bluuebunny/crossref_metadata_2025 huggingface dataset:
3D Virtual modelling, 3D printing and extended reality for planning of implant procedure of short-term and long-term mechanical circulatory support devices and heart transplantation
Authors: Stepanenko Alexander , Perez Laura Maroto , Ferre Jordi Candela , Ybarra Falcón Cristina , Pérez de la Sota Enrique , San Roman Jose Alberto , Redondo Diéguez Alfredo , Baladron Carlos
Published: July 2023

Introduction

The use of three-dimensional (3D) reconstruction and printing technology, together with extended reality applied to advanced heart failure adult patients with complex anatomy, is rapidly spreading in clinical practice. We report practical experience with application to acute and chronic heart failure: planning and performing mechanical circulatory device insertion or heart transplantation.

Methods

From November 2019 until February 2022, 53 3D virtual biomodels were produced for intervention planning (using Virtual/Augmented Reality and/or 3D printing), following a specific segmentation and preprocessing workflow for biomodelling, in patients with advanced heart failure due to structural heart disease or cardiomyopathies. Four of those patients were complex cases requiring mechanical circulatory support implant procedures in our center.

Results

One short-term and three long-term ventricular assist device system were successfully clinically implanted after application of this technique. In other two cases with extremely high procedural risk, visualized after application of this multimodality imaging, heart transplantation was elected.

Conclusion

3D printing based planning and virtual procedure simulation, are of great importance to select appropriate candidates for mechanical circulatory support in case of complex patient anatomy and may help to diminish periprocedural complications. Extended reality represents a perspective tool in planification of complex surgical procedures or ventricular assist device insertion in this setting.
Integrative single-cell analysis of cardiac and pulmonary sarcoidosis using publicly available cardiac and bronchoalveolar lavage fluid sequencing datasets
Authors: Daoud Abdel , Lema Diego A. , Won Taejoon , Čiháková Daniela
Published: July 2023

Introduction

Cardiac presentation of autoimmune sarcoidosis, known as cardiac sarcoidosis (CS), is a poorly understood disease with high mortality and low diagnosis rate. While CS is an immunological syndrome, little is known about how cardiac parenchymal and stromal cells mediate its pathogenesis. Moreover, while most current sarcoidosis research is based on research in pulmonary sarcoidosis (PS), it remains unclear how much both presentations of sarcoidosis overlap. To tackle these concerns, we leveraged publicly available sarcoidosis transcriptomic datasets.

Methods

Two publicly available bronchoalveolar lavage single-cell RNA sequencing datasets were integrated to analyze PS relative to control. Additionally, two publicly available cardiac single-nucleus RNA sequencing datasets were integrated to analyze CS relative to control. Following integration, we ran cell-cell communication, transcription factor, and differential expression analyses on parenchymal, stromal, and immune subsets identified in our analysis.

Results

Our analysis revealed that there was an expansion of stromal and immune cells in PS and CS. We also observed upregulation of Th17.1 and attenuated activation transcriptional profiles in the immune cells of CS and PS relative to control. Additionally, we found upregulation of pro-inflammatory and pro-fibrotic transcriptional profiles in the cardiac stromal cells of CS relative to control. We also found that cardiomyocytes exhibited upregulated cardiac stress and proliferation transcriptional profiles in CS relative to control.

Conclusions

Our integrative transcriptomic analysis shows that despite tissue-specific differences, there are shared transcriptional trends between CS and PS. It also shows that stromal and parenchymal populations exhibit transcriptional trends that could explain their pathogenic role in CS.
Children's social network size is related to their perspective-taking skills
Authors: Burke Nicole , Brezack Natalie , Meyer Marlene , Woodward Amanda
Published: July 2023

Perspective-taking (PT) is an important skill children develop within the first few years of life; however, little is known about how children's social environments relate to PT development. During early childhood, children's social networks undergo dramatic growth. Prior work with adults has shown that network size is related to PT skill, which raises the question of whether and how children's social networks may relate to their emerging PT skills. This question is particularly interesting given that children's social worlds undergo dramatic growth and changes, which is a sharp contrast from adults that have stable social network sizes. The present study measured the social networks of 3-year-old children (n = 36; 15 female; 68% White) and found that children in larger social networks demonstrated stronger PT skills, particularly on the more difficult trials on the task. These results indicate the size of children's social networks relates to their PT ability.
Interannual and decadal variabilities of phytoplankton community in the Bering Sea and the Arctic Ocean: a case study of relationship with ENSO and Arctic Oscillation abnormity
Authors: Liu Qian , Yang Dan , Zhang Haisheng , Lu Bing
Published: July 2023

We used molecular biomarkers (brassicasterol, dinosterol and C37 alkenones) measured from the surface sediments of the Bering Sea, the Chukchi Sea and the western Arctic Ocean in years of 1999 and 2010 to represent the groups of phytoplankton (diatoms, dinoflagellates and coccolithophores) and reconstruct the phytoplankton composition structure and biomass. The distribution of concentrations of three biomarkers were compatible to previous studies on measured phytoplankton, which showed that the phytoplankton biomass was most abundant in the Chukchi Sea, followed by the Bering Sea and the western Arctic Ocean, and diatoms were the dominant group. It suggests that molecular biomarkers are the suitable indicators of phytoplankton composition, structure and abundance. A record of biomarkers in a sediment core (NB01) collected at the Bering Sea in 2010 presented that the biomass of three phytoplankton groups increased in past 107 years, and their variation patterns were consistent. The synchronous increase of concentrations of phytoplankton biomarkers and cholesterol, a proxy of zooplankton biomass, implied that the primary production increased intensely in the last hundreds of years, corresponding to the trend of sea-ice melting as a result of global warming. Moreover, our results suggested that the combined effect of the anormal interannual changes of the El Niño-Southern Oscillation (ENSO) and the Arctic Oscillations (AO) played a key role in regulating the interannual and decadal variations of phytoplankton biomass and community composition, giving us an insight into the impact of atmospheric circulation on phytoplankton production and carbon flux in the Arctic seas.
Embracing the inclusion of societal concepts in biology improves student understanding
Authors: Adams Paula E. , Driessen Emily P. , Granados Enya , Ragland Penny , Henning Jeremiah A. , Beatty Abby E. , Ballen Cissy J.
Published: July 2023

Understanding the relationship between science and society is included as a core competency for biology students in the United States. However, traditional undergraduate biology instruction emphasizes scientific practice and generally avoids potentially controversial issues at the intersection of science and society, such as representation in STEM, historical unethical research experiments, biology of sex and gender, and environmental justice. As calls grow to highlight this core competency, it is critical we investigate the impact of including these topics in undergraduate biology education. Here, we implemented a semester-long ideological awareness curriculum that emphasized biases, stereotypes, and assumptions that have shaped historical and contemporary science. We taught this curriculum to one section of a non-majors introductory biology course and compared the outcomes to a section of the same course taught using traditional biology content (hereafter the ‘traditional’ section) that did not emphasize societal topics. Both sections of students created concept maps for their final exam, which we coded for ‘society’ and ‘biology’ content. We then assessed (1) the amount of societal content included in the concept maps, and (2) which societal topics were mentioned in each section. We found that students in the ideologically aware section included more societal content in their concept maps than the students in the traditional section. Students exposed to the ideological awareness modules often mentioned the topics covered in those modules, whereas students in the traditional section most commonly mentioned faulty scientific information such as pseudoscience or non-credible research, which was emphasized in the first chapter of the required text-book for both sections. Our results show students who were not engaged in activities about ideological awareness in biology had fewer notions of how society impacts science at the end of the semester. These findings highlight the importance of intentionally teaching students the bidirectional impacts of science and society.
Evaluating student evaluations: evidence of gender bias against women in higher education based on perceived learning and instructor personality
Authors: Khokhlova Olga , Lamba Nishtha , Kishore Sameer
Published: July 2023

Given student evaluations are an integral part of academic employment and progression in higher education, it is crucial to explore various biases amongst students that may influence their ratings. Several studies report a clear gender bias in student evaluation where male instructors receive significantly higher ratings as compared to female instructors. However, there is very limited research about gender biases in underrepresented samples such as South Asia and the Middle East. We examined whether perception of male and female instructors differed in terms of how they facilitate learning and level of engagement, using an experimental design. Six hundred and seventy-one university students were asked to watch a video of an online lecture on psychology, delivered by either a male or female lecturer, after which they were asked to evaluate their experience and instructor personality characteristics. To ensure consistency across content, tone, delivery, environment, and overall appearance, photorealistic 3D avatars were used to deliver the lectures. Only gender as a factor was manipulated. Given the racial representation in the region, a total of four videos were developed representing males (n = 317) and females (n = 354) of White and South Asian race. Overall, male instructors scored significantly higher in variables representing personality characteristics such as enthusiasm and expressiveness compared to female instructors. Participants did not however view male and female instructors to be different in terms of presentation and subject knowledge. Findings related to facilitating learning suggest that male instructors were perceived to have made instructions more interesting, kept participants' attention for longer, and were more interesting compared to female instructors. In terms of engagement, male instructors were perceived to be more expressive, enthusiastic, and entertaining, compared to female instructors. Given the experimental design, these findings can clearly be attributed to gender bias, which is also in line with previous research. With an underrepresented sample, an online platform delivery, and inclusion of multiple races, these findings significantly add value to the current literature regarding gender stereotypes in higher education. The results are even more concerning as they provide strong evidence of gender bias which may contribute to subconscious discrimination against women academics in the region.
How to promote preservice teachers’ reflections through critical incident training
Authors: Anselmann Veronika
Published: July 2023

Introduction

This study with a pre-post design reports the results of training developed from the framework of reflective practice and the critical incident technique (CIT) for teacher education.

Methods

Fifty-three preservice teachers participated in either online or face-to-face training, with the aim of determining if the training sufficiently improved their reflection abilities. To this purpose, an online questionnaire with validated scales on educational satisfaction, reflection abilities, and learning logs were used. The data were analyzed using descriptive statistical analysis and t-tests, as well as qualitative data analysis.

Results

The results show that the students significantly improved their teaching reflection abilities after participating in the training.

Discussion

Giving preservice teachers the opportunity to reflect on their own experiences is thus an appropriate way to foster their reflection abilities.
The proteome and phosphoproteome of circulating extracellular vesicle-enriched preparations are associated with characteristic clinical features in type 1 diabetes
Authors: Casu Anna , Nunez Lopez Yury O. , Yu Gongxin , Clifford Christopher , Bilal Anika , Petrilli Alejandra M. , Cornnell Heather , Carnero Elvis Alvarez , Bhatheja Ananya , Corbin Karen D. , Iliuk Anton , Maahs David M. , Pratley Richard E.
Published: July 2023

Introduction

There are no validated clinical or laboratory biomarkers to identify and differentiate endotypes of type 1 diabetes (T1D) or the risk of progression to chronic complications. Extracellular vesicles (EVs) have been studied as biomarkers in several different disease states but have not been well studied in T1D.

Methods

As the initial step towards circulating biomarker identification in T1D, this pilot study aimed to provide an initial characterization of the proteomic and phosphoproteomic landscape of circulating EV-enriched preparations in participants with established T1D (N=10) and healthy normal volunteers (Controls) (N=7) (NCT03379792) carefully matched by age, race/ethnicity, sex, and BMI. EV-enriched preparations were obtained using EVtrap® technology. Proteins were identified and quantified by LC-MS analysis. Differential abundance and coexpression network (WGCNA), and pathway enrichment analyses were implemented.

Results

The detected proteins and phosphoproteins were enriched (75%) in exosomal proteins cataloged in the ExoCarta database. A total of 181 proteins and 8 phosphoproteins were differentially abundant in participants with T1D compared to controls, including some well-known EVproteins (i.e., CD63, RAB14, BSG, LAMP2, and EZR). Enrichment analyses of differentially abundant proteins and phosphoproteins of EV-enriched preparations identified associations with neutrophil, platelet, and immune response functions, as well as prion protein aggregation. Downregulated proteins were involved in MHC class II signaling and the regulation of monocyte differentiation. Potential key roles in T1D for C1q, plasminogen, IL6ST, CD40, HLA-DQB1, HLA-DRB1, CD74, NUCB1, and SAP, are highlighted. Remarkably, WGCNA uncovered two protein modules significantly associated with pancreas size, which may be implicated in the pathogenesis of T1D. Similarly, these modules showed significant enrichment for membrane compartments, processes associated with inflammation and the immune response, and regulation of viral processes, among others.

Discussion

This study demonstrates the potential of proteomic and phosphoproteomic signatures of EV-enriched preparations to provide insight into the pathobiology of T1D. The WGCNA analysis could be a powerful tool to discriminate signatures associated with different pathobiological components of the disease.
Response capability evaluation model of electric vehicle aggregator based on evolutionary game and response anticipation
Authors: Xu Xiangchu , Mi Zengqiang , Zhan Zewei , Ji Ling
Published: July 2023

Accurately quantitative evaluation of the response capability of electric vehicle aggregator (EVA), i.e., the adjustable range of power, is the premise and basis of its participation in the demand response (DR). In response to the current EVA’s response capability evaluation, ignoring the autonomy of EV decision-making behavior may lead to overly idealized evaluation results, as well as the problem of evaluating only from a single time scale. To this end, this paper proposes a response capability evaluation model of EVA based on evolutionary game and response anticipation. Based on the physical constraints of EVs and their willingness to discharge, response capability evaluation models are constructed for individual EVs of different response types. Considering the autonomy of decision-making behavior of EVs, an evolutionary game model with multi-strategy sets of EVs is constructed. Based on the idea of response anticipation, a regulation strategy is proposed for EVA to achieve the dynamic update of EVA’s response capability. The proposed model is verified to be able to accurately evaluate the EVA’s response capability through simulation examples, and the EVA response capability evaluation is extended from a single time scale to multiple time scales. The evaluation results can be used as the basis for EVA to participate in the electricity market bidding.
A model for identifying the feeder-transformer relationship in distribution grids using a data-driven machine-learning algorithm
Authors: Gao Yongmin , Kang Bing , Xiao Hui , Wang Zongyao , Ding Guili , Xu Zhihao , Liu Chuan , Wang Daxing , Li Yutong
Published: July 2023

With the increasing demand for reliable power supply and the widespread integration of distributed energy sources, the topology of distribution networks is subject to frequent changes. Consequently, the dynamic alterations in the connection relationships between distribution transformers and feeders occur frequently, and these changes are not accurately monitored by grid companies in real-time. In this paper, we present a data-driven machine learning approach for identifying the feeder-transformer relationship in distribution networks. Initially, we preprocess the collected three-phase voltage magnitude data of distribution transformers, addressing data quality and enhancing usability through three-phase voltage normalization. Subsequently, we derive the correlation coefficient calculations between distribution transformers, as well as between distribution transformers and feeders. To tackle the challenging task of determining the correlation coefficient threshold, we propose a multi-feature fusion approach. We extracted additional features from the feeders and combined them with the correlation coefficients to create a feature matrix. Machine learning algorithms were then applied to calculate the results. Through experimentation on a real distribution network in Jiangxi province, we demonstrated the effectiveness of the proposed method. When compared to other approaches, our method achieved outstanding results with an F1 score of 0.977, indicating high precision and recall. The precision value was 0.973 and the recall value was 0.981. Importantly, our method eliminates the need for additional measurement installations, as the required data can be obtained using existing collection devices. This significantly reduces the application cost associated with implementing our approach.
FUN Azores: a FUNctional trait database for the meio-, macro-, and megafauna from the Azores Marine Park (Mid-Atlantic Ridge)
Authors: Campanyà-Llovet Neus , Bates Amanda E. , Cuvelier Daphne , Giacomello Eva , Catarino Diana , Gooday Andrew J. , Berning Björn , Figuerola Blanca , Malaquias Manuel A. E. , Moura Carlos J. , Xavier Joana R. , Sutton Tracey T. , Fauconnet Laurence , Ramalho Sofia P. , Neves Bárbara de Moura , Menezes Gui M. , Horton Tammy , Gebruk Andrey V. , Minin Kirill , Bried Joël , Molodtsova Tina , Silva Mónica A. , Dilman Anna , Kremenetskaia Antonina , Costa Eudriano F. S. , Clarke Jameson , Martins Helen R. , Pham Christopher K. , Carreiro-Silva Marina , Colaço Ana
Published: July 2023

Trait-based approaches that complement taxonomy-based studies have increased in popularity among the scientific community over the last decades. The collection of biological and ecological characteristics of species (i.e., traits) provides insight into species and ecosystem vulnerability to environmental and anthropogenic changes, as well as ecosystem functioning. Here, we present the FUN Azores trait database, describe our approach, evaluate its scope, compare it to other marine trait databases, and explore the spatial distribution of its traits with “functional maps.” While most of the available trait databases to date contain essential information to understand the functional diversity of a taxonomic or functional group, our ecosystem-based approach provides a comprehensive assessment of diverse fauna (i.e., meio-, macro-, and megafauna) from benthic and pelagic environments in the Azores Marine Park; including ridges, seamounts, hydrothermal vents, and the overlying water column. We used a collaborative approach involving 30 researchers with different expertise to develop the FUN Azores database, which contains compiled data on 14 traits representing morphological, behavioral, and life history characteristics for 1,210 species across 10 phyla. The “functional maps” show a distinct distribution of the two most common size classes, suggesting different communities with different functionalities. The following traits had the best scoring coverage (i.e., >95% of the species scored): maximum body size, body form, skeleton material, feeding structure, motility, environmental position, substratum affinity, distribution, and depth range; while traits related to species behavior (e.g., sociability or aggregation tendencies) and life history (e.g., developmental mechanism) had lower scoring coverage, highlighting the need for further research to fill these knowledge gaps. We found a larger number of species in the benthic compared to the pelagic environment and differing species composition between areas within the Azores Marine Park resulting from varying biodiversity, ecosystem types, sampling effort, and methodologies used. The FUN Azores database will foster and facilitate trait-based approaches in the area, develop a framework for expansion of cross-ecosystem and cross-taxa trait databases elsewhere, and improve our ecological understanding of the Azores Marine Park and its conservation requirements.
Drought characteristics and their impacts on vegetation net primary productivity in the subtropical China
Authors: Ye Qing , Feng Wenzhong , Jiao Gengying , Deng Wenping
Published: July 2023

Drought is one of the main factors limiting forest productivity, and thus greatly affects the carbon sink capacity of forests. Here we first chose two drought indices including standardized precipitation evapotranspiration index (SPEI) and self-calibrating Palmer drought severity index (scPDSI) to reflect and analyze the spatiotemporal patterns of drought in the subtropical China. Then, the validated CASA (Carnegie-Amer-Stanford Approach) model was applied to estimate forest net primary productivity (NPP) and further quantify the contributions of drought events and their characteristics on forest NPP. The results showed that drought events during 2000–2015 have resulted in a mean decline of forest NPP of 7.2%. Moderate or severe drought events reduced NPP more significantly than extremely severe drought events. In addition, there was 1–2 years of lagging in the NPP responses to drought, and the lagging time varied with forest types. Our study suggests that forest managers and local governments should pay more attention to the places with moderate and severe drought events, and take measures to avoid NPP decline within the 2 years after drought. Our study also provides data support for further identifying the contribution of drought to ecosystem carbon fluxes in the subtropical China.
Interspecies trophic niche differences and spatial–temporal adaptations found in Cultrinae fishes
Authors: Yang Tingyue , Yang Shufan , Yu Dan , Wang Chunling , Shang Kunyu , Liu Huanzhang
Published: July 2023

It has been debated whether interspecies niche differences may follow niche conservatism, whether niches are becoming specialists, whether generalists and specialists are maintained in a balance, and how the realized niche may adapt to local or temporal environments. In the present study, by using stable isotope analysis to evaluate the trophic niche of seven Cultrinae species, we investigated niche conservatism among these species from 10 sites of the Yangtze River by testing the Mantel test of trophic niche variables [trophic position (TP), δ13C, and trophic niche breadth]. We also comprehensively investigated the fundamental niche differences as well as spatial and temporal adaptations of the realized niche of these seven Cultrinae species by calculating trophic niche breadths, overlap, and TP. The results showed that TP and fundamental trophic niche breadth exhibited phylogenetic conservatism, while the fundamental trophic niche breadth of the three Hemicultrine species tended to become generalists and four Cultrine species tended to become specialists. Moreover, the realized trophic niche of the same species would exhibit different adaptation at different sites as well as in different seasons. In the wet season, trophic niche breadths of the seven species were significantly larger than that in the dry season with great overlaps between species, while in the dry season, trophic niche separation was found among the seven species due to competitive exclusion of niches. We believe that these findings will contribute to future theoretical and empirical niche investigations.
High-efficiency fungal pathogen intervention for seed protection: new utility of long-chain alkyl gallates as heat-sensitizing agents
Authors: Kim Jong H. , Chan Kathleen L. , Hart-Cooper William M. , Palumbo Jeffrey D. , Orts William J.
Published: July 2023

Control of food-contaminating fungi, especially pathogens that produce mycotoxins, is problematic since effective method for intervening fungal infection on food crops is often limited. Generally Regarded As Safe (GRAS) chemicals, such as natural compounds or their structural derivatives, can be developed as antimicrobial agents for sustainable food/crop production. This study identified that long-chain alkyl gallates, i.e., octyl-, nonyl-, and decyl gallates (OG (octyl 3,4,5-trihydroxybenzoic acid), NG, DG), can function as heat-sensitizing agents that effectively prevent fungal contamination. Out of twenty-eight candidate compounds and six conventional antifungal agents examined, the heat-sensitizing capacity was unique to the long-chain alkyl gallates, where OG exhibited the highest activity, followed by DG and NG. Since OG is a GRAS compound classified by the United States Food and Drug Administration (FDA), further in vitro antifungal studies were performed using OG. When OG and mild heat (57.5°C) were co-administered for 90 seconds, the treatment achieved > 99.999% fungal death (> 5 log reduction). Application of either treatment alone was significantly less effective at reducing fungal survival. Of note, co-application of OG (3 mM) and mild heat (50°C) for 20 minutes completely prevented the survival of aflatoxigenic Aspergillus flavus contaminating crop seeds (Brassica rapa Pekinensis), while seed germination rate was unaffected. Heat-sensitization was also determined in selected bacterial strains (Escherichia coli, Agrobacterium tumefaciens). Altogether, OG is an effective heat-sensitizing agent for control of microbial pathogens. OG-mediated heat sensitization will improve the efficacy of antimicrobial practices, achieving safe, rapid, and cost-effective pathogen control in agriculture/food industry settings.
A simple sequence repeats marker of disease resistance in shrimp Litopenaeus vannamei and its application in selective breeding
Authors: Yin Bin , Wang Haiyang , Weng Shaoping , Li Sedong , He Jianguo , Li Chaozheng
Published: July 2023

The polymorphism of the simple sequence repeat (SSR) in the 5′ untranslated coding region (5′-UTR) of the antiviral gene IRF (LvIRF) has been shown to be implicated in the resistance to viral pathogens in shrimp Litopenaeus vannamei (L. vannamei). In this study, we explored the potential of this (CT)n-SSR marker in disease resistance breeding and the hereditary property of disease resistance traits in offspring. From 2018 to 2021, eight populations were generated through crossbreeding by selecting individuals according to microsatellite genotyping. Our results demonstrated that shrimp with the shorter (CT)n repeat exhibited higher resistance to white spot syndrome virus (WSSV) or Decapod iridescent virus 1 (DIV1); meanwhile, these resistance traits could be inherited in offspring. Interestingly, we observed that the longer (CT)n repeats were associated with bacterial resistance traits. Accordingly, shrimp with longer (CT)n repeats exhibited higher tolerance to Vibrio parahaemolyticus infection. Taken together, these results indicate that the single (CT)n-SSR marker could be used to selective breeding for both resistance to virus and bacteria in shrimps.
Meta-analysis of heritability estimates and genome-wide association for tick-borne haemoparasites in African cattle
Authors: Riggio Valentina , Madder Maxime , Labuschagne Michel , Callaby Rebecca , Zhao Rongrong , Djikeng Appolinaire , Fourie Josephus , Prendergast James G. D. , Morrison Liam J.
Published: July 2023

The control of tick-borne haemoparasites in cattle largely relies on the use of acaricide drugs against the tick vectors, with some vaccination also being used against selected pathogens. These interventions can be difficult in Africa, where accessibility and cost of vaccines can be issues, and the increasing resistance of tick vectors to the widely used acaricides is a complication to disease control. A potential complementary control strategy could be the exploitation of any natural host genetic resistance to the pathogens. However, there are currently very few estimates of the extent of host resistance to tick-borne haemoparasites, and a significant contributing factor to this knowledge gap is likely to be the difficulty of collecting appropriate samples and data in the smallholder systems that predominate livestock production in low- and middle-income countries, particularly at scale. In this study, we have estimated the heritability for the presence/absence of several important haemoparasite species (including Anaplasma marginale, Babesia bigemina, Babesia bovis, and Ehrlichia ruminantium), as well as for relevant traits such as body weight and body condition score (BCS), in 1,694 cattle from four African countries (Burkina Faso, Ghana, Nigeria, and Tanzania). Heritability estimates within countries were mostly not significant, ranging from 0.05 to 0.84 across traits and countries, with standard errors between 0.07 and 0.91. However, the weighted mean of heritability estimates was moderate and significant for body weight and BCS (0.40 and 0.49, respectively), with significant heritabilities also observed for the presence of A. marginale (0.16) and E. ruminantium (0.19). In a meta-analysis of genome-wide association studies (GWAS) for these traits, two peaks were identified as reaching the suggestive significance threshold (p < 1.91 × 10−7 and p < 1.89 × 10−7, respectively): one on chromosome 24 for BCS and one on chromosome 8 for the E. ruminantium infection status. These findings indicate that there is likely to be a genetic basis that contributes to pathogen presence/absence for tick-borne haemoparasite species, which could potentially be exploited to improve cattle resistance in Africa to the economically important diseases caused by these pathogens.
Characterization of the TRPV6 calcium channel-specific phenotype by RNA-seq in castration-resistant human prostate cancer cells
Authors: Cordier Clément , Haustrate Aurélien , Prevarskaya Natalia , Lehen’kyi V’yacheslav
Published: July 2023

Background: Transient receptor potential vanilloid subfamily member 6 (TRPV6), a highly calcium-selective channel, has been shown to play a significant role in calcium homeostasis and to participate both in vitro and in vivo in growth, cell survival, and drug resistance of prostate cancer. Its role and the corresponding calcium-dependent pathways were mainly studied in hormone-dependent human prostate cancer cell lines, often used as a model of early-stage prostate cancers. The goal of the present study was to describe the TRPV6-specific phenotype and signaling pathways it is involved in, using castration-resistant prostate cancer cell lines.

Methods: RNA sequencing (RNA-seq) was used to study the gene expression impacted by TRPV6 using PC3Mtrpv6−/−versus PC3Mtrpv6+/+ and its derivative PC3M-luc-C6trpv6+/+ cell line in its native and TRPV6 overexpressed form. In addition to the whole-cell RNA sequencing, immunoblotting, quantitative PCR, and calcium imaging were used to validate trpv6 gene status and functional consequences, in both trpv6-/- and TRPV6 overexpression cell lines.

Results:trpv6-/- status was validated using both immunoblotting and quantitative PCR, and the functional consequences of either trpv6 gene deletion or TRPV6 overexpression were shown using calcium imaging. RNA-seq analysis demonstrated that the calcium channel TRPV6, being a crucial player of calcium signaling, significantly impacts the expression of genes involved in cancer progression, such as cell cycle regulation, chemotaxis, migration, invasion, apoptosis, ferroptosis as well as drug resistance, and extracellular matrix (ECM) re-organization.

Conclusion: Our data suggest that the trpv6 gene is involved in and regulates multiple pathways related to tumor progression and drug resistance in castration-resistant prostate cancer cells.
Functional reprogramming of peripheral blood monocytes by soluble mediators in patients with pancreatic cancer and intraductal papillary mucinous neoplasms
Authors: Eckhoff Austin M. , Brown Michael C. , Landa Karenia , Naqvi Ibtehaj , Holl Eda K. , Boczkowski David , Fletcher Ashley , Rhodin Kristen E. , Giang Minh Huy , Sullenger Bruce , Beasley Georgia M. , Allen Peter J. , Nair Smita K.
Published: July 2023

Background

Monocytes and monocyte-derived tumor infiltrating cells have been implicated in the immunosuppression and immune evasion associated with pancreatic adenocarcinoma (PDAC). Yet, precisely how monocytes in the periphery and tumor microenvironment in patients with intraductal papillary mucinous neoplasm (IPMN), a precursor lesion to PDAC, change during disease progression has not been defined. Here we functionally profiled the peripheral immune system and characterized the tumor microenvironment of patients with both IPMN and PDAC. We also tested if sera from patients with IPMN and PDAC functionally reprogram monocytes relative to that of healthy donors.

Methods

Pancreatic tissue and peripheral blood were collected at the time of resection from 16 patients with IPMN and 32 patients with PDAC. Peripheral blood and pancreatic tissue/tumor were immunophenotyped using flow cytometry. Whole blood was plated and incubated with R848 (a TLR 7/8 agonist) or LPS (a TLR4 agonist) for 6 hours and TNF expression in monocytes was measured by flow cytometry to measure monocyte activation. To test if TLR sensitivity is determined by factors in patient sera, we preconditioned healthy donor monocytes in serum from PDAC (n=23), IPMN (n=15), or age-matched healthy donors (n=10) followed by in vitro stimulation with R848 or LPS and multiplex cytokine measurements in the supernatant.

Results

TNF expression in R848-stimulated peripheral blood monocytes was higher in patients with low grade vs high grade IPMN (65% vs 32%, p = 0.03) and stage 1 vs stage 2/3 PDAC (58% vs 42%, p = 0.03), this was not observed after LPS stimulation. TLR activation correlated with increasing grade of dysplasia from low grade IPMN to high grade IPMN. Serum from patients with IPMN and PDAC recapitulated suppression of TNF induction after R848 stimulation in naïve, healthy donor monocytes.

Conclusion

Peripheral blood monocyte TNF secretion inversely correlates with the degree of dysplasia in IPMN and cancer stage in PDAC, suggesting innate immune reprogramming as IPMNs progress to invasive disease. These effects are, at least in part, mediated by soluble mediators in sera.
Clinical and immunological spectra of human cutaneous leishmaniasis in North Africa and French Guiana
Authors: Saidi Nasreddine , Blaizot Romain , Prévot Ghislaine , Aoun Karim , Demar Magalie , Cazenave Pierre André , Bouratbine Aida , Pied Sylviane
Published: July 2023

Cutaneous leishmaniasis (CL) caused by infection with the parasite Leishmania exhibits a large spectrum of clinical manifestations ranging from single healing to severe chronic lesions with the manifestation of resistance or not to treatment. Depending on the specie and multiple environmental parameters, the evolution of lesions is determined by a complex interaction between parasite factors and the early immune responses triggered, including innate and adaptive mechanisms. Moreover, lesion resolution requires parasite control as well as modulation of the pathologic local inflammation responses and the initiation of wound healing responses. Here, we have summarized recent advances in understanding the in situ immune response to cutaneous leishmaniasis: i) in North Africa caused by Leishmania (L.) major, L. tropica, and L. infantum, which caused in most cases localized autoresolutives forms, and ii) in French Guiana resulting from L. guyanensis and L. braziliensis, two of the most prevalent strains that may induce potentially mucosal forms of the disease. This review will allow a better understanding of local immune parameters, including cellular and cytokines release in the lesion, that controls infection and/or protect against the pathogenesis in new world compared to old world CL.
Chitinase-3-like 1 regulates TH2 cells, TFH cells and IgE responses to helminth infection
Authors: Curtiss Miranda L. , Rosenberg Alexander F. , Scharer Christopher D. , Mousseau Betty , Benavides Natalia A. Ballesteros , Bradley John E. , León Beatriz , Steele Chad , Randall Troy D. , Lund Frances E.
Published: July 2023

Introduction

Data from patient cohorts and mouse models of atopic dermatitis, food allergy and asthma strongly support a role for chitinase-3-like-1 protein (CHI3L1) in allergic disease.

Methods

To address whether Chi3l1 also contributes to TH2 responses following nematode infection, we infected Chi3l1-/- mice with Heligmosomoides polygyrus (Hp) and analyzed T cell responses.

Results

As anticipated, we observed impaired TH2 responses in Hp-infected Chi3l1-/- mice. However, we also found that T cell intrinsic expression of Chi3l1 was required for ICOS upregulation following activation of naïve CD4 T cells and was necessary for the development of the IL-4+ TFH subset, which supports germinal center B cell reactions and IgE responses. We also observed roles for Chi3l1 in TFH, germinal center B cell, and IgE responses to alum-adjuvanted vaccination. While Chi3l1 was critical for IgE humoral responses it was not required for vaccine or infection-induced IgG1 responses.

Discussion

These results suggest that Chi3l1 modulates IgE responses, which are known to be highly dependent on IL-4-producing TFH cells.
Development of tolerance to chemokine receptor antagonists: current paradigms and the need for further investigation
Authors: Grudzien Patrick , Neufeld Henry , Ebe Eyenga Mbasogo , Gaponenko Vadim
Published: July 2023

Chemokine G-protein coupled receptors are validated drug targets for many diseases, including cancer, neurological, and inflammatory disorders. Despite much time and effort spent on therapeutic development, very few chemokine receptor antagonists are approved for clinical use. Among potential reasons for the slow progress in developing chemokine receptor inhibitors, antagonist tolerance, a progressive reduction in drug efficacy after repeated administration, is likely to play a key role. The mechanisms leading to antagonist tolerance remain poorly understood. In many cases, antagonist tolerance is accompanied by increased receptor concentration on the cell surface after prolonged exposure to chemokine receptor antagonists. This points to a possible role of altered receptor internalization and presentation on the cell surface, as has been shown for agonist (primarily opioid) tolerance. In addition, examples of antagonist tolerance in the context of other G-protein coupled receptors suggest the involvement of noncanonical signal transduction in opposing the effects of the antagonists. In this review, we summarize the available progress and challenges in therapeutic development of chemokine receptor antagonists, describe the available knowledge about antagonist tolerance, and propose new avenues for future investigation of this important phenomenon. Furthermore, we highlight the modern methodologies that have the potential to reveal novel mechanisms leading to antagonist tolerance and to propel the field forward by advancing the development of potent “tolerance-free” antagonists of chemokine receptors.
The role of N-glycosylation in B-cell biology and IgG activity. The aspects of autoimmunity and anti-inflammatory therapy
Authors: Trzos Sara , Link-Lenczowski Paweł , Pocheć Ewa
Published: July 2023

The immune system is strictly regulated by glycosylation through the addition of highly diverse and dynamically changing sugar structures (glycans) to the majority of immune cell receptors. Although knowledge in the field of glycoimmunology is still limited, numerous studies point to the key role of glycosylation in maintaining homeostasis, but also in reflecting its disruption. Changes in oligosaccharide patterns can lead to impairment of both innate and acquired immune responses, with important implications in the pathogenesis of diseases, including autoimmunity. B cells appear to be unique within the immune system, since they exhibit both innate and adaptive immune activity. B cell surface is rich in glycosylated proteins and lectins which recognise glycosylated ligands on other cells. Glycans are important in the development, selection, and maturation of B cells. Changes in sialylation and fucosylation of cell surface proteins affect B cell signal transduction through BCRs, CD22 inhibitory coreceptor and Siglec-G. Plasmocytes, as the final stage of B cell differentiation, produce and secrete immunoglobulins (Igs), of which IgGs are the most abundantN-glycosylated proteins in human serum with the conservedN-glycosylation site at Asn297.N-oligosaccharide composition of the IgG Fc region affects its secretion, structure, half-life and effector functions (ADCC, CDC). IgGN-glycosylation undergoes little change during homeostasis, and may gradually be modified with age and during ongoing inflammatory processes. Hyperactivated B lymphocytes secrete autoreactive antibodies responsible for the development of autoimmunity. The altered profile of IgGN-glycans contributes to disease progression and remission and is sensitive to the application of therapeutic substances and immunosuppressive agents. In this review, we focus on the role ofN-glycans in B-cell biology and IgG activity, the rearrangement of IgG oligosaccharides in aging, autoimmunity and immunosuppressive therapy.
The landscape of the immunoglobulin repertoire in endemic pemphigus foliaceus
Authors: Calonga-Solís Verónica , Olbrich Michael , Ott Fabian , Adelman Cipolla Gabriel , Malheiros Danielle , Künstner Axel , Farias Ticiana D.J. , Camargo Carolina M. , Petzl-Erler Maria Luiza , Busch Hauke , Fähnrich Anke , Augusto Danillo G.
Published: July 2023

Introduction

Primarily driven by autoreactive B cells, pemphigus foliaceus (PF) is an uncommon autoimmune blistering skin disease of sporadic occurrence worldwide. However, PF reaches a prevalence of 3% in the endemic areas of Brazil, the highest ever registered for any autoimmune disease, which indicates environmental factors influencing the immune response in susceptible individuals. We aimed to provide insights into the immune repertoire of patients with PF living in the endemic region of the disease, compared to healthy individuals from the endemic region and a non-endemic area.

Methods

We characterized the B-cell repertoire in i) nontreated patients (n=5); ii) patients under immunosuppressive treatment (n=5); iii) patients in remission without treatment (n=6); and two control groups iv) from the endemic (n=6) and v) non-endemic areas in Brazil (n=4). We used total RNA extracted from peripheral blood mononuclear cells and performed a comprehensive characterization of the variable region of immunoglobulin heavy chain (IGH) in IgG and IgM using next-generation sequencing.

Results

Compared to individuals from a different area, we observed remarkably lower clonotype diversity in the B-cell immune repertoire of patients and controls from the endemic area (p < 0.02), suggesting that the immune repertoire in the endemic area is under geographically specific and intense environmental pressure. Moreover, we observed longer CDR3 sequences in patients, and we identified differential disease-specific usage of IGHV segments, including increased IGHV3-30 and decreased IGHV3-23 in patients with active disease (p < 0.04). Finally, our robust network analysis discovered clusters of CDR3 sequences uniquely observed in patients with PF.

Discussion

Our results indicate that environmental factors, in addition to disease state, impact the characteristics of the repertoire. Our findings can be applied to further investigation of the environmental factors that trigger pemphigus and expand the knowledge for identifying new targeted and more effective therapies.
Associations of complete blood cell count-derived inflammatory biomarkers with asthma and mortality in adults: a population-based study
Authors: Ke Junhua , Qiu Fushan , Fan Wenxi , Wei Songqing
Published: July 2023

Objective

This study aims to assess the associations of complete blood cell count (CBC)-derived inflammatory biomarkers with the prevalence of asthma and mortality.

Methods

Data was collected from the 1999-2018 National Health and Nutrition Examination Survey (NHANES). Mortality was identified using the National Death Index until December 31, 2019. The study analyzed the relationship between CBC-derived inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic inflammatory response index (SIRI), and systemic immune-inflammation index (SII), and the prevalence of asthma using multiple logistic regressions. To assess the significance of CBC-derived inflammatory biomarkers in predicting all-cause and respiratory disease mortality in asthma patients, Cox proportional regressions and the random survival forest (RSF) analysis were utilized.

Results

A total of 48,305 participants were included, with a mean age of 47.27 ± 0.18 years and 49.44% male. Among them, 6,403 participants had asthma, with a prevalence of 13.28%. The all-cause and respiratory disease deaths at a median follow-up of 8.2 (4.5, 12.8) years were 929 and 137 respectively. After adjusting for confounders, the prevalence of asthma was found to be positively associated with NLR, PLR, MLR, SIRI and SII. Compared to the lowest quartile, the highest quartile of NLR (HR=1.765 [1.378-2.262]), MLR (HR=1.717 [1.316-2.241]), SIRI (HR=1.796 [1.353-2.383]) and SII (HR=1.432 [1.141-1.797]) were associated with an increased risk of all-cause mortality. These associations were more pronounced in respiratory disease mortality of asthma patients. RSF analysis showed that MLR had the highest predictive value for all-cause and respiratory disease mortality in adults with asthma. The sensitivity analysis demonstrated the stability of our results.

Conclusion

The findings suggest that CBC-derived inflammatory biomarkers are associated with a higher risk of all-cause and respiratory disease mortality in adults with asthma.