bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does higher health literacy lead to higher trust in public hospitals?
Authors: Bertram Maja , Brandt Urs Steiner , Hansen Rikke Klitten , Svendsen Gert Tinggaard 
Published: September 2021

Abstract
Background
Does higher health literacy lead to higher trust in public hospitals? Existing literature suggests that this is the case since a positive association between the level of health literacy and the level of trust in physicians and the health care system has been shown. This study aims to challenge this assumption.

Methods
Based on theoretical arguments from game theory and analysis of empirical data, we argue that the association is better described as an inversely u-shaped curve, suggesting that low and high levels of health literacy lead to a lower level of trust than a medium level of health literacy does. The empirical analysis is based on a study of the Danes’ relationship to the overall health care system. More than 6000 Danes have been asked about their overall expectations of the health service, their concrete experiences and their attitudes to a number of change initiatives.

Results
Game theory analysis show that the combined perceived cooperation and benefit effects can explain an inversely u-shaped relationship between social groups and trust in the health care system. Based on quantitative, binary regression analyses of empirical data, the lowest degree of trust is found among patients from the lowest and highest social groups, while the highest degree of trust is found in the middle group. The main driver for this result is that while patients having low health literacy perceive that the health care system is not cooperative, patients with a high level of health literacy have high expectations about the quality, which the health care system might not be able to provide. This reduces the perceived benefit from their encounter with the health care system.

Conclusion
It is important that health care professionals understand that some patient groups have a higher chance of cooperation (e.g., agreeing on the choice of treatment) or defection (e.g. passing a complaint) than others. In perspective, future research should undertake further qualitative examinations of possible patient types and their demands in relation to different health care sectors, focusing specifically on the opportunities to improve the handling of different patient types.
Mental and physical health, and long-term quality of life among service members injured on deployment
Authors: McCabe Cameron T. , Watrous Jessica R. , Eskridge Susan L. , Galarneau Michael R. 
Published: September 2021

Abstract
Background
More than 52,000 casualties have been documented in post-9/11 conflicts. Service members with extremity injuries (EIs) or traumatic brain injury (TBI) may be at particular risk for long-term deficits in mental and physical health functioning compared with service members with other injuries.

Methods
The present study combined medical records with patient reports of mental health and health-related quality of life (HRQOL) for 2,537 service members injured in overseas contingency operations who participated in the Wounded Warrior Recovery Project. Combined parallel-serial mediation models were tested to examine the pathways through which injury is related to mental and physical health conditions, and long-term HRQOL.

Results
Results revealed that injury was indirectly related to long-term HRQOL via its associations with physical health complications and mental health symptoms. Relative to TBI, EI was associated with a higher likelihood for a postinjury diagnosis for a musculoskeletal condition, which were related to lower levels of later posttraumatic stress disorder (PTSD) symptoms, and higher levels of physical and mental HRQOL. Similarly, EI was related to a lower likelihood for a postinjury PTSD diagnosis, and lower levels of subsequent PTSD symptoms, and therefore higher physical and mental HRQOL relative to those with TBI. Despite this, the prevalence of probable PTSD among those with EI was high (35%). Implications for intervention, rehabilitation, and future research are discussed.
Determination of a six-gene prognostic model for cervical cancer based on WGCNA combined with LASSO and Cox-PH analysis
Authors: Li Shiyan , Han Fengjuan , Qi Na , Wen Liyang , Li Jia , Feng Cong , Wang Qingling 
Published: September 2021

Abstract
Aim
This study aimed to establish a risk model of hub genes to evaluate the prognosis of patients with cervical cancer.

Methods
Based on TCGA and GTEx databases, the differentially expressed genes (DEGs) were screened and then analyzed using GO and KEGG analyses. The weighted gene co-expression network (WGCNA) was then used to perform modular analysis of DEGs. Univariate Cox regression analysis combined with LASSO and Cox-pH was used to select the prognostic genes. Then, multivariate Cox regression analysis was used to screen the hub genes. The risk model was established based on hub genes and evaluated by risk curve, survival state, Kaplan-Meier curve, and receiver operating characteristic (ROC) curve.

Results
We screened 1265 DEGs between cervical cancer and normal samples, of which 620 were downregulated and 645 were upregulated. GO and KEGG analyses revealed that most of the upregulated genes were related to the metastasis of cancer cells, while the downregulated genes mostly acted on the cell cycle. Then, WGCNA mined six modules (red, blue, green, brown, yellow, and gray), and the brown module with the most DEGs and related to multiple cancers was selected for the follow-up study. Eight genes were identified by univariate Cox regression analysis combined with the LASSO Cox-pH model. Then, six hub genes (SLC25A5, ENO1, ANLN, RIBC2, PTTG1, and MCM5) were screened by multivariate Cox regression analysis, and SLC25A5, ANLN, RIBC2, and PTTG1 could be used as independent prognostic factors. Finally, we determined that the risk model established by the six hub genes was effective and stable.

Conclusions
This study supplies the prognostic value of the risk model and the new promising targets for the cervical cancer treatment, and their biological functions need to be further explored.
Risk of heparinoid use in cosmetics and moisturizers in individuals vaccinated against severe acute respiratory syndrome coronavirus 2
Authors: Yamamoto Kenji 
Published: September 2021

AbstractRecently, heparin-induced thrombocytopenia (HIT) after vaccination with the vaccines manufactured by AstraZeneca and Pfizer–BioNTech has been published in the New England Journal of Medicine. These reports state that heparin was not used around the vaccination period in all cases. HIT after vaccination is more common in women; thus, heparinoid use can be suspected to induce HIT.
Cross-sectional and prospective associations of sleep, sedentary and active behaviors with mental health in older people: a compositional data analysis from the Seniors-ENRICA-2 study
Authors: Cabanas-Sánchez Verónica , Esteban-Cornejo Irene , García-Esquinas Esther , Ortolá Rosario , Ara Ignacio , Rodríguez-Gómez Irene , Chastin Sebastien F. M. , Rodríguez-Artalejo Fernando , Martínez-Gómez David 
Published: September 2021

Abstract
Background
Most studies on the effects of sleep, sedentary behavior (SB), and physical activity (PA) on mental health did not account for the intrinsically compositional nature of the time spent in several behaviors. Thus, we examined the cross-sectional and prospective associations of device-measured compositional time in sleep, SB, light PA (LPA) and moderate-to-vigorous PA (MVPA) with depression symptoms, loneliness, happiness, and global mental health in older people (≥ 65 years).

Methods
Data were taken from the Seniors-ENRICA-2 study, with assessments in 2015–2017 (wave 0) and 2018–2019 (wave 1). Time spent in sleep, SB, LPA and MVPA was assessed by wrist-worn accelerometers. Depression symptoms, loneliness, happiness, and global mental health were self-reported using validated questionnaires. Analyses were performed using a compositional data analysis (CoDA) paradigm and adjusted for potential confounders.

Results
In cross-sectional analyses at wave 0 (n = 2489), time-use composition as a whole was associated with depression and happiness (all p < 0.01). The time spent in MVPA relative to other behaviors was beneficially associated with depression (γ = -0.397, p < 0.001), loneliness (γ = -0.124, p = 0.017) and happiness (γ = 0.243, p < 0.001). Hypothetically, replacing 30-min of Sleep, SB or LPA with MVPA was beneficially cross-sectionally related with depression (effect size [ES] ranged -0.326 to -0.246), loneliness (ES ranged -0.118 to -0.073), and happiness (ES ranged 0.152 to 0.172). In prospective analyses (n = 1679), MVPA relative to other behaviors at baseline, was associated with favorable changes in global mental health (γ = 0.892, p = 0.049). We observed a beneficial prospective effect on global mental health when 30-min of sleep (ES = 0.521), SB (ES = 0.479) or LPA (ES = 0.755) were theoretically replaced for MVPA.

Conclusions
MVPA was cross-sectionally related with reduced depression symptoms and loneliness and elevated level of happiness, and prospectively related with enhanced global mental health. Compositional isotemporal analyses showed that hypothetically replacing sleep, SB or LPA with MVPA could result in modest but significantly improvements on mental health indicators. Our findings add evidence to the emerging body of research on 24-h time-use and health using CoDA and suggest an integrated role of daily behaviors on mental health in older people.
Identification of circulating sphingosine kinase-related metabolites for prediction of type 2 diabetes
Authors: Chen Qi , Wang Wei , Xia Ming-Feng , Lu You-li , Bian Hua , Yu Chen , Li Xiao-Ying , Vadas Mathew A. , Gao Xin , Lin Huan-Dong , Xia Pu 
Published: September 2021

AbstractBackgroundSphingosine Kinase (SphK) that catalyzes sphingosine (Sph) to sphingosine 1-phosphate (S1P), plays a key role in both sphingolipid metabolism and cellular signaling. While SphK has been implicated in type 2 diabetes mellitus (T2DM), it is unexplored in humans. Herein, we investigated whether circulating SphK-related metabolites are associated with T2DM incidence in an established prospective cohort.MethodsLevels of SphK-related sphingolipid metabolites, including Sph, S1P, dihydrosphingosine (dhSph) and dihydro-S1P (dhS1P) in serum were measured by targeted-lipidomic analyses. By accessing to an established prospective cohort that involves a total of 2486 non-diabetic adults at baseline, 100 subjects who developed T2DM after a mean follow-up of 4.2-years, along with 100 control subjects matched strictly with age, sex, BMI and fasting glucose, were randomly enrolled for the present study.ResultsComparison with the control group, medians of serum dhS1P and dhS1P/dhSph ratio at baseline were elevated significantly prior to the onset of T2DM. Each SD increment of dhS1P and dhS1P/dhSph ratio was associated with 53.5% and 54.1% increased risk of incident diabetes, respectively. The predictive effect of circulating dhS1P and dhS1P/dhSph ratio on T2DM incidence was independent of conventional risk factors in multivariate regression models. Furthermore, combination of serum dhS1P and dhS1P/dhSph ratio with conventional clinical indices significantly improved the accuracy of T2DM prediction (AUROC, 0.726), especially for normoglycemic subjects (AUROC, 0.859).ConclusionCirculating levels of dhS1P and dhS1P/dhSph ratio are strongly associated with increased risk of T2DM, and could serve as a useful biomarker for prediction of incident T2DM in normoglycemic populations.
Galantamine prevents and reverses neuroimmune induction and loss of adult hippocampal neurogenesis following adolescent alcohol exposure
Authors: Macht Victoria , Vetreno Ryan , Elchert Natalie , Crews Fulton 
Published: September 2021

AbstractBackgroundBinge ethanol exposure during adolescence reduces hippocampal neurogenesis, a reduction which persists throughout adulthood despite abstinence. This loss of neurogenesis, indicated by reduced doublecortin+ immunoreactivity (DCX+IR), is paralleled by an increase in hippocampal proinflammatory signaling cascades. As galantamine, a cholinesterase inhibitor, has anti-inflammatory actions, we tested the hypothesis that galantamine would prevent (study 1) or restore (study 2) AIE induction of proinflammatory signals within the hippocampus as well as AIE-induced loss of hippocampal neurogenesis.MethodsGalantamine (4 mg/kg) or vehicle (saline) was administered to Wistar rats during adolescent intermittent ethanol (AIE; 5.0 g/kg ethanol, 2 days on/2 days off, postnatal day [P] 25-54) (study 1, prevention) or after AIE during abstinent maturation to adulthood (study 2, restoration).ResultsResults indicate AIE reduced DCX+IR and induced cleaved caspase3 (Casp3) in DCX-expressing immature neurons. Excitingly, AIE induction of activated Casp3 in DCX-expressing neurons is both prevented and reversed by galantamine treatment, which also resulted in prevention and restoration of neurogenesis (DCX+IR). Similarly, galantamine prevented and/or reversed AIE induction of proinflammatory markers, including the chemokine (C-C motif) ligand 2 (CCL2), cyclooxygenase-2 (COX-2), and high mobility group box 1 (HMGB1) protein, suggesting that AIE induction of proinflammatory signaling mediates both cell death cascades and hippocampal neurogenesis. Interestingly, galantamine treatment increased Ki67+IR generally as well as increased pan-Trk expression specifically in AIE-treated rats but failed to reverse AIE induction of NADPH-oxidase (gp91phox).ConclusionsCollectively, our studies suggest that (1) loss of neurogenesis after AIE is mediated by persistent induction of proinflammatory cascades which drive activation of cell death machinery in immature neurons, and (2) galantamine can prevent and restore AIE disruptions in the hippocampal environmental milieu to then prevent and restore AIE-mediated loss of neurogenesis.
NAD+ improves cognitive function and reduces neuroinflammation by ameliorating mitochondrial damage and decreasing ROS production in chronic cerebral hypoperfusion models through Sirt1/PGC-1α pathway
Authors: Zhao Yao , Zhang Jiawei , Zheng Yaling , Zhang Yaxuan , Zhang Xiao Jie , Wang Hongmei , Du Yu , Guan Jian , Wang Xiuzhe , Fu Jianliang 
Published: September 2021

Abstract
Background
Microglial-mediated neuroinflammation plays an important role in vascular dementia, and modulating neuroinflammation has emerged as a promising treatment target. Nicotinamide adenine dinucleotide (NAD+) shows anti-inflammatory and anti-oxidant effects in many neurodegenerative disease models, but its role in the chronic cerebral hypoperfusion (CCH) is still unclear.

Methods
The bilateral common carotid artery occlusion (BCCAO) was performed to establish CCH models in Sprague-Dawley rats. The rats were given daily intraperitoneal injection of NAD+ for 8 weeks. The behavioral test and markers for neuronal death and neuroinflammation were analyzed. Mitochondrial damage and ROS production in microglia were also assessed. RNA-seq was performed to investigate the mechanistic pathway changes. For in vitro studies, Sirt1 was overexpressed in BV2 microglial cells to compare with NAD+ treatment effects on mitochondrial injury and neuroinflammation.

Results
NAD+ administration rescued cognitive deficits and inhibited neuroinflammation by protecting mitochondria and decreasing ROS production in CCH rats. Results of mechanistic pathway analysis indicated that the detrimental effects of CCH might be associated with decreased gene expression of PPAR-γ co-activator1α (PGC-1α) and its upstream transcription factor Sirt1, while NAD+ treatment markedly reversed their decrease. In vitro study confirmed that NAD+ administration had protective effects on hypoxia-induced neuroinflammation and mitochondrial damage, as well as ROS production in BV2 microglia via Sirt1/PGC-1α pathway. Sirt1 overexpression mimicked the protective effects of NAD+ treatment in BV2 microglia.

Conclusions
NAD+ ameliorated cognitive impairment and dampened neuroinflammation in CCH models in vivo and in vitro, and these beneficial effects were associated with mitochondrial protection and ROS inhibition via activating Sirt1/PGC-1α pathway.
Influence of HFD-induced precocious puberty on neurodevelopment in mice
Authors: Bo Tingbei , Wen Jing , Gao Wenting , Tang Liqiu , Liu Min , Wang Dehua 
Published: September 2021

Abstract
Background
Precocious puberty is frequently associated with obesity, which will lead to long-term effects, especially on growth and reproduction. However, the effect of precocious puberty on children's neurodevelopment is still unknown.

Objectives
Here we evaluated the effect of High fat diet (HFD)-induced precocious puberty on neurodevelopment and behaviors of animals.

Methods
Ovaries sections were stained with hematoxylin–eosin (H&E) using standard techniques. Behavioral tests included elevated plus maze (EPM), open field exploration, Y-Maze, marble burying test, and novelty- suppressed feeding. The expression of genes related to puberty and neural development was detected by immunohistochemistry and Western blot.

Results
Our results showed HFD-induced precocious puberty increased the risk-taking behavior and decreased memory of mice. The content of Tyrosine hydroxylase (TH) and Arginine vasopressin (AVP) in hypothalamus were higher in HFD group than control group. Although the recovery of normal diet will gradually restore the body fat and other physiological index of mice, the anxiety increases in adult mice, and the memory is also damaged.

Conclusions
These findings describe the sensitivity of mice brain to HFD-induced precocious puberty and the irrecoverability of neural damage caused by precocious puberty. Therefore, avoiding HFD in childhood is important to prevent precocious puberty and neurodevelopmental impairment in mice.

Graphic abstract
Interactions of brain, blood, and CSF: a novel mathematical model of cerebral edema
Authors: Doron Omer , Zadka Yuliya , Barnea Ofer , Rosenthal Guy 
Published: September 2021

Abstract
Background
Previous models of intracranial pressure (ICP) dynamics have not included flow of cerebral interstitial fluid (ISF) and changes in resistance to its flow when brain swelling occurs. We sought to develop a mathematical model that incorporates resistance to the bulk flow of cerebral ISF to better simulate the physiological changes that occur in pathologies in which brain swelling predominates and to assess the model’s ability to depict changes in cerebral physiology associated with cerebral edema.

Methods
We developed a lumped parameter model which includes a representation of cerebral ISF flow within brain tissue and its interactions with CSF flow and cerebral blood flow (CBF). The model is based on an electrical analog circuit with four intracranial compartments: the (1) subarachnoid space, (2) brain, (3) ventricles, (4) cerebral vasculature and the extracranial spinal thecal sac. We determined changes in pressure and volume within cerebral compartments at steady-state and simulated physiological perturbations including rapid injection of fluid into the intracranial space, hyperventilation, and hypoventilation. We simulated changes in resistance to flow or absorption of CSF and cerebral ISF to model hydrocephalus, cerebral edema, and to simulate disruption of the blood–brain barrier (BBB).

Results
The model accurately replicates well-accepted features of intracranial physiology including the exponential-like pressure–volume curve with rapid fluid injection, increased ICP pulse pressure with rising ICP, hydrocephalus resulting from increased resistance to CSF outflow, and changes associated with hyperventilation and hypoventilation. Importantly, modeling cerebral edema with increased resistance to cerebral ISF flow mimics key features of brain swelling including elevated ICP, increased brain volume, markedly reduced ventricular volume, and a contracted subarachnoid space. Similarly, a decreased resistance to flow of fluid across the BBB leads to an exponential-like rise in ICP and ventricular collapse.

Conclusions
The model accurately depicts the complex interactions that occur between pressure, volume, and resistances to flow in the different intracranial compartments under specific pathophysiological conditions. In modelling resistance to bulk flow of cerebral ISF, it may serve as a platform for improved modelling of cerebral edema and blood–brain barrier disruption that occur following brain injury.
Towards a better understanding of Fagopyrum dibotrys: a systematic review
Authors: Zhang Le-Le , He Yan , Sheng Feiya , Hu Ying-Fan , Song Yu , Li Wei , Chen Jiarong , Zhang Jinming , Zou Liang 
Published: September 2021

AbstractFagopyrum dibotrys (F. dibotrys) (D.Don) H.Hara is a well-known edible herbal medicine in Asian countries. It has been widely used for the treatment of lung diseases, swelling, etc., and is also an important part of many Chinese medicine prescriptions. At present, more than 100 compounds have been isolated and identified from F. dibotrys, and these compounds can be primarily divided into flavonoids, phenols, terpenes, steroids, and fatty acids. Flavonoids and phenolic compounds are considered to be the main active ingredients of F. dibotrys. Previous pharmacological studies have shown that F. dibotrys possesses anti-inflammatory, anti-cancer, anti-oxidant, anti-bacterial, and anti-diabetic activities. Additional studies on functional genes have led to a better understanding of the metabolic pathways and regulatory factors related with the flavonoid active ingredients in F. dibotrys. In this paper, we systemically reviewed the research advances on the phytochemistry and pharmacology of F. dibotrys, as well as the functional genes related to the synthesis of active ingredients, aiming to promote the development and utilization of F. dibotrys.