Granzymes expression patterns predict immunotherapy response and identify the heterogeneity of CD8+ T cell subsets.

BACKGROUND: Recent studies illustrated the effects of granzymes (GZMs) gene alterations on immunotherapy response of cancer patients. Thus, we aimed to systematically analyze the expression and prognostic value of GZMs for immunotherapy in different cancers, and identified heterogeneity of the GZMs expression-based CD8+ T cell subsets. METHODS: First, we analyzed GZMs expression and prognostic value at pan-cancer level. Meanwhile, we established a GZMs score by using the single-sample gene set enrichment analysis (ssGSEA) algorithm to calculate the enrichment scores (ES) based on a gene set of five GZMs. The potential value of GZMs score for predicting survival and immunotherapy response was evaluated using the tumor immune dysfunction and exclusion (TIDE) and immunophenoscore (IPS) algorithm, and we validated it in immunotherapy cohorts. CellChat, scMetabolism, and SCENIC R packages were used for intercellular communication networks, quantifying metabolism activity, and regulatory network reconstruction, respectively. RESULTS: The GZMs score was significantly associated with IPS, TIDE score. Patients with high GZMs score tended to have higher objective response rates of immunotherapy in melanoma and urothelial carcinoma. GZMs expression-based CD8+ T cell subsets presented heterogeneity in functions, metabolism, intercellular communications, and the tissue-resident memory programs in lung adenocarcinoma (LUAD). The transcription factors RUNX3 and ETS1, which may regulate the expression of GZMs, was found to be positively correlated with the tissue-resident memory T cells-related marker genes. CONCLUSIONS: The higher GZMs score may indicate better response and overall survival (OS) outcome for immunotherapy in melanoma and urothelial carcinoma but worse OS in renal cell carcinoma (RCC). The GZMs score is a potential prognostic biomarker of diverse cancers. RUNX3 and ETS1 may be the potential targets to regulate the infiltration of GZMs expression-based CD8+ T cell subsets and affect the tissue-resident memory programs in LUAD, which may affect the prognosis of LUAD patients and the response to immunotherapy.

Advancement and Applications of Nanotherapy for Cancer Immune Microenvironment.

Cancer treatment has evolved rapidly due to major advances in tumor immunity research. However, due to the complexity, heterogeneity, and immunosuppressive microenvironment of tumors, the overall efficacy of immunotherapy is only 20%. In recent years, nanoparticles have attracted more attention in the field of cancer immunotherapy because of their remarkable advantages in biocompatibility, precise targeting, and controlled drug delivery. However, the clinical application of nanomedicine also faces many problems concerning biological safety, and the synergistic mechanism of nano-drugs with immunity remains to be elucidated. Our study summarizes the functional characteristics and regulatory mechanisms of nanoparticles in the cancer immune microenvironment and how nanoparticles activate and long-term stimulate innate immunity and adaptive immunity. Finally, the current problems and future development trends regarding the application of nanoparticles are fully discussed and prospected to promote the transformation and application of nanomedicine used in cancer treatment.

Integrated transcriptome and proteome analysis provides new insights into camptothecin biosynthesis and regulation in Camptotheca acuminata.

Camptotheca acuminata Decne., the main source of camptothecin (CPT), has received increasing attention for its remarkable antitumor activity. Many CPT derivatives are clinically used as effective anticancer agents worldwide. However, their biosynthesis mechanism remains unclear, and uncovering this pathway would greatly facilitate development of alternative CPT production methods to replace current inefficient plant-derived ones. The expression of >30,000 genes was accurately quantified using unique molecular identifier RNA sequencing in 10 C. acuminata tissues, and 7854 proteins from five tissues were quantified with label-free quantitative proteomics. Fifteen full-length transcriptomes were sequenced with long-read Oxford Nanopore Technologies, and 5692 alternative splicing events were discovered among 4746 genes. Integrated transcriptome and proteome analysis provided novel insights into CPT biosynthesis and its hierarchical regulation. Five cytochrome P450s and three O-methyltransferases were considered as candidates involved in the biosynthesis of CPT and its derivatives, while 15 transcription factors potentially regulating CPT biosynthesis were screened. These findings provide important clues for elucidating the biosynthetic mechanisms of CPT and its derivatives and substantially contribute to the future production of these anticancer agents with synthetic biology. The generated large-scale multiomics data also provide valuable resources for investigating the functional genomics of the most important CPT-producing plant species-C. acuminata.

MRI-measured periprostatic adipose tissue volume as a prognostic predictor in prostate cancer patients undergoing laparoscopic radical prostatectomy.

In this study, we evaluated the association between the PPAT volume and the prognosis of PCa patients after LRP. We retrospectively analysed data of 189 PCa patients who underwent LRP in Beijing Chaoyang Hospital. Volumes of PPAT and prostate were measured by magnetic resonance imaging (MRI), and normalized PPAT volume was computed (PPAT volume divided by prostate volume). Patients were then stratified into the high-PPAT group (n = 95) and low-PPAT group (n = 94) by the median of normalized PPAT volume (73%). The high-PPAT group had significantly higher Gleason score (total score 8 or more, 39.0% vs. 4.3%, p < 0.001) and pathological stage (stage T3b, 28.4% vs. 13.8%, p = 0.048). No significant correlation between normalized PPAT volume and body mass index (ρ = -0.012, p = 0.872) was observed. Kaplan-Meier curve analysis showed the high-PPAT group had significantly shorter biochemical recurrence (BCR) interval (median progression-free survival time 15.9 months vs. 32.7 months, p = 0.001). Univiarate and multivariate Cox regression analyses showed high normalized PPAT volume (>73%) (hazard ratio 1.787 [1.075-3.156], p = 0.002) were independent risk factors for BCR post-operatively. In conclusion, MRI-measured PPAT volume is of significant prognostic value for PCa patients undergoing LRP.

Single-cell RNA sequencing provides a high-resolution roadmap for understanding the multicellular compartmentation of specialized metabolism.

Monoterpenoid indole alkaloids (MIAs) are among the most diverse specialized metabolites in plants and are of great pharmaceutical importance. We leveraged single-cell transcriptomics to explore the spatial organization of MIA metabolism in Catharanthus roseus leaves, and the transcripts of 20 MIA genes were first localized, updating the model of MIA biosynthesis. The MIA pathway was partitioned into three cell types, consistent with the results from RNA in situ hybridization experiments. Several candidate transporters were predicted to be essential players shuttling MIA intermediates between inter- and intracellular compartments, supplying potential targets to increase the overall yields of desirable MIAs in native plants or heterologous hosts through metabolic engineering and synthetic biology. This work provides not only a universal roadmap for elucidating the spatiotemporal distribution of biological processes at single-cell resolution, but also abundant cellular and genetic resources for further investigation of the higher-order organization of MIA biosynthesis, transport and storage.

MRI-measured adipose features as predictive factors for detection of prostate cancer in males undergoing systematic prostate biopsy: a retrospective study based on a Chinese population.

In this study, we retrospectively evaluated the data of 901 men undergoing ultrasonography-guided systematic prostate biopsy between March 2013 and May 2022. Adipose features, including periprostatic adipose tissue (PPAT) thickness and subcutaneous fat thickness, were measured using MRI before biopsy. Prediction models of all PCa and clinically significant PCa (csPCa) (Gleason score higher than 6) were established based on variables selected by multivariate logistic regression and prediction nomograms were constructed. Patients with PCa had higher PPAT thickness (4.64 [3.65-5.86] vs. 3.54 [2.49-4.51] mm, p < 0.001) and subcutaneous fat thickness (29.19 [23.05-35.95] vs. 27.90 [21.43-33.93] mm, p = 0.013) than those without PCa. Patients with csPCa had higher PPAT thickness (4.78 [3.80-5.88] vs. 4.52 [3.80-5.63] mm, p = 0.041) than those with non-csPCa. Adding adipose features to the prediction models significantly increased the area under the receiver operating characteristics curve for the prediction of all PCa (0.850 vs. 0.819, p < 0.001) and csPCa (0.827 vs. 0.798, p < 0.001). Based on MRI-measured adipose features and clinical parameters, we established two nomograms that were simple to use and could improve patient selection for prostate biopsy in Chinese population.

Bioinformatic and Experimental Analyses Reveal That KIF4A Is a Biomarker of Therapeutic Sensitivity and Predicts Prognosis in Cervical Cancer Patients.

OBJECTIVE: This study aims to investigate the expression, prognostic value, and function of kinesin superfamily 4A (KIF4A) in cervical cancer. METHODS: Cervical cancer cell lines (Hela and SiHa) and TCGA data were used for experimental and bioinformatic analyses. Overall survival (OS) and progression free survival (PFS) were compared between patients with high or low KIF4A expression. Copy number variation (CNV) and somatic mutations of patients were visualized and GISTIC 2.0 was used to identify significantly altered sites. The function of KIF4A was also explored based on transcriptome analysis and validated by experimental methods. Chemotherapeutic and immunotherapeutic benefits were inferred using multiple reference databases and algorithms. RESULTS: Patients with high KIF4A expression had better OS and PFS. KIF4A could inhibit proliferation and migration and induce G1 arrest of cervical cancer cells. Higher CNV load was observed in patients with low KIF4A expression, while the group with low KIF4A expression displayed more significantly altered sites. A total of 13 genes were found to mutate more in the low KIF4A expression group, including NOTCH1 and PUM1. The analysis revealed that low KIF4A expression may indicate an immune escape phenotype, and patients in this group may benefit more from immunotherapy. With respect to chemotherapy, cisplatin and gemcitabine may respond better in patients with high KIF4A expression, while 5-fluorouracil etc. may be responded better in patients with low KIF4A expression CONCLUSION: KIF4A is a tumor suppressor gene in cervical cancer, and it can be used as a prognostic and therapeutic biomarker in cervical cancer.

The design of a high-voltage, long-pulse width, flat-top compensation pulse generator based on metal oxide varistors.

In recent years, the pulse forming technology based on metal oxide varistors (MOVs) has been verified to be an effective way to generate high-voltage quasi-square pulses. Due to the limited varistor voltage of a single MOV brick, multiple MOV bricks connected in series are required to stabilize a pulse with high amplitude (larger than hundreds of kV), which leads to the rise of the series inductance of the MOV branch and the flat-top droop in the output waveform. This paper provides two solutions to reduce the influence of the MOV branch inductance on output waveforms. One is that a coaxial evolute structure of the MOV bricks connected in series is designed, which can not only improve the insulation capacity but also reduce the branch inductance. Another is that a flat-top compensation scheme named "PFN-MOV" (Pulse Forming Network) is proposed, which adds an LC filtering branch to shape the signal into a flat-top rising wave with ripple and then offsets the flat-top droop caused by the inductance of the MOV branch. Based on the above ideas, a high-voltage, long-pulse width, flat-top compensation pulse generator is designed and tested, and a quasi-square pulse with voltage amplitude of more than 500 kV, pulse width greater than 800 ns, rise time of less than 50 ns, and flat top of about 600 ns is obtained experimentally. This MOV based generator has the advantage of simple design, compact construction, and better flat top, which is promising to be used as a compact long-pulse driver in many fields, such as high-current accelerator, industrial dedusting, medical sterilization, and cancer treatment.

A battery-powered over-voltage triggering method for two-electrode spark gaps in Marx generator.

Triggered gas switches with trigger electrodes, such as three-electrode spark switches and trigatron type spark switches, have been widely used in repetitive operating Marx generators due to their large current flowing capability. However, the ablation of trigger electrodes during repetitive operation is inevitable, which reduces the working life of triggered gas switches. In this paper, we introduced an over-voltage triggering method for two-electrode spark switches by replacing one of the charging inductors of the Marx generator with a pulse generator. The experimental results showed that a high-voltage trigger pulse with an amplitude of 60 kV and a rising speed of 7.65 kV/100 ns was obtained from a single stackable module with a 12 V lithium battery pack as the energy source. Due to the absence of trigger electrodes, the triggering method is beneficial to extend the lifetime of switches and realize a maintenance-free repetitive operating Marx generator.

Guanylate-Binding Protein 1 as a Potential Predictor of Immunotherapy: A Pan-Cancer Analysis.

Background: Mainstream application of cancer immunotherapy is hampered by the low response rate of most cancer patients. A novel immunotherapeutic target or a biomarker predicting response to immunotherapy needs to be developed. Guanylate-binding protein 1 (GBP1) is an interferon (IFN)-inducible guanosine triphosphatases (GTPases) involving inflammation and infection. However, the immunological effects of GBP1 in pan-cancer patients are still obscure. Methods: Using large-scale public data, we delineated the landscape of GBP1 across 33 cancer types. The correlation between GBP1 expression or mutation and immune cell infiltration was estimated by ESTIMATE, TIMER, xCell, and quanTIseq algorithms. GBP1-related genes and proteins were subjected to function enrichment analysis. Clustering analysis explored the relationship between GBP1 expression and anti-tumor immune phenotypes. We assessed the patient's response to immunotherapy using the tumor immune dysfunction and exclusion (TIDE) score and immunophenoscore (IPS). Furthermore, we validated the predictive power of GBP1 expression in four independent immunotherapy cohorts. Results: GBP1 was differentially expressed in tumors and normal tissues in multiple cancer types. Distinct correlations existed between GBP1 expression and prognosis in cancer patients. GBP1 expression and mutation were positively associated with immune cell infiltration. Function enrichment analysis showed that GBP1-related genes were enriched in immune-related pathways. Positive correlations were also observed between GBP1 expression and the expression of immune checkpoints, as well as tumor mutation burden (TMB). Pan-cancer patients with higher GBP1 expression were more inclined to display "hot" anti-tumor immune phenotypes and had lower TIDE scores and higher immunophenoscore, suggesting that these patients had better responses to immunotherapy. Patients with higher GBP1 expression exhibited improved overall survival and clinical benefits in immunotherapy cohorts, including the Gide et al. cohort [area under the curve (AUC): 0.813], the IMvigor210 cohort (AUC: 0.607), the Lauss et al. cohort (AUC: 0.740), and the Kim et al. cohort (AUC: 0.793). Conclusion: This study provides comprehensive insights into the role of GBP1 in a pan-cancer manner. We identify GBP1 expression as a predictive biomarker for immunotherapy, potentially enabling more precise and personalized immunotherapeutic strategies in the future.

BACH1: A Potential Predictor of Survival in Early-Stage Lung Adenocarcinoma.

PURPOSE: Recent researches showed the vital role of BACH1 in promoting the metastasis of lung cancer. We aimed to explore the value of BACH1 in predicting the overall survival (OS) of early-stage (stages I-II) lung adenocarcinoma. Patients and Methods. Lung adenocarcinoma cases were screened from the Cancer Genome Atlas (TCGA) database. Functional enrichment analysis was performed to obtain the biological mechanisms of BACH1. Gene set enrichment analysis (GSEA) was performed to identify the difference of biological pathways between high- and low-BACH1 groups. Univariate and multivariate COX regression analysis had been used to screen prognostic factors, which were used to establish the BACH1 expression-based prognostic model in the TCGA dataset. The C-index and time-dependent AUC curve were used to evaluate predictive power of the model. External validation of prognostic value was performed in two independent datasets from Gene Expression Omnibus (GEO). Decision analysis curve was finally used to evaluate clinical usefulness of the BACH1-based model beyond pathologic stage alone. RESULTS: BACH1 was an independent prognostic factor for lung adenocarcinoma. High-expression BACH1 cases had worse OS. BACH1-based prognostic model showed an ideal C-index and t-AUC and validated by two GEO datasets, independently. More importantly, the BACH1-based model indicated positive clinical applicability by DCA curves. CONCLUSION: Our research confirmed that BACH1 was an important predictor of prognosis in early-stage lung adenocarcinoma. The higher the expression of BACH1, the worse OS of the patients.

Influence of climates and materials on the moisture buffering in office buildings: a comprehensive numerical study in China.

In recent years, moisture buffering materials for interior finishing have received much attention for their ability to regulate indoor humidity passively. It is necessary to investigate the potential of such materials' moisture buffering performance before application because the effect is highly climate and material dependent. However, existing studies in China lack a comprehensive overview of the moisture buffering potential of different interior finishing materials throughout the large country with a wide spectrum of climates. This paper aims to outline the moisture buffering potential for office buildings in various climates in China through numerical methods. Specifically, simulations in 15 representative Chinese cities are conducted with five interior finishing materials under two heating, ventilation, and air conditioning (HVAC) scenarios. The results show that the moisture buffering materials hold a general potential to regulate indoor humidity conditions and reduce buildings' HVAC load. Such benefits are evident in the mild climate but weak in humid areas. The moisture buffering effect also displays significant seasonal variations and could worsen indoor humidity conditions in some cases, indicating the importance of utilizing moisture buffering materials properly. In addition, although moisture buffering materials can reduce the HVAC load, the reduction is limited, within 3 kWh/m2, in most simulated cases. The energy-saving benefits of moisture buffering materials should thus not be over-emphasized. Finally, suggestions are put forward to instruct the choice of interior finishing material according to climate and buildings' HVAC scenarios.

Diagnostic performance of MR black-blood thrombus imaging for cerebral venous thrombosis in real-world clinical practice.

OBJECTIVES: MR black-blood thrombus imaging (BTI) has been developed for the detection of cerebral venous thrombosis (CVT). Yet, there is a lack of real-world data to verifying its clinical performance. This study aims to evaluate the performance of BTI in diagnosing and staging CVT in a 5-year period. METHODS: Patients suspected of CVT were enrolled between 2014 and 2019. Patients with or without BTI scans were classified into group A and group B, respectively. The prevalence of correct diagnosis of CVT and patients with evaluable clot age were compared. The diagnostic performance of BTI including sensitivity, specificity, and specific staging information was further analyzed. RESULTS: Two hundred and twenty-one of the 308 patients suspected of CVT were eligible in the current study (114 in group A and 97 in group B), with 125 diagnosed by multidisciplinary teams to have CVTs (56 in group A, 69 in group B). The rate of correct diagnosis of CVT was higher in group A than that in group B (94.7% vs 60.8%, p < 0.001, x2 = 36.517) after adding BTI images. The percent of patients with evaluable staged segments between the two groups were 96.4% and 33.9%, respectively (x2 = 48.191, p < 0.001). BTI showed a sensitivity of 96.4% and 87.9% in the detection of CVT on per-patient and per-segment level, respectively. Up to 98.1% of all thrombosed segments could be staged by BTI and 59.6% of them were matched with clinical staging. CONCLUSIONS: In the actual clinical practice, BTI improves diagnostic confidence and has an excellent performance in confirming and staging CVT. KEY POINTS: • Black-blood thrombus imaging has good diagnostic performance in detecting cerebral venous thrombosis compared to traditional imaging methods with strong evidence in the actual clinical setting. • BTI helps clinicians to diagnose CVT with more accuracy and confidence, which can be served as a promising imaging examination. • BTI can also provide additional information of different thrombus ages objectively, the valuable reference for clinical strategy.

Postoperative Radiotherapy for Patients With Resectable Stage III-N2 Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

PURPOSE: For resectable cases of stage III-N2 non-small cell lung cancer (NSCLC), the best treatment after surgery is still uncertain. The effect of postoperative radiotherapy (PORT) is controversial. Thus, we performed this updated meta-analysis to reassess the data of PORT in stage III-N2 NSCLC patients, to figure out whether these patients can benefit from PORT. METHODS: We conducted searches of the published literature in EMBASE, PubMed, and the Cochrane Library for relevant randomized control trials (RCTs) comparing PORT group with the non-PORT group in NSCLC patients at stage III-N2. These studies allowed the prior chemotherapy in the treatment. We extracted the data from these articles and used the hazard ratios (HRs) and their 95% confidence intervals (CIs) as summary statistics for estimating the effect of PORT on overall survival (OS), disease-free survival (DFS), local-regional recurrence-free survival (LRFS). RESULT: The analyses of seven randomized controlled trials (1,318 participants) show no benefit of PORT on survival (HR, 0.87; 95% CI, 0.71 to 1.07; p = 0.18) but a significantly different effect of PORT on DFS (HR, 0.83; 95% CI, 0.71 to 0.97; p = 0.02) and LRFS (HR, 0.64; 95% CI, 0.50 to 0.81; p = 0.0003). There is not enough evidence of a difference in the effect on survival by the utility of chemotherapy along with PORT though subgroup analysis of no chemotherapy group, concurrent chemoradiotherapy and sequential chemoradiotherapy group. Even in trials with 3D-CRT radiation technique, the pooled analysis shows no benefit of PORT on survival in patients with stage III-N2 NSCLC (data is not shown). CONCLUSION: Our findings illustrate that in the postoperative treatment for patients with stage III-N2 NSCLC, PORT contributes to a significantly increased DFS and LR and may not associate with an improved OS, indicating a cautious selection.

Oncolytic Adenovirus: Prospects for Cancer Immunotherapy.

Immunotherapy has moved to the forefront of modern oncologic treatment in the past few decades. Various forms of immunotherapy currently are emerging, including oncolytic viruses. In this therapy, viruses are engineered to selectively propagate in tumor cells and reduce toxicity for non-neoplastic tissues. Adenovirus is one of the most frequently employed oncolytic viruses because of its capacity in tumor cell lysis and immune response stimulation. Upregulation of immunostimulatory signals induced by oncolytic adenoviruses (OAds) might significantly remove local immune suppression and amplify antitumor immune responses. Existing genetic engineering technology allows us to design OAds with increasingly better tumor tropism, selectivity, and antitumor efficacy. Several promising strategies to modify the genome of OAds have been applied: capsid modifications, small deletions in the pivotal viral genes, insertion of tumor-specific promoters, and addition of immunostimulatory transgenes. OAds armed with tumor-associated antigen (TAA) transgenes as cancer vaccines provide additional therapeutic strategies to trigger tumor-specific immunity. Furthermore, the combination of OAds and immune checkpoint inhibitors (ICIs) increases clinical benefit as evidence shown in completed and ongoing clinical trials, especially in the combination of OAds with antiprogrammed death 1/programed death ligand 1 (PD-1/PD-L1) therapy. Despite remarkable antitumor potency, oncolytic adenovirus immunotherapy is confronted with tough challenges such as antiviral immune response and obstruction of tumor microenvironment (TME). In this review, we focus on genomic modification strategies of oncolytic adenoviruses and applications of OAds in cancer immunotherapy.

Dynamics Modeling and Experimental Investigation of Gear Mechanism with Coupled Small Clearances.

Internal gear mechanism is widely used in micro-nano satellites due to its compact structure and high precision transmission. However, the vibration coupling caused by the small clearance coupling is more obvious and cannot be ignored under low speed, light load and zero gravity conditions. Based on the geometric relationship between radial clearance and backlash, a coupled model between dynamic backlash and radial clearance of internal meshing gear is established. Based on the conformal contact theory, the radial collision force model of the gear shaft and shaft sleeve considering the small clearances is established. Additionally, a multi-clearance gear rotor system test device is built to measure the vibration acceleration of the internal gear rotor system by an acceleration sensor and transmitted to the industrial computer through a signal collector for data processing. Through the comparison of simulation and experiment, the accuracy of the gear dynamics model is verified. The analysis results show that, compared with the traditional model, the calculation results of the gear mechanism model considering the small clearance coupling is closer to the experimental data.

A risk model developed based on tumor microenvironment predicts overall survival and associates with tumor immunity of patients with lung adenocarcinoma.

Tumor microenvironment (TME) has been reported to exhibit a crucial effect in lung cancer. Therefore, this study was aimed to investigate the genes associated with TME and develop a risk score to predict the overall survival (OS) of patients with lung adenocarcinoma (LUAD) based on these genes. The immune and stromal scores were generated by the ESTIMATE algorithm for LUAD patients in The Cancer Genome Atlas (TCGA) database. Differentially expressed gene and weighted gene co-expression network analyses were used to derive immune- and stromal-related genes. The Least Absolute Shrinkage and Selection Operator (LASSO)-Cox regression was applied for further selection and the selected genes were inputted into stepwise regression to develop TME-related risk score (TMErisk) which was further validated in Gene Expression Omnibus (GEO) datasets. TMErisk-related biological phenotypes were analyzed in function enrichment, tumor immune signature, and tumor mutation signature. The patient's response to immunotherapy was inferred by the tumor immune dysfunction and exclusion (TIDE) score and immunophenoscore (IPS). According to our results, TMErisk was developed based on SERPINE1, CX3CR1, CD200R1, GBP1, IRF1, STAP1, LOX, and OR7E47P. Furthermore, high TMErisk was identified as a poor factor for OS in TCGA and GEO datasets, as well as in subgroup analysis with different gender, smoking status, age, race, anatomic site, therapies, and tumor-node-metastasis (TNM) stages. Higher TMErisk is also associated negatively with the abundance of B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and other stromal or immune cells. Several genes of the human leukocyte antigen (HLA) family and immune checkpoints were less expressed in the high-TMErisk group. Mutations of 19 genes occurred more frequently in the high-TMErisk group. These mutations may be associated with TME change and indicate patients' response to immunotherapy. According to our analyses, a lower TMErisk score may indicate better response and OS outcome of immunotherapy.

Individualized model for predicting COVID-19 deterioration in patients with cancer: A multicenter retrospective study.

The 2019 novel coronavirus has spread rapidly around the world. Cancer patients seem to be more susceptible to infection and disease deterioration, but the factors affecting the deterioration remain unclear. We aimed to develop an individualized model for prediction of coronavirus disease (COVID-19) deterioration in cancer patients. The clinical data of 276 cancer patients diagnosed with COVID-19 in 33 designated hospitals of Hubei, China from December 21, 2019 to March 18, 2020, were collected and randomly divided into a training and a validation cohort by a ratio of 2:1. Cox stepwise regression analysis was carried out to select prognostic factors. The prediction model was developed in the training cohort. The predictive accuracy of the model was quantified by C-index and time-dependent area under the receiver operating characteristic curve (t-AUC). Internal validation was assessed by the validation cohort. Risk stratification based on the model was carried out. Decision curve analysis (DCA) were used to evaluate the clinical usefulness of the model. We found age, cancer type, computed tomography baseline image features (ground glass opacity and consolidation), laboratory findings (lymphocyte count, serum levels of C-reactive protein, aspartate aminotransferase, direct bilirubin, urea, and d-dimer) were significantly associated with symptomatic deterioration. The C-index of the model was 0.755 in the training cohort and 0.779 in the validation cohort. The t-AUC values were above 0.7 within 8 weeks both in the training and validation cohorts. Patients were divided into two risk groups based on the nomogram: low-risk (total points ≤ 9.98) and high-risk (total points > 9.98) group. The Kaplan-Meier deterioration-free survival of COVID-19 curves presented significant discrimination between the two risk groups in both training and validation cohorts. The model indicated good clinical applicability by DCA curves. This study presents an individualized nomogram model to individually predict the possibility of symptomatic deterioration of COVID-19 in patients with cancer.

Assessment of transportation processes of polyacrylamide in chernozem and saline soil by numerical model.

Polyacrylamide (PAM) was studied in two characteristic soils in Daqing City: chernozem and saline soil. 120 mg L-1 of KBr was used as a conservation tracer to estimate diffusion coefficients and pore velocities of chernozem and saline soil by using the breakthrough curves (BTCs) of Br-. Isothermal adsorption equations were coupled with the traditional two-site model to establish the transportation equation of PAM. The results of comparing the simulation curve with the BTCs of PAM at different rates showed that the transportation equation of PAM could simulate the transport process of PAM in soil column accurately. PAM behaved as non-equilibrium adsorption in both soils by calculating the kinetic parameters in this equation. The results of this work not only confirmed the kinetic parameters of PAM in both soils, but also found that there is a good liner relationship between the mass transfer coefficient and pore velocity. The R2 values of the two linear equations are 0.983 and 0.979. These linear equations provide a good prediction basis for site prediction. In addition, it was found that organic matter is the main influence factor for the adsorption capacity of chernozem causing significantly larger than that of saline soil.

Prognostic nomogram for predicting survival in patients with high grade endometrial stromal sarcoma: a Surveillance Epidemiology, and End Results database analysis.

OBJECTIVE: High grade endometrial stromal sarcoma is a rare and highly malignant tumor that lacks a prognostic model. The aim of this study was to develop a prognostic nomogram predicting the overall survival of patients with high grade endometrial stromal sarcoma. METHODS: Clinical data for patients were derived from the Surveillance Epidemiology, and End Results database. Cox analysis and Akaike's information criterion were used to construct the nomogram. The concordance index, time dependent receiver operating characteristic curve, and calibration plot were used to evaluate the discriminative and calibrating capability. The net reclassification index, integrated discrimination improvement, and concordance index change were also compared between the nomogram and the International Federation of Gynecology and Obstetrics (FIGO) stage. Clinical benefit was evaluated using decision curve analysis. The patients were separated into groups with low and high nomogram risk scores. Kaplan-Meier curve analysis and Cox analysis were used to investigate the survival difference between the two groups. RESULTS: The training and validation cohorts had 461 and 195 patients, respectively. A nomogram that incorporated disease stage, age, surgery, lymph node status, radiotherapy, and chemotherapy for predicting overall survival was established and validated. The concordance index of the nomogram was 0.734 (0.708-0.761) in the training cohort and 0.705 (0.659-0.751) in the validation cohort. The calibration plots showed a favorable calibrating ability of the nomogram. The 1 year and 3 year time dependent receiver operating characteristic curves showed the better discriminative ability of the nomogram than the staging system. The concordance index change, net reclassification index, and integrated discrimination improvement also indicated a significantly (p<0.05) better predictive power of the nomogram over disease stage. Furthermore, decision curve analysis suggested that the nomogram was clinically useful and had a larger clinical net benefit than disease stage alone. Patients with a high risk score had distinctly poorer survival than those with low risk scores. CONCLUSIONS: A prognostic nomogram in patients with high grade endometrial stromal sarcoma exhibited favorable prognostic discrimination and survival prediction ability compared with FIGO stage.