bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiomics signatures of type 1 diabetes with and without albuminuria
Authors: Clos-Garcia Marc , Ahluwalia Tarunveer S. , Winther Signe A. , Henriksen Peter , Ali Mina , Fan Yong , Stankevic Evelina , Lyu Liwei , Vogt Josef K. , Hansen Torben , Legido-Quigley Cristina , Rossing Peter , Pedersen Oluf
Published: December 2022

Aims/hypothesis

To identify novel pathophysiological signatures of longstanding type 1 diabetes (T1D) with and without albuminuria we investigated the gut microbiome and blood metabolome in individuals with T1D and healthy controls (HC). We also mapped the functional underpinnings of the microbiome in relation to its metabolic role.

Methods

One hundred and sixty-one individuals with T1D and 50 HC were recruited at the Steno Diabetes Center Copenhagen, Denmark. T1D cases were stratified based on levels of albuminuria into normoalbuminuria, moderate and severely increased albuminuria. Shotgun sequencing of bacterial and viral microbiome in stool samples and circulating metabolites and lipids profiling using mass spectroscopy in plasma of all participants were performed. Functional mapping of microbiome into Gut Metabolic Modules (GMMs) was done using EggNog and KEGG databases. Multiomics integration was performed using MOFA tool.

Results

Measures of the gut bacterial beta diversity differed significantly between T1D and HC, either with moderately or severely increased albuminuria. Taxonomic analyses of the bacterial microbiota identified 51 species that differed in absolute abundance between T1D and HC (17 higher, 34 lower). Stratified on levels of albuminuria, 10 species were differentially abundant for the moderately increased albuminuria group, 63 for the severely increased albuminuria group while 25 were common and differentially abundant both for moderately and severely increased albuminuria groups, when compared to HC. Functional characterization of the bacteriome identified 23 differentially enriched GMMs between T1D and HC, mostly involved in sugar and amino acid metabolism. No differences in relation to albuminuria stratification was observed. Twenty-five phages were differentially abundant between T1D and HC groups. Six of these varied with albuminuria status. Plasma metabolomics indicated differences in the steroidogenesis and sugar metabolism and circulating sphingolipids in T1D individuals. We identified association between sphingolipid levels and Bacteroides sp. abundances. MOFA revealed reduced interactions between gut microbiome and plasma metabolome profiles albeit polar metabolite, lipids and bacteriome compositions contributed to the variance in albuminuria levels among T1D individuals.

Conclusions

Individuals with T1D and progressive kidney disease stratified on levels of albuminuria show distinct signatures in their gut microbiome and blood metabolome.
WF SS-OCTA for detecting diabetic retinopathy and evaluating the effect of photocoagulation on posterior vitreous detachment
Authors: Gong Yi , Hu Liying , Wang Linni , Shao Yan , Li Xiaorong
Published: December 2022

Purpose

This study aimed to assess the clinical usefulness of widefield swept source optical coherence tomography angiography (WF SS-OCTA) for detecting microvasculature lesions in diabetic retinopathy (DR) by comparing it with ultra-widefield fluorescein angiography (UWFFA) and to investigate the effect of panretinal photocoagulation (PRP) on posterior vitreous detachment (PVD) status.

Methods

Patients with severe non-proliferative DR (NPDR) or proliferative DR (PDR) who were initially treated with PRP were enrolled. They underwent WF SS-OCTA with a 12×12-mm scan pattern of five visual fixations at baseline and at least a 3-month follow-up after PRP treatment. Patients with no contraindications underwent imaging with UWFFA within a week. Images were evaluated using two methods for the areas of the visible field of view (FOV), non-perfusion area (NPA), presence of neovascularization of the disc (NVD), neovascularization elsewhere (NVE), and PVD status.

Results

In total, 44 eyes of 28 patients with DR that were initially treated with PRP were analyzed. The FOV of the UWFFA was significantly wider than that of the WF SS-OCTA. The quantitative measurement of the NPAs was consistent between the two methods. NPAs more than 5DA outside the panoramic OCTA imaging area were detected in 1 eye with NPDR (8.3%) and in 10 eyes with PDR (47.8%). WF SS-OCTA had high detection rates for NVDs and NVEs, with a low rate of false positives. After PRP treatment, no eyes indicated progression in the PVD stages around the macula, optical disc, or NVEs at the short follow-up.

Conclusion

WF SS-OCTA is clinically useful for evaluating NPAs and neovascularization in DR. PRP treatment does not induce PVD development in the short term.
A review of the genetics and epigenetics of central precocious puberty
Authors: Moise-Silverman Joshua , Silverman Lawrence A.
Published: December 2022

Gonadotrophin dependent sexual precocity, commonly referred to as central precocious puberty (CPP), results from a premature reactivation of the hypothalamic-pituitary-gonadal (HPG) axis before the normal age of pubertal onset. CPP is historically described as girls who enter puberty before the age of eight, and boys before the age of nine. Females are more likely to be diagnosed with idiopathic CPP; males diagnosed with CPP have a greater likelihood of a defined etiology. These etiologies may include underlying CNS congenital defects, tumors, trauma, or infections as well as environmental, genetic, and epigenetic factors. Recently, genetic variants and mutations which may cause CPP have been identified at both the level of the hypothalamus and the pituitary. Single nucleotide polymorphisms (SNPs), monogenetic mutations, and modifications of the epigenome have been evaluated in relationship to the onset of puberty; these variants are thought to affect the development, structure and function of GnRH neurons which may lead to either precocious, delayed, or absent pubertal reactivation. This review will describe recent advances in the field of the genetic basis of puberty and provide a clinically relevant approach to better understand these varying etiologies of CPP.
Small RNA perspective of physical exercise-related improvement of male reproductive dysfunction due to obesity
Authors: Lin Tingting , Zhang Shuyu , Zhou Yuchuan , Wu Ligang , Liu Xinmei , Huang Hefeng
Published: December 2022

Purpose

To study whether physical exercise can effectively ameliorate obesity-induced abnormalities in male fertility and provide a new perspective on the role of small noncoding RNAs in spermatogenesis in obese male mice.

Methods

In this study, four-week-old C57/Bl6 male mice were randomly allocated to receive a control diet, a high-fat diet or physical exercise intervention for 40 weeks. Purified round spermatids and spermatozoa were obtained after intervention. Sperm motility, concentration, the ability of the sperm to undergo capacitation and acrosome reaction were assessed. Small RNA sequencing was conducted on round spermatids and spermatozoa. The small noncoding RNAs expression pattern was systematically analyzed.

Results

The spermatozoa concentration and percentage of motile spermatozoa, the capacitation and acrosome reaction, and the reproductive success rate, including mating success and pregnancy success, were decreased or delayed in the obesity group compared with controls. Physical exercise was able to restore the parameters to normal levels. Three microRNAs were consistently upregulated and 5 were downregulated in round spermatids and epididymal spermatozoa between the obesity and control groups.

Conclusions

This report provides evidence that the adverse effects of obesity could be offset after physical exercise. small noncoding RNAs, especially microRNAs in germ cells, may play an important role in the effects of obesity and physical exercise on spermatozoa.
Visit-to-visit variability in triglyceride-glucose index and diabetes: A 9-year prospective study in the Kailuan Study
Authors: Wang Xianxuan , Chen Yanjuan , Huang Zegui , Cai Zefeng , Yu Xinran , Chen Zekai , Li Linyao , Chen Guanzhi , Wu Kuangyi , Zheng Huancong , Wu Shouling , Chen Youren
Published: December 2022

Instruction/Aims

It is unknown whether variability in the triglyceride-glucose index (TyG-index) is associated with the risk of diabetes. Here, we sought to characterize the relationship between TyG-index variability and incident diabetes.

Methods

We performed a prospective study of 48,013 participants in the Kailuan Study who did not have diabetes. The TyG-index was calculated as ln [triglyceride (TG, mg/dL) concentration × fasting blood glucose concentration (FBG, mg/dL)/2]. The TyG-index variability was assessed using the standard deviation (SD) of three TyG-index values that were calculated during 2006/07, 2008/09, and 2010/11. We used the Cox proportional hazard models to analyze the effect of TyG-index variability on incident diabetes.

Results

A total of 4,055 participants were newly diagnosed with diabetes during the study period of 8.95 years (95% confidence interval (CI) 8.48–9.29 years). After adjustment for confounding factors, participants in the highest and second-highest quartiles had significantly higher risks of new-onset diabetes versus the lowest quartile, with hazard ratios (95% CIs) of 1.18 (1.08–1.29) and 1.13 (1.03–1.24), respectively (P trend< 0.05). These higher risks remained after further adjustment for the baseline TyG-index.

Conclusions

A substantial fluctuation in TyG-index is associated with a higher risk of diabetes in the Chinese population, implying that it is important to maintain a normal and consistent TyG-index.
The role of growth hormone in assisted reproduction
Authors: Quaas Alexander M. , Penzias Alan S. , Adashi Eli Y.
Published: December 2022

In contemporary ART, the use of “add-ons” during ovarian stimulation has increased, especially in poor responders. Growth Hormone (GH) is an adjunctive therapy that has been studied extensively in the translational and clinical setting, with an ongoing scientific debate over its effectiveness and optimal use. In this review, we aim to provide an overview of the physiologic basis for the use of GH in ART, and to summarize the latest evidence regarding its clinical use, primarily as an adjunct to ovarian stimulation, but also in the IVF lab and with regards to its effects on the endometrium.
Re-understanding and focusing on normoalbuminuric diabetic kidney disease
Authors: An Na , Wu Bi-tao , Yang Yu-wei , Huang Zheng-hong , Feng Jia-fu
Published: December 2022

Diabetes mellitus (DM) has grown up to be an important issue of global public health because of its high incidence rate. About 25% of DM patients can develop diabetic foot/ulcers (DF/DFU). Diabetic kidney disease (DKD) is the main cause of end-stage kidney disease (ESKD). DF/DFU and DKD are serious complications of DM. Therefore, early diagnosis and timely prevention and treatment of DF/DFU and DKD are essential for the progress of DM. The clinical diagnosis and staging of DKD are mostly based on the urinary albumin excretion rate (UAER) and EGFR. However, clinically, DKD patients show normoalbuminuric diabetic kidney disease (NADKD) instead of clinical proteinuria. The old NADKD concept is no longer suitable and should be updated accordingly with the redefinition of normal proteinuria by NKF/FDA. Based on the relevant guidelines of DM and CKD and combined with the current situation of clinical research, the review described NADKD from the aspects of epidemiology, pathological mechanism, clinical characteristics, biomarkers, disease diagnosis, and the relationship with DF/DFU to arouse the new understanding of NADKD in the medical profession and pay attention to it.
Regional organic matter and mineral dust are the main components of atmospheric aerosols over the Nam Co station on the central Tibetan Plateau in summer
Authors: Zhang Haotian , Tian Pengfei , Kang Chenliang , Guo Yumin , Yu Zeren , Lu Gefei , Tang Chenguang , Du Tao , Wang Jiayun , Zhang Zhida , Cao Xianjie , Liang Jiening , Shi Jinsen
Published: December 2022

The transport of air pollutants from areas surrounding the Tibetan Plateau (TP) has recently been studied. However, the major sources of atmospheric total suspended particulate matter (TSP) on the central TP remain unclear due to a lack of in-situ observations on aerosol physico-chemical properties. Therefore, to quantitatively investigate the physico-chemical properties and reveal the major sources of atmospheric aerosols, a comprehensive field campaign was conducted at the site of Nam Co from August 6 to September 11, 2020. Aerosol loading was low during the campaign with average TSP mass concentration, scattering coefficient at 550 nm, and absorption coefficient at 670 nm being 10.11 ± 5.36 μg m−3, 1.71 ± 1.36 Mm−1, and 0.26 ± 0.20 Mm−1, respectively. Organic matter (63.9%) and mineral dust (27.8%) accounted for most of the TSP mass concentrations. The average scattering Ångström exponent of 0.59 ± 0.14 reflected the influence of mineral dust, and the elemental fractions and the results of enrichment factor illustrated that crustal materials were the main contributors of mineral dust. The organic to elemental carbon ratio of 15.33 is probably caused by the aging that occurs during the transport of aerosols. The strong correlation between organic carbon and Ca2+ and the results of the electron microscopy analysis of single particles indicated that organic carbon and mineral dust had the same sources; however, the weak relation between mineral dust and wind speed indicated that local wind erosion was not the main contributor to the mineral dust. The potential source contribution function further illustrated that the summertime TSP in the central TP was mainly characterized by background biomass and mineral dust aerosols originating regionally from the ground within the TP.
Changes in crop water consumption in Xinjiang of China from 1989 to 2018: A Logarithmic Mean Divisia Index decomposition analysis
Authors: Li Yinbo , Deng Mingjiang
Published: December 2022

Xinjiang, located in Northwestern China, is the important production base of various crops with high water consumption. The quantitative contribution of driving factors to crop water consumption has not been investigated in Xinjiang. In this study, the Logarithmic Mean Divisia Index method is used to quantitatively analyze the effect of five factors (population, planting structure, agricultural economics, water intensity, and industrial structure) to crop water consumption during 1989–2018. The results show that 1) crop water consumption has increased from 10.363 to 37.226 billion m3 with a rate of 0.932 billion m3/a in 1989–2018. Its increased trend can be divided into two stages: a slow increase at a rate of 0.425 million m3/a in 1989–2003 and a quick expansion at a rate of 1.310 million m3/a in 2004–2018. 2) The increase of population and agricultural economics both promote crop water consumption, whereas changes in planting structure and water intensity both inhibit crop water consumption. Their contributions are 0.213, 2.068, −0.007, and −0.134 billion m3, respectively. The increased agricultural economics and the decreased water intensity more significantly changed crop water consumption in 2004–2018 than in 1989–2003. 3) The total effects of five factors on crops varied at each stage. All crops (except wheat) have a promoting effect on an increase in crop water consumption with the largest value in cotton (0.378 million m3) in 1989–2003. The effect of the five factors on crops (except soybean and medicago) is positive (1.404 million m3), and the highest value is shown in cotton during 2004–2018. The results illustrate the contribution of the five factors of crop water consumption and provide references for local agricultural water saving in Xinjiang.
Bioinformatics analysis of genes related to ferroptosis in hepatic ischemia-reperfusion injury
Authors: Sun Shuo , Xue Jianming , Guo Yunfei , Li Jianling
Published: December 2022

Background: Primary liver cancer is the sixth most commonly diagnosed cancer and the third leading cause of cancer death worldwide in 2020, and it ranks fifth in global incidence. Liver resection or liver transplantation are the two most prominent surgical procedures for treating primary liver cancer. Both inevitably result in HIRI, causing severe complications for patients and affecting their prognosis and quality of survival. Ferroptosis, a newly discovered mode of cell death, is closely related to HIRI. We used bioinformatics analysis to explore the relationship between the two further.

Methods: The GEO database dataset GSE112713 and the FerrDB database data were selected to use bioinformatic analysis methods (difference analysis, FRGs identification, GO analysis, KEGG analysis, PPI network construction and analysis, Hub gene screening with GO analysis and KEGG analysis, intergenic interaction prediction, drug-gene interaction prediction, miRNA prediction) for both for correlation analysis. The GEO database dataset GSE15480 was selected for preliminary validation of the screened Hub genes.

Results: We analysed the dataset GSE112713 for differential gene expression before and after hepatic ischemia-reperfusion and identified by FRGs, yielding 11 genes. These 11 genes were subjected to GO, and KEGG analyses, and PPI networks were constructed and analysed. We also screened these 11 genes again to obtain 5 Hub genes and performed GO analysis, KEGG analysis, intergenic interaction prediction, drug-gene interaction prediction, and miRNA prediction on these 5 Hub genes. Finally, we obtained preliminary validation of all these 5 Hub genes by dataset GSE15480.

Conclusion: There is a close relationship between HIRI and ferroptosis, and inhibition of ferroptosis can potentially be a new approach to mitigate HIRI treatment in the future.
Across-breed genetic investigation of canine hip dysplasia, elbow dysplasia, and anterior cruciate ligament rupture using whole-genome sequencing
Authors: Binversie Emily E. , Momen Mehdi , Rosa Guilherme J. M. , Davis Brian W. , Muir Peter
Published: December 2022

Here, we report the use of genome-wide association study (GWAS) for the analysis of canine whole-genome sequencing (WGS) repository data using breed phenotypes. Single-nucleotide polymorphisms (SNPs) were called from WGS data from 648 dogs that included 119 breeds from the Dog10K Genomes Project. Next, we assigned breed phenotypes for hip dysplasia (Orthopedic Foundation for Animals (OFA) HD,n= 230 dogs from 27 breeds; hospital HD,n= 279 dogs from 38 breeds), elbow dysplasia (ED,n= 230 dogs from 27 breeds), and anterior cruciate ligament rupture (ACL rupture,n= 279 dogs from 38 breeds), the three most important canine spontaneous complex orthopedic diseases. Substantial morbidity is common with these diseases. Previous within- and between-breed GWAS for HD, ED, and ACL rupture using array SNPs have identified disease-associated loci. Individual disease phenotypes are lacking in repository data. There is a critical knowledge gap regarding the optimal approach to undertake categorical GWAS without individual phenotypes. We considered four GWAS approaches: a classical linear mixed model, a haplotype-based model, a binary case-control model, and a weighted least squares model using SNP average allelic frequency. We found that categorical GWAS was able to validate HD candidate loci. Additionally, we discovered novel candidate loci and genes for all three diseases, includingFBX025, IL1A, IL1B, COL27A1, SPRED2(HD),UGDH,FAF1(ED),TGIF2(ED & ACL rupture), andIL22,IL26,CSMD1,LDHA, andTNS1(ACL rupture). Therefore, categorical GWAS of ancestral dog populations may contribute to the understanding of any disease for which breed epidemiological risk data are available, including diseases for which GWAS has not been performed and candidate loci remain elusive.
The different damage patterns of short-, middle- and long-range connections between patients with relapse-remitting multiple sclerosis and neuromyelitis optica spectrum disorder
Authors: Chen Xiaoya , Peng Yuling , Zheng Qiao , Luo Dan , Han Yongliang , Luo Qi , Zhu Qiyuan , Luo Tianyou , Li Yongmei
Published: December 2022

Objective

To investigate the differences in short-, middle- and long-range connections between patients with relapse-remitting multiple sclerosis (RRMS) and neuromyelitis optica spectrum disorder (NMOSD), and their correlation with brain tissue volume, structural and functional network parameters.

Methods

A total of 51 RRMS, 42 NMOSD and 56 health controls (HC) were recruited. Of these 25 RRMS (median: 1.37 years) and 20 NMOSD (median: 1.25 years) patients were also studied at follow-up. The whole-brain fiber connection was divided into three groups according to the trisected lengths of the tract in HC group, including short-, middle- and long-range connections. The brain tissue features (including total brain tissue and deep grey matter volumes) and parameters of DTI and functional networks (including the shortest path, clustering coefficient, local efficiency and global efficiency) were calculated. The differences in fiber number (FN) and average fractional anisotropy (FA) were compared between RRMS and NMOSD by the One-way ANOVA and post hoc tests. The correlation between the FN or FA and the brain tissue volume, DTI and functional network parameters were further analyzed by Pearson analysis.

Results

Compared to HC and NMOSD, the total number of fibers in RRMS was decreased, including the reduced FN of middle- and long-range connections, but increased FN of short-range connections. Compared to HC, the FA of three fibers in RRMS and NMOSD were reduced significantly, and the decrease of FA in RRMS was greater than in NMOSD. There were correlations between the FN of short-, and long-range connections and the atrophy of whole brain tissue in two diseases and structural network topological parameters in RRMS. Additionally, there was no significant difference of FN and FA in short-, middle- and long-range connections between the baseline and follow-up in two diseases.

Conclusions

RRMS and NMOSD patients have different patterns of fiber connection damage. The FN of different lengths in RRMS and NMOSD patients may be associated with brain atrophy. The FN and FA of different lengths may explain the decreased efficiency of the structural network in RRMS patients. In the short-term follow-up, neither has worsened damage of different fibers in two diseases.
Interferon-inducible SAMHD1 restricts viral replication through downregulation of lipid synthesis
Authors: An Ni , Ge Qinghua , Shao Huihan , Li Quanjie , Guo Fei , Liang Chen , Li Xiaoyu , Yi Dongrong , Yang Long , Cen Shan
Published: December 2022

Background

Type I interferon (IFN) inhibits virus infection through multiple processes. Recent evidence indicates that IFN carries out its antiviral activity through readjusting of the cellular metabolism. The sterile alpha motif and histidine-aspartate domain containing protein 1 (SAMHD1), as an interferon-stimulated gene (ISG), has been reported to inhibit a number of retroviruses and DNA viruses, by depleting dNTPs indispensable for viral DNA replication. Here we report a new antiviral activity of SAMHD1 against RNA viruses including HCV and some other flaviviruses infection.

Methods

Multiple cellular and molecular biological technologies have been used to detect virus infection, replication and variation of intracellular proteins, including western blotting, qRT-PCR, Gene silencing, immunofluorescence, etc. Besides, microarray gene chip technology was applied to analyze the effects of SAMHD1 overexpression on total expressed genes.

Results

Our data show that SAMHD1 down-regulates the expression of genes related to lipid bio-metabolic pathway, accompanied with impaired lipid droplets (LDs) formation, two events important for flaviviruses infection. Mechanic study reveals that SAMHD1 mainly targets on HCV RNA replication, resulting in a broad inhibitory effect on the infectivity of flaviviruses. The C-terminal domain of SAMHD1 is showed to determine its antiviral function, which is regulated by the phosphorylation of T592. Restored lipid level by overexpression of SREBP1 or supplement with LDs counteracts with the antiviral activity of SAMHD1, providing evidence supporting the role of SAMHD1-mediated down-regulation of lipid synthesis in its function to inhibit viral infection.

Conclusion

SAMHD1 plays an important role in IFN-mediated blockade of flaviviruses infection through targeting lipid bio-metabolic pathway.
Akkermansia muciniphila suppressing nonalcoholic steatohepatitis associated tumorigenesis through CXCR6+ natural killer T cells
Authors: Li Tao , Lin Xinlong , Shen Binhai , Zhang Wujian , Liu Yangyang , Liu Hongbin , Wang Ye , Zheng Lijun , Zhi Fachao
Published: December 2022

Introduction

Gut microbiota plays a crucial role in the development and progression of nonalcoholic steatohepatitis (NASH) and associated hepatocellular carcinoma (HCC). Akkermansia muciniphila was reported to inhibit inflammation-associated cancer in the intestine. The anti-NASH ability of A. muciniphila has recently been found. Thus, we were to investigate whether supplementation of A. muciniphila could prevent NASH-associated HCC.

Methods

In a model we called STAM, male C57BL/6J mice were subcutaneously injected with 200 µg streptozotocin at 4 days after birth, and fed with high-fat diet at 4 weeks of age to induce NASH-associated HCC. Faeces from mice and patients with NASH-related HCC were collected for 16S rRNA sequencing. STAM mice were orally administered either saline or A. muciniphila twice a day starting at 4 or 10 weeks of age. The effects of A. muciniphila on the immune responses were also evaluated.

Results

Patients and mice with NASH-related HCC showed significantly reduced gut A. muciniphila in comparison to healthy controls. Administration of breast milk-isolated A. muciniphila (AM06) but not feces-isolated A. muciniphila (AM02) could improve NASH severity. Interestingly, breast milk-isolated A. muciniphila treatment suppressed the progression of NASH to HCC, accompanied with an increased hepatic CXCR6+ natural killer T (NKT) cell and decreased macrophage infiltration. The antitumor ability of A. muciniphila was not evident in NKT cell-deficient mice (CD1d-/- and CXCR6-/-). In vitro, A. muciniphila promoted the killing of hepG2 cells by NKT cells.

Discussion

Our study will provide the rationale for the application of A. muciniphila to treat NASH and for the prevention of its progression to HCC.
A novel enterocyte-related 4-gene signature for predicting prognosis in colon adenocarcinoma
Authors: Cheng Xuehua , Wei Yong , Fu Yugang , Li Jiacheng , Han Li
Published: December 2022

Background

Colon adenocarcinoma (COAD) is a fatal disease, and its cases are constantly increasing worldwide. Further, the therapeutic and management strategies for patients with COAD are still unsatisfactory due to the lack of accurate patient classification and prognostic models. Therefore, our study aims to identify prognostic markers in patients with COAD and construct a cell subtype-specific prognostic model with high accuracy and robustness.

Methods

Single-cell transcriptomic data of six samples were retrieved from the Gene expression omnibus (GEO) database. The cluster annotation and cell-cell communication analysis identified enterocytes as a key player mediating signal communication networks. A four-gene signature prognostic model was constructed based on the enterocyte-related differentially expressed genes (ERDEGs) in patients with COAD of the Cancer Genome Atlas cohort. The prognostic model was validated on three external validation cohorts from the GEO database. The correlation between immune cell infiltration, immunotherapy response, drug sensitivity, and the four-gene signature prognostic model was investigated. Finally, immunohistochemistry (IHC) was performed to determine the expression of the four genes.

Results

We found that the proportion of epithelial cells was obviously large in COAD samples. Further analysis of epithelial cells showed that the activity of the enterocytes was highest in the cell-cell communication network. Based on enterocyte data, 30 ERDEGs were identified and a 4-gene prognostic model including CPM, CLCA4, ELOVL6, and ATP2A3 was developed and validated. The risk score derived from this model was considered as an independent variable factor to predict overall survival. The patients were divided into high- and low-risk groups based on the median riskscore value. The correlation between immune cell infiltration, immunotherapy response, immune status, clinical characteristics, drug sensitivity, and risk score was analyzed. IHC confirmed the expression of signature genes in tissues from normal individuals, patients with polyps, and COAD.

Conclusion

In this study, we constructed and validated a novel four-gene signature prognostic model, which could effectively predict the response to immunotherapy and overall survival in patients with COAD. More importantly, this model provides useful insight into the management of colon cancer patients and aids in designing personalized therapy.
Impact of exposure to malaria and nutritional status on responses to the experimental malaria vaccine ChAd63 MVA ME-TRAP in 5-17 month-old children in Burkina Faso
Authors: Morter Richard , Tiono Alfred B. , Nébié Issa , Hague Oliver , Ouedraogo Alphonse , Diarra Amidou , Viebig Nicola K. , Hill Adrian V. S. , Ewer Katie J. , Sirima Sodiomon B.
Published: December 2022

The experimental malaria vaccine ChAd63 MVA ME-TRAP previously showed protective efficacy against Plasmodium falciparum infection in Phase IIa sporozoite challenge studies in adults in the United Kingdom and in a Phase IIb field efficacy trial in Kenyan adults. However, it failed to demonstrate efficacy in a phase IIb trial in 5-17 month-old children in an area of high malaria transmission in Burkina Faso. This secondary analysis investigated whether exposure to malaria or nutritional status might be associated with reduced responses to vaccination in this cohort. Parasite blood smears and anti-AMA-1 IgG titres were used to assess history of exposure to malaria and weight-for-length Z scores were calculated to assess nutritional status. Differences in vaccine-specific anti-TRAP IgG titre and ex vivo IFNγ ELISpot response were measured between groups. In total, n = 336 volunteers randomised to receive the experimental vaccine regimen were included in this analysis. A positive smear microscopy result was associated with reduced anti-TRAP IgG titre (geometric mean titre: 2775 (uninfected) vs 1968 (infected), p = 0.025), whilst anti-AMA-1 IgG titres were weakly negatively correlated with reduced ex vivo IFNγ ELISpot response (r = -0.18, p = 0.008). Nutritional status was not associated with either humoral or cellular immunogenicity. Vaccine efficacy was also measured separately for vaccinees with positive and negative blood smears. Although not significant in either group compared to controls, vaccine efficacy measured by Cox hazard ratio was higher in uninfected compared to infected individuals (19.8% [p = 0.50] vs 3.3% [p = 0.69]). Overall, this data suggests exposure to malaria may be associated with impaired vaccine immunogenicity. This may have consequences for the testing and eventual deployment of various vaccines, in areas with high endemicity for malaria.

Trial Registration

Pactr.org, identifier PACTR201208000404131; ClinicalTrials.gov, identifier NCT01635647.
A vortex-implanted initialization scheme for the mesoscale eddy prediction: Idealized experiments
Authors: Zhu Yuhang , Peng Shiqiu , Li Yineng
Published: December 2022

Mesoscale eddy prediction has been a big challenge to oceanographers and marine environment forecasters. Although the traditional initialization for the prediction, i.e., through assimilating the satellite-derived sea level anomalies (SLA) into a model, has some improvement, it is yet unable to predict well the main characteristics of a mesoscale eddy, including its three-dimensional (3D) structure, moving track, size, and intensity. In this study, a vortex-implanted initialization scheme for the mesoscale eddy prediction (VISTMEP) is developed. With the VISTMEP, a bogus vortex is first constructed in terms of 3D SLA-derived currents, and then it is implanted into the model initial field to obtain a more accurate 3D current field of a mesoscale eddy for prediction. The results from idealized experiments show that the VISTMEP can significantly improve prediction of the mesoscale eddy with a longer valid prediction length up to 30 days compared to the experiment with the traditional initialization. Detailed analysis indicates that, as the model is integrated forward, a more “realistic” 3D structure of the eddy in terms of both current and temperature fields is formed when the VISTMEP is employed, leading to the improvement of the eddy prediction regarding to the moving track, size, and intensity of the eddy, which is largely influenced by the accuracy of the initial current field of the eddy obtained by the VISTMEP. This study provides an innovative method for the mesoscale eddy prediction, which could have great potential application in operational services of the marine environments.
A three-dimensional experimental study on bank retreat: The coupled role of seepage and surface flow
Authors: Wang Keyu , Gong Zheng , Zhao Kun , Tang Shuai , Zhang Kaili
Published: December 2022

The coupled role of seepage and surface flow on bank retreat has long been neglected, partly due to the concealment and complexity of seepage erosion. To fill this gap, we set up a three-dimensional laboratory experiment to explore bank retreat process in response to seepage and surface flow. During each experiment, we measured the changes of total soil stress, matric suction, and water content within the bank, as well as flow velocity and suspended sediment concentration near the bank. Results show that a rapid decrease in matric suction, the bank toe undercutting consequent to seepage erosion, the formation of tension crack on the bank top, and the occurrence of toppling or shear failure is the typical sequence of the observed bank retreat process under seepage flow. The inclusion of surface flow erodes slump blocks and so promotes cantilever formation, leading to additional bank failure. Compared with the case where only seepage is considered, the frequency of toppling failure under the coupled effect of seepage and surface flow decreases, but the contribution to the bank retreat increases by 37 %. The time taken to collapse in three-dimensional experiments is at least 1.5 h earlier than that of two-dimensional experiments, indicating the importance of preferential flow pathways of seepage. Overall, this research illustrates how surface flow interacts with seepage flow to control bank retreat process and is indeed a first step toward a fully understanding of multifactor-driven bank retreat.
Determination of nitrogen content in Ulva fenestrata by color image analysis – a rapid and cost-efficient method to estimate nitrogen content in seaweeds
Authors: Stedt Kristoffer , Toth Gunilla B. , Davegård Johan , Pavia Henrik , Steinhagen Sophie
Published: December 2022

There is an increasing interest in the cultivation of seaweeds for food and feed, and the seaweed aquaculture industry is rapidly developing. The nutritional status of the seaweeds is important to ensure a good quality crop. Cost-efficient and straightforward methods for farmers to analyze their crop are essential for the successful development of the industry. In this study, we developed non-destructive, labor- and cost-efficient models to estimate the nitrogen content in the crop seaweed Ulva fenestrata by color image analysis. We quantified tissue nitrogen content and thallus color in sea-farmed seaweed every week throughout a whole cultivation season (15 consecutive weeks) and analyzed data with linear regression models. We showed that color image analysis accurately estimated the nitrogen content in the seaweed (R2 = 0.944 and 0.827 for fresh tissue and dried powder, respectively), and through tenfold cross validation we showed that the developed models were robust and precise. Based on these models, we developed a web-based application that automatically analyzes the nitrogen content of U. fenestrata. Furthermore, we produced a color guide that can easily be brought to the farm for onsite crude estimation of the nitrogen content of U. fenestrata. Our results demonstrate that color can be a powerful tool for seaweed farmers (and researchers) to estimate seaweeds’ nutritional status. We anticipate that similar models can be developed for other commercially interesting seaweed species.
The increasing big gap of carbon sink between the western and eastern Pacific in the last three decades
Authors: Zhong Guorong , Li Xuegang , Song Jinming , Qu Baoxiao , Wang Fan , Wang Yanjun , Zhang Bin , Tian Detong , Ma Jun , Yuan Huamao , Duan Liqin , Li Ning , Wang Qidong , Xing Jianwei
Published: December 2022

The Pacific Ocean is one of the important carbon sink regions, and there is a significant west-east difference in sea-air CO2 flux. However, the influence of the long-standing greater CO2 uptakes in the western Pacific than in the east and the dynamic change of this west-east difference remain unclear. In this paper, using the gridded surface ocean pCO2 product constructed by the stepwise FFNN algorithm, we reported an increasing west-east CO2 flux difference from 0.41 PgC yr-1 in 1992 to 0.73 PgC yr-1 in 2020. This increase was mainly attributed to the strengthening western Pacific carbon sink and relatively stable eastern Pacific carbon source. During El Nino events, the west-east CO2 flux difference decreased significantly in a few years, and it then rose back rapidly when El Nino events ended. In addition, the increasing west-east difference in CO2 uptakes during the last three decades did not lead to a higher acidification speed in the western surface temperate Pacific than the east. The greater CO2 absorbed in the west was mainly transported to the deeper waters and caused a more significant carbon inventory change at 200-600 m than the eastern Pacific.
Investigation on temperature shrinkage characteristics of the combined structure in asphalt pavement
Authors: Jiangcai Chen , Zhiwei Li , Zihong Zhao , Xiaofeng Huang , Jie Chen , Zhiyang Liu
Published: December 2022

The temperature shrinkage of materials primarily causes transverse cracking. Current research mainly focuses on the temperature shrinkage of single materials. This work aims to analyze the effect of the structural combination on temperature shrinkage. To this end, the temperature rise method was first discussed to measure the shrinkage coefficient to replace the traditional temperature drop method. Then, the temperature shrinkage coefficients of the lime–fly ash-stabilized macadam, and ATB and AC asphalt mixtures were measured. The effect of gradation types, lime–fly ash content, and nominal maximum aggregate size on the temperature shrinkage was studied. Finally, the temperature shrinkage of composite structural characteristics was analyzed. The results show that the difference between the temperature shrinkage coefficients obtained by temperature rise and drop methods was relatively small. Thus, the temperature rise method can be used to measure the temperature shrinkage coefficient. In addition, the lime–fly ash-stabilized macadam with the suspended dense gradation or a higher lime–fly ash content has the largest temperature shrinkage strain. The suspended dense gradation should be avoided, and the content of lime–fly ash should be approximately reduced to control the temperature shrinkage strain of the semi-rigid base course. As for the asphalt mixture, the temperature shrinkage strain increased with the decrease in the nominal maximum aggregate size. The asphalt mixture with a larger nominal maximum aggregate size should be given priority to control the temperature shrinkage. Finally, when combined with the base course or surface layer, the temperature shrinkage of the base course was promoted by the surface layer, while the base course inhibited the surface layer. Meanwhile, the mutual influence between the semi-rigid base course and the surface layer was more substantial than that of the mutual influence between the flexible base course and surface layer.
Case report: Cutaneous pseudolymphoma caused by a Leishmania infantum infection in a patient treated with anti-TNF antibody for plaque psoriasis
Authors: Scholl Sarah , Schuster Daniel , Technau-Hafsi Kristin , Stete Katarina , Rieg Siegbert , May Annette M. , Bogdan Christian , Schauer Franziska
Published: December 2022

For psoriasis, which affects up to 2% of the population and adalimumab is approved from the age of 4 years. Here, we present a middle-aged Italian man with long-term history of plaque psoriasis and psoriasis arthropathica and adalimumab therapy. He developed ulcers or nodules within the psoriatic plaques, resembling cutaneous infection with Leishmania infantum. TNF and other cytokines such as IL-12 and IFN-γ are central in the early control of the infection. Discontinuation of the anti-TNF-treatment resolved the infection without specific therapy.
Hot topics on fecal microbiota transplantation for the treatment of inflammatory bowel disease
Authors: Zhang Xiaochen , Ishikawa Dai , Ohkusa Toshifumi , Fukuda Shinji , Nagahara Akihito
Published: December 2022

Inflammatory bowel disease (IBD) is a chronic intestinal mucosal inflammatory disease with complex etiology. Traditional anti-inflammatory treatment regimens have yielded unsatisfactory results. As research continues to deepen, it has been found that the gut microbiota of patients with IBD is generally altered. The presence of microorganisms in the human gastrointestinal tract is inextricably linked to the regulation of health and disease. Disruption of the microbiotic balance of microbiota in the gastrointestinal tract is called dysbiosis, which leads to disease. Therefore, in recent years, the exploration of therapeutic methods to restore the homeostasis of the gut microbiota has attracted attention. Moreover, the use of the well-established fecal microbiota transplantation (FMT) regimen for the treatment of Clostridioides difficile infection has attracted the interest of IBD researchers. Therefore, there are an increasing number of clinical studies regarding FMT for IBD treatment. However, a series of questions regarding FMT in the treatment of IBD warrants further investigation and discussion. By reviewing published studies, this review explored hot topics such as the efficacy, safety, and administration protocol flow of FMT in the treatment of IBD. Different administration protocols have generally shown reassuring results with significant efficacy and safety. However, the FMT treatment regimen needs to be further optimized. We believe that in the future, individual customized or standard FMT implementation will further enhance the relevance of FMT in the treatment of IBD.
Neutrophil phenotypes implicated in the pathophysiology of post-traumatic sepsis
Authors: Mizugaki Asumi , Wada Takeshi , Tsuchida Takumi , Oda Yoshitaka , Kayano Katsuhide , Yamakawa Kazuma , Tanaka Shinya
Published: December 2022

Background

The disruption of immune homeostasis after trauma is a major cause of post-traumatic organ dysfunction and/or sepsis. Recently, a variety of neutrophil phenotypes with distinct functions have been identified and suggested as involved in various clinical conditions. The association between neutrophil phenotypes and post-traumatic immunodeficiency has also been reported, yet the specific neutrophil phenotypes and their functional significance in post-traumatic sepsis have not been fully clarified. Therefore, we sought to investigate neutrophil phenotypic changes in a murine model, as these may hold prognostic value in post-traumatic sepsis.

Materials and methods

Third-degree burns affecting 25% of the body surface area were used to establish trauma model, and sepsis was induced 24 h later through cecal ligation and puncture (CLP). The Burn/CLP post-traumatic sepsis model and the Sham/CLP control model were established to assess the immunological status after trauma. Histopathological evaluation was performed on the spleen, liver, kidneys, and lung tissues. Immunological evaluation included the assessment of neutrophil markers using mass cytometry as well as cytokine measurements in serum and ascitic fluid through multiplex analysis using LUMINEX®.

Results

The Burn/CLP group had a lower survival rate than the Sham/CLP group. Histopathological examination revealed an impaired immune response and more advanced organ damage in the Burn/CLP group. Furthermore, the Burn/CLP group exhibited higher levels of transforming growth factor-beta 1 in the blood and generally lower levels of cytokines than the Sham/CLP group. CD11b, which is involved in neutrophil adhesion and migration, was highly expressed on neutrophils in the Burn/CLP group. The expression of CD172a, which is related to the inhibition of phagocytosis, was also upregulated on neutrophils in the Burn/CLP group. The expression of sialic acid-binding lg-like lectin F and CD68 also differed between the two groups.

Conclusion

Different neutrophil phenotypes were observed between Burn/CLP and Sham/CLP groups, suggesting that neutrophils are implicated in the immune imbalance following trauma. However, further studies are needed to prove the causal relationships between neutrophil phenotypes and outcomes, including survival rate and organ dysfunction.
Induction of protective interferon-β responses in murine osteoblasts following Staphylococcus aureus infection
Authors: Johnson M. Brittany , Furr Kelli H. , Suptela Samantha R. , Leach Whitney , Marriott Ian
Published: December 2022

Introduction

The refractory and recurrent nature of chronic staphylococcal osteomyelitis may be due, at least in part, to the ability of Staphylococcus aureus to invade and persist within bone-forming osteoblasts. However, osteoblasts are now recognized to respond to S. aureus infection and produce numerous immune mediators and bone regulatory factors that can shape the host response. Type I interferons (IFNs) are best known for their antiviral effects, but it is becoming apparent that they impact host susceptibility to a wide range of pathogens including S. aureus.

Methods

Here, we have assessed the local expression of IFN-β by specific capture ELISA in an established in vivo mouse model of staphylococcal osteomyelitis. RNA Tag-Seq analysis, specific capture ELISAs, and/or immunoblot analyses, were then used to assess the expression of type I IFNs and select IFN stimulated genes (ISGs) in S. aureus infected primary murine osteoblasts. The effect of IFN-β on intracellular S. aureus burden was assessed in vitro following recombinant cytokine treatment by serial colony counts of liberated bacteria.

Results

We report the presence of markedly elevated IFN-β levels in infected bone tissue in a mouse model of staphylococcal osteomyelitis. RNA Tag-Seq analysis of S. aureus infected osteoblasts showed enrichment of genes associated with type I IFN signaling and ISGs, and elevated expression of mRNA encoding IFN-β and ISG products. IFN-β production was confirmed with the demonstration that S. aureus induces its rapid and robust release by osteoblasts in a dose-dependent manner. Furthermore, we showed increased protein expression of the ISG products IFIT1 and IFIT3 by infected osteoblasts and demonstrate that this occurs secondary to the release of IFN-β by these cells. Finally, we have determined that exposure of S. aureus-infected osteoblasts to IFN-β markedly reduces the number of viable bacteria harbored by these cells.

Discussion

Together, these findings indicate an ability of osteoblasts to respond to bacteria by producing IFN-β that can act in an autocrine and/or paracrine manner to elicit ISG expression and mitigate S. aureus infection.