Faculty Profiles - MARUYAMA Kazuaki

Papers - MARUYAMA Kazuaki

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Phase separation-induced glass transition under critical miscible conditions

Watanabe, M; Shi, D; Kiyama, R; Maruyama, K; Nishizawa, Y; Uchihashi, T; Gong, JP; Nonoyama, T

MATERIALS ADVANCES Vol. 5 ( 18 ) page： 7140 - 7146 2024.9

Publisher：Materials Advances

Plasticizers have been widely utilized to adjust the glass transition temperature (Tg) of glassy polymeric materials. To optimize performance while minimizing volume, plasticizers with a strong affinity for the target polymer are typically chosen. If we consider a combination of a glassy polymer and a plasticizer with a critical miscibility condition, where the miscible/immiscible states are altered by changing the temperature, phase separation induced by temperature variations will trigger the glass transition. In this study, we report on a polymeric material synthesized from a blend of a high Tg polymer and a plasticizer, exhibiting a phase separation-induced glass transition around the upper critical solution temperature (UCST). It is expected from a crossover point of the Tg curve and the demixing curve in a thermodynamic phase diagram, corresponding to the Berghmann point. Poly(isobornyl acrylate) (PIBXA) with an original Tg of ∼100 °C and triethyl phosphate (TEP) were employed as the glassy polymer and plasticizer, respectively. When the TEP fraction was relatively small (∼10 wt%), the sample showed no phase separation and a decrease in Tg compared to that of the pristine PIBXA, following the conventional trend of plasticizer addition. Conversely, at 20 wt% or higher fractions, the samples displayed UCST-type phase separation and an abnormal increase in Tg with increasing plasticizer content. Furthermore, this miscible/immiscible transition can be predicted through an analysis of the temperature-corrected Hansen solubility parameter (HSP). This report proposes a novel role for plasticizers in adjusting Tg and prediction of objective combinations that satisfy the critical miscible condition.

DOI： 10.1039/d4ma00737a

Comfort distance between patients and pharmacists during medication instruction: A prospective observational study at a cancer chemotherapy center

Gocho S., Miyagi Y., Nakayama C., Miyachi Y., Okada S., Maruyama K., Oshima T.

Neuropsychopharmacology Reports 2024

Publisher：Neuropsychopharmacology Reports

Background: The distance from the patient is a crucial factor in the communication with patients. The distance between patients and pharmacists varies depending on several factors. In this study, we aimed to investigate the relationship between comfort distance and patients' physical condition and mood by measuring this distance at a chemotherapy center. Methods: A total of 114 patients were surveyed regarding their physical condition and mood. The distance at which the patients were best able to talk to the pharmacists was measured. For comfort distance measurement, the pharmacists were instructed to approach or move away from the patients. Results: The correlation between physical condition, mood, and comfort distance was examined in both male and female patients, and no significant correlation was found; however, there was a strong correlation between physical condition and mood in female patients. We looked at correlations by further dividing patients into those over and under 65 years of age and found a slight correlation with comfort distance in women under 65. They tended to shorten the distance when they felt well and lengthen the distance when they felt not well. Conclusions: No correlation was found between physical condition or mood and comfort distance in male or female. A slight correlation was observed when age was included; however, the results were not satisfactory. By directly measuring the distance in actual patients, we obtained an actual measurement of the comfort distance that synthesized the patient's condition and various backgrounds during chemotherapy, providing a foothold for future studies.

DOI： 10.1002/npr2.12475

Adipose-Derived Mesenchymal Stem Cells Attenuate Immune Reactions Against Pig Decellularized Bronchi Engrafted into Rat Tracheal Defects

Hisanaga, M; Tsuchiya, T; Watanabe, H; Shimoyama, K; Iwatake, M; Tanoue, Y; Maruyama, K; Yukawa, H; Sato, K; Kato, Y; Matsumoto, K; Miyazaki, T; Doi, R; Tomoshige, K; Nagayasu, T

ORGANOGENESIS Vol. 19 ( 1 ) page： 2212582 2023.12

Language：English Publisher：Organogenesis

Decellularized scaffolds are promising biomaterials for tissue and organ reconstruction; however, strategies to effectively suppress the host immune responses toward these implants, particularly those without chemical crosslinking, remain warranted. Administration of mesenchymal stem cells is effective against immune-mediated inflammatory disorders. Herein, we investigated the effect of isogeneic abdominal adipose-derived mesenchymal stem/stromal cells (ADMSCs) on xenogeneic biomaterial-induced immunoreactions. Peripheral bronchi from pigs, decellularized using a detergent enzymatic method, were engrafted onto tracheal defects of Brown Norway (BN) rats. BN rats were implanted with native pig bronchi (Xenograft group), decellularized pig bronchi (Decellularized Xenograft), or Decellularized Xenograft and ADMSCs (Decellularized Xenograft+ADMSC group). In the latter group, ADMSCs were injected intravenously immediately post implantation. Harvested graft implants were assessed histologically and immunohistochemically. We found that acute rejections were milder in the Decellularized Xenograft and Decellularized Xenograft+ADMSC groups than in the Xenograft group. Mild inflammatory cell infiltration and reduced collagen deposition were observed in the Decellularized Xenograft+ADMSC group. Additionally, ADMSC administration decreased CD8+ lymphocyte counts but increased CD163+ cell counts. In the Decellularized Xenograft+ADMSC group, serum levels of vascular endothelial growth factor and IL-10 were elevated and tissue deposition of IgM and IgG was low. The significant immunosuppressive effects of ADMSCs illustrate their potential use as immunosuppressive agents for xenogeneic biomaterial-based implants.

DOI： 10.1080/15476278.2023.2212582

Electric shock causes a fleeing-like persistent behavioral response in the nematode Caenorhabditis elegans

Tee L.F., Young J.J., Maruyama K., Kimura S., Suzuki R., Endo Y., Kimura K.D.

Genetics Vol. 225 ( 2 ) 2023.10

Publisher：Genetics

Behavioral persistency reflects internal brain states, which are the foundations of multiple brain functions. However, experimental paradigms enabling genetic analyses of behavioral persistency and its associated brain functions have been limited. Here, we report novel persistent behavioral responses caused by electric stimuli in the nematode Caenorhabditis elegans. When the animals on bacterial food are stimulated by alternating current, their movement speed suddenly increases 2- to 3-fold, persisting for more than 1 minute even after a 5-second stimulation. Genetic analyses reveal that voltage-gated channels in the neurons are required for the response, possibly as the sensors, and neuropeptide signaling regulates the duration of the persistent response. Additional behavioral analyses implicate that the animal's response to electric shock is scalable and has a negative valence. These properties, along with persistence, have been recently regarded as essential features of emotion, suggesting that C. elegans response to electric shock may reflect a form of emotion, akin to fear.

DOI： 10.1093/genetics/iyad148

Reading impairment after neonatal hypoglycemia with parieto-temporo-occipital injury without cortical blindness: A case report Open Access

Kurahashi, N; Ogaya, S; Maki, Y; Nonobe, N; Kumai, S; Hosokawa, Y; Ogawa, C; Yamada, K; Maruyama, K; Miura, K; Nakamura, M

WORLD JOURNAL OF CLINICAL CASES Vol. 11 ( 16 ) page： 3899 - 3906 2023.6

<i>MORE</i><i> PANICLES</i> 3, a natural allele of<i> OsTB1/FC1,</i> impacts rice yield in paddy fields at elevated CO<sub>2</sub> levels

Takai, T; Taniguchi, Y; Takahashi, M; Nagasaki, H; Yamamoto, E; Hirose, S; Hara, N; Akashi, H; Ito, J; Arai-Sanoh, Y; Hori, K; Fukuoka, S; Sakai, H; Tokida, T; Usui, Y; Nakamura, H; Kawamura, K; Asai, H; Ishizaki, T; Maruyama, K; Mochida, K; Kobayashi, N; Kondo, M; Tsuji, H; Tsujimoto, Y; Hasegawa, T; Uga, Y

PLANT JOURNAL Vol. 114 ( 4 ) page： 729 - 742 2023.5

Language：English Publisher：Plant Journal

Improving crop yield potential through an enhanced response to rising atmospheric CO2 levels is an effective strategy for sustainable crop production in the face of climate change. Large-sized panicles (containing many spikelets per panicle) have been a recent ideal plant architecture (IPA) for high-yield rice breeding. However, few breeding programs have proposed an IPA under the projected climate change. Here, we demonstrate through the cloning of the rice (Oryza sativa) quantitative trait locus for MORE PANICLES 3 (MP3) that the improvement in panicle number increases grain yield at elevated atmospheric CO2 levels. MP3 is a natural allele of OsTB1/FC1, previously reported as a negative regulator of tiller bud outgrowth. The temperate japonica allele advanced the developmental process in axillary buds, moderately promoted tillering, and increased the panicle number without negative effects on the panicle size or culm thickness in a high-yielding indica cultivar with large-sized panicles. The MP3 allele, containing three exonic polymorphisms, was observed in most accessions in the temperate japonica subgroups but was rarely observed in the indica subgroup. No selective sweep at MP3 in either the temperate japonica or indica subgroups suggested that MP3 has not been involved and utilized in artificial selection during domestication or breeding. A free-air CO2 enrichment experiment revealed a clear increase of grain yield associated with the temperate japonica allele at elevated atmospheric CO2 levels. Our findings show that the moderately increased panicle number combined with large-sized panicles using MP3 could be a novel IPA and contribute to an increase in rice production under climate change with rising atmospheric CO2 levels.

DOI： 10.1111/tpj.16143

A Monolayer MoS<sub>2</sub> FET with an EOT of 1.1 nm Achieved by the Direct Formation of a High-κ Er<sub>2</sub>O<sub>3</sub> Insulator Through Thermal Evaporation

Uchiyama, H; Maruyama, K; Chen, ED; Nishimura, T; Nagashio, K

SMALL Vol. 19 ( 15 ) page： e2207394 2023.4

Language：English Publisher：Small

Achieving the direct growth of an ultrathin gate insulator with high uniformity and high quality on monolayer transition metal dichalcogenides (TMDCs) remains a challenge due to the chemically inert surface of TMDCs. Although the main solution for this challenge is utilizing buffer layers before oxide is deposited on the atomic layer, this method drastically degrades the total capacitance of the gate stack. In this work, we constructed a novel direct high-κ Er2O3 deposition system based on thermal evaporation in a differential-pressure-type chamber. A uniform Er2O3 layer with an equivalent oxide thickness of 1.1 nm was achieved as the gate insulator for top-gated MoS2 field-effect transistors (FETs). The top gate Er2O3 insulator without the buffer layer on MoS2 exhibited a high dielectric constant that reached 18.0, which is comparable to that of bulk Er2O3 and is the highest among thin insulators (< 10 nm) on TMDCs to date. Furthermore, the Er2O3/MoS2 interface (Dit ≈ 6 × 1011 cm−2 eV−1) is confirmed to be clean and is comparable with that of the h-BN/MoS2 heterostructure. These results prove that high-quality dielectric properties with retained interface quality can be achieved by this novel deposition technique, facilitating the future development of 2D electronics.

DOI： 10.1002/smll.202207394

Clinical Factors Associated with Severity of Colonic Diverticular Bleeding and Impact of Bleeding Site

Amano H., Yamamoto T., Ikusaka K., Aoki N., Sakurai M., Honda T., Maruyama K., Aoyagi H., Isono A., Abe K., Asaoka Y., Kodashima S., Tanaka A.

Journal of Clinical Medicine Vol. 12 ( 5 ) 2023.3

Publisher：Journal of Clinical Medicine

Factors associated with serious colonic diverticular bleeding (CDB) are unclear, although the incidence of CDB has increased. We carried out this study to clarify factors associated with serious CDB and rebleeding. Subjects included 329 consecutive patients hospitalized for confirmed or suspected CDB between 2004 and 2021. Patients were surveyed regarding backgrounds, treatment, and clinical course. Of 152 with confirmed CDB, 112 showed bleeding from the right colon, and 40 did from the left colon. Patients received red blood cell transfusions in 157 (47.7%), interventional radiology in 13 (4.0%), and surgery in 6 (1.8%) cases. Early rebleeding within one month occurred in 75 (22.8%) patients, and late rebleeding within one year occurred in 62 (18.8%). Factors associated with red blood cell transfusion included confirmed CDB, anticoagulants, and high shock index. The only factor related to interventional radiology or surgery was confirmed CDB, which was also associated with early rebleeding. Late rebleeding was associated with hypertension, chronic kidney disease and past CDB. Right CDB showed higher rates of transfusion and invasive treatment than left CDB. Confirmed CDB had high frequencies of transfusion, invasive treatment, and early rebleeding. Right CDB seemed to be a risk for serious disease. Factors related to late rebleeding were different from those related to early rebleeding of CDB.

DOI： 10.3390/jcm12051826

An Enhanced Distributed Algorithm for Area Skyline Computation Based on Apache Spark

Li C., Cao Y., Zhu Y., Zhang J., Annisa A., Cheng D., Tang H., Jiang S., Maruyama K., Morimoto Y.

Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) Vol. 14120 LNAI page： 35 - 43 2023

Publisher：Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)

Skyline computations are a way of finding the best data points based on multiple criteria for location-based decision-making. However, as the input data grows larger, these computations become slower and more challenging. To address this issue, we propose an efficient algorithm that uses Apache Spark, a platform for distributed processing, to perform area skyline computations faster and more salable. Our algorithm consists of three main phases: calculating distances between data points, generating distance tuples, and computing the skyline. In the second phase, we apply a technique called local partial skyline extraction, which reduces the amount of data that needs to be sent from each executor (a parallel processing unit) to the driver (a central processing unit). The driver then computes the final skyline from the received data and creates filters to eliminate irrelevant points. Our experiments show that our algorithm can significantly reduce the data size and the computation time of the area skyline.

DOI： 10.1007/978-3-031-40292-0_4

医学の専門分化はどのように起こり、進んできたのか : George Weisz., 2006, Divide and Conquerにおける議論を中心に Open Access

丸山和昭

名古屋大学大学院教育発達科学研究科紀要 Vol. 70 page： 1 - 10 2023

Do heel-unloading orthoses improve clinical outcomes in patients after surgical treatment of calcaneal fracture? A propensity-matched, multicenter analysis of the TRON database

Kagami, Y; Tokutake, K; Takegami, Y; Okui, N; Sakai, T; Inoue, H; Kanemura, T; Hanabayashi, M; Ito, O; Kanayama, Y; Maruyama, K; Yoshida, H; Ando, T; Sugimoto, R; Sugimoto, T; Imagama, S

PROSTHETICS AND ORTHOTICS INTERNATIONAL Vol. 46 ( 6 ) page： 569 - 575 2022.12

Language：English Publisher：Prosthetics and Orthotics International

Background:Postoperative protocols after surgical treatment of calcaneal fracture have not been standardized to date. There are only a few reports on the efficacy of heel-unloading orthoses (HUOs; Mars shoe, Graffin orthosis), and thier efficacy is uncertain.Objectives:The purpose of this study was to compare postoperative radiologic and clinical outcomes in patients with calcaneal fractures who used Graffin orthosis.Study design:Multicenter retrospective study.Methods:We finally extracted 182 patients from a database of the Trauma Research Group of Nagoya and divided them into two groups: group C (underwent casting or splinting only) and group O (Graffin orthosis was used). A propensity score algorithm was used to match group C to group O in a 1:1 ratio. We evaluated American Orthopaedic Foot and Ankle Society (AOFAS) score at three and six months after surgery and at final follow-up. Differences in reduction of the Böhler angle between the two groups were evaluated radiographically. All data were analyzed with a t-Test or Fisher's exact test. P <.05 was considered statistically significant.Results:The AOFAS score 3 months after surgery in group O was significantly higher than that in group C (69.57 vs. 77.22; P =.004). However, there were no statistically significant differences between group C vs. group O in AOFAS scores at 6 months after surgery and at final follow-up (81.92 vs. 85.67 and 89.18 vs. 88.13; P =.087 and 0.597, respectively). There was no significant statistical difference in the reduction of the Böhler angle (5.07 vs. 5.89; P =.529).Conclusions:At 3 months postoperatively, the orthosis group showed predominantly better functional results. We believe that heel-unloading orthoses are useful for patients who require an early return to work and to daily life.

DOI： 10.1097/PXR.0000000000000168

CRISPR-mediated Bmpr2 point mutation exacerbates late pulmonary vasculopathy and reduces survival in rats with experimental pulmonary hypertension

Kabwe J.C., Sawada H., Mitani Y., Oshita H., Tsuboya N., Zhang E., Maruyama J., Miyasaka Y., Ko H., Oya K., Ito H., Yodoya N., Otsuki S., Ohashi H., Okamoto R., Dohi K., Nishimura Y., Mashimo T., Hirayama M., Maruyama K.

Respiratory Research Vol. 23 ( 1 ) 2022.12

Publisher：Respiratory Research

Background: Patients with pulmonary arterial hypertension (PAH) carrying bone morphogenetic protein receptor type 2 (Bmpr2) mutations present earlier with severe hemodynamic compromise and have poorer survival outcomes than those without mutation. The mechanism underlying the worsening clinical phenotype of PAH with Bmpr2 mutations has been largely unaddressed in rat models of pulmonary hypertension (PH) because of the difficulty in reproducing progressive PH in mice and genetic modification in rats. We tested whether a clinically-relevant Bmpr2 mutation affects the progressive features of monocrotaline (MCT) induced-PH in rats. Methods: A monoallelic single nucleotide insertion in exon 1 of Bmpr2 (+/44insG) was generated in rats using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9, then PH, pulmonary vascular disease (PVD) and survival after MCT injection with or without a phosphodiesterase type 5 inhibitor, tadalafil, administration were assessed. Results: The +/44insG rats had reduced BMPR2 signalling in the lungs compared with wild-type. PH and PVD assessed at 3-weeks after MCT injection were similar in wild-type and +/44insG rats. However, survival at 4-weeks after MCT injection was significantly reduced in +/44insG rats. Among the rats surviving at 4-weeks after MCT administration, +/44insG rats had increased weight ratio of right ventricle to left ventricle plus septum (RV/[LV + S]) and % medial wall thickness (MWT) in pulmonary arteries (PAs). Immunohistochemical analysis showed increased vessels with Ki67-positive cells in the lungs, decreased mature and increased immature smooth muscle cell phenotype markers in the PAs in +/44insG rats compared with wild-type at 3-weeks after MCT injection. Contraction of PA in response to prostaglandin-F2α and endothelin-1 were significantly reduced in the +/44insG rats. The +/44insG rats that had received tadalafil had a worse survival with a significant increase in RV/(LV + S), %MWT in distal PAs and RV myocardial fibrosis compared with wild-type. Conclusions: The present study demonstrates that the Bmpr2 mutation promotes dedifferentiation of PA smooth muscle cells, late PVD and RV myocardial fibrosis and adversely impacts both the natural and post-treatment courses of MCT-PH in rats with significant effects only in the late stages and warrants preclinical studies using this new genetic model to optimize treatment outcomes of heritable PAH.

DOI： 10.1186/s12931-022-02005-w

[Impact of the COVID-19 pandemic on national and prefectural health and nutrition examination surveys: A report by the Monitoring Report Committee of the Japanese Society of Public Health]. Open Access

Kubo A, Kuno K, Maruyama K, Tsukinoki R, Noda H, Egawa K, Shibuya I, Sei M, Chihara M, Nishina K, Yatsuya H

[Nihon koshu eisei zasshi] Japanese journal of public health Vol. 69 ( 8 ) page： 586 - 594 2022.8

Perinatal hypoxia aggravates occlusive pulmonary vasculopathy in SU5416/ hypoxia-treated rats later in life

Oshita H., Sawada H., Mitani Y., Tsuboya N., Kabwe J.C., Maruyama J., Yusuf A., Ito H., Okamoto R., Otsuki S., Yodoya N., Ohashi H., Oya K., Kobayashi Y., Kobayashi I., Dohi K., Nishimura Y., Saitoh S., Maruyama K., Hirayama M.

American Journal of Physiology - Lung Cellular and Molecular Physiology Vol. 323 ( 2 ) page： L178 - L192 2022.8

Publisher：American Journal of Physiology - Lung Cellular and Molecular Physiology

Pulmonary arterial hypertension (PAH) is a fatal disease, which is characterized by occlusive pulmonary vascular disease (PVD) in small pulmonary arteries. It remains unknown whether perinatal insults aggravate occlusive PVD later in life. We tested the hypothesis that perinatal hypoxia aggravates PVD and survival in rats. PVD was induced in rats with/without perinatal hypoxia (embryonic day 14 to postnatal day 3) by injecting SU5416 at 7 wk of age and subsequent exposure to hypoxia for 3 wk (SU5416/ hypoxia). Hemodynamic and morphological analyses were performed in rats with/without perinatal hypoxia at 7 wk of age (baseline rats, n = 12) and at 15 wk of age in 4 groups of rats: SU5416/hypoxia or control rats with/without perinatal hypoxia (n = 40). Pulmonary artery smooth muscle cells (PASMCs) from the baseline rats with/without perinatal hypoxia were used to assess cell proliferation, inflammation, and genomic DNA methylation profile. Although perinatal hypoxia alone did not affect survival, physiological, or pathological parameters at baseline or at the end of the experimental period in controls, perinatal hypoxia decreased weight gain and survival rate and increased right ventricular systolic pressure, right ventricular hypertrophy, and indices of PVD in SU5416/hypoxia rats. Perinatal hypoxia alone accelerated the proliferation and inflammation of cultured PASMCs from baseline rats, which was associated with DNA methylation. In conclusion, we established the first fatal animal model of PAH with worsening hemodynamics and occlusive PVD elicited by perinatal hypoxia, which was associated with hyperproliferative, proinflammatory, and epigenetic changes in cultured PASMCs. These findings provide insights into the treatment and prevention of occlusive PVD.

DOI： 10.1152/ajplung.00422.2021

Enhanced Effects of Chronic Restraint-Induced Psychological Stress on Total Body Fe-Irradiation-Induced Hematopoietic Toxicity in <i>Trp53</i>-Heterozygous Mice

Wang, B; Katsube, T; Tanaka, K; Ninomiya, Y; Hirakawa, H; Liu, CH; Maruyama, K; Varès, G; Kito, S; Nakajima, T; Fujimori, A; Nenoi, M

LIFE-BASEL Vol. 12 ( 4 ) 2022.4

Language：English Publisher：Life

Humans are exposed to both psychological stress (PS) and radiation in some scenarios such as manned deep-space missions. It is of great concern to verify possible enhanced deleterious effects from such concurrent exposure. Pioneer studies showed that chronic restraint-induced PS (CRIPS) could attenuate Trp53 functions and increase gamma-ray-induced carcinogenesis in Trp53-heterozygous mice while CRIPS did not significantly modify the effects on X-ray-induced hemato-poietic toxicity in Trp53 wild-type mice. As high-linear energy transfer (LET) radiation is the most important component of space radiation in causing biological effects, we further investigated the effects of CRIPS on high-LET iron-particle radiation (Fe)-induced hematopoietic toxicity in Trp53-heterozygous mice. The results showed that CRIPS alone could hardly induce significant alteration in hematological parameters (peripheral hemogram and micronucleated erythrocytes in bone mar-row) while concurrent exposure caused elevated genotoxicity measured as micronucleus incidence in erythrocytes. Particularly, exposure to either CRISP or Fe-particle radiation at a low dose (0.1 Gy) did not induce a marked increase in the micronucleus incidence; however, concurrent exposure caused a significantly higher increase in the micronucleus incidence. These findings indicated that CRIPS could enhance the deleterious effects of high-LET radiation, particularly at a low dose, on the hematopoietic toxicity in Trp53-heterozygous mice.

DOI： 10.3390/life12040565

Effectiveness of lacosamide in children and young adults previously treated with other sodium channel blockers

Suzuki, T; Natsume, J; Kumai, S; Maki, Y; Yamamoto, H; Numoto, S; Narahara, S; Kubota, T; Tsuji, T; Kato, T; Yamada, K; Maruyama, K; Okumura, A; Takahashi, Y; Kidokoro, H

EPILEPSY & BEHAVIOR Vol. 125 page： 108397 2021.12

Language：English Publisher：Epilepsy and Behavior

Purpose: This multicenter study examined the effectiveness and tolerability of lacosamide (LCM) for children and young adults with epilepsy, particularly in patients who had previously been treated with other sodium channel blockers (SCBs) and the difference in effectiveness and tolerability when using other concomitant SCBs. Methods: We retrospectively studied the clinical information of patients aged <30 years given LCM to treat epilepsy. The effectiveness and adverse events (AEs) of LCM and the other SCBs were investigated. Factors related to the effectiveness and AEs of LCM, such as the number of antiepileptic drugs (AEDs) tried before LCM and concomitantly used SCBs, were also studied. Results: We enrolled 112 patients (median age = 11 years). One year after starting LCM, 29% of the patients were seizure free, and 50% had a ≥50% seizure reduction. Of the patients, 17% experienced AEs, the most common being somnolence. A ≥50% seizure reduction was observed for LCM in 30% of patients in whom other SCBs had not been effective. Lacosamide produced a ≥50% seizure reduction in 35% of the patients taking one concomitant SCB. By contrast, no patients had ≥50% seizure reduction, and 33% developed AEs, when LCM was administered concomitantly with two SCBs. Conclusions: Lacosamide was effective in 30% of children and young adults in whom other SCBs had not been effective. The effectiveness of LCM may differ from that of other SCBs, and it is worth trying in patients with epilepsy resistant to other AEDs.

DOI： 10.1016/j.yebeh.2021.108397

Synergistic Effects of Chronic Restraint-Induced Stress and Low-Dose <SUP>56</SUP>Fe-particle Irradiation on Induction of Chromosomal Aberrations in <i>Trp53</i>-Heterozygous Mice

Katsube, T; Wang, B; Tanaka, K; Ninomiya, Y; Hirakawa, H; Liu, CH; Maruyama, K; Vares, G; Liu, Q; Kito, S; Nakajima, T; Fujimori, A; Nenoi, M

RADIATION RESEARCH Vol. 196 ( 1 ) page： 100 - 112 2021.7

Language：English Publisher：Radiation Research

Astronauts can develop psychological stress (PS) during space flights due to the enclosed environment, microgravity, altered light-dark cycles, and risks of equipment failure or fatal mishaps. At the same time, they are exposed to cosmic rays including high atomic number and energy (HZE) particles such as iron-56 (Fe) ions. Psychological stress or radiation exposure can cause detrimental effects in humans. An earlier published pioneering study showed that chronic restraint-induced psychological stress (CRIPS) could attenuate Trp53 functions and increase carcinogenesis induced by low-linear energy transfer (LET) γrays in Trp53-heterozygous (Trp53 +/-) mice. To elucidate possible modification effects from CRIPS on high-LET HZE particle-induced health consequences, Trp53 +/-mice were received both CRIPS and accelerated Fe ion irradiation. Six-week-old Trp53 +/-C57BL/6N male mice were restrained 6 h per day for 28 consecutive days. On day 8, they received total-body Fe-particle irradiation (Fe-TBI, 0.1 or 2 Gy). Metaphase chromosome spreads prepared from splenocytes at the end of the 28-day restraint regimen were painted with the fluorescence in situ hybridization (FISH) probes for chromosomes 1 (green), 2 (red) and 3 (yellow). Induction of psychological stress in our experimental model was confirmed by increase in urinary corticosterone level on day 7 of restraint regimen. Regardless of Fe-TBI, CRIPS reduced splenocyte number per spleen at the end of the 28-day restraint regimen. At 2 Gy, Fe-TBI alone induced many aberrant chromosomes and no modifying effect was detected from CRIPS on induction of aberrant chromosomes. Notably, neither Fe-TBI at 0.1 Gy nor CRIPS alone induced any increase in the frequency of aberrant chromosomes, while simultaneous exposure resulted in a significant increase in the frequency of chromosomal exchanges. These findings clearly showed that CRIPS could enhance the frequency of chromosomal exchanges induced by Fe-TBI at a low dose of 0.1 Gy.

DOI： 10.1667/RADE-20-00218.1

Risks of ACTH therapy for West syndrome following BCG vaccination

Maki, Y; Natsume, J; Hori, I; Takeuchi, T; Negishi, Y; Kubota, T; Maruyama, K; Nakata, T; Yamamoto, H; Tanaka, M; Kawaguchi, M; Suzuki, T; Shiraki, A; Sawamura, F; Kidokoro, H

EPILEPSY & BEHAVIOR Vol. 118 page： 107924 2021.5

Language：English Publisher：Epilepsy and Behavior

Objective: Bacille de Calmette et Guérin (BCG) is a live vaccine for tuberculosis that is administered to all infants in Japan. Adrenocorticotropic hormone (ACTH) therapy for West syndrome (WS) causes immunosuppression and may result in BCG infection after BCG vaccination. We evaluated the safety of ACTH therapy initiated shortly after BCG vaccination. Methods: We analyzed patients with WS who received ACTH therapy between 2005 and 2018. We evaluated the interval between BCG and ACTH therapy, and the rate of BCG infection during and after ACTH therapy, by retrospective chart review. Results: Seventy-nine patients were included in the analysis. Twenty-three patients received ACTH therapy prior to BCG vaccination. For the remaining 56 patients, the median interval between BCG vaccination and the start of ACTH therapy (BCG–ACTH interval) was 91.5 (range 14–280) days. The BCG–ACTH interval was shorter in patients with unknown than in those with known etiologies. It was <8 weeks in 13 patients (10 with unknown and 3 with known etiologies). The minimum BCG–ACTH interval was 14 days. Six patients with epileptic spasms received BCG vaccinations because physicians did not recognize their seizures. None of the patients developed BCG infection. Conclusion: No patients who received ACTH therapy after BCG, even at an interval of 8 weeks, developed BCG infection. The timing of ACTH therapy initiation should be based on the risk of BCG-related adverse events and the adverse effects of any delay.

DOI： 10.1016/j.yebeh.2021.107924

MRI findings in children with congenital cytomegalovirus infection retrospectively diagnosed with dried umbilical cord

Kidokoro, H; Shiraki, A; Torii, Y; Tanaka, M; Yamamoto, H; Kurahashi, H; Maruyama, K; Okumura, A; Natsume, J; Ito, Y

NEURORADIOLOGY Vol. 63 ( 5 ) page： 761 - 768 2021.5

Language：English Publisher：Neuroradiology

Purpose: Brain MRI provides important information about suspected congenital CMV infection in neonatally underdiagnosed children. This study aimed to describe MRI findings in children in whom congenital CMV infection was not suspected during the neonatal period and was proven retrospectively. Methods: We enrolled 31 children referred to the pediatric neurology clinic with neurological symptoms who were proven to have congenital CMV infection based on dried umbilical cord samples. Upon diagnosis, MR and CT images were assessed using the van der Knaap scoring system integrated with additional variables. Two investigators independently assessed all images. Results: The age at diagnosis was < 12 months in 14, 12–24 months in 11, and > 24 months in 6 patients. The initial symptom triggering clinic referral was delayed development in 22, seizure in 5, deafness in 3, and hemiplegia in 1 patient. Of the 31 children, 30 had a white matter (WM) abnormality predominant in the deep WM of the parietal lobe (n = 25). Anterior temporal lesions were observed in 21 children. Cortical lesions were observed in 7 children, suggestive of polymicrogyria. No child had cerebellar or brainstem abnormalities. Brain CT was performed in 22 of 31 children, and 11 showed punctate cerebral calcification in the periventricular and/or deep WM. Conclusion: Patients with congenital CMV infection with delayed neurological symptoms show a relatively uniform pattern of parietal-dominant multifocal WM lesions and anterior temporal lesions, with or without polymicrogyria.

DOI： 10.1007/s00234-020-02603-9

Semaphorin3E-PlexinD1 signaling in coronary artery and lymphatic vessel development with clinical implications in myocardial recovery

Maruyama K., Naemura K., Arima Y., Uchijima Y., Nagao H., Yoshihara K., Singh M.K., Uemura A., Matsuzaki F., Yoshida Y., Kurihara Y., Miyagawa-Tomita S., Kurihara H.

iScience Vol. 24 ( 4 ) 2021.4

Publisher：iScience

Blood and lymphatic vessels surrounding the heart develop through orchestrated processes from cells of different origins. In particular, cells around the outflow tract which constitute a primordial transient vasculature, referred to as aortic subepicardial vessels, are crucial for the establishment of coronary artery stems and cardiac lymphatic vessels. Here, we revealed that the epicardium and pericardium-derived Semaphorin 3E (Sema3E) and its receptor, PlexinD1, play a role in the development of the coronary stem, as well as cardiac lymphatic vessels. In vitro analyses demonstrated that Sema3E may demarcate areas to repel PlexinD1-expressing lymphatic endothelial cells, resulting in proper coronary and lymphatic vessel formation. Furthermore, inactivation of Sema3E-PlexinD1 signaling improved the recovery of cardiac function by increasing reactive lymphangiogenesis in an adult mouse model of myocardial infarction. These findings may lead to therapeutic strategies that target Sema3E-PlexinD1 signaling in coronary artery diseases.

DOI： 10.1016/j.isci.2021.102305

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