Hyperglycemia-simulating environment attenuated experimentally induced calcification in cultured human aortic valve interstitial cells.

Objectives: The role of diabetes mellitus as a risk factor for the development of calcific aortic valve disease has not been fully clarified. Aortic valve interstitial cells (VICs) have been suggested to be crucial for calcification of the valve. Induced calcification in cultured VICs is a good in vitro model for aortic valve calcification. The purpose of this study was to investigate whether increased glucose levels increase experimentally induced calcification in cultured human VICs. Design: VICs were isolated from explanted calcified aortic valves after valve replacement. Osteogenic medium induced calcification of cultured VICs at different glucose levels (5, 15, and 25 mM). Calcium deposits were visualized using Alizarin Red staining and measured spectrophotometrically. Results: The higher the glucose concentration, the lower the level of calcification. High glucose (25 mM) reduced calcification by 52% compared with calcification at a physiological (5 mM) glucose concentration (correlation and regression analysis: r = -0.55, p = .025 with increased concentration of glucose). Conclusions: In vitro hyperglycemia-like conditions attenuated calcification in VICs. High glucose levels may trigger a series of events that secondarily stimulate calcification of VICs in vivo.

Dystrophic calcinosis: structural and morphological composition, and evaluation of ethylenediaminetetraacetic acid ('EDTA') for potential local treatment.

BACKGROUND: To perform a detailed morphological analysis of the inorganic portion of two different clinical presentations of calcium-based deposits retrieved from subjects with SSc and identify a chemical dissolution of these deposits suitable for clinical use. METHODS: Chemical analysis using Fourier Transform IR spectroscopy ('FTIR'), Raman microscopy, Powder X-Ray Diffraction ('PXRD'), and Transmission Electron Microscopy ('TEM') was undertaken of two distinct types of calcinosis deposits: paste and stone. Calcinosis sample titration with ethylenediaminetetraacetic acid ('EDTA') assessed the concentration at which the EDTA dissolved the calcinosis deposits in vitro. RESULTS: FTIR spectra of the samples displayed peaks characteristic of hydroxyapatite, where signals attributable to the phosphate and carbonate ions were all identified. Polymorph characterization using Raman spectra were identical to a hydroxyapatite reference while the PXRD and electron diffraction patterns conclusively identified the mineral present as hydroxyapatite. TEM analysis showed differences of morphology between the samples. Rounded particles from stone samples were up to a few micron in size, while needle-like crystals from paste samples reached up to 0.5 µm in length. Calcium phosphate deposits were effectively dissolved with 3% aqueous solutions of EDTA, in vitro. Complete dissolution of both types of deposit was achieved in approximately 30 min using a molar ratio of EDTA/HAp of ≈ 300. CONCLUSIONS: Stone and paste calcium-based deposits both comprise hydroxyapatite, but the constituent crystals vary in size and morphology. Hydroxyapatite is the only crystalline polymorph present in the SSc-related calcinosis deposits. Hydroxyapatite can be dissolved in vitro using a dosage of EDTA considered safe for clinical application. Further research is required to establish the optimal medium to develop the medical product, determine the protocol for clinical application, and to assess the effectiveness of EDTA for local treatment of dystrophic calcinosis.

Exploring the Biological Overlapping Between Brain Calcifications and Tumorgenesis.

This article discusses a rare case of coexistent meningiomas and Primary familial brain calcification (PFBC). PFBC is a neurodegenerative disease characterized by brain calcifications and a variety of neuropsychiatric symptoms and signs, with pathogenic variants in specific genes. The study explores the potential link between PFBC and meningiomas, highlighting shared features like intralesional calcifications and common genes such as MEA6. The article also revisits PFBC patients developing other brain tumors, particularly gliomas, emphasizing the intersection of oncogenes like PDGFB and PDGFRB in both calcifications and tumor progression. In recent investigations, attention has extended beyond brain tumors to breast cancer metastasis, unveiling a noteworthy connection. These findings suggest a broader connection between brain calcifications and tumors, encouraging a reevaluation of therapeutic approaches for PFBC.

Fibroblasts' secretome from calcified and non-calcified dermis in Pseudoxanthoma elasticum differently contributes to elastin calcification.

Pseudoxanthoma elasticum (PXE) is a rare disease characterized by ectopic calcification, however, despite the widely spread effect of pro/anti-calcifying systemic factors associated with this genetic metabolic condition, it is not known why elastic fibers in the same patient are mainly fragmented or highly mineralized in clinically unaffected (CUS) and affected (CAS) skin, respectively. Cellular morphology and secretome are investigated in vitro in CUS and CAS fibroblasts. Here we show that, compared to CUS, CAS fibroblasts exhibit: a) differently distributed and organized focal adhesions and stress fibers; b) modified cell-matrix interactions (i.e., collagen gel retraction); c) imbalance between matrix metalloproteinases and tissue inhibitor of metalloproteinases; d) differentially expressed pro- and anti-calcifying proteoglycans and elastic-fibers associated glycoproteins. These data emphasize that in the development of pathologic mineral deposition fibroblasts play an active role altering the stability of elastic fibers and of the extracellular matrix milieu creating a local microenvironment guiding the level of matrix remodeling at an extent that may lead to degradation (in CUS) or to degradation and calcification (in CAS) of the elastic component. In conclusion, this study contributes to a better understanding of the mechanisms of the mineral deposition that can be also associated with several inherited or age-related diseases (e.g., diabetes, atherosclerosis, chronic kidney diseases).

High phosphate and calcium induce osteoblastic phenotype switching and calcification of corneal epithelial cells in a Runx2-dependent and synergistic manner; a possible mechanism of chronic kidney disease-associated corneal calcification.

Patients with advanced chronic kidney disease (CKD) have elevated circulating calcium × phosphate product levels and exhibit soft tissue calcification. Besides the cardiovascular system, calcification is commonly observed in the cornea in CKD patients on hemodialysis. Cardiovascular calcification is a cell-mediated, highly regulated process, and we hypothesized that a similar regulatory mechanism is implicated in corneal calcification with the involvement of corneal epithelial cells (CECs). We established a mouse model of CKD-associated corneal calcification by inducing CKD in DBA/2J mice with an adenine and high phosphate diet. CKD was associated with aorta and corneal calcification as detected by OsteoSense staining and corneal Ca measurement (1.67-fold elevation, p < 0.001). In vitro, excess phosphate and Ca induced human CEC calcification in a dose-dependent and synergistic manner, without any influence on cell viability. High phosphate and Ca-containing osteogenic medium (OM; 2.5 mmol/L excess phosphate and 0.6 mmol/L excess Ca over control) increased the protein expression of Runx2 and induced its nuclear translocation. OM increased the expression of the bone-specific Ca-binding protein osteocalcin (130-fold increase, p < 0.001). Silencing of Runx2 attenuated OM-induced CEC calcification. Immunohistology revealed upregulation of Runx2 and overlapping between the Runx2 and the Alizarin red positive areas of calcification in the cornea of CKD mice. This work sheds light on the mechanism of CKD-induced corneal calcification and provides tools to test calcification inhibitors for the prevention of this detrimental process.

Fusion of Platelet Derived Growth Factor Receptor Alpha (PDGFRA) With Ubiquitin Specific Peptidase 8 (USP8) in a Calcified Chondroid Mesenchymal Neoplasm Harboring t(4;15)(q12;q21) as a Sole Aberration.

BACKGROUND/AIM: The term "calcified chondroid mesenchymal neoplasm" was introduced in 2021 to describe a group of tumors characterized by various morphological features, including the formation of cartilage or chondroid matrix. These tumors frequently carry chimeric genes where the 5'-end partner gene is fibronectin 1 and the 3'-end partner gene codes for receptor tyrosine kinase. Our study explores fusion of the genes platelet-derived growth factor receptor alpha (PDGFRA) and ubiquitin-specific peptidase 8 (USP8) in calcified chondroid mesenchymal neoplasm. CASE REPORT: Genetic investigations were conducted on a tumor located in the leg of a 71-year-old woman. G-banding analysis of short-term cultured tumor cells revealed the karyotype 46,XX,t(4;15)(q12;q21)[6]/46,XX[4]. RNA sequencing detected in-frame PDGFRA::USP8 and USP8::PDGFRA chimeric transcripts, which were validated by RT-PCR/Sanger sequencing. The PDGFRA::USP8 chimeric protein is predicted to have cell membrane location and functions as a chimeric ubiquitinyl hydrolase. The USP8::PDGFRA protein was predicted to be nuclear and function as a positive regulator of cellular metabolic process. CONCLUSION: We report, for the first time, a calcified chondroid mesenchymal neoplasm carrying a balanced t(4;15)(q12;q21) chromosomal translocation, resulting in the generation of both PDGFRA::USP8 and USP8::PDGFRA chimeras. The PDGFRA::USP8 protein is located on the cell membrane and functions as a chimeric ubiquitinyl hydrolase, activated by PDGFs. Conversely, USP8::PDGFRA is a nuclear protein regulating metabolic processes.

Histological Findings in the Eyes of Abcc6 Knockout Rat Model of Pseudoxanthoma Elasticum.

Purpose: To describe the ocular findings of murine pseudoxanthoma elasticum (PXE) models with ATP-binding cassette subfamily C member 6 (Abcc6) gene knockout. Methods: This experiment was conducted in four Abcc6-/- rats and compared with six wild-type Abcc6+/+ control rats. The animals underwent necropsy at 6 months of age. Histological examination of the eyes was performed. Results: Histological examination of eight eyes from four Abcc6-/- rats revealed multiple nodular foci of calcification in the uvea, sclera, and conjunctiva, focally in perivascular distribution, as well as linear and nodular calcification of Bruch's membrane. Calcific foci were not associated with inflammation in the knockout rats. There was no evidence of calcification in control eyes. Discussion: The Abcc6-/- rat model shows that PXE can affect multiple ocular tissues beyond the calcification in Bruch's membrane noted in human eyes. Nodular calcific foci probably correspond to comet lesions seen in patients with PXE. The presence of ectopic calcium without inflammation distinguishes it from inflammatory calcium deposition in atherosclerosis. Further studies are needed to determine why PXE does not cause inflammatory infiltration. Translational Relevance: The Abcc6-/- murine model may be suitable for studying ocular PXE pathophysiology and ectopic calcification and developing effective therapies.

The interplay between crystallinity and the levels of Zn and carbonate in synthetic microcalcifications directs thyroid cell malignancy.

One of the key challenges in diagnosing thyroid cancer lies in the substantial percentage of indeterminate diagnoses of thyroid nodules that have undergone ultrasound-guided fine-needle aspiration (FNA) biopsy for cytological evaluation. This delays the definitive diagnosis and treatment plans. We recently demonstrated that hydroxyapatite microcalcifications (MCs) aspirated from thyroid nodules may aid nodule diagnosis based on their composition. In particular, Zn-enriched MCs have emerged as potential cancer biomarkers. However, a pertinent question remains: is the elevated Zn content within MCs a consequence of cancer, or do the Zn-enriched MCs encourage tumorigenesis? To address this, we treated the human thyroid cancer cell line MDA-T32 with synthetic MC analogs comprising hydroxyapatite crystals with varied pathologically relevant Zn fractions and assessed the cellular response. The MC analogs exhibited an irregular surface morphology similar to FNA MCs observed in cancerous thyroid nodules. These MC analogs displayed an inverse relationship between Zn fraction and crystallinity, as shown by X-ray diffractometry. The zeta potential of the non-Zn-bearing hydroxyapatite crystals was negative, which decreased once Zn was incorporated into the crystal. The MC analogs were not cytotoxic. The cellular response to exposure to these crystals was evaluated in terms of cell migration, proliferation, the tendency of the cells to form multicellular spheroids, and the expression of cancer markers. Our findings suggest that, if thyroid MCs play a role in promoting cancerous behavior in vivo, it is likely a result of the interplay of crystallinity with Zn and carbonate fractions in MCs.

Identification of Circulating Inflammatory Proteins Associated with Calcific Aortic Valve Stenosis by Multiplex Analysis.

Calcific aortic valve stenosis (CAVS) is characterized by increasing inflammation and progressive calcification in the aortic valve leaflets and is a major cause of death in the aging population. This study aimed to identify the inflammatory proteins involved in CAVS and provide potential therapeutic targets. We investigated the observational and causal associations of 92 inflammatory proteins, which were measured using affinity-based proteomic assays. Firstly, the case-control cohort identified differential proteins associated with the occurrence and progression of CAVS. Subsequently, we delved into exploring the causal impacts of these associated proteins through Mendelian randomization. This involved utilizing genetic instruments derived from cis-protein quantitative loci identified in genome-wide association studies, encompassing a cohort of over 400,000 individuals. Finally, we investigated the gene transcription and protein expression levels of inflammatory proteins by single-cell and immunohistochemistry analysis. Multivariate logistic regression and spearman's correlation analysis showed that five proteins showed a significant positive correlation with disease severity. Mendelian randomization showed that elevated levels of two proteins, namely, matrix metallopeptidase-1 (MMP1) and sirtuin 2 (SIRT2), were associated with an increased risk of CAVS. Immunohistochemistry and single-cell transcriptomes showed that expression levels of MMP1 and SIRT2 at the tissue and cell levels were significantly higher in calcified valves than in non-calcified control valves. These findings indicate that MMP1 and SIRT2 are causally related to CAVS and open up the possibility for identifying novel therapeutic targets.

Calcification-associated molecular traits and therapeutic strategies in hormone receptor-positive HER2-negative breast cancer.

OBJECTIVE: Mammographic calcifications are a common feature of breast cancer, but their molecular characteristics and treatment implications in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer remain unclear. METHODS: We retrospectively collected mammography records of an HR+/HER2- breast cancer cohort (n = 316) with matched clinicopathological, genomic, transcriptomic, and metabolomic data. On the basis of mammographic images, we grouped tumors by calcification status into calcification-negative tumors, tumors with probably benign calcifications, tumors with calcification of low-moderate suspicion for maligancy and tumors with calcification of high suspicion for maligancy. We then explored the molecular characteristics associated with each calcification status across multiple dimensions. RESULTS: Among the different statuses, tumors with probably benign calcifications exhibited elevated hormone receptor immunohistochemical staining scores, estrogen receptor (ER) pathway activation, lipid metabolism, and sensitivity to endocrine therapy. Tumors with calcifications of high suspicion for malignancy had relatively larger tumor sizes, elevated lymph node metastasis incidence, Ki-67 staining scores, genomic instability, cell cycle pathway activation, and may benefit from cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors. CONCLUSIONS: Our research established links between tumor calcifications and molecular features, thus proposing potential precision treatment strategies for HR+/HER2- breast cancer.

miRNA Regulation of Cell Phenotype and Parietal Remodeling in Atherosclerotic and Non-Atherosclerotic Aortic Aneurysms: Differences and Similarities.

Aortic aneurysms are a serious health concern as their rupture leads to high morbidity and mortality. Abdominal aortic aneurysms (AAAs) and thoracic aortic aneurysms (TAAs) exhibit differences and similarities in their pathophysiological and pathogenetic features. AAA is a multifactorial disease, mainly associated with atherosclerosis, characterized by a relevant inflammatory response and calcification. TAA is rarely associated with atherosclerosis and in some cases is associated with genetic mutations such as Marfan syndrome (MFS) and bicuspid aortic valve (BAV). MFS-related and non-genetic or sporadic TAA share aortic degeneration with endothelial-to-mesenchymal transition (End-Mt) and fibrosis, whereas in BAV TAA, aortic degeneration with calcification prevails. microRNA (miRNAs) contribute to the regulation of aneurysmatic aortic remodeling. miRNAs are a class of non-coding RNAs, which post-transcriptionally regulate gene expression. In this review, we report the involvement of deregulated miRNAs in the different aortic remodeling characterizing AAAs and TAAs. In AAA, miRNA deregulation appears to be involved in parietal inflammatory response, smooth muscle cell (SMC) apoptosis and aortic wall calcification. In sporadic and MFS-related TAA, miRNA deregulation promotes End-Mt, SMC myofibroblastic phenotypic switching and fibrosis with glycosaminoglycan accumulation. In BAV TAA, miRNA deregulation sustains aortic calcification. Those differences may support the development of more personalized therapeutic approaches.

Idiopathic mesenteric phlebosclerosis occurring in a patient with liver cirrhosis: A case report.

BACKGROUND: Idiopathic mesenteric phlebosclerosis (IMP) is a rare gastrointestinal disease with unclear etiology and pathogenesis. IMP occurring in a patient with liver cirrhosis is more scarcely reported than independent IMP. In this study, we reported a case of IMP occurring in a patient with liver cirrhosis, so as to provide a reference for understanding liver cirrhosis with IMP. METHOD: A 63-year-old man with liver cirrhosis was admitted in the hospital's department of infectious disease because of fatigue and constipation for 1 month. The patient had an irregular medical history of antivirus drug and Chinese herbal medicine intake because of the hepatitis B virus infection. No other abnormalities were found in the functions of the liver, coagulation, renal, or complete blood count. Fecal occult blood tests were all positive in 5 detections. Contrast-enhanced computed tomography revealed liver cirrhosis and showed thickening of the wall of the right hemicolon and multiple calcifications of the mesenteric veins. Mesenteric vein computed tomography venography displayed diffuse colon mural thickening of the right colon and tortuous linear calcification line in the right colic veins. Colonoscopy revealed a purple-blue, swollen, rough, and vanished vascular texture mucosa. He was finically diagnosed as liver cirrhosis with IMP by a series of examinations during hospitalization. RESULTS: His symptoms of fatigue and constipation subsided after conservative treatment and withdraw from Chinese herbal medicine. The patient experienced no obvious discomfort during the follow-up period. CONCLUSION: A comprehensive medical diagnosis is necessary for the discovery of IMP, especially IMP with liver cirrhosis. Liver cirrhosis maybe play a key role in the development of IMP. The regulatory mechanism of liver cirrhosis contributing to IMP needs to be further studied based on more clinical cases.

Inhibition of BMP signaling pathway induced senescence and calcification in anaplastic meningioma.

PURPOSE: Meningiomas are the most common type of brain tumors and are generally benign, but malignant atypical meningiomas and anaplastic meningiomas frequently recur with poor prognosis. The metabolism of meningiomas is little known, so few effective treatment options other than surgery and radiation are available, and the targets for treatment of recurrence are not well defined. The Aim of this paper is to find the therapeutic target. METHODS: The effects of bone morphogenetic protein (BMP) signal inhibitor (K02288) and upstream regulator Gremlin2 (GREM2) on meningioma's growth and senescence were examined. In brief, we examined as follows: 1) Proliferation assay by inhibiting BMP signaling. 2) Comprehensive analysis of forced expression GREM2.3) Correlation between GREM2 mRNA expression and proliferation marker in 87 of our clinical samples. 4) Enrichment analysis between GREM2 high/low expressed groups using RNA-seq data (42 cases) from the public database GREIN. 5) Changes in metabolites and senescence markers associated with BMP signal suppression. RESULTS: Inhibitors of BMP receptor (BMPR1A) and forced expression of GREM2 shifted tryptophan metabolism from kynurenine/quinolinic acid production to serotonin production in malignant meningiomas, reduced NAD + /NADH production, decreased gene cluster expression involved in oxidative phosphorylation, and caused decrease in ATP. Finally, malignant meningiomas underwent cellular senescence, decreased proliferation, and eventually formed psammoma bodies. Reanalyzed RNA-seq data of clinical samples obtained from GREIN showed that increased expression of GREM2 decreased the expression of genes involved in oxidative phosphorylation, similar to our experimental results. CONCLUSIONS: The GREM2-BMPR1A-tryptophan metabolic pathway in meningiomas is a potential new therapeutic target.

Heterotopic bone formation in a case of clear cell renal cell carcinoma: A case report.

Renal cell carcinoma (RCC) with heterotopic formation has been reported very rarely. We report this rare entity in a 33-year-old female patient who came to the out-patient department after complaining of pain in the lumbar region of the left side for 2 years. A computed tomography scan showed a heterogeneously enhancing lesion originating from the posterior cortex of the left kidney in the upper pole. It had many chunky calcification foci and was treated with left robotic partial nephrectomy. Histo-pathological examination revealed clear cell RCC with the heterotopic bone formation with a tumor size measuring 5 × 4 × 2.5 cm; the tumor was limited to the kidney, and the tumor resection margin were free of tumor, WHO/ISUP Grade 2. The pathological stage (AJCC 8th edition PTNM) was p T1b p NX p MX. The prognostic implications regarding calcification are poorly addressed in the literature. Patients suffering from osseous metaplasia are often in their early stages of the disease and have a favorable prognosis.

Metastatic neuroendocrine carcinoma: Liver metastases presenting with diffuse nodular calcifications on CT.

We report a case of the 46-year-old female patient, who presented with diffuse nodular liver calcifications on computed tomography. Histopathology of the calcified nodules revealed neuroendocrine tumors (NETs). Calcified NET liver metastases are extremely rare and need to be considered in the differential diagnosis with other benign and malignant liver calcification.

Calcification patterns and morphology of Sella turcica are related to anteroposterior skeletal malocclusions: A cross-sectional study.

BACKGROUND: The sphenoid bone is an irregular, unpaired, symmetrical bone located in the middle of the anterior skull and is involved in craniofacial growth and development. Since the morphology of Sella turcica (ST) is associated with different craniofacial patterns, this study aimed to investigate if there is a correlation between ST morphology on the one hand and sagittal craniofacial patterns on the other hand. METHODS: This study was conducted with a convenience sample that included Brazilian individuals undergoing orthodontic treatment. Lateral cephalograms were used to evaluate the calcification pattern and morphology of ST, as well as skeletal class by analyzing the ANB angle. Pearson's chi-square test with Bonferroni post-hoc test was performed to evaluate the association between ST calcification pattern and morphology, and anteroposterior skeletal malocclusion. The established significance level was 0.05. RESULTS: The study collective was comprised of 305 orthodontic patients (178 (58.4 %) female, 127 (41.6 %) male), who had a mean age of 23.2 (±10.6) years. 131 participants (42.9 %) presented skeletal class I, 142 (46.6%) skeletal Class II, and 32 (10.5%) had a skeletal class III. The degree of prognathism of the mandible showed a homogenous distribution within the study collective (91 (29.9 %) orthognathic, 100 (32.9 %) retrognathic, 113 (37.2 %) prognathic mandible). Concerning the maxilla, 92 (30.2%) individuals presented an orthognathic upper jaw, whereas 60 (19.7%) showed maxillary retrognathism and 153 (50.2%) maxillary prognathism. Compared to patients with skeletal class I, skeletal class III individuals presented significantly more hypertrophic posterior clinoid process (p<0.007) and pyramidal shape of the dorsum of the ST (p<0.038). CONCLUSIONS: Our results suggest that the hypertrophic posterior clinoid process and pyramidal shape of the ST dorsum are more prevalent in individuals with skeletal class III malocclusion.

Lethal hemopericardium caused by infection of mitral annular calcification: An autopsy case report.

Mitral annular calcification (MAC) is a chronic and degenerative condition involving calcification of the mitral annulus. MAC is a risk factor for coronary artery disease, cardiovascular events, stroke, and cardiovascular death. However, patients with MAC are often asymptomatic. Herein, we present the first case of cardiac tamponade due to infection of MAC in forensic pathology. An 80-year-old woman was found in cardiopulmonary arrest shortly after experiencing fatigue. She was transferred to a hospital, and despite chest compression and ventilation, she was pronounced dead due to no response. Postmortem computed tomography, autopsy, and histological examination showed MAC, abscess formation involving Gram-positive cocci on the MAC, and fistulation of the abscess into the intracardial pericardial cavities, resulting in a massive lethal hemopericardium.

A Comprehensive Study of Meningioma Biomineralization: Morphological, Crystallographic, and Immunohistochemical Aspects.

Biomineralization of brain tissues occurs both in normal and pathological conditions. Dura mater biomineralization is widespread and occurs in 1-72% of cases, depending on the patient's age and research method. The amount of biomineral deposits under the conditions of tumor growth in the meninges only increases, reaching 100% in the case of psammomatous meningiomas. Since calcifications are often found in the meninges, the problem of differential diagnosis with calcified meningiomas arises. A total of 30 samples of meningiomas with signs of biomineralization-dense structure, characteristic crunch, psammoma bodies (group I) and 30 samples of meningiomas without any signs of biomineralization were examined as controls (group II). To detect pathological biomineralization, the meningioma tissue was studied using the methods of macroscopic description, histology, histochemistry, and immunohistochemistry, scanning electron microscopy with microanalysis, and transmission electron microscopy. A significantly higher level of caspase3 and features of the expression of osteoblastic markers (a lower level of OPG expression and a higher level of the presence of RANKL in group I, the absence of fluctuations in the expression of SPARC) may indicate a dystrophic type of development of biomineral deposits in meningiomas.