bluuebunny/crossref_metadata_2025 huggingface dataset:
Can positive welfare counterbalance negative and can net welfare be assessed?
Authors: Broom Donald M.
Published: June 2023

The absence of poor welfare is important for welfare to be good, but measures of good welfare are of great value in welfare assessment. Assessors of the welfare of individuals need to know the overall balance of good and poor. Direct behavioural measures and measures of physiology, such as oxytocin concentration, together with experimental studies of motivation, help in evaluating whether positive or negative components of welfare are prevailing in a given situation. Studies of humans and other animal species are described. While there are few detailed comprehensive studies measuring positive and negative welfare in the same individuals, examples are given of overall measurements of consequences when there could be positive and negative effects. Measures of net welfare, when positive and negative components have been resolved, are described. It is concluded that good welfare can often counterbalance poor welfare but does not do so in all circumstances.
Comparison of phasor analysis and biexponential decay curve fitting of autofluorescence lifetime imaging data for machine learning prediction of cellular phenotypes
Authors: Hu Linghao , Ter Hofstede Blanche , Sharma Dhavan , Zhao Feng , Walsh Alex J.
Published: June 2023

Introduction: Autofluorescence imaging of the coenzymes reduced nicotinamide (phosphate) dinucleotide (NAD(P)H) and oxidized flavin adenine dinucleotide (FAD) provides a label-free method to detect cellular metabolism and phenotypes. Time-domain fluorescence lifetime data can be analyzed by exponential decay fitting to extract fluorescence lifetimes or by a fit-free phasor transformation to compute phasor coordinates.

Methods: Here, fluorescence lifetime data analysis by biexponential decay curve fitting is compared with phasor coordinate analysis as input data to machine learning models to predict cell phenotypes. Glycolysis and oxidative phosphorylation of MCF7 breast cancer cells were chemically inhibited with 2-deoxy-d-glucose and sodium cyanide, respectively; and fluorescence lifetime images of NAD(P)H and FAD were obtained using a multiphoton microscope.

Results: Machine learning algorithms built from either the extracted lifetime values or phasor coordinates predict MCF7 metabolism with a high accuracy (∼88%). Similarly, fluorescence lifetime images of M0, M1, and M2 macrophages were acquired and analyzed by decay fitting and phasor analysis. Machine learning models trained with features from curve fitting discriminate different macrophage phenotypes with improved performance over models trained using only phasor coordinates.

Discussion: Altogether, the results demonstrate that both curve fitting and phasor analysis of autofluorescence lifetime images can be used in machine learning models for classification of cell phenotype from the lifetime data.
Combining biomechanical stimulation and chronobiology: a novel approach for augmented chondrogenesis?
Authors: Vágó Judit , Takács Roland , Kovács Patrik , Hajdú Tibor , van der Veen Daan R. , Matta Csaba
Published: June 2023

The unique structure and composition of articular cartilage is critical for its physiological function. However, this architecture may get disrupted by degeneration or trauma. Due to the low intrinsic regeneration properties of the tissue, the healing response is generally poor. Low-grade inflammation in patients with osteoarthritis advances cartilage degradation, resulting in pain, immobility, and reduced quality of life. Generating neocartilage using advanced tissue engineering approaches may address these limitations. The biocompatible microenvironment that is suitable for cartilage regeneration may not only rely on cells and scaffolds, but also on the spatial and temporal features of biomechanics. Cell-autonomous biological clocks that generate circadian rhythms in chondrocytes are generally accepted to be indispensable for normal cartilage homeostasis. While the molecular details of the circadian clockwork are increasingly well understood at the cellular level, the mechanisms that enable clock entrainment by biomechanical signals, which are highly relevant in cartilage, are still largely unknown. This narrative review outlines the role of the biomechanical microenvironment to advance cartilage tissue engineering via entraining the molecular circadian clockwork, and highlights how application of this concept may enhance the development and successful translation of biomechanically relevant tissue engineering interventions.
RNA-binding proteins that are highly expressed and enriched in healthy cartilage but suppressed in osteoarthritis
Authors: Swahn Hannah , Olmer Merissa , Lotz Martin K.
Published: June 2023

Objectives: RNA-binding proteins (RBPs) have diverse and essential biological functions, but their role in cartilage health and disease is largely unknown. The objectives of this study were (i) map the global landscape of RBPs expressed and enriched in healthy cartilage and dysregulated in osteoarthritis (OA); (ii) prioritize RBPs for their potential role in cartilage and in OA pathogenesis and as therapeutic targets.

Methods: Our published bulk RNA-sequencing (RNA-seq) data of healthy and OA human cartilage, and a census of 1,542 RBPs were utilized to identify RBPs that are expressed in healthy cartilage and differentially expressed (DE) in OA. Next, our comparison of healthy cartilage RNA-seq data to 37 transcriptomes in the Genotype-Tissue Expression (GTEx) database was used to determine RBPs that are enriched in cartilage. Finally, expression of RBPs was analyzed in our single cell RNA-sequencing (scRNA-seq) data from healthy and OA human cartilage.

Results: Expression of RBPs was higher than nonRBPs in healthy cartilage. In OA cartilage, 188 RBPs were differentially expressed, with a greater proportion downregulated. Ribosome biogenesis was enriched in the upregulated RBPs, while splicing and transport were enriched in the downregulated. To further prioritize RBPs, we selected the top 10% expressed RBPs in healthy cartilage and those that were cartilage-enriched according to GTEx. Intersecting these criteria, we identified Tetrachlorodibenzodioxin (TCDD) Inducible Poly (ADP-Ribose) Polymerase (TIPARP) as a candidate RBP. TIPARP was downregulated in OA. scRNA-seq data revealed TIPARP was most significantly downregulated in the “pathogenic cluster”.

Conclusion: Our global analyses reveal expression patterns of RBPs in healthy and OA cartilage. We also identified TIPARP and other RBPs as novel mediators in OA pathogenesis and as potential therapeutic targets.
No causal genetic relationships between atrial fibrillation and vascular dementia: A bidirectional Mendelian randomization study
Authors: Gao Ya-fang , Jin Tian-yu , Chen Yan , Ding Ya-hui
Published: June 2023

Background

Numerous observational studies have suggested that atrial fibrillation (AF) was associated with an increased risk of vascular dementia (VaD). However, the causal genetic relationships between AF and VaD remains unclear. To evaluate the effect of AF on VaD, we performed the Mendelian randomization (MR) analysis to investigate the causal genetic relationships between AF and VaD.

Methods

The bidirectional MR analysis was conducted to explore the causal relationships between exposure and disease. We applied a series of quality assessments to select significantly and independently single nucleotide polymorphisms (SNPs) from publicly available large-scale genome-wide association studies (GWAS) databases. Three methods [Inverse variance weighted method (IVW), MR-Egger method, and weighted median (WM)method] were used to derive MR estimates. In order to ensure reliable MR results, sensitivity analyses were performed to evaluate the horizontal pleiotropy and heterogeneity.

Results

Our MR analyses revealed no significant genetic relationships between AF and the risk of VaD (IVW: OR =  1.10, 95%CI = 0.95–1.28, P = 0.20). In the reverse direction analysis, there was no evidence to support a significant genetic relationship of VaD with AF risk (IVW: OR =  1.00, 95% CI = 0.99–1.01, P = 0.52). Consistent results were obtained using different MR methods. Sensitivity analyses suggested no significant horizontal pleiotropy and heterogeneity in the study.

Conclusion

This MR analysis did not provide evidence to support the causal genetic relationships between AF on VaD risk and the causal effect of VaD on AF risk.
Crustal structure and geodynamics of the eastern Qilian orogenic belt, NE margin of the Qinghai-Tibet plateau, revealed by teleseismic receiver function
Authors: Cheng Yongzhi , Gao Rui , Chen Jiuhui , Lu Zhanwu , Li Wenhui , Wang Guangwen , Chen Hao , Han Rubing , Niu Xiao , Wu Guowei , Chen Si , Cai Yuguo
Published: June 2023

The eastern segment of the Qilian orogenic belt, comprising the Linxia block and Longzhong block, is at the Qinghai–Tibet Plateau’s northeastern margin. The area has experienced multiple tectonic events, including closure of the Qilian Ocean, convergence of the North China block and Qilian terrane, and collision of the Indian and Eurasian plates, forming a complex tectonic framework. To investigate the area’s geological evolution and the suture’s current location between the blocks, we used 3-year data recorded by 33 portable ChinArray II broadband stations (2013–2016). Using three teleseismic P-wave receiver function methods, H-κ stacking and common conversion point stacking (CCP), crustal structure, Poisson’s ratio, and Moho morphology were obtained at 33 stations. The results are described as follows: 1) The Maxianshan fault is an important boundary fault that divides the Linxia block and Longzhong block. The Linxia block’s layered crustal structure is obvious, and there is a low-velocity anomaly in the middle and lower crust, which may contain saline fluid and has Japanese-type island arc characteristics. 2) The layered structure of the Longzhong block’s upper crust is significant, while the middle and lower crust’s layered structure is weak with weak low-velocity characteristics and oceanic-island basaltic crust characteristics. The Longzhong block may have originally been formed by Mariana-type island arcs. 3) The Conrad interface and Moho lateral variation in the Ordos block’s southwestern margin are weak, showing stable craton characteristics. 4) Our results show that the Maxianshan fault cuts through the Earth’s crust and is a continuous west-dipping negative seismic phase in the Common Conversion Point section. The fault zone is the suture line between the Linxia block and Longzhong block. 5) The middle and upper crust of the Liupanshan tectonic belt is thrust upwards on the Ordos block’s southwestern margin, providing deep structural evidence of the Cenozoic uplift of the Liupanshan structural belt.
The diagnosis of scientific reasoning skills: how teachers’ professional knowledge predicts their diagnostic accuracy
Authors: Pickal Amadeus J. , Engelmann Katharina , Chinn Clark A. , Neuhaus Birgit J. , Girwidz Raimund , Wecker Christof
Published: June 2023

Diagnostic competences of teachers are an essential prerequisite for the individual support of students and, therefore, highly important. There is a substantial amount of research on teachers’ diagnostic competences, mostly operationalized as diagnostic accuracy, and on how diagnostic competences may be influenced by teachers’ professional knowledge base. While this line of research already includes studies on the influence of teachers’ content knowledge (CK), pedagogical content knowledge (PCK), and pedagogical-psychological knowledge (PK) on the diagnosis of subject-specific knowledge or skills, research on the diagnosis of cross-domain skills (i.e., skills relevant for more than one subject), such as scientific reasoning, is lacking although students’ scientific reasoning skills are regarded as important for multiple school subjects (e.g., biology or physics). This study investigates how the accuracy of pre-service teachers’ diagnosis of scientific reasoning is influenced by teachers’ own scientific reasoning skills (one kind of CK), their topic-specific knowledge (i.e., knowledge about a topic that constitutes the thematic background for teaching scientific reasoning; which is another kind of CK), and their knowledge about the diagnosis of scientific reasoning (one kind of PCK) and whether the relationships between professional knowledge and diagnostic accuracy are similar across subjects. The design of the study was correlational. The participants completed several tests for the kinds of professional knowledge mentioned and questionnaires for several control variables. To ensure sufficient variation in pre-service teachers’ PCK, half of the participants additionally read a text about the diagnosis of scientific reasoning. Afterwards, the participants completed one of two parallel video-based simulations (depicting a biology or physics lesson) measuring diagnostic accuracy. The pre-service teachers’ own scientific reasoning skills (CK) were a statistically significant predictor of diagnostic accuracy, whereas topic-specific knowledge (CK) or knowledge about the diagnosis of scientific reasoning (PCK), as manipulated by the text, were not. Additionally, no statistically significant interactions between subject (biology or physics) and the different kinds of professional knowledge were found. These findings emphasize that not all facets of professional knowledge seem to be equally important for the diagnosis of scientific reasoning skills, but more research is needed to clarify the generality of these findings.
Digital tools in secondary chemistry education – added value or modern gimmicks?
Authors: Wohlfart Olivia , Wagner Alina L. , Wagner Ingo
Published: June 2023

The article addresses the challenges faced by teachers incorporating digital tools into chemistry education to prepare students for responsible participation in a digital society. Against the background of the Technology Acceptance Model (TAM), the study analyzes the value that chemistry teachers place on digital tools and examines specific factors that influence their implementation in teaching. For this purpose, we conducted and analyzed interviews with 10 secondary school chemistry teachers in Germany. The findings revealed that while subject-specific digital tools were highly valued by teachers, several barriers to their strategic integration exist, including time constraints, high workloads, failing infrastructure, lack of technical support, and a fear of change. The study concludes that subject-specific digital tools have the potential to enhance learning outcomes and recommends teacher training and further education as well as future research to focus on developing and supporting opportunities for teachers to implement subject-specific digital tools to create a more dynamic and engaging learning experiences for students.
Sarcopenic obesity: epidemiology, pathophysiology, cardiovascular disease, mortality, and management
Authors: Wei Shibo , Nguyen Thanh T. , Zhang Yan , Ryu Dongryeol , Gariani Karim
Published: June 2023

Sarcopenic obesity is defined as the coexistence of sarcopenia and obesity in the same individual, characterized by of the co-presence of body fat accumulation and muscle loss. This condition is currently a major concern as it is associated with frailty and disabilities such as cardiovascular disease, fractures, dementia, cancer, and increased all-cause mortality. Particularly, older individuals remain at risk of sarcopenic obesity. Progress at several levels is needed to improve the global prognostic outlook for this condition, including the elaboration and implementation of a more uniform definition that may favor the identification and specification of prevalence by age group. Furthermore, improvements in the understanding of the pathogenesis of sarcopenic obesity may lead to the development of more specific therapeutic interventions to improve prognosis. We reviewed the knowledge on sarcopenic obesity and its associations with cardiovascular diseases and mortality.
Correlation between visual scores and parathyroid function
Authors: Lorente-Poch Leyre , de Miguel-Palacio Maite , Sancho-Insenser Joan
Published: June 2023

This mini review summarizes the controversies regarding routine parathyroid identification reviews publications that assess visual scores to predict parathyroid function after thyroidectomy during the pre-ICG era.
Modelling and optimization of phase change materials (PCM)-based passive cooling of solar PV panels in multi climate conditions
Authors: Durez Asif , Ali Muzaffar , Waqas Adeel , Nazir Kamran , Kumarasamy Sudhakar
Published: June 2023

To address the increasing energy demand, replacing conventional energy systems with non-conventional resources like solar power generation is crucial. Photovoltaic (PV) panels play a significant role in harnessing solar energy and converting it into electrical power. However, the solar cells’ temperature dramatically influences the panel’s performance, particularly in hot climates. In this study, a detailed mathematical model is developed and conducted simulations using three different phase change materials (PCMs)—RT21, RT35, and RT44—integrated with PV panels in various climate conditions worldwide during the summer season. An optimization model is also created using MATLAB and a genetic algorithm to identify the most suitable PCM for specific climate zones. The findings revealed that incorporating PCM resulted in a surface temperature reduction of PV panels, leading to a 6% increase in efficiency and a 16% boost in electrical output. Specifically, when using a PCM with a melting point of 21°C, the maximum cell temperature during summer operation decreased from 65°C to 38°C. Similar temperature reductions were observed when using PCMs with melting points of 35°C and 44°C. Current analysis demonstrates that the correct selection of a phase change material can decrease panel temperature by approximately 39% in June. Furthermore, PCM with a melting point of 21°C exhibited the best outcomes in terms of maximum electrical performance, efficiency, and PV cell temperature reduction.
A study on livelihood capital, social adaptation, and life satisfaction—empirical analysis based on ecological migration in the Kalajun world natural heritage site
Authors: Hu Jiran , Yao Juan , Xiong Changjiang
Published: June 2023

Improving the life satisfaction of ecological migrants is important for promoting the construction of an ecological civilisation. Based on using sustainable livelihood theory and social adaptation theory to construct an analytical framework for life satisfaction, we innovatively include livelihood capital, social adaptation, and life satisfaction in the same research framework. Using microscopic research data on Kazakh herders in Kalajun, Xinjiang, we empirically analyse the effects of livelihood capital and social adaptation on herders’ life satisfaction using structural equation modelling and further discuss the direct and indirect effects of livelihood capital on life satisfaction. The results show that, first, the mean value of livelihood capital of the sample herding households is below the medium level overall, the mean value of social adaptation is above the medium level, and the life satisfaction of herders is above the medium level. Thus, the ecological migration policy has enhanced the herders’ life satisfaction to a certain extent. Second, financial and natural capital contribute more to the level of livelihood capital, while cultural, life, and psychological adaptation contribute more to the level of social adaptation. Third, both livelihood capital and social adaptation have a significant positive effect on pastoralists’ life satisfaction, i.e., the higher the level of livelihood capital and social adaptation of pastoralists, the more prominent their livelihood capacity and social relations are, and the higher their life satisfaction will be. Fourth, the direct effect of social adaptation on life satisfaction is significantly greater than that of livelihood capital; this should be used to alleviate psychological stress by enhancing herders’ social adaptation abilities. Fifth, the direct impact of livelihood capital on life satisfaction is greater than its indirect impact, and the improvement in human and financial capital will help herders overcome their current livelihood difficulties. The findings of this study will help the government understand the level of livelihood capital and social adaptation of ecological migrant households and provide a reference for further improving ecological migrants’ wellbeing and promoting sustainable regional development.
Influence of alpine meadow deterioration on soil microbial communities in the Yangtze River source region
Authors: Zhang Wenjuan
Published: June 2023

Introduction: Although soil microbial populations are a good predictor of soil texture, little is known about how they react to alpine meadow deterioration.

Methods: This study utilized Illumina HiSeq sequencing to investigate the effects of alpine meadow degradation on soil microbial communities in the Yangtze River source basin at five different degradation levels [i.e., non–degraded (ND), slightly degraded (LD), moderately degraded (MD), severely degraded (SD), and very severely degraded (VD)].

Results: The results indicated that bacterial and fungal α-diversity were not substantially different (p > 0.05) across the damaged alpine meadows, while β-diversity significantly differed (p < 0.01), indicating a higher variation in the microbial community due to alpine meadow degradation. Proteobacteria reduced considerably (p < 0.05) by 8.75%, 22.99%, and 24.65%, while Acidobacteria increased significantly (p < 0.05) by 41.67%, 85.20%, and 108.67%, in MD, SD, and VD compared with ND, respectively. Ascomycota declined significantly (p < 0.05) in the MD, whereas unclassified phyla rose significantly (p > 0.05) in the VD compared to the ND. The heatmaps of bacterial and fungal communities revealed two clusters: a ND, LD, and MD group and a SD and VD group, suggesting significant changes in soil microorganisms of alpine meadow in the SD and VD. Redundancy analysis (RDA) revealed that soil moisture, soil bulk density, soil organic carbon, total nitrogen, and plant biomass could explain 73.8% and 39.4% of the variance in bacterial and fungal community structure, respectively.

Discussion: These findings imply that degradation of the alpine meadow impacts both plant and soil qualities, ultimately leading to changes in soil microbial populations in the Yangtze River’s source region.
Sero-prevalence and factors associated with anti-Brucella antibodies in slaughter livestock in Uganda
Authors: Bugeza James , Roesel Kristina , Moriyon Ignacio , Mugizi Denis , Alinaitwe Lordrick , Kivali Velma , Kankya Clovice , Cook Elizabeth Anne Jessie
Published: June 2023

Introduction

Brucellosis is endemic in Uganda and is a major cause of production losses in livestock. Early detection and quantification of the disease is vital for its control and eradication. The aim of this study was to assess the sero-prevalence and factors associated with anti-Brucella antibodies in slaughtered livestock.

Materials and methods

Sera from 886 cattle, 925 small ruminants, and 900 pigs were collected from regional abattoirs in Northern, Eastern and Central Uganda. To estimate sero-prevalence, sera were serially tested using a combination of the Rose Bengal Test (RBT) and Native Hapten (NH) immunoprecipitation test. True sero-prevalence was estimated using the Rogan-Gladden estimator considering the sensitivity and specificity of the NH immunoprecipitation test. Multivariable logistic regression was used to assess factors associated with seropositivity for anti-Brucella antibodies.

Results and discussion

Small ruminants showed the highest seroprevalence (6.7%, 95% CI = 4.2-7.1) followed by cattle (3.8%, 95% CI = 2.4-4.9) and pigs (2.8%, 95% CI = 1.1-2.9). Seropositivity for anti-Brucella antibodies was associated with region of origin (OR = 4.6,95%CI=1.49-17.75, p = 0.013) for cattle; sex (OR = 2.90, 95% C = 1.5-6.34, p = 0.004), age (OR=4.04, 95% CI = 1.07-8.52, p = 0.006) and species (OR = 2.53, 95% CI = 1.08-6.98, p = 0.048) for small ruminants; and finally sex for pigs (OR = 2.88, 95% CI = 1.07-8.52, p = 0.041). Progressive control interventions must include both cattle and small ruminants since they play a bigger role in the maintenance and dissemination of Brucella. The interventions should adopt a risk-based approach with regions at higher risk being given top priority. Bacteriological and molecular studies should be undertaken to clarify the role of pigs and the goat-cattle cross infections in the epidemiological cycle of brucellosis in Uganda.
Adapting to the future: examining the impact of transport automation and digitalization on the labor force through the perspectives of stakeholders in all transport sectors
Authors: Polydoropoulou Amalia , Thanopoulou Helen , Karakikes Ioannis , Pronello Cristina , Tyrinopoulos Yannis
Published: June 2023

Automation in transport and digitalization will affect both transport users and its workforce. Focusing on the latter, this paper aims at analyzing barriers, gaps, opportunities, and success and failure factors of transport automation on the labor force, through the perceptions and contributions of employees and employers, as well as of stakeholders from the private, public, and private–public sectors. In a nutshell, the study aims to understand workforce-related barriers and facilitators associated with the implementation of automation. This has been achieved through input derived from the organization of five focus groups, one poll and one extensive questionnaire survey administered to the participants of the 2nd WE-TRANSFORM EU H2020 funded project Workshop, and to project partners’ stakeholder contacts. The analysis of the results indicated that the transport sector’s automation has been evolving at a different pace per sector. An interesting conclusion is that the challenges do not concern all categories among the workforce in the same way. Challenges related to loss of jobs and related repercussions are bound to affect groups within the workforce, which may be constrained by regulatory age limits, or vulnerable, if in part-time employment without access to retraining, which may be the case of workforce members near retirement age or of women limited due to family obligations to part-time employment. The study’s limitations are related to the size of the sample and how representative it is of all stakeholders in the transport sector, including policymakers, regulators, and unions. Future directions should focus on exploring the long-term impacts of automation on the labor force and identify strategies to mitigate the negative effects on vulnerable groups.
PARP2 downregulation in T cells ameliorates lipopolysaccharide-induced inflammation of the large intestine
Authors: Bencsics Máté , Bányai Bálint , Ke Haoran , Csépányi-Kömi Roland , Sasvári Péter , Dantzer Françoise , Hanini Najat , Benkő Rita , Horváth Eszter M.
Published: June 2023

Introduction

T cell-dependent inflammatory response with the upregulation of helper 17 T cells (Th17) and the downregulation of regulatory T cells (Treg) accompanied by the increased production of tumor necrosis alpha (TNFa) is characteristic of inflammatory bowel diseases (IBD). Modulation of T cell response may alleviate the inflammation thus reduce intestinal damage. Poly(ADP-ribose) polymerase-2 (PARP2) plays role in the development, differentiation and reactivity of T cell subpopulations. Our aim was to investigate the potential beneficial effect of T cell-specific PARP2 downregulation in the lipopolysaccharide (LPS) induced inflammatory response of the cecum and the colon.

Methods

Low-dose LPS was injected intraperitoneally to induce local inflammatory response, characterized by increased TNFa production, in control (CD4Cre; PARP2+/+) and T cell-specific conditional PARP2 knockout (CD4Cre; PARP2f/f) mice. TNFa, IL-1b, IL-17 levels were measured by ELISA, oxidative–nitrative stress was estimated by immunohistochemistry, while PARP1 activity, p38 MAPK and ERK phosphorylation, and NF-kB expression in large intestine tissue samples were examined by Western-blot. Systemic & local T cell subpopulation; Th17 and Treg alterations were also investigated using flowcytometry and immunohistochemistry.

Results

In control animals, LPS induced intestinal inflammation with increased TNFa production, while no significant elevation of TNFa production was observed in T cell-specific PARP2 knockout animals. The absence of LPS-induced elevation in TNFa levels was accompanied by the absence of IL-1b elevation and the suppression of IL-17 production, showing markedly reduced inflammatory response. The increase in oxidative-nitrative stress and PARP1-activation was also absent in these tissues together with altered ERK and NF-kB activation. An increase in the number of the anti-inflammatory Treg cells in the intestinal mucosa was observed in these animals, together with the reduction of Treg count in the peripheral circulation.

Discussion

Our results confirmed that T cell-specific PARP2 downregulation ameliorated LPS-induced colitis. The dampened TNFa production, decreased IL-17 production and the increased intestinal regulatory T cell number after LPS treatment may be also beneficial during inflammatory processes seen in IBD. By reducing oxidative-nitrative stress and PARP1 activation, T cell-specific PARP2 downregulation may also alleviate intestinal tissue damage.
A brief history of galectin evolution
Authors: Günther Juliane , Galuska Sebastian Peter
Published: June 2023

Galectins are a family of carbohydrate-binding proteins found in vertebrates in great abundance and diversity in terms of both structure and ligand-binding properties as well as physiological function. Proteins with clear relationships to vertebrate galectins are already found in primitive Bilateria. The increasing amount of accessible well-annotated bilaterian genomes has allowed us to reveal, through synteny analyses, a new hypothesis about the phylogenetic history of the galectin family in this animal group. Thus, we can trace the genomic localization of the putative ancestral Bilateria galectin back to the scallops as a still very primitive slow-evolving bilaterian lineage. Intriguingly, our analyses show that the primordial galectin of the Deuterostomata most likely exhibited galectin-8-like characteristics. This basal standing galectin is characterized by a tandem-repeat type with two carbohydrate recognition domains as well as by a sialic acid binding property of the N-terminal domain, which is typical for galectin-8. With the help of synteny, the amplification of this potential primordial galectin to the broad galectin cosmos of modern jawed vertebrates can be reconstructed. Therefore, it is possible to distinguish between the paralogs resulting from small-scale duplication and the ohnologues generated by whole-genome duplication. Our findings support a substantially new hypothesis about the origin of the various members of the galectin family in vertebrates. This allows us to reveal new theories on the kinship relationships of the galectins of Gnatostomata. In addition, we focus for the first time on the galectines of the Cyclostomata, which as a sister group of jawed vertebrates providing important insights into the evolutionary history of the entire subphylum. Our studies also highlight a previously neglected member of the galectin family, galectin-related protein 2. This protein appears to be a widespread ohnologue of the original tandem-repeat ancestor within Gnathostomata that has not been the focus of galectin research due to its nonclassical galactose binding sequence motif and the fact that it was lost during mammalian evolution.
Analysis of a series of Italian APECED patients with autoimmune hepatitis and gastro-enteropathies
Authors: Paldino Giorgia , Faienza Maria Felicia , Cappa Marco , Pietrobattista Andrea , Capalbo Donatella , Valenzise Mariella , Lampasona Vito , Cudini Annamaria , Carbone Elena , Pagliarosi Olivia , Maggiore Giuseppe , Salerno Mariacarolina , Betterle Corrado , Fierabracci Alessandra
Published: June 2023

Introduction

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome is a rare monogenic disease determined by biallelic mutations in AIRE gene, which encodes a transcription factor essential for central immune tolerance. Classic diagnosis is determined by the presence of two of the main APECED clinical diseases: chronic mucocutaneous candidiasis, chronic hypoparathyroidism, and Addison’s disease. Non-endocrine autoimmunity, involving the liver, intestine, eyes, and kidneys, is generally reported in a minority of European patients, while American APECED patients have a higher tendency of developing organ-specific non-endocrine manifestations early in life. This observation led to the revision of the diagnostic criteria to permit earlier diagnosis based on the appearance of one classic triad symptom or one non-classical manifestation at a young age in the presence of IFNωAbs or AIRE mutations (Ferre-Lionakis criteria).

Patients and methods

We analyzed the clinical, genetic, and autoantibody (Ab) profiles in a series of 14 pediatric Italian APECED patients with gastrointestinal manifestations (seven male and seven female patients). Ten patients presented hepatitis (APECED-associated hepatitis (APAH)), while seven were affected by constipation, diarrhea, and malabsorption. Four patients had developed APAH before classic triad symptoms.

Results

Based on the age of appearance of non-endocrine manifestations including APAH and gastro-enteropathy, the Ferre-Lionakis criteria would have allowed an expedited diagnosis in 11/14 patients. Abs to tryptophan hydroxylase (TPHAb) and hepatic aromatic l-amino acid decarboxylase (AADC) were significantly associated with APECED patients of the present series. Abs to cP4501A2 were detectable in the serum of 4/8 patients with APAH, and Abs to cP4502A6 were detectable in 3/8 patients. AADC Abs tested positive in 5/7 patients, which is indicative of gastrointestinal dysfunction in APECED and TPHAb in 5/7 patients with gastrointestinal dysfunction. IFNAb was significantly associated with the syndrome.

Conclusion

Although Ferre-Lionakis expanded criteria applied to the American cohorts of APECED patients would require validation in independent large cohorts of European patients, the results of this study emphasize the importance to evaluate the presence and the age of appearance of APAH and autoimmune enteropathy even in European cohorts for an earlier APECED diagnosis. An earlier APECED diagnosis would also allow the prevention of episodes of life-threatening hypocalcemic seizures and adrenal crisis, which are the main manifestations of undiagnosed APECED.
Altered profile of glycosylated proteins in serum samples obtained from patients with Hashimoto′s thyroiditis following depletion of highly abundant proteins
Authors: Xu Yaozheng , Huo Jiawen , Nie Ruili , Ge Lili , Xie Chonghong , Meng Yuan , Liu Jianhua , Wu Lina , Qin Xiaosong
Published: June 2023

Objectives

Hashimoto’s thyroiditis (HT) is one of the most common autoimmune disorders; however, its underlying pathological mechanisms remain unclear. Although aberrant glycosylation has been implicated in the N-glycome of immunoglobulin G (IgG), changes in serum proteins have not been comprehensively characterized. This study aimed to investigate glycosylation profiles in serum samples depleted of highly abundant proteins from patients with HT and propose the potential functions of glycoproteins for further studies on the pathological mechanisms of HT.

Methods

A lectin microarray containing 70 lectins was used to detect and analyze glycosylation of serum proteins using serum samples (N=27 HT; N=26 healthy control [HC]) depleted of abundant proteins. Significant differences in glycosylation status between HT patients and the HC group were verified using lectin blot analysis. A lectin-based pull-down assay combined with mass spectrometry was used to investigate potential glycoproteins combined with differentially present lectins, and an enzyme-linked immunosorbent assay (ELISA) was used to identify the expression of targeted glycoproteins in 131 patients with papillary thyroid carcinoma (PTC), 131 patients with benign thyroid nodules (BTN) patients, 130 patients with HT, and 128 HCs.

Results

Compared with the HC group, the majority of the lectin binding signals in HT group were weakened, while the Vicia villosa agglutinin (VVA) binding signal was increased. The difference in VVA binding signals verified by lectin blotting was consistent with the results of the lectin microarray. A total of 113 potential VVA-binding glycoproteins were identified by mass spectrometry and classified by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses. Using ELISA, we confirmed that lactoferrin (LTF) and mannan-binding lectin-associated serine protease 1 (MASP-1) levels were elevated in the serum of patients with HT and PTC.

Conclusion

Following depletion of abundant proteins, remaining serum proteins in HT patients exhibited lower glycosylation levels than those observed in HCs. An increased level of potential VVA-binding glycoproteins may play an important role in HT development. LTF and MASP-1 expression was significantly higher in the serum of HT and PTC patients, providing novel insight into HT and PTC.
The role of the gut microbiota in gastric cancer: the immunoregulation and immunotherapy
Authors: Wang Meiqi , Yang Ge , Tian Yuan , Zhang Qihe , Liu Zhuo , Xin Ying
Published: June 2023

Gastric cancer (GC) is one of the most common cancers, leading to the deaths of millions of people worldwide. Therefore, early detection and effective therapeutic strategies are of great value for decreasing the occurrence of advanced GC. The human microbiota is involved not only in the maintenance of physiological conditions, but also in human diseases such as obesity, diabetes, allergic and atopic diseases, and cancer. Currently, the composition of the bacteria in the host, their functions, and their influence on disease progression and treatment are being discussed. Previous studies on the gut microbiome have mostly focused on Helicobacter pylori (Hp) owing to its significant role in the development of GC. Nevertheless, the enrichment and diversity of other bacteria that can modulate the tumor microenvironment are involved in the progression of GC and the efficacy of immunotherapy. This review provides systematic insight into the components of the gut microbiota and their application in GC, including the specific bacteria of GC, their immunoregulatory effect, and their diagnostic value. Furthermore, we discuss the relationship between the metabolism of microbes and their potential applications, which may serve as a new approach for the diagnosis and treatment of GC.
Immunogenic landscape and risk score prediction based on unfolded protein response (UPR)-related molecular subtypes in hepatocellular carcinoma
Authors: Guo Hanyao , Zhang Sidi , Zhang Bo , Shang Yanan , Liu Xiaoyu , Wang Meixia , Wang Hongyu , Fan Yumei , Tan Ke
Published: June 2023

Background

Hepatocellular carcinoma (HCC) is the most common type of cancer and causes a significant number of cancer-related deaths worldwide. The molecular mechanisms underlying the development of HCC are complex, and the heterogeneity of HCC has led to a lack of effective prognostic indicators and drug targets for clinical treatment of HCC. Previous studies have indicated that the unfolded protein response (UPR), a fundamental pathway for maintaining endoplasmic reticulum homeostasis, is involved in the formation of malignant characteristics such as tumor cell invasiveness and treatment resistance. The aims of our study are to identify new prognostic indicators and provide drug treatment targets for HCC in clinical treatment based on UPR-related genes (URGs).

Methods

Gene expression profiles and clinical information were downloaded from the TCGA, ICGC and GEO databases. Consensus cluster analysis was performed to classify the molecular subtypes of URGs in HCC patients. Univariate Cox regression and machine learning LASSO algorithm were used to establish a risk prognosis model. Kaplan–Meier and ROC analyses were used to evaluate the clinical prognosis of URGs. TIMER and XCell algorithms were applied to analyze the relationships between URGs and immune cell infiltration. Real time-PCR was performed to analyze the effect of sorafenib on the expression levels of four URGs.

Results

Most URGs were upregulated in HCC samples. According to the expression pattern of URGs, HCC patients were divided into two independent clusters. Cluster 1 had a higher expression level, worse prognosis, and higher expression of immunosuppressive factors than cluster 2. Patients in cluster 1 were more prone to immune escape during immunotherapy, and were more sensitive to chemotherapeutic drugs. Four key UPR genes (ATF4, GOSR2, PDIA6 and SRPRB) were established in the prognostic model and HCC patients with high risk score had a worse clinical prognosis. Additionally, patients with high expression of four URGs are more sensitive to sorafenib. Moreover, ATF4 was upregulated, while GOSR2, PDIA6 and SRPRB were downregulated in sorafenib-treated HCC cells.

Conclusion

The UPR-related prognostic signature containing four URGs exhibits high potential application value and performs well in the evaluation of effects of chemotherapy/immunotherapy and clinical prognosis.
Liver immunopathogenesis in fatal cases of dengue in children: detection of viral antigen, cytokine profile and inflammatory mediators
Authors: Moragas Leandro Junqueira , Alves Felipe de Andrade Vieira , Oliveira Lucca de Lima Siqueira , Salomão Natália Gedeão , Azevedo Caio Gonçalves , da Silva Jemima Fuentes Ribeiro , Basílio-de-Oliveira Carlos Alberto , Basílio-de-Oliveira Rodrigo , Mohana-Borges Ronaldo , de Carvalho Jorge José , Rosman Fernando Colonna , Paes Marciano Viana , Rabelo Kíssila
Published: June 2023

Introduction

Dengue virus (DENV), the etiologic agent of dengue fever illness, represents a global public health concern, mainly in tropical and subtropical areas across the globe. It is well known that this acute viral disease can progress to severe hemorrhagic stages in some individuals, however, the immunopathogenic basis of the development of more severe forms by these patients is yet to be fully understood.

Objective

In this context, we investigated and characterized the histopathological features as well as the cytokine profile and cell subpopulations present in liver tissues from three fatal cases of DENV in children.

Methods

Hematoxylin and Eosin, Periodic Acid Schiff and Picro Sirius Red staining were utilized for the histopathological analysis. Immunohistochemistry assay was performed to characterize the inflammatory response and cell expression patterns.

Results

Vascular dysfunctions such as hemorrhage, vascular congestion and edema associated with a mononuclear infiltrate were observedin all three cases. Liver tissues exhibited increased presence of CD68+ and TCD8+ cells as well as high expression of MMP-9, TNF-a, RANTES, VEGFR-2 mediators. Viral replication was confirmed by the detection of NS3 protein.

Conclusion

Taken together, these results evidenced key factors that may be involved in the development of severe alterations in liver tissues of children in response to DENV infection.
Creatively connecting science, society and the sea: a mini-review of academic literature focusing on art-science collaborations and the ocean
Authors: Whittaker Geraint Rhys
Published: June 2023

Collaborations between artists and ocean scientists are becoming increasingly frequent. As the UN Ocean Decade (2021-2030) stresses the importance of engaging with the public, there is a growing interest in using art as a tool for communication as well as for scientific exploration and experimentation. This mini-review charts the current academic research on art-science collaborations and the ocean, focusing on literature where artists and scientists work together to produce something based on scientific research. The study finds that these relationships are never apolitical, are complex and develop differently depending on each project. In sum the paper will highlight that although the academic literature is limited, its diversity has the potential to reach numerous academic disciplines and that focusing on process and engagement should be a direction for further research to help broaden the academic reach of these important oceanic knowledges.
Fatigue presentation, severity, and related outcomes in a prospective cohort following post-COVID-19 hospitalization in British Columbia, Canada
Authors: Magel Tianna , Meagher Emily , Boulter Travis , Albert Arianne , Tsai Melody , Muñoz Carola , Carlsten Chris , Johnston James , Wong Alyson W. , Shah Aditi , Ryerson Chris , Mckay Rhonda Jane , Nacul Luis
Published: June 2023

Introduction

Increasing evidence on long-term health outcomes following SARS CoV-2 infection shows post-viral symptoms can persist for months. These symptoms are often consistent with those of Myalgic Encephalomyelitis or Chronic Fatigue Syndrome (ME/CFS). The aim of the present study was to examine the prevalence and outcome predictors of post-viral fatigue and related symptoms 3- and 6-months following symptom onset.

Methods

A prospective cohort of patients hospitalized with Coronavirus disease (COVID-19) (n = 88) were recruited from a Post-COVID-19 Respiratory Clinic (PCRC) in Vancouver, Canada to examine predictors of long-term fatigue and substantial fatigue. Multivariable mixed effects analyses examined the relationship between patient predictors, including pre-existing comorbidities, patient reported outcome measures, and fatigue and substantial fatigue at follow-up.

Results

The number of patients experiencing fatigue or substantial fatigue at 3 months post-infection were 58 (67%) and 14 (16%) respectively. At 6 months these numbers declined to 47 (60%) patients experiencing fatigue and 6 (6%) experiencing substantial fatigue. Adjusted analysis, for sex, age, and time, revealed the number of pre-existing comorbidities to be associated with fatigue (OR 2.21; 95% CI 1.09–4.49; 0.028) and substantial fatigue (OR 1.73; 95% CI 1.06–2.95; 0.033) at 3 months follow-up. Except for shortness of breath, self-care, and follow-up time, all follow-up variables were found to be associated with fatigue and substantial fatigue at 3 months.

Conclusion

Fatigue and substantial fatigue are common after COVID-19 infection but often diminish over time. A significant number of patients continue to exhibit long-term fatigue at 6 months follow-up. Further research is needed to clarify the causality of viral infections in the development and severity of fatigue as a symptom and in meeting post-viral fatigue syndrome or ME/CFS diagnostic criteria.