A Study of the Effects of Moisture on Composite-to-Metal Double-Lap Shear Joints.

This work investigated the effects of moisture absorption treatment on composite-to-metal double-lap shear joints (DLSJs) bonded with epoxy adhesive film through experiments and simulations. The composite-to-metal DLSJ can be divided into five parts (the interface between the composite and adhesive, the interface between the adhesive and metal, the composite adherend, the metal adherend, and the adhesive layer). First, the wet-dependent properties of the adhesive and interfaces were obtained through adhesive tensile tests and GC tests, which showed that the properties of the adhesive and interfaces were significantly affected by the moist environment. Then, tensile tests of the composite-to-metal double-lap shear joints were carried out in dry and wet environments. Finally, based on the experimental investigations, a finite element (FE) model that considered cohesive damage was established for simulating damage evolution and predicting the failure loads and failure modes of the DLSJs. The results of both the experimental and numerical tests show that the DLSJ failure load decreases significantly after immersion in 95 °C water, and the major failure mode transfers from adhesive failure to interface failure. The research results provide a theoretical basis or basic data for the structural design of adhesively bonded composite-to-metal.

Development and validation of a novel nomogram to avoid unnecessary biopsy in patients with PI-RADS category ≥ 4 lesions and PSA ≤ 20 ng/ml.

OBJECTIVES: To develop and validate a prediction model for identifying non-prostate cancer (non-PCa) in biopsy-naive patients with PI-RADS category ≥ 4 lesions and PSA ≤ 20 ng/ml to avoid unnecessary biopsy. PATIENTS AND METHODS: Eligible patients who underwent transperineal biopsies at West China Hospital between 2018 and 2022 were included. The patients were randomly divided into training cohort (70%) and validation cohort (30%). Logistic regression was used to screen for independent predictors of non-PCa, and a nomogram was constructed based on the regression coefficients. The discrimination and calibration were assessed by the C-index and calibration plots, respectively. Decision curve analysis (DCA) and clinical impact curves (CIC) were applied to measure the clinical net benefit. RESULTS: A total of 1580 patients were included, with 634 non-PCa. Age, prostate volume, prostate-specific antigen density (PSAD), apparent diffusion coefficient (ADC) and lesion zone were independent predictors incorporated into the optimal prediction model, and a corresponding nomogram was constructed ( https://nomogramscu.shinyapps.io/PI-RADS-4-5/ ). The model achieved a C-index of 0.931 (95% CI, 0.910-0.953) in the validation cohort. The DCA and CIC demonstrated an increased net benefit over a wide range of threshold probabilities. At biopsy-free thresholds of 60%, 70%, and 80%, the nomogram was able to avoid 74.0%, 65.8%, and 55.6% of unnecessary biopsies against 9.0%, 5.0%, and 3.6% of missed PCa (or 35.9%, 30.2% and 25.1% of foregone biopsies, respectively). CONCLUSION: The developed nomogram has favorable predictive capability and clinical utility can help identify non-PCa to support clinical decision-making and reduce unnecessary prostate biopsies.

Epigenetic modification of PHLDA2 is associated with tumor microenvironment and unfavorable outcome of immune checkpoint inhibitor-based therapies in clear cell renal cell carcinoma.

BACKGROUND: A substantial proportion of patients with metastatic clear cell renal cell carcinoma (ccRCC) cannot derive benefit from immune checkpoint inhibitor (ICI) plus anti-angiogenic agent combination therapy, making identification of predictive biomarkers an urgent need. The members of pleckstrin homology-like domain family A (PHLDA) play critical roles in multiple cancers, whereas their roles in ccRCC remain unknown. METHODS: Transcriptomic, clinical, genetic alteration and DNA methylation data were obtained for integrated analyses from TCGA database. RNA sequencing was performed on 117 primary tumors and 79 normal kidney tissues from our center. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis, gene set enrichment analysis were performed to explore transcriptomic features. Data from three randomized controlled trials (RCT), including CheckMate025, IMmotion151, JAVELIN101, were obtained for validation. RESULTS: Members of PHLDA family were dysregulated in pan-cancer. Elevated PHLDA2 expression was associated with adverse clinicopathologic parameters and worse prognosis in ccRCC. Aberrant DNA hypomethylation contributed to up-regulation of PHLDA2. An immunosuppressive microenvironment featured by high infiltrates of Tregs and cancer-associated fibroblasts, was observed in ccRCC with higher PHLDA2 expression. Utilizing data from three RCTs, the association of elevated PHLDA2 expression with poor therapeutic efficacy of ICI plus anti-angiogenic combination therapy was confirmed. CONCLUSIONS: Our study revealed that elevated PHLDA2 expression regulated by DNA hypomethylation was correlated with poor prognosis and immunosuppressive microenvironment, and highlighted the role of PHLDA2 as a robust biomarker for predicting therapeutic efficacy of ICI plus anti-angiogenic agent combination therapy in ccRCC, which expand the dimension of precision medicine.

Grafting Carbon Fibers with Graphene via a One-Pot Aryl Diazonium Reaction to Refine the Interface Performance of T1100-Grade CF/BMI Composites.

In this study, a one-pot aryl diazonium reaction was used as a simple and mild method to graft graphene onto the smooth and inert surface of T1100-grade carbon fiber (CF) through covalent bonding without any damage on CF, to refine the interface performance of CF/bismaleimide (BMI) composites. XPS, SEM, AFM, and dynamic contact angle testing (DCAT) were used to characterize chemical activity, morphologies, and wettability on untreated and grafted CF surfaces. Meanwhile, the impact of the graft method on the tensile strength of CF was also examined using the monofilament tensile test. IFSS between CF grafted with graphene and BMI resin achieved 104.2 MPa after modification, increasing from 85.5 MPa by 21.8%, while the tensile strength did not decrease compared to the pristine CF. The mechanism of this interface enhancement might be better chemical bonding and mechanical interlock between CF grafted with graphene and BMI resin, which is generated from the high surface chemical activity and rough structure of graphene. This study may propose a simple and mild method to functionalize the CF surface and enhance the interface performance of composites without compromising the tensile properties of T1100-grade CF.

Patients with ASPSCR1-TFE3 fusion achieve better response to ICI based combination therapy among TFE3-rearranged renal cell carcinoma.

BACKGROUND: TFE3-rearranged renal cell carcinoma (TFE3-rRCC) is a rare but highly heterogeneous renal cell carcinoma (RCC) entity, of which the clinical treatment landscape is largely undefined. This study aims to evaluate and compare the efficacy of different systemic treatments and further explore the molecular correlates. METHODS: Thirty-eight patients with metastatic TFE3-rRCC were enrolled. Main outcomes included progression-free survival (PFS), overall survival, objective response rate (ORR) and disease control rate. RNA sequencing was performed on 32 tumors. RESULTS: Patients receiving first-line immune checkpoint inhibitor (ICI) based combination therapy achieved longer PFS than those treated without ICI (median PFS: 11.5 vs. 5.1 months, P = 0.098). After stratification of fusion partners, the superior efficacy of first-line ICI based combination therapy was predominantly observed in ASPSCR1-TFE3 rRCC (median PFS: not reached vs. 6.5 months, P = 0.01; ORR: 67.5% vs. 10.0%, P = 0.019), but almost not in non-ASPSCR1-TFE3 rRCC. Transcriptomic data revealed enrichment of ECM and collagen-related signaling in ASPSCR1-TFE3 rRCC, which might interfere with the potential efficacy of anti-angiogenic monotherapy. Whereas angiogenesis and immune activities were exclusively enriched in ASPSCR1-TFE3 rRCC and promised the better clinical outcomes with ICI plus tyrosine kinase inhibitor combination therapy. CONCLUSIONS: The current study represents the largest cohort comparing treatment outcomes and investigating molecular correlates of metastatic TFE3-rRCC based on fusion partner stratification. ICI based combination therapy could serve as an effective first-line treatment option for metastatic ASPSCR1-TFE3 rRCC patients. Regarding with other fusion subtypes, further investigations should be performed to explore the molecular mechanisms to propose pointed therapeutic strategy accordingly.

The incidence of immune-related adverse events (irAEs) and their association with clinical outcomes in advanced renal cell carcinoma and urothelial carcinoma patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis.

BACKGROUND: This study aimed to summarize the occurrence of immune-related adverse events (irAEs) and further evaluate their association with clinical outcomes in patients with advanced renal cell carcinoma (RCC) and urothelial carcinoma (UC) treated with immune checkpoint inhibitors (ICIs). METHODS: A comprehensive search of PubMed, Embase, and the Cochrane Library up to December 2023 was conducted to identify eligible studies. The details of irAEs and data regarding their correlation with clinical outcomes were extracted. R software was used for meta-analysis. RESULTS: A total of 27 studies involving 6148 patients with RCC or UC were included. The pooled overall incidence for any-grade and grade ≥ 3 irAEs was 44.2 % (95 % CI: 38.1 %-50.5 %) and 15.7 % (95 % CI: 11.4 %-21.1 %), respectively. Compared to those without any irAEs, patients with irAEs showed improved PFS (HR = 0.44, 95 % CI: 0.35-0.56, p < 0.01) and OS (HR = 0.47, 95 % CI: 0.42-0.51, p < 0.01), as well as higher ORR (OR = 3.59, 95 % CI: 3.01-4.29, p < 0.01) and DCR (OR = 4.23, 95 % CI: 3.06-5.84, p < 0.01). Subgroup analysis indicated that clinical outcome improvements were associated with the occurrence of irAEs, regardless of tumor type or ICI agent. Notably, patients with cutaneous irAEs, thyroid dysfunction, and grade ≤ 2 irAEs had a higher probability to achieve better survival benefits from ICI-based therapy, while pulmonary irAEs and grade ≥ 3 irAEs seemed to have a negative impact on OS. Additionally, systemic glucocorticoids administration did not affect survival outcomes. CONCLUSION: Our findings suggest that the occurrence of irAEs could be considered as a potential prognostic factor for predicting the efficacy of ICIs in patients with advanced RCC and UC.

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.

Effective oxidation and adsorption of As(III) in water by nanoconfined Ce-Mn binary oxides with excellent reusability.

Herein, a highly efficient As(III) purifier Ce-Mn@N201 with excellent reusability was developed by stepwise precipitating hydrated cerium(IV) oxides (HCO) and hydrated manganese(IV) oxides (HMO) inside N201, a widely-used gel-type anion exchange resin. Owing to confinement of unique nanopores in N201, the in-situ generated nanoparticles (NPs) inside Ce-Mn@N201 were highly dispersed with ultra-small sizes of around 2.6 nm. Results demonstrated that HMO NPs effectively oxidized As(III) to As(V) with the conversion of Mn(IV) to Mn(II), while the generated Mn2+ was mostly re-adsorbed onto the negatively-charged surface of HMO NPs. During the regeneration process by simple alkaline treatment, the re-adsorbed Mn2+ was firstly precipitated as (hydr)oxides of Mn(II) and then oxidized to HMO NPs by dissolved oxygen to fully refresh its oxidation capacity. Though HCO NPs mainly served as adsorbent for arsenic, they could partially oxidize As(III) to As(V) at the beginning, while the oxidation capacities continuously diminished with the irreversible conversion of Ce(IV) to Ce(III). In 10 consecutive adsorption-regeneration cycle, Ce-Mn@N201 efficiently decontaminated As(III) from 500 µg/L to below 5 µg/L with Mn2+ leaching less than 0.3% per batch. During 3 cyclic fixed-bed adsorptions, Ce-Mn@N201 steadily produced 8500-9150 bed volume (BV) and 3150-3350 BV drinkable water from the synthesized and real groundwater, respectively, with Mn leaching in effluent constantly < 100 µg/L.

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 noninvasive 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 16 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.

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.

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 patients with metastasis. 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.

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 .

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.

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.