A Multiple Attention Convolutional Neural Networks for Diesel Engine Fault Diagnosis.

Fault diagnosis can improve the safety and reliability of diesel engines. An end-to-end method based on a multi-attention convolutional neural network (MACNN) is proposed for accurate and efficient diesel engine fault diagnosis. By optimizing the arrangement and kernel size of the channel and spatial attention modules, the feature extraction capability is improved, and an improved convolutional block attention module (ICBAM) is obtained. Vibration signal features are acquired using a feature extraction model alternating between the convolutional neural network (CNN) and ICBAM. The feature map is recombined to reconstruct the sequence order information. Next, the self-attention mechanism (SAM) is applied to learn the recombined sequence features directly. A Swish activation function is introduced to solve "Dead ReLU" and improve the accuracy. A dynamic learning rate curve is designed to improve the convergence ability of the model. The diesel engine fault simulation experiment is carried out to simulate three kinds of fault types (abnormal valve clearance, abnormal rail pressure, and insufficient fuel supply), and each kind of fault varies in different degrees. The comparison results show that the accuracy of MACNN on the eight-class fault dataset at different speeds is more than 97%. The testing time of the MACNN is much less than the machine running time (for one work cycle). Therefore, the proposed end-to-end fault diagnosis method has a good application prospect.

The survival benefit of metastasectomy for metastatic non-clear cell renal cell carcinoma: a retrospective cohort study.

PURPOSE: The aim of this study was to explore the benefit the metastasectomy for patients with metastatic non-clear cell carcinoma (non-ccRCC). METHODS: This study enrolled 120 patients with confirmed metastatic non-ccRCC from the RCC database of our center from 2008 to 2021. Patients without metastasectomy were grouped as radical nephrectomy without metastasectomy patients. The clinical outcomes included overall survival (OS) and progression-free survival (PFS). Cox regression and Kaplan-Meier analyses were used to assess potential factors that predict clinical benefits from metastasectomy. RESULTS: A total of 100 patients received radical nephrectomy alone, while the remaining 20 patients underwent both radical nephrectomy and metastasectomy. There was no significant difference in age between the two groups. Out of 100 patients who underwent radical nephrectomy, 60 were male, and out of 20 patients who had both radical nephrectomy and metastasectomy, 12 were male. Patients who underwent systemic therapy plus radical nephrectomy and metastasectomy had significantly better PFS (27.1 vs. 14.0, p = 0.032) and OS (67.3 vs. 24.0, p = 0.043) than those who underwent systemic therapy plus radical nephrectomy alone. Furthermore, for patients without liver metastasis (n = 54), systemic therapy plus radical nephrectomy and metastasectomy improved both PFS (p = 0.028) and OS (p = 0.043). Similarly, for patients with metachronous metastasis, systemic therapy plus radical nephrectomy and metastasectomy improved both PFS (p = 0.043) and OS (p = 0.032). None of the patients experienced serious perioperative complications (Clavien-Dindo Classification ≥ III grade). CONCLUSION: Metastasectomy in patients with metastatic non-ccRCC may provide clinical benefits in terms of improved PFS and OS, especially in patients without liver metastasis and those with metachronous metastasis.

Predicting abiraterone efficacy in advanced prostate cancer: Insights from marker of proliferation Ki67.

BACKGROUND: KI67 is a well-known biomarker reflecting cell proliferation. We aim to elucidate the predictive role of KI67 in the efficacy of abiraterone for patients with advanced prostate cancer (PCa). METHODS: Clinicopathological data of 152 men with metastatic PCa, who received abiraterone therapy were retrospectively collected. The KI67 positivity was examined by immunohistochemistry using the prostate biopsy specimen. The predictive value of KI67 on the therapeutic efficacy of abiraterone was explored using Kaplan-Meier curve and Cox regression analysis. The endpoints included prostate-specific antigen (PSA) progression-free survival (PSA-PFS), radiographic PFS (rPFS), and overall survival (OS). RESULTS: In total, 85/152 (55.9%) and 67/152 (44.1%) cases, respectively, received abiraterone at metastatic hormone-sensitive (mHSPC) and castration-resistant PCa (mCRPC) stage. The median KI67 positivity was 20% (interquartile range: 10%-30%). Overall, KI67 rate was not correlated with PSA response. Notably, an elevated KI67-positive rate strongly correlated with unfavorable abiraterone efficacy, with KI67 ≥ 30% and KI67 ≥ 20% identified as the optimal cutoffs for prognosis differentiation in mHSPC (median PSA-PFS: 11.43 Mo vs. 26.43 Mo, p < 0.001; median rPFS: 16.63 Mo vs. 31.90 Mo, p = 0.003; median OS: 21.77 Mo vs. not reach, p = 0.005) and mCRPC (median PSA-PFS: 7.17 Mo vs. 12.20 Mo, p = 0.029; median rPFS: 11.67 Mo vs. 16.47 Mo, p = 0.012; median OS: 21.67 Mo vs. not reach, p = 0.073) patients, respectively. Multivariate analysis supported the independent predictive value of KI67 on abiraterone efficacy. In subgroup analysis, an elevated KI67 expression was consistently associated with unfavorable outcomes in the majority of subgroups. Furthermore, data from another cohort of 79 PCa patients with RNA information showed that those with KI67 RNA levels above the median had a significantly shorter OS than those below the median (17.71 vs. 30.72 Mo, p = 0.035). CONCLUSIONS: This study highlights KI67 positivity in prostate biopsy as a strong predictor of abiraterone efficacy in advanced PCa. These insights will assist clinicians in anticipating clinical outcomes and refining treatment decisions for PCa patients.

Prognostic significance of circulating tumor DNA in urothelial carcinoma: a systematic review and meta-analysis.

BACKGROUND: Circulating tumor DNA (ctDNA) has emerged as a non-invasive technique that provides valuable insights into molecular profiles and tumor disease management. This study aimed to evaluate the prognostic significance of circulating tumor DNA (ctDNA) in urothelial carcinoma (UC) through a systematic review and meta-analysis. METHODS: A comprehensive search was conducted in MEDLINE, EMBASE, and the Cochrane Library from the inception to December 2023. Studies investigating the prognostic value of ctDNA in UC were included. Hazard ratios (HRs) of disease-free survival (DFS) and overall survival (OS) were extracted. Overall meta-analysis and subgroup exploration stratified by metastatic status, ctDNA sampling time, treatment type, and detection method was performed using the R software (version 4.2.2). RESULTS: A total of sixteen studies with 1725 patients were included. Fourteen studies assessed the association between baseline ctDNA status and patient outcomes. Patients with elevated ctDNA levels exhibited significantly worse DFS (HR=6.26; 95% CI, 3.71-10.58, P<0.001) and OS (HR=4.23; 95% CI, 2.72-6.57, P<0.001) regardless of metastatic status, ctDNA sampling time, treatment type and detection methods. Six studies evaluated the prognostic value of ctDNA dynamics in UC. Patients who showed a decrease or clearance in ctDNA levels during treatment or observation demonstrated more favorable DFS (HR=0.26, 95% CI, 0.17-0.41, P<0.001) and OS (HR=0.21, 95% CI, 0.11-0.38, P<0.001) compared to those who did not. The association remained consistent across the subgroup analysis based on metastatic status and detection methods. In the immune checkpoint inhibitor-treated setting, both lower baseline ctDNA level and ctDNA decrease during the treatment were significantly associated with more favorable oncologic outcomes. Furthermore, specific gene mutations such as FGFR3 identified in ctDNA also demonstrated predictive value in UC patients. CONCLUSION: This meta-analysis demonstrates a strong association of ctDNA status and its dynamic change with survival outcomes in UC, suggesting substantial clinical utility of ctDNA testing in prognosis prediction and decision making in this setting.

Memory/active T cell activation is associated with immunotherapeutic response in fumarate hydratase-deficient renal cell carcinoma.

PURPOSE: Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a rare and lethal subtype of kidney cancer. However, the optimal treatments and molecular correlates of benefits for FH-deficient RCC are currently lacking. EXPERIMENTAL DESIGN: A total of 91 patients with FH-deficient RCC from 15 medical centers between 2009 and 2022 were enrolled in this study. Genomic and bulk RNA sequencing (RNA-seq) were performed on 88 and 45 untreated FH-deficient RCCs, respectively. Single-cell RNA-seq was performed to identify biomarkers for treatment response. Main outcomes included disease-free survival (DFS) for localized patients, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) for metastatic patients. RESULTS: In the localized setting, we found that a cell cycle progression signature enabled to predict disease progression. In the metastatic setting, first-line immune checkpoint inhibitor plus tyrosine kinase inhibitor (ICI+TKI) combination therapy showed satisfactory safety and was associated with a higher ORR (43.2% vs. 5.6%), apparently superior PFS (median PFS: 17.3 vs. 9.6 months, P=0.016) and OS (median OS: not reached vs. 25.7 months, P=0.005) over TKI monotherapy. Bulk and single-cell RNA-seq data revealed an enrichment of memory and effect T cells in responders to ICI plus TKI combination therapy. Furthermore, we identified a signature of memory and effect T cells that was associated with the effectiveness of ICI plus TKI combination therapy. CONCLUSIONS: ICI plus TKI combination therapy may represent a promising treatment option for metastatic FH-deficient RCC. A memory/active T cell-derived signature is associated with the efficacy of ICI+TKI but necessitates further validation.

A new technique of autologous bone grafting for open-wedge high tibial osteotomy.

Purpose: This study aimed to demonstrate the application of orthotopic bone flap transplantation with a fibula transplantation (OBFT-FT) in open-wedge high tibial osteotomy (OW-HTO) and to assess the effect of OBFT-FT on gap healing. Patients and methods: From January to July 2020, 18 patients who underwent OW-HTO with OBFT-FT were reviewed for this study. Demographics, postoperative complications, and radiological and clinical outcomes of patients were collected. Finally, the clinical outcomes of patients were analyzed. Results: A total of 14 patients were included in this study. The average age and body mass index were 59.6 ± 9.2 years and 28.1 ± 4.5 kg/m2, respectively. The average correction angle and gap width were 9.5 ± 1.8° and 10.2 ± 2.7 mm, respectively. The rates of radiological gap healing at sixth week, third month, and sixth month were 42.9%, 85.7%, and 100%, respectively. The mean Lysholm score, International Knee Documentation Committee score, and visual analog scale scores at sixth-month follow-up were significantly better than the preoperative scores (p < 0.001, p < 0.001, p = 0.001, respectively). And, no delayed union or non-union, collapse, loss of correction, or surgical site infection were found. Conclusions: As a new technique for autologous bone graft, the OBFT-FT could be successfully applied in the treatment of gap healing after OW-HTO, and excellent radiological and clinical outcomes could be seen on patients' short-term follow-up.

Development and validation of a nomogram for predicting in-hospital mortality of patients with cervical spine fractures without spinal cord injury.

BACKGROUND: The incidence of cervical spine fractures is increasing every day, causing a huge burden on society. This study aimed to develop and verify a nomogram to predict the in-hospital mortality of patients with cervical spine fractures without spinal cord injury. This could help clinicians understand the clinical outcome of such patients at an early stage and make appropriate decisions to improve their prognosis. METHODS: This study included 394 patients with cervical spine fractures from the Medical Information Mart for Intensive Care III database, and 40 clinical indicators of each patient on the first day of admission to the intensive care unit were collected. The independent risk factors were screened using the Least Absolute Shrinkage and Selection Operator regression analysis method, a multi-factor logistic regression model was established, nomograms were developed, and internal validation was performed. A receiver operating characteristic (ROC) curve was drawn, and the area under the ROC curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were calculated to evaluate the discrimination of the model. Moreover, the consistency between the actual probability and predicted probability was reflected using the calibration curve and Hosmer-Lemeshow (HL) test. A decision curve analysis (DCA) was performed, and the nomogram was compared with the scoring system commonly used in clinical practice to evaluate the clinical net benefit. RESULTS: The nomogram indicators included the systolic blood pressure, oxygen saturation, respiratory rate, bicarbonate, and simplified acute physiology score (SAPS) II. The results showed that our model had satisfactory predictive ability, with an AUC of 0.907 (95% confidence interval [CI] = 0.853-0.961) and 0.856 (95% CI = 0.746-0.967) in the training set and validation set, respectively. Compared with the SAPS-II system, the NRI values of the training and validation sets of our model were 0.543 (95% CI = 0.147-0.940) and 0.784 (95% CI = 0.282-1.286), respectively. The IDI values of the training and validation sets were 0.064 (95% CI = 0.004-0.123; P = 0.037) and 0.103 (95% CI = 0.002-0.203; P = 0.046), respectively. The calibration plot and HL test results confirmed that our model prediction results showed good agreement with the actual results, where the HL test values of the training and validation sets were P = 0.8 and P = 0.95, respectively. The DCA curve revealed that our model had better clinical net benefit than the SAPS-II system. CONCLUSION: We explored the in-hospital mortality of patients with cervical spine fractures without spinal cord injury and constructed a nomogram to predict their prognosis. This could help doctors assess the patient's status and implement interventions to improve prognosis accordingly.

Nanoconfinement boosts affinity of hydrated zirconium oxides to arsenate: Surface complexation modeling study.

Nanoscale hydrated zirconium oxide (HZO) holds great potential in groundwater purification due to its ability to form inner-sphere coordination with arsenate. Despite being frequently used, especially as encapsulations in host materials for practical application in water treatment, the adsorption mechanisms of solutes on HZO are not appropriately explored, in particular for arsenate adsorption. In this study, we investigated the Zr-As coordination configuration and identified the most credible Zr-As configuration using surface complexation modeling (SCM), XPS and FT-IR analysis. The corresponding intrinsic coordination constants (Kintr) values was calculated by SCM, and the nanoconfinement effects were distinguished by comparing bare HZO with the HZO nanoparticles (NPs) encapsulated inside the strongly basic anion exchanger D201. Potentiometric titration suggests that the surface Zirconium hydroxyl groups (≡ZrOH) mainly exist in protonated form (≡ZrOH2+). Batch adsorption experiments demonstrate that the D201 hosts could adsorb As(V) through ion exchange by the quaternary ammonium groups under the low ionic strength (≤0.01 M NaNO3) and at pH > 6. The nanocomposite (HZO@D201) exhibits a higher adsorption capacity in a wide range of pH (3-10) and ionic strength (0.001-0.1 M NaNO3) than bare HZO. SCM simulations reveal that the coordination configuration of diprotonated monodentate mononuclear (MM-H2) dominates at pH 3-6, while deprotonated bidentate binuclear (BB-H0) dominates at pH > 7. For each configuration, the intrinsic coordination constants (Kintr) of HZO@D201 (10-0.66 and 10-16.10, respectively) are significantly higher than those of bare HZO (10-12.24 and 10-44.42, respectively), indicating a superior chemical bonding affinity caused by nanoconfinement. The obtained Kintr values are used to predict arsenate adsorption isotherms in pH 3 and 9, and the results align with the SCM simulation outcomes. This study may offer a feasible method for investigating the nanoconfinement effect of emerging nanocomposite adsorbents from a thermodynamic perspective, and provide reference coordination equilibrium constants of HZO for research and practical application.

Genomic and Evolutionary Characterization of Concurrent Intraductal Carcinoma and Adenocarcinoma of the Prostate.

Intraductal carcinoma of the prostate (IDC-P) is a lethal prostate cancer subtype that generally coexists with invasive high-grade prostate acinar adenocarcinoma (PAC) but exhibits distinct biological features compared with concomitant adenocarcinoma. In this study, we performed whole-exome, RNA, and DNA-methylation sequencing of IDC-P, concurrent invasive high-grade PAC lesions, and adjacent normal prostate tissues isolated from 22 radical prostatectomy specimens. Three evolutionary patterns of concurrent IDC-P and PAC were identified: early divergent, late divergent, and clonally distant. In contrast to those with a late divergent evolutionary pattern, tumors with clonally distant and early divergent evolutionary patterns showed higher genomic, epigenomic, transcriptional, and pathologic heterogeneity between IDC-P and PAC. Compared with coexisting PAC, IDC-P displayed increased expression of adverse prognosis-associated genes. Survival analysis based on an independent cohort of 505 patients with metastatic prostate cancer revealed that IDC-P carriers with lower risk International Society of Urological Pathology (ISUP) grade 1-4 adenocarcinoma displayed a castration-resistant free survival as poor as those with the highest risk ISUP grade 5 tumors that lacked concurrent IDC-P. Furthermore, IDC-P exhibited robust cell-cycle progression and androgen receptor activities, characterized by an enrichment of cellular proliferation-associated master regulators and genes involved in intratumoral androgen biosynthesis. Overall, this study provides a molecular groundwork for the aggressive behavior of IDC-P and could help identify potential strategies to improve treatment of IDC-P. SIGNIFICANCE: The genomic, transcriptomic, and epigenomic characterization of concurrent intraductal carcinoma and adenocarcinoma of the prostate deepens the biological understanding of this lethal disease and provides a genetic basis for developing targeted therapies.

Pressure-Induced Free Exciton Emission in a Quasi-Zero-Dimensional Hybrid Lead Halide.

Structural dimensionality and electronic dimensionality play a crucial role in determining the type of excitonic emission in hybrid metal halides (HMHs). It is important but challenging to achieve free exciton (FE) emission in zero-dimensional (0D) HMHs based on the control over the electronic dimensionality. In this work, a quasi-0D HMH (C7 H15 N2 Br)2 PbBr4 with localized electronic dimensionality is prepared as a prototype model. With increasing pressure onto (C7 H15 N2 Br)2 PbBr4 , the broad and weak self-trapped exciton (STE) emission at ambient conditions is considerably enhanced before 3.6 GPa, which originates from more distorted [PbBr4 ]2- seesaw units upon compression. Notably, a narrow FE emission in (C7 H15 N2 Br)2 PbBr4 appears at 3.6 GPa, and then this FE emission is gradually strengthened up to 8.4 GPa. High pressure structural characterizations reveal that anisotropic contraction of (C7 H15 N2 Br)2 PbBr4 results in a noticeable reduction in the distance between adjacent [PbBr4 ]2- seesaw units, as well as an obvious enhancement of crystal stiffness. Consequently, the electronic connectivity in (C7 H15 N2 Br)2 PbBr4 is sufficiently promoted above 3.6 GPa, which is also supported with theoretical calculations. The elevation of electronic connectivity and enhanced stiffness together lead to pressure-induced FE emission and subsequent emission enhancement in quasi-0D (C7 H15 N2 Br)2 PbBr4 .

Crop diversification promotes soil aggregation and carbon accumulation in global agroecosystems: A meta-analysis.

Soil aggregation contributes to the stability of soil structure and the sequestration of soil organic carbon (SOC), making it an important indicator of soil health in agroecosystems. Crop diversification is considered a rational management practice for promoting sustainable agriculture. However, the complexity of cropping systems and crop species across different regions limits our comprehensive understanding of soil aggregation and associated carbon (C) content under crop diversification. Therefore, we conducted a meta-analysis by integrating 1924 observations from three diversification strategies (cover crops, crop rotation, and intercropping) in global agroecosystems to explore the effects of crop diversification on soil aggregates and associated C content. The results showed that compared to monoculture, crop diversification significantly increased the mean weight diameter and bulk soil C by 7.5% and 3.3%, respectively. Furthermore, there was a significant increase in the proportion of macroaggregates and their associated C content by 5.0% and 12.5%, while there was a significant decrease in the proportion of microaggregates as well as silt-clay fractions along with their associated C under crop diversification. Through further analysis, we identified several important factors that influence changes in soil aggregation and C content induced by crop diversification including climatic conditions, soil properties, crop species, and agronomic practices at the experimental sites. Interestingly, no significant differences were found among the three cropping systems (cover crops, crop rotation, and intercropping), while the effects induced by crop diversifications showed relatively consistent results for monoculture crops as well as additive crops and crop diversity. Moreover, the impact of crop diversification on soil aggregates and associated C content is influenced by soil properties such as pH and SOC. In general, our findings demonstrate that crop diversification promotes soil aggregation and enhances SOC levels in agroecosystems worldwide.

BioRTC model enables exploration of real time control strategies for stormwater biofilters.

Biofilters with real time control (RTC) have great potential to remove microbes from stormwater to protect human health for uses such as swimming and harvesting. However, RTC strategies need to be further explored and optimised for each specific location or end-use. This paper demonstrates that the newly developed BioRTC model can fulfil this requirement and allow effective and efficient exploration of the potential of RTC applications. We describe the development of BioRTC as the first RTC model for stormwater biofilters, including: selection of a 'base' model for microbial removal prediction, its modification to include RTC capabilities, as well as calibration and validation. BioRTC adequately predicted the performance of two previously developed RTC strategies, with Nash Sutcliffe Efficiency (Ec) ranging from 0.65 to 0.80. In addition, high parameter transferability was demonstrated during model validation, where we employed the parameter sets calibrated for another biofilter study without RTC to predict the performance of RTC biofilters. We then employed the BioRTC model to explore RTC applications on a hypothetical biofilter system located at the outlet of an existing catchment. With different scenarios, we tested the impact of input parameters such as RTC set-points and design characteristics, and evaluated the influence of operational conditions on the microbial removal performance of the hypothetical biofilter with RTC. The results showed that strategy rules, set-point values, and biofilter design all govern the performance of RTC biofilters, and that operational conditions could impact the suitability of different RTC strategies. Particularly, the presence of Pareto fronts established that muti-objective optimisation is necessary to balance competing needs. These results underscore the importance of RTC, which allows for local experimentation, climate change adaptation, and adjustment to changing demands for the harvested water. Furthermore, they illustrate the practical use of the newly developed BioRTC model, enabling researchers and practitioners to explore and assess potential RTC strategies and scenarios quickly and cost-effectively.

Development and validation of a nomogram for predicting in-hospital mortality in patients with nonhip femoral fractures.

BACKGROUND: The incidence of nonhip femoral fractures is gradually increasing, but few studies have explored the risk factors for in-hospital death in patients with nonhip femoral fractures in the ICU or developed mortality prediction models. Therefore, we chose to study this specific patient group, hoping to help clinicians improve the prognosis of patients. METHODS: This is a retrospective study based on the data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Least absolute shrinkage and selection operator (LASSO) regression was used to screen risk factors. The receiver operating characteristic (ROC) curve was drawn, and the areas under the curve (AUC), net reclassification index (NRI) and integrated discrimination improvement (IDI) were calculated to evaluate the discrimination of the model. The consistency between the actual probability and the predicted probability was assessed by the calibration curve and Hosmer-Lemeshow goodness of fit test (HL test). Decision curve analysis (DCA) was performed, and the nomogram was compared with the scoring system commonly used in clinical practice to evaluate the clinical net benefit. RESULTS: The LASSO regression analysis showed that heart rate, temperature, red blood cell distribution width, blood urea nitrogen, Glasgow Coma Scale (GCS), Simplified Acute Physiology Score II (SAPSII), Charlson comorbidity index and cerebrovascular disease were independent risk factors for in-hospital death in patients with nonhip femoral fractures. The AUC, IDI and NRI of our model in the training set and validation set were better than those of the GCS and SAPSII scoring systems. The calibration curve and HL test results showed that our model prediction results were in good agreement with the actual results (P = 0.833 for the HL test of the training set and P = 0.767 for the HL test of the validation set). DCA showed that our model had a better clinical net benefit than the GCS and SAPSII scoring systems. CONCLUSION: In this study, the independent risk factors for in-hospital death in patients with nonhip femoral fractures were determined, and a prediction model was constructed. The results of this study may help to improve the clinical prognosis of patients with nonhip femoral fractures.

Experimental Study on the Determinant Factors and Energy Criterion of Coal and Gas Outbursts.

A series of coal and gas outburst tests were conducted on coal seams in north China to determine the important order of gas pressure, in situ stress, and coal strength during coal and gas outbursts. And the typical phenomena of coal and gas outbursts were investigated. In addition, improved outburst energy equations were built to study the coal energy evolution process during coal and gas outbursts. The results show that the coal strength has the strongest influence on coal and gas outbursts, followed by the gas pressure and the in situ stress. The weights of pulverized coal with a particle size of less than 0.28 mm are consistent with the changing trend of the total weights of the pulverized coal particles in the corresponding outburst interval. Furthermore, the results suggest that the gas pressure monitored by the sensors close to the outburst hole begins to drop first and lasts for the longest time. The outburst coal presents obvious fracture and pulverization damage characteristics, and the pulverization damage features of the coal near the outburst hole are more obvious. In addition, the improved outburst energy equation was established, and the rationality of the improved outburst energy equation was verified by using the outburst orthogonal simulation experimental data and the on-site outburst accident cases. The results of this experiment have important guiding significance for preventing and controlling the occurrence of coal and gas outbursts and ensuring safe and efficient mining of coal mines.

Metagenomics reveals the abundance and accumulation trend of antibiotic resistance gene profile under long-term no tillage in a rainfed agroecosystem.

Widespread soil resistance can seriously endanger sustainable food production and soil health. Conservation tillage is a promising practice for improving soil structure and health. However, the impact of long-term no-tillage on the presence of antibiotic resistance genes in agricultural soils remains unexplored. Based on the long-term (>11 yr) tillage experimental fields that include both conservation tillage practices [no tillage (ZT)] and conventional tillage practices [plough tillage (PT)], we investigated the accumulation trend of antibiotic resistance genes (ARGs) in farmland soils under long-term no-tillage conditions. We aimed to provide a scientific basis for formulating agricultural production strategies to promote ecological environment safety and human health. In comparison to PT, ZT led to a considerable reduction in the relative abundance of both antibiotic resistance genes and antibiotic target gene families in the soil. Furthermore, the abundance of all ARGs were considerably lower in the ZT soil. The classification of drug resistance showed that ZT substantially decreased the relative abundance of Ethambutol (59.97%), ß-lactams (44.87%), Fosfomycin (35.82%), Sulfonamides (34.64%), Polymyxins (33.67%), MLSB (32.78%), Chloramphenicol (28.57%), Multi-drug resistance (26.22%), Efflux pump (23.46%), Aminoglycosides (16.79%), Trimethoprim (13.21%), Isoniazid (11.34%), Fluoroquinolone (6.21%) resistance genes, compared to PT soil. In addition, the abundance of the bacterial phyla Proteobacteria, Actinobacteria, Acidobacteria, and Gemmatimonadetes decreased considerably. The Mantel test indicated that long-term ZT practices substantially increased the abundance of beneficial microbial flora and inhibited the enrichment of ARGs in soil by improving soil microbial diversity, metabolic activity, increasing SOC, TN, and available Zn, and decreasing pH. Overall, long-term no-tillage practices inhibit the accumulation of antibiotic resistance genes in farmland soil, which is a promising agricultural management measure to reduce the accumulation risk of soil ARGs.

Retraction to the prognostic value of the pretreatment lung immune prognostic index in patients with metastatic hormone-sensitive and castration-resistant prostate cancer.

[This retracts the article DOI: 10.21037/atm-22-4318.].

Preparation and Validation of a Longitudinally and Transversely Stiffened Panel Based on Hybrid RTM Composite Materials.

In the face of the difficulty in achieving high-quality integrated molding of longitudinally and transversely stiffened panels for helicopters by resin-matrix composite materials, we combine the prepreg process and the resin transfer molding (RTM) process to propose a hybrid resin transfer molding (HRTM) for composite stiffened panel structures. The HRTM process uses a mixture of prepreg and dry fabric to lay up a hybrid fiber preform, and involves injecting liquid resin technology. Using this process, a longitudinally and transversely stiffened panel structure is prepared, and the failure modes under compressive load are explored. The results show that at the injection temperature of the RTM resin, the prepreg resin dissolves slightly and has little effect on the viscosity of the RTM resin. Both resins have good miscibility at the curing temperature, which allows for the overall curing of the resin. A removable box core mold for the HRTM molding is designed, which makes it convenient for the mold to be removed after molding and is suitable for the overall molding of the composite stiffened panel. Ultrasonic C-scan results show that the internal quality of the composite laminates prepared using the HRTM process is good. A compression test proves that the composite stiffened panel undergoes sequential buckling deformation in different areas under compressive load, followed by localized debonding and delamination of the skin, and finally failure due to the fracture of the longitudinal reinforcement ribs on both sides. The compressive performance of the test specimen is in good agreement with the finite element simulation results. The verification results show that the HRTM process can achieve high-quality integrated molding of the composite longitudinally and transversely stiffened panel structure.

Mutations in epigenetic regulator KMT2C detected by liquid biopsy are associated with worse survival in prostate cancer patients.

Background: KMT2 (lysine methyltransferase) family enzymes are epigenetic regulators that activate gene transcription. KMT2C is mainly involved in enhancer-associated H3K4me1, and is also one of the top mutated genes in cancer (6.6% in pan-cancer). Currently, the clinical significance of KMT2C mutations in prostate cancer is understudied. Methods: We included 221 prostate cancer patients diagnosed between 2014 and 2021 in West China Hospital of Sichuan University with cell-free DNA-based liquid biopsy test results in this study. We investigated the association between KMT2C mutations, other mutations, and pathways. Furthermore, we evaluated the prognostic value of KMT2C mutations, measured by overall survival (OS) and castration resistance-free survival (CRFS). Also, we explored the prognostic value of KMT2C mutations in different patient subgroups. Lastly, we investigated the predictive value of KMT2C mutations in individuals receiving conventional combined anti-androgen blockade (CAB) and abiraterone (ABI) as measured by PSA progression-free survival (PSA-PFS). Results: The KMT2C mutation rate in this cohort is 7.24% (16/221). KMT2C-mutated patients showed worse survival than KMT2C-wild type (WT) patients regarding both CRFS and OS (CRFS: mutated: 9.9 vs. WT: 22.0 months, p = 0.015; OS: mutated: 71.9 vs. WT 137.4 months, p = 0.012). KMT2C mutations were also an independent risk factor in OS [hazard ratio: 3.815 (1.461, 9.96), p = 0.006] in multivariate analyses. Additionally, we explored the association of KMT2C mutations with other genes. This showed that KMT2C mutations were associated with Serine/Threonine-Protein Kinase 11 (STK11, p = 0.004) and Catenin Beta 1 (CTNNB1, p = 0.008) mutations. In the CAB treatment, KMT2C-mutated patients had a significantly shorter PSA-PFS compared to KMT2C-WT patients. (PSA-PFS: mutated: 9.9 vs. WT: 17.6 months, p = 0.014). Moreover, KMT2C mutations could effectively predict shorter PSA-PFS in 10 out of 23 subgroups and exhibited a strong trend in the remaining subgroups. Conclusions: KMT2C-mutated patients showed worse survival compared to KMT2C-WT patients in terms of both CRFS and OS, and KMT2C mutations were associated with STK11 and CTNNB1 mutations. Furthermore, KMT2C mutations indicated rapid progression during CAB therapy and could serve as a potential biomarker to predict therapeutic response in prostate cancer.

Genomic and transcriptomic features between primary and paired metastatic fumarate hydratase-deficient renal cell carcinoma.

BACKGROUND: Fumarate hydratase-deficient renal cell carcinoma (FH-RCC) is a rare highly aggressive subtype of kidney cancer for which the distinct genomic, transcriptomic, and evolutionary relationships between metastatic and primary lesions are still unclear. METHODS: In this study, whole-exome, RNA-seq, and DNA methylation sequencing were performed on primary-metastatic paired specimens from 19 FH-RCC cases, including 23 primary and 35 matched metastatic lesions. Phylogenetic and clonal evolutionary analyses were used to investigate the evolutionary characteristics of FH-RCC. Transcriptomic analyses, immunohistochemistry, and multiple immunofluorescence experiments were performed to identify the tumor microenvironmental features of metastatic lesions. RESULTS: Paired primary and metastatic lesions generally showed similar characteristics of tumor mutation burden, tumor neoantigen burden, microsatellite instability score, CNV burden, and genome instability index. Notably, we identified an FH-mutated founding MRCA (the most recent common ancestor) clone that dominated the early evolutionary trajectories in FH-RCC. Although both primary and metastatic lesions manifested high immunogenicity, metastatic lesions exhibited higher enrichment of T effector cells and immune-related chemokines, together with upregulation of PD-L1, TIGIT, and BTLA. In addition, we found that concurrent NF2 mutation may be associated with bone metastasis and upregulation of cell cycle signature in metastatic lesions. Furthermore, although in FH-RCC metastatic lesions in general shared similar CpG island methylator phenotype with primary lesions, we found metastatic lesions displaying hypomethylated chemokine and immune checkpoints related genomic loci. CONCLUSIONS: Overall, our study demonstrated the genomic, epigenomic, and transcriptomic features of metastatic lesions in FH-RCC and revealed their early evolutionary trajectory. These results provided multi-omics evidence portraying the progression of FH-RCC.

Primary renal mucinous adenocarcinoma masquerading as a giant renal cyst: a case report.

Mucinous adenocarcinoma of the kidney is rarely reported in the literature. We present a previously unreported mucinous adenocarcinoma arising from the renal parenchyma. A 55-year-old male patient with no complaints showed a large cystic hypodense lesion in the upper left kidney on contrast-enhanced computed tomography (CT) scan. A left renal cyst was initially considered, and a partial nephrectomy (PN) was performed. During the operation, a large amount of jelly-like mucus and bean-curd-like necrotic tissue was found in the focus. The pathological diagnosis was mucinous adenocarcinoma, and further systemic examination revealed no clinical evidence of primary disease elsewhere. Then the patient underwent left radical nephrectomy (RN), and the cystic lesion was found in the renal parenchyma, while neither the collecting system nor the ureters were involved. Postoperative sequential chemotherapy and radiotherapy were administered, and no signs of disease recurrence were observed over 30 months of follow-up. Based on a literature review, we summarize the lesion with rarity and the associated dilemma in preoperative diagnosis and treatment. Given the high degree of malignancy, a careful history analysis accompanied by dynamic observation of imaging and tumor markers is recommended for the diagnosis of the disease. Comprehensive treatment based on surgery may improve its clinical outcomes.