bluuebunny/crossref_metadata_2025 huggingface dataset:
AHL-Lactonase Producing Psychrobacter sp. From Palk Bay Sediment Mitigates Quorum Sensing-Mediated Virulence Production in Gram Negative Bacterial Pathogens
Authors: Packiavathy Issac Abraham Sybiya Vasantha , Kannappan Arunachalam , Thiyagarajan Sivaprakasam , Srinivasan Ramanathan , Jeyapragash Danaraj , Paul John Bosco John , Velmurugan Pazhanivel , Ravi Arumugam Veera
Published: April 2021

Quorum sensing (QS) is a signaling mechanism governed by bacteria used to converse at inter- and intra-species levels through small self-produced chemicals called N-acylhomoserine lactones (AHLs). Through QS, bacteria regulate and organize the virulence factors’ production, including biofilm formation. AHLs can be degraded by an action called quorum quenching (QQ) and hence QQ strategy can effectively be employed to combat biofilm-associated bacterial pathogenesis. The present study aimed to identify novel bacterial species with QQ potential. Screening of Palk Bay marine sediment bacteria for QQ activity ended up with the identification of marine bacterial isolate 28 (MSB-28), which exhibited a profound QQ activity against QS biomarker strain Chromobacterium violaceum ATCC 12472. The isolate MSB-28 was identified as Psychrobacter sp. through 16S-rRNA sequencing. Psychrobacter sp. also demonstrated a pronounced activity in controlling the biofilm formation in different bacteria and biofilm-associated virulence factors’ production in P. aeruginosa PAO1. Solvent extraction, heat inactivation, and proteinase K treatment assays clearly evidence the enzymatic nature of the bioactive lead. Furthermore, AHL’s lactone ring cleavage was confirmed with experiments including ring closure assay and chromatographic analysis, and thus the AHL-lactonase enzyme production in Psychrobacter sp. To conclude, this is the first report stating the AHL-lactonase mediated QQ activity from marine sediment bacteria Psychrobacter sp. Future work deals with the characterization, purification, and mass cultivation of the purified protein and should pave the way to assessing the feasibility of the identified protein in controlling QS and biofilm-mediated multidrug resistant bacterial infections in mono or multi-species conditions.
Analyses of Clinical and Biological Data for French and Belgian Immunocompetent Patients Infected With Hepatitis E Virus Genotypes 4 and 3
Authors: Micas Florence , Suin Vanessa , Péron Jean-Marie , Scholtes Caroline , Tuaillon Edouard , Vanwolleghem Thomas , Bocket Laurence , Lhomme Sébastien , Dimeglio Chloé , Izopet Jacques , Abravanel Florence
Published: April 2021

Hepatitis E virus (HEV) genotypes 3 and 4 are the major causes of acute hepatitis in industrialized countries. Genotype 3 is mainly found in Europe and America, while genotype 4 is predominant in Asia. Several Japanese studies have suggested that genotype 4 is more virulent than genotype 3. We investigated this aspect by analyzing the clinical and biological data for 27 French and Belgian immunocompetent patients infected with HEV genotype 4. Their infections were probably acquired locally, since none of these patients reported traveling outside France or Belgium during the 2–8 weeks before symptoms onset. Each patient was matched for age (±5 years) and gender with two patients infected with HEV genotype 3. Bivariate analysis indicated that the HEV genotype 4-infected patients had significantly higher alanine aminotransferase (ALT) (2067 IU/L) and aspartate aminotransferase (AST) (1581 IU/L) activities and total bilirubin concentrations (92.4 μmol/L) than did those infected with HEV genotype 3 (1566 IU/L, p = 0.016; 657 IU/L, p = 0.003 and 47 μmol/L, p = 0.046) at diagnosis. In contrast, more patients infected with HEV genotype 3 reported dark urine (71% vs. 39%, p = 0.02) and experienced asthenia (89% vs. 58%, p < 0.01) than did those infected with HEV genotype 4. Two HEV genotype 4-infected patients died of multi-organ failure, while none of the genotype 3-infected patients died (p = 0.035). Finally, stepwise regression analysis retained only a greater increase in ALT (odds-ratio: 1.0005, 95% confidence interval: 1.00012–1.00084) and less frequent fever (odds-ratio = 0.1244; 95% confidence interval: 0.01887–0.82020) for patients infected with HEV genotype 4. We conclude that HEV-4 infections are likely to be associated with higher ALT activity than HEV-3 infections. Additional immunological and virological studies are required to confirm these findings and better understand the influence, if any, of genotype on HEV pathophysiology.
Iron Deposition Characteristics of Deep Gray Matter in Elderly Individuals in the Community Revealed by Quantitative Susceptibility Mapping and Multiple Factor Analysis
Authors: Li Jing , Zhang Qihao , Che Yena , Zhang Nan , Guo Lingfei
Published: April 2021

Purpose

The objective of this study was to determine which factors influence brain iron concentrations in deep gray matter in elderly individuals and how these factors influence regional brain iron concentrations.

Methods

A total of 105 elderly individuals were enrolled in this study. All participants underwent detailed magnetic resonance imaging (MRI) examinations from October 2018 to August 2019. Among them, 44 individuals had undergone a previous MRI examination from July 2010 to August 2011. Quantitative susceptibility mapping (QSM) was utilized as an indirect quantitative marker of brain iron, and the susceptibility values of deep gray matter structures were obtained. Univariate analysis and multiple linear regression analysis were used to investigate 11 possible determinants for cerebral iron deposition.

Results

Our results showed no sex- or hemisphere-related differences in susceptibility values in any of the regions studied. Aging was significantly correlated with increased insusceptibility values in almost all analyzed brain regions (except for the thalamus) when we compared the susceptibility values at the two time points. In a cross-sectional analysis, the relationship between gray matter nucleus susceptibility values and age was conducted using Pearson’s linear regression. Aging was significantly correlated with the susceptibility values of the globus pallidus (GP), putamen (Put), and caudate nucleus (CN), with the Put having the strongest correlations. In multiple linear regression models, associations with increased susceptibility values were found in the CN, Put, red nucleus, and dentate nucleus for individuals with a history of type 2 diabetes mellitus (T2DM). However, the patients with hypertension showed significantly reduced susceptibility values in the red nucleus and dentate nucleus. Our data suggested that smokers had increased susceptibility values in the thalamus. No significant associations were found for individuals with a history of hypercholesterolemia and Apolipoprotein E4 carrier status.

Conclusion

Our data revealed that aging, T2DM, and smoking could increase iron deposition in some deep gray matter structures. However, hypertension had the opposite effects in the red nuclei and dentate nuclei. Brain iron metabolism could be influenced by many factors in different modes. In future studies, we should strictly control for confounding factors.
A Computational Framework for Controlling the Self-Restorative Brain Based on the Free Energy and Degeneracy Principles
Authors: Park Hae-Jeong , Kang Jiyoung
Published: April 2021

The brain is a non-linear dynamical system with a self-restoration process, which protects itself from external damage but is often a bottleneck for clinical treatment. To treat the brain to induce the desired functionality, formulation of a self-restoration process is necessary for optimal brain control. This study proposes a computational model for the brain's self-restoration process following the free-energy and degeneracy principles. Based on this model, a computational framework for brain control is established. We posited that the pre-treatment brain circuit has long been configured in response to the environmental (the other neural populations') demands on the circuit. Since the demands persist even after treatment, the treated circuit's response to the demand may gradually approximate the pre-treatment functionality. In this framework, an energy landscape of regional activities, estimated from resting-state endogenous activities by a pairwise maximum entropy model, is used to represent the pre-treatment functionality. The approximation of the pre-treatment functionality occurs via reconfiguration of interactions among neural populations within the treated circuit. To establish the current framework's construct validity, we conducted various simulations. The simulations suggested that brain control should include the self-restoration process, without which the treatment was not optimal. We also presented simulations for optimizing repetitive treatments and optimal timing of the treatment. These results suggest a plausibility of the current framework in controlling the non-linear dynamical brain with a self-restoration process.
Contralesional Structural Plasticity in Different Molecular Pathologic Subtypes of Insular Glioma
Authors: Huang Zhenxing , Li Gen , Li Zhenye , Sun Shengjun , Zhang Yazhuo , Hou Zonggang , Xie Jian
Published: April 2021

Neuroplasticity may preserve neurologic function in insular glioma, thereby improving prognosis following resection. However, the anatomic and molecular bases of this phenomenon are not known. To address this gap in knowledge, the present study investigated contralesional compensation in different molecular pathologic subtypes of insular glioma by high-resolution three-dimensional T1-weighted structural magnetic resonance imaging. A total of 52 patients with insular glioma were examined. We compared the gray matter volume (GMV) of the contralesional insula according to histological grade [low-grade glioma (LGG) and high-grade glioma (HGG)] and molecular pathology status [isocitrate dehydrogenase (IDH) mutation, telomerase reverse-transcriptase (TERT) promoter mutation, and 1p19q codeletion] by voxel-based morphometry (VBM). A cluster of 320 voxels in contralesional insula with higher GMV was observed in glioma with IDH mutation as compared to IDH wild-type tumors by region of interest-based VBM analysis (family-wise error-corrected at p < 0.05). The GMV of the entire contralesional insula was also larger in insular glioma patients with IDH mutation than in patients with wild-type IDH. However, there was no association between histological grade, TERT promoter mutation, or 1p19q codeletion and GMV in the contralesional insula. Thus, IDH mutation is associated with greater structural compensation in insular glioma. These findings may be useful for predicting neurocognitive and functional outcomes in patients undergoing resection surgery.
Independent Measures of Utricular Function: Ocular Vestibular Evoked Myogenic Potentials Do Not Correlate With Subjective Visual Vertical or Fundus Photographic Binocular Cyclorotation
Authors: Hösli Sarah , Straumann Dominik
Published: April 2021

Ocular vestibular evoked myogenic potentials (oVEMPs), subjective visual vertical (SVV), and fundus photographically measured binocular cyclorotation (BCR) are diagnostic tests to assess utricular function in patients with vertigo or dizziness. In 138 patients with chronic vertigo or dizziness, we asked whether the asymmetry ratio of oVEMP (normal, right side pathological, left side pathological) could predict the SVV deviation (normal, rightward deviation, leftward deviation) or BCR (normal, cyclorotation to the right, cyclorotation to the left). There was no correlation between oVEMP and SVV and between oVEMP and BCR, while SVV and BCR correlated highly. Although both oVEMP and SVV measure aspects of utricular function, our findings demonstrate that oVEMP and SVV are not redundant and may reflect different utricular pathologies. The role of fundus photographic BCR may be relegated to only confirm unclear SVV results in vestibular diagnostic workup.
Social Cognition in Neurodevelopmental Disorders and Epilepsy
Authors: Pastorino Grazia Maria Giovanna , Operto Francesca Felicia , Padovano Chiara , Vivenzio Valentina , Scuoppo Chiara , Pastorino Nazareno , Roccella Michele , Vetri Luigi , Carotenuto Marco , Coppola Giangennaro
Published: April 2021

Introduction: The purpose of our study was to perform a comparative analysis of social cognition in children and adolescents with epilepsy, autism spectrum disorder (ASD), specific learning disorder (SLD) and in typical development (TD) controls. The secondary aim was to relate social cognition to some clinical and demographic characteristics.

Methods: Our work is a transversal observational study. The recruits were 179 children and adolescents aged between 6 and 18 years diagnosed with epilepsy, ASD, or SLD and 32 subjects with TD. All the participants underwent neuropsychological assessment of Emotion Recognition (ER) and Theory of Mind (ToM) skills.

Results: All three clinical groups performed significantly worse than controls in ER and ToM. The ASD group achieved significantly lower performance than the other groups; however, the scores of SLD and epilepsy groups were comparable. The ER performances are related to non-verbal intelligence only in the group with epilepsy.

Conclusion: Children and adolescents with focal epilepsy, SLD, or ASD may present a deficit of varying extent in emotion recognition and ToM, compared with TD peers. These difficulties are more pronounced in individuals with ASD, but impairment worthy of clinical attention also emerges in individuals with SLD and epilepsy.
Working Memory Training Effects on White Matter Integrity in Young and Older Adults
Authors: Dziemian Sabine , Appenzeller Sarah , von Bastian Claudia C. , Jäncke Lutz , Langer Nicolas
Published: April 2021

Objectives

Working memory is essential for daily life skills like reading comprehension, reasoning, and problem-solving. Healthy aging of the brain goes along with working memory decline that can affect older people’s independence in everyday life. Interventions in the form of cognitive training are a promising tool for delaying age-related working memory decline, yet the underlying structural plasticity of white matter is hardly studied.

Methods

We conducted a longitudinal diffusion tensor imaging study to investigate the effects of an intensive four-week adaptive working memory training on white matter integrity quantified by global and tract-wise mean diffusivity. We compared diffusivity measures of fiber tracts that are associated with working memory of 32 young and 20 older participants that were randomly assigned to a working memory training group or an active control group.

Results

The behavioral analysis showed an increase in working memory performance after the four-week adaptive working memory training. The neuroanatomical analysis revealed a decrease in mean diffusivity in the working memory training group after the training intervention in the right inferior longitudinal fasciculus for the older adults. There was also a decrease in mean diffusivity in the working memory training group in the right superior longitudinal fasciculus for the older and young participants after the intervention.

Conclusion

This study shows that older people can benefit from working memory training by improving their working memory performance that is also reflected in terms of improved white matter integrity in the superior longitudinal fasciculus and the inferior longitudinal fasciculus, where the first is an essential component of the frontoparietal network known to be essential in working memory.
Spatial-Temporal Functional Mapping Combined With Cortico-Cortical Evoked Potentials in Predicting Cortical Stimulation Results
Authors: Wang Yujing , Hays Mark A. , Coogan Christopher , Kang Joon Y. , Flinker Adeen , Arya Ravindra , Korzeniewska Anna , Crone Nathan E.
Published: April 2021

Functional human brain mapping is commonly performed during invasive monitoring with intracranial electroencephalographic (iEEG) electrodes prior to resective surgery for drug­ resistant epilepsy. The current gold standard, electrocortical stimulation mapping (ESM), is time ­consuming, sometimes elicits pain, and often induces after discharges or seizures. Moreover, there is a risk of overestimating eloquent areas due to propagation of the effects of stimulation to a broader network of language cortex. Passive iEEG spatial-temporal functional mapping (STFM) has recently emerged as a potential alternative to ESM. However, investigators have observed less correspondence between STFM and ESM maps of language than between their maps of motor function. We hypothesized that incongruities between ESM and STFM of language function may arise due to propagation of the effects of ESM to cortical areas having strong effective connectivity with the site of stimulation. We evaluated five patients who underwent invasive monitoring for seizure localization, whose language areas were identified using ESM. All patients performed a battery of language tasks during passive iEEG recordings. To estimate the effective connectivity of stimulation sites with a broader network of task-activated cortical sites, we measured cortico-cortical evoked potentials (CCEPs) elicited across all recording sites by single-pulse electrical stimulation at sites where ESM was performed at other times. With the combination of high gamma power as well as CCEPs results, we trained a logistic regression model to predict ESM results at individual electrode pairs. The average accuracy of the classifier using both STFM and CCEPs results combined was 87.7%, significantly higher than the one using STFM alone (71.8%), indicating that the correspondence between STFM and ESM results is greater when effective connectivity between ESM stimulation sites and task-activated sites is taken into consideration. These findings, though based on a small number of subjects to date, provide preliminary support for the hypothesis that incongruities between ESM and STFM may arise in part from propagation of stimulation effects to a broader network of cortical language sites activated by language tasks, and suggest that more studies, with larger numbers of patients, are needed to understand the utility of both mapping techniques in clinical practice.
A Multisensory fMRI Investigation of Nociceptive-Preferential Cortical Regions and Responses
Authors: Zhang Xiaoxia , Li Linling , Huang Gan , Zhang Li , Liang Zhen , Shi Li , Zhang Zhiguo
Published: April 2021

The existence of nociceptive-specific brain regions has been a controversial issue for decades. Multisensory fMRI studies, which examine fMRI activities in response to various types of sensory stimulation, could help identify nociceptive-specific brain regions, but previous studies are limited by sample size and they did not differentiate nociceptive-specific regions and nociceptive-preferential regions, which have significantly larger responses to nociceptive input. In this study, we conducted a multisensory fMRI experiment on 80 healthy participants, with the aim to determine whether there are certain brain regions that specifically or preferentially respond to nociceptive stimulation. By comparing the evoked fMRI responses across four sensory modalities, we found a series of brain regions specifically or preferentially involved in nociceptive sensory input. Particularly, we found different parts of some cortical regions, such as insula and cingulate gyrus, play different functional roles in the processing of nociceptive stimulation. Hence, this multisensory study improves our understanding of the functional integrations and segregations of the nociceptive-related regions.
The Association Between Folate and Alzheimer's Disease: A Systematic Review and Meta-Analysis
Authors: Zhang Xiaohong , Bao Guangyi , Liu Debiao , Yang Yu , Li Xuezhi , Cai Gaomei , Liu Yan , Wu Yili
Published: April 2021

Alzheimer's disease (AD) is the most common type of neurodegenerative disease leading to dementia in the elderly. Increasing evidence indicates that folate plays an important role in the pathogenesis of AD. To investigate the role of folate deficiency/possible deficiency in the risk of AD and the benefical effect of sufficient folate intake on the prevention of AD, a systematic review and meta-analysis were performed. The Web of Science, PubMed, CENTRAL, EBSCO, CNKI, CQVIP, and Wanfang databases were searched. The analysis of cross-sectional studies showed that the standardized mean difference (SMD) was −0.60 (95% confidence interval (CI): −0.65, −0.55), indicating that plasma/serum folate level is lower in AD patients than that in controls. Moreover, the combined odds ratio (OR) of case-control studies was 0.96 (95% CI: 0.93, 0.99), while the combined ORs were 0.86 (95% CI: 0.46, 1.26) and 1.94 (95% CI: 1.02, 2.86) in populations with normal levels of folate (≥13.5 nmol/L) and folate deficiency/possible deficiency (<13.5 nmol/L), respectively. In addition, the risk ratio (RR) of the cohort studies was 1.88 (95% CI: 1.20, 2.57) in populations with folate deficiency/possible deficiency. Furthermore, when the intake of folate was equal to or higher than the recommended daily allowance, the combined RR and hazard ratio (HR) were 0.44 (95% CI: 0.18, 0.71) and 0.76 (95% CI: 0.52, 0.99), respectively. These results indicate that folate deficiency/possible deficiency increases the risk for AD, while sufficient intake of folate is a protective factor against AD.
Downregulating Long Non-coding RNAs CTBP1-AS2 Inhibits Colorectal Cancer Development by Modulating the miR-93-5p/TGF-β/SMAD2/3 Pathway
Authors: Li Qiankun , Yue Wenjing , Li Ming , Jiang Zhipeng , Hou Zehui , Liu Wei , Ma Ning , Gan Wenchang , Li Yingru , Zhou Taicheng , Yue Wenjing , Chen Shuang
Published: April 2021

Background: Colorectal cancer (CRC), the most commonly diagnosed cancer in the world, has a high mortality rate. In recent decades, long non-coding RNAs (lncRNAs) have been proven to exert an important effect on CRC growth. However, the CTBP1-AS2 expression and function in CRC are largely unknown.

Materials and Methods: The CTBP1-AS2 and miR-93-5p expression in CRC and para-cancerous tissues was detected by reverse transcription-PCR. The expression of CTBP1-AS2, miR-93-5p and the transforming growth factor-beta (TGF-β)/small mothers against decapentaplegic 2/3 (SMAD2/3) pathway was selectively regulated to study the correlation between CTBP1-AS2 expression and prognosis of patients with CRC. CRC cell proliferation, apoptosis, and invasion were measured in vivo and in vitro. In addition, bioinformatics was applied to explore the targeting relationship between CTBP1-AS2 and miR-93-5p. The targeting binding sites between CTBP1-AS2 and miR-93-5p, as well as between miR-93-5p and TGF-β, were verified by the dual-luciferase reporter assay and the RNA immunoprecipitation experiment.

Results: Compared with normal para-cancerous tissues, CTBP1-AS2 was considerably overexpressed in CRC tissues and was closely associated with worse survival of patients with CRC. Functionally, gain and loss in experiments illustrated that CTBP1-AS2 accelerated CRC cell proliferation and invasion and inhibited cell apoptosis. Mechanistically, CTBP1-AS2 regulated the malignant phenotype of tumor cells through the TGF-β/SMAD2/3 pathway. Moreover, miR-93-5p, as an endogenous competitive RNA of CTBP1-AS2, attenuated the oncogenic effects mediated by CTBP1-AS2.

Conclusion: CTBP1-AS2 promotes the TGF-β/SMAD2/3 pathway activation by inhibiting miR-93-5p, thereby accelerating CRC development.
Accessibility Considerations in the National Children's Study
Authors: Harniss Mark , Magasi Susan , Sabat Dianne
Published: April 2021

In the National Children's Study (NCS), assessments were proposed and developed that used a wide range of modes of administration (e.g., direct in-person interviews, telephone interviews, computer assisted interviews, self-administered questionnaires, real time and recall observations, and physical examinations). These modes of administration may pose accessibility challenges for some people with disabilities. Accessibility of measurement is important to consider because systematic exclusion of people with disabilities from research can lead to measurement bias and systematic error in derived scores. We describe our approach to analyzing the accessibility of measures in the NCS and describe the work of the Accessibility Domain Team. Finally, we describe a decision process for creating and using accessible health research measures.
Dehydrocostus Lactone Attenuates the Senescence of Nucleus Pulposus Cells and Ameliorates Intervertebral Disc Degeneration via Inhibition of STING-TBK1/NF-κB and MAPK Signaling
Authors: Chen Zhiqian , Yang Xiao , Zhou Yifan , Liang Zhihao , Chen Chen , Han Chen , Cao Xiankun , He Wenxin , Zhang Kai , Qin An , Zhou Tangjun , Zhao Jie
Published: April 2021

The progression of intervertebral disc degeneration (IDD) is multifactorial with the senescence of nucleus pulposus (NP) cells and closely related to inflammation in NP cells. Dehydrocostus lactone (DHE) is a natural sesquiterpene lactone isolated from medicinal plants that has anti-inflammatory properties. Thus, DHE may have a therapeutic effect on the progression of IDD. In this study, NP cells were used to determine the appropriate concentration of DHE in vitro. The role of DHE in tumor necrosis factor-α (TNF-α)–induced activation of inflammatory signaling pathways and cellular senescence, together with anabolism and catabolism of extracellular matrix (ECM) in NP cells, was examined in vitro. The therapeutic effect of DHE in vivo was determined using a spinal instability model of IDD in mice. The TNF-α–induced ECM degradation and the senescence of NP cells were partially attenuated by DHE. Mechanistically, DHE inhibited the activation of NF-κB and MAPK inflammatory signaling pathways and ameliorated the senescence of NP cells caused by the activation of STING-TBK1/NF-κB signaling induced by TNF-α. Furthermore, a spinal instability model in mice demonstrated that DHE treatment could ameliorate progression of IDD. Together, our findings indicate that DHE can alleviate IDD changes and has a potential therapeutic function for the treatment of IDD.
Inhibition of TMEM16A by Natural Product Silibinin: Potential Lead Compounds for Treatment of Lung Adenocarcinoma
Authors: Guo Shuai , Bai Xue , Liu Yufei , Shi Sai , Wang Xuzhao , Zhan Yong , Kang Xianjiang , Chen Yafei , An Hailong
Published: April 2021

Background: Effective anticancer therapy can be achieved by identifying novel tumor-specific drug targets and screening of new drugs. Recently, TMEM16A has been identified to be overexpressed in lung adenocarcinoma, and inhibitors of TMEM16A showed obvious antitumor efficacy.

Methods: YFP fluorescence quenching and whole-cell patch clamp experiments were used to explore the inhibitory effect of silibinin on TMEM16A. Molecular docking and site-directed mutagenesis were performed to confirm the binding sites of silibinin and TMEM16A. MTT assay, wound healing assay, and annexin-V assay were used to detect the effect of silibinin on cancer cell proliferation, migration, and apoptosis. shRNA was transfected into LA795 cells to knock down the expression of endogenous TMEM16A. Tumor xenograft mice combined with Western blot experiments reveal the inhibitory effect and mechanism of silibinin in vivo.

Results: Silibinin concentration dependently inhibited the whole-cell current of TMEM16A with an IC50 of 30.90 ± 2.10 μM. The putative binding sites of silibinin in TMEM16A were K384, R515, and R535. The proliferation and migration of LA795 cells were downregulated by silibinin, and the inhibition effect can be abolished by knockdown of the endogenous TMEM16A. Further, silibinin was injected to tumor xenograft mice which exhibited significant antitumor activity without weight loss. Finally, Western blotting results showed the mechanism of silibinin inhibiting lung adenocarcinoma was through apoptosis and downregulation of cyclin D1.

Conclusion: Silibinin is a novel TMEM16A inhibitor, and it can be used as a lead compound for the development of lung adenocarcinoma therapy drugs.
Cost-Effectiveness of Alirocumab for the Secondary Prevention of Cardiovascular Events after Myocardial Infarction in the Chinese Setting
Authors: Liang Zhe , Chen Qi , Wei Ruiqi , Ma Chenyao , Zhang Xuehui , Chen Xue , Fang Fang , Zhao Quanming
Published: April 2021

Background: Proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab reduce ischemic events; however, the cost-effectiveness remains uncertain. This study sought to evaluate its economic value in patients with myocardial infarction (MI) from the Chinese healthcare perspective.

Methods: A state-transition Markov model was developed to determine the cost-effectiveness of alirocumab for preventing recurrent MI, ischemic stroke and death. Preventative effect of the therapy was gathered from ODYSSEY OUTCOMES trial and absolute reduction of low-density lipoprotein cholesterol (LDL-C) in ODYSSEY EAST trial, respectively. The primary outcome was the incremental cost-effectiveness ratio (ICER), defined as incremental cost per quality-adjusted life-year (QALY) gained.

Results: Compared with statin monotherapy, the ICER of alirocumab therapy at its present discounted price [34,355 Chinese yuan (CNY) annually, 33% rebate] based on clinical follow-up efficacy was 1,613,997 CNY per QALY gained. A willingness-to-pay threshold of 212,676 CNY per QALY would be achieved when the annual cost of alirocumab was reduced by 88% from the full official price to 6071 CNY. The therapeutic effect evaluation estimated by the magnitude of LDL-C reduction was superior to the results of clinical follow-up, but this medication was still far from cost-effective. Multiple vulnerable subgroup analyses demonstrated that the ICER for patients with polyvascular disease in 3 vascular beds was 111,750 CNY per QALY gained.

Conclusion: Alirocumab is not cost-effective in general MI population based on current discounted price. High long-term costs of alirocumab may be offset by health benefit in patients with polyvascular disease (3 beds).
Neutrophil Elastase Induces Chondrocyte Apoptosis and Facilitates the Occurrence of Osteoarthritis via Caspase Signaling Pathway
Authors: Wang Ganyu , Jing Weiqiang , Bi Yuxuan , Li Yue , Ma Liang , Yang Hui , Zhang Yuankai
Published: April 2021

Osteoarthritis (OA) is the most common and prevalent chronic joint disorders in the elderly population across the globe, resulting in severe disability and impairment of quality of life. Existing treatment can only alleviate the symptoms and delay the progression of OA. Therefore, novel and effective therapeutics strategies for OA need to be developed. Our present study first found that neutrophil elastase (NE) was significantly increased in OA patients’ synovial fluid. Next, we examined the effect of neutrophil elastase (NE) on chondrocytes in vitro and in vivo. The results showed that NE suppressed cell proliferation, induced apoptosis and prevented cell migration in chondrocytes in vitro, accompanied by the elevation of intracellular ROS and calcium level. Moreover, NE enhanced the cleaved caspase-3 levels and disrupted the mitochondrial transmembrane potential balance. Meanwhile, chondrocytes apoptosis induced by NE can be alleviated by caspase inhibitor, zVAD-FMK and antioxidants, GSH. Besides, treatment of sivelestat, the inhibitor of NE, significantly reduced the pathological processes in OA model rats in vivo. The results of our study suggested that NE is an important factor in OA, which induces chondrocyte apoptosis and facilitates the occurrence of OA via caspase signaling pathway, and targeting the crucial signal centering around NE may be the potential therapies for OA.
Chaos in the Shimizu-Morioka Model With Fractional Order
Authors: Wei Zhangzhi , Zhang Xin
Published: April 2021

The investigation of dynamical behaviors for fractional-order chaotic systems is a new trend recently. This article is numerically concerned with the Shimizu-Morioka model with a fractional order. We find that chaos exists in the fractional-order model with order less than three by utilizing the fractional calculus techniques, and some phase diagrams are also constructed.
A Dual-Band Non-destructive Dielectric Measurement Sensor Based on Complementary Split-Ring Resonator
Authors: Wang Chen , Liu Xiaoming , Gan Lu , Cai Qing
Published: April 2021

A dual-band non-destructive dielectric constant sensor based on the complementary split ring resonators is presented. The resonators for both bands use the complementary split ring structure of different sizes. Numerical simulation demonstrates that the resonating frequency and quality factor is dependent on the variation of dielectric constant and loss tangent, making it a potential structure for dielectric measurement. To search for the optimal thickness for measurement, parametric study is conducted and the retrieval expressions are obtained for both bands. The measured results indicate an accuracy of 1.5% in comparison with the data in the literature. In addition, the effect of air gap has been analyzed, showing that it is an important error source and eliminating such effect can improve the measurement accuracy.
Perceived Self-Control Effort, Subjective Vitality, and General Affect in an Associative Structure
Authors: Bertrams Alex
Published: April 2021

A crucial assumption of the recently developed schema model of self-control is that people’s perceived self-control efforts are related to the experience of lowered subjective vitality. In the present study, this assumption was tested. It was also examined whether perceived self-control effort is related to a diffuse affective experience (i.e., subjective vitality, general positive affect, and general negative affect as a combined factor) or is discretely related to subjective vitality, general positive affect, and general negative affect. Based on the previous literature, it was expected that the latter would better fit the data. In a survey study, university students (N = 501) completed standardized measures of their perceived self-control effort, subjective vitality, general positive affect, and general negative affect with regard to a specific frame of reference (i.e., during the current day and the last 2 days). Bivariate correlations and confirmatory factor analyses revealed the expected relationships, meaning that perceived self-control effort was negatively related to subjective vitality and that the statistical model with three distinct affective variables fit the data better than the model with subjective vitality, positive affect, and negative affect incorporated into one common factor. It was concluded that the findings are in line with the schema model of self-control.
Two Ends of the Leash: Relations Between Personality of Shelter Volunteers and On-leash Walking Behavior With Shelter Dogs
Authors: Shih Hao-Yu , Paterson Mandy B. A. , Georgiou Fillipe , Mitchell Leander , Pachana Nancy A. , Phillips Clive J. C.
Published: April 2021

Human personality influences the way people interact with dogs. This study investigated the associations between the personality of animal shelter volunteers and behavior during on-leash walks with shelter dogs. Video recording and a canine leash tension meter were used to monitor the on-leash walking. Personality was measured in five dimensions (neurotic, extroverted, open, agreeable and conscientious) with the NEO Five-Factor Inventory (NEO-FFI). Neurotic volunteers pulled the leash harder and tended to interact with dogs using more body language; dogs being walked by neurotic volunteers in turn displayed more lip-licking and body shaking and were more likely to be rated as well-behaved. Extroverted volunteers were associated with stronger maximal leash tension at both the human and dog ends of the leash, and they praised the dog more, often in a high pitched voice. These volunteers eliciting more tail-wagging and body shaking by the dog. Extroverted volunteers were also more tolerant of different dog behaviors. Volunteers with personalities characterized by “openness to experiences” were less likely to verbally attract the attention of dogs, praise dogs and talk to them in a high-pitched voice; however, dogs walked by these volunteers were more likely to pull on the leash, and engaged in more lip-licking but less sniffing. “Agreeable” volunteers liked to verbally attract the attention of the dogs and more commonly initiated hand gestures and physical contact, causing the dogs to pull less frequently; dogs in these dyads displayed more gazing and lip-licking behaviors. Conscientious volunteers were less likely to pull the leash and tended to have more physical contact with the dogs but did not favor verbal communication and did not use a high pitched voice.
Doomsday Prepping During the COVID-19 Pandemic
Authors: Smith Nina , Thomas Susan Jennifer
Published: April 2021

“Doomsday prepping” is a phenomenon which involves preparing for feared societal collapse by stockpiling resources and readying for self-sufficiency. While doomsday prepping has traditionally been reported in the context of extremists, during the COVID-19 pandemic, excessive stockpiling leading to supply shortages has been reported globally. It is unclear what psychological or demographic factors are associated with this stockpiling. This study investigated doomsday prepping beliefs and behaviors in relation to COVID-19 proximity, demographics, coping strategies, psychopathology, intolerance of uncertainty (IU), and personality in 384 participants (249 female) in an online study. Participants completed a number of questionnaires including the Post-Apocalyptic and Doomsday Prepping Beliefs Scale and a scale designed for the current study to measure prepping in the context of COVID-19. These were analyzed using ANOVAs, correlational, and mediation analyses to examine relationships between psychometric variables and stockpiling. Prepping beliefs and behaviors were higher in males than females and positively associated with anxiety, obsessive-compulsive symptoms, IU, and traditional masculinity traits. Older age, male gender, obsessive-compulsive symptoms, and traditional masculinity predicted unique variance in prepping. The relationship between gender and stockpiling was mediated by social learning (witnessing other people panic buying) and the perceived threat of COVID-19 (doomsday interpretations) while proximity and personal vulnerability to COVID-19 were non-significant. Results indicate that panic buying was influenced more by witnessing others stockpiling, personality, and catastrophic thinking rather than by proximity to danger. Education could target these factors in ongoing waves of the pandemic or future catastrophes.
Psychological Impact of COVID-19 Pandemic Among the General Population in Jordan
Authors: Khatatbeh Moawiah , Khasawneh Aws , Hussein Hasan , Altahat Omar , Alhalaiqa Fadwa
Published: April 2021

Objective: Pandemics are claimed to result in certain stressors. However, the potential psychological impact of a pandemic is often overlooked. The current study aimed to assess the psychological impact of the COVID-19 pandemic on Jordanians and to evaluate the influence of the socio-demographic variables on this impact.

Method: The current study employed a descriptive cross-sectional design using the Impact of Event Scale—Revised (IES-R) via a web-based questionnaire. The researchers utilized convenience sampling which led to a total of 2,854 participants from the 12 governorates of Jordan.

Results: The average score of the participants' responses on the IES-R questionnaire turned out to be 22.5 ± 11.7. Females were found to have more than double the odds of having an increased IES-R score [odds ratio (OR) = 2.2, confidence interval (CI) = 1.76–2.67] and participants who were older than 65 years had triple the odds of having the same risk compared to young adults aged 18–25 years (OR = 3.1, CI = 1.3–7.4). Significantly, having a family member diagnosed with COVID-19 placed individuals at a 7-fold higher risk of having an increased IRS-R score compared to their counterparts who did not have a family member diagnosed with COVID-19 (OR = 7, CI = 3.7–13.3).

Conclusion: COVID-19 pandemic has imposed significant level of psychological burden on Jordanians, especially among females. Governments should collaborate with psychiatrists, mental health professionals and local institutions to offer high-quality, timely crisis-oriented psychological services to the affected individuals for the duration of the COVID-19 pandemic.
The Value of Companion Dogs as a Source of Social Support for Their Owners: Findings From a Pre-pandemic Representative Sample and a Convenience Sample Obtained During the COVID-19 Lockdown in Spain
Authors: Bowen Jonathan , Bulbena Antonio , Fatjó Jaume
Published: April 2021

Dogs are a source of companionship and comfort for their owners, but the degree to which this might translate into real emotional and social support has not been quantified. Emotional and social support are essential to help people to get through personal crises such as bereavement. In this study we characterize the social support owners obtain from their dogs, provide evidence of how widespread this social support is amongst dog-owners, and show how social support from dogs can increase during a crisis (using the COVID-19 pandemic as an example). We collected data from a representative population-based sample of Spanish dog-owners and found that most respondents said that their dogs helped them to get through tough times. They got comfort from physical contact with their dogs, shared activities with them and treated them as confidants in a similar way to friends and family. These are all key aspects of social support, and dogs offer the advantage of being more available than human sources of support. It would be expected that the support that dogs provide would be increased during a time of personal crisis and when we looked at data collected from a convenience sample of Spanish dog-owners during the COVID-19 confinement that is what we found; during the confinement owners engaged in more shared activities with their dogs, hugged them more often and turned to them more as a source of companionship and comfort (p < 0.0001 in all cases). However, although owners did confide more in their dogs (p < 0.0001), the effect was not as great as for other aspects of social support. We suspect that this is because people were able to use telecommunications such as video conferencing to maintain their human confidant relationships. Our findings indicate that dogs can substitute for humans as sources of some kinds of social support when conventional sources are unavailable. Our conclusion is that where a dog is present in a household, it should be regarded as an important resource for social support. This should be considered when designing clinical interventions and when public health decisions are being made.
Epidemiological and Clinical Characteristics of COVID-19: A Retrospective Multi-Center Study in Pakistan
Authors: Ahmad Mehmood , Beg Bilal Mahmood , Majeed Arfa , Areej Sadaf , Riffat Sualeha , Rasheed Muhammad Adil , Mahmood Sammina , Mushtaq Rana Muhammad Zahid , Hafeez Mian Abdul
Published: April 2021

The emergence of a pathogen responsible for a mysterious respiratory disease was identified in China and later called a novel coronavirus. This disease was named COVID-19. The present study seeks to determine the epidemiological and clinical characteristics of COVID-19 in Pakistan. This report will exhibit a linkage between epidemiology and clinical aspects which in turn can be helpful to prevent the transmission of the virus in Pakistan. A retrospective, multiple center study was performed by collecting the data from patients' with their demographics, epidemiological status, history of co-morbid conditions, and clinical manifestations of the disease. The data was collected from 31 public-sector and 2 private hospitals across Pakistan by on-field healthcare workers. A Chi-square test was applied to assess the relationship between categorical data entries. A total of 194 medical records were examined. The median age of these patients was found to be 34 years. A total of 53.6% active cases were present including 41.2% males and 12.4% females till the end of the study. Adults accounted for most of the cases (94.3%) of COVID-19. Fever (86.60%), cough (85.05%), fatigue (36.60%), dyspnea (24.74%), and gastrointestinal discomfort (10.31%) were among the most frequently reported signs and symptoms by the patients. However, 4.12% of the total patient population remained asymptomatic. The median duration of hospital stay was found to be 14 (0–19) days. The earliest source of the spread of the virus may be linked to the foreigners traveling to Pakistan. Spread among men was more as compared to women. A few cases were found to be positive, due to the direct contact with pets or livestock. Hypertension (7.73%), diabetes (4.64%), cardiovascular conditions (2.58%) were the most common co-morbidities. The percentage mortality was 2.50% with the highest mortality among elders.
Understanding Panic Buying Through an Integrated Psychodynamic Lens
Authors: Cooper Marty A. , Gordon Jamie L.
Published: April 2021

Previous literature has identified panic buying as often being a response to environmental stressors. In early 2020, we saw an increase in panic buying as a response to a real and/or perceived lack of resources due to COVID-19. Although panic buying has a long history, there is a lack of literature to provide a psychological understanding of the phenomenon. During the early days of COVID-19 clients presented with fear and uncertainty. These negative emotions were, in part, a response to a real shortage of basic supplies. However, the panic response led to behaviors that, for some individuals, resulted in atypical buying patterns. From a therapeutic perspective, one can consider behavioral and psychodynamic explanations and interventions, and how this impacts the associated behaviors. This article will focus on psychodynamic understandings of panic buying as a response to events that result in negative emotions. By providing a psychodynamic understanding of panic buying, authors hope to contribute to the therapy of clients presenting with related behaviors and their associated negative affect.
The Promise of AI for DILI Prediction
Authors: Vall Andreu , Sabnis Yogesh , Shi Jiye , Class Reiner , Hochreiter Sepp , Klambauer Günter
Published: April 2021

Drug-induced liver injury (DILI) is a common reason for the withdrawal of a drug from the market. Early assessment of DILI risk is an essential part of drug development, but it is rendered challenging prior to clinical trials by the complex factors that give rise to liver damage. Artificial intelligence (AI) approaches, particularly those building on machine learning, range from random forests to more recent techniques such as deep learning, and provide tools that can analyze chemical compounds and accurately predict some of their properties based purely on their structure. This article reviews existing AI approaches to predicting DILI and elaborates on the challenges that arise from the as yet limited availability of data. Future directions are discussed focusing on rich data modalities, such as 3D spheroids, and the slow but steady increase in drugs annotated with DILI risk labels.