A community challenge to predict clinical outcomes after immune checkpoint blockade in non-small cell lung cancer.

BACKGROUND: Predictive biomarkers of immune checkpoint inhibitor (ICI) efficacy are currently lacking for non-small cell lung cancer (NSCLC). Here, we describe the results from the Anti-PD-1 Response Prediction DREAM Challenge, a crowdsourced initiative that enabled the assessment of predictive models by using data from two randomized controlled clinical trials (RCTs) of ICIs in first-line metastatic NSCLC. METHODS: Participants developed and trained models using public resources. These were evaluated with data from the CheckMate 026 trial (NCT02041533), according to the model-to-data paradigm to maintain patient confidentiality. The generalizability of the models with the best predictive performance was assessed using data from the CheckMate 227 trial (NCT02477826). Both trials were phase III RCTs with a chemotherapy control arm, which supported the differentiation between predictive and prognostic models. Isolated model containers were evaluated using a bespoke strategy that considered the challenges of handling transcriptome data from clinical trials. RESULTS: A total of 59 teams participated, with 417 models submitted. Multiple predictive models, as opposed to a prognostic model, were generated for predicting overall survival, progression-free survival, and progressive disease status with ICIs. Variables within the models submitted by participants included tumor mutational burden (TMB), programmed death ligand 1 (PD-L1) expression, and gene-expression-based signatures. The best-performing models showed improved predictive power over reference variables, including TMB or PD-L1. CONCLUSIONS: This DREAM Challenge is the first successful attempt to use protected phase III clinical data for a crowdsourced effort towards generating predictive models for ICI clinical outcomes and could serve as a blueprint for similar efforts in other tumor types and disease states, setting a benchmark for future studies aiming to identify biomarkers predictive of ICI efficacy. TRIAL REGISTRATION: CheckMate 026; NCT02041533, registered January 22, 2014. CheckMate 227; NCT02477826, registered June 23, 2015.

Detection and elimination of trace d-lactic acid in lignocellulose biorefining chain: Generation, flow, and impact on chiral lactide synthesis.

High chiral purity of lactic acid is a crucial indicator for the synthesis of chiral lactide as the primary intermediate chemical for ring-open polymerization of high molecular weight polylactic acid (PLA). Lignocellulose biomass is the most promising carbohydrate feedstock for commercial production of PLA, but the presence of trace d-lactic acid in the biorefinery chain adversely affects the synthesis and quality of chiral lactide. This study analyzed the fingerprint of trace  d-lactic acid in the biorefinery chain and found that the major source of  d-lactic acid comes from lignocellulose feedstock. The naturally occurring lactic acid bacteria and water-soluble carbohydrates in lignocellulose feedstock provide the necessary conditions for  d-lactic acid generation. Three strategies were proposed to eliminate the generation pathway of  d-lactic acid, including reduction of moisture content, conversion of water-soluble carbohydrates to furan aldehydes in pretreatment, and conversion to  l-lactic acid by inoculating engineered  l-lactic acid bacteria. The natural reduction of lactic acid content in lignocellulose feedstock during storage was observed due to the lactate oxidase-catalyzed oxidation of  l- and  d-lactic acids. This study provided an important support for the production of cellulosic  l-lactic acid with high chiral purity.

Intricate microbe-plant-metabolic remodeling mediated by intercropping enhances the quality of Panax quinquefolius L.

Improving the cultivation mode and technology for traditional Chinese medicine has become important for its sustainable development. Monoculture enhances plant diseases, which decreases yield and quality. Intercropping is an effective measure to counterbalance that negative effect. In this study, we focused on Panax quinquefolium L. (ginseng) and four treatments were set up: the control without intercropping, P. quinquefolius + ryegrass (Lolium perenne L.), P. quinquefolius + red clover (Trifolium pratense L.), and P. quinquefolius + ryegrass + red clover. An LC-MS/MS system was used to detect the changes in the P. quinquefolius secondary metabolites, and high-throughput sequencing technology was used to determine the changes in the P. quinquefolius' rhizosphere soil microorganisms. Ginsenoside content, soil enzyme activities, and arbuscular mycorrhizal infection rate of P. quinquefolius were also measured using HPLC, ELISA kits, and microscopy, respectively. Co-intertia and Pearson's analysis were performed to explore the relationship between the metabolites and the P. quinquefolius microorganisms. Intercropping significantly increased the content of ginsenoside metabolites and recruited a large number of beneficial bacteria to the P. quinquefolius rhizosphere. The P. quinquefolius secondary metabolites were associated with the rhizosphere microbial community. For example, the dominant microorganisms, such as Acidobacteriota and Chloroflexi, played a key role in promoting the synthesis of ginsenoside Rd and (20R) ginsenoside Rg3 by P. quinquefolius. Intercropping led to changes in the P. quinquefolius secondary metabolites by driving and reshaping the rhizosphere microorganisms. These findings revealed the potential application of intercropping for improving the quality of P. quinquefolius.

Silver peroxide-incorporated carbon dots with high photothermal performance for combating bacteria.

The widespread use of antibiotics often increases bacterial resistance. Herein, we reported a silver peroxide-incorporated carbon dots (defined as Ag2O2-CDs) with high photothermal conversion efficiency viain situoxidation process. The prepared Ag2O2-CDs exhibited ultra-small size of 2.0 nm and hybrid phase structure. Meanwhile, the Ag2O2-CDs were of a similar optical performance comparing with traditional carbon dots (CDs). Importantly, the incorporation of Ag2O2into CDs significantly enhanced photothermal conversion efficiency from 3.8% to 28.5%. By combining silver ion toxicity and photothermal ablation, the Ag2O2-CDs were capable of destroying gram-positive and gram-negative bacterium effectively. These findings demonstrated that the Ag2O2-CDs could be served as a potential antibacterial agent for clinical applications.

Minimum-Energy Conical Intersections by Compressed Multistate Pair-Density Functional Theory.

Compressed multistate pair-density functional theory (CMS-PDFT) is a multistate version of multiconfiguration pair-density functional theory that can capture the correct topology of coupled potential energy surfaces (PESs) around conical intersections. In this work, we develop interstate coupling vectors (ISCs) for CMS-PDFT in the OpenMolcas and PySCF/mrh electronic structure packages. Yet, the main focus of this work is using ISCs to calculate minimum-energy conical intersections (MECIs) by CMS-PDFT. This is performed using the projected constrained optimization method in OpenMolcas, which uses ISCs to restrain the iterations to the conical intersection seam. We optimize the S1/S0 MECIs for ethylene, butadiene, and benzene and show that CMS-PDFT gives smooth PESs in the vicinities of the MECIs. Furthermore, the CMS-PDFT MECIs are in good agreement with the MECI calculated by the more expensive XMS-CASPT2 method.

Azaphilone pigments from the marine-derived Penicillium sclerotium UJNMF 0503 and their neuroprotective potential against H2O2-induced cell apoptosis through modulating PI3K/Akt pathway.

Azaphilones represent a particular group of fascinating pigments from fungal source, with easier industrialization and lower cost than the traditional plant-derived pigments, and they also display a wide range of pharmacological activities. Herein, 28 azaphilone analogs, including 12 new ones, were obtained from the fermentation culture of a marine fungus Penicillium sclerotium UJNMF 0503. Their structures were elucidated by MS, NMR and ECD analyses, together with NMR and ECD calculations and biogenetic considerations. Among them, compounds 1 and 2 feature an unusual natural benzo[d][1,3]dioxepine ring embedded with an orthoformate unit, while 3 and 4 represent the first azaphilone examples incorporating a novel rearranged 5/6 bicyclic core and a tetrahydropyran ring on the side chain, respectively. Our bioassays revealed that half of the isolates exhibited neuroprotective potential against H2O2-induced injury on RSC96 cells, while compound 13 displayed the best rescuing capacity toward the cell viability by blocking cellular apoptosis, which was likely achieved by upregulating the PI3K/Akt signaling pathway.

Utilizing a modified-Postoperative Morbidity Survey for assessing morbidity after laparoscopic or robot-assisted radical prostatectomy: a retrospective observational study.

BACKGROUND: Compared with open radical prostatectomy (RP), laparoscopic or robot-assisted RP have shown a notable decrease in the incidence of organ dysfunction or potentially life-threating complications after surgery. However, despite advances, the postoperative length of hospital stay (LOS) remains longer than desired in many cases. The Postoperative Morbidity Survey (POMS) is a simple approach to detect complications capable of prolonging LOS. The primary objective of this study was to outline the incidence and type of early morbidity following laparoscopic or robot-assisted RP using modified POMS(m-POMS). The secondary objective was to investigate the correlation between m-POMS and postoperative LOS. METHODS: A retrospective study of the electronic health records was performed for all eligible patients undergoing laparoscopic or robot-assisted RP over a one-year period (August 1, 2022 to July 31, 2023). Morbidity as defined by m-POMS was collected on postoperative day 1 (POD1), POD3, POD5 and POD8. Poisson regression models were employed to assess the correlation between positive m-POMS and postoperative LOS. RESULTS: A total of 121 patients were included. Morbidity, as measured by m-POMS, occurred on POD1 (19.01%, 95% CI [13.01%, 26.91%]), POD3 (18.81%, 95% CI [12.39%, 27.52%]), POD5 (30.23%, 95% CI [18.60%, 45.10%]) and POD8 (35.29%, 95% CI [17.31%, 58.70%]). Two prevalent domains with positive m-POMS scores were infectious and pulmonary. The occurrence of morbidity as indicated by m-POMS was correlated with longer median (IQR) postoperative LOS on POD1 7 (5, 9) versus 4 (4, 6), POD3 7 (6, 11) versus 5(4, 6), and POD5 11 (6.5, 11) versus 7(6, 9) (p < 0.05) compared with patients who did not encounter m-POMS-assessed morbidity. Regression analysis showed that m-POMS-defined morbidity was correlated with longer postoperative LOS on POD1 and POD3. CONCLUSIONS: The incidence of early morbidity, as defined by m-POMS following radical prostatectomy, was approximately 20%, with infectious and pulmonary complications being the most prevalent. Short-term morbidity assessed by m-POMS was significantly associated with prolonged LOS.

First report of Metschnikowia bicuspidata infection in the oriental river prawn (Macrobrachium nipponense, de Haan) in China.

During breeding, some oriental river prawns (Macrobrachium nipponense, de Haan), an important aquaculture species in China, exhibit yellowish-brown body colouration, reduced appetite, and vitality. Diseased prawns revealed characteristic emulsifying disease signs, including whitened musculature, hepatopancreatic tissues, milky haemolymph, and non-coagulation. The present study investigated the causative agent of M. nipponense infection through isolation, histopathology, molecular sequencing, and infection experiments. The pathogenic strain exhibited distinctive white colonies on Bengal red medium, with microscopic examination confirming the presence of yeast cells. Histopathological analysis revealed prominent pathological alterations and yeast cell infiltration in muscles, hepatopancreas and gills. Additionally, 26S rDNA sequencing of the isolated yeast strain LNMN2022 revealed Metschnikowia bicuspidata (GenBank: OR518659) as the causative agent. This strain exhibited a 98.28% sequence homology with M. bicuspidata LNMB2021 (GenBank: OK094821) and 96.62% with M. bicuspidata LNES0119 (GenBank: OK073903). The pathogenicity test confirmed that M. bicuspidata elicited clinical signs in M. nipponense consistent with those observed in natural populations, and the median lethal concentration was determined to be 3.3 × 105 cfu/mL. This study establishes a foundation for further investigations into the host range and epidemiological characteristics of the pathogen M. bicuspidata in aquatic animals and provides an empirical basis for disease management in M. nipponense.

Linc01588 deletion inhibits the malignant biological characteristics of hydroquinone-induced leukemic cells via miR-9-5p/SIRT1.

Leukemia caused by environmental chemical pollutants has attracted great attention, the malignant leukemic transformation model of TK6 cells induced by hydroquinone (HQ) has been previously found in our team. However, the type of leukemia corresponding to this malignant transformed cell line model needs further study and interpretation. Furthermore, the molecular mechanism of malignant proliferation of leukemic cells induced by HQ remains unclear. This study is the first to reveal the expression of aberrant genes in leukemic cells of HQ-induced malignant transformation, which may correspond to chronic lymphocytic leukemia (CLL). The expression of Linc01588, a long non-coding RNA (lncRNA), was significantly up-regulated in CLL patients and leukemic cell line model which previously described. After gain-of-function assays and loss-of-function assays, feeble cell viability, severe apoptotic phenotype and the increased secretion of TNF-α were easily observed in malignant leukemic TK6 cells with Linc01588 deletion after HQ intervention. The tumors derived from malignant TK6 cells with Linc01588 deletion inoculated subcutaneously in nude mice were smaller than controls. In CLL and its cell line model, the expression of Linc01588 and miR-9-5p, miR-9-5p and SIRT1 were negative correlation respectively in CLL and cell line model, while the expression of Linc01588 and SIRT1 were positive correlation. The dual-luciferase reporter assay showed that Linc01588 & miR-9-5p, miR-9-5p & SIRT1 could bind directly, respectively. Furthermore, knockdown of miR-9-5p successfully rescued the severe apoptotic phenotype and the increased secretion of TNF-α caused by the Linc01588 deletion, the deletion of Linc01588 in human CLL cell line MEC-2 could also inhibit malignant biological characteristics, and the phenotype caused by the deletion of Linc01588 could also be rescued after overexpression of SIRT1. Moreover, the regulation of SIRT1 expression in HQ19 cells by Linc01588 and miR-9-5 P may be related to the Akt/NF-κB pathway. In brief, Linc01588 deletion inhibits the malignant biological characteristics of HQ-induced leukemic cells via miR-9-5p/SIRT1, and it is a novel and hopeful clue for the clinical targeted therapy of CLL.

Grifolin Induces Cell Death of Human Lung Cancer A549 Cell Line via Inhibiting KRAS-Mediated Multiple Signaling Pathways.

In the current work, grifolin was obtained from the twigs and leaves of Daphne genkwa for the first time and displayed significant growth inhibition against human lung carcinoma A549 cells. Subsequent in vitro antitumor evaluation revealed that grifolin could induce remarkable cell apoptosis and G0/G1 phase arrest, as well as block cell migration and invasion. In addition, grifolin also disrupted cellular energy metabolism by inducing reactive oxygen species, reducing adenosine triphosphate and mitochondrial membrane potential, and damaging DNA synthesis. Further RNA-seq analysis demonstrated that treatment of grifolin on A549 cells led to gene enrichment in MAPK, PI3K/Akt and NF-κB signaling pathways, all of which were inhibited by grifolin according to immunoblotting experiments. Further mechanistical studies disclosed that the expression of a key upstream protein KRAS was also blocked, and the cell death triggered by grifolin could be rescued by a RAS activator ML-099. Moreover, pretreatment of ML-099 on A549 cells could reverse the grifolin-induced downregulation of key proteins in the three aforementioned pathways. These findings indicate that grifolin could induce cell death in A549 cell line by inhibiting KRAS-mediated multiple signaling pathways.

Prenylated Flavanone Enantiomers with α-Glucosidase Inhibitory Activity from the Root Bark of Morus alba.

A focused chemical investigation into the polar fractions of a well-known traditional Chinese medicine called Sang-Bai-Pi (the root bark of Morus alba) yielded a panel of prenylated flavanones. The new compounds were identified as four pairs of enantiomers (1a/1b-4a/4b) featuring the same constitution structure, on the basis of HRMS, NMR and ECD analyses. Several previously reported known racemic co-metabolites were also analyzed and separated by HPLC on chiral columns, and the absolute configurations of pure enantiomers were established via ECD technique for the first time. The inhibition of these isolates against the antidiabetic target α-glycosidase was further tested, with most of them showing decent inhibitory activity compared with the positive control acarbose. The interaction mechanism of two selected compounds (3a & 4b) was explored by kinetics experiment, which revealed a mixed type of inhibition pattern toward the enzyme.

Biological Activity and Sterilization Mechanism of Marine Fungi-derived Aromatic Butenolide Asperbutenolide A Against Staphylococcus aureus.

Marine fungi represent a huge untapped resource of natural products. The bio-activity of a new asperbutenolide A from marine fungus Aspergillus terreus was not well known. In the present study, the minimum inhibitory concentration (MIC) and RNA-Sequencing were used to analyze the bio-activity and sterilization mechanism of asperbutenolide A against clinical pathogenic microbes. The results showed that the MICs of asperbutenolide A against methicillin-resistant Staphylococcus aureus (MRSA) were 4.0-8.0 µg/mL. The asperbutenolide A present poor bio-activity against with candida. The sterilization mechanism of asperbutenolide A against MRSA showed that there were 1426 differentially-expressed genes (DEGs) between the groups of MRSA treated with asperbutenolide A and negative control. Gene Ontology (GO) classification analysis indicated that the DEGs were mainly involved in cellular process, metabolic process, cellular anatomical entity, binding, catalytic activity, etc. Kyoto Encyclopedia of Genes and Genomes (KEGG) classification analysis showed that these DEGs were mainly enriched in amino acid metabolism, carbohydrate metabolism, membrane transport, etc. Moreover, qRT-PCR showed similar trends in the expressions of argF, ureA, glmS and opuCA with the RNA-Sequencing. These results indicated that asperbutenolide A was with ideal bio-activity against with MRSA and could be as a new antibacterial agent.

Anti-inflammatory Polyketides from an Endophytic Fungus Chaetomium sp. UJN-EF006 of Vaccinium bracteatum.

Seven new polyketides including three chromone derivatives (1-3) and four linear ones incorporating a tetrahydrofuran ring (4-7), along with three known compounds (8-10), were obtained from the fermentation of an endophytic fungus (Chaetomium sp. UJN-EF006) isolated from the leaves of Vaccinium bracteatum. The structures of these fungal metabolites have been elucidated by spectroscopic means including MS, NMR and electronic circular dichroism. A preliminary anti-inflammatory screening with the lipopolysaccharide (LPS) induced RAW264.7 cell model revealed moderate NO production inhibitory activity for compounds 1 and 4. In addition, the expression of three LPS-induced inflammatory factors IL-6, iNOS and COX-2 was also blocked by 1 and 4.

Assessment of vertical cooling performance of trees over different surface covers.

Tree-induced cooling benefits are associated with various factors, such as canopy morphology, surface cover, and environmental configuration. However, limited studies have analyzed the sensitivity of tree-induced cooling effects to the combination of such factors. Most studies have focused on 1.5-m cooling performance, and few studies on the variability of the under-tree vertical cooling performance. Therefore, this study aims to investigate the vertical cooling performance of different combinations of trees and surface covers. The study was completed in Chongqing, China, with field experiments capturing vertical air temperature and wind speed at 0.5, 1.0, 1.5, 2.0 and 2.5 m under two typical combinations of "tree + grass" (ComA) and "tree + shrubs" (ComB), and capturing 1.5 m microclimatic environments of a control group with hard pavement without tree shade (REF). The results show that at an average ambient temperature of 33 °C, the maximum air-cooling temperatures for ComA and ComB were 2.46 °C and 1.78 °C, respectively. An increase in the ambient temperature corresponded to a decrease in the cooling effect difference between ComA and ComB. ComA had a maximum vertical temperature difference of 1.01 °C between H1.5m and H2.0m. Between H2.5m and H2.0m, the maximum vertical temperature difference for ComB was 1.64 °C. This study explored the changing patterns of under-tree vertical temperatures under different tree and surface cover combinations, conducive to clarifying the key elements affecting tree cooling performance. The results have implications for accurate thermal comfort assessments and provide a theoretical basis for fine-tuning the design of under-tree spaces.

Coordinating public and government responses to air pollution exposure: A multi-source data fusion approach.

Aligning public demand with government supply of clean air aids in efficient air pollution control and enhancement of public happiness. However, comparative empirical analyses of public and government attention to air quality changes are still sparse due to data and methodological constraints. Here, we adopt multi-source data fusion approaches to assess the impacts of air pollution exposure on public and government attention. Specifically, remote and social sensing data, alongside keywords extracted from textual data, are utilized to quantify air pollution exposure and corresponding public and government attention levels in 273 Chinese cities from 2011 to 2019, and a two-stage least squares regression model is employed to tackle reverse causality issues underlying the exposure-response relationship. Our findings reveal that, on average, a unit increase in PM2.5 levels would result in a 17.7% growth in public attention and a 12.7% rise in government attention, respectively, suggesting that demand-driven public attention tends to be more sensitive to air quality changes than policy-driven government attention. Results for the spatial-temporal heterogeneity further demonstrate that public attention varies across time and space, whereas government attention remains relatively consistent. Additionally, we have identified 116 cities exhibiting disparities between the public and government responses to air quality changes, calling for environmental policy refinements to better serve the needs of residents. This study emphasizes the necessity of public engagement in environmental governance and offers rich policy implications for air pollution control in China.

Removal effect of pollutants from stormwater runoff in shallow bioretention system with gramineous plants.

The bioretention system is one of the most widely used low impact development (LID) facilities with efficient purification capacity for stormwater, and its planting design has been a hot spot for research at home and abroad. In this paper, ryegrass (Lolium perenne L.), bermuda (Cynodon dactylon Linn.), bahiagrass (Paspalum notatum Flugge), and green grass (Cynodon dactylon × C .transadlensis 'Tifdwarf') were chosen as plant species to construct a shallow bioretention system. The growth traits and nutrient absorption ability of four gramineous plants were analyzed. Their tolerance, enrichment, and transportation capacity were also evaluated to compare plant species and their absorptive capacity of heavy metals (Cu, Pb, and Zn). Results showed that the maximum absorption rate (Imax) ranged from 22.1 to 42.4 µg/(g·h) for P and ranged from 65.4 to 104.8 µg/(g·h) for NH4+-N; ryegrass had the strongest absorption capacity for heavy metals and the maximum removal rates of Cu, Pb, and Zn by four grasses were 78.4, 59.4, and 51.3%, respectively; the bioretention cell with ryegrass (3#) was significantly more effective in purifying than the unplanted bioretention cell (1#) during the simulated rainfall test. Overall, the system parameters were optimized to improve the technical application of gramineous plants in the bioretention system.

[Cloning and functional verification of farnesyl pyrophosphate synthase gene(AvFPS) from Aconitum vilmorinianum].

Aconitum vilmorinianum is an authentic and superior medicinal herbal in Yunnan, which is rich in yunaconitine and other diterpene alkaloids. Diterpene alkaloids are its main active components. Farnesyl pyrophosphate synthase(FPS) is a key enzyme in the terpene biosynthetic pathway and plays an important role in diterpene alkaloid biosynthesis. Functional studies of FPS help to reveal the molecular mechanism of diterpene alkaloid biosynthesis. In this study, one FPS gene(AvFPS) was selected based on the transcriptome data of A. vilmorinianum. Its full-length sequence was cloned, and bioinformatic analysis, functional verification, and gene expression analysis were performed. The open reading frame(ORF) of AvFPS was 1 056 bp, encoding 351 amino acids. Its molecular weight was 41 kDa. AvFPS had two typical conserved functional domains of isopentenyl transferase, " DDIMD" and " DDYXD". The recombinant protein of AvFPS was expressed in Escherichia coli, and purified recombinant protein was used for in vitro enzymatic reaction. The results revealed that AvFPS was able to catalyze the synthesis of farnesyl pyrophosphate(FPP). The results of qRT-PCR analysis showed that AvFPS was expressed in the roots, stems, leaves, and flowers of A. vilmorinianum, with the highest expression level in the roots. The expression level of AvFPS was significantly up-regulated by MeJA induction. This study clarified the catalytic function of AvFPS, revealed the expression pattern of AvFPS in different tissue, as well as at different time induced by MeJA, and provided a reference for a deeper understanding of the function of FPS in the biosynthesis of diterpenoid components.

Integration of Metabolomics, Lipidomics, and Proteomics Reveals the Metabolic Characterization of Nonalcoholic Steatohepatitis.

Metabolic dysfunction is associated with nonalcoholic steatohepatitis (NASH) development. However, omics studies investigating metabolic changes in NASH patients are limited. In this study, metabolomics and lipidomics in plasma, as well as proteomics in the liver, were performed to characterize the metabolic profiles of NASH patients. Moreover, the accumulation of bile acids (BAs) in NASH patients prompted us to investigate the protective effect of cholestyramine on NASH. The liver expression of essential proteins involved in FA transport and lipid droplets was significantly elevated in patients with NASH. Furthermore, we observed a distinct lipidomic remodeling in patients with NASH. We also report a novel finding suggesting an increase in the expression of critical proteins responsible for glycolysis and the level of glycolytic output (pyruvic acid) in patients with NASH. Furthermore, the accumulation of branched chain amino acids, aromatic amino acids, purines, and BAs was observed in NASH patients. Similarly, a dramatic metabolic disorder was also observed in a NASH mouse model. Cholestyramine not only significantly alleviated liver steatosis and fibrosis but also reversed NASH-induced accumulation of BAs and steroid hormones. In conclusion, NASH patients were characterized by perturbations in FA uptake, lipid droplet formation, glycolysis, and accumulation of BAs and other metabolites.

High-throughput precision MRI assessment with integrated stack-ensemble deep learning can enhance the preoperative prediction of prostate cancer Gleason grade.

BACKGROUND: To develop and test a Prostate Imaging Stratification Risk (PRISK) tool for precisely assessing the International Society of Urological Pathology Gleason grade (ISUP-GG) of prostate cancer (PCa). METHODS: This study included 1442 patients with prostate biopsy from two centres (training, n = 672; internal test, n = 231 and external test, n = 539). PRISK is designed to classify ISUP-GG 0 (benign), ISUP-GG 1, ISUP-GG 2, ISUP-GG 3 and ISUP GG 4/5. Clinical indicators and high-throughput MRI features of PCa were integrated and modelled with hybrid stacked-ensemble learning algorithms. RESULTS: PRISK achieved a macro area-under-curve of 0.783, 0.798 and 0.762 for the classification of ISUP-GGs in training, internal and external test data. Permitting error ±1 in grading ISUP-GGs, the overall accuracy of PRISK is nearly comparable to invasive biopsy (train: 85.1% vs 88.7%; internal test: 85.1% vs 90.4%; external test: 90.4% vs 94.2%). PSA ≥ 20 ng/ml (odds ratio [OR], 1.58; p = 0.001) and PRISK ≥ GG 3 (OR, 1.45; p = 0.005) were two independent predictors of biochemical recurrence (BCR)-free survival, with a C-index of 0.76 (95% CI, 0.73-0.79) for BCR-free survival prediction. CONCLUSIONS: PRISK might offer a potential alternative to non-invasively assess ISUP-GG of PCa.

PI-RADSAI: introducing a new human-in-the-loop AI model for prostate cancer diagnosis based on MRI.

BACKGROUND: This study aims to develop and validate an artificial intelligence (AI)-aided Prostate Imaging Reporting and Data System (PI-RADSAI) for prostate cancer (PCa) diagnosis based on MRI. METHODS: The deidentified MRI data of 1540 biopsy-naïve patients were collected from four centres. PI-RADSAI is a two-stage, human-in-the-loop AI capable of emulating the diagnostic acumen of subspecialists for PCa on MRI. The first stage uses a UNet-Seg model to detect and segment biopsy-candidate prostate lesions, whereas the second stage leverages UNet-Seg segmentation is trained specifically with subspecialist' knowledge-guided 3D-Resnet to achieve an automatic AI-aided diagnosis for PCa. RESULTS: In the independent test set, UNet-Seg identified 87.2% (628/720) of target lesions, with a Dice score of 44.9% (range, 22.8-60.2%) in segmenting lesion contours. In the ablation experiment, the model trained with the data from three centres was superior (kappa coefficient, 0.716 vs. 0.531) to that trained with single-centre data. In the internal and external tests, the triple-centre PI-RADSAI model achieved an overall agreement of 58.4% (188/322) and 60.1% (92/153) with a referential subspecialist in scoring target lesions; when one-point margin of error was permissible, the agreement rose to 91.3% (294/322) and 97.3% (149/153), respectively. In the paired test, PI-RADSAI outperformed 5/11 (45.5%) and matched the performance of 3/11 (27.3%) general radiologists in achieving a clinically significant PCa diagnosis (area under the curve, internal test, 0.801 vs. 0.770, p < 0.01; external test, 0.833 vs. 0.867, p = 0.309). CONCLUSIONS: Our closed-loop PI-RADSAI outperforms or matches the performance of more than 70% of general readers in the MRI assessment of PCa. This system might provide an alternative to radiologists and offer diagnostic benefits to clinical practice, especially where subspecialist expertise is unavailable.