Search

Hexagonal shaped nanoparticles about 60 nm in size were successfully synthesized in tetraethylene glycol solution containing polyvinylpyrrolidone. By the analysis of the electron diffraction pattern, these were identified as a single crystal of Ni carbide with Ni3C − type structure. Their magnetization curve at 5 K was not completely saturated under a magnetic field of 5 T. The thermomagnetization curves after zero-field cooling and after field cooling exhibited the magnetic cooling effect at low temperatures. Furthermore, the 2nd order nonlinear term of AC magnetic susceptibility exhibited a negative divergence at about 17 K. It is concluded that Ni carbide single crystal nanoparticles with the Ni3C − type structure exhibit spin-glass transition at low temperatures.

Native chickens (Gallus domesticus) of Bangladesh are scavenging in nature. Data regarding morphology of lymphoid organs in prenatal stages are lacking. H&E staining method was performed to study the development of the bursa of Fabricius, thymus, spleen and cecal tonsil from embryonic day (ED) 10 to 20. The budding of thymus was seen on ED 10. At ED 12, fiber network of thymus was formed to create a basement of cells of thymus and on ED 14 these cells began to organize to form cortex and medulla. But the cortex and medulla of thymus could not be differentiated before ED 20. The plicae of bursa Fabricius started to develop on ED 10. From ED 12 the plicae became shorter and wider to form bursal follicles and these follicles were clearly organized into cortex and medulla on ED 20. At ED 10, very thin capsule was seen in embryonic spleen. During ED 12, only a few white pulps were observed, while on ED 14, purple colored white pulp and pinkish red pulp were easily visible. At ED 20, the thickness of capsule was increased and pulps were more distinguishable. All the lymphoid organs showed major development during the later incubation period, indicating that the immune system in that period is being prepared to face the scavenging environment after hatching.

Abstract  Subtle variations of frequencies in the infrared (IR) absorption spectra of beryl have been predicted based on the coordination between extra-framework cations and water molecules in two orientations (referred to as type I and type II) trapped within the channel. In this study, the polarized IR spectra of hydrated synthetic beryl and natural beryl were measured to clarify the relationships between the frequencies of the absorption bands and the coordination states of type II water. Na+ was assumed to be the predominant cation coordinated to type II water in our samples, as determined by chemical analyses. These measurements revealed a clear quantitative linear relationship in absorbance between bands at 3,602 and 1,619 and at 3,589 and 1,631 cm−1. On the basis of experimental and theoretical studies, we assigned these pairs of bands to the ν1 and ν2 modes of doubly coordinated type II H2O and to singly coordinated type II H2O, respectively. These assignments were supported by IR measurements of annealed natural beryl. We also conducted dehydration studies of natural beryl, in which two observed dehydration peaks, at 600 and 750°C, suggested the dehydration of type I and type II water, respectively. [ABSTRACT FROM AUTHOR]

Nanocrystalline Ni0.5Zn0.5Fe2O4spinel ferrite with a grain size of 50?nm was prepared by using the ceramic method. The grain size was further reduced to 14?nm by milling the as-prepared ferrite particles in a high-energy ball mill. From the impedance spectroscopy studies we have observed that the dc electrical conductivity increases upon milling. Furthermore, the cation distribution data, as obtained from the in-field Mössbauer and extended x-ray absorption fine structure measurements, suggested a decrease in the conductivity for the milled sample. The increase in conductivity of the milled sample is, therefore, attributed to conduction by the oxygen vacancies created by mechanical milling. The higher values obtained for the activation energy for conduction are also evidence for the oxygen vacancy conduction. The increase in Néel temperature from 573 to 611?K on reducing the grain size from 50 to 14?nm has been explained based on the changes in the cation distribution. The observed increase in the coercivity of the milled sample has been attributed to surface anisotropy of increasing number of ions on the surface. The Mössbauer spectra show canted spin structure for the milled samples. [ABSTRACT FROM AUTHOR]

We quantitatively estimated the optical-coupling efficiency at the InGaAlAs-InGaAsP butt-joint (BJ) part by fabricating a novel multiple-butt-jointed (MBJ) laser. The lasing characteristics of InGaAlAs-InGaAsP MBJ lasers formed by in situ cleaning process showed a high optical-coupling efficiency of approximately 98%, which is comparable to that of a conventional InGaAsP-InGaAsP MBJ lasers. Thus, high-quality BJ-based heterointegration of InGaAlAs and InGaAsP was successfully demonstrated. [ABSTRACT FROM PUBLISHER]

The demand for precisely controlled etching is increasing as semiconductor device geometries continue to shrink. To fulfill this demand, cyclic atomic level/layer etching will become one of the key technologies in semiconductor device manufacturing at nanometer dimensions. This review describes recent trends in semiconductor devices and some of the latest results on cyclic atomic-level etching. In particular, it focuses on two types of cyclic etching that use different heating procedures: infrared irradiation for isotropic etching and Ar+ ion bombardment for anisotropic etching. It describes how an inductively-coupled-plasma down-flow etching apparatus with infrared lamps can be used for isotropic cyclic etching. The isotropic cyclic etching of SiN involves the formation and thermal desorption of ammonium hexafluorosilicate-based surface modified layers. This method features high selectivity with respect to SiO2, atomic-level control of the amount of SiN etching, and isotropic etched features. On the other hand, the anisotropic cyclic etching with Ar+ ion bombardment uses a microwave electron-cyclotron-resonance plasma etching apparatus. The anisotropic process for poly Si is composed of cyclic repetitions of chlorine adsorption and Ar+ ion bombardment. The anisotropic process for SiN is composed of cyclic repetitions involving an adsorption step using hydrofluorocarbon chemistry and a desorption step using Ar+ ion bombardment. Potential applications of these isotropic/anisotropic cyclic etching processes are described. [ABSTRACT FROM AUTHOR]

Purpose: To assess the real-world outcome of best-corrected visual acuity after 2-year intervention for treatment-naive diabetic macular edema since the approval of anti-vascular endothelial growth factor therapy., Methods: A total of 1,780 treatment-naive eyes with diabetic macular edema for which intervention was initiated between 2015 and 2019, and which were followed for 2 years, were extracted from the longitudinal medical records of 37 retinal disease institutions in Japan. Interventions included anti-VEGF therapy, topical corticosteroid therapy, macular photocoagulation, and vitrectomy. The baseline and final best-corrected visual acuity, and the number and timing of interventions were recorded. Eyes were classified according to the year in which intervention was initiated., Results: Over a 2-year period, best-corrected visual acuity improved annually, finally reaching seven letters. The proportion of eyes in which good vision was maintained (best-corrected visual acuity >20/40) increased to 73.3% in the latest period. The administration of anti-VEGF therapy remained stable, accounting for approximately 90% of eyes. Notably, the proportion of eyes receiving anti-VEGF drugs as first-line treatment increased dramatically to approximately 80%., Conclusion: Anti-VEGF therapy has become the first-line treatment since the approval of anti-VEGF drugs for diabetic macular edema. These findings reflect the evolution of diabetic macular edema treatment and highlight the superiority of anti-VEGF therapy and its increased uptake over time., Competing Interests: The authors declare no conflicts of interest in association with the present study., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Huntingtin-associated protein 1 (HAP1) is an essential constituent of the stigmoid body (STB) and is known as a neuroprotective interactor with causal agents for several neurodegenerative disorders, including huntingtin (HTT) in Huntington's disease. Previous in vitro studies showed that compared to normal HTT, STB/HAP1 exhibited a higher binding affinity for mutant HTT. The detailed in vivo relationships of STB/HAP1 with endogenous HTT, however, have not been clarified yet. This study examined the distribution of endogenous HTT and its relationships with STB/HAP1 in the adult mouse brain and spinal cord using light/fluorescence microscopy. Our results show that HTT immunoreactivity is highly distributed in the striatum, medial septal nucleus (MS), nucleus of the horizontal limb/ vertical limb of the diagonal band of Broca (HDB, VDB), substantia innominata basal part (SIB), pedunculopontine tegmental nucleus (PPTg), laterodorsal tegmental nucleus (LDTg), autonomic preganglionic neurons, and brainstem/spinal motoneurons. More than 90 % of HTT-immunoreactive (ir) neurons contain STB/HAP1 immunoreactivity in MS, VBD/HDB, SIB, PPTg, LDTg, and autonomic preganglionic nuclei. HTT-ir neurons in the striatal and motor nuclei, however, do not exhibit HAP1 immunoreactivity. These suggest that due to the absence of STB/HAP1-protectivity, HTT-ir striatal/motor neurons are more vulnerable to neurodegeneration than other HAP1-expressing HTT neurons. Our current findings might provide a framework for elucidating the pathophysiological functions of endogenous HTT and HAP1 in the central nervous system., Competing Interests: Declaration of Competing Interest The authors state that any known competing financial interests or personal relationships could have influenced none of the work described in this study., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: This study aimed to describe a novel technique of direct anterior chamber (AC) air replacement (DACAR) for the management of Descemet stripping automated endothelial keratoplasty (DSAEK) in postvitrectomized eyes and eyes with previous glaucoma surgery., Methods: DACAR was performed after a corneal donor graft was transplanted through a wound using the pull-through technique. DACAR involves stabilizing the graft with forceps while introducing air into the AC via an infusion cannula to ensure complete air exchange. The air was maintained in the AC at all times using a vitrectomy machine. The air pressure was maintained at 30 mm Hg for 15 minutes., Results: The DACAR technique was performed in 34 patients, and conventional pull-through technique DSAEK was performed in 32 high-risk patients. The DACAR group had shorter DSAEK surgical procedures (P = 0.009) and a lower incidence of corneal graft detachment in the early postoperative period (P < 0.001) than the conventional DSAEK group., Conclusions: DACAR is performed in patients having previously undergone vitrectomy or glaucoma surgery to prevent corneal graft detachment during the early postoperative period and to reduce the length of surgery., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: This study evaluates the effect of 6° horizontal gaze tolerance on visual field mean sensitivity (MS) in patients with glaucoma using a binocular head-mounted automated perimeter, following findings of structural changes in the posterior globe from magnetic resonance imaging and optical coherence tomography., Methods: In this cross-sectional study, a total of 161 eyes (85 primary open-angle glaucoma [POAG] and 76 healthy) from 117 participants were included. Logistic regression and 1:1 matched analysis assessed the propensity score for glaucoma and healthy eyes, considering age, sex, and axial length as confounders. Visual field tests were performed with the imo perimeter (CREWT Medical Systems, Inc., Tokyo, Japan) at central gaze, 6° abduction, and 6° adduction positions as fixation points. A mixed-effects model was used to compare MS under all conditions., Results: The analysis included a total of 82 eyes, with 41 POAG and 41 healthy after matching. The mean (standard deviation) age was 68.0 (11.0) years, with a mean deviation of -9.9 (6.6) dB for POAG and -1.0 (1.9) dB for healthy eyes using Humphrey field analysis 24-2. MS did not significantly differ among central gaze (27.0 [1.8] dB), abduction (27.1 [1.9] dB), and adduction (26.9 [2.2] dB) in healthy eyes (P = 0.650). However, MS was significantly lower for adduction (17.2 [5.9] dB) compared to central gaze (18.1 [5.9] dB) and abduction (17.9 [5.9] dB) in glaucoma eyes (P = 0.001 and P = 0.022, respectively)., Conclusions: Horizontal gaze, especially in adduction, significantly reduces visual sensitivity in glaucoma, suggesting a specific vulnerability associated with eye movement. This finding highlights the importance of eye positioning in glaucoma, warranting further investigation of its clinical significance.

Although physical stability can be a critical issue during the development of amorphous solid dispersions (ASDs), there are no established protocols to predict/detect their physical stability. In this study, we have prepared fenofibrate ASDs using two representative manufacturing methods, hot-melt extrusion and spray-drying, to investigate their physical stability for one year. Intentionally unstable ASDs were designed to compare the detection power of each evaluation method, including X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and dissolution study. Each method did not provide the same judgment results on physical stability in some cases because of their different evaluation principles and sensitivity, which has been well-comprehended only for one-component glass. This study revealed that the detection powers of each evaluation method significantly depended on the manufacturing methods. DSC was an effective method to detect a small amount of crystals for both types of ASDs in a quantitative manner. Although the sensitivity of XRPD was always lower compared to that of DSC, interpretation of the data was the easiest. SEM was very effective for observing the crystallization of the small amount of drug for hot-melt extruded products, as the drug crystal vividly appeared on the large grains. The dissolution performance of spray-dried products could change even without any indication of physical change including crystallization. The advantage/disadvantage and complemental roles of each evaluation method are discussed for deeper understanding on the physical stability data of ASDs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Purpose: We describe the clinical findings in a Japanese patient with unilateral traumatic optic neuropathy (TON) who underwent steroid pulse therapy followed by optic canal decompression surgery. The optic nerve function was assessed longitudinally and quantitatively by Goldmann visual fields (GVFs). This was accomplished by measuring the area of each isopter and scotoma, and the findings were compared with the visual acuities recorded during the course of the resolution of the TON. Case Presentation: A 70-year-old man suffered from TON in his left eye after falling from a 3 m cliff. On examination at the Saitama Medical University Hospital, his decimal best corrected visual acuity (BCVA) in his left eye was 0.2. Computed tomography revealed a fracture of the lateral wall of the left orbit, but no obvious optic canal fracture was observed. Steroid pulse therapy was started, and optic nerve decompression surgery was performed. After steroid administration, there was a slight improvement in the visual acuity, and a response in the I/3e isopter was present (area 17.76 deg 2 ). However, the V/4e area decreased from 539.35 to 359.36 deg 2 . Three days after the optic canal decompression surgery, the decimal visual acuity improved to 0.6, and the V/4e area and I/3e area increased to 1122.52 and 46.88 deg 2 , respectively. Postoperatively, there was a marked improvement in the size of the GVFs that corresponded to the improved visual acuity. The visual acuity of the left eye was 0.8 after 6 months, and the GVF was still not completely normal. Conclusions: Our findings showed the course of recovery of the visual acuity and visual field in an eye with TON. The quantification of GVF was helpful in assessing the course of recovery after the treatments. The new quantitative index of the GVFs may be helpful in evaluating the effectiveness of treatments for optic nerve disorders., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Midori Tachibana et al.)

Kusaya shows a high preservability due to the microorganism-derived antibiotics contained in kusaya gravy, which is important for kusaya manufacturing. However, the antimicrobial compounds and its producing bacteria, as well as the antimicrobial activity of the kusaya gravy itself, have remained unknown. In this study, we isolated antibiotic-producing bacteria of the genus Streptomyces from kusaya gravy from Hachijojima and found that they produced antibacterial substances against various fungi and bacteria. In addition, we demonstrated that kusaya gravy itself shows antimicrobial activity, which was consistent with that of the isolates. This is the first report to directly indicate that kusaya gravy contains microorganism-derived antibiotics, which are assumed to be produced by actinomycetes.

Purpose: To report a case of lacrimal drainage pathway disease-associated keratopathy (LDAK) with endophthalmitis., Observations: An 80-year-old man with diabetic retinopathy and nephropathy was referred to our hospital with endophthalmitis of the left eye. Slit-lamp examination revealed slight eye discharge, peripheral corneal ulcers, diffuse hyperemia of the conjunctiva, iris synechia, and a large amount of fibrin in the anterior chamber of the left eye. No puncta of the left eye were observed. The patient had undergone trabeculectomy for primary open-angle glaucoma 5 years previously. B-mode echo examination confirmed vitreous opacity in the left eye. We suspected endophthalmitis and performed a par-plana vitrectomy, bacterial culture, and polymerase chain reaction examination for eye discharge, aqueous humor, and vitreous humor. However, no bacteria or viruses were detected. The eye discharge and corneal peripheral ulcers did not improve following surgery. A lacrimal syringe test was performed two weeks after surgery, and bacterial concretion and discharge were observed. We detected Actinomyces in the bacterial concretions and performed dacryocystorhinostomy. After surgery, the corneal ulcer improved, and eye discharge disappeared., Conclusions and Importance: LDAK causes corneal perforation and endophthalmitis. In cases of intraocular inflammation with corneal ulcers, a lacrimal syringing test should be performed, even in the absence of lacrimal findings on slit-lamp examination., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors have no conflict of interest., (© 2024 The Authors.)

Patient respiration is characterized by respiratory parameters, such as cycle, amplitude, and baseline drift. In treatment planning using four-dimensional computed tomography (4DCT) images, the target dose may be affected by variations in image reconstruction techniques and respiratory parameters. This study aimed to optimize 4DCT image reconstruction techniques for the treatment planning of lung stereotactic body radiotherapy (SBRT) based on respiratory parameters using respiratory motion phantom. We quantified respiratory parameters using 30 respiratory motion datasets. The 4DCT images were acquired, and the phase- and amplitude-based reconstruction images (RI) were created. The target dose was calculated based on these reconstructed images. Statistical analysis was performed using Pearson's correlation coefficient (r) to determine the relationship between respiratory parameters and target dose in each reconstructed technique and respiratory region. In the inhalation region of phase-based RI, r of the target dose and baseline drift was -0.52. In particular, the target dose was significantly reduced for respiratory parameters with a baseline drift of 0.8 mm/s and above. No other respiratory parameters or respiratory regions were significantly correlated with target dose in phase-based RI. In amplitude-based RI, there were no significant differences in the correlation between all respiratory parameters and target dose in the exhalation or inhalation regions. These results showed that the target dose of the amplitude-based RI did not depend on changes in respiratory parameters or respiratory regions, compared to the phase-based RI. However, it is possible to guarantee the target dose by considering respiratory parameters during the inhalation region of the phase-based RI., (© 2024. The Author(s), under exclusive licence to Japanese Society of Radiological Technology and Japan Society of Medical Physics.)

Soluble epoxide hydrolase (sEH) is a bifunctional enzyme involved in fatty acid metabolism and a promising drug target. We previously reported first-generation sEH proteolysis-targeting chimeras (PROTACs) with limited degradation potency and low aqueous and metabolic stability. Herein, we report the development of next-generation sEH PROTAC molecules with improved stability and degradation potency. One of the most potent molecules (compound 8 ) exhibits a half-maximal degradation concentration in the sub-nM range, is stable in vivo , and effectively degrades sEH in mouse livers and brown adipose tissues. Given the role played by sEH in many metabolic and nonmetabolic diseases, the presented molecules provide useful chemical probes for the study of sEH biology. They also hold potential for therapeutic development against a range of disease conditions, including diabetes, inflammation, and metabolic disorders., Competing Interests: The authors declare the following competing financial interest(s): C.M. and B.D.H. are inventors on patents related to the use of sEH inhibitors owned by the University of California. S.K., K.N., C.M., and B.D.H. hold a patent application for the compounds described in this paper (Provisional Application No. 63/642,039)., (© 2024 American Chemical Society.)

Ternary metal carbide TiAlC has been proposed as a metal gate material in logic semiconductor devices. It is a hard-to-etch material due to the low volatility of the etch byproducts. Here, a simple, highly controllable, and dry etching method for TiAlC has been first presented using nonhalogen N 2 /H 2 plasmas at low pressure (several Pa) and 20 °C. A capacitively coupled plasma etcher was used to generate N 2 /H 2 plasmas containing active species, such as N, NH, and H to modify the metal carbide surface. The etch rate of TiAlC was obtained at 3 nm/min by using the N 2 /H 2 plasma, whereas no etching occurred with pure N 2 plasma or pure H 2 plasma under the same conditions. The surface roughness of the TiAlC film etched by N 2 /H 2 plasma was controlled at the atomic level. A smooth etched surface was achieved with a root-mean-square roughness of 0.40 nm, comparable to the initial roughness of 0.44 nm. The plasma properties of the N 2 /H 2 plasmas were diagnosed by using a high-resolution optical emission spectrometer, detecting the NH molecular line at 336 nm. The etching behavior and plasma-surface reaction between N 2 /H 2 plasma and TiAlC were investigated by using in situ spectroscopic ellipsometry, in situ attenuated total reflectance-Fourier transform infrared spectrometry, and X-ray photoelectron spectroscopy. The findings indicate that the N-H, C-N, and Ti(Al)-N bonds form on the TiAlC surface etched by the N 2 /H 2 plasmas. The mechanism for etching of TiAlC involving transformation reactions between inorganic materials (metal carbides) and inorganic etchants (N 2 /H 2 plasma) to form volatile organic compounds such as methylated, methyl-aminated, and aminated metals is proposed. Nonhalogen or nonorganic compound etchants were used during the etching process. The study provides useful insights into microfabrication for large-scale integrated circuits.

Competing Interests: Declaration of interests We declare no competing interests.

Purpose: To determine the physiological status of the retina of eyes with endophthalmitis by examining the electroretinograms (ERGs) recorded with a portable recording system and to determine whether the pretreatment ERG findings were correlated with the best-corrected visual acuity (BCVA) after the treatment., Methods: We examined the medical records of 118 eyes of 108 patients who were diagnosed and treated for infectious endophthalmitis at Saitama Medical University Hospital, Japan, between January 2015 to November 2022. Of these, we studied the 25 eyes of 21 patients who had been evaluated by electroretinography. In bilateral cases, one eye was analyzed. The eyes were classified into those with postoperative endophthalmitis (group S, n = 12) and those with endogenous endophthalmitis (group E, n = 9). Photopic and flicker ERGs were recorded with the RETeval system. The pretreatment clinical factors studied were the ERG components that might be correlated with the post-treatment BCVA., Results: Eyes in Group E with larger amplitude flicker ERGs (P = 0.0053, ρ = -0.8333) had better BCVA after treatment. In Group S, eyes with larger amplitude flicker ERGs (P = 0.0086, ρ = -0.7173), photopic a-waves (P = 0.0323, ρ = 0.6177), and photopic b-waves (P = 0.0055, ρ = -0.7443) had better BCVA after treatment., Conclusions: Simple and rapid ERG evaluations under light-adapted condition are helpful in evaluating the pretreatment retinal function and to determine the visual prognosis in eyes with endophthalmitis., Translational Relevance: Simple and non-time-consuming ERG evaluations are helpful in evaluating the retinal function in eyes with endophthalmitis and predicting the visual prognosis.

Purpose: To determine the physiological status of the retina by electroretinography (ERG) using skin electrodes and the RETeval TM system in eyes that had undergone pars plana vitrectomy (PPV) with silicone oil (SO) tamponade. The vitrectomy was performed for a retinal detachment and proliferative diabetic retinopathy (PDR)., Design: Retrospective case series., Methods: ERGs were recorded with the RETeval TM system (LKC Technologies Inc. Gaithersburg, MD; Welch Allyn, Inc. Skaneateles Falls, NY) from eight eyes with PDR before and after the SO removal. The amplitudes and implicit times of the a- and b-waves of the ERGs before the SO removal were compared to that after the SO removal., Results: ERGs were recordable in four eyes before and after the SO removal and the a- and b-amplitudes improved in three eyes and worsened in one eye after the SO removal. In the remaining four eyes, ERGs were non-recordable both before and after the SO removal., Conclusion: These results indicate that ERGs picked up by skin electrodes can be used to assess the physiology of the retina in eyes with a SO tamponade. The flat ERGs in the SO-filled eye indicated the presence of diffuse retinal damage which was confirmed by the flat ERGs after the SO removal., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Kanai et al.)

We report our findings in a 5-year-old Japanese girl with unilateral optic neuritis who was seropositive for anti-myelin-oligodendrocyte glycoprotein (MOG) antibody. Functional and microstructural changes were assessed longitudinally for 3.5 years by serial recordings of the pattern visual evoked potentials (pVEPs) and optical coherence tomography (OCT) during the acute and chronic phases. On the initial visit, the best-corrected visual acuity (BCVA) in the right eye was light perception. She was treated with 450 mg of intravenous methylprednisolone pulses followed by a gradual tapering of the oral prednisolone. The visual acuity decreased to no light perception, and plasmapheresis combined with high-dose intravenous immunoglobulin therapy was performed. The BCVA quickly improved to 1.0, and no recurrence was detected for approximately four years. The implicit times of N75, P100, and N145 of the pVEPs and peripapillary retinal nerve fiber (pRNFL) thickness in the OCT images were measured during the course of the disease process. The pRNFL thickness of the right eye decreased and was less than one-half of the baseline value at one year and then stabilized. In contrast, the optic pathway function assessed by pVEPs improved. The implicit times of the N75 and P100 components of the right eye were shortened and stabilized at approximately one year. However, the implicit times in the right eye were still longer than that of the left eye. Our findings documented the course of the function and structures of an eye with anti-MOG antibody-positive optic neuritis. This information should be helpful for the understanding of the pathology and prognosis of this disease entity. Further analysis of the pVEPs and structural changes in more cases is needed., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. 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, Tachibana et al.)

Background: Understanding the different patterns of adherence to istradefylline treatment is essential to identifying Parkinson's disease (PD) patients who might benefit from targeted interventions., Objectives: This descriptive study aimed to identify longitudinal istradefylline adherence patterns and to characterize factors associated with them., Methods: We identified PD patients aged 21-99 years who initiated istradefylline treatment in a Japanese hospital administrative database. Group-based trajectory modeling was used to model the monthly proportion of days covered over time to identify distinct 360-day adherence patterns. Factors associated with each adherence pattern were assessed using univariable multinomial logistic regression models., Results: Of 2088 eligible PD patients, 4 distinct adherence groups were identified: consistently high adherence (56.8%); rapidly declining adherence (25.8%); gradually declining adherence (8.5%); and gradually declining and then recovering adherence (9.0%). Compared to the consistently high adherence group, the other groups had the following characteristics associated with a likelihood of lower adherence: the rapidly declining adherence group received fewer dopamine agonists (63.8% vs. 69.4%), monoamine oxidase B (MAO-B) inhibitors (26.8% vs. 31.6%), and catechol-O-methyl transferase inhibitors (31.6% vs. 37.0%) and had a higher prevalence of anxiety/mood disorders (29.9% vs. 24.6%); the gradually declining adherence group received fewer MAO-B inhibitors (22.5% vs. 31.6%) and amantadine (8.4% vs. 16.1%) and had a higher prevalence of mild cognitive impairment/dementia (27.0% vs. 18.8%); and the declining and then recovering adherence group had a higher prevalence of anxiety/mood disorders (34.2% vs. 24.6%)., Conclusions: Clinicians should be aware of the heterogeneous patterns of adherence to istradefylline., Competing Interests: Declaration of competing interest T.F. has been employed by the Department of Digital Health and Epidemiology with support from Eisai Co., Ltd. and Kyowa Kirin Co., Ltd.; and has received consulting fees from Real World Data Co., Ltd. and honoraria from EPS Corporation and Research Institute of Healthcare Data Science (RIHDS). E.N. has received consulting fees from Kyowa Kirin Co., Ltd., and honoraria from AbbVie GK, Daiichi Sankyo Co., Ltd., EA Pharma Co., Ltd., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Ono Pharmaceutical Co., Ltd., Sumitomo Pharma Co., Ltd., and Takeda Pharmaceutical Co., Ltd. H.S., K.S., S.I., and S.A. have been employed by Kyowa Kirin Co., Ltd. S.Y. has no conflicts of interest. S.T.-M. has been employed by the Department of Digital Health and Epidemiology with support from Eisai Co., Ltd. and Kyowa Kirin Co., Ltd.; and has received consulting fees from Real World Data Co., Ltd. and honoraria from RIHDS. K.M. has been employed by the Department of Digital Health and Epidemiology with support from Eisai Co., Ltd. and Kyowa Kirin Co., Ltd. R.T. has received consulting fees from Kyowa Kirin Co., Ltd., and grants from Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Sumitomo Pharma Co., Ltd., honoraria from AbbVie Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Ono Pharmaceutical Co., Ltd., Sumitomo Pharma Co., Ltd., and Takeda Pharmaceutical Co., Ltd., and subcontracting fees (trial cases) from Sanofi K.K., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd. K.K. has received consulting fees from Advanced Medical Care Inc., JMDC Inc., LEBER Inc., and Shin Nippon Biomedical Laboratories Ltd., executive compensation from Cancer Intelligence Care Systems, Inc., honoraria from Chugai Pharmaceutical Co., Ltd., Kaken Pharmaceutical Co., Ltd., and Pharma Business Academy, and grants from Eisai Co., Ltd., Kyowa Kirin Co., Ltd., OMRON Corporation, and Toppan Inc., (Copyright © 2023. Published by Elsevier B.V.)

Background: Elderly living kidney donors (LKDs) are becoming increasingly important in countries with a high prevalence of living-donor kidney transplants and an aging society. This study explored the features of elderly LKDs, focusing on their subsequent outcomes., Methods: This single-center, retrospective, observational study included eligible LKDs who donated their kidneys between April 2008 and July 2022. LKDs were categorized into an elderly (≥70 years at donation) or a non-elderly group (<70 years). We examined pre-operative characteristics and post-operative outcomes, such as kidney function, complications, development of end-stage kidney disease (ESKD), and mortality., Results: Of the 188 LKDs observed for a median of 5.7 years, 31 were in the elderly group (16.5%) and 157 (83.5%) were in the non-elderly group (mean age 72.5 ± 2.7 and 58.2 ± 7.3 years, respectively). No significant differences were observed in hospital stay length or peri-operative complications between groups. Both groups experienced a similar decline in post-donation estimated glomerular filtration rate (eGFR)-approximately 37%. In the elderly group, four LKDs died, and one progressed to ESKD. In the non-elderly group, two LKDs died, and none progressed to ESKD. The cause of death was not strongly suspected to be associated with the donation., Conclusions: eGFR was maintained even in elderly LKDs post-donation. Prioritizing LKDs' safety is paramount; however, donations from elderly people would be acceptable, considering their life expectancy. This can expand the pool of living kidney donors and address the growing demand for kidney transplants., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Neurotoxins have been extensively investigated, particularly in the field of neuroscience. They induce toxic damage, oxidative stress, and inflammation on neurons, triggering neuronal dysfunction and neurodegenerative diseases. Here we demonstrate the neuroprotective effect of a silicon (Si)-based hydrogen-producing agent (Si-based agent) in a juvenile neurotoxic mouse model induced by 6-hydroxydopamine (6-OHDA). The Si-based agent produces hydrogen in bowels and functions as an antioxidant and anti-inflammatory agent. However, the effects of the Si-based agent on neural degeneration in areas other than the lesion and behavioral alterations caused by it are largely unknown. Moreover, the neuroprotective effects of Si-based agent in the context of lactation and use during infancy have not been explored in prior studies. In this study, we show the neuroprotective effect of the Si-based agent on 6-OHDA during lactation period and infancy using the mouse model. The Si-based agent safeguards against the degradation and neuronal cell death of dopaminergic neurons and loss of dopaminergic fibers in the striatum (STR) and ventral tegmental area (VTA) caused by 6-OHDA. Furthermore, the Si-based agent exhibits a neuroprotective effect on the length of axon initial segment (AIS) in the layer 2/3 (L2/3) neurons of the medial prefrontal cortex (mPFC). As a result, the Si-based agent mitigates hyperactive behavior in a juvenile neurotoxic mouse model induced by 6-OHDA. These results suggest that the Si-based agent serves as an effective neuroprotectant and antioxidant against neurotoxic effects in the brain, offering the possibility of the Si-based agent as a neuroprotectant for nervous system diseases., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Due to their high catalytic activity, stability, and economic benefits, Pt-based multi-element alloyed nanoparticles (NPs) are considered promising electrodes for oxygen reduction reactions. However, a synthesis method capable of controlling the reduction reaction of elements with different redox potentials to synthesize multimetallic alloy NPs is yet to be developed. In this study, monodisperse NiPtPd alloy NPs with varying compositions were synthesized using 1-heptanol as a reducing solvent. The selection of low-reducing noble metal precursors and complexing agents is done strategically to adjust the reduction time of metal ions. The spectroscopic results confirmed that olelylamine (OAm) preferentially coordinates with Pt ions, while trioctylphosphine (TOP) preferentially coordinates with Pd ions. Consequently, control of the elemental distribution within the particle is successfully achieved by adjusting the OAm/Pt and TOP/Pd molar ratios. Subsequently, Ni 78 Pt 11 Pd 11 alloy NPs were designed, and their catalytic properties as electrodes in the oxygen reduction reaction (ORR) were examined. Despite a low noble metal content of 22%, the catalytic performance and stability were superior to and comparable to those of commercial Pt NPs, respectively.

Several attempts for speech brain-computer interfacing (BCI) have been made to decode phonemes, sub-words, words, or sentences using invasive measurements, such as the electrocorticogram (ECoG), during auditory speech perception, overt speech, or imagined (covert) speech. Decoding sentences from covert speech is a challenging task. Sixteen epilepsy patients with intracranially implanted electrodes participated in this study, and ECoGs were recorded during overt speech and covert speech of eight Japanese sentences, each consisting of three tokens. In particular, Transformer neural network model was applied to decode text sentences from covert speech, which was trained using ECoGs obtained during overt speech. We first examined the proposed Transformer model using the same task for training and testing, and then evaluated the model's performance when trained with overt task for decoding covert speech. The Transformer model trained on covert speech achieved an average token error rate (TER) of 46.6% for decoding covert speech, whereas the model trained on overt speech achieved a TER of 46.3% ( p > 0.05 ; d = 0.07 ) . Therefore, the challenge of collecting training data for covert speech can be addressed using overt speech. The performance of covert speech can improve by employing several overt speeches., (© 2024. The Author(s).)

Purpose: To determine whether 0.025% povidone-iodine (0.025% PI) in the irrigation solution during vitrectomy for endophthalmitis is safe., Methods: Two cases of bleb-associated endophthalmitis were treated with vitrectomy using 0.025% PI in the irrigation solution. The RETevel electroretinographic (ERG) system with skin electrodes was used to assess the physiology of the retina pre- and postoperatively., Case: Case 1 was a 46-year-old man who had atopic keratoconjunctivitis and underwent trabeculectomy with the creation of a bleb after there was a rise in the intraocular pressure. One month postoperatively, a mild filtering bleb-associated endophthalmitis developed, and the eye was treated with intravitreal and subconjunctival injections of vancomycin (VCM) and ceftazidime (CAZ). After three days, the fundus was not visible and B-mode echography showed an area of high brightness in the retina. Vitrectomy with irrigation with VCM and CAZ, and 0.025% PI was performed successfully. Pre- and postoperative ERGs showed an improvement in both the a- and b-wave amplitudes and the b/a ratio was stable at 2.0. Case 2 was a 63-year-old man who had undergone trabeculectomy for glaucoma. Five years later, the eye developed blebitis which was treated with topical and subconjunctival injections of VCM and CAZ. Three days later, vitreous opacities appeared and a high brightness area was seen in the B-mode echographic images. Vitrectomy with VCM and CAZ, and 0.025% PI irrigation was successfully performed. Comparisons of the pre- and postoperative ERGs found that the a- and b- wave amplitudes of the ERGs increased and the b/a ratio was stable at approximately 1.5., Conclusion: Vitrectomy with 0.025% PI irrigation is safe and ERG recordings with skin electrodes can be used to evaluate the pre- and postoperative retinal physiology safely., Competing Interests: The authors have no conflicts of interest to declare in this work., (© 2024 Sakata et al.)

Background: This study evaluated the safety and effectiveness of combining intravitreal brolucizumab injection with sub-tenon's capsule triamcinolone acetonide injection (STTA) during the loading phase for polypoidal choroidal vasculopathy (PCV)., Methods: In this retrospective observational study, untreated patients with PCV receiving intravitreal brolucizumab injections with STTA during loading at Saitama Medical University Hospital's Eye Center from May 2021 to June 2022 were analyzed. Complete regression rates of polypoidal lesions were assessed using indocyanine green angiography 12 weeks post-treatment initiation., Results: Nineteen patients (19 eyes) participated. Best-corrected visual acuity significantly improved at eight weeks compared to baseline. No significant intraocular pressure increases occurred throughout the loading phase, while central foveal and choroidal thickness significantly reduced at 4, 8, and 12 weeks. Subretinal fluid was present in all patients before treatment, rapidly resolving post-intravitreal brolucizumab injections and STTA, with residual rates of 36.8% (seven eyes) and 5.3% (one eye) at four and 12 weeks, respectively. Intraocular inflammation did not occur during the loading phase, and the complete regression rate of polypoidal lesions was 89.5% (17 eyes)., Conclusions: Combining intravitreal brolucizumab injection with STTA during the loading phase may be one treatment option for PCV management., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Yoshikawa et al.)

The liver acts as a master regulator of metabolic homeostasis in part by performing gluconeogenesis. This process is dysregulated in type 2 diabetes, leading to elevated hepatic glucose output. The parenchymal cells of the liver (hepatocytes) are heterogeneous, existing on an axis between the portal triad and the central vein, and perform distinct functions depending on location in the lobule. Here, using single cell analysis of hepatocytes across the liver lobule, we demonstrate that gluconeogenic gene expression ( Pck1 and G6pc ) is relatively low in the fed state and gradually increases first in the periportal hepatocytes during the initial fasting period. As the time of fasting progresses, pericentral hepatocyte gluconeogenic gene expression increases, and following entry into the starvation state, the pericentral hepatocytes show similar gluconeogenic gene expression to the periportal hepatocytes. Similarly, pyruvate-dependent gluconeogenic activity is approximately 10-fold higher in the periportal hepatocytes during the initial fasting state but only 1.5-fold higher in the starvation state. In parallel, starvation suppresses canonical beta-catenin signaling and modulates expression of pericentral and periportal glutamine synthetase and glutaminase, resulting in an enhanced pericentral glutamine-dependent gluconeogenesis. These findings demonstrate that hepatocyte gluconeogenic gene expression and gluconeogenic activity are highly spatially and temporally plastic across the liver lobule, underscoring the critical importance of using well-defined feeding and fasting conditions to define the basis of hepatic insulin resistance and glucose production.

Background: Acute radiation syndrome (ARS) manifests after exposure to high doses of radiation in the instances of radiologic accidents or incidents. Facilitating regeneration of the bone marrow (BM), namely the hematopoietic stem and progenitor cells (HSPCs), is key in mitigating ARS and multi-organ failure. JNJ-26366821, a PEGylated thrombopoietin mimetic (TPOm) peptide, has been shown as an effective medical countermeasure (MCM) to treat hematopoietic-ARS (H-ARS) in mice. However, the activity of TPOm on regulating BM vascular and stromal niches to support HSPC regeneration has yet to be elucidated., Methods: C57BL/6J mice (9-14 weeks old) received sublethal or lethal total body irradiation (TBI), a model for H-ARS, by 137 Cs or X-rays. At 24 h post-irradiation, mice were subcutaneously injected with a single dose of TPOm (0.3 mg/kg or 1.0 mg/kg) or PBS (vehicle). At homeostasis and on days 4, 7, 10, 14, 18, and 21 post-TBI with and without TPOm treatment, BM was harvested for histology, BM flow cytometry of HSPCs, endothelial (EC) and mesenchymal stromal cells (MSC), and whole-mount confocal microscopy. For survival, irradiated mice were monitored and weighed for 30 days. Lastly, BM triple negative cells (TNC; CD45 - , TER-119 - , CD31 - ) were sorted for single-cell RNA-sequencing to examine transcriptomics after TBI with or without TPOm treatment., Results: At homeostasis, TPOm expanded the number of circulating platelets and HSPCs, ECs, and MSCs in the BM. Following sublethal TBI, TPOm improved BM architecture and promoted recovery of HSPCs, ECs, and MSCs. Furthermore, TPOm elevated VEGF-C levels in normal and irradiated mice. Following lethal irradiation, mice improved body weight recovery and 30-day survival when treated with TPOm after 137 Cs and X-ray exposure. Additionally, TPOm reduced vascular dilation and permeability. Finally, single-cell RNA-seq analysis indicated that TPOm increased the expression of collagens in MSCs to enhance their interaction with other progenitors in BM and upregulated the regeneration pathway in MSCs., Conclusions: TPOm interacts with BM vascular and stromal niches to locally support hematopoietic reconstitution and systemically improve survival in mice after TBI. Therefore, this work warrants the development of TPOm as a potent radiation MCM for the treatment of ARS., (© 2024. The Author(s).)

Aging, chronic high-fat diet feeding, or housing at thermoneutrality induces brown adipose tissue (BAT) involution, a process characterized by reduction of BAT mass and function with increased lipid droplet size. Single nuclei RNA sequencing of aged mice identifies a specific brown adipocyte population of Ucp1-low cells that are pyroptotic and display a reduction in the longevity gene syntaxin 4 (Stx4a). Similar to aged brown adipocytes, Ucp1-STX4KO mice display loss of brown adipose tissue mass and thermogenic dysfunction concomitant with increased pyroptosis. Restoration of STX4 expression or suppression of pyroptosis activation protects against the decline in both mass and thermogenic activity in the aged and Ucp1-STX4KO mice. Mechanistically, STX4 deficiency reduces oxidative phosphorylation, glucose uptake, and glycolysis leading to reduced ATP levels, a known triggering signal for pyroptosis. Together, these data demonstrate an understanding of rapid brown adipocyte involution and that physiologic aging and thermogenic dysfunction result from pyroptotic signaling activation., (© 2024. The Author(s).)

Introduction: Tokyo Guidelines 2018 (TG18) recommend early laparoscopic cholecystectomy (LC) for low-risk acute cholecystitis (AC); however, some patients undergo delayed LC (DLC) after conservative treatment. DLC, influenced by chronic inflammation, is a difficult procedure. Previous studies on LC difficulty lacked objective measures. Recently, TG18 introduced a novel 25 findings difficulty score, which objectively assesses intraoperative factors. The purpose of this study was to use the difficulty score proposed in TG18 to identify and investigate the predictors of preoperative high-difficulty cases of DLC for AC., Methods: We retrospectively reviewed 100 patients with DLC after conservative AC treatment. The surgical difficulty of DLC was evaluated using a difficulty score. Based on previous studies, the highest scores in each category were categorized as grades A-C., Results: The severity of AC was mild in 51 patients and moderate in 49. Surgical outcomes revealed a distribution of difficulty scores, with grade C indicating high difficulty, showing significant differences in operative time, blood loss, achieving a critical view of safety, bailout procedures, and postoperative hospital stay compared with grades A and B. Regarding the preoperative risk factors, multivariate analysis identified age >61 years (p = .008), body mass index >27.0 kg/m 2 (p = .007), and gallbladder wall thickness >6.2 mm (p = .001) as independent risk factors for grade C in DLC., Conclusion: The difficulty score proposed in TG18 provides an objective framework for evaluating surgical difficulty, allowing for more accurate risk assessments and improved preoperative planning in DLC for AC., (© 2024 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Previous studies have primarily focused on quality of imaging in radiotherapy planning computed tomography (RTCT), with few investigations on imaging doses. To our knowledge, this is the first study aimed to investigate the imaging dose in RTCT to determine baseline data for establishing national diagnostic reference levels (DRLs) in Japanese institutions. A survey questionnaire was sent to domestic RT institutions between 10 October and 16 December 2021. The questionnaire items were volume computed tomography dose index (CTDIvol), dose-length product (DLP), and acquisition parameters, including use of auto exposure image control (AEC) or image-improving reconstruction option (IIRO) for brain stereotactic irradiation (brain STI), head and neck (HN) intensity-modulated radiotherapy (IMRT), lung stereotactic body radiotherapy (lung SBRT), breast-conserving radiotherapy (breast RT), and prostate IMRT protocols. Details on the use of motion-management techniques for lung SBRT were collected. Consequently, we collected 328 responses. The 75th percentiles of CTDIvol were 92, 33, 86, 23, and 32 mGy and those of DLP were 2805, 1301, 2416, 930, and 1158 mGy·cm for brain STI, HN IMRT, lung SBRT, breast RT, and prostate IMRT, respectively. CTDIvol and DLP values in institutions that used AEC or IIRO were lower than those without use for almost all sites. The 75th percentiles of DLP in each treatment technique for lung SBRT were 2541, 2034, 2336, and 2730 mGy·cm for free breathing, breath holding, gating technique, and real-time tumor tracking technique, respectively. Our data will help in establishing DRLs for RTCT protocols, thus reducing imaging doses in Japan., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Introduction: Gastrointestinal complications are common after solid organ transplantation. New-onset inflammatory bowel disease (IBD) after transplantation (de novo) is a major differential diagnosis of diarrhea after liver transplantation (LT) because of its high incidence in the field. However, the incidence of IBD after kidney transplantation (KT) remains unknown., Methods: This case series comprised six de novo IBD patients who had undergone KT at our hospital from April 1998 to December 2020. In this period, 232 KT recipients were identified. Participants were analyzed based on their colonoscopy diagnoses. Detailed clinical information regarding both KT- and IBD-related symptoms or outcomes was obtained, and we calculated the incidence of de novo IBD from the date of KT., Results: Of the 232 recipients in the median observation period of 6.1 (interquartile range: 2.6, 10.8) years, six recipients (one with Crohn's disease and five with ulcerative colitis) were diagnosed with de novo IBD. The incidence of de novo IBD after KT was 355.8/100,000 person-years (95% confidence interval, 159.8-791.9 per 100,000 person-years). Bloody stools and diarrhea did not always occur, with bloody stools occurring in three and diarrhea in 2 patients at the time of diagnosis. No recipient developed graft failure or extraintestinal complications (e.g., IBD-related nephritis or arthritis)., Conclusion: Despite a small sample size, this study's results indicate that the incidence of de novo IBD after KT may be similar to that after LT and higher than that in the general population. Larger studies are required to validate these preliminary findings., Competing Interests: H.Y. received lecture fees from Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma, Kowa Co. Ltd., AstraZeneka K.K., Kyorin Pharmaceutical Co. Ltd., and Takeda Pharmaceutical Co. Ltd. outside the submitted work. Fees for consultation for H.Y. were paid to Kyoto University by Magmitt Pharmaceutical Co. and Takeda Pharmaceutical Co. Ltd. outside the submitted work. The other authors declare no conflicts of interest., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Product secretion from an engineered cell can be advantageous for microbial cell factories. Extensive work on nucleotide manufacturing, one of the most successful microbial fermentation processes, has enabled Corynebacterium stationis to transport nucleotides outside the cell by random mutagenesis; however, the underlying mechanism has not been elucidated, hindering its applications in transporter engineering. Herein, we report the nucleotide-exporting major facilitator superfamily (MFS) transporter from the C. stationis genome and its hyperactive mutation at the G64 residue. Structural estimation and molecular dynamics simulations suggested that the activity of this transporter improved via two mechanisms: (1) enhancing interactions between transmembrane helices through the conserved "RxxQG" motif along with substrate binding and (2) trapping substrate-interacting residue for easier release from the cavity. Our results provide novel insights into how MFS transporters change their conformation from inward- to outward-facing states upon substrate binding to facilitate efflux and can contribute to the development of rational design approaches for efflux improvements in microbial cell factories. KEYPOINTS: • An MFS transporter from C. stationis genome and its mutation at residue G64 were assessed • It enhanced the transporter activity by strengthening transmembrane helix interactions and trapped substrate-interacting residues • Our results contribute to rational design approach development for efflux improvement., (© 2024. The Author(s).)

Objectives: The aim of the article is to investigate the associations of disease duration and anti-cyclic citrullinated peptide antibody (ACPA) status with the effectiveness of abatacept in biologic-naïve patients with rheumatoid arthritis (RA)., Methods: We performed post hoc analyses of the Orencia® Registry in Geographically Assembled Multicenter Investigation (ORIGAMI) study of biologic-naïve RA patients aged ≥20 years with moderate disease activity who were prescribed abatacept. Changes in the Simplified Disease Activity Index (SDAI) and Japanese Health Assessment Questionnaire (J-HAQ) at 4, 24, and 52 weeks of treatment were analysed in patients divided according to ACPA serostatus (positive/negative), disease duration (<1/≥1 year), or both., Results: SDAI scores decreased from baseline in all groups. SDAI scores tended to decrease more in the ACPA-positive group and disease duration <1-year group than in the ACPA-negative group and disease duration ≥1-year group, respectively. In the disease duration <1-year group, SDAI tended to decrease more in the ACPA-positive group than in the ACPA-negative group. Disease duration was independently associated with the change in SDAI and SDAI remission at Week 52 in multivariable regression models., Conclusions: These results suggest that starting abatacept within 1 year of diagnosis was associated with greater effectiveness of abatacept in biologic-naïve patients with RA and moderate disease activity., (© Japan College of Rheumatology 2023. Published by Oxford University Press.)

Unsymmetrical disulfides, in which different organic groups are bonded to disulfide bonds, have been synthesized by cross-coupling reactions using thiols as substrates. However, due to the low-binding energy of unsymmetrical disulfides, its disproportionation occurs based on the side reactions with nucleophilic thiols, resulting in the impurity of symmetric disulfides. In this study, we developed a solvent-free synthesis method for unsymmetrical disulfides using thiosulfonates, thiols, and a base. This synthetic method enabled us to obtain highly pure diaryl-substituted unsymmetrical disulfides with particularly low-binding energy without control over the nucleophilicity and elimination properties of the substrate. Furthermore, it was observed that the disproportionation of unsymmetrical disulfides occurred in the solvent. This means that solvent-free condition is one of the factors to obtain unsymmetrical disulfides. As a new application of unsymmetrical disulfides, we applied unsymmetrical disulfides to cathode active materials of lithium batteries based on the reversible multi-electron redox activity of S-S bonds. The batteries using unsymmetrical disulfide cathode-active materials with a carbon nanotube exhibited initial capacities of 127 and 158 Ah/kg, equal to 42 and 53% of their theoretical ones. We demonstrated that unsymmetrical disulfides could be used as cathode-active materials for rechargeable batteries.

A 53-year-old man was presented with refractory panniculitis on the left upper arm that had persisted for 10 months. The patient was diagnosed with lupus profundus, wherein oral glucocorticoid therapy was initiated. Four months prior, ulceration was observed in the same area. Dapson was administered instead, scarring the ulcer but enlarging the panniculitis. Five weeks earlier, he developed a fever, productive cough, and dyspnoea. Three weeks earlier, a skin rash was observed on the forehead, left auricle posterior to the neck, and extensor aspect of the left elbow. Chest computed tomography showed pneumonia in the right lung, after which the patient's dyspnoea worsened. The patient was admitted and diagnosed with anti-MDA5 antibody-positive amyopathic dermatomyositis (ADM) based on skin findings, hyperferritinaemia, and rapidly progressive diffuse lung shadows. Glucocorticoid pulse therapy, intravenous cyclophosphamide, and tacrolimus were initiated, and later, plasma exchange therapy was combined. However, his condition worsened and required management with extracorporeal membrane oxygenation. The patient expired on day 28 after hospitalisation. An autopsy revealed hyalinising to fibrotic stages of diffuse alveolar damage. Strong expression of myxovirus resistance protein A was observed in three skin biopsy specimens from the time of initial onset, consistent with ADM. Anti-MDA5 antibody-positive ADM not only manifests typical cutaneous symptoms, but also rarely occurs with localised panniculitis, such as in the present case. In patients with panniculitis of unknown aetiology, the possibility of initial symptoms of ADM should be included in the differential diagnosis., (© Japan College of Rheumatology 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Patients with systemic lupus erythematosus (SLE) occasionally develop thrombotic thrombocytopenic purpura (TTP), which can be fatal. Here, we report a case of TTP developing 3 years after SLE remitted with rituximab (RTX) therapy. A 50-year-old woman was treated with RTX for marked immune thrombocytopenic purpura and autoimmune haemolytic anaemia due to SLE relapse. After induction of remission, she was treated with prednisolone alone without maintenance therapy with RTX. Approximately 3 years later, she was readmitted with marked thrombocytopenia and severe renal dysfunction. On admission, she was diagnosed with TTP for the first time based on severe reduction in a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) activity and detection of ADAMTS13 inhibitors. CD19+ B cells in the patient's serum increased to 34%, suggesting that B cells had reactivated once the effect of RTX had subsided. The patient was successfully treated with plasmapheresis, glucocorticoid pulse therapy, and RTX. There are no previous reports of newly diagnosed TTP with ADAMTS13 inhibitor production after having achieved remission of SLE with RTX. Therefore, our report also discusses the potential mechanisms of production of new autoantibodies after B-cell depletion therapy., (© Japan College of Rheumatology 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Small cell neuroendocrine carcinoma is rare among urinary bladder cancer types, and to date, there are no case reports of concurrent antitranscriptional intermediary factor 1- γ antibody-positive dermatomyositis. We describe the case of a 69-year-old Japanese man who presented with elevated creatine kinase levels and haematuria on medical examination. Approximately one month later, he developed dysphagia. Laryngoscopy confirmed laryngeal dysfunction. He also presented with muscle weakness and a skin rash. Magnetic resonance imaging of the upper extremities suggested bilateral brachial muscle myositis. He was diagnosed as having dermatomyositis and was later found to be positive for antitranscriptional intermediary factor 1- γ antibody. Computed tomography revealed an intravesical space-occupying lesion and right iliac lymphadenopathy, suggesting urinary bladder cancer. The patient was admitted to our hospital for treatment. Urinary bladder biopsy confirmed small cell neuroendocrine carcinoma because tumour cells were positive for synaptophysin, CD56, and chromogranin A. Thus, the patient was diagnosed as having an antitranscriptional intermediary factor 1- γ antibody-positive dermatomyositis concomitant with urinary bladder small cell neuroendocrine carcinoma. The patient was treated with glucocorticoid and intravenous immune globulin therapy for dermatomyositis. Radiotherapy was selected for the carcinoma. Although muscle weakness and skin symptoms improved with treatment, dysphagia persisted. Furthermore, expression of the transcriptional intermediary factor 1- γ protein in tumour cells was also confirmed by immunohistochemistry, but the significance is unknown. It should be noted that antitranscriptional intermediary factor 1- γ antibody-positive dermatomyositis can occur concomitantly with such a rare malignancy., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Hiroyuki Hounoki et al.)

Aim: The aim of the present study was to clarify the relationship between the Banff score of the 7-year protocol biopsy and the allograft outcome., Methods: One-hundred-and-eighty-four patients received kidney transplantation from 2002 to 2008. We excluded patients aged <20 years at transplantation ( n  = 24), those who did not undergo a 7-year protocol biopsy ( n  = 66), and those who underwent for-cause biopsy ( n  = 5). Consequently, 89 patients who underwent a 7-year protocol biopsy were enrolled. We analyzed the relationship between the clinicopathological findings 7 years after transplantation and the estimated glomerular filtration rate (eGFR) change per year and allograft survival. Histological evaluation was performed using the Banff 2015 classification., Results: Among the clinicopathological findings, each Banff mesangial matrix increase (mm) score ≥1 and proteinuria ≥1+ was independently associated with the eGFR decline per year during a median follow-up of 73 months. Furthermore, in the model of the clinicopathological findings including the presence of mm with proteinuria, mm ≥1 alone and mm ≥1 with proteinuria were each independently associated with the eGFR decline. The graft survival was significantly worse for those with mm ≥1 with proteinuria than those with mm ≥1 without proteinuria., Conclusion: Among the 7-year protocol biopsy findings, the presence of mm alone and mm with proteinuria were each significant predictors of eGFR decline. The presence of both proteinuria and mm had a negative impact on graft survival. These results underscore the significance of the Banff mm score and proteinuria at the time of the 7-year protocol biopsy to predict the allograft outcome.

Objectives: The variable region of most ACPA IgG molecules in the serum of RA patients carries N-glycan (N-glycanV). To analyse the pathogenicity of N-glycanV of ACPAs, we analysed the pathogenicity of a monoclonal ACPA, CCP-Ab1, with or without N-glycanV, which had been isolated from a patient with RA., Methods: CCP-Ab1 with no N-glycosylation site in the variable region (CCP-Ab1 N-rev) was generated, and antigen binding, the effect on in vitro differentiation of osteoclasts from bone marrow mononuclear cells of autoimmune arthritis-prone SKG mice (the cell size of TRAP+ cells and bone resorption capacity) and the in vivo effect on the onset or exacerbation of autoimmune arthritis in SKG mice were evaluated in comparison with glycosylated CCP-Ab1., Results: Amino acid residues in citrullinated peptide (cfc1), which are essential for binding to CCP-Ab1 N-rev and original CCP-Ab1, were almost identical. The size of TRAP+ cells was significantly larger and osteoclast bone resorption capacity was enhanced in the presence of CCP-Ab1, but not with CCP-Ab1 N-rev. This enhancing activity required the sialic acid of the N-glycan and Fc region of CCP-Ab1. CCP-Ab1, but not CCP-Ab1 N-rev, induced the exacerbation of experimental arthritis in the SKG mouse model., Conclusions: These data showed that N-glycanV was required for promoting osteoclast differentiation and bone resorption activity in both in vitro and in vivo assays. The present study demonstrated the important role of N-glycanV in the exacerbation of experimental arthritis by ACPAs., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Lacrimal drainage pathway disease-associated keratopathy (LDAK) has been associated with corneal perforation, which arises from both infectious and non-infectious corneal disorders. However, patients with corneal perforation are often not routinely tested for LDAK, and the potential risk posed by LDAK in the development of corneal ulcers has not been investigated in detail. This study aimed to assess the proportion and characteristics of LDAK in patients with non-infectious corneal perforation using lacrimal syringing test. This study enrolled 56 patients with corneal perforation treated at Saitama Medical University Hospital between January 2016 and September 2022. The causes of corneal perforation were trauma (n = 17, 30%), infection (n = 19, 34%), non-infection (n = 16, 29%), and unknown (n = 4, 7%). A lacrimal syringing test was performed on 12 patients with non-infectious corneal perforation and 4 with an unknown diagnosis. Among the 16 patients with non-infectious corneal perforation, 13 (81%) had lacrimal drainage disease, but only 3 (19%) patients had lacrimal puncta, as revealed by slit-lamp examinations. The primary bacterial species identified in lacrimal obstructive disease and lacrimal canaliculitis were Staphylococcus spp. and Actinomycetes spp. respectively. Lower temporal and peripheral corneal perforations were common. All patients underwent lacrimal surgery, and 6 (38%) were treated for corneal perforation without corneal surgery. Interestingly, several patients with LDAK who did not exhibit any lacrimal duct obstruction on slit-lamp examination. The study findings demonstrate the significance of the lacrimal syringing test for assessing LDAK in patients with corneal perforation, indicating LDAK as a potential cause of corneal perforation., (© 2023. The Author(s).)

Introduction: It is reported that eyes with a branch retinal artery occlusion (BRAO) had normal full-field electroretinography (ERG) but the response of the multifocal electroretinography (mfERG) was reduced in the area of the arterial occlusion. Optical coherence tomography angiography (OCTA) is a recently appeared modality that can evaluate microvascularizations in different retinal layers and in different regions of the retina. The purpose of this study was to determine the density of the microcirculation and the function of the macular area of eyes with BRAO, and to determine whether they are significantly correlated., Methods: The OCTA and mfERG findings of 7 eyes of 6 patients (3 men, 3 women) were studied. The mean age of the patients was 71.7±10.6 years. The OCTA examinations were made with volume scans of 3 × 3 and 6 × 6 mm squares centered on the fovea. The macular vessel densities (mVD) in the superficial retinal layer (SRL) and deep retinal layer (DRL) were measured for the superior and inferior halves of 3  × 3  and 6  × 6 mm diameter concentric circles. The mfERGs were recorded with targets set to stimulate the focal areas of the retina corresponding to the areas examined by OCTA., Results: The OCTA examinations showed that the mVD of the 3 mm concentric circle in the SRL was significantly lower on the affected side than on the unaffected side (P = 0.022). No such difference was observed in the DRL. The N1 amplitude of the 20.2° concentric circle and the N1-P1 amplitude of the 10.1° concentric circle of the mfERGs were significantly smaller on the affected side than on the unaffected side (P = 0.047 and 0.031). A significant positive correlation was found between the mVD of the 6 mm concentric circle in the DRL and the P1-N2 amplitude of the 20.2° concentric circle ( ρ = -0.929 and p = 0.003)., Discussion: These findings indicate that OCTA images may be able to show changes in the density of the retinal macular microcirculation, and the mfERGs may be able to show alterations in the function of the macular area of the eyes with BRAO. A layer-by-layer analysis of the local retinal microcirculation and function should help in determining the pathogenesis of BRAO., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Igawa, Amaki, Kanno, Tachibana, Konno, Yoshikawa, Matsumoto, Shoji, Makita and Shinoda.)

Introduction: Dellen is a corneal disease characterized by shallow, saucer-like excavations at the corneal margin. Herein, we presented a case of dellen formation that developed following a 27-gauge pars plana vitrectomy (PPV) and was rapidly resolved using scleral and conjunctival sutures., Case Presentation: A 73-year-old woman underwent a 27-gauge PPV for the epiretinal membrane of the right eye. Intraoperatively, owing to coexisting diabetic retinopathy, the peripheral vitreous was shaved, and retinal photocoagulation was performed on the peripheral retina. The intraocular pressure (IOP) was 15 mm Hg on 1 day after the PPV and on postoperative day 4; however, on day 14, the IOP decreased to 10 mm Hg, and conjunctival bleb formation was observed. By day 18, the bleb height remained unchanged, and dellen formation was noted at the corneal periphery. Because of marked corneal thinning, conjunctival and scleral sutures were placed 20 days following the PPV. Intraoperative findings revealed leakage from the scleral wound at the trocar puncture site. The IOP increased to 20 mm Hg at 19 h following the suture, resulting in the disappearance of the bleb and dellen. Since then, the bleb or dellen did not recur., Conclusion: We encountered a case of late-onset scleral wound cleavage 2 weeks following microincision vitreous surgery, resulting in bleb and dellen formation, which was immediately managed by the scleral and conjunctiva suturing., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Abstract: Performing endothelial keratoplasty in an eye with a damaged or irregular iris can result in uneven air filling, air escape behind the pupil, anterior iris curvature, a shallow anterior chamber, an uneven anterior chamber depth, difficulty inserting and opening the graft, and iris trauma. We herein present a modified basket suture technique to prevent these iris complications. Before insertion of the corneal donor graft, a double-armed 9-0 polypropylene suture on a curved needle is inserted from 4 equidistant points at the corneal limbus to create a box configuration directly anterior to the iris. These sutures prevent the iris from moving toward the cornea and the anterior chamber from becoming shallow when air replacement is performed. The suture also reduces intraoperative or postoperative iris-related problems because the air filling is more uniform and less prone to migration., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: The purpose of this study is to evaluate the influence of super-resolution deep learning-based reconstruction (SR-DLR), which utilizes k-space data, on the quality of images and the quantitation of the apparent diffusion coefficient (ADC) for diffusion-weighted images (DWI) in brain magnetic resonance imaging (MRI)., Methods: A retrospective analysis was performed on 34 patients who had undergone DWI using a 3 T MRI system with SR-DLR reconstruction based on k-space data in August 2022. DWI was reconstructed with SR-DLR (Matrix = 684 × 684) and without SR-DLR (Matrix = 228 × 228). Measurements were made of the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) in white matter (WM) and grey matter (GM), and the full width at half maximum (FWHM) of the septum pellucidum. Two radiologists assessed image noise, contrast, artifacts, blur, and the overall quality of three image types using a four-point scale. Quantitative and qualitative scores between images with and without SR-DLR were compared using the Wilcoxon signed-rank test., Results: Images with SR-DLR showed significantly higher SNRs and CNRs than those without SR-DLR (p < 0.001). No statistically significant variances were found in the apparent diffusion coefficients (ADCs) in WM and GM between images with and without SR-DLR (ADC in WM, p = 0.945; ADC in GM, p = 0.235). Moreover, the FWHM without SR-DLR was notably lower compared to that with SR-DLR (p < 0.001)., Conclusion: SR-DLR has the potential to augment the quality of DWI in DL MRI scans without significantly impacting ADC quantitation., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)