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Abstract Relativistic Runaway Electrons Avalanches (RREAs) development depends on the applied electric field and the environment's air density. This dependency controls the RREA exponential growth length scale. The RREA development affects the bremsstrahlung excess occurring due to the passage of charged particles through the thundercloud's electric fields, the gamma‐ray glow. We used Monte Carlo simulations to develop an empirical model showing the RREA behavior in a realistic atmospheric density profile. The new formulation shows how the density variation modulates the electron population under electric field strengths near the RREA electric field threshold. The model limits the initial RREA altitude range as a function of the electric field strength. The new model is valid between ∼0.6 and ∼18 km, covering the relevant heights to investigate the generation of ground‐detected gamma‐ray glows.

Abstract Gamma‐ray glows are observational evidence of relativistic electron acceleration due to the electric field in thunderclouds. However, it is yet to be understood whether such relativistic electrons contribute to the initiation of lightning discharges. To tackle this question, we started the citizen science “Thundercloud Project,” where we map radiation measurements of glows from winter thunderclouds along Japan's sea coast area. We developed and deployed 58 compact gamma‐ray monitors at the end of 2021. On 30 December 2021, five monitors simultaneously detected a glow with its radiation distribution horizontally extending for 2 km. The glow terminated coinciding with a lightning flash at 04:08:34 JST, which was recorded by the two radio‐band lightning mapping systems, FALMA and DALMA. The initial discharges during the preliminary breakdown started above the glow, that is, in vicinity of the electron acceleration site. This result provides one example of possible connections between electron acceleration and lightning initiation.

In this study, NiFe2O4 nanoparticles were prepared as a thermophilic agent for magnetic thermotherapy. To improve biocompatibility, the particles were coated with polyethylene glycol, which is hydrophilic and nontoxic; X-ray diffraction measurements confirmed that the particle size could be controlled to 3, 6, 9, and 17 nm. Fourier-transform infrared spectroscopy confirmed PEG modification to the particles. Biocompatibility with cells were improved by coating with PEG of high molecular weight. The heat-generating effect of the particles was investigated by measuring the magnetic susceptibility and temperature rise in an AC magnetic field. Furthermore, a device using a zero-voltage switching circuit was developed to generate heat. Finally, in vitro experiments using human breast cancer cells were successfully performed to confirm the onset of the hyperthermia effect.

In 2015, the Gamma-Ray Observation of Winter Thunderstorms (GROWTH) collaboration launched a mapping observation campaign for high-energy atmospheric phenomena related to thunderstorms and lightning discharges. This campaign has developed a detection network of gamma rays with up to 10 radiation monitors installed in the cities of Kanazawa and Komatsu, Ishikawa Prefecture, Japan, where low-charge-center winter thunderstorms frequently occur. During four winter seasons from October 2016 to April 2020, a total of 70 gamma-ray glows, i.e., minute-lasting bursts of gamma rays originating from thunderclouds, were detected. Their average duration is 58.9 s. Among the detected events, 77% were observed at night. The gamma-ray glows can be classified into temporally symmetric, temporally asymmetric, and lightning-terminated types based on their count-rate histories. An averaged energy spectrum of the gamma-ray glows is well fitted with a power-law function with an exponential cutoff, whose photon index, cutoff energy, and flux are 0.613±0.009 MeV, 4.68±0.04 MeV, and (1.013±0.003)×10^{−5} erg cm^{−2}s^{−1} (0.2–20.0 MeV), respectively. The present paper provides a catalog of gamma-ray glows and their statistical analysis detected during winter thunderstorms in the Kanazawa and Komatsu areas.

The aim of this study was to investigate the feasibility of human hepatoblastoma cell line (Hep G2), which differentiates by spheroid formation, and treatment with sodium butyrate (SB) as a cell source for hybrid artificial liver (HAL). Hep G2 spontaneously formed spheroids in polyurethane foam (PUF) within 3 days of culture and restored weak ammonia removal activity. Treatment with SB, which is a histone deacetylase inhibitor, further increased the ammonia removal activity of Hep G2 spheroids in a concentration-dependent manner. The activation of ornithine transcarbamylase—a urea cycle enzyme—was significantly related to the upregulation of ammonia removal by spheroid formation, but scarcely contributed to the further upregulation following SB treatment. In contrast with ammonia removal, treatment with SB reduced the albumin secretion of Hep G2 spheroids in a concentration-dependent manner. In the PUF-HAL module in a circulation culture, the ammonia removal rate and albumin secretion rate (per unit volume of the module) of Hep G2 spheroids treated with 5 mM SB were almost the same as those of primary porcine hepatocyte spheroids. These results suggest that simultaneous use of spheroid formation and SB treatment in Hep G2 is beneficial in enhancing the functions of human hepatocytes with potential applications in regenerative medicine and drug screening.

We investigated the availability of human hepatoblastoma cell line (Hep G2), compared with human primary hepatocytes (HH) and porcine primary hepatocytes (PH), as a cell source for the hybrid artificial liver support system (HALSS) by using polyurethane foam (PUF). All three kinds of hepatocytes spontaneously formed spherical multicellular aggregates (spheroids) of 100–200 μm diameter in the pores of PUF within 3 days of culture. In a PUF stationary culture, Hep G2 spheroids recovered the ammonia removal activity that was lost in monolayer culture, although the removal for each unit cell number was about one tenth that of HH spheroids and about one eighth of PH spheroids. The synthesis activities of albumin and fibrinogen of each unit cell number of Hep G2 were also upregulated by PUF spheroid culture, and were about twice as high as in monolayer culture. The albumin secretion activity of Hep G2 spheroids was almost the same as that of PH spheroids. HH scarcely secreted these proteins in this experiment, probably because they were cultured in a serum-free medium. In the PUF module in a circulation culture, HH had high ammonia removal and low synthesis activities similar to stationary culture. Hep G2 proliferated to a high cell density, such as about 4.8 × 107 cells/cm3-module at 10 days of culture. Although Hep G2 spheroids had low ammonia removal activity in each cell, the removal rate in the PUF module was almost the same as for PH at 7 days of culture because of the high cell density culture by cell proliferation. The albumin secretion rate by Hep G2 in the PUF module also increased with cell proliferation and was about 10 times higher than the initial rate for PH at 7 days of culture. These results suggest that Hep G2 is a potential cell source for the PUF-HALSS.

The cell morphology and expression of differentiated functions of primary rat hepatocytes on a titanium dioxide (TiO2) gel surface were investigated. Polystyrene culture dishes were coated with TiO2 gel by spin-coating an ethanol solution of titanium n-butoxide, hydrolyzing in a humidity chamber and drying with nitrogen gas. The TiO2 gel layer formed on the polystyrene dishes was transparent and robust, and its surface was quite flat. Rat hepatocytes inoculated on the TiO2 gel-coated polystyrene dishes gradually accumulated with increasing culture time, and then spontaneously formed many hepatocyte spheroids at 90 ± 21 μm diameter from about 3 days of culture. The diameter of the spheroids increased during the culture, and was 151 ± 43 μm at 14 days of culture. Ammonia removal and albumin secretion by hepatocytes on the TiO2 gel-coated polystyrene dishes were maintained at a high level for at least 14 days of culture compared with on a type I collagen-coated dish and a non-coated polystyrene dish. These results indicate that TiO2 gel is an adequate material for hepatocyte spheroid formation and long-term culture of spheroids. [ABSTRACT FROM AUTHOR]

Background: Although in reversible takotsubo cardiomyopathy (TC), wall motion generally recovers dramatically within a few weeks, there are few data on changes in autonomic function in this condition. Aim: To investigate cardiac autonomic function in the acute and chronic phases of TC. Methods: Ten patients with TC (mean age 70.1 ± 13.7 years) underwent cardiac catheterization on the first hospital day, when left ventricular (LV) ejection fraction (EF) was calculated. A Holter electrocardiographic study was performed within 3 days after the onset of symptoms (0 months) and 3 months after discharge (3 months). The standard deviation of the mean cycle length of normal–normal R–R (NN) intervals over 24 h (SDNN), and the 24-h standard deviation of the mean value of the difference between the NN intervals for each 5-min segment (SDANN), were calculated according to time-area analysis of heart rate variability over 24 h. Frequency domain analysis was also done. Results: Coronary angiography in the acute and chronic phases revealed no significant stenosis in any TC patient. LV wall motion returned to normal in 17.6 ± 6.4 days. LVEF was 45.7 ± 8.8% in the acute phase and 69.8 ± 6.8% after the improvement of wall motion (p p = 0.01) and from 79.9 ± 34.7 to 99.3 ± 40.3 ms (p = 0.03), respectively. No significant changes were observed in frequency domain parameters. Discussion: These results support our previous hypothesis that TC might be caused by neurogenic stunning of the myocardium, due to acute autonomic dysfunction. [ABSTRACT FROM AUTHOR]

Competing Interests: The authors declare that they have no conflict of interest.

The relatively low strength of bioabsorbable screws is a critical clinical issue. A shallower thread depth will increase a screw's strength, but the pull-out strength of the screw will decrease proportionally with the thread depth. We sought to provide further clarification of the relationships between (i) the thread depth and the pull-out strength, and (ii) the minor diameter and the shearing and bending strengths in bioabsorbable screws made of uncalcined and unsintered hydroxyapatite particles and poly-L-lactide (u-HA/PLLA). Seven types (thread depth from 0.1-0.7 mm) of screws with a major diameter of 4.5 mm were manufactured. Each screw type's pull-out strength was investigated using simulated bone. A shearing test and three-point bending test were both used to measure the physical strength of the screws. We then analyzed the relationships between the mechanical findings and the thread depth. The relationship between the thread depth and the pull-out strength showed a positive biphasic linear correlation with a boundary at 0.4-mm thread depth. The relationships between the minor diameter and both the shearing and bending strengths showed positive linear correlations within the range of dimensions tested. Within the scope of this study, a 0.4-mm thread depth proved to be an appropriate value that provides sufficient pull-out strength and screw strength for u-HA/PLLA screws with a 4.5-mm major diameter., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: S. Imade, Y. Uchio, Shimane prefecture and Teijin Medical Technologies Co. own the design rights (JPS-1700438, 1700439, 1700440) for the new type of screw investigated in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

While electroencephalography (EEG) and magnetoencephalography (MEG) are well-established noninvasive methods in neuroscience and clinical medicine, they suffer from low spatial resolution. Electrophysiological source imaging (ESI) addresses this by noninvasively exploring the neuronal origins of M/EEG signals. Although subcortical structures are crucial to many brain functions and neuronal diseases, accurately localizing subcortical sources of M/EEG remains particularly challenging, and the feasibility is still a subject of debate. Traditional ESIs, which depend on explicitly defined regularization priors, have struggled to set optimal priors and accurately localize brain sources. To overcome this, we introduced a data-driven, deep learning-based ESI approach without the need for these priors. We proposed a four-layered convolutional neural network (4LCNN) designed to locate both subcortical and cortical sources underlying M/EEG signals. We also employed a sophisticated realistic head conductivity model using the state-of-the-art segmentation method of ten different head tissues from individual MRI data to generate realistic training data. This is the first attempt at deep learning-based ESI targeting subcortical regions. Our method showed excellent accuracy in source localization, particularly in subcortical areas compared to other methods. This was validated through M/EEG simulations, evoked responses, and invasive recordings. The potential for accurate source localization of the 4LCNNs demonstrated in this study suggests future contributions to various research endeavors such as the clinical diagnosis, understanding of the pathophysiology of various neuronal diseases, and basic brain functions., Competing Interests: The authors have no conflicts to disclose., (© 2024 Author(s).)

A simple method that improves the resolution of the phase measurement of differential phase-contrast (DPC) scanning transmission electron microscopy for closed-type environmental cell applications was developed and tested using a model sample simulating environmental cell observations. Because the top and bottom membranes of an environmental cell are typically far apart, the images from these membranes are shifted widely by tilt-series acquisition, and averaging the images after alignment can effectively eliminate undesired signals from the membranes while improving the signal from the object of interest. It was demonstrated that a phase precision of 2π/100 rad is well achievable using the proposed method for the sample in an environmental cell., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Society of Microscopy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Purpose: Non-Hodgkin lymphoma (NHL) sometimes occurs in soft tissue (referred to as soft tissue lymphoma or soft tissue NHL), often mimicking soft tissue tumors. Despite some clinical indicators, accurate diagnosis of soft tissue NHL before biopsy remains challenging. We investigated the diagnostic value of serum soluble interleukin-2 receptor (sIL-2R) levels and magnetic resonance imaging (MRI) as an initial tool to assess the likelihood of soft tissue NHL., Methods: We analyzed 36 cases of pathologically proven soft tissue NHL initially suspected as soft tissue tumors alongside 48 control cases of soft tissue sarcoma or carcinoma. Patient medical charts and MRI scans were retrospectively reviewed and statistically analyzed, focusing on assessing the diagnostic efficacy of soft tissue NHL., Results: The diagnostic accuracy of soft tissue NHL combining the appearance of homogeneity on MRI (T2-weighted and/or short-time inversion recovery [STIR] images) and sIL-2R value (≧ 904 U/mL) yielded a sensitivity of 78 % and 86 %, and specificity of 83 % and 88 %, respectively. Meeting one or both criteria increased the sensitivity to a maximum of 92 %, albeit with a specificity of 71 %. When both criteria were met, sensitivity and specificity were 72 % and 100 %, respectively., Conclusion: The integrated approach of combining MRI and sIL-2R demonstrated excellent efficacy in predicting the diagnosis of soft tissue NHL, which was initially referred to as soft tissue tumor., Competing Interests: None of the investigators has any conflict of interest of any kind whatsoever with the research and its outcome., (© 2024 The Authors. Published by Elsevier B.V. on behalf of Professor P K Surendran Memorial Education Foundation.)

Peripheral nerve stimulation (PNS) and motor point stimulation (MPS) are noninvasive techniques used to induce muscle contraction, aiding motor function restoration in individuals with neurological disorders. Understanding sensory inputs from PNS and MPS is crucial for facilitating neuroplasticity and restoring impaired motor function. Although previous studies suggest that MPS could induce Ia-sensory inputs less than PNS, experimental evidence supporting this claim is insufficient. Here, we implemented a conditioning paradigm combining transcutaneous spinal cord stimulation (tSCS) with PNS or MPS to investigate their Ia-sensory inputs. This paradigm induces postactivation depression of spinal reflexes associated with transient decreases in neurotransmitter release from Ia-afferent terminals, allowing us to examine the Ia-sensory input amount from PNS and MPS based on the depression degree. We hypothesized that MPS would induce less postactivation depression than PNS. Thirteen individuals underwent MPS and PNS on the soleus muscle as conditioning stimuli, with tSCS applied to the skin between the spinous processes (L1-L2) as test stimuli. PNS- and MPS-conditioned spinal reflexes were recorded at five interstimulus intervals (ISIs) and four intensities. Results revealed that all PNS conditioning showed significant decreases in spinal reflex amplitudes, indicating postactivation depression. Furthermore, PNS conditioning exhibited greater depression for shorter ISIs and higher conditioning intensities. In contrast, MPS conditioning demonstrated intensity-dependent depression, but without all-conditioning depression and clear ISI dependency as seen in PNS conditioning. In addition, PNS induced significantly greater depression than MPS across most conditions. Our findings provide experimental evidence supporting the conclusion that MPS activates Ia-sensory nerves less than PNS. NEW & NOTEWORTHY Peripheral nerve stimulation (PNS) and motor point stimulation (MPS) induce neuroplasticity, but differences in their effects on Ia-sensory inputs are unclear. We investigated their Ia-sensory inputs using a conditioning paradigm with spinal reflexes. Results showed that PNS conditioning significantly inhibited spinal reflexes than MPS conditioning, indicating greater postactivation depression due to Ia-sensory nerve activation. These findings provide experimental evidence that MPS activates Ia-sensory nerves to a lesser extent than PNS, enhancing our understanding of neuroplasticity.

Background: Endovascular abdominal aortic repair (EVAR) has a significantly higher revision rate than open repair, primarily due to type 2 endoleak (2EL). Although 2ELs are considered benign, late open conversion (LOC) due to the expansion of the aneurysm diameter of the 2EL is a concern in the mid- and long-term. In this study, we investigated the impact of embolization of the inferior mesenteric artery (IMA) or lumbar artery (LA) at the time of the initial EVAR and its long-term outcomes., Methods: Between April 2008 and December 2021, 743 EVAR procedures for abdominal aortic aneurysms were performed at our institution. The patients were divided into 2 groups at the time of initial surgery, namely, 215 and 528 patients in the embolization (Group E) and nonembolization (Group N) groups, respectively. Branch embolization was performed in patients with an IMA diameter ≥3 mm and LA diameter ≥2 mm on preoperative computed tomography. Re-embolization with EL was performed in patients with a diameter enlargement ≥10 mm, and LOC was performed in patients with continued enlargement ≥15 mm after re-embolization. The mean follow-up period was 7.0 years., Results: The mean number of branch embolizations was 2.3 ± 1.1. Intraoperatively, the operative time, fluoroscopy time, irradiation dose, and contrast medium use were significantly higher in Group E than in Group N. There was a significant difference between the 2 groups regarding shrinkage (Group E versus Group N: 45.6% versus 37.3%; P = 0.03) and enlargement (Group E versus Group N: 9.3% vs. 19.5%; P < 0.001) of the aneurysm diameter by > 5 mm after EVAR. In the mid- and long-term, the avoidance rate of 2EL reintervention was significantly lower in Group E at 5 years (93.5% vs. 88.6%) and 10 years (87.5% vs. 76.4%; P = 0.04). LOC prevention was 5 years; Group E: 100% vs. 96.9% for Group N and 10 years; Group E: 98.8% vs. 92.5% for Group N, significantly lower in Group E (P = 0.02)., Conclusions: The impact of branch embolization at the time of the initial EVAR is believed to prevent enlargement of the aneurysmal sac and LOC. However, prolonged operation time, increased radiation exposure, and the use of contrast medium have been debated. To improve the long-term results of EVAR, embolisms of both the IMA and LA are required., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Fatty infiltration (FI) and muscle atrophy (MA) in the rotator cuff muscles following rotator cuff tears (RCT) persist postrepair, increasing the risk of re-tears. Brown adipocyte-like "beige adipocytes" are expected to have a therapeutic effect on intramuscular FI and MA due to their lipolytic activity and the muscle regenerative effects of their secreted factors. However, whether parathyroid hormone (PTH) ameliorates the already advanced FI and MA remains unknown. Therefore, this study aimed to clarify whether PTH promotes the expression of beige adipocytes and ameliorates advanced FI and MA following chronic RCT in rats., Methods: Supraspinatus muscles were harvested from rats with chronic RCT after 4 or 8 weeks of PTH treatment and compared to those in the control group or to those at the start of treatment. FI was assessed by Oil Red O staining, and the staining area was evaluated as a percentage of the muscle cross-sectional area. MA was evaluated by measuring muscle wet weight and cross-sectional area of muscle fiber. Beige adipocyte expression was evaluated by immunostaining for uncoupling protein 1 (UCP1). Fibro-adipogenic progenitors (FAPs) were separated from muscle-injured mice. We assessed whether PTH could diminish fat droplet accumulation by promoting the differentiation of FAPs into beige adipocytes., Results: After 4 weeks, PTH reduced the area fraction of FI in the rat supraspinatus muscle following chronic RCT compared with that at the beginning of treatment (P = .028). In addition, PTH increased wet muscle mass (P < .001), and muscle fiber cross-sectional area (P = .018) compared with measurements at the start of treatment. PTH administration promoted the expression of UCP1, a beige adipocyte marker, in the supraspinatus muscle (P = .019). PTH increased gene expression of beige adipocyte-related markers and suppressed fat droplet accumulation even after adipogenic differentiation of FAPs (P = .004) but did not reduce fat droplets that had already accumulated in in vitro experiments., Conclusions: PTH facilitated beige adipocyte expression and reversibly ameliorated muscle quality and atrophy following chronic RCT by hindering fat droplet accumulation and facilitating muscle regeneration. Therefore, PTH may be a medical treatment for FI and MA following RCT, leading to expanded rotator cuff repair indications., (Copyright © 2024 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

In East Asia, high levels of atmospheric nitrogen are deposited onto land. This could elevate the nitrate levels in coastal waters via river runoff, even from areas where anthropogenic sources are minimal. It is important to identify NO 3 - sources in river water and the mechanisms involved in NO 3 , K - runoff. Yakushima Island, Japan, is a Natural World Heritage site featuring numerous watersheds with diverse topography and rivers. The area receives significant precipitation, with up to 10 000 mm in mountainous regions. Its proximity to coastal urban areas in China (∼800 km) leads to substantial atmospheric nitrogen wet and dry deposition in the island's forests. The study aimed to clarify regional water quality characteristics by conducting long-term monitoring of dissolved ion components (Na + , K + , Mg 2+ , Ca 2+ , F - , Cl - , NO 3 - , and SO 4 2 - ) in river waters, and to determine the effects of NO 3 - sources and watershed topography on NO 3 - behavior. Dissolved ion concentrations were obtained from a long-term monitoring (2011-2014) dataset. Cluster analysis classified runoff water from the central mountainous region into three groups: western region, other regions, and groundwater. The average NO 3 - concentration in the western region was 10.2 μmol L -1 , which was higher than the 6.24 μmol L -1 observed in the other regions. Stable isotope analysis in December 2018 showed that river water NO 3 - (1.39 μmol L -1 ) in the western region had a high proportion of atmospheric NO 3 - . Topographic analysis indicated that NO 3 - and atmospheric NO 3 - increased in smaller watersheds and steeper terrain. This study conclude that NO 3 - output is controlled by topography., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Plasma is a collection of active particles generated by dissociating molecules and ionizing atoms through applying high energy to a gas, such as high-sound heating or electrical shock. Recently, many reports have been published on the effectiveness of non-thermal atmospheric pressure gas discharge plasma (NTAPP) on living organisms. Furthermore, we have reported on the promotion of bone and tendon repair by NTAPP irradiation. We hypothesized that irradiation of NTAPP would promote the repair of the tendon-bone junction in a rotator cuff repair. This study investigated the effect of NTAPP irradiation on the healing process of the tendon-bone junction., Methods: Among 36 Japanese white rabbits, the infraspinatus tendon was detached from the humeral insertion site. A 3.2 mm bone tunnel was then created at the original insertion site of the infraspinatus muscle. The left shoulder was irradiated with NTAPP at a distance of 1 cm from the bone tunnel for 5 minutes (plasma-treated group), while the right shoulder was not irradiated (control group). The rabbits were sacrificed at 2, 4, and 8 weeks postoperatively, and 6 of each were used for histological evaluation. Mechanical tests were also performed on 6 specimens each at 4 and 8 weeks., Results: Histological evaluation showed that at 4 weeks, the histological tendon to bone maturing score was 6.8 ± 1.3 in the plasma-treated group and 4.8 ± 1.6 in the control group (P < .01); at 8 weeks it was 9.0 ± 1.0 in the plasma-treated group and 5.2 ± 1.1 in the control group (P < .01). Fibrocartilage formation and new bone formation were observed at both 4 and 8 weeks. In the mechanical test, the plasma-treated group had 75.0 ± 18.9 N in ultimate load to failure at 8 weeks. In the control group, it was 51.1 ± 7.9 N. (P = .04)., Conclusion: The repair of the rotator cuff at the tendon-bone junction was significantly improved at 4 and 8 weeks by irradiation with NTAPP., (Copyright © 2024 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

A single-center prospective cohort study was conducted to investigate whether intraocular pressure (IOP)-related 24-h contact lens sensor (CLS) profile parameters can help predict glaucoma progression in patients with normal-tension glaucoma (NTG). CLS measurements (Triggerfish; SENSIMED, Etagnières, Switzerland) at baseline without medication were performed for 24 h in one eye, following diurnal IOP measurements using Goldmann applanation tonometry at 3-h intervals. Glaucoma progression during the follow-up period of ≥ 2 years was determined based on the Guided Progression Analysis of Humphrey visual fields and/or structural progression using fundus photographs. Among 79 patients (mean values: follow-up periods, 48.1 months; age, 51.5 years; baseline IOP, 14.0 mmHg; mean deviation, - 6.04 dB), 23 showed glaucoma progression. A smaller standard deviation of nocturnal ocular pulse amplitude in the CLS profile, a larger range of diurnal IOP at baseline, and the presence of optic disc hemorrhage (DH) during the study period were significant risk factors for glaucoma progression in the multivariate Cox proportional hazards model (hazard ratio, 0.30/mVeq, 1.23/mmHg, and 4.37/presence of DH; P = 0.016, 0.017, and 0.001, respectively). CLS measurements may be useful for assessing the risk of future glaucoma progression in patients with NTG, providing supplementary information to routine IOP measurements., (© 2024. The Author(s).)

Background and Aim: Ustekinumab, a new anti-interleukin-12/23 antibody, is an effective treatment for ulcerative colitis; however, data regarding predictive factors of its efficacy are limited. Predicting treatment efficacy in advance would be useful for selecting a therapeutic agent. This study aimed to identify biomarkers that can predict the long-term outcome of ustekinumab treatment., Materials and Methods: We retrospectively reviewed the records of patients with active ulcerative colitis treated with ustekinumab at Osaka Medical and Pharmaceutical University Hospital from June 2020 to January 2023. We divided patients into non-remission and remission groups, and examined whether baseline biomarkers, including C-reactive protein-to-lymphocyte ratio, and early treatment response could predict clinical remission at week 48 of ustekinumab treatment., Results: Of the 33 patients included in the study, 21 (63.6%) were in clinical remission at week 48 of ustekinumab treatment. Baseline C-reactive protein-to-lymphocyte ratio values were significantly higher in the non-remission than in the remission group. The baseline C-reactive protein-to-lymphocyte ratio value was identified as an independent prognostic factor for clinical remission at week 48 (odds ratio: 10, 95% confidence interval: 1.6-62.4, p = 0.014), with the cutoff value of 3.353 showing excellent prognostic performance (sensitivity: 71.4%, specificity: 83.3%). Furthermore, the clinical response at week 4 (odds ratio: 10, confidence interval: 1.78-56.1, p = 0.009) and that at week 8 (odds ratio: 12, confidence interval: 2.16-66.5, p = 0.005) were significantly associated with clinical remission at week 48., Conclusions: The baseline C-reactive protein-to-lymphocyte ratio value and early treatment response are useful biomarkers to predict the long-term efficacy of ustekinumab treatment., Competing Interests: Shiro Nakamura reports receiving speaking fees from AbbVie GK, EA Pharma Co., Ltd., Mitsubishi Tanabe Pharma Corporation., Mochida Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd, and Janssen Pharmaceutical K.K. Dr., (Copyright: © 2024 Koshiba et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Primary mediastinal germ cell tumor (PMGCT) is an extragonadal germ cell tumor (GCT) that is classified as a poor-prognosis subtype among GCTs. Among them, choriocarcinoma accounts for 2% and its prognosis is considered to be notably poor. The standard treatment for advanced germ cell tumors is BEP therapy (bleomycin, etoposide, cisplatin), followed by surgical resection. However, treatments containing bleomycin are associated with postoperative acute respiratory distress syndrome (ARDS). We report a 38-year-old woman with locally advanced primary mediastinal choriocarcinoma. A computed tomography (CT) of the chest showed a 6.5 cm solid mass in the anterior mediastinum that had invaded the superior vena cava. Laboratory data revealed a serum total human chorionic gonadotropin (hCG) value of 298,220 mIU/mL. After one course of BEP therapy, her total hCG level decreased markedly, and the patient was switched to VIP therapy (etoposide, ifosfamide, cisplatin), a bleomycin-free regimen, to reduce the risk of ARDS. Three courses of VIP therapy and one course of salvage therapy enabled a complete surgical resection without any complications including ARDS. The patient has been disease-free for 16 months since the resection., Supplementary Information: The online version contains supplementary material available at 10.1007/s13691-024-00708-z., Competing Interests: Conflicts of interestThe authors declare that they have no conflict of interest., (© The Author(s) under exclusive licence to The Japan Society of Clinical Oncology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Rolling walkers are common walking aids for individuals with poor physical fitness or balance impairments. There is no doubt that rolling walkers are useful in assisting locomotion. On the other hand, it is arguable that walking with rolling walkers (WW) is effective for maintaining or restoring the nervous systems that are recruited during conventional walking (CW). This is because the differences and similarities of the neural control of these locomotion forms remain unknown. The purpose of the present study was to compare the neural control of WW and CW from the perspective of a split-belt adaptation paradigm and reveal how the adaptations that take place in WW and CW would affect each other. The anterior component of the ground reaction (braking) forces was measured during and after walking on a split-belt treadmill by 10 healthy subjects, and differences in the peak braking forces between the left and right sides were calculated as the index of the split-belt adaptation (the degree of asymmetry). The results demonstrated that (1) WW enabled subjects to respond to the split-belt condition immediately after its start as compared to CW; (2) the asymmetry movement pattern acquired by the split-belt adaptation in one gait mode (i.e., CW or WW) was less transferable to the other gait mode; (3) the asymmetry movement pattern acquired by the split-belt adaptation in CW was not completely washed out by subsequent execution in WW and vice versa. The results suggest unique control of WW and the specificity of neural control between WW and CW; use of the walkers is not necessarily appropriate as training for CW from the perspective of neural control., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The use of thoracic endovascular aortic repair (TEVAR) for thoracic aortic aneurysm (TAA) and Stanford type B aortic dissection (TBAD) has been increasing; however, in terms of etiology, the differences of long term after TEVAR outcomes remain unexplored. Thus, we investigated etiology-specific long-term results of TEVAR for TAA and TBAD. A total of 421 TEVAR procedures were performed at our institution from July 2007 to December 2021; 249 TAA cases and 172 TBAD cases were included. Traumatic aortic dissection and aortic injury cases were excluded. The mean observation duration was 5.7 years. The overall 30-day mortality rate was 1.4% (n = 6), with 1.2% (n = 3) in the TAA group and 1.7% (n = 3) in the TBAD group. The overall incidence of postoperative stroke was 0.9% (n = 4), with 1.2% (n = 3) and 0.6% (n = 1) in the TAA and TBAD groups, respectively (p = 0.90). Paraplegia developed in 1.7% (n = 7) of patients, with 2.4% (n = 6) in the TAA group and 0.6% (n = 1) in the TBAD group. Freedom from aortic-related death was not significantly different between the two etiologies; however, thoracic reintervention was more common in the TBAD group (p = 0.003), with endoleak being the most common indication for reintervention. Additionally, retrograde type A aortic dissection occurred in four TBAD cases, while migration occurred in three TAA cases. The perioperative results of TEVAR for TAA and TBAD were satisfactory. The long-term results were unfavorable owing to the occurrence of etiology-specific and common complications. In terms of the high frequency of reintervention, the long-term complications associated with TEVAR are etiology specific., (© 2024. The Author(s).)

Background: Immune checkpoint inhibitors (ICIs) are crucial in cancer treatment; however, they carry the risk of immune-related adverse events (irAEs), such as enteritis., Case Presentation: This study investigated the role of the gut microbiota during the onset and remission of irAE enteritis in a patient with stage IV melanoma undergoing anti-PD-1 and anti-CTLA-4 therapy. Following commencement of ICI treatment, the patient developed severe diarrhea and was diagnosed with grade 3 irAE enteritis. Steroid and probiotic treatments provided swift symptom relief and remission, as confirmed by reduced fecal calprotectin levels and gastrointestinal imaging. Microbiota diversity analysis conducted via 16S rRNA gene sequencing identified a decrease in Streptococcus prevalence with improvement in enteritis symptoms. Conversely, genera Fusobacterium, Faecalibacterium, Bacteroides, Prevotella, and Bifidobacterium showed increased representation after remission. These genera are associated with anti-inflammatory properties and fibrous substrate degradation, aiding gut health. Immunological assessment demonstrated fluctuations in cytokine expression and the modulation of costimulatory molecules, aligning with therapeutic interventions and microbiota alterations., Conclusions: Our findings indicate a significant correlation between gut microbiota and immune responses in irAE enteritis. This underscores the potential utility of microbiome profiling in predicting irAE occurrence and in providing treatment strategies, thereby promoting a more comprehensive approach to managing the adverse effects of ICIs., (© 2024. The Author(s).)

L-Arabinose (L-Ara) is a plant-specific sugar found in cell wall polysaccharides, proteoglycans, glycoproteins, and small glycoconjugates, which play physiologically important roles in cell proliferation and other essential cellular processes. L-Ara is synthesized as UDP-L-arabinose (UDP-L-Ara) from UDP-xylose (UDP-Xyl) by UDP-Xyl 4-epimerases (UXEs), a type of de novo synthesis of L-Ara unique to plants. In Arabidopsis, the Golgi-localized UXE AtMUR4 is the main contributor to UDP-L-Ara synthesis. However, cytosolic bifunctional UDP-glucose 4-epimerases (UGEs) with UXE activity, AtUGE1, and AtUGE3 also catalyze this reaction. For the present study, we first examined the physiological importance of bifunctional UGEs in Arabidopsis. The uge1 and uge3 mutants enhanced the dwarf phenotype of mur4 and further reduced the L-Ara content in cell walls, suggesting that bifunctional UGEs contribute to UDP-L-Ara synthesis. Through the introduction of point mutations exchanging corresponding amino acid residues between AtUGE1 with high UXE activity and AtUGE2 with low UXE activity, two mutations that increase relative UXE activity of AtUGE2 were identified. The crystal structures of AtUGE2 in complex forms with NAD + and NAD + /UDP revealed that the UDP-binding domain of AtUGE2 has a more closed conformation and smaller sugar-binding site than bacterial and mammalian UGEs, suggesting that plant UGEs have the appropriate size and shape for binding UDP-Xyl and UDP-L-Ara to exhibit UXE activity. The presented results suggest that the capacity for cytosolic synthesis of UDP-L-Ara was acquired by the small sugar-binding site and several mutations of UGEs, enabling diversified utilization of L-Ara in seed plants., (© 2024 The Authors. The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.)

Background: To evaluate the efficacy of a catheter system using a 3-Fr sheath with a steerable microcatheter through right upper limb artery access for superselective intra-arterial cisplatin infusion and concomitant radiotherapy (RADPLAT) to treat right maxillary sinus squamous cell carcinoma (MS-SCC)., Material and Methods: We retrospectively studied 46 sessions in eight patients treated between November 2020 and February 2023 using the catheter system briefly described below. A 3-Fr sheath was inserted into the distal radial, conventional radial, or brachial arteries. A coaxial catheter system with a 2.9-Fr steerable microcatheter and a 1.9-Fr microcatheter was advanced into the brachiocephalic artery. The right common carotid artery was selected by bending the tip of the steerable microcatheter. Coil embolization and intra-arterial cisplatin infusion after selecting each external carotid artery branch were achieved using this catheter system., Results: Cisplatin infusion and coil embolization were successful in all sessions. Arterial occlusion at the sheath insertion sites was found in 29.4% (5/17) of the distal radial arteries and 33.3% (3/9) of the conventional radial arteries. No other major complications were observed during the procedure., Conclusion: Using a 3-Fr catheter system with a steerable microcatheter through right upper limb artery access is a feasible method for RADPLAT in treating right MS-SCC.

Background Motivation dysregulation is common in several psychiatric disorders. However, little is known about the relationships between motivation and the regional brain areas involved. We evaluated the relationships between brain microstructural features and causality orientation in patients with schizophrenia, major depressive disorder (MDD), and bipolar disorder (BD) using diffusional kurtosis imaging (DKI) techniques. Methods Forty patients with MDD, 36 with BD, and 30 with schizophrenia underwent DKI and assessment using the General Causality Orientation Scale (GCOS). We analyzed the DKI index and the GCOS subscales. Results The psychiatric patients showed significant positive correlations between the GCOS-autonomy orientation score and the mean kurtosis (MK) values in the prefrontal regions, orbitofrontal regions, and posterior cingulate cortex. When the analyses were performed separately by disease and gender, a positive correlation was found between the GCOS-autonomy orientation score and the MK values in the left prefrontal regions transdiagnostically, especially among female patients with MDD, BD, and schizophrenia. Conclusions A similar association between intrinsic motivation and MK value in the left prefrontal cortex was suggested in patients with schizophrenia, MDD, and BD. The commonality of this association among these disorders might lead to the discovery of a new biomarker for psychiatric clinical research., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Ota et al.)

Electroencephalogram (EEG) electrode digitization is crucial for accurate EEG source estimation, and several commercial systems are available for this purpose. The present study aimed to evaluate the digitizing accuracy of electromagnetic and optical systems. Additionally, we introduced a novel rotation method for the electromagnetic system and compared its accuracy with the conventional method of electromagnetic and optical systems. In the conventional method, the operator moves around a stationary participant to digitize, while the participant does not move their head or body. In contrast, in our proposed rotation method with an electromagnetic system, the operator rotates the participant sitting on a swivel chair to digitize in a consistent position. We showed high localization accuracy in both the optical and electromagnetic systems, with an average localization error of less than 3.6 mm. Comparisons of the digitization methods revealed that the electromagnetic system demonstrates superior digitizing accuracy compared to the optical system. Notably, the proposed rotational method is the most accurate among the three methods, which can be attributed to the consistent positioning of EEG electrode digitization within the electromagnetic field. Considering the affordability of the electromagnetic system, our findings provide valuable insights for researchers aiming for precise EEG source estimation.•The study compares the accuracy of electromagnetic and optical systems for EEG electrode digitization, introducing a novel rotation method for improved consistency and precision.•The electromagnetic system, especially with the proposed rotation method, achieves superior digitizing accuracy over the optical system.•Highlighting the cost-effectiveness and precision of the electromagnetic system with the rotation method, this research offers significant insights for achieving precise EEG source estimation., 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., (© 2024 The Author(s).)

Background: Endoscopic mucosal healing serves as a critical predictor for achieving long-term remission in Crohn's disease treatment. Recent data indicate that the effectiveness of healing varies based on the location of gastrointestinal inflammation. Additionally, reports suggest that antitumor necrosis factor-α (anti-TNF-α) agents exhibit reduced efficacy in treating small intestinal inflammation compared to colorectal inflammation. Conversely, limited research exists regarding the impact of the anti-IL12/23 agent ustekinumab (UST) on small intestinal inflammation. This study aimed to compare the effects of anti-TNF-α agents and UST on small intestinal inflammation using propensity score analysis., Methods: This retrospective observational study involved 70 patients with Crohn's disease who had inflammation in the small intestine and had initiated treatment with either anti-TNF agents or UST between March 2015 and August 2021. Endoscopic findings were evaluated before treatment commencement and at 1-2 years post-treatment initiation. The propensity score was employed to compare the efficacy of TNF agents and UST on small bowel inflammation., Results: Ustekinumab exhibited greater improvement in the small intestinal endoscopy score than anti-TNF-α antibodies according to the propensity score analysis (inverse probability weighting; P  = .0448). However, no significant disparity was observed in the overall improvement of endoscopic scores between UST and anti-TNF-α antibodies ( P  = .5938)., Conclusions: This study suggests that UST might be more effective than anti-TNF-α agents in treating small intestinal inflammation in Crohn's disease., Competing Interests: The authors declare no conflicts of interest regarding this article. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)