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전체arXiv CS.AI6,534arXiv Math6,523arXiv Physics2,314arXiv Stat1,122PLOS ONE453arXiv Q-Bio318arXiv Econ316PLOS Global Public Health64PLOS Biology29PLOS Medicine14
PLOS ONE

Visualization of grout diffusion in coarse-grained materials using transparent soil: Effects of Fine particle content

by Shihao Zhang, Jianxin Wang, Zhuo Li, Yusheng Li Fine-particle loss in earth-rock dams can induce abnormal grout diffusion during rehabilitation. To address this issue, we investigated the influence of fine particle content on grouting efficiency in coarse-grained materials. Using transparent soil technology, coarse-grained materials were simulated with fused quartz sand and a refractive-index-matched pore fluid (n = 1.4585). Dyed epoxy resin was used as a cement grout analog. Constant-pressure grouting tests (40 kPa) were performed on three test conditions representing no fine-particle loss, partial fine-pareicle loss, and complete fine-particle loss. The grout diffusion process was visualized and quantified using Particle Image Velocimetry (PIV). The results reveal that fine particle content critically controls grout diffusion patterns and rates. (1) Excessive fines cause pore clogging, resulting in grout upwelling, surface seepage, and limited diffusion, forming locally consolidated masses with blocky bonding. (2) An appropriate fine particle content enables uniform spherical diffusion, creating an optimized structure characterized by point bonding of large particles and small-pore filling. (3) The absence of fines leads to gravity-dominated rapid settlement with weak horizontal diffusion, leaving only surface-coated particles. This study elucidates the coupled mechanisms of fine-particle migration, clogging, and grout diffusion, providing an experimental basis for optimizing permeation grouting in coarse aggregates.

PLOS ONE

Residual-guided hybrid framework for adversarially robust deep learning-based network intrusion detection

by Sudip Saha, Muhammad Arslan Pervaiz, Muhammad Safwat Rahman, Shahriar Ahmmed, Jannatul Maua The growing sophistication of cyber threats and adversarial attacks poses critical challenges to the security and robustness of machine learning models deployed in real-world systems. While traditional deep learning architectures excel in clean data classification, they often fail under adversarial perturbations, exposing vulnerabilities in sensitive domains such as healthcare, finance, and industrial control. In this paper, we introduce a novel hybrid adversarially-trained deep learning framework that integrates reinforcement learning-inspired robustness adaptation with knowledge-driven regularization to achieve improved resilience against fast gradient sign method (FGSM) and projected gradient descent (PGD) attacks. Our approach simultaneously optimizes clean accuracy and adversarial robustness by balancing cross-entropy and adversarial loss components, while monitoring calibration error, gradient dynamics, and generalization gap to ensure stable convergence. Extensive experiments on reconnaissance, shellcode, and worms datasets demonstrate that the proposed model achieves up to 97.88% accuracy on clean data and maintains 84.9% accuracy under FGSM and 81.75% under PGD attacks, outperforming convolutional neural network (CNN) and long short-term memory (LSTM) baselines by more than 6–10 percentage points in adversarial robustness. Furthermore, the training curves reveal consistent improvements in convergence stability, runtime efficiency, gradient norm decay, and a 30% reduction in expected calibration error, validating the scalability of the framework. This work contributes not only a novel adversarial defense paradigm but also provides insights into the trade-offs between robustness, efficiency, and generalization.

PLOS ONE

Expression of Concern: Deciphering Transcriptional Programming during Pod and Seed Development Using RNA-Seq in Pigeonpea (<i>Cajanus cajan</i>)

by The PLOS One Editors

PLOS ONE

Expression of Concern: Genetic Diversity and Demographic History of <i>Cajanus spp.</i> Illustrated from Genome-Wide SNPs

by The PLOS One Editors

PLOS ONE

Expression of Concern: An Integrated SNP Mining and Utilization (ISMU) Pipeline for Next Generation Sequencing Data

by The PLOS One Editors

PLOS ONE

Experimental and quantitative observational research in fencing and wheelchair fencing: A scoping review

by Katharine Holmes, Lindsay Bottoms Background Fencing and wheelchair fencing are Olympic and Paralympic sports with growing global participation and increasing scientific interest. However, the overall structure, methodological profile, and thematic distribution of experimental and quantitative observational research in both has not been systematically characterized. Objective To map the scope, methodological characteristics, and thematic focus of experimental and quantitative observational studies involving fencing and wheelchair fencing athletes. Methods A scoping review was conducted in accordance with PRISMA-ScR guidelines. PubMed, Scopus, and EBSCOhost were searched for studies containing the terms “fencing,” “fencer,” or “fencers” in the title or abstract. Eligible studies employed experimental or quantitative observational designs and included fencing athletes as participants. Data were extracted using a structured framework and summarized descriptively across study design, research domain, participant characteristics, sample size, weapon discipline, and geographic distribution. Results A total of 445 studies met inclusion criteria. Publication volume increased substantially after 2015. Laboratory-based (35.7%) and cross-sectional (30.3%) designs predominated, whereas prospective cohort studies (5.4%) and randomized controlled trials (4.3%) were comparatively uncommon. Performance and skill analysis constituted the largest research domain (41.1%), while injury/epidemiology (7.9%), recovery/rehabilitation (4.3%), and training load/fatigue (1.6%) research were limited. Most studies involved small sample sizes with fewer than 50 participants and focused on able-bodied athletes; wheelchair fencing was markedly underrepresented. Sex was not specified in 24.3% of studies, and weapon discipline was not reported in 44.9%. Research output was geographically concentrated in Europe and select North American and East Asian countries. Conclusions Although fencing research has expanded rapidly in recent years, it remains methodologically and thematically uneven. Greater emphasis on longitudinal and interventional designs, injury surveillance, rehabilitation research, improved reporting practices, and inclusive representation across sex, weapon discipline, geographic regions, and wheelchair athletes are necessary to strengthen the translational relevance and evidence-based development of fencing sport science.

PLOS ONE

Association between frailty status and osteomyelitis: A nested case-control study

by Can Guo, Xukun Luo, Zijin Tang, Jian Zhou, Tang Liu Background Although frailty has been recognized as a predictor of various adverse outcomes in older adults, the association between physical pre-frailty or frailty and the risk of osteomyelitis remains unclear. Methods In this nested case-control study, data from 466,918 eligible participants recruited into the UK Biobank between 2006 and 2010 were used. Incident osteomyelitis cases were identified through linked electronic health records up to 19 December 2022 and matched to controls at a 1:5 ratio by age, sex, and assessment center from the baseline population meeting the eligibility criteria. Frailty status was assessed at baseline using a five-item phenotype adapted from the Fried criteria and categorized as non-frail, pre-frail, or frail. Conditional logistic regression was used to evaluate the association between frailty status and osteomyelitis after adjustment for socioeconomic factors, lifestyle behaviors, medication use, and clinical risk factors. Results Compared with non-frail individuals, participants with physical pre-frailty had a significantly higher odds of osteomyelitis (OR = 1.38; 95% CI: 1.16–1.64), with the odds further increasing among those with physical frailty (OR = 2.79; 95% CI: 2.05–3.81), demonstrating a clear dose–response relationship (P-trend <0.001). These associations between physical frailty status and osteomyelitis remained robust across subgroups defined by potential risk factors. Conclusions Physical pre-frailty and frailty were associated with higher odds of osteomyelitis, with the odds increasing across frailty categories.

PLOS ONE

Potent and broad-spectrum anti-<i>Candida</i> activity of 6α-(3’-methoxy-4’-hydroxybenzoyl)-lup-20(29)-ene-3-one, a triterpenoid from <i>Paullinia pinnata</i>

by Benjamin Kingsley Harley, Inemesit Okon Ben, Theophilus Duku Asamoah, Cedric Dzidzor K. Amengor, Nii Korley Kortei, Priscilla Eghan, Theophilus Christian Fleischer Vulvovaginal candidiasis is a common infection that affects women of reproductive age, with a high prevalence among pregnant women. When left untreated, it can lead to pregnancy complications including miscarriage. The study evaluated the activity of the ethyl acetate (EtOAc) extract of Paullinia pinnata and its isolated compound 6α-(3’-methoxy-4’-hydroxybenzoyl)-lup-20(29)-ene-3-one against drug-resistant strains and clinical isolates of Candida albicans, Candida glabrata, Candida krusei, Candida parapsilosis and Candida tropicalis. Furthermore, the effects of the combinations of 6α-(3’-methoxy-4’-hydroxybenzoyl)-lup-20(29)-ene-3-one with voriconazole, nystatin or caspofungin on the Candida strains and isolates as well as its antibiofilm activity against the drug-resistant strains are reported in this study. The EtOAc leaves extract of P. pinnata demonstrated considerable activity against the drug-resistant Candida strains and clinical isolates with minimum inhibitory concentrations (MICs) of 31.25 to 500 µg/mL when assessed for anti-Candida activity using the microbroth dilution method. The extract was column fractionated to obtain five bulk fractions, and from the most active bulk fraction, BF4 (MIC = 3.91–31.25 µg/mL), 6α-(3’-methoxy-4’-hydroxybenzoyl)-lup-20(29)-ene-3-one was isolated. This study is the first reported biological activity of the compound. 6α-(3’-methoxy-4’-hydroxybenzoyl)-lup-20(29)-ene-3-one exhibited strong activity against the panel of drug-resistant Candida species with MIC ranging from 0.5 to 16 µg/mL (0.85–27.10 µM). This activity was within similar range to that of ketoconazole (MIC = 1–8 µg/mL) and amphotericin B (MIC = 0.5–2 µg/mL). When combined with voriconazole, nystatin or caspofungin using the checkerboard assay, 6α-(3’-methoxy-4’-hydroxybenzoyl)-lup-20(29)-ene-3-one recorded synergism of 33.33% to 83.33% with the antifungals, with majority of the synergistic interactions observed against C. albicans and C. glabrata strains and isolates. 6α-(3’-methoxy-4’-hydroxybenzoyl)-lup-20(29)-ene-3-one also demonstrated anti-biofilm activity. Its IC50 values against the formation of biofilms and preformed biofilms of the Candida species were 15.30–46.40 μg/mL (25.91–78.60 μM) and 25.40–90.84 μg/mL (43.02–153.86 μM), respectively. In conclusion, P. pinnata possesses strong anti-Candida activity and its isolated compound, 6α-(3’-methoxy-4’-hydroxybenzoyl)-lup-20(29)-ene-3-one displayed potent anti-Candida and anti-biofilm action. These findings identify 6α-(3’-methoxy-4’-hydroxybenzoyl)-lup-20(29)-ene-3-one as a promising anti-Candida compound warranting further investigation, including cytotoxicity in mammalian cells, before its therapeutic potential can be fully assessed.

PLOS ONE

Prevalence of Congenital Heart Disease and Associated Factors among Infants with Myelomeningocele: A cross-sectional study

by Mohammed Nasir, Bereket Tessema, Sura Markos Background Meningomyelocele (MMC) is believed to commonly coexist with congenital heart disease (CHD), due to embryological pathways involving neural crest cells and risk factors such as folate and homocysteine metabolism abnormalities. However, evidence from developing countries is limited. Therefore, this study assessed the prevalence of CHD among infants with MMC and identified factors associated with the occurrence of CHD in infants with MMC. Methodology This hospital-based cross-sectional study was conducted at Hawassa University Comprehensive Hospital between May 1 and August 1, 2025. Infants with MMC born from January 1, 2018, to January 1, 2024, who underwent echocardiographic evaluation were included. Data were collected through chart review. Prevalence of CHD in infants with MMC was described using frequencies and percentages, and binary logistic regression identified factors associated with CHD. Results A total of 265 infants with MMC were included in this study. The prevalence of CHD among infants with MMC was 7.2%. The presence of maternal history of spontaneous abortion [AOR = 2.51, (95% CI: 1.12, 9.83); P = 0.03], maternal overweight or obesity [AOR = 2.93, (95% CI: 1.15, 7.98); P = 0.01], maternal diabetes mellitus [AOR = 2.22, (95% CI: 1.13, 8.45); P = 0.01], extracardiac anomalies in the infant [AOR = 2.94, (95% CI: 1.11, 8.78); P = 0.04] were associated with CHD in infants with MMC. Conclusion CHD was relatively common among infants with MMC, affecting 7.2% of cases. Factors associated with CHD included maternal history of spontaneous abortion, maternal overweight or obesity, maternal diabetes mellitus, and the presence of extracardiac anomalies in the infant. These findings highlight the significance of routine cardiac evaluation and targeted maternal risk assessment in infants with MMC to improve early detection and management.

PLOS ONE

Expression of Concern: Unraveling candidate genomic regions responsible for delayed leaf senescence in rice

by The PLOS One Editors

PLOS ONE

Expression of Concern: Genetic diversity and population structure of pigeonpea (<i>Cajanus cajan</i> [L.] Millspaugh) landraces grown in Benin revealed by Genotyping-By-Sequencing

by The PLOS One Editors

PLOS ONE

Expression of Concern: InDel markers: An extended marker resource for molecular breeding in chickpea

by The PLOS One Editors

PLOS ONE

Expression of Concern: Identification of stable heat tolerance QTLs using inter-specific recombinant inbred line population derived from GPF 2 and ILWC 292

by The PLOS One Editors

PLOS ONE

A comparative analysis of the performance of leading large language models on the endodontics section of the dentistry specialization exam in Türkiye

by Beyhan Başkan, Hatice Kübra Başkan, Nevzat Koç Objective This study aimed to evaluate and compare the performance of eight contemporary LLMs on the endodontics section of the DUS, assessing their accuracy in both theoretical knowledge and simulated clinical scenarios from historical exam data. Methods The performance of eight different large language models (Claude 4, DeepSeek V3, Gemini 2.5 Pro, ChatGPT-4o, ChatGPT-5, Grok 4, LLaMA 4, and Perplexity) was evaluated using 127 multiple-choice endodontics questions from the Specialization Exam in Dentistry (DUS) administered by the Student Selection and Placement Center (ÖSYM) between 2012 and 2021. The models’ responses were compared against the official answer keys. Statistical analyses were performed using Pearson’s chi-square and McNemar tests, with a significance level of α = 0.05. Results Significant differences existed among LLMs in overall accuracy (p  0.05). Conclusion Contemporary LLMs demonstrate substantial competence in endodontic knowledge, with Gemini 2.5 Pro excelling in both theoretical and clinical queries. However, significant performance variability across models (61.4%−90.6%) and the complexity of retrieving and resolving clinical exam queries necessitate domain-specific optimization and expert oversight for reliable integration into dental education and practice.

PLOS ONE

Phase angle is independently associated with muscle strength across multiple handgrip strength metrics in young adults: A cross-sectional study

by Juan Carlos Calderón-González, Luis Hebert Palma-Pulido, Gonzalo Romero-Martínez, Juan Carlos Urriago-Fontal, María Elisa Álvarez-Ossa, Frank Carrera-Gil, Robinson Ramírez-Vélez Objective Phase angle derived from bioelectrical impedance analysis has been proposed as a marker of muscle quality associated with muscle function; however, the extent to which its association with muscle strength is influenced by health status, dietary patterns, physical activity, and demographic factors remains incompletely characterized. This study examined the association between phase angle and muscle strength assessed using multiple handgrip strength (HGS) metrics, accounting for relevant clinical and lifestyle factors. Methods This cross-sectional study included 1,125 adults with complete data on phase angle, skeletal muscle mass, and HGS. Phase angle was measured using bioelectrical impedance analysis. Muscle strength was assessed as absolute HGS and HGS normalized to height² (HGS/h²). Low muscle strength was defined using sex- and age-specific international normative values below the 10th percentile for both HGS and HGS/height². Results Phase angle was consistently associated with muscle strength across both continuous and dichotomous analyses. In multivariable linear regression models, phase angle was positively associated with HGS (βstd = 0.26; P std = 0.38; P < 0.001). In logistic regression models, higher phase angle was associated with lower odds of low muscle strength (in fully adjusted Model 2 HGS: OR, 0.37; 95% CI, 0.29–0.48; HGS/h²: OR, 0.31; 95% CI, 0.24–0.41; both P < 0.001). These associations were independent of sex, age, body fat percentage, physical activity level, and comorbidity categories. Conclusions and relevance Phase angle was consistently associated with muscle strength across continuous and dichotomous outcomes after adjustment for adiposity, physical activity, and comorbidities. These findings suggest that phase angle may have potential utility as a supportive population-level marker in similar young adult populations; however, it should not be used as a substitute for direct muscle strength assessment at the individual level.

PLOS ONE

Bisphenol BPAF and BPC are agonists for estrogen receptor ERα but antagonists for N-terminal domain-lacking ERα

by Xiaohui Liu, Miki Shimohigashi, Yasuyuki Shimohigashi In the DNA complex of coactivator-bound estrogen receptor alpha (ERα), the N-terminal domain (NTD) and C-terminal ligand-binding domain (LBD) interact specifically. ERα-NTD and LBD constitute activation function 1 (AF-1) and activation function 2 (AF-2), respectively. We recently revealed that, despite the complete inactivity of ERα-NTD(AF-1), desNTD(AF-1)-ERα exhibited approximately 65% of the activity of the natural estrogen 17β-estradiol (E2) for wild-type full-length ERα. It remains unclear how a deficiency of NTD(AF-1) influences the activity of desNTD(AF-1)-ERα especially with respect to other estrogens and xenoestrogens. The major objective of this study is to evaluate the ligand specificity of desNTD(AF-1)-ERα for a series of xenoestrogens, including bisphenol A (BPA), BPAF, and BPC, together with E2, and the antagonists 4-hydroxytamoxifen (4-OHT) and ICI 182,780 (ICI). The receptors were transiently expressed in HeLa cells, and receptor activation activity was evaluated by luciferase reporter gene assay. Antagonist activity was examined for ERα and desNTD(AF-1)-ERα using E2 as a reference agonist. E2 exhibited full agonist activity for both ERα and desNTD(AF-1)-ERα, whereas 4-OHT and ICI were completely inactive and exhibited antagonist activity for E2 in both ERα and desNTD(AF-1)-ERα. All bisphenols were active for full-length ERα. Surprisingly, however, BPAF and BPC were almost completely inactive for desNTD(AF-1)-ERα, whereas BPA was fully active. BPAF and BPC exhibited distinct antagonist activity for E2 in desNTD(AF-1)-ERα, with pA2 values of 7.62 and 7.86, respectively. The present results revealed that the presence of the N-terminal NTD(AF-1) domain substantiates the agonist activity of halogen-containing BPAF and BPC in wild-type full-length ERα. ERα-NTD(AF-1) plays an essential role in determining the agonist/antagonist activity of BPAF and BPC for estrogen receptor ERα.

PLOS ONE

Types of genotypes in progressive familial intrahepatic cholestasis and liver transplantation: A meta-analysis of observational studies

by Rania Sakka, Hela Abroug, Sabrine Ben Youssef, Mongi Mekki, Ridha M’rad Background Progressive familial intrahepatic cholestasis (PFIC) refers to a group of inherited cholestatic liver diseases that affect children, often leading to liver failure and requiring liver transplantation (LT). Many studies have established correlations between the effect of the causal gene variant types and the severity of the PFIC phenotype, the treatment considered, or its outcomes in patients. Nevertheless, no selection criteria for LT based on genotypes have been adopted for patients affected by this group of diseases. Therefore, we conducted a meta-analysis to investigate the association between the main PFIC subtype genotypes and the treatment with LT. Methods Online databases were searched for articles on PFIC1–4 and LT. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. The genotypes of patients were extracted from the included studies and categorized into a group of cases, harboring null genotypes, and a group of controls, harboring non-null genotypes. The relationship between the genotype type and LT outcome was expressed as an OR by assessing the LT event among the case group and the control group. Results Eighteen studies involving 420 PFIC patients were included. A random-effects model was used to assess the OR. Overall, we observed a close relationship between the PFIC null genotype and the LT event; OR=2.79 (95% CI:1.63 to 4.77; p < 0.001). Subgroup analysis according to the PFIC subtype showed the same effect. Conclusions Our results provide evidence of a potential association between null genotypes in PFIC diseases and the indication of LT as a treatment. Further trials are needed to confirm our results and guide decisions regarding personalized and early preventive LT. Research protocol registration https://doi.org/10.17605/OSF.IO/MNQWB

PLOS ONE

Human versus AI in audiological practice: A comparative evaluation of ChatGPT and physician treatment decisions in idiopathic sudden sensorineural hearing loss

by Valeria Caragli, Michele Pellegrino, Luca Pingani, Gian Maria Galeazzi, Davide Soloperto, Elisabetta Genovese, Cosimo de Filippis, Gino Marioni, Leonardo Franz Purpose Artificial Intelligence (AI) is increasingly being applied in the field of audiology, demonstrating potential to support screening, diagnosis, and rehabilitation in auditory and vestibular disorders. However, its effectiveness in guiding complex therapeutic decisions—such as those for idiopathic sudden sensorineural hearing loss (ISSNHL)–remains uncertain. This study aimed to compare treatment recommendations for ISSNHL made by medical doctors (MDs) with those proposed by an AI system (ChatGPT, GPT-4o model). The goal was to evaluate the concordance between human and AI decision-making, particularly regarding the administration of corticosteroids and adjunctive therapies, and to assess AI’s potential in clinical practice. Methods This study is a retrospective observational analysis. Data from 86 patients diagnosed with ISSNHL were retrospectively analysed. Treatment decisions by MDs were compared with those generated by ChatGPT using anonymized patient datasets and a series of sequential prompts simulating multidisciplinary discussion. Agreement between AI and MDs was assessed using Cohen’s Kappa coefficient. Results Overall, poor to fair agreement was observed between AI and clinician treatment decisions. ChatGPT did not recommend oral corticosteroids in 26 cases where MDs prescribed them (Kappa = 0.029) and recommended intravenous corticosteroids in 20 patients who were not treated with this approach by MDs (Kappa = 0.393). Discrepancies were also evident in recommendations for intratympanic steroids (Kappa = −0.044) and adjunctive therapies (Kappa = 0.035). These differences likely stem from the AI’s rigid adherence to generalized treatment protocols and limited contextual understanding. Conclusion While ChatGPT (GPT-4o) shows promise in generating structured, protocol-driven suggestions, its clinical decision-making capabilities for ISSNHL remain inferior to those of experienced physicians. The AI’s lack of individualized reasoning and context sensitivity resulted in frequent discordance with physician-led care. Thus, AI should currently be viewed as a supportive tool in audiological practice, with its integration requiring careful oversight and further validation in real-world clinical environments.

PLOS ONE

Protocol for RETRO-TBI: A prospective cohort study of mild traumatic brain injury in older adults

by Jennifer S. Albrecht, Odessa Addison, Neeraj Badjatia, Mary K. Bahr-Robertson, Lynn M. Grattan, Ann L. Gruber-Baldini, Rosemary Kozar, Jay Magaziner, Denise L. Orwig, Michelle Newman, Deborah Stevens, Emerson M. Wickwire, Yuanyuan Liang Older adults experience the highest rates of traumatic brain injury (TBI) related hospitalizations and deaths of any age group, yet TBI remains understudied in this population. To improve understanding of recovery over the year following TBI among older adults, we designed the RETRO-TBI study. This manuscript reports the protocol for RETRO-TBI, a prospective cohort study of older adults (65 years and older) with mild TBI (mTBI) with planned enrollment of 250 participants. The study is designed to evaluate recovery across four key domains: physical function, cognitive function, psychological function, and sleep quality. Participants are followed for 12 months after injury, with in-home study visits conducted at approximately 2 weeks and 3, 6, and 12 months post-injury. Blood samples are collected at all visits. The specific aims are to: (1) identify trajectories of recovery in physical function and predictors of poorer physical recovery; (2) identify trajectories of recovery in cognitive function, psychological function, and sleep quality and predictors of poorer recovery in these domains; and (3) examine associations among recovery trajectories across domains. The RETRO-TBI study represents an important step in addressing the knowledge gap on recovery following TBI among older adults and is expected to result in identification of sub-groups of individuals more likely to have poor recovery, informing individualized treatment plans and development of future domain-based rehabilitation strategies. The study has several strengths including its focus on older adults, evaluation of recovery across four domains of function, and longitudinal assessments will permit evaluation of heterogeneity in recovery trajectories.

PLOS ONE

Interplay of the IGFBP-3 polymorphism and serum levels of IGF-1/IGFBP-3 with hormone receptor subtypes in patients with breast cancer among Palestinian women

by Heba Mohammed Arafat, Tengku Ahmad Damitri Al-Astani Tengku Din, Noorazliyana Shafii, Rosediani Muhamad, Ihab Naser, Nahed Al Laham, Ohood Mohammed Shamallakh Breast cancer remains a global public health challenge. This study aimed to investigate the relationships between serum levels of insulin-like growth factor binding protein 3 (IGFBP-3), insulin-like growth factor 1 (IGF-1), the IGFBP-3 A-202C polymorphism and hormone receptor subtypes: estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) with respect to breast cancer risk in Palestinian women. A cross-sectional study was conducted on 112 newly diagnosed, histopathologically confirmed breast cancer patients. Data collection included structured interviews and laboratory analyses, including biochemical, genetic, and immunohistochemical assessments. The tumor tissue samples were analyzed for ER, PR, and HER-2 status. SPSS version 28 was used for all data analysis. A high prevalence of hormone receptor positivity was observed. Among the breast cancer patients, 87.5% were ER positive and 84.8% were PR positive. A total of 75.9% were HER-2 negative. The IGFBP-3 A-202C genotype is significantly associated with PR and combined ER/PR positivity (p = 0.020). Patients with ER(+)/PR(+) status had significantly higher serum IGF-1 and IGFBP-3 levels (p ≤ 0.001), with IGF-1 levels positively correlated with hormone receptor status (rs = 0.232, p ≤ 0.001) and advanced disease stages, moderately with Stage III (rs = 0.191, p ≤ 0.001) and weakly correlated with Stage IV (rs = 0.119, p = 0.029). These findings suggest that IGF-1 and IGFBP-3 may have potential as candidate biomarkers for breast cancer risk and progression. Integrating genetic, biochemical, and hormone receptor status provides novel insights into breast cancer biology and may support future research on personalized prevention and treatment strategies, particularly in resource-limited settings such as the Gaza Strip.

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