bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and validation of cuproptosis-related genes in acetaminophen-induced liver injury using bioinformatics analysis and machine learning
Authors: Guo Zhenya , Liu Jiaping , Liang Guozhi , Liang Haifeng , Zhong Mingbei , Tomlinson Stephen , He Songqing , Ouyang Guoqing , Yuan Guandou 
Published: June 2024

BackgroundAcetaminophen (APAP) is commonly used as an antipyretic analgesic. However, acetaminophen overdose may contribute to liver injury and even liver failure. Acetaminophen-induced liver injury (AILI) is closely related to mitochondrial oxidative stress and dysfunction, which play critical roles in cuproptosis. Here, we explored the potential role of cuproptosis-related genes (CRGs) in AILI.MethodsThe gene expression profiles were obtained from the Gene Expression Omnibus database. The differential expression of CRGs was determined between the AILI and control samples. Protein protein interaction, correlation, and functional enrichment analyses were performed. Machine learning was used to identify hub genes. Immune infiltration was evaluated. The AILI mouse model was established by intraperitoneal injection of APAP solution. Quantitative real-time PCR and western blotting were used to validate hub gene expression in the AILI mouse model. The copper content in the mouse liver samples and AML12 cells were quantified using a colorimetric assay kit. Ammonium tetrathiomolybdate (ATTM), was administered to mouse models and AML12 cells in order to investigate the effects of copper chelator on AILI.ResultsThe analysis identified 7,809 differentially expressed genes, 4,245 of which were downregulated and 3,564 of which were upregulated. Four optimal feature genes (OFGs; SDHB, PDHA1, NDUFB2, and NDUFB6) were identified through the intersection of two machine learning algorithms. Further nomogram, decision curve, and calibration curve analyses confirmed the diagnostic predictive efficacy of the four OFGs. Enrichment analysis indicated that the OFGs were involved in multiple pathways, such as IL-17 pathway and chemokine signaling pathway, that are related to AILI progression. Immune infiltration analysis revealed that macrophages were more abundant in AILI than in control samples, whereas eosinophils and endothelial cells were less abundant. Subsequently, the AILI mouse model was successfully established, and histopathological analysis using hematoxylin–eosin staining along with liver function tests revealed a significant induction of liver injury in the APAP group. Consistent with expectations, both mRNA and protein levels of the four OFGs exhibited a substantial decrease. The administration of ATTAM effectively mitigates copper elevation induced by APAP in both mouse model and AML12 cells. However, systemic administration of ATTM did not significantly alleviate AILI in the mouse model.ConclusionThis study first revealed the potential role of CRGs in the pathological process of AILI and offered novel insights into its underlying pathogenesis.
SFRP4 protein expression is reduced in high grade astrocytomas which is not caused by the methylation of its promoter
Authors: Kafka Anja , Pećina-Šlaus Nives , Drmić Denis , Bukovac Anja , Njirić Niko , Žarković Kamelija , Jakovčević Antonia 
Published: June 2024

IntroductionEpigenetics play a vital role in stratifying CNS tumors and gliomas. The importance of studying Secreted frizzled-related protein 4 (SFRP4) in gliomas is to improve diffuse glioma methylation profiling. Here we examined the methylation status of SFRP4 promoter and the level of its protein expression in diffuse gliomas WHO grades 2–4.MethodsSFRP4 expression was detected by immunohistochemistry and evaluated semi-quantitatively. In the tumor hot-spot area, the intensity of protein expression in 200 cells was determined using ImageJ (National Institutes of Health, United States). The assessment of immunopositivity was based on the IRS score (Immunoreactivity Score). Promoter methylation was examined by methylation specific-PCR (MSP) in fifty-one diffuse glioma samples and appropriate controls. Isolated DNA was treated with bisulfite conversion and afterwards used for MSP. Public databases (cBioPortal, COSMIC and LOVD) were searched to corroborate the results.Results and discussionSFRP4 protein expression in glioblastomas was very weak or non-existent in 86.7% of samples, moderate in 13.3%, while strong expression was not observed. The increase in astrocytoma grade resulted in SFRP4 protein decrease (p = 0.008), indicating the loss of its antagonistic role in Wnt signaling. Promoter methylation of SFRP4 gene was found in 16.3% of cases. Astrocytomas grade 2 had significantly more methylated cases compared to grade 3 astrocytomas (p = 0.004) and glioblastomas (p &lt; 0.001), which may indicate temporal niche of methylation in grade 2. Furthermore, the expression levels of SFRP4 were high in samples with methylated SFRP4 promoter and low or missing in unmethylated cases (Pearson’s R = −0.413; p = 0.003). We also investigated the association of SFRP4 changes to key Wnt regulators GSK3β and DKK3 and established a positive correlation between methylations of SFRP4 and GSK3β (Pearson’s R = 0.323; p = 0.03). Furthermore, SFRP4 expression was correlated to unmethylated DKK3 (Chi square = 7.254; p = 0.027) indication that Wnt signaling antagonist is associated to negative regulator’s demethylation.ConclusionThe study contributes to the recognition of the significance of epigenetic changes in diffuse glioma indicating that restoring SFRP4 protein holds potential as therapeutic avenue. Reduced expression of SFRP4 in glioblastomas, not following promoter methylation pattern, suggests another mechanism, possible global methylation, that turns off SFRP4 expression in higher grades.
Dietary patterns suggest that dark chocolate intake may have an inhibitory effect on oral cancer: a Mendelian randomization study
Authors: Wang Hongwei , Zhang Zhaoyin , Wu Sijie , Zhu Yuanzhi , Liang Tao , Huang Xiong , Yao Jinguang 
Published: June 2024

BackgroundPrevious studies reported that variations in dietary intake patterns substantially impact human health, specifically tumorigenesis. However, confounding factors in previous cohort studies have obscured the relationship between dietary differences and the risk of oral cancer (OC).Materials and methodsWe developed an outcome dataset from genome-wide association studies (GWAS) data on three OCs within the GAME-ON project, using GWAS-META merging. We extracted 21 dietary exposures, including 10 dietary patterns, 6 vitamins, and 5 micronutrients, from the UK Biobank database, using the inverse variance weighting method as the primary statistical method. Sensitivity analysis was conducted to detect heterogeneity and pleiotropy. Serum metabolite concentrations were adjusted using multivariate Mendelian randomization.ResultsOf the 10 analyzed dietary patterns, 8 showed no significant association with the risk of developing OC. Consumption of dark chocolate (inverse variance weighted [IVW]: Odds ratio (OR) = 0.786, 95% confidence interval [CI]: 0.622–0.993, p = 0.044) and sweet pepper exhibited an inverse relationship with OC risk (IVW: OR = 0.757, 95% CI: 0.574–0.997, p = 0.048). Reverse MR analysis revealed no reverse causality. Furthermore, no significant correlation was observed between the intake of 6 vitamins and 5 micronutrients and the risk of developing OC. After using multivariable MR to adjust for serum caffeine, linoleate, theophylline, and theobromine metabolism levels, consuming dark chocolate was unrelated to a decreased risk of OC. After adjusting each serum metabolite individually, the observed p-values deviated from the original values to varying degrees, indicating that the components of dark chocolate could have different effects. Among these components, theophylline demonstrated the most significant inhibitory effect.ConclusionThis study demonstrated a causal relationship between the intake of dark chocolate and sweet peppers and a lower risk of OC. The components of dark chocolate could have different effects.
Association between nutritional literacy and nutrition label use in Chinese community residents
Authors: Yang Ling , Cui Yan , Du Jing , Liu Zihao , Duan Ying , Qi Qi , Liu Huaqing , Zhang Min 
Published: June 2024

IntroductionNutritional literacy (NL) has a critical influence on food choices. The objective of the present study was to examine the association of NL with nutrition label use.MethodsA cross-sectional study was conducted in Bengbu, China. In total, 955 adults were interviewed using a questionnaire designed for the present study to collect information on demographics, lifestyle, nutrition label use, and NL. Binary logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI) for nutrition label use and its predictive variables.ResultsIn total, 40.4% of the participants reported looking at nutrition label when purchasing prepackaged foods. NL was significantly positively associated with nutrition label use and specifically with checking nutrition facts table, purported nutrition benefits and purported health benefits. In terms of specific facets of NL, nutrition knowledge, applying skills, and critical skills were associated with nutrition label use. After stratification by monthly income and education, the association between NL and nutrition label use was discovered only in individuals with low monthly income. Additionally, nutrition knowledge was associated with nutrition label use only in adults with high education level, whereas applying skills were associated with nutrition label use only in those with low education level.ConclusionThe use of nutrition label remains low among Chinese community residents, especially the purported nutritional benefits and purported health benefits. NL is positively associated with nutrition label use, especially with respect to functional and critical NL, with differences based on socioeconomic status. The findings highlight the need for NL interventions targeting individuals with different levels of education and income to encourage use of nutrition label in China.
Understanding the support for gender-based harassment perpetrators: the role of closeness and empathy
Authors: Borges-Castells Nira , Betancor Verónica , Rodríguez-Pérez Armando 
Published: June 2024

IntroductionGender-based harassment is a pressing social challenge urgently demanding eradication. While social movements emphasize supporting victims, societal responses sometimes lean toward exculpating perpetrators. This study examines two factors influencing this exoneration: closeness to perpetrators and empathy focus.MethodsA total of 345 participants took part in an experimental design to assess how closeness to perpetrators (close vs. distant) and empathy focus (on the perpetrator vs. victim vs. control) impact the moral justification of harassment and the dehumanization of both parties.Results and discussionResults indicate that closeness and empathizing with perpetrators lead to greater leniency—more moral justification and less dehumanization of the perpetrator. Heightened moral justification for close perpetrators is mediated by increased empathy toward them and decreased empathy for victims, and reduced dehumanization of close perpetrators corresponds to heightened empathy toward them. This research highlights how closeness and empathy, two initially positive factors, can foster tolerance toward gender harassment.
Case report: Avoidant/restrictive food intake disorder after tonsillectomy
Authors: Ahmed Gellan K. , Karim Ahmed A. , Khedr Eman M. , Elbeh Khaled , Moheb Amira , Abokresha Marwa , Haridy Nourelhoda A. 
Published: June 2024

BackgroundAvoidant Restrictive Food Intake Disorder (ARFID) is a newly classified eating disorder that requires further understanding of its presentation. There is no previous report of ARFID in a child post-tonsillectomy. ARFID may be a potential negative outcome for children following oropharyngeal surgery.Case presentationA female child aged 10 years and 2 months presented with ARFID associated with depression, anxiety and nutritional deficiency following tonsillectomy. She had more difficulty in swallowing solids than fluids and had repeated vomiting and spitting food after chewing it. She became dehydrated and malnourished with a BMI of 10.5 and was misdiagnosed with myasthenic gravis.ConclusionsTo our knowledge, this is the first case report of ARFID in a child post-tonsillectomy. We discuss the pathophysiology of ARFID, which remains elusive, and recommend psychiatric assessment when evaluating children post operative tonsillectomy.
The attitudes of nonpsychiatric nurses towards mental disorders in China
Authors: Wang Qi-Kai , Wang Xu , Qiu Ya-Jing , Bao Wen-Xin , Chen Xia-Can , Xu Jia-Jun 
Published: June 2024

BackgroundFew studies have explored the associated factors of attitudes of nonpsychiatric nurses towards mental disorders. Therefore, this study is aimed to evaluate the attitudes of nonpsychiatric nurses towards mental disorders and especially explore the association between psychiatric clinical practice and these attitudes.MethodsA total of 1324 nonpsychiatric nurses and students majoring in nursing were recruited through an online questionnaire from December 2021 to March 2022 in Sichuan Province, China. Demographic information, personal care experience, psychiatric nursing education and the Community Attitudes towards the Mentally Ill (CAMI) were collected. A higher score indicates a stigmatizing attitude in the authoritarianism and social restrictiveness (SR) subscales and a positive attitude in the benevolence and community mental health ideology (CMHI) subscales. Multivariate linear regression was employed to analyze associated factors of attitudes towards mental disorders, and hierarchical linear regression was used to analyze the association between psychiatric clinical practice and the attitudes towards mental disorders.ResultsUnder the control of confounders, high education level, long residence in urban and personal care experience were positively correlated with score of authoritarianism and SR (p &lt; 0.05), and negatively correlated with score of benevolence (p &lt; 0.05). Long residence in urban and personal care experience were negatively correlated with score of CMHI (p &lt; 0.05). Hierarchical linear regression analysis showed that after adjusting for demographic information, psychiatric clinical practice was associated with lower score of benevolence (B = -0.09, 95%CI = -0.17 ~ -0.003, p = 0.043) and CMHI (B = -0.09, 95%CI = -0.17 ~ -0.01, p = 0.027), but the initial associations between psychiatric clinical practice and authoritarianism, SR disappeared.ConclusionsHigh education level, long residence in urban, personal care experience and the psychiatric clinical practice were associated with the discrimination of nonpsychiatric nurses towards mental disorders. Further exploring practical strategies to optimize the psychiatric clinical practice experience of nonpsychiatric nurses could help improve their attitudes towards mental disorders.
Selective orthotic constraint of lower limb movement during walking reveals new insights into neuromuscular adaptation
Authors: Hovorka Christopher F. , Kogler Géza F. , Chang Young-Hui , Gregor Robert J. 
Published: June 2024

IntroductionA concern expressed by the clinical community is that the constraint of motion provided by an ankle foot orthosis (AFO) may lead the user to become dependent on its stiffness, leading to learned non-use. To examine this, we hypothesized that using an experimental AFO-footwear combination (exAFO-FC) that constrains ankle motion during walking would result in reduced soleus and tibialis anterior EMG compared to free (exAFO-FC) and control (no AFO, footwear only) conditions.MethodA total of 14 healthy subjects walked at their preferred speed (1.34 ± 0.09 m·s-1) for 15 min, in three conditions, namely, control, free, and stop.ResultsDuring the stance phase of walking in the stop condition, ipsilateral soleus integrated EMG (iEMG) declined linearly, culminating in a 32.1% reduction compared to the control condition in the final 5 min interval of the protocol. In contrast, ipsilateral tibialis anterior iEMG declined in a variable fashion culminating in an 11.2% reduction compared to control in the final 5 min interval. During the swing phase, the tibialis anterior iEMG increased by 6.6% compared to the control condition during the final 5 min interval. The contralateral soleus and tibialis anterior exhibited increased iEMG in the stop condition.DiscussionAn AFO-FC functions as a biomechanical motion control device that influences the neural control system and alters the output of muscles experiencing constraints of motion.
Understanding access to general practice through the lens of candidacy: a critical review of the literature
Authors: Sinnott Carol , Ansari Akbar , Price Evleen , Fisher Rebecca , Beech Jake , Alderwick Hugh , Dixon-Woods Mary 
Published: June 2024

BackgroundDominant conceptualisations of access to health care are limited, framed in terms of speed and supply. The Candidacy Framework offers a more comprehensive approach, identifying diverse influences on how access is accomplished.AimTo characterise how the Candidacy Framework can explain access to general practice — an increasingly fraught area of public debate and policy.Design and settingQualitative review guided by the principles of critical interpretive synthesis.MethodWe conducted a literature review using an author-led approach, involving iterative analytically guided searches. Articles were eligible for inclusion if they related to the context of general practice, without geographical or time limitations. Key themes relating to access to general practice were extracted and synthesised using the Candidacy Framework.ResultsA total of 229 articles were included in the final synthesis. The seven features identified in the original Candidacy Framework are highly salient to general practice. Using the lens of candidacy demonstrates that access to general practice is subject to multiple influences that are highly dynamic, contingent, and subject to constant negotiation. These influences are socioeconomically and institutionally patterned, creating risks to access for some groups. This analysis enables understanding of the barriers to access that may exist, even though general practice in the UK is free at the point of care, but also demonstrates that a Candidacy Framework specific to this setting is needed.ConclusionThe Candidacy Framework has considerable value as a way of understanding access to general practice, offering new insights for policy and practice. The original framework would benefit from further customisation for the distinctive setting of general practice.
Relationship between research activity and the performance of English general practices: cross-sectional and longitudinal analyses
Authors: Gibson Jonathan , Kontopantelis Evangelos , Sutton Matthew , Boaz Annette , Little Paul , Mallen Christian , McManus Richard , Park Sophie , Usher-Smith Juliet , Bower Peter 
Published: June 2024

Background
Research activity usually improves outcomes by being translated into practice; however, there is developing evidence that research activity itself may improve the overall performance of healthcare organisations. Evidence that these relationships represent a causal impact of research activity is, however, less clear. Additionally, the bulk of the existing evidence relates to hospital settings, and it is not known if those relationships would also be found in general practice, where most patient contacts occur.

Aim
To test 1) whether there are significant relationships between research activity in general practice and organisational performance; and 2) whether those relationships are plausibly causal.

Design and setting
National data were analysed between 2008 and 2019, using cross-sectional and longitudinal analyses on general practices in England.

Method
Cross-sectional, panel, and instrumental variable analyses were employed to explore relationships between research activity (including measures from the National Institute for Health and Care Research Clinical Research Network and the Royal College of General Practitioners) and practice performance (including clinical quality of care, patient-reported experience of care, prescribing quality, and hospital admissions).

Results
In cross-sectional analyses, different measures of research activity were positively associated with several measures of practice performance, but most consistently with clinical quality of care and accident and emergency attendances. The associations were generally modest in magnitude; however, longitudinal analyses did not support a reliable causal relationship.

Conclusion
Similar to findings from hospital settings, research activity in general practice is associated with practice performance. There is less evidence that research is causing those improvements, although this may reflect the limited level of research activity in most practices. No negative impacts were identified, suggesting that research activity is a potential marker of quality and something that high-quality practices can deliver alongside their core responsibilities.
DEVELOPMENT OF SOCIAL MEDIA LEARNING ENGLISH VOCABULARY THROUGH SIGN LANGUAGE FOR THE HEARING IMPAIRED STUDENTS
Authors: Pieter Pieter , Palupi Tara Mustikaning , Mufidah Haura Nasywa , Nisa Hifdziyatun , Noval Ahmad Yazid 
Published: June 2024

This research examines the development of social media for learning English vocabulary using sign language as a learning method for hearing impaired students. With the advancement of technology and the incorporation of social media into the learning process, this study investigates how to use Instagram social media effectively to improve English vocabulary comprehension for students with hearing impairment using the Analysis, Design, Development, Implementation, and Evaluation (ADDIE) development model procedure. The research targets are seven hearing impairment students from SLB Negeri 02 Jakarta. Through the development of social media learning English vocabulary through sign language, students can learn English vocabulary by learning alphabets, names, numbers, and day names more easily. The results of this study show that learning videos developed through social media, particularly on Instagram, are beneficial for hearing impairment students who grasp foreign language learning materials, especially sign language using American Sign Language (ASL). The reviewers also gave the learning videos a feasibility evaluation, and they were pronounced appropriate for learning. As for the results of student tests, it is shown that the names and days show that the results of student test answers are all correct. However, in the number section, only three errors were found, and then in the alphabetical section, there were five errors. Developing technology-based learning media with microlearning methods, primarily through Instagram, can help hearing impairments students learn English. This opens up opportunities for developing more exciting and relevant learning content to facilitate English learning for students with special needs.