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Introduction Pregnancy and the postpartum period involve several physiological adaptations crucial for offspring care. Recent research has highlighted reproduction-related brain plasticity in human mothers. Associations with aspects of maternal caregiving suggest adaptive changes that facilitate a woman’s transition to motherhood. However, the dynamic changes that affect a woman’s brain are not merely adaptive, and they likely confer a vulnerability for the mental disorders. To elucidate the pathophysiology of psychiatric problems that occur during the perinatal period, gaining insights into the physiological changes in brain function due to pregnancy is crucial. Objectives Although it has been hypothesized that pregnancy enhances social cognitive functions in mothers to adapt to the offspring care, there are few reports to support this hypothesis. This study aims to investigate whether social cognitive functions change during the first pregnancy, with a focus on maternal adaptation to offspring care. Methods The study included a first pregnancy group and a never-pregnant control group. We conducted a prospective study comparing pregnant women between two-time points (T1, T2); at less than 21 weeks of gestation [T1] and those after 30 weeks of gestation [T2]. To assess the effects of pregnancy and gestational age (< 21 weeks or 30 weeks or more), both the control (never-pregnant) group and pregnant group were evaluated at two time points with similar intervals. The Emotion Recognition Task [ERT] of the Cambridge Neuropsychological Test Automated Battery (CANTAB) was performed to examine the emotion recognition of six basic emotions in facial expressions. We analyzed a cohort of 26 participants in the pregnant group and 25 in the control group. We performed a two-way repeated measures analysis of variance with pregnancy status and gestational period (T1, T2) as independent variables. Results Significant interactions between group and time points (T1, T2) were observed only for Unbiased Hit Rate Anger (p

The East Asian winter monsoon causes orographic snowfall over the windward side of the Japanese islands (facing the Sea of Japan and the northwesterly winter monsoon flow) and negative temperature anomalies around Japan. Daily weather information recorded in old Japanese diaries can provide useful information on the historical occurrences of snowfall days. Here, this information was combined with recently recovered early daily instrumental temperature data collected during the 19th century to reconstruct the occurrence of winter monsoon outbreak days (WMDs) from the 1840s to the early 1850s in Japan. Analyses of interannual and intra-seasonal variations in WMDs revealed active winter monsoon outbreaks in the early 1840s. In 1840/41 and 1841/42, these synchronously occurred with extreme snow events reported in central and southern China. However, winter monsoon outbreaks were absent during the middle to late winters of the mid-1840s and 1853/1854. Freezing records of Lake Suwa in central Japan showed that it did not freeze during 1844/1845 and 1853/1854, which was in agreement with our finding of inactive winter monsoons in these years. Comparing the occurrences of WMDs with early instrumental surface pressure data revealed that WMDs were associated with the active phases of the winter monsoon, as represented by an east–west surface pressure gradient over East Asia.

Introduction Parents have significant genetic and environmental influences, which are known as intergenerational effects, on the cognition, behavior, and brain of their offspring. These intergenerational effects are observed in patients with mood disorders, with a particularly strong association of depression between mothers and daughters. Objectives The main purpose of our study was to investigate female-specific intergenerational transmission patterns in the human brain among patients with depression and their never-depressed offspring. Methods We recruited 78 participants from 34 families, which included remitted parents with a history of depression and their never-depressed biological offspring. We used source-based and surface-based morphometry analyses of magnetic resonance imaging data to examine the degree of associations in brain structure between four types of parent-offspring dyads (i.e. mother-daughter, mother-son, father-daughter, and father-son). Results Using independent component analysis, we found a significant positive correlation of gray matter structure between exclusively the mother-daughter dyads within brain regions located in the default mode and central executive networks, such as the bilateral anterior cingulate cortex, posterior cingulate cortex, precuneus, middle frontal gyrus, middle temporal gyrus, superior parietal lobule, and left angular gyrus. These similar observations were not identified in other three parent-offspring dyads. Conclusions The current study provides biological evidence for greater vulnerability of daughters, but not sons, in developing depression whose mothers have a history of depression. Our findings extend our knowledge on the pathophysiology of major psychiatric conditions that show sex biases and may contribute to the development of novel interventions targeting high-risk individuals. Disclosure of Interest None Declared

Thunderstorm and cloud activities sometimes show a 27-day period, and this has long been studied to uncover a possible important link to solar rotation. Because the 27-day variations in the solar forcing parameters such as solar ultraviolet and galactic cosmic rays become more prominent when the solar activity is high, it is expected that the signal of the 27-day period in meteorological phenomena may wax and wane according to the changes in the solar activity level. In this study, we examine in detail the intensity variations in the signal of the 27-day solar rotational period in thunder and lightning activity from the 18th to the 19th centuries based on 150-year-long records found in old diaries kept in Japan and discuss their relation with the solar activity levels. Such long records enable us to examine the signals of solar rotation at both high and low solar activity levels. We found that the signal of the solar rotational period in the thunder and lightning activity increases as the solar activity increases. In this study, we also discuss the possibility of the impact of the long-term climatological conditions on the signals of the 27-day period in thunder/lightning activities.

Electroconvulsive therapy (ECT) is one of the most effective treatments for depression. ECT induces volume changes in the amygdala, a key center of anxiety. However, the clinical relevance of ECT-induced changes in amygdala volume remains uncertain. We hypothesized that nuclei-specific amygdala volumes and anxiety symptoms in depression could explain the clinical correlates of ECT-induced volume changes. To test this hypothesis, we enrolled patients with depression who underwent ECT (N = 20) in this multicenter observational study and collected MRI data at three time points: before and after treatment and a 6-month follow-up. Patients who received medication (N = 52), cognitive behavioral therapy (N = 63), or transcranial magnetic stimulation (N = 20), and healthy participants (N = 147) were included for comparison. Amygdala nuclei were identified using FreeSurfer and clustered into three subdivisions to enhance reliability and interpretability. Anxiety symptoms were quantified using the anxiety factor scores derived from the Hamilton Depression Rating Scale. Before treatment, basolateral and basomedial subdivisions of the right amygdala were smaller than those of healthy controls. The volumes of the amygdala subdivisions increased after ECT and decreased during the follow-up period, but the volumes at 6-month follow-up were larger than those observed before treatment. These volume changes were specific to ECT. Long-term volume changes in the right basomedial amygdala correlated with improvements in anxiety symptoms. Baseline volumes in the right basolateral amygdala correlated with long-term improvements in anxiety symptoms. These findings demonstrate that clinical correlates of ECT-induced amygdala volume changes are existent, but in a nucleus and symptom-specific manner., Competing Interests: Competing interests: AT is a postdoctoral fellow from Flemish Science Foundation (FWO) (FWO/1283524N). Ethics approval and consent to participate: All methods reported in the current study were performed in accordance with the Ethical Guidelines for Medical and Biological Research Involving Human Subjects. The approval of the current study was obtained from Keio University School of Medicine Ethics Committee [registration number 20190239], Kyoto University Graduate School and Faculty of Medicine Ethics Committee [registration number C0810], National Center of Neurology and Psychiatry Ethics Committee [registration number A2019-098], and Ethics Committee of the Jikei University School of Medicine [registration number 32-160(10241)]. All participants submitted their written informed consent to participate before the recruitment., (© 2024. The Author(s).)

Background: Lung cancer is among the most common types of cancers worldwide, and surgery can be a curative treatment option for this condition. However, some patients experience postoperative recurrence. Hence, predicting early postoperative recurrence to improve patient prognosis is important. This study aimed to determine the usefulness of nutritional inflammation indexes in predicting the prognosis of early recurrence after lung cancer surgery., Methods: A retrospective cohort study was conducted on 310 patients with primary lung cancer who underwent lung lobectomy at Jikei University Hospital from January 1, 2013, to December 31, 2017. The prognostic nutrition index (PNI), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and modified Glasgow prognostic score (mGPS) were calculated. The patients were classified into the high and low groups based on the receiver operating characteristic (ROC) curves. Furthermore, the association between these indexes and postoperative recurrence was analyzed via univariate analysis and using the Kaplan-Meier method., Results: The mean age of the patients was 67.0 years, and the male-to-female ratio was 199:111. The mean observation period was 30.6 months. Patients with a low NLR and mGPS had a significantly longer 5-year recurrence-free survival than those with a high NLR and mGPS (P=0.045 and 0.02, respectively). Patients with a low PNI had a significantly higher 1-year recurrence rate than those with a high PNI (P=0.007)., Conclusions: The PNI is associated with 1-year recurrence, and NLR and mGPS are considerably associated with 5-year postoperative recurrence in patients with lung cancer. Hence, these nutritional inflammatory indices can be useful in predicting postoperative recurrence., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-987/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Figure-eight-shaped nonplanar π-systems adopt distinctive chiral D 2 -symmetric structures, which are ideal for realizing efficient circularly polarized luminescence (CPL). However, the short-step and enantioselective synthesis of figure-eight π-systems represents a considerable challenge for the conventional bottom-up synthetic strategy. Herein, we report that the oxidative cleavage of the internal double bond of a commercially available polycyclic aromatic hydrocarbon, i.e., dibenzo[ g , p ]chrysene (DBC), catalytically affords a figure-eight electron-accepting macrocycle, i.e., cyclobisbiphenylenecarbonyl (CBBC), with high scalability (up to 3.3 g) and excellent enantioselectivity (94% ee). This inner-bond-cleavage approach also applies to larger PAHs, affording highly distorted molecular frameworks that comprise two figure-eight subunits. Furthermore, we demonstrate that the peripheral functionalization of CBBC with carbazole afforded donor-acceptor-type emitter, which shows thermally activated delayed fluorescence and emits CPL with a g value of 1.0 × 10 -2 . This g value is ten times higher than those of previously reported chiral TADF-active emitters for circularly polarized organic light-emitting diodes. These results demonstrate that oxidative inner-bond cleavage is a powerful synthetic strategy for creating innovative materials that incorporate molecules with figure-eight structures.

In February 2004, the Food and Drug Administration (FDA) was the first to approve the combination of cisplatin (CDDP) and pemetrexed (PEM) as standard first-line chemotherapy for untreated, unresectable malignant pleural mesothelioma (MPM). However, after that approval, no progress was made in the standard first-line treatment of MPM for almost 15 years. Positive results from a phase 3 study (Mesothelioma Avastin Cisplatin Pemetrexed Study: MAPS) verifying the effect of bevacizumab, an anti-angiogenesis agent added to CDDP/PEM for unresectable MPM, were published in The Lancet in December 2015; however, this did not lead to approval by national drug regulatory agencies. Furthermore, no second-line treatment was established for cases refractory to CDDP/PEM. In August 2018, the Pharmaceuticals and Medical Devices Agency of Japan was the first in the world to approve monotherapy with nivolumab, an immune checkpoint inhibitor (ICI), for previously unresectable, advanced, or recurrent MPM. Following Japan, in October 2020, the FDA approved the combination of nivolumab and ipilimumab for the treatment of previously untreated, unresectable MPM. In this article, we review the transition of drug treatment for MPM, in light of the historical background, focusing on the benefits of ICIs., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Neuroimaging databases for neuro-psychiatric disorders enable researchers to implement data-driven research approaches by providing access to rich data that can be used to study disease, build and validate machine learning models, and even redefine disease spectra. The importance of sharing large, multi-center, multi-disorder databases has gradually been recognized in order to truly translate brain imaging knowledge into real-world clinical practice. Here, we review MRI databases that share data globally to serve multiple psychiatric or neurological disorders. We found 42 datasets consisting of 23,293 samples from patients with psychiatry and neurological disorders and healthy controls; 1245 samples from mood disorders (major depressive disorder and bipolar disorder), 2015 samples from developmental disorders (autism spectrum disorder, attention-deficit hyperactivity disorder), 675 samples from schizophrenia, 1194 samples from Parkinson's disease, 5865 samples from dementia (including Alzheimer's disease), We recognize that large, multi-center databases should include governance processes that allow data to be shared across national boundaries. Addressing technical and regulatory issues of existing databases can lead to better design and implementation and improve data access for the research community. The current trend toward the development of shareable MRI databases will contribute to a better understanding of the pathophysiology, diagnosis and assessment, and development of early interventions for neuropsychiatric disorders., (© 2024 The Author(s). Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

The glymphatic system, an expansive cerebral waste-disposal network, harbors myriad enigmatic facets necessitating elucidation of their nexus with diverse pathologies. Murine investigations have revealed a relationship between the glymphatic system and affective disorders. This study aimed to illuminate the interplay between bipolar disorder and the glymphatic system. Fifty-eight individuals afflicted with bipolar disorder were identified through meticulous psychiatric assessment. These individuals were juxtaposed with a cohort of 66 comparably aged and sex-matched, mentally stable subjects. Subsequent analysis entailed the application of covariance analysis to evaluate along with the perivascular space (ALPS) index, a novel magnetic resonance imaging method for assessing brain interstitial fluid dynamics via diffusion tensor imaging within the bipolar and control cohorts. We also evaluated the correlation between the ALPS index and clinical parameters, which included the Hamilton Depression scale scores, disease duration, and other clinical assessments. Moreover, partial correlation analyses, incorporating age and sex as covariates, were performed to investigate the relationships between the ALPS index and clinical measures within the two cohorts. A noteworthy adverse correlation was observed between the ALPS index and illness duration. A free-water imaging analysis revealed a substantial elevation in the free-water index within the white-matter tracts, prominently centered on the corpus callosum, within the bipolar cohort relative to that in the control group. In analogous cerebral regions, a conspicuous affirmative correlation was observed between the free-water-corrected radial diffusivity and depression rating scales. Our results showed that the protracted course of bipolar disorder concomitantly exacerbated glymphatic system dysregulation., 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 IBRO. Published by Elsevier Inc. All rights reserved.)

Enteroviruses are single-stranded, positive-sense RNA viruses causing endoplasmic reticulum (ER) stress to induce or modulate downstream signaling pathways known as the unfolded protein responses (UPR). However, viral and host factors involved in the UPR related to viral pathogenesis remain unclear. In the present study, we aimed to identify the major regulator of enterovirus-induced UPR and elucidate the underlying molecular mechanisms. We showed that host Golgi-specific brefeldin A-resistant guanine nucleotide exchange factor 1 (GBF1), which supports enteroviruses replication, was a major regulator of the UPR caused by infection with enteroviruses. In addition, we found that severe UPR was induced by the expression of 3A proteins encoded in human pathogenic enteroviruses, such as enterovirus A71, coxsackievirus B3, poliovirus, and enterovirus D68. The N-terminal-conserved residues of 3A protein interact with the GBF1 and induce UPR through inhibition of ADP-ribosylation factor 1 (ARF1) activation via GBF1 sequestration. Remodeling and expansion of ER and accumulation of ER-resident proteins were observed in cells infected with enteroviruses. Finally, 3A induced apoptosis in cells infected with enteroviruses via activation of the protein kinase RNA-like endoplasmic reticulum kinase (PERK)/C/EBP homologous protein (CHOP) pathway of UPR. Pharmaceutical inhibition of PERK suppressed the cell death caused by infection with enteroviruses, suggesting the UPR pathway is a therapeutic target for treating diseases caused by infection with enteroviruses.IMPORTANCEInfection caused by several plus-stranded RNA viruses leads to dysregulated ER homeostasis in the host cells. The mechanisms underlying the disruption and impairment of ER homeostasis and its significance in pathogenesis upon enteroviral infection remain unclear. Our findings suggested that the 3A protein encoded in human pathogenic enteroviruses disrupts ER homeostasis by interacting with GBF1, a major regulator of UPR. Enterovirus-mediated infections drive ER into pathogenic conditions, where ER-resident proteins are accumulated. Furthermore, in such scenarios, the PERK/CHOP signaling pathway induced by an unresolved imbalance of ER homeostasis essentially drives apoptosis. Therefore, elucidating the mechanisms underlying the virus-induced disruption of ER homeostasis might be a potential target to mitigate the pathogenesis of enteroviruses., Competing Interests: The authors declare no conflict of interest.

Alkyne cycloisomerization of 2,7,10,15-tetra( ortho -alkynylphenyl)benzo[ g , p ]chrysene containing bulky 4-alkoxy-2,6-dimethylphenyl groups at the alkyne terminals selectively proceeded at the sterically crowded bay-region. The obtained double helicene adopts a distorted structure with a high racemization barrier due to the intramolecular steric repulsion.

Human norovirus (HuNoV) is a major cause of acute gastroenteritis and foodborne diseases, affecting all age groups. Despite its clinical needs, no approved antiviral therapies are available. Since the discovery of HuNoV in 1972, studies on anti-norovirals, mechanism of HuNoV infection, viral inactivation, etc., have been hampered by the lack of a robust laboratory-based cultivation system for HuNoV. A recent breakthrough in the development of HuNoV cultivation systems has opened opportunities for researchers to investigate HuNoV biology in the context of de novo HuNoV infections. A tissue stem cell-derived human intestinal organoid/enteroid (HIO) culture system is one of those that supports HuNoV replication reproducibly and, to our knowledge, is most widely distributed to laboratories worldwide to study HuNoV and develop therapeutic strategies. This review summarizes recently developed HuNoV cultivation systems, including HIO, and their use in antiviral studies., Competing Interests: The authors declare no conflict of interest.

Background: The habenula is involved in the pathophysiology of depression. However, its small structure limits the accuracy of segmentation methods, and the findings regarding its volume have been inconsistent. This study aimed to create a highly accurate habenula segmentation model using deep learning, test its generalizability to clinical magnetic resonance imaging, and examine differences between healthy participants and patients with depression., Methods: This multicenter study included 382 participants (patients with depression: N  = 234, women 47.0%; healthy participants: N  = 148, women 37.8%). A 3-dimensional residual U-Net was used to create a habenula segmentation model on 3T magnetic resonance images. The reproducibility and generalizability of the predictive model were tested on various validation cohorts. Thereafter, differences between the habenula volume of healthy participants and that of patients with depression were examined., Results: A Dice coefficient of 86.6% was achieved in the derivation cohort. The test-retest dataset showed a mean absolute percentage error of 6.66, indicating sufficiently high reproducibility. A Dice coefficient of >80% was achieved for datasets with different imaging conditions, such as magnetic field strengths, spatial resolutions, and imaging sequences, by adjusting the threshold. A significant negative correlation with age was observed in the general population, and this correlation was more pronounced in patients with depression ( p < 10 -7 , r  = -0.59). Habenula volume decreased with depression severity in women even when the effects of age and scanner were excluded ( p  = .019, η 2  = 0.099)., Conclusions: Habenula volume could be a pathophysiologically relevant factor and diagnostic and therapeutic marker for depression, particularly in women., (© 2024 The Authors.)

Previous studies have developed and explored magnetic resonance imaging (MRI)-based machine learning models for predicting Alzheimer's disease (AD). However, limited research has focused on models incorporating diverse patient populations. This study aimed to build a clinically useful prediction model for amyloid-beta (Aβ) deposition using source-based morphometry, using a data-driven algorithm based on independent component analyses. Additionally, we assessed how the predictive accuracies varied with the feature combinations. Data from 118 participants clinically diagnosed with various conditions such as AD, mild cognitive impairment, frontotemporal lobar degeneration, corticobasal syndrome, progressive supranuclear palsy, and psychiatric disorders, as well as healthy controls were used for the development of the model. We used structural MR images, cognitive test results, and apolipoprotein E status for feature selection. Three-dimensional T1-weighted images were preprocessed into voxel-based gray matter images and then subjected to source-based morphometry. We used a support vector machine as a classifier. We applied SHapley Additive exPlanations, a game-theoretical approach, to ensure model accountability. The final model that was based on MR-images, cognitive test results, and apolipoprotein E status yielded 89.8% accuracy and a receiver operating characteristic curve of 0.888. The model based on MR-images alone showed 84.7% accuracy. Aβ-positivity was correctly detected in non-AD patients. One of the seven independent components derived from source-based morphometry was considered to represent an AD-related gray matter volume pattern and showed the strongest impact on the model output. Aβ-positivity across neurological and psychiatric disorders was predicted with moderate-to-high accuracy and was associated with a probable AD-related gray matter volume pattern. An MRI-based data-driven machine learning approach can be beneficial as a diagnostic aid., (© 2024. The Author(s).)

Background: Cambodia aims to eliminate all forms of malaria by 2025. In 2020, 90% of all malaria cases were Plasmodium vivax. Thus, preventing P. vivax and relapse malaria is a top priority for elimination. 14-day primaquine, a World Health Organization-recommended radical cure treatment regimen, specifically targets dormant hypnozoites in the liver to prevent relapse. Cambodia introduced P. vivax radical cure with primaquine after glucose-6-phosphate dehydrogenase (G6PD) qualitative testing in 2019. This paper presents Cambodia's radical cure Phase I implementation results and assesses the safety, effectiveness, and feasibility of the programme prior to nationwide scale up., Methods: Phase I implementation was carried out in 88 select health facilities (HFs) across four provinces. Males over 20kgs with confirmed P. vivax or mixed (P. vivax and Plasmodium falciparum) infections were enrolled. A descriptive analysis evaluated the following: successful referral to health facilities, G6PD testing results, and self-reported 14-day treatment adherence. P. vivax incidence was compared before and after radical cure rollout and a controlled interrupted time series analysis compared the estimated relapse rate between implementation and non-implementation provinces before and after radical cure., Results: In the 4 provinces from November 2019 to December 2020, 3,239 P. vivax/mixed infections were reported, 1,282 patients underwent G6PD deficiency testing, and 959 patients received radical cure, achieving 29.6% radical cure coverage among all P. vivax/mixed cases and 98.8% coverage among G6PD normal patients. Among those who initiated radical cure, 747 patients (78%) completed treatment. Six patients reported side effects. In implementation provinces, an average 31.8 relapse cases per month were estimated signaling a 90% (286 cases) reduction in relapse compared to what would be expected if radical cure was not implemented., Conclusions: Plasmodium vivax radical cure is a crucial tool for malaria elimination in Cambodia. The high coverage of radical cure initiation and adherence among G6PD normal patients demonstrated the high feasibility of providing radical cure at point of care in Cambodia. Incomplete referral from community to HFs and limited capacity of HF staff to conduct G6PD testing in high burden areas led to lower coverage of G6PD testing. Phase I implementation informed approaches to improve referral completion and patient adherence during the nationwide expansion of radical cure in 2021., (© 2024. The Author(s).)

We investigated the chemical and physical properties of internally functionalized dibenzo[ g,p ]chrysene (DBC) derivatives. These molecules exhibit chiral double-helicene-like structures that are configurationally stable at ambient temperatures. The internal substituents control the conformational change in the excited state, thereby modulating the emission intensity. Notably, the DBC derivative with a methylenedioxy unit undergoes aromatization through elimination of the internal substituent upon photoexcitation, resulting in the formation of DBC.

Visual illusions provide valuable insights into the brain's interpretation of the world given sensory inputs. However, the precise manner in which brain activity translates into illusory experiences remains largely unknown. Here, we leverage a brain decoding technique combined with deep neural network (DNN) representations to reconstruct illusory percepts as images from brain activity. The reconstruction model was trained on natural images to establish a link between brain activity and perceptual features and then tested on two types of illusions: illusory lines and neon color spreading. Reconstructions revealed lines and colors consistent with illusory experiences, which varied across the source visual cortical areas. This framework offers a way to materialize subjective experiences, shedding light on the brain's internal representations of the world.

It is essential to employ efficient measures to prevent the transmission of pathogenic agents during a pandemic. One such method involves using hypochlorous acid (HClO) solution. The oxidative properties of HClO water (HAW) can contribute to its ability to eliminate viral particles. Here, we examined a highly purified slightly acidic hypochlorous acid water (Hp-SA-HAW) obtained from the reverse osmosis membrane treatment of an electrolytically-generated SA-HAW for its anti-viral activity and mode of action on viral proteins. Hp-SA-HAW exhibited broad-spectrum antiviral effects against various viruses, including adenovirus, hepatitis B virus, Japanese encephalitis virus (JEV), and rotavirus. Additionally, Hp-SA-HAW treatment dose-dependently resulted in irreversibly aggregated multimers of the JEV envelope and capsid proteins. However, Hp-SA-HAW treatment had no discernible effect on viral RNA, indicating that Hp-SA-HAW acts against amino acids rather than nucleic acids. Furthermore, Hp-SA-HAW substantially reduced the infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including the ancestral variant and other multiple variants. Hp-SA-HAW treatment induced the aggregation of the SARS-CoV-2 spike and nuclear proteins and disrupted the binding of the purified spike protein of SARS-CoV-2 to human ACE2. This study demonstrates that the broad-spectrum virucidal activity of highly purified HClO is attributed to viral protein aggregation of virion via protein oxidation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer TH declared a shared affiliation with the authors TH, SK, and KM to the handling editor at the time of review., (Copyright © 2023 Dianty, Hirano, Anzai, Kanai, Hayashi, Morimoto, Kataoka-Nakamura, Kobayashi, Uemura, Ono, Watanabe, Kobayashi, Murakami, Kikuchi, Hotta, Yoshikawa, Taguwa and Matsuura.)

Background: Maintaining remission after electroconvulsive therapy (ECT) is clinically relevant in patients with depression, and maintenance ECT has been introduced in patients who fail to maintain remission after ECT. However, the clinical characteristics and biological background of patients who receive maintenance ECT are poorly understood. Thus, this study aimed to examine the clinical background of patients who underwent maintenance ECT., Methods: Patients with major depressive disorder who underwent ECT followed by maintenance ECT (mECT group) and those who did not (acute ECT [aECT] group) were included. Clinical characteristics, including the results of neuroimaging examinations for Parkinson's disease (PD) and dementia with Levy body (DLB) such as myocardial 123I-metaiodobenzylguanidine (MIBG) scintigraphy and dopamine transporter imaging single-photon emission computerized tomography (DaT-SPECT), were compared between the groups., Results: In total, 13 and 146 patients were included in the mECT and aECT groups, respectively. Compared to the aECT group, the mECT group showed a significantly higher prevalence of melancholic features (92.3% vs. 27.4%, p < 0.001) and catatonic features (46.2% vs. 9.6%, p = 0.002). Overall, 8 of the 13 patients in the mECT group and 22 of the 146 patients in the aECT group underwent neuroimaging examinations for PD/DLB. The rate of patients examined is significantly higher in the mECT group than in the aECT group (61.5% vs. 11.2%, p < 0.001). Among the groups examined, 7/8 patients in the mECT group and 16/22 patients in the aECT group showed relevant neuroimaging findings for PD/DLB; the positive rate was not significantly different between the two groups (87.5% vs. 72.7%, p = 0.638)., Conclusions: Patients who receive acute and maintenance ECT may have underlying neurodegenerative diseases, including PD/DLB. Investigating the neurobiology of patients who receive maintenance ECT is important for developing appropriate treatments for depression., (© 2023. The Author(s).)

Introduction: Few biomarkers can be used clinically to diagnose and assess the severity of depression. However, a decrease in activity and sleep efficiency can be observed in depressed patients, and recent technological developments have made it possible to measure these changes. In addition, physiological changes, such as heart rate variability, can be used to distinguish depressed patients from normal persons; these parameters can be used to improve diagnostic accuracy. The proposed research will explore and construct machine learning models capable of detecting depressive episodes and assessing their severity using data collected from wristband-type wearable devices., Methods and Analysis: Patients with depressive symptoms and healthy subjects will wear a wristband-type wearable device for 7 days; data on triaxial acceleration, pulse rate, skin temperature, and ultraviolet light will be collected. On the seventh day of wearing, the severity of depressive episodes will be assessed using Structured Clinical Interview for DSM-5 (SCID-5), Hamilton Depression Rating Scale (HAMD), and other scales. Data for up to five 7-day periods of device wearing will be collected from each subject. Using wearable device data associated with clinical symptoms as supervisory data, we will explore and build a machine learning model capable of identifying the presence or absence of depressive episodes and predicting the HAMD scores for an unknown data set., Discussion: Our machine learning model could improve the clinical diagnosis and management of depression through the use of a wearable medical device., Clinical Trial Registration: [https://jrct.niph.go.jp/latest-detail/jRCT1031210478], identifier [jRCT1031210478]., Competing Interests: TaK was the president of i2medical LLC and has received consultant fees from Otsuka, Pfizer, and Sumitomo and speaking fee from Banyu, Eli Lilly, Sumitomo, Janssen, Novartis, Otsuka, and Pfizer. TH was a board member of i2medical LLC and had received consulting fees from FRONTEO Inc. YTa, K-cL, and NK were a board member of i2medical LLC. YO, HI, YM, and YTs were employed by Sumitomo Pharma Co., Ltd. GM has received speaking fees from Janssen, Meiji Seika Pharma, Otsuka, and Yoshitomi Yakuhin. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kishimoto, Kinoshita, Kikuchi, Bun, Kitazawa, Horigome, Tazawa, Takamiya, Hirano, Mimura, Liang, Koga, Ochiai, Ito, Miyamae, Tsujimoto, Sakuma, Kida, Miura, Kawade, Goto and Yoshino.)

Objectives: This study examined whether a resected lung lobe can affect the accuracy of postoperative forced expiratory volume in 1 s (FEV1) predicted using the subsegment counting method and three-dimensional computed tomography (3D-CT) volumetry., Methods: Overall, 125 patients who underwent lobectomy through video-assisted thoracic surgery were enrolled in this retrospective study. Pulmonary function tests were performed preoperatively and postoperatively at 3 months. We defined the accuracy index as the ratio of predicted postoperative FEV1 to measured postoperative FEV1 and compared the accuracy index of the subsegment counting method and 3D-CT volumetry. Factors affecting the accuracy index were also examined., Results: The accuracy index of the subsegment counting method was 0.94 ± 0.12, versus 0.93 ± 0.11 for 3D-CT volumetry (P = 0.539). There was a significant difference among the resected lobes in the accuracy index of the subsegment counting method (P < 0.001) but not in that of 3D-CT volumetry (P = 0.370). The resected lobe, the number of staples used for interlobar dissection and interstitial pneumonia were significantly associated with the accuracy index of the subsegment counting method (all P < 0.001). The number of staples and interstitial pneumonia were significantly associated with the accuracy index of 3D-CT volumetry (P < 0.001, respectively), whereas the resected lobe was not a significant factor (P = 0.240)., Conclusions: The resected lobe affected the accuracy of the subsegment counting method but not that of 3D-CT volumetry. Furthermore, 3D-CT volumetry predicted postoperative FEV1 independent of the resected lobe., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Aim: Parents have significant genetic and environmental influences, which are known as intergenerational effects, on the cognition, behavior, and brain of their offspring. These intergenerational effects are observed in patients with mood disorders, with a particularly strong association of depression between mothers and daughters. The main purpose of our study was to investigate female-specific intergenerational transmission patterns in the human brain among patients with depression and their never-depressed offspring., Methods: We recruited 78 participants from 34 families, which included remitted parents with a history of depression and their never-depressed biological offspring. We used source-based and surface-based morphometry analyses of magnetic resonance imaging data to examine the degree of associations in brain structure between four types of parent-offspring dyads (i.e. mother-daughter, mother-son, father-daughter, and father-son)., Results: Using independent component analysis, we found a significant positive correlation of gray matter structure between exclusively the mother-daughter dyads within brain regions located in the default mode and central executive networks, such as the bilateral anterior cingulate cortex, posterior cingulate cortex, precuneus, middle frontal gyrus, middle temporal gyrus, superior parietal lobule, and left angular gyrus. These similar observations were not identified in other three parent-offspring dyads., Conclusions: The current study provides biological evidence for greater vulnerability of daughters, but not sons, in developing depression whose mothers have a history of depression. Our findings extend our knowledge on the pathophysiology of major psychiatric conditions that show sex biases and may contribute to the development of novel interventions targeting high-risk individuals., (© 2022 The Authors. Psychiatry and Clinical Neurosciences © 2022 Japanese Society of Psychiatry and Neurology.)

Objectives: Weight assessment is an easy-to-understand method of health checkup. The present study investigated the association between weight loss (WL) after lung cancer (LC) surgery and short-mid-term prognosis., Methods: The data of patients who underwent radical lobectomy for primary LC were assessed between December 2017 and June 2021. Percentage weight gain or loss was determined at 3, 6 and 12 months postoperatively based on preoperative weight. The timing of decreased weight was divided into 0-3, 3-6 and 6-12 months. We also evaluated the relationship between severe WL (SWL) and prognosis., Results: We reviewed 269 patients, of whom 187 (69.5%) showed WL within 1 year after surgery. The interquartile range for maximal WL was 2.0-8.2% (median 4.0%). Furthermore, we defined SWL as WL ≥8%. Twenty-five patients (9.3%) died: 9 from primary LC and 16 from non-LC causes. Cancer recurrences occurred in 45 patients (16.7%). WL occurred from 6 to 12 months postoperatively was associated with poor overall survival and recurrence-free survival (P &lt; 0.05, both). Body mass index &lt;18.5 kg/m2 and idiopathic pulmonary fibrosis were predictive factors (P &lt; 0.05, all). In the SWL group, overall survival, recurrence-free survival and non-cancer-specific were worse (P = 0.001, 0.005 and 0.019, respectively). Age ≥70 years and severe postoperative complications were predictive factors for SWL (P &lt; 0.05, all)., Conclusions: WL from 6 to 12 months postoperatively and SWL were associated with poor prognosis. Ongoing nutritional management is important to prevent life-threatening WL in patients with predictive factors., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Aim: Healthy older drivers may be at high risk of fatal traffic accidents. Our recent study showed that volumetric alterations in gray matter in the brain regions within the dorsal attention network (DAN) were strongly related to the risk of unsafe driving in healthy older people. However, the relationship between white matter (WM) structural connectivity and driving ability in healthy older people is still unclear., Methods: We used diffusion tensor imaging to examine the association between microstructural alterations in the DAN and the risk of unsafe driving among healthy older people. We enrolled 32 healthy older individuals aged over 65 years and screened unsafe drivers using an on-road driving test. We then determined the pattern of WM aberrations in unsafe drivers using tract-based spatial statistics., Results: The analysis demonstrated that unsafe drivers had significantly higher axial diffusivity values in nine WM clusters compared with safe drivers. These results were primarily observed bilaterally in the dorsal superior longitudinal fasciculus, which is involved in the DAN. Furthermore, correlation analyses showed that higher axial diffusivity values in the superior longitudinal fasciculus were associated with lower Trail Making Test A scores within unsafe drivers. This result suggests that functionally, WM microstructural alterations in the DAN are associated with attention problems, which may contribute to the risk of unsafe driving among healthy older people., Conclusion: Our findings may elucidate the neurobiological mechanisms underlying the increased risk of unsafe driving in healthy older people, potentially facilitating the development of new interventions to prevent fatal accidents., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Psychiatry and Clinical Neurosciences Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Objective: Previous prediction models for electroconvulsive therapy (ECT) responses have predominantly been based on neuroimaging data, which has precluded widespread application for severe cases in real-world clinical settings. The aims of this study were (1) to build a clinically useful prediction model for ECT remission based solely on clinical information and (2) to identify influential features in the prediction model., Methods: We conducted a retrospective chart review to collect data (registered between April 2012 and March 2019) from individuals with depression (unipolar major depressive disorder or bipolar disorder) diagnosed via DSM-IV-TR criteria who received ECT at Keio University Hospital. Clinical characteristics were used as candidate features. A light gradient boosting machine was used for prediction, and 5-fold cross-validation was performed to validate our prediction model., Results: In total, 177 patients with depression underwent ECT during the study period. The remission rate was 63%. Our model predicted individual patient outcomes with 71% accuracy (sensitivity, 86%; specificity, 46%). A shorter duration of the current episodes, lower baseline severity, higher dose of antidepressant medications before ECT, and lower body mass index were identified as important features for predicting remission following ECT., Conclusions: We developed a prediction model for ECT remission based solely on clinical information. Our prediction model demonstrated accuracy comparable to that in previous reports. Our model suggests that introducing ECT earlier in the treatment course may contribute to improvements in clinical outcomes., (© Copyright 2022 Physicians Postgraduate Press, Inc.)

The three-dimensional conformation of RNA is important in the function and fate of the molecule. The common conformation of mRNA is formed based on the closed-loop structure and internal base pairings with the activity of the ribosome movements. However, recent reports suggest that the closed-loop structure might not be formed in many mRNAs. This implies that mRNA can be considered as a single polymer in the cell. Here, we introduce the Three-dimensional RNA Illustration Program (TRIP) to model the three-dimensional RNA folding shape based on single-chain models and angle restriction of each bead component from previously reported single-molecule fluorescence in situ hybridization (smFISH) experimental data. This simulation method was able to recapitulate the mRNA conformation change of the translation activity and three-dimensional positional interaction between an organelle and its localized mRNAs as end-to-end distances. Within the analyzed cases, base-pairing interactions only have minor effects on the three-dimensional mRNA conformation, and instead single-chain polymer characteristics have a more significant impact on the conformation. This top-down method will be used to interpret the aggregation mechanism of mRNA under different cellular conditions such as nucleolus and phase-separated granules., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)

Objective: Although anesthetics play an important role in electroconvulsive therapy (ECT), the clinical efficacy and seizure adequacy of sevoflurane in the course of ECT remain unclear. The purpose of this study was to examine the clinical efficacy and seizure adequacy of sevoflurane, compared with those of thiopental, in the course of ECT in patients with mood disorders., Methods: We conducted a retrospective chart review. Patients who underwent a course of ECT and received sevoflurane ( n = 26) or thiopental ( n = 26) were included. Factors associated with ECT and treatment outcomes were compared between the two groups using propensity score (PS) matching. Between-group differences were examined using an independent t -test for continuous variables and a χ 2 -test for categorical variables., Results: Patients who received sevoflurane needed more stimulations (sevoflurane: 13.2 ± 4 times, thiopental: 10.0 ± 2.5 times, df = 51, p = 0.001) and sessions (sevoflurane: 10.0 ± 2.1 times, thiopental: 8.4 ± 2.1 times, df = 51, p = 0.01) and had more inadequate seizures (sevoflurane: 5 ± 3.9 times, thiopental: 2.7 ± 2.7 times, df = 51, p = 0.015). Remission and response rates were similar in both groups., Conclusion: The present findings indicate that sevoflurane should be used with caution in ECT and only when the clinical rationale is clear., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yatomi, Uchida, Takamiya, Wada, Kudo, Nakajima, Nishida, Yamagata, Mimura and Hirano.)

Enteric viruses, including numerous viruses that initiate infection in enteric canal, are recognized as important agents that cause wide spectrum of illnesses in humans, depending on the virus type. They are mainly transmitted by fecal-oral route with several vector such as contaminated water or food. Infections by enteric viruses, such as noroviruses and rotaviruses, frequently cause widespread acute gastroenteritis, leading to significant health and economic burdens and therefore remain a public health concern. Like other viruses, enteric viruses ''hijack'' certain host factors (so called pro-viral factors) for replication in infected cells, while escaping the host defense system by antagonizing host anti-viral factors. Identification(s) of these factors is needed to better understand the molecular mechanisms underlying viral replication and pathogenicity, which will aid the development of efficient antiviral strategies. Recently, the advancement of genome-editing technology, especially the clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 system, has precipitated numerous breakthroughs across the field of virology, including enteric virus research. For instance, unbiased genome-wide screening employing the CRISPR-Cas9 system has successfully identified a number of previously unrecognized host factors associated with infection by clinically relevant enteric viruses. In this review, we briefly introduce the common techniques of the CRISPR-Cas9 system applied to virological studies and discuss the major findings using this system for studying enteric virus infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hirano, Murakami and Hayashi.)

Human noroviruses (HuNoVs) are acute viral gastroenteritis pathogens that affect all age groups, yet no approved vaccines and drugs to treat HuNoV infection are available. In this study, we screened an antiviral compound library to identify compound(s) showing anti-HuNoV activity using a human intestinal enteroid (HIE) culture system in which HuNoVs are able to replicate reproducibly. Dasabuvir (DSB), which has been developed as an anti-hepatitis C virus agent, was found to inhibit HuNoV infection in HIEs at micromolar concentrations. Dasabuvir also inhibited severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human rotavirus A (RVA) infection in HIEs. To our knowledge, this is the first study to screen an antiviral compound library for HuNoV using HIEs, and we successfully identified dasabuvir as a novel anti-HuNoV inhibitor that warrants further investigation. IMPORTANCE Although there is an urgent need to develop effective antiviral therapy directed against HuNoV infection, compound screening to identify anti-HuNoV drug candidates has not been reported so far. Using a human HIE culture system, our compound screening successfully identified dasabuvir as a novel anti-HuNoV inhibitor. Dasabuvir's inhibitory effect was also demonstrated in the cases of SARS-CoV-2 and RVA infection, highlighting the usefulness of the HIE platform for screening antiviral agents against various viruses that target the intestines.

Multichannel near-infrared spectroscopy (NIRS), including 52-channel NIRS (52ch-NIRS), has been used increasingly to capture hemodynamic changes in the brain because of its safety, low cost, portability, and high temporal resolution. However, optode caps might cause pain and motion artifacts if worn for extended periods of time because of the weight of the cables and the pressure of the optodes on the scalp. Recently, a small NIRS apparatus called compact NIRS (cNIRS) has been developed, and uses only a few flexible sensors. Because this device is expected to be more suitable than 52ch-NIRS in the clinical practice for patients with children or psychiatric conditions, we tested whether the two systems were clinically comparable. Specifically, we evaluated the correlation between patterns of hemodynamic changes generated by 52ch-NIRS and cNIRS in the frontopolar region. We scanned 14 healthy adults with 52ch-NIRS and cNIRS, and measured activation patterns of oxygenated-hemoglobin [oxy-Hb] and deoxygenated-hemoglobin [deoxy-Hb] in the frontal pole while they performed a verbal fluency task. We performed detailed temporal domain comparisons of time-course patterns between the two NIRS-based signals. We found that 52ch-NIRS and cNIRS showed significant correlations in [oxy-Hb] and [deoxy-Hb] time-course changes in numerous channels. Our findings indicate that cNIRS and 52ch-NIRS capture similar task-dependent hemodynamic changes due to metabolic demand, which supports the validity of cNIRS measurement techniques. Therefore, this small device has a strong potential for clinical application with infants and children, as well as for use in the rehabilitation or treatment of patients with psychiatric disorders using biofeedback., Competing Interests: MM has a potential conflict of interest; for the present study, BrainEnergy Inc. provided a project grant and material support [temporary rental of cNIRS (BrainEnergy System)]. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hirano, Takamiya, Yamamoto, Minami, Mimura and Yamagata.)

Background: Electroconvulsive therapy (ECT) is the most effective antidepressant treatment for severe depression. Although recent structural magnetic resonance imaging (MRI) studies have consistently reported ECT-induced hippocampal volume increases, most studies did not find the association of the hippocampal volume changes with clinical improvement. To understand the underlying mechanisms of ECT action, we aimed to identify the longitudinal effects of ECT on hippocampal functional connectivity (FC) and their associations with clinical improvement., Methods: Resting-state functional MRI was acquired before and after bilateral ECT in 27 depressed individuals. A priori hippocampal seed-based FC analysis and a data-driven multivoxel pattern analysis (MVPA) were conducted to investigate FC changes associated with clinical improvement. The statistical threshold was set at cluster-level false discovery rate-corrected p < 0.05., Results: Depressive symptom improvement after ECT was positively associated with the change in the right hippocampus-ventromedial prefrontal cortex FC, and negatively associated with the right hippocampus-superior frontal gyrus FC. MVPA confirmed the results of hippocampal seed-based analyses and identified the following additional clusters associated with clinical improvement following ECT: the thalamus, the sensorimotor cortex, and the precuneus., Conclusions: ECT-induced change in the right frontotemporal connectivity and thalamocortical connectivity, and changes in the nodes of the default mode network were associated with clinical improvement. Modulation of these networks may explain the underlying mechanisms by which ECT exert its potent and rapid antidepressant effect.

Objective: Although the value of video-assisted thoracic surgery for acute pyothorax is becoming widely recognized, the optimal timing of surgery has not been established. Therefore, we aimed to determine the optimal timing of video-assisted thoracic surgery in acute pyothorax., Methods: We retrospectively reviewed 38 consecutive video-assisted thoracic surgeries performed for acute pyothorax between January 2013 and December 2017 at our institution. Data were analyzed using the independent samples t test and Mann-Whitney U test. A receiver-operating characteristic curve was used to identify the optimal time for intervention., Results: The average time from disease onset to surgery was 17.9 days, and the average preoperative drainage period was 8.3 days. The operation was completed in all patients with video-assisted thoracic surgery curettage and drainage under general anesthesia; single lung ventilation was administered, and one or two thoracic drains were placed. The average postoperative drainage period was 10.8 days. Intraoperative complications were observed in two cases; no perioperative death occurred. Additional surgery was performed in four cases because of poor treatment response. There was no recurrence of pyothorax over a mean postoperative follow-up period of 42.5 months. A receiver-operating characteristic curve showed that the cut-off time from disease onset to surgery was 21.0 days; complication rates were 14.3% and 25.0% for patients operated on before and after 21 days, respectively., Conclusions: Thoracoscopic surgery for acute pyothorax is safe and curative, and should be performed within 21 days of disease onset to avoid postoperative complications., (© 2021. The Japanese Association for Thoracic Surgery.)

Background: Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms with malignant potential. No effective treatment other than surgical resection has been established for lung metastases of PEComas. We describe a patient who underwent complete surgical resection via bilateral lobectomy involving a two-step procedure for lung metastases 8 years after undergoing radical surgery for a colonic PEComa., Case Presentation: A 53-year-old woman underwent partial colectomy for a PEComa in the transverse colon 8 years ago. She presented with an abnormal chest shadow during a health examination. Chest computed tomography (CT) revealed a solid nodule 2 cm in diameter located centrally in the right lower lobe and a solid nodule 3 cm in diameter located centrally in the left upper lobe. Positron emission tomography revealed 18F-fluorodeoxyglucose uptake in these nodules. These nodules were suspected to be metastatic tumors of the colonic PEComa and were considered for complete surgical resection. Segmentectomy could not be performed because of the anatomical location of the tumors straddling the segments; therefore, bilateral lobectomy was required for complete surgical resection. Therefore, we performed two-step lobectomy safely with the expectation of pulmonary function recovery. Microscopically, the tumors were diagnosed as lung metastases of the PEComa. One year after the last surgery, no recurrence was detected, and the patient's pulmonary function improved., Conclusions: This case indicates that even if multiple lung metastases of a PEComa require bilateral lobectomy, complete resection with a two-step surgery may be considered., (© 2021. The Author(s).)

Objectives: Postoperative pulmonary function is difficult to predict accurately, because it changes from the time of the operation and is also affected by various factors. The objective of this study was to assess the accuracy of predicted postoperative forced expiratory volume in 1 s (FEV1) at different postoperative times after lobectomy., Methods: This retrospective study enrolled 104 patients who underwent lobectomy by video-assisted thoracic surgery. Pulmonary function tests were performed preoperatively and postoperatively at 3, 6 and 12 months. We investigated time-dependent changes in FEV1. In addition, the ratio of measured to predicted postoperative FEV1 calculated by the subsegmental method was evaluated to identify the factors associated with variations in postoperative FEV1., Results: Compared with the predicted postoperative FEV1, the measured postoperative FEV1 was 8% higher at 3 months, 11% higher at 6 months and 13% higher at 12 months. The measured postoperative FEV1 significantly increased from 3 to 6 months (P = 0.002) and from 6 to 12 months (P = 0.015) after lobectomy resected lobe, smoking history and body mass index were significant factors associated with the ratio of measured to predicted postoperative FEV1 at 12 months (P < 0.001, P = 0.036 and P = 0.025, respectively)., Conclusions: Postoperative FEV1 increased up to 12 months after lobectomy by video-assisted thoracic surgery. The predicted postoperative pulmonary function was underestimated after 3 months, particularly after lower lobectomy., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objective: Electroconvulsive therapy (ECT) is provided in real-world clinical settings for patients lacking capacity for consent. The aim of this study was to investigate the clinical characteristics and clinical effectiveness of ECT in this population., Methods: A retrospective chart review was conducted to collect data from patients who received ECT to treat their depressive episodes between April 2012 and March 2019. Differences in clinical characteristics and short-/long-term clinical outcomes between patients who received ECT with their relatives' consent and patients who received ECT by their own consent were examined. The short-/long-term clinical outcomes were determined by clinical global impression scores and readmission rate, respectively., Results: Of 168 patients with depressive episodes, 34 (20.2%) received ECT with their relatives' consent. Those patients were older, had lower body mass index, and had shorter episode duration. They also exhibited more frequent psychotic, melancholic, and catatonic features. The main indication for ECT in this population was the need for rapid recovery. Patients lacking capacity for consent showed similar remission (61.8%) and response (82.4%) rates to those with capacity for consent. Readmission rate was not significantly different between groups., Conclusions: There were no significant differences in short-/long-term ECT effectiveness between patients with/without capacity for consent. Electroconvulsive therapy is the only established and effective treatment in clinical settings for the most severe cases, wherein patients are incapable of giving consent but need rapid recovery. A general rejection of this practice due to concerns surrounding consent may be unethical under the ethical principles of medical care., Competing Interests: The authors have no conflicts of interest or financial disclosures to report., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Electroconvulsive therapy (ECT) is the most effective treatment for severe depression. Recent neuroimaging studies have consistently reported that ECT induces volume increases in widely distributed brain regions. However, it still remains unclear about ECT-induced volume changes associated with clinical improvement., Methods: Longitudinal assessments of structural magnetic resonance imaging were conducted in 48 participants. Twenty-seven elderly melancholic depressed individuals (mean 67.5 ± 8.1 years old; 19 female) were scanned before (TP1) and after (TP2) ECT. Twenty-one healthy controls were also scanned twice. Whole-brain gray matter volume (GMV) was analyzed via group (remitters, nonremitters, and controls) by time (TP1 and TP2) analysis of covariance to identify ECT-related GMV changes and GMV changes specific to remitters. Within-subject and between-subjects correlation analyses were conducted to investigate the associations between clinical improvement and GMV changes. Depressive symptoms were evaluated using the 17-item Hamilton Depression Rating Scale (HAM-D), and remission was defined as HAM-D total score ≤ 7., Results: Bilateral ECT increased GMV in multiple brain regions bilaterally regardless of clinical improvement. Remitters showed a larger GMV increase in the right-lateralized frontolimbic brain regions compared to nonremitters and healthy controls. GMV changes in the right hippocampus/amygdala and right middle frontal gyrus showed correlations with clinical improvement in within-/between-subjects correlation analyses., Conclusions: ECT-induced GMV increase in the right frontolimbic regions was associated with clinical remission., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Viral proteins interact with different sets of host cell components throughout the viral life cycle and are known to localize to the intracellular membraneless organelles (MLOs) of the host cell, where formation/dissolution is regulated by phase separation of intrinsically disordered proteins and regions (IDPs/IDRs). Viral proteins are rich in IDRs, implying that viruses utilize IDRs to regulate phase separation of the host cell organelles and augment replication by commandeering the functions of the organelles and/or sneaking into the organelles to evade the host immune response. This review aims to integrate current knowledge of the structural properties and intracellular localizations of viral IDPs to understand viral strategies in the host cell. First, the properties of viral IDRs are reviewed and similarities and differences with those of eukaryotes are described. The higher IDR content in viruses with smaller genomes suggests that IDRs are essential characteristics of viral proteins. Then, the interactions of the IDRs of flaviviruses with the MLOs of the host cell are investigated with emphasis on the viral proteins localized in the nucleoli and stress granules. Finally, the possible roles of viral IDRs in regulation of the phase separation of organelles and future possibilities for antiviral drug development are discussed.

Insufficient autophagic degradation has been implicated in accelerated cellular senescence during chronic obstructive pulmonary disease (COPD) pathogenesis. Aging-linked and cigarette smoke (CS)-induced functional deterioration of lysosomes may be associated with impaired autophagy. Lysosomal membrane permeabilization (LMP) is indicative of damaged lysosomes. Galectin-3 and tripartite motif protein (TRIM) 16 play a cooperative role in recognizing LMP and inducing lysophagy, a lysosome-selective autophagy, to maintain lysosome function. In this study, we sought to examine the role of TRIM16-mediated lysophagy in regulating CS-induced LMP and cellular senescence during COPD pathogenesis by using human bronchial epithelial cells and lung tissues. CS extract (CSE) induced lysosomal damage via LMP, as detected by galectin-3 accumulation. Autophagy was responsible for modulating LMP and lysosome function during CSE exposure. TRIM16 was involved in CSE-induced lysophagy, with impaired lysophagy associated with lysosomal dysfunction and accelerated cellular senescence. Airway epithelial cells in COPD lungs showed an increase in lipofuscin, aggresome and galectin-3 puncta, reflecting accumulation of lysosomal damage with concomitantly reduced TRIM16 expression levels. Human bronchial epithelial cells isolated from COPD patients showed reduced TRIM16 but increased galectin-3, and a negative correlation between TRIM16 and galectin-3 protein levels was demonstrated. Damaged lysosomes with LMP are accumulated in epithelial cells in COPD lungs, which can be at least partly attributed to impaired TRIM16-mediated lysophagy. Increased LMP in lung epithelial cells may be responsible for COPD pathogenesis through the enhancement of cellular senescence., (Copyright © 2021 by The American Association of Immunologists, Inc.)

Immunoevasins are viral proteins that prevent antigen presentation on major histocompatibility complex (MHC) class I, thus evading host immune recognition. Hepatitis C virus (HCV) evades immune surveillance to induce chronic infection; however, how HCV-infected hepatocytes affect immune cells and evade immune recognition remains unclear. Herein, we demonstrate that HCV core protein functions as an immunoevasin. Its expression interfered with the maturation of MHC class I molecules catalyzed by the signal peptide peptidase (SPP) and induced their degradation via HMG-CoA reductase degradation 1 homolog, thereby impairing antigen presentation to CD8 + T cells. The expression of MHC class I in the livers of HCV core transgenic mice and chronic hepatitis C patients was impaired but was restored in patients achieving sustained virological response. Finally, we show that the human cytomegalovirus US2 protein, possessing a transmembrane region structurally similar to the HCV core protein, targets SPP to impair MHC class I molecule expression. Thus, SPP represents a potential target for the impairment of MHC class I molecules by DNA and RNA viruses., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Background: Catamenial pneumothorax is generally uncommon, with an incidence of less than 3-6% in women with spontaneous pneumothorax. As few cases of catamenial pneumothorax with diaphragmatic defect and liver herniation have been reported, this case report may be useful for understanding the cause and treatment. This case highlights the importance of the approach for liver hernia in patients with catamenial pneumothorax and endometriosis., Case Presentation: We report a case of catamenial pneumothorax in a 43-year-old woman with diaphragmatic partial liver hernia who was treated with thoracoscopic surgery. She was diagnosed with a right pneumothorax at menstruation onset. Chest computed tomography showed a nodule protruding above the right diaphragm. We performed thoracoscopic surgery to treat the persistent air leak and biopsied the nodule on the right diaphragm. There were blueberry spots on the diaphragm; the nodule was found to be the herniated liver. The diaphragmatic defect was sutured. Histological examination of the tissue near the partial prolapsed liver revealed endometrial tissue., Conclusions: It is speculated that ectopic endometrial tissue in the diaphragm will periodically necrose to become a diaphragmatic tear, which is a pathway for air to enter the thoracic cavity and eventually a herniated liver. Thoracoscopic surgery should be considered in patients with catamenial pneumothorax when a diaphragmatic lesion is suspected.

Proteins newly synthesized from messenger RNA undergo Posttranslational modifications (PTMs) such as phosphorylation, glycosylation, methylation, and ubiquitination. These PTMs have important roles in protein stability, localization, and conformation and have been reported to be involved in hepatitis B virus (HBV) propagation. Although ubiquitination plays an essential role in HBV life cycles, the involvement of ubiquitin-like proteins (UBLs) in HBV life cycles has been understudied. Through comprehensive gain- and loss-of-function screening of UBLs, we observed that neddylation, a PTM in which neural precursor cell, expressed developmentally downregulated 8 (NEDD8) is conjugated to substrate proteins, was required for efficient HBV propagation. We also found that overexpression of sentrin-specific protease 8 (SENP8), which cleaves conjugated NEDD8, suppressed HBV propagation. Further, the catalytic activity of SENP8 was required for the suppression of HBV propagation. These results indicated that the reduction of neddylation negatively regulated HBV propagation. In addition, we demonstrated that suppression of HBV propagation via SENP8 overexpression was independent of hepatitis B protein X (HBx) and HBV promoter activity. Therefore, our data suggested that neddylation plays an important role in the late stages of HBV life cycles., (© 2021 The Societies and John Wiley & Sons Australia, Ltd.)

Objective: Complete pleural symphysis from adhesions is a troublesome intraoperative finding. A blunted costophrenic angle without pleural effusion is an indicator of prior pleural disease; however, the diagnostic accuracy of blunted costophrenic angles for complete pleural symphysis is unclear. This study to determine whether complete pleural symphysis is predicted by the finding of a blunted costophrenic angle., Methods: The operative records of patients who underwent thoracic cavity surgery were retrospectively reviewed. Cases with ipsilateral pleural effusion identified using preoperative computed tomography were excluded. A receiver-operating characteristic curve for complete pleural symphysis was generated to determine the optimal cut-off value of the costophrenic angle based on intraoperative findings for adhesions. The cases were then divided into blunted and sharp costophrenic angle groups, and the sensitivity, specificity, accuracy, positive likelihood ratio, and negative likelihood ratio for complete pleural symphysis were calculated for both groups., Results: In total, 1204 thoracic sides (709 right, 495 left) of 1186 cases were reviewed. According to the receiver-operating characteristic curve, the optimal cut-off value of the costophrenic angle was 51°. The rate of complete pleural symphysis was significantly higher in the blunted group than in the sharp group (p < 0.001). The sensitivity, specificity, accuracy, positive likelihood ratio, and negative likelihood ratio were 70.7, 96.1, 95.3%, 18.3, and 0.30, respectively., Conclusions: Complete pleural symphysis was predicted by a blunted costophrenic angle with moderate sensitivity and high specificity, accuracy, and positive likelihood ratio. Evaluation of the costophrenic angle could, therefore, be an efficient, simple, and convenient screening tool.

Introduction: We examined the long-term efficacy and safety of nivolumab, a human monoclonal antibody that inhibits interactions between the programmed cell death protein-1 receptor and its ligands (programmed death-ligand 1 and programmed death-ligand 2), in Japanese patients with malignant pleural mesothelioma (MPM)., Methods: Japanese patients with previously treated MPM (one or two regimens) were enrolled in a single-arm, phase 2 study and received nivolumab intravenously 240 mg every 2 weeks until progressive disease or unacceptable toxicity. The primary end point was the centrally assessed objective response rate. Other end points included overall survival (OS), progression-free survival (PFS), treatment-related adverse events, and patient-reported outcomes (Lung Cancer Symptom Scale for mesothelioma and EuroQOL visual analog scale). Patient enrollment started on June 16, 2016. Here, we report 3-year follow-up data (cutoff date: November 12, 2019)., Results: Thirty-four patients were enrolled. The centrally assessed objective response rate was previously reported (29.4%). The 2- and 3-year OS rates were 35.3% and 23.5%, respectively, and the corresponding PFS rates were 17.0% and 12.7%. Median OS and PFS were 17.3 and 5.9 months, respectively. Eight patients were alive at 3 years of follow-up. Nivolumab was well tolerated and no new safety signals were found. The patient-reported outcomes were maintained without marked deteriorations during the study., Conclusions: Our results reveal clinically relevant long-term efficacy and safety of nivolumab for the treatment of MPM., (© 2021 The Authors.)