Αρχειοθήκη ιστολογίου

Αλέξανδρος Γ. Σφακιανάκης
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5
Άγιος Νικόλαος Κρήτη 72100
2841026182
6032607174

Κυριακή 19 Φεβρουαρίου 2023

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

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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Recently, deep learning via convolutional neural networks (CNNs) has largely superseded conventional methods for proton (1H)-MRI lung segmentation.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.

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An evaluation of mechanical and biophysical skin parameters at different body locations

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Abstract

Background

Skin is the largest organ in the body, representing an important interface to monitor health and disease. However, there is significant variation in skin properties for different ages, genders and body regions due to the differences in the structure and morphology of the skin tissues. This study aimed to evaluate the use of non-invasive tools to discriminate a range of mechanical and functional skin parameters from different skin sites.

Materials and methods

A cohort of 15 healthy volunteers was recruited following appropriate informed consent. Four well-established CE-marked non-invasive techniques were used to measure four anatomical regions: palm, forearm, sole and lower lumbar L3, using a repeated measures design. Skin parameters included trans-epidermal water loss (TEWL), pH (acidity), erythema, stratum corneum hydration and stiffness and elasticity using Myoton Pro (skin and muscle probe). Differences between body locations for each parameter and the intra-rater reliability between days were evaluated by the same operator.

Results

The results indicate that parameters differed significantly between skin sites. For the Myoton skin probe, the sole recorded the highest stiffness value of 1006 N/m (SD ± 179), while the lower lumbar recorded the least value of 484 N/m (SD ± 160). The muscle indenter Myoton probe revealed the palm's highest value of 754 N/m (± 108), and the lower lumbar recorded the least value of 208 N/m (SD ± 44). TEWL values were lowest on the forearm, averaging 11 g/m2/h, and highest on the palm, averaging 41 g/m2/h. Similar skin hydration levels were recorded in three of the four sites, with the main difference being observed in the sole averaging 13 arbitrary units. Erythema values were characterised by a high degree of inter-subject variation, and no significant differences between sites or sides were observed. The Myoton Pro Skin showed excellent reliability (intra-class correlation coefficients > 0.70) for all sites with except ion of one site right lower back; the Myoton pro muscle probes showed good to poor reliability (0.90–017), the corneometer showed excellent reliability (>0.75) among all the sites tested, and the TEWL showed Good to poor reliability (0.74–0.4) among sites.

Conclusion

The study revealed that using non-invasive methods, the biophysical properties of skin can be mapped, and significant differences in the mechanical and functional properties of skin were observed. These parameters were reliably recorded between days, providing a basis for their use in assessing and monitoring changes in the skin during health and disease.

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

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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

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

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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.

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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

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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.

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

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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.

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

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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.

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The ability of magnetic resonance imaging to predict lymph node metastases and the risk of recurrence in rectal cancer

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Abstract

Aim

This study aimed to examine the diagnostic accuracy and prognostic value of magnetic resonance imaging (MRI) detected lymph nodes in rectal cancer.

Method

We evaluated 806 rectal cancer patients consecutively operated on between 2015 and 2018 at Helsinki University Hospital. In total, 485 patients met the inclusion criteria of presenting with stage I–III disease and were intended for curative treatment at the time of diagnosis. The effect of MRI-detected clinical lymph node status (cN) on cumulative overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS) was calculated using the Kaplan–Meier analysis.

Results

Negative predictive value (NPV) of MRI-lymphnode negativity was 74.8%. Positive predictive value of lymph node metastasis was only 48.6%. In the Kaplan–Meier survival analysis, OS (p = 0.989), DSS (p = 0.911), and DFS (p = 0.109) did not significantly differ according to MRI nodal status. However, cumulative disease-free survival significantly (p < 0.001) differed according to the histopathological lymph node metastasis status (pN).

Conclusions

MRI detected lymph node positivity appears insufficiently precise and cannot predict disease recurrence or survival. Therefore, it should not serve as an independent risk factor when considering neoadjuvant treatment options for rectal cancer patients.

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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

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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.

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Impact of Exercise and Detraining on Signs of Puberty and Selected Inflammatory Markers in Girls with Precocious Puberty

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Purpose We examined the effects of aerobic exercise and detraining on adiponectin, resistin, tumor necrosis factor alpha (TNF-α), white blood cell, and pubertal signs (uterine length, ovarian volume, luteinizing hormone (LH), and follicle-stimulating hormone (FSH)) in girls with central precocious puberty (CPP). Methods Thirty girls with CPP (aged 7-9) were randomly divided into CPP and CPP + Exercise (EX) groups. 15 Healthy age-matched girls without precocious puberty participated for comparison with CPP. Subjects in the CPP + Ex group attended 12 weeks of aerobic exercise protocol three sessions a week. In the baseline, after completing the exercise protocol and after 4 weeks of detraining, all the parameters were measured. In the CPP and healthy groups, all the parameters were measured in all three stages. To measure adiponectin, resistin, and TNF-α, the ELISA method was used. LH and FSH were measured by electrochemiluminescence immunoassay. WBC counts were analyzed by an automated blood cell counter. Analysis of Variance with repeated measures test was used to analyze the results. Results CPP girls have lower adiponectin (P = 0.01) and higher TNF-α levels (P = 0.001) than healthy girls. In the CPP + EX group, after 12 weeks, body weight and fat mass decreased, adiponectin increased significantly (P = 0.02). Resistin (P = 0.02), TNF-α (P = 0.02), neutrophils (P = 0.01), and signs of puberty significantly (P
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