MV1035 Overcomes Temozolomide Resistance in Patient-Derived Glioblastoma Stem Cell Lines

Glioblastoma (GBM, grade IV glioma) represents the most aggressive brain tumor and patients with GBM have a poor prognosis. Until now surgical resection followed by radiotherapy and temozolomide (TMZ) treatment represents the standard strategy for GBM. We showed that the imidazobenzoxazin-5-thione MV1035 is able to significantly reduce GBM U87-MG cells migration and invasiveness through inhibition of the RNA demethylase ALKBH5. In this work, we focus on the DNA repair protein ALKBH2, a further MV1035 target resulting from SPILLO-PBSS proteome-wide scale in silico analysis. Our data demonstrate that MV1035 inhibits the activity of ALKBH2, known to be involved in GBM TMZ resistance. MV1035 was used on both U87-MG and two patient-derived (PD) glioma stem cells (GSCs): in combination with TMZ, it has a significant synergistic effect in reducing cell viability and sphere formation. Moreover, MV1035 induces a reduction in MGMT expression in PD-GSCs cell lines most likely through a mechanism that acts on MGMT promoter methylation. Taken together our data show that MV1035 could act as an inhibitor potentially helpful to overcome TMZ resistance and able to reduce GBM migration and invasiveness.

Plasmodium falciparum histidine rich protein 2 (pfhrp2): an additional genetic marker suitable for anti-malarial drug efficacy trials

Background Genotyping of the three Plasmodium falciparum polymorphic genes, msp1, msp2 and glurp, has been adopted as a standard strategy to distinguish recrudescence from new infection in drug efficacy clinical trials. However, the suitability of a particular gene is compromised in areas where its allelic variants distribution is significantly skewed, a phenomenon that might occur in isolated parasite populations or in areas of very low transmission. Moreover, observation of amplification bias has diminished the value of glurp as a marker. Methods The suitability of the polymorphic P. falciparum histidine-rich protein 2 (pfhrp2) gene was assessed to serve as an alternative marker using a PCR-sequencing or a PCR–RFLP protocol for genotyping of samples in drug efficacy clinical trials. The value of pfhrp2 was validated by side-by-side analyses of 5 admission-recrudescence sample pairs from Yemeni malaria patients. Results The outcome of the single pfhrp2 gene discrimination analysis has been found consistent with msp1, msp2 and glurp pool genotyping analysis for the differentiation of recrudescence from new infection. Conclusion The findings suggest that under the appropriate circumstances, pfhrp2 can serve as an additional molecular marker for monitoring anti-malarials efficacy. However, its use is restricted to endemic areas where only a minority of P. falciparum parasites lack the pfhrp2 gene.

COVID-19 with essential thrombocythemia treated with apixaban for antithrombotic prophylaxis

A 40-year-old man was admitted to our hospital for COVID-19. He had been treated for essential thrombocythemia (ET). He was diagnosed severe illness of COVID-19, oxygen therapy and dexamethasone were administered. There was a possibility of thromboembolic events in this case, apixaban for prophylaxis was added. With these treatments, the patient has made a good recovery, and he was discharged on hospital day 11. There is no standard strategy for prophylaxis of thrombosis in patients with ET, and apixaban could be a clinical benefit for these patients.

Digital Advertising Features on Customer Purchase Intention

Advertisement denotes a standard strategy of attracting public interest and facilitating purchase decisions. This research aims to determine the digital advertisement feature effects on consumer purchase intent in Malaysia. A cross-sectional design was employed to gather quantitative data from 361 Malaysian respondents with a digital survey. Additionally, SPSS was utilised to assess the digital advertising-purchase intention relationship. Resultantly, pictorial cues, repetition, and sensory stores significantly influenced Malaysian consumers’ purchase intention. Following the motivation theory, this research identified a relationship between digital advertising feature effects and purchase intention power that proved inadequate in past studies. The study outcome proved vital in rearranging advertising methods to be more appealing and informative for customers to receive clear and precise knowledge.

Efficiency of DNA Mini-Barcoding to Assess Mislabeling in Commercial Fish Products in Italy: An Overview of the Last Decade

The problem of fish traceability in processed products is still an important issue in food safety. Major attention is nowadays dedicated to consumer health and prevention of possible frauds regulated by national and international laws. For this reason, a technical approach is fundamental in revealing mislabeling at different levels. In particular, the use of genetic markers has been standardized and DNA barcoding is considered the gold-standard strategy to examine and prevent species substitution. Considering the richness of available DNA databases, it is nowadays possible to rapidly reach a reliable taxonomy at the species level. Among different approaches, an innovative method based on DNA mini barcoding has recently been proposed at an international level. Starting from this evidence, we herein illustrate an investigation dealing with the evolution of this topic in Italy over the last decade. The molecular analysis of 71 commercial fish samples based on mini-COI sequencing with two different primer sets reached an amplification success rate of 87.3 and 97.2%. The investigation revealed four major frauds (5.8%) and four minor ones (5.8%). Results highlighted a decrease in incorrect labeling in Italy from 32% to 11.6% over the last decade, although a recurrent involvement of “endangered” species sensu IUCN was still observed.

Electrochemical Degradation of DSW Using Fe- Fe and Al- Al Electrodes Taguchi and Anova Approach

Expulsion of toxins from distillery spent wash (DSW) was applied by utilizing a blend of matched aluminum and iron electrodes in a clump method of activity utilizing electrochemical procedure. The refinery spent wash was described diagnostically utilizing standard strategy for examination and the treatment results were dissected as far as COD and Colour. The examinations were directed to consider the impact of working boundaries, for example, voltage, separation between the electrodes and electrolysis time and were optimized by utilizing Taguchi and ANOVA technique. pH and stirring speed were kept constant as 7 and 500 rpm. The most extreme expulsion efficiencies of COD and Colour were monitored by considering total of 16 experiments each with three trials. The Taguchi method led to COD of 95% and color removal of 94%, optimized with Al-Al electrodes at the voltage of 25V, distance of electrodes 2 cm and the electrolysis time of 150 minutes. The most extreme COD and Colour removal efficiencies found to be 92% and 89% from Fe-Fe electrodes at the indistinguishable working conditions. In any case, the aluminum electrodes seen progressively appropriate for the deprivation of DSW when contrasted with iron electrodes.

An Automated Correction Algorithm (ALPACA) for ddPCR Data Using Adaptive Limit of Blank and Correction of False Positive Events Improves Specificity of Mutation Detection

Background Bio-Rad droplet-digital PCR is a highly sensitive method that can be used to detect tumor mutations in circulating cell-free DNA (cfDNA) of patients with cancer. Correct interpretation of ddPCR results is important for optimal sensitivity and specificity. Despite its widespread use, no standardized method to interpret ddPCR data is available, nor have technical artifacts affecting ddPCR results been widely studied. Methods False positive rates were determined for 6 ddPCR assays at variable amounts of input DNA, revealing polymerase induced false positive events (PIFs) and other false positives. An in silico correction algorithm, known as the adaptive LoB and PIFs: an automated correction algorithm (ALPACA), was developed to remove PIFs and apply an adaptive limit of blank (LoB) to individual samples. Performance of ALPACA was compared to a standard strategy (no PIF correction and static LoB = 3) using data from commercial reference DNA, healthy volunteer cfDNA, and cfDNA from a real-life cohort of 209 patients with stage IV nonsmall cell lung cancer (NSCLC) whose tumor and cfDNA had been molecularly profiled. Results Applying ALPACA reduced false positive results in healthy cfDNA compared to the standard strategy (specificity 98 vs 88%, P = 10−5) and stage IV NSCLC patient cfDNA (99 vs 93%, P = 10−11), while not affecting sensitivity in commercial reference DNA (70 vs 68% P = 0.77) or patient cfDNA (82 vs 88%, P = 0.13). Overall accuracy in patient samples was improved (98 vs 92%, P = 10−7). Conclusions Correction of PIFs and application of an adaptive LoB increases specificity without a loss of sensitivity in ddPCR, leading to a higher accuracy in a real-life cohort of patients with stage IV NSCLC.

Positioning Practices of Orientation and Mobility Specialists When Teaching Street Crossings: Is There a Standard Approach?

Introduction: An important skill for orientation and mobility (O&M) specialists to have is to monitor clients appropriately when they are learning to cross intersections. Techniques books provide some suggestions for positioning during street crossings, but no research has been conducted about consensus or priorities for making appropriate decisions on positioning. The purpose of this study was to investigate general positioning decisions using visual monitoring techniques. Method: A total of 234 participants (practicing O&M specialists, preservice O&M students, and O&M university personnel) completed a 40-question survey. The survey included demographic questions, diagrams of intersections that participants used to select positioning locations, questions about lanes of threat, and questions about important factors to consider when positioning to monitor safety. Commonality of selections were analyzed and compared with demographic information. Results: The greatest consensus was found for all intersection types when the client is positioned on the corner waiting to cross and for identification of the first lane of threat. More variable position selections were made for monitoring during the crossings, and the second and third lane of threat selections were also more variable. Factors respondents indicated as most important to consider when positioning aligned with their positioning choices overall. Discussion: Personnel preparation programs may want to consider to what extent they teach considerations for positioning before and during crossings, and whether the predominant tendency to put oneself between the client and traffic warrants additional conversation. Future research should look at more complex intersections and the additional nuances used to make positioning choices. Implications for practitioners: Practitioners should reflect on whether they actively change their positioning decisions based on the situation and type of intersection versus tending to use a standard strategy.