bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiovascular function shows early impairment in asymptomatic adolescents diagnosed with type 1 diabetes mellitus: an ultrasound-derived myocardial work study
Authors: Ghirardo Martina , Cattapan Irene , Sabatino Jolanda , Pozza Alice , Fumanelli Jennifer , Avesani Martina , Gutierrez De Rubalcava Doblas Joaquin , Moretti Carlo , Castaldi Biagio , Di Salvo Giovanni 
Published: February 2025

BackgroundCardiac dysfunction and endothelial damage are known complications of type 1 diabetes mellitus (T1D) mainly affecting adults. However, some studies have shown that subclinical myocardial impairment already present during adolescence. Myocardial work (MW) has emerged as an afterload-independent tool that allows early identification of subclinical damage. This study aims to provide a comprehensive non-invasive cardiovascular evaluation of T1D adolescents using both conventional and advanced echocardiography.MethodsWe enrolled 31 patients, aged between 13 and 19 years, who were diagnosed with T1D for at least 10 years and were followed up by the Paediatric Diabetology Unit of our institution. We collected data relating to anthropometry, lifestyle, blood tests, glycemic control parameters, and conventional and advanced echocardiographic measurements. A comparison of MW parameters with the data from 31 age- and sex-matched healthy volunteers from a previous study in our lab was carried out.ResultsIn our population, the glycemic control parameters showed suboptimal control. While diastolic parameters were in the normal range for all the patients, E′ velocities and left atrial diameter were significantly worse in patients with poorer glycemic controls. Global longitudinal strain (GLS), global work index (GWI), and global work efficiency (GWE) were significantly lower in the T1D population compared to those in the healthy population (p &lt; 0.001), while global wasted work was significantly higher in the T1D population (p &lt; 0.001). Patients with stage 1 hypertension or a pre-hypertensive state exhibited pathological pulse wave velocities with values exceeding 8 m/s (&gt;99th percentile).ConclusionsTo the best of our knowledge, this was the first study to investigate MW in T1D adolescents. The descriptive parameters of GLS and MW showed subclinical cardiac damage already during this timeframe. Therefore, these tools should be integrated into the cardiovascular assessment of diabetic adolescents, and preventive strategies should be implemented to maximize glycemic and pressure control effectiveness.
Ruxolitinib synergizes with regulatory T cells to improve inflammation but has no added benefits in decreasing albuminuria in SLE
Authors: Lyu Mi-Ae , Tang Ximing , Raso Maria Gabriela , Huang Meixian , Zeng Ke , Sadeghi Tara , Flowers Christopher R. , Parmar Simrit 
Published: February 2025

BackgroundUmbilical cord blood (UCB)-derived CD4+CD25+CD127low regulatory T cells (Tregs) can decrease albuminuria and anti-dsDNA IgG in systemic lupus erythematosus (SLE). Ruxolitinib, a JAK/STAT inhibitor, has been shown to improve cutaneous manifestations of SLE. We hypothesize that the addition of ruxolitinib to UCB-Tregs may improve SLE outcomes.MethodsIn vitro cell suppression, phenotype change, IL-10 secretion, and cytokine levels in coculture supernatants were determined to quantify the impact of adding ruxolitinib to UCB-Tregs. A xenogeneic SLE model was utilized to study their in vivo combination.ResultsIn a dose-dependent manner, ruxolitinib addition synergizes with UCB-Tregs to suppress SLE-PBMC proliferation, inhibit CD8+ T cells, and reduce phosphorylation of STAT3/STAT5/AKT in CD8+ T cells. UCB-Treg and ruxolitinib combination also downregulates the soluble form of inflammatory cytokines including IFN-γ, IP-10, TNF-α, IL-6, sCD40L, IL-17A, IL-17F, IL-1α, and LIF in cocultures. The addition of ruxolitinib increases UCB-Treg cell persistence in peripheral blood in vivo and decreases the soluble form of human inflammatory cytokines including IFN-γ, TNF-α, and sCD40L in plasma along with improvement of skin lesions in SLE xenografts. Compared to control, significantly lesser CD3+, CD4+, CD8+, and Ki-67+ infiltrates are observed in the lung and kidney of UCB-Tregs and/or ruxolitinib recipients. No added benefit of addition of ruxolitinib is observed on the significant improvement in the urine albumin/creatinine ratio and the anti-dsDNA IgG levels induced by UCB-Tregs.ConclusionsOur results demonstrate that the addition of ruxolitinib to UCB-Tregs increases UCB-Tregs suppressor function and their persistence in vivo, downregulates systemic inflammation, and controls cutaneous SLE but does not add to UCB-Treg-mediated improvement in renal manifestations.
Comparative analysis of clinical characteristics and outcomes between carbapenem-resistant and carbapenem-sensitive Klebsiella pneumoniae infections: insights from a tertiary hospital in Northern China
Authors: Wang Bu , Zhang Wei , Zhang Hongxia , Li Maochen , Zhang Zhihua , Peng Xiaocui , Wang Na , Song Ning 
Published: February 2025

BackgroundTo compare the risk factors, clinical outcomes, and mortality rates between carbapenem-resistant Klebsiella pneumoniae (CRKP) and carbapenem-sensitive Klebsiella pneumoniae (CSKP) infections.MethodsA retrospective cohort study was conducted on patients with Klebsiella pneumoniae infections admitted to a tertiary hospital in Zhangjiakou, China. The research period is from January 2021 to December 2022. Data were analyzed using SPSS 24.0 and R. Univariate analysis identified potential risk factors for CRKP infections using appropriate statistical methods, followed by multivariable logistic regression to determine independent risk factors. Mortality rates between CRKP and CSKP groups were compared using chi-square tests, and survival curves were generated with the Kaplan–Meier method.ResultsThe study included 283 patients, with 104 (36.7%) infected by CRKP and 179 (63.3%) by CSKP. CRKP patients had significantly higher body temperature, white blood cell counts, and inflammatory markers, while showing lower diastolic blood pressure and oxygen saturation (p &lt; 0.05). CRKP infections were predominantly found in the ICU (49%) and mainly isolated from sputum (59%). Independent risk factors for CRKP included elevated C-reactive protein (OR = 1.02) and solid tumors (OR = 18.186). CRKP patients experienced longer hospital stays (25 days vs. 12 days for CSKP), longer ICU stays (13 days vs. 7 days), and higher 30-day mortality (23.1% vs. 17.9%, p = 0.012). The deceased group had elevated procalcitonin and creatinine levels, longer prothrombin time, and a greater need for mechanical ventilation compared to survivors (p &lt; 0.05).ConclusionPatients with CRKP infections had higher mortality rates and longer hospital stays than those with CSKP infections. Previous hospitalization, hospitalization in an ICU, and mechanical ventilation were independent risk factors for CRKP infection.
Clinical validation and optimization of machine learning models for early prediction of sepsis
Authors: Liu Xi , Li Meiyi , Liu Xu , Luo Yuting , Yang Dong , Ouyang Hui , He Jiaoling , Xia Jinyu , Xiao Fei 
Published: February 2025

IntroductionSepsis is a global health threat that has a high incidence and mortality rate. Early prediction of sepsis onset can drive effective interventions and improve patients’ outcome.MethodsData were collected retrospectively from a cohort of 2,329 adult patients with positive bacteria cultures from a tertiary hospital in China between October 1, 2019 and September 30, 2020. Thirty six clinical features were selected as inputs for the models. We trained models in predicting sepsis by machine learning (ML) methods, including logistic regression, decision tree, random forest (RF), multi-layer perceptron, and light gradient boosting. We evaluated the performance of the five ML models and the evaluation metrics were: area under the ROC curve (AUC), accuracy, F1-score, sensitivity and specificity. The data of another cohort of 2,286 patients between October 1, 2020 and April 1, 2022 were used to validate the performance of the model performing best in the in the internal validation set. Shapley additive explanations (SHAP) method was applied to evaluate feature importance and explain the predictions of this model.ResultsOf the five machine learning models developed, the RF model demonstrated the best performance in terms of AUC (0.818), F1 value (0.38), and sensitivity (0.746). The RF model also has a comparable AUC (0.771) in the external validation set. The SHAP method identified procalcitonin, albumin, prothrombin time, and sex as the important variables contributing to the prediction of sepsis.DiscussionThe RF model we developed showed the greatest potential for early prediction of sepsis in admitted patients, which could aid clinicians in their decision-making process. Our findings also suggested that male patients with bacterial infections and high procalcitonin levels, lower albumin levels, or prolonged prothrombin times were more likely to develop sepsis.
Machine learning prediction of obesity-associated gut microbiota: identifying Bifidobacterium pseudocatenulatum as a potential therapeutic target
Authors: Wu Hao , Li Yuan , Jiang Yuxuan , Li Xinran , Wang Shenglan , Zhao Changle , Yang Ximiao , Chang Baocheng , Yang Juhong , Qiao Jianjun 
Published: February 2025

BackgroundThe rising prevalence of obesity and related metabolic disorders highlights the urgent need for innovative research approaches. Utilizing machine learning (ML) algorithms to predict obesity-associated gut microbiota and validating their efficacy with specific bacterial strains could significantly enhance obesity management strategies.MethodsWe leveraged gut microbiome data from 1,563 healthy individuals and 2,043 overweight patients sourced from the GMrepo database. We assessed the anti-obesity effects of Bifidobacterium pseudocatenulatum through experimentation with Caenorhabditis elegans and C3H10T1/2 cells.ResultsOur analysis revealed a significant correlation between gut bacterial composition and body weight. The top 40 bacterial species were utilized to develop ML models, with XGBoost demonstrating the highest predictive accuracy. SHAP analysis indicated a negative association between the relative abundance of six bacterial species, including B. pseudocatenulatum, and body mass index (BMI). Furthermore, B. pseudocatenulatum was shown to reduce lipid accumulation in C. elegans and inhibit lipid differentiation in C3H10T1/2 cells.ConclusionBifidobacterium pseudocatenulatum holds potential as a therapeutic agent for managing diet-induced obesity, underscoring its relevance in microbiome-based obesity research and intervention.
Adherence to customized vestibular rehabilitation therapy: influencing factors and clinical implications in vestibulopathy
Authors: Im Yeon Hee , Lee Hyun Jin , Jeon Eun-Ju 
Published: February 2025

ObjectiveCustomized vestibular rehabilitation therapy (CVRT) is an effective treatment approach for various vestibular disorders. However, low adherence significantly limits its efficacy, and factors influencing adherence remain underexplored. This study aimed to identify factors affecting adherence to CVRT across major vestibulopathy categories, including acute unilateral vestibular hypofunction (AUVH), chronic unilateral vestibular hypofunction (CUVH), and bilateral vestibular hypofunction (BVH).MethodsA retrospective analysis of 90 patients who were prescribed four sessions of CVRT and underwent the therapy was conducted. Patients were classified as adherent (≥3 sessions) or non-adherent (≤2 sessions). Demographic characteristics, baseline questionnaire scores, and vestibular function test (VFT) results were compared. Change in questionnaire scores and VFT results before and after CVRT, as well as mid-treatment follow-up questionnaire scores were analyzed.ResultsAdherence rates were highest in CUVH (86.7%) and lowest in BVH (46.2%). Among patients with AUVH, poor functional reach test scores were significantly associated with lower adherence (p = 0.045). In the CUVH category, patients with mild dizziness in the initial questionnaire were non-adherent (p = 0.019). CVRT improved subjective dizziness symptoms and VFT parameters, with the greatest gains observed in AUVH. However, no significant differences in symptom improvement were found between adherent and non-adherent patients. Patients whose symptoms improved rapidly to a mild degree after starting the CVRT were more likely to be non-adherent, with this tendency being especially pronounced in those with AUVH.ConclusionAdherence to CVRT varies by vestibulopathy category and is influenced by baseline symptom severity. Tailoring CVRT strategies based on individual clinical profiles may enhance adherence and optimize therapeutic outcomes.
Application of a new highly multiplexed amplicon sequencing tool to evaluate Plasmodium falciparum antimalarial resistance and relatedness in individual and pooled samples from Dschang, Cameroon
Authors: Sadler Jacob M. , Simkin Alfred , Tchuenkam Valery P. K. , Gerdes Gyuricza Isabela , Fola Abebe A. , Wamae Kevin , Assefa Ashenafi , Niaré Karamoko , Thwai Kyaw , White Samuel J. , Moss William J. , Dinglasan Rhoel R. , Nsango Sandrine Eveline , Tume Christopher B. , Parr Jonathan B. , Ali Innocent Mbulli , Bailey Jeffrey A. , Juliano Jonathan J. 
Published: February 2025

BackgroundResistance to antimalarial drugs remains a major obstacle to malaria elimination. Multiplexed, targeted amplicon sequencing is being adopted for surveilling resistance and dissecting the genetics of complex malaria infections. Moreover, genotyping of parasites and detection of molecular markers drug resistance in resource-limited regions requires open-source protocols for processing samples, using accessible reagents, and rapid methods for processing numerous samples including pooled sequencing.MethodsPlasmodium falciparum Streamlined Multiplex Antimalarial Resistance and Relatedness Testing (Pf-SMARRT) is a PCR-based amplicon panel consisting of 15 amplicons targeting antimalarial resistance mutations and 9 amplicons targeting hypervariable regions. This assay uses oligonucleotide primers in two pools and a non-proprietary library and barcoding approach.ResultsWe evaluated Pf-SMARRT using control mocked dried blood spots (DBS) at varying levels of parasitemia and a mixture of 3D7 and Dd2 strains at known frequencies, showing the ability to genotype at low parasite density and recall within-sample allele frequencies. We then piloted Pf-SMARRT to genotype 100 parasite isolates collected from uncomplicated malaria cases at three health facilities in Dschang, Western Cameroon. Antimalarial resistance genotyping showed high levels of sulfadoxine-pyrimethamine resistance mutations, including 31% prevalence of the DHPS A613S mutation. No K13 candidate or validated artemisinin partial resistance mutations were detected, but one low-level non-synonymous change was observed. Pf-SMARRT’s hypervariable targets, used to assess complexity of infections and parasite diversity and relatedness, showed similar levels and patterns compared to molecular inversion probe (MIP) sequencing. While there was strong concordance of antimalarial resistance mutations between individual samples and pools, low-frequency variants in the pooled samples were often missed.ConclusionOverall, Pf-SMARRT is a robust tool for assessing parasite relatedness and antimalarial drug resistance markers from both individual and pooled samples. Control samples support that accurate genotyping as low as 1 parasite per microliter is routinely possible.
Identification and functional analysis of Wall-Associated Kinase genes in Nicotiana tabacum
Authors: Li Ling , Cao Linggai , Li Jintao , Zhang Zhiqiang , Liu Jie , Ren Zhongying , Zhang Jie , Wang Rengang , Miao Yangfan , Yu Shizhou , Li Wei 
Published: February 2025

IntroductionWall-associated kinases (WAKs) are pivotal in linking plant cell walls to intracellular signaling networks, thereby playing essential roles in plant growth, development, and stress responses. MethodsThe bioinformatics analysis was employed to identify WAK genes in tobacco. The expression levels of NtWAK genes were assessed by qRT-PCR. The subcellular localization of WAK proteins was observed in tobacco cells and Arabidopsis protoplasts. Kinase activity of the WAK proteins was evaluated through in vitro assays. ResultsWe conducted a comprehensive genome-wide identification and analysis of the WAK gene family in tobacco (Nicotiana tabacum). A total of 44 WAK genes were identified in the tobacco genome, which were further classified into three distinct groups. Phylogenetic analysis comparing tobacco WAKs (NtWAKs) with Arabidopsis WAKs (AtWAKs) revealed species-specific expansion of these genes. The WAK proteins within each group displayed similar gene structures and conserved motif distributions. Promoter region analysis indicated that cis-elements of NtWAK genes are primarily involved in regulating plant growth and development, phytohormone signaling, and stress responses. Expression profiling under NaCl, PEG, and ABA treatments suggested that certain NtWAK genes may play key roles in modulating responses to abiotic stress. Three-dimensional structural predictions and subcellular localization analysis showed that NtWAK proteins from the three subgroups exhibit high cytoplasmic similarity and are primarily located to the plasma membrane. Kinase activity assay confirmed that they possess phosphorylation activity. DiscussionThis study represents the first genome-wide analysis of the WAK gene family in N. tabacum, laying the groundwork for future functional investigations.
Relationship between TyG-related index and hearing loss in people over 45 s in China
Authors: Wang Chao , Shi Mengdi , Xie Liangzhen , Jiang Chenhao , Li Yunxin , Li Jingxiao , Li Shulin , Li Yan 
Published: February 2025

BackgroundTriglycerides and fasting glycemic index are biomarkers used to assess the risk of insulin resistance and metabolic syndrome. It and its derivatives such as the TyG-BMI index are currently able to reflect the degree of insulin resistance and are closely related to a variety of metabolic diseases. The relationship between the TyG-BMI index and hearing loss remains underexplored, particularly in the context of aging and public health. This study investigates the association of the TyG index, BMI index, and TyG-BMI index with hearing loss, with a focus on their potential implications for the aging population.MethodsData from the China Health and Retirement Longitudinal Study (CHARLS) database were analyzed using R software. We applied multi-factor logistic regression, linear regression, restricted cubic splines, and subgroup analyses to assess the impact of the TyG index, BMI index, and TyG-BMI index on hearing loss across different age groups.ResultsThe TyG index was not significantly associated with hearing loss. However, both the BMI index and the TyG-BMI index exhibited a positive correlation with hearing loss, particularly among older individuals. The results suggest that as the population ages, higher BMI and TyG-BMI indices may increase the risk of hearing impairment.ConclusionWhile the TyG index does not show a significant link to hearing loss, higher BMI and TyG-BMI indices are associated with an increased risk of hearing loss, especially in older adults. These findings highlight the importance of considering aging-related factors in public health initiatives aimed at preventing hearing loss. Further research is needed to elucidate the mechanisms underlying these associations and to develop age-inclusive strategies for addressing hearing impairment in the aging population.
Analysis of acute non-pharmaceutical toxic exposures in children: a 5-year retrospective study
Authors: Qu Yanning , Tang Rui , Duan Zhuyan , Sheng Mengyi , Wang Hui , Liu Shuang , Li Jiao , Guo Linlin , Guo Linying , Zheng Si 
Published: February 2025

ObjectiveThis study aims to systematically analyze the epidemiological characteristics, clinical interventions and outcomes of children with acute non-pharmaceutical toxic exposures.MethodsThis retrospective study included all children with acute non-pharmaceutical toxic exposure admitted to the emergency department of the Capital Institute of Pediatrics between January 1, 2019, and December 31, 2023. Eligible patients were triaged into red, yellow, and green groups according to their severity condition. Clinical information including demographics, exposure details, clinical manifestation, laboratory results, treatments, and outcomes were extracted from electronic medical records. Univariate and multivariate logistic regression analyses were conducted to identify risk factors associated with hospitalization.ResultsOverall, a total of 718 patients with acute non-pharmaceutical toxic exposures was included in this study, infants and toddlers accounting for 57.9%. The male-to-female ratio was 1.16:1. The majority exposure events occurred at home (89.3%) and in urban settings (78.4%). Accidental poisoning was the predominant cause, accounting for 94.7%, and the primary route of exposure was oral (93.6%). Mercury was the most common exposed substance, representing 18.8% of cases, particularly among preschool-aged children (31.7%). Patients triaged to red zone had a higher proportion of clinical manifestation and required more aggressive treatments. Although most patients discharged without treatment (78.4%), 19.1% need emergency observation, and 2.5% required hospitalization. Logistic regression analysis showed that corrosive household products exposure (OR = 42.747, 95% CI[5.041–362.520]), skin and mucosal damage (OR = 37.052, 95% CI[5.339–257.153]), pesticides exposure (OR = 33.322, 95% CI[3.863–287.423]), heavy metals exposure (OR = 31.636, 95% CI[1.471–680.210]), neurological manifestation (OR = 22.656, 95% CI[4.766–107.711]), positive toxicology results (OR = 15.105, 95% CI[6.584–34.656]), industrial products exposure (OR = 10.294, 95% CI[1.144–92.641]), and intentional poisoning (OR = 3.060, 95% CI[1.733–5.405]) associated with hospitalization.ConclusionPediatric patients exposed to some specific toxicants like industrial products and corrosive household products might associated with a higher risk of severe clinical outcomes. Advocating for enhanced safety regulations or educations and public health initiatives to mitigate the incidence of such exposures is still important for protecting children's health.