bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shotgun metagenomics reveals the interplay between microbiome diversity and environmental gradients in the first marine protected area in the northern Arabian Gulf
Authors: Fakhraldeen Saja A. , Madhusoodhanan Rakhesh , Habibi Nazima , Al-Haddad Sakinah , Alagarsamy Surendraraj , Habeebullah Sabeena F. K. , Al-Zakri Walid M. , Thuslim Fathima , Fernandes Loreta , Al-Yamani Faiza , Al-Said Turki 
Published: January 2025

IntroductionThe northwest Arabian Gulf encounters significant anthropogenic pressures, including nutrient enrichment from coastal development and effluent discharge.MethodsThis study presents the first shotgun metagenomics-based characterization of microbial communities in Kuwaiti waters of the northwest Arabian Gulf, focusing on Kuwait’s first Marine Protected Area (MPA) in Sulaibikhat Bay, a vital nursery ground for commercially important fish.ResultsAnalysis revealed significantly higher microbial diversity within the MPA compared to adjacent waters, with Rhodobacteraceae (27.8%) and Flavobacteriaceae (15.3%) being dominant. Elevated inorganic phosphorus, nitrogen, and salinity were key factors driving this diversity. Multivariate analysis highlighted phosphate as a critical component affecting the MPA microbial community structure, particularly for the families Microbacteriaceae, Flavobacteriaceae, and Rhodobacteraceae.DiscussionThis study underscores the ecological importance of MPAs and highlights the impact of nutrient enrichment and other environmental stressors on microbial diversity, emphasizing the need to reduce nutrient influx to mitigate eutrophication and enhance marine ecosystem resilience in stressed environments.
Prevalence and characterization of IncQ1α-mediated multi-drug resistance in Proteus mirabilis Isolated from pigs in Kunming, Yunnan, China
Authors: Liu Hongmei , Xia Na , Suksawat Fanan , Tengjaroenkul Bundit , Hu Yue , Zhou Xiaofeng , Li Xiaojiang , Huang Cuiqin , Bao Yinli , Wu Qiong , Zhang Chunrong , Angkititrakul Sunpetch , Xiang Bin , Wu Xin 
Published: January 2025

BackgroundProteus mirabilis is a conditionally pathogenic bacterium that is inherently resistant to polymyxin and tigecycline, largely due to antibiotic resistance genes (ARGs). These ARGs can be horizontally transferred to other bacteria, raising concerns about the Inc plasmid-mediated ARG transmission from Proteus mirabilis, which poses a serious public health threat. This study aims to investigate the presence of Inc plasmid types in pig-derived Proteus mirabilis in Kunming, Yunnan, China.MethodsFecal samples were collected from pig farms across six districts of Kunming (Luquan, Jinning, Yiliang, Anning, Songming, and Xundian) from 2022 to 2023. Proteus mirabilis isolates were identified using IDS and 16S rRNA gene sequencing. Then, positive strains underwent antimicrobial susceptibility testing and incompatibility plasmid typing. Multi-drug-resistant isolates with positive incompatibility plasmid genes were selected for whole-genome sequencing. Resistance and Inc group data were then isolated and compared with 126 complete genome sequences from public databases. Whole-genome multi-locus sequence typing, resistance group analysis, genomic island prediction, and plasmid structural gene analysis were performed.ResultsA total of 30 isolates were obtained from 230 samples, yielding a prevalence of 13.04%. All isolates exhibited multi-drug resistance, with 100% resistance to cotrimoxazole, erythromycin, penicillin G, chloramphenicol, ampicillin, and streptomycin. Among these, 15 isolates tested positive for the IncQ1α plasmid repC gene. The two most multi-drug-resistant and repC-positive strains, NO. 15 and 21, were sequenced to compare genomic features on Inc groups and ARGs with public data. Genome analysis revealed that the repC gene was primarily associated with IncQ1α, with structural genes from other F-type plasmids (TraV, TraU, TraN, TraL, TraK, TraI, TraH, TraG, TraF, TraE/GumN, and TraA) also present. Strain NO. 15 carried 33 ARGs, and strain NO. 21 carried 38 ARGs, conferring resistance to tetracyclines, fluoroquinolones, aminoglycosides, sulfonamides, peptides, chloramphenicol, cephalosporins, lincomycins, macrolides, and 2-aminopyrimidines.ConclusionThe repC gene is primarily associated with IncQ1α, with structural genes from other F-type plasmids. A comparison with 126 public genome datasets confirmed this association.
Single-channel attention classification algorithm based on robust Kalman filtering and norm-constrained ELM
Authors: He Jing , Huang Zijun , Li Yunde , Shi Jiangfeng , Chen Yehang , Jiang Chengliang , Feng Jin 
Published: January 2025

IntroductionAttention classification based on EEG signals is crucial for brain-computer interface (BCI) applications. However, noise interference and real-time signal fluctuations hinder accuracy, especially in portable single-channel devices. This study proposes a robust Kalman filtering method combined with a norm-constrained extreme learning machine (ELM) to address these challenges.MethodsThe proposed method integrates Discrete Wavelet Transformation (DWT) and Independent Component Analysis (ICA) for noise removal, followed by a robust Kalman filter enhanced with convex optimization to preserve critical EEG components. The norm-constrained ELM employs L1/L2 regularization to improve generalization and classification performance. Experimental data were collected using a Schulte Grid paradigm and TGAM sensors, along with publicly available datasets for validation.ResultsThe robust Kalman filter demonstrated superior denoising performance, achieving an average AUC of 0.8167 and a maximum AUC of 0.8678 on self-collected datasets, and an average AUC of 0.8344 with a maximum of 0.8950 on public datasets. The method outperformed traditional Kalman filtering, LMS adaptive filtering, and TGAM’s eSense algorithm in both noise reduction and attention classification accuracy.DiscussionThe study highlights the effectiveness of combining advanced signal processing and machine learning techniques to improve the robustness and generalization of EEG-based attention classification. Limitations include the small sample size and limited demographic diversity, suggesting future research should expand participant groups and explore broader applications, such as mental health monitoring and neurofeedback.
Preoperative prediction of pituitary neuroendocrine tumor invasion using multiparametric MRI radiomics
Authors: Yang Qiuyuan , Ke Tengfei , Wu Jialei , Wang Yubo , Li Jiageng , He Yimin , Yang Jianxian , Xu Nan , Yang Bin 
Published: January 2025

ObjectiveThe invasiveness of pituitary neuroendocrine tumor is an important basis for formulating individualized treatment plans and improving the prognosis of patients. Radiomics can predict invasiveness preoperatively. To investigate the value of multiparameter magnetic resonance imaging (mpMRI) radiomics in predicting pituitary neuroendocrine tumor invasion into the cavernous sinus (CS) before surgery.Patients and methodsThe clinical data of 133 patients with pituitary neuroendocrine tumor (62 invasive and 71 non-invasive) confirmed by surgery and pathology who underwent preoperative mpMRI examination were retrospectively analyzed. Data were divided into training set and testing set according to different field strength equipment. Radiomics features were extracted from the manually delineated regions of interest in T1WI, T2WI and CE-T1, and the best radiomics features were screened by LASSO algorithm. Single radiomics model (T1WI, T2WI, CE-T1) and combined radiomics model (T1WI+T2WI+CE-T1) were constructed respectively. In addition, clinical features were screened to establish clinical model. Finally, the prediction model was evaluated by ROC curve, calibration curve and decision curve analysis (DCA).ResultsA total of 10 radiomics features were selected from 306 primitive features. The combined radiomics model had the highest prediction efficiency. The area under curve (AUC) of the training set was 0.885 (95% CI, 0.819-0.952), and the accuracy, sensitivity, and specificity were 0.951,0.826, and 0.725. The AUC of the testing set was 0.864 (95% CI, 0.744-0.985), and the accuracy, sensitivity, and specificity were 0.829,0.952, and 0.700. DCA showed that the combined radiomics model had higher clinical net benefit.ConclusionThe combined radiomics model based on mpMRI can effectively and accurately predict the invasiveness of pituitary neuroendocrine tumor to CS preoperatively, and provide decision-making basis for clinical individualized treatment.
Mechanistic insights into HPV-positivity in non-smokers and HPV-negativity in smokers with head and neck cancer
Authors: Hoffmann Markus , Hille Susanne , Fazel Asita , Laudien Martin , Wiegand Susanne , Müller Martin , Müller Oliver J. , Quabius Elgar Susanne 
Published: January 2025

IntroductionSeveral aspects of the involvement of HPV in the pathogenesis of HPV-associated diseases remain poorly understood including mechanistic aspects of infection and the question of why the majority of HPV-positive HNSCC-patients are non-smokers, whereas HPV-negatives are smokers. Our previous research, based on 1,100 patient samples, hypothesized an explanation for this phenomenon: Smoking induces upregulation of a mucosal protective protein (SLPI), which competes with HPV for binding to Annexin A2 (AnxA2), pivotal for HPV cell entry. Here we investigate the mechanistic aspects of our hypothesis using transfection assays.MethodsHaCaT and HeLa cell lines were used to investigate the effects of shRNA transfection and nicotine exposure on HPV16-PsV-uptake. Cells were treated with Lipofectamine™ RNAiMAX for 48 or 72 hours with specific shRNA-concentrations, while nicotine was added to the cell medium at the indicated concentrations. Protein isolation, SLPI- and AnxA2-quantification, LDH cytotoxicity assessment, HPV16-PsV-uptake measurement, mRNA-isolation, cDNA-synthesis and RT-qPCR were performed.ResultsIn vitro transfection experiments with HPV16 pseudovirions (PsVs) showed that PsVs entered cells significantly better when SLPI was downregulated and significantly less when AnxA2 was downregulated. Nicotine exposure increased SLPI levels and reduced PsV uptake.ConclusionsThe overexpression of SLPI caused by tobacco-smoking can hinder HPV cell entry by binding to AnxA2 and thus prevent successful HPV infection. Conversely, non-smokers have lower SLPI-levels, associated with an excess of unbound AnxA2, favoring HPV cell-entry. These findings support our hypothesis, suggesting a paradigm shift in understanding virus-related pathogenesis, particularly in the head and neck region, and the nature of HPV infection.
A nomogram for predicting neonatal acute respiratory distress syndrome in patients with neonatal pneumonia after 34 weeks of gestation
Authors: Yu Aosong , Hou Huanhuan , Ran Lingyi , Sun Xiaojia , Xin Wanchun , Feng Tong 
Published: January 2025

ObjectiveTo establish a prediction nomogram for early prediction of neonatal acute respiratory distress syndrome (NARDS).MethodsThis is a retrospective cross-sectional study conducted between January 2021 and December 2023. Clinical characteristics and laboratory results of cases with neonatal pneumonia were compared in terms of presence of NARDS diagnosis based on the Montreux Definition. The NARDS group and non-NARDS group were then compared to establish a prediction nomogram for early prediction of NARDS. The predictive accuracy and compliance of the model were evaluated using subject operating characteristic curves, area under the ROC curve, and calibration curves, and the model performance was estimated by self-lifting weight sampling. The Hosmer–Lemeshow test was used to assess the goodness of fit of the model.FindingsNARDS group consisted of 104, non-NARDS group consisted of 238 newborns in our study. Gestational age, triple concave sign, blood glucose measurement after birth (Glu), Apgar score at the 5th minute (Apgar5), neutrophil count (ANC) and platelet count (PLT) are independent predictors of NARDS in late preterm and term newborns who present with progressive respiratory distress and require varying degrees of respiratory support within the first 24 h of life to minimize work of breathing and restore organismal oxygenation. The area under the ROC curve was 0.829 (95% CI = 0.785–0.873), indicating the model's strong predictive power. In addition, decision curve analysis showed that the model had significantly better net benefits.ConclusionIn this study, a predictive column-line plot was constructed based on six clinically accessible conventional variables. Early application of this model has a better predictive effect on the early diagnosis of NARDS, thus facilitating more timely and effective interventions.
Duvelisib is a novel NFAT inhibitor that mitigates adalimumab-induced immunogenicity
Authors: Bhingarkar Aboli , Wang Yuyin , Hoshitsuki Keito , Eichinger Katherine Marie , Rathod Sanjay , Zhu Yin , Lyu He , McNutt Andrew T. , Moreland Larry W. , McDermott Lee , Koes David R. , Fernandez Christian A. 
Published: January 2025

IntroductionTNFα inhibitor (TNFi) immunogenicity in rheumatoid arthritis (RA) is a major obstacle to its therapeutic effectiveness. Although methotrexate (MTX) can mitigate TNFi immunogenicity, its adverse effects necessitate alternative strategies. Targeting nuclear factor of activated T cells (NFAT) transcription factors may protect against biologic immunogenicity. Therefore, developing a potent NFAT inhibitor to suppress this immunogenicity may offer an alternative to MTX.MethodsWe performed a structure-based virtual screen of the NFATC2 crystal structure to identify potential small molecules that could interact with NFATC2. For validation, we investigated the effect of the identified compound on NFAT transcriptional activity, nuclear localization, and binding to the NFAT consensus sequence. In vivo studies assessed the ability of the compound to protect against TNFi immunogenicity, while ex vivo studies evaluated its effect on CD4+ T cell proliferation and B cell antibody secretion.ResultsWe identified duvelisib (DV) as a novel NFATC2 and NFATC1 inhibitor that attenuates NFAT transcriptional activity without inhibiting calcineurin or NFAT nuclear localization. Our results suggest that DV inhibits NFAT independently of PI3K by interfering with nuclear NFAT binding to the NFAT consensus promoter sequence. DV significantly protected mice from adalimumab immunogenicity and attenuated ex vivo CD4+ T cell proliferation and B cell antibody secretion.DiscussionDV is a promising NFAT inhibitor that can protect against TNFi immunogenicity without inhibiting calcineurin phosphatase activity. Our results suggest that the future development of DV analogs may be of interest as agents to attenuate unwanted immune responses.
Protective effects of Cordyceps militaris against hepatocyte apoptosis and liver fibrosis induced by high palmitic acid diet
Authors: Tsai Wan-Ting , Situmorang Jiro Hasegawa , Kuo Wei-Wen , Kuo Chia-Hua , Lin Shinn-Zong , Huang Chih-Yang , Ho Tsung-Jung 
Published: January 2025

BackgroundFatty Liver Disease (FLD) progresses from steatosis to steatohepatitis and, if left untreated, can lead to irreversible conditions such as cirrhosis and hepatocarcinoma. The etiology of FLD remains unclear, but factors such as overconsumption, poor diet, obesity, and diabetes contribute to its development. Palmitic acid (PA) plays a significant role in FLD progression by inducing apoptosis, inflammation, oxidative stress, and endoplasmic reticulum (ER) stress in hepatocytes. Cordyceps militaris (CM), a fungus with various biological activities, including antioxidant properties is examined both in vitro and in vivo to assess its effectiveness in mitigating PA-induced hepatocyte apoptosis and preventing FLD progression.PurposeThis study aims to investigate the potential and mechanism of CM in combating FLD, particularly in inhibiting hepatocyte apoptosis.MethodsIn vitro studies utilized Clone9 hepatocytes treated with PA to simulate FLD conditions. The effects of CM ethyl acetate extract (EAECM) on apoptosis, mitochondrial function, ER stress, inflammation, and oxidative stress were evaluated. In vivo experiments involved FVB mice fed a NASH diet containing high levels of PA to induce FLD, with powdered CM administered orally to assess its impact on body weight, fasting blood glucose level, liver health, fibrosis, and markers of ER stress, inflammation, and oxidative stress.ResultsEAECM demonstrated protective effects against PA-induced apoptosis, mitochondrial dysfunction, ER stress, inflammation, and oxidative stress in vitro. In vivo, powdered CM supplementation attenuated body weight gain, improved fasting blood glucose level, prevented hepatomegaly, reduced serum triglycerides, and inhibited liver fibrosis. Furthermore, powdered CM treatment mitigated ER stress, inflammation, and oxidative stress in the liver of mice receiving a NASH diet.ConclusionC. militaris holds promise as a therapeutic agent for FLD, as evidenced by its ability to alleviate PA-induced hepatocytes damage and hinder FLD progression in mice. Further research is warranted to identify the active compounds responsible for its beneficial effects and to explore its potential clinical applications in treating FLD.
High-risk adverse events in two types of single inhaler triple-therapy: a pharmacovigilance study based on the FAERS database
Authors: Ruan Zhishen , Wang Chunbin , Yuan Shasha , Fan Yiling , Xu Bo , Cong Xiaodong , Li Dan , Miao Qing 
Published: January 2025

ObjectiveSingle inhaler triple therapy is widely used in Chronic Obstructive Pulmonary Disease (COPD) and asthma. This research aimed to analyze adverse events (AEs) associated with Budesonide/Glycopyrronium/Formoterol Fumarate (BUD/GLY/FOR) and Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI).MethodsThis is a cross-sectional study. BUD/GLY/FOR (2020Q3-2024Q3) and FF/UMEC/VI (2018Q1-2024Q3) report files were downloaded from the U.S. Food and Drug Administration’s (FDA) Adverse Event Reporting System (FAERS) database. We use reporting odds ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural network (BCPNN) for disproportionality analysis. The aim was to explore associations between drugs and preferred term (PT) and system organ classification (SOC) levels. We focused on exploring the top 10 PTs of each drug’s BCPNN (IC) effect value and the PT of pneumonia.Results16,355 AEs in BUD/GLY/FOR and 39,110 AEs in FF/UMEC/VI were extracted. Device use issues, oropharyngeal and vocal problems, pneumonia, candida infections, and urinary retention were the standard PTs present in drug leaflets. The risk of device use issues was higher in BUD/GLY/FOR, whereas the risk of pneumonia and candida infection in FF/UMEC/ VI had higher risk. Outside of the drug leaflets, both drugs were associated with a higher risk of AEs in vascular disorders. BUD/GLY/FOR group had a higher risk of AEs in body height decreased and hypoacusis. Notably, this study found an association between the above PTs and drugs, and the causal relationship needs to be verified by further longitudinal studies.ConclusionOur study provides a preliminary exploration of the safety of clinical use of BUD/GLY/FOR and FF/UMEC/VI, and clinicians should be alert to potential adverse effects.
Targeted lipidomics analysis of possible molecular mechanisms of lipid changes in temporal lobe epilepsy models
Authors: Sun Huaiyu , Li Xuewei , Chen Zhiqing , Meng Hongmei 
Published: January 2025

BackgroundLipids are vital biomolecules involved in the formation of various biofilms. Seizures can cause changes in lipid metabolism in the brain. In-depth studies at multiple levels are urgently needed to elucidate lipid composition, distribution, and metabolic pathways in the brain after seizure.MethodsIn this research, a cutting-edge targeted quantitative lipidomics study was conducted on the hippocampal tissues of six rats with temporal lobe epilepsy and six normal rats. Accurate lipid quantification based on linear equations was calculated using an internal standard. The lipids were quantitatively and qualitatively analyzed by ultra-high performance liquid chromatography (UPLC) and mass spectrometry (MS).ResultsA total of 21 lipid classes were identified. Among them, the most abundant were triacylglycerol (TG), phosphatidyl ethanolamine (PE-P), and fatty acids (FA). Cholesteryl ester (ChE) exhibits the most considerable difference between the normal and epileptic samples. ChE was found to be the most significantly upregulated lipid, while FA was observed to be the most significantly downregulated lipid.ConclusionBased on the absolute quantitative analysis of lipids in rat hippocampal specimens, the contents and change trends of different lipids were observed. Upregulation of ChE and dihydroceramide (DHCer) was observed, and an analysis of the distribution changes elucidated the causes and possible molecular mechanisms of lipid accumulation in temporal lobe epilepsy. The results and methods described provide a comprehensive analysis of lipid metabolism in temporal lobe epilepsy and a new therapeutic target for the treatment of epilepsy.
Acute effects of proprioceptive neuromuscular facilitation stretching on rectus femoris muscle stiffness: a dose-response shear-wave elastography study
Authors: Kranjc Sara , Fink Mojca , Nakamura Masatoshi , Kozinc Žiga 
Published: January 2025

IntroductionProprioceptive neuromuscular facilitation (PNF) stretching is widely used to increase range of motion, but its underlying mechanisms are not well understood. This experimental, parallel group design study investigated the acute effects of PNF stretching on rectus femoris muscle stiffness and explored a potential dose-response relationship.MethodsThirty healthy young adults (23 females, 7 males) were randomly assigned to either a PNF stretching group (n = 15; 22.96 ± 2.2 years) or a control group (n = 15; 23.3 ± 2.1 years). Rectus femoris stiffness was measured using shear-wave elastography (Resona 7, Mindray, China) at two locations (distal and proximal) before and after the second, fourth, and sixth sets of PNF stretching. The protocol involved six sets, each with three 10-s stretches and 5-s maximal contractions.ResultsThe results indicate that PNF stretching had no statistically significant effect on muscle stiffness, with no main effects of group (F = 0.05; p = 0.830) or time (F = 0.545; p = 0.653), and no significant interactions. However, the proximal location showed a substantially higher shear modulus compared to the distal location (F = 63.6; p &lt; 0.001; η2 = 0.69), independent of group or time.DiscussionThese findings highlight a location-specific difference in muscle stiffness that was unaffected by the intervention. In conclusion, PNF stretching did not acutely reduce rectus femoris stiffness compared to passive rest, regardless of the number of stretching sets performed. Further research is needed to understand the muscle-specific effects of PNF stretching.