Tag: pubmed

Eur Radiol. 2023 Sep 4. doi: 10.1007/s00330-023-10164-7. Online ahead of print.

ABSTRACT

OBJECTIVES: The Image Biomarker Standardization Initiative has helped improve the computational reproducibility of MRI radiomics features. Nonetheless, the MRI sequences and features with high imaging reproducibility are yet to be established. To determine reproducible multiparametric MRI radiomics features across test-retest, multi-scanner, and computational reproducibility comparisons, and to evaluate their clinical value in brain tumor diagnosis.

METHODS: To assess reproducibility, T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and diffusion-weighted imaging (DWI) were acquired from three 3-T MRI scanners using standardized phantom, and radiomics features were extracted using two computational algorithms. Reproducible radiomics features were selected when the concordance correlation coefficient value above 0.9 across multiple sessions, scanners, and computational algorithms. Random forest classifiers were trained with reproducible features (n = 117) and validated in a clinical cohort (n = 50) to evaluate whether features with high reproducibility improved the differentiation of glioblastoma from primary central nervous system lymphomas (PCNSLs).

RESULTS: Radiomics features from T2WI demonstrated higher repeatability (65-94%) than those from DWI (38-48%) or T1WI (2-92%). Across test-retest, multi-scanner, and computational comparisons, T2WI provided 41 reproducible features, DWI provided six, and T1WI provided two. The performance of the classification model with reproducible features was higher than that using non-reproducible features in both training set (AUC, 0.916 vs. 0.877) and validation set (AUC, 0.957 vs. 0.869).

CONCLUSION: Radiomics features with high reproducibility across multiple sessions, scanners, and computational algorithms were identified, and they showed higher diagnostic performance than non-reproducible radiomics features in the differentiation of glioblastoma from PCNSL.

CLINICAL RELEVANCE STATEMENT: By identifying the radiomics features showing higher multi-machine reproducibility, our results also demonstrated higher radiomics diagnostic performance in the differentiation of glioblastoma from PCNSL, paving the way for further research designs and clinical application in neuro-oncology.

KEY POINTS: • Highly reproducible radiomics features across multiple sessions, scanners, and computational algorithms were identified using phantom and applied to clinical diagnosis. • Radiomics features from T2-weighted imaging were more reproducible than those from T1-weighted and diffusion-weighted imaging. • Radiomics features with good reproducibility had better diagnostic performance for brain tumors than features with poor reproducibility.

PMID:37665391 | DOI:10.1007/s00330-023-10164-7

Eur Radiol. 2023 Sep 4. doi: 10.1007/s00330-023-10194-1. Online ahead of print.

ABSTRACT

OBJECTIVES: To explore the potential of dynamic contrast-enhanced MRI (DCE-MRI) quantitative parameters in predicting severe acute radiation-induced rectal injury (RRI) in rectal cancer.

METHODS: This retrospective study enrolled 49 patients with rectal cancer who underwent neoadjuvant chemoradiotherapy and rectal MRI including a DCE-MRI sequence from November 2014 to March 2021. Two radiologists independently measured DCE-MRI quantitative parameters, including the forward volume transfer constant (K^trans), rate constant (k_ep), fractional extravascular extracellular space volume (v_e), and the thickness of the rectal wall farthest away from the tumor. These parameters were compared between mild and severe acute RRI groups based on histopathological assessment. Receiver operating characteristic curve analysis was performed to analyze statistically significant parameters.

RESULTS: Forty-nine patients (mean age, 54 years ± 12 [standard deviation]; 37 men) were enrolled, including 25 patients with severe acute RRI. K^trans was lower in severe acute RRI group than mild acute RRI group (0.032 min^-1 vs 0.054 min^-1; p = 0.008), but difference of other parameters (k_ep, v_e and rectal wall thickness) was not significant between these two groups (all p > 0.05). The area under the receiver operating characteristic curve of K^trans was 0.72 (95% confidence interval: 0.57, 0.84). With a K^trans cutoff value of 0.047 min^-1, the sensitivity and specificity for severe acute RRI prediction were 80% and 54%, respectively.

CONCLUSION: K^trans demonstrated moderate diagnostic performance in predicting severe acute RRI.

CLINICAL RELEVANCE STATEMENT: Dynamic contrast-enhanced MRI can provide non-invasive and objective evidence for perioperative management and treatment strategies in rectal cancer patients with acute radiation-induced rectal injury.

KEY POINTS: • To our knowledge, this study is the first to evaluate the predictive value of contrast-enhanced MRI (DCE-MRI) quantitative parameters for severe acute radiation-induced rectal injury (RRI) in patients with rectal cancer. • Forward volume transfer constant (K^trans), derived from DCE-MRI, exhibited moderate diagnostic performance (AUC = 0.72) in predicting severe acute RRI of rectal cancer, with a sensitivity of 80% and specificity of 54%. • DCE-MRI is a promising imaging marker for distinguishing the severity of acute RRI in patients with rectal cancer.

PMID:37665390 | DOI:10.1007/s00330-023-10194-1

Knee Surg Sports Traumatol Arthrosc. 2023 Sep 4. doi: 10.1007/s00167-023-07555-0. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to evaluate the safety and efficacy of intra-knee stromal vascular fraction (SVF) injection in patients with symptomatic knee osteoarthritis at the midterm (3-year) follow-up.

METHODS: SVF injection was applied to 25 knees of 20 patients. Eighteen patients (90%) were female, and the means ± standard deviations of age was 61.9 ± 7.8 (range, 50-76) years. Patients who received conservative treatment for at least 6 months and had radiographic Kellgren-Lawrence (K-L) grades 2 and 3 varus gonarthrosis were included in the study. SVF was obtained from the umbilical region by liposuction using local anaesthesia. Patients were followed-up for 36 months. Their visual analogue scale (VAS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and Lysholm scores were evaluated before and at 6, 12, 24 and 36 months post-SVF injection.

RESULTS: A statistically significant improvement (p < 0.05) was observed in VAS, WOMAC and Lysholm scores at the first 2-year follow-up compared to baseline. However, no statistically significant difference (n.s.) was observed in VAS, WOMAC and Lysholm scores at the 3-year follow-up compared with baseline.

CONCLUSION: Intra-articular SVF injection decreased pain and significantly improved the functional outcomes in the first 2 years in knees with grade 2-3 osteoarthritis; however, these positive effects of the injection disappeared in the 3rd year. Although short-term successful results of SVF have been reported in the literature, prospective studies are needed for medium- and long-term results.

PMID:37665373 | DOI:10.1007/s00167-023-07555-0

Arch Toxicol. 2023 Sep 4. doi: 10.1007/s00204-023-03572-7. Online ahead of print.

ABSTRACT

Omics techniques have been increasingly recognized as promising tools for Next Generation Risk Assessment. Targeted metabolomics offer the advantage of providing readily interpretable mechanistic information about perturbed biological pathways. In this study, a high-throughput LC-MS/MS-based broad targeted metabolomics system was applied to study nitrofurantoin metabolic dynamics over time and concentration and to provide a mechanistic-anchored approach for point of departure (PoD) derivation. Upon nitrofurantoin exposure at five concentrations (7.5 µM, 15 µM, 20 µM, 30 µM and 120 µM) and four time points (3, 6, 24 and 48 h), the intracellular metabolome of HepG2 cells was evaluated. In total, 256 uniquely identified metabolites were measured, annotated, and allocated in 13 different metabolite classes. Principal component analysis (PCA) and univariate statistical analysis showed clear metabolome-based time and concentration effects. Mechanistic information evidenced the differential activation of cellular pathways indicative of early adaptive and hepatotoxic response. At low concentrations, effects were seen mainly in the energy and lipid metabolism, in the mid concentration range, the activation of the antioxidant cellular response was evidenced by increased levels of glutathione (GSH) and metabolites from the de novo GSH synthesis pathway. At the highest concentrations, the depletion of GSH, together with alternations reflective of mitochondrial impairments, were indicative of a hepatotoxic response. Finally, a metabolomics-based PoD was derived by multivariate PCA using the whole set of measured metabolites. This approach allows using the entire dataset and derive PoD that can be mechanistically anchored to established key events. Our results show the suitability of high throughput targeted metabolomics to investigate mechanisms of hepatoxicity and derive point of departures that can be linked to existing adverse outcome pathways and contribute to the development of new ones.

PMID:37665362 | DOI:10.1007/s00204-023-03572-7

Integr Environ Assess Manag. 2023 Sep 4. doi: 10.1002/ieam.4836. Online ahead of print.

ABSTRACT

Quantifying the effects of environmental stressors on natural resources is problematic due to complex interactions among environmental factors that influence endpoints of interest. This complexity, coupled with data limitations, propagates uncertainty that can make it difficult to causally associate specific environmental stressors with injury endpoints. The Natural Resource Damage Assessment and Restoration (NRDAR) regulations under the Comprehensive Environmental Response, Compensation, and Liability Act and Oil Pollution Act aims to restore natural resources injured by oil spills and hazardous substance releases into the environment; exploration of alternative statistical methods to evaluate effects could be beneficial to addressing NRDAR legal claims. Bayesian networks (BNs) are statistical tools that can be used estimate the influence and interrelatedness of abiotic and biotic environmental variables on environmental endpoints of interest. We investigated the application of a BN for injury assessment using a hypothetical case study by simulating data of acid mine drainage (AMD) affecting a fictional stream-dwelling bird species. We compared the BN-generated probability estimates for injury to a more traditional approach using toxicity thresholds for water and sediment chemistry. BNs offered several distinct advantages compared to traditional approaches, including formalizing the use of expert knowledge, probabilistic estimates of injury using intermediate direct and indirect effects, and the incorporation of a more nuanced and ecologically relevant representation of effects. Given the potential that BNs have for natural resource injury assessment, more research and field-based application is needed to determine their efficacy in NRDAR. We expect the resulting methods will be of interest to many U.S. Federal, State, and Tribal programs devoted to the evaluation, mitigation, remediation, and/or restoration of natural resources injured by releases or spills of contaminants.

PMID:37664978 | DOI:10.1002/ieam.4836

Pediatr Blood Cancer. 2023 Sep 4:e30658. doi: 10.1002/pbc.30658. Online ahead of print.

ABSTRACT

BACKGROUND: Topotecan, an antitumor drug with systemic exposure (SE)-dependent activity against many pediatric tumors has wide interpatient pharmacokinetic variability, making it challenging to attain the desired topotecan SE. The study objectives were to update our topotecan population pharmacokinetic model, to evaluate the feasibility of determining individual topotecan clearance using a single blood sample, and to apply this approach to topotecan data from a neuroblastoma trial to explore exposure-response relationships.

PROCEDURE: Our previous population pharmacokinetic and covariate model was updated using data from 13 clinical pediatric studies. A simulation-based Bayesian analysis was performed to determine if a single blood sample could be sufficient to estimate individual topotecan clearance. Following the Bayesian approach, single pharmacokinetic samples collected from a Children’s Oncology Group Phase III clinical trial (ANBL0532; NCT0056767) were analyzed to estimate individual topotecan SE. Associations between topotecan SE and toxicity or early response were then evaluated.

RESULTS: The updated population model included the impact of patient body surface area (BSA), age, and renal function on topotecan clearance. The Bayesian analysis with the updated model and single plasma samples showed that individual topotecan clearance values were estimated with good precision (mean absolute prediction error ≤16.2%) and low bias (mean prediction error ≤7.2%). Using the same approach, topotecan SE was derived in patients from ANBL0532. The exposure-response analysis showed an increased early response after concomitant cyclophosphamide and topotecan up to a topotecan SE of 45 h ng/mL.

CONCLUSIONS: A simple single-sample approach during topotecan therapy could guide dosing for patients, resulting in more patients reaching target attainment.

PMID:37664968 | DOI:10.1002/pbc.30658

Front Biosci (Landmark Ed). 2023 Aug 23;28(8):175. doi: 10.31083/j.fbl2808175.

ABSTRACT

BACKGROUND: The cause of ulcerative colitis (UC) is not yet fully understood. Previous research has pointed towards a potential role for mutations in nucleotide-binding oligomerization domain-containing protein 2 (NOD2) in promoting the onset and progression of inflammatory bowel disease (IBD) by altering the microbiota of the gut. However, the relationship between toll-like receptor 4 (TLR4) and gut microbiota in IBD is not well understood. To shed light on this, the interaction between TLR4 and gut microbiota was studied using a mouse model of IBD.

METHODS: To examine the function of TLR4 signaling in intestinal injury repair, researchers developed Dextran Sulfate Sodium Salt (DSS)-induced colitis and injury models in both wild-type (WT) mice and TLR4 knockout (TLR4-KO) mice. To assess changes in the gut microbiota, 16S rRNA sequencing was conducted on fecal samples from both the TLR4-KO and WT enteritis mouse models.

RESULTS: The data obtained depicted a protective function of TLR4 against DSS-induced colitis. The gut microbiota composition was found to vary considerably between the WT and TLR4-KO mice groups as indicated by β-diversity analysis and operational taxonomic units (OTUs) cluster. Statistical analysis of microbial multivariate variables depicted an elevated abundance of Escherichia coli/Shigella, Gammaproteobacteria, Tenerlcutes, Deferribacteres, Enterobacteria, Rikenellaceae, and Proteobacteria in the gut microbiota of TLR4-KO mice, whereas there was a considerable reduction in Bacteroidetes at five different levels of the phylogenetic hierarchy including phylum, class, order, family, and genus in comparison with the WT control.

CONCLUSIONS: TLR4 may protect intestinal epithelial cells from damage in response to DSS-induced injury by controlling the microbiota in the gut.

PMID:37664927 | DOI:10.31083/j.fbl2808175

Front Biosci (Landmark Ed). 2023 Aug 31;28(8):189. doi: 10.31083/j.fbl2808189.

ABSTRACT

BACKGROUND: Bladder urothelial carcinoma (BLCA) is a malignancy with a high incidence worldwide. One-third of patients may experience aggressive progression later on, and 70% of patients who have undergone surgical intervention will still suffer from metastasis.

MATERIALS AND METHODS: RNA sequencing profiles of BLCA samples were obtained from The Cancer Genome Atlas (TCGA) database. Differential expression and univariate Cox regression analyses were performed to identify prognosis-related differentially expressed immune genes (DEIGs). Subsequently, a proportional hazards model of DEIGs was then constructed by univariate regression analysis. Differential expression and correlation analyses, CIBERSORT, Single Sample Gene Set Enrichment Analysis (ssGSEA), GSVA were conducted on transcription factors (TFs), immune cells/pathways and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The regulation network was then constructed. Eventually, ATAC-seq, ChIP-seq, scRNA-seq, and multiple online databases were employed for further validation.

RESULTS: A proportional hazards model of 31 DEIGs was constructed and risk score was calculated and proven to be a independent prognostic factor. Then 5 immune genes were characterized to be significantly correlated with bone metastasis, stage and TF expression simultaneously. 4 TFs were identified to be significantly correlated with prognosis and RBP7 expression. 5 immune cells/pathways were revealed to be significantly correlated with RBP7 expression. Only 1 KEGG pathway was identified to be significant in Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) analyses. The regulatory relationship was then constructed, in which the correlation between EBF1 and RBP7 (R = 0.677, p < 0.001), Th2 cells and RBP7 (R = 0.23, p < 0.001), the oocyte meiosis pathway and RBP7 (R = 0.14, p = 0.042) were the most statistically significant. The results were further confirmed by Assay for Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq), Chromatin Immunoprecipitation sequencing (ChIP-seq), single-cell RNA sequencing (scRNA-seq), and multiple online databases validation.

CONCLUSIONS: This study revealed that the EBF1-RBP7 regulatory relationship had potential importance in the bone metastasis in BLCA through Th2 cells and the oocyte meiosis pathway.

PMID:37664915 | DOI:10.31083/j.fbl2808189

Physiother Res Int. 2023 Sep 4:e2048. doi: 10.1002/pri.2048. Online ahead of print.

ABSTRACT

BACKGROUND AND AIM: Nocturnal enuresis (NE) is prevalent in children and adolescents and affects their social life later. Therefore, the objective of this study was to ascertain laser acupuncture (LA) therapy’s effect on NE in adolescent females.

METHODS: Sixty adolescent females diagnosed with chronic monosymptomatic nocturnal enuresis (MNE) were randomly divided into two equal groups: The intervention group (received LA and desmopressin) and the control group (received desmopressin only) (n = 30 each). Treatment was delivered and LA was used three times a week for 12 successive weeks. Abdominal ultrasonography and voiding calendar were used to assess bladder capacity and maximum voiding volume (MVV), respectively. The frequency of bed wetness was assessed throughout the trial period in a diary.

RESULTS: Statistically significant differences were reported in the intervention group. Bladder capacity significantly increased in the intervention group (LA and desmopressin) than in the control group.

CONCLUSIONS: The results of this study suggest the beneficial influences of LA on MNE, despite the very poor quality of the literature’s available evidence.

PMID:37664896 | DOI:10.1002/pri.2048

J Ment Health. 2023 Sep 4:1-29. doi: 10.1080/09638237.2023.2245902. Online ahead of print.

ABSTRACT

BACKGROUND: Substance use amongst young people poses developmental and clinical challenges, necessitating early detection and treatment. Considering the widespread use of technology in young people, delivering interventions digitally may help to reduce and monitor their substance use.

AIMS: We conducted a systematic review and two meta-analyses to assess the effectiveness of digital interventions for reducing substance use (alcohol, smoking, and other substances) among young people aged 10 to 24 years old.

METHOD: Embase, Global Health, Medline, PsychINFO, Web of Science and reference lists of relevant papers were searched in November 2020. Studies were included if they quantitatively evaluated the effectiveness of digital health technologies for treating substance use. A narrative synthesis and meta-analysis were conducted.

RESULTS: Forty-two studies were included in the systematic review and 18 in the meta-analyses. Digital interventions showed small, but statistically significant reductions in weekly alcohol consumption compared to controls (SMD= -0.12, 95% CI= -0.17 to -0.06, I²=0%), but no overall effect was seen on 30-day smoking abstinence (OR = 1.12, 95% CI = 0.70 to 1.80, I²=81%). The effectiveness of digital interventions for reducing substance use is generally weak, however, promising results such as reducing alcohol use were seen. Large-scale studies should investigate the viability of digital interventions, collect user feedback, and determine cost-effectiveness.

PRISMA/PROSPERO: This systematic review was conducted following Cochrane methodology PRISMA guidelines. The review was registered with PROSPERO in November 2020 (CRD42020218442).

PMID:37664884 | DOI:10.1080/09638237.2023.2245902