Rigid Fe(III) Chelate with Phosphonate Pendants: A Stable and Effective Extracellular MRI Contrast Agent.

A novel Fe(III) complex, Fe-tBPCDTA, was synthesized and explored as a potential contrast agent for MRI. Compared to established agents like Fe-EDTA and Fe-tCDTA, Fe-tBPCDTA exhibited moderate relaxivity (r1 = 1.17 s-1·mmol-1) due to its enhanced second-sphere mechanism. It also displayed improved kinetic inertness, lower cytotoxicity, and enhanced redox stability. In vivo studies demonstrated its function as an extracellular fluid agent, providing tumor contrast comparable to that of Gd-DTPA at a higher dosage. Complete renal clearance occurred within 24 h. These findings suggest Fe-tBPCDTA as a promising candidate for further development as a safe and effective extracellular MRI contrast agent.

Adenosine A2A receptor antagonist SCH58261 improves the cognitive function in Alzheimer's disease model mice through activation of Nrf2 via an autophagy-dependent pathway.

AIMS: Adenosine, an important endogenous neuromodulator, contributes to a broad set of several neurodegenerative diseases. The adenosine A2A receptor (A2AR) is the most involved in neuropathological effects and plays an important role in the pathogenesis of Alzheimer's disease (AD). However, the effect of A2AR antagonist and the underlying mechanism in AD model mice remains unclear. RESULTS: The amyloid beta (Aß)1-42-induced mice AD models were used in this study. Several behavioral experiments were performed to evaluate the improvement of AD mice treat with A2AR receptor antagonist. For mechanism analysis, autophagy-related proteins, Kelch-like ECH-associated protein1(Keap1)- nuclear factor erythroid-derived factor 2-related factor (Nrf2) pathway activation and synaptic function were studied by using western blot, immunofluorescence (IF), immunohistochemistry (IHC), transmission electron microscope (TEM), real-time quantitative (PCR) and patch clamp. Pharmacological blockade of adenosine A2AR by SCH58261 (SCH) ameliorated cognitive deficits and decreased expression levels of several AD biomarkers, including Aß and hyperphosphorylation of Tau. Moreover, SCH activated the Nrf2 pathway through autophagy mediated Keap1 degradation, resulting in the improvement of neurons autophagy dysfunction, synaptic plasticity, and synaptic transmission. INNOVATION: Our data clarified that the SCH58261 (an antagonist of adenosine A2A receptor) could increase the level of autophagy, promote the ability of anti-oxidative stress by the activation of Keap1-Nrf2 pathway, and improve the synaptic function in Aß1-42-induced Alzheimer's disease mice or cell model, which provided a potential therapeutic strategy for AD. CONCLUSION: A2AR antagonism represents a promising strategy for the anti-AD agents development through autophagy-dependent pathway.

MiR-99a-3p downregulates TRIM21 to promote gastric cancer development.

Gastric cancer (GC) stands as one of the most formidable malignancies worldwide. It is well-established that miRNAs play a crucial role in the initiation and progression of various human cancers. Among these, miR-99a-3p has been implicated in the pathogenesis of GC. In the context of our study, we embarked on the comprehensive examination of miR-99a-3p expression in GC cells. Additionally, we sought to establish a correlation between miR-99a-3p expression levels and the overall survival (OS) of GC patients, and our findings hinted at its potential role in predicting an unfavorable prognosis. To further investigate the functional implications of miR-99a-3p in GC, we conducted a series of cell-based experiments after successfully knocking down miR-99a-3p. These investigations uncovered a substantial inhibition of cellular events associated with tumor progression. Moreover, employing TargetScan, we identified Tripartite motif-containing protein 21 (TRIM21) as a putative target with a binding site for miR-99a-3p. Subsequent dual-luciferase reporter gene assay confirmed the direct interaction between miR-99a-3p and TRIM21. Western blot analysis validated the alteration in TRIM21 expression levels, revealing an upregulation upon miR-99a-3p knockdown. Building on these molecular findings, we extended our investigations to human GC tissues, where we observed a downregulation of TRIM21, which, notably, correlated with shorter overall survival. Lastly, to further solidify our conclusions, we conducted a series of in vitro and in vivo rescue experiments, collectively suggesting that miR-99a-3p promoted the progression of GC cells through the downregulation of TRIM21. In summary, our study comprehensively explored the role of miR-99a-3p in GC, revealing its association with unfavorable patient outcomes, functional implications in tumor progression, and a direct regulatory relationship with TRIM21. These findings collectively underscore the significance of miR-99a-3p in the pathogenesis of GC and present a potential therapeutic avenue for further investigation.

Functional mechanism of hypoxia-like conditions mediating resistance to ferroptosis in cervical cancer cells by regulating KDM4A SUMOylation and the SLC7A11/GPX4 pathway.

The discovery of ferroptosis has unveiled new perspectives for cervical cancer (CC) management. We elucidated the functional mechanism of hypoxia-like conditions in CC cell ferroptosis resistance. CC cells were subjected to normoxia or hypoxia-like conditions, followed by erastin treatment to induce ferroptosis. The assessment of cell viability/ferroptosis resistance was performed by MTT assay/Fe2+, MDA, and glutathione measurement by colorimetry. KDM4A/SUMO1/Ubc9/SENP1 protein levels were determined by Western blot. Interaction and binding sites between KDM4A and SUMO1 were analyzed and predicted by immunofluorescence/co-immunoprecipitation and GPS-SUMO 1.0 software, with the target relationship verified by mutation experiment. SLC7A11/GPX4/H3K9me3 protein levels, and H3K9me3 level in the SLC7A11 gene promoter region were determined by RT-qPCR and Western blot/chromatin immunoprecipitation. H3H9me3/SLC7A11/GPX4 level alterations, and ferroptosis resistance after KDM4A silencing or KDM4A K471 mutation were assessed. Hypoxia-like conditions increased CC cell ferroptosis resistance and KDM4A, SUMO1, and Ubc9 protein levels, while it decreased SENP1 protein level. KDM4A and SUMO1 were co-localized in the nucleus, and hypoxia-like conditions promoted their interaction. Specifically, the K471 locus of KDM4A was the main locus for SUMO1ylation. Hypoxia-like conditions up-regulated SLC7A11 and GPX4 expression levels and decreased H3K9me3 protein level and H3K9me3 abundance in the SLC7A11 promoter region. KDM4A silencing or K471 locus mutation resulted in weakened interaction between KDM4A and SUMO1, elevated H3K9me3 levels, decreased SLC7A11 expression, ultimately, a reduced CC cell ferroptosis resistance. CoCl2-stimulated hypoxia-like conditions enhanced SUMO1 modification of KDM4A at the K471 locus specifically, repressed H3K9me3 levels, and up-regulated SLC7A11/GPX4 to enhance CC cell ferroptosis resistance.

Predicting response of hepatoblastoma primary lesions to neoadjuvant chemotherapy through contrast-enhanced computed tomography radiomics.

OBJECTIVE: To investigate the clinical value of contrast-enhanced computed tomography (CECT) radiomics for predicting the response of primary lesions to neoadjuvant chemotherapy in hepatoblastoma. METHODS: Clinical and CECT imaging data were retrospectively collected from 116 children with hepatoblastoma who received neoadjuvant chemotherapy. Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST). Subsequently, they were randomly stratified into a training cohort and a test cohort in a 7:3 ratio. The clinical model was constructed using univariate and multivariate logistic regression, while the radiomics model was developed based on selected radiomics features employing the support vector machine algorithm. The combined clinical-radiomics model incorporated both clinical and radiomics features. RESULTS: The area under the curve (AUC) for the clinical, radiomics, and combined models was 0.704 (95% CI: 0.563-0.845), 0.830 (95% CI: 0.704-0.959), and 0.874 (95% CI: 0.768-0.981) in the training cohort, respectively. In the validation cohort, the combined model achieved the highest mean AUC of 0.830 (95% CI 0.616-0.999), with a sensitivity, specificity, accuracy, precision, and f1 score of 72.0%, 81.1%, 78.5%, 57.2%, and 63.5%, respectively. CONCLUSION: CECT radiomics has the potential to predict primary lesion response to neoadjuvant chemotherapy in hepatoblastoma.

Risk factors associated with ototoxicity in long-term nasopharyngeal carcinoma survivors.

PURPOSE: To investigate patient-reported outcomes among long-term survivors and to analyze their associated risk factors to provide better treatment and symptom management for nasopharyngeal carcinoma patients. MATERIALS AND METHODS: This retrospective study collected patients diagnosed with nasopharyngeal carcinoma who received radical intensity-modulated radiotherapy in our hospital from June 2009 to June 2016. The patients' disease status and patient-reported outcomes were analyzed by follow-up. The ototoxicity was graded according to CTCAE 5.0. RESULTS: A total of 223 patients were included in the study. Among the enrolled patients, the median follow-up time was 8.4 (6.0-13.0) years. Based on the patient-reported outcomes, ototoxicity was the most common symptom (52.9 %). After univariable and multivariable logistic regression, age ≥ 50 years old (OR, 4.066; 95 % CI, 1.799-9.190; P = .001), diabetes (OR, 3.520; 95 % CI, 1.442-8.591; P = .006), D2 ≥ 69 Gy (OR, 3.715; 95 % CI, 1.064-12.969; P = . 040) and V35 ≥ 91.5 % (OR, 3.398; 95 % CI, 1.113-10.372; P = .032) were associated with a higher incidence of grade 3-4 ototoxicity. Then, we constructed the individual nomogram and the C index of the graph was 0.815. By univariable logistic regression, we found that grade 3-4 ototoxicity was associated with an increased risk of multiple other symptoms, dysmasesia, tongue dysfunction, hoarseness, dysphagia and ocular toxicity. CONCLUSION: In long-term survivors of nasopharyngeal carcinoma patients receiving IMRT, the most common patient-reported outcome was ototoxicity. Age ≥ 50 years, diabetes, ear exposure dose of D2 ≥ 69 Gy and V35 ≥ 91.5 % are independent risk factors for grade 3-4 ototoxicity.

An estrogen receptor α-derived peptide improves glucose homeostasis during obesity.

Estrogen receptor α (ERα) plays a crucial role in regulating glucose and energy homeostasis during type 2 diabetes mellitus (T2DM). However, the underlying mechanisms remain incompletely understood. Here we find a ligand-independent effect of ERα on the regulation of glucose homeostasis. Deficiency of ERα in the liver impairs glucose homeostasis in male, female, and ovariectomized (OVX) female mice. Mechanistic studies reveal that ERα promotes hepatic insulin sensitivity by suppressing ubiquitination-induced IRS1 degradation. The ERα 1-280 domain mediates the ligand-independent effect of ERα on insulin sensitivity. Furthermore, we identify a peptide based on ERα 1-280 domain and find that ERα-derived peptide increases IRS1 stability and enhances insulin sensitivity. Importantly, administration of ERα-derived peptide into obese mice significantly improves glucose homeostasis and serum lipid profiles. These findings pave the way for the therapeutic intervention of T2DM by targeting the ligand-independent effect of ERα and indicate that ERα-derived peptide is a potential insulin sensitizer for the treatment of T2DM.

[Evaluation of the feasibility of endoscopic tympanoplasty in two-person three-hand operation].

Objective:To study the difference of postoperative efficacy between two-person three-hand ear endoscopy and microscopic tympanoplasty in patients with chronic suppurative otitis media, and to explore the advantages and disadvantages of two-person three-hand ear endoscopy. Methods:A retrospective study was conducted on 100 patients who underwent tympanoplasty in the Department of Otolaryngology and Head and Neck Surgery of Hunan People's Hospital from April 2019 to March 2023, and they were divided into 2 groups with 50 cases each according to random number table method. Among them, 50 cases underwent endoscopic tympanoplasty in two-person three-hand（group A） and 50 cases underwent routine microscopic tympanoplasty（group B）. The operation and postoperative conditions of the two groups were followed up. Results:In group A, the mean operation time was（65.78±18.21） min, the mean intraoperative blood loss was（12.94±4.46） mL, the postoperative pain score was（1.82±0.60） points, and the mean postoperative hospital stay was（2.76±0.72） d. The mean operation time of group B was（89.45±20.38） min, the mean intraoperative blood loss was（22.78±5.74） mL, the postoperative pain score was（2.98±0.85） points, and the mean postoperative hospital stay was（3.82±0.75） d, which with statistical significance between the two groups（P<0.05）. Hearing in both groups was significantly improved 6 months after surgery, and the difference was statistically significant before and after surgery（P<0.05）, but there was no significant difference between the two groups before surgery and 6 months after surgery（P>0.05）. There were 2 cases in group A（4%） and 1 case in group B（2%） complicated with tympanic cord injury during operation, and the difference was not statistically significant（P>0.05）. There were 47 cases of A group（94%） of one-time healing of tympanic membrane after operation, 48 cases（96%） of group B, and the difference was not statistically significant（P>0.05）. Conclusion:There is no significant difference in cure rate and hearing improvement between two-person three-hand ear endoscopic tympanoplasty and conventional microscope surgery, and the operation time is significantly shortened, the amount of blood loss is less, and the postoperative recovery is faster. It has the advantages of clear operating field, two-person three-hand operation, minimally invasive, and can reach the range of middle ear tympanic sinus and mastoid apex, and the surgical complications are seldom, which is worth promoting.

Image-defined risk factors associated with MYCN oncogene amplification in neuroblastoma and their association with overall survival.

OBJECTIVE: The MYCN oncogene is a critical factor in the development and progression of neuroblastoma, and image-defined risk factors (IDRFs) are radiological findings used for the preoperative staging of neuroblastoma. This study aimed to investigate the specific categories of IDRFs associated with MYCN amplification in neuroblastoma and their association with overall survival. METHOD: A retrospective analysis was conducted on a cohort of 280 pediatric patients diagnosed with neuroblastoma, utilizing a combination of clinical and radiological data. MYCN amplification status was ascertained through molecular testing, and the assessment of IDRFs was conducted using either contrast-enhanced computed tomography or magnetic resonance imaging. The specific categories of IDRFs associated with MYCN amplification and their association with overall survival were analyzed. RESULTS: MYCN amplification was identified in 19.6% (55/280) of patients, with the majority of primary lesions located in the abdomen (53/55, 96.4%). Lesions accompanied by MYCN amplification exhibited significantly larger tumor volume and a greater number of IDRFs compared with those without MYCN amplification (P < 0.001). Both univariate and multivariate analyses revealed that coeliac axis/superior mesenteric artery encasement and infiltration of adjacent organs/structures were independently associated with MYCN amplification in abdominal neuroblastoma (P < 0.05). Patients presenting with more than four IDRFs experienced a worse prognosis (P = 0.017), and infiltration of adjacent organs/structures independently correlated with overall survival in abdominal neuroblastoma (P = 0.009). CONCLUSION: The IDRFs are closely correlated with the MYCN amplification status and overall survival in neuroblastoma.

Sex differences in luteinizing hormone aggravates Aß deposition in APP/PS1 and Aß1-42-induced mouse models of Alzheimer's disease.

Alzheimer's disease (AD) exhibits a higher incidence rate among older women, and dysregulation of the hypothalamic-pituitary-gonadal (HPG) axis during aging is associated with cognitive impairments and the development of dementia. luteinizing hormone (LH) has an important role in CNS function, such as mediating neuronal pregnenolone production, and modulating neuronal plasticity and cognition. The sex differences in LH and its impact on Aß deposition in AD individuals remain unclear, with no reported specific mechanisms. Here, we show through data mining that LH-related pathways are significantly enriched in female AD patients. Additionally, LH levels are elevated in female AD patients and exhibit a negative correlation with cognitive levels but a positive correlation with AD pathology levels, and females exhibit a greater extent of AD pathology, such as Aß deposition. In vivo, we observed that the exogenous injection of LH exacerbated behavioral impairments induced by Aß1-42 in mice. LH injection resulted in worsened neuronal damage and increased Aß deposition. In SH-SY5Y cells, co-administration of LH with Aß further exacerbated Aß-induced neuronal damage. Furthermore, LH can dose-dependently decrease the levels of NEP and LHR proteins while increasing the expression of GFAP and IBA1 in vivo and in vitro. Taken together, these results indicate that LH can exacerbate cognitive impairment and neuronal damage in mice by increasing Aß deposition. The potential mechanism may involve the reduction of NEP and LHR expression, along with the exacerbation of Aß-induced inflammation.

HER2 targeted therapy in colorectal Cancer: Current landscape and future directions.

Colorectal cancer (CRC) is one of the most common causes of tumor-related deaths globally. Despite recent improvements in the comprehensive therapy of malignancy, metastatic CRC continues to have a poor prognosis. Human epidermal growth factor receptor 2 (HER2) is an established oncogenic driver, which is successfully targeted for breast and gastric cancers. Approximately 5% of CRC patients carry somatic HER2 mutations or gene amplification. In 2019, the U.S. Food and Drug Administration have approved trastuzumab and pertuzumab in combination with chemotherapy for the treatment of HER2-positive metastatic CRC. This approval marked a significant milestone in the treatment of CRC, as HER2-positive patients now have access to targeted therapies that can improve their outcomes. Yet, assessment for HER2 overexpression/ amplification in CRC has not been standardized. The resistance mechanisms to anti-HER2 therapy have been not clearly investigated in CRC. Although many unknowns remain, an improved understanding of these anti-HER2 agents will be essential for advanced CRC. In this review, we provide an overview of the role of HER2 in CRC as an oncogenic driver, a prognostic and predictive biomarker, and a clinically actionable target, as well as the current progress and challenges in the field.

TRIM67 interacts with ENAH to regulate the apoptosis and autophagy of lung cancer cells.

The aim of this study was to further clarify the functional mechanism of the triangular 67 (TRIM67) gene in lung cancer cells. We detected the expression of TRIM67 in lung cancer cells by RT-qPCR and Western blot, transfected si-NC, si-TRIM67, and pcDNA-ENAH into the cells. The expression of TRIM67 and ENAH was detected by Western blot and immunofluorescence localization, and CO-IP and GST pull-down experiments verified the interaction. Flow cytometry, Western blot, and transmission electron microscopy (TEM) evaluated the apoptosis and autophagy levels. TRIM67 was highly expressed in lung cancer cell lines. Knockdown of TRIM67 promoted apoptosis and autophagy of A549 and NCI-H1299 cells. TRIM67 interacted with the ENAH protein. ENAH restored the effect of knocking down TRIM67 and further inhibited apoptosis and autophagy of A549 and NCI-H1299 cells. TRIM67 inhibits apoptosis and autophagy of lung cancer cells by interacting with ENAH.

Path planning algorithm for percutaneous puncture lung mass biopsy procedure based on the multi-objective constraints and fuzzy optimization.

Objective. The percutaneous puncture lung mass biopsy procedure, which relies on preoperative CT (Computed Tomography) images, is considered the gold standard for determining the benign or malignant nature of lung masses. However, the traditional lung puncture procedure has several issues, including long operation times, a high probability of complications, and high exposure to CT radiation for the patient, as it relies heavily on the surgeon's clinical experience.Approach.To address these problems, a multi-constrained objective optimization model based on clinical criteria for the percutaneous puncture lung mass biopsy procedure has been proposed. Additionally, based on fuzzy optimization, a multidimensional spatial Pareto front algorithm has been developed for optimal path selection. The algorithm finds optimal paths, which are displayed on 3D images, and provides reference points for clinicians' surgical path planning.Main results.To evaluate the algorithm's performance, 25 data sets collected from the Second People's Hospital of Zigong were used for prospective and retrospective experiments. The results demonstrate that 92% of the optimal paths generated by the algorithm meet the clinicians' surgical needs.Significance.The algorithm proposed in this paper is innovative in the selection of mass target point, the integration of constraints based on clinical standards, and the utilization of multi-objective optimization algorithm. Comparison experiments have validated the better performance of the proposed algorithm. From a clinical standpoint, the algorithm proposed in this paper has a higher clinical feasibility of the proposed pathway than related studies, which reduces the dependency of the physician's expertise and clinical experience on pathway planning during the percutaneous puncture lung mass biopsy procedure.

Effect of Personality and Pain Catastrophizing on Postoperative Analgesia Following Cesarean Section: A Prospective Cohort Study.

Purpose: This study aimed to investigate the effects of different psychological personalities and pain catastrophizing levels on postoperative analgesia in patients undergoing cesarean section. Patients and Methods: Puerperas who underwent cesarean section at our hospital between January and August 2023 were recruited into the study and assessed using the Eysenck Personality Questionnaire-Revised Short Scale (EPQRSC) and Pain Catastrophizing Scale (PCS). Data on the numerical pain intensity at rest and during activity 24 h after surgery, number and dosage of analgesia pumps, and satisfaction with analgesia were recorded. According to the numerical pain score during activity 24 h post-operation, the patients were divided into the analgesia incomplete group (≥4) and control group (<4). Univariate analysis, Spearman correlation analysis, and binary logistic regression analysis were used to evaluate the influence of personality characteristics and PCS on postoperative analgesia. Results: A total of 778 women were included in the study. The incidence of inadequate analgesia was 89.8%. The satisfaction rate of analgesia was 66.8%. Univariate analysis showed that extraversion; neuroticism; PCS; numbers of previous cesarean delivery; ASA; analgesic satisfaction; and 24-h analgesia pump compressions and dosage were associated with postoperative analgesia after cesarean section (P<0.05). Using binary logistic regression analysis, the first cesarean section (odds ratio [OR]=0.056, 95% confidence interval [CI]=1.913-19.174), the number of 24-h analgesic pump compressions (OR=8.464, 95% CI=0.356-0.604), extraversion (OR=0.667, 95% CI=0.513-0.866), neuroticism (OR=1.427, 95% CI=1.104-1.844), and PCS (OR=7.718, 95% CI=0.657-0.783) were factors affecting postoperative analgesia. Conclusion: The incidence of inadequate analgesia after a cesarean section was high (89.8% on the first day after surgery). Formulating accurate analgesia programs for women undergoing cesarean section with extraversion, neuroticism personality characteristics, and pain catastrophizing behaviors is necessary for improving their postoperative analgesia effects and satisfaction and promoting postpartum comfort.

CT radiomics to differentiate between Wilms tumor and clear cell sarcoma of the kidney in children.

BACKGROUND: To investigate the role of CT radiomics in distinguishing Wilms tumor (WT) from clear cell sarcoma of the kidney (CCSK) in pediatric patients. METHODS: We retrospectively enrolled 83 cases of WT and 33 cases of CCSK. These cases were randomly stratified into a training set (n = 81) and a test set (n = 35). Several imaging features from the nephrographic phase were analyzed, including the maximum tumor diameter, the ratio of the maximum CT value of the tumor solid portion to the mean CT value of the contralateral renal vein (CTmax/CT renal vein), and the presence of dilated peritumoral cysts. Radiomics features from corticomedullary phase were extracted, selected, and subsequently integrated into a logistic regression model. We evaluated the model's performance using the area under the curve (AUC), 95% confidence interval (CI), and accuracy. RESULTS: In the training set, there were statistically significant differences in the maximum tumor diameter (P = 0.021) and the presence of dilated peritumoral cysts (P = 0.005) between WT and CCSK, whereas in the test set, no statistically significant differences were observed (P > 0.05). The radiomics model, constructed using four radiomics features, demonstrated strong performance in the training set with an AUC of 0.889 (95% CI: 0.811-0.967) and an accuracy of 0.864. Upon evaluation using fivefold cross-validation in the training set, the AUC remained high at 0.863 (95% CI: 0.774-0.952), with an accuracy of 0.852. In the test set, the radiomics model achieved an AUC of 0.792 (95% CI: 0.616-0.968) and an accuracy of 0.857. CONCLUSION: CT radiomics proves to be diagnostically valuable for distinguishing between WT and CCSK in pediatric cases.

Modular access to chiral bridged piperidine-γ-butyrolactones via catalytic asymmetric allylation/aza-Prins cyclization/lactonization sequences.

Chiral functionalized piperidine and lactone heterocycles are widely spread in natural products and drug candidates with promising pharmacological properties. However, there remains no general asymmetric methodologies that enable rapid assemble both critical biologically important units into one three-dimensional chiral molecule. Herein, we describe a straightforward relay strategy for the construction of enantioenriched bridged piperidine-γ-butyrolactone skeletons incorporating three skipped stereocenters via asymmetric allylic alkylation and aza-Prins cyclization/lactonization sequences. The excellent enantioselectivity control in asymmetric allylation with the simplest allylic precursor is enabled by the synergistic Cu/Ir-catalyzed protocol; the success of aza-Prins cyclization/lactonization can be attributed to the pivotal role of the ester substituent, which acts as a preferential intramolecular nucleophile to terminate the aza-Prins intermediacy of piperid-4-yl cation species. The resulting chiral piperidine-γ-butyrolactone bridged-heterocyclic products show impressive preliminary biological activities against a panel of cancer cell lines.

Identification of an Ultra-High-Risk Subgroup of Neuroblastoma Patients within the High-Risk Cohort Using a Computed Tomography-Based Radiomics Approach.

RATIONALE AND OBJECTIVES: To identify ultra-high-risk (UHR) neuroblastoma patients who experienced disease-related mortality within 18 months of diagnosis within the high-risk cohort using computed tomography (CT)-based radiomics analysis. MATERIALS AND METHODS: A retrospective analysis was conducted on 105 high-risk neuroblastoma patients, divided into a training set (n = 74) and a test set (n = 31). Radiomics features were extracted and selected from arterial phase CT images, and an optimal radiomics signature was established using the support vector machine algorithm. Evaluation metrics, including area under the curve (AUC) and 95% confidence interval (CI), were calculated. Furthermore, the fit and clinical benefit of the signature, along with its correlation with overall survival (OS), were analyzed. RESULTS: The optimal radiomics signature comprised 11 features. In the training set, AUC and accuracy were 0.911 (95% CI: 0.840-0.982) and 0.892, respectively. In the test set, AUC and accuracy were 0.828 (95% CI: 0.669-0.987) and 0.839, respectively. There was no significant difference between predicted probability and actual probability, and the signature demonstrated net benefit. The concordance index of this signature for predicting OS was 0.743 (95% CI: 0.672-0.814) in the training set and 0.688 (95% CI: 0.566-0.810) in the test set. Moreover, the signature achieved AUC values of 0.832, 0.863, and 0.721 for 1-year, 2-year, and 3-year OS in the training set, and 0.870, 0.836, and 0.638 in the test set for the respective time periods. CONCLUSION: The utilization of CT-based radiomics signature to identify an UHR subgroup of neuroblastoma patients within the high-risk cohort can help aid in predicting early disease progression.

Application of dual-energy CT with prospective ECG-gating in cardiac CT angiography for children: Radiation and contrast agent dose.

OBJECTIVE: This research aimed to investigate the feasibility of utilizing dual-energy CT virtual monoenergetic images (VMI1) with prospective electrocardiogram (ECG2) gating for reducing radiation and contrast agent doses in pediatric patients with congenital heart disease (CHD3). METHODS: There were 100 pediatric patients with CHD included in this study. Group A (n = 50) underwent dual-energy scanning with prospective ECG-gating, and group B (n = 50) underwent conventional scanning with retrospective ECG-gating. Comparative analysis of CT values of lumen, objective image quality assessment, subjective image quality evaluations, and diagnostic efficacy were performed. RESULTS: CT values, image noise, signal-to-noise ratio (SNR4), and contrast-to-noise ratio (CNR5) were significantly affected by the VMI energy level, and they all increased with decreasing energy levels (P > 0.05). Combining subjective evaluation, the 45 keV VMI was considered the optimum image in group A. The 45 keV VMI exhibited higher CT values of lumen compared to conventional scanning images (P < 0.003 âˆ¼ 0.836), but meanwhile, the image noise was also higher in the 45 keV VMI (P = 0.004). Differences between the two groups in SNR, CNR, and diagnostic accuracy were not statistically significant. Compared to group B, the 45 keV VMI showed fewer contrast-induced artifacts (P < 0.001) and higher image quality score (P = 0.037). Group A had a 64 % reduction in radiation dose and a 40 % decrease in iodine dose compared to group B. CONCLUSION: The combination of dual-energy CT with prospective ECG-gating reduces radiation and iodine doses in pediatric patients with CHD. The 45 keV VMI can provide clinically acceptable image quality while declining contrast agent artifacts.

Copper/Ruthenium Relay Catalysis for Stereodivergent Access to δ-Hydroxy α-Amino Acids and Small Peptides.

An atom- and step-economical and redox-neutral cascade reaction enabled by asymmetric bimetallic relay catalysis by merging a ruthenium-catalyzed asymmetric borrowing-hydrogen reaction with copper-catalyzed asymmetric Michael addition has been realized. A variety of highly functionalized 2-amino-5-hydroxyvaleric acid esters or peptides bearing 1,4-non-adjacent stereogenic centers have been prepared in high yields with excellent enantio- and diastereoselectivity. Judicious selection and rational modification of the Ru catalysts with careful tuning of the reaction conditions played a pivotal role in stereoselectivity control as well as attenuating undesired α-epimerization, thus enabling a full complement of all four stereoisomers that were otherwise inaccessible in previous work. Concise asymmetric stereodivergent synthesis of the key intermediates for biologically important chiral molecules further showcases the synthetic utility of this methodology.