bluuebunny/crossref_metadata_2025 huggingface dataset:
Tissue specificity drives protective immunity against Staphylococcus aureus infection
Authors: Beesetty Pavani , Si Youhui , Li Zhaotao , Yang Ching , Zhao Fan , Chong Anita S. , Montgomery Christopher P.
Published: August 2022

Infections caused by Staphylococcus aureus range from mild to severe and frequently recur. Emerging evidence suggests that the site and severity of infection drive the potency of elicited immune responses and susceptibility to recurrent infection. In this study, we used tractable mouse models of S. aureus skin infection (SSTI) and pneumonia to determine the relative magnitude of elicited protective immunity. Surprisingly, despite both SSTI and pneumonia eliciting antibody and local effector T cell responses, only SSTI elicited protective antibody and memory T cell responses and subsequent protection against secondary SSTI and pneumonia. The failure of pneumonia to elicit protective immunity was attributed to an inability of S. aureus pneumonia to elicit toxin-specific antibodies that confer protection during secondary infection and was associated with a failure to expand antigen-specific memory T cells. Taken together, these findings emphasize the importance of understanding protective immunity in the context of the tissue-specificity.
Inflammatory stimuli alter bone marrow composition and compromise bone health in the malnourished host
Authors: Osorio E. Yaneth , Gugala Zbigniew , Patterson Grace T. , Palacios Genesis , Cordova Erika , Uscanga-Palomeque Ashanti , Travi Bruno L. , Melby Peter C.
Published: August 2022

Inflammation has a role in the pathogenesis of childhood malnutrition. We investigated the effect of malnutrition and inflammatory challenge on bone marrow composition and bone health. We studied an established murine model of moderate acute malnutrition at baseline and after acute inflammatory challenge with bacterial lipopolysaccharide (LPS), a surrogate of Gram-negative bacterial sepsis, or Leishmania donovani, the cause of visceral leishmaniasis. Both of these infections cause significant morbidity and mortality in malnourished children. Of the 2 stimuli, LPS caused more pronounced bone marrow changes that were amplified in malnourished mice. LPS challenge led to increased inflammatory cytokine expression (Il1b, Il6, and Tnf), inflammasome activation, and inflammatory monocyte accumulation in the bone marrow of malnourished mice. Depletion of inflammatory monocytes in Csfr1-LysMcre-DT malnourished mice significantly reduced the inflammasome activation and IL1-ß production after LPS challenge. The inflammatory challenge also led to increased expansion of mesenchymal stem cells (MSCs), bone marrow adiposity, and expression of genes (Pparg, Adipoq, and Srbp1) associated with adipogenesis in malnourished mice. This suggests that inflammatory challenge promotes differentiation of BM MSCs toward the adipocyte lineage rather than toward bone-forming osteoblasts in the malnourished host. Concurrent with this reduced osteoblastic potential there was an increase in bone-resorbing osteoclasts, enhanced osteoclast activity, upregulation of inflammatory genes, and IL-1B involved in osteoclast differentiation and activation. The resulting weakened bone formation and increased bone resorption would contribute to the bone fragility associated with malnutrition. Lastly, we evaluated the effect of replacing lipid rich in omega-6 fatty acids (corn oil) with lipid-rich in omega-3 fatty acids (fish oil) in the nutrient-deficient diet. LPS-challenged malnourished mice that received dietary fish oil showed decreased expression of inflammatory cytokines and Rankl and reduced osteoclast differentiation and activation in the bone marrow. This work demonstrates that the negative effect of inflammatory challenge on bone marrow is amplified in the malnourished host. Increasing dietary intake of omega-3 fatty acids may be a means to reduce inflammation and improve bone health in malnourished children.
Exploration of the relationship between hippocampus and immune system in schizophrenia based on immune infiltration analysis
Authors: Du Yanhong , Gao Yao , Wu Guangxian , Li Zexuan , Du Xinzhe , Li Junxia , Li Xinrong , Liu Zhifen , Xu Yong , Liu Sha
Published: August 2022

Immune dysfunction has been implicated in the pathogenesis of schizophrenia (SZ). Despite previous studies showing a broad link between immune dysregulation and the central nervous system of SZ, the exact relationship has not been completely elucidated. With immune infiltration analysis as an entry point, this study aimed to explore the relationship between schizophrenia and the immune system in more detail from brain regions, immune cells, genes, and pathways. Here, we comprehensively analyzed the hippocampus (HPC), prefrontal cortex (PFC), and striatum (STR) between SZ and control groups. Differentially expressed genes (DEGs) and functional enrichment analysis showed that three brain regions were closely related to the immune system. Compared with PFC and STR, there were 20 immune-related genes (IRGs) and 42 immune pathways in HPC. The results of immune infiltration analysis showed that the differential immune cells in HPC were effector memory T (Tem) cells. The correlation of immune-related DEGs (IDEGs) and immune cells further analysis showed that NPY, BLNK, OXTR, and FGF12, were moderately correlated with Tem cells. Functional pathway analysis indicated that these four genes might affect Tem by regulating the PI3K-AKT pathway and the neuroactive ligand-receptor interaction pathway. The receiver operating characteristic curve (ROC) analysis results indicated that these four genes had a high diagnostic ability (AUC=95.19%). Finally, the disease animal model was successfully replicated, and further validation was conducted using the real-time PCR and the western blot. These results showed that these gene expression changes were consistent with our previous expression profiling. In conclusion, our findings suggested that HPC in SZ may be more closely related to immune disorders and modulate immune function through Tem, PI3K-Akt pathway, and neuroactive ligand-binding receptor interactions. To the best of our knowledge, the Immucell AI tool has been applied for the first time to analyze immune infiltration in SZ, contributing to a better understanding of the role of immune dysfunction in SZ from a new perspective.
Phosgene-Induced acute lung injury: Approaches for mechanism-based treatment strategies
Authors: Cao Chao , Zhang Lin , Shen Jie
Published: August 2022

Phosgene (COCl2) gas is a chemical intermediate of high-volume production with numerous industrial applications worldwide. Due to its high toxicity, accidental exposure to phosgene leads to various chemical injuries, primarily resulting in chemical-induced lung injury due to inhalation. Initially, the illness is mild and presents as coughing, chest tightness, and wheezing; however, within a few hours, symptoms progress to chronic respiratory depression, refractory pulmonary edema, dyspnea, and hypoxemia, which may contribute to acute respiratory distress syndrome or even death in severe cases. Despite rapid advances in medicine, effective treatments for phosgene-inhaled poisoning are lacking. Elucidating the pathophysiology and pathogenesis of acute inhalation toxicity caused by phosgene is necessary for the development of appropriate therapeutics. In this review, we discuss extant literature on relevant mechanisms and therapeutic strategies to highlight novel ideas for the treatment of phosgene-induced acute lung injury.
Platelet-derived microRNA-223 attenuates TNF-α induced monocytes adhesion to arterial endothelium by targeting ICAM-1 in Kawasaki disease
Authors: Guo Manli , Fan Shunyang , Chen Qian , Jia Cuiping , Qiu Miaoyun , Bu Yun , Tang Wai Ho , Zhang Yuan
Published: August 2022

Background

Kawasaki disease (KD) is an acute vasculitis that may result in permanent coronary artery damage with unknown etiology. Endothelial cell (EC) dysfunction and platelet hyperactivity are the hallmarks of KD. Platelets are involved in the development of endothelial dysfunction. MiR-223 transferred by platelet microparticles (PMPs) has been found to involve in the functional regulation of endothelial cells in sepsis. However, the role of platelet-derived miR-223 in endothelial dysfunction has not yet been investigated in KD.

Objectives

We seek to investigate the role of platelet-derived miR-223 in endothelial dysfunction of KD vasculopathy.

Methods and results

Forty-five acute KD patients and 45 matched controls were randomly recruited in the study. When co-cultured with human coronary artery endothelial cells (HCAECs), KD platelets with higher levels of miR-223 were incorporated into HCAECs, resulting in the horizontal transfer of miR-223. Using KD platelets, PMPs, and platelet-releasate from the same amount of blood co-cultured with HCAECs, we found the increased expression of miR-223 in HCAECs was primarily derived from KD platelets, rather than PMPs or free miRNAs from platelet- releasate. KD platelet-derived miR-223 attenuated TNF-α induced intercellular cell adhesion molecule-1 (ICAM-1) expression in HCAECs. KD platelet-derived miR-223 also suppressed the monocyte adhesion to HCAECs. In vivo, platelet-specific miR-223 knockout (PF4-cre: miR-223flox/flox) C57BL/6 mice and miR-223flox/flox C57BL/6 mice were used. Using Lactobacillus casei cell wall extract (LCWE) to establish KD murine model, we showed that in LCWE-injected PF4-cre: miR-223flox/flox mice, deficiency of platelet-miR-223 exacerbates the medial thickening of the abdominal aorta, increased ICAM-1 expression with concomitant CD45+ inflammatory cells infiltration into the endothelium compared to LCWE-injected miR-223flox/flox mice.

Conclusions

The horizontal transfer of platelet-derived miR-223 suppresses the expression of ICAM-1 in HCAECs, which at least in part attenuates leukocyte adhesion, thereby reducing endothelial damage in KD vasculitis
Dynamically upregulated mast cell CPA3 patterns in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis
Authors: Siddhuraj Premkumar , Jönsson Jimmie , Alyamani Manar , Prabhala Pavan , Magnusson Mattias , Lindstedt Sandra , Erjefält Jonas S.
Published: August 2022

Background

The mast cell-specific metalloprotease CPA3 has been given important roles in lung tissue homeostasis and disease pathogenesis. However, the dynamics and spatial distribution of mast cell CPA3 expression in lung diseases remain unknown.

Methods

Using a histology-based approach for quantitative spatial decoding of mRNA and protein single cell, this study investigates the dynamics of CPA3 expression across mast cells residing in lungs from control subjects and patients with severe chronic obstructive pulmonary disease (COPD) or idiopathic lung fibrosis (IPF).

Results

Mast cells in COPD lungs had an anatomically widespread increase of CPA3 mRNA (bronchioles p < 0.001, pulmonary vessels p < 0.01, and alveolar parenchyma p < 0.01) compared to controls, while granule-stored CPA3 protein was unaltered. IPF lungs had a significant upregulation of both mast cell density, CPA3 mRNA (p < 0.001) and protein (p < 0.05), in the fibrotic alveolar tissue. Spatial expression maps revealed altered mast cell mRNA/protein quotients in lung areas subjected to disease-relevant histopathological alterations. Elevated CPA3 mRNA also correlated to lung tissue eosinophils, CD3 T cells, and declined lung function. Single-cell RNA sequencing of bronchial mast cells confirmed CPA3 as a top expressed gene with potential links to both inflammatory and protective markers.

Conclusion

This study shows that lung tissue mast cell populations in COPD and IPF lungs have spatially complex and markedly upregulated CPA3 expression profiles that correlate with immunopathological alterations and lung function. Given the proposed roles of CPA3 in tissue homeostasis, remodeling, and inflammation, these alterations are likely to have clinical consequences.
Sex hormones and immune system: Menopausal hormone therapy in the context of COVID-19 pandemic
Authors: Averyanova Marina , Vishnyakova Polina , Yureneva Svetlana , Yakushevskaya Oksana , Fatkhudinov Timur , Elchaninov Andrey , Sukhikh Gennady
Published: August 2022

The fatal outcomes of COVID-19 are related to the high reactivity of the innate wing of immunity. Estrogens could exert anti-inflammatory effects during SARS-CoV-2 infection at different stages: from increasing the antiviral resistance of individual cells to counteracting the pro-inflammatory cytokine production. A complex relationship between sex hormones and immune system implies that menopausal hormone therapy (MHT) has pleiotropic effects on immunity in peri- and postmenopausal patients. The definite immunological benefits of perimenopausal MHT confirm the important role of estrogens in regulation of immune functionalities. In this review, we attempt to explore how sex hormones and MHT affect immunological parameters of the organism at different level (in vitro, in vivo) and what mechanisms are involved in their protective response to the new coronavirus infection. The correlation of sex steroid levels with severity and lethality of the disease indicates the potential of using hormone therapy to modulate the immune response and increase the resilience to adverse outcomes. The overall success of MHT is based on decades of experience in clinical trials. According to the current standards, MHT should not be discontinued in COVID-19 with the exception of critical cases.
Autoreactive B cells recruited to lungs by silica exposure contribute to local autoantibody production in autoimmune-prone BXSB and B cell receptor transgenic mice
Authors: Fee Lanette , Kumar Advika , Tighe Robert M. , Foster Mary H.
Published: August 2022

Occupational exposure to inhaled crystalline silica dust (cSiO2) is linked to systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, and anti-neutrophil cytoplasmic autoantibody vasculitis. Each disease has a characteristic autoantibody profile used in diagnosis and implicated in pathogenesis. A role for cSiO2 in modulating humoral autoimmunityin vivois supported by findings in mice, where respirable cSiO2 induces ectopic lymphoid structures as well as inflammation in exposed lungs across genetically diverse backgrounds. In lupus-prone mice cSiO2 exposure also leads to early onset autoantibody production and accelerated disease. Elevated autoantibody levels in bronchoalveolar lavage fluid (BALF) and lung transcriptome analysis suggest that the lung is a hub of cSiO2-evoked autoimmune activity. However, mechanisms by which cSiO2 and lung microenvironments interact to promote autoantibody production remain unclear. We previously demonstrated elevated anti-DNA Ig in BALF but not in lung cell cultures from cSiO2-exposed C57BL/6 mice, suggesting that BALF autoantibodies did not arise locally in this non-autoimmune strain. Autoantibodies were also elevated in BALF of cSiO2-exposed lupus-prone BXSB mice. In this report we test the hypothesis that dysregulated autoreactive B cells recruited to cSiO2-exposed lungs in the context of autoimmune predisposition contribute to local autoantibody production. We found that anti-DNA and anti-myeloperoxidase (MPO) Ig were significantly elevated in cultures of TLR ligand-stimulated lung cells from cSiO2-exposed BXSB mice. To further explore the impact of strain genetic susceptibility versus B cell intrinsic dysfunction on cSiO2-recruited B cell fate, we used an anti-basement membrane autoantibody transgenic (autoAb Tg) mouse line termed M7. In M7 mice, autoAb Tg B cells are aberrantly regulated and escape from tolerance on the C57BL/6 background. Exposure to cSiO2 elicited prominent pulmonary B cell and T cell aggregates and autoAb Tg Ig were readily detected in lung cell culture supernatants. Taken together, diverse disease-relevant autoreactive B cells, including cells specific for DNA, MPO, and basement membrane, are recruited to lung ectopic lymphoid aggregates in response to cSiO2 instillation. B cells that escape tolerance can contribute to local autoantibody production. Our demonstration of significantly enhanced autoantibody induction by TLR ligands further suggests that a coordinated environmental co-exposure can magnify autoimmune vulnerability.
Sulforaphane diminishes moonlighting of pyruvate kinase M2 and interleukin 1β expression in M1 (LPS) macrophages
Authors: Bahiraii Sheyda , Brenner Martin , Yan Fangfang , Weckwerth Wolfram , Heiss Elke H.
Published: August 2022

Murine macrophages activated by the Toll-like receptor 4 agonist lipopolysaccharide (LPS) polarize to the M1 type by inducing proinflammatory marker proteins and changing their energy metabolism to increased aerobic glycolysis and reduced respiration. We here show that the aliphatic isothiocyanate sulforaphane (Sfn) diminishes M1 marker expression (IL-1β, IL-6, TNF-α, iNOS, NO, and ROS) and leads to highly energetic cells characterized by both high glycolytic and high respiratory activity as assessed by extracellular flux analysis. Focusing on a potential connection between high glycolytic activity and low IL-1β expression in M1 (LPS/Sfn) macrophages, we reveal that Sfn impedes the moonlighting function of pyruvate kinase M2 (PKM2) in M1 macrophages. Sfn limits mono/dimerization and nuclear residence of PKM2 accompanied by reduced HIF-1α levels, Stat3 phosphorylation at tyrosine 705, and IL-1β expression while preserving high levels of cytosolic PKM2 tetramer with high glycolytic enzyme activity. Sfn prevents glutathionylation of PKM2 in LPS-stimulated macrophages which may account for the reduced loss of PKM2 tetramer. Overall, we uncover PKM2 as a novel affected hub within the anti-inflammatory activity profile of Sfn.
Comparison of different assays for the detection of anticyclic citrullinated peptide antibodies in patients with rheumatoid arthritis
Authors: Ma Lisha , Wang Wensheng , Li Lisha , Chen Ying , Chen Binxuan , Shao Miaoli , Cheng Yongjun , Zhou Renfang
Published: August 2022

Objective

To evaluate a novel fully automated immunoturbidimetric assay developed by Qiangsheng Biotechnology Company for the detection of anticyclic citrullinated peptide antibodies (anti-CCP) in serum of patients with rheumatoid arthritis (RA) and compare it to the conventional EUROIMMUN- anti-CCP ELISA. Two other commonly used automated assays, the Elecsys anti-CCP assay, an ECLIA that is run on the Modular Analystics E170 (Cobas Diagnostics, Germany), and an anti-CCP CLIA developed by YHLO that is run on the iFlash 3000 Chemiluminescence Immunoassay Analyzer, were included as reference standards.

Methods

A total of 264 serum samples were collected from patients attending the First People’s Hospital of Wenling affiliated to Wenzhou Medical University between July 2020 and November 2020. These included 131 serum samples collected from patients with RA, 70 serum samples collected from patients with other autoimmune diseases, and 63 serum samples collected from healthy controls at a physical examination. The clinical performance and sensitivity and specificity of the four anti-CCP assays for the diagnosis of RA were compared using receiver operating characteristic (ROC) curve analysis.

Results

The Kappa statistic indicated almost perfect agreement between the EUROIMMUN-anti-CCP ELISA and the Elecsys anti-CCP ECLIA (Cobas) (0.863), the EUROIMMUN-anti-CCP ELISA and the anti-CCP CLIA (YHLO) (0.862), and the Elecsys anti-CCP ECLIA (Cobas) and the anti-CCP CLIA (YHLO) (0.816). On ROC curve analysis, AUC values were 0.955 for the EUROIMMUN-anti-CCP ELISA, 0.948 for the anti-CCP CLIA (YHLO), 0.947 for the Elecsys anti-CCP ECLIA (Cobas) and 0.903 for Qiangsheng, indicating all the assays had a good diagnostic performance for RA.

Conclusion

The anti-CCP assays provided similar diagnostic information. The novel fully automated immunoturbidimetric assay for anti-CCP developed by Qiangsheng Biotechnology Company may be especially useful for large scale clinical screening in RA as it has a shorter testing time than the commercially available alternatives.
CpG content in the Zika virus genome affects infection phenotypes in the adult brain and fetal lymph nodes
Authors: Udenze Daniel , Trus Ivan , Berube Nathalie , Karniychuk Uladzimir
Published: August 2022

Increasing the number of CpG dinucleotides in RNA viral genomes, while preserving the original amino acid composition, leads to impaired infection which does not cause disease. Beneficially, impaired infection evokes antiviral host immune responses providing a cutting-edge vaccine approach. For example, we previously showed that CpG-enriched Zika virus variants cause attenuated infection phenotypes and protect against lethal challenge in mice. While CpG recoding is an emerging and promising vaccine approach, little is known about infection phenotypes caused by recoded viruses in vivo, particularly in non-rodent species. Here, we used well-established mouse and porcine models to study infection phenotypes of the CpG-enriched neurotropic and congenital virus—Zika virus, directly in the target tissues—the brain and placenta. Specifically, we used the uttermost challenge and directly injected mice intracerebrally to compare infection phenotypes caused by wild-type and two CpG-recoded Zika variants and model the scenario where vaccine strains breach the blood-brain barrier. Also, we directly injected porcine fetuses to compare in utero infection phenotypes and model the scenario where recoded vaccine strains breach the placental barrier. While overall infection kinetics were comparable between wild-type and recoded virus variants, we found convergent phenotypical differences characterized by reduced pathology in the mouse brain and reduced replication of CpG-enriched variants in fetal lymph nodes. Next, using next-generation sequencing for the whole virus genome, we compared the stability of de novo introduced CpG dinucleotides during prolonged virus infection in the brain and placenta. Most de novo introduced CpG dinucleotides were preserved in sequences of recoded Zika viruses showing the stability of vaccine variants. Altogether, our study emphasized further directions to fine-tune the CpG recoding vaccine approach for better safety and can inform future immunization strategies.
Neutrophil heterogeneity in complement C1q expression associated with sepsis mortality
Authors: Trzeciak Alissa , Mongre Raj Kumar , Kim Ma Rie , Lim Kihong , Madero Rafael A. , Parkhurst Christopher N. , Pietropaoli Anthony P. , Kim Minsoo
Published: August 2022

Sepsis is a life-threatening systemic inflammatory condition causing approximately 11 million annual deaths worldwide. Although key hyperinflammation-based organ dysfunctions that drive disease pathology have been recognized, our understanding of the factors that predispose patients to septic mortality is limited. Due to the lack of reliable prognostic measures, the development of appropriate clinical management that improves patient survival remains challenging. Here, we discovered that a subpopulation of CD49chigh neutrophils with dramatic upregulation of the complement component 1q (C1q) gene expression arises during severe sepsis. We further found that deceased septic patients failed to maintain C1q protein expression in their neutrophils, whereas septic survivors expressed higher levels of C1q. In mouse sepsis models, blocking C1q with neutralizing antibodies or conditionally knocking out C1q in neutrophils led to a significant increase in septic mortality. Apoptotic neutrophils release C1q to control their own clearance in critically injured organs during sepsis; thus, treatment of septic mice with C1q drastically increased survival. These results suggest that neutrophil C1q is a reliable prognostic biomarker of septic mortality and a potential novel therapeutic target for the treatment of sepsis.
The HMGB1 (C106A) mutation inhibits IL-10-producing CD19hiFcγRIIbhi B cell expansion by suppressing STAT3 activation in mice
Authors: Liu Mengru , Zhou Jingwen , Yin Rui , Yin Hui , Ding Yue , Ma Feng , Qian Li
Published: August 2022

Regulatory B cells have important roles in inflammation and autoimmune diseases. A newly discovered subpopulation of B cells with a CD19hiFcγRIIbhi phenotype inhibits the proliferation of CD4+ T cells by secreting interleukin (IL)-10. The expansion of CD19hiFcγRIIbhi B cells in mouse spleen can be induced by lipopolysaccharide (LPS) or CpG oligodeoxynucleotide stimulation. However, the mechanism of CD19hiFcγRIIbhi B cell expansion and its role in inflammatory diseases are unclear. Here, we report that, under inflammatory conditions, the proliferation and immunosuppressive function of CD19hiFcγRIIbhi B cells were decreased in high mobility group box1 (HMGB1) C106A mutant mice, compared with wild-type mice. The HMGB1 (C106A) mutation in B cells reduced STAT3 phosphorylation, restricting the expansion and suppressive function of CD19hiFcγRIIbhi B cells. Compared with CD19hiFcγRIIbhi B cells from wild-type mice, CD19hiFcγRIIbhi B cells from Hmgb1(C106A) mice significantly reduced the survival of mice with sepsis. Recombinant HMGB1 promoted the expansion of IL-10-producing CD19hiFcγRIIbhi B cells among LPS-activated B cells in vitro. Furthermore, the percentage of CD19hiFcγRIIbhi regulatory B cells in the peripheral blood was increased in patients with sepsis, compared with healthy controls. These findings implicate the role of HMGB1 in the expansion and immunosuppressive function of CD19hiFcγRIIbhi B cells.
Persistently High Incidences of Trypanosoma brucei rhodesiense Sleeping Sickness With Contrasting Focus-Dependent Clinical Phenotypes in Malawi
Authors: Nambala Peter , Mulindwa Julius , Chammudzi Priscilla , Senga Edward , Lemelani Marshal , Zgambo Drifton , Matovu Enock , MacLeod Annette , Musaya Janelisa
Published: August 2022

Background

Human African trypanosomiasis (HAT) has caused social–economic burden in remote rural communities mostly in sub-Saharan Africa for over a century. The World Health Organization had targeted the year 2020 for the elimination of HAT caused by Trypanosoma brucei rhodesiense, which is mainly endemic in Malawi, Uganda, Tanzania, and Zambia. Significant progress has been made in reducing reported HAT cases in some countries. Area-specific updated epidemiological and clinical data may facilitate in understanding the progress of such efforts as well as the development of new intervention strategies.

Methods

We analyzed HAT prevalence and demographics from epidemiological surveys carried out from 2012 to 2020 obtained from the Ministry of Health, Malawi. In addition, we analyzed blood samples and clinical profiles of HAT patients surveyed between 2016 and 2020 from Rumphi and Nkhotakota districts. From the blood samples, parasite observations and speciation were carried out, whereas disease staging and severity were ascertained from the clinical profiles.

Results

Malawi reported 315 HAT cases from 2012 to 2020. The majority of HAT cases were men (70.2%), and the mean age was 29.9 ± 15.3 with all HAT fatalities resulting from stage 2 disease. Clinical symptoms were not significantly associated with disease outcome; however, swollen lymph nodes (p = 0.004), weight loss (p = 0.010), headache (p = 0.019), and sleep disturbance (p = 0.032) were significantly associated with the HAT stage of patients. About 50% of all HAT patients were reported within 2 years from 2019 to 2020, suggesting a HAT outbreak in Malawi.

Conclusion

This study has highlighted the current epidemiological insights of the rHAT trend in Malawi. We have shown that rHAT clinical phenotypes in Malawi are focus-dependent and that there has been a steady increase in rHAT cases compared to all countries with incidences of rHAT. We have also highlighted an outbreak of rHAT that occurred in Malawi from 2019 to 2020 with almost 50% of the total rHAT cases that we have presented in this study reported within 2 years of the outbreak. These should call for a review of Malawi’s rHAT control and elimination strategies. A One-Health approach with the inclusion of key stakeholders such as the department of parks and wildlife may also be considered.
Detection of Habitat Shifts of Cetacean Species: A Comparison Between 2010 and 2017 Habitat Suitability Conditions in the Northwest Atlantic Ocean
Authors: Chavez-Rosales Samuel , Josephson Elizabeth , Palka Debra , Garrison Lance
Published: August 2022

The simultaneous effects of human activities in the ocean and climate change have already produced a series of responses from the marine ecosystems. With the potential increment of future human activities, such as offshore renewable energy developments, proactive management is required. To facilitate effective management and conservation actions, it is imperative to identify species potentially at risk and their critical habitats. Here we examine 16 cetacean species habitat suitability in the western North Atlantic Ocean using generalized additive models developed from data collected by NOAA- Northeast and Southeast Fisheries Science Centers from 2010 to 2017. The models were based on observed species distribution as a function of 21 environmental covariates and compare species-specific core habitats between 2010 and 2017. We identified seasonal differences in patterns of habitat change across guilds and an average northward shift of 178 km across the study area. The effects of these shifts are still unknown, but for already stressed species, the contraction or displacement of their historical habitat could worsen their population status. Therefore, the imminent development of offshore regions, in addition to the effects of climate change emphasize the need of adaptively managing ecosystems on the face of multiple challenges.
Coral bleaching from a nutrient perspective is understudied: A bibliometric survey
Authors: Li Tangcheng , Huang Jiahong , Du Hong , Liu Xiaojuan , Zhong Chongming , Lin Senjie
Published: August 2022

How coral–Symbiodiniaceae mutualistic symbiosis is established, maintained, and disrupted is arguably the most fundamental and central area of coral research. The breakdown of this symbiosis, and consequent coral bleaching, have been frequently attributed to thermal stress, although microbial attack and pollution have also been blamed. Despite the perceived intense and broad research, it is unclear whether all the potential causes have been given adequate attention and whether some important areas have been overlooked. This work aims to comprehensively review the literature on coral and Symbiodiniaceae research and provide a portrait of the current coral research landscape, hence identifying areas that require more research effort. Data of publication output were extracted from the Web of Science (WoS) from 1986 to 2022 by using the keywords “coral” and “Symbiodiniaceae.” A total of 43,089 and 3,191 papers in the coral and Symbiodiniaceae were identified, mostly published after 2002. The journal Coral Reefs was ranked first regarding the total number of publications on coral or Symbiodiniaceae. The USA, Australia, and China were the top three countries in the number of publications. The network co-occurrence analysis of all keywords in coral and Symbiodiniaceae using VOSviewer showed that biodiversity, climate change, nutrient, and survival were the central research areas in coral and Symbiodiniaceae. Among them, climate change was the most invested research field, as revealed by the high proportion of published literature, while nutrient was the most understudied area. Thematic evolution analysis revealed that nutrient enrichment combined with elevated temperature was an emerging research field about coral and Symbiodiniaceae. Besides, nitrogen is currently the most studied nutrient. The findings from this study shed light on the trends of coral and Symbiodiniaceae research in the past 36 years, current research hotspots in the field, and areas that need more research investment going forward.
Accelerating Species Recognition and Labelling of Fish From Underwater Video With Machine-Assisted Deep Learning
Authors: Marrable Daniel , Barker Kathryn , Tippaya Sawitchaya , Wyatt Mathew , Bainbridge Scott , Stowar Marcus , Larke Jason
Published: August 2022

Machine-assisted object detection and classification of fish species from Baited Remote Underwater Video Station (BRUVS) surveys using deep learning algorithms presents an opportunity for optimising analysis time and rapid reporting of marine ecosystem statuses. Training object detection algorithms for BRUVS analysis presents significant challenges: the model requires training datasets with bounding boxes already applied identifying the location of all fish individuals in a scene, and it requires training datasets identifying species with labels. In both cases, substantial volumes of data are required and this is currently a manual, labour-intensive process, resulting in a paucity of the labelled data currently required for training object detection models for species detection. Here, we present a “machine-assisted” approach for i) a generalised model to automate the application of bounding boxes to any underwater environment containing fish and ii) fish detection and classification to species identification level, up to 12 target species. A catch-all “fish” classification is applied to fish individuals that remain unidentified due to a lack of available training and validation data. Machine-assisted bounding box annotation was shown to detect and label fish on out-of-sample datasets with a recall between 0.70 and 0.89 and automated labelling of 12 targeted species with an F1 score of 0.79. On average, 12% of fish were given a bounding box with species labels and 88% of fish were located and given a fish label and identified for manual labelling. Taking a combined, machine-assisted approach presents a significant advancement towards the applied use of deep learning for fish species detection in fish analysis and workflows and has potential for future fish ecologist uptake if integrated into video analysis software. Manual labelling and classification effort is still required, and a community effort to address the limitation presented by a severe paucity of training data would improve automation accuracy and encourage increased uptake.
Transcriptomic analysis reveals yolk accumulation mechanism from the hepatopancreas to ovary in the pacific white shrimp Litopenaeus vannamei
Authors: Li Zhi , Zhou Minyu , Ruan Yao , Chen Xiaoli , Ren Chunhua , Yang Hao , Zhang Xin , Liu Jinshang , Li Huo , Zhang Lvping , Hu Chaoqun , Chen Ting , Wu Xugan
Published: August 2022

The Pacific white shrimp Litopenaeus vannamei is an economically important penaeid species worldwide. Under farming conditions, the full ovarian maturation of L. vannamei generally depends on the combination of artificial ablation of unilateral eyestalk and feeding high-quality natural diets, suggesting that nutrient accumulation is important to ovarian maturation. In this study, we aimed to investigate the gene expression related to nutritional accumulation in L. vannamei during ovarian development by transcriptomic analysis. A total of 52.45 Gb of high-quality transcriptome data were obtained from 8 samples from the hepatopancreas and ovaries from shrimp in gonadal developmental stages I-IV. A total of 23,149 expressed genes were detected, of which 19,852 were known genes and 3,297 were novel genes. Our study found that genes related to amino acid, carbohydrate and lipid metabolism were expressed at higher levels in the hepatopancreas than in the ovary. The genes for most lipoproteins and their receptors were predominantly expressed in the hepatopancreas, while vitellogenin receptor (VgR) was specifically expressed in the ovary. Moreover, two vitellogenin (Vg) genes were identified, in which one was specifically expressed in the hepatopancreas and defined as Hp-Vg, and the other was specifically expressed in the ovary and defined as Ov-Vg. In addition, genes related to carotenoid metabolism were enriched in the hepatopancreas. This study provides solid evidence that the hepatopancreas is the major exogenous vitellogenesis site for ovarian maturation of L. vannamei. Two distinct Vg genes perform exogenous and endogenous vitellogenesis in the hepatopancreas and ovary in L. vannamei, respectively. The results of this study also presented some new insights for understanding the nutritional dynamics from the hepatopancreas to ovary during ovarian maturation in penaeids.
Chemical and genomic analyses of a marine-derived Streptomyces sp. V17-9 producing amino acid derivatives and siderophores
Authors: Kim Da-Eun , Hong Sung-Chul , Yang Yoonyong , Choi Jaeyoung , Park Jin-Soo
Published: August 2022

Streptomyces, the largest genus in Actinobacteria, has been known as a chemically prolific bacterial group producing pharmaceutically important small molecules. Various endeavors have been made to discover novel secondary metabolites from strains inhabiting diverse environmental niches. In our course of collecting bacterial strains to discover biologically active molecules, a marine-derived Streptomyces sp. V17-9 was isolated from a seagrass collected from a beach on Côn Đảo, Vietnam. Phylogenetic and genomic analyses suggested the possibility that this strain might form a new taxonomic group with a few closely related unclassified strains. The genome sequence of strain V17-9 was predicted to have 20 putative biosynthetic gene clusters. A chemical investigation identified amino acid derivatives (N-acetyltryptamine, N-acetyltyramine, and 6-prenyltryptophol) and siderophores (desferrioxamine E and spoxazomicin A) from culture extracts, linking gene clusters with actual productions. In particular, prenylated indole compounds were enhanced in production as part of metabolic conversion under supplement with ferric ions. Sequence similarity networks for indole and siderophore gene clusters showed their diversity and complexity in the genus Streptomyces. Phylogenomic analysis of gene cluster for 6-prenyltryptophol suggested strains of genomic potential for production of such compounds. They also suggested how these gene clusters may have shaped the biosynthesis of natural products. Chemotaxonomic profiling coupled with genome analysis would provide new insights into comparative studies on Actinobacteria producing prenylated indoles and siderophores.
Intertidal intercepted sediment at jetties along the Gulf of Thailand
Authors: Saengsupavanich Cherdvong , Yun Lee Shin , Lee Lee Hin , Sanitwong-Na-Ayutthaya Sarinya
Published: August 2022

Sand bypassing is one of the promising solutions to rectify jetty-induced coastal erosion. Estimating alongshore sediment transport rate and understanding hydrodynamic conditions at a jetty are crucial for successful downdrift erosion management. This research investigated three major jetties in Thailand (Cha Am jetty, Krai jetty, and Na Saton jetty) that protrude across the surf zone and completely intercept alongshore sediment transport. Sub-aerial and inter-tidal field surveys by Real Time Kinematic (RTK) technique were undertaken in 2019 and 2020. The collected data was processed and overlaid to calculate the amount of sediment deposition at the updrift jetty. Numerical simulations using MIKE21 SW and MIKE21 HD were carried out in order to understand how waves and water currents interacted with the jetties. From the results, we found that the Cha Am jetty trapped approximately 38,187 cu.m/yr of the alongshore sediment. While the Krai jetty intercepted approximately 34,170 cu.m/yr of the alongshore drift, and approximately 65,951 cu.m/yr of longshore sediment transport was blocked by the Na Saton jetty. Such estimated amounts of deposited sediment are the quantities that should be bypassed at each jetty. Budgets and implementation plans for sand bypassing can be prepared. Decision makers can decide how to manage updrift deposition and downdrift erosion.
Cross-Front Transport Triggered by Winter Storms Around the Shandong Peninsula, China
Authors: Xu Xiaomei , Gao Jianhua , Shi Yong , Wu Xiaodong , Lv Jixuan , Zhang Shuo , Liu Shengjing , Liu Tao , Yang Guang
Published: August 2022

Ocean fronts are widespread on the eastern China shelf, especially in winter and early spring. Previous studies have shown that sediments on the northern coast of the Shandong Peninsula could penetrate the coastal fronts and deposit on the southern coast of the Liaodong Peninsula, and this cross-front transport process is closely related to winter storms. However, the detailed mechanisms of cross-front transport remain unclear. In this study, through realistic numerical modeling and physical mechanism analysis, a dynamic mechanism involving cross-front transport triggered by winter storms was proposed, and two locations with the highest probability of frontal instability around the Shandong Peninsula were identified. In detail, forced by winter storms, the Lubei Coastal Current significantly intensifies first and causes frontal inertial instability in the early stage of the winter storm, favoring cross-front exchange between both sides of the front. Then, serving as a compensation current, the Yellow Sea Warm Current intensifies in the late stage of the winter storm, leading to the northward transport of the materials out of the front. Furthermore, the intensity, distance, and path of the cross-front transport under varying winter storms are also investigated. The winter storm, with longer duration, greater wind speed, and westward wind direction, tends to trigger stronger cross-front transport and longer transport distance. Transport paths also differ under different winter storms. This study provides a theoretical explanation for cross-front transport and analyzes the role of winter storms in it, providing some new ideas for nearshore materials dispersal to the sea, which is of great significance for future studies on pollutant diffusion, nutrient distribution, and sediment transport in coastal areas.
POF (paclitaxel/oxaliplatin/5-fluorouracil/leucovorin) vs. SOX/CAPOX/FOLFOX as a postoperative adjuvant chemotherapy for curatively resected stage III gastric cancer: Study protocol for a randomized controlled trial, FNF-014 trial
Authors: Su Liyu , Zhao Shen , Yin Yi , Huang Feng , Zhu Jinfeng , Chen Luchuan ,   FNF Independent Investigations Group, Lin Rongbo
Published: August 2022

Background

Postoperative chemotherapy is a standard treatment for stage II and III gastric cancer in Asia. With regard to single-agent or doublet, the need for improvement has consistently been pointed out because of the relatively poor outcome for patients with stage III gastric cancer. Triplet has shown significant survival benefits in the perioperative setting. We conducted a randomized, multicenter, phase III study to compare triplet to doublet regimens for patients with stage III gastric cancer.

Methods

This is currently enrolling patients (n = 230) with pathologic stage III gastric cancer after D2 lymph node dissection and achieved R0 resection. Patients are randomized 1:1 and stratified by tumor stage (IIIA, IIIB, or IIIC, AJCC 8th) into POF or SOX/CAPOX/FOLFOX. S-1 and oxaliplatin (SOX): oxaliplatin 130 mg/m2 on day 1, oral S-1 80–120 mg/m2 divided by two on days 1–14 every 21 days for 8 cycles. Capecitabine and oxaliplatin (CAPOX): oxaliplatin 130 mg/m2 on day 1, oral capecitabine 1000 mg/m2 twice daily on days 1–14 every 21 days for 8 cycles. Folinic acid (or leucovorin), 5-fluorouracil and oxaliplatin (FOLFOX): oxaliplatin 85 mg/m2, levo-leucovorin 200 mg/m2, and 5-fluorouracil (5-FU) 400 mg/m2 bolus on day 1, then 5-FU 2400 mg/m2 continuous infusion over 46 h, every 14 days for 12 cycles. Three doublets were chosen by the clinicians. Paclitaxel, oxaliplatin, 5-fluorouracil, and leucovorin (POF): paclitaxel 135 mg/m2, followed by FOLFOX omitted 5-FU bolus, every 14 days for 12 cycles. The primary end point is 3-year disease-free survival (3-year-DFS). Secondary end points are overall survival (OS) and safety (any adverse event).

Discussion

The results of this study will help establish postoperative clinical evidence for patients with locally advanced gastric adenocarcinoma or gastroesophageal junction adenocarcinoma.

Clinical Trial Registration

[www.ClinicalTrials.gov], identifier [NCT0378826].
Dynamic serum albumin and outcome of peritoneal dialysis patients: A retrospective study in China
Authors: Song Panai , Yang Dong , Li Jine , Zhuo Ning , Fu Xiao , Zhang Lei , Zhang Hongqing , Liu Hong , Sun Lin , Liu Yinghong
Published: August 2022

Introduction

Serum albumin levels at a single time point have been shown to predict mortality in peritoneal dialysis (PD) patients. However, we believe that the dynamic change in albumin after PD may be more significant. In this study, we investigated the relationship between dynamic serum albumin and the clinical outcome of patients undergoing continuous ambulatory peritoneal dialysis (CAPD).

Methods

The participants in this study enrolled 586 patients who underwent CAPD at the peritoneal dialysis center of Second Xiangya Hospital in China. We retrospectively reviewed medical records from January 1, 2010, to December 31, 2019. Baseline serum albumin (Alb), time-averaged albumin level (TA-ALB) and serum albumin reach rate (SR: defined as the percentage of serum albumin measurements that reached ≥ 35 g/L) were applied as the predictor variables. All-cause mortality and cardiovascular mortality were used as the outcome variables. Hazard function of all-cause mortality and cardiovascular mortality in the study participants were examined by using Cox proportional hazard regression models.

Results

Age (HR = 1.03, 95% CI 1.00–1.05), cardiovascular disease (HR = 1.80, 95% CI 1.07–3.03) and TA-ALB (HR = 0.92, 95% CI 0.85–0.99) were independent risk factors for all-cause mortality in PD patients. Patients with TA-ALB of <33 g/L (HR = 2.33, 95% CI 1.17–4.62) exhibited a higher risk for all-cause mortality than those with TA-ALB ≥ 36 g/L. Stratified SR showed a similar trend. Patients with a <25% SR exhibited a significantly increased risk for all-cause mortality (HR = 2.72, 95% CI, 1.24–5.96) by fully adjusted analysis. However, neither TA-ALB nor SR were associated with the risk of cardiovascular mortality after adjusted analysis.

Conclusion

This study demonstrated that age, cardiovascular disease, and TA-ALB were independent risk factors for all-cause mortality in PD patients. TA-ALB and SR can better predict the prognosis of PD patients than baseline Alb. Dynamic changes in Alb are more clinically significant than baseline Alb in predicting mortality risk.