bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blockage of mechanosensitive Piezo1 channel alleviates the severity of experimental malaria-associated acute lung injury
Authors: Zhang Min , Wang Qian Ru , Hou Xinpeng , Wang Qi , Yang Xiaoyan , Zhou Tingting , Liu Xiaobo , Wu Lirong , Wang Jie , Jin Xiaobao , Liu Zhenlong , Huang Bo 
Published: February 2024

Abstract
Background
Malaria-associated acute lung injury (MA-ALI) is a well-recognized clinical complication of severe, complicated malaria that is partly driven by sequestrations of infected red blood cells (iRBCs) on lung postcapillary induced impaired blood flow. In earlier studies the mechanosensitive Piezo1 channel emerged as a regulator of mechanical stimuli, but the function and underlying mechanism of Piezo1 impacting MA-ALI severity via sensing the impaired pulmonary blood flow are still not fully elucidated. Thus, the present study aimed to explore the role of Piezo1 in the severity of murine MA-ALI.

Methods
Here, we utilized a widely accepted murine model of MA-ALI using C57BL/6 mice with Plasmodium berghei ANKA infection and then added a Piezo1 inhibitor (GsMTx4) to the model. The iRBC-stimulated Raw264.7 macrophages in vitro were also targeted with GsMTx4 to further explore the potential mechanism.

Results
Our data showed an elevation in the expression of Piezo1 and number of Piezo1+-CD68+ macrophages in lung tissues of the experimental MA-ALI mice. Compared to the infected control mice, the blockage of Piezo1 with GsMTx4 dramatically improved the survival rate but decreased body weight loss, peripheral blood parasitemia/lung parasite burden, experimental cerebral malaria incidence, total protein concentrations in bronchoalveolar lavage fluid, lung wet/dry weight ratio, vascular leakage, pathological damage, apoptosis and number of CD68+ and CD86+ macrophages in lung tissues. This was accompanied by a dramatic increase in the number of CD206+ macrophages (M2-like subtype), upregulation of anti-inflammatory cytokines (e.g. IL-4 and IL-10) and downregulation of pro-inflammatory cytokines (e.g. TNF-α and IL-1β). In addition, GsMTx4 treatment remarkably decreased pulmonary intracellular iron accumulation, protein level of 4-HNE (an activator of ferroptosis) and the number of CD68+-Piezo1+ and CD68+-4-HNE+ macrophages but significantly increased protein levels of GPX4 (an inhibitor of ferroptosis) in experimental MA-ALI mice. Similarly, in vitro study showed that the administration of GsMTx4 led to a remarkable elevation in the mRNA levels of CD206, IL-4, IL-10 and GPX-4 but to a substantial decline in CD86, TNF-α, IL-1β and 4-HNE in the iRBC-stimulated Raw264.7 cells.

Conclusions
Our findings indicated that blockage of Piezo1 with GsMTx4 alleviated the severity of experimental MA-ALI in mice partly by triggering pulmonary macrophage M2 polarization and subsequent anti-inflammatory responses but inhibited apoptosis and ferroptosis in lung tissue. Our data suggested that targeting Piezo1 in macrophages could be a promising therapeutic strategy for treating MA-ALI.

Graphical Abstract
Identification of DNA methylation biomarkers for evaluating cardiovascular disease risk from epigenome profiles altered by low-dose ionizing radiation
Authors: Park Jihye , Lee Hae-June , Han Yu Kyeong , Kang Keunsoo , Yi Joo Mi 
Published: February 2024

Abstract
Background
Environmental exposure, medical diagnostic and therapeutic applications, and industrial utilization of radionuclides have prompted a growing focus on the risks associated with low-dose radiation (< 100 mGy). Current evidence suggests that such radiation can induce epigenetic changes. Nevertheless, whether exposure to low-dose radiation can disrupt endothelial cell function at the molecular level is unclear. Because endothelial cells play crucial roles in cardiovascular health and disease, we aimed to investigate whether low-dose radiation could lead to differential DNA methylation patterns at the genomic level in endothelial cell (EC) lines.

Methods
We screened for changes in DNA methylation patterns in primary human aortic (HAECs) and coronary artery endothelial cells following exposure to low-dose ionizing radiation. Using a subset of genes altered via DNA methylation by low-dose irradiation, we performed gene ontology (GO) analysis to predict the possible biological network mediating the effect of low-dose radiation. In addition, we performed comprehensive validation using methylation and gene expression analyses, and ChIP assay to identify useful biomarkers among candidate genes for use in detecting low-dose radiation exposure in human primary normal ECs.

Results
Low-dose radiation is sufficient to induce global DNA methylation alterations in normal EC lines. GO analysis demonstrated that these hyper- or hypo-methylated genes were linked to diverse biological pathways. Our findings indicated a robust correlation between promoter hypermethylation and transcriptional downregulation of four genes (PGRMC1, UNC119B, RERE, and FNDC3B) in response to low-dose ionizing radiation in HAECs.

Conclusions
Based on these findings, the identified genes can serve as potential DNA methylation biomarkers for the assessment of cardiovascular risk upon exposure to low-dose radiation.
The Cambrian fossil Pikaia, and the origin of chordate somites
Authors: Lacalli Thurston 
Published: February 2024

AbstractThe Middle Cambrian fossil Pikaia has a regular series of vertical bands that, assuming chordate affinities, can be interpreted as septa positioned between serial myotomes. Whether Pikaia has a notochord and nerve cord is less certain, as the dorsal organ, which has no obvious counterpart in living chordates, is the only clearly defined axial structure extending the length of the body. Without a notochord to serve as a reference point, the location of the nerve cord is then conjectural, which begs the question of how a dorsal neural center devoted to somite innervation would first have arisen from a more diffuse ancestral plexus of intraepithelial nerves. This question is examined using hemichordates as a reference point, first for the information they provide on the organization of the ancestral deuterostome nervous system, and second, extending the analysis of E. E. Ruppert, to explain why neural infoldings like the enteropneust collar cord would first have evolved. Both implicate the medial surface of the anterior-most part of the metacoel as the likely site for the evolution of the first somites. The analysis highlights the importance of the somatobranchial condition in chordates, meaning the linkage between the anterior trunk, hox1 expression, and the beginning of the gill series and somites. This feature is arguably a valid criterion by which to assess extinct taxa from the Cambrian that resemble chordates (e.g., vetulicolians and yunnanozoans), but may be unrelated to them. In a more speculative vein, the nature of the dorsal organ is discussed, including the possibility that it is an expanded neural tube combining neural and support functions in one structure.
Chronic disease and multimorbidity in the Chinese older adults’ population and their impact on daily living ability: a cross-sectional study of the Chinese Longitudinal Healthy Longevity Survey (CLHLS)
Authors: Chen Ye , Ji Huixia , Shen Yang , Liu Dandan 
Published: February 2024

Abstract
Background
Owing to an increase in life expectancy, it is common for the older adults to suffer from chronic diseases that can result in disability and a low quality of life. This study aimed to explore the influence of chronic diseases and multimorbidities on activities of daily living (ADLs) and instrumental ADLs (IADLs) in an older Chinese population.

Methods
Based on the Chinese Longitudinal Healthy Longevity Survey (2018), 9,155 older adults aged 65 years and above were included in the study. A self-administered questionnaire was used to collect information on demographic characteristics, chronic diseases, ADLs, and IADLs. The impact of factors affecting ADL and IADL impairment in older adults was analysed using binary logistic regression.

Results
In total, 66.3% participants had chronic diseases. Hypertension, heart disease, arthritis, diabetes and cerebrovascular disease were among the top chronic diseases. Of these, 33.7% participants had multimorbidities. The most common combination of the two chronic diseases was hypertension and heart disease (11.2%), whereas the most common combination of the three chronic diseases was hypertension, heart disease, and diabetes (3.18%). After categorising the older adults into four age groups, dementia, visual impairment, and hearing impairment were found to be more prevalent with increasing age. The prevalence of hypertension, heart disease, cerebrovascular disease, gastrointestinal ulcers, arthritis and chronic nephritis gradually increased with age until the age of 75 years, peaked in the 75–84 years age group, and then showed a decreasing trend with age. Multimorbidity prevalence followed a similar pattern. Regression analysis indicated that the increase in age group and the number of chronic diseases independently correlated with impairments in ADL as well as IADL. Additionally, gender, physical activity, educational background, obesity, depressive symptoms, and falls also had an impact on ADLs or IADLs.

Conclusion
Chronic diseases and multimorbidities are common in older adults, and it is important to note that aging, multimorbidity, obesity, and unhealthy lifestyle choices may interfere with ADLs or IADLs in older adults. Therefore, it is imperative that primary healthcare providers pay special attention to older adults and improve screening for multimorbidity and follow-up needs.
Lung function and the risk of frailty in the European population: a mendelian randomization study
Authors: Zhou Rong , Tian Ge , Guo Xingzhi , Li Rui 
Published: February 2024

Abstract
Background
Epidemiological evidence has suggested a relationship between lung function and frailty, but the precise nature of the causality remains unclear. In this study, we applied a two-sample Mendelian randomization (MR) analysis to determine the causal effects of lung function on frailty.

Methods
Single nucleotide polymorphisms (SNPs) independently related (P ≤ 5E−08) to lung function, as identified by genome-wide association study (GWAS), were applied as instrumental variables (IV). The association with frailty index (FI) was investigated using summary-level data from the latest GWAS on FI (n = 175,226). Different statistical methods were employed to evaluate the causal estimates between lung function and FI. The pleiotropy, heterogeneity, and leave-one-out analysis were applied to confirm the stability of the MR estimates.

Results
Using the random-effect inverse-variance weighted approach, genetically proxied forced expiratory volume in the first second (FEV1), ratio of FEV1 on forced vital capacity (FVC) [FEV1/FVC], and peak expiratory flow (PEF) were significantly and inversely associated with FI (FEV1, β = −0.08, P = 2.03E−05; FEV1/FVC, β = −0.06, P = 9.51E−06; PEF, β = −0.07, P = 4.09E−04) with good statistical power (99.7–100%). However, no significant association was observed between FVC and FI (β = −0.01, P = 0.681). Leave-one-out analysis showed that there was no single SNP driving the bias of the estimates. There was potential heterogeneity, but no obvious pleiotropy was founded in this MR study.

Conclusions
Our findings indicate that impaired pulmonary function is closely related to the risk of frailty. Enhancing lung function in the elderly population may contribute to the prevention of frailty to a certain extent.
Drug-drug interaction assessment based on a large-scale spontaneous reporting system for hepato- and renal-toxicity, and thrombocytopenia with concomitant low-dose methotrexate and analgesics use
Authors: Honma Takeshi , Onda Kenji , Masuyama Koichi 
Published: February 2024

Abstract
Background
Methotrexate (MTX) is the cornerstone of rheumatoid arthritis (RA) treatment and is highly effective with low-dose intermittent administration. MTX is occasionally used in combination with non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen (APAP)/paracetamol for pain or inflammation control. With MTX treatment, the side effects, such as hepatotoxicity, renal failure, and myelosuppression should be considered. These are also seen with analgesics treatment.

Methods
We used a large spontaneously reported adverse event database (FAERS [JAPIC AERS]) to analyze whether the reporting of adverse events increased upon MTX and analgesic therapy in patients with RA.

Results
After identifying RA cases, the crude reporting odds ratios (cRORs) for hepatotoxicity, renal failure, and thrombocytopenia associated with the use of MTX, APAP, or NSAIDs were calculated by disproportionality analysis, which revealed significantly higher cRORs for these events. No analgesics showed consistent positive signals for drug-drug interaction (DDI) with concomitant low-dose MTX analyzed using four algorithms for DDI interaction (the Ω shrinkage measure, additive or multiplicative, and combination risk ratio models). However, in renal failure and thrombocytopenia, loxoprofen (Ω025 = 0.08) and piroxicam (Ω025 = 0.46), and ibuprofen (Ω025 = 0.74) and ketorolac (Ω025 = 3.52), respectively, showed positive signals in the Ω shrinkage measure model, and no consistency was found among adverse events or NSAIDs.

Conclusions
Studies using spontaneous reporting systems have limitations such as reporting bias or lack of patient background; however, the results of our comprehensive analysis support the results of previous clinical or epidemiological studies. This study also demonstrated the usefulness of FAERS for DDI assessment.
A HBIM pipeline for the conservation of large-scale architectural heritage: the city Walls of Pisa
Authors: Giuliani Francesca , Gaglio Francesca , Martino Massimiliano , De Falco Anna 
Published: February 2024

Abstract
In the architectural heritage field, a complete and in-depth knowledge of the assets is indispensable for any restoration and conservation strategy. In this context, the Historical Building Information Modelling (HBIM) technique is gaining much interest in supporting the diagnostic phase and the design and management of conservation activities. The HBIM provides opportunities to collect, organize and integrate information coming from different sources, inspections, and diagnosis techniques as well as to use standardized and effective tools for orienting cultural heritage asset management. This study addresses the challenges of developing HBIM for large-scale assets, that require adapting the conventional workflow to deliver results in a reasonable time. To this aim, a novel procedure involving a fit-for-purpose Inventory form and a scan-to-BIM approach is proposed. The data acquisition process is speeded up using multiple surveying techniques, and the modelling and information phases benefit from the interoperability among different tools that are already known by professionals in the field. As such, the main innovation lies in the ability to oversee the entire process through a single software, ensuring centralized and efficient control. This innovative process has been applied to investigate a significant portion of the city walls of Pisa, proving its ability to support the decision-making phase for planned conservation of large-scale architectural heritage. The emphasis is on the all-encompassing, interdisciplinary understanding of the assets across different scales. The suggested approach ensures a swift yet precise and reliable outcome in the diagnostic process and facilitating the critical temporal assessments and the review of information by any actor involved in the conservation.
CDK4/6 inhibitor-induced bone marrow micronuclei might be caused by cell cycle arrest during erythropoiesis
Authors: Okada Yuki , Chikura Satsuki , Kimoto Takafumi , Iijima Takeshi 
Published: February 2024

Abstract
Background
A micronucleus test is generally used to evaluate the genotoxic potential of chemicals. Exaggerated erythropoiesis, as occurs following bleeding, may induce an unexpected increase in micronucleus frequency. This false positive result would be typical in a genotoxicity study due to the enhanced progression of the cell cycle that restores decreased blood cells. The cyclin-dependent kinase (CDK) family is known to play an essential role in preventing genomic instability. Conversely, a selective CDK4/6 inhibitor PD0332991, clinically named Palbociclib, is reported to have genotoxic potential, shown by positive results in both in vitro and in vivo micronucleus studies. To clarify the mechanism by which cell cycle arrest induced by a CDK4/6 inhibitor increases micronucleus frequency, we investigated the positive results of the bone marrow micronucleus test conducted with PD0332991.

Results
Rats treated with PD0332991 exhibited increased micronucleus frequency in an in vivo bone marrow micronucleus test whereas it was not increased by treatment in human lymphoblastoid TK6 cells. In addition, all other genotoxicity tests including the Ames test and the comet assay showed negative results with PD0332991. Interestingly, PD0332991 treatment led to an increase in erythrocyte size in rats and affected the size distribution of erythrocytes, including the micronucleus. The mean corpuscular volume of reticulocytes (MCVr) in the PD0332991 treatment group was significantly increased compared to that of the vehicle control (83.8 fL in the PD0332991, and 71.6 fL in the vehicle control.). Further, the average micronucleated erythrocytes (MNE) size of the PD0332991 group and vehicle control was 8.2 and 7.3 µm, respectively. In the histogram, the vehicle control showed a monomodal distribution with a peak near 7.3 µm. In contrast, the PD0332991 group showed a bimodal distribution with peaks around 7.5 and 8.5 µm. Micronucleated erythrocytes in the PD0332991 group were significantly larger than those in the vehicle control.
These results suggest that the increase in micronucleus frequency induced by the CDK4/6 inhibitor is not due to genotoxicity, but is attributable to disturbance of the cell cycle, differentiation, and enucleation of erythroblasts.

Conclusions
It was suggested that the positive outcome of the in vivo bone marrow micronucleus test resulting from treatment with PD0332991 could not be attributed to its genotoxicity. Further studies to clarify the mechanism of action can contribute to the development of drug candidate compounds lacking intrinsic genotoxic effects.
CT-GCN+: a high-performance cryptocurrency transaction graph convolutional model for phishing node classification
Authors: Fu Bingxue , Wang Yixuan , Feng Tao 
Published: February 2024

AbstractDue to the anonymous and contract transfer nature of blockchain cryptocurrencies, they are susceptible to fraudulent incidents such as phishing. This poses a threat to the property security of users and hinders the healthy development of the entire blockchain community. While numerous studies have been conducted on identifying cryptocurrency phishing users, there is a lack of research that integrates class imbalance and transaction time characteristics. This paper introduces a novel graph neural network-based account identification model called CT-GCN+, which utilizes blockchain cryptocurrency phishing data. It incorporates an imbalanced data processing module for graphs to consider cryptocurrency transaction time. The model initially extracts time characteristics from the transaction graph using LSTM and Attention mechanisms. These time characteristics are then fused with underlying features, which are subsequently inputted into a combined SMOTE and GCN model for phishing user classification. Experimental results demonstrate that the CT-GCN+ model achieves a phishing user identification accuracy of 97.22% and a phishing user identification area under the curve of 96.67%. This paper presents a valuable approach to phishing detection research within the blockchain and cryptocurrency ecosystems.
Alternating hemiplegia of childhood misdiagnosed as hysteria: a case report
Authors: Wei Danlei , Lv Kang , He Jialinzi , Xiao Bo , Long Lili 
Published: February 2024

Abstract
Background
Alternating hemiplegia of childhood (AHC) is a rare pediatric syndrome characterized by recurring episodes of hemiplegia or quadriplegia, and frequently accompanied by dystonic posturing, choreoathetosis movements, anomalous ocular motions, and a gradual deterioration in cognitive function. The principal etiology of this disorder is traced back to mutations in the ATP1A3 gene.

Case presentation
Here, we report a 16-year-old girl with recurrent hemiplegia since her infancy. This patient has experienced paroxysmal limb weakness and aphasia for over 15 years, and has kept seeking medical attention but without receiving effective treatment. A misdiagnosis of hysteria persisted for over 4 years until the patient’s admission to our hospital. Whole-exome sequencing identified a known pathogenic heterozygous c.2270T>C (p.Leu757Pro) mutation in her ATP1A3 gene. Notably, her clinical manifestations, including pathological emotional responses and autonomic dysfunction, differed from the established profile associated with the same ATP1A3 mutation, which typically present with intellectual disability, a rostrocaudal symptom gradient, choreoathetosis, and dysarthria. The patient was finally diagnosed with AHC and treated with flunarizine thus significantly ameliorated hemiplegic episodes.

Conclusions
This case enhances our understanding of the intricate clinical manifestations of AHC, which require careful differentiation from various diseases such as epilepsy, hysteria, and paroxysmal dyskinesias. In the diagnosis of patients presenting with suspected symptoms, adhering to a systematic approach for localizing and diagnosing neurological disorders is crucial to prevent misdiagnosis and inappropriate treatments. Additionally, when AHC is suspected in a patient, genetic testing should be considered as part of the diagnostic approach.
Co-design of ‘Ways of Being’, a web-based experience to optimise online arts and culture for mental health in young people
Authors: Syed Sheriff Rebecca J. , Sinclair Eloise , Young Jen , Bhamra Sophia , Chandler Louise , Arachchige Tharuka , Adams Helen , Bonsaver Laura , Riga Evgenia , Bergin Laura , Mirtorabi Negin , Abuelgasim Leenah , Beuchner Hadassah , Geddes John 
Published: February 2024

Aims and methodWe aimed to co-design an intervention optimising the benefits of online arts and culture for mental health in young people for subsequent testing in a trial. Co-design followed the double diamond phases of design, discover, define, develop and deliver.ResultsNavigating the views of all co-designers to produce a testable resource demanded in-depth understanding, and frequent iterations in multiple modalities of the theoretical basis of the intervention, amplification of youth voice and commitment to a common goal.Clinical implicationsCo-design with a broad range of collaborators with a shared vision was valued by young co-designers and produced an effective intervention. Co-design allowed the theoretical basis to be followed and refined to create an engaging, practical and testable web experience, aiming to optimise the mental health benefits of online arts and culture for young people in a randomised controlled trial.