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Frontiers in Endocrinology 2024Well-differentiated pancreatic neuroendocrine tumors (PNETs) can be non-functional or functional, e.g. insulinoma and glucagonoma. The majority of PNETs are sporadic,... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Well-differentiated pancreatic neuroendocrine tumors (PNETs) can be non-functional or functional, e.g. insulinoma and glucagonoma. The majority of PNETs are sporadic, but PNETs also occur in hereditary syndromes, primarily multiple endocrine neoplasia type 1 (MEN1). The Knudson hypothesis stated a second, somatic hit in as the cause of PNETs of MEN1 syndrome. In the recent years, reports on genetic somatic events in both sporadic and hereditary PNETs have emerged, providing a basis for a more detailed molecular understanding of the pathophysiology. In this systematic review and meta-analysis, we made a collation and statistical analysis of aggregated frequent genetic alterations and potential driver events in human grade G1/G2 PNETs.
METHODS
A systematic search was performed in concordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) reporting guidelines of 2020. A search in Pubmed for published studies using whole exome, whole genome, or targeted gene panel (+400 genes) sequencing of human G1/G2 PNETs was conducted at the 25 of September 2023. Fourteen datasets from published studies were included with data on 221 patients and 225 G1/G2 PNETs, which were divided into sporadic tumors, and hereditary tumors with pre-disposing germline variants, and tumors with unknown germline status. Further, non-functioning and functioning PNETs were distinguished into two groups for pathway evaluation. The collated genetical analyses were conducted using the 'maftools' R-package.
RESULTS
Sporadic PNETs accounted 72.0% (162/225), hereditary PNETs 13.3% (30/225), unknown germline status 14.7% (33/225). The most frequently altered gene was , with somatic variants and copy number variations in overall 42% (95/225); hereditary PNETs (germline variations in , , , , , , and/or ) 57% (16/30); sporadic PNETs 36% (58/162); unknown germline status 64% (21/33). The point mutations/indels were distributed throughout . Overall, (16%, 37/225) and -variants (12%, 27/225) were also abundant with missense mutations clustered in mutational hotspots associated with histone binding, and translocase activity, respectively. mutations occurred more frequently in PNETs with mutations, p<0.05. While functioning PNETs shared few variated genes, non-functioning PNETs had more recurrent variations in genes associated with the Phosphoinositide 3-kinase, Wnt, NOTCH, and Receptor Tyrosine Kinase-Ras signaling onco-pathways.
DISCUSSION
The somatic genetic alterations in G1/G2 PNETs are diverse, but with distinct differences between sporadic vs. hereditary, and functional vs. non-functional PNETs. Increased understanding of the genetic alterations may lead to identification of more drivers and driver hotspots in the tumorigenesis in well-differentiated PNETs, potentially giving a basis for the identification of new drug targets. (Funded by Novo Nordisk Foundation, grant number NNF19OC0057915).
Topics: Humans; Pancreatic Neoplasms; Neuroendocrine Tumors; Sequence Analysis, DNA; Mutation
PubMed: 38868744
DOI: 10.3389/fendo.2024.1351624 -
Translational Psychiatry Jun 2024Excessive and persistent aggressiveness is the most common behavioral problem that leads to psychiatric referrals among children. While half of the variance in childhood...
Excessive and persistent aggressiveness is the most common behavioral problem that leads to psychiatric referrals among children. While half of the variance in childhood aggression is attributed to genetic factors, the biological mechanism and the interplay between genes and environment that results in aggression remains elusive. The purpose of this systematic review is to provide an overview of studies examining the genetics of childhood aggression irrespective of psychiatric diagnosis. PubMed, PsycINFO, and MEDLINE databases were searched using predefined search terms for aggression, genes and the specific age group. From the 652 initially yielded studies, eighty-seven studies were systematically extracted for full-text review and for further quality assessment analyses. Findings show that (i) investigation of candidate genes, especially of MAOA (17 studies), DRD4 (13 studies), and COMT (12 studies) continue to dominate the field, although studies using other research designs and methods including genome-wide association and epigenetic studies are increasing, (ii) the published articles tend to be moderate in sizes, with variable methods of assessing aggressive behavior and inconsistent categorizations of tandem repeat variants, resulting in inconclusive findings of genetic main effects, gene-gene, and gene-environment interactions, (iii) the majority of studies are conducted on European, male-only or male-female mixed, participants. To our knowledge, this is the first study to systematically review the effects of genes on youth aggression. To understand the genetic underpinnings of childhood aggression, more research is required with larger, more diverse sample sets, consistent and reliable assessments and standardized definition of the aggression phenotypes. The search for the biological mechanisms underlying child aggression will also benefit from more varied research methods, including epigenetic studies, transcriptomic studies, gene system and genome-wide studies, longitudinal studies that track changes in risk/ameliorating factors and aggression-related outcomes, and studies examining causal mechanisms.
Topics: Child; Female; Humans; Male; Aggression; Catechol O-Methyltransferase; Gene-Environment Interaction; Genome-Wide Association Study; Monoamine Oxidase; Receptors, Dopamine D4
PubMed: 38862490
DOI: 10.1038/s41398-024-02870-7 -
What is the role of circRNAs in the pathogenesis of cervical cancer? A systematic literature review.Frontiers in Genetics 2024Cervical Cancer (CC) is one of the most prevalent neoplasms among women, considered the leading cause of gynecological death worldwide, and the fourth most common type...
Cervical Cancer (CC) is one of the most prevalent neoplasms among women, considered the leading cause of gynecological death worldwide, and the fourth most common type of cancer. Regional metastasis is closely related to the low effectiveness of treatment, and validating biomarkers can optimize accuracy in diagnosis and prognosis. Among the potential biomarkers associated with disease metastasis are circular RNAs (circRNAs), whose altered expression has been linked to CC progression. In this context, this systematic review aims to compile information on the clinical-pathological significance and describe the biological function of circRNAs. Inclusion and exclusion criteria were used to include relevant literature, followed by analysis. Additionally, we employed the UALCAN tools to search for host genes of circRNAs and expression data, miRTargetLink 2.0 to predict interactions of microRNA target genes and the Cytoscape software to predict possible interactions of microRNA target genes. According to the research, most circRNAs were found to be overexpressed and described as regulators of processes such as invasion, cell proliferation, apoptosis and migration. They were also implicated in clinical significance, including metastasis, TNM staging and microRNA interactions. CircRNAs may participate in critical processes in tumorigenesis; therefore, understanding the underlying molecular mechanisms of gene regulation in CC can contribute to the accuracy of diagnosis, prognosis and therapy.
PubMed: 38859935
DOI: 10.3389/fgene.2024.1287869 -
Photodiagnosis and Photodynamic Therapy Jun 2024This systematic review assessed the effectiveness of photodynamic therapy (PDT) in patients with recurrent oral squamous cell carcinoma (OSCC). (Review)
Review
BACKGROUND
This systematic review assessed the effectiveness of photodynamic therapy (PDT) in patients with recurrent oral squamous cell carcinoma (OSCC).
METHODS
Clinical studies on recurrent OSCC treated with PDT alone were included. Combined treatment strategies were excluded. The search was performed on Medline/Pubmed, Cochrane Library, Embase, Web of Science and ClinicalTrials.gov, manual search, and grey literature.
RESULTS
The eleven included studies were observational. The risk of bias and methodological quality were evaluated using the Newcastle-Ottawa Quality Assessment Scale. The studies reported the use of hematoporphyrin derivative, Photofrin, Foscan and 5-aminolevulinic acid. Data on treatment response and survival was collected. Secondarily, postoperative courses and patient's quality of life/acceptance were reported whenever available. Photofrin and Foscan were the most used photosensitisers, with more complete responses. Lesions responding less favourably were on posterior regions or deep-seated in the tissue.
CONCLUSIONS
Although treatment response differs between treatment protocols, PDT stands as a viable treatment option to be considered, as it can achieve therapeutic results and disease-free, long-lasting periods. Partial treatment responses may be of interest when achieving eligibility for other treatment strategies. Despite this study's limitations, which considered four photosensitisers, Photofrin was the most used but more recent photosensitisers like Foscan have greater chemical stability, tissue penetration, and may be more efficacious on recurrent OSCC.
PubMed: 38857775
DOI: 10.1016/j.pdpdt.2024.104242 -
Legal Medicine (Tokyo, Japan) Jun 2024Suicidal hanging resulting in decapitation is rarely documented. This discussion involves a case of a 35-year-old man found decapitated in his residence's garden. A... (Review)
Review
INTRODUCTION
Suicidal hanging resulting in decapitation is rarely documented. This discussion involves a case of a 35-year-old man found decapitated in his residence's garden. A systematic literature review on hanging-induced decapitation was conducted to comprehensively investigate and compare the case to existing literature. The study aims to identify frequently described post-mortem findings in cases of suicidal hanging leading to decapitation.
CASE REPORT
A 35-year-old man was found decapitated in his garden, with a jute strap and chimney debris nearby. The cervical region was completely severed along the dorsoventral and craniocaudal plane, exposing internal structures. A ligature mark was present, along with Amussat's sign and Simon's bleeding.
METHODS
The systematic review of the literature followed PRISMA standards, analyzing 3622 publications from Google Scholar, PubMed, and Scopus databases up to 2023. Inclusion criteria comprised cases of complete or incomplete decapitation resulting from hanging, available in full-text and written in English.
RESULTS
16 articles on hanging-induced decapitation met the selection criteria; 22 cases were analyzed. Studies, mostly from Europe, showed a mean victim age of 44.3, all male. Fall height ranged from 1 m to 18 m, with various suspension media. Most cases displayed complete decapitation, primarily between cervical vertebrae C1 and C3. Some cases noted collateral findings.
CONCLUSIONS
Complete crime scene investigation and thorough post-mortem examination are crucial for reconstructing events, especially with confounding elements. Precise evidence collection and literature comparison are essential to understand the case and substantiate the forensic pathologist's hypothesis in court.
PubMed: 38838410
DOI: 10.1016/j.legalmed.2024.102464 -
Clinical Microbiology and Infection :... May 2024The optimal empiric antibiotic regimen for non-ventilator-associated hospital-acquired pneumonia (HAP) is uncertain. (Review)
Review
Empiric antibiotic regimens in adults with non-ventilator-associated hospital-acquired pneumonia: a systematic review and network meta-analysis of randomized controlled trials.
BACKGROUND
The optimal empiric antibiotic regimen for non-ventilator-associated hospital-acquired pneumonia (HAP) is uncertain.
OBJECTIVES
To compare the effectiveness and safety of alternative empiric antibiotic regimens in HAP using a network meta-analysis.
DATA SOURCES
Medline, EMBASE, Cochrane CENTRAL, Web of Science, and CINAHL from database inception to July 06, 2023.
STUDY ELIGIBILITY CRITERIA
RCTs.
PARTICIPANTS
Adults with clinical suspicion of HAP.
INTERVENTIONS
Any empiric antibiotic regimen vs. another, placebo, or no treatment.
ASSESSMENT OF RISK OF BIAS
Paired reviewers independently assessed risk of bias using a modified Cochrane tool for assessing risk of bias in randomized trials.
METHODS OF DATA SYNTHESIS
Paired reviewers independently extracted data on trial and patient characteristics, antibiotic regimens, and outcomes of interest. We conducted frequentist random-effects network meta-analyses for treatment failure and all-cause mortality and assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation approach.
RESULTS
Thirty-nine RCTs proved eligible. Thirty RCTs involving 4807 participants found low certainty evidence that piperacillin-tazobactam (RR compared to all cephalosporins: 0.65; 95% CI: 0.42, 1.01) and carbapenems (RR compared to all cephalosporins: 0.77; 95% CI: 0.53, 1.11) might be among the most effective in reducing treatment failure. The findings were robust to the secondary analysis comparing piperacillin-tazobactam vs. antipseudomonal cephalosporins or antipseudomonal carbapenems vs. antipseudomonal cephalosporins. Eleven RCTs involving 2531 participants found low certainty evidence that ceftazidime and linezolid combination may not be convincingly different from cephalosporin alone in reducing all-cause mortality. Evidence on other antibiotic regimens is very uncertain. Data on other patient-important outcomes including adverse events was sparse, and we did not perform network or pairwise meta-analysis.
CONCLUSIONS
For empiric antibiotic therapy of adults with HAP, piperacillin-tazobactam might be among the most effective in reducing treatment failure. Empiric methicillin-resistant Staphylococcus aureus coverage may not exert additional benefit in reducing mortality.
REGISTRATION
PROSPERO (CRD 42022297224).
PubMed: 38823453
DOI: 10.1016/j.cmi.2024.05.017 -
Cellular and Molecular Biology... May 2024This review aimed to comprehensively summarize the role of long non-coding RNA (lncRNA) in gliomas, the most common malignant tumors in the central nervous system, and... (Review)
Review
This review aimed to comprehensively summarize the role of long non-coding RNA (lncRNA) in gliomas, the most common malignant tumors in the central nervous system, and explore their potential clinical applications. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic search using the PubMed database was conducted forty studies met the inclusion and exclusion criteria and were analyzed for type of intervention, the study's design, participants' demographics, and outcomes, including attrition. Gliomas, originating within the central nervous system, account for 40-45% of intracranial tumors. Despite advances in neurosurgical techniques, precise radiotherapy, and chemotherapy, the prognosis for glioma patients remains suboptimal. The review highlights the crucial regulatory role of lncRNA in gliomas. Differential expression of various lncRNAs, such as INHEG, SATB2-AS1, PSMB8-AS1, LINC01018, and SPRY4-IT1, has been observed in gliomas, suggesting their involvement in promoting or inhibiting tumorigenesis. Additionally, lncRNAs play roles in glioma characteristics such as proliferation, invasion, migration, angiogenesis, and the presence of glioma stem cells. The potential clinical applications of lncRNA in gliomas involve their association with tumor grading, diameter, metastasis, and family history. This review emphasizes the importance of understanding the molecular mechanisms involving lncRNA in gliomas. The identification of specific lncRNAs associated with gliomas provides potential molecular markers for diagnosis, differentiation, treatment, and prognosis evaluation. Further research is needed to uncover additional key lncRNAs and their underlying mechanisms, ultimately contributing to the improvement of glioma diagnosis and treatment.
Topics: Humans; Brain Neoplasms; Gene Expression Regulation, Neoplastic; Glioma; Prognosis; RNA, Long Noncoding
PubMed: 38814211
DOI: 10.14715/cmb/2024.70.5.34 -
Clinical Microbiology and Infection :... May 2024Cerebrospinal fluid (CSF) galactomannan is an adjunctive test for central nervous system (CNS) aspergillosis diagnosis with unclear diagnostic test characteristics. (Review)
Review
BACKGROUND
Cerebrospinal fluid (CSF) galactomannan is an adjunctive test for central nervous system (CNS) aspergillosis diagnosis with unclear diagnostic test characteristics.
OBJECTIVES
To evaluate the diagnostic test characteristics of CSF galactomannan in CNS aspergillosis.
METHODS
Systematic review and meta-analysis.
DATA SOURCES
MEDLINE, Embase, Web of Science, and Scopus, from inception to 24 February 2023.
STUDY ELIGIBILITY CRITERIA
Prospective and retrospective studies with 1-group and 2-group designs using any galactomannan assay on CSF to diagnose CNS aspergillosis.
PARTICIPANTS
Adult and/or paediatric patients with CNS aspergillosis.
TEST(S)
Galactomannan testing on CSF specimens.
REFERENCE STANDARD
European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORTC/MSGERC) diagnostic criteria, or equivalent.
ASSESSMENT OF RISK OF BIAS
QUADAS-2 assessment in duplicate.
METHODS OF DATA SYNTHESIS
Bivariate restricted maximum likelihood estimation random-effects meta-analysis, summarized using forest and summary receiver operating characteristic plots; bivariate meta-regression models to investigate heterogeneity; and subgroup and sensitivity analyses to explore subgroup effects and methodologic choices (PROSPERO registration: CRD42022296331; funding: none).
RESULTS
We included eight studies (n = 342 participants). The summary estimates of CSF galactomannan sensitivity and specificity were 69.0% (95% CI, 57.2-78.7%) and 94.4% (95% CI, 82.8-98.3%), respectively. Using meta-regression, galactomannan cut-off (p = 0.38), EORTC/MSGERC criteria version (p = 0.48), or whether the reference standard was defined as both proven and probable or only proven aspergillosis (p = 0.48) did not explain observed heterogeneity. No subgroup effects were demonstrated by analysing the EORTC/MSGERC criteria reference standard used (e.g. 2002 vs. 2008 definitions) or whether paediatric patients were included. Diagnostic sensitivity was improved using a galactomannan cut-off of 1.0, and by excluding high risk of bias and 1-group design studies.
DISCUSSION
CSF galactomannan is a highly specific but insensitive test for use as a component of CNS aspergillosis diagnosis. Few included studies, no prospective studies, and a high risk of bias are study limitations.
PubMed: 38810927
DOI: 10.1016/j.cmi.2024.05.013 -
Frontiers in Oncology 2024Lung cancer is the foremost cause of cancer-related death globally, with non-small cell lung cancer (NSCLC) accounting for 85-90% of cases. Targeted therapy is the most...
Progression-free survival estimation of docetaxel-based second-line treatment for advanced non-small cell lung cancer: a pooled analysis from 18 randomized control trials.
BACKGROUND
Lung cancer is the foremost cause of cancer-related death globally, with non-small cell lung cancer (NSCLC) accounting for 85-90% of cases. Targeted therapy is the most essential therapeutic option for NSCLC, other common treatments include radiation therapy, surgery, chemotherapy, and immunotherapy.
OBJECTIVE
Our study objective was to estimate whether progression-free survival (PFS) is an outcome of NSCLC extracted from 18 randomized control trials (RCTs) with docetaxel as experimental group and antineoplastic agent, kinase inhibitor, and monoclonal antibodies as a control group.
METHODS
We selected relevant studies published between 2011 and 2022 using Google Scholar, PubMed, Scopus, Science Direct, and Cochrane Library. Advanced NSCLC, chemotherapy, RCT, docetaxel, and second-line treatment were the terms included in the search. A total of 9738 patients were evaluated from the 18 identified studies. We used the meta package of R Studio to perform the meta-analysis. Graphical funnel plots were used to evaluate publication bias visually.
RESULTS
Patients who underwent docetaxel-based therapy had a considerably longer PFS than those who got antineoplastic agents, kinase inhibitors, or monoclonal antibodies-based treatment. Patients in the standard treatment arm had a slightly longer PFS than those in the experimental therapy arm in the overall meta-analysis.
CONCLUSION
Docetaxel outperformed monoclonal antibodies, antineoplastic agents, and kinase inhibitors in the second-line therapy of advanced NSCLC since PFS was extensively utilized.
PubMed: 38807763
DOI: 10.3389/fonc.2024.1298786 -
Caspian Journal of Internal Medicine 2024Although genetic mutations in additional sex-combs-like 1 (ASXL1) are prevalent in acute myeloid leukemia (AML), their exact impact on the AML prognosis remains... (Review)
Review
BACKGROUND
Although genetic mutations in additional sex-combs-like 1 (ASXL1) are prevalent in acute myeloid leukemia (AML), their exact impact on the AML prognosis remains uncertain. Hence, the present article was carried out to explore the prognostic importance of ASXL1 mutations in AML.
METHODS
We thoroughly searched electronic scientific databases to find eligible papers. Twenty-seven studies with an overall number of 8,953 participants were selected for the current systematic review. The hazard ratio (HR) and 95% confidence interval (CI) for overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS) were extracted from all studies with multivariate or univariate analysis. Pooled HRs and p-values were also calculated as a part of our work.
RESULTS
The pooled HR for OS in multivariable analysis indicated that ASXL1 significantly diminished survival in AML patients (pooled HR: 1.67; 95% CI: 1.342-2.091).
CONCLUSIONS
ASXL1 mutations may confer a poor prognosis in AML. Hence, they may be regarded as potential prognostic factors. However, more detailed studies with different ASXL1 mutations are suggested to shed light on this issue.
PubMed: 38807730
DOI: 10.22088/cjim.15.2.202