bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of high-plex data provides novel insights into the temporal artery processes of giant cell arteritis
Authors: Parreau Simon , Molina Elsa , Dumonteil Stéphanie , Goulabchand Radjiv , Naves Thomas , Bois Melanie C. , Akil Hussein , Terro Faraj , Fauchais Anne-Laure , Liozon Eric , Jauberteau Marie-Odile , Weyand Cornelia M. , Ly Kim-Heang 
Published: September 2023

ObjectiveTo identify the key coding genes underlying the biomarkers and pathways associated with giant cell arteritis (GCA), we performed an in situ spatial profiling of molecules involved in the temporal arteries of GCA patients and controls. Furthermore, we performed pharmacogenomic network analysis to identify potential treatment targets.MethodsUsing human formalin-fixed paraffin-embedded temporal artery biopsy samples (GCA, n = 9; controls, n = 7), we performed a whole transcriptome analysis using the NanoString GeoMx Digital Spatial Profiler. In total, 59 regions of interest were selected in the intima, media, adventitia, and perivascular adipose tissue (PVAT). Differentially expressed genes (DEGs) (fold-change &gt; 2 or &lt; −2, p-adjusted &lt; 0.01) were compared across each layer to build a spatial and pharmacogenomic network and to explore the pathophysiological mechanisms of GCA.ResultsMost of the transcriptome (12,076 genes) was upregulated in GCA arteries, compared to control arteries. Among the screened genes, 282, 227, 40, and 5 DEGs were identified in the intima, media, adventitia, and PVAT, respectively. Genes involved in the immune process and vascular remodeling were upregulated within GCA temporal arteries but differed across the arterial layers. The immune-related functions and vascular remodeling were limited to the intima and media.ConclusionThis study is the first to perform an in situ spatial profiling characterization of the molecules involved in GCA. The pharmacogenomic network analysis identified potential target genes for approved and novel immunotherapies.
A role of inflammaging in aortic aneurysm: new insights from bioinformatics analysis
Authors: Wang Shilin , Liu Hao , Yang Peiwen , Wang Zhiwen , Ye Ping , Xia Jiahong , Chen Shu 
Published: September 2023

IntroductionAortic aneurysms (AA) are prevalent worldwide with a notable absence of drug therapies. Thus, identifying potential drug targets is of utmost importance. AA often presents in the elderly, coupled with consistently raised serum inflammatory markers. Given that ageing and inflammation are pivotal processes linked to the evolution of AA, we have identified key genes involved in the inflammaging process of AA development through various bioinformatics methods, thereby providing potential molecular targets for further investigation.MethodsThe transcriptome data of AA was procured from the datasets GSE140947, GSE7084, and GSE47472, sourced from the NCBI GEO database, whilst gene data of ageing and inflammation were obtained from the GeneCards Database. To identify key genes, differentially expressed analysis using the “Limma” package and WGCNA were implemented. Protein-protein intersection (PPI) analysis and machine learning (ML) algorithms were employed for the screening of potential biomarkers, followed by an assessment of the diagnostic value. Following the acquisition of the hub inflammaging and AA-related differentially expressed genes (IADEGs), the TFs-mRNAs-miRNAs regulatory network was established. The CIBERSORT algorithm was utilized to investigate immune cell infiltration in AA. The correlation of hub IADEGs with infiltrating immunocytes was also evaluated. Lastly, wet laboratory experiments were carried out to confirm the expression of hub IADEGs.Results342 and 715 AA-related DEGs (ADEGs) recognized from GSE140947 and GSE7084 datasets were procured by intersecting the results of “Limma” and WGCNA analyses. After 83 IADEGs were obtained, PPI analysis and ML algorithms pinpointed 7 and 5 hub IADEGs candidates respectively, and 6 of them demonstrated a high diagnostic value. Immune cell infiltration outcomes unveiled immune dysregulation in AA. In the wet laboratory experiments, 3 hub IADEGs, including BLNK, HLA-DRA, and HLA-DQB1, finally exhibited an expression trend in line with the bioinformatics analysis result.DiscussionOur research identified three genes - BLNK, HLA-DRA, and HLA-DQB1- that play a significant role in promoting the development of AA through inflammaging, providing novel insights into the future understanding and therapeutic intervention of AA.
Impact of clozapine monotherapy on gut microbiota and metabolism in people with schizophrenia
Authors: Yin Feiyan , Shi Zhidao , Ma Xiquan , Ding Kai , Zhang Yuan , Ma Sha 
Published: September 2023

BackgroundClozapine is considered one of the most effective antipsychotic drugs, but it is most likely to cause metabolic abnormalities. Researchers have studied the causes of metabolic abnormalities caused by clozapine from multiple perspectives, but the reasons remain unclear.PurposeCharacterize the gut microbiota of people with schizophrenia taking clozapine, exploring the association between gut microbiota and glucose lipid metabolic markers in schizophrenia patients taking clozapine.Research designSixty-one long-term inpatients with schizophrenia in clozapine monotherapy were selected as study subjects. We got four subgroups by sex and the presence of metabolic syndrome.Data analysis16s analysis technology was applied at the genus level to determine the classification of gut microbiota. Then we compared the characteristics of gut microbiota and the association of gut microbiota with glucose lipid metabolic markers in each group.FindingsWe found differences in the diversity of gut microbiota among groups. The association between gut microbiota and glucose lipid metabolic markers was complicated. Gender was an important differentiating factor. Oscillibacter has a low abundance. However, it was the only genus associated with glycemic or lipids in each group. Among metabolic syndromes, Gemmiger was positively correlated with most lipids in females but negatively correlated in males, showing gender differences. In female non-metabolic syndromes, Bifidobacterium lost its probiotic character; instead, showing pathogenicity, which has strong positive correlations with fasting blood glucose and low-density lipoprotein but negative correlations with Apolipoprotein A1. Maybe schizophrenia, taking clozapine, and gender factors influenced the gut microbiota, which complicated our findings. The significance of the results remains to be determined by in-depth studies.
Switching to second line MS disease-modifying therapies is associated with decreased relapse rate
Authors: Marriott James John , Ekuma Okechukwu , Fransoo Randall , Marrie Ruth Ann 
Published: September 2023

Background and objectivesWhile randomized, controlled trials (RCTs) are the gold standard for determining treatment efficacy, they do not capture the effectiveness of treatment during real-world use. We aimed to evaluate the association between demographics and multiple sclerosis (MS) disease-modifying therapy (DMT) exposure, including treatment adherence and switches between different DMTs, on the risk of subsequent MS relapse.MethodsAll persons with relapsing-onset MS (pwRMS) living in Manitoba between 1999 and 2014 were identified from provincial healthcare databases using a validated case definition. Use of DMTs was abstracted from the provincial drug database covering all residents of Manitoba, including use of any DMT, stopping/starting any DMT, switches between different DMTs and adherence as defined by cumulative medication possession ratios (CUMMPRs) of 50, 70, 80 and 90%. Time to first-treated relapse was used as the outcome of interest in logistic regression and Cox-proportional hazards regression models adjusting for demographic covariates including age and year of diagnosis, sex, socioeconomic status and number of medical comorbidities.Results1780 pwRMS were identified, including 1,510 who were on DMT at some point in the study period. While total DMT exposure was not associated with the time to subsequent treated relapse, individuals who switched between more than 2 DMTs had higher post-switch rates of relapse. Switching to second-line DMTs was associated with a longer time to treated relapse in comparison to those who remained on a first-line DMT (HR 0.44; 95%CI: 0.32–0.62, p &lt; 0.0001).DiscussionSwitching to high-efficacy DMTs reduces the rates of subsequent MS relapse at the population level.
Pediatric traumatic brain injuries in war zones: a systematic literature review
Authors: Aguirre Alex S. , Rojas Kenny , Torres Alcy R. 
Published: September 2023

BackgroundPediatric casualties in war zones are a devastating consequence of armed conflicts, causing significant challenges for affected children, especially in the context of poor access to care. This study aimed to understand traumatic brain injuries (TBIs) in this high-risk population and to identify and provide information for the stakeholders, as well as to recognize severe long-term consequences and develop strategies to prevent them, thus minimizing their burden while aiding in the management of these cases.MethodsWe carried out a systematic literature review following PRISMA guidelines to identify publications discussing traumatic brain injuries in children in the context of war zones, and we analyzed all the collected data.ResultsOur study showed that head injuries were the most common casualty in war zones; male and female children were affected, and the mean age was 8–10 years. Most children were reported to be from Afghanistan, and blasts were the most common mechanism of injury. The mortality fluctuated from 3 to 47%.ConclusionThere is a lack of evidence-based information regarding the characterization, approach, and management of children with TBI in conflict zones. While the world finds ways to live in peace, there is an urgency to research, train, and deploy enough specialists to these areas, if governments are serious about improving outcomes for this population.
Cyclophosphamide augments the efficacy of in situ vaccination in a mouse melanoma model
Authors: Tsarovsky Noah , Felder Mildred , Heck Mackenzie , Slowinski Jacob , Rasmussen Kayla , VandenHeuvel Sabrina , Zaborek Jen , Morris Zachary S. , Erbe Amy K. , Sondel Paul M. , Rakhmilevich Alexander L. 
Published: September 2023

IntroductionWe have previously shown that an intratumoral (IT) injection of the hu14.18-IL2 immunocytokine (IC), an anti-GD2 antibody linked to interleukin 2, can serve as an in situ vaccine and synergize with local radiotherapy (RT) to induce T cell-mediated antitumor effects. We hypothesized that cyclophosphamide (CY), a chemotherapeutic agent capable of depleting T regulatory cells (Tregs), would augment in situ vaccination. GD2+ B78 mouse melanoma cells were injected intradermally in syngeneic C57BL/6 mice.MethodsTreatments with RT (12Gy) and/or CY (100 mg/kg i.p.) started when tumors reached 100-300 mm3 (day 0 of treatment), followed by five daily injections of IT-IC (25 mcg) on days 5-9. Tumor growth and survival were followed. In addition, tumors were analyzed by flow cytometry.ResultsSimilar to RT, CY enhanced the antitumor effect of IC. The strongest antitumor effect was achieved when CY, RT and IC were combined, as compared to combinations of IC+RT or IC+CY. Flow cytometric analyses showed that the combined treatment with CY, RT and IC decreased Tregs and increased the ratio of CD8+ cells/Tregs within the tumors. Moreover, in mice bearing two separate tumors, the combination of RT and IT-IC delivered to one tumor, together with systemic CY, led to a systemic antitumor effect detected as shrinkage of the tumor not treated directly with RT and IT-IC. Cured mice developed immunological memory as they were able to reject B78 tumor rechallenge.ConclusionTaken together, these preclinical results show that CY can augment the antitumor efficacy of IT- IC, given alone or in combination with local RT, suggesting potential benefit in clinical testing of these combinations.
Risk factors for lateral pelvic lymph node metastasis in patients with lower rectal cancer: a systematic review and meta-analysis
Authors: Zeng De-xing , Yang Zhou , Tan Ling , Ran Meng-ni , Liu Zi-lin , Xiao Jiang-wei 
Published: September 2023

Background and objectiveLateral pelvic lymph node (LPLN) metastasis is one of the prominent reasons for local recurrence (LR) in patients with rectal cancer (RC). The evaluation criteria of lateral lymph node dissection (LLND) for patients in eastern (mainly in Japan) and western countries have been controversial. The aim of this study was to analyse the risk factors for LPLN metastasis in order to guide surgical methods.MethodsWe searched relevant databases (Embase (Ovid), Medline (Ovid), PubMed, Cochrane Library, and Web of Science) for articles published between 1 January 2000 and 05 October 2022 to evaluate the risk factors for LPLN metastasis in patients with RC in this meta-analysis.ResultsA total of 24 articles with 5843 patients were included in this study. The overall results showed that female sex, age &lt;60 years, pretherapeutic CEA level &gt;5 ng/ml, clinical T4 stage (cT4), clinical M1 stage (cM1), distance of the tumour from the anal verge (AV) &lt;50 mm, tumour centre located below the peritoneal reflection (Rb), short axis (SA) of LPLN ≥8 mm before nCRT, short axis (SA) of LPLN ≥5 mm after nCRT, border irregularity of LPLN, tumour size ≥50 mm, pathological T3-4 stage (pT3-4), pathological N2 stage (pN2), mesorectal lymph node metastasis (MLNM), lymphatic invasion (LI), venous invasion (VI), CRM (+) and poor differentiation were significant risk factors for LPLN metastasis (P &lt;0.05).ConclusionThis study summarized almost all potential risk factors of LPLN metastasis and expected to provide effective treatment strategies for patients with LRC. According to the risk factors of lateral lymph node metastasis, we can adopt different comprehensive treatment strategies. High-risk patients can perform lateral lymph node dissection to effectively reduce local recurrence; In low-risk patients, we can avoid overtreatment, reduce complications and trauma caused by lateral lymph node dissection, and maximize patient survival and quality of life.
Self- and proxy-reported impaired social interaction in young adults with simple congenital heart defects
Authors: Lau-Jensen Sara Hirani , Asschenfeldt Benjamin , Evald Lars , Hjortdal Vibeke E. 
Published: September 2023

BackgroundSimple Congenital Heart Defects such as septal defects constitute a large proportion of Congenital Heart Defects. New research has demonstrated more co-morbidities than previously thought. In particular, co-morbidities involving neurocognitive, psychiatric, and social difficulties have been described. Neurocognitive and psychiatric morbidities affect social interaction. Social interaction is important in everyday social life (education, work life, family life). In this study, we investigated social interaction through self- and proxy-answered Social Responsiveness Scale 2 (SRS-2) in young adults with simple Congenital Heart Defects and compared their social interaction profile to healthy matched controls.MethodsWe included a total of 80 patients with either atrial or ventricular septal defect (age 26.6 years) and 38 heart-healthy, age, sex, and ISCED educational matched controls (age: 25.3 years). A close relative proxy from each participant took part in the study as well. All participants answered the Social Responsiveness Scale 2 (SRS-2) (n = 225). Our primary and secondary outcomes were the SRS-2 Total score and the SRS-2 sub-scores.ResultsIn the Congenital Heart Defects group, 31.3% had a Total score above 60 compared to 7.9% in the control group (p = 0.005, RR = 3.96). The participants with a septal defect had a higher Total score (52.5 vs. 45.5, p = 0.004), a higher Social Cognition sub-score (55.0 vs. 47.0, p = 0.0004), and a higher Social Motivation sub-score (50.0 vs. 45.0, p = 0.003) than the heart-healthy participants. We found no difference between the two groups regarding the sub-scores of Social Awareness and Social Communication. A multiple linear regression model showed that the variable that explained most of the variation in Total Score was having a previously diagnosed psychiatric disorder.ConclusionWe found that young adults with atrial or ventricular septal defects have a fourfold increased risk of social interaction difficulties compared to heart-healthy peers. They have a social interaction profile, with difficulties in social cognition and social motivation, and preserved social awareness and social communication. Psychiatric morbidity explained most of the variation in social interaction problems. As social difficulties and psychiatric morbidities are intertwined, social interaction difficulties could be an indication of already underlying psychiatric morbidities or a risk factor for future psychiatric morbidity.
CCR9 overexpression promotes T-ALL progression by enhancing cholesterol biosynthesis
Authors: Jamal Muhammad , Lei Yufei , He Hengjing , Zeng Xingruo , Bangash Hina Iqbal , Xiao Di , Shao Liang , Zhou Fuling , Zhang Quiping 
Published: September 2023

Introduction: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy of the lymphoid progenitor cells, contributing to ∼ 20% of the total ALL cases, with a higher prevalence in adults than children. Despite the important role of human T-ALL cell lines in understanding the pathobiology of the disease, a detailed comparison of the tumorigenic potentials of two commonly used T-ALL cell lines, MOLT4 and JURKAT cells, is still lacking.Methodology: In the present study, NOD-PrkdcscidIL2rgdull (NTG) mice were intravenously injected with MOLT4, JURKAT cells, and PBS as a control. The leukemiac cell homing/infiltration into the bone marrow, blood, liver and spleen was investigated for bioluminescence imaging, flow cytometry, and immunohistochemistry staining. Gene expression profiling of the two cell lines was performed via RNA-seq to identify the differentially expressed genes (DEGs). CCR9 identified as a DEG, was further screened for its role in invasion and metastasis in both cell lines in vitro. Moreover, a JURKAT cell line with overexpressed CCR9 (Jurkat-OeCCR9) was investigated for T-ALL formation in the NTG mice as compared to the GFP control. Jurkat-OeCCR9 cells were then subjected to transcriptome analysis to identify the genes and pathways associated with the upregulation of CCR9 leading to enhanced tumirogenesis. The DEGs of the CCR9-associated upregulation were validated both at mRNA and protein levels. Simvastatin was used to assess the effect of cholesterol biosynthesis inhibition on the aggressiveness of T-ALL cells.Results: Comparison of the leukemogenic potentials of the two T-ALL cell lines showed the relatively higher leukemogenic potential of MOLT4 cells, characterized by their enhanced tissue infiltration in NOD-PrkdcscidIL2rgdull (NTG) mice. Transcriptmoe analysis of the two cell lines revealed numerous DEGs, including CCR9, enriched in vital signaling pathways associated with growth and proliferation. Notably, the upregulation of CCR9 also promoted the tissue infiltration of JURKAT cells in vitro and in NTG mice. Transcriptome analysis revealed that CCR9 overexpression facilitated cholesterol production by upregulating the expression of the transcriptional factor SREBF2, and the downstream genes: MSMO1, MVD, HMGCS1, and HMGCR, which was then corroborated at the protein levels. Notably, simvastatin treatment reduced the migration of the CCR9-overexpressing JURKAT cells, suggesting the importance of cholesterol in T-ALL progression.Conclusions: This study highlights the distinct tumorigenic potentials of two T-ALL cell lines and reveals CCR9-regulated enhanced cholesterol biosynthesis in T-ALL.
Dispositional mindfulness profiles in pregnant women: relationships with dyadic adjustment and symptoms of depression and anxiety
Authors: Echabe-Ecenarro Oiana , Orue Izaskun , Calvete Esther 
Published: September 2023

IntroductionPregnancy is a time of major transition that can be stressful for women. Dispositional mindfulness may protect individuals when they face stress. Recent studies have adopted a person-centered approach to examine the role of mindfulness by identifying subtypes of individuals based on their scores in five mindfulness facets. Latent profile analysis was used to identify different mindfulness profiles in a sample of pregnant women, and we explored the relationships between these profiles, depression and anxiety symptoms, and whether dyadic adjustment mediated these relationships.MethodA total of 535 women aged 18–45 years in their 26th week of pregnancy completed questionnaires regarding mindfulness, dyadic satisfaction and cohesion, and depression and anxiety symptoms.ResultsThree profiles were identified: (1) low mindfulness (53.8%), (2) moderate mindfulness (34.3%), and (3) non-judgmentally aware (11.9%). The most adaptive profile was the non-judgmentally aware profile. Compared to the low mindfulness profile, the non-judgmentally aware profile and the moderate mindfulness profile were related to fewer symptoms of depression and anxiety, and these relationships were partly mediated by dyadic satisfaction.DiscussionThese results suggest that analyzing each pregnant woman’s mindfulness profile can improve the prevention of and interventions for anxiety and depression.
Testing a mediation model of teacher caring, grit, and student wellbeing in English as a foreign language students
Authors: Zhou Guanbing 
Published: September 2023

IntroductionThis study delves into the influence of perceived teacher caring on the wellbeing of Chinese English as a Foreign Language (EFL) students, with a specific focus on the potential mediating effect of grit. With a sample size of 748 EFL students hailing from diverse Chinese universities, we aimed to shed light on the connections between perceived teacher caring, student wellbeing, and the mediating factor of grit.MethodsTo address our research questions, we collected data through self-report questionnaires that gauged perceived teacher caring, student wellbeing, and levels of grit. By utilizing structural equation modeling, we were able to rigorously assess both the direct and indirect impacts of teacher caring on student wellbeing.ResultsOur analysis uncovered a noteworthy and positive correlation between perceived teacher caring and student wellbeing. Furthermore, our findings indicated that grit plays a significant mediating role in this relationship. This suggests that students who exhibit higher levels of grit are more inclined to experience heightened levels of wellbeing.DiscussionThe outcomes of this study underscore the significance of nurturing positive teacher-student relationships within the EFL context. The identification of grit as a mediator emphasizes its role in fostering enhanced student wellbeing. These findings collectively emphasize the intertwined nature of teacher caring, grit, and student wellbeing. Educators should consider these insights for their teaching practices, while researchers can use this study as a foundation for further investigations in this domain.