bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neonatal pain assessment: Do we have the right tools?
Authors: Llerena Amelia , Tran Krystal , Choudhary Danyal , Hausmann Jacqueline , Goldgof Dmitry , Sun Yu , Prescott Stephanie M. 
Published: February 2023

BackgroundThe assessment and management of neonatal pain is crucial for the development and wellbeing of vulnerable infants. Specifically, neonatal pain is associated with adverse health outcomes but is often under-identified and therefore under-treated. Neonatal stress may be misinterpreted as pain and may therefore be treated inappropriately. The assessment of neonatal pain is complicated by the non-verbal status of patients, age-dependent variation in pain responses, limited education on identifying pain in premature infants, and the clinical utility of existing tools.ObjectiveWe review research surrounding neonatal pain assessment scales currently in use to assess neonatal pain in the neonatal intensive care unit.MethodsWe performed a systematic review of original research using PRISMA guidelines for literature published between 2016 and 2021 using the key words “neonatal pain assessment” in the databases Web of Science, PubMed, and CINAHL. Fifteen articles remained after review, duplicate, irrelevant, or low-quality articles were eliminated.ResultsWe found research evaluating 13 neonatal pain scales. Important measurement categories include behavioral parameters, physiological parameters, continuous pain, acute pain, chronic pain, and the ability to distinguish between pain and stress. Provider education, inter-rater reliability and ease of use are important factors that contribute to an assessment tool's success. Each scale studied had strengths and limitations that aided or hindered its use for measuring neonatal pain in the neonatal intensive care unit, but no scale excelled in all areas identified as important for reliably identifying and measuring pain in this vulnerable population.ConclusionA more comprehensive neonatal pain assessment tool and more provider education on differences in pain signals in premature neonates may be needed to increase the clinical utility of pain scales that address the different aspects of neonatal pain.
Glutamine ameliorates hyperoxia-induced hippocampal damage by attenuating inflammation and apoptosis via the MKP-1/MAPK signaling pathway in neonatal rats
Authors: Xuan Chouhui , Cui Haixia , Jin Zhengyong , Yue Yuyang , Cao Shuxia , Cui Songbiao , Xu Dongyuan 
Published: February 2023

Glutamine (Gln) is an immunomodulatory protein that mediates oxidative stress, inflammation, and apoptosis, but has not been reported in the treatment of hyperoxia (Hyp)-induced brain injury. The aim of this study was to determine whether Gln could improve hyp-induced brain injury in neonatal rats to and later learning and memory dysfunction, and to explore its possible mechanisms. We prepared a model of neonatal rat brain injury caused by normobaric hyperoxia while administered with Gln for 7 days for evaluation. Learning memory function was assessed with the Morris water maze test. Histological analysis, protein expression analysis, oxidative stress and inflammation level analysis were performed using hippocampal tissue. Gln treatment significantly reduced brain tissue water content, oxidative stress levels, microglia activation and inflammatory factor expression, and attenuated tissue damage and apoptosis in the hippocampal region. Gln ameliorates hyp-induced learning, memory impairment in neonatal rats in water maze test. It also increased MKP-1 protein expression and decreased p-p38, p-ERK and p-JNK. Therefore, it is hypothesized that Gln may exert neuroprotective effects by increasing MKP-1 expression to negatively regulate MAPK signaling, with potential cognitive improvement in hyp-induced brain injury.
Wound healing properties of a new formulated flavonoid-rich fraction from Dodonaea viscosa Jacq. leaves extract
Authors: Subramanian Shanthi , Duraipandian Chamundeeswari , Alsayari Abdulrhman , Ramachawolran Gobinath , Wong Ling Shing , Sekar Mahendran , Gan Siew Hua , Subramaniyan Vetriselvan , Seethalakshmi S , Jeyabalan Srikanth , Dhanasekaran Sivaraman , Chinni Suresh V. , Mat Rani Nur Najihah Izzati , Wahab Shadma 
Published: February 2023

Background:Dodonaea viscosa Jacq. (D. viscosa) belongs to the family of Sapindaceae, commonly known as “Sinatha,” and is used as a traditional medicine for treating wounds due to its high flavonoids content. However, to date there is no experimental evidence on its flavonoid-rich fraction of D. viscosa formulation as an agent for healing wounds.Objective: The present study aimed to evaluate the wound healing effect of ethyl acetate fraction of D. viscosa leaves on dermal wounds.Methods: The ethyl acetate fraction was produced from a water-ethanol extract of D. viscosa leaves and was quantitatively evaluated using the HPLC technique. The in-vivo wound healing ability of the ethyl acetate fraction of D. viscosa ointment (DVFO, 2.5%w/w and 5%w/w) was investigated in Sprague-Dawley rats utilizing an incision and excision paradigm with povidone-iodine ointment (5% w/w) as a control. The percentage of wound closure, hydroxyproline and hexosamine concentrations, tensile strength and epithelialization duration were measured. Subsequently, histopathology analysis of skin samples as well as western blots were performed for collagen type 3 (COL3A1), basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF).Results: The ethyl acetate fraction of D. viscosa revealed flavonoids with high concentrations of quercetin (6.46% w/w) and kaempferol (0.132% w/w). Compared to the control group, the DVFO (2.5% and 5.0% w/w) significantly accelerated wound healing in both models, as demonstrated by quicker wound contraction, epithelialization, elevated hydroxyproline levels and increased tensile strength. Histopathological investigations also revealed that DVFO treatment improved wound healing by re-epithelialization, collagen formation and vascularization of damaged skin samples. Western blot analysis further demonstrated an up-regulation of COL3A, vascular endothelial growth factor and bFGF protein in wound granulation tissue of the DVFO-treated group (p &lt; 0.01).Conclusion: It is concluded that flavonoid-rich D. viscosa ethyl acetate fraction promotes wound healing by up-regulating the expressions of COL3A, VEGF and bFGF protein in wound granulation tissue. However, extensive clinical and pre-clinical research on the flavonoid-rich fraction of D. viscosa is needed to determine its significant impact in the healing of human wounds.
Anticholinergic effect of resveratrol with vitamin E on scopolamine-induced Alzheimer’s disease in rats: Mechanistic approach to prevent inflammation
Authors: Foudah Ahmed I. , Devi Sushma , Alam Aftab , Salkini Mohammad Ayman , Ross Samir A. 
Published: February 2023

The most common form of dementia, Alzheimer’s disease (AD), is characterized by gradual declines in cognitive abilities and behavior. It is caused by a combination of factors, including amyloid-β (Aβ) accumulation, acetylcholine (ACh) loss, oxidative stress, and inflammation. Phenolic compounds have a variety of health benefits, including antioxidant activities. Thus, the purpose of this study was to investigate how resveratrol (RES) alone and in combination with vitamin E affected rats with AD using scopolamine (SCO). Animals are categorized into groups; (i) control, (ii) SCO (1 mg/kg i.p.), (iii) SCO + donepezil, (iv) SCO + RES (50 mg/kg, p.o.), (v) SCO + RES (75 mg/kg, p.o.), (vi) SCO + RES (50 mg/kg + vitamin E 1 mg/kg, p.o.) for 17 days. In rats, studied behavioural (NOR and EPM) and biochemical characteristics. In addition, brain histopathology was examined to investigate any damage to the hippocampus and neuroprotection. SCO-induced changes in acetylcholinesterase, protein carbonyl, and TNF-α improved after resveratrol treatment. RES increased antioxidant levels, decreased SCO-induced lipid peroxidation, and reversed SCO-mediated changes compared with the drug donepezil. The results indicated that RES and vitamin E had nootropic action in the NOR and EPM tests, measured by the recognition index and the inflection ratio. This study supports the efficacy of RES as a preventive and treatment agent for AD. Vitamin E showed a synergistic effect on RES, which helps in managing cognitive impairment AD.
Role of ferroptosis in hypoxic preconditioning to reduce propofol neurotoxicity
Authors: Chen Jing , Xiao Fei , Chen Lifei , Zhou Zhan , Wei Yi , Zhong Yu , Li Li , Xie Yubo 
Published: February 2023

Background: An increasing number of studies have reported that neurotoxicity of propofol may cause long-term learning and cognitive dysfunction. Hypoxic preconditioning has been shown to have neuroprotective effects, reducing the neurotoxicity of propofol. Ferroptosis is a new form of death that is different from apoptosis, necrosis, autophagy and pyroptosis. However, it is unclear whether hypoxic preconditioning reduces propofol neurotoxicity associated with ferroptosis. Thus, we aimed to evaluate the effect of propofol on primary hippocampal neurons in vitro to investigate the neuroprotective mechanism of hypoxic preconditioning and the role of ferroptosis in the reduction of propofol neurotoxicity by hypoxic preconditioning.Methods: Primary hippocampal neurons were cultured for 8 days in vitro and pretreated with or without propofol, hypoxic preconditioning, agonists or inhibitors of ferroptosis. Cell counting kit-8, Calcein AM, Reactive oxygen species (ROS), Superoxide dismutase (SOD), Ferrous iron (Fe2+), Malondialdehyde (MDA) and Mitochondrial membrane potential assay kit with JC-1 (JC-1) assays were used to measure cell viability, Reactive oxygen species level, Superoxide dismutase content, Fe2+ level, MDA content, and mitochondrial membrane potential. Cell apoptosis was evaluated using flow cytometry analyses, and ferroptosis-related proteins were determined by Western blot analysis.Results: Propofol had neurotoxic effects that led to decreased hippocampal neuronal viability, reduced mitochondrial membrane potential, decreased SOD content, increased ROS level, increased Fe2+ level, increased MDA content, increased neuronal apoptosis, altered expression of ferroptosis-related proteins and activation of ferroptosis. However, hypoxic preconditioning reversed these effects, inhibited ferroptosis caused by propofol and reduced the neurotoxicity of propofol.Conclusion: The neurotoxicity of propofol in developing rats may be related to ferroptosis. Propofol may induce neurotoxicity by activating ferroptosis, while hypoxic preconditioning may reduce the neurotoxicity of propofol by inhibiting ferroptosis.
Long-term comparative effectiveness and safety of dabigatran, rivaroxaban, apixaban and edoxaban in patients with atrial fibrillation: A nationwide cohort study
Authors: Grymonprez Maxim , De Backer Tine L. , Bertels Xander , Steurbaut Stephane , Lahousse Lies 
Published: February 2023

Background: Although non-vitamin K antagonist oral anticoagulants (NOACs) are recommended over vitamin K antagonists (VKAs) in atrial fibrillation (AF) management, direct long-term head-to-head comparisons are lacking. Therefore, their risk-benefit profiles were investigated compared to VKAs and between NOACs.Methods: AF patients initiating anticoagulation between 2013–2019 were identified in Belgian nationwide data. Inverse probability of treatment weighted Cox regression was used to investigate effectiveness and safety outcomes and were additionally stratified by NOAC dose.Results: Among 254,478 AF patients (328,796 person-years of follow-up), NOACs were associated with significantly lower risks of stroke or systemic embolism (stroke/SE) (hazard ratio (HR) 0.68, 95% confidence interval (CI) (0.64–0.72)), all-cause mortality (HR 0.76, 95%CI (0.74–0.79)), major or clinically relevant non-major bleeding (MB/CRNMB) (HR 0.94, 95%CI (0.91–0.98)) and intracranial hemorrhage (HR 0.73, 95%CI (0.66–0.79)), but non-significantly different risks of myocardial infarction, gastrointestinal and urogenital bleeding compared to VKAs. Despite similar stroke/SE risks, dabigatran and apixaban were associated with significantly lower MB/CRNMB risks compared to rivaroxaban (HR 0.86, 95%CI (0.83–0.90); HR 0.86, 95%CI (0.83–0.89), respectively) and edoxaban (HR 0.91, 95%CI (0.83–0.99); HR 0.86, 95%CI (0.81–0.91), respectively), and apixaban with significantly lower major bleeding risks compared to dabigatran (HR 0.86, 95%CI (0.80–0.92)) and edoxaban (HR 0.79, 95%CI (0.72–0.86)). However, higher mortality risks were observed in some risk groups including with apixaban in patients with diabetes or concomitantly using digoxin compared to dabigatran and edoxaban, respectively.Conclusion: NOACs had better long-term risk-benefit profiles than VKAs. While effectiveness was comparable, apixaban was overall associated with a more favorable safety profile followed by dabigatran.
Sildenafil affects the human Kir2.1 and Kir2.2 channels at clinically relevant concentrations: Inhibition potentiated by low Ba2+
Authors: Iijima Akimasa , Švecová Olga , Hošek Jan , Kula Roman , Bébarová Markéta 
Published: February 2023

Sildenafil (Viagra), the first approved and widely used oral drug for the treatment of erectile dysfunction, was occasionally associated with life-threatening ventricular arrhythmias in patients. Since inward rectifier potassium current (IK1) may considerably contribute to this arrhythmogenesis, we investigated the effect of sildenafil on the human Kir2.1 and Kir2.2, the prevailing subunits forming the ventricular IK1 channels. Experiments were performed by the whole-cell patch clamp technique at 37°C using Chinese hamster ovary cells transiently expressing the human Kir2.1 and Kir2.2 channels. Changes of both the inward and outward current components (at −110 and −50 mV, respectively) were tested to be able to consider the physiological relevance of the sildenafil effect (changes at −110 and −50 mV did not significantly differ, results at −50 mV are listed below). A significant Kir2.1 inhibition was observed at all applied sildenafil concentrations (16.1% ± 3.7%, 20.0% ± 2.6%, and 15.0% ± 3.0% at 0.1, 1, and 10 μM, respectively). The inhibitory effect of 0.1 μM sildenafil was potentiated by the presence of a low concentration of Ba2+ (0.1 μM) which induced only a slight Kir2.1 inhibition by 5.95% ± 0.75% alone (the combined effect was 35.5% ± 3.4%). The subtherapeutic and therapeutic sildenafil concentrations (0.1 and 1 μM) caused a dual effect on Kir2.2 channels whereas a significant Kir2.2 activation was observed at the supratherapeutic sildenafil concentration (10 μM: 34.1% ± 5.6%). All effects were fully reversible. This is the first study demonstrating that sildenafil at clinically relevant concentrations inhibits both the inward and outward current components of the main human ventricular IK1 subunit Kir2.1. This inhibitory effect was significantly potentiated by a low concentration of environmental contaminant Ba2+ in agreement with recently reported data on rat ventricular IK1 which additionally showed a significant repolarization delay. Considering the similar subunit composition of the human and rat ventricular IK1 channels, the observed effects might contribute to sildenafil-associated arrhythmogenesis in clinical practice.
Flexible CsPbCl3 inorganic perovskite thin-film detectors for real-time monitoring in protontherapy
Authors: Bruzzi M. , Calisi N. , Enea N. , Verroi E. , Vinattieri A. 
Published: February 2023

Introduction: This paper deals with the class of versatile semiconducting materials called perovskites, which have been deposited for the first time on flexible substrates and then tested for radiation detection monitoring applications.Methods: Lead halide inorganic perovskite, CsPbCl3, 0.4–1 μm-thick films have been grown on plastic flexible substrates equipped with interdigitated electrodes (IDEs) by magnetron sputtering at room temperature.Results: First measurements in realtime configuration are reported for a 1–µm thick prototype under proton beams with energy in the range 100–228 MeV and 1–10 nA extraction currents, of interest for protontherapy applications.Discussion: Experimental results evidence good performances of our sample as a real-time monitoring device. Current stability under UV and proton beam exposure has been tested in the range 0.1–120 s, as well as reproducibility under multiple exposures. The measured current signal proved to be linearly dependent on the extraction currents at a given proton energy. Linearity of the current signal of the device with proton fluxes was also proved within two order of magnitude range, about 107–109 p/s. These promising results, when coupled with easyness of fabrication, low processing costs and high versatility of electrode configurations, all features characterizing the manufacturing process, put into evidence lead halide perovskites as promising candidates for real-time radiation detection in protontherapy.
Identification of high-risk patients for development of type B aortic dissection based on novel morphological parameters
Authors: Li Da , Wang Jiarong , Zhao Jichun , Wang Tiehao , Zeng Xiangguo , Zheng Tinghui , Yuan Ding 
Published: February 2023

Background: Predicting the development of sporadic type B aortic dissection (TBAD) always remains a difficult issue. This study aimed to identify high-risk patients for development of TBAD based on morphological parameters.Methods: This propensity-score-matched case-control study collected and reconstructed the computed tomography angiography of acute TBAD patients and hospital-based control participants without aortic dissection from January 2013 to December 2016. Multivariate regression analysis was used to calculate the adjusted odds ratio (aOR) and 95% confidence interval (CI). Discriminant and reclassification abilities were compared between our model and a previously established model.Results: Our study included 76 acute TBAD patients and 79 control patients (48 cases and 48 controls after propensity-score matching). The degree of question mark (aOR 1.07, 95% CI 1.04–1.11), brachiocephalic trunk diameter (aOR 1.49, 95% CI 1.20–1.85), brachiocephalic trunk angle (aOR 0.97, 95% CI 0.94–0.99), aortic root diameter (aOR 1.31, 95% CI 1.15–1.48), and aortic width (aOR 1.12, 95% CI 1.07–1.17) were associated with a significantly increased risk of TBAD formation. Similar findings were observed in the propensity-score matching and sensitivity analysis only including hyperacute TBAD patients. A novel prediction model was established based on the aforementioned parameters. The new model showed significantly improved discriminant ability compared with the previously established model (c-index 0.78 [95% CI 0.71–0.85] vs. 0.67 [95% CI 0.58–0.75], p = .03), driven by increased reclassification ability in identifying TBAD patients (NRI for events 0.16, 95% CI 0.02–0.30, p = .02).Conclusion: Morphological predictors, including the degree of question mark, aortic width, aortic root diameter, brachiocephalic trunk angle, and brachiocephalic trunk diameter, may be used to identify patients at high risk of TBAD.
Predicting the growth suitability of Larix principis-rupprechtii Mayr based on site index under different climatic scenarios
Authors: Cheng Ruiming , Zhang Jing , Wang Xinyue , Ge Zhaoxuan , Zhang Zhidong 
Published: February 2023

Larix principis-rupprechtii Mayr (larch) is one of the main afforestation and timber production species used in North China. Climate change has led to a change in its suitable distribution and growth. However, the impact of climate change on its growth suitability is not clear. In this study, using forest resource inventory data and spatially continuous environmental factor data (temperature, precipitation, topography, and soil) in Hebei and Shanxi Provinces, China, the random forest model (RF) was used to simulate the larch site index (SI) and growth suitability under three shared socioeconomic pathways (SSPs: SSP1-2.6, SSP2-4.5, and SSP5-8.5) for the current and future (2021–2040, 2041–2060 and 2080–2100). The results revealed that (1) RF had excellent performance in predicting the regional SI (R2 = 0.73, MAE = 0.93 m, RMSE = 1.35 m); (2) the main factors affecting the productivity of larch were the mean temperature of the warmest quarter (BIO10), elevation (ELEV), mean diurnal range (BIO2), and annual precipitation (BIO12); and (3) larch currently had a higher SI in the Bashang areas and in the high-altitude mountains. The areas characterized as unsuitable, poorly suitable, moderately suitable, and highly suitable accounted for 15.45%, 42.12%, 31.94%, and 10.49% of the total area, respectively. (4) Future climate warming had an obvious inhibitory effect on the SI, and the effect strengthened with increasing radiation intensity and year. (5) The moderately suitable and highly suitable areas of larch growth showed a downward trend under future climate scenarios. By the end of this century, the suitable growth areas would decrease by 14.14% under SSP1-2.6, 15.17% under SSP2-4.5, and 19.35% under SSP5-8.5. The results revealed the impact of climate change on larch growth suitability, which can provide a scientific basis for larch forest management.
Can proactively confessing obtain your embrace? Exploring for leader’s pro-social rule-breaking consequences based on a self-verification perspective
Authors: Wang Fan , Weng Haolin , Yang Peilin , Li Yi , Zhang Man , Das Anupam Kumar 
Published: February 2023

IntroductionThe effect of leader pro-social rule breaking on employees is a critical albeit underexplored topic within the domain of study on the consequences of pro-social rule breaking in organizations. This study attempts to make up for the gap by exploring the relationship between leader pro-social rule breaking and employee voice. Drawing on the theory of self-verification, we theorize that leaders who perform pro-social rule breaking will seek feedback from their subordinates, while employees being sought will be triggered to voice upwardly, the extent to which intensity of voice is moderated by the moral courage of employees.MethodsA total of 283 dyads data of supervisor–subordinate from Shanghai, China, in a three-wave time-lagged survey provided support for our hypotheses.ResultsThe results show that leader pro-social rule breaking is positively related to leader feedback-seeking, which is positively related to employee upward voice and mediates the relationship between the two. Moreover, the positive relationship between leader pro-social rule breaking and leader feedback-seeking as well as the indirect effect of leader pro-social rule breaking on employee upward voice via leader feedback-seeking was weakened when moral courage is high.DiscussionThe present study promotes the theoretical research on the positive results of leader pro-social rule breaking and also suggests that feedback-seeking would be an effective way for leaders to motivate employees’ upward voice.