title: PeerJ description: Articles published in PeerJ link: https://peerj.com/articles/index.rss3?journal=peerj&page=13 creator: info@peerj.com PeerJ errorsTo: info@peerj.com PeerJ language: en title: Real-world efficacy assessment for sintilimab in recurrent or metastatic cervical cancer link: https://peerj.com/articles/20477 last-modified: 2025-12-19 description: BackgroundProgrammed death 1 (PD-1) monoclonal antibodies have been reported as a first-line therapeutic option for recurrent cervical cancer, especially for programmed death ligand 1 (PD-L1)-positive tumors. However, real-world data on the use of PD-1 monoclonal antibodies in patients with an undefined PD-L1 status is scarce. This study analyzed the efficacy and safety of sintilimab in patients with recurrent or metastatic cervical cancer.MethodsData of patients who received sintilimab for the first time in the First Affiliated Hospital of the Army Medical University from November 2019 to July 2022 were collected. The efficacy and safety of sintilimab were evaluated according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, respectively. The Kaplan–Meier curve and log-rank test were used to analyze patient survival.ResultsTwenty-seven (27) patients were included in the study. The median follow-up was 17 (range, 6–40) months. The objective response rate (ORR) and disease control rate (DCR) were 69.6% and 87.0%, respectively, in efficacy-evaluable patients. The ORR of the combination therapy was significantly higher than that of the monotherapy (82.3% vs. 33.3%, P = 0.045). The ORR was 91.7% for patients who initiated treatment within two months and 37.5% for those who started treatment after two months (P = 0.018). In the intention-to-treat population, 55.5% of the patients experienced adverse events, and 14.8% of the patients had grade 3 or higher treatment-related adverse events.ConclusionsSintilimab appeared to demonstrate satisfactory efficacy and safety in the study. The combination therapy showed a higher ORR compared to monotherapy. Furthermore, early initiation of sintilimab as first-line therapy within two months following recurrence is more effective compared to delayed initiation beyond this period in patients with recurrent disease. creator: Dan Zhou creator: Ruiwei Wang creator: Lingjun Huang creator: Ping Yan creator: Kaijian Ling creator: Zhiqing Liang uri: https://doi.org/10.7717/peerj.20477 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2025 Zhou et al. title: Rational deployment of molecular markers for the benzenediol lactones and related compounds biosynthesis in filamentous fungi link: https://peerj.com/articles/20472 last-modified: 2025-12-19 description: Fungal benzenediol lactones (BDLs) are hydrophobic secondary metabolites that include the mycotoxin zearalenone, the phytotoxin curvularin, and related compounds such as cytosporones and cladosporin. The extensive diversity of macrolactones likely reflects long-standing microbial competition for resource-limited niches. We screened 97 fungal isolates for highly reducing polyketide synthases (HR-PKSs) implicated in BDL biosynthesis, designed degenerate markers for conserved HR-PKS domains, and validated them in silico against 1,039 reference genomes. To automate candidate selection, we developed a customizable pipeline for classifying nucleotide or protein sequences by phylogenetic placement on a curated reference tree (https://github.com/gkoczyk/micro_phyloplace). Phylogenetic placement of amplicons against a large set of reference PKSs identified putative BDL/BDL-like compound producers among known and previously uninvestigated genera in Diaporthales (Coniella, Diaporthe, Diaporthella, Valsa), Hypocreales (Fusarium, Ilyonectria, Pochonia), as well as Curvularia, Penicillium, Phoma and Talaromyces spp., demonstrating utility for environmental screening. Our analysis underscores both the efficacy and challenges of amplification with degenerate primers; nevertheless, phylogenetic placement offers a viable, low-cost screen for targeted subsets of highly diverse gene families. creator: Michał Kawaliło creator: Justyna Lalak-Kańczugowska creator: Zuzanna Dutkiewicz creator: Monika Urbaniak creator: Delfina Popiel creator: Katarzyna Czyż creator: Grzegorz Koczyk uri: https://doi.org/10.7717/peerj.20472 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2025 Kawaliło et al. title: Copper metabolism-related biomarkers and therapeutic targets for diabetic nephropathy link: https://peerj.com/articles/20468 last-modified: 2025-12-19 description: BackgroundDiabetic nephropathy (DN) is the most intractable complication of diabetes. Despite decades of research, accurate diagnostic markers and effective therapeutic drugs are still elusive. Abnormal copper metabolism is also implicated in diabetes and its complications. This study aims to identify copper metabolism-related biomarkers and potential drugs for DN.MethodsDN datasets and copper metabolism-related genes (CMGs) were obtained from Gene Expression Omnibus (GEO) and GeneCards. Differentially expressed CMGs (DE-CMGs) were identified using the limma package and the Venn algorithm. Functional enrichment analysis and protein-protein interaction (PPI) network were performed to identify candidate hub genes. The single gene with an area under the receiver operating characteristic (ROC) curve > 0.7 was identified as a potential diagnostic biomarker of DN. Finally, these biomarkers were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in high-glucose-treated human proximal tubular (HK-2) cells. These validated hub genes were used to construct a combined prediction model, confirmed by additional GSE30528 and GSE30529 datasets. The correlation analysis between the expression level of the hub genes and the estimated glomerular filtration rate (eGFR) was carried out. Additionally, immune cell infiltration and potential target drugs were investigated for these biomarkers.ResultsFive hub genes associated with copper metabolism, namely CD36, CCL2, CASP3, LPL, and APOC3, were identified as biomarkers for the early diagnosis of DN. Utilizing multiple biomarkers enhanced diagnostic accuracy and specificity. CD36, CCL2, and CASP3 correlated negatively with eGFR levels, while LPL and APOC3 correlated positively. Additionally, these hub genes were significantly linked to various immune cell types, including macrophages M1 and M2, T cells, gamma delta resting dendritic cells, neutrophils, and NK cells. Furthermore, 15 agents targeting these biomarkers were retrieved from the DrugBank database.ConclusionOur study identified key genes possibly related to copper metabolism in the pathological mechanism of DN that could serve as novel targets for the diagnosis and therapy of DN. creator: Qiaofang Yan creator: Yuanyuan Du creator: Fei Huang creator: Min Zhan creator: Qifan Zheng creator: Qiaoxuan Zhang creator: Pengwei Zhang creator: Jun Yan creator: Xiaobin Wu creator: Haibiao Lin creator: Xianzhang Huang creator: Liqiao Han uri: https://doi.org/10.7717/peerj.20468 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2025 Yan et al. title: Identification of hypoxia- and mitochondria-related genes associated with recurrent spontaneous abortion: an integrative bioinformatics analysis and preliminary validation link: https://peerj.com/articles/20467 last-modified: 2025-12-19 description: BackgroundHypoxia and mitochondrial dysfunction have been implicated in recurrent spontaneous abortion (RSA), although the precise molecular mechanisms remain unclear. This study aimed to explore hypoxia- and mitochondria-related genes (HRGs and MRGs) that may be associated with RSA using integrative bioinformatics approaches and preliminary experimental validation.MethodsWe analyzed transcriptomic data and curated a list of HRGs/MRGs, and subsequently identified differentially expressed genes (DEGs) between the RSA and control groups. Overlapping DEGs with HRGs and MRGs revealed candidate genes, which were further validated through machine learning and expression analysis. A nomogram was developed to predict RSA risk based on these genes. Additionally, functional enrichment analysis, immune infiltration profiling, and regulatory network analysis were performed, followed by drug prediction. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) confirmed the differential expression of genes.ResultsBSG and TRAK1 were identified, via bioinformatics and RT-qPCR validation, as hypoxia- and mitochondria-related genes associated with RSA. Gene Set Enrichment Analysis (GSEA) suggested that BSG and TRAK1 may be associated with biological pathways such as zinc ion homeostasis and NK cell-mediated cytotoxicity, although their mechanistic roles remain unclear. The nomogram exhibited strong predictive accuracy. BSG and TRAK1 were positively correlated with resting memory CD4+ T cells, with their expression regulated by transcription factors EHMT2 and SUPT5H. Drug prediction analyses, based on gene expression patterns, suggested captopril, valproic acid, and compound 7646-79-9 as potential candidates for future experimental investigation, although their mechanistic roles remain to be validated.ConclusionBSG and TRAK1 are upregulated in RSA and associated with RSA-relevant biological processes. While their functional roles require further investigation, these genes represent promising candidates for future mechanistic and clinical studies. creator: Lin Chen creator: Caini Wei creator: Lili Gao creator: Dongyang Lu uri: https://doi.org/10.7717/peerj.20467 license: https://creativecommons.org/licenses/by-nc/4.0 rights: ©2025 Chen et al. title: Effects and safety of vibration therapy in knee osteoarthritis rehabilitation: an umbrella review of systematic reviews link: https://peerj.com/articles/20455 last-modified: 2025-12-19 description: ObjectiveKnee osteoarthritis (KOA) is a prevalent degenerative joint disease characterized by pain, stiffness, and limited mobility, substantially impairing quality of life. Vibration therapy has gained attention as a promising nonpharmacological intervention for KOA management. However, existing systematic reviews report inconsistent findings regarding its efficacy and safety. This umbrella review synthesizes evidence from published systematic reviews to provide a comprehensive evaluation of vibration therapy in KOA.MethodsA systematic search was conducted in four electronic databases: PubMed, Physiotherapy Evidence Database (PEDro), Web of Science, and Embase, with the search completed in January 2025. Eligible systematic reviews, with or without meta-analyses, examining the effects of vibration therapy in KOA were included. Two independent reviewers screened titles and abstracts, assessed full text eligibility, and extracted data on study characteristics, interventions, and clinical outcomes. The methodological quality of the included reviews was assessed using the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) tool, and reviews were categorized as high, moderate, or low quality. Study overlap was evaluated using the Corrected Covered Area (CCA) method to quantify redundancy. Findings were synthesized qualitatively, focusing on outcomes related to pain intensity, physical function, functional mobility and KOA-related disability.ResultsSix systematic reviews published between 2015 and 2022 met the inclusion criteria, of which five included meta-analyses. In total, 22 unique primary trials were cumulatively analysed. The average AMSTAR-2 score was 65.7%, ranging from 56% (moderate) to 81% (high quality). The CCA analysis revealed a high degree of overlap (15%) across the reviews, indicating redundancy in primary studies but also reinforcing consistency in evidence. Commonly reported outcomes included the Visual Analogue Scale, muscle strength, Berg Balance Scale, Six Minute Walk Test, Timed Up and Go test, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). The majority of reviews reported favourable effects of vibration therapy on WOMAC physical function and pain intensity, while fewer reviews supported improvements in functional performance and muscle strength.ConclusionVibration therapy appears to be a promising adjunct to conventional rehabilitation for KOA, particularly for improving physical function and knee pain. However, inconsistent evidence regarding its effects on functional performance and muscle strength underscores the need for further high-quality research. Future studies should determine optimal vibration parameters and explore underlying mechanisms to establish evidence based clinical guidelines.Review RegistrationPROSPEROCRD42024620119. creator: Yan Peng creator: Mohd Azzuan Ahmad creator: Yulong Xie creator: Zhenkun Xu creator: Siaw Chui Chai uri: https://doi.org/10.7717/peerj.20455 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2025 Peng et al. title: A systematic review of global publications on clouded leopard (Neofelis nebulosa): identifying the publication trends, research gaps, and future directions to strengthen its conservation link: https://peerj.com/articles/20421 last-modified: 2025-12-19 description: BackgroundDespite global investment in studying, protecting, and managing carnivores, species like the clouded leopard Neofelis nebulosa (Griffith, 1821), renowned for its elusive nature, remain significantly understudied. There is also insufficient knowledge of clouded leopard research trends in spatial and temporal domains. Additionally, thematic areas of research on this species are not clearly known. This gap in information may hinder the development of effective strategies to address key conservation challenges such as habitat loss, poaching, and illegal trade.MethodsTo bridge these gaps, we systematically reviewed 123 peer-reviewed journal articles published up to December 2022, offering critical insights into the current state of knowledge and identifying future research priorities to inform conservation planning.ResultsThe spatial analysis of clouded leopard research reveals that Thailand (n = 28) dominates the range countries, while the USA (n = 26) dominates non-range countries in terms of research efforts. Temporally, research output has shown a significant increase since 2006, peaking in 2016 (n = 13), with a positive trend in publications (Kendall’s tau = 0.52, P < 0.001). Most studies focused on anatomy and physiology in captive populations (n = 31) and habitat use and distribution in free-ranging populations (n = 23). The studies on the impact of climate change on the clouded leopard and its habitat, alongside feeding ecology, remain scant, necessitating the future research in these areas. Our analysis also revealed that the maximum number of publications employed diagnosis and treatment (26%), followed by camera trapping (24.4%). We recommend integrating local ecological knowledge and monitoring technologies to map the clouded leopard’s corridors, connectivity, and bottleneck sites at the landscape level. A higher number of publications addressed habitat loss and illegal trade as the primary threats to clouded leopard conservation. Effective law enforcement, proper land use, land cover planning, and community engagement are crucial for conserving this species. Moreover, clouded leopard range countries are recommended to develop sustainable financial mechanisms and implement the conservation action plan across the country, which can improve conservation outcomes. creator: Nikita Phuyal creator: Nishan Kc creator: Neeta Pokharel creator: Shreejan Gautam creator: Nitu Adhikari creator: Bijaya Dhami creator: Saurav Lamichhane creator: Mahamad Sayab Miya creator: Abhinaya Pathak creator: Bijaya Neupane uri: https://doi.org/10.7717/peerj.20421 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2025 Phuyal et al. title: Phosphorus fractionation and distribution in Nitisols of the central Ethiopian highlands affects soil nutrient management strategies in barley (Hordeum vulgare L.) production link: https://peerj.com/articles/20410 last-modified: 2025-12-19 description: Optimizing nutrient management is essential for sustaining crop productivity on fertilizer-unresponsive acidic soils, particularly through a comprehensive understanding of soil phosphorus (P) dynamics. Phosphorus availability is often limited by soil physicochemical properties, necessitating site-specific amendment strategies. This study evaluated the status of inorganic P fractions and their response to various nutrient and soil amendment treatments in acidic Nitisols from Welmera and Ejere districts in the central Ethiopian highlands, with a focus on barley (Hordeum vulgare), a crop that is sensitive to low soil pH. Field and laboratory investigations revealed that strongly acidic soils responded positively to lime application combined with optimal P fertilization, resulting in significant yield improvements. In contrast, moderately to slightly acidic soils exhibited limited response to liming but showed enhanced productivity following organic amendments such as compost. Soil management strategies including the application of inorganic phosphorus fertilizers, increased barley yield to 3479 kg ha−1. Additionally, soil amendments such as agricultural lime improved barley productivity by enhancing the availability of plant-accessible phosphorus. Sequential phosphorus fractionation revealed that iron-bound and occluded P fractions dominated the inorganic P pool, accounting for approximately 45% and 35% of total inorganic P, respectively. Higher level of aluminum-bound P was also observed in strongly acidic soils. higher water-soluble P represented only about 3% of total inorganic P, highlighting the limited readily available P fraction. These findings emphasize the critical role of detailed P fractionation analysis in informing targeted nutrient management strategies to improve P availability, thereby supporting sustainable soil fertility and crop production, particularly barley under acidic soil conditions. creator: Matiyas Dejene Girma creator: Miheretu Bedassa Wakessa uri: https://doi.org/10.7717/peerj.20410 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2025 Girma and Wakessa title: Core muscle endurance and psychosocial factors affecting functional mobility in chronic low back pain: cross-sectional results link: https://peerj.com/articles/20372 last-modified: 2025-12-19 description: BackgroundThe functional limitations associated with chronic low back pain (CLBP) are substantial and are highly correlated with core muscle endurance and psychosocial factors. Core muscle endurance is known to affect physical performance, whereas pain catastrophizing and fear avoidance beliefs can contribute to disability. A comprehensive understanding of the interrelated impact of these factors is critical for developing effective rehabilitative strategies. The study aimed to (1) examine the correlation between core muscle endurance and functional mobility in CLBP subjects and (2) explore the influence of psychosocial factors, pain catastrophizing, and fear-avoidance beliefs on that correlation.MethodsA cross-sectional study was conducted on 136 adults; core muscle endurance was measured by plank, side-bridge, and back extensor tests. The timed up and go (TUG) and five times sit-to-stand test (5TSTS) were utilized to evaluate functional mobility. Pain intensity was assessed using the visual analog scale (VAS), and disability using the Oswestry disability index (ODI). Psychosocial factors were measured using the pain catastrophizing scale (PCS) and the fear-avoidance beliefs questionnaire (FABQ).ResultsCore muscle endurance measures were moderately correlated with functional mobility outcomes (TUG: r = −0.42 to −0.50, p < 0.05; 5TSTS: r =  − 0.35 to −0.43, p < 0.05). Hierarchical regression showed muscle endurance accounted for 32% of the variance in mobility, while adding psychosocial factors increased the adjusted R2 to 0.52 (p < 0.05). High-psychosocial-risk subgroups analyzed within the study had poorer mobility (TUG: 9.45 ± 1.32 vs. 7.89 ± 1.21 s; p = 0.001).ConclusionPsychosocial factors and endurance of the core muscles in CLBP can significantly predict functional mobility. Integrating physical and psychological rehabilitation strategies might improve mobility outcomes, bolster human dignity, and enhance quality of life. creator: Ravi Shankar Reddy creator: Mastour Saeed Alshahrani creator: Hani Hassan Alnakhli creator: Batool Abdulelah Alkhamis creator: Ghada Mohamed Koura creator: Debjani Mukherjee creator: Raee S. Alqhtani creator: Faisal M. Alyazedi creator: Amal Fahad Al Mukhid creator: Saeed Ahmed M. Alhudiry uri: https://doi.org/10.7717/peerj.20372 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2025 Reddy et al. title: Proprioception and muscle performance unchanged by in-home step training in multiple sclerosis: secondary outcomes analysis link: https://peerj.com/articles/20354 last-modified: 2025-12-19 description: BackgroundThe Interactive Step Training to Reduce Falls in People with Multiple Sclerosis (iFIMS) trial was a multi-centre, parallel-designed, randomised controlled trial testing an in-home, computerised exergame playing system (smart±step) in people with multiple sclerosis (Expanded Disability Status Scale 2–6).ObjectiveThis study was nested within the iFIMS trial to assess whether the smart±step system could improve secondary outcomes of ankle proprioception and plantarflexor muscle performance.MethodsTests of ankle proprioception and plantarflexor muscle performance were performed before and after 6 months of intervention with the smart±step system (intervention group; n = 33), or 6 months of usual care (control group; n = 33). Ankle proprioception outcomes included movement detection threshold and reaction time. Plantarflexor muscle performance outcomes included maximal voluntary torque, twitch torque from electrical stimulation, voluntary activation (level of neural drive), decrease in these parameters after a 2-min sustained isometric contraction, and time-to-recovery of these parameters.ResultsThere were no differences between the intervention and control groups for all proprioception and muscle performance outcomes (95% CI of mean differences crossed 0), and no difference in time-to-recovery after the sustained contraction (95% CI of hazard ratios crossed 1).ConclusionsThe smart±step system did not improve proprioception or muscle performance over a 6-month intervention, compared to usual care, in people with multiple sclerosis. However, at-home interventions are cost effective and convenient, and the smart±step system could help maintain physical activity in an engaging way in this group. creator: Zoë J. Djajadikarta creator: Siobhan C. Dongés creator: Joanna Diong creator: Phu D. Hoang creator: David S. Kennedy creator: Jasmine C. Menant creator: Stephen R. Lord creator: Janet L. Taylor creator: Simon C. Gandevia uri: https://doi.org/10.7717/peerj.20354 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2025 Djajadikarta et al. title: Fish community structure and diversity in the Ningxia section of the main stream of the Yellow River in China link: https://peerj.com/articles/20228 last-modified: 2025-12-19 description: The Ningxia section of the Yellow River represents a critical habitat for freshwater fish biodiversity, yet its ecological integrity faces increasing threats from anthropogenic activities. To comprehensively assess the fish community structure, diversity, and its relationship with environmental factors in the Ningxia section of the Yellow River, we conducted seasonal surveys of fish resources and environmental conditions at 15 selected sites from July 2022 to September 2023. Our study employed quantitative analyses to evaluate fish community characteristics, spatiotemporal distribution patterns, and their interactions with environmental variables. A total of 42 fish species, belonging to 34 genera, 11 families, and six orders, were identified, with Cyprinidae being the dominant family (57.14%). Carnivorous species were the most abundant (22 species), followed by omnivorous (16 species) and herbivorous (four species) fish. The Relative Importance Index (IRI) identified Gobio huanghensis and Carassius auratus as the dominant species in this region. Biodiversity indices revealed a mean Margalef richness index of 3.066, Pielou evenness index of 0.5911, Shannon-Wiener diversity index of 1.791, and Simpson dominance index of 0.7083. The Abundance-Biomass Comparison (ABC) curve indicated moderate disturbances to fish communities in spring and autumn, while communities remained stable in summer and winter. Spatially, six sites (Nanchangtan, Shapotou, Jinshawan, Meijiawan, Linhe, and Taole) exhibited significant disturbances, while others showed moderate or stable conditions. The results of cluster analysis and non-metric multidimensional scaling (NMDs) indicated no significant differences in fish community structure among the sampling sections in the Ningxia reach of the Yellow River. Redundancy analysis (RDA) identified water temperature and ammonia nitrogen as the primary environmental factors influencing fish community structure. Our findings highlight the combined impacts of human activities and environmental changes on fish communities in the Ningxia section of the Yellow River. These results provide a scientific basis for the conservation and sustainable management of fishery resources in this ecologically sensitive region. creator: Jiacheng Liu creator: Shuhan Xiong creator: Peilun Li creator: Yanbin Liu creator: Yongjie Wang creator: Kai Liu creator: Jilong Wang uri: https://doi.org/10.7717/peerj.20228 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2025 Liu et al.