Background
Tumor‐treating field (TTFields) was a novel antitumor therapy that provided significant survival for previously treated metastatic non‐small cell lung cancer (mNSCLC). The consistency of ...the cost of the new treatment regimen with its efficacy was the main objective of the study.
Methods
The primary parameters, derived from the Phase 3 LUNAR study, were collected to evaluate the cost and efficacy of TTFields plus standard‐of‐care (SOC) (immune checkpoint inhibitors ICIs and docetaxel DTX) or SOC in patients with mNSCLC by establishing a three‐state Markov model over a 15‐year time horizon. Primary outcome measures for this study included costs, life‐years (LYs), quality‐adjusted LYs (QALYs), and incremental cost‐effectiveness ratios (ICERs). Sensitivity analyses were performed.
Results
The total costs of TTFields plus SOC, TTFields plus ICI, and TTFields plus DTX were $319,358, $338,688, and $298,477, generating 1.23 QALYs, 1.58 QALYs, and 0.89 QALYs, respectively. The ICERs of TTFields plus SOC versus SOC, TTFields plus ICI versus ICI, and TTFields plus DTX versus DTX were $613,379/QALY, $387,542/QALY, and $1,359,559/QALY, respectively. At willingness‐to‐pay (WTP) thresholds of $150,000/QALY, the probability of combination TTFields being cost‐effective was 0%. In addition, TTFields plus SOC exhibited similar efficacy (1.12 QALYs and 1.14 QALYs) and costs ($309,822 and $312,531) in the treatment of squamous cell carcinoma (SCC) and non‐squamous cell carcinoma (NSCC) populations.
Conclusions
In the United States, TTFields plus SOC as second‐line treatment was not a more cost‐effective strategy for patients with mNSCLC. Of the analyzed regimens, TTFields plus ICI was associated with most significant health benefits.
We evaluated the cost‐effectiveness of TTFields plus SOC versus SOC. TTFields plus ICI has the most advantageous health benefits in mNSCLC. TTFields plus SOC is not a more cost‐effectivenss strategy for mNSCLC in the USA.
Many randomized controlled trials have indicated that immuno-chemotherapy could generate clinical benefits, though the cost of immuno-chemotherapy was so prohibitive and the options were varied. This ...investigation aimed at evaluating effectiveness, safety, and cost-effectiveness for immuno-chemotherapy as a first-line therapeutic option for ES-SCLC patients.
Multiple scientific literature repositories were searched for clinical studies where immuno-chemotherapy was regarded as the first-line treatment for ES-SCLC, which were published in English between Jan 1, 2000, and Nov 30, 2021. This study conducted a network meta-analysis (NMA) and cost-effectiveness analysis (CEA) based upon US-resident payer perspectives. Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were evaluated through NMA. In addition, costings, life-years (LYs), quality-adjusted life-years (QALYs), and incremental cost-benefit ratio (ICER) were estimated by CEA.
We identified 200 relevant search records, of which four randomized controlled trials (RCTs) (2,793 patients) were included. NMA demonstrated that the effect of atezolizumab plus chemotherapy was ranked at a more elevated position in comparison to other immuno-chemotherapy options and chemotherapy alone, within the general population. The influence of atezolizumab plus chemotherapy and durvalumab plus chemotherapy was ranked higher within populations experiencing non-brain metastases (NBMs) andbrain metastases (BMs), respectively. The CEA revealed that the ICERs of immuno-chemotherapy over chemotherapyalone were higher than the willingness-to-pay (WTP) threshold of $150,000/QALY in any population. However, treatment with atezolizumab plus chemotherapy and durvalumab plus chemotherapy were more favorable health advantages than other immuno-chemotherapy regimens and chemotherapy alone, and the results were 1.02 QALYs and 0.89 QALYs within overall populations and populations with BMs, respectively.
The NMA and cost-effectiveness investigation demonstrated that atezolizumab plus chemotherapy could be an optimal first-line therapeutic option for ES-SCLC when compared with other immuno-chemotherapy regimens. Durvalumab plus chemotherapy is likely to be the most favorable first-line therapeutic option for ES-SCLC with BMs.
PAX1 gene methylation plays an important role in the development of cervical cancer. However, its prognostic value after radiotherapy for locally advanced cervical cancer is unknown, so this study ...aimed to investigate the value of PAX1 gene methylation for predicting the sensitivity of radiotherapy for cervical cancer.
We selected 125 patients with primary cervical cancer who underwent concurrent chemo-radiotherapy as the study population, quantitative methylation-specific polymerase chain reaction (QMSP) was used for detecting PAX1 methylation status of cervical exfoliated cells. Logistic regression model was used to analyze the risk factors associated with the short-term efficacy and to establish a prediction model of radiotherapy sensitivity based on PAX1 gene methylation. Cell viability after radiation of Hela and SiHa cells transfected with PAX1 or control vector was evaluated by CCK8. Furthermore, RNA-Seq analyses identified different expressed genes (DEGs) in PAX1 overexpressed SiHa cells. Gene Ontology (GO) and pathway enrichment analysis was carried out to determine the biological function of DEGs.
PAX1 methylation level was associated with HPV16/18-positive rate. PAX1 hypomethylation was found to be a risk factor for tumor residual after chemo-radiotherapy. A nomogram containing the risk factors for PAX1 methylation status, lymph node metastasis, pathological type and tumor size was further constructed to predict the probability of tumor residual after chemo-radiotherapy (AUC = 0.823, 95% CI 0.736-0.910). High PAX1 protein level was more likely to cause radioresistance in both Hela and SiHa cells. Transcriptomic sequencing of PAX1 overexpressed and control cells identified 615 differentially expressed genes, and GO enrichment analysis suggested that PAX1 may be involved in the regulation of signaling receptor activity and response to viruses.
PAX1 hypomethylation status could be used as a promising biomarker to predict radioresistance in cervical cancer. This further provides a new idea for the individualized treatment strategy of simultaneous radiotherapy for cervical cancer.
Transcription factors (TFs) are the mainstay of cancer and have a widely reported influence on the initiation, progression, invasion, metastasis, and therapy resistance of cancer. However, the ...prognostic values of TFs in breast cancer (BC) remained unknown. In this study, comprehensive bioinformatics analysis was conducted with data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. We constructed the co-expression network of all TFs and linked it to clinicopathological data. Differentially expressed TFs were obtained from BC RNA-seq data in TCGA database. The prognostic TFs used to construct the risk model for progression free interval (PFI) were identified by Cox regression analyses, and the PFI was analyzed by the Kaplan-Meier method. A receiver operating characteristic (ROC) curve and clinical variables stratification analysis were used to detect the accuracy of the prognostic model. Additionally, we performed functional enrichment analysis by analyzing the differential expressed gene between high-risk and low-risk group. A total of nine co-expression modules were identified. The prognostic index based on 4 TFs (NR3C2, ZNF652, EGR3, and ARNT2) indicated that the PFI was significantly shorter in the high-risk group than their low-risk counterpart (p < 0.001). The ROC curve for PFI exhibited acceptable predictive accuracy, with an area under the curve value of 0.705 and 0.730. In the stratification analyses, the risk score index is an independent prognostic variable for PFI. Functional enrichment analyses showed that high-risk group was positively correlated with mTORC1 signaling pathway. In conclusion, the TF-related signature for PFI constructed in this study can independently predict the prognosis of BC patients and provide a deeper understanding of the potential biological mechanism of TFs in BC.
Helicase‑like transcription factor (HLTF) has been identified as a tumor suppressor gene. The hypermethylation of HTLF is frequently observed in various types of cancer, including colorectal ...cancer (CRC). However, the mechanisms through which HLTF suppresses CRC progression remain unclear. Thus, the aim of the present study was to explore the biological function of HLTF in CRC cells and the underlying mechanisms. CRC tissues and cells were used to detect the expression of HLTF. Wound‑healing and Transwell assays were performed to assess the motility of CRC cells. The results revealed that HLTF expression was significantly associated with the differentiation status, invasion depth, lymph node metastasis and distant metastasis. A low HLTF expression was significantly associated with a poor survival. Furthermore, HTLF knockdown or ectopic overexpression significantly promoted or suppressed the motility of CRC cells, respectively. With regard to the underlying molecular mechanisms, the protein expression of HTLF was upregulated when the CRC cells were stimulated with transforming growth factor (TGF)‑β, and HLTF upregulation induced an increase in SMAD4 and p‑SMAD2/3 expression and a decrease in levels of the TGF‑β/SMAD pathway downstream genes, Vimentin and zinc finger e‑box binding homeobox 1 (ZEB1). On the whole, the findings of this study suggest that HLTF is negatively associated with the progression of CRC, and its overexpression suppresses the migration and invasion of CRC cells by targeting the TGF‑β/SMAD pathway.
Abstract Exploration of metastable phases holds profound implications for functional materials. Herein, we engineer the metastable phase to enhance the thermoelectric performance of germanium ...selenide (GeSe) through tailoring the chemical bonding mechanism. Initially, AgInTe 2 alloying fosters a transition from stable orthorhombic to metastable rhombohedral phase in GeSe by substantially promoting p ‐state electron bonding to form metavalent bonding (MVB). Besides, extra Pb is employed to prevent a transition into a stable hexagonal phase at elevated temperatures by moderately enhancing the degree of MVB. The stabilization of the metastable rhombohedral phase generates an optimized bandgap, sharpened valence band edge, and stimulative band convergence compared to stable phases. This leads to decent carrier concentration, improved carrier mobility, and enhanced density‐of‐state effective mass, culminating in a superior power factor. Moreover, lattice thermal conductivity is suppressed by pronounced lattice anharmonicity, low sound velocity, and strong phonon scattering induced by multiple defects. Consequently, a maximum zT of 1.0 at 773 K is achieved in (Ge 0.98 Pb 0.02 Se) 0.875 (AgInTe 2 ) 0.125 , resulting in a maximum energy conversion efficiency of 4.90% under the temperature difference of 500 K. This work underscores the significance of regulating MVB to stabilize metastable phases in chalcogenides.
Objectives: Cervical cancer is the fourth leading cause of cancer death among women worldwide. In currently, aberrant methylation of PAX1 is found in variety of solid tumors, including cervical ...cancer. In addition, the role of PAX1 gene methylation in cervical cancer and precancerous lesions screening has been confirmed in previous study. Here, we evaluated the predictive value of PAX1 methylation in concurrent chemo-radiotherapy (CCRT) outcomes in cervical cancer. Methods: This study enrolled 82 cervical cancer patients from August 2018 to August 2020. We compared the clinical results between different PAX1 methylation status. Hyper-methylation patients were subjects to MRI and quantitative methylation-specific PCR (QMSP) for PAX1 before, in the middle, immediately after, 1 month and 3 months after CCRT. The changes in PAX1 methylation during CCRT were analyzed. Results: The lower PAX1 methylation status were related to a poor tumor response. Based on the MRI findings three months post-treatment, the hypermethylated patients were classified into the complete response (CR; n=50) and partial remission (PR; n=18) groups. The average PAX1 △Cp value of CR and PR groups before radiotherapy was 5.08±1.98 and 4.32±2.00 respectively, and after concurrent chemo-radiotherapy was significantly increased to 17.35±4.96 and 16.99±6.17, respectively (P< 0.05). Furthermore, the PAX1 △Cp value between CR and PR groups were significantly different at mid-treatment and performed well in predicting short-term efficacy (AUC 0.84) in this period, and its sensitivity and specificity for predicting PR were 0.72 and 0.88, respectively. Conclusion: The PAX1 methylation level may predict the sensitivity and efficacy of CCRT in cervical cancer.
Wound healing has been a persistent clinical challenge for a long time. Electrical stimulation is an effective therapy with the potential to accelerate wound healing. In this work, the self-powered ...electrospun nanofiber membranes (triples) were constructed as multifunctional wound dressings with electrical stimulation and biochemical capabilities. Triple was composed of a hydrolyzable inner layer with antiseptic and hemostatic chitosan, a hydrophilic core layer loaded with conductive AgNWs, and a hydrophobic outer layer fabricated by self-powered PVDF. Triple exhibited presentable wettability and acceptable moisture permeability. Electrical performance tests indicated that triple can transmit electrical signals formed by the piezoelectric effect to the wound. High antibacterial activities were observed for triple against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, with inhibition rates of 96.52, 98.63, and 97.26%, respectively. In vitro cell assays demonstrated that triple cells showed satisfactory proliferation and mobility. A whole blood clotting test showed that triple can enhance hemostasis. The innovative self-powered multifunctional fibers presented in this work offer a promising approach to addressing complications and expediting the promotion of chronic wound healing.
The aim of this study was to determine whether incorporating qualitative parameters of contrast-enhanced ultrasound (CEUS) can increase the accuracy of adnexal lesion assessments with Ovarian-Adnexal ...Reporting and Data System (O-RADS) ultrasound category 4 or 5.
Retrospective analysis of patients with adnexal masses who underwent conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS) examinations between January and August of 2020. The study investigators reviewed and analyzed the morphological features of each mass before categorizing the US images independently according to the O-RADS system published by the American College of Radiology. In the CEUS analysis, the initial time and intensity of enhancement involving the wall and/or septation of the mass were compared with the uterine myometrium. Internal components of each mass were observed for signs of enhancement. The sensitivity, specificity, and Youden's index were calculated as the contrast variables and O-RADS.
Receiver operating characteristic curve analysis revealed that the best cutoff value was higher than O-RADS 4. When information on the extent of enhancement was applied to selectively upgrade O-RADS category 4 and selectively downgrade O-RADS category 5, the overall sensitivity increased to 90.2%, while the level of specificity (91.3%) remained the same.
Incorporating additional information from CEUS with respect to the extent of enhancement helped to improve the sensitivity of O-RADS category 4 and 5 masses without loss of specificity.
•Erosion profoundly affected the contents of humus fractions and Fe/Al oxides in different size fractions of soil aggregates.•Interactions between SOM components and Fe/Al oxides are crucial for ...aggregate stability.•Organic-inorganic cementing materials jointly contribute to aggregate stability.•FA, Feo and Ald are the primary contributors to aggregate stability.
Water erosion considerably affects the stability and particle size distribution of soil aggregates, but the underlying mechanisms of water erosion remain unclear. To this end, we selected four landscape positions (top-, up-, mid-, and toe-slope) with distinct erosion and deposition characteristics on a typical eroded slope in southern China to conduct experiments- aiming to investigate the main drivers of soil aggregate stability during erosion and deposition processes. Soil samples were collected from 12 sites, and 4 size classes (>2, 2–0.25, 0.25–0.053, and <0.053 mm) of soil aggregates were obtained using the wet sieving method. The composition and stability of the soil aggregates, as well as the contents of organic (organic matter components) and inorganic (iron-aluminum oxides) cementing materials of different particle sizes, were determined. The results indicated that erosion significantly reduced the aggregate stability and the >0.25 mm water-stable aggregate content (WR0.25) (P < 0.05). The mean weight diameter (MWD) and geometric mean diameter (GMD) values of the soil aggregates at the eroding site decreased, and the fractal dimension (FD) increased. Furthermore, erosion markedly reduced the humic acid (HA) and fulvic acid (FA) contents in the bulk soils and soil aggregates, while the HA content showed no obvious difference between the eroding and depositional sites. In addition to the presence of complexed iron/alumina oxides (Fep/Alp), erosion markedly reduced the contents of amorphous (Feo/Alo) and free-form (Fed/Ald) iron/alumina oxides in the bulk soils and size fractions. Moreover, Fed/Ald, Fep and Feo/Alo were present in the microaggregates, while Alp was found in the macroaggregates. Additionally, boosted regression tree (BRT) analysis indicated that FA (36.70 %), Feo (19.00 %), and Ald (12.71 %) were the crucial predictors of soil aggregate stability. These findings further confirm that the organic and inorganic cementing materials in red soils collectively contribute to aggregate stabilization under the impact of erosion. This study facilitates a deeper understanding of the mechanisms governing soil aggregate stability in eroded landscapes, and provides a theoretical basis for biogeochemical cycling processes.
PDF
