CAFs-secreted exosomal cricN4BP2L2 promoted colorectal cancer stemness and chemoresistance by interacting with EIF4A3

alexandrossfakianakis shared this article with you from Inoreader CAFs-secreted exosomal cricN4BP2L2 promoted colorectal cancer stemness and chemoresistance by interacting with EIF4A3 via ScienceDirect Publication: Experimental Cell Research Publication date: Available online 22 June 2022 Source: Experimental Cell Research Author(s): Zhan Qu, Ke-Da Yang, Bai-Hua Luo, Fan Zhang View on Web

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Drugs‐associated with red man syndrome: An integrative approach using disproportionality analysis and Pharmip

alexandrossfakianakis shared this article with you from Inoreader Drugs‐associated with red man syndrome: An integrative approach using disproportionality analysis and Pharmip via Journal of Clinical Pharmacy and Therapeutics We performed a retrospective disproportionality analysis exploiting FAERS database and unveiled drugs associated with Red man syndrome. Further, a novel in silico technique of PHARMIP was used followed by molecular docking to signify the role of Carbonic anhydrase II and MRGPRX2 in causing the event. Corroborating the drugs causing the adverse event with the genes revealed Oritavancin to have the highest affinity. This indicated the potentiality of this drug to cause Red man syndrome. Abstract What is known and objective Red man syndrome (RMS) is a non-IgE-mediated anaphylactoid adverse event frequently witnessed after a rapid infusion of vancomycin. This study aims to unravel drugs and associated off-label targets that induce RMS by exploiting FDA Adverse Event Reporting System (FAERS) and Pharmacovigilance/Pharmacogenomics Insilico Pipeline (PHARMIP). Methods The case/non-case retrospective observational study was conducted in the FAERS database. Reporting odds ratio (ROR) and proportional reporting ratio (PRR) data mining algorithms were used to evaluate the strength of the signal. The off-label targets of the drugs with potential signals were obtained using online servers by applying a similarity ensemble approach and a reverse pharmacophore database, which was further validated by molecular docking studies. Results and discussion Oritavancin exhibited a strong positive signal (PRR:1185.20 and ROR:1256), which suggests a higher risk for causing RMS. The literature search revealed the involvement of the MRGPRX2 gene in the development of RMS. PHARMIP study unearthed Carbonic anhydrase II (CA2) as the common off-label target among the drugs causing RMS. The results obtained from molecular docking studies reinforced the findings as mentioned earlier, wherein the highest docking score was disinterred for oritavancin (−9.4 for MRGPRX2 and − 8.7 for CA2). What is new and conclusion Many antibiotics and other classes of medications have been discovered in the quest for drugs that may induce RMS, although a causal relationship could not be established. The implication of MRGPX2 and CA2 in the initial stages of pathogenesis necessitates the development of inhibitors that could be used as potential therapeutic agents against RMS. View on Web

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Assessing masticatory performance with a color mixing‐ability test using smartphone camera images

alexandrossfakianakis shared this article with you from Inoreader Assessing masticatory performance with a color mixing‐ability test using smartphone camera images via Journal of Oral Rehabilitation Abstract Background Color-mixing ability tests are frequently used to assess masticatory performance but the image acquisition process may be cumbersome and technique sensitive. Objectives To evaluate the reliability of smartphone camera images in assessing masticatory performance using a color-mixing ability test. Methods Participants were recruited into three groups of dental state (n=20 each): fully dentate, removable partial denture wearers and complete denture wearers. After performing a color-mixing ability test, images of the gum specimens (Hue-Check Gum©) were captured with two smartphones and compared with the images obtained from a flat-bed scanner by two examiners. The images were analyzed with a subjective- (SA) and an opto-electronical assessment (VoH). Inter- and intra-rater reliability were tested. ANOVA models with repeated measures were used for statistical analysis (⍺=0.05). Results All three image acquisition techniques were able to distinguish masticatory performance between different dental states. For SA, intra-rater reliability was slight to moderate and inter-rater reliability was substantial to almost perfect. For VoH, intra-rater reliability with the smartphones were significantly different between two examiners, but the inter-rater assessment was reliable. The opto-electronic analysis with smartphone images underestimated the masticatory performance significantly when compared to the flat-bed scanner analysis. Seven-day ageing of the specimens did not significantly affect the results. Conclusions The assessment of masticatory performance with the Hue-Check Gum© is a reliable method. The use of smartphones may occasionally underestimate masticatory performance; image acquisition with a flatbed scanner remains the gold standard. A centralized analysis of the photographed wafer may foster the reliability of the diagnosis. View on Web

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Effects of anterior bite planes fabricated from acrylic resin and thermoplastic material on masticatory muscle responses and maximum bite force in children with a deep bite: a 6‐month randomized controlled trial

alexandrossfakianakis shared this article with you from Inoreader Effects of anterior bite planes fabricated from acrylic resin and thermoplastic material on masticatory muscle responses and maximum bite force in children with a deep bite: a 6‐month randomized controlled trial via Journal of Oral Rehabilitation Abstract Background Anterior bite planes are bite-raising appliances used for deep bite correction. However, muscle responses to anterior bite planes of different hardnesses may vary. Objectives To prospectively evaluate masticatory muscle activity, muscle balance, and maximum bite force (MBF) responses to anterior bite planes fabricated from acrylic resin (ABP) or bi-laminate thermoplastic (TBP) over 6 months in children with a deep bite. Methods Sixty-six children were randomly assigned to the ABP, TBP, or untreated control groups. Masticatory muscle activity, activity index (AC), and percentage overlapping coefficient (POC) were assessed by surface electromyography; MBF, using a custom-made bite force sensor. Data were collected before, immediately after appliance insertion, and after 2 weeks and 1, 3, and 6 months of treatment. Within- and between-group differences were analyzed using one-way ANOVA/Kruskal-Wallis and Mann Whitney U-tests (α=0.05); Friedman's tests were used to assess within-group differences over time (α=0.08). Results At rest, no dependent variables changed throughout the study. At maximum clenching, masticatory muscle activity immediately dropped significantly but returned to baseline values and was equal to the control group at 1-3 months. The ABP group had significantly lower masseter activity and AC than the TBP group after insertion. Neither POC nor MBF were significantly different within or between groups. Conclusion Masticatory muscle activity reduced after anterior bite plane insertion but returned to baseline after 1-3 months. Masseter activity decreased significantly more in the ABP group than TBP group. Neither appliance significantly affected POC or MBF. View on Web

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Shared Decision-Making Concerning Anal Cancer Screening in Persons with HIV

alexandrossfakianakis shared this article with you from Inoreader Shared Decision-Making Concerning Anal Cancer Screening in Persons with HIV via Clinical Infectious Diseases Advance Access Abstract Background Anal high-grade squamous intraepithelial lesion (aHSIL) is the immediate precursor of anal cancer. Anal cytology is a recommended screening test to identify aHSIL among people with HIV (PWH). Heterogeneity of risk for invasive anal cancer among PWH suggests the value of a shared decision-making framework regarding screening. Methods Using a longitudinal HIV cohort with a comprehensive anal cancer screening program, we estimated the adjusted probabilities of having aHSIL on the first anal cytology. We used logistic regression models with inverse-probability weighting to account for differential screening in the cohort and to construct a predicted probability nomogram for aHSIL. Sensitivity analysis was performed to estimate aHSIL prevalence corrected for misclassification bias. Results Of 8139 PWH under care between 2007 and 2020, 4105 (49.8%) underwent at least one anal cytology test. First-time cytology aHS IL was present in 502 (12.2%) PWH. The adjusted probability of having aHSIL varied from 5% to 18% depending on patient characteristics. Prespecified factors in the aHSIL prediction model included nadir CD4 cell count, ethnicity, race, age, sex, gender identity, and HIV risk factors. The ability of the model to discriminate cytological aHSIL was modest, with an area under the curve (AUC) of 0.63 (95% CI%: 0.60-0.65). Conclusion PWH are at increased risk for aHSIL and invasive anal cancer. Risk, however, varies by patient characteristics. Individual risk factors profiles predictive of aHSIL can be modeled and operationalized as nomograms to facilitate shared decision-making conversations concerning anal cancer screening. View on Web

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Hospitalized patients with severe COVID-19 during the Omicron wave in Israel – benefits of a fourth vaccine dose

alexandrossfakianakis shared this article with you from Inoreader Hospitalized patients with severe COVID-19 during the Omicron wave in Israel – benefits of a fourth vaccine dose via Clinical Infectious Diseases Advance Access Abstract Background Waning vaccine-immunity and an increased incidence of COVID-19 during the Omicron outbreak led the Israeli Ministry of Health to recommend a fourth dose of BNT162b2 for high-risk individuals. This study assessed the effect of that dose for hospitalized patients with severe/critical, breakthrough COVID-19. Methods In this multi-center retrospective cohort study of hospitalized adults with severe/critical COVID-19 in Israel, from 01/15/2022–01/31/2022, cases were divided according to the number of vaccinations received. Poor outcome was defined as mechanical ventilation or in-hospital death, and was compared between 3- and 4-dose vaccinees using logistic regression. Results Included were 1,049 patients, median age 80 years (IQR 69-87), 51% males. Among them, 394 were unvaccinated, 386 had received 3 doses and 88 4 doses. The 3-dose group was older, had more males and immunosuppression, but with similar outco mes, 49% vs. 51% compared to unvaccinated patients (p = 0.72). Patients after 4 doses were similarly older and immunosuppressed, but had better outcomes compared to unvaccinated patients, 34% vs. 51% (p < 0.01). We examined independent predictors for poor outcome in patients with either 3 or 4 doses, received a median of 161 (IQR 147-168) or 14 (IQR 10-18) days before diagnosis, respectively. Receipt of the fourth dose was associated with protection: OR 0.51 (95%CI 0.3-0.87), as was Remdesivir OR 0.65 (95%CI 0.44-0.96). Male sex, chronic renal failure and dementia were associated with poor outcomes. Conclusions Among hospitalized patients with severe/critical breakthrough COVID-19, a recent fourth dose was associated with significant protection against mechanical ventilation or death, compared to three doses. View on Web

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Durability of immune responses after boosting in Ad26.COV2.S-primed healthcare workers

alexandrossfakianakis shared this article with you from Inoreader Durability of immune responses after boosting in Ad26.COV2.S-primed healthcare workers via Clinical Infectious Diseases Advance Access Abstract The emergence of SARS-CoV-2 variants raised questions regarding the durability of immune responses after homologous or heterologous booster vaccination after Ad26.COV2.S priming. We found that SARS-CoV-2-specific binding antibodies, neutralizing antibodies and T-cells are detectable 5 months after boosting, although waning of antibodies and limited cross-reactivity with Omicron BA.1 was observed. View on Web

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Association between Clostridium innocuum and antibiotic-associated diarrhea in adults and children: A cross-sectional study and comparative genomics analysis

alexandrossfakianakis shared this article with you from Inoreader Association between Clostridium innocuum and antibiotic-associated diarrhea in adults and children: A cross-sectional study and comparative genomics analysis via Clinical Infectious Diseases Advance Access Abstract Background A recent study from Taiwan suggested that Clostridium innocuum may be an unrecognized cause of antibiotic-associated diarrhea (AAD) and clinically indistinguishable from C. difficile infection. Our objective was to compare C. innocuum prevalence and strain between those with AAD and asymptomatic controls. Methods In this cross-sectional study, we collected stool from 200 individuals with AAD and 100 asymptomatic controls. We evaluated the association between AAD and C. innocuum in stool using anaerobic culture and qPCR. To identify strain-specific associations with AAD, we performed whole genome sequencing of C. innocuum isolates using Illumina MiSeq and constructed comparative genomics analyses. Results C. innocuum was isolated from stool of 126/300 (42%) subjects and more frequently from asymptomatic controls than AAD subjects (50/100 [50%] vs. 76/200 [38%], respectively; p = 0.047). C. innocuum isolation frequency was not associated with AAD in either the adult or pediatric subgroups. C. innocuum and C. difficile were frequently co-prevalent in individuals with and without diarrhea. There were no phylogenetic differences or accessory genome associations between C. innocuum isolates from AAD subjects and asymptomatic controls. Conclusion C. innocuum was frequently isolated and at a greater frequency in asymptomatic controls than those with AAD. We did not identify strain lineages or accessory genomic elements associated with AAD. These dat a highlight that differentiating C. innocuum-associated diarrhea from asymptomatic colonization, and differentiating diarrhea caused by C. difficile from C. innocuum, are clinical microbiology challenges that require additional investigation to identify host-specific factors and/or biomarkers that distinguish these conditions. View on Web

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Pharmacokinetic-pharmacodynamic determinants of clinical outcomes for rifampin-resistant tuberculosis: a multi-site prospective cohort study

alexandrossfakianakis shared this article with you from Inoreader Pharmacokinetic-pharmacodynamic determinants of clinical outcomes for rifampin-resistant tuberculosis: a multi-site prospective cohort study via Clinical Infectious Diseases Advance Access Abstract Background Treatment of rifampin-resistant and/or multidrug-resistant tuberculosis (RR/MDR-TB) requires multiple drugs and outcomes remain suboptimal. Some drugs are associated with improved outcome, however whether particular pharmacokinetic-pharmacodynamic relationships predict outcome is unknown. Methods Adults with pulmonary RR/MDR-TB in Tanzania, Bangladesh and Russian Federation receiving therapy with local regimens were enrolled from June, 2016 to July, 2018. Serum was collected after two, four, and eight weeks for each drug's area under the concentration-time curve (AUC0-24) and quantitative susceptibility of the Mycobacterium tuberculosis isolate measured by minimum inhibitory concentrations (MIC). Individual drug AUC0-24/MIC targets were assessed by adjusted odds ratios (OR) for association with favorable treatment outcome and hazard ratios (HR) for time to sputum culture conversion. K-means clustering algorithm separated the cohort of the most common multidrug regimen into four clusters by AUC0-24/MIC exposures. Results Among 290 patients, 62 (21%) experienced treatment failure, including 30 deaths. Moxifloxacin AUC0-24/MIC target of 58 was associated with favorable treatment outcome [OR 3.75 (1.21, 11.56), p = 0·022], while levofloxacin AUC0-24/MIC of 118.3, clofazimine AUC0-24/MIC of 50.5, and pyrazinamide AUC0-24 of 379 mg*h/L were associated with faster culture conversion [HR > 1·0, p < 0.05]. Other individual drug exposures were not predictive. Clustering by AUC0-24/MIC revealed those with lowest multidrug exposures had slowest culture conversion. Conclusion Amidst multidrug regimens for RR/MDR-TB, serum pharmacokinetics and M. tuberculosis MICs were variable, yet defined parameters to c ertain drugs – fluoroquinolones, pyrazinamide, clofazimine – were predictive and should be optimized to improve clinical outcome. View on Web

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Transmission blocking activity of low dose tafenoquine in healthy volunteers experimentally infected with Plasmodium falciparum

alexandrossfakianakis shared this article with you from Inoreader Transmission blocking activity of low dose tafenoquine in healthy volunteers experimentally infected with Plasmodium falciparum via Clinical Infectious Diseases Advance Access Abstract Background Blocking the transmission of parasites from humans to mosquitoes is a key component of malaria control. Tafenoquine exhibits activity against all stages of the malaria parasite and may have utility as a transmission blocking agent. We aimed to characterize the transmission blocking activity of low dose tafenoquine. Methods Healthy adults were inoculated with P. falciparum 3D7-infected erythrocytes on day 0. Piperaquine was administered on days 9 and 11 to clear asexual parasitemia while allowing gametocyte development. A single 50 mg oral dose of tafenoquine was administered on day 25. Transmission was determined by enriched membrane feeding assays pre-dose and at 1, 4 and 7 days post-dose. Artemether-lumefantrine was administered following the final assay. Outcomes were the reduction in mosquito infection and gametocytemia post-tafenoquine, and safety parameters. Results Six participants were enrolled, and all were infective to mosquitoes pre-tafenoquine, with a median 86% (range: 22–98) of mosquitoes positive for oocysts and 57% (range: 4–92) positive for sporozoites. By day 4 post-tafenoquine, the oocyst and sporozoite positivity rate had reduced by a median 35% (IQR: 16–46) and 52% (IQR: 40–62), respectively, and by day 7, 81% (IQR 36–92) and 77% (IQR 52–98), respectively. The decline in gametocyte density post-tafenoquine was not significant. No significant participant safety concerns were identified. Conclusion Low dose tafenoquine (50 mg) reduces P. falciparum transmission to mosquitoes, with a delay in effect. View on Web

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