MFCC-CNN: A patient-independent seizure prediction model.

BACKGROUND: Automatic prediction of seizures is a major goal in the field of epilepsy. However, the high variability of Electroencephalogram (EEG) signals in different patients limits the use of prediction models in clinical applications. METHODS: This paper proposes a patient-independent seizure prediction model, named MFCC-CNN, to improve the generalization ability. MFCC-CNN model introduces Mel-Frequency Cepstrum Coefficients (MFCC) features and Linear Predictive Cepstral Coefficients (LPCC) features concentrated in the low frequency region, which contains more detailed information. Convolutional neural network (CNN) is used to construct a seizure prediction model. RESULTS: Experimental results showed that the proposed model obtained accuracy of 96 % , sensitivity of 92 % , specificity of 84 % and F1-score of 85 % for 24 cases in CNHB-MIT dataset. The overall performance of MFCC-CNN model is better than the other models. CONCLUSION: MFCC-CNN model does not need to be specifically customized for different patients. As a patient-independent seizure prediction model, it has good generalization ability.

Benchmarking Large Language Models for Cervical Spondylosis.

Cervical spondylosis is the most common degenerative spinal disorder in modern societies. Patients require a great deal of medical knowledge, and large language models (LLMs) offer patients a novel and convenient tool for accessing medical advice. In this study, we collected the most frequently asked questions by patients with cervical spondylosis in clinical work and internet consultations. The accuracy of the answers provided by LLMs was evaluated and graded by 3 experienced spinal surgeons. Comparative analysis of responses showed that all LLMs could provide satisfactory results, and that among them, GPT-4 had the highest accuracy rate. Variation across each section in all LLMs revealed their ability boundaries and the development direction of artificial intelligence.

Interleukin-7 expression by CAR-T cells improves CAR-T cell survival and efficacy in chordoma.

Chordoma is a rare bone tumor that frequently recurs after surgery, and the prognosis is poor with current treatments. This study aimed to identify potential novel immunotherapeutic targets for chordomas by identifying target proteins in clinical samples as well as tumor microenvironmental factors to enhance efficacy. Fourteen chordoma samples were analyzed by single-cell RNA sequencing, and B7-H3 and IL-7 were identified as potential targets and potentiators, respectively. B7-H3-targeted chimeric antigen receptor T (CAR-T) cells and B7-H3 CAR-T cells expressing IL-7 were synthesized and their anti-tumor activity evaluated in vitro, including in primary chordoma organoid models. The B7-H3 CAR-T/IL-7 therapy showed enhanced cytotoxicity and prolonged duration of action against tumor cells. Additionally, IL-7 modulated favorable subpopulations of cultured CAR-T cells, diminished immune checkpoint expression on T-cell surfaces, and enhanced T-cell functionality. The incorporation of IL-7 molecules into the B7-H3 CAR structure augmented CAR-T-cell function and improved CAR-T-cell efficacy, thus providing a novel dual therapeutic strategy for chordoma treatment.

Spinal neurenteric cysts: experience with 9 cases via an anterior cervical approach.

OBJECTIVE: Intraspinal cysts are uncommon, and the success rate of complete resection is still low for spinal neurenteric cysts (NCs). The aim of this study was to evaluate the efficacies of an anterior microscopic surgical approach in the treatment of ventral and ventrolateral subaxial cervical NCs (SCNCs). METHODS: Between 2019 and 2022, 9 patients with NCs of the subaxial spine underwent an anterior microsurgical approach. Their clinical presentations, radiological features, operative findings, and follow-up data were retrospectively reviewed and analyzed. RESULTS: All spinal cysts were intradural and extramedullary in origin. Five patients were first-time cases while 4 patients with recurrence underwent revision surgery. The most common clinical manifestation was pain (77.78%). One patient was found to have a concomitant disorder of Klippel-Feil syndrome. Microscopically confirmed gross-total resection was achieved in 8 patients (88.89%) based on clinical comparisons between pre- and postoperative MRI and intraoperative video. One patient had symptom recurrence 1 year after subtotal resection, while there was no evidence of recurrence during follow-up for the other patients. Dense adhesions within the spinal cord were observed in 8 patients (88.89%) intraoperatively. Most importantly, the surgical outcome was significantly improved in all patients, and the mean (± SE) Japanese Orthopaedic Association score increased from 11.33 ± 0.91 preoperatively to 16.22 ± 0.32 postoperatively (p = 0.008). CONCLUSIONS: An anterior surgical approach was proven to be both safe and effective in treating the ventral or ventrolateral SCNCs. The authors believe that an anterior microsurgical approach should be considered as a useful approach especially in patients with ventral recurrent SCNCs. Its clinical efficacy compared with a posterior approach in ventral spinal cyst may be better as most of the neurenteric cysts are ventrally or ventrolaterally located.

Stability in change: building a stable ecological security pattern in Northeast China under climate and land use changes.

Climate change and land use change caused by human activities have a profound impact on ecological security. Simulating the spatio-temporal changes in ecosystem service value and ecological security patterns under different carbon emission scenarios in the future is of great significance for formulating sustainable development policies. This study quantified the four major ecosystem services (habitat quality, water retention, soil erosion, and carbon storage) in Northeast China (NC), identified ecological source areas, and constructed a stable ecological security pattern. The results show that the spatial patterns of soil erosion, carbon storage, water retention, and habitat quality, the four major ecosystem services in NC, are relatively stable in the next 30 years, and there is no significant difference from the current spatial pattern distribution. The SSP1-2.6 carbon emission scenario is a priority model for the development of NC in the next 30 years. In this carbon emission scenario, the NC has the largest ecological resources (191,177 km2) and the least comprehensive resistance value (850.006 × 10-4). At the same time, the relative resistance of the corridor in this scenario is the smallest, and the area of the mandatory reserve pinch points is the least. The ecological corridors in the SSP1-2.6 scenario form a network distribution among the ecological sources, connecting several large ecological sources as a whole. This study fills the knowledge gap in building a stable ecological security pattern in NC under the background of global change, and provides a scientific basis for the decision-making of regional ecological security and land resource management.

Trehalose and its dihydrate: terahertz insights from solid to solution states.

Carbohydrates are pivotal biomolecules in biochemistry; this study employs terahertz time-domain spectroscopy (THz-TDS) to investigate the spectral characteristics of trehalose and its hydrate across the 0.1 to 2.2 THz frequency range. Notable differences in spectra between the two compounds were observed. Density Functional Theory (DFT) simulations of the crystal structure were conducted to elucidate this phenomenon. The consistency between experimental results and simulations substantiates the reliability of the experimental findings. Additionally, the spectral characteristics of these carbohydrates in solution were examined using microfluidic chip technology. This approach facilitates a comprehensive comparison of their behaviors in both solid and solution states.

Rumen microbiome-driven insight into bile acid metabolism and host metabolic regulation.

Gut microbes play a crucial role in transforming primary bile acids (BAs) into secondary forms, which influence systemic metabolic processes. The rumen, a distinctive and critical microbial habitat in ruminants, boasts a diverse array of microbial species with multifaceted metabolic capabilities. There remains a gap in our understanding of BA metabolism within this ecosystem. Herein, through the analysis of 9371 metagenome-assembled genomes and 329 cultured organisms from the rumen, we identified two enzymes integral to BA metabolism: 3-dehydro-bile acid delta4,6-reductase (baiN) and the bile acid:Na + symporter family (BASS). Both in vitro and in vivo experiments were employed by introducing exogenous BAs. We revealed a transformation of BAs in rumen and found an enzyme cluster, including L-ribulose-5-phosphate 3-epimerase and dihydroorotate dehydrogenase. This cluster, distinct from the previously known BA-inducible operon responsible for 7α-dehydroxylation, suggests a previously unrecognized pathway potentially converting primary BAs into secondary BAs. Moreover, our in vivo experiments indicated that microbial BA administration in the rumen can modulate amino acid and lipid metabolism, with systemic impacts underscored by core secondary BAs and their metabolites. Our study provides insights into the rumen microbiome's role in BA metabolism, revealing a complex microbial pathway for BA biotransformation and its subsequent effect on host metabolic pathways, including those for glucose, amino acids, and lipids. This research not only advances our understanding of microbial BA metabolism but also underscores its wider implications for metabolic regulation, offering opportunities for improving animal and potentially human health.

A novel computed tomography scoring system for evaluating the risk of dural defects in anterior surgery for cervical ossification of the posterior longitudinal ligament.

OBJECTIVE: To develop and validate a computed tomography (CT)-based scoring system for evaluating the risk of dural defects (DDs) in anterior surgery for cervical ossification of the posterior longitudinal ligament (OPLL). METHODS: We retrospectively analyzed CT imaging features of 114 OPLL patients in our institute who received anterior decompression surgery. Intraoperative DDs were found in 16 patients. A multivariable logistic regression was used to evaluate the predictors. According to the odd ratio of the included risk factors, we developed a CT scoring system for evaluating the risk of DDs in anterior OPLL surgery. The system was further validated in an independent group of 39 OPLL patients. RESULTS: We developed a CT scoring system as follows: hook sign (2 points), K-line (-) (1 point) and broad base (1 point). Thus, the system comprised 4 total points, and patients were at high risks of dural defects when the score ≥3 points. The operating characteristics of a score ≥3 for predicting DDs in the validation group were: sensitivity of 0.83, specificity of 0.94, LR positive of 13.75, LR negative of 0.18 and AUC of 0.886. The discriminatory ability of the proposed score could be demonstrated in the validation cohort. CONCLUSIONS: The relatively simple and easy-to-use scoring system we propose integrates the 3 most reliable spinal CT findings observed in patients with OPLL and a DD. The likelihood to identify the underlying risks of spinal CSF leaks may be useful to triage patients who may benefit from indirect decompression techniques.

Single-cell sequencing reveals VEGFR as a potential target for CAR-T cell therapy in chordoma.

BACKGROUND: Chordomas are rare osseous neoplasms with a dismal prognosis when they recur. Here we identified cell surface proteins that could potentially serve as novel immunotherapeutic targets in patients with chordoma. METHODS: Fourteen chordoma samples from patients attending Xuanwu Hospital Capital Medical University were subjected to single-cell RNA sequencing. Target molecules were identified on chordoma cells and cancer metastasis-related signalling pathways characterised. VEGFR-targeting CAR-T cells and VEGFR CAR-T cells with an additional TGF-ß scFv were synthesised and their in vitro antitumor activities were evaluated, including in a primary chordoma organoid model. RESULTS: Single-cell transcriptome sequencing identified the chordoma-specific antigen VEGFR and TGF-ß as therapeutic targets. VRGFR CAR-T cells and VEGFR/TGF-ß scFv CAR-T cells recognised antigen-positive cells and exhibited significant antitumor effects through CAR-T cell activation and cytokine secretion. Furthermore, VEGFR/TGF-ß scFv CAR-T cells showed enhanced and sustained cytotoxicity of chordoma cell lines in vitro compared with VRGFR CAR-T cells. CONCLUSIONS: This study provides a comprehensive single-cell landscape of human chordoma and highlights its heterogeneity and the role played by TGF-ß in chordoma progression. Our findings substantiate the potential of VEGFR as a target for CAR-T cell therapies in chordoma which, together with modulated TGF-ß signalling, may augment the efficacy of CAR-T cells.

Distribution and protection of Thesium chinense Turcz. under climate and land use change.

Wild medicinal plants are prominent in the field of Traditional Chinese Medicine (TCM), but their availability is being impacted by human activities and ecological degradation in China. To ensure sustainable use of these resources, it is crucial to scientifically plan areas for wild plant cultivation. Thesium chinense, a known plant antibiotic, has been overharvested in recent years, resulting in a sharp reduction in its wild resources. In this study, we employed three atmospheric circulation models and four socio-economic approaches (SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5) to investigate the primary environmental factors influencing the distribution of T. chinense. We also examined changes in its suitable area using the Biomod2 package. Additionally, we utilized the PLUS model to project and analyze future land use changes in climate-stable regions for T. chinense. Our planning for wild tending areas of T. chinense was facilitated by the ZONATION software. Over the next century, the climate-stable regions for T. chinense in China is approximately 383.05 × 104 km2, while the natural habitat in this region will progressively decline. Under the current climate conditions, about 65.06% of the habitats in the high suitable areas of T. chinense are not affected by future land use changes in China. Through hotspot analysis, we identified 17 hotspot cities as ideal areas for the wild tending of T. chinense, including 6 core hotspot cities, 6 sub-hotspot cities, and 5 fringe hotspot cities. These findings contribute to a comprehensive research framework for the cultivation planning of T. chinense and other medicinal plants.

A Global Bibliometric and Visualization Analysis of Craniovertebral Junction Bony Abnormalities Based on VOSviewer and Citespace.

OBJECTIVE: Recent years have witnessed a rapidly growing interest in CVJ bony abnormalities, and a qualitative and quantitative analysis of relevant literatures is necessary. This study aims to identify and summarize the published articles related to craniovertebral junction bony abnormalities, to analyze and visualize the current research trends and major contributors. METHODS: We collected data from Web of Science, excluding certain article types. Two researchers screened articles for relevance. Data were organized with EndnoteX9, and analyzed using VOSviewer and CiteSpace for co-authorship, co-occurrence, keyword burst, and co-citation analyses to identify research trends and collaborations. RESULTS: A total of 2,776 articles were included, revealing an increasing trend in annual publications of CVJ bony abnormalities. The USA was the leading country. King Edward Memorial Hospital was the most prolific institution, and Seth GS Medical College had the most citations. The Spine is the most popular journal with the highest number of publications and citations. Professor Goel Atul from India emerged as the most influential pioneer in this field. Keyword analysis highlighted surgical techniques, diagnosis, and anatomy as the primary research hotspots and Fixation, Placement, and Basilar invagination gradually become the new research trend. However, there is a relative weakness in basic research and epidemiology. CONCLUSIONS: This study provides valuable insights into the current research trends and critical contributors in CVJ bony abnormalities, guiding evidence-based decisions and fostering international collaborations to advance knowledge in this field.

Cleavage of the pseudoprotease iRhom2 by the signal peptidase complex reveals an ER-to-nucleus signaling pathway.

iRhoms are pseudoprotease members of the rhomboid-like superfamily and are cardinal regulators of inflammatory and growth factor signaling; they function primarily by recognizing transmembrane domains of their clients. Here, we report a mechanistically distinct nuclear function of iRhoms, showing that both human and mouse iRhom2 are non-canonical substrates of signal peptidase complex (SPC), the protease that removes signal peptides from secreted proteins. Cleavage of iRhom2 generates an N-terminal fragment that enters the nucleus and modifies the transcriptome, in part by binding C-terminal binding proteins (CtBPs). The biological significance of nuclear iRhom2 is indicated by elevated levels in skin biopsies of patients with psoriasis, tylosis with oesophageal cancer (TOC), and non-epidermolytic palmoplantar keratoderma (NEPPK); increased iRhom2 cleavage in a keratinocyte model of psoriasis; and nuclear iRhom2 promoting proliferation of keratinocytes. Overall, this work identifies an unexpected SPC-dependent ER-to-nucleus signaling pathway and demonstrates that iRhoms can mediate nuclear signaling.

Exploring terahertz spectral characteristics of L-sorbose and D-melibiose in solid and liquid states.

Saccharides are essential organic compounds that perform critical functions in sustaining life processes. As biomolecules, their vibrational frequencies predominantly fall in the terahertz (THz) range, making them amenable to analysis using THz techniques. In this study, L-sorbose and D-melibiose were measured using a THz time-domain spectroscopy system covering a frequency range of 0.1-2.0 THz, and their crystal structures were simulated using density functional theory. The experimental results demonstrated significant agreement with the simulation findings. In addition, the spectral properties of the two saccharides in solution were determined using microfluidic chip technology, thereby facilitating a comparison between the solid and aqueous states. The results demonstrate that the intramolecular and intermolecular interactions of the saccharides were weakened by the presence of water molecules, and the THz absorption spectrum of the same substance solution was found to be correlated with its concentration and temperature.

Vibrational spectroscopic detection and analysis of salicylic acid and aspirin binary cocrystal.

Salicylic acid is a raw material for preparing aspirin and holds an important position in medical history. Studying the crystallization of these two drugs is of great significance in improving their dissolution rate, bioavailability, and physical stability. Although various techniques have been used for structural characterization, there is still a lack of information on the collective vibrational behavior of aspirin and salicylic acid eutectic compounds. Firstly, two starting materials (salicylic acid and aspirin) were ground in a 1:1 M ratio to prepare eutectic compounds. The eutectic composition was studied using vibrational spectroscopy techniques, such as X-ray powder diffusion (XRPD), terahertz time-domain spectroscopy (THz-TDS), and Raman spectroscopy. Additionally, the structure of the aspirin and salicylic acid eutectic was simulated and optimized using density functional theory. It was found that the eutectic type II was the most consistent with the experiment, and the corresponding vibration modes of each peak were provided. These results offer a unique method for characterizing the structural composition of eutectic crystals, which can be utilized to enhance the physical and chemical properties, as well as the pharmacological activity, of specific drugs at the molecular level.

Exploring the metabolomic landscape: Perilla frutescens as a promising enhancer of production, flavor, and nutrition in Tan lamb meat.

Addressing health-related concerns linked to the metabolite profile of lamb meat has become paramount, in line with the growing demand for enhanced flavor and taste. We examined the impact of Perilla frutescens seeds on Tan lamb growth, carcass traits, and metabolite profiles. Three diets were employed: a low-concentrate group (LC), a high-concentrate group (HC), and a PFS group (the LC diet supplemented with 3% Perilla frutescens seeds) on a dry matter basis. Forty-five male Tan-lambs (approximately six months) with similar body weights (25.1 kg ± 1.12 SD) were randomly assigned to one of these three groups for 84-day feeding, including an initial 14-day adjustment phase. The supplementation of PFS resulted in increased average daily gain (P < 0.01) and improved carcass quality and meat color (P < 0.05). Additionally, it led to an enhancement in omega-3 polyunsaturated fatty acids (P < 0.05) and a reduction in the omega-6/omega-3 ratio (P < 0.05). Using gas chromatography-mass spectrometry, 369 volatile compounds were identified with enhanced levels of acetaldehyde and 1,2,4-trimethyl-benzene associated with PFS (P < 0.05). Among the 807 compounds identified by ultra-high performance liquid chromatography-mass spectrometry, there were 66 significantly differential compounds (P < 0.05), including 43 hydrophilic metabolites and 23 lipids. PFS supplementation led to significant alterations in 66 metabolites, with three metabolites including 2,5-diisopropyl-3-methylphenol, 3-hydroxydecanoic acid, and lysophosphatidylcholine (15:0) emerging as potential PFS-related biomarkers. The study indicates that PFS supplementation can enhance Tan-lamb growth, feed efficiency, and meat quality, potentially providing lamb meat with improved flavor and nutritional characteristics.