Risk prediction model for long-term atelectasis in children with pneumonia.

BACKGROUND: This study aimed to develop a risk prediction model for long-term atelectasis in children with pneumonia. METHODS: A retrospective study of 532 children with atelectasis was performed at the Children's Hospital of Chongqing Medical University from February 2017 to March 2020. The predictive variables were screened by LASSO regression analysis and the nomogram was drawn by R software. The area under the Receiver Operating Characteristic (ROC) curve, calibration chart and decision curve were used to evaluate the predictive accuracy and clinical utility. 1000 Bootstrap resampling was used for internal verification. RESULTS: Multivariate logistic regression analysis showed that clinical course before bronchoscopy, length of stay, bronchial mucus plug formation, age were independent risk factors for long-term atelectasis in children. The area under the ROC curve of nomogram was 0.857(95% CI = 0.8136 ~ 0.9006) in training set and 0.849(95% CI = 0.7848-0.9132) in the testing set. The calibration curve demonstrated that the nomogram was well-fitted, and decision curve analysis (DCA) showed that the nomogram had good clinical utility. CONCLUSIONS: The model based on the risk factors of long-term atelectasis in children with pneumonia has good predictive accuracy and consistency, which can provide a certain reference value for clinical prevention and treatment of long-term atelectasis in children.

Four-Generation Pedigree of Monozygotic Female Twins Reveals Genetic Factors in Twinning Process by Whole-Genome Sequencing.

Familial monozygotic (MZ) twinning reports are rare around the world, and we report a four-generation pedigree with seven recorded pairs of female MZ twins. Whole-genome sequencing of seven family members was performed to explore the featured genetic factors in MZ twins. For variations specific to MZ twins, five novel variants were observed in the X chromosome. These candidates were used to explain the seemingly X-linked dominant inheritance pattern, and only one variant was exonic, located at the 5'UTR region of ZCCHC12 (chrX: 117958597, G > A). Besides, consistent mitochondrial DNA composition in the maternal linage precluded roles of mitochondria for this trait. In this pedigree, autosomes also contain diverse variations specific to MZ twins. Pathway analysis revealed a significant enrichment of genes carrying novel SNVs in the epithelial adherens junction-signaling pathway (p = .011), contributed by FGFR1, TUBB6, and MYH7B. Meanwhile, TBC1D22A, TRIOBP, and TUBB6, also carrying similar SNVs, were involved in the GTPase family-mediated signal pathway. Furthermore, gene-set enrichment analysis for 533 genes covered by copy number variations specific to MZ twins illustrated that the tight junction-signaling pathway was significantly enriched (p < .001). Therefore, the novel changes in the X chromosome and the provided candidate variants across autosomes may be responsible for MZ twinning, giving clues to increase our understanding about the underlying mechanism.

Common Postzygotic Mutational Signatures in Healthy Adult Tissues Related to Embryonic Hypoxia.

Postzygotic mutations are acquired in normal tissues throughout an individual's lifetime and hold clues for identifying mutagenic factors. Here, we investigated postzygotic mutation spectra of healthy individuals using optimized ultra-deep exome sequencing of the time-series samples from the same volunteer as well as the samples from different individuals. In blood, sperm, and muscle cells, we resolved three common types of mutational signatures. Signatures A and B represent clock-like mutational processes, and the polymorphisms of epigenetic regulation genes influence the proportion of signature B in mutation profiles. Notably, signature C, characterized by C>T transitions at GpCpN sites, tends to be a feature of diverse normal tissues. Mutations of this type are likely to occur early during embryonic development, supported by their relatively high allelic frequencies, presence in multiple tissues, and decrease in occurrence with age. Almost none of the public datasets for tumors feature this signature, except for 19.6% of samples of clear cell renal cell carcinoma with increased activation of the hypoxia-inducible factor 1 (HIF-1) signaling pathway. Moreover, the accumulation of signature C in the mutation profile was accelerated in a human embryonic stem cell line with drug-induced activation of HIF-1α. Thus, embryonic hypoxia may explain this novel signature across multiple normal tissues. Our study suggests that hypoxic condition in an early stage of embryonic development is a crucial factor inducing C>T transitions at GpCpN sites; and individuals' genetic background may also influence their postzygotic mutation profiles.

Rapid automated materials synthesis instrument: exploring the composition and heat-treatment of nanoprecursors toward low temperature red phosphors.

We report on the commissioning experimental run of the rapid automated materials synthesis instrument (RAMSI), a combinatorial robot designed to manufacture, clean, and print libraries of nanocrystal precursor solid compositions. The first stage of RAMSI, parallel synthesis, uses a fully automated high throughput continuous hydrothermal (HiTCH) flow reactor for automatic metal salt precursor mixing, hydrothermal flow reaction, and sample slurry collection. The second stage of RAMSI provides integrated automated cleanup, and the third section is a ceramic printing function. Nanocrystal precursor solid ceramics were synthesized from precursor solutions and collected into 50 mL centrifuge tubes where they were cleaned by multiple centrifugation and redispersion cycles (monitored by intelligent scanning turbidimetry) and printed with an automated pipette. Eight unique compositions of a model phosphor library comprising pure nano-Y(OH)(3) and Eu(3+) doped-yttrium hydroxide, Y(OH)(3):Eu(3+) nanocrystal precursor solid were synthesized (with 2 centrifuge tubes' worth collected per composition), processed, and printed in duplicate as 75, 100, and 125 microL dots in a 21.6 ks (6 h) experiment (note: the actual time for synthesis of each sample tube was only 12 min so up to 60 compositions could easily be synthesized in 12 h if one centrifuge tube per composition was collected instead). The Y(OH)(3):Eu(3+) samples were manually placed in a furnace and heat-treated in air for 14.4 ks (4 h) in the temperature range 200-1200 at 100 degrees C intervals (giving a total of 84 samples plus one as-prepared pure Y(OH)(3) sample). The as-prepared and heat-treated ceramic samples were affixed to 4 mm wide hemispherical wells in a custom-made aluminum well-plate and analyzed using a fluorescence spectrometer. When the library was illuminated with a 254 nm light source (and digitally imaged and analyzed), the 3 mol % Eu(3+) sample heat-treated at 1200 degrees C gave the most intense fluorescence (major red peak at 612 nm); however, an identical nanocrystal precursor heat-treated at only 500 degrees C (identified as Y(2)O(3):Eu(3+) after heat treatment) was the brightest phosphor under illumination of the samples heat-treated at or below 1000 degrees C.

Characterization and drug release investigation of amorphous drug-hydroxypropyl methylcellulose composites made via supercritical carbon dioxide assisted impregnation.

Hydroxypropylmethyl cellulose (HPMC)-indomethacin (4:1, w/w) drug composites (DCs) were prepared via supercritical carbon dioxide (sc-CO(2)) assisted impregnation. The effect of processing temperature (at fixed pressures) on the physical and other properties of the resulting HPMC-indomethacin DCs was investigated using a range of analytical techniques, including differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, Raman spectroscopy, and powder X-ray diffraction (XRD) methods. The data suggest that for a 4:1 (w/w) HPMC-indomethacin ratio prepared at 130 degrees C (17.2 MPa), the indomethacin exists entirely in an amorphous dispersion within the polymer matrix. The primary interaction between HPMC and indomethacin appears to be hydrogen bonding between the carboxylic acid carbonyl group of indomethacin and hydroxyl group of HPMC. The initial (first 15 min) and overall drug release behavior within a 5h timeframe for the HPMC-indomethacin DCs, was analyzed. For the HPMC-indomethacin drug composite processed at 130 degrees C/17.2 MPa, drug release behavior obeyed a n-power law (n=0.54).

Screening analysis of candidate gene mutations in a kindred with polycystic liver disease.

AIM: To find potential mutable sites by detecting mutations of the candidate gene in a kindred with polycystic liver disease (PCLD). METHODS: First, we chose a kindred with PCLD and obtained five venous blood samples of this kindred after the family members signed the informed consent form. In the kindred two cases were diagnosed with PCLD, and the left three cases were normal individuals. All the blood samples were preserved at -85 °C. Second, we extracted the genomic DNA from the venous blood samples of the kindred using a QIAamp DNA Mini Kit and then performed long-range polymerase chain reaction (PCR) with different primers. The exons of PKD1 were all sequenced with the forward and reverse primers to ensure the accuracy of the results. Next, we purified the PCR products and directly sequenced them using Big Dye Terminator Chemistry version 3.1. The sequencing reaction was conducted with BiomekFX (Beckman). Finally, we analyzed the results. RESULTS: A total of 42 normal exons were identified in detecting mutations of the PKD1 gene. A synonymous mutation occurred in exon 5. The mutation was a homozygous T in the proband and was C in the reference sequence. This mutation was located in the third codon and did not change the amino acid encoded by the codon. Missense mutations occurred in exons 11 and 35. These mutations were located in the second codon; they changed the amino acid sequence and existed in the dbSNP library. A nonsense mutation occurred in exon 15. The mutation was a heterozygous CT in the proband and was C in the reference sequence. This mutation was located in the first codon and resulted in a termination codon. This mutation had an obvious influence on the encoded protein and changed the length of the protein from 4303 to 2246 amino acids. This was a new mutation that was not present in the dbSNP library. CONCLUSION: The nonsense mutation of exon 15 existed in the proband and in the third individual. Additionally, the proband was heterozygous for this mutation, so the mutable site was a pathogenic mutation.

An Old Story Retold: Loss of G1 Control Defines A Distinct Genomic Subtype of Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) has a high mortality rate. To determine the molecular basis of ESCC development, this study sought to identify characteristic genome-wide alterations in ESCC, including exonic mutations and structural alterations. The clinical implications of these genetic alterations were also analyzed. Exome sequencing and verification were performed for nine pairs of ESCC and the matched blood samples, followed by validation with additional samples using Sanger sequencing. Whole-genome SNP arrays were employed to detect copy number alteration (CNA) and loss of heterozygosity (LOH) in 55 cases, including the nine ESCC samples subjected to exome sequencing. A total of 108 non-synonymous somatic mutations (NSSMs) in 102 genes were verified in nine patients. The chromatin modification process was found to be enriched in our gene ontology (GO) analysis. Tumor genomes with TP53 mutations were significantly more unstable than those without TP53 mutations. In terms of the landscape of genomic alterations, deletion of 9p21.3 covering CDKN2A/2B (30.9%), amplification of 11q13.3 covering CCND1 (30.9%), and TP53 point mutation (50.9%) occurred in two-thirds of the cases. These results suggest that the deregulation of the G1 phase during the cell cycle is a key event in ESCC. Furthermore, six minimal common regions were found to be significantly altered in ESCC samples and three of them, 9p21.3, 7p11.2, and 3p12.1, were associated with lymph node metastasis. With the high correlation of TP53 mutation and genomic instability in ESCC, the amplification of CCND1, the deletion of CDKN2A/2B, and the somatic mutation of TP53 appear to play pivotal roles via G1 deregulation and therefore helps to classify this cancer into different genomic subtypes. These findings provide clinical significance that could be useful in future molecular diagnoses and therapeutic targeting.

Birt-Hogg-Dubé syndrome with clear cell renal cell carcinoma in a Chinese family.

Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal dominant genodermatosis that presents as a clinical triad including follicular hamartomas, renal neoplasms and lung cysts associated with an increased risk of pneumothorax. FLCN gene defects have been identified as being responsible for BHDS. We herein report the case of a 67-year-old woman with the full-blown BHDS phenotype, characterized by skin lesions, multiple lung bullae and renal neoplasms. In her family history, one of the patient's sons exhibited a similar phenotype, without renal neoplasms. Due to the relatively late age of onset of renal neoplasms among variable BHDS phenotypes, follow-up imaging is recommended for the son who has not yet developed renal neoplasms.

Phase stability and rapid consolidation of hydroxyapatite-zirconia nano-coprecipitates made using continuous hydrothermal flow synthesis.

A rapid and continuous hydrothermal route for the synthesis of nano-sized hydroxyapatite rods co-precipitated with calcium-doped zirconia nanoparticles using a superheated water flow at 450°C and 24.1 MPa as a crystallizing medium is described. Hydroxyapatite and calcium-doped zirconia phases in the powder mixtures could be clearly identified based on particle size and morphology under transmission electron microscopy. Retention of a nanostructure after sintering is crucial to load-bearing applications of hydroxyapatite-based ceramics. Therefore, rapid consolidation of the co-precipitates was investigated using a spark plasma sintering furnace under a range of processing conditions. Samples nominally containing 5 and 10 wt% calcium-doped zirconia and hydroxyapatite made with Ca:P solution molar ratio 2.5 showed excellent thermal stability (investigated using in situ variable temperature X-ray diffraction) and were sintered via spark plasma sintering to >96% sintered densities at 1000°C resulting in hydroxyapatite and calcium-doped zirconia as the only two phases. Mechanical tests of spark plasma sintering sintered samples (containing 10 wt% calcium-doped zirconia) revealed a three-pt flexural strength of 107.7 MPa and Weibull modulus of 9.9. The complementary nature of the spark plasma sintering technique and continuous hydrothermal flow synthesis (which results in retention of a nanostructure even after sintering at elevated temperatures) was hence showcased.

High-strength nanograined and translucent hydroxyapatite monoliths via continuous hydrothermal synthesis and optimized spark plasma sintering.

The synthesis of high-strength, completely dense nanograined hydroxyapatite (bioceramic) monoliths is a challenge as high temperatures or long sintering times are often required. In this study, nanorods of hydroxyapatite (HA) and calcium-deficient HA (made using a novel continuous hydrothermal flow synthesis method) were consolidated using spark plasma sintering (SPS) up to full theoretical density in ∼5 min at temperatures up to 1000°C. After significant optimization of the SPS heating and loading cycles, fully dense HA discs were obtained which were translucent, suggesting very high densities. Significantly high three-point flexural strength values for such materials (up to 158 MPa) were measured. Freeze-fracturing of disks followed by scanning electron microscopy investigation revealed selected samples possessed sub-200 nm sized grains and no visible pores, suggesting they were fully dense.

High-throughput continuous hydrothermal flow synthesis of Zn-Ce oxides: unprecedented solubility of Zn in the nanoparticle fluorite lattice.

High-throughput continuous hydrothermal flow synthesis has been used as a rapid and efficient synthetic route to produce a range of crystalline nanopowders in the Ce-Zn oxide binary system. High-resolution powder X-ray diffraction data were obtained for both as-prepared and heat-treated (850 degrees C for 10 h in air) samples using the new robotic beamline I11, located at Diamond Light Source. The influence of the sample composition on the crystal structure and on the optical and physical properties was studied. All the nanomaterials were characterized using Raman spectroscopy, UV-visible spectrophotometry, Brunauer-Emmett-Teller surface area and elemental analysis (via energy-dispersive X-ray spectroscopy). Initially, for 'as-prepared' Ce(1-x)Zn(x)O(y), a phase-pure cerium oxide (fluorite) structure was obtained for nominal values of x=0.1 and 0.2. Biphasic mixtures were obtained for nominal values of x in the range of 0.3-0.9 (inclusive). High-resolution transmission electron microscopy images revealed that the phase-pure nano-CeO(2) (x=0) consisted of ca 3.7 nm well-defined nanoparticles. The nanomaterials produced herein generally had high surface areas (greater than 150 m(2) g(-1)) and possessed combinations of particle properties (e.g. bandgap, crystallinity, size, etc.) that were unobtainable or difficult to achieve by other more conventional synthetic methods.