Keep You Safe

Yui, a bright-eyed Japanese woman, moves to America and thinks she finds her Prince Charming in a small Iowa town. She falls in love and into a trap, staged by his white nationalist family who use her as a pawn in their terrorist plan

Novel PTCH1 mutation in Gorlin syndrome

Gorlin syndrome is an autosomal dominant disorder characterized by a wide range of developmental abnormalities and a predisposition to various tumors, and it is linked to the alteration of several causative genes, including PTCH1. We performed targeted resequencing using a next-generation sequencer to analyze genes associated with known clinical phenotypes in an 11-year-old male with sporadic jaw keratocysts. A novel duplication mutation (c.426dup) in PTCH1, resulting in a truncated protein, was identified

Novel CLCN7 mutations in IARO

Osteopetrosis is a heritable disorder of the skeleton that is characterized by increased bone density on radiographs caused by defects in osteoclast formation and function. Mutations in >10 genes are identified as causative for this clinically and genetically heterogeneous disease in humans. We report two novel missense variations in a compound heterozygous state in the CLCN7 gene, detected through targeted exome sequencing, in a 15-year-old Japanese female with intermediate autosomal recessive osteopetrosis

A case with concurrent duplication, triplication, and uniparental isodisomy at 1q42.12-qter supporting microhomology-mediated break-induced replication model for replicative rearrangements

Background: Complex genomic rearrangements (CGRs) consisting of interstitial triplications in conjunction with uniparental isodisomy (isoUPD) have rarely been reported in patients with multiple congenital anomalies (MCA)/intellectual disability (ID). One-ended DNA break repair coupled with microhomology-mediated break-induced replication (MMBIR) has been recently proposed as a possible mechanism giving rise to interstitial copy number gains and distal isoUPD, although only a few cases providing supportive evidence in human congenital diseases with MCA have been documented. Case presentation: Here, we report on the chromosomal microarray (CMA)-based identification of the first known case with concurrent interstitial duplication at 1q42.12-q42.2 and triplication at 1q42.2-q43 followed by isoUPD for the remainder of chromosome 1q (at 1q43-qter). In distal 1q duplication/triplication overlapping with 1q42.12-q43, variable clinical features have been reported, and our 25-year-old patient with MCA/ID presented with some of these frequently described features. Further analyses including the precise mapping of breakpoint junctions within the CGR in a sequence level suggested that the CGR found in association with isoUPD in our case is a triplication with flanking duplications, characterized as a triplication with a particularly long duplication-inverted triplication-duplication (DUP-TRP/INV-DUP) structure. Because microhomology was observed in both junctions between the triplicated region and the flanking duplicated regions, our case provides supportive evidence for recently proposed replication-based mechanisms, such as MMBIR, underlying the formation of CGRs + isoUPD implicated in chromosomal disorders. Conclusions: To the best of our knowledge, this is the first case of CGRs + isoUPD observed in 1q and having DUP-TRP/INV-DUP structure with a long proximal duplication, which supports MMBIR-based model for genomic rearrangements. Molecular cytogenetic analyses using CMA containing single-nucleotide polymorphism probes with further analyses of the breakpoint junctions are recommended in cases suspected of having complex chromosomal abnormalities based on discrepancies between clinical and conventional cytogenetic findings

Study on joint characteristics in laser butt welding of AMed and wrought Ti6Al4V plates

Titanium alloy Ti6Al4V has been widely applied to medical, automotive, and aerospace industries due to its excellent properties such as high strength and excellent corrosion resistance. On the other hand, additive manufacturing (AM) technology can give the freedom of design of the products. In order to spread the AMed products, the joining of AMed and wrought products are required, and it is important to understand the joint characteristics. In this study, butt welding of Ti6Al4V plate was conducted by fiber laser in argon shielding, and the joint characteristics of laser weld wrought/wrought, AMed/AMed, and AMed/wrought Ti6Al4V plates were experimentally investigated. The AMed plate has higher tensile strength than wrought plate but the elongation of AMed plate is smaller, since AMed plate has α’ martensite due to rapid cooling during laser irradiation in AM process. Then, the laser weld joint of AMed/AMed plates has higher tensile strength, but smaller elongation than that of wrought/wrought plates. The weld joint of AMed/wrought plates shows good welding state, since small heat input leads to formation of small weld bead with higher hardness between wrought and AMed plates

Analysis of Purine Metabolism to Elucidate the Pathogenesis of Acute Kidney Injury in Renal Hypouricemia

博士（医学）甲日本医科大学202

Skin microbiome profile in people living with HIV/AIDS in Cameroon

The presence of pathogens and the state of diseases, particularly skin diseases, may alter the composition of human skin microbiome. HIV infection has been reported to impair gut microbiome that leads to severe consequences. However, with cutaneous manifestations, that can be life-threatening, due to the opportunistic pathogens, little is known whether HIV infection might influence the skin microbiome and affect the skin homeostasis. This study catalogued the profile of skin microbiome of healthy Cameroonians, at three different skin sites, and compared them to the HIV-infected individuals. Taking advantage on the use of molecular assay coupled with next-generation sequencing, this study revealed that alpha-diversity of the skin microbiome was higher and beta-diversity was altered significantly in the HIV-infected Cameroonians than in the healthy ones. The relative abundance of skin microbes such as Micrococcus and Kocuria species was higher and Cutibacterium species was significantly lower in HIV-infected people, indicating an early change in the human skin microbiome in response to the HIV infection. This phenotypical shift was not related to the number of CD4 T cell count thus the cause remains to be identified. Overall, these data may offer an important lead on the role of skin microbiome in the determination of cutaneous disease state and the discovery of safe pharmacological preparations to treat microbial-related skin disorders

Safety and Efficacy of FIT039 for Verruca Vulgaris: A Placebo-Controlled, Phase I/II Randomized Controlled Trial

TRIAL DESIGN: Human papillomavirus infection causes verruca vulgaris. CDK9 inhibitor FIT039 inhibits DNA virus proliferation in animal models. We conducted a multicenter, single-blind, placebo-controlled, randomized phase I/II clinical trial evaluating the safety and efficacy of FIT039 against verruca vulgaris. METHODS: Target lesions were treated with liquid nitrogen once, and a FIT039 patch or placebo patch was applied for 14 days. The primary endpoint was lesion disappearance. The secondary endpoints were safety and changes in dimension, cross-sectional area, and the number of petechial lesions. RESULTS: A total of 24 participants were randomly allocated to the FIT039 (n = 13, median age, 54 years) and placebo (n = 11, median age, 62 years) groups. Verruca vulgaris did not disappear. FIT039 decreased the dimension to 76% of the initial value on day 29, followed by an increase to 98% on day 57. Placebo showed a monotonic increase to 107% on day 57. Changes in the cross-sectional area and petechiae number were comparable between the groups. CONCLUSIONS: No drug-related adverse reactions occurred. FIT039 efficacy was not determined in this study

Onset mechanism of a female patient with Dent disease 2

Background Approximately 15% of patients with Dent disease have pathogenic variants in theOCRLgene on Xq25-26, a condition that is referred to as Dent disease 2 (Dent-2). Dent-2 patients sometimes show mild extrarenal features of Lowe syndrome, such as mild mental retardation, suggesting that Dent-2 represents a mild form of Lowe syndrome. To date, eight female patients with Lowe syndrome have been reported, but no female Dent-2 patients have been reported. Methods In this study, we performed genetic testing of the first female Dent-2 patient to detect the presence of anOCRLvariant. Aberrant splicing was demonstrated by in vivo, in vitro, and in silico assays, and skewed X-chromosome inactivation (XCI) in our patient and asymptomatic mothers of three Lowe patients with the heterozygousOCRLvariant was evaluated by HUMARA assays using genomic DNA and RNA expression analysis. Results Our patient had anOCRLheterozygous intronic variant of c.1603-3G > C in intron 15 that led to a 169-bp insertion in exon 16, yielding the truncating mutation r.1602_1603ins (169) (p.Val535Glyfs*6) in exon 16. HUMARA assays of leukocytes obtained from this patient demonstrated incompletely skewed XCI (not extremely skewed). On the other hand, the asymptomatic mothers of 3 Lowe patients demonstrated random XCI. These results may lead to our patient's Dent-2 phenotype. Conclusions This is the first report of a female patient clinically and genetically diagnosed with Dent-2 caused by anOCRLheterozygous splicing site variant and skewed XCI. Skewed XCI may be one of the factors associated with phenotypic diversity in female patients with Lowe syndrome and Dent-2

Laser butt welding of thin Ti6Al4V sheets: Effects of welding parameters

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