Peripheral pulmonary arterial stenosis (PPAS) is commonly observed in paediatric patients with associated congenital heart disease or systemic congenital syndromes, such as tetralogy of Fallot and Williams syndrome [1]. Meanwhile, isolated PPAS without other structural heart disease or systemic congenital syndromes is primarily reported in adulthood [2]. Recent genetic analyses have revealed that four cases of isolated PPAS in adulthood were homozygous for the ring finger protein 213 (RNF213) p.Arg4810Lys variant (also referred to as G to A alteration of rs112735431 and NM_001256071.3:c.14429G>A) [3]. RNF213 p.Arg4810Lys is a genetic determinant in moyamoya disease (MMD) in East Asians [4]. This genetic variant is unique to East Asians and is reported to have a frequency of approximately 0.8% in the general Japanese population [5, 6]. However, its prevalence in adult patients with isolated PPAS remains unknown.

Background: The influenza vaccine administrated every year is a recommended infection control procedure for individuals above the age of six months. However, the effectiveness of repeated annual vaccination is still an active research topic. Therefore, we investigated the vaccine immunogenicity in two independent groups: previously vaccinated versus non-vaccinated individuals at three time points; prior vaccination, one week and three months post vaccination. The assessment enabled us to evaluate the elicited immune responses and the durability of the induced protection in both groups.Research Design and Methods: A research study was conducted to assess the immunogenicity of a single dose of Trivalent Inactivated Influenza Vaccine (A/H1N1, A/H3N2, and B) in 278 healthy adults aged between 32 and 66 years. Almost half of the participants, 140 (50 center dot 36%), received influenza vaccination at least once precursor to past influenza seasons. One blood sample was taken prior to vaccination for complete blood analysis and baseline immunogenicity assessment. The selected study participants received a single vaccine dose on the first day, and then followed up for three months. Two blood samples were taken after one week and three months post vaccination, respectively, for vaccine immunogenicity assessment.Results: Before vaccination, the seroprotection, defined as a hemagglutination-inhibiting titer of =>1:40, was detected for the three vaccine virus strains in 20 previously vaccinated participants (1429%) [895%, 212%]. We compared the overall vaccine response for the three virus strains using a normalized response score calculated from linearly transformed titer measurements; the score before vaccination was 84% higher in the previously vaccinated group and the mean difference between the two groups was statistically significant. Three months post-vaccination, we didn't find a significant difference in vaccine responses; the number of fully seroprotected individuals became 48 (3429%) [2648%, 4277%] in the previously vaccinated group and 59 (4275%) [3437%, 5145%] in the non-vaccinated group. The calculated response score was almost equal in both groups and the mean difference was no longer statistically significant.Conclusion: Our findings suggest that a single dose of influenza vaccine is equally protective after three months for annually vaccinated adults and first-time vaccine receivers.

Context: Monogenic diabetes is often underdiagnosed because of limited genetic testing opportunities and varying screening criteria. Objective: To investigate the genetic and clinical characteristics of monogenic diabetes in Japan and assess the utility of classical screening criteria and the maturity-onset diabetes of the young (MODY) probability calculator. Design and Setting: This study included a total of 232 probands with diabetes onset before age 35, BMI <30 kg/m², and negative islet autoantibodies, recruited from 2019 to 2024. Targeted sequencing of 11 causal genes was performed, followed by multiplex ligation-dependent probe amplification when indicated. Results: Pathogenic or likely pathogenic (P/LP) variants were identified in 67 (28.9%) probands: 25 in GCK, 22 in HNF1A, 7 in HNF1B, 6 in HNF4A, 4 in ABCC8, and 1 each in NEUROD1, PDX1, and INSR. Of these, 64 (95.5%) carried variants in actionable genes potentially affecting treatment strategies (GCK, HNF1A, HNF1B, HNF4A, ABCC8). P/LP carriers were younger at diagnosis, had lower BMI, and better metabolic control than noncarriers. However, clinical heterogeneity was substantial. Notably, 35 cases (52.2%) did not meet classical screening criteria of young-onset (≤25 years) and a three-generation family history. Although MODY probability scores were higher in probands with P/LP carriers (median: 75.5% vs. 58.0%; P <0.001), early insulin initiation substantially lowered the probability scores, warranting caution. Conclusion: We established a nationwide genetic testing platform and identified carriers of actionable variants, offering possibilities for precision medicine. Neither classical criteria nor the MODY calculator identified all monogenic cases, highlighting the need for broader genetic testing.

The seasonal influenza vaccine remains one of the vital recommended infection control measures for the elderly with chronic illnesses. We investigated the immunogenicity of a single dose of influenza vaccine in 123 seronegative participants and classified them into four distinct groups, determined by the promptness of vaccine response, the longevity of humoral immunity, and the likelihood of exhibiting cross-reactivity. Subsequently, we used transcriptional profiling and differential gene expression analysis to identify potential genes directly associated with the robust response to the vaccine. The group of exemplary vaccine responders differentially expressed 16 genes, namely: MZB1, MYDGF, TXNDC5, TXNDC11, HSP90B1, FKBP11, PDIA5, PRDX4, CD38, SDC1, TNFRSF17, TNFRSF13B, PAX5, POU2AF1, IRF4, and XBP1. Our findings point out a list of expressed proteins that are related to B cell proliferation, unfolded protein response, and cellular haemostasis, as well as a linkage of these expressions to the survival of long-lived plasma cells.

Esotropia and exotropia in the entity of comitant strabismus are multifactorial diseases with both genetic and environmental backgrounds. Idiopathic superior oblique muscle palsy, as the predominant entity of non-comitant (paralytic) strabismus, also has a genetic background, as evidenced by varying degrees of muscle hypoplasia. A genome-wide association study (GWAS) was conducted of 711 Japanese patients with esotropia (n= 253), exotropia (n = 356), and idiopathic superior oblique muscle palsy (n = 102). The genotypes of single nucleotide polymorphisms (SNPs) were determined by Infinium Asian Screening Array. Three control cohorts from the Japanese population were used: two cohorts from BioBank Japan (BBJ) and the Nagahama Cohort. BBJ (180K) was genotyped by a different array, Illumina Infinium OmniExpressExome or HumanOmniExpress, while BBJ (ASA) and the Nagahama Cohort were genotyped by the same Asian array. After quality control of SNPs and individuals, common SNPs between the case cohort and the control cohort were chosen in the condition of genotyping by different arrays, while all SNPs genotyped by the same array were used for SNP imputation. The SNPs imputed with R-square values ≥ 0.3 were used to compare the case cohort of each entity or the combined entity with the control cohort. In comparison with BBJ (180K), the esotropia group and the exotropia group showed CDCA7 and HLA-F, respectively, as candidate genes at a significant level of p < 5 × 10⁻⁸, while the idiopathic superior oblique muscle palsy group showed DAB1 as a candidate gene which is involved in neuronal migration. DAB1 was also detected as a candidate in comparison with BBJ (ASA) and the Nagahama Cohort at a weak level of significance of p < 1 × 10⁻⁶. In comparison with BBJ (180K), RARB (retinoic acid receptor-β) was detected as a candidate at a significant level of p < 5 × 10⁻⁸ in the combined group of esotropia, exotropia, and idiopathic superior oblique muscle palsy. In conclusion, a series of GWASs with three different control cohorts would be an effective method with which to search for candidate genes for multifactorial diseases such as strabismus.

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