bluuebunny/crossref_metadata_2025 huggingface dataset:
Mangrove Growth Monitoring Based on Camera Visible Images—A Case Study on Typical Mangroves in Guangxi
Authors: Chen Yanli , Fang Shibo , Sun Ming , Liu Zhiping , Pan Lianghao , Mo Weihua , Chen Cheng
Published: February 2022

Mangroves are an important coastal wetland ecosystem, and the high-throughput visible light (RGB) images of the canopy obtained by the ecological meteorological station can provide basic data for quantitative and continuous growth monitoring of mangroves. However, as for the mangroves that are subject to periodic seawater submersion, some key technical issues such as image selection, vegetation segmentation, and index applicability remain unsolved. With the typical mangroves in Beihai, Guangxi, as the object in this study, we used canopy RGB images and tidal data to find out the screening methods for high-quality nontidal submerged images, as well as the vegetation segmentation algorithms and RGB vegetation index applicability, so as to provide technical reference for the use of RGB images to monitor mangrove growth. The results showed that: 1) The critical tide levels can be determined according to the periodic changes of submersion in the mangroves, and critical tidal levels and image brightness can be used to quickly screen high-quality images of mangroves that are not submerged by seawater. 2) Machine learning and NLM filtering are effective strategies to obtain high-precision mangrove segmentation results. The machine learning algorithm has superiority in the segmentation of mangrove vegetation with a segmentation accuracy of higher than 80%, and the nonlocal mean filtering can effectively optimize the segmentation results of various algorithms. 3) The seasonal index VEG and antiseasonal index CIVE can be used as the optimal indices for mangrove growth monitoring, and the compound sine function can better simulate the change trend of various RGB vegetation indices, which is convenient for quickly judging mangrove growth changes. 4) Mangrove RGB vegetation indices are sensitive to meteorological factors and can be used to analyze the influence of meteorological conditions on mangrove growth.
Fracture Characteristics and Reservoir Inhomogeneity Prediction of the Gaoyuzhuang Formation in the Xiong’an New Area: Insights From a 3D Discrete Fracture Network Model
Authors: Yue Gaofan , Wang Guiling , Ma Feng , Zhu Xi , Zhang Hanxiong , Zhou Jianwei , Na Jin
Published: February 2022

The Xiong’an new area in northern China is rich in geothermal resources. The Gaoyuzhuang Formation in the Proterozoic Jixian system is an important recently discovered geothermal reservoir. The Gaoyuzhuang reservoir has been affected by multiple stages of tectonic movement. The fractures are very well developed, resulting in strong heterogeneity in the reservoir’s porosity and permeability. Few studies have been conducted on the fractures and heterogeneity of the Gaoyuzhuang reservoir. In this study, interpretation of data from image logs was used to summarize the characteristics of the fractures, including the fractures’ strikes, dips, and lengths. The permeability distribution of the reservoir in the vicinity of the borehole was predicted. The hydro-thermal (TH) coupling model was used to reproduce the process of pumping tests, and the simulation results were found to be in good agreement with the field test data. In addition, the relationship between the fracture aperture and length was obtained, dmax=4.2×10−5⋅L0.5. The results of this study provide data and technical support for further reservoir research and evaluation of the geothermal resources of the Gaoyuzhuang reservoir.
DMRT2 Interacts With FXR and Improves Insulin Resistance in Adipocytes and a Mouse Model
Authors: Tao Jing , Yu Xiao-Lin , Yuan Yu-Juan , Shen Xin , Liu Jun , Gu Pei-Pei , Wang Zhao , Ma Yi-Tong , Li Guo-Qing
Published: February 2022

Insulin resistance (IR) plays a critical role in cardiovascular diseases and metabolic diseases. In this study, we identified the downregulation of DMRT2 in adipose tissues from insulin-resistant subjects through bioinformatics analysis and in an insulin-resistant mouse model through experimental analysis. DMRT2 overexpression significantly attenuated HDF-induced insulin resistance and inflammation in mice. Moreover, in control and insulin-resistant differentiated mouse 3T3-L1 adipocytes, DMRT2 overexpression attenuated but DMRT2 knockdown enhanced the insulin resistance of 3T3-L1 adipocytes. DMRT2 interacted with FXR and positively regulated FXR level and transcription activity. In both control and insulin-resistant differentiated mouse 3T3-L1 adipocytes, FXR knockdown enhanced the insulin resistance and attenuated the effects of DMRT2 overexpression upon 3T3-L1 adipocyte insulin resistance. In conclusion, we identify the downregulation of DMRT2 in the insulin-resistant mouse model and cell model. DMRT2 interacts with FXR and improves insulin resistance in adipocytes.
A Qualitative Exploration of Self-Management Behaviors and Influencing Factors in Patients With Type 2 Diabetes
Authors: Peng Xi , Guo Xinhong , Li Hongmei , Wang Dan , Liu Chenxi , Du Yaling
Published: February 2022

Background and Aims

The self-management behavior of patients with diabetes involves a complex set of actions involving medication therapy, lifestyle changes, and management of complications in the daily routine. Our study aims to explore adherence to self-management behaviors by patients with type 2 diabetes and the potential factors influencing those behaviors.

Methods

This qualitative study used semi-structured interviews conducted with patients who have type 2 diabetes and who were recruited from the department of endocrinology in a tertiary teaching hospital. Data were analyzed thematically using the interview framework.

Results

Overall, 28 patients with type 2 diabetes were recruited and interviewed. Three types of medication noncompliance behaviors were coded. In particular, blindly optimistic attitudes toward the condition in younger patients who had a short duration of diabetes and fear of or pain from medication therapy were key influencing factors. Irregular monitoring and missed follow-up visits were the most frequently mentioned noncompliance behaviors. Poor understanding of blood glucose monitoring, selective ignorance due to pressure of uncontrolled blood glucose, and blindly optimistic attitudes were also identified as key influencing factors. Dietary behaviors were characterized by an overemphasis on the amount of food in the diet and the preference or declination for particular types of food; ignorance of the dietary structure was present. Misconceptions about dietary and exercise practices were the main types of lifestyles’ noncompliance.

Conclusion

Our study showed the complex picture of noncompliance with self-management behaviors by patients with type 2 diabetes. Noncompliance covered disordered and arbitrary changes in medication therapy, blood glucose monitoring with poorest adherence, lifestyle modifications and complication management. The study findings identify clear challenges to self-management behavior and identify potential key influencing factors. Future interventions and strategies should aim to help patients translate healthcare provider’s information and instructions into action that improve compliance.
Focus on Hyperparasites: Biotic and Abiotic Traits Affecting the Prevalence of Parasitic Microfungi on Bat Ectoparasites
Authors: Péter Áron , Mihalca Andrei Daniel , Haelewaters Danny , Sándor Attila D.
Published: February 2022

The tritrophic association of bats, bat flies, and Laboulbeniales microfungi is a remarkably understudied system that may reveal patterns applicable to community ecology theory of (hyper)parasites. Laboulbeniales are biotrophic microfungi, exclusively associated with arthropods, with several species that are specialized on bat flies, which themselves are permanent ectoparasites of bats. Several hypotheses were tested on biotic and abiotic traits that may influence the presence and prevalence of hyperparasitic Laboulbeniales fungi on bat flies, based on southeastern European data. We found a wide distribution of fungal infection on bat flies, with underground-dwelling bats hosting more Laboulbeniales-infected flies compared to crevice-dwelling species. Bat host behavior, sociality, roost selection (underground versus crevice), bat fly sex, and season all have significant effects on the prevalence of fungal infection. Laboulbeniales infections are more common on bat flies that are infecting bat species with dense and long-lasting colonies (Miniopterus schreibersii, Myotis myotis, Myotis blythii), which roost primarily in underground sites. Inside these sites, elevated temperature and humidity may enhance the development and transmission of Laboulbeniales fungi. Sexual differences in bat hosts’ behavior also have an effect on fungal infection risk, with densely roosting female bat hosts harboring more Laboulbeniales-infected bat flies.
Identification of a Novel Missense Mutation of the PHEX Gene in a Large Chinese Family with X-Linked Hypophosphataemia
Authors: Yang Yanting , Wang Yuanda , Shen Ying , Liu Mohan , Dai Siyu , Wang Xiaodong , Liu Hongqian
Published: February 2022

X-linked hypophosphataemia (XLH) is an X-linked dominant rare disease that refers to the most common hereditary hypophosphatemia (HH) caused by mutations in the phosphate-regulating endopeptidase homolog X-linked gene (PHEX; OMIM: * 300550). However, mutations that have already been reported cannot account for all cases of XLH. Extensive genetic analysis can thus be helpful for arriving at the diagnosis of XLH. Herein, we identified a novel heterozygous mutation of PHEX (NM_000444.5: c.1768G > A) in a large Chinese family with XLH by whole-exome sequencing (WES). In addition, the negative effect of this mutation in PHEX was confirmed by both bioinformatics analysis and in vitro experimentation. The three-dimensional protein-model analysis predicted that this mutation might impair normal zinc binding. Immunofluorescence staining, qPCR, and western blotting analysis confirmed that the mutation we detected attenuated PHEX protein expression. The heterozygous mutation of PHEX (NM_000444.5: c.1768G > A) identified in this study by genetic and functional experiments constitutes a novel genetic cause of XLH, but further study will be required to expand its use in clinical and molecular diagnoses of XLH.
Genome-Wide Identification of Immune-Related Alternative Splicing and Splicing Regulators Involved in Abdominal Aortic Aneurysm
Authors: Wu Shiyong , Liu Shibiao , Chen Ningheng , Zhang Chuang , Zhang Hairong , Guo Xueli
Published: February 2022

The molecular mechanism of AAA formation is still poorly understood and has not been fully elucidated. The study was designed to identify the immune-related genes, immune-RAS in AAA using bioinformatics methods. The GSE175683 datasets were downloaded from the GEO database. The DEseq2 software was used to identify differentially expressed genes (DEGs). SUVA pipeline was used to quantify AS events and RAS events. KOBAS 2.0 server was used to identify GO terms and KEGG pathways to sort out functional categories of DEGs. The CIBERSORT algorithm was used with the default parameter for estimating immune cell fractions. Nine samples from GSE175683 were used to construct the co-disturbed network between expression of SFs and splicing ratio of RAS events. PCA analysis was performed by R package factoextra to show the clustering of samples, and the pheatmap package in R was used to perform the clustering based on Euclidean distance. The results showed that there were 3,541 genes significantly differentially expressed, of which 177 immune-related genes were upregulated and 48 immune-related genes were downregulated between the WT and WTA group. Immune-RAS events were mainly alt5P and IR events, and about 60% of it was complex splicing events in AAA. The WT group and the WTA group can be clearly distinguished in the first principal component by using the splicing ratio of immune-RAS events. Two downregulated genes, Nr4a1 and Nr4a2, and eight upregulated genes, Adipor2, Akt2, Bcl3, Dhx58, Pparg, Ptgds, Sytl1, and Vegfa were identified among the immune-related genes with RAS and DEGs. Eighteen differentially expressed SFs were identified and displayed by heatmap. The proportion of different types of cells and ratio of the average ratio of different cells were quite different. Both M1 and M2 types of macrophages and plasma cells were upregulated, while M0 type was downregulated in AAA. The proportion of plasma cells in the WTA group had sharply increased. There is a correlation between SF expression and immune cells/immune-RAS. Sf3b1, a splicing factor with significantly different expression, was selected to bind on a mass of immune-related genes. In conclusion, our results showed that immune-related genes, immune-RAS, and SFs by genome-wide identification were involved in AAA.
Blood-Enriching Effects and Immune-Regulation Mechanism of Steam-Processed Polygonatum Sibiricum Polysaccharide in Blood Deficiency Syndrome Mice
Authors: Wang Juan , Wang Furong , Yuan Lixia , Ruan Hongsheng , Zhu Zhibiao , Fan Xiaoling , Zhu Lingyan , Peng Xin
Published: February 2022

Polygonatum sibiricum Red. has been used as a medicinal herb and nutritional food in traditional Chinese medicine for a long time. It must be processed prior to clinical use for safe and effective applications. However, the present studies mainly focused on crude Polygonatum sibiricum (PS). This study aimed to investigate the chemical properties, blood-enriching effects and mechanism of polysaccharide from the steam-processed Polygonatum sibiricum (SPS), which is a common form of PS in clinical applications. Instrumentation analyses and chemistry analyses revealed the structure of SPS polysaccharide (SPSP). A mice model of blood deficiency syndrome (BDS) was induced by acetylphenylhydrazine (APH) and cyclophosphamide (CTX). Blood routine test, spleen histopathological changes, serum cytokines, etc. were measured. The spleen transcriptome changes of BDS mice were detected by RNA sequencing (RNA-seq). The results showed that SPSP consists predominantly of Gal and GalA together with fewer amounts of Man, Glc, Ara, Rha and GlcN. It could significantly increase peripheral blood cells, restore the splenic trabecular structure, and reverse hematopoietic cytokines to normal levels. RNA-seq analysis showed that 122 differentially expressed genes (DEGs) were obtained after SPSP treatment. GO and KEGG analysis revealed that SPSP-regulated DEGs were mainly involved in hematopoiesis, immune regulation signaling pathways. The reliability of transcriptome profiling was validated by quantitative real-time PCR and Western blot, and the results indicated that the potential molecular mechanisms of the blood-enriching effects of SPSP might be associated with the regulating of JAK1-STAT1 pathway, and elevated the hematopoietic cytokines (EPO, G-CSF, TNF-α and IL-6). This work provides important information on the potential mechanisms of SPSP against BDS.
Activation of Complement Components on Circulating Blood Monocytes From COVID-19 Patients
Authors: Lage Silvia Lucena , Rocco Joseph M. , Laidlaw Elizabeth , Rupert Adam , Galindo Frances , Kellogg Anela , Kumar Princy , Poon Rita , Wortmann Glenn W. , Lisco Andrea , Manion Maura , Sereti Irini
Published: February 2022

The coronavirus disease-2019 (COVID-19) caused by the SARS-CoV-2 virus may vary from asymptomatic to severe infection with multi-organ failure and death. Increased levels of circulating complement biomarkers have been implicated in COVID-19-related hyperinflammation and coagulopathy. We characterized systemic complement activation at a cellular level in 49-patients with COVID-19. We found increases of the classical complement sentinel C1q and the downstream C3 component on circulating blood monocytes from COVID-19 patients when compared to healthy controls (HCs). Interestingly, the cell surface-bound complement inhibitor CD55 was also upregulated in COVID-19 patient monocytes in comparison with HC cells. Monocyte membrane-bound C1q, C3 and CD55 levels were associated with plasma inflammatory markers such as CRP and serum amyloid A during acute infection. Membrane-bounds C1q and C3 remained elevated even after a short recovery period. These results highlight systemic monocyte-associated complement activation over a broad range of COVID-19 disease severities, with a compensatory upregulation of CD55. Further evaluation of complement and its interaction with myeloid cells at the membrane level could improve understanding of its role in COVID-19 pathogenesis.
A High Prevalence of Anti-EBNA1 Heteroantibodies in Systemic Lupus Erythematosus (SLE) Supports Anti-EBNA1 as an Origin for SLE Autoantibodies
Authors: Laurynenka Viktoryia , Ding Lili , Kaufman Kenneth M. , James Judith A. , Harley John B.
Published: February 2022

Background

That Epstein–Barr virus (EBV) infection is associated with systemic lupus erythematosus (SLE) is established. The challenge is to explain mechanistic roles EBV has in SLE pathogenesis. Previous studies identify four examples of autoantibody cross-reactions between SLE autoantigens and Epstein–Barr nuclear antigen 1 (EBNA1). For two of these examples, the earliest detected autoantibody specifically cross-reacts with EBNA1; thereby, defined EBNA1 epitopes induce a robust autoantibody response in animals. These results suggest that the autoantibodies initiating the process leading to SLE may emerge from the anti-EBNA1 heteroimmune response. If this hypothesis is true, then anti-EBNA1 responses would be more frequent in EBV-infected SLE patients than in EBV-infected controls. We tested this prediction.

Methods

We evaluated published East Asian data by selecting those with a positive anti-viral capsid antigen (VCA) antibody immunoglobulin G (IgG) test and determining whether anti-EBNA1 was more common among the EBV-infected SLE cases than among matched EBV-infected controls with conditional logistic regression analysis.

Results

All the qualifying SLE patients (100%) in this dataset were EBV-infected compared to age- and sex-matched controls (92.2%) [odds ratio (OR) = 28.6, 95% CI 6.4–∞, p = 8.83 × 10-8], confirming the known close association of EBV infection with SLE. Furthermore, virtually all the SLE cases have both anti-VCA IgG and anti-EBNA1 IgG antibodies [124 of 125 (99.2%)], which are more frequently present than in age- and sex-matched EBV-infected controls [232 of 250 (93.2%)] (OR = 9.7, 95% CI 1.5–414, p = 0.0078) for an 89.7% SLE attributable risk from anti-EBNA1, which is in addition to the 100% SLE risk attributable to EBV infection in these data.

Conclusions

The association of EBV infection with SLE is reconfirmed. The prediction that anti-EBNA1 is more frequent in these SLE cases than in EBV-infected controls is true, consistent with the hypothesis that anti-EBNA1 contributes to SLE. This second EBV-dependent risk factor is consistent with a molecular mimicry model for the generation of SLE, starting with EBV infection, progressing to anti-EBNA1 response; then molecular mimicry leads to anti-EBNA1 antibodies cross-reacting with an SLE autoantigen, causing autoantibody epitope spreading, and culminating in clinical SLE. These results support the anti-EBNA1 heteroimmune response being a foundation from which pathogenic SLE autoimmunity emerges.
LPS Guides Distinct Patterns of Training and Tolerance in Mast Cells
Authors: De Zuani Marco , Dal Secco Chiara , Tonon Silvia , Arzese Alessandra , Pucillo Carlo E. M. , Frossi Barbara
Published: February 2022

Mast cells (MCs) are tissue-resident, long lived innate immune cells with important effector and immunomodulatory functions. They are equipped with an eclectic variety of receptors that enable them to sense multiple stimuli and to generate specific responses according on the type, strength and duration of the stimulation. Several studies demonstrated that myeloid cells can retain immunological memory of their encounters – a process termed ‘trained immunity’ or ‘innate immune memory’. As MCs are among the one of first cells to come into contact with the external environment, it is possible that such mechanisms of innate immune memory might help shaping their phenotype and effector functions; however, studies on this aspect of MC biology are still scarce. In this manuscript, we investigated the ability of MCs primed with different stimuli to respond to a second stimulation with the same or different ligands, and determined the molecular and epigenetic drivers of these responses. Our results showed that, while the stimulation with IgE and β-glucan failed to induce either tolerant or trained phenotypes, LPS conditioning was able to induce a profound and long-lasting remodeling of the signaling pathways involved in the response against LPS or fungal pathogens. On one side, LPS induced a strong state of unresponsiveness to secondary LPS stimulation due to the impairment of the PI3K-AKT signaling pathway, which resulted in the reduced activation of NF-κB and the decreased release of TNF-α and IL-6, compared to naïve MCs. On the other side, LPS primed MCs showed an increased release of TNF-α upon fungal infection with live Candida albicans, thus suggesting a dual role of LPS in inducing both tolerance and training phenotypes depending on the secondary challenge. Interestingly, the inhibition of HDAC during LPS stimulation partially restored the response of LPS-primed MCs to a secondary challenge with LPS, but failed to revert the increased cytokine production of these cells in response to C. albicans. These data indicate that MCs, as other innate immune cells, can develop innate immune memory, and that different stimulatory environments can shape and direct MC specific responses towards the dampening or the propagation of the local inflammatory response.
Targeting TNFR2 in Cancer: All Roads Lead to Rome
Authors: Bai Jingchao , Ding Bowen , Li Hui
Published: February 2022

TNF receptor 2 (TNFR2) has become one of the best potential immune checkpoints that might be targeted, mainly because of its vital role in tumor microenvironments (TMEs). Overexpression of TNFR2 in some tumor cells and essential function in immunosuppressive cells, especially regulatory T cells (Tregs), makes blocking TNFR2 an excellent strategy in cancer treatment; however, there is evidence showing that activating TNFR2 can also inhibit tumor progressionin vivo. In this review, we will discuss drugs that block and activate TNFR2 under clinical trials or preclinical developments up till now. Meanwhile, we summarize and explore the possible mechanisms related to them.
Asphalt Binder Testing at Low Temperature: Three-Point Bending Beam Test in Dynamic Shear Rheometer
Authors: Kim Yun Su , Büchner Johannes , Wistuba Michael P. , Agudo José Rodríguez , Rochlani Mrinali , Schäffler Michael
Published: February 2022

A novel Three-Point Bending Beam Test (3-PBT) using a Dynamic Shear Rheometer (DSR) with linear drive motor is introduced for testing asphalt binder at low temperature conditions. This 3-PBT in DSR can be used as surrogate for Bending Beam Rheometer (BBR) tests. Advantages in comparison to BBR are that (i) 3-PBT works without harmful cooling medium ethanol, (ii) the amount of asphalt binder for testing is significantly lower (using material equivalent of 10% of BBR tests), (iii) a silicone rubber mold is used for specimen preparation instead of standard aluminum mold for BBR tests, which makes handling easier, and (iv) the loading protocol is more practical without applying contact load manually. The novel 3-PBT in DSR is presented with respect to preparation, installation, and conditioning of specimens, as well as to the loading protocol. Tests were conducted at temperatures of −10, −16, and −20°C. For the purpose of comparison to BBR tests, and of identifying most suitable testing conditions from alternative setups, a test series was run including 9 different asphalt binders. As to BBR tests, two different cooling media were used, i.e., ethanol and air. Finally, all test results obtained from DSR and BBR tests were analyzed in view of precision and correlation. DSR results correlated well with BBR results, while precision of 3-PBT in DSR was found to be satisfying.
A Pilot Nurse-Led Tele-Counseling Intervention to Parents of Children With Cerebral Visual Impairment on Adherence to Eye Activities During COVID-19 Pandemic: A Pre-experimental Study
Authors: Dhiman Sonam , Saini Sushma Kumari , Chaurasia Shweta , Duggal Mona , Miglani Vaibhav , Raj Srishti
Published: February 2022

Aim

To assess the impact of a culturally appropriate and theoretically driven nurse-led tele-counseling intervention to parents of children with cerebral visual impairment (CVI) on the adherence to visual therapy advised by the ophthalmologists.

Design

A pre-experimental design was used.

Methods

Parents of children with CVI aged 2–9 years were enroled telephonically during the coronavirus disease 2019 (COVID-19) pandemic through the Pediatric Ophthalmology Clinic of a tertiary eye care center. Pre-assessment of participants was done telephonically as per the interview schedule. As per the protocol, the trained nurse-delivered tele-counseling intervention two times weekly for the first 2 weeks and weekly for the next 2 weeks via audio and video two-way tele-interaction with parents. A CVI information booklet was shared with parents via WhatsApp interface and individualized visual therapy was reinforced in accordance with the advice of the treating ophthalmologist. It was based on a thorough review of clinical records of the child, such as a detailed CVI questionnaire, history, and findings of clinical examination and neuro-visual behavior of a child. In addition, parents were encouraged to maintain a diary of the daily sessions of visual therapy and share recorded videos of their training exercises which were then evaluated and discussed with the ophthalmologist for any deviation. Outcome measures included adherence to eye activities for 7–8 sessions per day. Data were analyzed by using SPSS statistics for windows, version 20.

Results

Overall, improvement of adherence to visual therapy was observed among children with CVI (p < 0.0001). Nearly half (47.6%) of participants adhered to 3–4 sessions/day and only 28.6% were adherent to the recommended 7–8 sessions/day.

Conclusion

The pilot study demonstrated the potential of the nurse-led tele-counseling intervention to supplement the ongoing health treatment of patients in improving the adherence to eye activities among parents of children with CVI.
IL-13 and IL-33 Serum Levels Are Increased in Systemic Sclerosis Patients With Interstitial Lung Disease
Authors: Versace Antonio Giovanni , Bitto Alessandra , Ioppolo Carmelo , Aragona Caterina Oriana , La Rosa Daniela , Roberts William Neal , D'Angelo Tommaso , Cinquegrani Antonella , Cirmi Santa , Irrera Natasha , Navarra Michele , Corrao Salvatore , Gangemi Sebastiano , Bagnato Gianluca
Published: February 2022

Objective

Systemic sclerosis (SSc) mortality is extremely variable in its internal organ involvement. Pulmonary fibrosis occurs in up to 30% of the cases. Animal models provide evidence that IL-33 is able to induce both cutaneous and pulmonary fibrosis via increased IL-13 and in SSc patients the levels of IL-33 correlate with skin fibrosis. Our aim was to test whether both IL-33 and IL-13 are higher in patients with diffuse SSc and interstitial lung disease (SSc-ILD) compared to SSc patients without ILD and healthy controls.

Methods

Serum levels of IL-13 and IL-33 were measured in 30 SSc patients with diffuse disease and 30 healthy controls by enzyme-linked immunosorbent assay. The extent of pulmonary fibrosis was assessed according to HRCT Warrick score. Pulmonary function tests included lung diffusion capacity for carbon monoxide, forced vital capacity and total lung capacity.

Results

Both IL-13 and IL-33 levels were increased in SSc patients compared to controls and significantly associated each other. DLco, FVC and TLC scores were inversely associated with IL-33 and IL-13 levels. Both IL-33 and IL-13 levels were significantly associated with the Warrick severity score and higher in the group of SSc patients with reduced pulmonary function compared to SSc patients with normal pulmonary function tests.

Conclusion

The IL-13/IL-33 axis needs to be further explored in longitudinal studies of SSc-ILD patients to assess its validity as a biomarker and future treatment target, as does downstream mediator ST2.
Genomic Analysis of Molecular Bacterial Mechanisms of Resistance to Phage Infection
Authors: Ambroa Antón , Blasco Lucia , López María , Pacios Olga , Bleriot Inés , Fernández-García Laura , González de Aledo Manuel , Ortiz-Cartagena Concha , Millard Andrew , Tomás María
Published: February 2022

To optimize phage therapy, we need to understand how bacteria evolve against phage attacks. One of the main problems of phage therapy is the appearance of bacterial resistance variants. The use of genomics to track antimicrobial resistance is increasingly developed and used in clinical laboratories. For that reason, it is important to consider, in an emerging future with phage therapy, to detect and avoid phage-resistant strains that can be overcome by the analysis of metadata provided by whole-genome sequencing. Here, we identified genes associated with phage resistance in 18 Acinetobacter baumannii clinical strains belonging to the ST-2 clonal complex during a decade (Ab2000 vs. 2010): 9 from 2000 to 9 from 2010. The presence of genes putatively associated with phage resistance was detected. Genes detected were associated with an abortive infection system, restriction–modification system, genes predicted to be associated with defense systems but with unknown function, and CRISPR-Cas system. Between 118 and 171 genes were found in the 18 clinical strains. On average, 26% of these genes were detected inside genomic islands in the 2000 strains and 32% in the 2010 strains. Furthermore, 38 potential CRISPR arrays in 17 of 18 of the strains were found, as well as 705 proteins associated with CRISPR-Cas systems. A moderately higher presence of these genes in the strains of 2010 in comparison with those of 2000 was found, especially those related to the restriction–modification system and CRISPR-Cas system. The presence of these genes in genomic islands at a higher rate in the strains of 2010 compared with those of 2000 was also detected. Whole-genome sequencing and bioinformatics could be powerful tools to avoid drawbacks when a personalized therapy is applied. In this study, it allows us to take care of the phage resistance in A. baumannii clinical strains to prevent a failure in possible phage therapy.
Incorporating Within-Host Diversity in Phylogenetic Analyses for Detecting Clusters of New HIV Diagnoses
Authors: Guang August , Howison Mark , Ledingham Lauren , D’Antuono Matthew , Chan Philip A. , Lawrence Charles , Dunn Casey W. , Kantor Rami
Published: February 2022

Background

Phylogenetic analyses of HIV sequences are used to detect clusters and inform public health interventions. Conventional approaches summarize within-host HIV diversity with a single consensus sequence per host of the pol gene, obtained from Sanger or next-generation sequencing (NGS). There is growing recognition that this approach discards potentially important information about within-host sequence variation, which can impact phylogenetic inference. However, whether alternative summary methods that incorporate intra-host variation impact phylogenetic inference of transmission network features is unknown.

Methods

We introduce profile sampling, a method to incorporate within-host NGS sequence diversity into phylogenetic HIV cluster inference. We compare this approach to Sanger- and NGS-derived pol and near-whole-genome consensus sequences and evaluate its potential benefits in identifying molecular clusters among all newly-HIV-diagnosed individuals over six months at the largest HIV center in Rhode Island.

Results

Profile sampling cluster inference demonstrated that within-host viral diversity impacts phylogenetic inference across individuals, and that consensus sequence approaches can obscure both magnitude and effect of these impacts. Clustering differed between Sanger- and NGS-derived consensus and profile sampling sequences, and across gene regions.

Discussion

Profile sampling can incorporate within-host HIV diversity captured by NGS into phylogenetic analyses. This additional information can improve robustness of cluster detection.
Multi-Omics Association Reveals the Effects of Intestinal Microbiome–Host Interactions on Fat Deposition in Broilers
Authors: Jing Yang , Yuan Yuqi , Monson Melissa , Wang Peng , Mu Fang , Zhang Qi , Na Wei , Zhang Ke , Wang Yuxiang , Leng Li , Li Yumao , Luan Peng , Wang Ning , Guo Rongjun , Lamont Susan J. , Li Hui , Yuan Hui
Published: February 2022

Growing evidence indicates that gut microbiota factors cannot be viewed as independent in the occurrence of obesity. Because the gut microbiome is highly dimensional and complex, studies on interactions between gut microbiome and host in obesity are still rare. To explore the relationship of gut microbiome–host interactions with obesity, we performed multi-omics associations of gut metagenome, intestinal transcriptome, and host obesity phenotypes in divergently selected obese–lean broiler lines. Metagenomic shotgun sequencing generated a total of 450 gigabases of clean data from 80 intestinal segment contents of 20 broilers (10 of each line). The microbiome comparison showed that microbial diversity and composition in the duodenum, jejunum, ileum, and ceca were altered variously between the lean- and fat-line broilers. We identified two jejunal microbes (Escherichia coliandCandidatus Acetothermia bacterium) and four cecal microbes (Alistipessp.CHKCI003,Ruminococcaceae bacterium CPB6,Clostridiales bacterium, andAnaeromassilibacillussp.An200), which were significantly different between the two lines (FDR < 0.05). When comparing functional metagenome, the fat-line broilers had an intensive microbial metabolism in the duodenum and jejunum but degenerative microbial activities in the ileum and ceca. mRNA-sequencing identified a total of 1,667 differentially expressed genes (DEG) in the four intestinal compartments between the two lines (| log2FC| > 1.5 and FDR < 0.05). Multi-omics associations showed that the 14 microbial species with abundances that were significantly related with abdominal fat relevant traits (AFRT) also have significant correlations with 155 AFRT-correlated DEG (p< 0.05). These DEG were mainly involved in lipid metabolism, immune system, transport and catabolism, and cell growth-related pathways. The present study constructed a gut microbial gene catalog of the obese–lean broiler lines. Intestinal transcriptome and metagenome comparison between the two lines identified candidate DEG and differential microbes for obesity, respectively. Multi-omics associations suggest that abdominal fat deposition may be influenced by the interactions of specific gut microbiota abundance and the expression of host genes in the intestinal compartments in which the microbes reside. Our study explored the interactions between gut microbiome and host intestinal gene expression in lean and obese broilers, which may expand knowledge on the relationships between obesity and gut microbiome.
Oral Microbiome: Streptococcus mutans/Caries Concordant-Discordant Children
Authors: Dinis Márcia , Agnello Melissa , Cen Lujia , Shokeen Bhumika , He Xuesong , Shi Wenyuan , Wong David T. W. , Lux Renate , Tran Nini Chaichanasakul
Published: February 2022

Dental caries remains the most common chronic disease in children, and the respective etiology is not fully understood. Though Streptococcus mutans is an important factor in the initiation and progression of caries, its presence is not always associated with the disease. The existence of caries discordant populations, in which S. mutans counts do not correlate with caries experience, poses a challenging problem. This study explored the possible correlation of S. mutans and other microorganism levels on caries-associated ecology of caries-concordant and discordant populations. A total of forty-seven children were analyzed in this study and stratified into four clinical groups based on their S. mutans levels in saliva (HS/LS: High/low S. mutans) and caries experience. Streptococcus mutans levels were determined by culture-based selective plating. The salivary microbiome of caries concordant and discordant populations was investigated by 16S rRNA gene sequencing and downstream bioinformatics analysis. The salivary microbial communities significantly clustered based on S. mutans levels and independent of their caries experience. In addition to S. mutans levels, significant differences in the abundance of other species were observed between HS and LS groups. Interestingly, disease-associated species such as Veillonella dispar, Streptococcus spp., and Prevotella spp. were significantly increased in HS groups and may contribute, in combination with S. mutans, to the caries progression. Furthermore, health-associated species exhibited higher abundance in the LS groups, such as Veillonella rogosae, Haemophilus sp., and Alloprevotella spp. but their possible contribution to the caries process remains to be elucidated. This study provides evidence that S. mutans may play a role in shaping the salivary microbial community. Our results highlight that future caries research should consider additional species as health/disease microbial markers in conjunction with S. mutans to improve diagnosis and caries management of the caries-discordant population.
Murine Model for Measuring Effects of Humanized-Dosing of Antibiotics on the Gut Microbiome
Authors: Leopold Shana R. , Abdelraouf Kamilia , Nicolau David P. , Agresta Hanako , Johnson Jethro , Teter Kathleen , Dunne Wm Michael , Broadwell David , van Belkum Alex , Schechter Lisa M. , Sodergren Erica J. , Weinstock George M.
Published: February 2022

There is a current need for enhancing our insight in the effects of antimicrobial treatment on the composition of human microbiota. Also, the spontaneous restoration of the microbiota after antimicrobial treatment requires better understanding. This is best addressed in well-defined animal models. We here present a model in which immune-competent or neutropenic mice were administered piperacillin-tazobactam (TZP) according to human treatment schedules. Before, during and after the TZP treatment, fecal specimens were longitudinally collected at established intervals over several weeks. Gut microbial taxonomic distribution and abundance were assessed through culture and molecular means during all periods. Non-targeted metabolomics analyses of stool samples using Quadrupole Time of Flight mass spectrometry (QTOF MS) were also applied to determine if a metabolic fingerprint correlated with antibiotic use, immune status, and microbial abundance. TZP treatment led to a 5–10-fold decrease in bacterial fecal viability counts which were not fully restored during post-antibiotic follow up. Two distinct, relatively uniform and reproducible restoration scenarios of microbiota changes were seen in post TZP-treatment mice. Post-antibiotic flora could consist of predominantly Firmicutes or, alternatively, a more diverse mix of taxa. In general, the pre-treatment microbial communities were not fully restored within the screening periods applied. A new species, closely related to Eubacterium siraeum, Mageeibacillus indolicus, and Saccharofermentans acetigenes, became predominant post-treatment in a significant proportion of mice, identified by 16S rRNA gene sequencing. Principal component analysis of QTOF MS of mouse feces successfully distinguished treated from non-treated mice as well as immunocompetent from neutropenic mice. We observe dynamic but distinct and reproducible responses in the mouse gut microbiota during and after TZP treatment and propose the current murine model as a useful tool for defining the more general post-antibiotic effects in the gastro-intestinal ecosystem where humanized antibiotic dosing may ultimately facilitate extrapolation to humans.
Genomic Insights on Variation Underlying Capsule Expression in Meningococcal Carriage Isolates From University Students, United States, 2015–2016
Authors: Whaley Melissa J. , Vuong Jeni T. , Topaz Nadav , Chang How-Yi , Thomas Jennifer Dolan , Jenkins Laurel T. , Hu Fang , Schmink Susanna , Steward-Clark Evelene , Mathis Marsenia , Rodriguez-Rivera Lorraine D. , Retchless Adam C. , Joseph Sandeep J. , Chen Alexander , Acosta Anna M. , McNamara Lucy , Soeters Heidi M. , Mbaeyi Sarah , Marjuki Henju , Wang Xin
Published: February 2022

In January and February 2015, Neisseria meningitidis serogroup B (NmB) outbreaks occurred at two universities in the United States, and mass vaccination campaigns using MenB vaccines were initiated as part of a public health response. Meningococcal carriage evaluations were conducted concurrently with vaccination campaigns at these two universities and at a third university, where no NmB outbreak occurred. Meningococcal isolates (N = 1,514) obtained from these evaluations were characterized for capsule biosynthesis by whole-genome sequencing (WGS). Functional capsule polysaccharide synthesis (cps) loci belonging to one of seven capsule genogroups (B, C, E, W, X, Y, and Z) were identified in 122 isolates (8.1%). Approximately half [732 (48.4%)] of isolates could not be genogrouped because of the lack of any serogroup-specific genes. The remaining 660 isolates (43.5%) contained serogroup-specific genes for genogroup B, C, E, W, X, Y, or Z, but had mutations in the cps loci. Identified mutations included frameshift or point mutations resulting in premature stop codons, missing or fragmented genes, or disruptions due to insertion elements. Despite these mutations, 49/660 isolates expressed capsule as observed with slide agglutination, whereas 45/122 isolates with functional cps loci did not express capsule. Neither the variable capsule expression nor the genetic variation in the cps locus was limited to a certain clonal complex, except for capsule null isolates (predominantly clonal complex 198). Most of the meningococcal carriage isolates collected from student populations at three US universities were non-groupable as a result of either being capsule null or containing mutations within the capsule locus. Several mutations inhibiting expression of the genes involved with the synthesis and transport of the capsule may be reversible, allowing the bacteria to switch between an encapsulated and non-encapsulated state. These findings are particularly important as carriage is an important component of the transmission cycle of the pathogen, and understanding the impact of genetic variations on the synthesis of capsule, a meningococcal vaccine target and an important virulence factor, may ultimately inform strategies for control and prevention of disease caused by this pathogen.
Glial Tiling in the Insect Nervous System
Authors: Pogodalla Nicole , Winkler Bente , Klämbt Christian
Published: February 2022

The Drosophila nervous system comprises a small number of well characterized glial cell classes. The outer surface of the central nervous system (CNS) is protected by a glial derived blood-brain barrier generated by perineurial and subperineurial glia. All neural stem cells and all neurons are engulfed by cortex glial cells. The inner neuropil region, that harbors all synapses and dendrites, is covered by ensheathing glia and infiltrated by astrocyte-like glial cells. All these glial cells show a tiled organization with an often remarkable plasticity where glial cells of one cell type invade the territory of the neighboring glial cell type upon its ablation. Here, we summarize the different glial tiling patterns and based on the different modes of cell-cell contacts we hypothesize that different molecular mechanisms underlie tiling of the different glial cell types.
Detection of Japanese Encephalitis by Metagenomic Next-Generation Sequencing of Cerebrospinal Fluid: A Case Report and Literature Review
Authors: Li Xin , Li Jing , Wu Guode , Wang Manxia , Jing Zhang
Published: February 2022

Japanese encephalitis (JE) is an acute viral central nervous system disease, although less than 1% of patients infected with Japanese encephalitis virus (JEV) result in JE, which has an extremely poor prognosis. The Routine detection methods for JEV are time-consuming or limited by hospital conditions, therefore, need the quicker and sensitive techniques to detect JEV. Here, we reported a 14-year-old female who was admitted to our hospital with a severe fever, progressively headache and unconsciousness. Based on the clinical presentation, Preliminary diagnosis on admission indicated central nervous system infection of suspected viral meningoencephalitis or autoimmune encephalitis. The patient's symptoms were unrelieved after being treated with empiric antiviral therapy. Magnetic resonance imaging (MRI) showed that the lesions were located in the bilateral thalamus, head of caudate nucleus, and right lenticular nucleus, so we had to consider the possibility of Flaviviruses infection. We sent the cerebrospinal fluid (CSF) for metagenomic next-generation sequencing (mNGS) immediately, subsequent result suggested the infection caused by JEV. Two days later the results of the serum agglutination test confirmed that virus immunoglobulin M antibody positive. After a week treatment with intravenous immunoglobulin (IVIG), meanwhile, the lumbar puncture was used to check the pressure and various indicators of the CSF again to evaluate the treatment effect, An decrease in the number of WBC indicates, protein and unique RNA reads that the previous experimental treatment was effective, accompany by temperature and consciousness of the patient was normalized. Two weeks after admission, the patient was transferred to the rehabilitation hospital, MR showed the lesions had disappeared completely after 2 months of follow-up. We believed that mNGS may be an effective method for rapid identification of JE.
Case Report: True Motor Recovery of Upper Limb Beyond 5 Years Post-stroke
Authors: Ciceron Carine , Sappey-Marinier Dominique , Riffo Paola , Bellaiche Soline , Kocevar Gabriel , Hannoun Salem , Stamile Claudio , Redoute Jérôme , Cotton Francois , Revol Patrice , Andre-Obadia Nathalie , Luaute Jacques , Rode Gilles
Published: February 2022

Most of motor recovery usually occurs within the first 3 months after stroke. Herein is reported a remarkable late recovery of the right upper-limb motor function after a left middle cerebral artery stroke. This recovery happened progressively, from two to 12 years post-stroke onset, and along a proximo-distal gradient, including dissociated finger movements after 5 years. Standardized clinical assessment and quantified analysis of the reach-to-grasp movement were repeated over time to characterize the recovery. Twelve years after stroke onset, diffusion tensor imaging (DTI), functional magnetic resonance imaging (fMRI), and transcranial magnetic stimulation (TMS) analyses of the corticospinal tracts were carried out to investigate the plasticity mechanisms and efferent pathways underlying motor control of the paretic hand. Clinical evaluations and quantified movement analysis argue for a true neurological recovery rather than a compensation mechanism. DTI showed a significant decrease of fractional anisotropy, associated with a severe atrophy, only in the upper part of the left corticospinal tract (CST), suggesting an alteration of the CST at the level of the infarction that is not propagated downstream. The finger opposition movement of the right paretic hand was associated with fMRI activations of a broad network including predominantly the contralateral sensorimotor areas. Motor evoked potentials were normal and the selective stimulation of the right hemisphere did not elicit any response of the ipsilateral upper limb. These findings support the idea that the motor control of the paretic hand is mediated mainly by the contralateral sensorimotor cortex and the corresponding CST, but also by a plasticity of motor-related areas in both hemispheres. To our knowledge, this is the first report of a high quality upper-limb recovery occurring more than 2 years after stroke with a genuine insight of brain plasticity mechanisms.