bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sin3a associated protein 130 kDa, sap130, plays an evolutionary conserved role in zebrafish heart development
Authors: DeMoya Ricardo A. , Forman-Rubinsky Rachel E. , Fontaine Deon , Shin Joseph , Watkins Simon C. , Lo Cecilia W. , Tsang Michael 
Published: August 2023

Hypoplastic left heart syndrome (HLHS) is a congenital heart disease where the left ventricle is reduced in size. A forward genetic screen in mice identified SIN3A associated protein 130 kDa (Sap130), part of the chromatin modifying SIN3A/HDAC complex, as a gene contributing to the etiology of HLHS. Here, we report the role of zebrafish sap130 genes in heart development. Loss of sap130a, one of two Sap130 orthologs, resulted in smaller ventricle size, a phenotype reminiscent to the hypoplastic left ventricle in mice. While cardiac progenitors were normal during somitogenesis, diminution of the ventricle size suggest the Second Heart Field (SHF) was the source of the defect. To explore the role of sap130a in gene regulation, transcriptome profiling was performed after the heart tube formation to identify candidate pathways and genes responsible for the small ventricle phenotype. Genes involved in cardiac differentiation and cardiac function were dysregulated in sap130a, but not in sap130b mutants. Confocal light sheet analysis measured deficits in cardiac output in MZsap130a supporting the notion that cardiomyocyte maturation was disrupted. Lineage tracing experiments revealed a significant reduction of SHF cells in the ventricle that resulted in increased outflow tract size. These data suggest that sap130a is involved in cardiogenesis via regulating the accretion of SHF cells to the growing ventricle and in their subsequent maturation for cardiac function. Further, genetic studies revealed an interaction between hdac1 and sap130a, in the incidence of small ventricles. These studies highlight the conserved role of Sap130a and Hdac1 in zebrafish cardiogenesis.
A 7-year review of clinical characteristics, predisposing factors and outcomes of post-keratoplasty infectious keratitis: the Nottingham infectious keratitis study
Authors: Ong Zun Zheng , Wong Thai Ling , Suresh Lakshmi , Hammoudeh Yasmeen , Lister Michelle , Said Dalia G. , Dua Harminder S. , Ting Darren S. J. 
Published: August 2023

Background/objectivesPost-keratoplasty infectious keratitis (PKIK) is a unique sight-threatening clinical entity which often poses significant therapeutic challenges. This study aimed to examine the clinical presentation, risk factors, management, and clinical outcomes of PKIK.MethodsThis was a retrospective study of all patients who presented to the Queen’s Medical Centre, Nottingham, with PKIK between September 2015 and August 2022 (a 7-year period). Relevant data on types of keratoplasty, clinical presentations, causative microorganisms, management, and outcome were analyzed.ResultsForty-nine PKIK cases, including four cases of interface infectious keratitis, were identified during the study period. The most common graft indications for PKP, DALK and EK were failed grafts (9, 37.5%), keratoconus (6, 54.5%) and Fuchs endothelial corneal dystrophy (FECD; 8, 57.1%), respectively. Staphylococcus spp. were the most commonly identified organisms (15, 50.0%). Bullous keratopathy (18, 36.7%), ocular surface disease (18, 36.7%), and broken/loose sutures (15, 30.6%) were the most common risk factors. Concurrent use of topical steroids was identified in 25 (51.0%) cases. Of 31 functioning grafts at presentation, 12 (38.7%) grafts failed at final follow-up with 15 (48.4%) patients retaining a CDVA of ≥1.0 logMAR. The overall estimated 5-year survival rate post-PKIK was 55.9% (95% CI, 35.9%-75.9%), with DALK having the highest survival rate [63.6% (95% CI, 28.9%-98.3%)], followed by EK [57.1% (95% CI, 20.4%-93.8%)] and PKP [52.7% (95% CI, 25.1%-80.3%)], though no statistical difference was observed (p=0.48).ConclusionsPKIK represents an important cause of IK and graft failure. Bullous keratopathy, OSD and suture-related complications are the commonest risk factors, highlighting the potential benefit of prophylactic topical antibiotics (for unhealthy ocular surface) and early suture removal (where possible) in reducing the risk of PKIK. Graft survival may be higher in lamellar keratoplasty following PKIK but larger studies are required to elucidate this observation.
Quantitative flow ratio-based outcomes in patients undergoing transcatheter aortic valve implantation quaestio study
Authors: Demola Pierluigi , Colaiori Iginio , Bosi Davide , Musto D’Amore Sergio , Vitolo Marco , Benatti Giorgio , Vignali Luigi , Tadonio Iacopo , Gabbieri Davide , Losi Luciano , Magnavacchi Paolo , Sgura Fabio Alfredo , Boriani Giuseppe , Guiducci Vincenzo 
Published: August 2023

BackgroundCoronary artery disease (CAD) is common in patients with aortic valve stenosis (AS) ranging from 60% to 80%. The clinical and prognostic role of coronary artery lesions in patients undergoing Transcatheter Aortic Valve Implantation (TAVI) remains unclear. The aim of the present observational study was to estimate long-term clinical outcomes by Quantitative Flow Ratio (QFR) characterization of CAD in a well-represented cohort of patients affected by severe AS treated by TAVI.MethodsA total of 439 invasive coronary angiographies of patients deemed eligible for TAVI by local Heart Teams with symptomatic severe AS were retrospectively screened for QFR analysis. The primary endpoint of the study was all-cause mortality. The secondary endpoint was a composite of cardiovascular mortality, stroke/transient ischemic attack (TIA), acute myocardial infarction (AMI), and any hospitalization after TAVI.ResultsAfter exclusion of patients with no follow-up data, coronary angiography not feasible for QFR analysis and previous surgical myocardial revascularization (CABG) 48/239 (20.1%) patients had a QFR value lower or equal to 0.80 (QFR + value), while the remaining 191/239 (79.9%) did not present any vessel with a QFR positive value. In the adjusted Cox regression analysis, patients with positive QFR were independently associated with an increased risk of all-casual mortality (Model 1, HR 3.47, 95% CI, 2.35−5.12; Model 2, HR 5.01, 95% CI, 3.17−7.90). In the adjusted covariate analysis, QFR+ involving LAD (37/48, 77,1%) was associated with the higher risk of the composite outcome compared to patients without any positive value of QFR or non-LAD QFR positive value (11/48, 22.9%).ConclusionsPre-TAVI QFR analysis can be used for a safe, simple, wireless functional assessment of CAD. QFR permits to identify patients at high risk of cardiovascular mortality or MACE, and it could be considered by local Heart Teams.
The association of central and extremity circumference with all-cause mortality and cardiovascular mortality: a cohort study
Authors: Liu Jiajun , Jin Xueshan , Feng Ziyi , Huang Jieming 
Published: August 2023

BackgroundCentral obesity increases the risk of several diseases, including diabetes, cardiovascular disease (CVD), and cancer. However, the association between extremity obesity and mortality has not been extensively evaluated. The objective of this study was to investigate the quantitative effects of waist circumference (WC), arm circumference (AC), calf circumference (CC), and thigh circumference (TC) on all-cause mortality and CVD mortality.MethodsThe study used data from the National Health and Nutrition Examination Survey (NHANES) sample survey from 1999 to 2006. A total of 19,735 participants were included in the study. We divided the participants into four groups (Q1–Q4) and used Q1 as a reference to compare the risk of all-cause mortality and CVD mortality in Q2–Q4. COX proportional hazard regression model was used to analyze the relationship between WC, AC, CC and TC on all-cause and CVD mortality. In addition, we conducted a stratified analysis of gender.ResultsAfter a mean follow-up of 11.8 years, we observed a total of 3,446 deaths, of which 591 were due to cardiovascular disease. The results showed that for both men and women, compared to the first group, the risk of all-cause mortality was significantly higher in the other three groups of WC and significantly lower in the other three groups of AC, CC, and TC. Similar results were observed after adjusting for confounding factors such as demographics.ConclusionsOur results show that all-cause and CVD mortality are positively associated with measures of central obesity and negatively associated with measures of extremity obesity, and that AC, CC, and TC can be used as potential tools to measure prognosis in the general population.
An investigation on the thixotropic parameters and mechanical properties of loess
Authors: Wei Le , Dang Faning , Ding Jiulong 
Published: August 2023

The analysis of thixotropic mechanical properties of loess has a significant influence on the calculation of the strength of compacted loess foundation. In order to distinguish the consolidation growth strength of loess from the thixotropic strength, a resting thixotropic instrument is developed. The proposed device is capable of maintaining a constant volume pressure. To attain the goals, after selecting the representative Xi’an loess, the samples were pressed by the resting thixotropic instrument under constant volume pressure. Eight resting ages were also set. Moreover, the thixotropic mechanical properties of loess soil were studied at 6 months resting ages through uniaxial compression without lateral limit and triaxial CU test. The thixotropic triaxial shear strength ratio Jt, thixotropic triaxial shear strength recovery ratio Kt and thixotropic cohesion recovery ratio Lt were defined, the mechanical properties of which were investigated under different stress states. The obtained results demonstrated the obvious thixotropy of Xi’an loess, the strength of which was found to increase with an increase in the resting age. This is while, an increase in the resting age was observed to decrease the its growth rate. Moreover, the unconfined thixotropic strength was found to increase by 1.75 times after resting for 160d, which corroborates the influence of thixotropic strength in designing the foundation bearing capacity of loess. Furthermore, the recovery ratio of unconfined thixotropic strength and the growth ratio of eccentric stress strength were found to be 0.187 and 0.115, respectively. In addition, the thixotropic triaxial shear strength ratio Jt, the recovery ratio of thixotropic triaxial shear strength ratio Kt, and the recovery ratio of thixotropic cohesion ratio Lt were observed to be 0.15, 0.527, and 0.5, respectively. The obtained results suggest the resting age of 40 days to be used as the inflection point for the recovery of thixotropic strength such as uniaxial compressive strength, peak deviator stress, shear strength and cohesion of loess. Despite the insignificant variation range of the friction Angle in the resting process, the contribution ratio of friction force in increasing the shear strength was also found to be much greater than that of the cohesion.
Satellite-based estimation of soil organic carbon in Portuguese grasslands
Authors: Morais Tiago G. , Jongen Marjan , Tufik Camila , Rodrigues Nuno R. , Gama Ivo , Serrano João , Gonçalves Maria C. , Mano Raquel , Domingos Tiago , Teixeira Ricardo F. M. 
Published: August 2023

Introduction:Soil organic carbon (SOC) sequestration is one of the main ecosystem services provided by well-managed grasslands. In the Mediterranean region, sown biodiverse pastures (SBP) rich in legumes are a nature-based, innovative, and economically competitive livestock production system. As a co-benefit of increased yield, they also contribute to carbon sequestration through SOC accumulation. However, SOC monitoring in SBP require time-consuming and costly field work.Methods:In this study, we propose an expedited and cost-effective indirect method to estimate SOC content. In this study, we developed models for estimating SOC concentration by combining remote sensing (RS) and machine learning (ML) approaches. We used field-measured data collected from nine different farms during four production years (between 2017 and 2021). We utilized RS data from both Sentinel-1 and Sentinel-2, including reflectance bands and vegetation indices. We also used other covariates such as climatic, soil, and terrain variables, for a total of 49 inputs. To reduce multicollinearity problems between the different variables, we performed feature selection using the sequential feature selection approach. We then estimated SOC content using both the complete dataset and the selected features. Multiple ML methods were tested and compared, including multiple linear regression (MLR), random forests (RF), extreme gradient boosting (XGB), and artificial neural networks (ANN). We used a random cross-validation approach (with 10 folds). To find the hyperparameters that led to the best performance, we used a Bayesian optimization approach.Results:Results showed that the XGB method led to higher estimation accuracy than the other methods, and the estimation performance was not significantly influenced by the feature selection approach. For XGB, the average root mean square error (RMSE), measured on the test set among all folds, was 2.78 g kg−1(r2equal to 0.68) without feature selection, and 2.77 g kg−1(r2equal to 0.68) with feature selection (average SOC content is 13 g kg−1). The models were applied to obtain SOC content maps for all farms.Discussion:This work demonstrated that combining RS and ML can help obtain quick estimations of SOC content to assist with SBP management.
Exploring novel genetic and hematological predictors of response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer
Authors: Marinkovic Mladen , Stojanovic-Rundic Suzana , Stanojevic Aleksandra , Ostojic Marija , Gavrilovic Dusica , Jankovic Radmila , Maksimovic Natasa , Stroggilos Rafael , Zoidakis Jerome , Castellví-Bel Sergi , Fijneman Remond J. A. , Cavic Milena 
Published: August 2023

Introduction: The standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (nCRT). To select patients who would benefit the most from nCRT, there is a need for predictive biomarkers. The aim of this study was to evaluate the role of clinical, pathological, radiological, inflammation-related genetic, and hematological parameters in the prediction of post-nCRT response.Materials and methods:In silico analysis of published transcriptomics datasets was conducted to identify candidate genes, whose expression will be measured using quantitative Real Time PCR (qRT-PCR) in pretreatment formaline-fixed paraffin-embedded (FFPE) samples. In this study, 75 patients with LARC were prospectively included between June 2020—January 2022. Patients were assessed for tumor response in week 8 post-nCRT with pelvic MRI scan and rigid proctoscopy. For patients with a clinical complete response (cCR) and initially distant located tumor no immediate surgery was suggested (“watch and wait” approach). The response after surgery was assessed using histopathological tumor regression grading (TRG) categories from postoperative specimens by Mandard. Responders (R) were defined as patients with cCR without operative treatment, and those with TRG 1 and TRG 2 postoperative categories. Non-responders (NR) were patients classified as TRG 3-5.Results: Responders group comprised 35 patients (46.6%) and NR group 53.4% of patients. Analysis of published transcriptomics data identified genes that could predict response to treatment and their significance was assessed in our cohort by qRT-PCR. When comparison was made in the subgroup of patients who were operated (TRG1 vs. TRG4), the expression of IDO1 was significantly deregulated (p &lt; 0.05). Among hematological parameters between R and NR a significant difference in the response was detected for neutrophil-to-monocyte ratio (NMR), initial basophil, eosinophil and monocyte counts (p &lt; 0.01). According to MRI findings, non-responders more often presented with extramural vascular invasion (p &lt; 0.05).Conclusion: Based on logistic regression model, factors associated with favorable response to nCRT were tumor morphology and hematological parameters which can be easily and routinely derived from initial laboratory results (NMR, eosinophil, basophil and monocyte counts) in a minimally invasive manner. Using various metrics, an aggregated score of the initial eosinophil, basophil, and monocyte counts demonstrated the best predictive performance.
Changes in subcutaneous white adipose tissue cellular composition and molecular programs underlie glucose intolerance in persons with HIV
Authors: Bailin Samuel S. , Kropski Jonathan A. , Gangula Rama D. , Hannah LaToya , Simmons Joshua D. , Mashayekhi Mona , Ye Fei , Fan Run , Mallal Simon , Warren Christian M. , Kalams Spyros A. , Gabriel Curtis L. , Wanjalla Celestine N. , Koethe John R. 
Published: August 2023

IntroductionSubcutaneous adipose tissue (SAT) is a critical regulator of systemic metabolic homeostasis. Persons with HIV (PWH) have an increased risk of metabolic diseases and significant alterations in the SAT immune environment compared with the general population.MethodsWe generated a comprehensive single-cell multi-omic SAT atlas to characterize cellular compositional and transcriptional changes in 59 PWH across a spectrum of metabolic health. ResultsGlucose intolerance was associated with increased lipid-associated macrophages, CD4+ and CD8+ T effector memory cells, and decreased perivascular macrophages. We observed a coordinated intercellular regulatory program which enriched for genes related to inflammation and lipid-processing across multiple cell types as glucose intolerance increased. Increased CD4+ effector memory tissue-resident cells most strongly associated with altered expression of adipocyte genes critical for lipid metabolism and cellular regulation. Intercellular communication analysis demonstrated enhanced pro-inflammatory and pro-fibrotic signaling between immune cells and stromal cells in PWH with glucose intolerance compared with non-diabetic PWH. Lastly, while cell type-specific gene expression among PWH with diabetes was globally similar to HIV-negative individuals with diabetes, we observed substantially divergent intercellular communication pathways.DiscussionThese findings suggest a central role of tissue-resident immune cells in regulating SAT inflammation among PWH with metabolic disease, and underscore unique mechanisms that may converge to promote metabolic disease.
MiRNA 106a-5p in cerebrospinal fluid as signature of early relapsing remitting multiple sclerosis: a cross sectional study
Authors: Zanghì Aurora , Manuti Virginia , Serviddio Gaetano , D’Amico Emanuele , Avolio Carlo 
Published: August 2023

BackgroundCirculating microRNAs (MiRNAs) have been investigated for their role in fine-tuning the adaptive immune response to inflammatory factors and in Multiple Sclerosis (MS). They have been investigated as possible biomarkers for the diagnosis and prognosis of the disease.MethodsA cross sectional study conducted at the MS centre of Foggia, Italy. We enrolled patients with (1) an age between 18 and 55 years, (2) a definitive diagnosis of relapsing remitting MS (RRMS) as per the revised McDonald criteria, and (3) naïve to any disease modifying therapy (DMTs), as well as (4) patients with other neurological disorders (OND). The aim of the study was to compare the levels of expression of miRNA 21-5p, miRNA 106a-5p, miRNA 146a-5p, and miRNA223-3p in cell-free cerebrospinal fluid (CSF) in RRMS patients and OND. Investigated MiRNAs were extracted, retrotranscribed, and then assessed by real-time polymerase chain reaction assay (q-PCR). A receiver-operator characteristic (ROC) curve was used to test MiRNAs as a biomarker for diagnosing MS. A linear regression analysis was done to find any association with disease characteristics at the time of diagnosis.ResultsA total cohort of 70 subjects (70% women) was analyzed. Out of them, 35 had a RRMS diagnosis. MiRNA 106a-5p (7.8 ± 3.8 vs 1.3 ± 0.9, p=0.03) had higher levels in RRMS patients when compared to OND. The ROC curve indicated that MiRNA 106a-5p could be considered as a disease biomarker with an area under the curve of 0.812 (p&lt;.001; 95% CI 0.686-0.937). Linear regression analysis showed an association between the number of oligoclonal bands and MiRNA 106a-5p levels (B-coeff 2.6, p&lt;.001; 95% CI 1.3-4.9).ConclusionWe described miRNA 106a-5p as a possible signature in the CSF of RRMS patients in early phases of the disease. Further studies are needed to characterize its role in early MS as a disease biomarker.
Identification of the shared mechanisms and common biomarkers between Sjögren’s syndrome and atherosclerosis using integrated bioinformatics analysis
Authors: Qi Xiaoyi , Huang Qianwen , Wang Shijia , Qiu Liangxian , Chen Xiongbiao , Ouyang Kunfu , Chen Yanjun 
Published: August 2023

BackgroundSjögren’s syndrome (SS) is a chronic autoimmune disease characterized by exocrine and extra-glandular symptoms. The literature indicates that SS is an independent risk factor for atherosclerosis (AS); however, its pathophysiological mechanism remains undetermined. This investigation aimed to elucidate the crosstalk genes and pathways influencing the pathophysiology of SS and AS via bioinformatic analysis of microarray data.MethodsMicroarray datasets of SS (GSE40611) and AS (GSE28829) were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were acquired using R software’s “limma” packages, and the functions of common DEGs were determined using Gene Ontology and Kyoto Encyclopedia analyses. The protein–protein interaction (PPI) was established using the STRING database. The hub genes were assessed via cytoHubba plug-in and validated by external validation datasets (GSE84844 for SS; GSE43292 for AS). Gene set enrichment analysis (GSEA) and immune infiltration of hub genes were also conducted.ResultsEight 8 hub genes were identified using the intersection of four topological algorithms in the PPI network. Four genes (CTSS, IRF8, CYBB, and PTPRC) were then verified as important cross-talk genes between AS and SS with an area under the curve (AUC) ≥0.7. Furthermore, the immune infiltration analysis revealed that lymphocytes and macrophages are essentially linked with the pathogenesis of AS and SS. Moreover, the shared genes were enriched in multiple metabolisms and autoimmune disease-related pathways, as evidenced by GSEA analyses.ConclusionThis is the first study to explore the common mechanism between SS and AS. Four key genes, including CTSS, CYBB, IRF8, and PTPRC, were associated with the pathogenesis of SS and AS. These hub genes and their correlation with immune cells could be a potential diagnostic and therapeutic target.