bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune responses during COVID-19 breakthrough cases in vaccinated children and adolescents
Authors: Rivera-Pérez Daniela , Méndez Constanza , Diethelm-Varela Benjamín , Melo-González Felipe , Vázquez Yaneisi , Meng Xing , Xin Qianqian , Fasce Rodrigo A. , Fernández Jorge , Mora Judith , Ramirez Eugenio , Acevedo Mónica L. , Valiente-Echeverría Fernando , Soto-Rifo Ricardo , Grifoni Alba , Weiskopf Daniela , Sette Alessandro , Astudillo Patricio , Le Corre Nicole , Abarca Katia , Perret Cecilia , González Pablo A. , Soto Jorge A. , Bueno Susan M. , Kalergis Alexis M. 
Published: May 2024

BackgroundVaccine effectiveness against SARS-CoV-2 infection has been somewhat limited due to the widespread dissemination of the Omicron variant, its subvariants, and the immune response dynamics of the naturally infected with the virus.MethodsTwelve subjects between 3-17 years old (yo), vaccinated with two doses of CoronaVac®, were followed and diagnosed as breakthrough cases starting 14 days after receiving the second dose. Total IgGs against different SARS-CoV-2 proteins and the neutralizing capacity of these antibodies after infection were measured in plasma. The activation of CD4+ and CD8+ T cells was evaluated in peripheral blood mononuclear cells stimulated with peptides derived from the proteins from the wild-type (WT) virus and Omicron subvariants by flow cytometry, as well as different cytokines secretion by a Multiplex assay.Results2 to 8 weeks post-infection, compared to 4 weeks after 2nd dose of vaccine, there was a 146.5-fold increase in neutralizing antibody titers against Omicron and a 38.7-fold increase against WT SARS-CoV-2. Subjects showed an increase in total IgG levels against the S1, N, M, and NSP8 proteins of the WT virus. Activated CD4+ T cells showed a significant increase in response to the BA.2 subvariant (p&lt;0.001). Finally, the secretion of IL-2 and IFN-γ cytokines showed a discreet decrease trend after infection in some subjects.ConclusionSARS-CoV-2 infection in the pediatric population vaccinated with an inactivated SARS-CoV-2 vaccine produced an increase in neutralizing antibodies against Omicron and increased specific IgG antibodies for different SARS-CoV-2 proteins. CD4+ T cell activation was also increased, suggesting a conserved cellular response against the Omicron subvariants, whereas Th1-type cytokine secretion tended to decrease.Clinical Trial Registrationclinicaltrials.gov #NCT04992260
MCP-3 as a prognostic biomarker for severe fever with thrombocytopenia syndrome: a longitudinal cytokine profile study
Authors: Liu Zishuai , Zhao Chenxi , Yu Hong , Zhang Rongling , Xue Xiaoyu , Jiang Zhouling , Ge Ziruo , Xu Yanli , Zhang Wei , Lin Ling , Chen Zhihai 
Published: May 2024

IntroductionSevere fever with thrombocytopenia syndrome (SFTS) is characterized by a high mortality rate and is associated with immune dysregulation. Cytokine storms may play an important role in adverse disease regression, this study aimed to assess the validity of MCP-3 in predicting adverse outcomes in SFTS patients and to investigate the longitudinal cytokine profile in SFTS patients.MethodsThe prospective study was conducted at Yantai Qishan Hospital from May to November 2022. We collected clinical data and serial blood samples during hospitalization, patients with SFTS were divided into survival and non-survival groups based on the clinical prognosis.ResultsThe levels of serum 48 cytokines were measured using Luminex assays. Compared to healthy controls, SFTS patients exhibited higher levels of most cytokines. The non-survival group had significantly higher levels of 32 cytokines compared to the survival group. Among these cytokines, MCP-3 was ranked as the most significant variable by the random forest (RF) model in predicting the poor prognosis of SFTS patients. Additionally, we validated the predictive effects of MCP-3 through receiver operating characteristic (ROC) curve analysis with an AUC of 0.882 (95% CI, 0.787-0.978, P &lt;0.001), and the clinical applicability of MCP-3 was assessed favorably based on decision curve analysis (DCA). The Spearman correlation analysis indicated that the level of MCP-3 was positively correlated with ALT, AST, LDH, α-HBDH, APTT, D-dimer, and viral load (P&lt;0.01).DiscussionFor the first time, our study identified and validated that MCP-3 could serve as a meaningful biomarker for predicting the fatal outcome of SFTS patients. The longitudinal cytokine profile analyzed that abnormally increased cytokines were associated with the poor prognosis of SFTS patients. Our study provides new insights into exploring the pathogenesis of cytokines with organ damage and leading to adverse effects.
Influence of sports on cortical excitability in patients with spinal cord injury: a TMS study
Authors: Frey Vanessa N. , Langthaler Patrick B. , Renz Nora , Zimmermann Georg , Höhn Christopher , Schwenker Kerstin , Thomschewski Aljoscha , Kunz Alexander B. , Höller Yvonne , Nardone Raffaele , Trinka Eugen 
Published: May 2024

BackgroundPatients with spinal cord injury (SCI) show abnormal cortical excitability that might be caused by deafferentation. We hypothesize a reduced short-interval intracortical inhibition preceding movement in patients with SCI compared with healthy participants. In addition, we expect that neuroplasticity induced by different types of sports can modulate intracortical inhibition during movement preparation in patients with SCI.MethodsWe used a reaction test and paired-pulse transcranial magnetic stimulation to record cortical excitability, assessed by measuring amplitudes of motor-evoked potentials in preparation of movement. The participants were grouped as patients with SCI practicing wheelchair dancing (n = 7), other sports (n = 6), no sports (n = 9), and healthy controls (n = 24).ResultsThere were neither significant differences between healthy participants and the patients nor between the different patient groups. A non-significant trend (p = .238), showed that patients engaged in sports have a stronger increase in cortical excitability compared with patients of the non-sportive group, while the patients in the other sports group expressed the highest increase in cortical excitability.ConclusionThe small sample sizes limit the statistical power of the study, but the trending effect warrants further investigation of different sports on the neuroplasticity in patients with SCI. It is not clear how neuroplastic changes impact the sensorimotor output of the affected extremities in a patient. This needs to be followed up in further studies with a greater sample size.
Establishment of a reverse transcription–recombinase polymerase amplification–lateral flow dipstick method for the dual detection of Israeli acute paralysis virus and chronic bee paralysis virus
Authors: Sun Li , Cheng Yu , Fei Dongliang , Ma Yueyu , Ma Mingxiao , Li Ming 
Published: May 2024

IntroductionAs an important social insect, honey bees play crucial roles in agricultural production, sustainable development of agricultural production, and the balance of the natural environment. However, in recent years, Israeli acute paralysis virus (IAPV) and chronic bee paralysis virus (CBPV), the main pathogens of bee paralysis, have continuously harmed bee colonies and caused certain losses to the beekeeping industry. Some beekeeping farms are located in wild or remote mountainous areas, and samples from these farms cannot be sent to the laboratory for testing in a timely manner, thereby limiting the accurate and rapid diagnosis of the disease.Methods and resultsIn this study, we used a reverse transcription–recombinase polymerase amplification–lateral flow dipstick (RT–RPA–LFD) method for the dual detection of IAPV and CBPV. RPA primers and LFD detection probes were designed separately for their conserved genes. Primers and probes were screened, and the forward and reverse primer ratios, reaction times, and temperatures were optimized. According to the results of the optimization tests, the optimal reaction temperature for RT–RPA is 37°C, and when combined with LFD, detection with the naked eye requires &lt;20 min. The developed RPA–LFD method specifically targets IAPV and CBPV and has no cross-reactivity with other common bee viruses. In addition, the minimum detection limit of the RT–RPA–LFD method is 101 copies/μL.ConclusionBased this study, this method is suitable for the detection of clinical samples and can be used for field detection of IAPV and CBPV.
Genetic and virulence characteristics of hybrid Shiga toxin-producing and atypical enteropathogenic Escherichia coli strains isolated in South Korea
Authors: Lee Woojung , Ha Jina , Choi Jaehyun , Jung Yewon , Kim Eiseul , An Eun Sook , Kim Seung Hwan , Shin Hakdong , Ryu Sangryeol , Kim Soon Han , Kim Hae-Yeong 
Published: May 2024

IntroductionThe predominant hybrid pathogenic E. coli, enterohemorrhagic E. coli (EHEC), combines characteristics of Shiga toxin-producing E. coli (STEC) and enteropathogenic E. coli (EPEC), contributing to global outbreaks with severe symptoms including fatal consequences. Since EHEC infection was designated as a notifiable disease in 2000 in South Korea, around 2000 cases have been reported, averaging approximately 90 cases annually.AimIn this work, genome-based characteristic analysis and cell-based assay of hybrid STEC/aEPEC strains isolated from livestock feces, animal source foods, and water in South Korea was performed.MethodsTo identify the virulence and antimicrobial resistance genes, determining the phylogenetic position of hybrid STEC/aEPEC strains isolated in South Korea, a combination of real-time PCR and whole-genome sequencing (WGS) was used. Additionally, to assess the virulence of the hybrid strains and compare them with genomic characterization, we performed a cell cytotoxicity and invasion assays.ResultsThe hybrid STEC/aEPEC strains harbored stx and eae genes, encoding Shiga toxins and E. coli attachment/effacement related protein of STEC and EPEC, respectively. Furthermore, all hybrid strains harbored plasmid-carried enterohemolysin(ehxCABD), a key virulence factor in prevalent pathogenic E. coli infections, such as diarrheal disease and hemolytic-uremic syndrome (HUS). Genome-wide phylogenetic analysis revealed a close association between all hybrid strains and specific EPEC strains, suggesting the potential acquisition of Stx phages during STEC/aEPEC hybrid formation. Some hybrid strains showed cytotoxic activity against HeLa cells and invasive properties against epithelial cells. Notably, all STEC/aEPEC hybrids with sequence type (ST) 1,034 (n = 11) exhibited higher invasiveness than those with E2348/69. This highlights the importance of investigating potential correlations between STs and virulence characteristics of E. coli hybrid strains.ConclusionThrough genome-based characterization, we confirmed that the hybrid STEC/aEPEC strains are likely EPEC strains that have acquired STEC virulence genes via phage. Furthermore, our results emphasize the potential increased danger to humans posed by hybrid STEC/aEPEC strains isolated in South Korea, containing both stx and eaeA, compared to STEC or EPEC alone.
Seeing beyond the symptoms: biomarkers and brain regions linked to cognitive decline in Alzheimer’s disease
Authors: Hojjati Seyed Hani , Babajani-Feremi Abbas ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: May 2024

ObjectiveEarly Alzheimer’s disease (AD) diagnosis remains challenging, necessitating specific biomarkers for timely detection. This study aimed to identify such biomarkers and explore their associations with cognitive decline.MethodsA cohort of 1759 individuals across cognitive aging stages, including healthy controls (HC), mild cognitive impairment (MCI), and AD, was examined. Utilizing nine biomarkers from structural MRI (sMRI), diffusion tensor imaging (DTI), and positron emission tomography (PET), predictions were made for Mini-Mental State Examination (MMSE), Clinical Dementia Rating Scale Sum of Boxes (CDRSB), and Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS). Biomarkers included four sMRI (e.g., average thickness [ATH]), four DTI (e.g., mean diffusivity [MD]), and one PET Amyloid-β (Aβ) measure. Ensemble regression tree (ERT) technique with bagging and random forest approaches were applied in four groups (HC/MCI, HC/AD, MCI/AD, and HC/MCI/AD).ResultsAβ emerged as a robust predictor of cognitive scores, particularly in late-stage AD. Volumetric measures, notably ATH, consistently correlated with cognitive scores across early and late disease stages. Additionally, ADAS demonstrated links to various neuroimaging biomarkers in all subject groups, highlighting its efficacy in monitoring brain changes throughout disease progression. ERT identified key brain regions associated with cognitive scores, such as the right transverse temporal region for Aβ, left and right entorhinal cortex, left inferior temporal gyrus, and left middle temporal gyrus for ATH, and the left uncinate fasciculus for MD.ConclusionThis study underscores the importance of an interdisciplinary approach in understanding AD mechanisms, offering potential contributions to early biomarker development.
Alzheimer’s disease and oral manifestations: a bi-directional Mendelian randomization study
Authors: Huang Jingxuan , Deng Aiping , Bai Yunshuang , Li Chunyu , Shang Huifang 
Published: May 2024

BackgroundEpidemiological studies have provided evidence suggesting an association between Alzheimer’s disease (AD) and various oral manifestations. However, conflicting conclusions have been drawn, and whether a causal association truly exists remains unclear.MethodsIn order to investigate the potential causal association between AD and prevalent oral diseases, we conducted a bi-directional two-sample Mendelian randomization analysis based on summary statistics from genome-wide association studies of AD (N = 63,926), as well as mouth ulcer (N = 461,103), oral cavity cancer (N = 4,151), and periodontal disease (N = 527,652).ResultsWe identified that one standard increase in the risk of AD was causally associated with a reduced risk of oral cavity cancer (OR = 0.76, 95% CI: 0.63–0.92, p = 3.73 × 10−3). In the opposite direction, oral conditions were not causally associated with risk of AD.ConclusionThe present findings contributed to a better understanding of the correlation between AD and oral conditions, specifically oral cavity cancer. These results also identified new avenues for exploring the underlying mechanisms of oral cavity cancer.
Comparison of two automated CT perfusion software packages in patients with ischemic stroke presenting within 24 h of onset
Authors: Kim Nakhoon , Ha Sue Young , Park Gi-Hun , Park Jong-Hyeok , Kim Dongmin , Sunwoo Leonard , Kye Min-Surk , Baik Sung Hyun , Jung Cheolkyu , Ryu Wi-Sun , Kim Beom Joon 
Published: May 2024

BackgroundWe compared the ischemic core and hypoperfused tissue volumes estimated by RAPID and JLK-CTP, a newly developed automated computed tomography perfusion (CTP) analysis package. We also assessed agreement between ischemic core volumes by two software packages against early follow-up infarct volumes on diffusion-weighted images (DWI).MethodsThis retrospective study analyzed 327 patients admitted to a single stroke center in Korea from January 2021 to May 2023, who underwent CTP scans within 24 h of onset. The concordance correlation coefficient (ρ) and Bland–Altman plots were utilized to compare the volumes of ischemic core and hypoperfused tissue volumes between the software packages. Agreement with early (within 3 h from CTP) follow-up infarct volumes on diffusion-weighted imaging (n = 217) was also evaluated.ResultsThe mean age was 70.7 ± 13.0 and 137 (41.9%) were female. Ischemic core volumes by JLK-CTP and RAPID at the threshold of relative cerebral blood flow (rCBF) &lt; 30% showed excellent agreement (ρ = 0.958 [95% CI, 0.949 to 0.966]). Excellent agreement was also observed for time to a maximum of the residue function (Tmax) &gt; 6 s between JLK-CTP and RAPID (ρ = 0.835 [95% CI, 0.806 to 0.863]). Although early follow-up infarct volume showed substantial agreement in both packages (JLK-CTP, ρ = 0.751 and RAPID, ρ = 0.632), ischemic core volumes at the threshold of rCBF &lt;30% tended to overestimate ischemic core volumes.ConclusionJLK-CTP and RAPID demonstrated remarkable concordance in estimating the volumes of the ischemic core and hypoperfused area based on CTP within 24 h from onset.
Neuroligin-1 dependent phosphotyrosine signaling in excitatory synapse differentiation
Authors: Szíber Zsófia , Drouet Adèle , Mondin Magali , Levet Florian , Thoumine Olivier 
Published: May 2024

IntroductionThe synaptic adhesion molecule neuroligin-1 (NLGN1) is involved in the differentiation of excitatory synapses, but the precise underlying molecular mechanisms are still debated. Here, we explored the role of NLGN1 tyrosine phosphorylation in this process, focusing on a subset of receptor tyrosine kinases (RTKs), namely FGFR1 and Trks, that were previously described to phosphorylate NLGN1 at a unique intracellular residue (Y782).MethodsWe used pharmacological inhibitors and genetic manipulation of those RTKs in dissociated hippocampal neurons, followed by biochemical measurement of NLGN1 phosphorylation and immunocytochemical staining of excitatory synaptic scaffolds.ResultsThis study shows that: (i) the accumulation of PSD-95 at de novo NLGN1 clusters induced by neurexin crosslinking is reduced by FGFR and Trk inhibitors; (ii) the increase in PSD-95 puncta caused by NLGN1 over-expression is impaired by FGFR and Trk inhibitors; (iii) TrkB activation by BDNF increases NLGN1 phosphorylation; and (iv) TrkB knock-down impairs the increase of PSD-95 puncta caused by NLGN1 over-expression, an effect which is not seen with the NLGN1 Y782A mutant.DiscussionTogether, our data identify TrkB as one of the major RTKs responsible for NLGN1 tyrosine phosphorylation, and reveal that TrkB activity is necessary for the synaptogenic effects of NLGN1.
Collagen-derived dipeptide prolyl-hydroxyproline cooperates with Foxg1 to activate the PGC-1α promoter and induce brown adipocyte-like phenotype in rosiglitazone-treated C3H10T1/2 cells
Authors: Nomura Kaho , Kimira Yoshifumi , Kobayashi Ryosuke , Shiobara Yuna , Osawa Yoshihiro , Kataoka-Matsushita Aya , Shimizu Jun , Wada Masahiro , Mano Hiroshi 
Published: May 2024

BackgroundThe global obesity epidemic is a significant public health issue, often leading to metabolic disorders such as diabetes and cardiovascular diseases. Collagen peptides (CP) and their bioactive component, Prolyl-hydroxyproline (Pro-Hyp), have shown potential in reducing adipocyte size, with unclear mechanisms concerning brown adipocyte differentiation.MethodsWe investigated the effects of Pro-Hyp on the differentiation of brown adipocytes in C3H10T1/2 mesenchymal stem cells, focusing on its impact on adipocyte size, gene expression related to brown fat function, and mitochondrial activity.ResultsPro-Hyp treatment decreased adipocyte size and upregulated brown fat-specific genes, including C/EBPα, PGC-1α, and UCP-1. Remarkably, it did not alter PPARγ expression. Pro-Hyp also elevated mitochondrial activity, suggesting enhanced brown adipocyte functionality. A Pro-Hyp responsive element was identified in the PGC-1α gene promoter, which facilitated the binding of the Foxg1 transcription factor, indicating a novel regulatory mechanism.ConclusionPro-Hyp promotes brown adipocyte differentiation, potentially offering a therapeutic strategy for obesity management. This study provides a molecular basis for the anti-obesity effects of CP, although further in vivo studies are needed to confirm these findings and to investigate the potential impact on beige adipocyte differentiation.
Development of a screener to assess athlete risk behavior of not using third-party tested nutritional supplements
Authors: Wardenaar Floris C. , Schott Kinta D. , Seltzer Ryan G. N. , Gardner Christopher D. 
Published: May 2024

IntroductionThe aim of this cross-sectional study was to develop an algorithm to predict athletes use of third-party tested (TPT) supplements. Therefore, a nutritional supplement questionnaire was used with a section about self-reported TPT supplement use.MethodsOutcomes were randomly assigned to a training dataset to identify predictors using logistic regression models, or a cross-validation dataset. Training data were used to develop an algorithm with a score from 0 to 100 predicting use or non-use of TPT nutritional supplements.ResultsA total of n = 410 NCAA Division I student-athletes (age: 21.4 ± 1.6 years, 53% female, from &gt;20 sports) were included. Then n = 320 were randomly selected, of which 34% (n = 109) of users consistently reported that all supplements they used were TPT. Analyses resulted in a 10-item algorithm associated with use or non-use of TPT. Risk quadrants provided the best fit for classifying low vs. high risk toward inconsistent TPT-use resulting in a cut-off ≥60% (χ2(4) = 61.26, P &lt; 0.001), with reasonable AUC 0.78. There was a significant association for TPT use (yes/no) and risk behavior (low vs. high) defined from the algorithm (χ2(1)=58.6, P &lt; 0.001). The algorithm had a high sensitivity, classifying 89% of non-TPT users correctly, while having a low specificity, classifying 49% of TPT-users correctly. This was confirmed by cross-validation (n = 34), reporting a high sensitivity (83%), despite a lower AUC (0.61).DiscussionThe algorithm classifies high-risk inconsistent TPT-users with reasonable accuracy, but lacks the specificity to classify consistent users at low risk. This approach should be useful in identifying athletes that would benefit from additional counseling.