bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study on the inhibition activity and mechanism of Tanreqing against Klebsiella pneumoniae biofilm formation in vitro and in vivo
Authors: Zhang Wenxia , He Min , Kong Nana , Niu Yuxiao , Li Anhong , Yan Yuzhong 
Published: April 2024

ObjectiveTo evaluate the antibacterial effect of Tanreqing (TRQ) against K. pneumoniae and its inhibition activity on bacterial biofilm formation in vitro and in vivo, and to explore the mechanism of the inhibitory effects of TRQ on K. pneumoniae biofilm formation.MethodsAn in vitro biofilm model of K. pneumoniae was established, and the impact of TRQ on biofilm formation was evaluated using crystal violet staining and scanning electron microscopy (SEM). Furthermore, the clearance effect of TRQ against K. pneumoniae in the biofilm was assessed using the viable plate counting method; q-RT PCR was used to evaluate the inhibitory effect of different concentrations of TRQ on the expression of biofilm-related genes in Klebsiella pneumoniae; The activity of quorum sensing signal molecule AI-2 was detected by Vibrio harveyi bioluminescence assay; Meanwhile, a guinea pig lung infection model of Klebsiella pneumoniae was constructed, and after treated with drugs, pathological analysis of lung tissue and determination of bacterial load in lung tissue were performed. The treatment groups included TRQ group, imipenem(IPM) group, TRQ+IPM group, and sterile saline group as the control.ResultsThe formation of K. pneumoniae biofilm was significantly inhibited by TRQ in vitro experiments. Furthermore, when combined with IPM, the clearance of K. pneumoniae in the biofilm was notably increased compared to the TRQ group and IPM group alone. q-RT PCR analysis revealed that TRQ down-regulated the expression of genes related to biofilm formation in K. pneumoniae, specifically luxS, wbbm, wzm, and lsrK, and also inhibited the activity of AI-2 molecules in the bacterium. In vivo experiments demonstrated that TRQ effectively treated guinea pig lung infections, resulting in reduced lung inflammation. Additionally, when combined with IPM, there was a significant reduction in the bacterial load in lung tissue.ConclusionTRQ as a potential therapeutic agent plays a great role in the treatment of K. pneumoniae infections, particularly in combination with conventional antibiotics. And TRQ can enhanced the clearance effect on the bacterium by inhibiting the K. pneumoniae biofilm formation, which provided experimental evidence in support of clinical treatment of TRQ against K. pneumoniae infections.
Second booster dose improves antibody neutralization against BA.1, BA.5 and BQ.1.1 in individuals previously immunized with CoronaVac plus BNT162B2 booster protocol
Authors: Campos Guilherme R. F. , Almeida Nathalie Bonatti Franco , Filgueiras Priscilla Soares , Corsini Camila Amormino , Gomes Sarah Vieira Contin , de Miranda Daniel Alvim Pena , de Assis Jéssica Vieira , Silva Thaís Bárbara de Souza , Alves Pedro Augusto , Fernandes Gabriel da Rocha , de Oliveira Jaquelline Germano , Rahal Paula , Grenfell Rafaella Fortini Queiroz , Nogueira Maurício L. 
Published: April 2024

IntroductionSARS-CoV-2 vaccines production and distribution enabled the return to normalcy worldwide, but it was not fast enough to avoid the emergence of variants capable of evading immune response induced by prior infections and vaccination. This study evaluated, against Omicron sublineages BA.1, BA.5 and BQ.1.1, the antibody response of a cohort vaccinated with a two doses CoronaVac protocol and followed by two heterologous booster doses.MethodsTo assess vaccination effectiveness, serum samples were collected from 160 individuals, in 3 different time points (9, 12 and 18 months after CoronaVac protocol). For each time point, individuals were divided into 3 subgroups, based on the number of additional doses received (No booster, 1 booster and 2 boosters), and a viral microneutralization assay was performed to evaluate neutralization titers and seroconvertion rate. ResultsThe findings presented here show that, despite the first booster, at 9m time point, improved neutralization level against omicron ancestor BA.1 (133.1 to 663.3), this trend was significantly lower for BQ.1.1 and BA.5 (132.4 to 199.1, 63.2 to 100.2, respectively). However, at 18m time point, the administration of a second booster dose considerably improved the antibody neutralization, and this was observed not only against BA.1 (2361.5), but also against subvariants BQ.1.1 (726.1) and BA.5 (659.1). Additionally, our data showed that, after first booster, seroconvertion rate for BA.5 decayed over time (93.3% at 12m to 68.4% at 18m), but after the second booster, seroconvertion was completely recovered (95% at 18m). DiscussionOur study reinforces the concerns about immunity evasion of the SARS-CoV-2 omicron subvariants, where BA.5 and BQ.1.1 were less neutralized by vaccine induced antibodies than BA.1. On the other hand, the administration of a second booster significantly enhanced antibody neutralization capacity against these subvariants. It is likely that, as new SARS-CoV-2 subvariants continue to emerge, additional immunizations will be needed over time.
Serum MMP-8 and TIMP-1 concentrations in a population-based cohort: effects of age, gender, and health status
Authors: Ranta Julia , Havulinna Aki S. , Tervahartiala Taina , Niemi Katriina , Aarabi Ghazal , Vihervaara Terhi , Salomaa Veikko , Sorsa Timo , Pussinen Pirkko J. , Salminen Aino 
Published: April 2024

BackgroundMatrix-degrading proteinases and their regulators, such as matrix metalloproteinase 8 (MMP-8) and tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), may contribute to various pathological events. Elevated MMP-8 concentrations have been associated with e.g., cardiovascular diseases and periodontitis. However, there is little knowledge on the physiological concentrations of these molecules in serum, or the effect of demographic or lifestyle factors on their levels.Design and methodsWe investigated the effect of various demographic characteristics and behavioral habits, such as aging, sex, smoking, and BMI, on serum concentrations of MMP-8 and TIMP-1. We used the FINRISK97 cohort (n = 8,446), which has comprehensive information on demographic and lifestyle factors, clinical data, laboratory measurements, and register data available. Further, we investigated the concentrations of MMP-8, TIMP-1, and the MMP-8/TIMP-1 ratio in different age groups of healthy and diseased participants. A t-test was used to compare log-transformed mean levels in different groups and linear regression was used to evaluate the association between MMP-8 and TIMP-1 and selected diseases and background variables.ResultsMMP-8 levels decreased with increasing age in the whole population and for women, while TIMP-1 concentration increased slightly with age for the whole population and both genders separately (p for linear trend &lt;0.001). The concentrations of MMP-8 were lower and TIMP-1 higher in men compared to women (p &lt; 0.001). Additionally, a significant positive association was found for MMP-8 and smoking, CRP, and an inverse association with obesity and fasting time. For TIMP-1, significant positive associations were found with smoking, CRP and obesity, and an inverse association with prevalent diabetes.ConclusionThe association of serum MMP-8 and TIMP-1 concentrations with cardiometabolic risk is frequently investigated. MMP-8 levels decrease significantly with age and fasting time. In addition, sex, smoking, and obesity are associated with both MMP-8 and TIMP-1 concentrations. These factors should be carefully considered in epidemiological studies on serum MMP-8 and TIMP-1.
Teachers’ perceptions of the barriers to STEM teaching in Qatar’s secondary schools: a structural equation modeling analysis
Authors: Sellami Abdellatif , Santhosh Malavika , Bhadra Jolly , Ahmad Zubair 
Published: April 2024

IntroductionEducators play a pivotal role in shaping students’ academic achievements, particularly in STEM (science, technology, engineering, and mathematics) fields. The instructional techniques employed by teachers significantly impact students’ decisions to pursue or persist in STEM disciplines. This research aims to explore the challenges faced by high school STEM teachers in Qatar in delivering effective STEM instruction.MethodsData was collected through a survey administered to 290 high school STEM teachers across thirty-nine schools in Qatar. The survey targeted teachers in the 11th and 12th grades. Structural Equation Modeling (SEM) was utilized to analyze the data and examine teachers’ perceived barriers to effective STEM instruction.ResultsThe findings revealed various barriers hindering STEM instruction. These barriers were categorized into school-related, student-related, technology-related, and teaching-related factors. All the hypothesized teaching barriers [i.e., (student-related: β = –0.243, p &lt; 0.001); (school-related: β = –0.122, p &lt; 0.001), (technologyrelated: β = –0.123, p = 0.040); and (instruction-related: β = –0.112, p &lt; 0.018)] were negatively related to teachers’ STEM teaching. Among the various obstacles, it appears that the most formidable challenges for high school STEM teachers are related to students (β = –0.243, p &lt; 0.001).DiscussionUnderstanding these barriers is crucial for informing educational policies and developing strategies to enhance STEM learning in Qatar’s high schools. Addressing these barriers is essential to provide adequate resources, professional development opportunities, and support systems. By addressing these challenges, Qatar can foster a conducive environment for effective STEM instruction, thereby nurturing a future generation of STEM professionals.
Causal associations between autoimmune diseases and sarcopenia-related traits: a bi-directional Mendelian randomization study
Authors: Chen Chunlan , He Ying 
Published: April 2024

Background:Sarcopenia is common in patients with autoimmune diseases (ADs); however, the causal associations between ADs and sarcopenia remain unclear. Therefore, this study investigated the causal associations using bi-directional Mendelian randomization analysis.Methods:Exposure-related single-nucleotide polymorphisms (SNPs) were extracted from genome-wide association studies (GWASs). GWAS statistics for common ADs [Crohn’s disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriasis (PSO), and multiple sclerosis (MS)] and sarcopenia-related traits [hand grip strength (HGS), appendicular fat-free mass (FFM), and walking pace] were obtained from public datasets. Inverse-variance weighting as the main method was used to evaluate the causal effect.Results:Genetically predicted CD had causal effects on whole-body FFM (β = −0.005, p = 0.001), leg FFM (βleft = −0.006, p = 1.8E-4; βright = −0.007, p = 2.0E-4), and arm FFM (βleft = −0.005, p = 0.005; βright = −0.005, p = 0.001), while RA had causal effects on 8 sarcopenia-related traits, namely, HGS (βleft = −2.06, p = 2.8E-38; βright = −2.311, p = 2E-20), whole-body FFM (β = −0.842, p = 4.7E-10), leg FFM (βleft = −0.666, p = 2.6E-6; βright = −0.073, p = 2.1E-3), arm FFM (βleft = −0.63, p = 4.4E-6; βright = −0.736, p = 4.4E-8), and walking pace (β = −1.019, p = 6.2E-14). In the reverse direction, HGS (odds ratio [OR]left = 10.257, p = 3.6E-5; ORright = 16.445, p = 3.7E-7) had causal effects on CD, while HGS (ORleft = 0.994, p = 0.004; ORright = 0.993, p = 1.4E-4), leg FFM (ORleft = 1.003, p = 0.005; ORright = 1.005, p = 1.9E-4), and walking pace (OR = 0.985, p = 5.7E-5) were causally associated with RA. No evidence showed causal associations of UC, SLE, PSO, or MS with sarcopenia-related traits.Conclusion:Our study demonstrated that the genetic susceptibility to CD and RA was associated with high risk of sarcopenia, and some sarcopenia-related traits had causal effects on CD or RA.
Evaluating the causal association between bronchiectasis and different types of inflammatory bowel disease: a two-sample Mendelian randomization study
Authors: Zeng Qian , Hu Da , Li Yuan , Zhou Zhiwei , Wu Jinfeng , Li Xiaodong , Yu Xiqiu 
Published: April 2024

Background and objectivesPrevious observational studies have established a connection between bronchiectasis and inflammatory bowel disease (IBD), but none of these studies have provided a clear explanation for the underlying cause of this relationship. The present study thus implemented Mendelian randomization (MR) design to explore possible bidirectional relationships between IBD and bronchiectasis risk, with an additional focus on Crohn’s disease (CD) and ulcerative colitis (UC) as IBD subtypes.Materials and methodsA large genome-wide association study (GWAS)-derived data pool was leveraged to examine the relationships between bronchiectasis and IBD, CD, and UC. Two-sample MR analyses were performed with an inverse variance weighted (IVW) approach supplemented with the MR-Egger and weighted median methods. Sensitivity analyses were used to further assess the reliability of the main MR study findings. The possibility of reverse causation was also evaluated using a reverse MR approach.ResultsThe IVW MR analytical approach revealed that IBD (p = 0.074), UC (p = 0.094), and CD (p = 0.644) had no significant impact on the incidence of bronchiectasis, with the converse also being true (p = 0.471, p = 0.700, and p = 0.099, respectively).ConclusionThis MR analysis demonstrated that the higher occurrence of bronchiectasis in patients with IBD is not caused by genetic predisposition.
Phenotypic immune characterization of gastric and esophageal adenocarcinomas reveals profound immune suppression in esophageal tumor locations
Authors: Groen-van Schooten Tessa S. , Harrasser Micaela , Seidel Jens , Bos Emma N. , Fleitas Tania , van Mourik Monique , Pouw Roos E. , Goedegebuure Ruben S. A. , Doeve Benthe H. , Sanders Jasper , Bos Joris , van Berge Henegouwen Mark I. , Thijssen Victor L. J. L. , van Grieken Nicole C. T. , van Laarhoven Hanneke W. M. , de Gruijl Tanja D. , Derks Sarah 
Published: April 2024

BackgroundTumors in the distal esophagus (EAC), gastro-esophageal junction including cardia (GEJAC), and stomach (GAC) develop in close proximity and show strong similarities on a molecular and cellular level. However, recent clinical data showed that the effectiveness of chemo-immunotherapy is limited to a subset of GEAC patients and that EACs and GEJACs generally benefit less from checkpoint inhibition compared to GACs. As the composition of the tumor immune microenvironment drives response to (immuno)therapy we here performed a detailed immune analysis of a large series of GEACs to facilitate the development of a more individualized immunomodulatory strategy.MethodsExtensive immunophenotyping was performed by 14-color flow cytometry in a prospective study to detail the immune composition of untreated gastro-esophageal cancers (n=104) using fresh tumor biopsies of 35 EACs, 38 GEJACs and 31 GACs. The immune cell composition of GEACs was characterized and correlated with clinicopathologic features such as tumor location, MSI and HER2 status. The spatial immune architecture of a subset of tumors (n=30) was evaluated using multiplex immunohistochemistry (mIHC) which allowed us to determine the tumor infiltration status of CD3+, CD8+, FoxP3+, CD163+ and Ki67+ cells.ResultsImmunophenotyping revealed that the tumor immune microenvironment of GEACs is heterogeneous and that immune suppressive cell populations such as monocytic myeloid-derived suppressor cells (mMDSC) are more abundant in EACs compared to GACs (p&lt;0.001). In contrast, GACs indicated a proinflammatory microenvironment with elevated frequencies of proliferating (Ki67+) CD4 Th cells (p&lt;0.001), Ki67+ CD8 T cells (p=0.002), and CD8 effector memory-T cells (p=0.024). Differences between EACs and GACs were confirmed by mIHC analyses showing lower densities of tumor- and stroma-infiltrating Ki67+ CD8 T cells in EAC compared to GAC (both p=0.021).DiscussionsThis comprehensive immune phenotype study of a large series of untreated GEACs, identified that tumors with an esophageal tumor location have more immune suppressive features compared to tumors in the gastro-esophageal junction or stomach which might explain the location-specific responses to checkpoint inhibitors in this disease. These findings provide an important rationale for stratification according to tumor location in clinical studies and the development of location-dependent immunomodulatory treatment approaches.
Prolidase could be considered a sign of inflammation associated with cigarette smoking
Authors: Yıldırım Berna Botan , Kulaksızoglu Sevsen 
Published: April 2024

ObjectivesSmoking causes inflammation, thickening, and narrowing of the airways. This inflammatory process is a reaction to free radicals and oxidants. Smoking affects collagen metabolism and tissue remodeling. Prolidase enzyme hydrolyzes iminodipeptides with hydroxyproline and C terminal proline. It plays a crucial role in the metabolism of collagen and the remodeling of the matrix. The present study aims to reveal the association of prolidase with inflammation caused by smoking and to compare serum prolidase levels with oxidative-antioxidative status in healthy individuals.MethodsA total of 76 participants (38 smokers and 38 nonsmokers) were involved in the present study. Serum cotinine levels were measured to show the exposure to nicotine in tobacco smoke by using the competitive inhibition enzyme immunoassay method. Serum prolidase, total oxidant status (TOS), and total antioxidant status (TAS) were determined by the enzyme-linked immunosorbent (ELISA) method, respectively. The correlation between smoking, serum prolidase levels, TOS, and TAS was investigated.ResultsTAS and serum prolidase levels of smokers were considerably lower than those in non-smokers (p &lt; 0.001, p = 0.012 respectively). However, no differences were observed in TOS between the two groups. There was no statistically significant correlation between serum prolidase levels, TAS, and TOS. Moreover, no relationship was observed between respiratory function parameters and serum prolidase levels.ConclusionTo the best of our knowledge, the present study is the first study to demonstrate the role of prolidase in smoking-related inflammation. The results achieved in the present study suggest that smoking creates an imbalance in the oxidant-antioxidant activity. Smoking decreases prolidase levels, leading to decreased collagen turnover. Chronic pulmonary disease might be related to this decrease in collagen turnover.
Influence of ethnic origin on the clinical characteristics and intestinal flora of irritable bowel syndrome: a prospective study between Han and Tibetan patients
Authors: Ma Xiao , Huan Hui , Liu Chao , Hu Hong , Ren Tao 
Published: April 2024

BackgroundFew studies have focused on the clinical characteristics and intestinal flora of Tibetan patients with irritable bowel syndrome (IBS). The study aimed to compare the difference of between Tibetan and Han patients with IBS.MethodsPatients who met inclusion and exclusion criteria were divided into the Tibet and Han groups. A simplified Gastrointestinal Symptom Rating Scale (GSRS)-based questionnaire was used to assess the IBS severity. Fecal samples from all subjects were collected for the analysis of gut microbiota using 16sRNA Illumina sequencing.ResultsNo significant difference was found in the total symptom scores between two groups. However, Tibetans with IBS are more prone to bloating than Hans (17.41% vs 9.09%, p &lt; 0.001). A profit shift in the gut microbiota was shown between the two groups. The ratio of Firmicutes/Bacteroidetes was significantly lower in the Tibet group than in the Han group (2.954 ± 0.78 vs 8.23 ± 2.04, p = 0.004). In the Tibet group, the level of the genus Blautia decreased significantly compared to the Han group, and there was a significant negative correlation between the level of Blautia and the bloating scores (Pearson r = −0.33, p = 0.025).ConclusionThe characteristics of Tibetan patients differ from those of Han patients with IBS, not only in terms of the clinical symptoms, but also in the characteristics of intestinal flora. Tibetans with IBS are more prone to bloating, which might be due to the different gut microbiota. The genus Blautia may play a role in this mechanism.
Global, regional, and national burden and trends analysis of gallbladder and biliary tract cancer from 1990 to 2019 and predictions to 2030: a systematic analysis for the Global Burden of Disease Study 2019
Authors: Su Jiao , Liang Yuanhao , He Xiaofeng 
Published: April 2024

ObjectivesOur aim was to explore the disease burden caused by gallbladder and biliary tract cancer globally, regionally, and nationally, by age and sex.MethodsThe absolute number of cases and age-standardized rates (ASR) of incidence, prevalence, mortality, and disability-adjusted life years (DALYs) due to gallbladder and biliary tract cancer were extracted from the Global Burden of Disease (GBD) Study 2019. We estimated the trends in disease burden by calculating the percentage change in the absolute number of cases and the estimated annual percentage change (EAPC) in ASR, by social development index (SDI), region, nation, sex, and age.ResultsFrom 1990 to 2019, the number of incident cases, prevalent cases, deaths, and DALYs worldwide significantly increased by 1.85-fold, 1.92-fold, 1.82-fold, and 1.68-fold, respectively. However, the age-standardized rates of incidence, prevalence, mortality, and DALYs tend to decrease globally over time. Nevertheless, heterogeneous disease burden patterns exist between geographic regions due to different geographical risk factors, distinct epidemiologically predominant gallbladder and biliary tract cancer subtypes, and potential genetic predispositions or ethnicity. Additionally, socioeconomic status mediates the regional variation in disease burden, with increasing SDI or HDI scores associated with downward trends in the age-standardized rates of incidence, prevalence, mortality, and DALYs. Older individuals and females are at higher risk of gallbladder and biliary tract cancer, but the increasing burden of early-onset gallbladder and biliary tract cancer is a cause for concern, especially for those living in lower SDI areas and males. High BMI is the primary risk factors underlying gallbladder and biliary tract cancer, accounted for 15.2% of deaths and 15.7% DALYs globally in 2019.ConclusionOur study comprehensively elucidated the distribution and dynamic trends of gallbladder and biliary tract cancer burden over the past three decades, from multiple dimensions. These findings emphasize the importance of promoting a healthy lifestyle as a population-level cancer prevention strategy and tailoring cancer control actions based on localized risk factors and the epidemic profiles of gallbladder and biliary tract cancer by anatomical subtype.