bluuebunny/crossref_metadata_2025 huggingface dataset:
Food, Our Common Ground: A Photovoice Study
Authors: Malova Ekaterina , Aerpati Abuduaihaiti , Mao Bingjing , Shah Kinza , Tian Shiyun , Zhang Zhiwei , Harrison Tyler Ronald
Published: March 2021

Research shows that factors like campus food environment, food accessibility, and acculturation may shape students' eating patterns and influence their physical and emotional well-being. Although research has investigated factors that contribute to student food choices, few, if any, prior studies have examined this topic from the perspective of graduate students' own experiences. By utilizing Photovoice methodology, the current study aims to fill the research gap as well as supplement the current literature, providing insights from graduate students' everyday realities and feedback from policymakers. Three overlapping themes emerged across all images: (1) unhealthiness becomes the norm, (2) the convenience of food influences decisions, and (3) healthy food consumption a symbol of cultural identity. The feedback from University policymakers in relation to identified themes revealed two key issues. First, the information about dining options on campus is not visibly present anywhere on campus. Second, much of dining services is designed with undergraduate students in mind. The findings of this study suggested that universities should provide a better environment to promote healthy food consumption, improve students' awareness of healthy options, make healthy options convenient enough to consume, limit students' access to unhealthy food, and consider the needs of international students.
Disruption in Chinese E-Commerce During COVID-19
Authors: Yuan Yuan , Guan Muzhi , Zhou Zhilun , Kim Sundong , Cha Meeyoung , Jin Depeng , Li Yong
Published: March 2021

The recent outbreak of the novel coronavirus (COVID-19) has infected millions of citizens worldwide and claimed many lives. This paper examines the impact of COVID-19 on Chinese e-commerce by analyzing behavioral changes observed on a large online shopping platform. We first conduct a time series analysis to identify product categories that faced the most extensive disruptions. The time-lagged analysis shows that behavioral patterns of shopping actions are highly responsive to the epidemic's development. Based on these findings, we present a consumer demand prediction method by encompassing the epidemic statistics and behavioral features of COVID-19-related products. Experimental results demonstrate that our predictions outperform existing baselines and further extend to long-term and province-level forecasts. Finally, we discuss how our market analysis and prediction can help better prepare for future pandemics by gaining extra time to launch preventive measures.
Effects of Stationary and Transient Transport of Ozone on the Ozone Valley Over the Tibetan Plateau in Summer
Authors: Xu Wenwen , Song Qianqian , Li Yajuan , Shi Chunhua , Sun Bo , Su Yucheng , Tang Zhou , Du Yahan , Guo Dong
Published: March 2021

We studied the effects of the stationary and transient transport of ozone in the upper troposphere and lower stratosphere (UTLS) on the ozone valley over the Tibetan Plateau (OVTP) in summer using the daily ERA-Interim reanalysis dataset for the time period 1979–2016. We used the Lorenz circulation decomposition method to separate the stationary and transient transport of ozone into terms related to either the mean flow or eddies. The decrease in the total ozone concentration in summer is associated with the transport of ozone, which, in turn, reinforces the OVTP. The zonal (meridional) transport of ozone, which combines stationary and transient transport, strengthens (weakens) the ozone valley. The stationary zonal (meridional) transport of ozone strengthens (weakens) the ozone valley. The transient zonal (meridional) transport of ozone weakens (strengthens) the ozone valley, but this effect is weaker than that of stationary transport. The mean flow has the dominant role, especially in the stationary component. The effect of eddies on the zonal transient transport of ozone is as strong as that of the mean flow. For stationary transport, the zonal deviation of ozone transported by the zonal mean flow in the zonal (meridional) direction C(O3∗¯ [u]¯)(C(O3∗¯ [v]¯)) dominates total zonal (meridional) change of ozone C(O3¯ u¯)(C(O3¯ v¯)), which strengthens (weakens) the ozone valley. The transient transport of the zonal mean ozone by eddies (C([O3]′u∗′¯)), the zonal deviation of ozone by the zonal mean flow (C(O3∗′[u]′¯)) and the zonal deviation of ozone by eddies (C(O3∗′u∗′¯)) all have a strong effect on the ozone valley. By contrast, the transient transport of the zonal mean ozone by eddies in the meridional direction (C([O3]′v∗′¯)) has a much weaker and the smallest effect. Both the zonal deviation of ozone by the zonal mean flow and by eddies in the meridional direction (C(O3∗′[v]′¯) and  C(O3∗′v∗′¯)) have major roles in transient meridional transport, but their roles are the opposite of each other. The contributions of stationary and transient transport to zonal transport are consistent, whereas their contributions to meridional transport are the opposite of each other. The influence of transient transport on the formation and maintenance of OVTP is not negligible.
Spatial Distribution of Crusts in Antarctic and Greenland Snowpacks and Implications for Snow and Firn Studies
Authors: Weinhart Alexander H. , Kipfstuhl Sepp , Hörhold Maria , Eisen Olaf , Freitag Johannes
Published: March 2021

The occurrence of snowpack features has been used in the past to classify environmental regimes on the polar ice sheets. Among these features are thin crusts with high density, which contribute to firn stratigraphy and can have significant impact on firn ventilation as well as on remotely inferred properties like accumulation rate or surface mass balance. The importance of crusts in polar snowpack has been acknowledged, but nonetheless little is known about their large-scale distribution. From snow profiles measured by means of microfocus X-ray computer tomography we created a unique dataset showing the spatial distribution of crusts in snow on the East Antarctic Plateau as well as in northern Greenland including a measure for their local variability. With this method, we are able to find also weak and oblique crusts, to count their frequency of occurrence and to measure the high-resolution density. Crusts are local features with a small spatial extent in the range of tens of meters. From several profiles per sampling site we are able to show a decreasing number of crusts in surface snow along a traverse on the East Antarctic Plateau. Combining samples from Antarctica and Greenland with a wide range of annual accumulation rate, we find a positive correlation (R2 = 0.89) between the logarithmic accumulation rate and crusts per annual layer in surface snow. By counting crusts in two Antarctic firn cores, we can show the preservation of crusts with depth and discuss their temporal variability as well as the sensitivity to accumulation rate. In local applications we test the robustness of crusts as a seasonal proxy in comparison to chemical records like impurities or stable water isotopes. While in regions with high accumulation rates the occurrence of crusts shows signs of seasonality, in low accumulation areas dating of the snowpack should be done using a combination of volumetric and stratigraphic elements. Our data can bring new insights for the study of firn permeability, improving of remote sensing signals or the development of new proxies in snow and firn core research.
General Intelligence and Socioeconomic Status as Strong Predictors of Student Performance in Latin American Schools: Evidence From PISA Items
Authors: Flores-Mendoza Carmen , Ardila Ruben , Gallegos Miguel , Reategui-Colareta Norma
Published: March 2021

Numerous technical—scientific reports have demonstrated that student performance variability is linked to several factors, especially socioeconomic factors. For a century, differential psychology has shown that students’ socioeconomic level has little or no relevance in the explanation of student performance variation when the intellectual factor is considered. Here we present a study on a student samples (N= 1264) aged 13 to 16 yrs, enrolled in 32 schools from five Latin American countries (Argentina, Brazil, Chile, Colombia, and Peru). A short version of the PISA test (composed by 16 items) and five cognitive measures were administered, in addition to a socioeconomic questionnaire. Multilevel analysis (marginal models) indicated that general intelligence (g-factor) and socioeconomic school status were robust predictors, and the students’ socioeconomic status very little accounted for the variation in the PISA test. This study concludes that education policy must incorporate individual differences in intelligence, beyond socioeconomic variables, as an important predictor variable in student performance studies.
Eco-Solutioning: The Design and Evaluation of a Curricular Unit to Foster Students’ Creation of Solutions to Address Local Socio-Scientific Issues
Authors: Songer Nancy Butler , Ibarrola Recalde Guillermo D.
Published: March 2021

The global pandemic and climate change have led to unprecedented environmental, social, and economic challenges with interdisciplinary STEM foundations. Even as STEM learning has never been more important, very few pre-college programs prepare students to address these challenges by emphasizing socio-scientific issue (SSI) problem solving and the engineering design of solutions to address local phenomena. The paper discusses the design and evaluation of a pre-college, SSI curricular unit where students expand their learning by creating solutions to increase biodiversity within local urban neighborhoods. The learning approach, which we call eco-solutioning, builds from current vision and policy documents in STEM education emphasizing phenomenon-centric instructional materials, science investigations, and engineering design. The paper outlines design principles for creating an eco-solutioning instructional unit that guides young students to: collect and analyze data on local organisms, use an engineering design approach to craft solutions to increase local biodiversity, and present their solutions to local city planners and community members. Two cycles of research studies evaluated student learning using paired t-tests. Results demonstrated significant pre-post learning outcomes in both research cycles. A third research cycle in the form of a summer extension program supported students as they implemented their local solutions. Conclusions highlight design principles for the successful creation of SSI curricular units centered on local environmental issues of interest to students, teachers, and stakeholders.
Extracorporeal Shock Wave Therapy Promotes Osteogenic Differentiation in a Rabbit Osteoporosis Model
Authors: Li Baofeng , Wang Renkai , Huang Xianyin , Ou Yongliang , Jia Zhenyu , Lin Shanghui , Zhang Ying , Xia Hong , Chen Bei
Published: March 2021

Extracorporeal shock wave therapy (ESWT) has been identified to accelerate bone formation. However, detailed mechanism has not been fully explained. In this study, we found that ESWT promoted osteoblast formation in vitro. Local ESW treatment of femur increased bone formation in vivo. Furthermore, changing the density or frequency of energy, there was no statistical difference in osteogenic differentiation. Therapeutically, local ESW therapy relieved bone loss and increased the number of bone trabecular in a rabbit osteoporosis model and promoted endogenous levels of SMAD2 protein expression. Thus, ESWT may be a potential therapy by promoting osteoblast maturation through TGF-β/SMAD2 pathway.
Counteracting the Negative Effects of Copper Limitations Through the Biostimulatory Action of a Tropical Plant Extract in Grapevine Under Pedo-Climatic Constraints
Authors: Cirillo Chiara , Arena Carmen , Rouphael Youssef , Caputo Rosanna , Amitrano Chiara , Petracca Francesca , De Francesco Sara , Vitale Ermenegilda , Erbaggio Arturo , Bonfante Antonello , De Micco Veronica
Published: March 2021

In southern Mediterranean areas, vineyards are facing the combination of increasing air temperature, drought and frequency of extreme events (e.g., heat waves) due to climate change. Since most of the berry growth and ripening phases occur during the aridity period, such environmental constraints are responsible for limitations in yield and berry quality. Within this scenario, to achieve vineyard sustainability, renewed approaches in vineyard management have been proposed and the use of plant biostimulants seems a prominent and environmental friendly practice. The aim of this study was to test four combinations of a tropical plant extract and conventional chemicals for disease control on morpho-anatomical, physiological, biochemical and berry quality inVitis viniferaL. subsp.vinifera“Aglianico.” In particular, we aimed to evaluate the possibility to counteract the negative effects of the reductions in copper distribution, by applying the tropical plant extract enriched with: micronutrients, enzymes involved in the activation of natural defense, aminoacids, and vitamins. The halved dose of Cu in combination with the tropical plant extract allowed maintaining a reduced vegetative vigor. In the second year of treatment, the addition of the plant extract significantly improved leaf gas exchanges and photochemistry as well as the synthesis of photosynthetic pigments. At berry level, the plant extract induced an increase in phenolics accompanied by a decrease in soluble sugars. The overall results showed that the expected differences in growth performance and productivity in vines are linked to different eco-physiological and structural properties induced by the various treatments. The tropical plant extract also primed plant defenses at the leaf and fruit levels, mainly due to modifications of some structural and biochemical traits, respectively.
Genome-Based Drug Target Identification in Human Pathogen Streptococcus gallolyticus
Authors: Qureshi Nosheen Afzal , Bakhtiar Syeda Marriam , Faheem Muhammad , Shah Mohibullah , Bari Ahmed , Mahmood Hafiz M. , Sohaib Muhammad , Mothana Ramzi A. , Ullah Riaz , Jamal Syed Babar
Published: March 2021

Streptococcus gallolysticus (Sg) is an opportunistic Gram-positive, non-motile bacterium, which causes infective endocarditis, an inflammation of the inner lining of the heart. As Sg has acquired resistance with the available antibiotics, therefore, there is a dire need to find new therapeutic targets and potent drugs to prevent and treat this disease. In the current study, an in silico approach is utilized to link genomic data of Sg species with its proteome to identify putative therapeutic targets. A total of 1,138 core proteins have been identified using pan genomic approach. Further, using subtractive proteomic analysis, a set of 18 proteins, essential for bacteria and non-homologous to host (human), is identified. Out of these 18 proteins, 12 cytoplasmic proteins were selected as potential drug targets. These selected proteins were subjected to molecular docking against drug-like compounds retrieved from ZINC database. Furthermore, the top docked compounds with lower binding energy were identified. In this work, we have identified novel drug and vaccine targets against Sg, of which some have already been reported and validated in other species. Owing to the experimental validation, we believe our methodology and result are significant contribution for drug/vaccine target identification against Sg-caused infective endocarditis.
AI Aided Design of Epitope-Based Vaccine for the Induction of Cellular Immune Responses Against SARS-CoV-2
Authors: Mazzocco Giovanni , Niemiec Iga , Myronov Alexander , Skoczylas Piotr , Kaczmarczyk Jan , Sanecka-Duin Anna , Gruba Katarzyna , Król Paulina , Drwal Michał , Szczepanik Marian , Pyrc Krzysztof , Stȩpniak Piotr
Published: March 2021

The heavy burden imposed by the COVID-19 pandemic on our society triggered the race toward the development of therapies or preventive strategies. Among these, antibodies and vaccines are particularly attractive because of their high specificity, low probability of drug-drug interaction, and potentially long-standing protective effects. While the threat at hand justifies the pace of research, the implementation of therapeutic strategies cannot be exempted from safety considerations. There are several potential adverse events reported after the vaccination or antibody therapy, but two are of utmost importance: antibody-dependent enhancement (ADE) and cytokine storm syndrome (CSS). On the other hand, the depletion or exhaustion of T-cells has been reported to be associated with worse prognosis in COVID-19 patients. This observation suggests a potential role of vaccines eliciting cellular immunity, which might simultaneously limit the risk of ADE and CSS. Such risk was proposed to be associated with FcR-induced activation of proinflammatory macrophages (M1) by Fu et al. (2020) and Iwasaki and Yang (2020). All aspects of the newly developed vaccine (including the route of administration, delivery system, and adjuvant selection) may affect its effectiveness and safety. In this work we use a novel in silico approach (based on AI and bioinformatics methods) developed to support the design of epitope-based vaccines. We evaluated the capabilities of our method for predicting the immunogenicity of epitopes. Next, the results of our approach were compared with other vaccine-design strategies reported in the literature. The risk of immuno-toxicity was also assessed. The analysis of epitope conservation among other Coronaviridae was carried out in order to facilitate the selection of peptides shared across different SARS-CoV-2 strains and which might be conserved in emerging zootic coronavirus strains. Finally, the potential applicability of the selected epitopes for the development of a vaccine eliciting cellular immunity for COVID-19 was discussed, highlighting the benefits and challenges of such an approach.
Genetic Variants in TNFSF4 and TNFSF8 Are Associated With the Risk of HCV Infection Among Chinese High-Risk Population
Authors: Fu Zuqiang , Cai Weihua , Shao Jianguo , Xue Hong , Ge Zhijun , Fan Haozhi , Dong Chen , Wang Chunhui , Zhang Jinwei , Shen Chao , Zhang Yun , Huang Peng , Yue Ming
Published: March 2021

Background

The tumor necrosis factor superfamily (TNFSF) and TNF receptor superfamily (TNFRSF) play important roles in the immune responses to infections. The aim of this study was to determine the impact of single nucleotide polymorphisms (SNPs) of several TNFSF/TNFRSF genes on the risk of hepatitis C virus (HCV) infection in the Chinese high-risk population.

Methods

The TNFSF4-rs1234313, TNFSF4-rs7514229, TNFSF8-rs3181366, TNFSF8-rs2295800, TNFRSF8-rs2298209, and TNFRSF8-rs2230625 SNPs were genotyped in 2309 uninfected controls, 597 subjects with spontaneous HCV clearance and 784 patients with persistent HCV infection using the TaqMan-MGB assay. The putative functions of the positive SNPs were determined using online bioinformatics tools.

Results

After adjusting for gender, age, high-risk population, alanine transaminase (ALT), aspartate aminotransferase (AST), IL28B-rs12979860 and rs8099917 genotypes, the non-conditional logistic regression showed that rs7514229-T, rs3181366-T, and rs2295800-C were associated with an increased risk of HCV infection (all PFDR < 0.05). Combined analysis of rs7514229-T and rs3181366-T risk alleles showed that the subjects carrying 2–4 risk alleles were more susceptible to HCV infection compared with those lacking any risk allele (all P < 0.001). Furthermore, the risk of HCV infection increased with the number of risk alleles (Ptrend < 0.001). In silico analysis showed that rs7514229, rs3181366, and rs2295800 polymorphisms may affect the transcription of mRNA by regulating miRNA binding, TF binding, and promoter activation, respectively, which may have biological consequences.

Conclusion

TNFSF4-rs7514229, TNFSF8-rs3181366, and TNFSF8-rs2295800 are associated with increased risk of HCV infection in the Chinese high-risk population.
Autoreactive Peripheral Blood T Helper Cell Responses in Bullous Pemphigoid and Elderly Patients With Pruritic Disorders
Authors: Didona Dario , Scarsella Luca , Fehresti Milad , Solimani Farzan , Juratli Hazem A. , Göbel Manuel , Mühlenbein Stefan , Holiangu Lily , Pieper Josquin , Korff Vera , Schmidt Thomas , Sitaru Cassian , Eming Rüdiger , Hertl Michael , Pollmann Robert
Published: March 2021

Bullous pemphigoid (BP) is a prototypic autoimmune disorder of the elderly, characterized by serum IgG autoantibodies, namely anti-BP180 and anti-BP230, directed against components of the basal membrane zone that lead to sub-epidermal loss of adhesion. Pruritus may be indicative of a pre-clinical stage of BP, since a subset of these patients shows serum IgG autoantibodies against BP230 and/or BP180 while chronic pruritus is increasingly common in the elderly population and is associated with a variety of dermatoses. Clinical and experimental evidence further suggests that pruritus of the elderly may be linked to autoimmunity with loss of self-tolerance against cutaneous autoantigens. Thus, the objective of this study was to determine autoreactive T cell responses against BP180 in elderly patients in comparison to patients with BP. A total of 22 elderly patients with pruritic disorders, 34 patients with bullous or non-bullous BP and 34 age-matched healthy controls were included in this study. The level of anti-BP180 and anti-BP230 IgG serum autoantibodies, Bullous Pemphigoid Disease Area Index (BPDAI), and pruritus severity were assessed for all patients and controls. For characterization of the autoreactive T cell response, peripheral blood mononuclear cells were stimulated ex vivo with recombinant BP180 proteins (NH2- and COOH-terminal domains) and the frequencies of BP180-specific T cells producing interferon-γ, interleukin (IL)-5 or IL-17 were subsequently determined by ELISpot assay. Patients with BP showed a mixed Th1/Th2 response against BP180 while autoreactive Th1 cells were identified in a minor subset of elderly patients with pruritic disorders. Furthermore, our T cell characterization revealed that therapeutic application of topical clobetasol propionate ointment in BP patients significantly reduced peripheral blood BP180-specific T cells, along with clinically improved symptoms, strongly suggesting a systemic immunosuppressive effect of this treatment.
C-Reactive Protein Suppresses the Th17 Response Indirectly by Attenuating the Antigen Presentation Ability of Monocyte Derived Dendritic Cells in Experimental Autoimmune Encephalomyelitis
Authors: Shen Zhi-Yuan , Zheng Yi , Pecsok Maggie K. , Wang Ke , Li Wei , Gong Min-Jie , Wu Feng , Zhang Lin
Published: March 2021

Experimental autoimmune encephalomyelitis (EAE) is a classical murine model for Multiple Sclerosis (MS), a human autoimmune disease characterized by Th1 and Th17 responses. Numerous studies have reported that C-reactive protein (CRP) mitigates EAE severity, but studies on the relevant pathologic mechanisms are insufficient. Our previous study found that CRP suppresses Th1 response directly by receptor binding on naïve T cells; however, we did not observe the effect on Th17 response at that time; thus it remains unclear whether CRP could regulate Th17 response. In this study, we verified the downregulation of Th17 response by a single-dose CRP injection in MOG-immunized EAE mice in vivo while the direct and indirect effects of CRP on Th17 response were differentiated by comparing its actions on isolated CD4+ T cells and splenocytes in vitro, respectively. Moreover, the immune cell composition was examined in the blood and CNS (Central Nervous System), and a blood (monocytes) to CNS (dendritic cells) infiltration pathway is established in the course of EAE development. The infiltrated monocyte derived DCs (moDCs) were proved to be the only candidate antigen presenting cells to execute CRP’s function. Conversely, the decrease of Th17 responses caused by CRP disappeared in the above in vivo and in vitro studies with FcγR2B−/− mice, indicating that FcγR2B expressed on moDCs mediates CRP function. Furthermore, peripheral blood monocytes were isolated and induced to establish moDCs, which were used to demonstrate that the antigen presenting ability of moDCs was attenuated by CRP through FcγR2B, and then NF-κB and ERK signaling pathways were manifested to be involved in this regulation. Ultimately, we perfected and enriched the mechanism studies of CRP in EAE remission, so we are more convinced that CRP plays a key role in protecting against EAE development, which may be a potential therapeutic target for the treatment of MS in human.
Thermoneutrality Alters Gastrointestinal Antigen Passage Patterning and Predisposes to Oral Antigen Sensitization in Mice
Authors: Noah Taeko K. , Lee Jee-Boong , Brown Christopher A. , Yamani Amnah , Tomar Sunil , Ganesan Varsha , Newberry Rodney D. , Huffnagle Gary B. , Divanovic Senad , Hogan Simon P.
Published: March 2021

Food allergy is an emerging epidemic, and the underlying mechanisms are not well defined partly due to the lack of robust adjuvant free experimental models of dietary antigen sensitization. As housing mice at thermoneutrality (Tn) - the temperature of metabolic homeostasis (26–30°C) – has been shown to improve modeling various human diseases involved in inflammation, we tested the impact of Tn housing on an experimental model of food sensitization. Here we demonstrate that WT BALB/c mice housed under standard temperature (18–20°C, Ts) conditions translocated the luminal antigens in the small intestine (SI) across the epithelium via goblet cell antigen passages (GAPs). In contrast, food allergy sensitive Il4raF709 mice housed under standard temperature conditions translocated the luminal antigens in the SI across the epithelium via secretory antigen passages (SAPs). Activation of SI antigen passages and oral challenge of Il4raF709 mice with egg allergens at standard temperature predisposed Il4raF709 mice to develop an anaphylactic reaction. Housing Il4raF709 mice at Tn altered systemic type 2 cytokine, IL-4, and the landscape of SI antigen passage patterning (villus and crypt involvement). Activation of SI antigen passages and oral challenge of Il4raF709 mice with egg antigen under Tn conditions led to the robust induction of egg-specific IgE and development of food-induced mast cell activation and hypovolemic shock. Similarly, Tn housing of WT BALB/c mice altered the cellular patterning of SI antigen passage (GAPs to SAPs). Activation of SI antigen passages and the oral challenge of WT BALB/c mice with egg antigen led to systemic reactivity to egg and mast cell activation. Together these data demonstrate that Tn housing alters antigen passage cellular patterning and landscape, and concurrent oral exposure of egg antigens and SAP activation is sufficient to induce oral antigen sensitization.
Variants at the MHC Region Associate With Susceptibility to Clostridioides difficile Infection: A Genome-Wide Association Study Using Comprehensive Electronic Health Records
Authors: Li Jiang , Zhang Yanfei , Jilg Alexandria L. , Wolk Donna M. , Khara Harshit S. , Kolinovsky Amy , Rolston David D. K. , Hontecillas Raquel , Bassaganya-Riera Josep , Williams Marc S. , Abedi Vida , Lee Ming Ta Michael
Published: March 2021

Background

Clostridioides difficile is a major cause of healthcare-associated and community-acquired diarrhea. Host genetic susceptibility to Clostridioides difficile infection has not been studied on a large-scale.

Methods

A total of 1,160 Clostridioides difficile infection cases and 15,304 controls were identified by applying the eMERGE Clostridioides difficile infection algorithm to electronic health record data. A genome-wide association study was performed using a linear mixed model, adjusted for significant covariates in the full dataset and the antibiotic subgroup. Colocalization and MetaXcan were performed to identify potential target genes in Clostridioides difficile infection - relevant tissue types.

Results

No significant genome-wide association was found in the meta-analyses of the full Clostridioides difficile infection dataset. One genome-wide significant variant, rs114751021, was identified (OR = 2.42; 95%CI = 1.84-3.11; p=4.50 x 10-8) at the major histocompatibility complex region associated with Clostridioides difficile infection in the antibiotic group. Colocalization and MetaXcan identified MICA, C4A/C4B, and NOTCH4 as potential target genes. Down-regulation of MICA, upregulation of C4A and NOTCH4 was associated with a higher risk for Clostridioides difficile infection.

Conclusions

Leveraging the EHR and genetic data, genome-wide association, and fine-mapping techniques, this study identified variants and genes associated with Clostridioides difficile infection, provided insights into host immune mechanisms, and described the potential for novel treatment strategies for Clostridioides difficile infection. Future replication and functional validation are needed.
Tolerance to Proinsulin-1 Reduces Autoimmune Diabetes in NOD Mice
Authors: Jhala Gaurang , Selck Claudia , Chee Jonathan , Kwong Chun-Ting J. , Pappas Evan G. , Thomas Helen E. , Kay Thomas W.H. , Krishnamurthy Balasubramanian
Published: March 2021

T-cell responses to insulin and its precursor proinsulin are central to islet autoimmunity in humans and non-obese diabetic (NOD) mice that spontaneously develop autoimmune diabetes. Mice have two proinsulin genes proinsulin -1 and 2 that are differentially expressed, with predominant proinsulin-2 expression in the thymus and proinsulin-1 in islet beta-cells. In contrast to proinsulin-2, proinsulin-1 knockout NOD mice are protected from autoimmune diabetes. This indicates that proinsulin-1 epitopes in beta-cells maybe preferentially targeted by autoreactive T cells. To study the contribution of proinsulin-1 reactive T cells in autoimmune diabetes, we generated transgenic NOD mice with tetracycline-regulated expression of proinsulin-1 in antigen presenting cells (TIP-1 mice) with an aim to induce immune tolerance. TIP-1 mice displayed a significantly reduced incidence of spontaneous diabetes, which was associated with reduced severity of insulitis and insulin autoantibody development. Antigen experienced proinsulin specific T cells were significantly reduced in in TIP-1 mice indicating immune tolerance. Moreover, T cells from TIP-1 mice expressing proinsulin-1 transferred diabetes at a significantly reduced frequency. However, proinsulin-1 expression in APCs had minimal impact on the immune responses to the downstream antigen islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) and did not prevent diabetes in NOD 8.3 mice with a pre-existing repertoire of IGRP reactive T cells. Thus, boosting immune tolerance to proinsulin-1 partially prevents islet-autoimmunity. This study further extends the previously established role of proinsulin-1 epitopes in autoimmune diabetes in NOD mice.
Kinetics of the Cellular and Transcriptomic Response to Eimeria maxima in Relatively Resistant and Susceptible Chicken Lines
Authors: Bremner Abi , Kim Sungwon , Morris Katrina M. , Nolan Matthew John , Borowska Dominika , Wu Zhiguang , Tomley Fiona , Blake Damer P. , Hawken Rachel , Kaiser Pete , Vervelde Lonneke
Published: March 2021

Eimeria maximais a common cause of coccidiosis in chickens, a disease that has a huge economic impact on poultry production. Knowledge of immunity toE. maximaand the specific mechanisms that contribute to differing levels of resistance observed between chicken breeds and between congenic lines derived from a single breed of chickens is required. This study aimed to define differences in the kinetics of the immune response of two inbred lines of White Leghorn chickens that exhibit differential resistance (line C.B12) or susceptibility (line 15I) to infection byE. maxima. Line C.B12 and 15I chickens were infected withE. maximaand transcriptome analysis of jejunal tissue was performed at 2, 4, 6 and 8 days post-infection (dpi). RNA-Seq analysis revealed differences in the rapidity and magnitude of cytokine transcription responses post-infection between the two lines. In particular, IFN-γ and IL-10 transcript expression increased in the jejunum earlier in line C.B12 (at 4 dpi) compared to line 15I (at 6 dpi). Line C.B12 chickens exhibited increases ofIFNGandIL10mRNA in the jejunum at 4 dpi, whereas in line 15I transcription was delayed but increased to a greater extent. RT-qPCR and ELISAs confirmed the results of the transcriptomic study. Higher serum IL-10 correlated strongly with higherE. maximareplication in line 15I compared to line C.B12 chickens. Overall, the findings suggest early induction of the IFN-γ and IL-10 responses, as well as immune-related genes includingIL21at 4 dpi identified by RNA-Seq, may be key to resistance toE. maxima.
Multi-Dimensional Gene Regulation in Innate and Adaptive Lymphocytes: A View From Regulomes
Authors: Fernando Nilisha , Sciumè Giuseppe , O’Shea John J. , Shih Han-Yu
Published: March 2021

The precise control of cytokine production by innate lymphoid cells (ILCs) and their T cell adaptive system counterparts is critical to mounting a proper host defense immune response without inducing collateral damage and autoimmunity. Unlike T cells that differentiate into functionally divergent subsets upon antigen recognition, ILCs are developmentally programmed to rapidly respond to environmental signals in a polarized manner, without the need of T cell receptor (TCR) signaling. The specification of cytokine production relies on dynamic regulation of cis-regulatory elements that involve multi-dimensional epigenetic mechanisms, including DNA methylation, transcription factor binding, histone modification and DNA-DNA interactions that form chromatin loops. How these different layers of gene regulation coordinate with each other to fine tune cytokine production, and whether ILCs and their T cell analogs utilize the same regulatory strategy, remain largely unknown. Herein, we review the molecular mechanisms that underlie cell identity and functionality of helper T cells and ILCs, focusing on networks of transcription factors and cis-regulatory elements. We discuss how higher-order chromatin architecture orchestrates these components to construct lineage- and state-specific regulomes that support ordered immunoregulation.
Delays in Protecting a Small Endangered Cetacean: Lessons Learned for Science and Management
Authors: Slooten Elisabeth , Dawson Stephen M.
Published: March 2021

Hector’s dolphin is a small, endangered dolphin species found exclusively in the inshore coastal waters of New Zealand. We draw on 36 years of involvement in research on Hector’s dolphin, and its subspecies Māui dolphin, to provide an overview of the species’ conservation biology, and summarize the incremental progress towards sustainable management. We offer lessons learned at the interface between science and management. These lessons emphasize the importance of acting early, having clear management goals and ensuring that the area over which protection measures are applied is sufficiently large to be biologically relevant. High-quality information is vital, but gaining appropriate conservation outcomes depends also on social and political processes. We warn that compromise can have high biological costs and that representation on stakeholder groups is usually biased toward extractive users and short-term economic perspectives. In New Zealand, outcomes have depended closely on politics; the greatest gains have been made when relevant government ministers took a special interest. Scientists have crucial roles in every phase of this process. Each country and each species will present their own challenges and opportunities. We trust, however, that lessons learned from Hector’s dolphin conservation will be useful to researchers and managers elsewhere.
Morphological and Genetic Recovery of Coral Polyps After Bail-Out
Authors: Chuang Po-Shun , Ishikawa Kota , Mitarai Satoshi
Published: March 2021

Contemporary advances in microfluidic and molecular techniques have enabled coral studies to shift from reef and colony scales to polyp- and molecular-level investigations. Polyp bail-out provides an alternative approach to acquire solitary polyps for studies at finer scales. Although induction of polyp bail-out has been reported in several studies, polyp health after bail-out has not been investigated. In this study, we monitored morphological and genetic changes inPocillopora acutapolyps after bail-out induced by hyperosmosis. In isosmotic conditions, over 80% of bailed-out polyps survived, of which half regenerated normal polyp morphology within 5 days, including a polarized polyp body, extended tentacles, and a distinguishable oral disk. In contrast, the remaining polyps degenerated into tissue ball-like structures that resemble multicellular aggregates reported in earlier studies. In morphologically recovered polyps, transcriptomic analysis showed that ∼87% of genes altered during bail-out induction recovered from stress status, suggesting resumption of metabolism, cell division, and immunity, while in degenerated polyps, only ∼71% of genes recovered. Quantitative polymerase chain reaction data further demonstrated that genetic recovery of energy production, cell proliferation, and immune response was achieved in morphologically recovered polyps within 3 days after bail-out, but was not fully accomplished in degenerated polyps even after 5 days. Our findings indicate that solitary polyps generated by hyperosmosis-induced bail-out can recover rapidly from physiological stress under laboratory conditions, suggesting that bailed-out polyps could be used as new models for coral research.
Understanding Effects of Whale-Watching Vessel Noise on Humpback Whale Song in the North Pacific Coast of Colombia With Propagation Models of Masking and Acoustic Data Observations
Authors: Rey-Baquero Maria Paula , Huertas-Amaya Laura Valentina , Seger Kerri D. , Botero-Acosta Natalia , Luna-Acosta Andrea , Perazio Christina E. , Boyle John K. , Rosenthal Sarah , Vallejo Ann Carole
Published: March 2021

Soundscapes with minimal anthropogenic noise sources are key for the survival and effective communication of marine mammals. The Gulf of Tribugá is part of the breeding ground for humpback whale Stock G. Currently, no large-scale infrastructure exists on the Gulf's coastline, making it an area with high biodiversity and little anthropogenic noise. Whale-watching is one of the few human activities that contributes to the soundscape. By Morro Mico, on the southern limit of the Utría Natural National Park, an Ecological Acoustic Recorder (EAR, Oceanwide Science Institute) was deployed in the Gulf to record samples of acoustic activity from October to November 2018. It recorded for 10-min intervals with 20-min lapses for a duty cycle of 33.3%. One of the common peak frequencies of humpback whale song units from these recordings was used as input to an acoustic propagation model using the parabolic equation to simulate the communication space of a humpback whale when zero, one, and two boats are present. GPS positions of theodolite data from various whale watching scenarios in the Gulf were used to inform the models. Model results indicate that humpback whale song communication space could be reduced by as much as 63% in the presence of even one whale-watching boat. The boats traveling through the Gulf are the same as those used in whale-watching, and their engine noise while passing Morro Mico coincided with song structural and temporal changes observed in the acoustic data. Combiningin situdata with acoustic models can advance the understanding of the spatio-temporal acoustic reactions of whales when their vocalizations are masked by boat noise. This project serves as an approximation of how humpback whale Stock G may respond to whale-watching vessel noise in the Gulf of Tribugá.
Formalin-Fixed Fish Larvae Could Be Effectively Identified by DNA Barcodes: A Case Study on Thousands of Specimens in South China Sea
Authors: Hou Gang , Chen Yanying , Wang Sijin , Wang Jinrun , Chen Weitao , Zhang Hui
Published: March 2021

Delimiting ichthyoplankton is fundamental work for monitoring the recruitment process and identifying the spawning and nursing grounds of fishes. Nevertheless, it is extremely difficult to identify the fish during the early stages at the species level based on morphological characters because of the paucity of diagnostic features. In this study, we investigated the fish larval community through large-scale ecosystemic sampling in South China Sea (SCS) during 2013 and 2017 using DNA barcodes. To maintain the morphologies of fish larvae, we preserved the larvae in formalin and developed a technique to recover their DNA. Among the 3,500 chosen larvae, we successfully extracted DNA from 2,787 larval samples and obtained 1,006 high-quality sequences. Blast searches showed that 408 larvae (i.e., 40.5%) could be unambiguously identified to species, 413 larvae (i.e., 41.1%) were ambiguously species delimitation, and 185 larvae (i.e., 18.4%) showed a low match similarity with target sequences. A total of 101 species were identified, among which 38 and 33 species corresponded to demersal and reef-associated species, whereas the remaining 30 species corresponded to benthopelagic, pelagic-oceanic, bathypelagic, and pelagic-neritic species. High-quality larval photographs of the 101 diagnosed species showed intact morphological characters and thus provided a reference for identifying fish species during the early stages based on morphological characters. Our study highlighted the possibility of recovering and amplifying DNA from formalin-fixed samples and provided new insight into the fish larval community in the SCS.
Workflow for the Generation of Expert-Derived Training and Validation Data: A View to Global Scale Habitat Mapping
Authors: Roelfsema Chris M. , Lyons Mitchell , Murray Nicholas , Kovacs Eva M. , Kennedy Emma , Markey Kathryn , Borrego-Acevedo Rodney , Ordoñez Alvarez Alexandra , Say Chantel , Tudman Paul , Roe Meredith , Wolff Jeremy , Traganos Dimosthenis , Asner Gregory P. , Bambic Brianna , Free Brian , Fox Helen E. , Lieb Zoe , Phinn Stuart R.
Published: March 2021

Our ability to completely and repeatedly map natural environments at a global scale have increased significantly over the past decade. These advances are from delivery of a range of on-line global satellite image archives and global-scale processing capabilities, along with improved spatial and temporal resolution satellite imagery. The ability to accurately train and validate these global scale-mapping programs from what we will call “reference data sets” is challenging due to a lack of coordinated financial and personnel resourcing, and standardized methods to collate reference datasets at global spatial extents. Here, we present an expert-driven approach for generating training and validation data on a global scale, with the view to mapping the world’s coral reefs. Global reefs were first stratified into approximate biogeographic regions, then per region reference data sets were compiled that include existing point data or maps at various levels of accuracy. These reference data sets were compiled from new field surveys, literature review of published surveys, and from individually sourced contributions from the coral reef monitoring and management agencies. Reference data were overlaid on high spatial resolution satellite image mosaics (3.7 m × 3.7 m pixels; Planet Dove) for each region. Additionally, thirty to forty satellite image tiles; 20 km × 20 km) were selected for which reference data and/or expert knowledge was available and which covered a representative range of habitats. The satellite image tiles were segmented into interpretable groups of pixels which were manually labeled with a mapping category via expert interpretation. The labeled segments were used to generate points to train the mapping models, and to validate or assess accuracy. The workflow for desktop reference data creation that we present expands and up-scales traditional approaches of expert-driven interpretation for both manual habitat mapping and map training/validation. We apply the reference data creation methods in the context of global coral reef mapping, though our approach is broadly applicable to any environment. Transparent processes for training and validation are critical for usability as big data provide more opportunities for managers and scientists to use global mapping products for science and conservation of vulnerable and rapidly changing ecosystems.
Accuracy and Prognosis Value of the Sequential Organ Failure Assessment Score Combined With C-Reactive Protein in Patients With Complicated Infective Endocarditis
Authors: Lin Yaowang , Dong Shaohong , Yuan Jie , Yu Danqing , Bei Weijie , Chen Ruimian , Qin Haiyan
Published: March 2021

This study aimed to evaluate the accuracy and prognostic value of the sequential organ failure assessment (SOFA) score combined with C-reactive protein (CRP) in patients with complicated infective endocarditis (IE). A total of 246 consecutive patients with complicated IE were included in the multicentric prospective observational study. These patients were divided into four groups depending on the SOFA score and CRP optimal cutoff values (≥5 points and ≥17.6 mg/L, respectively), which were determined using the receiver operating characteristic analysis: low SOFA and low CRP (n = 83), low SOFA and high CRP (n = 87), high SOFA and low CRP (n = 25), and high SOFA and high CRP (n = 51). The primary endpoint was in-hospital death, and the secondary endpoint was long-time mortality, defined as subsequent readmission and 3-years mortality in the follow-up period. High SOFA score and high CRP were associated with approximately 29.410% (15/51) of higher incidence of in-hospital death with an area under the curve of 0.872. Multivariate analyses showed that age [odds ratio (OR) = 2.242, 1.142–4.401], neurological failure (Glasgow Coma Scale ≤ 12) (OR = 2.513, 1.041–4.224), Staphylococcus aureus (OR = 2.151, 1.252–4.513), SOFA ≥ 5 (OR = 9.320, 3.621–16.847), and surgical treatment (OR = 0.121, 0.031–0.342) were clinical predictors for in-hospital death. On following up for 12–36 months, SOFA ≥ 5 (p = 0.000) showed higher mortality. A high SOFA score combined with increased CRP levels is associated with in-hospital mortality. Also, SOFA score, but not CRP, predicts long-term mortality in complicated IE.