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.

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.

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.

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.

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.

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.

To mock or not: a comprehensive comparison of mock IP and DNA input for ChIP-seq.

Chromatin immunoprecipitation (IP) followed by sequencing (ChIP-seq) is the gold standard to detect transcription-factor (TF) binding sites in the genome. Its success depends on appropriate controls removing systematic biases. The predominantly used controls, i.e. DNA input, correct for uneven sonication, but not for nonspecific interactions of the IP antibody. Another type of controls, 'mock' IP, corrects for both of the issues, but is not widely used because it is considered susceptible to technical noise. The tradeoff between the two control types has not been investigated systematically. Therefore, we generated comparable DNA input and mock IP experiments. Because mock IPs contain only nonspecific interactions, the sites predicted from them using DNA input indicate the spurious-site abundance. This abundance is highly correlated with the 'genomic activity' (e.g. chromatin openness). In particular, compared to cell lines, complex samples such as whole organisms have more spurious sites-probably because they contain multiple cell types, resulting in more expressed genes and more open chromatin. Consequently, DNA input and mock IP controls performed similarly for cell lines, whereas for complex samples, mock IP substantially reduced the number of spurious sites. However, DNA input is still informative; thus, we developed a simple framework integrating both controls, improving binding site detection.

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.

Supratentorial Extraventricular Ependymomas: Imaging Features and the Added Value of Apparent Diffusion Coefficient.

OBJECTIVE: To improve the understanding and the diagnosis of intracranial ependymal tumors. METHODS: The clinical, radiological and prognostic features of 48 supratentorial extraventricular ependymomas and 74 intraventricular ependymomas were summarized and compared. RESULTS: Supratentorial extraventricular ependymomas, most often located in the frontal lobe (33.3%) and classified as grade III (75.0%), had relatively large eccentric cysts (3.07 ± 2.03 cm), significant enhancement (84.8%), low apparent diffusion coefficient (ADC) values, and associated with higher mortality (41.3%). The majority of intraventricular lesions occurred in the fourth ventricle (86.5%) and classified as grade II (78.4%), had relatively small and multiple cystic changes (1.04 ± 0.87 cm), slight or moderate enhancement (76.9%), high ADC values and associated with lower mortality (20.7%). There were few significant differences between grade II and grade III tumors in these 2 groups, respectively. Young age, high grade and low ADC values are worse prognostic indicators for patients with supratentorial extraventricular ependymomas, but not for those with intraventricular ependymomas. CONCLUSIONS: Conventional radiological features, combined with clinical manifestations and quantitative information provided by diffusion-weighted imaging, may not only enhance the diagnosis and assist in determining prognosis but also provide a better pathophysiological understanding of intracranial ependymal tumors.

6-Arylimino-2-(2-(1-phenylethyl)naphthalen-1-yl)-iminopyridylmetal (Fe and Co) Complexes as Highly Active Precatalysts for Ethylene Polymerization: Influence of Metal and/or Substituents on the Active, Thermostable Performance of Their Complexes and Resultant Polyethylenes.

A series of 6-arylimino-2-(2-(1-phenylethyl)naphthalen-1-yl)iminopyridines and their iron(II) and cobalt(II) complexes (Fe1-Fe5, Co1-Co5) were synthesized and routinely characterized as were Co3 and Co5 complexes, studied by single crystal X-ray crystallography, which individually displayed a distorted square pyramidal or trigonal bipyramid around a cobalt center. Upon treatment with either methyluminoxane (MAO) or modified methyluminoxane (MMAO), all complexes displayed high activities regarding ethylene polymerization even at an elevated temperature, enhancing the thermostability of the active species. In general, iron precatalysts showed higher activities than their cobalt analogs; for example, 10.9 × 106 g(PE) mol-1 (Co) h-1 by Co4 and 17.0 × 106 g(PE) mol-1 (Fe) h-1 by Fe4. Bulkier substituents are favored for increasing the molecular weights of the resultant polyethylenes, such as 25.6 kg mol-1 obtained by Co3 and 297 kg mol-1 obtained by Fe3. A narrow polydispersity of polyethylenes was observed by iron precatalysts activated by MMAO, indicating a single-site active species formed.

HDAC5-mediated deacetylation and nuclear localisation of SOX9 is critical for tamoxifen resistance in breast cancer.

BACKGROUND: Tamoxifen resistance remains a significant clinical challenge for the therapy of ER-positive breast cancer. It has been reported that the upregulation of transcription factor SOX9 in ER+ recurrent cancer is sufficient for tamoxifen resistance. However, the mechanisms underlying the regulation of SOX9 remain largely unknown. METHODS: The acetylation level of SOX9 was detected by immunoprecipitation and western blotting. The expressions of HDACs and SIRTs were evaluated by qRT-PCR. Cell growth was measured by performing MTT assay. ALDH-positive breast cancer stem cells were evaluated by flow cytometry. Interaction between HDAC5 and SOX9 was determined by immunoprecipitation assay. RESULTS: Deacetylation is required for SOX9 nuclear translocation in tamoxifen-resistant breast cancer cells. Furthermore, HDAC5 is the key deacetylase responsible for SOX9 deacetylation and subsequent nuclear translocation. In addition, the transcription factor C-MYC directly promotes the expression of HDAC5 in tamoxifen resistant breast cancer cells. For clinical relevance, high SOX9 and HDAC5 expression are associated with lower survival rates in breast cancer patients treated with tamoxifen. CONCLUSIONS: This study reveals that HDAC5 regulated by C-MYC is essential for SOX9 deacetylation and nuclear localisation, which is critical for tamoxifen resistance. These results indicate a potential therapy strategy for ER+ breast cancer by targeting C-MYC/HDAC5/SOX9 axis.

Benzoquinone induces ROS-dependent mitochondria-mediated apoptosis in HL-60 cells.

Benzene exposure affects the hematopoietic system and leads to the occurrence of various types of leukemia and hematotoxicity. It has been confirmed that active metabolites of benzene, including 1,4-benzoquinone (1,4-BQ), can induce reactive oxygen species (ROS) and apoptosis in the bone marrow, and recent studies have also suggested that benzene exposure can affect mitochondrial function in both experimental animals and cell lines. However, the potential relationship among ROS production, mitochondrial damages, and subsequent apoptosis following benzene exposure has not been well studied in detail. In the present study, we utilized HL-60 cells, a well-characterized human myeloid cell line, as an in vitro model and examined the effects of 1,4-BQ on intracellular ROS formation, mitochondria damage, and the occurrence of apoptotic events with or without using the ROS scavenger N-acetyl-l-cysteine (NAC). The results demonstrated that 1,4-BQ could dose-dependently induce production of ROS and mitochondrial damage as characterized by mitochondrial membrane potential disruption, mitochondrial ultrastructure alteration, and induced apoptosis and activated caspase-3 and caspase-9. Preincubation of HL-60 cells with NAC prior to 1,4-BQ treatment could block 1,4-BQ-induced production of ROS and the occurrence of apoptosis. These results demonstrated that 1,4-BQ induced apoptosis in HL-60 cells through a ROS-dependent mitochondrial-mediated pathway.

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.

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.

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.

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.

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.

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.