bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preliminary verification of the anti-hypoxia mechanism of Gentiana straminea maxim based on UPLC-triple TOF MS/MS and network pharmacology
Authors: Kong Xiu mei , Song Dan , Li Jie , Jiang Yi , Zhang Xiao ying , Wu Xiao Jun , Ge Ming juan , Xu Jiao jiao , Gao Xiao min , Zhao Qin 
Published: November 2022

AbstractBackgroundAnoxia is characterized by changes in the morphology, metabolism, and function of tissues and organs due to insufficient oxygen supply or oxygen dysfunction.Gentiana stramineaMaxim (G.s Maxim) is a traditional Tibetan medicine. Our previous work found that G.s Maxim mediates resistance to hypoxia, and we found that the ethyl acetate extract had the best effect. Nevertheless, the primary anti-hypoxia components and mechanisms of action remain unclear.MethodsCompounds from the ethyl acetate extraction of G.s Maxim were identified using UPLC-Triple TOF MS/MS. Then Traditional Chinese Medicine Systematic Pharmacology Database was used to filtrate them. Network pharmacology was used to forecast the mechanisms of these compounds. Male specific pathogen-free Sprague Dawley rats were randomly divided into six groups: (1) Control; (2) Model; (3) 228 mg/kg body weight Rhodiola capsules; (4) 6.66 g/kg body weight the G.s Maxim’s ethyl acetate extraction; (5) 3.33 g/kg body weight the G.s Maxim’s ethyl acetate extraction; (6) 1.67 g/kg body weight the G.s Maxim’s ethyl acetate extraction. After administering intragastric ally for 15 consecutive days, an anoxia model was established using a hypobaric oxygen chamber (7000 m, 24 h). Then Histology, enzyme-linked immunosorbent assays, and western blots were performed to determine these compounds’ anti-hypoxic effects and mechanisms. Finally, we performed a molecular docking test to test these compounds using Auto Dock.ResultsEight drug-like compounds in G.s Maxim were confirmed using UPLC-Triple TOF MS/MS and Lipinski’s rule. The tumor necrosis factor (TNF) signaling pathway, the hypoxia-inducible factor 1 (HIF-1) signaling pathway, and the nuclear factor kappa-B (NF-κB) signaling pathway was signaling pathways that G.s Maxim mediated anti-anoxia effects. The critical targets were TNF, Jun proto-oncogene (JUN), tumor protein p53 (TP53), and threonine kinase 1 (AKT1). Animal experiments showed that the ethyl acetate extraction of G.s Maxim ameliorated the hypoxia-induced damage of hippocampal nerve cells in the CA1 region and reversed elevated serum expression of TNF-α, IL-6, and NF-κ B in hypoxic rats. The compound also reduced the expression of HIF-1α and p65 and increased the Bcl-2/Bax ratio in brain tissue. These findings suggest that G.s Maxim significantly protects against brain tissue damage in hypoxic rats by suppressing hypoxia-induced apoptosis and inflammation. Ccorosolic acid, oleanolic acid, and ursolic acid had a strong affinity with core targets.ConclusionsThe ethyl acetate extraction of G.s Maxim mediates anti-hypoxic effects, possibly related to inhibiting apoptosis and inflammatory responses through the HIF-1/NF-κB pathway. The primary active components might be corosolic, oleanolic, and ursolic acids.
Healthcare cost consciousness among physicians and their attitudes towards controlling costs in Jordan: a cross sectional study
Authors: Yasin Mohmmed Hasan , Naser Abdallah Y. 
Published: November 2022

Abstract
Background
One of the most significant factors influencing medication adherence and, ultimately, therapeutic outcomes for patients is the cost. The aim of this study was to examine the cost-containment strategies used by physicians in Jordan while focusing on the importance of cost consciousness in addressing healthcare costs and its consequences.

Method
A quantitative study was conducted between June 19 and November 15, 2021, through a cross-sectional survey using a self-administered questionnaire.

Results
A total of 389 physicians participated in this study. Governments (65.6%), health insurance companies (60.2%), and pharmaceutical and device manufacturers (57.9%) were the most frequently mentioned entities as being primarily responsible for reducing healthcare costs. Participating physicians showed a high level of enthusiasm towards all domains of reducing healthcare costs with a mean percentage of 88.3% (standard deviation (SD): 0.04). When discussing physicians’ roles in containing healthcare costs and the effects of cost-conscious practice, most respondents agreed that there is currently too much emphasis on test and procedure costs (83.0%), that decision support tools that show costs would be helpful in their practice (84.5%), and that physicians need to take a more prominent role in limiting the use of unnecessary tests (86.0%). Around 70.0% of physicians agreed that they requested more tests when they did not know the patient well, and 80.0% of them stated that they considered the uncertainty involved in patient care to be disconcerting.

Conclusion
Participating physicians showed a moderate level of cost consciousness in Jordan. However, this must be higher because it will eventually lead to cost-related nonadherence, which will have a negative impact on the patient’s health.
Prevalence and trend of smokeless tobacco use and its associated factors among adolescents aged 12–16 years in 138 countries/territories, 1999–2019
Authors: Yang Hui , Ma Chuanwei , Zhao Min , Magnussen Costan G. , Xi Bo 
Published: November 2022

Abstract
Background
Smokeless tobacco use is popular in some regions worldwide, but it receives less attention compared to cigarette smoking. We aimed to estimate the recent prevalence of, and trends in, smokeless tobacco use and to examine its associated factors among adolescents aged 12–16 years in 138 countries/territories (hereafter “countries”) from 1999 to 2019.

Methods
Data from the Global Youth Tobacco Survey conducted in 138 countries in 2010–2019 and the National Youth Tobacco Survey conducted in the United States in 2019 were used to calculate the prevalence of current smokeless tobacco use and investigate its associated factors among adolescents aged 12–16 years. We also assessed the trend in the prevalence of smokeless tobacco use in 100 countries that had conducted more than one survey from 1999 to 2019.

Results
The overall prevalence of current smokeless tobacco use was 4.4% (95% confidence interval [CI] 4.0–4.9), with 5.7% (5.1–6.3) for boys, 3.1% (2.6–3.5) for girls, 3.9% (3.5–4.4) for adolescents aged 12–14 years and 5.4% (4.8–5.9) for those aged 15–16 years. The prevalence was highest in the South-East Asian region (6.1%, 4.4–7.7) and lowest in the Western Pacific region (2.0%, 1.7–2.4). The prevalence of smokeless tobacco use decreased in 57 of 100 countries, increased in 32 countries, and remained unchanged in 11 countries. Current cigarette smoking (odds ratio [OR]=2.00, 95% CI=1.68–2.39), other tobacco product use (OR=6.03, 95% CI=4.92–7.40), tobacco advertisement exposure (OR=1.44, 95% CI=1.19–1.74), being offered free tobacco products (OR=2.01, 95% CI=1.66–2.42), and not being taught about dangers of smoking (OR=1.28, 95% CI=1.09–1.50) were all positively associated with current smokeless tobacco use.

Conclusions
Smokeless tobacco use among adolescents remains a public health concern worldwide. Although the prevalence among adolescents decreased in most countries, it remains high especially in the South-East Asian region. More strict and effective strategies and measures are needed to further curb the smokeless tobacco use among adolescents.
Understanding lifestyle self-management regimens that improve the life quality of people living with multiple sclerosis: a systematic review and meta-analysis
Authors: Wills Olivia C. , Probst Yasmine C. 
Published: November 2022

Abstract
Background
Lifestyle self-management as an intervention for people living with multiple sclerosis (plwMS) is an emerging area of research. Previous reviews have highlighted a need to systematically identify effective self-management regimens that influence the health and well-being of plwMS using a common metric of success.

Objectives
To examine the effectiveness of lifestyle self-management strategies and interventions aimed at improving the quality of life (QOL), and/or disability of plwMS. The review also aimed to narratively explore common elements of self-management interventions that were effective at improving the outcomes of interest.

Methods
A systematic search was performed using five scientific databases. The review process followed the Cochrane Handbook for Systematic Reviews of Interventions and was registered with PROSPERO (Ref: CRD42021235982).

Results
A total of 57 studies including 5830 individuals diagnosed with MS, met the inclusion criteria. Self-management interventions included physical activity, fatigue, dietary, stress/coping, emotional, symptom and medical management, and lifestyle and wellbeing programs. Self-reported QOL improved in 35 of 47 studies. Dietary intervention had no statistically significant overall effect on reducing MS disability, (P = 0.18). Heterogeneity limited the ability to pool the effects from a large number of eligible studies of the same design.

Conclusion
Multicomponent self-management interventions, multimodal delivery methods, and cognitive behavioural theory principles were common elements of self-management interventions that improved the QOL of plwMS. However, these results should be interpreted with caution and care should be taken in its clinical application. This review has the potential to inform future management practices for plwMS and has revealed a significant gap in the literature, warranting high-quality, large-scale experimental, and observational studies that address lifestyle management.
Chinese cross-culturally adapted patient-reported outcome measures (PROMs) for knee disorders: a systematic review and assessment using the Evaluating the Measurement of Patient-Reported Outcomes (EMPRO) instrument
Authors: Ngwayi James Reeves Mbori , Obie Kenedy Uzoma , Tan Jie , Xu JianBiao , Alizada Mujahid , Porter Daniel Edward 
Published: November 2022

Abstract
Background
Knee patient-reported outcome measures (PROMs) are widely used in research in China, but there is limited evidence on the quality of cross-culturally adapted and original Chinese PROMs. We investigated Chinese language knee PROMs to provide evidence for clinicians on their quality and to guide PROM choices.

Method
A systematic literature search of databases: PUBMED, CINAHL, EMBASE, and CNKI, using adequate search strings and a three-step screen process identified relevant studies. An independent standardized assessment of the selected studies based on the Evaluating the Measurement of Patient-Reported Outcomes (EMPRO) tool was performed. Inter-rater reliability was assessed using intraclass coefficients (ICC).

Results
Thirty-three articles corresponding to 23 knee PROMs were evaluated with EMPRO global scores (100) ranging from 11.11 to 55.42. The attributes ‘reliability,’ ‘validity,’ and ‘cultural and language adaptation’ were significantly better evaluated compared to the attributes ‘responsiveness,’ ‘interpretability,’ and ‘burden’ (for all comparisons p < 0.0001). Moderate-to-excellent inter-rater agreement was observed with ICC values ranging from 0.538 to 0.934.

Conclusion
We identified six PROMs with a minimum acceptable threshold (> 50/100). The osteoarthritis of knee and hip quality of life, the lower extremity function scale, and the Western Ontario Meniscal Evaluation tool ranked highest. Nevertheless, no single PROM had evidence encompassing all EMPRO attributes, necessitating further studies, especially on responsiveness, interpretability, and burden. We identified duplication of effort as shown by repeated translations of the same PROM; this inefficiency could be ameliorated by rapid approval of Chinese language PROMs documented on original PROM developers’ platforms.
Identification of potential immunomodulators from Pulsatilla decoction that act on therapeutic targets for ulcerative colitis based on pharmacological activity, absorbed ingredients, and in-silico molecular docking
Authors: Deng Li-rong , Han Qian , Zou Min , Chen Fang-jun , Huang Chang-yin , Zhong Yi-ming , Wu Qian-yan , Tomlinson Brian , Li Yan-hong 
Published: November 2022

Abstract
Background
Pulsatilla decoction (Bai-Tou-Weng-Tang, BTWT) is a classic formula prescription of a traditional Chinese medicine that is used to treat ulcerative colitis (UC). However, its active components and underlying mechanism of action remain unclear. In the present study, we aimed to identify potential immunomodulators from BTWT that act at therapeutic targets for UC.

Methods
The protective effects of BTWT granules were examined in mice with colitis induced by dextran sulfate sodium. The absorbed components of BTWT were identified using LC-MS, and selected protein targets of these components in UC were investigated using molecular docking.

Results
Oral administration of BTWT granules significantly alleviated disease severity and colon shortening, and inhibited the inflammatory response in mice with chronic colitis. In these mice, 11 compounds from the BTWT granules were detected in the serum and/or colon. The molecular docking study demonstrated that compounds from Radix pulsatillae, such as anemoside A3, interacted with STAT3 and S1PR1; compounds from Rhizoma coptidis and/or Cortex phellodendri, such as palmatine, interacted with JAK3, PD-1, and PD-L1; and components of Cortex fraxini such as aesculin interacted with S1PR1, JAK3, STAT3 and PD-L1. Further in-vitro experiments showing that the compounds inhibited TNF-α and IL-6 production and STAT3 activation in RAW 264.7 cells suggested that these compounds have immunomodulatory activities.

Conclusion
We revealed for the first time that 11 absorbed ingredients from BTWT were immunomodulators against therapeutic targets for UC. These findings suggest that the identified compounds are the active components of BTWT, and the identified protein targets underlie the mechanism of action of BTWT against UC.
Feasibility, effectiveness and costs of a decision support intervention for consultees and legal representatives of adults lacking capacity to consent (CONSULT): protocol for a randomised Study Within a Trial
Authors: Shepherd Victoria , Wood Fiona , Gillies Katie , Martin Adam , O’Connell Abby , Hood Kerenza 
Published: November 2022

Abstract
Background
Randomised trials play a vital role in underpinning evidence-based care. However, trials involving adults with impaired capacity to consent raise a number of ethical and methodological challenges, leading to the frequent exclusion of this group from trials. This includes challenges around involving family members as alternative ‘proxy’ decision-makers. Family members are often given little information about their role as a consultee or legal representative. Some family members find making a decision about trial participation difficult and may experience an emotional and decisional burden as a result. Families have reported a need for greater support and guidance when making such decisions, leading to the development of a decision aid (‘Making decisions about research for others’) for family members acting as consultee/legal representative. The decision aid now requires evaluation to determine its effectiveness in supporting families to make more informed decisions.

Methods
This protocol describes a prospective, multi-centre, randomised-controlled Study Within a Trial (SWAT) to evaluate the effectiveness of the decision aid. The SWAT will initially be embedded in approximately five host trials. SWAT participants will be randomised in a 1:1 ratio to either the intervention (decision aid alongside standard information about the host trial provided to consultees/legal representatives) or control (standard information alone). The primary outcome is the quality of proxy consent decision, assessed by the Combined Scale for Proxy Informed Consent Decisions (CONCORD). The SWAT design is informed by previous qualitative research. Initial feasibility will be explored in one host trial, followed by the main SWAT. An embedded process evaluation and economic evaluation will enable the SWAT findings to be contextualised and identify factors likely to affect implementation.

Discussion
This SWAT will generate the first evidence for recruitment interventions for trials involving adults lacking capacity to consent and add to knowledge about the use of decision support interventions in trial participation decisions. The SWAT will be embedded in a range of trials, and the heterogenous nature of the host trials, settings and populations involved will enable the intervention to be evaluated in a wide range of contexts. However, a pragmatic and flexible approach to conducting the SWAT is needed.

Trial registration
The SWAT is registered as SWAT #159 with the Northern Ireland Hub for Trials Methodology Research SWAT repository (registered 09.08.2020). Each host trial will be registered on a clinical trials registry.
Synthesis of nanosize zinc oxide through aqueous sol–gel route in polyol medium
Authors: Zahra Samreen , Bukhari Hamim , Qaisar Saboora , Sheikh Asma , Amin Athar 
Published: November 2022

Abstract
Background
This study is aimed to synthesize nanosize zinc oxide by acid catalyzed sol–gel process using zinc nitrate hexahydrate as precursor, aqueous isopropanol as solvent and glycerin for making polyol system. The polyol mediated procedure was employed in combination with calcination induced synthesis of nanoparticles of numerous sizes obtained with the variation in calcination temperature from 500 to 900 ℃. The crystal structure of the prepared samples was characterized by X-ray diffraction analysis (XRD). Infrared spectroscopy (IR) was used to identify the surface hydroxyl groups. Thermal stability was confirmed by differential scanning calorimetry-thermogravimetric analysis (DSC-TGA) whereas field emission scanning electron microscopy (FESEM) was used to study the surface morphology of nanoparticles.

Results
Results revealed the formation of hexagonal wurtzite structure of irregular shaped nanoparticles having size ranging from 50–100 nm. However, the particles combined to form agglomerates of 200–400 nm with the rise in calcination temperature.

Conclusions
These results indicate that nanosize zinc oxide can be synthesized successfully by a simple process comprising of glycerin as a low-cost, non-toxic and eco-friendly polyol followed by calcination at ambient temperatures.
Synthesis, in silico studies and biological screening of (E)-2-(3-(substitutedstyryl)-5-(substitutedphenyl)-4,5-dihydropyrazol-1-yl)benzo[d]thiazole derivatives as an anti-oxidant, anti-inflammatory and antimicrobial agents
Authors: Kumar Manoj , Kumar Vijay , Singh Vikramjeet , Thakral Samridhi 
Published: November 2022

AbstractA new series of (E)-2-(3-(substitutedstyryl)-5-(substitutedphenyl)-4,5-dihydropyrazol-1-yl)benzo[d]thiazole derivatives was synthesized and the chemical structures of synthesized compounds were deduced by IR and NMR spectral tools. These compounds were synthesized via aldol condensation reaction of substituted benzaldehydes and acetone in alkaline ethanolic solution and their in vitro anti-oxidant, anti-inflammatory and antimicrobial activities were investigated. All the synthesized compounds displayed anti-oxidant potential with IC50values ranging from 0.13 to 8.43 µmol/ml. The compoundZ13exhibited potent anti-inflammatory activity with IC50value of 0.03 µmol/ml compared with the standard ibuprofen, which showed IC50value of 0.11 µmol/ml. On the other hand, most of the compounds had a certain antibacterial potential particularly againstP. aeruginosaand among these derivatives, compoundZ2exhibited the highest potential againstP. aeruginosawith MIC value of 0.0069 µmol/ml. The analysis of docking results demonstrated the binding affinity and hydrogen bond, electrostatic and hydrophobic interactions of all the synthesized compounds with their respective targets. In silico ADMET studies were carried out for the synthesized compounds and most of the compounds exhibited good ADMET profile.
Economic impact of self-administered subcutaneous versus clinic-administered intravenous immunoglobulin G therapy in Alberta, Canada: a population-based cohort study
Authors: Ritchie Bruce , Martins Karen J. B. , Tran Dat T. , Blain Heather , Richer Lawrence , Klarenbach Scott W. 
Published: November 2022

Abstract
Background
Self-administered subcutaneous immunoglobulin G (SCIg) reduces nursing time and eliminates the need for treatment at ambulatory care clinics, as compared with clinic-based intravenously administered IgG (IVIg), and are therapeutically equivalent. Estimating the economic impact of self-administered SCIg versus clinic-administered IVIg therapy may guide treatment recommendations.

Methods
A retrospective population-based cohort study using administrative data from Alberta was performed; those treated with IgG between April 1, 2012 and March 31, 2019 were included. Costs for medical laboratory staff and nursing time, as well as ambulatory care visits were considered. Univariate generalized linear model regression with gamma distribution and log link was used to compare cost ($CDN 2020) between SCIg and IVIg administration. Stratified analysis by age (≥ 18-years; < 18-years) was performed.

Results
Among 7,890 (6,148 adults; 1,742 children) individuals who received IgG, the average administration cost per patient-year of self-administered SCIg was $5,386 (95% confidence interval [CI] $5,039, $5,734) lower than clinic-administered IVIg; per patient-year cost of self-administered SCIg was $817 (95% CI $723, $912) versus $6,204 (95% CI $6,100, $6,308) for clinic-administered IVIg. The per patient-year cost of self-administered SCIg was $5,931 (95% CI $5,543, $6,319) lower among adults and $3,177 (95% CI $2,473, $3,882) lower among children compared with clinic-administered IVIg. An estimated $31.0 million (95% CI $29.0, $33.0) in cost savings to the health system would be realised if 80% of individuals switched from clinic-administered IVIg to self-administered SCIg.

Conclusions
Self-administered SCIg is substantially less costly from a health care payer perspective in Canada. Within this type of health system, switching to self-administered SCIg has the potential to reduce overall health care costs, lessen nursing burden, and may increase clinic-based capacity for others.