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Purpose: Despite a global decrease in the number of COVID-19 patients, early prediction of the clinical course for optimal patient care remains challenging. Recently, the usefulness of image generation for medical images has been investigated. This study aimed to generate short-term follow-up chest CT images using a latent diffusion model in patients with COVID-19., Materials and Methods: We retrospectively enrolled 505 patients with COVID-19 for whom the clinical parameters (patient background, clinical symptoms, and blood test results) upon admission were available and chest CT imaging was performed. Subject datasets (n = 505) were allocated for training (n = 403), and the remaining (n = 102) were reserved for evaluation. The image underwent variational autoencoder (VAE) encoding, resulting in latent vectors. The information consisting of initial clinical parameters and radiomic features were formatted as a table data encoder. Initial and follow-up latent vectors and the initial table data encoders were utilized for training the diffusion model. The evaluation data were used to generate prognostic images. Then, similarity of the prognostic images (generated images) and the follow-up images (real images) was evaluated by zero-mean normalized cross-correlation (ZNCC), peak signal-to-noise ratio (PSNR), and structural similarity (SSIM). Visual assessment was also performed using a numerical rating scale., Results: Prognostic chest CT images were generated using the diffusion model. Image similarity showed reasonable values of 0.973 ± 0.028 for the ZNCC, 24.48 ± 3.46 for the PSNR, and 0.844 ± 0.075 for the SSIM. Visual evaluation of the images by two pulmonologists and one radiologist yielded a reasonable mean score., Conclusions: The similarity and validity of generated predictive images for the course of COVID-19-associated pneumonia using a diffusion model were reasonable. The generation of prognostic images may suggest potential utility for early prediction of the clinical course in COVID-19-associated pneumonia and other respiratory diseases., Competing Interests: Declarations. Competing interests: The authors declare that they have no competing interests. Ethical statement: This retrospective multicenter study was approved by the Institutional Review Boards of Chiba University (No. 4074 Date 2021/11/24) and Chiba Aoba Municipal Hospital (No. 20200301). The study was conducted in accordance with the principles of the Declaration of Helsinki. The institutional review boards of all hospital institutions included in the present study provided ethical approval. The requirement for written informed consent was waived due to the characteristics of the retrospective study., (© 2024. The Author(s).)

Oncogenic transformation of normal cells is caused by mutations and chromosomal abnormalities in cancer-related genes. Enzootic bovine leukosis (EBL) is a malignant B-cell lymphoma caused by bovine leukemia virus (BLV) infection in cattle. Although a small fraction of BLV-infected cattle develops EBL after a long latent period, the mechanisms for oncogenesis in EBL cattle remain largely unknown. In this study, we analyzed the types and patterns of somatic mutations in cancer cells from 36 EBL cases, targeting 21 cancer-related genes. Various somatic mutations were identified in eight genes, TP53 , KMT2D , CREBBP , KRAS , PTEN , NOTCH1 , MYD88 , and CARD11 . In addition, TP53 gene was found to be mutated in 69.4% of EBL cases, with most being biallelic mutations. In some cases, associations were observed between the ages at which cattle had developed EBL and somatic mutation patterns; young onset of EBL possibly occurs due to high impact mutations affecting protein translation and biallelic mutations. Furthermore, nucleotide substitution patterns indicated that cytosine at CpG sites tended to be converted to thymine in many EBL cases, which was considered to be the result of spontaneous deamination of 5-methylcytosine. These results demonstrate how somatic mutations have occurred in cancer cells leading to EBL development, thereby explaining its pathogenic mechanism. These findings will contribute to a better understanding and future elucidation of disease progression in BLV infection.IMPORTANCEEnzootic bovine leukosis (EBL) is a malignant and lethal disease in cattle. Currently, there are no effective vaccines or therapeutic methods against bovine leukemia virus (BLV) infection, resulting in severe economic losses in livestock industry. This study provides a renewed hypothesis to explain the general mechanisms of EBL onset by combining the previous finding that several integration sites of BLV provirus can affect the increase in survival and proliferation of infected cells. We demonstrate that two additional random events are necessary for oncogenic transformation in infected cell clones, elucidating the reason why only few infected cattle develop EBL. Further exploration of somatic mutation and BLV integration sites could support this hypothesis more firmly, potentially contributing to the development of novel control methods for EBL onset., Competing Interests: The authors declare no conflict of interest.

Background: The Kerlan-Jobe Orthopaedic Clinic shoulder and elbow score (KJOC) is sensitive enough to detect subtle changes in the functional level of the shoulder or elbow in overhead athletes. However, a Japanese version of the KJOC is not yet available. Moreover, the original KJOC uses a visual analog scale (VAS) assessment format that requires a print version so that users can add a check mark along a horizontal line. The KJOC can be completed using online tools such as Google Forms if a 10-point scale format can be used with comparable results., Purposes: To (1) translate and cross-culturally adapt the KJOC into Japanese (KJOC-J) and assess its validity and (2) evaluate the correlation between a standard VAS format and a 10-point scale format (KJOC-J10)., Study Design: Cohort study (Diagnosis); Level of evidence, 3., Methods: In total, 318 athletes participated in the validation study, 255 in the test-retest reliability study for the KJOC-J, and 273 in the validation study for the KJOC-J10. Internal consistency was evaluated using the Cronbach alpha. Validity was evaluated by calculating the correlation between the KJOC-J and the Disability of the Arm, Shoulder and Hand (DASH). Test-retest reliability was assessed using the intraclass correlation coefficient (ICC). The validity of the KJOC-J10 was evaluated by calculating the correlation between the KJOC-J10 and KJOC-J., Results: The Cronbach alpha was 0.914, indicating good internal consistency. The KJOC-J was moderately correlated with the DASH ( r = -0.581; P < .001) and had good test-retest reliability (ICC, 0.874). A strong correlation was found between the KJOC-J and KJOC-J10 ( r = 0.846; P < .001)., Conclusion: The study results demonstrated good internal consistency, validity, and reliability for the KJOC-J, indicating that it is a valid assessment tool for shoulder and elbow functions in Japanese overhead athletes. Moreover, a strong correlation was found between the VAS and 10-point formats of the KJOC-J., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: Research support was received from the Project for Establishment of Sports Medicine and Science Support System in Local Communities 2023 through the Japan Sports Agency. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2024.)

Purpose: In a cadaveric model, a comparison was made of the strength of a suture method for collateral ligaments (the N method) with that of simple sutures using suture anchors for the repair of collateral ligaments in the proximal interphalangeal joint., Methods: We obtained 72 fingers from 18 upper limbs of fresh-frozen cadavers and compared the left and right sides of the same specimens. In experiment 1, we examined the rupture strength and rupture sites of intact collateral ligaments in 24 fingers. In experiment 2, we compared the rupture strength and failure modes of the N method (three locking sutures) with those of simple sutures (S group) on 32 fingers. In experiment 3, we examined the rupture strength and failure modes between the N method with three locking sutures (N3 group) and the N method with two locking sutures (N2 group) on 16 fingers. All the experiments involved mechanical testing by applying lateral stress to the collateral ligaments at a rate of 1 mm/s using testing equipment., Results: In Experiment 1, the mean rupture strength of intact collateral ligaments was 80.6 ± 27.5 N. Proximal tears were the most common rupture sites. In Experiment 2, the mean rupture strength was significantly higher in the N group (46.3 ± 19.2 N) than in the S group (24.1 ± 12.7 N). In the N group, suture breakage occurred more frequently than in the S group, whereas in the S group, there was a higher incidence of suture cut out. In Experiment 3, the N3 and N2 groups exhibited nearly identical rupture strength values., Conclusions: This study showed that the N method had better rupture strength than the simple suture method following finger collateral ligament repair., Clinical Relevance: The outcome provides useful information for informing the choice of suture method in clinical practice., Competing Interests: Conflicts of Interest No benefits in any form have been received or will be received related directly to this article., (Copyright © 2024 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

We previously reported that hepatitis C virus (HCV) infection or HCV core protein expression induces HOX gene expression by impairing histone H2A monoubiquitination via a proteasome-dependent reduction in the level of RNF2, a key catalytic component of polycomb repressive complex 1 (H. Kasai, K. Mochizuki, T. Tanaka, A. Yamashita, et al., J Virol 95:e01784-20, 2021, https://doi.org/10.1128/jvi.01784-20). In this study, we aimed to investigate the mechanism by which HCV infection accelerates RNF2 degradation. Yeast two-hybrid screening and an immunoprecipitation assay revealed that RNF2 is a PA28γ-binding protein. The proteasome activator PA28γ destabilized the RNF2 protein in a proteasome-dependent manner, since RNF2 degradation was impaired by PA28γ knockout or MG132 treatment. HCV infection or core protein expression reduced the levels of RNF2 and histone H2A K119 monoubiquitination and induced the expression of HOX genes in the presence of PA28γ, while PA28γ knockout reversed these changes. Treatment with a lysine acetyltransferase inhibitor inhibited the acetylation of PA28γ at K195 and the degradation of the RNF2 protein, while treatment with a lysine deacetylase inhibitor accelerated these events in a PA28γ-dependent manner. RNF2 protein degradation was increased by expression of the acetylation mimetic PA28γ mutant but not by expression of the acetylation-defective mutant or the proteasome activation-defective mutant. Furthermore, HCV infection or core protein expression facilitated the interaction between PA28γ and the lysine acetyltransferase CBP/p300 and then accelerated PA28γ acetylation and heptazmerization to promote RNF2 degradation. These data suggest that HCV infection accelerates the acetylation-dependent heptamerization of PA28γ to increase the proteasomal targeting of RNF2.IMPORTANCEHCV is a causative agent of HCV-related liver diseases, including hepatic steatosis, cirrhosis, and hepatocellular carcinoma. PA28γ, which, in heptameric form, activates the 20S core proteasome for the degradation of PA28γ-binding proteins, is responsible for HCV-related liver diseases. HCV core protein expression or HCV infection accelerates RNF2 degradation, leading to the induction of HOX gene expression via a decrease in the level of H2Aub on HOX gene promoters. However, the mechanism of RNF2 degradation in HCV-infected cells has not been clarified. The data presented in this study suggest that PA28γ acetylation and heptamerization are promoted by HCV infection or by core protein expression to activate the proteasome for the degradation of RNF2 and are responsible for HCV propagation. This study provides novel insights valuable for the development of therapies targeting both HCV propagation and HCV-related diseases., Competing Interests: The authors declare no conflict of interest.

Competing Interests: The authors declare no conflict of interest.

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Pelvis experiences changes in its orientation due to the alignment of the hip joint and spine, and its orientation might affect both joints. Pelvic tilt on the sagittal plane has been widely discussed; however, the pelvis is oriented also on the coronal and horizontal planes. This study aimed to examine how stress distribution on intact hip joint changes under the three-dimensional pelvic orientation., Methods: Computed tomography data of five patients with unilateral pelvic girdle were analyzed. Thirteen models were evaluated by the MECHANICAL FINDER: neutral position at 0°; 10° and 20° anterior and posterior pelvic tilt; 10° and 20° pelvic hike and drop; 10° and 20° pelvic forward and backward rotation. Stress assessment was performed in four parts of the acetabulum: anterosuperior, posterosuperior, posteroinferior, and central parts., Results: Compared with the neutral position, the mean value of the equivalent stress and maximum principal stress in the anterosuperior part significantly increased by 1.51 times and 1.57 times at 20° posterior tilt, respectively. The maximum principal stress in the anterosuperior part significantly increased by 1.44 times at 20° hike. A significant increase of 1.45 times was found in the maximum principal stress in the anterosuperior part at 20° forward rotation., Conclusions: Local stress accumulated in the anterosuperior acetabulum at the posterior pelvic tilt, pelvic hike, and pelvic forward rotation, which might lead to hip overload. The effect of posterior pelvic tilt appears to be greater for the hip joint than at the pelvic hike or forward rotation., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Importance: This report details a case of effectively managing severe panic attacks in a panic disorder (PD) patient with agoraphobia by acupuncture treatment., Case Presentation: A 38-year-old Japanese woman suffering from PD with agoraphobia presented at our acupuncture clinic with complaints of repeated panic attacks and anxiety. Initially starting to experience symptoms in her late teens, she avoided psychiatric consultation due to reluctance toward psychotropic medications. An unbiased psychiatrist used the Panic Disorder Severity Scale (PDSS) to assess her PD severity. The PDSS score decreased from 21 on the first to 12 points on the sixth visit. The patient experienced reduced frequency and severity of panic attacks, with restored confidence to go into public despite agoraphobia., Conclusions and Relevance: This is the first report to demonstrate the effectiveness of acupuncture on PD with agoraphobia using PDSS, suggesting its potential as a nonpharmacological treatment for patients with PD and agoraphobia.

Introduction: The SARS-CoV-2 pandemic has had a widespread and severe impact on society, yet there have also been instances of remarkable recovery, even in critically ill patients., Materials and Methods: In this study, we used single-cell RNA sequencing to analyze the immune responses in recovered and deceased COVID-19 patients during moderate and critical stages., Results: Expanded T cell receptor (TCR) clones were predominantly SARS-CoV-2-specific, but represented only a small fraction of the total repertoire in all patients. In contrast, while deceased patients exhibited monoclonal B cell receptor (BCR) expansions without COVID-19 specificity, survivors demonstrated diverse and specific BCR clones. These findings suggest that neither TCR diversity nor BCR monoclonal expansions are sufficient for viral clearance and subsequent recovery. Differential gene expression analysis revealed that protein biosynthetic processes were enriched in survivors, but that potentially damaging mitochondrial ATP metabolism was activated in the deceased., Conclusion: This study underscores that BCR repertoire diversity, but not TCR diversity, correlates with favorable outcomes in COVID-19., 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 © 2024 Paran, Oyama, Khasawneh, Ai, Ismanto, Sherif, Saputri, Ono, Saita, Takei, Horiuchi, Yagi, Matsuura, Okazaki, Takahashi, Standley, Tabe and Naito.)

KEGG (https://www.kegg.jp/) is a database resource for representation and analysis of biological systems. Pathway maps are the primary dataset in KEGG representing systemic functions of the cell and the organism in terms of molecular interaction and reaction networks. The KEGG Orthology (KO) system is a mechanism for linking genes and proteins to pathway maps and other molecular networks. Each KO is a generic gene identifier and each pathway map is created as a network of KO nodes. This architecture enables KEGG pathway mapping to uncover systemic features from KO assigned genomes and metagenomes. Additional roles of KOs include characterization of conserved genes and conserved units of genes in organism groups, which can be done by taxonomy mapping. A new tool has been developed for identifying conserved gene orders in chromosomes, in which gene orders are treated as sequences of KOs. Furthermore, a new dataset called VOG (virus ortholog group) is computationally generated from virus proteins and expanded to proteins of cellular organisms, allowing gene orders to be compared as VOG sequences as well. Together with these datasets and analysis tools, new types of pathway maps are being developed to present a global view of biological processes involving multiple organism groups., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy. We report an extremely rare case of CTS associated with a bifid median nerve and palmaris profundus muscle. A 68-year-old man presented with numbness and pain in the right hand. Intraoperatively, a bifid median nerve was identified, with the ulnar branch severely compressed by the palmaris profundus muscle. The muscle was resected, leading to symptom resolution. Anatomical variations of the median nerve and anomalous muscles should be considered in CTS. Preoperative imaging and open carpal tunnel release are recommended to identify and address such variations., Competing Interests: The authors have no financial interest to declare in relation to the content of this article. During the preparation of this work, the author used ChatGPT4 to convert the text from Japanese to English. After using this tool, the author reviewed and edited the content as needed. Subsequently, the author takes full responsibility for the content of this article., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Background and Objectives: A recent Japanese phase three clinical trial for lung cancer suggested a possible advantage of segmentectomy over lobectomy in terms of death from other diseases. This study aimed to compare the risk of death from other diseases based on surgical procedures in lung cancer patients without recurrence., Methods: We retrospectively reviewed 2121 patients without disease recurrence after curative resection for lung cancer at our institution. Patient characteristics and overall survival were compared between sublobar resection and lobectomy., Results: The sublobar group (n = 595) had a significantly higher proportion of women, non-smokers, patients without comorbidities, patients with a history of other cancers, and patients with earlier-staged disease when compared with the lobectomy group (n = 1526). The overall survival was significantly longer in the sublobar group than in the lobectomy group (p = 0.0034). After adjusting for background characteristics in an analysis of 488 patients, the overall survival had a trend to be longer in the sublobar group than in the lobectomy group (p = 0.071)., Conclusions: Our results suggested that the risk of death from other diseases was potentially higher after lobectomy than after sublobar resection. Although several clinical factors could influence the results, these results may support the benefit of sublobar resection, assuming that the curability of both procedures is similar., (© 2024 Wiley Periodicals LLC.)

Background: The appropriate extent of hilar lymph node (LN) dissection in segmentectomy for lung cancer has not yet been fully investigated. Herein, we assessed the patterns of LN metastasis using network analyses., Methods: Patients with nodal metastases of non-small-cell lung cancer measuring ≤30 mm in diameter who underwent anatomical resection were included. The assumed pathways of metastasis were visualized using Cytoscape software. Metastasis to hilar (#10) or interlobar (#11) LNs but not to more peripheral ones was defined as skip N1 metastasis., Results: A total of 322 patients were included, with 123 of them having pleural invasive tumors and 32 having intrapulmonary metastases. There were 130 patients with pN1 disease and 192 with pN2 disease. The overall proportion of patients with skip N1 metastasis was 17%. Patients with lower lobe tumors had more frequent skip N1 metastasis than those with upper lobe tumors (31% vs. 10%, P<0.001) but had less frequent skip N2 metastasis (10% vs. 20%, P=0.02). The rates of skip metastasis to #11i in the right S6 tumor and right S9-10 tumor were unexpectedly high (22% and 17%, respectively). Similarly, skip metastasis to #11 in the left S6 tumor was relatively high (16%). There was a significant difference in the frequency of skip LN metastasis between tumors with and without pleural invasion (44% vs. 27%, P=0.001)., Conclusions: The pattern of LN metastasis differed according to the localized segment of the tumor and the pleural invasion status., 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-24-944/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

This cross-sectional study investigates the association between long working hours, short sleep duration, and mental health among Japanese physicians. We enrolled 232 Japanese physicians. We used the Brief Job Stress Questionnaire to assess high-stress status, and the Japanese version of the Center for Epidemiologic Studies Depression scale to assess depressive status. Daily sleep duration (DSD) and weekly working hours (WWHs) were collected using a self-administered questionnaire. Multivariable-adjusted logistic regression analysis was performed to examine the association of the combined categories of DSD and WWHs with high-stress and depressive status. Compared to physicians with WWHs <80 h and DSD ≥6 h, the multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of high-stress status for those with WWHs ≥80 and DSD ≥6, WWHs <80 and DSD <6, and WWHs ≥80 and DSD <6 were 2.76 (0.97-7.87), 3.36 (1.53-7.40), and 3.92 (1.52-10.14), respectively. The respective ORs (CIs) of depressive status were 1.82 (0.42-7.81), 4.03 (1.41-11.53), and 4.69 (1.33-16.62). The results showed that regardless of working long hours or not, physicians with DSD <6 h had significantly higher stress and depressive status, suggesting that not only regulating long working hours but also ensuring adequate sleep duration is important for preventing physicians' mental health.

Competing Interests: None disclosed.

Whereas severe COVID-19 is often associated with elevated autoantibody titers, the underlying mechanism behind their generation has remained unclear. Here we report clonal composition and diversity of autoantibodies in humoral response to SARS-CoV-2. Immunoglobulin repertoire analysis and characterization of plasmablast-derived monoclonal antibodies uncovered clonal expansion of plasmablasts producing cardiolipin (CL)-reactive autoantibodies. Half of the expanded CL-reactive clones exhibited strong binding to SARS-CoV-2 antigens. One such clone, CoV1804, was reactive to both CL and viral nucleocapsid (N), and further showed anti-nucleolar activity in human cells. Notably, antibodies sharing genetic features with CoV1804 were identified in COVID-19 patient-derived immunoglobulins, thereby constituting a novel public antibody. These public autoantibodies had numerous mutations that unambiguously enhanced anti-N reactivity, when causing fluctuations in anti-CL reactivity along with the acquisition of additional self-reactivities, such as anti-nucleolar activity, in the progeny. Thus, potentially CL-reactive precursors may have developed multiple self-reactivities through clonal selection, expansion, and somatic hypermutation driven by viral antigens. Our results revealed the nature of autoantibody production during COVID-19 and provided novel insights into the origin of virus-induced autoantibodies., (© 2024 Sakakibara et al.)

A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes mild-to-severe respiratory symptoms, including acute respiratory distress. Despite remarkable efforts to investigate the virological and pathological impacts of SARS-CoV-2, many of the characteristics of SARS-CoV-2 infection still remain unknown. The interferon-inducible ubiquitin-like protein ISG15 is covalently conjugated to several viral proteins to suppress their functions. It was reported that SARS-CoV-2 utilizes its papain-like protease (PLpro) to impede ISG15 conjugation, ISGylation. However, the role of ISGylation in SARS-CoV-2 infection remains unclear. We aimed to elucidate the role of ISGylation in SARS-CoV-2 replication. We observed that the SARS-CoV-2 nucleocapsid protein is a target protein for the HERC5 E3 ligase-mediated ISGylation in cultured cells. Site-directed mutagenesis reveals that the residue K374 within the C-terminal spacer B-N3 (SB/N3) domain is required for nucleocapsid-ISGylation, alongside conserved lysine residue in MERS-CoV (K372) and SARS-CoV (K375). We also observed that the nucleocapsid-ISGylation results in the disruption of nucleocapsid oligomerization, thereby inhibiting viral replication. Knockdown of ISG15 mRNA enhanced SARS-CoV-2 replication in the SARS-CoV-2 reporter replicon cells, while exogenous expression of ISGylation components partially hampered SARS-CoV-2 replication. Taken together, these results suggest that SARS-CoV-2 PLpro inhibits ISGylation of the nucleocapsid protein to promote viral replication by evading ISGylation-mediated disruption of the nucleocapsid oligomerization.IMPORTANCEISG15 is an interferon-inducible ubiquitin-like protein that is covalently conjugated to the viral protein via specific Lys residues and suppresses viral functions and viral propagation in many viruses. However, the role of ISGylation in SARS-CoV-2 infection remains largely unclear. Here, we demonstrated that the SARS-CoV-2 nucleocapsid protein is a target protein for the HERC5 E3 ligase-mediated ISGylation. We also found that the residue K374 within the C-terminal spacer B-N3 (SB/N3) domain is required for nucleocapsid-ISGylation. We obtained evidence suggesting that nucleocapsid-ISGylation results in the disruption of nucleocapsid-oligomerization, thereby suppressing SARS-CoV-2 replication. We discovered that SARS-CoV-2 papain-like protease inhibits ISG15 conjugation of nucleocapsid protein via its de-conjugating enzyme activity. The present study may contribute to gaining new insight into the roles of ISGylation-mediated anti-viral function in SARS-CoV-2 infection and may lead to the development of more potent and selective inhibitors targeted to SARS-CoV-2 nucleocapsid protein., Competing Interests: The authors declare no conflict of interest.

Secondary spontaneous pneumothorax (SSP) due to bevacizumab has been reported in other malignancies but not in cervical cancer. We present the case of a 57-year-old woman with stage IIIB cervical cancer who developed SSP during bevacizumab chemotherapy. Despite complete remission with cisplatin-based chemoradiotherapy, she experienced a recurrence 9 months later. A thoracoscopic surgery was performed to remove a lung nodule and bulla. Subsequently, local cervical lesion recurrence and lung metastases were noted, and paclitaxel and carboplatin combined with bevacizumab were administered. After two cycles, a grade-1 left pneumothorax occurred, attributed to bevacizumab-induced tissue fragility. The patient improved within 7 days with conservative management. Bevacizumab was discontinued, and pneumothorax did not recur. This case highlights the rare occurrence of SSP in patients with cervical cancer treated with bevacizumab and underscores the importance of appropriate management of such patients, especially those who have undergone early thoracic surgery., Competing Interests: Conflict of interestNo conflicts of interest., (© The Author(s) under exclusive licence to The Japan Society of Clinical Oncology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Aims: While the prevalence of transthyretin-derived amyloid cardiomyopathy (ATTR-CM) is on the rise, detailed understanding of its morphological and functional characteristics within the left ventricle (LV) across heart failure (HF) remains limited., Methods and Results: Utilizing two-dimensional (2D) speckle-tracking echocardiography, we assessed longitudinal strain (LS) in 63 histology-confirmed ATTR-CM patients. Additionally, cardiac magnetic resonance (CMR) images measured native T1 and extracellular volume (ECV), compared with LS across 18 LV segments. Patients were categorized into three groups based on HF status: Group 1 (no HF symptoms), Group 2 (HF with preserved LV ejection fraction), and Group 3 (HF with reduced LV ejection fraction). LS analysis unveiled susceptibility to deformation in the basal inferoseptal segment, persisting even in asymptomatic cases. CMR demonstrated increasing native T1 deviation, particularly evident in segments distant from the inferoseptal region. Contrastingly, maximal ECV was consistently observed in the basal and mid-ventricular inferior-septum, even in asymptomatic individuals. Segmental LS decline correlated with ECV expansion but not with native T1 values., Conclusion: Our findings suggest that the inferoseptal segment is highly susceptible to amyloid infiltration, and 2D speckle-tracking echocardiography and CMR may serve as a valuable tool for its early detection., Competing Interests: Conflict of interest: T.T. received lecture fees from Pfizer Japan Inc and Alnylam Japan. K.K. received lecture fees from Bayer Yakuhin, Daiichi-Sankyo, Novartis Pharma AG, Otsuka Pharmaceutical, Bristol-Myers K.K., and Kowa, as well as scholarship funds from Abbott Medical., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Exercise has positive effects on psychological well-being, with team sports often associated with superior mental health compared to individual sports. Augmented reality (AR) technology has the potential to convert solitary exercise into multi-person exercise. Given the role of oxytocin in mediating the psychological benefits of exercise and sports, this study aimed to investigate the impact of AR-based multi-person exercise on mood and salivary oxytocin levels., Methods: Fourteen participants underwent three distinct regimens: non-exercise (Rest), standard solitary cycling exercise (Ex), and AR-based multi-person cycling exercise (Ex+AR). In both Ex and Ex+AR conditions, participants engaged in cycling at a self-regulated pace to maintain a Rating of Perceived Exertion of 10. In the Ex+AR condition, participants' avatars were projected onto a tablet screen, allowing them to cycle alongside ten other virtual avatars in an AR environment. Mood states and saliva samples were collected before and immediately after each 10-minute regimen. Subsequently, salivary oxytocin levels were measured., Results: Notably, only the Ex+AR condition significantly improved mood states associated with depression-dejection and exhibited a non-significant trend toward suppressing anger-hostility in participants. Moreover, the Ex+AR condition led to a significant elevation in salivary oxytocin levels, while the Ex condition showed a non-significant trend toward an increase. However, changes in salivary oxytocin did not show a significant correlation with changes in mood states., Conclusions: These findings suggest that Ex+AR enhances mood states and promotes oxytocin release. AR-based multi-person exercise may offer greater psychological benefits compared to standard solitary exercise, although the relationship between oxytocin and mood changes remains inconclusive., Competing Interests: Declaration of competing interest The authors inform no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Coronavirus (CoV) possesses numerous functional cis-acting elements in its positive-strand genomic RNA. Although most of these RNA structures participate in viral replication, the functions of RNA structures in the genomic RNA of CoV in viral replication remain unclear. In this study, we investigated the functions of the higher-order RNA stem-loop (SL) structures SL5B, SL5C, and SL5D in the ORF1a coding region of Middle East respiratory syndrome coronavirus (MERS-CoV) in viral replication. Our approach, using reverse genetics of a bacterial artificial chromosome system, revealed that SL5B and SL5C play essential roles in the discontinuous transcription of MERS-CoV. In silico analyses predicted that SL5C interacts with a bulged stem-loop (BSL) in the 3' untranslated region, suggesting that the RNA structure of SL5C is important for viral RNA transcription. Conversely, SL5D did not affect transcription, but mediated the synthesis of positive-strand genomic RNA. Additionally, the RNA secondary structure of SL5 in the revertant virus of the SL5D mutant was similar to that of the wild-type, indicating that the RNA structure of SL5D can finely tune RNA replication in MERS-CoV. Our data indicate novel regulatory mechanisms of viral RNA transcription and replication by higher-order RNA structures in the MERS-CoV genomic RNA., (© 2024. The Author(s).)

Bovine viral diarrhea (BVD) is a serious disease in cattle and causes economic losses in the livestock industry. Bovine viral diarrhea virus (BVDV) is the causative agent of BVD and spreads among herds via persistently infected (PI) animals that shed large amounts of the virus throughout their lives. Hence, identifying, and culling PI animals and assessing the immune status against BVDV on farms are important strategies for controlling BVD. Additionally, estimating the time when individuals around PI animals were infected with the virus could also be supportive information to interpret a farm status. We herein constructed a BVDV-specific IgM capture ELISA using recombinant E2 antigen and applied it to detecting BVDV-specific IgM antibodies on farms with identified PI cattle. The IgM ELISA detected anti-BVDV IgM antibodies during approximately 2-3 weeks post infection and identified IgM-positive cattle on two farms with recognized PI cattle. Virus neutralization tests showed that almost all adult cattle had high virus neutralization antibodies against BVDV, and sero-positive and -negative cattle coexisted in young herds. In this situation, most of the IgM-positive cattle were in relatively young animals, implying that BVDV had been recently spreading in these young herds. Thus, our findings demonstrated that detecting IgM antibodies could be useful to know recent BVDV infection on farm on which PI cattle were identified., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Flaviviridae is a family of positive-stranded RNA viruses, including human pathogens, such as Japanese encephalitis virus (JEV), dengue virus (DENV), Zika virus (ZIKV), and West Nile virus (WNV). Nuclear localization of the viral core protein is conserved among Flaviviridae, and this feature may be targeted for developing broad-ranging anti-flavivirus drugs. However, the mechanism of core protein translocation to the nucleus and the importance of nuclear translocation in the viral life cycle remain unknown. We aimed to identify the molecular mechanism underlying core protein nuclear translocation. We identified importin-7 (IPO7), an importin-β family protein, as a nuclear carrier for Flaviviridae core proteins. Nuclear import assays revealed that core protein was transported into the nucleus via IPO7, whereas IPO7 deletion by CRISPR/Cas9 impaired their nuclear translocation. To understand the importance of core protein nuclear translocation, we evaluated the production of infectious virus or single-round-infectious-particles in wild-type or IPO7-deficient cells; both processes were significantly impaired in IPO7-deficient cells, whereas intracellular infectious virus levels were equivalent in wild-type and IPO7-deficient cells. These results suggest that IPO7-mediated nuclear translocation of core proteins is involved in the release of infectious virus particles of flaviviruses., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Itoh 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.)

We developed a surgical support system that visualises important microanatomies using artificial intelligence (AI). This study evaluated its accuracy in recognising the thoracic nerves during lung cancer surgery. Recognition models were created with deep learning using images precisely annotated for nerves. Computational evaluation was performed using the Dice index and the Jaccard index. Four general thoracic surgeons evaluated the accuracy of nerve recognition. Further, the differences in time lag, image quality and smoothness of movement between the AI system and surgical monitor were assessed. Ratings were made using a five-point scale. The computational evaluation was relatively favourable, with a Dice index of 0.56 and a Jaccard index of 0.39. The AI system was used for 10 thoracoscopic surgeries for lung cancer. The accuracy of thoracic nerve recognition was satisfactory, with a recall score of 4.5 ± 0.4 and a precision score of 4.0 ± 0.9. Though smoothness of motion (3.2 ± 0.4) differed slightly, nearly no difference in time lag (4.9 ± 0.3) and image quality (4.6 ± 0.5) between the AI system and the surgical monitor were observed. In conclusion, the AI surgical support system has a satisfactory accuracy in recognising the thoracic nerves., (© 2024. The Author(s).)

The potential involvement of the gut microbiota in metabolic dysfunction-associated steatohepatitis (MASH) pathogenesis has garnered increasing attention. In this study, we elucidated the link between high-fat/cholesterol/cholate-based (iHFC)#2 diet-induced MASH progression and gut microbiota in C57BL/6 mice using antibiotic treatments. Treatment with vancomycin (VCM), which targets gram-positive bacteria, exacerbated the progression of liver damage, steatosis, and fibrosis in iHFC#2-fed C57BL/6 mice. The expression levels of inflammation- and fibrosis-related genes in the liver significantly increased after VCM treatment for 8 weeks. F4/80 + macrophage abundance increased in the livers of VCM-treated mice. These changes were rarely observed in the iHFC#2-fed C57BL/6 mice treated with metronidazole, which targets anaerobic bacteria. A16S rRNA sequence analysis revealed a significant decrease in α-diversity in VCM-treated mice compared with that in placebo-treated mice, with Bacteroidetes and Firmicutes significantly decreased, while Proteobacteria and Verrucomicrobia increased markedly. Finally, VCM treatment dramatically altered the level and balance of bile acid (BA) composition in iHFC#2-fed C57BL/6 mice. Thus, the VCM-mediated exacerbation of MASH progression depends on the interaction between the gut microbiota, BA metabolism, and inflammatory responses in the livers of iHFC#2-fed C57BL/6 mice., (© 2024 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)

In the filamentous fungus Aspergillus oryzae, large amounts of amylolytic enzymes are inducibly produced by isomaltose, which is converted from maltose incorporated via the maltose transporter MalP. In contrast, the preferred sugar glucose strongly represses the expression of both amylolytic and malP genes through carbon catabolite repression. Simultaneously, the addition of glucose triggers the endocytic degradation of MalP on the plasma membrane. In budding yeast, the signal-dependent ubiquitin modification of plasma membrane transporters leads to selective endocytosis into the vacuole for degradation. In addition, during glucose-induced MalP degradation, the homologous of E6AP C-terminus-type E3 ubiquitin ligase (HulA) is responsible for the ubiquitin modification of MalP, and the arrestin-like protein CreD is required for HulA targeting. Although CreD-mediated MalP internalization occurs in response to glucose, the mechanism by which CreD regulates HulA-dependent MalP ubiquitination remains unclear. In this study, we demonstrated that three (P/L)PxY motifs present in the CreD protein are essential for functioning as HulA adaptors so that HulA can recognize MalP in response to glucose stimulation, enabling MalP internalization. Furthermore, four lysine residues (three highly conserved among Aspergillus species and yeast and one conserved among Aspergillus species) of CreD were found to be necessary for its ubiquitination, resulting in efficient glucose-induced MalP endocytosis. The results of this study pave the way for elucidating the regulatory mechanism of MalP endocytic degradation through ubiquitination by the HulA-CreD complex at the molecular level., 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 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To develop a training program for bronchial sleeve reconstruction using our previously developed 3-dimensional (3D) operable airway model and evaluate its effectiveness in surgical trainees., Methods: Eight trainees and 4 faculty surgeons were enrolled. Their right upper lobe sleeve reconstruction procedures were scored by 2 senior surgeons in a blinded fashion on a 5-point Likert scale on the following: airway wall tear, reapplied ligatures, reapplied needles, needle entry and exit, anastomotic bite, and caliber adjustment (full score: 30). The trainees were randomized into training and control groups (n = 4 in each group). The training group underwent 6 cycles of training guided by video-based instructions. The control group underwent regular clinical training. All trainees were reevaluated., Results: Before training, the median score of faculty surgeons was better than that of trainees (27.0 [range, 21.0-28.0] vs 17.5 [range, 9.5, 26.5]; P  = .05), suggesting the validity of the scoring method. The initial scores and anastomosis times were similar in the control and training groups. After training, the scores tended to be higher in the training than in the control group (median, 28.2 [range, 27.0-29.0] vs 20.8 [range, 15.0-28.0]; P  = .11). The anastomosis time tended to be shorter in the training group (median, 20.0 [18.9, 21.6] minutes vs 24.6 [range 17.8-30.9] minutes; P  = .69). The reduction in anastomosis time was significantly greater in the training group (median, -9.4 [range, -4.5 to -13.1] vs 0.0 [range, 5.3 to -6.0]; P  = .05)., Conclusions: The training program for bronchial sleeve resection using 3D airway models with video-based instructions improved the trainees' skills., Competing Interests: The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (© 2024 The Author(s).)

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.

Purpose: This study examined the immediate effects of oculomotor and bimanual coordination exercises, as well as a combination of the two, on stability of balance in athletes., Patients and Methods: Changes in center-of-gravity sway were measured in 30 college student athletes before and after the following three exercise conditions: 1) oculomotor exercises, 2) bimanual coordination exercises, and 3) a combination of oculomotor and bimanual coordination exercises (1+2). The order of these exercises was counterbalanced., Results: The combination of exercises (condition 3) reduced large swaying during balancing and immediately increased postural stability. Moreover, the oculomotor and bimanual coordination exercises (conditions 1 and 2) immediately reduced large sway during balancing when performed independently. Thus, the present study revealed that the combination of oculomotor and bimanual coordination exercises immediately reduced accidental swaying during balancing and also improved postural stability., Conclusion: This combination could be effective as an immediate balance adjustment method for athletes., Competing Interests: The authors have no conflicts of interest directly relevant to the content of this article., (© 2024 Matsuura et al.)

Background: Tsumura-Suzuki non-obese (TSNO) mice exhibit a severe form of metabolic dysfunction-associated steatohepatitis (MASH) with advanced liver fibrosis upon feeding a high-fat/cholesterol/cholate-based (iHFC) diet. Another ddY strain, Tsumura-Suzuki diabetes obese (TSOD) mice, are impaired in the progression of iHFC diet-induced MASH., Aim: To elucidate the underlying mechanisms contributing to the differences in MASH progression between TSNO and TSOD mice., Methods: We analyzed differences in the immune system, gut microbiota, and bile acid metabolism in TSNO and TSOD mice fed with a normal diet (ND) or an iHFC diet., Results: TSOD mice had more anti-inflammatory macrophages in the liver than TSNO mice under ND feeding, and were impaired in the iHFC diet-induced accumulation of fibrosis-associated macrophages and formation of histological hepatic crown-like structures in the liver. The gut microbiota of TSOD mice also exhibited a distinct community composition with lower diversity and higher abundance of Akkermansia muciniphila compared with that in TSNO mice. Finally, TSOD mice had lower levels of bile acids linked to intestinal barrier disruption under iHFC feeding., Conclusions: The dynamics of liver macrophage subsets, and the compositions of the gut microbiota and bile acids at steady state and post-onset of MASH, had major impacts on MASH development., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

In this era of endoscopic surgery, feedback from recorded surgical videos is useful and efficient; therefore, effective methods of obtaining this feedback are needed. We analyzed surgical videos using motion analysis software and verified the usefulness of visualizing and objectively evaluating surgical procedures. We measured the grasping and traction angles of the vascular sheath when using forceps and the trajectory of the forceps tip for the upper pulmonary vein during right upper lobectomy during video-assisted thoracoscopic surgery performed by three trainers and trainees. Compared with the trainers, the trainees exhibited insufficient traction of the vascular sheath, performed many slow and unnecessary manipulations, and sometimes performed sudden and fast movements. By visualizing the surgical procedures, the trainee will be better able to identify dangerous or futile movements. It may also make it easier to objectively recognize improvements in one's technique. Motion analysis software could allow for efficient surgical education and self-learning., (© 2024 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

The interosseous membrane (IOM) of the forearm plays a crucial role in facilitating forearm function and mechanical load transmission between the radius and ulna. Accurate characterization of its biomechanical properties is essential for developing realistic finite element models of the forearm. This study aimed to investigate the mechanical behavior and material properties of the central fibrous regions of the IOM using fresh frozen cadavers. Ten forearms from five cadavers were dissected, preserving the IOM and identifying the distal accessory band (DAB), central band (CB), and proximal accessory band (PAB). Bone-ligament-bone specimens were prepared and subjected to uniaxial tensile testing, with the loading direction aligned with the fiber orientation. Force-displacement curves were obtained and converted to force-strain and stress-strain curves using premeasured fiber lengths and cross-sectional areas. The results demonstrated distinct mechanical responses among the IOM regions, with the PAB exhibiting significantly lower force-strain behavior compared to the DAB and CB. The derived force-strain and stress-strain relationships provide valuable insights into the regional variations in stiffness and strength of the IOM, highlighting the importance of considering these differences when modeling the IOM in finite element analysis. In conclusion, this study establishes a foundation for the development of advanced finite element models of the forearm that accurately capture the biomechanical behavior of the IOM., 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 Ltd. All rights reserved.)

Thrombocytopenia is a common hematological complication of systemic lupus erythematosus (SLE). However, severe thrombocytopenia is a relatively rare presentation, accounting for only 3-10% of cases. A 52-year-old woman was being treated with 4 mg/day of prednisolone for 12 years for SLE-induced autoimmune hemolytic anemia. She presented to her family physician with nasal bleeding and purpura, which required more than two hours to control. She had bruises on her legs and mild multiple arthralgia. The platelet count was 19,000/µL. She was suspected to have developed immune thrombocytopenia as an exacerbation of SLE. Thus, she was referred to our hospital. Laboratory examination revealed thrombocytopenia, hypocomplementemia, and a positive result for anti-cardiolipin (CL) and anti-β 2 -glycoprotein (GP) I IgG antibodies. The patient was diagnosed with thrombocytopenic purpura, complicated by SLE. Methylprednisolone pulse therapy, followed by 60 mg/day of prednisolone and 200/400 mg of hydroxychloroquine on alternate days, was initiated. The platelet count increased from 5,000/µl to 50,000/µl, and the immature platelet fraction (IPF) decreased from 14.9% to 6.3%. Anti-CL and anti-β 2 -GPI IgG antibodies were considered to be associated with thrombocytopenia and a risk of thrombotic events after normalization of her platelet counts. Therefore, aspirin therapy was initiated to prevent thrombosis. As an episode of acute thrombocytopenia occurred without other clinical findings indicating active SLE, it was important to determine the exact cause of thrombocytopenia in this situation. Immediate recovery of thrombocytopenia with high-dose prednisolone reduced the risk of bleeding that could have otherwise been fatal., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Matsuura et al.)

Context: The coherent electron/spin transport in azurin, a species of copper protein, was calculated based on the Landauer model. The research is motivated by the fast electron transport and spin selectivity/polarization in azurin, which have been reported in relation to the chiral-induced spin selectivity of the peptide structure. The calculated spin polarization of copper proteins was large. This phenomenon was strongly influenced by the spin density of the atoms in the ligand group, whereas the contribution of copper was negligible. The results suggest that spin polarization in copper proteins is enhanced by that of the ligand groups. The predicted spin polarization aligns primarily with the scanning tunneling microscope-based break-junction technique to study the electronic properties of single-molecule junctions., Methods: Computational techniques employed in this study are nonequilibrium Green's functions (NEGF) and density functional theory (DFT) based on the Landauer model, implemented using the QuantumATK software (Synopsys Inc.). The Perdew-Burke-Ernzerhof (PBE) exchange-correlation functional was adopted for spin-polarized generalized gradient approximation (SGGA). The valence atomic orbitals were constructed using the wavefunctions of the SIESTA package, which was based on the norm-conserving Troullier-Martins relativistic pseudopotentials for describing core electrons. The mesh used for real-space integration was 150 Ha., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Subunit vaccines are among the most useful vaccine modalities; however, their low immunogenicity necessitates the addition of adjuvants. Although adjuvants improve immune responses induced by vaccines, they often cause adverse reactions. To address this, we developed an adjuvant-free subunit vaccine platform that uses pre-existing antibodies generated from past infections or vaccinations as carriers for the delivery of vaccine antigens. Although we have confirmed the usefulness of this platform for nasal vaccines, its suitability as a parenterally injectable vaccine remains uncertain. Here, we verified the potential of our vaccine platform to harness pre-existing immunity for parenterally injectable vaccines. We generated RBD-HA by combining the receptor binding domain (RBD) derived from SARS-CoV-2 as a vaccine antigen with hemagglutinin (HA) sourced from influenza viruses to serve as the carrier protein. We revealed that subcutaneous vaccination with RBD-HA effectively triggered strong RBD-specific IgG responses in mice previously infected with the influenza A virus, even in the absence of adjuvants, and conferred protection to mice against SARS-CoV-2 upon challenge. Furthermore, we revealed that vaccination with RBD-HA did not induce an inflammatory response, such as inflammatory cytokine production, swelling, and recruitment of inflammatory immune cells, whereas conventional vaccines combined with adjuvants induced these adverse reactions. In addition, we demonstrated the remarkable versatility of this platform using a vaccine antigen derived from Streptococcus pneumoniae. These findings indicate the potential of this adjuvant-free vaccine platform to enhance the efficacy of parenterally injectable subunit vaccines and reduce adverse reactions., Competing Interests: Declaration of competing interest Y.Y. has filed a patent application relating to the contents of this manuscript. N.T. and Y.Y. are employees of the Research Foundation for Microbial Diseases at Osaka University. The other authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Coronavirus disease 2019 (COVID-19) induces respiratory dysfunction as well as kidney injury. Although the kidney is considered a target organ of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and affected by the COVID-19-induced cytokine storm, the mechanisms of renal reaction in SARS-CoV-2 infection are unknown. In this study, a murine COVID-19 model was induced by nasal infection with mouse-adapted SARS-CoV-2 (MA10). MA10 infection induced body weight loss along with lung inflammation in mice 4 days after infection. Serum creatinine levels and the urinary albumin/creatinine ratio increased on day 4 after MA10 infection. Measurement of the urinary neutrophil gelatinase-associated lipocalin/creatinine ratio and hematoxylin and eosin staining revealed tubular damage in MA10-infected murine kidneys, indicating kidney injury in the murine COVID-19 model. Interferon (IFN)-γ and interleukin-6 upregulation in the sera of MA10-infected mice, along with the absence of MA10 in the kidneys, implied that the kidneys were affected by the MA10 infection-induced cytokine storm rather than by direct MA10 infection of the kidneys. RNA-sequencing analysis revealed that antiviral genes, such as the IFN/Janus kinase (JAK) pathway, were upregulated in MA10-infected kidneys. Upon administration of the JAK inhibitor baricitinib on days 1 - 3 after MA10 infection, an antiviral pathway was suppressed, and MA10 was detected more frequently in the kidneys. Notably, JAK inhibition upregulated the hypoxia response and exaggerated kidney injury. These results suggest that endogenous antiviral activity protects against SARS-CoV-2-induced kidney injury in the early phase of infection, providing valuable insights into the pathogenesis of COVID-19-associated nephropathy. NEW & NOTEWORTHY Patients frequently present with acute kidney injury or abnormal urinary findings after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we investigated how the kidneys respond during SARS-CoV-2 infection using a murine coronavirus disease 2019 (COVID-19) model and showed that Janus kinase-mediated endogenous antiviral activity protects against kidney injury in the early phase of SARS-CoV-2 infection. These findings provide valuable insights into the renal pathophysiology of COVID-19.

The relationship of histopathological changes and the infection of Piscine orthoreovirus 2 (PRV-2) was investigated in coho salmon that were suffering from the erythrocytic inclusion body syndrome (EIBS). Immunohistochemical observations revealed abundant σ1 protein of PRV-2 in the spongy layer of the ventricle of the heart, where severe myocarditis was observed. In the spleen, the virus protein was detected in many erythrocytes, some of which were spherical-shaped and apparently dead. The number of erythrocytes was decreased in the spleen compared to the apparently healthy fish. The virus protein was also detected in some erythrocytes in blood vessels. The viral protein was often detected in many macrophages ingesting erythrocytes or dead cell debris in the spleen or in the kidney sinusoids. Large amounts of the viral genomic segment L2 were also detected in these organs by RT-qPCR. Many necrotic foci were found in the liver, although the virus protein was not detected in the hepatocytes. These results suggest that the primary targets of PRV-2 are myocardial cells and erythrocytes and that clinical symptoms such as anaemia or jaundice and histopathological changes such as myocarditis in EIBS-affected coho salmon are caused by PRV-2 infection., (© 2024 John Wiley & Sons Ltd.)

Purpose: The purpose of this study was to estimate the bone strength after plate removal over time and to investigate the progression of bone strength recovery., Methods: A consecutive series of 31 patients was investigated to evaluate bone strength before and after forearm plate removal. Patients who were included underwent plate fixation for forearm diaphyseal fractures and were scheduled for plate removal. Computed tomography (CT) scans of the entire length of the bilateral forearms were taken before plate removal and at 1, 3, and 6 months after surgery. Patient-specific CT-based finite element analysis was used to predict the forearm bone fracture strength against an axial load (N), defined as the bone strength. Bone strength was estimated by patient-specific CT-based finite element analysis at each time point., Results: The mean age of the patients was 40.4 years. The mean time between plate fixation and removal was 27.5 months. Bone strength before the removal was estimated as reduced to 47% of that of the uninjured side. This was constant regardless of age group, involvement of the radius or ulna, Arbeitsgemeinschaft für Osteosynthesefragen (AO) classification, open fracture, or type of plate. Bone strength at 1, 3, and 6 months after removal was estimated to be 66%, 85%, and 97%, respectively. The bone strength of the distal ulna was weaker than that at the other sites in the forearm and showed delayed recovery., Conclusions: Bone strength after plate removal showed recovery within 3-6 months and was fully recovered by 6 months. The degree of recovery of bone atrophy varies from site to site, and patients should be careful about refracture after removal., Clinical Relevance: Clinicians should be aware that bone strength may not be sufficiently restored even 6 months after plate removal of forearm fractures., (Copyright © 2024 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Background: In early-stage non-small cell lung cancer (NSCLC), the presence of a ground-glass opacity (GGO) component in the primary lesion on high-resolution computed tomography (CT) is recognized as a favorable prognostic factor. Even in NSCLC with a GGO component, lymph node metastases are occasionally detected during or after surgery. However, the prognostic impact of GGO components in these patients has not been clarified. We aimed to examine the prognostic significance of GGO components as radiological findings of primary lesions of completely resected NSCLC with pathological nodal involvement., Methods: This study included 290 patients (11%) with pathological nodal involvement among 2,546 patients who underwent complete resection of NSCLC at our institution. Patients with an unknown primary lesion (T0) or centrally located lung cancer were excluded. The 290 patients were divided into two groups [i.e., the part-solid ("PS") and "Solid" groups] according to the radiological findings of the primary lesion, and their clinicopathological characteristics and prognoses were compared. Furthermore, a multivariate analysis was performed using the Cox proportional hazards model to examine the factors affecting the overall survival (OS)., Results: The OS in the PS group (n=58) was significantly longer than that in the Solid group (n=232; P=0.039). However, multivariate analysis only revealed age [hazard ratio (HR) =1.77; 95% confidence interval (CI): 1.15-2.72] and the clinical T factor (HR =1.58; 95% CI: 1.01-2.47), but not the radiological findings of primary lesions, as the independent prognostic factors. Furthermore, the OS did not differ significantly between the PS and Solid groups matched for the clinical T and N factors (n=58 patients each)., Conclusions: GGO components in the primary lesion, considered a decisive prognostic factor in early-stage NSCLC, did not affect the prognosis of patients with NSCLC and pathological nodal involvement., 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-24-144/coif). The authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Citrobacter koseri causes opportunistic infections in various organs. We herein report an 84-year-old man with diabetes mellitus who presented to our hospital with left hip pain and walking difficulty. Computed tomography showed an extensive abscess with gas production, mainly in the left retroperitoneal space, caused by C. koseri infection. Despite daily cleaning of the wound and antimicrobial therapy (with surgical drainage), the patient developed repeated pneumonia and small bowel hemorrhaging caused by disseminated intravascular coagulation and died on day 65 of hospitalization. Overall, retroperitoneal abscesses caused by C. koseri are rare, and multiple abscesses may show a poor prognosis.

Novel respiratory viruses can cause a pandemic and then evolve to coexist with humans. The Omicron strain of severe acute respiratory syndrome coronavirus 2 has spread worldwide since its emergence in late 2021, and its sub-lineages are now established in human society. Compared to previous strains, Omicron is markedly less invasive in the lungs and causes less severe disease. One reason for this is that humans are acquiring immunity through previous infection and vaccination, but the nature of the virus itself is also changing. Using our newly established low-volume inoculation system, which reflects natural human infection, we show that the Omicron strain spreads less efficiently into the lungs of hamsters compared with an earlier Wuhan strain. Furthermore, by characterizing chimeric viruses with the Omicron gene in the Wuhan strain genetic background and vice versa , we found that viral genes downstream of ORF3a, but not the S gene, were responsible for the limited spread of the Omicron strain in the lower airways of the virus-infected hamsters. Moreover, molecular evolutionary analysis of SARS-CoV-2 revealed a positive selection of genes downstream of ORF3a (M and E genes). Our findings provide insight into the adaptive evolution of the virus in humans during the pandemic convergence phase.IMPORTANCEThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has spread worldwide since its emergence in late 2021, and its sub-lineages are established in human society. Compared to previous strains, the Omicron strain is less invasive in the lower respiratory tract, including the lungs, and causes less severe disease; however, the mechanistic basis for its restricted replication in the lower airways is poorly understood. In this study, using a newly established low-volume inoculation system that reflects natural human infection, we demonstrated that the Omicron strain spreads less efficiently into the lungs of hamsters compared with an earlier Wuhan strain and found that viral genes downstream of ORF3a are responsible for replication restriction in the lower respiratory tract of Omicron-infected hamsters. Furthermore, we detected a positive selection of genes downstream of ORF3a (especially the M and E genes) in SARS-CoV-2, suggesting that these genes may undergo adaptive changes in humans., Competing Interests: The authors declare no conflict of interest.

Objective: Dyslexia is characterized by difficulties with fluent word recognition, decoding, or spelling, and it has been linked to family history. Given the impact of dyslexia on broad academic activities and well-being, ensuring that information about dyslexia is accessible to affected children and their families is vital. This study aims to assess the readability levels of dyslexia-related websites, with the hypothesis that such websites should be written at an appropriate readability level to accommodate those who may also have reading challenges., Methods: This study analyzes the readability of 50 web articles on dyslexia using 6 readability formulas: Flesch-Kincaid Reading Ease, Flesch-Kincaid Grade Level, Gunning Fog Score, Simple Measure of Gobbledygook (SMOG) Index, Coleman Liau Index, and Automated Readability Index. The search term "What is dyslexia" was used on Google. Each article was analyzed using the online calculation website WebFX. The readability goal for these websites was set at fifth grade, a level recommended for patients with reading challenges., Results: The study found that among the 50 websites, the lowest median readability score was 11.8 (corresponding to a 12th-grade level) on the SMOG Index, while the highest scores were 15.5 on both the Gunning Fog Score and the Coleman Liau Index (indicative of college-level readability). Almost none of the websites had scores below a fifth-grade level., Conclusion: Most websites related to dyslexia are too complex. Tools such as readability metrics and sentence restructuring by AI can help make the information more accessible and understandable to the stakeholders., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

2,5-Disubstituted furans are frequently found in pharmaceuticals and bioactive natural products. Nucleophilic substitution reactions on the carbon atom adjacent to the furan ring are useful for producing various furan derivatives. However, the formation of 5-substituted 2-halomethylfuran and the subsequent nucleophilic substitution reactions are often limited by severe undesired reactions caused by the highly reactive halomethylfurans. This paper reports the successful rapid synthesis of various 2,5-disubstituted furans using microflow technology, which suppresses undesired reactions including dimerization and ring opening of the furans. We observed that Brønsted acids had a significant effect on the nucleophilic substitution reaction and the use of HBr and HI gave the best results. A plausible mechanism of the Brønsted acid-mediated nucleophilic substitutions in the developed approach was proposed.

Purpose: Pulvertaft tendon repair is a strong suture technique; however, proper tendon tension is impaired by repair site elongation. Therefore, methods to reduce postoperative elongation are warranted. This study aimed to determine the effects of additional core sutures during Pulvertaft tendon repair on repair site elongation and rupture strength., Methods: A total of 48 finger extensor tendons were harvested from fresh-frozen cadavers, and tendons with similar diameters were paired. The 24 pairs of tendons were divided into the following 4 groups: group I, 3 interlaced weaves only; group II, 3 interlaced weaves and 2 core suture strands with 4-0 nylon; group III, 3 interlaced weaves and 2 core suture strands with 4-0 FiberWire; and group IV, 4 interlaced weaves only. Each sutured tendon was placed in a Universal Testing Machine, and repair site elongation after repeated traction loads and rupture strength were measured., Results: The mean elongation values were 2.74 ± 0.84 mm, 1.80 ± 0.16 mm, 1.60 ± 0.18 mm, and 1.92 ± 0.18 mm for groups I, II, III, and IV, respectively. The elongation values were significantly lower in groups II, III, and IV than in group I. The mean rupture strengths were 64.9 ± 16.0 N, 94.8 ± 17.2 N, 110.9 ± 21.3 N, and 104.9 ± 17.5 N for groups I, II, III, and IV, respectively. Rupture strengths were significantly higher for groups III and IV than for group I., Conclusions: After adding core sutures during Pulvertaft tendon repair, the elongation amount decreased, and the rupture strength improved., Clinical Relevance: The study showed the effect of additional core sutures during Pulvertaft tendon repair, suggesting that it could be useful in reducing postoperative tendon elongation when extensor tendon transfers are performed., (Copyright © 2024 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)