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  • PLOS One

    https://journals.plos.org/plosone/

    Extensive intraoperative peritoneal lavage (EIPL) for gastric cancer with positive peritoneal lavage and/or stamp cytology: An exploratory phase II study

    by Gen Tsujio, Masakazu Yashiro, Yuichiro Miki, Kohei Matsuoka, Koji Maruo, Mami Yoshii, Tatsuro Tamura, Katsunobu Sakurai, Takahiro Toyokawa, Naoshi Kubo, Shigeru Lee, Tomohisa Okuno, Kishu Kitayama, Go Masuda, Masaichi Ohira, Kiyoshi Maeda

    Background

    Our group revealed that the combination of intra-operative stamp cytology and peritoneal lavage cytology (CY) improved the identification of individuals with high risk of peritoneal metastasis. In this exploratory Phase II study, we aimed to evaluate the effect on relapse-free survival (RFS) of extensive intraoperative peritoneal lavage (EIPL) for gastric cancer with positive peritoneal cytology (CY1) and/or stamp cytology positive (stamp+).

    Materials and methods

    This study was a single arm, multi-institutional, exploratory phase 2 trial to assess the effects of EIPL after open gastrectomy for gastric cancer with CY1 and/ or stamp+. The primary endpoint was RFS. Secondary endpoints were overall survival (OS), postoperative recurrence site and incidence of postoperative adverse events.

    Results

    Between 2017 and 2021, 13 patients from 2 institutions were enrolled in this study. Because of the recent decline in open abdominal surgery, the number of cases did not increase and the trial was closed due to lack of applicants at 13 cases. Median 3-year RFS was 14.5 months (95% CI 5.4-NA), median 3-year OS was not reached (95% CI 14.5-NA) and median3-year peritoneal RFS was 16.0 months (95% CI 5.4-NA). Median 3-year peritoneal RFS rate was 83% in CY0 and stamp+ cases (n=6), and 0% in CY1 and stamp+/- cases (n=7). (Log-rank p=0.015).

    Conclusion

    Because of the slow accrual pace and early stop of the trial, we were not able to evaluate the prespecified endpoints thoroughly. However, EIPL might be effective to prevent perineal recurrence, especially in CY0 and stamp+ case.


    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0347742

    Correction: Appropriate data segmentation improves speech encoding models: Analysis and simulation of electrophysiological recordings

    by Ole Bialas, Edmund C. Lalor


    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0347704

    Correction: Curated character of the Initial Upper Palaeolithic lithic artefact assemblages in Bacho Kiro Cave (Bulgaria)

    by Tsenka Tsanova, Vincent Delvigne, Svoboda Sirakova, Elka Anastasova, Pedro Horta, Ivaylo Krumov, João Marreiros, Elena Nacheva, Zeljko Rezek, Jean-Jacques Hublin, Nikolay Sirakov


    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0347680

    Treatment sequence patterns of urate-lowering therapy in Korean patients with gout: A common data model-based study

    by Min Jung Kim, Eun-Gee Park, Changyoung Kim, Dong Yoon Kang, Borim Ryu, Kichul Shin

    Background

    A treat-to-target strategy involving treatment modification improves outcomes in gout, but evidence remains limited regarding the optimal approach when initial urate-lowering therapy (ULT) fails. This study aimed to investigate real-world ULT sequence patterns and evaluate treatment retention based on the initial agent, modification type, and comorbidities.

    Method

    We analyzed electronic health record data collected from 2010 to 2022 from the common data model databases of two hospitals. Adults aged 18 years or older diagnosed with gout who initiated ULT and were followed for at least 2 years were included. Outcomes included the frequency and sequence of ULT prescriptions. Treatment modification, defined as switching to another ULT or adding an additional agent, was considered the end of retention for the previous regimen. Subgroup analyses were performed based on comorbidity.

    Results

    Among 2220 patients, febuxostat was the most common first-line agent (51.4%), with 90.9% maintaining therapy. Among those who modified febuxostat therapy, switchers and add-on users continued treatment similarly (91.5% vs. 86.8%, P = 0.33). Of allopurinol initiators, 55.8% changed therapy, mainly switching to febuxostat or benzbromarone rather than adding another agent (51.4% vs. 4.1%, P < 0.001), with similar retention rates (91.5% vs. 86.8%, P = 0.33). Among benzbromarone initiators, 57.2% changed therapy (switchers, 56.7%; add-on users, 0.5%; P < 0.001), and retention rates were 90.5% and 100%, respectively (P = 1.00). Chronic kidney disease was associated with low variability in ULT sequence.

    Conclusions

    ULT demonstrated durable retention when used as first- or second-line treatment, with switching being more common than add-on therapy and maintaining similar retention rates.


    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0347654

    Soluble ST2 as a biomarker for predicting severe adverse events among pediatric patients with Mycoplasma pneumoniae pneumonia

    by Fangying Cheng, Tingting Li, Lei Zhang, Menghua Xu, Luxi Chen, Zhicheng Ye, Jin Xu

    Aim

    Mycoplasma pneumoniae (MP) is a leading cause of pneumonia in children. Early identification of patients at high risk is critical for improving outcomes. This study aimed to evaluate the association of soluble ST2 (sST2) with in-hospital adverse events in pediatric MP pneumonia (MPP).

    Methods

    We retrospectively analyzed 147 children with MPP admitted to the Children’s Hospital of Fudan University, Shanghai, China, between 01/04/2023 and 31/05/2024. Demographic, clinical, and laboratory data were collected, including sST2, inflammatory markers (CRP, PCT, IL-6), and blood cell counts. Severe adverse events were defined as in-hospital death, ICU admission, diagnosis of sepsis or use of extracorporeal membrane oxygenation.

    Results

    Twelve patients experienced severe adverse events and had significantly higher sST2 levels. ROC analysis showed that sST2 predicted severe adverse events (AUC = 0.944, 95% CI 0.894–0.975, P < 0.001), with an optimal cut-off of 114.18 ng/mL (sensitivity 91.7%, specificity 94.8%). The association remained significant after adjusting for age, sex, PCT, and IL-6. In addition, admission sST2 levels were significantly higher in severe MPP cases, those with co-infections and those with pulmonary complications and/or extrapulmonary complications during hospitalization. sST2 correlated positively with hospital length of stay and preadmission fever duration. They also correlated positively with neutrophil counts, neutrophil to lymphocyte ratio, PCT, CRP and IL-6 but negatively with lymphocyte counts. Conclusions.sST2 was associated with in-hospital adverse events and it showed better performance in predicting severe adverse events than other inflammatory biomarkers. The potential of sST2 as a prognostic biomarker for MPP warrants further investigation.


    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0347651

    Correction: Geochemical signatures in plastic debris from the Curonian Lagoon, Lithuania

    by Sajjad Abbasi, Neda Hashemi, Patryk Oleszczuk, Viktorija Sabaliauskaitė, Nerijus Dzingelevičius, Arūnas Balčiūnas, Rita Vaičekauskaitė, Reda Dzingelevičienė


    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0347572

    Beyond the bamboo ceiling: How ethnic collaborative networks facilitate Chinese inventors’ knowledge remittances

    by Hua Zhang, Jia Liu, Chunhui Cao

    Previous research on the “bamboo ceiling” has focused on how ethnic homophily limits career advancement for East Asian immigrants. However, less is known about how their ethnic collaborative networks as U.S. Chinese immigrant inventors may facilitate knowledge remittances to their home countries. Drawing on social network theory, this study investigates two core network positions—centrality and structural holes (i.e., connecting otherwise unconnected co-inventors)—and their effects on knowledge remittances. Ethnic knowledge utilization serves as the mediator, while inventors’ past performance acts as the moderator. We test the proposed relationships using a unique dataset of patents in the integrated circuit industry. Results show that ethnic knowledge utilization mediates the relationship between network positions (centrality and structural holes) and knowledge remittance. Moreover, past performance significantly moderates the mediating paths: high-performing inventors more effectively exploit structural holes to facilitate knowledge remittance. They also strengthen the curvilinear effect of centrality, accelerating knowledge remittance at optimal centrality levels but triggering an earlier decline beyond these thresholds due to stronger path dependency. These findings not only support policies for leveraging diaspora knowledge networks but also advance the literature by establishing a more nuanced, attribute-based micro-foundation for understanding high-skilled migration’s impact on home-country development.

    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0347548

    Color outside the lines: How does amoral management influence employees’ creative unethicality?

    by Lei Ren, Yan Liu, Abdul Waheed Siyal, Xiaobin Zhang, Tianxing Pu

    Existing research has confirmed that amoral management can induce employees to engage in unethical behavior. However, its influence on a specific form of misconduct that involves creativity—namely, creative unethicality—remains unclear. Based on social information processing theory, this study constructs a theoretical model examining the influence of amoral management on employees’ creative unethicality. Through a three-stage investigation of 249 R&D employees from three intelligent manufacturing companies in eastern China, the results reveal that amoral management positively influences employee moral decoupling. Moral decoupling leads to creative unethicality under high job creativity requirements. Job creativity requirements moderates the indirect effect among amoral management, moral decoupling, and creative unethicality. Specifically, when jobs require high creativity, amoral management positively influences moral decoupling, thereby inducing creative unethicality. This study combines amoral management and creative unethicality, broadening the understanding of creative unethicality origins from the viewpoint of leaders’ moral conduct. It also provides empirical insights for organizations to manage creative unethicality through job stressors and leadership development.

    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0347530

    The clinical characteristics and risk factors of steroid-induced ocular hypertension following pars plana vitrectomy

    by Shuanghong Jiang, Hongxia Yang, Ting Chen, Zhenyu Ji, Xixi Yan

    Objective

    This study aimed to assess the incidence and risk factors for the development of steroid-induced ocular hypertension (SIOH) following 23-gauge (23G) pars plana vitrectomy.

    Methods

    The clinical data of patients treated with 23G vitrectomy from January 2019 to March 2022 were reviewed retrospectively. The incidence and characteristics of SIOH post-operatively and treatment provided were recorded. The clinical risk factors for developing SIOH were analyzed using logistic regression analysis.

    Results

    Among the 540 eligible patients, 111 (20.56%) cases developed SIOH. The majority (83.78%) of the SIOH cases developed between the third and seventh day postoperatively. Among these cases, 65 (58.56%) patients had an intraoperative pressure (IOP) of 30 mmHg or higher, and 31 (27.9%) had an IOP of 40 mmHg or higher. The IOP of all SIOH patients returned to normal within 1 month following the discontinuation of steroid and IOP-lowering medicine treatment. The independent risk factors for SIOH (IOP ≥ 23 mmHg) were myopia (odds ratio (OR) 5.22) and silicone oil filling (OR 8.20). For severe SIOH (IOP ≥ 30 mmHg) myopia and silicone oil filling were also identified as risk factors with an OR of 3.23 and 12.86, respectively. After adjusting the steroid administration pattern, the incidence of all SIOH and severe SIOH decreased to 17.11% and 9.14%, respectively.

    Conclusions

    Myopia and silicone oil filling were identified as potential independent risk factors for the development of SIOH after vitrectomy. A shorter topical steroid therapy was associated with a lower incidence of SIOH particularly in high-risk patients.


    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0347527

    A systematic review protocol: Efficacy and safety of nitrous oxide in analgesia in burn patients with dressing change

    by Weifeng Wang, Xianli Meng, Yan Zhao, Wei Gong, Xiaochen Jiang, Wenjuan Cao, Xueling Qiu, Chenxi Sun, Fan Sun, Yuchen Wang, Lu Tang

    Background

    To alleviate pain in burn patients during dressing changes, it is necessary to identify an effective analgesic method. Conventional opioid analgesics have many limitations. Nitrous oxide is a fast-acting, safe and reversible inhaled analgesic gas. This systematic review will evaluate the effectiveness and safety of nitrous oxide in the treatment of pain during dressing changes in burn patients.

    Method

    The protocol was developed according to the PRISMA-P checklist and registered on PROSPERO (CRD42024550197). A systematic search will be performed in the following databases: PubMed, EMBASE, Web of Science, Cochrane Library to identify clinical trials comparing nitrous oxide inhalation with standard care in pain management during dressing changes in burn wounds. The search of all databases will be conducted on October 15, 2025.Our search scope will include studies published between each database creation and search date.Two researchers will independently screen studies, extract data, and evaluate study quality using the Risk of Bias2 tool. Primary outcomes will include pain, anxiety, side effects, among others.R statistical software (version 4.3.1) and R studio will be used to perform meta-analyses.Effect size will be expressed by 95% confidence interval (Cl) of weighted mean difference (MD) and risk ratio (RR). Subgroup analyses and sensitivity analyses will be performed to explore sources of heterogeneity and assess the robustness of the results.Publication bias will be assessed using funnel plot and Egger test. We will use the Grading of Recommendation, Evaluation, Development and Evaluation (GRADE) to assess the quality of the evidence.

    Discussion

    Operative pain has always been a difficult problem for burn patients. This study will evaluate the analgesic effect of nitrous oxide on dressing change in burn patients through comprehensive search and rigorous methods, and provide evidence support for clinical decision-making.


    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0347524

    Utilization of the posterior iliac line for visualizing posterior column screws in obturator oblique view

    by Hongtao Li, Li Xu, Longxin An, Xiaojing Li, Linjing Zhang, Jun Liu, Kaili Zhai, Xuecheng Sun, Naibo Feng

    Purpose

    To evaluate whether posterior column screws penetrate the posterior cortical surface of the acetabulum when assessed using obturator oblique radiographic imaging.

    Methods

    Computed tomography (CT) scans were performed on the right acetabulum of 50 healthy adults to measure the angle (α) between the posterior wall of the acetabulum and the sagittal plane at the level of the femoral head’s maximal diameter. In addition, five cadaveric pelvises were subjected to C-arm fluoroscopic imaging. A 6 cm long, 1.5 mm Kirschner wire was positioned along the posterior surface of the acetabular posterior column, aligned with the greater sciatic notch, and imaged in both the 45° and α-degree obturator oblique views. The radiographic line visualized from the Kirschner wire in the obturator oblique view was defined as the posterior iliac line, and its anatomical relationship with the posterior surface of the posterior column was analyzed. Subsequently, a 2.5 mm Kirschner wire was inserted into the posterior column at the standard entry point for screw placement using an electric drill, with the wire tip intentionally positioned between the posterior iliac line and the posterior rim in the 45° obturator oblique view. The trajectory of the wire was assessed under both 45° and α-degree obturator oblique views to determine its relation to the osseous corridor.

    Results

    The measured angle between the posterior surface of the acetabular posterior column and the sagittal plane was (60.2 ± 2.5)°. In the 45° obturator oblique view, the posterior iliac line corresponded with the outer edge of the iliac crest superiorly and the outer edge of the ischium inferiorly, while the posterior wall was projected posterior to the midpoint of the posterior iliac line. In the α° obturator oblique view, the posterior iliac line maintained this alignment but intersected centrally with the posterior acetabular wall. The 2.5 mm Kirschner wire remained within the osseous corridor under the 45° view but potentially extended beyond it under the α° view.

    Conclusion

    When the posterior column screw is visualized posterior to the posterior iliac line in the 45° obturator oblique view, further assessment using a α° view is necessary. If the screw appears anterior to the posterior iliac line in the α° view, it indicates that the posterior cortical surface has not been breached.


    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0347522

    The complete mitochondrial genome of Holothuria atra (Holothuriida: Holothuriidae: Holothuria) and its structural characteristics

    by Jinjin Wang, Jianlong Ge, Meijie Liao, Bin Li, Xiaojun Rong, Yingeng Wang, Aijun Cui, Xiaodong Bian, Mingliang Sun, Qingyu Zhang

    Sea cucumbers, as typical representatives of deep-sea benthic animals, possess significant scientific and economic importance. This investigation examined the genomic structural characteristics and genetic evolutionary relationships of Holothuria atra through the analysis of its complete mitochondrial genome. The findings indicated that the total length of the mitochondrial genome of the H. atra specimen was 15,788 bp, encompassing seven NADH genes, three cox genes, two ATP genes, and one cob gene. Additionally, two rRNAs and 22 tRNAs were identified. The entire sequence contained a total of 18 non-coding regions and seven overlapping gene regions, with the combined A + T content reaching 59.2%. The lengths of the 22 tRNAs ranged from 62 to 72 base pairs, and their cloverleaf secondary structures were predicted. Regarding codon usage, the PCGs within the mitochondrial genome of H. atra utilized 61 codons, encoding information for 20 amino acids. The most abundantly encoded amino acid in the mitochondrial genome of H. atra is leucine (Leu), representing 16.58%, while cysteine (Cys) is the least represented, accounting for 1.03%. Codons with higher usage frequencies include AGA (Ser 1), CUA (Leu 1), and CCA (Pro), whereas those with comparatively lower frequencies are GCG (Ala), CCG (Pro), and AGG (Ser 1). Evolutionary analysis revealed that H. atra is most closely related to Holothuria polii. By comparing the mitochondrial genomic sequences of 19 species within the class Holothuroidea, it was observed that eight mitochondrial sequences are shared among these species. This study provides valuable data supporting genetic evolutionary research and the development and utilization of H. atra resources within the Kiribati region.

    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0347494

    Real-time torque behavior of reciprocating nickel–titanium instruments using different irrigating solutions

    by Uğur Dursun, Mevlüt Sinan Ocak

    Reciprocating nickel–titanium instruments generate mechanical stress during root canal preparation, which may affect instrument safety. Although instrument design is known to influence torque generation, the effect of different irrigating solutions on the real-time operative torque remains unclear. This study aimed to investigate the impact of various irrigating solutions on torque generated during root canal shaping using reciprocating single-file systems. Extracted human mandibular premolars with oval canals were assigned to groups prepared using sodium hypochlorite, ethylenediaminetetraacetic acid, or saline in combination with three reciprocating file systems. All canals were instrumented with a torque-controlled motor, and the real-time operative torque and preparation time were digitally recorded. The mean torque, maximum torque, and shaping duration were statistically compared between the irrigant and instrument groups. The irrigation solution alone did not show a significant main effect on torque values or preparation time. However, a significant interaction between the file system and irrigant type was detected, indicating that the torque response depended on the specific file–irrigant combination. In contrast, the file system type significantly influenced torque behavior, with the T-Endo MUST system producing higher mean and peak torque than the other instruments. These findings suggest that instrument design characteristics may have a greater impact on the development of mechanical stress during root canal preparation than the irrigation solution used.

    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0347424

    Study on the mechanical behavior and fracturing mechanism of rock containing two unparallel prefabricated fissures under uniaxial loading

    by Jian Li, Yunyun Wei, Tie Wang

    As a natural material, rock is widely used in construction and building engineering, such as wall brick and road foundations. However, natural rock usually contains fissures and fractures, which greatly affect the long-term structural stability. In this paper, the mechanical behavior and fracturing mechanism of red sandstone containing two unparallel prefabricated fissures under uniaxial loading are studied using the finite-discrete element method (FDEM), and the modeling results are compared with the experimental results. Firstly, the uniaxial compression tests on the intact red sandstone are conducted to calibrate the input parameters in FDEM, which are validated against experimental stress-strain curves and failure modes. Then, a series of uniaxial compression numerical models of rock samples containing two fissures with different angles (β2) of the second fissure are established. Finally, the influence of β2 on the stress-strain curve, crack number and acoustic emission (AE) characteristics, failure mode, stress and displacement fields and energy evolution during uniaxial compression is discussed. Results indicate that the uniaxial compressive strength (UCS), peak strain and Young’s modulus all increase first and then decrease with the increase of β2. Especially, these indexes have a maximum value when β2 = 90°, and have the smallest value with a β2 of 180°. The material exhibits progressive failure characteristics when β2 = 180° based on AE singles but brittle failure is dominant in other cases. Generally, shear failure is concentrated at the fissure tips, while tensile failure mainly occurs in the complete zone inside the specimen. Besides, the evolution of peak strain energy with β2 is the same as the changing trend of the above indexes, but the kinetic energy shows a decreasing trend as β2 increases. The stress and displacement fields before cracking can well explain the crack propagation and intersection mechanism. The simulated failure mode and crack morphology reproduce most of the phenomena observed in the laboratory test. The results in this paper provide theoretical support for the design of deformation and bearing capacity of fractured red sandstone-based projects such as fractured rock mass tunnel.

    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0347408

    Identification and detection of genetic markers associated with antimicrobial susceptibility and evaluation of efflux pump mechanisms in Mycoplasma iowae

    by Dominika Buni, Áron Botond Kovács, Enikő Wehmann, Dénes Grózner, Krisztián Bányai, Eszter Zsófia Nagy, Janet Bradbury, Marco Bottinelli, Elisabetta Stefani, Salvatore Catania, Inna Lysnyansky, László Kovács, Miklós Gyuranecz, Zsuzsa Kreizinger

    Mycoplasma iowae is an economically significant pathogen that causes reduced hatchability, late embryo mortality and leg deformities, chondrodystrophy and skeletal lesions in poults. While prevention is essential in the control of infection, the appropriate administration of antibiotics may reduce economic losses during outbreaks. As a first step in the exploration of antimicrobial resistance mechanisms in M. iowae, target modification and efflux pump activity were examined in the present study. Point mutations were analyzed in previously described antibiotic binding sites in the whole genome sequences of 99 M. iowae strains. Mismatch amplification mutation assays (MAMAs) were designed and validated for the differentiation of mutations corresponding to elevated minimum inhibitory concentration (MIC) values for fluoroquinolones. Broth microdilution assays were performed to evaluate the effect of efflux pump inhibitors. In the presence of orthovanadate (OV), MIC values were significantly lower than in the absence of OV for spiramycin, tilmicosin, tylosin and oxytetracycline, which may indicate the presence of an active efflux system in M. iowae. Putative promoter regions of efflux-related genes were predicted and characterized. Genetic mutations, previously described in other bacteria, were described to be associated with elevated fluoroquinolone, macrolide and lincomycin MICs in M. iowae, although certain resistant phenotypes remained unexplained, promoting future examinations for deeper insights. The developed MAMAs may support rapid identification of M. iowae strains with elevated MIC values for fluoroquinolones. The better understanding of the efflux pump mechanisms enables the development of alternative methods for the support of therapy against this pathogen.

    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0347345

    Comfort in a cross-sector care delivery model to address birth inequities: Learnings from San Francisco’s Pregnancy Village

    by Osamuedeme J. Odiase, April J. Bell, Alison M. El Ayadi, KaSelah Crockett, Malini A. Nijagal, Patience A. Afulani

    Introduction

    Comfort is a key factor in physical and mental health, influencing overall well-being. Though once seen as peripheral to the patient care experience, it is now recognized as a critical outcome. For Black and other historically minoritized birthing individuals—who face racism, disproportionally higher morbidities, and unequal care—comfort is key to a safe, positive pregnancy experience. Innovative, community-driven models designed to improve comfort are therefore needed. San Francisco’s Pregnancy Village (PV) is a novel, cross-sector care delivery model providing a one-stop shop for clinical, city government, and wraparound services in a dignified and uplifting environment for Black and other minoritized pregnant individuals and their families. This study aims to examine comfort at PV and its key predictors.

    Methods

    We surveyed 114 participants (57 pregnant/postpartum individuals and 57 family members) between July 10, 2021 and June 30, 2022. Comfort was measured using a 3-item scale capturing the affective dimension of comfort, with scores standardized to 0–100 scale. Additionally, two individual items assessed situational aspects of comfort: (1) discomfort being seen at PV and (2) feeling out of place at PV. We performed univariate, bivariate, and multivariate analyses.

    Results

    The mean comfort score was 96.2/100 (SD = 11.4). Pregnant and postpartum participants, as well as those with limited social support, felt significantly less comfortable with the idea of being seen by friends at PV compared to family members and those with strong social support, respectively. Participants with some higher education and those reporting occasional everyday discrimination felt significantly less out of place at PV than those with a high school diploma or no discrimination experiences.

    Conclusions

    The Pregnancy Village model fostered generally high levels of comfort among Black and other minoritized pregnant individuals and their families in San Francisco, California. However, lower comfort levels among pregnant and postpartum individuals, those with lower educational attainment, and individuals lacking social support underscore the need for greater investment in co-led community-institutional, culturally responsive, and trauma-informed care approaches to foster comfort, particularly for those who face the severest inequities.


    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0347316

    Evaluation of the predictive accuracy of QUICKI and McAuley indices for insulin resistance in adolescents: Insights from a cross-sectional study

    by Miriam Mohatar-Barba, Ángel Fernández-Aparicio, Javier S. Perona, Jacqueline Schmidt-RioValle, Carmen Enrique-Mirón, Emilio González-Jiménez

    Different indirect methods have been developed to assess insulin resistance (IR), though their validation has been limited to adult populations. In this sense, the study aim is to compare the predictive capacity of the McAuley, QUICKI, SPISE indices, and glucose-insulin ratio against insulin resistance (IR) in Spanish adolescents and to establish reliable cut-off values for these indices in this population. A cross-sectional study was conducted with 981 adolescents aged 11–16 years, from Southern Spain. Anthropometric measurements and fasting biochemical parameters, were assessed. IR indices, such as HOMA-IR, QUICKI, the McAuley index, SPISE, and the glucose-insulin ratio, were calculated. The ability of each index to predict IR was evaluated using multivariate regression analysis and receiver operating characteristic (ROC) curves. Boys exhibited higher waist circumference, triglyceride levels, and fasting insulin levels, while girls had a higher percentage of body fat (p < 0.05). HOMA-IR values increased in adolescents with obesity, whereas McAuley and QUICKI indices decreased significantly (p < 0.05). Similar results were found in adolescents with MetS in comparison to non-MetS adolescents. QUICKI showed the highest predictive accuracy (AUC: 1.00), followed by the McAuley index (AUC: 0.983 in boys, 0.977 in girls), and SPISE (AUC: 0.896 in boys, 0.852 in girls). The cut-off points for these indices were 5.794,0.316, and 7.8 respectively, both for boys and girls. The glucose-insulin ratio demonstrated poor predictive ability. The QUICKI, McAuley, and SPISE indices are effective in predicting IR among Spanish adolescents. Their use could aid in early detection of metabolic and cardiovascular disfunctions, though further validation in larger cohorts is required for clinical application.

    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0347304

    Complications and mortality following percutaneous and laparoscopic liver biopsy: A multicenter study in a resource‑limited healthcare system

    by Nadieh Abdallah, Ahed Almahdi, Diana Shella, Rasha Al-Masri, Iyad Maqboul, Mohammad Jaber, Ramzi Shawahna

    This study was conducted to assess the incidence and types of complications and mortality following liver biopsy, and to identify independently associated factors that can inform clinical practice in a resource‑limited healthcare system. A retrospective multicenter study was conducted across six major hospitals between January 2020 and December 2025. Medical records of 218 patients undergoing percutaneous and laparoscopic liver biopsies were reviewed. Demographic, clinical, laboratory, procedural, and outcome variables were extracted using a validated data collection form. Inferential analyses were conducted using chi‑square, Fisher’s exact, and Mann‑Whitney U tests, while multivariate logistic regression models were employed to identify factors independently associated with complications and mortality. The most common types of complications were infection (n = 7, 3.2%) and hemorrhage (n = 6, 2.8%), followed by pulmonary complications (n = 4, 1.8%), metabolic disturbances (n = 3, 1.4%), and acute kidney injury (n = 2, 0.9%). Mortality was recorded in 6 patients (2.8%). Higher pre-operative white blood cell count was independently associated with infections (OR: 1.28, 95% CI: 1.02–1.62, p = 0.036). Older age was independently associated with mortality (OR: 1.07 per year increase, 95% CI: 1.01–1.15, p = 0.035). Hemorrhage and pulmonary complications were more frequent after laparoscopic biopsy and under general anesthesia, although these associations did not remain significant in adjusted models. This study provides the first systematic evidence on liver biopsy safety in Palestine, a resource‑limited healthcare system, thereby filling a critical gap in the regional literature. The study identified pre-operative increases in white blood cell count as a predictor of infection and older age as a predictor of mortality. These simple, pragmatic markers can guide monitoring and risk stratification in constrained environments, offering actionable insights for clinicians and policymakers. Future studies should be conducted to evaluate whether these markers can help reduce complications and mortality.

    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0347300

    Survival status and predictors of mortality among preterm neonates admitted to the neonatal intensive care unit at public hospitals of Harari region and Dire Dawa administration, eastern Ethiopia: Retrospective cohort study 2025

    by Boru Abera Ebsa, Maleda Tefera, Dawit Tamiru, Abraham Negash, Naol Oda, Merga Dheresa

    Background

    The neonatal period is the most vulnerable time for an infant’s survival, particularly for preterm neonates. Preterm birth is among the leading causes of neonatal mortality. Many neonatal complications can be prevented, but preterm birth remains a leading cause of admission, death, and long-term complications, highlighting the need for further research on outcome and survival disparities across populations and settings. Therefore, this study aimed to assess survival status and predictors of mortality among preterm neonates admitted to neonatal intensive care units at public hospitals in the Harari region and Dire Dawa administration, Eastern Ethiopia, from November 1, 2021 to October 30, 2024.

    Methods

    The hospital-based retrospective cohort study was conducted among preterm neonates admitted to the neonatal intensive care unit at public hospitals of the Harari region and Dire Dawa administration, Eastern Ethiopia. A simple random sampling technique was used, and data were extracted from neonates’ medical records and registration formats using a structured checklist prepared in English. Descriptive statistics, life table, Kaplan-Meier curves, and Log-rank test were used to estimate and compare survival time. Predictors of mortality were identified using the Cox Proportional Hazard model.

    Results

    Out of 612 preterm neonates, 205 (33.5%; 95% CI: 29.76–37.39) died, corresponding to an incidence rate of 52.76 deaths per 1,000 preterm neonate-days (95% CI: 46.01–60.50), with a median survival time of 18 days. As multivariable cox-regression result,  ≥ 4 antenatal care contact (AHR = 0.56; 95% CI: 0.36–0.89), receiving KMC (AHR = 0.16; 95% CI: 0.09–0.27), 5th minute APGAR score <7 (AHR = 1.80; 95% CI: 1.22–2.66), PNA (AHR = 1.55; 95 CI: 1.08–2.22), resuscitation with bag and mask at birth (AHR = 1.59; 95% CI: 1.10–2.29), RDS (AHR = 1.75; 95% CI: 1.22–2.51), born in non-cephalic presentation (AHR = 1.68; 95% CI: 1.12–2.53), and neonatal sepsis (AHR = 1.58; 95% CI: 1.09–2.28) were identified as significant predictors of preterm neonates mortality.

    Conclusion

    The incidence of preterm neonatal mortality was high in this study. Adequate Antenatal care (ANC) and kangaroo mother care (KMC) significantly improved preterm survival, while low APGAR score, resuscitation with bag and mask, neonatal sepsis, PNA, and RDS were major predictors of preterm neonatal death. Emphasis should be placed on strengthening antenatal and perinatal care, along with early detection and management of identified neonatal complications.


    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0347244

    A pyroptosis-related gene signature for the diagnosis of acute pancreatitis

    by Yuting Wang, Jun Li, Zhongsu Yu, Shuyuan Li, Yuxia Chen, Yun Pan, Liangping Cheng, Guangyuan Yu

    Acute pancreatitis (AP) is a severe inflammatory disorder in which pyroptosis—a pro-inflammatory form of programmed cell death—may contribute to pathogenesis. However, the complete transcriptional profile of pyroptosis-related genes (PRGs) in AP and their potential as diagnostic biomarkers remain underexplored. This study aimed to systematically characterize pyroptosis-associated transcriptional signatures and identify the reliable biomarkers for diagnostic purposes. Three transcriptomic datasets from murine AP models were integrated to identify pyroptosis-related differentially expressed genes (PRDEGs). Functional enrichment and immune cell infiltration analyses were conducted to elucidate the biological pathways and immune microenvironment alterations associated with these genes. mRNA-transcription factor (TF) and mRNA-microRNA (miRNA) regulatory networks were constructed to investigate underlying molecular interactions. Machine learning techniques, including support vector machine (SVM) and least absolute shrinkage and selection operator (LASSO), were applied for feature selection, leading to the identification of key diagnostic markers and the development of a logistic regression model. The regression model were then assessed using an independent cohort of human peripheral blood samples. Eleven PRDEGs were identified, with enrichment observed in processes such as cytoskeletal organization, cell-substrate adhesion, and critical inflammatory signaling pathways, including MAPK and NF-κB. Immune infiltration analysis revealed significant correlations between these PRDEGs and various immune cell subsets, particularly M1 macrophages, Treg cells, and monocytes. A four-gene diagnostic signature, comprising ANXA3, IQGAP1, RELA, and VTN, was established through SVM and LASSO analysis. In the independent human cohort, the fixed-coefficient four-gene model demonstrated reduced discrimination, which likely reflects interspecies and tissue-specific variations. However, after optimizing the model to exclude non-significant predictors, a refined two-gene signature (ANXA3 and IQGAP1) exhibited improved accuracy, with excellent calibration and clinical net benefit. This study offers a comprehensive transcriptomic analysis of the pyroptosis-mediated landscape and immune microenvironment in AP. An optimized two-gene signature, comprising ANXA3 and IQGAP1, was validated in a human cohort with superior accuracy, reflecting critical disruptions in inflammatory pathways and cytoskeletal organization. Notably, ANXA3 demonstrated potential for stratifying disease severity. Although these markers hold potential for molecular diagnosis, further prospective studies are essential to establish their clinical specificity and generalizability across diverse populations.

    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0347204

    Sucralose inhibited cell survival through the activation of ER stress in human endothelial progenitor cells

    by Chia-Ying Li, Hung-Yu Lin, En-Pei Isabel Chiang, Hung-Chang Hung, Feng-Yao Tang

    Sucralose, a widely utilized non-caloric sweetener, is frequently added to food and beverage products as a sugar substitute aimed at lowering energy consumption and reducing obesity-related health risks. However, epidemiological studies have indicated a possible association between high intake of sucralose and increased prevalence of coronary artery disease (CAD). Prior research has demonstrated that diminished levels of circulating human endothelial progenitor cells (hEPCs) are linked to a higher risk of CAD. Although sucralose is broadly consumed, its direct biological impact on hEPCs has not been comprehensively characterized. In this study, we investigated the cellular effects of sucralose on hEPCs using a variety of in vitro techniques, including assays for viability, migration, capillary-like tube formation, lactate dehydrogenase (LDH) release-cytotoxicity assay, and protein expression profiling by Western blotting. Our results revealed that increased concentrations of sucralose significantly impaired hEPCs viability, motility, and neovasculogenic function, accompanied by increased expression of markers associated with apoptosis, inflammasome activation, and pyroptosis. Mechanistic analysis further demonstrated that sucralose strongly activated endoplasmic reticulum (ER) stress/PERK pathways in these cells. Inhibition of ER stress via 4-phenylbutyric acid (4-PBA) substantially attenuated sucralose-induced cell death and reduced the expression of pyroptosis-related proteins and inflammasome markers. Taken together, these findings suggest that sucralose disrupts hEPCs function in part by triggering ER stress, which promotes both apoptotic and pyroptotic cell death programs.

    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0347149

    Effects of salinity and broad-range antibiotics on oxalate production, transport, and degradation in Poecilia latipinna

    by Felicia Vimala Rajan, Carol Bucking

    Oxalate is an anion that readily binds calcium and is thought to contribute to osmoregulation. This study investigated how environmental salinity influences oxalate homeostasis in euryhaline sailfin mollies (Poecilia latipinna), with a focus on the interplay between microbial symbiosis and host transport processes. Gut microbiome profiling demonstrated regional specialization, with the posterior intestine enriched in oxalate-degrading bacterial families. Community shifts across salinities suggests functional redundancy and resilience, ensuring maintenance of oxalate-catabolizing capacity. Antibiotic treatment disrupted this system, impairing microbial degradation and causing systemic oxalate stress. Oxalate concentrations were also measured in the liver, intestine, and kidney, organs central to oxalate metabolism, under freshwater and seawater conditions. Salinity induced a redistribution of oxalate among these organs, with the gut assuming an auxiliary excretory role in seawater. This functional shift parallels mammalian colon physiology and highlights the gut’s role in balancing ion and oxalate flux. Expression analyses of the oxalate transporters SLC26A3 (solute carrier family 26, member 3) and SLC26A6 (solute carrier family 26, member 6) revealed organ-specific and salinity-dependent regulation. Both transporters displayed distinct responses to seawater exposure, indicating specialized roles in oxalate handling. These patterns suggest coordinated but nonredundant mechanisms that govern absorption and secretion, linking salt transport with oxalate clearance. These findings underscore the microbial contribution to oxalate balance and reveal that osmoregulatory challenges shape gut microbial composition and function. Collectively, this study presents the first comprehensive analysis of oxalate metabolism in a euryhaline teleost and demonstrates a coordinated host–microbe system that mitigates oxalate accumulation across salinities. By integrating metabolic and osmoregulatory demands, P. latipinna reallocates excretory function from kidney to gut and leverages microbial symbiosis to preserve homeostasis. These findings expand our understanding of teleost physiology and highlight oxalate metabolism as a critical axis of environmental adaptation.

    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0347147

    Dysregulated lactate metabolism synergizes with ALS genetic risk factors to accelerate motor decline

    by Shweta Tendulkar, Tong Wu, Amy Strickland, Amber R. Hackett, Yurie Sato-Yamada, Xianrong Mao, Yo Sasaki, Jeffrey Milbrandt, A. Joseph Bloom, Aaron DiAntonio

    Neurons rely on glial ‘lactate shuttling’ for metabolic support, which declines with aging and in neurodegenerative disease. Full disruption of lactate shuttling in peripheral nerves causes progressive axon degeneration, but we were interested to understand how partial disruption, a scenario more relevant to aging and disease, contributes to neurodegeneration risk. Pyruvate and lactate are interconverted by lactate dehydrogenases (LDHA and LDHB) in both lactate producing and consuming cells. We therefore began by investigating Ldhb knockout mice (loss of LDHA, the dominant LDH in liver and muscle, caused embryonic lethality), and discovered that they develop progressive neuromuscular junction atrophy and functional decline without axon degeneration. Because even Ldhb+/- heterozygosity significantly affects motor behavior, we also wondered about a potential link to congenital disease and pursued this by identifying rare loss-of-function LDHB variants among ALS patients. Next, to better understand how LDHB loss leads to motor decline, we selectively deleted it in defined cell types. Schwann cell (SC)-specific deletion caused robust motor defects, whereas motor neuron–specific deletion has little effect. Reasoning that neuronal LDHB deficiency could model age-associated decline in lactate metabolism, we asked whether it would interact with ALS genetic risk. Indeed, motor-neuron LDHB deficiency synergizes with relatively mild ALS risk variants— TDP43Q331K and Sod1D83G knock-in alleles—to produce early motor neuropathy, indicating that LDHB loss enhances disease risk. These findings establish lactate metabolism as a modifier of motor system vulnerability and highlight it as a therapeutic target in peripheral as well as central neurodegeneration.

    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0347135

    Distinct plasma cytokine and chemokine profiles in severe COVID-19 and septic shock

    by Se Ju Lee, Jaehoon Kim, Min Han, Jung Ah Lee, Yongseop Lee, Jung Ho Kim, Jin Young Ahn, Su Jin Jeong, Nam Su Ku, Joon-Sup Yeom, Jun Yong Choi

    Background

    Severe Coronavirus Disease 2019 (COVID-19) and septic shock are both characterized by dysregulated host immune responses. While similarities and differences in immune responses between COVID-19 and bacterial sepsis have been reported, direct comparative analyses remain limited. This study aims to characterize the immunologic status of patients with COVID-19 and sepsis through plasma cytokine/chemokine analysis, thereby providing additional candidates for immunomodulatory therapy for COVID-19.

    Methods

    We included patients diagnosed with severe COVID-19 or septic shock with lymphopenia, matched for age, sex, steroid administration, and severity. A total of 20 analytes were measured using Luminex assay.

    Results

    A total of 36 patients were enrolled. Plasma granulocyte-macrophage colony-stimulating factor (GM-CSF) concentrations were significantly higher in the COVID-19 group (5.3 pg/ml; IQR, 3.6–16.3 vs 0.0 pg/ml; IQR, 0.0–3.6; P = 0.010). Plasma interleukin-10 (IL-10) (0.0 pg/ml; IQR, 0.0–4.8 vs 28.8 pg/ml; IQR, 7.5–51.7; P = 0.003) and IL-15 (0.0 pg/ml; IQR, 0.0–0.0 vs 0.0 pg/ml; IQR, 0.0–5.6; P = 0.024) levels were significantly higher in the sepsis group. Firth logistic regression analysis showed that plasma IL-6, IL-8, and CXCL16 levels were associated with new organ support in the sepsis group, while IL-15, CXCL16, and IL-1RA levels tended to be associated in the COVID-19 group.

    Conclusion

    At day 7 after diagnosis, both groups exhibited active proinflammatory responses, but only the sepsis group showed prominent anti-inflammatory responses. The persistent elevation of GM-CSF in the COVID-19 group, even with steroid administration, highlights its potential as a therapeutic target and underscores the need for patient stratification in immunomodulatory trials.


    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0347126

    Self-efficacy and self-regulated learning strategies as significant predictors of english writing proficiency in Chinese EFL senior high school students

    by Xiaoli Chen, Jingxia Yan, Wenxiu Guo

    Self-efficacy and self-regulated learning strategies are crucial importance for enhancing the writing proficiency of foreign language learners. This study employed a cross-sectional design to examine the relationships among writing self-efficacy, writing self-regulated learning strategies and writing proficiency in Chinese senior high school students learning English as a foreign language (EFL). A convenience sample of 223 participants completed a writing test and two adapted questionnaires: the Questionnaire of English Writing Self-Efficacy (QEWSE) and the Questionnaire of English Writing SRL Strategies (QEWSRLS). Both instruments were adapted the participants’ actual situation and showed good reliability and validity. Students’ writing proficiency was assessed based on essays scored by two independent raters. Correlation analysis was used to examine the relationships between these constructs and writing performance, and confirmatory factor analysis (CFA) was conducted to establish and validate the measurement models. The results showed significant positive relationships between the constructs, indicating that higher levels of self-efficacy and greater use of SRL strategies are associated with better writing performance. There is robust construct validity for both measurement models: a five-dimensional model of writing self-efficacy (RMSEA = 0.030) and a nine-dimensional model of writing SRL strategies (RMSEA = 0.027). These findings underscore the importance of integrating psychological and strategic factors into pedagogical practices to enhance EFL writing instruction in similar contexts.

    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0347121

    AI literacy among basic school teachers in Ghana: A structural equation modelling analysis

    by Valentina Arkorful, Francis Arthur, Ernest Opoku, Ayishatu Ameen, Iddrisu Salifu, Sharon Abam Nortey, Solomon Adjatey Tetteh

    Understanding the synergy of Artificial Intelligence (AI) literacy among teachers is imperative for successful integration in educational settings. This study examined basic school teachers’ (BSTs) AI literacy based on four key aspects: AI knowledge and understanding (KUAI), AI application (AAI), AI application evaluation (EAIA), and AI ethics (AIE). The study employed a cross-sectional survey design and purposive sampling to collect data from 319 BSTs in Ghana. A variance-based structural equation modelling (VB-SEM) approach was used to explore the relationships between these dimensions and provide insights into their interrelationships. The study found that AAI positively influenced KUAI, EAIA, and AIE. However, AIE did not significantly influence KUAI and EAAI. In addition, KUAI did not influence EAIA. The findings contribute to understanding the current state of AI literacy among BSTs in Ghana and highlight areas for improvement in AI education and professional development programmes.

    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0347117

    A tripartite multifactorial analysis of abstract anaphoric choice between this and this+NP in Chinese L2 English argumentative writing: Extending the usage-based approach to discourse alternation

    by Jianwei Xu, Ming Yue, Yujing Yang

    The usage-based approach has documented L2 learners’ general convergence with native speakers in the probabilistic constraint patterns governing syntactic alternations. However, whether this convergence pattern extends to discourse-level phenomena remains an open question. This study addresses this gap by examining the abstract anaphoric alternation between this and this+NP (reduced vs. explicit form) in argumentative writing. We analyze a dataset of 1,304 instances from L2 students (Mandarin Chinese-L1) and 1,303 instances from a native English baseline. Each instance was annotated for four discourse-internal factors—givenness, antecedent type, subjectness, and distance—operationalizing the economy-clarity trade-off of accessibility theory. A tripartite multifactorial analysis—examining constraint significance, ranking, and interactions—was conducted within each of three sequential phases: first, establishing an L1 baseline model; second, independently characterizing the L2 system; and third, conducting a direct statistical comparison. Results indicate that: (1) L1 choices are systematically constrained by multiple probabilistic competing factors; (2) when analyzed independently, L2 learners show sensitivity to the same core constraints, constraint hierarchy, and fundamental interaction logic as native speakers; and (3) statistical comparison confirms broad convergence, with the only reliable divergence localized to a single context: L2 learners overuse the explicit this+NP in the highest-accessibility topic-continuity context. These findings demonstrate that L2 learners exhibit largely the same fundamental constraint system that guides native speakers’ choices, extending the scope of usage-based explanations from syntactic alternations to discourse-level phenomena in second language research.

    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0347116

    Carbon footprint assessment and crashworthiness evaluation of alloy steel W-beam guardrails

    by Shuai Gong, Wendong Fan, Haoze Zhao, Zhihao Zhang, Shuming Yan

    In response to the dual demands of enhancing safety and greening transportation infrastructure under China’s “Dual Carbon” goals, this study overcomes the limitations of traditional guardrail materials and processes by proposing and validating a synergistic pathway for optimizing both the safety and carbon emission reduction of alloy steel corrugated beam guardrails. A systematic “material design – process optimization – performance verification – environmental assessment” framework was established. High-performance 700L-grade alloy steel was produced through low-carbon alloy design combined with ESP short-process rolling technology. Its safety performance was quantitatively evaluated via SB-level full-scale vehicle crash tests, and its life-cycle carbon footprint was quantified using an ISO 14067-compliant model implemented in eFootprint software with the CLCD database. The results demonstrate that the alloy steel achieves a synergistic optimization of strength and plasticity, with a tensile strength of 766–781 MPa and a product of strength and elongation (PSE) exceeding 0.175 GPa·%. In the full-scale vehicle crash tests, all occupant risk indicators were superior to the safety limits. For instance, the key risk parameters for the small passenger car, such as the longitudinal velocity (Vx = 4.3 m/s) and the lateral acceleration (ay = 126.0 m/s²), demonstrated excellent performance. The maximum dynamic outward inclination equivalent values for the medium and large trucks were 1.75 m and 2.45 m, respectively. These results confirm that the safety performance of the guardrail fully meets the SB-level standard, even with a lightweight design featuring a 25% reduction in beam thickness and a 50% reduction in post thickness. Life-cycle analysis revealed that the carbon footprint per kilometer of guardrail was reduced to 80.86 t CO2e, representing a 73.8% reduction compared to the conventional solution. Sensitivity analysis identified iron input and electricity consumption as the core influencing parameters. Furthermore, a cost-benefit analysis indicated superior life-cycle cost advantages. This study elucidates the mechanism for achieving synergistic gains in safety and emission reduction through material and process innovation, providing a systematic solution and data support for the green, low-carbon, and safe transformation of highway infrastructure.

    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0347115

    The intrinsic structure and interrelations of tea culture constructed from tea-related toponym texts: Evidence from China

    by Yiru Xu, Rong Wang, Hongqi Wu

    Tea culture is an important part of the regional culture and intangible cultural heritage that is valued and favored worldwide. The connotations of tea culture are mapped and precipitated in toponyms, which significantly influence the naming and renaming of said toponyms. However, rigorous research integrating tea culture and geographical naming systems is still premature, with a robust analytical framework yet to be established. This study explores China’s Hunan Province as the main research area, adopts the grounded theory method to explore the connotations of tea culture in tea-related toponym texts, and examines in depth the structure of tea culture as well as its internal relationships. The study notes that the more profound the tea culture, the more tea-related toponyms. Evidently, tea culture and toponyms are related. The results show that, on the one hand, the structure of tea culture can be deconstructed into six elements, namely tea tree, tea custom, tea industry, tea activity, tea polity, and tea shape. The structural inheritance and development of tea culture are the result of the interaction of various elements. On the other hand, tea culture’s internal structure comprises two interactive unit systems. From the overall-unit perspective, the natural environment and cultural atmosphere interact. The tea tree is the core of the natural environment, while the cultural atmosphere is jointly created by tea custom, tea industry, tea activity, tea polity, and tea shape. From the perspective of internal structural units, the six elements of tea culture’s structure interact to form an “effect-feedback” mutual influence pattern. This study systematically elucidates the structure of tea culture and interactions between its constituent elements. Such an analysis is crucial for a deeper understanding of local tea culture’s structural inheritance mechanisms. This study provides theoretical support and practical guidance for the development of tea-related industries.

    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0347109

    Unguided web-based brief intervention with genetic risk education to reduce unhealthy alcohol consumption in Japan: Protocol for a randomized controlled trial

    by Yuki Kono, Mai Tanaka-Sahker, Shino Kikuchi, Yan Luo, Masatsugu Sakata, Ryuhei So, Tamara L. Wall, Toshi A. Furukawa, Ethan Sahker

    Background

    Alcohol consumption is a major global contributor to morbidity and mortality and is a well-established risk factor for multiple cancers. Acetaldehyde, a toxic metabolite of ethanol, is a causal factor in alcohol-related esophageal cancer. A substantial proportion of the Japanese population carries the aldehyde dehydrogenase 2*2 (ALDH2*2) allele, which impairs ALDH2 enzymatic activity and increases acetaldehyde exposure, thereby elevating esophageal cancer risk. Among individuals with the ALDH2*2 allele, cancer risk demonstrates a clear dose–response relationship with alcohol consumption, with relative risks reported to be up to four times the relative risk, compared to non-carriers.

    Objectives

    This project aims to evaluate the efficacy of an unguided, web-based brief intervention (BI) incorporating genetic cancer-risk education to reduce alcohol consumption in a randomized controlled trial.

    Methods

    Participants will be recruited online between March and July 2026 through a Japanese research panel company. Eligibility will include moderate alcohol use and probable ALDH2*2 allele status. Participants will be randomized to either an experimental condition or a sham educational control. The experimental group will receive an unguided, web-based, brief video intervention providing information on genetic cancer risks associated with alcohol consumption and the benefits of reducing drinking. The primary outcome will be mean past-4-week alcohol quantity at the 3-month endpoint. Secondary outcomes will include alcohol use in grams, alcohol-related severity, motivation to change, health-knowledge retention, participant satisfaction, and quality of life. Assessments will occur at baseline and at 1, 2, and 3 months post-randomization via a secure web portal.

    Discussion

    This intervention is expected to reduce unhealthy alcohol use at low implementation cost by leveraging personalized genetic risk information as a motivational mechanism in the general population. Additional between-group differences are anticipated across secondary alcohol-related outcomes.Trial Registration: This trial registered on 11/28/2025 in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000058012).


    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0347064