bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictive Value of Immune Cells in the Risk of Gestational Diabetes Mellitus: A Pilot Study
Authors: Fagninou Adnette , Nekoua Magloire Pandoua , Fiogbe Salomon Ezéchiel M. , Moutaïrou Kabirou , Yessoufou Akadiri
Published: February 2022

Aims

Immunological and biochemical parameters are gaining more and more importance in the prognosis of diabetes and its complications. Here, we assessed the predictive power of immune cells correlated with biochemical parameters in gestational diabetes mellitus (GDM).

Materials and Methods

Immune cells and serum biochemical parameters were determined in women with GDM and pregnant controls. Receiver operating characteristics (ROC) curve analyses were conducted to assess the optimal cutoff and value of ratios of immune cells to biochemical parameters for predicting GDM.

Results

Blood glucose, total cholesterol, LDL-cholesterol and triglycerides were significantly increased whereas HDL-cholesterol decreased in women with GDM compared to pregnant controls. Glycated hemoglobin, creatinine, transaminase activities did not significantly differ between both groups. Total leukocyte, lymphocyte and platelet numbers were significantly high in women with GDM. Correlation tests showed that ratios of lymphocyte/HDL-C, monocyte/HDL-C and granulocyte/HDL-C were significantly higher in women with GDM than in pregnant controls (p = 0.001; p = 0.009 and p = 0.004 respectively). Women with a lymphocyte/HDL-C ratio greater than 3.66 had a 4-fold increased risk of developing GDM than those with lower ratios (odds ratio 4.00; 95% CI: 1.094 – 14.630; p=0.041).

Conclusion

Our study showed that ratios of lymphocyte, monocyte and granulocyte to HDL-C might represent valuable biomarkers for GDM and in particular, lymphocyte/HDL-C ratio exhibited a strong predictive power for GDM risk.
A Bibliometric Analysis Based on Web of Science: Current Perspectives and Potential Trends of SMAD7 in Oncology
Authors: Huang Xueying , Yang Zhiying , Zhang Jinning , Wang Ruojiao , Fan Jiahui , Zhang Heng , Xu Rong , Li Xia , Yu Siying , Long Linna , Huang He
Published: February 2022

Background: The number of publications on SMAD7 in the field of oncology is increasing rapidly with an upward tendency. In most cases, the mechanisms of carcinogenesis usually relate to disorders of signaling activity. Considering the crucial role of SMAD7 in the crosstalk of multiple signaling pathways, it is necessary to clarify and define the dominant research topics, core authors, and their cumulative research contributions, as well as the cooperative relationships among documents or researchers.

Methods: Altogether, 3477 documents were retrieved from the Web of Science Core Collection with the following criteria: TS= (SMAD7 OR SMAD7-protein OR Small-Mothers-Against-Decapentaplegic-7) refined by WEB OF SCIENCE CATEGORY (ONCOLOGY) AND [excluding] PUBLICATION YEARS (2021) AND DOCUMENT TYPES (ARTICLE OR REVIEW) AND LANGUAGES (ENGLISH) AND WEB OF SCIENCE INDEX (Web of Science Core Collection, SCI), and the timespan of 2011–2020. Bibliometric visualization analysis was conducted with CiteSpace and VOSviewer.

Results: The number of documents grew each year. A total of 2703 articles and 774 reviews were identified from 86 countries/regions, 3524 organizations, 928 journals, and 19,745 authors. China was the most prolific country, with 1881 documents. Contributions from China, the United States, and Germany were the most substantial. The most influential author was Lan Huiyao at The Chinese University of Hong Kong, with 24 publications and 2348 total citations. The bibliometric analysis showed that multilateral cooperation among diverse institutions or investigators was beneficial to high-quality outputs. The keyword “PPAR-gamma” exhibited the strongest burst in recent years, suggesting a potent research focus in the future.

Conclusion: Research on SMAD7 in oncology is continuously developing. Bibliometrics is an interesting tool to present the characteristics of publication years, main authors, and productive organizations in a visualized way. It is worth mentioning that a prospective focus might be the specific mechanism of the interaction of PPAR-gamma with SMAD7 in oncology. In all, bibliometric analysis provides an overview and identifies potential research trends for further studies in this academic field.
Deciphering Cell-Type-Specific Gene Expression Signatures of Cardiac Diseases Through Reconstruction of Bulk Transcriptomes
Authors: Wu Xiaobin , Zhao Xingyu , Xiong Yufei , Zheng Ming , Zhong Chao , Zhou Yuan
Published: February 2022

Cardiac diseases compose a fatal disease category worldwide. Over the past decade, high-throughput transcriptome sequencing of bulk heart tissues has widened our understanding of the onset and progression of cardiac diseases. The recent rise of single-cell RNA sequencing (scRNA-seq) technology further enables deep explorations of their molecular mechanisms in a cell-type-specific manner. However, due to technical difficulties in performing scRNA-seq on heart tissues, there are still few scRNA-seq studies on cardiac diseases. In this study, we demonstrate that an effective alternative could be cell-type-specific computational reconstruction of bulk transcriptomes. An integrative bulk transcriptome dataset covering 110 samples from 12 studies was first constructed by re-analysis of raw sequencing data derived from the heart tissues of four common cardiac disease mouse models (myocardial infarction, dilated cardiomyopathy, hypertrophic cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy). Based on the single-cell reference covering four major cardiac component cell types and 22 immune cell subtypes, for each sample, the bulk transcriptome was reconstructed into cellular compositions and cell-type-specific expression profiles by CIBERSORTx. Variations in the estimated cell composition revealed elevated abundances of fibroblast and monocyte during myocardial infarction, which were further verified by our flow cytometry experiment. Moreover, through cell-type-specific differential gene expression and pathway enrichment analysis, we observed a series of signaling pathways that mapped to specific cell type in diseases, like MAPK and EGFR1 signaling pathways in fibroblasts in myocardial infarction. We also found an increased expression of several secretory proteins in monocytes which may serve as regulatory factors in cardiac fibrosis. Finally, a ligand–receptor analysis identified key cell types which may serve as hubs in cellular communication in cardiac diseases. Our results provide novel clues for the cell-type-specific signatures of cardiac diseases that would promote better understanding of their pathophysiological mechanisms.
Development and Validation of a Novel Histone Acetylation-Related Gene Signature for Predicting the Prognosis of Ovarian Cancer
Authors: Dai Qinjin , Ye Ying
Published: February 2022

Histone acetylation is one of the most common epigenetic modifications, which plays an important role in tumorigenesis. However, the prognostic role of histone acetylation-regulators in ovarian cancer (OC) remains little known. We compared the expression levels of 40 histone acetylation-related genes between 379 OC samples and 88 normal ovarian tissues and identified 37 differently expressed genes (DEGs). We further explored the prognostic roles of these DEGs, and 8 genes were found to be correlated with overall survival (p < 0.1). In the training stage, an 8 gene‐based signature was conducted by the least absolute shrinkage and selector operator (LASSO) Cox regression. Patients in the training cohort were divided into two risk subgroups according to the risk score calculated by the 8-gene signature, and a notable difference of OS was found between the two subgroups (p < 0.001). The 8-gene risk model was then verified to have a well predictive role on OS in the external validation cohort. Combined with the clinical characteristics, the risk score was proved to be an independent risk factor for OS. In conclusion, the histone acetylation-based gene signature has a well predictive effect on the prognosis of OC and can potentially be applied for clinical treatments.
Therapeutic Effects of Kefir Peptides on Hemophilia-Induced Osteoporosis in Mice With Deficient Coagulation Factor VIII
Authors: Yen Chih-Ching , Liu Yao-Wen , Chang Gary Ro-Lin , Lan Ying-Wei , Kao Yung-Tsung , Cheng Shin-Nan , Chen Wei , Chen Chuan-Mu
Published: February 2022

Osteoporosis is a clinically prevalent comorbidity in patients with hemophilia. A preventive effect of kefir peptides (KPs) on postmenopausal osteoporosis has been proved. The aim of this study was to evaluate the therapeutic effect of KPs for the treatment of osteoporosis in coagulation factor VIII (FVIII) gene knockout mice (F8KO), a model of hemophilia A. In this study, male F8KO mice at 20 weeks of age were orally administered different doses of KPs for 8 weeks. The therapeutic effects of KPs were shown in the femoral trabeculae and the 4thlumbar vertebrae, which increased the trabecular bone mineral density (BMD), bone volume (Tb.BV/TV), and trabecular number (Tb.N) and decreased the trabecular separation (Tb.Sp), and they were also observed in the femoral cortical bones, in which the mechanical properties were enhanced in a dose-dependent manner. Characterization of receptor activator of nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), and interleukin 6 (IL-6) demonstrated that the serum RANKL/OPG ratio and IL-6 levels were significantly decreased in the F8KO mice after the KP treatment. Tartrate-resistant acid phosphatase (TRAP) staining of mature osteoclasts indicated that the therapeutic effect of KPs in F8KO mice was associated with the functions of KPs to inhibit RANKL-induced osteoclastogenesis by reducing serum RANKL/OPG ratio and IL-6 secretion. The present study is the first to address the potentials of KPs for the treatment of hemophilia-induced osteoporosis in mice and it also provides useful information for the application of KPs as a complementary therapy for the treatment of osteoporosis in hemophilic patients.
Single-Cell Transcriptome Reveals the Metabolic and Clinical Features of a Highly Malignant Cell Subpopulation in Pancreatic Ductal Adenocarcinoma
Authors: Fang Yangyang , Pei Shunjie , Huang Kaizhao , Xu Feng , Xiang Guangxin , Lan Linhua , Zheng Xiaoqun
Published: February 2022

Background: Pancreatic ductal adenocarcinoma (PDAC) is a malignant tumor with a high mortality rate. PDAC exhibits significant heterogeneity as well as alterations in metabolic pathways that are associated with its malignant progression. In this study, we explored the metabolic and clinical features of a highly malignant subgroup of PDAC based on single-cell transcriptome technology.

Methods: A highly malignant cell subpopulation was identified at single-cell resolution based on the expression of malignant genes. The metabolic landscape of different cell types was analyzed based on metabolic pathway gene sets. In vitro experiments to verify the biological functions of the marker genes were performed. PDAC patient subgroups with highly malignant cell subpopulations were distinguished according to five glycolytic marker genes. Five glycolytic highly malignant-related gene signatures were used to construct the glycolytic highly malignant-related genes signature (GHS) scores.

Results: This study identified a highly malignant tumor cell subpopulation from the single-cell RNA sequencing (scRNA-seq) data. The analysis of the metabolic pathway revealed that highly malignant cells had an abnormally active metabolism, and enhanced glycolysis was a major metabolic feature. Five glycolytic marker genes that accounted for the highly malignant cell subpopulations were identified, namely, EN O 1, LDHA, PKM, PGK1, and PGM1. An in vitro cell experiment showed that proliferation rates of PANC-1 and CFPAC-1 cell lines decreased after knockdown of these five genes. Patients with metabolic profiles of highly malignant cell subpopulations exhibit clinical features of higher mortality, higher mutational burden, and immune deserts. The GHS score evaluated using the five marker genes was an independent prognostic factor for patients with PDAC.

Conclusion: We revealed a subpopulation of highly malignant cells in PDAC with enhanced glycolysis as the main metabolic feature. We obtained five glycolytic marker gene signatures, which could be used to identify PDAC patient subgroups with highly malignant cell subpopulations, and proposed a GHS prognostic score.
Function of Proneural Genes Ascl1 and Asense in Neurogenesis: How Similar Are They?
Authors: Soares Diogo S. , Homem Catarina C.F. , Castro Diogo S.
Published: February 2022

Proneural genes were initially identified in Drosophila, where pioneer work on these important regulators of neural development was performed, and from which the term proneural function was coined. Subsequently, their counterparts in vertebrates were identified, and their function in neural development extensively characterized. The function of proneural transcription factors in flies and vertebrates is, however, very distinct. In flies, proneural genes play an early role in neural induction, by endowing neural competence to ectodermal cells. In contrast, vertebrate proneural genes are expressed only after neural specification, in neural stem and progenitor cells, where they play key regulatory functions in quiescence, proliferation, and neuronal differentiation. An exception to this scenario is the Drosophila proneural gene asense, which has a late onset of expression in neural stem cells of the developing embryo and larvae, similar to its vertebrate counterparts. Although the role of Asense remains poorly investigated, its expression pattern is suggestive of functions more in line with those of vertebrate proneural genes. Here, we revise our current understanding of the multiple activities of Asense and of its closest vertebrate homologue Ascl1 in neural stem/progenitor cell biology, and discuss possible parallels between the two transcription factors in neurogenesis regulation.
Uncover New Reactivity of Genetically Encoded Alkyl Bromide Non-Canonical Amino Acids
Authors: Shu Xin , Asghar Sana , Yang Fan , Li Shang-Tong , Wu Haifan , Yang Bing
Published: February 2022

Genetically encoded non-canonical amino acids (ncAAs) with electrophilic moieties are excellent tools to investigate protein-protein interactions (PPIs) both in vitro and in vivo. These ncAAs, including a series of alkyl bromide-based ncAAs, mainly target cysteine residues to form protein-protein cross-links. Although some reactivities towards lysine and tyrosine residues have been reported, a comprehensive understanding of their reactivity towards a broad range of nucleophilic amino acids is lacking. Here we used a recently developed OpenUaa search engine to perform an in-depth analysis of mass spec data generated for Thioredoxin and its direct binding proteins cross-linked with an alkyl bromide-based ncAA, BprY. The analysis showed that, besides cysteine residues, BprY also targeted a broad range of nucleophilic amino acids. We validated this broad reactivity of BprY with Affibody/Z protein complex. We then successfully applied BprY to map a binding interface between SUMO2 and SUMO-interacting motifs (SIMs). BprY was further applied to probe SUMO2 interaction partners. We identified 264 SUMO2 binders, including several validated SUMO2 binders and many new binders. Our data demonstrated that BprY can be effectively used to probe protein-protein interaction interfaces even without cysteine residues, which will greatly expand the power of BprY in studying PPIs.
Molecular Characteristics of Regional Chromoblastomycosis in Guangdong, China: Epidemiological, Clinical, Antifungal Susceptibility, and Serum Cytokine Profiles of 45 Cases
Authors: Liu Hongfang , Sun Jiufeng , Li Minying , Cai Wenying , Chen Yangxia , Liu Yinghui , Huang Huan , Xie Zhenmou , Zeng Weiying , Xi Liyan
Published: February 2022

Chromoblastomycosis (CBM) is a chronic disease caused by several species of dematiaceous fungi. In this study, a regional collection of 45 CBM cases was conducted in Guangdong, China, a hyper-endemic area of CBM. Epidemiology findings indicated that the mean age of cases was 61.38 ± 11.20 years, long duration ranged from 3 months to 30 years, and the gender ratio of male to female was 4.6:1. Thirteen cases (29%) declared underlying diseases. Verrucous form was the most common clinical manifestation (n = 19, 42%). Forty-five corresponding clinical strains were isolated, and 28 of them (62%) were identified as F. monophora; the remaining 17 (38%) were identified as F. nubica through ITS rDNA sequence analysis. Antifungal susceptibility tests in vitro showed low MICs in azoles (PCZ 0.015–0.25 μg/ml, VCZ 0.015–0.5 μg/ml, and ITZ 0.03–0.5 μg/ml) and TRB (0.015–1 μg/ml). Itraconazole combined with terbinafine was the main therapeutic strategy used for 31 of 45 cases, and 68% (n = 21) of them improved or were cured. Cytokine profile assays indicated upregulation of IL-4, IL-7, IL-15, IL-11, and IL-17, while downregulation of IL-1RA, MIP-1β, IL-8, and IL-16 compared to healthy donors (p < 0.05). The abnormal cytokine profiles indicated impaired immune response to eliminate fungus in CBM cases, which probably contributed to the chronic duration of this disease. In conclusion, we investigated the molecular epidemiological, clinical, and laboratory characteristics of CBM in Guangdong, China, which may assist further clinical therapy, as well as fundamental pathogenesis studies of CBM.
Future Changes of Summer Heat Waves Over Urban Agglomerations in Eastern China Under 1.5°C and 2.0°C Global Warming
Authors: Ma Hongyun , Wang Ying , Lin Zhaohui
Published: February 2022

Extreme hot events have increased evidently under global warming, particularly in the urban areas. This study aims to explore the detailed features of future changes in summer heat waves (HWs) over three major urban agglomerations (Beijing Tianjin Hebei, BTH; Yangtze River Delta, YRD; Pearl River Delta, PRD) in eastern China under 1.5 and 2.0°C warming scenario by using the Weather Research and Forecasting model (WRF) with the updated land cover data for China (ChinaLC), which is also coupled with urban canopy model. Based on the future projection results from Community Earth System Model (CESM) under the Representative Concentration Pathway (RCP) 4.5, dynamic downscaling with high-resolution WRF has been performed to project the future changes in frequency, duration and intensity of summer HWs in urban agglomerations under 1.5 and 2.0°C warming scenarios respectively. Compared with the historical period, it is found that both the summer HWs indices and the HWs affected areas all increase significantly under 1.5 and 2.0°C warming scenarios. The increasing rates of the three HWs indices are above 50% under 1.5°C warming situation, and 70% for 2.0°C warming scenario, with the increasing rate of HWs intensity even exceeding 200%. It is noted that an additional 0.5°C warming from 1.5 to 2.0°C can produce much larger impact on the future HWs changes in YRD, with the HWs intensity increased by 75.5% from 1.5 to 2.0°C warming scenarios. It is further found that the changes of HWs indices in urban area is much higher than that of non-urban areas under 1.5 and 2.0°C warming, indicating that the urban areas will face higher risk of heat-related illness or environments than suburban or rural areas in the future. Our results can provide further scientific support for the mitigation and adaption strategy for the future HWs risk in mega-cities.
The Influence Mechanism of Pore Structure of Tectonically Deformed Coal on the Adsorption and Desorption Hysteresis
Authors: Ren Jiangang , Weng Hongbo , Li Bing , Chen Feng , Liu Jianbao , Song Zhimin
Published: February 2022

Pore is the main adsorption and desorption space of coalbed methane (CBM). Pore size configuration and connectivity affect the adsorption/desorption hysteresis effect. Using tectonically deformed coal (TDC) and original structure coal of medium- and high-rank coal as the research objects, through the N2/CO2 adsorption experiment to analyze the pore size distribution and connectivity of different scales. We investigate the control mechanism of heterogeneous evolution in the key pore scales against adsorption/desorption hysteresis characteristics during coal metamorphism and deformation by combining the CH4 isothermal adsorption/desorption experiment under 30°C equilibrium moisture. The findings indicate that the super micropores (<2 nm) are mainly combination ink bottle-shaped pores and have worse connectivity as the degree of metamorphism and deformation increases. The super micropores occupy the vast majority of pore volume and specific surface area; its pore size distribution curve change presents an “M” bimodal type and is mainly concentrated in two pore segments of 0.45–0.70 nm and 0.70–0.90 nm. The effect of ductile deformation exerts a significantly greater effect on super micropores than brittle deformation. The exhibited adsorption–desorption characteristics are the result of the combined effect of the unique pore structure of the TDCs and different moisture contents. The presence of a large number of super micropores is the most important factor influencing the degree of gas desorption hysteresis. The “ink-bottle effect” is the primary cause of gas desorption hysteresis. For CBM development, some novel methods to increase desorption and diffusion rate at the super micropores scale should be considered.
Pressure Calibration of Large-Volume Press: A Case Study of Hinged 6-8 Type Large-Volume High-Pressure Apparatus
Authors: Ren Dongsheng , Li Heping
Published: February 2022

In this study, methods for the pressure calibration of 6–8 static high-pressure apparatus were investigated. The relationship between the pressure of DS 6 × 1,400 t pressing oil and the chamber pressure was calibrated using water, ZnTe, ZnS, and GaAs at room temperature. Also, the relationship between the pressure of the DS 6 × 1,400 t pressing oil and the chamber pressure was calibrated by the phase transition experiments using KCl, LiCl, KCl + LiCl, and quartz-coesite at high temperatures. We found a linear relationship between the chamber pressure and the oil pressure at room temperature. However, when the temperature and pressure increased to certain values, the chamber pressure and the oil pressure deviated from the linear relationship.
Embedded System Design Student’s Learning Readiness Instruments: Systematic Literature Review
Authors: Elfadil Nazar , Ibrahim Intisar
Published: February 2022

To evaluate and measure the effects of student’s preparation before studying an embedded system design course, a systematic literature analysis was conducted, spanning publications from 1992 to 2020. Furthermore, evaluating such effects may help to close the gap between academically taught abilities and industry-required skills. The goal of the review was to gather and evaluate all reputable and effective studies that have looked into students’ learning preparation issues and solutions in embedded system design courses. Nonetheless, the purpose of this work was to extract and discuss the key features and methodologies from the selected research publications in order to present researchers and practitioners with a clear set of recommendations and solutions. The findings revealed that no instrument has been developed yet to assess students’ readiness to take up an embedded system design course. Furthermore, the majority of the instruments offered lacked concept clarity.
IL-15 Participates in the Pathogenesis of Polycystic Ovary Syndrome by Affecting the Activity of Granulosa Cells
Authors: Liu Yan , Li Zhi , Wang Yang , Cai Qingqing , Liu Haiou , Xu Congjian , Zhang Feifei
Published: February 2022

Background

Low-grade chronic inflammation may contribute to the pathogenesis of polycystic ovary syndrome (PCOS). Interleukin-15 (IL-15) is a proinflammatory cytokine involved in the development of chronic inflammation leading to obesity-associated metabolic syndrome. However, the concentration of IL-15 in follicular fluid of patients with PCOS has yet been evaluated.

Objectives

The aim of this study is to evaluate the expression level of IL-15 in both patients with PCOS and PCOS mice model and investigate the functional effect of IL-15 on ovarian granulosa cells.

Methods

The level of IL-15 in follicular fluid (FF) was measured using cytokine array and enzyme linked immunosorbent assay (ELISA) in two cohorts from 23 PCOS patients and 18 normo-ovulatory controls. PCOS mice model was induced by subcutaneously implanted with letrozole pellet for 21 days. The expression level of IL-15 in serum, ovarian, and subcutaneous adipose tissue in PCOS mice model was measured by ELISA, real-time polymerase chain reaction (RT-PCR), immunohistochemistry (IHC), and immunofluorescence. The effect of IL-15 on the proliferation and apoptosis of the KGN cells and mouse ovarian granulosa cells (GCs) were detected by CCK-8 assay and flow cytometry, respectively. Transcript expression of 17α-hydroxylase17,20-lyase (CYP17A1), cytochrome P450 family 19 subfamily A member 1(CYP19A1), FSH receptor (FSHR), steroidogenic acute regulatory protein (StAR), and proinflammatory cytokine were quantified using RT-PCR. The protein level and phosphorylation level of p38 MAPK and JNK are detected by Western blot. Concentration of dehydroepiandrosterone sulfate (DHEAS) and progesterone (P)were measured by ELISA.

Results

IL-15 expression in follicular fluid of patients with PCOS was significantly elevated compared with the control group, and similar results were observed in the ovarian and subcutaneous adipose tissue of PCOS mice models. Furthermore, the elevated FF IL-15 levels have a positive correlation with the serum testosterone levels. FSHR co-localized with IL-15 indicating that IL-15 production originate from ovarian granulose cells. IL-15 treatment inhibited proliferation and promoted apoptosis of KGN cells and mouse GCs. Moreover, IL-15 upregulated the transcription levels of CYP17A1, IL-1b and Ifng KGN cells. Similar results were observed in mouse GCs except concentration of DHEAS was higher in IL-15 treatment. IL-15 promoted p38 MAPK and JNK phosphorylation in KGN cells, treating KGN cells with p38 MAPK inhibitor SP600125 and JNK inhibitor SB203580 could reverse the effect of IL-15 on the proliferation and function of KGN cells.

Conclusion

The results indicate that IL-15 is involved in the pathogenesis of PCOS potentially by affecting survival, the inflammation state and steroidogenesis of granulosa cells. The practical significance of this association between IL-15 and the pathogenesis of PCOS needs further investigation.
Pubertal Timing and Growth Dynamics in Children With Severe Primary IGF-1 Deficiency: Results From the European Increlex® Growth Forum Database Registry
Authors: Bang Peter , Polak Michel , Perrot Valérie , Sert Caroline , Shaikh Haris , Woelfle Joachim
Published: February 2022

Background

Puberty is delayed in untreated children and adolescents with severe primary IGF-1 deficiency (SPIGFD); to date, it has not been reported whether recombinant human insulin-like growth factor-1 mecasermin (rhIGF-1) treatment affects this. Pubertal growth outcomes were extracted from the European Increlex® Growth Forum Database (Eu-IGFD) Registry (NCT00903110).

Methods

The Eu-IGFD Registry includes children and adolescents aged 2 to 18 years with growth failure associated with SPIGFD who are treated with rhIGF-1. Reported outcomes include: age at last registration of Tanner stage 1 and first registration of Tanner stage 2-5 (T2-T5; based on breast development for girls and genital development for boys, respectively); maximum height velocity during each Tanner stage; and pubertal peak height velocity (PPHV). Data cut-off was 13 May 2019.

Results

This analysis included 213 patients (132 boys and 81 girls). Mean (SD) age at last registration of T1 and first registration of T5 was 13.0 (2.0) and 16.3 (1.6) years, respectively, in boys and 11.6 (1.8) and 14.7 (1.5) years, respectively, in girls. Among patients reaching the end of puberty (25 boys and 11 girls), mean (SD) height SDS increased from -3.7 (1.4) at baseline in the Eu-IGFD Registry to -2.6 (1.4) at T5 in boys and from -3.1 (1.1) to -2.3 (1.5) in girls. Maximum height velocity was observed during T2 in girls and T3 in boys. Median (range) PPHV was 8.0 (0.3–13.0) cm/year in boys and 6.8 (1.3–9.6) cm/year in girls and occurred most frequently during T2. Overall, the adverse events seen in this analysis were in line with the known safety profile of rhIGF-1.

Conclusion

Children and adolescents treated with rhIGF-1 for SPIGFD with growth failure experienced an increase in height SDS in prepubertal years compared with baseline. Despite 1.5 years delay in pubertal start and a delayed and slightly lower PPHV, height SDS gain during puberty was maintained.
Evidence From a Systematic Review and Meta-Analysis: Classical Impaired Glucose Tolerance Should Be Divided Into Subgroups of Isolated Impaired Glucose Tolerance and Impaired Glucose Tolerance Combined With Impaired Fasting Glucose, According to the Risk of Progression to Diabetes
Authors: Liu Yupu , Li Juan , Wu Yuchao , Zhang Han , Lv Qingguo , Zhang Yuwei , Zheng Xiaofeng , Tong Nanwei
Published: February 2022

Background

The American Diabetes Association (ADA) 2003 diagnostic criteria divide impaired glucose tolerance (IGT) into isolated impaired glucose tolerance with normal fasting glucose (I-IGT, IGT+NFG) and impaired glucose tolerance combined with impaired fasting glucose (IGT+IFG), while the World Health Organization (WHO) 1999 criteria do not. The aim of this meta-analysis was to evaluate whether IGT should be divided into I-IGT (IGT+NFG) or IGT+IFG according to their risk of progression to type 2 diabetes.

Methods

The MEDLINE and EMBASE were searched to identify prospective cohort studies published in English prior to April 18, 2020. Review Manager 5.3 was used to calculate the pooled risk ratios (RRs) and 95% confidence intervals (CIs) as summary statistics for each included study.

Results

Sixteen eligible studies (n = 147,006) were included in the analysis. The subsequent incidence of type 2 diabetes was lower in the I-IGT (IGT+NFG) group than in the IGT+IFG group (0.45 [95% CI 0.37, 0.55] according to WHO 1999 criteria and 0.59 [95% CI 0.54, 0.66] according to ADA 2003 criteria). It was higher in the I-IFG, I-IGT (IGT+NFG), and IGT+IFG groups than in the normoglycemic group (95% CI of 5.53 [3.78, 8.08], 5.21 [3.70, 7.34], and 11.87 [7.33, 19.20] according to the WHO 1999 criteria and 95% CI of 2.66 [2.00, 3.54], 3.34 [2.81, 3.97], and 6.10 [4.72, 7.88] according to the ADA 2003 criteria). In general, the incidence of diabetes in the IGT+IFG group was the highest in the prediabetic population.

Conclusions

The present meta-analysis suggested that the established WHO diagnostic criteria for IGT should be revised to separately identify individuals with IGT+NFG or IGT+IFG.
Organokines and Exosomes: Integrators of Adipose Tissue Macrophage Polarization and Recruitment in Obesity
Authors: Wang Yuan-Yuan , Wang Ya-Di , Qi Xiao-Yan , Liao Zhe-Zhen , Mai Yun-Ni , Xiao Xin-Hua
Published: February 2022

The prevalence of obesity is escalating and has become a worldwide health challenge coinciding with the development of metabolic diseases. Emerging evidence has shown that obesity is accompanied by the infiltration of macrophages into adipose tissue, contributing to a state of low-grade chronic inflammation and dysregulated metabolism. Moreover, in the state of obesity, the phenotype of adipose tissue macrophages switches from the M2 polarized state to the M1 state, thereby contributing to chronic inflammation. Notably, multiple metabolic organs (adipose tissue, gut, skeletal muscle, and the liver) communicate with adipose tissue macrophages via secreting organokines or exosomes. In this review, we systematically summarize how the organokines (adipokines, gut microbiota and its metabolites, gut cytokines, myokines, and hepatokines) and exosomes (adipocyte-, skeletal muscle-, and hepatocyte-derived exosomes) act as important triggers for macrophage recruitment in adipose tissue and adipose tissue macrophage polarization, thus providing further insight into obesity treatment. In addition, we also highlight the complex interaction of organokines with organokines and organokines with exosomes, revealing new paths in understanding adipose tissue macrophage recruitment and polarization.
Experimental Analysis of Heat Storage and Release of Binary Methanol Aqueous Solution Pulsating Heat Pipe Phase Change Accumulator
Authors: Lu Xiaohui , Luo Xiaoxue , Cao Shibo , Zou Changzhen
Published: February 2022

To improve the problems of energy shortage and low utilization rate, this paper designed a set of pulsating heat pipe (PHP) devices coupled with phase change energy storage material. Further, the binary methanol-water solution is proposed as a novel experimental filling medium to enhance the heat transfer performance of the device. The fluid flow model of the PHP was analyzed via experiment and simulation. Besides, the heat storage and release performances of the PHP at different flow rates, different heating temperatures, different filling mediums, and different filling ratios are investigated. The results show that when the filling medium (binary methanol-water solution) possesses the filling ratio of 0.6 (methanol and water are each 0.3), the heat source inlet flow is 0.60 m3/h, the heat source heating temperature is 120°C, and the PHP is at the best heat storage performance. During the exothermic process, the lower the initial temperature of cooling water, the higher the heat recovery rate. Thus, it can be concluded that the selection of an appropriate filling medium and the optimal parameters to enhance heat transfer can have a broader application prospect in the field of waste heat recovery.
Do Electric Vehicles Mitigate Urban Heat? The Case of a Tropical City
Authors: Mussetti Gianluca , Davin Edouard L. , Schwaab Jonas , Acero Juan A. , Ivanchev Jordan , Singh Vivek Kumar , Jin Luxi , Seneviratne Sonia I.
Published: February 2022

On top of their well known positive impact on air quality and CO2 emissions, electric vehicles generate less exhaust heat compared to traditional vehicles thanks to their high engine efficiency. As such, electric vehicles have the potential to mitigate the excessive heat in urban areas—a problem which has been exacerbated due to urbanisation and climate change. Still, the heat mitigation potential of electric vehicles has not been fully understood. Here, we combine high-resolution traffic heat emission inventories with an urban climate model to simulate the impact of the fleet electrification to the near-surface air temperature in the tropical city of Singapore. We show that a full replacement of traditional internal combustion engine vehicles with electric vehicles reduces the near-surface air temperature by up to 0.6°C. The heat mitigation potential is highest during the morning traffic peak and over areas with the largest traffic density. Interestingly, the reduction in exhaust heat emissions due to the fleet electrification during the evening traffic peak hardly leads to a reduction of near-surface air-temperatures, which is attributed to the different atmospheric conditions during morning and evening. This study presents a new quantification of the city-wide impact of electric vehicles on the air temperature in a tropical urban area. The results may support policy-makers toward designing holistic solutions to address the challenge of climate change adaptation and mitigation in cities.
Effects of Different Temperatures on the Development and Reproduction of Sitobion miscanthi From Six Different Regions in China
Authors: Sun Jingxuan , Tan Xiaoling , Li Qian , Francis Frédéric , Chen Julian
Published: February 2022

The increase in temperature caused by global warming has greatly impacted plant growth and pest population dynamics worldwide, especially for wheat aphids. In this study,Sitobion miscanthiindividuals from six geographic populations located in different wheat-producing areas in China were compared with regard to their growth, development, survival, and reproductive under different temperature conditions (17, 22 and 27°C). A population life-table analysis and a correlation analysis between geographic factors andS. miscanthilongevity or fecundity were also performed. Temperature significantly affected the nymphal development duration (NDD), the adult longevity (ALY) and the fecundity (AFY) of the aphids, however, latitude can only affect the NDD and ALY. There is an obvious interaction between temperature and latitude on the NDD, ALY, and AFY. The NDD in the three northern populations was significantly shorter than that in the southern populations. The ALY in northern populations was significantly longer than that in southern populations at different temperatures. Except for Yinchuan population was no significantly different under different degrees, the ALY of other populations was significantly shortened at 27°C. The AFY of northern populations was significantly lower than that of southern populations at 22°C, while significantly higher at 27°C. With the increase of temperature, the fecundity of northern population gradually decreased from 17 to 22°C, while the southern population suddenly decreased at 27°C. The curves of survival rate (sxj) in southern populations were significantly shorter than that of northern population. Especially the populations in Suzhou and Wuhan, in which the survival rate decreased rapidly at 27°C. Age-specific survival rate (lx) of southern populations began to decline rapidly on 15 days of age at 27°C, while those of northern populations were not significantly affected until on 20 days of age. The highest peaks of age-stage fecundity (fxj), age-specific fecundity (mx), and age-specific net maternity (lxmx) were occurred in northern populations. In addition, there was a positive correlation between latitude and longevity under the three degrees, however, only at 27°C, there was a positive correlation between latitude and fecundity. Our result proved that the higher reproductive rate of southern population requires aphids to live at the suitable ambient temperature, and aphid populations in the north have a wider ecological amplitude. The results will be helpful for predicting the potential aphid outbreaks in China’s main wheat areas under suitable conditions.
How to Stay Cool: Early Acoustic and Thermal Experience Alters Individual Behavioural Thermoregulation in the Heat
Authors: Udino Eve , Mariette Mylene M.
Published: February 2022

Climate change is pushing organisms closer to their physiological limits. Animals can reduce heat exposure – and the associated risks of lethal hyperthermia and dehydration – by retreating into thermal refuges. Refuge use nonetheless reduces foraging and reproductive activities, and thereby potentially fitness. Behavioural responses to heat thus define the selection pressures to which individuals are exposed. However, whether and why such behavioural responses vary between individuals remains largely unknown. Here, we tested whether early-life experience generates inter-individual differences in behavioural responses to heat at adulthood. In the arid-adapted zebra finch, parents incubating at high temperatures emit “heat-calls,” which adaptively alter offspring growth. We experimentally manipulated individual early life acoustic and thermal experience. At adulthood, across two summers, we then repeatedly recorded individual panting behaviour, microsite use, activity (N = 2,402 observations for 184 birds), and (for a small subset, N = 23 birds) body temperature, over a gradient of air temperatures (26–38°C), in outdoor aviaries. We found consistent inter-individual variation in behavioural thermoregulation, and show for the first time in endotherms that early-life experience contributes to such variation. Birds exposed prenatally to heat-calls started panting at lower temperatures than controls but panted less at high temperatures. It is possible that this corresponds to a heat-regulation strategy to improve water saving at high temperature extremes, and/or, allow maintaining high activity levels, since heat-call birds were also more active across the temperature gradient. In addition, microsite use varied with the interaction between early acoustic and thermal experiences, control-call birds from cooler nests using the cooler microsite more than their hot-nest counterparts, whereas the opposite pattern was observed in heat-call birds. Overall, our study demonstrates that a prenatal acoustic signal of heat alters how individuals adjust behaviourally to thermal challenges at adulthood. This suggests that there is scope for selection pressures to act differently across individuals, and potentially strengthen the long-term fitness impact of early-life effects.
Wuling Mountains Function as a Corridor for Woody Plant Species Exchange Between Northern and Southern Central China
Authors: Wang Congrong , Zhou Tianyang , Qin Yuanzhi , Zhou Gang , Fei Yanan , Xu Yaozhan , Tang Zhiyao , Jiang Mingxi , Qiao Xiujuan
Published: February 2022

Aim

Wuling Mountains range from the northeast to southwest in Central China, a region with high habitat complexity and diversity that supports substantial plant species diversity. Connecting the northern subtropics to the mid-subtropics, Wuling Mountains also link the floras of Eastern and South-Western China. Despite a long-standing interest in how important role Wuling Mountains play in species exchange, patterns of plant species diversity in Wuling and their underlying drivers are still not well characterized. Here, the spatial distribution of woody plant species in this region is described and the role the Wuling Mountains play in structuring biodiversity in surrounding areas is explored.

Location

Wuling Mountains and adjacent regions, China.

Methods

Detailed distribution data for woody plant species in China were collected and mapped onto a raster grid of the Wuling Mountains and adjacent regions (a total of 820,000 km2) to analyze spatial patterns in species diversity, including α-diversity (species richness) and β-diversity (βsor). Unweighted pair-group method using arithmetic averages (UPGMA) clustering was used to divide the study region based on species composition. Canonical redundancy analysis was used to illustrate spatial patterns and species-environment relationships.

Results

Mountainous areas in the study region have high species richness as compared to other areas. Species exchanges occurred at a greater rate latitudinally vs. longitudinally, especially in Wuling Mountains. This suggests that Wuling Mountains may be an important ecological corridor for woody species, linking Northern and Southern Chinese floras. The study region was divided into six bioregions based on species composition: the Wuling Mountains Region, Nanling-Xuefengshan Mountains Region, Qinling-Dabashan Mountains Region, Sichuan Basin Region, Yangtze Plain Region and Yungui Plateau Region.

Main Conclusions

The Wuling Mountains Region acts as an ecological corridor for woody species, linking Northern and Southern China, and fostering biodiversity exchange and conservation in Central China.
A Prognostic Model for Predicting Tumor Mutation Burden and Tumor-Infiltrating Immune Cells in Bladder Urothelial Carcinoma
Authors: Wang Chengbang , Chen Shaohua , Li Songheng , Mi Hua
Published: February 2022

Tremendous progress has been made in development of immunotherapeutic approaches for treatment of bladder urothelial carcinoma (BLCA). However, efficacy and safety of these approaches remain unsatisfactory, necessitating further investigations for identification of indicators for predicting prognosis and efficacy. In this study, we downloaded transcriptomic and clinical data of BLCA patients from The Cancer Genome Atlas (TCGA) database, and identified differentially expressed genes (DEGs) between tumor and normal tissues. We incorporated these DEGs in an intersection analysis with immune-related genes (IRGs) obtained from the Immunology Database and Analysis Portal (ImmPort) database, and identified immune-related DEGs. These genes were subjected to Cox and least absolute shrinkage and selection operator (LASSO) regression analyses, then a prognostic model containing AHNAK, OAS1, NGF, PPY and SCG2 genes was constructed, for prediction of prognosis of BLCA and efficacy of immunotherapy. Finally, we explored the relationship between the prognostic model and tumor mutational burden (TMB), abundance of tumor-infiltrating immune cells (TICs) and immunotherapeutic targets, and found that patients with higher risk score (RS) had poorer prognosis and significantly lower levels of TMB. Patients in the low-RS group exhibited higher numbers of lymphoid cells, whereas those in the high-RS group exhibited higher proportions of myeloid cells. However, patients with high-RS tended to respond better to immunotherapy relative to those in the low-RS group. The constructed prognostic model provides a new tool for predicting prognosis of BLCA patients and efficacy of immunotherapy, offering a feasible option for management of the disease.
Benchmark of Data Processing Methods and Machine Learning Models for Gut Microbiome-Based Diagnosis of Inflammatory Bowel Disease
Authors: Kubinski Ryszard , Djamen-Kepaou Jean-Yves , Zhanabaev Timur , Hernandez-Garcia Alex , Bauer Stefan , Hildebrand Falk , Korcsmaros Tamas , Karam Sani , Jantchou Prévost , Kafi Kamran , Martin Ryan D.
Published: February 2022

Patients with inflammatory bowel disease (IBD) wait months and undergo numerous invasive procedures between the initial appearance of symptoms and receiving a diagnosis. In order to reduce time until diagnosis and improve patient wellbeing, machine learning algorithms capable of diagnosing IBD from the gut microbiome’s composition are currently being explored. To date, these models have had limited clinical application due to decreased performance when applied to a new cohort of patient samples. Various methods have been developed to analyze microbiome data which may improve the generalizability of machine learning IBD diagnostic tests. With an abundance of methods, there is a need to benchmark the performance and generalizability of various machine learning pipelines (from data processing to training a machine learning model) for microbiome-based IBD diagnostic tools. We collected fifteen 16S rRNA microbiome datasets (7,707 samples) from North America to benchmark combinations of gut microbiome features, data normalization and transformation methods, batch effect correction methods, and machine learning models. Pipeline generalizability to new cohorts of patients was evaluated with two binary classification metrics following leave-one-dataset-out cross (LODO) validation, where all samples from one study were left out of the training set and tested upon. We demonstrate that taxonomic features processed with a compositional transformation method and batch effect correction with the naive zero-centering method attain the best classification performance. In addition, machine learning models that identify non-linear decision boundaries between labels are more generalizable than those that are linearly constrained. Lastly, we illustrate the importance of generating a curated training dataset to ensure similar performance across patient demographics. These findings will help improve the generalizability of machine learning models as we move towards non-invasive diagnostic and disease management tools for patients with IBD.