bluuebunny/crossref_metadata_2025_split huggingface dataset:
First evidence of schmallenberg virus infection in southern Italy
Authors: Ferrara Gianmarco , Wernike Kerstin , Iovane Giuseppe , Pagnini Ugo , Montagnaro Serena 
Published: July 2023

Abstract
Background
Schmallenberg virus (SBV) is a vector-borne pathogen that mainly affects ruminants. Schmallenberg disease has never been described in southern Italy, although this geographic area displays climatic features suitable for Culicoides biting midges, which transmit the pathogen. An observational study was carried out in the Campania region in 2020 to evaluate the seroprevalence in cattle and water buffalo as well as to identify the risk factors involved in the distribution of SBV.

Results
Relatively high seroprevalences of 38.2% (cattle) and 43% (water buffalo) were found by using a commercial SBV ELISA, which is comparable to the prevalence obtained in other countries under post-epidemic conditions. A virus neutralization assay performed on positive samples showed high titers in a large percentage of animals which is assumed to indicate recent exposure. Bivariate analysis of several variables revealed some environmental factors associated with higher seroprevalence, such as mean annual temperature, distance from the coast, and altitude. Multivariate logistic regression confirmed the statistical association only for mean annual temperature, that was found to be the main factor responsible for the distribution of the virus in southern Italy. In addition, molecular diagnosis attempts were performed on serum samples and resulted in the detection of SBV RNA in two herds and six animals.

Conclusions
In this work we have demonstrated the circulation of SBV in southern Italy using both molecular and serological assays. This study emphasized the essential role of monitoring in preventing the re-emergence of vector-borne diseases in ruminants.
Association of sodium-glucose cotransporter 2 inhibitors with post-discharge outcomes in patients with acute heart failure with type 2 diabetes: a cohort study
Authors: Park Sohee , Jeong Han Eol , Lee Hyesung , You Seng Chan , Shin Ju-Young 
Published: July 2023

AbstractBackgroundGiven the cumulative evidence on the effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2is) on chronic heart failure, demand is emerging for further information on their effects in patients who are hospitalized for acute heart failure. However, there is still limited evidence about the class effect of SGLT2is on acute heart failure. We investigated whether initiating treatment with SGLT2is after an episode of acute heart failure reduces the risks of post-discharge heart failure readmission or cardiovascular mortality among patients with type 2 diabetes.MethodsA retrospective cohort study was conducted in a cohort of patients with type 2 diabetes who hospitalized for heart failure, using Korean Health Insurance Review & Assessment database (2015–2020). The exposure was defined as initiation of SGLT2is during hospitalization or at discharge. We assessed hazards of post-discharge heart failure readmission and cardiovascular death at 1-year, and 30-, 60-, and 90-day from the date of discharge in the SGLT2is users and non-users. Cox proportional hazards models with propensity score-based inverse probability of treatment weighting were used to estimate hazard ratios and 95% confidence intervals.ResultsAmong 56,343 patients with type 2 diabetes hospitalized for heart failure, 29,290 patients were included in the study cohort (mean [SD] age, 74.1 [10.8] years; 56.1% women); 818 patients (2.8%) were prescribed SGLT2is during index hospitalization or at discharge. Patients with a prescription for SGLT2i vs. those without prescription had lower rates of heart failure readmission or cardiovascular death at 1 year (22.4% vs. 25.3%; adjusted hazard ratio, 0.90 [95% confidence interval, 0.87–0.93]), and also at 30 days (7.0% vs. 7.7%%; 0.74 [0.69–0.79]).ConclusionsAmong patients with type 2 diabetes, initiating SGLT2i treatment after an episode of acute heart failure was significantly associated with a reduced combined risk of heart failure readmission and cardiovascular mortality in a nationwide cohort reflecting routine clinical practice.
Inequalities in the burden of non-communicable diseases across European countries: a systematic analysis of the Global Burden of Disease 2019 study
Authors: Andrade Carlos Alexandre Soares , Mahrouseh Nour , Gabrani Jonila , Charalampous Periklis , Cuschieri Sarah , Grad Diana Alecsandra , Unim Brigid , Mechili Enkeleint A. , Chen-Xu José , Devleesschauwer Brecht , Isola Gaetano , von der Lippe Elena , Baravelli Carl Michael , Fischer Florian , Weye Nanna , Balaj Mirza , Haneef Romana , Economou Mary , Haagsma Juanita A. , Varga Orsolya 
Published: July 2023

Abstract
Background
Although overall health status in the last decades improved, health inequalities due to non-communicable diseases (NCDs) persist between and within European countries. There is a lack of studies giving insights into health inequalities related to NCDs in the European Economic Area (EEA) countries. Therefore, the aim of the present study was to quantify health inequalities in age-standardized disability adjusted life years (DALY) rates for NCDs overall and 12 specific NCDs across 30 EEA countries between 1990 and 2019. Also, this study aimed to determine trends in health inequalities and to identify those NCDs where the inequalities were the highest.

Methods
DALY rate ratios were calculated to determine and compare inequalities between the 30 EEA countries, by sex, and across time. Annual rate of change was used to determine the differences in DALY rate between 1990 and 2019 for males and females. The Gini Coefficient (GC) was used to measure the DALY rate inequalities across countries, and the Slope Index of Inequality (SII) to estimate the average absolute difference in DALY rate across countries.

Results
Between 1990 and 2019, there was an overall declining trend in DALY rate, with larger declines among females compared to males. Among EEA countries, in 2019 the highest NCD DALY rate for both sexes were observed for Bulgaria. For the whole period, the highest DALY rate ratios were identified for digestive diseases, diabetes and kidney diseases, substance use disorders, cardiovascular diseases (CVD), and chronic respiratory diseases – representing the highest inequality between countries. In 2019, the highest DALY rate ratio was found between Bulgaria and Iceland for males. GC and SII indicated that the highest inequalities were due to CVD for most of the study period – however, overall levels of inequality were low.

Conclusions
The inequality in level 1 NCDs DALYs rate is relatively low among all the countries. CVDs, digestive diseases, diabetes and kidney diseases, substance use disorders, and chronic respiratory diseases are the NCDs that exhibit higher levels of inequality across countries in the EEA. This might be mitigated by applying tailored preventive measures and enabling healthcare access.
Evaluation of multiple biological indicators for the combined diagnosis of metastases from colorectal cancer—a retrospective study based on 1163 patients
Authors: Chen Bangquan , Zhou Jiajie , Ma Yue , Sun Qiannan , Ren Jun , Wang Daorong 
Published: July 2023

Abstract
Objective
This study aimed to investigate the efficacy of inflammatory markers (NLR, PLR) combined with tumor markers (CA50, CA199, CEA) in the diagnosis of colorectal cancer metastasis by a single-center retrospective study.

Methods
A total of 1163 CRC patients who received treatments in our hospital from January 2017 to December 2021 were enrolled retrospectively. Patients were grouped according to the absence of metastasis. The separate efficacy of tumor markers, NLR and PLR, was evaluated in the diagnosis of metastasis of colorectal cancer using ROC curve analysis, and their optimal cut-off values for distant metastases from colorectal cancer were determined. The area under the ROC curve (AUC) of the tumor markers combined with NLR and PLR was calculated by binary logistic regression analysis to evaluate the diagnostic efficacy of metastasis of colorectal cancer. In addition, patients were divided into two groups of high and low levels according to the optimal cut-off values, and the effects of NLR, PLR, and tumor markers on distant metastasis of colorectal cancer were evaluated using multiple logistic regression analysis.

Result
The abnormal rate of CA50, CA199, CEA, NLR, and PLR in two subgroupsIt was statistically significant (P < 0.05). After AUC testifying, the diagnostic efficacy of NLR and PLR was equivalent to that of tumor marker (P > 0.05). In assessment of liver metastasis, peritoneal metastasis, and multiple metastasis, AUC of NLR and PLR with CRC-specific tumor markers showed higher predictive efficacy than AUC without combined NLR nor PLR. The CA50, CA199, CEA, PLR, and NLR were proved independently associated with metastasis using multiple logistic regression analysis (P < 0.05).

Conclusion
NLR and PLR are noted tumor markers of colorectal cancer, which are characterized by noninvasive, high diagnostic efficacy, easy availability, and low cost. They can be combined with traditional tumor markers to evaluate and diagnose colorectal cancer metastasis by clinicians.
Quality of vital event data for infant mortality estimation in prospective, population-based studies: an analysis of secondary data from Asia, Africa, and Latin America
Authors: Erchick Daniel J. , Subedi Seema , Verhulst Andrea , Guillot Michel , Adair Linda S. , Barros Aluísio J. D. , Chasekwa Bernard , Christian Parul , da Silva Bruna Gonçalves C. , Silveira Mariângela F. , Hallal Pedro C. , Humphrey Jean H. , Huybregts Lieven , Kariuki Simon , Khatry Subarna K. , Lachat Carl , Matijasevich Alicia , McElroy Peter D. , Menezes Ana Maria B. , Mullany Luke C. , Perez Tita Lorna L. , Phillips-Howard Penelope A. , Roberfroid Dominique , Santos Iná S. , ter Kuile Feiko O. , Ravilla Thulasiraj D. , Tielsch James M. , Wu Lee S. F. , Katz Joanne 
Published: July 2023

Abstract
Introduction
Infant and neonatal mortality estimates are typically derived from retrospective birth histories collected through surveys in countries with unreliable civil registration and vital statistics systems. Yet such data are subject to biases, including under-reporting of deaths and age misreporting, which impact mortality estimates. Prospective population-based cohort studies are an underutilized data source for mortality estimation that may offer strengths that avoid biases.

Methods
We conducted a secondary analysis of data from the Child Health Epidemiology Reference Group, including 11 population-based pregnancy or birth cohort studies, to evaluate the appropriateness of vital event data for mortality estimation. Analyses were descriptive, summarizing study designs, populations, protocols, and internal checks to assess their impact on data quality. We calculated infant and neonatal morality rates and compared patterns with Demographic and Health Survey (DHS) data.

Results
Studies yielded 71,760 pregnant women and 85,095 live births. Specific field protocols, especially pregnancy enrollment, limited exclusion criteria, and frequent follow-up visits after delivery, led to higher birth outcome ascertainment and fewer missing deaths. Most studies had low follow-up loss in pregnancy and the first month with little evidence of date heaping. Among studies in Asia and Latin America, neonatal mortality rates (NMR) were similar to DHS, while several studies in Sub-Saharan Africa had lower NMRs than DHS. Infant mortality varied by study and region between sources.

Conclusions
Prospective, population-based cohort studies following rigorous protocols can yield high-quality vital event data to improve characterization of detailed mortality patterns of infants in low- and middle-income countries, especially in the early neonatal period where mortality risk is highest and changes rapidly.
Practical dietary interventions to prevent cardiovascular disease suitable for implementation in primary care: an ADAPTE-guided systematic review of international clinical guidelines
Authors: Le Goff Delphine , Aerts Naomi , Odorico Michele , Guillou-Landreat Morgane , Perraud Gabriel , Bastiaens Hilde , Musinguzi Geofrey , Le Reste Jean-Yves , Barais Marie 
Published: July 2023

Abstract
Purpose
Cardiovascular diseases (CVD) are the leading cause of death globally. The current model of care for high-income countries involves preventive medication and highly trained healthcare professionals, which is expensive and not transposable to low-income countries. An innovative, effective approach adapted to limited human, technical, and financial resources is required. Measures to reduce CVD risk factors, including diet, are proven to be effective. The survey “Scaling-up Packages of Interventions for Cardiovascular disease prevention in selected sites in Europe and Sub-Saharan Africa” aims to develop non-pharmacological cardiovascular prevention and control programs in primary care and community settings in high, middle, and low-income countries. This review aims to identify the existing, validated dietary interventions for primary CVD prevention from national and international clinical guidelines that can be implemented in primary care and communities.

Methods
A systematic review of CVD prevention guidelines was conducted between September 2017 and March 2023 using the Turning Research Into Practice medical database, the Guidelines International Network, and a purposive search. The ADAPTE procedure was followed. Two researchers independently conducted the searches and appraisals. Guidelines published after 01/01/2012 addressing non-pharmacological, dietary interventions for primary CVD prevention or CVD risk factor management, in the adult general population in primary care or in community settings were included and appraised using the Appraisal of Guidelines Research and Evaluation II score. Individual dietary recommendations and the studies supporting them were extracted. Then supporting data about each specific dietary intervention were extracted into a matrix.

Results
In total, 1375 guidelines were identified, of which 39 were included. From these, 383 recommendations, covering 10 CVD prevention themes were identified. From these recommendations, 165 studies for effective dietary interventions for CVD prevention were found. Among these, the DASH diet was the most effective on multiple CVD risk factors. Combining diet with other interventions such as exercise and smoking cessation increased efficacy. No guidelines provided detailed implementation strategies.

Conclusion
The DASH diet combined with other interventions was the most effective on an individual basis. However, expansion in the wider population seems difficult, without government support to implement regulations such as reducing salt content in processed food.

Trial Registration
Clinical Trials NCT03886064
Hsa_circ_0002348 regulates trophoblast proliferation and apoptosis through miR-126-3p/BAK1 axis in preeclampsia
Authors: Zhou Jizi , Zhao Ying , An Ping , Zhao Huanqiang , Li Xiaotian , Xiong Yu 
Published: July 2023

Abstract
Background
Preeclampsia is a common pregnancy complication characterized by high blood pressure and damage to organs. Abnormal placenta and vascular function can lead to preeclampsia. Accumulating evidence has suggested a potential link between circular RNAs (circRNAs) and preeclampsia. As a placenta and endothelial-expressed circRNA, hsa_circ_0002348, may be promising to be the novel molecular target for preeclampsia. However, the function and mechanism of hsa_circ_0002348 in preeclampsia has not been elucidated.

Materials and methods
An overlap analysis of two circRNA profiles from placenta and endothelial cells was used to identify a functionally unknown circRNA, hsa_circ_0002348. Quantitative real-time PCR (qRT-PCR) and in situ hybridization (ISH) were used to detect its expression in the trophoblast cells and placental tissues. The mouse model of lipopolysaccharide (LPS)-induced preeclampsia was established to determine the in vivo role of hsa_circ_0002348. RNA immunoprecipitation (RIP), Luciferase reporter assay, qRT-PCR, western blot, gain- and loss-of-function and rescue experiments were conducted to uncover the role of hsa_circ_0002348 and its interaction with miR-126-3p and BAK1 in regulating trophoblast proliferation and apoptosis. Fluorescence in situ hybridization (FISH) and Immunohistochemistry (IHC) were performed to examine the expression of miR-126-3p and BAK1 in mice and human placentas, respectively.

Results
Hsa_circ_0002348 was significantly increased in the preeclampsia placentas, and positively correlated with the severity of preeclampsia patients’ clinical manifestations. Its overexpression exacerbated preeclampsia-like features in the mouse model of LPS-induced preeclampsia. Functionally, hsa_circ_0002348 was found to inhibit trophoblast proliferation and promote trophoblast apoptosis. Mechanistically, hsa_circ_0002348, as an endogenous miR-126-3p sponge, upregulated the expression of BAK1. Additionally, both hsa_circ_0002348 knockdown and miR-126-3p overexpression enhanced the mammalian target of rapamycin (mTOR) and ERK1/2 signaling pathway.

Conclusions
Hsa_circ_0002348 might be a novel regulator of trophoblast proliferation and apoptosis through miR-126-3p/BAK1 axis in preeclampsia, which may serve as a potential target for detecting and treating preeclampsia.
Mitochondrial metabolic dysfunction and non-alcoholic fatty liver disease: new insights from pathogenic mechanisms to clinically targeted therapy
Authors: Zheng Youwei , Wang Shiting , Wu Jialiang , Wang Yong 
Published: July 2023

AbstractMetabolic dysfunction-associated fatty liver disease (MAFLD) is among the most widespread metabolic disease globally, and its associated complications including insulin resistance and diabetes have become threatening conditions for human health. Previous studies on non-alcoholic fatty liver disease (NAFLD) were focused on the liver’s lipid metabolism. However, growing evidence suggests that mitochondrial metabolism is involved in the pathogenesis of NAFLD to varying degrees in several ways, for instance in cellular division, oxidative stress, autophagy, and mitochondrial quality control. Ultimately, liver function gradually declines as a result of mitochondrial dysfunction. The liver is unable to transfer the excess lipid droplets outside the liver. Therefore, how to regulate hepatic mitochondrial function to treat NAFLD has become the focus of current research. This review provides details about the intrinsic link of NAFLD with mitochondrial metabolism and the mechanisms by which mitochondrial dysfunctions contribute to NAFLD progression. Given the crucial role of mitochondrial metabolism in NAFLD progression, the application potential of multiple mitochondrial function improvement modalities (including physical exercise, diabetic medications, small molecule agonists targeting Sirt3, and mitochondria-specific antioxidants) in the treatment of NAFLD was evaluated hoping to provide new insights into NAFLD treatment.
Discovery of therapeutic targets for spinal cord injury based on molecular mechanisms of axon regeneration after conditioning lesion
Authors: Wang Xiaoxiong , Li Wenxiang , Zhang Jianping , Li Jinze , Zhang Xianjin , Wang Min , Wei Zhijian , Feng Shiqing 
Published: July 2023

Abstract
Background
Preinjury of peripheral nerves triggers dorsal root ganglia (DRG) axon regeneration, a biological change that is more pronounced in young mice than in old mice, but the complex mechanism has not been clearly explained. Here, we aim to gain insight into the mechanisms of axon regeneration after conditioning lesion in different age groups of mice, thereby providing effective therapeutic targets for central nervous system (CNS) injury.

Methods
The microarray GSE58982 and GSE96051 were downloaded and analyzed to identify differentially expressed genes (DEGs). The protein–protein interaction (PPI) network, the miRNA-TF-target gene network, and the drug-hub gene network of conditioning lesion were constructed. The L4 and L5 DRGs, which were previously axotomized by the sciatic nerve conditioning lesions, were harvested for qRT-PCR. Furthermore, histological and behavioral tests were performed to assess the therapeutic effects of the candidate drug telmisartan in spinal cord injury (SCI).

Results
A total of 693 and 885 DEGs were screened in the old and young mice, respectively. Functional enrichment indicates that shared DEGs are involved in the inflammatory response, innate immune response, and ion transport. QRT-PCR results showed that in DRGs with preinjury of peripheral nerve, Timp1, P2ry6, Nckap1l, Csf1, Ccl9, Anxa1, and C3 were upregulated, while Agtr1a was downregulated. Based on the bioinformatics analysis of DRG after conditioning lesion, Agtr1a was selected as a potential therapeutic target for the SCI treatment. In vivo experiments showed that telmisartan promoted axonal regeneration after SCI by downregulating AGTR1 expression.

Conclusion
This study provides a comprehensive map of transcriptional changes that discriminate between young and old DRGs in response to injury. The hub genes and their related drugs that may affect the axonal regeneration program after conditioning lesion were identified. These findings revealed the speculative pathogenic mechanism involved in conditioning-dependent regenerative growth and may have translational significance for the development of CNS injury treatment in the future.
Identifying circRNA-associated-ceRNA networks in juvenile spondyloarthropathies patients
Authors: Qijiao Wei , Tao Zhang , Haimei Liu , Guomin Li , Li Sun 
Published: July 2023

Abstract
Background
Juvenile spondyloarthropathies (JSpA) are defined as a heterogeneous group of diseases that start before the age of 16. The study aimed to identify key genes and pathways that are influenced by circRNAs and to screen potential therapeutic agents for JSpA. The study involved the analysis of circRNA expression profiles, identification of circRNA-miRNA-mRNA regulatory networks, and functional annotation of differentially expressed genes. The results of the study may have provided insights into the molecular mechanisms underlying JSpA and potential therapeutic targets for this disease.

Methods
In this study, sequencing data of circRNA, miRNA, and mRNA were obtained from the GEO datasets. The data were then analyzed to identify candidates for constructing a circRNA-miRNA-mRNA network based on circRNA-miRNA interactions and miRNA-mRNA interactions. Functional enrichments of genes were performed using the DAVID database. A PPI network was constructed using the STRING database and visualized using Cytoscape software. The MCODE plugin app was used to explore hub genes in the PPI network. The expression changes in immune cells were assessed using the online CIBERSORT algorithm to obtain the proportion of various types of immune cells. Finally, the Connectivity Map L1000 platform was used to identify potential agents for JSpA treatment. Overall, this study aimed to provide a comprehensive understanding of the molecular mechanisms underlying JSpA and to identify potential therapeutic agents for this disease.

Results
A total of 225 differentially expressed circRNAs (DEcircRNAs), 23 differentially expressed miRNAs (DEmiRNAs) and 1324 differentially expressed mRNAs (DEmRNAs) were identified. We integrated 5 overlapped circRNAs, 7 miRNAs and 299 target mRNAs into a circRNA–miRNA–mRNA network. We next identified 10 hub genes based on the PPI network. KEGG pathway analysis revealed that the DEGs were mainly associated with JAK-STAT signal pathway. We found that neutrophils accounted for the majority of all enriched cells. In addition, we discovered several chemicals as potential treatment options for JSpA.

Conclusions
Through this bioinformatics analysis, we suggest a regulatory role for circRNAs in the pathogenesis and treatment of JSpA from the view of a competitive endogenous RNA (ceRNA) network.