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BACKGROUND: Weibel-Palade bodies (WPBs) are endothelial cell-specific cigar-shaped secretory organelles containing various biologically active molecules. WPBs play crucial roles in thrombosis, hemostasis, angiogenesis, and inflammation. The main content of WPBs is the procoagulant protein vWF (von Willebrand factor). Physical contacts and functional cross talk between mitochondria and other organelles have been demonstrated. Whether an interorganellar connection exists between mitochondria and WPBs is unknown. METHODS: We observed physical contacts between mitochondria and WPBs in human umbilical vein endothelial cells by electron microscopy and living cell confocal microscopy. We developed an artificial intelligence-assisted method to quantify the duration and length of organelle contact sites in live cells. RESULTS: We found there existed physical contacts between mitochondria and WPBs. Disruption of mitochondrial function affected the morphology of WPBs. Furthermore, we found that Rab3b, a small GTPase on the WPBs, was enriched at the mitochondrion-WPB contact sites. Rab3b deficiency reduced interaction between the two organelles and impaired the maturation of WPBs and vWF multimer secretion. CONCLUSIONS: Our results reveal that Rab3b plays a crucial role in mediating the mitochondrion-WPB contacts, and that mitochondrion-WPB coupling is critical for the maturation of WPBs in vascular endothelial cells.
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Corpos de Weibel-Palade , Fator de von Willebrand , Humanos , Corpos de Weibel-Palade/metabolismo , Fator de von Willebrand/metabolismo , Inteligência Artificial , Exocitose , Células Endoteliais da Veia Umbilical Humana/metabolismo , Mitocôndrias/metabolismo , Células CultivadasRESUMO
BACKGROUND: Understanding the genetic mechanisms underlying gray leaf spot (GLS) resistance in maize is crucial for breeding GLS-resistant inbred lines and commercial hybrids. Genome-wide association studies (GWAS) and gene functional annotation are valuable methods for identifying potential SNPs (single nucleotide polymorphism) and candidate genes associated with GLS resistance in maize. RESULTS: In this study, a total of 757 lines from five recombinant inbred line (RIL) populations of maize at the F7 generation were used to construct an association mapping panel. SNPs obtained through genotyping-by-sequencing (GBS) were used to perform GWAS for GLS resistance using a linear mixture model in GEMMA. Candidate gene screening was performed by analyzing the 10 kb region upstream and downstream of the significantly associated SNPs linked to GLS resistance. Through GWAS analysis of multi-location phenotypic data, we identified ten candidate genes that were consistently detected in two locations or from one location along with best linear unbiased estimates (BLUE). One of these candidate genes, Zm00001d003257 that might impact GLS resistance by regulating gibberellin content, was further identified through haplotype-based association analysis, candidate gene expression analysis, and previous reports. CONCLUSIONS: The discovery of the novel candidate gene provides valuable genomic resources for elucidating the genetic mechanisms underlying GLS resistance in maize. Additionally, these findings will contribute to the development of new genetic resources by utilizing molecular markers to facilitate the genetic improvement and breeding of maize for GLS resistance.
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Estudo de Associação Genômica Ampla , Locos de Características Quantitativas , Zea mays/genética , Doenças das Plantas/genética , Resistência à Doença/genética , Melhoramento Vegetal , Polimorfismo de Nucleotídeo Único/genética , FenótipoRESUMO
Background Preoperative local-regional tumor staging of gastric cancer (GC) is critical for appropriate treatment planning. The comparative accuracy of multiparametric MRI (mpMRI) versus dual-energy CT (DECT) for staging of GC is not known. Purpose To compare the diagnostic accuracy of personalized mpMRI with that of DECT for local-regional T and N staging in patients with GC receiving curative surgical intervention. Materials and Methods Patients with GC who underwent gastric mpMRI and DECT before gastrectomy with lymphadenectomy were eligible for this single-center prospective noninferiority study between November 2021 and September 2022. mpMRI comprised T2-weighted imaging, multiorientational zoomed diffusion-weighted imaging, and extradimensional volumetric interpolated breath-hold examination dynamic contrast-enhanced imaging. Dual-phase DECT images were reconstructed at 40 keV and standard 120 kVp-like images. Using gastrectomy specimens as the reference standard, the diagnostic accuracy of mpMRI and DECT for T and N staging was compared by six radiologists in a pairwise blinded manner. Interreader agreement was assessed using the weighted κ and Kendall W statistics. The McNemar test was used for head-to-head accuracy comparisons between DECT and mpMRI. Results This study included 202 participants (mean age, 62 years ± 11 [SD]; 145 male). The interreader agreement of the six readers for T and N staging of GC was excellent for both mpMRI (κ = 0.89 and 0.85, respectively) and DECT (κ = 0.86 and 0.84, respectively). Regardless of reader experience, higher accuracy was achieved with mpMRI than with DECT for both T (61%-77% vs 50%-64%; all P < .05) and N (54%-68% vs 51%-58%; P = .497-.005) staging, specifically T1 (83% vs 65%) and T4a (78% vs 68%) tumors and N1 (41% vs 24%) and N3 (64% vs 45%) nodules (all P < .05). Conclusion Personalized mpMRI was superior in T staging and noninferior or superior in N staging compared with DECT for patients with GC. Clinical trial registration no. NCT05508126 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Méndez and Martín-Garre in this issue.
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Estadiamento de Neoplasias , Neoplasias Gástricas , Tomografia Computadorizada por Raios X , Humanos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Idoso , Tomografia Computadorizada por Raios X/métodos , Gastrectomia/métodos , Adulto , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética Multiparamétrica/métodosRESUMO
BACKGROUND: Vesical Imaging-Reporting and Data System (VI-RADS) is a pathway for the standardized imaging and reporting of bladder cancer staging using multiparametric (mp) MRI. PURPOSE: To investigate additional role of morphological (MOR) measurements to VI-RADS for the detection of muscle-invasive bladder cancer (MIBC) with mpMRI. STUDY TYPE: Retrospective. POPULATION: A total of 198 patients (72 MIBC and 126 NMIBC) underwent bladder mpMRI was included. FIELD STRENGTH/SEQUENCE: 3.0 T/T2-weighted imaging with fast-spin-echo sequence, spin-echo-planar diffusion-weighted imaging and dynamic contrast-enhanced imaging with fast 3D gradient-echo sequence. ASSESSMENT: VI-RADS score and MOR measurement including tumor location, number, stalk, cauliflower-like surface, type of tumor growth, tumor-muscle contact margin (TCM), tumor-longitudinal length (TLL), and tumor cellularity index (TCI) were analyzed by three uroradiologists (3-year, 8-year, and 15-year experience of bladder MRI, respectively) who were blinded to histopathology. STATISTICAL TESTS: Significant MOR measurements associated with MIBC were tested by univariable and multivariable logistic regression (LR) analysis with odds ratio (OR). Area under receiver operating characteristic curve (AUC) with DeLong's test and decision curve analysis (DCA) were used to compared the performance of unadjusted vs. adjusted VI-RADS. A P-value <0.05 was considered statistically significant. RESULTS: TCM (OR 9.98; 95% confidence interval [CI] 4.77-20.8), TCI (OR 5.72; 95% CI 2.37-13.8), and TLL (OR 3.35; 95% CI 1.40-8.03) were independently associated with MIBC at multivariable LR analysis. VI-RADS adjusted by three MORs achieved significantly higher AUC (reader 1 0.908 vs. 0.798; reader 2 0.906 vs. 0.855; reader 3 0.907 vs. 0.831) and better clinical benefits than unadjusted VI-RADS at DCA. Specially in VI-RADS-defined equivocal lesions, MOR-based adjustment resulted in 55.5% (25/45), 70.4% (38/54), and 46.4% (26/56) improvement in accuracy for discriminating MIBC in three readers, respectively. DATA CONCLUSION: MOR measurements improved the performance of VI-RADS in detecting MIBC with mpMRI, especially for equivocal lesions. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.
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Imageamento por Ressonância Magnética , Invasividade Neoplásica , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/patologia , Masculino , Feminino , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética/métodos , Bexiga Urinária/diagnóstico por imagem , Bexiga Urinária/patologia , Estadiamento de Neoplasias , Meios de Contraste , Imageamento por Ressonância Magnética Multiparamétrica/métodos , Idoso de 80 Anos ou mais , Reprodutibilidade dos Testes , Adulto , Curva ROCRESUMO
KEY MESSAGE: This study revealed the identification of a novel gene, Zm00001d042906, that regulates maize ear length by modulating lignin synthesis and reported a molecular marker for selecting maize lines with elongated ears. Maize ear length has garnered considerable attention due to its high correlation with yield. In this study, six maize inbred lines of significant importance in maize breeding were used as parents. The temperate maize inbred line Ye107, characterized by a short ear, was crossed with five tropical or subtropical inbred lines featuring longer ears, creating a multi-parent population displaying significant variations in ear length. Through genome-wide association studies and mutation analysis, the A/G variation at SNP_183573532 on chromosome 3 was identified as an effective site for discriminating long-ear maize. Furthermore, the associated gene Zm00001d042906 was found to correlate with maize ear length. Zm00001d042906 was functionally annotated as a laccase (Lac4), which showed activity and influenced lignin synthesis in the midsection cells of the cob, thereby regulating maize ear length. This study further reports a novel molecular marker and a new gene that can assist maize breeding programs in selecting varieties with elongated ears.
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Lacase , Zea mays , Zea mays/genética , Lacase/genética , Estudo de Associação Genômica Ampla , Lignina , Melhoramento VegetalRESUMO
Flexible electrothermal films are crucial for protecting equipment and systems in cold weather, such as ice blockages in natural gas pipelines and icing on aircraft wings. Therefore, a flexible electric heater is one of the essential devices in industrial operations. One of the main challenges is to develop flexible electrothermal films with low operating voltage, high steady-state temperature, and good mechanical stability. In this study, a flexible electrothermal film based on graphene-patterned structures was manufactured by combining the laser induction method and the transfer printing process. The grid structure design provides accurate real-time monitoring for the application of electrothermal films and shows potential in solving problems related to deicing and clearing ice blockages in pipelines. The flexible electrothermal film can reach a high heating temperature of 165 °C at 15 V and exhibits sufficient heating stability. By employing a simple and efficient method to create a flexible, high-performance electrothermal film, we provide a reliable solution for deicing and monitoring applications.
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BACKGROUND. Pure ground-glass nodules (pGGNs) on chest CT representing invasive adenocarcinoma (IAC) warrant lobectomy with lymph node resection. For pGGNs representing other entities, close follow-up or sublobar resection without node dissection may be appropriate. OBJECTIVE. The purpose of this study was to develop and validate an automated deep learning model for differentiation of pGGNs on chest CT representing IAC from those representing atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), and minimally invasive adenocarcinoma (MIA). METHODS. This retrospective study included 402 patients (283 women, 119 men; mean age, 53.2 years) with a total of 448 pGGNs on noncontrast chest CT that were resected from January 2019 to June 2022 and were histologically diagnosed as AAH (n = 29), AIS (n = 83), MIA (n = 235), or IAC (n = 101). Lung-PNet, a 3D deep learning model, was developed for automatic segmentation and classification (probability of IAC vs other entities) of pGGNs on CT. Nodules resected from January 2019 to December 2021 were randomly allocated to training (n = 327) and internal test (n = 82) sets. Nodules resected from January 2022 to June 2022 formed a holdout test set (n = 39). Segmentation performance was assessed with Dice coefficients with radiologists' manual segmentations as reference. Classification performance was assessed by ROC AUC and precision-recall AUC (PR AUC) and compared with that of four readers (three radiologists, one surgeon). The code used is publicly available (https://github.com/XiaodongZhang-PKUFH/Lung-PNet.git). RESULTS. In the holdout test set, Dice coefficients for segmentation of IACs and of other lesions were 0.860 and 0.838, and ROC AUC and PR AUC for classification as IAC were 0.911 and 0.842. At threshold probability of 50.0% or greater for prediction of IAC, Lung-PNet had sensitivity, specificity, accuracy, and F1 score of 50.0%, 92.0%, 76.9%, and 60.9% in the holdout test set. In the holdout test set, accuracy and F1 score (p values vs Lung-PNet) for individual readers were as follows: reader 1, 51.3% (p = .02) and 48.6% (p = .008); reader 2, 79.5% (p = .75) and 75.0% (p = .10); reader 3, 66.7% (p = .35) and 68.3% (p < .001); reader 4, 71.8% (p = .48) and 42.1% (p = .18). CONCLUSION. Lung-PNet had robust performance for segmenting and classifying (IAC vs other entities) pGGNs on chest CT. CLINICAL IMPACT. This automated deep learning tool may help guide selection of surgical strategies for pGGN management.
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Adenocarcinoma in Situ , Adenocarcinoma , Aprendizado Profundo , Neoplasias Pulmonares , Lesões Pré-Cancerosas , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Invasividade Neoplásica/patologia , Adenocarcinoma/patologia , Pulmão/patologia , Adenocarcinoma in Situ/patologia , Tomografia Computadorizada por Raios X/métodos , Hiperplasia/patologia , Lesões Pré-Cancerosas/patologiaRESUMO
Centella asiatica (L.) Urban is a famous Chinese traditional medicine, which is widely used for treating various chronic inflammatory diseases. Although there are reports that Centella total glycosides exhibit heart-protective properties, our previous experiment showed that it has cardiac toxic effects in zebrafish. The components of Centella total glycosides are complex, so we recommend further research to determine their key components and mechanisms. In this study, sample quantification was done using liquid chromatography-tandem mass spectrometry. The cardiotoxicity of Centella total glycosides, asiaticoside, madecassoside, asiatic acid, and madecassic acid was evaluated using zebrafish and cell models. The zebrafish oxidative stress model and myocarditis model were used to explore further the mechanisms through which cardiotoxicity is achieved. Asiatic acid and madecassic acid caused zebrafish cardiotoxicity and H9C2 cell death. However, no toxicity effects were observed for asiaticoside and madecassoside in zebrafish, until the solution was saturated. The results from the cell model study showed that asiatic acid and madecassic acid changed the expression of apoptosis-related genes in myocardial cells. In the zebrafish model, high concentrations of these components raised the levels of induced systemic inflammation, neutrophils gathered in the heart, and oxidative stress injury. Asiatic acid and madecassic acid are the main components causing cardiotoxicity in zebrafish. This may be due to enhanced inflammation and reactive oxygen species injury, which causes myocardial cell apoptosis, which further leads to cardiac toxicity.
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Cardiotoxicidade , Centella , Inflamação , Estresse Oxidativo , Triterpenos Pentacíclicos , Espécies Reativas de Oxigênio , Triterpenos , Peixe-Zebra , Animais , Triterpenos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Inflamação/induzido quimicamente , Centella/química , Apoptose/efeitos dos fármacos , Miocardite/induzido quimicamente , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Linhagem CelularRESUMO
Tassel weight (TW) is a crucial agronomic trait that significantly affects pollen supply and grain yield development in maize breeding. To improve maize yield and develop new varieties, a comprehensive understanding of the genetic mechanisms underlying tassel weight is essential. In this study, tropical maize inbred lines, namely CML312, CML373, CML444, and YML46, were selected as female parents and crossed with the elite maize inbred line Ye107, which served as the common male parent, to develop a multi-parent population comprising four F8 recombinant inbred line (RIL) subpopulations. Using 6616 high-quality single nucleotide polymorphism (SNP) markers, we conducted genome-wide association analysis (GWAS) and genomic selection (GS) on 642 F8 RILs in four subpopulations across three different environments. Through GWAS, we identified 16 SNPs that were significantly associated with TW, encompassing two stable loci expressed across multiple environments. Furthermore, within the candidate regions of these SNPs, we discovered four novel candidate genes related to TW, namely Zm00001d044362, Zm00001d011048, Zm00001d011049, and Zm00001d031173 distributed on chromosomes 1, 3, and 8, which have not been previously reported. These genes are involved in processes such as signal transduction, growth and development, protein splicing, and pollen development, all of which play crucial roles in inflorescence meristem development, directly affecting TW. The co-localized SNP, S8_137379725, on chromosome 8 was situated within a 16.569 kb long terminal repeat retrotransposon (LTR-RT), located 22.819 kb upstream and 26.428 kb downstream of the candidate genes (Zm00001d011048 and Zm00001d011049). When comparing three distinct GS models, the BayesB model demonstrated the highest accuracy in predicting TW. This study establishes the theoretical foundation for future research into the genetic mechanisms underlying maize TW and the efficient breeding of high-yielding varieties with desired tassel weight through GS.
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Estudo de Associação Genômica Ampla , Inflorescência , Inflorescência/genética , Locos de Características Quantitativas , Zea mays/genética , Melhoramento Vegetal , Fenótipo , Polimorfismo de Nucleotídeo ÚnicoRESUMO
A catalytic enantioselective polycyclization of tertiary enamides with terminal silyl enol ethers has been developed by virtue of Cu(OTf)2 catalysis with a novel spiropyrroline-derived oxazole (SPDO) ligand. This tandem reaction offers an effective approach to assemble bicyclic and tricyclic N-heterocycles bearing both aza- and oxa-quaternary stereogenic centers, which are primal subunits in a range of natural alkaloids. Strategic application of this methodology and a late-stage radical cyclization as key steps have been showcased in the concise total synthesis of (-)-cephalocyclidin A.
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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.
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Aprendizado Profundo , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/cirurgia , Gradação de Tumores , Próstata/diagnóstico por imagem , Próstata/cirurgia , Próstata/patologia , Imageamento por Ressonância MagnéticaRESUMO
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.
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Próstata , Neoplasias da Próstata , Masculino , Humanos , Próstata/patologia , Neoplasias da Próstata/patologia , Imageamento por Ressonância Magnética/métodos , Inteligência Artificial , Biópsia , Estudos Retrospectivos , Biópsia Guiada por Imagem/métodosRESUMO
BACKGROUND: To investigate the predictive ability of high-throughput MRI with deep survival networks for biochemical recurrence (BCR) of prostate cancer (PCa) after prostatectomy. METHODS: Clinical-MRI and histopathologic data of 579 (train/test, 463/116) PCa patients were retrospectively collected. The deep survival network (iBCR-Net) is based on stepwise processing operations, which first built an MRI radiomics signature (RadS) for BCR, and predicted the T3 stage and lymph node metastasis (LN+) of tumour using two predefined AI models. Subsequently, clinical, imaging and histopathological variables were integrated into iBCR-Net for BCR prediction. RESULTS: RadS, derived from 2554 MRI features, was identified as an independent predictor of BCR. Two predefined AI models achieved an accuracy of 82.6% and 78.4% in staging T3 and LN+. The iBCR-Net, when expressed as a presurgical model by integrating RadS, AI-diagnosed T3 stage and PSA, can match a state-of-the-art histopathological model (C-index, 0.81 to 0.83 vs 0.79 to 0.81, p > 0.05); and has maximally 5.16-fold, 12.8-fold, and 2.09-fold (p < 0.05) benefit to conventional D'Amico score, the Cancer of the Prostate Risk Assessment (CAPRA) score and the CAPRA Postsurgical score. CONCLUSIONS: AI-aided iBCR-Net using high-throughput MRI can predict PCa BCR accurately and thus may provide an alternative to the conventional method for PCa risk stratification.
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Neoplasias da Próstata , Masculino , Humanos , Estudos Retrospectivos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Próstata/patologia , Antígeno Prostático Específico , Prostatectomia/métodos , Hidrolases , Imageamento por Ressonância Magnética/métodos , Medição de RiscoRESUMO
BACKGROUND: Leaf angle is a key trait for maize plant architecture that plays a significant role in its morphological development, and ultimately impacting maize grain yield. Although many studies have been conducted on the association and localization of genes regulating leaf angle in maize, most of the candidate genes identified are associated with the regulation of ligule-ear development and phytohormone pathways, and only a few candidate genes have been reported to enhance the mechanical strength of leaf midrib and vascular tissues. RESULTS: To address this gap, we conducted a genome-wide association study (GWAS) using the leaf angle phenotype and genotyping-by-sequencing data generated from three recombinant inbred line (RIL) populations of maize. Through GWAS analysis, we identified 156 SNPs significantly associated with the leaf angle trait and detected a total of 68 candidate genes located within 10 kb upstream and downstream of these individual SNPs. Among these candidate genes, Zm00001d045408, located on chromosome 9 emerged as a key gene controlling the angles of both the ear leaf and the second leaf above the ear leaf. Notably, this new gene's homolog in Arabidopsis promotes cell division and vascular tissue development. Further analysis revealed that a SNP transversion (G/T) at 7.536 kb downstream of the candidate gene Zm00001d045408 may have caused a reduction in leaf angles of the ear and the second leaf above the ear leaf. Our analysis of the 10 kb region downstream of this candidate gene revealed a 4.337 kb solo long-terminal reverse transcription transposon (solo LTR), located 3.112 kb downstream of Zm00001d045408, with the SNP located 87 bp upstream of the solo LTR. CONCLUSIONS: In summary, we have identified a novel candidate gene, Zm00001d045408 and a solo LTR that are associated with the angles of both the ear leaf and the second leaf above the ear leaf. The future research holds great potential in exploring the precise role of newly identified candidate gene in leaf angle regulation. Functional characterization of this gene can help in gaining deeper insights into the complex genetic pathways underlying maize plant architecture.
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Estudo de Associação Genômica Ampla , Locos de Características Quantitativas , Mapeamento Cromossômico , Zea mays/metabolismo , Fenótipo , Folhas de Planta/metabolismo , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
OBJECTIVE: To test the impact of the fully integrated Smart Beginnings model on parental support of cognitive stimulation from 6 to 24 months across infancy and toddlerhood. STUDY DESIGN: This was a single-blind, 2-site randomized clinical trial of the Smart Beginnings intervention. Enrollment took place at birth in postpartum units of hospitals in New York City and Pittsburgh, Pennsylvania, with a consecutive sample of 403 mother-infant dyads. Smart Beginnings combines a Video Interaction Project-14-session universal primary prevention program delivered in the pediatric clinic at the time of well-child visits birth-36 months-with potential for Family Check-Up-3-4 sessions targeted secondary prevention home-visiting program. The principal outcome was parental support of cognitive stimulation assessed via parent survey and video-recorded observations of parent-child interactions. Ordinary least squares and mixed effects regressions were conducted. RESULTS: Families were mostly Black/African-American (50%) or Latinx (42%); all were Medicaid eligible (100%). Smart Beginnings significantly promoted cognitive stimulation during infancy and toddlerhood for most survey outcomes across time, including StimQ common total (effect size [ES] = 0.25, P = .01) and READ Quantity (ES = .19, P = .04) and Quality (ES = .30, P = .001). For the observations, the impact of Smart Beginnings varied by time, with significant impacts at 6 (ES = 0.37-.40, P < .001) and 24 (ES = 0.27-.30, P < .001) months, but not 18 months. CONCLUSIONS: Smart Beginnings positively promotes cognitive stimulation from infancy through toddlerhood using the integrated model. This study adds to the body of research showing preventive interventions in pediatric primary care and home visiting can support early relational health including parental support of cognitive stimulation. TRIAL REGISTRATION: NCT02459327.
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Desenvolvimento Infantil , Pais , Recém-Nascido , Feminino , Lactente , Criança , Humanos , Método Simples-Cego , Pais/psicologia , Mães , CogniçãoRESUMO
BACKGROUND: The relationship between tumor and muscle layer in the vesical imaging-reporting and data system (VI-RADS) 3 is ambiguous, and there is a lack of preoperative and non-invasive procedures to detect muscle invasion in VI-RADS 3. PURPOSE: To develop a nomogram based on MRI features for detecting muscle invasion in VI-RADS 3. STUDY TYPE: Retrospective. POPULATION: 235 cases (Age: 67.5 ± 11.5 years) with 11.9% females were randomly divided into a training cohort (n = 164) and a validation cohort (n = 71). FIELD STRENGTH/SEQUENCE: 3T, T2-weighted imaging (turbo spin-echo), diffusion-weighted imaging (breathing-free spin echo), and dynamic contrast-enhanced imaging (gradient echo). ASSESSMENT: 3 features were selected from the training cohort, including tumor contact length greater than maximum tumor diameter (TCL > Dmax), flat tumor morphology, and lower standard deviation of apparent diffusion coefficient (ADCSD ). Three readers assessed VI-RADS scores and the tumor morphology. STATISTICAL TESTS: Interobserver agreement was assessed by Kappa analysis. Features for final analysis were selected by logistic regression. The performance of the nomogram was evaluated by the receiver operating characteristic curve, decision curve analysis, and calibration curve. RESULTS: TCL > Dmax, flat morphology, and lower ADCSD were the independent risk factors for muscle invasive in VI-RADS 3. The AUCs, accuracy, sensitivity, and specificity of the nomogram 1 composed of three features for detecting muscle invasion were 0.852 (95% CI: 0.793-0.912), 0.756, 0.917, and 0.663 in the training cohort, and 0.885 (95% CI: 0.801-0.969), 0.817, 0.900, and 0.784 in the validation cohort. The nomogram 2 without ADCSD has nearly the same performance as the nomogram 1. DATA CONCLUSION: Nomogram can be an efficient tool for preoperative detection of muscle invasion in VI-RADS 3. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.
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BACKGROUND: The high level of expertise required for accurate interpretation of prostate MRI. PURPOSE: To develop and test an artificial intelligence (AI) system for diagnosis of clinically significant prostate cancer (CsPC) with MRI. STUDY TYPE: Retrospective. SUBJECTS: One thousand two hundred thirty patients from derivation cohort between Jan 2012 and Oct 2019, and 169 patients from a publicly available data (U-Net: 423 for training/validation and 49 for test and TrumpeNet: 820 for training/validation and 579 for test). FIELD STRENGTH/SEQUENCE: 3.0T/scanners, T2 -weighted imaging (T2 WI), diffusion-weighted imaging, and apparent diffusion coefficient map. ASSESSMENT: Close-loop AI system was trained with an Unet for prostate segmentation and a TrumpetNet for CsPC detection. Performance of AI was tested in 410 internal and 169 external sets against 24 radiologists categorizing into junior, general and subspecialist group. Gleason score >6 was identified as CsPC at pathology. STATISTICAL TESTS: Area under the receiver operating characteristic curve (AUC-ROC); Delong test; Meta-regression I2 analysis. RESULTS: In average, for internal test, AI had lower AUC-ROC than subspecialists (0.85 vs. 0.92, P < 0.05), and was comparable to junior (0.84, P = 0.76) and general group (0.86, P = 0.35). For external test, both AI (0.86) and subspecialist (0.86) had higher AUC than junior (0.80, P < 0.05) and general reader (0.83, P < 0.05). In individual, it revealed moderate diagnostic heterogeneity in 24 readers (Mantel-Haenszel I2 = 56.8%, P < 0.01), and AI outperformed 54.2% (13/24) of readers in summary ROC analysis. In multivariate test, Gleason score, zonal location, PI-RADS score and lesion size significantly impacted the accuracy of AI; while effect of data source, MR device and parameter settings on AI performance is insignificant (P > 0.05). DATA CONCLUSION: Our AI system can match and to some case exceed clinicians for the diagnosis of CsPC with prostate MRI. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.
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Imageamento por Ressonância Magnética , Neoplasias da Próstata , Masculino , Humanos , Imageamento por Ressonância Magnética/métodos , Neoplasias da Próstata/patologia , Inteligência Artificial , Estudos Retrospectivos , Imagem de Difusão por Ressonância Magnética/métodosRESUMO
Core-shell microspheres refer to duo-layer or multilayer microspheres, which are widely used in drug delivery, microreactors, etc. Accurate manipulation of microspheres is a research hot spot, while traditional manipulation methods including ultrasonic manipulation and laser manipulation still face some limitations. In this study, magnetic core-shell microspheres were adopted to realize the accurate manipulation of microspheres. Combined with microfluidic technology, polystyrene sulfonic acid (PSSA)/Fe3O4 magnetic fluid was utilized as the core material and photosensitive acrylic resin became the shell material. After UV curing, a magnetic core-shell microsphere with an average size of 55 µm could be achieved, and the diameter was uniform and controllable. By adjusting the flow rate of the dispersed phase, the dual-core microspheres with different core particle sizes that ranged from 9.3 to 28.4 µm could be prepared. Experimental results showed that the prepared Fe3O4/acrylic resin core-shell microspheres can be used as functionalized microspheres that have good magnetic response properties and self-assembly ability. In addition, the magnetic manipulation and self-assembly of the prepared core-shell microspheres were presented with different external magnetic fields. The magnetic core-shell microspheres have shown great potential in the fields of biomedical engineering and targeted delivery of drugs.
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BACKGROUND: Maternal stress has negative consequences on infant behavioral development, and COVID-19 presented uniquely stressful situations to mothers of infants born during the pandemic. We hypothesized that mothers with higher levels of perceived stress during the pandemic would report higher levels of infant regulatory problems including crying and interrupted sleep patterns. METHODS: As part 6 sites of a longitudinal study, mothers of infants born during the pandemic completed the Perceived Stress Scale, the Brief Infant Sleep Questionnaire, and an Infant Crying survey at 6 (n = 433) and 12 (n = 344) months of infant age. RESULTS: Maternal perceived stress, which remained consistent at 6 and 12 months of infant age, was significantly positively correlated with time taken to settle infants. Although maternal perceived stress was not correlated with uninterrupted sleep length, time taken to put the infant to sleep was correlated. Perceived stress was also correlated with the amount of infant crying and fussiness reported at 6 months. CONCLUSIONS: Mothers who reported higher levels of perceived stress during the pandemic reported higher levels of regulatory problems, specifically at 6 months. Examining how varying levels of maternal stress and infant behaviors relate to overall infant developmental status over time is an important next step. IMPACT: Women giving birth during the COVID-19 pandemic who reported higher levels of stress on the Perceived Stress Scale also reported higher levels of infant fussiness and crying at 6 months old, and more disruptive sleep patterns in their infants at 6 months and 12 months old. Sleeping problems and excessive crying in infancy are two regulatory problems that are known risk factors for emotional and behavioral issues in later childhood. This paper is one of the first studies highlighting the associations between maternal stress and infant behaviors during the COVID-19 pandemic.
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COVID-19 , Pandemias , Lactente , Humanos , Feminino , Gravidez , Criança , Estudos Longitudinais , Comportamento do Lactente/psicologia , Mães/psicologia , Choro/psicologia , Estresse Psicológico/etiologiaRESUMO
OBJECTIVES: To describe the specific MRI characteristics of different pathologic subtypes of esophageal carcinoma (EC) METHODS: This prospective study included EC patients who underwent esophageal MRI and esophagectomy between April 2015 and October 2021. Pathomorphological characteristics of EC such as localized type (LT), ulcerative type (UT), protruding type (PT), and infiltrative type (IT) were assessed by two radiologists relying on the imaging characteristics of tumor, especially the specific imaging findings on the continuity of the mucosa overlying the tumor, the opposing mucosa, mucosa linear thickening, and transmural growth pattern. Intraclass correlation coefficients (ICC) were calculated for the consistency between two readers. The associations of imaging characteristics with different pathologic subtypes were assessed using multilogistic regression model (MLR). RESULTS: A total of 201 patients were identified on histopathology with a high inter-reader agreement (ICC = 0.991). LT showed intact mucosa overlying the tumor. IT showed transmural growth pattern extending from the mucosa to the adventitia and a "sandwich" appearance. The remaining normal mucosa on the opposing side was linear and nodular in UT. PT showed correlation with T1 staging and grade 1; IT showed correlation with T3 staging and grades 2-3. Four MLR models showed high predictive performance on the test set with AUCs of 0.94 (LT), 0.87 (PT), 0.96 (IT), and 0.97 (UT), respectively, and the predictors that contributed most to the models matched the four specific characteristics. CONCLUSIONS: Different pathologic subtypes of EC displayed specific MR imaging characteristics, which could help predict T staging and the degree of pathological differentiation. CLINICAL RELEVANCE STATEMENT: Different pathologic subtypes of esophageal carcinoma displayed specific MR imaging characteristics, which correspond to differences in the degree of differentiation, T staging, and sensitivity to radiotherapy, and could also be one of the predictive factors of cause-specific survival and local progression-free rates. KEY POINTS: Different types of EC had different characteristics on MR images. A total of 91/95 (96%) LTEC showed intact mucosa over the tumor, while masses or nodules are specific to PTEC; 21/27 (78%) ITEC showed a "sandwich" sign; and 33/35 (60%) UTEC showed linear and nodular opposing mucosa. In the association of tumor type with degree of differentiation and T staging, PTEC was predominantly associated with T1 and grade 1, and ITEC was associated with T3 and grades 2-3, while LTEC and UECT were likewise primarily linked with T2-3 and grades 2-3.