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Occlusion of Dorsalis Pedis Artery in an Athlete
Get PDFA 17-year-old Japanese boy was admitted to our hospital with intermittent claudication. He belonged to a weightlifting team at a high school. He had occasionally dropped lightweight lifting weights on his right foot. Arteriography of the right anterior and posterior tibial arteries revealed a 4-cm total occlusion in the right dorsalis pedis artery (DPA). Intravascular ultrasonography revealed intimal thickening and thrombus formation He was diagnosed with thrombus occlusion of the right DPA due to intimal artery damage caused by lightweight weightlifting. DPA thrombosis may occur in young athletes who do not have atherosclerosis or vasculitis.Internal Medicine, 64(14), pp.2189-2191; 2025journal articl
Genomic analysis and molecular profiling of dengue viruses in Sabah, Malaysia during 2019-2020
Get PDFObjectives: Limited information is available on the distribution of dengue virus (DENV) serotypes and genotypes in Borneo, particularly, in Sabah, because most studies have focused on Peninsular Malaysia. This study aimed to investigate the serologic and molecular epidemiologic characteristics of DENV in patients from Sabah. Methods: Serum samples were collected from febrile patients in Kota Kinabalu and Lahad Datu between 2019 and 2020 at the Kota Kinabalu Public Health Laboratory. We performed virus isolation, serological testing, viremia quantification, and complete genome sequencing. Results: Of 188 serum samples, 89 tested positive for DENV by quantitative reverse transcription-polymerase chain reaction: 20 DENV-1, 46 DENV-2, 20 DENV-3, and 1 DENV-4. A total of 38 viruses were successfully isolated. The isolates belonged to DENV-1 (genotypes I and IV), DENV-2 (cosmopolitan genotype) and DENV-3 (genotypes I and III). The phylogenetic analysis revealed close relationships with strains from Malaysia, Indonesia, and the Philippines. DENV-2 was the predominant serotype, whereas the highest viremia levels were observed in patients infected with DENV-3. Conclusions: To the best of our knowledge, this study provides the first detailed phylogenetic and complete genome analysis of DENV in Sabah. Continued molecular surveillance is essential to enhance our understanding of dengue transmission and support effective control strategies.IJID Regions, 16, art. no. 100712; 2025journal articl
Mediterranean fever gene variants may prevent the development of lupus nephritis in Japanese patients with systemic lupus erythematosus
Get PDFBackground: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by loss of immune tolerance, leading to systemic inflammation and organ damage. The Mediterranean fever (MEFV) gene, primarily linked to familial Mediterranean fever (FMF), has been suggested to have a protective role against SLE. However, comprehensive whole-exon analyses of MEFV and research on MEFV or FMF in non-Mediterranean populations, where MEFV exon 10 mutations are relatively rare, are limited. Methods: We conducted a whole-exon analysis of the MEFV gene in 55 Japanese patients with SLE. Patients were classified based on the presence or absence of MEFV variants, and their clinical characteristics were compared. In addition, we generated MRL/lpr mice with the human MEFV E148Q variant using CRISPR technology to examine its impact on disease phenotypes. Disease activity and kidney pathology were assessed using the established clinical and histological scoring systems. Results: Among the 55 patients, those carrying MEFV variants exhibited a significantly lower prevalence of lupus nephritis than non-carriers (P = 0.007). The number of MEFV variants was inversely associated with the risk of lupus nephritis (P = 0.03). In MRL/lpr mice, the E148Q variant was associated with reduced anti-dsDNA antibody production, reduced formation of memory B cells, and milder kidney pathology, indicating a shift from adaptive immunity to innate immune responses. Conclusions: Our findings suggest that MEFV variants, particularly the E148Q variant, may play a protective role against lupus nephritis in Japanese patients with SLE by modulating immune responses. These results provide valuable insights into the genetic factors influencing SLE severity.Frontiers in Immunology, 16, art. no. 1571208; 2025journal articl
Development of blood-brain barrier-penetrating antibodies for neutralizing tick-borne encephalitis virus in the brain
Get PDFTick-borne encephalitis virus (TBEV) belongs to the genus Flavivirus and causes tick-borne encephalitis (TBE), a disease characterized by severe neurological symptoms with a high mortality rate. Currently, no specific antiviral treatments have been developed for TBE. The blood-brain barrier (BBB) restricts drug delivery to the central nervous system, posing a major challenge in developing effective therapies targeting TBEV in the brain. In this study, we developed recombinant anti-TBEV antibodies fused with BBB-penetrating rabies virus glycoprotein (RVG) peptides to facilitate their transport across the BBB. The fusion of RVG peptides to the C-terminus of the heavy chain of whole antibodies or single-chain variable fragment had minimal impact on their neutralizing ability against TBEV. The RVG fusion enhanced antibody binding to the surface of a human brain endothelial cell line and increased permeability in an in vitro BBB model. The RVG-fused antibodies exhibited a higher transport efficiency to the brain than the non-fused antibodies following peripheral injection in mice. Notably, the peripheral administration of the RVG-fused whole antibody after viral invasion into the brain significantly neutralized TBEV in the brains of infected mice. These findings suggest that RVG-fused antibodies represent a promising therapeutic strategy for treating TBE once the virus has entered the brain.mSphere, 10(7). art. no. e00184-25; 2025journal articl
Prognostic Indicators of Preoperative Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel Efficacy in Locally Advanced Gastroesophageal and Gastric Cancer: Integrating Biomarker Analysis and Clinicopathological Factors
Get PDFPurpose: Perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) is a standard treatment for locally advanced gastric/gastroesophageal junction cancer (GC/GEJC). The impact of biomarker status on the efficacy of perioperative FLOT remains unclear. This study evaluated the association between clinicopathological features, including biomarker status, and the efficacy of perioperative FLOT in patients with resectable GC/GEJC. Patients and Methods: A retrospective observational study was conducted by reviewing medical records of patients treated with perioperative FLOT between February 2020 and March 2024. Eligible patients had histologically confirmed adenocarcinoma, resectable disease at stages cT2-4a and/or N0-3, M0, and underwent biomarker testing. Results: Among 116 eligible patients, human epidermal growth factor receptor 2 (HER2) positivity was observed in 7.8%, whereas PD-L1 combined positive score (CPS) of ≥1, ≥5, and ≥10 was detected in 90.5%, 44.0%, and 15.5% of patients, respectively. Claudin-18 isoform 2 (CLDN18.2) positivity (2+/3+ in ≥75% of tumor cells) was observed in 30.2% of patients. Major pathological response (MPR) and pathological complete response (pCR) rates were 22.4% (95% CI, 15.3 to 31.0) and 8.6% (95% CI, 4.2 to 15.3), respectively. Diffuse-type histology was a negative indicator for pathological response. CLDN18.2 expression decreased significantly after preoperative FLOT, with the median H-score declining from 285.0 to 187.5 (P < .001) in patients with CLDN18.2 positivity at initiation. Maintained CLDN18.2 positivity was more frequently observed in patients without MPR compared with those with MPR (53.8% v 12.5%, P = .05). Conclusion: HER2, PD-L1, and CLDN18.2 statuses were not linked to pathological response to FLOT in resectable GC/GEJC. CLDN18.2 expression significantly decreased after preoperative FLOT but remained higher in patients without MPR, suggesting that CLDN18.2-targeted therapy may warrant investigation in the perioperative setting.JCO Precision Oncology, 9, art. no. e2400925; 2025journal articl
Pemetrexed plus platinum as second-line treatment for patients with pleural mesothelioma treated with nivolumab plus ipilimumab
No full textThere is limited evidence regarding the second-line treatment for patients with unresectable, advanced, or metastatic pleural mesothelioma receiving first-line nivolumab plus ipilimumab combination immunotherapy. Although chemotherapy with pemetrexed and a platinum-based agent is empirically administered as the second-line treatment in clinical practice, its effect in patients after nivolumab plus ipilimumab remains unclear. Therefore, this retrospective observational study aimed to elucidate the efficacy of pemetrexed plus platinum therapy as a second-line treatment for pleural mesothelioma after first-line nivolumab-ipilimumab immunotherapy. Forty-three patients with unresectable or advanced pleural mesothelioma were enrolled in this study. Median overall survival was 17.1 months (95 % confidence interval [CI]: 9.3- not estimable), and median progression-free survival was 5.7 months (95 % CI: 3.9–11.9). The one-year overall survival rate was 62.8 % (95 % CI: 45.0–76.3) and one-year progression-free survival rate was 26.2 % (95 % CI: 10.4–45.2). In patients with measurable lesions, the overall response rate was 30.3 % and disease control rate was 69.7 %. These results are similar to those of previous studies on pemetrexed-platinum for pleural mesothelioma in first-line settings, suggesting that pemetrexed-platinum therapy can be considered an appropriate choice for the second-line treatment of mesothelioma after immunotherapy.Lung Cancer, 207, art. no. 108709; 2025journal articl
Chelation-based iron uptake mitigates the effects of prolonged high-temperature stress in cool-season grasses
Get PDFNature Communications, 16(1), art. no. 7709; 2025journal articl
Potential Effects of Grassland Restoration on the Water Resources in Nango-Dani, Aso, Japan
Get PDFThe semi-natural grasslands of the Aso Caldera, Japan, have historically played a key role in maintaining biodiversity, tourism, and water resources. However, they are now in decline due to a decrease in the number of agricultural workers and an aging workforce, as well as structural changes and stagnation in the agricultural and livestock industries. This study focused on the water resource maintenance function of grasslands by applying a water balance model to quantify the potential impact of grassland restoration on water resources in Nango-Dani, located in the southern part of the Aso Caldera. We simulated groundwater recharge, storage, spring discharge, and baseflow under multiple scenarios involving the conversion of coniferous trees to grasslands. According to the calculation results, replacing 10% of coniferous trees with grassland increased groundwater recharge by approximately 0.86 million m3. This increase is due to grasslands having a higher groundwater recharge capacity, owing to their higher canopy permeability and lower evapotranspiration. The storage volume increased by approximately 0.54 million m3, which is equivalent to the annual water usage of 6700 people. Furthermore, grassland restoration increased spring discharge and baseflow. These results quantitatively demonstrate a significant enhancement of regional water resource sustainability and provide scientific evidence to inform land-use policies.Water, 17(16), art. no. 2466; 2025journal articl
Valorization of agar extracted from Gelidium elegans via ultrasound-assisted extraction as potential film packaging by optimizing the incorporation of chitosan and curcumin
Get PDFThis study characterized agar extracted from Gelidium elegans using ultrasound-assisted extraction (UAE) compared with conventional extraction (CV). The CV yielded significantly higher agar (21.50 %) than UAE (17.91 %); however, both methods produced stable agar with high melting temperatures (90.00 °C and 86.67 °C) and low moisture content (MC) (12.06 % and 14.94 %), respectively. UAE agar exhibited higher gel strength (218.58 g·cm−2) and gelling temperature (36.00 °C), desirable color, and lower sulfate content (0.46 %). UAE agar was further applied to optimize agar-based composite films as alternatives toward plastic packaging by incorporating varying levels of chitosan (0.5–1.0 % w/v) and curcumin (0.04–0.10 % w/v). Film properties including water vapor permeability (WVP), oxygen permeability (OP), MC, solubility, transparency, and 2-diphenyl-1-picrylhydrazyl (DPPH) antioxidant activity were evaluated using response surface methodology–central composite design (RSM-CCD). The model was validated, and the optimum formulation was chosen based on highest desirability (0.9096) at 0.5 % (w/v) chitosan and 0.07 % (w/v) curcumin. The optimized film exhibited WVP (2.38 × 10−10 g/msPa), OP (4.28 × 10−7 g/ms), MC (13.71 %), solubility (29.19 %), transparency (9.93), and DPPH activity (60.77 %), all within specified prediction ranges. These findings demonstrate that agar-based composite films incorporating with chitosan and curcumin provides good validation of model prediction and hold strong potential for eco-friendly food packaging applications.International Journal of Biological Macromolecules, 327, art. no. 147323; 2025journal articl
Dabigatran‐induced esophagitis with full circumferential blue pigmentation
Get PDFDabigatran is a useful and widely used drug for stroke prevention in patients with atrial fibrillation. However, it has been reported to cause esophagitis. Herein, we report the case of a 77-year-old man with dabigatran-induced esophagitis with blue pigmentation, which is known to be a rare adverse effect. The patient presented to our hospital with a tightness of the chest and anorexia. Computed tomography revealed a thickening of the entire esophageal wall, with an upper esophageal predominance. Esophagogastroduodenoscopy was performed, which showed that the cervical and upper thoracic esophagus had blue pigmentation with edematous changes, partial narrowing, and longitudinal sloping. We replaced dabigatran with edoxaban, a similar anticoagulation medication. The patient was closely monitored for 1 month after switching to edoxaban. The follow-up esophagogastroduodenoscopy showed marked improvements, revealing resolution of the bluish discoloration and edematous changes, and the patient's complaints regarding the tightness of the chest and anorexia were also resolved. It is important to recognize that such side effects can occur with dabigatran, a drug that is frequently used in daily practice. Considering the fact that strong edematous changes can cause indigo carmine pigmentation associated with dabigatran stagnation, we recommend switching to another anticoagulant if esophagitis occurs during dabigatran administration.DEN Open, 4(1), art. no. e271; 2025journal articl