bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioinformatic characterization of STING expression in hematological malignancies reveals association with prognosis and anti-tumor immunity
Authors: Wen Xiang-mei , Xu Zi-jun , Ma Ji-chun , Zhang Min-jie , Jin Ye , Lin Jiang , Qian Jun , Fang Yuan-yuan , Luo Shu-yu , Mao Zhen-wei 
Published: February 2025

IntroductionStimulator of interferon response cGAMP interactor (STING) is essential for both innate and adaptive immunity. However, a comprehensive molecular characterization of STING expression across hematological malignancies is lacking.MethodsIn this study, the pan-blood-cancer landscape related to STING expression was identified using the GTEx, CCLE, Hemap, and TCGA databases, and the potential value for predicting prognosis was investigated. The relationship between STING expression and immune cell enrichment was assessed in the Hemap database. Moreover, the value of STING in predicting the efficacy of immunotherapy was validated using tumor immune dysfunction and exclusion (TIDE) biomarkers and real-world immunotherapy datasets.Results and DiscussionSTING was found to be relatively highly expressed in acute myeloid leukemia (AML) and chronic myeloid leukemia, with higher STING expression correlated with poorer prognosis in AML. STING expression was positively correlated with immune-related pathways such as IFN-gamma response, IFN-alpha response, and inflammatory response. Cytolytic score and STING expression were positively correlated in some hematological tumors, especially chronic lymphocytic leukemia and mantle cell lymphoma. Interestingly, STING expression was negatively correlated with TIDE biomarkers in AML, suggesting that AML patients with a high STING expression level may benefit from immunologic treatment. Our findings contribute a molecular characterization of STING across hematological malignancies, facilitating the development of individualized prognosis and treatment strategies.
Sequence-structure based prediction of pathogenicity for amino acid substitutions in proteins associated with primary immunodeficiencies
Authors: Porfireva Ekaterina S. , Zadorozhny Anton D. , Rudik Anastasia V. , Filimonov Dmitry A. , Lagunin Alexey A. 
Published: February 2025

IntroductionPrimary immunodeficiencies (PIDs) are a group of rare genetic disorders characterized by dysfunction of the immune system components. Early diagnosis and treatment are essential to prevent severe or life-threatening complications. PIDs are manifested by diverse clinical symptoms, posing challenges for accurate diagnosis. A key aspect of PID diagnosis is identifying specific amino acid substitutions in the proteins related with heritable diseases. In this study, we have developed classification sequence-structure-property relationships (SSPR) models for predicting the pathogenicity of amino acid substitutions (AAS) in 25 proteins associated with the most important and genetically studied PIDs and encoded genes: IL2RG, JAK3, RAG1, RAG2, ADA, DCLRE1C, CD40LG, WAS, ATM, STAT3, KMT2D, BTK, FOXP3, AIRE, FAS, ELANE, ITGB2, CYBB, G6PD, GATA2, STAT1, IFIH1, NLRP3, MEFV, and SERPING1.MethodsThe data on 4825 pathogenic and benign AASs in the selected proteins were extracted from ClinVar and gnomAD. SSPR models were created for each protein using the MultiPASS software based on the Bayesian algorithm and different levels of MNA (Multilevel Neighborhoods of Atoms) descriptors for the representation of structural formulas of protein fragments including AAS.ResultsThe accuracy of prediction was assessed through a 5-fold cross-validation and compared to other bioinformatics tools, such as SIFT4G, Polyphen2 HDIV, FATHMM, MetaSVM, PROVEAN, ClinPred, and Alpha Missense. The best SSPR models demonstrated high accuracy, with an average ROC AUC of 0.831 ± 0.037, a Balanced accuracy of (0.763 ± 0.034), MCC (0.457 ± 0.06), and F-measure (0.623 ± 0.07) across all genes, outperforming the most popular bioinformatics tools.ConclusionsThe best created SSPR models for the prediction of pathogenicity of amino acid substitutions related with PIDs have been implemented in a freely available web application SAV-Pred (Single Amino acid Variants Predictor, http://www.way2drug.com/SAV-Pred/), which may be a useful tool for medical geneticists and clinicians. The use of SAV-Pred for some clinical cases of PIDs are provided.
IFNβ drives ferroptosis through elevating TRIM22 and promotes the cytotoxicity of RSL3
Authors: Dong Huiyue , Zhu Ling , Sun Jingjing , Chen Qiuyan , Liu Pengyang , Zhang Wei , Zeng Huajing , Lin Rong , Yu Zongyang , Lu Jun 
Published: February 2025

BackgroundCyclic GMP-AMP synthase (cGAS)-stimulator-of-interferon genes (STING) pathway is a cytosolic DNA sensor system. The production of this pathway, interferon-β (IFNβ), could suppress the growth of tumor cells, yet it is unclear whether ferroptosis is involved in IFNβ-induced cell death.MethodsThe effects of IFNβ on ferroptosis were analyzed in HT1080, 4T1, HCT116 and 786-O cells. HT1080 and 4T1 cells treated with IFNβ were subjected to RNA-Seq analysis. STAT1, STAT3, TRIM21, and TRIM22 were silenced by siRNAs to examine their effects on IFNβ-induced ferroptosis. The cGAS-STING signaling pathway-activated mice were used to evaluate the effects of IFNβ on ferroptosis in vivo. HT1080 cells, three-dimensional (3D) spheroids, and the xenograft mouse models were treated with IFNβ, RSL3, or IFNβ combination with RSL3 to analyze whether IFNβ enhances RSL3-induced ferroptosis.ResultsHere, we found that IFNβ could promote intracellular Fe2+ and lipid peroxidation levels, and decrease GSH levels in tumor cells. RNA sequencing data revealed that IFNβ induced a transcriptomic disturbance in ferroptosis-related genes. Knockdown of tripartite motif-containing 22 (TRIM22) suppressed the levels of intracellular Fe2+ and lipid ROS. It also reduced heme oxygenase (HMOX1) protein levels and increased ferroptosis suppressor protein 1 (FSP1) levels in HT1080 cells treated with IFNβ. Furthermore, our results illustrated that IFNβ enhanced the RAS-selective lethal 3 (RSL3)-induced ferroptosis and the inhibitory effect of RSL3 on GPX4. Meanwhile, compared to the groups treated with either IFNβ or RSL3 alone, the combination treatment of IFNβ and RSL3 significantly inhibited the growth of HT1080 three-dimensional (3D) spheroids and tumor in a mouse xenograft model.ConclusionsOur work reveals a role for IFNβ in promoting ferroptosis and provides evidence that IFNβ could be used with RSL3 to increase cytotoxic effects in tumor cells.
Development and assessment of an intestinal tri-cellular model to investigate the pro/anti-inflammatory potential of digested foods
Authors: Ramal-Sanchez Marina , Bravo-Trippetta Chiara , D’Antonio Veronica , Corvaglia Elena , Kämpfer Angela A. M. , Schins Roel P. F. , Serafini Mauro , Angelino Donato 
Published: February 2025

IntroductionImmunonutrition, defined as the potential of foods, nutrients and dietary patterns to modulate the immune system activity, has been proposed as a strategy to enhance the immune response in both metabolic and immune-mediated diseases. However, the anti-/pro-inflammatory role of foods and diets is far to be fully ascertained, and thus there is a continued needed for appropriate in vitro cell-culture models to investigate the role of foods in modulating cell-mediated inflammatory processes. This study aims to develop and test an in vitro tri-culture model, simulating the complexity of the intestinal tract and its multiple cell interactions.MethodsTo achieve this, the intestinal epithelial barrier was established by co-culturing human Caco-2 enterocyte-like and HT29-MTX-E12 mucus producing goblet-like colon cells, then adding human monocyte THP-1 cells to the basolateral compartment. The integrity and stability of the epithelial barrier were monitored and the inflammatory response of the model was assessed using various stressors at different concentrations, both individually and in combination (phorbol-12- myristate-13-acetate or PMA, and lipopolysaccharide or LPS), in terms of cytokines production. To test the model, different concentrations of in vitro digested broccoli (BD) were added to the apical section of the model.ResultsSupernatants from the basolateral compartment were collected and analyzed for cytokines production (IL-6, TNF-α, IL-12p70, IL-18 and IL-8) using automated ELISA (ELLA). Additionally, ZO-1 protein from the tight junctions of epithelial cells was analyzed by flow cytometry. The results indicated that 100 nM PMA added to the whole model for 20 h was the best stressor to simulate a mild-inflammatory status of the gut. Following treatment with BD, IL-6, TNF-α, IL-8 and IL-18 were significantly reduced compared to the control group, while ZO-1 expression increased at the lowest BD concentration.ConclusionsThese findings confirm the feasibility of the model for assessing the effects of food digesta on specific cytokines and permeability markers, representing a valuable strategy for investigating the role of foods in modulating the inflammatory response. The results obtained may support dietary strategies aimed at promoting wellbeing and preventing inflammatory-related metabolic diseases.
Impact of anthropogenic activities on the biodiversity of macrobenthos and benthic ecological quality in the mudflats of Hwangdo Island, South Korea: field surveys and remote sensing assessments
Authors: Liang Jian , Ma Chae-Woo 
Published: February 2025

IntroductionAs coastal urbanization progresses, anthropogenic activities have significantly impacted mudflats. In South Korea, land reclamation and aquaculture have drastically altered mudflat ecosystems.MethodsIn our study, we utilized five remote sensing indices to assess the impact of anthropogenic activities on Hwangdo Island. We supplemented this with field surveys to evaluate macrobenthic biodiversity and benthic ecological quality, investigating their relationship to anthropogenic activities.Results and discussionSpearman’s correlation analysis revealed that terrestrial ecological quality influences macrobenthic biodiversity. The abundance of the predominant species, Pirenella sp., was primarily influenced by normalized differential build-up and bare soil index (NDBSI). Furthermore, biota-environment matching (BIO-ENV) analysis, distance-based multivariate analysis for a linear model (DisLM), and distance-based redundancy analysis (dbRDA) all pinpointed NDBSI as the predominant factor impacting macrobenthic communities in the mudflats of Hwangdo Island. Seasonal changes in NDBSI were mainly attributed to variations in bare soil area resulting from agricultural activities on Hwangdo Island. Overall, macrobenthic communities in the mudflats of Hwangdo Island are mainly indirectly affected by agricultural activities. Moreover, our study offers a fresh perspective on the conservation of Hwangdo Island’s mudflats and provides critical references for the South Korean government in crafting and implementing mudflat protection policies.
Case report: The value of early application of mNGS technology in the diagnosis and treatment of severe Legionnaires’ disease: reports of two cases with different outcomes
Authors: Fang Jianqing , Wang Zhe , Shen Yu , Wu Xuenong , Fang Hao , Sun Xiaokui , Yu Ting , Zhang Qingqing 
Published: February 2025

BackgroundLegionnaires’ disease has a high clinical mortality rate, and early diagnosis and treatment are critical. Increasing evidence shows that metagenomic next-generation sequencing (mNGS) has excellent potential for the early identification of pathogens. To help clinicians better recognize Legionnaires’ disease in its early stage and to illustrate the diagnostic value of mNGS technology, we reviewed and summarized two cases of severe Legionnaires’ disease.Methods and analysisWe selected two patients with severe Legionnaires’ disease who were admitted to our department in recent years. We discuss experience with them and the shortcomings in their treatment by summarizing their medical history, disease evolution, tests, and diagnostic and therapeutic processes.ResultsIn both patients, the diagnosis of Legionnaires’ disease was confirmed through analysis of the bronchoalveolar lavage fluid (BALF). The middle-aged male patient was cured and discharged due to early detection and diagnosis. The elderly immunocompromised patient died due to a delay in diagnosis.ConclusionThis study highlights the importance of the early recognition and diagnosis of severe Legionnaires’ disease and the advantages of mNGS in identifying the pathogen.
Association of dietary niacin intake with osteoporosis in the postmenopausal women in the US: NHANES 2007–2018
Authors: Li Li , Liang Wankun , Deng Bing , Jiang Yue , Huang Xiaomin , Zhang Yanlin , Lu Tianrui , Wang Lu , Xu Yunxiang , Chen Guizhen 
Published: February 2025

BackgroundElderly individuals with inadequate vitamin B level are at increased risk of degenerative conditions, notably cardiovascular disorders, cognitive impairments, and osteoporosis. The relationship between niacin (vitamin B3) consumption and osteoporosis risk remains a subject of debate. This study aimed to clarify the relationship between dietary niacin intake and the incidence of osteoporosis in postmenopausal women aged ≥50 years.MethodsIn this study, we gathered details on participants’ bone mineral density, osteoporosis status, dietary niacin intake, and several other critical variables. Multivariate logistic regression models were constructed to determine the association between dietary niacin intake and the incidence of osteoporosis. Restricted cubic splines were employed to further assess the linearity and explore the shape of the dose-response associations. Additionally, we performed stratified and interaction analyses to illustrate the stability of the observed relationships across different subgroups.ResultsAfter adjusting for all covariates, there was a significant inverse association with osteoporosis (OR = 0.87; 95% CI: 0.77–0.97; p = 0.016). A negative relationship was observed between dietary niacin intake and the risk of osteoporosis (nonlinear: p = 0.672). While stratified analyses revealed some differences in the association between dietary niacin intake and osteoporosis risk, these differences were not statistically significant.ConclusionDietary niacin intake exhibited an inverse correlation with the incidence of osteoporosis. The risk of osteoporosis was significantly reduced by 13% with every 10 mg/day increase in daily dietary niacin consumption among postmenopausal women.
Does quercetin affect tendon healing? An experimental study in a rat model of Achilles tendon injury
Authors: Yurteri Ahmet , Mercan Numan , Çelik Zeliha Esin , Yaykaşlı Hakan , Yıldırım Ahmet 
Published: February 2025

PurposeThe objective of this study was to investigate the impact of quercetin, a potent antioxidant, on tendon healing utilizing a rat Achilles tendon injury model.Materials and methodsThe study involved 32 male Wistar-Albino rats, randomly split into experimental (quercetin) and control groups, each with 16 rats. A bilateral Achilles tenotomy model was applied, with the experimental group receiving quercetin and the control group receiving corn oil via oral gavage from surgery until sacrifice. One Achilles tendon per rat underwent histopathological and immunohistochemical evaluations, while the other underwent biomechanical analysis.ResultsTendons were evaluated histopathologically in terms of tenocyte, ground substance, collagen, and vascularity, and quercetin was observed to significantly increase tendon healing in the experimental group (p-values = 0.0232, 0.0128, 0.0272, 0.0307, respectively). In the immunohistochemical analysis, type I collagen, type III collagen, alpha smooth muscle actin (SMA), and Galectin-3 were evaluated, and it was observed that quercetin increased tendon healing (p-values = 0.0166, 0.0036, 0.0323, 0.0295, respectively). In the biomechanical analysis, the rupture strength was evaluated with six parameters (failure load, maximum energy, displacement, stiffness, ultimate stress, and strain), and it was observed that quercetin significantly increased the rupture strength (p-values = 0.032, 0.014, 0.026, 0.025, 0.045, 0.012, respectively).ConclusionQuercetin significantly enhanced tendon healing both biomechanically and immunohistochemically. However, further clinical studies are needed to understand its effects on human tendon healing, as this is the first study of its kind.
Impact of pre-pregnancy body mass index on preeclampsia
Authors: Mao Jing , Sun Hanxiang , Shen Qinxin , Zou Chang , Yang Yuanyuan , Du Qiaoling 
Published: February 2025

BackgroundIt remains unclear how pre-pregnancy body mass index (BMI) affects preeclampsia in the Chinese population, primarily due to insufficient large-scale research on this topic.ObjectiveThe study aimed to determine the relationship between pre-pregnancy BMI and (severe) preeclampsia in the Chinese population, providing a detailed description of the findings.MethodsThe retrospective study included a total of 75,773 pregnant women registered between 2016 and 2020. These participants were categorized into four groups based on their pre-pregnancy BMI: underweight (BMI &lt; 18.5 kg/m2), normal weight (BMI 18.5–&lt;24 kg/m2), overweight (BMI 24–&lt;28 kg/m2), and obese (BMI ≥ 28 kg/m2). The relationship between risks of preeclampsia or severe preeclampsia and pre-pregnancy BMI were further explored, with an evaluation of potential modification by maternal age.ResultsA lower risk of developing preeclampsia was observed in the underweight population, with an OR of 0.604 (95%CI, 0.507–0.719). In contrast, women who were overweight or obese during the pre-pregnancy period demonstrated a significantly higher risk of preeclampsia, with ORs of 2.211 (95%CI, 1.967–2.486) and 3.662 (95%CI, 3.026–4.431), respectively. After adjusting for confounding factors, the elevated risk of preeclampsia persisted, showing ORs of 2.152(95%CI, 1.911–2.425) for the overweight population and 3.493 (95%CI, 2.874–4.245) for those who were obese, while the risk for underweight women remained lower, with an OR of 0.609(95%CI, 0.511–0.727). For severe preeclampsia, the risk was also higher in the overweight and obese participants after adjusting for confounders, demonstrating ORs of 1.652(95%CI, 1.364–2.001) and 2.762(95%CI, 2.014–3.788), respectively. The underweight population exhibited a lower risk of severe preeclampsia, with an OR of 0.720(95%CI, 0.565–0.919). In addition, these risks were not significantly associated with maternal age.ConclusionRegardless of adjustment for confounders, underweight women demonstrated a lower risk of preeclampsia, whereas the overweight/obese population exhibited a higher occurrence of both preeclampsia and severe preeclampsia. These associations were not influenced by maternal age.
Multidrug resistance of Pseudomonas aeruginosa: do virulence properties impact on resistance patterns?
Authors: Saha Poulomi , Kabir Rubaiya Binte , Ahsan Chowdhury Rafiqul , Yasmin Mahmuda 
Published: February 2025

IntroductionPatients with nosocomial infections are at risk of multidrug-resistant (MDR) Pseudomonas aeruginosa since these bacteria slow down the entire treatment process, increasing the morbidity and mortality of patients staying in hospital. The purpose of the research was to assess the simultaneous presence of multidrug resistance and virulence factors among nosocomial strains of P. aeruginosa to evaluate significant association among them.MethodsOne hundred and eight clinical isolates of P. aeruginosa were found in a variety of samples taken from patients having nosocomial infection, including wound swabs, pus, sputum, tracheal aspirate, and urine. An antibiogram was performed to investigate the pathogen’s antibiotic sensitivity pattern against 14 widely used antibiotics in Bangladesh. Virulence factors were evaluated, and the presence of ten β-lactamase and six virulence genes was analyzed by performing PCR. By using a binary logistic regression test with a 95% confidence interval, the relationship between MDR phenotypes and the virulence attributes was assessed.ResultsThe susceptibility rate among the isolates was 70–75% for aminoglycosides (amikacin, gentamicin, netilmicin), 15–20% for cephalosporins (ceftazidime, ceftriaxone), 30–35% for quinolones (ciprofloxacin, levofloxacin), 10–15% for tetracyclines (tigecycline, doxycycline), 15–20% for carbapenem (meropenem), 10–15% for sulfonamide (co-trimoxazole), 5–10% for amoxiclav, and 30–35% for piperacillin/tazobactam. A total of 74.1% of the strains carried metallo-β-lactamase (MBL) genes. Among the isolates, 89% showed hemolytic activity, 80–90% produced different pigments such as fluorescein and pyoverdine, 46% were strong biofilm producers, and all the isolates presented different types of motilities (swimming, swarming, and twitching). The virulence genes (lasB, exoS, toxA, aprA, algD, and plcH) were detected within a range of 60–80% of the isolates.DiscussionOnly the toxA gene and twitching motility showed a significant correlation (p-value = 0.001 and 0.028, respectively) with multidrug resistance in the clinical P. aeruginosa isolates which indicates that it can be used as a drug target to combat these organisms. The high prevalence of MDR strains and their association with virulence factors revealed the potential of the pathogen to cause an infection. The current study advocates for immediate epidemiological surveillance of MDR P. aeruginosa strains in Bangladesh to impede the rapid dissemination of this opportunistic pathogen.
Genomic characterization and evolutionary analysis of a Getah virus variant from piglets in central China
Authors: Guo Zhenhua , Jiang Yao , Li Peng , Zhang Gaiping 
Published: February 2025

IntroductionAs a re-emerging mosquito-borne virus, Getah virus (GETV) has been found in more than 10 countries surrounded by the Pacific Ocean and shows a broadly host tropism, raising concerns for the potential risk to public health. Horses and pigs are susceptible to GETV and play pivotal roles to the GETV adaptive evolution.MethodsHere, we reported a GETV outbreak in a pig farm with 20% suckling piglets losses. The genomic characteristics and evolutionary relationship of the pathogenic viral strain were also analyzed.ResultsThe isolate GETV-HeN202309 shared the highest nucleotide identity of 99.8% with strains from Guangdong and Sichuan province, suggesting it is an imported transmission. Although the phylogenetic analysis divided GETV into four groups (groups I–IV), only strains in group III were dominant and widely circulating in the fields. Furthermore, several amino acid substitutions in E2 protein were identified among different GETV groups and the substitution at D262th N site led to an additional glycosylation modification. Besides, six amino acid sites were under positive selection of E2 protein. Most of these special sites were distributed in domain A, B, and C of E2 protein, which are usually associated with the GETV infection and immune response.DiscussionOur study expands knowledge of GETV pathogenicity and deepens understanding of GETV genetic and adaptive evolution, which would be valuable for the development of diagnosis and prevention for GETV.