bluuebunny/crossref_metadata_2025 huggingface dataset:
Does withdrawal from/remaining in an aggressor country affect companies’ ESG ratings? Case study of the Russia-Ukraine war
Authors: Dincă Marius Sorin , Vezeteu Cosmin-Dănuț , Dincă Dragoș
Published: July 2023

As we mark one year since the start of the Russia-Ukraine war, countries and companies alike continue to adapt to this unprecedented disruption in the global economy and the subsequent uncertainty. One aspect that has not been thoroughly addressed from this conflict is its effect on companies’ ESG ratings and how the decision to remain or withdraw from Russia influences these ratings. To study this, a panel regression methodology on ESG data was applied on a significant number of companies before and after the start of the conflict. According to the results obtained, it would seem that insofar neither the overall ESG scores, nor the Social Scores are influenced by companies’ decisions to leave or to stay in Russia after 24-th of February 2022. We consider that these are not final outcomes and it will require further investigations and methodology improvements. The paper provides insights for ESG ratings providers, regulators and asset managers on the effects of companies’ decision to withdraw from/remain in an invading country on ESG ratings.
Advances in epigenetic research of adolescent idiopathic scoliosis and congenital scoliosis
Authors: Sun Duan , Ding Zihao , Hai Yong , Cheng Yunzhong
Published: July 2023

Scoliosis is a three-dimensional structural deformity of the spine; more than 80% of scoliosis has no specific pathogenesis but is understood to be closely related to genetic, hormonal, and environmental factors. In recent years, the epigenetic alterations observed in scoliosis have been analyzed in numerous studies to determine the pathogenesis and progression of this condition, however, there is currently no comprehensive review of the epigenetic factors to date. We searched PubMed, Embase, and Web of Science databases for relative studies without language and date restrictions in March 2023. Twenty-five studies were included in this review and analyzed from the four main aspects of epigenetic alteration: DNA methylation, non-coding RNAs, histone modifications, and chromatin remodeling. The relationship between DNA methylation, non-coding RNAs, and scoliosis was considerably reported in the literature, and the corresponding related signaling pathways and novel biomarkers observed in scoliosis provide insights into innovative prevention and treatment strategies. However, the role of histone modifications is rarely reported in scoliosis, and few studies have investigated the relationship between scoliosis and chromatin remodeling. Therefore, these related fields need to be further explored to elucidate the overall effects of epigenetics in scoliosis.
Analysis of lactate metabolism-related genes and their association with immune infiltration in septic shock via bioinformatics method
Authors: Jiang Huimin , Ren Yun , Yu Jiale , Hu Sheng , Zhang Jihui
Published: July 2023

Background: Lactate, as an essential clinical evaluation index of septic shock, is crucial in the incidence and progression of septic shock. This study aims to investigate the differential expression, regulatory relationship, clinical diagnostic efficacy, and immune infiltration of lactate metabolism-related genes (LMGs) in septic shock.

Methods: Two sepsis shock datasets (GSE26440 and GSE131761) were screened from the GEO database, and the common differentially expressed genes (DEGs) of the two datasets were screened out. LMGs were selected from the GeneCards database, and lactate metabolism-related DEGs (LMDEGs) were determined by integrating DEGs and LMGs. Protein-protein interaction networks, mRNA-miRNA, mRNA-RBP, and mRNA-TF interaction networks were constructed using STRING, miRDB, ENCORI, and CHIPBase databases, respectively. Receiver operating characteristic (ROC) curves were constructed for each of the LMDEGs to evaluate the diagnostic efficacy of the expression changes in relation to septic shock. Finally, immune infiltration analysis was performed using ssGSEA and CIBERSORT.

Results: This study identified 10 LMDEGs, including LDHB, STAT3, LDHA, GSR, FOXM1, PDP1, GCDH, GCKR, ABCC1, and CDKN3. Enrichment analysis revealed that DEGs were significantly enriched in pathways such as pyruvate metabolism, hypoxia pathway, and immune-inflammatory pathways. PPI networks based on LMDEGs, as well as 148 pairs of mRNA-miRNA interactions, 243 pairs of mRNA-RBP interactions, and 119 pairs of mRNA-TF interactions were established. ROC curves of eight LMDEGs (LDHA, GSR, STAT3, CDKN3, FOXM1, GCKR, PDP1, and LDHB) with consistent expression patterns in two datasets had an area under the curve (AUC) ranging from 0.662 to 0.889. The results of ssGSEA and CIBERSORT both showed significant differences in the infiltration of various immune cells, including CD8 T cells, T regulatory cells, and natural killer cells, and LMDEGs such as STAT3, LDHB, LDHA, PDP1, GSR, FOXM1, and CDKN3 were significantly associated with various immune cells.

Conclusion: The LMDEGs are significantly associated with the immune-inflammatory response in septic shock and have a certain diagnostic accuracy for septic shock.
Fc receptors act as innate immune receptors during infection?
Authors: Laassili Chaimaa , Ben El Hend Fatiha , Benzidane Riad , Oumeslakht Loubna , Aziz Abdel-Ilah , El Fatimy Rachid , Bensussan Armand , Ben Mkaddem Sanae
Published: July 2023

Innate immunity constitutes the first nonspecific immunological line of defense against infection. In this response, a variety of mechanisms are activated: the complement system, phagocytosis, and the inflammatory response. Then, adaptive immunity is activated. Major opsonization mediators during infections are immunoglobulins (Igs), the function of which is mediated through Fc receptors (FcRs). However, in addition to their role in adaptive immunity, FcRs have been shown to play a role in innate immunity by interacting directly with bacteria in the absence of their natural ligands (Igs). Additionally, it has been hypothesized that during the early phase of bacterial infection, FcRs play a protective role via innate immune functions mediated through direct recognition of bacteria, and as the infection progresses to later phases, FcRs exhibit their established function as receptors in adaptive immunity. This review provides detailed insight into the potential role of FcRs as innate immune mediators of the host defense against bacterial infection independent of opsonins.
Immunomodulatory potential of mesenchymal stromal cell-derived extracellular vesicles in chondrocyte inflammation
Authors: Ossendorff Robert , Grad Sibylle , Tertel Tobias , Wirtz Dieter C. , Giebel Bernd , Börger Verena , Schildberg Frank A.
Published: July 2023

Introduction

Osteoarthritis (OA) affects a large percentage of the population worldwide. Current surgical and nonsurgical concepts for treating OA only result in symptom-modifying effects. However, there is no disease-modifying therapy available. Extracellular vesicles released by mesenchymal stem/stromal cells (MSC-EV) are promising agents to positively influence joint homeostasis in the osteoarthritic surroundings. This pilot study aimed to investigate the effect of characterized MSC-EVs on chondrogenesis in a 3D chondrocyte inflammation model with the pro-inflammatory cytokine TNFα.

Methods

Bovine articular chondrocytes were expanded and transferred into pellet culture at passage 3. TNFα, human MSC-EV preparations (MSC-EV batches 41.5-EVi1 and 84-EVi), EVs from human platelet lysate (hPL4-EV), or the combination of TNFα and EVs were supplemented. To assess the effect of MSC-EVs in the chondrocyte inflammation model after 14 days, DNA, glycosaminoglycan (GAG), total collagen, IL-6, and NO release were quantified, and gene expression of anabolic (COL-II, aggrecan, COMP, and PRG-4), catabolic (MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5), dedifferentiation (COL-I), hypertrophy (COL-X, VEGF), and inflammatory (IL-8) markers were analyzed; histological evaluation was performed using safranin O/Fast Green staining and immunohistochemistry of COL I and II. For statistical evaluation, nonparametric tests were chosen with a significance level of p < 0.05.

Results

TNFα supplementation resulted in catabolic stimulation with increased levels of NO and IL-6, upregulation of catabolic gene expression, and downregulation of anabolic markers. These findings were supported by a decrease in matrix differentiation (COL-II). Supplementation of EVs resulted in an upregulation of the chondrogenic marker PRG-4. All MSC-EV preparations significantly increased GAG retention per pellet. In contrast, catabolic markers and IL-8 expression were upregulated by 41.5-EVi1. Regarding protein levels, IL-6 and NO release were increased by 41.5-EVi1. Histologic and immunohistochemical evaluations indicated a higher differentiation potential of chondrocytes treated with 84-EVi.

Discussion

MSC-EVs can positively influence chondrocyte matrix production in pro-inflammatory surroundings, but can also stimulate inflammation. In this study MSC-EV 41.5-EVi1 supplementation increased chondrocyte inflammation, whereas MSC-84-EVi supplementation resulted a higher chondrogenic potential of chondrocytes in 3D pellet culture. In summary, the selected MSC-EVs exhibited promising chondrogenic effects indicating their significant potential for the treatment of OA; however, the functional heterogeneity in MSC-EV preparations has to be solved.
The podocyte: glomerular sentinel at the crossroads of innate and adaptive immunity
Authors: Burke George W. , Mitrofanova Alla , Fontanella Antonio , Ciancio Gaetano , Roth David , Ruiz Phil , Abitbol Carolyn , Chandar Jayanthi , Merscher Sandra , Fornoni Alessia
Published: July 2023

Focal segmental glomerulosclerosis (FSGS) is a common glomerular disorder that manifests clinically with the nephrotic syndrome and has a propensity to recur following kidney transplantation. The pathophysiology and therapies available to treat FSGS currently remain elusive. Since the podocyte appears to be the target of apparent circulating factor(s) that lead to recurrence of proteinuria following kidney transplantation, this article is focused on the podocyte. In the context of kidney transplantation, the performance of pre- and post-reperfusion biopsies, and the establishment of in vitro podocyte liquid biopsies/assays allow for the development of clinically relevant studies of podocyte biology. This has given insight into new pathways, involving novel targets in innate and adaptive immunity, such as SMPDL3b, cGAS-STING, and B7-1. Elegant experimental studies suggest that the successful clinical use of rituximab and abatacept, two immunomodulating agents, in our case series, may be due to direct effects on the podocyte, in addition to, or perhaps distinct from their immunosuppressive functions. Thus, tissue biomarker-directed therapy may provide a rational approach to validate the mechanism of disease and allow for the development of new therapeutics for FSGS. This report highlights recent progress in the field and emphasizes the importance of kidney transplantation and recurrent FSGS (rFSGS) as a platform for the study of primary FSGS.
Transcriptomic profile of TNFhigh MAIT cells is linked to B cell response following SARS-CoV-2 vaccination
Authors: Marzano Paolo , Balin Simone , Terzoli Sara , Della Bella Silvia , Cazzetta Valentina , Piazza Rocco , Sandrock Inga , Ravens Sarina , Tan Likai , Prinz Immo , Calcaterra Francesca , Di Vito Clara , Cancellara Assunta , Calvi Michela , Carletti Anna , Franzese Sara , Frigo Alessandro , Darwish Ahmed , Voza Antonio , Mikulak Joanna , Mavilio Domenico
Published: July 2023

Introduction

Higher frequencies of mucosal-associated invariant T (MAIT) cells were associated with an increased adaptive response to mRNA BNT162b2 SARS-CoV-2 vaccine, however, the mechanistic insights into this relationship are unknown. In the present study, we hypothesized that the TNF response of MAIT cells supports B cell activation following SARS-CoV-2 immunization.

Methods

To investigate the effects of repeated SARS-CoV-2 vaccinations on the peripheral blood mononuclear cells (PBMCs), we performed a longitudinal single cell (sc)RNA-seq and scTCR-seq analysis of SARS-CoV-2 vaccinated healthy adults with two doses of the Pfizer-BioNTech BNT162b2 mRNA vaccine. Collection of PBMCs was performed 1 day before, 3 and 17 days after prime vaccination, and 3 days and 3 months following vaccine boost. Based on scRNA/TCR-seq data related to regulatory signals induced by the vaccine, we used computational approaches for the functional pathway enrichment analysis (Reactome), dynamics of the effector cell-polarization (RNA Velocity and CellRank), and cell-cell communication (NicheNet).

Results

We identified MAIT cells as an important source of TNF across circulating lymphocytes in response to repeated SARS-CoV-2 BNT162b2 vaccination. The TNFhigh signature of MAIT cells was induced by the second administration of the vaccine. Notably, the increased TNF expression was associated with MAIT cell proliferation and efficient anti-SARS-CoV-2 antibody production. Finally, by decoding the ligand-receptor interactions and incorporating intracellular signaling, we predicted TNFhigh MAIT cell interplay with different B cell subsets. In specific, predicted TNF-mediated activation was selectively directed to conventional switched memory B cells, which are deputed to high-affinity long-term memory.

Discussion

Overall, our results indicate that SARS-CoV-2 BNT162b2 vaccination influences MAIT cell frequencies and their transcriptional effector profile with the potential to promote B cell activation. This research also provides a blueprint for the promising use of MAIT cells as cellular adjuvants in mRNA-based vaccines.
Multi-phasic gene profiling using candidate gene approach predict the capacity of specific antibody production and maintenance following COVID-19 vaccination in Japanese population
Authors: Takemoto Yuki , Tanimine Naoki , Yoshinaka Hisaaki , Tanaka Yuka , Takafuta Toshiro , Sugiyama Aya , Tanaka Junko , Ohdan Hideki
Published: July 2023

Background

Vaccination against severe acute respiratory syndrome coronavirus type 2 is highly effective in preventing infection and reducing the severity of coronavirus disease (COVID-19). However, acquired humoral immunity wanes within six months. Focusing on the different tempo of acquisition and attenuation of specific antibody titers in individuals, we investigated the impact of genetic polymorphisms on antibody production after COVID-19 vaccination.

Methods

In total 236 healthcare workers from a Japanese municipal hospital, who received two doses of the vaccine were recruited. We employed a candidate gene approach to identify the target genetic polymorphisms affecting antibody production after vaccination. DNA samples from the study populations were genotyped for 33 polymorphisms in 15 distinct candidate genes encoding proteins involved in antigen-presenting cell activation, T cell activation, T-B interaction, and B cell survival. We measured total anti-SARS-Cov2 spike IgG antibody titers and analyzed the association with genetic polymorphisms at several time points after vaccination using an unbiased statistical method, and stepwise logistic regression following multivariate regression.

Results

Significant associations were observed between seven SNPs in NLRP3, OAS1, IL12B, CTLA4, and IL4, and antibody titers at 3 weeks after the first vaccination as an initial response. Six SNPs in NLRP3, TNF, OAS1, IL12B, and CTLA4 were associated with high responders with serum antibody titer > 4000 BAU/ml as boosting effect at 3 weeks after the second vaccination. Analysis of long-term maintenance showed the significance of the three SNPs in IL12B, IL7R, and MIF for the maintenance of antibody titers and that in BAFF for attenuation of neutralizing antibodies. Finally, we proposed a predictive model composed of gene profiles to identify the individuals with rapid antibody attenuation by receiver operating characteristic (ROC) analysis (area under the curve (AUC)= 0.76, sensitivity = 82.5%, specificity=67.8%).

Conclusions

The candidate gene approach successfully showed shifting responsible gene profiles and initial and boosting effect mainly related to the priming phase into antibody maintenance including B cell survival, which traces the phase of immune reactions. These gene profiles provide valuable information for further investigation of humoral immunity against COVID-19 and for building a strategy for personalized vaccine schedules.
Cellular immune response of SARS-CoV-2 vaccination in kidney transplant recipients: a systematic review and meta-analysis
Authors: Udomkarnjananun Suwasin , Gatechompol Sivaporn , Leelahavanichkul Asada , Kerr Stephen J.
Published: July 2023

Background

Evidence has demonstrated inferior humoral immune responses after SARS-CoV-2 vaccination in kidney transplant recipients compared to the general population. However, data on cellular immune responses in this population have not been established.

Methods

We searched the MEDLINE, Scopus, and Cochrane databases and included studies reporting cellular immune response rates in kidney transplant recipients after receiving SARS-CoV-2 vaccines. Studies that reported factors associated with cellular immune responders or non-responders were also included (PROSPERO: CRD42022375544).

Results

From a total of 1,494 articles searched, 53 articles were included in the meta-analysis. In all, 21 studies assessed cellular immune response by interferon-γ enzyme-linked immunosorbent spot (IFN-γ ELISPOT), 22 studies used interferon-γ release assay (IGRA), and 10 studies used flow cytometric analysis. The pooled response rate after two doses (standard regimen) and three doses of vaccination was 47.5% (95%CI 38.4-56.7%) and 69.1% (95%CI 56.3-80.6%) from IFN-γ ELISPOT, 25.8% (95%CI 19.7-32.4%) and 14.7% (95%CI 8.5-22.2%) from IGRA, and 73.7% (95%CI 55.2-88.8%) and 86.5% (95%CI 75.3-94.9%) from flow cytometry, respectively. Recipients with seroconversion were associated with a higher chance of having cellular immune response (OR 2.58; 95%CI 1.89-3.54). Cellular immune response in kidney transplant recipients was lower than in dialysis patients (OR 0.24; 95%CI 0.16-0.34) and the general population (OR 0.10; 95%CI 0.07-0.14). Age and immunosuppressants containing tacrolimus or corticosteroid were associated with inferior cellular immune response.

Conclusion

Cellular immune response after SARS-CoV-2 vaccination in kidney transplant recipients was lower than in dialysis patients and the general population. Age, tacrolimus, and corticosteroid were associated with poor response. Cellular immune response should also be prioritized in vaccination studies.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42022375544.
Metabolic prioritization of fish in hypoxic waters: an integrative modeling approach
Authors: Duskey Elizabeth
Published: July 2023

Marine hypoxia has had major consequences for both economically and ecologically critical fish species around the world. As hypoxic regions continue to grow in severity and extent, we must deepen our understanding of mechanisms driving population and community responses to major stressors. It has been shown that food availability and habitat use are the most critical components of impacts on individual fish leading to observed outcomes at higher levels of organization. However, differences within and among species in partitioning available energy for metabolic demands – or metabolic prioritization – in response to stressors are often ignored. Here, I use both a multispecies size spectrum model and a meta-analysis to explore evidence in favor of metabolic prioritization in a community of commercially important fish species in the Baltic Sea. Modeling results suggest that metabolic prioritization is an important component of the individual response to hypoxia, that it interacts with other components to produce realistic community dynamics, and that different species may prioritize differently. It is thus suggested that declines in feeding activity, assimilation efficiency, and successful reproduction – in addition to low food availability and changing habitat use – are all important drivers of the community response to hypoxia. Meta-analysis results also provide evidence that the dominant predator in the study system prioritizes among metabolic demands, and that these priorities may change as oxygen declines. Going forward, experiments and models should explore how differences in priorities within and among communities drive responses to environmental degradation. This will help management efforts to tailor recovery programs to the physiological needs of species within a given system.
The role of shallow and deep circulations in the Tropical Pacific Ocean heat budget
Authors: Navarro-Labastida René Gabriel , Farneti Riccardo
Published: July 2023

The Tropical Pacific Ocean plays an important role in setting the global ocean heat content and redistribution. We examined the role of the shallow and deep circulations in the tropical Pacific in unperturbed and transient climate change conditions in a global ocean model. We found that, in the Control state, the shallow circulation is by far the largest contributor to the overall balance of the column, where the balance is set as the residual between advective cooling and warming by vertical diffusive mixing. Subject to surface flux perturbations, changes in the tropical Pacific ocean heat budget can be explained by shallow wind-driven overturning circulation changes. For wind stress anomalies, the shallow ocean heat budget imbalance is directly related to overturning circulation changes, whereas under heat flux perturbations, warming of the shallow ocean is related to strengthened mid-latitude subduction and weakened dense water production at higher latitudes.
Cool skin effect and warm skin phenomenon observed by shipboard radiometer in the Northwest Pacific
Authors: Yang Minglun , Guan Lei , Qu Liqin , Zhang Kailin
Published: July 2023

Sea surface temperature (SST) is an important variable in the study of ocean boundary layers and heat exchange. The accurate simulation and measurement of skin effects are vital to air–sea model processing and satellite SST retrieval. Shipboard measurements from eleven cruises in the Northwest Pacific between August 2015 and October 2018 were used to estimate the cool skin effect and compare model results. The temperature difference ΔT between the sea surface skin temperature (SSTskin), as measured by an infrared radiometer, and the sea surface depth temperature (SSTdepth) at around 4 meters showed a mean difference and a standard deviation of the same 0.2 K, with a total of 5-min 39909 measurements. Both daytime and nighttime ΔT values were compared to physical model simulations and were found to have relatively larger mean values. A set of new coefficients for an exponential parameterization of the cool skin effect was derived in the research area, which performed well in comparison to previous empirical models. In nighttime observations from two summer cruises, the reverse process of heat flux transfer from the air to the sea in the form of a warm skin was distinguished. There were 667 positive ΔT values out of the 1917 nighttime observations, with magnitudes ranging from around 0 to 0.3 K. A high proportion of the cases of the warm skin phenomenon occurred when the air was very humid and much warmer than the sea surface.
Distribution, sources and influencing factors of organic carbon in the surface sediments of the coastal tidal flats in Jiangsu Province
Authors: Zhao Rui , Dong Xinrui , Liu Qing , Xu Min , Zhao Yifei
Published: July 2023

Coastal tidal flats are situated in the interaction zone between the ocean and land and are vulnerable to natural changes, human activities, and global changes; these areas serve as an important mixing zone and burial area for carbon and nitrogen storage. Coastal tidal flats contribute significantly to the global carbon cycle due to their high biological productivity, high sedimentation rate, and low decomposition rate. However, there is a lack of research on the sources and influencing factors of organic carbon in surface sediments in the coastal tidal flat area of Jiangsu Province. In this study, fourteen surface sediment samples were collected from the Jiangsu coastal tidal flats, and the distribution of organic carbon was analyzed. The sources and influencing factors of sediment organic carbon were also investigated by analyzing the contents, ratios and stable isotopes of carbon and nitrogen in the sediments. The results indicated that the total organic carbon (TOC) and total nitrogen (TN) contents in the surface sediments of Jiangsu coastal tidal flats ranged from 0.09% to 0.82% and from 0.01% to 0.1%, with mean values of 0.36% and 0.04%, respectively, and that there was a significant positive correlation between TOC and TN. Moreover, the high-value areas were located mostly along the borders or in sections covered in vegetation, whereas the mudflat areas without vegetation had lower values. Considering the status of the Jiangsu coastal zone, the abandoned Yellow River estuary, Yangtze River inlet, marine benthic microalgae, C3 plants and C4 plants were selected as end members of organic carbon concentrations. The contributions of different sources were quantified using a Bayesian mixture model (MixSIAR). Among them, the abandoned Yellow River estuary and Yangtze River inlet contributed 28.1% and 19.3%, respectively, followed by marine benthic microalgae with a contribution of 26%, whereas C3 and C4 plants made limited contributions of 9% and 8.8%, respectively. Additionally, the sediment particle size, hydrodynamics, and tidal flat vegetation such as Spartina alterniflora were the key factors influencing the organic carbon distribution. In general, this study contributes to a better understanding of the biogeochemical processes and sources of organic carbon in coastal tidal flats. It also provides a solid foundation for the creation of carbon sink measures in nearshore tidal flats.
Clinical, radiological, and pathological features of minute pulmonary meningothelial-like nodules and diffuse pulmonary meningotheliomatosis
Authors: Li Naijian , Quan Sicui , Liu Qin , Xie Zhiling , Wang Qiong , Wang Nian , Wang Jinlin
Published: July 2023

Background

Minute pulmonary meningothelial-like nodules (MPMNs) and diffuse pulmonary meningotheliomatosis (DPM) are both rare lung diseases that involve the proliferation of cells of meningothelial origin in the lungs. However, few studies have focused on the clinical, pathological, and radiological features of MPMNs and DPMs.

Methods

The clinicopathological data of 167 cases diagnosed as MPMNs and 13 cases diagnosed as DPM in the China National Center for Respiratory Medicine were examined. Based on clinical data, CT images, and morphological features, this study analyzed the similarities and differences between MPMNs and DPM.

Results

The detection rates of MPMNs and DPM were 1.9 and 0.15%, respectively. Compared to MPMNs, DPM patients were all women (100% vs. 79.4%, P = 0.066), had a younger age (51.4 ± 7.7 vs. 57.9 ± 8.5, P < 0.01), and had higher pulmonary function (P < 0.01 or P < 0.05). The chest CT of DPM patients showed diffuse ground-glass opacity nodules measuring 2.0–8.0 mm in diameter, with the number of nodules ranging from 40 to >600 per lung. There were no significant differences in nodule volume [28.0 (12.1, 65.1) mm3 vs. 28.7 (17.1, 48.9) mm3, P = 0.451] and CT values [−646.8 (−732.5, −514.5) Hu vs. −588 (−674, −480) Hu, P = 0.215] between MPMNs and DPM. MPMNs are characterized by reactive hyperplasia pulmonary nodules, which can be solitary or multiple.

Conclusion

This study suggests that there are many different characteristics between patients with MPMNs and DPM. The limited findings challenge the notion that DPM is a rare subtype of MPMNS.
Prediction of the occurrence of leprosy reactions based on Bayesian networks
Authors: de Andrade Rodrigues Rafael Saraiva , Heise Eduardo Ferreira José , Hartmann Luis Felipe , Rocha Guilherme Eduardo , Olandoski Marcia , de Araújo Stefani Mariane Martins , Latini Ana Carla Pereira , Soares Cleverson Teixeira , Belone Andrea , Rosa Patrícia Sammarco , de Andrade Pontes Maria Araci , de Sá Gonçalves Heitor , Cruz Rossilene , Penna Maria Lúcia Fernandes , Carvalho Deborah Ribeiro , Fava Vinicius Medeiros , Bührer-Sékula Samira , Penna Gerson Oliveira , Moro Claudia Maria Cabral , Nievola Julio Cesar , Mira Marcelo Távora
Published: July 2023

Introduction

Leprosy reactions (LR) are severe episodes of intense activation of the host inflammatory response of uncertain etiology, today the leading cause of permanent nerve damage in leprosy patients. Several genetic and non-genetic risk factors for LR have been described; however, there are limited attempts to combine this information to estimate the risk of a leprosy patient developing LR. Here we present an artificial intelligence (AI)-based system that can assess LR risk using clinical, demographic, and genetic data.

Methods

The study includes four datasets from different regions of Brazil, totalizing 1,450 leprosy patients followed prospectively for at least 2 years to assess the occurrence of LR. Data mining using WEKA software was performed following a two-step protocol to select the variables included in the AI system, based on Bayesian Networks, and developed using the NETICA software.

Results

Analysis of the complete database resulted in a system able to estimate LR risk with 82.7% accuracy, 79.3% sensitivity, and 86.2% specificity. When using only databases for which host genetic information associated with LR was included, the performance increased to 87.7% accuracy, 85.7% sensitivity, and 89.4% specificity.

Conclusion

We produced an easy-to-use, online, free-access system that identifies leprosy patients at risk of developing LR. Risk assessment of LR for individual patients may detect candidates for close monitoring, with a potentially positive impact on the prevention of permanent disabilities, the quality of life of the patients, and upon leprosy control programs.
The first rare case of Candida palmioleophila infection reported in China and its genomic evolution in a human host environment
Authors: Wu Na , Wu Yusheng , Chu Yunzhuo , Ren Zhihui , Li Hailong , Rong Chen , Yang Min , Jiang Ning , Jiang Yanyan , Chen Jingjing , Zhang Jingping , Tian Sufei
Published: July 2023

Introduction

Candida palmioleophila is a rare human pathogenic fungus, which has been poorly characterized at the genome level. In this study, we reported the first fatal case of C. palmioleophila infection in China and investigate the microevolution of C. palmioleophila in the human host environment.

Methods

A series of C. palmioleophila stains were collected from the patient at different time points for routine microbial and drug sensitivity testing. The first C. palmioleophila isolate 07202534 was identified by de novo whole genome sequencing. The in vitro and in vivo genetic evolutionary characteristics of C. palmioleophila were discussed based on the analysis of bioinformatics data.

Results

The six C. palmioleophila isolates displayed dose-dependent sensitivity to fluconazole. The C. palmioleophila genome contained homologous genes such as CDR1 and MDR1, which were recognized to be related to azole resistance. In addition, amino acid variation was detected at F105L and other important sites of ERG11. In addition, the mean divergence time between C. palmioleophila and Scheffersomyces stipites CBS 6054 was 406.04 million years, indicating that C. palmioleophila originated earlier than its closest relative. In addition, the six strains of C. palmioleophila isolated form the patient had higher homology and fewer mutation sites, which indicated the stability in C. palmioleophila genome. We also found that C. palmioleophila had a wide natural niche and may evolve slowly.

Discussion

We believe that this study will contribute to improve our understanding of the genetic evolution, pathogenicity, and drug resistance of C. palmioleophila and will aid in the prevention and control of its spread.
Identification of two novel papillomaviruses in belugas
Authors: Li Youyou , Xiao Meifang , Zhang Yun , Li Zihan , Bai Shijie , Su Haoxiang , Peng Ruoyan , Wang Gaoyu , Hu Xiaoyuan , Song Xinran , Li Xin , Tang Chuanning , Lu Gang , Yin Feifei , Zhang Peijun , Du Jiang
Published: July 2023

Introduction

Papillomaviruses (PVs) can cause hyperplasia in the skin and mucous membranes of humans, mammals, and non-mammalian animals, and are a significant risk factor for cervical and genital cancers.

Methods

Using next-generation sequencing (NGS), we identified two novel strains of papillomavirus, PV-HMU-1 and PV-HMU-2, in swabs taken from belugas (Delphinapterus leucas) at Polar Ocean Parks in Qingdao and Dalian.

Results

We amplified the complete genomes of both strains and screened ten belugas and one false killer whale (Pseudorca crassidens) for the late gene (L1) to determine the infection rate. In Qingdao, 50% of the two sampled belugas were infected with PV-HMU-1, while the false killer whale was negative. In Dalian, 71% of the eight sampled belugas were infected with PV-HMU-2. In their L1 genes, PV-HMU-1 and PV-HMU-2 showed 64.99 and 68.12% amino acid identity, respectively, with other members of Papillomaviridae. Phylogenetic analysis of combinatorial amino acid sequences revealed that PV-HMU-1 and PV-HMU-2 clustered with other known dolphin PVs but formed distinct branches. PVs carried by belugas were proposed as novel species under Firstpapillomavirinae.

Conclusion

The discovery of these two novel PVs enhances our understanding of the genetic diversity of papillomaviruses and their impact on the beluga population.
Interpreting the decisions of CNNs via influence functions
Authors: Aamir Aisha , Tamosiunaite Minija , Wörgötter Florentin
Published: July 2023

An understanding of deep neural network decisions is based on the interpretability of model, which provides explanations that are understandable to human beings and helps avoid biases in model predictions. This study investigates and interprets the model output based on images from the training dataset, i.e., to debug the results of a network model in relation to the training dataset. Our objective was to understand the behavior (specifically, class prediction) of deep learning models through the analysis of perturbations of the loss functions. We calculated influence scores for the VGG16 network at different hidden layers across three types of disturbances in the original images of the ImageNet dataset: texture, style, and background elimination. The global and layer-wise influence scores allowed the identification of the most influential training images for the given testing set. We illustrated our findings using influence scores by highlighting the types of disturbances that bias predictions of the network. According to our results, layer-wise influence analysis pairs well with local interpretability methods such as Shapley values to demonstrate significant differences between disturbed image subgroups. Particularly in an image classification task, our layer-wise interpretability approach plays a pivotal role to identify the classification bias in pre-trained convolutional neural networks, thus, providing useful insights to retrain specific hidden layers.
Anthropological perspectives on CKDnt in Mexico: time for a paradigm shift on the social determinants of health
Authors: Kierans Ciara , Padilla-Altamira Cesar
Published: July 2023

In Mexico, the kidneys of individuals in poor and marginalized communities are failing with little warning and no explanation. Commonly referred to as chronic kidney disease of non-traditional origin (CKDnt), this new variant of kidney disease cannot be accounted for by conventional or discrete etiological explanations, but is instead understood to be a consequence of economic development, environmental degradation and precarious working and living conditions. Drawing on two interconnected ethnographic studies, and the intertwining problems of causation and care, this paper will (1) document the social conditions of disease emergence around Lake Chapala, Central Mexico, and (2) follow the haphazard routes kidney patients take to access resource-intensive biotechnical treatments. Its aim is to both challenge and reconceptualize social determinantsassocial relations in order to fully account for the profoundly contextual, temporal, and dynamic character of this condition, and to rethink opportunities for care and intervention.
Healthcare resource utilization and costs associated with generalized myasthenia gravis: a retrospective matched cohort study using the National Health Insurance Research Database in Taiwan
Authors: Shen Shih-Pei , Herr Keira Joann , Liu Yanfang , Yang Chih-Chao , Tang Chao-Hsiun
Published: July 2023

Background

We estimated healthcare resource utilization (HRU) and costs in patients with generalized myasthenia gravis (gMG) in Taiwan.

Methods

This retrospective population-based, matched cohort study used the National Health Insurance Research Database to identify prevalent patients with gMG (cases) in 2019. In total, 2537 cases were matched (1:4) by age, sex, and urbanization level to 10148 randomly selected patients without gMG (comparators). A generalized linear regression model predicted the frequency of HRU and costs among service users. Costs attributable to gMG were obtained by subtracting all-cause HRU costs incurred by comparators from cases.

Results

The mean age of all patients was 54.99 years and 55.97% were female. Compared with comparators, cases had significantly higher rates of hypertension (33.03%/24.26%), diabetes mellitus (18.92%/11.37%), malignancies (16.00%/4.08%), cardiovascular disease (11.35%/8.12%), thyroid-related conditions (5.99%/1.16%), respiratory illness/disorders (4.38%/1.22%), and neurotic disorders (4.65%/2.6%). Amongst users of healthcare resources, cases had a mean 10 additional outpatient visits, 0.62 inpatient stays, and 0.49 emergency room visits in 2019 compared with comparators (p < 0.0001 for all). The mean (standard deviation) difference in all-cause healthcare costs between cases and comparators was NT$ 94997 (76431) [US$ 3133 (2521)], and was significantly higher for all categories (outpatient, inpatient, emergency room, drugs; p < 0.0001 for all). Among employed persons, 13.18%/7.59% of cases/comparators changed employment status during the study (p < 0.0001).

Conclusion

gMG presents a substantial burden on HRU and healthcare costs in Taiwan. A high attrition rate from full-time employment suggests additional societal costs. Improved treatments are needed to alleviate the burden of disease on individuals, healthcare systems, and economies.
Ataxia-telangiectasia in China: a case report of a novel ATM variant and literature review
Authors: Shao Li , Wang Haoyi , Xu Jianbo , Qi Ming , Yu Zhaonan , Zhang Jing
Published: July 2023

Background

Ataxia-telangiectasia (A-T) is a multisystem genetic disorder involving ataxia, oculocutaneous telangiectasia, and immunodeficiency caused by biallelic pathogenic variants in the ATM gene. To date, most ATM variants have been reported in the Caucasian population, and few studies have focused on the genotype–phenotype correlation of A-T in the Chinese population. We herein present a Chinese patient with A-T who carries compound heterozygous variants in the ATM gene and conducted a literature review for A-T in China.

Case presentation

A 7-year-old Chinese girl presented with growth retardation, ataxia, medium ocular telangiectasia, cerebellar atrophy, and elevated serum alpha-fetoprotein (AFP) level, which supported the suspicion of A-T. Notably, the serum levels of immunoglobulins were all normal, ruling out immunodeficiency. Exome sequencing and Sanger sequencing revealed two likely pathogenic ATM variants, namely NM_000051.4: c.4195dup (p.Thr1399Asnfs*15) and c.6006 + 1G>T (p.?), which were inherited from her father and mother, respectively. From the Chinese literature review, we found that there was a marked delay in the diagnosis of A-T, and 38.9% (7/18) of A-T patients did not suffer from immunodeficiency in China. No genotype–phenotype correlation was observed in this group of A-T patients.

Conclusion

These results extend the genotype spectrum of A-T in the Chinese population and imply that the diagnosis of A-T in China should be improved.
How neurons maintain their axons long-term: an integrated view of axon biology and pathology
Authors: Smith Gaynor , Sweeney Sean T. , O’Kane Cahir J. , Prokop Andreas
Published: July 2023

Axons are processes of neurons, up to a metre long, that form the essential biological cables wiring nervous systems. They must survive, often far away from their cell bodies and up to a century in humans. This requires self-sufficient cell biology including structural proteins, organelles, and membrane trafficking, metabolic, signalling, translational, chaperone, and degradation machinery—all maintaining the homeostasis of energy, lipids, proteins, and signalling networks including reactive oxygen species and calcium. Axon maintenance also involves specialised cytoskeleton including the cortical actin-spectrin corset, and bundles of microtubules that provide the highways for motor-driven transport of components and organelles for virtually all the above-mentioned processes. Here, we aim to provide a conceptual overview of key aspects of axon biology and physiology, and the homeostatic networks they form. This homeostasis can be derailed, causing axonopathies through processes of ageing, trauma, poisoning, inflammation or genetic mutations. To illustrate which malfunctions of organelles or cell biological processes can lead to axonopathies, we focus on axonopathy-linked subcellular defects caused by genetic mutations. Based on these descriptions and backed up by our comprehensive data mining of genes linked to neural disorders, we describe the ‘dependency cycle of local axon homeostasis’ as an integrative model to explain why very different causes can trigger very similar axonopathies, providing new ideas that can drive the quest for strategies able to battle these devastating diseases.
Strain-specific changes in nucleus accumbens transcriptome and motivation for palatable food reward in mice exposed to maternal separation
Authors: Benoit Simon , Henry Mathilde , Fneich Sara , Mathou Alexia , Xia Lin , Foury Aline , Jouin Mélanie , Junien Claudine , Capuron Lucile , Jouneau Luc , Moisan Marie-Pierre , Delpierre Cyrille , Gabory Anne , Darnaudéry Muriel
Published: July 2023

Introduction

In humans, adversity in childhood exerts enduring effects on brain and increases the vulnerability to psychiatric diseases. It also leads to a higher risk of eating disorders and obesity. Maternal separation (MS) in mice has been used as a proxy of stress during infancy. We hypothesized that MS in mice affects motivation to obtain palatable food in adulthood and changes gene expression in reward system.

Methods

Male and female pups from C57Bl/6J and C3H/HeN mice strains were subjected to a daily MS protocol from postnatal day (PND) 2 to PND14. At adulthood, their motivation for palatable food reward was assessed in operant cages.

Results

Compared to control mice, male and female C3H/HeN mice exposed to MS increased their instrumental response for palatable food, especially when the effort required to obtain the reward was high. Importantly, this effect is shown in animals fed ad libitum. Transcriptional analysis revealed 375 genes differentially expressed in the nucleus accumbens of male MS C3H/HeN mice compared to the control group, some of these being associated with the regulation of the reward system (e.g., Gnas, Pnoc). Interestingly, C57Bl/6J mice exposed to MS did not show alterations in their motivation to obtain a palatable reward, nor significant changes in gene expression in the nucleus accumbens.

Conclusion

MS produces long-lasting changes in motivation for palatable food in C3H/HeN mice, but has no impact in C57Bl/6J mice. These behavioral alterations are accompanied by drastic changes in gene expression in the nucleus accumbens, a key structure in the regulation of motivational processes.
Nutritional, bioactive compounds content, and antioxidant activity of brown seaweeds from the Red Sea
Authors: Ismail Mona M. , El Zokm Gehan M. , Miranda Lopez José M.
Published: July 2023

Introduction

Brown seaweeds are excellent sources of bioactive molecules with a wide range of pharmacological effects, whose content can vary depending on several factors, including the origin and the environment in which the algae grow.

Methods

This study aimed to estimate 19 compounds regarding primary and secondary metabolites of eight brown macroalgal species from a clean Egyptian Red Sea coast. A proximate analysis, pigment, phenolic compounds, and vitamin contents were determined. In addition, the energy content and antioxidant activity were estimated to explore the potential application of algae as functional foods to encourage the species’ commercialization.

Results

Based on the chemical composition, Polycladia myrica was the most valuable species, with a comparatively high protein content of 22.54%, lipid content of 5.21%, fucoxanthin content of 3.12 μg/g, β-carotene content of 0.55 mg/100 g, and carbohydrate content of 45.2%. This species also acts as a great source of vitamin C, flavonoids, tannins, phenol content and total antioxidant capacity.

Discussion

The antioxidant activity of the selected algae indicated that its phenol, vitamin and pigment contents were powerful antioxidant compounds based on the structure–activity relationships. This result was verified by the strong correlation in statistical analysis at the 95% confidence level. From a worldwide perspective and based on the obtained results, these brown species may be reinforced as an essential line in future foods.
Questionnaire-based analysis of autism spectrum disorders and gastrointestinal symptoms in children and adolescents: a systematic review and meta-analysis
Authors: Gan Huizhong , Su Yanhong , Zhang Linlin , Huang Guolin , Lai Ciai , Lv Ying , Li Yongchun
Published: July 2023

Background

Gastrointestinal (GI) symptoms are frequently experienced by children with autism spectrum disorder (ASD), and these symptoms cause difficulties for these children and their families. However, studies of GI symptom prevalence differ significantly. This meta-analysis aimed to analyze the prevalence of GI symptoms in children with ASD.

Methods and findings

PubMed, Scopus, Web of Science, EMBASE were electronically searched to collect all literature on gastrointestinal symptoms of children with ASD collected through questionnaires or scales from January 2012 to May 2021. Four researchers independently scanned the literature and extracted information on general characteristics. First author name, year of publication, geographical location, type of study, sample sizes of ASD and control (if any) children, sex and average age, number of GI cases, number of GI symptoms, GI assessment tools (gastrointestinal symptoms scale), autism diagnosis methods, and other necessary data were collected and analyzed using Stata V16. The questionnaires included the Rome, 6-GSI, GIQ, GSRS, GSIQ, ADI-R, PedsQL-GI, parent-report, GI-related, and self-administered questionnaires. Compared with typically developing (TD) children, the odds ratio for In children with ASD with at least one GI symptom was 3.64, and the total prevalence was 55%. The cumulative prevalence rates of various symptoms were summarized, showing that 37% of children with ASD had constipation, 21% had abdominal pain, 19% had diarrhea, 8% had vomiting, and 23% had abdominal distension.

Conclusions

The results of this meta-analysis on GI symptoms in ASD show that patients with ASD are more likely to develop symptoms than TD children. The prevalence of GI symptoms in In children with ASD was 55%.

Systematic Review Registration

www.crd.york.ac.uk/PROSPERO, identifier, #CRD42017080579.