bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ferroptosis-related biomarkers for Alzheimer’s disease: Identification by bioinformatic analysis in hippocampus
Authors: Wang Binyang , Fu Chenyang , Wei Yuanyuan , Xu Bonan , Yang Rongxing , Li Chuanxiong , Qiu Meihua , Yin Yong , Qin Dongdong 
Published: November 2022

BackgroundGlobally, Alzheimer’s Disease (AD) accounts for the majority of dementia, making it a public health concern. AD treatment is limited due to the limited understanding of its pathogenesis. Recently, more and more evidence shows that ferroptosis lead to cell death in the brain, especially in the regions of the brain related to dementia.Materials and methodsThree microarray datasets (GSE5281, GSE9770, GSE28146) related to AD were downloaded from Gene Expression Omnibus (GEO) datasets. Ferroptosis-related genes were extracted from FerrDb database. Data sets were separated into two groups. GSE5281 and GSE9770 were used to identify ferroptosis-related genes, and GSE28146 was used to verify results. During these processes, protein–protein interaction (PPI), the Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. Finally, the differentiated values of ferroptosis-related genes were determined by receiver operator characteristic (ROC) monofactor analysis to judge their potential quality as biomarkers.ResultsTwenty-four ferroptosis-related genes were obtained. Using STRING (https://cn.string-db.org/) and Cytoscape with CytoHubba, the top 10 genes (RB1, AGPAT3, SESN2, KLHL24, ALOX15B, CA9, GDF15, DPP4, PRDX1, UBC, FTH1, ASNS, GOT1, PGD, ATG16L1, SLC3A2, DDIT3, RPL8, VDAC2, GLS2, MTOR, HSF1, AKR1C3, NCF2) were identified as target genes. GO analysis revealed that response to carboxylic acid catabolic process, organic acid catabolic process, alpha-amino acid biosynthetic process and cellular amino acid biosynthetic process were the most highly enriched terms. KEGG analysis showed that these overlapped genes were enriched in p53 signaling pathways, longevity regulating pathway, mTOR signaling pathway, type 2 diabetes mellitus and ferroptosis. Box plots and violine plots were created and verified to confirm the significance of identified target genes. Moreover, ROC monofactor analysis was performed to determine the diagnostic value of identified genes. Two genes (ASNS, SESN2) were subsequently obtained. For the tow genes, STRING was used to obtain the five related genes and determined enriched GO terms and KEGG pathways for those genes.ConclusionOur results suggest that ASNS and SENS2 may serve as potential diagnostic biomarkers for AD and provide additional evidence regarding the essential role of ferroptosis in AD.
Ultrastructural destruction of neurovascular unit in experimental cervical spondylotic myelopathy
Authors: Li Guang-Sheng , Wang Xu-Xiang , Tan Ron-Bang , Wang Kang-Heng , Hu Xiao-song , Hu Yong 
Published: November 2022

Background and purposeThe pathogenesis of cervical spondylotic myelopathy (CSM) remains unclear. This study aimed to explore the ultrastructural pathology of neurovascular unit (NVU) during natural development of CSM.MethodsA total of 24 rats were randomly allocated to the control group and the CSM group. Basso–Beattie–Bresnahan (BBB) scoring and somatosensory evoked potentials (SEP) were used as functional assessments. Hematoxylin–eosin (HE), toluidine blue (TB), and Luxol fast blue (LFB) stains were used for general structure observation. Transmission electron microscopy (TEM) was applied for investigating ultrastructural characteristics.ResultsThe evident compression caused significant neurological dysfunction, which was confirmed by the decrease in BBB score and SEP amplitude, as well as the prolongation of SEP latency (P &lt; 0.05). The histopathological findings verified a significant decrease in the amount of Nissl body and myelin area and an increase in vacuolation compared with the control group (P &lt; 0.05). The TEM results revealed ultrastructural destruction of NVU in several forms, including: neuronal degeneration and apoptosis; disruption of axonal cytoskeleton (neurofilaments) and myelin sheath and dystrophy of axonal terminal with dysfunction mitochondria; degenerative oligodendrocyte, astrocyte, and microglial cell inclusions with degenerating axon and dystrophic dendrite; swollen microvascular endothelium and loss of tight junction integrity; corroded basement membrane and collapsed microvascular wall; and proliferated pericyte and perivascular astrocytic endfeet. In the CSM group, reduction was observed in the amount of mitochondria with normal appearance and the number of cristae per mitochondria (P &lt; 0.05), while no substantial drop of synaptic vesicle number was seen (P &gt; 0.05). Significant narrowing of microvascular lumen size was also observed, accompanied by growth in the vascular wall area, endothelial area, basement membrane thickness, astrocytic endfeet area, and pericyte coverage area (rate) (P &lt; 0.05).ConclusionAltogether, the findings of this study demonstrated ultrastructural destruction of NVU in an experimental CSM model with dorsal–lateral compression, revealing one of the crucial pathophysiological mechanisms of CSM.
Neuroprotection of cannabidiol in epileptic rats: Gut microbiome and metabolome sequencing
Authors: Gong Xiaoxiang , Liu Lingjuan , Li Xingfang , Xiong Jie , Xu Jie , Mao Dingan , Liu Liqun 
Published: November 2022

AimsEpilepsy is a neurological disease occurring worldwide. Alterations in the gut microbial composition may be involved in the development of Epilepsy. The study aimed to investigate the effects of cannabidiol (CBD) on gut microbiota and the metabolic profile of epileptic rats.Materials and methods and resultsA temporal lobe epilepsy rat model was established using Li-pilocarpine. CBD increased the incubation period and reduced the epileptic state in rats. Compared to epileptic rats, the M1/M2 ratio of microglia in the CBD group was significantly decreased. The expression of IL-1β, IL-6, and TNF-α in the CBD group decreased, while IL-10, IL-4, and TGF-β1 increased. 16S rDNA sequencing revealed that the ANOSIM index differed significantly between the groups. At the genus level, Helicobacter, Prevotellaceae_UCG-001, and Ruminococcaceae_UCG-005 were significantly reduced in the model group. CBD intervention attenuated the intervention effects of Li-pilocarpine. Roseburia, Eubacterium_xylanophilum_group, and Ruminococcus_2 were strongly positively correlated with proinflammatory cytokine levels. CBD reversed dysregulated metabolites, including glycerophosphocholine and 4-ethylbenzoic acid.ConclusionCBD could alleviate the dysbiosis of gut microbiota and metabolic disorders of epileptic rats. CBD attenuated Epilepsy in rats might be related to gut microbial abundance and metabolite levels.Significance and impact of studyThe study may provide a reliable scientific clue to explore the regulatory pathway of CBD in alleviating Epilepsy.
Case report: Undifferentiated sarcoma with multiple tumors involved in Lynch syndrome: Unexpected favorable outcome to sintilimab combined with chemotherapy
Authors: Liu Jiaying , Chang Xiaona , Xiao Guixiang , Zhong Jingmin , Huang Bo , Zhang Jiwei , Gao Beibei , Peng Gang , Nie Xiu 
Published: November 2022

BackgroundPatients with Lynch syndrome are at an increased risk of developing simultaneous or metachronous tumors, while sarcomas have been occasionally reported. Sarcomas are generally not considered part of the common Lynch syndrome tumor spectrum. However, more and more studies and case reports suggested that sarcoma could be a rare clinical manifestation of Lynch syndrome, leading to new treatment strategies for sarcoma.Case summaryWe report the case of a 74-year-old male patient with Lynch syndrome who had rectal mucinous adenocarcinoma and prostate adenocarcinoma and then developed undifferentiated sarcoma of the left neck two years later. Mismatch repair deficiency (dMMR) was confirmed by immunohistochemical staining for the mismatch repair proteins MSH2, MSH6, MLH1 and PMS2. The result of polymerase chain reaction (PCR) microsatellite instability (MSI) testing of sarcoma showed high-level microsatellite instability (MSI-H). Additionally, a pathogenic germline mutation in MSH2 (c.2459-12A&gt;G) was detected by next-generation sequencing (NGS). Taking into account HE morphology, immunohistochemical phenotype, MSI status, NGS result, medical history and germline MSH2 gene mutation, the pathological diagnosis of left neck biopsy tissue was Lynch syndrome related undifferentiated sarcoma with epithelioid morphology. The patient has been receiving immunotherapy (sintilimab) combined with chemotherapy (tegafur, gimeracil and oteracil potassium capsules) and currently has stable disease. We also reviewed the literature to understand the association between sarcoma and Lynch syndrome.ConclusionSarcoma may now be considered a rare clinical manifestation of Lynch syndrome. Attention and awareness about the association between Lynch syndrome and sarcoma need to be increased. Therefore, timely detection of MMR proteins and validation at the gene level for suspicious patients are the keys to avoiding missed or delayed diagnosis and to identifying patients suited for immunotherapy, which may also help to provide appropriate genetic counseling and follow-up management for patients.
Data-driven support to decision-making in molecular tumour boards for lymphoma: A design science approach
Authors: Rodríguez Ruiz Núria , Abd Own Sulaf , Ekström Smedby Karin , Eloranta Sandra , Koch Sabine , Wästerlid Tove , Krstic Aleksandra , Boman Magnus 
Published: November 2022

BackgroundThe increasing amount of molecular data and knowledge about genomic alterations from next-generation sequencing processes together allow for a greater understanding of individual patients, thereby advancing precision medicine. Molecular tumour boards feature multidisciplinary teams of clinical experts who meet to discuss complex individual cancer cases. Preparing the meetings is a manual and time-consuming process.PurposeTo design a clinical decision support system to improve the multimodal data interpretation in molecular tumour board meetings for lymphoma patients at Karolinska University Hospital, Stockholm, Sweden. We investigated user needs and system requirements, explored the employment of artificial intelligence, and evaluated the proposed design with primary stakeholders.MethodsDesign science methodology was used to form and evaluate the proposed artefact. Requirements elicitation was done through a scoping review followed by five semi-structured interviews. We used UML Use Case diagrams to model user interaction and UML Activity diagrams to inform the proposed flow of control in the system. Additionally, we modelled the current and future workflow for MTB meetings and its proposed machine learning pipeline. Interactive sessions with end-users validated the initial requirements based on a fictive patient scenario which helped further refine the system.ResultsThe analysis showed that an interactive secure Web-based information system supporting the preparation of the meeting, multidisciplinary discussions, and clinical decision-making could address the identified requirements. Integrating artificial intelligence via continual learning and multimodal data fusion were identified as crucial elements that could provide accurate diagnosis and treatment recommendations.ImpactOur work is of methodological importance in that using artificial intelligence for molecular tumour boards is novel. We provide a consolidated proof-of-concept system that could support the end-to-end clinical decision-making process and positively and immediately impact patients.ConclusionAugmenting a digital decision support system for molecular tumour boards with retrospective patient material is promising. This generates realistic and constructive material for human learning, and also digital data for continual learning by data-driven artificial intelligence approaches. The latter makes the future system adaptable to human bias, improving adequacy and decision quality over time and over tasks, while building and maintaining a digital log.
“Finding my way in a maze while the clock is ticking”: The daily life challenges of adolescents and young adults with an uncertain or poor cancer prognosis
Authors: Burgers Vivian W. G. , van den Bent Martin J. , Dirven Linda , Lalisang Roy I. , Tromp Jacqueline M. , Compter Annette , Kouwenhoven Mathilde , Bos Monique E. M. M. , de Langen Adrianus , Reuvers Milou J. P. , Franssen Suzanne A. , Frissen Simone A. M. M. , Harthoorn Niels C. G. L. , Dickhout Annemiek , Noordhoek Marloes J. , van der Graaf Winette T. A. , Husson Olga 
Published: November 2022

IntroductionIncreasingly more adolescent and young adult (AYA, aged 18–39 years) patients with an uncertain and/or poor cancer prognosis (UPCP) are gaining life-years because of novel treatments or refinement of established therapies, and sometimes even face the prospect of long-term disease control. This study aims to examine the challenges of AYAs with a UPCP in daily life to inform the development of AYA care programs.MethodsSemi-structured in-depth interviews were conducted among AYAs with a UPCP. Since we expected differences in experiences between three AYA subgroups, we interviewed patients of these subgroups (1): traditional survivors (2), low-grade glioma survivors, and (3) new survivors. Interviews were analyzed using elements of grounded theory. AYA patients were actively involved as research partners.ResultsIn total 46 AYAs with UPCP participated and shared their challenges in daily life. They were on average 33.4 years old (age range 23–44) and most of them were women (63%). The most common tumor types were low-grade gliomas (16), sarcomas (7), breast cancers (6), and lung cancers (6). We identified five primary themes: (1) feeling inferior to previous self and others (e.g. feeling useless, who wants me in a relationship), (2) feeling of being alone (e.g. lonely thoughts, nobody really gets me), (3) ongoing confrontation (e.g. it is always there, own decline), (4) grief about life (e.g. grief about life I did not get, grief about old life), and (5) loss of control over the future (e.g. not able to make future plans, waiting for growth). Although all of the challenges were identified in the three AYA subgroups, the perceived intensity of the challenges differed slightly between the subgroups.DiscussionAYAs living with a UPCP experience challenges associated to their sense of altered identity, their position in the social network, and the future uncertainties. This study highlights the importance to recognize and acknowledge the unique challenges of this group. To provide age-specific care, it is important to embed acceptance and commitment therapy and AYA peer support within the healthcare system and other care programs to support AYAs to live well with their disease.
Effects of new antiseizure medication on bone metabolism and bone mineral density in children: A meta-analysis
Authors: Zhuo La , Zhang Yong 
Published: November 2022

ObjectiveTo explore the effect of new antiseizure medication on bone metabolism and bone mineral density in children.MethodsThe Chinese and English databases (PubMed, EMBASE, Cochrane Library, CNKI, Wanfang and VIP) were systematically searched for observational studies evaluating the effects of new antiseizure medication on bone metabolism and bone mineral density in children with epilepsy. The effects of new antiseizure medication on serum calcium, phosphorus, alkaline phosphatase, bone alkaline phosphatase, parathyroid hormone, 25-hydroxyvitamin D and bone mineral density in children were systematically evaluated.ResultsAfter systematic retrieval and screening, 12 studies with high literature quality (including 629 epileptic children and 627 control subjects) were included in the systematic evaluation. Meta-analysis showed that new antiseizure medication decreased bone mineral density (MD: −0.05, 95%CI, −0.09, −0.02;P = 0.004). From different kinds of antiseizure medication, levetiracetam can reduce blood phosphorus concentration in children (MD: −0.04; 95%CI, −0.07, −0.01). Oxcarbazepine increased serum alkaline phosphatase in children (MD:17.98; 95%CI, 10.43,25.53;P &lt; 0.00001), and the increase intensity was significantly higher than that of levetiracetam (MD: 7.66; 95%CI, 0.29, 15.02;P = 0.04). In addition, oxcarbazepine can cause a significant increase in parathyroid hormone in children (MD: 7.52; 95%CI, 3.37,11.66;P = 0.0004), and 25 - hydroxyvitamin D was reduced, and the difference was statistically significant (MD:−2.18; 95%CI, −3.23, −1.13;P = 0.00006). However, the effects of new antiseizure medication on serum calcium and bone alkaline phosphatase in children were not statistically significantConclusionNew antiseizure medication have different effects on bone metabolism and bone mineral density in children with epilepsy, and the effects of different types of new antiseizure medication are different.
Multi-omics analysis the differences of VOCs terpenoid synthesis pathway in maintaining obligate mutualism between Ficus hirta Vahl and its pollinators
Authors: Fan Songle , Jia Yongxia , Wang Rong , Chen Xiaoyong , Liu Wanzhen , Yu Hui 
Published: November 2022

InroductionVolatile organic compounds (VOCs) emitted by the receptive syconia ofFicusspecies is a key trait to attract their obligate pollinating fig wasps.Ficus hirtaVahl is a dioecious shrub, which is pollinated by a highly specialized symbiotic pollinator in southern China. Terpenoids are the main components of VOCs inF. hirtaand play ecological roles in pollinator attraction, allelopathy, and plant defense. However, it remains unclear that what molecular mechanism difference in terpenoid synthesis pathways between pre-receptive stage (A-phase) and receptive stage (B-phase) ofF. hirtasyconia.MethodsTranscriptome, proteome and Gas Chromatography-Mass Spectrometer (GC-MS) were applied here to analyze these difference.Results and discussion:Compared to A-phase syconia, the genes (ACAT2,HMGR3,GGPS2,HDR,GPS2,TPS2,TPS4,TPS10-4,TPS14) related to the terpenoid synthesis pathway had higher expression level in receptive syconia (B-phase) according to transcriptome sequencing. Seven differentially expressed transcription factors were screened, namelybHLH7,MYB1R1,PRE6,AIL1,RF2b,ANT,VRN1. Specifically,bHLH7was only specifically expressed in B-phase. 235 differentially expressed proteins (DEPs) were mainly located in the cytoplasm and chloroplasts. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the DEPs were mainly enriched in the metabolic process. A total of 9 terpenoid synthesis proteins were identified in the proteome. Among them, 4 proteins in methylerythritol phosphate (MEP) pathway were all down-regulated. Results suggested the synthesis of terpenoids precursors in B-phase bracts were mainly accomplished through the mevalonic acid (MVA) pathway in cytoplasm. Correlation analysis between the transcriptome and proteome, we detected a total of 1082 transcripts/proteins, three of which are related to stress. From the VOCs analysis, the average percent of monoterpenoids emitted by A-phase and B-phase syconia were 8.29% and 37.08%, while those of sesquiterpenes were 88.43% and 55.02% respectively. Monoterpenes (camphene, myrcene, camphor, menthol) were only detected in VOCs of B-phase syconia. To attract pollinators, B-phase syconia ofF. hirtaneed more monoterpenoids and less sesquiterpenes. We speculate that transcription factorbHLH7may regulate the terpenoid synthesis pathway between A- and B-phase syconia. Our research provided the first global analysis of mechanism differences of terpenoid synthesis pathways between A and B phases inF. hirtasyconia.
Understanding the importance of motivational intensity in English as a foreign language context: A structural equation modeling analysis
Authors: Wang Cong , Zhu Sida , Zhang Haijing 
Published: November 2022

IntroductionMotivational intensity is the effort learners make in language learning. It is an essential component and a direct measurement of L2 motivation. Few studies have distinguished motivational intensity from motivation and explored its role in learning English as a foreign language (EFL).MethodsThis study examined 208 university students from Hong Kong to investigate the factors that affect motivational intensity and explored the relationship between motivational intensity and learning motivation using structural equation modeling (SEM).Results and discussionThe students’ motivational intensity was affected by personal factors (daily English-learning time and stage of English learning), family factors (monthly household income and parental attitudes), and school factors (English learning engagement and satisfaction). The differences in personal factors, school factors and monthly household income of family factors among different motivational intensity groups were significant whereas the difference in parental attitudes (family factors) between the high- and the low-motivational intensity groups was insignificant. As for the relationship between motivational intensity and motivation, motivational intensity indirectly affected students’ intrinsic interest through their attitudes toward native English speakers (β = 0.16, p = 0.041 &lt; 0.05). The significant path coefficient from the learning situation to attitudes toward native speakers was negative (p &lt; 0.05), indicating that attitudes toward native speakers decline even when the learning situation improves. This study enriched the theoretical study of motivation theory and provided teaching suggestions for improving EFL learning.
Association of Type D personality and mild cognitive impairment in patients with hypertension
Authors: Ye Qingfang , Liu Li , Wang Yini , Li Ling , Wang Zhengjun , Liu Guojie , Lin Ping , Li Qiujie 
Published: November 2022

ObjectiveThe aim of this study was to evaluate the association between Type D personality and mild cognitive impairment (MCI) in patients with hypertension.MethodsA total of 324 subjects with hypertension were included in the study. All of them completed questionnaires on demographic characteristics, Type D personality Scale, Montreal Cognitive Assessment (MoCA), Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI). The Type D personality effect was analyzed as both dichotomous and continuous methods.ResultsThe incidence of MCI was 56.5% in hypertensive individuals. Type D personality presenting as a dichotomous construct was an independent risk factor of MCI (odds ratio [OR] = 2.814, 95% confidence interval [CI] = 1.577–5.021, p &lt; 0.001), after adjusting for ages, sex and some clinical factors. Meanwhile, main effect of negative affectivity component was independently related to the prevalence of MCI (OR = 1.087, 95%CI = 1.014–1.165, p = 0.019). However, associations between the main effect of social inhibition component (OR = 1.011, 95%CI = 0.924–1.107, p = 0.811) as well as the interaction of negative affectivity and social inhibition (OR = 1.013, 95%CI = 0.996–1.030, p = 0.127) with MCI were not found.ConclusionThe findings suggest that Type D personality is strongly associated with MCI in patients with hypertension. The negative affectivity component of the Type D appears to drive the correlations between Type D and MCI. These findings provide new ideas for studying the mechanisms underlying the relationship between personality and cognitive decline in hypertensive individuals.