bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide detection of m6A-associated SNPs in atrial fibrillation pathogenesis
Authors: Huang Yan , Tan Yuqian , Yao Yuan , Gu Linglong , Huang Liusong , Song Tao 
Published: May 2023

ObjectiveN6-Methyladenosine (m6A) modification is of great importance in both the pathological conditions and physiological process. The m6A single nucleotide polymorphisms (SNPs) are associated with cardiovascular diseases including coronary artery disease, heart failure. However, it is unclear whether m6A-SNPs are involved in atrial fibrillation (AF). Here, we aimed to explore the relationship between m6A-SNPs and AF.MethodThe relationship between m6A-SNPs and AF was evaluated by analyzing the AF genome-wide association study (GWAS) and m6A-SNPs annotated by the m6AVar database. Further, eQTL and gene differential expression analysis were performed to confirm the association between these identified m6A-SNPs and their target genes in the development of AF. Moreover, we did the GO enrichment analysis to figure out the potential functions of these m6A-SNPs affected genes.ResultTotally, 105 m6A-SNPs were identified to be significantly associated with AF (FDR &lt; 0.05), among which 7 showed significant eQTL signals on local genes in the atrial appendage. By using four public AF gene expression datasets, we identified genes SYNE2, USP36, and THAP9 containing SNPs rs35648226, rs900349, and rs1047564 were differentially expressed in AF population. Further, SNPs rs35648226 and rs1047564 are potentially associated with AF by affecting m6A modification and both of them might have an interaction with RNA-binding protein, PABPC1.ConclusionIn summary, we identified m6A-SNPs associated with AF. Our study provided new insights into AF development as well as AF therapeutic target.
Advanced glycation end products and their soluble receptor (sRAGE) in patients with Hashimoto’s thyroiditis on levothyroxine substitution
Authors: Csiha Sára , Molnár István , Halmi Sándor , Hutkai Dávid , Lőrincz Hajnalka , Somodi Sándor , Katkó Mónika , Harangi Mariann , Paragh György , Nagy Endre V. , Berta Eszter , Bodor Miklós 
Published: May 2023

BackgroundAdvanced glycation end products (AGEs) are heterogenous group of irreversible chemical moieties originated from non-enzymatic glycation and oxidation of proteins, nucleic acids, and lipids. The engagement of AGEs with their chief cellular receptor (RAGE) activates a myriad of signaling pathways contributing to the progression of chronic diseases like autoimmune thyroiditis, type 2 diabetes mellitus and its complications. Soluble RAGE (sRAGE) prevents AGE-RAGE interaction in a competitive manner.ObjectiveWe investigated the association between serum AGE, sRAGE and thyroid function in 73 Hashimoto thyroiditis patients (HT) on levothyroxine substitution, and in 83 age, BMI and gender-matched healthy controls.MethodsThe serum AGEs levels were determined by autofluorescence on a multi-mode microplate reader, and the serum sRAGE levels by ELISA method.ResultsMean AGE level was lower (10.71 vs 11.45 AU/µg protein; p=0.046), while mean sRAGE level was higher (923 vs 755 pg/mL; p&lt;0.0005) in the serum of HT patients than the controls. AGE correlated with age, while sRAGE correlated negatively with BMI in both groups. We found negative correlation between AGE and fT3 levels (r=-0.32; p=0.006) and sRAGE and TSH levels (r=-0.27; p=0.022) in HT patients, while we failed to find association between AGE, sRAGE and parameters of thyroid function in the control group. Median AGE/sRAGE ratio was lower in HT patients than in controls (2.4, IQR 1.9 – 3.1 vs 3.3, IQR 2.3 – 4.1 AU/pg; p &lt; 0.001). In HT patients, the AGE/sRAGE ratio correlated positively with BMI and correlated negatively with fT3.ConclusionAccording to our results in HT patients lower TSH and higher fT3 levels within the reference range is accompanied by a favorable AGE/RAGE balance. Further investigations are needed to confirm these results.
Resting heart rate (variability) and cognition relationships reveal cognitively healthy individuals with pathological amyloid/tau ratio
Authors: Molloy Cathleen , Choy Elizabeth H. , Arechavala Rebecca J. , Buennagel David , Nolty Anne , Spezzaferri Mitchell R. , Sin Caleb , Rising Shant , Yu Jeremy , Al-Ezzi Abdulhakim , Kleinman Michael T. , Kloner Robert A. , Arakaki Xianghong 
Published: May 2023

IntroductionResting heart rate (HR) and heart rate variability (HRV) have been linked with cognition in the general population and in older individuals. The knowledge of this aspect of heart-brain relationship is relatively absent in older individuals with early Alzheimer's disease (AD) pathology. This study explores relationships of the HR, HRV, and cognition in cognitively healthy individuals with pathological amyloid/tau ratio (CH-PATs) in cerebral spinal fluid (CSF) compared to those with normal ratio (CH-NATs).MethodsWe examined the relationships between 1) resting HR and Mini‐Mental State Examination (MMSE); 2) resting HR and brain processing during Stroop interference; and 3) resting vagally mediated HRV (vmHRV) and task switching performance.ResultsOur studies showed that compared to CH-NATs, those CH-PATs with higher resting HR presented with lower MMSE, and less brain activation during interference processing. In addition, resting vmHRV was significantly correlated with task switching accuracy in CH-NATs, but not in CH-PATs.DiscussionThese three different tests indicate dysfunctional heart-brain connections in CH-PATs, suggesting a potential cardio-cerebral dysfunctional integration.
Staphylococcus epidermidis isolates from atopic or healthy skin have opposite effect on skin cells: potential implication of the AHR pathway modulation
Authors: Landemaine Leslie , Da Costa Gregory , Fissier Elsa , Francis Carine , Morand Stanislas , Verbeke Jonathan , Michel Marie-Laure , Briandet Romain , Sokol Harry , Gueniche Audrey , Bernard Dominique , Chatel Jean-Marc , Aguilar Luc , Langella Philippe , Clavaud Cecile , Richard Mathias L. 
Published: May 2023

IntroductionStaphylococcus epidermidis is a commensal bacterium ubiquitously present on human skin. This species is considered as a key member of the healthy skin microbiota, involved in the defense against pathogens, modulating the immune system, and involved in wound repair. Simultaneously, S. epidermidis is the second cause of nosocomial infections and an overgrowth of S. epidermidis has been described in skin disorders such as atopic dermatitis. Diverse isolates of S. epidermidis co-exist on the skin. Elucidating the genetic and phenotypic specificities of these species in skin health and disease is key to better understand their role in various skin conditions. Additionally, the exact mechanisms by which commensals interact with host cells is partially understood. We hypothesized that S. epidermidis isolates identified from different skin origins could play distinct roles on skin differentiation and that these effects could be mediated by the aryl hydrocarbon receptor (AhR) pathway.MethodsFor this purpose, a library of 12 strains originated from healthy skin (non-hyperseborrheic (NH) and hyperseborrheic (H) skin types) and disease skin (atopic (AD) skin type) was characterized at the genomic and phenotypic levels.Results and discussionHere we showed that strains from atopic lesional skin alter the epidermis structure of a 3D reconstructed skin model whereas strains from NH healthy skin do not. All strains from NH healthy skin induced AhR/OVOL1 path and produced high quantities of indole metabolites in co-culture with NHEK; especially indole-3-aldehyde (IAld) and indole-3-lactic acid (ILA); while AD strains did not induce AhR/OVOL1 path but its inhibitor STAT6 and produced the lowest levels of indoles as compared to the other strains. As a consequence, strains from AD skin altered the differentiation markers FLG and DSG1. The results presented here, on a library of 12 strains, showed that S. epidermidis originated from NH healthy skin and atopic skin have opposite effects on the epidermal cohesion and structure and that these differences could be linked to their capacity to produce metabolites, which in turn could activate AHR pathway. Our results on a specific library of strains provide new insights into how S. epidermidis may interact with the skin to promote health or disease.
Helicobacter pylori infection may influence prevalence and disease course in myelin oligodendrocyte glycoprotein antibody associated disorder (MOGAD) similar to MS but not AQP4-IgG associated NMOSD
Authors: Malli Chaithra , Pandit Lekha , D’Cunha Anita , Sudhir Akshatha 
Published: May 2023

BackgroundHelicobacter pylori (Hp) persists after colonizing the gut in childhood, and potentially regulates host immune system through this process. Earlier studies have shown that Hp infection in childhood, may protect against MS in later life. Such an association was not seen with AQP4-IgG positive NMOSD, while the association with MOGAD is unclear.ObjectiveTo evaluate frequency of Hp IgG among patients with MOGAD, MS, NMOSD and matched controls and its effect on disease course. To ascertain whether childhood socio economic factors were linked to prevalence of Hp infection.MethodsIn all, 99 patients diagnosed to have MOGAD, 99 AQP4 IgG+ NMOSD, 254MS and 243 matched controls were included. Patient demographics, diagnosis, age at disease onset, duration and the last recorded expanded disability status scale (EDSS) were obtained from our records. Socioeconomic and educational status was queried using a previously validated questionnaire. Serum HpIgG was detected using ELISA kits (Vircell, Spain).ResultFrequency of Hp IgG was significantly lower among MOGAD (28.3% vs 44%, p-0.007) and MS (21.2% vs 44%, p-0.0001) but not AQP4-IgG+ NMOSD patients (42.4% vs 44%, p-0.78) when compared to controls. Frequency of Hp IgG in MOGAD &amp; MS patients combined (MOGAD-MS) was significantly lower than those with NMOSD (23.2% vs 42.4%, p- 0.0001). Seropositive patients with MOGAD- MS were older (p-0.001. OR -1.04, 95% CI- 1.01- 1.06) and had longer disease duration (p- 0.04, OR- 1.04, 95% CI- 1.002- 1.08) at time of testing. Educational status was lower among parents/caregivers of this study cohort (p- 0.001, OR -2.34, 95% CI- 1.48-3.69) who were Hp IgG+.ConclusionsIn developing countries Hp infection may be a significant environmental factor related to autoimmune demyelinating CNS disease. Our preliminary data suggests that Hp may exert a differential influence - a largely protective role for MS-MOGAD but not NMOSD and may influence disease onset and course. This differential response maybe related to immuno-pathological similarities between MOGAD and MS in contrast to NMOSD. Our study further underscores the role of Hp as a surrogate marker for poor gut hygiene in childhood and its association with later onset of autoimmune diseases.
Additive manufacturing of metal-polymer hybrid parts: the influence of as-printed LPBF surface roughness on the joint strength
Authors: Belei C. , Effertz P. S. , Meier B. , Amancio-Filho S. T. 
Published: May 2023

As-printed Laser-Powder Bed Fusion (LPBF) surfaces can provide anchoring spots for the infiltration of polymer printed by Fused Filament Fabrication (FFF), enhancing metal-polymer joint strength. This work evaluates the influence of the as-printed LPBF surface roughness and FFF parameters on the strength of Ti-6Al-4V/PA-CF joints produced by this process combination. A three-point bending testing method based on ISO 14679:1997 was deployed, whereby the energy dissipated by the joint interface was measured. Roughness was varied by 3D-printing the substrate with different inclination angles; Height and printing speed of the coating layer (the polymer layer in direct contact with the metal) were also varied. Data was interpreted using a combination between Decision Tree and Gradient Boosting Regression, ultimately suggesting that printing speed is the prominent parameter followed by inclination angle for joint strength. Additionally, the combined effect of low printing speed and inclination angle resulted in the highest energy absorption at the interface (&gt;200 J).
Differences in the neural basis and transcriptomic patterns in acute and persistent pain-related anxiety-like behaviors
Authors: Fang Shunchang , Qin Yuxin , Yang Shana , Zhang Hongyang , Zheng Jieyan , Wen Songhai , Li Weimin , Liang Zirui , Zhang Xiaomin , Li Boxing , Huang Lianyan 
Published: May 2023

BackgroundBoth acute and persistent pain is associated with anxiety in clinical observations, but whether the underlying neural mechanisms differ is poorly understood.MethodsWe used formalin or complete Freund’s adjuvant (CFA) to induce acute or persistent pain. Behavioral performance was assessed by the paw withdrawal threshold (PWT), open field (OF), and elevated plus maze (EPM) tests. C-Fos staining was used to identify the activated brain regions. Chemogenetic inhibition was further performed to examine the necessity of brain regions in behaviors. RNA sequencing (RNA-seq) was used to identify the transcriptomic changes.ResultsBoth acute and persistent pain could lead to anxiety-like behavior in mice. The c-Fos expression indicates that the bed nucleus of the stria terminalis (BNST) is activated only in acute pain, whereas the medial prefrontal cortex (mPFC) is activated only in persistent pain. Chemogenetic manipulation reveals that the activation of the BNST excitatory neurons is required for acute pain-induced anxiety-like behaviors. In contrast, the activation of the prelimbic mPFC excitatory neurons is essential for persistent pain-induced anxiety-like behaviors. RNA-seq reveals that acute and persistent pain induces differential gene expression changes and protein–protein interaction networks in the BNST and prelimbic mPFC. The genes relevant to neuronal functions might underline the differential activation of the BNST and prelimbic mPFC in different pain models, and be involved in acute and persistent pain-related anxiety-like behaviors.ConclusionDistinct brain regions and gene expression patterns are involved in acute and persistent pain-related anxiety-like behaviors.
RedTell: an AI tool for interpretable analysis of red blood cell morphology
Authors: Sadafi Ario , Bordukova Maria , Makhro Asya , Navab Nassir , Bogdanova Anna , Marr Carsten 
Published: May 2023

Introduction: Hematologists analyze microscopic images of red blood cells to study their morphology and functionality, detect disorders and search for drugs. However, accurate analysis of a large number of red blood cells needs automated computational approaches that rely on annotated datasets, expensive computational resources, and computer science expertise. We introduce RedTell, an AI tool for the interpretable analysis of red blood cell morphology comprising four single-cell modules: segmentation, feature extraction, assistance in data annotation, and classification.Methods: Cell segmentation is performed by a trained Mask R-CNN working robustly on a wide range of datasets requiring no or minimum fine-tuning. Over 130 features that are regularly used in research are extracted for every detected red blood cell. If required, users can train task-specific, highly accurate decision tree-based classifiers to categorize cells, requiring a minimal number of annotations and providing interpretable feature importance.Results: We demonstrate RedTell’s applicability and power in three case studies. In the first case study we analyze the difference of the extracted features between the cells coming from patients suffering from different diseases, in the second study we use RedTell to analyze the control samples and use the extracted features to classify cells into echinocytes, discocytes and stomatocytes and finally in the last use case we distinguish sickle cells in sickle cell disease patients.Discussion: We believe that RedTell can accelerate and standardize red blood cell research and help gain new insights into mechanisms, diagnosis, and treatment of red blood cell associated disorders.
Study protocol: the pragmatic, exploratory DELTA-JU trial of the group-based multimodal DELTA intervention for abstinent adolescents with substance use disorders living in youth welfare institutions
Authors: Kuitunen-Paul Sören , Basedow Lukas A. , Roessner Veit , Golub Yulia 
Published: May 2023

BackgroundThe DELTA intervention contains 16 weekly group sessions plus additional individual sessions and educational session for parents. It aims to reduce substance use and related problems such as substance use disorders (SUD) in adolescents. Recent results indicated positive effects in psychiatric outpatients. Conducting DELTA in youth welfare settings seems feasible, however, organizational and content adjustments such as smoking cessation elements should be added in order to reduce relapse risks and to prevent negative health consequences.Methods/designThe pre-registered DELTA-JU study (German Clinical Trials Register, DRKS00027913) is separated into three stages: In the adjustment stage during months 1–4, we will revise the DELTA manual based on semi-structured interviews (n = 10) with personnel from youth welfare institutions specialized in serving adolescents with SUD in the study region, analyzed with content analysis. In the sampling stage during months 5–22, participants qualifying for a SUD and willing to regularly participate in the 16 weekly DELTA-JU group sessions will be enrolled to either one of two arms (cluster randomization: immediate intervention, waitlist with subsequent intervention 16 weeks later). Adolescents will be assessed at baseline and follow-up (16 weeks after first group session) with an additional pre-assessment (16 weeks before intervention starts) for the waitlist group. Assessment procedures include questionnaires and clinical interviews among others. At the same time, institutional personnel will receive a 1-day workshop on SUD-relevant topics based on the DELTA parental education group and on feedback from the qualitative interviews. Personnel will also be assessed twice with questionnaires. In the dissemination stage during months 23–24, final study evaluation results will be prepared and submitted for publication.DiscussionThis study will create a setting-specific manual for vulnerable adolescents suffering from SUDs, and, in many cases, from co-occurring mental disorders. If shown to be effective, DELTA-JU can be disseminated within other institutions of youth welfare.
The effects of childhood maltreatment on adolescent non-suicidal self-injury behavior: mediating role of impulsivity
Authors: Li Xi , Liu Xiao-Li , Wang Yu-Jing , Zhou Dong-Sheng , Yuan Ti-Fei 
Published: May 2023

BackgroundNon-suicidal self-injury (NSSI) severely challenges mental health in adolescents. Childhood maltreatment experience acts as high-risk factor for adolescents to engage in NSSI behaviors. On the other hand, impulsivity or loss of control sets the threshold for NSSI execution. Here we examined the effects of childhood maltreatment on adolescent NSSI-related clinical outcomes and the potential role of impulsivity.MethodsWe assessed the clinical data of 160 hospitalized NSSI adolescents and recruited 64 age-matched healthy subjects as a control group. The clinical symptoms of NSSI are expressed by the NSSI frequency, depression, and anxiety measured by the Ottawa Self-Injury Inventory, the Beck Depression Inventory, and the Beck Anxiety Inventory. Childhood maltreatment and impulsivity were assessed with Childhood Trauma Questionnaire and Barratt Impulsiveness Scale.ResultsThe results showed that when compared to HC group, NSSI group is more likely to experience childhood maltreatment. Notably, NSSI group with Childhood maltreatment accompanies higher trait impulsivity and exacerbated clinical outcomes, such as NSSI frequency, depression and anxiety symptoms. Mediation analyses indicated that the association between childhood maltreatment and NSSI-related clinical outcomes was partially explained by impulsivity.ConclusionWe found that NSSI adolescents have a higher proportion of childhood maltreatment. Impulsivity plays a mediating role between childhood maltreatment and NSSI behaviors.
Assessing goal-directed behavior in virtual reality with the neuropsychological task EPELI: children prefer head-mounted display but flat screen provides a viable performance measure for remote testing
Authors: Seesjärvi Erik , Laine Matti , Kasteenpohja Kaisla , Salmi Juha 
Published: May 2023

Background and objective: EPELI (Executive Performance of Everyday LIving) is a Virtual Reality (VR) task that was developed to study goal-directed behavior in everyday life contexts in children. In this study, we had 72 typically developing 9- to 13-year-old children to play EPELI with an immersive version implemented with a head-mounted display (HMD) and a non-immersive version employing a flat screen display (FSD) in a counterbalanced order to see if the two versions yield similar results. The children’s everyday executive functions were assessed with the parent-rated Behavior Rating Inventory for Executive Functions (BRIEF) questionnaire. To assess the applicability of EPELI for online testing, half of the flat screen display version gameplays were conducted remotely and the rest in the laboratory.Results: All EPELI performance measures were correlated across the versions. The children’s performance was mostly similar in the two versions, but small effects reflecting higher performance in FSD-EPELI were found in the measures of Total score, Task efficacy, and Time-based prospective memory score. The children engaged in more active time monitoring in FSD-EPELI. While the children evaluated the feeling of presence and usability of both versions favorably, most children preferred HMD-EPELI, and evaluated its environment to be more involving and realistic. Both versions showed only negligible problems with the interface quality. No differences in task performance or subjective evaluations were found between the home-based and laboratory-based assessments of FSD-EPELI. In both EPELI versions, the efficacy measures were correlated with BRIEF on the first assessment, but not on the second. This raises questions about the stability of the associations reported between executive function tasks and questionnaires.Conclusions: Both the HMD and FSD versions of EPELI are viable tools for the naturalistic assessment of goal-directed behavior in children. While the HMD version provides a more immersive user experience and naturalistic movement tracking, the FSD version can maximize scalability, reachability, and cost efficacy, as it can be used with common hardware and remotely. Taken together, the findings highlight similarities between the HMD and FSD versions of a cognitively complex VR task, but also underline the specific advantages of these common presentation modes.