Checkpoint blockade and BRAF/MEK therapy in the therapeutic setting improved the overall survival after sentinel node biopsy – a retrospective study comparing patients with primary care between 1998‐2009 and 2010‐2017

AlexandrosSfakianakis shared this article with you from Inoreader Checkpoint blockade and BRAF/MEK therapy in the therapeutic setting improved the overall survival after sentinel node biopsy – a retrospective study comparing patients with primary care between 1998‐2009 and 2010‐2017 via International Journal of Cancer Abstract Immunotherapies using checkpoint blockade and BRAF/MEK therapies have improved overall survival (OS) in patients with unresectable melanoma metastases. In this retrospective study, we aimed to demonstrate the resulting increase in melanoma-specific survival (MSS) and OS after the excision of primary melanomas (≥1 mm thick) and sentinel lymph node (SN) biopsy (SNB). Using Kaplan - Meier estimates and Cox models, we compared two consecutive cohorts. Patients in cohort 1 (N = 518) underwent SNB between 1998 and 2009, and patients in cohort 2 (N = 460) between 2010 and 2017, when checkpoint blockade and BRAF/ (MEK) inhibition became available for the treatment of unresectable relapses. The median follow-up times were 120 months and 73 months, respectively. While recurrence-free and distant metastasis-free survival rates remained very similar, MSS and OS increased in favor of cohort 2. The estimated 5-year OS rate of SN-positive patients increased by 14.3% (78.5% vs 64.2%, logrank test: P=0.005). The MSS benefit was significant even with low SN tumor burden (metastasis diameter <1 mm). On multivariate analyses, the risk-reduction in favor of cohort 2 was significant in the total population and in the SN-negative and SN-positive subgroups. In SN-positive patients, besides the availability of modern therapies, SN metastasis diameter, and ulceration were independent factors of MSS and OS. Treatment of unresectable melanoma recurrences with modern drug therapies results in significantly higher survival rates in a population with SNB. The survival benefit measured from primary melanoma affects both the SN-positive and SN-negative subpopulations. This article is protected by copyright. All rights reserved. View on Web

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Efficacy of adjunctive measures in peri‐implant mucositis. A systematic review and meta‐analysis

AlexandrosSfakianakis shared this article with you from Inoreader Efficacy of adjunctive measures in peri‐implant mucositis. A systematic review and meta‐analysis via Journal of Clinical Periodontology Abstract Aim To answer the following PICO question: In systemically healthy humans with peri-implant mucositis (PiM), what is the efficacy of patient-performed or administered (by prescription) measures used adjunctively to submarginal instrumentation, as compared to submarginal instrumentation alone or combined with a negative control, in terms of reducing bleeding on probing (BOP), in randomized controlled clinical trials (RCTs) with at least 3-month follow-up? Material and methods Three databases were searched until April 2022. Weighted mean differences (WMD) with 95% confidence intervals (CIs) and predictive intervals were calculated. Results 16 parallel RCTs corresponding to 14 studies with low/moderate risk of bias were included. Test groups showed greater reductions in BOP (%) than control groups (nstudies=16; npatients=650; WMD=14.25%; 95% CI [9.06; 19.45]; p<0.001; I2=98.7%). The greatest WMD in BOP reductions (%) were obtained by antiseptics (ns=5; np=229; WMD=22.72%; 95% CI [19.40; 26.04]; p<0.001; I2=94.8%), followed by probiotics (ns=6; np=260; WMD=12.11%; 95% CI [3.20; 21.03]; p=0.008; I2=93.3%), and systemic antibiotics (ns=3; np=101; WMD=5.97%; 95% CI [1.34; 10.59]; p=0.012; I2=58.1%). Disease resolution was scarcely reported (n=6). Conclusions Significant clinical improvements can be obtained when professional submarginal instrumentation is combined with patient-performed or administered (by prescription) adjunctive measures, although a complete disease resolution may not be achieved. View on Web

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Embolization in Juvenile Nasopharyngeal Angiofibroma Surgery: A Systematic Review and Meta‐Analysis

AlexandrosSfakianakis shared this article with you from Inoreader Embolization in Juvenile Nasopharyngeal Angiofibroma Surgery: A Systematic Review and Meta‐Analysis via The Laryngoscope How are clinical outcomes of juvenile nasopharyngeal angiofibroma (JNA) resection affected by preoperative embolization and the type of embolization used? In this systematic review and meta-analysis, the use of preoperative embolization was shown to decrease blood loss during JNA resection and direct embolization provided improved recurrence and complication rates compared to transarterial embolization. Preoperative direct puncture embolization in JNA resection may reduce intraoperative and postoperative complications. Objective To compare outcomes of juvenile nasopharyngeal angiofibroma (JNA) resection between embolized and non-embolized cohorts, and between transarterial embolization (TAE) and direct puncture embolization (DPE). Data Sources Per PRISMA guidelines, PubMed, Embase, Web of Science, Scopus, and Cochrane databases were searched for publications prior to or in 2021. Materials and Methods Original English manuscripts investigating the resection of JNA with and without preoperative embolization were included. Embolization type, recurrence rate, complication rates, blood loss, and transfusions were extracted. Risk of bias was assessed by the Risk of Bias in Non-randomized Studies—of Interventions method. Results There were 61 studies with 917 patients included. Preoperative embolization was performed in 79.3% of patients. Of those embolized, 75.8% (N = 551) underwent TAE and 15.8% (N = 115) underwent DPE. JNA recurrence in embolized patients was lower than in non-embolized patients (9.3% vs. 14.4%; odds ratio [OR]: 0.61, 95% confidence interval [CI]: 0.35, 1.06). DPE resulted in lower rates of disease recurrence (0% vs. 9.5%; OR: 0.066, 95% CI: 0.016, 0.272) and complications (1.8% vs. 21.9%; OR: 0.07, 95% CI: 0.02, 0.3) than TAE. A random effects Bayesian model was performed to analyze the difference in mean blood loss in 6 studies that included both embolized and non-embolized patients. This analysis showed a mean reduction in blood loss of 798 mL in the embolized group. Conclusions We found embolization decreases blood loss in JNA resection. DPE led to improved recurrence and complication rates when compared to TAE, but future prospective studies are needed to further evaluate which embolization technique can optimize outcomes in JNA. Level of Evidence NA Laryngoscope, 2023 View on Web

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Onychomycosis associated with diabetic foot syndrome: a systematic review

AlexandrosSfakianakis shared this article with you from Inoreader Onychomycosis associated with diabetic foot syndrome: a systematic review via Mycoses Abstract Background A systematic review was conducted to investigate the prevalence of onychomycosis in patients with diabetes. The association of onychomycosis with risk factors in patients with diabetic foot syndrome was also examined. Methods The recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist were applied, and the included studies were assessed using the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) method. Searches were conducted in October 2022 using PubMed (Medline) and Scopus for clinical studies, clinical trials, comparative studies, observational studies, and randomised clinical trials or controlled clinical trials addressing the prevalence and consequences of onychomycosis in patients with diabetes, diagnoses, or treatments. Two authors performed the study selection and data extraction, and any discrepancies between the two reviewers were resolved through discussion with a third reviewer. Results The systematic review included nine studies that met the inclusion criteria, and these studies enrolled 5426 patients with diabetes. Among these patients, 28.55% had onychomycosis that was mainly caused by Trichophyton rubrum. A significant association was found between the occurrence of onychomycosis and the presence of diabetic neuropathy (p=0.012) and elevated glycosylated haemoglobin values (p=0.039). There was no significant association between onychomycosis and ulceration (p=0.185). Eight studies had a grade 4 level of evidence and a grade C recommendation, and one study had a grade 1b level of evidence and a grade A recommendation. Conclusion The information described in the literature is insufficient and heterogeneous regarding the association of risk factors and ulceration in patients with diabetic foot compared with developing onychomycosis. There is also a need to implement onychomycosis diagnostic testing instead of relying only on a clinical diagnosis. Additional prospective, randomised, comparative studies are needed to increase the quality of studies in the literature. View on Web

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PPAR-γ activation promotes xenogenic bioroot regeneration by attenuating the xenograft induced-oxidative stress

AlexandrosSfakianakis shared this article with you from Inoreader PPAR-γ activation promotes xenogenic bioroot regeneration by attenuating the xenograft induced-oxidative stress via International Journal of Oral Science - Issue International Journal of Oral Science, Published online: 16 February 2023; doi:10.1038/s41368-023-00217-4 PPAR-γ activation promotes xenogenic bioroot regeneration by attenuating the xenograft induced-oxidative stress View on Web

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In vivo PIWI slicing in mouse testes deviates from rules established in vitro [LETTER TO THE EDITOR]

AlexandrosSfakianakis shared this article with you from Inoreader In vivo PIWI slicing in mouse testes deviates from rules established in vitro [LETTER TO THE EDITOR] via RNA current issue Argonautes are small RNA-binding proteins, with some having small RNA-guided endonuclease (slicer) activity that cleaves target nucleic acids. One cardinal rule that is structurally defined is the inability of slicers to cleave target RNAs when nucleotide mismatches exist between the paired small RNA and the target at the cleavage site. Animal-specific PIWI clade Argonautes associate with PIWI-interacting RNAs (piRNAs) to silence transposable elements in the gonads, and this is essential for fertility. We previously demonstrated that purified endogenous mouse MIWI fails to cleave mismatched targets in vitro. Surprisingly, here we find using knock-in mouse models that target sites with cleavage-site mismatches at the 10th and 11th piRNA nucleotides are precisely sliced in vivo. This is identical to the slicing outcome in knock-in mice where targets are base-paired perfectly with the piRNA. Additionally, we find that pachytene piRNA-guided slicing in both these situations failed to initiate phased piRNA production from the specific target mRNA we studied. Instead, the two slicer cleavage fragments were retained in PIWI proteins as pre-piRNA and 17–19 nt by-product fragments. Our results indicate that PIWI slicing rules established in vitro are not respected in vivo, and that all targets of PIWI slicing are not substrates for piRNA biogenesis. View on Web

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RNA:RNA interaction in ternary complexes resolved by chemical probing [ARTICLE]

AlexandrosSfakianakis shared this article with you from Inoreader RNA:RNA interaction in ternary complexes resolved by chemical probing [ARTICLE] via RNA current issue RNA regulation can be performed by a second targeting RNA molecule, such as in the microRNA regulation mechanism. Selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) probes the structure of RNA molecules and can resolve RNA:protein interactions, but RNA:RNA interactions have not yet been addressed with this technique. Here, we apply SHAPE to investigate RNA-mediated binding processes in RNA:RNA and RNA:RNA-RBP complexes. We use RNA:RNA binding by SHAPE (RABS) to investigate microRNA-34a (miR-34a) binding its mRNA target, the silent information regulator 1 (mSIRT1), both with and without the Argonaute protein, constituting the RNA-induced silencing complex (RISC). We show that the seed of the mRNA target must be bound to the microRNA loaded into RISC to enable further binding of the compensatory region by RISC, while the naked miR-34a is able to bind the compensatory region without seed interaction. The method presented here provi des complementary structural evidence for the commonly performed luciferase-assay-based evaluation of microRNA binding-site efficiency and specificity on the mRNA target site and could therefore be used in conjunction with it. The method can be applied to any nucleic acid-mediated RNA- or RBP-binding process, such as splicing, antisense RNA binding, or regulation by RISC, providing important insight into the targeted RNA structure. View on Web

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Z-RNA biology: a central role in the innate immune response? [MINI-REVIEW]

AlexandrosSfakianakis shared this article with you from Inoreader Z-RNA biology: a central role in the innate immune response? [MINI-REVIEW] via RNA current issue Z-RNA is a higher-energy, left-handed conformation of RNA, whose function has remained elusive. A growing body of work alludes to regulatory roles for Z-RNA in the immune response. Here, we review how Z-RNA features present in cellular RNAs—especially containing retroelements—could be recognized by a family of winged helix proteins, with an impact on host defense. We also discuss how mutations to specific Z-contacting amino acids disrupt their ability to stabilize Z-RNA, resulting in functional losses. We end by highlighting knowledge gaps in the field, which, if addressed, would significantly advance this active area of research. View on Web

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Designing a Prolonged Method of Therapeutic Delivery to Support Rehabilitation From Ototoxic Damage in a Schwann Cell Model

AlexandrosSfakianakis shared this article with you from Inoreader Designing a Prolonged Method of Therapeutic Delivery to Support Rehabilitation From Ototoxic Damage in a Schwann Cell Model via Otology & Neurotology - Published Ahead-of-Print Hypothesis The ototoxicity of gentamicin and cisplatin can be evaluated with a Schwann cell model to screen for otoprotective agents that can be encapsulated into poly (lactic-co-glycolic acid) (PLGA) microparticles for drug delivery to the inner ear. Background Aminoglycosides and cisplatin are widely prescribed but known to cause ototoxicity. There is strong evidence that compromise to Schwann cells ensheathing inner ear afferent neurons results in inner ear dysfunction mimicking drug-induced ototoxicity. There is a need for a model for ototoxic demyelination to screen medications for protective potential and to subsequently target and tune the delivery of any promising agents. Methods RT4-D6P2T rat schwannoma cells were used as a Schwann cell model to assess gentamicin and cisplatin toxicity and to screen for protective agents. Cell viability was evaluated with the MTT cell proliferation assay. N-acetylcysteine (NAC) was encapsulated into a PLGA microparticle, and its elution profile was determined. Results The estimated 50% lethal concentration dose for gentamicin was 805.6 μM, which was 46-fold higher than that for cisplatin (17.5 μM). In several trials, cells dosed with NAC and cisplatin demonstrated a 22.6% (p View on Web

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Motor Imagery EEG Decoding Based on Multi-Scale Hybrid Networks and Feature Enhancement

AlexandrosSfakianakis shared this article with you from Inoreader Motor Imagery EEG Decoding Based on Multi-Scale Hybrid Networks and Feature Enhancement via Neural Systems and Rehabilitation Engineering, IEEE Transactions on - new TOC Motor Imagery (MI) based on Electroencephalography (EEG), a typical Brain-Computer Interface (BCI) paradigm, can communicate with external devices according to the brain's intentions. Convolutional Neural Networks (CNN) are gradually used for EEG classification tasks and have achieved satisfactory performance. However, most CNN-based methods employ a single convolution mode and a convolution kernel size, which cannot extract multi-scale advanced temporal and spatial features efficiently. What's more, they hinder the further improvement of the classification accuracy of MI-EEG signals. This paper proposes a novel Multi-Scale Hybrid Convolutional Neural Network (MSHCNN) for MI-EEG signal decoding to improve classification performance. The two-dimensional convolution is used to extract temporal and spatial features of EEG signals and the one-dimensional convolution is used to extract advanced temporal features of EEG signals. In addition, a channel coding method is proposed to improve the expression capacity of the spatiotemporal characteristics of EEG signals. We evaluate the performance of the proposed method on the dataset collected in the laboratory and BCI competition IV 2b, 2a, and the average accuracy is at 96.87%, 85.25%, and 84.86%, respectively. Compared with other advanced methods, our proposed method achieves higher classification accuracy. Then we use the proposed method for an online experiment and design an intelligent artificial limb control system. The proposed method effectively extracts EEG signals' advanced temporal and spatial features. Additionally, we design an online recognition system, which contributes to the further development of the BCI system. View on Web

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