bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chuanxiong improves angiogenesis via the PI3K/AKT/Ras/MAPK pathway based on network pharmacology and DESI-MSI metabolomics
Authors: Cheng Xue-hao , Yang Xue-xin , Cui He-rong , Zhang Bei-bei , Chen Ke-dian , Yang Xiao-yun , Jiao Jing-yi , Du Ya-wen , Zhang Qi , Zheng Jia-xin , Xie Wei , Li Fei-fei , Lei Hai-min 
Published: May 2023

Introduction: Chuanxiong, a traditional Chinese medicine, has been proved to treat a variety of cardiovascular and cerebrovascular diseases by promoting angiogenesis. However, the mechanisms of Chuanxiong’s pro-angiogenesis is currently unknown. This study aimed to uncover the effect and mechanisms of Chuanxiong promoting angiogenesis in vivo and in vitro.Methods: First, potential targets were predicted by network pharmacology analysis, and PPI network was established and the pathways were enriched. Then, the chorioallantoic membrane test on quails was applied to assess the proangiogenic effects in vivo. As well, to evaluate the effects in vitro, real-time PCR, western blot analysis, the scratch test, and the tube formation experiment were used. Subsequently, the major metabolic pathways were analyzed using non-targeted metabolomics.Results: As a result of network pharmacological analysis, 51 collective targets of Chuanxiong and angiogenesis were identified, which are mainly associated with PI3K/AKT/Ras/MAPK pathway. And the biological verification results showed that Chuanxiong could increase the vessel numbers and vessel area in qCAM models. Meanwhile, Chuanxiong contributed to HUVEC proliferation, tube formation, migration, by encouraging scratch healing rates and boosting tube branch points. In addition, the levels of VEGFR2, MAPK and PI3K were elevated compared to the control group. The western blot analysis also confirmed Chuanxiong could promote an increase in AKT, FOXO1 and Ras. Furtheremore, metabolomic results showed that the proangiogenic effect of Chuanxiong is associated with glycine, serine and threonine metabolism.Discussion: In conclusion, this study clarified that Chuanxiong could promote angiogenesis in vivo and in vitro via regulating PI3K/AKT/Ras/MAPK pathway.
The price and affordability of essential medicines, progress and regional distribution in China: a systematic review
Authors: Liu Zheng , Zou Kun , Liu Dan , Zhang Miao , Shi Yuqing , Chen Zhe , Lang Bingchen , Cheng Xiao , Li Hailong , Zeng Linan , Tang Yong , Zhao Shaoyang , Choonara Imti , Jiang Yongmu , Zhang Lingli 
Published: May 2023

Background: Essential medicine is a vital component to assure universal access to quality healthcare. However, the trend of affordability to essential medicines in China and its regional differences were not yet fully understood. This study aimed to systematically evaluate the price and affordability of essential medicines, their progress, and regional distribution in China in the last decades.Methods: We searched seven databases and three websites for potentially eligible studies from inception until March 2022. Studies on the price and affordability of essential medicines investigated in China were included. Median and interquartile range (IQR) was used to describe the price and affordability of essential medicines, and compared in three periods, before 2009, from 2009 to 2014, and from 2015 to 2019. Subgroup analysis was performed to examine the price and affordability by regions, health facilities, and ATC categories of medicines. The study was registered with PROSPERO (CRD42022310173).Results: A total of 65 studies including 11,639 health facilities investigated between 2006 and 2019 were included in this review. Median price ratios (MPR) and affordability of essential medicines were reported in 44 studies and 50 studies, respectively. The median MPRs of essential medicines in China was 1.59 (IQR: 5.39), with a tendency to rise first and then fall from 2006 to 2019. And the median affordability was equal to 0.88 (IQR: 2.58) days’ wage of the lowest paid unskilled government worker, but steadily rose from 2006 to 2019. Subgroup analysis showed that the affordability in the western region (1.40, IQR: 2.88), urban area (0.95, IQR: 2.80), private sector (0.90, IQR: 2.30), of originator brands (OB) (2.90, IQR: 6.68), and antineoplastic and immunomodulating agents (5.68, IQR: 56.47) were worse than their counterparts.Conclusion: The prices of essential medicine were higher than international level, the overall affordability of essential medicines in China is acceptable but poor in the western region, for OB drugs and anti-cancer medicines. Further national essential medicine policies are needed to reduce regional disparities and improve the affordability of expensive drugs.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/#recordDetails
Efficacy of a paper-based interleukin-6 test strip combined with a spectrum-based optical reader for sequential monitoring and early recognition of respiratory failure in elderly pneumonia—a pilot study
Authors: Chen Cheng-Han , Fu Yi-Chen , Lee Yi-Tzu , Hsieh Kai-Sheng , Shen Ching-Fen , Cheng Chao-Min 
Published: May 2023

Introduction: Community-acquired pneumonia (CAP) is lethal in elderly individuals who are more vulnerable to respiratory failure and require more emergency ventilation support than younger individuals. Interleukin-6 (IL-6) plays a crucial role and has predictive value in CAP; high serum IL-6 concentrations in adults are associated with high respiratory failure and mortality rates. Early detection of IL-6 concentrations can facilitate the timely stratification of patients at risk of acute respiratory failure. However, conventional enzyme-linked immunosorbent assay (ELISA) IL-6 measurement is laborious and time-consuming.Methods: The IL-6 rapid diagnostic system combined with a lateral flow immunoassay-based (LFA-based) IL-6 test strip and a spectrum-based optical reader is a novel tool developed for rapid and sequential bedside measurements of serum IL-6 concentrations. Here, we evaluated the correlation between the IL-6 rapid diagnostic system and the ELISA and the efficacy of the system in stratifying high-risk elderly patients with CAP. Thirty-six elderly patients (median age: 86.5 years; range: 65–97 years) with CAP were enrolled. CAP diagnosis was established based on the Infectious Diseases Society of America (IDSA) criteria. The severity of pneumonia was assessed using the CURB-65 score and Pneumonia Severity Index (PSI). IL-6 concentration was measured twice within 24 h of admission.Results: The primary endpoint variable was respiratory failure requiring invasive mechanical or non-invasive ventilation support after admission. IL-6 rapid diagnostic readouts correlated with ELISA results (p &lt; 0.0001) for 30 samples. Patients were predominantly male and bedridden (69.4%). Ten patients (27.7%) experienced respiratory failure during admission, and five (13.9%) died of pneumonia. Respiratory failure was associated with a higher mortality rate (p = 0.015). Decreased serum IL-6 concentration within 24 h after admission indicated a lower risk of developing respiratory failure in the later admission course (Receiver Operating Characteristic [ROC] curve = 0.696).Conclusion: Sequential IL-6 measurements with the IL-6 rapid diagnostic system might be useful in early clinical risk assessment and severity stratification of elderly patients with pneumonia. This system is a potential point-of-care diagnostic device for sequential serum IL-6 measurements that can be applied in variable healthcare systems.
An ultrasound assisted, ionic liquid-molecular iodine synergy driven efficient green synthesis of pyrrolobenzodiazepine-triazole hybrids as potential anticancer agents
Authors: Saquib Mohammad , Ahamad Shakir , Khan Mohammad Faheem , Khan Mohammad Imran , Hussain Mohd Kamil 
Published: May 2023

Herein, we report an efficient and eco-friendly, ultrasound assisted synthetic strategy for the construction of diversified pyrrolobenzodiazepine-triazole hybrids, which are potentially pharmaceutically important scaffolds, via a domino reaction involving intermolecular electrophilic substitution followed by intramolecular Huisgen 1,3-dipolar azide-alkyne cycloaddition. The USP of the reported protocol is the use of benign and inexpensive, recyclable molecular iodine-ionic liquid synergistic catalytic system cum reaction media for achieving the synthesis. The other salient features of this method are the use of mild reaction conditions, high yield and atom economy, operational simplicity, broad substrate scope and easy workup and purification. All the synthesized compounds were evaluated for in vitro anti-proliferative activity against various cancer cell lines. From among the synthesized title compounds, 9,9-dimethyl-8-phenyl-9H-benzo [b]pyrrolo [1,2-d][1,2,3]triazolo[5,1-g][1,4]diazepine (7) was found most to be the most active compound exhibiting IC50 value of 6.60, 5.45, 7.85, 11.21, 12.24, 10.12, and 11.32 µM against MCF-7, MDA-MB-231, HeLa, SKOV-3, A549, HCT-116 and DLD-1 cell lines, respectively. Further the compounds were found to be non-toxic against normal human embryonic kidney (HEK-293) cell line.
QSAR and molecular docking studies on designing potent inhibitors of SARS-CoVs main protease
Authors: Song Fucheng , Sun Haoyang , Ma Xiaofang , Wang Wei , Luan Mingyuan , Zhai Honglin , Su Guanmin , Liu Yantao 
Published: May 2023

Background: Severe acute respiratory syndrome coronavirus (SARS-CoVs) have emerged as a global health threat, which had caused a high rate of mortality. There is an urgent need to find effective drugs against these viruses.Objective: This study aims to predict the activity of unsymmetrical aromatic disulfides by constructing a QSAR model, and to design new compounds according to the structural and physicochemical attributes responsible for higher activity towards SARS-CoVs main protease.Methods: All molecules were constructed in ChemOffice software and molecular descriptors were calculated by CODESSA software. A regression-based linear heuristic method was established by changing descriptors datasets and calculating predicted IC50 values of compounds. Then, some new compounds were designed according to molecular descriptors from the heuristic method model. The compounds with predicted values smaller than a set point were constantly screened out. Finally, the properties analysis and molecular docking were conducted to further understand the structure-activity relationships of these finalized compounds.Results: The heuristic method explored the various descriptors responsible for bioactivity and gained the best linear model with R2 0.87. The success of the model fully passed the testing set validation, proving that the model has both high statistical significance and excellent predictive ability. A total of 5 compounds with ideal predicted IC50 were found from the 96 newly designed derivatives and their properties analyze was carried out. Molecular docking experiments were conducted for the optimal compound 31a, which has the best compound activity with good target protein binding capability.Conclusion: The heuristic method was quite reliable for predicting IC50 values of unsymmetrical aromatic disulfides. The present research provides meaningful guidance for further exploration of the highly active inhibitors for SARS-CoVs.
Development, growth and metabolic effects in stage IV lobster (Homarus americanus) following chronic exposure to sediments spiked with commercial formulations of deltamethrin and permethrin
Authors: Daoud Dounia , Greenwood Spencer J. , de Jourdan Benjamin , Asnicar Davide , Taylor Laura J. 
Published: May 2023

Coastal and estuarine ecosystems are environments heavily influenced by natural and anthropogenic activities. Chemicals used for pest control in agriculture and aquaculture may accumulate in natural coastal environments. Pyrethroids are common pesticides that are used on crops as well as applied to aquaculture pens and then may disperse in the surrounding ocean once treatment is complete. This study observed the sublethal effects of two pyrethroids, permethrin and deltamethrin (within commercially available formulations), on post-larval stage IV American lobster (Homarus americanus) using growth parameters and metabolic rate as indicators. Observed effects on growth parameters were a decrease in size increment and specific growth rate as well as an increase in intermolt period in stage IV lobsters exposed to 100 μg/kg permethrin. No significant differences were found for intermolt period, size increment, or specific growth rate in deltamethrin-exposed stage IV lobsters. Metabolic rates were not significantly different between deltamethrin-exposed and control lobsters, however, this sublethal effect warrants further investigation. Collectively, these results represent the first examination of the sublethal effects of exposure to pyrethroids formulations in post-larval lobsters, highlighting the potential for effects on non-target marine organisms.
Optogenetic manipulation of cardiac repolarization gradients using sub-threshold illumination
Authors: Marchal Gerard A. , Biasci Valentina , Loew Leslie M. , Biggeri Annibale , Campione Marina , Sacconi Leonardo 
Published: May 2023

Introduction: Mechanisms underlying cardiac arrhythmias are typically driven by abnormalities in cardiac conduction and/or heterogeneities in repolarization time (RT) across the heart. While conduction slowing can be caused by either electrophysiological defects or physical blockade in cardiac tissue, RT heterogeneities are mainly related to action potential (AP) prolongation or abbreviation in specific areas of the heart. Importantly, the size of the area with altered RT and the difference between the short RT and long RT (RT gradient) have been identified as critical determinators of arrhythmogenicity. However, current experimental methods for manipulating RT gradient rely on the use of ion channel inhibitors, which lack spatial and temporal specificity and are commonly only partially reversible. Therefore, the conditions facilitating sustained arrhythmia upon the presence of RT heterogeneities and/or defects in cardiac conduction remain to be elucidated.Methods: We here employ an approach based on optogenetic stimulation in a low-intensity fashion (sub-threshold illumination), to selectively manipulate cardiac electrical activity in defined areas of the heart.Results: As previously described, subthreshold illumination is a robust tool able to prolong action potentials (AP), decrease upstroke velocity as well as slow cardiac conduction, in a fully reversible manner. By applying a patterned sub-threshold illumination in intact mouse hearts constitutively expressing the light-gated ion channel channelrhodopsin-2 (ChR2), we optically manipulate RT gradients and cardiac conduction across the heart in a spatially selective manner. Moreover, in a proof-of-concept assessment we found that in the presence of patterned sub-threshold illumination, mouse hearts were more susceptible to arrhythmias. Hence, this optogenetic-based approach may be able to mimic conduction slowing and RT heterogeneities present in pathophysiological conditions.
Learning digital skills online: empowering older adults through one-to-one, online digital training provision
Authors: Wilson-Menzfeld Gemma , Gates Jessica Raven , Moreland Mary , Raw Helen , Johnson Amy 
Published: May 2023

IntroductionDigital exclusion, through lack of access and poor digital skills, can have an adverse impact on daily living. Not only did the COVID-19 pandemic dramatically impact the necessity of technology in our daily lives, but also reduced the availability of digital skills programmes. This study aimed to explore perceived facilitators and barriers of a digital skills programme that was delivered remotely (online) and to reflect on this form of training as a possible alternative to traditional face-to-face models.MethodsIndividual interviews were carried out with programme participants and the programme instructor.ResultsTwo themes were generated from this data: (a) Creating a unique learning environment; and (b) Encouraging further learning.DiscussionBarriers to digital delivery were evident, however, the individual and personalized delivery empowered participants within their own learning, supporting individuals to learn skills relevant to them and to continue their digital learning journey.
Working-from-home persistently influences sleep and physical activity 2 years after the Covid-19 pandemic onset: a longitudinal sleep tracker and electronic diary-based study
Authors: Massar Stijn A. A. , Ong Ju Lynn , Lau TeYang , Ng Ben K. L. , Chan Lit Fai , Koek Daphne , Cheong Karen , Chee Michael W. L. 
Published: May 2023

ObjectiveWorking from home (WFH) has become common place since the Covid-19 pandemic. Early studies observed population-level shifts in sleep patterns (later and longer sleep) and physical activity (reduced PA), during home confinement. Other studies found these changes to depend on the proportion of days that individuals WFH (vs. work from office; WFO). Here, we examined the effects of WFH on sleep and activity patterns in the transition to normality during the later stages of the Covid-19 pandemic (Aug 2021–Jan 2022).MethodsTwo-hundred and twenty-five working adults enrolled in a public health study were followed for 22  weeks. Sleep and activity data were collected with a consumer fitness tracker (Fitbit Versa 2). Over three 2-week periods (Phase 1/week 1–2: August 16–29, 2021; Phase 2/week 11–12: October 25–November 7, 2021; Phase 3/week 21–22: January 3–16, 2022), participants provided daily Fitbit sleep and activity records. Additionally, they completed daily phone-based ecological momentary assessment (EMA), providing ratings of sleep quality, wellbeing (mood, stress, motivation), and information on daily work arrangements (WFH, WFO, no work). Work arrangement data were used to examine the effects of WFH vs. WFO on sleep, activity, and wellbeing.ResultsThe proportion of WFH vs. WFO days fluctuated over the three measurement periods, mirroring evolving Covid restrictions. Across all three measurement periods WFH days were robustly associated with later bedtimes (+14.7 min), later wake times (+42.3 min), and longer Total Sleep Time (+20.2 min), compared to WFO days. Sleep efficiency was not affected. WFH was further associated with lower daily step count than WFO (−2,471 steps/day). WFH was associated with higher wellbeing ratings compared to WFO for those participants who had no children. However, for participants with children, these differences were not present.ConclusionPandemic-initiated changes in sleep and physical activity were sustained during the later stage of the pandemic. These changes could have longer term effects, and conscious effort is encouraged to harness the benefits (i.e., longer sleep), and mitigate the pitfalls (i.e., less physical activity). These findings are relevant for public health as hybrid WHF is likely to persist in a post-pandemic world.
The use of artificial intelligence in a military context: development of the attitudes toward AI in defense (AAID) scale
Authors: Hadlington Lee , Binder Jens , Gardner Sarah , Karanika-Murray Maria , Knight Sarah 
Published: May 2023

IntroductionThe use of artificial intelligence (AI) for national defense is a matter of high societal significance and ongoing public discourse, but very little is known about public acceptance of AI in defense contexts. Currently, there is no reliable and valid measure of attitudes towards AI in defense, and more general attitudinal measures on AI use are unlikely to capture relevant perceptions and opinions. A measure was therefore developed for the assessment of Attitudes towards AI in Defense (AAID), and this work presents the initial validation of this scale.MethodsA total of 1,590 participants (aged 19-75, M = 45.7, SD = 16.1) completed a self-report questionnaire which included an initial item pool of 29 attitudinal statements related to the use of AI in defense. An additional general attitude towards AI scale was also included to assess the concurrently validity of the AAID scale. The AAID underwent initial statistical validation via exploratory factor analysis and confirmatory factor analysis to test the underlying structure of the newly developed scale.ResultsItems reduction and exploratory factor analysis resulted in a final scale consisting of 15 items. A final two factor solution explained 42.52% of the variance (Factor 1 = 22.35%, Factor 2 = 20.17%). Factor 1 was termed “Positive outcomes” and reflected the potential and anticipated consequences of implementing AI in defense. Factor 2 was termed “Negative Outcomes” and reflected the potential negative outcomes for AI in defense. The scale also exhibited acceptable internal reliability and current validity.DiscussionThe newly developed AAID presents a new measurement tool which has the capacity to assess current attitudes towards AI in defense. Such work is essential if further developments in AI in defense are to continue with the support of the public. However, the work also notes that there are some key concerns and barriers that could block further developments in the area, with further work needed to explore how such anxieties are driven by narratives related to the topic.
Suicidal ideation, attempt and associated factor among secondary school students in Harari regional state, Eastern Ethiopia. A multi-center cross-sectional study
Authors: Bete Tilahun , Birhanu Abdi , Negash Abraham , Yadeta Elias , Lemi Magarsa , Balcha Tegenu , Sertsu Addisu , Birhanu Bekelu , Nigussie Shambel , Gemechu Kabtamu , Meseret Fentahun , Mohammed Hanan , Alemu Addisu , Dechasa Deribe Bekele , Asmerom Haftu , Arkew Mesay , Shewangizaw Abayneh , Mohamed Ahmed , Ahemed Fila , Wodaje Dawud , Dessie Yadeta , Debella Adera , Getachew Tamirat , Nigussie Kabtamu , Eyeberu Addis 
Published: May 2023

BackgroundSuicide is a major public health issue across the globe. It is the second leading cause of death in adolescents. Even though the rate of suicide has increased, no study has been conducted to investigate the determinants of suicide in the study area. Therefore, this study aimed to assess the magnitude of suicidal ideation, suicide attempts, and its associated factors among secondary school students in the Harari regional state of Eastern Ethiopia.MethodsAn institutional-based cross-sectional study was conducted among randomly selected 1,666 secondary school students. A structured-self-administered questionnaire was used for data collection. The WHO Composite International Diagnostic Interview (CIDI) was used to assess suicidal ideation and suicide attempts. The Depression Anxiety and Stress Scale (DASS) was also used to assess depression, anxiety, and stress. Data were entered into EpiData version 3.1 and exported to Stata version 14.0 for the analysis. A logistic regression analysis was performed to determine the association between the outcome and independent variables and the statistical significance was declared at a p-value of &lt; 0.05.ResultThe overall magnitude of suicidal ideation and attempts was 13.82% at 95% confidence interval (CI): 12.16–15.66 and 7.61% at 95% CI: 6.37–9.07, respectively. Suicidal ideations and suicide attempts were significantly associated with undergoing depressive symptoms (adjusted odds ratio [AOR]: 1.54; 95% CI: 1.08–2.19 and AOR: 2.37; 95% CI: 1.46–3.86, respectively), experiencing anxiety symptoms (AOR: 1.80; 95% CI: 1.25–2.59 and AOR: 1.89; 95% CI: 2.14–10.65, respectively), being exposed to sexual violence (AOR: 3.36; 95% CI: 1.65–6.84), and having a family history of suicidal attempts (AOR: 2.12; 95% CI: 1.21–3.69 and AOR: 4.74; 95% CI: 2.14–10.65, respectively), whereas living in a rural residence (AOR: 1.65 95%, CI: 1.08–2.55) was significantly associated only with suicide attempts.Conclusion and recommendationsNearly one in six secondary school students had both suicidal ideation and attempted to take their own life. Suicide is one of the psychiatric emergencies that need immediate action. Therefore, the concerned body from either a governmental or a non-governmental organization should work in setting strategies to minimize sexual violence as well as depressive and anxiety symptoms.