was inversely correlated with the dose of IR (p=0.008), and this effect was primarily found in survivors who were exposed at younger ages; specifically those <12 years old (p=0.0004). Although a dose-related retardation of telomere shortening with age was observed in the cross-sectional data, longitudinal follow-up after 11 years did not show IR exposure-related alteration of the rate of telomere shortening with age. In addition, IR diminished the associations between telomere length and selected aging biomarkers that were observed in survivors with no dose. These included uric acid metabolism, cytokines, and blood T cell counts. These findings showed long-lasting detrimental effects of IR on telomere length of leukocytes in both dose- and age-at-exposure dependent manner, and on alterations of biomarkers with aging., Competing Interests: CONFLICTS OF INTREST The authors declare no conflict of interests.

Purpose: Formalin-fixed, paraffin-embedded tumor samples from CALGB 80203 were analyzed for expression of EGFR axis-related genes to identify prognostic or predictive biomarkers for cetuximab treatment., Patients and Methods: Patients (238 total) with first-line metastatic colorectal cancer (mCRC) were randomized to FOLFOX or FOLFIRI chemotherapy ± cetuximab. qRT-PCR analyses were conducted on tissues from 103 patients at baseline to measure gene expression levels of HER-related genes, including amphiregulin (AREG), betacellulin (BTC), NT5E (CD73), DUSP4, EGF, EGFR, epigen (EPGN), epiregulin (EREG), HBEGF, ERBB2 (HER2), ERBB3 (HER3), ERBB4 (HER4), PHLDA1, and TGFA. The interactions between expression levels and treatment with respect to progression-free survival (PFS) and overall survival (OS) were modeled using multiplicative Cox proportional hazards models., Results: High tumor mRNA levels of HER2 [hazard ratio (HR), 0.64; P = 0.002] and EREG (HR, 0.89; P = 0.016) were prognostic markers associated with longer PFS across all patients. HER3 and CD73 expression levels were identified as potential predictive markers of benefit from cetuximab. In KRAS wild-type (WT) tumors, low HER3 expression was associated with longer OS from cetuximab treatment, whereas high HER3 expression was associated with shorter OS from cetuximab treatment (chemo + cetuximab: HR, 1.15; chemo-only: HR, 0.48; Pinteraction = 0.029). High CD73 expression was associated with longer PFS from cetuximab treatment in patients with KRAS-WT (chemo + cetuximab: HR, 0.91; chemo-only: HR, 1.57; Pinteraction = 0.026) and KRAS-mutant (Mut) tumors (chemo + cetuximab: HR, 0.80; chemo-only: HR, 1.29; P = 0.025)., Conclusions: Gene expression of HER3 and CD73 was identified as a potential predictive marker for cetuximab. These data implicate HER axis signaling and immune modulation as potential mechanisms of cetuximab action and sensitivity., (©2014 American Association for Cancer Research.)

Purpose: We sought to show the relevance of a lymphoblastoid cell line (LCL) model in the discovery of clinically relevant genetic variants affecting chemotherapeutic response by comparing LCL genome-wide association study (GWAS) results to clinical GWAS results., Experimental Design: A GWAS of paclitaxel-induced cytotoxicity was conducted in 247 LCLs from the HapMap Project and compared with a GWAS of sensory peripheral neuropathy in patients with breast cancer (n = 855) treated with paclitaxel in the Cancer and Leukemia Group B (CALGB) 40101 trial. Significant enrichment was assessed by permutation resampling analysis., Results: We observed an enrichment of LCL cytotoxicity-associated single-nucleotide polymorphisms (SNP) in the sensory peripheral neuropathy-associated SNPs from the clinical trial with concordant allelic directions of effect (empirical P = 0.007). Of the 24 SNPs that overlap between the clinical trial (P < 0.05) and the preclinical cytotoxicity study (P < 0.001), 19 of them are expression quantitative trait loci (eQTL), which is a significant enrichment of this functional class (empirical P = 0.0447). One of these eQTLs is located in RFX2, which encodes a member of the DNA-binding regulatory factor X family. Decreased expression of this gene by siRNA resulted in increased sensitivity of Neuroscreen-1(NS-1; rat pheochromocytoma) cells to paclitaxel as measured by reduced neurite outgrowth and increased cytotoxicity, functionally validating the involvement of RFX2 in nerve cell response to paclitaxel., Conclusions: The enrichment results and functional example imply that cellular models of chemotherapeutic toxicity may capture components of the underlying polygenic architecture of related traits in patients., (©2012 AACR.)