bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensively prognostic and immunological analysis of snail family transcriptional repressor 2 in pan-cancer and identification in pancreatic carcinoma
Authors: Zhang Dandan , Jiang Zhenhong , Hu Jianping , Sun Xiaoyun , Zheng Yan , Shen Yang
Published: May 2023

Background

Snail family transcriptional repressor 2 (SNAI2) is a transcription factor that induces epithelial to mesenchymal transition in neoplastic epithelial cells. It is closely related to the progression of various malignancies. However, the significance of SNAI2 in human pan-cancer is still largely unknown.

Methods

The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE) databases were taken to examine the SNAI2 expression pattern in tissues and cancer cells. The link between SNAI2 gene expression levels and prognosis, as well as immune cell infiltration, was investigated using the Kaplan-Meier technique and Spearman correlation analysis. We also explored the expression and distribution of SNAI2 in various tumor tissues and cells by the THPA (Human Protein Atlas) database. We further investigated the relationship between SNAI2 expression levels and immunotherapy response in various clinical immunotherapy cohorts. Finally, the immunoblot was used to quantify the SNAI2 expression levels, and the proliferative and invasive ability of pancreatic cancer cells was determined by colony formation and transwell assays.

Results

We discovered heterogeneity in SNAI2 expression in different tumor tissues and cancer cell lines by exploring public datasets. The genomic alteration of SNAI2 existed in most cancers. Also, SNAI2 exhibits prognosis predictive ability in various cancers. SNAI2 was significantly correlated with immune-activated hallmarks, cancer immune cell infiltrations, and immunoregulators. It’s worth noting that SNAI2 expression is significantly related to the effectiveness of clinical immunotherapy. SNAI2 expression was also found to have a high correlation with the DNA mismatch repair (MMR) genes and DNA methylation in many cancers. Finally, the knockdown of SNAI2 significantly weakened the proliferative and invasive ability of pancreatic cancer cells.

Conclusion

These findings suggested that SNAI2 could be used as a biomarker in human pan-cancer to detect immune infiltration and poor prognosis, which provides a new idea for cancer treatment.
Single cell RNA sequencing reveals distinct clusters of Irf8-expressing pulmonary conventional dendritic cells
Authors: Jirmo Adan Chari , Grychtol Ruth , Gaedcke Svenja , Liu Bin , DeStefano Stephanie , Happle Christine , Halle Olga , Monteiro Joao T. , Habener Anika , Breiholz Oliver D. , DeLuca David , Hansen Gesine
Published: May 2023

A single population of interferon-regulatory factor 8 (Irf8)-dependent conventional dendritic cell (cDC type1) is considered to be responsible for both immunogenic and tolerogenic responses depending on the surrounding cytokine milieu. Here, we challenge this concept of an omnipotent single Irf8-dependent cDC1 cluster through analysis of pulmonary cDCs at single cell resolution. We report existence of a pulmonary cDC1 cluster lacking Xcr1 with an immunogenic signature that clearly differs from the Xcr1 positive cDC1 cluster. The Irf8+Batf3+Xcr1- cluster expresses high levels of pro-inflammatory genes associated with antigen presentation, migration and co-stimulation such as Ccr7, Cd74, MHC-II, Ccl5, Il12b and Relb while, the Xcr1+ cDC1 cluster expresses genes corresponding to immune tolerance mechanisms like Clec9a, Pbx1, Cadm1, Btla and Clec12a. In concordance with their pro-inflammatory gene expression profile, the ratio of Xcr1- cDC1s but not Xcr1+cDC1 is increased in the lungs of allergen-treated mice compared to the control group, in which both cDC1 clusters are present in comparable ratios. The existence of two distinct Xcr1+ and Xcr1- cDC1 clusters is furthermore supported by velocity analysis showing markedly different temporal patterns of Xcr1- and Xcr1+cDC1s. In summary, we present evidence for the existence of two different cDC1 clusters with distinct immunogenic profiles in vivo. Our findings have important implications for DC-targeting immunomodulatory therapies.
Influence of bariatric surgery on the peripheral blood immune system of female patients with morbid obesity revealed by high-dimensional mass cytometry
Authors: Gihring Adrian , Gärtner Fabian , Mayer Laura , Roth Aileen , Abdelrasoul Hend , Kornmann Marko , Elad Leonard , Knippschild Uwe
Published: May 2023

Introduction

Obesity is associated with low-grade chronic inflammation, altered levels of adipocytokines, and impaired regulation of gastrointestinal hormones. Secreted, these factors exert immunostimulatory functions directly influencing peripheral immune cells.

Methods

In the realm of this study, we aimed to investigate the composition and activation status of peripheral blood immune cells in female patients with morbid obesity compared to lean controls using high-dimensional mass cytometry. Besides, we also assessed the influence of bariatric surgery with respect to its ability to reverse obesity-associated alterations within the first-year post-surgery.

Results

Patients with morbid obesity showed typical signs of chronic inflammation characterized by increased levels of CRP and fibrinogen. Apart from that, metabolic alterations were characterized by increased levels of leptin and resistin as well as decreased levels of adiponectin and ghrelin compared to the healthy control population. All these however, except for ghrelin levels, rapidly normalized after surgery with regard to control levels. Furthermore, we found an increased population of monocytic CD14+, HLA-DR-, CD11b+, CXCR3+ cells in patients with morbid obesity and an overall reduction of the HLA-DR monocytic expression compared to the control population. Although CD14+, HLA-DR-, CD11b+, CXCR3+ decreased after surgery, HLA-DR expression did not recover within 9 – 11 months post-surgery. Moreover, compared to the control population, patients with morbid obesity showed a perturbed CD4+ T cell compartment, characterized by a strongly elevated CD127+ memory T cell subset and decreased naïve T cells, which was not recovered within 9 – 11 months post-surgery. Although NK cells showed an activated phenotype, they were numerically lower in patients with morbid obesity when compared to healthy controls. The NK cell population further decreased after surgery and did not recover quantitatively within the study period.

Conclusions

Our results clearly demonstrate that the rapid adaptions in inflammatory parameters and adipocytokine levels that occur within the first year post-surgery do not translate to the peripheral immune cells. Apart from that, we described highly affected, distinct immune cell subsets, defined as CD127+ memory T cells and monocytic CD14+, HLA-DR, CD11b+, CXCR3+ cells, that might play a significant role in understanding and further decoding the etiopathogenesis of morbid obesity.
Heterologous vaccination with inactivated vaccine and mRNA vaccine augments antibodies against both spike and nucleocapsid proteins of SARS-CoV-2: a local study in Macao
Authors: Ng Hoi Man , Lei Chon Lok , Fu Siyi , Li Enqin , Leong Sek In , Nip Chu Iong , Choi Nga Man , Lai Kai Seng , Tang Xi Jun , Lei Chon Leng , Xu Ren-He
Published: May 2023

The mRNA vaccines (RVs) can reduce the severity and mortality of severe acute respiratory syndrome coronavirus (SARS-CoV-2). However, almost only the inactivated vaccines (IVs) but no RVs had been used in mainland China until most recently, and the relaxing of its anti-pandemic strategies in December 2022 increased concerns about new outbreaks. In comparison, many of the citizens in Macao Special Administrative Region of China received three doses of IV (3IV) or RV (3RV), or 2 doses of IV plus one booster of RV (2IV+1RV). By the end of 2022, we recruited 147 participants with various vaccinations in Macao and detected antibodies (Abs) against the spike (S) protein and nucleocapsid (N) protein of the virus as well as neutralizing antibodies (NAb) in their serum. We observed that the level of anti-S Ab or NAb was similarly high with both 3RV and 2IV+1RV but lower with 3IV. In contrast, the level of anti-N Ab was the highest with 3IV like that in convalescents, intermediate with 2IV+1RV, and the lowest with 3RV. Whereas no significant differences in the basal levels of cytokines related to T-cell activation were observed among the various vaccination groups before and after the boosters. No vaccinees reported severe adverse events. Since Macao took one of the most stringent non-pharmaceutical interventions in the world, this study possesses much higher confidence in the vaccination results than many other studies from highly infected regions. Our findings suggest that the heterologous vaccination 2IV+1RV outperforms the homologous vaccinations 3IV and 3RV as it induces not only anti-S Ab (to the level as with 3RV) but also anti-N antibodies (via the IV). It combines the advantages of both RV (to block the viral entry) and IV (to also intervene the subsequent pathological processes such as intracellular viral replication and interference with the signal transduction and hence the biological functions of host cells).
Biomarkers detected in cord blood predict vaccine responses in young infants
Authors: Baloh Carolyn H. , Venturi Guglielmo M. , Fischer Bernard M. , Sadder Liane S. , Kim-Chang Julie J. , Chan Cliburn , De Paris Kristina , Yin Li , Aldrovandi Grace M. , Goodenow Maureen M. , Sleasman John W.
Published: May 2023

Introduction

Factors influencing vaccine immune priming in the first year of life involve both innate and adaptive immunity but there are gaps in understanding how these factors sustain vaccine antibody levels in healthy infants. The hypothesis was that bioprofiles associated with B cell survival best predict sustained vaccine IgG levels at one year.

Methods

Longitudinal study of plasma bioprofiles in 82 term, healthy infants, who received standard recommended immunizations in the United States, with changes in 15 plasma biomarker concentrations and B cell subsets associated with germinal center development monitored at birth, soon after completion of the initial vaccine series at 6 months, and prior to the 12-month vaccinations. Post vaccination antibody IgG levels to Bordetella pertussis, tetanus toxoid, and conjugated Haemophilus influenzae type B (HiB) were outcome measures.

Results

Using a least absolute shrinkage and selection operator (lasso) regression model, cord blood (CB) plasma IL-2, IL-17A, IL-31, and soluble CD14 (sCD14) were positively associated with pertussis IgG levels at 12 months, while CB plasma concentrations of APRIL and IL-33 were negatively associated. In contrast, CB concentrations of sCD14 and APRIL were positively associated with sustained tetanus IgG levels. A separate cross-sectional analysis of 18 mother/newborn pairs indicated that CB biomarkers were not due to transplacental transfer, but rather due to immune activation at the fetal/maternal interface. Elevated percentages of cord blood switched memory B cells were positively associated with 12-month HiB IgG levels. BAFF concentrations at 6 and 12 months were positively associated with pertussis and HiB IgG levels respectively.

Discussion

Sustained B cell immunity is highly influenced by early life immune dynamics beginning prior to birth. The findings provide important insights into how germinal center development shapes vaccine responses in healthy infants and provide a foundation for studies of conditions that impair infant immune development.
CD16+ monocytes are involved in the hyper-inflammatory state of Prader-Willi Syndrome by single-cell transcriptomic analysis
Authors: Xu Yunyun , Hou Xu , Guo Honglin , Yao Zhenyu , Fan Xiude , Xu Chao , Li Guimei , Wang Yanzhou , Sun Yan , Gao Ling , Song Yongfeng , Zhao Jiajun
Published: May 2023

Background

Patients with Prader-Willi syndrome (PWS) have a reduced life expectancy due to inflammation-related disease including cardiovascular disease and diabetes. Abnormal activation of peripheral immune system is postulated as a contributor. However, detailed features of the peripheral immune cells in PWS have not been fully elucidated.

Methods

Serum inflammatory cytokines were measured in healthy controls (n=13) and PWS patients (n=10) using a 65- multiplex cytokine assays. Changes of the peripheral immune cells in PWS was assessed by single-cell RNA sequencing (scRNA-seq) and high-dimensional mass cytometry (CyTOF) using peripheral blood mononuclear cells (PBMCs) from PWS patients (n=6) and healthy controls (n=12).

Results

PWS patients exhibited hyper-inflammatory signatures in PBMCs and monocytes were the most pronounced. Most inflammatory serum cytokines were increased in PWS, including IL-1β, IL-2R, IL-12p70, and TNF-α. The characteristics of monocytes evaluated by scRNA-seq and CyTOF showed that CD16+ monocytes were significantly increased in PWS patients. Functional pathway analysis revealed that CD16+ monocytes upregulated pathways in PWS were closely associated with TNF/IL-1β- driven inflammation signaling. The CellChat analysis identified CD16+ monocytes transmitted chemokine and cytokine signaling to drive inflammatory process in other cell types. Finally, we explored the PWS deletion region 15q11–q13 might be responsible for elevated levels of inflammation in the peripheral immune system.

Conclusion

The study highlights that CD16+ monocytes contributor to the hyper-inflammatory state of PWS which provides potential targets for immunotherapy in the future and expands our knowledge of peripheral immune cells in PWS at the single cell level for the first time.
Vaccine development for mosquito-borne viral diseases
Authors: Huang Zhiwei , Zhang Yuxuan , Li Hongyu , Zhu Jiajie , Song Wanchen , Chen Keda , Zhang Yanjun , Lou Yongliang
Published: May 2023

Mosquito-borne viral diseases are a group of viral illnesses that are predominantly transmitted by mosquitoes, including viruses from the Togaviridae and Flaviviridae families. In recent years, outbreaks caused by Dengue and Zika viruses from the Flaviviridae family, and Chikungunya virus from the Togaviridae family, have raised significant concerns for public health. However, there are currently no safe and effective vaccines available for these viruses, except for CYD-TDV, which has been licensed for Dengue virus. Efforts to control the transmission of COVID-19, such as home quarantine and travel restrictions, have somewhat limited the spread of mosquito-borne viral diseases. Several vaccine platforms, including inactivated vaccines, viral-vector vaccines, live attenuated vaccines, protein vaccines, and nucleic acid vaccines, are being developed to combat these viruses. This review analyzes the various vaccine platforms against Dengue, Zika, and Chikungunya viruses and provides valuable insights for responding to potential outbreaks.
A novel precision-serology assay for SARS-CoV-2 infection based on linear B-cell epitopes of Spike protein
Authors: Lundin Samuel B. , Kann Hanna , Fulurija Alma , Andersson Björn , Nakka Sravya S. , Andersson Lars-Magnus , Gisslén Magnus , Harandi Ali M.
Published: May 2023

Introduction

The COVID-19 pandemic illustrates the need for serology diagnostics with improved accuracy. While conventional serology based on recognition of entire proteins or subunits thereof has made significant contribution to the antibody assessment space, it often suffers from sub-optimal specificity. Epitope-based, high-precision, serology assays hold potential to capture the high specificity and diversity of the immune system, hence circumventing the cross-reactivity with closely related microbial antigens.

Methods

We herein report mapping of linear IgG and IgA antibody epitopes of the SARS-CoV-2 Spike (S) protein in samples from SARS-CoV-2 exposed individuals along with certified SARS-CoV-2 verification plasma samples using peptide arrays.

Results

We identified 21 distinct linear epitopes. Importantly, we showed that pre-pandemic serum samples contain IgG antibodies reacting to the majority of protein S epitopes, most likely as a result of prior infection with seasonal coronaviruses. Only 4 of the identified SARS-CoV-2 protein S linear epitopes were specific for SARS-CoV-2 infection. These epitopes are located at positions 278-298 and 550-586, just proximal and distal to the RBD, as well as at position 1134-1156 in the HR2 subdomain and at 1248-1271 in the C-terminal subdomain of protein S. To substantiate the applicability of our findings, we tested three of the high-accuracy protein S epitopes in a Luminex assay, using a certified validation plasma sample set from SARS-CoV-2 infected individuals. The Luminex results were well aligned with the peptide array results, and correlated very well with in-house and commercial immune assays for RBD, S1 and S1/S2 domains of protein S.

Conclusion

We present a comprehensive mapping of linear B-cell epitopes of SARS-CoV-2 protein S, that identifies peptides suitable for a precision serology assay devoid of cross-reactivity. These results have implications for development of highly specific serology test for exposure to SARS-CoV-2 and other members of the coronaviridae family, as well as for rapid development of serology tests for future emerging pandemic threats.
Evaluation of neoadjuvant immunotherapy and traditional neoadjuvant therapy for resectable esophageal cancer: a systematic review and single-arm and network meta-analysis
Authors: Wang Hesong , Song Chunyang , Zhao Xiaohan , Deng Wenzhao , Dong Jing , Shen Wenbin
Published: May 2023

Objective

This systematic review and meta-analysis aimed to investigate the role of neoadjuvant immunochemotherapy with or without radiotherapy [NIC(R)T] compared to traditional neoadjuvant therapies, without immunotherapy [NC(R)T].

Summary background data

NCRT followed by surgical resection is recommended for patients with early-stage esophageal cancer. However, it is uncertain whether adding immunotherapy to preoperative neoadjuvant therapy would improve patient outcomes when radical surgery is performed following neoadjuvant therapy.

Methods

We searched PubMed, Web of Science, Embase, and Cochrane Central databases, as well as international conference abstracts. Outcomes included R0, pathological complete response (pCR), major pathological response (mPR), overall survival (OS) and disease-free survival (DFS) rates.

Results

We included data from 5,034 patients from 86 studies published between 2019 and 2022. We found no significant differences between NICRT and NCRT in pCR or mPR rates. Both were better than NICT, with NCT showing the lowest response rate. Neoadjuvant immunotherapy has a significant advantage over traditional neoadjuvant therapy in terms of 1-year OS and DFS, with NICT having better outcomes than any of the other three treatments. There were no significant differences among the four neoadjuvant treatments in terms of R0 rates.

Conclusions

Among the four neoadjuvant treatment modalities, NICRT and NCRT had the highest pCR and mPR rates. There were no significant differences in the R0 rates among the four treatments. Adding immunotherapy to neoadjuvant therapy improved 1-year OS and DFS, with NICT having the highest rates compared to the other three modalities.

Systematic Review Registration

https://inplasy.com/inplasy-2022-12-0060/, identifier INPLASY2022120060.
Krüppel-like factor 2: a central regulator of B cell differentiation and plasma cell homing
Authors: Wittner Jens , Schuh Wolfgang
Published: May 2023

The development of B cells, their activation and terminal differentiation into antibody-producing plasma cells are characterized by alternating phases of proliferation and quiescence that are controlled by complex transcriptional networks. The spatial and anatomical organization of B cells and plasma cells inside lymphoid organs as well as their migration within lymphoid structures and between organs are prerequisites for the generation and the maintenance of humoral immune responses. Transcription factors of the Krüppel-like family are critical regulators of immune cell differentiation, activation, and migration. Here, we discuss the functional relevance of Krüppel-like factor 2 (KLF2) for B cell development, B cell activation, plasma cell formation and maintenance. We elaborate on KLF2-mediated regulation of B cell and plasmablast migration in the context of immune responses. Moreover, we describe the importance of KLF2 for the onset and the progression of B cell-related diseases and malignancies.
Stromal depletion by TALEN-edited universal hypoimmunogenic FAP-CAR T cells enables infiltration and anti-tumor cytotoxicity of tumor antigen-targeted CAR-T immunotherapy
Authors: Das Shipra , Valton Julien , Duchateau Philippe , Poirot Laurent
Published: May 2023

Adoptive cell therapy based on chimeric antigen receptor (CAR)-engineered T-cells has proven to be lifesaving for many cancer patients. However, its therapeutic efficacy has so far been restricted to only a few malignancies, with solid tumors proving to be especially recalcitrant to efficient therapy. Poor intra-tumor infiltration by T cells and T cell dysfunction due to a desmoplastic, immunosuppressive microenvironment are key barriers for CAR T-cell success against solid tumors. Cancer-associated fibroblasts (CAFs) are critical components of the tumor stroma, evolving specifically within the tumor microenvironment (TME) in response to tumor cell cues. The CAF secretome is a significant contributor to the extracellular matrix and a plethora of cytokines and growth factors that induce immune suppression. Together they form a physical and chemical barrier which induces a T cell-excluding ‘cold’ TME. CAF depletion in stroma rich solid tumors can thus provide an opportunity to convert immune evasive tumors susceptible to tumor-antigen CAR T-cell cytotoxicity. Using our TALEN-based gene editing platform we engineered non-alloreactive, immune evasive CAR T-cells (termed UCAR T-cells) targeting the unique CAF marker Fibroblast Activation Protein, alpha (FAP). In an orthotopic mouse model of triple-negative breast cancer (TNBC) composed of patient derived-CAFs and tumor cells, we demonstrate the efficacy of our engineered FAP UCAR T-cells in CAF depletion, reduction of desmoplasia and successful tumor infiltration. Furthermore, while previously resistant, pre-treatment with FAP UCAR T-cells now sensitized these tumors to Mesothelin (Meso) UCAR T-cell infiltration and anti-tumor cytotoxicity. Combination therapy of FAP UCAR, Meso UCAR T cells and the checkpoint inhibitor anti-PD-1 significantly reduced tumor burden and prolonged mice survival. Our study thus proposes a novel treatment paradigm for successful CAR T-cell immunotherapy against stroma-rich solid tumors.
Identification of the shared gene signatures and molecular mechanisms between multiple sclerosis and non-small cell lung cancer
Authors: Yang Jingyun , Hu Xiaofei , Wang Yu , Liu Wenying , Zhang Mengjie , Zhang Anmei , Ni Bing
Published: May 2023

Introduction

The association between multiple sclerosis (MS) and non-small cell lung cancer (NSCLC) has been the subject of investigation in clinical cohorts, yet the molecular mechanisms underpinning this relationship remain incompletely understood. To address this, our study aimed to identify shared genetic signatures, shared local immune microenvironment, and molecular mechanisms between MS and NSCLC.

Methods

We selected multiple Gene Expression Omnibus (GEO) datasets, including GSE19188, GSE214334, GSE199460, and GSE148071, to obtain gene expression levels and clinical information from patients or mice with MS and NSCLC. We employed Weighted Gene Co-expression Network Analysis (WGCNA) to investigate co-expression networks linked to MS and NSCLC and used single-cell RNA sequencing (scRNA-seq) analysis to explore the local immune microenvironment of MS and NSCLC and identify possible shared components.

Results

Our analysis identified the most significant shared gene in MS and NSCLC, phosphodiesterase 4A (PDE4A), and we analyzed its expression in NSCLC patients and its impact on patient prognosis, as well as its molecular mechanism. Our results demonstrated that high expression of PDE4A was associated with poor prognoses in NSCLC patients, and Gene Set Enrichment Analysis (GSEA) revealed that PDE4A is involved in immune-related pathways and has a significant regulatory effect on human immune responses. We further observed that PDE4A was closely linked to the sensitivity of several chemotherapy drugs.

Conclusion

Given the limitation of studies investigating the molecular mechanisms underlying the correlation between MS and NSCLC, our findings suggest that there are shared pathogenic processes and molecular mechanisms between these two diseases and that PDE4A represents a potential therapeutic target and immune-related biomarker for patients with both MS and NSCLC.
LncRNA–miRNA–mRNA ceRNA network of different body colors in Plectropomus leopardus
Authors: Hao Ruijuan , Zhu Xiaowen , Tian Changxu , Jiang Mouyan , Huang Yang , Li Guangli , Zhu Chunhua
Published: May 2023

Long non-coding RNAs (lncRNAs) play a multifaceted role in transcriptional regulation, and the potential molecular regulatory mechanisms of lncRNAs and lncRNA–miRNA–mRNA networks in body color formation are of great significance for its selective breeding. Therefore, lncRNAs and lncRNA-miRNA-mRNA ceRNA network of red- and black-colored Plectropomus leopardus were identified and analyzed. Sequencing analyses identified 167 differentially expressed lncRNAs (DELs) between red- and black-colored P. leopardus, including 89 upregulated and 78 downregulated DELs in the red-colored group (false discovery rate (FDR) < 0.05 and |log2FC| > 1). Differentially expressed miRNA (DEM), genes (DEG), and DEL analyses found 605 and 125 negatively co-expressed miRNA–mRNA pairs and lncRNA–miRNA pairs, respectively. Further correlation analysis with Spearman’s correlation coefficient >0.9 as the threshold identified 3,721 lncRNA–mRNA pairs. Then, a competitive endogenous RNA (ceRNA) network of 325 pairs (p < 0.05) was obtained. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of network DEGs showed that melanin metabolic process, lipid metabolism, and immune-related pathway were enriched. The ceRNA network provided interactions among lncRNAs, miRNAs, and mRNAs and extended the molecular foundation of body color formation.
Relative importance of ENSO and IOD on interannual variability of Indonesian Throughflow transport
Authors: Li Aojie , Zhang Yongchui , Hong Mei , Shi Jian , Wang Jing
Published: May 2023

Introduction

The Indonesian Throughflow (ITF) connects the Pacific Ocean and the Indian Ocean. It plays an important role in the global ocean circulation system. The interannual variability of ITF transport is largely modulated by climate modes, such as Central-Pacific (CP) and Eastern-Pacific (EP) El Niño and Indian Ocean Dipole (IOD). However, the relative importance of these climate modes importing on the ITF is not well clarified.

Methods

Dominant roles of the climate modes on ITF in specific periods are quantified by combining a machine learning algorithm of the random forest (RF) model with a variety of reanalysis datasets.

Results

The results reveal that during the period from 1993 to 2019, the average ITF transport derived from high-resolution reanalysis datasets is -14.97 Sv with an intensification trend of -0.06 Sv year-1, which mainly occurred in the upper layer. Four periods, which are 1993–2000, 2002–2008, 2009–2012 and 2013–2019, are identified as Niño 3.4, Dipole Mode Index (DMI), no significant dominant index, and DMI dominated, respectively.

Discussion

The corresponding sea surface height differences between the Northwest Tropical Pacific Ocean (NWP) and Southeast Indian Ocean (SEI) in these three periods when exist dominant index are -0.50 cm, 0.99 cm and -3.22 cm, respectively, which are responsible for the dominance of the climate modes. The study provides a new insight to quantify the response of ITF transport to climate drivers.
Research on the fluid dynamics interaction between submarine sand waves and seawater by seismic oceanography
Authors: Han Tonggang , Chen Jiangxin , He Bingshou , Azevedo Leonardo
Published: May 2023

Introduction

The seafloor is an important interface between the lithosphere and the hydrosphere, where processes related to circulation and energy exchange happen along with various marine processes widely developed in the water column near the seafloor. These processes are still not yet completely understood as there are constraints of submarine detection technology and the interdisciplinary nature of these complex environments. Seismic reflection data have been a preferable tool to study and image these processes due to their characteristics in terms of spatial resolution. In seismic reflection data, submarine sand waves show hair-like reflection configurations with low continuity and wearing-hair style, appearing with an angle with the seafloor. Investigation of the relationship between the characteristics of submarine sand waves induced hair-like reflection configuration and hydrodynamics is crucial for understanding hair-like reflection configuration generation and spatiotemporal evolution.

Methods

This study combines fluid dynamics numerical simulation and seismic oceanography to discuss the seismic response characteristics and formation mechanisms of the hair-like reflection configuration. First, we create a seawater time-variant fluid-dynamical model followed by the numerical simulation of seismic oceanography data. This procedure results in seismic oceanography numerical simulation sections with hair-like reflection configurations for different constant flow conditions forced on the boundary. Optimal matching method is then applied to interpret field seismic reflection sections given the results obtained with the numerical experiments.

Results and discussion

As consequence, the fluid dynamic explanation for the formation mechanism of the hair-like reflection configuration due to differences in seawater thermohaline is proposed. The study provides additional comprehension and further insights into the dynamic process of submarine sand waves induced hair-like reflection configuration using the seismic oceanography method.
Emergency residents' self-perceived readiness for practice: the association of milestones, entrustable professional activities, and professional identities—a multi-institutional survey
Authors: Chang Yu-Che , Khwepeya Madalitso , Nkambule Nothando S. , Chuang Renee S. , Chaou Chung-Hsien
Published: May 2023

Background

As a successful innovation, competency-based medical education and its assessment tools continue to be a key strategy in training future doctors and tracking their performance trajectories. Linked to professional identity, evidence suggests that clinical competence is related to thinking, acting and feeling like a physician. Thus, incorporating the values and attitudes of healthcare professions as part of their professional identity in the clinical workplace improves professional performance.

Methods

Through a cross-sectional study, we examined the association of milestone, entrustable professional activities (EPA) and professional identity using self-reported tools among emergency medicine residents from 12 teaching hospitals across Taiwan. Milestone, EPA and professional identity were assessed using the Emergency Medicine Milestone Scale, Entrustable Professional Activity Scale and Emergency Physician Professional Identity and Value Scale, respectively.

Results

The results of a Pearson correlation indicated a significant positive correlation between milestone-based core competencies and EPAs (r = 0.40 ~ 0.74, p < 0.01). The professional identity domain of skills acquisition, capabilities and practical wisdom was positively correlated with milestone-based core competencies of patient care, medical knowledge, practice-based learning and improvement, and system-based practice (r = 0.18 ~ 0.21, p ≤ 0.05), and six items of EPA (r = 0.16 ~ 0.22, p < 0.05). Additionally, the professional identity domain of professional recognition and self-esteem was positively correlated with practice-based learning and improvement, and system-based practice milestone competencies (r = 0.16 ~ 0.19, p < 0.05).

Conclusion

This study demonstrates milestone and EPA assessment tools are highly linked and therefore, can be synergistically used by supervisors and clinical educators to evaluate clinical performance during residency training. Emergency physicians’ professional identity is partly influenced by the advancement of skills and a resident’s ability to learn, effectively perform tasks and make appropriate medical decisions at the system level in their clinical practice. Further research is warranted to understand the importance of residents’ competency in relation to their professional identity development trajectory during clinical training.
Effectiveness of the use of an oscillating positive expiratory pressure device in bronchiectasis with frequent exacerbations: a single-arm pilot study
Authors: Kim So Rae , Kim Sun-Hyung , Kim Geun-Hyeong , Cho Jun Yeun , Choi Hayoung , Lee Hyun , Ra Seung Won , Lee Ki Man , Choe Kang Hyeon , Oh Yeon-Mok , Shin Yoon Mi , Yang Bumhee
Published: May 2023

Impaired airway clearance in patients with non-cystic fibrosis bronchiectasis causes frequent bacterial infection, chronic inflammation, and progressive tissue destruction. We aimed to evaluate whether an oscillating positive expiratory pressure (OPEP) device could allow effective sputum expectoration and prevent acute exacerbations in patients with bronchiectasis who had frequent acute exacerbations. This open-label, single-arm, prospective study included 17 patients who experienced three or more acute exacerbations in the past year. We evaluated the prevention of acute exacerbations, subjective symptom improvement, and change in sputum amount during the use of the Aerobika (Trudell Medical International, London, ON) OPEP device twice daily for 6  months. Of all enrolled patients, only two acute exacerbations occurred during the study period, indicating a significant decrease compared with the number of acute exacerbations before the device use (p < 0.001). Additionally, Bronchiectasis Health Questionnaire score changed from 58.7 to 66.6, showing significant improvement over the treatment period (p < 0.001). The largest sputum volume was observed 3  months after OPEP device use (baseline: 10 ml, 3rd month 25 ml, p = 0.325). There were no major adverse events related to the use of OPEP devices. Twice-daily physiotherapy with OPEP device in patients with bronchiectasis who have frequent exacerbations may facilitate symptomatic improvement and prevention of acute exacerbations without serious adverse events.
Pruritogenic molecules in the skin of patients with dermatomyositis
Authors: Vincze Anett , Herczeg-Lisztes Erika , Szabó Katalin , Béldi Tibor Gábor , Nagy-Vincze Melinda , Pór Ágnes , Varga József , Dankó Katalin , Biró Tamás , Tóth Balázs István , Griger Zoltán
Published: May 2023

Introduction

Pruritus is a common excruciating symptom in systemic autoimmune diseases such as dermatomyositis (DM) but the pathogenesis is not fully understood. We intended to investigate the targeted expression analysis of candidate molecules involved in the development of pruritus in lesional vs. non-lesional skin samples of patients affected with active DM. We looked for correlations between the investigated pruriceptive signaling molecules, disease activity, and itching sensation of DM patients.

Methods

Interleukins (IL-33 and IL-6), tumor necrosis factor α (TNF-α), peroxisome proliferator-activated receptor γ (PPAR-γ), and ion channels belonging to the transient receptor potential (TRP) family were analyzed. The expression of TNF-α, PPAR-γ, IL-33, IL-6, and TRP channels in lesional DM skin was evaluated by RT-qPCR and immunohistochemistry and was compared with non-lesional DM skin samples. Pruritus, disease activity, and damage of DM were evaluated by the 5-D itch scale and Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), respectively. Statistical analysis was performed with IBM SPSS 28 software.

Results

A total of 17 active DM patients participated in the study. We could show that the itching score was positively correlated with the CDASI activity score (Kendall's tau-b = 0.571; p = 0.003). TNF-α gene expression was significantly higher in lesional DM skin than in non-lesional DM skin (p = 0.009) and differed in the subgroups of patients with different itch intensities (p = 0.038). The mRNA expression of lesional IL-6 correlated positively with 5-D itch and CDASI activity score (Kendall's tau-b = 0.585; p = 0.008 and 0.45; p = 0.013, respectively). TRPV4 expressions were positively correlated with CDASI damage score (Kendall's tau-b = 0.626; p < 0.001), but the mRNA expressions of the TRP family, PPAR-γ, IL-6, and IL-33 were not different in lesional and non-lesional samples. Immunohistochemistry analysis did not find significant alterations in the expressions of TNF-α, PPAR-γ, IL-6, and IL-33 in lesional and non-lesional regions.

Discussion

Our results argue that cutaneous disease activity, TNF-α, and IL-6 might play a central role in DM-associated itch, while TRPV4 plays a central role in tissue regeneration.
Viroid-like RNA-dependent RNA polymerase-encoding ambiviruses are abundant in complex fungi
Authors: Chong Li Chuin , Lauber Chris
Published: May 2023

Ambiviruses are hybrid infectious elements encoding the hallmark gene of RNA viruses, the RNA-dependent RNA polymerase, and self-cleaving RNA ribozymes found in many viroids. Ambiviruses are thought to be pathogens of fungi, although the majority of reported genomes have been identified in metatranscriptomes. Here, we present a comprehensive screen for ambiviruses in more than 46,500 fungal transcriptomes from the Sequence Read Archive (SRA). Our data-driven virus discovery approach identified more than 2,500 ambiviral sequences across the kingdom Fungi with a striking expansion in members of the phylum Basidiomycota representing the most complex fungal organisms. Our study unveils a large diversity of unknown ambiviruses with as little as 27% protein sequence identity to known members and sheds new light on the evolution of this distinct class of infectious agents with RNA genomes. No evidence for the presence of ambiviruses in human microbiomes was obtained from a comprehensive screen of respective metatranscriptomes available in the SRA.
Captivity restructures the gut microbiota of François' langurs (Trachypithecus francoisi)
Authors: Mo Fengxiang , Li Yuhui , Liu Zheng , Zheng Jingjin , Huang Zhonghao
Published: May 2023

Gut microbiota is crucial to primate survival. Data on the gut microbiota of captive and wild animals can provide a physiological and ecological basis for the conservation of rare and endangered species. To study the effect of captivity on the gut microbiota, we examine the difference in the gut microbiota composition between captive and wild Francois' langurs (Trachypithecus francoisi), using 16S rRNA sequencing technology. The results showed that the composition of the gut microbiota of captive and wild langurs was characterized by Firmicutes (51.93 ± 10.07% vs. 76.15 ± 8.37%) and Bacteroidetes (32.43 ± 10.00% vs. 4.82 ± 1.41%) at the phylum level and was characterized by Oscillospiraceae (15.80 ± 5.19% vs. 30.21 ± 4.87%) at the family level. The alpha diversity of gut microbiota in captive langurs was higher than those in wild, such as the Shannon index (4.45 ± 0.33 vs. 3.98 ± 0.19, P < 0.001) and invSimpson index (35.11 ± 15.63 vs. 19.02 ± 4.87, P < 0.001). Principal coordinates analysis (PCoA) results showed significant differences in the composition of gut microbiota between captive and wild langurs at both the phylum and family levels (weight UniFrac algorithm, phylum level: R2 = 0.748, P = 0.001; family level: R2 = 0.685, P = 0.001). The relative abundance of Firmicutes (51.93 ± 10.07%) in captive langurs was lower than that of wild langurs (76.15 ± 8.37%), and the relative abundance of Bacteroidetes (32.43 ± 10.00%) in captive langurs was higher than that of wild (4.82 ± 1.41%). Our study concludes that dietary composition could be a crucial determinant in shaping the gut microbiota of langurs because more fiber-rich foods used by the wild langurs could increase the abundance of Firmicutes, and more simple carbohydrate-rich foods consumed by the captive langurs increase the abundance of Bacteroidetes. We highlight the importance of captivity on the gut microbiota and the need to consider the gut microbiota in animal provision.
Purification and biochemical characterization of SM14est, a PET-hydrolyzing enzyme from the marine sponge-derived Streptomyces sp. SM14
Authors: Carr Clodagh M. , Keller Malene B. , Paul Bijoya , Schubert Sune W. , Clausen Kristine S. R. , Jensen Kenneth , Clarke David J. , Westh Peter , Dobson Alan D. W.
Published: May 2023

The successful enzymatic degradation of polyester substrates has fueled worldwide investigation into the treatment of plastic waste using bio-based processes. Within this realm, marine-associated microorganisms have emerged as a promising source of polyester-degrading enzymes. In this work, we describe the hydrolysis of the synthetic polymer PET by SM14est, a polyesterase which was previously identified from Streptomyces sp. SM14, an isolate of the marine sponge Haliclona simulans. The PET hydrolase activity of purified SM14est was assessed using a suspension-based assay and subsequent analysis of reaction products by UV-spectrophotometry and RP-HPLC. SM14est displayed a preference for high salt conditions, with activity significantly increasing at sodium chloride concentrations from 100 mM up to 1,000 mM. The initial rate of PET hydrolysis by SM14est was determined to be 0.004 s−1 at 45°C, which was increased by 5-fold to 0.02 s−1 upon addition of 500 mM sodium chloride. Sequence alignment and structural comparison with known PET hydrolases, including the marine halophile PET6, and the highly efficient, thermophilic PHL7, revealed conserved features of interest. Based on this work, SM14est emerges as a useful enzyme that is more similar to key players in the area of PET hydrolysis, like PHL7 and IsPETase, than it is to its marine counterparts. Salt-tolerant polyesterases such as SM14est are potentially valuable in the biological degradation of plastic particles that readily contaminate marine ecosystems and industrial wastewaters.
Nucleotide-dependent activities of FtsA regulate the early establishment of a functional divisome during the Escherichia coli cell cycle
Authors: Morrison Josiah J. , Ferreira Colby N. , Siler Evelyn M. , Nelson Katie , Trebino Catherine E. , Piraino Benjamin , Camberg Jodi L.
Published: May 2023

During cell division in Escherichia coli, the highly conserved tubulin homolog FtsZ polymerizes and assembles into a ring-like structure, called the Z-ring, at the site of septation. For recruitment to the membrane surface, FtsZ polymers directly interact with membrane-associated proteins, predominantly FtsA in E. coli. FtsA shares structural homology with actin and, like actin, hydrolyzes ATP. Yeast actin detects nucleotide occupancy through a sensor region adjacent to the nucleotide binding site and adopts distinct conformations in monomeric and filamentous actin. Bacterial actin homologs also display considerable conformational flexibility across different nucleotide-bound states and polymerize. Here, we show that several amino acid residues proximal to the nucleotide binding site in FtsA are critical for function in vitro and in vivo. Each of these residues are important for ATP hydrolysis, phospholipid (PL) binding, ATP-dependent vesicle remodeling, and recruitment to the divisome in vivo, to varying degrees. Notably, we observed that Ser 84 and Glu 14 are essential for ATP-dependent vesicle remodeling and magnesium-dependent membrane release of FtsA from vesicles in vitro, and these defects likely underlie the loss of function by FtsA(E14R) and FtsA(S84L) in vivo. Finally, we demonstrate that FtsA(A188V), which is associated with temperature-sensitive growth in vivo, is defective for rapid ATP hydrolysis and ATP-dependent remodeling of PL vesicles in vitro. Together, our results show that loss of nucleotide-dependent activities by FtsA, such as ATP hydrolysis, membrane binding and release, and, most importantly, ATP-dependent PL remodeling, lead to failed Z-ring assembly and division defects in cells.
The contrasting responses of abundant and rare microbial community structures and co-occurrence networks to secondary forest succession in the subalpine region
Authors: Zhang Xiaoying , Zhao Wenqiang , Kou Yongping , Fang Kai , Liu Yanjiao , He Heliang , Liu Qing
Published: May 2023

Knowledge of variations in abundant and rare soil microbial communities and interactions during secondary forest succession is lacking. Soil samples were gathered from different secondary successional stages (grassland, shrubland, and secondary forest) to study the responses of abundant and rare bacterial and fungal communities, interactions and driving factors to secondary forest succession by Illumina sequencing of the 16S and ITS rRNA genes. The results showed that the α-diversities (Shannon index) of abundant bacteria and fungi revealed no significant changes during secondary forest succession, but increased significantly for rare bacteria. The abundant and rare bacterial and fungal β-diversities changed significantly during secondary forest succession. Network analysis showed no obvious changes in the topological properties (nodes, links, and average degree) of abundant microbial networks during secondary forest succession. In contrast, these properties of the rare microbial networks in the secondary forest were higher than those in the grassland and shrubland, indicating that rare microbial networks are more responsive to secondary forest succession than abundant microorganisms. Additionally, rare microbial networks revealed more microbial interactions and greater network complexity than abundant microbial networks due to their higher numbers of nodes and links. The keystone species differed between the abundant and rare microbial networks and consisted of 1 and 48 keystone taxa in the abundant and rare microbial networks, respectively. Soil TP was the most important influencing factor of abundant and rare bacterial communities. Successional stages and plant richness had the most important influences on abundant and rare fungal communities, respectively. C:P, SM and N:P were mainly related to abundant and rare microbial network topological properties. Our study indicates that abundant and rare microbial communities, interactions and driving factors respond differently to secondary forest succession.
Fermented foods: a perspective on their role in delivering biotics
Authors: Vinderola Gabriel , Cotter Paul D. , Freitas Miguel , Gueimonde Miguel , Holscher Hannah D. , Ruas-Madiedo Patricia , Salminen Seppo , Swanson Kelly S. , Sanders Mary Ellen , Cifelli Christopher J.
Published: May 2023

Fermented foods are often erroneously equated with probiotics. Although they might act as delivery vehicles for probiotics, or other ‘biotic’ substances, including prebiotics, synbiotics, and postbiotics, stringent criteria must be met for a fermented food to be considered a ‘biotic’. Those criteria include documented health benefit, sufficient product characterization (for probiotics to the strain level) and testing. Similar to other functional ingredients, the health benefits must go beyond that of the product’s nutritional components and food matrix. Therefore, the ‘fermented food’ and ‘probiotic’ terms may not be used interchangeably. This concept would apply to the other biotics as well. In this context, the capacity of fermented foods to deliver one, several, or all biotics defined so far will depend on the microbiological and chemical level of characterization, the reproducibility of the technological process used to produce the fermented foods, the evidence for health benefits conferred by the biotics, as well as the type and amount of testing carried out to show the probiotic, prebiotic, synbiotic, and postbiotic capacity of that fermented food.