bluuebunny/crossref_metadata_2025 huggingface dataset:
Building school leaders’ instructional leadership capacity through virtual professional leadership learning communities
Authors: Pashmforoosh Roya , Irby Beverly J. , Lara-Alecio Rafael , Tong Fuhui
Published: April 2023

Introduction

Research is still emerging on how to develop school leaders’ instructional capacity. We implemented research-based practices through virtual professional leadership learning communities (VPLCs) for building school leaders’ instructional capacity. We examined school leaders’ perceptions of (a) the effectiveness of the VPLC as a vehicle for improving instructional practices, (b) the essential components of an effective VPLC, and (c) school leaders’ instructional leadership practices through discussions within VPLC.

Methods

The participants of this study were 40 school leaders at the principal and assistant principal levels in elementary schools in the state of Texas. Based on the research purpose and design, multiple types of data were collected to explore participants’ perceptions and experiences of VPLC.

Results

Based on both qualitative and quantitative analyses of the data from questionnaires and interviews, we found that this VPLC allowed participants to share leadership research and resources and provided them with an avenue for collaborating and communicating with other school leaders. The results of the qualitative data revealed two major components that the participants thought a VPLC should provide based on their experiences in the program (a) community building through collaboration and (b) reflective modules and discussion.

Discussion

An SST explanation can potentially reduce some aspects of homophobia among both healthcare professionals and lay people. Also, worryingly, Chinese healthcare professionals, especially medical professionals, reported more homophobia than lay individuals These VPLCs were regarded as grounds for innovation, as participants worked together with other school leaders to find problems and determine creative and workable solutions focused on building instructional capacity in serving high-needs schools. Thus, school leaders can be supported through sustained, effective professional learning in communities of practice, or virtual professional leadership learning communities.
Surgical strategies of complicated pheochromocytomas/paragangliomas and literature review
Authors: Wang Xu , Zhao Yang , Liao Zhangcheng , Zhang Yushi
Published: April 2023

Pheochromocytomas (PCC)/paragangliomas (PGL) are catecholamine (CA) -secreting neuroendocrine tumors, which are known as PPGL due to their histological and pathophysiological similarities. In addition to the typical triad of paroxysmal headache, palpitation, and sweating, PPGL may also be accompanied by symptoms and signs involving multiple organs and systems such as the cardiovascular system, digestive system, endocrine system, and nervous system. Currently, surgical resection is the first choice for PPGL. Safe and effective surgical management of complicated PPGL is the goal of clinical work. In this paper, we discuss this hot issue based on complicated PPGL cases, aiming to share our experience of the surgical management strategy of PPGL.
Low rectus femoris mass index is closely associated with diabetic peripheral neuropathy
Authors: Wang Lina , Lin Xiaopu , Huang Haishan , Wang Yanfang , Liang Xinxin , Zheng Xiaobin , Xu Lingling
Published: April 2023

Aims

To assess the association of rectus femoris mass index (RFMI) with diabetic peripheral neuropathy (DPN) in individuals with type 2 diabetes mellitus (T2DM).

Methods

Totally 948 T2DM cases were enrolled. Nerve conduction parameters, quantitative sensory threshold and rectus femoris cross-sectional area (RFCSA) were obtained, and rectus femoris mass index (RFMI=RFCSA/height2) was derived. The patients were assigned to four groups based on interquartile spacing of RFMI.

Results

Motor/sensory nerve amplitude and conduction velocity (CV) were significantly lower in the low-level RFMI groups (all P<0.05). RFMI was positively associated with mean motor/sensory nerve amplitude and CV (both P<0.05). T2DM duration above 10 years and RFMI below 2.37cm²/m² had significant associations with DPN (both P<0.001). Receiver operating characteristic (ROC) curve analysis demonstrated cutoffs for T2DM duration and RFMI of 7 years and 2.2 cm²/m², respectively (AUC=0.75, 95% CI: 0.72-0.79; sensitivity, 68.4%; specificity, 66.8%).

Conclusion

DPN is significantly associated with reduced RFMI in T2DM patients. Decreased muscle mass seems to be associated with motor/sensory nerve amplitude and CV. RFMI combined with T2DM duration may represent a potent tool for predicting DPN occurrence in T2DM cases.

Clinical trial registration

http://www.chictr.org.cn, identifier ChiCTR2100049150.
Association between different metabolic phenotypes of obesity and thyroid disorders among Chinese adults: a nationwide cross-sectional study
Authors: Song Bo , Lu Cihang , Teng Di , Shan Zhongyan , Teng Weiping
Published: April 2023

Background

Increased body mass index (BMI) and metabolic abnormalities both have potential associations with thyroid disease. The aim of this study was to investigate the correlation between different metabolic phenotypes of obesity and thyroid disorders using nationwide data from China.

Methods

Data were collected from a cross-sectional survey called the Thyroid Disorders, Iodine Status, and Diabetes Epidemiological Survey conducted between 2015 and 2017 in China. A total of 69007 subjects aged 18 years or older were defined and divided into six groups on the basis of BMI and metabolic health status: metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy overweight (MHOW), metabolically unhealthy overweight (MUOW), metabolically healthy obesity (MHO), and metabolically unhealthy obesity (MUO). We estimated the odds ratios (ORs) and confidence intervals [CIs] for different thyroid disorders according to metabolic phenotypes using multivariate logistic regression models.

Results

In our study, we found that the prevalence of subclinical hypothyroidism was almost as high in the MUNW group as in the MUO group, the prevalence of overt hyperthyroidism was highest in the MUNW group and Graves’ disease was highest in the MHO group. Our results also suggested that the prevalence of goiter and thyroid nodules increased with increased BMI values and that the MUO group had the highest incidence. Multivariate logistic regression analysis indicated that subjects with unhealthy metabolic phenotypes (MUNW, MUOW, and MUO) all had an increased risk of subclinical hypothyroidism, regardless of their BMI. MUNW subjects had an approximately 1.6-fold higher risk of overt hyperthyroidism and a 1.8-fold higher risk of Graves’ disease than their metabolically healthy counterparts (MHNW). The present study also demonstrated that the MUO group had the highest risk of goiter and thyroid nodules among the metabolic phenotypes of obesity.

Conclusion

Based on our study, we found that metabolic abnormalities and obesity play different roles in various thyroid diseases. Metabolically unhealthy individuals, both with and without obesity, have a higher risk of thyroid disorders than metabolically healthy individuals without obesity.
Obesity and type 2 diabetes mellitus: connections in epidemiology, pathogenesis, and treatments
Authors: Ruze Rexiati , Liu Tiantong , Zou Xi , Song Jianlu , Chen Yuan , Xu Ruiyuan , Yin Xinpeng , Xu Qiang
Published: April 2023

The prevalence of obesity and diabetes mellitus (DM) has been consistently increasing worldwide. Sharing powerful genetic and environmental features in their pathogenesis, obesity amplifies the impact of genetic susceptibility and environmental factors on DM. The ectopic expansion of adipose tissue and excessive accumulation of certain nutrients and metabolites sabotage the metabolic balance via insulin resistance, dysfunctional autophagy, and microbiome-gut-brain axis, further exacerbating the dysregulation of immunometabolism through low-grade systemic inflammation, leading to an accelerated loss of functional β-cells and gradual elevation of blood glucose. Given these intricate connections, most available treatments of obesity and type 2 DM (T2DM) have a mutual effect on each other. For example, anti-obesity drugs can be anti-diabetic to some extent, and some anti-diabetic medicines, in contrast, have been shown to increase body weight, such as insulin. Meanwhile, surgical procedures, especially bariatric surgery, are more effective for both obesity and T2DM. Besides guaranteeing the availability and accessibility of all the available diagnostic and therapeutic tools, more clinical and experimental investigations on the pathogenesis of these two diseases are warranted to improve the efficacy and safety of the available and newly developed treatments.
The interplay of sex steroid hormones and microRNAs in endometrial cancer: current understanding and future directions
Authors: Thakur Lovlesh , Thakur Sunil
Published: April 2023

Introduction

Endometrial cancer is a hormone-dependent malignancy, and sex steroid hormones play a crucial role in its pathogenesis. Recent studies have demonstrated that microRNAs (miRNAs) can regulate the expression of sex steroid hormone receptors and modulate hormone signaling pathways. Our aim is to provide an overview of the current understanding of the role of miRNAs in endometrial cancer regulated by sex steroid hormone pathways.

Methods

A thorough literature search was carried out in the PubMed database. The articles published from 2018 to the present were included. Keywords related to miRNAs, endometrial cancer, and sex steroid hormones were used in the search.

Results

Dysregulation of miRNAs has been linked to abnormal sex steroid hormone signaling and the development of endometrial cancer. Various miRNAs have been identified as modulators of estrogen and progesterone receptor expression, and the miRNA expression profile has been shown to be a predictor of response to hormone therapy. Additionally, specific miRNAs have been implicated in the regulation of genes involved in hormone-related signaling pathways, such as the PI3K/Akt/mTOR and MAPK/ERK pathways.

Conclusion

The regulation of sex steroid hormones by miRNAs is a promising area of research in endometrial cancer. Future studies should focus on elucidating the functional roles of specific miRNAs in sex steroid hormone signaling and identifying novel miRNA targets for hormone therapy in endometrial cancer management.
3DCNN landslide susceptibility considering spatial-factor features
Authors: Liu Mengmeng , Liu Jiping , Xu Shenghua , Chen Cai , Bao Shuai , Wang Zhuolu , Du Jun
Published: April 2023

Effective landslide disaster risk management contributes to sustainable development. A useful method for emergency management and landslide avoidance is Landslide Susceptibility Mapping (LSM). The statistical landslide susceptibility prediction model based on slope unit ignores the re-lationship between landslide triggering factors and spatial characteristics. It disregards the influence of adjacent image elements around the slope-unit element. Therefore, this paper proposes a hardwired kernels-3DCNN approach to LSMs considering spatial-factor features. This method effectively solved the problem of low dimensionality of 3D convolution in the hazard factor layer by combining Prewitt operators to enhance the generation of multi-level 3D cube input data sets. The susceptibility value of the target area was then calculated using a 3D convolution to extract spatial and multi-factor features between them. A geospatial dataset of 402 landslides in Xiangxi Tujia and Miao Autonomous Prefecture, Hunan Province, China, was created for this study. Nine landslide trigger factors, including topography and geomorphology, stratigraphic lithology, rainfall, and human influences, were employed in the LSM. The research area’s pixel points’ landslide probabilities were then estimated by the training model, yielding the sensitivity maps. According to the results of this study, the 3DCNN model performs better when spatial information are included and trigger variables are taken into account, as shown by the high values of the area under the receiver operating characteristic curve (AUC) and other quantitative metrics. The proposed model outperforms CNN and SVM in AUC by 4.3% and 5.9%, respectively. Thus, the 3DCNN model, with the addition of spatial attributes, effectively improves the prediction accuracy of LSM. At the same time, this paper found that the model performance of the proposed method is related to the actual space size of the landslide body by comparing the impact of input data of different scales on the proposed method.
Transcriptomic insights into adenoid cystic carcinoma via RNA sequencing
Authors: Tang Yu-Fang , An Pu-Gen , Gu Bao-Xin , Yi Shu , Hu Xiao , Wu Wen-Jie , Zhang Jie
Published: April 2023

Background: The aim of this study was to investigate the underlying mechanisms of adenoid cystic carcinoma (ACC) at the transcriptome level.

Materials and methods: We obtained paired tumor and normal salivary gland tissues from 15 ACC patients, which were prepared for RNA sequencing.

Results: Gene enrichment analysis revealed that the upregulated pathways were mainly involved in axonogenesis, and the downregulated pathways were mainly related to leukocyte migration, the adaptive immune response, lymphocyte-mediated immunity, and the humoral immune response. T-cells, B-cells and NK cells showed low infiltration in ACC tissues. In addition to the gene fusions MYB-NFIB and MYBL1-NFIB, a new gene fusion, TVP23C-CDRT4, was also detected in 3 ACC tissues. PRAME was significantly upregulated in ACC tissues, while antigen-presenting human leukocyte antigen (HLA) genes were downregulated.

Conclusion: We found a new gene fusion, TVP23C-CDRT4, that was highly expressed in ACC. PRAME may be an attractive target for ACC immunotherapy.
ONT long-read WGS for variant discovery and orthogonal confirmation of short read WGS derived genetic variants in clinical genetic testing
Authors: Kaplun Ludmila , Krautz-Peterson Greice , Neerman Nir , Stanley Christine , Hussey Shane , Folwick Margo , McGarry Ava , Weiss Shirel , Kaplun Alexander
Published: April 2023

Technological advances in Next-Generation Sequencing dramatically increased clinical efficiency of genetic testing, allowing detection of a wide variety of variants, from single nucleotide events to large structural aberrations. Whole Genome Sequencing (WGS) has allowed exploration of areas of the genome that might not have been targeted by other approaches, such as intergenic regions. A single technique detecting all genetic variants at once is intended to expedite the diagnostic process while making it more comprehensive and efficient. Nevertheless, there are still several shortcomings that cannot be effectively addressed by short read sequencing, such as determination of the precise size of short tandem repeat (STR) expansions, phasing of potentially compound recessive variants, resolution of some structural variants and exact determination of their boundaries, etc. Therefore, in some cases variants can only be tentatively detected by short reads sequencing and require orthogonal confirmation, particularly for clinical reporting purposes. Moreover, certain regulatory authorities, for example, New York state CLIA, require orthogonal confirmation of every reportable variant. Such orthogonal confirmations often involve numerous different techniques, not necessarily available in the same laboratory and not always performed in an expedited manner, thus negating the advantages of “one-technique-for-all” approach, and making the process lengthy, prone to logistical and analytical faults, and financially inefficient. Fortunately, those weak spots of short read sequencing can be compensated by long read technology that have comparable or better detection of some types of variants while lacking the mentioned above limitations of short read sequencing. At Variantyx we have developed an integrated clinical genetic testing approach, augmenting short read WGS-based variant detection with Oxford Nanopore Technologies (ONT) long read sequencing, providing simultaneous orthogonal confirmation of all types of variants with the additional benefit of improved identification of exact size and position of the detected aberrations. The validation study of this augmented test has demonstrated that Oxford Nanopore Technologies sequencing can efficiently verify multiple types of reportable variants, thus ensuring highly reliable detection and a quick turnaround time for WGS-based clinical genetic testing.
The narrative practices of hostile environments: the story of the nation-as-family and the story of security
Authors: Whittle Matthew
Published: April 2023

This article contributes to research into the importance of storytelling in asylum practice by examining the narratives used to promote and justify Hostile Environment policies. The two narrative practices identified are the “story of the nation-as-family”, which defines national belonging predominantly by markers of race and ethnicity, and the “story of security”, whereby racialized refugees are framed as potential threats to the nation's socio-economic stability. The former propagates a notion of consanguinity that works to exclude and silence people seeking asylum from non-European nations. The latter sees the rhetoric of a “clash of civilisations” so central to the “War on Terror” taken up in policy debates about climate-induced migration. An analysis of the way in which these stories are staged and critiqued in the writing of Abdulrazak Gurnah and Stephen Collis reveals how they elide the relationship between forced migration and the history of European colonialism. In exploring this elision, this article insists on the significance of literary texts as spaces where monocultural conceptions of belonging can be confronted, and where understanding Europe's colonial past is established as an integral part of hearing the stories of refugees in the present.
American ginseng with different processing methods ameliorate immunosuppression induced by cyclophosphamide in mice via the MAPK signaling pathways
Authors: Zhang Yan-Ting , Tian Wei , Lu Yu-Shun , Li Zhi-Man , Ren Duo-Duo , Zhang Yue , Sha Ji-Yue , Huo Xiao-Hui , Li Shan-Shan , Sun Yin-Shi
Published: April 2023

This study aimed to clarify the effects of two processed forms of American ginseng (Panax quinquefolius L.) on immunosuppression caused by cyclophosphamide (CTX) in mice. In the CTX-induced immunosuppressive model, mice were given either steamed American ginseng (American ginseng red, AGR) or raw American ginseng (American ginseng soft branch, AGS) by intragastric administration. Serum and spleen tissues were collected, and the pathological changes in mice spleens were observed by conventional HE staining. The expression levels of cytokines were detected by ELISA, and the apoptosis of splenic cells was determined by western blotting. The results showed that AGR and AGS could relieve CTX-induced immunosuppression through the enhanced immune organ index, improved cell-mediated immune response, increased serum levels of cytokines (TNF-α, IFN-γ, and IL-2) and immunoglobulins (IgG, IgA, and IgM), as well as macrophage activities including carbon clearance and phagocytic index. AGR and AGS downregulated the expression of BAX and elevated the expression of Bcl-2, p-P38, p-JNK, and p-ERK in the spleens of CTX-injected animals. Compared to AGS, AGR significantly improved the number of CD4+CD8-T lymphocytes, the spleen index, and serum levels of IgA, IgG, TNF-α, and IFN-γ. The expression of the ERK/MAPK pathway was markedly increased. These findings support the hypothesis that AGR and AGS are effective immunomodulatory agents capable of preventing immune system hypofunction. Future research may investigate the exact mechanism to rule out any unforeseen effects of AGR and AGS.
G protein-coupled receptor 183 mediates the sensitization of Burkitt lymphoma tumors to CD47 immune checkpoint blockade by anti-CD20/PI3Kδi dual therapy
Authors: Ribeiro Marcelo Lima , Profitós-Pelejà Núria , Santos Juliana Carvalho , Blecua Pedro , Reyes-Garau Diana , Armengol Marc , Fernández-Serrano Miranda , Miskin Hari P. , Bosch Francesc , Esteller Manel , Normant Emmanuel , Roué Gael
Published: April 2023

Background

Immunotherapy-based regimens have considerably improved the survival rate of B-cell non-Hodgkin lymphoma (B-NHL) patients in the last decades; however, most disease subtypes remain almost incurable. TG-1801, a bispecific antibody that targets CD47 selectively on CD19+ B-cells, is under clinical evaluation in relapsed/refractory (R/R) B-NHL patients either as a single-agent or in combination with ublituximab, a new generation CD20 antibody.

Methods

A set of eight B-NHL cell lines and primary samples were cultured in vitro in the presence of bone marrow-derived stromal cells, M2-polarized primary macrophages, and primary circulating PBMCs as a source of effector cells. Cell response to TG-1801 alone or combined with the U2 regimen associating ublituximab to the PI3Kδ inhibitor umbralisib, was analyzed by proliferation assay, western blot, transcriptomic analysis (qPCR array and RNA sequencing followed by gene set enrichment analysis) and/or quantification of antibody-dependent cell death (ADCC) and antibody-dependent cell phagocytosis (ADCP). CRISPR-Cas9 gene edition was used to selectively abrogate GPR183 gene expression in B-NHL cells. In vivo, drug efficacy was determined in immunodeficient (NSG mice) or immune-competent (chicken embryo chorioallantoic membrane (CAM)) B-NHL xenograft models.

Results

Using a panel of B-NHL co-cultures, we show that TG-1801, by disrupting the CD47-SIRPα axis, potentiates anti-CD20-mediated ADCC and ADCP. This led to a remarkable and durable antitumor effect of the triplet therapy composed by TG-1801 and U2 regimen, in vitro, as well as in mice and CAM xenograft models of B-NHL. Transcriptomic analysis also uncovered the upregulation of the G protein-coupled and inflammatory receptor, GPR183, as a crucial event associated with the efficacy of the triplet combination. Genetic depletion and pharmacological inhibition of GPR183 impaired ADCP initiation, cytoskeleton remodeling and cell migration in 2D and 3D spheroid B-NHL co-cultures, and disrupted macrophage-mediated control of tumor growth in B-NHL CAM xenografts.

Conclusions

Altogether, our results support a crucial role for GPR183 in the recognition and elimination of malignant B cells upon concomitant targeting of CD20, CD47 and PI3Kδ, and warrant further clinical evaluation of this triplet regimen in B-NHL.
Clinical analysis of 173 pediatric patients with antibody-mediated autoimmune diseases of the central nervous system: a single-center cohort study
Authors: Kang Qingyun , Liao Hongmei , Yang Liming , Fang Hongjun , Ning Zeshu , Liao Caishi , Gan Siyi , Wu Liwen
Published: April 2023

Background

Antibody-mediated disorders of the central nervous system (CNS) have seen a gradual rise in their incidence and prevalence. This retrospective observational study aimed to investigate the clinical characteristics and short-term prognosis of children with antibody-mediated CNS autoimmune diseases at Hunan Children’s Hospital.

Methods

We collected the clinical data of 173 pediatric patients diagnosed with antibody-mediated CNS autoimmune diseases between June 2014 and June 2021 and analyzed their demographics, clinical features, imaging and laboratory data, treatment, and prognosis.

Results

A total of 187 patients tested positive for anti-neural antibodies and 173 patients were finally diagnosed with antibody-mediated CNS autoimmune diseases after excluding the 14 false-positive cases through clinical phenotypic evaluation and follow-up of treatment outcomes. Of the 173 confirmed patients, 97 (56.06%) were positive for anti-NMDA-receptor antibody, 48 (27.75%) for anti-MOG antibody, 30 (17.34%) for anti-GFAP antibody, 5 (2.89%) for anti-CASPR2 antibody, 3 (1.73%) for anti-AQP4 antibody, 2 (1.16%) for anti-GABABR antibody, and 1 (0.58%) for anti-LGI1antibody. Anti-NMDAR encephalitis was the most commonly seen among the patients, followed by MOG antibody-associated disorders and autoimmune GFAP astrocytopathy. Psycho-behavioral abnormalities, seizures, involuntary movements, and speech disorder were the most common clinical presentations of anti-NMDAR encephalitis, while fever, headache, and disturbance of consciousness or vision were the most seen among patients with MOG antibody-associated disorders or autoimmune GFAP astrocytopathy. The coexistence of multiple anti-neural antibodies was detected in 13 patients, among which 6 cases had coexistent anti-NMDAR and anti-MOG antibodies (including 1 case with anti-GFAP antibody also), 3 cases had coexistent anti-NMDAR and anti-GFAP antibodies, 3 cases had coexistent anti-MOG and anti-GFAP antibodies, 1 case had coexistent anti-NMDAR and anti-CASPR2 antibodies, and 1 case had coexistent anti-GABABR and anti-CASPR2 antibodies. All the survivors were followed up for at least 12 months; 137 recovered completely, 33 had varying sequelae, and 3 died; 22 had one or more relapses.

Conclusion

Antibody-mediated CNS autoimmune diseases occur in children of all ages. Most such pediatric patients have a good response to immunotherapy. Despite the low mortality rate, some survivors have a non-negligible risk of developing relapses.
Potential common molecular mechanisms between Sjögren syndrome and inclusion body myositis: a bioinformatic analysis and in vivo validation
Authors: Zeng Li , Chen Kai , Xiao Feng , Zhu Chun-yan , Bai Jia-ying , Tan Song , Long Li , Wang Yi , Zhou Qiao
Published: April 2023

Background

Inclusion body myositis (IBM) is a slowly progressive inflammatory myopathy that typically affects the quadriceps and finger flexors. Sjögren’s syndrome (SS), an autoimmune disorder characterized by lymphocytic infiltration of exocrine glands has been reported to share common genetic and autoimmune pathways with IBM. However, the exact mechanism underlying their commonality remains unclear. In this study, we investigated the common pathological mechanisms involved in both SS and IBM using a bioinformatic approach.

Methods

IBM and SS gene expression profiles were obtained from the Gene Expression Omnibus (GEO). SS and IBM coexpression modules were identified using weighted gene coexpression network analysis (WGCNA), and differentially expressed gene (DEG) analysis was applied to identify their shared DEGs. The hidden biological pathways were revealed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Furthermore, protein−protein interaction (PPI) networks, cluster analyses, and hub shared gene identification were conducted. The expression of hub genes was validated by reverse transcription quantitative polymerase chain reaction (RT−qPCR). We then analyzed immune cell abundance patterns in SS and IBM using single-sample gene set enrichment analysis (ssGSEA) and investigated their association with hub genes. Finally, NetworkAnalyst was used to construct a common transcription factor (TF)-gene network.

Results

Using WGCNA, we found that 172 intersecting genes were closely related to viral infection and antigen processing/presentation. Based on DEG analysis, 29 shared genes were found to be upregulated and enriched in similar biological pathways. By intersecting the top 20 potential hub genes from the WGCNA and DEG sets, three shared hub genes (PSMB9, CD74, and HLA-F) were derived and validated to be active transcripts, which all exhibited diagnostic values for SS and IBM. Furthermore, ssGSEA showed similar infiltration profiles in IBM and SS, and the hub genes were positively correlated with the abundance of immune cells. Ultimately, two TFs (HDGF and WRNIP1) were identified as possible key TFs.

Conclusion

Our study identified that IBM shares common immunologic and transcriptional pathways with SS, such as viral infection and antigen processing/presentation. Furthermore, both IBM and SS have almost identical immune infiltration microenvironments, indicating similar immune responses may contribute to their association.
Full characterization of the three pathways of the complement system in patients with systemic lupus erythematosus
Authors: García-González María , Gómez-Bernal Fuensanta , Quevedo-Abeledo Juan C. , Fernández-Cladera Yolanda , González-Rivero Agustín F. , de Vera-González Antonia , de la Rua-Figueroa Iñigo , López-Mejias Raquel , Díaz-González Federico , González-Gay Miguel Á. , Ferraz-Amaro Iván
Published: April 2023

Background

To date a complete characterization of the components of the complement (C) pathways (CLassical, LEctin and ALternative) in patients with systemic lupus erythematosus (SLE) has not been performed. We aimed to assess the function of these three C cascades through functional assays and the measurement of individual C proteins. We then studied how they relate to clinical characteristics.

Methods

New generation functional assays of the three pathways of the C system were assessed in 284 patients with SLE. Linear regression analysis was performed to study the relationship between the activity, severity, and damage of the disease and C system.

Results

Lower values of the functional tests AL and LE were more frequent than those of the CL pathway. Clinical activity was not related to inferior values of C routes functional assays. The presence of increased DNA binding was negatively linked to all three C pathways and products, except for C1-inh and C3a which were positively related. Disease damage revealed a consistent positive, rather than a negative, relationship with pathways and C elements. Anti-ribosomes and anti-nucleosomes were the autoantibodies that showed a greater relationship with C activation, mainly due to the LE and CL pathways. Regarding antiphospholipid antibodies, the most related with C activation were IgG anti-β2GP, predominantly involving the AL pathway.

Conclusion

Not only the CL route, but also the AL and LE are related to SLE features. C expression patterns are linked to disease profiles. While accrual damage was associated with higher functional tests of C pathways, anti-DNA, anti-ribosomes and anti-nucleosomes antibodies, were the ones that showed a higher relationship with C activation, mainly due to the LE and CL pathways.
Serum amyloid A proteins reduce bone mass during mycobacterial infections
Authors: Gomes Ana Cordeiro , Sousa Daniela Monteiro , Oliveira Tiago Carvalho , Fonseca Óscar , Pinto Ricardo J. , Silvério Diogo , Fernandes Ana Isabel , Moreira Ana C. , Silva Tânia , Teles Maria José , Pereira Luísa , Saraiva Margarida , Lamghari Meriem , Gomes Maria Salomé
Published: April 2023

Introduction

Osteopenia has been associated to several inflammatory conditions, including mycobacterial infections. How mycobacteria cause bone loss remains elusive, but direct bone infection may not be required.

Methods

Genetically engineered mice and morphometric, transcriptomic, and functional analyses were used. Additionally, inflammatory mediators and bone turnover markers were measured in the serum of healthy controls, individuals with latent tuberculosis and patients with active tuberculosis.

Results and discussion

We found that infection with Mycobacterium avium impacts bone turnover by decreasing bone formation and increasing bone resorption, in an IFNγ- and TNFα-dependent manner. IFNγ produced during infection enhanced macrophage TNFα secretion, which in turn increased the production of serum amyloid A (SAA) 3. Saa3 expression was upregulated in the bone of both M. avium- and M. tuberculosis-infected mice and SAA1 and 2 proteins (that share a high homology with murine SAA3 protein) were increased in the serum of patients with active tuberculosis. Furthermore, the increased SAA levels seen in active tuberculosis patients correlated with altered serum bone turnover markers. Additionally, human SAA proteins impaired bone matrix deposition and increased osteoclastogenesis in vitro. Overall, we report a novel crosstalk between the cytokine-SAA network operating in macrophages and bone homeostasis. These findings contribute to a better understanding of the mechanisms of bone loss during infection and open the way to pharmacological intervention. Additionally, our data and disclose SAA proteins as potential biomarkers of bone loss during infection by mycobacteria.
Endothelial ACKR1 is induced by neutrophil contact and down-regulated by secretion in extracellular vesicles
Authors: Guo Xinying , Khosraviani Negar , Raju Sneha , Singh Joshya , Farahani Nikki Zamani , Abramian Madlene , Torres Victor J. , Howe Kathryn L. , Fish Jason E. , Kapus Andras , Lee Warren L.
Published: April 2023

Atypical chemokine receptor-1 (ACKR1), previously known as the Duffy antigen receptor for chemokines, is a widely conserved cell surface protein that is expressed on erythrocytes and the endothelium of post-capillary venules. In addition to being the receptor for the parasite causing malaria, ACKR1 has been postulated to regulate innate immunity by displaying and trafficking chemokines. Intriguingly, a common mutation in its promoter leads to loss of the erythrocyte protein but leaves endothelial expression unaffected. Study of endothelial ACKR1 has been limited by the rapid down-regulation of both transcript and protein when endothelial cells are extracted and cultured from tissue. Thus, to date the study of endothelial ACKR1 has been limited to heterologous over-expression models or the use of transgenic mice. Here we report that exposure to whole blood induces ACKR1 mRNA and protein expression in cultured primary human lung microvascular endothelial cells. We found that contact with neutrophils is required for this effect. We show that NF-κB regulates ACKR1 expression and that upon removal of blood, the protein is rapidly secreted by extracellular vesicles. Finally, we confirm that endogenous ACKR1 does not signal upon stimulation with IL-8 or CXCL1. Our observations define a simple method for inducing endogenous endothelial ACKR1 protein that will facilitate further functional studies.
A recombinant Modified Vaccinia virus Ankara expressing prME of tick-borne encephalitis virus affords mice full protection against TBEV infection
Authors: Kubinski Mareike , Beicht Jana , Zdora Isabel , Biermann Jeannine , Puff Christina , Gerlach Thomas , Tscherne Alina , Baumgärtner Wolfgang , Osterhaus Albert D. M. E. , Sutter Gerd , Prajeeth Chittappen Kandiyil , Rimmelzwaan Guus F.
Published: April 2023

Introduction

Tick-borne encephalitis virus (TBEV) is an important human pathogen that can cause a serious disease involving the central nervous system (tick-borne encephalitis, TBE). Although approved inactivated vaccines are available, the number of TBE cases is rising, and breakthrough infections in fully vaccinated subjects have been reported in recent years.

Methods

In the present study, we generated and characterized a recombinant Modified Vaccinia virus Ankara (MVA) for the delivery of the pre-membrane (prM) and envelope (E) proteins of TBEV (MVA-prME).

Results

MVA-prME was tested in mice in comparison with a licensed vaccine FSME-IMMUN® and proved to be highly immunogenic and afforded full protection against challenge infection with TBEV.

Discussion

Our data indicate that MVA-prME holds promise as an improved next-generation vaccine for the prevention of TBE.
A Green’s function-based approach to the concentration tensor fields in arbitrary elastic microstructures
Authors: Jiménez Segura Nabor , Pichler Bernhard L. A. , Hellmich Christian
Published: April 2023

Computational homogenization based on FEM models is the gold standard when it comes to homogenization over a representative volume element (RVE), of so-called complex material microstructures, i.e., such which cannot be satisfactorily represented by an assemblage of homogeneous subdomains called phases. As a complement to the aforementioned models, which depend on the boundary conditions applied to the representative volume element and which, as a rule, do not give direct access to the macro-micro-relations in terms of concentration tensors, we here introduce a Green’s function-based homogenization method for arbitrary inhomogeneous microstructures: Inspired by the ideas underlying traditional phase-based homogenization schemes, such as the Mori-Tanaka or the self-consistent model, the new method rests on mapping, through the strain average rule, the microscopic strain fields associated with an auxiliary problem to the macroscopic strains subjected to the RVE. Thereby, the auxiliary problem is defined on a homogeneous infinite matrix subjected to homogeneous auxiliary strains and to inhomogeneous (fluctuating) polarization stresses representing the fluctuations of the microstiffness field, i.e., the complex microstructure within the RVE. The corresponding microscopic strains appear as the solution of a Fredholm integral equation, delivering a multilinear operator linking the homogeneous auxiliary strains to the microscopic strains. This operator, together with the aforementioned mapping, eventually allows for completing the model in terms of concentration tensor and homogenized stiffness quantification. This is illustrated by example of a sinusoidally fluctuating microstructure, whereby the corresponding singular convolution integrals are analytically evaluated from the solution of the Poisson’s equation, and this evaluation strategy is then analytically verified through a Cauchy principal value analysis, and numerically validated by a state-of-the-art FFT homogenization procedure. For the given example, the novel analytical method is several thousand times faster than an FTT-based computational homogenization procedure.
Association between sarcoidosis and HLA polymorphisms in a Czech population from Central Europe: focus on a relationship with clinical outcome and treatment
Authors: Sikorova K. , Osoegawa K. , Kocourkova L. , Strnad A. , Petrkova J. , Fernández-Viña M. A. , Doubkova M. , Petrek M.
Published: April 2023

Background

Sarcoidosis is an immune-mediated systemic disease with unknown etiology affecting the lung predominantly. The clinical manifestation of sarcoidosis is rather diverse ranging from Löfgren’s syndrome to fibrotic disease. Also, it differs among patients with distinct geographical and ethnic origins, consistent with environmental and genetic factors’ role in its pathogenesis. Of those, the polymorphic genes of the HLA system have been previously implicated in sarcoidosis. Therefore, we have performed an association study in a well-defined cohort of Czech patients aiming to define how variation in HLA genes, may contribute to disease origin and development.

Materials and methods

Total of the 301 Czech unrelated sarcoidosis patients were diagnosed according to international guidelines. In those, HLA typing was performed using next-generation sequencing. The allele frequencies at six HLA loci (HLA-A,-B,-C,-DRB1,-DQA1, and -DQB1) observed in the patients were compared with HLA allele distribution determined in 309 unrelated healthy Czech subjects; sub-analyses of relationships between HLA and distinct sarcoidosis clinical phenotypes were performed. Associations were assessed by two-tailed Fischer’s exact test with correction for multiple comparisons.

Results

We report two variants, HLA-DQB1*06:02, and HLA-DQB1*06:04, as risk factors for sarcoidosis, and three variants, HLA-DRB1*01:01, HLA-DQA1*03:01, and HLA-DQB1*03:02 as protective factors. HLA-B*08:01, HLA-C*07:01, HLA-DRB1*03:01, HLA-DQA1*05:01, and HLA-DQB1*02:01 variants associated with Löfgren’s syndrome, a more benign phenotype. HLA- DRB1*03:01 and HLA-DQA1*05:01 alleles were connected with better prognosis—chest X-ray (CXR) stage 1, disease remission, and non-requirement of corticosteroid treatment. The alleles HLA-DRB1*11:01 and HLA-DQA1*05:05 are associated with more advanced disease represented by the CXR stages 2−4. HLA-DQB1*05:03 associated with sarcoidosis extrapulmonary manifestation.

Conclusion

In our Czech cohort, we document some associations between sarcoidosis and HLA previously described in other populations. Further, we suggest novel susceptibility factors for sarcoidosis, such as HLA-DQB1*06:04, and characterize associations between HLA and sarcoidosis clinical phenotypes in Czech patients. Our study also extends the role of the 8.1 ancestral haplotype (HLA-A*01:01∼HLA-B*08:01∼HLA-C*07:01∼HLA-DRB1*03:01∼HLA-DQA1*05:01∼HLA-DQB1*02:01), already implicated in autoimmune diseases, as a possible predictor of better prognosis in sarcoidosis. The general translational application of our newly reported findings for personalized patient care should be validated by an independent study from another, international referral center.
Molecular epidemiology and comparative genomics of carbapenemase-producing Escherichia coli isolates from 19 tertiary hospitals in China from 2019 to 2020
Authors: Ko Weihsin , Tseng Songlu , Chou Chiahsin , Li Tianmeng , Li Rose , Zhang Yaqiao , Li Yun , Lv Yuan
Published: April 2023

Background

The clinical use of carbapenems is facing challenges due to increased carbapenemase-producing Escherichia coli (CP-EC) infections over the past decade. Meanwhile, whole-genome sequencing (WGS) is an important method for bacterial epidemiological research. We aim to provide more gene-based surveys to explore the genomics and occurrence of CP-EC in China.

Methods

A total of 780 Escherichia coli isolates were collected by the China Antimicrobial Resistance Surveillance Trial (CARST) from 2019 to 2020. An antibacterial susceptibility test was performed by using the agar dilution method. CP-EC were detected by the modified carbapenem inactivation method (mCIM), EDTA-modified carbapenem inactivation method (eCIM), and polymerase chain reaction (PCR). Homology analysis was performed by multilocus sequence typing (MLST). A conjugation experiment was performed to verify the transferability of plasmids carrying carbapenemase genes. WGS was conducted to explore the gene-environment of the carbapenemase gene.

Result

Of the 780 Escherichia coli isolates, 31 isolates were insensitive to carbapenem with a rate of 4%. Among them, 13 CP-EC isolates had transferability of the blaNDM gene. These isolates belonged to nine distinct sequence types (STs), with some correlation. We found that two (2/13, 15.4%) of the CP-EC isolates that were collected from blood specimens were highly pathogenic and also showed high transferability of the blaNDM gene. In addition, eight (8/13, 61.5%) of the CP-EC isolates were found to be multidrug-resistant.

Conclusion

With the increasing use of carbapenem, CP-EC isolates accounted for nearly half of the total carbapenem-insensitive Escherichia coli isolates. Our findings highlight the urgent need to pay attention to CP-EC isolates in bloodstream infections and ESBL-producing CP-EC isolates. Based on the One Health concept, we suggest various measures, including the development of bacterial vaccines, antibiotic management, and establishment of better medical environments, to avoid the outbreak of CP-EC.
Chitosan can improve antimicrobial treatment independently of bacterial lifestyle, biofilm biomass intensity and antibiotic resistance pattern in non-aureus staphylococci (NAS) isolated from bovine clinical mastitis
Authors: Breser Maria Laura , Tisera Lucia , Orellano Maria Soledad , Bohl Luciana Paola , Isaac Paula , Bianco Ismael , Porporatto Carina
Published: April 2023

Bovine mastitis is the most frequent and costly disease that affects dairy cattle. Non-aureus staphylococci (NAS) are currently one of the main pathogens associated with difficult-to-treat intramammary infections. Biofilm is an important virulence factor that can protect bacteria against antimicrobial treatment and prevent their recognition by the host’s immune system. Previously, we found that chronic mastitis isolates which were refractory to antibiotic therapy developed strong biofilm biomass. Now, we evaluated the influence of biofilm biomass intensity on the antibiotic resistance pattern in strong and weak biofilm-forming NAS isolates from clinical mastitis. We also assessed the effect of cloxacillin (Clx) and chitosan (Ch), either alone or in combination, on NAS isolates with different lifestyles and abilities to form biofilm. The antibiotic resistance pattern was not the same in strong and weak biofilm producers, and there was a significant association (p ≤ 0.01) between biofilm biomass intensity and antibiotic resistance. Bacterial viability assays showed that a similar antibiotic concentration was effective at killing both groups when they grew planktonically. In contrast, within biofilm the concentrations needed to eliminate strong producers were 16 to 128 times those needed for weak producers, and more than 1,000 times those required for planktonic cultures. Moreover, Ch alone or combined with Clx had significant antimicrobial activity, and represented an improvement over the activity of the antibiotic on its own, independently of the bacterial lifestyle, the biofilm biomass intensity or the antibiotic resistance pattern. In conclusion, the degree of protection conferred by biofilm against antibiotics appears to be associated with the intensity of its biomass, but treatment with Ch might be able to help counteract it. These findings suggest that bacterial biomass should be considered when designing new antimicrobial therapies aimed at reducing antibiotic concentrations while improving cure rates.
Changes in soil microbial biomass and organic C pools improve the sustainability of perennial grass and legume system under organic nutrient management
Authors: Rai Arvind Kumar , Basak Nirmalendu , Dixit Anoop Kumar , Rai Suchit Kumar , Das Sanjoy Kumar , Singh J. B. , Kumar Sunil , Kumar T. Kiran , Chandra Priyanka , Sundha Parul , Bedwal Sandeep
Published: April 2023

Introduction

The perennial grass–legume cropping system benefits soil because of its high biomass turnover, cover cropping nature, and different foraging behaviors. We investigated the response of soil organic carbon (SOC) pools and their stock to organic and inorganic nutrient management in the Guinea grass and legume (cowpea-Egyptian clover) cropping system.

Methods

Depth-wise soil samples were collected after harvesting the Egyptian clover. Based on the ease of oxidation with chromic acid, different pools of SOC oxidizable using the Walkley–Black C method, very labile, labile, less labile, non-labile; and dissolved organic C (DOC), microbial biomass C (MBC), and total organic C (TOC) in soils were analyzed for computing several indices of SOC.

Result and discussion

After 10 years of crop cycles, FYM and NPKF nutrient management recorded greater DOC, MBC, SOC stocks, and C sequestration than the NPK. Stocks of all SOC pools and carbon management index (CMI) decreased with soil depth. A significant improvement in CMI, stratification ratio, sensitivity indices, and sustainable yield index was observed under FYM and NPKF. This grass–legume intercropping system maintained a positive carbon balance sequestered at about 0.8Mg C ha−1 after 10 years without any external input. Approximately 44–51% of the applied carbon through manure was stabilized with SOC under this cropping system. The DOC, MBC, and SOC in passive pools were identified for predicting dry fodder yield. This study concludes that the application of organics in the perennial grass–legume inter cropping system can maintain long-term sustainability, enhance the C sequestration, and offset the carbon footprint of the farm enterprises.