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ObjectiveTo develop a semi-automatic model integrating radiomics, deep learning, and clinical features for Bone Metastasis (BM) prediction in prostate cancer (PCa) patients using Biparametric MRI (bpMRI) images.MethodsA retrospective study included 414 PCa patients (BM, n=136; NO-BM, n=278) from two institutions (Center 1, n=318; Center 2, n=96) between January 2016 and December 2022. MRI scans were confirmed with BM status via PET-CT or ECT pre-treatment. Tumor areas on bpMRI images were delineated as tumor’s region of interest (ROI) using auto-delineation tumor models, evaluated with Dice similarity coefficient (DSC). Samples were auto-sketched, refined, and used to train the ResNet BM prediction model. Clinical, radiomics, and deep learning data were synthesized into the ResNet-C model, evaluated using receiver operating characteristic (ROC).ResultsThe auto-segmentation model achieved a DSC of 0.607. Clinical BM prediction’s internal validation had an accuracy (ACC) of 0.650 and area under the curve (AUC) of 0.713; external cohort had an ACC of 0.668 and AUC of 0.757. The deep learning model yielded an ACC of 0.875 and AUC of 0.907 for the internal, and ACC of 0.833 and AUC of 0.862 for the external cohort. The Radiomics model registered an ACC of 0.819 and AUC of 0.852 internally, and ACC of 0.885 and AUC of 0.903 externally. ResNet-C demonstrated the highest ACC of 0.902 and AUC of 0.934 for the internal, and ACC of 0.885 and AUC of 0.903 for the external cohort.ConclusionThe ResNet-C model, utilizing bpMRI scanning strategy, accurately assesses bone metastasis (BM) status in newly diagnosed prostate cancer (PCa) patients, facilitating precise treatment planning and improving patient prognoses.

Aberrant alternative splicing (AS) events have been identified in a variety of cancers. Although somatic mutations of splicing factors and dysregulation of RNA-binding proteins (RBPs) have been linked to AS and tumor malignancy, it remains unclear how upstream mechanisms contribute to cancer development via alternative gene splicing. In this issue of the JCI, Wenrui Zhang and colleagues identified the role of asparagine endopeptidase (AEP), an intracellular cysteine endopeptidase, in promoting solid tumor-associated RNA splicing. The authors demonstrated that tumor environmental factors such as oxygen and nutrient deprivation induce the activity of AEP in a HIFIA-dependent manner. The activated AEP, in turn, cleaves an RNA helicase DDX3X to promote its nuclear retention. The authors further showed that this DDX3X nuclear fraction engages with splicing machinery to induce AS events in several cancer cells. These findings suggest that targeting an AEP-dependent aberrant RNA splicing cascade may facilitate therapeutics for solid tumors., Aberrant RNA splicing in cancers Alternative splicing (AS) is a critical cellular process that contributes to the encoding capacity of transcriptomes of eukaryotic cells (1). Recently, high-throughput sequencing and genome-wide [...]

The influence of frequency characteristics of devices is complex. The effects of AlN barrier thickness, gate length, gate-drain spacing and work function on the frequency characteristics of AlN/ β-Ga2O3 high electron mobility transistor (HEMT) were studied by Sentaurus TCAD in this paper. The following conclusions are obtained: as the thickness of the AlN barrier layer increases from 10 nm to 25 nm, the cutoff frequency (fT) and maximum oscillation frequency (fmax ) rise by 18 and 17 GHz respectively. The decrease of gate capacitance is the main reason for the increase of fT . Furthermore, it was found that the thinner barrier layer enhanced the gate's ability to control the channel electrons. When the gate length is scaled down from 0. 9 μm to 0. 1 μm, fT and fmax increase by 84 and 98 GHz, respectively, representing a far more profound influence on frequency characteristics than the barrier layer thickness. However, when the gate length fell below 0. 1 μm, short-channel effects emerged. As the gate-drain spacing increase, fT exhibits a slight decrease. Coupled with the concurrent reduction in source resistance, this led to a synchronized trend in fmax and fT only when the gate-source voltage (VGS ) exceeds - 1. 2 V. The work function, on the other hand, has minimal impacts on fT and fmax, but an increase in the work function positively influenced the device' s pinch-off characteristics. In summary, this paper indicates that by shortening the gate length while concurrently augmenting the thickness of the AlN barrier layer, gate-drain spacing, and work function, one can enhance the frequency characteristics while also improving the pinch-off characteristics of the device, which has certain guiding significance for the design of HEMT devices. [ABSTRACT FROM AUTHOR]

Although maternal antibodies protect newborn babies from infection.sup.1,2, little is known about how protective antibodies are induced without prior pathogen exposure. Here we show that neonatal mice that lack the capacity to produce IgG are protected from infection with the enteric pathogen enterotoxigenic Escherichia coli by maternal natural IgG antibodies against the maternal microbiota when antibodies are delivered either across the placenta or through breast milk. By challenging pups that were fostered by either maternal antibody-sufficient or antibody-deficient dams, we found that IgG derived from breast milk was crucial for protection against mucosal disease induced by enterotoxigenic E. coli. IgG also provides protection against systemic infection by E. coli. Pups used the neonatal Fc receptor to transfer IgG from milk into serum. The maternal commensal microbiota can induce antibodies that recognize antigens expressed by enterotoxigenic E. coli and other Enterobacteriaceae species. Induction of maternal antibodies against a commensal Pantoea species confers protection against enterotoxigenic E. coli in pups. This role of the microbiota in eliciting protective antibodies to a specific neonatal pathogen represents an important host defence mechanism against infection in neonates. Neonatal mice are protected against infection with the enteric pathogen enterotoxigenic Escherichia coli by maternally derived natural antibodies as well as by maternal commensal microbiota that induce antibodies that recognize antigens expressed by Enterobacteriaceae., Author(s): Wen Zheng [sup.1] , Wenjing Zhao [sup.2] [sup.3] , Meng Wu [sup.1] , Xinyang Song [sup.1] , Florence Caro [sup.3] , Ximei Sun [sup.1] , Francesca Gazzaniga [sup.1] , [...]

The metabolic pathways encoded by the human gut microbiome constantly interact with host gene products through numerous bioactive molecules.sup.1. Primary bile acids (BAs) are synthesized within hepatocytes and released into the duodenum to facilitate absorption of lipids or fat-soluble vitamins.sup.2. Some BAs (approximately 5%) escape into the colon, where gut commensal bacteria convert them into various intestinal BAs.sup.2 that are important hormones that regulate host cholesterol metabolism and energy balance via several nuclear receptors and/or G-protein-coupled receptors.sup.3,4. These receptors have pivotal roles in shaping host innate immune responses.sup.1,5. However, the effect of this host-microorganism biliary network on the adaptive immune system remains poorly characterized. Here we report that both dietary and microbial factors influence the composition of the gut BA pool and modulate an important population of colonic FOXP3.sup.+ regulatory T (T.sub.reg) cells expressing the transcription factor ROR[gamma]. Genetic abolition of BA metabolic pathways in individual gut symbionts significantly decreases this T.sub.reg cell population. Restoration of the intestinal BA pool increases colonic ROR[gamma].sup.+ T.sub.reg cell counts and ameliorates host susceptibility to inflammatory colitis via BA nuclear receptors. Thus, a pan-genomic biliary network interaction between hosts and their bacterial symbionts can control host immunological homeostasis via the resulting metabolites. Both dietary and microbial factors influence the composition of the gut bile acid pool, which in turn modulates the frequencies and functionalities of ROR[gamma]-expressing colonic FOXP3.sup.+ regulatory T cells, contributing to protection from inflammatory colitis., Author(s): Xinyang Song [sup.1] , Ximei Sun [sup.1] , Sungwhan F. Oh [sup.1] [sup.2] , Meng Wu [sup.1] , Yanbo Zhang [sup.1] , Wen Zheng [sup.1] , Naama Geva-Zatorsky [sup.1] [...]