These results suggest that galectin-3 is involved in the pathogenesis of human IPF and CVD-IP by activating macrophages and fibroblasts.

The results suggest that UPD(20)mat underlies growth failure and feeding problems with additional features and could account for >5% of etiology-unknown SRS and small percentages of SGA-SS. Most important, this study provides an indication that UPD(20)mat can be associated with hypersensitivity of hormone receptors, which may gradually develop with age.

Background (Epi)genetic disorders associated with small-for-gestational-age with short stature (SGA-SS) include imprinting disorders (IDs). Silver-Russell syndrome (SRS) is a representative ID in SGA-SS and has heterogenous (epi)genetic causes. Subjects and Methods To clarify the contribution of IDs to SGA-SS and the molecular and phenotypic spectrum of SRS, we recruited 269 patients with SGA-SS consisting of 103 and 166 patients referred to us for genetic testing for SGA-SS and SRS, respectively. After excluding 20 patients with structural abnormalities detected by comparative genomic hybridization analysis using catalog array, 249 patients were classified into three subgroups based on the Netchine-Harbison clinical scoring system (NH-CSS), SRS diagnostic criteria. We screened various IDs by methylation analysis for differentially methylated regions (DMRs) related to known IDs. We also performed clinical analysis. Results These 249 patients with SGA-SS were classified into ‘SRS-compatible group’ (n=148), ‘non-SRS with normocephaly or relative macrocephaly at birth group’ (non-SRS group) (n=94), or ‘non-SRS with relative microcephaly at birth group’ (non-SRS with microcephaly group) (n=7). The 44.6% of patients in ‘SRS-compatible group’, 21.3% of patients in ‘non-SRS group’, and 14.3% in ‘non-SRS with microcephaly group’ had various IDs. Loss of methylation of the H19/IGF2:intergenic-DMR and uniparental disomy chromosome 7, being major genetic causes of SRS, were detected in 30.4% of patients in ‘SRS-compatible group’ and in 13.8% of patients in ‘non-SRS group’. Conclusion We clarified the contribution of IDs as (epi)genetic causes of SGA-SS and the molecular and phenotypic spectrum of SRS. Various IDs constitute underlying factors for SGA-SS, including SRS.

Loss of methylation (LOM) at GNAS-A/B:TSS-differentially methylated regions (DMRs) in the GNAS locus is observed in pseudohypoparathyroidism type 1B (PHP1B). Many PHP1B cases are sporadic, but autosomal dominant-PHP1B has a deletion involving NESP55 expressed from the maternal allele or STX16 located upstream of the GNAS locus on the maternal allele. We report the possible first familial PHP1B cases with retrotransposon insertion in the GNAS locus on the maternal allele. To our knowledge, they are the possible first cases with imprinting disorders caused by retrotransposon insertion. The two sibling cases experienced tetany and/or cramps from school age and had hypocalcemia and an increased serum intact parathyroid hormone (PTH) level together with overweight, round face, and normal intellectual levels. Methylation analysis for DMRs in the GNAS locus showed only LOM of the GNAS-A/B:TSS-DMR. Copy number abnormalities at STX16 and the GNAS locus were not detected by array comparative genomic hybridization. Whole-genome sequencing and Sanger sequencing revealed an approximately 1000-bp SVA retrotransposon insertion upstream of the first exon of A/B on the GNAS locus in these siblings. Whole-genome methylome analysis by Enzymatic Methyl-Seq in the siblings showed normal methylation status in the region surrounding the insertion site and mild LOM of the GNAS-A/B:TSS-DMR. We conducted transcriptome analysis using mRNA from skin fibroblasts and induced pluripotent stem cells (iPSCs) derived from the siblings and detected no aberrant NESP55 transcripts. Quantitative reverse-transcriptase PCR (qRT-PCR) analysis in skin fibroblasts showed increased A/B expression in the patients and no NESP55 expression, even in a control. qRT-PCR analysis in iPSCs showed decreased NESP55 expression with normal methylation status of the GNAS-NESP:TSS-DMR in the patients. The retrotransposon insertion in the siblings likely caused decreased NESP55 expression that could lead to increased A/B expression via LOM of the GNAS-A/B:TSS-DMR, subsequent reduced Gsα expression, and finally, PHP1B development.

We sequenced MKRN3, the major causative gene of central precocious puberty in Western countries, in 24 Japanese or Chinese patients and examined the DNA methylation and copy-number statuses of this gene in 19 patients. We identified no (epi)genetic defects except for one previously reported mutation. These results, together with reports from Korea, indicate that MKRN3 defects are rare in Asian populations. The ethnic differences likely reflect Western country-specific founder mutations and the rarity of de novo mutations.

Background For early‐stage non‐small cell lung cancer (NSCLC), surgical resection is considered the most effective treatment strategy and curative treatment. Unfortunately, even after complete resection, almost half of all patients with stage I–IIIA NSCLC relapse and die. Although the possibility of a cure for postoperative recurrence of NSCLC is significantly low, the course of subsequent treatment can possibly affect overall survival (OS). Here, we examined the association of relapse‐free survival (RFS) and post‐progression survival (PPS) with OS in patients with postoperative recurrence of NSCLC. Methods We evaluated 128 patients with NSCLC who underwent complete resection between January 2007 and December 2018. The association between RFS and PPS on OS was examined at the patient level. Results Spearman's rank correlation and linear regression analyses revealed that PPS was strongly correlated with OS (r = 0.83, p < 0.05, R2 = 0.72), whereas RFS was weakly associated with OS (r = 0.56, p < 0.05, R2 = 0.37). Additionally, the performance status at relapse and administration of tyrosine kinase inhibitors were significantly correlated with PPS. Conclusions PPS was significantly more strongly correlated with OS than was RFS in patients with postoperative recurrence of NSCLC. These results suggest that therapy following postoperative recurrence affects OS. Therefore, it is necessary to validate these promising results in a large prospective study.

We report a case of pulmonary adenocarcinoma metastasizing to the

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