bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic implications of MOG-IgG detection in sera and cerebrospinal fluids
Authors: Matsumoto Yuki , Kaneko Kimihiko , Takahashi Toshiyuki , Takai Yoshiki , Namatame Chihiro , Kuroda Hiroshi , Misu Tatsuro , Fujihara Kazuo , Aoki Masashi 
Published: April 2023

AbstractThe spectrum of MOG-IgG-associated disease (MOGAD) includes optic neuritis (ON), myelitis (MY), acute disseminated encephalomyelitis (ADEM), brainstem encephalitis, cerebral cortical encephalitis (CE) and AQP4-IgG-negative neuromyelitis optica spectrum disorder (NMOSD). In MOGAD, MOG-IgG are usually detected in sera (MOG-IgGSERUM), but there have been some seronegative MOGAD cases with MOG-IgG in CSF (MOG-IgGCSF), and its diagnostic implications remains unclear.In this cross-sectional study, we identified patients with paired serum and CSF sent from all over Japan for testing MOG-IgG. Two investigators blinded to MOG-IgG status classified them into suspected MOGAD (ADEM, CE, NMOSD, ON, MY and Others) or not based on the current recommendations. The MOG-IgGSERUM and MOG-IgGCSF titres were assessed with serial 2-fold dilutions to determine end point titres [≥1:128 in serum and ≥1:1 (no dilution) in CSF were considered positive]. We analysed the relationship between MOG-IgGSERUM, MOG-IgGCSF and the phenotypes with multivariable regression.A total of 671 patients were tested [405 with suspected MOGAD, 99 with multiple sclerosis, 48 with AQP4-IgG-positive NMOSD and 119 with other neurological diseases (OND)] before treatment. In suspected MOGAD, 133 patients (33%) tested MOG-IgG-positive in serum and/or CSF; 94 (23%) double-positive (ADEM 36, CE 15, MY 8, NMOSD 9, ON 15 and Others 11); 17 (4.2%) serum-restricted-positive (ADEM 2, CE 0, MY 3, NMOSD 3, ON 5 and Others 4); and 22 (5.4%) CSF-restricted-positive (ADEM 3, CE 4, MY 6, NMOSD 2, ON 0 and Others 7). None of AQP4-IgG-positive NMOSD, multiple sclerosis or OND cases tested positive for MOG-IgGSERUM, but two with multiple sclerosis cases were MOG-IgGCSF-positive; the specificities of MOG-IgGSERUM and MOG-IgGCSF in suspected MOGAD were 100% [95% confidence interval (CI) 99–100%] and 99% (95% CI 97–100%), respectively. Unlike AQP4-IgG-positive NMOSD, the correlation between MOG-IgGSERUM and MOG-IgGCSF titres in MOGAD was weak. Multivariable regression analyses revealed MOG-IgGSERUM was associated with ON and ADEM, whereas MOG-IgGCSF was associated with ADEM and CE. The number needed to test for MOG-IgGCSF to diagnose one additional MOGAD case was 13.3 (14.3 for ADEM, 2 for CE, 19.5 for NMOSD, infinite for ON, 18.5 for MY and 6.1 for Others).In terms of MOG-IgGSERUM/CSF status, most cases were double-positive while including either serum-restricted (13%) or CSF-restricted (17%) cases. These statuses were independently associated with clinical phenotypes, especially in those with ON in serum and CE in CSF, suggesting pathophysiologic implications and the utility of preferential diagnostic testing. Further studies are warranted to deduce the clinical and pathological significance of compartmentalized MOG-IgG.
Glucocorticoid-driven mitochondrial damage stimulates Tau pathology
Authors: Du Fang , Yu Qing , Swerdlow Russell H , Waites Clarissa L 
Published: April 2023

Abstract
Prolonged exposure to glucocorticoids, the main stress hormones, damages the brain and is a risk factor for depression and Alzheimer's disease. Two major drivers of glucocorticoid-related neurotoxicity are mitochondrial dysfunction and Tau pathology; however, the molecular/cellular mechanisms precipitating these events, and their causal relationship, remain unclear.
Using cultured murine hippocampal neurons and 4–5-month-old mice treated with the synthetic glucocorticoid dexamethasone, we investigate the mechanisms underlying glucocorticoid-induced mitochondrial damage and Tau pathology.
We find that glucocorticoids stimulate opening of the mitochondrial permeability transition pore via transcriptional upregulation of its activating component, cyclophilin D. Inhibition of cyclophilin D is protective against glucocorticoid-induced mitochondrial damage as well as Tau phosphorylation and oligomerization in cultured neurons. We further identify the mitochondrially-targeted compound mito-apocynin as an inhibitor of glucocorticoid-induced permeability transition pore opening, and show that this compound protects against mitochondrial dysfunction, Tau pathology, synaptic loss, and behavioural deficits induced by glucocorticoids in vivo. Finally, we demonstrate that mito-apocynin and the glucocorticoid receptor antagonist mifepristone rescue Tau pathology in cytoplasmic hybrid cells, an ex vivo Alzheimer's disease model wherein endogenous mitochondria are replaced with mitochondria from Alzheimer's subjects.
These findings show that mitochondrial permeability transition pore opening is a precipitating factor in glucocorticoid-induced mitochondrial dysfunction, and that this event stimulates Tau pathogenesis. Our data also link glucocorticoids to mitochondrial dysfunction and Tau pathology in the context of Alzheimer's disease and suggest that mitochondria are promising therapeutic targets for mitigating stress- and Tau-related brain damage.
Secretory-IgA binding to intestinal microbiota attenuates inflammatory reactions as the intestinal barrier of preterm infants matures
Authors: Mahdally Sarah M , Izquierdo Mariana , Viscardi Rose M , Magder Laurence S , Crowley Helena M , Bafford Andrea C , Drachenberg Cinthia B , Farfan Mauricio J , Fasano Alessio , Sztein Marcelo B , Salerno-Goncalves Rosangela 
Published: April 2023

Abstract
Previous work has shown that Secretory-IgA (SIgA) binding to the intestinal microbiota is variable and may regulate host inflammatory bowel responses. Nevertheless, the impact of the SIgA functional binding to the microbiota remains largely unknown in preterm infants whose immature epithelial barriers make them particularly susceptible to inflammation. Here, we investigated SIgA binding to intestinal microbiota isolated from stools of preterm infants &lt;33 weeks gestation with various levels of intestinal permeability. We found that SIgA binding to intestinal microbiota attenuates inflammatory reactions in preterm infants. We also observed a significant correlation between SIgA affinity to the microbiota and the infant’s intestinal barrier maturation. Still, SIgA affinity was not associated with developing host defenses, such as the production of mucus and inflammatory calprotectin protein, but it depended on the microbiota shifts as the intestinal barrier matures. In conclusion, we reported an association between the SIgA functional binding to the microbiota and the maturity of the preterm infant’s intestinal barrier, indicating that the pattern of SIgA coating is altered as the intestinal barrier matures.
Plasmablasts in previously immunologically naïve COVID-19 patients express markers indicating mucosal homing and secrete antibodies cross-reacting with SARS-CoV-2 variants and other beta-coronaviruses
Authors: Lundgren Anna , Leach Susannah , Axelsson Hannes , Isakson Pauline , Nyström Kristina , Scharf Lydia , Andersson Bengt A , Miron Nicolae , Marklund Emelie , Andersson Lars-Magnus , Gisslén Magnus , Angeletti Davide , Bemark Mats 
Published: April 2023

Abstract
Antigen-specific class-switched antibodies are detected at the same time or even before IgM in serum of non-vaccinated individuals infected with SARS-CoV-2. These derive from the first wave of plasmablasts formed. Hence, the phenotype and specificity of plasmablasts can reveal information about early B-cell activation. Here we have analyzed B cells and plasmablasts circulating in blood of COVID-19 patients not previously exposed to SARS-CoV-2 during and after disease. We find that during infection with the original Wuhan strain, plasmablasts in blood produce IgA1, IgG1, and IgM, and that most express CCR10 and integrin β1, only some integrin β7, while the majority lack CCR9. Plasmablast-secreted antibodies are reactive to the spike (S) and nucleocapsid (N) proteins of the Wuhan strain as well as later variants of concern, but also bind S proteins from endemic and non-circulating betacoronaviruses. In contrast, after recovery, antibodies produced from memory B cells target variants of SARS-CoV-2 and SARS-CoV-1 but compared to previously non-infected individuals do not show increased binding to endemic coronaviruses. This suggests that the early antibody response to a large extent stems from pre-existing cross-reactive class-switched memory B cells, and that although newly formed memory cells target the novel SARS-CoV-2 virus the numbers of broadly cross-reactive memory B cells do not increase extensively. The observations give insight into the role of pre-existing memory B cells in early antibody responses to novel pathogens and may explain why class-switched antibodies are detected early in the serum of COVID-19 patients.
Automating the Deployment of Cyber Range with OpenStack
Authors: Zhou Shaohong , He Junjiang , Li Tao , Lan Xiaolong , Wang Yunpeng , Zhao Hui , Li Yihong 
Published: April 2023

Abstract
Cyber Range is an experimental platform based on virtualization technology to construct a controlled simulation environment, providing a real-world simulation environment for cybersecurity personnel to conduct various practical exercises. The problem is that generating a virtual environment satisfying the requirements is labor-intensive and time-consuming. To resolve the above problem, this paper proposes a system to automate the deployment of a cyber range. In our method, the first step is to collect virtual machines (VMs) related to cybersecurity and extract relevant features. Then, machine learning is used to classify VMs to reduce the cost of manual VMs selection. Lastly, leveraging the popular OpenStack cloud platform as the deployment platform enhances the applicability of the cyber range. When it comes time to deploy a virtual environment, the instructor only needs to provide some brief description information of a virtual environment. Then, the system will automatically parse the description file to complete the automated deployment of the virtual environment. This system has been successfully applied to the cyber range of Sichuan University for daily teaching tasks.
Results of the Eighth Scientific Workshop of ECCO: Pathophysiology and Risk Factors of Postoperative Crohn’s Disease Recurrence after an Ileocolonic Resection
Authors: Rivière Pauline , Bislenghi Gabriele , Hammoudi Nassim , Verstockt Bram , Brown Steven , Oliveira-Cunha Melissa , Bemelman Willem , Pellino Gianluca , Kotze Paulo Gustavo ,   the 8th Scientific Workshop of the European Crohn’s and Colitis Organisation, Dragoni Gabriele , Allocca Mariangela , Noor Nurulamin M , Pouillon Lieven , Mañosa Míriam , Savarino Edoardo , Allez Matthieu , Kapizioni Christina , Arebi Naila , Carvello Michele , De Vries Annemarie C , Domènech Eugeni , Myrelid Pär , Ferrante Marc , Panis Yves 
Published: April 2023

Abstract
Postoperative recurrence [POR] after an ileocolonic resection with ileocolonic anastomosis is frequently encountered in patients with Crohn’s disease. The 8th Scientific Workshop of ECCO reviewed the available evidence on the pathophysiology and risk factors for POR. In this paper, we discuss published data on the role of the microbiome, the mesentery, the immune system and the genetic background. In addition to investigating the causative mechanisms of POR, identification of risk factors is essential to tailor preventive strategies. Potential clinical, surgical and histological risk factors are presented along with their limitations. Emphasis is placed on unanswered research questions, guiding prevention of POR based on individual patient profiles.
A cost analysis of orthodontic space closure and implant treatment in patients missing maxillary lateral incisors with a long-term perspective
Authors: Hedmo Cecilia , Lindsten Rune , Josefsson Eva , Davidson Thomas 
Published: April 2023

Summary

Objective
Few studies within orthodontics present both economic and clinical findings. Missing maxillary lateral incisors is a frequently occurring anomaly. The treatment alternatives most used are orthodontic space closure and prosthetic replacement of the missing tooth. Our aim is to compare the total societal costs of orthodontic space closure (SC) and implant therapy (IT) in patients missing maxillary lateral incisors.

Methods
Records of 32 patients treated with SC (n = 18) or IT (n = 14) due to missing maxillary lateral incisors were retrieved from the archives. Direct costs and indirect costs in the short- and long-term were analysed using a cost analysis with a societal perspective up of to 12 years post-treatment.

Results
Comparing cases treated with SC and IT, the difference in direct short-term costs for treatment is €735.54, whereas SC is the least costly. There is no difference between SC and IT in short-term parent loss of productivity, long-term loss of productivity, costs for transportation, or direct long-term costs. A difference was found between SC and IT—in favour of SC—when comparing patients’ loss of productivity (P = 0.007), short-term societal costs (P &lt; 0.001), long-term societal costs (P = 0.037), and total societal costs (P &lt; 0.001).

Limitations
There is a limited number of patient records. Local factors such as subsidies, urban versus rural areas, taxes, etc. can influence monetary variables, so the transferability to other settings may be limited.

Conclusion
Patients treated with SC have a lower total societal cost compared to patients treated with IT. There was a difference in productivity loss for patients between SC and IT; however, concerning other indirect parameters and direct long-term costs, there was no difference between the two treatments.
Is ‘immigrant optimism’ in educational choice a problem? Ethnic gaps in Swedish upper secondary school completion
Authors: Dollmann Jörg , Jonsson Jan O , Mood Carina , Rudolphi Frida 
Published: April 2023

Abstract
In many Western countries, researchers have documented ambitious educational choices among students of immigrant origin, for example, the tendency to choose academically more demanding routes than others at given levels of school achievement (e.g. grades, GPA). While this may indicate integration, some warn against an ‘immigrant optimism trap’, because choosing more demanding tracks at lower levels of GPA may increase risks of non-completion. Using longitudinal Swedish population data (n ≈ 90,000), we estimate an upper secondary ‘ethnic completion gap’ of 12 per cent to the detriment of students of immigrant background. We then address the ‘trap hypothesis’ via two analyses. The first shows that if students of immigration background would make similar educational choices as other students at the same GPA, the completion gap would shrink by 3.4 percentage points. The second analysis, based on simulations, suggests that restricting admission to academic programmes based on prior GPA, would lead to a massive relocation of low- and mid-GPA students to—usually less demanding—vocational programmes, but would only reduce the completion gap by 2.2 percentage points. These changes must be considered marginal in view of the substantial restrictions of choice that either of these measures would entail. We conclude that completion gaps are not primarily a result of unfounded immigrant optimism, and that optimistic choices are likely to be a net positive for integration by improving the chances of immigrant youth to reach tertiary-level qualifications and professional occupations.
EHRA expert consensus document on the management of arrhythmias in frailty syndrome, endorsed by the Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), Latin America Heart Rhythm Society (LAHRS), and Cardiac Arrhythmia Society of Southern Africa (CASSA)
Authors: Savelieva Irina , Fumagalli Stefano , Kenny Rose Anne , Anker Stefan , Benetos Athanase , Boriani Giuseppe , Bunch Jared , Dagres Nikolaos , Dubner Sergio , Fauchier Laurent , Ferrucci Luigi , Israel Carsten , Kamel Hooman , Lane Deirdre A , Lip Gregory Y H , Marchionni Niccolò , Obel Israel , Okumura Ken , Olshansky Brian , Potpara Tatjana , Stiles Martin K , Tamargo Juan , Ungar Andrea , Kosiuk Jedrzej , Larsen Torben Bjerregaard , Dinov Borislav , Estner Heidi , Garcia Rodrigue , Moscoso Costa Francisco Manuel , Lampert Rachel , Lin Yenn-Jiang , Chin Ashley , Rodriguez Heliodoro Antonio , Strandberg Timo , Grodzicki Tomasz 
Published: April 2023

Abstract
There is an increasing proportion of the general population surviving to old age with significant chronic disease, multi-morbidity, and disability. The prevalence of pre-frail state and frailty syndrome increases exponentially with advancing age and is associated with greater morbidity, disability, hospitalization, institutionalization, mortality, and health care resource use. Frailty represents a global problem, making early identification, evaluation, and treatment to prevent the cascade of events leading from functional decline to disability and death, one of the challenges of geriatric and general medicine. Cardiac arrhythmias are common in advancing age, chronic illness, and frailty and include a broad spectrum of rhythm and conduction abnormalities. However, no systematic studies or recommendations on the management of arrhythmias are available specifically for the elderly and frail population, and the uptake of many effective antiarrhythmic therapies in these patients remains the slowest. This European Heart Rhythm Association (EHRA) consensus document focuses on the biology of frailty, common comorbidities, and methods of assessing frailty, in respect to a specific issue of arrhythmias and conduction disease, provide evidence base advice on the management of arrhythmias in patients with frailty syndrome, and identifies knowledge gaps and directions for future research.
Computer-aided design of a cyclic di-AMP synthesizing enzyme CdaA inhibitor
Authors: Neumann Piotr , Kloskowski Patrick , Ficner Ralf 
Published: April 2023

AbstractCyclic di-AMP (c-di-AMP) is an essential secondary messenger regulating cell wall homeostasis and myriads of physiological processes in several Gram-positive and mycobacteria, including human pathogens. Hence, c-di-AMP synthesizing enzymes (DACs) have become a promising antibacterial drug target. To overcome a scarcity of small molecule inhibitors of c-di-AMP synthesizing enzyme CdaA, a computer-aided design of a new compound that should block the enzyme has been performed. This has led to the identification of a molecule comprising two thiazole rings and showing inhibitory potential based on ITC measurements. Thiazole scaffold is a good pharmacophore nucleus known due to its various pharmaceutical applications. It is contained in more than 18 FDA-approved drugs as well as in dozens of experimental drugs. Hence, the designed inhibitor can serve as a potent lead compound for further development of inhibitor against CdaA.
Differentially Expressed Genes Associated with Body Size Changes and Transposable Element Insertions between Caenorhabditis elegans and Its Sister Species, Caenorhabditis inopinata
Authors: Kawahara Kazuma , Inada Taruho , Tanaka Ryusei , Dayi Mehmet , Makino Takashi , Maruyama Shinichiro , Kikuchi Taisei , Sugimoto Asako , Kawata Masakado 
Published: April 2023

Abstract
Why the recently discovered nematode Caenorhabditis inopinata differs so greatly from its sibling species Caenorhabditis elegans remains unknown. A previous study showed that C. inopinata has more transposable elements (TEs), sequences that replicate and move autonomously throughout the genome, potentially altering the expression of neighboring genes. In this study, we focused on how the body size of this species has evolved and whether TEs could affect the expression of genes related to species-specific traits such as body size. First, we compared gene expression levels between C. inopinata and C. elegans in the L4 larval and young adult stages—when growth rates differ most prominently between these species—to identify candidate genes contributing to their differences. The results showed that the expression levels of collagen genes were consistently higher in C. inopinata than in C. elegans and that some genes related to cell size were differentially expressed between the species. Then, we examined whether genes with TE insertions are differentially expressed between species. Indeed, the genes featuring C. inopinata-specific TE insertions had higher expression levels in C. inopinata than in C. elegans. These upregulated genes included those related to body size, suggesting that these genes could be candidates for artificial TE insertion to examine the role of TEs in the body size evolution of C. inopinata.
Genomic determination of breeding systems and trans-specific evolution of HD MAT genes in suilloid fungi
Authors: Ke Yi-Hong , Branco Sara , Bazzicalupo Anna L , Nguyen Nhu H , Liao Hui-Ling , Kennedy Peter , Bruns Thomas D , Kuo Alan , LaButti Kurt , Barry Kerrie , Grigoriev Igor , Vilgalys Rytas 
Published: April 2023

Abstract
Studying the signatures of evolution can help to understand genetic processes. Here, we demonstrate how the existence of balancing selection can be used to identify the breeding systems of fungi from genomic data. The breeding systems of fungi are controlled by self-incompatibility loci that determine mating types between potential mating partners, resulting in strong balancing selection at the loci. Within the fungal phylum Basidiomycota, two such self-incompatibility loci, namely HD MAT locus and P/R MAT locus, control mating types of gametes. Loss of function at one or both MAT loci results in different breeding systems and relaxes the MAT locus from balancing selection. By investigating the signatures of balancing selection at MAT loci, one can infer a species’ breeding system without culture-based studies. Nevertheless, the extreme sequence divergence among MAT alleles imposes challenges for retrieving full variants from both alleles when using the conventional read-mapping method. Therefore, we employed a combination of read-mapping and local de novo assembly to construct haplotypes of HD MAT alleles from genomes in suilloid fungi (genera Suillus and Rhizopogon). Genealogy and pairwise divergence of HD MAT alleles showed that the origins of mating types predate the split between these two closely related genera. High sequence divergence, trans-specific polymorphism, and the deeply diverging genealogy confirm the long-term functionality and multiallelic status of HD MAT locus in suilloid fungi. This work highlights a genomics approach to studying breeding systems regardless of the culturability of organisms based on the interplay between evolution and genetics.