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Cardiofaciocutaneous syndrome (CFC) is a rare genetic disorder that presents with cardiac, craniofacial, and cutaneous symptoms, and is often accompanied by neurological abnormalities, including neurodevelopmental disorders and epilepsy. Regarding epilepsy in CFC, the onset of seizures commonly occurs in childhood. Since research data has mainly been collected from young patients with relatively short observation period, there is insufficient information regarding adult-onset epilepsy in CFC. Here, we report the long-term clinical course of epilepsy and other complications in a 45-year-old female with genetically confirmed CFC carrying a pathogenic de novo heterozygous variant of MAP2K1, c.389 A>G (p.Tyr130Cys). The patient presented psychomotor delay from infancy and had severe intellectual disability with autistic features. At the age of 30, she first developed combined generalized and focal epilepsy that was resistant to anti-seizure medication. Her refractory epilepsy was fairly controlled with a combination of three anti-seizure medications, especially lacosamide, which effectively suppressed both generalized and focal seizures. The present case provides detailed information regarding the clinical course and treatment of adult-onset epilepsy, which may be useful for optimal treatment and prognostic prediction of CFC.

For autonomous mobile robots to work safely in human-coexistent environments, human-velocity estimation is essential. However, the human body periodically fluctuates to the front, rear, right, and left while walking. Also, a significant estimation error occurs due to the vibration of sensors installed in the robot. Quick trajectory adjustment requires high-accuracy and low-latency estimation, but these are in a trade-off relationship. We thus propose a human velocity estimation system (VES) using the Kalman filter (KF) and least squares (LS) with adjustable window size (AWS) to control the accuracy and latency. The VES adjusts two window sizes to calculate a system noise distribution for KF and a velocity vector for LS using a newly proposed cost function, including accuracy (direction and magnitude) and latency (time delay) costs. To select window sizes suitable for walking trajectories and individual gaits, we collected human walking data, calculated the three costs, and selected the window sizes with the minimum cost. The results of experiments using a laser range finder installed on a mobile robot indicate that the cost function could reveal window sizes to increase accuracy or reduce latency depending on walking trajectories and individual gaits, and the VES with AWS could enhance the performance of estimating human walking velocity for mobile robots.

Abstract Aim Mutation spectrum of TP53 in gastric cancer (GC) has been investigated world-widely, but a comparison of mutation spectrum among GCs from various regions in the world are still sparsely documented. In order to identify the difference of TP53 mutation spectrum in GCs in Eastern Europe and in East Asia, we sequenced TP53 in GCs from Eastern Europe, Lujiang (China), and Yokohama, Kanagawa (Japan) and identified the feature of TP53 mutations of GC in these regions. Subjects and method In total, 689 tissue samples of GC were analyzed: 288 samples from East European populations (25 from Hungary, 71 from Poland and 192 from Romania), 268 from Yokohama, Kanagawa, Japan and 133 from Lujiang, Anhui province, China. DNA was extracted from FFPE tissue of Chinese, East European cases; and from frozen tissue of Japanese GCs. PCR products were direct-sequenced by Sanger method, and in ambiguous cases, PCR product was cloned and up to 8 clones were sequenced. We used No. NC_000017.11(hg38) as the reference sequence of TP53. Mutation patterns were categorized into nine groups: six base substitutions, insertion, deletion and deletion-insertion. Within G:C > A:T mutations the mutations in CpG and non-CpG sites were divided. The Cancer Genome Atlas data (TCGA, ver.R20, July, 2019) having somatic mutation list of GCs from Whites, Asians, and other ethnicities were used as a reference for our data. Results The most frequent base substitutions were G:C > A:T transition in all the areas investigated. The G:C > A:T transition in non-CpG sites were prominent in East European GCs, compared with Asian ones. Mutation pattern from TCGA data revealed the same trend between GCs from White (TCGA category) vs Asian countries. Chinese and Japanese GCs showed higher ratio of G:C > A:T transition in CpG sites and A:T > G:C mutation was more prevalent in Asian countries. Conclusion The divergence in mutation spectrum of GC in different areas in the world may reflect various pathogeneses and etiologies of GC, region to region. Diversified mutation spectrum in GC in Eastern Europe may suggest GC in Europe has different carcinogenic pathway of those from Asia.

Abstract Background The cerebellum plays an important role in motor control, however, its involvement in epilepsy has not been fully understood. Arterial spin labelling perfusion magnetic resonance image (ASL) is a noninvasive method to evaluate cerebral and cerebellar blood flow. We investigated cerebellar perfusion in patients with epileptic seizures using ASL. Methods Adult patients with epileptic seizures who underwent ASL in three post labeling delay (PLD) conditions (1525, 1800, and 2500 msec) and conventional electroencephalography (EEG) on the same day were investigated. Clinical and EEG characteristics of them were retrospectively analyzed. Results Six patients (6 women, age; 36.2 ± 17.9 years (mean ± SD)) showed hyperperfusion in selective areas in the cerebellar paravermis of lobule VIIb. One patient with generalized epilepsy (tentative diagnosis of juvenile myoclonic epilepsy or epilepsy with myoclonic absences) showed unilateral hypoperfusion in PLD 1525 msec and hyperperfusion in PLD 1800 and 2500 msec at the area while EEG showed generalized spike-wave complexes. After successful treatment, these perfusion abnormalities disappeared. In two patients with focal epilepsy manifesting with asymmetrical motor symptoms, cerebellar hyperperfusion was found on the opposite side to the seizure focus estimated by seizure semiology. Besides hyperperfusion of the VIIb lobule, hypoperfusion at the same area was detected in shorter PLD condition in four patients and in longer PLD condition in one patient. Conclusion The cerebellar paravermis of lobule VIIb can be a component of motor circuit and participate in epileptic network in humans. Cerebellar perfusion abnormalities can be associated with neurovascular coupling via capillary bed.

Abstract Biomarkers for selecting gastric cancer (GC) patients likely to benefit from sequential paclitaxel treatment followed by fluorinated-pyrimidine-based adjuvant chemotherapy (sequential paclitaxel) were investigated using tissue samples of patients recruited into SAMIT, a phase III randomized controlled trial. Total RNA was extracted from 556 GC resection samples. The expression of 105 genes was quantified using real-time PCR. Genes predicting the benefit of sequential paclitaxel on overall survival, disease-free survival, and cumulative incidence of relapse were identified based on the ranking of p-values associated with the interaction between the biomarker and sequential paclitaxel or monotherapy groups. Low VSNL1 and CD44 expression predicted the benefit of sequential paclitaxel treatment for all three endpoints. Patients with combined low expression of both genes benefitted most from sequential paclitaxel therapy (hazard ratio = 0.48 [95% confidence interval, 0.30–0.78]; p

Simple Summary: There is no clear preference between S-1 and capecitabine in combination with platinum agent as first-line therapy for patients with HER2-negative unresectable advanced or recurrent gastric cancer (GC) with measurable disease. Although a distinguishing use of S-1 versus capecitabine based on histological classification has been studied, the present integrated analysis, using 162 individual participant data of GC patients with measurable disease, is the first to show that S-1 plus cisplatin (SP) achieves deeper tumor shrinkage than capecitabine plus cisplatin (XP), leading a longer overall survival although no differences in response rate or progression-free survival in differentiated GC. On the other hand, in undifferentiated GC, SP consistently showed better clinical results than XP. These findings thus have implications for the choice of oral fluoropyrimidine in the era of first line therapy in combination with oxaliplatin and immune checkpoint inhibitor. It has been suggested that the therapeutic efficacy of S-1 + cisplatin (SP) and capecitabine + cisplatin (XP) may differ depending on the histology of the tumor, but no clear evidence exists. Individual participant data were obtained from three randomized phase II trials in which such patients received either SP (S-1 [40–60 mg twice daily for 21 days] plus cisplatin [60 mg/m2 on day 8], every 5 weeks) or XP (capecitabine [1000 mg/m2 twice daily for 14 days] plus cisplatin [80 mg/m2 on day 1], every 3 weeks). A total of 162 patients were included, with 79 patients in the SP arm and 83 patients in the XP arm. Although there was also no difference between arms in ORR according to histological classification, differentiated tumors showed a significantly better OS (but not PFS) for SP versus XP that was associated with a deeper tumor shrinkage. Undifferentiated tumors showed a consistently better OS, and PFS for SP versus XP, likely because cases without tumor shrinkage tended to be fewer for SP. Our data thus showed that SP was superior to XP in this setting, but there were qualitative differences in therapeutic efficacy dependent on tumor histology. [ABSTRACT FROM AUTHOR]

Background/aim: The randomized phase II COMPASS trial revealed that neither the regimen nor the number of courses of preoperative neoadjuvant chemotherapy (NAC) for locally advanced gastric cancer (GC) significantly influence overall survival (OS). However, the impact of NAC regimens on OS may vary from patient to patient. The aim of this study was to identify biomarkers that can predict more appropriate individualized NAC regimens for improved prognosis using biopsy specimens from the COMPASS trial., Patients and Methods: RNA was extracted from endoscopic biopsy specimens of primary tumors obtained prior to NAC and real-time PCR analysis of 127 genes was conducted to identify those significantly affecting survival in the context of specific NAC regimens., Results: THBS1, MSI1, and IGF2BP3 were identified as significant factors for stratifying survival among different NAC regimens, with statistically significantly interaction p values. Immunohistochemical analysis confirmed that the protein levels of THBS1, MSI1, and IGF2BP3 strongly correlated with their gene expression levels, validating these proteins as reliable biomarkers., Conclusion: This study effectively identified THBS1, MSI1, and IGF2BP3 as promising biomarkers for personalizing NAC regimens in patients with locally advanced GC. By tailoring NAC based on these biomarkers, it is possible to enhance survival outcomes and advance personalized treatment strategies. The findings underscore the potential for incorporating biomarker-guided approaches into clinical trials, aiming to refine and optimize NAC regimens for improved patient-specific treatment efficacy., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)