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전체arXiv CS.AI6,534arXiv Math6,523arXiv Physics2,314arXiv Stat1,122PLOS ONE423arXiv Q-Bio318arXiv Econ316PLOS Global Public Health61PLOS Biology24PLOS Medicine14
PLOS ONE

Association of leuko-glycemic index with mortality in ICU patients with Acute kidney injury: A retrospective multicenter cohort study

by Xuejin Ye, Sheng Chen, Lin Guo, Xiaohan Ma, Lingling Wu, Yiwen Li, Ting Zhang, Peng Jiang, Hongjun Gao Background Acute kidney injury (AKI) complicates the course of critical illness and carries high short- and long-term mortality rates; however, reliable early prognostic markers remain limited. The leuko-glycemic index (LGI), the product of white blood cell counts and blood glucose, has shown prognostic value in other acute conditions; however, its role in intensive care unit (ICU) patients with AKI remains unexplored. Methods In this multicenter retrospective cohort study, we analyzed 112,235 adult ICU admissions from the MIMIC-IV (n = 54,840) and eICU-CRD (n = 57,395) databases. Patients with multiple ICU stays and those aged <18 years were excluded. The LGI was calculated within 24 h of admission and stratified into quartiles (Q1–Q4). The primary endpoints were 30- and 90-day in-hospital mortality, and the secondary endpoint was overall in-hospital mortality. Kaplan–Meier survival curves, multivariable Cox proportional hazards models, and restricted cubic splines (RCS) assess the association between LGI and outcomes, with subgroup and interaction analyses for key comorbidities. Results Higher LGI quartiles were associated with progressively worse survival (p < 0.0001). In the fully adjusted models, each unit increase in LGI conferred a small but significant rise in 30-day (HR 1.01; 95% CI 1.01–1.01) and 90-day mortality (HR 1.01; 95% CI 1.01–1.01), while Q4 versus Q1 yielded HRs of 1.22 (95% CI 1.13–1.31) and 1.21 (95% CI 1.13–1.30), respectively. RCS demonstrated a nonlinear relationship, and the associations persisted across subgroups. Conclusion LGI may be an independent biomarker associated with short-term mortality in ICU patients with AKI. Its potential clinical relevance warrants further investigation and validation in larger cohorts.

PLOS ONE

Preschool and primary school teachers’ attitudes toward students with type 1 diabetes: A cross-sectional study

by María Yehisiri Martín–Báez, Candelaria de la Merced Díaz-González Introduction Type 1 diabetes mellitus (T1DM) is the most common chronic endocrine disorder in childhood, making teachers key agents in ensuring a safe school environment. The main objective of this study was to evaluate the attitudes and prejudices of teachers at Public Early Childhood and Primary Education Centres (ECPECs) in the municipality of San Bartolomé de Tirajana (SBTGC), on the island of Gran Canaria (Canary Islands, Spain), regarding the care of students with T1DM. Materials and methods A descriptive cross-sectional study was conducted. The target population consisted of 264 teachers from seven ECPECs schools in the municipality of SBTGC, Gran Canaria. Data collection was carried out using the validated instrument Teacher Negative Attitudes Index toward the Care of Students with Type 1 Diabetes Mellitus (INAPAD-18), which allowed for the evaluation of teachers’ attitudes and provided an answer to the study’s main objective. The research was approved by the Research and Drug Ethics Committee (CEIm) of Las Palmas. Results The final sample consisted of 126 participants, representing a participation rate of 47.72%, which did not reach the size required for statistical representativeness. A total of 15.87% of teachers reported currently having students diagnosed with T1DM. The mean number of years of experience working with students with this condition was 3.77 years [0–35years]. A marked gender disparity was observed, with a predominance of women (84.12%). The mean score obtained on the INAPAD-18 questionnaire was 47.02 (range: 18–90). In this instrument, lower scores indicate more favourable attitudes toward the care of students with T1DM. Although male participants showed more favourable attitudes compared to their women, this difference was not statistically significant (p > 0.05). Discussion/Conclusion The results indicate generally favourable attitudes, with moderately low INAPAD-18 scores. However, slight deficiencies were observed in teachers’ training and perception, consistent with findings from previous similar studies. The ECPEC schools Juan Grande and Las Dunas stood out for demonstrating the most positive attitudes. It is necessary for educational institutions to implement specific measures aimed at teacher training in order to improve attitudes and ensure appropriate attention to the needs of students with T1DM.

PLOS ONE

Tool-stone selection in the African Middle stone age at Sibhudu cave

by Patrick Schmidt, Klaus G. Nickel The raw materials people used for making stone tools may contain information about their territory, exchange routs or the selection criteria they employed during provisioning. In this study, we measure the mechanical properties of different tool-stones used by foragers living during the Middle Stone Age at Sibhudu Cave in South Africa. The site yielded a long and continuous sequence that saw transitions between different raw materials and tool forms. We evaluate the quality of these different stones for tool making and use, attempting to find correlations between selected raw materials and the tools made from them. We find that the raw materials used at Sibhudu have substantially different qualities, some being easy to flake but weak upon use, some being tough during stone knapping and resistant during use. Comparing these data with the appearance and disappearance of tool types throughout the Sibhudu sequence, we note that tool-stones requiring lower flaking forces were more often retouched than those requiring great forces. Elongated products, blades, were mostly made from materials with better fracture predictability, suggesting an understanding of the basic requirements for standardising the tool knapping process. Use-related qualities, such as resistance to dulling, appear to have been of lesser importance at Sibhudu. Our results suggest that the site’s occupants had a good understanding of the qualities of rocks for specific knapping processes.

PLOS ONE

Cross-context qualitative synthesis of a mobile obstetric referral emergency system (MORES) in Ghana and Liberia

by Camilla Bjelland, Joseph Sieka, Veronica Millicent Dzomeku, HaEun Lee, Wahdae-Mai Harmon-Gray, Emmanuel K. Nakua, Jody R. Lori Background To address the delayed provision of obstetric emergency care in Ghana and Liberia, our team previously implemented a mobile obstetric emergency referral system (MORES) connecting rural health facilities (RHFs) and district hospitals through a South-South-North triangular collaboration. This secondary qualitative data analysis aimed to synthesize the perceived barriers and benefits associated with the adoption of MORES in Ghana and Liberia. To guide this cross-context synthesis, we utilized Rogers’ Diffusion of Innovation Theory. Methods The analysis included individual interviews conducted among 29 district hospital providers and 33 rural health facility (RHF) workers in Liberia. In Ghana, 11 midwives at a district hospital participated in a focus group discussion. The codes were developed utilizing an inductive process. Thematic analysis was utilized to compare adoption across countries through the Diffusion of Innovation Theory. Findings Four themes were identified from the healthcare workers in Ghana and Liberia: compatibility, relative advantage, resource barriers, and limited implementation. According to healthcare workers, MORES was compatible with everyday workflow and had significant relative advantage, contributing positively to adoption. Healthcare workers were able to prioritize patient conditions upon presentation with increased referral information. Resource barriers and the limited implementation across districts restricted widespread adoption of MORES. Healthcare workers in both countries cited inconsistent access to ambulances as a barrier to complete obstetric referrals and in Liberia, the need for financial support for data and network connectivity was referenced. There were nuances by country, within the four themes. In Ghana, providers used MORES to facilitate follow-up on patients who did not complete referrals, contributing to MORES’ relative advantage. Conclusions MORES has the potential to reduce obstetric emergency referral delays in Ghana and Liberia. If the resource barriers and limited implementation of MORES are addressed, healthcare workers may continue to adopt and use the MORES system. Policy makers can address referral delays through the scale up of MORES, a compatible intervention with great relative advantage.

PLOS ONE

Markov reads Puškin, again: A statistical journey into the poetic world of Evgenij Onegin

by Angelo Maria Sabatini This study applies symbolic time series analysis and Markov modeling to explore the phonological structure of Evgenij Onegin—as captured through a graphemic vowel/consonant (V/C) encoding—and one contemporary Italian translation. Using a binary encoding inspired by Markov’s original scheme, we construct minimalist probabilistic models that capture both local V/C dependencies and large–scale sequential patterns. A compact four-state Markov chain is shown to be descriptively accurate and generative, reproducing key features of the original sequences such as autocorrelation and memory depth. All findings are exploratory in nature and aim to highlight structural regularities while suggesting hypotheses about underlying narrative dynamics. The analysis reveals a marked asymmetry between the Russian and Italian texts: the original exhibits a gradual decline in memory depth, whereas the translation maintains a more uniform profile. To further investigate this divergence, we introduce phonological probes — short symbolic patterns that link surface structure to narrative-relevant cues. Tracked across the unfolding text, these probes reveal subtle connections between graphemic form and thematic development, particularly in the Russian original. By revisiting Markov’s original proposal of applying symbolic analysis to a literary text and pairing it with contemporary tools from computational statistics and data science, this study shows that even minimalist Markov models can support exploratory analysis of complex poetic material. When complemented by a coarse layer of linguistic annotation, such models provide a general framework for comparative poetics and demonstrate that stylized structural patterns remain accessible through simple representations grounded in linguistic form.

PLOS ONE

Perceptions, attitudes, behaviours and barriers towards obesity among people with obesity and health care professionals in Indonesia: An exploratory online survey

by Sidartawan Soegondo, Gaga Irawan Nugraha, Farid Kurniawan, Ana Asmara Jannati, Dicky L. Tahapary Background The Awareness, Care, and Treatment In Obesity maNagement Asia Pacific (ACTION APAC) online survey identified perceptions, attitudes, and barriers to effective obesity care among People with Obesity (PwO) and Health Care Professionals (HCP) across nine APAC countries. Here, we present findings from Indonesia. Methods This was a cross-sectional, observational, descriptive survey in PwO (≥18-year-old) with self-reported body mass index of ≥25 kg/m2 and HCPs who spent ≥50% of their time in direct patient care. The survey was conducted between 20 April, 2022 to 11 May, 2022. The questionnaires were approved by the institutional review board as per local regulations. Findings A total of 1,000 PwO and 200 HCPs completed the survey. Notable differences were observed among PwO and HCPs in acknowledging obesity as a chronic disease (54% PwO and 90% HCPs), considering weight loss as PwO responsibility (91% PwO and 17% HCPs) and in agreeing that PwO were motivated to lose weight (76% PwO and 50% HCPs). Almost, two-thirds (67%) of PwO perceived themselves as either overweight or normal weight while only 30% discussed weight with their HCPs in the past five years. Financial concerns (45%) and assuming self-responsibility for weight loss (43%) were cited as the top reasons for not discussing. Only 53% HCPs initiated weight conversations, as they believed that PwO were either not motivated (55%) or not able to lose weight (51%). When discussed, most (68%) HCPs recommended lifestyle changes. Interpretation Our study identified gaps in understanding obesity as a disease and its management among PwO and HCPs, highlighting a need for increased awareness to improve obesity care in Indonesia.

PLOS ONE

The association of presbyphagia with urinary incontinence and Incontinence-related quality of life in nursing home residents: A cross-sectional study

by Ziya Yıldız Purpose The association between presbyphagia (age-related swallowing decline) and urinary incontinence (UI) remains poorly understood. This study therefore investigated the relationship between presbyphagia and both UI and incontinence-specific quality of life (I-QOL) in a distinct population of functionally independent healthy elderly in a nursing home. Method The presence of presbyphagia was determined in 73 participants in the nursing home using the 100 ml water swallowing test (100mlSwal) and the Eating Assessment Tool-10 (EAT-10) tests. UI was determined using the International Consultation on Incontinence Questionnaire Short (ICIQ-SF) and I-QOL was determined using the King’s Health Questionnaire (KHQ). The presence of presbyphagia, age and female gender confounding factors were analysed by multiple regression analysis. Multiple linear and binary logistic regression analyses were performed with presbyphagia, age, gender, and handgrip strength. Binary logistic regression was used to calculate odds ratios for UI presence. Results Presbyphagia was significantly associated with UI (p = .001). Individuals with presbyphagia had 7.47-fold higher odds of UI. Presbyphagia was also significantly associated with multiple I-QOL sub-domains, including incontinence impact, role limitation, physical limitation, and emotions (all p < .001). Male gender was associated with higher UI presence (OR=5.16), but not with UI severity. Age showed no significant associations with UI or I-QOL. Conclusion Presbyphagia is independently associated with UI presence and poorer I-QOL in nursing home residents. Male gender was associated with higher UI prevalence but similar severity and I-QOL to females. These findings suggest an independent association between presbyphagia and UI, thereby contributing to the formulation of hypotheses aimed at understanding the complex interactions between oral frailty and the urinary system. Further research is needed to elucidate underlying mechanisms and explore the potential clinical implications of this association. Trial registration ClinicalTrials.gov NCT06827561

PLOS ONE

Immunomodulatory effects of a multi-component pharmacological intervention on diabetic peripheral neuropathy in type 2 diabetic rats: An exploratory study

by Lu Zhang, Si Wang, Jie Lei, Lingrui Zeng, Ailin Lu, Yongqing Wu, Yuan Shi, Jing Yang, Mengrui Yuan, Hongyi Liu Background Diabetic peripheral neuropathy (DPN) is a common complication of type 2 diabetes mellitus (T2DM) and is closely linked to immune and inflammatory dysregulation. Multi-component pharmacological interventions have been explored as complementary approaches for metabolic and immune modulation; however, their effects on DPN and related mechanisms remain incompletely understood. Methods A rat model of T2DM-associated peripheral neuropathy was established, and a multi-component pharmacological intervention (MPCI) was administered for 8 weeks. Peripheral nerve dysfunction was evaluated by motor and sensory nerve conduction velocities (MNCV and SNCV), behavioral outcomes, and histological/ultrastructural assessments. In parallel, spleen tissues were collected for transcriptomic profiling. RNA sequencing was performed to identify differentially expressed genes and immune-related pathways, and representative molecules involved in inflammatory regulation were further validated using western blotting and quantitative real-time PCR in sciatic nerve tissue. Results MPCI administration significantly ameliorated peripheral nerve dysfunction in T2DM rats, as evidenced by improved nerve conduction velocities and pathological features. Transcriptomic analysis of spleen tissue revealed that MPCI was associated with broad remodeling of diabetes-related immune and inflammatory gene programs. In parallel, sciatic nerve analyses showed attenuation of NF-κB/c-Jun–associated inflammatory signaling and modulation of inhibitory regulators at both the protein and mRNA levels. Conclusion These findings indicate that MPCI improves T2DM-associated DPN and is associated with splenic immune remodeling and attenuation of peripheral nerve inflammatory signaling, providing exploratory evidence for associations between splenic immune transcriptomic remodeling and peripheral nerve inflammatory signaling.

PLOS ONE

Trends in the burden of sickle cell disorders in Sierra Leone, 1990–2023: An analysis of Global Burden of Disease Study 2023 estimates

by Monalisa M. J. Faulkner, Fatima Jalloh, Foray Mohamed Foray, Sahr L. Gborie, Mohamed B. Jalloh Background Sickle cell disease is a major cause of childhood mortality in sub-Saharan Africa, yet country-specific burden estimates for high-prevalence settings in West Africa remain limited. Objective To describe Global Burden of Disease (GBD) 2023 modeled estimates of sickle cell disorders burden in Sierra Leone from 1990 through 2023, including temporal trends, age and sex patterns, and demographic contributors to mortality change. Methods We analyzed GBD 2023 modeled estimates for sickle cell disorders in Sierra Leone, including prevalence, deaths, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) as absolute counts and age-standardized rates. Temporal trends in age-standardized rates were assessed using log-linear regression. The Kitagawa-Das Gupta decomposition partitioned the change in estimated deaths into population growth, age-structure change, and age-specific mortality-rate changes. Results Estimated prevalent cases increased from 48,689 (95% UI, 42,588−56,140) in 1990–90,498 (78,126−105,815) in 2023. Estimated deaths increased from 408 (288−579) to 635 (438−862), while the estimated age-standardized mortality rate declined from 10.2 to 7.9 per 100,000 (APC, −0.46%; 95% CI, −0.64 to −0.29). Decomposition attributed 159.6% of the net increase in deaths to population growth, −7.8% to age-structure change, and −51.8% to lower modeled age-specific rates. In 2023, an estimated 49.5% of deaths occurred before age 20. Point estimates suggested possible higher male mortality, but uncertainty intervals were wide and compatible with no clear sex difference. Conclusions GBD estimates suggest that Sierra Leone’s absolute burden of sickle cell disorders increased substantially between 1990 and 2023, while modeled rates declined. These modeled estimates highlight a growing absolute burden and persistent early-life mortality, supporting the need for improved surveillance, newborn screening, infection prophylaxis, hydroxyurea access, and longitudinal care systems.

PLOS ONE

Correction: Mammographic Assessment of a Geographically Defined Population at a Mastology Referral Hospital in São Paulo Brazil

by Simone Caetano, Juvenal Mottola Junior, Flora Finguerman, Suzan M. Goldman, Jacob Szejnfeld

PLOS ONE

<i>In silico</i> characterization of bioactive phytochemicals as antivirals targeting the reovirus σ1 protein for inhibiting σ1-mediated host cell entry

by Eitu Dey, Shipon Dey, Leu Nandi, Sayed Huzaifa Mumit, Refatul Arfat, Saifur Rahman Saif, Md. Monirul Islam Mammalian orthoreoviruses (MRVs), commonly known as reoviruses, are an emerging zoonotic threat that are known for their broad host tropism and potential for causing severe clinical pathology in both humans and animals. Despite this epidemic risk, currently, there are no approved therapeutic agents that are able to disrupt MRV transmission. The viral attachment protein sigma1 (σ1), mediating the entry of the virus into the host cells is a critical target for antiviral intervention. This study used an in silico structure-based drug design strategy to screen for bioactive phytochemicals that are capable of inhibiting the function of σ1. We screened a library of 376 bioactive phytochemicals with known antiviral potential against the σ1 receptor binding domain using molecular docking. Among the candidates, catechin gallate was the most potent inhibitor, possessing a superior binding affinity of −8.1 kcal/mol followed by bilobetin, which also showed a favorable binding affinity of −7.8 kcal/mol. Structural interaction analysis showed that catechin gallate and bilobetin occupies the active JAM-A binding pocket, forming stable interactions with some of the residues, including Gly381, Glu384, and Arg316, which are essential for the reovirus in the cellular attachment process. Subsequent pharmacokinetic and toxicity profiling proved that catechin gallate possessed favorable safety and drug-like characteristics, whereas bilobetin exhibited an unfavorable toxicity profile. In addition, molecular dynamics (MD) simulations supported the stability of σ1-catechin gallate complex relative to the σ1-bilobetin complex. Extensive post-trajectory analyses including RMSD, RMSF, Rg, SASA, and H-bond, showed that the binding of the catechin gallate significantly increases the rigidity and compactness of the protein. PCA indicated that the first three principal components (PC1-PC3) accounted for 74.1% and 76.2% of the total variance for catechin gallate and bilobetin, respectively, with the σ1-catechin gallate complex displaying a more compact conformational cluster consistent with greater stability. MM-GBSA analysis also showed favorable binding for both complexes, with estimated binding energies of −15.6097 ± 3.21 kcal/mol and −13.7327 ± 5.44 kcal/mol for the σ1-catechin gallate and σ1-bilobetin complexes, respectively, with catechin gallate showing comparatively stronger binding. Our results reveal a precise mechanism by which the lead compound catechin gallate sterically occludes the σ1 receptor-binding pocket, thereby likely abrogating viral attachment to the host cell. This comprehensive preclinical evaluation provides supporting evidence for the further development of catechin gallate using in vivo models and clinical trials as a promising antiviral candidate against reovirus infection.

PLOS ONE

The impact of India-ASEAN free trade agreement on trade flows: An application of augmented gravity model

by Prajakta Arote, Hastimal Sagara, Jadhav Chakradhar, Guruprasad Desai, Jadhav Pravin, Din Bandhu This study investigates the impact of the India-ASEAN Free Trade Agreement (FTA) on bilateral trade flows through an augmented gravity model. Employing panel data from 1990 to 2022 with 330 observations, the analysis incorporates key determinants such as GDP and population of India and ASEAN countries, tariff rates, geographic distance, historical ties, and levels of democracy, trade openness, and globalization. To address heteroskedasticity and cross-sectional dependency, we utilize Generalized Least Squares (GLS) estimations. Our analysis examines both export and import volumes between India and ASEAN nations. Results from Ordinary Least Squares (OLS) and GLS estimations indicate that ASEAN countries’ GDP positively influences trade volumes, while India’s GDP demonstrates mixed effects. Larger populations in both India and ASEAN countries significantly contribute to trade. Tariff rates and geographic distance are found to have a negative effect on both exports and imports. Interestingly, shared colonial history and language positively impact trade, whereas a common border yields mixed effects across the models. Control variables reveal that trade openness, democracy levels, and globalization have a positive and significant effect on India-ASEAN trade flows. The FTA dummy is positive and highly significant, confirming that AIFTA has substantially increased India’s bilateral trade with ASEAN. Based on these findings, we suggest that enhancing economic growth, mitigating geographic barriers, leveraging historical ties, and promoting trade openness and regional integration are essential strategies to bolster trade between India and ASEAN countries.

PLOS ONE

The supportive care needs of Iranian couples during postpartum hospitalization: A protocol of design, implementation and evaluation of intervention

by Zahra Rastad, Shirin Shahbazi Sighaldeh, Zahra Behboodi Moghadam, Shahla Faal Siahkal, Elham Ebrahimi Background The immediate postpartum period is marked by significant physiological and hormonal changes, which may present mothers with various social, emotional, and functional challenges. The goal of optimal postpartum hospice care is to sustain and enhance the health of both mothers and newborns while fostering a supportive environment for families and communities to address diverse health and social needs. Implementing comprehensive supportive care programs that offer full coverage of services for women can ensure that their needs are adequately met during this critical postpartum phase. Consequently, this study aims to investigate the supportive care requirements of couples during the postpartum period using a mixed-methods approach, along with the design and implementation of a needs-based intervention to improve health services during this essential time. Methods This study employs a multistage mixed-methods approach, structured in a sequential exploratory design consisting of three distinct phases. Initially, an exploratory qualitative study will be conducted utilizing a conventional content analysis framework to investigate the supportive care needs of couples during the postpartum hospitalization period. The second phase will involve a nominal group meeting in which the concerns and supportive care requirements identified by couples will be discussed in the presence of reproductive health specialists, policymakers, and experts. This collaborative effort will facilitate the prioritization of these needs. Following this prioritization, a comprehensive review of interventions and programs addressing couples’ supportive care needs during the postpartum hospitalization period on a global scale will be undertaken. Finally, after another panel of experts, the best intervention in this regard will be designed and consisted of a quantitative clinical trial aimed at evaluating the effectiveness of the intervention on the supportive care needs of Iranian couples during the postpartum period. Discussion The results of this study can lead to the design of a comprehensive supportive care program with comprehensive coverage of couples’ needs during the postpartum hospitalization period. The study aims to ensure that couples’ needs are met in this critical period. If this program is effective, it can be included in postpartum health care guidelines. Clinical trial registration No. IRCT20110621006854N8 (2024-11-16)

PLOS ONE

DG-LSTM-SA model: A deep gated LSTM network with self-attention mechanism for power generation and load forecasting

by Guoqiang Sun, Yang Zhao, Jianglong Li, Junfu Cui, Xiaoyan Qi Accurate forecasting of power generation and load demand is essential for the reliable operation of modern energy systems. Traditional recurrent neural networks (RNNs) often struggle to capture long-term dependencies in complex power time series, whereas recent Transformer-based models can introduce substantial computational overhead. To address these limitations, we propose a Deep Gated Long Short-Term Memory network with Self-Attention (DG-LSTM-SA). The proposed model combines a multi-layer gated architecture with hierarchically embedded self-attention modules, enabling it to adaptively emphasize informative time steps and capture complex temporal patterns without a prohibitive increase in parameters. We evaluated DG-LSTM-SA on three real-world energy datasets (NEPOOL, Yichang, and Solar-Energy). The results demonstrate that DG-LSTM-SA consistently outperforms ten baseline models. Compared with standard RNN variants such as LSTM and GRU, DG-LSTM-SA substantially reduces forecasting errors, decreasing Mean Absolute Error by more than 75%. Furthermore, relative to state-of-the-art attention-based models (e.g., Informer and Crossformer), DG-LSTM-SA achieves competitive accuracy while maintaining a distinct advantage in computational efficiency and training speed. Comprehensive ablation studies further confirm that the proposed design is robust, accurate, and practical for real-world grid dispatch and operational decision-making.

PLOS ONE

<i>Staphylococcus aureus agr</i>-type vs genetic background: molecular signatures determining differential metabolism and virulence potential

by Mariane Pivard, Julian Bär, Tomas Demeter, Srikanth Mairpady Shambat, Annelies S. Zinkernagel In Staphylococcus aureus, the quorum‑sensing accessory gene regulator (agr) system is the major virulence regulator. The four agr‑types (I-IV) have been associated with distinct infection outcomes, but their direct contribution to virulence regulation and metabolism has remained unresolved due to tight linkage between agr‑type and genetic background. To disentangle agr‑type‑specific effects, we used congenic Newman strains in which the native agr-locus has been replaced with each of the four agr-types, alongside a Δagr mutant. We performed RNA‑sequencing during early exponential (1h30), late exponential (6h), and stationary (12h) growth phases. Despite similar growth kinetics, agr‑types displayed distinct activation profiles based on agrA and RNAIII expressions. Agr-I and agr-IV showed early, strong expressions, agr-II displayed intermediate expressions and agr-III initiated weak expressions only in stationary phase. This agr‑type‑dependent activation timing was the dominant driver of global transcriptional changes. Early activation in agr‑I and agr‑IV induced robust expression of phenol‑soluble modulins, capsule biosynthesis genes, and pore‑forming toxins, whereas agr‑II and agr‑III expressed delayed or alternative virulence pathways, including upregulation of superantigen‑like genes. Among all types, agr‑IV exhibited the broadest transcriptional response, encompassing both virulence and metabolic pathways, including differential regulation of nucleotide and fructose metabolisms. Pairwise differential expression, over‑representation analysis, and gene‑set enrichment consistently revealed agr‑type‑specific virulence and metabolic programs. Agr‑III, which activated latest and weakest, showed limited transcriptional change until stationary phase, whereas agr‑I, agr‑II, and agr‑IV displayed progressively broader virulence and metabolic remodeling. Together, these findings demonstrate that agr‑type determines virulence and metabolic gene expression profiles primarily by dictating the timing and magnitude of agr-activation, even within an identical genetic background and growth environment. This work provides a systematic framework for understanding agr‑type‑specific regulatory strategies and their potential roles in S. aureus pathogenesis.

PLOS ONE

Identification and prediction of patients eligible for augmented rehabilitation in emergency gastrointestinal surgery (RAUCisable): A protocol for a single-centre, retrospective, observational study

by Émilien Arnaud, Gilles Dequen, Émilie Chivé, Delphine Lignier, William Gacquer, Momar Diouf, Thibaut Balcaen, Daniel Aiham Ghazali, Jean-Marc Regimbeau Introduction Conditions requiring emergency gastrointestinal surgery pose substantial challenges to healthcare systems and patient outcomes. For emergency gastrointestinal surgery, the mortality rate is higher than after other types of surgery, and 30-day readmission rates can exceed 30%. Unlike elective surgery (for which the application of enhanced recovery after surgery (ERAS) procedures has led to demonstrably better recovery), emergency surgery patients are still managed in an ad hoc manner. The Réhabilitation Augmentée pour les Urgences Chirurgicales (RAUC) multi-faceted research program has been designed to transform the care of patients undergoing emergency gastrointestinal surgery [7]. The ancillary RAUCisable study will develop a classification model that can automatically flag up RAUC-eligible patients early in their visit to the emergency department (ED). The study’s secondary objectives include the identification of key features and the prediction of time to surgery. Method RAUCisable is single-centre, retrospective, observational cohort study of electronic health records in the ED and digestive surgery department at Amiens-Picardie University Hospital (Amiens, France). All adult patients having attended the ED between January 1st, 2021, and December 31st, 2024, will be considered for inclusion. The primary classification outcome is eligibility for the RAUC pathway. Expected results We expect to identify ~2,400 RAUC-eligible patients from among ~250,000–300,000 ED visits over a 4-year period. These patients are likely to be significantly older than non-surgical ED patients (e.g., more over-65s), with a higher proportion of acute abdominal conditions (e.g., ~ 24% with appendicitis, ~ 13% with bowel obstruction, ~ 10% with peritonitis, etc.), and greater disease acuity on triage. Discussion The RAUCisable study’s findings will directly guide a concomitant, prospective, controlled study (RAUC-AMIENS) of the augmented recovery pathway, including ERAS elements and remote monitoring. Conclusion The RAUCisable study is a pivotal step toward digitally enhanced emergency surgical care. By learning from past data, we are seeking to improve the future management of emergency surgery patients through timely identification and targeted care pathways. This protocol article details our methodological approach for ensuring rigor and reproducibility. Trial registration NCT07037719

PLOS ONE

Analysis of rational use and misuse of antibiotics in emergency departments: A cross-sectional study

by Huseyin Gurbuz, Selda Aslan, Muhammet Emin Doğan, Mehmet Ali Çevik Objective To assess antibiotic prescribing frequency and the appropriateness of prescriptions based on established rational antibiotic use principles among adult patients evaluated in the emergency department. Methods This retrospective, cross-sectional study was conducted in the emergency department of a tertiary university hospital between 1 January and 30 June 2022. Adult patients (≥18 years) who received or were prescribed antibiotics were included. Demographic, clinical, and microbiological data were retrieved from the hospital information management system. Prescriptions were evaluated against rational antibiotic use criteria defined by the World Health Organization (WHO) and the Turkish Medicines and Medical Devices Agency (TİTCK). Results A total of 595 patients were analyzed (62.4% female; mean age, 31.1 ± 14.2 years). Antibiotics were prescribed in 95.8% of encounters. Amoxicillin–clavulanic acid was the most commonly used agent (58.7%), followed by amoxicillin (8.7%) and metronidazole (5.6%). Microbiological culture sampling was conducted in only 0.8% of cases. Among patients who received antibiotic therapy (n = 570), 87.2% of prescriptions were classified as appropriate and 12.8% were classified as inappropriate according to guideline-based evaluation. In the overall cohort, 4.2% of patients did not receive antibiotic therapy. Most treated patients received a single antibiotic (95.8%), whereas dual antibiotic therapy was infrequently used (4.0%). Conclusion Antibiotic prescribing in the emergency department was notably high, accompanied by critically low rates of microbiological investigation. The findings demonstrate a persistent reliance on empirical therapy. Enhancing diagnostic support, promoting culture-guided treatment, and incorporating routine antimicrobial de-escalation strategies may help strengthen rational antibiotic use and warrant further evaluation.

PLOS ONE

Predicting habitat suitability of Korean <i>Lindera</i> as Tertiary relict plants under climate change scenarios

by Jaewon Seol, Hye-jin Kwon, Songhie Jung, Yong-Chan Cho Climate change profoundly affects plant habitats and ecological niches, particularly among Tertiary relict flora—remnants of warm and humid climatic conditions that prevailed during the Tertiary period—which are recognized as highly climate-sensitive lineages. The genus Lindera (Lauraceae), a representative group of deciduous broad-leaved trees in East Asian temperate forests, provides an ideal model for examining shifts in habitat suitability and changes in predicted suitable environments under future climate change scenarios. In this study, we developed ensemble species distribution models (SDMs) using six algorithms to predict the distributions of four Lindera species—L. obtusiloba, L. glauca, L. erythrocarpa, and L. sericea—under three Shared Socioeconomic Pathway (SSP) scenarios (SSP1–2.6, SSP3–7.0, SSP5–8.5). Among the three categories of environmental variables, climatic factors exerted the greatest influence on habitat suitability, with temperature seasonality (bio4) and growing-season precipitation (gsp) identified as the primary determinants. With intensifying climate change, suitable habitats shifted northward and upward, accompanied by pronounced habitat losses across southern and central Korea. Despite its broad geographic range, L. obtusiloba exhibited an 81% reduction in suitable habitat, whereas L. sericea, due to its localized distribution, showed a 91% decrease and was identified as the most climate-vulnerable species. Ecological niche overlap (Schoener’s D) declined across all scenarios, indicating increasing ecological differentiation among species. Although the four Lindera species exhibited distinct spatial responses, all consistently experienced range contractions and reduced overlap in predicted suitable environments, indicating high vulnerability to climate change. These results suggest that intrinsic ecological traits, climatic sensitivity, and niche stability—rather than current geographic range extent—are key determinants of species persistence. Accordingly, Lindera species in southern Korea should be considered climate-vulnerable taxa, and conservation strategies should integrate the protection of climatically stable refugia with complementary conservation measures beyond natural habitats to ensure long-term persistence under future climate change.

PLOS ONE

Characterizing the <i>in vitro</i> and <i>in vivo</i> effect of bicarbonate on azithromycin activity against <i>Acinetobacter baumannii</i>

by Hadley Jaramillo, Matthew Slarve, Derek Long, Michelle Zorawik, Kristine Goy, Lauren Popel, Rosemary She, Brad Spellberg, Brian Luna Carbapenem-resistant Acinetobacter baumannii (CRAB), a Gram-negative bacterial pathogen, has been identified by Centers for Disease Control (CDC) as the top priority pathogen for which new antibiotics are needed. We found that the addition of bicarbonate at physiologically normal levels found in the blood (23.8 mM) increased susceptibility of A. baumannii clinical isolates (n = 63) to azithromycin and resulted in MIC50 shift from 64 mg/L in CAMHB to 1–2 mg/L in CAMHB + bicarbonate (23.8 mM) or RPMI-1640 respectively. To characterize in vivo efficacy in murine blood and lung infection models, mice were infected with A. baumannii and then mice were treated with a human equivalent dosing strategy of azithromycin. In vivo outcomes greatly depended on the infection model used. The bloodstream infection model showed a statistically significant increase in survival of the treatment group compared to the control group. However, that was not found with the oral aspiration infection model. We hypothesize that these in vivo results are due to the local differences of bicarbonate concentrations at the site of infection throughout the course of infection.

PLOS ONE

Effect of plastic composition in the combustion material on the Persistent Organic Pollutant content in smoked chicken meat

by Giang Do Hoang, Uyen Nguyen Thu, Luyen Nguyen Thi, Duong Hoang Thuy, Le Bui Thi Nhat, Nam Vu Duc, Xuyen Nguyen Thi, Thuy Le Minh, Tuan Anh Hoang Le, Tung Nguyen Ngoc, Dat Nguyen Tien Traditional food smoking in Vietnam often uses biomass fuels, but the incidental inclusion of plastics can generate toxic pollutants. This study evaluated the effects of polyethylene (PE), polystyrene (PS), and polyvinyl chloride (PVC) compared with clean wood on persistent organic pollutants (POPs) in smoked chicken, including PCBs, PCDD/Fs, and PAHs. Samples were smoked under controlled conditions, analyzed by GC–MS/MS, and assessed with univariate and multivariate statistics. Clean wood yielded low contamination, while PE introduced lighter PAHs and dioxins, PS was associated with mid-weight PAHs and specific PCBs (66, 195), and PVC caused the most severe contamination with 12 PCDD/Fs, 21 PCBs (e.g., 189, 101, 180, 153), and multiple carcinogenic PAHs (e.g., benzo[a]pyrene). Statistical tests confirmed significant differences among fuel groups (p < 0.01). The contamination gradient (W < PE < PS < PVC) highlights the urgent need to prohibit plastic-contaminated fuels in traditional smoking to safeguard food safety and public health.

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