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The cause of chronic liver diseases (CLD) remains undiagnosed in up to 30% of adult patients. Whole-Exome Sequencing (WES) could improve the diagnostic rate of genetic conditions, but it is not yet widely clinically available, due to the costs and the difficulties in results interpretation. Targeted panel sequencing (TS) represents an alternative more focused diagnostic approach. To validate a customized TS for hereditary CLD diagnosis. We designed a customized panel including 82 CLD-associated genes (iron overload, lipid metabolism, cholestatic diseases, storage diseases, specific hereditary CLD). DNA samples from 19 unrelated adult patients with undiagnosed CLD were analyzed with both TS (HaloPlex) and WES (SureSelect Human All Exon kit v5) and the performances were compared. The mean depth of the target regions obtained with TS was higher than WES (300X vs 102X). Moreover, TS yielded higher average coverage per gene and lower fraction of exons with low coverage. Overall, 374 unique variants were identified across all samples, 100 of which were "Pathogenic" or "Likely Pathogenic" variants with a high functional impact (HFI). The majority of HFI variants (80%) were detected by both methods; 14 were uniquely identified by TS and 6 by WES. Discrepancies in variant calling were mainly due to variability in read depth and insufficient coverage in the corresponding target regions. All variants were confirmed by Sanger sequencing except two uniquely detected by TS. Detection rate of TS was 94% while that of WES was 88%. TS was confirmed to be a valid first-tier genetic test, less laborious and with a detection rate comparable to or higher than WES, useful to support clinical and instrumental evaluation for hereditary CLD diagnosis. [ABSTRACT FROM AUTHOR]

Background: The cause of chronic liver diseases (CLD) remains undiagnosed in up to 30% of adult patients. Whole-Exome Sequencing (WES) can improve the diagnostic rate of genetic conditions, but it is not yet widely available, due to the costs and the difficulties in results interpretation. Targeted panel sequencing (TS) represents an alternative more focused diagnostic approach. Aims: To validate a customized TS for hereditary CLD diagnosis. Methods: We designed a customized panel including 82 CLD-associated genes (iron overload, lipid metabolism, cholestatic diseases, storage diseases, specific hereditary CLD and susceptibility to liver diseases). DNA samples from 19 unrelated adult patients with undiagnosed CLD were analyzed by both TS (HaloPlex) and WES (SureSelect Human All Exon kit v5) and the diagnostic performances were compared. Results: The mean depth of coverage of TS-targeted regions was higher with TS than WES (300x vs. 102x; p < 0.0001). Moreover, TS yielded a higher average coverage per gene and lower fraction of exons with low coverage ( p < 0.0001). Overall, 374 unique variants were identified across all samples, 98 of which were classified as "Pathogenic" or "Likely Pathogenic" with a high functional impact (HFI). The majority of HFI variants (91%) were detected by both methods; 6 were uniquely identified by TS and 3 by WES. Discrepancies in variant calling were mainly due to variability in read depth and insufficient coverage in the corresponding target regions. All variants were confirmed by Sanger sequencing except two uniquely detected by TS. Detection rate and specificity for variants in TS-targeted regions of TS were 96.9% and 97.9% respectively, whereas those of WES were 95.8% and 100%, respectively. Conclusion: TS was confirmed to be a valid first-tier genetic test, with an average mean depth per gene higher than WES and a comparable detection rate and specificity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ronzoni, Marini, Passignani, Malvestiti, Marchelli, Bianco, Pelusi, Prati and Valenti.)

Two-dimensional colloidal halide perovskite nanocrystals are promising materials for light-emitting applications. Recent studies have focused on nanoplatelets that are able to self-assemble and transform on solid substrates. However, the mechanism behind the process and the atomic arrangement of their assemblies remain unclear. Here, we present a detailed analysis of the transformation of self-assembled stacks of CsPbBr 3 nanoplatelets in solution over a period of a few months by using ex situ transmission electron microscopy and surface analysis. We demonstrate that the transformation mechanism can be understood as oriented attachment, proceeding through the following steps: (i) desorption of the ligands from the surfaces of the particles, causing the seamless atomic merging of nanoplatelet stacks into nanobelts; (ii) merging of neighboring nanobelts that form more extended nanoplates; and (iii) attachment of nanobelts and nanoplates, forming objects with an atomic structure that resembles a mosaic made of broken nanotiles. We reveal that aged nanobelts and nanoplates, which are mainly stabilized by amine/ammonium ions, link through a bilayer of CsBr, with the atomic columns of neighboring perovskite lattices shifted by a half-unit-cell, forming Ruddlesden-Popper planar faults. We also show, via in situ monitoring of the nanocrystal photoluminescence combined with transmission electron microscopy analysis, that the transformation is temperature driven and that it can take place within tens of minutes in solution and in spin-coated films. Understanding this process gives crucial information for the design and fabrication of perovskite materials, where control over the type and density of defects is desired, stimulating the development of perovskite nanocrystal structures with tailored electronic properties.

The importance of childhood and adolescence for bone development and mineral accrual is increasingly accepted, leading to a need of suitable methods for monitoring bone health even in pediatric setting. Among the several different imaging methods available for clinical measurement of bone mineral density (BMD) in children, dual-energy X-ray absorptiometry (DXA) is the most widely available and commonly used due to its reproducibility, negligible radiation dose and reliable pediatric reference data. Nevertheless, DXA in children has some technical specific features that should be known by those physicians who interpret and report this examination. We provide recommendations for optimal DXA scan reporting in pediatric setting, including indications, skeletal sites to be examined, parameters to be measured, timing of follow-up BMD measurements. Adequate report and analysis of DXA examinations are essential to prevent over- and underdiagnosis of bone mineral impairment in pediatric patients. In conclusion, a complete and exhaustive DXA report in children and adolescents is mandatory for an accurate diagnosis and a precise monitoring of pediatric bone status., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: Our aim was to estimate the in vivo reproducibility of bone mineral density (BMD) at dual-energy X-ray absorptiometry (DXA) and to compare fast array, array, and high-definition scan modes., Materials and Methods: A total of 378 patients (38 males and 340 females; mean age 63 ± 9 years) underwent DXA using a QDR-Discovery A densitometer (Hologic). Considering the three scan modes on lumbar spine and right femur, six independent groups of 30 patients were examined twice (for a total of 180 patients). Least significant change (LSC) and smallest detectable difference (SDD) were calculated. The remaining 198 patients underwent three scans of the lumbar spine (n = 92) or of the right femur (n = 106), one for each scan mode. The student t test and Bland-Altman analysis used were. Scan times were recorded and radiation dose was estimated using the ICRP60 method., Results: Intra-scan mode reproducibility was 98-99%, corresponding to an LSC of 1.49-2.08%. The SDD was 0.018-0.023 g/cm(2) (lumbar spine) and 0.017-0.019 g/cm(2) (right femur). All comparisons among scan modes were statistically significant (p < 0.001) but lower than SDDs, i.e. not clinically relevant. Considering lumbar spine and the right femur, scan times were 50 and 38 s for fast array, 98 and 74 s for array, and 195 and 148 s for high definition, respectively; radiation doses were 6.7 and 4.7 μSv for fast array, and 13.3 and 9.3 μSv for both array and high definition, respectively., Conclusion: Since all BMD differences were lower than the SSDs, the three scan modes can be considered interchangeable. As a consequence, although the absolute reduction in time and radiation dose is relatively low, when BMD measurement is the aim of DXA, fast array can be generally preferred.

The aim of this study was to measure the effective dose on an anthropomorphic phantom undergoing lumbar and femoral dual energy X-ray absorption (DXA) examinations, using 3 different scan modalities (fast-array [FA], array [A], high-definition [HD]), and assess the differences in the lifetime attributable risk (LAR) of cancer due to radiation. An anthropomorphic phantom was used. Thermoluminescent dosimeters were placed over 12 anatomic phantom regions and outside the room (to measure background radiation). Fifty scans on the femur and spine were performed for each mode. The dose relative to a single DXA scan for each dosimeter was measured (mean over the 50 scans) and the background radiation was then subtracted. The equivalent dose per organ was obtained. The total body effective dose was calculated by adding the equivalent doses. We estimated the lifetime dose absorption and LAR for cancer for a male and a female patient undergoing 36 DXA studies (18 lumbar, 18 femoral) every 21 months for 32 years. The effective dose for lumbar scans was FA = 17.79 μSv, A = 32.88 μSv, HD = 31.08 μSv; for femoral scans, FA = 5.29 μSv, A = 9.55 μSv, HD = 7.54 μSv. LAR estimation showed a minimal increase in cancer risk (range 4.55 × 10⁻⁴% [FA, femoral, male] to 4.02 × 10⁻³% [A, lumbar, female]). The lifetime dose absorption and LAR for cancer for a male and a female patient undergoing 36 DXA studies (18 lumbar, 18 femoral) every 21 months for 32 years were 0.756 mSv, 3.82 × 10(-3)% and 0.756 mSv, 5.11 × 10⁻³%, respectively. DXA examinations cause radiation levels that are comparable to the background radiation. Regardless of the scan modality or the anatomic site, a patient undergoing DXA scans for a lifetime has a negligible increased risk of developing cancer., (Copyright © 2013 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

Background: Bone repair alteration is hypothesized for nonunion fracture pathogenesis. Since it is involved in osteoclast regulation, the RANK/RANKL/OPG system (receptor activator of nuclear factor kB/its ligand/osteoprotegerin) may play a role., Materials and Methods: Serum OPG, free RANKL, bone alkaline phosphatase (BAP), osteocalcin (OC), and urinary deoxypyridinoline (DPD) were determined in 16 male patients (20-39 years) with long bone atrophic nonunion fractures. Serum markers were also measured in 18 age-matched male controls who healed from the same type of fractures within six months, and in 14 age-matched male controls who were healing from the same fractures one month after injury. One-way ANOVA and Bonferroni's test were used for statistical analysis., Results: Only OPG was significantly higher (0.56 sd 0.11 ng/ml) in the patients compared to healed (0.26 sd 0.04 ng/ml; P < 0.001) and healing (0.29 sd 0.09 ng/ml; P < 0.001) controls. The patients' DPD levels were normal. No correlations were found between bone markers and the characteristics of the subjects in all groups., Conclusions: A normal steady state of bone metabolism seems to be present in patients with atrophic nonunion fractures, despite the high serum OPG. The reason for the inability of the patients' OPG to inhibit osteoclastic activity is unknown. Osteoblast activity also appears normal, so another cellular source of OPG can be hypothesized.