bluuebunny/crossref_metadata_2025 huggingface dataset:
Additive effects of type 2 diabetes and metabolic syndrome on left ventricular torsion and linear deformation abnormalities during dobutamine stress echocardiography
Authors: Aboukhoudir Falah , Philouze Clothilde , Grandperrin Antoine , Nottin Stéphane , Obert Philippe
Published: September 2022

Objective

The interplay between metabolic syndrome (MS) and type 2 diabetes (T2D) on regional myocardial mechanics and the potential additional effects of their combination remain poorly understood. In this context, we evaluated left ventricular (LV) torsion and linear deformation at rest and under dobutamine (DB) stress in patients with T2D, MS or both.

Methods

Thirty-nine T2D patients without MS (T2D), 37 MS patients free from T2D (MS), 44 patients with both T2D and MS (T2D-MS group) and 38 healthy patients (control group) were prospectively recruited. Speckle-tracking echocardiography (STE) was conducted at rest and low dose DB to evaluate LV myocardial longitudinal (LS) as well as circumferential (CS) strain and early diastolic strain rate (LSrd, CSrd) and twist-untwist mechanics.

Results

At rest, MS, T2D and controls presented with similar resting LS and LSrd while significant lower values were obtained in T2D-MS compared to controls. DB revealed reduced LS, LSrd, CS and CSrd in MS and T2D groups compared to controls. In T2-MS, the decline in LS and LSrd established at rest was exacerbated under DB. Stress echocardiography revealed also lower basal rotation and subsequently lower twist in MS and T2D patients compared to controls. T2D-MS showed major impairments of apical rotation and twist under DB stress, with values significantly lower compared to the 3 other groups. From stepwise multiple linear regression analysis, epicardial adipose tissue for Δ (rest to DB) LS, numbers of MS factors for Δ CS and Δ Twist emerged as major independent predictors.

Conclusion

These results demonstrate synergic and additive effects of T2D and MS on LV torsion and linear deformation abnormalities in asymptomatic patients with metabolic diseases. They also highlight the usefulness of speckle tracking echocardiography under DB stress in detecting multidirectional myocardial mechanics impairments that can remain barely detectable at rest, such as in isolated T2D or MS patients.
Possible links with methane seepage and gas hydrate dynamics inferred from authigenic barite records in the northern south china sea
Authors: Feng Junxi , Luo Min , Liang Jinqiang , Yang Shengxiong , Wang Hongbin , Li Niu , Sun Xiaoming
Published: September 2022

Numerous methane seepage events occurred in periods of low or falling sea level since 330 ka BP, which is attributed to decrease in hydrostatic pressure and subsequent gas hydrate dissociation in the northern South China Sea (SCS). The seepage intensity likely decrease due to gas hydrate stabilization once there was a relatively high-stand sea level. However, there are few geochemical records of decline in upward methane flux in the northern South China Sea. Here, combing porewater and solid-phase analyses, the geochemical cycling of barium was investigated in two piston cores from sites HD109 and HD319 within two areas with inferred gas hydrate occurrence in the Taixinan Basin of the northern SCS, in order to track the net decrease in the upward methane flux and to estimate the total duration time of these events in the studied sediments. The results indicate that there are four intervals with barium enrichments in the sediment section overlying the occurrent sulfate-methane transition zone (SMTZ) at both cores, suggesting the SMTZs have downward migrated through time. Based on the excess barium contents and the diffusive Ba2+ fluxes above the current SMTZ, we estimate the total time for barium accumulation at both cores is about ten thousand years. It is suggested that some methane seepage events temporarily enhance the upward flux of methane, inducing anaerobic oxidation of methane and associated SMTZ close to the sediment surface before the Holocene. After the most intensive seepage event ceased in the post-glacial period, the upward methane flux decreased and the SMTZ migrated downward gradually, preserving enrichments of diagenetic barite. Overall, these new data confirm the episodic decrease in upward methane flux recorded by authigenic barite after the last glacial maximum, which is likely related to the stabilization of underlying gas hydrate reservoir. This study may fill in the gap of the geochemical records of the variations in methane seepage and gas hydrate system during the post-glacial period in the northern SCS.
Experimental investigation of pore structure and its influencing factors of marine-continental transitional shales in southern Yan’an area, ordos basin, China
Authors: Xiao Hui , Xie Nan , Lu Yuanyuan , Cheng Tianyue , Dang Wei
Published: September 2022

The intensive study of the pore structure and its controlling factors of shale reservoir has important guiding significance for further exploration and exploitation of shale gas. This work investigated the effects of organic and inorganic compositions on the development of pore structures of the Upper Permian Shanxi shale in the southern Yan’an area, Ordos Basin. Based on the results of high-pressure mercury intrusion, low-pressure N2 and CO2 adsorption and organic geochemical experiments, X-ray diffraction and scanning electron microscope observations, the mineral composition, pore structure and its influencing factors of the transitional shale were studied systematically. The results indicate that the total organic carbon (TOC) content of the shale is between 0.12% and 5.43%, with an average of 1.40%. The type of the organic matter (OM) belongs to Type III and has over maturity degree with an average Ro of 2.54%. An important character of this kind of shale is the large proportion of clay mineral content, which ranges from 40.70% to 87.00%, and with an average of 60.05%. Among them, illite and kaolinite are the main components, and they account for 36.6% and 36.7% of the total clay minerals respectively, followed by chlorite and illite/smectite (I/S) mixed layer. The quartz content is between 10.6% and 54.5%, with an average of 35.49%. OM (organic matter) pores are mostly circular bubble-shaped pores, and most of them are micropores, while inorganic pores are well developed and mainly contributed by clay mineral pores and have slit-type, plate-like and irregular polygon forms. Mesopores are the major contributor to pore volume (PV), while micropores contribute the least to PV. The contribution of micropores to the specific surface area (SSA) is greater than 61%, followed by mesopores. Macropores have almost no contribution to the development of SSA. OM pores are the main contributor to the total specific surface area of the shale, with an average contribution rate of 61.05%, but clay mineral pores contribute more to the total pore volumes. In addition, both the content of chlorite and illite/smectite (I/S) mixed layer is positively correlated with the volume ratio of mesopores. It was found that high TOC, I/S mixed layer and chlorite content are all favorable conditions for the target shale.
Development and validation of a nomogram for assessing risk of isolated high 2-hour plasma glucose
Authors: Sun Kan , Xiao Xianchao , You Lili , Hong Xiaosi , Lin Diaozhu , Liu Yujia , Huang Chulin , Wang Gang , Li Feng , Sun Chenglin , Chen Chaogang , Lu Jiahui , Qi Yiqin , Wang Chuan , Li Yan , Xu Mingtong , Ren Meng , Yang Chuan , Wang Guixia , Yan Li
Published: September 2022

A tool was constructed to assess need of an oral glucose tolerance test (OGTT) in patients whose fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) are normal. Data was collected from the longitudinal REACTION study conducted from June to November 2011 (14,686 subjects, aged ≥ 40 y). In people without a prior history of diabetes, isolated high 2-hour plasma glucose was defined as 2-hour plasma glucose ≥ 11.1 mmol/L, FPG < 7.0 mmol/L, and HbA1c < 6.5%. A predictive nomogram for high 2-hour plasma glucose was developed via stepwise logistic regression. Discrimination and calibration of the nomogram were evaluated by the area under the receiver operating characteristic curve (AUC) and Hosmer-Lemeshow test; performance was externally validated in Northeast China. Parameters in the model included gender, age, drinking status, marriage status, history of hypertension and hyperlipidemia, waist-to-hip ratio, FPG, and HbA1c. All variables were noninvasive, except FPG and HbA1c. The AUC of the nomogram for isolated high 2-hour plasma glucose was 0.759 (0.727-0.791) in the development dataset. The AUCs of the internal and externally validation datasets were 0.781 (0.712-0.833) and 0.803 (0.778-0.829), respectively. Application of the nomogram during the validation study showed good calibration, and the decision curve analysis indicated that the nomogram was clinically useful. This practical nomogram model may be a reliable screening tool to detect isolated high 2-hour plasma glucose for individualized assessment in patients with normal FPG and HbA1c. It should simplify clinical practice, and help clinicians in decision-making.
Lipoprotein sialylation in atherosclerosis: Lessons from mice
Authors: Yu Liming , Peng Jun , Mineo Chieko
Published: September 2022

Sialylation is a dynamically regulated modification, which commonly occurs at the terminal of glycan chains in glycoproteins and glycolipids in eukaryotic cells. Sialylation plays a key role in a wide array of biological processes through the regulation of protein–protein interactions, intracellular localization, vesicular trafficking, and signal transduction. A majority of the proteins involved in lipoprotein metabolism and atherogenesis, such as apolipoproteins and lipoprotein receptors, are sialylated in their glycan structures. Earlier studies in humans and in preclinical models found a positive correlation between low sialylation of lipoproteins and atherosclerosis. More recent works using loss- and gain-of-function approaches in mice have revealed molecular and cellular mechanisms by which protein sialylation modulates causally the process of atherosclerosis. The purpose of this concise review is to summarize these findings in mouse models and to provide mechanistic insights into lipoprotein sialylation and atherosclerosis.
Carbon neutrality cognition, environmental value, and consumption preference of low-carbon products
Authors: Li Baoku , Nan Yafeng , Yao Ruoxi
Published: September 2022

It is now the mainstream scientific consensus that carbon emissions cause global climate change. Achieving the goal of China’s carbon neutrality is essential for environmental protection and economic sustainable development worldwide. In the above context, this paper aims to explore the carbon neutrality cognition, environmental value, and consumption preference for low-carbon products from the perspective of consumption end. Thus, we built and checked a new conceptual model of consumers’ carbon neutrality cognition and the consumption preference for low-carbon products. The TF-IDF algorithm in machine learning was used to confirm the dimensions of carbon neutrality cognition based on text data collected from an academic database CNKI. Then, we used data from a social investigation (N = 405) to test hypotheses and models using bootstrapping and independent sample t-tests. The results showed that altruistic (β = 0.168, 95% CI: [−0.54514, 0.8819]) and egoistic values (β = −0.066, 95% confidence interval [CI]: [−0.6361, 0.6772]) mediated the impact of carbon neutrality cognition on the consumption of low-carbon products, whereas the egoistic value did not (β = −0.066, 95% CI: [−0.6361, 0.6772]). Additionally, based on the characteristics of current Chinese consumers and the market, we argue for two boundary factors: face consciousness and carbon footprint label. The moderation of face consciousness (Mhigh = 5.395 vs. Mlow = 3.312) and carbon footprint label (Mwith = 6.394 vs. Mwithout = 5.432) were revealed. The empirical results support our conceptual model, and our findings provide insights to policymakers and enterprises regarding people’s carbon neutrality cognition, which will allow them to develop more appropriate policies and sustainable development strategies.
Experimental short-time wildfire simulation—Physicochemical changes of forest mucky topsoil
Authors: Kupka Dawid , Khan Muhammad Owais , Kwika Agata , Słowik-Opoka Ewa , Klamerus-Iwan Anna
Published: September 2022

Today, fires constitute one of the most important factors that can affect soil properties, acting at a rapid pace and on a large scale. They often result from climate change. The present study was aimed at examining how water capacity as well as carbon and nitrogen concentration change during a simulated fire of forest mucky soil under laboratory conditions. The combustion was carried out in two short-time variants—for 3 and 9 min. The results presented herewith show that even a short-term fire of the soil cover contributes to visible changes in the physicochemical parameters of the soil. Thermal decomposition of organic matter caused an increase in total carbon and nitrogen concentrations and a slight increase in the Ct/Nt ratio. The burning of soil samples caused a slight upward trend in soil pH and this was associated with soil organic matter (SOM) deprotonation. The experiment showed the effect of mucky soil burning on the change of its water relations. The 3-min combustion significantly increased the maximum water storage capacity (both after 4 and after 24 h of immersion in water), while the 9-min combustion showed significantly worse results.
AntiVIRmiR: A repository of host antiviral miRNAs and their expression along with experimentally validated viral miRNAs and their targets
Authors: Thakur Anamika , Kumar Manoj
Published: September 2022

miRNAs play an essential role in promoting viral infections as well as modulating the antiviral defense. Several miRNA repositories have been developed for different species, e.g., human, mouse, and plant. However, ‘VIRmiRNA’ is the only existing resource for experimentally validated viral miRNAs and their targets. We have developed a ‘AntiVIRmiR’ resource encompassing data on host/virus miRNA expression during viral infection. This resource with 22,741 entries is divided into four sub-databases viz., ‘DEmiRVIR’, ‘AntiVmiR’, ‘VIRmiRNA2’ and ‘VIRmiRTar2’. ‘DEmiRVIR’ has 10,033 differentially expressed host-viral miRNAs for 21 viruses. ‘AntiVmiR’ incorporates 1,642 entries for host miRNAs showing antiviral activity for 34 viruses. Additionally, ‘VIRmiRNA2’ includes 3,340 entries for experimentally validated viral miRNAs from 50 viruses along with 650 viral isomeric sequences for 14 viruses. Further, ‘VIRmiRTar2’ has 7,726 experimentally validated targets for viral miRNAs against 21 viruses. Furthermore, we have also performed network analysis for three sub-databases. Interactions between up/down-regulated human miRNAs and viruses are displayed for ‘AntiVmiR’ as well as ‘DEmiRVIR’. Moreover, ‘VIRmiRTar2’ interactions are shown among different viruses, miRNAs, and their targets. We have provided browse, search, external hyperlinks, data statistics, and useful analysis tools. The database available at https://bioinfo.imtech.res.in/manojk/antivirmir would be beneficial for understanding the host-virus interactions as well as viral pathogenesis.
Sarcomatoid-associated gene risk index for clear cell renal cell carcinoma
Authors: Zuo You , Fu Shuai , Zhao Zhongwei , Li Zeyan , Wu Yijian , Qi Tienan , Zheng Jianguo , Du Qinglong , Xu Zhonghua , Yu Nengwang
Published: September 2022

Sarcomatoid renal cell carcinoma is a de-differentiated form of kidney cancer with an extremely poor prognosis. Genes associated with sarcomatoid differentiation may be closely related to the prognosis of renal cell carcinoma. The prognosis of renal cell carcinoma itself is extremely variable, and a new prognostic model is needed to stratify patients and guide treatment. Data on clear cell renal cell carcinoma with or without sarcomatoid differentiation were obtained from TCGA database, and a sarcomatoid-associated gene risk index (SAGRI) and column line graphs were constructed using sarcomatoid-associated genes. The predictive power of the SAGRI and column line graphs was validated using an internal validation set and an independent validation set (E-MTAB-1980). The SAGRI was constructed using four sarcoma-like differentiation-related genes, COL7A1, LCTL, NPR3, ZFHX4, and had a 1-year AUC value of 0.725 in the training set, 0.712 in the internal validation set, and 0.770 in the independent validation set for TCGA training cohort, with high model reliability. The molecular characteristics among the SAGRI subgroups were analyzed by multiple methods, and results suggested that the SAGRI-HIGH subgroup may benefit more from immunotherapy to improve prognosis. SAGRI satisfactorily predicted the prognosis of patients with clear cell renal cell carcinoma with or without sarcomatoid differentiation.
Bioinformatic analysis and experimental validation identified DNA methylation–Related biomarkers and immune-cell infiltration of atherosclerosis
Authors: Xu Congjian , Sun Di , Wei Changmin , Chang Hao
Published: September 2022

Background: DNA methylation is an important form of epigenetic regulation and is closely related to atherosclerosis (AS). The purpose of this study was to identify DNA methylation–related biomarkers and explore the immune-infiltrate characteristics of AS based on methylation data.

Methods: DNA methylation data of 15 atherosclerotic and paired healthy tissues were obtained from Gene Expression Omnibus database. Differential methylation positions (DMPs) and differential methylation regions (DMRs) were screened by the ChAMP R package. The methylation levels of DMPs located on CpG islands of gene promoter regions were averaged. The limma R package was used to screen differentially methylated genes in the CpG islands of the promoter regions. The diagnostic values of the methylation levels were evaluated using the pROC R package. The EpiDISH algorithm was applied to quantify the infiltration levels of seven types of immune cells. Subsequently, three pairs of clinical specimens of coronary atherosclerosis with Stary’s pathological stage III were collected, and the methylation levels were detected by the methylation-specific PCR (MS-PCR) assay. Western blot was performed to detect the protein expression levels of monocyte markers.

Results: A total of 110, 695 DMPs, and 918 DMRs were screened in the whole genome. Also, six genes with significant methylation differences in the CpG islands of the promoter regions were identified, including 49 DMPs. In total, three genes (GRIK2, HOXA2, and HOXA3) had delta beta greater than 0.2. The infiltration level of monocytes was significantly upregulated in AS tissues. MS-PCR assay confirmed the methylation status of the aforementioned three genes in AS samples. The Western blot results showed that the expression levels of the monocyte marker CD14 and M1-type macrophage marker CD86 were significantly increased in AS while M2-type macrophage marker protein CD206 was significantly decreased.

Conclusion: This study identified potential DNA methylation–related biomarkers and revealed the role of monocytes in early AS.
Profiling genes encoding the adaptive immune receptor repertoire with gAIRR Suite
Authors: Lin Mao-Jan , Lin Yu-Chun , Chen Nae-Chyun , Luo Allen Chilun , Lai Sheng-Kai , Hsu Chia-Lang , Hsu Jacob Shujui , Chen Chien-Yu , Yang Wei-Shiung , Chen Pei-Lung
Published: September 2022

Adaptive immune receptor repertoire (AIRR) is encoded by T cell receptor (TR) and immunoglobulin (IG) genes. Profiling these germline genes encoding AIRR (abbreviated as gAIRR) is important in understanding adaptive immune responses but is challenging due to the high genetic complexity. Our gAIRR Suite comprises three modules. gAIRR-seq, a probe capture-based targeted sequencing pipeline, profiles gAIRR from individual DNA samples. gAIRR-call and gAIRR-annotate call alleles from gAIRR-seq reads and annotate whole-genome assemblies, respectively. We gAIRR-seqed TRV and TRJ of seven Genome in a Bottle (GIAB) DNA samples with 100% accuracy and discovered novel alleles. We also gAIRR-seqed and gAIRR-called the TR and IG genes of a subject from both the peripheral blood mononuclear cells (PBMC) and oral mucosal cells. The calling results from these two cell types have a high concordance (99% for all known gAIRR alleles). We gAIRR-annotated 36 genomes to unearth 325 novel TRV alleles and 29 novel TRJ alleles. We could further profile the flanking sequences, including the recombination signal sequence (RSS). We validated two structural variants for HG002 and uncovered substantial differences of gAIRR genes in references GRCh37 and GRCh38. gAIRR Suite serves as a resource to sequence, analyze, and validate germline TR and IG genes to study various immune-related phenotypes.
Causal effects of gut microbiota on diabetic retinopathy: A Mendelian randomization study
Authors: Liu Kangcheng , Zou Jing , Fan Huimin , Hu Hanying , You Zhipeng
Published: September 2022

Background

Previous researches have implicated a vital association between gut microbiota (GM) and diabetic retinopathy (DR) based on the association of the “gut-retina” axis. But their causal relationship has not been elucidated.

Methods

Instrumental variables of 211 GM taxa were obtained from genome wide association study (GWAS), and Mendelian randomization study was carried out to estimate their effects on DR risk from FinnGen GWAS (14,584 DR cases and 202,082 controls). Inverse variance weighted (IVW) is the main method to analyze causality, and MR results are verified by several sensitive analyses.

Results

As for 211 GM taxa, IVW results confirmed that family-Christensenellaceae (P = 1.36×10-2) and family-Peptococcaceae (P = 3.13×10-2) were protective factors for DR. Genus-Ruminococcaceae_UCG_011 (P = 4.83×10-3), genus-Eubacterium_rectale_group (P = 3.44×10-2) and genus-Adlercreutzia (P = 4.82×10-2) were correlated with the risk of DR. At the phylum, class and order levels, we found no GM taxa that were causally related to DR (P>0.05). Heterogeneity (P>0.05) and pleiotropy (P>0.05) analysis confirmed the robustness of MR results.

Conclusion

We confirmed that there was a potential causal relationship between some GM taxa and DR, which highlights the association of the “gut-retina” axis and offered new insights into the GM-mediated mechanism of DR. Further explorations of their association are required and will lead to find new biomarkers for targeted prevention strategies of DR.
Are higher antibody levels against seasonal human coronaviruses associated with a more robust humoral immune response after SARS-CoV-2 vaccination?
Authors: Asamoah-Boaheng Michael , Grunau Brian , Karim Mohammad Ehsanul , Jassem Agatha N. , Bolster Jennifer , Marquez Ana Citlali , Scheuermeyer Frank X. , Goldfarb David M.
Published: September 2022

The SARS-CoV-2 belongs to the coronavirus family, which also includes common endemic coronaviruses (HCoVs). We hypothesized that immunity to HCoVs would be associated with stronger immunogenicity from SARS-CoV-2 vaccines. The study included samples from the COSRIP observational cohort study of adult paramedics in Canada. Participants provided blood samples, questionnaire data, and results of COVID-19 testing. Samples were tested for anti-spike IgG against SARS-CoV-2, HCoV-229E, HCoV-HKU1, HCoV-NL63, and HCoV-OC43 antigens. We first compared samples from vaccinated and unvaccinated participants, to determine which HCoV antibodies were affected by vaccination. We created scatter plots and performed correlation analysis to estimate the extent of the linear relationship between HCoVs and SARS-CoV-2 anti-spike antibodies. Further, using adjusted log-log multiple regression, we modeled the association between each strain of HCoV and SARS-CoV-2 antibodies. Of 1510 participants (mean age of 39 years), 94 (6.2%) had a history of COVID-19. There were significant differences between vaccinated and unvaccinated participant in anti-spike antibodies to HCoV-HKU1, and HCoV-OC43; however, levels for HCoV-229E and HCoV-NL63 were similar (suggesting that vaccination did not affect these baseline values). Among vaccinated individuals without prior COVID-19 infection, SARS-COV-2 anti-spike IgG demonstrated a weak positive relationship between both HCoV-229E (r = 0.11) and HCoV-NL63 (r = 0.12). From the adjusted log-log multiple regression model, higher HCoV-229E and HCoV-NL63 anti-spike IgG antibodies were associated with increased SARS-COV-2 anti-spike IgG antibodies. Vaccination appears to result in measurable increases in HCoV-HKU1, and HCoV-OC43 IgG levels. Anti-HCoV-229E and HCoV-NL63 antibodies were unaffected by vaccination, and higher levels were associated with significantly higher COVID-19 vaccine-induced SARS-COV-2 antibodies.
Serum proteomic networks associate with pre-clinical rheumatoid arthritis autoantibodies and longitudinal outcomes
Authors: O’Neil Liam J. , Meng Xiaobo , Mcfadyen Caitlin , Fritzler Marvin J. , El-Gabalawy Hani S.
Published: September 2022

Objectives

The development of autoantibody directed towards citrullinated proteins (ACPA) are predictive of RA in at-risk individuals. The biological events that underpin loss of immune tolerance and progression into inflammatory arthritis are not known. We sought to identify serum proteomic alterations that drive autoantibody formation, persistence and progression into inflammatory arthritis in a cohort of first-degree relatives (FDR) of RA patients.

Methods

We studied baseline serum samples from a cohort of Indigenous FDR (n = 147) and quantified serum proteins using a 48-plex platform. Longitudinal outcomes were defined on the basis of ACPA status and progression into inflammatory arthritis (IA). K-means clustering, differential expression, and principal components analyze group differences. A co-expression module analysis was used to identify enriched networks. Random forest was used to classify ACPA positive samples, while network analysis was used to understand underlying biological processes based on protein expression.

Results

We defined 6 proteomic clusters, with enrichment of ACPA positive samples in one of the clusters. 23 of 24 differentially expressed proteins in ACPA positive samples were upregulated. A co-expression network was enriched in ACPA positive sera and individuals who progressed into IA. Random Forest achieved an area under the curve of 0.767 to classify ACPA positive sera in a test dataset. Network analysis revealed upregulation of JAK-STAT signalling as being activated in those at highest risk to develop future IA.

Conclusions

The serum proteome provides a rich dataset to understand biological processes in ACPA seropositive individuals. A combination of serum biomarkers, including ACPA, may predict future arthritis onset in at-risk individuals.
Combined – whole blood and skin fibroblasts- transcriptomic analysis in Psoriatic Arthritis reveals molecular signatures of activity, resistance and early response to treatment
Authors: Grivas Alexandros , Grigoriou Maria , Malissovas Nikos , Sentis George , Filia Anastasia , Flouda Sofia , Katsimpri Pelagia , Verginis Panayotis , Boumpas Dimitrios T.
Published: September 2022

Background

An interplay between immune cells and resident skin and joint stromal cells is implicated in psoriatic arthritis (PsA), yet the mechanisms remain elusive with a paucity of molecular biomarkers for activity and response. Combined transcriptomic and immunophenotypic analysis of whole blood and skin fibroblasts could provide further insights.

Methods

Whole blood RNA-seq was performed longitudinally in 30 subjects with PsA at the beginning, one and six months after treatment, with response defined at six months. As control groups, 10 healthy individuals and 10 subjects with rheumatoid arthritis (RA) were recruited combined with public datasets from patients with psoriasis (PsO) and systemic lupus erythematous (SLE). Differential expression analysis and weighted gene co-expression network analysis were performed to identify gene expression signatures, while deconvolution and flow cytometry to characterize the peripheral blood immune cell profile. In a subset of affected and healthy individuals, RNA-seq of skin fibroblasts was performed and subjected to CellChat analysis to identify the blood-skin fibroblast interaction network.

Results

PsA demonstrated a distinct “activity” gene signature in the peripheral blood dominated by TNF- and IFN-driven inflammation, deregulated cholesterol and fatty acid metabolism and expansion of pro-inflammatory non-classical monocytes. Comparison with the blood transcriptome of RA, PsO, and SLE revealed a “PsA-specific signature” enriched in extracellular matrix remodeling. This was further supported by the skin fibroblast gene expression profile, displaying an activated, proliferating phenotype, and by skin-blood interactome analysis revealing interactions with circulating immune cells through WNT, PDGF and immune-related semaphorins. Of note, resistance to treatment was associated with upregulation of genes involved in TGFβ signaling and angiogenesis and persistent increase of non-classical monocytes. Differentially expressed genes related to platelet activation and hippo signaling discriminated responders and non-responders as early as one month after treatment initiation.

Conclusion

Transcriptome analysis of peripheral blood and skin fibroblasts in PsA reveals a distinct disease activity signature and supports the involvement of skin fibroblasts through their activation and interaction with circulating immune cells. Aberrant TGFβ signaling and persistently increased non-classical monocytes characterize treatment-resistant PsA, with pro-inflammatory pathways related to platelet activation and Hippo signaling predicting early response to treatment.
IL-2 and IL-15 drive intrathymic development of distinct periphery-seeding CD4+Foxp3+ regulatory T lymphocytes
Authors: Apert Cécile , Galindo-Albarrán Ariel O. , Castan Sarah , Detraves Claire , Michaud Héloise , McJannett Nicola , Haegeman Bart , Fillatreau Simon , Malissen Bernard , Holländer Georg , Žuklys Saulius , Santamaria Jérémy C. , Joffre Olivier P. , Romagnoli Paola , van Meerwijk Joost P. M.
Published: September 2022

Development of Foxp3-expressing regulatory T-lymphocytes (Treg) in the thymus is controlled by signals delivered in T-cell precursors via the TCR, co-stimulatory receptors, and cytokine receptors. In absence of IL-2, IL-15 or their receptors, fewer Treg apparently develop in the thymus. However, it was recently shown that a substantial part of thymic Treg are cells that had recirculated from the periphery back to the thymus, troubling interpretation of these results. We therefore reassessed the involvement of IL-2 and IL-15 in the development of Treg, taking into account Treg-recirculation. At the age of three weeks, when in wt and IL-15-deficient (but not in IL-2-deficient) mice substantial amounts of recirculating Treg are present in the thymus, we found similarly reduced proportions of newly developed Treg in absence of IL-2 or IL-15, and in absence of both cytokines even less Treg developed. In neonates, when practically no recirculating Treg were found in the thymus, the absence of IL-2 led to substantially more reduced Treg-development than deficiency in IL-15. IL-2 but not IL-15 modulated the CD25, GITR, OX40, and CD73-phenotypes of the thymus-egress-competent and periphery-seeding Treg-population. Interestingly, IL-2 and IL-15 also modulated the TCR-repertoire expressed by developing Treg. Upon transfer into Treg-less Foxp3sf mice, newly developed Treg from IL-2- (and to a much lesser extent IL-15-) deficient mice suppressed immunopathology less efficiently than wt Treg. Taken together, our results firmly establish important non-redundant quantitative and qualitative roles for IL-2 and, to a lesser extent, IL-15 in intrathymic Treg-development.
Case report: Documentation of cutaneous only pemphigus vulgaris without history of mucosal lesions in North America
Authors: Baker John , Seiffert-Sinha Kristina , Sinha Animesh A.
Published: September 2022

Background

Pemphigus is a group of autoimmune blistering diseases including Pemphigus vulgaris (PV) and Pemphigus foliaceus (PF). These conditions exhibit lesions with mucosal or mucocutaneous (PV) or cutaneous (PF) morphology, as framed by the Desmoglein Compensation Hypothesis (DCH). However, some PV patients present with solely cutaneous disease (cPV), and growing evidence suggests the existence of a cPV subtype without any history of mucosal erosions/blisters (cPVwohm), neither of which are predicted by the DCH.

Methods

Participants were recruited from several outpatient clinical settings and patient support group meetings throughout the US. On intake, subjects provided blood samples and completed questionnaires regarding their disease status.

Results

We report three cases of clinically and histologically confirmed cPV without history of mucosal lesions (cPVwohm). Of these patients, two do not carry the most common PV associated HLA alleles, DRB1*0402 or DQB1*0503. The same two patients also tested negative for the primary PV associated autoantibodies, anti-desmoglein 3 and anti-desmoglein 1, while in active disease status.

Conclusion

We confirm the first documented individual cases of cPVwohm in North America, supporting the existence of PV patients that develop cutaneous disease without a history of mucosal lesions, challenging the fidelity of the DCH. Two of the 3 patients reported did not type for the common PV-associated HLA genes or display anti-desmoglein autoantibodies while in active disease, suggesting cPV patients may develop Pemphigus via genetic and immune mechanisms that differ from typical mucosal or mucocutaneous PV.
Annexin A2 regulates Mycoplasma bovis adhesion and invasion to embryo bovine lung cells affecting molecular expression essential to inflammatory response
Authors: Zhang Hui , Lu Doukun , Zhang Yiqiu , Zhao Gang , Raheem Abdul , Chen Yingyu , Chen Xi , Hu Changmin , Chen Huanchun , Yang Liguo , Guo Aizhen
Published: September 2022

Mycoplasma bovis (M. bovis) is an important pathogen of the bovine respiratory disease complex, invading lower respiratory tracts and causing severe pneumonia. However, its molecular mechanism largely remains unknown. Host annexin A2 (ANXA2) is a calcium-dependent phospholipid-binding protein. The current study sought to determine whether ANXA2 could mediate M. bovis adhesion and invasion thereby affecting its induction of inflammatory response. ANXA2 expression was upregulated in M. bovis-infected bovine lung epithelial cells (EBL), and blocking ANXA2 with an anti-ANXA2 antibody reduced M. bovis adhesion to EBL. Compared with uninfected cells, more ANXA2 was translocated from the cytoplasm to the cell surface after M. bovis infection. Furthermore, RNA interference knockdown of ANXA2 expression in EBL cells resulted in a significant decrease in M. bovis invasion and F-actin polymerization. Next, the transcriptomic study of M. bovis-infected EBL cells with and without ANXA2 knockdown were performed. The data exhibited that ANXA2 knockdown EBL cells had 2487 differentially expressed genes (DEGs), with 1175 upregulated and 1312 downregulated compared to control. According to GO and KEGG analyses, 50 genes potentially linked to inflammatory responses, 23 involved in extracellular matrix (ECM) receptor interaction, and 48 associated with PI3K-AKT signal pathways were upregulated, while 38 mRNA binding genes, 16 mRNA 3′-UTR binding genes, and 34 RNA transport genes were downregulated. Furthermore, 19 genes with various change-folds were selected for qPCR verification, and the results agreed with the RNA-seq findings. Above all, the transcription of two chemokines (IL-8 and CXCL5) and a key bovine β-defensin TAP in IL-17 signaling pathway were significantly increased in ANXA2 knockdown cells. Moreover, ANXA2 knockdown or knockout could increase NF-κB and MAPK phosphorylation activity in response to M. bovis infection. Additionally, ANXA2 knockdown also significantly decreased the CD44 transcripts via exon V3 and V7 skipping after M. bovis infection. We concluded that M. bovis borrowed host ANXA2 to mediate its adhesion and invasion thereby negatively regulating molecular expression essential to IL-17 signal pathway. Furthermore, CD44 V3 and V7 isoforms might contribute to this ANXA2 meditated processes in M. bovis infected EBL cells. These findings revealed a new understanding of pathogenesis for M. bovis infection.
Case Report: Association between cyclic neutropenia and SRP54 deficiency
Authors: Erdős Melinda , Boyarchuk Oksana , Maródi László
Published: September 2022

Autosomal dominant mutations in the signal recognition particle (SRP) 54 gene were recently described in patients with severe congenital neutropenia (SCN). SRP54 deficiency cause a chronic and profound neutropenia with maturation arrest at the promyelocyte stage, occurring in the first months of life. Nearly all reported patients with SRP54 mutations had neutropenia without a cyclic pattern and showed a poor or no response to granulocyte colony-stimulating factor (G-CSF) therapy. We report here an 11-year-old female patient with cyclic neutropenia and recurrent heterozygous p.T117del (c.349_351del) in-frame deletion mutation in SRP54, who showed remarkable therapeutic response to G-CSF treatment. The diagnosis of cyclic pattern of neutropenia was established by acceptable standards. ELANE gene mutation was excluded by using various genetic approaches. The patient described here also had dolichocolon which has not been described before in association with SCN.
The importance of booster vaccination in the context of Omicron wave
Authors: Wei Zichun , He Jiarui , Wang Conghui , Bao Jiaqi , Leng Taiyang , Chen Fei
Published: September 2022

Omicron (B.1.1.529) was first detected in a sample collected in Botswana on November 11, 2021, and has rapidly replaced Delta as the dominant global variant given the robust transmissibility. Moreover, it displays a lower virulence than other variants. However, the pathogenicity of Omicron appears to be underestimated in view of the increasing levels of herd immunity through natural infection or vaccination. Additionally, the volume of hospitalizations and deaths increase in proportion to the number of cases due to the high transmissibility of Omicron. Therefore, vaccination remains an important public health priority. Notably, a series of important mutations in the Omicron spike protein, especially in the receptor-binding domain and N-terminal domain, appears to be associated with immune escape capacity, reducing the willingness of people to receive vaccines. Herein, we provide an in-depth discussion to assess the effectiveness of the second and third vaccination against Omicron variant. On the one hand, the two-dose vaccination program adopted by many countries is insufficient to prevent Omicron infection given the mutations correlated with immune escape and the decline in vaccine efficacy over time. On the other hand, booster dose significantly increases the protective efficacy against Omicron infection. Most importantly, heterologous third dose vaccination induces a more robust immune response than homologous booster dose. Therefore, under the special background of this pandemic, there is an urgent need to accelerate the third dose of vaccination, especially providing better booster vaccination strategies, to combat emerging Omicron variant.
Comparable bidirectional neutrophil immune dysregulation between Kawasaki disease and severe COVID-19
Authors: Chen Kuang-Den , Huang Ying-Hsien , Wu Wei-Sheng , Chang Ling-Sai , Chu Chiao-Lun , Kuo Ho-Chang
Published: September 2022

Kawasaki disease (KD), a multisystem inflammatory syndrome that occurs in children, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) may share some overlapping mechanisms. The purpose of this study was to analyze the differences in single-cell RNA sequencing between KD and COVID-19. We performed single-cell RNA sequencing in KD patients (within 24 hours before IVIG treatment) and age-matched fever controls. The single-cell RNA sequencing data of COVID-19, influenza, and health controls were downloaded from the Sequence Read Archive (GSE149689/PRJNA629752). In total, 22 single-cell RNA sequencing data with 102,355 nuclei were enrolled in this study. After performing hierarchical and functional clustering analyses, two enriched gene clusters demonstrated similar patterns in severe COVID-19 and KD, heightened neutrophil activation, and decreased MHC class II expression. Furthermore, comparable dysregulation of neutrophilic granulopoiesis representing two pronounced hyperinflammatory states was demonstrated, which play a critical role in the overactivated and defective aging program of granulocytes, in patients with KD as well as those with severe COVID-19. In conclusion, both neutrophil activation and MHC class II reduction play a crucial role and thus may provide potential treatment targets for KD and severe COVID-19.
Issues on the inclusion of Puntius denisonii (Day), a freshwater ornamental fish of global value, as Schedule-I species under the Wild Life (Protection) Amendment Act, 2021 of India
Authors: Jain Atul Kumar , Mercy T. V. A. , Jain Abhinika
Published: September 2022

Puntius denisoniiis popularly known as Miss Kerala in India or Denison barb or Red line torpedo barb in the global ornamental fish trade. The species is endemic to fast-flowing rivers and streams of the Western Ghats of India. The species was not very popular earlier in aquatic trade but has been in great demand in global aquarium trade since it was exhibited at AQARAMA 1997 in Singapore and ranked third under the new species category. The export of the species from India started in 1996–1997, which increased progressively and constituted about 60%–65% of a total of 1.44 million US$ worth of ornamental fish exported from India in 2007–2008. Thereafter, it started declining and presently became negligible. It was attributed to depleting stocks ofP. denisoniiin rivers and streams of Western Ghats. The species was recommended to be listed as endangered on the IUCN red list in a CAMP workshop held at NBFGR, Lucknow, India in September 1997, owing to habitat degradation and the declining number of mature individuals in the wild. It was categorized as Vulnerable in 2009 and Endangered in 2015 under the IUCN red list. The Department of Fisheries, Government of Kerala has restricted the collection of smaller size fish from natural water bodies since 2008 to revive wild stocks. The Ministry of Environment, Forest and Climate Change, Government of India has now proposed to includeP. denisoniialong with two other freshwater fish species,Semiplotus semiplotus(Assamese kingfish) andOsteobrama belangeri(Manipur osteobrama), as Schedule-I species under the Wild Life (Protection) Amendment Act, 2021 of India. The species listed under this Schedule are prohibited to be hunted throughout the country. The captive breeding technology ofP. denisoniihas already been developed in the country more than a decade back, and fish is being produced commercially at several farms presently including hatcheries of the Kerala Government. The species is also being cultured and produced on a commercial scale by many ornamental fish farmers of Indonesia and supplied to the global ornamental fish trade at cheaper rates, and more color strains. The major factors that are responsible for the depletion of the stocks ofP. denisoniiand the overall fish biodiversity of Western Ghat regions are discussed in detail. The conflicts and repercussions that will arise because of the inclusion of Denison Barb or any other freshwater fish as Schedule-I species under the Wild Life (Protection) Amendment Act, 2021 of India are also discussed.
Hybridization in wire arc additive manufacturing
Authors: Kapil Sajan , Rajput Atul Singh , Sarma Ritam
Published: September 2022

Wire Arc Additive Manufacturing (WAAM) can produce a near-net shape of an object within a short period due to its capability of high deposition rate compared with other metal Additive Manufacturing (AM) processes. The recent developments in the WAAM have increased its efficiency and cost-effectiveness in producing viable products. However, poor surface quality, porosities, residual stresses, distortions, and anisotropic mechanical properties are a few inherent challenges still associated with the WAAM, which necessitates the hybridization of this process. Hybrid-WAAM is a synergic integration of one or more deposition processes, manufacturing processes, layering strategies, raw stock materials, and machine tool kinematics that are fully coupled and affect part quality, functionality, and process performance. This paper comprehensively reviews different levels of hybridization in the WAAM to eliminate its associated challenges. These levels of hybridizations are classified into five categories: hybrid-deposition processes, hybrid-manufacturing processes, hybrid-layering strategies, hybrid-machine tools, and hybrid-raw stock. Furthermore, these levels of hybridization are mapped to eliminate the associated defects/challenges in the WAAM, which will help the readers select an appropriate level of hybridization.
Multifrequency bioimpedance by spectroscopy vs. routine methods in the management of hydration status in peritoneal dialysis patients: A randomized control trial
Authors: Costa Fabiana Lourenço , Reis Nayrana Soares do Carmo , Reis Fabricio Moreira , Oliveira Rogério Carvalho de , Zanati Bazan Silméia Garcia , Canedo da Silva Maryanne Zilli , Martin Luis Cuadrado , Barretti Pasqual
Published: September 2022

Background

Overhydration (OH) is common in peritoneal dialysis (PD) and increases the cardiovascular risk. Multifrequency bioimpedance spectroscopy (BIS) has been proposed to estimate the hydration in dialysis. Our objective was to evaluate if BIS is superior than control based on clinical assessment plus single-frequency bioimpedance (SF-BIA) on the fluid control and intermediate cardiovascular outcomes.

Methods

Randomized controlled study in adult PD patients, with a 9-month follow-up, allocated into two groups: control and BIS. Data were collected from medical records. SF-BIA and BIS, laboratory exams, ambulatory blood pressure monitoring, echocardiography (ECHO), and pulse wave velocity (PWV) were evaluated. The BIS data were available to the medical team only in BIS group.

Results

34 patients completed the study, 17 in each group. At the endpoint the BIS group had a significant (p < 0.05) greater proportion of patients with OH/extracellular water (OH/ECW%) ≤ 15% than the control (94.1% vs. 52.9%), and a lower OH mean (2.1 ± 1.6 vs. 0.9 ± 1.1 L). The control group has a significant increase in the tumor necrosis factor alpha median concentration from baseline to six [11.9 (6.0–24.1) vs. 44.7 (9.4–70.6) pg/ml] and 9 months [11.9 (6.0–24.1) vs. 39.4 (27.9–62.6) pg/ml], and in the N-terminal fragment of pro-B-type natriuretic peptide median [239 (171.5–360.5) vs. 356 (219–1,555) pg/ml]. For cardiovascular parameters, BIS group presented a significant reduction in radial PWV [7.7 (6.9–9.2) vs. 6.5 (5.5–8.4) m/s] at 9 month, while in the control presented a significant increase in mean central systolic blood pressure (BP) (106.8 ± 11.2 vs. 117.6 ± 16.5 mmHg) and in central diastolic BP (90.4 ± 9.8 vs. 103.3 ± 12.5 mmHg) at 9 months. The left ventricular mass (LVM)/body surface presented a significant reduction in the control (109.6 ± 30.8 vs. 101.2 ± 28.9 g/m2) and BIS group (107.7 ± 24.9 vs. 96.1 ± 27.0 g/m2) at 9 months.

Conclusion

The results suggest BIS is superior than the clinical evaluation plus SF-BIA for the fluid control of PD patients.

Clinical trial registration

[https://www.ClinicalTrials.gov], identifier [RBR-10k8j3bx].