bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developmental progression of lymphatic valve morphology and function
Authors: Davis Michael J. , Zawieja Scott D. , Yang Ying 
Published: February 2024

Introduction: The bileaflet valves found in collecting lymphatic vessels and some veins are essential for maintaining a unidirectional flow, which is important for lymphatic and venous function. Under an adverse pressure gradient, the two leaflets tightly overlap to prevent backflow. Valves are proposed to share four main stages of development, based on images obtained from randomly oriented valves in fixed mouse embryos, with the best structural views obtained from larger venous valves. It is not known at what stage lymphatic valves (LVs) become functional (e.g., able to oppose backflow), although a requirement for stage 4 is presumed.Methods: To gain an insight into this sequence of events for LVs, we used Prox1CreERT2:Foxo1fl/fl mice and Foxc2CreERT2:Foxo1fl/fl mouse models, in which deletion of the valve repressor factor Foxo1 promotes the development of new LVs in adult lymphatic vessels. Both strains also contained a Prox1eGFP reporter to image the lymphatic endothelium. Mesenteric collecting lymphatic vessels were dissected, cannulated, and pressurized for ex vivo tests of valve function. LVs at various stages (1–4 and intermediate) were identified in multi-valve segments, which were subsequently shortened to perform the backleak test on single valves. The GFP signal was then imaged at high magnification using a confocal microscope. Z-stack reconstructions enabled 1:1 comparisons of LV morphology with a quantitative measurement of back leak.Results: As expected, LVs of stages 1–3 were completely leaky in response to outflow pressure elevation. Stage 4 valves were generally not leaky, but valve integrity depended on the Cre line used to induce new valve formation. A high percentage of valves at leaflet an intermediate stage (3.5), in which there was an insertion of a second commissure, but without proper luminal alignment, effectively resisted back leak when the outflow pressure was increased.Discussion: Our findings represent the first 3D images of developing lymphatic valves and indicate that valves become competent between stages 3 and 4 of development.
High platelet adrenergic activity and concomitant activation of the pituitary/medullar axis as alarming laboratory parameters in ACS survivors—the STRESS-AMI study
Authors: Gulyás Zalán , Horváth Zsófia , Hajtman László , Kovács Andrea , Kohut László , Kósa István , Tóth-Zsámboki Emese , Kiss Róbert Gábor 
Published: February 2024

IntroductionKinetics of stress-related biological parameters were determined in acute coronary syndrome (ACS) patients undergoing complex cardiovascular rehabilitation.MethodsWe determined platelet functionality in the absence/presence of a selective alpha-2 adrenergic receptor inhibitor, atipemazole parallel with salivary cortisol levels at enrolment, and at 3- and 12-months follow-up in 75 ACS patients with percutaneous coronary intervention.ResultsPharmacological/non-pharmacological secondary prevention methods have been efficiently applied. Baseline aggregometry indicated platelet hyperactivity, decreasing gradually and being significantly reduced late, at 12 months (p &lt; 0.05). Cortisol levels followed similar kinetics (p &lt; 0.05). Baseline epinephrine-induced aggregations (EIA) significantly correlated with most of the other platelet agonists, even at subsequent time-points. Patients with upper-quartile EIA at enrolment (EIA-UQ) had significantly higher ADP- and collagen-induced aggregations at enrolment, at 3- and 12-months follow-up as well, indicating that high adrenergic response in the acute phase is accompanied by general platelet hyperactivity and predicts sustained platelet activation. In the EIA-UQ group higher cardiac biomarker release, elevated C-reactive protein and cortisol levels, and lower baseline left ventricular ejection fraction were detected.Atipemazole significantly reduced platelet aggregation induced by several platelet agonists, being most potent and comparable to full in vitro P2Y12 inhibition on collagen-induced aggregations (p &lt; 0.05), indicating that catecholamines might serve as promt/long-term modulators of platelet function.DiscussionDespite effective CCR programme and dual antiplatelet therapy, prolonged activation of sympathetic neuroendocrine system and general platelet hyperactivity can be detected up to one year in ACS patients with high adrenergic platelet activity. Moreover, initial high adrenergic activity is accompanied by clinical parameters associated to increased cardiovascular risk, therefore early identification of these patients might support complex optimal long-term therapy.
Effectiveness of educational interventions in minimizing reactance in traffic accident prevention
Authors: von Beesten Silke , Bresges André , Lubert Daniela 
Published: February 2024

IntroductionClassical mechanics concepts are vital for understanding traffic safety, encompassing speed, acceleration, stopping distance, impact speed, deformation, kinetic energy, and their effects on vehicle occupants. Statistical physics principles are also employed to study multiple vehicles as a many-particle system. This study examines the effectiveness of using a damaged car and structured instruction in road safety initiatives.MethodsParticipants engaged with a damaged car and discussed deformation caused by excessive speed. They participated in role simulations, envisioning and solving risky traffic scenarios, while considering the potential boomerang effect resulting from excessive fear appeals within the campaign.ResultsCombining emotional appeals with solution-focused, action-oriented, and self-esteem-enhancing interventions is essential to mitigate the boomerang effect and encourage safety-compliant behavior. Educational institutions must implement tailored follow-ups to emotionally charged prevention campaigns. Using Design-Based Research, we developed effective methods for knowledge acquisition and transfer, drawing from cognitive behavioral therapy and established traffic safety programs.DiscussionThis publication explores non-standardized social training within focus groups, focusing on negative emotional states following an emotionalizing campaign similar to “Crash Kurs NRW,” targeting upper-level courses in North Rhine-Westphalian schools. Methods from cognitive behavioral therapy and social learning initiated, observed, and documented changes in participants’ norms, values, and attitudes, discussed herein. Additionally, we investigated whether the presence of police officers in prevention campaigns influences reactive behavior. Comparing pre- and post-surveys confirmed reactance after emotionalizing campaigns, and our structured post-survey effectively influenced stage-event-induced behavior. Surprisingly, police officers’ presence did not significantly impact reactive behavior. Furthermore, our follow-up tool extends its applicability to similar emotionalizing prevention campaigns, broadening its potential reach. Our future research will delve into students’ physics literacy during traffic space analysis of accident hotspots, advancing traffic safety initiatives.
Risk factors, prognostic factors, and nomograms for distant metastases in patients with gastroenteropancreatic neuroendocrine tumors: a population-based study
Authors: Li Xinwei , Fan Yongfei , Tong Jichun , Lou Ming 
Published: February 2024

BackgroundPatients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) have a poor prognosis for distant metastasis. Currently, there are no studies on predictive models for the risk of distant metastasis in GEP-NETs.MethodsIn this study, risk factors associated with metastasis in patients with GEP-NETs in the Surveillance, Epidemiology, and End Results (SEER) database were analyzed by univariate and multivariate logistic regression, and a nomogram model for metastasis risk prediction was constructed. Prognostic factors associated with distant metastasis in patients with GEP-NETs were analyzed by univariate and multivariate Cox, and a nomogram model for prognostic prediction was constructed. Finally, the performance of the nomogram model predictions is validated by internal validation set and external validation set.ResultsA total of 9145 patients with GEP-NETs were enrolled in this study. Univariate and multivariate logistic analysis demonstrated that T stage, N stage, tumor size, primary site, and histologic types independent risk factors associated with distant metastasis in GEP-NETs patients (p value &lt; 0.05). Univariate and multivariate Cox analyses demonstrated that age, histologic type, tumor size, N stage, and primary site surgery were independent factors associated with the prognosis of patients with GEP-NETs (p value &lt; 0.05). The nomogram model constructed based on metastasis risk factors and prognostic factors can predict the occurrence of metastasis and patient prognosis of GEP-NETs very effectively in the internal training and validation sets as well as in the external validation set.ConclusionIn conclusion, we constructed a new distant metastasis risk nomogram model and a new prognostic nomogram model for GEP-NETs patients, which provides a decision-making reference for individualized treatment of clinical patients.
Associations between the platelet/high-density lipoprotein cholesterol ratio and likelihood of nephrolithiasis: a cross-sectional analysis in United States adults
Authors: Ni Junjie , Lv Lin , Wu Pu , Xu Chaoyang 
Published: February 2024

AimsThe primary objective of this study was to investigate the relationship between the platelet/high-density lipoprotein cholesterol ratio (PHR) and the prevalence of nephrolithiasis within the adult population of the United States.MethodsThe data used in this study were obtained from the National Health and Nutrition Examination Survey (NHANES) conducted between 2007 and 2018. The analysis included a non-pregnant population aged 20 years or older, providing proper PHR index and nephrolithiasis data. The research utilized subgroup analyses and weighted univariate and multivariable logistic regression to evaluate the independent association between the PHR and the susceptibility to nephrolithiasis.ResultsThe study comprised 30,899 participants with an average PHR value of 19.30 ± 0.11. The overall prevalence rate of nephrolithiasis was estimated at 9.98% with an increase in the higher PHR tertiles (T1, 8.49%; T2, 10.11%; T3, 11.38%, P &lt; 0.0001). An elevated PHR level was closely linked with a higher susceptibility to nephrolithiasis. Compared with patients in T1, and after adjusting for potential confounders in model 2, the corresponding odds ratio for nephrolithiasis in T3 was 1.48 (95% CI: 1.06 to 2.08), with a P-value = 0.02. The results of the interaction tests revealed a significant impact of chronic kidney disease on the relationship between PHR and nephrolithiasis. Furthermore, the restricted cubic spline analyses exhibited a positive, non-linear correlation between PHR and the risk of nephrolithiasis.ConclusionA convenient biomarker, the PHR, was independently associated with nephrolithiasis and could be a novel biomarker in predicting occurrence in clinical decision.
Impact of bronchoalveolar lavage from influenza A virus diseased pigs on neutrophil functions and growth of co-infecting pathogenic bacteria
Authors: Lassnig Simon , Hennig-Pauka Isabel , Bonilla Marta C. , Mörgelin Matthias , Imker Rabea , von Köckritz-Blickwede Maren , de Buhr Nicole 
Published: February 2024

IntroductionInfluenza A viruses (IAVs) infect the respiratory tract of mainly humans, poultry, and pigs. Co-infections with pathogenic lung bacteria are a common event and contribute to the severity of disease progression. Neutrophils are a major cell type of the innate immune system and are rapidly recruited to the site of infection. They have several effector functions to fight invading pathogens such as the secretion of reactive oxygen species (ROS) or the release of neutrophil extracellular traps (NETs). NETs are known to promote the growth of Pasteurellaceae bacteria, especially if degraded by nucleases.MethodsIn this study, bronchoalveolar lavage fluid (BALF) from 45 field-infected pigs was analyzed for 1) NET markers, 2) influence on growth of lung bacteria, and 3) impact on neutrophil functions. BALF samples from 21 IAV-positive pigs and 24 lung diseased but IAV-negative pigs were compared.ResultsHere, we show that neutrophils in the lungs of IAV-positive pigs release vesicular NETs. Several NET markers were increased in the BALF of IAV-positive pigs compared with the BALF from IAV-negative pigs. The amount of NET markers positively correlated with the viral load of the IAV infection. Interestingly, the BALF of IAV-positive pigs enhanced the growth of bacteria belonging to the family of Pasteurellaceae as potential coinfecting bacteria. These effects were weaker with the BALF derived from IAV-negative pigs with other lung infections. The intensity of oxidative burst in neutrophils was significantly decreased by BALF from IAVpositive pigs, indicating impaired antimicrobial activity of neutrophils. Finally, the lung milieu reflected by IAV-positive BALF does not enable neutrophils to kill Actinobacillus pleuropneumoniae but rather enhances its growth.DiscussionIn summary, our data show that an IAV infection is affecting neutrophil functions, in particular the release of NETs and ROS. Furthermore, IAV infection seems to provide growth-enhancing factors for especially coinfecting Pasteurellaceae and reduces the killing efficiency of neutrophils.
Systemic immune-inflammation Index is associated with chronic kidney disease in the U.S. population: insights from NHANES 2007–2018
Authors: Liu Xiaoxin , Li Xinyu , Chen Yulin , Liu Xiaoyu , Liu Yanyan , Wei Haotian , Li Ningxu 
Published: February 2024

ObjectivesThe systemic immune-inflammation index (SII), a novel and systematic inflammatory biomarker that is associated with chronic kidney disease (CKD), has not received much attention. This study aimed to investigate the relationship between SII and CKD in the United States (U.S.) population.MethodsOur study ultimately included a nationally representative sample of 10,787 adults who participated in the 2007-2018 National Health and Nutrition Examination Survey. Weighted multivariate logistic regression was used to assess the correlation between SII and CKD, and a restricted cubic spline (RCS) model was subsequently used to explore the non-linear relationship between SII and CKD. Subgroup analyses were performed to further the effects of other covariates on the relationship between SII and CKD.ResultsFollowing confounder adjustment, a higher SII was related to the incidence of CKD (OR =1.36; 95% CI, 1.07–1.73; p =0.01), as validated by multivariable logistic regression. The RCS curve revealed a non-linear positive correlation between SII/1000 and CKD incidence (p for non-linear =0.0206). Additionally, subgroup analysis confirmed a stronger correlation for male participants (OR =2.628; 95% CI, 1.829-3.776) than for female participants (OR =1.733; 95% CI, 1.379-2.178) (p for interaction =0.046).ConclusionsSII is positively associated with the incidence of CKD among U.S. adults, especially in males. However, further studies are needed to confirm our findings and explore the causal factors that can contribute to the prevention and treatment of CKD.
Phenotypic and genotypic characterization of Campylobacter coli isolates from the Vietnamese poultry production network; a pilot study
Authors: Lehri Burhan , Navoly Georgina , Corser Abigail , Nasher Fauzy , Willcocks Sam , Pham Thi Ngoc , Wren Brendan W. , Luu Quynh Huong , Stabler Richard A. 
Published: February 2024

IntroductionChanging farming practices and the associated increase in the use of antibiotics are amongst the main drivers shaping the global increase of Campylobacter infections. The effects farming practices have on Campylobacter species, need to be studied at the global scale, particularly in emerging middle-income countries, where the demand for low-cost poultry meat is rising. While Campylobacter jejuni causes the majority of poultry associated diarrhoea, Campylobacter coli causes a significant amount of disease but are relatively understudied. In this study we characterised seven C. coli strains isolated from chicken faeces and chicken meat in Thai Nguyen province, Vietnam.MethodsWhole Genome Sequencing and phenotypic assays (growth, motility, antimicrobial resistance testing, virulence assay) were performed to reveal the genetic relatedness and pathophysiological characteristics of the isolates. ResultsAll isolates were resistant to ciprofloxacin and nalidixic acid but susceptible to phenicols. Three were resistant to macrolides azithromycin and erythromycin. Six isolates were classified as multi-drug resistant. All isolates had similar growth rates in laboratory culture media, while five were hyper-motile. Lethality towards a tractable host-model system, larvae of the greater wax moth Galleria mellonella, often used to determine Campylobacter virulence, was demonstrated for the first time for C. coli. DiscussionMultilocus sequence typing data identified five ST’s all within the C. coli ST-828 clonal complex and were previously reported in North American (ST-829), European (ST-1586), and Asia (ST-5511) from patients suffering from gastroenteritis, emphasising the global spread of these strains. This work highlights the importance of further research into this understudied global threat.
An investigation for the efficacy of teaching model of combining virtual simulation and real experiment for clinical microbiology examination
Authors: Meng Ling , Liu Xia , Ni Jing , Shen Pei , Jiao Fengping 
Published: February 2024

BackgroundAs a convenient teaching tool, virtual simulation experiment technology had been widely utilized in the field of medical education. However, virtual learning could not fully replace the benefits of in-person instruction. Therefore, finding ways to integrate both methods was crucial for achieving optimal educational outcomes. The objective of this study was to compare the effectiveness of the self-built virtual simulation and design experiment combining teaching mode and the traditional experimental teaching mode in the clinical microbiology examination experiment teaching.MethodsThis study was conducted at Shandong First Medical University in China. The experimental group consisted of 100 third-year students from the grade 2020 majoring in medical examination technology, who underwent an innovative teaching model combining virtual and real experiments. The control group comprised of 100 third-year students from the grade 2019 in the same major, who received traditional experimental teaching model. In this study, we referred to grade 2020 as cohort 2020 and grade 2019 cohort 2019. The performance of both groups was assessed via experimental and theoretical testing. Meanwhile, survey questionnaires were administered to evaluate the efficacy of the innovative experimental teaching model and students’ level of satisfaction with it. Cohort 2020 conducted a survey for modules 1 to 4, while cohort 2019 only conducted a survey for module 4, as detailed in the Appendix.ResultsThe majority of students in the experimental group expressed satisfaction with the teaching model that combined virtual and real experiments, as evidenced by their superior performance on both experimental operational skills (87.54 ± 8.93 vs. 82.39 ± 10.55) and theoretical knowledge tests (83.65 ± 9.02 vs. 80.18 ± 8.24) compared to those in the control group.ConclusionThe combination of virtual simulation experiment and design experiment in the microbiological examination of clinical specimens represented an effective pedagogical approach. The instructional approach had the potential to incite a passion for learning, enhance proficiency in standardized experimental techniques, foster the ability to integrate theory with practice, and cultivate clinical reasoning skills.
Gene expression in metastatic breast cancer—patterns in primary tumors and metastatic tissue with prognostic potential
Authors: Tutzauer Julia , Larsson Anna-Maria , Aaltonen Kristina , Bergenfelz Caroline , Bendahl Pär-Ola , Rydén Lisa 
Published: February 2024

Background: Metastatic breast cancer (MBC) is the main cause of breast cancer-related death. The outcome of MBC varies, and there is a lack of biomarkers to aid in prognostication. The primary aim of this study was to evaluate the prognostic value of gene expression (GEX) signatures in the primary tumor (PT) and distant metastasis (DM) for progression-free survival (PFS) and overall survival (OS). The secondary aim was to describe GEX changes through MBC evolution and to identify MBC subtypes.Methods: RNA was extracted from the PT, lymph node metastasis (LNM), and DM from MBC patients in a prospective observational study (n = 142; CTC-MBC NCT01322893) and was subjected to GEX analysis retrospectively using the NanoString Breast Cancer 360™ panel. 31 continuous GEX variables in DMs and PTs were analyzed for PFS and OS by Cox regression analysis and Kaplan-Meier estimates. Multivariable Cox regressions were adjusted for number of DM sites and CTCs, visceral metastasis, ECOG status, age at MBC diagnosis and, in additional analyses, PAM50 subtype. Differential GEX analyses and Euclidean distances were used to describe subgroup differences and visualize within-patient heterogeneity.Results: Compared to DM GEX, GEX of the PT was at least equally useful for predicting MBC outcome. The strongest marker for a favorable PFS, both when expressed in the PT and the DM was AR, even after adjustment for prognostic markers including PAM50. GEX signatures related to hormone responsiveness, including ESR1, FOXA1, PGR, and AR were favorable prognostic markers, and the p53 signature was unfavorable for PFS when expressed in PT or DM. The previously published PAM50MET signature was prognostic for both PFS and OS. We established five distinct DM GEX profiles where two associated with liver and bone metastases, respectively. Finally, we identified four DM GEX profiles able to identify MBCs with poor OS in this cohort.Conclusion: GEX of both DM and PT are useful in MBC prognostication. GEX of AR adds prognostic information for MBC. Our descriptive analyses illuminate the biological differences between MBCs in relation to outcome and metastatic site.