Faculty Profiles - Koji Nishiguchi

Analysis of the aqueous humor before and after the administration of faricimab in patients with nAMD

Ryo Nonogaki, Hikaru Ota, Jun Takeuchi, Yuyako Nakano, Ai Fujita Sajiki, Takahito Todoroki, Koichi Nakamura, Hiroki Kaneko, Koji M. Nishiguchi

Scientific Reports Vol. 14 ( 1 ) page： 31951 2024.12

Assessment of factors affecting anterior chamber depth from data obtained from health checkup participants in Japan

Taiga Inooka, Taro Kominami, Ryo Tomita, Ayana Suzumura, Tsuyoshi Matsuno, Junya Ota, Yoshito Koyanagi, Hideo Takeyama, Shinji Ueno, Yasuki Ito, Koji M. Nishiguchi, Kenya Yuki

Scientific Reports Vol. 14 ( 1 ) page： 30342 2024.12

Genetic Risk Stratification of Primary Open-Angle Glaucoma in Japanese Individuals

Akiyama M., Tamiya G., Fujiwara K., Shiga Y., Yokoyama Y., Hashimoto K., Sato M., Sato K., Narita A., Hashimoto S., Ueda E., Furuta Y., Hata J., Miyake M., Ikeda H.O., Suda K., Numa S., Mori Y., Morino K., Murakami Y., Shimokawa S., Nakamura S., Yawata N., Fujisawa K., Yamana S., Mori K., Ikeda Y., Miyata K., Mori K., Ogino K., Koyanagi Y., Kamatani Y., Matsuda K., Yamanashi Y., Furukawa Y., Morisaki T., Okada Y., Murakami Y., Muto K., Nagai A., Nakamura Y., Obara W., Yamaji K., Takahashi K., Asai S., Takahashi Y., Higashiue S., Kobayashi S., Yamaguchi H., Nagata Y., Wakita S., Nito C., Iwasaki Y.K., Murayama S., Yoshimori K., Miki Y., Obata D., Higashiyama M., Masumoto A., Koga Y., Koretsune Y., Ninomiya T., Sonoda K.H., Nakazawa T., Aihara M., Sakata R., Kashiwagi K., Mabuchi F., Kawase K., Iwata T., Tsujikawa M., Nishiguchi K.M.

Ophthalmology Vol. 131 ( 11 ) page： 1271 - 1280 2024.11

Publisher：Ophthalmology

Purpose: To assess the impact of genetic risk estimation for primary open-angle glaucoma (POAG) in Japanese individuals. Design: Cross-sectional analysis. Participants: Genetic risk scores (GRSs) were constructed based on a genome-wide association study (GWAS) of POAG in Japanese people. A total of 3625 Japanese individuals, including 1191 patients and 2434 controls (Japanese Tohoku), were used for the model selection. We also evaluated the discriminative accuracy of constructed GRSs in a dataset comprising 1034 patients and 1147 controls (the Japan Glaucoma Society Omics Group [JGS-OG] and the Genomic Research Committee of the Japanese Ophthalmological Society [GRC-JOS]) and 1900 participants from a population-based study (Hisayama Study). Methods: We evaluated 2 types of GRSs: polygenic risk scores using the pruning and thresholding procedure and a GRS using variants associated with POAG in the GWAS of the International Glaucoma Genetics Consortium (IGGC). We selected the model with the highest areas under the receiver operating characteristic curve (AUC). In the population-based study, we evaluated the correlations between GRS and ocular measurements. Main Outcome Measure: Proportion of patients with POAG after stratification according to the GRS. Results: We found that a GRS using 98 variants, which showed genome-wide significance in the IGGC, showed the best discriminative accuracy (AUC, 0.65). In the Japanese Tohoku, the proportion of patients with POAG in the top 10% individuals was significantly higher than that in the lowest 10% (odds ratio [OR], 6.15; 95% confidence interval [CI], 4.35–8.71). In the JGS-OG and GRC-JOS, we confirmed similar impact of POAG GRS (AUC, 0.64; OR [top vs. bottom decile], 5.81; 95% CI, 3.79–9.01). In the population-based study, POAG prevalence was significantly higher in the top 20% individuals of the GRS compared with the bottom 20% (9.2% vs. 5.0%). However, the discriminative accuracy was low (AUC, 0.56). The POAG GRS was correlated positively with intraocular pressure (r = 0.08: P = 4.0 × 10–4) and vertical cup-to-disc ratio (r = 0.11; P = 4.0 × 10–6). Conclusions: The GRS showed moderate discriminative accuracy for POAG in the Japanese population. However, risk stratification in the general population showed relatively weak discriminative performance. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

DOI： 10.1016/j.ophtha.2024.05.026

Five-year outcomes of treat and extend regimen using intravitreal aflibercept injection for treatment-naïve age-related macular degeneration

Ota, H; Kataoka, K; Asai, K; Takeuchi, J; Nakano, Y; Nakamura, K; Todoroki, T; Nishiguchi, KM

GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY Vol. 262 ( 11 ) page： 3483 - 3491 2024.11

Language：English Publisher：Graefe's Archive for Clinical and Experimental Ophthalmology

Purpose: This study evaluated the long-term outcomes of eyes with neovascular age-related macular degeneration (nAMD) treated with aflibercept according to a treat-and-extend (T&E) regimen for up to 5 years. Methods This retrospective study included 112 eyes of 111 patients with nAMD who received aflibercept according to the T&E regimen. The patients received 3 monthly injections of aflibercept followed by a T&E regimen for at least 12 months. Data, including best-corrected visual acuity (BCVA), treatment interval, presence of exudation, central retinal thickness, and central choroidal thickness were analyzed. Results: Of the 112 consecutive eyes, 66 completed the 5-year follow-up. After 5 years of treatment, BCVA (logMAR) was significantly better than baseline (0.29 ± 0.31 at baseline and 0.18 ± 0.23 at 5 years, P < 0.01). A mean of 7.0 ± 1.5 injections in the first year and 4.9 ± 2.2 injections per year thereafter were required. In eyes with subretinal hyperreflective material (SHRM) at baseline, BCVA at baseline and 5 years were significantly worse than in eyes without SHRM at baseline and 5 years. However, the eyes with SHRM required fewer injections and exhibited greater BCVA improvement. Conclusion: This retrospective study demonstrated the effectiveness of the T&E regimen with aflibercept in managing nAMD over a 5-year period, maintaining significant improvements in BCVA.

DOI： 10.1007/s00417-024-06519-5

Clinical utility of swept-source optical coherence tomography angiography for the diagnosis of exudative maculopathy

Sajiki, A; Kataoka, K; Takeuchi, J; Ota, H; Nakano, Y; Horiguchi, E; Kaneko, H; Terasaki, H; Ito, Y; Nishiguchi, KM

JAPANESE JOURNAL OF OPHTHALMOLOGY Vol. 68 ( 6 ) page： 614 - 620 2024.11

Language：English Publisher：Japanese Journal of Ophthalmology

Purpose: To assess the feasibility of swept-source optical coherence tomography angiography (SS-OCTA) to differentiate macular diseases, including nonpolypoidal macular neovascularization (MNV), polypoidal choroidal vasculopathy (PCV), type 3 MNV, and chronic central serous chorioretinopathy (CSC) without indocyanine green angiography (ICGA). Study design: Retrospective observational study. Methods: This study examined 63 eyes of 63 patients with treatment-naive neovascular age-related macular degeneration (AMD), including 23 eyes with nonpolypoidal MNV, 17 eyes with PCV, and 1 eye with type 3 MNV and 22 eyes with chronic CSC. Two independent retina specialists, blinded to the clinical diagnosis, assessed each case of neovascular AMD and chronic CSC using only B-scan and en face images of SS-OCTA without referring to other examination outcomes. Results: By SS-OCTA alone, 19 eyes were diagnosed with nonpolypoidal MNV, 17 eyes with PCV, 2 eyes with type 3 MNV, and 22 eyes with chronic CSC, indicating high sensitivity (82.6%, 94.1%, 100%, and 100%, respectively) and specificity (100%, 97.8%, 98.4%, and 100%, respectively); however, three eyes could not be diagnosed because of obscure images. The agreement of diagnosis with SS-OCTA alone was high between the two specialists (κ = 0.82). Conclusion: SS-OCTA showed high sensitivity and specificity in the differentiation of nonpolypoidal MNV, PCV, type 3 MNV, and chronic CSC. The differential criteria based on SS-OCTA could be a substitute for the ICGA-based diagnoses.

DOI： 10.1007/s10384-024-01115-w

Phenotypic variability of RP1-related inherited retinal dystrophy associated with the c.5797 C > T (p.Arg1933*) variant in the Japanese population. International journal

Keigo Natsume, Taro Kominami, Kensuke Goto, Yoshito Koyanagi, Taiga Inooka, Junya Ota, Kenichi Kawano, Kazuhisa Yamada, Daishi Okuda, Kenya Yuki, Koji M Nishiguchi, Hiroaki Ushida

Scientific reports Vol. 14 ( 1 ) page： 25669 - 25669 2024.10

Language：English Publishing type：Research paper (scientific journal)

The phenotypes of RP1-related inherited retinal dystrophies (RP1-IRD), causing autosomal dominant (AD) and autosomal recessive (AR) diseases, vary depending on specific RP1 variants. A common nonsense mutation near the C-terminus, c.5797 C > T (p.Arg1933*), is associated with RP1-IRD, but the exact role of this mutation in genotype-phenotype correlation remains unclear. In this study, we retrospectively analyzed patients with RP1-IRD (N = 42) from a single center in Japan. AR RP1-IRD patients with the c.5797 C > T mutation (N = 14) mostly displayed macular dystrophy but rarely retinitis pigmentosa or cone-rod dystrophy. Conversely, AR RP1-IRD patients without the c.5797 C > T mutation, including those with other pathogenic RP1 variants, were mostly diagnosed with severe retinitis pigmentosa. Full-field electroretinograms were significantly better in patients homozygous or compound heterozygous for the c.5797 C > T mutation than in those without this mutation, corresponding to their milder phenotypes. Clinical tests also revealed a slower onset of age and a better mean deviation value with the static visual field in AR RP1-IRD patients with the c.5797 C > T mutation compared to those without. Therefore, the presence of c.5797 C > T may partly account for the phenotypic variety of RP1-IRD and may yield milder phenotypes. These findings may be useful for predicting the prognosis of RP1-IRD patients.

DOI： 10.1038/s41598-024-77441-3

A Novel Approach To Predict Glaucomatous Impairment in the Central 10° Visual Field, Excluding the Effect of Cataract

今月の表紙網膜色素変性患者の前房内水晶体脱臼

前原紘基, 西口康二

臨床眼科 Vol. 78 ( 10 ) page： 1186 - 1186 2024.10

Tomita, R; Asaoka, R; Hirasawa, K; Fujino, Y; Omura, T; Inatomi, T; Obana, A; Nishiguchi, KM; Tanito, M

TRANSLATIONAL VISION SCIENCE & TECHNOLOGY Vol. 13 ( 10 ) page： 35 2024.10

Language：English Publisher：Translational Vision Science and Technology

Purpose: Our previous study predicted genuine glaucomatous visual field (VF) impairment in the central 10° VF, excluding the effect of cataract, using visual acuity (VA) and global indexes of VF more accurately than pattern deviation (PD). This study aimed to improve the accuracy by using pointwise total deviation (TD) values with the machine-learning method of random forest model (RFM) and to investigate whether incorporating optical coherence tomography–measured ganglion cell-inner plexiform layer (GCIPL) thickness is useful. Methods: This retrospective study included 89 eyes with open-angle glaucoma that underwent successful cataract surgery (with or without iStent implantation or ab interno trabeculotomy). Postoperative TD in each of the 68 VF points was predicted using preoperative (1) PD, (2) VA and VF with a linear regression model (LM), and (3) VA and VF with RFM, and averaged as predicted mean TD (mTDpost). Further prediction was made by incorporating the preoperative GCIPL into the best model. Results: The mean absolute error (MAE) between the actual and predicted mTDpost with RFM (1.25 ± 1.03 dB) was significantly smaller than that with PD (3.20 ± 4.06 dB, p < 0.01) and LM (1.42 ± 1.06 dB, p < 0.05). The MAEs with the model incorporating GCIPL into RFM (1.24 ± 1.04 dB) and RFM were not significantly different. Conclusions: Accurate prediction of genuine glaucomatous VF impairment was achieved using pointwise TD with RFM. No merit was observed by incorporating the GCIPL into this model. Translational Relevance: This pointwise RFM could clinically reduce cataract effect on VF.

DOI： 10.1167/tvst.13.10.35

GENETIC ETIOLOGY AND CLINICAL FEATURES OF ACHROMATOPSIA IN JAPAN. International journal

Taiga Inooka, Takaaki Hayashi, Kazushige Tsunoda, Kazuki Kuniyoshi, Hiroyuki Kondo, Kei Mizobuchi, Akiko Suga, Takeshi Iwata, Kazutoshi Yoshitake, Mineo Kondo, Kensuke Goto, Junya Ota, Taro Kominami, Koji M Nishiguchi, Shinji Ueno

Retina (Philadelphia, Pa.) Vol. 44 ( 10 ) page： 1836 - 1844 2024.10

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: To ascertain the characteristics of achromatopsia (ACHM) in Japan by analyzing the genetic and phenotypic features of patients with ACHM. METHODS: The medical records of 52 patients from 47 Japanese families who were clinically diagnosed with ACHM were reviewed in this retrospective observational study. RESULTS: Thirty-six causative variants of ACHM were identified in 26 families via whole-exome sequencing: PDE6C (12 families), CNGA3 (10 families), CNGB3 (two families), and GNAT2 (two families). However, none of the 6 causative variants that are known to cause ACHM, or the 275 other genes listed in RetNet, were observed in 19 families. A significant trend toward older age and worsening of ellipsoid zone disruption on optical coherence tomography images was observed (P < 0.01). Progressive ellipsoid zone disruptions were observed in 13 eyes of seven patients during the follow-up visits. These patients harbored one or more variants in PDE6C. CONCLUSION: The ACHM phenotype observed in this study was similar to those observed in previous reports; however, the causative gene variants differed from those in Europe. The low identification ratio of causative genes in whole-exome sequencing suggests the presence of unique hotspots in Japanese patients with ACHM that were not detectable via ordinal whole-exome sequencing.

DOI： 10.1097/IAE.0000000000004170

Visualization of distribution in the vitreous cavity via eye drops using ultra-heavily T2-weighted sequences in MRI: a preliminary study with enucleated pig eyes

Kato, Y; Yuki, K; Nishiguchi, K; Naganawa, S

RADIOLOGICAL PHYSICS AND TECHNOLOGY Vol. 17 ( 3 ) page： 715 - 724 2024.9

Language：English Publisher：Radiological Physics and Technology

We investigated whether magnetic resonance imaging can visualize the distribution in the vitreous cavity via eye drops of ophthalmic solutions, gadolinium-based contrast agent, and 17O-water, and to clarify the usefulness of ultra-heavily T2-weighted sequences in the research of intraocular distribution. Five different solutions (V-ROHTO, TRAVATANZ, gadobutrol, H217O, and saline) were administered to excised pig eye specimens. The samples were scanned using T1 mapping, T2 mapping, 3D T2-weighted (echo times (TE): 500, 3200, and 4500 ms), a half-Fourier single-shot turbo-spin echo sequence (HASTE; TE: 440 and 3000 ms), and 3D-real inversion-recovery before eye drops administration. Subsequently, we used a plastic dropper to drop a 0.5 mL solution each, and images were obtained up to 26 h later. Temporal changes in the T1 and T2 values of the anterior chamber and vitreous cavity were compared. The other sequences were evaluated by determining temporal signal changes as signal intensity ratio (SIR) compared to “No drop.” The T1 and T2 values of samples treated with gadobutrol and H217O decreased over time. The SIR of samples treated with gadobutrol and H217O showed remarkable changes in the 3D T2-weighted images, whereas no remarkable temporal changes were observed in the other solutions. Longer TEs resulted in remarkable changes. We demonstrated that visualization of distribution in the vitreous cavity via eye drops could be achieved with excised pig eyes using gadobutrol and H217O, but not with ophthalmic solutions. Ultra-heavily T2-weighted sequences may be promising for the early and highly sensitive visualization of the intraocular distribution of eye drops.

DOI： 10.1007/s12194-024-00826-6

Aqueous Humor Cytokine Analysis in Age-Related Macular Degeneration After Switching From Aflibercept to Faricimab

Takahito Todoroki, Jun Takeuchi, Hikaru Ota, Yuyako Nakano, Ai Fujita Sajiki, Koichi Nakamura, Hiroki Kaneko, Koji M. Nishiguchi

Investigative Ophthalmology & Visual Science Vol. 65 ( 11 ) page： 15 - 15 2024.9

本邦における杆体一色覚の遺伝的病因と臨床的特徴

井岡大河, 林孝彰, 溝渕圭, 角田和繁, 國吉一樹, 近藤寛之, 太田淳也, 後藤健介, 小南太郎, 西口康二, 上野真治

眼科臨床紀要 Vol. 17 ( 8 ) page： 635 - 635 2024.8

Specification of variant interpretation guidelines for inherited retinal dystrophy in Japan.

Kaoru Fujinami, Koji M Nishiguchi, Akio Oishi, Masato Akiyama, Yasuhiro Ikeda

Japanese journal of ophthalmology Vol. 68 ( 4 ) page： 389 - 399 2024.7

Language：English

Accurate interpretation of sequence variants in inherited retinal dystrophy (IRD) is vital given the significant genetic heterogeneity observed in this disorder. To achieve consistent and accurate diagnoses, establishment of standardized guidelines for variant interpretation is essential. The American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines for variant interpretation serve as the global "cross-disease" standard for classifying variants in Mendelian hereditary disorders. These guidelines propose a systematic approach for categorizing variants into 5 classes based on various types of evidence, such as population data, computational data, functional data, and segregation data. However, for clinical genetic diagnosis and to ensure standardized diagnosis and treatment criteria, additional specifications based on features associated with each disorder are necessary. In this context, we present a comprehensive framework outlining the newly specified ACMG/AMP rules tailored explicitly to IRD in the Japanese population on behalf of the Research Group on Rare and Intractable Diseases (Ministry of Health, Labour and Welfare of Japan). These guidelines consider disease frequencies, allele frequencies, and both the phenotypic and the genotypic characteristics unique to IRD in the Japanese population. Adjustments and modifications have been incorporated to reflect the specific requirements of the population. By incorporating these IRD-specific factors and refining the existing ACMG/AMP guidelines, we aim to enhance the accuracy and consistency of variant interpretation in IRD cases, particularly in the Japanese population. These guidelines serve as a valuable resource for ophthalmologists and clinical geneticists involved in the diagnosis and treatment of IRD, providing them with a standardized framework to assess and classify genetic variants.

DOI： 10.1007/s10384-024-01063-5

Mice with deficiency in <i>Pcdh15</i>, a gene associated with bipolar disorders, exhibit significantly elevated diurnal amplitudes of locomotion and body temperature

特集第77回日本臨床眼科学会講演集[4] 原著 HLA-A26陽性ベーチェット病との鑑別に苦慮した真菌性眼内炎の1例

新美渚, 井岡大河, 鈴村文那, 牛田宏昭, 西口康二

臨床眼科 Vol. 78 ( 6 ) page： 716 - 721 2024.6

Mori, D; Inami, C; Ikeda, R; Sawahata, M; Urata, S; Yamaguchi, ST; Kobayashi, Y; Fujita, K; Arioka, Y; Okumura, H; Kushima, I; Kodama, A; Suzuki, T; Hirao, T; Yoshimi, A; Sobue, A; Ito, T; Noda, Y; Mizoguchi, H; Nagai, T; Kaibuchi, K; Okabe, S; Nishiguchi, K; Kume, K; Yamada, K; Ozaki, N

TRANSLATIONAL PSYCHIATRY Vol. 14 ( 1 ) page： 216 2024.5

Language：English Publisher：Translational Psychiatry

Genetic factors significantly affect the pathogenesis of psychiatric disorders. However, the specific pathogenic mechanisms underlying these effects are not fully understood. Recent extensive genomic studies have implicated the protocadherin-related 15 (PCDH15) gene in the onset of psychiatric disorders, such as bipolar disorder (BD). To further investigate the pathogenesis of these psychiatric disorders, we developed a mouse model lacking Pcdh15. Notably, although PCDH15 is primarily identified as the causative gene of Usher syndrome, which presents with visual and auditory impairments, our mice with Pcdh15 homozygous deletion (Pcdh15-null) did not exhibit observable structural abnormalities in either the retina or the inner ear. The Pcdh15-null mice showed very high levels of spontaneous motor activity which was too disturbed to perform standard behavioral testing. However, the Pcdh15 heterozygous deletion mice (Pcdh15-het) exhibited enhanced spontaneous locomotor activity, reduced prepulse inhibition, and diminished cliff avoidance behavior. These observations agreed with the symptoms observed in patients with various psychiatric disorders and several mouse models of psychiatric diseases. Specifically, the hyperactivity may mirror the manic episodes in BD. To obtain a more physiological, long-term quantification of the hyperactive phenotype, we implanted nano tag® sensor chips in the animals, to enable the continuous monitoring of both activity and body temperature. During the light-off period, Pcdh15-null exhibited elevated activity and body temperature compared with wild-type (WT) mice. However, we observed a decreased body temperature during the light-on period. Comprehensive brain activity was visualized using c-Fos mapping, which was assessed during the activity and temperature peak and trough. There was a stark contrast between the distribution of c-Fos expression in Pcdh15-null and WT brains during both the light-on and light-off periods. These results provide valuable insights into the neural basis of the behavioral and thermal characteristics of Pcdh15-deletion mice. Therefore, Pcdh15-deletion mice can be a novel model for BD with mania and other psychiatric disorders, with a strong genetic component that satisfies both construct and surface validity.

DOI： 10.1038/s41398-024-02952-6

Decrease in electrolyte after vitrectomy surgery may affect the results of forensic investigations using vitreous humor

Hiroaki Ushida, Ayana Suzumura, Kazuhisa Yamada, Hideyuki Shimizu, Atsuo Suzuki, Yusuke Ishikawa, Ryosuke Kikuchi, Koji M. Nishiguchi, Hiroki Kaneko

BMC Ophthalmology Vol. 24 ( 1 ) page： 219 2024.5

Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media LLC

Abstract

Purpose

Vitreous humor (VH) is used for postmortem biochemical studies because it is well protected in an uncontaminated state even after death. The goal of this research was to investigate electrolyte concentrations in the VH from human eyes with and without a history of vitrectomy surgery.

Methods

We analyzed the sodium (Na), potassium (K), chloride (Cl) and magnesium (Mg) concentrations from 34 VH samples from 34 patients. Eleven samples were from eyes with a history of vitrectomy, and the remaining 23 eyes had no history of vitrectomy. The correlations of Na, K, Cl and Mg concentrations with patient age, interval between first and second vitrectomy, and lens status (history of cataract surgery) were also evaluated.

Results

The Na, K, Cl and Mg concentrations in VH from vitrectomized eyes were 134.1 ± 7.9 mmol/L, 3.7 ± 0.2 mmol/L, 99.7 ± 6.7 mmol/L and 0.59 ± 0.09 mmol/L, respectively; all were significantly lower than the corresponding concentrations in VH from control eyes (lower by 5.0%, 11.0%, 11.7%, and 22.6%, respectively). Na, K, Cl and Mg concentrations in VH from vitrectomized eyes did not show significant correlations with patient ages or the interval between their first and second vitrectomies. There were no significant differences in Na, K, Cl and Mg concentrations in VH between phakic eyes and intraocular lens-implanted eyes.

Conclusions

With the increasing number of vitrectomies being performed, it is necessary to consider the history of vitrectomy when using a subject’s VH in forensic examination.

DOI： 10.1186/s12886-024-03445-2

Eulerian finite volume method using Lagrangian markers with reference map for incompressible fluid-structure interaction problems

Other Link： https://link.springer.com/article/10.1186/s12886-024-03445-2/fulltext.html

Nishiguchi, K; Shimada, T; Peco, C; Kondo, K; Okazawa, S; Tsubokura, M

COMPUTERS & FLUIDS Vol. 274 2024.4

Publisher：Computers and Fluids

We propose a monolithic fluid–structure interaction (FSI) method that presents the advantages of both the reference map technique (RMT) and the Lagrangian Markers approach on a unified, cell-centered finite volume Eulerian framework. Full Eulerian methods that use a Cartesian mesh are attractive for FSI problems that require large-scale computing and involve complex geometries and large solid deformations. However, conventional full Eulerian methods use the velocity gradient to evaluate solid deformations, hence they suffer from numerical instability caused by the discontinuity of the velocity gradient near the interface. In this work, we develop a novel algorithm that interpolates and transfers a reference mapping information field between a collection of Lagrangian Markers and a Eulerian finite volume framework. As a result of integrating these approaches, our method is able to (1) evaluate solid deformations without computing the velocity gradient in the Eulerian framework thanks to RMT, and (2) remove the numerical dissipation of interfaces and internal variables caused by advection in the full Eulerian RMT, thanks to the use of the Lagrangian Markers to compute the constitutive equations. We illustrate with numerical examples that the proposed method preserves geometrical features and yields more accurate results for the deformation and energy than conventional Eulerian FSI method and the full Eulerian RMT.

DOI： 10.1016/j.compfluid.2024.106210

Detection of elusive DNA copy-number variations in hereditary disease and cancer through the use of noncoding and off-target sequencing reads.

特集第77回日本臨床眼科学会講演集[2] 原著病初期より視神経炎を認めた再発性多発軟骨炎の1例

牛田知子, 牛田宏昭, 夏目啓吾, 鈴村文那, 西口康二

臨床眼科 Vol. 78 ( 4 ) page： 505 - 510 2024.4

Quinodoz M, Kaminska K, Cancellieri F, Han JH, Peter VG, Celik E, Janeschitz-Kriegl L, Schärer N, Hauenstein D, György B, Calzetti G, Hahaut V, Custódio S, Sousa AC, Wada Y, Murakami Y, Fernández AA, Hernández CR, Minguez P, Ayuso C, Nishiguchi KM, Santos C, Santos LC, Tran VH, Vaclavik V, Scholl HPN, Rivolta C

American journal of human genetics Vol. 111 ( 4 ) page： 701 - 713 2024.4

Language：English Publisher：American Journal of Human Genetics

Copy-number variants (CNVs) play a substantial role in the molecular pathogenesis of hereditary disease and cancer, as well as in normal human interindividual variation. However, they are still rather difficult to identify in mainstream sequencing projects, especially involving exome sequencing, because they often occur in DNA regions that are not targeted for analysis. To overcome this problem, we developed OFF-PEAK, a user-friendly CNV detection tool that builds on a denoising approach and the use of “off-target” DNA reads, which are usually discarded by sequencing pipelines. We benchmarked OFF-PEAK on data from targeted sequencing of 96 cancer samples, as well as 130 exomes of individuals with inherited retinal disease from three different populations. For both sets of data, OFF-PEAK demonstrated excellent performance (>95% sensitivity and >80% specificity vs. experimental validation) in detecting CNVs from in silico data alone, indicating its immediate applicability to molecular diagnosis and genetic research.

DOI： 10.1016/j.ajhg.2024.03.001