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Clinical Lung Cancer Jan 2024With the widespread application of immune checkpoint inhibitor (ICI) combined with radiotherapy (RT) for the treatment of lung cancer, increasing attention has been paid... (Meta-Analysis)
Meta-Analysis
Effect of Sequence of Radiotherapy Combined With Immunotherapy on the Incidence of Pneumonitis in Patients With Lung Cancer: A Systematic Review and Network Meta-Analysis.
BACKGROUND
With the widespread application of immune checkpoint inhibitor (ICI) combined with radiotherapy (RT) for the treatment of lung cancer, increasing attention has been paid to treatment-related pneumonitis. The effect of the treatment sequence on the incidence of pneumonitis remains unclear.
METHODS
We searched databases including PubMed, Embase, and ClinicalTrials.gov, meeting abstracts, and reference lists of relevant review articles for literature published on radio- and immunotherapy in lung cancer. Stata software (version 16.0) was used for meta-analysis. Data on the incidence of any grade and ≥ grade 3 pneumonitis was pooled using the random effects model. Bayesian network meta-analysis was used for arm-based pairwise comparisons. Subgroup analyses were performed to identify the potential influencing factors.
RESULTS
Thirty-eight studies met our inclusion criteria. The network meta-analysis showed no significant difference between the incidence of pneumonitis in concurrent ICI with RT (concurrent arm) and RT followed by ICI (RT-first arm) (odds ratio [OR]: 0.71, 95% confidence interval [CI]: 0.10-4.81). In the meta-analysis of single group rates, RT following ICI (ICI-first arm) exhibited higher incidence of any grade pneumonitis compared with concurrent- and RT-first arms, with 0.321 (95% CI: 0.260-0.386) for programmed cell death protein 1 (PD-1) inhibitors from clinical trials, and 0.480 (95% CI: 0.363-0.598) for PD-1 inhibitors from real-world retrospective data, respectively.
CONCLUSION
No significant difference in the incidence of any grade and grade ≥ 3 pneumonitis was found between RT-first and concurrent arms. The ICI-first arm exhibited a higher incidence of pneumonitis, which needs to be further confirmed by follow-up studies.
Topics: Humans; Bayes Theorem; Immunotherapy; Incidence; Lung Neoplasms; Network Meta-Analysis; Pneumonia; Retrospective Studies
PubMed: 37612176
DOI: 10.1016/j.cllc.2023.08.008 -
Cureus Jul 2023Colorectal cancer (CRC) is a major global health concern, accounting for significant cancer-related morbidity and mortality worldwide. Despite advancements in early... (Review)
Review
Protective Effects of Long-Term Usage of Cyclo-Oxygenase-2 Inhibitors on Colorectal Cancer in Genetically Predisposed Individuals and Their Overall Effect on Prognosis: A Systematic Review.
Colorectal cancer (CRC) is a major global health concern, accounting for significant cancer-related morbidity and mortality worldwide. Despite advancements in early detection and treatment modalities, the prevention of CRC remains a critical goal. Cyclo-oxygenase-2 (COX-2) is an inducible enzyme involved in the production of pro-inflammatory prostaglandins, which play a crucial role in various cellular processes, including inflammation, cell proliferation, apoptosis, and angiogenesis. Elevated COX-2 expression has been consistently observed in colorectal tumors, indicating their role in the pathogenesis of cancer. COX-2 inhibitors, such as celecoxib and rofecoxib, have been studied as potentially effective treatment modalities due to their ability to decrease prostaglandin levels, which are generally higher in cancer patients. Aberrant prostaglandin production is linked to the adenoma-carcinoma sequence, during which adenomas turn dysplastic and accumulate enough damage to become malignant. COX-2 inhibitors have also been shown to modulate various signaling pathways involved in CRC development, such as wingless-related integration site/β-catenin (Wnt/β-catenin), mitogen-activated protein kinase (MAPK), and phosphoinositide-3-kinase-protein kinase B/Akt (PI3K/Akt) pathways. This systematic review aimed to evaluate the protective effects of long-term usage of COX-2 inhibitors on CRC in genetically predisposed individuals and their overall effect on the prognosis of the disease. The researchers conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines and collected data from several databases, including PubMed, PubMed Central, Cochrane Library, and Web of Science. The search strategy combined keywords related to CRC, COX-2 inhibitors, protective effects, and prognosis. They identified 1189 articles and shortlisted 26 full-text articles that met the eligibility criteria. Quality assessment tools, such as the Assessment of Multiple Systematic Review (AMSTAR) for systematic reviews, the Cochrane bias assessment tool for randomized control trials, the scale for the assessment of narrative review articles (SANRA) checklist for narrative reviews, and the Joanna Briggs Institute (JBI) tool for cross-sectional studies and case reports, are used. This review's conclusions will assist in determining the effectiveness of COX-2 inhibitors to prevent CRC. This review may also contribute to developing guidelines for clinicians to manage genetically predisposed individuals with CRC. Furthermore, the results of this review will shed light on the potential of COX-2 inhibitors as a preventive measure against CRC in genetically predisposed individuals.
PubMed: 37588311
DOI: 10.7759/cureus.41939 -
Vaccine Aug 2023Vaccines for avian influenza (AI) can protect poultry against disease, mortality, and virus transmission. Numerous factors, including: vaccine platform, immunogenicity,... (Meta-Analysis)
Meta-Analysis Review
Vaccines for avian influenza (AI) can protect poultry against disease, mortality, and virus transmission. Numerous factors, including: vaccine platform, immunogenicity, and relatedness to the field strain, are known to be important to achieving optimal AI vaccine efficacy. To better understand how these factors contribute to vaccine protection, a systematic meta-analysis was conducted to evaluate efficacy data for vaccines in chickens challenged with highly pathogenic (HP) AI. Data from a total of 120 individual trials from 25 publications were selected and evaluated. Two vaccine criteria were evaluated for their effects on two metrics of protection. The vaccine criteria were: 1) the relatedness of the vaccine antigen and challenge strain in the hemagglutinin 1 domain (HA1) protein sequence; 2) vaccine-induced antibody titers to the challenge virus (VIAC). The metrics of protection were: A) survival of vaccinated chickens vs unvaccinated controls; and B) reduction in oral virus-shedding by vaccinated vs unvaccinated controls 2-4 days post challenge. Three vaccine platforms were evaluated: oil-adjuvanted inactivated whole AI virus, recombinant herpes virus of turkeys (rHVT) vectored, and a non-replicating alpha-virus vectored RNA particle (RP) vaccine. Higher VIAC correlated with greater reduction of virus-shed and vaccine efficacy by all vaccine platforms. Both higher HA1 relatedness and higher VIAC using challenge virus as antigen correlated with better survival by inactivated vaccines and rHVT-vectored vaccines. However, rHVT-vectored and RP based vaccines were more tolerant of variation in the HA1; the relatedness of the HA1 of the vaccine and challenge virus did not significantly correlate with survival with rHVT-vectored vaccines. Protection was achieved with the lowest aa similarity for which there was data, 90-93 % for rHVT vaccines and 88 % for the RP vaccine.
Topics: Animals; Chickens; Influenza Vaccines; Influenza in Birds; Influenza A Virus, H5N1 Subtype; Vaccines, Synthetic; Influenza A virus; Herpesvirus 1, Meleagrid
PubMed: 37537093
DOI: 10.1016/j.vaccine.2023.07.076 -
Expert Review of Anticancer Therapy 2023Studies have shown that myeloma cell leukemia-1 (MCL-1) is associated with the prognosis of patients with cancer. To further validate the prognostic value of MCL-1 in... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Studies have shown that myeloma cell leukemia-1 (MCL-1) is associated with the prognosis of patients with cancer. To further validate the prognostic value of MCL-1 in cancer, a meta-analysis was conducted.
METHODS
Six databases were searched using Boolean logic search formulas. Data were extracted from the included literature, and pooled odds ratio, hazard ratio, and 95% confidence interval were calculated to determine the relationship between MCL-1 levels and clinicopathological characteristics and prognosis of patients with cancer. When heterogeneity was found to be significant, a random effects model was used, otherwise, a fixed effects model was used.
RESULTS
Twelve articles were included in this meta-analysis, totaling 2208 patients with cancer across 14 studies. A high MCL-1 expression level was associated with patients with high T stage, M stage, and TNM stage in some cancers. Additionally, high MCL-1 expression was likely to be observed in patients with poorly differentiated digestive system tumors and patients with lung adenocarcinoma. Notably, a higher expression of MCL-1 was found to be associated with shorter overall survival in patients with hematological tumors, digestive system tumors, and lung cancer.
CONCLUSION
MCL-1 may be a prognostic biomarker in patients with some types of cancer.
Topics: Humans; Biomarkers, Tumor; Digestive System Neoplasms; Leukemia; Myeloid Cell Leukemia Sequence 1 Protein; Myeloid Cells; Prognosis
PubMed: 37467344
DOI: 10.1080/14737140.2023.2238900 -
Briefings in Bioinformatics Jul 2023In only a few years, as a breakthrough technology, clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas) gene-editing systems...
In only a few years, as a breakthrough technology, clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas) gene-editing systems have ushered in the era of genome engineering with a plethora of applications. One of the most promising CRISPR tools, so-called base editors, opened an exciting avenue for exploring new therapeutic approaches through controlled mutagenesis. However, the efficiency of a base editor guide varies depending on several biological determinants, such as chromatin accessibility, DNA repair proteins, transcriptional activity, factors related to local sequence context and so on. Thus, the success of genetic perturbation directed by CRISPR/Cas base-editing systems relies on an optimal single guide RNA (sgRNA) design, taking those determinants into account. Although there is 11 commonly used software to design guides specifically for base editors, only three of them investigated and implemented those biological determinants into their models. This review presents the key features, capabilities and limitations of all currently available software with a particular focus on predictive model-based algorithms. Here, we summarize existing software for sgRNA design and provide a base for improving the efficiency of existing available software suites for precise target base editing.
Topics: RNA, Guide, CRISPR-Cas Systems; Gene Editing; CRISPR-Cas Systems; Software; DNA
PubMed: 37287132
DOI: 10.1093/bib/bbad205 -
Frontiers in Immunology 2023The peptidyl arginine deiminase (PADI) family is a calcium ion-dependent group of isozymes with sequence similarity that catalyze the citrullination of proteins.... (Review)
Review
The peptidyl arginine deiminase (PADI) family is a calcium ion-dependent group of isozymes with sequence similarity that catalyze the citrullination of proteins. Histones can serve as the target substrate of PADI family isozymes, and therefore, the PADI family is involved in NETosis and the secretion of inflammatory cytokines. Thus, the PADI family is associated with the development of inflammatory autoimmune diseases and cancer, reproductive development, and other related diseases. In this review, we systematically discuss the role of the PADI family in the pathogenesis of various diseases based on studies from the past decade to provide a reference for future research.
Topics: Humans; Protein-Arginine Deiminases; Isoenzymes; Autoimmune Diseases; Histones; Neoplasms
PubMed: 37020554
DOI: 10.3389/fimmu.2023.1115794 -
Progress in Biophysics and Molecular... May 2023Biomarker-based tests may facilitate Tuberculosis (TB) diagnosis, accelerate treatment initiation, and thus improve outcomes. This review synthesizes the literature on... (Review)
Review
Biomarker-based tests may facilitate Tuberculosis (TB) diagnosis, accelerate treatment initiation, and thus improve outcomes. This review synthesizes the literature on biomarker-based detection for TB diagnosis using machine learning. The systematic review approach follows the PRISMA guideline. Articles were sought using relevant keywords from Web of Science, PubMed, and Scopus, resulting in 19 eligible studies after a meticulous screening. All the studies were found to have focused on the supervised learning approach, with Support Vector Machine (SVM) and Random Forest emerging as the top two algorithms, with the highest accuracy, sensitivity and specificity reported to be 97.0%, 99.2%, and 98.0%, respectively. Further, protein-based biomarkers were widely explored, followed by gene-based such as RNA sequence and, Spoligotypes. Publicly available datasets were observed to be popularly used by the studies reviewed whilst studies targeting specific cohorts such as HIV patients or children gathering their own data from healthcare facilities, leading to smaller datasets. Of these, most studies used the leave one out cross validation technique to mitigate overfitting. The review shows that machine learning is increasingly assessed in research to improve TB diagnosis through biomarkers, as promising results were shown in terms of model's detection performance. This provides insights on the possible application of machine learning approaches to diagnose TB using biomarkers as opposed to the traditional methods that can be time consuming. Low-middle income settings, where access to basic biomarkers could be provided as compared to sputum-based tests that are not always available, could be a major application of such models.
Topics: Child; Humans; Mycobacterium tuberculosis; HIV Infections; Tuberculosis; Biomarkers; Machine Learning
PubMed: 36931609
DOI: 10.1016/j.pbiomolbio.2023.03.001 -
The Cochrane Database of Systematic... Mar 2023Cystic fibrosis (CF) is a common, life-shortening, genetic disorder in populations of Northern European descent caused by the mutation of a single gene that codes for... (Review)
Review
BACKGROUND
Cystic fibrosis (CF) is a common, life-shortening, genetic disorder in populations of Northern European descent caused by the mutation of a single gene that codes for the production of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. This protein coordinates the transport of salt (and bicarbonate) across cell surfaces, and the mutation most notably affects the airways. In the lungs of people with CF, the defective protein compromises mucociliary clearance and makes the airway prone to chronic infection and inflammation, damaging the structure of the airways and eventually leading to respiratory failure. In addition, abnormalities in the truncated CFTR protein lead to other systemic complications, including malnutrition, diabetes and subfertility. Five classes of mutation have been described, depending on the impact of the mutation on the processing of the CFTR protein in the cell. In class I mutations, premature termination codons prevent the production of any functional protein, resulting in severe CF. Therapies targeting class I mutations aim to enable the normal cellular mechanism to read through the mutation, potentially restoring the production of the CFTR protein. This could, in turn, normalise salt transport in the cells and decrease the chronic infection and inflammation that characterises lung disease in people with CF. This is an update of a previously published review.
OBJECTIVES
To evaluate the benefits and harms of ataluren and similar compounds on clinically important outcomes in people with CF with class I mutations (premature termination codons).
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis Trials Register, which is compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles. The last search of the Cochrane Cystic Fibrosis Trials Register was conducted on 7 March 2022. We searched clinical trial registries maintained by the European Medicines Agency, the US National Institutes of Health and the World Health Organization. The last search of the clinical trials registries was conducted on 4 October 2022.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of parallel design comparing ataluren and similar compounds (specific therapies for class I mutations) with placebo in people with CF who have at least one class I mutation.
DATA COLLECTION AND ANALYSIS
For the included trials, the review authors independently extracted data, assessed the risk of bias and evaluated the certainty of the evidence using GRADE; trial authors were contacted for additional data.
MAIN RESULTS
Our searches identified 56 references to 20 trials; of these, 18 trials were excluded. Both the included parallel RCTs compared ataluren to placebo for 48 weeks in 517 participants (males and females; age range six to 53 years) with CF who had at least one nonsense mutation (a type of class I mutation). The certainty of evidence and risk of bias assessments for the trials were moderate overall. Random sequence generation, allocation concealment and blinding of trial personnel were well documented; participant blinding was less clear. Some participant data were excluded from the analysis in one trial that also had a high risk of bias for selective outcome reporting. PTC Therapeutics Incorporated sponsored both trials with grant support from the Cystic Fibrosis Foundation, the US Food and Drug Administration's Office of Orphan Products Development and the National Institutes of Health. The trials reported no difference between treatment groups in terms of quality of life, and no improvement in respiratory function measures. Ataluren was associated with a higher rate of episodes of renal impairment (risk ratio 12.81, 95% confidence interval 2.46 to 66.65; P = 0.002; I = 0%; 2 trials, 517 participants). The trials reported no treatment effect for ataluren for the review's secondary outcomes of pulmonary exacerbation, computed tomography score, weight, body mass index and sweat chloride. No deaths were reported in the trials. The earlier trial performed a post hoc subgroup analysis of participants not receiving concomitant chronic inhaled tobramycin (n = 146). This analysis demonstrated favourable results for ataluren (n = 72) for the relative change in forced expiratory volume in one second (FEV) per cent (%) predicted and pulmonary exacerbation rate. The later trial aimed to prospectively assess the efficacy of ataluren in participants not concomitantly receiving inhaled aminoglycosides, and found no difference between ataluren and placebo in FEV % predicted and pulmonary exacerbation rate. AUTHORS' CONCLUSIONS: There is currently insufficient evidence to determine the effect of ataluren as a therapy for people with CF with class I mutations. One trial reported favourable results for ataluren in a post hoc subgroup analysis of participants not receiving chronic inhaled aminoglycosides, but these were not reproduced in the later trial, suggesting that the earlier results may have occurred by chance. Future trials should carefully assess for adverse events, notably renal impairment, and consider the possibility of drug interactions. Cross-over trials should be avoided, given the potential for the treatment to change the natural history of CF.
Topics: Adolescent; Adult; Child; Female; Humans; Male; Middle Aged; Young Adult; Aminoglycosides; Anti-Bacterial Agents; Codon, Nonsense; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Mutation; Persistent Infection
PubMed: 36866921
DOI: 10.1002/14651858.CD012040.pub3 -
Genes Jan 2023The ethylene-responsive element binding factor-associated amphiphilic repression (EAR) motif, defined by the consensus sequence patterns LxLxL or DLNx(x)P, is found in a... (Review)
Review
The ethylene-responsive element binding factor-associated amphiphilic repression (EAR) motif, defined by the consensus sequence patterns LxLxL or DLNx(x)P, is found in a diverse range of plant species. It is the most predominant form of active transcriptional repression motif identified so far in plants. Despite its small size (5 to 6 amino acids), the EAR motif is primarily involved in the negative regulation of developmental, physiological and metabolic functions in response to abiotic and biotic stresses. Through an extensive literature review, we identified 119 genes belonging to 23 different plant species that contain an EAR motif and function as negative regulators of gene expression in various biological processes, including plant growth and morphology, metabolism and homeostasis, abiotic stress response, biotic stress response, hormonal pathways and signalling, fertility, and ripening. Positive gene regulation and transcriptional activation are studied extensively, but there remains much more to be discovered about negative gene regulation and the role it plays in plant development, health, and reproduction. This review aims to fill the knowledge gap and provide insights into the role that the EAR motif plays in negative gene regulation, and provoke further research on other protein motifs specific to repressors.
Topics: Arabidopsis; Plants, Genetically Modified; Transcription Factors; Amino Acid Motifs; Transcriptional Activation
PubMed: 36833197
DOI: 10.3390/genes14020270 -
Cell Death & Disease Feb 2023Sepsis is a life-threatening disorder disease defined as infection-induced dysregulated immune responses and multiple organ dysfunction. The imbalance between... (Review)
Review
Sepsis is a life-threatening disorder disease defined as infection-induced dysregulated immune responses and multiple organ dysfunction. The imbalance between hyperinflammation and immunosuppression is a crucial feature of sepsis immunity. Epigenetic modifications, including histone modifications, DNA methylation, chromatin remodeling, and non-coding RNA, play essential roles in regulating sepsis immunity through epi-information independent of the DNA sequence. In recent years, the mechanisms of histone modification in sepsis have received increasing attention, with ongoing discoveries of novel types of histone modifications. Due to the capacity for prolonged effects on immune cells, histone modifications can induce immune cell reprogramming and participate in the long-term immunosuppressed state of sepsis. Herein, we systematically review current mechanisms of histone modifications involved in the regulation of sepsis, summarize their role in sepsis from an immune perspective and provide potential therapeutic opportunities targeting histone modifications in sepsis treatment.
Topics: Humans; Histones; Histone Code; Epigenesis, Genetic; Sepsis; DNA Methylation
PubMed: 36774341
DOI: 10.1038/s41419-023-05656-9