Specific plasma microRNA profiles could be potential non-invasive biomarkers for biochemical pregnancy loss following embryo transfer.

BACKGROUND: Plasma microRNAs act as biomarkers for predicting and diagnosing diseases. Reliable non-invasive biomarkers for biochemical pregnancy loss have not been established. We aim to analyze the dynamic microRNA profiles during the peri-implantation period and investigate if plasma microRNAs could be non-invasive biomarkers predicting BPL. METHODS: In this study, we collected plasma samples from patients undergoing embryo transfer (ET) on ET day (ET0), 11 days after ET (ET11), and 14 days after ET (ET14). Patients were divided into the NP (negative pregnancy), BPL (biochemical pregnancy loss), and CP (clinical pregnancy) groups according to serum hCG levels at day11~14 and ultrasound at day28~35 following ET. MicroRNA profiles at different time-points were detected by miRNA-sequencing. We analyzed plasma microRNA signatures for BPL at the peri-implantation stage, we characterized the dynamic microRNA changes during the implantation period, constructed a microRNA co-expression network, and established predictive models for BPL. Finally, the sequencing results were confirmed by Taqman RT-qPCR. RESULTS: BPL patients have distinct plasma microRNA profiles compared to CP patients at multiple time-points during the peri-implantation period. Machine learning models revealed that plasma microRNAs could predict BPL. RT-qPCR confirmed that miR-181a-2-3p, miR-9-5p, miR-150-3p, miR-150-5p, and miR-98-5p, miR-363-3p were significantly differentially expressed between patients with different reproductive outcomes. CONCLUSION: Our study highlights the non-invasive value of plasma microRNAs in predicting BPL.

Sequencing of the Complete Mitochondrial Genome of the Big Brown Mactra Clam, Mactra grandis (Venerida: Mactridae).

Mitochondrial genomes are playing an increasingly important role in molluscan taxonomy, germplasm, and evolution studies. The first complete mitochondrial genome of the commercial big brown mactra clam, Mactra grandis, was characterized using Illumina next-generation sequencing in this study. The 17,289 bp circular genome has a typical gene organization of 13 protein-coding genes (PCGs), 2 rRNAs, and 22 tRNAs, with an obvious (A + T)-bias of 64.54%. All PCGs exhibited a homogeneous bias in nucleotide composition with a (A + T)-bias, a positive GC skew, and a negative AT skew. Results of phylogenetic analysis showed that Mactra grandis was most closely related to Mactra cygnus. The functional gene arrangement of the two species was identical but different from other Mactra species. The congeneric relationships among Mactra species were demonstrated by genetic distance analysis. Additionally, the selective pressure analysis suggested that cox1 was highly efficient for discriminating closely related species in genus Mactra, while nad2 was the most appropriate marker for population genetic analysis.

Biomimetic Charge-Neutral Anion Receptors for Reversible Binding and Release of Highly Hydrated Phosphate in water.

Control of phosphate capture and release is vital in environmental, biological, and pharmaceutical contexts. However, the binding of trivalent phosphate (PO43-) in water is exceptionally difficult due to its high hydration energy. Based on the anion coordination chemistry of phosphate, in this study, four charge-neutral tripodal hexaurea receptors (L1 - L4), which were equipped with morpholine and PEG terminal groups to enhance their solubility in water, were synthesized to enable the pH-triggered phosphate binding and release in aqueous solutions. Encouragingly, the receptors were found to bind PO43- anion in a 1:1 ratio via hydrogen bonds in 100% water solutions, with L1 exhibiting the highest binding constant (1.2´103 M-1). These represent the first neutral anion ligands to bind phosphate in 100% water and demonstrate the potential for phosphate capture and release in water through pH-triggered mechanisms, mimicking native phosphate binding proteins. Furthermore, L1 can also bind multiple bioavailable phosphate species, which may serve as model systems for probing and modulating phosphate homeostasis in biological and biomedical researches.

A PET-based radiomics nomogram for individualized predictions of seizure outcomes after temporal lobe epilepsy surgery.

PURPOSE: To establish and validate a novel nomogram based on clinical characteristics and [18F]FDG PET radiomics for the prediction of postsurgical seizure freedom in patients with temporal lobe epilepsy (TLE). PATIENTS AND METHODS: 234 patients with drug-refractory TLE patients were included with a median follow-up time of 24 months after surgery. The correlation coefficient redundancy analysis and LASSO Cox regression were used to characterize risk factors. The Cox model was conducted to develop a Clinic-PET nomogram to predict the relapse status in the training set (n = 171). The nomogram's performance was estimated through discrimination, calibration, and clinical utility. The prognostic prediction model was validated in the test set (n = 63). RESULTS: Eight radiomics features were selected to assess the radiomics score (radscore) of the operation side (Lat_radscore) and the asymmetric index (AI) of the radiomics score (AI_radscore). AI_radscor, Lat_radscor, secondarily generalized seizures (SGS), and duration between seizure onset and surgery (Durmon) were significant predictors of seizure-free outcomes. The final model had a C-index of 0.68 (95 %CI: 0.59-0.77) for complete freedom from seizures and time-dependent AUROC was 0.65 at 12 months, 0.65 at 36 months, and 0.59 at 60 months in the test set. A web application derived from the primary predictive model was displayed for economic and efficient use. CONCLUSIONS: A PET-based radiomics nomogram is clinically promising for predicting seizure outcomes after temporal lobe epilepsy surgery.

Anion-Coordination Foldamer-Based Polymer Network: from Molecular Spring to Elastomer.

Foldamer is a scaled-down version of coil spring, which can absorb and release energy by conformational change. Here, polymer networks with high density of molecular springs were developed by employing anion-coordination-based foldamers as the monomer. The coiling of the foldamer is controlled by oligo(urea) ligands coordinating to chloride ions; subsequently, the folding and unfolding of foldamer conformations endow the polymer network with excellent energy dissipation and toughness. The mechanical performance of the corresponding polymer networks shows a dramatic increase from P-L2UCl (non-folding), to P-L4UCl (a full turn), and then to P-L6UCl (1.5 turns), in terms of strength (2.62 MPa; 14.26 MPa; 22.93 MPa), elongation at break (70 %; 325 %; 352 %), Young's modulus (2.69 MPa; 63.61 MPa; 141.50 MPa), and toughness (1.12 MJ/m3; 21.39 MJ/m3; 49.62 MJ/m3), respectively, which is also better than those without anion centers and the non-foldamer based counterparts. Moreover, P-L6UCl shows enhanced strength and toughness than most of the molecular-spring based polymer networks. Thus, an effective strategy for designing high-performance anion-coordination-based materials is presented.

Monitoring hepatocellular carcinoma using tumor content in circulating cell-free DNA.

PURPOSE: To evaluate the utility of tumor content in circulating cell-free DNA (ccfDNA) for monitoring hepatocellular carcinoma (HCC) throughout its natural history. METHODS: We included 67 hepatitis B virus (HBV)-related HCC patients, of whom 17 had paired pre- and post-treatment samples, and 90 controls. Additionally, in a prospective cohort with HBV surface antigen-positive participants recruited in 2012 and followed up biannually with blood sample collections until 2019, we included 270 repeated samples before diagnosis from 63 participants who later developed HCC (pre-HCC samples). Shallow whole-genome sequencing and the ichorCNA method were used to analyze genome-wide copy number and tumor content in ccfDNA. RESULTS: High tumor content was associated with advanced tumor stage (P < 0.001) and a poor survival after HCC diagnosis (HR=12.35; 95% confidence interval [CI]=1.413-107.9; P = 0.023). Tumor content turned negative after surgery (P = 0.027), while remained positive after transarterial chemoembolization treatment (P = 0.578). In non-HCC samples, the mean tumor content (±SD) was 0.011 (±0.007) and had a specificity of 97.8% (95%CI=92.2%-99.7%). In pre-HCC samples, tumor content increased from 0.014 in 4 years before diagnosis to 0.026 in 1 year before diagnosis. The sensitivity of tumor content in detecting HCC increased from 22.7% (95%CI=11.5%-37.8%) within one year before diagnosis to 30.4% (95%CI=13.2%-52.9%) at BCLC stage 0/A, 81.8% (95%CI=59.7%-94.8%) at stage B, and 95.5% (95%CI=77.2%-99.9%) at stage C. CONCLUSIONS: The tumor content in ccfDNA is correlated with tumor burden and may help in monitoring HCC one year earlier than clinical diagnosis and in predicting patient prognosis.

Peripheral Control of the Assembly and Chirality of Anion-Based Octanuclear Cubes by Cation-π Networks.

Self-assembly of sophisticated polyhedral cages has drawn much attention because of their elaborate structures and potential applications. Herein, we report the anion-coordination-driven assembly of the first A8L12 (A = anion, L = ligand) octanuclear cubic structures from phosphate anion and p-xylylene-spaced bis-bis(urea) ligands via peripheral templating of countercations (TEA+ or TPA+). By attaching terminal aryl rings (phenyl or naphthyl) to the ligand through a flexible (methylene) linker, these aryls actively participate in the formation of plenty of "aromatic pockets" for guest cation binding. As a result, multiple peripheral guests (up to 22) of suitable size are bound on the faces and vertices of the cube, forming a network of cation-π interactions to stabilize the cube structure. More interestingly, when chiral ligands were used, either diastereomers of mixed Λ- and Δ-configurations (with TEA+ countercation) for the phosphate coordination centers or enantiopure cubes (with TPA+) were formed. Thus, the assembly and chirality of the cube can be modulated by remote terminal groups and peripheral templating tetraalkylammonium cations.

Machine learning techniques based on 18F-FDG PET radiomics features of temporal regions for the classification of temporal lobe epilepsy patients from healthy controls.

Background: This study aimed to investigate the clinical application of 18F-FDG PET radiomics features for temporal lobe epilepsy and to create PET radiomics-based machine learning models for differentiating temporal lobe epilepsy (TLE) patients from healthy controls. Methods: A total of 347 subjects who underwent 18F-FDG PET scans from March 2014 to January 2020 (234 TLE patients: 25.50 ± 8.89 years, 141 male patients and 93 female patients; and 113 controls: 27.59 ± 6.94 years, 48 male individuals and 65 female individuals) were allocated to the training (n = 248) and test (n = 99) sets. All 3D PET images were registered to the Montreal Neurological Institute template. PyRadiomics was used to extract radiomics features from the temporal regions segmented according to the Automated Anatomical Labeling (AAL) atlas. The least absolute shrinkage and selection operator (LASSO) and Boruta algorithms were applied to select the radiomics features significantly associated with TLE. Eleven machine-learning algorithms were used to establish models and to select the best model in the training set. Results: The final radiomics features (n = 7) used for model training were selected through the combinations of the LASSO and the Boruta algorithms with cross-validation. All data were randomly divided into a training set (n = 248) and a testing set (n = 99). Among 11 machine-learning algorithms, the logistic regression (AUC 0.984, F1-Score 0.959) model performed the best in the training set. Then, we deployed the corresponding online website version (https://wane199.shinyapps.io/TLE_Classification/), showing the details of the LR model for convenience. The AUCs of the tuned logistic regression model in the training and test sets were 0.981 and 0.957, respectively. Furthermore, the calibration curves demonstrated satisfactory alignment (visually assessed) for identifying the TLE patients. Conclusion: The radiomics model from temporal regions can be a potential method for distinguishing TLE. Machine learning-based diagnosis of TLE from preoperative FDG PET images could serve as a useful preoperative diagnostic tool.

Study on dynamic characteristics of salinized silt under cyclic loading.

Under the repeated action of aircraft taxiing load, the subgrade plastic deformation becomes the key factor affecting the service performance of the airfields when salinized silt is used to fill the subgrade. In this study, the dynamic triaxial tests were carried out on a region in the northern part of China to study the effects of different salt contents on the dynamic characteristics of silt under cyclic loading. A prediction model for the salinized silt dynamic strength with a plastic strain of 4% as the failure criterion for the subgrade was thus proposed. It is found that with the increase of dynamic stress amplitude, the salinized silt plastic deformation transforms gradually from plastic deformation to incremental failure. The salt contents significantly influence the plastic strain and critical dynamic stress of silt. The strength of the salinized silt specimen is related to the ion concentration in the soil pores and the arrangement pattern of soil particles, as indicated by the progressive strength increase of the salinized silt at the low salt content of 1% and a further gradual decrease at high salt content.

A comparative study on the transbrachial and transfemoral approaches for the treatment of superior mesenteric artery lesions.

BACKGROUND: Superior Mesenteric Artery (SMA) lesions present a significant challenge in endovascular surgery. Both the transbrachial (TBA) and the transfemoral (TFA) approaches have been employed for the treatment of these lesions, but the comparative effectiveness of these methods remains unclear. MATERIALS AND METHODS: A retrospective analysis was conducted on patients who underwent TBA and TFA at a tertiary center between June 2020 and February 2023. Key parameters including technical success, procedural details, and complication rates were examined. RESULTS: In a study of 99 patients, 66 underwent Transfemoral Approach (TFA) and 33 underwent Transbrachial Approach (TBA). No significant age or gender differences were noted between groups. TFA procedures were longer (90.0 vs 63.5 min, p = 0.002) and had higher fluoroscopy times (59.0 vs 43.0 min, p = 0.02) and selective SMA times (366.0 vs 245.0 min, p = 0.038) compared to TBA, especially with a smaller aortomesenteric angle (<90°). Technical success rates were high in both groups (TFA 97%, TBA 93.9%, p = 0.60). Complication rates were similar between groups, with no significant predictors for access site complications identified. CONCLUSION: Both the TBA and the TFA are effective for the treatment of SMA lesions, with TBA potentially offering advantages in terms of efficiency and patient recovery, particularly in cases with certain anatomy. No significant differences in complication rates were found between the two groups. Further research, including prospective randomized trials, is needed to confirm these findings.

Sirtuin 4 (Sirt4) downregulation contributes to chondrocyte senescence and osteoarthritis via mediating mitochondrial dysfunction.

Chondrocyte senescence has recently been proposed as a key pathogenic mechanism in the etiology of osteoarthritis (OA). Nevertheless, the precise molecular mechanisms underlying chondrocyte senescence remain poorly understood. To address this knowledge gap, we conducted an investigation into the involvement of Sirtuin 4 (Sirt4) in chondrocyte senescence. Our experimental findings revealed a downregulation of Sirt4 expression in TBHP-induced senescent chondrocytes in vitro, as well as in mouse OA cartilage. Additionally, we observed that the knockdown of Sirt4 in chondrocytes promoted cellular senescence and cartilage degradation, while the overexpression of Sirt4 protected the cells against TBHP-mediated senescence of chondrocytes and cartilage degradation. Moreover, our findings revealed elevated levels of reactive oxygen species (ROS), abnormal mitochondrial morphology, compromised mitochondrial membrane potential, and reduced ATP production in Sirt4 knockdown chondrocytes, indicative of mitochondrial dysfunction. Conversely, Sirt4 overexpression successfully mitigated TBHP-induced mitochondrial dysfunction. Further analysis revealed that Sirt4 downregulation impaired the cellular capacity to eliminate damaged mitochondria by inhibiting Pink1 in chondrocytes, thereby enhancing the accumulation of ROS and facilitating chondrocyte senescence. Notably, the overexpression of Pink1 counteracted the effects of Sirt4 knockdown on mitochondrial dysfunction. Importantly, our study demonstrated the promise of gene therapy employing a lentiviral vector encoding mouse Sirt4, as it successfully preserved the integrity of articular cartilage in mouse models of OA. In conclusion, our findings provide compelling evidence that the overexpression of Sirt4 enhances mitophagy, restores mitochondrial function, and protects against chondrocyte senescence, thereby offering a novel therapeutic target and potential strategy for the treatment of OA.

Characterization of Eighty-Eight Single-Nucleotide Polymorphism Markers in the Manila Clam Ruditapes philippinarum Based on High-Resolution Melting (HRM) Analysis.

Single-nucleotide polymorphisms (SNPs) are the most commonly used DNA markers in population genetic studies. We used the Illumina HiSeq4000 platform to develop single-nucleotide polymorphism (SNP) markers for Manila clam Ruditapes philippinarum using restriction site-associated DNA sequencing (RAD-seq) genotyping. Eighty-eight SNP markers were successfully developed by using high-resolution melting (HRM) analysis, with a success rate of 44%. SNP markers were analyzed for genetic diversity in two clam populations. The observed heterozygosity per locus ranged from 0 to 0.9515, while the expected heterozygosity per locus ranged from 0.0629 to 0.4997. The value of FIS was estimated to be from -0.9643 to 1.0000. The global Fst value was 0.1248 (p < 0.001). After Bonferroni correction, 15 loci deviated significantly from the Hardy-Weinberg equilibrium (p < 0.0006). These SNP markers provide a valuable resource for population and conservation genetics studies in this commercially important species.

Assessment of whole-body and regional body fat using abdominal quantitative computed tomography in Chinese women and men.

BACKGROUND: Being overweight or obese has become a serious public health concern, and accurate assessment of body composition is particularly important. More precise indicators of body fat composition include visceral adipose tissue (VAT) mass and total body fat percentage (TBF%). Study objectives included examining the relationships between abdominal fat mass, measured by quantitative computed tomography (QCT), and the whole-body and regional fat masses, measured by dual energy X-ray absorptiometry (DXA), as well as to derive equations for the prediction of TBF% using data obtained from multiple QCT slices. METHODS: Whole-body and regional fat percentage were quantified using DXA in Chinese males (n = 68) and females (n = 71) between the ages of 24 and 88. All the participants also underwent abdominal QCT measurement, and their VAT mass and visceral fat volume (VFV) were assessed using QCT and DXA, respectively. RESULTS: DXA-derived TBF% closely correlated with QCT abdominal fat percentage (r = 0.89-0.93 in men and 0.76-0.88 in women). Stepwise regression showed that single-slice QCT data were the best predictors of DXA-derived TBF%, DXA android fat percentage and DXA gynoid fat percentage. Cross-validation analysis showed that TBF% and android fat percentage could be accurately predicted using QCT data in both sexes. There were close correlations between QCT-derived and DXA-derived VFV (r = 0.97 in men and 0.93 in women). CONCLUSION: Clinicians can assess the TBF% and android and gynoid fat percentages of Chinese women and men by analysing existing abdominal CT-derived data using the QCT technique.

Incorporation of an Anion-Coordinated Triple Helicate into a Thin Film for Choline Recognition in an Aqueous System.

Functional thin films, being fabricated by incorporating discrete supramolecular architectures, have potential applications in research areas such as sensing, energy storage, catalysis, and optoelectronics. Here, we have determined that an anion-coordinated triple helicate can be solution-processed into a functional thin film by incorporation into a polymethyl methacrylate (PMMA) matrix. The thin films fabricated by the incorporation of the anion-coordinated triple helicate show multiple optical properties, such as fluorescence, CD, and CPL. In addition, the film has the ability to recognize choline and choline derivatives in a water system. The successful recognition of Ch+ by the film represents the first example of utilizing 'aniono'-supramolecular architectures for biomolecule detection in aqueous solution and opens up a new route for designing biocompatible functional materials.

Klf10 is involved in extracellular matrix calcification of chondrocytes alleviating chondrocyte senescence.

Osteoarthritis (OA) is a chronic degenerative disease resulting joint disability and pain. Accumulating evidences suggest that chondrocyte extracellular matrix calcification plays an important role in the development of OA. Here, we showed that Krüppel-like factor 10 (Klf10) was involved in the regulation of chondrocyte extracellular matrix calcification by regulating the expression of Frizzled9. Knockdown of Klf10 attenuated TBHP induced calcification and reduced calcium content in chondrocytes. Restoring extracellular matrix calcification of chondrocytes could aggravate chondrocyte senescence. Destabilization of a medial meniscus (DMM) mouse model of OA, in vivo experiments revealed that knockdown Klf10 improved the calcification of articular cartilage and ameliorated articular cartilage degeneration. These findings suggested that knockdown Klf10 inhibited extracellular matrix calcification-related changes in chondrocytes and alleviated chondrocyte senescence.

Combined ATAC-seq, RNA-seq, and GWAS analysis reveals glycogen metabolism regulatory network in Jinjiang oyster ( Crassostrea ariakensis).

Glycogen serves as the principal energy reserve for metabolic processes in aquatic shellfish and substantially contributes to the flavor and quality of oysters. The Jinjiang oyster ( Crassostrea ariakensis) is an economically and ecologically important species in China. In the present study, RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin using sequencing (ATAC-seq) were performed to investigate gene expression and chromatin accessibility variations in oysters with different glycogen contents. Analysis identified 9 483 differentially expressed genes (DEGs) and 7 215 genes with significantly differential chromatin accessibility (DCAGs) were obtained, with an overlap of 2 600 genes between them. Notably, a significant proportion of these genes were enriched in pathways related to glycogen metabolism, including "Glycogen metabolic process" and "Starch and sucrose metabolism". In addition, genome-wide association study (GWAS) identified 526 single nucleotide polymorphism (SNP) loci associated with glycogen content. These loci corresponded to 241 genes, 63 of which were categorized as both DEGs and DCAGs. This study enriches basic research data and provides insights into the molecular mechanisms underlying the regulation of glycogen metabolism in C. ariakensis.

One-Electron (2c/1e) Tin···Tin Bond Stabilized by ortho-Phenylenediamido Ligands.

Odd-electron bonds, i.e., the two-center, three-electron (2c/3e), or one-electron (2c/1e) bonds, have attracted tremendous interest owing to their novel bonding nature and radical properties. Herein, complex [K(THF)6][LSn:···Sn:L] (1), featuring the first and unsupported 2c/1e Sn···Sn σ-bond with a long distance (3.2155(9) Å), was synthesized by reduction of stannylene [LSn:] (L = N,N-dpp-o-phenylene diamide) with KC8. The one-electron Sn-Sn bond in 1 was confirmed by the crystal structure, DFT calculations, EPR spectroscopy, and reactivity studies. This compound can be viewed as a stabilized radical by delocalizing to two metal centers and can readily mediate radical reactions such as C-C coupling of benzaldehyde.

Molecular mechanism of WWP1-mediated ubiquitination modification affecting proliferation and invasion/migration of liver cancer cells.

Liver cancer is the most prevalent fatal malignancy across the globe. The present study aims to explore the molecular mechanism of E3 ligase WWP1 in liver cancer cell proliferation and invasion/migration. RT-qPCR and Western blot were performed to detect WWP1, KLF14, and VEPH1 expressions in liver cancer cell lines. Furthermore, WWP1 expression was silenced in cells, followed by the detection of cell viability, proliferation, and invasion/migration by CCK-8, colony formation, and Transwell assays, respectively. ChIP was used to analyze the binding relationship between WWP1 and KLF14. We measured the KLF14 ubiquitination level and KLF14 enrichment on the VEPH1 promoter after MG132 treatment. Dual-luciferase reporter assay was used to validate the binding relationship between KLF14 and VEPH1. Consequently, WWP1 was highly expressed in liver cancer cells; WWP1 silencing reduced the proliferation and invasion/migration of liver cancer cells. Mechanistically, WWP1 promoted KLF14 ubiquitination degradation; KLF14 was enriched on the VEPH1 promoter to promote its transcription and protein expression. Inhibiting KLF14 or VEPH1 partially minimized the inhibitory effect of WWP1 silencing on liver cancer cell proliferation and invasion/migration. In summary, WWP1 degrades KLF14 through ubiquitination, hence repressing VEPH1 expression and accelerating proliferation and invasion/migration of liver cancer cells.

Cerebrospinal fluid circulating tumor DNA contributes to the detection and characterization of leptomeningeal metastasis in non-small cell lung cancer.

PURPOSE: Cerebrospinal fluid (CSF) has revealed the unique genetic characteristics of leptomeningeal metastasis (LM) from non-small cell lung cancer (NSCLC). However, the research in this area is still very limited. METHODS: Patients with LM from NSCLC (n = 80) were retrospectively analyzed. Circulating tumor DNA (ctDNA) in CSF was tested by next-generation sequencing (NGS), with paired extracranial tissue or plasma samples included for comparison. An independent non-LM cohort (n = 100) was also analyzed for comparative purposes. Clinical outcomes were compared with Kaplan-Meier log-rank test and Cox proportional hazards methodologies. RESULTS: An overwhelming 93.8% of patients carried druggable mutations in NSCLC LM, with EGFR (78.8%) being the most prevalent. Notably, 4 patients who tested negative for driver genes in extracranial samples surprisingly showed EGFR mutations in their CSF and subsequently benefited from targeted therapy. There was a clear difference in genetic profiles between CSF and extracranial samples, with CSF showing more driver gene detections, increased Copy Number Variations (CNVs), and varied resistance mechanisms among individuals. Abnormalities in cell-cycle regulatory molecules were highly enriched in LM (50.9% vs 31.0%, p = 0.017), and CDKN2A/2B deletions were identified as an independent poor prognostic factor for LM patients, with a significant reduction in median OS (p = 0.013), supported by multivariate analysis (HR 2.63, 95% CI 1.32-5.26, p = 0.006). CONCLUSIONS: CSF-based ctDNA analysis is crucial for detecting and characterizing genetic alterations in NSCLC LM. The distinct genetic profiles in CSF and extracranial tissues emphasize the need for personalized treatment approaches.

Predictive value of metabolic parameters derived from preoperative 18F-FDG positron emission tomography/computed tomography for brain metastases in patients with surgically resected non-small cell lung cancer.

Background: Brain metastases (BMs) are common complications in patients with non-small cell lung cancer (NSCLC). The purpose of this study was to investigate whether the metabolic parameters derived from preoperative 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) can predict BM development in patients with surgically resected NSCLC. Methods: We retrospectively reviewed 128 consecutive patients with stage I-IIIA NSCLC who underwent 18F-FDG PET/CT before curative surgery at The First Affiliated Hospital of Jinan University between November 2012 and October 2021. By drawing a volume of interest (VOI), the maximum standardized uptake values (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumor as well as the mean SUV (SUVmean) of the liver and arterial blood were measured. The tumor-to-liver SUV ratio (TLR) and tumor-to-blood SUV ratio (TBR) were also calculated. Receiver operating characteristic curve analysis was used to determine the best cut-off values for positron emission tomography (PET) parameters to predict BM-free survival, and Cox proportional hazards regression analysis was used to assess the predictive value of clinical variables and PET parameters. Results: The median follow-up duration for survival patients was 23.4 months, and 15 patients (11.7%) experienced BM as the initial relapse site. The cumulative rates of BM over the course of 1, 2, and 5 years were 4.5%, 10.5%, and 17.5%, respectively. The optimal cut-off values for the prediction of BM-free survival were 7.7, 4.9, and 4.5 for SUVmax, TLR, and TBR, and 5.5 mL and 16.1 for MTV and TLG, respectively. In the Cox proportional hazards model, the risk of BM was significantly associated with TLR [hazard ratio (HR) =10.712; 95% confidence interval (CI): 2.958-38.801; P<0.001] and MTV (HR =3.150; 95% CI: 0.964-10.293; P=0.020) after adjusting for tumor stage, clinicopathological factors, and other PET parameters. Conclusions: Preoperative TLR and MTV of the primary tumor may be helpful in predicting BM development in patients with surgically resected NSCLC. Tumor metabolic parameters may potentially be used to stratify the risk of BM and determine individualized surveillance strategies.