bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ethnodemographic characterization of stroke incidence and burden of disease in hospital discharge records in Ecuador
Authors: Carrington Sarah J. , Romero-Alvarez Daniel , Coral-Almeida Marco , Vela Andrea , Henríquez-Trujillo Aquiles Rodrigo , Mascialino Guido 
Published: February 2023

IntroductionStroke is the second most common cause of death and disability-adjusted life years (DALYs) globally. However, the incidence and impact of stroke by ethnicity and gender is frequently distinct. This is particularly the case in Ecuador where geographic and economic marginalization are often correlated with ethnic marginalization and the extent to which females lack the same opportunities as their male counterparts. The aim of this paper is to investigate the differential impacts in terms of stroke diagnosis and burden of disease by ethnicity and gender, using hospital discharge records over the years 2015–2020.MethodsThis paper calculates stroke incidence, and fatality rates using hospital discharge and death records over the years 2015–2020. The DALY package in R was employed to calculate the Disability Adjusted Life Years lost due to stroke in Ecuador.ResultsThe results show that while the incidence rate of stroke in males (64.96 per 100,000 persons-year) is higher than that for females on average (57.84 per 100,000 persons-year), males accounted for 52.41% of all stroke cases and 53% of all surviving cases. Thus, hospital data suggests that females had a higher death rate when compared to males. Case fatality rates also differed significantly by ethnicity. The highest fatality rate corresponded to the Montubio ethnic group (87.65%), followed by Afrodescendants (67.21%). The estimated burden of disease of stroke calculated using Ecuadorian hospital records (2015–2020) varied from 1,468 to 2,991 DALY per 1,000 population on average.DiscussionDifferences in the burden of disease by ethnic group are likely to reflect differential access to care by region and socio-economic group, both of which are frequently correlated with ethnic composition in Ecuador. Equitable access to health services remains an important challenge in the country. The gender discrepancy in fatality rates suggests that there is a need for targeted educational campaigns to identify stroke signs early, especially in the female population.
Combination of platelet-to-lymphocyte ratio and D-dimer for the identification of cardiogenic cerebral embolism in non-valvular atrial fibrillation
Authors: Shi Yachen , Xuan Chenhao , Ji Wei , Wang Feng , Huang Jin , Li Lei , Wang Hui , Deng Jingyu , Shao Junfei , Chen Kefei , Mao Xuqiang , Xu Qinghua , You Yiping , Xi Guangjun 
Published: February 2023

BackgroundNon-valvular atrial fibrillation (NVAF) is the most common cause of cardiogenic cerebral embolism (CCE). However, the underlying mechanism between cerebral embolism and NVAF is indefinite, and there is no effective and convenient biomarker to identify potential risk of CCE in patients with NVAF in clinic. The present study aims to identify risk factors for interpreting the potential association of CCE with NVAF and providing valuable biomarkers to predict the risk of CCE for NVAF patients.Methods641 NVAF patients diagnosed with CCE and 284 NVAF patients without any history of stroke were recruited in the present study. Clinical data including demographic characteristics, medical history, and clinical assessments, were recorded. Meanwhile, Blood cell counts, lipid profiles, high-sensitivity C-reactive protein, and coagulation function-related indicators were measured. Least absolute shrinkage and selection operator (LASSO) regression analysis was utilized to build a composite indicator model based on the blood risk factors.Results(1) CCE patients had significantly increased neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), and D-dimer levels as compared with patients in the NVAF group, and these three indicators can distinguish CCE patients from ones in the NVAF group with an area under the curve (AUC) value of over 0.750, respectively. (2) Using the LASSO model, a composite indicator, i.e., the risk score, was determined based on PLR and D-dimer and displayed differential power for distinguishing CCE patients from NVAF patients with an AUC value of over 0.934. (3) The risk score was positively correlated with the National Institutes of Health Stroke Scale and CHADS2 scores in CCE patients. (4) There was a significant association between the change value of the risk score and the recurrence time of stroke in initial CCE patients.ConclusionsThe PLR and D-dimer represent an aggravated process of inflammation and thrombosis in the occurrence of CCE after NVAF. The combination of these two risk factors can contribute to identifying the risk of CCE for patients with NVAF with an accuracy of 93.4%, and the greater in change of composite indicator, the shorter in the recurrence of CCE for NVAF patients.
Neuropathic pain experience in symptomatic and presymptomatic subjects carrying a transthyretin gene mutation
Authors: Tozza Stefano , Luigetti Marco , Antonini Giovanni , Mazzeo Anna , Severi Daniele , Di Paolantonio Andrea , Leonardi Luca , Russo Massimo , Romano Angela , Forcina Francesca , Gentile Luca , Nolano Maria , Mattia Consalvo , Manganelli Fiore 
Published: February 2023

IntroductionPain is a common symptom of hereditary transthyretin amyloidosis (ATTRv), however, its occurrence in late-onset ATTRv has not been investigated thoroughly. Our aim was to describe the pain experience and its impact on quality of life (QoL) in symptomatic patients and presymptomatic carriers harboring a transthyretin (TTR) gene mutation with a late-onset phenotype.Materials and methodsStudy participants (aged ≥18 years) were consecutively recruited from four Italian centers. Clinical disability was assessed using the Familial Amyloid Polyneuropathy (FAP) stage and Neuropathy Impairment Score (NIS). The Norfolk questionnaire evaluated QoL and the Compound Autonomic Dysfunction Test assessed autonomic involvement. Neuropathic pain was screened using the Douleur Neuropathique 4 (DN4) questionnaire, and pain intensity and its impact on daily activity were assessed using the Brief Pain Inventory severity and interference subscores. Data on the type of TTR mutation, presence of cardiomyopathy, treatment, and Body Mass Index (BMI) were collected.ResultsOverall, 102 subjects with TTR mutations (mean age ± SD 63.6 ± 13.5 years) were recruited, including 78 symptomatic patients (68.1 ± 10.9 years) and 24 presymptomatic carriers (49 ± 10.3 years). Pain was reported by 75.5% of all subjects, but was more frequent in symptomatic patients than in presymptomatic carriers (85.9 vs. 41.6%, respectively). Pain exhibited neuropathic features (DN4≥4) in 69.2% of symptomatic patients and in 8.3% of presymptomatic carriers. Subjects with neuropathic pain were older (p = 0.015) had worse FAP stage (p &lt; 0.001), higher NIS scores (p &lt; 0.001), greater autonomic involvement (p = 0.003), and a lower QoL (p &lt; 0.001) than those without neuropathic pain. Neuropathic pain was associated with higher pain severity (p &lt; 0.001) and had a significant negative impact on daily activities (p &lt; 0.001) Neuropathic pain was not associated with gender, mutation type, TTR therapy, or BMI.ConclusionApproximately 70% of late-onset ATTRv patients complained of neuropathic pain (DN4≥4) that worsened as peripheral neuropathy progressed and increasingly interfered with daily activities and QoL. Notably, 8% of presymptomatic carriers complained of neuropathic pain. These results suggest that assessment of neuropathic pain may be useful to monitor disease progression and identify early manifestations of ATTRv.
Effects of traditional Chinese medicine combined with modern rehabilitation therapies on motor function in children with cerebral palsy: A systematic review and meta-analysis
Authors: Chen Zhengquan , Huang Zefan , Li Xin , Deng Weiwei , Gao Miao , Jin Mengdie , Zhou Xuan , Du Qing 
Published: February 2023

ObjectiveTraditional Chinese Medicine (TCM) has considerable experience in the treatment of cerebral palsy (CP), but little evidence shows the effect of a combination of TCM and modern rehabilitation therapies on CP. This systematic review aims to evaluate the effect of integrated TCM and modern rehabilitation therapies on motor development in children with CP.MethodsWe systematically searched five databases up to June 2022, including PubMed, the Cumulative Index to Nursing and Allied Health, Cochrane Library, Embase, and Web of Science. Gross motor function measure (GMFM) and Peabody Development Motor Scales-II were the primary outcomes to evaluate motor development. Secondary outcomes included the joint range of motion, the Modified Ashworth scale (MAS), the Berg balance scale, and Activities of Daily living (ADL). Weighted mean differences (WMD) and 95% confidence intervals (CIs) were used to determine intergroup differences.ResultsA total of 2,211 participants from 22 trials were enrolled in this study. Among these, one study was at a low risk of bias and seven studies showed a high risk of bias. Significant improvements were found in GMFM-66 (WMD 9.33; 95% CI 0.14–18.52, P &lt; 0.05, I2 = 92.1%), GMFM-88 (WMD 8.24; 95% CI 3.25–13.24, P &lt; 0.01, I2 = 0.0%), Berg balance scale (WMD 4.42; 95% CI 1.21–7.63, P &lt; 0.01, I2 = 96.7%), and ADL (WMD 3.78; 95% CI 2.12–5.43, P &lt; 0.01, I2 = 58.8%). No adverse events were reported during the TCM intervention in the included studies. The quality of evidence was high to low.ConclusionIntegrated TCM and modern rehabilitation therapies may be an effective and safe intervention protocol to improve gross motor function, muscle tone, and the functional independence of children with CP. However, our results should be interpreted carefully because of the heterogeneity between the included studies.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022345470.
Spatiotemporal profile of altered neural reactivity to food images in obesity: Reward system is altered automatically and predicts efficacy of weight loss intervention
Authors: Poghosyan Vahe , Ioannou Stephanos , Al-Amri Khalid M. , Al-Mashhadi Sufana A. , Al-Mohammed Fedaa , Al-Otaibi Tahani , Al-Saeed Wjoud 
Published: February 2023

IntroductionObesity presents a significant public health problem. Brain plays a central role in etiology and maintenance of obesity. Prior neuroimaging studies have found that individuals with obesity exhibit altered neural responses to images of food within the brain reward system and related brain networks. However, little is known about the dynamics of these neural responses or their relationship to later weight change. In particular, it is unknown if in obesity, the altered reward response to food images emerges early and automatically, or later, in the controlled stage of processing. It also remains unclear if the pretreatment reward system reactivity to food images is predictive of subsequent weight loss intervention outcome.MethodsIn this study, we presented high-calorie and low-calorie food, and nonfood images to individuals with obesity, who were then prescribed lifestyle changes, and matched normal-weight controls, and examined neural reactivity using magnetoencephalography (MEG). We performed whole-brain analysis to explore and characterize large-scale dynamics of brain systems affected in obesity, and tested two specific hypotheses: (1) in obese individuals, the altered reward system reactivity to food images occurs early and automatically, and (2) pretreatment reward system reactivity predicts the outcome of lifestyle weight loss intervention, with reduced activity associated with successful weight loss.ResultsWe identified a distributed set of brain regions and their precise temporal dynamics that showed altered response patterns in obesity. Specifically, we found reduced neural reactivity to food images in brain networks of reward and cognitive control, and elevated reactivity in regions of attentional control and visual processing. The hypoactivity in reward system emerged early, in the automatic stage of processing (&lt; 150 ms post-stimulus). Reduced reward and attention responsivity, and elevated neural cognitive control were predictive of weight loss after six months in treatment.DiscussionIn summary, we have identified, for the first time with high temporal resolution, the large-scale dynamics of brain reactivity to food images in obese versus normal-weight individuals, and have confirmed both our hypotheses. These findings have important implications for our understanding of neurocognition and eating behavior in obesity, and can facilitate development of novel integrated treatment strategies, including tailored cognitive-behavioral and pharmacological therapies.
The association of vitamin D status with oxidative stress biomarkers and matrix metalloproteinases in patients with knee osteoarthritis
Authors: Amirkhizi Farshad , Ghoreishy Seyed Mojtaba , Baker Emma , Hamedi-Shahraki Soudabeh , Asghari Somayyeh 
Published: February 2023

ObjectiveThe association of vitamin D status with osteoarthritis (OA) has been demonstrated previously. The current study was performed to examine the association of vitamin D status with oxidative stress markers and matrix metalloproteinases (MMPs) in patients with knee OA.MethodsThis case–control study was conducted on 124 subjects with mild to moderate knee OA and 65 healthy controls. Demographic data was collected from all participants at baseline. Serum levels of vitamin D as well as markers of oxidative stress including malondialdehyde (MDA), total oxidant status (TOS), superoxide dismutase (SOD), oxidative stress index (OSI), paraoxonase-1 (PON-1), glutathione peroxidase (GPX), catalase (CAT), and total antioxidant capacity (TAC) were evaluated for each participant. Furthermore, serum concentrations of MMP-1, MMP-3, MMP-13, and cartilage oligomeric matrix protein (COMP) were measured.ResultsThe results of the present study indicated that individuals with vitamin D insufficiency had higher levels of MDA, TOS, SOD, and OSI as well as lower levels of PON-1 and TAC. Based on the linear regression analysis, serum vitamin D levels were inversely correlated with MDA, TOS, SOD, OSI, MMP-1, and MMP-13 and positively associated with TAC levels (p &lt; 0.0001). Patients with sufficient vitamin D levels had lower MMP-1 and MMP-13 levels compared to patients with vitamin D insufficiency (p &lt; 0.001 and p &lt; 0.001, respectively).ConclusionFindings from this study showed a strong association between vitamin D deficiency and increased oxidative stress and MMPs activity in patients with knee OA.
Atractylenolide-1 Targets FLT3 to Regulate PI3K/AKT/HIF1-α Pathway to Inhibit Osteogenic Differentiation of Human Valve Interstitial Cells
Authors: Wang Jie , Zhang Penghua , Zhang Jing , Ma Zhaohui , Tian Xingqin , Liu Yan , Lv Guanghui , Qu Linghang 
Published: February 2023

Atractylenolide-1 (AT-1), a natural active ingredient extracted from Atractylodes macrocephala, was reported to have good anti-fibrotic and anti-inflammatory effects. Osteogenic changes induced by the inflammation of valve interstitial cells (VICs) play a role in the development of calcified aortic valve disease (CAVD). This study aimed to investigate the anti-osteogenic effects of AT-1 in human VICs. Human VICs were exposed to osteogenic induction medium (OM) containing AT-1 to analyze cell viability, as well as protein and osteogenic gene expression. Anti-calcification tests were also performed. mRNA transcriptome sequencing was performed to identify differential genes and pathways regulated by AT-1. Western blotting was used to verify the enrichment pathway, protein-protein interaction (PPI) analysis was conducted to identify drug targets. Finally, molecular docking and inhibitors are used to verify the drug targets. Treatment of VICs with 20 μM AT-1 resulted in no significant cytotoxicity. The addition of AT-1 to OM prevented the accumulation of calcified nodules, and decreases in the level of (Alkaline Phosphatase) ALP and RUNX2 gene and protein expression were observed. Atractylenolide-1 can target FLT3 protein and inhibit the phosphorylation of FLT3, thereby blocking PI3K/AKT pathway activation, reducing the production of Hypoxia inducible factor(HIF)1-α, and inhibiting the osteogenic differentiation of VICs. These results suggest AT-1 as a potential drug for treating calcified aortic valve disease.
Regional variations in excessive polypharmacy and potentially inappropriate drug use among older adults in Sweden: Trends from 2006 to 2020
Authors: Wastesson Jonas W. , Fritzell Johan , Burström Bo , Johnell Kristina , Fastbom Johan 
Published: February 2023

Introduction: Potentially inappropriate drug use (PID) is common among older adults. Cross-sectional data suggest that there are marked regional variations in PID in Sweden. There is, however, a lack of knowledge about how the regional variations have changed over time.Objectives: This study aimed to investigate the regional differences in the prevalence of PID in Sweden, 2006–2020.Methods: In this repeated cross-sectional study, we included all older adults (≥75 years) registered in Sweden, yearly from 2006 to 2020. We used nationwide data from the Swedish Prescribed Drug Register linked at the individual level to the Swedish Total Population Register. We selected three indicators of PID according to the Swedish national “Quality indicators for good drug therapy in the elderly”: 1) Excessive polypharmacy (use of ≥10 drugs); 2) Concurrent use of three or more psychotropic drugs; 3) Use of “drugs that should be avoided in older adults unless specific reasons exist.” The prevalence of these indicators was calculated for each of Sweden’s 21 regions, yearly from 2006 to 2020. The annual coefficient of variation (CV) was calculated for each indicator by dividing the standard deviation of the regions by the national average, to measure relative variability.Results: In the population of about 800,000 older adults per year, the national prevalence of “drugs that should be avoided in older adults,” was reduced by 59% from 2006 to 2020. There was a slight decline in the use of three or more psychotropics, while the prevalence of excessive polypharmacy increased. The CV for excessive polypharmacy was 14% in 2006 and 9% in 2020 compared to 18% and 14% for “use of three or more psychotropics”, and stable at around 10% for ‘drugs that should be avoided in older adults.’Conclusions: The regional variation in potentially inappropriate drug use decreased or were stable from 2006 to 2020. The regional differences were largest for the use of three or more psychotropics. We found a general tendency that regions with a good performance at the start of the period performed well across the entire period. Future studies should investigate the reasons for regional variation and explore strategies to reduce unwarranted differences.
Development of a microphysiological skin-liver-thyroid Chip3 model and its application to evaluate the effects on thyroid hormones of topically applied cosmetic ingredients under consumer-relevant conditions
Authors: Tao Thi-Phuong , Maschmeyer Ilka , LeCluyse Edward L. , Rogers Eda , Brandmair Katrin , Gerlach Silke , Przibilla Julia , Kern Fredy , Genies Camille , Jacques Carine , Najjar Abdulkarim , Schepky Andreas , Marx Uwe , Kühnl Jochen , Hewitt Nicola J. 
Published: February 2023

All cosmetic ingredients registered in Europe must be evaluated for their safety using non-animal methods. Microphysiological systems (MPS) offer a more complex higher tier model to evaluate chemicals. Having established a skin and liver HUMIMIC Chip2 model demonstrating how dosing scenarios impact the kinetics of chemicals, we investigated whether thyroid follicles could be incorporated to evaluate the potential of topically applied chemicals to cause endocrine disruption. This combination of models in the HUMIMIC Chip3 is new; therefore, we describe here how it was optimized using two chemicals known to inhibit thyroid production, daidzein and genistein. The MPS was comprised of Phenion® Full Thickness skin, liver spheroids and thyroid follicles co-cultured in the TissUse HUMIMIC Chip3. Endocrine disruption effects were determined according to changes in thyroid hormones, thyroxine (T4) and 3,3’,5-triiodothyronine (T3). A main part of the Chip3 model optimization was the replacement of freshly isolated thyroid follicles with thyrocyte-derived follicles. These were used in static incubations to demonstrate the inhibition of T4 and T3 production by genistein and daidzein over 4 days. Daidzein exhibited a lower inhibitory activity than genistein and both inhibitory activities were decreased after a 24 h preincubation with liver spheroids, indicating metabolism was via detoxification pathways. The skin-liver-thyroid Chip3 model was used to determine a consumer-relevant exposure to daidzein present in a body lotion based on thyroid effects. A “safe dose” of 0.235 μg/cm2 i.e., 0.047% applied in 0.5 mg/cm2 of body lotion was the highest concentration of daidzein which does not result in changes in T3 and T4 levels. This concentration correlated well with the value considered safe by regulators. In conclusion, the Chip3 model enabled the incorporation of the relevant exposure route (dermal), metabolism in the skin and liver, and the bioactivity endpoint (assessment of hormonal balance i.e., thyroid effects) into a single model. These conditions are closer to those in vivo than 2D cell/tissue assays lacking metabolic function. Importantly, it also allowed the assessment of repeated doses of chemical and a direct comparison of systemic and tissue concentrations with toxicodynamic effects over time, which is more realistic and relevant for safety assessment.
Bu-Fei-Huo-Xue capsule alleviates bleomycin-induced pulmonary fibrosis in mice through modulating gut microbiota
Authors: Hu Haibo , Wang Fengchan , Han Ping , Li Peng , Wang Kun , Song Huan , Zhao Guojing , Li Yue , Lu Xuechao , Tao Weihong , Cui Huantian 
Published: February 2023

Introduction: Bu-Fei-Huo-Xue capsule (BFHX) has been used to treat pulmonary fibrosis (PF) in clinic. However, the mechanism of Bu-Fei-Huo-Xue capsule on pulmonary fibrosis remains unclear. Recent studies have shown that the changes in gut microbiota were closely related to the progression of pulmonary fibrosis. Modulating gut microbiota provides new thoughts in the treatment of pulmonary fibrosis.Methods: In this study,a mouse model of pulmonary fibrosis was induced using bleomycin (BLM) and treated with Bu-Fei-Huo-Xue capsule. We firstly evaluated the therapeutic effects of Bu-Fei-Huo-Xue capsule on pulmonary fibrosis model mice. Besides,the anti-inflammatory and anti- oxidative effects of Bu-Fei-Huo-Xue capsule were evaluated. Furthermore, 16S rRNA sequencing was used to observe the changes in gut microbiota in pulmonary fibrosis model mice after Bu-Fei-Huo-Xue capsule treatment.Results: Our results showed that Bu-Fei-Huo-Xue capsule significantly reduced the collagen deposition in pulmonary fibrosis model mice. Bu-Fei-Huo-Xue capsule treatment also reduced the levels and mRNA expression of pro-inflammatory cytokines and inhibited the oxidative stress in lung. 16S rRNA sequencing showed that Bu-Fei-Huo-Xue capsule affected the diversity of gut microbiota and the relative abundances of gut microbiota such as Lactobacillus, Lachnospiraceae_NK4A136_group, and Romboutsia.Conclusion: Our study demonstrated the therapeutic effects of Bu-Fei-Huo-Xue capsule on pulmonary fibrosis. The mechanisms of Bu-Fei-Huo-Xue capsule on pulmonary fibrosis may be associated with regulating gut microbiota.