bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lutein and Zeaxanthin in the Lipid Bilayer–Similarities and Differences Revealed by Computational Studies
Authors: Makuch Krzysztof , Hryc Jakub , Markiewicz Michal , Pasenkiewicz-Gierula Marta 
Published: October 2021

Lutein and zeaxanthin are two similar carotenoids of the xanthophyll subgroup. Carotenoids are synthesized almost entirely by plants but are also present in significant amounts in animals. They are essential components of the lipid matrix of biomembranes, and one of their functions is to protect cells from light radiation, free radicals and oxidative stress. Carotenoids, depending on their chemical structure, can locate at various positions and in different orientations in the bilayer. Xanthophylls (XAN) are polar and in the bilayer are positionally restricted. In the case of lutein and zeaxanthin, whose both ionone rings are hydroxy-substituted and as such are anchored in the lipid bilayer interfaces, the position is generally transmembrane. However, both experimental and computer modelling studies indicate that lutein can also locate horizontally below the bilayer interface. This location has never been observed for zeaxanthin. To find a molecular-level explanation for the difference in the orientations of the XAN molecules in the bilayer, a number of phosphatidylcholine-XAN bilayers were constructed and molecular dynamics (MD) simulated for 1.1 µs each. The all-trans XAN molecules were initially placed either parallel or perpendicular to the bilayer surface. With the exception of one lutein, the horizontally placed molecules adopted the transmembrane orientation within 100–600 ns. On the basis of detailed analyses of the XAN orientations and the numbers and lifetimes of their interactions in the bilayer, a plausible explanation is offered as to why a lutein molecule may remain in the horizontal orientation while zeaxanthin does not. Contrary to common believe, lutein horizontal orientation is not related to the ε-ring rotation around the C6′-C7′ bond.
Deep-Learning Radiomics for Discrimination Conversion of Alzheimer's Disease in Patients With Mild Cognitive Impairment: A Study Based on 18F-FDG PET Imaging
Authors: Zhou Ping , Zeng Rong , Yu Lun , Feng Yabo , Chen Chuxin , Li Fang , Liu Yang , Huang Yanhui , Huang Zhongxiong ,   the Alzheimer's Disease Neuroimaging Initiative
Published: October 2021

Objectives: Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder and the most common form of dementia in the older people. Some types of mild cognitive impairment (MCI) are the clinical precursors of AD, while other MCI forms tend to remain stable over time and do not progress to AD. To discriminate MCI patients at risk of AD from stable MCI, we propose a novel deep-learning radiomics (DLR) model based on 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) images and combine DLR features with clinical parameters (DLR+C) to improve diagnostic performance.Methods:18F-fluorodeoxyglucose positron emission tomography (PET) data from the Alzheimer's disease Neuroimaging Initiative database (ADNI) were collected, including 168 patients with MCI who converted to AD within 3 years and 187 patients with MCI without conversion within 3 years. These subjects were randomly partitioned into 90 % for the training/validation group and 10 % for the independent test group. The proposed DLR approach consists of three steps: base DL model pre-training, network features extraction, and integration of DLR+C, where a convolution network serves as a feature encoder, and a support vector machine (SVM) operated as the classifier. In comparative experiments, we compared our DLR+C method with four other methods: the standard uptake value ratio (SUVR) method, Radiomics-ROI method, Clinical method, and SUVR + Clinical method. To guarantee the robustness, 10-fold cross-validation was processed 100 times.Results: Under the DLR model, our proposed DLR+C was advantageous and yielded the best classification performance in the diagnosis of conversion with the accuracy, sensitivity, and specificity of 90.62 ± 1.16, 87.50 ± 0.00, and 93.39 ± 2.19%, respectively. In contrast, the respective accuracy of the other four methods reached 68.38 ± 1.27, 73.31 ± 6.93, 81.09 ± 1.97, and 85.35 ± 0.72 %. These results suggested the DLR approach could be used successfully in the prediction of conversion to AD, and that our proposed DLR-combined clinical information was effective.Conclusions: This study showed DLR+C could provide a novel and valuable method for the computer-assisted diagnosis of conversion to AD from MCI. This DLR+C method provided a quantitative biomarker which could predict conversion to AD in MCI patients.
Clinical, Neurophysiological, and MRI Markers of Fampridine Responsiveness in Multiple Sclerosis—An Explorative Study
Authors: Mamoei Sepehr , Jensen Henrik Boye , Pedersen Andreas Kristian , Nygaard Mikkel Karl Emil , Eskildsen Simon Fristed , Dalgas Ulrik , Stenager Egon 
Published: October 2021

Objective: Persons with multiple sclerosis (PwMS), already established as responders or non-responders to Fampridine treatment, were compared in terms of disability measures, physical and cognitive performance tests, neurophysiology, and magnetic resonance imaging (MRI) outcomes in a 1-year explorative longitudinal study.Materials and Methods: Data from a 1-year longitudinal study were analyzed. Examinations consisted of the timed 25-foot walk test (T25FW), six spot step test (SSST), nine-hole peg test (9-HPT), five times sit-to-stand test (5-STS), symbol digit modalities test (SDMT), transcranial magnetic stimulation (TMS) elicited motor evoked potentials (MEP) examining central motor conduction times (CMCT), peripheral motor conduction times (PMCT) and their amplitudes, electroneuronography (ENG) of the lower extremities, and brain structural MRI measures.Results: Forty-one responders and eight non-responders to Fampridine treatment were examined. There were no intergroup differences except for the PMCT, where non-responders had prolonged conduction times compared to responders to Fampridine. Six spot step test was associated with CMCT throughout the study. After 1 year, CMCT was further prolonged and cortical MEP amplitudes decreased in both groups, while PMCT and ENG did not change. Throughout the study, CMCT was associated with the expanded disability status scale (EDSS) and 12-item multiple sclerosis walking scale (MSWS-12), while SDMT was associated with number of T2-weighted lesions, lesion load, and lesion load normalized to brain volume.Conclusions: Peripheral motor conduction time is prolonged in non-responders to Fampridine when compared to responders. Transcranial magnetic stimulation-elicited MEPs and SDMT can be used as markers of disability progression and lesion activity visualized by MRI, respectively.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT03401307.
Effects of Repetitive Transcranial Magnetic Stimulation in Patients With Mild Cognitive Impairment: A Meta-Analysis of Randomized Controlled Trials
Authors: Zhang Xinqi , Lan Xiaoyong , Chen Chanjuan , Ren Huixia , Guo Yi 
Published: October 2021

Background: Mild cognitive impairment (MCI) is an intermediary state between normal aging and dementia. It has a high risk of progression in patients with Alzheimer's disease (AD). Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique used to improve cognitive deficits in patients with MCI and AD. Although previous meta-analyses included studies carried on patients with MCI and AD, few studies have analyzed patients with MCI independently. This meta-analysis aimed to evaluate the effects and safety of rTMS on cognition function in patients with MCI and factors that may influence such effects.Methods: Data used in this study were searched and screened from different databases, including PubMed, Web of Science, Embase, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Chinese Technical Periodicals (VIP), Wanfang Database, and China BioMedical Literature Database (SinoMed). The retrieved studies were carefully reviewed, data were extracted, and the quality of data was assessed.Results: A total of 12 studies involving 329 patients with MCI were included in the present meta-analysis. The analyses results revealed that rTMS improved cognitive function [standardized mean difference (SMD) = 0.83, 95% confidence interval (CI) = 0.44–1.22, p = 0.0009] and memory function (SMD = 0.73, 95% CI = 0.48–0.97, p &lt; 0.00001) in the MCI + rTMS active group when compared to the sham stimulation group. The showed that: (1) cognitive improvement was more pronounced under high-frequency rTMS stimulation of multiple sites, such as the bilateral dorsolateral prefrontal cortex and (2) more than 10 rTMS stimulation sessions produced higher improvement on cognition function in patients with MCI.Conclusions: This study shows that rTMS can improve cognitive function in patients with MCI, especially when applied at high frequency, multi-site, and for a prolonged period. However, further studies are required to validate these findings and explore more effective stimulation protocols and targets.Systematic Review Registration: [http://www.crd.york.ac.uk/PROSPERO/], identifier: CRD 42021238708.
Impact of the COVID-19 Pandemic on Stress, Sleep, and Oral Health in University Students
Authors: Cerqueira Thaissa Reis do Carmo , Batista Sayene Garcia , de Mello Elson Braga , DosSantos Marcos Fabio , Tuñas Inger Teixeira de Campos 
Published: October 2021

Background:The COVID-19 pandemic, a disease caused by Sars-CoV-2, has become a worldwide stressor, especially as it represents a new viral infection, which spreads quickly and easily, without prior knowledge about vaccination, and absence, to this moment, of a medication that is totally effective against the disease.Objective:The aim of this observational study was to provide a general evaluation, through a questionnaire applied to students in the health field of the Federal University of Rio de Janeiro, on the psychological impacts and behavioral changes generated by the COVID-19 pandemic on oral health, especially the triggering or exacerbation of bruxism and temporomandibular disorders (TMD).Methods:In order to verify the impacts of the pandemic on the health of UFRJ healthcare students, a non-randomized survey was performed with 370 students.Results:It was found that 72% of the students had their sleep routine altered, 65% had greater difficulty in keeping their spirits up, there was a statistically significant increase in emotional stress, headaches, and daytime teeth clenching.Conclusion:It was possible to conclude that the outbreak of COVID-19 resulted in psychological, physiological and behavioral impacts on students.
Discovery of a Series of Theophylline Derivatives Containing 1,2,3-Triazole for Treatment of Non-Small Cell Lung Cancer
Authors: Ye Jiahui , Mao Longfei , Xie Luoyijun , Zhang Rongjun , Liu Yulin , Peng Lizeng , Yang Jianxue , Li Qingjiao , Yuan Miaomiao 
Published: October 2021

Chemotherapy is the most common clinical treatment for non-small cell lung cancer (NSCLC), but low efficiency and high toxicity of current chemotherapy drugs limit their clinical application. Therefore, it is urgent to develop hypotoxic and efficient chemotherapy drugs. Theophylline, a natural compound, is safe and easy to get, and it can be used as a modified scaffold structure and hold huge potential for developing safe and efficient antitumor drugs. Herein, we linked theophylline with different azide compounds to synthesize a new type of 1,2,3-triazole ring-containing theophylline derivatives. We found that some theophylline1,2,3-triazole compounds showed a good tumor-suppressive efficacy. Especially, derivative d17 showed strong antiproliferative activity against a variety of cancer cells in vitro, including H460, A549, A2780, LOVO, MB-231, MCF-7, OVCAR3, SW480, and PC-9. It is worth noting that the two NSCLC cell lines H460 H and A549 are sensitive to compound d17 particularly, with IC50 of 5.929 ± 0.97 μM and 6.76 ± 0.25 μM, respectively. Compound d17 can significantly induce cell apoptosis by increasing the ratio of apoptotic protein Bax/Bcl-2 by downregulating the expression of phosphorylated Akt protein, and it has little toxicity to normal hepatocyte cells LO2 at therapeutic concentrations. These data indicate that these theophylline acetic acid-1,2,3-triazole derivatives may be potential drug candidates for anti-NSCLC and are worthy of further study.
Magnolol Attenuates Right Ventricular Hypertrophy and Fibrosis in Hypoxia-Induced Pulmonary Arterial Hypertensive Rats Through Inhibition of the JAK2/STAT3 Signaling Pathway
Authors: Fu Minyi , Luo Fangmei , Wang Eli , Jiang Yueping , Liu Shao , Peng Jun , Liu Bin 
Published: October 2021

Right ventricular (RV) remodeling is one of the essential pathological features in pulmonary arterial hypertension (PAH). RV hypertrophy or fibrosis are the leading causes of RV remodeling. Magnolol (6, 6′, 7, 12-tetramethoxy-2,2′-dimethyl-1-β-berbaman, C18H18O2) is a compound isolated from Magnolia Officinalis. It possesses multiple pharmacological activities, such as anti-oxidation and anti-inflammation. This study aims to evaluate the effects and underlying mechanisms of magnolol on RV remodeling in hypoxia-induced PAH. In vivo, male Sprague Dawley rats were exposed to 10% O2 for 4 weeks to establish an RV remodeling model, which showed hypertrophic and fibrotic features (increases of Fulton index, cellular size, hypertrophic and fibrotic marker expression), accompanied by an elevation in phosphorylation levels of JAK2 and STAT3; these changes were attenuated by treating with magnolol. In vitro, the cultured H9c2 cells or cardiac fibroblasts were exposed to 3% O2 for 48 h to induce hypertrophy or fibrosis, which showed hypertrophic (increases in cellular size as well as the expression of ANP and BNP) or fibrotic features (increases in the expression of collagen Ⅰ, collagen Ⅲ, and α-SMA). Administration of magnolol and TG-101348 or JSI-124 (both JAK2 selective inhibitors) could prevent myocardial hypertrophy and fibrosis, accompanied by the decrease in the phosphorylation level of JAK2 and STAT3. Based on these observations, we conclude that magnolol can attenuate RV hypertrophy and fibrosis in hypoxia-induced PAH rats through a mechanism involving inhibition of the JAK2/STAT3 signaling pathway. Magnolol may possess the potential clinical value for PAH therapy.
Risk for Cardiovascular Disease and One-Year Mortality in Patients With Chronic Obstructive Pulmonary Disease and Obstructive Sleep Apnea Syndrome Overlap Syndrome
Authors: Tang Manyun , Wang Yidan , Wang Mengjie , Tong Rui , Shi Tao 
Published: October 2021

Background: Patients with chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSAS) overlap syndrome (OS) are thought to be at increased risk for cardiovascular diseases.Objective: To evaluate the burden of cardiovascular diseases and long-term outcomes in patients with OS.Methods: This was a retrospective cohort study. The prevalence of cardiovascular diseases and 1-year mortality were compared among patients diagnosed with OS (OS group), COPD alone (COPD group) and OSAS alone (OSAS group), and Cox proportional hazards models were used to assess independent risk factors for all-cause mortality.Results: Overall, patients with OS were at higher risk for pulmonary hypertension (PH), heart failure and all-cause mortality than patients with COPD or OSAS (all p &lt; 0.05). In multivariate Cox regression analysis, the Charlson comorbidity index (CCI) score [adjusted hazard ratio (aHR): 1.273 (1.050–1.543); p = 0.014], hypertension [aHR: 2.006 (1.005–4.004); p = 0.048], pulmonary thromboembolism (PTE) [aHR: 4.774 (1.335–17.079); p = 0.016] and heart failure [aHR: 3.067 (1.521–6.185); p = 0.002] were found to be independent risk factors for 1-year all-cause mortality.Conclusion: Patients with OS had an increased risk for cardiovascular diseases and 1-year mortality. More efforts are needed to identify the causal relationship between OS and cardiovascular diseases, promoting risk stratification and the management of these patients.
Cystic Fibrosis Transmembrane Conductance Regulator Folding Mutations Reveal Differences in Corrector Efficacy Linked to Increases in Immature Cystic Fibrosis Transmembrane Conductance Regulator Expression
Authors: Peters Kathryn W. , Gong Xiaoyan , Frizzell Raymond A. 
Published: October 2021

Background: Most cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that lead to protein misfolding and degradation by the ubiquitin–proteasome system. Previous studies demonstrated that PIAS4 facilitates the modification of wild-type (WT) and F508del CFTR by small ubiquitin-like modifier (SUMO)-1, enhancing CFTR biogenesis by slowing immature CFTR degradation and producing increased immature CFTR band B.Methods: We evaluated two correction strategies using misfolding mutants, including the common variant, F508del. We examined the effects on mutant expression of co-expression with PIAS4 (E3 SUMO ligase), and/or the corrector, C18. To study the impact of these correction conditions, we transfected CFBE410- cells, a bronchial epithelial cell line, with a CFTR mutant plus: (1) empty vector, (2) empty vector plus overnight 5 μM C18, (3) PIAS4, and (4) PIAS4 plus C18. We assessed expression at steady state by immunoblot of CFTR band B, and if present, band C, and the corresponding C:B band ratio. The large PIAS4-induced increase in band B expression allowed us to ask whether C18 could act on the now abundant immature protein to enhance correction above the control level, as reported by the C:B ratio.Results: The data fell into three mutant CFTR categories as follows: (1) intransigent: no observable band C under any condition (i.e., C:B = 0); (2) throughput responsive: a C:B ratio less than control, but suggesting that the increased band C resulted from PIAS4-induced increases in band B production; and (3) folding responsive: a C:B ratio greater than control, reflecting C18-induced folding greater than that expected from increased throughput due to the PIAS4-induced band B level.Conclusion: These results suggest that the immature forms of CFTR folding intermediates occupy different loci within the energetic/kinetic folding landscape of CFTR. The evaluation of their properties could assist in the development of correctors that can target the more difficult-to-fold mutant conformations that occupy different sites within the CFTR folding pathway.
Prefrontal Cortex Oxygenation During Endurance Performance: A Systematic Review of Functional Near-Infrared Spectroscopy Studies
Authors: De Wachter Jonas , Proost Matthias , Habay Jelle , Verstraelen Matthias , Díaz-García Jesús , Hurst Philip , Meeusen Romain , Van Cutsem Jeroen , Roelands Bart 
Published: October 2021

Introduction: A myriad of factors underlie pacing-/exhaustion-decisions that are made during whole-body endurance performance. The prefrontal cortex (PFC) is a brain region that is crucial for decision-making, planning, and attention. PFC oxygenation seems to be a mediating factor of performance decisions during endurance performance. Nowadays, there is no general overview summarizing the current knowledge on how PFC oxygenation evolves during whole-body endurance performance and whether this is a determining factor.Methods: Three electronic databases were searched for studies related to the assessment of PFC oxygenation, through near-IR spectroscopy (NIRS), during endurance exercise. To express PFC oxygenation, oxygenated (HbO2) and deoxygenated hemoglobin (HHb) concentrations were the primary outcome measures.Results: Twenty-eight articles were included. Ten articles focused on assessing prefrontal oxygenation through a maximal incremental test (MIT) and 18 focused on using endurance tasks at workloads ranging from low intensity to supramaximal intensity. In four MIT studies measuring HbO2, an increase of HbO2 was noticed at the respiratory compensation point (RCP), after which it decreased. HbO2 reached a steady state in the four studies and increased in one study until exhaustion. All studies found a decrease or steady state in HHb from the start until RCP and an increase to exhaustion. In regard to (non-incremental) endurance tasks, a general increase in PFC oxygenation was found while achieving a steady state at vigorous intensities. PCF deoxygenation was evident for near-to-maximal intensities at which an increase in oxygenation and the maintenance of a steady state could not be retained.Discussion/Conclusion: MIT studies show the presence of a cerebral oxygenation threshold (ThCox) at RCP. PFC oxygenation increases until the RCP threshold, thereafter, a steady state is reached and HbO2 declines. This study shows that the results obtained from MIT are transferable to non-incremental endurance exercise. HbO2 increases during low-intensity and moderate-intensity until vigorous-intensity exercise, and it reaches a steady state in vigorous-intensity exercise. Furthermore, ThCox can be found between vigorous and near-maximal intensities. During endurance exercise at near-maximal intensities, PFC oxygenation increases until the value exceeding this threshold, resulting in a decrease in PFC oxygenation. Future research should aim at maintaining and improving PFC oxygenation to help in improving endurance performance and to examine whether PFC oxygenation has a role in other performance-limiting factors.
Effectiveness of Physical Activity Intervention on ADHD Symptoms: A Systematic Review and Meta-Analysis
Authors: Xie Yongtao , Gao Xuping , Song Yiling , Zhu Xiaotong , Chen Mengge , Yang Li , Ren Yuanchun 
Published: October 2021

Objective: To assess the effectiveness of physical activity (PA) intervention on attention-deficit/hyperactivity disorder (ADHD)-related symptoms.Method: Studies that investigated PA intervention for ADHD-related symptoms were identified through searching PubMed, Web of Science, Cochrane Library, and Embase databases from inception through June 2021. Standardized mean difference (SMD) with 95% confidence interval (CI) was used to assess the effectiveness of PA intervention on improving ADHD-related symptoms. The meta-analyses were conducted using fixed-effect or random-effect models according to the heterogeneity of the studies.Results: Nine before–after studies (232 participants) and 14 two-group control studies (162 participants/141 controls) were included in this meta-analysis. Combined results for before–after studies indicated significant improvements on all studied ADHD-related symptoms (inattention: SMD = 0.604, 95% CI: 0.374–0.834, p &lt; 0.001; hyperactivity/impulsivity: SMD = 0.676, 95% CI: 0.401–0.950, p &lt; 0.001; emotional problems: SMD = 0.416, 95% CI: 0.283–0.549, p &lt; 0.001; behavioral problems: SMD = 0.347, 95% CI: 0.202–0.492, p &lt; 0.001). Meta-analyses for two-group control studies further confirmed that PA intervention significantly improved the inattentive symptom (SMD = 0.715, 95% CI: 0.105, 1.325, p = 0.022). Subgroup analyses suggested significant beneficial effect on inattention symptoms in children. Moreover, closed motor skills were beneficial for hyperactive/impulsive problems (SMD = 0.671, p &lt; 0.001), while open motor skills were beneficial for attention problems (SMD = 0.455, p = 0.049). When excluding studies with combined medication, the studies in unmedicated participants in before–after studies still showed significant results in all studied ADHD-related symptoms as in the overall analysis. Given the limited sample size, the best frequency and intensity of PA intervention need further investigation.Conclusion: Our results suggested that PA intervention could possibly improve ADHD-related symptoms, especially inattention symptoms. Closed-skill and open-skill activities could be beneficial for hyperactivity/impulsivity and inattention symptoms, respectively. Further high-quality randomized clinical trials with large sample size are needed.