bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of the implementation of the Merdeka curriculum with Pancasila-profiled learners in early childhood education
Authors: Veryawan Veryawan , Hasibuan Rabitah Hanum , Anisaturrahmi Anisaturrahmi , Rosmiati Rosmiati , Fitriani Dewi , Hafiz Abdul , Rahma Rahma 
Published: March 2024

Merdeka curriculum is interpreted as a learning design that provides learning opportunities for children to learn with freedom and creative thinking, creating a generation of lifelong learners following the values of Pancasila. This research aims to analyze the implementation of the Merdeka curriculum with Pancasila-profiled learners in early childhood education. This research uses a systematic literature review using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) with three steps: planning, conducting, and reporting the review. The procedure through stages is the development of a review protocol, definition of inclusion and exclusion criteria, literature search in predetermined databases, critical appraisal, data extraction, and information synthesis. The result shows that implementing the Merdeka curriculum with the Pancasila student profiled in early childhood education is carried out in intra-curricular, extra-curricular, and school culture learning, starting with understanding the Merdeka curriculum and learning outcomes. Future research might delve deeper into assessing the holistic impact of the Merdeka Curriculum's Pancasila-student profiling on various aspects of early childhood development beyond values integration, such as cognitive, social, and emotional growth.
Exploring blood lipids-immunity associations following HBV vaccination: evidence from a large cross-sectional study
Authors: Yang Qian , Li Benhua , Luan Tiankuo , Wang Xiaoyu , Duan Bixia , Wei Chengcheng , Chen Shi 
Published: March 2024

IntroductionSerological responses following hepatitis B vaccination are crucial for preventing hepatitis B (HBV). However, the potential relationship between serum lipid levels and immunity from HBV vaccination remains poorly understood.MethodsIn this study, we conducted an analysis of the National Health and Nutrition Examination Survey (NHANES) data spanning from 2003 to 2016. Multivariable weighted logistic regression models, generalized linear analysis, stratified models, smooth curve fitting, segmentation effect analysis and sensitivity analysis were utilized to assess the relationships.ResultsAfter adjusting for relevant covariates, we observed that low levels of high-density lipoprotein cholesterol (HDL) were independently linked to a significantly lower seroprotective rate. Compared to HDL levels of ≥ 60 mg/dL, the odds ratios (ORs) for individuals with borderline levels (40-59 mg/dL for men, 50-59 mg/dL for women) and low levels (&lt; 40 mg/dL for men, &lt; 50 mg/dL for women) were 0.83 (95% CI 0.69-0.99) and 0.65 (95% CI 0.56-0.78), respectively. This association was particularly pronounced in individuals aged 40 or older. Conversely, higher levels of the triglyceride to HDL (TG/HDL) ratio (OR, 0.90; 95% CI, 0.84-0.98), total cholesterol to HDL (Chol/HDL) ratio (OR, 0.77; 95% CI, 0.64-0.92), and low-density lipoprotein to HDL (LDL/HDL) ratio (OR, 0.85; 95% CI, 0.76-0.96) were associated with a decreased likelihood of seroprotection.ConclusionThis study suggests that lipid levels may play a role in modulating the immune response following HBV vaccination.
Mendelian randomization supports genetic liability to hospitalization for COVID-19 as a risk factor of pre-eclampsia
Authors: Wu Weizhen , Zhang Junning , Qiao Yizhuo , Ren Yuehan , Rao Xuezhi , Xu Zhijie , Liu Baoxing 
Published: March 2024

BackgroundPre-eclampsia and eclampsia are among the major threats to pregnant women and fetuses, but they can be mitigated by prevention and early screening. Existing observational research presents conflicting evidence regarding the causal effects of coronavirus disease 2019 (COVID-19) on pre-eclampsia risk. Through Mendelian randomization (MR), this study aims to investigate the causal effect of three COVID-19 severity phenotypes on the risk of pre-eclampsia and eclampsia to provide more rigorous evidence.MethodsTwo-sample MR was utilized to examine causal effects. Summary-level data from genome-wide association studies (GWAS) of individuals of European ancestry were acquired from the GWAS catalog and FinnGen databases. Single-nucleotide polymorphisms associated with COVID-19 traits at p &lt; 5 × −8 were obtained and pruned for linkage disequilibrium to generate instrumental variables for COVID-19. Inverse variance weighted estimates were used as the primary MR results, with weighted median and MR-Egger as auxiliary analyses. The robustness of the MR findings was also evaluated through sensitivity analyses. Bonferroni correction was applied to primary results, with a p &lt; 0.0083 considered significant evidence and a p within 0.083–0.05 considered suggestive evidence.ResultsCritical ill COVID-19 [defined as hospitalization for COVID-19 with either a death outcome or respiratory support, OR (95% CI): 1.17 (1.03–1.33), p = 0.020] and hospitalized COVID-19 [defined as hospitalization for COVID-19, OR (95% CI): 1.10 (1.01–1.19), p = 0.026] demonstrated suggestive causal effects on pre-eclampsia, while general severe acute respiratory syndrome coronavirus 2 infection did not exhibit a significant causal effect on pre-eclampsia. None of the three COVID-19 severity phenotypes exhibited a significant causal effect on eclampsia.ConclusionsOur investigation demonstrates a suggestive causal effect of genetic susceptibility to critical ill COVID-19 and hospitalized COVID-19 on pre-eclampsia. The COVID-19 severity exhibited a suggestive positive dose–response relationship with the risk of pre-eclampsia. Augmented attention should be paid to pregnant women hospitalized for COVID-19, especially those needing respiratory support.
Case report of belt electrode-skeletal muscle electrical stimulation for acute heart failure with severe obesity: a novel therapeutic option for acute phase rehabilitation
Authors: Mochizuki Yuto , Jimba Takahiro , Yasukawa Syota , Katsura Aritomo , Fukuda Akira , Ando Jiro 
Published: March 2024

BackgroundBelt electrode skeletal muscle electrical stimulation (B-SES) is an emerging therapy anticipated to yield more favorable outcomes than conventional neuromuscular electrical stimulation (NMES), owing to its larger stimulation area. However, information on its efficacy and safety in patients with heart failure remains limited.Case presentationA 43-year-old man with a body mass index of 41 kg/m2 was admitted to our hospital for acute heart failure due to dilated cardiomyopathy. The patient required prolonged catecholamine support owing to poor cardiac function, and heart transplantation was considered. We initiated a mobilization program, but the patient's mobility was highly limited due to severe obesity and symptomatic orthostatic hypotension. B-SES was introduced to accomplish weight loss and early ambulation. We applied an intensive monitoring program for safe use and modulated the intensity of B-SES according to physical function. During the B-SES program, the patient's body weight decreased from 89.6 kg to 78.6 kg. Sequential evaluations of body composition and skeletal muscle ultrasonography revealed improved muscle mass, quality, and physical function. Furthermore, we explored the workload of B-SES using expiratory gas analysis. No adverse events were observed during B-SES.DiscussionWe successfully used B-SES to improve muscle function and morbidity in the treatment of acute heart failure. B-SES could be an option for patients with heart failure who have limited mobility and obesity.
Association of the metabolic score for insulin resistance with cardiovascular diseases, cardiovascular and all-cause mortality in Chinese hypertensive population
Authors: Zhang Liting , Yu Chao , Wang Tao , Zhou Wei , Bao Huihui , Cheng Xiaoshu 
Published: March 2024

ImportanceLittle is known about the relationship between the metabolic score for insulin resistance (METS-IR) and the prognosis of hypertensive patients in China.ObjectiveTo investigate the association between the novel non–insulin‐based METS-IR index and the cardiovascular composite endpoints and all-cause mortality in Chinese hypertensive participants.Design, setting, and participantsThis cohort study used data from the China H-Type Hypertension Project, a long-term prospective cohort consisting of 14234 hypertensive patients in southern China, with a baseline from March to August 2018. The median follow-up period for participants was 3.94 years, as of 2022. The data analysis period is from July 2023 to September 2023.ExposuresMETS-IR index of participants in the Chinese H-type hypertension project. The calculation formula for METS-IR is (Ln (2 × FPG) +TG) × BMI/Ln (HDL-C).Main outcomes and measuresCardiovascular events and cardiovascular, all-cause mortality were identified by linking the cohort database with the health care system through October, 2023.ResultsA total of 14220 participants were included in this study. The prevalence rates of cardiovascular disease (CVD), cardiovascular death, and all-cause death were 2.59% (369/14220), 2.79% (397/14220), and 5.66% (805/14220), respectively. After adjusting for confounding factors in the multivariate logistic regression analysis models, the METS-IR index was significantly positively correlated with CVD, and cardiovascular, all-cause mortality, whether as a categorical or continuous variable. Layered analysis showed that the METS-IR index of hypertensive participants in different subgroups was positively correlated with the endpoint event.Conclusions and relevanceThis large, prospective cohort study demonstrated that the METS-IR index, a new IR evaluation index, were independently associated with a higher risk of the cardiovascular composite endpoint and all-cause mortality among Chinese hypertensive population. Importantly, our finding provides an independent indicator for evaluating the prognosis of hypertensive patients.
Expression and clinical value of CXCR4 in high grade gastroenteropancreatic neuroendocrine neoplasms
Authors: Pang Chaoyu , Li Yongzheng , Shi Ming , Fan Zhiyao , Gao Xin , Meng Yufan , Liu Shujie , Gao Changhao , Su Peng , Wang Xiao , Zhan Hanxiang 
Published: March 2024

BackgroundCXC chemokine receptor 4 (CXCR4) is associated with the progression and metastasis of numerous malignant tumors. However, its relationship with Gastroenteropancreatic Neuroendocrine Neoplasms Grade 3 (GEP-NENs G3) is unclear. The aim of this study was to characterize the expression of CXCR4 in GEP-NENS and to explore the clinical and prognostic value of CXCR4.MethodsThis study retrospectively collected clinical and pathological data from patients with GEP-NENs who receiving surgery in Qilu Hospital of Shandong University from January 2013 to April 2021, and obtained the overall survival of the patients based on follow-up. Immunohistochemistry (IHC) was performed on pathological paraffin sections to observe CXCR4 staining. Groups were made according to pathological findings. Kaplan-Meier (K-M) curve was used to evaluate prognosis. SPSS 26.0 was used for statistical analysis.Results100 GEP-NENs G3 patients were enrolled in this study. There was a significant difference in primary sites (P=0.002), Ki-67 index (P&lt;0.001), and Carcinoembryonic Antigen (CEA) elevation (P=0.008) between neuroendocrine tumor (NET) G3 and neuroendocrine carcinoma (NEC). CXCR4 was highly expressed only in tumors, low or no expressed in adjacent tissues (P&lt;0.001). The expression level of CXCR4 in NEC was significantly higher than that in NET G3 (P=0.038). The K-M curves showed that there was no significant difference in overall survival between patients with high CXCR4 expression and patients with low CXCR4 expression, either in GEP-NEN G3 or NEC (P=0.920, P=0.842. respectively).ConclusionDifferential expression of CXCR4 was found between tumor and adjacent tissues and between NET G3 and NEC. Our results demonstrated that CXCR4 can be served as a new IHC diagnostic indicator in the diagnosis and differential diagnosis of GEP-NENs G3. Further studies with multi-center, large sample size and longer follow-up are needed to confirm the correlation between CXCR4 expression level and prognosis.
Neurodevelopmental disorders as a risk factor for temporomandibular disorder: evidence from Mendelian randomization studies
Authors: Wu Xueqiang , Li Zefang , Cui Yiping , Yan Zhaojun , Lu Tingting , Cui Song 
Published: March 2024

Objective: This study aims to clarify the incidence rate of temporomandibular joint disease in patients with mental disorders.Methods: Data extracted from the Psychiatric Genomics Consortium and FinnGen databases employed the Mendelian Randomization (MR) method to assess the associations of three neurodevelopmental disorders (NDDs)—Attention-Deficit/Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), and Tourette’s Disorder (TD)—as exposure factors with Temporomandibular Disorder (TMD). The analysis used a two-sample MR design, employing the Inverse Variance Weighted (IVW) method to evaluate the relationships between these disorders and Temporomandibular Disorder. Sensitivity analysis and heterogeneity assessments were conducted. Potential confounding factors like low birth weight, childhood obesity, and body mass index were controlled for.Results: The study found that ADHD significantly increased the risks for TMD (OR = 1.2342, 95%CI (1.1448–1.3307), p &lt; 0.00001), TMD (including avohilmo) (OR = 1.1244, 95%CI (1.0643–1.1880), p = 0.00003), TMD-related pain (OR = 1.1590, 95%CI (1.0964–1.2252), p &lt; 0.00001), and TMD-related muscular pain associated with fibromyalgia (OR = 1.1815, 95%CI (1.1133–1.2538), p &lt; 0.00001), while other disorders did not show significant causal relationships.Conclusion: This study reveals the elevated risk of various TMD aspects due to ADHD. Furthermore, we discuss the link between low vitamin D levels ADHD and TMD. Future research should address these limitations and delve further into the complex interactions between ADHD, ASD, TD, and TMD.
Distinct functional neutrophil phenotypes in sepsis patients correlate with disease severity
Authors: Yang Qingliang , Langston Jordan C. , Prosniak Roman , Pettigrew Samantha , Zhao Huaqing , Perez Edwin , Edelmann Hannah , Mansoor Nadia , Merali Carmen , Merali Salim , Marchetti Nathaniel , Prabhakarpandian Balabhaskar , Kiani Mohammad F. , Kilpatrick Laurie E. 
Published: March 2024

PurposeSepsis is a clinical syndrome defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis is a highly heterogeneous syndrome with distinct phenotypes that impact immune function and response to infection. To develop targeted therapeutics, immunophenotyping is needed to identify distinct functional phenotypes of immune cells. In this study, we utilized our Organ-on-Chip assay to categorize sepsis patients into distinct phenotypes using patient data, neutrophil functional analysis, and proteomics.MethodsFollowing informed consent, neutrophils and plasma were isolated from sepsis patients in the Temple University Hospital ICU (n=45) and healthy control donors (n=7). Human lung microvascular endothelial cells (HLMVEC) were cultured in the Organ-on-Chip and treated with buffer or cytomix ((TNF/IL-1β/IFNγ). Neutrophil adhesion and migration across HLMVEC in the Organ-on-Chip were used to categorize functional neutrophil phenotypes. Quantitative label-free global proteomics was performed on neutrophils to identify differentially expressed proteins. Plasma levels of sepsis biomarkers and neutrophil extracellular traps (NETs) were determined by ELISA.ResultsWe identified three functional phenotypes in critically ill ICU sepsis patients based on ex vivo neutrophil adhesion and migration patterns. The phenotypes were classified as: Hyperimmune characterized by enhanced neutrophil adhesion and migration, Hypoimmune that was unresponsive to stimulation, and Hybrid with increased adhesion but blunted migration. These functional phenotypes were associated with distinct proteomic signatures and differentiated sepsis patients by important clinical parameters related to disease severity. The Hyperimmune group demonstrated higher oxygen requirements, increased mechanical ventilation, and longer ICU length of stay compared to the Hypoimmune and Hybrid groups. Patients with the Hyperimmune neutrophil phenotype had significantly increased circulating neutrophils and elevated plasma levels NETs.ConclusionNeutrophils and NETs play a critical role in vascular barrier dysfunction in sepsis and elevated NETs may be a key biomarker identifying the Hyperimmune group. Our results establish significant associations between specific neutrophil functional phenotypes and disease severity and identify important functional parameters in sepsis pathophysiology that may provide a new approach to classify sepsis patients for specific therapeutic interventions.
Long noncoding RNAs and circular RNAs as potential diagnostic biomarkers of inflammatory bowel diseases: a systematic review and meta-analysis
Authors: Belete Melaku Ashagrie , Tadesse Selamyhun , Tilahun Mihret , Gedefie Alemu , Shibabaw Agumas , Mulatie Zewudu , Wudu Muluken Amare , Gebremichael Saba , Debash Habtu , Alebachew Mihreteab , Alemayehu Ermiyas 
Published: March 2024

IntroductionInflammatory bowel disease (IBD) poses a growing global burden, necessitating the discovery of reliable biomarkers for early diagnosis. The clinical significance of dysregulated expression of long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) in diagnosing IBD has not been well established. Thus, our study aimed to investigate the diagnostic value of lncRNAs and circRNAs for IBD based on currently available studies.MethodsA comprehensive search was carried out in diverse electronic databases, such as PubMed, Embase, Scopus, Science Direct and Wiley Online Library to retrieve articles published until October 30, 2023. Stata 17.0 software was employed to determine pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic ratio (DOR), and area under the curve (AUC). Heterogeneity, subgroup analysis, and meta-regression were explored, and publication bias was assessed using Deeks’ funnel plot. Fagan’s nomogram and likelihood ratio scattergram were employed to evaluate the clinical validity.ResultA total of 11 articles encompassing 21 studies which involved 1239 IBD patients and 985 healthy controls were investigated. The findings revealed lncRNAs exhibit high level of pooled sensitivity 0.94 (95% CI: 0.87-0.97) and specificity 0.99 (95% CI: 0.89-1.00), along with PLR, NLR, DOR, and AUC values of 64.25 (95% CI: 7.39-558.66), 0.06 (95% CI: 0.03-0.13), 1055.25 (95% CI: 70.61-15770.77), and 0.99 (95% CI: 0.97-0.99), respectively. Conversely, CircRNAs showed moderate accuracy in IBD diagnosis, with sensitivity of 0.68 (95% CI: 0.61-0.73), specificity of 0.73 (95% CI: 0.65-0.79), PLR of 2.47 (95% CI: 1.94-3.16), NLR of 0.45 (95% CI: 0.38-0.53), DOR of 5.54 (95% CI: 3.88-7.93), and AUC value of 0.75 (95% CI: 0.71-0.79). Moreover, findings from subgroup analysis depicted heightened diagnostic efficacy when employing lncRNA H19 and a large sample size (≥100), with notable efficacy in diagnosing both ulcerative colitis (UC) and Crohn’s disease (CD).ConclusionLncRNAs exhibit high diagnostic accuracy in distinguishing patients with IBD from healthy controls signifying their possible use as potential biomarkers, while circRNAs showed moderate diagnostic accuracy. Nevertheless, to validate our findings and confirm the clinical utility of lncRNAs and circRNAs in IBD diagnosis, a large pool of prospective and multi-center studies should be undertaken.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42023491840.
Autoimmune and neuropsychiatric phenotypes in a Mecp2 transgenic mouse model on C57BL/6 background
Authors: Li Yaxi , Zhang Shu , Tang Chenling , Yang Bowen , Atrooz Fatin , Ren Zhifeng , Mohan Chandra , Salim Samina , Wu Tianfu 
Published: March 2024

IntroductionSystemic Lupus Erythematosus (SLE) impacts the central nervous system (CNS), leading to severe neurological and psychiatric manifestations known as neuropsychiatric lupus (NPSLE). The complexity and heterogeneity of clinical presentations of NPSLE impede direct investigation of disease etiology in patients. The limitations of existing mouse models developed for NPSLE obstruct a comprehensive understanding of this disease. Hence, the identification of a robust mouse model of NPSLE is desirable.MethodsC57BL/6 mice transgenic for human MeCP2 (B6.Mecp2Tg1) were phenotyped, including autoantibody profiling through antigen array, analysis of cellularity and activation of splenic immune cells through flow cytometry, and measurement of proteinuria. Behavioral tests were conducted to explore their neuropsychiatric functions. Immunofluorescence analyses were used to reveal altered neurogenesis and brain inflammation. Various signaling molecules implicated in lupus pathogenesis were examined using western blotting.ResultsB6.Mecp2Tg1 exhibits elevated proteinuria and an overall increase in autoantibodies, particularly in female B6.Mecp2Tg1 mice. An increase in CD3+CD4+ T cells in the transgenic mice was observed, along with activated germinal center cells and activated CD11b+F4/80+ macrophages. Moreover, the transgenic mice displayed reduced locomotor activity, heightened anxiety and depression, and impaired short-term memory. Immunofluorescence analysis revealed IgG deposition and immune cell infiltration in the kidneys and brains of transgenic mice, as well as altered neurogenesis, activated microglia, and compromised blood-brain barrier (BBB). Additionally, protein levels of various key signaling molecules were found to be differentially modulated upon MeCP2 overexpression, including GFAP, BDNF, Albumin, NCoR1, mTOR, and NLRP3.DiscussionCollectively, this work demonstrates that B6.Mecp2Tg1 mice exhibit lupus-like phenotypes as well as robust CNS dysfunctions, suggesting its utility as a new animal model for NPSLE.
Identification of bacteria and fungi responsible for litter decomposition in desert steppes via combined DNA stable isotope probing
Authors: Ye He , Tu Nare , Wu Zhendan , He Shilong , Zhao Yu , Yue Mei , Hong Mei 
Published: March 2024

IntroductionSoil microorganisms play crucial roles in determining the fate of litter in desert steppes because their activities constitute a major component of the global carbon (C) cycle. Human activities lead to increased ecosystem nitrogen (N) deposition, which has unpredictable impacts on soil microorganism diversity and functions. Nowadays, it is necessary to further study the succession of these microorganisms in the process of litter decomposition in desert steppe, and explore the effect of N deposition on this process. This issue is particularly important to resolve because it contributes to the broader understanding of nutrient cycling processes in desert steppes.MethodsIn this study, DNA stable isotope probing (DNA-SIP) was used to study changes in soil bacterial and fungal community composition and function during 8 weeks of culture of 13C-labeled litter in desert steppes.ResultsThe results were as follows: (1) Actinomycetota, Pseudomonadota, and Ascomycota are the main microorganisms involved in litter decomposition in desert steppes; (2) N deposition (50 kg ha−1 year−1) significantly increased the relative abundance of some microorganisms involved in the decomposition process; and (3) N deposition likely promotes litter decomposition in desert steppes by increasing the abundances of N cycles bacteria (usually carrying GH family functional genes).DiscussionThese findings contribute to a deeper understanding of the C assimilation mechanisms associated with litter residue production, emphasizing the importance of extensive C utilization.