bluuebunny/crossref_metadata_2025 huggingface dataset:
Imaging Characteristics and Endovascular Treatment of Brain Arteriovenous Malformations Mainly Fed by the Posterior Cerebral Artery
Authors: Hou Kun , Li Chao , Su Han , Yu Jinlu
Published: January 2021

Background: A BAVM that is mainly supplied by the posterior cerebral artery (PCA) lies deeply in the middle of the bilateral posterior hemispheres. Few studies have investigated the imaging characteristics and endovascular treatment (EVT) of brain arteriovenous malformations (BAVMs) in this area.

Methods: A retrospective study was performed for patients who were diagnosed with PCA-BAVMs from January 2015 to December 2019. The PCA-BAVMs were divided into type I and type II according to their feeding arteries. Type I PCA-BAVMs were supplied by the posterior choroidal artery (PchA) from the PCA. They could be further subdivided into type Ia and type Ib. Type II PCA-BAVMs were supplied by the temporal or occipital branch from the PCA. They could also be further subdivided into type IIa and IIb. Targeted embolization of the risk factors was the main aim of EVT.

Results: Forty-two patients were identified, with age ranging from 6 to 63 years. Twenty-four cases belonged to type I (57.1%, 24/42), including 6 Ia cases and 18 Ib cases. Eighteen cases belonged to type II (42.9%, 18/42), including 7 IIa cases and 11 IIb cases. Immediate complete or nearly complete embolization was achieved in 17 (40.5%, 17/42) cases. Partial embolization was achieved in 25 (59.5%, 25/42) cases. Two (4.8%, 2/42) patients experienced intraoperative or postoperative bleeding. The GOS scores at discharge were 3, 4, and 5 in 2 (4.8%, 2/42), 2 (4.8%, 2/42), and 38 (90.4%, 38/42) cases, respectively. There was no statistical difference between patients in type I and type II groups regarding age, BAVM rupture, SM grade, immediate extent of obliteration, and prognosis. Deep venous drainage was more common in patients of the type I group (P < 0.001).

Conclusions: Our classification of the PCA-BAVMs was based on the segmentation of the PCA, which is a reasonable approach and could guide the strategy of EVT. EVT is a reasonable option for the PCA-BAVMs. The main aim of EVT is to secure the weak structures. A targeted EVT aimed at the ruptured part of the BAVM can reduce the risk of early rebleeding.
Retinal Microvascular Changes in Subtypes of Ischemic Stroke
Authors: Zhao Ying , Yang Bing , Xu An-Ding , Ruan Yi-Wen , Xu Ying , Hu Hui-Ling , Tan Ze-Feng
Published: January 2021

Aims: Retinal microvasculature shares prominent similarities with the brain vasculature. We aimed to assess the association between retinal microvasculature and subtypes of ischemic stroke.

Method: We consecutively enrolled ischemic stroke patients within 7 days of onset, who met the criteria of subtype of atherothrombosis (AT), small artery disease (SAD), or cardioembolism (CE) according to a modified version of the Trial of Org 10172 in Acute Stroke Treatment (NEW-TOAST). Digital fundus photographs were taken within 72 h of hospital admission using a digital camera (Topcon TRC-50DX), and fundus photographs were semi-automatically measured by software (Canvus 14 and NeuroLucida) for retinal vasculature parameters.

Results: A total of 141 patients were enrolled, including 72 with AT, 54 with SAD, and 15 with CE. AT subtype patients had the widest mean venular diameter within 0.5–1.0 disk diameter (MVD0.5−1.0DD) followed by SAD and CE subtypes (86.37 ± 13.49 vs. 83.55 ± 11.54 vs. 77.90 ± 8.50, respectively, P = 0.047); CE subtype patients had the highest mean arteriovenous ratio within 0.5–1.0 disk diameter (MAVR0.5−1.0DD) followed by the AT and SAD subtype groups (0.97 ± 0.03 vs. 0.89 ± 0.99 vs. 0.89 ± 0.11, respectively, P = 0.010); SAD subtype patients were found with the highest mean venular tortuosity within 0.0–2.0 disk diameter (MVT0.0−2.0DD) followed by the AT and CE subtypes (1.0294 ± 0.0081 vs. 1.0259 ± 0.0084 vs. 1.0243 ± 0.0066, respectively, P = 0.024). After adjusting for clinic characteristics, MVD0.5−1.0DD was significantly different among AT, SAD, and CE subtypes (P = 0.033). By receiver operating characteristic curve analysis, MVD0.5−1.0DD predicted the AT subtype (area 0.690, 95% confidence interval, 0.566–0.815), with a cutoff value of 82.23 μm (sensitivity 61.1%, specificity 73.3%).

Conclusion: Retinal MVD0.5−1.0DD (>82.23 μm) might be associated with the AT stroke subtype; however, we need large-scale prospective studies in future to explore the underlying mechanism and causal explanation for this finding.
Onabotulinumtoxin A Improves Psychological Aspects in Chronic Migraine Patients
Authors: Al-Hashel Jasem Youssef , Kh Ashkanani Hasan , Almutairi Ohood , Bokubar Fajer A. , Mubarak Shahad , Alwazzan Sawsan , Alroughani Raed , Youssry Doaa , Farouk Ahmed Samar
Published: January 2021

Background:Chronic migraine (CM) affects 5.4% of the Kuwaiti population. It is associated with significant headache-related disability, psychiatric comorbidity and reduced quality of life. The aim of this study is to assess the efficacy of Onabotulinumtoxin A on psychological aspects of chronic migraine patients.

Methods:This prospective study over 36 months included chronic migraine patients in a tertiary headache center. Eligible patients met International Classification of Headache Disorders disorders-third edition, beta version (ICHD-III) revision criteria for chronic migraine. Patients with history of psychiatric or medical problems other than migraine disorders were excluded. Patients who received less than 4 injections cycles of Onabotulinumtoxin A were excluded. Identified patients received 155 units of Onabotulinumtoxin A quarterly according to the Phase III Research Evaluating Migraine Prophylaxis Therapy Trail (PREEMPT) protocol. Quality of life, the seven-item Generalized Anxiety Disorder (GAD-7) scores, the nine-item Patient Health Questionnaire (PHQ9), and the Pittsburgh Sleep Quality Index (PSQI) were collected before injection and at the end of the study. Mean comparison tests were performed using the independent samplet-test to assess the effects of Onabotulinumtoxin A on quality of life and comorbid symptoms of anxiety, depression, and quality of sleep.

Results:The study identified 131 chronic migraine patients with a mean age of 44.92 years, mean disease duration of 12.20 years and a mean treatment sessions of 7.58. In their last visit, most of our sample showed improvement in quality of life (81%), GAD-7 (81%), PHQ9 (79%), and PSQ1 (76%). The mean score of patient satisfaction was 7.21. Onabotulinumtoxin A treatment for CM improved quality of life significantly (72.92 vs. 103.62; P< 0.0001). It was also associated with significant reduction in anxiety [GAD-7 (12.00 vs. 6.61; P< 0.0001)] and depression [PHQ-9 (17.91 vs. 12.52;P< 0.0001)] scores, as well as reduced difficulty in sleeping [PSQI (12.60 vs. 6.66;P< 0.0001)] at the last visit.

Conclusion:Prophylactic Onabotulinumtoxin A treatment for CM was associated with significant improvement of quality of life, reduction in symptoms of anxiety and depression, as well as improved symptoms of poor sleep.
Human-Centric Lighting: Foundational Considerations and a Five-Step Design Process
Authors: Houser Kevin W. , Esposito Tony
Published: January 2021

At its best, human-centric lighting considers the visual and non-visual effects of light in support of positive human outcomes. At its worst, it is a marketing phrase used to healthwash lighting products or lighting design solutions. There is no doubt that environmental lighting contributes to human health, but how might one practice human-centric lighting given both the credible potential and the implausible hype? Marketing literature is filled with promises. Technical lighting societies have summarized the science but have not yet offered design guidance. Meanwhile, designers are in the middle, attempting to distinguish credible knowledge from that which is dubious to make design decisions that affect people directly. This article is intended to: (1) empower the reader with fundamental understandings of ways in which light affects health; (2) provide a process for human-centric lighting design that can dovetail with the decision-making process that is already a part of a designer's workflow.
Acupuncture for Psychological Disorders Caused by Chronic Pain: A Review and Future Directions
Authors: Lin Lu-Lu , Li Hong-Ping , Yang Jing-Wen , Hao Xiao-Wan , Yan Shi-Yan , Wang Li-Qiong , Yu Fang-Ting , Shi Guang-Xia , Liu Cun-Zhi
Published: January 2021

Accumulating evidence supports an association between chronic pain and psychological disorders, a connection that seems to be bidirectional. Treating both the pain and psychological conditions together is essential for effective treatment outcomes. Acupuncture is a somatosensory-guided mind–body therapy that can tackle the multidimensional nature of pain with fewer or no serious adverse effects. In this review, we discuss the use of acupuncture in some conditions with a high incidence of psychological disorders caused by chronic pain: headache, musculoskeletal pain, low back pain, and cancer pain, focusing on the effect and potential mechanisms of acupuncture. Overall clinical studies indicated that acupuncture might effectively contribute to management of psychological disorders caused by chronic pain. Mechanistic studies showed that acupuncture significantly alleviated such psychological disorders by regulating the activity of amygdala and insula, and regulating functional connectivity of insular and limbic regions/medial prefrontal cortex in humans and the corresponding animal models. In addition, 5-HT in the dorsal raphe nucleus, opioid receptors in the cingulate cortex, and plasma met-enkephalin are involved in acupuncture relief of pain and psychological symptoms. Substantial evidences from animal and human research support a beneficial effect of acupuncture in psychological disorders caused by chronic pain.
Multi-Voiced Music Bypasses Attentional Limitations in the Brain
Authors: Barrett Karen Chan , Ashley Richard , Strait Dana L. , Skoe Erika , Limb Charles J. , Kraus Nina
Published: January 2021

Attentional limits make it difficult to comprehend concurrent speech streams. However, multiple musical streams are processed comparatively easily. Coherence may be a key difference between music and stimuli like speech, which does not rely on the integration of multiple streams for comprehension. The musical organization between melodies in a composition may provide a cognitive scaffold to overcome attentional limitations when perceiving multiple lines of music concurrently. We investigated how listeners attend to multi–voiced music, examining biological indices associated with processing structured versus unstructured music. We predicted that musical structure provides coherence across distinct musical lines, allowing listeners to attend to simultaneous melodies, and that a lack of organization causes simultaneous melodies to be heard as separate streams. Musician participants attended to melodies in a Coherent music condition featuring flute duets and a Jumbled condition where those duets were manipulated to eliminate coherence between the parts. Auditory–evoked cortical potentials were collected to a tone probe. Analysis focused on the N100 response which is primarily generated within the auditory cortex and is larger for attended versus ignored stimuli. Results suggest that participants did not attend to one line over the other when listening to Coherent music, instead perceptually integrating the streams. Yet, for the Jumbled music, effects indicate that participants attended to one line while ignoring the other, abandoning their integration. Our findings lend support for the theory that musical organization aids attention when perceiving multi–voiced music.
Novel Combination Therapies for the Treatment of Bladder Cancer
Authors: Peng Mei , Xiao Di , Bu Yizhi , Long Jiahui , Yang Xue , Lv Shuhe , Yang Xiaoping
Published: January 2021

Bladder cancer is the ninth most frequently diagnosed cancer world-wide and ranks 13th in cancer-related deaths. Two tremendous breakthroughs in bladder cancer therapy over the last decades are the approval of immune checkpoint inhibitors(ICIs)and the fibroblast growth factor receptor tyrosine kinase inhibitor (FGFR-TKI) erdafitinib for treating this deadly disease. Despite the beneficial effects of these approaches, the low response rate and the potential resistance of the cancer are major concerns. Hence, novel combination therapies to overcome these limitations have been investigated. In this context, combining immunotherapy with targeted drugs is an appealing therapeutic option to improve response and reduce the emergence of resistance in the management of bladder cancer. In this review, the rationale of using different therapeutic combinations is discussed according to the mechanistic differences, emphasizing the efficacy and safety based on evidence collected from preclinical and clinical studies. Finally, we highlight the limitations of these combinations and provide suggestions for further efforts in this challenging field.
Construction of Bone Metastasis-Specific Regulation Network Based on Prognostic Stemness-Related Signatures in Breast Invasive Carcinoma
Authors: Huang Runzhi , Li Zhenyu , Zhang Jiayao , Zeng Zhiwei , Zhang Jiaqi , Li Mingxiao , Wang Siqao , Xian Shuyuan , Xue Yuna , Chen Xi , Li Jie , Cheng Wenjun , Wang Bin , Yan Penghui , Yang Daoke , Huang Zongqiang
Published: January 2021

Background

Bone is the most common metastatic site of Breast invasive carcinoma (BRCA). In this study, the bone metastasis-specific regulation network of BRCA was constructed based on prognostic stemness-related signatures (PSRSs), their upstream transcription factors (TFs) and downstream pathways.

Methods

Clinical information and RNA-seq data of 1,080 primary BRCA samples (1,048 samples without bone metastasis and 32 samples with bone metastasis) were downloaded from The Cancer Genome Atlas (TCGA). The edgeR method was performed to identify differential expressed genes (DEGs). Next, mRNA stemness index (mRNAsi) was calculated by one-class logistic regression (OCLR). To analyze DEGs by classification, similar genes were integrated into the same module by weighted gene co-expression network analysis (WGCNA). Then, univariate and multivariate Cox proportional hazard regression were applied to find the PSRSs. Furthermore, PSRSs, 318 TFs obtained from Cistrome database and 50 hallmark pathways quantified by GSVA were integrated into co-expression analysis. Significant co-expression patterns were used to construct the bone metastasis-specific regulation network. Finally, spatial single-cell RNA-seq and chromatin immunoprecipitation sequence (ChIP-seq) data and multi-omics databases were applied to validate the key scientific hypothesis in the regulation network. Additionally, Connectivity Map (CMap) was utilized to select the potential inhibitors of bone metastasis-specific regulation network in BRCA.

Results

Based on edgeR and WGCNA method, 43 PSRSs were identified. In the bone metastasis-specific regulation network, MAF positively regulated CD248 (R = 0.435, P < 0.001), and hallmark apical junction was the potential pathway of CD248 (R = 0.353, P < 0.001). This regulatory pattern was supported by spatial single-cell RNA sequence, ChIP-seq data and multi-omics online databases. Additionally, alexidine was identified as the possible inhibitor for bone metastasis of BRCA by CMap analysis.

Conclusion

PSRSs played important roles in bone metastasis of BRCA, and the prognostic model based on PSRSs showed good performance. Especially, we proposed that CD248 was the most significant PSRS, which was positively regulated by MAF, influenced bone metastasis via apical junction pathway. And this axis might be inhibited by alexidine, which providing a potential treatment strategy for bone metastasis of BRCA.
Detecting Corticospinal Tract Impairment in Tumor Patients With Fiber Density and Tensor-Based Metrics
Authors: Fekonja Lucius S. , Wang Ziqian , Aydogan Dogu B. , Roine Timo , Engelhardt Melina , Dreyer Felix R. , Vajkoczy Peter , Picht Thomas
Published: January 2021

Tumors infiltrating the motor system lead to significant disability, often caused by corticospinal tract injury. The delineation of the healthy-pathological white matter (WM) interface area, for which diffusion magnetic resonance imaging (dMRI) has shown promising potential, may improve treatment outcome. However, up to 90% of white matter (WM) voxels include multiple fiber populations, which cannot be correctly described with traditional metrics such as fractional anisotropy (FA) or apparent diffusion coefficient (ADC). Here, we used a novel fixel-based along-tract analysis consisting of constrained spherical deconvolution (CSD)-based probabilistic tractography and fixel-based apparent fiber density (FD), capable of identifying fiber orientation specific microstructural metrics. We addressed this novel methodology’s capability to detect corticospinal tract impairment. We measured and compared tractogram-related FD and traditional microstructural metrics bihemispherically in 65 patients with WHO grade III and IV gliomas infiltrating the motor system. The cortical tractogram seeds were based on motor maps derived by transcranial magnetic stimulation. We extracted 100 equally distributed cross-sections along each streamline of corticospinal tract (CST) for along-tract statistical analysis. Cross-sections were then analyzed to detect differences between healthy and pathological hemispheres. All metrics showed significant differences between healthy and pathologic hemispheres over the entire tract and between peritumoral segments. Peritumoral values were lower for FA and FD, but higher for ADC within the entire cohort. FD was more specific to tumor-induced changes in CST than ADC or FA, whereas ADC and FA showed higher sensitivity. The bihemispheric along-tract analysis provides an approach to detect subject-specific structural changes in healthy and pathological WM. In the current clinical dataset, the more complex FD metrics did not outperform FA and ADC in terms of describing corticospinal tract impairment.
Bleeding in Critically Ill Children—Review of Literature, Knowledge Gaps, and Suggestions for Future Investigation
Authors: Aran Adi Avniel , Karam Oliver , Nellis Marianne E.
Published: January 2021

Clinically significant bleeding complicates up to 20% of admissions to the intensive care unit in adults and is associated with severe physiologic derangements, requirement for significant interventions and worse outcome. There is a paucity of published data on bleeding in critically ill children. In this manuscript, we will provide an overview of the epidemiology and characteristics of bleeding in critically ill children, address the association between bleeding and clinical outcomes, describe the current definitions of bleeding and their respective limitations, and finally provide an overview of current knowledge gaps and suggested areas for future research.
Comparative Efficacy and Safety of Chinese Herbal Injections Combined With Cyclophosphamide and 5-Fluorouracil Chemotherapies in Treatment of Breast Cancer: A Bayesian Network Meta-Analysis
Authors: Liu Shuyu , Wang Haojia , Wang Miaomiao , Hu Xiaohong , Yang Wenqian , Jin Ruiqi , Geng Yifei , Ni Mengwei , Wu Jiarui , Zhang Xiaomeng
Published: January 2021

Background: Given the limitations of chemotherapy for the treatment of breast cancer (BC) and the wide exploration of Chinese herbal injections (CHIs), this network meta-analysis (NMA) was conducted to analyze the comparative efficacy and safety of nine CHIs combined with CF (Cyclophosphamide and 5-Fluorouracil) chemotherapy regimens in the treatment of BC.

Methods: Several electronic databases were searched to identify randomized controlled trials (RCTs) from inception to January 6, 2020. RCTs were screened by pre-established eligibility criteria, and the quality of which was assessed using the Cochrane risk of bias tool. Outcomes such as the clinical effectiveness rate, performance status, peripheral hemogram, and detection of T-lymphocyte subsets were analyzed using the Winbugs 1.4.3 and Stata 13.0 software. Surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the examined treatments. Cluster analysis was performed to compare the effect of CHIs between two or three different outcomes.

Results: A total of 84 RCTs involving 7855 patients and nine CHIs were included. The results showed that compared to CF chemotherapy regimens alone, the ones injected along with Aidi, Shenmai, Shenqi Fuzheng, Kangai, Kanglaite, or Shengmai combined with CF can improve the clinical effectiveness rate. Aidi, Shenmai, Shenqi Fuzheng, Compound Kushen, Kangai, and Kanglaite injection combined with CF can improve the performance status. Shenqi Fuzheng injection was considered as a favorable choice for relieving adverse reactions. According to the results of cluster analysis, Aidi injection and Compound Kushen injection plus CF were more favorable for the clinical effectiveness rate and performance status.

Conclusion: In conclusion, Shenqi Fuzheng, Compound Kushen, Aidi, and Kangai injection combined with CF chemotherapy regimen have more significant effects for patients with BC. However, more high-quality clinical RCTs, especialy which correctly use blinding and allocation concealment, are required to support the conclusions.
Neuroprotective Studies on Polygonum hydropiper L. Essential Oils Using Transgenic Animal Models
Authors: Tong Xin , Li Xiaoling , Ayaz Muhammad , Ullah Farhat , Sadiq Abdul , Ovais Muhammad , Shahid Muhammad , Khayrullin Mars , Hazrat Ali
Published: January 2021

Polygonum hydropiperL. and related species are reported to possess neuroprotective potentials. In an attempt to validate its anti-Alzheimer’s potentials, leaf oils (Ph. Lo) were extensively evaluated in this study against severalin vitroandin vivomodels of Alzheimer’s disease. The Ph. Lo were tested against pathological targets of Alzheimer’s diseases (ADs). Thein vitroandin vivoassays were done for cholinesterase inhibition, anti-radical properties and cognitive assessments using transgenic animal models. In preliminary cholinesterase inhibition assays, Ph. Lo were more active against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2-azinobis (3-ethylbenzthiazoline)-6-sulfonic acid (ABTS), and hydrogen peroxide (H2O2) radicals. Subsequently, Ph. Lo was evaluated for its effects on special memory, exploratory behavior, and coordination using shallow water maze (SWM), Y-maze, open filed, and balance beam tests. Animal pre-genotyping was doneviapolymerase chain reaction (PCR) to confirm amyloid precursor protein (APP) transgene, and after completion of drug therapy, brain homogenates from the cortex and hippocampus were evaluated for cholinesterase and free radical studies. In SWM task, disease control animals treated with 10 mg/kg of Ph. Lo for 5 days exhibited significant improvement in cognitive performance indicated by low escape times on 5th day compared with normal animals. In the Y-maze test, transgenic animals showed higher spontaneous alternation behavior than disease control animals and standard control group animals. Ph. Lo therapy has improved the exploratory behavior and declined anxiety behavior in diseased animals as accessedviaopen field test. Ph. Lo administration significantly augmented the motor and coordination abilities of transgenic animals when compared to other groups of animals and declined AChE, BChE activities as well as free radicals load in the cortex and hippocampus tissues. Based on our finding, it is concluded that Ph. Lo exhibit significant neuroprotective potentials preliminary due to their anti-radicals and cholinesterase inhibitory activities. Ph. Lo need further detailed studies as potential aromatherapy against neurodegenerative disorders.
Chilean Rhubarb, Gunnera tinctoria (Molina) Mirb. (Gunneraceae): UHPLC-ESI-Orbitrap-MS Profiling of Aqueous Extract and its Anti-Helicobacter pylori Activity
Authors: Hebel-Gerber Sonja , García-Cancino Apolinaria , Urbina Angélica , Simirgiotis Mario J. , Echeverría Javier , Bustamante-Salazar Luis , Sáez-Carrillo Katia , Alarcón Julio , Pastene-Navarrete Edgar
Published: January 2021

The full UHPLC-MS metabolome fingerprinting and anti-Helicobacter pylori effect of Gunnera tinctoria (Molina) Mirb. (Nalca) total extract (GTE) and fractions prepared from its edible fresh petioles were evaluated. The activity of G. tinctoria against H. pylori strains ATCC 45504 and J99 was assessed in vitro by means of agar diffusion assay, Minimum Inhibition Concentration (MIC), and Minimum Bactericidal Concentration (MBC), while killing curve and transmission electronic microscopy (TEM) were conducted in order to determine the effect of the plant extract on bacterial growth and ultrastructure. Additionally, the inhibitory effect upon urease was evaluated using both the Jack Bean and H. pylori enzymes. To determine which molecules could be responsible for the antibacterial effects, tentative identification was done by ultra-high performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-Q-Orbitrap®-HR-MS). Furthermore, the total G. tinctoria extract was fractionated using centrifugal partition chromatography (CPC), giving four active fractions (1–4). It was determined that the crude extract and centrifugal partition chromatography fractions of G. tinctoria have a bactericidal effect being the lowest MIC and MBC = 32 μg/ml. In the killing curves, fraction one acts faster than control amoxicillin. In the urease assay, F3 exhibited the lowest IC50 value of 13.5 μg/ml. Transmission electronic microscopy showed that crude G. tinctoria extract promotes disruption and separation of the cellular wall and outer membrane detachment on H. pylori causing bacterial cell death.
Juglanin Inhibits Osteoclastogenesis in Ovariectomized Mice via the Suppression of NF-κB Signaling Pathways
Authors: Zhang Fangxue , Huang Xiaowei , Qi Yuhan , Qian Zhi , Ni Shuo , Zhong Zeyuan , Zhang Xu , Li Dejian , Yu Baoqing
Published: January 2021

Bone metabolism is a physiological process that involves both osteoblasts and osteoclasts. Pathological changes of osteoclasts are commonly seen in osteoporosis diseases. Juglanin is a natural compound, reported to have an inhibitory effect on inflammation, oxidative stress and cancer progression. The purpose of this study is to explore the role that Juglanin plays on the osteoclast functions and underlying signaling pathways. In vitro study demonstrated that Juglanin had negative influence on osteoclastic differentiation by suppressing the transcription activity of osteoclastogenesis-related genes and proteins. To determine the underlying mechanism, Western blot was employed to show that Juglanin could significantly have negative effect on the phosphorylation of P50, P65, I-κB， ultimately suppressing the expression and transcriptional activity of nuclear factor of activated T cells (NFATc1). In vivo Juglanin treatment attenuate bone reducing in mice with removed ovary through suppressing osteoclast functioning. Taken together, our study demonstrated that in the molecular mechanism, JUG inhibited the expression of receptor activator of nuclear factor-κ B ligand (RANKL) induced NF - κ B signaling pathway, thus may play a vital part in preventing postmenopausal osteoporosis.
The Heart of the Alzheimer's: A Mindful View of Heart Disease
Authors: Evangelisti Alessandro , Butler Helen , del Monte Federica
Published: January 2021

Purpose of Review: This review summarizes the current evidence for the involvement of proteotoxicity and protein quality control systems defects in diseases of the central nervous and cardiovascular systems. Specifically, it presents the commonalities between the pathophysiology of protein misfolding diseases in the heart and the brain.

Recent Findings: The involvement of protein homeostasis dysfunction has been for long time investigated and accepted as one of the leading pathophysiological causes of neurodegenerative diseases. In cardiovascular diseases instead the mechanistic focus had been on the primary role of Ca2+ dishomeostasis, myofilament dysfunction as well as extracellular fibrosis, whereas no attention was given to misfolding of proteins as a pathogenetic mechanism. Instead, in the recent years, several contributions have shown protein aggregates in failing hearts similar to the ones found in the brain and increasing evidence have highlighted the crucial importance that proteotoxicity exerts via pre-amyloidogenic species in cardiovascular diseases as well as the prominent role of the cellular response to misfolded protein accumulation. As a result, proteotoxicity, unfolding protein response (UPR), and ubiquitin-proteasome system (UPS) have recently been investigated as potential key pathogenic pathways and therapeutic targets for heart disease.

Summary: Overall, the current knowledge summarized in this review describes how the misfolding process in the brain parallels in the heart. Understanding the folding and unfolding mechanisms involved early through studies in the heart will provide new knowledge for neurodegenerative proteinopathies and may prepare the stage for targeted and personalized interventions.
COVID-19 Disease Course in Former Smokers, Smokers and COPD Patients
Authors: Alberca Ricardo Wesley , Lima Júlia Cataldo , Oliveira Emily Araujo de , Gozzi-Silva Sarah Cristina , Ramos Yasmim Álefe Leuzzi , Andrade Milena Mary de Souza , Beserra Danielle Rosa , Oliveira Luana de Mendonça , Branco Anna Cláudia Calvielli Castelo , Pietrobon Anna Julia , Pereira Nátalli Zanete , Teixeira Franciane Mouradian Emidio , Fernandes Iara Grigoletto , Duarte Alberto José da Silva , Benard Gil , Sato Maria Notomi
Published: January 2021

The severe respiratory and systemic disease named coronavirus disease-2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, the COVID-19 pandemic presents a huge social and health challenge worldwide. Many different risk factors are associated with disease severity, such as systemic arterial hypertension, diabetes mellitus, obesity, older age, and other co-infections. Other respiratory diseases such as chronic obstructive pulmonary disease (COPD) and smoking are common comorbidities worldwide. Previous investigations have identified among COVID-19 patients smokers and COPD patients, but recent investigations have questioned the higher risk among these populations. Nevertheless, previous reports failed to isolate smokers and COPD patients without other comorbidities. We performed a longitudinal evaluation of the disease course of smokers, former smokers, and COPD patients with COVID-19 without other comorbidities, from hospitalization to hospital discharge. Although no difference between groups was observed during hospital admission, smokers and COPD patients presented an increase in COVID-19-associated inflammatory markers during the disease course in comparison to non-smokers and former smokers. Our results demonstrated that smoking and COPD are risk factors for severe COVID-19 with possible implications for the ongoing pandemic.
Comparative Chloroplast Genomics of Corydalis Species (Papaveraceae): Evolutionary Perspectives on Their Unusual Large Scale Rearrangements
Authors: Xu Xiaodong , Wang Dong
Published: January 2021

The chloroplast genome (plastome) of angiosperms (particularly photosynthetic members) is generally highly conserved, although structural rearrangements have been reported in a few lineages. In this study, we revealed Corydalis to be another unusual lineage with extensive large-scale plastome rearrangements. In the four newly sequenced Corydalis plastomes that represent all the three subgenera of Corydalis, we detected (1) two independent relocations of the same five genes (trnV-UAC-rbcL) from the typically posterior part of the large single-copy (LSC) region to the front, downstream of either the atpH gene in Corydalis saxicola or the trnK-UUU gene in both Corydalis davidii and Corydalis hsiaowutaishanensis; (2) relocation of the rps16 gene from the LSC region to the inverted repeat (IR) region in Corydalis adunca; (3) uniform inversion of an 11–14 kb segment (ndhB-trnR-ACG) in the IR region of all the four Corydalis species (the same below); (4) expansions (>10 kb) of IR into the small single-copy (SSC) region and corresponding contractions of SSC region; and (5) extensive pseudogenizations or losses of 13 genes (accD, clpP, and 11 ndh genes). In addition, we also found that the four Corydalis plastomes exhibited elevated GC content in both gene and intergenic regions and high number of dispersed repeats. Phylogenomic analyses generated a well-supported topology that was consistent with the result of previous studies based on a few DNA markers but contradicted with the morphological character-based taxonomy to some extent. This study provided insights into the evolution of plastomes throughout the three Corydalis subgenera and will be of value for further study on taxonomy, phylogeny, and evolution of Corydalis.
Past and Future of Plant Stress Detection: An Overview From Remote Sensing to Positron Emission Tomography
Authors: Galieni Angelica , D'Ascenzo Nicola , Stagnari Fabio , Pagnani Giancarlo , Xie Qingguo , Pisante Michele
Published: January 2021

Plant stress detection is considered one of the most critical areas for the improvement of crop yield in the compelling worldwide scenario, dictated by both the climate change and the geopolitical consequences of the Covid-19 epidemics. A complicated interconnection of biotic and abiotic stressors affect plant growth, including water, salt, temperature, light exposure, nutrients availability, agrochemicals, air and soil pollutants, pests and diseases. In facing this extended panorama, the technology choice is manifold. On the one hand, quantitative methods, such as metabolomics, provide very sensitive indicators of most of the stressors, with the drawback of a disruptive approach, which prevents follow up and dynamical studies. On the other hand qualitative methods, such as fluorescence, thermography and VIS/NIR reflectance, provide a non-disruptive view of the action of the stressors in plants, even across large fields, with the drawback of a poor accuracy. When looking at the spatial scale, the effect of stress may imply modifications from DNA level (nanometers) up to cell (micrometers), full plant (millimeters to meters), and entire field (kilometers). While quantitative techniques are sensitive to the smallest scales, only qualitative approaches can be used for the larger ones. Emerging technologies from nuclear and medical physics, such as computed tomography, magnetic resonance imaging and positron emission tomography, are expected to bridge the gap of quantitative non-disruptive morphologic and functional measurements at larger scale. In this review we analyze the landscape of the different technologies nowadays available, showing the benefits of each approach in plant stress detection, with a particular focus on the gaps, which will be filled in the nearby future by the emerging nuclear physics approaches to agriculture.
Inactivation of N-Acetylglucosaminyltransferase I and α1,3-Fucosyltransferase Genes in Nicotiana tabacum BY-2 Cells Results in Glycoproteins With Highly Homogeneous, High-Mannose N-Glycans
Authors: Herman Xavier , Far Johann , Courtoy Adeline , Bouhon Laurent , Quinton Loïc , De Pauw Edwin , Chaumont François , Navarre Catherine
Published: January 2021

Nicotiana tabacum Bright Yellow-2 (BY-2) suspension cells are among the most commonly used plant cell lines for producing biopharmaceutical glycoproteins. Recombinant glycoproteins are usually produced with a mix of high-mannose and complex N-glycans. However, N-glycan heterogeneity is a concern for the production of therapeutic or vaccine glycoproteins because it can alter protein activity and might lead to batch-to-batch variability. In this report, a BY-2 cell line producing glycoproteins devoid of complex N-glycans was obtained using CRISPR/Cas9 edition of two N-acetylglucosaminyltransferase I (GnTI) genes, whose activity is a prerequisite for the formation of all complex N-glycans. The suppression of complex N-glycans in the GnTI-knocked out (KO) cell lines was assessed by Western blotting. Lack of β1,2-xylose residues confirmed the abolition of GnTI activity. Unexpectedly, α1,3-fucose residues were still detected albeit dramatically reduced as compared with wild-type cells. To suppress the remaining α1,3-fucose residues, a second genome editing targeted both GnTI and α1,3-fucosyltransferase (FucT) genes. No β1,2-xylose nor α1,3-fucose residues were detected on the glycoproteins produced by the GnTI/FucT-KO cell lines. Absence of complex N-glycans on secreted glycoproteins of GnTI-KO and GnTI/FucT-KO cell lines was confirmed by mass spectrometry. Both cell lines produced high-mannose N-glycans, mainly Man5 (80 and 86%, respectively) and Man4 (16 and 11%, respectively). The high degree of N-glycan homogeneity and the high-mannose N-glycosylation profile of these BY-2 cell lines is an asset for their use as expression platforms.
Beyond Passion and Perseverance: Review and Future Research Initiatives on the Science of Grit
Authors: Datu Jesus Alfonso D.
Published: January 2021

Grit, which is originally conceptualized as passion and perseverance for long-term goals, has been associated with optimal performance. Although previous meta-analytic and systematic reviews summarized how grit relates to performance outcomes, they possess considerable shortcomings, such as (a) absence of summary on the association of grit with well-being outcomes; (b) absence of discussion on social, psychological, and emotional mechanisms linking grit to well-being; and (c) lack of elaboration on how alternative models can resolve fundamental problems in the grit construct. This integrative review provides a comprehensive summary on the link of grit to performance and well-being outcomes. Importantly, it elaborates how alternative models can potentially address flaws in the existing grit theory. Future research directions are discussed on how to move forward the science of grit.
Grace Under Pressure: Resilience, Burnout, and Wellbeing in Frontline Workers in the United Kingdom and Republic of Ireland During the SARS-CoV-2 Pandemic
Authors: Sumner Rachel C. , Kinsella Elaine L.
Published: January 2021

The coronavirus pandemic has necessitated extraordinary human resilience in order to preserve and prolong life and social order. Risks to health and even life are being confronted by workers in health and social care, as well as those in roles previously never defined as “frontline,” such as individuals working in community supply chain sectors. The strategy adopted by the United Kingdom (UK) government in facing the challenges of the pandemic was markedly different from other countries. The present study set out to examine what variables were associated with resilience, burnout, and wellbeing in all sectors of frontline workers, and whether or not these differed between the UK and Republic of Ireland (RoI). Individuals were eligible if they were a frontline worker (in health and social care, community supply chain, or other emergency services) in the UK or RoI during the pandemic. Part of a larger, longitudinal study, the participants completed an online survey to assess various aspects of their daily and working lives, along with their attitudes toward their government’s handling of the crisis, and measurement of psychological variables associated with heroism (altruism, meaning in life, and resilient coping). A total of 1,305 participants (N = 869, 66.6% from the UK) provided sufficient data for analysis. UK-based workers reported lower wellbeing than the RoI-based participants. In multivariate models, both psychological and pandemic-related variables were associated with levels of resilience, burnout, and wellbeing in these workers, but which pandemic-related variables were associated with outcomes differed depending on the country. The judgment of lower timeliness in their government’s response to the pandemic appeared to be a key driver of each outcome for the UK-based frontline workers. These findings provide initial evidence that the different strategies adopted by each country may be associated with the overall wellbeing of frontline workers, with higher detriment observed in the UK. The judgment of the relatively slow response of the UK government to instigate their pandemic measures appears to be associated with lower resilience, higher burnout, and lower wellbeing in frontline workers in the UK.
The Practice of Character Strengths: Unifying Definitions, Principles, and Exploration of What’s Soaring, Emerging, and Ripe With Potential in Science and in Practice
Authors: Niemiec Ryan M. , Pearce Ruth
Published: January 2021

What does it mean to be “strengths-based” or to be a “strengths-based practitioner?” These are diffuse areas that are generic and ill-defined. Part of the confusion arises from the customary default of practitioners and leaders across many cultures to label anything positive or complimentary as “strengths-based,” whether that be an approach, a theoretical orientation, an intervention, or a company. Additional muddle is created by many researchers and practitioners not making distinctions between very different categories of “strength” in human beings – strengths of character, of talent/ability, of interest/passion, of skill/competency, to name a few. To add clarity and unification across professions, we offer seven characteristics and a comprehensive definition for a character strengths-based practitioner. We center on the type of strength referred to as character strengths and explore six guiding principles for understanding character strengths (e.g., character is plural; character is being and doing) and their practical corollaries. Reflecting this foundation and based on character strengths research, our longstanding work with strengths, discussions with practitioners across the globe, and a practitioner survey asking about strength practices (N= 113), we point out several character strengths practices or approaches we describe as soaring (e.g., explore and encourage signature strengths; practice strengths-spotting), emerging (e.g., the integration of mindfulness and character strengths), or ripe with potential (e.g., phasic strengths; the tempering effect; the towing effect). We use the same framework for describing general research domains. Some areas of research in character strengths are soaring with more than 25 studies (e.g., workplace/organizations), some are emerging with a handful of studies (e.g., health/medicine), and others are ripe with potential that have none or few studies yet opportunity looms large for integrating character science (e.g., peace/conflict studies). Using this framework, we seek to advance the exchange and collaboration between researcher and practitioner, as well as to advance the science and practice of character strengths.
State-Anxiety and Academic Burnout Regarding University Access Selective Examinations in Spain During and After the COVID-19 Lockdown
Authors: Fernández-Castillo Antonio
Published: January 2021

Coping with assessment tests are known to generate anxiety frequently in the students who face them. In academic circumstances with the continued presence of emotional disturbance, high demand, and stress, emotional and physical fatigue, typical of burnout syndrome, and can be detected. Anxiety and burnout are related to each other and even more closely in high-stakes tests. One of these tests is the examination imposed in Spain for access to the university. The objective of this work is to analyze the presence of anxiety and burnout and the relationship between them in students who face these tests, both during the confinement situation due to the COVID-19 pandemic and during the pandemic after the lockdown. For this purpose, we used a sample of 1,021 students with a mean age of 17.89 (SD = 1.22, range 17–27). Of these, 866 (84.8%) were students who were taking the test, while the rest were university students who had passed it recently. Our results show high levels of anxiety and burnout in students who face the evaluation test during the COVID-19 pandemic, sustained over time and especially in comparison with students who had already taken the exam. The association between higher levels of anxiety and higher levels of burnout in the students who take these exams was also verified. These results link the relationship between these two variables more solidly and suggest the need to include address anxiety to reduce burnout levels in these students. The results are discussed with regard to prior evidence and their applications.
The Locus Coeruleus- Norepinephrine System in Stress and Arousal: Unraveling Historical, Current, and Future Perspectives
Authors: Ross Jennifer A. , Van Bockstaele Elisabeth J.
Published: January 2021

Arousal may be understood on a spectrum, with excessive sleepiness, cognitive dysfunction, and inattention on one side, a wakeful state in the middle, and hypervigilance, panic, and psychosis on the other side. However, historically, the concepts of arousal and stress have been challenging to define as measurable experimental variables. Divergent efforts to study these subjects have given rise to several disciplines, including neurobiology, neuroendocrinology, and cognitive neuroscience. We discuss technological advancements that chronologically led to our current understanding of the arousal system, focusing on the multifaceted nucleus locus coeruleus. We share our contemporary perspective and the hypotheses of others in the context of our current technological capabilities and future developments that will be required to move forward in this area of research.
Social Distancing: Prevalence of Depressive, Anxiety, and Stress Symptoms Among Brazilian Students During the COVID-19 Pandemic
Authors: Esteves Cristiane Silva , Oliveira Camila Rosa de , Argimon Irani Iracema de Lima
Published: January 2021

Social distancing due to the COVID-19 pandemic can impact mental health, triggering symptoms such as anxiety, stress and depression. Therefore, this study aimed to assess the levels of anxiety, depression and stress during the period of social distancing due to COVID-19 in students from a campus of the Federal Institute in the metropolitan area of Porto Alegre/RS. A correlational and exploratory study was performed. The sample of the present research was composed by 208 students, who responded to a self-administered online questionnaire with sociodemographic variables and the Depression, Anxiety and Stress Scale Short Form – DASS-21. The detected prevalence of symptoms classified as moderate-severe was 49% for stress, 39% for depression and 33% for anxiety. An association was found between higher levels of anxiety symptoms (OR = 5.652; 95% CI = 2.872–11.123; p < 0.001), depression (OR = 3.289; 95% CI = 1.810–5.978; p < 0.001) and stress (OR = 5.684; 95% CI = 3.120–10.355; p < 0.001) with occurrence of sleep problems during the period of social distancing. There was a protective factor provided by regular physical exercise in relation to depressive symptoms (OR = 0.490; 95% CI = 0.250–0.960; p =0.033). These data are extremely important for understanding the adverse effect on the mental health of students and for developing psychological support strategies, thus promoting well-being during and after the pandemic.