bluuebunny/crossref_metadata_2025 huggingface dataset:
A Retrospective Analysis of Chemical Constituents in Regulated and Unregulated E-Cigarette Liquids
Authors: Holt Alaina K. , Poklis Justin L. , Peace Michelle R.
Published: October 2021

E-cigarette or vaping use-associated lung injury (EVALI) was identified with the incidents of a multi-state outbreak of acute lung injuries associated with the use of electronic cigarettes (e-cigs) and attributed to vitamin E acetate in off-market cannabis-based e-liquids. Aside from EVALI, hypersecretion of mucus, irritated nasal passages, and watery, red eyes have been defined as complaints associated with vaping standard nicotine-based e-liquids. The chemical composition of e-liquids varies between manufacturers and robust oversight of ingredients is lacking. Manufacturers use chemicals deemed “generally recognized as safe” (GRAS) by the FDA, a designation for chemicals used in foodstuffs to be ingested. Most “GRAS” chemicals are associated with at least one Global Harmonization System (GHS) warning class, ranging from irritant to toxic. Untargeted chemical analysis is critical to evaluate e-liquid products to determine chemical composition; equally important is the quantitation of components to help elucidate the potential harms from exceeding recommended exposure limits. Untargeted screening of e-liquids was accomplished using gas chromatography-mass spectrometry (GC-MS) and Direct Analysis in Real Time-AccuTOF™ mass spectrometry (DART-ToF-MS) and has identified 350 chemical constituents from 241 products analyzed. Nicotine, caffeine, menthol, and vitamin E were confirmed and quantitated by GC-MS, ethanol was confirmed and quantitated by headspace-gas chromatography-dual flame ionization detection (HS-GC-FID), and olivetol and cannabinoids were confirmed and quantitated by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Maximum identified concentrations of nicotine, caffeine, menthol, vitamin E, ethanol, olivetol, Δ9-tetrahydrocannabinol, and cannabidiol were 56.4, 26.9, 4.28, 307.9, 217.2, 399.6, 497.7, and 332.6 mg/ml, respectively. Evaluation of untargeted analysis and quantitation of unlabeled chemical components of e-liquids is essential to improving etiology of acute lung injury and less severe impacts of vaping, both short-term and long-term. The historical documentation of unlabeled ingredients can provide some insight for a retrospective analysis of health consequences and inform policy discussions.
Observation of the Gut Microbiota Profile in C57BL/6 Mice Induced by Plasmodium berghei ANKA Infection
Authors: Guan Wei , Yang Shuguo , Zhao Yanqing , Cheng Weijia , Song Xiaonan , Yao Yi , Xie Yiting , Du Weixing , Li Jian
Published: October 2021

The genus of Plasmodium parasites can cause malaria, which is a prevalent infectious disease worldwide, especially in tropical and subtropical regions. C57BL/6 mice infected with P. berghei ANKA (PbA) will suffer from experimental cerebral malaria (ECM). However, the gut microbiota in C57BL/6 mice has rarely been investigated, especially regarding changes in the intestinal environment caused by infectious parasites. P. berghei ANKA-infected (PbA group) and uninfected C57BL/6 (Ctrl group) mice were used in this study. C57BL/6 mice were infected with PbA via intraperitoneal injection of 1 × 106 infected red blood cells. Fecal samples of two groups were collected. The microbiota of feces obtained from both uninfected and infected mice was characterized by targeting the V4 region of the 16S rRNA through the Illumina MiSeq platform. The variations in the total gut microbiota composition were determined based on alpha and beta diversity analyses of 16S rRNA sequencing. The raw sequences from all samples were generated and clustered using ≥ 97% sequence identity into many microbial operational taxonomic units (OTUs). The typical microbiota composition in the gut was dominated by Bacteroidetes, Firmicutes, Proteobacteria, and Verrucomicrobia at the phylum level. Bacteroidetes and Verrucomicrobia were considerably decreased after PbA infection compared with the control group (Ctrl), while Firmicutes and Proteobacteria were increased substantially after PbA infection compared with Ctrl. The alpha diversity index showed that the observed OTU number was increased in the PbA group compared with the Ctrl group. Moreover, the discreteness of the beta diversity revealed that the PbA group samples had a higher number of OTUs than the Ctrl group. LEfSe analysis revealed that several potential bacterial biomarkers were clearly related to the PbA-infected mice at the phylogenetic level. Several bacterial genera, such as Acinetobacter, Lactobacillus, and Lachnospiraceae_NK4A136_group, were overrepresented in the PbA-infected fecal microbiota. Meanwhile, a method similar to gene coexpression network construction was used to generate the OTU co-abundance units. These results indicated that P. berghei ANKA infection could alter the gut microbiota composition of C57BL/6 mice. In addition, potential biomarkers should offer insight into malaria pathogenesis and antimalarial drug and malaria vaccine studies.
Gut Microbiota, Glucose, Lipid, and Water-Electrolyte Metabolism in Children With Nonalcoholic Fatty Liver Disease
Authors: Pan Xiongfeng , Kaminga Atipatsa C. , Liu Aizhong , Wen Shi Wu , Luo Miyang , Luo Jiayou
Published: October 2021

There is evidence that nonalcoholic fatty liver disease (NAFLD) is affected by gut microbiota, glucose, and lipid. However, the function of water-electrolyte metabolism remains undefined in children with NAFLD. Therefore, the aim of this case-control study was to better understand these interactions. The sample consisted of 75 children, aged between 7 and 16, of whom 25 had nonalcoholic fatty liver (NAFL), 25 had nonalcoholic steatohepatitis (NASH), and 25 were obese and without NAFLD. These groups were matched by age, sex, and body mass index. Data were collected between June, 2019 and December, 2019 at the Hunan Children’s Hospital, in China. Microbiome composition in fecal samples was assessed using 16S ribosomal RNA amplicon sequencing. In the clinical indices, 12 glucose and lipid metabolism indices were included, and six water-electrolyte metabolism indices were included. The results indicated that microbiomes of NAFLD children had lower alpha diversity but higher beta diversity index than the other two groups. Specifically, anti-inflammatory and probiotics abundance (e.g., Faecalibacterium, Akkermansia, and Bifidobacterium_adolescentis) was significantly decreased in NAFLD, whereas the abundance of harmful bacteria (e.g., Staphylococcaceae) was increased. Moreover, the abundance of butyrate-producing bacteria (e.g., Faecalibacterium, Roseburia_inulinivorans, Roseburia_intestinalis, and Coprococcus_comes) was significantly decreased in NASH. The abundance of these bacteria were associated with glucose, lipid, and water-electrolyte metabolism (e.g., glucose, triglyceride, cholesterol, inorganic salt, total body water, etc.), implying that the NAFLD and its severity were associated with glucose, lipid, and water-electrolyte metabolism dysbiosis. Therefore, these findings suggest that the gut microbiome, especially butyrate-producing bacteria, play an important role in the development of NAFLD in children.
Sesamol Induces Apoptosis-Like Cell Death in Leishmania donovani
Authors: Ali Rahat , Tabrez Shams , Akand Sajjadul Kadir , Rahman Fazlur , Husein Atahar , Arish Mohd , Alqahtani Ali S. , Ahmed Mohammad Z. , Husain Mohammad , Rub Abdur
Published: October 2021

Background

Visceral leishmaniasis (VL), caused by the protozoan parasite Leishmania donovani (L. donovani), is the most severe form of leishmaniasis. It is largely responsible for significant morbidity and mortality in tropical and subtropical countries. Currently, available therapeutics have lots of limitations including high-cost, adverse side-effects, painful route of administration, less efficacy, and resistance. Therefore, it is time to search for cheap and effective antileishmanial agents. In the present work, we evaluated the antileishmanial potential of sesamol against promastigotes as well as intracellular amastigotes. Further, we tried to work out its mechanism of antileishmanial action on parasites through different assays.

Methodology

In vitro and ex vivo antileishmanial assays were performed to evaluate the antileishmanial potential of sesamol on L. donovani. Cytotoxicity was determined by MTT assay on human THP-1-derived macrophages. Sesamol-induced morphological and ultrastructural changes were determined by electron microscopy. H2DCFDA staining, JC-1dye staining, and MitoSOX red staining were performed for reactive oxygen assay (ROS), mitochondrial membrane potential, and mitochondrial superoxide, respectively. Annexin V/PI staining for apoptosis, TUNEL assay, and DNA laddering for studying sesamol-induced DNA fragmentation were performed.

Conclusions

Sesamol inhibited the growth and proliferation of L. donovani promastigotes in a dose-dependent manner. It also reduced the intracellular parasite load without causing significant toxicity on host-macrophages. Overall, it showed antileishmanial effects through induction of ROS, mitochondrial dysfunction, DNA fragmentation, cell cycle arrest, and apoptosis-like cell death to parasites. Our results suggested the possible use of sesamol for the treatment of leishmaniasis after further in vivo validations.
Molecular Epidemiology of Extraintestinal Pathogenic Escherichia coli Causing Hemorrhagic Pneumonia in Mink in Northern China
Authors: Yu Ying , Hu Bo , Fan Huanhuan , Zhang Hailing , Lian Shizhen , Li Hongye , Li Shuangshuang , Yan Xijun , Wang Shaohui , Bai Xue
Published: October 2021

The molecular epidemiology and biological characteristics of Escherichia coli associated with hemorrhagic pneumonia (HP) mink from five Chinese Provinces were determined. From 2017 to 2019, 85 E. coli strains were identified from 115 lung samples of mink suffering from HP. These samples were subjected to serotyping, antimicrobial susceptibility, detection of virulence genes, phylogenetic grouping, whole-genome sequencing, drug resistant gene, multilocus sequence typing (MLST) and biofilm-forming assays. E. coli strains were divided into 18 serotypes. Thirty-nine E. coli strains belonged to the O11 serotype. Eighty-five E. coli strains were classified into seven phylogenetic groups: E (45.9%, 39/85), A (27.1%, 23/85), B1 (14.1%, 12/85), B2 (3.7%, 3/85), D (3.7%, 3/85), F (2.4%, 2/85) and clade I (1.2%, 1/85). MLST showed that the main sequence types (STs) were ST457 (27/66), All E. coli strains had ≥4 virulence genes. The prevalence of virulence was 98.8% for yijp and fimC, 96.5% for iucD, 95.3% for ompA, 91.8% for cnf-Ⅰ, 89.4% for mat, 82.3% for hlyF, and 81.2% for ibeB. The prevalence of virulence genes iss, cva/cvi, aatA, ibeA, vat, hlyF, and STa was 3.5–57.6%. All E. coli strains were sensitive to sulfamethoxazole, but high resistance was shown to tetracycline (76.5%), chloramphenicol (71.8%), ciprofloxacin (63.5%) and florfenicol (52.9%), resistance to other antibiotics was 35.3–16.5%. The types and ratios of drug-resistance genes were tet(A), strA, strB, sul2, oqxA, blaTEM-1B, floR, and catA1 had the highest frequency from 34%-65%, which were consistent with our drug resistance phenotype tetracycline, florfenicol, quinolones, chloramphenicol, the bla-NDM-I and mcr-I were presented in ST457 strains. Out of 85 E. coli strains, six (7.1%) possessed a strong ability, 12 (14.1%) possessed a moderate ability, and 64 (75.3%) showed a weak ability to form biofilm. Our data will aid understanding of the epidemiological background and provide a clinical basis for HP treatment in mink caused by E. coli.
A Framework for Operationalizing Climate-Just Ocean Commitments Under the Paris Agreement
Authors: Reiter Sarah M. , Cheng Laura M. , Pouponneau Angelique , Taylor Sophie , Wedding Lisa M.
Published: October 2021

Building on the considerable momentum from the commencement of the Decade of Ocean Science, the Ocean-climate nexus will be center stage at COP26. Many countries are including blue carbon Ocean commitments in their second round of nationally determined contributions (NDCs), and there is a need to harmonize the science, law, and economics of Ocean-based climate mitigation and adaptation strategies to enable implementation of Ocean commitments under the Paris Agreement. In addition, consistent with the Paris Agreement preamble's focus on human rights, the rights and empowerment of vulnerable and marginalized communities, and intergenerational equity, the design and implementation of Ocean commitments in NDCs should be centered on considerations of climate justice (“climate-just Ocean commitments”). The challenges and opportunities inherent in implementing climate-just Ocean commitments require a comprehensive review of the latest innovations in blue carbon scientific research, the enabling conditions necessary for uptake of this science into policies and decision making, and the financial structures needed to equitably finance Ocean nature-based solutions. Responding to this need, we propose that a framework is needed to support the inclusion of blue carbon sequestration potential in ambitious national and subnational action. The proposed framework should center on the intersectionality of climate justice with the three key layers essential to implementation of Ocean commitments—science, law, and economics—where traditional and local ecological knowledge is valued on par with western science, law and policy centers on vulnerable communities, and financial mechanisms respect national sovereignty, value local cultures, and support sustainable economic development.
COVID-19: The Cause of the Manifested Cardiovascular Complications During the Pandemic
Authors: Bandopadhyay Audditiya , Singh Alok Kumar , Chaubey Gyaneshwer
Published: October 2021

In the course of human history, we encountered several devastating waves of pandemics, affecting millions of lives globally and now the rapid and progressive spread of the novel SARS-CoV-2, causing Coronavirus disease (COVID-19) has created a worldwide wave of crisis. Profoundly straining national health care systems, it also significantly impacted the global economic stability. With the introduction of COVID-19 measures, mainly driven by immunization drives, casualties due to the virus were reported to decrease considerably. But then comes into play the post-Covid morbidities, along with their short and long-term effects on the elderly and the co-morbid population. Moreover, the pediatric population and the otherwise healthy cohort of the young athletes were also reported being largely affected by the varying amount of post-recovery virus-induced Cardiac manifestations, in the subsequent waves of the pandemic. Therefore, here we thrived to find answers to the seemingly unending series of questions that popped up with the advent of the disease, nevertheless, there still lies a blind spot in understanding the impacts of the disease on the Cardiovascular Health of an individual, even after the clinical recovery. Thus, along with the current data related to the diverse cardiovascular complications due to SARS-COV-2 infection, we suggest long-term ‘Cardiac surveillance' for the COVID-19 recovered individuals.
High-Intensity Statin vs. Low-Density Lipoprotein Cholesterol Target for Patients Undergoing Percutaneous Coronary Intervention: Insights From a Territory-Wide Cohort Study in Hong Kong
Authors: Ng Andrew Kei-Yan , Ng Pauline Yeung , Ip April , Siu Chung-Wah
Published: October 2021

Background: Different guidelines recommend different approaches to lipid management in patients with atherosclerotic cardiovascular disease. We aim to determine the best strategy for lipid management in Asian patients undergoing percutaneous coronary intervention (PCI).

Method: This was a retrospective cohort study conducted in patients who underwent first-ever PCI from 14 hospitals in Hong Kong. All participants either achieved low-density lipoprotein cholesterol (LDL-C) target of <55 mg/dl with ≥50% reduction from baseline (group 1), or received high-intensity statin (group 2), or both (group 3) within 1 yr after PCI. The primary endpoint was a composite outcome of all-cause mortality, myocardial infarction, stroke, and any unplanned coronary revascularization between 1 and 5 yr after PCI.

Results: A total of 8,650 patients were analyzed with a median follow-up period of 4.2 yr. After the adjustment of baseline characteristics, complexity of PCI and medications prescribed and the risks of the primary outcome were significantly lower in group 2 (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.74–0.93, P = 0.003) and group 3 (HR, 0.75; 95% CI, 0.62–0.90; P = 0.002). The primary outcome occurred at similar rates between group 2 and group 3.

Conclusions: Use of high intensity statin, with or without the attainment of guidelines recommended LDL-C target, was associated with a lower adjusted risk of MACE at 5 yr, compared with patients who attained LDL-C target without high intensity statin.
Impacts of Cigarette Smoking Status on Metabolomic and Gut Microbiota Profile in Male Patients With Coronary Artery Disease: A Multi-Omics Study
Authors: Hu Xiaomin , Fan Yue , Li Hanyu , Zhou Ruilin , Zhao Xinyue , Sun Yueshen , Zhang Shuyang
Published: October 2021

Background: Cigarette smoking has been considered a modifiable risk factor for coronary artery disease (CAD). Changes in gut microbiota and microbe-derived metabolites have been shown to influence atherosclerotic pathogenesis. However, the effect of cigarette smoking on the gut microbiome and serum metabolites in CAD remains unclear.

Method: We profiled the gut microbiota and serum metabolites of 113 male participants with diagnosed CAD including 46 current smokers, 34 former smokers, and 33 never smokers by 16S ribosomal RNA (rRNA) gene sequencing and untargeted metabolomics study. A follow-up study was conducted. PICRUSt2 was used for metagenomic functional prediction of important bacterial taxa.

Results: In the analysis of the microbial composition, the current smokers were characterized with depleted Bifidobacterium catenulatum, Akkermansia muciniphila, and enriched Enterococcus faecium, Haemophilus parainfluenzae compared with the former and never smokers. In the untargeted serum metabolomic study, we observed and annotated 304 discriminant metabolites, uniquely including ceramides, acyl carnitines, and glycerophospholipids. Pathway analysis revealed a significantly changed sphingolipids metabolism related to cigarette smoking. However, the change of the majority of the discriminant metabolites is possibly reversible after smoking cessation. While performing PICRUSt2 metagenomic prediction, several key enzymes (wbpA, nadM) were identified to possibly explain the cross talk between gut microbiota and metabolomic changes associated with smoking. Moreover, the multi-omics analysis revealed that specific changes in bacterial taxa were associated with disease severity or outcomes by mediating metabolites such as glycerophospholipids.

Conclusions: Our results indicated that both the gut microbiota composition and metabolomic profile of current smokers are different from that of never smokers. The present study may provide new insights into understanding the heterogenic influences of cigarette smoking on atherosclerotic pathogenesis by modulating gut microbiota as well as circulating metabolites.
Types and Micromorphology of Authigenic Carbonates in the Kolyma Yedoma Ice Complex, Northeast Siberia
Authors: Rogov Victor V. , Kurchatova Anna N. , Taratunina Natalia A.
Published: October 2021

The study focuses on authigenic carbonates that are widespread in different deposition environments and are a component part of the terrestrial biogeochemical cycle of carbon. Samples from the Kolyma Yedoma Ice Complex that formed during the Sartan Cryochrone (MIS 2), the coldest period of the Late Pleistocene, in the northeastern Siberian lowlands, have been studied utilizing scanning electron microscopy and energy-dispersive spectroscopy with replica technique. The samples bear signatures of irreversible multistage cryogenic changes in structure and composition, with the formation of authigenic minerals. Authigenic carbonates as secondary phases in the Ice Complex deposits are remarkable by local changes in chemical, physical, and other properties, which induce gradual changes in the lattice and conversion of one mineral species to another. As a result, the sediments may contain stable and metastable minerals. Crystalline species like calcite or aragonite precipitate from aqueous solutions and their presence are restricted to free pore space in segregation ice. Metastable phases may be produced as an initial reaction product between the CO2 and the aqueous phase, while mineral surfaces and small pores act as possible nucleation sites. Organic matter is also an important agent in the cryometamorphism of sediments, including precipitation of authigenic phases due to the freezing of colloids and high-molecular compounds.
Circum-Arctic Map of the Yedoma Permafrost Domain
Authors: Strauss Jens , Laboor Sebastian , Schirrmeister Lutz , Fedorov Alexander N. , Fortier Daniel , Froese Duane , Fuchs Matthias , Günther Frank , Grigoriev Mikhail , Harden Jennifer , Hugelius Gustaf , Jongejans Loeka L. , Kanevskiy Mikhail , Kholodov Alexander , Kunitsky Viktor , Kraev Gleb , Lozhkin Anatoly , Rivkina Elizaveta , Shur Yuri , Siegert Christine , Spektor Valentin , Streletskaya Irina , Ulrich Mathias , Vartanyan Sergey , Veremeeva Alexandra , Anthony Katey Walter , Wetterich Sebastian , Zimov Nikita , Grosse Guido
Published: October 2021

Ice-rich permafrost in the circum-Arctic and sub-Arctic (hereafter pan-Arctic), such as late Pleistocene Yedoma, are especially prone to degradation due to climate change or human activity. When Yedoma deposits thaw, large amounts of frozen organic matter and biogeochemically relevant elements return into current biogeochemical cycles. This mobilization of elements has local and global implications: increased thaw in thermokarst or thermal erosion settings enhances greenhouse gas fluxes from permafrost regions. In addition, this ice-rich ground is of special concern for infrastructure stability as the terrain surface settles along with thawing. Finally, understanding the distribution of the Yedoma domain area provides a window into the Pleistocene past and allows reconstruction of Ice Age environmental conditions and past mammoth-steppe landscapes. Therefore, a detailed assessment of the current pan-Arctic Yedoma coverage is of importance to estimate its potential contribution to permafrost-climate feedbacks, assess infrastructure vulnerabilities, and understand past environmental and permafrost dynamics. Building on previous mapping efforts, the objective of this paper is to compile the first digital pan-Arctic Yedoma map and spatial database of Yedoma coverage. Therefore, we 1) synthesized, analyzed, and digitized geological and stratigraphical maps allowing identification of Yedoma occurrence at all available scales, and 2) compiled field data and expert knowledge for creating Yedoma map confidence classes. We used GIS-techniques to vectorize maps and harmonize site information based on expert knowledge. We included a range of attributes for Yedoma areas based on lithological and stratigraphic information from the source maps and assigned three different confidence levels of the presence of Yedoma (confirmed, likely, or uncertain). Using a spatial buffer of 20 km around mapped Yedoma occurrences, we derived an extent of the Yedoma domain. Our result is a vector-based map of the current pan-Arctic Yedoma domain that covers approximately 2,587,000 km2, whereas Yedoma deposits are found within 480,000 km2of this region. We estimate that 35% of the total Yedoma area today is located in the tundra zone, and 65% in the taiga zone. With this Yedoma mapping, we outlined the substantial spatial extent of late Pleistocene Yedoma deposits and created a unique pan-Arctic dataset including confidence estimates.
Case Report: Successful Outcome for Refractory Diabetic Peripheral Neuropathy in Patients With Ultrasound-Guided Injection Treatment
Authors: Hu Hua Qiong , Huang Hailun , Huang Jing , Leng Ji Cui , Li Mi , Tang Chao , Li Yan , Wu Shan
Published: October 2021

Diabetic peripheral neuropathy is the most prevalent chronic complication of diabetes and is based on sensory and autonomic nerve symptoms. Generally, intensive glucose control and nerve nourishment are the main treatments. However, it is difficult to improve the symptoms for some patients; such cases are defined as refractory diabetic peripheral neuropathy (RDPN). In this paper, we present five patients treated with saline and mecobalamin by ultrasound-guided injection. The Visual Analog Scale and Toronto Clinical Scoring System were used to evaluate the symptoms, and the neuro-ultrasound scoring system and electrophysiological severity scale were evaluated by ultrasound and electrophysiological examination. In brief, ultrasound-guided hydrodissection may be a safe way to treat RDPN.
Hydrological Modeling for Multifunctional Landscape Planning in the Orinoquia Region of Colombia
Authors: Pimentel Jonathan Nogales , Rogéliz Prada Carlos Andres , Walschburger Thomas
Published: October 2021

With over 200,000 km2of natural savannas, the Orinoquia region of Colombia is a key and strategic conservation area. Because of Colombia’s fast economic growth, there are significant plans for agro-industrial expansion in the Orinoquia. This expansion may seriously affect water availability. To evaluate the cumulative impacts on freshwater ecosystems derived by different expansion scenarios, the use of a comprehensive framework for mathematical modeling, able to represent the hydrological processes at a macro-basin scale, is crucial for analysis and as a tool to bridge the gap between science and practice. In this work, we developed a general methodological framework for hydrological analysis at macro-basin scale consisting of four main stages: 1) collection and processing of hydro-climatological data, 2) characterization of hydro dependent water use sectors, 3) mathematical modeling and 4) scenario simulation. As a result of applying the proposed framework, we obtained a coupled hydrological model, which allows us to represent the rain-runoff process, the river-floodplain interaction and anthropic processes such as surface water extraction and groundwater extraction, enabling us to represent the complexity of the Orinoquia region. The model was successfully implemented in Matlab showing a Nash-Sutcliffe efficiency coefficient between 0.62 and 0.92 in calibration and between 0.49 and 0.92 in validation. With this model we analyzed five different agro-industrial expansion scenarios, finding that the Colombian Orinoquia may have future high pressure on water resource areas with critical changes in the water availability regime. The scenarios show reductions of up to 85% in low water flows in more than 50% of the area of the Colombian Orinoco basin. In the most extreme scenarios, the Meta, Vichada and Guaviare rivers show reductions of 95, 98 and 50% in low water flows. The results show an urgent need to consider hydrology in planning processes to ensure the sustainability of this important area in Colombia.
The Role of Intra-Clutch Variation of Magpie Clutches in Foreign Egg Rejection Depends on the Egg Trait Considered
Authors: Molina-Morales Mercedes , Gómez Jesús , Liñán-Cembrano Gustavo , Precioso Marta , Martínez Juan G. , Avilés Jesús M.
Published: October 2021

The existence of a coevolutionary process between avian brood parasites and their hosts predicts a lower intra-clutch variation in egg appearance of host eggs among rejecters as this would favor egg discrimination of parasite eggs by hosts once parasitic egg mimicry had evolved. So far empirical tests of this prediction have ignored the fact that different aspects of host egg phenotypes may differ in the relative role of environmental vs. genetic determination, and hence that the role of intra-clutch variation in egg rejection within a population cannot be invariant. Here, we estimated whether the intra-clutch variation in several aspects of host eggshell features is consistently associated to rejection of parasitic foreign eggs across years in a magpie host population parasitized by great spotted cuckoos. We innovatively estimated spottiness by means of the fractal dimension of eggs, which considers the homogeneity of spot pattern complexity in eggshells. Our results show that low intra-clutch variation in the blue-green coloration at the middle area of the eggs associated with a high chance of rejection, but only in one of the 3 years we conducted the study. In addition, females that rejected foreign eggs presented more homogenous spot patterns in their clutches as estimated by their fractal dimension than females that accepted experimental eggs, independently of the year of study. Finally, intra-clutch variation in egg volume of host eggs was not associated to rejection. Analyses at the individual level revealed that the relative role of genetic vs. environmental factors that determine egg phenotype would be feature-specific in magpies, females having a characteristic spottiness, but not color or volume, pattern. Our work stresses the importance of considering a holistic approach including several aspects of variation in host egg phenotype (size, color, and homogeneity of spot pattern), as some aspects might be more susceptible to selection through egg rejection than others, presumably because they are less influenced by variation in the environmental conditions. Moreover, our study highlights the importance of replication in studies on the adaptive value of host traits in egg rejection.
Whole-Genome SNP Characterisation Provides Insight for Sustainable Use of Local South African Livestock Populations
Authors: van Marle-Köster Esté , Lashmar Simon Frederick , Retief Anel , Visser Carina
Published: October 2021

Local cattle and sheep populations are important for animal production and food security in South Africa. These genetic resources are well adapted to the diverse climatic conditions and hold potential to be utilized in production systems subjected to climate change. The local beef breeds are well integrated into commercial livestock production systems with access to performance recording and genetic evaluations, while local sheep breeds are mainly utilised in smallholder and communal systems. The GeneSeek® Genomic Profiler™ Bovine 150 K SNP genotyping array was used to evaluate the diversity and inbreeding status of four indigenous (Boran, Drakensberger, Nguni, Tuli), two composite (Bonsmara and Beefmaster) and two exotic (SA Hereford and Charolais) beef breeds. The Illumina® Ovine 50 K SNP BeadChip was used to investigate five indigenous (Black Head Persian, Damara, Fat tail, Namaqua Afrikaner, Pedi) and three commercial (Dorper, Dohne Merino and SA Merino) populations. Although ascertainment bias was indicated by the low MAF (the autosome-wide proportion of SNPs with MAF< 0.05 ranged from 6.18 to 9.97% for cattle, and 7.59–13.81% for sheep), moderate genomic diversity was observed (mean Ho ranged from 0.296 to 0.403 for cattle, and 0.327 to 0.367 for sheep). Slightly higher levels of ROH-based inbreeding were calculated for cattle (FROH range: 0.018–0.104), than for sheep populations (FROH range: 0.002–0.031). The abundance of short ROH fragments (mean proportion of <4 Mb fragments: 0.405 for cattle, and 0.794 for sheep) indicated ancient inbreeding in both species. The eight cattle populations were categorized into indicine, taurine or Sanga subspecies based on principal component, model-based clustering and phylogenetic analyses, with high levels of admixture observed within the Drakensberger, Nguni and Tuli breeds. Within the sheep populations, a clear distinction could be seen between the dual-purpose breeds, the meat breed and the indigenous breeds. Despite directional selection practiced in the cattle breeds, genomic diversity was moderate with low inbreeding. The non-commercialized, indigenous sheep populations are more vulnerable with small effective populations. These results emphasise the value of genomic information for effective management to exploit the potential contribution of local genetic cattle and sheep resources in a changing environment.
Identifying miRNA-mRNA Networks Associated With COPD Phenotypes
Authors: Zhuang Yonghua , Hobbs Brian D , Hersh Craig P , Kechris Katerina
Published: October 2021

Chronic obstructive pulmonary disease (COPD) is characterized by expiratory airflow limitation and symptoms such as shortness of breath. Although many studies have demonstrated dysregulated microRNA (miRNA) and gene (mRNA) expression in the pathogenesis of COPD, how miRNAs and mRNAs systematically interact and contribute to COPD development is still not clear. To gain a deeper understanding of the gene regulatory network underlying COPD pathogenesis, we used Sparse Multiple Canonical Correlation Network (SmCCNet) to integrate whole blood miRNA and RNA-sequencing data from 404 participants in the COPDGene study to identify novel miRNA–mRNA networks associated with COPD-related phenotypes including lung function and emphysema. We hypothesized that phenotype-directed interpretable miRNA–mRNA networks from SmCCNet would assist in the discovery of novel biomarkers that traditional single biomarker discovery methods (such as differential expression) might fail to discover. Additionally, we investigated whether adjusting -omics and clinical phenotypes data for covariates prior to integration would increase the statistical power for network identification. Our study demonstrated that partial covariate adjustment for age, sex, race, and CT scanner model (in the quantitative emphysema networks) improved network identification when compared with no covariate adjustment. However, further adjustment for current smoking status and relative white blood cell (WBC) proportions sometimes weakened the power for identifying lung function and emphysema networks, a phenomenon which may be due to the correlation of smoking status and WBC counts with the COPD-related phenotypes. With partial covariate adjustment, we found six miRNA–mRNA networks associated with COPD-related phenotypes. One network consists of 2 miRNAs and 28 mRNAs which had a 0.33 correlation (p = 5.40E-12) to forced expiratory volume in 1 s (FEV1) percent predicted. We also found a network of 5 miRNAs and 81 mRNAs that had a 0.45 correlation (p = 8.80E-22) to percent emphysema. The miRNA–mRNA networks associated with COPD traits provide a systems view of COPD pathogenesis and complements biomarker identification with individual miRNA or mRNA expression data.
Immune-Related Molecular Profiling of Thymoma With Myasthenia Gravis
Authors: Zhuang Jinman , Guan Maohao , Liu Maolin , Liu Yuhang , Yang Shuyan , Hu Zhijian , Lai Fancai , He Fei
Published: October 2021

Background: Approximately 50% of thymoma patients also show myasthenia gravis (MG), which is an autoimmune disease; however, the pathogenesis of MG-associated thymoma remains elusive. Our aim was to investigate immune-related lncRNA profiles of a set of candidate genes for better understanding of the molecular mechanism underlying the pathogenesis of thymoma with or without MG.

Methods: Molecular profiles of thymoma with or without MG were downloaded from The Cancer Genome Atlas, and Pearson’s correlation analysis was performed to identify immune-related lncRNAs. T test was used to examine the differential expression and differential methylation between thymoma patients with or without MG. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to predict the function of target genes of immune-related lncRNAs.

Results: Analyses of the 87 thymoma samples with complete MG information revealed that 205 mRNAs and 56 lncRNAs showed up-regulated expression in thymoma with MG patients, while 458 mRNAs and 84 lncRNAs showed down-regulated expression. The methylation level of three immune-related lncRNAs (AP000787.1, AC004943.1, WT1-AS, FOXG1-AS1) was significantly decreased in thymoma tissues, and the methylation level of these immune-related lncRNAs (WT1-AS: Cor = 0.368, p < 0.001; FOXG1-AS1: Cor = 0.288, p < 0.01; AC004943.1: Cor = -0.236, p < 0.05) correlated with their expression. GO and KEGG pathway analysis revealed that targets of the immune-related lncRNA FOXG1-AS1 were enriched in small GTPase binding and herpes simplex virus 1 infection. Transcription coregulator activity and cell cycle were the most enriched pathways for targets of lncRNA AC004943.1. LncRNA WT1-AS targets were most enriched in actin binding and axon guidance.

Conclusion: Our results revealed the immune-related molecular profiling of thymoma with MG and without MG and identified key pathways involved in the underlying molecular mechanism of thymoma-related MG. These findings provide insights for further research of potential markers for thymoma-related MG.
Immune Regulatory Cell Bias Following Alemtuzumab Treatment in Relapsing-Remitting Multiple Sclerosis
Authors: Kashani Nicole , Kelland Eve E. , Vajdi Borna , Anderson Lauren M. , Gilmore Wendy , Lund Brett T.
Published: October 2021

Alemtuzumab is a highly effective treatment for relapsing-remitting multiple sclerosis. It selectively targets the CD52 antigen to induce profound lymphocyte depletion, followed by recovery of T and B cells with regulatory phenotypes. We previously showed that regulatory T cell function is restored with cellular repletion, but little is known about the functional capacity of regulatory B-cells and peripheral blood monocytes during the repletion phase. In this study (ClinicalTrials.gov ID# NCT03647722) we simultaneously analyzed the change in composition and function of both regulatory lymphocyte populations and distinct monocyte subsets in cross-sectional cohorts of MS patients prior to or 6, 12, 18, 24 or 36 months after their first course of alemtuzumab treatment. We found that the absolute number and percentage of cells with a regulatory B cell phenotype were significantly higher after treatment and were positivity correlated with regulatory T cells. In addition, B cells from treated patients secreted higher levels of IL-10 and BDNF, and inhibited the proliferation of autologous CD4+CD25-T cell targets. Though there was little change in monocytes populations overall, following the second annual course of treatment, CD14+monocytes had a significantly increased anti-inflammatory bias in cytokine secretion patterns. These results confirmed that the immune system in alemtuzumab-treated patients is altered in favor of a regulatory milieu that involves expansion and increased functionality of multiple regulatory populations including B cells, T cells and monocytes. Here, we showed for the first time that functionally competent regulatory B cells re-appear with similar kinetics to that of regulatory T-cells, whereas the change in anti-inflammatory bias of monocytes does not occur until after the second treatment course. These findings justify future studies of all regulatory cell types following alemtuzumab treatment to reveal further insights into mechanisms of drug action, and to identify key immunological predictors of durable clinical efficacy in alemtuzumab-treated patients.
CMV Infection and CMV-Specific Immune Reconstitution Following Haploidentical Stem Cell Transplantation: An Update
Authors: Luo Xiao-Hua , Zhu Yan , Chen Yu-Ting , Shui Li-Ping , Liu Lin
Published: October 2021

Haploidentical stem cell transplantation (haploSCT) has advanced to a common procedure for treating patients with hematological malignancies and immunodeficiency diseases. However, cure is seriously hampered by cytomegalovirus (CMV) infections and delayed immune reconstitution for the majority of haploidentical transplant recipients compared to HLA-matched stem cell transplantation. Three major approaches, includingin vivoT-cell depletion (TCD) using antithymocyte globulin for haploSCT (in vivoTCD-haploSCT),ex vivoTCD using CD34 + positive selection for haploSCT (ex vivoTCD-haploSCT), and T-cell replete haploSCT using posttransplant cyclophosphamide (PTCy-haploSCT), are currently used worldwide. We provide an update on CMV infection and CMV-specific immune recovery in this fast-evolving field. The progress made in cellular immunotherapy of CMV infection after haploSCT is also addressed. Groundwork has been prepared for the creation of personalized avenues to enhance immune reconstitution and decrease the incidence of CMV infection after haploSCT.
Maternal, Decidual, and Neonatal Lymphocyte Composition Is Affected in Pregnant Kidney Transplant Recipients
Authors: Feyaerts Dorien , Gillard Joshua , van Cranenbroek Bram , Rigodanzo Marins Lina , Baghdady Mariam M. S. , Comitini Gaia , Lely A. Titia , van Hamersvelt Henk W. , van der Heijden Olivier W. H. , Joosten Irma , van der Molen Renate G.
Published: October 2021

Pregnancy after renal transplantation is associated with an increased risk of complications. While a delicately balanced uterine immune system is essential for a successful pregnancy, little is known about the uterine immune environment of pregnant kidney transplant recipients. Moreover, children born to kidney transplant recipients are exposed in utero to immunosuppressive drugs, with possible consequences for neonatal outcomes. Here, we defined the effects of kidney transplantation on the immune cell composition during pregnancy with a cohort of kidney transplant recipients as well as healthy controls with uncomplicated pregnancies. Maternal immune cells from peripheral blood were collected during pregnancy as well as from decidua and cord blood obtained after delivery. Multiparameter flow cytometry was used to identify and characterize populations of cells. While systemic immune cell frequencies were altered in kidney transplant patients, immune cell dynamics over the course of pregnancy were largely similar to healthy women. In the decidua of women with a kidney transplant, we observed a decreased frequency of HLA-DR+ Treg, particularly in those treated with tacrolimus versus those that were treated with azathioprine next to tacrolimus, or with azathioprine alone. In addition, both the innate and adaptive neonatal immune system of children born to kidney transplant recipients was significantly altered compared to neonates born from uncomplicated pregnancies. Overall, our findings indicate a significant and distinct impact on the maternal systemic, uterine, and neonatal immune cell composition in pregnant kidney transplant recipients, which could have important consequences for the incidence of pregnancy complications, treatment decisions, and the offspring’s health.
GPR Expression in Intestinal Biopsies From SCT Patients Is Upregulated in GvHD and Is Suppressed by Broad-Spectrum Antibiotics
Authors: Ghimire Sakhila , Weber Daniela , Hippe Katrin , Meedt Elisabeth , Hoepting Matthias , Kattner Anna-Sophia , Hiergeist Andreas , Gessner André , Matos Carina , Ghimire Saroj , Wolff Daniel , Edinger Matthias , Hoffmann Petra , Poeck Hendrik , Herr Wolfgang , Holler Ernst
Published: October 2021

Microbiota can exert immunomodulatory effects by short-chain fatty acids (SCFA) in experimental models of graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-SCT). Therefore we aimed to analyze the expression of SCFAs sensing G-protein coupled receptor GPR109A and GPR43 by quantitative PCR in 338 gastrointestinal (GI) biopsies obtained from 199 adult patients undergoing allo-SCT and assessed the interaction of GPR with FOXP3 expression and regulatory T cell infiltrates. GPR expression was strongly upregulated in patients with stage II-IV GvHD (p=0.000 for GPR109A, p=0.01 for GPR43) and at the onset of GvHD (p 0.000 for GPR109A, p=0.006 for GPR43) and correlated strongly with FOXP3 and NLRP3 expression. The use of broad-spectrum antibiotics (Abx) drastically suppressed GPR expression as well as FOXP3 expression in patients’ gut biopsies (p=0.000 for GPRs, FOXP3 mRNA and FOXP3+ cellular infiltrates). Logistic regression analysis revealed treatment with Abx as an independent factor associated with GPR and FOXP3 loss. The upregulation of GPRs was evident only in the absence of Abx (p=0.001 for GPR109A, p=0.014 for GPR43) at GvHD onset. Thus, GPR expression seems to be upregulated in the presence of commensal bacteria and associates with infiltration of FOXP3+ T regs, suggesting a protective, regenerative immunomodulatory response. However, Abx, which has been shown to induce dysbiosis, interferes with this protective response.
Development of Exhausted Memory Monocytes and Underlying Mechanisms
Authors: Pradhan Kisha , Yi Ziyue , Geng Shuo , Li Liwu
Published: October 2021

Pathogenic inflammation and immuno-suppression are cardinal features of exhausted monocytes increasingly recognized in septic patients and murine models of sepsis. However, underlying mechanisms responsible for the generation of exhausted monocytes have not been addressed. In this report, we examined the generation of exhausted primary murine monocytes through prolonged and repetitive challenges with high dose bacterial endotoxin lipopolysaccharide (LPS). We demonstrated that repetitive LPS challenges skew monocytes into the classically exhausted Ly6Chi population, and deplete the homeostatic non-classical Ly6Clo population, reminiscent of monocyte exhaustion in septic patients. scRNAseq analyses confirmed the expansion of Ly6Chi monocyte cluster, with elevation of pathogenic inflammatory genes previously observed in human septic patients. Furthermore, we identified CD38 as an inflammatory mediator of exhausted monocytes, associated with a drastic depletion of cellular NAD+; elevation of ROS; and compromise of mitochondria respiration, representative of septic monocytes. Mechanistically, we revealed that STAT1 is robustly elevated and sustained in LPS-exhausted monocytes, dependent upon the TRAM adaptor of the TLR4 pathway. TRAM deficient monocytes are largely resistant to LPS-mediated exhaustion, and retain the non-classical homeostatic features. Together, our current study addresses an important yet less-examined area of monocyte exhaustion, by providing phenotypic and mechanistic insights regarding the generation of exhausted monocytes.