bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is red distribution width a valid tool to predict impaired iron transport in heart failure?
Authors: Campodonico Jeness , Carulli Ermes , Doni Francesco , Russo Gerardo Lo , Junod Daniele , Gaudenzi Asinelli Margherita , Bonomi Alice , De Martino Fabiana , Vignati Carlo , Pezzuto Beatrice , Agostoni Piergiuseppe 
Published: April 2023

BackgroundImpaired iron transport (IIT) is a form of iron deficiency (ID) defined as transferrin saturation (TSAT) &lt; 20% irrespective of serum ferritin levels. It is frequently observed in heart failure (HF) where it negatively affects prognosis irrespective of anaemia.ObjectivesIn this retrospective study we searched for a surrogate biomarker of IIT.MethodsWe tested the predictive power of red distribution width (RDW), mean corpuscular volume (MCV) and mean corpuscular haemoglobin concentration (MCHC) to detect IIT in 797 non-anaemic HF patients.ResultsAt ROC analysis, RDW provided the best AUC (0.6928). An RDW cut-off value of 14.2% identified patients with IIT, with positive and negative predictive values of 48 and 80%, respectively. Comparison between the true and false negative groups showed that estimated glomerular filtration rate (eGFR) was significantly higher (p = 0.0092) in the true negative vs. false negative group. Therefore, we divided the study population according to eGFR value: 109 patients with eGFR ≥ 90 ml/min/1.73 m2, 318 patients with eGFR 60–89 ml/min/1.73 m2, 308 patients with eGFR 30–59 ml/min/1.73 m2 and 62 patients with eGFR &lt; 30 ml/min/1.73 m2. In the first group, positive and negative predictive values were 48 and 81% respectively, 51 and 85% in the second group, 48 and 73% in the third group and 43 and 67% in the fourth group.ConclusionRDW may be seen as a reliable marker to exclude IIT in non-anaemic HF patients with eGFR ≥60 ml/min/1.73 m2.
Safety and efficacy of substance-based medical devices: Design of an in vitro barrier effect test
Authors: Bassetto Rebecca , Perin Stefano , Amadio Emanuele , Zanatta Samuele , Nenzioni Davide , Bertin Walter 
Published: April 2023

This study aims to develop an in vitro barrier effect test over biomimetic membrane, which is useful to establish the film forming ability of a substance-based medical device (SB-MD). The method contemplates a multiparametric approach including: i) the measurement of the transmembrane passage of a molecular-like marker over a lipid-impregnated biomimetic membrane (simulating the skin and gastro-intestinal and buccal tissues) by using a static diffusion cell apparatus (Franz cell); and ii) the evaluation of the integrity of the membrane (colorimetric test). In the first step, a series of lipid-impregnated biomimetic membranes (simulating gastro-intestinal, buccal, and skin tissues) were implemented and their permeability performance validated using model drugs (caffeine and acyclovir) by referring to literature data. As a result, the apparent permeability (Papp) of caffeine over the biomimetic gastro-intestinal membrane (Papp = 30.5E-6 cm/s) was roughly comparable to the literature values obtained with Caco-2 cell line membrane (Papp = 30.8E-6 cm/s) and with the Franz cell method (Papp = 36.2E-6 cm/s). Acyclovir was shown to be a poorly permeable substance both in the literature and experimental data. Following this step, the permeability study was extended to both biomimetic buccal and skin (STRAT-M®) membranes: for caffeine, biomimetic gastro-intestinal membrane was the most permeable (Papp = 30.5E-6 cm/s), followed by the buccal (Papp = 18.2E-6 cm/s) then the skin (Papp = 0.5E-6 cm/s) biomimetic membranes. In a second part of the work, the barrier effect test was developed following a similar permeability-like approach. The protocol was designed with the idea of assessing the capacity of a certain product to prevent the passage of caffeine across the biomimetic membrane with respect to a negative and positive control. The untreated membrane was the negative control, while membrane covered with a Vaseline film was the positive. As a last step, the developed barrier effect protocol was applied to an experimental gel-like SB-MD under development for the treatment of aphthae (Aphthae gel, an invented trade name), herein used as a case study. Regarding the results, Aphthae gel reduced the caffeine passage by 60.3%, thus highlighting its effectiveness to form a protective film. Overall, these results provide important knowledge and may pave the way for the use—including for industrial applications—of these simple but effective biomimetic membranes for carrying out high throughput screening necessary to design safe and effective SB-MDs before proceeding further with clinical trials, as requested by the regulations.
Characterization of the functional and transcriptomic effects of pro-inflammatory cytokines on human EndoC-βH5 beta cells
Authors: Frørup Caroline , Gerwig Rebekka , Svane Cecilie Amalie Søndergaard , Mendes Lopes de Melo Joana , Henriksen Kristine , Fløyel Tina , Pociot Flemming , Kaur Simranjeet , Størling Joachim 
Published: April 2023

ObjectiveEndoC-βH5 is a newly established human beta-cell model which may be superior to previous model systems. Exposure of beta cells to pro-inflammatory cytokines is widely used when studying immune-mediated beta-cell failure in type 1 diabetes. We therefore performed an in-depth characterization of the effects of cytokines on EndoC-βH5 cells.MethodsThe sensitivity profile of EndoC-βH5 cells to the toxic effects of interleukin-1β (IL-1β), interferon γ (IFNγ) and tumor necrosis factor-α (TNFα) was examined in titration and time-course experiments. Cell death was evaluated by caspase-3/7 activity, cytotoxicity, viability, TUNEL assay and immunoblotting. Activation of signaling pathways and major histocompatibility complex (MHC)-I expression were examined by immunoblotting, immunofluorescence, and real-time quantitative PCR (qPCR). Insulin and chemokine secretion were measured by ELISA and Meso Scale Discovery multiplexing electrochemiluminescence, respectively. Mitochondrial function was evaluated by extracellular flux technology. Global gene expression was characterized by stranded RNA sequencing.ResultsCytokines increased caspase-3/7 activity and cytotoxicity in EndoC-βH5 cells in a time- and dose-dependent manner. The proapoptotic effect of cytokines was primarily driven by IFNγ signal transduction. Cytokine exposure induced MHC-I expression and chemokine production and secretion. Further, cytokines caused impaired mitochondrial function and diminished glucose-stimulated insulin secretion. Finally, we report significant changes to the EndoC-βH5 transcriptome including upregulation of the human leukocyte antigen (HLA) genes, endoplasmic reticulum stress markers, and non-coding RNAs, in response to cytokines. Among the differentially expressed genes were several type 1 diabetes risk genes.ConclusionOur study provides detailed insight into the functional and transcriptomic effects of cytokines on EndoC-βH5 cells. This information should be useful for future studies using this novel beta-cell model.
Short-term effects of increasing compost application rates on soil C and greenhouse gas (N2O and CO2) emissions in a California central coast vineyard
Authors: Wong Connie T. F. , Falcone Mia , Rich Geovan , Stubler Craig , Malama Bwalya , Lazcano Cristina , Decock Charlotte 
Published: April 2023

Compost application is commonly considered by winegrape producers to improve soil health while sequestering carbon (C) and mitigating climate change. However, inputs of available C and nitrogen (N) as nutrients can induce emissions of greenhouse gases (GHG) such as carbon dioxide (CO2) and nitrous oxide (N2O). A 2-year field experiment in a Mediterranean vineyard on the California Central Coast was conducted to investigate the short-term effects of compost application at four different rates on soil C dynamics and greenhouse gas emissions. Two years of greenhouse gas sampling were performed using static chambers at vineyard management events in two functional locations (tractor row and under the vines). Soil samples were collected annually in spring at the same locations at 0–15, 15–30 and 30–60 cm depth, and during greenhouse gas sampling at 0–15 cm. The increasing compost application rate did not increase soil C stock, cumulative greenhouse gas emissions and global warming potential. The increase in active soil C observed to the depth of 60 cm suggests that increasing the compost application rate up to the rate of 13.5 Mg ha-1 year-1 can facilitate the early stages of C stabilization and sequestration. Compost application did not have a significant effect on grape yield or cover crop growth during the study. Our results provided important information on the potential environmental tradeoffs as greenhouse gas emissions from compost applications, which should be taken into account when considering the vineyard C budget.
Impact of COVID-19 and green finance on transportation energy carbon emissions in China: From the perspective of an automobile energy consumption structure
Authors: Liu Lingyun , Cheng Yanxin , Guan Ningning , Liu Yazhen , Zhang Xin , Li Yang , Yang Zining 
Published: April 2023

Background: In China, the transportation sector is the main energy consumer and the main source of carbon emissions. Reducing carbon emissions in the transportation sector is an important goal for China, especially during the current period of economic development. Due to the impact of pandemic shocks, the rapid development of green finance is conducive to supporting the transportation sector in achieving a carbon peak. Thus, we examined whether the development of green finance is still effective under the impact of a pandemic and the actual effect of green finance on the reduction of carbon emissions.Methods: In this study, we searched the internet for consumption structure data of vehicles and green finance indices of 30 Chinese provinces and cities from 2016 to 2021. A regression discontinuity model was constructed to test the effect of pandemic shock and green finance development on the reduction of transportation energy carbon emissions.Results: The results show that the impact of the COVID-19 pandemic has helped people change their preference toward more energy-efficient vehicles and reduce carbon emissions in the transportation sector. Green finance can effectively contribute to the reduction of transportation energy carbon emissions; however, the overall mitigation effect is limited.Conclusion: The empirical evidence is not only helpful in assessing the long-term impact of the COVID-19 pandemic but also conducive to the appropriate establishment of policy tools for supporting green finance development, which is further conducive to reducing carbon emissions in the transportation sector.
Soil C:N:P stoichiometry and its influencing factors in forest ecosystems in southern China
Authors: Lu Mengzhen , Zeng Fuping , Lv Siwei , Zhang Hao , Zeng Zhaoxia , Peng Wanxia , Song Tongqing , Wang Kelin , Du Hu 
Published: April 2023

IntroductionSoil carbon and nutrient contents and their stoichiometric characteristics play a vital role in indicating plant growth and element balance, which can be used to indicate nutrient limitation. However, it has been less studied about their driving factors within forest soils at the regional scale in southern China.MethodsIn this study, soil organic carbon (SOC), total nitrogen (TN), and total phosphorus (TP) were analyzed in the topsoil (0–10 cm) at 345 sampling plots representing different forest types in Guangxi Province.ResultsThe results showed that the mean contents of C, N, and P were 29.80, 2.46, and 0.51 g/kg, respectively, and soil C:N, C:P, and N:P were 13.95, 69.60, and 5.53 respectively. The ratios also showed remarkable correlations with each other. C, N, and P contents and their ratios presented significant differences among different soil and vegetation types. C, N, and P concentrations increased with the increase of elevation and latitude, and decrease with the increase of average annual temperature (MAT). Conversely, C:N showed an opposite trend. C, N, and N:P were also increased with increasing average annual precipitation (MAP). Collectively, soil type, vegetation type, geographical, and climatic factors explained 43.46, 64.02, 68.61, 32.93, 39.64, and 37.87% of the variance in C, N, P, C:N, C:P, and N:P, respectively. For Soil C, both latitude and MAP had strong influences. Soil type was the largest explanation for soil N and P contents. Latitude and longitude were the key factors determining the soil stoichiometric ratios.DiscussionOverall, soil type, geographical and climatic factors were the most vital explanation variables for soil nutrients and their stoichiometric ratios. These results could help improve our understanding of soil stoichiometry within forest ecosystems in southern China.
Applying amplification refractory mutation system technique to detecting cell-free fetal DNA for single-gene disorders purpose
Authors: Tan Yu , Jian Hui , Zhang Ranran , Wang Jing , Zhou Cong , Xiao Yuanyuan , Liang Weibo , Wang Li 
Published: April 2023

Non-invasive prenatal diagnosis for single-gene disorders (NIPD) is still in development and deserves further study. The advent of next-generation sequencing technology significantly improved the detection of multiple mutations for non-invasive prenatal diagnosis for single-gene disorder purposes. However, bespoke amplicon-based NGS assays are costly. In this study, we developed a new strategy for non-invasive prenatal screening for single-gene disorders based on a capillary electrophoresis (CE) platform using an amplification refractory mutation system (ARMS)-PCR technique. Allele-specific primers for several disease-correlated mutations were designed, and subsequently, sensitivity and specificity assays were conducted. Assays on simulated two-person DNA mixtures showed that three primers targeting the mutant allele could detect minor DNA components in 1:500 mixtures. All primers showed positive results at 0.01 ng of the template DNA. Cell-free fetal DNA was extracted from a pregnant woman’s peripheral blood for the detection of paternally inherited mutations. Our results showed that one primer successfully amplified the mutant allele of fetal DNA in maternal plasma, which was confirmed by genotyping the genomic DNA extracted from amniotic fluid. This study suggested that the ARMS-PCR technique, a fast and cost-effective method, might be a promising method used to target de novo or paternally inherited pathogenic mutations in maternal plasma.
Whole transcriptome sequencing reveals HOXD11-AGAP3, a novel fusion transcript in the Indian acute leukemia cohort
Authors: Desai Sagar Sanjiv , Ravindran Febina , Panchal Amey , Ojha Nishit , Jadhav Sachin , Choudhary Bibha 
Published: April 2023

Introduction: Acute leukemia is a heterogeneous disease with distinct genotypes and complex karyotypes leading to abnormal proliferation of hematopoietic cells. According to GLOBOCAN reports, Asia accounts for 48.6% of leukemia cases, and India reports ~10.2% of all leukemia cases worldwide. Previous studies have shown that the genetic landscape of AML in India is significantly different from that in the western population by WES.Methods: We have sequenced and analyzed 9 acute myeloid leukemia (AML) transcriptome samples in the present study. We performed fusion detection in all the samples and categorized the patients based on cytogenetic abnormalities, followed by a differential expression analysis and WGCNA analysis. Finally, Immune profiles were obtained using CIBERSORTx.Results: We found a novel fusion HOXD11-AGAP3 in 3 patients, BCR-ABL1 in 4, and KMT2A-MLLT3 in one patient. Categorizing the patients based on their cytogenetic abnormalities and performing a differential expression analysis, followed by WGCNA analysis, we observed that in the HOXD11-AGAP3 group, correlated co-expression modules were enriched with genes from pathways like Neutrophil degranulation, Innate Immune system, ECM degradation, and GTP hydrolysis. Additionally, we obtained HOXD11-AGAP3-specific overexpression of chemokines CCL28 and DOCK2. Immune profiling using CIBRSORTx revealed differences in the immune profiles across all the samples. We also observed HOXD11-AGAP3-specific elevated expression of lincRNA HOTAIRM1 and its interacting partner HOXA2.Discussion: The findings highlight population-specific HOXD11-AGAP3, a novel cytogenetic abnormality in AML. The fusion led to alterations in immune system represented by CCL28 and DOCK2 over-expression. Interestingly, in AML, CCL28 is known prognostic marker. Additionally, non-coding signatures (HOTAIRM1) were observed specific to the HOXD11-AGAP3 fusion transcript which are known to be implicated in AML.
Detection of HTLV-1 proviral DNA in cell-free DNA: Potential for non-invasive monitoring of Adult T cell leukaemia/lymphoma using liquid biopsy?
Authors: Joris Thomas , Haddow Jana , Taylor Graham P. , Cook Lucy B. M. , Rowan Aileen G. 
Published: April 2023

IntroductionFragmented genomic DNA is constitutively released from dying cells into interstitial fluid in healthy tissue. In cancer, this so-called ‘cell-free’ DNA (cfDNA) released from dying malignant cells encodes cancer-associated mutations. Thus, minimally invasive sampling of cfDNA in blood plasma can be used to diagnose, characterise and longitudinally monitor solid tumours at remote sites in the body. ~5% of carriers of Human T cell leukaemia virus type 1 (HTLV-1) develop Adult T cell leukaemia/lymphoma (ATL), and a similar percentage develop an inflammatory CNS disease, HTLV-1 associated myelopathy (HAM). In both ATL and HAM, high frequencies of HTLV-1 infected cells are present in the affected tissue: each carrying an integrated DNA copy of the provirus. We hypothesised that turnover of infected cells results in the release of HTLV-1 proviruses in cfDNA, and that analysis of cfDNA from infected cells in HTLV-1 carriers might contain clinically useful information pertaining to inaccessible sites in the body- e.g. for early detection of primary or relapsing localised lymphoma type ATL. To evaluate the feasibility of this approach, we tested for HTLV-1 proviruses in blood plasma cfDNA.MethodsCfDNA (from blood plasma) and genomic DNA (gDNA, from peripheral blood mononuclear cells, PBMC) was isolated from blood from 6 uninfected controls, 24 asymptomatic carriers (AC), 21 patients with HAM and 25 patients with ATL. Proviral (HTLV-1 Tax) and human genomic DNA (the beta globin gene, HBB) targets were quantified by qPCR using primer pairs optimised for fragmented DNA.ResultsPure, high quality cfDNA was successfully extracted from blood plasma of all study participants. When compared with uninfected controls, HTLV-1 carriers had higher concentrations of cfDNA circulating in their blood plasma. Patients with ATL who were not in remission had the highest levels of blood plasma cfDNA in any group studied. HTLV-1 proviral DNA was detected in 60/70 samples obtained from HTLV-1 carriers. The proviral load (percentage of cells carrying proviruses) was approximately tenfold lower in plasma cfDNA than in PBMC genomic DNA, and there was a strong correlation between the proviral load in cfDNA and PBMC genomic DNA in HTLV-1 carriers that did not have ATL. cfDNA samples in which proviruses were undetectable also had very low proviral load in PBMC genomic DNA. Finally, detection of proviruses in cfDNA of patients with ATL was predictive of clinical status: patients with evolving disease had higher than expected total amount of proviruses detectable in plasma cfDNA.DiscussionWe demonstrated that (1) HTLV-1 infection is associated with increased levels of blood plasma cfDNA, (2) proviral DNA is released into blood plasma cfDNA in HTLV-1 carriers and (3) proviral burden in cfDNA correlates with clinical status, raising the possibility of developing assays of cfDNA for clinical use in HTLV-1 carriers.
Biocompacting livestock accelerate drowning of tidal salt marshes with sea level rise
Authors: Elschot Kelly , Baptist Martin J. , van Puijenbroek Marinka E. B. 
Published: April 2023

A global concern for coastal ecosystems is the predicted rise in sea-level for which salt marshes must keep pace by increasing in surface elevation sufficiently. Variables that control this elevation change need to be identified to predict the adaptability of marshes to future sea-level rise. Many European marshes are grazed by livestock and these heavy grazers can biocompact the soil, a process often underestimated in studies assessing the long-term survival of marshes. We measured elevation changes for thirteen years in the field in grazed and non-grazed marshes. With a statistical model the most important factors controlling rates of surface elevation change were identified and provided the input for a mathematical model to study future elevation change of grazed and non-grazed salt marshes up to 2100 under three Sea Level Rise and sediment supply scenarios. We found that trampling by grazing cattle significantly reduced the annual rates of elevation gain from 11.9 mm yr-1 in the non-grazed marsh to 3.6 mm yr-1 in the grazed marsh. Next to biocompaction by livestock, precipitation deficit and extreme drought resulted in extra compaction. Our model results showed that cattle presence had a negative impact on the future adaptability of salt marshes to grow vertically for rising sea levels. Biocompaction reduced the total elevation change by 42% if the current linear SLR does not accelerate. For an accelerating and high SLR to 109 cm +NAP in 2100, biocompaction reduced elevation changes by 12% and the grazed marsh can no longer outcompete the rise in sea level from around 2050 onwards, compared to the non-grazed marsh. The grazed marsh will slowly drown but this will not lead to a significant change in vegetation composition yet. For an extreme SLR to 195 cm +NAP in 2100 the elevation changes in both the grazed and non-grazed marshes cannot keep pace with the rise in sea level and the marsh vegetation is expected to show regression to plants typical for a low marsh. A reduction in sediment supply will aggravate the effects of SLR and may result in highly increasing inundation frequencies and subsequent disappearance of the marsh vegetation.
The transcriptome of Litopenaeus vannamei in zoea larvae and adults infected by Vibrio parahaemolyticus
Authors: Chen Nanxiong , Jin Jiaojiao , Chen Yibin , Hu Yicheng , Shen Yuchun , Li Sedong 
Published: April 2023

IntroductionThe rapid development of the Litopenaeus vannamei industry largely depends on the acquisition of high-quality larvae. Shrimp larval development is a unique metamorphic process that results in mortality due to disease vulnerability. Currently, studies on innate immunity in shrimp are mainly focused on the adult stage, but little has been done on innate immunity in larvae.MethodsIn this study, utilizing a high-throughput Illumina sequencing approach, we compare the transcriptome of L. vannamei Zoea larvae and adults infected by Vibrio parahaemolyticus.ResultsA total of 487,887,650 high quality reads were obtained, assembled, and aggregated into 23,802 genes, among which 3315 were identified as differentially expressed genes. Then GO term enrichment analysis, KEGG pathway enrichment analysis and functional gene analysis were performed. We found that pathways that are involved in the innate immune response, such as mTOR signaling pathway, MAPK signaling pathway, and Notch signaling pathway, were more enriched in the Zoea stage compared to the adult stage, suggesting that innate immunity against Vibrio vulnificus may exist during the Zoea larvae stage.Discussionwere more enriched in the Zoea stage compared to the adult stage, suggesting that innate immunity against Vibrio vulnificus may exist during the Zoea larvae stage. These findings will provide useful information for the study of innate immunity in shrimp larvae.