1.White Matter Hyperintensities and Neuropsychiatric Symptoms in Neurodegenerative Diseases
Shigeki KATAKAMI ; Hideki KANEMOTO ; Daiki TAOMOTO ; Yuto SATAKE ; Takashi SUEHIRO ; Shunsuke SATO ; Kenji YOSHIYAMA ; Tetsuo KASHIBAYASHI ; Ryuichi TAKAHASHI ; Kenji TAGAI ; Shunichiro SHINAGAWA ; Kazunari ISHII ; Hiroaki KAZUI ; Manabu IKEDA
Journal of Clinical Neurology 2026;22(2):183-192
Background:
and Purpose Neuropsychiatric symptoms (NPS) are frequent in dementia and mild cognitive impairment (MCI), yet their reported associations with white matter hyperintensities (WMHs) remain inconsistent. We examined item-level associations between WMHs and NPS across Alzheimer’s disease dementia (ADD), dementia with Lewy bodies (DLB), and amnestic MCI (aMCI).
Methods:
This multicenter retrospective study involved 523 patients: 276 with ADD, 67 with DLB, and 180 with aMCI. Three-dimensional T1-weighted and T2–fluid-attenuated inversion recovery magnetic resonance images were processed with BAAD (Brain Anatomical Analysis using Diffeomorphic Deformation) software to quantify WMH volume (WMHV) and gray matter volume (GMV), normalized to total intracranial volume (TIV). NPS were assessed using the Neuropsychiatric Inventory. Multiple regression analyses were performed within each group, adjusting for GMV/TIV, age, sex, years of education, Clinical Dementia Rating–Sum of Boxes score, and institution.
Results:
In the aMCI group, higher WMHV/TIV was positively associated with depression, apathy, and disinhibition, and negatively with delusions. Subregional analyses revealed NPSspecific topographic patterns. No significant associations were detected in the ADD or DLB group. GMV/TIV was positively associated with delusions in the ADD group, but negatively associated with hallucinations in the DLB group.
Conclusions
Associations between WMHs and NPS were evident in the aMCI group but absent in the ADD and DLB groups, suggesting a stage-dependent effect. WMHs may contribute to NPS primarily in prodromal stages, whereas their influence may be overshadowed by neurodegenerative pathology in dementia. Clarifying the mechanisms underlying WMHs is critical for evaluating their potential as intervention targets.
2.Establishment of a Multilocus Sequence Typing Scheme for Pasteurella canis Using Isolates from Infected Humans and Diseased Companion Animals
Haruno YOSHIDA ; Jae-Seok KIM ; Takahiro MAEDA ; Mieko GOTO ; Yuzo TSUYUKI ; Kenichi SHIZUNO ; Takashi TAKAHASHI
Annals of Laboratory Medicine 2025;45(3):300-311
Background:
Multilocus sequence typing (MLST) is well-established for Pasteurella multocida but remains undeveloped for Pasteurella canis. We established MLST for P. canis using isolates from humans and companion animals in Japan and Korea to gain insights into its population biology.
Methods:
We analyzed 39 and 22 isolates from companion animals and humans, respectively. We selected seven housekeeping genes—adk, aroA, deoD, gdhA, g6pd, mdh, and pgi—used in P. multocida MLST. Primer pairs for PCR amplification and sequencing were designed based on conserved sites in 10 whole-genome sequences. We determined frag-ment sequences, variable sites, allelic profiles, and sequence types (STs) of each isolate. A phylogenetic tree of concatenated sequences was constructed using the goeBURST algo-rithm to identify STs and clonal complexes (CCs). ompAM, encoding outer membrane protein A, was genotyped for molecular characterization.
Results:
The sequenced fragment lengths and allele numbers of the seven genes wereHallym University College of Medicine, 424, 451, 483, 439, 429, 419, and 440 bp and 16, 13, 15, 18, 22, 19, and 18, respec-tively. ST1–ST47, including CC2, CC10, CC18, CC31, and CC33, were diversely distributed among the isolates from different hosts/countries. In the seven-gene phylogenetic tree, apart from P. multocida, all isolates clustered together. goeBURST diagrams revealed di-verse ST distributions among different hosts (animal/human) and countries (Japan/Ko-rea/others). We found clusters 1–4 in ompA genotyping, indicating that MLST discrimination is higher than ompA typing discrimination.
Conclusions
We established MLST for P. canis isolates from humans and companion ani-This is an Open Access article distributed under mals in Japan and Korea, thereby providing a robust tool for population biology studies.
4.Whole-genome sequencing applications for evolution of clinical microbiology
Annals of Clinical Microbiology 2025;28(4):22-
In the present review, we systematically examine the diverse applications of whole-genome sequencing (WGS) and next-generation sequencing (NGS) to elucidate the evolution of clinical microbiology. The review aims to provide novel insight and to improve understanding of the applications of WGS in clinical microbiology laboratories. It is organized into the following sections: (1) the various types of NGS machines; (2) NGS workflows for obtaining genome sequences; (3) comparative genomic analysis; (4) RNA-seq (transcriptome) analysis; (5) genome-based bacterial typing; (6) genome-based antimicrobial resistance (AMR) detection;and (7) identification of integrative and conjugative elements carrying AMR gene(s). Four figures and three tables are provided to illustrate this information. The discussion focuses on WGS applications using several genera of microorganisms (Streptococcus, Enterococcus, Staphylococcus, Pasteurella, and Mycobacterium). Overall, WGS and related NGS technologies provide innovative clinical microbiology laboratory studies based on high-throughput genomic results for pathogen identification, tracking, and AMR/virulence profiling. In line with the concept of “One Health,” human and animal microbiology laboratories should pay careful attention to the drastically dynamic evolution of WGS and related NGS technologies.
5.Proposal of a new indicator of hip compensation for spinopelvic–hip mismatch: a retrospective study in Japan
Ryo FUJITA ; Kohei TAKAHASHI ; Ko HASHIMOTO ; Kazuyoshi BABA ; Kenichiro YAHATA ; Takahiro ONOKI ; Takashi AKI ; Keisuke ISHIKAWA ; Toshimi AIZAWA
Asian Spine Journal 2025;19(6):967-977
Methods:
A total of 209 patients with osteoporosis and 54 with adult spinal deformities were included. Patients were divided into two groups based on pelvic incidence–lumbar lordosis (PI–LL): <20° and ≥20° groups. The sagittal vertical axis (SVA), thoracic kyphosis, PI, pelvic tilt (PT), LL, sacral slope, and pelvic femoral angle (PFA) were measured. Health-related quality of life (HRQOL) was assessed in 86 patients using the Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ). A new index, PFA–(PI–LL), was defined as spinopelvic–hip mismatch. Correlation coefficients were calculated for each radiographic parameter, and the coefficient of determination (R2) for the relationship of each parameter with SVA was evaluated in both groups. The correlations between SVA, PT, PI–LL, PFA–(PI–LL), and JOABPEQ domain scores were also analyzed.
Results:
PI–LL correlated with PFA in the PI–LL <20° group (r=0.56, p<0.001) but not in the PI–LL ≥20° group. Among all parameters, PFA–(PI–LL) demonstrated the strongest association with SVA, indicating its superior ability to explain variations in sagittal alignment in both groups and across all patients (all patients, R2=0.77). Significant correlations were observed between the radiographic parameters and JOABPEQ scores across all domains.
Conclusions
PFA–(PI–LL), which represented spinopelvic–hip mismatch, was a reliable indicator of hip compensatory function in terms of anterior trunk inclination and HRQOL.
6.Lenvatinib and pembrolizumab versus platinum doublet chemotherapy as second-line therapy for advanced or recurrent endometrial cancer
Yutaka YONEOKA ; Tsukuru AMANO ; Akimasa TAKAHASHI ; Hiroki NISHIMURA ; Mari DEGUCHI ; Hiroyuki YAMANAKA ; Yuji TANAKA ; Shunichiro TSUJI ; Takashi MURAKAMI
Obstetrics & Gynecology Science 2024;67(6):534-540
Objective:
There is no consensus on whether platinum doublet chemotherapy or lenvatinib and pembrolizumab (LEN/PEM) is superior for advanced or recurrent endometrial cancer. Thus, this study aimed to compare the prognosis and adverse events in patients with advanced or recurrent endometrial cancer treated with platinum doublet chemotherapy or LEN/PEM.
Methods:
We retrospectively reviewed the medical records of patients who received platinum doublet chemotherapy or LEN/PEM at our institution for advanced or recurrent endometrial cancer and had a history of platinum-based chemotherapy between January 2013 and August 2023.
Results:
During the study period, 11 regimens were identified in the platinum doublet chemotherapy group, and 11 regimens were identified in the LEN/PEM group. The objective response rates of the platinum doublet chemotherapy and LEN/ PEM groups were 36.4% and 54.5% (P=0.67), respectively. The 6-month progression-free survival (PFS) rates of the platinum doublet chemotherapy and LEN/PEM groups were 27.3% (95% confidence interval [CI], 13.8%-40.7%) and 70.0% (95% CI, 55.5%-84.5%), respectively. The differences were significant between the two groups. Multivariate analyses of histology, prior lines of chemotherapy, platinum-free intervals, and regimens revealed that the LEN/PEM group had significantly better PFS rates.
Conclusion
Treatment with LEN/PEM resulted in significantly longer PFS than that of treatment with platinum doublet chemotherapy in patients with advanced and recurrent endometrial cancer. However, further large-scale studies are required to validate these findings.
7.Lenvatinib and pembrolizumab versus platinum doublet chemotherapy as second-line therapy for advanced or recurrent endometrial cancer
Yutaka YONEOKA ; Tsukuru AMANO ; Akimasa TAKAHASHI ; Hiroki NISHIMURA ; Mari DEGUCHI ; Hiroyuki YAMANAKA ; Yuji TANAKA ; Shunichiro TSUJI ; Takashi MURAKAMI
Obstetrics & Gynecology Science 2024;67(6):534-540
Objective:
There is no consensus on whether platinum doublet chemotherapy or lenvatinib and pembrolizumab (LEN/PEM) is superior for advanced or recurrent endometrial cancer. Thus, this study aimed to compare the prognosis and adverse events in patients with advanced or recurrent endometrial cancer treated with platinum doublet chemotherapy or LEN/PEM.
Methods:
We retrospectively reviewed the medical records of patients who received platinum doublet chemotherapy or LEN/PEM at our institution for advanced or recurrent endometrial cancer and had a history of platinum-based chemotherapy between January 2013 and August 2023.
Results:
During the study period, 11 regimens were identified in the platinum doublet chemotherapy group, and 11 regimens were identified in the LEN/PEM group. The objective response rates of the platinum doublet chemotherapy and LEN/ PEM groups were 36.4% and 54.5% (P=0.67), respectively. The 6-month progression-free survival (PFS) rates of the platinum doublet chemotherapy and LEN/PEM groups were 27.3% (95% confidence interval [CI], 13.8%-40.7%) and 70.0% (95% CI, 55.5%-84.5%), respectively. The differences were significant between the two groups. Multivariate analyses of histology, prior lines of chemotherapy, platinum-free intervals, and regimens revealed that the LEN/PEM group had significantly better PFS rates.
Conclusion
Treatment with LEN/PEM resulted in significantly longer PFS than that of treatment with platinum doublet chemotherapy in patients with advanced and recurrent endometrial cancer. However, further large-scale studies are required to validate these findings.
8.Comparative Genomic Analysis of Staphylococcal Cassette Chromosome mec Type V Staphylococcus aureus Strains and Estimation of the Emergence of SCCmec V Clinical Isolates in Korea
Takashi TAKAHASHI ; Hyaekang KIM ; Han-Sung KIM ; Hyun Soo KIM ; Wonkeun SONG ; Jae-Seok KIM
Annals of Laboratory Medicine 2024;44(1):47-55
Background:
Staphylococcal cassette chromosome mec type V (SCCmec V) methicillin-resistant Staphylococcus aureus (MRSA) has been recovered from patients and livestock.Using comparative genomic analyses, we evaluated the phylogenetic emergence of SCCmec V after transmission from overseas donor strains to Korean recipient strains.
Methods:
Sixty-three complete MRSA SCCmec V genomes (including six Korean clinical isolates) were used to construct a phylogenetic tree. Single-nucleotide polymorphisms were identified using Snippy, and a maximum-likelihood-based phylogenetic tree was constructed using RAxML. The possible emergence of the most common ancestor was estimated using BactDating. To estimate mecA horizontal gene transfer (HGT) events, Rangerdtl was applied to 818 SCCmec V strains using publicly available whole-genome data.
Results:
The phylogenetic tree showed five major clades. German strains formed a major clade; their possible origin was traced to the 1980s. The emergence of Korean SCCmec V clinical isolates was traced to 2000–2010. mecA HGT events in Staphylococcus spp. were identified in seven strains. P7 (Hong Kong outbreak strain) served as the donor strain for two Korean sequence type (ST) 59 strains, whereas the other five recipient strains emerged from different SCCmec V donors.
Conclusions
Most Korean SCCmec V strains may have emerged during 2000–2010. A unique MRSA SCCmec V strain, ST72 (a Korean common type of community-associated MRSA), was also identified. The genomic dynamics of this clone with a zoonotic background should be monitored to accurately understand MRSA evolution.
9.Outcome of intradiscal condoliase injection therapy for patients with recurrent lumbar disc herniation
Noritaka SUZUKI ; Yawara EGUCHI ; Takashi HIRAI ; Takuya TAKAHASHI ; Yohei TAKAHASHI ; Kota WATANABE ; Tomohiro BANNO ; Kyohei SAKAKI ; Satoshi MAKI ; Yuuichi TAKANO ; Yuki TANIGUCHI ; Yasuchika AOKI ; Takamitsu KONISHI ; Yutaka HIRAIZUMI ; Masatsune YAMAGATA ; Akihiro HIRAKAWA ; Seiji OHTORI
Asian Spine Journal 2024;18(4):550-559
Methods:
The study participants were 249 patients who underwent intradiscal condoliase injection for LDH at nine participating institutions, including 241 patients with initial LDH (group C) and eight with recurrent LDH (group R). Patient characteristics including age, sex, body mass index, disease duration, intervertebral LDH level, smoking history, and diabetes history were evaluated. Low back pain/leg pain Numerical Rating Scale (NRS) scores and the Oswestry Disability Index (ODI) were used to evaluate clinical symptoms before treatment and at 6 months and 1 year after treatment.
Results:
Low back pain NRS scores (before treatment and at 6 months and 1 year after treatment, respectively) in group C (4.9 → 2.6 → 1.8) showed significant improvement until 1 year after treatment. Although a tendency for improvement was observed in group R (3.5 → 2.8 → 2.2), no significant difference was noted. Groups C (6.6 → 2.4 → 1.4) and R (7.0 → 3.1 → 3.2) showed significant improvement in the leg pain NRS scores after treatment. Group C (41.4 → 19.5 → 13.7) demonstrated significant improvement in the ODI up to 1 year after treatment; however, no significant difference was found in group R (35.7 → 31.7 → 26.4).
Conclusions
Although intradiscal condoliase injection is less effective for LDH recurrence than for initial cases, it is useful for improving leg pain and can be considered a minimally invasive and safe treatment method.
10.E-learning system to improve the endoscopic diagnosis of early gastric cancer
Kenshi YAO ; Takashi YAO ; Noriya UEDO ; Hisashi DOYAMA ; Hideki ISHIKAWA ; Satoshi NIMURA ; Yuichi TAKAHASHI
Clinical Endoscopy 2024;57(3):283-292
We developed three e-learning systems for endoscopists to acquire the necessary skills to improve the diagnosis of early gastric cancer (EGC) and demonstrated their usefulness using randomized controlled trials. The subjects of the three e-learning systems were “detection”, “characterization”, and “preoperative assessment”. The contents of each e-learning system included “technique”, “knowledge”, and “obtaining experience”. All e-learning systems proved useful for endoscopists to learn how to diagnose EGC. Lecture videos describing “the technique” and “the knowledge” can be beneficial. In addition, repeating 100 self-study cases allows learners to gain “experience” and improve their diagnostic skills further. Web-based e-learning systems have more advantages than other teaching methods because the number of participants is unlimited. Histopathological diagnosis is the gold standard for the diagnosis of gastric cancer. Therefore, we developed a comprehensive diagnostic algorithm to standardize the histopathological diagnosis of gastric cancer. Once we have successfully shown that this algorithm is helpful for the accurate histopathological diagnosis of cancer, we will complete a series of e-learning systems designed to assess EGC accurately.

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