bluuebunny/crossref_metadata_2025 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

Introduction

Cardiomyopathy 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.

Methods

The 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.

Results

In 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.

Conclusions

The 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.
Block and unplugged programming can be mutually beneficial: A study of learning activities in a 6th grade class in Norway
Authors: Heim Greta , Wang Oskar Jensen
Published: April 2023

In the new Norwegian national curricula, programming and interdisciplinary work have been introduced as two central elements. Furthermore, computational thinking is part of the core elements of the mathematics curriculum. In this paper, we present the findings from a small-scale study within the subjects of mathematics and food and health. The aim was to see if these two subjects could be used as an arena for working with parts of computational thinking, in this case algorithmic thinking and collaboration, and expanding the students’ understanding of what programming can be. We think there is a gap in the research regarding this topic, and therefore we wanted to look into this. The students who took part in the study carried out two lessons, one in each subject. In mathematics, the focus was on block programming, while food and health can be seen as unplugged programming. Our findings are based on feedback from 36 students and observations from the lessons. The main finding is that most of the students could not see a link between programming and food and health. Only seven students expressed something that indicated that they did see a link. Thus, it seems like most of the students could not see similarities between the algorithmic thinking in block programming and recipes in food and health.
Explaining inequalities of homeschooling in Germany during the first COVID-19 lockdown
Authors: Sari Elif , Bittmann Felix , Homuth Christoph
Published: April 2023

Current studies suggest that the COVID-19 pandemic is worsening existing social inequalities in the field of education worldwide. In this paper, we argue that the pandemic is especially challenging for students from socially disadvantaged and educationally deprived homes, as parental engagement and resources are very important in terms of guiding and supporting students’ learning processes during this school closure period. To examine how well parents were able to help their children with schoolwork during the homeschooling period in Germany, we used data from the German National Educational Panel Study (NEPS, n = 3,714) collected during the first such period in May/June 2020 when students were in Grade 7. Taking known mechanisms of inequality of educational opportunity into account, we explored the effects of parents’ aspirations and cultural, social, and economic capital on their ability to help their children. Our results showed that although the majority of the examined parents were able to provide good schoolwork support, as expected, we found inequalities related to social background. Parents with low education were twice as likely as highly educated parents to be unable to provide sufficient support. In our multivariate analyses, family resources had a significant positive effect on the likelihood of a parent being able to help. Moreover, regardless of the social or cultural capital endowment of the parents, good household technical equipment was associated with a higher probability of support. Thus, ensuring that students have access to technical home equipment could be a way to promote an educationally supportive learning environment across all social groups.
Permian trilobites and the applicability of the “living fossil” concept to extinct clades
Authors: Hopkins Melanie J. , Wagner Peter J. , Jordan Katherine J.
Published: April 2023

Some taxa occupy our imaginations as “living fossils” because they were known from the fossil record before being discovered alive today. Other taxa are considered “living fossils” because modern relatives bear a strong morphological resemblance to fossil relatives, or because they occupy a contracted geographic range or have less diversity now than in the past, or because they represent phylogenetic diversity that requires conservation. A characterizing feature of living fossils–and thus an implicit assumption of all criteria–is that the “living fossil” of interest is extant. However, the general research questions that “living fossils” inspire–Why do rates of evolution vary across organisms, across traits, and across time? Why do some clades decline in diversity over extended periods?–may be applied to any clade, including completely extinct clades. We propose that there is nothing special about “now” when it comes to pursuing these questions and that it is unnecessarily limiting to restrict research programs to clades for which an extant member meets some conception of the “living fossil” moniker. To this end, we investigate the extent to which Permian trilobites might resemble “living fossils,” albeit from the perspective of 253 million years ago, when the last trilobites were still alive. We do so by comparing the taxonomic diversity, geographic range, and morphological disparity of trilobites living in the Permian to earlier time periods. We find that Permian trilobites meet most definitions of living fossils, although our assessment of morphological change and character retention depend on taxonomic scale.
Legal actions in Brazilian air transport: A machine learning and multinomial logistic regression analysis
Authors: Torres Gabriel de Oliveira , Guterres Marcelo Xavier , Celestino Victor Rafael Rezende
Published: April 2023

In Brazil, one of the most harmful costs for airlines is the number of lawsuits filed against them. It is a problem that can affect its operations, reduce the entry of new competitors and create legal uncertainty in the country. This work seeks to highlight the factors which most contribute to the rise of judicial indemnities, discuss the most relevant issues and identify the best techniques to predict the indemnified values. The objective is to provide subsidies for airlines to mitigate the number of legal actions by using machine learning models. This research contributes by discussing one of the most relevant subjects in Brazilian air transport and comparing the machine learning models’ performance. The study is based on lawsuits between 2016 and 2021 using the companies’ data. The performance of Naive Bayes, Random Forest, Support Vector Machines, and Multinomial Logistic Regression models are evaluated through the accuracy, area under the ROC curve, and confusion matrix. The results showed better predictive power for Random Forest and Logistic Regression. The latter showed that flight delays, cancellations, and airline faults have a negative effect on indemnities. The above-average compensation is a tendency in some states, being the moral damage awarded to customers the main cause of higher compensation.
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.
Integration of HIV care into maternal and child health services in the global IeDEA consortium
Authors: Humphrey John , Nagel Elizabeth , Carlucci James G. , Edmonds Andrew , Kinikar Aarti , Anderson Kim , Leroy Valériane , Machado Daisy , Yin Dwight E. , Tulio Luque Marco , Amorissani-Folquet Madeleine , Mbewe Safari , Suwanlerk Tulathip , Munyaneza Athanase , Patel Rena C. , Musick Beverly , Abuogi Lisa , Wools-Kaloustian Kara
Published: April 2023

The WHO recommends the integration of routine HIV services within maternal and child health (MCH) services to reduce the fragmentation of and to promote retention in care for pregnant and postpartum women living with HIV (WWH) and their infants and children exposed to HIV (ICEH). During 2020–2021, we surveyed 202 HIV treatment sites across 40 low- and middle-income countries within the global International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. We determined the proportion of sites providing HIV services integrated within MCH clinics, defined as full [HIV care and antiretroviral treatment (ART) initiation in MCH clinic], partial (HIV care or ART initiation in MCH clinic), or no integration. Among sites serving pregnant WWH, 54% were fully and 21% partially integrated, with the highest proportions of fully integrated sites in Southern Africa (80%) and East Africa (76%) compared to 14%–40% in other regions (i.e., Asia-Pacific; the Caribbean, Central and South America Network for HIV Epidemiology; Central Africa; West Africa). Among sites serving postpartum WWH, 51% were fully and 10% partially integrated, with a similar regional integration pattern to sites serving pregnant WWH. Among sites serving ICEH, 56% were fully and 9% were partially integrated, with the highest proportions of fully integrated sites in East Africa (76%), West Africa (58%) and Southern Africa (54%) compared to ≤33% in the other regions. Integration was heterogenous across IeDEA regions and most prevalent in East and Southern Africa. More research is needed to understand this heterogeneity and the impacts of integration on MCH outcomes globally.
Bioactive lipids as biomarkers of adverse reactions associated with apheresis platelet concentrate transfusion
Authors: Duchez Anne-Claire , Fauteux-Daniel Sébastien , Sut Caroline , Ebermeyer Theo , Heestermans Marco , Arthaud Charles-Antoine , Eyraud Marie-Ange , Prier Amélie , Audoux Estelle , Bertrand-Michel Justine , Payrastre Bernard , Garraud Olivier , Boilard Eric , Hamzeh-Cognasse Hind , Cognasse Fabrice
Published: April 2023

Platelet concentrate (PC) transfusion seeks to provide haemostasis in patients presenting severe central thrombocytopenia or severe bleeding. PCs may induce adverse reactions (AR) that can occasionally be severe (SAR). PCs contain active biomolecules such as cytokines and lipid mediators. The processing and storage of PCs creates so-called structural and biochemical storage lesions that accumulate when blood products reach their shelf life. We sought to investigate lipid mediators as bioactive molecules of interest during storage and review associations with adverse reactions post-transfusion. To facilitate understanding, we focused on single donor apheresis (SDA) PCs with approximately 31.8% of PCs being delivered in our setting. Indeed, pooled PCs are the most widely transfused products, but the study of a single donor lipid mediator is easier to interpret. We are investigating key lipid mediators involved in AR. Adverse reactions were closely monitored in accordance with current national and regional haemovigilance protocols. Residual PCs were analysed post-transfusion in a series of observations, both with and without severe reactions in recipients. A decrease in the lysophosphatidylcholine species to produce the lysophosphatidic acid species has been observed during storage and in the case of AR. Lysophosphatidic acid increased with primarily platelet-inhibitor lipids. Anti-inflammatory platelet-induced inhibition lipids were weakly expressed in cases of severe adverse reactions. We therefore propose that a decrease in lysophosphatidylcholine and an increase in lysophosphatidic acid can prospectively predict serious adverse transfusion reactions.
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

Background

Phosphorylation 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.

Results

Herein, 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.

Conclusion

We 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

Background

Acute 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.

Methods

In 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.

Results

Given 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.

Conclusion

Our 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.
Immunotherapy: A promising novel endometriosis therapy
Authors: Li Wenshu , Lin Aimin , Qi Lin , Lv Xin , Yan Shenghuan , Xue Jing , Mu Nan
Published: April 2023

Endometriosis is a common disease of the female reproductive system and has malignant features. Although endometriosis by itself is a benign disease, its erosive growth characteristics lead to severe pelvic pain and female infertility. Unfortunately, several aspects of the pathogenesis of endometriosis are still unclear. Furthermore, the clinical therapeutic methods are unsatisfactory. The recurrence rate of endometriosis is high. Accumulating evidence suggests that the onset and development of endometriosis are closely related to the abnormal function of the female autoimmune system, especially the function of some immune cells such as the aggregation of neutrophils, abnormal differentiation of macrophages, decreased cytotoxicity of NK cells, and abnormal function of T- and B-cell lines. Therefore, immunotherapy is probably a novel therapeutic strategy for endometriosis besides surgery and hormone therapy. However, information regarding the clinical application of immunotherapy in the treatment of endometriosis is very limited. This article aimed to review the effects of existing immunomodulators on the development of endometriosis, including immune cell regulators and immune factor regulators. These immunomodulators clinically or experimentally inhibit the pathogenesis and development of endometriosis lesions by acting on the immune cells, immune factors, or immune-related signaling pathways. Thus, immunotherapy is probably a novel and effective clinical treatment choice for endometriosis. Experimental studies of the detailed mechanism of immunotherapy and large-scale clinical studies about the effectiveness and safety of this promising therapeutic method are required in the future.
Identification and validation of a novel CD8+ T cell-associated prognostic model based on ferroptosis in acute myeloid leukemia
Authors: Jiang Ge , Jin Peng , Xiao Xiao , Shen Jie , Li Ran , Zhang Yunxiang , Li Xiaoyang , Xue Kai , Li Junmin
Published: April 2023

Acute myeloid leukemia (AML) is a highly aggressive cancer with great heterogeneity and variability in prognosis. Though European Leukemia Net (ELN) 2017 risk classification has been widely used, nearly half of patients were stratified to “intermediate” risk and requires more accurate classification via excavating biological features. As new evidence showed that CD8+ T cell can kill cancer cells through ferroptosis pathway. We firstly use CIBERSORT algorithm to divide AMLs into CD8+ high and CD8+ low T cell groups, then 2789 differentially expressed genes (DEGs) between groups were identified, of which 46 ferroptosis-related genes associated with CD8+ T cell were sorted out. GO, KEGG analysis and PPI network were conducted based on these 46 DEGs. By jointly using LASSO algorithm and Cox univariate regression, we generated a 6-gene prognostic signature comprising VEGFA, KLHL24, ATG3, EIF2AK4, IDH1 and HSPB1. Low-risk group shows a longer overall survival. We then validated the prognostic value of this 6-gene signature using two independent external datasets and patient sample collection dataset. We also proved that incorporation of the 6-gene signature obviously enhanced the accuracy of ELN risk classification. Finally, gene mutation analysis, drug sensitive prediction, GSEA and GSVA analysis were conducted between high-risk and low-risk AML patients. Collectively, our findings suggested that the prognostic signature based on CD8+ T cell-related ferroptosis genes can optimize the risk stratification and prognostic prediction of AML patients.
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

Background

FLAIR-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.

Methods

We 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.

Results

A 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.

Conclusion

FLAMES 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 objectives

Stroke 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.

Methods

This 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.

Results

A 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 < 0.001), HC and IS (F = 5.07, P < 0.001), and HRIS and IS (F = 2.79, P < 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 < 0.01).

Discussion

In 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.
Future digital twins: emulating a highly complex marine biogeochemical model with machine learning to predict hypoxia
Authors: Skákala Jozef , Awty-Carroll Katie , Menon Prathyush P. , Wang Ke , Lessin Gennadi
Published: April 2023

The Machine learning (ML) revolution is becoming established in oceanographic research, but its applications to emulate marine biogeochemical models are still rare. We pioneer a novel application of machine learning to emulate a highly complex physical-biogeochemical model to predict marine oxygen in the shelf-sea environment. The emulators are developed with intention of supporting future digital twins for two key stakeholder applications: (i) prediction of hypoxia for aquaculture and fisheries, (ii) extrapolation of oxygen from marine observations. We identify the key drivers behind oxygen concentrations and determine the constrains on observational data for a skilled prediction of marine oxygen across the whole water column. Through this we demonstrate that ML models can be very useful in informing observation measurement arrays. We compare the performance of multiple different ML models, discuss the benefits of the used approaches and identify outstanding issues, such as limitations imposed by the spatio-temporal resolution of the training/validation data.
Manta and devil ray aggregations: conservation challenges and developments in the field
Authors: Palacios Marta D. , Stewart Joshua D. , Croll Donald A. , Cronin Melissa R. , Trejo-Ramírez Abel , Stevens Guy M. W. , Lezama-Ochoa Nerea , Zilliacus Kelly M. , González−Armas Rogelio , Notarbartolo di Sciara Giuseppe , Galván−Magaña Felipe
Published: April 2023

Manta and devil rays (mobulids) are filter feeding elasmobranchs with extreme K-selective life histories found circumglobally from temperate to tropical waters. Their vulnerability to fisheries exploitation, bycatch, boat collisions, entanglement and unregulated tourism is exacerbated by their aggregative behavior. Studies have identified aggregation sites around the world for all nine mobulid species, with these groupings varying from a few individuals to thousands. However, the terminology used to define these aggregations and the drivers underpinning them remain unclear, hindering the development of effective management and conservation strategies. Here, we analyze aggregation behavior for mobulid species, providing consistent definitions for grouping events and summarizing the existing research on drivers and environmental factors triggering these events. We find that aggregation behaviors facilitate socializing and key life history functions in mobulids, including feeding, courtship and mating, predation avoidance, cleaning, and thermoregulation. Conservation threats and management mitigation opportunities associated with aggregations sites include fisheries, tourism, spatial protection, and climate change. Finally, we highlight knowledge gaps for future research prioritization and developments in the field for the identification of aggregation sites, the study of aggregation size and demographics and the functions and timing of aggregations.
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

Objective

Patients 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.

Methods

Patients 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.

Results

Over 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).

Conclusion

In 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.
Application of nanoparticles in the diagnosis and treatment of chronic kidney disease
Authors: Yang Kaibi , Shang Yiwei , Yang Nan , Pan Shujun , Jin Juan , He Qiang
Published: April 2023

With the development of nanotechnology, nanoparticles have been used in various industries. In medicine, nanoparticles have been used in the diagnosis and treatment of diseases. The kidney is an important organ for waste excretion and maintaining the balance of the internal environment; it filters various metabolic wastes. Kidney dysfunction may result in the accumulation of excess water and various toxins in the body without being discharged, leading to complications and life-threatening conditions. Based on their physical and chemical properties, nanoparticles can enter cells and cross biological barriers to reach the kidneys and therefore, can be used in the diagnosis and treatment of chronic kidney disease (CKD). In the first search, we used the English terms “Renal Insufficiency, Chronic” [Mesh] as the subject word and terms such as “Chronic Renal Insufficiencies,” “Chronic Renal Insufficiency,” “Chronic Kidney Diseases,” “Kidney Disease, Chronic,” “Renal Disease, Chronic” as free words. In the second search, we used “Nanoparticles” [Mesh] as the subject word and “Nanocrystalline Materials,” “Materials, Nanocrystalline,” “Nanocrystals,” and others as free words. The relevant literature was searched and read. Moreover, we analyzed and summarized the application and mechanism of nanoparticles in the diagnosis of CKD, application of nanoparticles in the diagnosis and treatment of renal fibrosis and vascular calcification (VC), and their clinical application in patients undergoing dialysis. Specifically, we found that nanoparticles can detect CKD in the early stages in a variety of ways, such as via breath sensors that detect gases and biosensors that detect urine and can be used as a contrast agent to avoid kidney damage. In addition, nanoparticles can be used to treat and reverse renal fibrosis, as well as detect and treat VC in patients with early CKD. Simultaneously, nanoparticles can improve safety and convenience for patients undergoing dialysis. Finally, we summarize the current advantages and limitations of nanoparticles applied to CKD as well as their future prospects.
Cardiovascular diseases prediction by machine learning incorporation with deep learning
Authors: Subramani Sivakannan , Varshney Neeraj , Anand M. Vijay , Soudagar Manzoore Elahi M. , Al-keridis Lamya Ahmed , Upadhyay Tarun Kumar , Alshammari Nawaf , Saeed Mohd , Subramanian Kumaran , Anbarasu Krishnan , Rohini Karunakaran
Published: April 2023

It is yet unknown what causes cardiovascular disease (CVD), but we do know that it is associated with a high risk of death, as well as severe morbidity and disability. There is an urgent need for AI-based technologies that are able to promptly and reliably predict the future outcomes of individuals who have cardiovascular disease. The Internet of Things (IoT) is serving as a driving force behind the development of CVD prediction. In order to analyse and make predictions based on the data that IoT devices receive, machine learning (ML) is used. Traditional machine learning algorithms are unable to take differences in the data into account and have a low level of accuracy in their model predictions. This research presents a collection of machine learning models that can be used to address this problem. These models take into account the data observation mechanisms and training procedures of a number of different algorithms. In order to verify the efficacy of our strategy, we combined the Heart Dataset with other classification models. The proposed method provides nearly 96 percent of accuracy result than other existing methods and the complete analysis over several metrics has been analysed and provided. Research in the field of deep learning will benefit from additional data from a large number of medical institutions, which may be used for the development of artificial neural network structures.
Mapping the use of computational modelling and simulation in clinics: A survey
Authors: Lesage Raphaëlle , Van Oudheusden Michiel , Schievano Silvia , Van Hoyweghen Ine , Geris Liesbet , Capelli Claudio
Published: April 2023

In silico medicine describes the application of computational modelling and simulation (CM&S) to the study, diagnosis, treatment or prevention of a disease. Tremendous research advances have been achieved to facilitate the use of CM&S in clinical applications. Nevertheless, the uptake of CM&S in clinical practice is not always timely and accurately reflected in the literature. A clear view on the current awareness, actual usage and opinions from the clinicians is needed to identify barriers and opportunities for the future of in silico medicine. The aim of this study was capturing the state of CM&S in clinics by means of a survey toward the clinical community. Responses were collected online using the Virtual Physiological Human institute communication channels, engagement with clinical societies, hospitals and individual contacts, between 2020 and 2021. Statistical analyses were done with R. Participants (n = 163) responded from all over the world. Clinicians were mostly aged between 35 and 64 years-old, with heterogeneous levels of experience and areas of expertise (i.e., 48% cardiology, 13% musculoskeletal, 8% general surgery, 5% paediatrics). The CM&S terms “Personalised medicine” and “Patient-specific modelling” were the most well-known within the respondents. “In silico clinical trials” and “Digital Twin” were the least known. The familiarity with different methods depended on the medical specialty. CM&S was used in clinics mostly to plan interventions. To date, the usage frequency is still scarce. A well-recognized benefit associated to CM&S is the increased trust in planning procedures. Overall, the recorded level of trust for CM&S is high and not proportional to awareness level. The main barriers appear to be access to computing resources, perception that CM&S is slow. Importantly, clinicians see a role for CM&S expertise in their team in the future. This survey offers a snapshot of the current situation of CM&S in clinics. Although the sample size and representativity could be increased, the results provide the community with actionable data to build a responsible strategy for accelerating a positive uptake of in silico medicine. New iterations and follow-up activities will track the evolution of responses over time and contribute to strengthen the engagement with the medical community.
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 Abstract

Effects 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.

Importance

With 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.