bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disulfidptosis and pentose phosphate pathway-associated prognosis signature guides immunotherapy for lung adenocarcinoma patients
Authors: Zhou hanyu , yun xiao , wu jun , Wang xinzhu 
Published: October 2024

Abstract

Background
Disulfidptosis is a form of cell death, where generation of nicotinamide adenine dinucleotide phosphate (NADPH) through the pentose phosphate pathway (PPP) play an important role. The discovery of disulfidptosis provides new in-sights into lung adenocarcinoma (LUAD) therapeutics.
Research Design and Methods:
Disulfidptosis regulators (DSRs) was used to identify subgroups. Meanwhile, WGCNA and single-cell analysis were performed to identify genes related to disulfidptosis and PPP (DPRGs). To determine the risk signature, clinical features were analyzed, as well as prognostic pre-dictive ability, tumor immune microenvironment (TIME), immunotherapeutic response and drug sensitivity. Finally, the results were experimentally verified in vitro and vivo.
Results
We identified two DSR and DPRG clusters associated with distinct immune profiles involved in regulating different biological processes. The risk signature was effective in assessing LUAD prognosis in patients. It showed a strong correlation with TIME and could predict the immunotherapy response. After LRRC61 knockdown, the proliferation, migration and anti-apoptotic ability of LUAD cells were significantly reduced. Moreover, the xenograft tumors showed tumour growth was promoted when overexpressing LRRC61.
Conclusion
We analyzed DSRs and DPRGs in LUAD and developed an evaluation system that assesses the risk and guides the clinical application of drugs, including chemotherapeutic and immunotherapeutic agents.
From genomic to panomic predictions: An intuitive PANOMICs platform utilizing advanced Machine Learning algorithms
Authors: Schwarzerova Jana , Nohel Michal , Sitkova Radka , Skarda Jozef , Provaznik Valentine , Waldherr Steffen , Nägele Thomas , Chmelik Jiri , Walther Dirk , Weckwerth Wolfram 
Published: October 2024

Abstract

Advanced sequencing techniques have propelled molecular biology research into what is often termed the post-genomics era. Consequently, there is a heightened focus on unraveling the functional connections between individual genes and their ultimate phenotype, an area referred to as predictive genomics. To support this quest, we developed an intuitive platform, PANOMICS, that we believe substantially facilitates the statistical model building to pathway inference, with applications ranging from agriculture to the biomedical field.
PANOMICS, designed using Matlab2023b App Designer, allows for the uploading of genomics data, such as Single Nucleotide Polymorphisms (SNPs) information, metabolomics, other omics data, and phenotype information. The integration of different omics layers for the prediction of phenotypic outcomes promises to improve the accuracy and shifts the original genomic prediction, based solely on genomic inforamtion, to panomic prediction, that integrates multiple layers of molecular organization. PANOMICS facilitates data visualization and predictive analysis using various approaches and methods, such as linear, non-linear, and deep learning approaches. These analyses include statistical prediction models calculated based on Least Absolute Shrinkage and Selection Operator (LASSO), Ridge Regression (RR), Elastic Net Regression (ENR), Gaussian Process Regression (GPR), Support Vector Regression (SVR), Partial Least Squares (PLS) regression, and Random Forest (RF), as well as sophisticated Long Short-Term Memory (LSTM) and Convolutional Neural Network (CNN) models. Genome-Wide Association Studies (GWAS) with visualization based on an implementation of mixed linear models such as Ridge Regression with Best Linear Unbiased Prediction (rrBLUP) and Polygenic Risk Scores (PRS) are all put into practice within the app. The integration of a full range of advanced techniques within the application enhances its utility for researchers aiming to identify and interpret complex genetic interactions. This can lead to a more efficient use of Machine Learning (ML) algorithms in fields ranging from agriculture to medicine.
Polyfunctional immunity and transcriptional imprint associated with protection by chimeric live-attenuated Zika virus vaccine in non-human primates
Authors: Dallmeier Kai , Ma Ji , Malengier-Devlies Bert , Verstrepen Babs , Alpizar Yeranddy , Vercruysse Thomas , Javarappa Mahadesh , Sanchez-Felipe Lorena , Koopmans Gerrit , de Groot Natasja , Matthys Patrick , Neyts Johan , Verschoor Ernst , Coelmont Lotte , Thibaut Hendrik Jan , Weyenbergh Johan Van 
Published: October 2024

Abstract

Though generally mild in humans, Zika virus (ZIKV) frequently causes severe disease and congenital defects in children born to mothers infected during pregnancy (Musso et al. NEJM 2019 PMID: 31597021; Shan et al. Cell Host Microbe 2018 PMID: 30008291). Previously, chimeric candidate vaccine YF-ZIK was shown to protect mice against lethal ZIKV infection and congenital malformations after single-dose immunization (Kum et al. npj Vaccines 2018 PMID: 30564463; Kum et al. Emerg. Microbes Infect. 2020 PMID: 32116148). Here we demonstrate that YF-ZIK is safe, induces strong antiviral immunity, and protects rhesus macaques against vigorous experimental challenge. YF-ZIK triggered within 7-14 days after a single subcutaneous dose high levels of neutralizing antibodies, which could significantly be boosted by a second immunization 4 weeks later. Passively transferred immune serum protects AG129 mice from lethal ZIKV challenge, supporting neutralizing antibodies as major correlate of protection. Humoral immunity is complemented by ZIKV-specific cellular responses, characterized by a balanced Th1/Th2 cytokine production. Transcriptional analyses demonstrate the induction of a gene expression profile that is comparable to that of the original yellow fever YF17D vaccine, involving multiple pathways favoring polyvalent immunity. When YF-ZIK vaccinated macaques were challenged with a high intradermal dose of ZIKV, viral RNA remains undetectable in most animals. Immunity may be sterilizing immunity as no elevation of ZIKV neutralizing antibodies, nor seroconversion to anti-ZIKV NS1 antibodies was evident. Protection is associated with an activation of innate and adaptive immunity early after challenge. Systems analysis unveils B-cell receptor TNFRSF17 as predictor for strong antibody responses to YF-ZIK vaccination in common with YF17D (Gaucher et al. J. Exp. Med. 2008 PMID: 19047440; Querec et al. Nat. Immunol. 2009 PMID: 19029902; Fourati et al. Nat. Immunol. 2022 PMID: 36316476 ), along with GNAS and CD207 (Langerin) as novel biomarkers predicting clinical outcomes. The favorable preclinical safety, immunogenicity and efficacy of YF-ZIK justifies future evaluation in humans.
Collateral benefits of ivermectin MDA designed for malaria against headlice in Mopeia, Mozambique: a cluster randomised controlled trial
Authors: Furnival-Adams Joanna , Houana Amelia , Nicolas Patricia , Montaña Julia , Martinho Samuel , Casellas Aina , Mundaca Hansel , Mbanze Jenisse , Soares Arlindo , Imputiua Saimado , Ruiz-Castillo Paula , Ribes Marta , Sanz Almudena , Sale Mussa Mamudo , Macucha Antonio , Elobolobo Eldo , Vegove Vegovito , Mutepa Victor , Munguambe Humberto , Xerinda Aida , Materula Felisbela , Rabinovich Regina , Saute Francisco , Chaccour Carlos 
Published: October 2024

Abstract

Background
Headlice are prevalent worldwide, with a higher burden in rural, lower-middle income settings. They can cause intense itchiness, discomfort, and secondary bacterial infections with potentially serious consequences. Ivermectin is known to be efficacious against headlice, and is also currently being evaluated as a malaria vector control tool. In this study, we explored risk factors for headlice, and assessed the efficacy of ivermectin mass drug administration designed for malaria against headlice.
Methods
We conducted an open-label, assessor-blind, cluster-randomized controlled trial in Mopeia, Mozambique. A single dose of ivermectin was given monthly to eligible humans or humans and livestock (humans: 400 ug/kg, livestock: 1% injectable 200 ug/kg) in 3 consecutive months during the rainy season. The control group received albendazole (humans only). 39 clusters (13 per arm) were randomly selected for the nested assessment of headlice prevalence. 1,341 treated participants were followed up at, 1, 2 and 3 months and 382 untreated (ineligible) participants at 3 and 6 months after baseline. Headlice diagnosis was determined by examination of the scalp. Logistic regression was used to identify risk factors for headlice at baseline, and to estimate the treatment effect at each time point. This study is registered with ClinicalTrials.gov (NCT04966702).
Results
The baseline prevalence of headlice was 11%. Risk factors included living with a household member with head itch, being female, and living with poor water and sanitation facilities. The treated population receiving ivermectin had significantly lower odds of having headlice at 3 months compared to those receiving albendazole (aOR 0.22 95%CI 0.05–0.89). There was no indirect effect on headlice among ineligible children.
Conclusion
In a highly endemic setting, mass drug administration with ivermectin significantly reduces headlice infestation prevalence among those who receive the drug for three sequential months. The lack of effect among untreated, ineligible children implies that additional interventions would be needed to interrupt local transmission.
The instructor and students mentoring program: interference towards a complete student academic performance in Queen College in Human Resource Management class
Authors: Alehegn Derese 
Published: October 2024

Abstract

This study looks into how a mentorship programmer can improve a student's academic achievement in a classroom. In order to evaluate the efficacy of the programmed, the study uses a mixed-methodology approach that includes qualitative data collection techniques. The intervention entails students receiving mentorship from an experienced instructor with the goal of enhancing both academic performance and student confidence. The study's conclusions point to a beneficial impact on academic performance because programmed participants' academic outcomes significantly improved. Additionally, the mentoring program was effective in raising students' self-assurance when it came to presenting their work. A consistent method of tracking and evaluating student development was weekly formative attendance follow-up, which provided a trustworthy gauge of the intervention's success.
Effects of open-label placebos across outcomes and populations: An updated systematic review and meta-analysis of randomized controlled trials
Authors: Fendel Johannes C. , Tiersch Carl , Sölder Paul , Gaab Jens , Schmidt Stefan 
Published: October 2024

Abstract

This work synthesizes and updates findings from four previous systematic-reviews and meta-analyses on open-label placebos (OLPs). For the first time, it directly tests whether OLPs have different effects on self-report versus objective outcomes and on clinical versus non-clinical samples. We searched eight data-bases up to November 9, 2023, and included 58 randomized controlled trials (RCTs), compromising 61 separate comparisons. OLPs yielded a small positive effect across various health-related conditions (k = 61, n = 4569, SMD = 0.36, 95% CI = 0.26; 0.45, p < 0.0001; I² = 56%). The OLP effect differed between self-report outcomes (k = 55, n = 3171, SMD = 0.40) and objective outcomes (k = 14, n = 1176, SMD = 0.02, Q = 9.81, p < 0.01), and between clinical samples (k = 22, n = 1398, SMD = 0.48) and non-clinical samples (k = 39, n = 3,171, SMD = 0.29, Q = 4.69, p < 0.05). Neithter the level of suggestiveness nor the type of control moderated the effect. These findings confirm on a large dataset that OLPs are effective for self-report but not for objective outcomes. They also point to potential differences in effectiveness and mechanisms in comparsion to deceptive placebos.
CENP-A promotes cervical cancer progression through p53 pathway
Authors: Wang Yulin , Chen Shuang , Zhai Yuqing , Cao Wenjing , Zhang Zongliang , Tan Xueying , Yuan Jiangshui , Song Weiqing 
Published: October 2024

Abstract

Background: Centromere protein A (CENP-A) is a variant of histone H3 found in the centromeric chromatin, it plays a crucial role in chromosome segregation. The specific mechanisms by which CENP-A regulates cervical cancer (CC) progression have not been previously elucidated.
Methods: The Cancer Genome Atlas (TCGA) and Gene-Expression Omnibus（GEO）were used to analyze CENP-Aexpression in CC. Gene set enrichment analysis was constructed through GSEA. The expression of CENP-A in CC were tested using immunohistochemistry (IHC) staining. CC cells were transfected with LV- CENP-A-RNAi vector to decrease the CENP-A expression. Cell phenotype assays were used to detect the survival, proliferation and migration of cells. The cell apoptosis of CC cells was analyzed by flow cytometry assays.
Result: The expression of CENP-A was higher in cervical cancer tissues and cells compared with that in the adjacent paracancerous tissues. Gene enrichment analysis showed that the genes closely related to CENP-A were mainly related to the cell cycle, oocyte meiosis, pyrimidine metabolism, and the p53 signaling pathway in biological processes. The downregulation of CENP-A resulted in a reduction in the proliferation and migration of CC cells and an increase in cell apoptosis in vitro. In addition, p53, BAX and caspase3 were increased, whereas the expression of Bcl2 was decreased in the CENP-A-downregulated CC cells. After treatment with an antagonist of p53 (Pifithrin-α), the phenotype of CC cells proliferation inhibition was recovered.
Conclusion: CENP-A overexpression may be regulated to poor prognosis in patients with cervical cancer. These results suggest that CENP-A may associated with cell apoptosis and proliferation in cervical cancer cells and this may be mediated by p53 signal pathway. CENP-A may be used as a predictor of diagnosis,progression and prognosis in patients with cervical cancer.
Genetic Evidence Supports the Therapeutic Potential of Immune Checkpoint PD-L2 in the Development of Keloid
Authors: Wang Ben , Deng Yiwen , Ran Zhujie , Pan Bo , Jiang Haiyue 
Published: October 2024

Abstract

Keloids are pathological scars that extend beyond the original skin injury, resembling tumor-like growth, with unclear etiology and challenging treatment. This study aims to determine whether there is a causal link between the immune checkpoint PD-L2 and keloid risk, assessing immune checkpoints as potential therapeutic targets. A Mendelian randomization analysis was conducted using genome-wide association study summary statistics. PD-L2 expression levels were analyzed in Asian and European cohorts to explore their association with keloid risk. Two clinical cohorts with different ancestries were used to investigate association between PD-L2 expression and the risk of keloids. The Asian cohort included 178,726 samples (1055 cases), while the European cohort included 481,912 samples (668 cases). Our findings indicate that higher levels of PD-L2 expression in plasma proteome are associated with an increased risk of keloids. This conclusion holds true in both European and Asian large-scale cohorts, with OR (Asia) values of 1.25 (1.04-1.51), P_IVW=0.02, and OR (Europe) of 1.24 (1.07-1.43), P_IVW=0.004. This study reveals for the first time a causal relationship between the expression levels of the immune checkpoint PD-L2 and the risk of keloids. This provides a new perspective for understanding the pathogenesis of keloid and for developing new treatment and prevention strategies.
GPC2 provides prognostic value in pan-pediatric cancers and is associated with MYCN amplification in neuroblastoma：Bioinformatics Analysis and Validation
Authors: Xu Yanfeng , Zhou Ziang , Dong Yanqun , Wang Guanyun , Zheng Lingling , Lu Xia , Li Siqi , Zhang Mingyu , Gong Jianhua , Yang Jigang 
Published: October 2024

Abstract

Background
Glypican-2 (GPC2), a member of the GPC gene family, primarily functions in developing neural and thyroid cancer tissues, exerting influence on protein transduction, cellular proliferation and differentiation, as well as oncogenic signatures. GPC2 exhibits significant overexpression in the majority of neuroblastoma (NB) samples while remaining nearly undetectable in normal pediatric tissue samples.
Methods
Overall survival (OS) was employed as a key parameter to investigate the correlation between GPC2 expression and pan-pediatric cancers. To assess the association between GPC2 expression and clinical parameters of NB, box plots followed by t-tests were utilized. Protein-protein interaction (PPI) networks and gene-gene interaction networks were constructed. Functional roles were determined through Ontology (GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The XCell was employed to analyze the relationship between GPC2 expression and immune-related cells. Additionally, we retrospectively collected clinical data and survival information from a cohort of 51 patients diagnosed with NB and conducted immunohistochemistry (IHC) on the specimens as a validation set.
Results
Except for osteosarcoma, high expression of GPC2 was significantly associated with lower survival rates in the remaining six pediatric tumors, particularly NB and brain tumors. Notably, the MYCN amplified group exhibited significantly higher levels of GPC2 expression. Furthermore, GPC2 expression showed a positive correlation with infiltrating basophils, CD4 T cells, CD8 T cells, CD8 naïve T cells, Tgd cells, Th1 cells, Th2 cells and pro B cells, while demonstrating a negative correlation with infiltrating fibroblasts, macrophages M1 and M2 subtypes, monocytes neutrophils and pDCs. Among all 51 pediatric NB patients analyzed in this study, the MYCN amplified group displayed significantly higher levels of GPC2 expression compared to the MYCN not-amplified group. Additionally, survival analysis revealed that individuals with high GPC2 expression had significantly worse OS compared to those with low expression (P = 0.018).
Conclusion
A significant correlation was observed between elevated GPC2 expression and reduced survival rates in six pediatric tumors, particularly in cases of NB and brain tumors. Furthermore, the expression level of GPC2 in NB showed a positive association with MYCN status and levels of immune cell infiltration.
Interplay between antipredator behavior, parasitism, and gut microbiome in wild stickleback populations
Authors: Varg Javier Edo , Brealey Jaelle C. , Benhaïm David , Losada-Germain Rafael , Boughman Janette W. 
Published: October 2024

Abstract

Background
The role of predation stress in driving behavioral and microbial-host interaction changes is recognized, but the impact of microbial composition in aquatic organisms and its relationship with stress-related behavior remains poorly understood. This study explored the relationship between antipredator behavior, parasitism, and the gut microbiome in wild stickleback fish populations from two different lakes: Galtaból, clear and spring-fed versus Þristikla, turbid and glacial-fed. We aimed to identify potential links between these factors by analyzing behavioral responses to simulated predation, comparing microbiomes between populations with or without parasite infection, and examining potential correlations between behavior and microbiome composition.
Results
Behavioral analysis revealed differences between populations, with each exhibiting unique baseline behaviors i.e., higher activity in Galtaból fish and higher angular velocity in Þristikla fish, and varied responses to the presence of predator i.e., increased boldness in Galtaból fish and higher activity in Þristikla fish. The response to the predator attack was similar between fish from both populations. Parasitism influenced behavior, with parasitized fish displaying increased boldness. Microbiome analysis showed that a small proportion of its variation was explained by population, likely reflecting differences in lake environments. Only the marine genus Pseudoalteromonas abundance differed between populations. Parasitism in Galtaból fish population was linked to decreased alpha diversity in the microbiome, with an increase in specific microbial taxa, including potential pathogens, and a decrease in commensal microbes.
Conclusions
Our findings suggest that behavior and microbiome correlations may primarily reflect environmental adaptations and parasite status rather than direct gut-brain interactions. However, some tentative evidence suggests a potential innate connection between swimming activity, stress levels, and specific microbes. The study highlights the complexity of the gut-brain axis in wild populations and suggests future research directions, including experimental manipulations to uncover causal relationships between microbiome composition and behavior.
Pheromone release and perception, and fertility of insecticide-exposed cotton boll weevils (Anthonomus grandis grandis)
Authors: Omari Sharrine , Marra¹ D. Oliveira , Laumann Raul A. , Blassioli-Moraes Maria Carolina , Guedes Raul Narciso C. , Borges Miguel , Barbosa Wagner F. , Ferreira Marinaldo loures , Zanine Anderson M. , Batista Paulo S. C. 
Published: October 2024

Abstract

The objective of this work was to evaluate the effects of sublethal exposure to the insecticides malathion and beta-cyfluthrin on the pheromone perception and emission by the cotton boll weevil (Anthonomus grandis grandis Boheman (Coleoptera: Curculionidae)). The potential impact of such sublethal exposure on this species population growth was also determined using fertility table parameters. Males and females were exposed to malathion at 10% of the label rate for 1 min, and to beta-cyfluthrin either at the full or 20% label rate also for 1 min. The response of insects exposed and non-exposed to pesticides to their aggregation pheromone (grandlure) was evaluated in Y-tube olfactometer and the pheromone production was evaluated. In order to evaluate the possible reproductive effects, the couples remained individualized for 48 hours and the females were subsequently evaluated until their death. The treatments were: 1) insecticide-exposed male and female; 2) exposed male; 3) exposed female; and 4) non-exposed males and females. Insects exposed to both insecticides did not show a response to their aggregation pheromone during the first 24 hours after the exposition. However, insecticide-exposed males did not have their pheromone production affected compared to non-exposed males. Sublethal insecticide exposure compromised the net reproductive rate (Ro) compromising the intrinsic rate of population growth (rm) of the cotton boll weevil.