Imaging the Meissner effect in hydride superconductors using quantum sensors.

By directly altering microscopic interactions, pressure provides a powerful tuning knob for the exploration of condensed phases and geophysical phenomena1. The megabar regime represents an interesting frontier, in which recent discoveries include high-temperature superconductors, as well as structural and valence phase transitions2-6. However, at such high pressures, many conventional measurement techniques fail. Here we demonstrate the ability to perform local magnetometry inside a diamond anvil cell with sub-micron spatial resolution at megabar pressures. Our approach uses a shallow layer of nitrogen-vacancy colour centres implanted directly within the anvil7-9; crucially, we choose a crystal cut compatible with the intrinsic symmetries of the nitrogen-vacancy centre to enable functionality at megabar pressures. We apply our technique to characterize a recently discovered hydride superconductor, CeH9 (ref. 10). By performing simultaneous magnetometry and electrical transport measurements, we observe the dual signatures of superconductivity: diamagnetism characteristic of the Meissner effect and a sharp drop of the resistance to near zero. By locally mapping both the diamagnetic response and flux trapping, we directly image the geometry of superconducting regions, showing marked inhomogeneities at the micron scale. Our work brings quantum sensing to the megabar frontier and enables the closed-loop optimization of superhydride materials synthesis.

Sub-region based radiomics analysis for prediction of isocitrate dehydrogenase and telomerase reverse transcriptase promoter mutations in diffuse gliomas.

AIM: To enhance the prediction of mutation status of isocitrate dehydrogenase (IDH) and telomerase reverse transcriptase (TERT) promoter, which are crucial for glioma prognostication and therapeutic decision-making, via sub-regional radiomics analysis based on multiparametric magnetic resonance imaging (MRI). MATERIALS AND METHODS: A retrospective study was conducted on 401 participants with adult-type diffuse gliomas. Employing the K-means algorithm, tumours were clustered into two to four subregions. Sub-regional radiomics features were extracted and selected using the Mann-Whitney U-test, Pearson correlation analysis, and least absolute shrinkage and selection operator, forming the basis for predictive models. The performance of model combinations of different sub-regional features and classifiers (including logistic regression, support vector machines, K-nearest neighbour, light gradient boosting machine, and multilayer perceptron) was evaluated using an external test set. RESULTS: The models demonstrated high predictive performance, with area under the receiver operating characteristic curve (AUC) values ranging from 0.918 to 0.994 in the training set for IDH mutation prediction and from 0.758 to 0.939 for TERT promoter mutation prediction. In the external test sets, the two-cluster radiomics features and the logistic regression model yielded the highest prediction for IDH mutation, resulting in an AUC of 0.905. Additionally, the most effective predictive performance with an AUC of 0.803 was achieved using the four-cluster radiomics features and the support vector machine model, specifically for TERT promoter mutation prediction. CONCLUSION: The present study underscores the potential of sub-regional radiomics analysis in predicting IDH and TERT promoter mutations in glioma patients. These models have the capacity to refine preoperative glioma diagnosis and contribute to personalised therapeutic interventions for patients.

[Investigation of the immune profile of multiple myeloma patients achieving long-term survival after autologous stem cell transplantation].

Objective: To identify the characteristics of the bone marrow immune microenvironment associated with long-term survival in multiple myeloma (MM) patients. Methods: In the follow-up cohort of patients with newly diagnosed MM and who received "novel agent induction therapy and subsequent autologous stem cell transplantation and immunomodulator maintenance therapy" in the First Affiliated Hospital of Sun Yat-sen University, a cross-sectional study was carried out between August 2019 and May 2020. Using NanoString technology, the RNA expression of 770 bone marrow immune-related markers was compared between 16 patients who had progression-free survival ≥5 years and 5 patients with progressive disease. Among the 16 patients who achieved long-term survival, 9 achieved persistent minimal residual disease (MRD) negative while the other 7 had persistent positive MRD. The functional scores of each kind of immune cells were calculated based on the expression level of characteristic genes, so as to indirectly obtained the proportion of each immune cell subset. The Mann-Whitney U test and the Kruskal Wallis test were used for statistical analysis. Results: The proportion of neutrophils was significantly higher in long-surviving MM patients than in patients with progressive disease [functional scores, 13.61 (13.33, 14.25) vs. 12.93 (12.58, 13.38); Z=2.31, P=0.021]. Among long-surviving patients, those who were MRD-positive had a significantly greater number of mast cells compared with those who were MRD-negative [functional scores, 7.09 (6.49, 8.57) vs. 6.03 (5.18, 6.69); H=2.18, P=0.029]. Compared with patients with progressive disease, four genes (CTSG, IFIT2, S100B, and CHIT1) were significantly downregulated and six (C4B, TNFRSF17, CD70, IRF4, C2, and GAGE1) were upregulated in long-surviving patients. Among long-surviving patients, only gene CMA1 was significantly upgraded, 10 genes (ISG15, OAS3, MX1, IFIT2, DDX58, SIGLEC1, CXCL10, IL1RN, SERPING and TNFSF10) were significantly downregulated in the MRD-positive group compared with that in the MRD-negative group, the first 5 of which are related to the interferon response pathway. Conclusions: The increased neutrophil and mast cell numbers may be related to long-term survival in MM. Interferon signaling activation may be a key bone marrow immune profiling feature for MRD-negative, long-surviving patients with MM.

[Application value of folate receptor-positive circulating tumor cells in the diagnosis of head and neck squamous cell carcinoma].

A total of 82 patients and healthy subjects in the First Affiliated Hospital of Sun Yat-sen University from March to August 2023 were recruited. The cohort consisted of 43 patients with head and neck squamous cell carcinoma (HNSCC) and 39 non-cancer patients or healthy subjects. There were 63 males and 19 females, with a median age of 62 (46, 67) years. The levels of folate receptor-positive circulating tumor cells (FR+CTCs) in the blood of HNSCC patients and non-cancer/healthy subjects were 12.4 (8.5, 17.8) floate unit (FU)/3 ml and 5.0 (3.8, 6.6) FU/3 ml, respectively, with a statistically significant difference (P<0.001). The area under the receiver operating characteristic (ROC) curve for FR+CTCs levels was 0.937 (95%CI: 0.888-0.986, P<0.001), with a cut-off value of 7.4 FU/3 ml determined by the maximum Youden index. At this cut-off value, the sensitivity and specificity of FR+CTCs for diagnosing HNSCC were 90.70% and 89.74%, respectively. The current study suggests that FR+CTCs could be used as a liquid biopsy marker for the screening and diagnosis of HNSCC.

[Clinicopathological features of metastatic melanoma in effusion cytology of serosal cavity].

Objective: To investigate the clinical, cytomorphology, immunocytochemical and molecular features of metastatic melanoma in serosal cavity effusion. Methods: Cytological specimens of 14 patients with melanoma in the chest and abdomen were collected from 2017 to 2023, at the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. SOX10, S-100 protein, PRAME, BRAF V600E, HMB45, and Melan A were detected by immunocytochemical methods. Fourteen cases were tested for routine antibody combinations, including Claudin4, HEG1, Calretinin, CD68, etc. Four of the patients had biopsy or surgical samples of metastatic solid lesions of primary sites, and further next-generation sequencing (NGS) or amplification refractory mutation system (ARMS)-PCR molecular test was performed. In addition, 30 cases of serosal effusion samples were collected as control groups (10 cases of benign mesothelial cell reactive hyperplasia, 10 cases of mesothelioma, and 10 cases of metastatic lung adenocarcinoma). Results: Among the 14 cases of melanoma, there were 7 males and 7 females, with ages ranging from 35 to 86 years, and an average age of 57 years, there 10 cases aged ≥50 years. The tumor cells in the serosal effusion varied in morphology and degree of atypia. SOX10 was positive in all 14 cases (14/14), S-100 protein was positive in 10 cases (10/14), PRAME was positive in 12 cases (12/14), BRAF V600E was positive in 10 cases (10/14), HMB45 was positive in 12 cases (12/14), and Melan A was positive in 13 cases (13/14). In 4 patients with histological correlation, the cytological and histological expression of SOX10, BRAF V600E, and PRAME was positive in all 4 cases (4/4); S-100 protein was positive in 2 cases (2/4); and HMB45 and Melan A were positive in 3 cases (3/4). Using NGS or ARMS-PCR, missense mutations of BRAF V600E were detected in all 4 patients; TERT promoter mutations was detected in 1 case; and CDKN2A terminating mutations and MSI1 deletion mutations were detected in the other case. SOX10, S-100, HMB45, Melan A, PRAME and BRAF V600E were all negative in 30 control samples of serosal cavity effusion. Conclusion: By observing the morphology of tumor cells, immunocytochemical test of several combination markers, especially the expression of SOX10, BRAF V600E and PRAME, can help to improve the positive diagnosis rate of melanoma in serous cavity effusion.

[Prognostic performance of pulmonary effective arterial elastance in patients with heart failure].

Objective: To explore the predictive value of pulmonary effective arterial elastance (Ea) in patients with heart failure (HF). Methods: This is a retrospective cohort study, which retrospectively included 284 patients with HF who underwent right heart catheterization at Heart Failure Center in Fuwai Hospital between September 2013 and February 2022. Data regarding baseline clinical characteristics, hemodynamic profiles, and prognosis were collected. Ea was calculated as mean pulmonary arterial pressure/stroke volume. Patients were divided into Ea<0.555 group and Ea≥0.555 group according to the median value of Ea (0.555 mmHg/ml, 1 mmHg=0.133 kPa). The primary outcome was the primary clinical event, set as the first occurrence of a series of composite events, including all-cause death, heart transplantation, left ventricular assist device implantation, and HF rehospitalization. Event-free survival was defined as the absence of primary clinical events. Spearman correlation analysis was used to calculate the correlation coefficient between Ea and parameters reflective of right heart function. The Kaplan-Meier analysis was used to compare the different groups for the estimation of outcomes with the log-rank test. We used Cox proportional-hazards regression models to estimate hazard ratios (HR) for primary clinical event. Subgroup analysis was performed based on the age, gender, New York Heart Association (NYHA) functional class, left ventricular ejection fraction, presence of pulmonary hypertension, and serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) values. We used receiver operating characteristic (ROC) curve to calculate the area under the curve (AUC) of Ea for predicting event-free survival in patients with HF. Results: The median age was 51 years, and 206 (72.5%) patients were male. Ea and pulmonary vascular resistance (PVR) were significantly correlated (r=0.698, P<0.001). The correlation between Ea and pulmonary arterial elastance (PAC) were even more significant (r=-0.888, P<0.001). Compared with Ea<0.555 group, Ea≥0.555 group presented with higher serum NT-proBNP values (4 443 (1 792, 8 554) ng/L vs. 1 721 (480, 4 528)ng/L,P<0.001), higher PVR (3.4 (2.5, 4.7) Wood vs. 1.4 (0.9, 2.2) Wood, P<0.001), lower cardiac output (3.0 (2.3, 3.9) L/min vs. 4.3 (3.8, 4.9) L/min, P<0.001), and lower PAC (1.6 (1.3, 2.0) ml/mmHg vs. 4.0 (3.0, 6.0) ml/mmHg, P<0.001). The median follow-up time was 392 (166, 811) days. The Kaplan-Meier survival curve demonstrated a lower event-free survival rate in the Ea≥0.555 group compared to the Ea<0.555 group (Plog-rank<0.001). After multivariate adjustment, Ea (HR=1.734, P<0.001) remained significantly associated with the primary outcome. Subgroup analysis indicated that Ea was associated with the primary outcome across all subgroups. The AUC was 0.724 (P<0.001) for Ea to predict event-free survival calculated from ROC analysis. Conclusions: Ea is closely related to parameters reflective of right ventricular afterload. Increased Ea is an independent predictor of adverse outcomes in patients with HF.

[The efficacy analysis of neurosurgical robot-assisted DBS in the treatment of elderly Parkinson's disease].

Objective: To investigate the surgical efficacy of neurosurgery robot deep brain stimulation(DBS) in the treatment of elderly Parkinson's disease(PD). Methods: The clinical data of elderly patients (≥75 years) with PD who underwent neurosurgical robot-assisted DBS surgery in the Department of Neurosurgery of the General Hospital of Northern Theater Command from September 2016 to September 2022 were collected retrospectively. Operation time, electrode implantation duration, postoperative pneumocephalus volume, electrode implantation accuracy, the Tao's DBS surgery scale, perioperative complications were analyzed.The unified Parkinson's disease rating scales (UPDRS), UPDRS-Ⅲ, tremor, rigidity, bradykinesia, axial, Barthel Activities of Daily Living (ADL-Barthel), Levodopa Equivalent Daily Dose (LEDD), Montreal Cognitive Assessment (MoCA), Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) scores and mortality were assessed respectively before operation, 6, 12 and 24 months after operation and last follow-up. Results: A total of 25 elderly patients were enrolled, including 14 males and 11 females, aged(78.3±3.2) years. Nine patients had underlying diseases. Nine patients (36%) underwent bilateral Globus Pallidus pars Interna deep brain stimulation (GPi-DBS) and 16 patients (64%) underwent bilateral subthalamic nucleus deep brain stimulation (STN-DBS).The operation time was (1.56±0.19) hours, the electrode implantation duration was (1.01±0.19) hours, the pneumocephalus volume was 9.8(4.7, 23.3) cm3, and the electrode implantation accuracy was (0.84±0.24) mm, the Tao's DBS surgery scale was (80.2±6.2).The follow-up time [M(Q1, Q3)] was 57.3(27.9, 75.7) months. No serious complications such as intracranial hemorrhage, infection or poor wound healing occurred during the perioperative period. The improvement rate of UPDRS, UPDRS-Ⅲ, rigidity, bradykinesia, and LEDD at 6 months after surgery was significantly higher than that at 24 months after surgery and at the last follow-up (all P<0.05); the improvement rate of axial symptoms, ADL-Barthel score, and MoCA score at 6 months after surgery was significantly higher than that at the last follow-up (P<0.05). HAMD and HAMA scores showed no significant improvement during follow-up after surgery (both P>0.05). At the last follow-up, 12 patients died, with death time of (35.1±20.2) months after operation, and the death age of [M(Q1, Q3)] 80(79, 83)years. Conclusions: Robot-assisted DBS surgery for elderly patients with PD is accurate and safe, and the postoperative symptoms are significantly improved, and they can benefit from neuromodulation for long term, and the risks are controllable.

[Overexpression of LncRNA MEG3 promotes ferroptosis and enhances chemotherapy sensitivity of hepatocellular carcinoma cells to cisplatin].

OBJECTIVE: To investigate the effect of overexpression of LncRNA MEG3 on proliferation, migration and cisplatin sensitivity of hepatoma cells HepG2 and LM3 and explore the underlying and mechanism. METHODS: The expression of MEG3 in healthy individuals and patients with hepatocellular carcinoma (HCC) was analyzed by online bioinformatics analysis, and Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect MEG3 expression in different HCC cell lines. A MEG3-overexpresing plasmid was transfected in HepG2 and LM3 cells, and the changes in cell proliferation and migration were examined using CCK8 assay and scratch assay. CCK8 assay was used to determine the inhibitory rate of cisplatin on the transfected cells. A reactive oxygen species (ROS) fluorescence probe (DCFH-DA) and malondialdehyde (MDA) kit were used to assess the changes in ROS production and MDA level in the cells. Western blotting was performed to detect the expression levels of ferroptosis-related proteins glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1). RESULTS: The expression of MEG3 was significantly lower in HCC cells than in LO2 cells, which was consistent with the results of bioinformatic analysis (P < 0.05). Overexpression of MEG3 in the HCC cell lines significantly suppressed cell proliferation and migration (P < 0.05), increased the cell inhibition rate of cisplatin (P < 0.05), enhanced cellular ROS production and increased MDA levels in the cells (P < 0.05). MEG3 overexpression significantly decreased the expressions of GPX4 and FTH1 in the HCC cell lines. CONCLUSION: The expression of MEG3 is decreased in HCC cells, and its overexpression inhibits proliferation and migration and enhances cisplatin sensitivity of HCC cells by promoting ferroptosis of the cells.

Unveiling attenuation structures in the northern Taiwan volcanic zone.

This cutting-edge study delves into regional magmatism in northern Taiwan through advanced 3-D P- and S-wave frequency-dependent attenuation tomography. Positioned at the dynamic convergence boundary between the Philippine Sea Plate and the Eurasian Plate, Taiwan experiences moderate earthquakes and intriguing volcanic activity, with a focus on the Tatun volcano group. Employing the Formosa seismic array for high-resolution results, our research identifies high-attenuation anomalies (low Q) beneath the northern Taiwan volcanic zone (NTVZ) and offshore submarine volcanoes, indicative of potential hydrothermal activities and magma reservoirs at varying depths. Additionally, we explore low-attenuation anomalies (high Q) in the forearc region of the Ryukyu subduction zone, suggestive of partial saturation linked to serpentinization processes resulting from seawater infiltration or forearc mantle hydration. These findings shed light on the complex geological features and provide essential insights into the crustal properties of northern Taiwan, contributing to a deeper understanding of its magmatic evolution and tectonic processes.

Staging laparoscopy with peritoneal lavage to identify peritoneal metastases and free intraperitoneal cancer cells in the management of locally advanced gastric cancer.

INTRODUCTION: Gastric cancer often presents in advanced stage with a significant risk for peritoneal dissemination. Staging laparoscopy can be used to detect peritoneal carcinomatosis (PC+) and free cancer cells in peritoneal lavage cytology (CY+). The current study aimed to present the outcomes of staging laparoscopy and the prognosis of PC+ and CY+ in a Swedish high-volume center. MATERIALS AND METHODS: A cohort study including all consecutive patients with locally advanced gastric cancer who underwent staging laparoscopy between February 2008 and October 2022. The laparoscopy findings were categorized as PC+, PC-CY+ (positive cytology without peritoneal carcinomatosis) or negative laparoscopy (PC-CY-). The primary endpoint was overall survival (OS) stratified by laparoscopy findings. The secondary endpoint was OS within each laparoscopy finding group stratified by subsequent treatment. RESULTS: Among 168 patients who underwent staging laparoscopy, 78 patients (46%) had PC-CY-, 29 patients (17%) had PC-CY+ and 61 patients (36%) had PC+. Decreased OS was observed for both PC-CY+ patients (aHR 2.14, 95% CI 1.13-4.06) and PC+ patients (aHR 5.36, 95% CI 3.21-8.93), compared to PC-CY-. Patients with PC-CY+ who converted to PC-CY- after chemotherapy and underwent tumor resection seemed to have a better prognosis compared to patients with persisting PC-CY+. CONCLUSIONS: Staging laparoscopy is an important tool in the staging of locally advanced gastric cancer. Tumor resection for patients with PC-CY+ who convert to PC-CY- may lead to improved survival for these patients.

Identification and verification of feature biomarkers associated with immune cells in recurrent pregnancy loss.

OBJECTIVE: The aim of this study was to investigate the causes, diagnostic markers, and treatment methods for recurrent pregnancy loss (RPL) using bioinformatics approaches. MATERIALS AND METHODS: Bioinformatics methods were utilized to analyze gene expression databases to identify key genes and modules associated with RPL. Weighted gene co-expression network analysis (WGCNA) was employed to identify gene sets related to maternal-fetal immunity. Gene set variation analysis (GSVA) and protein-protein interaction networks were used to explore signaling pathways and molecular interactions in RPL. Immune cell infiltration was assessed using single-sample gene set enrichment analysis (ssGSEA). RESULTS: Thirteen genes were identified as potential diagnostic markers, some of which were involved in placental amino acid transport, glucose absorption, and reactive oxygen species production. Several gene sets related to protein transport, steroid synthesis, and glycosaminoglycan degradation were found to be associated with RPL. Immune cell infiltration analysis found that CD56bright NK cells and monocytes showed significantly increased infiltration in RPL and were associated with key hub genes. The validation of hub genes, including PCSK5, CCND2, SLC5A3, RASAL1, MYZAP, MFAP4, and P2RY14, as potential diagnostic markers, showed promising value. CONCLUSIONS: This study contributes to a better understanding of the etiology of RPL and potential diagnostic markers. The identified immune-related gene sets, signaling pathways, and immune cell infiltrations provide valuable insights for future research and therapeutic advancements in RPL.