bluuebunny/crossref_metadata_2025_split huggingface dataset:
Granulomas in common variable immunodeficiency display different histopathological features compared to other granulomatous diseases
Authors: Stigt Astrid C. , Thüsen Jan H. , Mustafa Dana A.M. , Bosch Thierry P.P. , Lila Karishma A. , Vadgama Disha , Hagen Martin van , Dalm Virgil A.S.H. , Dik Willem. A. , IJspeert Hanna 
Published: June 2024

Abstract

Granulomatous disease affects up to 20% of patients with common variable immunodeficiency (CVID). Granulomas are comprised of highly activated immune cells, and emerge in response to antigenic triggers. In CVID granulomas however, the underlying pathophysiology is unclear and the specific trigger remains unknown. Granuloma formation in CVID is often compared to sarcoidosis, although clinical context and prognosis differ, suggesting a different pathogenesis. The aim of this study was to investigate if the cellular organization and proteomics of granulomas in CVID is different from other granulomatous diseases. Therefore, tissue slides from formaldehyde fixed paraffin embedded biopsies obtained from patients with CVID, sarcoidosis, tuberculosis and foreign-material induced pseudo-sarcoidosis were stained with hematoxylin and eosin and assessed for histopathological characteristics. Targeted spatial protein analysis was performed, and immune fluorescent multiplex assays were used to analyze the cellular organization. Histological analysis revealed that CVID granulomas were smaller, less circumscribed, with fewer multinucleated giant cells and minimal fibrosis compared to the other granulomatous diseases. Spatial protein analysis showed that granulomas in all diseases expressed CD68, CD11c, CD44, CD127, and PD-L1. However in CVID, reduced expression of the fibrosis-related protein fibronectin, but enrichment of CD163, CD3 and FAPα inside CVID granulomas was observed. Immunofluorescence analysis conformed a different cellular organization in CVID granulomas with increased influx of neutrophils, macrophages, T and B lymphocytes. In conclusion, granulomas in CVID display a different histological and cellular organization with increased influx of myeloid and lymphoid cells, compared to sarcoidosis, tuberculosis and pseudo-sarcoidosis, indicating a distinct pathogenesis underlying granuloma formation.
Principal component analysis and clustering of proso millet genotypes based on SSR marker diversity
Authors: Santhoshkumar C. , Vaithiyalingan M. , Murugan E. , Renuka R. , Suthamathi P. , Hemalatha G. 
Published: June 2024

Abstract

The current study mainly aims the assessment of the principal component analysis, genetic divergence and molecular diversity studies in proso millet accessions. The conservation and utilization of plant genetic resources require the identification and characterization of germplasm. Molecular markers are commonly utilized to evaluate genetic and taxonomic association, diversity among population structure in various species. In principal component analysis, out of 15 PC components only five components were significant (to assess maximum diversity) and these five components contributed over 78.04% of total phenotypic variance. The PC1 showed positive loading values and maximum variation explaining in the traits plant height, number of basal tillers, flag leaf blade width, flag leaf blade length, peduncle length, panicle length, number of grains per panicle and number of primary inflorescence branches. Seed color shows the highest Shannon-Weaver diversity index (1.306) among all the germplasm accessions followed by leaf pubescence (0.692), growth habit (0.690), inflorescence shape (0.684) and sheath pubescence (0.604). Totally 9 alleles were amplified by 4 polymorphic markers among 24 SSR primers studied. Alleles marked by primers with a range of 2 to 3 alleles and mean of 2.25 alleles per locus. The PIC values of primers ranged from 0.45 (Pm7689) to 0.71 (Pm564). In this study three polymorphic primers exhibited PIC values of more than 0.5. In NTSYS software grouped the 72 proso millet accessions into seven major clusters by using UPGMA clustering method (Table 5). Cluster VI is the largest one which had 19 accessions followed by cluster I (18) and cluster III (18). The similarity coefficient ranges 0.11 to 0.88. lesser similarity coefficient accessions possessed higher genetic variation and hybridization of these accessions may result in desirable recombinants and more advantageous in breeding programs.
Changes in Antibiotic Resistance Before and During the COVID-19 Pandemic: Retrospective Surveillance Study in a Single Indonesian Tertiary Hospital
Authors: Sugianli Adhi Kristianto , Amelia Rachel , Tjoanatan Jerry , Tjandrawati Anna , Turbawaty Dewi Kartika 
Published: June 2024

Abstract

Background: Antibiotic resistance is recognized as a public health threat with significant impacts on mortality and economic burdens. Antibiotic resistance related to inappropriate empiric antibiotics, particularly during the COVID-19 pandemic. However, limited information is available about changes in antibiotic resistance before and during the pandemic in Indonesia. This study aimed to describe changes in the prevalence of antibiotic resistance among patients with proven bacterial infections before and during the COVID-19 pandemic.
Methods: A retrospective surveillance study was carried out at a single tertiary hospital to review medical records containing culture and antibiotic susceptibility data among hospitalized patients diagnosed with sepsis and COVID-19 according to the International Classification of Disease (ICD). In this context, the predefined periods were 1 January–31December 2019 and 1 March 2020–31 December 2021. The result was the percentage of resistance to selected antibiotics among the study population, stratified by gram-bacteria type, with the evaluation of changes in antibiotic resistance over time.
Results: During the observation period, 596 adult patients were diagnosed with sepsis (before COVID-19), and 2786 were diagnosed with confirmed COVID-19 (during COVID-19). The rate of culture growth in patients with sepsis was greater than that in patients with COVID-19, with values of 51.6% and 29.2%, respectively. Gram-negative bacterial isolates were predominantly found in all observation periods, accounting for 41.2% - 47.3% of the adult middle-aged group. Changes in antibiotic resistance against GNB were observed during COVID-19 (peak phase, above 20%) compared to the early phase. For gram-positive bacteria, the greatestchanges were found in the late phase, reaching 70%.
Conclusions: This study revealed that changes in antibiotic resistance before and during the COVID-19 pandemicaffected both GNB and GPB. High antibiotic use and age-related immune responses (i.e., immunosenescence) contributed to these rapid changes. Strengthening strategies, including implementing surveillance systems and antimicrobial stewardship programs and enhancing the capacity of healthcare workers, are recommended for combatting antibiotic resistance.
The study of competing endogenous RNAs regulatory network in hepatocellular carcinoma via bioinformatics
Authors: Huang Tong , Zhao Man , Mao Huajie , Bai Mengge , Zhang Jingyuan , Xia Hua , Wang Yu 
Published: June 2024

Abstract

Background
Hepatocellular carcinoma (HCC) is among the most prevalent and lethal cancers globally and individuals diagnosed at advanced stages. The discovery of new diagnostic and prognostic markers in HCC is urgent. Circular RNAs (circRNAs) have emerged as key players in the intricate landscape of gene regulation through the competing endogenous RNA (ceRNA) mechanism. However, the ceRNA mechanism of circRNAs in HCC still remains unclear.
Methods
This study conducted a comprehensive HCC analysis using GEO database expression profiles for circRNAs, miRNAs, and mRNAs. Differentially expressed genes (DEGs) were revealed and visually presented through R-generated volcano plots and heatmaps. The STRING website and Cytoscape facilitated the construction of a protein-protein interaction (PPI) network. Functional enrichment analyses validated signaling pathways, and a circRNA-miRNA-mRNA network was constructed through Cytoscape.
Results
The study identified 86 differentially expressed mRNAs (33 upregulated, 43 downregulated) across GSE168852, GSE169289, and GSE202069 datasets. Volcano plots and Venn diagrams illustrated gene expression changes. Gene ontology (GO) and Kyoto Encylopedia of Genes and Genomes (KEGG) analysis revealed functional insights. A PPI network identified 8 key genes (HMMR, EXO1, TOP2A, CCNB1, NUF2, CCNB2, BUB1, BUB1B) validated by GEPIA and Kaplan-Meier Plotter. The Cytoscape built ceRNA network unveiled regulatory modules involving 4 mRNAs, 9 miRNAs, and 31 circRNAs.
Conclusions
In summary, this study established circRNA-miRNA-mRNA regulatory modules, including 4 mRNAs, 9 miRNAs, and 31 circRNAs. This offers an effective bioinformatics strategy for studying HCC molecular mechanisms and prognosis. This might provide a realm of the molecular with diagnosis and prognosis biomarkers in HCC.
Improving equitable healthcare resource use: Developing a neighbourhood district nurse needs index for staffing allocation
Authors: Filipe Luís , Piroddi Roberta , Baker Wes , Rafferty Joe , Buchan Iain , Barr Ben 
Published: June 2024

Abstract

Background
Allocating health care resources to local areas in proportion to need is an important element of many universal health care systems, aiming to provide equal access for equal need. The UK National Health Service allocates resources to relatively large areas in proportion to need, using needs-weighted capitation formulae. However, within those planning areas, local providers and commissioners also require robust methods for allocating resources to neighbourhoods in proportion to need to ensure equitable access. We therefore developed a local resource allocation formula for NHS district nursing services for a City in the North West of England, demonstrating a novel approach for equitable resource allocation to small areas.
Methods
Using linked data from community health services, primary care, secondary care and social care, we used a zero-inflated Poisson regression to model the number of district nursing services contacts for each individual based on predictors of need, while including the supply of district nurses per head to account for historical supply induced patterns. Individual need was estimated based on the predictions from this model, keeping supply fixed at the average. We then compared the distribution of district nurses between neighbourhoods, based on our formula, to the current service staffing distribution.
Results
Key predictors of need for district nursing services were age, deprivation, chronic diseases such as, cardiovascular disease, chronic liver disease, neurological disease, mental ill health, learning disability living in a nursing home, living alone, and receiving palliative care. Need for district nursing services was highly weighted towards older and more deprived populations. The current distribution of staff was, however, more correlated with age than deprivation. Moving to a needs-based staffing distribution would shift staff from less deprived areas to more deprived areas potentially reducing inequalities.
Conclusion
A neighbourhood-level model for needs for district nursing is a useful tool that can potentially improve the allocation of resources, addressing unmet need and inequalities.
Open Education on Social Entrepreneurship: A comparative study between Mexico and Bolivia to Scale up Complex Thinking
Authors: Alvarez-Icaza Inés , Marco-Tórrez Liz Katherine , Rondón-Jara Evelyn 
Published: June 2024

Abstract

The Open Education movement has tremendous transformative potential in developing countries and marginalized communities. The implementation of the OpenEdR4C platform, a digital educational resource for entrepreneurship education, was an example of this potential. As an open resource for scaling up complex thinking competencies in higher education students and lifelong learners, the platform has been presented to various institutions and organizations in Mexico and Bolivia. The objective of this article is to show the impact of the digital course on social entrepreneurship on the development of complex thinking skills of the workshop participants. The study was conducted using mixed methods, evaluating the perception of the performance levels of the participants and analyzing their opinions on the benefits brought by the platform. The results showed that (a) the level of performance in complex thinking competence improved after the formative experience, (b) the platform can be a convenient resource for training higher education students and lifelong learners, and (c) social entrepreneurship is a valuable topic to be trained with open educational resources. This study is a contribution to the transformative efforts made by developers of digital open educational resources and educators to build different approaches of competence for work training and social entrepreneurship skills development.
Novel Approach to Exploring Protease Activity and Targets in HIV-associated Obstructive Lung Disease using Combined Proteomic-Peptidomic Analysis
Authors: Samorodnitsky Sarah , Kruk Monica , Lock Eric F. , Kunisaki Ken M. , Morris Alison , Leung Janice M. , Weise Danielle , Mehta Subina , Parker Laurie L. , Jagtap Pratik D. , Griffin Timothy J. , Wendt Chris H. 
Published: June 2024

Abstract

Background: Obstructive lung disease (OLD) is increasingly prevalent among persons living with HIV (PLWH). However, the role of proteases in HIV-associated OLD remains unclear.
Methods: We combined proteomics and peptidomics to comprehensively characterize protease activities. We combined mass spectrometry (MS) analysis on bronchoalveolar lavage fluid (BALF) peptides and proteins from PLWH with OLD (n=25) and without OLD (n=26) with a targeted Somascan aptamer-based proteomic approach to quantify individual proteases and assess their correlation with lung function. Endogenous peptidomics mapped peptides to native proteins to identify substrates of protease activity. Using the MEROPS database, we identified candidate proteases linked to peptide generation based on binding site affinities which were assessed via z-scores. We used t-tests to compare average forced expiratory volume in 1 second per predicted value (FEV1pp) between samples with and without detection of each cleaved protein and adjusted for multiple comparisons by controlling the false discovery rate (FDR).
Findings: We identified 101 proteases, of which 95 had functional network associations and 22 correlated with FEV1pp. These included cathepsins, metalloproteinases (MMP), caspases and neutrophil elastase. We discovered 31 proteins subject to proteolytic cleavage that associate with FEV1pp, with the top pathways involved in small ubiquitin-like modifier mediated modification (SUMOylation). Proteases linked to protein cleavage included neutrophil elastase, granzyme, and cathepsin D.
Interpretations: In HIV-associated OLD, a significant number of proteases are up-regulated, many of which are involved in protein degradation. These proteases degrade proteins involved in cell cycle and protein stability, thereby disrupting critical biological functions.
No Causal Association Between Gut Microbiota and Kawasaki Disease: A Two-Sample Mendelian Randomization Study
Authors: Wang Sibao , Luo Gang , Ji Zhixian , Pan Silin 
Published: June 2024

Abstract

Background: Despite previous observational studies linking gut microbiota to Kawasaki disease (KD), these findings remain controversial. This study aimed to explore the association between gut microbiota and KD at a genetic level, using a two-sample Mendelian randomization (MR) analysis.
Methods: A two-sample MR study utilized summary statistics of gut microbiota from the largest genome-wide association study meta-analysis by the MiBioGen consortium. The causal link between gut microbiota and KD was examined using inverse variance weighted, MR Egger, weighted median, simple mode, weighted mode, and MR-PRESSO methods. Reverse MR analysis was conducted on bacteria identified as causally linked to KD in the initial MR study. Cochran’s Q and Rucker’s Q statistics quantified the heterogeneity among instrumental variables.
Results: Inverse variance weighted estimates suggested no genetic causal correlation with KD for the following taxa: genus Bifidobacterium(p = 0.774, OR 95% CI = 0.876 [0.355–2.163]), genus FamilyXIIIAD3011group(p = 0.945, OR 95% CI = 0.979 [0.539–1.780]), genus LachnospiraceaeUCG004(p = 0.987, OR 95%CI = 1.005 [0.542–1.863]), genus RuminococcaceaeNK4A214group (p = 0.453, OR 95%CI = 1.469 [0.538–4.009]), genus RuminococcaceaeUCG002 (p = 0.835, OR 95% CI = 1.092 [0.478–2.494]), genus LachnospiraceaeUCG001 (p = 0.996, OR 95%CI = 0.998 [0.482–2.066]), genus Bacteroides (p = 0.595, OR 95%CI = 0.831 [0.419–1.648]), genus Olsenella (p = 0.414, OR 95%CI = 1.312 [0.684–2.516]), genus Lactococcus (p = 0.870, OR 95%CI = 0.962 [0.600–1.541]), family Rhodospirillaceae (p = 0.995, OR 95%CI = 1.002 [0.550–1.827]), family FamilyXIII (p = 0.894, OR 95%CI = 1.093 [0.298–4.009]), family BacteroidalesS24 (p = 0.604, OR 95%CI = 0.849 [0.456–1.578]), family Ruminococcaceae (p = 0.524, OR 95%CI = 0.692 [0.223–2.148]), and class Bacilli (p = 0.905, OR 95%CI = 0.967 [0.561–1.667]). The reverse MR analysis revealed no significant causal effect of KD on gut microbiota. No significant heterogeneity of instrumental variables or horizontal pleiotropy was observed.
Conclusion: Our bidirectional causal inference analysis revealed no genetic causal relationship between gut microbiota and KD. Confounding factors might have influenced the observed association in observational studies. Further research requires more advanced MR analysis methods, and larger-scale GWAS datasets.
Drivers of summer Arctic sea-ice extent in CMIP6 large ensembles revealed by information flow
Authors: Docquier David , Massonnet François , Ragone Francesco , Sticker Annelies , Fichefet Thierry , Vannitsem Stéphane 
Published: June 2024

Abstract

Arctic sea-ice extent has strongly decreased since the beginning of satellite observations in the late 1970s. While several drivers are known to be implicated, their respective contribution is not fully understood. Here, we apply the Liang-Kleeman information flow method to five different large ensembles from the Coupled Model Intercomparison Project Phase 6 (CMIP6) over the 1970-2060 period to investigate the extent to which fluctuations in winter sea-ice volume, air temperature and ocean heat transport drive changes in subsequent summer Arctic sea-ice extent. This allows us to go beyond classical correlation analyses. Results show that air temperature is the most important controlling factor of summer sea-ice extent at interannual timescale, and that winter sea-ice volume and Atlantic Ocean heat transport play a secondary role. If we replace air temperature by net shortwave and downward longwave radiations, we find that the sum of influences from both radiations is almost similar to the air temperature influence, with the longwave radiation being dominant in driving changes in summer sea-ice extent. Finally, we find that the influence of air temperature is more prominent during periods of large sea-ice reduction and that this temperature influence has overall increased since 1970.
The FlbC transcription factor contributes to the generation of strain heterogeneity in Fumagillin mycotoxin production in Aspergillus fumigatus
Authors: Tanaka Yutaka , Asagiri Ikumi , Komiya Rei , Yamazaki Hiroyuki , Yagi Akiho , Uchida Ryuji , Sasaki Masato 
Published: June 2024

Abstract

Aspergillus fumigatus shows inter-strain heterogeneity in the repertoire of secondary metabolites such as mycotoxin fumagillin but the mechanism by which this heterogeneity arises in those production is still not understood. Here, we investigates the effect of the flbC gene on fumagillin production in A. fumigatus by introducing flbC deletions into laboratory strains, A1151, A1159, and A1280 from different backgrounds and examines the effect of the flbC gene on inter-strain heterogeneity. We found that, although all three laboratory strains were capable of producing fumagillin, there was heterogeneity in the effects of flbC gene deletion on fumagillin production. This heterogeneity may be dependent on differences in the expression levels of the fma gene family involved in fumagillin production and different levels of transcriptional activation by transcription factors FapR and LaeA. The flbC gene expression level peaks at the same time as peak mycelial growth but shows differential expression level, suggesting that the differences among strains in the range of expression levels are dependent on differences in the upstream expression of flbC. Thus, our findings show that the different interactions between flbC and factors regulating the expression of fumagillin gene cluster are the probable cause for heterogeneity in fumagillin production in the organism.
MPI, pinning and core count- performanceanalysis in numerical oceans acoustics
Authors: Melic Alena 
Published: June 2024

Abstract

The large- scale numerical simulation/solution in three dimensions (3D) of partial differential equations requires significant com-putational resources, regardless of the physics domain (e.g. numericaloceans acoustics, electromagnetic fields, computational fluid dynamics. . . ).The utilization of the Message Passing Interface (MPI) offers a distinctadvantage in enabling large- scale simulations/solutions based on thesedifferential equations. This streamlines the approximation process significantly. By employing MPI, scientists and engineers model effortlesslythe complex interactions from physical parameters in various physics domains. This empowers them to make informed decisions in various fields,from e.g. marine engineering to environmental monitoring. This papershows the efficiency result of a specific software application for the numerical solution of a partial differential equation in numerical oceansacoustics in 3D on a high-performance computer (HPC) with the respective number of cores, pin assignment and MPI Version
Restoration of the endemic hermatypic coral Cladocora caespitosa in the Mediterranean Sea: coral gardening based on micro-fragmentation
Authors: Cardinale Pierfrancesco , Danovaro Roberto 
Published: June 2024

Abstract

Cladocora caespitosa is the only reef-building zooxanthellate coral in the Mediterranean Sea. It forms beds of colonies, sporadically aggregating in extensive reef-like structures. The carbonate deposition of C. caespitosa enhances habitat complexity, supports biodiversity, and contributes to carbon sequestration. This species has been increasingly threatened by anthropogenic pressures. Due to its decline, the International Union for the Conservation of Nature (IUCN) included C. caespitosa in the endangered species list. Here we explored the available knowledge on tropical coral reefs to develop a protocol for the ecological restoration of this Mediterranean species. In this preliminary study, we exploited naturally occurring dislodged fragments as donor material and successfully implemented micro-fragmentation and nursery-rearing techniques on this species, designing a protocol for future restoration interventions. We reported that micro-fragmented C. caespitosa has optimal survival and growth rates surpassing those of naturally occurring juvenile colonies. We also showed that C. caespitosa fragments subjected to a strong heatwave, bleached but survived and recovered after the re-establishment of lower temperatures. Bleached individuals of C. caespitosa were able to grow, although to a much lower rates than those in healthy conditions. The coral gardening proposed here is highly successful, and can be operated at large spatial scales.