bluuebunny/crossref_metadata_2025_split huggingface dataset:
Baseline fibroblast growth factor 23 is associated with long-term mortality in ST-elevation myocardial infarction—results from the augsburg myocardial infarction registry
Authors: Schmitz Timo , Wein Bastian , Heier Margit , Peters Annette , Meisinger Christa , Linseisen Jakob 
Published: August 2023

BackgroundThe aim of this study was to investigate the association between inflammatory plasma protein concentrations and long-term mortality in patients with ST-elevation myocardial infarction (STEMI).MethodsFor 343 STEMI patients recorded between 2009 and 2013 by the population-based Myocardial Infarction Registry Augsburg, 92 inflammatory plasma proteins were measured at the index event using the OLINK inflammation panel. In multivariable-adjusted Cox regression models, the association between each plasma protein and all-cause long-term mortality was investigated. Median follow-up time was 7.6 (IQR: 2.4) years. For plasma protein that showed a strong association with long-term mortality, a 5-year survival ROC analysis was performed.ResultsOne plasma protein, namely Fibroblast Growth Factor 23 (FGF-23), was particularly well associated with long-term mortality in the multivariable-adjusted Cox model with an FDR-adjusted p-value of &lt;0.001 and a Hazard Ratio (HR) of 1.57 [95% CI: 1.29–1.91]. In the 5-years ROC analysis, an AUC of 0.6903 [95% CI: 0.594–0.781] was estimated for FGF-23. All other plasma protein didńt show strong associations, each marker with FDR-adjusted p-values &gt;0.05 in the multivariable-adjusted Cox models.ConclusionsFGF-23 is independently associated with long-term mortality after STEMI and might play an important role in the response to myocardial injury. The results suggest FGF-23 to be a useful marker in the long-term treatment of STEMI patients and a potential target for drug development.
Extracellular Vesicles-mediated recombinant IL-10 protects against ascending infection-associated preterm birth by reducing fetal inflammatory response
Authors: Kammala Ananth Kumar , Mosebarger Angela , Radnaa Enkhtuya , Rowlinson Emma , Vora Natasha , Fortunato Stephen J. , Sharma Surendra , Safarzadeh Melody , Menon Ramkumar 
Published: August 2023

BackgroundFetal inflammatory response mediated by the influx of immune cells and activation of pro-inflammatory transcription factor NF-κB in feto-maternal uterine tissues is the major determinant of infection-associated preterm birth (PTB, live births &lt; 37 weeks of gestation).ObjectiveTo reduce the incidence of PTB by minimizing inflammation, extracellular vesicles (EVs) were electroporetically engineered to contain anti-inflammatory cytokine interleukin (IL)-10 (eIL-10), and their efficacy was tested in an ascending model of infection (vaginal administration of E. coli) induced PTB in mouse models.Study designEVs (size: 30-170 nm) derived from HEK293T cells were electroporated with recombinant IL-10 at 500 volts and 125 Ω, and 6 pulses to generate eIL-10. eIL-10 structural characters (electron microscopy, nanoparticle tracking analysis, ExoView [size and cargo content] and functional properties (co-treatment of macrophage cells with LPS and eIL-10) were assessed. To test efficacy, CD1 mice were vaginally inoculated with E. coli (1010CFU) and subsequently treated with either PBS, eIL-10 (500ng) or Gentamicin (10mg/kg) or a combination of eIL-10+gentamicin. Fetal inflammatory response in maternal and fetal tissues after the infection or treatment were conducted by suspension Cytometer Time of Flight (CyTOF) using a transgenic mouse model that express red fluorescent TdTomato (mT+) in fetal cells.ResultsEngineered EVs were structurally and functionally stable and showed reduced proinflammatory cytokine production from LPS challenged macrophage cells in vitro. Maternal administration of eIL-10 (10 µg/kg body weight) crossed feto-maternal barriers to delay E. coli-induced PTB to deliver live pups at term. Delay in PTB was associated with reduced feto-maternal uterine inflammation (immune cell infiltration and histologic chorioamnionitis, NF-κB activation, and proinflammatory cytokine production).ConclusionseIL-10 administration was safe, stable, specific, delayed PTB by over 72 hrs and delivered live pups. The delivery of drugs using EVs overcomes the limitations of in-utero fetal interventions. Protecting IL-10 in EVs eliminates the need for the amniotic administration of recombinant IL-10 for its efficacy.
Saccharomyces boulardii CNCM I-745 supplementation during and after antibiotic treatment positively influences the bacterial gut microbiota
Authors: Spatz Madeleine , Wang Yazhou , Lapiere Alexia , Da Costa Gregory , Michaudel Chloé , Danne Camille , Michel Marie-Laure , Langella Philippe , Sokol Harry , Richard Mathias L. 
Published: August 2023

IntroductionAntibiotic effects on gut bacteria have been widely studied, but very little is known about the consequences of such treatments on the mycobiota, the fungal part of the microbiota and how the length of administration influences both microbiota. Here, we examined the effect of antibiotics (ATB) on the composition of bacterial and fungal microbiota and how the administration of Saccharomyces boulardii CNCM I-745 influences both microbiota.MethodsIn order to get closer to the human microbiota, the mice used in this study were subjected to fecal microbiota transfer (FMT) using human feces and subsequently called human microbiotaassociated (HMA) mice. These mice were then treated with amoxicillinclavulanate antibiotics and supplemented with S. boulardii during and after ATB treatment to understand the effect of the yeast probiotic on both bacterial and fungal microbiota. Bacterial and fungal microbiota analyses were done using 16S and ITS2 rRNA amplicon-based sequencing.ResultsWe showed that the administration of S. boulardii during ATB treatment had very limited effect on the fungal populations on the long term, once the yeast probiotic has been cleared from the gut. Concerning bacterial microbiota, S. boulardii administration allowed a better recovery of bacterial populations after the end of the ATB treatment period. Additionally, 16S and ITS2 rRNA sequence analysis revealed that 7 additional days of S. boulardii administration (17 days in total) enhanced the return of the initial bacterial equilibrium.DiscussionIn this study, we provide a comprehensive analysis of how probiotic yeast administration can influence the fungal and bacterial microbiota in a model of broad-spectrum antibiotherapy.
Functional analysis of CTLA4 promoter variant and its possible implication in colorectal cancer immunotherapy
Authors: Angulo-Aguado Mariana , Orjuela-Amarillo Sarah , Mora-Jácome Julián Francisco , Córdoba Lea Paloma , Gallego-Ortiz Antonio , Gaviria-Sabogal Cristian Camilo , Contreras Nora , Figueroa Carlos , Ortega-Recalde Oscar , Morel Adrien , Fonseca-Mendoza Dora Janeth 
Published: August 2023

BackgroundColorectal cancer (CRC) is a prevalent cancer, ranking as the third most common. Recent advances in our understanding of the molecular causes of this disease have highlighted the crucial role of tumor immune evasion in its initiation and progression. CTLA4, a receptor that acts as a negative regulator of T cell responses, plays a pivotal role in this process, and genetic variations in CTLA4 have been linked to CRC susceptibility, prognosis, and response to therapy.MethodsWe conducted a case-control study involving 98 CRC patients and 424 controls. We genotyped the CTLA4 c.-319C &gt; T variant (rs5742909) and performed an association analysis by comparing allele frequencies between the patients and controls. To assess the potential functional impact of this variant, we first performed an In Silico analysis of transcription factor binding sites using Genomatix. Finally, to validate our findings, we conducted a luciferase reporter gene assay using different cell lines and an electrophoretic mobility shift assay (EMSA).ResultsThe case-control association analysis revealed a significant association between CTLA4 c.-319C &gt; T and CRC susceptibility (p = 0.023; OR 1.89; 95% CI = 1.11–3.23). Genomatix analysis identified LEF1 and TCF7 transcription factors as specific binders to CTLA4 c.-319C. The reporter gene assay demonstrated notable differences in luciferase activity between the c.-319 C and T alleles in COS-7, HCT116, and Jurkat cell lines. EMSA analysis showed differences in TCF7 interaction with the CTLA4 C and T alleles.ConclusionCTLA4 c.-319C &gt; T is associated with CRC susceptibility. Based on our functional validation results, we proposed that CTLA4 c.-319C &gt; T alters gene expression at the transcriptional level, triggering a stronger negative regulation of T-cells and immune tumoral evasion.
Four-dimensional computed tomography detects dynamic three-dimensional pathologies of the wrist in patients with calcium pyrophosphate deposition disease
Authors: Ulas Sevtap Tugce , Pochandke Louise , Ohrndorf Sarah , Diekhoff Torsten , Ziegeler Katharina 
Published: August 2023

ObjectivesCrystal deposits in ligaments of the wrist are typical findings in patients with calcium pyrophosphate deposition (CPPD) disease. CPPD crystals trigger inflammation and ultimately result in ligament tears with scapholunate (SL) advanced collapse (SLAC). This study aimed to investigate carpal instabilities in patients with CPPD using four-dimensional computed tomography (4D-CT) of the wrist.MethodsThis IRB-approved prospective feasibility study investigated patients with CPPD of the hand. All patients underwent a static 3D-CT and two dynamic 4D-CT in ulnar- and radial abduction and in supination and pronation movements to analyze instabilities of the SL region and of the distal radioulnar joint (DRUJ). Two independent readers scored the images for the presence of SL ligament and triangular fibrocartilage complex (TFCC) calcifications. Furthermore, the readers assessed the dynamic images for SL and DRUJ instabilities. Descriptive analyses were performed. Inter-rater reliability was assessed using Cohen’s kappa (κ).ResultsNine patients were included. SL ligament calcifications and instabilities were found in all patients. Of these, dynamic SL instability was detected in 77.8% of the patients, while 22.2% had a SLAC wrist. TFCC calcifications were found in 87.5% of the patients. Four patients had DRUJ instability (50%). No patient showed DRUJ instability without the presence of TFCC calcifications. Agreement between readers for calcifications was excellent (κ = 1) and almost perfect (κ = 0.89) for instabilities.ConclusionThis study provides the first evidence of relevant dynamic carpal instability in CPPD patients using advanced imaging techniques with 4D-CT, offering unique insights into wrist biomechanics.
Rare phylotypes in stone, stool, and urine microbiomes are associated with urinary stone disease
Authors: Suryavanshi Mangesh , Agudelo Jose , Miller Aaron 
Published: August 2023

Introduction: In complex microbial communities, the importance of microbial species at very low abundance levels and their prevalence for overall community structure and function is increasingly being recognized. Clinical microbiome studies on urinary stone disease (USD) have indicated that both the gut and urinary tract microbiota are associated with the onset of the disease and that kidney stones them-selves harbor a complex, yet consistent and viable, microbiome. However, how rare phylotypes contribute to this association remains unclear. Delineating the contribution of rare and common phylotypes to urinary stone disease is important for the development of bacteriotherapies to promote urologic health.Methods: The objectives of the current report were to conduct a metaanalysis of 16S rRNA datasets derived from the kidney stone, stool, and urine samples of participants with or without urinary stone disease. To delineate the impact of rare and common phylotypes, metaanalyses were conducted by first separating rare and common taxa determined by both the frequency and abundance of amplicon sequence variants.Results: Consistent with previous analyses, we found that gut, upper urinary, and lower urinary tract microbiomes were all unique. Rare phylotypes comprised the majority of species observed in all sample types, with kidney stones exhibiting the greatest bias toward rarity, followed by urine and stool. Both rare and common fractions contributed significantly to the differences observed between sample types and health disparity. Furthermore, the rare and common fractions were taxonomically unique across all sample types. A total of 222 and 320 unique rare phylotypes from urine and stool samples were found to be significantly associated with USD. A co-occurrence correlation analysis revealed that rare phylotypes are most important for microbiome structure in stones, followed by urine and stool.Discussion: Collectively, the results indicate that rare phylotypes may be important for the pathophysiology of USD, particularly in the kidney stone matrix, which is inherently a very low microbial biomass niche that can have implications for the diagnosis and treatment of kidney stones. Further studies are needed to investigate the functional significance of rare phylotypes in kidney stone pathogenesis.
Multiple cross-frequency coupling analysis of resting-state EEG in patients with mild cognitive impairment and Alzheimer’s disease
Authors: Chen Xi , Li Yingjie , Li Renren , Yuan Xiao , Liu Meng , Zhang Wei , Li Yunxia 
Published: August 2023

IntroductionElectroencephalographic (EEG) abnormalities are seen in patients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI) with characteristic features of cognitive impairment. The most common findings of EEG features in AD and MCI patients are increased relative power of slow oscillations (delta and theta rhythms) and decreased relative power of fast oscillations (alpha, beta and gamma rhythms). However, impairments in cognitive processes in AD and MCI are not sufficiently reflected by brain oscillatory activity in a particular frequency band. MCI patients are at high risk of progressing to AD. Cross-frequency coupling (CFC), which refers to coupling between different frequency bands, is a crucial tool for comprehending changes in brain oscillations and cognitive performance. CFC features exhibit some specificity in patients with AD and MCI, but a comparison between CFC features in individuals with these disorders is still lacking. The aim of this study was to explore changes in CFC properties in MCI and AD and to explore the relationship between CFC properties and multiple types of cognitive functional performance.MethodsWe recorded resting-state EEG (rsEEG) signals in 46 MCI patients, 43 AD patients, and 43 cognitively healthy controls (HCs) and analyzed the changes in CFC as well as the relationship between CFC and scores on clinical tests of cognitive function.Results and discussionMultiple couplings between low-frequency oscillations and high-frequency oscillations were found to be significantly enhanced in AD patients compared to those of HCs and MCI, while delta-gamma as well as theta-gamma couplings in the right temporal and parietal lobes were significantly enhanced in MCI patients compared to HCs. Moreover, theta-gamma coupling in the right temporal lobe tended to be stronger in MCI patients than in HCs, and it was stronger in AD than in MCI. Multiple CFC properties were found to correlate significantly with various cognitive domains, especially the memory function domain. Overall, these findings suggest that AD and MCI patients must use more neural resources to maintain a resting brain state and that alterations in theta-gamma coupling in the temporal lobe become progressively obvious during disease progression and are likely to be a valuable indicator of MCI and AD pathology.
Therapeutic and prognostic features in myasthenia gravis patients followed in a tertiary neuromuscular diseases center in Turkey
Authors: Yaman Aylin , Kurtuluş Aydın Fatma 
Published: August 2023

IntroductionIn this study, we aim to evaluate the treatment responses and prognostic characteristics of Myasthenia Gravis (MG) patients followed in a tertiary neuromuscular diseases center in Turkey.MethodsOne hundred seventy four MG patients (between years 2011 and 2022) in Antalya, Turkey were diagnosed, and evaluated on a classification of MG was based on Myasthenia. Gravis Foundation of America (MGFA) clinical classification. Exclusion of other possible diseases in the differential diagnosis and support by beneficial response to treatment with acetylcholinesterase inhibitors were also taken into consideration.ResultsMean age of participants was 54.86 (SD = 14.856; min-max = 22–84). Ninety (51.7%) were female. MG was more common in women under the age of 65 (58%) and in men over the age of 65 (64%). Generalized MG was seen in 75.3% of the patients. Anti-AChR positivities were detected in 52.3%, Anti-MuSK positivity in 4.6%, and seronegativity in 22.4%. Thymoma was detected in nearly 9.8% and thymectomy was performed in 28.7 percent. Most of the patients (57.5%) were using corticosteroids. Azathioprine was used by 39% and mycophenolate mofetil by 10.3% of patients. Mortality was higher and disease was more severe in late-onset (&gt;50 years) MG patients (especially in the COVID-19 pandemic). Eight patients (four women, four men, mean age 75.5 years) died during follow-up. None of them died due to myasthenic worsening, two died due to malignancy and two due to infection. During the COVID pandemic, 16 patients (9.2%) had COVID infection. Four patients died due to COVID-19 infection, these four patients had serious comorbidities, and three of them were elderly (&gt;75 years).ConclusionIn conclusion, MG is more common in women between the ages of 20–40 and in men over the age of 65. The use of corticosteroids was more common under the age of 50, and the use of non-steroidal immunosuppressant agents was more common over the age of 50. Thymectomy is still an important supportive treatment approach in anti-AChR positive and seronegative generalized patients under 50 years of age. IVIG and plasmapheresis are effective treatments during acute exacerbations and bridging periods of treatments. Specific treatments are needed especially for resistant group of patients.
Effects of oral intake fruit or fruit extract on skin aging in healthy adults: a systematic review and Meta-analysis of randomized controlled trials
Authors: Li Haoying , Wang Lu , Feng Jinhong , Jiang Lijuan , Wu Jingping 
Published: August 2023

BackgroundIn recent years, oral various fruits or supplements of fruits natural extracts have been reported to have significant anti-aging effects on the skin (1, 2), However, despite many studies on this topic, there is often no clear evidence to support their efficacy and safety. In this paper, we present a comprehensive review and Meta-analysis of the evidence for the safety and efficacy of oral fruits and fruits extracts in improving skin aging.MethodsFour databases, Pubmed, Embase, Web of Science, and Cochrane Library (CENTRAL), were searched for relevant literature from 2000–01 to 2023–03. Seven randomized controlled trials (RCTs) of fruit intake or fruit extracts associated with anti-skin aging were screened for Meta-analysis.ResultsCompared to placebo, oral intake of fruit or fruit extracts showed significant statistical differences in skin hydration and transepidermal water loss (TEWL), with a significant improvement in skin hydration and a significant decrease in TEWL. No significant statistical difference was observed in minimal erythema dose (MED), overall skin elasticity (R2), or wrinkle depth, and no evidence of significant improvement in skin condition was observed.ConclusionMeta-analysis results suggest that consume administration of fruits or fruit extracts significantly enhances skin hydration and reduces transcutaneous water loss, but there is insufficient evidence to support other outcome recommendations, including minimal erythema dose (MED), overall skin elasticity(R2), and wrinkle depth.
Systematic Review Registration
PROSPERO (york.ac.uk), identifier CRD42023410382.
A deep learning approach for automatic tumor delineation in stereotactic radiotherapy for non-small cell lung cancer using diagnostic PET-CT and planning CT
Authors: Yu Xuyao , He Lian , Wang Yuwen , Dong Yang , Song Yongchun , Yuan Zhiyong , Yan Ziye , Wang Wei 
Published: August 2023

IntroductionAccurate delineation of tumor targets is crucial for stereotactic body radiation therapy (SBRT) for non-small cell lung cancer (NSCLC). This study aims to develop a deep learning-based segmentation approach to accurately and efficiently delineate NSCLC targets using diagnostic PET-CT and SBRT planning CT (pCT).MethodsThe diagnostic PET was registered to pCT using the transform matrix from registering diagnostic CT to the pCT. We proposed a 3D-UNet-based segmentation method to segment NSCLC tumor targets on dual-modality PET-pCT images. This network contained squeeze-and-excitation and Residual blocks in each convolutional block to perform dynamic channel-wise feature recalibration. Furthermore, up-sampling paths were added to supplement low-resolution features to the model and also to compute the overall loss function. The dice similarity coefficient (DSC), precision, recall, and the average symmetric surface distances were used to assess the performance of the proposed approach on 86 pairs of diagnostic PET and pCT images. The proposed model using dual-modality images was compared with both conventional 3D-UNet architecture and single-modality image input.ResultsThe average DSC of the proposed model with both PET and pCT images was 0.844, compared to 0.795 and 0.827, when using 3D-UNet and nnUnet. It also outperformed using either pCT or PET alone with the same network, which had DSC of 0.823 and 0.732, respectively.DiscussionTherefore, our proposed segmentation approach is able to outperform the current 3D-UNet network with diagnostic PET and pCT images. The integration of two image modalities helps improve segmentation accuracy.