bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differences in phenotypes, symptoms, and survival in patients with cardiomyopathy—a prospective observational study from the Sahlgrenska CardioMyoPathy Centre
Authors: Ljungman C. , Bollano E. , Rawshani A. , Nordberg Backelin C. , Dahlberg P. , Valeljung I. , Björkenstam M. , Hjalmarsson C. , Fu M. , Mellberg T. , Bartfay S.-E. , Polte C. L. , Andersson B. , Bergh N. 
Published: April 2023

IntroductionCardiomyopathy is the fourth most common cause of heart failure. The spectrum of cardiomyopathies may be impacted by changes in environmental factors and the prognosis may be influenced by modern treatment. The aim of this study is to create a prospective clinical cohort, the Sahlgrenska CardioMyoPathy Centre (SCMPC) study, and compare patients with cardiomyopathies in terms of phenotype, symptoms, and survival.MethodsThe SCMPC study was founded in 2018 by including patients with all types of suspected cardiomyopathies. This study included data on patient characteristics, background, family history, symptoms, diagnostic examinations, and treatment including heart transplantation and mechanical circulatory support (MCS). Patients were categorized by the type of cardiomyopathy on the basis of the diagnostic criteria laid down by the European Society of Cardiology (ESC) working group on myocardial and pericardial diseases. The primary outcomes were death, heart transplantation, or MCS, analyzed by Kaplan–Meier and Cox proportional regression, adjusted for age, gender, LVEF and QRS width on ECG in milliseconds.ResultsIn all, 461 patients and 73.1% men with a mean age of 53.6 ± 16 years were included in the study. The most common diagnosis was dilated cardiomyopathy (DCM), followed by cardiac sarcoidosis and myocarditis. Dyspnea was the most common initial symptom in patients with DCM and amyloidosis, while patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) presented with ventricular arrythmias. Patients with ARVC, left-ventricular non-compaction cardiomyopathy (LVNC), hypertrophic cardiomyopathy (HCM), and DCM had the longest time from the debut of symptoms until inclusion in the study. Overall, 86% of the patients survived without heart transplantation or MCS after 2.5 years. The primary outcome differed among the cardiomyopathies, where the worst prognosis was reported for ARVC, LVNC, and cardiac amyloidosis. In a Cox regression analysis, it was found that ARVC and LVNC were independently associated with an increased risk of death, heart transplantation, or MCS compared with DCM. Further, female gender, a lower LVEF, and a wider QRS width were associated with an increased risk of the primary outcome.ConclusionsThe SCMPC database offers a unique opportunity to explore the spectrum of cardiomyopathies over time. There is a large difference in characteristics and symptoms at debut and a remarkable difference in outcome, where the worst prognosis was reported for ARVC, LVNC, and cardiac amyloidosis.
Thermomechanical modelling of lithospheric slab tearing and its topographic response
Authors: Boonma Kittiphon , García-Castellanos Daniel , Jiménez-Munt Ivone , Gerya Taras 
Published: April 2023

Lithospheric slab tearing, the process by which a subducted lithospheric plate is torn apart and sinks into the Earth’s mantle, has been proposed as a cause for surface vertical motions in excess of 100 s of meters. However, little is known about the mechanisms that help initiate and control the propagation of slab tearing and the associated uplift. This study aims to explore these processes by means of 3D thermo-mechanical geodynamic modelling of a slab retreat oblique to a continental margin, using the Gibraltar Arc region (Betic Cordillera) as a scenario for inspiration. Our results suggest that the obliquity of the continental passive margin relative to the subduction trench leads to an asymmetric distribution of subduction forces and strength, facilitating the initiation of slab tearing. The model results predict a lateral migration of the tearing point at a velocity ranging between 38 and 68 cm/yr for a sublithospheric-mantle viscosity of up to 1e+22 Pa s. This fast slab tearing propagation yields uplift rates of 0.23–2.16 mm/yr above the areas where the subducted slab is torn apart, depending on mantle viscosity. Although a more detailed parametric exploration is needed, this range of uplift rates is compatible with the uplift rates required to overcome seaway erosion along the Atlantic-Mediterranean marine corridors during the Late Miocene, as proposed for the onset of the Messinian Salinity Crisis.
Immune-mediated inflammatory diseases and leukocyte telomere length: A Mendelian randomization study
Authors: Liu Meiling , Luo Ping , Liu Lihua , Wei Xianping , Bai Xue , Li Jicui , Wu Linlin , Luo Manyu 
Published: April 2023

Objective: To elucidate the potential causality of leukocyte telomere length (LTL) with immune-mediated inflammatory diseases (IMIDs), we conducted a Mendelian randomization (MR) study.Methods: The genetically predicted causation between LTL and IMIDs was evaluated using a two-sample MR method. We analyzed 16 major IMIDs, which included systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), ulcerative colitis (UC), Crohn’s disease (CD), ankylosing spondylitis (AS), sicca syndrome (SS), rheumatoid arthritis (RA), type 1 diabetes (T1D), primary sclerosing cholangitis (PSC), idiopathic pulmonary fibrosis (IPF), atopic dermatitis (AD), sarcoidosis, hypothyroidism, hyperthyroidism, psoriasis, and childhood asthma. The random-effects inverse-variance weighted (IVW) method was performed as the main analytical approach in MR. Various sensitivity analyses, including MR-Egger, MR robust adjusted profile score (MR-RAPS), weighted median, MR pleiotropy residual sum and outlier (MR-PRESSO) methods, weighted mode, radial plot, and radial regression, were used to guarantee the robustness of the results and detect horizontal pleiotropy. Cochran’s Q value was calculated to check for heterogeneity, and the MR Steiger approach was used to test the causal direction.Results: The MR results indicated significant inverse associations of LTL with risks of psoriasis (OR: 0.77, 95% CI: 0.66–0.89, and p = 3.66 × 10−4), SS (OR: 0.75, CI: 0.58–0.98, and p = 0.03), RA (OR: 0.77, 95% CI: 0.68–0.88, and p = 9.85 × 10−5), hypothyroidism (OR: 0.84, 95% CI: 0.78–0.91, and p = 7,08 × 10−6), hyperthyroidism (OR: 0.60, 95% CI: 0.44–0.83, and p = 1.90 × 10−3), sarcoidosis (OR: 0.67, 95% CI: 0.54–0.83, and p = 2.60 × 10−4), and IPF (OR: 0.41, 95% CI: 0.29–0.58, and p = 4.11 × 10−7) in the FinnGen study. We observed that longer LTL was associated with an increased risk of AS susceptibility (OR: 1.51, 95% CI: 1.18–1.94, and p = 9.66 × 10−4). The results of the IVW method showed no causal relationship between TL and SLE (OR: 0.92, 95% CI: 0.62–1.38, and p = 0.69) in the FinnGen study; however, a significantly positive correlation was shown between LTL and SLE in another larger GWAS (OR: 1.87, 95% CI: 1.37–2.54, and p = 8.01 × 10−5).Conclusion: Our findings reveal that abnormal LTL has the potential to increase the risk of IMIDs. Therefore, it could be treated as a predictor and may provide new potential treatment targets for IMIDs. However, the change of LTL may not be the direct cause of IMIDs. Further studies should aim at the pathogenic mechanism or potential protective effects of LTL in IMIDs.
Wiskott-Aldrich syndrome protein interacts and inhibits diacylglycerol kinase alpha promoting IL-2 induction
Authors: Velnati Suresh , Centonze Sara , Rossino Giulia , Purghè Beatrice , Antona Annamaria , Racca Luisa , Mula Sabrina , Ruffo Elisa , Malacarne Valeria , Malerba Mario , Manfredi Marcello , Graziani Andrea , Baldanzi Gianluca 
Published: April 2023

BackgroundPhosphorylation of diacylglycerol by diacylglycerol-kinases represents a major inhibitory event constraining T cell activation upon antigen engagement. Efficient TCR signalling requires the inhibition of the alpha isoform of diacylglycerol kinase, DGKα, by an unidentified signalling pathway triggered by the protein adaptor SAP. We previously demonstrated that, in SAP absence, excessive DGKα activity makes the T cells resistant to restimulation-induced cell death (RICD), an apoptotic program counteracting excessive T cell clonal expansion.ResultsHerein, we report that the Wiskott-Aldrich syndrome protein (WASp) inhibits DGKα through a specific interaction of the DGKα recoverin homology domain with the WH1 domain of WASp. Indeed, WASp is necessary and sufficient for DGKα inhibition, and this WASp function is independent of ARP2/3 activity. The adaptor protein NCK-1 and the small G protein CDC42 connect WASp-mediated DGKα inhibition to SAP and the TCR signalosome. In primary human T cells, this new signalling pathway is necessary for a full response in terms of IL-2 production, while minimally affecting TCR signalling and restimulation-induced cell death. Conversely, in T cells made resistant to RICD by SAP silencing, the enhanced DAG signalling due to DGKα inhibition is sufficient to restore apoptosis sensitivity.ConclusionWe discover a novel signalling pathway where, upon strong TCR activation, the complex between WASp and DGKα blocks DGKα activity, allowing a full cytokine response.
Integrated bioinformatic analysis of mitochondrial metabolism-related genes in acute myeloid leukemia
Authors: Tong Xiqin , Zhou Fuling 
Published: April 2023

BackgroundAcute myeloid leukemia (AML) is a common hematologic malignancy characterized by poor prognoses and high recurrence rates. Mitochondrial metabolism has been increasingly recognized to be crucial in tumor progression and treatment resistance. The purpose of this study was to examined the role of mitochondrial metabolism in the immune regulation and prognosis of AML.MethodsIn this study, mutation status of 31 mitochondrial metabolism-related genes (MMRGs) in AML were analyzed. Based on the expression of 31 MMRGs, mitochondrial metabolism scores (MMs) were calculated by single sample gene set enrichment analysis. Differential analysis and weighted co-expression network analysis were performed to identify module MMRGs. Next, univariate Cox regression and the least absolute and selection operator regression were used to select prognosis-associated MMRGs. A prognosis model was then constructed using multivariate Cox regression to calculate risk score. We validated the expression of key MMRGs in clinical specimens using immunohistochemistry (IHC). Then differential analysis was performed to identify differentially expressed genes (DEGs) between high- and low-risk groups. Functional enrichment, interaction networks, drug sensitivity, immune microenvironment, and immunotherapy analyses were also performed to explore the characteristic of DEGs.ResultsGiven the association of MMs with prognosis of AML patients, a prognosis model was constructed based on 5 MMRGs, which could accurately distinguish high-risk patients from low-risk patients in both training and validation datasets. IHC results showed that MMRGs were highly expressed in AML samples compared to normal samples. Additionally, the 38 DEGs were mainly related to mitochondrial metabolism, immune signaling, and multiple drug resistance pathways. In addition, high-risk patients with more immune-cell infiltration had higher Tumor Immune Dysfunction and Exclusion scores, indicating poor immunotherapy response. mRNA-drug interactions and drug sensitivity analyses were performed to explore potential druggable hub genes. Furthermore, we combined risk score with age and gender to construct a prognosis model, which could predict the prognosis of AML patients.ConclusionOur study provided a prognostic predictor for AML patients and revealed that mitochondrial metabolism is associated with immune regulation and drug resistant in AML, providing vital clues for immunotherapies.
FLAIR-hyperintense lesions in anti-MOG-associated encephalitis with seizures overlaying anti-N-methyl-D-aspartate receptor encephalitis: a case report and literature review
Authors: Yang Jia-Xin , Yang Miao-Miao , Han Yu-Juan , Gao Cai-Hong , Cao Jie 
Published: April 2023

BackgroundFLAIR-hyperintense lesions in anti-MOG-associated encephalitis with seizures (FLAMES) has been identified increasingly frequently in recent years. However, this rare MOG antibody disease may coexist with anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARe), in an overlap syndrome with unknown clinical features and prognosis.MethodsWe report a new case of this overlap syndrome and present a systematic review of similar cases in the literature to provide information on the clinical presentation, MRI features, EGG abnormalities, treatment, and prognosis of patients with this rare syndrome.ResultsA total of 12 patients were analyzed in the study. The most common clinical manifestations of FLAMES overlaid with anti-NMDARe were epilepsy (12/12), headache (11/12), and fever (10/12). Increases in intracranial pressure (median: 262.5 mmH2O, range: 150–380 mmH2O), cerebrospinal fluid (CSF) leukocyte count (median: 128×106/L, range: 1-610×106/L), and protein level (median: 0.48 g/L) were also observed. The median CSF anti-NMDAR antibody titer was 1:10 (1:1–1:32), while the median serum MOG antibody titer was 1:32 (1:10–1:1024). Seven cases exhibited unilateral cortical FLAIR hyperintensity, and five cases (42%) had bilateral cortical FLAIR hyperintensity, including four cases involving the bilateral medial frontal lobes. Of the 12 patients, five showed lesions at other sites (e.g., the brainstem, corpus callosum, or frontal orbital gyrus) before or after the development of cortical encephalitis. EEG showed slow waves in four cases, spike–slow waves in two cases, an epileptiform pattern in one case, and normal waves in two cases. The median number of relapses was two. Over a mean follow-up period of 18.5 months, only one patient experienced residual visual impairment, while the remaining 11 patients had good prognoses.ConclusionFLAMES alone is difficult to distinguish from overlap syndrome based on clinical features. However, FLAMES with bilateral medial frontal lobe involvement suggests the presence of the overlap syndrome.
The oral microbiome of patients with ischemic stroke predicts their severity and prognosis
Authors: Sun Wenbo , Huang Shengwen , Yang Xiaoli , Luo Yufan , Liu Luqiong , Wu Danhong 
Published: April 2023

Background and objectivesStroke is a common group of cerebrovascular diseases that can lead to brain damage or death. Several studies have shown a close link between oral health and stroke. However, the oral microbiome profiling of ischemic stroke (IS) and its potential clinical implication are unclear. This study aimed to describe the oral microbiota composition of IS, the high risk of IS, and healthy individuals and to profile the relationship between microbiota and IS prognosis.MethodsThis observational study recruited three groups: IS, high-risk IS (HRIS), and healthy control (HC) individuals. Clinical data and saliva were collected from participants. The modified Rankin scale score after 90 days was used to assess the prognosis of stroke. Extracted DNA from saliva and performed 16S ribosomal ribonucleic acid (rRNA) gene amplicon sequencing. Sequence data were analyzed using QIIME2 and R packages to evaluate the association between the oral microbiome and stroke.ResultsA total of 146 subjects were enrolled in this study according to the inclusion criteria. Compared with HC, HRIS and IS demonstrated a progressive increase trend in Chao1, observed species richness, and Shannon and Simpson diversity index. On the basis of permutational multivariate analysis of variance, the data indicate a great variation in the saliva microbiota composition between HC and HRIS (F = 2.40, P &lt; 0.001), HC and IS (F = 5.07, P &lt; 0.001), and HRIS and IS (F = 2.79, P &lt; 0.001). The relative abundance of g_Streptococcus, g_Prevotella, g_Veillonella, g_Fusobacterium, and g_Treponema was higher in HRIS and IS compared with that in HC. Furthermore, we constructed the predictive model by differential genera to effectively distinguish patients with IS with poor 90-day prognoses from those with good (area under the curve = 79.7%; 95% CI, 64.41%–94.97%; p &lt; 0.01).DiscussionIn summary, the oral salivary microbiome of HRIS and IS subjects have a higher diversity, and the differential bacteria have some predictive value for the severity and prognosis of IS. Oral microbiota may be used as potential biomarkers in patients with IS.
Knowledge-based engineering and computer vision for configuration-based substation design
Authors: Nordvall Erik , Wiberg Anton , Tarkian Mehdi 
Published: April 2023

Introduction: As the increase in electrification poses new demands on power delivery, the quality of the distribution system is paramount. Substations are a critical part of power grids that allow for control and service of the electrical distribution system. Substations are currently developed in a project-based and manually intensive manner, with a high degree of manual work and lengthy lead times. Substations are primarily sold through tenders that are accompanied by an inherent need for engineering-to-order activities. Although necessary, these activities present a paradox as tender processes must be agile and fast. To remedy this shortcoming, this article outlines a knowledge capture and reuse methodology to standardize and automate the product development processes of substation design.Methods: A novel framework for substation design is presented that implements knowledge-based engineering (KBE) and artificial intelligence methods in computer vision to capture knowledge. In addition, a product configuration system is presented, utilizing high-level CAD templates. The development has followed the KBE methodology MOKA.Results: The proposed framework has been implemented on several company cases where three (simplified) are presented in this paper. The framework decreased the time to create a 3D model from a basic electric single line diagram by performing the identification and design tasks in an automated fashion.Discussion: Ultimately, the framework will allow substation design companies to increase competitiveness through automation and knowledge management and enable more tenders to be answered without losing engineering quality.
Association of immune-mediated inflammatory diseases with depression and anxiety in patients with type 2 diabetes: A nationwide population-based study
Authors: Kwon Oh Chan , Kim Yuna , Chun Jaeyoung , Han Kyungdo , Park Min-Chan , Kim Ryul , Kim Jie-Hyun , Youn Young Hoon , Park Hyojin 
Published: April 2023

ObjectivePatients with type 2 diabetes (T2DM) are at a high risk of developing depression and anxiety. To better stratify the risk, we aimed to assess whether the presence of immune-mediated inflammatory diseases (IMIDs) confers a higher risk of depression and anxiety in these patients.MethodsPatients with T2DM without prior depression or anxiety who underwent national health examination between 2009 and 2012 (n = 1,612,705) were enrolled from the nationwide health check-up data from Korean National Health Insurance Service. The outcome events were incident depression and anxiety, defined as International Classification of Diseases, 10th Revision codes F32–F33 and F40–F41, respectively. Multivariable Cox proportional hazard regression analyses were conducted to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) according to the existence of IMIDs.ResultsOver an average follow-up time of 6.4 years, existence of gut IMIDs was associated with a higher risk of depression (aHR: 1.28 [95% CI: 1.08–1.53]) and anxiety (1.22 [1.06–1.42]). Existence of joint IMIDs was associated with a higher risk of depression (1.34 [1.31–1.37]) and anxiety (1.31 [1.29–1.34]). Existence of skin IMID was associated with a higher risk of depression (1.18 [1.14–1.23]) and anxiety (1.13 [1.09–1.16]). The effect sizes of IMIDs on depression and anxiety were larger in those with ≥ 2 IMIDs (1.42 [1.19–1.69] and 1.49 [1.29–1.72], respectively) than in those with one IMID (1.30 [1.27–1.32] and 1.26 [1.24–1.28], respectively).ConclusionIn patients with T2DM, presence of IMIDs was associated with a higher risk of depression and anxiety. More stringent attention and screening for anxiety and depression should be encouraged in patients with T2DM and comorbid IMIDs due to clinical implications of psychological distress on patient-reported outcomes and prognosis.
Changes in the Profile of Fecal Microbiota and Metabolites as Well as Serum Metabolites and Proteome After Dietary Inulin Supplementation in Dairy Cows With Subclinical Mastitis
Authors: Wang Yue , Nan Xuemei , Zhao Yiguang , Jiang Linshu , Wang Hui , Zhang Fan , Hua Dengke , Liu Jun , Yang Liang , Yao Junhu , Xiong Benhai 
Published: April 2023

Graphical AbstractEffects of dietary inulin supplementation on fecal microorganisms and metabolites, as well as serum metabolites and proteins in dairy cows with subclinical mastitis.
Amino acid variation at VP1-145 of enterovirus A71 determines the viral infectivity and receptor usage in a primary human intestinal model
Authors: Aknouch Ikrame , García-Rodríguez Inés , Giugliano Francesca Paola , Calitz Carlemi , Koen Gerrit , van Eijk Hetty , Johannessson Nina , Rebers Sjoerd , Brouwer Lieke , Muncan Vanesa , Stittelaar Koert J. , Pajkrt Dasja , Wolthers Katja C. , Sridhar Adithya 
Published: April 2023

Enterovirus A71 (EV-A71) can elicit a wide variety of human diseases such as hand, foot, and mouth disease and severe or fatal neurological complications. It is not clearly understood what determines the virulence and fitness of EV-A71. It has been observed that amino acid changes in the receptor binding protein, VP1, resulting in viral binding to heparan sulfate proteoglycans (HSPGs) may be important for the ability of EV-A71 to infect neuronal tissue. In this study, we identified that the presence of glutamine, as opposed to glutamic acid, at VP1-145 is key for viral infection in a 2D human fetal intestinal model, consistent with previous findings in an airway organoid model. Moreover, pre-treatment of EV-A71 particles with low molecular weight heparin to block HSPG-binding significantly reduced the infectivity of two clinical EV-A71 isolates and viral mutants carrying glutamine at VP1-145. Our data indicates that mutations in VP1 leading to HSPG-binding enhances viral replication in the human gut. These mutations resulting in increased production of viral particles at the primary replication site could lead to a higher risk of subsequent neuroinfection.ImportanceWith the near eradication of polio worldwide, polio-like illness (as is increasingly caused by EV-A71 infections) is of emerging concern. EV-A71 is indeed the most neurotropic enterovirus that poses a major threat globally to public health and specifically in infants and young children. Our findings will contribute to the understanding of the virulence and the pathogenicity of this virus. Further, our data also supports the identification of potential therapeutic targets against severe EV-A71 infection especially among infants and young children. Furthermore, our work highlights the key role of HSPG-binding mutations in the disease outcome of EV-A71. Additionally, EV-A71 is not able to infect the gut (the primary replication site in humans) in traditionally used animal models. Thus, our research highlights the need for human-based models to study human viral infections.