Parkinson's disease - The dentist's role as part of the healthcare team.

Parkinson's disease is a neurodegenerative disease that results in patients exhibiting uncontrolled movements, changes in saliva production, and difficulty in swallowing and speech. Understanding the staging of the disease and the available therapies allows dentists to treat these patients safely and with compassion to meet their oral health care needs for an optimal quality of life. This appraisal discusses Parkinson's disease as it relates to clinically relevant facts to manage and treat the oral health care needs of these patients in the short and long term including general dental care recommendations. Important observations related to Parkinson's disease include disease causation,; stages, pharmacologic treatment, the effects on saliva, mastication, dysphagia, and aspiration pneumonia. Dental recommendations are made for the dentate, the partially edentulous, and the completely edentulous Parkinson's patients with a focus on late-stage concerns. Optimizing dental health will help maintain the quality of life as the disease progresses. In late stages of Parkinson's disease, dental treatment should focus on keeping the patient comfortable and out of pain.  While benign neglect is an often-used term, compassionate therapy in the late stages of Parkinson's disease is a more compelling term for defining the patient's needs.  Since dysphagia in Parkinson's patients has been underdiagnosed, neurologists must be aware of the important part that dentists play in the early diagnosis for these patients.  Early referral to a dentist is vital to mitigate the unfortunate consequence of the need for extensive dental care in late-stage patients.

Comparing the effect of intermittent diazepam and continuous phenobarbital in preventing recurrent febrile seizures among children under 6 years old: A systematic review and meta-analysis.

Background: Febrile convulsion (FC) is the most common and preventable seizure in children. This study aimed to assess the effectiveness of the diazepam and phenobarbital for preventing recurrent FC. Materials and Methods: In this systematic review study, literature published in English language were carefully searched in biological databases (Cochrane Library, Medline, Scopus, CINHAL, Psycoinfo, and Proquest) by February 2020.Randomized clinical trials (RCTs) and Quasi randomized trial were included in the review. Two researchers checked the literature independently. The quality of studies was assessed using the JADAD score. The potential risk for publication bias was assessed by Funnel plot and Egger's test. Meta regression test and sensitivity analysis were used to identify the reasons for heterogeneity. Given the results of assessing heterogeneity, the random effect model in RevMan5.1 software was used for meta analysis. Results: Four out of 17 studies had compared the effect of diazepam and phenobarbital in preventing recurrent FC. The result of the meta analysis showed that the use of diazepam in comparison with phenobarbital reduces the risk of recurrence FC by 34% (risk ratio = 0.66, 95% confidence interval [CI] = [0.36-1.21]), but the relationship was not statistically significant. In assessing the effect of diazepam or phenobarbital versus placebo, the results showed that the use of diazepam and phenobarbital has reduced the risk of recurrent FC by 49% (risk ratio = 0.51, 95% CI = [0.32-0.79]) and 37% (risk ratio = 0.63, 95% CI = [0.42-0.96)]), respectively, and these relationships were statistically significant (P < 0.05). Results of the meta regression test showed that the follow up time can be a reason for the heterogeneity between trials with the comparison of diazepam versus phenobarbital (r = 0.047, P = 0.049) and Phenobarbital versus placebo (r = 0.022, P = 0.016). According to the results of Funnel plot and Egger's test, there was evidence of publication bias (P = 0.0584 for comparison of diazepam vs. phenobarbital; P = 0.0421 for comparison of diazepam vs. placebo; P = 0.0402 for comparison of phenobarbital vs. placebo). Conclusion: The results of this meta analysis indicated that preventive anticonvulsants can be useful in preventing recurrent convulsions in cases of febrile seizures.

Dormancy in Breast Cancer, the Role of Autophagy, lncRNAs, miRNAs and Exosomes.

Breast cancer (BC) is the most frequently diagnosed cancer in women for which numerous diagnostic and therapeutic options have been developed. Namely, the targeted treatment of BC, for the most part, relies on the expression of growth factors and hormone receptors by these cancer cells. Despite this, close to 30% of BC patients may experience relapse due to the presence of minimal residual disease (MRD) consisting of surviving disseminated tumour cells (DTCs) from the primary tumour which can colonise a secondary site. This can lead to either detectable metastasis or DTCs entering a dormant state for a prolonged period where they are undetectable. In the latter, cells can re-emerge from their dormant state due to intrinsic and microenvironmental cues leading to relapse and metastatic outgrowth. Pre- and clinical studies propose that targeting dormant DTCs may inhibit metastasis, but the choice between keeping them dormant or forcing their "awakening" is still controversial. This review will focus on cancer cells' microenvironmental cues and metabolic and molecular properties, which lead to dormancy, relapse, and metastatic latency in BC. Furthermore, we will focus on the role of autophagy, long non-coding RNAs (lncRNAs), miRNAs, and exosomes in influencing the induction of dormancy and awakening of dormant BC cells. In addition, we have analysed BC treatment from a viewpoint of autophagy, lncRNAs, miRNAs, and exosomes. We propose the targeted modulation of these processes and molecules as modern aspects of precision medicine for BC treatment, improving both novel and traditional BC treatment options. Understanding these pathways and processes may ultimately improve BC patient prognosis, patient survival, and treatment response.

Paediatric Burkitt lymphoma patient-derived xenografts capture disease characteristics over time and are a model for therapy.

Burkitt lymphoma (BL) accounts for almost two-thirds of all B-cell non-Hodgkin lymphoma (B-NHL) in children and adolescents and is characterised by a MYC translocation and rapid cell turnover. Intensive chemotherapeutic regimens have been developed in recent decades, including the lymphomes malins B (LMB) protocol, which have resulted in a survival rate in excess of 90%. Recent clinical trials have focused on immunochemotherapy, with the addition of rituximab to chemotherapeutic backbones, showing encouraging results. Despite these advances, relapse and refractory disease occurs in up to 10% of patients and salvage options for these carry a dismal prognosis. Efforts to better understand the molecular and functional characteristics driving relapse and refractory disease may help improve this prognosis. This study has established a paediatric BL patient-derived xenograft (PDX) resource which captures and maintains tumour heterogeneity, may be used to better characterise tumours and identify cell populations responsible for therapy resistance.

The Contribution of Autophagy and LncRNAs to MYC-Driven Gene Regulatory Networks in Cancers.

MYC is a target of the Wnt signalling pathway and governs numerous cellular and developmental programmes hijacked in cancers. The amplification of MYC is a frequently occurring genetic alteration in cancer genomes, and this transcription factor is implicated in metabolic reprogramming, cell death, and angiogenesis in cancers. In this review, we analyse MYC gene networks in solid cancers. We investigate the interaction of MYC with long non-coding RNAs (lncRNAs). Furthermore, we investigate the role of MYC regulatory networks in inducing changes to cellular processes, including autophagy and mitophagy. Finally, we review the interaction and mutual regulation between MYC and lncRNAs, and autophagic processes and analyse these networks as unexplored areas of targeting and manipulation for therapeutic gain in MYC-driven malignancies.

Diagnostic accuracy of circulating-free DNA for the determination of MYCN amplification status in advanced-stage neuroblastoma: a systematic review and meta-analysis.

BACKGROUND: MYCN amplification (MNA) is the strongest indicator of poor prognosis in neuroblastoma (NB). This meta-analysis aims to determine the diagnostic accuracy of MNA analysis in circulating-free DNA (cfDNA) from advanced-stage NB patients. METHODS: A systematic review of electronic databases was conducted to identify studies exploring the detection of MNA in plasma/serum cfDNA from NB patients at diagnosis using PCR methodology. Pooled estimates for sensitivity, specificity and diagnostic odds ratio (DOR) were calculated by conducting a bivariate/HSROC random-effects meta-analysis. RESULTS: Seven studies, with a total of 529 advanced-stage patients, were eligible. The pooled sensitivity of cfDNA-based MNA analysis was 0.908 (95% CI, 0.818-0.956), the pooled specificity was 0.976 (0.940-0.991) and the DOR was 410.0 (-103.6 to 923.7). Sub-grouped by INSS stage, the sensitivity for stage 3 and 4 patients was 0.832 (0.677-0.921) and 0.930 (0.834-0.972), respectively. The specificity was 0.999 (0.109-1.000) and 0.974 (0.937-0.990), respectively, and the DOR was 7855.2 (-66267.0 to 81977.4) and 508.7 (-85.8 to 1103.2), respectively. CONCLUSIONS: MNA analysis in cfDNA using PCR methodology represents a non-invasive approach to rapidly and accurately determine MNA status in patients with advanced-stage NB. Standardised methodology must be developed before this diagnostic test can enter the clinic.

The AP-1 transcription factor component Fosl2 potentiates the rate of myocardial differentiation from the zebrafish second heart field.

The vertebrate heart forms through successive phases of cardiomyocyte differentiation. Initially, cardiomyocytes derived from first heart field (FHF) progenitors assemble the linear heart tube. Thereafter, second heart field (SHF) progenitors differentiate into cardiomyocytes that are accreted to the poles of the heart tube over a well-defined developmental window. Although heart tube elongation deficiencies lead to life-threatening congenital heart defects, the variables controlling the initiation, rate and duration of myocardial accretion remain obscure. Here, we demonstrate that the AP-1 transcription factor, Fos-like antigen 2 (Fosl2), potentiates the rate of myocardial accretion from the zebrafish SHF. fosl2 mutants initiate accretion appropriately, but cardiomyocyte production is sluggish, resulting in a ventricular deficit coupled with an accumulation of SHF progenitors. Surprisingly, mutant embryos eventually correct the myocardial deficit by extending the accretion window. Overexpression of Fosl2 also compromises production of SHF-derived ventricular cardiomyocytes, a phenotype that is consistent with precocious depletion of the progenitor pool. Our data implicate Fosl2 in promoting the progenitor to cardiomyocyte transition and uncover the existence of regulatory mechanisms to ensure appropriate SHF-mediated cardiomyocyte contribution irrespective of embryonic stage.

Management of Amelogenesis Imperfecta in Adolescent Patients: Clinical Report.

The oral rehabilitation of adolescent patients with amelogenesis imperfecta (AI) is complex due to the presence of mixed dentition with altered eruption sequence. In this article, the interdisciplinary treatment approach for adolescent patients with AI is discussed. The types and timing of treatments at various stages of growth are described through a literature review on this topic. AI is an inherited condition that disturbs the development of the enamel structure. Because of the presence of mixed dentition, definitive treatment options often have to be delayed until eruption of permanent dentition is complete, requiring careful treatment coordination and proper sequencing between different dental disciplines starting at a young age. Adolescent patients require prosthodontic treatment design that can be adapted to the changes in arch shapes, sizes, interarch relationship, and esthetic needs. AI patients are often challenged with both excessive and limited restorative spaces within the same arch due to the abnormal growth patterns, enamel structure, tooth size, and tooth shape. Therefore, careful determination of the required restorative space is critical to ensure optimal prognosis. This clinical report discusses treatment recommendations, timing of various treatment modalities, and involvement of appropriate interdisciplinary teams for managing adolescent patients.

Student's Perception of the Impact of E-learning on Dental Education.

AIM: The aim of this study is to assess the influence of e-learning on dental education as perceived by predoctoral dental students. MATERIALS AND METHODS: In an institutional review board (IRB) approved protocol, a 14-question survey was created and electronically distributed to second-, third-, and fourth-year dental students. The participation was considered voluntary and all responses were anonymous. RESULTS: The survey targeted 1,130 predoctoral students, of which 255 (22.6%) responded. Of the respondents, 124 students (48.6%) preferred traditional lecture mixed with online learning, while 46 students (18%) preferred only the traditional lecture style. The top three electronic resources/applications, which students perceived as having the greatest impact on their learning, were: YouTube, Bone Box, and Google. The responses also indicated that 76.5% of the students gave high credibility (scores of 4 and 5) to electronic resources recommended by faculties. Sixty percent of students spent 1 to more than 4 hours per day on electronic resources for academic performance. The most important factor for online applications influencing academic performance was "organization and logic of content" (54%). E-learning had a significant perceived effect (scores of 4/5) on didactic understanding (65.1%) and on clinical understanding (71.4%). Students observed that faculties estimated to be under 50 years of age were more likely to incorporate e-learning into courses (52.6%) and more likely to use social media for communication (41.6%). CONCLUSION: The results indicate that e-learning may successfully be used in a dental school's curriculum to enhance students' perceptions of fundamental concepts and to enable students to apply this knowledge to clinical cases. CLINICAL SIGNIFICANCE: E-learning has recently been proposed as a basic supplementary tool to enhance medical and dental education. It is crucial to determine dental students' preferences regarding social media, online applications, and databases in order to incorporate e-learning into dental school courses.

Perceived barriers to methadone maintenance treatment among Iranian opioid users.

BACKGROUND: Opioid use is a severe problem in Iran. Despite methadone maintenance treatment (MMT) programs being one of the most important treatment strategies for reducing individual and public harms associated with opioid use, a large proportion of Iranian patients refuse to participate in such treatment programs. METHODS: The present study aims to explore the beliefs and attitudes toward MMT programs of opioid-dependent patients who were participating or had participated in methadone therapy. In-depth interviews were conducted with 23 opioid users between 27 and 58 years of age from Kurdistan provinces. RESULTS: Overall, six themes were discovered to be key barriers relating to methadone treatment, including financial barriers related to methadone treatment, lack of awareness about methadone treatment, negative attitudes regarding using methadone, worries about methadone's side effects, social stigma ascribed to methadone therapy, and systemic barriers to methadone treatment. CONCLUSION: Our study revealed that the cost of treatment is a major obstacle to attending and continuing at MMT programs and that addicts and their families are not always accurately informed about the duration of MMT programs and the side effects of methadone treatment.

Group 4 ITI Consensus Report: Risks and biologic complications associated with implant dentistry.

OBJECTIVES: The aim of Working Group 4 was to address topics related to biologic risks and complications associated with implant dentistry. Focused questions on (a) diagnosis of peri-implantitis, (b) complications associated with implants in augmented sites, (c) outcomes following treatment of peri-implantitis, and (d) implant therapy in geriatric patients and/or patients with systemic diseases were addressed. MATERIALS AND METHODS: Four systematic reviews formed the basis for discussion in Group 4. Participants developed statements and recommendations determined by group consensus based on the findings of the systematic reviews. These were then presented and accepted following further discussion and modifications as required by the plenary. RESULTS: Bleeding on probing (BOP) alone is insufficient for the diagnosis of peri-implantitis. The positive predictive value of BOP alone for the diagnosis of peri-implantitis varies and is dependent on the prevalence of peri-implantitis within the population. For patients with implants in augmented sites, the prevalence of peri-implantitis and implant loss is low over the medium to long term. Peri-implantitis treatment protocols which include individualized supportive care result in high survival of implants after 5 years with about three-quarters of implants still present. Advanced age alone is not a contraindication for implant therapy. Implant placement in patients with cancer receiving high-dose antiresorptive therapy is contraindicated due to the associated high risk for complications. CONCLUSIONS: Diagnosis of peri-implantitis requires the presence of BOP as well as progressive bone loss. Prevalence of peri-implantitis for implants in augmented sites is low. Peri-implantitis treatment should be followed by individualized supportive care. Implant therapy for geriatric patients is not contraindicated; however, comorbidities and autonomy should be considered.

Scan-layered reconstructions: A pilot study of a nondestructive dental histoanatomical analysis method and digital workflow to create restorations driven by natural dentin and enamel morphology.

OBJECTIVE: This work aims to present a pilot study of a non-destructive dental histo-anatomical analysis technique as well as to push the boundaries of the presently available restorative workflows for the fabrication of highly customized ceramic restorations. MATERIALS AND METHODS: An extracted human maxillary central incisor was subject to a micro computed tomography scan and the acquired data was transferred into a workstation, reconstructed, segmented, evaluated and later imported into a Computer-Aided Design/Computer-Aided Manufacturing software for the fabrication of a ceramic resin-bonded prosthesis. RESULTS: The obtained prosthesis presented an encouraging optical behavior and was used clinically as final restoration. CONCLUSION: The digitally layered restorative replication of natural tooth morphology presents today as a clear possibility. New clinical and laboratory-fabricated, biologically inspired digital restorative protocols are to be expected in the near future. CLINICAL SIGNIFICANCE: The digitally layered restorative replication of natural tooth morphology presents today as a clear possibility. This pilot study may represent a stimulus for future research and applications of digital imaging as well as digital restorative workflows in service of esthetic dentistry.

Zebrafish second heart field development relies on progenitor specification in anterior lateral plate mesoderm and nkx2.5 function.

Second heart field (SHF) progenitors perform essential functions during mammalian cardiogenesis. We recently identified a population of cardiac progenitor cells (CPCs) in zebrafish expressing latent TGFß-binding protein 3 (ltbp3) that exhibits several defining characteristics of the anterior SHF in mammals. However, ltbp3 transcripts are conspicuously absent in anterior lateral plate mesoderm (ALPM), where SHF progenitors are specified in higher vertebrates. Instead, ltbp3 expression initiates at the arterial pole of the developing heart tube. Because the mechanisms of cardiac development are conserved evolutionarily, we hypothesized that zebrafish SHF specification also occurs in the ALPM. To test this hypothesis, we Cre/loxP lineage traced gata4(+) and nkx2.5(+) ALPM populations predicted to contain SHF progenitors, based on evolutionary conservation of ALPM patterning. Traced cells were identified in SHF-derived distal ventricular myocardium and in three lineages in the outflow tract (OFT). We confirmed the extent of contributions made by ALPM nkx2.5(+) cells using Kaede photoconversion. Taken together, these data demonstrate that, as in higher vertebrates, zebrafish SHF progenitors are specified within the ALPM and express nkx2.5. Furthermore, we tested the hypothesis that Nkx2.5 plays a conserved and essential role during zebrafish SHF development. Embryos injected with an nkx2.5 morpholino exhibited SHF phenotypes caused by compromised progenitor cell proliferation. Co-injecting low doses of nkx2.5 and ltbp3 morpholinos revealed a genetic interaction between these factors. Taken together, our data highlight two conserved features of zebrafish SHF development, reveal a novel genetic relationship between nkx2.5 and ltbp3, and underscore the utility of this model organism for deciphering SHF biology.

Electronic laboratory quality assurance program: A method of enhancing the prosthodontic curriculum and addressing accreditation standards.

STATEMENT OF PROBLEM: An electronic quality assurance (eQA) program was developed to replace a paper-based system and to address standards introduced by the Commission on Dental Accreditation (CODA) and to improve educational outcomes. This eQA program provides feedback to predoctoral dental students on prosthodontic laboratory steps at New York University College of Dentistry. PURPOSE: The purpose of this study was to compare the eQA program of performing laboratory quality assurance with the former paper-based format. MATERIAL AND METHODS: Fourth-year predoctoral dental students (n=334) who experienced both the paper-based and the electronic version of the quality assurance program were surveyed about their experiences. Additionally, data extracted from the eQA program were analyzed to identify areas of weakness in the curriculum. RESULTS: The study findings revealed that 73.8% of the students preferred the eQA program to the paper-based version. The average number of treatments that did not pass quality assurance standards was 119.5 per month. This indicated a 6.34% laboratory failure rate. Further analysis of these data revealed that 62.1% of the errors were related to fixed prosthodontic treatment, 27.9% to partial removable dental prostheses, and 10% to complete removable dental prostheses in the first 18 months of program implementation. CONCLUSIONS: The eQA program was favored by dental students who have experienced both electronic and paper-based versions of the system. Error type analysis can yield the ability to create customized faculty standardization sessions and refine the didactic and clinical teaching of the predoctoral students. This program was also able to link patient care activity with the student's laboratory activities, thus addressing the latest requirements of the CODA regarding the competence of graduates in evaluating laboratory work related to their patient care.

Predicting Neuroblastoma Patient Risk Groups, Outcomes, and Treatment Response Using Machine Learning Methods: A Review.

Neuroblastoma, a paediatric malignancy with high rates of cancer-related morbidity and mortality, is of significant interest to the field of paediatric cancers. High-risk NB tumours are usually metastatic and result in survival rates of less than 50%. Machine learning approaches have been applied to various neuroblastoma patient data to retrieve relevant clinical and biological information and develop predictive models. Given this background, this study will catalogue and summarise the literature that has used machine learning and statistical methods to analyse data such as multi-omics, histological sections, and medical images to make clinical predictions. Furthermore, the question will be turned on its head, and the use of machine learning to accurately stratify NB patients by risk groups and to predict outcomes, including survival and treatment response, will be summarised. Overall, this study aims to catalogue and summarise the important work conducted to date on the subject of expression-based predictor models and machine learning in neuroblastoma for risk stratification and patient outcomes including survival, and treatment response which may assist and direct future diagnostic and therapeutic efforts.

Targeting NRAS via miR-1304-5p or farnesyltransferase inhibition confers sensitivity to ALK inhibitors in ALK-mutant neuroblastoma.

Targeting Anaplastic lymphoma kinase (ALK) is a promising therapeutic strategy for aberrant ALK-expressing malignancies including neuroblastoma, but resistance to ALK tyrosine kinase inhibitors (ALK TKI) is a distinct possibility necessitating drug combination therapeutic approaches. Using high-throughput, genome-wide CRISPR-Cas9 knockout screens, we identify miR-1304-5p loss as a desensitizer to ALK TKIs in aberrant ALK-expressing neuroblastoma; inhibition of miR-1304-5p decreases, while mimics of this miRNA increase the sensitivity of neuroblastoma cells to ALK TKIs. We show that miR-1304-5p targets NRAS, decreasing cell viability via induction of apoptosis. It follows that the farnesyltransferase inhibitor (FTI) lonafarnib in addition to ALK TKIs act synergistically in neuroblastoma, inducing apoptosis in vitro. In particular, on combined treatment of neuroblastoma patient derived xenografts with an FTI and an ALK TKI complete regression of tumour growth is observed although tumours rapidly regrow on cessation of therapy. Overall, our data suggests that combined use of ALK TKIs and FTIs, constitutes a therapeutic approach to treat high risk neuroblastoma although prolonged therapy is likely required to prevent relapse.

A cis-regulatory module upstream of deltaC regulated by Ntla and Tbx16 drives expression in the tailbud, presomitic mesoderm and somites.

Somites form by an iterative process from unsegmented, presomitic mesoderm (PSM). Notch pathway components, such as deltaC (dlc) have been shown to play a role in this process, while the T-box transcription factors Ntla and Tbx16 regulate somite formation upstream of this by controlling supply and movement of cells into the PSM during gastrulation and tailbud outgrowth. In this work, we report that Ntla and Tbx16 play a more explicit role in segmentation by directly regulating dlc expression. In addition we describe a cis-regulatory module (CRM) upstream of dlc that drives expression of a reporter in the tailbud, PSM and somites during somitogenesis. This CRM is bound by both Ntla and Tbx16 at a cluster of T-box binding sites, which are required in combination for activation of the CRM.

Patient satisfaction survey of mandibular two-implant-retained overdentures in a predoctoral program.

STATEMENT OF PROBLEM: In response to the Commission of Dental Accreditation (CODA) mandate of a competency in the "replacement of teeth including fixed, removable and implant" prostheses, a predoctoral implant curriculum was implemented at New York University College of Dentistry. The assessment of the success or failure of a program should include an assessment of patient satisfaction with the treatment received in the predoctoral clinics. PURPOSE: The purpose of this study was to measure patient satisfaction with the mandibular 2-implant-retained overdenture therapy received in the predoctoral program at New York University College of Dentistry. MATERIAL AND METHODS: A telephone survey of patients who received an implant-retained overdenture in the predoctoral clinics at New York University, College of Dentistry (n=101) was conducted. Two of the authors contacted patients for participation in the survey and, using a prepared script, asked about their satisfaction with items such as function, comfort, and esthetics in addition to their overall satisfaction with the treatment they received. Data were analyzed with descriptive statistics. RESULTS: The study revealed that 79% of participants were satisfied with their masticatory ability, 84% were satisfied with the comfort of the prosthesis, and 89% were satisfied with the esthetics of their new prosthesis. Additionally, 85% of participants reported satisfaction with the overall treatment experience, and 90% would recommend that a friend receive the same treatment. CONCLUSIONS: The results of this study support the incorporation of treatment with an implant-retained mandibular overdenture as part of the routine care provided in the predoctoral education program to meet the mandates of CODA.

Metastasis in Neuroblastoma and Its Link to Autophagy.

Neuroblastoma is a paediatric malignancy originating from the neural crest that commonly occurs in the abdomen and adrenal gland, leading to cancer-related deaths in children. Distant metastasis can be encountered at diagnosis in greater than half of these neuroblastoma patients. Autophagy, a self-degradative process, plays a key role in stress-related responses and the survival of cells and has been studied in neuroblastoma. Accordingly, in the early stages of metastasis, autophagy may suppress cancer cell invasion and migration, while its role may be reversed in later stages, and it may facilitate metastasis by enhancing cancer cell survival. To that end, a body of literature has revealed the mechanistic link between autophagy and metastasis in neuroblastoma in multiple steps of the metastatic cascade, including cancer cell invasion and migration, anoikis resistance, cancer cell dormancy, micrometastasis, and metastatic outbreak. This review aims to take a step forward and discuss the significance of multiple molecular players and compounds that may link autophagy to metastasis and map their function to various metastatic steps in neuroblastoma.

Neuroblastoma Interaction with the Tumour Microenvironment and Its Implications for Treatment and Disease Progression.

Neuroblastoma, a paediatric malignancy of the peripheral nervous system, displays a wide range of clinical outcomes, including regression to fatality despite extensive treatment. Neuroblastoma tumours display a complex interplay with their surrounding environment, known as the tumour microenvironment, which may affect disease progression and patient prognosis. This study aimed to dissect the ways in which neuroblastoma biology, treatment, prognosis, progression, and relapse are linked with the extracellular matrix, the dichotomous identities of neuroblastoma, various regulatory proteins and RNA, and extracellular vesicles within the backdrop of the tumour microenvironment. In addition, other aspects, such as immune cell infiltration, therapeutic options including monoclonal antibodies and small molecule inhibitors; and the ways in which these may affect disease progression and immunosuppression within the context of the neuroblastoma tumour microenvironment, are addressed. Such studies may shed light on useful therapeutic targets within the tumour microenvironment that may benefit groups of NB patients. Ultimately, a detailed understanding of these aspects will enable the neuroblastoma scientific community to improve treatment options, patient outcomes, and quality of life.