bluuebunny/crossref_metadata_2025_split huggingface dataset:
Icaritin promotes apoptosis and inhibits proliferation by down-regulating AFP gene expression in hepatocellular carcinoma
Authors: Li Hui , Liu Yujuan , Jiang Wei , Xue Junhui , Cheng Yuning , Wang Jiyin , Yang Ruixiang , Zhang Xiaowei 
Published: March 2021

Abstract
Background
Icaritin, an active ingredient of the Chinese herb Epimedium, plays an anti-tumor role in liver cancer by inhibiting the proliferation of hepatocellular cells and promoting their apoptosis. In China, phase II and a large phase III clinical trial of icaritin reagent for the treatment of hepatocellular cancer is under-going, but the specific mechanism of icaritin action was unclear. Alpha-fetoprotein (AFP), an oncofetal protein, produced in the healthy fetal liver and yolk sac. Intracellular AFP promoted cellular proliferation and inhibited cellular apoptosis in hepatocellular carcinoma (HCC). The study was aimed to investigate the effect of icaritin on HCC through p53/AFP pathway.

Methods
Real-time RT PCR and western blot were used to detect p53 and AFP expression levels in HCC cells treated with icaritin. The mechanism of icaritin affecting p53 expression was verified by ubiquitination experiment, and the binding activity of icaritin on p53 in AFP promoter region was verified by luciferase experiment. EdU, MTT and flow cytometry were used to determine whether icaritin affected HCC cellular proliferation and apoptosis through p53/ AFP pathway. Expression levels of p53 and AFP in xenograft mouse model were determined by western blotting.

Results
Our results showed icaritin inhibited AFP expression at mRNA and protein level. AFP was also identified as the target gene of the p53 transcription factor. Icaritin abrogated murine double minute (Mdm) 2-mediated p53 ubiquitination degradation to improve the stability of p53. Up-regulated p53 protein levels then transcriptionally inhibited the AFP promoter. Icaritin-mediated decrease of AFP through Mdm2/p53 pathways inhibited HCC cellular proliferation and promoted HCC cellular apoptosis.

Conclusion
Our findings revealed the mechanism of icaritin in promoting apoptosis and inhibiting proliferation in liver cancer cells. The regulatory mechanism of icaritin in AFP protein down-regulation provides a theoretical and experimental basis for further research into new drugs for the treatment of liver cancer.
Factors related to age at depression onset: the role of SLC6A4 methylation, sex, exposure to stressful life events and personality in a sample of inpatients suffering from major depression
Authors: Sanwald Simon , Widenhorn-Müller Katharina , Schönfeldt-Lecuona Carlos ,   GenEmo Research Group, Connemann Bernhard J. , Gahr Maximilian , Kammer Thomas , Montag Christian , Kiefer Markus 
Published: March 2021

Abstract
Background
An early onset of depression is associated with higher chronicity and disability, more stressful life events (SLEs), higher negative emotionality as described by the primary emotion SADNESS and more severe depressive symptomatology compared to depression onset later in life. Additionally, methylation of the serotonin transporter gene (SLC6A4) is associated with SLEs and depressive symptoms.

Methods
We investigated the relation of SLEs, SLC6A4 methylation in peripheral blood, the primary emotions SADNESS and SEEKING (measured by the Affective Neuroscience Personality Scales) as well as depressive symptom severity to age at depression onset in a sample of N = 146 inpatients suffering from major depression.

Results
Depressed women showed higher SADNESS (t (91.05) = − 3.17, p = 0.028, d = − 0.57) and higher SLC6A4 methylation (t (88.79) = − 2.95, p = 0.02, d = − 0.55) compared to men. There were associations between SLEs, primary emotions and depression severity, which partly differed between women and men. The Akaike information criterion (AIC) indicated the selection of a model including sex, SLEs, SEEKING and SADNESS for the prediction of age at depression onset. SLC6A4 methylation was not related to depression severity, age at depression onset or SLEs in the entire group, but positively related to depression severity in women.

Conclusions
Taken together, we provide further evidence that age at depression onset is associated with SLEs, personality and depression severity. However, we found no associations between age at onset and SLC6A4 methylation. The joint investigation of variables originating in biology, psychology and psychiatry could make an important contribution to understanding the development of depressive disorders by elucidating potential subtypes of depression.
Verbal learning impairment in adolescents with methamphetamine use disorder: a cross-sectional study
Authors: Basedow Lukas Andreas , Kuitunen-Paul Sören , Wiedmann Melina Felicitas , Ehrlich Stefan , Roessner Veit , Golub Yulia 
Published: March 2021

AbstractBackgroundMethamphetamine (MA) use has been shown to be associated with deficits in impulsivity, verbal learning, and working memory. Additionally, methamphetamine use disorder (MUD) is related to various brain changes, especially in adolescent users who might be more vulnerable to detrimental effects on brain development. However, little is known about the relationship between adolescent MA use and cognitive impairment. This cross-sectional study aims to explore how the presence of a MUD in adolescents is related to impairments of verbal memory, inhibition, and alertness.MethodsN = 18 psychiatric outpatients with MUD were matched in terms of depressivity, age, and gender ton = 18 adolescents with other substance use disorders (SUDs), as well asn = 18 controls without SUDs. We compared these three groups on the Verbal Learning and Memory Task (VLMT), and the alertness and go/noGo subtests of the Test of Attentional Performance (TAP). Additionally, Spearman’s rank order correlation coefficients were calculated to investigate whether cognitive functioning was directly associated with frequency of past year MA use.ResultsThe three groups differed significantly in their verbal learning performance (H(2) = 11.7,p = .003, ηp2 = .19), but not in short-term memory, inhibition, cued recall, or alertness. Post hoc tests revealed significant differences in verbal learning between the MA using group and the control group without a SUD (U = 56.5,p = .001, ηp2 = .31). Frequency of past year MA use correlated negatively with short-term memory (ρ = −.25,p < .01) and verbal learning (ρ = −.41,p < .01). No other cognitive variables correlated significantly with MA use frequency. Significantp-values were considered significant after Bonferroni correction.ConclusionsAdolescent MUD outpatients with regular MA use show specific impairment in verbal learning performance, but not in other basal cognitive functions when compared to adolescents without a MUD. Verbal learning and short-term memory performance is negatively associated with the frequency of MA use. Future research should apply longitudinal designs to investigate long-term effects of methamphetamine and reversibility of these effects on cognitive functioning.
Social capital and sleep disorders in Tibet, China
Authors: Ciren Wangla , Yu Wanqi , Nima Qucuo , Xiao Xiong , Zhou Junmin , Suolang Deji , Li Yajie , Zhao Xing , Jia Peng , Yang Shujuan 
Published: March 2021

Abstract
Objective
Sleep plays an important role in the health and well-being of middle aged and elderly people, and social capital may be one of the important factors for sleep disorders. This study aimed to understand the relationship between social capital and sleep disorders in a unique region of China –Tibet that generally has the disadvantaged economic status compared to other parts of China.

Methods
The study was based on Tibetan data from The China Multi-Ethnic Cohort (CMEC) and was conducted from May 2018 to September 2019. A total of 3194 Tibetans aged > 50 were selected from the community population by multi-stage stratified cluster sampling. Social capital was measured using two validated health-related social capital scales, family/community and society.. Sleep disorders were measured as the presence of disorders of initiating and maintaining sleep, early morning awakening, or daytime dysfunction. Logistic regression models were applied to examine the association between social capital and sleep disorders.

Results
39.9% (1271/3194) of the participants had sleep disorders. In addition, after controlling for all potential variables, family social capital was significantly negatively associated with sleep disorders (OR = 0.95, P < 0.05), while community and society social capital was not associated with sleep disorders. Then, when we did all the sex-stratified analyses, the significant association between social capital and sleep disorders was found only in women (OR = 0.94, P < 0.05), while no association was found in males; neither males nor females showed any association with community and society social capital.

Conclusion
Our study would help to better understand the extent of health inequality in China, and guide future interventions, strategies and policies to promote sleep quality in low-income areas, taking into account both the role of Tibetan specific cultural traditions, lifestyles and religious beliefs in social capital and the gender differences in social capital.
Understanding disadvantaged adolescents’ perception of health literacy through a systematic development of peer vignettes
Authors: Goss Hannah R. , McDermott Clare , Hickey Laura , Issartel Johann , Meegan Sarah , Morrissey Janis , Murrin Celine , Peers Cameron , Smith Craig , Spillane Ailbhe , Belton Sarahjane 
Published: March 2021

Abstract
Background
Adolescence represents a crucial phase of life where health behaviours, attitudes and social determinants can have lasting impacts on health quality across the life course. Unhealthy behaviour in young people is generally more common in low socioeconomic groups. Nevertheless, all adolescents should have a fair opportunity to attain their full health potential. Health literacy is positioned as a potential mediating factor to improve health, but research regarding health literacy in adolescents and socially disadvantaged populations is limited. As part of Phase one of the Ophelia (OPtimising HEalth LIterAcy) framework, The purpose of this study was to explore the perceptions of socially disadvantaged Irish adolescents in relation to health literacy and related behaviours, and utilise this data to develop relevant vignettes.

Methods
A convergent mixed method design was used to co-create the vignettes. Questionnaires were completed by 962 adolescents (males n = 553, females n = 409, Mean age = 13.97 ± 0.96 years) from five participating disadvantaged schools in Leinster, Ireland. Focus groups were also conducted in each school (n = 31). Results were synthesised using cluster and thematic analysis, to develop nine vignettes that represented typical male and female subgroups across the schools with varying health literacy profiles. These vignettes were then validated through triangular consensus with students, teachers, and researchers.

Discussion
The co-creation process was a participatory methodology which promoted the engagement and autonomy of the young people involved in the project. The vignettes themselves provide an authentic and tangible description of the health issues and health literacy profiles of adolescents in this context. Application of these vignettes in workshops involving students and teachers, will enable meaningful engagement in the discussion of health literacy and health-related behaviours in Irish young people, and the potential co-designing of strategies to address health literacy in youth.

Conclusion
As guided by the Ophelia framework, the use of authentic, interactive and participatory research methods, such as the co-creation of vignettes, is particularly important in groups that are underserved by traditional research methods. The approach used in this study could be adapted to other contexts to represent and understand stakeholders’ perceptions of health, with a view to explore, and ultimately improve, health literacy.
Prosthetic valve detachment complicated with intervalvular fibrous body destruction in Behcet’s disease: a case report
Authors: Qin Xiaoli , Liang Weitao , Yue Honghua , Wu Zhong 
Published: March 2021

Abstract
Background
Prosthetic valve detachment is not rare after aortic valve replacement in Behcet’s disease. However, destruction of the intervalvular fibrous body (IFB) due to Behcet’s disease was rarely reported.

Case presentation
We report a case of 30 year-old woman, with valve detachment and IFB separation. The patient received aortic valve replacement three months ago. Her medical history included recurrent oral ulcers and cutaneous lesions. Finally, reoperation was performed and peri-operative steroid therapy was carried out.

Conclusions
The case presented a rare complication of valve detachment in Behcet’s disease.
Posterior thoracolumbar hemivertebra resection and short-segment fusion in congenital scoliosis: surgical outcomes and complications with more than 5-year follow-up
Authors: Bao Beixi , Su Qingjun , Hai Yong , Yin Peng , Zhang Yaoshen , Zhu Shiqi , Sun Zhencheng 
Published: March 2021

Abstract
Background
Treatment of congenital hemivertebra is challenging and data on long-term follow-up (≥ 5 years) are lacking. This study evaluated the surgical outcomes of posterior thoracolumbar hemivertebra resection and short-segment fusion with pedicle screw fixation for treatment of congenital scoliosis with over 5-year follow-up.

Methods
This study evaluated 27 consecutive patients with congenital scoliosis who underwent posterior thoracolumbar hemivertebra resection and short-segment fusion from January 2007 to January 2015. Segmental scoliosis, total main scoliosis, compensatory cranial curve, compensatory caudal curve, trunk shift, shoulder balance, segmental kyphosis, and sagittal balance were measured on radiographs. Radiographic outcomes and all intraoperative and postoperative complications were recorded.

Results
The segmental main curve was 40.35° preoperatively, 11.94° postoperatively, and 13.24° at final follow-up, with an average correction of 65.9%. The total main curve was 43.39° preoperatively, 14.13° postoperatively, and 16.06° at final follow-up, with an average correction of 60.2%. The caudal and cranial compensatory curves were corrected from 15.78° and 13.21° to 3.57° and 6.83° postoperatively and 4.38° and 7.65° at final follow-up, with an average correction of 69.2% and 30.3%, respectively. The segmental kyphosis was corrected from 34.30° to 15.88° postoperatively and 15.12° at final follow-up, with an average correction of 61.9%. A significant correction (p < 0.001) in segmental scoliosis, total main curve, caudal compensatory curves and segmental kyphosis was observed from preoperative to the final follow-up. The correction in the compensatory cranial curve was significant between preoperative and postoperative and 2-year follow-up (p < 0.001), but a statistically significant difference was not observed between the preoperative and final follow-up (p > 0.001). There were two implant migrations, two postoperative curve progressions, five cases of proximal junctional kyphosis, and four cases of adding-on phenomena.

Conclusion
Posterior thoracolumbar hemivertebra resection after short-segment fusion with pedicle screw fixation in congenital scoliosis is a safe and effective method for treatment and can achieve rigid fixation and deformity correction.
A cost-effectiveness analysis of community water fluoridation for schoolchildren
Authors: Cronin Jodi , Moore Stephen , Harding Máiréad , Whelton Helen , Woods Noel 
Published: March 2021

Abstract
Background
Community water fluoridation (CWF), the controlled addition of fluoride to the water supply for the prevention of dental caries (tooth decay), is considered a safe and effective public health intervention. The Republic of Ireland (Ireland) is the only country in Europe with a legislative mandate for the fluoridation of the public water supply, a key component of its oral health policy. However, more recently, there has been an increase in public concern around the relevance of the intervention given the current environment of multiple fluoride sources and a reported increase in the prevalence of enamel fluorosis. The aim of this economic analysis is to provide evidence to inform policy decisions on whether the continued public investment in community water fluoridation remains justified under these altered circumstances.

Methods
Following traditional methods of economic evaluation and using epidemiological data from a representative sample of 5-, 8-, and 12-year-old schoolchildren, this cost-effectiveness analysis, conducted from the health-payer perspective, compared the incremental costs and consequences associated with the CWF intervention to no intervention for schoolchildren living in Ireland in 2017. A probabilistic model was developed to simulate the potential lifetime treatment savings associated with the schoolchildren’s exposure to the intervention for one year.

Results
In 2017, approximately 71% of people living in Ireland had access to a publicly provided fluoridated water supply at an average per capita cost to the state of €2.15. The total cost of CWF provision to 5-, 8-, and 12-year-old schoolchildren (n = 148,910) was estimated at €320,664, and the incremental cost per decayed, missing, or filled tooth (d3vcmft/D3vcMFT) prevented was calculated at €14.09. The potential annual lifetime treatment savings associated with caries prevented for this cohort was estimated at €2.95 million. When the potential treatment savings were included in the analysis, the incremental cost per d3vcmft/D3vcMFT prevented was -€115.67, representing a cost-saving to the health-payer and a positive return on investment. The results of the analysis were robust to both deterministic and probability sensitivity analyses.

Conclusion
Despite current access to numerous fluoride sources and a reported increase in the prevalence of enamel fluorosis, CWF remains a cost-effective public health intervention for Irish schoolchildren.
Development of a novel global rating scale for objective structured assessment of technical skills in an emergency medical simulation training
Authors: Zoller Andreas , Hölle Tobias , Wepler Martin , Radermacher Peter , Nussbaum Benedikt L. 
Published: March 2021

Abstract
Background
Medical simulation trainings lead to an improvement in patient care by increasing technical and non-technical skills, procedural confidence and medical knowledge. For structured simulation-based trainings, objective assessment tools are needed to evaluate the performance during simulation and the learning progress. In surgical education, objective structured assessment of technical skills (OSATS) are widely used and validated. However, in emergency medicine and anesthesia there is a lack of validated assessment tools for technical skills. Thus, the aim of the present study was to develop and validate a novel Global Rating Scale (GRS) for emergency medical simulation trainings.

Methods
Following the development of the GRS, 12 teams of different experience in emergency medicine (4th year medical students, paramedics, emergency physicians) were involved in a pre-hospital emergency medicine simulation scenario and assessed by four independent raters. Subsequently, interrater reliability and construct validity of the GRS were analyzed. Moreover, the results of the GRS were cross-checked with a task specific check list. Data are presented as median (minimum; maximum).

Results
The GRS consists of ten items each scored on a 5-point Likert scale yielding a maximum of 50 points. The median score achieved by novice teams was 22.75 points (17;30), while experts scored 39.00 points (32;47). The GRS overall scores significantly discriminated between student-guided teams and expert teams of emergency physicians (p = 0.005). Interrater reliability for the GRS was high with a Kendall’s coefficient of concordance W ranging from 0.64 to 0.90 in 9 of 10 items and 0.88 in the overall score.

Conclusion
The GRS represents a promising novel tool to objectively assess technical skills in simulation training with high construct validity and interrater reliability in this pilot study.
Assessing elderly’s functional balance and mobility via analyzing data from waist-mounted tri-axial wearable accelerometers in timed up and go tests
Authors: Yu Lisha , Zhao Yang , Wang Hailiang , Sun Tien-Lung , Murphy Terrence E. , Tsui Kwok-Leung 
Published: March 2021

AbstractBackgroundPoor balance has been cited as one of the key causal factors of falls. Timely detection of balance impairment can help identify the elderly prone to falls and also trigger early interventions to prevent them. The goal of this study was to develop a surrogate approach for assessing elderly’s functional balance based on Short Form Berg Balance Scale (SFBBS) score.MethodsData were collected from a waist-mounted tri-axial accelerometer while participants performed a timed up and go test. Clinically relevant variables were extracted from the segmented accelerometer signals for fitting SFBBS predictive models. Regularized regression together with random-shuffle-split cross-validation was used to facilitate the development of the predictive models for automatic balance estimation.ResultsEighty-five community-dwelling older adults (72.12 ± 6.99 year) participated in our study. Our results demonstrated that combined clinical and sensor-based variables, together with regularized regression and cross-validation, achieved moderate-high predictive accuracy of SFBBS scores (mean MAE = 2.01 and mean RMSE = 2.55). Step length, gender, gait speed and linear acceleration variables describe the motor coordination were identified as significantly contributed variables of balance estimation. The predictive model also showed moderate-high discriminations in classifying the risk levels in the performance of three balance assessment motions in terms of AUC values of 0.72, 0.79 and 0.76 respectively.ConclusionsThe study presented a feasible option for quantitatively accurate, objectively measured, and unobtrusively collected functional balance assessment at the point-of-care or home environment. It also provided clinicians and elderly with stable and sensitive biomarkers for long-term monitoring of functional balance.