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BackgroundClinical trials enroll patients with active fibrotic nonalcoholic steatohepatitis (NASH) (nonalcoholic fatty liver disease [NAFLD] activity score ≥ 4) and significant fibrosis (F ≥ 2); however, screening failure rates are high following biopsy. We developed new scores to identify active fibrotic NASH using FibroScan and magnetic resonance imaging (MRI).MethodsWe undertook prospective primary (n = 176), retrospective validation (n = 169), and University of California San Diego (UCSD; n = 234) studies of liver biopsy-proven NAFLD. Liver stiffness measurement (LSM) using FibroScan or magnetic resonance elastography (MRE), controlled attenuation parameter (CAP), or proton density fat fraction (PDFF), and aspartate aminotransferase (AST) were combined to develop a two-step strategy-FibroScan-based LSM followed by CAP with AST (F-CAST) and MRE-based LSM followed by PDFF with AST (M-PAST)-and compared with FibroScan-AST (FAST) and MRI-AST (MAST) for diagnosing active fibrotic NASH. Each model was categorized using rule-in and rule-out criteria.ResultsAreas under receiver operating characteristic curves (AUROCs) of F-CAST (0.826) and M-PAST (0.832) were significantly higher than those of FAST (0.744, p = 0.004) and MAST (0.710, p

Abstract Uncontrolled terpenoid emissions from forest trees in Japan may have contributed to high O3 concentrations observed in urban and suburban areas. To estimate ozone formation via a series of reactions between NO x and terpenoids using atmospheric chemistry models, it is important to produce terpenoid emission inventories by collecting all reported emission data for the major tree species in Japan and examining their reliability. In this review, we first describe three different plant terpenoid emission types, i.e., isoprene-emitting type, monoterpene-emitting type with storage tissues and organs, and monoterpene-emitting type without storage tissues and organs. Second, we describe various methods for measuring plant terpenoid emissions, including a recently developed simplified method, and explain their reliability. We emphasized that applicable measurement methods depend on the terpenoid emission types. Data obtained using static chamber methods should not be considered because they have the highest uncertainty resulting from normal chamber materials that are not specific to terpenoid measurements and lack humidity control. Finally, we show the absolute values of the collected emission rates and describe their variability. The deciduous oak species, Quercus serrata and Quercus mongolica var. crispula, and bamboo species, Phyllostachys pubescens and Phyllostachys bambusoides, are strong isoprene emitters. Among the monoterpene emitters, four evergreen broadleaf trees, including three Quercus species, had the highest basal emission rate (BER). The monoterpene storage type conifers Larix kaempferi and Pinus densiflora have relatively lower BERs. Emission data are not available for Castanopsis cuspidata, and seasonal changes in emission rates have not been reported for several major tree species in the top 20 rankings. Within species, the reported emission rates of some tree species differed by threefold. These differences may be attributed to the reliability of the measurement and analytical systems, tree age, leaf morphology, environmental conditions, and genetic diversity. We emphasize the need for reliable measurements to achieve a more precise terpenoid emission inventory for major tree species in Japan.

Abstract Upper limb prostheses are commonly propelled by pneumatic artificial muscles organized in an antagonistic arrangement. Nonetheless, the control of upper limb prostheses under changing/unknown situations is difficult and necessary for a variety of real-world applications. Adaptive control, learning-based control, and robust control have been studied to deal with such challenges. However, their adaptability is insufficient for prostheses used in daily life, which are exposed to variable task levels, user motor characteristics, and prosthetic features. This paper introduces a highly adaptive controller for the first time based on Generative Adversarial Nets and proportional–integral–derivative controller (G-PID controller). G-PID controller comprises a generator for generating compensation actions to enhance PID responsiveness when controlling the unknown/changing system. Moreover, it incorporates a discriminator that receives responses from both a user-preselected reference system and the compensated changing/unknown system, and simultaneously determines the source of these responses. Through continuous updates, the compensator modifies the response of unknown/changing system to align with the reference system, thereby facilitating adaptive control. The G-PID controller’s effectiveness is evaluated through 1-degree of freedom (DoF) joint and 2-DoF shoulder prostheses in simulation experiments, and further validated in prototype experiments focusing on online learning for unknown and time-varying payload. The results demonstrate its ability to deal with diverse types of unknowns/changes, marking a significant advancement towards incorporating prostheses seamlessly into daily life.

Abstract The development of haematopoiesis involves the coordinated action of numerous genes, some of which are implicated in haematological malignancies. However, the biological function of many genes remains elusive and unknown functional genes are likely to remain to be uncovered. Here, we report a previously uncharacterised gene in haematopoiesis, identified by screening mutant embryonic stem cells. The gene, ‘attenuated haematopoietic development (Ahed)’, encodes a nuclear protein. Conditional knockout (cKO) of Ahed results in anaemia from embryonic day 14.5 onward, leading to prenatal demise. Transplantation experiments demonstrate the incapacity of Ahed-deficient haematopoietic cells to reconstitute haematopoiesis in vivo. Employing a tamoxifen-inducible cKO model, we further reveal that Ahed deletion impairs the intrinsic capacity of haematopoietic cells in adult mice. Ahed deletion affects various pathways, and published databases present cancer patients with somatic mutations in Ahed. Collectively, our findings underscore the fundamental roles of Ahed in lifelong haematopoiesis, implicating its association with malignancies.

Purpose: The aim of this study was to show a concrete setting landmark in two component types of round and anatomical oval shapes using three-dimensional (3D) simulation analyses in total knee arthroplasty (TKA). Methods: The patellar resection surface was simulated three-dimensionally using preoperative CT data of 54 patients (68 knees) who underwent TKA with varus knee osteoarthritis. The mediolateral position of the original patellar ridge was examined. The round and anatomical oval patellar components were aligned in the following cases: medial edge setting, patellar ridge setting, maximal size setting. The component ridge position from the medial edge and size in each case were examined. Results: The original patellar ridge was located nearly 40% from the medial edge. In aligning the component to reproduce the original patellar ridge, the medial bone width uncovered with the component was nearly 4 mm in both designs. The component size was significantly smaller as the component was placed more medially. In selecting the maximal size, the round component was aligned more laterally than the original patellar ridge. In contrast, the anatomical oval component enabled to be concomitant with a more appropriate position and size. Conclusion: The position where the medial bone width uncovered with the component was nearly 4 mm, not the medial edge, was found as the best place to reproduce the original patellar ridge in both round and anatomical oval components. Specifically, the anatomical oval component might be more favorable with respect to the component position and size.

Abstract Purpose This study assessed rotational mismatch between components after total knee arthroplasty (TKA) in the supine and standing positions and aimed to investigate the effect of rotational mismatch in the standing position on postoperative patient‐reported outcome measures (PROMs). Methods Seventy‐one patients (71 knees) who underwent TKA for medial knee osteoarthritis were used to investigate rotational mismatches between components. Rotational mismatches between components were examined on postoperative standing whole‐leg and supine knee radiographs using a three‐dimensional‐to‐two‐dimensional model image registration technique, and the angles between the reference axes of the components were measured. Component alignment was evaluated using postoperative computed tomography images, and a questionnaire (2011 version of the Knee Society Score: [KSS 2011]) was mailed to investigate postoperative PROMs. Results In the entire cohort, rotational mismatches in the supine and standing positions were similar (p = 0.9315). In 15% of patients, the mismatch was large (>5°) in the supine position but small (5°) in the standing position (underestimated group). The underestimated group had severe preoperative varus deformity, resulting in external rotation of both femoral and tibial components. Rotational mismatch in the standing position (p = 0.0032) was a significant risk factor for unfavourable PROMs. Patients with a mismatch in the standing position had significantly lower scores than those without a mismatch (p = 0.0215), exceeding the minimal clinically important difference values. Conclusions The underestimated group is clinically important because the surgical procedure and intraoperative assessment of component placement are performed in the supine position. In cases of severe preoperative varus deformity, care should be taken not to place the component in malrotation to avoid rotational mismatch in the standing position. Level of Evidence Ⅳ, Case series.

The simulation-to-reality (sim2real) problem is a common issue when deploying simulation-trained models to real-world scenarios, especially given the extremely high imbalance between simulation and real-world data (scarce real-world data). Although the cycle-consistent generative adversarial network (CycleGAN) has demonstrated promise in addressing some sim2real issues, it encounters limitations in situations of data imbalance due to the lower capacity of the discriminator and the indeterminacy of learned sim2real mapping. To overcome such problems, we proposed the imbalanced Sim2Real scheme (ImbalSim2Real). Differing from CycleGAN, the ImbalSim2Real scheme segments the dataset into paired and unpaired data for two-fold training. The unpaired data incorporated discriminator-enhanced samples to further squash the solution space of the discriminator, for enhancing the discriminator’s ability. For paired data, a term targeted regression loss was integrated to ensure specific and quantitative mapping and further minimize the solution space of the generator. The ImbalSim2Real scheme was validated through numerical experiments, demonstrating its superiority over conventional sim2real methods. In addition, as an application of the proposed ImbalSim2Real scheme, we designed a finger joint stiffness self-sensing framework, where the validation loss for estimating real-world finger joint stiffness was reduced by roughly 41% compared to the supervised learning method that was trained with scarce real-world data and by 56% relative to the CycleGAN trained with the imbalanced dataset. Our proposed scheme and framework have potential applicability to bio-signal estimation when facing an imbalanced sim2real problem.

In recent years, a proliferation of soft actuators tailored for hand rehabilitation has been observed. In particular, modular soft actuators have garnered particular interest due to their capacity for individual customization and joint-specific support, a feature often lacking in whole-finger soft actuators. Despite these advancements, a significant limitation persists: the majority of these actuators facilitate only finger flexion, neglecting the equally vital extension movements required for comprehensive hand rehabilitation. Traditional approaches to achieving multi-degree-of-freedom or bidirectional motion have relied on the integration of multiple chambers within soft actuators. However, this strategy has proven impractical for modular soft actuators, primarily due to spatial constraints within the finger joint. To address this challenge, we introduce a foldable pouch actuator (FPA). Designed as a flat, foldable structure composed of a single sheet, the FPA expands solely upon pressurization, generating the requisite force for finger extension. Notably, the FPA seamlessly integrates with existing modular soft actuators without compromising their structural integrity or functional capabilities, thereby enabling bidirectional support for individual joints. Evaluations using a synthetic finger model achieved a joint flexion torque of 0.17 Nm and estimated an overall extension torque of 0.12 Nm. These advancements were accomplished without compromising the traditional flexion functionality, adding individual joint extension support to the existing capabilities. This study constitutes a substantive leap forward in the utilization of soft actuators for clinical hand rehabilitation applications.

Soft actuators developed for hand rehabilitation show promise, but their practical application requires addressing individual differences and establishing suitable design rules. While joint modular soft actuators offer flexibility for diverse hand dimensions, existing performance validations have only examined a limited number of actuator sizes and neglected crucial factors like joint alignment. Customization efforts have lacked standardization, relying on a trial-and-error approach. Therefore, this study systematically evaluates the impact of actuator design parameters (size and mounting position) on joint range of motion (ROM) and torque, proposing novel design rules based on linear optimization. Experimental assessments, conducted on dummy fingers emulating human biomechanics, provide profound insights into the intricate interplay of design parameters and support performance. The findings strongly advocate maintaining a reference position for stable support, irrespective of actuator size, emphasizing the need to align the actuator with the joint center. The proposed design rules incorporate user-specific finger information, offering customized design rules. Proportionate actuator lengths to single-phalangeal length (PsPL), Proportionate actuator lengths to multi-phalangeal length (PmPL), Proportionate actuator lengths to Range of Motion (PROM), and the Traditional Method are systematically compared. Assistive performances (ROM and torque) and trajectory analysis reveal that the PsPL-designed actuator exhibits the most stable and natural assistive performance. This study emphasizes the importance of understanding actuator deformations for personalized adaptation, providing valuable insights for advancements in assistive and rehabilitative technologies.

Introduction: Regression of malignant melanoma (MM) is a commonly observed phenomenon, which refers to disappearance or loss of all or part of MM. It can be identified both clinically and histologically, and high probability of histological regression of MM (10–58%) has been reported. However, the decapitation of skin tumor has rarely been described in the English literature, and decapitation in MM has not been reported. Here, we report the case of polypoid MM with spontaneous decapitation. Case Presentation: An 81-year-old Japanese woman was referred to our hospital due to a polypoid nodule on her cheek. She was diagnosed with MM at stage IIC (T4bN0M0) by histological examinations. Three weeks after the biopsy, the nodule decapitated spontaneously without bleeding, and an ulcer developed on the base of the polypoid nodule. The histological examination of the additionally resected ulcerative lesion under the nodule revealed infiltration of T cells mainly composed of CD8⁺ natural killer T cells. No recurrence or metastasis has been observed for 4 years. Conclusion: This is the first case report of polypoid MM with spontaneous decapitation, which may be attributed to natural killer T cells. Moreover, this case shows favorable prognosis, while it is said that the regression in thick MM does not have prognostic advantage and polypoid topography has been reported to be related to extremely poor prognosis. Further investigations are needed to evaluate the prognostic advantage of decapitation in MM and other skin tumors.

Aims: To evaluate mid-to long-term patient-reported outcome measures (PROMs) of endoprosthetic reconstruction after resection of malignant tumours arising around the knee, and to investigate the risk factors for unfavourable PROMs. Methods: The medical records of 75 patients who underwent surgery between 2000 and 2020 were retrospectively reviewed, and 44 patients who were alive and available for follow-up (at a mean of 9.7 years postoperatively) were included in the study. Leg length discrepancy was measured on whole-leg radiographs, and functional assessment was performed with PROMs (Toronto Extremity Salvage Score (TESS) and Comprehensive Outcome Measure for Musculoskeletal Oncology Lower Extremity (COMMON-LE)) with two different aspects. The thresholds for unfavourable PROMs were determined using anchor questions regarding satisfaction, and the risk factors for unfavourable PROMs were investigated. Results: The thresholds for favourable TESS and COMMON were 64.8 and 70.4 points, respectively. Multivariate analysis showed that age at surgery (p = 0.004) and postoperative leg length discrepancy (p = 0.043) were significant risk factors for unfavourable TESS results, while age at surgery (p < 0.001) was a significant risk factor for unfavourable COMMON-LE results. Following receiver operating characteristic analysis, the threshold for both TESS and COMMON-LE was 29 years of age at surgery. Additionally, a leg length discrepancy of 8.2 mm was the threshold for unfavourable TESS. Conclusion: Patients aged > 29 years at the time of surgery require appropriate preoperative counselling and adequate postoperative physical and socioemotional support. Reconstruction equivalent to the length of the resected bone can reduce the risk of functional disabilities in daily living. Cite this article: Bone Jt Open 2023;4(12):906–913.

Abstract No report has clarified the frequency and interacting factors affecting sleep disturbance among Asian patients at midterm after total knee arthroplasty (TKA). This study aimed to evaluate the frequency of sleep disturbance at midterm after TKA in a Japanese cohort and to identify intervening factors for sleep. We hypothesized that residual knee pain and decreased functional capability negatively interact with sleep quality after TKA. A total of 209 Japanese participants (average age: 77.1 ± 8.3 years; postoperative follow-up period: 4.5 ± 1.9 years) who underwent primary TKA for knee osteoarthritis were included in this study. Sleep quality, satisfaction, pain, functional capability, joint awareness, and mental condition were evaluated using the Pittsburgh Sleep Quality Index (PSQI), Knee Society Score (KSS) 2011, Forgotten Joint Score (FJS)-12, and 12-Item Short-Form Health Survey (SF-12) Mental Component Summary (MCS). Multivariable analysis was performed to determine the influencing factors on PSQI. The scores for the PSQI, satisfaction with pain level while lying in bed, pain during level walking, functional activity category in the KSS 2011, awareness of the artificial joint in bed at night in the FJS-12, and SF-12 MCS were 6.7 ± 3.0, 5.8 ± 1.8, 1.6 ± 2.3, 62 ± 22, 1.5 ± 1.4, and 56 ± 9.3 on average, respectively. Sleep disturbance (PSQI ≥ 5.5) occurred in 54% of the Japanese participants. Multivariable analysis revealed that high functional capability was a significant factor associated with sleep quality improvement (p

Abstract Background Gasping during resuscitation has been reported as a favorable factor for out-of-hospital cardiac arrest. We examined whether gasping during resuscitation is independently associated with favorable neurological outcomes in patients with refractory ventricular fibrillation or pulseless ventricular tachycardia (VF/pVT) undergoing extracorporeal cardiopulmonary resuscitation ECPR. Methods Data from a 2014 study on advanced cardiac life support for ventricular fibrillation with extracorporeal circulation in Japan (SAVE-J), which examined the efficacy of ECPR for refractory VF/pVT, were analyzed. The primary endpoint was survival with a 6-month favorable neurological outcome in patients who underwent ECPR with or without gasping during resuscitation. Multivariate logistic regression analysis was performed to evaluate the association between gasping and outcomes. Results Of the 454 patients included in the SAVE-J study, data from 212 patients were analyzed in this study after excluding those with missing information and those who did not undergo ECPR. Gasping has been observed in 47 patients during resuscitation; 11 (23.4%) had a favorable neurological outcome at 6 months. Multivariate logistic regression analysis showed that gasping during resuscitation was independently associated with a favorable neurological outcome (odds ratio [OR], 10.58 [95% confidence interval (CI) 3.22–34.74]). The adjusted OR for gasping during emergency medical service transport and on arrival at the hospital was 27.44 (95% CI 5.65–133.41). Conclusions Gasping during resuscitation is a favorable factor in patients with refractory VF/pVT. Patients with refractory VF/pVT with continuously preserved gasping during EMS transportation to the hospital are expected to have more favorable outcomes.

Abstract This study aimed to clarify the clinical utility of the sourcil roundness index (SRI), a novel index for quantifying the asphericity of the acetabular concavity, by determining (1) the difference in the SRI between dysplastic and normal hips and (2) the correlation between the SRI and radiographic parameters of hip dysplasia. We reviewed standing anteroposterior pelvic radiographs of 109 dysplastic and 40 normal hips. The SRI was determined as the ratio of the distance from the medial edge of the sourcil to the most concave point of the acetabular sourcil (A) to the distance from the medial to the lateral edge of the sourcil (B). The formula for SRI is (A/B) × 100–50 (%), with an SRI of 0% indicating a perfectly spherical acetabulum, and higher SRI values indicating a more aspherical shape. The median SRI was greater in patients with hip dysplasia than in normal hips (5.9% vs. − 1.4%; p