bluuebunny/crossref_metadata_2025_split huggingface dataset:
High levels of endothelial ICAM-1 prohibit natalizumab mediated abrogation of CD4+ T cell arrest on the inflamed BBB under flow in vitro
Authors: Soldati Sasha , Bär Alexander , Vladymyrov Mykhailo , Glavin Dale , McGrath James L. , Gosselet Fabien , Nishihara Hideaki , Goelz Susan , Engelhardt Britta 
Published: May 2023

Abstract
Introduction
The humanized anti-α4 integrin blocking antibody natalizumab (NTZ) is an effective treatment for relapsing–remitting multiple sclerosis (RRMS) that is associated with the risk of progressive multifocal leukoencephalopathy (PML). While extended interval dosing (EID) of NTZ reduces the risk for PML, the minimal dose of NTZ required to maintain its therapeutic efficacy remains unknown.

Objective
Here we aimed to identify the minimal NTZ concentration required to inhibit the arrest of human effector/memory CD4+ T cell subsets or of PBMCs to the blood–brain barrier (BBB) under physiological flow in vitro.

Results
Making use of three different human in vitro BBB models and in vitro live-cell imaging we observed that NTZ mediated inhibition of α4-integrins failed to abrogate T cell arrest to the inflamed BBB under physiological flow. Complete inhibition of shear resistant T cell arrest required additional inhibition of β2-integrins, which correlated with a strong upregulation of endothelial intercellular adhesion molecule (ICAM)-1 on the respective BBB models investigated. Indeed, NTZ mediated inhibition of shear resistant T cell arrest to combinations of immobilized recombinant vascular cell adhesion molecule (VCAM)-1 and ICAM-1 was abrogated in the presence of tenfold higher molar concentrations of ICAM-1 over VCAM-1. Also, monovalent NTZ was less potent than bivalent NTZ in inhibiting T cell arrest to VCAM-1 under physiological flow. In accordance with our previous observations ICAM-1 but not VCAM-1 mediated T cell crawling against the direction of flow.

Conclusion
Taken together, our in vitro observations show that high levels of endothelial ICAM-1 abrogate NTZ mediated inhibition of T cell interaction with the BBB. EID of NTZ in MS patients may thus require consideration of the inflammatory status of the BBB as high levels of ICAM-1 may provide an alternative molecular cue allowing for pathogenic T cell entry into the CNS in the presence of NTZ.
Functional and evolutionary study of MLO gene family in the regulation of Sclerotinia stem rot resistance in Brassica napus L.
Authors: Liu Jie , Wu Yupo , Zhang Xiong , Gill Rafaqat Ali , Hu Ming , Bai Zetao , Zhao Chuanji , Zhang Yi , Liu Yueying , Hu Qiong , Cheng Xiaohui , Huang Junyan , Liu Lijiang , Yan Shunping , Liu Shengyi 
Published: May 2023

Abstract
Background
Oilseed rape (Brassica napus L.) is known as one of the most important oilseed crops cultivated around the world. However, its production continuously faces a huge challenge of Sclerotinia stem rot (SSR), a destructive disease caused by the fungus Sclerotinia sclerotiorum, resulting in huge yield loss annually. The SSR resistance in B. napus is quantitative and controlled by a set of minor genes. Identification of these genes and pyramiding them into a variety are a major strategy for SSR resistance breeding in B. napus.

Results
Here, we performed a genome-wide association study (GWAS) using a natural population of B. napus consisting of 222 accessions to identify BnaA08g25340D (BnMLO2_2) as a candidate gene that regulates the SSR resistance. BnMLO2_2 was a member of seven homolog genes of Arabidopsis Mildew Locus O 2 (MLO2) and the significantly SNPs were mainly distributed in the promoter of BnMLO2_2, suggesting a role of BnMLO2_2 expression level in the regulation of SSR resistance. We expressed BnMLO2_2 in Arabidopsis and the transgenic plants displayed an enhanced SSR resistance. Transcriptome profiling of different tissues of B. napus revealed that BnMLO2_2 had the most expression level in leaf and silique tissues among all the 7 BnMLO2 members and also expressed higher in the SSR resistant accession than in the susceptible accession. In Arabidopsis, mlo2 plants displayed reduced resistance to SSR, whereas overexpression of MLO2 conferred plants an enhanced SSR resistance. Moreover, a higher expression level of MLO2 showed a stronger SSR resistance in the transgenic plants. The regulation of MLO2 in SSR resistance may be associated with the cell death. Collinearity and phylogenetic analysis revealed a large expansion of MLO family in Brassica crops.

Conclusion
Our study revealed an important role of BnMLO2 in the regulation of SSR resistance and provided a new gene candidate for future improvement of SSR resistance in B. napus and also new insights into understanding of MLO family evolution in Brassica crops.
An association of CSF apolipoprotein E glycosylation and amyloid-beta 42 in individuals who carry the APOE4 allele
Authors: Meuret Cristiana J. , Hu Yueming , Smadi Sabrina , Bantugan Mikaila Ann , Xian Haotian , Martinez Ashley E. , Krauss Ronald M. , Ma Qiu-Lan , Nedelkov Dobrin , Yassine Hussein N. 
Published: May 2023

AbstractCarrying the apolipoprotein E (ApoE) Ɛ4 allele is associated with an increased risk of cerebral amyloidosis and late-onset Alzheimer’s disease, but the degree to which apoE glycosylation affects its development is not clear. In a previous pilot study, we identified distinct total and secondary isoform-specific cerebral spinal fluid (CSF) apoE glycosylation profiles, with the E4 isoform having the lowest glycosylation percentage (E2 > E3 > E4). In this work, we extend the analysis to a larger cohort of individuals (n = 106), utilizing matched plasma and CSF samples with clinical measures of AD biomarkers. The results confirm the isoform-specific glycosylation of apoE in CSF, resulting from secondary CSF apoE glycosylation patterns. CSF apoE glycosylation percentages positively correlated with CSF Aβ42 levels (r = 0.53, p < 0.0001). These correlations were not observed for plasma apoE glycosylation. CSF total and secondary apoE glycosylation percentages also correlated with the concentration of CSF small high-density lipoprotein particles (s-HDL-P), which we have previously shown to be correlated with CSF Aβ42 levels and measures of cognitive function. Desialylation of apoE purified from CSF showed reduced Aβ42 degradation in microglia with E4 > E3 and increased binding affinity to heparin. These results indicate that apoE glycosylation has a new and important role in influencing brain Aβ metabolism and can be a potential target of treatment.
Identifying the neurodevelopmental and psychiatric signatures of genomic disorders associated with intellectual disability: a machine learning approach
Authors: Donnelly Nicholas , Cunningham Adam , Salas Sergio Marco , Bracher-Smith Matthew , Chawner Samuel , Stochl Jan , Ford Tamsin , Raymond F. Lucy , Escott-Price Valentina , van den Bree Marianne B. M. 
Published: May 2023

Abstract
Background
Genomic conditions can be associated with developmental delay, intellectual disability, autism spectrum disorder, and physical and mental health symptoms. They are individually rare and highly variable in presentation, which limits the use of standard clinical guidelines for diagnosis and treatment. A simple screening tool to identify young people with genomic conditions associated with neurodevelopmental disorders (ND-GCs) who could benefit from further support would be of considerable value. We used machine learning approaches to address this question.

Method
A total of 493 individuals were included: 389 with a ND-GC, mean age = 9.01, 66% male) and 104 siblings without known genomic conditions (controls, mean age = 10.23, 53% male). Primary carers completed assessments of behavioural, neurodevelopmental and psychiatric symptoms and physical health and development. Machine learning techniques (penalised logistic regression, random forests, support vector machines and artificial neural networks) were used to develop classifiers of ND-GC status and identified limited sets of variables that gave the best classification performance. Exploratory graph analysis was used to understand associations within the final variable set.

Results
All machine learning methods identified variable sets giving high classification accuracy (AUROC between 0.883 and 0.915). We identified a subset of 30 variables best discriminating between individuals with ND-GCs and controls which formed 5 dimensions: conduct, separation anxiety, situational anxiety, communication and motor development.

Limitations
This study used cross-sectional data from a cohort study which was imbalanced with respect to ND-GC status. Our model requires validation in independent datasets and with longitudinal follow-up data for validation before clinical application.

Conclusions
In this study, we developed models that identified a compact set of psychiatric and physical health measures that differentiate individuals with a ND-GC from controls and highlight higher-order structure within these measures. This work is a step towards developing a screening instrument to identify young people with ND-GCs who might benefit from further specialist assessment.
Caroli syndrome associated with atrial septal defect and polydactyly: a case report
Authors: Ghassa Ali , Khouri Lina 
Published: May 2023

Abstract
Introduction
Caroli disease is multifocal segmental dilatation of the large intrahepatic bile ducts that connect to the main duct. It is considered a rare disease with an incidence rate of 1 in 1,000,000 births. There are two types of Caroli: the first type is the simple type, Caroli disease, which includes only cystic dilatation of the intrahepatic bile ducts. The second is called Caroli syndrome, which consists of Caroli disease and congenital hepatic fibrosis and might lead to portal hypertension leading to esophageal varices and splenomegaly. Atrial septal defect is one of the most common congenital heart diseases, occurring when the connection between the left and the right atriums fails to close. Polydactyly is one of the most common congenital malformations of the hands and feet. It manifests in excess fingers on the hands or toes.

Case presentation
A 6-year-old Arab girl presented to the hospital with abdominal pain for the last month with abdominal enlargement. The patient was already diagnosed with Caroli disease and polydactyly (six fingers on each limb) when she was born. Investigations including complete blood count, blood smear, bone marrow biopsy, esophagoscopy, abdominal ultrasound, and computed tomography scan showed splenomegaly associated with hypersplenism, fourth-grade non-bleeding varices, intrahepatic cystic formations in the left and right lobes, and an atrial septal defect with a left-to-right shunt. The patient was scheduled for a splenectomy after she was vaccinated with the appropriate vaccines. After follow-up for a week in the hospital, complete blood count showed an improvement. A month after that, the patient had liver abscesses and biliary fistula that were treated appropriately and her symptoms resolved.

Conclusion
The association of liver diseases, polydactyly, and congenital heart diseases is extremely rare and was only documented few times in the literature. However, to our knowledge, atrial septal defect has never been part of this combination before. The family history also makes this case unique and strongly suggests genetic etiology.
Menopause causes metabolic and cognitive impairments in a chronic cerebral hypoperfusion model of vascular contributions to cognitive impairment and dementia
Authors: Gannon Olivia J. , Naik Janvie S. , Riccio David , Mansour Febronia M. , Abi-Ghanem Charly , Salinero Abigail E. , Kelly Richard D. , Brooks Heddwen L. , Zuloaga Kristen L. 
Published: May 2023

Abstract
Background
The vast majority of women with dementia are post-menopausal. Despite clinical relevance, menopause is underrepresented in rodent models of dementia. Before menopause, women are less likely than men to experience strokes, obesity, and diabetes—known risk factors for vascular contributions to cognitive impairment and dementia (VCID). During menopause, ovarian estrogen production stops and the risk of developing these dementia risk factors spikes. Here, we aimed to determine if menopause worsens cognitive impairment in VCID. We hypothesized that menopause would cause metabolic dysfunction and increase cognitive impairment in a mouse model of VCID.

Methods
We performed a unilateral common carotid artery occlusion surgery to produce chronic cerebral hypoperfusion and model VCID in mice. We used 4-vinylcyclohexene diepoxide to induce accelerated ovarian failure and model menopause. We evaluated cognitive impairment using behavioral tests including novel object recognition, Barnes maze, and nest building. To assess metabolic changes, we measured weight, adiposity, and glucose tolerance. We explored multiple aspects of brain pathology including cerebral hypoperfusion and white matter changes (commonly observed in VCID) as well as changes to estrogen receptor expression (which may mediate altered sensitivity to VCID pathology post-menopause).

Results
Menopause increased weight gain, glucose intolerance, and visceral adiposity. VCID caused deficits in spatial memory regardless of menopausal status. Post-menopausal VCID specifically led to additional deficits in episodic-like memory and activities of daily living. Menopause did not alter resting cerebral blood flow on the cortical surface (assessed by laser speckle contrast imaging). In the white matter, menopause decreased myelin basic protein gene expression in the corpus callosum but did not lead to overt white matter damage (assessed by Luxol fast blue). Menopause did not significantly alter estrogen receptor expression (ERα, ERβ, or GPER1) in the cortex or hippocampus.

Conclusions
Overall, we have found that the accelerated ovarian failure model of menopause caused metabolic impairment and cognitive deficits in a mouse model of VCID. Further studies are needed to identify the underlying mechanism. Importantly, the post-menopausal brain still expressed estrogen receptors at normal (pre-menopausal) levels. This is encouraging for any future studies attempting to reverse the effects of estrogen loss by activating brain estrogen receptors.
Sertraline treatment influences [18F]FE-PE2I PET imaging for Parkinsonism
Authors: Justesen Thomas E. H. , Borghammer Per , Aanerud Joel , Hovind Peter , Marner Lisbeth 
Published: May 2023

Abstract
Background
The dopamine transporter (DaT) PET ligand [18F]FE-PE2I is used to aid the diagnosis of Parkinson’s disease. After encountering four patients with a history of daily sertraline use, who all showed atypical findings on [18F]FE-PE2I PET, we suspected that the selective serotonin reuptake inhibitor (SSRI), sertraline, might interfere with the results and lead to globally reduced striatal [18F]FE-PE2I binding due to sertraline’s high affinity for DaT.

Methods
We rescanned the four patients with [18F]FE-PE2I PET after a 5-day sertraline pause. Sertraline plasma concentration was estimated based on body weight and dose, and specific binding ratios (SBR) in caudate nucleus, known to be more preserved in Parkinson’s, were used to estimate the effect on tracer binding. Comparison was made to a patient with [18F]FE-PE2I PET before and after a 7-day Modafinil pause.

Results
We found a significant effect of sertraline on caudate nucleus SBR (p = 0.029). The effect showed a linear dose-dependent relationship that corresponds to a reduction in SBR by 0.32 or 0.44 for a 75 kg male or a 65 kg female, respectively, taking a daily dose of 50 mg sertraline.

Conclusion
Sertraline is one of the most commonly used antidepressants and in contrast to other SSRI’s, sertraline show high affinity for DaT. We recommend that sertraline treatment is taken into account when patients are undergoing [18F]FE-PE2I PET especially in patients showing apparent globally reduced PE2I binding. If tolerable, pausing of the sertraline treatment should be considered, especially for doses above 50 mg/day.
Macroeconomic impacts of energy communities and individual prosumers: an assessment of transformation pathways
Authors: Vögele Stefan , Broska Lisa Hanna , Ross Andrew , Rübbelke Dirk 
Published: May 2023

Abstract
Background
Active citizen participation, especially as collective prosumers in energy communities or as individual prosumers, is vital for a sustainable energy transition. As such, it is explicitly supported by European Union policy. It is the aim of policy-makers that a large proportion of the residential energy demand will be met in this way. At present, there is limited analysis on the macroeconomic impacts of such an increase in prosumers. In this study, we develop and apply an approach for assessing the macroeconomic impacts of transformation pathways, which depict potential developments of individual and collective prosumers.

Results
The paper methodologically demonstrates how to macroeconomically assess scenarios and transformation pathways originating from cross-impact balance analyses by means of an input–output analysis. In particular, it is shown how qualitative data on future developments can be transformed into financial flows so as to enable an input–output analysis. Based on the assessment of two transformation pathways, our main findings suggest that there might be positive regional and national effects on net value added and employment as well as reductions in CO2 emissions. We find that the scale of the effects strongly depends on the spatial distribution of heterogeneous households and the underlying economic structure.

Conclusions
Our study represents a methodological advancement by showing how scenarios and transformation pathways can be assessed in terms of their macroeconomic consequences. This study shows that energy communities and individual prosumers might generate positive effects on value added and on employment. Given that households fix their energy supply options for decades, political decisions to support the energy transition in the residential sector should be taken as soon as possible.
Bibliometric analysis and visualisation of heritage buildings preservation
Authors: Mohamed Basma , Marzouk Mohamed 
Published: May 2023

Abstract
Heritage buildings are considered a source of pride for countries, and their preservation is an important pursuit. Different techniques have been adopted in this regard, and many review papers have addressed them either qualitatively or quantitatively through bibliometric analysis. Nevertheless, none of these review studies conducted a general dynamic quantitative analysis of the vast amount of scientific literature about heritage buildings preservation (HBP) research domain over time. Therefore, the current study performs a bibliometric analysis of the relevant literature considering a time of two decades (2002–2022). A total of 863 peer-reviewed journal articles were extracted from the Web of Science Core Collection database. A five-step methodology was followed employing VOSviewer, CiteSpace, and Biblioshiny as the bibliometric software tools. The main findings revealed the annual publication trends and the most prominent articles. It was also found that 60% of the literature publications were published in journals, and only 2.4% corresponded to review studies. The scientific collaboration networks showed the most prolific researchers and countries. Further, the citation analysis of journals identified the most reliable information sources for academic researchers. Finally, the conceptual and intellectual knowledge structures were visualised and studied via science mapping analysis to map the research domain evolution and determine its trending patterns and promising areas for future exploration. The conducted review provides fellow researchers with a systematic summarised database to be familiarized with the HBP literature and identify potential research opportunities to conduct state-of-the-art research with the top contributors in the field (researchers, journals, and countries). In addition, policymakers can utilize the results from this research to find expert authors and academic support to facilitate forming partnerships to plan and fund relevant research and address the practical implications of preserving valuable heritage buildings.
Effects of dietary supplementation with a carvacrol–cinnamaldehyde–thymol blend on growth performance and intestinal health of nursery pigs
Authors: Zhao Bi-Chen , Wang Tian-Hao , Chen Jian , Qiu Bai-Hao , Xu Ya-Ru , Zhang Qing , Li Jian-Jie , Wang Chun-Jiang , Nie Qiu-Feng , Li Jin-Long 
Published: May 2023

Abstract
Background
Stress, herd transfer, and food changes experienced by nursery and fattening pigs can lead to reduced performance, reduced digestion and absorption, and impaired intestinal health. Given the role of essential oils in relieving stress and improving animal welfare, we hypothesized that essential oils may improve pig performance via promoting gut health and gut homeostasis laid by EOs supplementation during nursery continuously impacts performance in fattening pigs.

Results
A total of 100 piglets (Landrace × Large White; weighted 8.08 ± 0.34 kg, weaned at d 28) were randomly selected and divided into 2 treatments: (1) basal diet (Con); (2) basal diet supplement with 0.1% complex essential oils (CEO). The experiment period was 42 days. Then weaned piglets’ growth performance and indications of intestinal health were assessed. Compared to the Con group, dietary supplemented CEO enhanced BW at 14 d (P < 0.05), and increased ADG during 1 ~ 14 d and 1 ~ 42 d (P < 0.05). Furthermore, CEO group had lower FCR during 1 ~ 42 d (P < 0.05). The CEO group also showed higher VH and VH:CD in duodenum and ileum (P < 0.05). Additionally, dietary CEO supplementation improved gut barrier function, as manifested by increased the mRNA expression of tight-junction protein and decreased serum DAO, ET and D-LA levels (P < 0.05). Finally, CEO supplementation alleviated gut inflammation, increased the activity of digestive enzymes. Importantly, piglets supplemented with CEOs during nursery also had better performance during fattening, suggesting that the establishment of intestinal health will also continuously affect subsequent digestion and absorption capacity. In short, dietary supplemented CEO improved performance and gut health via modulating increased intestine absorptive area, barrier integrity, digestive enzyme activity, and attenuating intestine inflammation. Meanwhile, essential oil supplementation during the nursery period also had a favorable effect on the performance of growing pigs.

Conclusions
Therefore, the strategy of adding CEO to pig diets as a growth promoter and enhancing intestinal health is feasible.