title: PeerJ description: Articles published in PeerJ link: https://peerj.com/articles/index.rss3?journal=peerj&page=129 creator: info@peerj.com PeerJ errorsTo: info@peerj.com PeerJ language: en title: Comparison of 1-year mortality predictions from vendor-supplied versus academic model for cancer patients link: https://peerj.com/articles/18958 last-modified: 2025-02-11 description: PurposeThe Epic End of Life Care Index (EOLCI) predicts 1-year mortality for a general adult population using medical record data. It is deployed at various medical centers, but we are not aware of an independent validation. We evaluated its performance for predicting 1-year mortality in patients with metastatic cancer, comparing it against an academic machine learning model designed for cancer patients. We focused on this patient population because of their high short-term mortality risk and because we had access to the comparator model predictions.Materials and MethodsThis retrospective analysis included adult outpatients with metastatic cancer from four outpatient sites. Performance metrics included AUC for 1-year mortality and positive predictive value of high-risk score.ResultsThere were 1,399 patients included. Median age at first EOLCI prediction was 67 and 55% were female. A total of 1,283 patients were evaluable for 1-year mortality; of these, 297 (23%) died within 1 year. AUC for 1-year mortality for EOLCI and academic model was 0.73 (95% CI [0.70–0.76]) and 0.82 (95% CI [0.80–0.85]), respectively. Positive predictive value was 0.38 and 0.65, respectively.ConclusionThe EOLCI’s discrimination performance was lower than the vendor-stated value (AUC of 0.86) and the academic model’s performance. Vendor-supplied machine learning models should be independently validated, particularly in specialized patient populations, to ensure accuracy and reliability. creator: Michael F. Gensheimer creator: Jonathan Lu creator: Kavitha Ramchandran uri: https://doi.org/10.7717/peerj.18958 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2025 Gensheimer et al. title: Efficacy of sacubitril/valsartan on improving clinical symptoms in patients with acute myocardial infarction complicated with heart failure: a retrospective study link: https://peerj.com/articles/18873 last-modified: 2025-02-11 description: BackgroundAcute myocardial infarction (AMI) significantly contributes to the progression of heart failure (HF). Standard treatment for HF has long been angiotensin-converting enzyme inhibitors (ACEIs), targeting the renin-angiotensin-aldosterone system (RAAS). Recent developments in HF management introduced sacubitril/valsartan (S/V), a novel angiotensin receptor-neprilysin inhibitor (ARNI), showing promising results in global trials. This study aimed to assess the efficacy of early S/V application compared to angiotensin-converting enzyme inhibitors (ACEIs) in reducing NT-proBNP levels and improving clinical outcomes, specifically focusing on dyspnea symptomatology, in Chinese patients with AMI complicated by HF.MethodsThis single-center, mixed methods study was conducted at Tangshan Gongren Hospital from January to December 2021, including 88 patients diagnosed with AMI and HF. Patients were divided into two groups: 31 received S/V, while 57 were treated with ACEIs. Data collection encompassed baseline demographic, clinical, and biochemical variables, NT-proBNP levels, blood pressure measurements, and dyspnea symptom severity. Follow-up assessments were conducted 1 year post-discharge to evaluate NT-proBNP levels, and symptom progression. Statistical analyses, including t-tests, Wilcoxon rank-sum tests, and chi-square tests, were performed to compare outcomes between the two groups.ResultsAt baseline, no significant differences were observed between the two groups in terms of demographic, lifestyle, and medical history. Although patients in the S/V group presented with more severe baseline renal impairment and cardiac dysfunction, there was no significant difference in NT-proBNP levels from admission to discharge. 1-year follow-up showed a trend towards reduced NT-proBNP levels in the S/V group, though this difference did not reach statistical significance. All patients in both groups reported improvements in dyspnea at discharge and at follow-up, with no significant inter-group difference. Notably, the S/V group demonstrated a more significant reduction in both systolic and diastolic blood pressure from admission to discharge compared to the ACEIs group.ConclusionsThis study found that S/V had similar effects to ACEIs in reducing NT-proBNP levels among Chinese patients with AMI complicated by HF, though S/V was associated with greater reductions in blood pressure. These findings suggest that while S/V may offer additional benefits in blood pressure management, its impact on cardiac biomarkers in acute settings may not significantly differ from ACEIs. Given the study’s limitations, including its single-center design, small sample size, and baseline differences. Further multi-center, randomized controlled trials are warranted to validate these findings and explore tailored treatment strategies for AMI patients with concurrent HF. creator: Guiping Wang creator: Ruolin Zhang creator: Xuyang Li creator: Shuping Zuo creator: Boheng Zhang creator: Yanan Zhao creator: Suya Sun creator: Juanjuan Zhang creator: Xiaokun Liu uri: https://doi.org/10.7717/peerj.18873 license: https://creativecommons.org/licenses/by-nc/4.0 rights: © 2025 Wang et al. title: Modelling asynchrony in phenology considering a dynamic representation of meteorological variables link: https://peerj.com/articles/18653 last-modified: 2025-02-11 description: Shifts in the timing of phenological events across many taxa and ecosystems are a result of climate change. Within a trophic network, phenological mismatches between interlinked species can have negative impacts for biodiversity, ecosystems, and the trophic network. Here we developed interaction indices that quantify the level of synchrony and asynchrony among groups of species in three interlinked trophic levels, as well as accounting for a dynamic representation of meteorology. Insect first flight, vegetation green-up and arrival of migrant birds were the phenological indicators, obtained from a combination of spatially and temporally explicit species observations from citizen science programmes and remote sensing platforms (i.e., Landsat). To determine phenological shifts in interlinked taxa we created and applied several phenological indices of synchrony-asynchrony, combining information from the phenological events and critical time windows of meteorological variables. To demonstrate our method of incorporating a meteorological component in our new interaction index, we implemented the relative sliding time window analysis, a stepwise regression model, to identify critical time windows preceding the phenological events on a yearly basis. The new indices of phenological change identified several asynchronies within trophic levels, allowing exploration of potential interactions based on synchrony among interlinked species. Our novel index of synchrony-asynchrony including a meteorological dimension could be highly informative and should open new pathways for studying synchrony among species and interaction networks. creator: Rubén de la Torre Cerro creator: Gourav Misra creator: Emily Gleeson creator: Guy Serbin creator: Jesko Zimmermann creator: Fiona Cawkwell creator: Astrid Wingler creator: Paul Holloway uri: https://doi.org/10.7717/peerj.18653 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2025 de la Torre Cerro et al. title: N. sphaeroides phycocyanin subunit Ns-α and Ns-β improve C. elegans antioxidative capacity via ROS-related regulation link: https://peerj.com/articles/18917 last-modified: 2025-02-10 description: Oxidative stress and damage to macromolecules due to free radicals such as reactive oxygen species (ROS) are commonly considered factors that can impair health. This study investigated the potential antioxidant properties of of two subunit proteins associated with the pigment-protein complex phycocyanin derived from Nostoc sphaeroides (Gexianmi). Bacterial expression vectors were separately constructed to induce the two engineering subunit proteins, Ns-α and Ns-β. These engineering proteins were then examined for their potential to enhance antioxidative capacity in Caenorhabditis elegans. Firstly, a proper concentration of the proteins Ns-α and Ns-β in vitro exhibited 2, 2-azino-bis 3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging activity. Secondly, while there were no other observed effects on the nematodes, those treated with the proteins showed significant improvements in motility and reduced levels of lipofuscin compared to the control group. Furthermore, thirdly, the treated nematodes demonstrated increased resistance to oxidation, as evidenced by the higher survivals under oxidative conditions induced by 5 mM H2O2. Notably, the treated nematodes exhibited decline in endogenous ROS levels, and the redox-related genes, such as SOD-3 and CAT-1, were down-regulated following consumption of the engineering proteins. Taken together, these findings suggest that engineering proteins Ns-α and Ns-β improve the antioxidative capacity of C. elegans by modulating ROS-related regulation, making them potential modulators in responding to oxidative stressors. creator: Xiaoyu Wu creator: Caiyun Zhang creator: Shuwen Zhou creator: Chao Cheng creator: Qing Fang uri: https://doi.org/10.7717/peerj.18917 license: https://creativecommons.org/licenses/by-nc/4.0 rights: © 2025 Wu et al. title: Enhancing active ingredient biosynthesis in Chinese herbal medicine: biotechnological strategies and molecular mechanisms link: https://peerj.com/articles/18914 last-modified: 2025-02-10 description: BackgroundChinese herbal medicine (CHM) is a fundamental component of traditional Chinese medical practice, offering a rich source of natural remedies with significant therapeutic potential. However, the scarcity of active ingredients and complex extraction procedures present substantial challenges to their widespread clinical application. This review aims to address this gap by exploring the potential of modern biotechnological advancements in enhancing the biosynthesis of these valuable compounds.MethodologyThe study takes a comprehensive approach, delving into the chemical composition of CHM’s active ingredients and elucidating their biosynthetic pathways and molecular regulatory mechanisms. Additionally, it surveys recent progress in extraction methodologies and evaluates engineering strategies aimed at synthetic production. This multifaceted analysis forms the foundation for examining the role of synthetic biology in augmenting CHM’s active ingredient synthesis.ResultsOur examination provides insights into the intricate biosynthetic pathways governing the formation of CHM’s active ingredients, as well as the complex molecular regulatory networks that underlie these processes. Furthermore, the review highlights advancements in extraction techniques, demonstrating their ability to streamline and enhance the isolation of these compounds. Engineering approaches for synthetic production, including metabolic engineering and synthetic biology tools, are assessed for their potential to overcome natural limitations and scale up production.ConclusionsBy integrating insights from biosynthesis, molecular regulation, extraction methodologies, and synthetic biology, this review establishes a robust theoretical framework for enhancing the production of CHM’s active ingredients. The proposed strategies and practical guidance aim to facilitate their broader utilization in modern medicine while promoting sustainability and accessibility within this invaluable medicinal heritage. creator: Ziyi Guo creator: Ning Yang creator: Delin Xu uri: https://doi.org/10.7717/peerj.18914 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2025 Guo et al. title: A gene signature related to programmed cell death to predict immunotherapy response and prognosis in colon adenocarcinoma link: https://peerj.com/articles/18895 last-modified: 2025-02-10 description: BackgroundTumor development involves the critical role of programmed cell death (PCD), but the correlation between colon adenocarcinoma (COAD) and PCD-related genes is not clear.MethodsSubtyping analysis of COAD was performed by consensus clustering based on The Cancer Genome Atlas (TCGA), with the AC-ICAM queue from the cBioportal database as a validation set. Immune infiltration of the samples was evaluated using CIBERSORT and Microenvironment Cell Populations (MCP)-counter algorithms. Patients’ immunotherapy response was predicted by the TIDE and aneuploidy scores. Pathway enrichment analysis was conducted with gene set enrichment analysis (GSEA). A RiskScore model was established with independent prognostic PCD-related genes filtered by Cox regression analysis. The mafCompare function was used to compare the differences in mutation rates of somatic genes. Wound healing, transwell assays and Flow cytometer were applied to measure the cell migration, invasion and apoptosis.ResultsThe patients were grouped into S1 and S2 subtypes based on a total of 21 PCD genes associated with the prognostic outcomes of COAD. Specifically, patients of S1 subtype were mainly related to the pathway activation in tumor invasion and deterioration and had a worse prognosis. A RiskScore model was established based on six prognostic genes, including two protective genes (ATOH1, ZG16) and four risk genes (HSPA1A, SEMA4C, CDKN2A, ARHGAP4). Notably, silencing of CDKN2A inhibited the activity of migration and invasion and promoted apoptosis of tumor cells. Based on the RiskScore model, the patients were grouped into high- and low-risk groups. Independent prognostic factors, namely, Age, pathologic_M, pathologic_stage, and RiskScore, were integrated to develop a nomogram with strong good prediction performance. High-risk group had high-expressed immune checkpoint genes and higher TIDE scores, showing a strong immune escape ability and less active immunotherapy response. Compared to the low-risk group, TP53 exhibited a higher rate of somatic mutation in the high-risk group.ConclusionWe constructed a RiskScore model with six PCD-related genes for the prognostic assessment of COAD, providing a valuable insight into the exploration of new targets for the prognostic improvement in COAD. creator: Lei Zheng creator: Jia Lu creator: Dalu Kong creator: Yang Zhan uri: https://doi.org/10.7717/peerj.18895 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2025 Zheng et al. title: Microplastic effects on mouse colon in normal and colitis conditions: A literature review link: https://peerj.com/articles/18880 last-modified: 2025-02-10 description: BackgroundTaking into account the global spread of microplastic (MP) pollution, the problem of the MP impact on human health is relevant. MP enters the organism predominantly with water and food, and is mostly detected in the large intestine. Therefore, the connection between MP pollution and the increase in colitis is an important question. In order to assess the toxic and pathogenetic effects of MP, experimental studies were actively conducted during recent years, mainly on laboratory mice.ObjectivesThe aim of our review was to summarize and systematize the data on the MP effect on mice colon under normal conditions and during colitis in order to assess the role of MP in the development of intestinal diseases. This manuscript could be relevant for ecologists, experimental biologists, and physicians dealing with problems related to anthropogenic environmental changes and inflammatory bowel diseases.Survey MethodologyThe search was conducted based on PubMed data about original experimental studies of the MP effects on the colon of healthy mice and mice with colitis.ResultsIn healthy mice colon, MP can cause oxidative stress, increased permeability, immune cell infiltration, production of proinflammatory factors, and decreased mucus production. MP affects proliferation, apoptosis, and differentiation of epithelial cells, expression of tight junction components and glycocalyx, membrane transport, signaling pathways, metabolome, and intestinal microflora composition. In mice with acute and chronic experimental colitis, MP consumption leads to a more pronounced pathological process course.ConclusionsMP may be one of the factors contributing to the development of colitis in humans. However, further research is needed. creator: Natalia Zolotova creator: Dzhuliia Dzhalilova creator: Ivan Tsvetkov creator: Maria Silina creator: Nikolai Fokichev creator: Olga Makarova uri: https://doi.org/10.7717/peerj.18880 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2025 Zolotova et al. title: Nanoparticles modified bioceramic sealers on solubility, antimicrobial efficacy, pushout bond strength and marginal adaptation at apical-third of canal dentin link: https://peerj.com/articles/18840 last-modified: 2025-02-10 description: ObjectiveThe present study investigates the solubility, antimicrobial potency, pushout bond strength (PBS), and marginal adaptation of sealer modified using various nanoparticles (NPs) (silver, chitosan, HapNPs) to the root dentin at the apical third.MethodsForty-four human premolars were prepared for root canal treatment via a chemical mechanical approach. The teeth included were subsequently distributed into four groups based on the type of modified and unmodified sealers. Group 1 bioceramic (BC) sealer (Control), Group 2 (AgNPs modified BC sealer), Group 3 (CHNPs modified BC sealer), and Group 4 (HApNPs modified BC sealer). Solubility was assessed by making five samples and measured via precision balance. Antimicrobial testing against E. faecalis was performed using the Agar diffusion test. The bond strength and failure modes were assessed utilizing a universal testing machine and stereomicroscope respectively. A pair of specimens from each cohort was fixed to an aluminum stub to assess marginal adaptation via SEM at the apical third. Data analysis was performed utilizing one way ANOVA and followed by Tukey’s post hoc test (p < 0.05).ResultsSealers-modified HApNPs exhibited the lowest solubility (3.884 ± 0.15%) and strongest PBS (9.63 ± 0.12 MPa). Group 1 (Control) demonstrated highest solubility rate (6.144 ± 0.39%) and weakest bond strength (6.50 ± 0.09 MPa). All the modified sealers exhibited the largest zone of inhibition with no significant difference. Whereas the unmodified BC sealer group presented the smallest zone of bacterial inhibition.ConclusionMarginal adaptation of sealers does not affect the bond strength outcomes achieved. The incorporation of silver, chitosan, and hydroxyapatite nanoparticles into BC root canal sealers resulted in reduced solubility, enhanced antibacterial efficacy, and improved PBS compared to unmodified BC canal sealers. creator: Basil Almutairi creator: Fahad Alkhudhairy uri: https://doi.org/10.7717/peerj.18840 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2025 Almutairi and Alkhudhairy title: The association between serum lipids at diagnosis and renal outcome in microscopic polyangiitis patients link: https://peerj.com/articles/18839 last-modified: 2025-02-10 description: ObjectivesMicroscopic polyangiitis (MPA) is a subgroup of ANCA-associated vasculitis (AAV), which is characterized by vascular endothelial cell damage caused by abnormally activated neutrophils. Dyslipidemia is associated with vascular endothelial cell injury, and the relationship between blood lipid levels and renal prognosis in MPA patients is not clear. We aim to investigate the correlation between blood lipid levels at diagnosis and renal prognosis in MPA patients.MethodsFirstly, we retrospectively included 110 patients diagnosed with MPA and the primary endpoint was the occurrence of end stage renal disease (ESRD). The association between blood lipids at diagnosis and renal outcome was evaluated with Cox regression analysis and survival analysis. Secondly, we explored the potential underlying mechanism of poor renal prognosis in patients with high triglycerides (TG) levels at diagnosis using data independent acquisition (DIA) quantitative proteomics.ResultsDuring a median follow-up period of 23 months, 44 out of 110 patients (40%) developed ESRD. High serum TG at diagnosis was associated with ESRD development after adjusting for several confounding factors including age, gender, body mass index (BMI), hypertension, diabetes mellitus, estimated glomerular filtration rate (eGFR) and Birmingham Vasculitis Activity Score (BVAS). Serum very low-density lipoprotein (VLDL) demonstrated a marginal trend towards association with ESRD development. MPA patients with TG >1.45 mmol/L or VLDL > 0.66 mmol/L had significantly higher risk of ESRD development than those with TG ≤ 1.45 mmol/L or VLDL ≤ 0.66 mmol/L. DIA quantitative proteomics analysis suggested that patients with elevated TG levels and severe MPA had an upregulation of profibrotic pathways, inflammatory signaling, and complement and coagulation cascades, in contrast to those with lower TG levels and milder disease severity.ConclusionsIn MPA patients, high TG or VLDL at diagnosis is associated with an increased risk of ESRD development. The potential mechanisms may be associated with the upregulation of profibrotic and inflammatory signaling pathways, and the activation of complement and coagulation cascades. creator: Zigui Zheng creator: Yujia Wang creator: Jingzhi Xie creator: Zhimin Chen creator: Bingjing Jiang creator: Yanfang Xu uri: https://doi.org/10.7717/peerj.18839 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2025 Zheng et al. title: Genome-wide survey and expression analysis of the OMT gene family in Stephania japonica link: https://peerj.com/articles/18600 last-modified: 2025-02-10 description: BackgroundO-methyltransferase (OMT) is an important rate-limiting enzyme that plays a vital role in synthesizing various key metabolites, such as benzylisoquinoline alkaloids (BIA). Nevertheless, there is a dearth of extensive research on the analysis of the OMT gene family in Stephania japonica, a main source of cepharanthine with an anti-coronavirus effect.MethodsTwo OMT family genes, SjCCoAOMT and SjCOMT, were identified from the high-quality genome of S. japonica during this investigation. Further analysis of SjCCoAOMT and SjCOMT genes involved chromosome distribution, gene structure, phylogenetic relationship, conserved motif, expression profile, quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) experiments an d cis-acting elements analysis.ResultsThere are six SjCCoAOMT members and fifty-two SjCOMT members in the genome of S. japonica, which are unevenly distributed on 11 chromosomes. OMTs could be clustered into SjCCoAOMT and SjCOMT subfamilies through phylogenetic relationship, consistent with the conserved motif and gene structure analysis results. The expression profile revealed SjCOMT11 and SjCOMT13 showed specific expression levels mainly in root. SjCOMT21, SjCOMT33 and SjCOMT37 were significantly expressed in the root and slightly expressed in the stem, bud and leaf. SjCOMT15 and SjCOMT45 were not only significantly expressed in root, but also expressed highly in leaf. Significantly enhanced expression of SjCOMT11, SjCOMT13, SjCOMT15, SjCOMT21, SjCOMT33, SjCOMT37, and SjCOMT45 suggested these OMTs are essential for cepharanthine synthesis in the S. japonica roots. Cis-acting element analysis revealed the potential roles of OMTs in S. japonica in growth, development, and resistance to stress. These findings provide insight into understanding the functions and characterization of OMTs from S. japonica and lay a foundation for further revealing the role of the OMT genes in the biosynthesis of cepharanthine. creator: Zenghao Bi creator: Tianxing He creator: Yuting Liang creator: Changqing Zhou creator: Yuetong Yu creator: Liang Leng uri: https://doi.org/10.7717/peerj.18600 license: https://creativecommons.org/licenses/by-nc/4.0 rights: © 2025 Bi et al.