MRI-Based Machine Learning Radiomics for Preoperative Assessment of Human Epidermal Growth Factor Receptor 2 Status in Urothelial Bladder Carcinoma.

BACKGROUND: The human epidermal growth factor receptor 2 (HER2) has recently emerged as hotspot in targeted therapy for urothelial bladder cancer (UBC). The HER2 status is mainly identified by immunohistochemistry (IHC), preoperative and noninvasive methods for determining HER2 status in UBC remain in searching. PURPOSES: To investigate whether radiomics features extracted from MRI using machine learning algorithms can noninvasively evaluate the HER2 status in UBC. STUDY TYPE: Retrospective. POPULATION: One hundred ninety-five patients (age: 68.7 ± 10.5 years) with 14.3% females from January 2019 to May 2023 were divided into training (N = 156) and validation (N = 39) cohorts, and 43 patients (age: 67.1 ± 13.1 years) with 13.9% females from June 2023 to January 2024 constituted the test cohort (N = 43). FIELD STRENGTH/SEQUENCE: 3 T, T2-weighted imaging (turbo spin-echo), diffusion-weighted imaging (breathing-free spin echo). ASSESSMENT: The HER2 status were assessed by IHC. Radiomics features were extracted from MRI images. Pearson correlation coefficient and the least absolute shrinkage and selection operator (LASSO) were applied for feature selection, and six machine learning models were established with optimal features to identify the HER2 status in UBC. STATISTICAL TESTS: Mann-Whitney U-test, chi-square test, LASSO algorithm, receiver operating characteristic analysis, and DeLong test. RESULTS: Three thousand forty-five radiomics features were extracted from each lesion, and 22 features were retained for analysis. The Support Vector Machine model demonstrated the best performance, with an AUC of 0.929 (95% CI: 0.888-0.970) and accuracy of 0.859 in the training cohort, AUC of 0.886 (95% CI: 0.780-0.993) and accuracy of 0.846 in the validation cohort, and AUC of 0.712 (95% CI: 0.535-0.889) and accuracy of 0.744 in the test cohort. DATA CONCLUSION: MRI-based radiomics features combining machine learning algorithm provide a promising approach to assess HER2 status in UBC noninvasively and preoperatively. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

Role of Additional MRI-Based Morphologic Measurements on the Performance of VI-RADS for Muscle-Invasive Bladder Cancer.

BACKGROUND: Vesical Imaging-Reporting and Data System (VI-RADS) is a pathway for the standardized imaging and reporting of bladder cancer staging using multiparametric (mp) MRI. PURPOSE: To investigate additional role of morphological (MOR) measurements to VI-RADS for the detection of muscle-invasive bladder cancer (MIBC) with mpMRI. STUDY TYPE: Retrospective. POPULATION: A total of 198 patients (72 MIBC and 126 NMIBC) underwent bladder mpMRI was included. FIELD STRENGTH/SEQUENCE: 3.0 T/T2-weighted imaging with fast-spin-echo sequence, spin-echo-planar diffusion-weighted imaging and dynamic contrast-enhanced imaging with fast 3D gradient-echo sequence. ASSESSMENT: VI-RADS score and MOR measurement including tumor location, number, stalk, cauliflower-like surface, type of tumor growth, tumor-muscle contact margin (TCM), tumor-longitudinal length (TLL), and tumor cellularity index (TCI) were analyzed by three uroradiologists (3-year, 8-year, and 15-year experience of bladder MRI, respectively) who were blinded to histopathology. STATISTICAL TESTS: Significant MOR measurements associated with MIBC were tested by univariable and multivariable logistic regression (LR) analysis with odds ratio (OR). Area under receiver operating characteristic curve (AUC) with DeLong's test and decision curve analysis (DCA) were used to compared the performance of unadjusted vs. adjusted VI-RADS. A P-value <0.05 was considered statistically significant. RESULTS: TCM (OR 9.98; 95% confidence interval [CI] 4.77-20.8), TCI (OR 5.72; 95% CI 2.37-13.8), and TLL (OR 3.35; 95% CI 1.40-8.03) were independently associated with MIBC at multivariable LR analysis. VI-RADS adjusted by three MORs achieved significantly higher AUC (reader 1 0.908 vs. 0.798; reader 2 0.906 vs. 0.855; reader 3 0.907 vs. 0.831) and better clinical benefits than unadjusted VI-RADS at DCA. Specially in VI-RADS-defined equivocal lesions, MOR-based adjustment resulted in 55.5% (25/45), 70.4% (38/54), and 46.4% (26/56) improvement in accuracy for discriminating MIBC in three readers, respectively. DATA CONCLUSION: MOR measurements improved the performance of VI-RADS in detecting MIBC with mpMRI, especially for equivocal lesions. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Indoxyl sulphate-TNFα axis mediates uremic encephalopathy in rodent acute kidney injury.

Acute kidney injury (AKI) is often accompanied by uremic encephalopathy resulting from accumulation of uremic toxins in brain possibly due to impaired blood-brain barrier (BBB) function. Anionic uremic toxins are substrates or inhibitors of organic anionic transporters (OATs). In this study we investigated the CNS behaviors and expression/function of BBB OAT3 in AKI rats and mice, which received intraperitoneal injection of cisplatin 8 and 20 mg/kg, respectively. We showed that cisplatin treatment significantly inhibited the expressions of OAT3, synaptophysin and microtubule-associated protein 2 (MAP2), impaired locomotor and exploration activities, and increased accumulation of uremic toxins in the brain of AKI rats and mice. In vitro studies showed that uremic toxins neither alter OAT3 expression in human cerebral microvascular endothelial cells, nor synaptophysin and MAP2 expressions in human neuroblastoma (SH-SY5Y) cells. In contrast, tumour necrosis factor alpha (TNFα) and the conditioned medium (CM) from RAW264.7 cells treated with indoxyl sulfate (IS) significantly impaired OAT3 expression. TNFα and CM from IS-treated BV-2 cells also inhibited synaptophysin and MAP2 expressions in SH-SY5Y cells. The alterations caused by TNFα and CMs in vitro, and by AKI and TNFα in vivo were abolished by infliximab, a monoclonal antibody designed to intercept and neutralize TNFα, suggesting that AKI impaired the expressions of OAT3, synaptophysin and MAP2 in the brain via IS-induced TNFα release from macrophages or microglia (termed as IS-TNFα axis). Treatment of mice with TNFα (0.5 mg·kg-1·d-1, i.p. for 3 days) significantly increased p-p65 expression and reduced the expressions of Nrf2 and HO-1. Inhibiting NF-κB pathway, silencing p65, or activating Nrf2 and HO-1 obviously attenuated TNFα-induced downregulation of OAT3, synaptophysin and MAP2 expressions. Significantly increased p-p65 and decreased Nrf2 and HO-1 protein levels were also detected in brain of AKI mice and rats. We conclude that AKI inhibits the expressions of OAT3, synaptophysin and MAP2 due to IS-induced TNFα release from macrophages or microglia. TNFα impairs the expressions of OAT3, synaptophysin and MAP2 partly via activating NF-κB pathway and inhibiting Nrf2-HO-1 pathway.

DEAD-Box Helicase 17 circRNA (circDDX17) Reduces Sorafenib Resistance and Tumorigenesis in Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of liver malignancy. Despite significant progress in HCC treatment, resistance to chemotherapy and tumor metastasis are the main reasons for the unsatisfactory prognosis of HCC. Circular RNAs (circRNAs) have been extensively documented to play a role in the development of various types of cancer. AIMS: Here, we investigated the role of DEAD-box helicase 17 circRNA (circDDX17) in HCC and its underlying molecular mechanisms. METHODS: Our research employed various techniques including reverse transcription-quantitative polymerase chain reaction (RT-qPCR), cell counting kit-8 (CCK-8), flow cytometry, dual luciferase reporter assay, RNA immunoprecipitation (RIP), and western blot analysis. Additionally, we conducted a tumor xenograft assay to investigate the in vivo function of circDDX17. RESULTS: Firstly, the expression of circDDX17 was downregulated in HCC tissues and cells. Through functional experiments, it was observed that the overexpression of circDDX17 enhanced the sensitivity of sorafenib, promoted apoptosis, and inhibited the process of epithelial-mesenchymal transition (EMT) in vitro. Additionally, in vivo studies revealed that circDDX17 reduced tumor growth and increased sorafenib sensitivity. Mechanically, circDDX17 competitively combined miR-21-5p to suppress PTEN expression and activate the PI3K/AKT pathway. Furthermore, our rescue assays demonstrated that circDDX17 act as a tumor suppressor by blocking sorafenib resistance and tumorigenesis, while the inhibitory effect caused by circDDX17 upregulation was neutralized when miR-21-5p was overexpressed, PTEN was silenced, or the PI3K/AKT pathway was activated. CONCLUSION: Our findings firstly confirmed that circDDX17 suppressed sorafenib resistance and HCC progression by regulating miR-21-5p/PTEN/PI3K/AKT pathway, which may provide novel biomarkers for the diagnosis, treatment and prognosis of HCC.

Comprehensive Systematic Review of Poly-L-lactic Acid in Facial Clinical Application.

OBJECTIVES: With the increasing global clinical application of regenerative injection materials, there is a growing recognition of the crucial role played by poly-L-lactic acid (PLLA). The aim of this study is to conduct a systematic review on the therapeutic efficacy and safety of PLLA in clinical applications for facial treatments. METHODS: We conducted a search of the PubMed, EMBASE, Web of Science, and Wanfang databases, followed by screening of the retrieved articles based on predefined inclusion and exclusion criteria. We then performed an analysis on the final set of included articles that met our inclusion criteria. Within these included articles, quality assessment for randomized controlled trials (RCTs) was carried out using the Jadad scale, while non-randomized controlled trials (non-RCTs) were evaluated using the MINORS scale. RESULTS: Our search of above database, using the relevant search terms, yielded a total of 1300 PLLA-related articles. After applying the inclusion and exclusion criteria, 1280 articles were excluded. Only 20 articles, 16 in English and 4 in Chinese, were included in our final analysis, among them 16 NRCTs and 4 RCTs. According to the different clinical evaluation standards, the treatment of PLLA has achieved good outcomes. Most PLLA injection-related adverse events are mild and self-limited, without any additional treatment requirement. CONCLUSION: PLLA is a reasonably safe and effective facial injection material that can be applied in different facial injection areas and depth using various reconstitute and injection methods. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

[Spatiotemporal Evolution and Influencing Factors of Ecosystem Service Value in the Yellow River Basin].

The external spatiotemporal evolution and intrinsic impact mechanisms of ecosystem service value are of great significance for understanding regional ecosystem issues and enhancing human ecological well-being. Based on grid data, this study used the equivalent factor method and NDVI to measure the ecosystem service value of the Yellow River Basin, analyzed the spatial-temporal evolution of urban ecosystem service value along the basin, and established a GWR model to explore the spatial heterogeneity of each influencing factor on the basis of determining the main influencing factors via geographic detector. The results showed that:① The ecosystem service value of the Yellow River Basin increased first, then decreased, and finally increased from 2000 to 2020, showing a spatial distribution pattern of "the south was higher than the north;" "the lower reaches were lower, and the upper and middle reaches were higher;" and the regulation service contributed the most to the ecosystem service value of the basin. ② The results of geographical exploration showed that the degree of influence of various factors was different. Social factors played the strongest role in explaining the ecosystem service value of the Yellow River Basin, followed by economic factors, and natural factors played the weakest role. The high value areas in the upper reaches were mainly related to rivers and lakes, and the high value areas in the middle reaches were mainly related to mountains. ③ The results of the GWR model showed that population density and land reclamation rate were negatively correlated with ecosystem service value, whereas average annual precipitation was positively correlated, and the effects increased from east to west. The GDP per unit area was negatively correlated with the overall ecosystem service value but positively correlated in the upstream region.

Adsorption properties of Pb(II) and Cd(II) in acid mine drainage by oyster shell loaded lignite composite in different morphologies.

A new idea to alleviate environmental pollution is the development of low-cost adsorbents using natural minerals and fishery wastes to treat high concentrations of heavy metal pollutants in acid mine drainage (AMD). Adsorbent morphology, adsorptive and regenerative capacity, and application potential are limiting factors for their large-scale use. Oyster shells capable of releasing alkalinity were loaded on the surface of lignite to develop two composite adsorbents with different morphologies (powdery and globular) for the treatment of AMD containing Pb(II) and Cd(II). The results show that the ability of the adsorbent to treat AMD is closely related to its morphologies. The pseudo-second-order kinetic model and the Langmuir model are suitable to describe the adsorption process of OS-M(P), and the maximum adsorption saturation capacities of Pb(II) and Cd(II) are 332.6219 mg/g and 318.9854 mg/g, respectively. The pseudo-second-order kinetic model and the Freundlich model are suitable to describe the adsorption process of OS-M(G). A synergistic result of electrostatic adsorption, neutralization precipitation, ion exchange and complex reaction is achieved in the removal of Pb(II) and Cd(II) by two morphologies of adsorbents. The regeneration times (5 times) and recovery rate (75.75%) of OS-M(G) are higher than those of OS-M(P) (3 times) and recovery rate (20%). The ability of OS-M(G) to treat actual AMD wastewater is still better than that of OS-M(P). OS-M(G) can be used as a promising environmentally friendly adsorbent for the long-term remediation of AMD. This study provides a comprehensive picture of resource management and reuse opportunities for natural mineral and fishery wastes.

Effect of sheep bone protein hydrolysate on promoting calcium absorption and enhancing bone quality in low-calcium diet fed rats.

Calcium deficiency is prone to fractures, osteoporosis and other symptoms. In this study, sheep bone protein hydrolysates (SBPHs) were obtained by protease hydrolysis. A low-calcium-diet-induced calcium-deficiency rat model was established to investigate the effects of SBPHs on calcium absorption and intestinal flora composition. The results showed that an SBPHs + CaCl2 treatment significantly increased the bone calcium content, bone mineral density, trabecular bone volume, and trabecular thickness, and reduced trabecular separation, and changed the level of bone turnover markers (P < 0.05). Supplementation of SBPHs + CaCl2 can remarkably enhance the bone mechanical strength, and the microstructure of bone was improved, and the trabecular network was more continuous, complete, and thicker. Additionally, SBPHs + CaCl2 dietary increased the abundance of Firmicutes and reduced the abundance of Proteobacteria and Verrucomicrobiota, and promoted the production of short chain fatty acids. This study indicated that SBPHs promoted calcium absorption and could be applied to alleviate osteoporosis.

A novel predict method for muscular invasion of bladder cancer based on 3D mp-MRI feature fusion.

Objective. To assist urologist and radiologist in the preoperative diagnosis of non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC), we proposed a combination models strategy (CMS) utilizing multiparametric magnetic resonance imaging.Approach. The CMS includes three components: image registration, image segmentation, and multisequence feature fusion. To ensure spatial structure consistency of T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and dynamic contrast-enhanced imaging (DCE), a registration network based on patch sampling normalized mutual information was proposed to register DWI and DCE to T2WI. Moreover, to remove redundant information around the bladder, we employed a segmentation network to obtain the bladder and tumor regions from T2WI. Using the coordinate mapping from T2WI, we extracted these regions from DWI and DCE and integrated them into a three-branch dual-channel input. Finally, to fully fuse low-level and high-level features of T2WI, DWI, and DCE, we proposed a distributed multilayer fusion model for preoperative MIBC prediction with five-fold cross-validation.Main results. The study included 436 patients, of which 404 were for the internal cohort and 32 for external cohort. The MIBC was confirmed by pathological examination. In the internal cohort, the area under the curve, accuracy, sensitivity, and specificity achieved by our method were 0.928, 0.869, 0.753, and 0.929, respectively. For the urologist and radiologist, Vesical Imaging-Reporting and Data System score >3 was employed to determine MIBC. The urologist demonstrated an accuracy, sensitivity, and specificity of 0.842, 0.737, and 0.895, respectively, while the radiologist achieved 0.871, 0.803, and 0.906, respectively. In the external cohort, the accuracy of our method was 0.831, which was higher than that of the urologist (0.781) and the radiologist (0.813).Significance. Our proposed method achieved better diagnostic performance than urologist and was comparable to senior radiologist. These results indicate that CMS can effectively assist junior urologists and radiologists in diagnosing preoperative MIBC.

The adsorption of 2-amino-1-methyl-6-phenyl-imidazolium [4, 5-B] pyridine (PhIP) by lactic acid bacteria 37X-15 and its peptidoglycan.

The heterocyclic amine 2-amino-1-methyl-6-phenyl-imidazolium [4, 5-B] pyridine (PhIP), commonly found in roasted meat products, is considered a potential carcinogen. This study is to explore the underlying mechanisms involved in the adsorption of PhIP by lactic acid bacteria 37X-15 and its peptidoglycan. The scanning electron microscope results suggested that the strain's adsorption on PhIP occurs on the cell wall, primarily composed of peptidoglycan. The fourier-transformed infrared spectroscopy results indicated that PhIP adsorption by both lactic acid bacteria 37X-15 and its peptidoglycan primarily involved OH and NH binding groups. Different adsorption conditions affected the adsorption rate of PhIP by peptidoglycan. The optimal values for each adsorption condition were 2 h, 37 °C, and pH 6 when the maximum adsorption rate reached. This study provides a new direction for the application of lactic acid bacteria and its peptidoglycan in food safety.

STAC3 as a poor prognostic biomarker in renal clear cell carcinoma: relationship with immune infiltration.

Calcium ions (Ca2+) are crucial in tumorigenesis and progression, with their elevated levels indicating a negative prognosis in Kidney Renal Clear Cell Carcinoma (KIRC). The influence of genes regulating calcium ions on the survival outcomes of KIRC patients and their interaction with the tumor's immune microenvironment is yet to be fully understood. This study analyzed gene expression data from KIRC tumor and adjacent non-tumor tissues using the TCGA-KIRC dataset to pinpoint genes that are differentially expressed in KIRC. Intersection of these genes with those regulating calcium ions highlighted specific calcium ion-regulating genes that exhibit differential expression in KIRC. Subsequently, prognostic risk models were developed using univariate Cox and LASSO-Cox regression analyses to verify their diagnostic precision. Additionally, the study investigated the correlation between tumor immunity and KIRC patient outcomes, assessing the contribution of STAC3 genes to tumor immunity. Further exploration entailed SSGASE, single-cell analysis, pseudotime analysis and both in vivo and in vitro experiments to evaluate STAC3's role in tumor immunity and progression. Notably, STAC3 was significantly overexpressed in tumor specimens and positively correlated with the degree of malignancy of KIRC, affecting patients' prognosis. Elevated STAC3 expression correlated with enhanced immune infiltration in KIRC tumors. Furthermore, silencing STAC3 curtailed KIRC cell proliferation, migration, invasion, and stemness properties. Experimental models in mice confirmed that STAC3 knockdown led to a reduction in tumor growth. Elevated STAC3 expression is intricately linked with immune infiltration in KIRC tumors, as well as with the aggressive biological behaviors of tumor cells, including their proliferation, migration, and invasion. Targeting STAC3 presents a promising strategy to augment the efficacy of current therapeutic approaches and to better the survival outcomes of patients with KIRC.

[Corrigendum] T7 peptide inhibits angiogenesis via downregulation of angiopoietin­2 and autophagy.

Following the publication of this article, an interested reader drew to the authors' attention that two pairs of protein bands featured in the western blots in Fig. 3A and 5D on p. 679 and 681 respectively appeared to be strikingly similar. After having re­examined their original data, the authors realized that Fig. 5D had been assembled incorrectly. The revised version of Fig. 5, now including the correct data for Fig. 5D, is shown on the next page. Note that the errors made in terms of assembling the data in Fig. 5 did not greatly affect either the results or the conclusions reported in this paper, and all the authors agree to the publication of this corrigendum. The authors regret that these errors went unnoticed prior to the publication of their article, are grateful to the Editor of Oncology Reports for allowing them this opportunity to publish this corrigendum. They also apologize to the readership for any inconvenience caused. [Oncology Reports  33: 675­684, 2015; DOI: 10.3892/or.2014.3653].