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Abstract Emotion recognition in user‐generated videos plays an essential role in affective computing. In general, visual information directly affects human emotions, so the visual modality is significant for emotion recognition. Most classic approaches mainly focus on local temporal information of videos, which potentially restricts their capacity to encode the correlation of long‐range context. To address this issue, a novel network is proposed to recognize emotions in videos. To be specific, a spatio‐temporal correlation‐aware block is designed to depict the long‐range correlations between input tokens, where the convolutional layers are used to learn the local correlations and the inter‐image cross‐attention is designed to learn the long‐range and spatio‐temporal correlations between input tokens. To generate diverse and challenging samples, a dual‐augmentation fusion layer is devised, which fuses each frame with its corresponding frame in the temporal domain. To produce rich video clips, a long‐range sampling layer is designed, which generates clips in a wide range of spatial and temporal domains. Extensive experiments are conducted on two challenging video emotion datasets, namely VideoEmotion‐8 and Ekman‐6. The experimental results demonstrate that the proposed method obtains better performance than baseline methods. Moreover, the proposed method achieves state‐of‐the‐art results on the two datasets. The source code of the proposed network is available at: https://github.com/JinChow/LRCANet.

Abstract Understanding the impact of climate change on the geographical distribution of species is a fundamental requirement for biodiversity conservation and resource management. Quercus oxyphylla, an evergreen oak endemic to China, plays a crucial role in maintaining the ecological stability in subtropical regions and high economic value attributed to its dark and high‐density heartwood, but the existing resources are close to endangered. Currently, limited knowledge exists regarding its distribution and potential influences of climate change on suitable areas. This study utilized 63 occurrence records and Biomod2 platform, to predict changes in suitable areas for Q. oxyphylla under future climate change. The results revealed that (1) Q. oxyphylla showed a pattern of three disjunctive geographical centers in the eastern subregion of subtropical evergreen broad‐leaved forest region (IVA): Qinling‐Daba Mountains, Nanling Mountains and Wuyi Mountains center. Currently, the highly suitable areas concentrated in two zones divided by the Yangtze River, that is, the northern subtropical evergreen and deciduous broad‐leaved forest zone (IVAii) and the mid‐subtropical evergreen broad‐leaved forest zone (IVAi). (2) The temperature‐related variables, such as annual temperature range (Bio7), the mean diurnal range (Bio2), and annual mean temperature (Bio1), were identified as the key determinants of the distribution pattern. Because of its considerable climatic variations in temperature and water conditions, Q. oxyphylla's habitat displayed a wider climate niche and strong physiological tolerance to climate change. (3) Under future climate scenarios, the suitable area of the species was expected to overall expand with significant regional differences. The suitable area in IVAi was expected to expand significantly northward while that in IVAii was expected to gradually shrink. To address the impact of climate change, it is necessary to develop conservation plans focused around the three distribution centers, implement localized and regional conservation policies, and conduct educational outreach among local people.

Abstract Olverembatinib (HQP1351) is a BCR‐ABL1 tyrosine kinase inhibitor with promising clinical activity. It is approved in China for the treatment of patients with chronic myeloid leukemia harboring drug‐resistant mutations, such as T315I. In vitro studies suggested that metabolism of olverembatinib is primarily mediated by cytochrome P450 (CYP3A4). The effects of CYP3A4 inhibition and induction on the pharmacokinetics of olverembatinib were evaluated in an open‐label, 2‐part, fixed‐sequence study in healthy volunteers. In Part 1 of this study, 16 participants received a single oral dose of olverembatinib (20 mg) and the oral CYP3A4 inhibitor itraconazole (200 mg). In Part 2, 16 participants received a single oral dose of olverembatinib (40 mg) and the oral CYP3A4 inducer rifampin (600 mg). To measure pharmacokinetic parameters, serial blood samples were collected after administration of olverembatinib alone and combined with itraconazole or rifampin. Coadministration of olverembatinib with itraconazole increased the peak plasma concentration of olverembatinib, its area under the time‐concentration curve (AUC)0‐last, and AUC0‐inf by 75.63%, 147.06%, and 158.66%, respectively. Coadministration with rifampin decreased these same variables by 61.27%, 74.21%, and 75.19%, respectively. These results confirm that olverembatinib is primarily metabolized by CYP3A4 in humans, suggesting that caution should be exercised with concurrent use of olverembatinib and strong CYP3A4 inhibitors or inducers.

Abstract Background Airborne pollen is a crucial risk factor in allergic rhinitis (AR). The severity of AR symptoms can vary based on pollen type and concentration. This study aimed to estimate the association between exposure to different pollen types and AR risk. Methods We obtained data from patients admitted to the Beijing Tongren Hospital for AR, and data on pollen concentration, meteorological factors, and fine particulate matter (PM2.5) from 13 districts in Beijing from 2016 to 2019. We used a time‐stratified case‐crossover study design and calculated odds ratios (ORs) related to the risk of AR associated with a 10 grain/1000 mm2 increase in total pollen concentrations for specific pollen types. A stratified analysis was conducted to assess whether the associations were varied by age and sex. Results The OR of AR associated with a 10 grain/1000 mm2 increase in the 7‐day average pollen concentration was 1.014 (95% CI: 1.014, 1.015), 1.076 (95% CI: 1.070, 1.082), 1.024 (95% CI: 1.023, 1.025), 1.042 (95% CI: 1.039, 1.045), 1.142 (95% CI: 1.137, 1.147), 1.092 (95% CI: 1.088, 1.097), 1.046 (95% CI: 1.035, 1.058), and 1.026 (95% CI: 1.024, 1.028) for total pollen, Ulmus, Cupressaceae, Populus, Fraxinus, Pinus, Betula, and Artemisia, respectively. Both tree pollen (Ulmus, Cupressaceae, Populus, Fraxinus, Betula, and Pinus) and weed pollen (Artemisia, Chenopodium, and Humulus) were correlated with an increased risk of AR. These associations remained consistent across distinct subgroups defined by both age and sex. Conclusion Exposure to pollen from trees and weeds might be associated with an increased risk of AR. This research provides valuable scientific support for both clinical practitioners and patients with AR regarding the hazards of pollen exposure.

Abstract Background We aimed to analyse genome‐wide transcriptome differences between Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) patients and identify biomarkers that correlate well with muscle magnetic resonance imaging (MRI) and histological fibrofatty replacement in both patients, which have not been reported. Methods One hundred and one male patients with dystrophinopathies (55 DMD and 46 BMD) were enrolled. Muscle‐derived genome‐wide RNA‐sequencing was performed in 31 DMD patients, 29 BMD patients, and 11 normal controls. Fibrofatty replacement was scored on muscle MRI and histological levels in all patients. A unique pipeline, single‐sample gene set enrichment analysis combined with Spearman's rank correlations (ssGSEA‐Cor) was developed to identify the most correlated gene signature for fibrofatty replacement. Quantitative real‐time PCR (qRT‐PCR) analysis, western blot analysis, and single‐nucleus RNA‐sequencing (snRNA‐seq) were performed in the remaining patients to validate the most correlated gene signature. Results Comparative transcriptomic analysis revealed that 31 DMD muscles were characterized by a significant increase of inflammation/immune response and extracellular matrix remodelling compared with 29 BMD muscles (P

Abstract Snowmelt floods are highly hazardous meteorological disasters that can potentially threaten human lives and property. Hence, snowmelt susceptibility mapping (SSM) plays an important role in flood prevention systems and aids emergency responders and flood risk managers. In this paper, a method of identifying snowmelt flood hazards is proposed, and a large‐scale snowmelt flood hazard zonation scheme based on historical recordings and multisource remote sensing data is established. To assess the quality of our approach, the proposed model was tested in the cold and arid region of Xinjiang, China. Overall, 140 historical snowmelt flood events and 27 explanatory factors were selected to construct a geospatial dataset for SSM of the contemporary period. GridSearchCV was used to comprehensively search the candidate parameters from the grid of given parameters obtained with the random forest (RF) algorithm. Then, the geospatial dataset was divided into two subsets: 70% for training and 30% for testing. Next, SSM results were obtained with the RF algorithm using optimized parameters. The results indicate that our optimized RF classifier performs well for the task of SSM, with a high AUC value (0.975) for the test dataset. The validation and analysis suggest that the proposed method can efficiently identify snowmelt flood hazards in undersampled arid areas at a regional scale.

Abstract Objective Anti‐mitochondrial antibodies (AMAs) are associated with idiopathic inflammatory myopathies (IIMs). We aimed to summarize the clinicopathological characteristics, assess circulating cell‐free mitochondrial DNA (ccf‐mtDNA), and circulating cell‐free nuclear DNA (ccf‐nDNA) in AMA‐associated IIMs. Methods Medical records of 37 IIMs patients with AMAs were reviewed. Circulating cell‐free mtDNA and ccf‐nDNA levels in sera from IIMs patients with AMAs (n = 21), disease controls (n = 66) and healthy controls (HCs) (n = 23) were measured and compared. Twenty‐eight immune‐mediated necrotizing myopathy (IMNM) patients, 23 dermatomyositis (DM) patients, and 15 anti‐synthetase syndrome (ASS) patients were enrolled as disease controls. Correlations between variables were analyzed. Results Limb weakness was observed in 75.7% and neck weakness in 56.8% of patients. Cardiac involvement occurred in 51.4% of patients. Muscle pathology revealed 81.1% of IMNM, 5.4% polymyositis, and 13.5% nonspecific myositis. Microinfarction was observed in 8.1% of patients. Serum ccf‐mtDNA levels in AMA‐associated IIMs were significantly higher than those in HCs (p

Morel‐Lavallée lesion is a closed soft tissue degloving injury usually associated with high‐velocity trauma. It most commonly occurs in the thigh, hip, and pelvis. Because such lesions are prone to a missed or delayed diagnosis, it may present a potential risk of infection at the fracture site once it progresses. Therefore, timely identification and management of Morel‐Lavallée lesion is crucial. Moreover, there are no relevant guidelines for the treatment of Morel‐Lavallée lesion. Based on the above facts, we reviewed the etiology, epidemiology, pathophysiology, clinical presentation, imaging features, treatment, prognosis, and complications of Morel‐Lavallée lesion with the aim of providing a comprehensive overview of Morel‐Lavallée lesion, increasing awareness of this injury among orthopaedic surgeons, and thus providing a management algorithm that can be applied to this injury.

Lung cancer is a leading cause of mortality worldwide and shows substantial clinical and biomolecular heterogeneity. Currently, specific therapeutic strategies are lacking, so effective drug targets are urgently needed. E6AP/UBE3A is a multifaceted ubiquitin ligase that controls various signaling pathways implicated in neurological diseases and various cancers; however, its role in lung cancer is incompletely understood. Here, MCM6 was identified as an interacting partner of E6AP using the yeast two‐hybrid assay. MCM2 and MCM4 were then shown to interact with E6AP. E6AP knockout enhanced the ubiquitination of MCM2/4/6, suggesting that E6AP was not the E3 ubiquitin ligase for these three MCM proteins. Ablation of E6AP inhibited proliferation and migration, but had no significant effect on apoptosis in A549 and H1975 cells, and proliferation and migration inhibition was also observed in MCM6 knockdown cells. Furthermore, ablation of MCM6 and E6AP synergistically suppressed the proliferation and migration of A549 and H1975 cells. To verify the above findings in vivo, we established tumor models in nude mice and identified that the tumorigenicity of human lung adenocarcinoma (LUAD) cells was synergistically regulated by MCM6 and E6AP. Moreover, the expression levels of MCM6 and E6AP were higher in LUAD tissues than in adjacent tissues. Furthermore, the expression levels of MCM6 and E6AP were positively correlated in human LUAD samples. Thus, our study suggests that the interaction of E6AP and MCM proteins plays an important role in the progression of LUAD, which might offer potential therapeutic targets for cancer treatment.

Abstract Immune responses induced by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection play a critical role in the pathogenesis and outcome of coronavirus disease 2019 (COVID‐19). However, the dynamic profile of immune responses postinfection by SARS‐CoV‐2 variants of concern (VOC) is not fully understood. In this study, peripheral blood mononuclear cells single‐cell sequencing was performed to determine dynamic profiles of immune response to Prototype, Alpha, Beta, and Delta in a rhesus monkey model. Overall, all strains induced dramatic changes in both cellular subpopulations and gene expression levels at 1 day postinfection (dpi), which associated function including adaptive immune response, innate immunity, and IFN response. COVID‐19‐related genes revealed different gene profiles at 1 dpi among the four SARS‐CoV‐2 strains, including genes reported in COVID‐19 patients with increased risk of autoimmune disease and rheumatic diseases. Delta‐infected animal showed inhibition of translation pathway. B cells, T cells, and monocytes showed much commonality rather than specificity among the four strains. Monocytes were the major responders to SARS‐CoV‐2 infection, and the response lasted longer in Alpha than the other strains. Thus, this study reveals the early immune responses induced by SARS‐CoV‐2 Proto or its variants in nonhuman primates, which is important information for controlling rapidly evolving viruses.

Abstract Patients with colorectal cancer (CRC) and diffuse peritoneal metastasis (PM) are not eligible for surgical intervention. Thus, palliative treatment remains the standard of care in clinical practice. Systemic chemotherapy fails to cause drug accumulation at the lesion sites, while intraperitoneal chemotherapy (IPC) is limited by high clearance rates and associated complications. Given the poor prognosis, a customized OxP/R848@PLEL hydrogel delivery system has been devised to improve the clinical benefit of advanced CRC with diffuse PM. This system is distinguished by its simplicity, security, and efficiency. Specifically, the PLEL hydrogel exhibits excellent injectability and thermosensitivity, enabling the formation of drug depots within the abdominal cavity, rendering it an optimal carrier for IPC. Oxaliplatin (OxP), a first‐line drug for advanced CRC, is cytotoxic and enhances the immunogenicity of tumors by inducing immunogenic cell death. Furthermore, OxP and resiquimod (R848) synergistically enhance the maturation of dendritic cells, promote the expansion of cytotoxic T lymphocytes, and induce the formation of central memory T cells. Moreover, R848 domesticates macrophages to an anti‐tumor phenotype. OxP/R848@PLEL effectively eradicates peritoneal metastases, completely inhibits ascites production, and significantly prolongs mice lifespan. As such, it provides a promising approach to managing diffuse PM in patients with CRC without surgical indications.

Abstract Objective The co‐morbidity of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)/autoimmune nodopathies with nephropathy has been gradually known in recent years. This study was intended to explore the clinical, serological and neuropathological features of seven patients with CIDP/autoimmune nodopathies and nephropathy. Methods Among 83 CIDP patients, seven were identified with nephropathy. Their clinical, electrophysiological and laboratory examination data were collected. The nodal/paranodal antibodies were tested. The sural biopsies were performed in all the patients, and renal biopsies were operated in 6 patients. Results Six patients had chronic onsets and one had an acute onset. Four patients exhibited peripheral neuropathy preceding nephropathy while two showed concurrent onset of neuropathy and nephropathy, and one started with nephropathy. All the patients showed demyelination in electrophysiological examination. Nerve biopsies showed mild to moderate mixed neuropathies including demyelinating and axonal changes in all patients. Renal biopsies showed membranous nephropathy in all 6 patients. Immunotherapy was effective in all patients, with two patients showing good response to corticosteroid treatment alone. Four of the patients were positive to anti‐CNTN1 antibody. Compared with anti‐CNTN1 antibody‐negative patients, antibody‐positive patients had a higher proportion of ataxia (3/4 vs. 1/3), autonomic dysfunction (3/4 vs. 1/3), less frequent antecedent infections (1/4 vs. 2/3), higher cerebrospinal fluid proteins (3.2 g/L vs. 1.69 g/L), more frequent conduction block on electrophysiological examination (3/4 vs. 1/3), higher myelinated nerve fiber density, and positive CNTN1 expression in the glomeruli of kidney tissues. Conclusion Anti‐CNTN1 antibody was the most frequent antibody in this group of patients with CIDP/autoimmune nodopathies and nephropathy. Our study suggested that there might be some clinical and pathological differences between the antibody positive and negative patients.

Abstract Background RNA‐binding protein Quaking‐5 (QKI‐5), a major isoform of QKIs, inhibits tumor progression in non‐small cell lung cancer (NSCLC). However, the underlying molecular mechanisms of QKI‐5 in the cell cycle of NSCLC are still largely unknown. Methods MTT, flow cytometry, and colony formation assays were used to investigate cellular phenotypic changes. Mice xenograft model was used to evaluate the antitumor activities of QKI‐5. Co‐immunoprecipitation, RNA immunoprecipitation (RIP), and RIP sequencing were used to investigate protein–protein interaction and protein–mRNA interaction. Results The QKI‐5 expression was downregulated in NSCLC tissues compared with that in paired normal adjacent lung tissues. Overexpression of QKI‐5 inhibited NSCLC cell proliferative and colony forming ability. In addition, QKI‐5 induced cell cycle arrest at G0/G1 phase through upregulating p21Waf1/Cip1 (p21) expression and downregulating cyclin D1, cyclin‐dependent kinase 4 (CDK4), and CDK6 expressions. Further analyses showed that QKI‐5 interacts with p21 protein and CDK4, CDK6 mRNAs, suggesting a critical function of QKI‐5 in cell cycle regulation. In agreement with in vitro study, the mouse xenograft models validated tumor suppressive functions of QKI‐5 in vivo through altering cell cycle G1‐phase‐associated proteins. Moreover, we demonstrated that QKI‐5 is a direct target of miR‐31. The QKI‐5 expression was anticorrelated with the miR‐31 expression in NSCLC patient samples. Conclusion Our results suggest that the miR‐31/QKI‐5/p21‐CDK4–CDK6 axis might have critical functions in the progression of NSCLC, and targeting this axis could serve as a potential therapeutic strategy for NSCLC.

Abstract PLIN4‐myopathy is a recently identified autosomal dominant muscular disorder caused by the coding 99 bp repeat expansion in PLIN4, presenting with distal or proximal weakness. Here, we report one family and one sporadic case of adult‐onset PLIN4‐associated limb‐girdle weakness, whose diagnoses were achieved by a comprehensive genetic analysis workup. We provided additional evidence that the combination of subsarcolemmal/cytoplasmic ubiquitin/p62 positive deposits and rimmed vacuoles could serve as a strong indicator of PLIN4‐myopathy. Moreover, we found novel myopathological features that were ultrastructural subsarcolemmal filamentous materials and membrane‐bound granulofilamentous inclusions formed by the co‐deposition of disrupted lipid droplets and p62 protein aggregates.

Objective The modified Stoppa combined with iliac fossa approach has gained increasing popularity. Although early clinical outcomes have been satisfactory, extensive long‐term clinical outcomes are relatively scarce. The purpose of this study was to evaluate the medium‐ and long‐term outcomes of this approach for complex acetabular fractures. Methods This was a retrospective study involving 57 patients with complex acetabular fractures from January 2009 to January 2016. All fractures were treated with the modified Stoppa combined with iliac fossa approach. Follow‐up was at least 5 years. Primary outcome measures, including quality of reduction and clinical outcomes, were recorded by an independent observer. Secondary outcome measures included time to surgery, surgical time, intraoperative blood loss, and perioperative complications. Results Fifty‐seven patients (range, 18–80 years) included 46 males and 11 females. There were 32 cases on the left side and 25 cases on the right side. The most common associated injury was pulmonary contusion. According to the Judet–Letournel classification, there were 27 both‐column fractures, 16 anterior column with posterior hemitransverse fractures and 14 T‐type fractures. The average time from injury to surgery was 7.3 days. The average intraoperative blood loss and transfusion were 750.9 ml and 564.3 ml, respectively. All fractures healed within 6 months after surgery. The average follow‐up time was 7.7 years, and there was no loss of follow‐up. The quality of reduction was graded as anatomical in 23 cases (40.4%), imperfect in 22 cases (38.6%), and poor in 12 cases (21.0%). According to grading system of Merle d’ Aubigne and Postel, clinical outcomes at 1 year follow‐up were excellent in 17 cases (29.8%), good in 25 cases (43.9%), fair in four cases (7.0%), and poor in 11 cases (19.3%). The excellent and good rate was 73.7% and the difference was not statistically significant compared with the clinical outcomes at the last follow‐up. Intraoperative complications included four cases of obturator nerve injury and two cases of vascular injury. Postoperative complications included one case of wound delayed healing, two cases of deep vein thrombosis, two cases of avascular necrosis of femoral head, three cases of heterotopic ossification and five cases of post‐traumatic arthritis. Only one of these patients underwent reoperation for femoral head necrosis. Conclusions The modified Stoppa combined with iliac fossa approach can achieve satisfactory reduction quality and hip function. It might be a valuable alternative to the ilioinguinal approach for the surgical management of acetabular fractures.

Abstract Objective The objective of this research was to study the clinical features, genetic characteristics, muscle imaging, and muscle pathological changes of a cohort of Chinese patients with mutations in the valosin‐containing protein (VCP) gene. Methods Nine patients from seven Chinese pedigrees were recruited. Variants were detected by next‐generation sequencing and confirmed by Sanger sequencing. Thigh muscle MRIs were performed in five patients. All the patients received muscle biopsies. Results Seven variants in VCP were identified, and two were novel. All the patients presented with adult‐onset muscle weakness. The appearance of “isolated island sign” or “contra‐isolated island sign” was observed in four of the five the patients on muscle MRIs. Muscle biopsies demonstrated the combination of neuropathic and myopathic changes in seven patients and muscle dystrophic changes in two patients. Notably, rimmed vacuoles and cytoplasmic VCP and p62‐positive protein aggregates were observed in all the patients. Conclusion Our finding of novel variants expanded the mutational spectrum of the VCP gene. This cohort of Chinese patients with VCP mutations mainly present with inclusion body myopathy with predominant limb–girdle distribution. The characteristic pattern of fatty infiltration, especially the “isolated island” and “contra‐isolated island” on muscle MRI, along with rimmed vacuoles in muscle biopsy, provides valuable clues for guiding genetic diagnostic workup.

Abstract Immune checkpoint inhibitor (ICI) clinically benefits cancer treatment. However, the ICI responses are only achieved in a subset of patients, and the underlying mechanisms of the limited response remain unclear. 160 patients with non‐small cell lung cancer treated with anti‐programmed cell death protein‐1 (anti‐PD‐1) or anti‐programmed death ligand‐1 (anti‐PD‐L1) are analyzed to understand the early determinants of response to ICI. It is observed that high levels of intracellular adhesion molecule‐1 (ICAM‐1) in tumors and plasma of patients are associated with prolonged survival. Further reverse translational studies using murine syngeneic tumor models reveal that soluble ICAM‐1 (sICAM‐1) is a key molecule that increases the efficacy of anti‐PD‐1 via activation of cytotoxic T cells. Moreover, chemokine (CXC motif) ligand 13 (CXCL13) in tumors and plasma is correlated with the level of ICAM‐1 and ICI efficacy, suggesting that CXCL13 might be involved in the ICAM‐1‐mediated anti‐tumor pathway. Using sICAM‐1 alone and in combination with anti‐PD‐1 enhances anti‐tumor efficacy in anti‐PD‐1‐responsive tumors in murine models. Notably, combinatorial therapy with sICAM‐1 and anti‐PD‐1 converts anti‐PD‐1‐resistant tumors to responsive ones in a preclinical study. These findings provide a new immunotherapeutic strategy for treating cancers using ICAM‐1.

Abstract A hybrid redundancy (HR) scheme is proposed for the medium‐voltage three‐phase cascaded H‐bridge electronic power transformer (CHB‐EPT) based on the combination of the global redundant power modules and local redundant power modules. A “HOT‐FIRST‐LOCAL‐FIRST” transition strategy is designed to achieve a short transition time. Furthermore, to reduce the power loss of the redundant power modules, an intermittent charging (IC) strategy is proposed for the hot‐reserved redundant power modules. The detailed analysis of the topology shows that the proposed scheme can achieve low cost, high reliability, low power loss, and good transition performance. The performances are verified by simulations and experimental results.

Abstract Objective The present study was intended to analyze the characteristics of myelinated nerve fibers density (MFD) of transthyretin amyloid polyneuropathy (ATTR‐PN) and other similar neuropathies. Methods A total of 41 patients with ATTR‐PN, 58 patients of other common peripheral neuropathies, and 17 age‐and gender‐matched controls who visited the First Hospital of Peking University and performed sural nerve biopsy between June 2007 and August 2021 were included for analysis of MFD. Results Except the vasculitic neuropathy group, the total and small MFD of patients in the ATTR‐PN group were significantly lower than those of other disease groups. There was an obvious negative correlation between the total MFD and the disease course in the ATTR‐PN group. The disease course of early‐onset and late‐onset symptoms was similar, but the loss of large myelinated nerve fibers (MF) was more severe for the latter. In addition, all late‐onset and most early‐onset patients had severely reduced MFD after a 2 years' disease course. The MFD in ATTR‐PN patients was negatively correlated with Neuropathy Impairment Score (NIS) and Norfolk Quality of life‐diabetic neuropathy (Norfolk QOL‐DN) score. Conclusion MF is lost differently in ATTR‐PN and in other common peripheral neuropathies. The late‐onset and early‐onset ATTR‐PN patients have different patterns of loss of large and small MF.

Abstract Affective video content analysis is an active topic in the field of affective computing. In general, affective video content can be depicted by feature vectors of multiple modalities, so it is important to effectively fuse information. In this work, a novel framework is designed to fuse information from multiple stages in a unified manner. In particular, a unified fusion layer is devised to combine output tensors from multiple stages of the proposed neural network. With the unified fusion layer, a bidirectional residual recurrent fusion block is devised to model the information of each modality. Moreover, the proposed method achieves state‐of‐the‐art performances on two challenging datasets, i.e. the accuracy value on the VideoEmotion dataset is 55.8%, and the MSE values on the two domains of EIMT16 are 0.464 and 0.176 respectively. The code of UMFN is available at: https://github.com/yunyi9/UMFN.

Abstract An accurate understanding of the changes in height and weight of children with age is critical to the development of models predicting drug concentrations in children (i.e., physiologically‐based pharmacokinetic models). However, curves describing the growth of a typical population of children may not accurately characterize growth of children with various conditions, such as obesity. Therefore, to develop height and weight versus age growth curves for youth who were diagnosed with type 2 diabetes, we extracted data from electronic medical records. Robust nonlinear models were parameterized to the equations describing height and weight versus age as defined by the Centers for Disease Control and Prevention (CDC). CDC z‐scores were calculated using an internal program. The growth curves and z‐scores were compared to CDC norms. Youth with type 2 diabetes were increasingly heavier than CDC norms from early childhood. Except for a period around puberty, youth with type 2 diabetes were, on average, shorter than CDC norms, resulting in shorter average adult height. Deviations in growth were apparent in youth who develop type 2 diabetes; such deviations may be expected for other conditions as well, and disease‐specific growth curves should be considered during development of model‐informed drug development for pediatric conditions.

Abstract Since the dynamics of thin‐walled structures instantaneously varies during the milling process, accurate and efficient prediction of the in‐process workpiece (IPW) dynamics is critical for the prediction of chatter stability of milling of thin‐walled structures. This article presents a surrogate model of the IPW dynamics of thin‐walled structures by combining Gaussian process regression (GPR) with proper orthogonal decomposition (POD) when IPW dynamics at a large number of cutting positions has to be predicted. The GPR method is used to learn the mapping between a set of the known IPW dynamics and the corresponding cutting positions. POD is used to reduce the order of the matrix assembled by the mode shape vectors at different cutting positions, before the GPR model of the IPW mode shape is established. The computation time of the proposed model is mainly composed of the time taken for predicting a known set of IPW dynamics and the time taken for training GPR models. Simulation shows that the proposed model requires less computation time. Moreover, the accuracy of the proposed model is comparable to that of the existing methods. Comparison between the predicted stability lobe diagram and the experimental results shows that IPW dynamics predicted by the proposed model is accurate enough for predicting the stability of milling of thin‐walled structures.

Abstract Parameter identification (PI) is a cost‐effective approach for estimating the parameters of an electrochemical model for lithium‐ion batteries (LIBs). However, it requires identifiability analysis (IA) of model parameters because identifiable parameters vary with reference data and electrochemical models. Therefore, we propose a PI and IA (PIIA) framework for a robust PI that can adapt to discharge data. The IA results show that the best subset with 15 parameters is determined by the Fisher information matrix and the sample‐averaged RDE criterion under various operating conditions. The identification process based on a genetic algorithm determines the optimal parameters. The identified‐parameter model predicts voltage curves with uncertainty bounds, considering the confidence intervals of identified parameters. Further, we demonstrate that the proposed PIIA framework robustly identifies the parameters of the electrochemical model from experimental data.

Abstract On October 2020, the US Food and Drug Administration (FDA) approved remdesivir as the first drug for the treatment of coronavirus disease 2019 (COVID‐19), increasing remdesivir prescriptions worldwide. However, potential cardiovascular (CV) toxicities associated with remdesivir remain unknown. We aimed to characterize the CV adverse drug reactions (ADRs) associated with remdesivir using VigiBase, an individual case safety report database of the World Health Organization (WHO). Disproportionality analyses of CV‐ADRs associated with remdesivir were performed using reported odds ratios and information components. We conducted in vitro experiments using cardiomyocytes derived from human pluripotent stem cell cardiomyocytes (hPSC‐CMs) to confirm cardiotoxicity of remdesivir. To distinguish drug‐induced CV‐ADRs from COVID‐19 effects, we restricted analyses to patients with COVID‐19 and found that, after adjusting for multiple confounders, cardiac arrest (adjusted odds ratio [aOR]: 1.88, 95% confidence interval [CI]: 1.08–3.29), bradycardia (aOR: 2.09, 95% CI: 1.24–3.53), and hypotension (aOR: 1.67, 95% CI: 1.03–2.73) were associated with remdesivir. In vitro data demonstrated that remdesivir reduced the cell viability of hPSC‐CMs in time‐ and dose‐dependent manners. Physicians should be aware of potential CV consequences following remdesivir use and implement adequate CV monitoring to maintain a tolerable safety margin.

Objective To evaluate the radiological and clinical outcomes of the surgical treatment for transverse and posterior wall fractures using single‐column posterior fixation. Methods From January 2009 to January 2018, a total of 24 patients with transverse and posterior wall acetabular fractures in our center were included in this retrospective study, including 17 males and seven females with a mean age of 47 years and a minimum follow‐up of 1 year. All cases were closed fractures. All fractures were fixed with single‐column fixation via the Kocher–Langenbeck approach. Primary outcome measures, including quality of reduction and clinical outcomes, were recorded by an independent observer, who also noted secondary outcome measures, including time to surgery, surgical time, intraoperative blood loss, and postoperative complications. Results Twenty‐four patients (range, 26–74 years) included 17 males and seven females. There were 14 cases on the left side and 10 cases on the right side. The mean time from injury to surgery was 7.1 days. Mean intraoperative blood loss and surgical time were 405.4 mL and 135.8 min, respectively. The mean follow‐up time was 29.5 months (range 12–96 months). All the acetabular fractures united within 5 months after surgery. The quality of reduction was graded as anatomical in 17 cases (70.8%), imperfect in three cases (12.5%), and poor in four cases (16.7%). According to grading system of Merle d’ Aubigne and Postel, clinical outcomes at the final follow‐up were excellent in 10 cases (41.7%), good in six cases (25.0%), fair in five cases (20.5%), and poor in three cases (12.5%). The excellent and good rate was 66.7%. There was a significant relation between the quality of reduction and clinical outcomes (P

Abstract Objective A group of genes have been reported to be associated with myopathies with tubular aggregates (TAs). Many cases with TAs still lack of genetic clarification. This study aims to explore the genetic background of cases with TAs in order to improve our knowledge of the pathogenesis of these rare pathological structures. Methods Thirty‐three patients including two family members with biopsy confirmed TAs were collected. Whole‐exome sequencing was performed on 31 unrelated index patients and a candidate gene search strategy was conducted. The identified variants were confirmed by Sanger sequencing. The wild‐type and the mutant p.Ala11Thr of ALG14 were transfected into human embryonic kidney 293 cells (HEK293), and western blot analysis was performed to quantify protein expression levels. Results Eleven index cases (33%) were found to have pathogenic variant or likely pathogenic variants in STIM1, ORAI1, PGAM2, SCN4A, CASQ1 and ALG14. Among them, the c.764A>T (p.Glu255Val) in STIM1 and the c.1333G>C (p.Val445Leu) in SCN4A were novel. Western blot analysis showed that the expression of ALG14 protein was severely reduced in the mutant ALG14 HEK293 cells (p.Ala11Thr) compared with wild type. The ALG14 variants might be associated with TAs in patients with complex multisystem disorders. Interpretation This study expands the phenotypic and genotypic spectrums of myopathies with TAs. Our findings further confirm previous hypothesis that genes related with calcium signalling pathway and N‐linked glycosylation pathway are the main genetic causes of myopathies with TAs.

Abstract This work enhances the driving sensitivity of micromechanical vibro‐impact resonators by reducing the output switching gap. Differing from previous works for gap narrowing that either require a dedicated pull‐in bias voltage and stopper structures or post‐fabrication refill processes, the use of the snap‐through technique calls for only the initial activation step without the need for constantly applied voltage or additional process steps. Doing so realizes a final gap spacing from a typical 2‐μm limitation to a 0.9‐μm sub‐micron gap. While probes are used to mechanically initiate the bistable transition in this proof‐of‐concept demonstration, this could be done electrically once properly designed actuation electrodes are available. This transducer gap narrowing technique can help facilitate higher sensitivity for vibro‐impact resonator embedded applications such as zero‐quiescent power communication receivers.

ATM serine/threonine kinase (ATM; previously known as ataxia‐telangiectasia mutated) plays a critical role in maintaining genomic stability and regulates multiple downstream pathways, such as DNA repair, cell cycle arrest, and apoptosis. As a serine/threonine kinase, ATM has an array of downstream phosphorylation substrates, including checkpoint effector checkpoint kinase 2 (CHK2). ATM inhibits cell cycle progression by phosphorylating and activating CHK2, which plays an important role in the formation and development of tumors and participates in DNA repair responses after double‐stranded DNA breaks. In this study, we used a recently developed mammalian functional genetic screening system to explore a series of ATM substrates and their role in DNA damage to enhance our understanding of the DNA damage response. Ubiquilin 4 (UBQLN4), which belongs to the ubiquilin family characterized by its ubiquitin‐like (UBL) and ubiquitin‐associated (UBA) domains, was identified as a new substrate for ATM. UBQLN4 is involved in various intracellular processes, such as autophagosome maturation, p21 regulation, and motor axon morphogenesis. However, the biological function of UBQLN4 remains to be elucidated. In this study, we not only identified UBQLN4 as a substrate for ATM, but also found that UBQLN4 interacts with and stabilizes the anti‐apoptotic proteins Bcl‐2‐related protein A1 (BCL2A1) and Bcl‐2‐like protein 10 (BCL2L10) and prevents mesothelioma cell apoptosis in response to DNA damage. These findings expand our understanding of the role of UBQLN4 in mesothelioma and provide new insights into potential mesothelioma treatments targeting substrates for ATM.

Abstract With the wide applications of dual‐rotor flux‐modulation machines for the growing wind power generations, research activities for the control of dual‐rotor flux‐modulation machines are intensified in recent years. Most of the existing control schemes are based on indirect measurements of the d‐axis inductance, the q‐axis inductance and the stator resistance to achieve high torque density and low torque ripple for the dual‐rotor flux‐modulation machines. However, conventional measurements of the d‐axis inductance, the q‐axis inductance and the stator resistance may suffer from (i) low accuracy and (ii) additional sensor costs. To this end, an adaptive differential evolution algorithm is proposed to identify the machine parameters by considering the magnetic saturation and cross‐coupling issue at low rotational speed of dual‐rotor flux‐modulation machines. Finite element analysis is adopted in simulation to preliminarily monitor the actual machine parameter values based on the length and cross section area of the conductor and inductance matrix computation. Both simulation and experimental results reveal that the adopted adaptive differential evolution algorithm can identify the three parameters more steadily and accurately than the conventional genetic algorithm.

Abstract Background The expansion of GGC repeat in the 5' untranslated region of the NOTCH2NLC has been associated with various neurogenerative disorders of the central nervous system and, more recently, oculopharyngodistal myopathy. This study aimed to report patients with distal weakness with both neuropathic and myopathic features on electrophysiology and pathology who present GGC repeat expansions in the NOTCH2NLC. Methods Whole‐exome sequencing (WES) and long‐read sequencing were implemented to identify the candidate genes. In addition, the available clinical data and the pathological changes associated with peripheral nerve and muscle biopsies were reviewed and studied. Results We identified and validated GGC repeat expansions of NOTCH2NLC in three unrelated patients who presented with progressive weakness predominantly affecting distal lower limb muscles, following negative results in an initial WES. We found intranuclear inclusions with multiple proteins deposits in the nuclei of both myofibers and Schwann cells. The clinical features of these patients are compatible with the diagnosis of distal motor neuropathy and rimmed vacuolar myopathy. Interpretation These phenotypes enrich the class of features associated with NOTCH2NLC‐related repeat expansion disorders (NRED), and provide further evidence that the neurological symptoms of NRED include not only brain, spinal cord, and peripheral nerves damage, but also myopathy, and that overlapping symptoms might exist.

Abstract Objective We aimed to summarize the clinical, genetic, and myopathological features of a cohort of Chinese patients with congenital myasthenic syndrome, and follow up on therapeutic outcomes. Methods The clinical spectrum, mutational frequency of genes, and pathological diagnostic clues of various subtypes of patients with congenital myasthenic syndrome were summarized. Therapeutic effects were followed up. Results Thirty‐five patients from 29 families were recruited. Ten genes were identified: GFPT1 (27.6%), AGRN (17.2%), CHRNE (17.2%), COLQ (13.8%), GMPPB (6.9%), CHAT, CHRNA1, DOK7, COG7, and SLC25A1 (3.4% each, respectively). Sole limb‐girdle weakness was found in patients with AGRN (1/8) and GFPT1 (7/8) mutations, whereas distal weakness was all observed in patients with AGRN (6/8) mutations. Tubular aggregates were only found in patients with GFPT1 mutations (5/6). The patients with GMPPB mutations (2/2) had decreased alpha‐dystroglycan. Acetylcholinesterase inhibitor therapy resulted in no response or worsened symptoms in patients with COLQ mutations, a diverse response in patients with AGRN mutations, and a good response in patients with other subtypes. Albuterol therapy was effective or harmless in most subtypes. Therapy effects became attenuated with long‐term use in patients with COLQ or AGRN mutations. Interpretation The genetic distribution of congenital myasthenic syndrome in China is distinct from that of other ethnic origins. The appearance of distal weakness, selective limb‐girdle myasthenic syndrome, tubular aggregates, and decreased alpha‐dystroglycan were indicative of the specific subtypes. Based on the follow‐up findings, we suggest cautious evaluation of the long‐term efficacy of therapeutic agents in congenital myasthenic syndrome.

Abstract Objective This study aims to report the genotypes and phenotypes of hereditary transthyretin amyloidosis (ATTR) in a large Chinese cohort, yet the clinical and genetic profiles of ATTR remain elusive in mainland China. Methods Fifty‐four patients with molecularly confirmed ATTR from 39 unrelated families were identified by sequencing the TTR gene. Sural nerve biopsies were performed in 40 of these cases. The clinical and electrophysiological data were retrospectively collected and analyzed. Results The male/female ratio was 42:12. The average age of patients at the onset of the disease was 47.8 ± 13.0 years. The late‐onset type occurred in 29 cases (53.7%). Twenty‐two probands (56.4%) had a family history with ATTR. The initial symptoms were limb paresthesia in 33 cases (61.1%), autonomic dysfunction in 15 cases (27.8%), and blurred vision in 6 cases (11.1%). A total of 22 different TTR mutations were identified, including Val30Met (25.6%) in 10 families in North China and Ala97Ser in 4 families (10.3%) in South China. Electrophysiological studies revealed general sensorimotor axonal polyneuropathy in 33/44 cases (75.0%), mixed neuropathy with axonal and demyelinating impairment features in 9/44 cases (20.5%) and isolated carpal tunnel syndrome in two cases. Sural nerve biopsies revealed positive Congo red staining in 16/40 cases (40.0%). Conclusion Chinese patients with ATTR exhibited heterogeneous TTR genotypes and clinical phenotypes. Val30Met remains the most common mutation type in mainland China.

Abstract Background To study the influence of preoperative transcatheter arterial chemoembolization (TACE) on the incidence of microvascular invasion (MVI) and long‐term survival outcomes in hepatocellular carcinoma (HCC) patients. Methods Between January 1, 2010 and December 1, 2014, consecutive HCC patients who underwent curative liver resection were enrolled in this study. Univariable and multivariable regression analyses were used to identify independent predictive factors of MVI. Propensity score matching (PSM) was used to compare the incidences of MVI and prognosis between patients who did and did not receive preoperative TACE. Factors associated with Disease‐Free Survival (DFS) and Overall survival (OS) were identified using Cox regression analyses. Results Of 1624 patients, 590 received preoperative TACE. The incidence of MVI was significantly lower in patients with preoperative TACE than those without preoperative TACE (39.15% vs. 45.36%, p = 0.015). After PSM, the incidences of MVI were similar in the two groups (38.85% vs. 41.10%, p = 0.473). Multivariable regression analysis revealed preoperative TACE to have no impact on the incidence of MVI. Before PSM, survival of patients with preoperative TACE was significantly worse than those without preoperative TACE (p = 0.032 for DFS and p = 0.027 for OS). After PSM, the difference became insignificant (p = 0.465 for DFS and p = 0.307 for OS). After adjustment for other prognostic variables in the propensity‐matched cohort, preoperative TACE was still found not to be associated with DFS and OS after HCC resection. Both before and after PSM, the prognosis of patients was not significantly different between the two groups for BCLC stages 0, A, and B. Conclusions Preoperative TACE did not influence the incidence of MVI and prognosis of patients with HCC who underwent ‘curative’ liver resection.

Abstract Objective This study aimed to investigate mitochondrial changes and the mitochondrial antiviral‐signaling protein (MAVS)‐type I interferon (IFN1) signaling pathway in the muscles of anti‐melanoma differentiation gene 5(MDA5) dermatomyositis (DM) patients. Methods Eleven anti‐MDA5 DM and ten antibody‐negative DM patients were included. Muscle biopsies were performed in all patients. Muscle pathology and mitochondrial morphology in particular were compared between two groups. The expression of MDA5, MAVS, interferon (IFN) regulatory factor 7, and IFN‐stimulated gene 15, which are components of the MAVS‐IFN1 signaling pathway, was measured in muscle specimen. The correlation between MAVS expression in muscles and disease phenotypes and muscle pathology were analyzed. Results Anti‐MDA5 DM showed a significantly lower incidence of the characteristic DM pathology (P