Genetic etiology of truncus arteriosus excluding 22q11.2 deletion syndrome and identification of c.1617del, a prevalent variant in TMEM260, in the Japanese population.

Truncus Arteriosus (TA) is a congenital heart disease characterized by a single common blood vessel emerging from the right and left ventricles instead of the main pulmonary artery and aorta. TA accounts for 4% of all critical congenital heart diseases. The most common cause of TA is 22q11.2 deletion syndrome, accounting for 12-35% of all TA cases. However, no major causes of TA other than 22q11.2 deletion have been reported. We performed whole-genome sequencing of 11 Japanese patients having TA without 22q11.2 deletion. Among five patients, we identified pathogenic variants in TMEM260; the biallelic loss-of-function variants of which have recently been associated with structural heart defects and renal anomalies syndrome (SHDRA). In one patient, we identified a de novo pathogenic variant in GATA6, and in another patient, we identified a de novo probably pathogenic variant in NOTCH1. Notably, we identified a prevalent variant in TMEM260 (ENST00000261556.6), c.1617del (p.Trp539Cysfs*9), in 8/22 alleles among the 11 patients. The c.1617del variant was estimated to occur approximately 23 kiloyears ago. Based on the allele frequency of the c.1617del variant in the Japanese population (0.36%), approximately 26% of Japanese patients afflicted with TA could harbor homozygous c.1617del variants. This study highlights TMEM260, especially c.1617del, as a major genetic cause of TA in the Japanese population.

Clinical Prognosis of Vocal Cord Paralysis After Cardiothoracic Surgery in Infants.

We aimed to clarify the long-term outcomes and prognosis of vocal cord paralysis (VCP) after cardiothoracic surgery in infants as well as the usefulness of laryngeal ultrasound (LUS) as screening for VCP. Overall, 967 infants aged 1-year-old or younger who underwent cardiothoracic surgery between 2008 and 2022 were included in this study. We divided the patients into two groups based on the period on whether they underwent screening without or with LUS and compared the incidence of VCP between the groups. There were no differences in the patients' preoperative characteristics between the two periods, whereas the incidence of VCP was significantly higher in period 2 than in period 1 (11.0% vs. 3.2%, p < 0.0001). The incidence of VCP among the procedures, including aortic arch repair, was > 50% and significantly increased from period 1 to period 2. The sensitivity and specificity of LUS was 87% and 90%, respectively. Symptoms of VCP improved in 92% of patients. Repeated flexible laryngoscopy revealed that the residual rate of VCP was 68%, 52%, and 48% at 6, 12, and 24 months, respectively. In conclusion, symptoms of postoperative VCP improved in most cases; however, paralysis persisted in half of the patients. As a screening method, LUS is useful for evaluating postoperative VCP. A more accurate understanding of VCP is needed to improve postoperative outcomes.

Multi-pass-cell-based nonlinear pulse compression to 115 fs at 7.5 µJ pulse energy and 300 W average power.

We demonstrate nonlinear pulse compression by multi-pass cell spectral broadening (MPCSB) from 860 fs to 115 fs with compressed pulse energy of 7.5 µJ, average power of 300 W and close to diffraction-limited beam quality. The transmission of the compression unit is >90%. The results show that this recently introduced compression scheme for peak powers above the threshold for catastrophic self-focusing can be scaled to smaller pulse energies and can achieve a larger compression factor than previously reported. Good homogeneity of the spectral broadening across the beam profile is verified, which distinguishes MPCSB among other bulk compression schemes.

A case of retroperitoneal fibrosis responding to steroid therapy.

A 69-year-old man presented at the hospital with complaints of prolonged stomach pain extending from the week prior. Enhanced computed tomography (CT) revealed a low density area in the retroperitoneal space. A radiologist diagnosed the patient with retroperitoneal fibrosis. One week later, an enhanced CT revealed an exponential increase of the low density area and slight right hydronephrosis. Upon admission, prednisolone administration was initiated at a dose of 40mg/day. The size of the retroperitoneal soft tissue mass decreased gradually. Although the dose of prednisolone was tapered to 5mg, the patient is doing well without any sign of recurrence.

Doppler Cooling Trapped Ions with a UV Frequency Comb.

We demonstrate Doppler cooling of trapped magnesium ions using a frequency comb at 280 nm obtained from a frequency tripled Ti:sapphire laser. A comb line cools on the 3s_{1/2}-3p_{3/2} transition, while the nearest blue-detuned comb line contributes negligible heating. We observe the cooling-heating transition and long-term cooling of ion chains with several sympathetically cooled ions. Spatial thermometry shows that the ion is cooled to near the Doppler limit. Doppler cooling with frequency combs has the potential to open many additional atomic species to laser cooling by reaching further into the vacuum and extreme ultraviolet via high-harmonic generation and by providing a broad bandwidth from which multiple excitation sidebands can be obtained.

High average power coherent vuv generation at 10 MHz repetition frequency by intracavity high harmonic generation.

Intracavity high harmonic generation was utilized to generate high average-power coherent radiation at vacuum ultraviolet (vuv) wavelengths. A ytterbium-doped fiber-laser based master-oscillator power-amplifier (MOPA) system with a 10 MHz repetition frequency was developed and used as a driving laser for an external cavity. A series of odd-order harmonic radiations was generated extending down to ∼ 30 nm (41 eV in photon energy). The 7th harmonic radiation generated was centered at 149 nm and had an average output power of up to 0.5 mW. In this way, we developed a sub-mW coherent vuv-laser with a 10 MHz repetition frequency, which, if used as an excitation laser source for photo-electron spectroscopy, could improve the signal count-rate without deterioration of the spectral-resolution caused by space-charge effects.

A case of dedifferentiated liposarcoma discovered due to an intrascrotal calcified ossification.

Dedifferentiated liposarcoma is a rare cancer with a poor prognosis. A 52-year-old man presented with a chief complaint of a mass in his left scrotum. He came with suspected testicular tumor, but all the measured tumor markers were negative. Imaging test showed approximately 2 cm diameter mass accompanied by calcification with some substantial components between the testis and epididymis. Left high testicular resection was performed. The tumor had no continuity between the testis and epididymis, and the spermatic cord transection was negative. Pathological findings showed well differentiated fatty component and a dedifferentiated component around the trabecular bone-like tissue. We observed dedifferentiated dysmorphic cells mixed with fatty droplets of unequal size. Immunostaining led to the diagnosis of dedifferentiated liposarcoma. No additional postoperative therapy was performed. The possibility of dedifferentiated liposarcoma should be kept in mind even if mass is confined to the scrotum and consisted of calcification. In the case of an intrascrotal calcified mass with malignant perspective, radical surgery is highly recommended.

Epidemiological analysis of the patients with psoriasis in Asian countries and region using the same clinical case cards between 2020 and 2022.

Although many epidemiological surveys for patients with psoriasis have been reported based on individual countries or facilities, there has been no study encompassing the major countries or the region in Asia. The Asian Society for Psoriasis (ASP) has been conducting an epidemiological study across various Asian countries and regions to elucidate the and compare the epidemiology of psoriasis. A total of 1948 cases were analyzed, with 938 cases from Japan, 530 cases from China, 325 cases from Korea, 141 cases from Chinese Taipei, and 14 cases from Thailand, all of which were enrolled between 2020 and 2022. In the Asian region total, the male-female ratio was 1.87:1 and the peak age at disease onset was 20-29 years. The proportion of psoriasis vulgaris (PsV), psoriatic arthritis (PsA), and pustular psoriasis (PP) was 80.1%, 17.7%, and 2.2%, respectively, and PsA was more commonly associated with nail symptoms than psoriasis vulgaris (PsV). Of the patients, 13% had a familial history of psoriasis and the most frequently affected family member was the father. Regarding treatment, 78.3% of the patients received topical medications, 9.0% underwent phototherapy, 34.0% received oral medications, and 36.1% were treated with biological agents. This study provided valuable information on the epidemiology and treatment of psoriasis using the registry data collected with the common reporting form in the same period in major Asian countries and regions. Male predominance is a distinctive feature of psoriasis in Asia. This epidemiological data registry in the ASP will continue afterwards.

Association analysis of the HLA-C gene in Japanese alopecia areata.

Alopecia areata (AA) is an organ-specific and cell-mediated autoimmune disease involving hair loss, but its pathogenesis remains poorly understood. Many autoimmune diseases are genetically associated with alleles of the human leukocyte antigen (HLA) genes within the major histocompatibility complex. Associations between AA and HLA genes were previously observed in some different ethnic groups. However, the results were inconsistent, and a primary susceptibility HLA gene and/or region has not yet been assigned for AA. The aim of this study was to evaluate whether an allele of the HLA-C locus, HLA-C*07:04, which was strongly associated with AA in Chinese Hans, could be replicated in the Japanese population. The HLA-C locus was genotyped by the SSO method using 156 AA patients and 560 healthy controls. As a consequence, among the 17 alleles detected, only two alleles, C*04:01 (OR = 2.25, CI 95 % = 1.35-3.75, P = 1.84E-03) and C*15:02 (OR = 2.52, CI 95 % = 1.37-4.64, P = 2.90E-03), were significantly associated with AA after Bonferroni correction. Further, the stratification analysis suggested that C*04:01, C*07:02, and C*15:02 represented different AA genetic risk factors in each sub-phenotype.

IL12B and IL23R gene SNPs in Japanese psoriasis.

Psoriasis is a common human skin disease whereby abnormal production of inflammatory mediators is believed to play an important role in its pathogenesis. The IL12B gene, which encodes the shared IL-12p40 subunit in two cytokines, IL-12 and IL-23, and the IL23R gene, which encodes a subunit of the receptor for IL-23, were identified as psoriasis-susceptibility genetic factors in recent candidate gene and genome-wide association studies of Chinese and Europeans. Since there are significant differences in the incidence of psoriasis between Europeans and Japanese suggesting a genetic ethnic effect, we examined the association of IL12B and IL23R gene polymorphisms with psoriasis in a cohort of Japanese. In this study, we genotyped two SNPs (rs3212227 and rs6887695) in the IL12B gene and one SNP (rs11209026) in the IL23R gene using 560 Japanese psoriasis cases and 560 controls and compared our results with those previously published for Europeans and Asians. Our study showed significant associations between psoriasis and both IL12B gene SNPs, rs3212227 (odds ratio (OR) = 1.35, P = 4.94E-04) and rs6887695 (OR = 1.32, P = 2.00E-03), but no significant association between psoriasis and the IL23R SNP, rs11209026. Furthermore, a significant haplotype association was found for the IL12B gene protective haplotype C-C (OR = 0.71, P = 1.84E-04) in Japanese, as previously elucidated in the studies of European ancestry.

Static FBG strain sensor with high resolution and large dynamic range by dual-comb spectroscopy.

We demonstrate a fiber Bragg grating (FBG) strain sensor with optical frequency combs. To precisely characterize the optical response of the FBG when strain is applied, dual-comb spectroscopy is used. Highly sensitive dual-comb spectroscopy of the FBG enabled strain measurements with a resolution of 34 nε. The optical spectral bandwidth of the measurement exceeds 1 THz. Compared with conventional FBG strain sensor using a continuous-wave laser that requires rather slow frequency scanning with a limited range, the dynamic range and multiplexing capability are significantly improved by using broadband dual-comb spectroscopy.

10-MHz, Yb-fiber chirped-pulse amplifier system with large-scale transmission gratings.

Large-scale transmission gratings were produced for a stretcher and a compressor in the Yb-fiber chirped-pulse amplification system. A 23-W, 200-fs laser system with a 10-MHz repetition rate was demonstrated. Focused intensity as high as 10(14) W/cm(2) was achieved, which is high enough for multi-photon processes such as high-order harmonics generation and multi-photon ionization of neutral atoms. High-order harmonics up to 7th order were observed using Xe gas as a nonlinear medium.

6-GHz, Kerr-lens mode-locked Yb:Lu2O3 ceramic laser for comb-resolved broadband spectroscopy.

A laser diode (LD)-pumped, 6-GHz repetition rate, ytterbium (Yb)-doped Lu2O3 ceramic Kerr-lens mode-locked laser is described. A bow-tie ring cavity enabled the generation of femtosecond pulses centered at a wavelength of 1076 nm with an average power of 10 mW. The pulse duration after an amplifier was 161 fs whereas the transform-limited pulse duration directly from the oscillator was 148 fs. The repetition frequency was sufficiently high for each longitudinal mode to be spectrally resolved by a commercially available optical spectrum analyzer. The developed laser was successfully applied to the absorption spectroscopy of metastable helium4 and demonstrated the suitability of the system as a source for comb-resolved broadband spectroscopy.

Kerr-lens mode-locked Yb:KYW laser at 4.6-GHz repetition rate.

We developed a laser-diode pumped, 4.6-GHz repetition-rate, Yb:KYW Kerr-lens mode-locked femtosecond oscillator. A bow-tie ring cavity generates an output power of 14.6 mW with a spectrum width of 11 nm at 1046 nm. To the best of our knowledge, this is the highest-repetition frequency in the laser-diode pumped femtosecond Kerr-lens mode-locked laser.

Injection locking of Yb-fiber based optical frequency comb.

We demonstrated the synchronization of offset and repetition frequency between two independent Yb-doped fiber mode-locked lasers by injection locking. By injecting master-laser pulse-train into slave laser cavity, stability and accuracy of master frequency comb are transferred to slave comb. Passive stabilization of frequency comb offers robust and convenient way to duplicate frequency comb that can be applied to long-distance comb transfer. Injecting master pulse would also help to initiate and stabilize mode-locking of high repetition rate or ultrabroadband frequency combs. Additionally, we also demonstrated even more robust synchronization of combs can be achieved with the help of active stabilization of relative offset frequency difference.

Vacuum ultraviolet frequency combs generated by a femtosecond enhancement cavity in the visible.

We present the first (to our best knowledge) femtosecond enhancement cavity in the visible wavelength range for ultraviolet frequency comb generation. The cavity is seeded at 518 nm by a frequency-doubled Yb fiber laser and operates at a peak intensity of 1.2×10(13) W/cm(2). High harmonics of up to the ninth order (~57 nm) are generated in an intracavity xenon gas jet. Intracavity high harmonic powers of several milliwatts for the third harmonic order and microwatts for the fifth harmonic order prove the potential of the "green cavity" as an efficient ultraviolet frequency comb source for future spectroscopic experiments. A limiting degradation effect of the cavity mirrors is avoided by operating at a constant oxygen background pressure.

Generalized pustular psoriasis in a child: observation of long-term combination therapy with etretinate and calcipotriol for 16 years.

Generalized pustular psoriasis (GPP) is a rare condition in young children. It is difficult to treat and may require long-term systemic therapy. We report the long-term course of a 3-year-old boy whose onset of psoriasis dated to age 7 months. He was treated with etretinate and psoralen plus ultraviolet A therapy initially and then with etretinate alone, and at age 12, topical calcipotriol was added. At the age of 19, he had been taking oral retinoids for 16 years, with a mean dose of etretinate of 0.22 mg/kg per day, a total amount of approximately 37 g, without evidence of stunted growth, ligamentous calcification, hyperostosis, or hepatic toxicity.

A novel splicing variant of CADM2 as a protective transcript of psoriasis.

CADM2, a candidate gene for psoriasis, was identified by a genome-wide association study using microsatellites in the Japanese population (561 cases and 561 controls). Moreover, haplotype analysis included an additional 68 SNPs and indicated that a 110-kb haplotype block was detected for the protective risk haplotype of psoriasis. We also identified an initial exon of novel splicing variants in this haplotype block. A functional analysis by qRT-PCR using RNAs from the blood of 56 cases and 64 controls significantly demonstrated an inverse correlation between expression frequencies in a novel splicing variant and the number of alleles associated with psoriasis. To confirm these results, we must perform replication studies using other ethnic groups and more functional analysis particularly for skin tissues.

Coherent quasi-cw 153 nm light source at 33 MHz repetition rate.

We present a quasi-cw laser in a vacuum ultraviolet region at megahertz repetition rate. The narrowband pulses generated from an ytterbium-fiber laser system at 33 MHz repetition rate at the central wavelength of 1074 nm are frequency-converted by successive stages of LiB(3)O(5) crystals and KBe(2)BO(3)F(2) crystals. The generated radiation at 153 nm has the shortest wavelength achieved through phase-matched frequency conversion processes in nonlinear optical crystals to our knowledge.