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IgLON5 autoimmunity is characterized by a diverse range of clinical presentations, including neuropsychiatric symptoms, sleep disturbances, gait instability, and bulbar symptoms, that are usually insidiously progressive. While some individuals with specific HLA haplotypes may be more susceptible to developing anti-IgLON5 disease, this antibody is typically not associated with a paraneoplastic etiology nor known to be induced by immune checkpoint inhibitors (ICI). We present a clinical and serological workup of a patient who developed symptoms of IgLON5 autoimmunity following treatment with pembrolizumab. He was found to have IgLON5 antibodies present in both the serum and cerebrospinal fluid, but he also expressed high-risk HLA haplotypes. This case suggests that immune checkpoint inhibitors (ICI) may promote the development of IgLON5 autoimmunity, particularly in those with high-risk HLA haplotyes., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Benzoate-bridged paddlewheel diruthenium(II,II) complexes ([RuII,II2(R n ArCO 2 ) 4 (L ax ) 2 ] (L ax = axial ligand); [RuII,II2]) exhibit reversible redox activity involving the oxidized species [RuII,III2] + . The redox activity can be finely tuned over a broad potential range by altering the substituent R on the benzoate-bridging ligand R n ArCO 2 - . The electronic contributions of the substituents R depend on their type and position, as was empirically demonstrated by Hammett for substituents at the meta - and para -positions. However, the substituent effect at the ortho -position is not solely determined by the electronic contribution of R but also by steric hindrance between the o -substituents and adjacent carboxylate groups. Nevertheless, an OH group at the o -position did not provide any steric hindrance, leading to a strong electron-withdrawing effect owing to intramolecular hydrogen bonding between the o -OH group and the adjacent carboxylate group, despite the electron-donating ability of the m - and p -OH groups. The OH group at the o -position induced a significant shift in the redox potential and HOMO energy levels of the [RuII,II2] complexes, thereby stabilizing the [RuII,II2] state. The redox potential and HOMO can be adjusted by introducing additional substituents, such as F, Cl, Me, OMe, and CF 3 groups, to cover a wide range, in accordance with an extended Hammett law that considers the contribution of the o -position.

The paddlewheel-type dimetal core ([M 2 ]) is a ubiquitous motif in the nodes in coordination polymers (CPs) and metal-organic frameworks (MOFs). However, their preparation has relied on ligand-substitution-labile metal ions owing to challenges associated with crystallization. Consequently, examples featuring ligand-substitution-inert metal ions, such as Ru or Rh, are scarce. This study presents the synthesis of novel reticular imine-linked CPs incorporating the paddlewheel-type diruthenium(II, II) ([Ru 2 II,II ]; 1-Ru) or dirhodium(II, II) ([Rh 2 II,II ]; 1-Rh) subunits. The synthetic approach involved a Schiff base dehydration condensation reaction between p-formylbenzoate-bridged [Ru 2 II,II ] or [Rh 2 II,II ] precursors (i. e., CHO-Ru and CHO-Rh, respectively) and 2,5-dimethyl-1,4-phenylenediamine in a 1 : 2 ratio. The catalytic activities of 1-Ru and 1-Rh for the photochemical reduction of CO 2 in a heterogeneous system depended on the metal site. The 1-Ru system exhibited exceptional selectivity, generating 3.0×10 4  μmol g -1 of CO after 24 h of irradiation, whereas the 1-Rh system generated a lower amount of CO (3.2×10 3  μmol g -1 ). The catalytic activity of 1-Ru ranked with that of all relevant catalytic systems. This study paves the way for the exploration of [Ru 2 II,II ]- or [Rh 2 II,II ]-based polymers with open metal site-dependent functional properties., (© 2024 The Authors. ChemSusChem published by Wiley-VCH GmbH.)

Introduction/aims: Duchenne muscular dystrophy (DMD) presents with skeletal muscle weakness, followed by cardiorespiratory involvement. The need for longitudinal data regarding DMD that could serve as a control for determining treatment efficacy in clinical trials has increased notably. The present study examined the longitudinal data of Japanese DMD patients collectively and assessed individual patients with pathogenic variants eligible for exon-skipping therapy., Methods: Patients with DMD who visited Kobe University Hospital between March 1991 and March 2019 were enrolled. Data between the patients' first visit until age 20 years were examined., Results: Three hundred thirty-seven patients were included. Serum creatine kinase levels showed extremely high values until the age of 6 years and a rapid decline from ages 7-12 years. Both the median 10-m run/walk velocity and rise-from-floor velocity peaked at the age of 4 years and declined with age. The values for respiratory function declined from the age of 11 years. The median left ventricular ejection fraction was >60% until the age of 12 years and rapidly declined from ages 13-15 years. Examination of the relationship between pathogenic variants eligible for exon-skipping therapy and longitudinal data revealed no characteristic findings., Discussion: We found that creatine kinase levels and motor, respiratory, and cardiac functions each exhibited various changes over time. These findings provide useful information about the longitudinal data of several outcome measures for patients with DMD not receiving corticosteroids. These data may serve as historical controls in comparing the natural history of DMD patients not on regular steroid use in appropriate clinical trials., (© 2024 Wiley Periodicals LLC.)

A new synthetic route for constructing functional paddlewheel diruthenium(II,II) complexes ([RuII,II2]) was developed by utilizing Schiff base condensation reactions of formyl-substituted benzoate-bridged [RuII,II2] complexes with various aromatic monoamines under mild conditions. Cyclic voltammetry and DFT calculations revealed that the attached Schiff base groups significantly affected the electronic states of the resulting [RuII,II2] complexes.

Background: The most recommended treatment for stage IV EGFR-positive lung cancer is osimertinib monotherapy. The dosage of osimertinib is fixed at 80 mg/day regardless of body surface area (BSA), however some patients withdraw or reduce the dosage due to adverse events (AEs)., Methods: We performed a retrospective cohort study of 98 patients with EGFR mutation-positive non-small cell lung cancer (NSCLC), who received 80 mg osimertinib as the initial treatment. We investigated the impact of BSA on efficacy and safety of osimertinib., Results: The cut-off value of BSA was estimated using the receiver operating characteristics curve, and was determined to be 1.5 m 2 . There were 44 patients in the BSA < 1.5 group and 54 patients in the BSA ≥ 1.5 group. There was no significant difference in the incidence of AEs (hematologic toxicity of ≥grade 3 or higher, and non-hematologic toxicity of ≥grade 3) between the two groups. However, the incidence of dose reduction due to AEs was significantly higher in the BSA < 1.5 group compared with the BSA ≥ 1.5 group (16 patients vs 5 patients, p = 0.003). The main reasons were fatigue, anorexia, diarrhea, and liver disfunction. Median progression-free survival (PFS) was not significantly different (16.9 months in the BSA < 1.5 group vs 18.1 months in the BSA ≥ 1.5 group, p = 0.869)., Conclusion: Differences in BSA affected the optimal dose of osimertinib. However, the PFS with osimertinib treatment was not affected by BSA. Therefore, when using osimertinib as an initial treatment for patients with EGFR-mutant NSCLC, dose reduction to control AEs should be considered, especially in the BSA<1.5 group., Competing Interests: Declaration of competing interest Motohiro Tamiya has received lecture fees from Chugai Pharmaceutical, Boehringer Ingelheim, AstraZeneca, Taiho Pharmaceutical, Eli Lilly, Novartis, Pfizer, Asahi Kasei Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb, MSD, Bayer, Amgen, Kyowa-Kirin, and Nippon Kayaku. Kei Kunimasa has received lecture fees from AstraZeneca, Chugai Pharma and Novartis. Kazumi Nishino has received lecture fees from AstraZeneca, Chugai Pharmaceutical, Boehringer Ingelheim, Eli Lilly, Roche Diagnostics, Novartis, Pfizer, Merk, Janssen Pharmaceutical K.K., Bristol Myers Squibb, and Nippon Kayaku. Mari Takagi has received lecture fees from Eli Lilly, Yakult, Terumo, Chugai Pharmaceutical, Towa Pharmaceutical, Daiichi-Sankyo, Becton Dickinson and Company, MSD, Taiho Pharmaceutical, Nippon Kayaku, AstraZeneca, Sando, and Ono Pharmaceutical. Other authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier Ltd.)

Evaluation of rapidly progressive dementia (RPD) is usually challenging. In most cases, patients progress to dementia in weeks to months, and the differential diagnosis is broad. In this case, a woman in her 60s presented with a 1-month history of episodic vertigo, cognitive decline, ataxia and myoclonus. Cerebrospinal fluid total tau was markedly elevated, which was helpful in establishing the diagnosis and discussing prognosis/end-of-life measures with the patient's family. This case summarises a stepwise diagnostic approach for patients with RPD and highlights recent literature on biomarkers of Creutzfeldt-Jakob disease and autoimmune encephalitis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Fast ions play a crucial role in plasma heating, and their behavior in the plasma must be accurately understood. A diagnostics method based on charge exchange emission from the n = 4 - 3 transition (λ0 = 468.6 nm) of energetic 3He produced by the deuteron-deuteron reaction has been proposed as a for fast deuterons with energies in the order of MeV. The proposed method has the following advantages: No beam emission interferes with the spectra, the direction of the measuring line of sight, and the injection angle of the diagnostic beam can be freely determined. In previous studies, due to competing bremsstrahlung, it was expected that the proposed method will not be practical in the case of high electron density operation. This paper makes the proposed method available for measurement even at high electron densities by optimizing the measurement line of sight direction and the diagnostic beam incidence angle. This allows an electron density five times larger than the range of applications shown in previous studies. This result will contribute to measure of DT alpha in ITER., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

Background/aim: Shear wave measurement (SWM) is a new elastography modality that quantifies the shear wave velocity (Vs) and the percentage of the net effective shear wave velocity (VsN). This study examined whether these parameters could be used to differentiate between malignant and benign thyroid tumors., Patients and Methods: The study of SWM enrolled 111 patients (133 nodules) who underwent thyroid surgery. Overall, 61 nodules were diagnosed as benign and 72 as malignant, of which 68 nodules were diagnosed as papillary thyroid carcinoma (PTC) and 4 as follicular thyroid carcinoma (FTC)., Results: A preoperative SWM revealed that Vs was significantly higher and VsN significantly lower in the PTC compared to the benign nodules. The VsN of FTC was significantly lower than that of follicular adenoma. Multivariate analysis revealed that VsN significantly correlated with nodule malignancy., Conclusion: SWM parameters, especially VsN, can potentially differentiate between benign and malignant thyroid nodules non-invasively., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Transhepatic placement of a metallic biliary stent for internal drainage of persistent liver abscesses was performed in 9 patients (males; median age, 65 years; range, 57-82 years) with refractory liver abscess. The median follow-up period was 2.8 months (range, 0.4-50.3 months). Technical success was achieved in all cases without any major complications. Clinical success, defined as the removal of the drainage tube without recurrent symptoms of infection, was achieved in 8 cases. Median duration until removal of the drainage tube from stent placement was 7 days (range, 0-36)., (Copyright © 2020 SIR. Published by Elsevier Inc. All rights reserved.)

A two-dimensional nanocarbon, graphene, has attracted substantial interest due to its excellent properties. The reduction of graphene oxide (GO) has been investigated for the mass production of graphene used in practical applications. Different reduction processes produce different properties in graphene, affecting the performance of the final materials or devices. Therefore, an understanding of the mechanisms of GO reduction is important for controlling the properties of functional two-dimensional systems. Here, we determined the average structure of reduced GO prepared via heating and photoexcitation and clearly distinguished their reduction mechanisms using ultrafast time-resolved electron diffraction, time-resolved infrared vibrational spectroscopy, and time-dependent density functional theory calculations. The oxygen atoms of epoxy groups are selectively removed from the basal plane of GO by photoexcitation (photon mode), in stark contrast to the behavior observed for the thermal reduction of hydroxyl and epoxy groups (thermal mode). The difference originates from the selective excitation of epoxy bonds via an electronic transition due to their antibonding character. This work will enable the preparation of the optimum GO for the intended applications and expands the application scope of two-dimensional systems.

Introduction: Few long-term cohort studies have addressed changes in the ambulatory capacity of patients with Duchenne muscular dystrophy (DMD), and no reports have evaluated the factors associated with ambulatory capacity in Japanese., Methods: The longitudinal changes in 10-meter run/walk ability and associated factors were retrospectively investigated using general practice data. The factors associated with loss of this ability before the age of 10 years were explored by logistic regression analysis using parameters of genetic mutations, corticosteroid use, the manual muscle test (MMT), and the joint range of motion (ROM). Explanatory variables of MMT grade included hip flexors, knee flexors, and knee extensors; ROM included hip extension, knee extension, and ankle dorsiflexion., Results: Among 418 patients diagnosed with DMD, 145 patients underwent the 10-meter run/walk test between March 1999 and July 2015. The median age at loss of 10-meter walking ability was 10.4 (interquartile range: 9.2-11.3) years. The 10-meter run/walk speed began to decline 3 years before the loss of 10-meter walking ability, and the median was <1 m/s 1 year before the loss of 10-meter walking ability. MMT grade for knee flexors and ROM for hip and knee extension were identified as independent predictors. Based on the change over time of these three items, limitation of the hip extension ROM preceded knee flexor weakness and limitation of the knee extension ROM., Conclusions: This knowledge can be used in optimizing rehabilitation programs and evaluating effect of treatment for DMD patients., (Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: We comprehensively analyzed X-ray cocrystal structures of dipeptidyl peptidase IV (DPP-4) and its inhibitor to clarify whether DPP-4 alters its general or partial structure according to the inhibitor used and whether DPP-4 has a common rule for inhibitor binding., Results: All the main and side chains in the inhibitor binding area were minimally altered, except for a few side chains, despite binding to inhibitors of various shapes. Some residues (Arg125, Glu205, Glu206, Tyr662 and Asn710) in the area had binding modes to fix a specific atom of inhibitor to a particular spatial position in DPP-4. We found two specific water molecules that were common to 92 DPP-4 structures. The two water molecules were close to many inhibitors, and seemed to play two roles: maintaining the orientation of the Glu205 and Glu206 side chains through a network via the water molecules, and arranging the inhibitor appropriately at the S2 subsite., Conclusions: Our study based on high-quality resources may provide a necessary minimum consensus to help in the discovery of a novel DPP-4 inhibitor that is commercially useful.

Dietary fiber intake provides various physiological and metabolic effects for human health. Pectin, a water-soluble dietary fiber, induces morphological changes of the small intestine in vivo. However, the molecular mechanisms underlying pectin-derived morphological alterations have not been elucidated. Previously, we found that pectin purified from Prunus domestica L. altered the sulfated structure of cell-surface heparan sulfate (HS) on differentiated Caco-2 cells via fibronectin and α5β1 integrin. In this study, we investigated the biological significance of the effect of pectin on HS in differentiated Caco-2 cells. An in vitro intestinal epithelium model was constructed by co-culture of differentiated Caco-2 cells and rat IEC-6 cells, which were used as models of intestinal epithelium and intestinal crypt cells, respectively. We found that pectin-treated differentiated Caco-2 cells promoted growth of IEC-6 cells. Real-time RT-PCR analysis and western blotting showed that relative mRNA and protein expression levels of Wnt3a were upregulated by pectin treatment in differentiated Caco-2 cells. Analysis by surface plasmon resonance spectroscopy demonstrated that pectin-induced structural alteration of HS markedly decreased the interaction with Wnt3a. However, depression in the secretion of Wnt3a from Caco-2 cells by anti-Wnt3a antibody did not affect the proliferation of IEC-6 cells in co-culture system. These observations indicated that pectin altered the sulfated structure of cell-surface HS to promote secretion of Wnt3a from differentiated Caco-2 cells and Wnt3a indirectly stimulated the proliferation of IEC-6 cells.