Leptomeningeal spread in high-grade gliomas: Is surgery or adjuvant therapy after leptomeningeal spread associated with survival benefit?

PURPOSE: This study aimed to identify prognostic factors associated with survival in patients with high-grade glioma (HGG) after leptomeningeal spread (LMS) and to clarify the behavior and treatment response. METHODS: This retrospective study included 114 patients with HGGs diagnosed with LMS from August 1, 2014, to July 30, 2021, at our institution. Clinical, radiological, pathological, and outcome data were collected. Univariable and multivariable Cox regression were used for overall survival (OS) and post-LMS survival (PLS) analysis. RESULTS: The median OS was 17.0 months and the median PLS was 6.0 months. Gross total resection (GTR) after LMS diagnosis and pathology grade III were statistically significantly associated with longer OS in all patients. GTR after LMS diagnosis and nodular LMS were independent favorable prognostic factors on PLS. Non-adjuvant therapy after LMS diagnosis was associated with shorter OS and PLS. In glioblastoma (GBM) subgroup analysis, GTR after LMS diagnosis and secondary LMS were independent favorable prognostic factors on OS. Karnofsky Performance Status (KPS) of ≥80 at LMS diagnosis, chemotherapy after LMS and intrathecal methotrexate (MTX) treatment were statistically significantly associated with longer PLS. MRI type II was a predictor of shorter PLS. CONCLUSION: The treatment of patients with glioma after LMS diagnosis is very challenging and limited. Safe GTR of tumor and subsequent adjuvant therapy after LMS remains a powerful weapon to improve survival for HGG patients with LMS. Chemotherapy and Intrathecal MTX treatment are feasible treatments after LMS. The extent of tumor dissemination may affect the survival after LMS.

Total Ionizing Dose Effects on the Threshold Voltage of GaN Cascode Devices.

GaN devices are nowadays attracting global attention due to their outstanding performance in high voltage, high frequency, and anti-radiation ability. Research on total ionizing dose and annealing effects on E-mode GaN Cascode devices has been carried out. The Cascode device consists of a low-voltage MOSFET and a high-voltage depletion-mode GaN MISHEMT. Cascode devices of both conventional processed MOSFET and radiation-hardened MOSFET devices are fabricated to observe the TID effects. Experiment results indicate that, for the Cascode device with conventional processed MOSFET, the VTH shifts to negative values at 100 krad(Si). For the Cascode device with radiation-hardened MOSFET, the VTH shifts by -0.5 V at 100 krad(Si), while shifts to negative values are 500 krad(Si). The annealing process, after the TID experiment, shows that it can release trapped charges and help VTH recover. On one hand, the VTH shift and recover trends are similar to those of a single MOSFET device, suggesting that the MOSFET is the vulnerable part in the Cascode which determines the anti-TID ability of the device. On the other hand, the VTH shift amount of the Cascode device is much larger than that of a previously reported p-GaN HEMT device, indicating that GaN material shows a better anti-TID ability than Si.

Systematic Review and Meta-Analysis: Association between Preoperative Ustekinumab and Surgical Complications in Crohn's Disease Patients.

INTRODUCTION: The impact of ustekinumab (UST) therapy on surgical complications in patients with Crohn's disease (CD) remains controversial. The aim of this meta-analysis is to explore the link between these two. METHODS: Databases (PubMed, Web of Science, Cochrane, and Springer Link) were searched until April 2022. Studies of CD patients who received UST and no UST prior to surgery (including no biological therapy, anti-tumor necrosis factor-α [anti-TNF-α] agent, and vedolizumab [VDZ]) were included. Primary outcomes included overall complications, infectious complications, and noninfectious complications. RESULTS: Nine studies totaling 3,225 CD patients were enrolled; 332 patients received UST treatment. There was no evidence of difference in the overall complications (odds ratio [OR] = 0.84, p = 0.37, 95% confidence interval [CI] = [0.57-1.23], I2 = 40%) between CD patients who had UST treatment preoperatively and those who had no UST treatment. There was no evidence of a difference in infectious complications (OR = 1.15, p = 0.35, 95% CI = [0.86-1.53], I2 = 2%). Additionally, there was no significant evidence of difference between these groups in terms of noninfectious complications and death. Specifically, there was no evidence of difference in overall complications, infection complications (including wound complications, sepsis, abscess, and anastomotic leakage), and noninfection complications (ileus, readmission, and return to operation), compared with no biological therapy and anti-TNF-α agents. At the same time, no significant evidence of difference was discovered in the comparison of preoperative UST and VDZ therapy in terms of overall complications, infectious complications (sepsis and abscess), and noninfectious complications (intestinal obstruction, readmission, and recovery surgery). CONCLUSION: In general, compared with other biological agents, preoperative use of UST in the treatment of CD patients is usually safe and does not increase surgical complications.

A False Trigger-Strengthened and Area-Saving Power-Rail Clamp Circuit with High ESD Performance.

A power clamp circuit, which has good immunity to false trigger under fast power-on conditions with a 20 ns rising edge, is proposed in this paper. The proposed circuit has a separate detection component and an on-time control component which enable it to distinguish between electrostatic discharge (ESD) events and fast power-on events. As opposed to other on-time control techniques, instead of large resistors or capacitors, which can cause a large occupation of the layout area, we use a capacitive voltage-biased p-channel MOSFET in the on-time control part of the proposed circuit. The capacitive voltage-biased p-channel MOSFET is in the saturation region after the ESD event is detected, which can serve as a large equivalent resistance (~106 Ω) in the structure. The proposed power clamp circuit offers several advantages compared to the traditional circuit, such as having at least 70% area savings in the trigger circuit area (30% area savings in the whole circuit area), supporting a power supply ramp time as fast as 20 ns, dissipating the ESD energy more cleanly with little residual charge, and recovering faster from false triggers. The rail clamp circuit also offers robust performance in an industry-standard PVT (process, voltage, and temperature) space and has been verified by the simulation results. Showing good performance of human body model (HBM) endurance and high immunity to false trigger, the proposed power clamp circuit has great potential for application in ESD protection.

Epithelial-Mesenchymal Transition Expression Profile Stratifies Human Glioma into Two Distinct Tumor-Immune Subtypes.

Glioma is the primary tumor with the highest incidence and the worst prognosis in the human central nervous system. Epithelial-mesenchymal transition (EMT) and immune responses are two crucial processes that contribute to it having the worst prognosis. However, a comprehensive correlation between these two processes remains elusive. The mRNA expression profiles and corresponding clinical data of patients with glioma were downloaded from public databases. EMT-related genes were collected and provided in the dbEMT database. Risk scores, Lasso regression, and enrichment analysis were conducted for functional validation. In our study, we used unsupervised clustering of EMT gene expression profiles to classify gliomas into two subtypes. We assessed the reliability of this classification system by testing it in three independent cohorts. Each subtype had different clinical and immune system characteristics. The study suggests a possible link between EMT and immune responses in gliomas.

Correlation Analysis of Persistence and Recurrence of Stroke in Young Patients Based on Big Data in Healthcare.

This study aims to analyze the correlation between the persistence and recurrence of stroke in young patients via big data in healthcare. It provides an in-depth introduction to the background of big data in healthcare and a detailed description of stroke symptoms, so as to better apply the Apriori parallelization algorithm based on compression matrix (PBCM) algorithm against the background of big data in healthcare to analyze it. In our study, patients were randomly divided into 2 groups. By observing the different persistent relationships in the groups, the factors affecting the patients' fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), blood pressure (BP), blood lipids, alcohol consumption, smoking and so on were analyzed. The National Institute of Health Stroke Scale (NIHSS) score, FBG, HbA1c, triglycerides (TG), high-density lipoprotein (HDL), body mass index (BMI), length of hospital stay, gender and high BP, diabetes, heart disease, smoking and other factors affect the recurrence rate of stroke as they all affect the brain, although they are all statistically different (P < .05). The recurrence of stroke requires more attention in the treatment of stroke.

Efficacy and Safety of Bevacizumab for Treating Glioblastoma: A Systematic Review and Meta-Analysis of Phase II and III Randomized Controlled Trials.

OBJECTIVE: To fully investigate the efficacy and safety of bevacizumab for glioblastoma. METHODS: Databases were searched for phase II/III randomized controlled trials treated with bevacizumab. RESULTS: Bevacizumab significantly improved the PFS in glioblastoma patients, but did not prolong OS. PFS was significantly prolonged in both first-line and second-line treatment. Bevacizumab plus temozolomide was correlated with improved PFS for patients with different MGMT methylation status. Bevacizumab could increase the risk of hypertension, proteinuria, thromboembolic, and infection. Hypertension should be well concerned. CONCLUSIONS: Bevacizumab-containing regimen can significantly improve PFS, but did not prolong OS.

A Novel DTSCR Structure with High Holding Voltage and Enhanced Current Discharge Capability for 28 nm CMOS Technology ESD Protection.

To cope with the much narrower ESD design window in 28 nm CMOS technology, a novel diode-triggered silicon-controlled rectifier with an extra discharge path (EDP-DTSCR) for ESD protection is proposed in this paper. Compared with the traditional DTSCR, the proposed DTSCR has an enhanced current discharge capability that is achieved by creating a slave SCR path in parallel with the master SCR path. Moreover, the improved triggering and holding characteristic can be obtained by the proposed EDP-DTSCR. By sharing the anode emitter junction, a slave SCR path is constructed that is symmetrical to the position of the master SCR path to add an additional ESD discharge path to the EDP-DTSCR. In this way, the current discharge capability of the entire device is obviously improved. The TCAD simulation result shows that the proposed device has a remarkably lower on-resistance compared with the traditional DTSCR and the DTSCR with p-type guard ring (PGR-DTSCR). In addition, it is structurally optimized to further increase the holding voltage and reduce the trigger voltage to improve the anti-latching capability of the device, which is more conducive to the ESD protection window application of 28 nm CMOS technology.

Clinical Characteristics and Prognostic Risk Factors of Parasellar Chondrosarcoma.

Background: Parasellar chondrosarcomas are extremely rare. This study describes the characteristics of parasellar chondrosarcoma and analyzes the risk factors and prognosis based on the resection degree. Methods: Fifteen patients with pathologically diagnosed parasellar chondrosarcoma were retrospectively analyzed for the clinical data, surgical methods, and prognosis to identify relationships between the surgical resection degree, tumor recurrence, and imaging characteristics. Results: Twelve patients had eye dysfunction and ptosis. Differentiation from other parasellar tumors by imaging is difficult. The preoperative Karnofsky Performance Scale (KPS) score positively correlated with the tumor resection degree (p = 0.026) and negatively correlated with the maximum tumor diameter (p = 0.001). Tumor recurrence negatively correlated with the resection degree (p = 0.009). The postoperative KPS score positively correlated with the preoperative KPS score (p < 0.001) and tumor resection degree (p = 0.026), and negatively correlated with the maximum tumor diameter (p = 0.016) and age (p = 0.047). An improved KPS score positively correlated with the tumor resection degree (p = 0.039). Patients who underwent total resection of the chondrosarcoma had longer progression-free survival than those who underwent partial resection (p = 0.0322). Conclusion: Parasellar chondrosarcomas are difficult to resect completely. Preoperative KPS score is an important factor for the degree of resection. KPS score, age, maximum tumor diameter, and resection degree may be important prognostic factors.

Particle Size Inversion Constrained by L∞ Norm for Dynamic Light Scattering.

Particle size inversion of dynamic light scattering (DLS) is a typically ill-posed problem. Regularization is an effective method to solve the problem. The regularization involves imposing constraints on the fitted autocorrelation function data by adding a norm. The classical regularization inversion for DLS data is constrained by the L2 norm. In the optimization equation, the norm determines the smoothness and stability of the inversion result, affecting the inversion accuracy. In this paper, the Lp norm regularization model is constructed. When p is 1, 2, 10, 50, 100, 1000, and ∞, respectively, the influence of their norm models on the inversion results of data with different noise levels is studied. The results prove that overall, the inversion distribution errors show a downward trend with the increase of p. When p is larger than 10, there is no significant difference in distribution error. Compared with L2, L∞ can provide better performance for unimodal particles with strong noise, although this does not occur in weak noise cases. Meanwhile, L∞ has lower sensitivity to noise and better peak resolution, and its inverse particle size distribution is closer to the true distribution for bimodal particles. Thus, L∞ is more suitable for the inversion of DLS data.

Treatment of Fracture of the Calcaneus via Bone Axial X-Ray Image-Based Minimally Invasive Approach.

To discuss the values of two bone axial X-ray image-based minimally invasive approach surgeries in the diagnosis and treatment of fracture of the calcaneus, 80 patients diagnosed with fracture of the calcaneus by bone axial X-ray examination were selected and divided equally into the minimally invasive longitudinal approach (MILA) group (40 cases) and the sinus tarsal approach (STA) group (40 cases). Besides, the duration of operation, the incidence of complications, the time-to-start weight training, and the American Orthopaedic Foot and Ankle Society (AOFAS) foot function scoring system between the patients in the two groups were compared. The results showed that the duration of operation and incidence of complications among the patients in the MILA group (42.87 ± 5.12 minutes, 20%) were both superior to those among the patients in the STA group (60.43 ± 7.31 minutes, 32.5%). The time-to-start weight training in the MILA group was 5.2 weeks, which was obviously shorter than that in the STA group (5.7 weeks). The difference in AOFAS scores between the two groups was not significant. The walking pavement score in the MILA group (4.2 ± 0.37 points) was slightly higher than that in the STA group (3.3 ± 0.45 points), and the differences demonstrated statistical meaning (P < 0.05). To sum up, the bone axial X-ray image is an essential examination method of diagnosing fracture of the calcaneus. The two minimally invasive methods both showed good clinical therapeutic effects. The operation of MILA was relatively shorter with fewer complications and is worthy of being promoted as an effective treatment method of fracture of the calcaneus.

[Clinical and mechanism research on functional erectile dysfunction treated with moxibustion and qiangshen shugan qiwei decoction].

OBJECTIVE: To observe the clinical therapeutic effect on functional erectile dysfunction (FED) of kidney deficiency and liver stagnation treated by Baixiao moxibustion and qiangshen shugan qiwei decoction. METHODS: A total of 120 patients with FED were randomized into an observation group (60 cases, 2 cases dropped off) and a control group (60 cases, 4 cases dropped off). In the control group, the patients were treated with oral qiangshen shugan qiwei decoction (Radix Rehmanniae Praeparata, Rhizoma Dioscoreae, Rhizoma Curculiginis, Herba Epimedii, etc.), one dose daily. In the observation group, on the base of the treatment as the control group, Baixiao moxibustion was exerted along the distribution of governor vessel on the back, 30 min each time, once a week. The treatment duration was 4 weeks in the two groups. Before and after treatment, the scores of international index of erectile function-5 (IIEF5), erectile hardness scale (EHS), erectile dysfunction inventory of treatment satisfaction (EDITS) and TCM symptoms were observed in the patients of the two groups. Before and after treatment, the levels of serum sex hormones (testosterone [T], luteinizing hormone [LH], estradiol [E2], prolactin [PRL]) and the expressions of relevant proteins (matrix metalloproteinase-3 [MMP-3], matrix metalloproteinase-9 [MMP-9] and vascular endothelial growth factor [VEGF]) were determined in the patients of the two groups separately. The penile vascular function (peak systolic velocity [PSV], end-diastolic velocity [EDV], resistance index [RI]) was compared before and after treatment. Besides, the clinical therapeutic effect was evaluated. RESULTS: After treatment, the scores of IIEF5, EHS and EDITS were all increased as compared with the values before treatment (P<0.05), and the scores of TCM symptoms were reduced as compared with the values before treatment in the patients of the two groups (P<0.05). After treatment, the scores of IIEF5, EHS and EDITS in the observation group were higher than those in the control group (P<0.05), and the score of TCM symptoms was lower than the control group (P<0.05). After treatment, the levels of T and LH in serum of the two groups and the expressions of serum MMP-3 and MMP-9 in the observation group were all increased as compared with those before treatment (P<0.05), the levels of E2 and PRL in the observation group and VEGF expressions in the two groups were all reduced as compared with those before treatment (P<0.05). The levels of serum T and LH and the expressions of MMP-3 and MMP-9 in the observation groups were all higher than those in the control group (P<0.05), and the levels of E2 and PRL and VEGF expression were lower than the control group (P<0.05). After treatment, PSV was increased and EDV was reduced as compared with those before treatment in the patients of the two groups (P<0.05), RI in the observation group was reduced as compared with that before treatment (P<0.05). After treatment, PSV in the observation group was higher and EDV and RI were lower than the control group (P<0.05). The total effective rate was 87.9% (51/58) in the observation group, higher than 76.8% (43/56) in the control group (P<0.05). CONCLUSION: The combined therapy of Baixiao moxibustion and qiangshen shugan qiwei decoction effectively increases erectile function, erectile hardness and treatment satisfaction in the patients with functional erectile dysfunction of kidney deficiency and liver stagnation, as well as improves penile vascular function. The effect mechanism of this therapy may be related to the regulation of serum sex hormones and relevant proteins.

The Role of Vitamin D Intake on the Prognosis and Incidence of Lung Cancer: A Systematic Review and Meta-Analysis.

The correlation between vitamin D intake and lung cancer development is controversial. This meta-analysis aims to evaluate the relationship between vitamin D and the prognosis and incidence of lung cancer. A comprehensive database search on PubMed, Web of Science, EBSCO, and Cochrane Library was carried out from the beginning to November 2020. Long-term survival and the incidence rate of patients with lung cancer were the primary outcomes of the study. Ten eligible studies were selected for the meta-analysis following specific inclusion and exclusion criteria. Four included studies, covering 5,007 patients, compared the overall survival (OS) and relapse-free survival (RFS) of lung cancer patients among total vitamin D users with non-users. Significantly, the estimated pooled hazard ratio (HR) revealed that vitamin D could improve OS and RFS of lung cancer patients [HR=0.83, 95% CI (0.72-0.95); HR=0.79, 95% CI (0.61-0.97), respectively]. Vitamin D intake was inversely associated with lung cancer incidence in six studies [OR=0.90, 95% CI (0.83-0.97)]. The present meta-analysis shows vitamin D not only improves the long-term survival of lung cancer patients but has a beneficial effect on the incidence of lung cancer. Notwithstanding, more studies are needed to confirm the study results.

Effects of Folic Acid and Caffeic Acid on Indirect Photo-oxidation of Proteins and Their Costabilization under Irradiation.

Proteins, vitamins, and phenols are often present together in foods, but they are sensitive to environmental factors. Folic acid (FA), a synthetic form of folate, decomposes under light, leading to protein oxidation. Caffeic acid (CA), a phenolic acid, exhibits remarkable activity for scavenging reactive molecules. The exploitation of their interactions offers opportunities for designing the stabilizing system. In this study, FA-photodecomposition-induced protein (ß-lactoglobulin, α-lactalbumin, bovine serum albumin, and ß-casein) damage and its inhibition by CA were investigated in terms of protein composition and structural change. The results indicated that FA photoproducts oxidized the proteins via the electron transfer pathway, leading to degradation, aggregation, and unfolding. At the same time, photostability of FA, CA, and proteins in the tertiary mixture was better than that of any individual components. The antioxidant activity of the proteins contributed to their protection for FA. CA and its products inhibited FA photodecomposition and the photodecomposition-induced protein oxidation by trapping excited states.

Based on a Self-Feeder Layer, a Novel 3D Culture Model of Human ADSCs Facilitates Trans-Differentiation of the Spheroid Cells into Neural Progenitor-Like Cells Using siEID3 with a Laminin/Poly-d-lysine Matrix.

Human adipose-derived stromal cells (ADSCs) are receiving unprecedented attention as a potential cellular source for regenerative medicine-based therapies against various diseases and conditions. However, there still have significant issues concerning the translational development of ADSC-based therapies, such as its heterogeneity and being prone to aging. We developed a new simple and economical 3D semi-suspended expansion method in which 3D spheroids reside on an ADSC-derived self-feeder cell layer, producing cells with increased population homogeneity and strong stemness and ensuring that the proliferation and differentiation potency of the cells does not become notably reduced after at least ten passages in culture. To check the potential application of the 3D ADSC spheroids, we discovered that the combination of siEID3, which is a small interfering RNA of EP300 inhibitor of differentiation 3 (EID3), and laminin/poly-d-lysine matrix can rapidly result in trans-differentiation of the 3D spheroid cells to neural progenitor-like cells (NPLCs) in approximately 9 days in vitro. This approach provides a multidisciplinary tool for stem cell research and production in mesenchymal stem cell-related fields.

The Efficacy and Safety of Additional Anti-HER2-Targeting Drugs in the Treatment of HER2-Positive Advanced Breast Cancer: A Meta-Analysis.

BACKGROUND: HER2-positive breast cancer patients account for one-fifth of the total breast cancer population. Besides, more anti-HER2-targeting drugs have appeared clinically. OBJECTIVE: This study aimed to analyze the efficacy and safety of additional anti-HER2 (Human Epidermal growth Factor Receptor 2)-targeting drugs in the treatment of HER2-positive advanced breast cancers. METHODS: The following databases were searched for published articles containing data on the efficacy and safety of additional anti-HER2-targeting drugs in HER2-positive advanced breast cancer from the time of their inception until December 2019: PubMed, Web of Science, EBSCO, and Cochrane library. The primary outcomes were Progression-Free Survival (PFS) and Overall Survival (OS). RESULTS: The additional anti-HER2-targeting drugs significantly improved the PFS (HR: 0.66, p<0.001) and OS (HR: 0.77, p<0.001) of HER2-positive advanced breast cancer patients. Regarding drug types, lapatinib was the most effective (HR: 0.53, 95% Cl: 0.39-0.67, p<0.001), followed by pertuzumab (HR: 0.72, 95% Cl: 0.55-0.89, p=0.001). Trastuzumab was the least beneficial (HR: 0.87, 95% Cl: 0.31-1.44, p=0.594). Concerning treatment regimen, first-line treatment (HR: 0.67, 95% Cl: 0.52-0.82, p<0.001) was more effective than non-first-line treatment (HR: 0.82, 95% Cl: 0.71-0.94, p=0.004). The main Adverse Events (AEs) observed were diarrhea and decreased ejection fraction. CONCLUSION: Additional anti-HER2-targeting drugs can improve long-term prognosis in HER2-positive advanced breast cancers. Besides, they are associated with fewer AEs and are tolerable. Lapatinib is the most effective drug, followed by pertuzumab, whereas trastuzumab is the least effective. Concerning treatment, we recommend the use of anti-HER2-targeting drugs in first-line therapy of HER2-positive advanced breast cancers.

Correction to: LTBP1 plays a potential bridge between depressive disorder and glioblastoma.

An amendment to this paper has been published and can be accessed via the original article.

Depressive and anxiety disorders worsen the prognosis of glioblastoma.

Glioblastoma multiforme (GBM) is one of the most malignant tumors. Depressive and anxiety disorders may co-exist with GBM. We investigated whether depression and anxiety influenced the outcomes of GBM. The Patient Health Questionnaire 9-item (PHQ-9) and Generalized Anxiety Disorder 7-item (GAD-7) scales were used to investigate the mental condition of GBM patients in our department, and the overall survival times of these patients were monitored. The scores on both scales were higher in GBM patients than in healthy controls. For each scale, GBM patients were divided into high- and low-score groups based on the average score. The prognosis was poorer for GBM patients in the high-score groups than for those in the low-score groups. Moreover, magnetic resonance imaging revealed that tumor necrosis was more prevalent among high-scored GBM patients. Cellular experiments were performed on primary GBM cells from patients with either high or low scores on both scales. Sphere formation, EdU and wound healing assays revealed greater proliferation and invasion capacities in GBM cells from patients with high scores on both scales. Western blotting assay revealed significantly different expression of epithelial and mesenchymal markers between the two groups. Thus, our analysis revealed a clinically important correlation between depression/anxiety and GBM prognosis.

Aging-related tumor associated fibroblasts changes could worsen the prognosis of GBM patients.

Background: Glioblastoma multiforme (GBM) is the most malignant tumor in human brain, with highly heterogeneity among different patients. Age could function as an incidence and prognosis risk factor for many tumors. Method: A series of bioinformatic experiments were conducted to evaluate the differences of incidence, differential expressed genes, enriched pathways with the data from Surveillance, Epidemiology, and End Results (SEER) program, the cancer genome atlas (TCGA) and Chinese glioma genome atlas (CGGA) project. Results: We discovered in our present study that distinct difference of incidence and prognosis of different aged GBM patients. By a series of bioinformatic method, we found that the tumor associated fibroblasts (TAFs) was the most crucial tumor microenvironment (TME) component that led to this phenomenon. Epithelial-mesenchymal transition (EMT) could be the mechanism by which TAFs regulate the progression of GBM. Conclusion: We have proposed a close correlation between age and GBM incidence and prognosis, and propose the underlying mechanism behind this correlation by mining different databases, which laid the foundation for future research.