bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and validation of nomogram for unplanned ICU admission in patients with dilated cardiomyopathy
Authors: Li Xiao-Lei , Adi Dilare , Zhao Qian , Aizezi Aibibanmu , Keremu Munawaer , Li Yan-Peng , Liu Fen , Ma Xiang , Li Xiao-Mei , Azhati Adila , Ma Yi-Tong 
Published: March 2023

ObjectiveUnplanned admission to the intensive care unit (ICU) is the major in-hospital adverse event for patients with dilated cardiomyopathy (DCM). We aimed to establish a nomogram of individualized risk prediction for unplanned ICU admission in DCM patients.MethodsA total of 2,214 patients diagnosed with DCM from the First Affiliated Hospital of Xinjiang Medical University from January 01, 2010, to December 31, 2020, were retrospectively analyzed. Patients were randomly divided into training and validation groups at a 7:3 ratio. The least absolute shrinkage and selection operator and multivariable logistic regression analysis were used for nomogram model development. The area under the receiver operating characteristic curve, calibration curves, and decision curve analysis (DCA) were used to evaluate the model. The primary outcome was defined as unplanned ICU admission.ResultsA total of 209 (9.44%) patients experienced unplanned ICU admission. The variables in our final nomogram included emergency admission, previous stroke, New York Heart Association Class, heart rate, neutrophil count, and levels of N-terminal pro b-type natriuretic peptide. In the training group, the nomogram showed good calibration (Hosmer–Lemeshow χ2 = 14.40, P = 0.07) and good discrimination, with an optimal-corrected C-index of 0.76 (95% confidence interval: 0.72–0.80). DCA confirmed the clinical net benefit of the nomogram model, and the nomogram maintained excellent performances in the validation group.ConclusionThis is the first risk prediction model for predicting unplanned ICU admission in patients with DCM by simply collecting clinical information. This model may assist physicians in identifying individuals at a high risk of unplanned ICU admission for DCM inpatients.
Pattern and effect of economic agglomeration in the Yangtze River Delta region based on population-land allometric growth
Authors: Zhu Yiheng , Yang Shan , Lin Jinping , Cai Anning 
Published: March 2023

The speed of urban growth affects urban development’s momentum and urban agglomeration’s spatial state. The influence of the asymmetric flow of population and land factors on the economic agglomeration effect is an essential issue in the coordinated development of urbanization. To study its impact on the orderly development of China’s urban economy, this paper selects 41 cities in the Yangtze River Delta (YRD) region, measuring the spatial and temporal evolution of the allometric growth relationship between population and land, explores the mechanism of the effect of allometric relationships on the economic agglomeration effect. The results show that: 1) Population-land allometric growth is characterized by a transition from population to land expansion. The transition phase is divided into six stages, from positive to negative allometric growth. In terms of scaling coefficients, the period from 2000 to 2011 is characterized by negative allometric growth, and the period from 2012 to 2019 is characterized by positive allometric growth. Spatially, the Shanghai metropolitan area evolves into a positive allometric primary stage, while the core and central areas evolve into a positive allometric secondary stage, with the latter’s development transition lagging behind the former by about 10 years. 2) The spatial dependence of economic agglomeration in the Yangtze River Delta is strong, showing a spatial distribution trend of “high in the middle, low in the north and south, high in the east and low in the west,” the agglomeration gap is gradually reduced, forming a “continuous area of high-value economic agglomeration” with the core area as the center and spreading outward, reflecting the efficacy of the Yangtze River Delta integrated development strategy. 3) The economic agglomeration effect of allometric growth is classified into four types: positive-allometric positive-effect, positive-allometric negative-effect, negative-allometric positive-effect, and negative-allometric negative-effect. In the Yangtze River Delta region, 70.7% of the cities have positive effects, of which 93.1% are positive-positive. 4) The allometric growth has an important impact on the reconfiguration of economic agglomeration pattern, 78% of the cities in the study period produced leapfrog movements in different quadrants, and the incongruity between population growth and land expansion should be actively regulated in the future to promote the evolution of cities towards an intensive type of population-land coordination to lead the high-quality development of the regional economy.
The association between neutrophil counts and neutrophil-to-lymphocyte ratio and stress hyperglycemia in patients with acute ischemic stroke according to stroke etiology
Authors: Feng Xianjing , Yu Fang , Wei Minping , Luo Yunfang , Zhao Tingting , Liu Zeyu , Huang Qin , Tu Ruxin , Li Jiaxin , Zhang Boxin , Cheng Liuyang , Xia Jian 
Published: March 2023

Background and purposeStress hyperglycemia ratio (SHR), which is used to assess stress hyperglycemia, is associated with the functional outcome of ischemic stroke (IS). IS can induce the inflammatory response. Neutrophil counts and neutrophil-to-lymphocyte ratio (NLR) as good and easily available inflammatory biomarkers, the relationship between neutrophil counts and NLR and SHR were poorly explored in IS. We aimed to systemically and comprehensively explore the correlation between various blood inflammation markers (mainly neutrophil counts and NLR) and SHR.MethodsData from 487 patients with acute IS(AIS) in Xiangya Hospital were retrospectively reviewed. High/low SHR groups according to the median of SHR (≤1.02 versus &gt;1.02). Binary logistic regression analysis was used to evaluate the correlation between neutrophil counts and NLR and high SHR group. Subgroup analyses were performed in the TOAST classification and functional prognosis.ResultsThe neutrophil counts and NLR were all clearly associated with SHR levels in different logistic analysis models. In the subgroup analysis of TOAST classification, the higher neutrophil counts and NLR were the independent risk factors for high SHR patients with large-artery atherosclerosis (LAA) (neutrophil: adjusted OR:2.047, 95% CI: 1.355-3.093, P=0.001; NLR: adjusted OR:1.315, 95% CI: 1.129-1.530, P&lt;0.001). The higher neutrophil counts were the independent risk factor for high SHR patients with cardioembolism (CE) (adjusted OR:2.413, 95% CI: 1.081-5.383, P=0.031). ROC analysis showed that neutrophil counts was helpful for differentiating high SHR group with CE and low SHR group with CE (neutrophil: AUC =0.776, P=0.002). However, there were no difference in levels of neutrophil counts and NLR between patients with SVO and without SVO. The higher neutrophil counts and NLR independently associated with high SHR patients with mRS ≤2 at 90 days from symptom onset, (neutrophil: adjusted OR:2.284, 95% CI: 1.525-3.420, P&lt;0.001; NLR: adjusted OR:1.377, 95% CI: 1.164-1.629, P&lt;0.001), but not in patients with mRS &gt;2.ConclusionsThis study found that the neutrophil counts and NLR are positively associated with SHR levels in AIS patients. In addition, the correlation between neutrophil counts and NLR and different SHR levels are diverse according to TOAST classification and functional prognosis.
Distribution characteristics of oral microbiota and its relationship with intestinal microbiota in patients with type 2 diabetes mellitus
Authors: Guo Xiao-jing , Dai Shi-xuan , Lou Jin-di , Ma Xu-xiang , Hu Xiao-juan , Tu Li-ping , Cui Ji , Lu Hao , Jiang Tao , Xu Jia-tuo 
Published: March 2023

IntroductionType 2 diabetes mellitus (T2DM) has a high incidence rate globally, increasing the burden of death, disability, and the economy worldwide. Previous studies have found that the compositions of oral and intestinal microbiota changed respectively in T2DM; whether the changes were associated or interacted between the two sites and whether there were some associations between T2DM and the ectopic colonization of oral microbiota in the gut still need to be identified.Research design and methodsWe performed a cross-sectional observational study; 183 diabetes and 74 controls were enrolled. We used high-throughput sequencing technology to detect the V3-V4 region of 16S rRNA in oral and stool samples. The Source Tracker method was used to identify the proportion of the intestinal microbiota that ectopic colonized from the oral cavity.ResultsThe oral marker bacteria of T2DM were found, such as Actinobacteria, Streptococcus, Rothia, and the intestinal marker bacteria were Bifidobacterium, Streptococcus, and Blautia at the genus level. Among them, Actinobacteria and Blautia played a vital role in different symbiotic relationships of oral and intestinal microbiota. The commonly distributed bacteria, such as Firmicutes, Bacteroidetes, and Actinobacteria, were found in both oral and intestine. Moreover, the relative abundance and composition of bacteria were different between the two sites. The glycine betaine degradation I pathway was the significantly up-regulated pathway in the oral and intestinal flora of T2DM. The main serum indexes related to oral and intestinal flora were inflammatory. The relative abundance of Proteobacteria in the intestine and the Spirochete in oral was positively correlated, and the correlation coefficient was the highest, was 0.240 (P&lt;0.01). The proportion of ectopic colonization of oral flora in the gut of T2DM was 2.36%.ConclusionThe dysbacteriosis exited in the oral and intestine simultaneously, and there were differences and connections in the flora composition at the two sites in T2DM. Ectopic colonization of oral flora in the intestine might relate to T2DM. Further, clarifying the oral-gut-transmitting bacteria can provide an essential reference for diagnosing and treating T2DM in the future.
The length of FOXE1 polyalanine tract in congenital hypothyroidism: Evidence for a pathogenic role from familial, molecular and cohort studies
Authors: Grassi Elisa Stellaria , Rurale Giuditta , de Filippis Tiziana , Gentilini Davide , Carbone Erika , Coscia Francesca , Uraghi Sarah , Bullock Martyn , Clifton-Bligh Roderick J. , Gupta Abhinav K. , Persani Luca 
Published: March 2023

IntroductionFOXE1 is required for thyroid function and its homozygous mutations cause a rare syndromic form of congenital hypothyroidism (CH). FOXE1 has a polymorphic polyalanine tract whose involvement in thyroid pathology is controversial. Starting from genetic studies in a CH family, we explored the functional role and involvement of FOXE1 variations in a large CH population.MethodsWe applied NGS screening to a large CH family and a cohort of 1752 individuals and validated these results by in silico modeling and in vitro experiments.ResultsA new heterozygous FOXE1 variant segregated with 14-Alanine tract homozygosity in 5 CH siblings with athyreosis. The p.L107V variant demonstrated to significantly reduce the FOXE1 transcriptional activity. The 14-Alanine-FOXE1 displayed altered subcellular localization and significantly impaired synergy with other transcription factors, when compared with the more common 16-Alanine-FOXE1. The CH group with thyroid dysgenesis was largely and significantly enriched with the 14-Alanine-FOXE1 homozygosity.DiscussionWe provide new evidence that disentangle the pathophysiological role of FOXE1 polyalanine tract, thereby significantly broadening the perspective on the role of FOXE1 in the complex pathogenesis of CH. FOXE1 should be therefore added to the group of polyalanine disease-associated transcription factors.
Effects of hypoxia-inducible factor-prolyl hydroxylase inhibitors vs. erythropoiesis-stimulating agents on iron metabolism in non-dialysis-dependent anemic patients with CKD: A network meta-analysis
Authors: Yang Junlan , Xing Jie , Zhu Xiaodong , Xie Xiaotong , Wang Lina , Zhang Xiaoliang 
Published: March 2023

ObjectiveTo compare the effects of five hypoxia-inducible factor-prolyl hydroxylase domain inhibitors (HIF-PHIs), two erythropoiesis-stimulating agents (ESAs), and placebo on iron metabolism in renal anemia patients with non-dialysis-dependent chronic kidney disease (NDD-CKD).MethodFive electronic databases were searched for studies. Randomized controlled clinical trials comparing HIF-PHIs, ESAs, and placebo in NDD-CKD patients were selected. The statistical program used for network meta-analysis was Stata/SE 15.1. The main outcomes were the change in hepcidin and hemoglobin (Hb) levels. The merits of intervention measures were predicted by the surface under the cumulative ranking curve method.ResultsOf 1,589 original titles screened, data were extracted from 15 trials (3,228 participants). All HIF-PHIs and ESAs showed greater Hb level–raising ability than placebo. Among them, desidustat demonstrated the highest probability of increasing Hb (95.6%). Hepcidin [mean deviation (MD) = -43.42, 95%CI: -47.08 to -39.76], ferritin (MD= -48.56, 95%CI: -55.21 to -41.96), and transferrin saturation (MD = -4.73, 95%CI: -5.52 to -3.94) were decreased, while transferrin (MD = 0.09, 95%CI: 0.01 to 0.18) and total iron-binding capacity (MD = 6.34, 95%CI: 5.71 to 6.96) was increased in HIF-PHIs versus those in ESAs. In addition, this study observed heterogeneity in the ability of HIF-PHIs to decrease hepcidin. Compared with darbepoetin, only daprodustat (MD = –49.09, 95% CI: –98.13 to –0.05) could significantly reduce hepcidin levels. Meanwhile, daprodustat also showed the highest hepcidin-lowering efficacy (84.0%), while placebo was the lowest (8.2%).ConclusionFor NDD-CKD patients, HIF-PHIs could ameliorate functional iron deficiency by promoting iron transport and utilization, which may be achieved by decreasing hepcidin levels. Interestingly, HIF-PHIs had heterogeneous effects on iron metabolism.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=242777, Identifier CRD42021242777.
Endometrial stromal cell miR-19b-3p release is reduced during decidualization implying a role in decidual-trophoblast cross-talk
Authors: Menkhorst Ellen , So Teresa , Rainczuk Kate , Barton Siena , Zhou Wei , Edgell Tracey , Dimitriadis Evdokia 
Published: March 2023

IntroductionA healthy pregnancy requires successful blastocyst implantation into an adequately prepared or ‘receptive’ endometrium. Decidualization of uterine endometrial stromal fibroblast cells (hESF) is critical for the establishment of a healthy pregnancy. microRNAs (miRs) are critical regulators of cellular function that can be released by a donor cell to influence the physiological state of recipient cells. We aimed to determine how decidualization affects hESF miR release and investigated the function of one decidualization regulated miR, miR-19b-3p, previously shown to be associated with recurrent pregnancy loss.MethodmiR release by hESF was determined by miR microarray on culture media from hESF decidualized in vitro for 3 and 14 days by treatment with oestradiol and medroxyprogesterone acetate. Cellular and whole endometrial/decidual tissue miR expression was quantified by qPCR and localized by in situ hybridization. The function of miR-19b-3p in HTR8/Svneo trophoblast cells was investigated using real time cell analysis (xCELLigence) and gene expression qPCR.ResultsFrom our miR screen we found that essentially all hESF miR release was reduced following in vitro decidualization, significantly so for miR-17-5p, miR-21-3p, miR-34c-3p, miR-106b-5p, miR-138-5p, miR-296-5p, miR-323a-3p, miR-342-3p, miR-491-5p, miR-503-5p and miR-542-5p. qPCR demonstrated that miR-19b-3p, 181a-2-3p and miR-409-5p likewise showed a significant reduction in culture media following decidualization but no change was found in cellular miR expression following decidualization. In situ hybridization localized miR-19b-3p to epithelial and stromal cells in the endometrium and qPCR identified that miR-19b-3p was significantly elevated in the cycling endometrium of patients with a history of early pregnancy loss compared to normally fertile controls. Functionally, overexpression of miR-19b-3p significantly reduced HTR8/Svneo trophoblast proliferation and increased HOXA9 expression.DiscussionOur data demonstrates that decidualization represses miR release by hESFs and overexpression of miR-19b-3p was found in endometrial tissue from patients with a history of early pregnancy loss. miR-19b-3p impaired HTR8/Svneo proliferation implying a role in trophoblast function. Overall we speculate that miR release by hESF may regulate other cell types within the decidua and that appropriate release of miRs by decidualized hESF is essential for healthy implantation and placentation.
Genetic mapping identifies genomic regions and candidate genes for seed weight and shelling percentage in groundnut
Authors: Gangurde Sunil S. , Pasupuleti Janila , Parmar Sejal , Variath Murali T. , Bomireddy Deekshitha , Manohar Surendra S. , Varshney Rajeev K. , Singam Prashant , Guo Baozhu , Pandey Manish K. 
Published: March 2023

Seed size is not only a yield-related trait but also an important measure to determine the commercial value of groundnut in the international market. For instance, small size is preferred in oil production, whereas large-sized seeds are preferred in confectioneries. In order to identify the genomic regions associated with 100-seed weight (HSW) and shelling percentage (SHP), the recombinant inbred line (RIL) population (Chico × ICGV 02251) of 352 individuals was phenotyped for three seasons and genotyped with an Axiom_Arachis array containing 58K SNPs. A genetic map with 4199 SNP loci was constructed, spanning a map distance of 2708.36 cM. QTL analysis identified six QTLs for SHP, with three consistent QTLs on chromosomes A05, A08, and B10. Similarly, for HSW, seven QTLs located on chromosomes A01, A02, A04, A10, B05, B06, and B09 were identified. BIG SEED locus and spermidine synthase candidate genes associated with seed weight were identified in the QTL region on chromosome B09. Laccase, fibre protein, lipid transfer protein, senescence-associated protein, and disease-resistant NBS-LRR proteins were identified in the QTL regions associated with shelling percentage. The associated markers for major-effect QTLs for both traits successfully distinguished between the small- and large-seeded RILs. QTLs identified for HSW and SHP can be used for developing potential selectable markers to improve the cultivars with desired seed size and shelling percentage to meet the demands of confectionery industries.
A chemokine network of T cell exhaustion and metabolic reprogramming in renal cell carcinoma
Authors: Pichler Renate , Siska Peter J. , Tymoszuk Piotr , Martowicz Agnieszka , Untergasser Gerold , Mayr Roman , Weber Florian , Seeber Andreas , Kocher Florian , Barth Dominik A. , Pichler Martin , Thurnher Martin 
Published: March 2023

Renal cell carcinoma (RCC) is frequently infiltrated by immune cells, a process which is governed by chemokines. CD8+ T cells in the RCC tumor microenvironment (TME) may be exhausted which most likely influence therapy response and survival. The aim of this study was to evaluate chemokine-driven T cell recruitment, T cell exhaustion in the RCC TME, as well as metabolic processes leading to their functional anergy in RCC. Eight publicly available bulk RCC transcriptome collectives (n=1819) and a single cell RNAseq dataset (n=12) were analyzed. Immunodeconvolution, semi-supervised clustering, gene set variation analysis and Monte Carlo-based modeling of metabolic reaction activity were employed. Among 28 chemokine genes available,CXCL9/10/11/CXCR3, CXCL13/CXCR5 and XCL1/XCR1mRNA expression were significantly increased in RCC compared to normal kidney tissue and also strongly associated with tumor-infiltrating effector memory and central memory CD8+T cells in all investigated collectives. M1 TAMs, T cells, NK cells as well as tumor cells were identified as the major sources of these chemokines, whereas T cells, B cells and dendritic cells were found to predominantly express the cognate receptors. The cluster of RCCs characterized by high chemokine expression and high CD8+T cell infiltration displayed a strong activation of IFN/JAK/STAT signaling with elevated expression of multiple T cell exhaustion-associated transcripts. ChemokinehighRCCs were characterized by metabolic reprogramming, in particular by downregulated OXPHOS and increased IDO1-mediated tryptophan degradation. None of the investigated chemokine genes was significantly associated with survival or response to immunotherapy. We propose a chemokine network that mediates CD8+T cell recruitment and identify T cell exhaustion, altered energy metabolism and high IDO1 activity as key mechanisms of their suppression. Concomitant targeting of exhaustion pathways and metabolism may pose an effective approach to RCC therapy.
COVID-19 vaccination in psoriasis patients receiving systemic treatment: A prospective single-center study
Authors: Lodde Georg Christian , Krefting Frederik , Placke Jan-Malte , Schneider Lea , Fiedler Melanie , Dittmer Ulf , Becker Jürgen Christian , Hölsken Stefanie , Schadendorf Dirk , Ugurel Selma , Sondermann Wiebke 
Published: March 2023

BackgroundThe rate of seroconversion after COVID-19 vaccination in patients with moderate to severe psoriasis requiring systemic treatment is poorly understood.ObjectivesThe aim of this prospective single-center cohort study performed between May 2020 and October 2021 was to determine the rate of seroconversion after COVID-19 vaccination in patients under active systemic treatment for moderate to severe psoriasis.MethodsInclusion criteria were systemic treatment for moderate to severe psoriasis, known COVID-19 vaccination status, and repetitive anti-SARS-CoV-2-S IgG serum quantification. The primary outcome was the rate of anti-SARS-CoV-2-S IgG seroconversion after complete COVID-19 vaccination.Results77 patients with a median age of 55.9 years undergoing systemic treatment for moderate to severe psoriasis were included. The majority of patients received interleukin- (n=50, 64.9%) or tumor necrosis factor (TNF)-α inhibitors (n=16, 20.8%) as systemic treatment for psoriasis; nine patients (11.7%) were treated with methotrexate (MTX) monotherapy, and one patient each received dimethyl fumarate (1.3%), respectively apremilast (1.3%). All included patients completed COVID-19 vaccination with two doses over the course of the study. Serum testing revealed that 74 patients (96.1%) showed an anti-SARS-CoV-2-S IgG seroconversion. While all patients on IL-17A, -12 or -12/23 inhibitors (n=50) achieved seroconversion, three of 16 patients (18.8%) receiving MTX and/or a TNF-α inhibitor as main anti-psoriatic treatment did not. At follow-up, none of the patients had developed symptomatic COVID-19 or died from COVID-19.ConclusionsAnti-SARS-CoV-2-S IgG seroconversion rates following COVID-19 vaccination in psoriasis patients under systemic treatment were high. An impaired serological response, however, was observed in patients receiving MTX and/or TNF-α inhibitors, in particular infliximab.