bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of an immunoassay for the simultaneous detection of GADA and ZnT8A in autoimmune diabetes using a ZnT8/GAD65 chimeric molecule
Authors: Trabucchi Aldana , Bombicino Silvina Sonia , Sabljic Adriana Victoria , Marfía Juan Ignacio , Targovnik Alexandra Marisa , Iacono Rubén Francisco , Miranda María Victoria , Valdez Silvina Noemí 
Published: August 2023

IntroductionThe combined presence of autoantibodies to the 65 kDa isoform of glutamic acid decarboxylase (GADA) and to the islet-specific cation efflux transporter ZnT8 (ZnT8A) in serum is the best predictive sign of the loss of immune tolerance and the clinical manifestation of autoimmune diabetes mellitus (DM). The screening of GADA and ZnT8A could help to reach to a correct diagnosis and to start an early and adequate treatment. The aim of the study was to develop an immunoassay for the simultaneous detection of these autoantibodies using a chimera molecule that includes the immunodominant regions of ZnT8 and GAD65, expressed by baculovirus-insect cells system.Materials and MethodsZnT8/GAD65 was expressed using the Bac to Bac™ baculovirus expression system. The recombinant chimera was purified by an His6-tag and identified by SDS-PAGE and western blot analysis, and by an indirect ELISA using specific antibodies against ZnT8 and GAD65. A fraction of ZnT8/GAD65 was biotinylated. A bridge ELISA (b-ELISA) was developed using ZnT8/GAD65 immobilized in polystyrene microplates, human sera samples from healthy individuals (n = 51) and diabetic patients (n = 49) were then incubated, and afterwards ZnT8/GAD65-biotin was added. Immune complexes were revealed with Streptavidin-Horseradish Peroxidase. Results were calculated as specific absorbance and expressed as standard deviation scores: SDs.ResultsZnT8/GAD65 was efficiently produced, yielding 30 mg/L culture medium, 80% pure. This recombinant chimera retains the immunoreactive conformation of the epitopes that are recognized by their specific antibodies, so it was used for the development of a high sensitivity (75.51%) and specificity (98.04%) b-ELISA for the detection of ZnT8A and/or GADA, in a one-step screening assay. The ROC curves demonstrated that this method had high accuracy to distinguish between samples from healthy individuals and diabetic patients (AUC = 0.9488); the cut-off value was stablished at 2 SDs.ConclusionsThis immunoassay is useful either to confirm autoimmune diabetes or for detection in routine screening of individuals at risk of autoimmune DM. As DM is a slow progress disease, remaining asymptomatic for a long preclinical period, serological testing is of importance to establish a preventive treatment.
Antibodies to leukotoxin A from the periodontal pathogen Aggregatibacter actinomycetemcomitans in patients at an increased risk of rheumatoid arthritis
Authors: Martinsson Klara , Di Matteo Andrea , Öhman Carina , Johansson Anders , Svärd Anna , Mankia Kulveer , Emery Paul , Kastbom Alf 
Published: August 2023

ObjectivesPeriodontitis and underlying bacteria have been linked to the development of rheumatoid arthritis (RA). One suggested pathogen is Aggregatibacter actinomycetemcomitans (A.a.), which expresses leukotoxin A (LtxA) that can citrullinate human proteins, providing a possible trigger for the production of anti-citrullinated protein antibodies (ACPA). In this study, we seek to determine the presence of antibodies toward LtxA in patients at risk of developing RA.MethodsTwo prospective observational patient cohorts (one Swedish and one British) with symptomatic at-risk patients were studied. Anti-LtxA antibodies were analyzed by a cell-based neutralization assay in baseline serum and compared to 100 Swedish blood donors that served as controls.ResultsSerum anti-LtxA levels or positivity did not differ between patients and blood donors. In the British cohort, anti-LtxA was more prevalent among ACPA-positive arthralgia patients compared with ACPA-negative arthralgia cases (24% vs. 13%, p &lt; 0.0001). In the Swedish at-risk cohort, anti-LtxA positive patients were at increased risk of progression to arthritis (hazard ratio (HR) 2.10, 95% CI 1.04–4.20), but this was not confirmed in the UK at-risk cohort (HR 0.99, CI 0.60–1.65).ConclusionSerum anti-LtxA is not elevated before RA diagnosis, and associations with disease progression and ACPA levels differ between populations. Other features of the oral microbiome should be explored in upcoming periodontitis-related RA research.
Use of social media for the improvement of safety knowledge and awareness among Saudi Arabian phlebotomists
Authors: Attar Razaz , Almohanna Asmaa , Almusharraf Ahlam , Alhazmi Amal , Alanzi Nouf , Al-Anezi Fahad , Alanzi Turki , Sroor Raghad , Albishri Ahmed , Alzahrani Amwaj , Alsabilah Taif , Alkenani Ali , Alghamdi Raghad , AlGethami Fai , AlGethami Arub 
Published: August 2023

PurposeThe purpose of this study is to investigate the use of social media for the improvement of safety knowledge and awareness among phlebotomists.MethodsAs this study was intended to arrive at specific conclusions using empirical evidence, a deductive quantitative cross-sectional online survey design was adopted. A total of 521 phlebotomists participated in the survey, and 86 incomplete responders were removed, resulting in a final sample of 435 considered in this study. T-tests and ANOVA were used to analyze the data.ResultsA total of 41.6% stated that social media was very effective, and 31.5% stated that it was somewhat effective in improving safety knowledge and awareness. in addition, this study revealed no major differences between male and female participants (p &gt; 0.05) with respect to the effectiveness of social media. However, statistically significant differences (p &lt; 0.05) among the age groups were identified in relation to the effectiveness of social media and the intention to use it in the future.ConclusionSocial media applications are effective for knowledge dissemination among healthcare professionals.
Drug-eluting beads bronchial arterial chemoembolization vs. conventional bronchial arterial chemoembolization in the treatment of advanced non-small cell lung cancer
Authors: Yu Guocan , Shen Yanqin , Chen Liangliang , Xu Xudong , Yang Jun 
Published: August 2023

PurposeTo compare the effectiveness and safety of drug-eluting bead bronchial artery chemoembolization (DEB-BACE) with conventional bronchial artery chemoembolization (cBACE) and provide a novel treatment option for advanced non-small cell lung cancer (NSCLC).MethodsPatients with advanced NSCLC underwent DEB-BACE or cBACE and were screened retrospectively. Progression-free survival (PFS) and overall survival (OS) were the primary outcome indicators, while technical success rate, objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were the secondary ones.ResultsA total of 41 patients were enrolled in the study, 12 in the DEB-BACE group and 29 in the cBACE group, according to the treatment regimen. No patient achieved complete response. Eighteen patients achieved partial response (9 in each group), 15 patients achieved stable disease (3 in the DEB-BACE group and 12 in the cBACE group), and eight patients achieved progressive disease (all in the cBACE group) when treated for 2 months. The overall ORR and DCR were 43.9% (18/41) and 80.5% (33/41), respectively. ORR and DCR in the DEB-BACE group were 50.0% (9/12) and 100.0% (12/12), respectively, while ORR and DCR in the cBACE group were 31.0% (9/29) and 72.4% (21/29), respectively. Compared to cBACE, the ORR and DCR of DEB-BACE were significantly improved (p &lt; 0.05). The median PFS was better in the DEB-BACE group than in the cBACE group (6.95 months vs. 3.20 months, respectively, Hazard Ratio [HR] = 0.416; p = 0.005). Furthermore, the median OS was significantly better in the DEB-BACE group than in the cBACE group (28.5 months vs. 22.5 months, respectively, HR = 0.316; p = 0.020).ConclusionDEB-BACE has a good safety and therapeutic profile in advanced NSCLC and is superior to cBACE. DEB-BACE can be used as an alternative treatment option for advanced NSCLC, even in elderly patients.
Differential expression analysis of miRNAs in macrophage-derived exosomes in the tuberculosis-infected bone microenvironment
Authors: Sun Zhicheng , Pang Xiaoyang , Wang Xiyang , Zeng Hao 
Published: August 2023

BackgroundMacrophages play an important role in regulating the course of spinal tuberculosis within the bone microenvironment. This study aimed to investigate the differential expression of miRNA in macrophage-derived exosomes within the tuberculosis-infected bone microenvironment, to identify miRNAs that hold potential as diagnostic markers and therapeutic targets.MethodsWe established study cohorts for spinal tuberculosis, collected bone marrow blood samples, isolated macrophage exosomes, and performed exosome miRNA sequencing. A miRNA-mRNA co-expression network was constructed using WGCNA analysis. Gene GO analysis and KEGG pathway enrichment analysis were performed using KOBAS software. Target miRNAs were selected based on fold change, P-value, and false discovery rate, and their validation was carried out using qRT-PCR and ROC curve studies. Subsequently, we constructed a target gene network for these miRNAs and performed KEGG pathway enrichment analysis to explore the potential signaling mechanisms involved in regulating the disease course of spinal tuberculosis.ResultsOur findings revealed that macrophages from the tuberculosis-infected bone microenvironment exhibited an M1 phenotype. The successful extraction of exosomes from macrophage supernatants was confirmed through electron microscopy, particle size analysis, and protein blot analysis. Exosome miRNA-seq demonstrated that 28 miRNAs were up-regulated, while 34 miRNAs were down-regulated in individuals with spinal tuberculosis. GO analysis and KEGG pathway enrichment analysis indicated that the differentially expressed miRNAs were involved in various biological processes, cell components, molecular functions, and signaling pathways, which collectively contribute to the regulation of the disease course of spinal tuberculosis. Notably, miRNA-125b-5p was successfully selected based on fold change, p-value, and false discovery rate. qRT-PCR validation further confirmed the significant up-regulation of miRNA-125b-5p in spinal tuberculosis. The ROC curve revealed that miR-125b-5p is a potential diagnostic biomarker for spinal tuberculosis. Moreover, construction of the miRNA-125b-5p target gene network and subsequent KEGG enrichment analysis highlighted the importance of MAPK, TNF, Ras, Rap1, and the PI3K-Akt signaling pathways in the regulation of the disease course of spinal tuberculosis.ConclusionOur study demonstrates differential expression of miRNAs in macrophage-derived exosomes in the tuberculosis-infected bone microenvironment. Specifically, MiRNA-125b-5p is significantly up-regulated in spinal tuberculosis and shows potential as a diagnostic biomarker for spinal tuberculosis.
Wildtype peers rescue social play and 50-kHz ultrasonic vocalization deficits in juvenile female Cacna1c heterozygous rats
Authors: Bogdan Rebecca , Kayumova Rukhshona , Schwarting Rainer K. W. , Wöhr Markus , Kisko Theresa M. 
Published: August 2023

BackgroundHealthy brain development depends on early social practices and experiences. The risk gene CACNA1C is implicated in numerous neuropsychiatric disorders, in which key characteristics include deficits in social functioning and communication. Recently, we reported sex-dependent impairments in social behavior and ultrasonic vocalizations (USV) in juvenile heterozygous Cacna1c+/− (HET) rats. Specifically, HET females displayed increases in rough-and-tumble play that eliminated the typically observed sex difference between male and female rats. Interestingly, female wild-type Cacna1c+/+ (WT) pairs also showed a similar increase in social play when housed with HET females, suggesting their behavior may be influenced by HET cage mates. This indicates that the genetic makeup of the social environment related to Cacna1c can influence social play, yet systematic studies are lacking.MethodsIn the present study, we housed juvenile females in MIXED- or SAME-genotype cages and tested them in a social play paradigm with a same- and opposite-genotype partner.ResultsThe results show that the early social environment and the genotype of the play partner influence social play and 50-kHz USV emission. Experience with a WT play partner appears necessary for HET females to show comparable levels of play and 50-kHz USV emission. Same-genotype HET pairs played less and emitted fewer 50-kHz USV than same-genotype WT or opposite-genotype pairs; however, we found that the decrease in social play and 50-kHz USV in HET pairs can be rescued by playing with a WT partner. The effect was particularly prominent when the first play partner was WT, as we found it increased play and 50-kHz USV emission in all subsequent interactions with ensuing partners.ConclusionThese findings suggest that the genetic makeup related to the social environment and/or social peers influences social play in Cacna1c+/− haploinsufficient rats. Specifically, our results show that WT peers can rescue behavior and communication alterations in Cacna1c female rats. Our findings have important implications because they show that the genetic makeup of the social environment can divulge phenotypic changes in genetic rat models of neuropsychiatric disorders.
Triglyceride-glucose index predicts death in patients with stroke younger than 65
Authors: Liu Ruishan , Li Lijuan , Wang Lu , Zhang Shihong 
Published: August 2023

BackgroundThe triglyceride-glucose index (TGI), a reliable surrogate indicator of insulin resistance (IR), has been proven to be a predictor of the incidence of ischemic stroke. The role of TGI in predicting the outcomes of stroke patients remains controversial. Susceptibility to IR-related diseases varies among patients of different ages. The study aims to evaluate the predictive value of TGI levels on clinical outcomes of patients with ischemic stroke of different ages.MethodThis was a retrospective cohort study including patients with ischemic stroke in the Department of Neurology at West China Hospital. TGI was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. The patients were subdivided into 3 tertiles according to TGI levels. Multivariate logistic regression analyses were conducted to estimate the association between TGI levels and post-stroke outcomes among the whole patients, younger patients (&lt;65), and older patients (&gt;=65). The outcomes included death and unfavorable functional outcome (modified Rankin scale score 3–6) at 3 and 12 months after stroke.ResultsA total of 3,704 patients (men, 65.08%, mean age, 61.44 ± 14.15; women 34.92%, mean age, 65.70 ± 13.69) were enrolled in this study. TGI levels were not associated with 3 month or 12 month death in the whole patients. Patients with higher TGI levels (T2 and T3) had a higher risk of 3 month death than those had lower TGI levels (T1) in the younger group (T2 vs. T1: OR 2.64, 95% CI 1.03–6.79, p = 0.043; T3 vs. T1: OR 2.69, 95% CI 1.00–7.10, p = 0.049) but not in the older group. Additionally, Kaplan–Meier estimate analysis illustrated that the 12 month death risk was significantly higher in the group with the highest TGI among younger patients (p for log-rank test = 0.028) but not among older patients. There was an interactive effect between TGI and age on 3 month death (p for interaction = 0.013) and 12 month death (p for interaction = 0.027). However, TGI was not associated with unfavorable functional outcome at 3 month or 12 month after stroke.ConclusionElevated TGI independently predicts death at 3 months and 12 months in patients under 65 with ischemic stroke. Regulating TGI is expected to be an approach to enhance prognosis in young individuals affected by ischemic stroke.
C-NODDI: a constrained NODDI model for axonal density and orientation determinations in cerebral white matter
Authors: Alsameen Maryam H. , Gong Zhaoyuan , Qian Wenshu , Kiely Matthew , Triebswetter Curtis , Bergeron Christopher M. , Cortina Luis E. , Faulkner Mary E. , Laporte John P. , Bouhrara Mustapha 
Published: August 2023

PurposeNeurite orientation dispersion and density imaging (NODDI) provides measures of neurite density and dispersion through computation of the neurite density index (NDI) and the orientation dispersion index (ODI). However, NODDI overestimates the cerebrospinal fluid water fraction in white matter (WM) and provides physiologically unrealistic high NDI values. Furthermore, derived NDI values are echo-time (TE)-dependent. In this work, we propose a modification of NODDI, named constrained NODDI (C-NODDI), for NDI and ODI mapping in WM.MethodsUsing NODDI and C-NODDI, we investigated age-related alterations in WM in a cohort of 58 cognitively unimpaired adults. Further, NDI values derived using NODDI or C-NODDI were correlated with the neurofilament light chain (NfL) concentration levels, a plasma biomarker of axonal degeneration. Finally, we investigated the TE dependence of NODDI or C-NODDI derived NDI and ODI.ResultsODI derived values using both approaches were virtually identical, exhibiting constant trends with age. Further, our results indicated a quadratic relationship between NDI and age suggesting that axonal maturation continues until middle age followed by a decrease. This quadratic association was notably significant in several WM regions using C-NODDI, while limited to a few regions using NODDI. Further, C-NODDI-NDI values exhibited a stronger correlation with NfL concentration levels as compared to NODDI-NDI, with lower NDI values corresponding to higher levels of NfL. Finally, we confirmed the previous finding that NDI estimation using NODDI was dependent on TE, while NDI derived values using C-NODDI exhibited lower sensitivity to TE in WM.ConclusionC-NODDI provides a complementary method to NODDI for determination of NDI in white matter.
Similarities and differences between intermittent and continuous resting-state fMRI
Authors: Beresniewicz Justyna , Riemer Frank , Kazimierczak Katarzyna , Ersland Lars , Craven Alexander R. , Hugdahl Kenneth , Grüner Renate 
Published: August 2023

IntroductionFunctional Magnetic Resonance Imaging (fMRI) block-design experiments typically include active ON-blocks with presentation of cognitive tasks which are contrasted with OFF- blocks with no tasks presented. OFF-blocks in between ON-blocks can however, also be seen as a proxy for intermittent periods of resting, inducing temporary resting-states. We still do not know if brain activity during such intermittent periods reflects the same kind of resting-state activity as that obtained during a continuous period, as is typically the case in studies of the classic Default Mode Network (DMN). The purpose of the current study was therefore to investigate both similarities and differences in brain activity between intermittent and continuous resting conditions.MethodsThere were 47 healthy participants in the 3T fMRI experiment. Data for the intermittent resting-state condition were acquired from resting-periods in between active task-processing periods in a standard ON-OFF block design, with three different cognitive tasks presented during ON-blocks. Data for the continuous resting-state condition were acquired during a 5 min resting period after the task-design had been presented.Results and discussionThe results showed that activity was overall similar in the two conditions, but with some differences. These differences were within the DMN network, and for the interaction of DMN with other brain networks. DMN maps showed weak overlap between conditions in the medial prefrontal cortex (MPFC), and in particular for the intermittent compared to the continuous resting-state condition. Moreover, DMN showed strong connectivity with the salience network (SN) in the intermittent resting-state condition, particularly in the anterior insula and the supramarginal gyrus. The observed differences may reflect a “carry-over” effect from task-processing to the next resting-state period, not present in the continuous resting-state condition, causing interference from the ON-blocks. Further research is needed to fully understand the extent of differences between intermittent and continuous resting-state conditions.
Environmental carcinogens disproportionally mutate genes implicated in neurodevelopmental disorders
Authors: Baker Brennan H. , Zhang Shaoyi , Simon Jeremy M. , McLarnan Sarah M. , Chung Wendy K. , Pearson Brandon L. 
Published: August 2023

IntroductionDe novo mutations contribute to a large proportion of sporadic psychiatric and developmental disorders, yet the potential role of environmental carcinogens as drivers of causal de novo mutations in neurodevelopmental disorders is poorly studied.MethodsTo explore environmental mutation vulnerability of disease-associated gene sets, we analyzed publicly available whole genome sequencing datasets of mutations in human induced pluripotent stem cell clonal lines exposed to 12 classes of environmental carcinogens, and human lung cancers from individuals living in highly polluted regions. We compared observed rates of exposure-induced mutations in disease-related gene sets with the expected rates of mutations based on control genes randomly sampled from the genome using exact binomial tests. To explore the role of sequence characteristics in mutation vulnerability, we modeled the effects of sequence length, gene expression, and percent GC content on mutation rates of entire genes and gene coding sequences using multivariate Quasi-Poisson regressions.ResultsWe demonstrate that several mutagens, including radiation and polycyclic aromatic hydrocarbons, disproportionately mutate genes related to neurodevelopmental disorders including autism spectrum disorders, schizophrenia, and attention deficit hyperactivity disorder. Other disease genes including amyotrophic lateral sclerosis, Alzheimer’s disease, congenital heart disease, orofacial clefts, and coronary artery disease were generally not mutated more than expected. Longer sequence length was more strongly associated with elevated mutations in entire genes compared with mutations in coding sequences. Increased expression was associated with decreased coding sequence mutation rate, but not with the mutability of entire genes. Increased GC content was associated with increased coding sequence mutation rates but decreased mutation rates in entire genes.DiscussionOur findings support the possibility that neurodevelopmental disorder genetic etiology is partially driven by a contribution of environment-induced germ line and somatic mutations.