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Familial Mediterranean fever (FMF) is the most prevalent hereditary autoinflammatory disease and is caused by the MEFV gene. In patients carrying MEFV exon 10 variants, FMF usually develops at an early age. A 76-year-old Japanese man presented with a periodic fever lasting 2-3 days, chest pain, and abdominal pain. An MEFV gene analysis revealed compoundheterozygous M694I/E148Q/L110P. Colchicine treatment (0.5 mg/day) improved the patient's symptoms. This is the first case report of an elderly Japanese patient with FMF onset in the 70s carrying the MEFV exon 10 variant.

Developing high-performance and stable Sn-based perovskite solar cells (PSCs) is difficult due to the inherent tendency of Sn 2+ oxidation and, the huge energy mismatch between perovskite and Phenyl-C61-butyric acid methyl ester (PCBM), a frequently employed electron transport layer (ETL). This study demonstrates that perovskite surface defects can be passivated and PCBM's electrical properties improved by doping n-type polymer N2200 into PCBM. The doping of PCBM with N2200 results in enhanced band alignment and improved electrical properties of PCBM. The presence of electron-donating atoms such as S, and O in N2200, effectively coordinates with free Sn 2+ to prevent further oxidation. The doping of PCBM with N2200 offers a reduced conduction band offset (from 0.38 to 0.21 eV) at the interface between the ETL and perovskite. As a result, the N2200 doped PCBM-based PSCs show an enhanced open circuit voltage of 0.79 V with impressive power conversion efficiency (PCE) of 12.98% (certified PCE 11.95%). Significantly, the N2200 doped PCBM-based PSCs exhibited exceptional stability and retained above 90% of their initial PCE when subjected to continuous illumination at maximum power point tracking for 1000 h under one sun., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Objectives: We have proposed seven peptides with low molecular weights in blood as biomarkers for the diagnosis of hypertensive disorders of pregnancy (HDP). The purpose of this cross-sectional study was to investigate the relationships of the HDP-associated peptides with symptoms of leg ischemia and degree of atherosclerosis in patients with lower extremity arterial disease (LEAD). Methods: The subjects were 165 outpatients with LEAD (145 men and 20 women aged 74.3 ± 8.1 years [47-93 years]). Their symptoms of leg ischemia, leg arterial flow, and degree of atherosclerosis were evaluated using the Rutherford classification of Clinical Ischemia Category, ankle-brachial index (ABI) and the intima-media thickness (IMT) of carotid arteries, respectively. Serum concentrations of the HDP-related peptides were measured by mass spectrometry. Results: The grade of the Rutherford classification was positively associated with levels of the peptides with m/z 2091 and 2378 and was inversely associated with levels of the peptide with m/z 2081. The category of the Rutherford classification was inversely associated with ABI. There were no HDP-associated peptides that showed significant relationships with IMT. Conclusions: The peptides with m/z 2081, 2091, and 2378 are possible biomarkers of leg ischemia but are not associated with carotid atherosclerosis in LEAD patients., (@ 2024 The Editorial Committee of Annals of Vascular Diseases.)

The genetic lesions that drive acute megakaryoblastic leukemia (AMKL) have not been fully elucidated. To search for genetic alterations in AMKL, we performed targeted deep sequencing in 34 AMKL patient samples and 8 AMKL cell lines and detected frequent genetic mutations in the NOTCH pathway in addition to previously reported alterations in GATA-1 and the JAK-STAT pathway. Pharmacological and genetic NOTCH activation, but not inhibition, significantly suppressed AMKL cell proliferation in both in vitro and in vivo assays employing a patient-derived xenograft model. These results suggest that NOTCH inactivation underlies AMKL leukemogenesis. and NOTCH activation holds the potential for therapeutic application in AMKL., Competing Interests: Conflicts of Interest Disclosure The authors have nothing to disclose., (Copyright © 2024 International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.)

Background: Seven peptides with low molecular weights in blood have been identified as possible biomarkers of hypertensive disorders of pregnancy (HDP). A history of HDP is known to be associated with a high risk of cardiovascular disease in the later life of women with HDP. However, it remains to be determined whether HDP-related peptides are useful biomarkers of cardiovascular disease in the general population. The purpose of this study was to determine the relationships between these peptides and cardiometabolic risk in adult men., Methods: We investigated the relationships between HDP-related peptides and two recent indices of cardiometabolic risk, hematometabolic index (HMI) and lipid accumulation product (LAP), in male workers aged 35 to 69 years. Concentrations of the HDP-related seven peptides with mass/charge ratios ( m/z ) of 2081 (P-2081), 2091 (P-2091), 2127 (P-2127), 2209 (P-2209), 2378 (P-2378), 2858 (P-2858), and 3156 (P-3156) were measured simultaneously by using a mass spectrometer. Standardized partial regression coefficients (β) were obtained in multivariable linear regression analysis, and mean levels of the log-transformed HMI and LAP were compared in tertile groups of each peptide in the analysis of covariance with adjustment for age, habits of smoking and alcohol drinking, history of diabetes, and medication therapy for dyslipidemia., Results: There was a significant positive correlation between the HMI and the serum level of P-2378 (β = 0.310), a fragment of complement component 4, while a significant inverse correlation (β = -0.389) was obtained between the LAP and the serum level of P-3156, a fragment of inter-α-trypsin inhibitor heavy chain H4. Other peptides (P-2081, P-2091, P-2127, P-2209, and P-2858) did not show significant correlations with the HMI or LAP. The log-transformed HMI tended to be higher with an increase in the tertile for P-2378. The mean level of log-transformed LAP in the first tertile group of P-3156 was significantly higher than those in the second and third tertile groups of P-3156., Conclusion: The HDP-related peptides with m/z of 2378 and m/z of 3156 were shown to be associated with the HMI and LAP, respectively, which are recent indices reflecting cardiometabolic risk. Therefore, the peptides with m/z of 2378 and m/z of 3156 were thought to be potential biomarkers for discrimination of cardiovascular risk in adult men. Further studies on the relationships between the peptides and cardiovascular risk factors in non-pregnant women are needed to confirm the findings of this study., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Hyogo College of Medicine Ethics Committee issued approval No. 3449, on 18th February 2021. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: Japan Society for the Promotion of Science provided Grant-in-Aid for Scientific Research (No. 21H03386). Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Wakabayashi et al.)

A 55-year-old man developed ischemic stroke in the bilateral cerebellar hemispheres and bilateral occipital lobes. He was admitted to our hospital 17 months later with recurrent ischemic stroke in the posterior circulation. The left vertebral artery (VA) was occluded on brain magnetic resonance angiography but was visualized with a delay on continuous three-phase CT angiography (CTA). Conventional angiography confirmed a to-and-fro blood flow pattern at the distal end of the left VA, therefore the patient was diagnosed with VA stump syndrome (VASS). VASS is a recurrent posterior circulation ischemic stroke caused by thrombi in an occluded unilateral VA. VASS should be suspected in patients with unilateral VA occlusion and repeated posterior-circulation ischemic stroke. The diagnostic criteria for VASS include confirmation of VA occlusion and the presence of an antegrade flow component at the distal end. In this case, the presence of collateral circulation in the VA was suspected based on CTA findings, leading to the diagnosis of VASS. It was thus suggested that devising the imaging method of CTA may help diagnose VASS.

Background: Patients with cancer, particularly those undergoing chemotherapy, are at risk from the low immunogenicity of Coronavirus Disease 19 (COVID-19) vaccines., Methods: This prospective study assessed the seroconversion rate of COVID-19 vaccines among patients with cancer and hospital staff. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein-specific IgG (S-IgG) concentrations were evaluated before the first vaccination, and 1-3 and 4-6 months after the second vaccination. The primary endpoint was the seroconversion rate measured 1-3 months after the second vaccine., Results: In total, 590 patients and 183 healthy hospital staff were analyzed. At 1-3 months after the second vaccination, the S-IgG antibody concentration exceeded the cut-off value (20 BAU/mL) in 96.1% (567/590) of the patients with cancer and 100% (183/183) of the healthy controls (p = 0.0024). At 4-6 months after the second vaccination, the S-IgG antibody concentration exceeded the cut-off value (20 BAU/ml for S-IgG) in 93.1% (461/495) of the patients with cancer and 100% (170/170) of the healthy controls (p < 0.0001). Old age, being male, and low lymphocyte count were related to low SARS-CoV-2 S-IgG levels 1-3 months after the second vaccination among patients, while body mass index, smoking history, and serum albumin level were not. Patients undergoing platinum combination therapy and alkylating agent among cytotoxic drugs, and PARP inhibitor, mTOR inhibitor, and BCR-ABL inhibitor exhibited a low S-IgG antibody concentration compared to the no treatment group., Conclusions: COVID-19 vaccine immunogenicity was reduced among patients with cancer, especially under several treatment regimens., (© 2024. The Author(s).)

Glucose is the most important energy source in all organisms; however, our understanding of the pathways and mechanisms underlying glucose transportation and localization in living cells is incomplete. Here, we prepared two glucose analogs labeled with a dansylamino group at the C-1 (1-Dansyl) or C-2 (2-Dansyl) position; the dansyl group is a highly fluorescent moiety that is characterized by a large Stokes shift between its excitation and emission wavelengths. We then examined the cytotoxicity of the two glucose analogs in mammalian fibroblast cells and in the ciliated protozoan Tetrahymena thermophila. In both cell types, 2-Dansyl had no negative effects on cell growth. The specificity of cellular uptake of glucose analogs was confirmed using an inhibitor of glucose transporter in NIH3T3 cells. In NIH3T3 cells and T. thermophila, fluorescence microscopy revealed that the glucose analogs localized throughout the cytoplasm, but especially at the periphery of the nucleus. In T. thermophila, we also found that swimming speed was comparable in media containing non-labeled glucose or one of the glucose analogs, which provided more evidence not only that the analogs were not cytotoxic in these cells but also that the analogs had no negative effect on the ciliary motion. Together, the present results suggest that the glucose analogs have low toxicity and will be useful for bioimaging of glucose-related systems., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Society of Microscopy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Streptococcus salivarius is part of the normal oral cavity and gastrointestinal tract microflora and an unusual cause of acute bacterial meningitis. We herein report an 81-year-old man with S. salivarius meningitis, which led to a diagnosis of early esophageal cancer and early gastric cancer. S. salivarius infection may occur through the gastrointestinal mucosa when it is disrupted in association with early gastrointestinal cancer. To our knowledge, this is the first report describing S. salivarius meningitis associated with multiple early gastrointestinal cancers in the absence of other sources of infection.

Molecular passivation is a prominent approach for improving the performance and operation stability of halide perovskite solar cells (HPSCs). Herein, we reveal discernible effects of diammonium molecules with either an aryl or alkyl core onto Methylammonium-free perovskites. Piperazine dihydriodide (PZDI), characterized by an alkyl core-electron cloud-rich-NH terminal, proves effective in mitigating surface and bulk defects and modifying surface chemistry or interfacial energy band, ultimately leading to improved carrier extraction. Benefiting from superior PZDI passivation, the device achieves an impressive efficiency of 23.17% (area ~1 cm 2 ) (low open circuit voltage deficit ~0.327 V) along with superior operational stability. We achieve a certified efficiency of ~21.47% (area ~1.024 cm 2 ) for inverted HPSC. PZDI strengthens adhesion to the perovskite via -NH 2 I and Mulliken charge distribution. Device analysis corroborates that stronger bonding interaction attenuates the defect densities and suppresses ion migration. This work underscores the crucial role of bifunctional molecules with stronger surface adsorption in defect mitigation, setting the stage for the design of charge-regulated molecular passivation to enhance the performance and stability of HPSC., (© 2024. The Author(s).)

Background: NY-ESO-1 and XAGE1 cancer/testis antigens elicit humoral and cellular immune responses in NSCLC patients. We aimed to predict clinical benefit with ICI monotherapy, using an automated immunoassay of NY-ESO-1/XAGE1 antibodies (Abs)., Methods: This study enrolled 99 NSCLC patients who received nivolumab after chemotherapy, including 21 patients harboring EGFR, ALK, or KRAS alterations. The cutoff value (10 units/mL) of NY-ESO-1 and XAGE1 Ab was determined based on Ab levels in non-malignant controls, and NY-ESO-1/XAGE1 Abs in NSCLC were measured before nivolumab. Differences in PFS and OS between the Ab-positive and Ab-negative groups were retrospectively analyzed using Cox regression analysis after applying inverse probability of treatment weighting (IPTW)., Results: NY-ESO-1/XAGE1 Abs were positive in 28 NSCLC, who responded more highly to nivolumab than the Ab-negatives (response rate 50.0% vs. 15.5 %, p < 0.0007). The IPTW-adjusted positives and negatives for NY-ESO-1/XAGE1 Abs were 24.5 and 70.2, respectively. The Ab-positives showed longer IPTW-adjusted PFS (HR = 0.59, 95 % CI: 0.39-0.90, p = 0.014) and IPTW-adjusted OS (HR = 0.51, 95 % CI: 0.32-0.81, p = 0.004) than the Ab-negatives. Among NSCLC harboring driver genes, the Ab-positives (n = 10) showed longer PFS (HR = 0.34, 95 % CI: 0.13-0.89, p = 0.029) and OS (HR = 0.27, 95 % CI: 0.098-0.75, p = 0.012) than the Ab-negatives (n = 11)., Conclusion: Our immunoassay of NY-ESO-1/XAGE1 Abs is probably useful for predicting the clinical benefit with nivolumab in NSCLC, including those harboring driver genes. These results suggest that our immunoassay may be useful in ICI monotherapy for NSCLC., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kanako Sakaeda, Yasuhiro Irino, and Masatoshi Yanagida received personal fees for salary as full-time employees and stock ownership from Sysmex corporation. Satoshi Muto had grants or contracts from JSPS KAKENHI; received payment or honoraria for lectures or manuscript writing from MSD, AstraZeneca, Eli Lilly Japan, Bristol Myers Squibb, Tahiho Pharmaceutical, Chugai Pharmaceutical and “Gan to Kagakuryoho”. Takeshi Masuda received payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Daiichi-Sankyo, Nippon Boehringer Ingelheim, Ono Pharmaceutical, Otsuka Pharmaceutical, AstraZeneca, Taiho Pharmaceutical, Kyowa Kirin, Eli Lilly Japan and Chugai Pharmaceutical. Yumiko Sakai and Yusuke Atarashi received personal fees for salary as full-time employees. Noboru Hattori received payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Chugai Pharmaceutical, Ono Pharmaceutical, AstraZeneca, Bristol Myers Squibb and MSD. Mikio Oka and Koji Kurose received JSPS KAKENHI Grant, Collaborative Research Fund from Sysmex Corporation and Endowment from Pole Star. The other authors have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)