title: PeerJ
description:  Articles published in PeerJ
link: https://peerj.com/articles/index.rss3?journal=peerj&page=39
creator: info@peerj.com PeerJ
errorsTo: info@peerj.com PeerJ
language: en

title: Mendelian randomization and nomogram-based prediction of hepatocellular carcinoma risk in patients with hepatitis B cirrhosis
link: https://peerj.com/articles/20179
last-modified: 2025-10-20
description: BackgroundTo innovatively integrate genetic causality and multidimensional clinical indicators, we aimed to investigate causal relationships between metabolic-inflammatory biomarkers and hepatocellular carcinoma (HCC) risk in hepatitis B-related cirrhosis (HBV-C) using Mendelian randomization (MR), and develop a precision prediction model combining genetic evidence with nonlinear biochemical dynamics.MethodsLeveraging bidirectional approaches, we first performed two-sample MR analysis on GWAS datasets (UK Biobank, n = 456,348) to establish causality between low-density lipoprotein (LDL) and HCC. In a retrospective cohort of patients with HBV-related cirrhosis from our institution (n = 147; 2022–2024), we identified nonlinear LDL-HCC thresholds via restricted cubic splines (RCS) and engineered a novel “A-index” (a composite score derived from principal component analysis (PCA) integrating alpha-fetoprotein (AFP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT)). Machine learning-driven logistic regression synthesized LDL, A-index, and clinical predictors into a nomogram, rigorously validated by area under the curve-receiver operating characteristic (AUC-ROC), calibration curves, and decision curve analysis (DCA).ResultsMR analysis revealed a robust causal link between reduced LDL levels and elevated HCC risk (OR = 0.472, 95% CI [0.259–0.860]; P = 0.014), with RCS identifying a critical LDL threshold at 2.28 mmol/L—below which HCC risk escalated exponentially. The PCA-synthesized A-index outperformed individual biomarkers (AUC = 0.652 vs. AFP = 0.579). The final nomogram integrating LDL dynamics, A-index, age, sex, prothrombin time, and antiviral therapy achieved exceptional discrimination (AUC = 0.938) and clinical net benefit across risk thresholds.ConclusionThis study introduces a novel causal inference-guided prediction model, addressing the long-standing debate on LDL’s dual role in hepatocarcinogenesis. By integrating MR-validated genetic causality, nonlinear biochemical modeling, and PCA-driven dimensionality reduction, our model provides a transformative tool for personalized HCC risk stratification in HBV-C patients.
creator: Xiaolong Zheng
creator: Yiping Hong
creator: Wei Wei
uri: https://doi.org/10.7717/peerj.20179
license: https://creativecommons.org/licenses/by/4.0/
rights: ©2025 Zheng et al.

title: Easier said than done: unexpected hurdles to preparing ∼1,000 cranial CT scans for data collection from an online digital repository
link: https://peerj.com/articles/20172
last-modified: 2025-10-20
description: BackgroundAs science becomes more open and accessible, researchers are increasingly encouraged—and sometimes required—to share their digital data on public repositories. While this promotes transparency and reusability, it can also introduce challenges. We highlight one such challenge by detailing our experience processing computerized tomography (CT) scans of 985 baboon skulls downloaded from MorphoSource, part of a quantitative genetic study of craniodental variation in the pedigreed baboon colony from the Southwest National Primate Research Center. When importing DICOM files into 3D Slicer, 182 of the 985 scans (18.5%) generated an “inconsistent slice spacing” error. When prompted, 3D Slicer “corrected” this by regularizing the slice spacing. However, this led to a mismatch between the slice spacing reported on MorphoSource and the spacing adjusted by 3D Slicer.MethodsTo determine which slice spacing was accurate, we compared Prosthion-Basion (PR-BA) distances measured directly from physical skulls (using calipers and a Microscribe) with those derived from the CT models. We ran paired t-tests to determine whether there were differences between them. Our comparison sample included five randomly selected skulls from the error group and fifteen ramdon skulls from the error-free group (which exhibited various slice spacings when scanned).ResultsFor scans without the slice spacing error, there was strong agreement between physical and digital measurements, indicating metadata accuracy. For error-generating scans, measurements based on 3D Slicer’s corrected spacing and Amira-Avizo both aligned well with the physical data. In contrast, manually overriding the spacing to match the MorphoSource metadata led to overestimations of the PR-BA distance.ConclusionAlthough the discrepancy was straightforward to describe, resolving it required over 250 person-hours across 8 months. Accessing physical specimens, conducting repeated measurements, and cross-validating with multiple tools made the process labor-intensive. Nonetheless, this effort avoided a 3–5% measurement bias in nearly 20% of our sample and allowed inclusion of these scans in downstream semi-automated data collection. We urge researchers to thoroughly understand the digital datasets they work with and resist the temptation to ignore apparent errors during import. We also recommend that funding bodies provide support for the extensive time needed to validate and process digital imagery, both for data generators and users. Finally, we highlight the need for public repositories to implement stronger quality control. If a data import check similar to 3D Slicer’s had been applied during data submission, the inconsistency between manually entered metadata and embedded DICOM information might have been caught and corrected at the time of upload.
creator: Mario Modesto-Mata
creator: Arthur Thiebaut
creator: Kristin L. Krueger
creator: A. Murat Maga
creator: Jessica L. Joganic
creator: Timothy M. Ryan
creator: Joan T. Richtsmeier
creator: James M. Cheverud
creator: Leslea J. Hlusko
uri: https://doi.org/10.7717/peerj.20172
license: https://creativecommons.org/licenses/by/4.0/
rights: ©2025 Modesto-Mata et al.

title: Effects of low-level electric current on the growth of Amphistegina lobifera and its photosynthetic diatom endosymbionts
link: https://peerj.com/articles/20160
last-modified: 2025-10-20
description: Larger benthic foraminifera (LBF) are key carbonate producers and significantly contribute to carbonate reef sediments. As the ongoing climate change threatens the calcification capacity of many marine organisms, novel approaches are being explored to support reef resilience. Among these, low-voltage electric stimulation has shown promise in enhancing calcification in corals and other marine calcifiers by stimulating electrodeposition of calcium carbonate. However, the potential of this technique to support calcification in LBF has not yet been assessed. To close this gap, the present study investigates the effects of low electric current densities on the LBF species Amphistegina lobifera. To avoid inducing mortality, the current densities were carefully selected based on previous findings and were applied in two 30-day experiments. Pulse-Amplitude Modulation (PAM) fluorometry (Fv:Fm) was used to measure the photosynthetic efficiency of the diatom endosymbionts, and total pigment content (Chl a) was analysed via a plate reader to assess pigment changes due to the electric stimulation. Growth was analysed by measuring the maximum diameter and counting the formation of new chambers labelled with the fluorogenic dye calcein. The results of both experiments show that electric stimulation did not affect the maximum quantum yield (Fv:Fm) and Chl a content. Furthermore, all treatments exhibited positive growth, but no significant growth enhancement was observed compared to the controls. The highest growth and chamber formation rate were found at current densities of 1 and 1.43 µA/cm2, which represent the highest growth rates obtained in the experiments, as an additional increase in current density to 2.86 µA/cm2 did not seem to further enhance growth. These results suggest that low electric current can influence foraminiferal growth, and the conditions necessary for a significant enhancement remain to be investigated.
creator: Federica Rebecchi
creator: Davide Lattanzi
creator: Sigal Abramovich
creator: Patrizia Ambrogini
creator: Fabrizio Frontalini
creator: Christiane Schmidt
uri: https://doi.org/10.7717/peerj.20160
license: https://creativecommons.org/licenses/by/4.0/
rights: ©2025 Rebecchi et al.

title: Serum brain-derived neurotrophic factor, micronutrient status, and inflammatory cytokines in type 2 diabetes with nephropathy: a case–control analysis
link: https://peerj.com/articles/20086
last-modified: 2025-10-20
description: BackgroundBrain-derived neurotrophic factor (BDNF) levels are lower in diabetic patients compared to healthy individuals, and may be further affected by nephropathy. This study aimed to evaluate serum BDNF levels in diabetic patients with nephropathy without complications and compare them to levels in healthy control subjects.MethodsA case–control study was conducted involving three groups: healthy individuals (controls), diabetic patients without complications (DM), and diabetic nephropathy patients (DN). Serum BDNF levels were measured using the sandwich Enzyme-Linked Immunosorbent Assay (ELISA) technique, alongside serum levels of interleukin (IL)-12, IL-16, folic acid, vitamin B12, vitamin D3, total cholesterol, triglycerides, high density lipoprotein (HDL), hemoglobin A1c (HbA1c), urea, creatinine, total calcium, and zinc.ResultsSerum BDNF levels were significantly lower in the DN group compared to the DM and control groups (42.1, 34.1, and 27.23 ng/mL, respectively). In the DM group, BDNF showed a direct correlation with HbA1c and urea (r = 0.26 and r = 0.35, respectively), and an inverse correlation with fasting plasma glucose (FPG) (r =  − 0.30). In the DN group, BDNF was directly correlated with FPG (r = 0.31) and serum creatinine (r = 0.27). The area under the curve (AUC) for BDNF in distinguishing DN from controls was 0.938, and 0.738 for DN versus DM.ConclusionSerum BDNF levels are markedly reduced in type 2 diabetic patients with nephropathy and correlate with deficiencies in vitamins D, B12, folate, and zinc, as well as elevated IL-6 and IL-12. BDNF may serve as a biomarker for diabetic kidney disease, highlighting the importance of nutritional status, inflammation control, and neurotrophic support.
creator: Huda Jaber Waheed
creator: Nawfal A. Numan
uri: https://doi.org/10.7717/peerj.20086
license: https://creativecommons.org/licenses/by/4.0/
rights: ©2025 Waheed and Numan

title: Associations of anthropometric indices with body adiposity for assessing cardiovascular risk in people living with HIV: a cross-sectional study
link: https://peerj.com/articles/18833
last-modified: 2025-10-20
description: BackgroundThe presence of HIV infection is associated with an elevated risk of developing cardiovascular disease (CVD), which can be attributed to a range of factors, related to the virus itself. These include increased levels of inflammation and immune activation. Following the introduction of antiretroviral therapy, people living with HIV (PLHIV) began to exhibit an increase in body weight. However, this was also associated with an elevated risk of developing metabolic disorders. The aim of this study was to examine the association between anthropometric indices of cardiovascular risk—waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and conicity index (CI)—with body composition and time of infection in PLHIV.MethodsAn analytical cross-sectional study consisting of 17 PLHIV of both sexes is conducted. The following anthropometric indices were measured: body weight, height, body mass index (BMI), waist and hip circumference, body fat (BF), WHR, WHtR and CI. For the purposes of statistical analysis, the agreement between the methods used for the diagnosis of cardiovascular risk was verified using the Kappa coefficient. The associations were then verified using the Pearson’s “r” coefficient. The level of significance was set at p < 0.05.ResultsThe results of the association analyzes between the anthropometric indices WHR, WHtR and CI indicated that WHR and CI were inversely correlated with total BF (kg). Consequently, there was consensus regarding CVD risk between WHR and CI, as well as between the three indices collectively. However, no significant association was observed between the anthropometric indices WHR, WHtR and CI and the duration of HIV infection.ConclusionTherefore, it can be concluded that when evaluating the risk of CVD in PLHIV, it is more reliable to associate WHR, WHtR and CI together than to use these indices separately, and total BF can be associated with CI or WHR for a risk assessment.
creator: Elaine Alana Duarte Fernandes
creator: Suerda Teixeira
creator: Phelipe Wilde De Alcântara Varela
creator: Júlio César Medeiros Alves
creator: Paulo Francisco de Almeida-Neto
creator: Carlos Gomes
creator: Breno Guilherme de Araújo Tinôco Cabral
creator: Paulo Moreira Silva Dantas
uri: https://doi.org/10.7717/peerj.18833
license: https://creativecommons.org/licenses/by/4.0/
rights: ©2025 Duarte Fernandes et al.

title: Prediction of sporulating Firmicutes from uncultured gut microbiota using SpoMAG, an ensemble learning tool
link: https://peerj.com/articles/20232
last-modified: 2025-10-17
description: Sporulation represents a key adaptive strategy among Firmicutes, facilitating bacterial persistence under environmental stress while mediating host colonization, transmission dynamics, and microbiome stability. Despite the recognized ecological and biomedical significance of spore-forming Bacilli and Clostridia, most taxa remain uncultivated, limiting phenotypic characterization of their sporulation capacity. To bridge this knowledge gap, we developed SpoMAG, an ensemble machine learning framework that predicts sporulation potential of metagenome-assembled genomes (MAGs) through supervised classification models trained on the presence/absence of 160 sporulation-associated genes. This R-based tool integrates Random Forest and support vector machine algorithms, achieving probabilistic predictions with high performance (AUC = 92.2%, F1-score = 88.2%). Application to fecal metagenomes from humans, cattle, poultry, and swine identified 63 putatively spore-forming MAGs exhibiting distinct host- and order-specific patterns. Bacilli MAGs from Bacillales and Paenibacillales orders showed high sporulation probabilities and gene richness, while Clostridia MAGs exhibited more heterogeneous profiles. Predictions included undercharacterized families in the spore-forming perspective, such as Acetivibrionaceae, Christensenellaceae, and UBA1381, expanding the known phylogenetic breadth of sporulation capacity. Nine genes were consistently present across all predicted spore-formers (namely pth, yaaT, spoIIAB, spoIIIAE, spoIIIAD, ctpB, ftsW, spoVD, and lgt), suggesting conserved genetic elements across uncultivated Firmicutes for future research. Average nucleotide identity (ANI) analysis revealed seven cases of species-level sharing (ANI value > 95%) among hosts, including a putative novel Acetivibrionaceae species, suggesting possible cross-host transmission facilitated by sporulation. In all 63 genomes predicted to sporulate, we identified nine genes across sporulation steps. In addition, SHapley Additive exPlanations (SHAP) analysis indicated 16 consensus genes consistently contributing to predictions (namely lytH, cotP, spoIIIAG, spoIIR, spoVAD, gerC, yabP, yqfD, gerD, spoVAA, gpr, ytaF, gdh, ypeB, spoVID, and ymfJ), bringing biologically meaningful features across sporulation stages. By combining gene annotation with interpretable machine learning, SpoMAG provides a reproducible and accessible framework to infer sporulation potential in uncultured microbial taxa. This tool enhances targeted investigations into microbial survival strategies and supports research in microbiome ecology, probiotic discovery, food safety, and public health surveillance. SpoMAG is freely available as an R package and expands current capabilities for functional inference in metagenomic datasets.
creator: Douglas Terra Machado
creator: Otávio José Bernardes Brustolini
creator: Ellen dos Santos Corrêa
creator: Ana Tereza Ribeiro Vasconcelos
uri: https://doi.org/10.7717/peerj.20232
license: https://creativecommons.org/licenses/by/4.0/
rights: ©2025 Terra Machado et al.

title: Accelerating silage maize breeding: forage yield and nutritive quality of doubled haploid-derived hybrids
link: https://peerj.com/articles/20197
last-modified: 2025-10-17
description: BackgroundMaize (Zea mays L.) is a widely cultivated cereal crop for silage production due to its high biomass yield and nutritional value. Developing high-yielding and nutritionally superior hybrids is increasingly vital in the face of climate change and rising global forage demand. Doubled haploid (DH) technology accelerates hybrid development by enabling the rapid production of fully homozygous pure lines. This study aimed to evaluate silage maize hybrids derived from DH inbred lines for the effects of yield and nutritional quality.MethodsEight recently developed hybrids (derived from doubled haploid inbred lines: S1, S2, S6, S9, and S11; derived from conventional inbred lines: S7, S8, and S10) and four commercial silage checks (S3, S4, S5, and S12) were used in this study. The experiments were arranged in a randomized complete block design with three replications. In this study, agronomic traits including plant height, ear ratio, stem ratio, and forage yield were evaluated, along with forage quality parameters such as dry matter, crude protein, neutral detergent fiber (NDF), acid detergent fiber (ADF), acid detergent lignin (ADL), and relative feed value.ResultsGenotypes S6 and S9 provided higher forage yield, plant height, ear ratio, and a lower stem ratio. All genotypes of dry matter, crude protein, NDF, and ADF values were within the desired range. DH-derived hybrids outperformed checks and those derived from conventional inbred lines regarding forage yield and the investigated agronomic traits. The DH technology has great potential in developing high-yielding hybrids in a short time in silage maize breeding.
creator: Sinem Zere Taşkın
creator: Ahmet Duman
creator: Uğur Bilgili
uri: https://doi.org/10.7717/peerj.20197
license: https://creativecommons.org/licenses/by/4.0/
rights: © 2025 Zere Taşkın et al.

title: Effects of exercise intervention on falls and balance function in older adults: a systematic review and meta-analysis
link: https://peerj.com/articles/20190
last-modified: 2025-10-17
description: ObjectiveTo systematically review the effects of an exercise intervention on falls and balance function in older adults (aged > 60 years) without diagnosed diseases.MethodsPubMed, Web of Science, Embase, Cochrane Library, and CNKI databases were searched for randomized controlled trials about exercise intervention on falls and balance function in older adults. Use Review Manager 5.4 to test the risk bias in the included literature, and use Stata17 for publication bias test, sensitivity analysis, combining effect sizes, forest plots, and subgroup analysis.ResultsA total of 37 randomized controlled trials were included, and meta-analysis showed that after the exercise intervention in the intervention group, there was a significant increase in the Modified Fall Efficacy Scale (MFES) score (g = 1.01, 95% confidence interval (CI) [0.63–1.40], P = 0.00), the number of falls (odds ratio (OR) = 0.32, 95% CI [0.20–0.51], P = 0.00), the Berg Balance Scale (BBS) score (g = 0.92, 95% CI [0.63–1.21], P = 0.00) and Timed Up and Go Test (g = −0.62, 95% CI [−0.80, −0.45], P = 0.00) indices improved better than the control group. Subgroup analysis showed that single exercise time > 30 min, 3 times per week for 12–23 weeks was the better intervention for fall efficacy in older adults, and single exercise time ≤ 30 min, 3 times per week for ≥ 24 weeks was the better intervention for balance function in older adults.ConclusionExercise intervention can enhance fall efficacy, reduce the number of falls, and improve balance function in older adults, and have a certain preventive effect on falls. Single exercise time, exercise frequency and exercise cycle are important factors affecting the effectiveness of exercise intervention. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42024590937.
creator: Haoran Yu
creator: Jianwei Zhong
creator: Min Li
creator: Shuainan Chen
uri: https://doi.org/10.7717/peerj.20190
license: https://creativecommons.org/licenses/by/4.0/
rights: ©2025 Yu et al.

title: Prevalence and risk factors of sarcopenia and effect of sarcopenia on functional status and falls incidents among the elderly in Selangor
link: https://peerj.com/articles/20175
last-modified: 2025-10-17
description: BackgroundThe burden of sarcopenia is increasing but studies on sarcopenia at the population level are limited in Malaysia. This study was conducted to identify the prevalence, risk factors and effect of sarcopenia on functional status and falls among the elderly in Selangor state.MethodsAnthropometry, body composition measurements and face-to-face interview using questionnaires on functional status and falls were conducted on 469 respondents. Prior to the interview, written informed consent was obtained from the respondents. The inclusion criteria for this study is being 60-years old and above, able to understand, read and speak Bahasa Malaysia or English language and voluntarily consents to participates in the study. Multifrequency bioelectrical impedance analysis (BIA) was used to measure the body composition. Sarcopenia assessment was done using the guideline from Asian Working Group for Sarcopenia (AWGS) 2019.ResultsThe prevalence of possible sarcopenia, confirmed sarcopenia and severe sarcopenia were 38.4%, 10.0% and 24.5%, respectively. Prevalence of activities of daily living (ADL) and instrumental activities of daily living (IADL) dependence were 26.0% and 25.4%, respectively and 42.2% of the respondents experienced falls in the last 12 months. Multinomial logistic regression model showed that locality (AOR = 2.90; p < 0.001), type-2 diabetes mellitus (adjusted odds ratio (AOR) = 1.87; p = 0.031) and female gender (AOR = 2.58; p < 0.001) were significantly associated with possible sarcopenia. Female gender (AOR = 3.04; p = 0.005) and depression (AOR = 3.27; p = 0.048) were significantly associated with confirmed sarcopenia, where else hypertension (AOR = 0.45; p = 0.039) were found to be a protective factor for confirmed sarcopenia. Age (AOR = 4.52; p < 0.001), female gender (AOR = 1.84; p = 0.045), race (AOR = 3.82; p = 0.001), locality (AOR = 3.82; p < 0.001), level of education (AOR = 5.32; p = 0.010) and physical activity (AOR = 2.28; p = 0.029) were significantly associated with severe sarcopenia. The respondents with confirmed sarcopenia and severe sarcopenia were significantly associated with ADL (AOR = 10.54; p < 0.001) and IADL (AOR = 8.55; p < 0.001) dependence after adjustment for the covariates. In addition, after adjusting for covariates, respondents with possible sarcopenia (AOR = 3.34; p < 0.001) and respondents with confirmed sarcopenia and severe sarcopenia (AOR = 10.62; p < 0.001) were significantly associated with falls incidents.ConclusionsThe findings from this study highlights the detrimental effects of sarcopenia and the importance of early detection at the community level.
creator: Thinakaran Kandayah
creator: Nazarudin Safian
creator: Shamsul Azhar Shah
uri: https://doi.org/10.7717/peerj.20175
license: https://creativecommons.org/publicdomain/zero/1.0/
rights: 

title: Remarkable dominance of myctophid otoliths in Upper Miocene Chagres Formation, Caribbean Panama
link: https://peerj.com/articles/20155
last-modified: 2025-10-17
description: Marine fossils from the Upper Miocene Chagres Formation in northern Panama offer critical insights into the paleoenvironmental conditions and ecological responses prior to the separation of the Atlantic from the Pacific by the formation of the Isthmus of Panama. Here we present a systematic study based on more than 6,200 otoliths collected from a coastal exposure near the town of Piña, Colón. This assemblage is remarkable for the extraordinary dominance of the family Myctophidae, constituting over 96% of specimens. The otolith density in the sediments is among the richest known globally (278.80 ± 135.59 otoliths/kg). The taxonomic composition is represented by 31 taxa across 12 families, including four new species: namely Chiloconger aflorens sp. nov., Dasyscopelus inopinatus sp. nov., Hoplostethus boyae sp. nov., and Malakichthys schwarzhansi sp. nov. Taphonomic evidence, combined with abundant predatory marine vertebrate fossils and extensive burrow ichnofossils, indicates a dynamic and highly productive nearshore ecosystem. The dominance of myctophids and multiple lines of evidence support the existence of a Late Miocene coastal upwelling system in the region, highlighted by efficient trophic transfer channeled from high primary production to apex predators. These findings provide a nuanced understanding of Neogene marine ecosystems prior to the final emergence of the Isthmus of Panama.
creator: Chien-Hsiang Lin
creator: Aaron O’Dea
uri: https://doi.org/10.7717/peerj.20155
license: https://creativecommons.org/licenses/by/4.0/
rights: ©2025 Lin and O’Dea