:5; Personal non-commercial use only

ABSTRACT. Objective. We evaluated the whole-spine computed tomography (CT) findings in patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome to improve our understanding of this rare disease. Methods. Whole-spine CT images obtained in 69 patients with SAPHO were reviewed. For each individual, a total of 25 vertebrae were evaluated for the distribution of affected vertebrae, CT manifestations of vertebral lesions, symmetry and location of distribution of the lesions on vertebrae, involvement pattern, and narrowing of adjacent intervertebral disc space. Paravertebral ligamentous ossifications, apophyseal joint disorders, and costovertebral joint disorders were also evaluated. Results. All the 69 patients with SAPHO exhibited abnormalities on whole-spine CT. Sixty-four had vertebral lesions, 52 had paravertebral ossifications, and 47 had both. The vertebral lesions were observed in 441 vertebrae, with a predilection for thoracic spine. The lesions exhibited a mixture of cortical erosion, reactive osteosclerosis of surrounding cancellous bone, and syndesmophyte. They may be confined to the vertebral corner (65.1%) or be extensive, involving the endplate (34.9%). Corner lesions could start in any part of the epiphyseal ring. The lesions were asymmetrically distributed. The affected vertebrae were more consecutively involved in a "kissing" appearance (78.2%). Intervertebral disc spaces were usually normal or mildly narrowed. There were 320 foci of paravertebral ossifications observed, with a predilection for the supraspinous ligament. Paravertebral ossifications were delicate and segmental. Ossifications throughout annulus fibrosis and apophyseal joint were not observed. Conclusion. Our investigation of the distributional, morphological features and the involvement pattern of spinal lesions in patients with SAPHO demonstrated distinct CT characteristics

Personal non-commercial use only

ABSTRACT. Objective. We evaluated the whole-spine computed tomography (CT) findings in patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome to improve our understanding of this rare disease. Methods. Whole-spine CT images obtained in 69 patients with SAPHO were reviewed. For each individual, a total of 25 vertebrae were evaluated for the distribution of affected vertebrae, CT manifestations of vertebral lesions, symmetry and location of distribution of the lesions on vertebrae, involvement pattern, and narrowing of adjacent intervertebral disc space. Paravertebral ligamentous ossifications, apophyseal joint disorders, and costovertebral joint disorders were also evaluated. Results. All the 69 patients with SAPHO exhibited abnormalities on whole-spine CT. Sixty-four had vertebral lesions, 52 had paravertebral ossifications, and 47 had both. The vertebral lesions were observed in 441 vertebrae, with a predilection for thoracic spine. The lesions exhibited a mixture of cortical erosion, reactive osteosclerosis of surrounding cancellous bone, and syndesmophyte. They may be confined to the vertebral corner (65.1%) or be extensive, involving the endplate (34.9%). Corner lesions could start in any part of the epiphyseal ring. The lesions were asymmetrically distributed. The affected vertebrae were more consecutively involved in a "kissing" appearance (78.2%). Intervertebral disc spaces were usually normal or mildly narrowed. There were 320 foci of paravertebral ossifications observed, with a predilection for the supraspinous ligament. Paravertebral ossifications were delicate and segmental. Ossifications throughout annulus fibrosis and apophyseal joint were not observed. Conclusion. Our investigation of the distributional, morphological features and the involvement pattern of spinal lesions in patients with SAPHO demonstrated distinct CT characteristics

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Comprehensive prediction of immune microenvironment and hot and cold tumor differentiation in cutaneous melanoma based on necroptosis-related lncRNA

Abstract As per research, causing cancer cells to necroptosis might be used as a therapy to combat cancer drug susceptibility. Long non-coding RNA (lncRNA) modulates the necroptosis process in Skin Cutaneous Melanoma (SKCM), even though the precise mechanism by which it does so has yet been unknown. RNA sequencing and clinical evidence of SKCM patients were accessed from The Cancer Genome Atlas database, and normal skin tissue sequencing data was available from the Genotype-Tissue Expression database. Person correlation analysis, differential screening, and univariate Cox regression were successively utilized to identify necroptosis-related hub lncRNAs. Following this, we adopt the least absolute shrinkage and selection operator regression analysis to construct a risk model. The model was evaluated on various clinical characteristics using many integrated approaches to ensure it generated accurate predictions. Through risk score comparisons and consistent cluster analysis, SKCM patients were sorted either high-risk or low-risk subgroups as well as distinct clusters. Finally, the effect of immune microenvironment, m7G methylation, and viable anti-cancer drugs in risk groups and potential clusters was evaluated in further detail. Included USP30-AS1, LINC01711, LINC00520, NRIR, BASP1-AS1, and LINC02178, the 6 necroptosis-related hub lncRNAs were utilized to construct a novel prediction model with excellent accuracy and sensitivity, which was not influenced by confounding clinical factors. Immune-related, necroptosis, and apoptosis pathways were enhanced in the model structure, as shown by Gene Set Enrichment Analysis findings. TME score, immune factors, immune checkpoint-related genes, m7G methylation-related genes, and anti-cancer drug sensitivity differed significantly between the high-risk and low-risk groups. Cluster 2 was identified as a hot tumor with a better immune response and therapeutic effect. Our study may provide potential biomarkers for predicting prognosis in SKCM and provide personalized clinical therapy for patients based on hot and cold tumor classification

A novel signature for predicting prognosis and immune landscape in cutaneous melanoma based on anoikis-related long non-coding RNAs

Abstract Anoikis is a unique form of apoptosis associated with vascularization and distant metastasis in cancer. Eliminating anoikis resistance in tumor cells could be a promising target for improving the prognosis of terminal cancer patients. However, current studies have not elaborated on the prognosis effect of anoikis-related long non-coding RNAs (lncRNAs) in cutaneous melanoma. Pre-processed data, including RNA sequences and clinical information, were retrieved from TCGA and GTEx databases. After a series of statistical analyses, anoikis-related lncRNAs with prognostic significance were identified, and a unique risk signature was constructed. Risk scores were further analyzed in relation to the tumor microenvironment, tumor immune dysfunction and exclusion, immune checkpoint genes, and RNA methylation genes. The indicators were also used to predict the potentially sensitive anti-cancer drugs. An anoikis-related lncRNAs risk signature consisting of LINC01711, POLH-AS1, MIR205HG, and LINC02416 was successfully established in cutaneous melanoma. Overall survival and progression-free survival of patients were strongly linked with the risk score, independently of other clinical factors. The low-risk group exhibited a more beneficial immunological profile, was less affected by RNA methylation, and was more sensitive to the majority of anti-cancer drugs, all of which indicated a better prognostic outcome. The 4 hub lncRNAs may be fundamental to studying the mechanism of anoikis in cutaneous melanoma and provide personalized therapy for salvaging drug resistance

Microstructural Evolution of Wrought-Nickel-Based Superalloy GH4169

To investigate the microstructural evolution of wrought-nickel-based superalloy GH4169 from the original ingot to the finished product of manufacturing processes, different kinds of etchants and etching methods were used to show the fine precipitates and their morphologies. The obtained microstructures can vary in size, type, distribution, location, formation, and interactions of multiple phases, which were observed and analyzed by optical microscopy (OM), scanning electron microscopy (SEM), and an energy dispersive spectrometer (EDS). The dendrite segregation behavior of as-cast superalloy GH4169 was investigated. In addition, the microstructural evolution mechanism of second-phase particles during dynamic recrystallization was analyzed. This work sheds light on the evolution of the second-phase structure of nickel-based superalloys during the preparation process, providing guidance for process development and visual interpretation of the relationships between microstructure and properties

Expanding the mutation and phenotype spectrum of MYH3-associated skeletal disorders

Pathogenic variants in MYH3 cause distal arthrogryposis type 2A and type 2B3 as well as contractures, pterygia and spondylocarpotarsal fusion syndromes types 1A and 1B. These disorders are ultra-rare and their natural course and phenotypic variability are not well described. In this study, we summarize the clinical features and genetic findings of 17 patients from 10 unrelated families with vertebral malformations caused by dominant or recessive pathogenic variants in MYH3. Twelve novel pathogenic variants in MYH3 (NM_002470.4) were identified: three of them were de novo or inherited in autosomal dominant way and nine were inherited in autosomal recessive way. The patients had vertebral segmentation anomalies accompanied with variable joint contractures, short stature and dysmorphic facial features. There was a significant phenotypic overlap between dominant and recessive MYH3-associated conditions regarding the degree of short stature as well as the number of vertebral fusions. All monoallelic variants caused significantly decreased SMAD3 phosphorylation, which is consistent with the previously proposed pathogenic mechanism of impaired canonical TGF-beta signaling. Most of the biallelic variants were predicted to be protein-truncating, while one missense variant c.4244T&amp;gt;G,p.(Leu1415Arg), which was inherited in an autosomal recessive way, was found to alter the phosphorylation level of p38, suggesting an inhibition of the non-canonical pathway of TGF-beta signaling. In conclusion, the identification of 12 novel pathogenic variants and overlapping phenotypes in 17 affected individuals from 10 unrelated families expands the mutation and phenotype spectrum of MYH3-associated skeletal disorders. We show that disturbances of canonical or non-canonical TGF-beta signaling pathways are involved in pathogenesis of MYH3-associated skeletal fusion (MASF) syndrome.Funding Agencies|National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81930068, 81772299, 81822030, 82072391, 81972132, 81672123, 81972037, 81902178]; Beijing Natural Science FoundationBeijing Natural Science Foundation [JQ20032, 7191007]; CAMS Innovation Fund for Medical Sciences (CIFMS) [2021-I2M-1-051, 2021-I2M-1-052]; Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2019PT320025]; Tsinghua University-Peking Union Medical College Hospital Initiative Scientific Research Program; PUMC Youth Fund &amp; the Fundamental Research Funds for the Central Universities [3332019021]; Swedish Research CouncilSwedish Research CouncilEuropean Commission [K2015-54X-22 736-01-4, 2015-02227, 2018-03046]; Swedish Governmental Agency for Innovation Systems (Vinnova)Vinnova [2014-01438]; Marianne and Marcus Wallenberg Foundation; IngaBritt och Arne Lundbergs forskningsstiftelse; Byggmastare Olle Engkvist Stiftelse; Promobilia; Nyckelfonden; Stiftelsen Frimurare Barnhuset i Stockholm; Region Stockholm; Karolinska Institutet, Stockholm, Sweden; orebro University, orebro, Sweden; Sallskapet Barnavard; Karolinska InstitutetKarolinska Institutet; Stiftelsen Sallsyntafonden; Stiftelsen Samariten; Stiftelsen Promobilia; Region Stockholm [20180131, 20200500]; US National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke [NINDS R35 NS105078]; National Human Genome Research Institute/National Heart, Lung, and Blood Institute [NHGRI/NHLBI UM1 HG006542]; US NIH National Human Genome Research Institute [NHGRI K08 HG008986]</p

NTIRE 2019 Challenge on Real Image Denoising: Methods and Results

This paper reviews the NTIRE 2019 challenge on real image denoising with focus on the proposed methods and their results. The challenge has two tracks for quantitatively evaluating image denoising performance in (1) the Bayer- pattern raw-RGB and (2) the standard RGB (sRGB) color spaces. The tracks had 216 and 220 registered participants, respectively. A total of 15 teams, proposing 17 methods, competed in the final phase of the challenge. The proposed methods by the 15 teams represent the current state-of-the- art performance in image denoising targeting real noisy im- ages