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BioMed Research International 2024The zoonotic viruses pose significant threats to public health. Nipah virus (NiV) is an emerging virus transmitted from bats to humans. The NiV causes severe...
The zoonotic viruses pose significant threats to public health. Nipah virus (NiV) is an emerging virus transmitted from bats to humans. The NiV causes severe encephalitis and acute respiratory distress syndrome, leading to high mortality rates, with fatality rates ranging from 40% to 75%. The first emergence of the disease was found in Malaysia in 1998-1999 and later in Bangladesh, Cambodia, Timor-Leste, Indonesia, Singapore, Papua New Guinea, Vietnam, Thailand, India, and other South and Southeast Asian nations. Currently, no specific vaccines or antiviral drugs are available. The potential advantages of epitope-based vaccines include their ability to elicit specific immune responses while minimizing potential side effects. The epitopes have been identified from the conserved region of viral proteins obtained from the UniProt database. The selection of conserved epitopes involves analyzing the genetic sequences of various viral strains. The present study identified two B cell epitopes, seven cytotoxic T lymphocyte (CTL) epitopes, and seven helper T lymphocyte (HTL) epitope interactions from the NiV proteomic inventory. The antigenic and physiological properties of retrieved protein were analyzed using online servers ToxinPred, VaxiJen v2.0, and AllerTOP. The final vaccine candidate has a total combined coverage range of 80.53%. The tertiary structure of the constructed vaccine was optimized, and its stability was confirmed with the help of molecular simulation. Molecular docking was performed to check the binding affinity and binding energy of the constructed vaccine with TLR-3 and TLR-5. Codon optimization was performed in the constructed vaccine within the K12 strain, to eliminate the danger of codon bias. However, these findings must require further validation to assess their effectiveness and safety. The development of vaccines and therapeutic approaches for virus infection is an ongoing area of research, and it may take time before effective interventions are available for clinical use.
Topics: Nipah Virus; Humans; Computer Simulation; Henipavirus Infections; Viral Vaccines; Epitopes, B-Lymphocyte; Computational Biology; Epitopes, T-Lymphocyte; Vaccination; Molecular Docking Simulation; Viral Proteins; Animals
PubMed: 38962403
DOI: 10.1155/2024/4066641 -
Archives of Academic Emergency Medicine 2024Sport Concussion Assessment Tool (SCAT) aids the physicians in early management of concussion among suspected athletes and its 6 version was published in 2023 in...
INTRODUCTION
Sport Concussion Assessment Tool (SCAT) aids the physicians in early management of concussion among suspected athletes and its 6 version was published in 2023 in English. This study aimed to describe the translation and validation process of SCAT6 from English to Persian.
METHODS
The Persian translation of SCAT6 and its evaluation has been done in seven stages: initial translation, appraisal of the initial translation, back translation, appraisal of the back-translation, validation (face and content validities), final reconciliation and testing by simulation.
RESULTS
Initial translation, was done by two bilingual translators followed by an initial appraisal, which was made by both translators and one general physician. Back translation was done by two naïve translators who were unfamiliar with SCAT6, followed by its appraisal by initial translators. Face and content validity of the translation were surveyed by medical professionals and athletes and the results of the validation process were provided to the reconciliation committee and this committee made the modifications needed. Finally, the use of Persian SCAT6 was simulated and the mean time needed to complete the Persian SCAT6 was roughly a little more than 10 minutes.
CONCLUSIONS
The present study provides the readers with the translation and cross-cultural adaptation process of SCAT6 from English to Persian. This translated version will be distributed among the Iranian sports community for assessing concussions among athletes.
PubMed: 38962368
DOI: 10.22037/aaem.v12i1.2259 -
Archives of Academic Emergency Medicine 2024Distinguishing between ruptured and non-ruptured acute appendicitis presents a significant challenge. This study aimed to validate the accuracy of RAMA-WeRA Risk Score...
INTRODUCTION
Distinguishing between ruptured and non-ruptured acute appendicitis presents a significant challenge. This study aimed to validate the accuracy of RAMA-WeRA Risk Score in predicting ruptured appendicitis (RA) in emergency department.
METHODS
This study was a multicenter diagnostic accuracy study conducted across six hospitals in Thailand from February 1, 2022, to January 20, 2023. The eligibility criteria included individuals aged >15 years suspected of acute appendicitis, presenting to the ED, and having an available pathology report following appendectomy or intraoperative diagnosis by the surgeon. We assessed the screening performance characteristics of RAMA-WeRA Risk Score, in detecting the ruptured appendicitis (RA) cases.
RESULTS
860 patients met the study criteria. 168 (19.38%) had RA and 692 (80.62%) patients had non-RA. The area under the receiver operating characteristic curve (AuROC) of RAMA-WeRA Risk Score was 75.11% (95% CI: 71.10, 79.11). The RAMA-WeRA Risk Score > 6 points (high-risk group) demonstrated a positive likelihood ratio (LR) of 3.22 in detecting the ruptured cases. The sensitivity and specificity of score in > 6 cutoff point was 43.8% (95%CI: 36.2, 51.6) and 86.4% (95%CI: 83.6, 88.9), respectively.
CONCLUSIONS
The RAMA-WeRA Risk Score can predict rupture in patients presenting with suspected acute appendicitis in the emergency department with total accuracy of 75% for high-risk cases.
PubMed: 38962366
DOI: 10.22037/aaem.v12i1.2237 -
Evolutionary Applications Jul 2024DNA cytosine methylation is an important epigenetic mechanism in genomic DNA. In most land plants, it is absent in the chloroplast DNA. We detected methylation in the...
DNA cytosine methylation is an important epigenetic mechanism in genomic DNA. In most land plants, it is absent in the chloroplast DNA. We detected methylation in the chloroplast DNA of the kelp , a non-model macroalgal species of high ecological and economic importance. Since the functional role of the chloroplast methylome is yet largely unknown, this fundamental research assessed the chloroplast DNA cytosine methylation in wild and laboratory raised kelp from different climatic origins (High-Arctic at 79° N, and temperate at 54° N), and in laboratory samples from these origins raised at different temperatures (5, 10 and 15°C). Results suggest genome-wide differences in methylated sites and methylation level between the origins, while rearing temperature had only weak effects on the chloroplast methylome. Our findings point at the importance of matching conditions to origin in restoration and cultivation processes to be valid even on plastid level.
PubMed: 38962361
DOI: 10.1111/eva.13744 -
Frontiers in Pharmacology 2024Gastric cancer, the fifth most prevalent cancer worldwide, is often diagnosed in advanced stages with limited treatment options. Examining the tumor microenvironment...
Dissecting gastric cancer heterogeneity and exploring therapeutic strategies using bulk and single-cell transcriptomic analysis and experimental validation of tumor microenvironment and metabolic interplay.
Gastric cancer, the fifth most prevalent cancer worldwide, is often diagnosed in advanced stages with limited treatment options. Examining the tumor microenvironment (TME) and its metabolic reprogramming can provide insights for better diagnosis and treatment. This study investigates the link between TME factors and metabolic activity in gastric cancer using bulk and single-cell RNA-sequencing data. We identified two molecular subtypes in gastric cancer by analyzing the distinct expression patterns of 81 prognostic genes related to the TME and metabolism, which exhibited significant protein-level interactions. The high-risk subtype had increased stromal content, fibroblast and M2 macrophage infiltration, elevated glycosaminoglycans/glycosphingolipids biosynthesis, and fat metabolism, along with advanced clinicopathological features. It also exhibited low mutation rates and microsatellite instability, associating it with the mesenchymal phenotype. In contrast, the low-risk group showed higher tumor content and upregulated protein and sugar metabolism. We identified a 15-gene prognostic signature representing these characteristics, including CPVL, KYNU, CD36, and GPX3, strongly correlated with M2 macrophages, validated through single-cell analysis and an internal cohort. Despite resistance to immunotherapy, the high-risk group showed sensitivity to molecular targeted agents directed at IGF-1R (BMS-754807) and the PI3K-mTOR pathways (AZD8186, AZD8055). We experimentally validated these promising drugs for their inhibitory effects on MKN45 and MKN28 gastric cells. This study unveils the intricate interplay between TME and metabolic pathways in gastric cancer, offering potential for enhanced diagnosis, patient stratification, and personalized treatment. Understanding molecular features in each subtype enriches our comprehension of gastric cancer heterogeneity and potential therapeutic targets.
PubMed: 38962317
DOI: 10.3389/fphar.2024.1355269 -
Southern African Journal of HIV Medicine 2024Prevention of HIV vertical transmission programmes (VTPs) in South Africa has decreased paediatric HIV. These programmes require integration in referral hospitals.
BACKGROUND
Prevention of HIV vertical transmission programmes (VTPs) in South Africa has decreased paediatric HIV. These programmes require integration in referral hospitals.
OBJECTIVES
To determine knowledge of and attitudes to the national VTP guidelines in staff from Obstetric and Paediatric disciplines at two referral hospitals.
METHOD
Using a cross-sectional design, a questionnaire to assess knowledge of the guidelines and attitudes (awareness, ease-of-use and non-silo practice, measuring integrated practice) was developed and validated locally. Using standard statistical analyses, data from these questionnaires were used to draw comparisons and determine factors associated with knowledge and attitudes.
RESULTS
Of the 249 participants, 138 (55.4%) were in obstetrics, 125 (50.2%) were nurses, and 168 (67.5%) self-identified as junior staff. Knowledge scores were good, median score (Q1-Q3) was 91.7% (79.1-95.8), and higher in those who had discipline-specific training ( = 0.003). Junior staff ( = 0.002) had higher knowledge levels than senior staff. Most (80%) found the guidelines easy to use and had good awareness, which correlated with knowledge and training. Gaps included understanding of antenatal testing of HIV-negative women and timelines for neonatal HIV testing. Staff scored poorly on integrated practice; the median score (Q1-Q3) was 50% (33.3-58.3), which was inversely correlated with knowledge (= -0.146, = 249, = 0.022).
CONCLUSION
Staff in referral hospitals appear to be practising within silos when implementing VTPs, and this may result in failures to ensure integrated practice. Regularised interdisciplinary and interprofessional training may be important to ensure the integrated implementation of VTPs in referral hospitals.
PubMed: 38962300
DOI: 10.4102/sajhivmed.v25i1.1553 -
Frontiers in Oncology 2024A novel systemic immune-inflammation index (SII), based on the neutrophils, lymphocytes, and platelet counts, is associated with the prognosis of several cancers,...
OBJECTIVE
A novel systemic immune-inflammation index (SII), based on the neutrophils, lymphocytes, and platelet counts, is associated with the prognosis of several cancers, including non-metastatic renal cell carcinoma (RCC). In the present study, we evaluate the prognostic significance of SII in patients with metastatic RCC (mRCC) treated with systemic therapy.
METHOD
Relevant studies were searched comprehensively from Web of Science, PubMed, Embase and the Cochrane Library up to January 2024. The pooled hazard ratio (HR) and 95% confidence interval (CI) were extracted from each study to evaluate the prognostic value of SII in patients with mRCC treated with tyrosine kinase inhibitor (TKI) or immune checkpoint inhibitor (ICI).
RESULTS
A total of 12 studies including 4,238 patients were included in the final analysis. High SII was significantly correlated to poor overall survival (OS, HR = 1.88; 95% CI 1.60-2.21; < 0.001) and progression-free survival (PFS, HR = 1.66; 95% CI 1.39-1.99; < 0.001). Stratified by therapy, high SII was also related to the poor OS (TKI: HR = 1.63, < 0.001; ICI: HR = 2.27, < 0.001) and PFS (TKI: HR = 1.67, < 0.001; ICI: HR = 1.88, = 0.002).
CONCLUSION
In conclusion, high SII could serve as an unfavorable factor in patients with mRCC treated with systemic therapy. Stratified by therapies, the elevated SII was also associated with worse prognosis. Whereas, more prospective and large-scale studies are warranted to validate our findings.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024522831, identifier CRD42024522831.
PubMed: 38962274
DOI: 10.3389/fonc.2024.1404753 -
Frontiers in Oncology 2024Angiogenesis plays a pivotal role in colorectal cancer (CRC), yet its underlying mechanisms demand further exploration. This study aimed to elucidate the significance of...
BACKGROUND
Angiogenesis plays a pivotal role in colorectal cancer (CRC), yet its underlying mechanisms demand further exploration. This study aimed to elucidate the significance of angiogenesis-related genes (ARGs) in CRC through comprehensive multi-omics analysis.
METHODS
CRC patients were categorized according to ARGs expression to form angiogenesis-related clusters (ARCs). We investigated the correlation between ARCs and patient survival, clinical features, consensus molecular subtypes (CMS), cancer stem cell (CSC) index, tumor microenvironment (TME), gene mutations, and response to immunotherapy. Utilizing three machine learning algorithms (LASSO, Xgboost, and Decision Tree), we screen key ARGs associated with ARCs, further validated in independent cohorts. A prognostic signature based on key ARGs was developed and analyzed at the scRNA-seq level. Validation of gene expression in external cohorts, clinical tissues, and blood samples was conducted via RT-PCR assay.
RESULTS
Two distinct ARC subtypes were identified and were significantly associated with patient survival, clinical features, CMS, CSC index, and TME, but not with gene mutations. Four genes (S100A4, COL3A1, TIMP1, and APP) were identified as key ARCs, capable of distinguishing ARC subtypes. The prognostic signature based on these genes effectively stratified patients into high- or low-risk categories. scRNA-seq analysis showed that these genes were predominantly expressed in immune cells rather than in cancer cells. Validation in two external cohorts and through clinical samples confirmed significant expression differences between CRC and controls.
CONCLUSION
This study identified two ARG subtypes in CRC and highlighted four key genes associated with these subtypes, offering new insights into personalized CRC treatment strategies.
PubMed: 38962272
DOI: 10.3389/fonc.2024.1413273 -
Frontiers in Oncology 2024The escape from T cell-mediated immune surveillance is an important cause of death for patients with acute myeloid leukemia (AML). This study aims to identify clonal...
OBJECTIVE
The escape from T cell-mediated immune surveillance is an important cause of death for patients with acute myeloid leukemia (AML). This study aims to identify clonal heterogeneity in leukemia progenitor cells and explore molecular or signaling pathways associated with AML immune escape.
METHODS
Single-cell RNA sequencing (scRNA-seq) was performed to identified AML-related cellular subsets, and intercellular communication was analyzed to investigate molecular mechanisms associated with AML immune escape. Bulk RNA sequencing (RNA-seq) was performed to screen differentially expressed genes (DEGs) related to hematopoietic stem cell progenitors (HSC-Prog) in AML, and critical ore signaling pathways and hub genes were found by Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The mRNA level of the hub gene was verified using quantitative real-time PCR (qRT-PCR) and the protein level of human leukocyte antigen A (HLA-A) using enzyme-linked immuno sorbent assay (ELISA).
RESULTS
scRNA-seq analysis revealed a large heterogeneity of HSC-Prog across samples, and the intercellular communication analysis indicated a strong association between HSC-Prog and CD8-T cells, and HSC-Prog also had an association with HLA-A. Transcriptome analysis identified 1748 DEGs, enrichment analysis results showed that non-classical wnt signaling pathway was associated with AML, and 4 pathway-related genes (RHOA, RYK, CSNK1D, NLK) were obtained. After qRT-PCR and ELISA validation, hub genes and HLA-A were found to be down-regulated in AML and up-regulated after activation of the non-classical Wnt signaling pathway.
CONCLUSION
In this study, clonal heterogeneity of HSC-Prog cells in AML was identified, non-classical wnt signaling pathways associated with AML were identified, and it was verified that HLA-A could be upregulated by activation of non-classical wnt signaling, thereby increasing antigen presentation.
PubMed: 38962268
DOI: 10.3389/fonc.2024.1336106 -
Frontiers in Oncology 2024Our previous studies have demonstrated that Raman spectroscopy could be used for skin cancer detection with good sensitivity and specificity. The objective of this study...
BACKGROUND
Our previous studies have demonstrated that Raman spectroscopy could be used for skin cancer detection with good sensitivity and specificity. The objective of this study is to determine if skin cancer detection can be further improved by combining deep neural networks and Raman spectroscopy.
PATIENTS AND METHODS
Raman spectra of 731 skin lesions were included in this study, containing 340 cancerous and precancerous lesions (melanoma, basal cell carcinoma, squamous cell carcinoma and actinic keratosis) and 391 benign lesions (melanocytic nevus and seborrheic keratosis). One-dimensional convolutional neural networks (1D-CNN) were developed for Raman spectral classification. The stratified samples were divided randomly into training (70%), validation (10%) and test set (20%), and were repeated 56 times using parallel computing. Different data augmentation strategies were implemented for the training dataset, including added random noise, spectral shift, spectral combination and artificially synthesized Raman spectra using one-dimensional generative adversarial networks (1D-GAN). The area under the receiver operating characteristic curve (ROC AUC) was used as a measure of the diagnostic performance. Conventional machine learning approaches, including partial least squares for discriminant analysis (PLS-DA), principal component and linear discriminant analysis (PC-LDA), support vector machine (SVM), and logistic regression (LR) were evaluated for comparison with the same data splitting scheme as the 1D-CNN.
RESULTS
The ROC AUC of the test dataset based on the original training spectra were 0.886±0.022 (1D-CNN), 0.870±0.028 (PLS-DA), 0.875±0.033 (PC-LDA), 0.864±0.027 (SVM), and 0.525±0.045 (LR), which were improved to 0.909±0.021 (1D-CNN), 0.899±0.022 (PLS-DA), 0.895±0.022 (PC-LDA), 0.901±0.020 (SVM), and 0.897±0.021 (LR) respectively after augmentation of the training dataset (p<0.0001, Wilcoxon test). Paired analyses of 1D-CNN with conventional machine learning approaches showed that 1D-CNN had a 1-3% improvement (p<0.001, Wilcoxon test).
CONCLUSIONS
Data augmentation not only improved the performance of both deep neural networks and conventional machine learning techniques by 2-4%, but also improved the performance of the models on spectra with higher noise or spectral shifting. Convolutional neural networks slightly outperformed conventional machine learning approaches for skin cancer detection by Raman spectroscopy.
PubMed: 38962264
DOI: 10.3389/fonc.2024.1320220