bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Network-Based Approach to Investigate the Neuroprotective Effects and Mechanisms of Action of Huangqi-Chuanxiong and Sanleng-Ezhu Herb Pairs in the Treatment of Cerebral Ischemic Stroke
Authors: Zhao Lin , Ding Li Dong , Xia Zi Hao , Sheng Peng , Shen Meng Meng , Cai Zhong Ming , Yan Bing Chun 
Published: March 2022

Objective: We aimed to investigate the effect and mechanisms of action of two drug pairs [Huangqi-Chuanxiong and Sanleng-Ezhu Herb (HCSE)] on the treatment of ischemic stroke.Materials and methods: We mined the current literature related to ischemic stroke and formulated a new formulation of Chinese herbs. Then, we identified the main candidate target genes of the new formulation by network pharmacology. Next, we performed enrichment analysis of the target genes to identify the potential mechanism of action of the new formulation in the treatment of ischemic stroke. Next, we experimentally validated the mechanism of action of the new formulation against ischemic stroke. Infarct volume and neurological deficits were evaluated by 2,3,5-triphenyltetrazolium (TTC) staining and Longa’s score, respectively. The predicted pathways of signal-related proteins were detected by western blotting.Results: We mined the current literature and identified a new formulation of Chinese herbs for the treatment of ischemic stroke. The formulation included Huangqi, Chuanxiong, Sanleng and Ezhu. Next, we used network pharmacological analysis to identify 23 active compounds and 327 target genes for the new formulation. The key target genes were MAPK3, MAPK1, HSP90AA1, STAT3, PIK3R1, PIK3CA and AKT1. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed significant enrichment of the PI3K/AKT and MAPK/ERK signaling pathways. By performing experiments, we found that the new formulation reduced the infarct volume of middle cerebral artery occlusion (MCAO) induced mice and activated the PI3K/AKT and MAPK/ERK signaling pathways. These findings confirmed that the new formulation has a significant protective effect against ischemic stroke injury by activating the PI3K/AKT and MAPK/ERK signaling pathways.Conclusion: We identified a new treatment formulation for ischemic stroke by data mining and network pharmacological target prediction. The beneficial effects of the new formulation act by regulating multiple target genes and pathways. The mechanism of action of the new formulation may be related to the AKT and ERK signaling pathways. Our findings provide a theoretical basis for the effects of the new formulation on ischemic stroke injury.
Exploring the Potential Toxicological Mechanisms of Vine Tea on the Liver Based on Network Toxicology and Transcriptomics
Authors: Xiao Fangyu , Qiu Jihua , Zhao Ying 
Published: March 2022

Objective: This study focuses on whether vine tea contains potentially toxic components that trigger hepatotoxicity as a mechanism of action, which further provides some reference for the consumption and guides future product development of vine tea.Methods: The chemical components of vine tea were collected from the reported literature and the toxicological information matched with the CTD database was collected, and the dataset of potential toxic components was established. The toxic components were submitted to the PharmMapper server to obtain potential targets. At the same time, the relevant targets were searched in the CTD database and GeneCards database with keywords such as “Hepatic Toxicity,” “Liver Damage,” and “Drug-induced liver injury.” After intersection, the potential hepatotoxic targets of vine tea were obtained. The protein interactions of potential hepatotoxic targets of vine tea were analyzed by the STRING database. Protein–protein interaction (PPI) networks were constructed by Cytoscape3.6.1 software. The GO molecular function and KEGG pathway of hepatotoxic targets were enriched by the R package to screen the key targets. The role of the components and key targets was analyzed by the LEDOCK program. The data from GEO database were mined for the functional correlation characterized by cell transcriptional expression caused by vine tea as a disturbance factor.Results: This study has searched 34 potential toxic components and 57 potential hepatotoxic targets of vine tea, and the result showed that these targets were mainly involved in oxidative stress, cell metabolism, and apoptosis to affect the liver.Conclusion: Vine tea has the interrelationship of multi-components, multi-targets, and multi-pathways. At the cellular level, the toxic components of vine tea, mainly flavonoids, may promote oxidative stress, promote oxidation to produce free radicals, guide apoptosis, and affect cell metabolism and other cytotoxic mechanisms. However, this hepatotoxicity is related to the dose, duration of vine tea, and individual differences. This study revealed the potential hepatotoxic components of vine tea and provides a reference for further research and development of related functional products.
Survival Prediction of Patients Treated With Immune Checkpoint Inhibitors via KRAS/TP53/EGFR-Single Gene Mutation
Authors: Liu Shui , Geng Shuai , Shi Ning , Zhang Lili , Xue Wenxin , Li Yiwen , Jiang Kai 
Published: March 2022

Background: Immune checkpoint inhibitors (ICIs) have become an effective treatment option for cancer. KRAS, EGFR and TP53 are common mutated oncogenes in cancer whose single gene status may predict the therapeutic effect of clinical ICIs. In this efficacy evaluation, we aimed to clarify whether the single gene mutation status of KRAS, EGFR or TP53 affects the survival benefits of ICIs in cancer patients.Methods: We used PubMed, Cochrane Library, web of science, and clinical trials Gov database to retrieve qualified documents, the time was up to January 2022. Hazard ratios (HRS) and 95% confidence intervals (CIs) were used to determine the single gene mutation status and no progression of KRAS, EGFR or TP53.Results: A total of 19 studies included 7029 cancer patients treated with ICIs. The results showed that KRAS, EGFR or TP53 single gene mutation could significantly improve PFS and OS in patients receiving ICIs, but the degree of improvement was different. The risk of prolongation of PFS (HR = 1.48, 95% CI = 1.19-1.85, p = 0.0004) and OS (HR = 1.68, 95% CI = 1.36-2.07, p &lt; 0.00001) caused by TP53 single gene mutation was relatively high, the risk ratio of prolongation of PFS (HR = 1.38, 95% CI = 1.21-1.57, p &lt; 0.00001) and OS (HR = 1.56, 95% CI = 1.20-2.04, p = 0.001) caused by EGFR single gene mutation was the second, the risk ratio of prolongation of PFS (HR = 1.33, 95% CI = 1.12-1.57, p = 0.001) and OS (HR = 1.39, 95% CI = 1.18-1.63, p &lt; 0.00001) caused by KRAS single gene mutation was relatively low, and the results were significantly different.Conclusion: In cancer patients, KRAS, EGFR or TP53 single gene status is correlated with the benefits of immunotherapy PFS and OS, which suggests that gene sequencing should be carried out in time in the process of clinical treatment to determine the gene mutation of patients and better predict the clinical treatment effect of ICIs.
Dispositional Mindfulness and Post-traumatic Stress Symptoms in Emergency Nurses: Multiple Mediating Roles of Coping Styles and Emotional Exhaustion
Authors: Yuan Yuan , Wang Zonghua , Shao Yanxia , Xu Xia , Lu Fang , Xie Fei , Sun Wei 
Published: March 2022

ObjectiveTo explore the relationships between dispositional mindfulness (DM) and their post-traumatic stress symptoms (PTSS) of emergency nurses, and the mediating effects of coping styles and emotional exhaustion (EE).MethodsA cross-sectional survey study was conducted to collect data on DM, coping styles, EE, and PTSS among 571 emergency nurses from 20 hospitals in Chongqing, China. Correlation and structural equation models (SEMs) were used to evaluate the relationship among variables.ResultsEmergency nurses with lower dispositional mindfulness, higher emotional exhaustion and preference for negative coping (NC) revealed more PTSS. The effect of NC on PTSS was partially mediated by emotional exhaustion. Negative coping and emotional exhaustion played concurrent and sequential mediating roles between dispositional mindfulness and PTSS.ConclusionThis study has made a significant contribution to existing literature. It was suggested to develop interventions aimed at enhancing mindfulness, reducing negative coping strategies, and alleviating emotional exhaustion, which may be effective at reducing or alleviating post-traumatic stress symptoms of emergency nurses.
Affective Valence and Enjoyment in High- and Moderate-High Intensity Interval Exercise. The Tromsø Exercise Enjoyment Study
Authors: Hammer Tord Markussen , Pedersen Sigurd , Pettersen Svein Arne , Rognmo Kamilla , Sagelv Edvard H. 
Published: March 2022

IntroductionExercise at high intensity may cause lower affective responses toward exercise compared with moderate intensity exercise. We aimed to elucidate affective valence and enjoyment in high- and moderate-high interval exercise.MethodsTwenty recreationally active participants (9 females, 11 males, age range: 20–51 years) underwent three different treadmill running exercise sessions per week over a 3-week period, in randomized order; (1) CE70: 45 min continuous exercise at 70% of heart rate maximum (HRmax), (2) INT80: 4 × 4 min intervals at 80% of HRmax, (3) INT90: 4 × 4 min intervals at 90% of HRmax. Pre-tests included graded submaximal steady state intensities and a test to exhaustion for determining peak oxygen uptake and HRmax. Affective valence (pleasure/displeasure) was measured before, during and after the sessions using the Feeling Scale (FS). Enjoyment was assessed before and after the sessions applying the Physical Activity Enjoyment Scale (PACES) and during the sessions using the Exercise Enjoyment Scale (EES).ResultsThe participants felt lower pleasure (between-sessions effect:p= 0.02,pη2: 0.13) during INT90 sessions (FS: 1.08, 95% CI: 0.35–1.92) compared with INT80 (FS: 2.35, 95% CI: 1.62–3.08,p= 0.052) and CE70 sessions (FS: 2.45, 95% CI: 1.72–3.18,p= 0.03), with no differences between INT80 and CE70 sessions (p= 1.00). There were higher enjoyment after INT80 sessions (PACES: 101.5, 95% CI: 95.7–107.3) versus CE70 sessions (PACES: 91.3 95% CI: 85.5–97.1,p= 0.046), and no differences between INT90 (PACES: 98.2, 95% CI: 92.4–103.4) and CE70 (p= 0.29) or INT80 (p= 1.00). For enjoyment during exercise, CE70 were perceived more enjoyable, and INT80 and INT90 less enjoyable in week 2 (EES: week x session:p= 0.01,pη2: 0.11; CE70: 4.3, 95% CI: 3.6–4.9, INT80: 4.6, 95% CI: 3.9–5.2, INT90: 4.0, 95% CI: 3.4–4.7) and 3 (EES: CE70: 4.2, 95% CI: 3.7–4.8, INT80: 4.8, 95% CI: 4.2–5.3, INT90: 4.3, 95% CI: 3.8–4.9) than in week 1 (EES: CE70: 3.5, 95% CI: 3.0–4.0, INT80: 5.0, 95% CI: 4.5–5.5, INT90: 4.5, 95% CI: 4.0–5.0).ConclusionThe negative affective consequences associated with high intensity interval exercise can be alleviated by keeping the intensity at or around 80% of HRmaxwhile preserving the beneficial enjoyment responses associated with interval exercise.
Empirical Study on the Relationship Between Vacation Schedule and Seafarers’ Fatigue in Chinese Seafarer Population
Authors: An Ji , Gao Wenting , Liu Runze , Liu Ziqi 
Published: March 2022

BackgroundFatigue is an important factor for the safety of ships. In order to alleviate fatigue of the seafarers, the STCW Convention (International Convention on Standards of Training, Certification, and Watchkeeping for Seafarers) has made many regulations on the working time of seafarers. At present, if a crew member takes only one day off at home before returning to work on the ship, the working time on the ship must be re-calculated again. If the time spent at home is not sufficient to allow the crew to recover, the regulations of only stipulating the working time, not stipulating the home vacation time, cannot guarantee the crew’s fatigue been well controlled. The aim of present study is to explore the relationship between vacation schedule and fatigue of the seafarers.MethodsIn present study, a simplified stress scale developed by the Ministry of Labor of Japan has been used as a measurement tool. The method of stratified sampling was adopted. Data collection mainly came from domestic ocean-going seafarers (n = 165). Analysis was conducted using the Cross (chi-square) analysis and hierarchical multiple regression analysis methods.ResultsWe found that there was no difference between crew members of different positions in terms of average vacation time and on-board service time (p &gt; 0.05). The length of last vacation time and this service time for seafarers of different positions showed obvious differences (p &lt; 0.01). The rank has a significant effect on the length of the last vacation (χ2 = 101.560, p = 0.000 &lt; 0.01) and the length of this service time (χ2 = 75.624, p = 0.000 &lt; 0.01). Also, the results showed that there was a significant negative correlation between the duration of vacation and overall fatigue (t = –7.160, p = 0.000 &lt; 0.01), while there was a significant positive correlation between the length of service time on board and overall fatigue (t = 3.474, p = 0.001 &lt; 0.01).ConclusionThe results indicated that a reasonable vacation schedule was crucial for the relief of the seafarers’ fatigue, and also played a positive role in the state of working on the ship again.
Prevalence and Associated Risk Factors of Suicidal Ideation Among Brazilian Pregnant Women: A Population-Based Study
Authors: Faisal-Cury Alexandre , Oliveira Rodrigues Daniel Maurício , Matijasevich Alicia , Tarpinian Fernanda , Tabb Karen 
Published: March 2022

BackgroundSuicide is a leading cause of death during the perinatal period in high-income countries (HIC). There remains a lack of population-based studies about suicidal ideation (SI) during pregnancy among low and middle income countries (LMIC).Objective(s)Using the case of Brazil, we aim to estimate the prevalence of SI during pregnancy and its association with antenatal depression (AD) and sociodemographic factors in a LMIC.MethodWe used data from the Brazilian National Survey (PNS-2019), a population-based study, with a complex and probabilistic sampling method. Of the 27,136 women of reproductive age (15 to 49 years old) who participated in the PNS, a total of 769 women reported being pregnant at the time of the interview. All PNS participants answered the Patient Health Questionnaire-9 (PHQ-9) and a questionnaire with sociodemographic data. SI was defined as any answer to the PHQ-9 item 9 other than 0 (not at all). Logistic regression models were performed to obtain crude and adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) for the association between explanatory variables and SI during pregnancy.ResultsAmong 769 women, 33 (3.9%, 95% CI: 3.0–5.1%) reported SI during pregnancy. In the adjusted analysis, higher odds of SI were associated with being 20 to 34 years old (aOR:0.24, 95% CI: 0.08–0.74) or 35 to 49 years old (aOR:0.15; 95% CI: 0.04–0.50), having 9 to 11 years of education (aOR 0.23, 95% CI: 0.61–0.86), acheiving the highest family income category (aOR:0.08, 95% CI: 0.01–0.58), not living in the South/Southeast regions of Brazil (aOR:5.52, 95% CI: 2.36–12.9), and having probable mild AD (aOR:10.5 95% CI: 2.3–47.9) or moderate AD (aOR:241.3, 95% CI: 58.4–996.7).Conclusion(s)In Brazil, SI affects almost 4% of pregnant women and is associated with sociodemographic vulnerability. Clinically, women with mild symptoms of depression may also experience SI during pregnancy. These findings are important for designing effective perinatal mental health interventions in LMICs.
Label-Free Determination of PSA and Free PSA Using MA-SERS
Authors: Chaloupková Zuzana , Medříková Zdenka , Král Milan , Šedajová Veronika , Ranc Václav 
Published: March 2022

Prostate cancer is one of the compelling types of cancer diagnosed in men. Development of screening analytical methods, which provide fast and reliable results is, thus, demanding. Currently applied methods are usually based on the determination of serum prostate-specific antigen (PSA), where several limitations were identified. However, scientific reports have shown a direct correlation between the percentage of free PSA and prostate volume, and indirect correlation between the unfavorable course of the disease of prostate cancer and the percentage of free PSA in men with elevated PSA levels. Parallel analysis of PSA and free PSA presents an interesting alternative. Here, we present a new analytical method for a parallel analysis of PSA and free PSA in a whole human blood based on MA-SERS. The method is based on magnetic Fe3O4@Ag nanocomposite functionalized using anti-PSA. The method can distinguish between levels of PSA and free PSA within a single analytical run with limits of detection of 0.62 ng/ml for PSA and 0.49 ng/ml for free PSA, respectively.
Mobility Disability and Exercise: Health Outcomes of an Accessible Community-Based Center
Authors: Morgan Kerri A. , Taylor Kelly L. , Walker Carla Wilson , Tucker Susan , Dashner Jessica L. , Hollingsworth Holly 
Published: March 2022

ObjectiveThe purpose of this study was to determine how support and guidance provided by trained professionals during a 12-week, community-based transition exercise program, impact health outcomes and continued engagement in physical activity for persons with a mobility disability (PwMD).DesignA single arm pre-post design was used.SettingAccessible community-based health and wellness center.ParticipantsThe study included 244 PwMD using a mobility device.InterventionsParticipants completed a 12-week transition exercise program provided through an accessible community facility that provided education and support to complete endurance and strength related exercises as well as programming to encourage transition to self-directed engagement in exercise.Main Outcome MeasuresBodyweight, BMI, pain, perceived exertion, speed, and distance during cardiovascular fitness testing, and strength were measured pre and post exercise program. The number of participants that signed up for a monthly membership after the program was also monitored.ResultsFor the total group, average pain reported over previous 30 days decreased significantly (p &lt; 0.01), current daily pain decreased significantly (p &lt; 0.05), perceived exertion at the end of the 9-min endurance test decreased significantly (p &lt; 0.05), and the four upper extremity strength exercises showed large, significant strength gains (p &lt; 0.01) after the program. There was no significant change in bodyweight, BMI, or speed and distance completed during endurance testing. At the completion of the program, 76% of participants enrolled in a monthly membership at the facility with the intentions to continue to exercise regularly.ConclusionsThis study provides evidence that an accessible community-based exercise program, with a transitional component supported by trained professionals, can support the exercise goals of PwMD and improve strength, decrease pain, and may promote regular exercise adoption for PwMD.
Storm-Time Evolution of the Equatorial Electron Pitch Angle Distributions in Earth’s Outer Radiation Belt
Authors: Smirnov Artem , Shprits Yuri , Allison Hayley , Aseev Nikita , Drozdov Alexander , Kollmann Peter , Wang Dedong , Saikin Anthony A. 
Published: March 2022

In this study we analyze the storm-time evolution of equatorial electron pitch angle distributions (PADs) in the outer radiation belt region using observations from the Magnetic Electron Ion Spectrometer (MagEIS) instrument aboard the Van Allen Probes in 2012–2019. The PADs are approximated using a sum of the first, third and fifth sine harmonics. Different combinations of the respective coefficients refer to the main PAD shapes within the outer radiation belt, namely the pancake, flat-top, butterfly and cap PADs. We conduct a superposed epoch analysis of 129 geomagnetic storms and analyze the PAD evolution for day and night MLT sectors. PAD shapes exhibit a strong energy-dependent response. At energies of tens of keV, the PADs exhibit little variation throughout geomagnetic storms. Cap PADs are mainly observed at energies<300 keV, and their extent in L shrinks with increasing energy. The cap distributions transform into the pancake PADs around the main phase of the storm on the nightside, and then come back to their original shapes during the recovery phase. At higher energies on the dayside, the PADs are mainly pancake during pre-storm conditions and become more anisotropic during the main phase. The quiet-time butterfly PADs can be observed on the nightside at L>5.6. During the main phase, butterfly PADs have stronger 90°-minima and can be observed at lower L-shells (down to L = 5), then transitioning into flat-top PADs at L ∼ 4.5 – 5 and pancake PADs at L<4.5. The resulting PAD coefficients for different energies, locations and storm epochs can be used to test the wave models and physics-based radiation belt codes in terms of pitch angle distributions.
Neuroglial activity in the focus of ischemic stroke
Authors: Kalinichenko S. G. , Korobtsov A. V. , Matveeva N. Yu. , Matveev Yu. A. 
Published: March 2022

Objective: To study the dynamics of morphochemical modifications in glial cells of rat neocortex under the conditions of experimental stroke, induced by means of constant occlusion of the middle brain artery.Methods: We studied the immunolocalisation of glial cell-derived neurotrophic factor (GDNF), glial fibrillary acidic protein (GFAP), Iba-1 and S-100 in the rat parietal cortex during the constant occlusion of middle brain artery.Results: Astrocytes, expressing GFAP and S-100, are found in the penumbra area and define its borders. In the later stages of stroke, the density of astrocytes increases on the border of the stroke focus and decreases around penumbra, which leads to immunoreactive perifocal zone boarders shifting and its significant narrowing. The reversion of immunoreactivity during the early and late stages of stroke was observed. The reversion was defined by decrease in S-100-expression in astrocytes and expression presence in pyramidal neurons on the 1-3 day of ischemia in the stroke focus. The reverse tendency toward localization changes of GDNF from neurons to astrocytes was detected in penumbra on 8-21 day. Iba-1-reactive microglia at the stroke’s core shows the sings of activated macrophages - increase in the cells’ size, reduction in quantity and branching. Iba-1-reactive microglia concentrates in the stroke focus, reaching its highest point on the 8 day and corresponds to decreasing spatial density of astrocytes in the penumbra area.Conclusions. Specificity of the morphochemical alteration of glial cells closely interacts with the condition of neurons in the stroke focus, points to the penumbra borders and connected with the balance of various protective and neurodestructive processes.