bluuebunny/crossref_metadata_2025 huggingface dataset:
A de novo Variant of ASXL1 Is Associated With an Atypical Phenotype of Bohring-Opitz Syndrome: Case Report and Literature Review
Authors: Zhao Weiqing , Hu Xiao , Liu Ye , Wang Xike , Chen Yun , Wang Yangyang , Zhou Hao
Published: September 2021

Bohring-Opitz syndrome (BOS) is a rare genetic disease first reported by Bohring et al. in 1999. With the recent development of exome sequencing (ES), de novo truncating mutations in the additional sex-combs-like 1 (ASXL1) gene have been causally implicated in BOS. Herein, we describe a 7-month-old girl with intrauterine growth restriction, severe pulmonary infection, seizures, and craniofacial abnormalities (microcephaly, micro/retrognathia, hypertelorism, depressed nasal bridge, low-set ears and hypertrichosis) at birth. At a later stage, the patient developed global developmental delay. We performed ES and identified a de novo heterozygous mutation in ASXL1, namely, c.1210C>T/p.R404*. However, this case did not have trigonocephaly, facial hemangioma, prominent eyes, myopia, BOS posture, or brain abnormalities (enlarged subarachnoid spaces, agenesis of the corpus callosum, moderately enlarged cerebral ventricles, or prominent frontal subarachnoid spaces), which are common characteristics in most patients with BOS-harboring ASXL1 mutations. These new data expand the phenotype of BOS driven by ASXL1 and may assist in more accurately delineating the phenotypes caused by variants of this gene.
Impact of a Multifactorial Educational Training on the Management of Preterm Infants in the Central-Eastern European Region
Authors: Steinbauer Philipp , Klebermass-Schrehof Katrin , Cardona Francesco , Bibl Katharina , Werther Tobias , Olischar Monika , Schmölzer Georg , Berger Angelika , Wagner Michael
Published: September 2021

Background: Differences in management and outcomes of extremely preterm infants have been reported across European countries. Implementation of standardized guidelines and interventions within existing neonatal care facilities can improve outcomes of extremely preterm infants. This study evaluated whether a multifactorial educational training (MET) course in Vienna focusing on the management of extremely preterm infants had an impact on the management of extremely preterm infants in Central-Eastern European (CEE) countries.

Methods: Physicians and nurses from different hospitals in CEE countries participated in a two-day MET in Vienna, Austria with theoretical lectures, bedside teaching, and simulation trainings. In order to evaluate the benefit of the workshops, participants had to complete pre- and post-workshop questionnaires, as well as follow-up questionnaires three and twelve months after the MET.

Results: 162 participants from 15 CEE countries completed the two-day MET at our department. Less invasive surfactant administration (LISA) was only used by 39% (63/162) of the participants. After the MET, 80% (122/152) were planning to introduce LISA, and 66% (101/152) were planning to introduce regular simulation training, which was statistically significantly increased three and twelve months after the MET. Thirty-six percent and 57% of the participants self-reported improved outcomes three and twelve months after the MET, respectively.

Conclusion: Our standardized training in Vienna promoted the implementation of different perinatal concepts including postnatal respiratory management using LISA as well as regular simulation trainings at the participants' home departments. Moreover, our MET contributed to dissemination of guidelines, promoted best-practice, and improved self-reported outcomes.
Self-Care Strategies and Job Satisfaction in Pediatricians: What We Can Do to Prevent Burnout—Results of a Nationwide Survey
Authors: Leiss Ulrike , Schiller Andrea , Fries Jonathan , Voitl Peter , Peyrl Andreas
Published: September 2021

Introduction: Working in the clinical field can be a demanding experience. While reports indicate escalating burnout rates among physicians, further investigation about what physicians can do to prevent burnout is necessary. Our objective was to assess self-care levels among pediatricians and the correlation with job satisfaction in order to subsequently identify protective factors.

Methods: In this nationwide, cross-sectional study, a web-based survey was distributed to all Austrian pediatricians via a mailing list of the Austrian Society of Pediatrics. Self-care was measured with a modified Professional Self-Care Scale (PSCS), which consisted of nine items on a four-point Likert scale (from 1, “totally disagree,” to 4, “totally agree”). Additional items addressed job satisfaction, peer support, and access to professional coaching.

Results: The survey was distributed to 1,450 mailing list contacts, a total of 309 Austrian pediatricians completed the survey (21%). “Family” (M = 3.3) and “Friends” (M = 3.1) were the most highly rated self-care strategies. We found significant differences between pediatricians under 35 years and those aged 50 years and above (z = −4.21, p < 0.001). Peer support appeared to impact job satisfaction substantially. We found differences between pediatricians who frequently talk to colleagues about difficult situations, those who sometimes do so, and those who never do (p < 0.001), with a linear trend indicating increased job satisfaction with more frequent peer support (p < 0.001).

Conclusions: Among all self-care strategies, a stable network of family and friends was highest rated, followed by balanced nutrition. Younger, male pediatricians working in hospital showed to be a vulnerable group with regard to overall self-care. Moreover, higher self-care values were found among those pediatricians who reported to receive peer support on a regular basis. We suggest combined organizational and individual interventions to promote pediatricians' well-being. Organizations should provide the possibility to select a well-balanced diet as well as space and time to consume food and cultivate a work environment that enables communication among peers and facilitates professional coaching. On the personal level, we want to encourage pediatricians to talk to trusted colleagues in challenging clinical situations and to consider working with a professional coach.
Huperzia serrata Extract ‘NSP01’ With Neuroprotective Effects-Potential Synergies of Huperzine A and Polyphenols
Authors: Callizot N. , Campanari ML , Rouvière L , Jacquemot G , Henriques A. , Garayev E , Poindron P.
Published: September 2021

Huperzia serrata (Thunb.) Trevis is widely used in traditional asiatic medicine to treat many central disorders including, schizophrenia, cognitive dysfunction, and dementia. The major alkaloid, Huperzine A (HA), of H. serrata is a well-known competitive reversible inhibitor of acetylcholinesterase (AChE) with neuroprotective effects. Inspired by the tradition, we developed a green one-step method using microwave assisted extraction to generate an extract of H. serrata, called NSP01. This green extract conserves original neuropharmacological activity and chemical profile of traditional extract. The neuroprotective activity of NSP01 is based on a precise combination of three major constituents: HA and two phenolic acids, caffeic acid (CA) and ferulic acid (FA). We show that CA and FA potentiate HA-mediated neuroprotective activity. Importantly, the combination of HA with CA and FA does not potentiate the AChE inhibitory property of HA which is responsible for its adverse side effects. Collectively, these experimental findings demonstrated that NSP01, is a very promising plant extract for the prevention of Alzheimer’s disease and memory deficits.
Kakkonto Inhibits Cytokine Production Induced by Rhinovirus Infection in Primary Cultures of Human Nasal Epithelial Cells
Authors: Saito Natsumi , Kikuchi Akiko , Yamaya Mutsuo , Deng Xue , Sugawara Mitsuru , Takayama Shin , Nagatomi Ryoichi , Ishii Tadashi
Published: September 2021

Rhinovirus (RV) is a primary etiologic agent of common cold that can subsequently acutely exacerbate bronchial asthma or chronic obstructive pulmonary disease. Kakkonto (Ge-gen-tang in Chinese), one of the most frequently prescribed traditional Japanese (Kampo) medicines, is used for treating common cold, shoulder stiffness, or inflammatory diseases of the upper body. Previous experimental studies have indicated that kakkonto exerts antiviral and anti-inflammatory effects on the influenza virus and the human respiratory syncytial virus. However, there is a lack of reports investigating the efficacy of kakkonto in RV infection. Hence, the aim of the current study was to investigate the effects of kakkonto on RV infection of human nasal epithelial (HNE) cells. HNE cells obtained via endoscopic sinus surgery were cultured and infected with RV14, with or without kakkonto treatment. The supernatants from the cells were collected, and the RV14 titer and cytokine levels were assessed. Reverse transcription-polymerase chain reaction was performed to determine the amount of viral RNA, while the level of nuclear factor kappa B (NF-κB) subunits in the nucleus was assessed by enzyme-linked immunosorbent assay. Although kakkonto treatment did not reduce RV14 titer or RNA levels, indicating that it did not inhibit RV14 proliferation, it was found to reduce the production of specific pro-inflammatory cytokines, including interleukin (IL)-8, tumor necrosis factor (TNF)-α, and monocyte chemotactic protein-1 (MCP-1). Unlike that observed with the kakkonto extract, none of the crude drugs contained in kakkonto reduced IL-8 level. Furthermore, though kakkonto treatment significantly reduced p50 levels, it did not impact the p65 subunit of NF-κB. These results indicated that kakkonto can inhibit inflammation caused by RV infection and may exert an immunomodulatory effect on HNE cells. This is the first report to elucidate the effects of kakkonto extract on RV infection in primary cultures of HNE cells, providing evidence that kakkonto may act as an effective therapy for RV infection and subsequent airway inflammation.
Efficacy of a Traditional Herbal Formula, Banha-Sasim-Tang in Functional Dyspepsia Classified as Excess Pattern
Authors: Kim Yun Hee , Kim Jun Young , Kwon O-Jin , Jung So Young , Joung Jin-Yong , Yang Chang Sop , Lee Jun-Hwan , Cho Jung-Hyo , Son Chang-Gue
Published: September 2021

This study evaluated the efficacy and safety of Banha-sasim-tang (BST) in patients with functional dyspepsia (FD). BST (Banxia-xiexin-tang in traditional Chinese medicine and Hange-shashin-to in Kampo medicine) is traditionally prescribed for the treatment of dyspepsia with epigastric stiffness and gastric fullness in China, Japan, and Korea. Patients with FD were randomly administered an oral dose (10 g) of BST syrup or placebo, twice a day for 4 weeks. The primary outcome was the symptom checklist part of the Nepean dyspepsia index (NDI). The secondary outcomes were the quality of life (QoL) part of the NDI, functional dyspepsia-related QoL (FD-QoL), and visual analog scale (VAS). A total of 60 patients with FD were screened, and 50 were randomized into BST group (n = 25) and placebo group (n = 25). Two patients in the placebo group withdrew before the start of the treatment. Administration of BST syrup resulted in improvement in the symptom-related NDI score in the BST group compared with that in the control group; however, the difference was not significant. BST syrup significantly improved “fullness after eating” index of NDI at follow-up time point (2.88 ± 2.65 vs 4.78 ± 2.69, p = 0.0081). In the total score of the QoL section of the NDI and FD-QoL scales, there was no significant improvement in the BST group compared to that in the placebo group. With regard to improvement in overall FD symptoms, the VAS scale showed improvement in both groups, but the difference was not significant. Interestingly, follow-up investigation showed a significantly beneficial effect of BST on FD symptoms, when compared to placebo. Significant improvement observed in VAS score (39.60 ± 22.29 vs 52.17 ± 20.55, p = 0.048). This indicated that the effect of BST lasted even after the completion of the medication regimen. Overall, our data suggest that while BST showed no significant improvement in the symptom-related NDI score and the QoL related scores in NDI and FD-QoL after 4 weeks of treatment, it effectively improved the VAS score and fullness after eating-related symptoms in the follow-up visit.

Clinical Trial Registration:https://cris.nih.go.kr; Identifier KCT 0002013
Xanthoceras sorbifolium Bunge: A Review on Botany, Phytochemistry, Pharmacology, and Applications
Authors: Zang Erhuan , Qiu Bin , Chen Namuhan , Li Caifeng , Liu Qian , Zhang Min , Liu Yuchao , Li Minhui
Published: September 2021

Xanthoceras sorbifolium Bunge (Sapindaceae) is a native Chinese plant with promising applications as a biofuel feedstock and a source of novel drugs. Historical records and documents from different periods have mentioned the use of X. sorbifolium and its botanical constituents in treating diseases, highlighting its central role in Chinese and Mongolian traditional medicinal therapies. Phytochemical research has focused on the husks, leaves, trunks, and branches of this herb. A total of 278 chemical compounds have been isolated and divided into 8 categories: triterpenoids, flavonoids, phenylpropanoids, steroids, phenols, fatty acids, alkaloids, and quinones. Modern pharmacological studies on X. sorbifolium have demonstrated positive effects on learning and memory, as well as anti-inflammatory, anti-tumor, and anti-oxidative properties. This review provides a comprehensive analysis of the available research on X. sorbifolium, focusing on the relationship between chemical constituents, traditional uses, and pharmacological effects. We also assess the potential for therapeutic and other applications of this plant in support of further research and development of X. sorbifolium.
Fat-1 Transgenic Mice With Augmented n3-Polyunsaturated Fatty Acids Are Protected From Liver Injury Caused by Acute-On-Chronic Ethanol Administration
Authors: Warner Jeffrey , Hardesty Josiah , Song Ying , Sun Rui , Deng Zhongbin , Xu Raobo , Yin Xinmin , Zhang Xiang , McClain Craig , Warner Dennis , Kirpich Irina
Published: September 2021

Alcohol-associated liver disease (ALD) is the leading cause of liver disease worldwide, and alcohol-associated hepatitis (AH), a severe form of ALD, is a major contributor to the mortality and morbidity due to ALD. Many factors modulate susceptibility to ALD development and progression, including nutritional factors such as dietary fatty acids. Recent work from our group and others showed that modulation of dietary or endogenous levels of n6-and n3-polyunsaturated fatty acids (PUFAs) can exacerbate or attenuate experimental ALD, respectively. In the current study, we interrogated the effects of endogenous n3-PUFA enrichment in a mouse model which recapitulates features of early human AH using transgenic fat-1 mice which endogenously convert n6-PUFAs to n3-PUFAs. Male wild type (WT) and fat-1 littermates were provided an ethanol (EtOH, 5% v/v)-containing liquid diet for 10 days, then administered a binge of EtOH (5 g/kg) by oral gavage on the 11th day, 9 h prior to sacrifice. In WT mice, EtOH treatment resulted in liver injury as determined by significantly elevated plasma ALT levels, whereas in fat-1 mice, EtOH caused no increase in this biomarker. Compared to their pair-fed controls, a significant EtOH-mediated increase in liver neutrophil infiltration was observed also in WT, but not fat-1 mice. The hepatic expression of several cytokines and chemokines, including Pai-1, was significantly lower in fat-1 vs WT EtOH-challenged mice. Cultured bone marrow-derived macrophages isolated from fat-1 mice expressed less Pai-1 and Cxcl2 (a canonical neutrophil chemoattractant) mRNA compared to WT when stimulated with lipopolysaccharide. Further, we observed decreased pro-inflammatory M1 liver tissue-resident macrophages (Kupffer cells, KCs), as well as increased liver T regulatory cells in fat-1 vs WT EtOH-fed mice. Taken together, our data demonstrated protective effects of endogenous n3-PUFA enrichment on liver injury caused by an acute-on-chronic EtOH exposure, a paradigm which recapitulates human AH, suggesting that n3-PUFAs may be a viable nutritional adjuvant therapy for this disease.
Hordenine Protects Against Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting Inflammation
Authors: Zhang Xiyue , Du Li , Zhang Jinrong , Li Chunyan , Zhang Jie , Lv Xuejiao
Published: September 2021

Acute lung injury (ALI) is a respiratory disease that leads to death in severe cases. Hordenine (Hor), a barley-derived natural product, has various biological activities, including anti-inflammatory, and anti-oxidation activities. We investigated the effect of Hor on lipopolysaccharide-induced ALI and its potential mechanism. The anti-inflammatory effects of Hor were detected using in vivo and in vitro models by enzyme-linked immunosorbent assay, real-time polymerase chain reaction, western blotting, and molecular docking simulations. Hor inhibited increases in the levels of inflammatory factors both in vivo and in vitro, and its anti-inflammatory effect inhibited activation of protein kinase B, nuclear factor-κB, and mitogen-activated protein kinase signaling. Hor alleviated lipopolysaccharide-induced ALI by inhibiting inflammatory cytokine increases in vivo and in vitro and shows potential for preventing inflammatory disease.
Glucose Metabolism Reprogramming of Regulatory T Cells in Concanavalin A-Induced Hepatitis
Authors: Huang Chen , Shen Yi , Shen Mengyi , Fan Xiaoli , Men Ruoting , Ye Tinghong , Yang Li
Published: September 2021

Autoimmune hepatitis (AIH) is an inflammatory liver disease caused by a dysregulated immune response. Although the pathogenesis of AIH remains unclear, impaired regulatory T cells (Tregs) have been considered a driver of AIH development. Unlike autoreactive T cells, Tregs mainly utilize oxidative phosphorylation (OXPHOS) as their energy supply. Elevated glycolysis has been reported to limit the suppressive functions of Tregs. However, whether glucose metabolism reprogramming in Tregs is involved in AIH etiology remains unknown. The aim of this study was to examine alternations in Treg numbers and functions in AIH patients and concanavalin A (Con A)-induced hepatitis, while exploring associations between impaired Tregs and glucose metabolism. The frequency of Tregs was decreased in the peripheral blood but increased in liver biopsies of AIH patients. Moreover, immunosuppressive therapy rescued circulating Tregs in AIH. In Con A-induced immune hepatitis, enhanced intrahepatic Treg accumulation was observed over time, accompanied by reduced splenic Treg numbers. To investigate whether functional impairment of Tregs occurs in AIH, Tregs were isolated from experimental AIH (EAH) model mice and normal controls and the former displayed downregulated mRNA levels of FOXP3, CTLA4, CD103, TIGIT, CD39, and CD73. EAH model-derived Tregs also produced fewer anti-inflammatory mediators (TGF-β and IL-35) than control Tregs. Moreover, enhanced glycolysis and reduced OXPHOS were found in Tregs from EAH model mice, as reflected by elevated levels of key glycolytic enzymes (HK2, PK-M2, and LDH-A) and a decreased ATP concentration. This study revealed a decreased peripheral Treg frequency and abnormal intrahepatic Treg infiltration in AIH. It is first reported that glucose metabolism reprogramming is associated with decreases and functional impairments in the Treg population, promoting AIH development. Targeting glucose metabolism may provide novel insights for the treatment of AIH.
CD226 Is Required to Maintain Megakaryocytes/Platelets Homeostasis in the Treatment of Knee Osteoarthritis With Platelet-Rich Plasma in Mice
Authors: Liu Yongming , Zhang Yuan , Zhang Jinxue , Ma Jingchang , Bian Ka , Wang Yuling , Xu Xuexue , Wu Shuwen , Cheng Kun , Zhang Yun , Ding Yong , Zhou Yong , Zhuang Ran
Published: September 2021

Platelet-rich plasma (PRP) is a platelet-based application used to treat osteoarthritis (OA) clinically. The co-stimulatory molecule CD226 is expressed in T cells, NK cells, and also platelets. However, exact effects of CD226 on platelets and whether its expression level influences PRP efficacy are largely unknown. Here, CD226fl/flPF4-Cre mice were obtained from mating CD226 fl/fl mice with PF4-Cre mice. Blood samples and washed platelets were collected from the mice eyeballs to undergo routine blood tests and transmission electron microscopy. Differentially expressed proteins were detected by iTRAQ-based proteomics analysis. Animal OA models were established through surgical destabilization of the medial meniscus (DMM) for C57BL/6 wildtype mice, followed by PRP injection to evaluate the effects of platelet CD226 on PRP efficacy. The results showed that deletion of platelet CD226 increased the number of megakaryocytes (MKs) in bone marrow (BM) but reduced MKs in spleen, combined with significantly decreased platelet amounts, α-granule secretion, and reduced immature platelets; indicating that absence of platelet CD226 may disrupt MK/platelet homeostasis and arrested platelet release from MKs. Sequencing analysis showed abnormal ribosomal functions and much downregulated proteins in the absence of platelet CD226. Autophagy-related proteins were also reduced in the CD226-absent MKs/platelets. Moreover, deletion of platelet CD226 diminished the protective effects of PRP on DMM-induced cartilage lesions in mice, and PDGF restored it. Therefore, deficiency of platelet CD226 inhibited platelet maturation, secretion, and normal ribosomal functions, which may lead to depressed PRP efficacy on OA, suggesting that CD226 is required to regulate platelet growth, functions, and its application.
Therapeutic Effects and Molecular Mechanisms of Bioactive Compounds Against Respiratory Diseases: Traditional Chinese Medicine Theory and High-Frequency Use
Authors: Wang Jing , Wu Qibiao , Ding Lu , Song Siyu , Li Yaxin , Shi Li , Wang Tan , Zhao Daqing , Wang Zeyu , Li Xiangyan
Published: September 2021

Respiratory diseases, especially the pandemic of respiratory infectious diseases and refractory chronic lung diseases, remain a key clinical issue and research hot spot due to their high prevalence rates and poor prognosis. In this review, we aimed to summarize the recent advances in the therapeutic effects and molecular mechanisms of key common bioactive compounds from Chinese herbal medicine. Based on the theories of traditional Chinese medicine related to lung diseases, we searched several electronic databases to determine the high-frequency Chinese medicines in clinical application. The active compounds and metabolites from the selected medicines were identified using the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) by analyzing oral bioavailability and drug similarity index. Then, the pharmacological effects and molecular mechanisms of the selected bioactive compounds in the viral and bacterial infections, inflammation, acute lung injury (ALI), chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, asthma, and lung cancer were summarized. We found that 31 bioactive compounds from the selected 10 common Chinese herbs, such as epigallocatechin-3-gallate (EGCG), kaempferol, isorhamnetin, quercetin, and β-sitosterol, can mainly regulate NF-κB, Nrf2/HO-1, NLRP3, TGF-β/Smad, MAPK, and PI3K/Akt/mTOR pathways to inhibit infection, inflammation, extracellular matrix deposition, and tumor growth in a series of lung-related diseases. This review provides novel perspectives on the preclinical study and clinical application of Chinese herbal medicines and their bioactive compounds against respiratory diseases.
Progress in Traditional Chinese Medicine Against Respiratory Viruses: A Review
Authors: Li Bao-Hong , Li Zhong-Yuan , Liu Miao-Miao , Tian Jing-Zhen , Cui Qing-Hua
Published: September 2021

Respiratory viruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV)-1, SARS-CoV-2, influenza A viruses, and respiratory syncytial virus, pose a serious threat to society. Based on the guiding principles of “holism” and “syndrome differentiation and treatment”, traditional Chinese medicine (TCM) has unique advantages in the treatment of respiratory virus diseases owing to the synergistic effect of multiple components and targets, which prevents drug resistance from arising. According to TCM theory, there are two main strategies in antiviral treatments, namely “dispelling evil” and “fu zheng”. Dispelling evil corresponds to the direct inhibition of virus growth and fu zheng corresponds to immune regulation, inflammation control, and tissue protection in the host. In this review, current progress in using TCMs against respiratory viruses is summarized according to modern biological theories. The prospects for developing TCMs against respiratory viruses is discussed to provide a reference for the research and development of innovative TCMs with multiple components, multiple targets, and low toxicity.
China Stroke Registry for Patients With Traditional Chinese Medicine (CASES-TCM): Rationale and Design of a Prospective, Multicenter, Observational Study
Authors: Feng Luda , Kong Lingbo , Dong Xinglu , Lai Xinxing , Zhang Dandan , Ren Beida , Liu Shen , Xie Xiaolong , Li Chuanpeng , Song Yuebo , Du Yawei , Cao Kegang , Zhang Chi , Gao Ying ,   On Behalf of the CASES-TCM Protocol Steering Group
Published: September 2021

Background: Given the complexity of stroke treatment and the current widespread use of traditional Chinese medicine (TCM) in the absence of robust, large, long-term effectiveness and safety studies, and the lack of nationwide epidemiology and clinical characteristics of patients with stroke receiving TCM treatment, the acquisition of data from longitudinal cohorts is essential. We intend to generate the major clinical characteristics of patients with stroke who receive TCM treatment and to investigate the effectiveness and safety of TCM in the Chinese population.

Methods: The China Stroke Registry for Patients with Traditional Chinese Medicine (CASES-TCM) study is a prospective, multicenter, observational disease registry aiming to register 20,000 hospitalized patients. Eligible adult patients with clearly diagnosed acute ischemic stroke or intracerebral hemorrhage within 7 days of symptom onset will be consecutively registered from 126 participating sites across China. Baseline data will be recorded, and all patients will be regularly followed up at 3, 6, 12, and 24 months after stroke onset. Collected data will be entered into a web-based system with high-level data security. The primary outcomes include the distribution of scores on the modified Rankin Scale at the 3-months follow-up, and recurrent stroke events within the 12-months follow-up.

Conclusion: To our knowledge, the CASES-TCM study is the first and largest nationwide registry to document comprehensive data on TCM treatment in patients with acute stroke. The findings of this study will be valuable to improve our knowledge about TCM treatment for patients with stroke and its subsequent outcomes in the actual clinical setting, consequently facilitating and standardizing the optimization of individualized interventions with TCM for stroke prevention and treatment in China.

Study registration: This study was registered with Clinicaltrials.gov (URL: https://clinicaltrials.gov/, Unique identifier: NCT04921397).
Experimental Evaluation of Miniature Impedance Board for Loosening Monitoring of the Threaded Pipe Connection
Authors: Liang Yabin , Chen Yixuan , Zhang Zuocai , Feng Qian
Published: September 2021

Electromechanical impedance (Electromechanical impedance)-based methods as potential nondestructive evaluation (NDT) techniques have been widely used in the field of structural health monitoring (SHM), especially for the civil, mechanical, and aerospace engineering fields. However, it is still difficult to apply in practical applications due to the limitations of the impedance measurement hardware, which is usually expensive, bulky, and heavy. In this paper, a small, lightweight, and low power consumption EMI-based structural health monitoring system combined with the low-cost miniature impedance board AD5933 was studied experimentally to investigate its quantifiable performance in impedance measurement and structural damage identification. At first, a simple impedance test with a free PZT patch was introduced to present the impedance calibration and measurement procedure of AD5933, and then its calibration performance was validated by comparing the signature with the one measured by a professional impedance analyzer (WK6500B). In order to further validate the feasibility and effectiveness of the AD5933 board in practical applications, a threaded pipe connection specimen was assembled in the laboratory and then connected with the AD5933 to acquire its impedance signatures under different loosening severities. The final results demonstrated that the impedance measured by the AD5933 show a good consistency with the measurements by the WK6500B, and the evaluation board could be successfully utilized for the loosening severities identification and quantitatively evaluation.
Study of Shear Behavior of Binary Mixtures by DEM Simulation of Biaxial Test in the Membrane Boundary Condition
Authors: Wu Kai , Sun Weichen , Ding Jianwen , Zhang Xiang , Liu Songyu
Published: September 2021

This paper aims to study the shear behavior of binary particles with irregular shapes by discrete element method simulations of the biaxial test in the membrane boundary condition. Binary particle samples are generated according to different volume fractions of coarse and fine particles. The deviatoric stress and volumetric strain curves are plotted to describe the contracting-dilatancy relationship of binary samples under shearing conditions. The anisotropy of the normal and tangential contact forces are explored by visualization of the orientation of contact forces to describe the evolution of micro structures of samples during the shearing process. Besides, the formations of the shear band are observed by the visualization of the newly generated contact force chains between particles. The research shows that the volume fraction of coarse particles and particle size ratio have significant influences on the shear behavior of binary particles both in macroscopic and microscopic points of view. Moreover, the increased volume fraction of coarse particles leads to a more difficult formation of a shear band.
Neurohumoral Cardiac Regulation: Optogenetics Gets Into the Groove
Authors: Scalco Arianna , Moro Nicola , Mongillo Marco , Zaglia Tania
Published: September 2021

The cardiac autonomic nervous system (ANS) is the main modulator of heart function, adapting contraction force, and rate to the continuous variations of intrinsic and extrinsic environmental conditions. While the parasympathetic branch dominates during rest-and-digest sympathetic neuron (SN) activation ensures the rapid, efficient, and repeatable increase of heart performance, e.g., during the “fight-or-flight response.” Although the key role of the nervous system in cardiac homeostasis was evident to the eyes of physiologists and cardiologists, the degree of cardiac innervation, and the complexity of its circuits has remained underestimated for too long. In addition, the mechanisms allowing elevated efficiency and precision of neurogenic control of heart function have somehow lingered in the dark. This can be ascribed to the absence of methods adequate to study complex cardiac electric circuits in the unceasingly moving heart. An increasing number of studies adds to the scenario the evidence of an intracardiac neuron system, which, together with the autonomic components, define a little brain inside the heart, in fervent dialogue with the central nervous system (CNS). The advent of optogenetics, allowing control the activity of excitable cells with cell specificity, spatial selectivity, and temporal resolution, has allowed to shed light on basic neuro-cardiology. This review describes how optogenetics, which has extensively been used to interrogate the circuits of the CNS, has been applied to untangle the knots of heart innervation, unveiling the cellular mechanisms of neurogenic control of heart function, in physiology and pathology, as well as those participating to brain–heart communication, back and forth. We discuss existing literature, providing a comprehensive view of the advancement in the understanding of the mechanisms of neurogenic heart control. In addition, we weigh the limits and potential of optogenetics in basic and applied research in neuro-cardiology.
Comparative Metabolomics of Fruits and Leaves in a Hyperdiverse Lineage Suggests Fruits Are a Key Incubator of Phytochemical Diversification
Authors: Schneider Gerald F. , Salazar Diego , Hildreth Sherry B. , Helm Richard F. , Whitehead Susan R.
Published: September 2021

Interactions between plants and leaf herbivores have long been implicated as the major driver of plant secondary metabolite diversity. However, other plant-animal interactions, such as those between fruits and frugivores, may also be involved in phytochemical diversification. Using 12 species of Piper, we conducted untargeted metabolomics and molecular networking with extracts of fruits and leaves. We evaluated organ-specific secondary metabolite composition and compared multiple dimensions of phytochemical diversity across organs, including richness, structural complexity, and variability across samples at multiple scales within and across species. Plant organ identity, species identity, and the interaction between the two all significantly influenced secondary metabolite composition. Leaves and fruit shared a majority of compounds, but fruits contained more unique compounds and had higher total estimated chemical richness. While the relative levels of chemical richness and structural complexity across organs varied substantially across species, fruit diversity exceeded leaf diversity in more species than the reverse. Furthermore, the variance in chemical composition across samples was higher for fruits than leaves. By documenting a broad pattern of high phytochemical diversity in fruits relative to leaves, this study lays groundwork for incorporating fruit into a comprehensive and integrative understanding of the ecological and evolutionary factors shaping secondary metabolite composition at the whole-plant level.
In situ Root Phenotypes of Cotton Seedlings Under Phosphorus Stress Revealed Through RhizoPot
Authors: Zhang Zichen , Zhu Lingxiao , Li Dongxiao , Wang Nan , Sun Hongchun , Zhang Yongjiang , Zhang Ke , Li Anchang , Bai Zhiying , Li Cundong , Liu Liantao
Published: September 2021

Phosphorus (P) deficiency is a common challenge in crop production because of its poor mobility through the soil. The root system plays a significant role in P absorption from the soil and is the initial indicator of low P levels. However, the phenotypic dynamics and longevity of cotton roots under P stress remain unknown. In this study, RhizoPot, an improvised in situ root observation device, was used to monitor the dynamics of root phenotypes of cotton seedlings under P-deficient (PD) and P-replete (PR) conditions. Low P stress reduced P absorption and accumulation in the roots, leading to low dry weight accumulation. Cotton seedlings responded to low P stress by increasing the number of lateral roots, specific root length, branch density, root length density, and length of root hairs. Additionally, the life span of root hairs was prolonged. Low P stress also reduced the average diameter of roots, promoted root extension, expanded the root coverage area, and increased the range of P acquisition. Principal component analysis revealed that the net root growth rate, root length density, root dry weight, P absorption efficiency, average root hair length, and taproot daily growth significantly influenced the cotton root architecture. Collectively, these results show that low P stress reduces the net growth rate of cotton seedling roots and restricts plant growth. Plants respond to P deficiency by extending the life span of root hairs and increasing specific root length and lateral root branch density. This change in root system architecture improves the adaptability of plants to low P conditions. The findings of this study may guide the selection of cotton varieties with efficient P utilization.
Unraveling the Genetic Basis of Fertility Restoration for Cytoplasmic Male Sterile Line WNJ01A Originated From Brassica juncea in Brassica napus
Authors: Yang Qian , Nong Xiaoyi , Xu Jize , Huang Fan , Wang Fang , Wu Jiangsheng , Zhang Chunyu , Liu Chao
Published: September 2021

Crosses that lead to heterosis have been widely used in the rapeseed (Brassica napus L.) industry. Cytoplasmic male sterility (CMS)/restorer-of-fertility (Rf) systems represent one of the most useful tools for rapeseed production. Several CMS types and their restorer lines have been identified in rapeseed, but there are few studies on the mechanisms underlying fertility restoration. Here, we performed morphological observation, map-based cloning, and transcriptomic analysis of the F2 population developed by crossing the CMS line WNJ01A with its restorer line Hui01. Paraffin-embedded sections showed that the sporogenous cell stage was the critical pollen degeneration period, with major sporogenous cells displaying loose and irregular arrangement in sterile anthers. Most mitochondrial electron transport chain (mtETC) complex genes were upregulated in fertile compared to sterile buds. Using bulked segregant analysis (BSA)-seq to analyze mixed DNA pools from sterile and fertile F2 buds, respectively, we identified a 6.25 Mb candidate interval where Rfw is located. Using map-based cloning experiments combined with bacterial artificial chromosome (BAC) clone sequencing, the candidate interval was reduced to 99.75 kb and two pentatricopeptide repeat (PPR) genes were found among 28 predicted genes in this interval. Transcriptome sequencing showed that there were 1679 DEGs (1023 upregulated and 656 downregulated) in fertile compared to sterile F2 buds. The upregulated differentially expressed genes (DEGs) were enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) lysine degradation pathway and phenylalanine metabolism, and the downregulated DEGs were enriched in cutin, suberine, and wax biosynthesis. Furthermore, 44 DEGs were involved in pollen and anther development, such as tapetum, microspores, and pollen wall development. All of them were upregulated except a few such as POE1 genes (which encode Pollen Ole e I allergen and extensin family proteins). There were 261 specifically expressed DEGs (9 and 252 in sterile and fertile buds, respectively). Regarding the fertile bud-specific upregulated DEGs, the ubiquitin–proteasome pathway was enriched. The top four hub genes in the protein–protein interaction network (BnaA09g56400D, BnaA10g18210D, BnaA10g18220D, and BnaC09g41740D) encode RAD23d proteins, which deliver ubiquitinated substrates to the 26S proteasome. These findings provide evidence on the pathways regulated by Rfw and improve our understanding of fertility restoration.
Cognitive Processes of ESL Learners in Pragmatic Role-Play Tasks in Academic Settings
Authors: Bi Nick Zhiwei
Published: September 2021

The purpose of the study was to investigate the cognitive processes of English as second language (L2) learners that are involved in their task-based pragmatic performances in academic settings. This study, therefore, examined the cognitive processes of 30 English L2 learners when engaging in various role-play-based pragmatic performances, such as requesting a recommendation letter from a professor and negotiating an agreeable meeting time with classmates. The qualitative analyses of the retrospective verbal reports (RVRs) data of the participants indicated that the learners employed a series of cognitive, metacognitive, and pragmatic strategies when accomplishing various speech acts (e.g., requests and refusals). This study hoped to make two new contributions to the field. First, the study provided empirical evidence to validate the theoretical taxonomy of the strategy use of learners in L2 pragmatics. Additionally, the theoretical foundations of current research on cognitive processes are primarily informed by pragmatic theories. Thus, the study aims to explicate a more comprehensive view of the cognitive processes of L2 learners in pragmatic performances by employing the theories from both pragmatic and learner strategy perspectives.
Cuteness or Coolness—How Does Different Anthropomorphic Brand Image Accelerate Consumers’ Willingness to Buy Green Products?
Authors: Lu Yue , Liu Yunxiao , Tao Le , Ye Shenghong
Published: September 2021

Green consumption is an important component of environmental protection behavior. The behaviors of individual consumers are having unprecedented impacts on the sustainable development of a green society. Previous research has discussed how anthropomorphic beneficiaries of environmental behavior (e.g., nature/earth) impact green consumption behavior and compared the influence of anthropomorphic presence and absence on consumers. However, few have examined the impact of different types of anthropomorphic carriers with environmental benefits (e.g., green product/brand) on consumers. This research explores the matching effects on the willingness of consumers to buy green products between the anthropomorphic image of the brand (cute vs. cool) and advertising appeals (self-interest vs. altruism); in addition, the underlying mechanisms of matching effects are revealed. The results show that, under the self-interested advertising appeal, the cool anthropomorphic image can lead to higher purchase intention of green products due to the mediating role played by the brand capacity trust. However, when exposed to altruistic advertising appeal, the cute anthropomorphic image can enhance brand goodwill trust of consumers and make consumers more willing to buy green products. Finally, this paper discusses the contributions and limitations.
Forced Remote Learning During the COVID-19 Pandemic in Germany: A Mixed-Methods Study on Students' Positive and Negative Expectations
Authors: Hoss Thomas , Ancina Amancay , Kaspar Kai
Published: September 2021

The COVID-19 pandemic poses great challenges to higher education. Universities had to change their infrastructure to full remote teaching and learning environments in a very short time. Lecturers and students were forced to adjust their established routines and concepts of teaching and learning. During the first nationwide lockdown in Germany, we explored students' anticipations regarding the risks and chances of this challenging situation. They were asked about the negative and positive effects of this sudden switch to online university courses and the relevance personally ascribed to each of these expected effects. A sample of 584 students provided 3,839 statements, which were examined by means of qualitative content analysis. While 57.7% of the statements concerned negative effects, 42.3% dealt with positive ones. The range of expected negative and positive effects was wide, but key themes emerged particularly frequently. While the mentioned effects were generally considered to be of high personal relevance, negative effects were rated as significantly more relevant, but with only a small effect size. The relevance of negative effects was considered higher by master students than by bachelor students. Relevance ratings were significantly higher for the first effect mentioned compared with all subsequent effects, indicating an ease-of-retrieval effect, which is relevant from both a methodological and content perspective. The results provide important insights into students' perspectives on remote learning that will be significant beyond the current pandemic, as they can guide sustainable measures by exploiting opportunities and mitigating risks. We discuss practical implications and methodological limitations of the study.
Observing the Working Alliance in Videoconferencing Psychotherapy for Alcohol Addiction: Reliability and Validity of the Working Alliance Inventory Short Revised Observer
Authors: Ribeiro Nathálya Soares , Colugnati Fernando Antonio Basile , Kazantzis Nikolaos , Sartes Laisa Marcorela Andreoli
Published: September 2021

The coronavirus disease-2019 (COVID-19) pandemic has affected the mental health and alcohol consumption of individuals. Videoconferencing psychotherapy has become a fundamental mode of treatment for people with alcohol use disorders. However, there are still doubts about its effectiveness and the therapeutic relationship. The working alliance is considered a foundation of effective practice in cognitive behavioral therapy (CBT). Observer measurements of the working alliance have demonstrated reliability and meaningful associations with the reduction of symptoms. However, translations of instruments to evaluate the working alliance and examine its construct have not previously been conducted for online psychotherapy for alcohol addiction. This study aimed for the cross-cultural adaptation of the Working Alliance Inventory-Short Form-Observer (WAI-SR-O) for Brazil and the evaluation of its reliability and evidence of its validity in videoconferencing psychotherapy for alcoholism. The WAI-SR-O was applied by pairs of observers for the evaluation of the working alliance in 19 recorded sessions of videoconferencing psychotherapy of 10 clients with a diagnosis of alcohol addiction. The sessions were also evaluated by the therapist (WAI-T) and client (WAI-C). The WAI-SR-O shows a moderate inter-rater intraclass correlation coefficient (ICC = 0.67) for the general scale, higher ICC for the goals and bond subscales, and a moderate value for the task subscale. The internal consistency was good (a = 0.86). The results show low but significant correlations among the goals and bond subscales of the WAI-SR-O and the general, goals, and bond scales of the WAI-T. No correlations were found with the WAI-C. As the literature points out, the client, therapist, and observer versions of the WAI evaluated the alliance differently, requiring further study. The WAI-SR-O proved to be a reliable and valid measurement for the evaluation of the working alliance in videoconferencing psychotherapy for alcohol addiction, becoming an important tool for the study of the working alliance in telepsychotherapy.
Mind-Wandering Mediates the Associations Between Neuroticism and Conscientiousness, and Tendencies Towards Smartphone Use Disorder
Authors: Müller Marko , Sindermann Cornelia , Rozgonjuk Dmitri , Montag Christian
Published: September 2021

Mounting evidence suggests that smartphone overuse/smartphone use disorder (SmUD) is associated with negative affectivity. Given a large number of smartphone users worldwide (currently about 4.7 billion) and the fact that many individuals carry their smartphones around 24/7, it is of high importance to better understand the phenomenon of smartphone overuse. Based on the interaction of person-affect-cognition-execution (I-PACE) model, we investigated the links between SmUD and the personality traits, neuroticism and conscientiousness, which represent two vulnerability factors robustly linked to SmUD according to a recent meta-analysis. Beyond that, we tested the effects of mind-wandering (MW) and fear of missing out (FoMO) in the relation between individual differences in personality and tendencies towards SmUD. The effective sample comprised 414 study participants (151 men and 263 women, age M = 33.6, SD = 13.5). By applying a structural equation modeling (SEM) technique, we observed that the associations of higher neuroticism and lower conscientiousness with higher levels of SmUD were mediated by higher scores in mind-wandering. These novel findings can help to understand the associations between personality and SmUD in more detail.