bluuebunny/crossref_metadata_2025 huggingface dataset:
Stem rust on barberry species in Europe: Host specificities and genetic diversity
Authors: Rodriguez-Algaba Julian , Hovmøller Mogens S. , Schulz Philipp , Hansen Jens G. , Lezáun Juan Antonio , Joaquim Jessica , Randazzo Biagio , Czembor Paweł , Zemeca Liga , Slikova Svetlana , Hanzalová Alena , Holdgate Sarah , Wilderspin Sarah , Mascher Fabio , Suffert Frederic , Leconte Marc , Flath Kerstin , Justesen Annemarie F.
Published: September 2022

The increased emergence of cereal stem rust in southern and western Europe, caused by the pathogen Puccinia graminis, and the prevalence of alternate (sexual) host, Berberis species, have regained attention as the sexual host may serve as source of novel pathogen variability that may pose a threat to cereal supply. The main objective of the present study was to investigate the functional role of Berberis species in the current epidemiological situation of cereal stem rust in Europe. Surveys in 11 European countries were carried out from 2018 to 2020, where aecial infections from five barberry species were collected. Phylogenetic analysis of 121 single aecial clusters of diverse origin using the elongation factor 1-α gene indicated the presence of different special forms (aka formae speciales) of P. graminis adapted to different cereal and grass species. Inoculation studies using aecial clusters from Spain, United Kingdom, and Switzerland resulted in 533 stem rust isolates sampled from wheat, barley, rye, and oat, which confirmed the presence of multiple special forms of P. graminis. Microsatellite marker analysis of a subset of 192 sexually-derived isolates recovered on wheat, barley and rye from the three populations confirmed the generation of novel genetic diversity revealed by the detection of 135 multilocus genotypes. Discriminant analysis of principal components resulted in four genetic clusters, which grouped at both local and country level. Here, we demonstrated that a variety of Berberis species may serve as functional alternate hosts for cereal stem rust fungi and highlights the increased risks that the sexual cycle may pose to cereal production in Europe, which calls for new initiatives within rust surveillance, epidemiological research and resistance breeding.
The immune microenvironment landscape shows treatment-specific differences in rectal cancer patients
Authors: Graham Martínez Cristina , Barella Yari , Kus Öztürk Sonay , Ansems Marleen , Gorris Mark A.J , van Vliet Shannon , Marijnen Corrie A.M , Nagtegaal Iris D
Published: September 2022

Neoadjuvant therapy is the cornerstone of modern rectal cancer treatment. Insights into the biology of tumor responses are essential for the successful implementation of organ-preserving strategies, as different treatments may lead to specific tumor responses. In this study, we aim to explore treatment-specific responses of the tumor microenvironment. Patients with locally advanced adenocarcinoma of the rectum who had received neo-adjuvant chemotherapy (CT), neo-adjuvant radiochemotherapy (RCT), neo-adjuvant radiotherapy with a long-interval (LRT) or short-interval (SRT) or no neoadjuvant therapy (NT) as control were included. Multiplex-immunofluorescence was performed to determine the presence of cytotoxic T-cells (T-cyt; CD3+CD8+), regulatory T-cells (T-reg; CD3+FOXP3+), T-helper cells (T-helper; CD3+CD8-FOXP3-), B cells (CD20+), dendritic cells (CD11c+) and tumor cells (panCK+). A total of 80 rectal cancer patients were included. Treatment groups were matched for gender, tumor location, response to therapy, and TNM stage. The pattern of response (shrinkage vs. fragmentation) was, however, different between treatment groups. Our analyses reveal that RCT-treated patients exhibited lower stromal T-helper, T-reg, and T-cyt cells compared to other treatment regimens. In conclusion, we demonstrated treatment-specific differences in the immune microenvironment landscape of rectal cancer patients. Understanding the underlying mechanisms of this landscape after a specific therapy will benefit future treatment decisions.
Excretory/secretory proteins inhibit host immune responses by downregulating the TLR4/NF-κB/MAPKs signaling pathway: A possible mechanism of immune evasion in parasitic nematode Haemonchus contortus
Authors: Wen Zhaohai , Zhang Yue , Feng Jiajun , Aimulajiang Kalibixiati , Aleem Muhammad Tahir , Lu Mingmin , Xu Lixin , Song Xiaokai , Li Xiangrui , Yan Ruofeng
Published: September 2022

Haemonchus contortus is an important parasitic nematode of ruminants. Previous studies showed that H. contortus escape the immunity through complex mechanisms, including releasing excretory/secretory proteins (ESPs) to modulate the host immune response. However, the detailed mechanism through which H. contortus excretory/secretory proteins (HcESPs) promote immune evasion remains unknown. In the present study, we demonstrated that HcESPs inhibit the adaptive immune response of goats including downregulation of immune cell antigen presentation, upregulation of immune checkpoint molecules, activation of the STAT3/PD-L1 pathway, and activation of immunosuppressive regulatory T (Treg) cells. Furthermore, HcESPs reversed the LPS-induced upregulation of pro-inflammatory mediators in PBMCs by inhibiting the TLR4/NF-κB/MAPKs/NLRP3 signaling pathway. Our study provides a better understanding of the evasion mechanisms for H. contortus, which could be helpful in providing an alternative way to prevent the infection of this parasite.
Whole-cell vaccine candidates induce a protective response against virulent Acinetobacter baumannii
Authors: Dollery Stephen J. , Zurawski Daniel V. , Bushnell Ruth V. , Tobin John K. , Wiggins Taralyn J. , MacLeod David A. , Tasker Naomi J. P. E. R. , Alamneh Yonas A. , Abu-Taleb Rania , Czintos Christine M. , Su Wanwen , Escatte Mariel G. , Meeks Heather N. , Daly Michael J. , Tobin Gregory J.
Published: September 2022

Acinetobacter baumannii causes multi-system diseases in both nosocomial settings and a pre-disposed general population. The bacterium is not only desiccation-resistant but also notoriously resistant to multiple antibiotics and drugs of last resort including carbapenem, colistin, and sulbactam. The World Health Organization has categorized carbapenem-resistant A. baumannii at the top of its critical pathogen list in a bid to direct urgent countermeasure development. Several early-stage vaccines have shown a range of efficacies in healthy mice, but no vaccine candidates have advanced into clinical trials. Herein, we report our findings that both an ionizing γ-radiation-inactivated and a non-ionizing ultraviolet C-inactivated whole-cell vaccine candidate protects neutropenic mice from pulmonary challenge with virulent AB5075, a particularly pathogenic isolate. In addition, we demonstrate that a humoral response is sufficient for this protection via the passive immunization of neutropenic mice.
MicroRNAs as diagnostic biomarkers for Tuberculosis: A systematic review and meta- analysis
Authors: Daniel Evangeline Ann , Sathiyamani Balakumaran , Thiruvengadam Kannan , Vivekanandan Sandhya , Vembuli Hemanathan , Hanna Luke Elizabeth
Published: September 2022

Background

The early diagnosis of tuberculosis using novel non-sputum-based biomarkers is of high priority in the End TB strategy. MicroRNAs (miRNAs) are significant regulators of TB pathogenesis and their differential expression pattern among healthy, latent, and active TB population has revealed their potentiality as biomarkers in recent studies. Thus, we systematically reviewed and performed a meta-analysis on the role of host miRNAs in TB diagnosis. We also reviewed the involvement of miRNAs in the immune response to Mycobacterium tuberculosis (Mtb).

Methods

Pubmed, Ovid and Cochrane databases were searched to retrieve published literature from 2000 to 2020 using predefined keywords. We screened relevant studies based on inclusion and exclusion criteria and the included studies were assessed for their quality using STARD guidelines and QUADAS-2 tool. Funnel plots were constructed to assess the publication bias. The heterogeneity of studies and overall pooled results of sensitivity, specificity and DOR were determined using forest plots.

Results

We retrieved a total of 447 studies collectively from all the databases, out of which 21 studies were included for qualitative analysis. In these studies, miR-29, miR-31, miR-125b, miR146a and miR-155 were consistently reported. The overall sensitivity, specificity and DOR of these miRNAs were found to be 87.9% (81.7-92.2), 81.2% (74.5-86.5) and 43.1(20.3-91.3) respectively. Among these, miR-31 had the maximum diagnostic accuracy, with a sensitivity of 96% (89.7-98.5), specificity of 89% (81.2-93.8) and DOR of 345.9 (90.2-1326.3), meeting the minimal target product profile (TPP) for TB diagnostics.

Conclusion

miRNAs can thus be exploited as potential biomarkers for rapid detection of tuberculosis as evident from their diagnostic performance.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021226559 PROSPERO (CRD42021226559).
Identification of four immune subtypes in locally advanced rectal cancer treated with neoadjuvant chemotherapy for predicting the efficacy of subsequent immune checkpoint blockade
Authors: He Le , Jin Min , Jian Dan , Yang Bo , Dai Nan , Feng Yan , Xiao He , Wang Dong
Published: September 2022

Introduction

Neoadjuvant chemoradiotherapy (nCRT) is the foundation treatment for locally advanced rectal cancer (LARC). The nCRT can improve the efficacy of immunotherapy because of its in situ vaccine effect.

Objective

The aim is to identify stable and reliable transcriptome signatures to predict the efficacy of immune checkpoint blockade (ICB) in patients with LARC.

Methods

Immunophenotyping was established using xCell immune cell infiltration abundance and consistent clustering in GSE39582 and verified in several data sets. The effects of immunophenotyping, follicular regulatory T cells, tumor-associated fibroblasts (CAFs), and tertiary lymphoid structure (TLS) signatures on the efficacy of ICB were analyzed using IMvigor210, GSE91061, and an independent Daping Hospital (DPH) cohort.

Results

There are four stable and repeatable immune subtypes in rectal cancer, among which C1 is a low immune infiltration type, C2 is a high interstitial infiltration type, C3 is a high immune infiltration type, and C4 is an ion channel type. C2 is mainly characterized by high infiltration of CAF. C3 is characterized by high infiltration of cytotoxic T lymphocytes, high expression of PD-L1 and TLS. In rectal cancer patients receiving nCRT, immunophenotyping was not significantly associated with pathological remission rate, but immunophenotyping was an independent prognostic factor of RFS. In IMvigor210 patients treated with atezolizumab, the pathological remission rates of C1, C2, C3, and C4 were 23.86%, 10.94%, 33.33%, and 23.08% respectively (χ2 = 8.981, P = 0.029), which were 11.76%, 50.00%, 42.86%, and 0.0% respectively in the GSE91061 patient treatment with nivolumab (Fisher’s exact probability, P = 0.018). Both follicular regulatory T cells and CAF showed a further impact on the ICB therapeutic efficacy of C2 and C3 subtypes. Additionally, both the GSE91404 and DPH cohorts showed that nCRT treatment induced a significant increase in the expression of TNFRSF9 and the abundance of macrophages in the C3 subtype.

Conclusion

Our data suggest that there are four immune types of rectal cancer, which are related to the prognosis of patients. Among them, C3 and some C2 subtypes represent the patients who may benefit from ICB after nCRT treatment.
Efficacy of immune checkpoint inhibitor therapy in EGFR mutation-positive patients with NSCLC and brain metastases who have failed EGFR-TKI therapy
Authors: Zhou Shujie , Ren Fei , Meng Xiangjiao
Published: September 2022

Background

Few treatment options are available for brain metastases (BMs) in EGFR-mutant non-small cell lung cancer (NSCLC) that progress with prior EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy. This study aimed to evaluate the efficacy of immune checkpoint inhibitor (ICI) therapy in these patients.

Methods

NSCLC patients with confirmed sensitive EGFR mutations and BMs were retrospectively reviewed. All patients experienced failure of EGFR-TKI therapy and were divided into two cohorts based on subsequent treatment. Cohort 1 included patients who received ICI therapy, while cohort 2 included patients treated with chemotherapy. Overall and intracranial objective response rates (ORRs) were used to evaluate the treatment response. Overall and intacranial progression-free survival (PFS) were calculated by Kaplan−Meier analysis and compared with the log-rank test. Univariate and multivariate Cox analyses were used to identify prognostic factors.

Results

A total of 53 patients treated with ICI therapy and 40 patients treated with chemotherapy were included in cohorts 1 and 2, respectively. In cohort 1, the overall ORR was 20.8%, with a median overall PFS of 4.2 months. The median intracranial PFS was 5.1 months. Of the 38 patients with measurable intracranial lesions, the intracranial ORR was 21.0%. Patients who received ICI combined with chemotherapy had the highest intracranial ORR of 37.5%. Compared to patients treated with chemotherapy in cohort 2, patients receiving ICI combined with chemotherapy had both longer intracranial PFS (6.4 vs. 5.1 months, p = 0.110) and overall PFS (6.2 vs. 4.6 months, p = 0.054), and these differences approached statistical significance. Univariate and multivariate Cox analyses demonstrated that high disease burden (p = 0.019), prior third-generation EGFR-TKI therapy (p = 0.019), and a poor lung immune prognostic index (LIPI) (p = 0.012) were independent negative predicators of overall PFS and that multiple BMs were negatively correlated with intracranial PFS among patients treated with ICI therapy.

Conclusions

Our results suggested that ICI combined with chemotherapy had potent intracranial efficacy and may be a promising treatment candidate in EGFR-mutant NSCLC patients with BMs for whom prior EGFR-TKI therapy failed.
Not enough by half: NFAT5 haploinsufficiency in two patients with Epstein-Barr virus susceptibility
Authors: Lopez-Rivera Daniela Olivia , Castano-Jaramillo Lina Maria , Yamazaki-Nakashimada Marco Antonio , Ramirez Uribe Rosa María Nideshda , Corcuera Delgado Celso Tomás , Ignorosa-Arellano Karen R. , Medina-Torres Edgar Alejandro , Berrón Ruiz Laura , Espinosa-Padilla Sara Elva , Scheffler-Mendoza Selma C. , López-Velázquez Gabriel , Cruz-Munoz Mario Ernesto , Lugo Reyes Saul O.
Published: September 2022

Introduction

The transcription factor Nuclear factor of activated T cells 5 (NFAT5), pivotal in immune regulation and function, can be induced by osmotic stress and tonicity-independent signals.

Objective

We aimed to investigate and characterize two unrelated patients with Epstein-Barr virus susceptibility and no known genetic etiology.

Methods

After informed consent, we reviewed the electronic charts, extracted genomic DNA, performed whole-exome sequencing, filtered, and prioritized their variants, and confirmed through Sanger sequencing, family segregation analysis, and some functional assays, including lymphoproliferation, cytotoxicity, and characterization of natural killer cells.

Results

We describe two cases of pediatric Mexican patients with rare heterozygous missense variants in NFAT5 and EBV susceptibility, a school-age girl with chronic-active infection of the liver and bowel, and a teenage boy who died of hemophagocytic lymphohistiocytosis.

Discussion

NFAT5 is an important regulator of the immune response. NFAT5 haploinsufficiency has been described as an immunodeficiency syndrome affecting both innate and adaptive immunity. EBV susceptibility might be another manifestation in the spectrum of this disease.
Screening and identification of tissue-infiltrating immune cells and genes for patients with emphysema phenotype of COPD
Authors: Wang Di , Chen Bingnan , Bai Shuang , Zhao Li
Published: September 2022

Objective

To study the tissue-infiltrating immune cells of the emphysema phenotype of chronic obstructive pulmonary disease (COPD) and find the molecular mechanism related to the development of emphysema to offer potential targets for more precise treatment of patients with COPD.

Methods

Combined analyses of COPD emphysema phenotype lung tissue-related datasets, GSE47460 and GSE1122, were performed. CIBERSORT was used to assess the distribution of tissue-infiltrating immune cells. Weighted gene co-expression network analysis (WGCNA) was used to select immune key genes closely related to clinical features. Rt-qPCR experiments were used for the validation of key genes. Emphysema risk prediction models were constructed by logistic regression analysis and a nomogram was developed.

Results

In this study, three immune cells significantly associated with clinical features of emphysema (FEV1 post-bronchodilator % predicted, GOLD Stage, and DLCO) were found. The proportion of neutrophils (p=0.025) infiltrating in the emphysema phenotype was significantly increased compared with the non-emphysema phenotype, while the proportions of M2 macrophages (p=0.004) and resting mast cells (p=0.01) were significantly decreased. Five immune-related differentially expressed genes (DEGs) were found. WGCNA and clinical lung tissue validation of patients with emphysema phenotype were performed to further screen immune-related genes closely related to clinical features. A key gene (SERPINA3) was selected and included in the emphysema risk prediction model. Compared with the traditional clinical prediction model (AUC=0.923), the combined prediction model, including SERPINA3 and resting mast cells (AUC=0.941), had better discrimination power and higher net benefit.

Conclusion

This study comprehensively analyzed the tissue-infiltrating immune cells significantly associated with emphysema phenotype, including M2 macrophages, neutrophils, and resting mast cells, and identified SERPINA3 as a key immune-related gene.
Deregulated hyaluronan metabolism in the tumor microenvironment drives cancer inflammation and tumor-associated immune suppression
Authors: Donelan William , Dominguez-Gutierrez Paul R. , Kusmartsev Sergei
Published: September 2022

Hyaluronan (HA) is known to be a prominent component of the extracellular matrix in tumors, and many solid cancers are characterized by aberrant HA metabolism resulting in increased production in tumor tissue. HA has been implicated in regulating a variety of cellular functions in tumor cells and tumor-associated stromal cells, suggesting that altered HA metabolism can influence tumor growth and malignancy at multiple levels. Importantly, increased HA production in cancer is associated with enhanced HA degradation due to high levels of expression and activity of hyaluronidases (Hyal). Understanding the complex molecular and cellular mechanisms involved in abnormal HA metabolism and catabolism in solid cancers could have important implications for the design of future cancer therapeutic approaches. It appears that extensive crosstalk between immune cells and HA-enriched stroma contributes to tumor growth and progression in several ways. Specifically, the interaction of tumor-recruited Hyal2-expressing myeloid-derived suppressor cells (MDSCs) of bone marrow origin with HA-producing cancer-associated fibroblasts and epithelial tumor cells results in enhanced HA degradation and accumulation of small pro-inflammatory HA fragments, which further drives cancer-related inflammation. In addition, hyaluronan-enriched stroma supports the transition of tumor-recruited Hyal2+MDSCs to the PD-L1+tumor-associated macrophages leading to the formation of an immunosuppressive and tolerogenic tumor microenvironment. In this review, we aim to discuss the contribution of tumor-associated HA to cancer inflammation, angiogenesis, and tumor-associated immune suppression. We also highlight the recent findings related to the enhanced HA degradation in the tumor microenvironment.
Pattern recognition receptor CD14 gene polymorphisms in alcohol use disorder patients and its Influence on liver disease susceptibility
Authors: Roy Neelanjana , Nadda Neeti , Kumar Hem , Prasad Chandreswar , Kumar Jha Jyotish , Pandey Hem Chandra , Vanamail Perumal , Saraya Anoop , Balhara Yatan Pal Singh , Shalimar  , Nayak Baibaswata
Published: September 2022

Background

Alcohol use disorders (AUDs) leading to liver disease is major concern over other spectrum of disorder. Excessive alcohol consumption resulting in leaky gut syndrome is attributed to alcohol-induced liver injury through portal translocation of bacterial endotoxin. Susceptibility to alcoholic liver disease (ALD) in AUD patients could be dependent upon genes responsible for inflammation and alcohol metabolism. The pattern recognition receptor CD14 gene is a major player in endotoxin-mediated inflammation and susceptibility to ALD. This study investigated the genetic association of CD14 polymorphisms and other mechanisms relevant to altered inflammatory responses leading to ALD.

Methods

Patients with alcohol use disorder with ALD (n = 128) and without liver disease (ALC, n = 184) and controls without alcohol use disorder (NALC, n = 152) from North India were enrolled. The CD4 gene polymorphisms in the North Indian population were evaluated by RFLP and sequencing. Secretory CD14 (sCD14), LBP, TLR4, MD2, TNFα, IL1b, IFNγ, IL6, IL10, and IL4 levels in serum were measured by ELISA among groups. The influence of polymorphisms on CD14 gene promoter activity and circulatory bacterial DNA level was determined.

Results

The CD14 gene promoter and exonic region SNPs were found to be monomorphic, except for SNP rs2569190 for the North Indian population. The genetic association of SNP rs2569190(C/T) with the risk of developing ALD was found significant for TT genotype [ORTT, 95% CI = 2.19, 1.16–4.13 for ALD vs. ALC and OR, 2.09, 1.18–3.72 for ALD vs. NALC]. An increased sCD14 level was observed in AUD patients compared to NALC control. Increased levels of LBP, TLR4, TNFα, IL1β, IFNγ, and IL6 and reduced levels of MD2, IL10, and IL4 were observed among the ALD patients compared to the other two control groups. Elevated levels of pro-inflammatory and reduced levels of anti-inflammatory cytokines were observed in the risk genotype TT groups of ALD patients and the ALC group compared to NALC. Promoter activity was observed in the intronic region flanking SNPs and risk genotype can influence reporter activity, indicating CD14 gene expression.

Conclusion

Enhanced CD14 expression associated with inflammatory responses increases susceptibility to ALD in the TT genotype of AUD patients.
Genome-wide identification of the MAPK gene family in turbot and its involvement in abiotic and biotic stress responses
Authors: Zheng Weiwei , Xu Xi-wen , E Zechen , Liu Yingjie , Chen Songlin
Published: September 2022

The mitogen-activated protein kinase (MAPK) gene family performs crucial roles in cell division, migration, development, apoptosis, inflammatory response, and abiotic and biotic stress responses. However, very little information is available about the MAPKs in turbot (Scophthalmus maximus). In this study, 15 turbot MAPKs (SmMAPKs) were identified throughout the whole genome, and their basic chemical and physical properties and subcellular localization were illustrated. All SmMAPKs contained the serine/threonine protein kinases, catalytic domain (S_TKc, SMART00220). Phylogenetic analysis revealed that SmMAPKs were classified into three subfamilies, namely, c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38. Conserved motif and gene structure analysis revealed high levels of conservation within and between phylogenetic subfamilies. Expression patterns of MAPKs in distinct tissues and under diverse abiotic and biotic stresses were examined using the published available RNA-seq data sets. As a result, SmMAPKs showed obviously tissue-specific expression. Furthermore, 7 and 10 candidate stress-responsive MAPK genes were detected under abiotic and biotic stresses, respectively, among which five common MAPK genes, namely, SmMAPK4 (ERK4), SmMAPK6 (ERK3), SmMAPK11 (p38β), SmMAPK12b (p38γ), and SmMAPK15 (ERK7/8) showed extremely significant responses to both abiotic and biotic stresses, demonstrating their potential functions in comprehensive antistress. These results demonstrate that MAPKs might play vital roles in response to various abiotic and biotic stresses in turbot, which would contribute to making scientific preventive measures to environmental changes in the process of farming and promoting the development of selective breeding for comprehensive stress resistance in turbot.
Bioregionalization of the coastal and open oceans of British Columbia and Southeast Alaska based on Sentinel-3A satellite-derived phytoplankton seasonality
Authors: Marchese Christian , Hunt Brian P. V. , Giannini Fernanda , Ehrler Matthew , Costa Maycira
Published: September 2022

Classifying the ocean into regions with distinct biogeochemical or physical properties may enhance our interpretation of ocean processes. High-resolution satellite-derived products provide valuable data to address this task. Notwithstanding, no regionalization at a regional scale has been attempted for the coastal and open oceans of British Columbia (BC) and Southeast Alaska (SEA), which host essential habitats for several ecologically, culturally, and commercially important species. Across this heterogeneous marine domain, phytoplankton are subject to dynamic ocean circulation patterns and atmosphere-ocean-land interactions, and their variability, in turn, influences marine food web structure and function. Regionalization based on phytoplankton biomass patterns along BC and SEA’s coastal and open oceans can be valuable in identifying pelagic habitats and representing a baseline for assessing future changes. We developed a two-step classification procedure, i.e., a Self-Organizing Maps (SOM) analysis followed by the affinity propagation clustering method, to define ten bioregions based on the seasonal climatology of high-resolution (300 m) Sentinel-3 surface chlorophyll-a data (a proxy for phytoplankton biomass), for the period 2016-2020. The classification procedure allowed high precision delineation of the ten bioregions, revealing separation between off-shelf bioregions and those in neritic waters. Consistent with the high-nutrient, low-chlorophyll regime, relatively low values of phytoplankton biomass (< 1 mg/m3) distinguished off-shelf bioregions, which also displayed, on average, more prominent autumn biomass peaks. In sharp contrast, neritic bioregions were highly productive (>> 1 mg/m3) and characterized by different phytoplankton dynamics. The spring phytoplankton bloom onset varied spatially and inter-annually, with substantial differences among bioregions. The proposed high-spatial-resolution regionalization constitutes a reference point for practical and more extensive implementation in understanding the spatial dynamics of the regional ecology, data-driven ocean observing systems, and objective regional management.
Genome of elegance coral Catalaphyllia jardinei (Euphylliidae)
Authors: Yu Yifei , Nong Wenyan , So Wai Lok , Xie Yichun , Yip Ho Yin , Haimovitz Jasmine , Swale Thomas , Baker David M. , Bendena William G. , Chan Ting Fung , Chui Apple P. Y. , Lau Kwok Fai , Qian Pei-Yuan , Qiu Jian-Wen , Thibodeau Benoit , Xu Fei , Hui Jerome H. L.
Published: September 2022

Coral reefs are under stress throughout the world. To better understand the molecular mechanisms underlying coral biology and their genomic evolution, here we sequenced the genome and transcriptomes of elegance coral Catalaphyllia jardinei (Euphylliidae). This monotypic genus stony coral is widespread but rare, being found across the Indo-West Pacific, from the northern Indian Ocean, Australia, Philippines, to the South China Sea. Due to its popularity among aquarium hobbyists, it is an overexploited species collected in large quantities from the wild for aquarium trade. The assembled genome is ~ 651.3 Mb in total length and of high physical contiguity with a scaffold N50 size of 28.9 Mb. The gene copy numbers of abiotic stress regulator (heat shock protein family genes) and neuropeptides (GLWamide, GRFamide, PRGamide and HIRamide) are similar to other sequenced anthozoans, and we have also identified the first set of sesquiterpenoid biosynthetic pathway genes in coral. Sequencing of small RNAs allows us to identify 35 microRNAs in C. jardinei and update the number of conserved microRNAs in cnidarians. This study established a foundation for further investigation into the roles of sesquiterpenoids and microRNAs in development of coral and understand their responses to climate change. Due to the easiness to culture C. jardinei in reef tanks and the established resources in this study, we propose this species be adopted as a new laboratory model in environmental and ecological experiments aiming to understand coral biology and responses to environmental stressors.
Dual-tracer positron emission tomography/computed tomography as an imaging probe of de novo lipogenesis in preclinical models of hepatocellular carcinoma
Authors: Tsao Chin-Ho , Jhou Rong-Hong , Ke Chien-Chih , Chang Chun-Wei , Chang Chi-Wei , Yang Bang-Hung , Huang Wen-Sheng , Shih Bing-Fu , Liu Ren-Shyan
Published: September 2022

Background

De novo lipogenesis is upregulated in many cancers, and targeting it represents a metabolic approach to cancer treatment. However, the treatment response is unpredictable because lipogenic activity varies greatly among individual tumors, thereby necessitating the assessment of lipogenic activity before treatment. Here, we proposed an imaging probe, positron emission tomography/computed tomography (PET/CT) with dual tracers combining 11C-acetate and 18F-fluorodeoxyglucose (18F-FDG), to assess the lipogenic activity of hepatocellular carcinoma (HCC) and predict the response to lipogenesis-targeted therapy.

Methods

We investigated the association between 11C-acetate/18F-FDG uptake and de novo lipogenesis in three HCC cell lines (from well-differentiated to poorly differentiated: HepG2, Hep3B, and SkHep1) by examining the expression of lipogenic enzymes: acetyl-CoA synthetase 2 (ACSS2), fatty acid synthase (FASN), and ATP citrate lyase (ACLY). The glycolysis level was determined through glycolytic enzymes: pyruvate dehydrogenase expression (PDH). On the basis of the findings of dual-tracer PET/CT, we evaluated the treatment response to a lipase inhibitor (orlistat) in cell culture experiments and xenograft mice.

Results

Dual-tracer PET/CT revealed the lipogenic activity of various HCC cells, which was positively associated with 11C-acetate uptake and negatively associated with 18F-FDG uptake. This finding represents the negative association between 11C-acetate and 18F-FDG uptake. Because these two tracers revealed the lipogenic and glycolytic activity, respectively, which implies an antagonism between lipogenic metabolism and glucose metabolism in HCC. In addition, dual-tracer PET/CT not only revealed the lipogenic activity but also predicted the treatment response to lipogenesis-targeted therapy. For example, HepG2 xenografts with high 11C-acetate but low 18F-FDG uptake exhibited high lipogenic activity and responded well to orlistat treatment, whereas SkHep1 xenografts with low 11C-acetate but high 18F-FDG uptake exhibited lower lipogenic activity and poor response to orlistat.

Conclusion

The proposed non-invasive dual-tracer PET/CT imaging can reveal the lipogenesis and glycolysis status of HCC, thus providing an ideal imaging probe for predicting the therapeutic response of HCC to lipogenesis-targeted therapy.
Case report: Optical coherence tomography for monitoring biologic therapy in psoriasis and atopic dermatitis
Authors: Ha-Wissel Linh , Yasak Handan , Huber Robert , Zillikens Detlef , Ludwig Ralf J. , Thaçi Diamant , Hundt Jennifer E.
Published: September 2022

Biologic therapies are increasingly used to treat chronic inflammatory skin diseases such as psoriasis and atopic dermatitis. In clinical practice, scores based on evaluation of objective and subjective symptoms are used to assess disease severity, leading to evaluation of treatment goals with clinical decisions on treatment initiation, switch to another treatment modality or to discontinue current treatment. However, this visual-based scoring is relatively subjective and inaccurate due to inter- and intraobserver reliability. Optical coherence tomography (OCT) is a fast, high-resolution, in vivo imaging modality that enables the visualization of skin structure and vasculature. We evaluated the use of OCT for quantification and monitoring of skin inflammation to improve objective assessment of disease activity in patients with psoriasis and atopic dermatitis. We assessed the following imaging parameters including epidermal thickness, vascular density, plexus depth, vessel diameter, and vessel count. A total of four patients with psoriasis or atopic dermatitis were treated with biologic agents according to current treatment guidelines. OCT was used to monitor their individual treatment response in a target lesion representing disease activity for 52 weeks. Psoriatic and eczema lesions exhibited higher epidermal thickness, increased vascular density, and higher vessel count compared to uninvolved skin. An upward shift of the superficial vascular plexus accompanied by smaller vessel diameters was seen in psoriasis in contrast to atopic dermatitis, where larger vessels were observed. A response to biologic therapy was characterized by normalization of the imaging parameters in the target lesions in comparison to uninvolved skin during the observation period of 52 weeks. Optical coherence tomography potentially serves as an instrument to monitor biologic therapy in inflammatory skin diseases. Imaging parameters may enable objective quantification of inflammation in psoriasis or atopic dermatitis in selected representative skin areas. OCT may reveal persistent subclinical inflammation in atopic dermatitis beyond clinical remission.
A computational model for microbial colonization of an antifouling surface
Authors: Sinclair Patrick , Longyear Jennifer , Reynolds Kevin , Finnie Alistair A. , Brackley Chris A. , Carballo-Pacheco Martín , Allen Rosalind J.
Published: September 2022

Biofouling of marine surfaces such as ship hulls is a major industrial problem. Antifouling (AF) paints delay the onset of biofouling by releasing biocidal chemicals. We present a computational model for microbial colonization of a biocide-releasing AF surface. Our model accounts for random arrival from the ocean of microorganisms with different biocide resistance levels, biocide-dependent proliferation or killing, and a transition to a biofilm state. Our computer simulations support a picture in which biocide-resistant microorganisms initially form a loosely attached layer that eventually transitions to a growing biofilm. Once the growing biofilm is established, immigrating microorganisms are shielded from the biocide, allowing more biocide-susceptible strains to proliferate. In our model, colonization of the AF surface is highly stochastic. The waiting time before the biofilm establishes is exponentially distributed, suggesting a Poisson process. The waiting time depends exponentially on both the concentration of biocide at the surface and the rate of arrival of resistant microorganisms from the ocean. Taken together our results suggest that biofouling of AF surfaces may be intrinsically stochastic and hence unpredictable, but immigration of more biocide-resistant species, as well as the biological transition to biofilm physiology, may be important factors controlling the time to biofilm establishment.
The complete mitochondrial genome of Isochrysis galbana harbors a unique repeat structure and a specific trans-spliced cox1 gene
Authors: Fang Jingping , Xu Xiuming , Chen Qinchang , Lin Aiting , Lin Shaoqing , Lei Wen , Zhong Cairong , Huang Yongji , He Yongjin
Published: September 2022

The haptophyte Isochrysis galbana is considered as a promising source for food supplements due to its rich fucoxanthin and polyunsaturated fatty acids content. Here, the I. galbana mitochondrial genome (mitogenome) was sequenced using a combination of Illumina and PacBio sequencing platforms. This 39,258 bp circular mitogenome has a total of 46 genes, including 20 protein-coding genes, 24 tRNA genes and two rRNA genes. A large block of repeats (~12.7 kb) was segregated in one region of the mitogenome, accounting for almost one third of the total size. A trans-spliced gene cox1 was first identified in I. galbana mitogenome and was verified by RNA-seq and DNA-seq data. The massive expansion of tandem repeat size and cis- to trans-splicing shift could be explained by the high mitogenome rearrangement rates in haptophytes. Strict SNP calling based on deep transcriptome sequencing data suggested the lack of RNA editing in both organelles in this species, consistent with previous studies in other algal lineages. To gain insight into haptophyte mitogenome evolution, a comparative analysis of mitogenomes within haptophytes and among eight main algal lineages was performed. A core gene set of 15 energy and metabolism genes is present in haptophyte mitogenomes, consisting of 1 cob, 3 cox, 7 nad, 2 atp and 2 ribosomal genes. Gene content and order was poorly conserved in this lineage. Haptophyte mitogenomes have lost many functional genes found in many other eukaryotes including rps/rpl, sdh, tat, secY genes, which make it contain the smallest gene set among all algal taxa. All these implied the rapid-evolving and more recently evolved mitogenomes of haptophytes compared to other algal lineages. The phylogenetic tree constructed by cox1 genes of 204 algal mitogenomes yielded well-resolved internal relationships, providing new evidence for red-lineages that contained plastids of red algal secondary endosymbiotic origin. This newly assembled mitogenome will add to our knowledge of general trends in algal mitogenome evolution within haptophytes and among different algal taxa.
Mixed conifer-broadleaf trees on arbuscular mycorrhizal and ectomycorrhizal communities in rhizosphere soil of different plantation stands in the temperate zone, Northeast China
Authors: Zhang Yong , Wang Qingcheng , Xu Liqing , Ma Shuangjiao , Cui Donghai , Zhu Kaiyue , Feng Wanju
Published: September 2022

In comparison with ectomycorrhizal (EM) tree species, arbuscular mycorrhizal (AM) trees have different litter quality and nitrogen cycle modes, which may affect mycorrhizal colonization and the community composition and diversity. However, available studies addressing the mycorrhizal fungal colonization rate, diversity and community composition in mixed forest stands composed of AM and EM trees are rare. In the present study, we assessed litter quality, soil physicochemical properties and correlated them with mycorrhizal community characteristics in rhizosphere soils of monoculture and mixture plantation stands of AM tree species (Fraxinus mandschurica Rupr.) and EM tree species (Larix gmelinii Rupr., Picea koraiensis Nakai) in Northeast China. We hypothesized that (1) the effect of mixture pattern on mycorrhizal colonization rate and diversity would change with tree species, (2) the effect of mixture pattern on mycorrhizal community composition would be less pronounced in comparison with that of tree species. We found that mixture did not change AMF colonization rate regardless of mixture identity, whereas mixture and tree species exerted significant effects on EMF colonization rate. For AMF community, both M-AS (Fraxinus mandschurica Rupr. and Picea koraiensis Nakai) and M-AL (Fraxinus mandschurica Rupr. and Larix gmelinii Rupr.) mixtures significantly increased Pielou index and Simpson index, whereas only M-AS significantly increased Sobs. For EMF community, mixture significantly affected examined diversity indices except for Chao1. Mixture significantly shifted AMF and EMF community, and the magnitude was tree species dependent. The dominant genera in AMF and EMF communities in plantation stands were Glomus and Tomentella, respectively. The EnvFit analysis showed that the determinant factors of EMF community are soil moisture, pH, nitrate nitrogen content, dissolved organic nitrogen content, soil organic matter content, soil organic carbon/total nitrogen and litter carbon/total nitrogen. In conclusion, mixed conifer-broadleaf trees significantly changed soil physicochemical properties, litter quality as well as mycorrhizal fungi community diversity and composition.
Efficacy of obstructive sleep apnea treatment by antileukotriene receptor and surgery therapy in children with adenotonsillar hypertrophy: A descriptive and cohort study
Authors: Tran-Minh Dien , Phi-Thi-Quynh Anh , Nguyen-Dinh Phuc , Duong-Quy Sy
Published: September 2022

Background

Prevalence of obstructive sleep apnea (OSA) in children with adenotonsillar hypertrophy is high and related to the occlusion of the upper airway. The main treatments of OSA in these children is adenotonsillectomy. However, this intervention is an invasive method with a various success rate. Thus, the indications of tonsillectomy remain debatable and non-invasive treatment is still a potential choice in these patients.

Methods

It was a cross-sectional and interventional study. This study included children aged from 2 to 12 years-old who were diagnosed with OSA by respiratory polygraphy and had tonsillar hypertrophy with/without adenoid hypertrophy. All main data including age, gender, height, weight, body mass index (BMI), clinical symptoms, and medical history were recorded for analysis. Physical examination and endoscopy were done to evaluate the size of tonsillar and adenoid hypertrophy by using Brodsky and Likert classifications, respectively. The severity of OSA was done by using the classification of AHI severity for children.

Results

There were 114 patients (2–12 years old) with a mean age of 5.5 ± 2.1 years included in the present study. The main reasons for consultations were snoring (96.7%), a pause of breathing (57.1%), an effort to breathe (36.8%), unrefreshing sleep (32%), doziness (28.2%), and hyperactivity (26.3%). There were 36% of subjects with tonsillar hypertrophy grade 1–2, 48.2% with grade 3, and 15.8% with grade 4 (Brodsky classification); among them, there were 46.5% of subjects with grades 1–2 of adenoid hypertrophy, 45.6% with grade 3, and 7.0% with grade 4 (Likert classification). The mean AHI was 12.6 ± 11.2 event/h. There was a significant correlation between the mean AHI and the level of tonsillar and adenoid hypertrophy severity (r = 0.7601 and r = 0.7903; p < 0.05 and p < 0.05, respectively). The improvement of clinical symptoms of study subjects was found in both groups treated with ALR (antileukotriene receptor) or ST (surgery therapy). The symptoms related to OSA at night including snoring, struggle to breathe, sleeping with the mouth open, and stopping breathing during sleep were significantly improved after treatment with ATR and with ST (p < 0.001 and p = 0.001, respectively). The mean AHI was significantly reduced in comparison with before treatment in study subjects treated with ALR (0.9 ± 1.0 vs. 3.9 ± 2.7 events/h; p = 0.001) or with ST (3.5 ± 1.4 vs. 23.4 ± 13.1 events/h; p < 0.001).

Conclusion

The treatment of OSA due to adeno-tonsillar hypertrophy with ALR for moderate OSA or surgery for severe OSA might reduce the symptoms related to OSA at night and during the day.
Inclusion body myositis: Update on the diagnostic and therapeutic landscape
Authors: Naddaf Elie
Published: September 2022

Inclusion body myositis (IBM) is a progressive muscle disease affecting patients over the age of 40, with distinctive clinical and histopathological features. The typical clinical phenotype is characterized by prominent involvement of deep finger flexors and quadriceps muscles. Less common presentations include isolated dysphagia, asymptomatic hyper-CKemia, and axial or limb weakness beyond the typical pattern. IBM is associated with marked morbidity as majority of patients eventually become wheelchair dependent with limited use of their hands and marked dysphagia. Furthermore, IBM mildly affects longevity with aspiration pneumonia and respiratory complications being the most common cause of death. On muscle biopsy, IBM is characterized by a peculiar combination of endomysial inflammation, rimmed vacuoles, and protein aggregation. These histopathological features are reflective of the complexity of underlying disease mechanisms. No pharmacological treatment is yet available for IBM. Monitoring for swallowing and respiratory complications, exercise, and addressing mobility issues are the mainstay of management. Further research is needed to better understand disease pathogenesis and identify novel therapeutic targets.
Nomogram based on clinical and brain computed tomography characteristics for predicting more than 5 cerebral microbleeds in the hypertensive population
Authors: Wang Xin-Bin , Dong Hao , Qiu Yong-Gang , Lou Cun-Cheng , Huang De-Yun , Zhang Jing , Chen Di-Hong , Feng Han , Fang Xu
Published: September 2022

Background

Cerebral microbleeds (CMBs) are common in the hypertensive population and can only be detected with magnetic resonance imaging (MRI). The anticoagulation and thrombolytic regimens for patients with >5 CMBs are different from those for patients with ≤ 5 CMBs. However, MRI is not suitable for evaluating CMBs in patients with MRI contraindications or acute ischemic stroke urgently requiring thrombolysis. We aimed to develop and validate a nomogram combining clinical and brain computed tomography (CT) characteristics for predicting >5 CMBs in a hypertensive population.

Materials and methods

In total, 160 hypertensive patients from 2016 to 2020 who were confirmed by MRI to have >5 (77 patients) and ≤ 5 CMBs (83) were retrospectively analyzed as the training cohort. Sixty-four hypertensive patients from January 2021 to February 2022 were included in the validation cohort. Multivariate logistic regression was used to evaluate >5 CMBs. A combined nomogram was constructed based on the results, while clinical and CT models were established according to the corresponding characteristics. Receiver operating characteristic (ROC) and calibration curves and decision curve analysis (DCA) were used to verify the models.

Results

In the multivariable analysis, the duration of hypertension, level of homocysteine, the number of lacunar infarcts (LIs), and leukoaraiosis (LA) score were included as factors associated with >5 CMBs. The clinical model consisted of the duration of hypertension and level of homocysteine, while the CT model consisted of the number of LIs and LA. The combined model consisted of the duration of hypertension, level of homocysteine, LI, and LA. The combined model achieved an area under the curve (AUC) of 0.915 (95% confidence interval [CI]: 0.860–0.953) with the training cohort and 0.887 (95% CI: 0.783–0.953) with the validation cohort, which were higher than those of the clinical model [training cohort: AUC, 0.797 (95% CI: 0.726, 0.857); validation cohort: AUC, 0.812 (95% CI: 0.695, 0.899)] and CT model [training cohort: AUC, 0.884 (95% CI: 0.824, 0.929); validation cohort: AUC, 0.868 (95% CI: 0.760, 0.940)]. DCA showed that the clinical value of the combined model was superior to that of the clinical model and CT model.

Conclusion

A combined model based on clinical and CT characteristics showed good diagnostic performance for predicting >5 CMBs in hypertensive patients.