Exertional heat stroke with pronounced presentation of microangiopathic hemolytic anemia: A case report.

BACKGROUND: Exertional heat stroke (EHS) is a critical condition arising from prolonged physical exertion in high temperatures that typically presents with normal hemoglobin levels. However, atypical presentations can also occur, leading to significant complications such as hemolytic anemia and organ dysfunction. CASE SUMMARY: This case report describes a male patient who experienced moderate-to-severe anemia that was difficult to correct, with a confirmed diagnosis of microangiopathic hemolytic anemia accompanying multiple organ dysfunction syndrome, indicative of critical EHS. Despite intensive resuscitation efforts, the patient's condition deteriorated, necessitating admission to the intensive care unit for advanced management. CONCLUSION: This case highlights the importance of recognizing atypical presentations of EHS, particularly that with significant hemolytic anemia and concurrent organ failure. Clinicians should maintain a high level of suspicion for these complications in patients displaying symptoms of heat-related illness, especially when caused by strenuous activity, as early diagnosis and intervention are crucial to improve patient outcomes.

Free-Weight Resistance Training Enhances Core Muscle Strength but Does Not Translate to Improved Athletic Performance in Adolescent Canoe/Kayak Athletes.

BACKGROUND/OBJECTIVES: While previous evidence has shown that using free weights for resistance training is a more practical approach to enhancing strength, there is a relatively low prevalence of free-weight resistance training among adolescent kayak/canoe athletes. Therefore, this study aims to assess the impact of free-weight resistance training on body composition and various performance factors among adolescent canoe/kayak athletes. METHODS: Twenty-seven young sprint kayakers and canoeists (14 ± 1 years; 164 ± 7 cm; 56 ± 8 kg) completed this study. Following baseline assessments, athletes were randomly divided into two training groups: the free-weight resistance training group (FW) or the control group (C). The FW group underwent free-weight resistance training sessions twice weekly for 24 weeks. The C group maintained their regular bodyweight training sessions during the same timeframe. All participants performed both the pre- and post-training assessments for the following dependent variables: body composition, upper-body power, upper-body isometric muscle strength, isometric mid-thigh pull, core strength, countermovement jump, balance, anaerobic ability, and aerobic performance. RESULTS: After 24 weeks of training, the free-weight resistance training group exhibited a significant increase in body weight (from 56 ± 5 kg to 58 ± 4 kg, p < 0.05) and improvements in the number of straight leg raise repetitions (from 23 ± 6 to 26 ± 4, p < 0.05) compared to the control group. However, the two groups observed no significant differences between upper-body isometric muscle strength, power, balance, and anaerobic/aerobic performance. CONCLUSIONS: A 24-week training duration might be insufficient for novice participants in resistance training. Future research should consider incorporating an adaptation period or a learning phase for movements before training, thereby enhancing the efficacy of free-weight resistance training in increasing strength.

Clinical and hematological analysis of testicular torsion in children.

Purpose: Analyze the clinical manifestations, laboratory tests, and imaging data of testicular torsion to provide clinical insights for timely and accurate diagnosis and treatment of testicular torsion. Methods: A retrospective analysis was conducted on the clinical data of 67 pediatric patients suspected of testicular torsion, admitted and subjected to surgical exploration from June 2018 to June 2023. Based on whether the torsed testicle was excised during surgery, the patients were divided into orchiectomy group (40 cases) and orchidopexy group (27 cases). Combining clinical symptoms, signs, ultrasound examinations, and laboratory tests, the study aimed to summarize the influencing factors on the onset, diagnosis, and treatment of testicular torsion. Results: The clinical manifestations of all 67 pediatric patients were generally typical. Color Doppler Flow Imaging (CDFI) and surgical exploration were performed for all cases, and the results were consistent. Testicular color doppler ultrasound suggested reduced or absent blood flow, leading to surgical treatment in all cases. All patients had unilateral testicular torsion, with 46 cases (68.66%) on the left side and 21 cases (31.34%) on the right side. Intrafunicular torsion occurred in 60 cases (89.55%), while extrafunicular torsion occurred in 7 cases (10.45%). The onset distribution was as follows: 20 cases in spring, 16 cases in summer, 16 cases in autumn, and 15 cases in winter. Univariate analysis indicated significant statistical differences in age, degree of testicular torsion, duration of symptoms, NEUT, NLR, and occurrence of tunica fluid between the two groups of patients. Multivariate logistic regression analysis showed that the duration of symptoms and the occurrence of hydrocele were independent risk factors for determining testicular viability. Conclusion: Testicular torsion is more common in children and adolescents, with clinical manifestations including scrotal pain, scrotal redness and swelling, abdominal pain, nausea, and vomiting. In the early stages of testicular torsion, inflammatory markers in the blood increase, and preoperative ultrasound indicates hydrocele. This suggests that the testicle is in an early twisted state, with good viability and potential for preservation.

Integrating clinical and biochemical markers: a novel nomogram for predicting lacunes in cerebral small vessel disease.

Background: Lacunes, a characteristic feature of cerebral small vessel disease (CSVD), are critical public health concerns, especially in the aging population. Traditional neuroimaging techniques often fall short in early lacune detection, prompting the need for more precise predictive models. Methods: In this retrospective study, 587 patients from the Neurology Department of the Affiliated Hospital of Hebei University who underwent cranial MRI were assessed. A nomogram for predicting lacune incidence was developed using LASSO regression and binary logistic regression analysis for variable selection. The nomogram's performance was quantitatively assessed using AUC-ROC, calibration plots, and decision curve analysis (DCA) in both training (n = 412) and testing (n = 175) cohorts. Results: Independent predictors identified included age, gender, history of stroke, carotid atherosclerosis, hypertension, creatinine, and homocysteine levels. The nomogram showed an AUC-ROC of 0.814 (95% CI: 0.791-0.870) for the training set and 0.805 (95% CI: 0.782-0.843) for the testing set. Calibration and DCA corroborated the model's clinical value. Conclusion: This study introduces a clinically useful nomogram, derived from binary logistic regression, that significantly enhances the prediction of lacunes in patients undergoing brain MRI for various indications, potentially advancing early diagnosis and intervention. While promising, its retrospective design and single-center context are limitations that warrant further research, including multi-center validation.

Effect of Cardiac Rehabilitation on Cardiorespiratory Fitness in Patients With Acute Myocardial Infarction: Role of Diabetes Mellitus and Glycated Hemoglobin Level.

PURPOSE: Following acute myocardial infarction (AMI), patients with diabetes mellitus (DM) have a poorer prognosis than those without DM. This study aimed to investigate the benefit of cardiac rehabilitation on cardiorespiratory fitness in patients with AMI, examining whether this effect varied depending on DM and glycated hemoglobin (HbA1c) levels. METHODS: Data were collected from the medical records of 324 patients diagnosed with AMI who were subsequently referred to participate in a supervised exercise-based cardiac rehabilitation program. Cardiorespiratory fitness was assessed using cardiopulmonary exercise testing before and at 3 and 6 mo after the start of cardiac rehabilitation. Linear mixed models were used to evaluate changes in cardiorespiratory fitness between patients with and without DM during the follow-up period. RESULTS: In total, 106 patients (33%) had DM. Both patients with and without DM showed a significant improvement in cardiorespiratory fitness from baseline to the 6-mo follow-up. However, the improvement was significantly lower in patients with DM than in those without DM (1.9 ± 1.5 vs. 3.7 ± 3.2 mL/kg/min, P < .001). Among patients with DM, those with HbA1c levels < 7% showed a greater improvement in cardiorespiratory fitness than those with HbA1c ≥ 7% (2.7 ± 1.5 vs. 1.1 ± 1.8 mL/kg/min, P < .001) during the follow-up period. CONCLUSIONS: Improvements in cardiorespiratory fitness following cardiac rehabilitation were significantly lower in patients with AMI and DM. The response to cardiac rehabilitation in patients is influenced by HbA1c levels. These findings suggest potential implications for individualizing cardiac rehabilitation programming and ensuring optimal glycemic control in patients with AMI and DM.

High-quality reference genome of cowpea beetle Callosobruchus maculatus.

Callosobruchus maculatus is one of the most competitive stored grain pests, which causes a great loss to agricultural economy. However, due to an inadequacy of high-quality reference genome, the molecular mechanisms for olfactory and hypoxic adaptations to stored environments are unknown and require to be revealed urgently, which will contribute to the detection and prevention of the invasive pests C. maculatus. Here, we presented a high-quality chromosome-level genome of C. maculatus based on Illumina, Nanopore and Hi-C sequencing data. The total size was 1.2 Gb, and 65.17% (797.47 Mb) of it was identified to be repeat sequences. Among assembled chromosomes, chromosome 10 was considered the X chromosome according to the evidence of reads coverage and homologous genes among species. The current version of high-quality genome provides preferable data resources for the adaptive evolution research of C. maculatus.

Unraveling the Predictors of Enlarged Perivascular Spaces: A Comprehensive Logistic Regression Approach in Cerebral Small Vessel Disease.

Background: This study addresses the predictive modeling of Enlarged Perivascular Spaces (EPVS) in neuroradiology and neurology, focusing on their impact on Cerebral Small Vessel Disease (CSVD) and neurodegenerative disorders. Methods: A retrospective analysis was conducted on 587 neurology inpatients, utilizing LASSO regression for variable selection and logistic regression for model development. The study included comprehensive demographic, medical history, and laboratory data analyses. Results: The model identified key predictors of EPVS, including Age, Hypertension, Stroke, Lipoprotein a, Platelet Large Cell Ratio, Uric Acid, and Albumin to Globulin Ratio. The predictive nomogram demonstrated strong efficacy in EPVS risk assessment, validated through ROC curve analysis, calibration plots, and Decision Curve Analysis. Conclusion: The study presents a novel, robust EPVS predictive model, providing deeper insights into EPVS mechanisms and risk factors. It underscores the potential for early diagnosis and improved management strategies in neuro-radiology and neurology, highlighting the need for future research in diverse populations and longitudinal settings.

High expression levels of centromere protein O participates in cell proliferation of human ovarian cancer.

Ovarian cancer is a common malignant tumor in women, with a high mortality rate ranking first among gynecological tumors. Currently, there is insufficient understanding of the causes, pathogenesis, recurrence and metastasis of ovarian cancer, and early diagnosis and treatment still face great challenges. The sensitivity and specificity of existing ovarian cancer screening methods are still unsatisfactory. Centromere protein O (CENP-O) is a recently discovered structural centromere protein that is involved in cell death and is essential for spindle assembly, chromosome separation, and checkpoint signaling during mitosis. The abnormal high expression of CENP-O was detected in various tumors such as bladder cancer and gastric cancer, and it participates in the regulation of tumor cell proliferation. In this study, we detect the expression abundance of CENP-O mRNA in different ovarian cancer cells ( ES-2, A2780, Caov-3, OVCAR-3 and SK-OV-3). The biological function changes of cell proliferation and apoptosis were detected and the role of CENP-O in ovarian cancer cell proliferation and apoptosis was explored by knocking down the expression of CENP-O gene. The results showed that CENP-O gene was significantly expressed in 5 types of ovarian cancer cell lines. After knocking down the CENP-O gene, the proliferation and cloning ability of ovarian cancer cells decreased, and the apoptosis increased. This study indicates that CENP-O has the potential to be a molecular therapeutic target, and downregulating the expression of CENP-O gene can break the unlimited proliferation ability of cancer cells and promote their apoptosis, providing a foundation and new ideas for subsequent molecular mechanism research and targeted therapy.

Therapeutic potential of cannabidiol (CBD) in anxiety disorders: A systematic review and meta-analysis.

Cannabidiol (CBD), as one of the phytocannabinoids, has a wide range of therapeutic properties for various neuropsychiatric disorders due to central nervous system effects. These therapeutic properties demonstrated by preclinical and clinical studies encompass more than just anticonvulsant, anti-arthritic, analgesic, anti-inflammatory, antioxidant, antitumor, antiemetic, antipsychotic and neuroprotective effects. It has been hypothesized that CBD holds potential in the treatment of various neuropsychiatric and anxiety disorders. Thus, PRISMA was used as a guide for our systematic review. Eight of the 1550 articles screened in June 2023 were eligible for meta-analysis. Based on the 316 participants included in these eight articles, this meta-analysis revealed a substantial significant impact of CBD on anxiety with a considerable effect size (Hedges' g = -0.92, 95% CI -1.80 to -0.04). In addition, this meta-analysis focuses on the efficacy of CBD in treating anxiety disorders such as generalized anxiety disorder (GAD), social anxiety disorder (SAD), and post-traumatic stress disorder (PTSD). However, caution should be exercised in interpreting our findings due to the limited size of the clinical sample, and additional trials ought to be carried out if deemed necessary.

SMARCA5 reprograms AKR1B1-mediated fructose metabolism to control leukemogenesis.

A significant variation in chromatin accessibility is an epigenetic feature of leukemia. The cause of this variation in leukemia, however, remains elusive. Here, we identify SMARCA5, a core ATPase of the imitation switch (ISWI) chromatin remodeling complex, as being responsible for aberrant chromatin accessibility in leukemia cells. We find that SMARCA5 is required to maintain aberrant chromatin accessibility for leukemogenesis and then promotes transcriptional activation of AKR1B1, an aldo/keto reductase, by recruiting transcription co-activator DDX5 and transcription factor SP1. Higher levels of AKR1B1 are associated with a poor prognosis in leukemia patients and promote leukemogenesis by reprogramming fructose metabolism. Moreover, pharmacological inhibition of AKR1B1 has been shown to have significant therapeutic effects in leukemia mice and leukemia patient cells. Thus, our findings link the aberrant chromatin state mediated by SMARCA5 to AKR1B1-mediated endogenous fructose metabolism reprogramming and shed light on the essential role of AKR1B1 in leukemogenesis, which may provide therapeutic strategies for leukemia.

Risk factors of non-arteritic anterior ischaemic optic neuropathy and central retinal artery occlusion.

AIM: To investigate the difference in risk factors between non-arteritic anterior ischaemic optic neuropathy (NAION) and central retinal artery occlusion (CRAO) and develop a predictive diagnostic nomogram. METHODS: The study included 37 patients with monocular NAION, 20 with monocular CRAO, and 24 with hypertension. Gender, age, and systemic diseases were recorded. Blood routine, lipids, hemorheology, carotid and brachial artery doppler ultrasound, and echocardiography were collected. The optic disc area, cup area, and cup-to-disc ratio (C/D) of the unaffected eye in the NAION and CRAO group and the right eye in the hypertension group were measured. RESULTS: The carotid artery intimal medial thickness (C-IMT) of the affected side of the CRAO group was thicker (P=0.039) and its flow-mediated dilation (FMD) was lower (P=0.049) than the NAION group. Compared with hypertension patients, NAION patients had higher whole blood reduced viscosity low-shear (WBRV-L) and erythrocyte aggregation index (EAI; P=0.045, 0.037), and CRAO patients had higher index of rigidity of erythrocyte (IR) and erythrocyte deformation index (EDI; P=0.004, 0.001). The optic cup and the C/D of the NAION group were smaller than the other two groups (P<0.0001). The diagnostic prediction model showed high diagnostic specificity (83.7%) and sensitivity (85.6%), which was highly related to hypertension, the C-IMT of the affected side, FMD, platelet (PLT), EAI, and C/D. CONCLUSION: CRAO patients show thicker C-IMT and worse endothelial function than NAION. NAION and CRAO may be related to abnormal hemorheology. A small cup and small C/D may be involved in NAION. The diagnostic nomogram can be used to preliminarily identify NAION and CRAO.

Carbonization of quercetin into nanogels: a leap in anticoagulant development.

Quercetin, a flavonoid abundantly found in onions, fruits, and vegetables, is recognized for its pharmacological potential, especially for its anticoagulant properties that work by inhibiting thrombin and coagulation factor Xa. However, its clinical application is limited due to poor water solubility and bioavailability. To address these limitations, we engineered carbonized nanogels derived from quercetin (CNGsQur) using controlled pyrolysis and polymerization techniques. This led to substantial improvements in its anticoagulation efficacy, water solubility, and biocompatibility. We generated a range of CNGsQur by subjecting quercetin to varying pyrolytic temperatures and then assessed their anticoagulation capacities both in vitro and in vivo. Coagulation metrics, including thrombin clotting time (TCT), activated partial thromboplastin time (aPTT), and prothrombin time (PT), along with a rat tail bleeding assay, were utilized to gauge the efficacy. CNGsQur showed a pronounced extension of coagulation time compared to uncarbonized quercetin. Specifically, CNGsQur synthesized at 270 °C (CNGsQur270) exhibited the most significant enhancement in TCT, with a binding affinity to thrombin exceeding 400 times that of quercetin. Moreover, variants synthesized at 310 °C (CNGsQur310) and 290 °C (CNGsQur290) showed the most substantial delays in PT and aPTT, respectively. Our findings indicate that the degree of carbonization significantly influences the transformation of quercetin into various CNGsQur forms, each affecting distinct coagulation pathways. Additionally, both intravenous and oral administrations of CNGsQur were found to extend rat tail bleeding times by up to fivefold. Our studies also demonstrate that CNGsQur270 effectively delays and even prevents FeCl3-induced vascular occlusion in a dose-dependent manner in mice. Thus, controlled pyrolysis offers an innovative approach for generating quercetin-derived CNGs with enhanced anticoagulation properties and water solubility, revealing the potential for synthesizing self-functional carbonized nanomaterials from other flavonoids for diverse biomedical applications.

Overexpression of GPX2 gene regulates the development of porcine preadipocytes and skeletal muscle cells through MAPK signaling pathway.

Glutathione peroxidase 2 (GPX2) is a selenium-dependent enzyme and protects cells against oxidative damage. Recently, GPX2 has been identified as a candidate gene for backfat and feed efficiency in pigs. However, it is unclear whether GPX2 regulates the development of porcine preadipocytes and skeletal muscle cells. In this study, adenoviral gene transfer was used to overexpress GPX2. Our findings suggest that overexpression of GPX2 gene inhibited proliferation of porcine preadipocytes. And the process is accompanied by the reduction of the p-p38. GPX2 inhibited adipogenic differentiation and promoted lipid degradation, while ERK1/2 was reduced and p-p38 was increased. Proliferation of porcine skeletal muscle cells was induced after GPX2 overexpression, was accompanied by activation in JNK, ERK1/2, and p-p38. Overexpression methods confirmed that GPX2 has a promoting function in myoblastic differentiation. ERK1/2 pathway was activated and p38 was suppressed during the process. This study lays a foundation for the functional study of GPX2 and provides theoretical support for promoting subcutaneous fat reduction and muscle growth.

Optimizing early neurological deterioration prediction in acute ischemic stroke patients following intravenous thrombolysis: a LASSO regression model approach.

Background: Acute ischemic stroke (AIS) remains a leading cause of disability and mortality globally among adults. Despite Intravenous Thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA) emerging as the standard treatment for AIS, approximately 6-40% of patients undergoing IVT experience Early Neurological Deterioration (END), significantly impacting treatment efficacy and patient prognosis. Objective: This study aimed to develop and validate a predictive model for END in AIS patients post rt-PA administration using the Least Absolute Shrinkage and Selection Operator (LASSO) regression approach. Methods: In this retrospective cohort study, data from 531 AIS patients treated with intravenous alteplase across two hospitals were analyzed. LASSO regression was employed to identify significant predictors of END, leading to the construction of a multivariate predictive model. Results: Six key predictors significantly associated with END were identified through LASSO regression analysis: previous stroke history, Body Mass Index (BMI), age, Onset to Treatment Time (OTT), lymphocyte count, and glucose levels. A predictive nomogram incorporating these factors was developed, effectively estimating the probability of END post-IVT. The model demonstrated robust predictive performance, with an Area Under the Curve (AUC) of 0.867 in the training set and 0.880 in the validation set. Conclusion: The LASSO regression-based predictive model accurately identifies critical risk factors leading to END in AIS patients following IVT. This model facilitates timely identification of high-risk patients by clinicians, enabling more personalized treatment strategies and optimizing patient management and outcomes.

Electrode-Supported Endohedral Metallofullerenes: Insights into the Confined Internal Dynamics.

Endohedral metallofullerenes show great promise as molecular-scale memory units due to their robust architecture and protective capability for encapsulated atoms. However, the flat potential-energy surface within the cage often results in a severe disorder of encapsulated atoms. Here, we focused on prototypical systems involving Li@C60 on metallic surfaces, emphasizing the electrode's confinement effect on caged dynamics. We demonstrated that the varying interfacial stabilities induced by Li motion predominantly depend on the synergetic effect of van der Waals forces and covalent bonds rather than the previously assumed electrostatic interactions. We unveiled that the repulsion effect between encapsulated atom and the metal electrode primarily arises from the antibonding states between the metal states below the Fermi level and the degenerated frontier orbitals from HOMO-4 to HOMO. By manipulating orbital interactions, we observed an ordered arrangement of the encapsulated atom on Rec-Pt(111) at room temperature. Furthermore, our findings underscore the disruptive influence of electric fields on the stability of distinct Li positions, a phenomenon closely tied to the dipole moment induced by Li motion. This research provides a new perspective on the confined internal dynamics of endohedral metallofullerenes by manipulating cage-electrode interactions, contributing to precisely controlled molecular electronics.

Development of an NLR-ID Toolkit and Identification of Novel Disease-Resistance Genes in Soybean.

The recognition of pathogen effectors through the nucleotide-binding leucine-rich repeat receptor (NLR) family is an important component of plant immunity. In addition to typical domains such as TIR, CC, NBS, and LRR, NLR proteins also contain some atypical integrated domains (IDs), the roles of which are rarely investigated. Here, we carefully screened the soybean (Glycine max) genome and identified the IDs that appeared in the soybean TNL-like proteins. Our results show that multiple IDs (36) are widely present in soybean TNL-like proteins. A total of 27 Gm-TNL-ID genes (soybean TNL-like gene encoding ID) were cloned and their antiviral activity towards the soybean mosaic virus (SMV)/tobacco mosaic virus (TMV) was verified. Two resistance (R) genes, SRA2 (SMV resistance gene contains AAA_22 domain) and SRZ4 (SMV resistance gene contains zf-RVT domain), were identified to possess broad-spectrum resistance characteristics towards six viruses including SMV, TMV, plum pox virus (PPV), cabbage leaf curl virus (CaLCuV), barley stripe mosaic virus (BSMV), and tobacco rattle virus (TRV). The effects of Gm-TNL-IDX (the domain of the Gm-TNL-ID gene after the TN domain) on the antiviral activity of a R protein SRC7TN (we previously reported the TN domain of the soybean broad-spectrum resistance gene SRC7) were validated, and most of Gm-TNL-IDX inhibits antiviral activity mediated by SRC7TN, possibly through intramolecular interactions. Yeast-two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays showed that seven Gm-TNL-IDX interacted with SMV-component proteins. Truncation analysis on a broad-spectrum antiviral protein SRZ4 indicated that SRZ4TIR is sufficient to mediate antiviral activity against SMV. Soybean cDNA library screening on SRZ4 identified 48 interacting proteins. In summary, our results indicate that the integration of IDs in soybean is widespread and frequent. The NLR-ID toolkit we provide is expected to be valuable for elucidating the functions of atypical NLR proteins in the plant immune system and lay the foundation for the development of engineering NLR for plant-disease control in the future.

3 M antimicrobial incise drape combined with MEBO in wound recovery of postoperative hypospadias surgery.

OBJECTIVE: To evaluate the efficacy of different dressing methods in wound healing and the postoperative outcome in children who underwent hypospadias repair. METHODS: Altogether 109 children with distal hypospadias who underwent urethroplasty were recruited from our hospital between January 2021 and March 2023. All patients were randomized in two groups according to the different dressing methods: Group A receiving 3 M antimicrobial incise drape + MEBO (moisture-exposed burn ointment) and Group B receiving absorbent dressing + elastic bandage dressing. The age at surgery, operation time, bleeding during the dressing, postoperative changes in glans color, dressing fell off, comfort of children during the dressing, difficulty in dressing removal, and degree of pain during dressing removal were compared between the two groups. RESULTS: Differences in age at surgery (p = 0.337) and operation time (p = 0.055) were not significant between the two groups. The overall effectiveness of the dressing was better in Group A than that in Group B. Only five cases in Group A had blood leakage after dressing (p = 0.006), and there was no dressing dislocation (p < 0.001) or glans color abnormality (p < 0.001). Moreover, the number of complication cases was less. The overall comfort and pain degree during dressing removal in Group A was better than that in Group B (p < 0.001). CONCLUSION: Postoperative dressing using 3 M antimicrobial incise drape + MEBO can achieve lower incidence rates of bleeding during dressing, postoperative glans darkening, and dressing falling off, a lower pain degree during dressing removal, and a better overall comfort level than those of the control group. This method is cost-effective and clinically safe, which contributes to the postoperative recovery of children with hypospadias and is thus worth promoting and applying.

Development and multi-institutional validation of a deep learning model for grading of vesicoureteral reflux on voiding cystourethrogram: a retrospective multicenter study.

Background: Voiding cystourethrography (VCUG) is the gold standard for the diagnosis and grading of vesicoureteral reflux (VUR). However, VUR grading from voiding cystourethrograms is highly subjective with low reliability. This study aimed to develop a deep learning model to improve reliability for VUR grading on VCUG and compare its performance to that of clinicians. Methods: In this retrospective study in China, VCUG images were collected between January 2019 and September 2022 from our institution as an internal dataset for training and 4 external data sets as external testing set for validation. Samples were divided into training (N = 1000) and validation sets (N = 500), internal testing set (N = 168), and external testing set (N = 280). An ensemble learning-based model, Deep-VCUG, using Res-Net 101 and the voting methods was developed to predict VUR grade. The grading performance was assessed using heatmaps, area under the receiver operating characteristic curve (AUC), sensitivity, specificity, accuracy, and F1 score in the internal and external testing set. The performances of four clinicians (2 pediatric urologists and 2 radiologists) with and without the Deep-VCUG assisted to predict VUR grade were explored in external testing sets. Findings: A total of 1948 VCUG images were collected (Internal dataset = 1668; multi-center external dataset = 280). For assessing unilateral VUR grading, the Deep-VCUG achieved AUCs of 0.962 (95% confidence interval [CI]: 0.943-0.978) and 0.944 (95% [CI]: 0.921-0.964) in the internal and external testing sets, respectively, for bilateral VUR grading, the Deep-VCUG also achieved high AUCs of 0.960 (95% [CI]: 0.922-0.983) and 0.924 (95% [CI]: 0.887-0.957). The Deep-VCUG model using voting method outperformed single model and clinician in terms of classification based on VCUG image. Moreover, Under the Dee-VCUG assisted, the classification ability of junior and senior clinicians was significantly improved. Interpretation: The Deep-VCUG model is a generalizable, objective, and accurate tool for vesicoureteral reflux grading based on VCUG imaging and had good assistance with clinicians to VUR grading applicability. Funding: This study was supported by Natural Science Foundation of China, "Fuqing Scholar" Student Scientific Research Program of Shanghai Medical College, Fudan University, and the Program of Greater Bay Area Institute of Precision Medicine (Guangzhou).

The induction of SHP-1 degradation by TAOK3 ensures the responsiveness of T cells to TCR stimulation.

Thousand-and-one-amino acid kinase 3 (TAOK3) is a serine and threonine kinase that belongs to the STE-20 family of kinases. Its absence reduces T cell receptor (TCR) signaling and increases the interaction of the tyrosine phosphatase SHP-1, a major negative regulator of proximal TCR signaling, with the kinase LCK, a component of the core TCR signaling complex. Here, we used mouse models and human cell lines to investigate the mechanism by which TAOK3 limits the interaction of SHP-1 with LCK. The loss of TAOK3 decreased the survival of naïve CD4+ T cells by dampening the transmission of tonic and ligand-dependent TCR signaling. In mouse T cells, Taok3 promoted the secretion of interleukin-2 (IL-2) in response to TCR activation in a manner that depended on Taok3 gene dosage and on Taok3 kinase activity. TCR desensitization in Taok3-/- T cells was caused by an increased abundance of Shp-1, and pharmacological inhibition of Shp-1 rescued the activation potential of these T cells. TAOK3 phosphorylated threonine-394 in the phosphatase domain of SHP-1, which promoted its ubiquitylation and proteasomal degradation. The loss of TAOK3 had no effect on the abundance of SHP-2, which lacks a residue corresponding to SHP-1 threonine-394. Modulation of SHP-1 abundance by TAOK3 thus serves as a rheostat for TCR signaling and determines the activation threshold of T lymphocytes.