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Abstract Purpose 46,XY disorders of sex development (46,XY DSD) are characterized by incomplete masculinization of genitalia with reduced androgenization. Accurate clinical management remains challenging, especially based solely on physical examination. Targeted next-generation sequencing (NGS) with known pathogenic genes provides a powerful tool for diagnosis efficiency. This study aims to identify the prevalent genetic variants by targeted NGS technology and investigate the diagnostic rate in a large cohort of 46,XY DSD patients, with most of them presenting atypical phenotypes. Methods Two different DSD panels were developed for sequencing purposes, targeting a cohort of 402 patients diagnosed with 46,XY DSD, who were recruited from the Department of Urology at Children’s Hospital, Zhejiang University School of Medicine (Hangzhou, China). The detailed clinical characteristics were evaluated, and peripheral blood was collected for targeted panels to find the patients’ variants. The clinical significance of these variants was annotated according to American College of Medical Genetics and Genomics (ACMG) guidelines. Results A total of 108 variants across 42 genes were found in 107 patients, including 46 pathogenic or likely pathogenic variants, with 45.7%(21/46) being novel. Among these genes, SRD5A2, AR, FGFR1, LHCGR, NR5A1, CHD7 were the most frequently observed. Besides, we also detected some uncommon causative genes like SOS1, and GNAS. Oligogenic variants were also identified in 9 patients, including several combinations PROKR2/FGFR1/CYP11B1, PROKR2/ATRX, PROKR2/AR, FGFR1/LHCGR/POR, FGFR1/NR5A1, GATA4/NR5A1, WNT4/AR, MAP3K1/FOXL2, WNT4/AR, and SOS1/FOXL2. Conclusion The overall genetic diagnostic rate was 11.2%(45/402), with an additional 15.4% (62/402) having variants of uncertain significance. Additionally, trio/duo patients had a higher genetic diagnostic rate (13.4%) compared to singletons (8.6%), with a higher proportion of singletons (15.1%) presenting variants of uncertain significance. In conclusion, targeted gene panels identified pathogenic variants in a Chinese 46,XY DSD cohort, expanding the genetic understanding and providing evidence for known pathogenic genes’ involvement.

Machine Learning (ML), an Artificial Intelligence (AI) technique that includes both Traditional Machine Learning (TML) and Deep Learning (DL), aims to teach machines to automatically learn tasks by inferring patterns from data. It holds significant promise in aiding medical care and has become increasingly important in improving professional processes, particularly in the diagnosis of psoriasis. This paper presents the findings of a systematic literature review focusing on the research and application of ML in psoriasis analysis over the past decade. We summarized 53 publications by searching the Web of Science, PubMed and IEEE Xplore databases and classified them into three categories: (i) lesion localization and segmentation; (ii) lesion recognition; (iii) lesion severity and area scoring. We have presented the most common models and datasets for psoriasis analysis, discussed the key challenges, and explored future trends in ML within this field. Our aim is to suggest directions for subsequent research.

Abstract Shape-memory materials hold great potential to impart medical devices with functionalities useful during implantation, locomotion, drug delivery, and removal. However, their clinical translation is limited by a lack of non-invasive and precise methods to trigger and control the shape recovery, especially for devices implanted in deep tissues. In this study, the application of image-guided high-intensity focused ultrasound (HIFU) heating is tested. Magnetic resonance-guided HIFU triggered shape-recovery of a device made of polyurethane urea while monitoring its temperature by magnetic resonance thermometry. Deformation of the polyurethane urea in a live canine bladder (5 cm deep) is achieved with 8 seconds of ultrasound-guided HIFU with millimeter resolution energy focus. Tissue sections show no hyperthermic tissue injury. A conceptual application in ureteral stent shape-recovery reduces removal resistance. In conclusion, image-guided HIFU demonstrates deep energy penetration, safety and speed.

Abstract Mast cells are phenotypically and functionally heterogeneous, and their state is possibly controlled by local microenvironment. Therefore, specific analyses are needed to understand whether mast cells function as powerful participants or dispensable bystanders in specific diseases. Here, we show that degranulation of mast cells in inflammatory synovial tissues of patients with rheumatoid arthritis (RA) is induced via MAS-related G protein-coupled receptor X2 (MRGPRX2), and the expression of MHC class II and costimulatory molecules on mast cells are upregulated. Collagen-induced arthritis mice treated with a combination of anti-IL-17A and cromolyn sodium, a mast cell membrane stabilizer, show significantly reduced clinical severity and decreased bone erosion. The findings of the present study suggest that synovial microenvironment-influenced mast cells contribute to disease progression and may provide a further mast cell-targeting therapy for RA.

Abstract Excessive host immune responses contribute to severe malaria with high mortality. Here, we show that PRL2 in innate immune cells is highly related to experimental malaria disease progression, especially the development of murine severe malaria. In the absence of PRL2 in myeloid cells, Plasmodium berghei infection results in augmented lung injury, leading to significantly increased mortality. Intravital imaging revealed greater neutrophilic inflammation and NET formation in the lungs of PRL2 myeloid conditional knockout mice. Depletion of neutrophils prior to the onset of severe disease protected mice from NETs associated lung injury, and eliminated the difference between WT and PRL2 CKO mice. PRL2 regulates neutrophil activation and NET accumulation via the Rac-ROS pathway, thus contributing to NETs associated ALI. Hydroxychloroquine, an inhibitor of PRL2 degradation alleviates NETs associated tissue damage in vivo. Our findings suggest that PRL2 serves as an indicator of progression to severe malaria and ALI. In addition, our study indicated the importance of PRL2 in NET formation and tissue injury. It might open a promising path for adjunctive treatment of NET-associated disease.

Eutrophication has become prominent in many lakes of the world, resulting in a continuous rise of suspended particulate organic matter (POM) that can be of vital consequence for water quality and carbon cycling. While the accumulation and decomposition of POM can enhance nutrient cycling at a rate depending on the property of lake-water organic carbon, it is important to identify the source of suspended POM for evaluating eutrophication and carbon burial. Here we analyzed the distribution of stable isotopic ratios (δ13C and δ15N) and the carbon/nitrogen ratio (C/N) in suspended POM in a shallow eutrophic lake of subtropical China, for apportioning the POM sources using Bayesian mixing model. Specifically, we collected seasonal samples of lake-water POM (>0.7 μm) from 20 sites in Yilong Lake from September 2020 to June 2022, as well as six types of modern samples covering the main carbon sources in the catchment. The spatial surveys showed that in the dry year (low water level) the δ13C of POM was more enriched in the western basin than those in the central and eastern basins, while the seasonal surveys showed the most enriched δ13C of POM in September. However, this spatio-temporal heterogeneity disappeared in the wet year (high water level). It was also found that the δ13C, δ15N and C/N values of POM varied significantly with those of phytoplankton across sites and seasons. Application of the MixSIAR model further showed that phytoplankton was the predominant source of POM in Yilong Lake (79.8 ± 13.4 %), but with large annual difference, 68.9 ± 10.3 % in the dry year and 90.7 ± 3.7 % in the wet year. In comparison, the contribution of the other five endmembers was much more moderate. In particular, the proportion of allochthonous organic carbon in POM was relatively low, with terrestrial plants and soils contributing 6.1 ± 4.8 % and 4.3 ± 2.5 % of POM, respectively. Our quantitative evidence for the dominance of the autochthonous source (i.e., phytoplankton) in lake-water POM over time and space suggested a determining role of eutrophication in the composition of lake organic carbon. Therefore, the coupling of algal blooms with organic carbon cycling in inland waters can be enhanced with continuous catchment development and regional warming.

With the rapid growth in the number of EVs, a huge number of EVs are connected to the power grid for charging, which places a great amount of pressure on the stable operation of the power grid. This paper focuses on the development of V2G applications, based on the current research status of V2G technology. Firstly, the standards on V2G applications and some pilot projects involving more representative V2G systems are introduced. Comparing V2G applications with ordered charging and unordered charging, the social and economic benefits of V2G applications are highlighted. Analysis of the social benefits of V2G applications concerns three points: the grid demand response, personalized charging, and the coordination of renewable energy sources. And analysis of the economic benefits of V2G applications is divided into three parties: the grid, the aggregator, and individuals. From the perspective of innovative EVs expanding the application scenarios through V2G technology, V2G applications for commercial EVs, emergency power applications, and vehicle-to-vehicle energy trading are introduced. The current challenges related to V2G applications are presented: users’ willingness to participate in V2G applications, battery loss, charging and discharging tariffs, privacy and security, and power loss. Finally, some research recommendations for the development of V2G applications are given and the current state of research in regard to those recommendations is presented.

Aim: The present study aimed to assess the diagnostic efficacy of contrast-enhanced voiding urosonography (ceVUS) using SonoVue for evaluating duplex kidneys, and to compare it with fluoroscopic voiding cystourethrography (VCUG). Material and methods: Forty-six children with duplex kidneys confirmed by surgical intervention or cystoscopy were included in the study, resulting in a total of 46 duplex kidneys and 46 normal kidneys (138 pyeloureteral units). Results: The overall sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of RBUS for diagnosing duplex kidney disease were 73.91%, 80.43%, 79.07%, and 75.51%, respectively. The diagnostic performance of RBUS and ceVUS in detecting duplex kidney yielded an overall sensitivity, specificity, PPV, and NPV of 89.13%, 84.78%, 85.42%, and 88.64%, respectively. The sensitivity, specificity, PPV, and NPV of VCUG in diagnosing duplex kidney disease were 17.31%, 86.96%, 57.14%, and 51.23%, respectively. For the 42 pyeloureteral units with VUR, Cohen's weighted kappa value for the agreement between ceVUS and VCUG in grading VUR was 0.702 (95% CI, 0.551 ~ 0.854; p <0.05). Conclusions: RBUS effectively diagnoses duplex kidneys with renal pelvic dilation, while ceVUS can further elucidate whether reflux occurs in the upper or lower moiety in cases of duplex kidneys with VUR. Compared to VCUG, both RBUS and ceVUS provide more intuitive diagnoses for duplex kidneys with VUR and ureterocele. Additionally, there is good consistency between ceVUS and VCUG in grading VUR. CeVUS is recommended as an initial evaluation method for patients suspected of having duplex kidneys associated with urinary tract infections. [ABSTRACT FROM AUTHOR]