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Abstract Objective Defects in RARS2 cause cerebellopontine hypoplasia type 6 (pontocerebellar hypoplasia type 6, PCH6, OMIM: #611523), a rare autosomal recessive inherited mitochondrial disease. Here, we report two male patients and their respective family histories. Methods We describe the clinical presentation and magnetic resonance imaging (MRI) findings of these patients. Whole‐exome sequencing was used to identify the genetic mutations. Results One patient showed hypoglycemia, high lactic acid levels (fluctuating from 6.7 to 14.1 mmol/L), and frequent seizures after birth, with progressive atrophy of the cerebrum, cerebellum, and pons. The other patient presented with early infantile developmental and epileptic encephalopathies (EIDEEs) with an initial developmental delay followed by infantile epileptic spasm syndrome (IESS) at 5 months old, with no imaging changes. Whole‐exome sequencing identified compound heterozygous RARS2 variants c.25A>G (p.I9V) with c.1261C>T (p.Q421*) and c.1A>G (p.M1V) with c.122A>G (p.D41G) in these two patients. Of these loci, c.1261C>T and c.122A>G have not been previously reported. Significance Our findings have expanded the RARS2 gene variant spectrum and present EIDEEs and IESS as phenotypes which deepened the association between PCH6 and RARS2. Plain Language Summary Defects in RARS2 cause cerebellopontine hypoplasia type 6, a rare autosomal recessive inherited mitochondrial disease. Two patients with RARS2 variants were reported in this article. One patient showed hypoglycemia, high lactic acid levels, and frequent seizures after birth, with progressive atrophy of the cerebrum, cerebellum, and Page 3 of 21 Epilepsia OpenFor Review Only pons. The other patient presented with an initial developmental delay followed by refractory epilepsy at 5 months old, with no imaging changes. Our findings deepened the association between PCH6 and RARS2.

Abstract INTRODUCTION Mounting evidence suggests that certain comorbidities may influence the clinical evolution of Alzheimer's dementia (AD). METHODS We conducted logistic regression analyses on the medical history and cognitive health diagnoses of participants in the Australian Imaging, Biomarker & Lifestyle study (n = 2443) to investigate cross‐sectional associations between various comorbidities and mild cognitive impairment (MCI)/AD. RESULTS A mixture of associations were observed. Higher comorbidity of anxiety and other neurological disorders was associated with higher odds of AD, while arthritis, cancer, gastric complaints, high cholesterol, joint replacement, visual defect, kidney and liver disease were associated with lower odds of AD. DISCUSSION This study underscores the links between specific comorbidities and MCI/AD. Further research is needed to elucidate the longitudinal comorbidity‐MCI/AD associations and underlying mechanisms of these associations. Highlights Comorbidities that significantly increased AD odds included anxiety and other neurological disorders. Arthritis, cancer, gastric complaints, high cholesterol, joint replacement, visual defect, kidney and liver disease were associated with lower odds of AD. Alcohol consumption had the most significant confounding effect in the study. Visual‐AD association was modified by age, sex, and APOE ε4 allele status. Anxiety‐AD and depression‐AD associations were modified by sex.

Abstract At present, diabetes mellitus (DM) has been one of the most endangering healthy diseases. Current therapies contain controlling high blood sugar, reducing risk factors like obesity, hypertension, and so on; however, DM patients inevitably and eventually progress into different types of diabetes complications, resulting in poor quality of life. Unfortunately, the clear etiology and pathogenesis of diabetes complications have not been elucidated owing to intricate whole‐body systems. The immune system was responsible to regulate homeostasis by triggering or resolving inflammatory response, indicating it may be necessary to diabetes complications. In fact, previous studies have been shown inflammation plays multifunctional roles in the pathogenesis of diabetes complications and is attracting attention to be the meaningful therapeutic strategy. To this end, this review systematically concluded the current studies over the relationships of susceptible diabetes complications (e.g., diabetic cardiomyopathy, diabetic retinopathy, diabetic peripheral neuropathy, and diabetic nephropathy) and inflammation, ranging from immune cell response, cytokines interaction to pathomechanism of organ injury. Besides, we also summarized various therapeutic strategies to improve diabetes complications by target inflammation from special remedies to conventional lifestyle changes. This review will offer a panoramic insight into the mechanisms of diabetes complications from an inflammatory perspective and also discuss contemporary clinical interventions.

Abstract The research on proximity sensing electronic skin has garnered significant attention. This electronic skin technology enables detection without physical contact and holds vast application prospects in areas such as human‐robot collaboration, human‐machine interfaces, and remote monitoring. Especially in the context of the spread of infectious diseases like COVID‐19, there is a pressing need for non‐contact detection to ensure safe and hygienic operations. This article comprehensively reviews the significant advancements in the field of proximity sensing electronic skin technology in recent years. It covers the principles, as well as single‐type proximity sensors with characteristics such as a large area, multifunctionality, strain, and self‐healing capabilities. Additionally, it delves into the research progress of dual‐type proximity sensors. Furthermore, the article places a special emphasis on the widespread applications of flexible proximity sensors in human‐robot collaboration, human‐machine interfaces, and remote monitoring, highlighting their importance and potential value across various domains. Finally, the paper provides insights into future advancements in flexible proximity sensor technology.

The immunoregulatory role of mesenchymal stem cells (MSCs) in inflammation is heterogeneous and can exhibit anti-inflammatory or proinflammatory properties depending on the microenvironment. We herein observed that the activation of Toll-like receptor 3 (TLR3) by polyinosinic : polycytidylic acid (poly(I : C)) stimulation facilitated the transformation of adipose-derived stem cells (ADSCs) into an anti-inflammatory phenotype. The enhanced anti-inflammatory properties were assessed in a taurocholate-induced pancreatitis model. The results demonstrated that poly(I : C) pretreated ADSCs exhibited enhanced anti-inflammatory properties than untreated ADSCs in taurocholate-induced pancreatitis. Mechanistically, poly(I : C)-treated ADSCs showed increased production and secretion of interleukin-10 (IL-10), which demonstrates a potent ability to alleviate inflammatory signaling cascades in acinar cells. Simultaneously, the heightened anti-inflammatory effects of poly(I : C)-treated ADSCs in pancreatitis were associated with the regulation of macrophage classical/alternative transformation, thereby mitigating inflammatory factor-mediated damage to the pancreatic acinar cell. We propose that TLR3 activation by poly(I : C) is an effective strategy to enhance the anti-inflammatory properties of MSCs, which offers a valuable consideration for improving the therapeutic efficacy of MSCs in inflammatory diseases.

Abstract INTRODUCTION The Centiloid (CL) project was developed to harmonize the quantification of amyloid beta (Aβ) positron emission tomography (PET) scans to a unified scale. The CL neocortical mask was defined using 11C Pittsburgh compound B (PiB), overlooking potential differences in regional distribution among Aβ tracers. We created a universal mask using an independent dataset of five Aβ tracers, and investigated its impact on inter‐tracer agreement, tracer variability, and group separation. METHODS Using data from the Alzheimer's Dementia Onset and Progression in International Cohorts (ADOPIC) study (Australian Imaging Biomarkers and Lifestyle + Alzheimer's Disease Neuroimaging Initiative + Open Access Series of Imaging Studies), age‐matched pairs of mild Alzheimer's disease (AD) and healthy controls (HC) were selected: 18F‐florbetapir (N = 147 pairs), 18F‐florbetaben (N = 22), 18F‐flutemetamol (N = 10), 18F‐NAV (N = 42), 11C‐PiB (N = 63). The images were spatially and standardized uptake value ratio normalized. For each tracer, the mean AD–HC difference image was thresholded to maximize the overlap with the standard neocortical mask. The universal mask was defined as the intersection of all five masks. It was evaluated on the Global Alzheimer's Association Interactive Network (GAAIN) head‐to‐head datasets in terms of inter‐tracer agreement and variance in the young controls (YC) and on the ADOPIC dataset comparing separation between HC/AD and HC/mild cognitive impairment (MCI). RESULTS In the GAAIN dataset, the universal mask led to a small reduction in the variance of the YC, and a small increase in the inter‐tracer agreement. In the ADOPIC dataset, it led to a better separation between HC/AD and HC/MCI at baseline. DISCUSSION The universal CL mask led to an increase in inter‐tracer agreement and group separation. Those increases were, however, very small, and do not provide sufficient benefits to support departing from the existing standard CL mask, which is suitable for the quantification of all Aβ tracers. HIGHLIGHTS This study built an amyloid universal mask using a matched cohort for the five most commonly used amyloid positron emission tomography tracers. There was a high overlap between each tracer‐specific mask. Differences in quantification and group separation between the standard and universal mask were small. The existing standard Centiloid mask is suitable for the quantification of all amyloid beta tracers.

Abstract The propagation of electromagnetic waves will produce multi‐path fading of wireless channel, which degrades communication performance substantially. If multi‐path can be separated, better signal transmission and reception strategies can be designed to weaken or eliminate fading and improve signal transmission performance. However, it is challenging for communication nodes with limited number of antennas. A general multi‐path separation and measurement framework based on single dynamic metasurface antenna is established which rapidly changes patterns within a single pilot symbol period so that equivalent multi‐dimensional received signals can be obtained. Based on the framework, a multi‐path channel estimation scheme is proposed. Specifically, the parameter estimation problem is formulated and present the algorithm based on atomic norm minimisation to estimate parameters including angle of arrival and complex gain of each propagation path. Simulation results illustrate that single dynamic metasurface antenna can approach the capability of a conventional multi‐antenna array, and even using single dynamic metasurface antenna with 1‐bit coding can estimate angle of arrivals and complex gains of multi‐path components accurately.

Abstract This paper studies multi‐antenna covert communication exploiting a public communication link over the wireless fading channel. In particular, a relatively practical covert communication scenario is considered for the first time, where a warden with radiometer may improve its detection accuracy by jointly detecting uplink covert pilot and downlink covert communication. To this end, a joint covert communication system, jointly considering uplink covert pilot, imperfect channel state information issue and downlink covert communication, is proposed and further studied. Specifically, the detection performance of warden and the covertness performance of system are comprehensively studied, respectively. Afterwards, an optimization problem for covert capacity is formulated to maximize overall performance. Then, with our analysis and simplification, an optimal power allocation algorithm is designed for covert capacity accordingly. Our examination shows a win‐win situation has been achieved in the proposed system, that is, covert communication would rarely affect the normal communication of public link and occupy its communication resources. Interestingly enough, we analytically find an invariance property of downlink covert communication that covertness performance is not impacted by noise levels or warden's position. Based on this extraordinary finding, we conclude that the downlink covert communication system can perfectly combat with a powerful warden adopting power trend test method, while the joint covert communication system may resist that through a pilot deception scheme.

Background The aim of this study was to investigate the influence of convolution kernel and iterative reconstruction on the diagnostic performance of radiomics and deep learning (DL) in lung adenocarcinomas. Methods A total of 183 patients with 215 lung adenocarcinomas were included in this study. All CT imaging data was reconstructed with three reconstruction algorithms (ASiR at 0%, 30%, 60% strength), each with two convolution kernels (bone and standard). A total of 171 nodules were selected as the training‐validation set, whereas 44 nodules were selected as the testing set. Logistic regression and a DL framework‐DenseNets were selected to tackle the task. Three logical experiments were implemented to fully explore the influence of the studied parameters on the diagnostic performance. The receiver operating characteristic curve (ROC) was used to evaluate the performance of constructed models. Results In Experiments A and B, no statistically significant results were found in the radiomic method, whereas two and six pairs were statistically significant (P

Abstract To develop a deep learning system based on 3D convolutional neural networks (CNNs), and to automatically predict EGFR‐mutant pulmonary adenocarcinoma in CT images. A dataset of 579 nodules with EGFR mutation status labels of mutant (Mut) or wild‐type (WT) was retrospectively analyzed. A deep learning system, namely 3D DenseNets, was developed to process 3D patches of nodules from CT data, and learn strong representations with supervised end‐to‐end training. The 3D DenseNets were trained with a training subset of 348 nodules and tuned with a development subset of 116 nodules. A strong data augmentation technique, mixup, was used for better generalization. We evaluated our model on a holdout subset of 115 nodules. An independent public dataset of 37 nodules from the cancer imaging archive (TCIA) was also used to test the generalization of our method. Conventional radiomics analysis was also performed for comparison. Our method achieved promising performance on predicting EGFR mutation status, with AUCs of 75.8% and 75.0% for our holdout test set and public test set, respectively. Moreover, strong relations were found between deep learning feature and conventional radiomics, while deep learning worked through an enhanced radiomics manner, that is, deep learned radiomics (DLR), in terms of robustness, compactness and expressiveness. The proposed deep learning system predicts EGFR‐mutant of lung adenocarcinomas in CT images noninvasively and automatically, indicating its potential to help clinical decision‐making by identifying eligible patients of pulmonary adenocarcinoma for EGFR‐targeted therapy.

Background Metastatic breast cancer (MBC) remains an incurable disease worldwide. Tumor gene mutations have evolved and led to drug resistance in the treatment course of MBC. However, data on the mutation profiles and druggable genomic alterations of MBC remain limited, particularly among Chinese patients. Our study aimed to depict the mutation profiles and identify druggable mutations in circulating tumor DNA (ctDNA) in Chinese MBC patients. Methods Targeted deep sequencing of a 1021‐gene panel was performed on 17 blood samples and 5 available tissue samples from 17 Chinese MBC patients. Results We identified 60 somatic mutations in 17 blood samples (sensitivity 100%). Somatic mutations were identified in the blood samples of all patients, and 41.18% (7/17) of patients harbored at least one druggable mutation. A high ctDNA level in plasma is associated with shorter progression‐free survival. Conclusion Targeted deep sequencing of cell free DNA is a highly sensitive, noninvasive method to depict tumor mutation profiles, identify druggable mutations in MBC, and predict patient outcome. Our study shed light on the utility of ctDNA as noninvasive “liquid biopsy” in the management of MBC.

The molecular mechanisms that underlie drought stress responses in kenaf, an important crop for the production of natural fibers, are poorly understood. To address this issue, we describe here the first iTRAQ‐based comparative proteomic analysis of kenaf seedlings. Plants were divided into the following three treatment groups: Group A, watered normally (control); Group B, not watered for 6 days (drought treatment); and Group C, not watered for 5 days and then rewatered for 1 day (recovery treatment). A total of 5014 proteins were detected, including 4932 (i.e., 98.36%) that were matched to known proteins in a BLAST search. We detected 218, 107, and 348 proteins that were upregulated in Group B compared with Group A, Group C compared with Group A, and Group B compared with Group C, respectively. Additionally, 306, 145, and 231 downregulated proteins were detected during the same comparisons. Seventy differentially expressed proteins were analyzed and classified into 10 categories: photosynthesis, sulfur metabolism, amino sugar and nucleotide sugar metabolism, oxidative phosphorylation, ribosome, fatty acid elongation, thiamine metabolism, tryptophan metabolism, plant–pathogen interaction, and propanoate. Kenaf adapted to stress mainly by improving the metabolism of ATP, regulating photosynthesis according to light intensity, promoting the synthesis of osmoregulators, strengthening ion transport signal transmission, and promoting metabolism and cell stability. This is the first study to examine changes in protein expression in kenaf plants exposed to drought stress. Our results identified key drought‐responsive genes and proteins and may provide useful genetic information for improving kenaf stress resistance.

At present, the index of gross profit margin is overestimated in China. However, this problem has not attracted enough attention. This paper explores the theoretical limitations of the current revenue that lead to the overestimation of the gross profit margin. Then, we present the concept of revenue to correct the limitations of the current revenue. Moreover, we test the impact on the information content of gross profit margin under revenue caliber. The findings are as follows: (1) The current revenue includes some unrealized items such as in-price tax, so it is not completely consistent with the definition of revenue from the perspective of accounting, which will lead to the overestimation of gross profit margin. Therefore, the current revenue should exclude the in-price tax, bad debt loss, and cash discount in order to obtain the revenue. The gross profit margin based on the revenue can reflect the profitability of the company’s basic business more objectively. (2) The empirical test shows that the gross profit margin based on the revenue has higher information content compared with the gross profit margin based on the current revenue. (3) The current gross profit margin is overestimated by 1.36 percentage points because of the limitations of the current revenue.

Purpose. To evaluate the ocular pharmacokinetic properties of subretinal conbercept injection in vitrectomized rabbit eyes and to compare them with those by intravitreal injection. Methods. The following groups of New Zealand white rabbits received conbercept injections (0.5 mg/0.05 ml): a subretinal group (subretinal injection in vitrectomized eyes), an intravitreal group (intravitreal injection in vitrectomized eyes), and a control group (intravitreal injection in nonvitrectomized eyes). Drug concentrations in the aqueous humor (AH), the vitreous humor (VH), and the retina were measured by the enzyme-linked immunosorbent assay (ELISA), and pharmacokinetic parameters were calculated. Ophthalmic B-ultrasonography, electroretinogram (ERG), and hematoxylin and eosin (H&E) staining were performed to evaluate the safety of subretinal injection. Results. On the 28th day after injection, the drug level in the subretinal group was significantly higher than that in the intravitreal group in the AH (0.90 ± 0.25 μg/ml and 0.11 ± 0.07 μg/ml, P