Structural- and DTI- MRI enable automated prediction of IDH Mutation Status in CNS WHO Grade 2-4 glioma patients: a deep Radiomics Approach.

BACKGROUND: The role of isocitrate dehydrogenase (IDH) mutation status for glioma stratification and prognosis is established. While structural magnetic resonance image (MRI) is a promising biomarker, it may not be sufficient for non-invasive characterisation of IDH mutation status. We investigated the diagnostic value of combined diffusion tensor imaging (DTI) and structural MRI enhanced by a deep radiomics approach based on convolutional neural networks (CNNs) and support vector machine (SVM), to determine the IDH mutation status in Central Nervous System World Health Organization (CNS WHO) grade 2-4 gliomas. METHODS: This retrospective study analyzed the DTI-derived fractional anisotropy (FA) and mean diffusivity (MD) images and structural images including fluid attenuated inversion recovery (FLAIR), non-enhanced T1-, and T2-weighted images of 206 treatment-naïve gliomas, including 146 IDH mutant and 60 IDH-wildtype ones. The lesions were manually segmented by experienced neuroradiologists and the masks were applied to the FA and MD maps. Deep radiomics features were extracted from each subject by applying a pre-trained CNN and statistical description. An SVM classifier was applied to predict IDH status using imaging features in combination with demographic data. RESULTS: We comparatively assessed the CNN-SVM classifier performance in predicting IDH mutation status using standalone and combined structural and DTI-based imaging features. Combined imaging features surpassed stand-alone modalities for the prediction of IDH mutation status [area under the curve (AUC) = 0.846; sensitivity = 0.925; and specificity = 0.567]. Importantly, optimal model performance was noted following the addition of demographic data (patients' age) to structural and DTI imaging features [area under the curve (AUC) = 0.847; sensitivity = 0.911; and specificity = 0.617]. CONCLUSIONS: Imaging features derived from DTI-based FA and MD maps combined with structural MRI, have superior diagnostic value to that provided by standalone structural or DTI sequences. In combination with demographic information, this CNN-SVM model offers a further enhanced non-invasive prediction of IDH mutation status in gliomas.

Discovery of new tricyclic spiroindole derivatives as potent P-glycoprotein inhibitors for reversing multidrug resistance enabled by a synthetic methodology-based library.

The discovery of novel and highly effective P-gp inhibitors is considered to be an effective strategy for overcoming tumor drug resistance. In this paper, a phenotypic screening via a self-constructed synthetic methodology-based library identified a new class of tricyclic spiroindole derivatives with excellent tumor multidrug resistance reversal activity. A stereospecific compound OY-103-B with the best reversal activity was obtained based on a detailed structure-activity relationship study, metabolic stability optimization and chiral resolution. For the VCR-resistant Eca109 cell line (Eca109/VCR), co-administration of 5.0 µM OY-103-B resulted in a reversal fold of up to 727.2, superior to the typical third-generation P-gp inhibitor tariquidar. Moreover, the compound inhibited the proliferation of Eca109/VCR cells in a concentration-dependent manner in plate cloning and flow cytometry. Furthermore, fluorescence substrate accumulation assay and chemotherapeutic drug reversal activity tests demonstrated that OY-103-B reversed tumor drug resistance via P-gp inhibition. In conclusion, this study provides a novel skeleton that inspires the design of new P-gp inhibitors, laying the foundation for the treatment of drug-resistant tumors.

Enhancing endometrial receptivity: the roles of human chorionic gonadotropin in autophagy and apoptosis regulation in endometrial stromal cells.

Inadequate endometrial receptivity often results in embryo implantation failure and miscarriage. Human chorionic gonadotropin (hCG) is a key signaling molecule secreted during early embryonic development, which regulates embryonic maternal interface signaling and promotes embryo implantation. This study aimed to examine the impact of hCG on endometrial receptivity and its underlying mechanisms. An exploratory study was designed, and endometrial samples were obtained from women diagnosed with simple tubal infertility or male factor infertile (n = 12) and recurrent implantation failure (RIF, n = 10). Using reverse transcription-quantitative PCR and western blotting, luteinizing hormone (LH)/hCG receptor (LHCGR) levels and autophagy were detected in the endometrial tissues. Subsequently, primary endometrial stromal cells (ESCs) were isolated from these control groups and treated with hCG to examine the presence of LHCGR and markers of endometrial receptivity (HOXA10, ITGB3, FOXO1, LIF, and L-selectin ligand) and autophagy-related factors (Beclin1, LC3, and P62). The findings revealed that the expressions of receptivity factors, LHCGR, and LC3 were reduced in the endometrial tissues of women with RIF compared with the control group, whereas the expression of P62 was elevated. The administration of hCG to ESCs specifically activated LHCGR, stimulating an increase in the endometrial production of HOXA10, ITGB3, FOXO1, LIF and L-selectin ligands. Furthermore, when ESCs were exposed to 0.1 IU/mL hCG for 72 h, the autophagy factors Beclin1 and LC3 increased within the cells and P62 decreased. Moreover, the apoptotic factor Bax increased and Bcl-2 declined. However, when small interfering RNA was used to knock down LHCGR, hCG was less capable of controlling endometrial receptivity and autophagy molecules in ESCs. In addition, hCG stimulation enhanced the phosphorylation of ERK1/2 and mTOR proteins. These results suggest that women with RIF exhibit lower levels of LHCGR and compromised autophagy function in their endometrial tissues. Thus, hCG/LHCGR could potentially improve endometrial receptivity by modulating autophagy and apoptosis.

Effect of radiation cross-linked collagen scaffold in alveolar ridge preservation of extraction socket.

This study aimed to evaluate the properties of radiation cross-linked collagen scaffold (RCS) and its efficacy for alveolar ridge preservation (ARP). RCS was prepared from collagen dispersion by electron beam irradiation and freeze-drying. The microstructure, swelling ratio, area alteration and mechanical properties of RCS were characterized. Fifty-four New Zealand rabbits performing incisor extraction on maxilla and mandible were randomly assigned into positive, sham operation or treatment groups. Micro-computed tomography (micro-CT) scans, performed after 1, 4, and 12 weeks of surgery, were to assess changes in ridge height at buccal and palatal side, in ridge width and in micromorphological parameters. Histological analysis accessed socket microarchitecture. The results showed that RCS had stable mechanical properties and morphologic features that provided a reliable physical support for ARP. Dimensional changes in treatment group revealed significantly greater vertical height at buccal (5.32 [3.37, 7.26] mm, p < .0001) and palatal (4.37 [2.66, 6.09] mm, p < .0001) side, and horizontal width at the maxilla (0.16 [0.04, 0.28] mm, p < .01) and mandible (0.33 [0.11, 0.54] mm, p < .01) than those in sham operation group after 12 weeks. The treatment group had advantage than positive group in vertical height preservation, quantitatively. The order and density of bone trabeculae were improved in treatment group. These findings indicated that RCS had the potential to serve as an effective scaffold for ARP.

Recombinant human collagen I/carboxymethyl chitosan hydrogel loaded with long-term released hUCMSCs derived exosomes promotes skin wound repair.

BACKGROUND: Stem cell exosomes are beneficial in accelerating wound repair. However, the therapeutic function is limited due to its rapid clearance in vivo. To improve the functionality of exosomes in cutaneous wound healing, a novel hydrogel was designed and fabricated by recombinant human collagen I and carboxymethyl chitosan loaded with exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs), named as the rhCol I/CMC-Exos hydrogel. METHODS: Exosomes were extracted from hUCMSCs and were characterizated by TEM (Transmission Electron Microscopy), and biomarker detection. The rhCol I hydrogel, rhCol I/carboxymethyl chitosan (rhCol I/CMC) hydrogel and the rhCol I/CMC-Exos hydrogel composites were cross-linked by genipin. These materials were assessed and compared for their physical characteristics, including cross-sectional morphology, porosity, pore distribution, and hydrophilicity. Cell biocompatibility on biomaterials was investigated using scanning electron microscopy and CFDA staining, as well as assessed in vivo through histological examination of major organs in mice. Effects of the hydrogel composite on wound healing were further evaluated by using the full-thickness skin defect mice model. RESULTS: Successful extraction of hUCMSCs-derived exosomes was confirmed by TEM，Western Blotting and flow cytometry. The synthesized rhCol I/CMC-Exos hydrogel composite exhibited cytocompatibility and promoted cell growth in vitro. The rhCol I/CMC-Exos hydrogel showed sustained release of exosomes. In the mice full skin-defects model, the rhCol I/CMC-Exos-treated group showed superior wound healing efficiency, with 15 % faster wound closure compared to controls. Histological examinations revealed thicker dermis formation and more balanced collagen deposition in wounds treated with rhCol I/CMC-Exos hydrogel. Mechanistically, the application of rhCol I/CMC-Exos hydrogel increased fibroblasts proliferation, alleviated inflammation responses as well as promoted angiogenesis, thereby was beneficial in promoting skin wound healing and regeneration. CONCLUSION: Our study, for the first time, introduced recombinant human Collagen I in fabricating a novel hydrogel loaded with hUCMSCs-derived exosomes, which effectively promoted skin wound closure and regeneration, demonstrating a great potential in severe skin wound healing treatment.

Prognostic Value of Fibrinogen to Prealbumin Ratio (FPR) in Resectable Gastric Cancer.

Background: The ratio of fibrinogen to prealbumin (FPR) is associated with the prognosis of many cancers. However, the prognostic significance of FPR in resectable gastric cancer has not been clarified. Methods: A total of 760 patients with resectable gastric cancer participated in this study. The receiver operating characteristic curve (ROC) was used to calculate the optimal cutoff value of each immunonutrition marker. Univariate and multivariate Cox regression analyses were used to confirm the prognostic value of FPR in patients with gastric cancer and to select appropriate variables for the construction of nomogram. Results: Utilizing ROC analysis, we calculated the optimal cutoff value for FPR and stratified 760 patients into high and low FPR groups. Subsequent examination revealed notable distinctions in baseline characteristics between these groups. For instance, Patients with higher FPR tend to be older and have more lymph node metastasis. Statistical analysis through the chi-square test confirmed the significance of these differences (P < 0.05). In addition, the results of the multivariate Cox proportional hazards regression analysis indicate that the factors related to OS were age (P = 0.001), T stage (P < 0.001), N stage (P < 0.001), radical resection (P < 0.001), and FPR (P < 0.024). The nomogram is composed of the above five variables. ROC analysis showed that the area under the curve (AUC) of the nomogram was 0.859 (95% CI: 0.831-0.887), and the sensitivity and specificity were 77.4% and 82.1%, respectively. Conclusion: FPR is a potential marker in patients with resectable gastric cancer. The nomogram based on FPR shows good predictive ability, which is helpful for clinicians to judge the prognosis of patients and choose targeted treatment strategies.

Research overview on the genetic mechanism underlying the biosynthesis of polysaccharide in tuber plants.

Tuber plants are of great significance in the world as human food crops. Polysaccharides, important metabolites in tuber plants, also serve as a source of innovative drugs with significant pharmacological effects. These drugs are particularly known for their immunomodulation and antitumor properties. To fully exploit the potential value of tuber plant polysaccharides and establish a synthetic system for their targeted synthesis, it is crucial to dissect their metabolic processes and genetic regulatory mechanisms. In this article, we provide a comprehensive summary of the basic pathways involved in the synthesis of various types of tuber plant polysaccharides. We also outline the key research progress that has been made in this area in recent years. We classify the main types and functions of tuber plant polysaccharides and analyze the biosynthetic processes and genetic regulation mechanisms of key enzymes involved in the metabolic pathways of starch, cellulose, pectin, and fructan in tuber plants. We have identified hexokinase and glycosyltransferase as the key enzymes involved in the polysaccharide synthesis process. By elucidating the synthesis pathway of polysaccharides in tuber plants and understanding the underlying mechanism of action of key enzymes in the metabolic pathway, we can provide a theoretical framework for enhancing the yield of polysaccharides and other metabolites in plant culture cells. This will ultimately lead to increased production efficiency.

Study on the underlying molecular mechanism of benzene-induced nervous system damage in mice based on tandem mass tag (TMT) proteomics.

Benzene is known to be a common toxic industrial chemical, and prolonged benzene exposure may cause nervous system damage. At present, there were few studies on benzene-induced neurological damage. This research aimed to identify the protein biomarkers to explore the mechanism of nervous system damage caused by benzene. We established a benzene poisoning model of C57 mice by gavage of benzene-peanut oil suspension and identified differentially expressed proteins (DEPs) in brain tissue using tandem mass tag (TMT) proteomics. The results showed a significant weight loss and decrease in leukocyte and neutrophil counts in benzene poisoning mice compared to the control group. We also observed local cerebral oedema and small vessel occlusion in the cerebral white matter of benzene poisoning mice. TMT proteomic results showed that a total 6,985 proteins were quantified, with a fold change (FC) > 1.2 (or < 1/1.2) and P value <0.05 were considered as DEPs. Compared with the control group, we identified 43 DEPs, comprising 14 upregulated and 29 downregulated proteins. Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis results showed that the candidate proteins were mainly involved in cholesterol metabolism, complement and coagulation cascades, african trypanosomiasis, PPAR signaling pathway, and vitamin digestion and absorption. Three proteins, 2-hydroxyacylsphingosine 1-beta-galactosyltransferase (UGT8), Apolipoprotein A-I (APOA1) and Complement C3 (C3) were validated using immunoblotting and immunohistochemical. In conclusion, our study preliminarily investigated the mechanism of benzene toxicity to the nervous system by analyzing DEPs changes in the brain.

Modular Synthesis of Improbable Rotaxanes with All-Benzene Scaffolds.

"Improbable" rotaxanes consisting of interlocked conjugated components represent non-trivial synthetic targets, not to mention those with all-benzene scaffolds. Herein, a modular synthetic strategy has been established using an isolable azo-linked pre-rotaxane as the core module, in which the azo group functions as a tracelessly removable template to direct mechanical bond formations. Through versatile connections of the pre-rotaxane and other customizable modules, [2]- and [3]rotaxanes derived from all-benzene scaffolds have been accomplished, demonstrating the utility and potential of the synthetic design for all-benzene interlocked supramolecules.

Focusing on the role of protein kinase mTOR in endometrial physiology and pathology: insights for therapeutic interventions.

The mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase crucial for cellular differentiation, proliferation, and autophagy. It shows a complex role in the endometrium, influencing both normal and pathogenic conditions. mTOR promotes the growth and maturation of endometrial cells, enhancing endometrial receptivity and decidualization. However, it also contributes to the development of endometriosis (EMs) and endometrial cancer (EC), thus emerging as a therapeutic target for these conditions. In this review, we summarize recent research progress on the mTOR signalling pathway in the endometrium. This provides insights into female endometrial structure and function and guides the prevention and treatment of related diseases.

Sinapine thiocyanate alleviates intervertebral disc degeneration by not regulating JAK1/STAT3/NLRP3 signal pathway.

BACKGROUND: Intervertebral disc degeneration (IDD) is a major cause of low back pain. Sinapine thiocyanate (ST) has been reported to have a wide range of biological activities. However, the treatment of IDD with ST has not been studied. OBJECTIVES: To explore the role and mechanism of ST treatment in IDD. MATERIAL AND METHODS: Nucleus pulposus cells (NPCs) were induced using lipopolysaccharide (LPS), which was used as an in vitro model of IDD. Cell activity, oxidative stress-related indicators and protein expression were detected using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, enzyme-linked immunosorbent assay (ELISA) and western blot. Pyroptosis was evaluated with propidium iodide (PI)/Hoechst double staining and immunofluorescence for NOD-like receptor protein 3 (NLRP3), and pyroptosis-related proteins and inflammatory factors were measured with western blot and ELISA. The pathological changes of IDD were assessed with hematoxylin & eosin (H&E) and safranin-O staining. RESULTS: Our results showed that ST alleviated LPS-induced degeneration of NPCs, as evidenced by reducing reactive oxygen species (ROS), malondialdehyde (MDA), matrix metalloproteinase-13 (MMP-13), a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), and increasing collagen II and aggrecan expression. Moreover, ST repressed LPS-induced pyroptosis by inhibiting NLRP3, caspase-1 p20, interleukin (IL)-1ß and IL-18. Further studies showed that ST did not restrain the activation of the JAK1/STAT3 signaling pathway induced by colivelin, or of the enhanced pyroptosis induced by polyphyllin VI. Sinapine thiocyanate alleviated IDD in vivo and suppressed NLRP3-mediated pyroptosis and the JAK1/STAT3 signaling pathway. CONCLUSIONS: Sinapine thiocyanate could alleviate IDD, although this did not include a reduction in NLRP3-mediated pyroptosis and inactivation of the JAK1/STAT3 signaling pathway, thus potentially being a candidate drug for IDD treatment.

Volume-based 18F-FDG PET/CT predicts prognosis and outcome of active surveillance for intra-abdominal desmoid tumor.

PURPOSE: Desmoid tumor (DT) is a rare monoclonal, fibroblastic proliferation characterized by a variable and often unpredictable clinical course. Initial active surveillance is recommended by current guideline, and surgery is one of the main therapies for DT. Predicting the prognosis and outcome of active surveillance for intra-abdominal DT is pressing issue. METHODS: The study included eighteen patients with intra-abdominal DT. Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) were measured. We analyzed their relationship with the outcome of active surveillance, as well as clinical, prognostic, and pathological data. RESULTS: The MTV and TLG of recurrent DT were significantly higher than those of non-recurrent DT (P < 0.001 and P = 0.00, respectively). The ROC curve suggested that the appropriate cutoff values for distinguishing recurrent DT from non-recurrent DT were 760.8 for MTV (sensitivity = 1, specificity = 0.857 and AUC = 0.929), and 1318.4 for TLG (sensitivity = 1, specificity = 0.786, and AUC = 0.911). The cutoff values of MTV and TLG significantly correlated with PFS using the Kaplan-Meier method (P = 0.002 and P = 0.007, respectively). MTV and TLG could distinguish DTs with subsequent progression from stable ones (P = 0.004 and P = 0.004, respectively). The ROC curve suggested that the appropriate cutoff values for distinguishing DTs with subsequent progression from stable ones were 197.1 for MTV (sensitivity = 0.9, specificity = 1, and AUC = 0.900), and 445.45 for TLG (sensitivity = 0.9, specificity = 1, and AUC = 0.900). CONCLUSION: Volume-based 18F-FDG-PET can predict prognosis of intra-abdominal DT. MTV and TLG can predict the outcome of active surveillance for intra-abdominal DT. MTV and TLG can potentially be predictors of surgical risk and difficulty.

Machine learning analysis of human skin by optoacoustic mesoscopy for automated extraction of psoriasis and aging biomarkers.

Ultra-wideband raster-scan optoacoustic mesoscopy (RSOM) is a novel modality that has demonstrated unprecedented ability to visualize epidermal and dermal structures in-vivo. However, an automatic and quantitative analysis of three-dimensional RSOM datasets remains unexplored. In this work we present our framework: Deep Learning RSOM Analysis Pipeline (DeepRAP), to analyze and quantify morphological skin features recorded by RSOM and extract imaging biomarkers for disease characterization. DeepRAP uses a multi-network segmentation strategy based on convolutional neural networks with transfer learning. This strategy enabled the automatic recognition of skin layers and subsequent segmentation of dermal microvasculature with an accuracy equivalent to human assessment. DeepRAP was validated against manual segmentation on 25 psoriasis patients under treatment and our biomarker extraction was shown to characterize disease severity and progression well with a strong correlation to physician evaluation and histology. In a unique validation experiment, we applied DeepRAP in a time series sequence of occlusion-induced hyperemia from 10 healthy volunteers. We observe how the biomarkers decrease and recover during the occlusion and release process, demonstrating accurate performance and reproducibility of DeepRAP. Furthermore, we analyzed a cohort of 75 volunteers and defined a relationship between aging and microvascular features in-vivo. More precisely, this study revealed that fine microvascular features in the dermal layer have the strongest correlation to age. The ability of our newly developed framework to enable the rapid study of human skin morphology and microvasculature in-vivo promises to replace biopsy studies, increasing the translational potential of RSOM.

Nickel Nanoparticles Protruding from Molybdenum Carbide Micropillars with Carbon Layer-Protected Biphasic 0D/1D Heterostructures for Efficient Water Splitting.

It remains a tremendous challenge to achieve high-efficiency bifunctional electrocatalysts for both the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER) for hydrogen production by water splitting. Herein, a novel hybrid of 0D nickel nanoparticles dispersed on the one-dimensional (1D) molybdenum carbide micropillars embedded in the carbon layers (Ni/Mo2C@C) was successfully prepared on nickel foam by a facile pyrolysis strategy. During the synthesis process, the nickel nanoparticles and molybdenum carbide were simultaneously generated under H2 and C2H2 mixed atmospheres and conformally encapsulated in the carbon layers. Benefiting from the distinctive 0D/1D heterostructure and the synergistic effect of the biphasic Mo2C and Ni together with the protective effect of the carbon layer, the reduced activation energy barriers and fast catalytic reaction kinetics can be achieved, resulting in a small overpotential of 96 mV for the HER and 266 mV for the OER at the current density of 10 mA cm-2 together with excellent durability in 1.0 M KOH electrolyte. In addition, using the developed Ni/Mo2C@C as both the cathode and anode, the constructed electrolyzer exhibits a small voltage of 1.55 V for the overall water splitting. The novel designed Ni/Mo2C@C may give inspiration for the development of efficient bifunctional catalysts with low-cost transition metal elements for water splitting.

Analysis of the efficacy of upfront brain radiotherapy versus deferred radiotherapy for EGFR/ALK-positive non-small cell lung cancer with brain metastases: a retrospective study.

BACKGROUND: For brain metastases (BMs) from EGFR/ALK-positive non-small cell lung cancer (NSCLC), the best time to administer tyrosine kinase inhibitors (TKIs) and brain radiotherapy (RT) has not been identified. This analysis was an attempt to solve this problem in part. METHODS: A total of 163 patients with EGFR/ALK-positive NSCLC and brain metastasis (BM) who were diagnosed between January 2017 and July 2022 were included in this study. Ninety-one patients underwent upfront RT, and 72 patients received deferred RT. Comparing the clinical efficacy and safety in these two patient cohorts was the main goal of the study. RESULTS: The average follow-up period was 20.5 months (range 2.0 to 91.9 months). The median overall survival (OS) was 26.5 months, and the median intracranial progression-free survival (iPFS) was 23.6 months. Upfront RT considerably increased the iPFS (26.9 vs. 20.2 months, hazard ratio [HR] = 5.408, P = 0.020) and OS (31.2 vs. 22.3 months, HR = 4.667, P = 0.031) compared to deferred RT. According to multivariate analysis, upfront RT was an independent risk factor for predicting iPFS (HR = 1.670, P = 0.021). Upfront RT (HR = 1.531, P = 0.044), TKI therapy (HR = 0.423, P < 0.001), and oligometastases (HR = 2.052, P = 0.021) were found to be independent risk factors for OS. CONCLUSION: This study showed that upfront RT combined with TKI treatment can significantly improve intracranial disease management and prolong survival in patients with EGFR/ALK mutations in BMs from NSCLC.

The Brain Tumor Segmentation (BraTS) Challenge 2023: Focus on Pediatrics (CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs).

Pediatric tumors of the central nervous system are the most common cause of cancer-related death in children. The five-year survival rate for high-grade gliomas in children is less than 20%. Due to their rarity, the diagnosis of these entities is often delayed, their treatment is mainly based on historic treatment concepts, and clinical trials require multi-institutional collaborations. The MICCAI Brain Tumor Segmentation (BraTS) Challenge is a landmark community benchmark event with a successful history of 12 years of resource creation for the segmentation and analysis of adult glioma. Here we present the CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs 2023 challenge, which represents the first BraTS challenge focused on pediatric brain tumors with data acquired across multiple international consortia dedicated to pediatric neuro-oncology and clinical trials. The BraTS-PEDs 2023 challenge focuses on benchmarking the development of volumentric segmentation algorithms for pediatric brain glioma through standardized quantitative performance evaluation metrics utilized across the BraTS 2023 cluster of challenges. Models gaining knowledge from the BraTS-PEDs multi-parametric structural MRI (mpMRI) training data will be evaluated on separate validation and unseen test mpMRI dataof high-grade pediatric glioma. The CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs 2023 challenge brings together clinicians and AI/imaging scientists to lead to faster development of automated segmentation techniques that could benefit clinical trials, and ultimately the care of children with brain tumors.

Matrine suppresses hepatocellular carcinoma tumorigenesis by modulating circ_0055976/miR-1179/lactate dehydrogenase A axis.

BACKGROUND: Matrine has been identified to have anticancer activity in hepatocellular carcinoma (HCC). Circ_0055976 was highly expressed in HCC. Here, we investigated the function and relationship of Matrine and circ_0055976 in HCC tumorigenesis. METHODS: Cell proliferation and invasion were detected using Cell Counting Kit-8, 5-Ethynyl-2'-deoxyuridine (EdU), colony formation and transwell assays, respectively. Cell aerobic glycolysis was evaluated by detecting glucose consumption, lactate production, and the ratios of ATP/ADP. Levels of genes and proteins were detected by quantitative real-time polymerase chain reaction and Western blotting. The target relationship between miR-1179 and circ_0055976 or lactate dehydrogenase A (LDHA) was analyzed by dual-luciferase reporter assay. The mouse xenograft model was established to conduct the in vivo assay. RESULTS: Matrine suppressed HCC cell proliferation, invasion and anaerobic glycolysis in vitro. Circ_0055976 was highly expressed in HCC tissues and cells, and was reduced by Matrine treatment. Moreover, overexpression of circ_0055976 reversed the anticancer effects of Matrine in HCC cells. Mechanistically, circ_0055976/miR-1179/LDHA formed an axis. Circ_0055976 knockdown or miR-1179 overexpression impaired HCC cell proliferation, invasion, and anaerobic glycolysis, which were reversed by miR-1179 inhibition or LDHA overexpression. Meanwhile, forced expression of LDHA abolished the regulatory effects of Matrine on HCC cells. In the clinic, Matrine impeded HCC tumor growth in vivo, and this effect was boosted after circ_0055976 silencing. CONCLUSION: Matrine suppressed HCC cell proliferation, invasion, and anaerobic glycolysis via circ_0055976/miR-1179/LDHA axis, providing a new insight into the clinical application of Matrine in HCC treatment.

Development and validation of a prognostic nomogram for patients with laryngeal cancer with synchronous or metachronous lung cancer.

BACKGROUND: The objective of this study was to examine the independent prognostic factors of laryngeal cancer with synchronous or metachronous lung cancer (LCSMLC), and to generate and verify a clinical prediction model. METHODS: In this study, laryngeal cancer alone and LCSMLC were defined using the Surveillance, Epidemiology, and End Results (SEER) database. Risk factors of patients with LCSMLC were analyzed through univariate and multivariate logistic regression analysis. Independent prognostic factors were selected by Cox regression analyses, on the basis of which a nomogram was constructed using R code. Kaplan-Meier survival analyses were applied to test the application of a risk stratification system. Finally, we conducted a comparison of the American Joint Committee on Cancer (AJCC) staging system of laryngeal cancer with the new model of nomogram and risk stratification. For further validation of the nomogram, data from patients at two Chinese independent institutions were also analyzed. RESULTS: According to the eligibility criteria, 32 429 patients with laryngeal cancer alone and 641 patients with LCSMLC from the SEER database (the training cohort) and additional 61 patients from two Chinese independent institutions (the external validation cohort) were included for final analyses. Compared with patients with laryngeal cancer who did not have synchronous or metachronous lung cancer, age, sex, race, primary site of laryngeal cancer, grade, and stage were risk factors for LCSMLC, while marriage, surgery, radiation therapy, and chemotherapy are not their risk factors. Age, two cancers' interval, pathological type, stage, surgery, radiation, primary lung site, and primary throat site were independent prognostic predictors of LCSMLC. The risk stratification system of high-, medium-, and low-risk groups significantly distinguished the prognosis in different patients with LCSMLC, regardless of the training cohort or the validation cohort. Compared with the 6th AJCC TNM stage of laryngeal cancer, the new model of nomogram and risk stratification showed an improved net benefit. CONCLUSIONS: Age, sex, race, primary site of laryngeal cancer, grade, and stage were risk factors for LCSMLC. An individualized clinical prognostic predictive model by nomogram was generated and validated, which showed superior prediction ability for LCSMLC.

Florid reactive periostitis of the clavicle: A case report and literature review.

RATIONALE: Florid reactive periostitis (FRP), a rare reactive bone lesion, typically presents in the short tubular bones of the extremities, with infrequent occurrences in the long tubular bones. This report discusses a unique case of FRP in the clavicle, managed through comprehensive lesion debridement and bone grafting, yielding positive results over a 3-year duration. PATIENT CONCERN: A 25-year-old male presented with a discernible mass at the left sternal end of the clavicle, discovered incidentally 2 weeks prior. The patient exhibited no clinical signs of inflammation, pain, sinus tract, or suppuration. DIAGNOSIS: Initial pathological examination of the local excision suggested benign lesions, although malignancy could not be ruled out. A definitive diagnosis of clavicular FRP was reached post complete lesion resection, with supporting evidence from postoperative pathology, imaging, and clinical symptoms. INTERVENTION: The left clavicle was reconstructed through an open surgical procedure involving total mass removal and ipsilateral extraction of an iliac bone of suitable dimensions. This was implanted into the clavicular bone defect and internally fixed with a plate. OUTCOMES: Three years of consecutive follow-up revealed no recurrence of hyperplasia, absence of mass or tenderness at the left sternal end of the clavicle, and unimpaired function of adjacent joints. LESSONS: The primary clinical challenge with FRP is its diagnosis. While pathological diagnosis remains crucial, it is also important to incorporate imaging and clinical symptoms for a comprehensive assessment. Complete mass excision may offer specific benefits in distinguishing FRP from its malignant counterparts.

Exploring the conformational dynamics and thermodynamics of EGFR S768I and G719X + S768I mutations in non-small cell lung cancer: An in silico approaches.

Non-small cell lung cancer (NSCLC) is often driven by mutations in the epidermal growth factor receptor (EGFR) gene. However, rare mutations such as G719X and S768I lack standard anti-EGFR targeted therapies. Understanding the structural differences between wild-type EGFR and these rare mutants is crucial for developing EGFR-targeted drugs. We performed a systematic analysis using molecular dynamics simulations, essential dynamics (ED), molecular mechanics Poisson-Boltzmann surface area, and free energy calculation methods to compare the kinetic properties, molecular motion, and free energy distribution between wild-type EGFR and the rare mutants' structures G719X-EGFR, S768I-EGFR, and G719X + S768I-EGFR. Our results showed that S768I-EGFR and G719X + S768I-EGFR have higher global and local conformational flexibility and lower thermal and global structural stability than WT-EGFR. ED analysis revealed different molecular motion patterns between S768I-EGFR, G719X + S768I-EGFR, and WT-EGFR. The A-loop and αC-helix, crucial structural elements related to the active state, showed a tendency toward active state development, providing a molecular mechanism explanation for NSCLC caused by EGFR S768I and EGFR G719C + S768I mutations. The present study may be helpful in the development of new EGFR-targeted drugs based on the structure of rare mutations. Our findings may aid in developing new targeted treatments for patients with EGFR S768I and EGFR G719X + S768I mutations.