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This case report shows unique aneurysm at the left ventricular apex associated with a double-chambered left ventricle (DCLV) in asymptomatic 69-year-old female. The aneurysm was located at the apex of an accessory chamber, which was formed by hypertrophied muscle band and the interventricular septum, along with a pronounced jet flow directed towards the apex aneurysm. These finding suggests that the obstruction at the base of the accessory chamber caused a pressure overload at the apex, ultimately leading to the development of the aneurysm. To best of our knowledge, this is the first case to prove the underlying cause of aneurysm formation in DCLV., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Objectives: Cement penetration (CP) plays a key role in implant stability for cemented total knee arthroplasty (TKA), and the radiolucent line (RLL) >2 ​mm is a preliminary sign for loosening of components. However, the direct relationship between CP and the frequency of RLL >2 ​mm is unclear, and the best cut-off value for CP to prevent RLL >2 ​mm also remains unclear. This study aimed to investigate this relationship between CP and RLL and to determine the clinical cut-off value for tibial CP in patients 2 years after TKA., Methods: This retrospective study investigated 157 knees from 123 patients with osteoarthritis who underwent cemented TKA. The CP and RLL immediately after TKA and the RLL 2 years after TKA were measured for the medial, lateral, anterior, and posterior tibial baseplate zones. Receiver operating characteristic (ROC) curves were constructed to determine the best cut-off values for CP., Results: RLL >2 ​mm was not observed just after TKA. An RLL >2 ​mm was observed in any tibial baseplate zone in 22 knees from 20 patients (RLL+ group) and was not observed in the remaining (RLL- group) 2 years after TKA. The mean CP for all zones was significantly higher in the RLL- group (2.5 ​± ​1.1 ​mm) than in the RLL+ group (1.7 ​± ​0.6 ​mm; P ​< ​0.001). An RLL >2 ​mm was seen in 21 knees in the medial zone, 9 knees in the lateral zone, 8 knees in the anterior zone, and 3 knees in the posterior zone. CP values with RLL >2 ​mm were significantly lower than those without the RLL at the medial, anterior, and posterior tibial baseplate zones. The best cut-off values from the ROC curve of CP in each zone were between 1.1 ​mm and 2.1 ​mm., Conclusions: The depth of the CP directly affects the incidence of an RLL >2 ​mm. The best cut-off value for tibial CP to prevent an RLL >2 ​mm is 2.1 ​mm., 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 Authors. Published by Elsevier Inc. All rights reserved.)

Background: Few studies have compared the clinical outcomes of patients with pelvic bone sarcomas treated surgically and those treated with particle beam therapy. This is a multicenter retrospective cohort study which compared the clinical outcomes of patients with pelvic bone sarcoma who underwent surgical treatment and particle beam therapy in Japan., Methods: A total of 116 patients with pelvic bone sarcoma treated at 19 specialized sarcoma centers in Japan were included in this study. Fifty-seven patients underwent surgery (surgery group), and 59 patients underwent particle beam therapy (particle beam group; carbon-ion radiotherapy: 55 patients, proton: four patients)., Results: The median age at primary tumor diagnosis was 52 years in the surgery group and 66 years in the particle beam group (P < 0.001), and the median tumor size was 9 cm in the surgery group and 8 cm in the particle beam group (P = 0.091). Overall survival (OS), local control (LC), and metastasis-free survival (MFS) rates were evaluated using the Kaplan-Meier method and compared among 116 patients with bone sarcoma (surgery group, 57 patients; particle beam group, 59 patients). After propensity score matching, the 3-year OS, LC, and MFS rates were 82.9% (95% confidence interval [CI], 60.5-93.2%), 66.0% (95% CI, 43.3-81.3%), and 78.4% (95% CI, 55.5-90.5%), respectively, in the surgery group and 64.9% (95% CI, 41.7-80.8%), 86.4% (95% CI, 63.3-95.4%), and 62.6% (95% CI, 38.5-79.4%), respectively, in the particle beam group. In chordoma patients, only surgery was significantly correlated with worse LC in the univariate analysis., Conclusions: The groups had no significant differences in the OS, LC, and MFS rates. Among the patients with chordomas, the 3-year LC rate in the particle beam group was significantly higher than in the surgery group., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Objectives: To propose a nomogram-based survival prediction model for esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy using pretreatment computed tomography (CT), positron emission tomography (PET) radiomics and dosiomics features, and common clinical factors., Methods: Radiomics and dosiomics features were extracted from CT and PET images and dose distribution from 2 institutions. The least absolute shrinkage and selection operator (LASSO) with logistic regression was used to select radiomics and dosiomics features by calculating the radiomics and dosiomics scores (Rad-score and Dos-score), respectively, in the training model. The model was trained in 81 patients and validated in 35 patients at Center 1 using 10-fold cross validation. The model was externally tested in 26 patients at Center 2. The predictive clinical factors, Rad-score, and Dos-score were identified to develop a nomogram model., Results: Using LASSO Cox regression, 13, 11, and 19 CT, PET-based radiomics, and dosiomics features, respectively, were selected. The clinical factors T-stage, N-stage, and clinical stage were selected as significant prognostic factors by univariate Cox regression. In the external validation cohort, the C-index of the combined model of CT-based radiomics, PET-based radiomics, and dosiomics features with clinical factors were 0.74, 0.82, and 0.92, respectively. Significant differences in overall survival (OS) in the combined model of CT-based radiomics, PET-based radiomics, and dosiomics features with clinical factors were observed between the high- and low-risk groups (P = 0.019, 0.038, and 0.014, respectively)., Conclusion: The dosiomics features have a better predicter for OS than CT- and PET-based radiomics features in ESCC treated with radiotherapy., Clinical Relevance Statement: The current study predicted the overall survival for esophageal squamous cell carcinoma patients treated with definitive chemoradiotherapy. The dosiomics features have a better predicter for overall survival than CT- and PET-based radiomics features., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: The tibial tubercle-to-trochlear groove (TT-TG) distance and Insall-Salvati (I/S) ratio are widely used to determine the need for distal realignment in conjunction with medial patellofemoral ligament (MPFL) reconstruction in patients with recurrent patellar dislocation. A TT-TG distance >20 mm and an I/S ratio >1.3 are significant anatomical risk factors for patellar instability. However, these parameters have traditionally been measured using non-weight-bearing (NWB) imaging modalities. As patellar dislocation occurs during weight-bearing actions, these two parameters should be measured under weight-bearing conditions. Thus, this study aimed to measure the TT-TG distance and I/S ratio using upright full-weight-bearing (FWB) computed tomography (CT) scans and compare the data with NWB CT scans., Methods: This study included 49 knee joints of 26 healthy volunteers. CT images were obtained under both FWB and NWB standing conditions using a 320-detector row upright CT scanner. TT-TGs in the axial plane and I/S ratios in the sagittal plane were measured and compared., Results: The average FWB TT-TG distance was 20.3 ± 3.9 mm, whereas the average NWB TT-TG distance was 12.3 ± 4.7 mm. The TT-TG level was significantly higher in the FWB condition than that in the NWB condition (P < 0.001). The I/S ratios were comparable between the FWB and NWB conditions (P = 0.29)., Conclusions: The TT-TG distance in the standing weight-bearing condition was larger than the conventional TT-TG distance and surpassed the historical cutoff value of TT-TG, which may affect the indication of additional distal realignment in MPFL reconstruction for patellar instability., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Masahiro Jinzaki has received a grant from Canon Medical Systems. However, Canon Medical Systems was not involved in the design and conduct of the study, in the collection, analysis, and interpretation of the data, or in the preparation, review, and approval of the manuscript. The remaining authors have no conflicts of interest to declare.]., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Severe trauma patients often require emergent interventions, such as massive transfusion, resuscitative procedures, and surgical procedures, and consume considerable human and medical resources. However, few practical indices can be easily used for emergent interventions. In recent years, it has become clear that rSIG (Reverse Shock Index multiplied by Glasgow Coma Scale [GCS] score), which can be easily calculated from vital signs, is a promising predictor of mortality. However, it is unclear whether rSIG is useful for emergent interventions., Methods: Data collected by the Japan Trauma Data Bank for adult patients admitted directly from the scene of trauma between April 2019 and December 2020 were analysed. The outcomes were massive transfusion, resuscitative procedures, surgical procedures and emergent interventions. Emergent interventions were defined as the composite outcome of massive transfusion, resuscitative procedures, and surgical procedures. The ability of rSIG to predict massive transfusion was compared with that of the ABC score and FASILA score by receiver-operating characteristic curve analysis. The ability of rSIG to predict resuscitative and surgical procedures was compared with that of the Shock Index (SI), GCS, Triage Revised Trauma score (T-RTS), and Previous Simple Prediction (PSP) score. The ability of rSIG to predict emergent interventions was compared with that of T-RTS, PSP, ABC, and FASILA. In addition to rSIG, rSIM (Reverse Shock Index multiplied by best motor response score) was also analysed as a supplement., Results: The study included 32,201 patients, 6,371 of whom required emergent interventions. The area under the receiver-operating characteristic curve (AUROC) for massive transfusion was highest for rSIG (0.846 [95 % confidence interval 0.832-0.859]) and significantly higher for rSIG than for rSIM, ABC and FASILA (all p < 0.0001). AUROCs for resuscitative and surgical procedures were highest for rSIG (0.777 [0.769-0.785] and 0.731 [0.720-0.741], respectively) and significantly higher than those for rSIM, SI, GCS, T-RTS, and PSP (all p < 0.0001). The AUROC for emergent interventions was highest for rSIG (0.760 [0.753-0.768]) and significantly higher for rSIG than for rSIM, T-RTS, PSP, ABC, or FASILA (all p < 0.0001)., Conclusions: rSIG is a simple and effective point-of-care predictor of emergent interventions during initial management of trauma., 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 study., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Two-dimensional (2D) coronal joint line orientation on radiography under weight-bearing conditions has been widely used in evaluating knee osteoarthritis (OA). However, the effects of tibial rotation remain unknown. The present study aimed to newly define three-dimensional (3D) joint surface orientation relative to the floor as an unchangeable 3D angle unaffected by tibial rotation using upright computed tomography (CT), and to investigate correlations between 3D and 2D parameters in knee OA., Methods: Sixty-six knees in 38 patients with varus knee OA underwent standing hip-to-ankle digital radiography and upright CT. The 2D parameters measured on radiographs included femorotibial angle (FTA), tibial joint line angle (TJLA), lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA), and joint line convergence angle (JLCA). The 3D inner product angle between vectors of the tibial joint surface and the floor from CT was defined as the 3D joint surface-floor angle., Results: Mean 3D joint surface-floor angle was 6.0 ± 3.6°. No correlation was identified between 3D joint surface-floor angle and 2D joint line parameters, even though FTA correlated substantially with 2D joint line parameters. No significant differences in 3D joint surface-floor angle were identified among Coronal Plane Alignment of the Knee (CPAK) types., Conclusions: The 3D joint surface orientation did not correlate with 2D coronal joint line orientation and was unaffected by CPAK classification types. This finding suggests that current 2D evaluations should be reconsidered for a better understanding of true knee joint line orientation., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Masahiro Jinzaki has received a grant from Canon Medical Systems. However, Canon Medical Systems was not involved in the design and conduct of the study, in the collection, analysis, and interpretation of the data, or in the preparation, review, and approval of the manuscript. The remaining authors have no conflicts of interest to declare.]., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: Repetitive paired-pulse transcranial magnetic stimulation (iTMS) at indirect (I) wave intervals increases motor-evoked potentials (MEPs) produced by transcranial magnetic stimulation (TMS) to primary motor cortex (M1). However, the effects of iTMS at early and late intervals on the plasticity of specific I-wave circuits remain unclear. This study therefore aimed to assess how the timing of iTMS influences intracortical excitability within early and late I-wave circuits. To investigate the cortical effects of iTMS more directly, changes due to the intervention were also assessed using combined TMS-electroencephalography (EEG)., Material and Methods: Eighteen young adults (aged 24.6 ± 4.2 years) participated in four sessions in which iTMS targeting early (1.5-millisecond interval; iTMS 1.5 ) or late (4.0-millisecond interval; iTMS 4.0 ) I-waves was applied over M1. Neuroplasticity was assessed using both posterior-to-anterior (PA) and anterior-to-posterior (AP) stimulus directions to record MEPs and TMS-evoked EEG potentials (TEPs) before and after iTMS. Short-interval intracortical facilitation (SICF) at interstimulus intervals of 1.5 and 4.0 milliseconds was also used to index I-wave activity., Results: MEP amplitude was increased after iTMS (p < 0.01), and this was greater for PA responses (p < 0.01) but not different between iTMS intervals (p = 0.9). Irrespective of iTMS interval and coil current, SICF was facilitated after the intervention (p < 0.01). Although the N45 produced by AP stimulation was decreased by iTMS 1.5 (p = 0.04), no other changes in TEP amplitude were observed., Conclusions: The timing of iTMS failed to influence which I-wave circuits were potentiated by the intervention. In contrast, decreases in the N45 suggest that the neuroplastic effects of iTMS may include disinhibition of intracortical inhibitory processes., (Copyright © 2022 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Objectives: Short-interval intracortical inhibition (SICI) is a paired-pulse transcranial magnetic stimulation (TMS) technique that is commonly used to quantify intracortical inhibitory tone in the primary motor cortex. Whereas conventional measures of SICI (C-SICI) quantify inhibition by the amplitude of the motor evoked potential (MEP), alternative measures involving threshold tracked SICI (TT-SICI) instead record the TMS intensity required to maintain a consistent MEP amplitude. Although both C-SICI and TT-SICI are thought to reflect inhibition mediated by γ-aminobutyric acid type A (GABA A ) receptors, recent evidence suggests that the mechanisms involved with each measure may not be equivalent. This study aimed to use combined TMS-electroencephalography (TMS-EEG) to investigate the cortical mechanisms contributing to C-SICI and TT-SICI., Materials and Methods: In 20 young adults (30.6 ± 8.1 years), C-SICI and TT-SICI were recorded with multiple conditioning intensities, using both posterior-to-anterior (PA) and anterior-to-posterior (AP) induced currents, and this was compared with the TMS-evoked EEG potential (TEP)., Results: We found no relationship between the magnitude of C-SICI and TT-SICI within each current direction. However, there was a positive relationship between the slope (derived from multiple conditioning intensities) of inhibition recorded with C-SICI and TT-SICI, but only with a PA current. Furthermore, irrespective of conditioning intensity or current direction, measures of C-SICI were unrelated to TEP amplitude. In contrast, TT-SICI was predicted by the P30 generated with AP stimulation., Conclusions: Our findings further demonstrate that C-SICI and TT-SICI likely reflect different facets of GABA A -mediated processes, with inhibition produced by TT-SICI appearing to align more closely with TMS-EEG measures of cortical excitability., (Copyright © 2021 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Background: The traditional anteroposterior (AP) axis (i.e., Akagi's line) has been widely used as the tibial component AP axis during total knee arthroplasty (TKA). However, this AP axis has been defined based on computed tomography (CT) in a non-weight-bearing supine position. In this study, AP axes of the tibial plateau from upright CT in weight-bearing and non-weight-bearing positions were determined and compared., Methods: This study included 43 knees from 23 healthy volunteers. CT images were obtained in weight-bearing and non-weight-bearing standing positions using a 320-detector row upright CT scanner. The line perpendicular to surgical transepicondylar axis projected onto the tibia plateau was determined as the AP axis in upright weight-bearing and non-weight-bearing conditions. Angular differences between these two conditions were measured., Results: The upright weight-bearing AP axis was positioned in a mean of 7.4 ± 4.3° of internal rotation relative to the traditional AP axis. Distance between the traditional and upright weight-bearing AP axis was 2.9 ± 1.6 mm at the edge of the tibial plateau. The upright non-weight-bearing AP axis was positioned in a mean of 3.5 ± 4.1° of internal rotation relative to the traditional AP axis. Mean angular difference between weight-bearing and non-weight-bearing conditions was 3.9 ± 4.1°., Conclusions: The upright weight-bearing AP axis was positioned in 7.4° of internal rotation relative to the traditional AP axis, showing one-seventh of the tibial tuberosity away from the medial border of the tibial tubercle, which represents a practical landmark for the tibial component AP axis during TKA., 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 © 2022. Published by Elsevier B.V.)

Antibody-conjugated nanoparticles are used in a fields ranging from medicine to engineering. NanoAct® nanobeads are cellulose nanoparticles used in lateral flow assays that are highly water dispersible. In order to promote the adsorption of antibodies onto NanoAct® particles while maintaining their activity, we analyzed the adsorption onto NanoAct® particles thermodynamically and elucidated the adsorption mechanism. In an immunochromatographic assay, the amount of adsorbed antibody and the color intensity of the test line increased as the pH decreased. The zeta potential of the nanoparticles remained constant at around -30 mV over the pH range from 2 to 10. The model antibody had pI values between 6.2 and 6.8. Isothermal calorimetry analysis showed that adsorption of antibody to the NanoAct® particle is an endothermic reaction under low pH conditions, an exothermic reaction between pH 6 and pH 7, and a weakly exothermic reaction above pH 7. These data indicate that the changes in net charge of the antibody surface as a function of pH influence the pH dependence of antibody adsorption to the negatively charged NanoAct®. This suggests that increased positive charge on the antibody surface will result in a more sensitive NanoAct®-based immunoassay., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Due to an increasing number of dementia patients, the development of a rapid and sensitive method for cognitive assessment is awaited. Here, we examined the usefulness of a novel and short (3 min) eye tracking device to evaluate the cognitive function of normal control (NC, n = 52), mild cognitive impairment (MCI, n = 52), and Alzheimer's disease (AD, n = 70) subjects. Eye tracking total score declined significantly in MCI (**p < 0.01 vs NC) and AD (**p < 0.01 vs NC, ## p < 0.01 vs MCI), and correlated well with the mini-mental state examination (MMSE) score (r = 0.57, *p < 0.05). Furthermore, the eye tracking test, especially memory and deductive reasoning tasks, effectively discriminated NC, MCI and AD. The present novel eye tracking test clearly discriminated cognitive functions among NC, MCI, and AD subjects, thereby providing an advantage for the early detection of MCI and AD in screening., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Most of the currently used prognostic models for COVID-19 are based on Western cohorts, but it is unknown whether any are applicable to patients with COVID-19 in Japan., Methods: This retrospective cohort study included 160 patients with COVID-19 who were admitted to the National Center for Global Health and Medicine between January 26, 2020 and July 25, 2020. We searched PubMed for prognostic models for COVID-19. The predicted outcome was initiation of respiratory support or death. Performance of the candidate models was evaluated according to discrimination and calibration. We recalibrated the intercept of each model with our data. We also updated each model by adding β2-microglobulin (β2MG) to the model and recalculating the intercept and the coefficient of β2MG., Results: Mean patient age was 49.8 years, 68% were male, 88.7% were Japanese. The study outcomes occurred in 15 patients, including two deaths. Two-hundred sixty-nine papers were screened, and four candidate prognostic models were assessed. The model of Bartoletti et al. had the highest area under receiver operating characteristic curve (AUC) (0.88; 95% confidence interval 0.81-0.96). All four models overestimated the probability of occurrence of the outcome. None of the four models showed statistically significant improvement in AUCs by adding β2MG., Conclusions: Our results suggest that the existing prediction models for COVID-19 overestimate the probability of occurrence of unfavorable outcomes in a Japanese cohort. When applying a prediction model to a different cohort, it is desirable to evaluate its performance according to the prevalent health situation in that region., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Cu-diacetyl-bis (N4-methylthiosemicarbazone) (CuATSM) has both anti-oxidative and anti-inflammatory activities, but its therapeutic efficacy for oxidative stress has not been thoroughly investigated in acute ischemic stroke. Here, the present study was designed to assess the efficacies of CuATSM in acute ischemic stroke by comparing with the standard neuroprotective reagent edaravone. Mice were subjected to transient middle cerebral occlusion (tMCAO) for 60 min, and then intravenously administrated with CuATSM (1.5 mg/kg) or edaravone (3 mg/kg) just after the reperfusion, and examined at 1 and 3 d. Compared with the vehicle group, CuATSM treatment decreased infarct volumes and oxidative stress at 3d after tMCAO, which was further enhanced by combined CuATSM + edaravone treatment as compared with single CuATSM group, but not improve neurobehaviors. The present study demonstrated that CuATSM showed strong antioxidative and neuroprotective effects in acute ischemic stroke, which was enhanced by the combination with edaravone., Competing Interests: Declaration of Competing Interest The authors disclose no potential conflict of interests., (Copyright © 2020 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.)

Background & Aims: Chronic liver diseases, including hepatocellular carcinoma (HCC), lead to an imbalance in energy metabolism. The non-protein respiratory quotient (npRQ), which estimates energy malnutrition, can be evaluated using an indirect calorimeter; however, npRQ measurement is limited in routine work. This study aimed to investigate the relationship between the albumin-bilirubin (ALBI) score and npRQ in patients with HCC., Methods: We conducted a retrospective cohort study in 109 patients with HCC who underwent indirect calorimetry and then compared the npRQ with various clinical parameters, including liver function and tumor factors., Results: The median npRQ was 0.82. A significant negative correlation was found between the npRQ and the ALBI score (r = -0.35, p < 0.001). The median npRQ in modified ALBI (mALBI) grades 1, 2a, 2b, and 3 were 0.84, 0.86, 0.81, and 0.79, respectively (grade 2a vs. 2b, p = 0.002). Factors associated with npRQ <0.85, which is reported to be the best cutoff value for energy malnutrition, were analyzed. On multivariate analysis, the ALBI score (cutoff value, -2.18) was the only significant independent factor (odds ratio, 7.65; p < 0.001). The proportion of HCC patients with npRQ <0.85 significantly increased among patients with an ALBI score ≥-2.18 (45/51, 88.2%) compared with those with an ALBI score <-2.18 (29/58, 50%) (p < 0.001)., Conclusions: The ALBI score might be a useful predictor for energy malnutrition in patients with HCC. In addition, most HCC patients with mALBI grade 2b or 3 can be considered to have energy malnutrition., Competing Interests: Conflict of interest The authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Skeletal related events due to metastatic bone tumors markedly affect the activities of daily living (ADL) and quality of life (QOL) in cancer patients. We focused on multidisciplinary therapy for metastatic bone tumors. This study aimed to evaluate the outcomes of surgical treatment for metastatic bone tumors in the extremities., Methods: We retrospectively reviewed 114 patients who underwent surgical treatment for metastatic bone tumors of the extremities between 2008 and 2019 and 69 patients were reassessed for more than 6 months after surgery. The most common primary tumor was renal, followed by lung, thyroid, and breast cancers. We assessed 69 patients' performance status (PS), Barthel Index (BI) for ADL, EuroQol 5 Dimensions (EQ-5D) for QOL, and numerical rating scale (NRS) for pain and analyzed these postoperative values relative to preoperative values using Friedman's test. The postoperative overall survival and the prognostic factors were evaluated using the Kaplan-Meier method, the log-rank test and Cox proportional hazards analysis., Results: The 1-year overall survival rate was 59%, and the median survival time after surgery was 20 months. Primary tumor, visceral metastasis, and surgical procedure were risk factors correlated with overall survival. PS, BI, EQ-5D, and NRS improved at 3 months after surgery and these improvements were maintained for 6 months after surgery regardless of the surgical procedure., Conclusions: The significant factors affecting survival after surgical treatment for bone metastases included the primary tumor, presence of visceral metastases, and internal fixation without tumor resection or curettage. Surgical treatment for metastatic bone tumors effectively reduced pain and improved PS, ADL, and QOL postoperatively after 3 months., 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., (© 2021 The Authors.)

Polyacrylic acid-modified titanium peroxide nanoparticles (PAA-TiO x NPs) are promising radiosensitizers that enhance the therapeutic effect of X-ray irradiation after local injection into tumors. However, the mechanism for this reaction has remained unclear with the exception of the involvement of hydrogen peroxide (H 2 O 2 ), which is released by PAA-TiO x NPs to a liquid phase during dispersion. In the present study, a clonogenic assay was used to compare PAA-TiO x NPs with free H 2 O 2 molecules to investigate the effect exerted on the radiosensitivity of cancer cells in vitro. A cell-free dialysis method revealed that a portion of the H 2 O 2 adsorbed onto the PAA-TiO x NPs during synthesis could be released during a treatment regimen. The H 2 O 2 release lasted for 7 h, which was sufficient for one radiation treatment procedure. For in vitro experiments, cultured human pancreatic cancer cells took up PAA-TiO x NPs in 10 min after administration. Interestingly, when the cells were washed with a buffer after treatment with either a PAA-TiO x NP or H 2 O 2 solution, the intracellular H 2 O 2 levels remained higher with PAA-TiO x NP treatment compared with the H 2 O 2 solution treatment. Furthermore, the effects of subsequent X-ray irradiation corresponded to the intracellular H 2 O 2 levels. These results indicate that PAA-TiO x NPs are efficient carriers of H 2 O 2 into cancer cells and thus enhance the radiosensitivity., (Copyright © 2020 Elsevier B.V. All rights reserved.)

We report a case of 50-year-old Japanese male who developed periungual desquamation in hand and feet, during recovery phase of severe COVID-19. As coronary lesions (CALs) have been reported during the recovery phase of severe COVID-19 in children as well as Kawasaki disease, caution may be necessary in adults as well., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The free radical scavenger edaravone is a proven neuroprotective drug for patients with amyotrophic lateral sclerosis (ALS). Our objective was to evaluate the therapeutic effects of edaravone for oxidative stress and anti-oxidative activity in ALS patients., Methods: Twenty-two ALS patients with a disease duration of 2 years, treated by edaravone, and 25 control participants were evaluated according to their clinical scores, including ALS functional rating scale-revised (ALSFRS-R), and serum and cerebrospinal fluid (CSF) markers of oxidative stress dROM and anti-oxidative activity OXY., Results: Serum and CSF markers of anti-oxidative activity OXY were significantly decreased in ALS patients at pre-treatment compared with controls ( ## p < .01), which was improved in the course of edaravone treatment. Both serum and CSF OXY were significantly correlated with ALS clinical scores including ALSFRS-R (*p < .05, **p < .01, ***p < .001). Furthermore, serum OXY at pre-treatment was significantly correlated with a change in the ALSFRS-R score in the sixth cycle of edaravone treatment (*p < .05)., Conclusions: The present study suggests significant correlations between anti-oxidative activity and ALS clinical severity, and the therapeutic efficacy of edaravone for decreased anti-oxidative activity in ALS., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Microneurovascular free muscle transfer is the gold-standard surgical procedure for the reanimation of established facial paralysis. However, the innervation of the transferred muscle by the contralateral facial nerve is usually insufficient to produce a stable smile. Besides, the corner of the mouth sometimes moves unnaturally as if it were being pulled up because of the single-direction movement. Thus, we propose one-stage facial reanimation using free latissimus dorsi (LD)-serratus anterior (SA) combined muscle flap transfer with dual innervation. The LD-SA combined muscle flap was harvested with the thoracodorsal artery and vein as common vessels to move the corner of the mouth bidirectionally for natural smiling. The LD muscle was located in the same direction as the zygomaticus major muscle and reinnervated by dual innervation. The contralateral facial nerve was coapted with the thoracodorsal nerve, and the ipsilateral masseter motor nerve was inserted into the LD muscle by intramuscular neurotization. The 6th or 7th SA muscle was located in the same direction as the risorius muscle and reinnervated by neurorrhaphy of the long thoracic nerve and the thin branch of the ipsilateral masseter motor nerve. Since 2015, seven patients have been treated with this method without complications. On average, SA muscle movement was detected in voluntary biting at 3.1 months, and spontaneous smiling occurred 7.7 months after surgery. All patients developed a spontaneous natural smile. This method for established facial paralysis has the potential to improve the quality of the reconstructed smile and the unstable results of conventional single-innervation-single-muscle transfer., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Periodic paralysis (PP) is a rare disease caused by abnormal excitability of the sarcolemma, resulting in the episodic weakness in extremities. Two major subtypes have been identified: primary/familial PP showing Mendelian inheritance of a mutation in the ion channel genes expressed in skeletal muscle, and secondary/sporadic PP which does not show Mendelian inheritance. Thyrotoxic periodic paralysis (TPP) contributes to the majority of secondary PP cases in Asians and Latin Americans, suggesting that genetic factors may underlie the pathogenesis. In contrast, sporadic periodic paralysis (SPP) has no familial history and no secondary factors. The genetic features associated with SPP in Japanese patients remain unexplored. Here, we investigate whether nine single nucleotide variants (SNVs), rs623011, rs312691, rs393743, rs312692, rs312736, rs992072, rs312732, rs723498, and rs312707, found in TPP and/or SPP in other Asian populations are also associated with Japanese SPP cases. The study cohort included 43 Japanese periodic paralysis patients with no mutations in causative genes (SCN4A, CACNA1S, and KCNJ2), no myotonia, and with euthyroid function. The results showed disease susceptibility for all nine SNVs in our Japanese SPP cohort. One of them, rs312691, was newly confirmed to show susceptibility to SPP. Our results suggest the genetic background underlies periodic paralysis., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Phenylacetic acid (PAA) is one type of natural auxin and widely exists in plants. Previous biochemical studies demonstrate that PAA in plants is synthesized from phenylalanine (Phe) via phenylpyruvate (PPA), but the PAA biosynthetic genes and its regulation remain unknown. In this article, we show that the AROGENATE DEHYDRATASE (ADT) family, which catalyzes the conversion of arogenate to Phe, can modulate the levels of PAA in Arabidopsis. We found that overexpression of ADT4 or ADT5 remarkably increased the amounts of PAA. Due to an increase in PAA levels, ADT4ox and ADT5ox plants can partially restore the auxin-deficient phenotypes caused by treatments with an inhibitor of the biosynthesis of indole-3-acetic acid (IAA), a main auxin in plants. In contrast, the levels of PAA were significantly reduced in adt multiple knockout mutants. Moreover, the levels of PPA are substantially increased in ADT4 or ADT5 overexpression plants but reduced in adt multiple knockout mutants, suggesting that PPA is a key intermediate of PAA biosynthesis. These results provide an evidence that members of the ADT family of Arabidopsis can modulate PAA level via the PPA-dependent pathway., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Andersen-Tawil syndrome (ATS) is a skeletal muscle channelopathy with autosomal dominant inheritance resulting in periodic paralysis, arrhythmia characterized by QT prolongation, and dysmorphic features. The KCNJ2 gene has been identified as the causative gene of ATS. Herein, we reported 2 cases of a 21-year-old man and his mother, with episodic paralytic attacks and/or arrhythmia, which are characteristic of ATS. Both G144A, a reported ATS mutation, and V296F, a novel mutation, were identified in the KCNJ2 gene on the same allele from the proband and his mother, but not from his father. In the present study, we investigated the functional effect of these variants on the potassium channel Kir2.1 and the significance of the double mutation. G144A, V296F, and G144A-V296F mutant channels expressed in cultured cells revealed a loss-of-function effect of these mutations on Kir2.1. The K + currents of G144A and G144A-V296F channels were more suppressed than that of V296F channel alone, whereas was no difference between G144A and G144A-V296F. To our knowledge, a double mutation in the KCNJ2 gene has not been reported previously. While either of 2 mutations potentially causes ATS, the G144A mutation might cause the dominant effect on the patients' clinical presentation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Aminolevulinic acid-based photodynamic therapy (ALA-PDT) has emerged as a cancer treatment due to its high specificity and low side effects. In this study, we aimed to identify possible new drugs targeting transporters highly expressed in normal cells but not in cancer cells, to increase the specificity of ALA-PDT., Method: We used a total of seven cell lines, consisting of two gastric, three prostate, and two lung cell lines, for this purpose. siRNAs and inhibitors of these transporters were added, and PpIX production was evaluated using HPLC to examine the roles of transporters in ALA uptake., Results: No correlation in the expression of transporters was observed among cell lines of the same origin. Two major findings were obtained: PEPT1 and PAT1 were expressed only in normal lung and prostate cells, respectively, but not in their cancerous counterparts. The inhibition of these transporters saw a significant decrease in PpIX production only in normal cells, but not in cancer cells., Conclusion: These findings show that the usage of drugs targeted specifically to highly expressed transporters in normal cells is essential for reducing PpIX accumulation in normal cells in order to increase the specificity of ALA-PDT in cancer., (Copyright © 2019 Elsevier B.V. All rights reserved.)

We present a unique case of symptomatic early neurosyphilis in a non-HIV-infected patient. A 47-year-old man with a history of diabetes mellitus presented with generalized seizures. He did not manifest any neurological deficits. At first, multiple brain tumors were suspected based on findings from magnetic resonance imaging of the brain. However, serological and cerebrospinal fluid tests for syphilis yielded positive results, and the masses were reduced using amoxicillin. Multiple cerebral syphilitic gummas were therefore diagnosed. High-dose penicillin therapy was initiated and syphilitic gummas disappeared after five months. Treponema pallidum could invade the central nervous system at an early phase, and sometimes may be difficult to distinguish from malignant brain tumor. If intracranial lesions are identified in a syphilis-infected patient, cerebral syphilitic gumma should be considered as a differential diagnosis., (Copyright © 2018. Published by Elsevier Ltd.)

The 1,3-beta-D-Glucan (BDG) assay is widely used for the diagnosis of fungal infections, especially in patients with hematologic malignancies. Some antimicrobials have been reported to cause false-positive results for BDG, but there has been no report on the effect of penicillin G (PCG) on BDG levels. We experienced a patient who developed false-positive BDG elevation during the administration of PCG for osteomyelitis due to Streptococcus pneumoniae infection. The serum BDG level increased up to 81.0 pg/ml during the continuous administration of PCG at 24 million units per day. However, chest and paranasal CT scan showed no evidence of fungal infection. The BDG level decreased to 38.0 pg/ml at 14 hours after the discontinuation of PCG. The amount of BDG in one vial of PCG inferred from these serum BDG levels is very similar to the actual BDG concentration in a vial of PCG. Therefore, during the administration of PCG, elevated BDG levels should be interpreted with caution, as they may be false-positive results., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Plants often display a high competence for regeneration under stress conditions. Signals produced in response to various types of stress serve as critical triggers for de novo organogenesis, but the identity of these signaling molecules underlying cellular reprogramming are largely unknown. We previously identified an AP2/ERF transcription factor, WOUND INDUCED DEDIFFERENTIATION1 (WIND1), as a key regulator involved in wound-induced cellular reprogramming in Arabidopsis. In this study, we found that activation of Arabidopsis WIND1 (AtWIND1) in hypocotyl explants of Brassica napus (B. napus) enhances callus formation and subsequent organ regeneration. Gene expression analyses revealed that AtWIND1 enhances expression of B. napus homologs of ENHANCER OF SHOOT REGENERATION1/DORNRÖSCHEN (ESR1/DRN), which is a direct target of WIND1 in Arabidopsis. Further, time-course hormonal analyses showed that an altered balance of endogenous auxin/cytokinin exists in AtWIND1-activated B. napus explants. Our mass spectrometry analyses, in addition, uncovered dynamic metabolomic reprogramming in AtWIND1-activated explants, including accumulation of several compounds, e.g. proline, gamma aminobutyric acid (GABA), and putrescine, that have historically been utilized as additives to enhance plant cell reprogramming in tissue culture. Our findings thus provide new insights into how WIND1 functions to promote cell reprogramming., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disease defined by the presence of eosinophilic hyaline intranuclear inclusions. The initial and main clinical feature of adult-onset NIID is predominantly dementia. We present herein 2 cases of sporadic adult-onset NIID with longstanding urinary disturbance prior to development of other neurological symptoms. Case 1: A 71-year-old woman was admitted after she lost consciousness while bathing. She presented slowly progressive bladder dysfunction starting at the age of 40. Recently, she complained of recurrent light-headedness on standing. Her neurological findings showed miosis, muscle weakness, rigidity, hyporeflexia, sensory disturbance, cerebellar ataxia, and orthostatic hypotension. Case 2: A 68-year-old man was admitted because of episodes of transient loss of consciousness. Ten years earlier, he had developed urinary dysfunction. His neurological findings revealed cognitive dysfunction, cerebellar ataxia, and hyporeflexia. Both patients had leukoencephalopathy and motor-sensory neuropathy. In both cases, diffusion-weighted imaging showed high-intensity signals in the corticomedurally junction; and skin biopsy samples revealed ubiquitin-positive intranuclear inclusions. Therefore, we made a diagnosis of adult-onset NIID. Although numerous cases of this disorder have been reported in the past, there were only a few cases showing the development of other neurological symptoms after longstanding urinary disturbance. Our cases suggest that it is worthwhile considering the possibility of NIID in cases with a long-term history of neurogenic bladder dysfunction., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Implantable Cardioverter-Defibrillator (ICD) shocks have been associated with mortality. However, no study has examined the relation between total shock energy and mortality. The aim of this study is to assess the association of total shock energy with mortality, and to determine the patients who are at risk of this association., Methods: Data from 316 consecutive patients who underwent initial ICD implantation in our hospital between 2000 and 2011 were retrospectively studied. We collected shock energy for 3 years from the ICD implantation, and determined the relation of shock energy on mortality after adjusting confounding factors., Results: Eighty-seven ICD recipients experienced shock(s) within 3 years from ICD implantation and 43 patients had died during the follow-up. The amount of shock energy was significantly associated with all-cause death [adjusted hazard ratio (HR) 1.26 (per 100 joule increase), p < 0.01] and tended to be associated with cardiac death (adjusted HR 1.30, p = 0.08). The survival rate of patients with high shock energy accumulation (≥182 joule) was lower (p < 0.05), as compared to low shock energy accumulation (<182 joule), likewise to no shock. Besides, the relation between high shock energy accumulation and all-cause death was remarkable in the patients with low left ventricular ejection fraction (LVEF ≤40%) or atrial fibrillation (AF)., Conclusions: Increase of shock energy was related to mortality in ICD recipients. This relation was evident in patients with low LVEF or AF., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: The CyberKnife Xsight Lung Tracking (XLT) and 1-View tracking systems can synchronize beam targeting to a visible lung tumor with respiratory motion during irradiation without requiring internal fiducial markers. The systems use a correlation model that relates external marker positions to tumor positions as well as a prediction model that predicts the target's future position. In this study, the correlation and prediction model uncertainties related to the CyberKnife fiducial-free tumor tracking system were evaluated using clinical log data., Methods and Materials: Data from 211 fractions in 42 patients with lung tumors were analyzed. Log files produced by the CyberKnife Synchrony system were acquired after each treatment; the mean correlation and prediction errors for each patient were calculated. Additionally, we examined the tracking tumor-related parameters and analyzed the relationships between the model errors and tracking tumor-related parameters., Results: The overall means ± standard deviations (SDs) of the correlation errors were 0.70 ± 0.43 mm, 0.36 ± 0.16 mm, 0.44 ± 0.22 mm, and 0.95 ± 0.43 mm for the superoinferior (SI), left-right (LR), anteroposterior (AP), and radial directions, respectively. The overall means ± SDs of the prediction errors were 0.13 ± 0.11 mm, 0.03 ± 0.02 mm, 0.03 ± 0.02 mm, and 0.14 ± 0.11 mm for the SI, LR, AP, and radial directions, respectively. There were no significant differences in these errors between the XLT and 1-View tracking methods. The tumor motion amplitude was moderately associated with the correlation error and strongly related to the prediction error in the SI and radial directions., Conclusions: Clinical log data analysis can be used to determine the necessary margin sizes in treatment plans to compensate for correlation and prediction errors in the CyberKnife fiducial-free lung tumor tracking system. The tumor motion amplitude may facilitate margin determination., (Copyright © 2017 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Hepatitis B virus (HBV) surface antigen (HBsAg) loss is one of the treatment goals of chronic HBV infection. Bone marrow stromal cell antigen 2 (BST2) is one of the interferon (IFN)-stimulated genes (ISGs) and inhibits the release of various enveloped viruses. Here we examined the effects of antiviral treatment on HBsAg levels and its intracellular mechanism in HBsAg-producing hepatocytes. In PLC/PRF/5 and Huh1, IFNα-2a treatment decreased HBsAg levels in their conditioned media. Upregulation of interleukin 8 (IL8), toll-like receptor 2 (TLR2) and interferon gamma-induced protein 10 (IP10) mRNAs was associated with the reduction of HBsAg in both PLC/PRF/5 and Huh1. The HBsAg level was upregulated by knockdown of IL8, TLR2 or IP10. Exogenous addition of IL8 enhanced BST2 promoter activity and BST2 mRNA expression. Additionally, knockdown of IL8 could lead to the downregulation of BST2 mRNA. Transfection of poly(I-C) enhanced IL8 and BST2 mRNA expression and inhibited HBsAg secretion from PLC/PRF/5 cells. In conclusion, IL8 might play an important role in the enhancement of BST2 and be involved in HBsAg eradication., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: The management of low-grade glioma (LGG) still remains controversial because the effectiveness of early and extensive resection is unclear, and the use of radiation therapy or chemotherapy is not well-defined. In particular, the importance of prognostic factors for survival remains a matter of discussion. The purpose of this study was to validate prognostic factors for survival in patients with LGG., Materials and Methods: A consecutive series of 55 patients with WHO grade II LGG treated in our institute between 1983 and 2013 were retrospectively reviewed to determine the prognostic factors for survival. All data were retrospectively analyzed from the aspect of baseline characteristics, pathological findings, genetic change, surgical treatments, adjuvant therapies, and survival time. Cox multivariate analysis was performed to determine the prognostic factors for survival., Results: There were 28 patients with diffuse astrocytoma (DA), 21 patients with oligodendroglioma (OG), and 6 patients with oligoastrocytoma (OA) diagnosed on initial surgery. The median overall survival was 193 months and fifteen patients (27.3%) died. A mutation in isocitrate dehydrogenase-1 (IDH1) was found in 72.9% of LGG, and this mutation was positively correlated with methylation of O6-methylguanine-DNA methyltransferase (MGMT) (p=0.02). A better prognosis was significantly associated with combined IDH1 mutation and MGMT methylation status (both positive vs both negative, HR 0.079 [95% CI 0.008-0.579], p=0.012), as well as histology (OG vs DA and OA, HR 0.158 [95% CI 0.022-0.674], p=0.011) and tumor size (<6 cm vs ≥6 cm, HR 0.120 [95% CI 0.017-0.595], p=0.008)., Conclusions: Tumor histology, size and IDH-mutation status are important predictors for prolonged overall survival in patients with LGG and may provide a reliable tool for standardizing future treatment strategies., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Epigenetics plays a role in the regulation of gene expression. Epigenetic changes control gene expression at the transcriptional level. Our previous study suggested that the La protein, which is mainly localized in the nucleus, was associated with hepatitis A virus (HAV) internal ribosomal entry site (IRES)-mediated translation and HAV replication. The aim of this study was to investigate whether epigenetic compounds have effects on HAV IRES-mediated translation and HAV replication. Sirtinol, a sirtuin inhibitor, inhibited HAV IRES-mediated translation in COS7-HAV-IRES cells. Treatment with 10 μM sirtinol resulted in a significant reduction in the intracellular RNA levels of HAV HA11-1299 genotype IIIA in Huh7 cells. Epigenetic treatment with a sirtuin inhibitor may represent a new treatment option for HAV infection. In conclusion, epigenetic control was involved in HAV IRES-dependent translation and HAV replication. Special attention should also be paid to underlying viral diseases in the clinical use of epigenetic treatments for malignancies., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Due to the lack of efficient hepatitis B virus (HBV) infection systems, progress in understanding the role of innate immunity in HBV infection has remained challenging. Here we used human hepatocytes from a humanized severe combined immunodeficiency albumin promoter/enhancer driven-urokinase-type plasminogen activator mouse model for HBV infection. HBV DNA levels in culture medium from these human hepatocytes were 4.8-5.7 log IU/mL between day 16 and day 66 post-infection by HBV genotype C inoculum. HBV surface antigen (HBsAg) was also detected by chemiluminescent immunoassay from day 7 to day 66 post-infection. Western blot analysis revealed that major histocompatibility complex class I-related chain A (MICA), which plays a role in the innate immune system, was induced in HBV-infected human hepatocytes 27 days after infection compared with the uninfected control. MICA was reduced at day 62 and undetectable at day 90. Of interest, MICA expression by human hepatocytes increased after HBV infection and decreased before HBsAg loss. Human hepatocytes derived from chimeric mice with hepatocyte-humanized liver could support HBV genome replication. Further studies of the association between HBV replication and MICA induction should be conducted., (Copyright © 2015 Elsevier Inc. All rights reserved.)