Hyalinizing clear cell carcinoma of salivary gland: a clinicopathological study of 8 cases

Background and purpose: Hyalinizing clear cell carcinoma (HCCC) of salivary gland is a rare tumor with low-grade malignancy, which usually occurs in minor salivary glands. Due to its rarity, the tumor type is not well known to pathologists and misdiagnosis frequently occurred. The aim of this study was to investigate the histologic, immunophenotypic and molecular features of HCCC. Methods: Eight cases of salivary gland HCCC diagnosed at the Department of Pathology, Fudan University Shanghai Cancer Center from January 2015 to October 2019 were collected. Clinicopathologic characteristics were analyzed, and fluorescence in situ hybridization (FISH) assay was used to detect EWSR1 translocation in tumor tissue. Diagnostic criteria and differential diagnosis were summarized, with a review of the literature. Results: All patients were female, aged 26 to 68 years, and the tumor locations included the oral cavity, nasopharynx, parotid gland and other sites of head and neck. Microscopically, the tumors consisted mainly of clear cells and eosinophilic cells with variable proportions, arranged in nests, sheets and trabeculae. In 1 case, the tumor was composed almost entirely of eosinophilic cells; in 6 cases, obvious nuclear pseudo-inclusion bodies were seen; in 1 case, neoplastic cells were connected to the surface squamous epithelium; in 1 case, the glandular structure was seen in some areas of the tumor; in 3 cases, a sheath of lymphocyte was formed around the tumor nests; in 7 cases, there was a sclerosing or hyalinizing stromal reaction, showing desmoplastic changes; and 1 case featured stoma with myxoid changes. There was no definite keratinization or necrosis in all tumors, and mitotic figures were generally rare. Immunohistochemical staining showed that tumor cells of 8 cases were diffusely positive for AE1/AE3 protein, 7 cases expressed P63, and 7 cases focally expressed low molecular weight keratin CK7 or CAM5.2, however, S-100, calponin, PAX-8 and CD10 were all negative. All tumors showed low proliferative activity, with the Ki-67 proliferation index less than 5%. FISH test revealed EWSR1 translocation in all 8 cases. All patients demonstrated no recurrence or metastasis during the follow up ranging 4-50 months. Conclusions: HCCC of salivary gland is a low-grade malignancy occurring mainly in minor salivary glands, with characteristic histological and molecular features. This cancer type needs to be distinguished with many morphologic mimics of salivary gland. Most cases with salivary HCCC feature a good prognosis

Neonatal invasive candidiasis in low-and-middle-income countries: data from the NeoOBS study

Neonatal invasive candidiasis (NIC) has significant morbidity and mortality. Reports have shown a different profile of those neonates affected with NIC and of fluconazole resistant Candida spp. isolates in low-and-middle-income -countries (LMICs) compared to high-income-countries (HIC). We describe the epidemiology, Candida spp. distribution, treatment and outcomes of neonates with NIC from LMICs enrolled in a global, prospective, longitudinal, observational cohort study (NeoOBS) of hospitalised infants < 60 days postnatal age with sepsis (August 2018-February 2021). 127 neonates from 14 hospitals in 8 countries with Candida spp. isolated from blood culture were included. Median gestational age of affected neonates was 30 weeks (IQR: 28-34) and median birth weight was 1270 g (IQR: 990-1692). Only a minority had high risk criteria, such as being born < 28 weeks, 19% (24/127), or birth weight < 1000 g, 27% (34/127). The most common Candida species were C. albicans (n = 45, 35%), C. parapsilosis (n = 38, 30%) and Candida auris (n = 18, 14%). The majority of C. albicans isolates were fluconazole susceptible, whereas 59% of C. parapsilosis isolates were fluconazole resistant. Amphotericin B was the most common antifungal used [74% (78/105)], followed by fluconazole [22% (23/105)]. Death by day 28 post-enrolment was 22% (28/127). To our knowledge, this is the largest multi-country cohort of NIC in LMICs. Most of the neonates would not have been considered at high risk for NIC in HICs. A substantial proportion of isolates was resistant to first choice fluconazole. Understanding the burden of NIC in LMIC is essential to guide future research and treatment guidelines

Neonatal invasive candidiasis in low- and middle-income countries: Data from the NeoOBS study.

Neonatal invasive candidiasis (NIC) has significant morbidity and mortality. Reports have shown a different profile of those neonates affected with NIC and of fluconazole-resistant Candida spp. isolates in low- and middle-income countries (LMICs) compared to high-income countries (HICs). We describe the epidemiology, Candida spp. distribution, treatment, and outcomes of neonates with NIC from LMICs enrolled in a global, prospective, longitudinal, observational cohort study (NeoOBS) of hospitalized infants <60 days postnatal age with sepsis (August 2018-February 2021). A total of 127 neonates from 14 hospitals in 8 countries with Candida spp. isolated from blood culture were included. Median gestational age of affected neonates was 30 weeks (IQR: 28-34), and median birth weight was 1270 gr (interquartile range [IQR]: 990-1692). Only a minority had high-risk criteria, such as being born <28 weeks, 19% (24/127), or birth weight <1000 gr, 27% (34/127). The most common Candida species were C. albicans (n = 45, 35%), C. parapsilosis (n = 38, 30%), and Candida auris (n = 18, 14%). The majority of C. albicans isolates were fluconazole susceptible, whereas 59% of C. parapsilosis isolates were fluconazole-resistant. Amphotericin B was the most common antifungal used [74% (78/105)], followed by fluconazole [22% (23/105)]. Death by day 28 post-enrollment was 22% (28/127). To our knowledge, this is the largest multi-country cohort of NIC in LMICs. Most of the neonates would not have been considered at high risk for NIC in HICs. A substantial proportion of isolates was resistant to first choice fluconazole. Understanding the burden of NIC in LMIC is essential to guide future research and treatment guidelines

Experimental Identification of Statistical Correlation between Mechanical Properties of FRP Composite

Recent prediction on the heavy statistical correlation between the mechanical properties of fiber reinforced composite (FRP) raises new concerns on the accurate reliability evaluation of composite structures, but such statistical correlation still lacks experimental verification. In this work, an experimental methodology is proposed to determine the statistical correlation between mechanical properties of unidirectional FRP composite. A rectangular shaped carbon fiber reinforced plastic (CFRP) specimen with a circular hole is loaded by tension, and 3D digital image correlation (DIC) is employed to characterize the heterogeneous strain field around the hole. Virtual field method (VFM) is used to derive E11, E22, &nu;12, and G12 of specimens. Specimen configuration considering fiber angle and hole diameter is optimized to achieve accurate determination of correlation coefficients. Experimental results on the linear correlation coefficients between E11, E22, &nu;12, and G12 agree well with previous theoretical predictions

Femtosecond Laser Fabrication of Submillimeter Microlens Arrays with Tunable Numerical Apertures

In recent years, the demand for optical components such as microlenses has been increasing, and various methods have been developed. However, fabrication of submillimeter microlenses with tunable numerical aperture (NA) on hard and brittle materials remains a great challenge using the current methods. In this work, we fabricated a variable NA microlens array with submillimeter size on a silica substrate, using a femtosecond laser-based linear scanning-assisted wet etching method. At the same time, the influence of various processing parameters on the microlens morphology and NA was studied. The NA of the microlenses could be flexibly adjusted in the range of 0.2 to 0.45 by changing the scanning distance of the laser and assisted wet etching. In addition, the imaging and focusing performance tests demonstrated the good optical performance and controllability of the fabricated microlenses. Finally, the optical performance simulation of the prepared microlens array was carried out. The result was consistent with the actual situation, indicating the potential of the submillimeter-scale microlens array prepared by this method for applications in imaging and detection

Clinicopathological and Survival Outcomes of Well-Differentiated Thyroid Carcinoma Undergoing Dedifferentiation: A Retrospective Study from FUSCC

Background. Recently, several studies have reported that dedifferentiation occurs in fatal well-differentiated thyroid cancer (WDTC) cases. This study aimed at investigating the clinicopathological characteristics of WDTC undergoing dedifferentiation. Methods. A total of 63 WDTC patients harboring dedifferentiated phenotype were enrolled in the study. The Kaplan-Meier method and Cox regression analysis were used to perform survival analyses. Harrell index of concordance (C-index) and Akaike information criterion (AIC) were calculated to compare the predictive value for prognosis among several prognostic classification systems. Results. The median cause-specific survival (CSS) of patients was 138 months, with the CSS rate of 64.0% and 53.3% at 5 and 10 years, respectively. Presence of the anaplastic thyroid cancer (ATC) phenotype significantly increased the risk of poor CSS (P=0.033), and age was the only independent risk factor for disease progression (P=0.015). The C-index and AIC of the age, grade, extent, size (AGES) prognostic classification system for the CSS were 0.723 and 59.937, respectively. Conclusions. The presence of dedifferentiated phenotypes can be responsible for the poor outcomes in WDTC patients. The AGES system demonstrates to be an optimal prognostic system for WDTC undergoing dedifferentiation

Pygo2 Associates with MLL2 Histone Methyltransferase and GCN5 Histone Acetyltransferase Complexes To Augment Wnt Target Gene Expression and Breast Cancer Stem-Like Cell Expansion▿

Resent studies have identified Pygopus as a core component of the β-catenin/T-cell factor (TCF)/lymphoid-enhancing factor 1 (LEF) transcriptional activation complex required for the expression of canonical Wg/Wnt target genes in Drosophila. However, the biochemical involvement of mammalian Pygopus proteins in β-catenin/TCF/LEF gene activation remains controversial. In this study, we perform a series of molecular/biochemical experiments to demonstrate that Pygo2 associates with histone-modifying enzymatic complexes, specifically the MLL2 histone methyltransferase (HMT) and STAGA histone acetyltransferase (HAT) complexes, to facilitate their interaction with β-catenin and to augment Wnt1-induced, TCF/LEF-dependent transcriptional activation in breast cancer cells. We identify a critical domain in Pygo2 encompassing the first 47 amino acids that mediates its HMT/HAT interaction. We further demonstrate the importance of this domain in Pygo2's ability to transcriptionally activate both artificial and endogenous Wnt target genes and to expand breast cancer stem-like cells in culture. This work now links mechanistically Pygo2's role in histone modification to its enhancement of the Wnt-dependent transcriptional program and cancer stem-like cell expansion

Neonatal invasive candidiasis in low- and middle-income countries: data from the NeoOBS study

Neonatal invasive candidiasis (NIC) has significant morbidity and mortality. Reports have shown a different profile of those neonates affected with NIC and of fluconazole-resistant Candida spp. isolates in low- and middle-income countries (LMICs) compared to high-income countries (HICs). We describe the epidemiology, Candida spp. distribution, treatment, and outcomes of neonates with NIC from LMICs enrolled in a global, prospective, longitudinal, observational cohort study (NeoOBS) of hospitalized infants <60 days postnatal age with sepsis (August 2018–February 2021). A total of 127 neonates from 14 hospitals in 8 countries with Candida spp. isolated from blood culture were included. Median gestational age of affected neonates was 30 weeks (IQR: 28–34), and median birth weight was 1270 gr (interquartile range [IQR]: 990–1692). Only a minority had high-risk criteria, such as being born <28 weeks, 19% (24/127), or birth weight <1000 gr, 27% (34/127). The most common Candida species were C. albicans (n = 45, 35%), C. parapsilosis (n = 38, 30%), and Candida auris (n = 18, 14%). The majority of C. albicans isolates were fluconazole susceptible, whereas 59% of C. parapsilosis isolates were fluconazole-resistant. Amphotericin B was the most common antifungal used [74% (78/105)], followed by fluconazole [22% (23/105)]. Death by day 28 post-enrollment was 22% (28/127). To our knowledge, this is the largest multi-country cohort of NIC in LMICs. Most of the neonates would not have been considered at high risk for NIC in HICs. A substantial proportion of isolates was resistant to first choice fluconazole. Understanding the burden of NIC in LMIC is essential to guide future research and treatment guidelines