bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regeneration of Subcutaneous Cartilage in a Swine Model Using Autologous Auricular Chondrocytes and Electrospun Nanofiber Membranes Under Conditions of Varying Gelatin/PCL Ratios
Authors: Zheng Rui , Wang Xiaoyun , Xue Jixin , Yao Lin , Wu Gaoyang , Yi Bingcheng , Hou Mengjie , Xu Hui , Zhang Ruhong , Chen Jie , Shen Zhengyu , Liu Yu , Zhou Guangdong 
Published: December 2021

The scarcity of ideal biocompatible scaffolds makes the regeneration of cartilage in the subcutaneous environment of large animals difficult. We have previously reported the successful regeneration of good-quality cartilage in a nude mouse model using the electrospun gelatin/polycaprolactone (GT/PCL) nanofiber membranes. The GT/PCL ratios were varied to generate different sets of membranes to conduct the experiments. However, it is unknown whether these GT/PCL membranes can support the process of cartilage regeneration in an immunocompetent large animal model. We seeded swine auricular chondrocytes onto different GT/PCL nanofiber membranes (GT:PCL = 30:70, 50:50, and 70:30) under the sandwich cell-seeding mode. Prior to subcutaneously implanting the samples into an autologous host, they were cultured in vitro over a period of 2 weeks. The results revealed that the nanofiber membranes with different GT/PCL ratios could support the process of subcutaneous cartilage regeneration in an autologous swine model. The maximum extent of homogeneity in the cartilage tissues was achieved when the G5P5 (GT: PC = 50: 50) group was used for the regeneration of cartilage. The formed homogeneous cartilage tissues were characterized by the maximum cartilage formation ratio. The extents of the ingrowth of the fibrous tissues realized and the extents of infiltration of inflammatory cells achieved were found to be the minimum in this case. Quantitative analyses were conducted to determine the wet weight, cartilage-specific extracellular matrix content, and Young’s modulus. The results indicated that the optimal extent of cartilage formation was observed in the G5P5 group. These results indicated that the GT/PCL nanofiber membranes could serve as a potential scaffold for supporting subcutaneous cartilage regeneration under clinical settings. An optimum GT/PCL ratio can promote cartilage formation.
The Role of Cardiovascular Magnetic Resonance Imaging in the Assessment of Myocardial Fibrosis in Young and Veteran Athletes: Insights From a Meta-Analysis
Authors: Androulakis Emmanuel , Mouselimis Dimitrios , Tsarouchas Anastasios , Antonopoulos Alexios , Bakogiannis Constantinos , Papagkikas Panagiotis , Vlachopoulos Charalambos 
Published: December 2021

Background: Cardiac magnetic resonance (CMR) combined with late gadolinium enhancement (LGE) has revealed a non-negligible increased incidence of myocardial fibrosis (MF) in athletes compared to healthy sedentary controls.Objective: The aim of this systematic research and meta-analysis is to investigate and present our perspective regarding CMR indices in athletes compared to sedentary controls, including T1 values, myocardial extracellular volume (ECV) and positive LGE indicative of non-specific fibrosis, also to discuss the differences between young and veteran athletes.Methods: The protocol included searching, up to October 2021, of MEDLINE, EMBASE, SPORTDiscus, Web of Science and Cochrane databases for original studies assessing fibrosis via CMR in athletes. A mean age of 40 years differentiated studies' athletic populations to veteran and young.Results: The research yielded 14 studies including in total 1,312 individuals. There was a statistically significant difference in LGE fibrosis between the 118/759 athletes and 16/553 controls (Z = 5.2, P &lt; 0.001, I2 = 0%, PI = 0.45). Notably, LGE fibrosis differed significantly between 546 (14.6%) veteran and 140 (25.7%) young athletes (P = 0.002). At 1.5T, T1 values differed between 117 athletes and 48 controls (P &lt; 0.0001). A statistically significant difference was also shown at 3T (110 athletes vs. 41 controls, P = 0.0004), as well as when pooling both 1.5T and 3T populations (P &lt; 0.00001). Mean ECV showed no statistically significant difference between these groups.Conclusions: Based on currently available data, we reported that overall LGE based non-specific fibrosis and T1 values differ between athletes and sedentary controls, in contrast to ECV values. Age of athletes seems to have impact on the incidence of MF. Future prospective studies should focus on the investigation of the underlying pathophysiological mechanisms.
DroughtCast: A Machine Learning Forecast of the United States Drought Monitor
Authors: Brust Colin , Kimball John S. , Maneta Marco P. , Jencso Kelsey , Reichle Rolf H. 
Published: December 2021

Drought is one of the most ecologically and economically devastating natural phenomena affecting the United States, causing the U.S. economy billions of dollars in damage, and driving widespread degradation of ecosystem health. Many drought indices are implemented to monitor the current extent and status of drought so stakeholders such as farmers and local governments can appropriately respond. Methods to forecast drought conditions weeks to months in advance are less common but would provide a more effective early warning system to enhance drought response, mitigation, and adaptation planning. To resolve this issue, we introduce DroughtCast, a machine learning framework for forecasting the United States Drought Monitor (USDM). DroughtCast operates on the knowledge that recent anomalies in hydrology and meteorology drive future changes in drought conditions. We use simulated meteorology and satellite observed soil moisture as inputs into a recurrent neural network to accurately forecast the USDM between 1 and 12 weeks into the future. Our analysis shows that precipitation, soil moisture, and temperature are the most important input variables when forecasting future drought conditions. Additionally, a case study of the 2017 Northern Plains Flash Drought shows that DroughtCast was able to forecast a very extreme drought event up to 12 weeks before its onset. Given the favorable forecasting skill of the model, DroughtCast may provide a promising tool for land managers and local governments in preparing for and mitigating the effects of drought.
FSHB Genotype Identified as a Relevant Diagnostic Parameter Revealed by Cluster Analysis of Men With Idiopathic Infertility
Authors: Krenz Henrike , Sansone Andrea , Kliesch Sabine , Gromoll Joerg , Schubert Maria 
Published: December 2021

Introduction and ObjectivesAbout 30-75% of infertile men are diagnosed with idiopathic infertility, thereby lacking major causative factors to explain their impaired fertility status. In this study, we used a large cohort of idiopathic infertile men to determine whether subgroups could be identified by an unbiased clustering approach and whether underlying etiologic factors could be delineated.Patients and MethodsFrom our in-house database Androbase®, we retrospectively selected patients (from 2008 to 2018) with idiopathic male infertility (azoo- to normozoospermia) who fit the following selection criteria: FSH ≥ 1 IU/l, testosterone ≥ 8 nmol/l, ejaculate volume ≥ 1.5 ml. Patients with genetic abnormalities or partners with female factors were excluded.For the identified study population (n=2742), we used common andrologic features (somatic, semen and hormonal parameters, including the FSHB c.-211G&gt;T (rs10835638) single nucleotide polymorphism) for subsequent analyses. Cluster analyses were performed for the entire study population and for two sub-cohorts, which were separated by total sperm count (TSC) thresholds: Cohort A (TSC ≥ 1 mill/ejac; n=2422) and Cohort B (TSC &lt; 1 mill/ejac; n=320). For clustering, the partitioning around medoids method was employed, and the quality was evaluated by average silhouette width.ResultsThe applied cluster approach for the whole study population yielded two separate clusters, which showed significantly different distributions in bi-testicular volume, FSH and FSHB genotype. Cluster 1 contained all men homozygous for G (wildtype) in FSHB c.-211G&gt;T (100%), while Cluster 2 contained most patients carrying a T allele (&gt;96.6%). In the analyses of sub-cohorts A/B, two clusters each were formed too. Again, the strongest segregation markers between the respective clusters were bi-testicular volume, FSH and FSHB c.-211G&gt;T.ConclusionWith this first unbiased approach for revealing putative subgroups within a heterogenous group of idiopathic infertile men, we did indeed identify distinct patient clusters. Surprisingly, across all diverse phenotypes of infertility, the strongest segregation markers were FSHB c.-211G&gt;T, FSH, and bi-testicular volume. Further, Cohorts A and B were significantly separated by FSHB genotype (wildtype vs. T-allele carriers), which supports the notion of a contributing genetic factor. Consequently, FSHB genotyping should be implemented as diagnostic routine in patients with idiopathic infertility.
Prenatal Diagnosis and Genetic Analysis of 21q21.1–q21.2 Aberrations in Seven Chinese Pedigrees
Authors: Hu Huamei , Zhang Rong , Ma Yongyi , Luo Yanmei , Pan Yan , Xu Juchun , Jiang Lupin , Wang Dan 
Published: December 2021

Background: Chromosomal aberrations contribute to human phenotypic diversity and disease susceptibility, but it is difficult to assess their pathogenic effects in the clinic. Therefore, it is of great value to report new cases of chromosomal aberrations associated with normal phenotypes or clinical abnormalities.Methods: This was a retrospective analysis of seven pedigrees that carried 21q21.1–q21.2 aberrations. G-banding and single-nucleotide polymorphism array techniques were used to analyze chromosomal karyotypes and copy number variations in the fetuses and their family members.Results: All fetuses and their family members showed normal karyotypes in seven pedigrees. Here, it was revealed that six fetuses carried maternally inherited 21q21.1–q21.2 duplications, ranging from 1 to 2.7 Mb, but none of the mothers had an abnormal phenotype. In one fetus, an 8.7 Mb deletion of 21q21.1–q21.2 was found. An analysis of the pedigree showed that the deletion was also observed in the mother, brother, and maternal grandmother, but no abnormal phenotypes were found.Conclusion: This study identified 21q21.1–q21.2 aberrations in Chinese pedigrees. The carriers of 21q21.1–q21.2 duplications had no clinical consequences based on their phenotypes, and the 21q21.1–q21.2 deletion was transmitted through three generations of normal individuals. This provides benign clinical evidence for pathogenic assessment of 21q21.1–q21.2 duplication and deletion, which was considered a variant of uncertain significance and a likely pathogenic variant in previous reports.
Sphingosine-1-Phosphate and Its Signal Modulators Alleviate Psoriasis-Like Dermatitis: Preclinical and Clinical Evidence and Possible Mechanisms
Authors: Liu Liu , Wang Jiao , Li Hong-jin , Zhang Shuo , Jin Meng-zhu , Chen Si-ting , Sun Xiao-ying , Zhou Ya-qiong , Lu Yi , Yang Dan , Luo Ying , Ru Yi , Li Bin , Li Xin 
Published: December 2021

BackgroundPsoriasis is an autoimmune skin disease associated with lipid metabolism. Sphingosine-1-phosphate (S1P) is a bioactive lipid that plays a key role in the development of autoimmune diseases. However, there is currently a lack of comprehensive evidence of the effectiveness of S1P on psoriasis.ObjectiveTo assess the efficacy and possible mechanism of S1P and its signal modulators in the treatment of psoriasis-like dermatitis.MethodsSix databases were searched through May 8, 2021, for studies reporting S1P and its signal modulators. Two reviewers independently extracted information from the enrolled studies. Methodological quality was assessed using SYRCLE’s risk of bias tool. RevMan 5.3 software was used to analyze the data. For clinical studies, the Psoriasis Area and Severity Index score were the main outcomes. For preclinical studies, we clarified the role of S1P and its regulators in psoriasis in terms of phenotype and mechanism.ResultsOne randomized double-blind placebo-controlled trial and nine animal studies were included in this study. The pooled results showed that compared with control treatment, S1P receptor agonists [mean difference (MD): −6.80; 95% confidence interval (CI): −8.23 to −5.38; p&lt;0.00001], and sphingosine kinase 2 inhibitors (MD: −0.95; 95% CI: −1.26 to −0.65; p&lt;0.00001) alleviated psoriasis-like dermatitis in mice. The mechanism of S1P receptor agonists in treating psoriasis might be related to a decrease in the number of white blood cells, topical lymph node weight, interleukin-23 mRNA levels, and percentage of CD3+ T cells (p&lt;0.05). Sphingosine kinase 2 inhibitors ameliorated psoriasis in mice, possibly by reducing spleen weight and cell numbers (p&lt;0.05).ConclusionsS1P receptor agonists and sphingosine kinase 2 inhibitors could be potential methods for treating psoriasis by decreasing immune responses and inflammatory factors.
Recombinant Human Proteoglycan 4 Regulates Phagocytic Activation of Monocytes and Reduces IL-1β Secretion by Urate Crystal Stimulated Gout PBMCs
Authors: ElSayed Sandy , Jay Gregory D. , Cabezas Ralph , Qadri Marwa , Schmidt Tannin A. , Elsaid Khaled A. 
Published: December 2021

ObjectivesTo compare phagocytic activities of monocytes in peripheral blood mononuclear cells (PBMCs) from acute gout patients and normal subjects, examine monosodium urate monohydrate (MSU) crystal-induced IL-1β secretion ± recombinant human proteoglycan 4 (rhPRG4) or interleukin-1 receptor antagonist (IL-1RA), and study the anti-inflammatory mechanism of rhPRG4 in MSU stimulated monocytes.MethodsAcute gout PBMCs were collected from patients in the Emergency Department and normal PBMCs were obtained from a commercial source. Monocytes in PBMCs were identified by flow cytometry. PBMCs were primed with Pam3CSK4 (1μg/mL) for 24h and phagocytic activation of monocytes was determined using fluorescently labeled latex beads. MSU (200μg/mL) stimulated IL-1β secretion was determined by ELISA. Reactive oxygen species (ROS) generation in monocytes was determined fluorometrically. PBMCs were incubated with IL-1RA (250ng/mL) or rhPRG4 (200μg/mL) and bead phagocytosis by monocytes was determined. THP-1 monocytes were treated with MSU crystals ± rhPRG4 and cellular levels of NLRP3 protein, pro-IL-1β, secreted IL-1β, and activities of caspase-1 and protein phosphatase-2A (PP2A) were quantified. The peritoneal influx of inflammatory and anti-inflammatory monocytes and neutrophils in Prg4 deficient mice was studied and the impact of rhPRG4 on immune cell trafficking was assessed.ResultsEnhanced phagocytic activation of gout monocytes under basal conditions (p&lt;0.001) was associated with ROS generation and MSU stimulated IL-1β secretion (p&lt;0.05). rhPRG4 reduced bead phagocytosis by normal and gout monocytes compared to IL-1RA and both treatments were efficacious in reducing IL-1β secretion (p&lt;0.05). rhPRG4 reduced pro-IL-1β content, caspase-1 activity, conversion of pro-IL-1β to mature IL-1β and restored PP2A activity in monocytes (p&lt;0.05). PP2A inhibition reversed rhPRG4’s effects on pro-IL-1β and mature IL-1β in MSU stimulated monocytes. Neutrophils accumulated in peritoneal cavities of Prg4 deficient mice (p&lt;0.01) and rhPRG4 treatment reduced neutrophil accumulation and enhanced anti-inflammatory monocyte influx (p&lt;0.05).ConclusionsMSU phagocytosis was higher in gout monocytes resulting in higher ROS and IL-1β secretion. rhPRG4 reduced monocyte phagocytic activation to a greater extent than IL-1RA and reduced IL-1β secretion. The anti-inflammatory activity of rhPRG4 in monocytes is partially mediated by PP2A, and in vivo, PRG4 plays a role in regulating the trafficking of immune cells into the site of a gout flare.
ERAP2 Is Associated With Immune Infiltration and Predicts Favorable Prognosis in SqCLC
Authors: Yang Zhenlin , Tian He , Bie Fenglong , Xu Jiachen , Zhou Zheng , Yang Junhui , Li Renda , Peng Yue , Bai Guangyu , Tian Yanhua , Chen Ying , Liu Lei , Fan Tao , Xiao Chu , Zheng Yujia , Zheng Bo , Wang Jie , Li Chunxiang , Gao Shugeng , He Jie 
Published: December 2021

BackgroundImmunotherapy has been proven effective among several human cancer types, including Squamous cell lung carcinoma (SqCLC). ERAP2 plays a pivotal role in peptide trimming of many immunological processes. However, the prognostic role of ERAP2 and its relationship with immune cell infiltration in SqCLC remains unclear.MethodsThe differential expression of ERAP2 was identified via GEO and TCGA databases. We calculated the impact of ERAP2 on clinical prognosis using the Kaplan-Meier plotter. TIMER was applied to evaluate the abundance of immune cells infiltration and immune markers. SqCLC tissue microarrays containing 190 patients were constructed, and we performed immunohistochemical staining for ERAP2, CD8, CD47, CD68, and PD-L1 to validate our findings in public data.ResultsIn the GEO SqCLC database, ERAP2 was upregulated in patients with better survival (p=0.001). ERAP2 expression in SqCLC was significantly lower than that of matched normal samples (p&lt;0.05) based on TCGA SqCLC data. Higher expression of ERAP2 was significantly associated with better survival in SqCLC patients from TCGA (p=0.007), KM-plotter (p=0.017), and our tissue microarrays (TMAs) (p=0.026). In univariate and multivariate Cox analysis of SqCLC TMAs, high ERAP2 expression was identified as an independent protective factor for SqCLC patients (Univariate Cox, HR=0.659, range 0.454-0.956, p&lt;0.05. Multivariate Cox, HR=0.578, range 0.385-0.866, p&lt;0.05). In TIMER, ERAP2 was positively correlated with several immune markers (CD274, p=1.27E-04; CD68, p=5.88E-08) and immune infiltrating cells (CD8+ T cell, p=4.09E-03; NK cell, p=1.00E-04). In our cohort, ERAP2 was significantly correlated with CD8+ tumor-infiltrating lymphocytes (TILs) (p=0.0029), and patients with higher ERAP2 expression had a higher percentage of PD-L1 positive patients (p=0.049) and a higher CD8+ TILs level (p=0.036).ConclusionsFor the first time, our study demonstrates that higher expression of ERAP2 is tightly associated with the immuno-supportive microenvironment and can predict a favorable prognosis in SqCLC. Meanwhile, ERAP2 may be a promising immunotherapeutic target for patients with SqCLC.
Comparison of Intraocular Cytokine Levels of Choroidal Neovascularization Secondary to Different Retinopathies
Authors: Liu Chenyi , Zhang Shian , Deng Xinyi , Chen Yijing , Shen Lijun , Hu Liang , Mao Jianbo 
Published: December 2021

Purpose: To investigate and compare the aqueous concentrations of vascular endothelial growth factor (VEGF) and other inflammatory cytokines in various choroidal neovascularization (CNV) diseases and types.Methods: This observational study included 127 naive eyes with CNV and 43 control eyes with cataracts. Aqueous humor (AH) samples were obtained prior to intravitreal anti-VEGF injection or cataract surgery. Multiple inflammatory cytokines, including VEGF, interleukin (IL) 6, IL-8, IL-10, interferon-inducible protein 10 (IP-10), and monocyte chemotactic protein 1 (MCP-1) levels, were measured using a multiplex bead assay. The angiogenesis index was defined as the ratio of IP-10 to MCP-1. In addition, the relationship among AH cytokine levels, central macular thickness (CMT), and CNV size on optical coherence tomography angiography (OCTA) was evaluated.Results: Except in the myopic CNV group (P = 0.452), the AH concentration of VEGF was significantly higher in all other CNV groups than in the control group (P &lt; 0.05 for all comparisons). IL-8, IL-10, IP-10, and MCP-1 levels (P &lt; 0.05 for all groups) were significantly higher in all CNV diseases except those with neovascular central serous chorioretinopathy. The angiogenesis index was significantly higher in all CNV diseases (P &lt; 0.05 for all comparisons). The VEGF level may be associated with the size of the CNV on OCTA (p = 0.043).Conclusions: The level of intraocular inflammatory cytokines varied among different CNV diseases and CNV types. Therefore, the angiogenesis index may be a more sensitive indicator of angiogenesis.
Dairy Product Consumption and Oligo-Astheno-Teratozoospermia Risk: A Hospital-Based Case-Control Study in China
Authors: Wang Xiao-Bin , Wu Qi-Jun , Guo Ren-Hao , Leng Xu , Du Qiang , Zhao Yu-Hong , Pan Bo-Chen 
Published: December 2021

Background: Researches on the association of dairy products consumption with Oligo-astheno-teratozoospermia (OAT) risk has been limited and controversial. Therefore, we aim to explore the aforementioned association among Chinese men.Methods: A hospital-based case-control study was conducted in men consisting of 106 cases of OAT and 581 controls. Intakes of dairy products and their related nutrients were collected using a semi-quantitative food frequency questionnaire and semen quality was analyzed according to the World Health Organization guidelines. The daily intake of dairy products and their related nutrients was categorized into three groups with the lowest tertile serving as the reference category. Odds ratios (ORs) and 95% confidence intervals (CIs) of association between dairy intake and OTA risk were calculated by the multivariable logistic regression models.Results: No significant association was found between total dairy (OR T3vs.T1 =1.53, 95% CI: 0.85–2.78), protein (OR T3vs.T1 =1.51, 95% CI: 0.84–2.75), or calcium (OR T3vs.T1 = 1.46, 95% CI: 0.81–2.66) and the OAT risk in the main findings. However, we observed a statistically significant positive association of dairy fat intake with OAT risk (OR T3vs.T1 =1.93, 95% CI: 1.06–3.58). The findings were consistent with the main results when we carried out subgroup analysis stratified by body mass index.Conclusion: A significant positive association was found between dairy fat intake and the risk of OAT. Further large-scale prospective studies are required to confirm this finding.
Prognostic Factors of Colorectal Cancer: A Comparative Study on Patients With or Without Liver Metastasis
Authors: Peng Honghua , Liu Guifeng , Bao Ying , Zhang Xi , Zhou Lehong , Huang Chenghui , Song Zewen , Cao Sudan , Dang Shiying , Zhang Jing , Huang Tanxiao , Wu Yuling , Xu Mingyan , Song Lele , Cao Peiguo 
Published: December 2021

BackgroundRadical or palliative surgery with subsequent adjuvant therapy is the routine treatment for stage II/III colorectal cancer(CRC) and some stage IV CRC patients. This study aimed to clarify the prognostic clinicopathological and genetic factors for these patients.MethodsFifty-five stage II-IV CRC patients undergoing surgery and adjuvant therapy were recruited, including patients without liver metastasis(5 at stage II, 21 at stage III) and with liver metastasis(29 at stage IV). Genetic alterations of the primary cancer tissues were investigated by whole exome sequencing(WES). Patients were followed up to 1652 days(median at 788 days).ResultsThe mutational landscape of primary CRC tissue of patients with or without liver metastasis was largely similar, although the mutational frequency of TRIM77 and TCF7L2 was significantly higher in patients with liver metastasis. Several main driver gene co-mutations, such as TP53-APC, APC-KRAS, APC-FRG1, and exclusive mutations, such as TP53-CREBBP, were found in patients with liver metastasis, but not in patients without liver metastasis. No significant difference was found between the two groups in aberrant pathways. If stage II-IV patients were studied altogether, relapse status, SUPT20HL1 mutations, Amp27_21q22.3 and Del8_10q23.2 were independent risk factors(P&lt;0.05). If patients were divided into two groups by metastatic status, surgery types and Amp6_20q13.33 were independent risk factors for patients without liver metastasis(P&lt;0.05), while TRIM77 mutations were the only independent risk factor for patients with liver metastasis(P&lt;0.05).ConclusionsSurgery types and Amp6_20q13.33 were independent risk factors for CRC patients without liver metastasis, and TRIM77 mutations were the independent risk factor for CRC patients with liver metastasis.