bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of PLK4 remodels histone methylation and activates the immune response via the cGAS-STING pathway in TP53-mutated AML
Authors: Man Cheuk-Him , Lam Wing , Dang Chee-Chean , Zeng Xiao-yuan , Zheng Li-Chuan , Chan Natalie Nok-Man , Ng Ka-Lam , Chan Koon-Chuen , Kwok Tsz-Ho , Ng Timothy Chi-Chun , Leung Wing-Yan , Huen Michael Shing-Yan , Wong Carmen Chak-Lui , So Chi Wai Eric , Dou Zhixun , Goyama Susumu , Bray Mark Robert , Mak Tak Wah , Leung Anskar Yu-Hung 
Published: September 2023

Abstract
Acute myeloid leukemia (AML) with TP53 mutation is one of the most lethal cancers and portends an extremely poor prognosis. Based on in silico analyses of druggable genes and differential gene expression in TP53-mutated AML, we identified pololike kinase 4 (PLK4) as a novel therapeutic target and examined its expression, regulation, pathogenetic mechanisms, and therapeutic potential in TP53-mutated AML. PLK4 expression was suppressed by activated p53 signaling in TP53 wild-type AML and was increased in TP53-mutated AML cell lines and primary samples. Short-term PLK4 inhibition induced DNA damage and apoptosis in TP53 wild-type AML. Prolonged PLK4 inhibition suppressed the growth of TP53-mutated AML and was associated with DNA damage, apoptosis, senescence, polyploidy, and defective cytokinesis. A hitherto undescribed PLK4/PRMT5/EZH2/H3K27me3 axis was demonstrated in both TP53 wild-type and mutated AML, resulting in histone modification through PLK4-induced PRMT5 phosphorylation. In TP53-mutated AML, combined effects of histone modification and polyploidy activated the cGAS-STING pathway, leading to secretion of cytokines and chemokines and activation of macrophages and T cells upon coculture with AML cells. In vivo, PLK4 inhibition also induced cytokine and chemokine expression in mouse recipients, and its combination with anti-CD47 antibody, which inhibited the “don’t-eat-me” signal in macrophages, synergistically reduced leukemic burden and prolonged animal survival. The study shed important light on the pathogenetic role of PLK4 and might lead to novel therapeutic strategies in TP53-mutated AML.
O-linked sialic acid residues on platelet membrane glycoprotein IIb mask the human HPA-9b alloepitope
Authors: Zhang Nanyan , Sullivan Mia J. , Curtis Brian R. , Newman Peter J. 
Published: September 2023

Abstract
Sialic acids occupy the terminal position of glycan chains and have the potential to influence the antigenicity of glycoproteins (GP). The polymorphisms of human platelet alloantigens (HPA)-3 and HPA-9, located near the C-terminus of the extracellular domain of platelet membrane GPIIb, are adjacent to sialyl-core 1 O-glycans emanating from serines 845 and 847. Whether the nearby O-glycans affect the antigenicity of HPA-9b or influence the binding of anti-HPA-9b alloantibodies in clinically significant cases of neonatal alloimmune thrombocytopenia is unknown. To address this issue, we generated a series of O-glycan mutant HPA-9 allele-specific induced pluripotent stem cell lines, differentiated them to megakaryocytes (MKs), and examined their ability to bind HPA-9b-specific alloantibodies. We found that both wild-type MKs treated with neuraminidase and those genetically modified to lack the sialidases ST3GAL1 and ST3GAL2 dramatically increased anti-HPA-9b alloantibody binding, indicating that the HPA-9b epitope is partially masked by terminal sialic acids on nearby O-glycans of GPIIb. Interestingly, mutating the serine residues that carry these glycan chains to alanine actually reduced the binding of anti-HPA-9b alloantibodies, indicating that these 2 O-glycan chains contribute to the presentation of the HPA-9b epitope—perhaps by stabilizing the conformation of the GP in this region. Collectively, our data suggest that detection of anti-HPA-9b alloantibodies may be enhanced through the use of HPA-9b-specific MKs that have been genetically altered to lack nearby terminal sialic acid residues but retain the glycan chains to which they are attached.
Tafasitamab and lenalidomide in large B-cell lymphoma: real-world outcomes in a multicenter retrospective study
Authors: Qualls David A. , Lambert Nicholas , Caimi Paolo F. , Merrill Mwanasha , Pullarkat Priyanka , Godby Richard C. , Bond David A. , Wehmeyer Graham T. , Romancik Jason , Amoozgar Behzad , Leslie Lori , Nastoupil Loretta J. , Crombie Jennifer L. , Abramson Jeremy S. , Khurana Arushi , Nowakowski Grzegorz S. , Maddocks Kami , Rutherford Sarah C. , Kahl Brad , Okwali Michelle , Buege Michael J. , Seshan Venkatraman , Batlevi Connie L. , Salles Gilles 
Published: September 2023

Abstract
In this real-world evaluation of tafasitamab-lenalidomide (TL) in relapsed or refractory LBCL, patients receiving TL had higher rates of comorbidities and high-risk disease characteristics, and substantially lower progression-free survival and overall survival, compared with the L-MIND registration clinical trial for TL.
TCRαβ/CD19 cell–depleted HLA-haploidentical transplantation to treat pediatric acute leukemia: updated final analysis
Authors: Merli Pietro , Algeri Mattia , Galaverna Federica , Bertaina Valentina , Lucarelli Barbarella , Boccieri Emilia , Becilli Marco , Quagliarella Francesco , Rosignoli Chiara , Biagini Simone , Girolami Elia , Meschini Antonella , Del Principe Giovanna , Sborgia Raffaella , Catanoso Maria Luigia , Carta Roberto , Strocchio Luisa , Pinto Rita Maria , Buldini Barbara , Falco Michela , Meazza Raffaella , Pende Daniela , Andreani Marco , Li Pira Giuseppina , Pagliara Daria , Locatelli Franco 
Published: September 2023

Abstract
TCRαβ/CD19 cell depletion is a promising graft manipulation technique frequently used in the context of human leukocyte antigen (HLA)–haploidentical hematopoietic stem cell transplantation (HSCT). We previously reported the results of a phase I-II clinical trial (NCT01810120) to assess the safety and the efficacy of this type of exvivo T-cell depletion in 80 children with acute leukemia, showing promising survival outcomes. We now report an updated analysis on a cohort of 213 children with a longer follow-up (median, 47.6 months for surviving patients). With a 5-year cumulative incidence of nonrelapse mortality of 5.2% (95% confidence interval [CI], 2.8%-8.8%) and a cumulative incidence of relapse of 22.7% (95% CI, 16.9%-29.2%), projected 10-year overall and disease-free survival (DFS) were 75.4% (95% CI, 68.6%-80.9%) and 71.6% (95% CI, 64.4%-77.6%), respectively. Cumulative incidence of both grade II-IV acute and chronic graft-versus-host disease were low (14.7% and 8.1%, respectively). In a multivariable analysis for DFS including type of disease, use of total body irradiation in the conditioning regimen (hazard ratio [HR], 0.5; 95% CI, 0.26-0.98; P = .04), disease status at HSCT (complete remission [CR] ≥3 vs CR 1/2; HR, 2.23; 95% CI, 1.20-4.16; P = .01), and high levels of pre-HSCT minimal residual disease (HR, 2.09; 95% CI, 1.01-4.33; P = .04) were independently associated with outcome. In summary, besides confirming the good outcome results already reported (which are almost superimposable on those of transplant from HLA-matched donors), this clinical update allows the identification of patients at higher risk of treatment failure for whom personalized approaches, aimed at reducing the risk of relapse, are warranted.
Mid-Cretaceous extensional magmatism in the Alborz Mountains, north Iran; geochemistry and geochronology of Gasht-Masuleh gabbros
Authors: Rezaei Leila , Timmerman Martin J. , Moazzen Mohssen , Altenberger Uwe , Sláma Jiří , Sudo Masafumi , Günter Christina , Wilke Franziska D. H. , Schleicher Anja M. 
Published: September 2023

AbstractIn the Gasht-Masuleh area in the Alborz Mountains, gabbroic magma intruded Palaeozoic metasediments and Mesozoic sediments and crystallised as isotropic and cumulate gabbros. LREE enrichment points to relatively low degrees of mantle melting and depletion of Ti, Nb and Ta relative to primitive mantle points to an arc related component in the magma. Clinopyroxene compositions indicate MORB to arc signatures. U–Pb zircon crystallisation ages of 99.5 ± 0.6 Ma and 99.4 ± 0.6 Ma and phlogopite 40Ar/39Ar ages of 97.1 ± 0.4 Ma, 97.5 ± 0.4 Ma, 97.1 ± 0.1 Ma, within 2σ error, indicate that gabbro intrusion occurred in the (Albian-)Cenomanian (mid-Cretaceous). As active subduction did not take place in the Cretaceous in North Iran, the small volume mafic magmatism in the Gasht-Masuleh area must be due to local, extension-related mantle melting. Melting was most likely caused by far field effects triggered by roll-back of the Neo-Tethys subducting slab. As subduction took place at a distance of ~ 400 km (present distance) from the Alborz Mountains, the observed arc geochemical signatures must be inherited from a previous subduction event and concomitant mantle metasomatism, possibly in combination with contamination of the magma by crustal material.
Aerobic exercise improves cognitive impairment in mice with type 2 diabetes by regulating the MALAT1/miR-382-3p/BDNF signaling pathway in serum-exosomes
Authors: Wang Mingzhu , Xie Kangling , Zhao Shengnan , Jia Nan , Zong Yujiao , Gu Wenping , Cai Ying 
Published: September 2023

Abstract
Background
It has been documented that aerobic exercise (AE) has a positive effect on improving cognitive function in type 2 diabetes (T2DM) patients. Here, we tried to explore how AE regulates the expression of long non-coding RNA in serum-exosomes (Exos), thereby affecting cognitive impairment in T2DM mice as well as its potential molecular mechanism.

Methods
T2DM mouse models were constructed, and serum-Exos were isolated for whole transcriptome sequencing to screen differentially expressed lncRNA and mRNA, followed by prediction of downstream target genes. The binding ability of miR-382-3p with a long non-coding RNA MALAT1 and brain-derived neurotrophic factor (BDNF) was explored. Then, primary mouse hippocampal neurons were collected for in vitro mechanism verification, as evidenced by the detection of hippocampal neurons' vitality, proliferation, and apoptosis capabilities, and insulin resistance. Finally, in vivo mechanism verification was performed to assess the effect of AE on insulin resistance and cognitive disorder.

Results
Transcriptome sequencing analysis showed that MALAT1 was lowly expressed and miR-382-3p was highly expressed in serum-Exos samples of T2DM mice. There were targeted binding sites between MALAT1 and miR-382-3p and between miR-382-3p and BDNF. In vitro experiments showed that MALAT1 upregulated BDNF expression by inhibiting miR-382-3p. Silencing MALAT1 or overexpressing miR-382-3p could reduce the expression of INSR, IRS-1, IRS-2, PI3K/AKT, and Ras/MAPK, inhibit neuronal proliferation, and promote apoptosis. In vivo experiments further confirmed that AE could increase the expression of MALAT1 in serum-Exos to competitively inhibit miR-382-3p and upregulate BDNF expression, thereby improving cognitive impairment in T2DM mice.

Conclusion
AE may upregulate the expression of MALAT1 in serum-Exos to competitively inhibit miR-382-3p and upregulate BDNF expression, thus improving cognitive impairment in T2DM mice.
Identification of plant vacuole proteins by using graph neural network and contact maps
Authors: Sui Jianan , Chen Jiazi , Chen Yuehui , Iwamori Naoki , Sun Jin 
Published: September 2023

AbstractPlant vacuoles are essential organelles in the growth and development of plants, and accurate identification of their proteins is crucial for understanding their biological properties. In this study, we developed a novel model called GraphIdn for the identification of plant vacuole proteins. The model uses SeqVec, a deep representation learning model, to initialize the amino acid sequence. We utilized the AlphaFold2 algorithm to obtain the structural information of corresponding plant vacuole proteins, and then fed the calculated contact maps into a graph convolutional neural network. GraphIdn achieved accuracy values of 88.51% and 89.93% in independent testing and fivefold cross-validation, respectively, outperforming previous state-of-the-art predictors. As far as we know, this is the first model to use predicted protein topology structure graphs to identify plant vacuole proteins. Furthermore, we assessed the effectiveness and generalization capability of our GraphIdn model by applying it to identify and locate peroxisomal proteins, which yielded promising outcomes. The source code and datasets can be accessed at https://github.com/SJNNNN/GraphIdn.
Genic constraint against nonsynonymous variation across the mouse genome
Authors: Powell George , Simon Michelle M. , Pulit Sara , Mallon Ann-Marie , Lindgren Cecilia M. 
Published: September 2023

Abstract
Background
Selective constraint, the depletion of variation due to negative selection, provides insights into the functional impact of variants and disease mechanisms. However, its characterization in mice, the most commonly used mammalian model, remains limited. This study aims to quantify mouse gene constraint using a new metric called the nonsynonymous observed expected ratio (NOER) and investigate its relationship with gene function.

Results
NOER was calculated using whole-genome sequencing data from wild mouse populations (Mus musculus sp and Mus spretus). Positive correlations were observed between mouse gene constraint and the number of associated knockout phenotypes, indicating stronger constraint on pleiotropic genes. Furthermore, mouse gene constraint showed a positive correlation with the number of pathogenic variant sites in their human orthologues, supporting the relevance of mouse models in studying human disease variants.

Conclusions
NOER provides a resource for assessing the fitness consequences of genetic variants in mouse genes and understanding the relationship between gene constraint and function. The study’s findings highlight the importance of pleiotropy in selective constraint and support the utility of mouse models in investigating human disease variants. Further research with larger sample sizes can refine constraint estimates in mice and enable more comprehensive comparisons of constraint between mouse and human orthologues.
Comparative pangenomic analysis of predominant human vaginal lactobacilli strains towards population-specific adaptation: understanding the role in sustaining a balanced and healthy vaginal microenvironment
Authors: Bhattacharya Anupam , Das Sushmita , Bhattacharjee Maloyjo Joyraj , Mukherjee Ashis K. , Khan Mojibur Rohman 
Published: September 2023

AbstractThe vaginal microenvironment of healthy women has a predominance of Lactobacillus crispatus, L. iners, L. gasseri, and L. jensenii. The genomic repertoire of the strains of each of the species associated with the key attributes thereby regulating a healthy vaginal environment needs a substantial understanding.We studied all available human strains of the four lactobacilli across different countries, isolated from vaginal and urinal sources through phylogenetic and pangenomic approaches. The findings showed that L. iners has the highest retention of core genes, and L. crispatus has more gene gain in the evolutionary stratum. Interestingly, L. gasseri and L. jensenii demonstrated major population-specific gene-cluster gain/loss associated with bacteriocin synthesis, iron chelating, adherence, zinc and ATP binding proteins, and hydrolase activity. Gene ontology enrichment analysis revealed that L. crispatus strains showed greater enrichment of functions related to plasma membrane integrity, biosurfactant, hydrogen peroxide synthesis, and iron sequestration as an ancestral derived core function, while bacteriocin and organic acid biosynthesis are strain-specific accessory enriched functions. L. jensenii showed greater enrichment of functions related to adherence, aggregation, and exopolysaccharide synthesis. Notably, the key functionalities are heterogeneously enriched in some specific strains of L. iners and L. gasseri.This study shed light on the genomic features and their variability that provides advantageous attributes to predominant vaginal Lactobacillus species maintaining vaginal homeostasis. These findings evoke the need to consider region-specific candidate strains of Lactobacillus to formulate prophylactic measures against vaginal dysbiosis for women’s health.
GhIMP10D, an inositol monophosphates family gene, enhances ascorbic acid and antioxidant enzyme activities to confer alkaline tolerance in Gossypium hirsutum L.
Authors: Fan Yapeng , Peng Fanjia , Cui Ruifeng , Wang Shuai , Cui Yupeng , Lu Xuke , Huang Hui , Ni Kesong , Liu Xiaoyu , Jiang Tiantian , Feng Xixian , Liu Mengyue , Lei Yuqian , Chen Wenhua , Meng Yuan , Han Mingge , Wang Delong , Yin Zujun , Chen Xiugui , Wang Junjuan , Li Yujun , Guo Lixue , Zhao Lanjie , Ye Wuwei 
Published: September 2023

Abstract
Background
Inositol monophosphates (IMP) are key enzymes in the ascorbic acid (AsA) synthesis pathways, which play vital roles in regulating plant growth and development and stresses tolerance. To date, no comprehensive analysis of the expression profile of IMP genes and their functions under abiotic stress in cotton has been reported.

Results
In this study, the genetic characteristics, phylogenetic evolution, cis-acting elements and expression patterns of IMP gene family in cotton were systematically analyzed. A total of 28, 27, 13 and 13 IMP genes were identified in Gossypium hirsutum (G. hirsutum), Gossypium barbadense (G. barbadense), Gossypium arboreum (G. arboreum), and Gossypium raimondii (G. raimondii), respectively. Phylogenetic analysis showed that IMP family genes could cluster into 3 clades. Structure analysis of genes showed that GhIMP genes from the same subgroup had similar genetic structure and exon number. And most GhIMP family members contained hormone-related elements (abscisic acid response element, MeJA response element, gibberellin response element) and stress-related elements (low temperature response element, defense and stress response element, wound response element). After exogenous application of abscisic acid (ABA), some GhIMP genes containing ABA response elements positively responded to alkaline stress, indicating that ABA response elements played an important role in response to alkaline stress. qRT-PCR showed that most of GhIMP genes responded positively to alkaline stress, and GhIMP10D significantly upregulated under alkaline stress, with the highest up-regulated expression level. Virus-induced gene silencing (VIGS) experiment showed that compared with 156 plants, MDA content of pYL156:GhIMP10D plants increased significantly, while POD, SOD, chlorophyII and AsA content decreased significantly.

Conclusions
This study provides a thorough overview of the IMP gene family and presents a new perspective on the evolution of this gene family. In particular, some IMP genes may be involved in alkaline stress tolerance regulation, and GhIMP10D showed high expression levels in leaves, stems and roots under alkaline stress, and preliminary functional verification of GhIMP10D gene suggested that it may regulate tolerance to alkaline stress by regulating the activity of antioxidant enzymes and the content of AsA. This study contributes to the subsequent broader discussion of the structure and alkaline resistance of IMP genes in cotton.
Traumatic life events and risk for dementia: a systematic review and meta-analysis
Authors: Severs Emilia , James Tiffeny , Letrondo Pilar , Løvland Lise , Marchant Natalie L. , Mukadam Naaheed 
Published: September 2023

Abstract
Objectives
To systematically review the association between traumatic life events (TLE) and dementia risk.

Design
Systematic review and meta-analysis.

Data sources
APA, PsychINFO, Embase and MEDLINE from their inception to 29.05.21 and updated on 20.04.22.

Eligibility criteria for selecting studies
Original research articles published in peer reviewed journals examining the association between TLE and all cause dementia in individuals aged 60 and over. Two researchers independently assessed the risk of bias using the Newcastle–Ottawa Scale. We conducted a generic inverse variance random effects meta-analysis to provide an overall estimate of TLE impact on dementia risk.

Main outcome measures
Risk, odds and hazards ratios relating to dementia risk.

Results
Initially, 3,487 studies were retrieved in the search and seven studies were included in the meta-analysis with data being used from 276,570 participants. TLE were associated with increased dementia risk. Trauma in general had a pooled HR of 1.21, (95% CI 1.03, 1.43, P = 0.0001). War/ Holocaust trauma and childhood trauma were also associated with increased dementia risk (HR = 1.28 (95% CI 1.01–1.63, P = 0.02) and HR = 1.76 (95% CI 1.17–2.64, P = 0.007) respectively).

Conclusions
We have found an association between TLE and dementia risk. Future research exploring the dimensions of TLE and individual level factors are needed to better understand the relationship between TLE and dementia.

Trial Registration
PROSPERO CRD42021253090.
Survey of knowledge, self-efficacy, and attitudes toward suicide prevention among nursing staff
Authors: Huang Kuan Chin , Jeang Shiow-Rong , Hsieh Hsing-Ling , Chen Jing-Wen , Yi Ching-Hsien , Chiang Yung-Chih , Wu Han-Ping 
Published: September 2023

Abstract
Objective
This study aimed to explore the knowledge, self-efficacy, and attitudes toward suicide prevention among nurses with different demographic characteristics.

Methods
A cross-sectional descriptive design was adopted, and the study was conducted between August and September 2020. The content of the questionnaire included basic demographics, knowledge, self-efficacy, and attitudes toward suicide prevention. Correlation analysis was performed to determine nurses’ knowledge, self-efficacy, and attitudes toward suicide prevention.

Results
The sample comprised 778 nursing staff from a medical center in southern Taiwan. The results showed that age, years of nursing experience, department type, education on suicide prevention, and care experience of nursing staff were associated with their knowledge, self-efficacy, and attitudes toward suicide prevention in general hospital patients. Younger and less experienced nurses demonstrated superior knowledge, self-efficacy, and attitudes toward suicide prevention. Nurses who received suicide-related education and training exhibited better self-efficacy and attitudes than those who did not. Nurses with care experience had better knowledge of suicide prevention than those without experience. Knowledge and self-efficacy in suicide prevention were both significantly and positively correlated with attitudes.

Conclusion
Younger, less experienced, psychiatric nurses demonstrated superior knowledge, self-efficacy, and attitudes toward suicide prevention. Therefore, education on suicide prevention should be strengthened for older, experienced, and non-psychiatric nurses.