Advanced tumor electric fields therapy: A review of innovative research and development and prospect of application in glioblastoma.

BACKGROUND: Glioblastoma multiforme (GBM) is an aggressive malignant tumor with a high mortality rate and is the most prevalent primary intracranial tumor that remains incurable. The current standard treatment, which involves surgery along with concurrent radiotherapy and chemotherapy, only yields a survival time of 14-16 months. However, the introduction of tumor electric fields therapy (TEFT) has provided a glimmer of hope for patients with newly diagnosed and recurrent GBM, as it has been shown to extend the median survival time to 20 months. The combination of TEFT and other advanced therapies is a promising trend in the field of GBM, facilitated by advancements in medical technology. AIMS: In this review, we provide a concise overview of the mechanism and efficacy of TEFT. In addition, we mainly discussed the innovation of TEFT and our proposed blueprint for TEFT implementation. CONCLUSION: Tumor electric fields therapy is an effective and highly promising treatment modality for GBM. The full therapeutic potential of TEFT can be exploited by combined with other innovative technologies and treatments.

Prediction of bitterness based on modular designed graph neural network.

Motivation: Bitterness plays a pivotal role in our ability to identify and evade harmful substances in food. As one of the five tastes, it constitutes a critical component of our sensory experiences. However, the reliance on human tasting for discerning flavors presents cost challenges, rendering in silico prediction of bitterness a more practical alternative. Results: In this study, we introduce the use of Graph Neural Networks (GNNs) in bitterness prediction, superseding traditional machine learning techniques. We developed an advanced model, a Hybrid Graph Neural Network (HGNN), surpassing conventional GNNs according to tests on public datasets. Using HGNN and three other GNNs, we designed BitterGNNs, a bitterness predictor that achieved an AUC value of 0.87 in both external bitter/non-bitter and bitter/sweet evaluations, outperforming the acclaimed RDKFP-MLP predictor with AUC values of 0.86 and 0.85. We further created a bitterness prediction website and database, TastePD (https://www.tastepd.com/). The BitterGNNs predictor, built on GNNs, offers accurate bitterness predictions, enhancing the efficacy of bitterness prediction, aiding advanced food testing methodology development, and deepening our understanding of bitterness origins. Availability and implementation: TastePD can be available at https://www.tastepd.com, all codes are at https://github.com/heyigacu/BitterGNN.

MS/MS-based molecular networking discovery of sesquiterpenes from Carpesium abrotanoides L. with their cytotoxic and acetylcholinesterase inhibitory activity.

Employing an MS/MS-based molecular networking-guided strategy, three new eudesmane-type sesquiterpenes (1-3) and one undescribed pseudoguaianolide sesquiterpene (8), along with four known eudesmane-type sesquiterpene lactones (4-7) were extracted and purified from the herbs of Carpesium abrotanoides L. Structural elucidation encompassed comprehensive spectroscopic analysis, NMR calculations, DP4+ analysis, and ECD calculations. The cytotoxicity activity of all isolates was evaluated against two human hepatoma carcinoma cells (HepG2 and Hep3B) in vitro. It was demonstrated that compounds 2 and 4 showed moderate cytotoxic against HepG2 and Hep3B cells. Furthermore, all compounds were evaluated for their acetylcholinesterase (AChE) inhibitory activity. Particularly noteworthy is that, in comparison to the positive control, compound 1 demonstrated significant AChE inhibition with an inhibition rate of 77.86%. In addition, the inhibitory mechanism of compound 1 were investigated by in silico docking analyze and molecular dynamic simulation.

Mechanically Enhanced Detoxification of Chemical Warfare Agent Simulants by a Two-Dimensional Piezoresponsive Metal-Organic Framework.

Chemical warfare agents (CWAs) refer to toxic chemical substances used in warfare. Recently, CWAs have been a critical threat for public safety due to their high toxicity. Metal-organic frameworks have exhibited great potential in protecting against CWAs due to their high crystallinity, stable structure, large specific surface area, high porosity, and adjustable structure. However, the metal clusters of most reported MOFs might be highly consumed when applied in CWA hydrolysis. Herein, we fabricated a two-dimensional piezoresponsive UiO-66-F4 and subjected it to CWA simulant dimethyl-4-nitrophenyl phosphate (DMNP) detoxification under sonic conditions. The results show that sonication can effectively enhance the removal performance under optimal conditions; the reaction rate constant k was upgraded 45% by sonication. Moreover, the first-principle calculation revealed that the band gap could be further widened with the application of mechanical stress, which was beneficial for the generation of 1O2, thus further upgrading the detoxification performance toward DMNP. This work demonstrated that mechanical vibration could be introduced to CWA protection, but promising applications are rarely reported.

Myeloperoxidase Gene Deletion Causes Drastic Microbiome Shifts in Mice and Does Not Mitigate Dextran Sodium Sulphate-Induced Colitis.

Neutrophil-myeloperoxidase (MPO) is a heme-containing peroxidase which produces excess amounts of hypochlorous acid during inflammation. While pharmacological MPO inhibition mitigates all indices of experimental colitis, no studies have corroborated the role of MPO using knockout (KO) models. Therefore, we investigated MPO deficient mice in a murine model of colitis. Wild type (Wt) and MPO-deficient mice were treated with dextran sodium sulphate (DSS) in a chronic model of experimental colitis with three acute cycles of DSS-induced colitis over 63 days, emulating IBD relapse and remission cycles. Mice were immunologically profiled at the gut muscoa and the faecal microbiome was assessed via 16S rRNA amplicon sequencing. Contrary to previous pharmacological antagonist studies targeting MPO, MPO-deficient mice showed no protection from experimental colitis during cyclical DSS-challenge. We are the first to report drastic faecal microbiota shifts in MPO-deficient mice, showing a significantly different microbiome profile on Day 1 of treatment, with a similar shift and distinction on Day 29 (half-way point), via qualitative and quantitative descriptions of phylogenetic distances. Herein, we provide the first evidence of substantial microbiome shifts in MPO-deficiency, which may influence disease progression. Our findings have significant implications for the utility of MPO-KO mice in investigating disease models.

[Synthesis and tissue distribution of bufadienolides in Bufo bufo gargarizans].

This study explored the biosynthesis of bufadienolides(BDs) in Bufo bufo gargarizans to solve the dilemma of the decreasing resources of B. bufo gargarizans and provide a theoretical basis for the sustainable utilization of the resources. Ultra-high performance liquid chromatography-Orbitrap-mass spectrometry(UHPLC-Orbitrap-MS) was employed to detect the synthesis sites of BDs in B. bufo gargarizans, and the results were verified by desorption electrospray ionization-mass spectrometry imaging(DESI-MSI) and homogenate incubation experiments. BDs in B. bufo gargarizans had the highest content in the liver and the highest concentration in the gallbladder, in addition to the parotid gland and skin, which suggested that the liver could synthesize BDs. The results of DESI-MSI also showed that BDs were mainly enriched in the liver rather than the immature parotid gland. The incubation experiment of liver homogenates demonstrated the liver of B. bufo gargarizans had the ability to synthesize BDs. This study showed that the liver was a major organ for the synthesis of BDs in B. bufo gargarizans during metamorphosis, development, and growth, which provided strong theoretical support for the biosynthesis of BDs and the sustainable utilization of B. bufo gargarizans resources.

How dyadic appraisal moderate the association between dyadic coping and diabetes management efficacy.

To explore the moderating role of dyadic appraisal in the association between dyadic coping and diabetes management efficacy. Two hundred seventy six middle-aged and older couple pairs with one spouse who had diabetes were recruited from 14 community healthcare centers across Guangzhou. The moderating role of dyadic appraisal was investigated using the actor-partner interdependence moderation model. When both couples considered diabetes to be a shared condition, statistically-significant associations were found between patients' negative (ß = -22.7, p = 0.008) and neutral behaviors (ß = 13.6, p = 0.017), plus spouses' positive behaviors (ß = 22.8, p = 0.009) on their own diabetes management efficacy, respectively (i.e. actor effects); as well as between spouses' positive (ß = 16.8, p = 0.028), negative (ß = -28.5, p < 0.001), and neutral behaviors (ß = 16.9, p = 0.006) on patient's diabetes management efficacy (i.e. partner effects). Dyadic appraisal moderates the association between dyadic coping and diabetes management efficacy.

Exosome-transmitted podoplanin promotes tumor-associated macrophage-mediated immune tolerance in glioblastoma.

AIMS: Glioblastoma is the most frequent and aggressive primary brain tumor, characterized by rapid disease course and poor treatment responsiveness. The abundance of immunosuppressive macrophages in glioblastoma challenges the efficacy of novel immunotherapy. METHODS: Bulk RNA-seq and single-cell RNA-seq of glioma patients from public databases were comprehensively analyzed to illustrate macrophage infiltration patterns and molecular characteristics of podoplanin (PDPN). Multiplexed fluorescence immunohistochemistry staining of PDPN, GFAP, CD68, and CD163 were performed in glioma tissue microarray. The impact of PDPN on macrophage immunosuppressive polarization was investigated using a co-culture system. Bone marrow-derived macrophages (BMDMs) and OT-II T cells isolated from BALB/c and OT-II mice respectively were co-cultured to determine T-cell adherence. Pathway alterations were probed through RNA sequencing and western blot analyses. RESULTS: Our findings demonstrated that PDPN is notably correlated with the expression of CD68 and CD163 in glioma tissues. Additionally, macrophages phagocytosing PDPN-containing EVs (EVsPDPN ) from GBM cells presented increased CD163 expression and augmented secretion of immunoregulatory cytokine (IL-6, IL-10, TNF-α, and TGF-ß1). PDPN within EVs was also associated with enhanced phagocytic activity and reduced MHC II expression in macrophages, compromising CD4+ T-cell activation. CONCLUSIONS: This investigation underscores that EVsPDPN derived from glioblastoma cells contributes to M2 macrophage-mediated immunosuppression and is a potential prognostic marker and therapeutic target in glioblastoma.

Effect of two different modalities of hysterectomy on wound infection and wound dehiscence in obese patients.

This research intended to investigate the influence of the operation of both kinds of hysterectomies in the risk of wound infection and the degree of wound dehiscence. Both of them were open field and laparoscope. In this research, we looked into four databases: PubMed, Web of Science, Embase and Cochrane Library. Research was conducted on various operative methods for hysterectomy in obese patients between 2000 and October 2023. Two independent investigators performed an independent review of the data, established the inclusion and exclusion criteria, and managed the results with Endnote software. It also evaluated the quality of the included literature. Finally, the data were analysed with RevMan 5.3. This study involved 874 cases, 387 cases received laparoscopy and 487 cases received open access operation. Our findings indicate that there is a significant reduction in the rate of post-operative wound infection among those who have received laparoscopy compared with who have received open surgical procedures (odds ratio [OR], 0.04; 95% confidence interval [CI], 0.01-0.15; p < 0.001); There was no statistical difference between the rate of post-operative wound dehiscence and those who received laparotomy compared with those who received open surgical procedures (OR, 0.33; 95% CI, 0.10-1.11; p = 0.07); The estimated amount of blood lost during the operation was less in the laparoscopy group compared with the open procedure (mean difference, -123.72; 95% CI, -215.16 to -32.28; p = 0.008). Generally speaking, the application of laparoscopy to overweight women who have had a hysterectomy results in a reduction in the expected amount of bleeding during surgery and a reduction in the risk of post-operative wound infections.

Tonghua Liyan granules in the treatment of Laryngopharyngeal reflux disease with stagnation of phlegm and qi syndrome: a randomized, double-blind, placebo-controlled study.

Background: Laryngopharyngeal reflux disease (LPRD) is an extraesophageal syndromic manifestation of gastroesophageal reflux disease (GERD). Despite the increasing incidence of and concern about LPRD, treatment with proton pump inhibitors (PPIs) is unsatisfactory. Here, LPRD was treated with Tonghua Liyan (THLY) granules in combination with PPIs to evaluate treatment efficacy and possible adverse reactions. Methods: Seventy-six LPRD patients with stagnation of phlegm and qi syndrome (SPQS) were randomly divided into an experimental group and a control group. The experimental group received THLY granules combined with rabeprazole capsules. The control group received THLY granule placebo combined with rabeprazole capsules. A parallel, randomized, double-blind, placebo-controlled clinical trial was conducted with these two groups. The treatment cycle was 8 weeks. The reflux symptom index (RSI), clinical symptom score, salivary pepsin content, reflux finding score (RFS) and gastroesophageal reflux disease questionnaire (GerdQ) were used to evaluate clinical efficacy. The final efficacy rate was evaluated according to the RSI and clinical symptom score. Results: Compared with those at baseline, all the indicators in the experimental group and control group significantly improved (p < 0.01). In terms of the RSI, clinical symptom score, and RFS, the experimental group had a higher degree of improvement (p < 0.05), and the overall efficacy rate was higher (p < 0.05). In terms of the salivary pepsin concentration and GerdQ, there was no significant difference between the test group and the control group (p > 0.05). Both groups of safety indicators showed no abnormalities and did not cause any allergic reactions in the body. Conclusion: Compared with PPIs alone, THLY granules combined with PPIs are more effective in the treatment of LPRD patients with SPQS in terms of symptoms and signs. This combination treatment, because of its higher clinical efficacy and lack of obvious adverse reactions, is worthy of clinical promotion and further in-depth study. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR2100046614.

Microglia in Microbiota-Gut-Brain Axis: A Hub in Epilepsy.

There is growing concern about the role of the microbiota-gut-brain axis in neurological illnesses, and it makes sense to consider microglia as a critical component of this axis in the context of epilepsy. Microglia, which reside in the central nervous system, are dynamic guardians that monitor brain homeostasis. Microglia receive information from the gut microbiota and function as hubs that may be involved in triggering epileptic seizures. Vagus nerve bridges the communication in the axis. Essential axis signaling molecules, such as gamma-aminobutyric acid, 5-hydroxytryptamin, and short-chain fatty acids, are currently under investigation for their participation in drug-resistant epilepsy (DRE). In this review, we explain how vagus nerve connects the gut microbiota to microglia in the brain and discuss the emerging concepts derived from this interaction. Understanding microbiota-gut-brain axis in epilepsy brings hope for DRE therapies. Future treatments can focus on the modulatory effect of the axis and target microglia in solving DRE.

DNA and RNA Stability of Marine Microalgae in Cold-Stored Sediments and Its Implications in Metabarcoding Analyses.

The ever-increasing applications of metabarcoding analyses for environmental samples demand a well-designed assessment of the stability of DNA and RNA contained in cells that are deposited or buried in marine sediments. We thus conducted a qPCR quantification of the DNA and RNA in the vegetative cells of three microalgae entrapped in facsimile marine sediments and found that >90% of DNA and up to 99% of RNA for all microalgal species were degraded within 60 days at 4 °C. A further examination of the potential interference of the relic DNA of the vegetative cells with resting cyst detection in sediments was performed via a metabarcoding analysis in artificial marine sediments spiked with the vegetative cells of two Kareniaceae dinoflagellates and the resting cysts of another three dinoflagellates. The results demonstrated a dramatic decrease in the relative abundances of the two Kareniaceae dinoflagellates in 120 days, while those of the three resting cysts increased dramatically. Together, our results suggest that a positive detection of microalgae via metabarcoding analysis in DNA or RNA extracted from marine sediments strongly indicates the presence of intact or viable cysts or spores due to the rapid decay of relic DNA/RNA. This study provides a solid basis for the data interpretation of metabarcoding surveys, particularly in resting cyst detection.

Integrated transcriptomic analysis systematically reveals the heterogeneity and molecular characterization of cancer-associated fibroblasts in osteosarcoma.

BACKGROUND: Osteosarcoma (OS), with a peak incidence during the adolescent growth spurt, is correlated with poor prognosis for its high malignancy. The tumor microenvironment (TME) is highly complicated, with frequent interactions between tumor and stromal cells. The cancer-associated fibroblasts (CAFs) in the TME have been considered to actively involve in the progression, metastasis, and drug resistance of OS. This study aimed to characterize cellular heterogeneity and molecular characterization in CAFs subtypes and explore the potential targeting therapeutic strategies to improve the prognosis of OS patients. METHODS: The single-cell atlas of human OS tumor lesions were constructed from the GEO database. Then significant marker genes and potential biological functions for each CAFs subtype were identified and explored using the Seurat R package. Next, by performing the survival analyses and constructing the risk scores for CAFs subtypes, we aimed to identify and characterize the prognostic values of specific marker genes and different CAFs subtypes. Furthermore, we explored the therapeutic targets and innovative drugs targeting different CAFs subtypes based on the GDSC database. Finally, prognoses related CAFs subtypes were further validated through immunohistochemistry (IHC) on clinical OS specimens. RESULTS: Overall, nine main cell clusters and five subtypes of CAFs were identified. The differentially expressed marker genes for each CAFs clusters were then identified. Moreover, through Gene Ontology (GO) enrichment analysis, we defined the CAFs_2 (upregulated CXCL14 and C3), which was closely related to leukocyte migration and chemotaxis, as inflammatory CAFs (iCAFs). Likewise, we defined the CAFs_4 (upregulated CD74, HLA-DRA and HLA-DRB1), which was closely related to antigen process and presentation, as antigen-presenting CAFs (apCAFs). Furthermore, Kaplan-Meier analyses showed that CAFs_2 and CAFs_4 were correlated with poor clinical prognosis of OS patients. Meanwhile, therapeutic drugs targeting CAFs_2 and CAFs_4, such as 17-AAG/Docetaxel/Bleomycin and PHA-793887/NG-25/KIN001-102, were also explored, respectively. Finally, IHC assay confirmed the abundant CAFs_2 and CAFs_4 subtypes infiltration in the OS microenvironment compared with adjacent tissues. CONCLUSION: Our study revealed the diversity, complexity, and heterogeneity of CAFs in OS, and complemented the single-cell atlas in OS TME.

Size-controllable synthesis of large-size spherical 3D covalent organic frameworks as efficient on-line solid-phase extraction sorbents coupled to HPLC.

BACKGROUND: Covalent organic frameworks (COFs) have found promising applications in separation fields due to their large surface area and high adsorption capacity, but the exiting COFs can not be directly used as the packing materials of on-line solid-phase extraction (SPE) coupled to HPLC and HPLC because their nano/submicron size or irregular shapes might cause ultrahigh column back pressure and low column efficiency. To synthesize the large-size spherical COFs larger than 3 µm as sorbents might be able to address these problems, however it is still a great challenge till now. RESULTS: In this work, two large-size spherical 3D COFs (COF-320 and COF-300) were size-controllably synthesized within 10-90 µm via a two-step strategy. These two spherical COFs showed large surface area, fine crystallinity, good chemical/mechanical stability, and good reproducibility. As an application case, when used as the on-line SPE sorbents coupled to HPLC, the large-size spherical COF-320 displayed high binding capacity for bisphenol F (Qmax of 452.49 mg/g), low column back pressure (6-8 psi at flow rate of 1 mL/min), and good reusability (at least 30 cycles). The developed on-line-SPE-HPLC-UV method presented good analytical performance with enrichment factor of 667 folds, linear range of 1.0-400 ng/mL, limit of detection (LOD, S/N = 3) of 0.3 ng/mL, limit of quantification (LOQ, S/N = 10) of 1.0 ng/mL, and recoveries of 100.3-103.2 % (RSDs of 2.0-3.5 %) and 95.2-97.0 % (RSDs of 4.3-5.6 %) for tap water and lake water samples, respectively. SIGNIFICANCE: This is the first case to synthesize the large-size spherical COFs within 10-90 µm, and this work made it possible to directly use COFs as the filling materials of on-line SPE coupled to HPLC and HPLC. The developed analytical method can be potentially applied to the rapid and sensitive detection of trace bisphenol F in environmental water samples.

Study on the Mechanism of Interaction between Dipeptidyl Peptidase 4 and Inhibitory Peptides Based on Gaussian Accelerated Molecular Dynamic Simulation.

Dipeptidyl peptidase 4 (DPP4) inhibitors can effectively inhibit the activity of DPP4, increasing the concentrations of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which allows for them to effectively contribute to the reduction of blood sugar levels. Leu-Pro-Ala-Val-Thr-Ile-Arg (LPAVTIR) and Leu-Pro-Pro-Glu-His-Asp-Trp-Arg (LPPEHDWR) were the two peptides with the strongest inhibitory activity against DPP4 selected from silkworm pupa proteins. In this study, four systems were established: Apo (ligand-free DPP4), IPI (IPI-bound DPP4), LPAVTIR (LPAVTIR-bound DPP4), LPPEHDWR (LPPEHDWR-bound DPP4), and Gaussian accelerated molecular dynamic (GaMD) simulation was conducted to investigate the mechanism of action of two inhibitory peptides binding to DPP4. Our study revealed that the LPAVTIR peptide possessed a more stable structure and exhibited a tighter binding to the Ser630 active site in DPP4, thus exhibiting a favorable competitive inhibition effect. In contrast, the LPPEHDWR peptide caused the horizontal α-helix (residues 201-215) composed of Glu205 and Glu206 residues in DPP4 to disappear. The spatial arrangement of active sites Ser630 relative to Glu205 and Glu206 was disrupted, resulting in enzyme inactivation. Moreover, the size of the substrate channel and cavity volume was significantly reduced after the binding of the inhibitory peptide to the protein, which was an important factor in the inhibition of the enzyme activity. A similar effect was also found from IPI (our positive control). By stabilizing the active site of DPP4, the IPI peptide induced the disappearance of the horizontal α-helix and a notable reduction in the active cavity volume. In conclusion, our study provided a solid theoretical foundation for the inhibitory mechanisms of IPI, LPAVTIR, and LPPEHDWR on DPP4, offering valuable insights for advancing the development of drug targets for type 2 diabetes.

Association between circulating biomarkers and non-alcoholic fatty liver disease: An integrative Mendelian randomization study of European ancestry.

BACKGROUND AND AIM: Circulating biomarkers provide potential diagnostic or prognostic information on disease presentation, progression or both. Early detection of circulating risk biomarkers is critical for non-alcoholic fatty liver disease (NAFLD) prevention. We aimed to systematically assess the potential causal relationship of genetically predicted 60 circulatory biomarkers with NAFLD using a two-sample Mendelian randomization (MR) design. METHODS AND RESULTS: We extracted instrumental variables for 60 circulating biomarkers, and obtained genome-wide association data for NAFLD from 3 sources [(including Anstee, FinnGen and UK Biobank (N ranges: 19264-377988)] among individuals of European ancestry. Our primary method was inverse-variance weighted (IVW) MR, with a series of additional and sensitivity analyses to test the hypothesis of MR. MR results showed that genetically predicted higher density lipoprotein-cholesterol (odds ratio (OR) = 0.86, 95% confidence interval (CI): 0.77-0.96) and vitamin D (OR = 0.39, 95% CI: 0.19-0.78) levels decreased the risk of NAFLD, whereas genetically predicted higher alanine (OR = 1.68, 95% CI: 1.21-2.33), histidine (OR = 1.21, 95% CI: 1.00-1.46), lactate (OR = 2.64, 95% CI: 1.09-6.39), triglycerides (OR = 1.16, 95% CI: 1.05-1.13), ferritin (OR = 1.17, 95% CI: 1.01-1.37), serum iron (OR = 1.23, 95% CI: 1.07-1.41) and transferrin saturation (OR = 1.16, 95% CI: 1.05-1.29), component 4 (OR = 1.10, 95% CI: 1.01-1.20), interleukin-1 receptor antagonist (OR = 1.12, 95% CI: 1.04-1.21) and interleukin-6 (OR = 1.62, 95% CI: 1.14-2.30) levels increased the risk of NAFLD. CONCLUSIONS: The findings might aid in elucidating the underlying processes of these causal relationships and provide strong evidence for focusing on high-risk populations and the therapeutic management of specific biomarkers.

Prognosis of Elevated Mitral Valve Pressure Gradient After Transcatheter Edge-to-Edge Repair: Systematic Review and Meta-Analysis.

Elevation in mitral valve pressure gradient (MVPG) after mitral valve transcatheter edge-to-edge repair (M-TEER) is common, however, evidence on its prognosis is scarce and debatable. Thus, this study aims to investigate the impact of increased MVPG after M-TEER on outcomes. Studies reporting the associations between the elevated MVPG after M-TEER and outcomes were identified in a systematic search of published literatures. Associations were pooled by meta-analysis using a random-effects model. The primary outcome was the composite of all-cause mortality and heart failure (HF) hospitalization. Seven observational studies with 2,730 patients (mean age, 77.7 ± 9.3 years; male, 64.4%; functional mitral regurgitation [MR], 65.2%) were eligible for the present analysis. M-TEER was performed entirely using the MitraClip system (Abbott), followed by 29.7% of patients having increased MVPG. Elevated postprocedural MVPG was not associated with a higher risk of the primary outcome, compared to low MVPG [hazard ratio (HR) = 1.22; 95% confidence interval (CI) 0.95-1.58; p = 0.12; I2 = 53.5%). However, the prognosis of elevated MVPG was observed in degenerative MR patients (HR = 1.37; 95% CI 1.03-1.84; p = 0.03; I2 = 0%), whereas not in functional MR patients. Patients with low MVPG + high residual MR had a higher risk of the primary outcome than those with high MVPG + low residual MR after M-TEER (HR = 1.50; 95% CI 1.10-2.03; p = 0.01; I2 = 13%). In conclusion, elevated MVPG seems to predict adverse outcomes mainly in patients with degenerative MR. Future studies are needed to prove these findings.

Prognostic factors and novel nomograms for overall survival and cancer specific survival of malignant ovarian cancer patients with bone metastasis: A SEER-based study.

OBJECTIVE: Ovarian cancer (OC) is a frequent and fatal disease in women, and bone metastasis of ovarian cancer (OCBM) leads to a poor survival trend. This study aimed to determine the factors which influence overall survival (OS) and cancer-specific survival (CSS) of OCBM patients and to develop prognostic predictive models. METHODS: Data of OCBM patients were stratified from the Surveillance, Epidemiology and End Results database from 2010 to 2017 and were randomly divided into training and testing datasets (7:3). Prognostic factors were identified by Cox regression analyses and nomograms were then developed. Nomogram models were examined on the discriminative ability and accuracy by calibration plots, Brier score (BS), and time-dependent receiver operating characteristic (ROC) curves. Decision curve analyses (DCA) was used for estimation of the clinical benefit of nomogram models. RESULTS: Grade, tumor size, tumor metastasis (liver, lung), primary site surgery, chemotherapy, and systemic therapy were realized as independent prognostic factors for OS and CSS, respectively. Agreement between the actual and predicted outcomes was proved by calibration plots. Nomograms performed well in OS and CSS predictions, as shown by area under the ROC curves (AUCs) and BSs for testing dataset as follows: for OS, 3-/6-/12-month AUCs and BSs were 0.778/0.788/0.822 and 19.0/18.5/15.4, respectively; for CSS, 3-/6-/12-month AUCs and BSs were 0.799/0.806/0.832 and 18.1/18.0/15.4, respectively. DCA suggested an agreeable clinical benefit of both nomograms. CONCLUSION: The nomograms developed for OCBM patients' survival prediction were proved to be accurate, efficient, and clinically beneficial, which were further deployed as web-based calculators to help in clinical decision making and future studies.

The value of radiographic features in predicting postoperative facial nerve function in vestibular schwannoma patients: A retrospective study and nomogram analysis.

OBJECTIVE: The purpose of this study was to identify significant prognostic factors associated with facial paralysis after vestibular schwannoma (VS) surgery and develop a novel nomogram for predicting facial nerve (FN) outcomes. METHODS: Retrospective data were retrieved from 355 patients who underwent microsurgery via the retrosigmoid approach for VS between December 2017 and December 2022. Univariate and multivariate logistic regression analysis were used to construct a radiographic features-based nomogram to predict the risk of facial paralysis after surgery. RESULTS: Following a thorough screening process, a total of 185 participants were included. The univariate and multivariate logistic regression analysis revealed that tumor size (p = 0.005), fundal fluid cap (FFC) sign (p = 0.014), cerebrospinal fluid cleft (CSFC) sign (p < 0.001), and expansion of affected side of internal auditory canal (IAC) (p = 0.033) were independent factors. A nomogram model was constructed based on these indicators. When applied to the validation cohort, the nomogram demonstrated good discrimination and favorable calibration. Then we generated a web-based calculator to facilitate clinical application. CONCLUSION: Tumor size, FFC and CSFC sign, and the expansion of the IAC, serve as good predictors of postoperative FN outcomes. Based on these factors, the nomogram model demonstrates good predictive performance.

A Human Adenovirus C Infection-Related Gene Panel for Predicting Survival and Treatment Responsiveness in Glioma Patients.

BACKGROUND: Viruses are critical for the regulation of cancer development and for therapy. Human adenovirus C (HadVC) has been detected in central nervous system and glioma tissue. The objective of the present study was the development of a robust prognostic model based on HadVC infection (HadVCi)-relevant genes. METHODS: The genome, transcriptome, and virome were systemically analyzed using The Cancer Genome Atlas dataset for training and 2 cohorts from the Chinese Glioma Genome Atlas and an immunotherapy trial cohort with 17 patients receiving anti-PD-1 treatment for validation. HadVCi-relevant gene selection from differentially expressed genes between HadVC-infected and non-HadVC-infected glioma patients using least absolute shrinkage and selection operator regression was followed by Cox regression modeling to establish a prognostic HadVCi score. Kaplan-Meier and receiver operating characteristic curve analyses were performed to estimate the predictive capacity of the HadVCi score. The χ2, Spearman, and Mann-Whitney U tests were used to identify the correlation with the clinicopathological parameters, treatment responsiveness, and immune landscape. Temozolomide-resistant glioma cells were established and analyzed at the transcriptional level using RNA sequencing data. RESULTS: The HadVCi score was (-0.2526673∗TRPC6) + (-0.2244276∗RNF207) + (-0.0894468∗SEC31B) + (-0.0190214∗ZCRB1) + (-0.017122∗DNPH1) + (0.0495818∗CCDC34) + (0.1196349∗PURG) + (0.1778997∗LILRA5). The score possesses a strong ability to predict overall survival. Further analysis revealed a higher HadVCi score correlated with a malignant phenotype and poorer treatment responsiveness to temozolomide-based chemotherapy and combined therapies. Additionally, transcriptomic analysis showed malignancy-, stemness-, and radioresistant-related gene activation in the HadVCi group, which characterized the poor outcomes and limited sensitivity to standard therapy. CONCLUSIONS: The HadVCi score could be an effective tool for survival prediction and treatment guidance for patients with glioma.