Single-cell transcriptomic analysis reveals that the APP-CD74 axis promotes immunosuppression and progression of testicular tumors.

Testicular tumors represent the most common malignancy among young men. Nevertheless, the pathogenesis and molecular underpinning of testicular tumors remain largely elusive. We aimed to delineate the intricate intra-tumoral heterogeneity and the network of intercellular communication within the tumor microenvironment. A total of 40,760 single-cell transcriptomes were analyzed, encompassing samples from six individuals with seminomas, two patients with mixed germ cell tumors, one patient with a Leydig cell tumor, and three healthy donors. Five distinct malignant subclusters were identified in the constructed landscape. Among them, malignant 1 and 3 subclusters were associated with a more immunosuppressive state and displayed worse disease-free survival. Further analysis identified that APP-CD74 interactions were significantly strengthened between malignant 1 and 3 subclusters and 14 types of immune subpopulations. In addition, we established an aberrant spermatogenesis trajectory and delineated the global gene alterations of somatic cells in seminoma testes. Sertoli cells were identified as the somatic cell type that differed the most from healthy donors to seminoma testes. Cellular communication between spermatogonial stem cells and Sertoli cells is disturbed in seminoma testes. Our study delineates the intra-tumoral heterogeneity and the tumor immune microenvironment in testicular tumors, offering novel insights for targeted therapy. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

The clinical efficacy of a daratumumab-based regimen in relapsed/refractory acute leukemia: a single-center experience.

Relapsed/refractory acute leukemia (R/R-AL) is associated with a low remission rate, short survival rate, and poor prognosis. Treating R/R-AL remains challenging as there is no standardized effective regimen; hence, there is a need for efficient therapies. CD38 expression has been observed in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Daratumumab is a humanized anti-CD38 monoclonal antibody used to treat multiple myeloma and has been reported to treat R/R-AL safely and effectively. The clinical data of 10 adult patients with R/R-AL who were treated with a daratumumab-based salvage regimen between July 2018 and May 2023 at our center were analyzed retrospectively. Seven AML and three ALL cases were included in the analysis. Seven (70%) patients showed responses to the treatments (complete response [CR], 60%; partial response [PR], 10%). Of the seven responders, three underwent allogenic stem cell transplantation (ASCT), including one who underwent a second ASCT. Among the five patients with R/R AML who had prior exposure to venetoclax, three achieved a therapeutic response (two CR and one PR) when re-treated with venetoclax in combination with daratumumab. The median follow-up time was 6.15 months (0.9-21 months). Overall survival and event-free survival rates at 12 months were 68.6% and 40.0%, respectively. The main adverse events included grade 3 febrile neutropenia (20%) and grade 3 hematological toxicities (60%). The daratumumab-based salvage regimen offers patients with R/R-AL the opportunity of remission with acceptable tolerability, creating the possibility of bridging ASCT.

Transverse interlaminar ultrasound-guided C1-C2 puncture for the intrathecal administration of nusinersen in patients with spinal muscular atrophy.

INTRODUCTION/AIMS: Severe spinal deformities and previous spinal orthopedic instrumentation may result in substantial technical challenges for nusinersen delivery through lumbar puncture in patients with spinal muscular atrophy (SMA). The aim of this paper was to review our experience with ultrasound-guided cervical puncture as an alternative approach for the intrathecal administration of nusinersen. METHODS: This was a retrospective medical record review of transverse interlaminar ultrasound-guided C1-C2 puncture for nusinersen delivery in SMA patients. The details of puncture, complications, and success rate of the procedure were summarized. RESULTS: There were four patients who received a total of 13 cervical punctures for nusinersen delivery. All procedures were technically successful with no major complications. Full doses of nusinersen were delivered intrathecally. DISCUSSION: Transverse interlaminar ultrasound-guided C1-C2 puncture is an alternative approach for administering nusinersen if lumbar puncture fails. The success of the technique requires a thorough preprocedural evaluation of cervical spine imaging, sound knowledge of the cervical sonoanatomy and careful manipulation of the needle.

Biological characteristics related to treatment effects of the levonorgestrel-releasing intrauterine system on adenomyosis-associated dysmenorrhoea.

RESEARCH QUESTION: Are there correlations between the biological expression of steroid receptors and the extent of fibrosis in adenomyotic lesions, and the treatment effectiveness of the levonorgestrel-releasing intrauterine system (LNG-IUS) on alleviation of adenomyosis-associated dysmenorrhoea. DESIGN: In this retrospective cohort study, 125 women with adenomyosis who underwent hysterectomy were screened. Tissue samples were collected from 41 patients who had undergone LNG-IUS treatment prior to surgery, and these patients were further categorized into the treatment effective group (n = 18) and the treatment failure group (n = 23) according to their self-reported relief from dysmenorrhoea after 6 months of treatment. Oestrogen receptor-α (ER-α) and progesterone receptor expression, and the extent of fibrosis in the adenomyotic lesions were measured using immunohistochemistry and Masson's trichrome staining, respectively. RESULTS: Patients in the treatment failure group demonstrated lower expression of ER-α and progesterone receptors, and more pronounced fibrosis in the stroma of adenomyotic lesions compared with patients in the treatment effective group. In the glandular epithelium of lesions, ER-α expression was reduced significantly in the treatment failure group, whereas no notable difference in the expression of progesterone receptors was observed. Notably, the staining intensity of ER-α in the stroma of lesions was found to have the strongest positive correlation with the degree of symptom alleviation for dysmenorrhoea (r = 0.703, P < 0.001), with an area under the curve of 0.894 for prediction. CONCLUSIONS: The reduced expression of steroid receptors in adenomyotic lesions, especially ER-α in the stroma, was associated with increased likelihood of treatment failure of LNG-IUS for alleviation of dysmenorrhoea.

In vitro and in vivo study of antibacterial and anti-encrustation coating on ureteric stents.

OBJECTIVES: To investigate the ability of propolis-coated ureteric stents to solve complications, especially urinary tract infections (UTIs) and crusting, in patients with long-term indwelling ureteric stents through antimicrobial and anti-calculus activities. MATERIALS AND METHODS: Polyurethane (PU) ureteric stents were immersed in the ethanol extract of propolis (EEP), a well-known antimicrobial honeybee product, and subjected to chemical, hydrophilic, and seismic tests. The antimicrobial activity of the EEP coating was then examined by in vitro investigation. Proteus mirabilis infection was induced in rats within uncoated and EEP-coated groups, and the infection, stone formation, and inflammation were monitored at various time points. RESULTS: The characterisation results showed that the hydrophilicity and stability of the EEP surface improved. In vitro tests revealed that the EEP coating was biocompatible, could eliminate >90% of bacteria biofilms attached to the stent and could maintain bacteriostatic properties for up to 3 months. The in vivo experiment revealed that the EEP-coating significantly reduced the amount of bacteria, stones, and salt deposits on the surface of the ureteric stents and decreased inflammation in the host tissue. CONCLUSIONS: Compared with clinically used PU stents, EEP-coated ureteric stents could better mitigate infections and prevent encrustation. Thus, this study demonstrated that propolis is a promising natural dressing material for ureteric stents.

iHerd: an integrative hierarchical graph representation learning framework to quantify network changes and prioritize risk genes in disease.

Different genes form complex networks within cells to carry out critical cellular functions, while network alterations in this process can potentially introduce downstream transcriptome perturbations and phenotypic variations. Therefore, developing efficient and interpretable methods to quantify network changes and pinpoint driver genes across conditions is crucial. We propose a hierarchical graph representation learning method, called iHerd. Given a set of networks, iHerd first hierarchically generates a series of coarsened sub-graphs in a data-driven manner, representing network modules at different resolutions (e.g., the level of signaling pathways). Then, it sequentially learns low-dimensional node representations at all hierarchical levels via efficient graph embedding. Lastly, iHerd projects separate gene embeddings onto the same latent space in its graph alignment module to calculate a rewiring index for driver gene prioritization. To demonstrate its effectiveness, we applied iHerd on a tumor-to-normal GRN rewiring analysis and cell-type-specific GCN analysis using single-cell multiome data of the brain. We showed that iHerd can effectively pinpoint novel and well-known risk genes in different diseases. Distinct from existing models, iHerd's graph coarsening for hierarchical learning allows us to successfully classify network driver genes into early and late divergent genes (EDGs and LDGs), emphasizing genes with extensive network changes across and within signaling pathway levels. This unique approach for driver gene classification can provide us with deeper molecular insights. The code is freely available at https://github.com/aicb-ZhangLabs/iHerd. All other relevant data are within the manuscript and supporting information files.

Prognostic value of right ventricular trabecular complexity in patients with arrhythmogenic cardiomyopathy.

OBJECTIVES: The present study aimed to investigate the incremental prognostic value of the right ventricular fractal dimension (FD), a novel marker of myocardial trabecular complexity by cardiac magnetic resonance (CMR) in patients with arrhythmogenic cardiomyopathy (ACM). METHODS: Consecutive patients with ACM undergoing CMR were followed up for major cardiac events, including sudden cardiac death, aborted cardiac arrest, and appropriate implantable cardioverter defibrillator intervention. Prognosis prediction was compared by Cox regression analysis. We established a multivariable model supplemented with RV FD and evaluated its discrimination by Harrell's C-statistic. We compared the category-free, continuous net reclassification improvement (cNRI) and integrated discrimination index (IDI) before and after the addition of FD. RESULTS: A total of 105 patients were prospectively included from three centers and followed up for a median of 60 (48, 66) months; experienced 36 major cardiac events were recorded. Trabecular FD displayed a strong unadjusted association with major cardiac events (p < 0.05). In the multivariable Cox regression analysis, RV maximal apical FD maintained an independent association with major cardiac events (hazard ratio, 1.31 (1.11-1.55), p < 0.002). The Hosmer-Lemeshow goodness of fit test displayed good fit (X2 = 0.68, p = 0.99). Diagnostic performance was significantly improved after the addition of RV maximal apical FD to the multivariable baseline model, and the continuous net reclassification improvement increased 21% (p = 0.001), and the integrated discrimination index improved 16% (p = 0.045). CONCLUSIONS: In patients with ACM, CMR-assessed myocardial trabecular complexity was independently correlated with adverse cardiovascular events and provided incremental prognostic value. CLINICAL RELEVANCE STATEMENT: The application of FD values for assessing RV myocardial trabeculae may become an accessible and promising parameter in monitoring and early diagnosis of risk factors for adverse cardiovascular events in patients with ACM. KEY POINTS: • Ventricular trabecular morphology, a novel quantitative marker by CMR, has been explored for the first time to determine the severity of ACM. • Patients with higher maximal apical fractal dimension of RV displayed significantly higher cumulative incidence of major cardiac events. • RV maximal apical FD was independently associated with major cardiac events and provided incremental prognostic value in patients with ACM.

14-3-3-η interacts with BCL-2 to protect human endothelial progenitor cells from ox-LDL-triggered damage.

Oxidized low-density lipoprotein (ox-LDL) causes dysfunction of endothelial progenitor cells (EPCs), and we recently reported that 14-3-3-η can attenuate the damage triggered by ox-LDL in EPCs. However, the molecular mechanisms by which 14-3-3-η protects EPCs from the damage caused by ox-LDL are not fully understood. In this study, we observed that the expression of 14-3-3-η and BCL-2 were downregulated in ox-LDL-treated EPCs. Overexpression of 14-3-3-η in ox-LDL-treated EPC significantly increased BCL-2 level, while knockdown of BCL-2 reduced 14-3-3-η expression and mitigated the protective effect of 14-3-3-η on EPCs. In addition, we discovered that 14-3-3-η colocalizes and interacts with BCL-2 in EPCs. Taken together, these data suggest that 14-3-3-η protects EPCs from ox-LDL-induced damage by its interaction with BCL-2.

Insights into the Acceleration Mechanism of Intracellular N and Fe Co-doped Carbon Dots on Anaerobic Denitrification Using Proteomics and Metabolomics Techniques.

Bulk carbon-based materials can enhance anaerobic biodenitrification when they are present in extracellular matrices. However, little information is available on the effect of nitrogen and iron co-doped carbon dots (N, Fe-CDs) with sizes below 10 nm on this process. This work demonstrated that Fe-NX formed in N, Fe-CDs and their low surface potentials facilitated electron transfer. N, Fe-CDs exhibited good biocompatibility and were effectively absorbed by Pseudomonas stutzeri ATCC 17588. Intracellular N, Fe-CDs played a dominant role in enhancing anaerobic denitrification. During this process, the nitrate removal rate was significantly increased by 40.60% at 11 h with little nitrite and N2O accumulation, which was attributed to the enhanced activities of the electron transport system and various denitrifying reductases. Based on proteomics and metabolomic analysis, N, Fe-CDs effectively regulated carbon/nitrogen/sulfur metabolism to induce more electron generation, less nitrite/N2O accumulation, and higher levels of nitrogen removal. This work reveals the mechanism by which N, Fe-CDs enhance anaerobic denitrification and broaden their potential application in nitrogen removal.

Bladder endometriosis: symptoms and pregnancy outcomes.

OBJECTIVE: To investigate the clinical features of bladder endometriosis and factors associated with urinary symptoms, pregnancy outcomes, and long-term effects of symptom relief and recurrence. DESIGN: A single-center retrospective cohort study. SETTING: A tertiary referral hospital. PARTICIPANTS: Forty-seven patients who were surgically confirmed to have bladder endometriosis at Peking Union Medical College Hospital between January 2012 and December 2023 were included in this study. INTERVENTIONS: A retrospective study of the clinical and pathological features and reproductive outcomes in patients with bladder endometriosis. MEASUREMENTS AND MAIN RESULTS: Among 47 patients with bladder endometriosis, 27 (57.4%) presented with urinary symptoms, including urinary frequency, urgency, dysuria, and hematuria. Patients with urinary symptoms were more likely to have previous cesarean sections (odds ratio [OR] 4.5, 95% confidence interval [CI] 1.1-19.2, p=0.032) and experience dysmenorrhea compared to those without (p=0.008, OR 5.3, 95%CI 1.5-18.8). Anterior compartment obliteration was another factor associated with urinary symptoms (OR 7.2, 95%CI 1.3-40.4, p=0.016). Bladder lesions located within 1 cm of the ureteral orifice (OR 7.2, 95%CI 1.3-40.4, p=0.020) and the deeper invasive layer of lesions (mucosal layer, OR 6.1, 95%CI 1.4-25.8, p=0.009) were also found to be associated with symptoms. Regarding reproductive outcomes, 12 patients desired to conceive. Of the patients who desired pregnancy, 66.7% achieved pregnancy; 5 spontaneously and 3 after IVF treatment. The miscarriage rate among patients with bladder endometriosis was 25.0% in the age range of 27-40 years. Additionally, all patients experienced symptom relief after one year of follow-up. Only two patients experienced bladder endometriosis recurrence. CONCLUSIONS: Previous cesarean section, dysmenorrhea, anterior compartment obliteration, lesion in the trigone, and mucosal layer invasion were identified as factors associated with urinary symptoms. Although some patients conceived successfully after surgery, disentangling the independent effect of bladder endometriosis on fertility remains challenging.

Long-term efficacy and safety of levonorgestrel releasing intrauterine system in the treatment of adenomyosis: evidence mapping.

PURPOSE: To summarize evidence on levonorgestrel releasing intrauterine system (LNG-IUS) in the treatment of adenomyosis (AM) and to identify potential research gaps. METHODS: Search was conducted in MEDLINE, The Cochrane Library, EMBASE, CBM, CNKI, and Wanfang. We included studies investigating patients with AM treated with LNG-IUS combined with conservative therapy. RESULTS: Thirty-nine studies compared LNG-IUS with other conservative therapeutic drugs. The most common comparison was GnRH-a + LNG-IUS vs. LNG-IUS alone, followed by LNG-IUS vs. mifepristone, expected treatment, and GnRH-a. GnRH-a + LNG-IUS was more beneficial in reducing the intensity of dysmenorrhea than LNG-IUS alone at the 6-month follow-up in patients with an enlarged uterus and moderate to severe dysmenorrhea. Large and well-designed studies are needed to confirm the efficacy of LNG-IUS and GnRH-a on reducing uterine volume at 6-month follow-up. Thirty-two studies investigated LNG-IUS as the postoperative management. The most common comparison was surgical excision + LNG-IUS vs. surgical excision. Results showed VAS scores were lower in the surgical excision + LNG-IUS group than in the surgical excision group at the 1-year follow-up. Evidence on endometrial thickness, quality of life, adverse events and beneficial effect at 3 and 5 years are needed. CONCLUSIONS: Combined GnRH-a and LNG-IUS treatment was more efficacious than LNG-IUS alone for patients with an enlarged uterus and moderate to severe dysmenorrhea. Moreover, LNG-IUS seemed to show potential long-term benefits in postoperative therapy, warranting further meta-analysis for confirmation.

Intelligent Detection Method of Atrial Fibrillation by CEPNCC-BiLSTM Based on Long-Term Photoplethysmography Data.

Atrial fibrillation (AF) is the most prevalent arrhythmia characterized by intermittent and asymptomatic episodes. However, traditional detection methods often fail to capture the sporadic and intricate nature of AF, resulting in an increased risk of false-positive diagnoses. To address these challenges, this study proposes an intelligent AF detection and diagnosis method that integrates Complementary Ensemble Empirical Mode Decomposition, Power-Normalized Cepstral Coefficients, Bi-directional Long Short-term Memory (CEPNCC-BiLSTM), and photoelectric volumetric pulse wave technology to enhance accuracy in detecting AF. Compared to other approaches, the proposed method demonstrates faster preprocessing efficiency and higher sensitivity in detecting AF while effectively filtering out false alarms from photoplethysmography (PPG) recordings of non-AF patients. Considering the limitations of conventional AF detection evaluation systems that lack a comprehensive assessment of efficiency and accuracy, this study proposes the ET-score evaluation system based on F-measurement, which incorporates both computational speed and accuracy to provide a holistic assessment of overall performance. Evaluated with the ET-score, the CEPNCC-BiLSTM method outperforms EEMD-based improved Power-Normalized Cepstral Coefficients and Bi-directional Long Short-term Memory (EPNCC-BiLSTM), Support Vector Machine (SVM), EPNCC-SVM, and CEPNCC-SVM methods. Notably, this approach achieves an outstanding accuracy rate of up to 99.2% while processing PPG recordings within 5 s, highlighting its potential for long-term AF monitoring.

Early Diagnosis and Treatment of Kidney Injury: A Focus on Urine Protein.

The kidney, an essential excretory organ of the body, performs a series of crucial physiological functions such as waste removal, maintenance of electrolyte and acid-base balance, and endocrine regulation. Due to its rich blood flow and high metabolic activity, the kidney is susceptible to damage. Currently, kidney injury is classified into acute kidney injury (AKI) and chronic kidney disease (CKD), both of which are associated with high rates of morbidity and mortality on a global scale. The current clinical diagnosis of renal injury relies on the assessment of renal filtration function using creatinine and urea nitrogen as "gold-standard" markers. However, the delayed response time, limited specificity, and reduced accuracy of creatinine and urea nitrogen in evaluating kidney injury have significantly hindered advancements in diagnostic methods for kidney injury. Urinary protein is widely utilized as a biomarker for the early diagnosis of kidney injury due to the selectivity of the glomerular filtration system determining whether proteins can pass through the filtration barrier based on their size and charge. Therefore, as a complex biological sample with varying charges and particle sizes, urinary protein is considered an ideal indicator for monitoring the progression of kidney disease. Exploring the relationship between urinary protein and the advancement of kidney injury based on differences in particle size and charge offers a new perspective for assessing and treating such injuries. Hence, we conducted a comprehensive review of 74 relevant studies to gain a thorough understanding of the physiological mechanism and significance of proteinuria production. The aim was to explore the challenges and opportunities in clinical urine protein detection, as well as to discuss strategies targeting glomerular filtration barriers in order to effectively reduce urine protein levels and treat kidney injury, which could provide a new perspective for identifying the progression of kidney injury.

Using Transcriptomics to Determine the Mechanism for the Resistance to Fusarium Head Blight of a Wheat-Th. elongatum Translocation Line.

Fusarium head blight (FHB), caused by the Fusarium graminearum species complex, is a destructive disease in wheat worldwide. The lack of FHB-resistant germplasm is a barrier in wheat breeding for resistance to FHB. Thinopyrum elongatum is an important relative that has been successfully used for the genetic improvement of wheat. In this study, a translocation line, YNM158, with the YM158 genetic background carrying a fragment of diploid Th. elongatum 7EL chromosome created using 60Co-γ radiation, showed high resistance to FHB under both field and greenhouse conditions. Transcriptome analysis confirmed that the horizontal transfer gene, encoding glutathione S-transferase (GST), is an important contributor to FHB resistance in the pathogen infection stage, whereas the 7EL chromosome fragment carries other genes regulated by F. graminearum during the colonization stage. Introgression of the 7EL fragment affected the expression of wheat genes that were enriched in resistance pathways, including the phosphatidylinositol signaling system, protein processing in the endoplasmic reticulum, plant-pathogen interaction, and the mitogen-activated protein kinase (MAPK) signaling pathway at different stages after F. graminearium infection. This study provides a novel germplasm for wheat resistance to FHB and new insights into the molecular mechanisms of wheat resistance to FHB.

[Perioperative nursing for patients undergoing autologous dermis grafting for penile girth augmentation and penile lengthening].

OBJECTIVE: To explore the perioperative nursing methods of autologous dermal transplantation for penile girth enhancement combined with penile lengthening surgery. METHODS: Summarize the perioperative nursing data of 5 patients with small penis who underwent autologous groin dermal transplantation for penile girth enhancement combined with penile lengthening surgery. RESULTS: After comprehensive perioperative nursing, all 5 patients recovered well after the surgery. The preoperative APPSSI scores of the patients were 4.60±0.48, which were all less than 6 points. The postoperative APPSSI scores at 2 months, 6 months, and 12 months were 9－12 (10.6±1.02), 10－12 (11.2±0.98), and 10－12 (11.2±0.98) respectively, showing satisfaction with the surgical outcomes. There was a statistically significant difference compared to the preoperative APPSSI scores (ï¼°<0.05). The preoperative SAS scores were 45－58 (52.2±4.35), and the SAS scores at 2 months, 6 months, and 12 months postoperatively were 31－40 (34.2±3.31), 30-41 (35.8±3.65), and 33－40 (35.6±2.33) respectively, indicating a reduction in anxiety levels after the surgery, with a statistically significant difference compared to the preoperative SAS scores (P<0.05). The preoperative IIEF-5 scores were 7－15 (10.4±2.87), and the IIEF-5 scores at 2 months, 6 months, and 1 year postoperatively were 16－24 (19.8±2.71), 18－25 (21.2±2.48), and 18－24 (20.8±2.39) respectively, showing a significant improvement postoperatively, with statistical significance (P<0.05). The preoperative NPTR examination showed a sustained erection time of 18－25 (21.2±2.59) minutes, and the NPTR examination at 2 months, 6 months, and 1 year postoperatively showed sustained erection times of 18－24 (21.8±2.28), 20-25 (23.4±2.30), and 24－27 (25.4±1.14) minutes respectively. There was no statistically significant difference in the sustained erection time at 2 months and 6 months postoperatively compared to preoperative NPTR examination, but there was a statistically significant difference at 12 months postoperatively (P<0.01). CONCLUSION: Comprehensive perioperative nursing is an important factor in achieving high satisfaction with the surgery, promoting postoperative recovery, and improving the quality of sexual life for patients undergoing autologous groin dermal transplantation for penile girth enhancement combined with penile lengthening surgery.

A non-metal single atom nanozyme for cutting off the energy and reducing power of tumors.

Enzymes are considered safe and effective therapeutic tools for various diseases. With the increasing integration of biomedicine and nanotechnology, artificial nanozymes offer advanced controllability and functionality in medical design. However, several notable gaps, such as catalytic diversity, specificity and biosafety, still exist between nanozymes and their native counterparts. Here we report a non-metal single-selenium (Se)-atom nanozyme (SeSAE), which exhibits potent nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-mimetic activity. This novel single atom nanozyme provides a safe alternative to conventional metal-based catalysts and effectively cuts off the cellular energy and reduction equivalents through its distinctive catalytic function in tumors. In this study, we have demonstrated the substantial efficacy of SeSAE as an antitumor nanomedicine across diverse mouse models without discernible systemic adverse effects. The mechanism of the NADPH oxidase-like activity of the non-metal SeSAE was rationalized by density functional theory calculations. Furthermore, comprehensive elucidation of the biological functions, cell death pathways, and metabolic remodeling effects of the nanozyme was conducted, aiming to provide valuable insights into the development of single atom nanozymes with clinical translation potential.

Attention-based deep learning for breast lesions classification on contrast enhanced spectral mammography: a multicentre study.

BACKGROUND: This study aims to develop an attention-based deep learning model for distinguishing benign from malignant breast lesions on CESM. METHODS: Preoperative CESM images of 1239 patients, which were definitely diagnosed on pathology in a multicentre cohort, were divided into training and validation sets, internal and external test sets. The regions of interest of the breast lesions were outlined manually by a senior radiologist. We adopted three conventional convolutional neural networks (CNNs), namely, DenseNet 121, Xception, and ResNet 50, as the backbone architectures and incorporated the convolutional block attention module (CBAM) into them for classification. The performance of the models was analysed in terms of the receiver operating characteristic (ROC) curve, accuracy, the positive predictive value (PPV), the negative predictive value (NPV), the F1 score, the precision recall curve (PRC), and heat maps. The final models were compared with the diagnostic performance of conventional CNNs, radiomics models, and two radiologists with specialised breast imaging experience. RESULTS: The best-performing deep learning model, that is, the CBAM-based Xception, achieved an area under the ROC curve (AUC) of 0.970, a sensitivity of 0.848, a specificity of 1.000, and an accuracy of 0.891 on the external test set, which was higher than those of other CNNs, radiomics models, and radiologists. The PRC and the heat maps also indicated the favourable predictive performance of the attention-based CNN model. The diagnostic performance of two radiologists improved with deep learning assistance. CONCLUSIONS: Using an attention-based deep learning model based on CESM images can help to distinguishing benign from malignant breast lesions, and the diagnostic performance of radiologists improved with deep learning assistance.

α-Mangostin Exhibits a Therapeutic Effect on Spinal Cystic Echinococcosis by Affecting Glutamine Metabolism.

Spinal cystic echinococcosis, a severely neglected, rare disease, is characterized by high morbidity, disability, and mortality in prevalent regions. Due to the high-risk nature of surgical treatment and the ineffectiveness of conventional drugs, there is an unmet need for novel safe and effective drugs for the treatment of this disease. In this study, we examined the therapeutic effects of α-mangostin for spinal cystic echinococcosis, and explored its potential pharmacological mechanism. The repurposed drug exhibited a potent in vitro protoscolicidal effect and significantly inhibited the evolution of larval encystation. Moreover, it demonstrated a remarkable anti-spinal cystic echinococcosis effect in gerbil models. Mechanistically, we found that α-mangostin intervention led to intracellular depolarization of mitochondrial membrane potential and reactive oxygen species generation. In addition, we observed elevated expression of autophagic proteins, aggregation of autophagic lysosomes, activated autophagic flux, and disrupted larval microstructure in protoscoleces. Further metabolite profiling showed that glutamine was imperative for autophagic activation and anti-echinococcal effects mediated by α-mangostin. These results suggest that α-mangostin is a potentially valuable therapeutic option against spinal cystic echinococcosis through its effect on glutamine metabolism.

Attention-based Deep Learning for the Preoperative Differentiation of Axillary Lymph Node Metastasis in Breast Cancer on DCE-MRI.

BACKGROUND: Previous studies have explored the potential on radiomics features of primary breast cancer tumor to identify axillary lymph node (ALN) metastasis. However, the value of deep learning (DL) to identify ALN metastasis remains unclear. PURPOSE: To investigate the potential of the proposed attention-based DL model for the preoperative differentiation of ALN metastasis in breast cancer on dynamic contrast-enhanced MRI (DCE-MRI). STUDY TYPE: Retrospective. POPULATION: A total of 941 breast cancer patients who underwent DCE-MRI before surgery were included in the training (742 patients), internal test (83 patients), and external test (116 patients) cohorts. FIELD STRENGTH/SEQUENCE: A 3.0 T MR scanner, DCE-MRI sequence. ASSESSMENT: A DL model containing a 3D deep residual network (ResNet) architecture and a convolutional block attention module, named RCNet, was proposed for ALN metastasis identification. Three RCNet models were established based on the tumor, ALN, and combined tumor-ALN regions on the images. The performance of these models was compared with ResNet models, radiomics models, the Memorial Sloan-Kettering Cancer Center (MSKCC) model, and three radiologists (W.L., H.S., and F. L.). STATISTICAL TESTS: Dice similarity coefficient for breast tumor and ALN segmentation. Accuracy, sensitivity, specificity, intercorrelation and intracorrelation coefficients, area under the curve (AUC), and Delong test for ALN classification. RESULTS: The optimal RCNet model, that is, RCNet-tumor+ALN , achieved an AUC of 0.907, an accuracy of 0.831, a sensitivity of 0.824, and a specificity of 0.837 in the internal test cohort, as well as an AUC of 0.852, an accuracy of 0.828, a sensitivity of 0.792, and a specificity of 0.853 in the external test cohort. Additionally, with the assistance of RCNet-tumor+ALN , the radiologists' performance was improved (external test cohort, P < 0.05). DATA CONCLUSION: DCE-MRI-based RCNet model could provide a noninvasive auxiliary tool to identify ALN metastasis preoperatively in breast cancer, which may assist radiologists in conducting more accurate evaluation of ALN status. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

IRF2BPL gene variants with dystonia: one new Chinese case report.

BACKGROUND: The carriers of damaging heterozygous variants in interferon regulatory factor 2 binding protein-like (IRF2BPL), encoding a member of the IRF2BP family of transcriptional regulators, may be affected by a variety of neurological symptoms, such as neurodevelopmental regression, language and motor developmental delay, seizures, progressive ataxia and a lack of coordination, and even dystonia. CASE PRESENTATION: We report a Chinese boy who presented with dystonia, dysarthria, and normal development due to nonsense IRF2BPL mutation, with intact imaging and EEG findings but without developmental delays or seizures. Whole-exome sequencing revealed a novel nonsense variant IRF2BPL (NM_024496) Exon C.562C > T (p.Arg188*). CONCLUSION: This case report presents a Chinese boy with a novel nonsense variant in IRF2BPL, displaying rapid progressive dystonia and dysarthria, without early developmental delay or epilepsy; expands the IRF2BPL phenotypes in the Chinese population; and raises awareness of patients with IRF2BPL.