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Nuclear kinetic calculations based on point kinetic model have been generally applied as the standard method for neutronics codes. As the central control rod (C-CR) withdrawal test has demonstrated in a prismatic core type high-temperature gas-cooled reactor (HTGR) named High Temperature Engineering Test Reactor (HTTR), the transient calculation of kinetic parameter, reactivity, and neutron fluxes, requires a new method to shorten calculation-process time. Development of neural network method was applied to point kinetic model as the necessity of real-time calculation that could work in parallel with the digital reactivity meter. The combination of Time Delayed Neural Network (TDNN) and Jordan Recurrent Neural Network (Jordan RNN) named TD-Jordan RNN was the result of the modeling approach. The application of TD-Jordan RNN with adequate learning, tested offline, determined results accurately even when signal inputs were noisy. Furthermore, the preprocessing for neural network input utilized noise reduction as one of the equations to transform two of twelve time-delayed inputs into power corrected inputs.

In Japan, the 7-valent pneumococcal conjugate vaccine (PCV7) was introduced to the nation's routine immunization program in April 2013 and was replaced by the 13-valent pneumococcal conjugate vaccine (PCV13) in November 2013. Distribution of serotypes and macrolide resistance genotypes was investigated for a total of 1097 (975 children, 122 adults) and 960 (873 children, 87 adults) clinical isolates of Streptococcus pneumoniae from noninvasive infections in Hokkaido (northern main island of Japan) in the routine immunization periods for PCV7 and PCV13 (April–October 2013 and November 2013–November 2014, respectively). Serotype was determined by sequential multiplex PCR and additional genetic analyses. Macrolide resistance genes erm(B) and mef(A/E) were detected by multiplex PCR. Although the most prevalent serotypes in children were 23A and 6C in the PCV7 period, after replacement with PCV13, 19A became the most common, followed by 6C, 15A and 23A. Among adults, serotype 3 was consistently the most frequent throughout the study periods. Compared with values from the pre-PCV7 routine immunization period, PCV7 serotypes decreased from 48.3 to 3.3% in the PCV13 period among children, while the rates of non-PCV13 serotypes (particularly 15A, 23A, 11A, 10A and 35B) increased from 39.7 to 75.1% (p

Abstract  A fatal case of intentional poisoning with two antiarrhythmic agents, pilsicainide, a pure sodium channel blocker, and atenolol, a selective β1 blocker, is presented. A woman in her twenties was found dead at home and empty pill packages of pilsicainide, atenolol, and aspirin were found near by. Hesitation marks were found on the wrist, and strong fibrous degeneration was observed in the cardiomyocytes of the sinoatrial node. The blood concentrations of pilsicainide and atenolol were 7.83 and 4.94 μg/ml, respectively, both far above the reported therapeutic levels. According to these results, we concluded that death was due to cardiac arrhythmia caused by poisoning with pilsicainide and atenolol. This is the first report of fatal poisoning attributable to an overdose of the combination of these two antiarrhythmic drugs. [ABSTRACT FROM AUTHOR]

We have developed a 1310-nm uncooled electroabsorption modulator integrated light source (EML) with an AlGaInAs multiple quantum well (MQW) active/absorption stripe, which was simultaneously grown using the narrow-stripe selective MOVPE technique and was buried with an Fe-doped InP. The Al-content MQW oxidation was effectively inhibited by using the same technique. An experiment-based evaluation of the device's performance revealed that by only changing the modulation bias voltage linearly with temperature, it was possible to achieve 10-Gb/s penalty-free operation at up to 85°C over a 23-km single-mode fiber. [ABSTRACT FROM PUBLISHER]

A compact full C-band external cavity wavelength tunable laser is proposed. The cavity contains a fixed etalon and makes use of a liquid-crystal-based tunable mirror. The measurement results show a tuning range of 35 nm with fiber coupled power of more than 15 dBm. The sidemode suppression ratio is higher than 50 dB over the whole range and the relative intensity noise is below -148 dB/Hz. The linewidth is in worst case 700 kHz. [ABSTRACT FROM PUBLISHER]

An advanced microarray-selective epitaxy with wider open-stripes has been developed for simple fabrication of distributed-feedback laser diode array-based high-power wavelength-selectable light sources. More than 40-mW fiber-coupled power and 50-dB sidemode suppression ratio over 9.2-nm wavelength were achieved. [ABSTRACT FROM PUBLISHER]

We report on the first demonstrated near-complete coverage of the S-, C-, and L-bands using six different ranges of wavelength-selectable microarray light sources (WSLs) based on a distributed-feedback (DFB) laser diode (LD) array. The six devices were fabricated on only two wafers. Each device has a tuning range of more than 15 nm, a sidemode suppression ratio of over 40 dB, and a fiber-coupled power greater than around 10 mW. [ABSTRACT FROM PUBLISHER]

A wide-band wavelength-selectable light source module having an integrated multiwavelength locker has been developed. An eight-distributed-feedback (DFB) arrayed monolithic light source was designed to have 40-nm tunable range in the L-band by covering 5 nm per DFB laser diode. A uniquely designed etalon-based wavelength locker achieved very stable operation and uniform locking performance for all channels. Wavelength variation in the short term at room temperature was much less than 1 pm and the locked wavelength stayed within +/-5 pm when the case temperature of the module was varied from -20°C to 65°C. [ABSTRACT FROM PUBLISHER]

We have studied the local structure of Ca0.9Pr0.1Fe2As2, showing filamentary superconductivity above 40 K, by a combined analysis of Fe K-edge and As K-edge extended x-ray absorption fine structure measurements. The experiments are performed as a function of temperature exploiting a single crystal sample and in-plane polarization of the x-ray beam to extract information on the directional displacements. The local structure of the FeAs layer is found to be consistent with a regular FeAs4 tetrahedron containing negligible local disorder. Unlike other superconducting systems, we do not find any change in the atomic displacements across the superconducting transition temperature. The results are compatible with electron doping induced intrinsic superconductivity of optimized FeAs4 local structure containing negligible disorder. [ABSTRACT FROM AUTHOR]

We have studied local structure of IrTe2 by Ir L3-edge extended x-ray absorption fine structure (EXAFS) measurements as a function of temperature to investigate origin of the observed structural phase transition at Ts ∼ 270 K. The EXAFS results show an appearance of longer Ir-Te bond length (▵ R ∼ 0.05 Å) at T < Ts. We have found Ir-Ir dimerization, characterized by distinct Ir-Ir bond lengths (▵R ∼ 0.13 Å), existing both above and below Ts. The results suggest that the phase transition in IrTe2 should be an order-disorder-like transition of Ir-Ir dimers assisted by Ir-Te bond correlations, thus indicating important role of the interaction between the Ir 5d and Te 5p orbitals in this transition. [ABSTRACT FROM AUTHOR]

The separation of the acetate derivatives of a number of oxygenated sterols was achieved by medium pressure liquid chromatography on silica gel columns and by normal and reversed phase high performance liquid chromatography. We have explored the application of these chromatographic systems for the analysis of oxygenated sterols of plasma samples from two normal human subjects. The addition of highly purified [14C]cholesterol to plasma permitted the detection and quantitation of oxygenated sterols formed by autoxidation of cholesterol during processing of the samples. Special attempts to suppress autoxidation of cholesterol included the use of an all-glass closed system for saponification and extraction under argon followed by rapid removal of cholesterol from the polar sterols by reversed phase medium pressure liquid chromatography. Chromatographic analyses of the [3H]acetate derivatives of the polar sterols provided a sensitive approach for the detection and quantitation of the individual oxygenated sterols. Oxygenated sterols detected in plasma included cholest-5-ene-3 beta,26-diol, (24S)-cholest-5-ene-3 beta,24-diol, and cholest-5-ene-3 beta,7 alpha-diol. After correction for their formation by autoxidation of cholesterol during processing of the samples, very little or none of the following sterols were observed: cholest-5-ene-3 beta,7 beta-diol, 5 alpha,6 alpha-epoxy-cholestan-3 beta-ol, 5 beta,6 beta-epoxy-cholestan-3 beta-ol, and cholestane- 3 beta, 5 alpha,6 beta-triol, and the 25-hydroxy, 22R-hydroxy, 21-hydroxy, 20 alpha-hydroxy, and 19-hydroxy derivatives of cholesterol.

The aquaporin-4 (AQP4) water channel is essential in neurofluid dynamics. AQP4 loss impairs solute exchange between the cerebrospinal fluid (CSF) and interstitial fluid (ISF). However, whether AQP4 expression affects solute clearance from the CSF space to the extracranial space remains unclear. This study aimed to investigate this using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) following the intrathecal administration of gadolinium-based contrast agents (GBCAs) to AQP4 knockout (KO) rats. AQP4 KO rats showed reduced efflux of intrathecal GBCAs to the extracranial spaces through CSF drainage pathways and increased retention of intrathecal GBCAs in the CSF space compared with the controls. These results suggest that AQP4 loss impairs solute clearance from the CSF space to the extracranial spaces via the CSF drainage pathways. This study revealed a close relationship between AQP4 expression and CSF solute clearance, contributing to a better understanding of the function of AQP4 in neurofluid dynamics., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

The International Commission on Radiological Protection recommended a significant reduction of the equivalent dose limit for the eye lens. Reportedly, medical staff in charge of diagnostic imaging procedures may exceed the new dose limits for the eye lens. The use of dosimeters dedicated to the eye lens remains low, and dosimeters for the neck region were often used to assess eye lens doses. However, measurements by neck badges may overestimate or underestimate the recommended eye lens doses because the height of the neck differs from that of the eye. This study aimed to evaluate the air dose distribution in the vertical plane to understand the difference between neck and eye doses. H*(10) in the height of the eye position was 52.8% lower than that in the height of the neck position in the under-table position. Thus, the equivalent eye lens dose evaluated using a neck badge dosimeter may be overestimated., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Contemporary thrombolytics in acute ischemic stroke are limited to administration within 4.5 hours of last known normal. JX10 (formerly TMS-007), a Stachybotrys microspora triprenyl phenol family member, may extend this therapeutic window., Methods: In this multicenter, randomized, double-blind, placebo-controlled, dose-escalation phase 2a study, JX10 or placebo was administered as a single intravenous infusion to Japanese patients with acute ischemic stroke who were unable to receive tissue-plasminogen activator or thrombectomy within 12 hours of last known normal. Primary end point was incidence of symptomatic intracranial hemorrhage with a worsening National Institutes of Health Stroke Scale score of ≥4 points within 24 hours of drug administration (symptomatic intracranial hemorrhage incidence)., Results: Ninety patients received either placebo (n=38; female 26.3%) or JX10 at 1, 3, or 6 mg/kg (n=6, 18, 28; female 0%, 33.3%, and 42.9%, respectively). Median age (range) and baseline median (range) National Institutes of Health Stroke Scale scores were respectively 76.5 (42-87) and 8 (6-21) for the combined JX10 cohort (JX10 Cohorts) and 75.0 (34-85) and 8 (6-22) for placebo. Median (range) dosing time since last known normal was 9.5 (5.0-12.1) and 10.0 (3.7-12.0) hours for JX10 Cohorts and placebo, respectively. Symptomatic intracranial hemorrhage incidence was 0% (0/52 [95% CI, 0.0-5.6]) for JX10 Cohorts versus 2.6% (1/38 [95% CI, 0.1-13.8]) for placebo ( P =0.42). Vessel patency at 24 hours (secondary end point) in patients with baseline arterial occlusive lesion score <3 (39/90) improved in 58.3% (14/24) of patients in JX10 Cohorts versus 26.7% (4/15) for placebo (odds ratio, 4.23 [95% CI, 0.99-18.07]). In JX10 Cohorts, a significantly higher proportion of patients had modified Rankin Scale scores of 0 to 1 on day 90 (secondary end point) versus placebo (JX10: 21/52, 40.4% versus placebo: 7/38, 18.4%; P =0.03)., Conclusions: JX10 was well tolerated and may expand the acute ischemic stroke therapeutic window as a novel thrombolytic agent., Registration: URL: https://rctportal.niph.go.jp/en; Unique identifier: jRCT2080223786.

Introduction: Immune checkpoint inhibitors (ICIs) plus chemotherapy is now a standard treatment for non-small cell lung cancer (NSCLC). Whether ICI plus chemotherapy (ICI-chemo) or ipilimumab plus nivolumab (I-N)-based therapy is superior for patients with NSCLC with a programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) of 1-49 % has not been evaluated., Methods: This multicenter retrospective study included NSCLC patients with a TPS score of 1-49 %, who began first-line chemotherapy. Propensity score matching analysis was used to adjust for various confounders and evaluate treatment efficacy., Results: A total of 401 patients were enrolled, of whom 308 received ICI-chemo and 93 received I-N-based therapy. The median OS was 21.0 months in the ICI-chemo group and 20.0 months in the I-N-based therapy group. After propensity score matching, there was no difference in OS or PFS between the ICI-chemo group and the I-N-based therapy group (OS: hazard ratios (HR), 0.83; 95 % confidence interval [CI], 0.54-1.26, PFS: HR, 0.72; 95 % CI, 0.52-1.00). Among PD-L1 TPS 25-49 %, there was a tendency for OS to be favorable for the ICI-chemo group (OS: HR, 0.30; 95 % CI, 0.09-0.85). Treatment discontinuation occurred for 26.2 % of the patients in the ICI-chemo group and 41.9 % in the I-N-based therapy group., Conclusions: Among PD-L1 TPS 1-49 %, there was no significant difference in survival outcomes between the ICI-chemo group and the I-N-based therapy group. Based on the results of a subgroup analysis, ICI-chemo may be superior for treating NSCLC with a TPS of 25-49 %., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Tanaka reported receiving lecture fees from AstraZeneca K.K, Chugai Pharmaceutical Co., Boehringer-Ingelheim Japan Inc., Ono Pharmaceutical Co., Pfizer Japan Inc., and Bristol-Meyers Squibb. Dr. Makiguchi reported receiving honoraria from Asahi KASEI, Boehringer-Ingelheim Japan, Inc., AstraZeneca K.K, Eli Lilly, GlaxoSmithKline, Ono Pharmaceutical Co., Teijin Pharma, Taiho Pharmaceutical, Chugai Pharmaceutical Co., and LTD. Dr. Tozuka reported receiving honoraria from AstraZeneca and Chugai Pharmaceutical Co. Dr. Kawashima reported receiving honoraria from AstraZeneca K.K, Chugai Pharmaceutical Co, Taiho Pharmaceutical, Eli Lilly, Kyowa Hakko-Kirin, and Life Technologies Japan Ltd. Dr. Koyama reported receiving honoraria from AstraZeneca K.K. and Chugai Pharmaceutical Co. Dr. Tambo reported receiving honoraria from Chugai Pharmaceutical Co, Taiho Pharmaceutical, MSD K.K, and the Daiichi Sankyo Company. Dr. Ogusu reported receiving speakers’ bureau from MSD K.K, Bristol-Meyers Squibb, and Chugai Pharmaceutical Co. Dr. Hasegawa reported receiving honoraria from AstraZeneca K.K, Chugai Pharmaceutical Co., Eli Lilly, and Merck. Dr. Miyauchi reported receiving honoraria from AstraZeneca, Eli Lilly, Chugai Pharmaceutical Co, Boehringer-Ingelheim Japan, Inc., Taiho Pharmaceutical, Kyowa Hakko-Kirin, Daiichi-Sankyo, MSD, Bristol Myers Squibb, Merck, Amgen, Ono Pharmaceutical Co., Thermo Fisher Scientific, Nippon Kayaku, Takeda Pharmaceutical Co., and Sysmex. He received advisory roles from Boehringer-Ingelheim Japan Inc., Ono Pharmaceutical Co, Daiichi-Sankyo, and Merck outside of the submitted work. Dr. Sakatani reported receiving speakers’ bureau from AstraZeneca, Eli Lilly, MSD K.K, Boehringer-Ingelheim Japan, Inc., Takeda Pharmaceutical Co., Taiho Pharmaceutical, and Bristol Myers Squibb. Dr. Tsuchiya-Kawano reported receiving speakers’ bureau from Bristol Myers Squibb, AstraZeneca, Taiho Pharmaceutical, Chugai Pharmaceutical Co., MSD K.K, Ono Pharmaceutical Co., and Kyowa Hakko-Kirin. Dr. Nishio reported receiving honoraria from Pfizer Japan Inc, Bristol Myers Squibb, Ono Pharmaceutical Co., Chugai Pharmaceutical Co., Taiho Pharmaceutical, AstraZeneca, Boehringer-Ingelheim Japan, Inc., MSD K.K, Novartis, Eli Lilly, Nippon Kayaku, Takeda Pharmaceutical Co., Merck, Janssen, Amgen, Eisai, and Daiichi-Sankyo. He received research funding from Pfizer Japan Inc, Bristol Myers Squibb, Taiho Pharmaceutical, AstraZeneca, MSD K.K, Takeda Pharmaceutical Co, Merck, Janssen, and Amgen, outside of the submitted work. All remaining authors have declared no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Tau aggregation is a defining feature of neurodegenerative tauopathies, including Alzheimer's disease, corticobasal degeneration, and frontotemporal dementia. This aggregation involves the liquid-liquid phase separation (LLPS) of Tau, followed by its sol-gel phase transition, representing a crucial step in aggregate formation both in vitro and in vivo. However, the precise cofactors influencing Tau phase transition and aggregation under physiological conditions (e.g., ion concentration and temperature) remain unclear. In this study, we unveil that nucleic acid secondary structures, specifically RNA G-quadruplexes (rG4s), and calcium ions (Ca 2+ ) synergistically facilitated the sol-gel phase transition of human Tau under mimic intracellular ion conditions (140 mM KCl, 15 mM NaCl, and 10 mM MgCl 2 ) at 37°C in vitro. In the presence of molecular crowding reagents, Tau formed stable liquid droplets through LLPS, maintaining fluidity for 24 h under physiological conditions. Notably, cell-derived RNA promoted Tau sol-gel phase transition, with rG4s emerging as a crucial factor. Surprisingly, polyanion heparin did not elicit a similar response, indicating a distinct mechanism not rooted in electrostatic interactions. Further exploration underscored the significance of Ca 2+ , which accumulate intracellularly during neurodegeneration, as additional cofactors in promoting Tau phase transition after 24 h. Importantly, our findings demonstrate that rG4s and Ca 2+ synergistically enhance Tau phase transition within 1 h when introduced to Tau droplets. Moreover, rG4-Tau aggregates showed seeding ability in cells. In conclusion, our study illuminates the pivotal roles of rG4s and Ca 2+ in promoting Tau aggregation under physiological conditions in vitro, offering insights into potential triggers for tauopathy., Competing Interests: Competing interests The authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Visuospatial perception is often impaired in people with Alzheimer's disease (AD). Because visuospatial information is thought to be processed in the visual dorsal stream, it is believed that brain activities in the dorsal stream will be altered in AD patients. In this study, we investigated whether regional brain activity related to visuospatial perception were associated with AD progression markers. An optic-flow task, which activates the dorsal stream associated with visuospatial perception, was performed, and the brain activities evoked by the task were evaluated using magnetoencephalography (MEG). First, we evaluated the responses to optic-flow stimuli in 21 cognitively unimpaired participants and determined the regions of interest (ROIs) where optic-flow activities were activated. Task-related activations were observed in 14 cortical regions including the dorsal stream: the right and left medial ventral occipital cortex (MVOcC), lateral occipital cortex (LOcC), precuneus (Pcun), inferior parietal lobule (IPL), superior parietal lobule (SPL), posterior superior temporal sulcus (pSTS), and fusiform gyri (FuG). Next, we performed correlation analyses between task-related activity in each ROI and two AD progression markers, global amyloid burden and parahippocampal gyrus (PHG) volume, for 25 participants who underwent amyloid positron emission tomography (PET) scans. We found that the global amyloid burden was negatively correlated with task-related activity in the left MVOcC and right SPL [r = -0.488 (p = 0.013) and r = -0.421 (p = 0.038), respectively]. Furthermore, significant positive correlations were observed between PHG volume and task-related activity in both the left and right SPL [r = 0.500 (p = 0.011) and r = 0.549 (p = 0.005), respectively]. Since the SPL is known to be responsible for visuospatial perception, these results suggest that MEG neuronal activity of patients performing the optic-flow activity can detect changes in brain activity associated with visuospatial impairment related to AD., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ST, KK, HM, YM and TA are employees of Ricoh Company, Ltd. The authors declare that no other competing interests exist. The other authors have no competing financial conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

A 70-year-old woman with anti-aminoacyl-tRNA synthetase (ARS) antibody-positive interstitial lung disease (ARS-ILD) received daily medications and regular cyclophosphamide cycles for recurring exacerbations. Approximately four years after immunosuppression initiation, the patient was admitted for progressive dyspnea on exertion. Chest computed tomography (CT) findings were suggestive of acute exacerbation. Despite intensified immunosuppressive treatment, the radiographic findings worsened, and serum Krebs von den Lungen-6 (KL-6) levels increased. A bronchoalveolar lavage fluid (BALF) examination revealed amorphous globules and alveolar macrophages with eosinophilic granules. Owing to negative anti-granulocyte-macrophage colony-stimulating factor antibody tests, a diagnosis of secondary pulmonary alveolar proteinosis (PAP) was established.

Background: The stability of antimicrobials in peritonitis during peritoneal dialysis (PD) solutions is a critical factor influencing treatment success. This study investigated the stability of daptomycin (DAP) when combined with icodextrin-based PD solution, by measuring DAP concentrations and observing any structural changes., Methods: A dose of DAP (350 mg) was dissolved in 7 mL of saline in a clean bench. The solution was then injected into the large compartment (1,260 mL) of NICOPELIQ ® Peritoneal Dialysis Solution and thoroughly mixed. Samples were collected at intervals ranging from 0 to 336 h (7 points in total). The concentration of DAP was quantified using high-performance liquid chromatography (HPLC). The structure of any unidentified peaks was determined using HPLC coupled with electrospray ionization tandem mass spectrometry., Results: DAP maintained 90% of the initial concentration in NICOPELIC ® for 72 h at room temperature and 12 h at 37 °C. Unidentified peaks, distinct from DAP, were detected during analysis. Further investigation indicated that these peaks corresponded to anhydrated DAP., Conclusions: The findings from this stability study are expected to enhance the effectiveness of outpatient management and preparation for treating peritonitis using DAP., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Synucleinopathies, including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy, are triggered by α-synuclein aggregation, triggering progressive neurodegeneration. However, the intracellular α-synuclein aggregation mechanism remains unclear. Herein, we demonstrate that RNA G-quadruplex assembly forms scaffolds for α-synuclein aggregation, contributing to neurodegeneration. Purified α-synuclein binds RNA G-quadruplexes directly through the N terminus. RNA G-quadruplexes undergo Ca 2+ -induced phase separation and assembly, accelerating α-synuclein sol-gel phase transition. In α-synuclein preformed fibril-treated neurons, RNA G-quadruplex assembly comprising synaptic mRNAs co-aggregates with α-synuclein upon excess cytoplasmic Ca 2+ influx, eliciting synaptic dysfunction. Forced RNA G-quadruplex assembly using an optogenetic approach evokes α-synuclein aggregation, causing neuronal dysfunction and neurodegeneration. The administration of 5-aminolevulinic acid, a protoporphyrin IX prodrug, prevents RNA G-quadruplex phase separation, thereby attenuating α-synuclein aggregation, neurodegeneration, and progressive motor deficits in α-synuclein preformed fibril-injected synucleinopathic mice. Therefore, Ca 2+ influx-induced RNA G-quadruplex assembly accelerates α-synuclein phase transition and aggregation, potentially contributing to synucleinopathies., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: This study examined the impact of the Center of Healthy Aging Program (CHAP) on the cognitive function and economic burden associated with dementia., Methods: This observational study utilised Iwaki cohort data. We included participants with mini-mental state examination (MMSE) scores and categorised them into pre- and post-CHAP groups based on their year of entry into the cohort (before 2013 or after) (index year). We defined participants with suspected severe cognitive impairment and suspected mild cognitive impairment using their MMSE scores, with their incidence being the first observation meeting these definitions during the follow-up period. We compared the incidence rates between the pre- and post-CHAP groups using Cox proportional hazard analysis. Medical and caregiving costs were estimated based on the projected number of residents in Iwaki area with suspected mild cognitive impairment and sSCI during hypothetical 10 years of the CHAP implemented or not and compared., Results: Of the 2,569 participants, 1716 and 853 were included in the pre- and post-CHAP groups, respectively. The incidence rate of suspected mild cognitive impairment was significantly lower in the post-CHAP group even after adjusted known factors associated with cognitive disorders. No cases of suspected severe cognitive impairment occurred in the post-CHAP group during the follow-up period. Estimated costs of JPY 1,628,450 (USD 11562.00 or EUR 10259.24, JPY 100  =  USD 0.71 or EUR 0.63) and JPY 789,560 (USD 5605.88 or EUR 4974.23) per person per year were projected after 10 years with and without the CHAP, respectively., Conclusions: We demonstrated a reduction in the incidence rate of suspected mild cognitive impairment among residents who participated in the CHAP and a decrease in the medical and caregiving costs associated with suspected severe cognitive impairment., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: AS was an employee of Medilead, Inc. and serves as a director of Healthcare Consulting, Inc. KK holds the position of Executive Vice President of Integrated Clinical Care Informatics, Inc. AI received grants from Abbott Japan Inc., Abbvie G.K., Becton, Dickinson and Company, Creative-Ceuticals Inc., Eli Lilly Japan K.K., Gilead Sciences K.K., Intuitive Surgical G.K., Milliman Inc., Pfizer Inc., Sanofi Pasteur Inc., and Terumo Corporation, and personal fees from Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd., CSL Behring Japan Inc., FUJIFILM Corporation, Sanofi K.K., and Takeda Pharmaceutical Co., Ltd. outside the submitted work., (Copyright: © 2024 Shoji 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.)

Background: Management of patients with colorectal liver metastases (CRLMs) requires a multidisciplinary approach. For patients with progression of RAS mutant tumors, the choice of angiogenesis inhibitors can be controversial. Here, we report a patient with RAS mutant CRLMs achieving long-term disease-free survival with repeated R0 resections and perioperative treatment, especially aflibercept + FOLFIRI (5-fluorouracil, levofolinate, irinotecan), which may have prevented long-term recurrence., Case Presentation: The patient was a 37 year-old woman diagnosed with RAS mutant transverse colon cancer with 19 LMs. As the metastases were limited to the liver, we introduced systemic chemotherapy aiming at conversion surgery. After six cycles of bevacizumab + FOLFOXIRI (5-fluorouracil, levofolinate, oxaliplatin, irinotecan), we performed partial hepatectomy for all LMs, and left hemicolectomy for the primary tumor after another four cycles of bevacizumab + FOLFIRI. Three months after surgery, the patient presented with massive ovarian metastases with carcinomatous ascites. We conducted bilateral oophorectomy, and initiated aflibercept + FOLFIRI therapy considering the possibility of resistance to bevacizumab. The patient was recurrence-free for 2 years during aflibercept + FOLFIRI treatment. After its discontinuation, two distant metastases developed. Both were resectable and the patient achieved recurrence-free survival of 2 years and 3 months after the last operation (6 years since initiation of treatment), without additional chemotherapy., Conclusions: We believe that multidisciplinary treatment aimed at complete resection could lead to long-term survival even in patients with repeated recurrence of CRLMs. Aflibercept + FOLFIRI could be effective in controlling metastasis of RAS mutant colon cancer even after treatment with bevacizumab., (© 2024. The Author(s).)

A correct perception of one's own abilities is essential for making appropriate decisions. A well-known bias in probability perception is that rare events are overestimated. Here, we examined whether such a bias also exists for action outcomes using a simple reaction task. In Experiment 1, after completing a set of 30 trials of the simple reaction task, participants were required to judge the probability that they would be able to respond before a given reference time when performing the task next. We assessed the difference between the actual reaction times and the probability judgement and found that the represented probability distribution was more widely distributed than the actual one, suggesting that low-probability events were overestimated and high-probability events were underestimated. Experiment 2 confirmed the presence of such a bias in the representation of both one's own and another's reaction times. In addition, Experiment 3 showed the presence of such a bias regardless of the difference between the representation of another's reaction times and the mere numerical representation. Furthermore, Experiment 4 found the presence of such a bias even when the information regarding actual reaction times was visually shown before the representation. The present results reveal the existence of a highly robust bias in the representation of motor performance, which reflects the ubiquitous bias in probability perception and is difficult to eliminate., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To investigate whether deep cervical lymph node (DCLN) ligation alters intracranial cerebrospinal fluid (CSF) tracer dynamics and outflow using a rat model with intrathecal dynamic contrast-enhanced (DCE) MRI., Methods: Six bilateral DCLN-ligated and six sham-operated rats were subjected to DCE MRI with Gd-BTDO3A, and dynamic T1-weighted images were acquired. ROIs were collected from the CSF at the C1 level (CSF&#95;C1), CSF between the olfactory bulbs (CSF&#95;OB), CSF at the pituitary recess (CSF&#95;PitR), and CSF at the pineal recess (CSF&#95;PinR), upper nasal turbinate (UNT), olfactory bulbs, cerebrum, and the jugular region. Time-intensity curves were evaluated, and the maximum slope, peak timing, peak signal ratio, and elimination half-life for the four CSF ROIs and UNT were calculated and compared., Results: Delayed tracer arrival in the rostral CSF space and the nasal cavity with tracer retention in the ventral CSF space were observed in the ligation group. The maximum slopes were smaller in the ligation group at UNT (sham: 0.075 ± 0.0061, ligation: 0.044 ± 0.0086/min, P = 0.011). A significant difference was not detected in peak timings. The peak signal ratio values were lower in the ligation group at UNT (sham: 2.12 ± 0.19, ligation: 1.72 ± 0.11, P = 0.011). The elimination half-life was delayed in the ligation group at CSF&#95;C1 (sham: 30.5 ± 2.70, ligation: 44.4 ± 12.6 min, P = 0.043), CSF&#95;OB (sham: 30.2 ± 2.67, ligation: 44.8 ± 7.47 min, P = 0.021), and CSF&#95;PitR (sham: 30.2 ± 2.49, ligation: 41.3 ± 7.57 min, P = 0.021)., Conclusion: The DCLN ligation in rats blocked CSF outflow into the nasal cavity and caused CSF retention.

A woman in her mid-60s with recurrent polychondritis was admitted to our hospital due to airway stenosis secondary to an uncovered metallic stent. She underwent a bronchoscopic intervention under general anaesthesia. During the procedure, the stent fracture was cauterized using Argon Plasma Coagulation (APC) cauterisation, performed with argon flow at 1 L/min and power set at 70 W. APC cauterisation caused the stent wire to flex circularly, gradually improving the stenosis. Tracheal dilatation was then performed using an airway balloon. Following the ballooning, a thin bronchoscope was easily passed through the lower trachea, and the left and right main bronchi were observed; therefore, the procedure was completed without any complications. APC coagulation and airway ballooning are viable choices for the temporary treatment of airway stenosis due to broken metallic stents., Competing Interests: None declared., (© 2024 The Author(s). Respirology Case Reports published by John Wiley & Sons Australia, Ltd on behalf of The Asian Pacific Society of Respirology.)

Purpose: To evaluate deep learning-reconstructed (DLR)-fluid-attenuated inversion recovery (FLAIR) images generated from undersampled data, compare them with fully sampled and rapidly acquired FLAIR images, and assess their potential for white matter hyperintensity evaluation., Materials and Methods: We examined 30 patients with white matter hyperintensities, obtaining fully sampled FLAIR images (standard FLAIR, std-FLAIR). We created accelerated FLAIR (acc-FLAIR) images using one-third of the fully sampled data and applied deep learning to generate DLR-FLAIR images. Three neuroradiologists assessed the quality (amount of noise and gray/white matter contrast) in all three image types. The reproducibility of hyperintensities was evaluated by comparing a subset of 100 hyperintensities in acc-FLAIR and DLR-FLAIR images with those in the std-FLAIR images. Quantitatively, similarities and errors of the entire image and the focused regions on white matter hyperintensities in acc-FLAIR and DLR-FLAIR images were measured against std-FLAIR images using structural similarity index measure (SSIM), regional SSIM, normalized root mean square error (NRMSE), and regional NRMSE values., Results: All three neuroradiologists evaluated DLR-FLAIR as having significantly less noise and higher image quality scores compared with std-FLAIR and acc-FLAIR (p < 0.001). All three neuroradiologists assigned significantly higher frontal lobe gray/white matter visibility scores for DLR-FLAIR than for acc-FLAIR (p < 0.001); two neuroradiologists attributed significantly higher scores for DLR-FLAIR than for std-FLAIR (p < 0.05). Regarding white matter hyperintensities, all three neuroradiologists significantly preferred DLR-FLAIR (p < 0.0001). DLR-FLAIR exhibited higher similarity to std-FLAIR in terms of visibility of the hyperintensities, with 97% of the hyperintensities rated as nearly identical or equivalent. Quantitatively, DLR-FLAIR demonstrated significantly higher SSIM and regional SSIM values than acc-FLAIR, with significantly lower NRMSE and regional NRMSE values (p < 0.0001)., Conclusions: DLR-FLAIR can reduce scan time and generate images of similar quality to std-FLAIR in patients with white matter hyperintensities. Therefore, DLR-FLAIR may serve as an effective method in traditional magnetic resonance imaging protocols., (© 2024. The Author(s).)

Introduction: This study aimed to evaluate the clinical impact of skeletal muscle mass and nutritional status in gastric cancer patients treated with nivolumab monotherapy as late-line treatment., Methods: We conducted a multi-institutional retrospective study of 90 gastric cancer patients who previously received anti-PD-1 therapy (nivolumab). On computed tomography images captured before nivolumab induction, the skeletal muscle index (SMI, cm2/m2) was defined as the erector muscle area (cm2) divided by the height (m) squared. Patients were divided into two groups: those with SMI-high (n = 45) and those with SMI-low (n = 45). Prognostic nutritional index (PNI) was also calculated before nivolumab induction. The associations of SMI and PNI with response rate (RR), progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety were analyzed., Results: The cutoff values for SMI were determined as 13.45 for males and 10.41 for females. SMI-high was significantly associated with a higher RR (odds ratio = 12.36, p = 0.02) and DCR (odds ratio = 2.97, p = 0.02). Although not significant, PNI-high also tended to be associated with a higher RR. Multivariate analysis showed that SMI-high was independently associated with a higher RR and higher DCR in gastric cancer. Moreover, prognostic analyses revealed that SMI-high (log-rank test p = 0.008) and PNI-high (log-rank test p = 0.0008) were significantly associated with longer OS since nivolumab induction. SMI-high was also associated with longer PFS (log-rank test p = 0.03). There were no significant differences in immune-related adverse event between SMI-low and SMI-high., Conclusion: SMI and PNI were associated with nivolumab efficacy in gastric cancer patients. Management of skeletal muscle loss and nutritional status in gastric cancer patients who will receive nivolumab would be beneficial to enhance survival outcomes., (© 2024 S. Karger AG, Basel.)

A 78-year-old man with a history of pancreatic carcinoma underwent chest computed tomography (CT), which revealed a slowly enlarging consolidation in the right lower lobe. Forceps and percutaneous CT-guided lung biopsies showed no evidence of malignancy; therefore, organizing pneumonia was suspected. However, the patient's serum carbohydrate antigen 19-9 levels increased monthly, raising concerns about malignant lesions. A transbronchial cryobiopsy (TBCB) was performed to confirm the diagnosis of pulmonary metastasis of the pancreatic carcinoma. Pulmonary metastasis is an important differential diagnosis when chest CT shows consolidation, mimicking organized pneumonia. In addition, a TBCB can be a useful diagnostic tool for detecting lepidic growth patterns.