bluuebunny/crossref_metadata_2025 huggingface dataset:
The roles of different forms of IL-15 in human melanoma progression
Authors: Di Matteo Sabina , Munari Enrico , Fiore Piera Filomena , Santopolo Silvia , Sampaoli Camilla , Pelosi Andrea , Chouaib Salem , Tumino Nicola , Vacca Paola , Mariotti Francesca Romana , Ebert Stefan , Machwirth Markus , Haas Dorothee , Pezzullo Marco , Pietra Gabriella , Grottoli Melania , Buart Stephanie , Mortier Erwan , Maggi Enrico , Moretta Lorenzo , Caruana Ignazio , Azzarone Bruno
Published: June 2023

Background

Melanoma is a lethal skin cancer, and the risk of developing it is increased by exposure to ultraviolet (UV) radiation. The production of cytokines such as interleukin-15 (IL-15), induced by the exposure of skin cells to UV rays, could also promote melanoma development. The aim of this study is to investigate the possible role of Interleukin-15/Interleukin-15 Receptor α (IL-15/IL-15Rα) complexes in melanoma development.

Methods

The expression of IL-15/IL-15Rα complexes by melanoma cells was evaluated both ex vivo and in vitro by tissue microarray, PCR, and flow cytometry. The presence of the soluble complex (sIL-15/IL-15Rα) in the plasma of metastatic melanoma patients was detected using an ELISA assay. Subsequently, we investigated the impact of natural killer (NK) cell activation after rIL-2 starvation followed by exposure to the sIL-15/IL-15Rα complex. Finally, by analyzing public datasets, we studied the correlation between IL-15 and IL-15Rα expressions and melanoma stage, NK and T-cell markers, and overall survival (OS).

Results

Analysis of a melanoma tissue microarray shows a significant increase in the number of IL-15+ tumor cells from the benign nevi to metastatic melanoma stages. Metastatic melanoma cell lines express a phorbol-12-myristate-13-acetate (PMA)-cleavable membrane-bound IL-15 (mbIL-15), whereas cultures from primary melanomas express a PMA-resistant isoform. Further analysis revealed that 26% of metastatic patients present with consistently high plasmatic levels of sIL-15/IL-15Rα. When the recombinant soluble human IL-15/IL-15Rα complex is added to briefly starved rIL-2-expanded NK cells, these cells exhibit strongly reduced proliferation and levels of cytotoxic activity against K-562 and NALM-18 target cells. The analysis of public gene expression datasets revealed that high IL-15 and IL-15Rα intra-tumoral production correlates with the high levels of expression of CD5+ and NKp46+ (T and NK markers) and significantly correlates with a better OS in stages II and III, but not in stage IV.

Conclusions

Membrane-bound and secreted IL-15/IL-15Rα complexes are continuously present during progression in melanoma. It is notable that, although IL-15/IL-15Rα initially promoted the production of cytotoxic T and NK cells, at stage IV promotion of the development of anergic and dysfunctional cytotoxic NK cells was observed. In a subgroup of melanoma metastatic patients, the continuous secretion of high amounts of the soluble complex could represent a novel NK cell immune escape mechanism.
Increasing human monoclonal antibody cloning efficiency with a whole-cell modified immunoglobulin-capture assay (mICA)
Authors: Siris Sara , Gladstone Camilla A. , Guo Yanping , Patel Radhika , Pinder Christopher L. , Shattock Robin J. , McKay Paul F. , Langford Paul R. , Bidmos Fadil A.
Published: June 2023

Expression cloning of fully human monoclonal antibodies (hmAbs) is seeing powerful utility in the field of vaccinology, especially for elucidating vaccine-induced B-cell responses and novel vaccine candidate antigen discovery. Precision of the hmAb cloning process relies on efficient isolation of hmAb-producing plasmablasts of interest. Previously, a novel immunoglobulin-capture assay (ICA) was developed, using single protein vaccine antigens, to enhance the pathogen-specific hmAb cloning output. Here, we report a novel modification of this single-antigen ICA using formalin-treated, fluorescently stained whole cell suspensions of the human bacterial invasive pathogens, Streptococcus pneumoniae and Neisseria meningitidis. Sequestration of IgG secreted by individual vaccine antigen-specific plasmablasts was achieved by the formation of an anti-CD45-streptavidin and biotin anti-IgG scaffold. Suspensions containing heterologous pneumococcal and meningococcal strains were then used to enrich for polysaccharide- and protein antigen-specific plasmablasts, respectively, during single cell sorting. Following application of the modified whole-cell ICA (mICA), ~61% (19/31) of anti-pneumococcal polysaccharide hmAbs were cloned compared to 14% (8/59) obtained using standard (non-mICA) methods – representing a ~4.4-fold increase in hmAb cloning precision. A more modest ~1.7-fold difference was obtained for anti-meningococcal vaccine hmAb cloning; ~88% of hmAbs cloned via mICA versus ~53% cloned via the standard method were specific for a meningococcal surface protein. VDJ sequencing revealed that cloned hmAbs reflected an anamnestic response to both pneumococcal and meningococcal vaccines; diversification within hmAb clones occurred by positive selection for replacement mutations. Thus, we have shown successful utilization of whole bacterial cells in the ICA protocol enabling isolation of hmAbs targeting multiple disparate epitopes, thereby increasing the power of approaches such as reverse vaccinology 2.0 (RV 2.0) for bacterial vaccine antigen discovery.
Interferon-gamma ameliorates experimental autoimmune encephalomyelitis by inducing homeostatic adaptation of microglia
Authors: Tichauer Juan E. , Arellano Gabriel , Acuña Eric , González Luis F. , Kannaiyan Nirmal R. , Murgas Paola , Panadero-Medianero Concepción , Ibañez-Vega Jorge , Burgos Paula I. , Loda Eileah , Miller Stephen D. , Rossner Moritz J. , Gebicke-Haerter Peter J. , Naves Rodrigo
Published: June 2023

Compelling evidence has shown that interferon (IFN)-γ has dual effects in multiple sclerosis and in its animal model of experimental autoimmune encephalomyelitis (EAE), with results supporting both a pathogenic and beneficial function. However, the mechanisms whereby IFN-γ may promote neuroprotection in EAE and its effects on central nervous system (CNS)-resident cells have remained an enigma for more than 30 years. In this study, the impact of IFN-γ at the peak of EAE, its effects on CNS infiltrating myeloid cells (MC) and microglia (MG), and the underlying cellular and molecular mechanisms were investigated. IFN-γ administration resulted in disease amelioration and attenuation of neuroinflammation associated with significantly lower frequencies of CNS CD11b+ myeloid cells and less infiltration of inflammatory cells and demyelination. A significant reduction in activated MG and enhanced resting MG was determined by flow cytometry and immunohistrochemistry. Primary MC/MG cultures obtained from the spinal cord of IFN-γ-treated EAE mice that were ex vivo re-stimulated with a low dose (1 ng/ml) of IFN-γ and neuroantigen, promoted a significantly higher induction of CD4+ regulatory T (Treg) cells associated with increased transforming growth factor (TGF)-β secretion. Additionally, IFN-γ-treated primary MC/MG cultures produced significantly lower nitrite in response to LPS challenge than control MC/MG. IFN-γ-treated EAE mice had a significantly higher frequency of CX3CR1high MC/MG and expressed lower levels of program death ligand 1 (PD-L1) than PBS-treated mice. Most CX3CR1highPD-L1lowCD11b+Ly6G- cells expressed MG markers (Tmem119, Sall2, and P2ry12), indicating that they represented an enriched MG subset (CX3CR1highPD-L1low MG). Amelioration of clinical symptoms and induction of CX3CR1highPD-L1low MG by IFN-γ were dependent on STAT-1. RNA-seq analyses revealed that in vivo treatment with IFN-γ promoted the induction of homeostatic CX3CR1highPD-L1low MG, upregulating the expression of genes associated with tolerogenic and anti-inflammatory roles and down-regulating pro-inflammatory genes. These analyses highlight the master role that IFN-γ plays in regulating microglial activity and provide new insights into the cellular and molecular mechanisms involved in the therapeutic activity of IFN-γ in EAE.
Case Report: Imaging immune checkpoint inhibitor-induced yin-yang effects in the brain
Authors: Bol K. F. , Peeters E. , van Herpen C. M. L. , Westdorp H. , Aarntzen E. H. J. G.
Published: June 2023

Background

Treatment with immune checkpoint inhibitors (ICI) can induce durable responses in cancer patients, but it is commonly associated with serious immune-related side effects. Both effects are suggested to be mediated by CD8+ T-cell infiltration. Whole body CD8+ T-cell distribution can be visualized by PET imaging of a 89Zr-labeled anti-humanCD8a minibody, currently investigated in a phase 2b trial.

Main body

An adult patient diagnosed with metastatic melanoma developed ICI-related hypophysitis after two courses of combined immunotherapy (ipilimumab (3 mg/kg) and nivolumab (1 mg/kg) at 3 weeks interval). On a [89Zr]Zr-crefmirlimab berdoxam PET/CT scan, made 8 days before clinical symptoms occurred, increased CD8+ T-cell infiltration in the pituitary gland was detected. Simultaneously, tracer uptake in a cerebral metastasis was increased, indicating ICI-induced tumor infiltration by CD8+ T-cells.

Conclusions

The observations in this case report underscore the role of CD8+ T-cell in non-tumor tissues in ICI-related toxicity. In addition, it illustrates a potential role for molecular imaging by PET/CT for investigation and monitoring of ICI-induced effects.
Cryptic genetic diversity and associated ecological differences of Anastatus orientalis, an egg parasitoid of the spotted lanternfly
Authors: Wu Yunke , Broadley Hannah J. , Vieira Kendra A. , McCormack John J. , Losch Corrine A. , Namgung Hyeban , Kim Yeongmo , Kim Hyojoong , McGraw Alana R. , Palmeri Marjorie Z. , Lee Seunghwan , Cao Liangming , Wang Xiaoyi , Gould Juli R.
Published: June 2023

Anastatus orientalis, native to northern China, is an egg parasitoid wasp of the spotted lanternfly (Lycorma delicatula) and is being tested as a potential biological control agent for invasive L. delicatula in the United States. As a component of these evaluations, live A. orientalis collected from Beijing and Yantai in China were reared in containment in the U.S. These specimens showed different responses in diapause behaviors to rearing conditions used previously by other researchers. To understand the primary mechanism potentially driving discrepancies in important life history traits, we used molecular tools to examine the genetic composition of A. orientalis from China and from South Korea, where the parasitoid has been introduced to aid in the population management of invasive L. delicatula. Molecular analysis of mitochondrial DNA recovered six haplotype groups, which exhibit biased frequency of abundance between collection sites. Some haplotypes are widespread, and others only occur in certain locations. No apparent pattern is observed between wasps collected from different years or emergence seasons. Uncorrected genetic distances between haplotype groups range from 0.44% to 1.44% after controlling for within-group variation. Genetic variance of A. orientalis is characterized by high levels of local diversity that contrasts with a lack of a broad-scale population structure. The introduced Korean population exhibits lower genetic diversity compared to native populations. Additionally, we created iso-female lines for major haplotype groups through laboratory rearing. Differences in diapause behavior were correlated with mitochondrial haplotype. Our results indicate that the observed life history traits in A. orientalis have a genetic base.
Problems identification and improvement path of China’s marine ecological compensation legal system
Authors: Wang Tao
Published: June 2023

In China’s marine industry, which has been growing quickly over the past few years, marine ecological compensation has been a critical framework for safeguarding the marine environment. Through the text analysis of the China’s marine ecological compensation legal system, this study found that there are multiple defects in it, including institutional supply shortage leads to lack of coordination and dispersion in China’s marine ecological compensation legislative system, the absence of legislative concept of ‘land-sea overall planning’ in China’s marine ecological compensation legal system, limited scope of China’s marine ecological compensation, lack of clear standards for marine ecological compensation, the relationship between marine planning and the marine ecological compensation system is not straightforward, and insufficiency of regulation on the marine ecological compensation. The paper suggests that priority should be given to developing a multi-level legal system for compensating marine ecological damage, the legal method of achieving ‘land-sea overall planning’ and a compensation mechanism that combines a variety of compensation methods with a scientific and reasonable standard should be established within China’s ecological compensation legal system, marine ecological compensation should be incorporated into marine planning and the separation of powers and implementation of the marine ecological compensation regulation should be enhanced.
A seasonal circulation index for the ocean and its application to the South China Sea
Authors: Li Qiang , Huang Run Xin , Xie Lingling
Published: June 2023

Ocean circulation is crucial in redistributing mass and energy on Earth. However, it varies significantly on a seasonal time scale due to external forcing. To quantify the seasonality of ocean circulation, we propose a seasonal circulation index (SCI). This index is defined as the normalized maximum deviation from the velocity vector, whose magnitude is the largest in one period. We have substantiated the efficiency of this index using the monsoon wind in the South China Sea (SCS). By utilizing this index, we have obtained the 3D structure of the seasonality of ocean circulation in the SCS. The SCI and the seasonal circulation amplitude (SCA) exhibit large values over 0.9 and 0.8 m s-1 in the western boundary current. Alternating southwest-northeastward bands of SCI with high and low values are distributed from the north shelf to the south, especially in the eastern basin. Although SCA decreases significantly with depth, SCI exhibits values higher than 0.7 in both the middle and deep layers, indicating a noteworthy seasonality and middle-layer enhancement in the abyssal basin of the SCS.
Advances on in situ TEM mechanical testing techniques: a retrospective and perspective view
Authors: Li Keqiang , Bu Yeqiang , Wang Hongtao
Published: June 2023

Over the past few decades, in situ transmission electron microscopy (TEM) has emerged as a powerful experimental technique for materials design and characterization. It offers unparalleled dynamic details of materials deformation under mechanical stimuli, providing fundamental insights into their deformation and failure mechanisms for various materials. In this review, we summarize recent advances on in situ TEM mechanical characterization techniques, including classical tension holders, nanoindentation holders, MEMS devices, thermal bimetallic-based techniques, and nanomanipulation techniques. The advantages and limitations of in situ TEM tests are also discussed. To provide a broader perspective, the article highlights promising opportunities for in situ TEM mechanical testing studies in characterization-processing-manufacturing based on nanomanipulation, ultrafast TEM, electron beam irradiation environmental conditions, data-driven machine learning, and integrated experimental and simulation characterization. This article aims to provide a comprehensive understanding of in situ TEM-based mechanical characterization techniques to promote the development of novel materials with improved mechanical properties for various applications.
A modified Ranson score to predict disease severity, organ failure, pancreatic necrosis, and pancreatic infection in patients with acute pancreatitis
Authors: Luo Xiuping , Wang Jie , Wu Qing , Peng Peng , Liao Guolin , Liang Chenghai , Yang Huiying , Huang Jiean , Qin Mengbin
Published: June 2023

Background

Although there are several scoring systems currently used to predict the severity of acute pancreatitis, each of them has limitations. Determine the accuracy of a modified Ranson score in predicting disease severity and prognosis in patients with acute pancreatitis (AP).

Methods

AP patients admitted or transferred to our institution were allocated to a modeling group (n = 304) or a validation group (n = 192). A modified Ranson score was determined by excluding the fluid sequestration parameter and including the modified computed tomography severity index (CTSI). The diagnostic performance of the modified Ranson score was compared with the Ranson score, modified CTSI, and bedside index of severity in acute pancreatitis (BISAP) score in predicting disease severity, organ failure, pancreatic necrosis and pancreatic infection.

Results

The modified Ranson score had significantly better accuracy that the Ranson score in predicting all four outcome measures in the modeling group and in the validation group (all p < 0.05). For the modeling group the modified Ranson score had the best accuracy for predicting disease severity and organ failure, and second-best accuracy for predicting pancreatic necrosis and pancreatic infection. For the verification group, it had the best accuracy for predicting organ failure, second-best accuracy for predicting disease severity and pancreatic necrosis, and third-best accuracy for predicting pancreatic infection.

Conclusion

The modified Ranson score provided better accuracy than the Ranson score in predicting disease severity, organ failure, pancreatic necrosis and pancreatic infection. Relative to the other scoring systems, the modified Ranson system was superior in predicting organ failure.
Association between obstructive sleep apnea and resistant hypertension: systematic review and meta-analysis
Authors: Ahmed Abass Mahamoud , Nur Salman Mohamud , Xiaochen Yuan
Published: June 2023

Introduction

Obstructive sleep apnea syndrome (OSAS) is a chronic disorder characterized by recurring episode obstruction and collapse of upper airways during sleep, leading to hypoxia and sleep disruption. OSAS is commonly associated with an increased prevalence of hypertension. The underlying mechanism in OSA with hypertension is related to intermittent hypoxia. This hypoxia induces endothelial dysfunction, overactivity of sympathetic effects, oxidative stress, and systemic inflammation. Hypoxemia triggers the sympathetic process's overactivity, leading to the development of resistant hypertension in OSA. Thus, we hypothesize to evaluate the association between resistant hypertension and OSA.

Methods

The PubMed, ClinicalTrails.gov, CINAHL, Google Scholar, Cochrane Library, and Science Direct databases were searched from 2000 to January 2022 for studies demonstrating the association between resistant hypertension and OSA. The eligible articles underwent quality appraisal, meta-analysis, and heterogeneity assessment.

Results

This study comprises seven studies, including 2,541 patients ranged from 20 to 70 years. The pooled analysis of six studies demonstrated that OSAS patients with a history of increased age, gender, obesity, and smoking status are at an increased risk for resistant hypertension (OR: 4.16 [3.07, 5.64], I2:0%) than the non-OSAS patients. Similarly, the pooled effect demonstrated that patients with OSAS were at an increased risk of resistant hypertension (OR: 3.34 [2.44, 4.58]; I2:0%) than the non-OSAS patients when all associated risk factors were adjusted using multivariate analysis.

Conclusion

This study concludes that OSAS patients with or without related risk factors demonstrated increased risk for resistant hypertension.
Endothelial dysfunction triggers acute respiratory distress syndrome in patients with sepsis: a narrative review
Authors: Cusack Rachael , Bos Lieuwe D. , Povoa Pedro , Martin-Loeches Ignacio
Published: June 2023

Acute respiratory distress syndrome (ARDS) is a severe organ failure occurring mainly in critically ill patients as a result of different types of insults such as sepsis, trauma or aspiration. Sepsis is the main cause of ARDS, and it contributes to a high mortality and resources consumption both in hospital setting and in the community. ARDS develops mainly an acute respiratory failure with severe and often refractory hypoxemia. ARDS also has long term implications and sequelae. Endothelial damage plays an important role in the pathogenesis of ARDS. Understanding the mechanisms of ARDS presents opportunities for novel diagnostic and therapeutic targets. Biochemical signals can be used in concert to identify and classify patients into ARDS phenotypes allowing earlier effective treatment with personalised therapies. This is a narrative review where we aimed to flesh out the pathogenetic mechanisms and heterogeneity of ARDS. We examine the links between endothelium damage and its contribution to organ failure. We have also investigated future strategies for treatment with a special emphasis in endothelial damage.
Evaluation of Low-Cost Phage-Based Microbial Source Tracking Tools for Elucidating Human Fecal Contamination Pathways in Kolkata, India
Authors: Kapoor Renuka , Ebdon James , Wadhwa Ashutosh , Chowdhury Goutam , Wang Yuke , Raj Suraja J. , Siesel Casey , Durry Sarah E. , Mairinger Wolfgang , Mukhopadhyay Asish K. , Kanungo Suman , Dutta Shanta , Moe Christine L.
Published: June 2023

Graphical Abstract

Phages infecting Bacteroides fragilis strain GB-124 and non-source specific somatic coliphages (SOMCPH) were deployed for identification of fecal contamination pathways in Kolkata, India. Analyses of environmental samples representative of nine different exposure pathways, pooled sewage from shared community toilets and sewage from pumping stations showed the presence of both SOMCPH and GB-124 phages in all the sample types.
Differential distribution patterns and assembly processes of soil microbial communities under contrasting vegetation types at distinctive altitudes in the Changbai Mountain
Authors: Kang Yujuan , Wu Haitao , Zhang Yifan , Wu Qiong , Guan Qiang , Lu Kangle , Lin Yiling
Published: June 2023

Diversity patterns and community assembly of soil microorganisms are essential for understanding soil biodiversity and ecosystem processes. Investigating the impacts of environmental factors on microbial community assembly is crucial for comprehending the functions of microbial biodiversity and ecosystem processes. However, these issues remain insufficiently investigated in related studies despite their fundamental significance. The present study aimed to assess the diversity and assembly of soil bacterial and fungal communities to altitude and soil depth variations in mountain ecosystems by using 16S and ITS rRNA gene sequence analyses. In addition, the major roles of environmental factors in determining soil microbial communities and assembly processes were further investigated. The results showed a U-shaped pattern of the soil bacterial diversity at 0–10  cm soil depth along altitudes, reaching a minimum value at 1800 m, while the fungal diversity exhibited a monotonically decreasing trend with increasing altitude. At 10–20  cm soil depth, the soil bacterial diversity showed no apparent changes along altitudinal gradients, while the fungal Chao1 and phylogenetic diversity (PD) indices exhibited hump-shaped patterns with increasing altitude, reaching a maximum value at 1200 m. Soil bacterial and fungal communities were distinctively distributed with altitude at the same depth of soil, and the spatial turnover rates in fungi was greater than in bacteria. Mantel tests suggested soil physiochemical and climate variables significantly correlated with the β diversity of microbial community at two soil depths, suggesting both soil and climate heterogeneity contributed to the variation of bacterial and fungal community. Correspondingly, a novel phylogenetic null model analysis demonstrated that the community assembly of soil bacterial and fungal communities were dominated by deterministic and stochastic processes, respectively. The assembly processes of bacterial community were significantly related to the soil DOC and C:N ratio, while the fungal community assembly processes were significantly related to the soil C:N ratio. Our results provide a new perspective to assess the responses of soil microbial communities to variations with altitude and soil depth.
Screening of bacteriocin-producing dairy Enterococcus strains using low-cost culture media
Authors: Garmasheva Inna L. , Oleschenko Ljubov T.
Published: June 2023

This study was carried out to select the bacteriocinogenic strains among Enterococcus strains isolated from Ukrainian traditional dairy products using a low-cost media for screening, that containing molasses and steep corn liquor. A total of 475 Enterococcus spp. strains were screened for antagonistic activity against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Listeria monocytogenes indicator strains. The initial screening revealed that 34 Enterococcus strains during growth in low-cost medium containing corn steep liquor, peptone, yeast extract, and sucrose produced metabolites with inhibition activity against at least of the indicator strains used. Enterocin genes entA, entP, and entB were detected in 5 Enterococcus strains by PCR assay. Genes of enterocins A and P were found in E. faecalis 58 and Enterococcus sp. 226 strains, enterocins B and P – in Enterococcus sp. 423, enterocin A – in E. faecalis 888 and E. durans 248 strains. Bacteriocin-like inhibitory substances (BLIS) produced by these Enterococcus strains were thermostable and sensitive to proteolytic enzymes. To our knowledge, this is the first report on the isolation of enterocin-producing wild Enterococcus strains from traditional Ukrainian dairy products using a low-cost media for screening bacteriocinogenic strains. Strains E. faecalis 58, Enterococcus sp. 423, and Enterococcus sp. 226 are promising candidates for practical use as producers of bacteriocins with inhibitory activity against L. monocytogenes using molasses and steep corn liquor as cheap sources of carbon and nitrogen, that can significantly reduce the cost of industrial bacteriocin production. Further studies will be required to determine the dynamic of bacteriocin production, its structure, and mechanisms of antibacterial action.
The supragenic organization of glycoside hydrolase encoding genes reveals distinct strategies for carbohydrate utilization in bacteria
Authors: Berlemont Renaud
Published: June 2023

Glycoside hydrolases (GHs) are carbohydrate-active enzymes essential for many environmental (e.g., carbon cycling) and biotechnological (e.g., biofuels) processes. The complete processing of carbohydrates by bacteria requires many enzymes acting synergistically. Here, I investigated the clustered or scattered distribution of 406,337 GH-genes and their association with transporter genes identified in 15,640 completely sequenced bacterial genomes. Different bacterial lineages displayed conserved levels of clustered or scattered GH-genes, but overall, the GH-genes clustering was generally higher than in randomized genomes. In lineages with highly clustered GH-genes (e.g., Bacteroides, Paenibacillus), clustered genes shared the same orientation. These codirectional gene clusters potentially facilitate the genes' co-expression by allowing transcriptional read-through and, at least in some cases, forming operons. In several taxa, the GH-genes clustered with distinct types of transporter genes. The type of transporter genes and the distribution of the so-called GH:TR-genes clusters were conserved in selected lineages. Globally, the phylogenetically conserved clustering of the GH-genes with transporter genes highlights the central function of carbohydrate processing across bacterial lineages. In addition, in bacteria with the most identified GH-genes, the genomic adaptations for carbohydrate processing also mirrored the broad environmental origin of the sequenced strains (e.g., soil and mammal gut) suggesting that a combination of evolutionary history and the environment selects for the specific supragenic organization of the GH-genes supporting the carbohydrate processing in bacterial genomes.
Mechanisms of low susceptibility to the disinfectant benzalkonium chloride in a multidrug-resistant environmental isolate of Aeromonas hydrophila
Authors: Chacón Luz , Kuropka Benno , González-Tortuero Enrique , Schreiber Frank , Rojas-Jiménez Keilor , Rodríguez-Rojas Alexandro
Published: June 2023

Excessive discharge of quaternary ammonium disinfectants such as benzalkonium chloride (BAC) into aquatic systems can trigger several physiological responses in environmental microorganisms. In this study, we isolated a less-susceptible strain of Aeromonas hydrophila to BAC, designated as INISA09, from a wastewater treatment plant in Costa Rica. We characterized its phenotypic response upon exposure to three different concentrations of BAC and characterized mechanisms related to its resistance using genomic and proteomic approaches. The genome of the strain, mapped against 52 different sequenced A. hydrophila strains, consists of approximately 4.6 Mb with 4,273 genes. We found a massive genome rearrangement and thousands of missense mutations compared to the reference strain A. hydrophila ATCC 7966. We identified 15,762 missense mutations mainly associated with transport, antimicrobial resistance, and outer membrane proteins. In addition, a quantitative proteomic analysis revealed a significant upregulation of several efflux pumps and the downregulation of porins when the strain was exposed to three BAC concentrations. Other genes related to membrane fatty acid metabolism and redox metabolic reactions also showed an altered expression. Our findings indicate that the response of A. hydrophila INISA09 to BAC primarily occurs at the envelop level, which is the primary target of BAC. Our study elucidates the mechanisms of antimicrobial susceptibility in aquatic environments against a widely used disinfectant and will help better understand how bacteria can adapt to biocide pollution. To our knowledge, this is the first study addressing the resistance to BAC in an environmental A. hydrophila isolate. We propose that this bacterial species could also serve as a new model to study antimicrobial pollution in aquatic environments.
Epidemiology and zoonotic transmission of mcr-positive and carbapenemase-producing Enterobacterales on German turkey farms
Authors: Nordhoff Katja , Scharlach Martina , Effelsberg Natalie , Knorr Carolin , Rocker Dagmar , Claussen Katja , Egelkamp Richard , Mellmann Alexander C. , Moss Andreas , Müller Ilona , Roth Sarah Andrea , Werckenthin Christiane , Wöhlke Anne , Ehlers Joachim , Köck Robin
Published: June 2023

Introduction

The emergence of carbapenem-resistant bacteria causing serious infections may lead to more frequent use of previously abandoned antibiotics like colistin. However, mobile colistin resistance genes (mcr) can jeopardise its effectiveness in both human and veterinary medicine. In Germany, turkeys have been identified as the food-producing animal most likely to harbour mcr-positive colistin-resistant Enterobacterales (mcr-Col-E). Therefore, the aim of the present study was to assess the prevalence of both mcr-Col-E and carbapenemase-producing Enterobacterales (CPE) in German turkey herds and humans in contact with these herds.

Methods

In 2018 and 2019, 175 environmental (boot swabs of turkey faeces) and 46 human stool samples were analysed using a combination of enrichment-based culture, PCR, core genome multilocus sequence typing (cgMLST) and plasmid typing.

Results

mcr-Col-E were detected in 123 of the 175 turkey farms in this study (70.3%). mcr-Col-E isolates were Escherichia coli (98.4%) and Klebsiella spp. (1.6%). Herds that had been treated with colistin were more likely to harbour mcr-Col-E, with 82.2% compared to 66.2% in untreated herds (p = 0.0298). Prevalence also depended on husbandry, with 7.1% mcr-Col-E in organic farms compared to 74.5% in conventional ones (p < 0.001). In addition, four of the 46 (8.7%) human participants were colonised with mcr-Col-E. mcr-Col-E isolates from stables had minimum inhibitory concentrations (MICs) from 4 to ≥ 32 mg/l, human isolates ranged from 4 to 8 mg/l. cgMLST showed no clonal transmission of isolates. For one farm, plasmid typing revealed great similarities between plasmids from an environmental and a human sample. No CPE were found in turkey herds or humans.

Discussion

These findings confirm that mcr-Col-E-prevalence is high in turkey farms, but no evidence of direct zoonotic transmission of clonal mcr-Col-E strains was found. However, the results indicate that plasmids may be transmitted between E. coli isolates from animals and humans.
Unlocking antagonistic potential of Bacillus amyloliquefaciens KRS005 to control gray mold
Authors: Qi Hong-Yue , Wang Dan , Han Dongfei , Song Jian , Ali Muhammad , Dai Xiao-Feng , Zhang Xiao-Jun , Chen Jie-Yin
Published: June 2023

To establish a safe, efficient, and simple biocontrol measure for gray mold disease caused by Botrytis cinerea, the basic characteristics and antifungal activity of KRS005 were studied from multiple aspects including morphological observation, multilocus sequence analysis and typing (MLSA–MLST), physical-biochemical assays, broad-spectrum inhibitory activities, control efficiency of gray mold, and determination of plant immunity. The strain KRS005, identified as Bacillus amyloliquefaciens, demonstrated broad-spectrum inhibitory activities against various pathogenic fungi by dual confrontation culture assays, of which the inhibition rate of B. cinerea was up to 90.3%. Notably, through the evaluation of control efficiency, it was found that KRS005 fermentation broth could effectively control the occurrence of tobacco leaves gray mold by determining the lesion diameter and biomass of B. cinerea on tobacco leaves still had a high control effect after dilution of 100 folds. Meanwhile, KRS005 fermentation broth had no impact on the mesophyll tissue of tobacco leaves. Further studies showed that plant defense-related genes involved in reactive oxygen species (ROS), salicylic acid (SA), and jasmonic acid (JA)-related signal pathways were significantly upregulated when tobacco leaves were sprayed with KRS005 cell-free supernatant. In addition, KRS005 could inhibit cell membrane damage and increase the permeability of B. cinerea. Overall, KRS005, as a promising biocontrol agent, would likely serve as an alternative to chemical fungicides to control gray mold.
Label-free detection and identification of single bacteria via terahertz near-field imaging
Authors: Wang Jie , Peng Liang , Han Dongxue , Zheng Teng , Chang Tianying , Cui Hong-Liang
Published: June 2023

In recent years, terahertz (THz) imaging has attracted much attention because of its ability to obtain physical and chemical information in a label-free, noninvasive and nonionizing manner. However, the low spatial resolution of traditional THz imaging systems and the weak dielectric response of biological samples hinder the application of this technology in the biomedical field. In this paper, we report a new THz near-field imaging method for a single bacteria, through the coupling effect of nanoscale radius of probe and platinum gold substrate, which greatly enhances THz near-field signal of biological samples. A THz super-resolution image of bacteria has been successfully obtained by strictly controlling the relevant test parameters such as tip parameters and driving amplitude. By analyzing and processing the THz spectral image, the morphology and inner structure of bacteria have been observed. The method has been used to detect and identify Escherichia coli represented by Gram-negative bacteria and Staphylococcus aureus represented by Gram-positive bacteria. This application provides a new label-free, noninvasive and nonionizing testing protocol for the detection of single bacteria.
Quantitative plasma profiling by 1H NMR-based metabolomics: impact of sample treatment
Authors: Madrid-Gambin Francisco , Oller Sergio , Marco Santiago , Pozo Óscar J. , Andres-Lacueva Cristina , Llorach Rafael
Published: June 2023

Introduction: There is evidence that sample treatment of blood-based biosamples may affect integral signals in nuclear magnetic resonance-based metabolomics. The presence of macromolecules in plasma/serum samples makes investigating low-molecular-weight metabolites challenging. It is particularly relevant in the targeted approach, in which absolute concentrations of selected metabolites are often quantified based on the area of integral signals. Since there are a few treatments of plasma/serum samples for quantitative analysis without a universally accepted method, this topic remains of interest for future research.

Methods: In this work, targeted metabolomic profiling of 43 metabolites was performed on pooled plasma to compare four methodologies consisting of Carr-Purcell-Meiboom-Gill (CPMG) editing, ultrafiltration, protein precipitation with methanol, and glycerophospholipid solid-phase extraction (g-SPE) for phospholipid removal; prior to NMR metabolomics analysis. The effect of the sample treatments on the metabolite concentrations was evaluated using a permutation test of multiclass and pairwise Fisher scores.

Results: Results showed that methanol precipitation and ultrafiltration had a higher number of metabolites with coefficient of variation (CV) values above 20%. G-SPE and CPMG editing demonstrated better precision for most of the metabolites analyzed. However, differential quantification performance between procedures were metabolite-dependent. For example, pairwise comparisons showed that methanol precipitation and CPMG editing were suitable for quantifying citrate, while g-SPE showed better results for 2-hydroxybutyrate and tryptophan.

Discussion: There are alterations in the absolute concentration of various metabolites that are dependent on the procedure. Considering these alterations is essential before proceeding with the quantification of treatment-sensitive metabolites in biological samples for improving biomarker discovery and biological interpretations. The study demonstrated that g-SPE and CPMG editing are effective methods for removing proteins and phospholipids from plasma samples for quantitative NMR analysis of metabolites. However, careful consideration should be given to the specific metabolites of interest and their susceptibility to the sample treatment procedures. These findings contribute to the development of optimized sample preparation protocols for metabolomics studies using NMR spectroscopy.
The role of gut microbiota in depression: an analysis of the gut-brain axis
Authors: Irum Natasha , Afzal Tayyeba , Faraz Muhammad Hamid , Aslam Zeeshan , Rasheed Faisal
Published: June 2023

The gut-brain axis is a communication pathway that allows a two-way exchange of information between the microbiota of the gastrointestinal tract and the nervous system of humans. The vagus nerve, which is responsible for facilitating communication, provides support for this axis. The gut-brain axis is currently the subject of research, but studies into the diversity and stratification of the gut microbiota are just getting started. Researchers have discovered several positive trends by analyzing numerous studies examining the gut microbiota’s impact on the effectiveness of SSRIs. It is common knowledge that a specific group of measurable, microbial markers has been recognized as being present in the feces of individuals suffering from depression. Specific bacterial species are a common denominator among therapeutic bacteria used to treat depression. It can also play a role in determining the severity of disease progression. Evidence that selective serotonin reuptake inhibitors (SSRIs) rely on the vagus nerve to exert their therapeutic effects has provided further support for the importance of the vagus nerve in the gut-brain axis, which is necessary for beneficial changes in the gut microbiota. This review will analyze the research linking gut microbiota to depression.
MCR-ALS-based muscle synergy extraction method combined with LSTM neural network for motion intention detection
Authors: Zhao Dazheng , Ma Yehao , Meng Jingyan , Hu Yang , Hong Mengqi , Zhang Jiaji , Zuo Guokun , Lv Xiao , Liu Yunfeng , Shi Changcheng
Published: June 2023

Introduction

The time-varying and individual variability of surface electromyographic signals (sEMG) can lead to poorer motor intention detection results from different subjects and longer temporal intervals between training and testing datasets. The consistency of using muscle synergy between the same tasks may be beneficial to improve the detection accuracy over long time ranges. However, the conventional muscle synergy extraction methods, such as non-negative matrix factorization (NMF) and principal component analysis (PCA) have some limitations in the field of motor intention detection, especially in the continuous estimation of upper limb joint angles.

Methods

In this study, we proposed a reliable multivariate curve-resolved-alternating least squares (MCR-ALS) muscle synergy extraction method combined with long-short term memory neural network (LSTM) to estimate continuous elbow joint motion by using the sEMG datasets from different subjects and different days. The pre-processed sEMG signals were then decomposed into muscle synergies by MCR-ALS, NMF and PCA methods, and the decomposed muscle activation matrices were used as sEMG features. The sEMG features and elbow joint angular signals were input to LSTM to establish a neural network model. Finally, the established neural network models were tested by using sEMG dataset from different subjects and different days, and the detection accuracy was measured by correlation coefficient.

Results

The detection accuracy of elbow joint angle was more than 85% by using the proposed method. This result was significantly higher than the detection accuracies obtained by using NMF and PCA methods. The results showed that the proposed method can improve the accuracy of motor intention detection results from different subjects and different acquisition timepoints.

Discussion

This study successfully improves the robustness of sEMG signals in neural network applications using an innovative muscle synergy extraction method. It contributes to the application of human physiological signals in human-machine interaction.
Toxic encephalopathy and peripheral neuropathy of poisoning by Avermectin Pyridine: a case report and a review of the literature
Authors: Diao Jiuzhou , Zhou Qingbo
Published: June 2023

Background

Avermectin Pyridaben (AVP) is an insecticide with extreme neurotoxicity in human, causing critical symptoms such as nausea, vomiting, coma and respiratory failure within a short time after oral ingestion. Neurological sequelae or even death may occur because of delayed treatment or excessive toxic dose.

Case presentation

We report a 15-year-old girl who presented with coma, respiratory failure, limb weakness, ataxia symptoms after ingestion of a toxic dose of AVP. Soon after the poisoning, the patient was treated with life-saving mechanical ventilation and haemodialysis. Subsequently brain Magnetic Resonance Imaging (MRI) and nerve conduction study (NCS) and electromyography (EMG) demonstrated toxic encephalopathy and peripheral nerve injury. Over the next 2 months the patient’s limb function gradually recovered under treatment with hyperbaric oxygen, glucocorticoid pulses and neurotrophic drugs.

Conclusion

This case documents a rare presentation of toxic encephalopathy complicated with peripheral neuropathy following AVP poisoning. Seven other similar cases of poisoning in terms of common symptoms and effective treatment have also been summarised for providing clinicians with experience in diagnosis and therapy.
Comparison of children with and without dyslexia using functional head impulse test and pediatric balance scale
Authors: Ölçek Gül , Çelik İlayda , Başoǧlu Yuşa , Kaymakçı Sude , Gürlek Emre
Published: June 2023

Purpose

The aim of this study is to compare functionality of vestibulo-ocular reflex (VOR) responses to evaluate the functional properties of the vestibular system and daily balance performance in children with dyslexia and children with normal development.

Method

Fifteen participants diagnosed with dyslexia were included in the study group (SG), and 15 healthy participants were included in the control group (CG). All groups underwent Functional Head Impulse Test (f-HIT) and Pediatric Balance Scale (PBS). f-HIT was performed with at least 15 head impulses at 4000-5000-6000°/s2 randomly to the right and left in the plane of the horizontal semicircular canal (SCC). Statistical analysis was performed using descriptive statistics and the Mann-Whitney U test.

Results

SG percentage values were obtained lower than CG percentage values. Comparisons between the two groups showed that there was a significant difference in all parameters (4000-5000-6000°/s2 and total) in the right-side stimulation, there was significant difference for 4,000 s2 and total correct answers in the left side. In addition, although there was no significant difference between the groups in terms of the PBS score, the SG scores were lower (p = 0.062).

Conclusions

As a novel test, f-HIT, revealed the difference in functionality of vestibular performance in the dyslexia group. In the dyslexia group, f-HIT may be helpful in evaluating and monitoring the vestibular system.
Iranian clinical practice guideline for amyotrophic lateral sclerosis
Authors: Boostani Reza , Olfati Nahid , Shamshiri Hosein , Salimi Zanireh , Fatehi Farzad , Hedjazi Seyed Arya , Fakharian Atefeh , Ghasemi Majid , Okhovat Ali Asghar , Basiri Keivan , Haghi Ashtiani Bahram , Ansari Behnaz , Raissi Gholam Reza , Khatoonabadi Seyed Ahmadreza , Sarraf Payam , Movahed Sara , Panahi Akram , Ziaadini Bentolhoda , Yazdchi Mohammad , Bakhtiyari Jalal , Nafissi Shahriar
Published: June 2023

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegeneration involving motor neurons. The 3–5 years that patients have to live is marked by day-to-day loss of motor and sometimes cognitive abilities. Enormous amounts of healthcare services and resources are necessary to support patients and their caregivers during this relatively short but burdensome journey. Organization and management of these resources need to best meet patients' expectations and health system efficiency mandates. This can only occur in the setting of multidisciplinary ALS clinics which are known as the gold standard of ALS care worldwide. To introduce this standard to the care of Iranian ALS patients, which is an inevitable quality milestone, a national ALS clinical practice guideline is the necessary first step. The National ALS guideline will serve as the knowledge base for the development of local clinical pathways to guide patient journeys in multidisciplinary ALS clinics. To this end, we gathered a team of national neuromuscular experts as well as experts in related specialties necessary for delivering multidisciplinary care to ALS patients to develop the Iranian ALS clinical practice guideline. Clinical questions were prepared in the Patient, Intervention, Comparison, and Outcome (PICO) format to serve as a guide for the literature search. Considering the lack of adequate national/local studies at this time, a consensus-based approach was taken to evaluate the quality of the retrieved evidence and summarize recommendations.