Search

Congenital Disorders of Glycosylation (CDG) are a group of some 200 genetic disorders with PMM2-CDG being the most common disease. These disorders individually remain rare with poorly understood natural history (NH) and causes of mortality. We established a NH study for CDG and collected both prospective and retrospective data on CDG outcomes. In the current data set analysis on deceased patients, we describe the clinical phenotype and causes of death for thirty-seven individuals with various genetic causes of CDG. About a third of this cohort were affected with PMM2-CDG. All of the patients presented with multisystem features with involvement of the neurological system. The majority of patients involved in this study died during the first three years of life, and only four patients lived beyond ten years. The cause of death was unavailable for two patients, and about a third died secondary to cardiopulmonary failure. Progression of neurological involvement, sepsis and respiratory infection were also among the reported causes. Pericardial effusion was the primary cause of death for three infants affected with PMM2-CDG. This study emphasizes the importance of diagnosis and supportive care following the published monitoring and management guidelines for affected patients with CDG to optimize their health and development in the early stages of the disease., Competing Interests: Declaration of competing interest None., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Tailgut cysts (TGCs) are rare congenital lesions located in the retrorectal space, often remaining asymptomatic and incidentally discovered. However, when symptomatic, they can cause significant discomfort and may require surgical intervention. We report a case of a 40-year-old female who presented with persistent and severe coccygeal pain that significantly impaired her quality of life. Imaging studies revealed a cystic mass consistent with a TGC. Conservative management, including pain control and physical therapy, was ineffective, leading to the decision to surgical treatment. The patient underwent successful laparoscopic excision of the cyst, resulting in complete resolution of symptoms without postoperative complications or recurrence. This case underscores the importance of considering TGCs in the differential diagnosis of chronic coccygeal pain and demonstrates that laparoscopic surgery is a safe and effective treatment option when conservative approaches fail., Competing Interests: Human subjects: Consent for treatment and open access publication 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 © 2025, Kitazawa et al.)

Background: The composite physiologic index (CPI) was developed to estimate the extent of interstitial lung disease (ILD) in idiopathic pulmonary fibrosis (IPF) patients based on pulmonary function tests (PFTs). The CALIPER-revised version of the CPI (CALIPER-CPI) was also developed to estimate the volume fraction of ILD measured by CALIPER, an automated quantitative CT postprocessing software. Recently, artificial intelligence-based quantitative CT image analysis software (AIQCT), which can be used to quantify the bronchial volume separately from the ILD volume, was developed and validated in IPF. The aim of this study was to develop AIQCT-derived CPI formulas to quantify CT abnormalities in IPF and to investigate the associations of these CPI formulas with survival., Methods: The first cohort included 116 patients with IPF. In this cohort, ILD, bronchial, and hyperlucent volumes on CT were quantified using AIQCT. New CPI formulas were developed based on PFTs to estimate the volume fraction of ILD (ILD-CPI), the sum of the ILD and bronchial volume fractions (ILDB-CPI), and the sum of the ILD, bronchial and hyperlucent volume fractions (ILDBH-CPI). The associations of the original CPI, the CALIPER-CPI and the AIQCT-derived CPIs with survival were analyzed in the first cohort and in a second cohort of patients with IPF (n = 72)., Results: In the first cohort, over a median observation time of 92.8 months, 79 patients (68.1%) died, and one patient (0.9%) underwent living-donor lung transplantation. The original CPI, the CALIPER-CPI, and all AIQCT-derived CPIs were associated with overall survival (hazard ratios: 1.07-1.22). The C-index of the ILDB-CPI (0.759) was the highest among all AIQCT-derived CPIs and was comparable to that of the original CPI (0.765) and the CALIPER-CPI (0.749). The C-index of the ILDBH-CPI (0.729) was lower than that of the other CPI variables. The second cohort yielded similar C-indices as the first cohort for the original CPI (0.738), CALIPER-CPI (0.757) and ILDB-CPI (0.749)., Conclusions: The ILDB-CPI can predict the outcomes of IPF patients with a similar performance to that of the original CPI and the CALIPER-CPI. Adding the hyperlucent volume to the CPI formula did not improve its predictive accuracy for mortality., Trial Registration: None (no health care interventions were performed)., Competing Interests: Declarations. Ethics approval and consent to participate: The Institutional Review Board of Kyoto University and the Ethics Committee of Tenri Hospital approved this study (approval numbers R1353, E2119 and No. 635, respectively). The requirement for written informed consent was waived due to the retrospective design of this study. This study was conducted in accordance with the amended Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: Michihiro Uyama has no conflicts of interest; Tomohiro Handa received a research grant from FUJIFILM Corporation and Daiichi Sankyo Company, Limited and belongs to an endowed department sponsored by Teijin Pharma Limited; Ryuji Uozumi received personal fees from Daiichi Sankyo, Eisai, Sawai Pharmaceutical, SBI Pharmaceuticals, Statcom and EPS Corporation and lecture fees from Janssen Pharmaceutical and SAS Institute Japan outside the submitted work; Seishu Hashimoto has no conflicts of interest; Yoshio Taguchi has no conflicts of interest; Kohei Ikezoe received a research grant from FUJIFILM Corporation and Daiichi Sankyo Company, Limited; Kiminobu Tanizawa received a research grant from FUJIFILM Corporation and Daiichi Sankyo Company, Limited; Naoya Tanabe received a research grant from FUJIFILM Corporation and Daiichi Sankyo Company, Limited; Tsuyoshi Oguma received a research grant from FUJIFILM Corporation and Daiichi Sankyo Company, Limited; Atsushi Matsunashi has no conflicts of interest; Takafumi Niwamoto has no conflicts of interest; Hiroshi Shima has no conflicts of interest; Ryobu Mori has no conflicts of interest; Tomoki Maetani has no conflicts of interest; Yusuke Shiraishi has no conflicts of interest; Tomomi W. Nobashi has no conflicts of interest; Ryo Sakamoto has no conflicts of interest; Takeshi Kubo has no conflicts of interest; Akihiko Yoshizawa has no conflicts of interest; Kazuhiro Terada has no conflicts of interest; Yuji Nakamoto has no conflicts of interest; and Toyohiro Hirai received a research grant from FUJIFILM Corporation and Daiichi Sankyo Company, Limited., (© 2024. The Author(s).)

A Hoveyda-Grubbs (HG)-type olefin metathesis complex with a selenoether moiety at the terminus of phenoxy moiety was synthesized. The complex showed direct selenium-atom coordination to the ruthenium center, resulting in higher thermodynamic stability compared with the parent HG catalyst. The selenium atom binding enhanced the tolerance to protic solvent molecules in ring-closing metathesis of N -tosyldiallylamide and diethyl diallylmalonate, and also in the cross metathesis between 3-butenylbenzoate and methyl acrylate. The large activation enthalpy observed in the reaction with n -butyl vinyl ether indicated an increased contribution of the "dissociative mechanism" during the initiation of the catalytic cycle. Introducing coordinative atoms or functional groups at the terminal of the phenoxy moiety is a useful strategy to regulate the thermostability of HG-type olefin metathesis catalysts., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Introduction: The extended practice of meditation may reduce the influence of state fatigue by changing neurocognitive processing. However, little is known about the preventive effects of one-session brief focused attention meditation (FAM) on state fatigue in healthy participants or its potential neural mechanisms. This study examined the preventive effects of one-session brief FAM on state fatigue and its neural correlates using resting-state functional MRI (rsfMRI) measurements., Methods: We randomly divided 56 meditation-naïve participants into FAM and control groups. After the first rsfMRI scan, each group performed a 10-minute each condition while wearing a functional near-infrared spectroscopy (fNIRS) device for assessing brain activity. Subsequently, following a second rsfMRI scan, the participants completed a fatigue-inducing task (a Go/NoGo task) for 60 min. We evaluated the temporal changes in the Go/NoGo task performance of participants as an indicator of state fatigue. We then calculated changes in the resting-state functional connectivity (rsFC) of the rsfMRI from before to after each condition and compared them between groups. We also evaluated neural correlates between the changes in rsFC and state fatigue., Results and Discussion: The fNIRS measurements indicated differences in brain activity during each condition between the FAM and control groups, showing decreased medial prefrontal cortex activity and decreased functional connectivity between the medial prefrontal cortex and middle frontal gyrus. The control group exhibited a decrement in Go/NoGo task performance over time, whereas the FAM group did not. These results, thus, suggested that FAM could prevent state fatigue. Compared with the control group, the rsFC analysis revealed a significant increase in the connectivity between the left dorsomedial prefrontal cortex and right superior parietal lobule in the FAM group, suggesting a modification of attention regulation by cognitive effort. In the control group, increased connectivity was observed between the bilateral posterior cingulate cortex and left inferior occipital gyrus, which might be associated with poor attention regulation and reduced higher-order cognitive function. Additionally, the change in the rsFC of the control group was related to state fatigue., Conclusion: Our findings suggested that one session of 10-minute FAM could prevent behavioral state fatigue by employing cognitive effort to modify attention regulation as well as suppressing poor attention regulation and reduced higher-order cognitive function., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Objective: Our report describes clinical, genetic, and biochemical features of participants with a molecularly confirmed congenital disorder of glycosylation (CDG) enrolled in the Frontiers in Congenital Disorders of Glycosylation (FCDGC) Natural History cohort at year 5 of the study., Methods: We enrolled individuals with a known or suspected CDG into the FCDGC Natural History Study, a multicenter prospective and retrospective natural history study of all genetic causes of CDG. We conducted a cross-sectional analysis of baseline study visit data from participants with confirmed CDG who were consented into the FCDGC Natural History Study (5U54NS115198) from October 2019 to November 2023., Results: Three hundred thirty-three subjects consented to the FCDGC Natural History Study. Of these, 280 unique individuals had genetic data available that was consistent with a diagnosis of CDG. These 280 individuals were enrolled into the study between October 8, 2019 and November 29, 2023. One hundred forty-one (50.4%) were female, and 139 (49.6%) were male. Mean and median age at enrollment was 10.1 and 6.5 years, respectively, with a range of 0.22 to 71.4 years. The cohort encompassed individuals with disorders of N-linked protein glycosylation (57%), glycosylphosphatidylinositol anchor disorder (GPI anchor) (15%), disorders of Golgi homeostasis, trafficking and transport (12%), dolichol metabolism disorders (5%), disorders of multiple pathways (6%), and other (5%). The most frequent presenting symptom(s) leading to diagnosis were developmental delay/disability (77%), followed by hypotonia (56%) and feeding difficulties (42%). Mean and median time between first related symptom and diagnosis was 2.7 and 0.8 years, respectively. One hundred percent of individuals in our cohort had developmental differences/disabilities at the time of their baseline visit, followed by 97% with neurologic involvement, 91% with gastrointestinal (GI)/liver involvement, and 88% with musculoskeletal involvement. Severity of disease in individuals was scored on the Nijmegen Progression CDG Rating Scale (NPCRS) with 27% of scores categorized as mild, 44% moderate, and 29% severe. Of the individuals with N-linked protein glycosylation defects, 83% of those with data showed a type 1 pattern on carbohydrate deficient transferrin (CDT) analysis including 82/84 individuals with PMM2-CDG, 6% a type 2 pattern, 1% both type 1 and type 2 pattern and 10% a normal or nonspecific pattern. One hundred percent of individuals with Golgi homeostasis and trafficking defects with data showed a type 2 pattern on CDT analysis, while Golgi transport defect showed a type II pattern 73% of the time, a type 1 pattern for 7%, and 20% had a normal or nonspecific pattern. Most of the variants documented were classified as pathogenic or likely pathogenic using ACMG criteria. For the majority of the variants, the predicted molecular consequence was missense followed by nonsense and splice site, and the majority of the diagnoses are inherited in an autosomal recessive pattern but with disorders of all major nuclear inheritance included., Discussion: The FCDGC Natural History Study serves as an important resource to build future research studies, improve clinical care, and prepare for clinical trial readiness. Herein is the first overview of CDG participants of the FCDGC Natural History Study., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study introduces a dual-catalytic method for cross-dehydrogenative coupling (CDC) between tetrahydroisoquinolines and Py-SF 4 -alkyne using visible-light photoredox catalysis. This protocol enables selective C(sp 3 )-H alkynylation, expanding the synthetic toolkit for SF 4 -based molecules. Demonstrating efficiency and substrate versatility, this approach opens new avenues in hexacoordinated tetrafluorinated sulfur chemistry and CDC strategies and holds significant promise for drug discovery and materials science.

A 74-year-old man with no overt symptoms was referred for a chest computed tomography (CT) that revealed multiple bilaterally pulmonary ground-glass nodules (GGNs) with subtle changes in size over eight months. Surgical lung biopsies were performed in the left upper lobe. A pathologic study confirmed the intravascular large B-cell lymphoma (IVLBCL). This lesion was a nodule-like cluster of atypical cells, meaning that it had been localized for several months. Pulmonary IVLBCL may form focal lesions presenting as GGN on chest CT and progress slowly without apparent symptoms.

Differentiating between idiopathic interstitial pneumonia (IIP) and secondary interstitial pneumonia, particularly connective tissue disease-associated interstitial lung disease (CTD-ILD), can be challenging histopathologically, and there may be discrepancies among pathologists. While surgical lung biopsy has traditionally been considered the gold standard for diagnosing interstitial pneumonia, the usefulness of transbronchial lung cryobiopsy (TBLC) has been reported. If TBLC could effectively distinguish between primary and secondary diseases, it would provide a less invasive option for patients. The aim of this study was to identify specific pathologic findings in TBLC specimens that could assist in distinguishing CTD-ILD from IIP. A total of 93 underwent TBLC at Tenri Hospital between 2018 and 2022. We retrospectively reviewed cases of CTD-ILD exhibiting a nonspecific interstitial pneumonia (NSIP) pattern (CTD-NSIP) and cases of NSIP with an unknown etiology (NSIP-UE), as determined through multidisciplinary discussion. Nineteen patients with CTD-NSIP and 26 patients with NSIP-UE were included in the study for clinicopathological analysis. The CTD-NSIP group had a significantly higher proportion of female patients compared to the NSIP-UE group (79% vs. 31%; p = 0.002). The presence of both fresh and old intraluminal fibrosis within the same TBLC specimen was significantly more frequent in CTD-NSIP group than in the NSIP-UE group (p = 0.023). The presence of an NSIP pattern with co-existing fresh and old intraluminal fibrosis in TBLC specimens raised suspicion for CTD-ILD., 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 Elsevier GmbH. All rights reserved.)

This study investigated the utility of periostin, a matricellular protein, as a prognostic biomarker in patients with idiopathic pulmonary fibrosis (IPF) who received nintedanib. Monomeric and total periostin levels were measured by enzyme-linked immunosorbent assay in 87 eligible patients who participated in a multicenter prospective study. Forty-three antifibrotic drug-naive patients with IPF described in previous studies were set as historical controls. Monomeric and total periostin levels were not significantly associated with the change in forced vital capacity (FVC) or diffusing capacity of the lungs for carbon monoxide (D LCO ) during any follow-up period. Higher monomeric and total periostin levels were independent risk factors for overall survival in the Cox proportional hazard model. In the analysis of nintedanib effectiveness, higher binarized monomeric periostin levels were associated with more favorable suppressive effects on decreased vital capacity (VC) and D LCO in the treatment group compared with historical controls. Higher binarized levels of total periostin were associated with more favorable suppressive effects on decreased D LCO but not VC. In conclusion, higher periostin levels were independently associated with survival and better therapeutic effectiveness in patients with IPF treated with nintedanib. Periostin assessments may contribute to determining therapeutic strategies for patients with IPF., (© 2023. The Author(s).)

Objective Chronic pulmonary aspergillosis (CPA) is an important complication of nontuberculous mycobacterial pulmonary disease (NTM-PD). However, its diagnosis is challenging, as both CPA and NTM-PD present as chronic cavitary disease. The present study evaluated the impact of CPA on the survival of patients with NTM-PD and revealed the key computed tomography findings for a prompt diagnosis. Methods We retrospectively reviewed patients newly diagnosed with NTM-PD in Tenri Hospital (Tenri City, Nara Prefecture, Japan) between January 2009 and March 2018; the patients were followed up until May 2021. Clinical and radiological characteristics were assessed, and patients with CPA were identified. Results A total of 611 patients were diagnosed with NTM-PD. Among them, 38 (6.2%), 102 (17%), and 471 (77%) patients were diagnosed with NTM-PD with CPA, cavitary NTM-PD without CPA, and non-cavitary NTM-PD without CPA, respectively. The 5-year survival rate of the NTM-PD with CPA group (42.8%; 95% confidence interval: 28.7-64.0%) was lower than that of the cavitary NTM-PD without CPA group (74.4%; 95% confidence interval: 65.4-84.6%). A multivariate analysis revealed that fungal balls and cavities with adjacent extrapleural fat were significant predictive factors for NTM-PD with CPA. Conclusion NTM-PD with CPA patients exhibited a worse prognosis than cavitary NTM-PD without CPA patients. Therefore, an unerring diagnosis of CPA is essential for managing patients with NTM-PD. Computed tomography findings, such as fungal balls and cavities with adjacent extrapleural fat, may be valuable diagnostic clues when CPA is suspected in patients with NTM-PD.

Objectives: Pulmonary nontuberculous mycobacterial disease (pNTM) is a common pulmonary complication of rheumatoid arthritis (RA), but their association has rarely been researched. We aimed to reveal the clinical characteristics of RA with pNTM., Methods: Among all the RA patients who visited Tenri hospital from April 2017 to March 2018, we enrolled those fulfilling the 2007 ATS/IDSA diagnostic criteria of pNTM, and sex- and age- matched control group at a ratio of 1:5. Demographic characteristics were compared between the two groups., Results: Among 865 RA patients, 35 (4.0%) patients were complicated with pNTM. RA patients with pNTM had significantly lower BMI and higher rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) positivity. Bronchiectasis was the most frequent lesion, followed by clusters of small nodules, patchy consolidation and cavity. Multivariable logistic regression analysis revealed bronchiectasis as a strong independent associated factor of pNTM. Treatment for pNTM was needed in 14 of the 35 (40%) RA patients with pNTM and sputum negative conversion was accomplished in 11 of the 14 cases (78.6%)., Conclusions: RA patients with lower BMI, RF/ACPA positivity, and bronchiectasis were associated with pNTM. Treatment for pNTM may attain sputum negative conversion and radiological improvement in patients with RA., (© Japan College of Rheumatology 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

While high-level evidence is lacking, numerous retrospective studies have depicted the value of supplemental oxygen in idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases, and its use should be encouraged where necessary. The clinical course and survival of patients with IPF who have been introduced to oxygen therapy is still not fully understood. The objective of this study was to clarify overall survival, factors associated with prognosis, and causes of death in IPF patients after the start of oxygen therapy. This is a prospective cohort multicenter study, enrolling patients with IPF who started oxygen therapy at 19 hospitals with expertise in interstitial lung disease. Baseline clinical data at the start of oxygen therapy and 3-year follow-up data including death and cause of death were assessed. Factors associated with prognosis were analyzed using univariable and multivariable analyses. One hundred forty-seven eligible patients, of whom 86 (59%) were prescribed ambulatory oxygen therapy and 61 (41%) were prescribed long-term oxygen therapy, were recruited. Of them, 111 died (76%) during a median follow-up of 479 days. The median survival from the start of oxygen therapy was 537 ± 74 days. In the univariable analysis, low body mass index (BMI), low forced vital capacity (FVC), low diffusion capacity (D LCO ), resting hypoxemia, short 6 min-walk distance, and high COPD assessment test (CAT) score were significantly associated with poor prognosis. Multivariable analysis revealed low BMI, low FVC, low D LCO , low minimum SpO 2 on 6MWT, and high CAT score were independent factors for poor prognosis. The overall survival of IPF patients after starting oxygen therapy is about 1.5 years. In addition to pulmonary function tests, 6MWT and patient reported outcomes can be used to predict prognosis more accurately.Clinical Trial Registration: UMIN000009322., (© 2023. Springer Nature Limited.)

Background: Bird-related hypersensitivity pneumonitis (BRHP) is an extrinsic allergic alveolitis caused by inhalation of bird antigens. Although the measurement of serum-specific IgG antibodies against budgerigar, pigeon, and parrot with ImmunoCAP® is available in Japan, the utility of the test for patients with causes by bird breeding other than these three species, including contact with wild birds/poultry/bird manure, and use of a duvet is unknown., Methods: Of the 75 BRHP patients who participated in our previous study, 30 were included. Six cases were caused by bird breeding of species other than pigeon, budgerigar, and parrot, seven were in contact with wild birds/poultry/bird manure, and 17 were using a duvet. Bird-specific IgG antibodies were compared among the patients, 64 controls, and 147 healthy participants., Results: In patients with BRHP caused by bird breeding, budgerigar and parrot-specific IgG levels were significantly higher than in disease controls. Only parrot-specific IgG was significantly higher than in disease controls in patients caused by duvet use. However, among patients with acute episodes (acute and recurrent type of chronic BRHP), IgG antibodies against all three species were significantly higher than those of disease controls caused by bird breeding and the use of a duvet., Conclusions: Bird-specific IgG antibody with ImmunoCAP® was useful for screening and diagnosing BRHP caused by other bird species and duvets., Competing Interests: Conflict of Interest Yoshio Taguchi has received honoraria from Nippon Boehringer Ingelheim Co., Ltd.; Yasunari Miyazaki has received honoraria from Nippon Boehringer Ingelheim Co., Ltd.; Tsuyoshi Shirai, Yoshinori Tanino, Takefumi Nikaido, Yotaro Takaku, Seishu Hashimoto, Tomohisa Baba, Takashi Ogura, Kensuke Kataoka, Masayuki Nakayama, Yoshihito Yamada, Sayomi Matsushima, and Keiichiro Minami have no conflicts of interest., (Copyright © 2023 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Eddy current (EC) testing has been selected as a standard candidate for detecting defects in conductive materials in the past few decades. Nevertheless, inventing EC probes capable of detecting minor defects has always been challenging for researchers due to the tradeoff between the probe dimensions and the strength of the EC generated on the surface of the test piece. Here, we use a copper core with a sophisticated design to converge the rotating EC at the tip of the copper core to detect small cracks in all directions in conductive materials. In this method, we can arbitrarily accommodate a large excitation coil so that a larger rotating uniform EC is generated in a small area of the test piece. Hence, the probe can detect cracks in all directions in conductive materials., (© 2023. The Author(s).)

A 45-year-old man with a history of bronchial asthma had fever and elevated eosinophils on the day of surgery for sinusitis, resulting in cancellation of the surgery. Two days later, he was referred to our department for electrocardiographic abnormalities. We suspected eosinophilic myocarditis (EM) since he presented with fever, left ventricular hypokinesis, and hypertrophy on echocardiography, and eosinophilia with elevated cardiac enzymes. We immediately performed an endomyocardial biopsy that showed eosinophilic infiltration of the myocardium. He was diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA) since he suffered from asthma, eosinophilia, sinusitis, and EM. Methylprednisolone pulse therapy followed by oral prednisolone and intravenous cyclophosphamide pulse therapy decreased his eosinophils to within the normal range, and his symptoms subsequently improved. In EGPA, cardiac involvement is less commonly seen compared to other organ involvement. Moreover, patients with EGPA who have cardiac involvement generally have other organ involvement as well. In this report, the patient had only cardiac involvement as organ damage associated with EGPA, except for asthma and sinusitis in the prodromal phase, making it clear that patients with EGPA could present with cardiac involvement alone. Therefore, it is recommended to thoroughly examine for cardiac involvement in patients with suspected EGPA., Learning Objective: We report a case of eosinophilic granulomatosis with polyangiitis (EGPA) presenting with cardiac involvement alone as organ damage, subsequently diagnosed with eosinophilic myocarditis as confirmed by an endomyocardial biopsy. EGPA usually involves other organs in addition to the cardiovascular system; however, patients with EGPA could present with cardiac involvement alone, as in this case. Thus, we should thoroughly investigate for cardiac involvement in patients with suspected EGPA., Competing Interests: None., (© 2023 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Some macroalgae drift on the ocean and are stranded on coasts, and these stranded brown macroalgae are regarded to be degraded by organisms. Alginate is a major component of brown macroalgae. An uncovering of how carbon is cycled through brown macroalgae is needed to deeply understand coastal ecosystems. In this study, to gain insights into metabolism of brown macroalgae and alginate in the organisms, we initially confirmed that supralittoral talitrid amphipods (beach fleas or sandhoppers collected on the Shibagaki coast in Ishikawa Prefecture, Japan) fed on the brown macroalgae. We then isolated bacteria such as Vibrio sp. with alginate-assimilating capability from the gut of the amphipods. Metagenomic analysis of the gut of amphipods housed in several conditions (e.g. macroalgae or paper as feed, non-sterilized or sterilized environment) showed no condition-dependent compositions of bacteria and fungi, but Vibrio sp. were detected at high frequency, in good agreement with the isolation of Vibrio sp. An intervention study using antibiotics showed that amphipods fed on algae or paper at about the same rate in the presence or absence of antibiotics, and that the antibiotics had no effects on the life span. Moreover, intervention with antibiotics completely killed Vibrio sp. and some other bacteria, and had significant effects on the composition of the flora in the gut, with elimination of the variations observed in the guts of amphipods housed without antibiotics. These data suggest that microbes that were killed by antibiotics, including Vibrio sp., in the gut of talitrid amphipods are not essential for assimilation of brown macroalgae., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Nakamura 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.)

Despite the widespread use of email, our knowledge regarding the consequences of email addiction is lacking. The purpose of this study was to develop an email addiction tendency scale to evaluate its correlation to behavior and brain structure. Following this, the validity and reliability of the developed scale was investigated. We used voxel-based morphometry, correlation, and univariate regression analysis to assess the relationships between email addiction tendency scores and regional gray and white matter volumes, depression, and nonverbal reasoning abilities in a large sample of healthy young adults (n = 1152; mean age, 20.69 ± 1.84 years). The content validity ratio, content validity index, principal component analysis, and confirmatory factorial analysis all showed that the email addiction tendency scale (EATS) has high validity. Additionally, the Cronbach's alpha internal consistency and split-half reliability coefficient showed that the EATS has high reliability. We found that email addiction tendency scores were significantly negatively correlated with nonverbal reasoning. We also observed that the email addiction tendency scores were significantly and positively correlated with depression symptom severity and gray matter volume of the left rostrolateral prefrontal cortex (RLPC) in subjects. These results indicate that email addiction tendency is associated with lower mental health outcomes and increased GMV in the left RLPC.

We describe the first case of encephalitis following coronavirus disease 2019 (COVID-19) vaccination. Our patient was a 46-year-old Japanese woman who presented with acute onset diplopia. Subsequent magnetic resonance imaging revealed brain stem encephalitis that was rapidly responsive to high dosage steroid therapy and completely improved. Although the occurrence of encephalitis after vaccination could have just been a casual temporal association, her symptoms were temporally correlated with two vaccinations. Our case suggests caution and indicates treatment and prognosis, despite no evidence of a causal relationship. Nonetheless, this report emphasizes the enormous benefits of vaccination, which should not be undermined., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The detrimental effects of high-level mercury exposure on the central nervous system as well as effects of low-level exposure during early development have been established. However, no previous studies have investigated the effects of mercury level on brain morphometry using advance imaging techniques in young adults. Here, utilizing hair analysis which has been advocated as a method for biological monitoring, data of regional gray matter volume (rGMV), regional white matter volume (rWMV), fractional anisotropy (FA) and mean diffusivity (MD), cognitive functions, and depression among 920 healthy young adults in Japan, we showed that greater hair mercury levels were weakly but significantly associated with diminished cognitive performance, particularly on tasks requiring rapid processing (speed measures), lower depressive tendency, lower rGMV in areas of the thalamus and hippocampus, lower rWMV in widespread areas, greater FA in bilaterally distributed white matter areas overlapping with areas of significant rWMV reductions and lower MD of the widely distributed gray and white matter areas particularly in the bilateral frontal lobe and the right basal ganglia. These results suggest that even normal mercury exposure levels in Japan are weakly associated with differences of brain structures and lower neurobehavioral performance and altered mood among young adults., (© 2022. The Author(s).)

Although loneliness itself is a natural emotion, prolonged loneliness is detrimental to human health. Despite its detrimental effect, few loneliness-related neuroimaging studies have been published and some have limitations on the sample size number. This study aims to find the difference in resting-state functional connectivity associated with loneliness within a big sample size via the seed-based approach. Functional connectivity analysis was performed on a large cohort of young adults (N = 1336) using the seed-based functional connectivity approach to address the concern from previous studies. The analysis yielded statistically significant positive correlations between loneliness and functional connectivities between the inferior frontal gyrus and supplementary motor area, precentral gyrus, and superior parietal lobule. Additionally, the analysis replicated a finding from a previous study, which is increased functional connectivities between the inferior frontal gyrus and supplementary motor area. In conclusion, greater loneliness is reflected by stronger functional connectivity of the visual attention brain area., (© 2022. The Author(s).)

Shame and guilt are distinct negative moral emotions, although they are usually regarded as overlapping affective experiences. Of these two emotions, shame is more closely related to concerns about other people's judgment, whereas guilt is more related to concerns about one's own judgment. Although some studies have tried to identify the psychological process underlying shame as opposed to guilt, there is no clear evidence of brain regions that are specifically relevant to the experience of shame rather than guilt and, more generally, self-blame. We therefore investigated associations between individual differences in shame- and guilt-proneness and the gray and white matter structures of the brain using magnetic resonance imaging and voxel-based morphometry while controlling for associations with guilt- or shame-proneness. To accomplish this goal, we enrolled 590 healthy, right-handed individuals (338 men and 252 women; age, 20.6 ± 1.8 years). We administered a questionnaire to assess shame proneness and guilt proneness. Based on our hypothesis, we found that high shame proneness was associated with decreased regional white matter density only in the right inferior temporal pole, whereas no significant region was associated with guilt. The function of this area may be important for the underlying processes differentiating shame from guilt.

It has been hypothesized that a higher genetic risk of bipolar disorder (BD) is associated with greater creativity. Given the clinical importance of bipolar disorder and the importance of creativity to human society and cultural development, it is essential to reveal their associations and the neural basis of the genetic risk of bipolar disorder to gain insight into its etiology. However, despite the previous demonstration of the associations of polygenic risk score (PRS) of BD and creative jobs, the associations of BD-PRS and creativity measured by the divergent thinking (CMDT) and regional gray matter volume (rGMV) as well as regional white matter volume (rWMV) have not been investigated. Using psychological analyses and whole-brain voxel-by-voxel analyses, we examined these potential associations in 1558 young, typically developing adult students. After adjusting for confounding variables and multiple comparisons, a greater BD-PRS was associated with a greater total CMDT fluency score, and a significant relationship was found in fluency subscores. A greater BD-PRS was also associated with lower total mood disturbance. Neuroimaging analyses revealed that the BD-PRS was associated with greater rGMV in the right inferior frontal gyrus, which is a consistently affected area in BD, as well as a greater rWMV in the left middle frontal gyrus, which has been suggested to play a central role in the increased creativity associated with the risk of BD with creativity. These findings suggest a relationship between the genetic risk of BD and CMDT and prefrontal cortical structures among young educated individuals., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

The structural and functional brain characteristics associated with the excessive use of the internet have attracted substantial research attention in the past decade. In current study, we used voxel-based morphometry (VBM) and multiple regression analysis to assess the relationship between internet addiction tendency (IAT) score and regional gray and white matter volumes (rGMVs and rWMVs) and brain activity during a WM task in a large sample of healthy young adults (n = 1,154, mean age, 20.71 ± 1.78 years). We found a significant positive correlation between IAT score and gray matter volume (GMV) of right supramarginal gyrus (rSMG) and significant negative correlations with white matter volume (WMV) of right temporal lobe (sub-gyral and superior temporal gyrus), right sublobar area (extra-nuclear and lentiform nucleus), right cerebellar anterior lobe, cerebellar tonsil, right frontal lobe (inferior frontal gyrus and sub-gyral areas), and the pons. Also, IAT was significantly and positively correlated with brain activity in the default-mode network (DMN), medial frontal gyrus, medial part of the superior frontal gyrus, and anterior cingulate cortex during a 2-back working memory (WM) task. Moreover, whole-brain analyses of rGMV showed significant effects of interaction between sex and the IAT scores in the area spreading around the left anterior insula and left lentiform. This interaction was moderated by positive correlation in women. These results indicate that IAT is associated with (a) increased GMV in rSMG, which is involved in phonological processing, (b) decreased WMV in areas of frontal, sublobar, and temporal lobes, which are involved in response inhibition, and (c) reduced task-induced deactivation of the DMN, indicative of altered attentional allocation., Competing Interests: The authors declare no competing financial or non-financial interests.

Background: Phase IV clinical trials in Western countries have reported that combined therapy with pirfenidone and nintedanib for idiopathic pulmonary fibrosis (IPF) has a manageable safety profile. However, data on the long-term safety and tolerability of this combination treatment in the real-world setting in Japan are limited., Methods: The retrospective data of 46 patients with IPF who received combination therapy with pirfenidone and nintedanib were obtained from 16 institutes in Japan. Adverse events and adverse drug reactions (ADRs) were reported through a retrospective review of medical records., Results: Nintedanib and pirfenidone were added to preceding treatment with antifibrotic drugs in 32 (69.6%) and 13 (28.3%) patients, respectively. In one patient (2.1%), the two drugs were concurrently initiated. The mean duration of monotherapy before initiating the combination was 26.3 months. In 26 of 38 patients (68.4%), the Gender-Age-Physiology index stage was II or III. Thirty-three patients (71.7%) had some ADRs, and 14 patients (30.4%) permanently discontinued either drug or both drugs owing to the development of ADRs during the observation period (mean: 59 weeks). The percentage of grade III or IV IPF according to the Japanese Respiratory Society severity classification was higher in patients who permanently discontinued either drug or both drugs than in those who continued both drugs (90.9% [10/11; 3 undetermined grade] vs. 61.1% [11/18; 1 undetermined grade]). Decreased appetite (18/46, 39.1%) and diarrhea (16/46, 34.8%) were frequently observed ADRs. Two patients (4.3%) had serious ADRs (liver toxicity and pneumothorax)., Conclusions: Real-world data imply that combination therapy with pirfenidone and nintedanib for IPF has a manageable safety/tolerability profile., Competing Interests: Conflict of Interest Shu Hisata, Kensuke Kataoka, Yoshinobu Saito, and Motoyasu Kato received honoraria from Nippon Boehringer Ingelheim Co., Ltd.; Masashi Bando, Sakae Homma, and Takashi Ogura received honoraria from Nippon Boehringer Ingelheim Co., Ltd. and Shionogi & Co., Ltd.; Yasuhiko Nishioka received honoraria, donations, and research funding from Nippon Boehringer Ingelheim Co., Ltd.; Kazuhiro Yatera received honoraria from Nippon Boehringer Ingelheim Co., Ltd., and donations from Shionogi & Co., Ltd. and Nippon Boehringer Ingelheim Co., Ltd.; Hiroshi Mukae received honoraria, donations, and research funding from Nippon Boehringer Ingelheim Co., Ltd. and Shionogi & Co., Ltd.; Shinyu Izumi, Susumu Sakamoto, Kizuku Watanabe, Yasuo Shimizu, Hiromichi Hara, Yuko Waseda, Yoshinori Tanino, Seishu Hashimoto, and Naohiko Inase have no conflicts of interest to declare., (Copyright © 2021 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Few reports have highlighted the serial changes in pulmonary hypertension during respiratory management. An 18-year-old girl with severe scoliosis was referred to our hospital for worsening dyspnea on exertion. Based on chest X-ray and transthoracic echocardiography findings showing a tricuspid regurgitation pressure gradient (TRPG) of 64 mmHg, the patient was diagnosed with severe alveolar hypoventilation due to thoracic deformity and severe pulmonary hypertension. Her oxygenation improved rapidly under noninvasive positive pressure ventilation, although partial pressure of carbon dioxide remained >80 Torr. Transthoracic echocardiography on day 7 showed clinically significant and rapid improvement of pulmonary hypertension with a TRPG of 30 mmHg.

Objective: Although brain structural studies have demonstrated the neural correlates of neuroticism, the outcomes are not easily identified because of the various possible brain regions involved, low statistical power (low number of subjects), and brain structural measures available, such as mean diffusivity (MD), which are more suitable than standard regional measures of grey and white-matter volume (rGMV, rWMV) and fractional anisotropy (FA). We hypothesized that neuroticism neural correlates could be detected by MD and differentially identified using other measures. We aimed to visualize the neural correlates of neuroticism., Methods: A voxel-by-voxel regression analysis was performed using the MD, rGMV, rWMV, or FA value as the dependent variable and with neuroticism scores based on the NEO-FFI and its confounding factors as independent variables in 1207 (693 men and 514 women; age, 20.7 ± 1.8, 18-27 years), non-clinical students in a cross-sectional study., Results: MD in the cortico- (orbitofrontal cortex, anterior cingulate cortex, and posterior insula) striatal- (caudate and putamen) thalamic loop regions, including the right posterior limb of the internal capsule, were positively associated with neuroticism using the threshold-free cluster enhancement method with a family-wise error-corrected threshold of P < 0.0125 (0.05/4, Bonferroni correction for four types of MRI data [MD, rGMV, rWMV, and FA]) at the whole-brain level., Conclusions: An increased MD has generally been associated with reduced neural tissues and possibly area function. Accordingly, this finding helps elucidate the mechanism of somatization in neuroticism because the regions related to neuroticism are considered neural correlates of somatoform disorders., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Although it is known that health is not merely the absence of disease, the positive aspects of mental health have been less comprehensively researched compared with its negative aspects. Subjective well-being (SWB) is one of the indicators of positive psychology, and high SWB is considered to benefit individuals in multiple ways. However, the neural mechanisms underlying individual differences in SWB remain unclear, particularly in terms of brain microstructural properties as detected by diffusion tensor imaging. The present study aimed to investigate the relationship between measurements of diffusion tensor imaging [mean diffusivity (MD) and fractional anisotropy] and the degree of SWB as measured using a questionnaire. Voxel-based analysis was used to investigate the association between MD and SWB scores in healthy young adults (age, 20.7 ± 1.8 years; 695 males and 514 females). Higher levels of SWB were found to be associated with lower MD in areas surrounding the right putamen, insula, globus pallidus, thalamus and caudate. These results indicated that individual SWB is associated with variability in brain microstructural properties., (© The Author(s) 2021. Published by Oxford University Press.)

Introduction . Kleptomania is an impulse-control disorder that results in an irresistible urge to steal. It is often observed as a comorbidity in patients undergoing pharmacological treatment for Parkinson's disease. Recurrent shopliftings are also observed in the clinical course of frontotemporal dementia. Case Presentation . After successful treatment of severe depression with venlafaxine at a dose of 225 mg/day, a 54-year-old euthymic female patient exhibited recurrent stealing behavior. After the diagnostic exclusion of frontotemporal dementia, kleptomania induced by venlafaxine administration was suspected. The symptoms of kleptomania disappeared with the gradual decrease in the venlafaxine dosage to 37.5 mg/day. Discussion. Venlafaxine is a dual serotonin-norepinephrine reuptake inhibitor. We considered two possible mechanisms to explain the pathophysiology of kleptomania in the present case: (1) increased dopaminergic neural transmission due to the inhibited dopamine reuptake by the norepinephrine transporter with a high dose of venlafaxine or (2) enhanced serotonergic neural transmission by the inhibition of serotonin reuptake by venlafaxine. In past studies, five cases of impulse-control disorder induced by selective serotonin reuptake inhibitors have been reported. This is the fourth report of venlafaxine-induced kleptomania and highlights the importance of considering the possibility of a rare side effect of kleptomania induced by antidepressant., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Kumi Sakurada et al.)

Purpose: The pulmonary function test (PFT) has played an essential role in diagnosing and managing interstitial lung disease (ILD) but has its contraindications and difficult conditions to perform. Therefore, the present study aimed to evaluate dynamic chest radiography (DCR) ability to predict forced vital capacity (FVC) and other PFT parameters of ILD patients., Method: The prospective observational study included 97 patients who underwent DCR at Tenri Hospital (Tenri, Japan) between June 2019 and April 2020. Twenty-five patients with stable disease status underwent DCR twice to evaluate test-retest reliability using the intraclass correlation coefficient. From the lung field areas measured by DCR, lung volumes at maximum inspiration (V.ins) and expiration (V.exp) were estimated. Correlation coefficients between the measured values of DCR and PFT parameters were calculated. Multilinear models for predicting FVC and other PFT parameters were developed., Results: Intraclass correlation coefficients between first and second measurements of V.ins and V.exp were 0.94 (95% CI: 0.89-0.97, p < 0.001) and 0.88 (95% CI: 0.78-0.94, p < 0.001), respectively. The correlation coefficient between V.ins and FVC was 0.86 (95% CI: 0.79-0.90, p < 0.001). A multilinear model for predicting FVC was developed using V.ins, V.exp, age, sex, and body mass index as predictor variables, wherein the adjusted coefficient of determination was 0.814., Conclusions: Lung volumes measured by DCR correlated with the lung function of ILD patients. Prediction models with high predictive power and internal validity were developed, suggesting that DCR can predict FVC and other PFT parameters of ILD patients., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Lead is a toxin known to harm many organs in the body, particularly the central nervous system, across an individual's lifespan. To date, no study has yet investigated the associations between body lead level and the microstructural properties of gray matter areas, and brain activity during attention-demanding tasks. Here, utilizing data of diffusion tensor imaging, functional magnetic resonance imaging and cognitive measures among 920 typically developing young adults, we show greater hair lead levels are weakly but significantly associated with (a) increased working memory-related activity in the right premotor and pre-supplemental motor areas, (b) lower fractional anisotropy (FA) in white matter areas near the internal capsule, (c) lower mean diffusivity (MD) in the dopaminergic system in the left hemisphere and other widespread contingent areas, and (d) greater MD in the white matter area adjacent to the right fusiform gyrus. Higher lead levels were also weakly but significantly associated with lower performance in tests of high-order cognitive functions, such as the psychometric intelligence test, greater impulsivity measures, and higher novelty seeking and extraversion. These findings reflect the weak effect of daily lead level on the excitability and microstructural properties of the brain, particularly in the dopaminergic system., (© 2021. The Author(s).)

Shadowing and reading aloud both involve multiple complex cognitive processes, and both are considered effective methods for second-language learning. The working memory system, particularly the phonological loop, has been suggested to be involved in shadowing and reading aloud. The purpose of this study was to investigate the effects of a 4-week intensive adaptive training including shadowing and reading aloud of second language on working-memory capacity, regional gray matter volume (rGMV), and functional activation related to the n-back working-memory task in young adults. The results showed that compared with the training groups without speaking (listening to compressed speech and active control involving the second language), the training groups with speaking (shadowing and reading aloud) showed a tendency for greater test-retest increases in digit-span scores, and significantly greater test-retest decreases in N-back task reaction time (increase in working memory performance). Imaging analyses revealed compared with the active control group, shadowing group exhibited decreases in rGMV and brain activity during the working memory task (2-back task), in the left cerebellum and reading group exhibited decreases in them in the right anterior insula. These regions are parts of the phonological loop, suggesting the presence of training-induced neural plasticity in these neurocognitive mechanisms., (© 2020. The Author(s).)

Background: Bird antigens are some of the most relevant antigens in hypersensitivity pneumonitis (HP). Possible sources of bird antigens are bird breeding, feather products and fertilizer with fowl droppings. For the screening and diagnosis of HP, the measurement of bird-specific antibodies should be standardized. The aim of this study was to clarify the utility of serum IgG (sIgG) and IgA (sIgA) antibodies to bird antigens in screening and diagnosing acute/chronic bird-related HP with ImmunoCAP® in multi-centre clinical research., Methods: We executed a clinical performance test by conducting a multi-institutional study to measure the levels of sIgG/sIgA against pigeon, parrot and budgerigar antigens by the ImmunoCAP® system in 29 acute and 46 chronic bird-related HP patients., Results: The levels of sIgG/sIgA against the bird antigens of the three species were significantly higher in subjects with acute bird-related HP and chronic bird-related HP with acute episodes (recurrent type) than in the control subjects. For sIgG, the optimal cutoff values by receiver operating characteristic (ROC) analysis were 24.6 mgA/L for pigeon, 14.0 mgA/L for parrot, and 8.7 mgA/L for budgerigar. By measuring multiple bird antigens and combining sIgG values of two species, the sensitivity and specificity for acute and recurrent-type chronic bird-related HP patients were 85-91% and 73-80%, respectively. For recurrent and insidious types of chronic bird-related HP, the sensitivity and specificity were 48-61% and 73-80%, respectively., Conclusions: Measurement of the levels of sIgG/sIgA against pigeon, budgerigar and parrot antigens by ImmunoCAP® was useful for screening and diagnosis in bird-related HP., (Copyright © 2020 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Background: Dipeptidyl peptidase 4 (DPP4) is a serine exopeptidase able to inactivate various oligopeptides, and also a hepatokine. Hepatocyte-specific overexpression of DPP4 is associated with hepatic insulin resistance and liver steatosis., Method: We examined whether weekly DPP4 inhibitor omarigliptin (OMG) can improve liver function as well as levels of inflammation and insulin resistance in type 2 diabetic patients with non-alcoholic fatty liver disease (NAFLD). Further, we investigated the effects of OMG in a diabetic patient with biopsy-confirmed nonalcoholic steatohepatitis (NASH)., Results: In NAFLD patients, OMG significantly decreased levels of aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, homeostatic model assessment of insulin resistance (HOMA-IR), and high-sensitivity C-reactive protein (hsCRP), while no significant change was seen in hemoglobin A1c or body mass index. In the NASH patient, liver function improved markedly, and levels of the hepatic fibrosis marker FIB-4 decreased in parallel with HOMA-IR and hsCRP. Slight but clear improvements in intrahepatic fat deposition and fibrosis appeared to be seen on diagnostic ultrasonography., Conclusion: Weekly administration of the DPP4 inhibitor OMG in ameliorating hepatic insulin resistance may cause beneficial effects in liver with NAFLD/NASH.

Background/Purpose: Psychometric intelligence is closely related to working memory (WM) and the associated brain activity. We aimed to clarify the associations between psychometric intelligence and WM-induced functional connectivity changes. Materials and Methods: Here we determined the associations between psychometric intelligence measured by nonverbal reasoning (using the Raven's Advanced Progressive Matrices) and WM-induced changes in functional connectivity during the N-back paradigm, in a large cohort of 1221 young adults. Results: We observed that the measures of general intelligence showed a significant positive correlation with WM-induced changes in the functional connectivity with the key nodes of the frontoparietal network, such as the bilateral premotor cortices and the presupplementary motor area. Those significant correlations were observed for (1) areas showing a WM-induced increase of the functional connectivity with the abovementioned key nodes, such as the lateral parietal cortex; (2) areas showing a WM-induced decrease of the functional connectivity with the abovementioned key nodes (2-a) such as left perisylvian areas and cuneus, the fusiform gyrus, and the lingual gyrus, which play key roles in language processing, (2-b) hippocampus and parahippocampal gyrus, which play key roles in memory processing, and (2-c) the key node of the default mode network such as the medial prefrontal cortex; as well as (3) the border areas between (1) and (2). Conclusion: Psychometric intelligence is associated with WM-induced changes in functional connectivity, influencing the way in which WM key nodes dynamically modulate the interaction with other brain nodes in response to WM.

Tuberous sclerosis complex 2 (TSC2) is a tumor-suppressor protein that is partially regulated by insulin, energy, oxygen, and growth factors. Mutations in the TSC2 gene and loss of TSC2 promote cell growth by the mammalian target of rapamycin complex 1 (mTORC1) activation. Furthermore, S-adenosylmethionine (SAM) sensor upstream of mTORC1 indirectly inhibits mTORC1 activity via the methionine metabolite SAM. Here, we investigated the effects of methionine on insulin/TSC2/mTORC1 activity. Our results showed that methionine affected TSC2 stability and abolished TSC2 localization to the lysosome. Moreover, activation of insulin signaling contributed to TSC2 degradation in a methionine deprivation-dependent manner. Thus, methionine and insulin crosstalk occurred via TSC2., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The APOE ɛ4 allele is associated with a risk of Alzheimer's disease in the elderly, with the association being pronounced in females. Conversely, findings of the effects of the APOE ɛ4 allele in young adults are mixed. Here, we investigated the sex-genotype interaction effects of the APOE ɛ4 allele on cognitive functions as well as brain structures among 1258 young adults. After adjusting for multiple comparisons, there were significant effects of the interaction between sex and the number of APOE ɛ4 allele on some speed tasks (e.g., simple processing speed tasks and the reverse Stroop task) as well as on regional white matter volume (rWMV). The observed sex-genotype interaction conferred better cognitive performance and greater rWMV in the anterior frontal and precentral white matter areas in females having more APOE ɛ4 alleles and reduced rWMV in the same areas in male having more APOE ɛ4 alleles. These findings support the long-debated antagonistic pleiotropic effects of the APOE ɛ4 allele in females., (© The Author(s) 2020. Published by Oxford University Press.)

Mutations in genes that encode components of tuberous sclerosis complex 2 (TSC2) are associated with tuberous sclerosis complex disease. TSC2 interacts with tuberous sclerosis complex 1 to form a complex that negatively regulates cell growth and proliferation via the inactivation of mechanistic target of rapamycin complex 1. The activity of TSC2 is mainly regulated via posttranslational modifications such as phosphorylation. However, the control of TSC2 activity is not entirely achieved by phosphorylation. In this study, we show that TSC2 is methylated at R1457 and R1459 by protein arginine methyltransferase 1 (PRMT1). Methylation of these two residues can affect the phosphorylation status through protein kinase B (Akt) of TSC2 at T1462 and is essential for TSC2 stability. Taken together, these findings indicate that novel posttranslational modifications are important for the regulation of TSC2 stability through PRMT1-mediated methylation.

Neuropsychology and neuroimaging studies provide distinct views on the key neural underpinnings of social scene understanding (SSU): the amygdala and multimodal neocortical areas such as the posterior superior temporal sulcus (pSTS), respectively. This apparent incongruity may stem from the difference in the assumed cognitive processes of the situation-response association and the integrative or creative processing of social information. To examine the neural correlates of different SSU types using functional magnetic resonance imaging (fMRI), we devised a clothing recommendation task in three types of client's standpoint. Situation-response association was induced by a situation-congruent standpoint (ecological SSU), whereas the integrative and creative processing of social information was elicited by a lack and situation incongruence of the standpoint (perceptual and elaborative SSUs, respectively). Activation characteristic of the ecological SSU was identified in the right amygdala, while that of the perceptual SSU and elaborative SSU demand was identified in the right pSTS and left middle temporal gyrus (MTG), respectively. Thus, the current results provide evidence for the conceptual and neural distinction of the three types of SSU, with basic ecological SSU being supported by a limbic structure while sophisticated integrative or creative SSUs being developed in humans by multimodal association cortices.

The originality of creativity measured by divergent thinking (CMDT) is a unique variable that is positively correlated with psychometric intelligence and other psychological measures. Here, we aimed to determine the associations of CMDT originality/fluency scores and brain activity associated with working memory (WM) and simple cognitive processes during the N-back paradigm in a cohort of 1221 young adults. We observed that originality/fluency scores were associated with greater brain activity during the 0-back simple cognitive task and 2-back WM task in key nodes of the ventral attention system in the right hemisphere. Further, subjects with higher originality/fluency scores showed lower task-induced deactivations in areas of the default mode network, especially during the 2-back task. Psychological analyses revealed the associations of originality/fluency scores with both psychometric intelligence and systemizing. We also observed the effects of interaction between sex and originality/fluency scores on functional activity during the 0-back task in posterior parts of the default mode network together with other areas as well as simple processing speed. These results indicate that the originality of CMDT is associated with (a) greater activation of the ventral attention system, which is involved in reorienting attention and (b) reduced task-induced deactivation of the default mode network, which is indicative of alterations in attentional reallocation, and (c) cognitive correlates of originality of CMDT and revealed sex differences in these associations., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Obesity causes a wide range of systemic diseases and is associated with mood and anxiety disorders. It is also associated with dopaminergic reward system function. However, the relationships between microstructural properties of the dopaminergic system and body mass index (BMI) have not been investigated. In this study, we investigated the associations of BMI with mean diffusivity (MD), diffusion tensor imaging measure in areas of the dopaminergic system (MDDS) in 435 healthy young adults with mild obesity and without obesity (BMI < 40). We detected the association between greater BMI and lower MD of the right globus pallidus and the right putamen. These results suggest that the property of the dopaminergic system is associated with BMI among young adults with mild obesity and without obesity.

Zinc is a biologically essential element and involved in a wide range of cellular processes. Here, we investigated the associations of zinc levels in hair with brain activity during the n-back working memory task using functional magnetic resonance imaging, fractional anisotropy (FA) of diffusion tensor imaging, and cognitive differences in a study cohort of 924 healthy young adults. Our findings showed that greater hair zinc levels were associated with lower brain activity during working memory in extensive areas in the default mode network (i.e., greater task-induced deactivation) as well as greater FA in white matter areas near the hippocampus and posterior limbs of the internal capsule. These findings advance previous non-neuroimaging findings of zinc's associations with excitability, excitability-associated disorders, and myelination.

Numerous studies have reported that the Met allele of the brain-derived neurotrophic factor (BDNF) gene polymorphism reduces neural plasticity. A reduction in mean diffusivity (MD) in diffusion tensor imaging (DTI) characteristically reflects the neural plasticity that involves increased tissue components. In this study, we revealed that the number of Met-BDNF alleles was negatively associated with MD throughout the whole-brain gray and white matter areas of 743 subjects using DTI and whole-brain multiple regression analyses. Within the same sample, the region of interest analysis revealed that the number of Met-BDNF alleles significantly and positively correlated with the mean FA value in the body of the corpus callosum. In addition, we observed interaction effects between BDNF Val66Met polymorphism and daily physical activity levels on MD, but not FA, in significant clusters of the bilateral hemisphere (n = 577 subjects). Post-hoc multiple regression analyses revealed that after correcting for confounding variables, there was a significant negative correlation between the physical activity level and mean MD of the whole brain in the Val/Val group [standardized partial regression coefficient (β) = -0.196, P = 0.005, t = -2.825], but not in the Val/Met (β = 0.050, P = 0.412, t = 0.822) and Met/Met groups (β = 0.092, P = 0.382, t = 0.878). These results underscore the importance of the interaction between physical activity and the BDNF Val66Met polymorphism, which affects the plasticity of neural mechanisms.

In laboratory settings, creativity is measured using tasks of divergent as well as convergent thinking. It has been suggested that brain connectivity is important for creativity. In the present study, we investigated the associations of convergent thinking performance of compound Remote Associates Test (CRAT) with fractional anisotropy (FA) in diffusion tensor imaging and regional white matter (WM) volume (rWMV) in voxel-based morphometry in a large sample of healthy young adults (360 males and 280 females; mean age: 20.9 years, SD ​= ​1.6). We showed that CRAT performance was positively correlated with WM pathway property (i.e., FA) in the left fronto-occipital fasciculus and the left inferior longitudinal fasciculus, which play important roles in processing of language and concept. Further, CRAT performance was negatively correlated with rWMV in the widespread frontal temporal subcortical and cerebellar WM areas, suggesting the unique association of convergent thinking with WM connectivity., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Iron plays a critical role in normal brain functions and development, but it has also been known to have adverse neurological effects., Methods: Here, we investigated the associations of iron levels in hair with regional gray matter volume (rGMV), regional cerebral blood flow (rCBF), fractional anisotropy (FA), mean diffusivity (MD), and cognitive differences in a study cohort of 590 healthy young adults., Results: Our findings showed that high iron levels were associated with lower rGMV in areas including the hippocampus, lower rCBF in the anterior and posterior parts of the brain, greater FA in areas including the part of the splenium of the corpus callosum, lower MD in the overlapping area including the splenium of the corpus callosum, as well as greater MD in the left hippocampus and areas including the frontal lobe., Conclusion: These results are compatible with the notion that iron plays diverse roles in neural mechanisms in healthy young adults., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Background: Empathic concern (EC) is an important interpersonal resilience factor that represents positive adaptation, such as "relating to others" (a factor of posttraumatic growth [PTG]) after disaster. However, controversy exists regarding whether the changes in EC (e.g., the intra-personal change between the acute phase and the disillusionment phase) positively or negatively affect mental health after a disaster. We hypothesized that increased EC may increase chronic fatigue due to over-adjustment (hypothesis 1). We also hypothesized that increasing the changes in "relating to others" could decrease the changes in chronic fatigue (hypothesis 2)., Methods: Forty-nine young, healthy volunteers (M/F: 36/13; age at 3 months after the disaster [3 months]: mean ± SD: 21.1 ± 1.7 years) underwent assessments of EC using the Japanese version of the Interpersonal Reactivity Index, chronic fatigue using the Japanese version of the Checklist Individual Strength (CIS-J) questionnaire, and "relating to others" using the Japanese version of the PTG inventory during the acute phase (3 months) and the disillusionment phase (1 year after the disaster). Pearson product moment correlations at 3 months and 1 year were determined for all scores related to EC. The changes (delta = degree of change from 3 months to 1 year) or scores at 1 year were entered into linear structural equation systems to test the hypotheses., Results: The delta of EC positively affected the delta of the CIS-J, and the delta of relating to others negatively affected the delta of the CIS-J. Both the EC and relating to others scores were negatively associated with the CIS-J score at 1 year. These results were in accordance with hypothesis 1 and 2., Conclusions: We demonstrated the opposite effects of 2 types of ECs, i.e., stability (inherent disposition) and flexibility (degree of change), on the degree of chronic fatigue. Increasing EC with increasing chronic fatigue, but not the change in relating to others, may be a red flag for individuals during the disillusionment phase.

Previous neuroimaging studies have suggested that the neural bases of trait emotional intelligence (TEI) lie in the social cognition network (SCN) and the somatic marker circuitry (SMC). The current study was the first to investigate the associations of total TEI factors and subfactors with mean diffusivity (MD) of these networks as well as regional MD of the dopaminergic system (MDDS). We found that TEI intrapersonal factor score and total TEI score were negatively correlated with regional MDDS in the vicinity of the right putamen and right pallidum and that TEI intrapersonal factor score was negatively correlated with MD values of the fusiform gyrus. Total TEI score and TEI factor scores were positively correlated with MD values of various areas within or adjacent to SCN components, SMC structures and the lateral prefrontal cortex (LPFC). Our MD findings demonstrated the importance of the dopaminergic system to TEI and implicate the SCN, SMC and LPFC in TEI. Future studies are required to investigate the implications of positive and negative associations with MD values., (© The Author(s) 2019. Published by Oxford University Press.)

Guilt, a self-conscious emotion, includes self-focused role taking and also correlates with other-oriented role-taking. Excess guilt proneness might be relevant to obsessive compulsive disorders. The white matter (WM) neural correlates of the degree of guilt have not yet been determined. We hypothesized that the WM structures involved in feelings of guilt are associated with social and moral cognition (inferior parietal lobule [IPL], prefrontal cortex [PFC], and cingulate), and aimed to visualize this using diffusion MRI. We investigated the association between regional WM structures (WM volume, and fractional anisotropy, and mean diffusivity [MD]), and feelings of guilt in 1196 healthy, young students using MRI and the Guilty Feeling Scale, which comprises interpersonal situation (IPS; guilt from hurting friends) and rule-breaking situation (RBS; deontological guilt) scores. The primary novel finding presented here is that MD in the right somatosensory and motor cortices from arm to hand were positively correlated with RBS scores. Further, consistent with our hypothesis, RBS scores were positively correlated with MD in the same regions. These results would be predicted by the Macbeth effect, an obsession with dirt leading to hand-washing rituals resulting from guilt, made famous by the Shakespearian character Lady Macbeth. "What, will these hands ne'er be clean?" William Shakespeare (Shakespeare, 1606) Macbeth.

Background: Botrytis species are well known fungal pathogens of various plants but have not been reported as human pathogens, except as allergenic precipitants of asthma and hypersensitivity pneumonitis., Case Presentation: The asymptomatic patient was referred because of a nodule revealed by chest X-ray. Computed tomography (CT) showed a cavitary nodule in the right upper lobe of the lung. He underwent wedge resection of the nodule, which revealed necrotizing granulomas and a fungus ball containing Y-shaped filamentous fungi, which was confirmed histopathologically. Culture of the specimen yielded white to grayish cotton-like colonies with black sclerotia. We performed multilocus gene sequence analyses including three single-copy nuclear DNA genes encoding glyceraldehyde-3-phosphate dehydrogenase, heat-shock protein 60, and DNA-dependent RNA polymerase subunit II. The analyses revealed that the isolate was most similar to Botrytis elliptica. To date, the pulmonary Botrytis sp. infection has not recurred after lung resection and the patient did not require any additional medication., Conclusions: We report the first case of an immunocompetent patient with pulmonary Botrytis sp. infection, which has not recurred after lung resection without any additional medication. Precise evaluation is necessary for the diagnosis of pulmonary Botrytis infection because it is indistinguishable from other filamentous fungi both radiologically and by histopathology. The etiology and pathophysiology of pulmonary Botrytis infection remains unclear. Further accumulation and analysis of Botrytis cases is warranted.