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Frontiers in Microbiology 2024The is a family of icosahedral viruses with single-stranded, highly diverse positive-sense RNA genomes. Virions consist of a capsid, without envelope, surrounding a...
The is a family of icosahedral viruses with single-stranded, highly diverse positive-sense RNA genomes. Virions consist of a capsid, without envelope, surrounding a core of RNA genome. A typical genome of picornavirus harbors a well-conserved and highly structured RNA element known as the internal ribosome entry site (IRES), functionally essential for viral replication and protein translation. Based on differences in their structures and mechanisms of action, picornaviral IRESs have been categorized into five types: type I, II, III, IV, and V. Compared with the type IV IRES, the others not only are structurally complicated, but also involve multiple initiation factors for triggering protein translation. The type IV IRES, often referred to as hepatitis C virus (HCV)-like IRES due to its structural resemblance to the HCV IRES, exhibits a simpler and more compact structure than those of the other four. The increasing identification of picornaviruses with the type IV IRES suggests that this IRES type seems to reveal strong retention and adaptation in terms of viral evolution. Here, we systematically reviewed structural features and biological functions of the type IV IRES in picornaviruses. A comprehensive understanding of the roles of type IV IRESs will contribute to elucidating the replication mechanism and pathogenesis of picornaviruses.
PubMed: 38855772
DOI: 10.3389/fmicb.2024.1415698 -
Current Psychiatry Reports Apr 2024Web-based programs to prevent sexual offense perpetration could provide an opportunity that avoids many of the barriers associated with in-person treatment. The aim of... (Review)
Review
PURPOSE OF REVIEW
Web-based programs to prevent sexual offense perpetration could provide an opportunity that avoids many of the barriers associated with in-person treatment. The aim of this systematic review is to give an overview of the literature on web-based initiatives aimed at sexual offense perpetration prevention published during the last 10 years (2013-2023) and to report data on the efficacy as well as issues of the discussed initiatives.
RECENT FINDINGS
We included 18 empirical studies discussing web-based perpetration prevention initiatives, of which six are randomized controlled trials. Among the articles, four cover programs focusing on prevention of sexual reoffending and 14 discuss programs aimed at preventing initial sexual offenses. Evaluations and observations of web-based initiatives aimed at preventing sexual offense perpetration show overall promising results and are well-appreciated. However, evaluation studies are scarce and more randomized controlled trials replicating this effect are warranted.
Topics: Humans; Sex Offenses; Sexual Behavior; Internet
PubMed: 38509408
DOI: 10.1007/s11920-024-01489-1 -
Systematic Reviews Feb 2024Systematic reviews and meta-analyses typically require significant time and effort. Machine learning models have the potential to enhance screening efficiency in these...
Systematic reviews and meta-analyses typically require significant time and effort. Machine learning models have the potential to enhance screening efficiency in these processes. To effectively evaluate such models, fully labeled datasets-detailing all records screened by humans and their labeling decisions-are imperative. This paper presents the creation of a comprehensive dataset for a systematic review of treatments for Borderline Personality Disorder, as reported by Oud et al. (2018) for running a simulation study. The authors adhered to the PRISMA guidelines and published both the search query and the list of included records, but the complete dataset with all labels was not disclosed. We replicated their search and, facing the absence of initial screening data, introduced a Noisy Label Filter (NLF) procedure using active learning to validate noisy labels. Following the NLF application, no further relevant records were found. A simulation study employing the reconstructed dataset demonstrated that active learning could reduce screening time by 82.30% compared to random reading. The paper discusses potential causes for discrepancies, provides recommendations, and introduces a decision tree to assist in reconstructing datasets for the purpose of running simulation studies.
Topics: Humans; Machine Learning; Computer Simulation; Problem-Based Learning
PubMed: 38368379
DOI: 10.1186/s13643-024-02472-w -
BMC Surgery Jan 2024The inflammatory response is thought to be a critical initiator of epigenetic alterations. The neutrophil to lymphocyte ratio (NLR), a biomarker of inflammation, is... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The inflammatory response is thought to be a critical initiator of epigenetic alterations. The neutrophil to lymphocyte ratio (NLR), a biomarker of inflammation, is computed by dividing the number of neutrophils by the number of lymphocytes. The primary goal of this systematic review and meta-analysis was to evaluate the pre-operative NLR of gastrointestinal surgery patients who had an anastomotic leak (AL) in comparison to those who did not AL.
METHODS
We performed a comprehensive search for relevant papers published before May 4, 2022, using PubMed, Scopus, and Web of Science. Standardized mean difference (SMD) with a 95% confidence interval (CI) was pooled in meta-analysis to yield a summary estimate. We utilized the random-effects model to create pooled effects since we discovered a substantial heterogeneity level. For evaluating quality, the Newcastle-Ottawa scale (NOS) was implemented.
RESULTS
The research comprised 12 studies with a total of 2940 individuals who had GI operations, 353 of whom went on to develop AL. We discovered that patients who had GI surgeries and acquired AL had significantly higher NLR levels than those who did not (random-effects model: SMD = 0.75, 95% CI = 0.11-1.38, p = 0.02). Patients with AL showed significantly higher NLR levels than control group in retrospective studies (SMD = 0.93, 95% CI = 0.20-1.66, p=0.01) but not in prospective studies (SMD = - 0.11, 95% CI = - 0.65-0.43, p = 0.69), according to the subgroup analysis based on research design. Subgroup analysis based on ethnicity yielded that white patients with AL exhibited significantly higher NLR values than the control group (SMD = 1.35, 95% CI = 0.01-2.68, p = 0.04) but this result was not applied to East Asian patients (SMD = 0.14, 95% CI = -0.13-0.41, p = 0.29).
CONCLUSION
Our research suggests a potential association between preoperative NLR and postoperative AL. However, it is essential to acknowledge the variability in the findings, with significantly higher NLR levels observed in retrospective studies and among white patients, but not consistently replicated in prospective studies and among East Asian patients. Further investigations with larger and more diverse cohorts are warranted to validate these findings and explore potential factors contributing to the observed discrepancies.
Topics: Humans; Anastomotic Leak; Digestive System Surgical Procedures; Lymphocytes; Neutrophils; Prospective Studies; Retrospective Studies; Inflammation; Biomarkers
PubMed: 38184537
DOI: 10.1186/s12893-023-02292-0 -
Journal of Neurology Apr 2024Parkinsonian disorders, including Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP), and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
Parkinsonian disorders, including Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP), and corticobasal syndrome (CBS), exhibit overlapping early-stage symptoms, complicating definitive diagnosis despite heterogeneous cellular and regional pathophysiology. Additionally, the progression and the eventual conversion of prodromal conditions such as REM behavior disorder (RBD) to PD, MSA, or DLB remain challenging to predict. Extracellular vesicles (EVs) are small, membrane-enclosed structures released by cells, playing a vital role in communicating cell-state-specific messages. Due to their ability to cross the blood-brain barrier into the peripheral circulation, measuring biomarkers in blood-isolated speculative CNS enriched EVs has become a popular diagnostic approach. However, replication and independent validation remain challenging in this field. Here, we aimed to evaluate the diagnostic accuracy of speculative CNS-enriched EVs for parkinsonian disorders.
METHODS
We conducted a PRISMA-guided systematic review and meta-analysis, covering 18 studies with a total of 1695 patients with PD, 253 with MSA, 21 with DLB, 172 with PSP, 152 with CBS, 189 with RBD, and 1288 HCs, employing either hierarchical bivariate models or univariate models based on study size.
RESULTS
Diagnostic accuracy was moderate for differentiating patients with PD from HCs, but revealed high heterogeneity and significant publication bias, suggesting an inflation of the perceived diagnostic effectiveness. The bias observed indicates that studies with non-significant or lower effect sizes were less likely to be published. Although results for differentiating patients with PD from those with MSA or PSP and CBS appeared promising, their validity is limited due to the small number of involved studies coming from the same research group. Despite initial reports, our analyses suggest that using speculative CNS-enriched EV biomarkers may not reliably differentiate patients with MSA from HCs or patients with RBD from HCs, due to their lesser accuracy and substantial variability among the studies, further complicated by substantial publication bias.
CONCLUSION
Our findings underscore the moderate, yet unreliable diagnostic accuracy of biomarkers in speculative CNS-enriched EVs in differentiating parkinsonian disorders, highlighting the presence of substantial heterogeneity and significant publication bias. These observations reinforce the need for larger, more standardized, and unbiased studies to validate the utility of these biomarkers but also call for the development of better biomarkers for parkinsonian disorders.
Topics: Humans; Parkinsonian Disorders; Parkinson Disease; Multiple System Atrophy; Supranuclear Palsy, Progressive; REM Sleep Behavior Disorder; Biomarkers; Extracellular Vesicles; Diagnosis, Differential
PubMed: 38103086
DOI: 10.1007/s00415-023-12093-3 -
Scientific Reports Oct 2023Although exercise guidelines now recommend exercise for patients with MCI, the long-term effects of exercise in patients with MCI has not been reviewed systematically.... (Meta-Analysis)
Meta-Analysis
Although exercise guidelines now recommend exercise for patients with MCI, the long-term effects of exercise in patients with MCI has not been reviewed systematically. The aim was to assess (1) the effectiveness of exercise and physical activity (EXPA) interventions in improving long-term patient-relevant cognitive and non-cognitive outcomes in people with mild cognitive impairment, (2) how well the included trials reported details of the intervention, and (3) the extent to which reported endpoints were in line with patient preferences that were assessed in patient workshops. Following PRISMA guidelines, we performed a systematic review and meta-analysis including randomized controlled trials. A total of ten studies were included after searching in six electronic sources from 1995 onwards. There is a trend that 6 + -month EXPA interventions improve global cognition 12 months after initiation. Evidence on long-term effects of EXPA interventions on non-cognitive health outcomes could not be meaningfully pooled and the individual studies reported mixed results. Workshop participants considered freedom from pain and stress, mood, motivation and self-efficacy to be important, but these outcomes were rarely addressed. Too little information is available on intervention details for EXPA programs to be replicated and confidently recommended for patients with MCI. PROSPERO registration in December, 2021 (CRD42021287166).
Topics: Humans; Cognitive Dysfunction; Cognition; Exercise; Exercise Therapy
PubMed: 37872230
DOI: 10.1038/s41598-023-44771-7 -
Communications Medicine Oct 2023Heterogeneity in type 2 diabetes presentation and progression suggests that precision medicine interventions could improve clinical outcomes. We undertook a systematic...
BACKGROUND
Heterogeneity in type 2 diabetes presentation and progression suggests that precision medicine interventions could improve clinical outcomes. We undertook a systematic review to determine whether strategies to subclassify type 2 diabetes were associated with high quality evidence, reproducible results and improved outcomes for patients.
METHODS
We searched PubMed and Embase for publications that used 'simple subclassification' approaches using simple categorisation of clinical characteristics, or 'complex subclassification' approaches which used machine learning or 'omics approaches in people with established type 2 diabetes. We excluded other diabetes subtypes and those predicting incident type 2 diabetes. We assessed quality, reproducibility and clinical relevance of extracted full-text articles and qualitatively synthesised a summary of subclassification approaches.
RESULTS
Here we show data from 51 studies that demonstrate many simple stratification approaches, but none have been replicated and many are not associated with meaningful clinical outcomes. Complex stratification was reviewed in 62 studies and produced reproducible subtypes of type 2 diabetes that are associated with outcomes. Both approaches require a higher grade of evidence but support the premise that type 2 diabetes can be subclassified into clinically meaningful subtypes.
CONCLUSION
Critical next steps toward clinical implementation are to test whether subtypes exist in more diverse ancestries and whether tailoring interventions to subtypes will improve outcomes.
PubMed: 37798471
DOI: 10.1038/s43856-023-00360-3 -
BMC Health Services Research Sep 2023Enhancing health system effectiveness, efficiency, and appropriateness is a management priority in most world countries. Scholars and practitioners have focused on...
RATIONALE
Enhancing health system effectiveness, efficiency, and appropriateness is a management priority in most world countries. Scholars and practitioners have focused on physician engagement to facilitate such outcomes.
OBJECTIVES
Our research was intended to: 1) unravel the definition of physician engagement; 2) understand the factors that promote or impede it; 3) shed light on the implications of physician engagement on organizational performance, quality, and safety; and 4) discuss the tools to measure physician engagement.
METHOD
A scoping review was undertaken. Items were collected through electronic databases search and snowball technique. The PRISMA extension for Scoping Reviews (PRISMA-ScR) statement and checklist was followed to enhance the study replicability.
RESULTS
The search yielded 16,062 records. After an initial screening, 300 were selected for potential inclusion in this literature review. After removing duplicates and records not meeting the inclusion criteria, full-text analysis of 261 records was performed, yielding a total of 174 records.
DISCUSSION
Agreement on the conceptualization of physician engagement is thin; furthermore, scholars disagree on the techniques and approaches used to assess its implementation and implications. Proposals have been made to overcome the barriers to its adoption, but empirical evidence about implementing physician engagement is still scarce.
CONCLUSIONS
Our scoping review highlights the limitations of the extant literature about physician engagement. Physician engagement is a relatively ill-defined concept: developing an evidence base for its actual implementation is necessitated to provide reliable guidance on how the governance of health care organizations could be improved. Although we did not assess the quality or the robustness of current empirical research, our findings call for further research to: 1) identify potential drivers of physician engagement, 2) develop dependable assessment tools providing health care organizations with guidance on how to foster physician engagement, and 3) evaluate engagement's actual impact on health care organizations' performance.
Topics: Humans; Checklist; Concept Formation; Databases, Factual; Physicians; Delivery of Health Care
PubMed: 37749568
DOI: 10.1186/s12913-023-09935-1 -
Biological Psychiatry Mar 2024Noninvasive brain stimulation (NIBS) treatments have gained considerable attention as potential therapeutic intervention for psychiatric disorders. The identification of... (Review)
Review
Noninvasive brain stimulation (NIBS) treatments have gained considerable attention as potential therapeutic intervention for psychiatric disorders. The identification of reliable biomarkers for predicting clinical response to NIBS has been a major focus of research in recent years. Neuroimaging techniques, such as electroencephalography (EEG) and functional magnetic resonance imaging (MRI), have been used to identify potential biomarkers that could predict response to NIBS. However, identifying clinically actionable brain biomarkers requires robustness. In this systematic review, we aimed to summarize the current state of brain biomarker research for NIBS in depression, focusing only on well-powered studies (N ≥ 88) and/or studies that aimed at independently replicating previous findings, either successfully or unsuccessfully. A total of 220 studies were initially identified, of which 18 MRI studies and 18 EEG studies met the inclusion criteria. All focused on repetitive transcranial magnetic stimulation treatment in depression. After reviewing the included studies, we found the following MRI and EEG biomarkers to be most robust: 1) functional MRI-based functional connectivity between the dorsolateral prefrontal cortex and subgenual anterior cingulate cortex, 2) functional MRI-based network connectivity, 3) task-induced EEG frontal-midline theta, and 4) EEG individual alpha frequency. Future prospective studies should further investigate the clinical actionability of these specific EEG and MRI biomarkers to bring biomarkers closer to clinical reality.
Topics: Humans; Prefrontal Cortex; Depression; Prospective Studies; Brain; Transcranial Magnetic Stimulation; Magnetic Resonance Imaging; Electroencephalography
PubMed: 37734515
DOI: 10.1016/j.biopsych.2023.09.009 -
International Journal of Molecular... Aug 2023PARPi, in combination with ionizing radiation, has demonstrated the ability to enhance cellular radiosensitivity in different tumors. The rationale is that the exposure...
PARPi, in combination with ionizing radiation, has demonstrated the ability to enhance cellular radiosensitivity in different tumors. The rationale is that the exposure to radiation leads to both physical and biochemical damage to DNA, prompting cells to initiate three primary mechanisms for DNA repair. Two double-stranded DNA breaks (DSB) repair pathways: (1) non-homologous end-joining (NHEJ) and (2) homologous recombination (HR); and (3) a single-stranded DNA break (SSB) repair pathway (base excision repair, BER). In this scenario, PARPi can serve as radiosensitizers by leveraging the BER pathway. This mechanism heightens the likelihood of replication forks collapsing, consequently leading to the formation of persistent DSBs. Together, the combination of PARPi and radiotherapy is a potent oncological strategy. This combination has proven its efficacy in different tumors. However, in prostate cancer, there are only preclinical studies to support it and, recently, an ongoing clinical trial. The objective of this paper is to perform a review of the current evidence regarding the use of PARPi and radiotherapy (RT) in PCa and to give future insight on this topic.
Topics: Humans; Male; DNA Repair; Medical Oncology; Poly(ADP-ribose) Polymerase Inhibitors; Prostatic Neoplasms; Radiation Oncology
PubMed: 37629155
DOI: 10.3390/ijms241612978