bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-oral manifestations in adults with a clinical and molecularly confirmed diagnosis of periodontal Ehlers-Danlos syndrome
Authors: Angwin C. , Zschocke J. , Kammin T. , Björck E. , Bowen J. , Brady A. F. , Burns H. , Cummings C. , Gardner R. , Ghali N. , Gröbner R. , Harris J. , Higgins M. , Johnson D. , Lepperdinger U. , Milnes D. , Pope F. M. , Sehra R. , Kapferer-Seebacher I. , Sobey G. , Van Dijk F. S. 
Published: May 2023

Introduction: Periodontal Ehlers-Danlos Syndrome (pEDS) is a rare autosomal dominant type of EDS characterised by severe early-onset periodontitis, lack of attached gingiva, pretibial plaques, joint hypermobility and skin hyperextensibility as per the 2017 International EDS Classification. In 2016, deleterious pathogenic heterozygous variants were identified in C1R and C1S, which encode components of the complement system.Materials and Methods: Individuals with a clinical suspicion of pEDS were clinically and molecularly assessed through the National EDS Service in London and Sheffield and in genetic services in Austria, Sweden and Australia. Transmission electron microscopy and fibroblast studies were performed in a small subset of patients.Results: A total of 21 adults from 12 families were clinically and molecularly diagnosed with pEDS, with C1R variants in all families. The age at molecular diagnosis ranged from 21–73 years (mean 45 years), male: female ratio 5:16. Features of easy bruising (90%), pretibial plaques (81%), skin fragility (71%), joint hypermobility (24%) and vocal changes (38%) were identified as well as leukodystrophy in 89% of those imaged.Discussion: This cohort highlights the clinical features of pEDS in adults and contributes several important additional clinical features as well as novel deleterious variants to current knowledge. Hypothetical pathogenic mechanisms which may help to progress understanding and management of pEDS are also discussed.
The same heterozygous Col4A4 mutation triggered different renal pathological changes in Chinese family members
Authors: Zhu Fengming , Li Yueqiang , Wang Yuxi , Yao Ying , Zeng Rui 
Published: May 2023

Background: Mutations in the collagen components of the glomerular basement membrane (GBM) often lead to hereditary glomerulonephritis. Previous studies have identified that autosomal dominant mutations of Col4A3, Col4A4 or Col4A5 are associated with thin basement membrane nephropathy (TBMN), Alport syndrome and other hereditary kidney diseases. However, the genetic mutations underlying other glomerulonephritis types have not been elucidated.Methods: In this study, we investigated a Chinese family with hereditary nephritis using the methods of genetic sequencing and renal biopsy. Genomic DNA was extracted from peripheral blood of the proband and her sister, and subsequently was performed genetic sequencing. They were found to have the similar mutation sites. Other family members were then validated using Sanger sequencing. The proband and her sister underwent renal puncture biopsies, and experienced pathologists performed PAS, Masson, immunofluorescence, and immunoelectron microscopic staining of the kidney tissue sections.Results: Through genetic sequencing analysis, we detected a novel heterozygous frameshift mutation c.1826delC in the COL4A4 (NM_000092.4) gene coding region, and 1 hybrid missense variation c.86G&gt;A (p. R29Q) was also detected in the TNXB (NM_019105.6) gene coding region in several members of this Chinese family. Interestingly, we found that the same mutations caused different clinical features and distinct pathological changes in individual family members, which confirmed that pathological and genetic testing are crucial for the diagnosis and treatment of hereditary kidney diseases.Conclusion: In this study, we found a novel heterozygous mutation in Col4A4 and co-mutations of the TNXB gene in this Chinese family. Our study indicated that the same Col4A4 mutated variants produced different pathological and clinical changes in different family members. This discovery may provide novel insights into the study of hereditary kidney disease. In addition, new genetic biology techniques and renal biopsy of individual family members are essential.
A novel anoikis-related gene prognostic signature and its correlation with the immune microenvironment in colorectal cancer
Authors: Xiao Yu , Zhou Han , Chen Yiran , Liu Libin , Wu Qian , Li Hui , Lin Peicheng , Li Jinluan , Wu Junxin , Tang Lirui 
Published: May 2023

Background: Anoikis is a type of apoptosis associated with cell detachment. Resistance to anoikis is a focal point of tumor metastasis. This study aimed to explore the relationship among anoikis-related genes (ARGs), immune infiltration, and prognosis in colorectal cancer (CRC).Methods: The transcriptome profile and clinical data on patients with CRC were retrieved from The Cancer Genome Atlas and Gene Expression Omnibus databases. Patients were divided into two clusters based on the expression of ARGs. Differences between the two ARG molecular subtypes were analyzed in terms of prognosis, functional enrichment, gene mutation frequency, and immune cell infiltration. An ARG-related prognostic signature for predicting overall survival in patients with CRC was developed and validated using absolute value convergence and selection operator (LASSO) regression analysis. The correlation between the signature risk score and clinicopathological features, immune cell infiltration, immune typing, and immunotherapy response was analyzed. The risk score combined with clinicopathological characteristics was used to construct a nomogram to assess CRC patients’ prognosis.Results: Overall, 151 ARGs were differentially expressed in CRC. Two ARG subtypes, namely, ARG-high and ARG-low groups, were identified and correlated with CRC prognosis. The gene mutation frequency and immune, stromal, and ESTIMATE scores of the ARG-high group were higher than those of the ARG-low group. Moreover, CD8, natural killer cells, M1 macrophages, human leukocyte antigen (HLA), and immune checkpoint-related genes were significantly increased in the ARG-high group. An optimized 25-gene CRC prognostic signature was successfully constructed, and its prognostic predictive ability was validated. The high-risk score was correlated with T, N, M, and TNM stages. Risk scores were negatively correlated with dendritic cells, eosinophils, and CD4 cells, and significantly positively correlated with regulatory T cells. Patients in the high-risk group were more likely to exhibit immune unresponsiveness. Finally, the nomogram model was constructed and showed good prognostic predictive power.Conclusion: ARGs are associated with clinicopathological features and the prognosis of CRC, and play important roles in the immune microenvironment. Herein, we underpinned the usefulness of ARGs in CRC to develop more effective immunotherapy techniques.
In-stent restenosis is associated with proliferative skin healing and specific immune and endothelial cell profiles: results from the RACHEL trial
Authors: Lozano Íñigo , Bangueses Roi , Rodríguez Isabel , Pevida Marta , Rodríguez-Aguilar Raúl , Rodríguez Diana , Espasandín-Arias Martina , Llames Sara , Meana Álvaro , Suárez Ana , Rodríguez-Carrio Javier 
Published: May 2023

IntroductionIn-stent restenosis (ISR) is a major challenge in interventional cardiology. Both ISR and excessive skin healing are aberrant hyperplasic responses, which may be functionally related. However, the cellular component underlying ISR remains unclear, especially regarding vascular homeostasis. Recent evidence suggest that novel immune cell populations may be involved in vascular repair and damage, but their role in ISR has not been explored. The aims of this study is to analyze (i) the association between ISR and skin healing outcomes, and (ii) the alterations in vascular homeostasis mediators in ISR in univariate and integrative analyses.Methods30 patients with ≥1 previous stent implantation with restenosis and 30 patients with ≥1 stent without restenosis both confirmed in a second angiogram were recruited. Cellular mediators were quantified in peripheral blood by flow cytometry. Skin healing outcomes were analyzed after two consecutive biopsies.ResultsHypertrophic skin healing was more frequent in ISR patients (36.7%) compared to those ISR-free (16.7%). Patients with ISR were more likely to develop hypertrophic skin healing patterns (OR 4.334 [95% CI 1.044–18.073], p=0.033), even after correcting for confounders. ISR was associated with decreased circulating angiogenic T-cells (p=0.005) and endothelial progenitor cells (p&lt;0.001), whereas CD4+CD28null and detached endothelial cells counts were higher (p&lt;0.0001 and p=0.006, respectively) compared to their ISR-free counterparts. No differences in the frequency of monocyte subsets were found, although Angiotensin-Converting Enzyme expression was increased (non-classical: p&lt;0.001; and intermediate: p&lt;0.0001) in ISR. Despite no differences were noted in Low-Density Granulocytes, a relative increase in the CD16- compartment was observed in ISR (p=0.004). An unsupervised cluster analysis revealed the presence of three profiles with different clinical severity, unrelated to stent types or traditional risk factors.ConclusionISR is linked to excessive skin healing and profound alterations in cellular populations related to vascular repair and endothelial damage. Distinct cellular profiles can be distinguished within ISR, suggesting that different alterations may uncover different ISR clinical phenotypes.
Development of innate immune memory by non-immune cells during Staphylococcus aureus infection depends on reactive oxygen species
Authors: Chaumond Emmanuel , Peron Sandrine , Daniel Nathalie , Le Gouar Yann , Guédon Éric , Williams David L. , Le Loir Yves , Jan Gwénaël , Berkova Nadia 
Published: May 2023

IntroductionThe mechanisms underlying innate immune memory (trained immunity) comprise epigenetic reprogramming of transcriptional pathways associated with alterations of intracellular metabolism. While the mechanisms of innate immune memory carried out by immune cells are well characterized, such processes in non-immune cells, are poorly understood. The opportunistic pathogen, Staphylococcus aureus, is responsible for a multitude of human diseases, including pneumonia, endocarditis and osteomyelitis, as well as animal infections, including chronic cattle mastitis that are extremely difficult to treat. An induction of innate immune memory may be considered as a therapeutic alternative to fight S. aureus infection.MethodsIn the current work, we demonstrated the development of innate immune memory in non-immune cells during S. aureus infection employing a combination of techniques including Enzyme-linked immunosorbent assay (ELISA), microscopic analysis, and cytometry. ResultsWe observed that training of human osteoblast-like MG-63 cells and lung epithelial A549 cells with β-glucan increased IL-6 and IL-8 production upon a stimulation with S. aureus, concomitant with histones modifications. IL-6 and IL-8 production was positively correlated with an acetylation of histone 3 at lysine 27 (H3K27), thus suggesting epigenetic reprogramming in these cells. An addition of the ROS scavenger N-Acetylcysteine, NAC, prior to β-glucan pretreatment followed by an exposure to S. aureus, resulted in decreased IL-6 and IL-8 production, thereby supporting the involvement of ROS in the induction of innate immune memory. Exposure of cells to Lactococcus lactis resulted in increased IL-6 and IL-8 production by MG-63 and A549 cells upon a stimulation with S. aureus that was correlated with H3K27 acetylation, suggesting the ability of this beneficial bacterium to induce innate immune memory. DiscussionThis work improves our understanding of innate immune memory in non-immune cells in the context of S. aureus infection. In addition to known inducers, probiotics may represent good candidates for the induction of innate immune memory. Our findings may help the development of alternative therapeutic approaches for the prevention of S. aureus infection.
Interferon beta treatment is a potent and targeted epigenetic modifier in multiple sclerosis
Authors: Xavier Alexandre , Campagna Maria Pia , Maltby Vicki E. , Kilpatrick Trevor , Taylor Bruce V. , Butzkueven Helmut , Ponsonby Anne-Louise , Scott Rodney J. , Jokubaitis Vilija G. , Lea Rodney A. , Lechner-Scott Jeannette 
Published: May 2023

IntroductionMultiple Sclerosis (MS) has a complex pathophysiology that involves genetic and environmental factors. DNA methylation (DNAm) is one epigenetic mechanism that can reversibly modulate gene expression. Cell specific DNAm changes have been associated with MS, and some MS therapies such as dimethyl fumarate can influence DNAm. Interferon Beta (IFNβ), was one of the first disease modifying therapies in multiple sclerosis (MS). However, how IFNβ reduces disease burden in MS is not fully understood and little is known about the precise effect of IFNβ treatment on methylation.MethodsThe objective of this study was to determine the changes in DNAm associated with INFβ use, using methylation arrays and statistical deconvolutions on two separate datasets (total ntreated = 64, nuntreated = 285).ResultsWe show that IFNβ treatment in people with MS modifies the methylation profile of interferon response genes in a strong, targeted, and reproducible manner. Using these identified methylation differences, we constructed a methylation treatment score (MTS) that is an accurate discriminator between untreated and treated patients (Area under the curve = 0.83). This MTS is time-sensitive and in consistent with previously identified IFNβ treatment therapeutic lag. This suggests that methylation changes are required for treatment efficacy. Overrepresentation analysis found that IFNβ treatment recruits the endogenous anti-viral molecular machinery. Finally, statistical deconvolution revealed that dendritic cells and regulatory CD4+ T cells were most affected by IFNβ induced methylation changes.DiscussionIn conclusion, our study shows that IFNβ treatment is a potent and targeted epigenetic modifier in multiple sclerosis.
HIV-1 activates oxidative phosphorylation in infected CD4 T cells in a human tonsil explant model
Authors: Freeman Tracey L. , Zhao Connie , Schrode Nadine , Fortune Trinisia , Shroff Sanjana , Tweel Benjamin , Beaumont Kristin G. , Swartz Talia H. 
Published: May 2023

IntroductionHuman immunodeficiency virus type 1 (HIV-1) causes a chronic, incurable infection leading to immune activation and chronic inflammation in people with HIV-1 (PWH), even with virologic suppression on antiretroviral therapy (ART). The role of lymphoid structures as reservoirs for viral latency and immune activation has been implicated in chronic inflammation mechanisms. Still, the specific transcriptomic changes induced by HIV-1 infection in different cell types within lymphoid tissue remain unexplored.MethodsIn this study, we utilized human tonsil explants from healthy human donors and infected them with HIV-1 ex vivo. We performed single-cell RNA sequencing (scRNA-seq) to analyze the cell types represented in the tissue and to investigate the impact of infection on gene expression profiles and inflammatory signaling pathways.ResultsOur analysis revealed that infected CD4+ T cells exhibited upregulation of genes associated with oxidative phosphorylation. Furthermore, macrophages exposed to the virus but uninfected showed increased expression of genes associated with the NLRP3 inflammasome pathway.DiscussionThese findings provide valuable insights into the specific transcriptomic changes induced by HIV-1 infection in different cell types within lymphoid tissue. The activation of oxidative phosphorylation in infected CD4+ T cells and the proinflammatory response in macrophages may contribute to the chronic inflammation observed in PWH despite ART. Understanding these mechanisms is crucial for developing targeted therapeutic strategies to eradicate HIV-1 infection in PWH.
Case Report: An unclassified T cell lymphoma subtype with co-expression of TCR αβ and γ chains revealed by single cell sequencing
Authors: Song Wei , Wang Gang , Wang Cheng , Liu Lulu , Zhang Liming , Zhang Ruoyu , Zhang Haixi , Shi Keqian 
Published: May 2023

BackgroundT cell lymphomas (TCL) are a group of heterogeneous diseases with over 40 subtypes. In this study, we identified a novel TCL subtype which was featured by a unique T cell receptor (TCR) presentation, α, β and γ chains were co-existing in a single malignant T cell.Case presentationA 45-year-old male patient was diagnosed T cell lymphoma after 2-month of abdominal distension and liver enlargement. Combining histology review, PET-CT scanning and immunophenotyes, the patient was not classified to any existing TCL subtypes. To better understand this unclassified TCL case, we performed single cell RNA sequencing paired with TCR sequencing on the patient’s PBMC and bone marrow samples. To our surprise, we identified that the malignant T cells had a very rare TCR combination, by expressing two α chains, one β chain and one γ chain simultaneously. We further studied the molecular pathogenesis and tumor cell heterogeneity of this rare TCL subtype. A set of potential therapeutic targets were identified from the transcriptome data, such as CCL5, KLRG1 and CD38.ConclusionsWe identified the first TCL case co-expressing α, β and γ chains and dissected its molecular pathogenesis, providing valuable information for precision medicine options for this novel TCL subtype.
Characteristics of submesoscale eddy structures within mesoscale eddies in the Gulf of Mexico from 1/48° ECCO estimates
Authors: Ernst Paul A. , Subrahmanyam Bulusu , Trott Corinne B. , Chaigneau Alexis 
Published: May 2023

Submesoscale oceanic structures (&lt;10-20 km) such as eddies and fronts are often difficult to describe given the influence of the mesoscale. In order to characterize the surface signatures of submesoscale structures, we utilize a custom spatial filtering function to separate the meso- and large-scale sea surface height (SSH) signal from the small scale SSH signal of 1/48° high resolution estimates provided by NASA’s Estimating the Circulation and Climate of the Oceans (ECCO) project. In this study, we use ECCO estimates from a 14-month global simulation between September 2011 and November 2012 with a 2 km horizontal grid spacing in the Gulf of Mexico. We then use an eddy detection and tracking algorithm to identify persistent circular features on both scales, giving rise to an atlas of submesoscale eddy-like variabilities (SEVs). We briefly investigate the geographic and temporal variability of SEVs as a whole before collocating SEVs inside mesoscale eddies, allowing us to evaluate the characteristics of internal SEVs and the impact of SEVs on mesoscale eddies. We find that SEVs, both anticyclonic and cyclonic, are ubiquitous inside mesoscale eddies with lifetimes longer than a week, accounting for an average of 10-20% of the spatial area and eddy kinetic energy of mesoscale eddies. We also show that internal SEVs are persistently associated with temperature and salinity anomalies in both eddy centers and edges of up to 0.1 °C and 0.05 psu, with anticyclonic internal SEVs being warmer and fresher while cyclonic internal SEVs are colder and saltier. Finally, we examine the life cycle of an anticyclonic Loop Current eddy, demonstrating that the number and intensity of internal SEVs within increases as the eddy approaches separation from the Loop Current until a maximum is obtained just after separation. In light of forthcoming submesoscale SSH observations from NASA’s Surface Water and Ocean Topography (SWOT) mission, our results showcase the variability of submesoscale eddy structures and their possible implications for biogeochemical cycling, the inverse energy cascade, and Loop Current prediction techniques.
Feeding on the smallest cells: an in situ study of picoplankton capture by bivalve molluscs from oligotrophic waters
Authors: Amit Tal , Moskovich Raz , Jacobi Yuval , Shumway Sandra E. , Ward J. Evan , Beninger Peter , Yahel Gitai , Loya Yossi 
Published: May 2023

IntroductionBivalve molluscs are among the most prominent coastal benthic-suspension-feeders and their farming is the largest and fastest-growing sector of aquaculture. More than a century of intensive laboratory studies (but surprisingly few in-situ studies) has yielded the consensus view that bivalves mainly capture particles &gt;4µm. Nonetheless, bivalves thrive throughout the world’s oceans that are mostly oligotrophic, characterized by low food concentration and dominated by minute autotrophic picoplankton (&lt;2 µm).MethodWe measured, in situ, the capture efficiency of naturally occurring planktonic cells by five suspension-feeding bivalve species from four families and three orders, residing in two oligotrophic basins: the Red Sea and the East Mediterranean Sea.ResultsThree species captured micron and submicron autotrophic cells with high efficiency (60-90%), suggesting a wider trophic niche than hitherto believed. In contrast, two sympatric species captured mainly particles &gt;10 µm.DiscussionThese results suggest that the same basic anatomical tool kit, variably modulated according to taxa, habitat, or life history traits, enables the remarkable evolutionary and ecological success of bivalves in trophically-diverse habitats.
Surface modification improving the biological activity and osteogenic ability of 3D printing porous dental implants
Authors: Qin Zugan , He Yun , Gao Jingjing , Dong Zhihong , Long Shuai , Cheng Lijia , Shi Zheng 
Published: May 2023

Objective: To explore the mechanical properties, biological activity, and osteogenic ability of 3D printed TC4 titanium (Ti) alloy dental implants treated with surface modification.Methods: Dental implants with 30% porosity were manufactured using selective laser melting (SLM) technology (group 3D), while traditional numerically-controlled machine tools (CNC) were used to manufacture implants without porosity (group SL). The implants were then surface modified through sandblasting and acid etching (groups 3DA1 and SLA1), and then alkali etching (groups 3DA2 and SLA2). The physicochemical properties of the implants were measured using a Vickers hardness instrument, scanning electron microscope (SEM), X-ray diffraction (XRD), energy dispersive spectrometer (EDS), and profilograph before and after surface modification. Next, the biocompatibility, bioactivity, and osteogenic ability of the implants were evaluated using apatite deposition experiments, alkaline phosphatase (ALP) activity, and semiquantitative analysis of extracellular matrix mineralization.Results: There were significant differences in morphology, geometric accuracy, mechanical properties, surface roughness, and hydrophilicity between groups 3D and SL. Furthermore, surface modification improved the physicochemical properties of the porous implants. Implants with sandblasting, acid etching, and alkali etching demonstrated better biocompatibility, bioactivity, and osteogenic ability than implants without surface modification in both groups 3D and SL. Additionally, the implants of groups 3D have higher bioactivity than that of groups SL.Conclusion: Surface modification and the macroporous structure of implants can improve their bioactivity and osteogenic ability, enhancing the application of Ti alloy dental implants.