Πέμπτη 16 Φεβρουαρίου 2023

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

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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.

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Operation early‐bird: Investigating altered light exposure in military barracks on sleep and performance—a placebo‐controlled study

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Summary

The manipulation of light exposure in the evening has been shown to modulate sleep, and may be beneficial in a military setting where sleep is reported to be problematic. This study investigated the efficacy of low-temperature lighting on objective sleep measures and physical performance in military trainees. Sixty-four officer-trainees (52 male/12 female, mean ± SD age: 25 ± 5 years) wore wrist-actigraphs for 6 weeks during military training to quantify sleep metrics. Trainee 2.4-km run time and upper-body muscular-endurance were assessed before and after the training course. Participants were randomly assigned to either: low-temperature lighting (LOW, n = 19), standard-temperature lighting with a placebo "sleep-enhancing" device (PLA, n = 17), or standard-temperature lighting (CON, n = 28) groups in their military barracks for the duration of the course. Repeated-measures ANOVAs were run to identify significant differences with post hoc ana lyses and effect size calculations performed where indicated. No significant interaction effect was observed for the sleep metrics; however, there was a significant effect of time for average sleep duration, and small benefits of LOW when compared with CON (d = 0.41–0.44). A significant interaction was observed for the 2.4-km run, with the improvement in LOW (Δ92.3 s) associated with a large improvement when compared with CON (Δ35.9 s; p = 0.003; d = 0.95 ± 0.60), but not PLA (Δ68.6 s). Similarly, curl-up improvement resulted in a moderate effect in favour of LOW (Δ14 repetitions) compared with CON (Δ6; p = 0.063; d = 0.68 ± 0.72). Chronic exposure to low-temperature lighting was associated with benefits to aerobic fitness across a 6-week training period, with minimal effects on sleep measures.
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Autophagy and its role in osteosarcoma

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Autophagy and its role in osteosarcoma

In this review, we summarized the role of autophagy in OS proliferation, metastasis, chemotherapy, radiotherapy, and immunotherapy. And we think that autophagy-related genes and pathways could serve as potential targets for OS therapy.


Abstract

Osteosarcoma (OS) is the most common bone malignancy and preferably occurs in children and adolescents. Despite significant advances in surgery and chemotherapy for OS over the past few years, overall survival rates of OS have reached a bottleneck. Thus, extensive researches aimed at developing new therapeutic targets for OS are urgently needed. Autophagy, a conserved process which allows cells to recycle altered or unused organelles and cellular components, has been proven to play a critical role in multiple biological processes in OS. In this article, we summarized the association between autophagy and proliferation, metastasis, chemotherapy, radiotherapy, and immunotherapy of OS, revealing that autophagy-related genes and pathways could serve as potential targets for OS therapy.
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Embolization in Juvenile Nasopharyngeal Angiofibroma Surgery: A Systematic Review and Meta‐Analysis

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

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
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Onychomycosis associated with diabetic foot syndrome: a systematic review

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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.
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Risky business: Understanding the association between objective COVID‐19 occupational risk features and worker subjective risk perceptions

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Abstract

Many workers are at risk of contracting COVID-19 through work, and subjective perceptions of COVID-19 risk are important predictors of worker attitudes and behaviours. However, little to no research provides comprehensive examination of objective COVID-19 occupational risk factors and how, or under what conditions, these factors relate to subjective risk perceptions. Using two wave survey data matched with archival data from the Occupational Information Network (O*Net) and county-level COVID-19 case data (N = 295), we examine how objective COVID-19 occupational risk relates to workers' subjective risk of contracting COVID-19 at work. We also examine the moderating roles of financial frailty, adherence to governmental workplace safety recommendations, and local COVID-19 threat. Results indicate that objective COVID-19 occupational risk significantly predicts subjective risk of contracting COVID-19 at work. Moreover, factors representing in-person work conducted in close proximity to others accounted for a large proportion of explained variance in subjective risk. There was no support for moderation; however, financial frailty and workplace safety had independent main effects on subjective risk perceptions. Our results have theoretical implications for the Economic Stress and COVID-19 Occupational Risk model (Sinclair et al., Appl. Psychol., 70, 2021, 85), individual models of subjective risk perceptions, and practical implications for mitigating occupational risk at work.
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PPAR-γ activation promotes xenogenic bioroot regeneration by attenuating the xenograft induced-oxidative stress

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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
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RGS12 represses oral squamous cell carcinoma by driving M1 polarization of tumor-associated macrophages via controlling ciliary MYCBP2/KIF2A signaling

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International Journal of Oral Science, Published online: 16 February 2023; doi:10.1038/s41368-023-00216-5

RGS12 represses oral squamous cell carcinoma by driving M1 polarization of tumor-associated macrophages via controlling ciliary MYCBP2/KIF2A signaling
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RNA:RNA interaction in ternary complexes resolved by chemical probing [ARTICLE]

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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.
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Specific mechanisms of translation initiation in higher eukaryotes: the eIF4G2 story [REVIEW]

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The eukaryotic initiation factor 4G2 (eIF4G2, DAP5, Nat1, p97) was discovered in 1997. Over the past two decades, dozens of papers have presented contradictory data on eIF4G2 function. Since its identification, eIF4G2 has been assumed to participate in noncanonical translation initiation mechanisms, but recent results indicate that it can be involved in scanning as well. In particular, eIF4G2 provides leaky scanning through some upstream open reading frames (uORFs), which are typical for long 5' UTRs of mRNAs from higher eukaryotes. It is likely the protein can also help the ribosome overcome other impediments during scanning of the 5' UTRs of animal mRNAs. This may explain the need for eIF4G2 in higher eukaryotes, as many mRNAs that encode regulatory proteins have rather long and highly structured 5' UTRs. Additionally, they often bind to various proteins, which also hamper the movement of scanning ribosomes. This review discusses the suggested mechanisms of eIF4G2 action, denote s obscure or inconsistent results, and proposes ways to uncover other fundamental mechanisms in which this important protein factor may be involved in higher eukaryotes.
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