Implementable Deep Learning for Multi‐sequence Proton MRI Lung Segmentation: A Multi‐center, Multi‐vendor, and Multi‐disease Study

AlexandrosSfakianakis shared this article with you from Inoreader Implementable Deep Learning for Multi‐sequence Proton MRI Lung Segmentation: A Multi‐center, Multi‐vendor, and Multi‐disease Study via Journal of Magnetic Resonance Imaging Background Recently, deep learning via convolutional neural networks (CNNs) has largely superseded conventional methods for proton (1H)-MRI lung segmentation. However, previous deep learning studies have utilized single-center data and limited acquisition parameters. Purpose Develop a generalizable CNN for lung segmentation in 1H-MRI, robust to pathology, acquisition protocol, vendor, and center. Study type Retrospective. Population A total of 809 1H-MRI scans from 258 participants with various pulmonary pathologies (median age (range): 57 (6–85); 42% females) and 31 healthy participants (median age (range): 34 (23–76); 34% females) that were split into training (593 scans (74%); 157 participants (55%)), testing (50 scans (6%); 50 participants (17%)) and external validation (164 scans (20%); 82 participants (28%)) sets. Field Strength/Sequence 1.5-T and 3-T/3D spoiled-gradient recalled and ultrashort echo-time 1H-MRI. Assessment 2D and 3D CNNs, trained on single-center, multi-sequence data, and the conventional spatial fuzzy c-means (SFCM) method were compared to manually delineated expert segmentations. Each method was validated on external data originating from several centers. Dice similarity coefficient (DSC), average boundary Hausdorff distance (Average HD), and relative error (XOR) metrics to assess segmentation performance. Statistical Tests Kruskal–Wallis tests assessed significances of differences between acquisitions in the testing set. Friedman tests with post hoc multiple comparisons assessed differences between the 2D CNN, 3D CNN, and SFCM. Bland–Altman analyses assessed agreement with manually derived lung volumes. A P value of <0.05 was considered statistically significant. Results The 3D CNN significantly outperformed its 2D analog and SFCM, yielding a median (range) DSC of 0.961 (0.880–0.987), Average HD of 1.63 mm (0.65–5.45) and XOR of 0.079 (0.025–0.240) on the testing set and a DSC of 0.973 (0.866–0.987), Average HD of 1.11 mm (0.47–8.13) and XOR of 0.054 (0.026–0.255) on external validation data. Data Conclusion The 3D CNN generated accurate 1H-MRI lung segmentations on a heterogenous dataset, demonstrating robustness to disease pathology, sequence, vendor, and center. Evidence Level 4. Technical Efficacy Stage 1. View on Web

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Multifunctional Two-Dimensional Bi2Se3 Nanodiscs for Anti-Inflammatory Therapy of Inflammatory Bowel Diseases

AlexandrosSfakianakis shared this article with you from Inoreader Multifunctional Two-Dimensional Bi<sub>2</sub>Se<sub>3</sub> Nanodiscs for Anti-Inflammatory Therapy of Inflammatory Bowel Diseases via ScienceDirect Publication Acta Biomaterialia Publication date: Available online 17 February 2023 Source: Acta Biomaterialia Author(s): Cong Zhang, Qingrong Li, Jie Shan, Jianghao Xing, Xiaoyan Liu, Yan Ma, Haisheng Qian, Xulin Chen, Xianwen Wang, Lian-Ming Wu, Yue Yu View on Web

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Downregulation of miR‐193a/b‐3p during HPV‐induced cervical carcinogenesis contributes to anchorage‐independent growth through PI3K/AKT pathway regulators

AlexandrosSfakianakis shared this article with you from Inoreader Downregulation of miR‐193a/b‐3p during HPV‐induced cervical carcinogenesis contributes to anchorage‐independent growth through PI3K/AKT pathway regulators via Journal of Medical Virology Abstract Cervical cancer is caused by a persistent infection with high-risk types of HPV and an accumulation of (epi)genetic alterations in host cell. Acquisition of anchorage-independent growth represents a critical hallmark during HPV-induced carcinogenesis, thereby yielding the most valuable biomarkers for early diagnosis and therapeutic targets. In a previous study, we found that miR-193a-3p and miR-193b-3p were involved in anchorage-independent growth. This study aimed to delineate the role of miR-193a/b-3p in HPV-induced carcinogenesis and to identify their target genes related to anchorage-independent growth. Cell viability and colony formation were assessed in SiHa cancer cells and HPV-16 and -18 immortalized keratinocytes upon miR-193a/b-3p overexpression. Both miRNAs reduced cell growth of all three cell lines in low-attachment conditions and showed a minor effect in adherent conditions. Online target predicting programs and publicly available expression data were used to find ca ndidate mRNAs targets of miR-193a/b-3p. Seven targets showed reduced mRNA expression upon miR-193a/b-3p overexpression. For 3 targets Western blot analysis was also performed, all showing a reduced protein expression. A direct interaction was confirmed using luciferase assays for 6 genes: LAMC1, PTK2, STMN1, KRAS, SOS2, and PPP2R5C, which are PIK3/AKT regulators. All 6 targets were overexpressed in cervical cancers and/or precursor lesions. Together with an oberserved downregulation of phosphorylated-AKT upon miR-193a/b-3p overexpression, this underlines the biological relevance of miR-193a/b-3p downregulation during HPV-induced cervical carcinogenesis. In conclusion, downregulation of miR-193a-3p and miR-193b-3p is functionally involved in the acquisition of HPV-induced anchorage independence by targeting regulators of the PIK3/AKT pathway. This article is protected by copyright. All rights reserved. View on Web

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An integrated strategy to identify COVID‐19 causal genes and characteristics represented by LRRC37A2

AlexandrosSfakianakis shared this article with you from Inoreader An integrated strategy to identify COVID‐19 causal genes and characteristics represented by LRRC37A2 via Journal of Medical Virology ABSTRACT Genome-wide association study (GWAS) could identify host genetic factors associated with coronavirus disease 2019 (COVID-19). The genes or functional DNA elements through which genetic factors affect COVID-19 remain uncharted. The expression quantitative trait locus (eQTL) provides a path to assess the correlation between genetic variations and gene expression. Here, we firstly annotated GWAS data to describe genetic effects, obtaining genome-wide mapped genes. Subsequently, the genetic mechanisms and characteristics of COVID-19 were investigated by an integrated strategy that included three GWAS-eQTL analysis approaches. It was found that 20 genes were significantly associated with immunity and neurological disorders, including prior and novel genes such as OAS3 and LRRC37A2. The findings were then replicated in single-cell datasets to explore the cell-specific expression of causal genes. Furthermore, associations between COVID-19 and neurological disorders were assessed as a cau sal relationship. Finally, the effects of causal protein-coding genes of COVID-19 were discussed using cell experiments. The results revealed some novel COVID-19-related genes to emphasize disease characteristics, offering a broader insight into the genetic architecture underlying the pathophysiology of COVID-19. This article is protected by copyright. All rights reserved. View on Web

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Monitoring of SARS‐CoV‐2 concentration and circulation of variants of concern in wastewater of Leuven, Belgium.

AlexandrosSfakianakis shared this article with you from Inoreader Monitoring of SARS‐CoV‐2 concentration and circulation of variants of concern in wastewater of Leuven, Belgium. via Journal of Medical Virology Abstract Background Wastewater surveillance plays an important role in the management of the COVID-19 pandemic all over the world. Using different wastewater collection points in Leuven, we wanted to investigate the use of wastewater surveillance as an early warning system for an uprise of infections, and as a tool to follow the circulation of specific variants of concern (VOC) in particular geographic areas. Methods Wastewater samples were collected from local neighborhood sewers and from a large regional wastewater treatment plant (WWTP) in the area of Leuven, Belgium. After virus concentration, SARS-CoV-2 RNA was quantified by RT-qPCR and normalized with the human fecal indicator pepper mild mottle virus (PMMoV). A combination of multiplex RT-qPCR assays was used to detect signature mutations of circulating VOCs. Fecal virus shedding of SARS-CoV-2 variants was measured in feces samples of hospitalized patients. Results In two residential sampling sites, a rise in wastewater SARS-CoV-2 concentration preceded peaks in positive cases. In the WWTP, viral load peaks were seen concomitant with the consecutive waves of positive cases caused by the original Wuhan SARS-CoV-2 strain and subsequent VOCs. During the Omicron BA.1 wave, the wastewater viral load increased to a lesser degree, even after normalization of SARS-CoV-2 concentration using PMMoV. This might be attributable to a lower level of fecal excretion of this variant. Circulation of SARS-CoV-2 VOCs Alpha, Delta, Omicron BA1/BA.2 and BA.4/BA.5 could be detected based on the presence of specific key mutations. The shift in variants was noticeable in the wastewater, with key mutations of two different variants being present simultaneously during the transition period. Conclusions Wastewater-based surveillance is a sensitive tool to monitor SARS-CoV-2 circulation levels and VOCs in larger regions. In times of reduced test capacity this can prove to be highly valuable. Differences in excretion levels of various SARS-CoV-2 variants should however be taken into account when using wastewater surveillance to monitor SARS-CoV-2 circulation levels in the population. This article is protected by copyright. All rights reserved. View on Web

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Pustular psoriasis in Malaysia: A review of the Malaysian Psoriasis Registry 2007 – 2018

AlexandrosSfakianakis shared this article with you from Inoreader Pustular psoriasis in Malaysia: A review of the Malaysian Psoriasis Registry 2007 – 2018 via Wiley: Experimental Dermatology: Table of Contents Abstract Background Pustular psoriasis (PP) is an uncommon subtype of psoriasis with distinct genetic features and clinical phenotypes. Patients with PP tend to experience frequent flares and significant morbidity. This study aims to determine the clinical characteristics, comorbidities and treatment of PP patients in Malaysia. Methods This was a cross-sectional study of patients with PP notified to the Malaysian Psoriasis Registry (MPR) between January 2007 to December 2018. Results Of 21,735 psoriasis patients, 148 (0.7%) had pustular psoriasis. Of these, 93 (62.8%) were diagnosed with generalized pustular psoriasis (GPP) and 55 (37.2%) with localized PP (LPP). The mean age for pustular psoriasis onset was 31.71 ± 18.33 years with a male to female ratio of 1:2.1. Patients with PP were more likely to have dyslipidemia (23.6% vs 16.5%, p=0.022), severe disease [Body surface area >10 and/or Dermatology Life Quality Index (DLQI) >10] (64.8% vs 50%, p=0.003) and require systemic therapy (51.4% vs 13.9%, p<0.001) compared to non-PP patients. Patients with PP also suffered greater impairment to their quality of life (DLQI>10, 48.9% vs 40.3%, p=0.046), had more days off school/work (2.06 ± 6.09 vs 0.5 ± 4.91, p=0.004) and a higher mean number of hospitalizations (0.31 ± 0.95 vs 0.05 ± 1.22, p=0.001) in 6 months compared to non-PP patients. Conclusion Overall, 0.7% of psoriasis patients in the MPR had pustular psoriasis. Patients with PP had a higher rate of dyslipidaemia, severe disease, greater impairment of quality of life, and systemic therapy usage compared to other psoriasis subtypes. View on Web

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Nuclear membrane irregularity in high‐grade urothelial carcinoma cells can be measured by using circularity and solidity as morphometric shape definitions in digital image analysis of urinary tract cytology specimens

AlexandrosSfakianakis shared this article with you from Inoreader Nuclear membrane irregularity in high‐grade urothelial carcinoma cells can be measured by using circularity and solidity as morphometric shape definitions in digital image analysis of urinary tract cytology specimens via Cancer Cytopathology Abstract Background The Paris System for Reporting Urine Cytology defines objective (elevated nuclear/cytoplasmic ratio ≥0.7) and subjective (nuclear membrane irregularity, hyperchromicity, and coarse chromatin) cytomorphologic criteria to identify conventional high-grade urothelial carcinoma (HGUC) cells. Digital image analysis allows quantitative and objective measurement of these subjective criteria. In this study, digital image analysis was used to quantitate nuclear membrane irregularity in HGUC cells. Methods Whole-slide images of HGUC urine specimens were acquired, and HGUC nuclei were manually annotated using the open-source bioimage analysis software QuPath. Custom scripts were used to calculate nuclear morphometrics and perform downstream analysis. Results In total, 1395 HGUC cell nuclei were annotated across 24 HGUC specimens (48.1 ± 6.0 nuclei per case) using both pixel-level and smooth annotation approaches. Nuclear membrane irregularity was estimated by calculating nuclear circularity and solidity. Annotating at pixel-level resolution artifactually increases nuclear membrane perimeter, thus smoothing is necessary to better approximate a pathologist's assessment of nuclear membrane irregularity. After smoothing, nuclear circularity and solidity discriminate between HGUC cell nuclei with visually apparent differences in nuclear membrane irregularity. Conclusions Nuclear membrane irregularity defined by The Paris System for Reporting Urine Cytology is inherently subjective. This study identifies nuclear morphometrics that visually correlate with nuclear membrane irregularity. HGUC specimens show intercase variation in nuclear morphometrics, with some nuclei appearing remarkably regular while others show marked irregularity. A small population of irregular nuclei generates most of the intracase variation in nuclear morphometrics. These results highlight nuclear membrane irregularity as an important, but not definitive, cytomorphologic criterion in HGUC diagnosis. View on Web

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