bluuebunny/crossref_metadata_2025 huggingface dataset:
Research landscape of genetics in dilated cardiomyopathy: insight from a bibliometric analysis
Authors: Chao Tiantian , Ge Yaru , Sun Jinghui , Wang Chenglong
Published: July 2024

Background

Dilated cardiomyopathy (DCM) is a heterogeneous myocardial disorder with diverse genetic or acquired origins. Notable advances have been achieved in discovering and understanding the genetics of DCM. This study aimed to depict the distribution of the main research forces, hotspots, and frontiers in the genetics of DCM, thus shaping future research directions.

Methods

Based on the documents published in the Web of Science Core Collection database from 2013 to 2022, co-authorship of authors, institutions, and countries/regions, co-citation of references, and co-occurrence of keywords were conducted respectively to present the distribution of the leading research forces, research hotspots, and emerging trends in the genetics of DCM.

Results

4,141 documents were included, and the annual publications have steadily increased. Seidman, Christine E, Meder, Benjamin, Sinagra, Gianfranco were the most productive authors, German Centre for Cardiovascular Research was the most productive institution, and the USA, China, and Germany were the most prolific countries. The co-occurrence of keywords has generated 8 clusters, including DCM, lamin a/c, heart failure, sudden cardiac death, hypertrophic cardiomyopathy, cardiac hypertrophy, arrhythmogenic cardiomyopathy, and next-generation sequencing. Frequent keywords with average publication time after 2019 mainly included arrhythmogenic cardiomyopathy, whole-exome sequencing, RBM 20, phenotype, risk stratification, precision medicine, genotype, and machine learning.

Conclusion

The research landscape of genetics in DCM is continuously evolving. Deciphering the genetic profiles by next-generation sequencing and illustrating pathogenic mechanisms of gene variants, establishing innovative treatments for heart failure and improved risk stratification for SCD, uncovering the genetic overlaps between DCM and other inherited cardiomyopathies, as well as identifying genotype-phenotype correlations are the main research hotspots and frontiers in this field.
Single-center real-world data and technical considerations from 100 consecutive patients treated with the Perceval aortic bioprosthesis
Authors: Müller Hannes , Szalkiewicz Philipp , Benedikt Peter , Ratschiller Thomas , Schachner Bruno , Schröckenstein Sophie , Zierer Andreas
Published: July 2024

Objectives

Although the Perceval sutureless aortic valve bioprosthesis presents a feasible alternative to conventional aortic valve prostheses, the extent of its applicability with respect to technical considerations for a real-world patient collective is still under debate.

Methods

One hundred patients received the Perceval prosthesis [males: 59; age: 72.5 (7.3–79) years] between December 2015 and February 2023 [EuroSCORE II: 2.8 (1.7–5.4)] for an aortic valve replacement (AVR), with additional concomitant procedures, for underlying severe aortic valve stenosis [n = 93 (93)], endocarditis [n = 5 (5)], and redo AVR [n = 7 (7)] including a prior surgical AVR [n = 4 (4)] and a failed transcatheter aortic valve implantation [n = 3 (3)]. Surgery was conducted primarily by median sternotomy [n = 71 (71)] and, alternatively, by the upper hemisternotomy approach [n = 29 (29)].

Results

Over a median follow-up time of 36.5 (16.5–53) months, eight patients (8%) underwent postoperative pacemaker implantation, with five (5%) due to high-grade atrioventricular block, while nine patients experienced a stroke (9%). The median values of maximum and mean gradients across all valve sizes were 22 (18–27.5) mmHg and 10 (13–18) mmHg, respectively. Two patients (2%) had moderate and one (1%) had severe paravalvular leakage, with the latter presenting the only case of underlying valve migration and induced redo AVR with valve explantation 2 days following initial surgery. Thirty-day mortality (and overall mortality) was 5% and 26%, respectively.

Conclusion

The implantation of the Perceval bioprosthesis is feasible for a variety of indications, with excellent hemodynamic results and low complication rates in a real-world high-risk patient collective.
Coupling noble gas and alkane gas isotopes to constrain normally pressured shale gas expulsion in SE Sichuan Basin, China
Authors: Li Jiaxin , Wang Yunhai , Fang Dazhi , Wen Zhigang , Wu Chenjun
Published: July 2024

The molecular and isotopic compositions of shale gases exhibit substantial differences under different storage conditions. Gas geochemistry is widely used when evaluating gas accumulation and expulsion in petroleum systems. Gas geochemical characteristics can provide important references for determining the enrichment mechanism of shale gas reservoirs and predicting shale gas production capacity in different regions. In tectonically stable regions with similar reservoir formation and evolution histories, shale gas reservoirs are expected to exhibit favorable storage conditions with only relatively small variations in gas geochemical characteristics. In tectonically active regions, shale gas preservation conditions are expected to be more variable. In this study, we systematically analyzed the stable isotope signatures (δ13C and δD) of alkane gases (CH4, C2H6, and C3H8), along with noble gas compositions and isotopic signatures, of normally pressured Wufeng‒Longmaxi marine shale gas samples comprising a continuous pressure coefficient series from a structurally active region at the transition between an orogenic belt and the southeastern (SE) Sichuan Basin, China. The relationships between noble gas contents, isotopic signatures, and shale gas yields were evaluated, and a mechanism for normally pressured shale gas accumulation and expulsion was presented. The δ13C and δD data suggest that the normally pressured shale gas originated from late-mature thermogenic generation, equivalent to shale gas from other production areas in the inner Sichuan Basin. Gas dryness ratios [C1/(C2 + C3)] exhibit negative relationships with δ13C1 and δ13C2. Normally pressured shale gas yields exhibit a negative correlation with δ13C and a positive correlation with [C1/(C2 + C3)], suggesting differences in shale gas accumulation and expulsion across the studied region related to changes in the pressure coefficient. Noble gas isotope data suggest that the normally pressured Longmaxi shale gas received a substantial contribution of crust-derived He. Coupling noble gas and stable C/H isotope data reveals that the abundance of He and Ar, along with the δ13C signatures of alkane gases, is affected by the abundance of shale gas during the accumulation and expulsion process. The noble gas and stable isotope distribution trends presented herein can be used to evaluate Wufeng‒Longmaxi’s normally pressured shale gas accumulation and expulsion in complex structural areas of the southeastern Sichuan Basin. Better preservation conditions accompanying lower tectonic activity will normally result in higher shale gas production and a lower concentration of noble gases. The above findings show that gas geochemical characteristics could be used as effective evaluation indicators for determining shale gas accumulation mechanisms in tectonically active regions.
Machine learning reveals that sodium concentration and temperature influence alkenone occurrence in Swiss and worldwide freshwater lakes
Authors: Martin Céline , Richter Nora , Lloren Ronald , Amaral-Zettler Linda , Dubois Nathalie
Published: July 2024

Lacustrine alkenones are increasingly reported in freshwater lakes worldwide, which makes them a very promising proxy to reconstruct past continental temperatures. However, a more systematic understanding of ecological preferences of freshwater alkenone-producers at global scale is lacking, which limits our understanding of alkenones as a proxy in lakes. Here we investigated 56 Swiss freshwater lakes and report Group 1 alkenones in 33 of them. In twelve of the lakes containing alkenones, a mixed Group 1/Group 2 alkenone signature was detected. We used a random forest (RF) model to investigate the influence of 15 environmental variables on alkenone occurrence in Swiss lakes and found sodium (Na+) concentration and mean annual air temperature (MAAT) to be the most important variables. We also trained a RF model on a database that included Swiss lakes and all freshwater lakes worldwide, which were previously investigated for alkenone presence. Water depth appeared as the most important variable followed by MAAT and Na+, sulfate and potassium concentrations. This is very similar to results found for freshwater and saline lakes, which suggests that Group 1 and Group 2 alkenone occurrence could be controlled by the same variables in freshwater lakes. For each tested variable, we defined the optimal range(s) for the presence of alkenones in freshwater lakes. The similarity of the results for the Swiss and global models suggests that the environmental parameters controlling the occurrence of freshwater alkenone producers could be homogenous worldwide.
The intersection of promotion policies, research habitus, and capital distribution: a qualitative case study of two higher education contexts in the United Arab Emirates
Authors: Elhakim Ahmed
Published: July 2024

Introduction

Career advancement must be based on merit, according to the universal norm. However, faculty members continue to express their dissatisfaction with the existing promotion policies and practices, highlighting issues like ambiguity, lack of transparency, inconsistent implementation, and the overall fairness of the evaluation process. This study aimed to explore the intersections of promotion policies with the research habitus and the distribution of different forms of capital in two higher education institutes in the United Arab Emirates.

Methods

Data were gathered from a purposively selected sample of faculty members using semi-structured interviews in addition to key policy documents at both institutes.

Results and discussion

Using Bourdieu’s notion of habitus, capital, and field, the study identified key characteristics of the research habitus and how it shapes perceptions towards aspects of competitiveness and collegiality as practiced in the research world. The study also examined potential relationships between research habitus and promotion policies. Finally, the study explored capital distribution in the research field and identified some of the undisclosed aspects of the promotion world, highlighting areas like prior education, affiliations, professional experience, cultural background, ethnicity, and social networks as some of the factors that may play a role in the promotion outcomes. The findings of the study can be used to offer an additional layer of understanding some hidden rules of academic research fields and capital distribution in light of institutional policy development and enactment. Such understanding can be used to make recommendations on how existing challenges can be addressed to improve perceptions of the clarity and fairness of faculty promotion policies and encourage more transparent practices.
Comparison of radiofrequency ablation and surgery for thyroid papillary microcarcinoma: efficacy, safety and life quality
Authors: Kong Xiaoyan , Wang Liangchen , Sun Yuchen , Zhu Di , Yang Caizhe
Published: July 2024

Objective

To compare the efficacy, safety and patients’ quality of life of radiofrequency ablation (RFA) and surgery in the treatment of papillary thyroid microcarcinoma (PTMC).

Methods

MEDLINE, EMBASE, Cochrane, CNKI and other databases were searched for studies on radiofrequency ablation versus traditional surgery for PTMC up to October 2022. RevMan5.4 software was used for Meta-analysis.

Results

10 articles were selected from 392 articles, including 873 cases of radiofrequency ablation and 781 cases of open surgery. After meta-analysis, the incidence of postoperative complications in the radiofrequency ablation group was lower than that in the surgery group, and the difference was statistically significant [OR=0.24, 95%CI (0.14,0.41), P<0.001]. There were no significant differences in lymph node metastasis rate, local recurrence rate, and new tumor rate between the two groups [OR=1.6, 95%CI (0.21, 12.41), P>0.05; OR=0.85, 95%CI (0.05, 13.8), P>0.05; OR=0.12, 95%CI (0.01, 0.98), P>0.05]. The treatment time and hospital stay in the radiofrequency ablation group were shorter than those in the open surgery group [MD=-49.99, 95%CI (-62.02, -37.97), P<0.001; MD=-5.21, 95%CI(-7.19,-3.23),P<0.001], and the cost was significantly lower than that of the traditional surgery group [SMD=-14.97, 95%CI (-19.14, -10.81), P<0.001]. The quality of life of patients in the radiofrequency ablation group was higher than that in the surgery group [MD=-1.61, 95%CI (-2.06, -1.17), P<0.001].

Conclusion

Compared with traditional open surgery, radiofrequency ablation for papillary thyroid microcarcinoma has the advantages of less trauma, fewer complications, faster recovery and higher quality of life. The indications need to be strictly controlled in the treatment.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier (CRD42022374987).
Single-cell analysis of human PBMCs in healthy and type 2 diabetes populations: dysregulated immune networks in type 2 diabetes unveiled through single-cell profiling
Authors: Gu Doeon , Lim Jinyeong , Han Kyung Yeon , Seo In-Ho , Jee Jae Hwan , Cho Soo Jin , Choi Yoon Ho , Choi Sung Chul , Koh Jang Hyun , Lee Jin-Young , Kang Mira , Jung Dong-Hyuk , Park Woong-Yang
Published: July 2024

Abnormalities in glucose metabolism that precede the onset of type 2 diabetes (T2D) activate immune cells, leading to elevated inflammatory factors and chronic inflammation. However, no single-cell RNA sequencing (scRNA-seq) studies have characterized the properties and networks of individual immune cells in T2D. Here, we analyzed peripheral blood mononuclear cells (PBMCs) from non-diabetes and T2D patients by scRNA-seq. We found that CD14 monocytes in T2D patients were in a pro-inflammatory state and intermediate monocytes expressed more MHC class II genes. In T2D patients, cytotoxic CD4 T cells, effector memory CD8 T cells, and γδ T cells have increased cytotoxicity and clonal expansion. B cells were characterized by increased differentiation into intermediate B cells, plasma cells, and isotype class switching with increased expression of soluble antibody genes. These results suggest that monocytes, T cells, and B cells could interact to induce chronic inflammation in T2D patients with pro-inflammatory characteristics.
The relationship between inflammatory bowel disease and sarcopenia-related traits: a bidirectional two-sample mendelian randomization study
Authors: Sun Zhihuang , Liu Guangwei , Xu Jiajia , Zhang Xianyu , Wei Huahua , Wu Guobao , Jiang Jian
Published: July 2024

Objective

Observational studies have revealed a link between inflammatory bowel disease (IBD) and sarcopenia. However, it remains unclear whether this correlation between IBD and sarcopenia is causal.

Methods

The genetic instrumental variables (IVs) associated with IBD and sarcopenia-related traits were derived from publicly available genome-wide association studies. We employed a two-sample bidirectional Mendelian randomization (MR) method. we obtained genetic IVs for five phenotypes from 34,652 cases in IBD, 27,432 cases in ulcerative colitis (UC), 212356 cases in crohn’s disease (CD), 9336415 cases in low hand grip strength (LHGS), and 450243 cases in appendicular lean mass (ALM), respectively. The inverse variance weighting and other MR methods were used to explore the bidirectional causal relationship. Furthermore, we performed heterogeneity test, pleiotropy test, leave-one-out sensitivity test, and multivariate MR to evaluate the robustness of the results.

Results

The forward MR results showed that the UC (OR=0.994, 95% CI: 0.9876–0.9998, P = 0.044) and CD (OR=0.993, 95% CI: 0.988–0.998, P = 0.006) was negatively correlated with ALM. In the reverse MR analysis, we also found that LHGS was negatively correlated with the IBD (OR=0.76, 95% CI: 0.61–0.94, P = 0.012) and CD (OR=0.53, 95% CI: 0.40–0.70, P <0.001). Besides, genetically predicted higher ALM reduced IBD (OR=0.87, 95% CI: 0.79–0.95, P = 0.002), UC (OR=0.84, 95% CI: 0.76–0.93, P = 0.001), and CD (OR=0.87, 95% CI: 0.77–0.99, P = 0.029). However, the results of other MR Analyses were not statistically different.

Conclusions

We found genetically predicted UC and CD are causally associated with reduced ALM, and higher hand grip strength reduced IBD and CD risk, and higher ALM reduced IBDs risk. This MR study provides moderate evidence for a bidirectional causal relationship between IBD and sarcopenia.
Review of technological developments and LCA applications on biobased SAF conversion processes
Authors: Borrill Eleanor , Koh S. C. Lenny , Yuan Ruoyang
Published: July 2024

The aviation industry, driven by evolving societal needs, faces rising demand post-Covid and increasing pressure to align with emission reduction targets, prompting the development of drop-in sustainable aviation fuels (SAF). Their compatibility with existing aircraft and infrastructure will help to implement these fuels with the urgency the global climate crisis requires. This review delves into the benefits and challenges of various feedstocks, addressing complexities in estimating feedstock availability by location. Identified research gaps include enhancing feedstock availability, yield, and diversity, investigating compositions, and implementing sustainable agricultural practices. A summary of ASTM-certified conversion processes and technical specifications is outlined, prompting further research into conversion efficiency, catalyst selectivity, blending limits, aromatic compounds, combustion instability, and numerical modeling. A summary of recent life cycle assessments (LCA) highlighted gaps in cradle-to-cradle assessments, location-specific analyses, temporal considerations, and broader environmental impact categories. Recommendations stress obtaining primary data for enhanced LCA accuracy, conducting more specialized and general LCA studies and combining LCA, techno-economic analysis, fuel requirements, and socio-political assessments in multi-criteria decision analysis. This paper underlines the pressing need for comprehensive research to inform SAF production alternatives in the context of global climate crisis mitigation.
A cross-tissue transcriptome-wide association study identifies new susceptibility genes for frailty
Authors: Lin Daoyi , Wu Shuyan , Li Wangyu , Ye Peng , Pan Xuan , Zheng Ting , Gao Fei
Published: July 2024

Background: Although genome-wide association studies (GWAS) have identified 14 loci associated with frailty index (FI) susceptibility, the underlying causative genes and biological mechanisms remain elusive.

Methods: A cross-tissue transcriptome-wide association study (TWAS) was conducted utilizing the Unified Test for Molecular Markers (UTMOST), which integrates GWAS summary statistics from 164,610 individuals of European ancestry and 10,616 Swedish participants, alongside gene expression matrices from the Genotype-Tissue Expression (GTEx) Project. Validation of the significant genes was performed through three distinct methods: FUSION, FOCUS, and Multiple Marker Analysis of Genome-wide Annotation (MAGMA). Exploration of tissue and functional enrichment for FI-associated SNPs was conducted using MAGMA. Conditional and joint analyses, along with fine mapping, were employed to enhance our understanding of FI’s genetic architecture. Mendelian randomization was employed to ascertain causal relationships between significant genes and FI, and co-localization analysis was utilized to investigate shared SNPs between significant genes and FI.

Results: In this study, two novel susceptibility genes associated with the risk of FI were identified through the application of four TWAS methods. Mendelian randomization demonstrated that HTT may elevate the risk of developing frailty, whereas LRPPRC could offer protection against the onset of frailty. Additionally, co-localization analysis identified a shared SNP between LRPPRC and FI. Tissue enrichment analyses revealed that genomic regions linked to SNPs associated with frailty were predominantly enriched in various brain regions, including the frontal cortex, cerebral cortex, and cerebellar hemispheres. Conditional, combined analyses, and fine mapping collectively identified two genetic regions associated with frailty: 2p21 and 4q16.3. Functional enrichment analyses revealed that the pathways associated with frailty were primarily related to the MHC complex, PD-1 signaling, cognition, inflammatory response to antigenic stimuli, and the production of second messenger molecules.

Conclusion: This investigation uncovers two newly identified genes with forecasted expression levels associated with the risk of FI, offering new perspectives on the genetic architecture underlying FI.
Case report: A novel compound heterozygous variant in the COL4A3 gene was identified in a patient with autosomal recessive Alport syndrome
Authors: Chen Sha , Zhang Yufeng , He Jinjin , Yang Dingwei
Published: July 2024

Alport syndrome (AS), a hereditary kidney disease with a high risk for renal failure, is attributed to pathogenic variants in genes COL4A3, COL4A4, and COL4A5 that encode type IV collagen. Next-generation sequencing (NGS) is increasingly applied to the diagnosis of AS, but complex genotype–phenotype correlation, that is, identifying the significance of variants, is still a huge clinical challenge. In this study, we reported the case of a 27-year-old Chinese woman with a family history of hematuria and proteinuria. Notably, the proband is the only one in her family with renal insufficiency. NGS was performed in this family, and it was revealed that the proband was a compound heterozygote for two variants in the COL4A3 gene: c.2990G>A inherited from her father and c.4981C>T inherited from her mother. We modeled the spatial structure of the corresponding protein and assumed that structural abnormalities led to the breakdown of type IV collagen networks, a major component of the glomerular basement membrane. Thus, the proband was diagnosed with autosomal recessive AS, characterized by severe defects of the glomerular basement membrane. Hence, the proband showed a loss of renal function. This case presentation emphasizes the importance of NGS for AS diagnosis and introduces a novel genotype of AS.
Intergenerational consequences of violence: violence during pregnancy as a risk factor for infection in infancy
Authors: Blumrich Lukas , Sousa Braian Lucas Aguiar , Barbieri Marco Antônio , Simões Vanda Maria Ferreira , da Silva Antonio Augusto Moura , Bettiol Heloisa , Ferraro Alexandre Archanjo
Published: July 2024

Introduction

Psychosocial stress during pregnancy has long-lasting and important consequences in the following generations, as it can affect intrauterine development. The impact on the developing immune system is notoriously important due to the associated morbidity and mortality in the first years of life. Little attention has been given to the role of violence during pregnancy (VDP), especially its impact on infant infectious morbidity.

Methods

We analyzed data from two Brazilian birth cohorts (n = 2,847) in two distinct cities (Ribeirão Preto and São Luís), collected during pregnancy and at the beginning of the second year of life. The association between VDP and infection in infancy was analyzed with structural equation modeling, using the WHO-VAW questionnaire as exposure and a latent variable for infection as the outcome.

Results

VDP was reported by 2.48% (sexual), 11.56% (physical), and 45.90% (psychological) of the mothers. The models presented an adequate fit. In the city of São Luís, VDP was significantly associated with the latent construct for infection (standardized beta = 0.182; p = 0.022), while that was not the case for the Ribeirão Preto sample (standardized beta = 0.113; p = 0.113). Further analyses showed a gradient effect for the different dimensions of the exposure, from psychological to physical and sexual violence.

Conclusion

Our results suggest an association of VDP with infant morbidity in a poorer socioeconomic setting, and highlight the importance of considering the different dimensions of intimate partner violence. These findings may have important implications for the comprehension of global health inequalities and of the effects of gender-based violence.
Neutrophilic leukocytosis and erythema nodosum leprosum in leprosy: insights from a retrospective observational study
Authors: Feitosa da Silva Barboza Marcella , de Andrea Hacker Mariana , Maria Sales Anna , Fontoura Rodrigues Débora , Pedrosa Marques Daniel , José Ciryllo Silva Noya Danillo , Leal Silveira Andrezo Rosa Thabatta , de Fátima Alvim Braga Isabel , Ferreira Helen , Porto Amadeu Thais , Gurgel de Oliveira Monique , de Miranda Machado Alice , Illarramendi Ximena , Schmitz Veronica
Published: July 2024

Background

Leprosy reactions represent immunologically mediated episodes of acute inflammation that, if not diagnosed and treated promptly, can cause irreversible impairment of nerve function and permanent disabilities. A frequent type of reaction experienced by patients with lepromatous leprosy (LL) and borderline lepromatous leprosy (BL) is erythema nodosum leprosum (ENL), an inflammatory complication that may become chronic or recur in multiple episodes. Although ENL is commonly described as a neutrophil-mediated immune disease, the role of neutrophils is not fully understood. In this study, we assess neutrophilic leukocytosis in a retrospective cohort of patients affected by BL or LL leprosy.

Materials and methods

A retrospective observational study was performed using data from 146 patients with BL and LL leprosy diagnosed and treated at the Souza Araújo Outpatient Clinic, Fiocruz, Rio de Janeiro, Brazil. Clinical, demographic, and hematological data were extracted from medical records. Skin biopsy samples obtained from patients for ENL diagnosis were used for histopathological evaluations.

Results

Most patients were male (75%) and had a reactional episode (85%), of which 65% were ENL. Multiple episodes were common, 55% of the 80 patients with ENL presented more than 2 episodes (average of 2.6 episodes). In treatment-naive BL/LL patients, the median blood neutrophil counts of patients who developed ENL at some points of their disease course were higher than those who did not experience any reaction (median= 4,567 cells/mm3 vs 3,731 cells/mm3 respectively, p=0.0286). A correlation between the increase in median neutrophil counts and ENL severity was confirmed (6,066 cells/mm3 for mild ENL vs 10,243 cells/mm3 for moderate/severe ENL, p=0.0009). A longitudinal assessment was also performed in 34 patients, confirming the neutrophilic leukocytosis (BL/LL: 4896 cells/mm3 vs ENL: 8408 cells/mm3, p<0.0001). Moreover, increased NLR was associated with a greater neutrophilic infiltration in ENL lesions.

Conclusion

We demonstrate that ENL episodes in patients affected by leprosy are associated with elevated blood leukocyte and neutrophil counts and an increased NLR. These findings highlight the significant involvement of neutrophils in the ENL immunological/inflammatory process.
Exploration of ferroptosis and necroptosis-related genes and potential molecular mechanisms in psoriasis and atherosclerosis
Authors: Fan Jilin , Zhu Tingting , Tian Xiaoling , Liu Sijia , Zhang Shi-Liang
Published: July 2024

Objective

Ferroptosis and necroptosis are two recently identified forms of non-apoptotic cell death. Their dysregulation plays a critical role in the development and progression of Psoriasis (PsD) and Atherosclerosis (AS). This study explores shared Ferroptosis and necroptosis-related genes and elucidates their molecular mechanisms in PsD and AS through the analysis of public databases.

Methods

Data sets for PsD (GSE30999) and AS (GSE28829) were retrieved from the GEO database. Differential gene expression (DEG) and weighted gene co-expression network analysis (WGCNA) were performed. Machine learning algorithms identified candidate biomarkers, whose diagnostic values were assessed using Receiver Operating Characteristic (ROC) curve analysis. Additionally, the expression levels of these biomarkers in cell models of AS and PsD were quantitatively measured using Western Blot (WB) and real-time quantitative PCR (RT-qPCR). Furthermore, CIBERSORT evaluated immune cell infiltration in PsD and AS tissues, highlighting the correlation between characteristic genes and immune cells. Predictive analysis for candidate drugs targeting characteristic genes was conducted using the DGIdb database, and an lncRNA-miRNA-mRNA network related to these genes was constructed.

Results

We identified 44 differentially expressed ferroptosis-related genes (DE-FRGs) and 30 differentially expressed necroptosis-related genes (DE-NRGs). GO and KEGG enrichment analyses revealed significant enrichment of these genes in immune-related and inflammatory pathways, especially in NOD-like receptor and TNF signaling pathways. Two ferroptosis-related genes (NAMPT, ZFP36) and eight necroptosis-related genes (C7, CARD6, CASP1, CTSD, HMOX1, NOD2, PYCARD, TNFRSF21) showed high sensitivity and specificity in ROC curve analysis. These findings were corroborated in external validation datasets and cell models. Immune infiltration analysis revealed increased levels of T cells gamma delta, Macrophages M0, and Macrophages M2 in PsD and AS samples. Additionally, we identified 43 drugs targeting 5 characteristic genes. Notably, the XIST-miR-93–5p-ZFP36/HMOX1 and NEAT1-miR-93–5p-ZFP36/HMOX1 pathways have been identified as promising RNA regulatory pathways in AS and PsD.

Conclusion

The two ferroptosis-related genes (NAMPT, ZFP36) and eight necroptosis-related genes (C7, CARD6, CASP1, CTSD, HMOX1, NOD2, PYCARD, TNFRSF21) are potential key biomarkers for PsD and AS. These genes significantly influence the pathogenesis of PsD and AS by modulating macrophage activity, participating in immune regulation, and mediating inflammatory responses.
Exploring the impact of m6A modification on immune diseases: mechanisms and therapeutic implication
Authors: Chen Yutong , Liu Min , Lu Miao , Luo Linling , Han Zhongyu , Liu Xide
Published: July 2024

N6-methyladenosine (m6A) is a chemical modification of RNA and has become a widely discussed topic among scientific researchers in recent years. It is distributed in various organisms, including eukaryotes and bacteria. It has been found that m6A is composed of writers, erasers and readers and is involved in biological functions such as splicing, transport and translation of RNA. The balance of the human immune microenvironment is important for human health abnormalities. Increasing studies have found that m6A affects the development of immune diseases such as inflammatory enteritis and systemic lupus erythematosus (SLE) by participating in the homeostatic regulation of the immune microenvironment in vivo. In this manuscript, we introduce the composition, biological function, regulation of m6A in the immune microenvironment and its progression in various immune diseases, providing new targets and directions for the treatment of immune diseases in clinical practice.
Intravascular large B-cell lymphoma as a covert trigger for hemophagocytic lymphohistiocytosis complicated with capillary leak syndrome: a case report and literature review
Authors: Wen Jingjing , Xu Juan , Ji Jie , Zhang Wenyan , Zheng Qin , Liu Ting , Zheng Yuhuan , Ma Hongbing
Published: July 2024

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of non-Hodgkin lymphoma. Patients with hemophagocytic lymphohistiocytosis (HLH)-associated IVLBCL variants exhibit significantly poor survival. Cytokines play pivotal roles in malignancy-associated HLH as well as in capillary leak syndrome (CLS). The pathogenesis of CLS involves hyperpermeability and transient endothelial dysfunction. Here, we report the first case of HLH-associated IVLBCL variant complicated with CLS. The patient presented with fever, refractory hypoproteinemia, hypotension and severe edema, followed by telangiectasias. Treatment with etoposide and dexamethasone and hydroxyethyl starch-based artificial colloid led to transient improvement. The diagnosis of IVLBCL was confirmed after the sixth bone marrow biopsy. Subsequently, the R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisolone) regimen was administered and resulted in prompt alleviation of CLS and HLH symptoms. The patient has survived for more than 6 years after combination of immunochemotherapy and autologous peripheral stem-cell transplantation. This case provides some insights into the mechanism and clinical management of IVLBCL complicated with HLH and CLS. Similar cases concerning lymphoma-associated CLSs were also reviewed.
Application of CD25 and CTLA4 gene transcription levels in early prediction of acute graft-versus-host disease
Authors: Huang Ken , Yang Mengxin , Zhou Yuhang , Cao Yaxuan , Pang Guanxiu , Zhao Jie , Liu Yang , Luo Jianming
Published: July 2024

Introduction

Our study investigated the potential of peripheral blood T cell CD25, CD28, and CTLA-4 gene transcription levels as predictive biomarkers for acute graft-versus-host disease (aGVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Methods

Real-time reverse transcription fluorescent quantitative PCR (RT-qPCR) analysis was conducted on day +7, +14, and +21 post-transplantation in patients undergoing allo-HSCT.

Results

Elevated levels of CD25 and CTLA-4 mRNA were found to be associated with the occurrence of aGVHD, as well as severe and gastrointestinal aGVHD. Receiver operating characteristic (ROC) curve analysis was utilized to assess the predictive value of each biomarker. Combined analysis of CD25 and CTLA-4 mRNA levels demonstrated promising predictive potential for aGVHD.

Conclusion

Our results confirmed that the transcription levels of CD25 and CTLA-4 genes could be used as early predictive biomarkers for aGVHD post-allo-HSCT.
Relationship between the complement system and serum lipid profile in patients with rheumatoid arthritis
Authors: Rodríguez-González Dara , García-González María , Gómez-Bernal Fuensanta , Quevedo-Abeledo Juan C. , González-Rivero Agustín F. , Jiménez-Sosa Alejandro , González-López Elena , Heras-Recuero Elena , Ocejo-Vinyals J. Gonzalo , González-Gay Miguel Á. , Ferraz-Amaro Iván
Published: July 2024

Background

The complement system has been linked to the etiopathogenesis of rheumatoid arthritis (RA). Patients with RA exhibit a dysregulated profile of lipid molecules, which has been attributed to the inflammation present in the disease. In this study, we aimed to evaluate the association between a comprehensive assessment of the complement system and the lipid profile of patients with RA.

Methods

430 patients with RA were recruited. New-generation techniques were employed to conduct functional assays of the three pathways of the complement system. Serum levels of various complement components such as C1q, factor D, properdin, lectin, C1-inhibitor, C2, C4, C4b, C3, C3a, C5, C5a, and C9 were assessed. Furthermore, a complete pattern of lipid molecules was measured including high (HDL), low-density lipoproteins (LDL), and lipoprotein (a). Multivariable linear regression analysis was conducted to investigate the association between the complement system and lipid profile in RA patients.

Results

After multivariable analysis, several noteworthy associations emerged between the complement system and lipid molecules. Notably, complement components most strongly linked to the lipid profile were C1q and properdin, representing the upstream classical and alternative pathways, along with C3 from the common cascade. These associations demonstrated significance and positivity concerning total cholesterol, LDL, atherogenic index, apolipoprotein B, and lipoprotein(a), suggesting a connection with an unfavorable lipid profile. Interestingly, complement functional assays of the three pathways and activated products such as C3a and C5a showed no correlation with the lipid pattern.

Conclusion

The correlation between the complement system and lipid molecule patterns is pronounced in patients with RA. This relationship is predominantly positive and primarily associated with upstream complement components rather than activated ones.
Targeting the tumor microenvironment to improve clinical outcomes in triple negative breast cancer patients and bridge the current disparity gap
Authors: Alharbi Malak , Roy Arya Mariam , Krishnan Jayasree , Kalinski Pawel , Yao Song , Gandhi Shipra
Published: July 2024

Triple negative breast cancer (TNBC) is a heterogenous disease that disproportionately affects Black women. TNBC outcomes among Black women are dismal secondary to multiple factors, such as poor healthcare accessibility resulting in delays in diagnosis, and aggressive disease biology in addition to a pro-tumor immune microenvironment (TME). Black women with breast cancer exhibit elevated levels of serum pro-inflammatory cytokines, and a pro-tumorigenic TME with higher immunosuppressive regulatory T cells (Tregs), M2 macrophages and exhausted CD8+ T cells. We have shown that the combined use of toll-like receptor 3 (TLR3) ligands with interferon-α (chemokine modulation: CKM) is able to enrich the tumor with CD8+ T cells, while not increasing immunosuppressive cells. Recent clinical trials have revealed the efficacy of immune checkpoint inhibitors (ICI) in rejuvenizing exhausted CD8+ T cells. We hypothesize that strategies to modulate the TME by enriching chemokines that attract CD8+T cells followed by reversal of CD8+ T cell exhaustion (ICI), when added to standard treatment, could potentially improve clinical outcomes, and mitigate the racial disparities in TNBC outcomes between Black and White Women.
The role of CD8 PET imaging in guiding cancer immunotherapy
Authors: Zhang Jiani , Du Bulin , Wang Yuxiang , Cui Yan , Wang Shu , Zhao Yuxuan , Li Yaming , Li Xuena
Published: July 2024

Currently, immunotherapy is being widely used for treating cancers. However, the significant heterogeneity in patient responses is a major challenge for its successful application. CD8-positive T cells (CD8+ T cells) play a critical role in immunotherapy. Both their infiltration and functional status in tumors contribute to treatment outcomes. Therefore, accurate monitoring of CD8+ T cells, a potential biomarker, may improve therapeutic strategy. Positron emission tomography (PET) is an optimal option which can provide molecular imaging with enhanced specificity. This review summarizes the mechanism of action of CD8+ T cells in immunotherapy, and highlights the recent advancements in PET-based tracers that can visualize CD8+ T cells and discusses their clinical applications to elucidate their potential role in cancer immunotherapy.
On the generalization discrepancy of spatiotemporal dynamics-informed graph convolutional networks
Authors: Sun Yue , Chen Chao , Xu Yuesheng , Xie Sihong , Blum Rick S. , Venkitasubramaniam Parv
Published: July 2024

Graph neural networks (GNNs) have gained significant attention in diverse domains, ranging from urban planning to pandemic management. Ensuring both accuracy and robustness in GNNs remains a challenge due to insufficient quality data that contains sufficient features. With sufficient training data where all spatiotemporal patterns are well-represented, existing GNN models can make reasonably accurate predictions. However, existing methods fail when the training data are drawn from different circumstances (e.g., traffic patterns on regular days) than test data (e.g., traffic patterns after a natural disaster). Such challenges are usually classified under domain generalization. In this work, we show that one way to address this challenge in the context of spatiotemporal prediction is by incorporating domain differential equations into graph convolutional networks (GCNs). We theoretically derive conditions where GCNs incorporating such domain differential equations are robust to mismatched training and testing data compared to baseline domain agnostic models. To support our theory, we propose two domain-differential-equation-informed networks: Reaction-Diffusion Graph Convolutional Network (RDGCN), which incorporates differential equations for traffic speed evolution, and the Susceptible-Infectious-Recovered Graph Convolutional Network (SIRGCN), which incorporates a disease propagation model. Both RDGCN and SIRGCN are based on reliable and interpretable domain differential equations that allow the models to generalize to unseen patterns. We experimentally show that RDGCN and SIRGCN are more robust with mismatched testing data than state-of-the-art deep learning methods.
Detection of natural autoimmunity to ghrelin in diabetes mellitus
Authors: Kasim Rega H. , Chillon Thilo Samson , Eleftheriadou Anna Maria , Rijntjes Eddy , Minich Waldemar B. , Zechmann Stefan , Schomburg Lutz
Published: July 2024

Objective

Ghrelin is an orexigenic peptide that becomes post-translationally modified. Natural autoantibodies to ghrelin (ghrelin-aAb) have been described in healthy subjects, in eating disorders and rheumatic diseases, with potential clinical relevance. Despite these important reports, the data base on the prevalence and physiological role is small and technical approaches for assessing ghrelin-aAb are few, encouraging respective research for improving knowledge on the potential endocrine significance.

Methods

A novel immunoprecipitation assay was generated based on a fusion protein of human ghrelin with a reporter gene. Assay quality was verified with commercial antibodies. Assay characteristics and matrix effects were determined, including stability of natural ghrelin-aAb to freezing, signal linearity in dilution experiments, and comparison of different matrices. Three groups of serum samples were analyzed for ghrelin-aAb, comprising commercial sera from healthy subjects and patients with type 1 or type 2 diabetes mellitus.

Results

The newly generated ghrelin-aAb assay proved sensitive, robust and reliable over a broad concentration range. Results from serum and plasma differed slightly. The signals from serum remained stable towards freezing and thawing, and in dilution experiments. Applying a mathematical criterion for outliers (P75 + 1.5-times IQR), an average prevalence of 11%–12% of positive samples was identified in the different human cohorts, with no significant sex-or disease-related difference.

General significance

A novel diagnostic autoantibody assay detected ghrelin-aAb with a similar prevalence in diabetic patients and controls, suggesting that autoimmunity to ghrelin plays little role in diabetes mellitus, but may be of relevance in other diseases where ghrelin signaling is essential.
Changes in sediment greenhouse gases production dynamics in an estuarine wetland following invasion by Spartina alterniflora
Authors: Jiang Yongcan , Shao Yinlong , Huang Jiafang , Du Yunling , Wen Yu , Tang Hong , Xu Jianming , Gao Dengzhou , Lin Xianbiao , Sun Dongyao
Published: July 2024

Invasive Spartina alterniflora (S. alterniflora) has significant impacts on sediment biogeochemical cycling in the tidal wetlands of estuaries and coasts. However, the impact of exotic Spartina alterniflora invasion on greenhouse gases (GHGs) production dynamics in sediments remain limited. Here, we investigated the dynamics of sediment physicochemical properties, GHGs production rates, and microbial gene abundances in a native Cyperus malacensis habitat and three invasive S. alterniflora habitats (6-, 10-, and 14-year) in the Minjiang River Estuary, China. The methane (CH4), carbon dioxide (CO2), and nitrous oxide (N2O) production rates varied both spatially and seasonally, while microbial gene abundances (bacterial and fungal gene abundances) and organic matter (TOC and TN) only varied spatially. GHGs production rates were also characterized by higher values in surface sediment (0–10 cm) compared to subsurface sediment (10–20 cm) and by seasonal variations with higher values in summer than in winter. S. alterniflora invasion can significantly increase CH4 and CO2 production rates, organic matter, and microbial gene abundances (p < 0.05). Temperature, organic matter and microbial gene abundances were the most dominating factor controlling the spatio-temporal variations of CH4 and CO2 production rates. Overall, our findings highlighted the significant role of S. alterniflora invasion in regulating GHGs production rates in coastal wetland sediments and provided fundamental data for estimating GHGs emissions and carbon sequestration in the complex tidal wetlands.
The causal relationship between gut microbiota and alopecia areata: a Mendelian randomization analysis
Authors: Bi Dezhao , Tey Jin Tong , Yao Dan , Cao Yutian , Qian Minyu , Shi Jianxin , Guo Shun
Published: July 2024

Background

Increasing evidence suggests a robust correlation between the gut microbiome and alopecia areata. In light of the extensive diversity of gut microbiota, this study aims to utilize state-of-the-art and comprehensive data to explore the causative association between gut microbiota and alopecia areata.

Objective

We conducted a Mendelian randomization (MR)-based two-sample study to elucidate the causal relationship between gut microbiota and alopecia areata.

Method

Summary information on Ncase = 767 and Ncontrol = 394,105 cases of alopecia areata was obtained from the FinnGen study. A total of 473 gut microbial taxa were summarized from the genome-wide association study (GWAS) catalog. The study comprised a forward Mendelian randomization (MR) analysis with the gut microbiome as the exposure factor and alopecia areata as the outcome, as well as a reverse MR analysis with alopecia areata as the exposure factor and the gut microbiome as the outcome. Various analytical methods including inverse variance weighting (IVW), Weighted Median, MR-Egger, Weighted Mode, and Simple Mode were employed. Subsequently, sensitivity analysis was conducted to ensure the robustness of our research findings.

Result

This study has established a causal relationship between gut microbiota and alopecia areata. Forward causal analysis revealed causality relationships between 16 gut microbial taxa and alopecia areata, while reverse causal analysis found that there may be a causal relationship between alopecia areata and 16 gut microbial taxa (not statistically significant).

Conclusion

Our study findings suggest a causal relationship between gut microbiota and alopecia areata, providing potential guidance for future clinical trials.
Artificial intelligence tools for the identification of antibiotic resistance genes
Authors: Olatunji Isaac , Bardaji Danae Kala Rodriguez , Miranda Renata Rezende , Savka Michael A. , Hudson André O.
Published: July 2024

The fight against bacterial antibiotic resistance must be given critical attention to avert the current and emerging crisis of treating bacterial infections due to the inefficacy of clinically relevant antibiotics. Intrinsic genetic mutations and transferrable antibiotic resistance genes (ARGs) are at the core of the development of antibiotic resistance. However, traditional alignment methods for detecting ARGs have limitations. Artificial intelligence (AI) methods and approaches can potentially augment the detection of ARGs and identify antibiotic targets and antagonistic bactericidal and bacteriostatic molecules that are or can be developed as antibiotics. This review delves into the literature regarding the various AI methods and approaches for identifying and annotating ARGs, highlighting their potential and limitations. Specifically, we discuss methods for (1) direct identification and classification of ARGs from genome DNA sequences, (2) direct identification and classification from plasmid sequences, and (3) identification of putative ARGs from feature selection.