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Correction: Hepatic transcript profiling in beef cattle: Effects of rumen-protected niacin supplementation

PLoS ONE Jan 16, 2025 DOI: 10.1371/journal.pone.0317922

Advancing biomonitoring of eDNA studies with the Anaconda R package: Integrating soil and One Health perspectives in the face of evolving traditional agriculture practices

PLoS ONE Pierre-Louis Stenger, Audrey Léopold, Kelly Dinh et al. Jan 16, 2025 DOI: 10.1371/journal.pone.0311986

Soil health and One Health are global concerns, necessitating the development of refined indicators for effective monitoring. In response, we present the Anaconda R Package, a novel tool designed to enhance the analysis of eDNA data for biomonitoring purposes. Employing a combination of different approaches, this package allows for a comprehensive investigation of species abundance and community composition under diverse conditions. This study applied the Anaconda package to examine the impact of two types of duration fire-fallow cropping systems, using natural forests as a reference, on soil fungal and bacterial communities in Maré Island (New Caledonia). Condition-specific taxa were identified, particularly pathogenic fungi and bacteria, demonstrating the importance of long-term fallowing efforts. Notably, this package also revealed the potential contributions of beneficial soil microbes, including saprophytes and plant-endophyte fungi, in suppressing soil-borne pathogens. Over-represented microbial ASVs associated with both plant and animal pathogens, including those of potential concern for human health, were identified. This underscores the importance of maintaining intrinsic balance for effective disease suppression. Importantly, the advanced analytical and statistical methods offered by this package should be harnessed to comprehensively investigate the effects of agricultural practice changes on soil health within the One Health framework. Looking ahead, the application of this method extends beyond the realm of One Health, offering valuable insights into various ecological scenarios. Its versatility holds promise for elucidating complex interactions and dynamics within ecosystems. By leveraging this tool, researchers can explore the broader implications of agricultural practice modifications, facilitating informed decisions and sustainable environmental management.

RETRACTED: Synergistic development of intangible cultural heritage and tourism industry: Empirical experiences from Jilin, China

PLoS ONE Jing Lv, Yuanlu Chai, Xinyue Hu Jan 16, 2025 DOI: 10.1371/journal.pone.0313421

This study focuses on the Jilin region of China, conducting a multidimensional assessment of the current state of the synergistic development between Intangible Cultural Heritage (ICH) and the tourism industry in the area. The objective is to explore the issues surrounding the coordinated development of ICH and the tourism sector. The findings are as follows: 1) The overall coupling degree between the ICH and tourism systems in the Jilin region is 0.7851, with 91.99% of the indicators falling within the high correlation range and 8.01% within the very high correlation range, indicating a strong coupling effect between the two systems; 2) Structural coupling analysis shows that the coupling degree is highest in Changchun City and weakest in Baicheng City. In Changchun, the proportions of indicators in Quadrant I (maintain current status) are 50%, 50%, and 54.84%, respectively, while in Baicheng, the proportions in Quadrant II (priority improvement) reach 50%, 63.5%, and 47.5%, respectively; 3) Dynamic coupling analysis reveals that from 2008 to 2022, the ICH and tourism systems in the Jilin region exhibited a trend of coordinated development. This study not only confirms the synergistic relationship between ICH and the tourism industry, enriching theoretical research in this field, but also provides practical guidance for other regions seeking to achieve coordinated development between ICH and tourism, thereby holding significant practical value.

Running trends in Switzerland from 1999 to 2019: An exploratory observational study

PLoS ONE Anja Witthöft, Thimo Marcin, Mabliny Thuany et al. Jan 16, 2025 DOI: 10.1371/journal.pone.0311268

Background Several single race events (5 km, 10 km, half-marathon, marathon, ultra-marathon) in different countries and different years have been analyzed in multiple studies, representing the rising interest in endurance-based activity and thus physical health. With focus on participation numbers, performance or sex difference, many single study results were obtained. The running trends in a whole country covering a longer period of time and several race distances are missing so far. Objectives The aim of this study is therefore to examine 5 km, 10 km, half-marathon, marathon and ultra-marathon races by age, sex, participation numbers and performance during two decades (1999–2019) for one country (Switzerland). Methods In this exploratory observational study, we analyzed 1,172,836 finishers (370,517 women and 802,319 men) competing between 1999 and 2019 in 5 different race distances in Switzerland. We used publicly available data about the athletes and examined total finishing numbers, sex, age and performances (measured in m/s) via descriptive analyses and linear mixed models. Do-not-finishers were excluded. Results The most frequented race was the half-marathon (33.1% of finishers), the less frequented was the ultra-marathon distance (8.5% of finishers). In most recent years, only the number of finishers in ultra-marathon, especially in trail runs increased. In total, there were more male finishers (68.4%) than female finishers (31.6%) and only in 5 km races, more women finished than men (55.3%). Men were faster than women and both sexes were running slower in all race distances across years. Athletes in 10 km races had the best performance within the five analyzed race distances. Median age increased with longer race distance and decreased in ultra-marathon in recent years. Conclusion In summary, finishing numbers especially in ultra-marathons increased with a focus on trail runs, female and male athletes had a declining performance across years in all race distances and men ran faster than women. Median age increased with longer race distance leading to more aged endurance-trained athletes. A downtrend in median age is found only in ultra-marathon in recent years. The results are important for athletes, race directors and coaches with regard to training schedules and the trend towards long distance races as well as for the medical attendance especially of older athletes, being more and more interested in endurance running.

Stochastic variation in foraging traits within inbred lines of Drosophila

PLoS ONE Kaiya Hamamichi, Yuma Takahashi Jan 16, 2025 DOI: 10.1371/journal.pone.0289864

Investigating the causes and consequences of niche partitioning in populations is a major goal in ecology and evolutionary biology. Previous studies have investigated genetic and environmentally induced variation in resource utility and their ecological implications. However, few studies have explored variability (non-genetic, stochastic variation) as a factor contributing to variation in resource utility. In this study, we studied the variability in foraging traits of Drosophila lutescens, a species of wild fruit fly. Using 70 iso-female lines from a single population, we observed two foraging traits, i.e., locomotive speed and resource preferences, in an “8”-shaped experimental arena containing different types of fruit juices. The mean locomotive speed and relative preference for orange juice over grape juice varied significantly among iso-female lines. Additionally, the degree of intraline variation (variability) was detected a fold-change of larger than 2-fold between the smallest line and the largest line. While the mean locomotive speed itself did not correlate with mean resource preferences, the variability of locomotive speed significantly correlated with that of resource preferences. These results suggest that the degree of variability within inbred lines for both locomotive activity and resource preference is potentially partly genetic and that a shared genetic basis may govern variability in these traits. The variability of a particular trait is considered to interact cooperatively with the variability of several other traits in creating phenotypic intraspecific variation within a population.

Two-dimensional non-Hermitian skin effect in an ultracold Fermi gas

Nature Entong Zhao, Zhiyuan Wang, Chengdong He et al. Jan 16, 2025 DOI: 10.1038/s41586-024-08347-3

Preventive and curative dental services utilization among children aged 12 years and younger in Tehran, Iran, based on the Andersen behavioral model: A generalized structural equation modeling

PLoS ONE Elaheh Amirian, Samaneh Razeghi, Alireza Molaei et al. Jan 16, 2025 DOI: 10.1371/journal.pone.0312043

World Health Organization invites the nations to progress towards universal health care coverage. This study evaluated preventive and curative dental services utilization among children aged 12 years and younger in Tehran, Iran, based on the Andersen behavioral model using a generalized structural equation modeling. A phone-based cross-sectional study was conducted in Tehran, Iran, on 886 children in 2023. Information on curative and preventive/consultation dental service utilization and associated factors was collected by a standard questionnaire. We used a generalized structural equation model (GSEM) to build a model based on Andersen’s behavioral model. Of 886 children, 22.1% used curative dental services, and 19.9% used preventive/consultation services in the past year. Among children aged 6 years and younger, age (OR = 1.87, p-value <0.001) and parent-perceived oral health need (OR = 54.77, p-value <0.001) predicted curative services utilization and age (OR = 1.45, p-value <0.001), knowledge (OR = 1.36, p-value <0.001), dental visit before the age of one (OR = 6.05, p-value = 0.04), and socioeconomic status (OR = 1.65, p-value = 0.03) predicted preventive/consultation services utilization. Regarding children aged 7 to 12, knowledge (OR = 1.28, p-value = 0.03), dental visit before the age of one (OR = 11.12, p-value = 0.02), socioeconomic status (OR = 2.53, p-value = 0.01), dental insurance (OR = 4.17, p-value <0.001), and parent-perceived oral health need (OR = 19.48, p-value <0.001) associated with curative dental services utilization, and dental visit before the age of one (OR = 10.05, p-value = 0.02), oral health behavior (OR = 1.25, p-value = 0.04), socioeconomic status (OR = 3.74, p-value <0.001), and parent-perceived oral health need (OR = 4.62, p-value <0.001) related to preventive/consultation services utilization. The findings of this study underscore the significant influence of predisposing, enabling, and need factors on dental services utilization among children aged 12 years and younger. These results provide a valuable perspective for policymakers, highlighting the modifiable determinants that could be targeted to improve dental services utilization in this age group.

Exploring mental health symptoms in elite athletes during the COVID-19 pandemic: A systematic review and meta-analysis on sex differences

PLoS ONE Liang-Tseng Kuo, Sung-Huang Laurent Tsai, Udit Dave et al. Jan 16, 2025 DOI: 10.1371/journal.pone.0314996

The COVID-19 pandemic significantly affected elite athletes, leading to increased mental health issues such as stress, anxiety, and depression. Sex differences in mental health may exist among athletes during the COVID-19 crisis. This study aimed to perform a systematic review and meta-analysis to examine sex differences in mental health symptoms among elite athletes during the COVID-19 pandemic. We systematically searched the databases including Pubmed, EMBASE, and manually checked previous systematic reviews for relevant studies in March 2024. Authors were also contacted for sex-specific data. Studies were included if they compared mental health symptoms between male and female elite athletes during the COVID-19 pandemic. We used a random-effects model to summarize the rate ratio (RR) between female and male athletes across studies. Risk of bias in studies was assessed using a 9-item tool. We included 18 studies in this review. The results indicated that female athletes reported higher levels of anxiety (RR 1.24, 95% CI = 1.08 to 1.43) and depression (RR 1.36, 95% CI = 1.15 to 1.61) than male athletes during the pandemic. They also had a higher risk of stress or distress (RR 1.27, 95% CI = 0.99 to 1.63) than their male counterparts. No significant differences were found regarding alcohol use or misuse between female and male athletes (RR 1.01, 95% CI = 0.75 to 1.37). Limited evidence was available for eating disorders, gambling, substance use, and sleep problems. In conclusion, female and male athletes differed in mental health symptoms during the COVID-19 pandemic. Female athletes were more likely to report anxiety, depression, and distress. Incorporating mental health resources may be particularly important for women’s sports, which have smaller financial margins and greater career uncertainty than men’s sports.

Long-term excessive salt consumption alters villous and crypt morphology and the protein expression of uroguanylin, TRPV6 and PMCA1b in the rat small intestine

PLoS ONE Natchayaporn Thonapan, Kannikar Wongdee, Sirion Aksornthong et al. Jan 16, 2025 DOI: 10.1371/journal.pone.0317415

Although long-term high dietary sodium consumption often aggravates hypertension and bone loss, sodium in the intestinal lumen has been known to promote absorption of nutrients and other ions, e.g., glucose and calcium. However, whether high-salt diet (HSD) altered mucosal morphology, villous cell turnover and calcium transporter expression remained elusive. Herein, rats were treated with HSD containing 8% wt/wt NaCl for up to 5 months. HSD rats exhibited a marked increase in sodium intake with high fecal and urinary sodium excretion, as compared to the control group treated with normal diet. Intestinal histomorphometry revealed increasing of crypt depth and villous height in 3- and 4-month HSD groups, respectively, consistent with larger mucosal-to-serosal amplification ratio that reflected an increased surface area for nutrient absorption. The signals of Ki-67-positive cells was enhanced in the crypts as visualized by multiphoton fluorescence microscopy, whereas the TUNEL-positive cells were decreased in the villi of HSD, suggesting greater crypt cell proliferation and a reduction of villous cell apoptosis. Confocal microscopy showed higher expression of TRPV6 protein in the villous tip of HSD, while PMCA1 expression was increased in villous tip and crypt areas. The percentage of cells with highly expressed uroguanylin—an endogenous intestinal natriuretic peptide—was significantly higher in HSD group. In conclusion, HSD profoundly changed the intestinal morphology and turnover of epithelial cell, increased the expression of calcium transporters and uroguanylin. Our findings reflect pathophysiological adaptations in the intestine, which might be another target organ for drug discovery against HSD-induced osteopathy in the future.

Half logistic exponentiated inverse Rayleigh distribution: Properties and application to life time data

PLoS ONE Juma Salehe Kamnge, Manoj Chacko Jan 16, 2025 DOI: 10.1371/journal.pone.0310681

This paper presents a novel extension of the exponentiated inverse Rayleigh distribution called the half-logistic exponentiated inverse Rayleigh distribution. This extension improves the flexibility of the distribution for modeling lifetime data for both monotonic and non-monotonic hazard rates. The statistical properties of the half-logistic exponentiated inverse Rayleigh distribution, such as the quantiles, moments, reliability, and hazard function, are examined. In particular, we provide several techniques to estimate the half-logistic exponentiated inverse Rayleigh distribution parameters: weighted least squares, Cramér-Von Mises, maximum likelihood, maximum product spacings and ordinary least squares methods. Moreover, numerical simulations were performed to evaluate these estimation methods for both small and large samples through Monte Carlo simulations, and the finding reveals that the maximum likelihood estimation was the best among all estimation methods since it comprises small mean square error compared to other estimation methods. We employ real-world lifetime data to demonstrate the performance of the newly generated distribution compared to other distributions through practical application. The results show that the half-logistic exponentiated inverse Rayleigh distribution performs better than alternative versions of the Rayleigh distributions.

β-C−H bond functionalization of ketones and esters by cationic Pd complexes

Nature Yi-Hao Li, Nikita Chekshin, Yilin Lu et al. Jan 16, 2025 DOI: 10.1038/s41586-024-08281-4

Multidimensional vulnerability and financial risk protection in health in contexts of protracted conflict: Evidence from the Occupied Palestinian Territory

PLoS ONE Julia Hatamyar, Sally Shayeb, Akseer Hussain et al. Jan 16, 2025 DOI: 10.1371/journal.pone.0314852

This paper proposes a multidimensional vulnerability index for a setting of protracted conflict, which is applied to study the relationship between financial vulnerability and catastrophic healthcare expenditure (CHE) incidence in the Occupied Palestinian Territory in 2018. We find that our index better captures the extent of financial risk protection in health compared to conventional measures of financial welfare. Results indicate that the most vulnerable groups experience a significantly higher likelihood of incurring CHE, and this likelihood is increased for those living in the West Bank compared to the Gaza Strip. We also find a lack of protection from existing health insurance types against the risk of CHE. Our analysis provides valuable insights about key aspects, such as health financing and insurance bottlenecks, that will deserve careful policy attention in efforts to rebuild the Palestinian health system, following the Israel-Hamas war.

Pasteurized waste milk vs. milk replacer at the same crude protein:metabolizable energy ratio with different energy sources (fat vs. lactose) to pre-weaning Holstein calves: Effects on growth performance, feeding behavior, and health

PLoS ONE Shahryar Kargar, Borhan Moradi, Meysam Kanani et al. Jan 16, 2025 DOI: 10.1371/journal.pone.0317405

The improved growth performance of calves at weaning results from an effective pre-weaning feeding strategy. The type and pasteurization process of liquid feed are among the most variable feeding practices affecting calves’ growth and health. In previous studies that compared waste milk (WM) vs. milk replacer (MR), little consideration has been given to the variations in chemical composition and feeding behavior between them, and there has been a lack of justification for the crude protein: metabolizable energy (CP:ME) ratio adopted. Hence, this study aimed to evaluate the effects of feeding pasteurized WM or MR differing in energy source (fat vs. lactose, respectively) with similar CP:ME ratio on intake, growth, feeding behavior, and health of newborn Holstein calves. Thirty-two male calves (4-d-old; 40.0 ± 0.58 kg BW) were assigned to the trial and randomly allocated to each liquid feed diet (WM or MR). Calves were housed in individual pens with free access to starter feed and fresh water. Calves were weaned on d 61 and assessed until d 101 as the postweaning period. WM-fed calves had greater total nutrient intake (DM, CP, EE, and ME), weight gain, final BW, skeletal growth parameters, and feed efficiency (d 30). Calves WM-fed sorted less against particles retained on the 2.36-mm sieve but more against particles retained on the sieve of 0.6 mm. In WM-fed calves, the sorting index decreased for feedstuff retaining on the bottom pan compared with MR-fed calves. Irrespective of the type of the liquid feed, all calves sorted for particles retaining on the sieve of 4.75 mm and the bottom pan, and against the particles that were retained on the sieves of 2.36- (MR-fed calves only), 1.18- and 0.6-mm. Starter feed nutrient intake and particle size intake from the sieves of 4.75-, 2.36-, and 1.18-mm increased in WM- vs. MR-fed calves. Eating rate and meal size but not meal frequency and length were greater in WM-fed calves, leading to higher pre- and post-weaning starter feed intake. Calves WM-fed spent less time eating and standing but more time ruminating and lying than MR-fed calves. Calves WM-fed had a lower likelihood of having elevated general appearance (score ≥2; hazard ratio = 2.79), diarrhea (score ≥3; hazard ratio = 1.35), and pneumonia (hazard ratio = 4.77). Calves WM-fed experienced shorter days with elevated general appearance, diarrhea, and pneumonia. Overall, feeding WM led to increased starter feed intake by boosting the eating rate and meal size, promoting greater growth than MR. Additionally, compared with MR, WM feeding increased time spent ruminating and lying and reduced susceptibility to diarrhea and pneumonia.

A qualitative study to understand the facilitators of and barriers to retention in care to the national PMTCT Option B+ programme in Uganda

PLoS ONE Charity Kyomugisha-Nuwagaba, Rachel King, Rose Baryamutuma et al. Jan 16, 2025 DOI: 10.1371/journal.pone.0314885

Introduction Effective prevention of mother to child transmission (PMTCT) programmes require women and their infants to have access to a cascade of HIV care and treatment interventions. Retention in care reduces the risk of vertical transmission and opportunistic infections among mothers living with HIV. Uganda has made great strides in ensuring the success of the prevention of mother to child transmission program. Although an increasing number of people living with HIV (PLHIV) in Uganda are benefiting from the rapid scale-up of antiretroviral therapy (ART), retention in HIV care and treatment services remains a major concern. Identifying and understanding the reasons for dropping out of care among mothers enrolled in the Option B+ program among those who were retained and those who dropped out is key to inform policy and program practice. Methods We conducted a qualitative study to understand the facilitators of retention and reasons for loss to follow-up among HIV positive mothers in central Uganda who engaged in the Option B+ program. We conducted 29 focus group discussions (FGDs) with Village Health Teams (VHT) and ‘Peer Mothers’. We performed 21 in depth interviews (IDI) with mothers who had been lost to follow up during the post-partum period, and 27 among those who remained in care. These were conducted in 18 districts in Central Uganda. Results Participants identified barriers and facilitators to retention in HIV care. Barriers included self-stigma and fear of disclosure, mental health challenges, community perceptions, poor health provider attitudes and structural challenges, lack of transportation and food, long waiting time at health facilities and client mobility. Both the clients retained and not retained in care discussed mental illness, feeling sick and competing priorities as barriers. Facilitators for retention in care included adequate community support systems, early initiation on ART, giving birth to HIV negative children and economic stability. These were noted as key enabling factors for retention. It was also highlighted that presence of friendly clinic staff members, scheduling reminders were important aspects of retention. Conclusion Findings highlighting barriers covering personal, interpersonal, structural and community suggest that developing client-centered models addressing social and community barriers and provide more holistic services is key to retaining mother-infant pairs in care. Emphasis on the use of community health workers and provision of financing, as well as institutionalization of quality improvement would provide alternatives for overcoming barriers to retention in care.

1-Methylxanthine enhances memory and neurotransmitter levels

PLoS ONE Ralf Jäger, Sidney Abou Sawan, Marco Orrù et al. Jan 16, 2025 DOI: 10.1371/journal.pone.0313486

1-Methylxanthine (1-MX) is the major metabolite of caffeine and paraxanthine and might contribute to their activity. 1-MX is an adenosine receptor antagonist and increases the release and survivability of neurotransmitters; however, no study has addressed the potential physiological effects of 1-MX ingestion. The aim of this study was to compare the effect of 1-MX on memory and related biomarkers in rats compared to control. Memory (escape latency in the Morris water maze test), neurotransmitters (acetylcholine, dopamine, gamma-amino butyric acid (GABA)), and neurochemicals (BDNF, catalase, glutathione, Amyloid Beta and cyclic GMP) were analyzed from whole brain samples in young (8-weeks-old) and aged (16-months-old) rats following 12 days of supplementation (100 mg/d HED of 1-MX [UPLEVEL®, Ingenious Ingredients L.P., Lewisville, TX, USA]) via oral gavage. 1-MX supplementation reduced escape latency by 39% in young animals and 27% in aged animals compared to controls (both p<0.001). Additionally, 1-MX increased the levels of acetylcholine, dopamine, GABA, and cyclic GMP (all p<0.001). Furthermore, 1-MX supplementation led to reduced amyloid beta and higher catalase, BDNF and glutathione concentrations (p<0.001). Collectively, our findings suggest that 1-MX may have cognitive-enhancing and neuroprotective properties.

DomeVR: Immersive virtual reality for primates and rodents

PLoS ONE Katharine A. Shapcott, Marvin Weigand, Mina Glukhova et al. Jan 16, 2025 DOI: 10.1371/journal.pone.0308848

Immersive virtual reality (VR) environments are a powerful tool to explore cognitive processes ranging from memory and navigation to visual processing and decision making—and to do so in a naturalistic yet controlled setting. As such, they have been employed across different species, and by a diverse range of research groups. Unfortunately, designing and implementing behavioral tasks in such environments often proves complicated. To tackle this challenge, we created DomeVR, an immersive VR environment built using Unreal Engine 4 (UE4). UE4 is a powerful game engine supporting photo-realistic graphics and containing a visual scripting language designed for use by non-programmers. As a result, virtual environments are easily created using drag-and-drop elements. DomeVR aims to make these features accessible to neuroscience experiments. This includes a logging and synchronization system to solve timing uncertainties inherent in UE4; an interactive GUI for scientists to observe subjects during experiments and adjust task parameters on the fly, and a dome projection system for full task immersion in non-human subjects. These key features are modular and can easily be added individually into other UE4 projects. Finally, we present proof-of-principle data highlighting the functionality of DomeVR in three different species: human, macaque and mouse.

Dual intent view contrastive learning for knowledge aware recommender systems

Scientific Reports Jianhua Guo, Zhixiang Yin, Shuyang Feng et al. Jan 16, 2025 DOI: 10.1038/s41598-025-86416-x

Physical and biological properties of a novel anti-adhesive punctate uneven gelatin film

PLoS ONE Yuki Ozamoto, Tsunehito Horii, Shinichiro Morita et al. Jan 16, 2025 DOI: 10.1371/journal.pone.0314159

Since abdominal adhesion are quite problematic in abdominal and pelvic surgery, the conventional HA/CMC film are commonly used as an anti-adhesive material. However, such types are difficult to be rolled and delivered through the port of laparoscopic surgical devices due to adherence to the laparoscopic port or other parts of the films. To create an anti-adhesion film with more favorable handling properties and anti-adhesive effect, we developed a novel punctate uneven gelatin film (PU GF). In this study, we examined the physical strength, flexibilities and adhesiveness between film to tissues or film each other, compared to the conventional film and the flat gelatin film (Flat GF). In addition, we investigated the cell proliferation on each film and the anti-adhesive effect of the films and those reattachment possibility using a rat cecum abrasion model. The PU GF showed excellent tensile strength, ductility, and adherence to tissue compared to Flat GF and the conventional film. Moreover, the adherence of PU GF to the other film and to a silicon sheet were much lower than those of the Flat GF and conventional film. The proliferation of cells in PU GF and Flat GF were suppressed compared with control, though increased with time. The anti-adhesive scores of the PU GF after one time and re-attachment were significantly higher than that of non-covered control, although there was no significant difference between that of the conventional film and control. Our findings suggest that PU GF improve handling properties of laparoscopic surgery as it has excellent physical strength, ductility, and adherence to tissue, and low adherence to trocar. In addition, the punctate film may be more useful with the re-attachability without tearing and to retained sufficient anti-adhesion effect.

A spherical vector-based adaptive evolutionary particle swarm optimization for UAV path planning under threat conditions

Scientific Reports Yanfei Liu, Hao Zhang, Hao Zheng et al. Jan 16, 2025 DOI: 10.1038/s41598-025-85912-4

Distinct immunological features of oropharyngeal cancer peritumoral tonsillar tissues from inflammatory tonsils and regional lymph nodes: A pilot study

PLoS ONE Naohiro Wakisaka, Makiko Moriyama-Kita, Satoru Kondo et al. Jan 16, 2025 DOI: 10.1371/journal.pone.0316102

Background Cancer immune responses are generated in secondary lymphoid organs, such as the lymph nodes and tonsils. In the current study, transcriptional profiles of peritumoral tonsillar tissues (PTTs) from oropharyngeal cancers (OPCs) were assessed and compared with those of inflammatory tonsils and regional lymph nodes (rLNs). Methods RNA samples of PTTs and rLNs from 13 OPCs, and 4 inflammatory tonsils were subjected to microarray analysis, and differentially expressed genes (DEGs) identified from 730 nCounter Panel immune-related genes. Gene Set enrichment Analysis (GSEA) was used for DEG profiling of PTTs and rLNs between lymph node metastasis-negative and metastasis-positive cases. The top 20 genes, as ranked by GSEA metric scores, were extracted and subjected to principal component analysis (PCA). The correlation of each patient’s PCA score with lymph node status was assessed by Receiver Operating Characteristics (ROC) analysis. Results Comparing DEG analyses of PTTs with those of inflammatory tonsils and rLNs revealed 144 and 45 upregulated genes, respectively. ClueGO, a widely used Cytoscape plug-in, revealed activated pathways in PTTs, including lymphocyte proliferation (followed by T cell activation involved in the immune response) and positive regulation of leukocyte migration (followed by antimicrobial humoral immune response mediated by antimicrobial peptides) as the most significantly enriched immune system process functions in the gene ontology when comparing inflammatory tonsils and rLNs. The area under the ROC curves of PTTs and rLNs were 0.806 and 0.389, and were significant by DeLong’s test (p = 0.025). Conclusion PTTs exhibit unique immunological features distinguishing them from inflammatory tonsils and rLNs. Gene expression analysis of PTTs is useful for investigating the mechanism of OPC lymphatic spread, even compared with analysis of rLNs.