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PURPOSE: An MRI-based risk calculator (RC) has been recommended for diagnosing clinically significant prostate cancer (csPCa). PSMA PET/CT can detect lesions that are not visible on MRI, and the addition of PSMA PET/CT to MRI may improve diagnostic performance. The aim of this study was to incorporate the PRIMARY score or SUVmax derived from [68Ga]Ga-PSMA-11 PET/CT into the RC and compare these models with MRI-based RC to assess whether this can further reduce unnecessary biopsies. METHODS: A total of 683 consecutive biopsy-naïve men who underwent both [68Ga]Ga-PSMA-11 PET/CT and MRI before biopsy were temporally divided into a development cohort (n = 552) and a temporal validation cohort (n = 131). Three logistic regression RCs were developed and compared: MRI-RC, MRI-SUVmax-RC and MRI-PRIMARY-RC. Discrimination, calibration, and clinical utility were evaluated. The primary outcome was the clinical utility of the risk calculators for detecting csPCa and reducing the number of negative biopsies. RESULTS: The prevalence of csPCa was 47.5% (262/552) in the development cohort and 41.9% (55/131) in the temporal validation cohort. In the development cohort, the AUC of MRI-PRIMARY-RC was significantly higher than that of MRI-RC (0.924 vs. 0.868, p < 0.001) and MRI-SUVmax-RC (0.924 vs. 0.904, p = 0.002). In the temporal validation cohort, MRI-PRIMARY-RC also showed the best discriminative ability with an AUC of 0.921 (95% CI: 0.873-0.969). Bootstrapped calibration curves revealed that the model fit was acceptable. MRI-PRIMARY-RC exhibited near-perfect calibration within the range of 0-40%. DCA showed that MRI-PRIMARY-RC had the greatest net benefit for detecting csPCa compared with MRI-RC and MRI-SUVmax-RC at a risk threshold of 5-40% for csPCa in both the development and validation cohorts. CONCLUSION: The addition of the PRIMARY score to MRI-based multivariable model improved the accuracy of risk stratification prior to biopsy. Our novel MRI-PRIMARY prediction model is a promising approach for reducing unnecessary biopsies and improving the early detection of csPCa.
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The low susceptibility to mastitis of female donkey (jenny) mammary glands and the strong immune properties of donkey milk are acknowledged, but little is known about the genes involved in mammary gland immunity in jennies. Herein, we used RNA-sequencing and bioinformatics analyses to explore jenny mammary gland transcriptomes and detect potential functional differentially expressed (DE) mRNAs related to immunity during four specific developmental stages: foetal (F), pubertal (P), adult parous nonlactation (N) and lactation (L). A total of 2497, 583 and 1820 DE mRNAs were identified in jenny mammary glands at F vs. P, P vs. N, and N vs. L, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genomes (KEGG) analyses revealed numerous GO terms related to immune function, especially between F and P. Seven significantly enriched profiles were identified, among which 497 and 1261 DE mRNAs were upregulated in profiles 19 and 17. Eleven mRNAs were enriched in over 10 KEGG pathways. ß-2-microglobulin (B2M), immunoglobulin heavy constant mu (IGHM), toll like receptor 2 (TLR2), toll like receptor 4 (TLR4) and myeloid differentiation factor 88 (MYD88) were mainly involved in phosphoinositide 3-kinase (PI3K)-Akt signalling, phagosome and nuclear factor kappa-B (NF-kappa B) signalling pathways. The findings provide insight into the molecular features underpinning the low prevalence of intramammary infections (i.e., mastitis) in donkeys.
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Equidae , Mastitis , Femenino , Animales , Humanos , Equidae/genética , Equidae/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Perfilación de la Expresión Génica , Transcriptoma , ARN Mensajero/genética , InmunidadRESUMEN
Despite mare's milk being highly nutritious and beneficial to human health, the effects of different dietary regimens on the lipid profile of mare's milk remain to be completely understood. Herein we employed targeted multiple reaction monitoring-based lipidomics with ultra-high performance liquid chromatography-quadrupole time-of-flight-mass spectrometry to compare the milk lipid profiles of mares fed: pasture grass (P), corn stover and concentrate (H), or cornsilage and concentrate (S). Overall, 461 lipids belonging to 17 subclasses were identified; 261 significantly different lipids were identified on applying the following criteria: false discovery rate-adjusted P < 0.05, variable importance in projection ≥ 1.0, and fold change ≥ 2.0 or ≤ 0.5. The number of significantly different lipids decreased in the order of P > S > H. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis using differential lipids led to the identification of 34, 32, and 31 metabolic pathways on pairwise comparisons between the P and H, P and S, and S and H groups, respectively. The milk of mares in the P group showed significantly higher levels of specific lipids, including triacylglycerols, phosphatidylcholines, and phosphatidylserines, which are known to participate in polyunsaturated fatty acid and lipid digestion and absorption-related metabolic pathways. Altogether, our data provide comprehensive insights into the correlations between feeding systems and quality of mare's milk in terms of bioactive profile.