Efficacy and safety of platelet-rich plasma and hyaluronic acid combination therapy for knee osteoarthritis: a systematic review and meta-analysis.

BACKGROUND: This study aimed to evaluate whether a combination of platelet-rich plasma (PRP) and hyaluronic acid (HA) is more effective and safer than injection alone for treating KOA. MATERIALS AND METHODS: MEDLINE (PubMed), the Cochrane Library, EMBASE, and Web of Science databases were systematically searched for articles published until January 2024, and gray literature and bibliographic references were searched. All published randomized controlled trials (RCTs) compared pain, functional outcomes, and adverse events (AEs) associated with PRP + HA therapy vs. PRP or HA treatments. Two independent researchers extracted the pertinent data and evaluated the methodological quality following the PRISMA guidelines. The primary outcomes were pain, functional outcomes, and AEs. A fixed-effects model was used for data analysis in cases with low heterogeneity (P > 0.10 and I2 < 50%). Otherwise, a random effects model was used. RESULTS: Ten RCTs involving 943 patients were included in the analysis. The statistical findings did not differ between the treatment of PRP + HA and PRP alone, while a discernible enhancement in treatment efficacy was observed when compared to HA monotherapy: the visual analog scale scores at 1- (mean difference[MD], -1.00; 95% CI: -1.37 - -0.62; P < .001), 6- (MD, -1.87; 95% CI: -3.46 - -0.28; P = .02), 12-months (MD, -2.07; 95% CI: -3.77 - -0.38; P = .02), and the Western Ontario and McMaster Universities Arthritis Index total scores at 12-months (MD, -8.82; 95% CI: -14.48 - -3.16; P = .002). The incidence of adverse events was notably lower with PRP + HA than with HA alone (OR, 0.37; 95% CI: 0.19 - 0.69; P = .00) or PRP alone (OR, 0.51; 95% CI, 0.30 - 0.87; P = .01). CONCLUSIONS: PRP + HA therapy resulted in more pronounced pain and functional improvement in symptomatic KOA patients than HA treatments, and combination therapy may have higher clinical safety than PRP or HA monotherapy.

Representing core gene expression activity relationships using the latent structure implicit in Bayesian networks.

MOTIVATION: Many types of networks, such as co-expression or ChIP-seq-based gene-regulatory networks, provide useful information for biomedical studies. However, they are often too full of connections and difficult to interpret, forming "indecipherable hairballs." RESULTS: To address this issue, we propose that a Bayesian network can summarize the core relationships between gene expression activities. This network, which we call the LatentDAG, is substantially simpler than conventional co-expression network and ChIP-seq networks (by two orders of magnitude). It provides clearer clusters, without extraneous cross-cluster connections, and clear separators between modules. Moreover, one can find a number of clear examples showing how it bridges the connection between steps in the transcriptional regulatory network and other networks (e.g. RNA-binding protein). In conjunction with a graph neural network, the LatentDAG works better than other biological networks in a variety of tasks, including prediction of gene conservation and clustering genes. AVAILABILITY AND IMPLEMENTATION: Code is available at https://github.com/gersteinlab/LatentDAG.

Clinically Available and Reproducible Prediction Models for IDH and CDKN2A/B Gene Status in Adult-type Diffuse Gliomas.

PURPOSE: Isocitrate dehydrogenase (IDH) and cyclin-dependent kinase inhibitor (CDKN) 2A/B status holds important prognostic value in diffuse gliomas. We aimed to construct prediction models using clinically available and reproducible characteristics for predicting IDH-mutant and CDKN2A/B homozygous deletion in adult-type diffuse glioma patients. MATERIALS AND METHODS: This retrospective, two-center study analysed 272 patients with adult-type diffuse glioma (230 for primary cohort and 42 for external validation cohort). Two radiologists independently assessed the patients' images according to the Visually AcceSAble Rembrandt Images (VASARI) feature set. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to optimise variable selection. Multivariable logistic regression analysis was used to develop the prediction models. Calibration plots, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA) were used to validate the models. Nomograms were developed visually based on the prediction models. RESULTS: The interobserver agreement between the two radiologists for VASARI features was excellent (κ range, 0.813-1). For the IDH-mutant prediction model, the area under the curves (AUCs) was 0.88-0.96 in the internal and external validation sets, For the CDKN2A/B homozygous deletion model, the AUCs were 0.80-0.86 in the internal and external validation sets. The decision curves show that both prediction models had good net benefits. CONCLUSION: The prediction models which basing on VASARI and clinical features provided a reliable and clinically meaningful preoperative prediction for IDH and CDKN2A/B status in diffuse glioma patients. These findings provide a foundation for precise preoperative non-invasive diagnosis and personalised treatment approaches for adult-type diffuse glioma patients.

Superatomic Aromaticity in Cyclic Superatomic Molecules: Ligand-Protected Penta-Icosahedral [M@Au11]5 (M = Au, Pt) Clusters.

Pure or doped gold icosahedra, which can be generally viewed as superatoms, are promising candidates for cluster-assembled structures. As the first large-scale ring-like gold cluster, the report of [Au60Se2(Ph3P)10(SeR)15]+ has arisen much interest, where its Au60 core is composed of five vertex-sharing gold icosahedra in a cyclic way. From electronic characters, this Au60 core is a 40e cyclic penta-superatom network formed by five 8e closed-shell superatoms (S2P6). When more valence electrons are introduced into the penta-superatom network by atomic doping, global delocalized bonds are induced in its bonding framework. In the 42e Au60 core of the [Au60Se2Cl15]- cluster, two extra electrons occupy one delocalized π-bonding orbital formed by super D orbitals of five superatoms, resulting in superatomic π aromaticity. In the 46e [Pt@Au11]5 core of [(Pt@Au11)5Ga2Cl15] cluster, three delocalized super-π bonds are formed, which are organized in the similar way as the aromatic C5H5- molecule. The unveiling of superatomic aromaticity promotes our understanding of the stability of cyclic superatom assemblies and extends the family of superatomic bonding patterns.

Effects of salinity on behavior and reproductive toxicity of BPA in adult marine medaka.

Salinity is an important environmental factor influencing the toxicity of chemicals. Bisphenol A (BPA) is an environmental endocrine disruptor with adverse effects on aquatic organisms, such as fish. However, the influence of salinity on the biotoxicity of BPA and the underlying mechanism are unclear. In this study, we exposed marine medaka (Oryzias melastigma) to BPA at different salinities (0 psµ, 15 psµ, and 30 psµ) for 70days to investigate the toxic effects. At 0 psµ salinity, BPA had an inhibitory effect on the swimming behavior of female medaka. At 15 psµ salinity, exposure to BPA resulted in necrotic cells in the ovaries but not on the spermatozoa. In addition, BPA exposure changed the transcript levels of genes related to the nervous system (gap43, elavl3, gfap, mbpa, and α-tubulin) and the hypothalamic-pituitary-gonadal (HPG) axis (fshr, lhr, star, arα, cyp11a, cyp17a1, cyp19a, and erα); the expression changes differed among salinity levels. These results suggest that salinity influences the adverse effects of BPA on the nervous system and reproductive system of medaka. These results emphasize the importance of considering the impact of environmental factors when carrying out ecological risk assessment of pollutants.

Reproductive toxic effects of chronic exposure to bisphenol A and its analogues in marine medaka (Oryzias melastigma).

As awareness of BPA's health risks has increased, many countries and regions have implemented strict controls on its use. Consequently, bisphenol analogues like BPF and BPAF are being increasingly used as substitutes. However, these compounds are also becoming increasingly prevalent in the environment due to production, use and disposal processes. The oceans act as a repository for various pollutants, and recent studies have revealed the extensive presence of bisphenols (BPs, including BPA, BPF, BPAF, etc.) in the marine environment, posing numerous health hazards to marine wildlife. Nevertheless, the reproductive toxicity of these chemicals on marine fish is not comprehensively comprehended yet. Thus, the histological features of the gonads and the gene expression profiles of HPG (Hypothalamic-Pituitary-Gonadal) axis-related genes in marine medaka (Oryzias melastigma) were studied after exposure to single and combined BPs for 70 days. The effects of each exposure group on spawning, embryo fertilization, and hatching in marine medaka were also assessed. Furthermore, the impacts of each exposure group on the genes related to methylation in the F2 and F3 generations were consistently investigated. BPs exposure was found to cause follicular atresia, irregular oocytes, and empty follicles in the ovary; but no significant lesions in the testis were observed. The expression of several HPG axis genes, including cyp19b, 17ßhsd, 3ßhsd, and fshr, resulted in significant changes compared to the control group. The quantity of eggs laid and fertilization rate decreased in all groups treated with BPs, with the BPAF-treated group showing a notable reduction in the number of eggs laid. Additionally, the hatching rate showed a more significant decline in the BPF-treated group. The analysis of methylated genes in the offspring of bisphenol-treated groups revealed significant changes in the expression of genes including amh, dnmt1, dnmt3ab, mbd2, and mecp2, indicating a potential transgenerational impact of bisphenols on phenotype through epigenetic modifications. Overall, the potential detrimental impact of bisphenol on the reproduction of marine medaka emphasizes the need for caution in considering the use of BPAF and BPF as substitutes.

Less-is-more: selecting transcription factor binding regions informative for motif inference.

Numerous statistical methods have emerged for inferring DNA motifs for transcription factors (TFs) from genomic regions. However, the process of selecting informative regions for motif inference remains understudied. Current approaches select regions with strong ChIP-seq signal for a given TF, assuming that such strong signal primarily results from specific interactions between the TF and its motif. Additionally, these selection approaches do not account for non-target motifs, i.e. motifs of other TFs; they presume the occurrence of these non-target motifs infrequent compared to that of the target motif, and thus assume these have minimal interference with the identification of the target. Leveraging extensive ChIP-seq datasets, we introduced the concept of TF signal 'crowdedness', referred to as C-score, for each genomic region. The C-score helps in highlighting TF signals arising from non-specific interactions. Moreover, by considering the C-score (and adjusting for the length of genomic regions), we can effectively mitigate interference of non-target motifs. Using these tools, we find that in many instances, strong ChIP-seq signal stems mainly from non-specific interactions, and the occurrence of non-target motifs significantly impacts the accurate inference of the target motif. Prioritizing genomic regions with reduced crowdedness and short length markedly improves motif inference. This 'less-is-more' effect suggests that ChIP-seq region selection warrants more attention.

Speckle suppression in holographic phase fringe patterns with different level noises based on FFDNet.

In this paper, an ANLVENet speckle suppression method in holographic phase fringe patterns with different level noises is proposed based on FFDNet, combined with asymmetric pyramid non-local block with a verge extraction module. The experimental results are compared to three network models and several representative algorithms. It is shown that the ANLVENet method not only has better superiority in the speckle suppression with different noise levels, but also preserves more details of the image edge. In addition, another speckle noise model is applied in the phase fringe patterns to prove the stronger generalization of the ANLVENet algorithm. The proposed method is suitable for suppressing the speckle with different levels in a large noise range under complex environmental conditions.

Magnetic resonance imaging with upconversion nanoprobes capable of crossing the blood-cerebrospinal fluid barrier.

The central nervous system (CNS) maintains homeostasis with its surrounding environment by restricting the ingress of large hydrophilic molecules, immune cells, pathogens, and other external harmful substances to the brain. This function relies heavily on the blood-cerebrospinal fluid (B-CSF) and blood-brain barrier (BBB). Although considerable research has examined the structure and function of the BBB, the B-CSF barrier has received little attention. Therapies for disorders associated with the central nervous system have the potential to benefit from targeting the B-CSF barrier to enhance medication penetration into the brain. In this study, we synthesized a nanoprobe ANG-PEG-UCNP capable of crossing the B-CSF barrier with high targeting specificity using a hydrocephalus model for noninvasive magnetic resonance ventriculography to understand the mechanism by which the CSF barrier may be crossed and identify therapeutic targets of CNS diseases. This magnetic resonance nanoprobe ANG-PEG-UCNP holds promising potential as a safe and effective means for accurately defining the ventricular anatomy and correctly locating sites of CSF obstruction.

Binding profiles for 954 Drosophila and C. elegans transcription factors reveal tissue specific regulatory relationships.

A catalog of transcription factor (TF) binding sites in the genome is critical for deciphering regulatory relationships. Here we present the culmination of the modERN (model organism Encyclopedia of Regulatory Networks) consortium that systematically assayed TF binding events in vivo in two major model organisms, Drosophila melanogaster (fly) and Caenorhabditis elegans (worm). We describe key features of these datasets, comprising 604 TFs identifying 3.6M sites in the fly and 350 TFs identifying 0.9 M sites in the worm. Applying a machine learning model to these data identifies sets of TFs with a prominent role in promoting target gene expression in specific cell types. TF binding data are available through the ENCODE Data Coordinating Center and at https://epic.gs.washington.edu/modERNresource, which provides access to processed and summary data, as well as widgets to probe cell type-specific TF-target relationships. These data are a rich resource that should fuel investigations into TF function during development.

Toxic Effects of Bisphenol AF Exposure on the Reproduction and Liver of Female Marine Medaka (Oryzias melastigma).

In recent years, bisphenol AF (BPAF) in aquatic environments has drawn attention to its ecological risks. This study aims to investigate the toxic effects of BPAF (188.33 µg/L) exposure for 30 days on female marine medaka (Oryzias melastigma). On the 10th and 30th day of exposure, the toxicity was evaluated using histological analysis of the liver and ovaries and the transcription levels of genes related to the antioxidant system, immune system, and hypothalamic-pituitary-gonadal (HPG) axis. Findings revealed that (1) BPAF exposure caused vacuolation, karyopyknosis and karyolysis in the liver of marine medaka, and the toxic impact augmented with duration; (2) exposure to BPAF for 10 days facilitated the growth and maturation of primary ova, and this exposure had a comparatively inhibitory effect after 30 days; (3) exposure to BPAF resulted in a biphasic regulation of the transcriptional abundance of genes involved in antioxidant and inflammatory response (e.g., il-8, cat), with an initial up-regulation followed by down-regulation. Additionally, it disrupted the transcriptional pattern of HPG axis-related genes (e.g., 3ßhsd, arα). In conclusion, 188.33 µg/L BPAF can alter the expression levels of functionally related genes, impair the structural integrity of marine organisms, and pose a threat to their overall health.

Fusing Positive and Negative CT Contrast Nanoagent for the Sensitive Detection of Hepatoma.

Positive computed tomography (CT) contrast nanoagent has significant applications in diagnosing tumors. However, the sensitive differentiation between hepatoma and normal liver tissue remains challenging. This challenge arises primarily because both normal liver and hepatoma tissues capture the nanoagent, resulting in similar positive CT contrasts. Here, a strategy for fusing positive and negative CT contrast nanoagent is proposed to detect hepatoma. A nanoagent Hf-MOF@AB@PVP initially generates a positive CT contrast signal of 120.3 HU in the liver. Subsequently, it can specifically respond to the acidic microenvironment of hepatoma to generate H2 , further achieving a negative contrast of -96.0 HU. More importantly, the relative position between the negative and positive signals area is helpful to determine the location of hepatoma and normal liver tissues. The distinct contrast difference of 216.3 HU and relative orientation between normal liver and tumor tissues are meaningful to sensitively distinguish hepatoma from normal liver tissue utilizing CT imaging.

Diagnostic performance of prediction models for extraprostatic extension in prostate cancer: a systematic review and meta-analysis.

PURPOSE: In recent decades, diverse nomograms have been proposed to predict extraprostatic extension (EPE) in prostate cancer (PCa). We aimed to systematically evaluate the accuracy of MRI-inclusive nomograms and traditional clinical nomograms in predicting EPE in PCa. The purpose of this meta-analysis is to provide baseline summative and comparative estimates for future study designs. MATERIALS AND METHODS: The PubMed, Embase, and Cochrane databases were searched up to May 17, 2023, to identify studies on prediction nomograms for EPE of PCa. The risk of bias in studies was assessed by using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). Summary estimates of sensitivity and specificity were obtained with bivariate random-effects model. Heterogeneity was investigated through meta-regression and subgroup analysis. RESULTS: Forty-eight studies with a total of 57 contingency tables and 20,395 patients were included. No significant publication bias was observed for either the MRI-inclusive nomograms or clinical nomograms. For MRI-inclusive nomograms predicting EPE, the pooled AUC of validation cohorts was 0.80 (95% CI: 0.76, 0.83). For traditional clinical nomograms predicting EPE, the pooled AUCs of the Partin table and Memorial Sloan Kettering Cancer Center (MSKCC) nomogram were 0.72 (95% CI: 0.68, 0.76) and 0.79 (95% CI: 0.75, 0.82), respectively. CONCLUSION: Preoperative risk stratification is essential for PCa patients; both MRI-inclusive nomograms and traditional clinical nomograms had moderate diagnostic performance for predicting EPE in PCa. This study provides baseline comparative values for EPE prediction for future studies which is useful for evaluating preoperative risk stratification in PCa patients. CRITICAL RELEVANCE STATEMENT: This meta-analysis firstly evaluated the diagnostic performance of preoperative MRI-inclusive nomograms and clinical nomograms for predicting extraprostatic extension (EPE) in prostate cancer (PCa) (moderate AUCs: 0.72-0.80). We provide baseline estimates for EPE prediction, these findings will be useful in assessing preoperative risk stratification of PCa patients. KEY POINTS: • MRI-inclusive nomograms and traditional clinical nomograms had moderate AUCs (0.72-0.80) for predicting EPE. • MRI combined clinical nomogram may improve diagnostic accuracy of MRI alone for EPE prediction. • MSKCC nomogram had a higher specificity than Partin table for predicting EPE. • This meta-analysis provided baseline and comparative estimates of nomograms for EPE prediction for future studies.

Bilateral anterior congenital radial head dislocation in adults: a case report and literature review.

Objective: Congenital dislocation of the radial head (CRHD) is a rare condition, with bilateral anterior cases being even less common worldwide. Only a few cases had residual pain after adulthood, even when left untreated. Herein, we describe an adult case of bilateral anterior CRHD with significant pain and snapping during motion. The aim of this study was to report the physical and radiological findings, treatment methods, and short-term outcomes of our case and to review adult CRHD cases in the literature. Patient: A 21-year-old male patient presented to our hospital with chief complaints of snapping and exacerbated pain during motion in his left elbow. Diagnoses and interventions: Detailed medical history and physical examination results were recorded. Radiographic examinations were performed on the bilateral elbow, and the diagnosis of bilateral anterior congenital radial head dislocation was confirmed. To relieve the pain and snapping in the left elbow, we performed open reduction and fixation of the radial head with annular ligament reconstruction and ulnar osteotomy. Postoperatively, the elbow rested at 90° flexion with a cast for 16 weeks, and the K-wire was removed on the 10th week; afterward, active functional exercises were performed. Outcomes: The patient was followed-up for 1 year. The pain in his left elbow was relieved with a reduction in the visual analog scale score from 7 to 3. The range of motion of the left elbow was changed from 0° to 135° (preoperative) to -5° to 120° (postoperative) (extension-flexion) without any snapping. However, restrictions in external rotation have not yet been fully resolved. Further physical rehabilitation is required. Conclusion: When managing patients with congenital radial head dislocation, the contralateral elbow should be evaluated to identify potential bilateral cases. Surgical options should be discussed with adult patients only for the strong need for functional improvement, although the outcomes may not be fully satisfactory.

Effects of bisphenols on lipid metabolism and neuro-cardiovascular toxicity in marine medaka larvae.

Bisphenols are environmental endocrine disruptors that have detrimental effects on aquatic organisms. Using marine medaka larvae, this study explored the effects of bisphenol compounds [bisphenol A (BPA), bisphenol S (BPS), bisphenol F (BPF), and bisphenol AF (BPAF)] on the early growth and development of aquatic organisms. Marine medaka larvae were exposed to bisphenol compounds at concentrations of 0.05, 0.5, and 5 µM for 72 h, and changes in heartbeat rate, behavior, hormone levels, and gene expression were determined. Bisphenols were shown to have a toxic effect on the cardiovascular system of larvae and can cause neurotoxicity and endocrine disruption, such as changes to thyroid-related hormones. Functional enrichment showed that bisphenols mainly affect lipid metabolism and cardiac muscle contraction of larvae, which implied that the main toxic effects of bisphenols on marine medaka larvae targeted the liver and heart. This study provides a theoretical foundation for evaluating the toxicological effects of bisphenols on the early development of aquatic organisms.

Toxic effects of bisphenol AF on the embryonic development of marine medaka (Oryzias melastigma).

Bisphenol AF (BPAF), an emerging environmental endocrine disruptor, has been detected in surface waters worldwide and has adverse effects on aquatic organisms. The accumulation of BPAF in oceans and its potential toxic effect on marine organisms are important concerns. In this study, the effects of BPAF (10, 100, 1, and 5 mg/L) on marine medaka (Oryzias melastigma) were evaluated, including effects on the survival rate, heart rate, hatchability, morphology, and gene expression in embryos. The survival rate of marine medaka embryos was significantly lower after treatment with 5 mg/L BPAF than in the solvent control group. Exposure to 1 mg/L and 5 mg/L BPAF significantly reduced hatchability. Low-dose BPAF (10 µg/L) significantly accelerated the heart rate of embryos, while high-dose BPAF (5 mg/L) significantly decreased the heart rate. BPAF exposure also resulted in notochord curvature, pericardial edema, yolk sac cysts, cardiovascular bleeding, and caudal curvature in marine medaka. At the molecular level, BPAF exposure affected the transcript levels of genes involved in the thyroid system (dio1, dio3a, trhr2, tg, and thra), cardiovascular system (gata4, atp2a1, and cacna1da), nervous system (elavl3 and gap43), and antioxidant and inflammatory systems (sod, pparß, and il-8) in embryos. These results indicate that BPAF exposure can alter the expression of functional genes, induce abnormal development, and reduce the hatching and survival rates in marine medaka embryos. Overall, BPAF can adversely affect the survival and development of marine medaka embryos, and BPAF may not be an ideal substitute for BPA.

The EN-TEx resource of multi-tissue personal epigenomes & variant-impact models.

Understanding how genetic variants impact molecular phenotypes is a key goal of functional genomics, currently hindered by reliance on a single haploid reference genome. Here, we present the EN-TEx resource of 1,635 open-access datasets from four donors (∼30 tissues × âˆ¼15 assays). The datasets are mapped to matched, diploid genomes with long-read phasing and structural variants, instantiating a catalog of >1 million allele-specific loci. These loci exhibit coordinated activity along haplotypes and are less conserved than corresponding, non-allele-specific ones. Surprisingly, a deep-learning transformer model can predict the allele-specific activity based only on local nucleotide-sequence context, highlighting the importance of transcription-factor-binding motifs particularly sensitive to variants. Furthermore, combining EN-TEx with existing genome annotations reveals strong associations between allele-specific and GWAS loci. It also enables models for transferring known eQTLs to difficult-to-profile tissues (e.g., from skin to heart). Overall, EN-TEx provides rich data and generalizable models for more accurate personal functional genomics.

A radiogenomics biomarker based on immunological heterogeneity for non-invasive prognosis of renal clear cell carcinoma.

Background: Tumor immunological heterogeneity potentially influences the prognostic disparities among patients with clear cell renal cell carcinoma (ccRCC); however, there is a lack of macroscopic imaging tools that can be used to predict immune-related gene expression in ccRCC. Methods: A novel non-invasive radiogenomics biomarker was constructed for immune-related gene expression in ccRCC. First, 520 ccRCC transcriptomic datasets from The Cancer Genome Atlas (TCGA) were analyzed using a non-negative matrix decomposition (NMF) clustering to identify immune-related molecular subtypes. Immune-related prognostic genes were analyzed through Cox regression and Gene Set Enrichment Analysis (GSEA). We then built a risk model based on an immune-related gene subset to predict prognosis in patients with ccRCC. CT images corresponding to the ccRCC patients in The Cancer Imaging Archive (TCIA) database were used to extract radiomic features. To stratify immune-related gene expression levels, extracted radiogenomics features were identified according to standard consecutive steps. A nomogram was built to combine radiogenomics and clinicopathological information through multivariate logistic regression to further enhance the radiogenomics model. Mann-Whitney U test and ROC curves were used to assess the effectiveness of the radiogenomics marker. Results: NMF methods successfully clustered patients into diverse subtypes according to gene expression levels in the tumor microenvironment (TME). The relative abundance of 10 immune cell populations in each tissue was also analyzed. The immune-related genomic signature (consisting of eight genes) of the tumor was shown to be significantly associated with survival in patients with ccRCC in TCGA database. The immune-related genomic signature was delineated by grouping the signature expression as either low- or high-risk. Using TCIA database, we constructed a radiogenomics biomarker consisting of 11 radiomic features that were optimal predictors of immune-related gene signature expression levels, which demonstrated AUC (area under the ROC curve) values of 0.76 and 0.72 in the training and validation groups, respectively. The nomogram built by combining radiomics and clinical pathological information could further improve the predictive efficacy of the radiogenomics model (AUC = 0.81, 074). Conclusions: The novel prognostic radiogenomics biomarker achieved excellent correlation with the immune-related gene expression status of patients with ccRCC and could successfully stratify the survival status of patients in TCGA database. It is anticipated that this work will assist in selecting precise clinical treatment strategies. This study may also lead to precise theranostics for patients with ccRCC in the future.

Immunological Characteristics of Alternative Splicing Profiles Related to Prognosis in Bladder Cancer.

Several studies have found that pathological imbalance of alterative splicing (AS) events is associated with cancer susceptibility. carcinogenicity. Nevertheless, the relationship between heritable variation in AS events and carcinogenicity has not been extensively explored. Here, we downloaded AS event signatures, transcriptome profiles, and matched clinical information from The Cancer Genome Atlas (TCGA) database, identified the prognostic AS-related events via conducting the univariate Cox regression algorism. Subsequently, the prognostic AS-related events were further reduced by the least absolute shrinkage and selection operator (LASSO) logistic regression model, and employed for constructing the risk model. Single-sample (ssGSEA), ESTIMATE, and the CIBERSORT algorithms were conducted to evaluate tumor microenvironment status. CCK8, cell culture scratch, transwell invasion assays and flow cytometry were conducted to confirm the reliability of the model. We found 2751 prognostic-related AS events, and constructed a risk model with seven prognostic-related AS events. Compared with high-risk score patients, the overall survival rate of the patients with low-risk score was remarkably longer. Besides, we further found that risk score was also closely related to alterations in immune cell infiltration and immunotherapeutic molecules, indicating its potential as an observation of immune infiltration and clinical response to immunotherapy. In addition, the downstream target gene (DYM) could be a promising prognostic factor for bladder cancer. Our investigation provided an indispensable reference for ulteriorly exploring the role of AS events in the tumor microenvironment and immunotherapy efficiency, and rendered personalized prognosis monitoring for bladder cancer.

Multi-Phase CT-Based Radiomics Nomogram for Discrimination Between Pancreatic Serous Cystic Neoplasm From Mucinous Cystic Neoplasm.

PURPOSE: This study aimed to develop and verify a multi-phase (MP) computed tomography (CT)-based radiomics nomogram to differentiate pancreatic serous cystic neoplasms (SCNs) from mucinous cystic neoplasms (MCNs), and to compare the diagnostic efficacy of radiomics models for different phases of CT scans. MATERIALS AND METHODS: A total of 170 patients who underwent surgical resection between January 2011 and December 2018, with pathologically confirmed pancreatic cystic neoplasms (SCN=115, MCN=55) were included in this single-center retrospective study. Radiomics features were extracted from plain scan (PS), arterial phase (AP), and venous phase (VP) CT scans. Algorithms were performed to identify the optimal features to build a radiomics signature (Radscore) for each phase. All features from these three phases were analyzed to develop the MP-Radscore. A combined model comprised the MP-Radscore and imaging features from which a nomogram was developed. The accuracy of the nomogram was evaluated using receiver operating characteristic (ROC) curves, calibration tests, and decision curve analysis. RESULTS: For each scan phase, 1218 features were extracted, and the optimal ones were selected to construct the PS-Radscore (11 features), AP-Radscore (11 features), and VP-Radscore (12 features). The MP-Radscore (14 features) achieved better performance based on ROC curve analysis than any single phase did [area under the curve (AUC), training cohort: MP-Radscore 0.89, PS-Radscore 0.78, AP-Radscore 0.83, VP-Radscore 0.85; validation cohort: MP-Radscore 0.88, PS-Radscore 0.77, AP-Radscore 0.83, VP-Radscore 0.84]. The combination nomogram performance was excellent, surpassing those of all other nomograms in both the training cohort (AUC, 0.91) and validation cohort (AUC, 0.90). The nomogram also performed well in the calibration and decision curve analyses. CONCLUSIONS: Radiomics for arterial and venous single-phase models outperformed the plain scan model. The combination nomogram that incorporated the MP-Radscore, tumor location, and cystic number had the best discriminatory performance and showed excellent accuracy for differentiating SCN from MCN.