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.

Identification novel mutations and phenotypic spectrum expanding in PATL2 in infertile women with IVF/ICSI failure.

AIM: Abnormalities in oocyte maturation, fertilization, and early embryonic development are major causes of primary infertility in women who are undergoing IVF/ICSI attempts. Although many genetic factors responsible for these abnormal phenotypes have been identified, there are more additional pathogenic genes and variants yet to be discovered. Previous studies confirmed that bi-allelic PATL2 deficiency is an important factor for female infertility. In this study, 935 infertile patients with IVF/ICSI failure were selected for whole-exome sequencing, and 18 probands carrying PATL2 variants with a recessive inheritance pattern were identified. METHODS: We estimated that the prevalence contributed by PATL2 was 1.93% (18/935) in our study cohort. RESULTS: 15 novel variants were found in those families, including c.1093C > T, c.1609dupA, c.1204C > T, c.643dupG, c.877-2A > G, c.1228C > G, c.925G > A, c.958G > A, c.4A > G, c.1258T > C, c.1337G > A, c.1264dupA, c.88G > T, c.1065-2A > G, and c.1271T > C. The amino acids altered by the corresponding variants were highly conserved in mammals, and in silico analysis and 3D molecular modeling suggested that the PATL2 mutants impaired the physiologic function of the resulting proteins. Diverse clinical phenotypes, including oocyte maturation defect, fertilization failure, and early embryonic arrest might result from different variants of PATL2. CONCLUSIONS: These results expand the spectrum of PATL2 variants and provide an important reference for genetic counseling for female infertility, and they increase our understanding of the mechanisms of oocyte maturation arrest caused by PATL2 deficiency.

Characteristics of microplastics in the atmosphere of Anyang City.

In order to clarify the characteristics of microplastics in the atmosphere of Anyang city, TSP, PM10, and PM2.5 samples are collected when the ambient air quality is good, slightly polluted, and severely polluted. After pretreatment, the physical and chemical characteristics are observed and identified by using stereomicroscope and micro-infrared spectrometer. The results show that the average abundance of microplastics is 0.19 items/m3, 0.26 items/m3, and 0.42 items/m3, respectively, when the ambient air quality is good, light pollution, and heavy pollution in Anyang City. It can be seen that with the decline of ambient air quality, the average abundance of microplastics in TSP, PM2.5, and PM10 gradually increases. The black fiber strip microplastics account for about 80% of the total TSP, PM2.5, and PM10 in the ambient air of Anyang City, followed by yellow flake and black granular microplastics and a small amount of green, red, and blue fiber strip microplastics. AQI has a good correlation with the abundance of microplastics in TSP, PM10, and PM2.5, and the maximum microplastic trapping effect could be obtained according to the sampling method of PM2.5 in the ambient air. The main components of microplastics are cellophane, followed by PET and EVA. The explorations of human respiratory exposure risk assessment show that with the increase of AQI, the daily intake of microplastics in adults also increased. At high levels of pollution, the human body breathes an average of 222 ± 5 microplastics per day.

Magnesium decreases urine supersaturation but not calcium oxalate stone formation in genetic hypercalciuric stone-forming rats.

BACKGROUND/AIMS: Hypercalciuria is the most common identifiable risk factor predisposing to CaOx stone formation. Increased oral magnesium intake may lead to decreased CaOx stone formation by binding intestinal Ox leading to decreased absorption and/or binding urinary Ox to decrease urinary supersaturation. This study assessed the effect of oral magnesium on 24-hour urine ion excretion, supersaturation, and kidney stone formation in a genetic hypercalciuric stone-forming (GHS) rat model of human idiopathic hypercalciuria. METHODS: When fed the oxalate precursor, hydroxyproline, every GHS rat develops CaOx stones. The GHS rats were fed a normal calcium and phosphorus diet with hydroxyproline to induce CaOx , were divided into three groups of ten rats per group: control diet with 4.0 g/kg MgO, low MgO diet (0.5 g/kg), and high MgO diet (8 g/kg). At 6 weeks, twenty-four-hour urines were collected, and urine chemistry and supersaturation were determined. Stone formation was quantified. RESULTS: The GHS rats fed the low and high Mg diets had a significant reduction and increase, respectively, in urinary Mg compared to those fed the control diet. Dietary Mg did not alter urine Ca excretion while the low Mg diet led to a significant fall in urinary Ox. Urine supersaturation with respect to CaOx was significantly increased with low Mg, whereas urine supersaturation was significantly decreased with high Mg. There was no effect of dietary Mg on stone formation within 6 weeks of treatment. CONCLUSION: Dietary magnesium decreases urine supersaturation but not CaOx stone formation in GHS rats.

Bi-allelic missense variants in MEI4 cause preimplantation embryonic arrest and female infertility.

Preimplantation embryonic arrest is an important pathogenesis of female infertility, but little is known about the genetic factors behind this phenotype. MEI4 is an essential protein for DNA double-strand break formation during meiosis, and Mei4 knock-out female mice are viable but sterile, indicating that MEI4 plays a crucial role in reproduction. To date, MEI4 has not been found to be associated with any human reproductive diseases. Here, we identified six compound heterozygous and homozygous MEI4 variants-namely, c.293C > T, p.(Ser98Leu), c.401C > G, p.(Pro134Arg), c.391C > G, p.(Pro131Ala), c.914A > T, p.(Tyr305Phe), c.908C > G, p.(Ala303Gly), and c.899A > T, p.(Gln300Leu)-in four independent families that were responsible for female infertility mainly characterized by preimplantation embryonic arrest. In vitro, we found that these variants reduced the interaction between MEI4 and DNA. In vivo, we generated a knock-in mouse model and demonstrated that female mice were infertile and were characterized by developmental defects during oogenesis. Our findings reveal the important roles of MEI4 in human reproduction and provide a new diagnostic marker for genetic counseling of clinical infertility patients.

Effects of Temperature on Novel Molecular Perovskite Energetic Material (C6H14N2)[NH4(ClO4)3]: A Molecular Dynamics Simulation.

Molecular dynamics (MD) simulations were performed on the energetic molecular perovskite (C6H14N2)[NH4(ClO4)3], with excellent detonation properties, thermal stability, and high specific impulse, which is a potential replacement for AP as the next generation propellants. The cohesive energy density, binding energy, pair correlation function, maximum bond length (Lmax) of the N-H trigger bond, and mechanical properties of the (C6H14N2)[NH4(ClO4)3] were reported. The calculated cohesive energy density and binding energy decrease with increasing temperature, indicating a gradual decrease in the thermal stability with temperature. In addition, H···O hydrogen bonding interactions have been found based on the results of pairwise correlation functions. The maximum length (Lmax) of the N-H trigger bond was calculated and used as a criterion to theoretically judge the impact sensitivity. The maximum bond length of the N-H trigger bond grows gradually with temperature; however, it does very slightly yet gradually above 373 K. This suggests that an increase in temperature leads to a higher impact sensitivity and lower thermal stability. However, this effect becomes less pronounced when the temperature surpasses 373 K. Moreover, the calculated mechanical data indicate that as the temperature rises, the material's stiffness, hardness, yield strength, and fracture strength all decrease. The material's ductility shows an upward trend with increasing temperature, reaching its peak at 373 K and subsequently declining as the temperature continues to rise.

Novel Treatments for PXE: Targeting the Systemic and Local Drivers of Ectopic Calcification.

Pseudoxanthoma elasticum (PXE) is a heritable multisystem ectopic calcification disorder. The gene responsible for PXE, ABCC6, encodes ABCC6, a hepatic efflux transporter regulating extracellular inorganic pyrophosphate (PPi), a potent endogenous calcification inhibitor. Recent studies demonstrated that in addition to the deficiency of plasma PPi, the activated DDR/PARP signaling in calcified tissues provides an additional possible mechanism of ectopic calcification in PXE. This study examined the effects of etidronate (ETD), a stable PPi analog, and its combination with minocycline (Mino), a potent inhibitor of DDR/PARP, on ectopic calcification in an Abcc6-/- mouse model of PXE. Abcc6-/- mice, at 4 weeks of age, before the development of ectopic calcification, were treated with ETD, Mino, or both for 18 weeks. Micro-computed tomography, histopathologic examination, and quantification of the calcium content in Abcc6-/- mice treated with both ETD and Mino revealed further reduced calcification than either treatment alone. The effects were associated with reduced serum alkaline phosphatase activity without changes in plasma PPi concentrations. These results suggest that ETD and Mino combination therapy might provide an effective therapeutic approach for PXE, a currently intractable disease.

Estimation and mapping of soil texture content based on unmanned aerial vehicle hyperspectral imaging.

Soil texture is one of the important physical and natural properties of soil. Much of the current research focuses on soil texture monitoring using non-imaging geophysical spectrometers. However there are fewer studies utilizing unmanned aerial vehicle (UAV) hyperspectral data for soil texture monitoring. UAV mounted hyperspectral cameras can be used for quickly and accurately obtaining high-resolution spatial information of soil texture. A foundation has been laid for the realization of rapid soil texture surveys using unmanned airborne hyperspectral data without field sampling. This study selected three typical farmland areas in Huangshui Basin of Qinghai as the study area, and a total of 296 soil samples were collected. Data calibration of UAV spectra using laboratory spectra and field in situ spectra to explore the feasibility of applying laboratory soil texture models directly to field conditions. This results show that UAV hyperspectral imagery combined with machine learning can obtain a set of ideal processing methods. The pre-processing of the spectral data can obtain high accuracy of soil texture estimation and good mapping effect. The results of this study can provide effective technical support and decision-making assistance for future agricultural land planning on the Tibetan Plateau. The main innovation of this study is to establish a set of processing procedures and methods applicable to UAV hyperspectral imagery to provide data reference for monitoring soil texture in agricultural fields on the Tibetan Plateau.

Interaction, Insensitivity and Thermal Conductivity of CL-20/TNT-Based Polymer-Bonded Explosives through Molecular Dynamics Simulation.

Binders mixed with explosives to form polymer-bonded explosives (PBXs) can reduce the sensitivity of the base explosive by improving interfacial interactions. The interface formed between the binder and matrix explosive also affects the thermal conductivity. Low thermal conductivity may result in localized heat concentration inside the PBXs, causing the detonation of the explosive. To investigate the binder-explosive interfacial interactions and thermal conductivity, PBXs with polyurethane as the binder and 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane/2,4,6-trinitrotoluene (CL-20/TNT) co-crystal as the matrix explosive were investigated through molecular dynamics (MD) simulations and reverse non-equilibrium molecular dynamics (rNEMD) simulation. The analysis of the pair correlation function revealed that there are hydrogen bonding interactions between Estane5703 and CL-20/TNT. The length of the trigger bonds was adopted as a theoretical criterion of sensitivity, and the effect of polymer binders on the sensibility of PBXs was correlated by analyzing the interfacial trigger bonds and internal trigger bonds of PBXs for the first time. The results indicated that the decrease in sensitivity of CL-20/TNT mainly comes from the CL-20/TNT contact with Estane5703. Therefore, the sensitivity of CL-20/TNT-based PBXs can be further reduced by increasing the contact area between CL-20/TNT and Estane5703. The thermal conductivity of PBXs composed of Estane5703 and CL-20/TNT (0 0 1), (0 1 0) and (1 0 0) crystal planes, respectively, were calculated through rNEMD simulations, and the results showed that only the addition of Estane5703 to the (1 0 0) crystal plane can improve the thermal conductivity of PBX100.

High Expression of Microtubule-associated Protein TBCB Predicts Adverse Outcome and Immunosuppression in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a devastating blood cancer with high heterogeneity and ill-fated outcome. Despite numerous advances in AML treatment, the prognosis remains poor for a significant proportion of patients. Consequently, it is necessary to accurately and comprehensively identify biomarkers as soon as possible to enhance the efficacy of diagnosis, prognosis and treatment of AML. In this study, we aimed to identify prognostic markers of AML by analyzing the cohorts from TCGA-LAML database and GEO microarray datasets. Interestingly, the transcriptional level of microtubule-associated protein TBCB in AML patients was noticeably increased when compared with normal individuals, and this was verified in two independent cohorts (GSE9476 and GSE13159) and with our AML patients. Furthermore, univariate and multivariate regression analysis revealed that high TBCB expression was an independent poor prognostic factor for AML. GO and GSEA enrichment analysis hinted that immune-related signaling pathways were enriched in up-regulated DEGs between two populations separated by the median expression level of TBCB. By constructing a protein-protein interaction network, we obtained six hub genes, all of which are immune-related molecules, and their expression levels were positively linked to that of TBCB. In addition, the high expression of three hub genes was significantly associated with a poor prognosis in AML. Moreover, we found that the tumor microenvironment in AML with high TBCB expression tended to be infiltrated by NK cells, especially CD56bright NK cells. The transcriptional levels of NK cell inhibitory receptors and their ligands were positively related to that of TBCB, and their high expression levels also predicted poor prognosis in AML. Notably, we found that the down-regulation of TBCB suppressed cell proliferation in AML cell lines by enhancing the apoptosis and cell cycle arrest. Finally, drug sensitivity prediction illustrated that cells with high TBCB expression were more responsive to ATRA and midostaurin but resistant to cytarabine, dasatinib, and imatinib. In conclusion, our findings shed light on the feasibility of TBCB as a potential predictor of poor outcome and to be an alternative target of treatment in AML.

Risk Factors and Countermeasures of Stress Urinary Incontinence after Mesh Implantation for Patients with Pelvic Organ Prolapse.

OBJECTIVES: We aimed to explore the risk factors and countermeasures of stress urinary incontinence (SUI) after mesh implantation for patients with pelvic organ prolapse (POP). METHODS: A total of 224 POP patients undergoing mesh implantation from January 2018 to December 2021 were divided into group A (n = 68, postoperative new-onset SUI) and group B (n = 156, without postoperative new-onset SUI). Their clinical data were collected, and the treatment outcomes were analyzed. The independent risk factors for postoperative new-onset SUI were determined through multivariate logistic regression analysis. A risk-scoring model was established and assessed. The patients with postoperative new-onset SUI were divided into low-, moderate- and high-risk groups using this model. RESULTS: Mesh implantation significantly improved the pelvic floor muscle strength and function of patients. Multivariate logistic regression analysis revealed that age ≥50 years old, gravidity ≥3 times, parity ≥3 times, history of macrosomia delivery, history of chronic respiratory diseases, vaginal delivery, and perineal laceration were independent risk factors for postoperative new-onset SUI, and pelvic floor muscle training by biofeedback electrical stimulation was a protective factor (p < 0.05). The risk-scoring model was safe, reliable and practical, with high discrimination, accuracy and efficiency. CONCLUSIONS: Age ≥50 years old, gravidity ≥3 times, parity ≥3 times, history of macrosomia delivery, history of chronic respiratory diseases, vaginal delivery, and perineal laceration are independent risk factors for postoperative new-onset SUI, and pelvic floor muscle training by biofeedback electrical stimulation is a protective factor. Therefore, POP patients with new-onset SUI following mesh implantation should receive more pelvic floor muscle training.

Artificial intelligence in thyroid ultrasound.

Artificial intelligence (AI), particularly deep learning (DL) algorithms, has demonstrated remarkable progress in image-recognition tasks, enabling the automatic quantitative assessment of complex medical images with increased accuracy and efficiency. AI is widely used and is becoming increasingly popular in the field of ultrasound. The rising incidence of thyroid cancer and the workload of physicians have driven the need to utilize AI to efficiently process thyroid ultrasound images. Therefore, leveraging AI in thyroid cancer ultrasound screening and diagnosis cannot only help radiologists achieve more accurate and efficient imaging diagnosis but also reduce their workload. In this paper, we aim to present a comprehensive overview of the technical knowledge of AI with a focus on traditional machine learning (ML) algorithms and DL algorithms. We will also discuss their clinical applications in the ultrasound imaging of thyroid diseases, particularly in differentiating between benign and malignant nodules and predicting cervical lymph node metastasis in thyroid cancer. Finally, we will conclude that AI technology holds great promise for improving the accuracy of thyroid disease ultrasound diagnosis and discuss the potential prospects of AI in this field.

A novel homozygous variant in ZFP36L2 cause female infertility due to oocyte maturation defect.

Normal oocyte maturation is an important requirement for the success of human reproduction, and defects in this process will lead to female infertility and repeated IVF/ICSI failures. In order to identify genetic factors that are responsible for oocyte maturation defect, we used whole exome sequencing in the affected individual with oocyte maturation defect from a consanguineous family and identified a homozygous variant c.853_861del (p.285_287del) in ZFP36L2. ZFP36L2 is a RNA-binding protein, which regulates maternal mRNA decay and oocyte maturation. In vitro studies showed that the variant caused decreased protein levels of ZFP36L2 in oocytes due to mRNA instability and might lead to the loss of its function to degrade maternal mRNAs. Previous study showed that the pathogenic variants in ZFP36L2 were associated with early embryonic arrest. In contrast, we identified a novel ZFP36L2 variant in the affected individual with oocyte maturation defect, which further broadened the mutational and phenotypic spectrum of ZFP36L2, suggesting that ZFP36L2 might be a genetic diagnostic marker for the affected individuals with oocyte maturation defect.

Risk Factors and Countermeasures of Stress Urinary Incontinence after Mesh Implantation for Patients with Pelvic Organ Prolapse

Abstract Objectives: We aimed to explore the risk factors and countermeasures of stress urinary incontinence (SUI) after mesh implantation for patients with pelvic organ prolapse (POP). Methods: A total of 224 POP patients undergoing mesh implantation from January 2018 to December 2021 were divided into group A (n = 68, postoperative new-onset SUI) and group B (n = 156, without postoperative new-onset SUI). Their clinical data were collected, and the treatment outcomes were analyzed. The independent risk factors for postoperative new-onset SUI were determined through multivariate logistic regression analysis. A risk-scoring model was established and assessed. The patients with postoperative new-onset SUI were divided into low-, moderate- and high-risk groups using this model. Results: Mesh implantation significantly improved the pelvic floor muscle strength and function of patients. Multivariate logistic regression analysis revealed that age ≥50 years old, gravidity ≥3 times, parity ≥3 times, history of macrosomia delivery, history of chronic respiratory diseases, vaginal delivery, and perineal laceration were independent risk factors for postoperative new-onset SUI, and pelvic floor muscle training by biofeedback electrical stimulation was a protective factor (p < 0.05). The risk-scoring model was safe, reliable and practical, with high discrimination, accuracy and efficiency. Conclusions: Age ≥50 years old, gravidity ≥3 times, parity ≥3 times, history of macrosomia delivery, history of chronic respiratory diseases, vaginal delivery, and perineal laceration are independent risk factors for postoperative new-onset SUI, and pelvic floor muscle training by biofeedback electrical stimulation is a protective factor. Therefore, POP patients with new-onset SUI following mesh implantation should receive more pelvic floor muscle training (AU)

Large-scale analysis of de novo mutations identifies risk genes for female infertility characterized by oocyte and early embryo defects.

BACKGROUND: Oocyte maturation arrest and early embryonic arrest are important reproductive phenotypes resulting in female infertility and cause the recurrent failure of assisted reproductive technology (ART). However, the genetic etiologies of these female infertility-related phenotypes are poorly understood. Previous studies have mainly focused on inherited mutations based on large pedigrees or consanguineous patients. However, the role of de novo mutations (DNMs) in these phenotypes remains to be elucidated. RESULTS: To decipher the role of DNMs in ART failure and female infertility with oocyte and embryo defects, we explore the landscape of DNMs in 473 infertile parent-child trios and identify a set of 481 confident DNMs distributed in 474 genes. Gene ontology analysis reveals that the identified genes with DNMs are enriched in signaling pathways associated with female reproductive processes such as meiosis, embryonic development, and reproductive structure development. We perform functional assays on the effects of DNMs in a representative gene Tubulin Alpha 4a (TUBA4A), which shows the most significant enrichment of DNMs in the infertile parent-child trios. DNMs in TUBA4A disrupt the normal assembly of the microtubule network in HeLa cells, and microinjection of DNM TUBA4A cRNAs causes abnormalities in mouse oocyte maturation or embryo development, suggesting the pathogenic role of these DNMs in TUBA4A. CONCLUSIONS: Our findings suggest novel genetic insights that DNMs contribute to female infertility with oocyte and embryo defects. This study also provides potential genetic markers and facilitates the genetic diagnosis of recurrent ART failure and female infertility.

Bi-allelic pathogenic variants in PABPC1L cause oocyte maturation arrest and female infertility.

Oocyte maturation arrest is one of the important causes of female infertility, but the genetic factors remain largely unknown. PABPC1L, a predominant poly(A)-binding protein in Xenopus, mouse, and human oocytes and early embryos prior to zygotic genome activation, plays a key role in translational activation of maternal mRNAs. Here, we identified compound heterozygous and homozygous variants in PABPC1L that are responsible for female infertility mainly characterized by oocyte maturation arrest in five individuals. In vitro studies demonstrated that these variants resulted in truncated proteins, reduced protein abundance, altered cytoplasmic localization, and reduced mRNA translational activation by affecting the binding of PABPC1L to mRNA. In vivo, three strains of Pabpc1l knock-in (KI) female mice were infertile. RNA-sequencing analysis showed abnormal activation of the Mos-MAPK pathway in the zygotes of KI mice. Finally, we activated this pathway in mouse zygotes by injecting human MOS mRNA, and this mimicked the phenotype of KI mice. Our findings reveal the important roles of PABPC1L in human oocyte maturation and add a genetic potential candidate gene to be screened for causes of infertility.

Corrigendum: Association between diagnostic efficacy of acoustic radiation force impulse for benign and malignant thyroid nodules and the presence or absence of non-papillary thyroid cancer: A meta-analysis.

[This corrects the article DOI: 10.3389/fonc.2023.1007464.].

ADGB variants cause asthenozoospermia and male infertility.

Asthenozoospermia is one of the main factors leading to male infertility, but the genetic mechanisms have not been fully elucidated. Variants in the androglobin (ADGB) gene were identified in an infertile male characterized by asthenozoospermia. The variants disrupted the binding of ADGB to calmodulin. Adgb-/- male mice were infertile due to reduced sperm concentration (< 1 × 106 /mL) and motility. Spermatogenesis was also abnormal, with malformation of both elongating and elongated spermatids, and there was an approximately twofold increase in apoptotic cells in the cauda epididymis. These exacerbated the decline in sperm motility. It is surprising that ICSI with testicular spermatids allows fertilization and eventually develops into blastocyst. Through mass spectrometry, we identified 42 candidate proteins that are involved in sperm assembly, flagella formation, and sperm motility interacting with ADGB. In particular, CFAP69 and SPEF2 were confirmed to bind to ADGB. Collectively, our study suggests the potential important role of ADGB in human fertility, revealing its relevance to spermatogenesis and infertility. This expands our knowledge of the genetic causes of asthenozoospermia and provides a theoretical basis for using ADGB as an underlying genetic marker for infertile males.

Weighing the Evidence for the Roles of Plasma Versus Local Pyrophosphate in Ectopic Calcification Disorders.

Ectopic calcification is characterized by inappropriate deposition of calcium mineral in nonskeletal connective tissues and can cause significant morbidity and mortality, particularly when it affects the cardiovascular system. Identification of the metabolic and genetic determinants of ectopic calcification could help distinguish individuals at the greatest risk of developing these pathological calcifications and could guide development of medical interventions. Inorganic pyrophosphate (PPi ) has long been recognized as the most potent endogenous inhibitor of biomineralization. It has been intensively studied as both a marker and a potential therapeutic for ectopic calcification. Decreased extracellular concentrations of PPi have been proposed to be a unifying pathophysiological mechanism for disorders of ectopic calcification, both genetic and acquired. However, are reduced plasma concentrations of PPi a reliable predictor of ectopic calcification? This perspective article evaluates the literature in favor and against a pathophysiological role of plasma versus tissue PPi dysregulation as a determinant of, and as a biomarker for, ectopic calcification. © 2023 American Society for Bone and Mineral Research (ASBMR).

Association between diagnostic efficacy of acoustic radiation force impulse for benign and malignant thyroid nodules and the presence or absence of non-papillary thyroid cancer: A meta-analysis.

Purpose: The aim of this study was to investigate the diagnostic efficacy of Acoustic Radiation Force Impulse (ARFI) for benign and malignant thyroid nodules in the presence and absence of non-papillary thyroid cancer (NPTC) and to determine the cut-off values of Shear Wave Velocity (SWV) for the highest diagnostic efficacy of Virtual Touch Quantification (VTQ) and Virtual Touch Tissue Imaging and Quantification (VTIQ). Methods: The diagnostic accuracy of ARFI for benign and malignant thyroid nodules was assessed by pooling sensitivity, specificity and area under the curve (AUC) in each group in the presence and absence of both non-papillary thyroid glands, using histology and cytology as the gold standard. All included studies were divided into two groups according to VTQ and VTIQ, and each group was ranked according to the magnitude of the SWV cutoff value to determine the SWV cutoff interval with the highest diagnostic efficacy for VTQ and VTIQ. Results: A total of 57 studies were collected on the evaluation of ARFI for the diagnosis of benign and malignant thyroid nodules. The results showed that the presence of non-papillary thyroid carcinoma led to differences in the specificity of VTIQ for the identification of benign and malignant thyroid nodules, and the differences were statistically significant. In addition, the diagnostic efficacy of VTQ was best when the cutoff value of SWV was in the interval of 2.48-2.55 m/s, and the diagnostic efficacy of VTIQ was best when the cutoff value of SWV was in the interval of 3.01-3.15 m/s. Conclusion: VTQ and VTIQ have a high diagnostic value for benign and malignant thyroid nodules; however, when the malignant nodules in the study contain non-papillary thyroid carcinoma occupying the thyroid gland, the findings should be viewed in a comprehensive manner.