bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep Learning of Simultaneous Intracranial and Scalp EEG for Prediction, Detection, and Lateralization of Mesial Temporal Lobe Seizures
Authors: Li Zan , Fields Madeline , Panov Fedor , Ghatan Saadi , Yener Bülent , Marcuse Lara
Published: November 2021

In people with drug resistant epilepsy (DRE), seizures are unpredictable, often occurring with little or no warning. The unpredictability causes anxiety and much of the morbidity and mortality of seizures. In this work, 102 seizures of mesial temporal lobe onset were analyzed from 19 patients with DRE who had simultaneous intracranial EEG (iEEG) and scalp EEG as part of their surgical evaluation. The first aim of this paper was to develop machine learning models for seizure prediction and detection (i) using iEEG only, (ii) scalp EEG only and (iii) jointly analyzing both iEEG and scalp EEG. The second goal was to test if machine learning could detect a seizure on scalp EEG when that seizure was not detectable by the human eye (surface negative) but was seen in iEEG. The final question was to determine if the deep learning algorithm could correctly lateralize the seizure onset. The seizure detection and prediction problems were addressed jointly by training Deep Neural Networks (DNN) on 4 classes: non-seizure, pre-seizure, left mesial temporal onset seizure and right mesial temporal onset seizure. To address these aims, the classification accuracy was tested using two deep neural networks (DNN) against 3 different types of similarity graphs which used different time series of EEG data. The convolutional neural network (CNN) with the Waxman similarity graph yielded the highest accuracy across all EEG data (iEEG, scalp EEG and combined). Specifically, 1 second epochs of EEG were correctly assigned to their seizure, pre-seizure, or non-seizure category over 98% of the time. Importantly, the pre-seizure state was classified correctly in the vast majority of epochs (>97%). Detection from scalp EEG data alone of surface negative seizures and the seizures with the delayed scalp onset (the surface negative portion) was over 97%. In addition, the model accurately lateralized all of the seizures from scalp data, including the surface negative seizures. This work suggests that highly accurate seizure prediction and detection is feasible using either intracranial or scalp EEG data. Furthermore, surface negative seizures can be accurately predicted, detected and lateralized with machine learning even when they are not visible to the human eye.
Associations Between Nutritional Deficits and Physical Performance in Community-Dwelling Older Adults
Authors: Lu Wan-Hsuan , Giudici Kelly Virecoulon , Rolland Yves , Guyonnet Sophie , Mangin Jean-François , Vellas Bruno , de Souto Barreto Philipe
Published: November 2021

Background: Whether multiple nutritional deficiencies have a synergic effect on mobility loss remains unknown. This study aims to evaluate associations between multi-nutritional deficits and physical performance evolution among community-dwelling older adults.

Methods: We included 386 participants from the Multidomain Alzheimer Preventive Trial (MAPT) (75.6 ± 4.5 years) not receiving omega-3 polyunsaturated fatty acid (PUFA) supplementation and who had available data on nutritional deficits. Baseline nutritional deficits were defined as plasma 25 hydroxyvitamin D <20 ng/ml, plasma homocysteine >14 μmol/L, or erythrocyte omega-3 PUFA index ≤ 4.87% (lower quartile). The Short Physical Performance Battery (SPPB), gait speed, and chair rise time were used to assess physical performance at baseline and after 6, 12, 24, 36, 48, and 60 months. We explored if nutrition-physical performance associations varied according to the presence of low-grade inflammation (LGI) and brain imaging indicators.

Results: Within-group comparisons showed that physical function (decreased SPPB and gait speed, increased chair rise time) worsened over time, particularly in participants with ≥2 nutritional deficits; however, no between-group differences were observed when individuals without deficit and those with either 1 or ≥2 deficits were compared. Our exploratory analysis on nutritional deficit-LGI interactions showed that, among people with ≥2 deficits, chair rise time was increased over time in participants with LGI (adjusted mean difference: 3.47; 95% CI: 1.03, 5.91; p = 0.017), compared with individuals with no LGI.

Conclusions: Accumulated deficits on vitamin D, homocysteine, and omega-3 PUFA were not associated with physical performance evolution in older adults, but they determined declined chair rise performance in subjects with low-grade inflammation.

Clinical Trial Registration: [https://clinicaltrials.gov/ct2/show/NCT00672685], identifier [NCT00672685].
The Integration of the Pre-Treatment Neutrophil-to-Lymphocyte Ratio in the Eighth Edition of the AJCC Staging System for Nasopharynx Cancer
Authors: Liang Zhong-Guo , Zhang Fan , Li Ye , Li Ling , Qu Song , Su Fang , Yu Bin-Bin , Guan Ying , Han Lu , Li Kai-Guo , Zhu Xiao-Dong
Published: November 2021

Objective

The present study aimed to evaluate the role of integrating the pretreatment neutrophil-to-lymphocyte ratio (NLR) into the eighth edition of the AJCC staging system for nasopharynx cancer in an endemic region.

Methods

Between May 2007 and December 2012, a total of 713 cases with NPC were retrospectively analyzed. The separation ability in terms of overall survival (OS), local failure-free survival (LFFS), distant metastasis-free survival (DMFS), and failure-free survival (FFS) was evaluated. The discriminatory ability was assessed using Harrell’s concordance index (c-index). Recursive partitioning analysis (RPA) was conducted and incorporated with pretreatment NLR.

Results

When integrated with NLR, the separate and discriminatory abilities for N classifications were improved in terms of OS and DMFS, but not for T categories. By using Recursive partitioning analysis, five subgroups were generated. Compared with the overall stage, the integration of NLR could not enhance the separate and discriminatory abilities. However, patients in the RPA 4 group gained significant benefits in terms of OS (HR 0.390 (95%CI 0.212-0.716), P = 0.002) and FFS (HR 0.548 (95%CI 0.314-0.958), P = 0.032) from the additional adjuvant chemotherapy after concurrent chemoradiotherapy.

Conclusion

The integration of NLR into the 8th edition of the AJCC staging system could enhance the separation and discriminatory abilities for N classifications, but not for T categories. In addition, patients in the RPA 4 group could benefit from the addition of adjuvant chemotherapy to concurrent chemoradiotherapy.
Autophagy-Induced HDAC6 Activity During Hypoxia Regulates Mitochondrial Energy Metabolism Through the β-Catenin/COUP-TFII Axis in Hepatocellular Carcinoma Cells
Authors: Yan Xiaoyu , Qu Xianzhi , Liu Buhan , Zhao Yuanxin , Xu Long , Yu Sihang , Wang Jian , Wang Liying , Su Jing
Published: November 2021

Hypoxia is one of the main driving forces that results in poor outcomes and drug resistance in hepatocellular carcinoma (HCC). As the critical cellular oxygen sensor, mitochondria respond to hypoxic stress by sending retrograde signals to the nucleus that initiate adaptive metabolic responses and maintain the survival of HCC cells. Increasing evidence suggested autophagy contributes to sustain mitochondrial metabolic and quality control. Understanding how mitochondria communicate with the nucleus and alter transcription may provide promising targets for HCC treatment. In this study, we found mitochondrial undergoes selective degradation by autophagy under hypoxia. Furthermore, autophagy-activated HDAC6 not only promoted the nuclear translocation of β-catenin but also increased the affinity of β-catenin to the transcription repressor chicken ovalbumin upstream promoter-transcription factor 2 (COUP-TF II), which suppressed mitochondrial oxidative phosphorylation-related genes transcription. Our data showed that autophagy served as a critical mediator of integrating mitochondrial energy metabolism and nuclear transcription. HDAC6 may be a potential target for reducing the survival of HCC cells by interrupting mitochondria-nucleus crosstalk.
Molecular Pathogenesis of BCR-ABL-Negative Atypical Chronic Myeloid Leukemia
Authors: Fontana Diletta , Gambacorti-Passerini Carlo , Piazza Rocco
Published: November 2021

Atypical chronic myeloid leukemia is a rare disease whose pathogenesis has long been debated. It currently belongs to the group of myelodysplastic/myeloproliferative disorders. In this review, an overview on the current knowledge about diagnosis, prognosis, and genetics is presented, with a major focus on the recent molecular findings. We describe here the molecular pathogenesis of the disease, focusing on the mechanisms of action of the main mutations as well as on gene expression profiling. We also present the treatment options focusing on emerging targeted therapies.
The Clinical Significance and Transcription Regulation of a DNA Damage Repair Gene, SMC4, in Low-Grade Glioma via Integrated Bioinformatic Analysis
Authors: Wang Yan , Wu Zhisheng
Published: November 2021

Glioma is the most common type of malignant tumor in the central nervous system with an unfavorable prognosis and limited treatment. In this study, we are devoted to addressing the prognostic value of DNA damage repair-related genes in low-grade glioma (LGG). We plotted the landscape of DNA damage repair (DDR)-related genes and identified SMC4 as an independent prognostic marker with integrated bioinformatics analysis, which is overexpressed in different histologic subtypes of glioma. We observed that SMC4 expression is elevated in recurrent LGG patients or those with advanced histologic staging. SMC4 depletion inhibits proliferation and induces increased replication damage in LGG cells. Lastly, we predicted and validated the transcription modulation of SMC4 by a transcription factor, MYB, at the -976bp~ -837bp of the SMC4 promoter region in LGG cells. Together, our study identified SMC4 as a potential prognostic biomarker for LGG patients, which functions to promote cell proliferation by repairing replication damage and the expression of SMC4 could be transcriptionally regulated by MYB.
Intratumoral Heterogeneity and Immune Response Indicators to Predict Overall Survival in a Retrospective Study of HER2-Borderline (IHC 2+) Breast Cancer Patients
Authors: Radziuviene Gedmante , Rasmusson Allan , Augulis Renaldas , Grineviciute Ruta Barbora , Zilenaite Dovile , Laurinaviciene Aida , Ostapenko Valerijus , Laurinavicius Arvydas
Published: November 2021

Breast cancer (BC) categorized as human epidermal growth factor receptor 2 (HER2) borderline [2+ by immunohistochemistry (IHC 2+)] presents challenges for the testing, frequently obscured by intratumoral heterogeneity (ITH). This leads to difficulties in therapy decisions. We aimed to establish prognostic models of overall survival (OS) of these patients, which take into account spatial aspects of ITH and tumor microenvironment by using hexagonal tiling analytics of digital image analysis (DIA). In particular, we assessed the prognostic value of Immunogradient indicators at the tumor–stroma interface zone (IZ) as a feature of antitumor immune response. Surgical excision samples stained for estrogen receptor (ER), progesterone receptor (PR), Ki67, HER2, and CD8 from 275 patients with HER2 IHC 2+ invasive ductal BC were used in the study. DIA outputs were subsampled by HexT for ITH quantification and tumor microenvironment extraction for Immunogradient indicators. Multiple Cox regression revealed HER2 membrane completeness (HER2 MC) (HR: 0.18, p = 0.0007), its spatial entropy (HR: 0.37, p = 0.0341), and ER contrast (HR: 0.21, p = 0.0449) as independent predictors of better OS, with worse OS predicted by pT status (HR: 6.04, p = 0.0014) in the HER2 non-amplified patients. In the HER2-amplified patients, HER2 MC contrast (HR: 0.35, p = 0.0367) and CEP17 copy number (HR: 0.19, p = 0.0035) were independent predictors of better OS along with worse OS predicted by pN status (HR: 4.75, p = 0.0018). In the non-amplified tumors, three Immunogradient indicators provided the independent prognostic value: CD8 density in the tumor aspect of the IZ and CD8 center of mass were associated with better OS (HR: 0.23, p = 0.0079 and 0.14, p = 0.0014, respectively), and CD8 density variance along the tumor edge predicted worse OS (HR: 9.45, p = 0.0002). Combining these three computational indicators of the CD8 cell spatial distribution within the tumor microenvironment augmented prognostic stratification of the patients. In the HER2-amplified group, CD8 cell density in the tumor aspect of the IZ was the only independent immune response feature to predict better OS (HR: 0.22, p = 0.0047). In conclusion, we present novel prognostic models, based on computational ITH and Immunogradient indicators of the IHC biomarkers, in HER2 IHC 2+ BC patients.
Tyrosine-Dependent Phenotype Switching Occurs Early in Many Primary Melanoma Cultures Limiting Their Translational Value
Authors: Najem Ahmad , Wouters Jasper , Krayem Mohammad , Rambow Florian , Sabbah Malak , Sales François , Awada Ahmad , Aerts Stein , Journe Fabrice , Marine Jean-Christophe , Ghanem Ghanem E.
Published: November 2021

The use of patient-derived primary cell cultures in cancer preclinical assays, including drug screens and genotoxic studies, has increased in recent years. However, their translational value is constrained by several limitations, including variability that can be caused by the culture conditions. Here, we show that the medium composition commonly used to propagate primary melanoma cultures has limited their representability of their tumor of origin and their cellular plasticity, and modified their sensitivity to therapy. Indeed, we established and compared cultures from different melanoma patients propagated in parallel in low-tyrosine (Ham’s F10) or in high-tyrosine (Ham’s F10 supplemented with tyrosine or RPMI1640 or DMEM) media. Tyrosine is the precursor of melanin biosynthesis, a process particularly active in differentiated melanocytes and melanoma cells. Unexpectedly, we found that the high tyrosine concentrations promoted an early phenotypic drift towards either a mesenchymal-like or senescence-like phenotype, and prevented the establishment of cultures of melanoma cells harboring differentiated features, which we show are frequently present in human clinical biopsies. Moreover, the invasive phenotype emerging in these culture conditions appeared irreversible and, as expected, associated with intrinsic resistance to MAPKi. In sharp contrast, differentiated melanoma cell cultures retained their phenotypes upon propagation in low-tyrosine medium, and importantly their phenotypic plasticity, a key hallmark of melanoma cells. Altogether, our findings underline the importance of culturing melanoma cells in low-tyrosine-containing medium in order to preserve their phenotypic identity of origin and cellular plasticity.
Clinical Features and Familial Mutations in an Autosomal-Inherited Alport Syndrome Patient With the Presentation of Nephrotic Syndrome
Authors: Wang Dahai , Shan Chunrong , Jing Xinxin , Zhang Qiuye , Chang Hong , Lin Yi
Published: November 2021

Background: The aim of this study was to report the clinical features and mutations in a patient with autosomal-inherited Alport syndrome (AS).

Methods: We examined the clinical data, mutation analysis results, and family tree of a patient with autosomal-inherited AS, who had nephrotic syndrome as her first manifestation.

Results: The proband was a girl of 11 months who presented with nephritic and nephrotic syndromes including gross hematuria but had a normal renal function. Her treatment course was complicated by steroid resistance and a poor response to cyclosporine A and cyclophosphamide pulse therapy. Renal biopsy was performed 2 years after disease onset; light microscopy showed glomerular segmental mesangio-proliferative lesions, and type IV collagen staining showed the loss of the α3 chain in the glomerular and tubular basement membrane (GBM and TBM) and α5 chain loss in the GBM. Electron microscopy showed uneven GBM thickness, with the dense basement membrane (BM) layer obviously delaminated and torn, showing a typical “lace-like” change. The segmental BM was loosened and widened. Her father did not develop microscopic hematuria until 10 years later, while her grandmother had asymptomatic hematuria and proteinuria when the proband was diagnosed. We detected a new COL4A4 mutation in the proband, namely c.1715delG (p.G572Vfs * 81) in exon 24. Her father and grandmother carried the same mutation, but her mother and sister did not.

Conclusions: We found a new potentially pathogenic mutation of COL4A4 in a patient with autosomal-inherited AS, which presented as nephrotic syndrome in infancy.
Xin Su Ning—A Review of Basic and Clinical Pharmacology Integrated With Traditional Chinese Medicine Antiarrhythmic Theory
Authors: Wang Xuan , Wang Taiyi , Ding Shuwen , Ma Yu-Ling
Published: November 2021

Xin Su Ning (XSN) is a patented multicomponent medicine, which was certified in 2005 by the China State Food and Drug Administration to be produced pharmaceutically and to be used clinically. The XSN capsule was developed from an effective formula composed by Prof. Shuwen Ding of Shandong University of Traditional Chinese Medicine. Through more than 30 years of clinical observation, Prof. Ding concluded that XSN has a significant effect on arrhythmia with phlegm-heat heart-disturbed syndrome according to the traditional Chinese medicine (TCM) diagnosis. XSN, derived from a classical TCM formula Huanglian Wen Dan Decoction, is formulated with 11 Chinese herbal medicines to treat cardiac ventricular arrhythmia. Clinical evidence suggests that it is particularly efficacious for the arrhythmias induced by cardiac ischemia and viral myocarditis without obvious adverse reactions being reported. Cellular electrophysiological studies in ventricular myocytes revealed that XSN prolongs the duration and suppresses the amplitude of the action potential (AP), which is supported by the blockage of sodium and potassium channels indicating the characteristics of class I and III antiarrhythmic drugs. A recently reported double-blind, placebo-controlled, multicenter clinical trial of XSN enrolled 861 patients (ChiCTR-TRC-14004180) and showed that XSN significantly inhibited premature ventricular contraction (PVC). The cellular electrophysiological discoveries provided the mechanistic evidence for the clinical efficacy on inhibition of PVC by XSN as demonstrated in the clinical trial. These studies, for the first time, provided exclusive evidence that multicomponent TCM antiarrhythmic medicine can be evaluated using conventional research methods that have been used for antiarrhythmic drug discoveries for decades. We aimed to give a comprehensive review on XSN including its origin with the support of TCM theory, its pre-licensing clinical use and development, and its pharmacological and clinical study discoveries. The review will be summarized with the discoveries reported in a novel network pharmacological study that introduced a weight coefficient, which made it possible to evaluate the pharmacological properties of the TCM formula with regard to its formation based on TCM theory. Limitations regarding XSN’s basic and clinical research and possible future studies are listed. We hope that the advances in how XSN was studied may offer useful guidance on how other TCM could be studied with respect to the integrity of the TCM formulas.
Identifying the Effect of Ursolic Acid Against Triple-Negative Breast Cancer: Coupling Network Pharmacology With Experiments Verification
Authors: Zhang Yubao , Ma Xiaoran , Li Huayao , Zhuang Jing , Feng Fubin , Liu Lijuan , Liu Cun , Sun Changgang
Published: November 2021

Triple negative breast cancer (TNBC) is a subtype of breast cancer with complex heterogeneity, high invasiveness, and long-term poor prognosis. With the development of molecular pathology and molecular genetics, the gene map of TNBC with distinctive biological characteristics has been outlined more clearly. Natural plant extracts such as paclitaxel, vinblastine, colchicine etc., have occupied an important position in the treatment of hormone-independent breast cancer. Ursolic acid (UA), a triterpenoid acid compound derived from apple, pear, loquat leaves, etc., has been reported to be effective in a variety of cancer treatments, but there are few reports on the treatment of TNBC. This study performed comprehensive bioinformatics analysis and in vitro experiments to identify the effect of UA on TNBC treatment and its potential molecular mechanism. Our results showed that UA could not only reduce the proliferation, migration, and invasion in MDA-MB-231 and MDA-MB-468 cell lines with a dose-dependent manner but also induce cell cycle arrest and apoptosis. Meanwhile, we collected the gene expression data GSE45827 and GSE65194 from GEO for comparison between TNBC and normal cell type and obtained 724 DEGs. Subsequently, PLK1 and CCNB1 related to TNBC were screened as the key targets via topological analysis and molecular docking, and gene set enrichment analysis identified the key pathway as the p53 signaling pathway. In addition, quantitative real-time PCR and western blot verified the key genes were PLK1 and CCNB1. In vivo and in vitro experiments showed that UA could inhibit the growth of TNBC cells, and down-regulate the protein expression levels of PLK1 and CCNB1 by mediating p53 signaling pathway. These findings provide strong evidence for UA intervention in TNBC via multi-target therapy.
Tissue Type Differences in ABCB1 Expression and Paclitaxel Tissue Pharmacokinetics in Patients With Esophageal Cancer
Authors: van Eerden Ruben A. G. , van Doorn Leni , de Man Femke M. , Heersche Niels , Doukas Michail , van den Bosch Thierry P. P. , Oomen-de Hoop Esther , de Bruijn Peter , Bins Sander , Ibrahim Eman , Nikkessen Suzan , Friberg Lena E. , Koolen Stijn L. W. , Spaander Manon C. W. , Mathijssen Ron H. J.
Published: November 2021

Background: Data from previous work suggests that there is no correlation between systemic (plasma) paclitaxel exposure and efficacy in patients treated for esophageal cancer. In this trial, we investigated ATP-binding cassette efflux transporter expression and intratumoral pharmacokinetics of paclitaxel to identify changes which could be a first sign of chemoresistance.

Methods: Patients with esophageal cancer treated with paclitaxel and carboplatin (± concomitant radiotherapy) were included. During the first and last cycle of weekly paclitaxel, blood samples and biopsies of esophageal mucosa and tumor tissue were taken. Changes in paclitaxel exposure and expression of ABCB1 (P-glycoprotein) over time were studied in both tumor tissue and normal appearing esophageal mucosa.

Results: ABCB1 was significantly higher expressed in tumor tissue compared to esophageal tissue, during both the first and last cycle of paclitaxel (cycle 1: p < 0.01; cycle 5/6: p = 0.01). Interestingly, ABCB1 expression was significantly higher in adenocarcinoma than in squamous cell carcinoma (p < 0.01). During the first cycle, a trend towards a higher intratumoral paclitaxel concentration was observed compared to the esophageal mucosa concentration (RD:43%; 95%CI: −3% to 111% p = 0.07). Intratumoral and plasma paclitaxel concentrations were significantly correlated during the first cycle (AUC0–48 h: r = 0.72; p < 0.01).

Conclusion: Higher ABCB1 expression in tumor tissue, and differences between histological tumor types might partly explain why tumors respond differently to systemic treatment. Resistance by altered intratumoral paclitaxel concentrations could not be demonstrated because the majority of the biopsies taken at the last cycle of paclitaxel did contain a low amount of tumor cells or no tumor.
Chronic Circadian Rhythm Disturbance Accelerates Knee Cartilage Degeneration in Rats Accompanied by the Activation of the Canonical Wnt/β-Catenin Signaling Pathway
Authors: Song Xiaopeng , Ma Tianwen , Hu Hailong , Zhao Mingchao , Bai Hui , Wang Xinyu , Liu Lin , Li Ting , Sheng Xuanbo , Xu Xinyu , Zhang Xinmin , Gao Li
Published: November 2021

With the gradual deepening of understanding of systemic health and quality of life, the factors affecting osteoarthritis (OA) are not limited to mechanical injury, metabolic abnormality, age and obesity, etc., but circadian rhythm, which plays a non-negligible role in human daily life. The purpose of this study was to explore the molecular mechanism of chronic circadian rhythm disturbance (CRD) inducing cartilage OA-like degeneration. Rats with the anterior cruciate ligament excision transection (ACLT) were used to establish the early-stage OA model (6-week). The light/dark (LD) cycle shifted 12 h per week for 22 weeks in order to establish a chronic CRD model. BMAL1 knockdown (KD) and Wnt/β-catenin pathway inhibition were performed in chondrocytes. The contents of proinflammatory factors and OA biomarkers in serum and chondrocyte secretions were detected by ELISA. Pathological and immunohistochemical staining of articular cartilage indicated the deterioration of cartilage. WB and qPCR were used to evaluate the relationship between matrix degradation and the activation of Wnt/β-catenin signaling pathway in chondrocytes. We found that chronic CRD could cause OA-like pathological changes in knee cartilage of rats, accelerating cartilage matrix degradation and synovial inflammation. The expression of MMP-3, MMP-13, ADAMTS-4, and β-catenin increased significantly; BMAL1, Aggrecan, and COL2A1 decreased significantly in either LD-shifted cartilage or BMAL1-KD chondrocytes. The expression of β-catenin and p-GSK-3β elevated, while p-β-catenin and GSK-3β diminished. The inhibitor XAV-939 was able to mitigated the increased inflammation produced by transfected siBMAL1. Our study demonstrates that chronic CRD disrupts the balance of matrix synthesis and catabolic metabolism in cartilage and chondrocytes, and it is related to the activation of the canonical Wnt/β-catenin signaling pathway.
Farrerol Ameliorated Cisplatin-Induced Chronic Kidney Disease Through Mitophagy Induction via Nrf2/PINK1 Pathway
Authors: Ma Ning , wei Zhentong , Hu Jianqiang , Gu Wenjing , Ci Xinxin
Published: November 2021

Previously, Our study has showed that farrerol can activate Nrf2 and ameliorate cisplatin-induced acute kidney injury (AKI). Mitophagy reportedly can prevent diabetic nephropathy, cisplatin-induced AKI and other related nephropathy. In this study, we evaluated the correlation between mitophagy and the protective effect of the Nrf2 activator farrerol on cisplatin-induced CKD by using C57BL/6 wild-type and Nrf2 knockout mice. We confirmed that Nrf2 and PINK1/Parkin-mediated mitophagy was significantly increased on the 3rd day of cisplatin stimulation but was reduced on the 38th day of cisplatin stimulation. Similar to previous results, farrerol activated Nrf2 on the 38th day of cisplatin administration, subsequently stimulating the Nrf2-targeted antioxidant enzymes HO-1 and NQO1. In addition, farrerol triggered PINK1/Parkin-mediated mitophagy by recruiting the receptor proteins LC3 and p62/SQSTM1, thereby eliminating damaged mitochondria. Furthermore, genetic deletion of Nrf2 reduced PINK1/Parkin-mediated mitophagy activation and led to increased renal tubular necrosis and renal fibrosis. We also found that farrerol alleviated inflammation and renal fibrosis by inhibiting p-NF-κB/NLRP3 and TGF-β/Smad signaling. These data indicated that farrerol effectively inhibited cisplatin-induced inflammation and renal fibrosis by activating Nrf2 and PINK1/Parkin-mediated mitophagy, which provides a potential novel therapeutic target for CKD.
Coupling Matrix Extraction of Microwave Filters by Using One-Dimensional Convolutional Autoencoders
Authors: Zhang Yongliang , Wang Yanxing , Yi Yaxin , Wang Junlin , Liu Jie , Chen Zhixi
Published: November 2021

The tuning of microwave filter is important and complex. Extracting coupling matrix from given S-parameters is a core task for filter tuning. In this article, one-dimensional convolutional autoencoders (1D-CAEs) are proposed to extract coupling matrix from S-parameters of narrow-band cavity filter and apply this method to the computer-aided tuning process. The training of 1D-CAE model consists of two steps. First, in the encoding part, one-dimensional convolutional neural network (1D-CNN) with several convolution layers and pooling layers is used to extract the coupling matrix from the S-parameters during the microwave filters’ tuning procedure. Second, in the decoding part, several full connection layers are employed to reconstruct the S-parameters to ensure the accuracy of extraction. The S-parameters obtained by measurement or simulation exist with phase shift, so the influence of phase shift must be removed. The efficiency of the presented method in this article is validated by a sixth-order cross-coupled filter simulation model tuning example.
Decreased Right Prefrontal Synchronization Strength and Asymmetry During Joint Attention in the Left-Behind Children: A Functional Near-Infrared Spectroscopy Study
Authors: Ding Keya , Wang Hongan , Li Chuanjiang , Liu Fulin , Yu Dongchuan
Published: November 2021

Although there are millions of left-behind children in China, the researches on brain structure and functions in left-behind children are not sufficient at the brain imaging level. This study aimed to explore whether there is decreased prefrontal synchronization during joint attention in left-behind children. Sixty children (65.12 ± 6.54 months, 29 males) with 34 left-behind children were recruited. The functional near-infrared spectroscopy (fNIRS) imaging data from the prefrontal cortex during joint attention, as well as behavioral measures (associated with family income, intelligence, language, and social-emotional abilities), were collected. Results verified that brain imaging data and behavioral measures are correlative and support that left-behind children have deficits in social-emotional abilities. More importantly, left-behind children showed decreased synchronization strength and asymmetry in the right middle frontal gyrus during joint attention. The findings suggest that decreased right prefrontal synchronization strength and asymmetry during joint attention might be vulnerability factors in the development of left-behind children.
Differential Expression of Hypothalamic and Gill-crh System With Osmotic Stress in the Euryhaline Black Porgy, Acanthopagrus schlegelii
Authors: Aruna Adimoolam , Wang Tsan-Ping , Cao Jyun-Cing , Lan Dan-Suei , Nagarajan Ganesan , Chang Ching-Fong
Published: November 2021

The local gill production of corticotropin releasing hormone (crh) and crh-receptor (crhr) is hypothesized to play important roles during seawater (SW) and freshwater (FW) acclimation in euryhaline black porgy (Acanthopagrus schlegelii). The mRNA expression of crh, crhr, and Na+/K+-ATPase (a-nka) was examined in SW and FW diencephalon (Dien) and in the gills at different exposure time by Q-PCR analysis. The in situ hybridization results indicate that crh mRNA hybridization signals were more abundant in FW fish in the gigantocellular (PMgc) and parvocellular (PMpc) part of the magnocellular preoptic nucleus versus SW fish. The crh and crhr-expressing cells were located in basal cells of gill filament. Furthermore, in vitro dexamethasone (DEX) treatment could increase the crh-system in the gill. Increased transcripts of the crh-system in the gill via in vitro and in vivo CRH treatments suggest that CRH may regulate the system in a local manner. The a-Nka cells were localized in the filament and secondary lamellae mitochondria rich cells (MRCs) of FW fish at 8 h and 1 day. a-Nka cells were seen in both filament and lamellae in the FW but much less in SW fish indicating that gills play key roles in black porgy osmoregulation. Gill crh and crhr play important roles in the response to salinity stress.
Transcriptome Analysis Revealed the Mechanism by Which Exogenous ABA Increases Anthocyanins in Blueberry Fruit During Veraison
Authors: Han Tianyu , Wu Wenlong , Li Weilin
Published: November 2021

Blueberry (Vaccinium spp.) is a popular healthy fruit worldwide. The health value of blueberry is mainly because the fruit is rich in anthocyanins, which have a strong antioxidant capacity. However, because blueberry is a non-model plant, little is known about the structural and regulatory genes involved in anthocyanin synthesis in blueberries. Previous studies have found that spraying 1,000 mg/L abscisic acid at the late green stage of “Jersey” highbush blueberry fruits can increase the content of anthocyanins. In this experiment, the previous results were verified in “Brightwell” rabbiteye blueberry fruits. Based on the previous results, the anthocyanin accumulation process in blueberry can be divided into six stages from the late green stage to the mature stage, and the transcriptome was used to systematically analyze the blueberry anthocyanin synthesis process. Combined with data from previous studies on important transcription factors regulating anthocyanin synthesis in plants, phylogenetic trees were constructed to explore the key transcription factors during blueberry fruit ripening. The results showed that ABA increased the anthocyanin content of blueberry fruits during veraison. All structural genes and transcription factors (MYB, bHLH, and WD40) involved in the anthocyanin pathway were identified, and their spatiotemporal expression patterns were analyzed. The expression of CHS, CHI, DFR, and LDOX/ANS in ABA-treated fruits was higher in the last two stages of maturity, which was consistent with the change in the anthocyanin contents in fruits. In general, six MYB transcription factors, one bHLH transcription factor and four WD40 transcription factors were found to change significantly under treatment during fruit ripening. Among them, VcMYBA plays a major role in the regulation of anthocyanin synthesis in ABA signaling. This result preliminarily explained the mechanism by which ABA increases the anthocyanin content and improves the efficiency of the industrial use of blueberry anthocyanins.
How Officials’ Competitive Pressure Affects Sustainable Development Capacity From a Spatial Perspective: Empirical Evidence From China
Authors: Xu He , Wang Kun , Li Guoping , Zhang Yufeng
Published: November 2021

The view of political achievements suggests that officials will prefer to implement measures that benefit their own development in order to seek promotions. In the past, GDP weighed heavily in officials’ appraisals, leading them to develop the economy without regard to sustainability. Now that the central government has incorporated environmental indicators into the officials’ appraisal system, will this lead officials to implement sustainable development strategies to the fullest extent? Are there spillover effects and regional heterogeneity in this role? This paper discusses these questions with the help of entropy method and a spatial Durbin model using data of 30 provincial-level regions in China from 2006 to 2016. The conclusions show that, firstly, the officials’ competitive pressure is beneficial to enhance the sustainable development capacity of the province, but this effect is only effective in western China. Secondly, there is no spillover effect of officials’ competitive pressure on sustainable development capacity; thirdly, foreign direct investment, the proportion of state-owned enterprises and environmental regulations have their own unique effects on sustainable development capacity, and there are spillover effects. Based on these findings, this paper proposes corresponding policy recommendations in terms of officials’ appraisal system, talent training, foreign investment introduction, and state-owned enterprise reform.
Environment-Related and Body-Related Components of the Minimal Self
Authors: Liesner Marvin , Kunde Wilfried
Published: November 2021

Perceptual changes that an agent produces by efferent activity can become part of the agent’s minimal self. Yet, in human agents, efferent activities produce perceptual changes in various sensory modalities and in various temporal and spatial proximities. Some of these changes occur at the “biological” body, and they are to some extent conveyed by “private” sensory signals, whereas other changes occur in the environment of that biological body and are conveyed by “public” sensory signals. We discuss commonalties and differences of these signals for generating selfhood. We argue that despite considerable functional overlap of these sensory signals in generating self-experience, there are reasons to tell them apart in theorizing and empirical research about development of the self.
The Influence of Entrepreneurial Cognition on Business Model Innovation: A Hybrid Method Based on Multiple Regressions and Machine Learning
Authors: Zhou Jian , Yang Jian , Sun Hehe , Liu Yang , Liu Xiao
Published: November 2021

How to achieve business model innovation (BMI) has always been a focus topic in the field of entrepreneurship. Based on cognitive theory, this study takes new ventures as the research object to build a theoretical model to explore the impact of entrepreneurial cognition on BMI choice, its intermediary mechanism, and boundary conditions. We test our framework with a sample of 242 questionnaires; the empirical research results show that entrepreneurial configuration cognition, willing cognition, and ability cognition indirectly affect the BMI of new ventures. Strategic sensitivity (SSE) mediated the relationship between entrepreneurial cognition and BMI; knowledge diversity positively moderates the relationship between SSE and BMI. Machine learning algorithm research has found three prediction models for BMI of new ventures. By constructing a theoretical analysis framework of BMI from the perspective of cognition, the results deepen the relevant research on BMI of new ventures, clarify the source of unique characteristics and capabilities of entrepreneurs, provide a new research perspective for analyzing the impact mechanism of entrepreneurial cognition on BMI, enrich the research results in the field of “situation-cognition behavior,” and further clarify the important role of knowledge in the development of new ventures.
Relationship Between the Early Initiation of Substance Use and Attempted Suicide Among in-School Adolescents in Seven Low- or Middle-Income African Countries: An Analysis of the Global School-Based Student Health Survey Data
Authors: Li Lian , Zhao Yuanzhi , Shi Meijun , Wang Yucheng
Published: November 2021

Background: Preventing suicide among adolescents is an urgent global public-health challenge, especially in Africa. Accordingly, the aim of this study was to examine the relationship between the early initiation (< 12 years old) of substance use (cigarette smoking, alcohol use, and drug use) and attempted suicide among in-school adolescents in seven African countries.

Methods: Data on the early initiation of substance use and on attempted suicide among in-school adolescents over the previous 12 months in Benin, Liberia, Mauritius, Mozambique, Namibia, Seychelles, and the United Republic of Tanzania were collected from Global School-based Student Health Surveys and were pooled to determine the overall prevalence of these behaviors in adolescents. Univariate and multivariate logistic regressions were then performed to evaluate country-specific associations between the early initiation of substance use and attempted suicide in these adolescents, followed by meta-analyses to evaluate overall pooled associations.

Results: In the abovementioned seven African low- or middle-income countries (LMICs), overall weighted prevalences of attempted suicide and early initiation of cigarette smoking, alcohol use, and drug use among in-school adolescents were 16.05, 7.76, 17.68, and 3.48%, respectively. Multivariate logistic regression analyses revealed that relative to non-smoking, the early initiation of smoking was significantly associated with attempted suicide in these adolescents [OR (95% CI) = 1.783 (1.219–2.348)]. Additionally, the relationship between early initiation of cigarette smoking and attempted suicide is mostly driven by a higher association in girls [OR (95% CI) = 1.867 (1.031–2.703)] than boys [OR (95% CI) = 1.392 (0.995−1.789)]. Moreover, relative to not using other drugs, the early and later initiation of other drug use were also significantly associated with attempted suicide in these adolescents [ORs (95% CIs) = 2.455 (1.701–3.208) and 1.548 (1.198–1.898)].

Conclusion: Programs that can eliminate or decrease the early initiation of substance use among adolescents should be implemented in African LMICs to prevent subsequent suicide attempts, especially among adolescent girls.
Grit and Meaning in Life of Chinese Nurses: The Chain Mediating Effect of Social Support and Hope
Authors: Yang Lei , Wu Dongmei
Published: November 2021

Grit is defined as perseverance and passion for long-term goals, and it may affect the stability of the nursing workforce and the physical and mental health of nurses continuously. Meaning in life has received considerable attention from scholars, which is an important component in positive psychology. This study aimed to delve into the relationship between grit and the meaning in life of Chinese nurses. Additionally, we also sought to prove the chain mediating effect of social support and hope on this relationship. An online questionnaire survey was used to collect data from 704 Chinese nurses using the self-made demographic questionnaire with Short Grit Scale (Grit-S), the Perceived Social Support Scale (PSSS), Adult Dispositional Hope Scale (ADHS), and Meaning in Life Questionnaire (MLQ). Moreover, Process version 3.3 plug-in SPSS 25 was used to test the mediation effect between variables. The results showed a strong positive relationship between grit and meaning in life and verified the mediating effect of social support and hope on grit and meaning in life. The results also confirmed the chain mediating model between grit, social support, hope, and meaning in life.
Mental Health Problems Among School-Aged Children After School Reopening: A Cross-Sectional Study During the COVID-19 Post-pandemic in East China
Authors: Wang Jingyi , Wang Yingying , Lin Haijiang , Chen Xiaoxiao , Wang Hao , Liang Hongbiao , Guo Xiaoqin , Fu Chaowei
Published: November 2021

Background: Most studies on mental health problems caused by COVID-19 crisis in children were limited to the period of home quarantine. It remained unclear what adverse impact of the psychosocial stressors caused by school reopening, as well as the transitions in daily activities and social interactions had on mental health in children.

Methods: A total of 6400 students in primary schools were enrolled in a cross-sectional study conducted in East China, between June 26 and July 6, 2020, when schools reopened. Children’s mental health status was assessed by the parent version of Strengths and Difficulties Questionnaire (SDQ). Ultimately, data on a total of 6017 children with completed information on mental health, psychosocial stressors, daily activities, and social interactions were eligible for analysis. The associations of mental health with psychosocial stressors, daily activities, and social interactions were determined by ordinal logistic regression models. Stratified analyses were conducted according to grade, gender, school level, area, and caregiver–child relationship to further observe the effects of stressors on mental status.

Results: The prevalence of borderline, moderately abnormal, and prominently abnormal scores were 7.16, 3.34, and 1.96% for total difficulties, and 13.83, 13.45, and 17.85% for prosocial behavior, respectively. Children with psychological stressors had a significantly higher risk of being in a worse category of mental health status, with the maximum adjusted OR of 7.90 (95% CI 3.33–18.75) in those definitely afraid of inadaptation to study and life styles. Time used in home work and computer games was positively related to mental health problems, while physical exercises and frequency of communication with others was negatively related. The effects of psychological stressors on total difficulties were more evident in middle-high grade students (OR = 7.52, 95% CI 4.16–8.61), boys (OR = 6.95, 95% CI 4.83–8.55), those who lived in Taizhou (OR = 7.62, 95% CI 4.72–8.61) and with poor caregiver–child relationship (OR = 7.79, 95% CI 2.26–8.65).

Conclusion: Emotional and behavioral difficulties, especially less prosocial behavior, were prevalent in primary school children after schools reopened. The Chinese government, communities, schools, and families need to provide more effective support for students’ transition back into the school building and address emotional and behavioral problems for children with difficulties.
Subjective Well-Being in Healthcare Professionals in Colombia: On the Constitution of Subjectivity and the Ethics of Care in Times of the COVID-19 Pandemic
Authors: Barragán-Giraldo Diego Fernando , Anzola-Pardo Giovanni , Guerrero-Lucero Maura Andrea
Published: November 2021

The purpose of this work is to reveal how subjective well-being has been generated in a group of professionals in the healthcare field in Colombia, who carried out postgraduate studies at the time of the pandemic caused by the novel SARS-CoV-2 coronavirus in a synchronous and remote learning course facilitated by employing digital technologies. Two methods were assumed, one was qualitative, taking into account some elements of narrative research and discourse analysis, and the other was quantitative, through a rapid reconnaissance survey. The research assumes the constitution of subjectivity from memory and everyday life, as well as the ethics of care concerning caring for oneself and others, as categories that were (re)signified with the narratives—and as notions that make up a theoretical corpus—to understand subjective well-being.
Examining the Relationship Between Hair Cortisol With Stress-Related and Transdiagnostic Subclinical Measures
Authors: Torrecilla Pilar , Barrantes-Vidal Neus
Published: November 2021

Background: Hair cortisol concentrations (HCC) provide a retrospective examination of long-term cortisol production as a measure of the hypothalamic-pituitary-adrenal (HPA) axis functioning, one of the major neural systems implicated in mediating the effects of stress on mental illness. However, evidence about the relationship between HCC with stressors and symptoms is scattered. In the present study, we aimed to examine the association between HCC and a wide range of stress-related and transdiagnostic subclinical measures in a sample of non-clinical young adults with a wide distribution of schizotypy.

Methods: A total sample of 132 non-clinical young adults recruited at college and technical schools oversampled for schizotypy scores were assessed on distal and proximal stressful experiences, appraisals of stress, traits and symptoms of the affective, psychosis and dissociation spectrums, as well as stress-buffering measures, and provided 3 cm-hair samples.

Results: No significant associations were found between HCC and any of the stress-related and subclinical measures. Only suspiciousness and disorganization showed a trend for a positive association with HCC but the magnitude was small.

Conclusions: The present findings support previous studies indicating an overall lack of concordance between a broad range of stress-related and (sub)clinical phenotypic measures with hair cortisol. This study examined for the first time the relationship of HCC with the non-clinical expression of the psychosis spectrum, that is, schizotypy, which complements previous studies on clinical high risk and established psychosis and offers a promising strategy for studying possible HPA dysfunctions characterizing the subclinical psychosis continuum without the confounds associated to clinical psychosis.