Objectives:Sturge-Weber Syndrome (SWS) is a rare neurocutaneous disorder requiring early and accurate diagnosis. This study aims to develop a deep learning framework for automatic diagnosis of SWS by detecting leptomeningeal angiomatosis (LA) in brain magnetic resonance images (MRI). Methods:This retrospective study includes 40 SWS patients and 101 healthy controls. T1-weighted MRI were collected over 15 years with different scanners. Multi-scale harmonization was proposed to normalize the images to uniform mean and standard deviation. We developed a deep learning model based on the UNet framework with convolutional neural networks and transformer. A multi-task pipeline was designed to perform LA segmentation and SWS classification. The model was pre-trained on a public dataset and fine-tuned and tested on our dataset using a 5-fold cross validation. The segmentation and classification results were compared with the ground truth and human readers using various metrics at the voxel and LA level. Results:For LA segmentation, our model achieved overall Dice, voxel-level sensitivity, specificity, accuracy, and kappa of 0.768, 0.772, 0.992, 0.983, and 0.760, respectively. The LA volume segmented by our model showed a high agreement and consistency with the ground truth, outperforming the human readers. For SWS classification, our model achieved sensitivity, specificity, accuracy, and AUC of 0.974, 1.000, 0.993, and 0.998, respectively. Conclusion:We developed a multi-task learning framework for automated LA segmentation and SWS classification. This single-center proof-of-concept study shows promising performance in both tasks. External validation may boost the clinical application of the developed model, assisting less-experienced neurologists for improved SWS diagnosis.

Background:Craniosynostosis complicated with hydrocephalus is a rare pediatric condition with complex and debated treatment protocols. The optimal sequence and combination of surgical interventions remain controversial, particularly in cases where both conditions coexist. Understanding effective management strategies is crucial to improving outcomes in these patients. Case Description:We analyzed nine pediatric patients treated at our institution for combined craniosynostosis and hydrocephalus. The cohort included seven males and two females, aged 8 to 45 months. Seven patients had syndromic craniosynostosis, while two had non-syndromic forms. All were admitted due to abnormal facial features. At admission, six had normal head circumference, two had reduced, and one had increased head circumference. Elevated intracranial pressure was observed in eight patients. All underwent cranioplasty, with cerebrospinal fluid leakage occurring in two cases. Five patients required ventriculoperitoneal (VP) shunt placement due to persistent hydrocephalus after surgery. Follow-up, averaging 53.6 months, showed improved cranial shape and symptom relief in eight patients, and resolution or significant mitigation of hydrocephalus in all cases. Conclusions:Craniosynostosis frequently coexists with hydrocephalus, particularly in syndromic cases with normal head circumference. Based on our institutional experience, initial cranioplasty was commonly performed to address cranial deformities and was associated with improvement in some patients. However, persistent hydrocephalus in certain cases required additional intervention, such as VP shunting.

Currarino syndrome (CS) is a congenital disorder caused by MNX1 gene mutation, resulting in abnormal caudal cell mass development. Clinical presentation varies from severe to mild forms. Classic triad of CS includes sacral agenesis, presacral mass, and anorectal malformation (ARM). We report a pair of monozygotic twins, both with the MNX1: c.780C>G mutation, presenting with different clinical phenotypes of Currarino syndrome (CS). Both were suspected of anorectal atresia in utero, and postnatal diagnosis confirmed CS with tethered cord syndrome (TCS). They underwent staged surgeries, with normal growth at 10 months follow-up. Additionally, a retrospective analysis of 95 CS cases diagnosed between April 2010 and April 2024 at Shanghai Xinhua Hospital was performed. Clinical, imaging, and pathological data were collected, and binary logistic regression was used to analyze the correlation between clinical factors and TCS. A literature review of twin CS cases was also conducted. Of the 95 patients, 23.2% had complete CS, and 76.8% had incomplete CS. TCS was present in 55.8% of cases. Logistic regression showed no significant correlation between age, sex, sacral deformity severity, ARM type, presacral mass, and TCS. Two previous twin CS cases were identified, both with differing phenotypes. CS exhibits phenotypic variability, and monozygotic twins with the same MNX1 mutation may present with different severities. The MNX1: c.780C>G mutation broadens the genetic spectrum of CS. TCS is common, emphasizing the need for multidisciplinary management. Surgical approaches should be personalized based on presentation.

Crouzon syndrome is generally considered to be hereditary. However, a significant proportion of cases involve de novo mutations. It is characterized by premature closure of the cranial sutures, which leads to craniofacial deformities and/or ocular abnormalities. This report details the case of an 8-month-old female patient who was admitted to our hospital with bilateral exophthalmos. Physical examination indicated Crouzon syndrome. A CT scan of the head revealed bilateral closure of the temporal-parietal sutures, as well as multiple indentations on the medial plates of the temporal and occipital bones. Next-generation sequencing (NGS) detected a novel FGFR2 gene mutation (p.Cys342Tyr), which confirmed the diagnosis. Following a comprehensive evaluation, the patient underwent successful cranial suture reconstruction surgery. Postoperatively, the infant was extubated and transferred to the paediatric intensive care unit (PICU). This report emphasizes the importance of Next-generation sequencing (NGS) in the differential diagnosis of Crouzon syndrome by presenting a unique case involving only temporal-parietal suture closure. Furthermore, it highlights the importance of genetic testing for patients with subtle manifestations of Crouzon syndrome, providing clinical answers and guiding management.

Cirrhosis-associated matrix stiffness is a major biophysical driver of hepatocellular carcinoma (HCC). How fibrosis-induced stiffness activates oncogenic YAP signaling remains unclear. We investigated the role of ficolin-3 (FCN3) in stiffness-associated regulation of the O-GlcNAc transferase (OGT)–YAP axis in HCC. Public transcriptomic datasets comparing cirrhotic and normal liver tissues (GSE114564), as well as HCC tissues from patients with and without cirrhosis (GSE14520), were analyzed. FCN3 protein expression was evaluated in 67 paired HCC and adjacent non-tumorous tissues, and a subset of 20 matched cases was further analyzed by quantitative reverse-transcription PCR and atomic force microscopy. Controlled-stiffness substrates, FCN3 gain- and loss-of-function models, and murine H22 allograft and human HepG2 xenograft models were used for functional validation. Mechanistic studies included RNA sequencing, cycloheximide chase assays, subcellular fractionation, co-immunoprecipitation, structural prediction, YAP-S127A rescue, Thiamet-G treatment, and YAP knockdown. FCN3 was downregulated in cirrhotic liver and HCC with cirrhosis. In clinical samples, tumor stiffness inversely correlated with FCN3 expression. FCN3 overexpression curtailed proliferation, clonogenicity, migration, and invasion in vitro and suppressed tumor growth in vivo. Transcriptomics revealed YAP pathway inhibition without changes in upstream kinases. FCN3 did not alter YAP mRNA but reduced YAP protein, increased p-YAP(S127), limited nuclear YAP, and shortened YAP half-life. Co-IP showed FCN3 binds OGT and disrupts OGT–YAP association, decreasing YAP O-GlcNAcylation. YAP knockdown partially attenuated FCN3’s anti-tumor effects. These findings support a stiffness-associated FCN3–OGT–YAP regulatory model in HCC, in which FCN3 expression is associated with reduced OGT–YAP interaction, decreased YAP O-GlcNAcylation, and restricted YAP nuclear activity. Further studies are required to establish direct molecular competition and its independence from canonical Hippo–LATS signaling.

Craniosynostosis, marked by premature fusion of the cranial sutures, leads to abnormal head shapes and possible neurological complications. This report describes a 4-year-and-2-month-old boy diagnosed with pancraniosynostosis who presented with progressive forehead protrusion 11 months after initial cranial suture reconstruction. Whole exome sequencing identified 2 novel compound heterozygous variants in the IL11RA gene (c.673C>T, P . Arg225Trp inherited from the mother and c.728C>G, P . Pro243Arg inherited from the father), both classified as variants of uncertain significance. The patient underwent successful secondary cranial suture reconstruction with favorable 6-month outcomes. These findings expand the mutational spectrum of IL11RA -associated craniosynostosis and highlight the importance of including IL11RA in genetic testing panels for pancraniosynostosis, even in the absence of classic syndromic features.

Abstract Malignant rhabdoid tumors (MRT) are highly aggressive pediatric malignancies driven by SMARCB1 loss and consequent epigenetic dysregulation, with dismal survival rates underscoring the need for novel therapies. Given the central role of chromatin modifiers in MRT pathogenesis, we investigated a novel combinatorial epigenetic approach simultaneously targeting histone deacetylases (HDACs) and bromodomain and extraterminal (BET) family proteins. Using a focused epigenetic compound screen across multiple MRT cell lines, we identified that the HDAC inhibitor panobinostat (LBH589) and the BET inhibitor birabresib (OTX015) act synergistically to inhibit cell proliferation, with combination index (CI) values consistently <1. Transcriptomic profiling revealed that this synergy is underpinned by a profound downregulation of cell cycle genes, leading to G1/S phase arrest. Mechanistically, the combination therapy cooperatively restores the expression of the cyclin-dependent kinase inhibitors p21 and p16. This restoration inhibits cyclin D1–CDK4/6 kinase activity, reduces retinoblastoma protein (Rb) phosphorylation, and consequently represses the E2F1 transcriptional program and its key targets, including cyclin A2 and cyclin B1. In vivo, this dual-epigenetic targeting significantly attenuated tumor growth in MRT xenograft models, outperforming either monotherapy, and was associated with suppressed proliferation and E2F1 signaling. Our findings unveil a novel synergistic strategy that pharmacologically recapitulates a core SMARCB1-mediated tumor-suppressive circuit, nominating combined HDAC and BET inhibition as a promising therapeutic avenue for MRT.

The clinical characteristics and treatment of the rare methylmalonic academia (MMA) with Dandy-Walker syndrome (DWS) are still unclear. This study aims to provide insights into this rare pediatric condition. A retrospective analysis was conducted on MMA cases from our pediatric ICU database (2006–2021), identifying those with concurrent DWS. Onset age, clinical features, genetic types, treatment, and prognosis were analyzed. MMA diagnosis was confirmed via blood and urine tandem mass spectrometry, while DWS was diagnosed through cranial MRI. Follow-up was conducted via phone or outpatient visits. Of 198 MMA cases, four (three males, one female) had DWS, with an average onset age of 38 days (range: 4–60 days). Vomiting (3/4) was the most common symptom. Two patients had a small head circumference. Blood homocysteine levels ranged from 130.8–187.3 µmol/L, and urine MMA levels ranged from 24.5–236.1 mmol/mol·creatinine. Blood C3 and C3/C2 ratios were elevated in all patients. MRI showed cerebellar vermis dysplasia and fourth ventricle cystic dilatation. All patients received treatment with medications and specialized formula. Case 3 developed elevated intracranial pressure (ICP) and died from multi-organ failure. Cases 1, 2, and 4 had ventriculoperitoneal shunt (VPS) for ICP. Case 1 died of respiratory failure 10 months post-surgery, Case 2 from severe pneumonia 96 months post-surgery, and Case 4 remained stable at 32 months follow-up. DWS may present as a clinical manifestation of MMA, often with early onset and severe symptoms. Elevated ICP and hydrocephalus are common, and VPS may effectively alleviate ICP and improve prognosis.

Hip fractures have become a significant clinical concern on a global scale in recent years. The burgeoning aging population has exacerbated this issue, leading to a rise in the number of hip fracture cases coupled with concomitant geriatric ailments. Therefore, it poses a huge challenge to anesthesiologists with the increasing number of critically ill patients who are not suitable for general anesthesia and intrathecal anesthesia. Ultrasound-guided nerve blocks combined with sedation have not previously been documented in critically ill patients. We administered an ultrasound-guided modified iliac fascia block combined with sacral plexus block to an 88-year-old male patient with a left femoral fracture suffering from severe multi-systemic diseases. Concurrently, the patient received intravenous anesthesia via propofol and dexmedetomidine, with monitoring conducted through bispectral index. Subsequently, the surgery was completed smoothly and the patient demonstrated accelerated postoperative recovery without significant discomfort and a successful discharge. This innovative approach significantly contributed to achieving successful surgical anesthesia and postoperative analgesia, thereby facilitating early recovery and discharge from the hospital. We propose that ultrasound-guided nerve blocks with sedation show promise for critically ill patients.

BACKGROUND:Triple-negative breast cancer (TNBC) is an aggressive malignancy with limited therapeutic options. Opioids are commonly used for perioperative and chronic pain management in patients with cancer. Notably, the κ-opioid receptor (KOR) has shown antitumour potential, but its therapeutic impact in TNBC is unknown. METHODS:We analysed KOR expression in TNBC patient cohorts and tissue microarrays. The effects of the KOR agonist U69593 were assessed on key malignant phenotypes in vitro, including apoptosis and mitochondrial integrity. We then validated its impact on tumour growth and metastasis using subcutaneous and haematogenous mouse models. RESULTS:KOR expression was downregulated in TNBC tissue (n=60, P=0.0004), and higher KOR levels were associated with more favourable patient prognosis (n=45 low vs 15 high, P=0.03). The KOR agonist U69593 suppressed TNBC progression both in vitro, by inhibiting cell proliferation, migration, and invasion while inducing apoptosis, and in vivo, by suppressing tumour growth and metastasis. U69593 induced severe mitochondrial damage, evidenced by loss of mitochondrial membrane potential and depleted intracellular adenosine triphosphate. Metabolomic profiling revealed that this was linked to disruption of the urea cycle, leading to the accumulation of toxic ammonia. Restoring urea cycle function by overexpression of the key enzyme ornithine transcarbamylase rescued TNBC cells from U69593-induced apoptosis and abrogated its antitumour effects. CONCLUSIONS:These findings demonstrate that the KOR agonist U69593 restrains TNBC progression by disrupting urea cycle function and compromising mitochondrial integrity, highlighting the potential of dual-action therapeutics that combine effective analgesia with direct antitumour activity.

West syndrome (WS) is a neurodevelopmental disorder causing retardation in many patients. Hypsarrhythmia electroencephalography (EEG) and motor spasms are considered as clinical manifestations of WS. Visual inspection of hypsarrhythmia in long-term EEG recordings is time-consuming and unreliable. This study investigates automated hypsarrhythmia diagnosis using machine learning and dedicated feature selection. The 101 WS patients and 155 healthy controls (HCs) were involved. The 15-s representative hypsarrhythmia and nonhypsarrhythmia EEG segments were selected from each WS patient, and a normal EEG segment with the same length was picked from each HC. Amplitude-, spectrum-, entropy-, and correlation-related features were extracted from each EEG segment. Four popular classifiers, i.e., logistic regression (LR), support vector machine (SVM), adaptive boosting (AdaBoost), and K-nearest neighbors (KNNs), were employed to perform three-label classification among hypsarrhythmia, nonhypsarrhythmia, and HC. Dedicated feature selection was implemented to identify an optimal feature subset for effective classification. Accuracy (ACC), sensitivity (SN), specificity (SP), and the area under the receiver operating characteristic curve (AUC) were adopted as performance metrics. AdaBoost produced the best results in most metrics, i.e., 0.975, 0.971, 0.988, and 0997 for ACC, SN, SP, and AUC, respectively. RMS computed in the delta band and entropy features computed in the beta band were identified as the two most relevant features. Our findings provide useful information for clinical hypsarrhythmia diagnosis and may boost the application of machine learning for automated WS diagnosis in clinical practice.

ABSTRACT Background Stroke is the most significant cause of death and disability around the world. It is the second leading cause of death after cardiovascular disease. Currently, the triglyceride–glucose (TyG) index has proven to be a reliable surrogate indicator of IR in stroke studies. However, the relationship between TyG and poor functional outcomes in patients with ischemic stroke remains unclear. Accordingly, this study aimed to explore the relationship between TyG index and clinical outcomes at 3 months after acute ischemic stroke (AIS). Methods The clinical data of 564 AIS patients admitted to the Second People's Hospital of Hefei from January 2020 to September 2024 were collected. According to the mRS score at 3 months after onset, the patients were divided into a poor functional prognosis group and a good functional prognosis group. Univariate and multivariate logistic regression models were used to explore the correlation between the TyG index at admission and the 3‐month functional prognosis of AIS patients. The receiver operating characteristic (ROC) curve was used to evaluate the predictive ability of the TyG index and the TyG index combined with the admission NIHSS score (TyG‐NIHSS) for the 3‐month functional prognosis of AIS patients. Results A total of 564 AIS patients were included, with 165 cases (29.25%) in the poor functional prognosis group and 399 cases (70.75%) in the good functional prognosis group. Multivariate logistic regression analysis showed that systolic blood pressure at admission, NIHSS score, and TyG index were independent risk factors for poor functional prognosis at 3 months in AIS patients (p < 0.05). The higher the TyG index, the higher the risk of poor functional prognosis at 3 months (OR = 3.18, 95% CI: 2.252–4.499, p < 0.001). ROC curve analysis showed that the area under the curve (AUC) for the TyG index to predict poor functional prognosis at 3 months in AIS patients was 0.650 (95% CI: 0.598–0.702, p < 0.001), with a sensitivity of 61.2% and a specificity of 62.7%. The AUC for TyG‐NIHSS to predict poor functional prognosis at 3 months in AIS patients was 0.836 (95% CI: 0.799–0.873, p < 0.001), with a sensitivity of 80.6% and a specificity of 76.7%. Conclusion The TyG index is an independent but moderate predictor of poor outcomes at 3 months poststroke. However, TyG‐NIHSS represents a highly discriminative multivariate model. This model demonstrates good predictive ability and high predictive accuracy.

This case report presents a 5-year-old boy diagnosed with juvenile hyaline fibromatosis (JHF), an extremely rare autosomal recessive disorder characterized by the abnormal accumulation of collagen. The patient exhibited a recurrent giant subcutaneous tumor measuring 20 cm in diameter, along with multiple tumors in the oral cavity, gingiva, and joints, leading to significant facial deformity and functional impairments. Previous surgeries at ages 1 and 2 for tumor removal resulted in recurrence. Surgical intervention was performed to excise the large tumor and alleviate symptoms. Pathologic analysis confirmed the diagnosis of JHF. This case highlights the challenges in managing JHF and the need for multidisciplinary approaches in treatment.

ObjectivesSturge-Weber syndrome (SWS) is a congenital neurological disorder occurring in the early childhood. Timely diagnosis of SWS is essential for proper medical intervention that prevents the development of various neurological issues. Leptomeningeal angiomas (LA) are the clinical manifestation of SWS. Detection of LA is currently performed by manual inspection of the magnetic resonance images (MRI) by experienced neurologist, which is time-consuming and lack of inter-rater consistency. The aim of the present study is to investigate automated LA detection in MRI of SWS patients.MethodsA Mamba-based encoder-decoder architecture was employed in the present study. Particularly, a multi-scale multi-scan strategy was proposed to convert 3-D volume into 1-D sequence, enabling capturing long-range dependency with reduced computation complexity. Our dataset consists of 40 SWS patients with T1-enhanced MRI. The proposed model was first pre-trained on a public brain tumor segmentation (BraTS) dataset and then fine-tuned and tested on the SWS dataset using 5-fold cross validation.Results and conclusionOur results show excellent performance of the proposed method, e.g., Dice score of 91.53% and 78.67% for BraTS and SWS, respectively, outperforming several state-of-the-art methods as well as two neurologists. Mamba-based deep learning method can automatically identify LA in MRI images, enabling automated SWS diagnosis in clinical settings.

Purpose Atypical teratoid/rhabdoid tumor (AT/RT) is a kind of central nervous system malignant tumor in children. In this study, we aimed to develop a practically clinical nomogram and risk grouping system to predict 1-year overall survival for patients with atypical teratoid/rhabdoid tumor. Methods The nomogram was constructed based on the pediatric tumor registry of Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine. Fifty-four information-integrated patients with atypical teratoid/rhabdoid tumor were included from the database. Cox regression analyses were used to select independent prognostic factors. Based on the fitted multivariate Cox regression model, a nomogram of 1-year overall survival for atypical teratoid/rhabdoid tumor patients was generated. Moreover, the nomogram was validated by assessing its discrimination and calibration. Results In these patients, age at diagnosis, the extent of tumor resection, radiotherapy, and chemotherapy were included in the multivariate Cox regression model. Based on this multivariate Cox regression model, a nomogram of 1-year overall survival for atypical teratoid/rhabdoid tumor patients was generated. The nomogram had good discrimination (the concordance index was 0.781) and calibration curves showed no deviation from reference lines. Decision curve analysis demonstrated this nomogram was useful for clinical practice. The risk grouping system was built based on nomogram-derived risk scores, which could classify patients into 3 risk groups. Compared with the low-risk group, the risk of 1-year death was significantly higher in the intermediate-risk group (hazard ratio = 1.42, 95%, confidence intervals = 0.49-4.11) and high-risk group (hazard ratio = 9.78, 95% confidence intervals = 3.53-27.1). Conclusion A nomogram and risk grouping system were built to predict for the 1-year overall survival of atypical teratoid/rhabdoid tumor patients. The nomogram could facilitate a personalized prognostic evaluation for atypical teratoid/rhabdoid tumor patients and help medical practitioners make better treatment.

Background:Isolated frontosphenoidal craniosynostosis (IFSC) is rare, historically misdiagnosed as coronal synostosis due to phenotypic overlap. Traditionally viewed as sporadic, its genetic basis was largely unexplored. Recent identification of pathogenic FGFR3 variants in IFSC patients challenges this view, suggesting a genetic etiology and necessitating molecular evaluation. This study aims to establish a genetic association between premature cranial suture closure and variants of the FGFR3 gene. Case Description:This case report presents a rare instance of IFSC in a 10-month-old female infant, characterized by severe plagiocephaly due to premature fusion of the frontosphenoidal suture. Through high-resolution three-dimensional computed tomography imaging, the diagnosis was confirmed, and genetic testing revealed a heterozygous pathogenic FGFR3 missense variant (c.749C>G; p.Pro250Arg), previously associated with Muenke syndrome. This finding establishes a novel genetic association for IFSC, challenging the traditional view of its sporadic nature. The patient underwent successful unilateral fronto-orbital advancement and remodeling (FOAR), resulting in significant improvement in cranial symmetry. Conclusions:This case highlights the importance of molecular genetic testing in nonsyndromic craniosynostosis and the potential role of FGFR3 variants in IFSC. Early diagnosis and surgical intervention are crucial, advocating for a staged genetic testing approach in similar cases. These findings emphasize IFSC's genetic basis and its consideration in cranial deformity diagnoses.

In recent years, growing evidence indicates that the nervous system plays an indispensable role in tumor development and metastasis. Elucidating crosstalk between the nervous system and tumor progression has thrived as a hot topic and a new direction for understanding cancer pathogenesis. Notably, many novel discoveries have suggested that neurotransmitter receptors (NRs) are not only widely expressed in cancer cells, but also play key roles in regulating cancer initiation and progression by diverse approaches. In this review, we summarized the latest advance in cancer neuroscience, especially emphasizing the important roles of different NRs in cancer development and prevention. The exemplary studies presented herein illustrate the emerging view that NRs are profoundly influential, manifested in tumor growth, apoptosis, angiogenesis, metastasis, resistance to drugs, and participate in the formation of neural–cancer interactions. In addition, NRs also regulate cellular metabolic processes and tumor microenvironment (TME) remodeling. More importantly, numerous basic and clinical studies have suggested that NRs may be potential targets for cancer treatments, and corresponding agonists or antagonists have been identified effectively in controlling tumor growth and metastasis. In conclusion, NRs are emerging as novel targets for anti-cancer drug exploration and clinical cancer treatments, while trying to uncover deeper mechanisms and connections between NRs and cancer is of high clinical significance and translational value.

Focused microwave hyperthermia is a noninvasive, non-ionizing, and accurate treatment method that is promising for dealing with many kinds of cancers. Although focused microwave brain hyperthermia (FMBH) has been studied by some previous works, experimental evaluation of this technique in a practical experimental context has not been reported. This article aims to address this issue by developing a preclinical system prototype of FMBH and performing systematic experimental evaluation using several realistic head phantoms. We designed a 1.3-GHz hyperthermia applicator with 17 antennas and built nine different head phantoms based on a real human skull. We perform electromagnetic and thermal simulations and prove that the designed applicator can reliably achieve a good focused field and 45 $^{\circ}$ C temperature at the tumor. We then realize the FMBH system prototype and experimentally test the performance by applying fabricated 3-D head phantoms. The measured temperature results demonstrate that the FMBH system prototype is able to selectively treat the tumor. We also prove that the temperature at the tumor can be controlled at a constant level for a demanded time period for hyperthermia. This work provides a valuable experimental demonstration of the FMBH technique and is meaningful for its future development and clinical applications.