bluuebunny/crossref_metadata_2025 huggingface dataset:
Acquisition of a Stable and Transferable blaNDM-5-Positive Plasmid With Low Fitness Cost Leading to Ceftazidime/Avibactam Resistance in KPC-2-Producing Klebsiella pneumoniae During Treatment
Authors: Huang Jiangqing , Zhang Shengcen , Zhao Zhichang , Chen Min , Cao Yingping , Li Bin
Published: July 2021

The emergence and prevalence of carbapenem-resistant Enterobacteriaceae (CRE) have drawn worldwide attention. Ceftazidime/avibactam (CAZ/AVI) gives us a valuable alternative strategy to treat CRE infections. Unfortunately, CAZ/AVI resistance could occur during CAZ/AVI treatment. The CAZ/AVI-resistant Carbapenem-resistant Klebsiella pneumoniae (CR-KP) (KP137060) and earlier CAZ/AVI-susceptible isolate (KP135194) from the same hospitalized patient were collected at Fujian Medical University Union Hospital between October and November 2019. In this study, CAZ/AVI MICs of CAZ/AVI-susceptible and -resistant isolates (KP135194 and KP137060) were 4 mg/L and 128 mg/L, respectively; and the two isolates had the same antibiotic resistance pattern to other carbapenems. Two strains were then submitted for whole-genome sequencing and bioinformatic analysis. ompK36 was not detected in two isolates. No mutation was observed in blaKPC-2, ompK35 and ompK37 in this study and there was no significant difference of the expression in blaKPC-2, ompK35 and ompK37 between the two isolates (p>0.05). Two isolates were sequence type 11 and harbored blaKPC-2, blaSHV-182 and blaTEM-1B. Compared with KP135194, KP137060 harbored an additional blaNDM-5 positive plasmid. blaNDM-5 gene could be successfully transferred into E. coli J53 at a conjugation frequency of 1.14×10-4. Plasmid stability testing showed that blaKPC-2- and blaNDM-5-harboring plasmids were still stably maintained in the hosts. Growth assay and growth competition experiments showed there was no significant difference in fitness cost between two CR-KP isolates. Our study described the acquisition of a blaNDM-5-harboring plasmid leading to resistance to ceftazidime/avibactam in KPC-2-producing Klebsiella pneumoniae during treatment. This phenomenon deserves further exploration.
Tityus serrulatus (Scorpion): From the Crude Venom to the Construction of Synthetic Peptides and Their Possible Therapeutic Application Against Toxoplasma gondii Infection
Authors: de Assis Diego Rodney Rodrigues , Pimentel Pollyana Maria de Oliveira , dos Reis Pablo Victor Mendes , Rabelo Rayane Aparecida Nonato , Vitor Ricardo Wagner Almeida , Cordeiro Marta do Nascimento , Felicori Liza Figueiredo , Olórtegui Carlos Delfin Chávez , Resende Jarbas Magalhães , Teixeira Mauro Martins , Borges Márcia Helena , de Lima Maria Elena , Pimenta Adriano Monteiro de Castro , Machado Fabiana Simão
Published: July 2021

Toxoplasmosis, caused by Toxoplasma gondii, is a major public concern owing to its neurotropic nature and high morbidity and mortality rates in immunocompromised patients and newborns. Current treatment for this disease is inefficient and produces side effects. Inflammatory mediators produced during T. gondii infection (e.g., cytokines and nitric oxide) are crucial in controlling parasite replication. In this context, Tityus serrulatus venom (TsV) induces the production of inflammatory mediators by immune cells. Thus, this study aimed to isolate and identify the components of TsV with potential anti-T. gondii activity. TsV was extracted from scorpions and lyophilized or loaded onto a column to obtain its fractions. TsV subfractions were obtained using chromatography, and its amino acid sequence was identified and applied to peptide design using bioinformatics tools. The C57BL/6 mice and their harvested macrophages were used to test the anti-Toxoplasma activity of TsV components and peptides. TsV and its fraction F6 attenuated the replication of tachyzoites in macrophages and induced nitric oxide and cytokine (IL-12, TNF, and IL-6) production by infected cells, without host cell toxicity. Moreover, Su6-B toxin, a subfraction of F6, demonstrated anti-T. gondii activity. The partially elucidated and characterized amino acid sequence of Sub6-B demonstrated 93% similarity with T. serrulatus 2 toxin (Ts2). Ts2 mimetic peptides (“Pep1,” “Pep2a,” and “Pep2b”) were designed and synthesized. Pep1 and Pep2a, but not Pep2b, reduced the replication of tachyzoites in macrophages. In vivo, treatment of T. gondii-infected mice with Pep1, Pep2a, or Pep2b decreased the number of cerebral cysts and did not induce hepatotoxicity in the animals. Taken together, our data show promising immunomodulatory and antiparasitic activity of TsV that could be explored and applied in future therapies for treating infectious parasitic diseases such as toxoplasmosis.
L2 Processing of Words Containing English /æ/-/ɛ/ and /l/-/ɹ/ Contrasts, and the Uses and Limits of the Auditory Lexical Decision Task for Understanding the Locus of Difficulty
Authors: Barrios Shannon , Hayes-Harb Rachel
Published: July 2021

Second language (L2) learners often exhibit difficulty perceiving novel phonological contrasts and/or using them to distinguish similar-sounding words. The auditory lexical decision (LD) task has emerged as a promising method to elicit the asymmetries in lexical processing performance that help to identify the locus of learners’ difficulty. However, LD tasks have been implemented and interpreted variably in the literature, complicating their utility in distinguishing between cases where learners’ difficulty lies at the level of perceptual and/or lexical coding. Building on previous work, we elaborate a set of LD ordinal accuracy predictions associated with various logically possible scenarios concerning the locus of learner difficulty, and provide new LD data involving multiple contrasts and native language (L1) groups. The inclusion of a native speaker control group allows us to isolate which patterns are unique to L2 learners, and the combination of multiple contrasts and L1 groups allows us to elicit evidence of various scenarios. We present findings of an experiment where native English, Korean, and Mandarin speakers completed an LD task that probed the robustness of listeners’ phonological representations of the English /æ/-/ɛ/ and /l/-/ɹ/ contrasts. Words contained the target phonemes, and nonwords were created by replacing the target phoneme with its counterpart (e.g.,lecture/*[ɹ]ecture,battle/*b[ɛ]ttle). For the /æ/-/ɛ/ contrast, all three groups exhibited the same pattern of accuracy: near-ceiling acceptance of words and an asymmetric pattern of responses to nonwords, with higher accuracy for nonwords containing [æ] than [ɛ]. For the /l/-/ɹ/ contrast, we found three distinct accuracy patterns: native English speakers’ performance was highly accurate and symmetric for words and nonwords, native Mandarin speakers exhibited asymmetries favoring [l] items for words and nonwords (interpreted as evidence that they experienced difficulty at the perceptual coding level), and native Korean speakers exhibited asymmetries in opposite directions for words (favoring [l]) and nonwords (favoring [ɹ]; evidence of difficulty at the lexical coding level). Our findings suggest that the auditory LD task holds promise for determining the locus of learners’ difficulty with L2 contrasts; however, we raise several issues requiring attention to maximize its utility in investigating L2 phonolexical processing.
Association Between Stress Hyperglycemia Ratio and In-hospital Outcomes in Elderly Patients With Acute Myocardial Infarction
Authors: Chen Guo , Li Mingmin , Wen Xiaodan , Wang Rui , Zhou Yingling , Xue Ling , He Xuyu
Published: July 2021

Backgrounds: Emerging evidence suggests that stress hyperglycemia ratio (SHR), an index of relative stress hyperglycemia, is of great prognostic value in acute myocardial infarction (AMI), but current evidence is limited in elderly patients. In this study, we aimed to assess whether SHR is associated with in-hospital outcomes in elderly patients with AMI.

Methods: In this retrospective study, patients who were aged over 75 years and diagnosed with AMI were consecutively enrolled from 2015, January 1st to 2019, December 31th. Admission blood glucose and glycosylated hemoglobin (HbA1C) during the index hospitalization were used to calculate SHR. Restricted quadratic splines, receiver-operating curves, and logistic regression were performed to evaluate the association between SHR and in-hospital outcomes, including in-hospital all-cause death and in-hospital major adverse cardiac and cerebrovascular events (MACCEs) defined as a composite of all-cause death, cardiogenic shock, reinfarction, mechanical complications of MI, stroke, and major bleeding.

Results: A total of 341 subjects were included in this study. Higher SHR levels were observed in patients who had MACCEs (n = 69) or death (n = 44) during hospitalization. Compared with a SHR value below 1.25, a high SHR was independently associated with in-hospital MACCEs (odds ratio [OR]: 2.945, 95% confidence interval [CI]: 1.626–5.334, P < 0.001) and all-cause death (OR: 2.871 95% CI: 1.428–5.772, P = 0.003) in univariate and multivariate logisitic analysis. This relationship increased with SHR levels based on a non-linear dose-response curve. In contrast, admission glucose was only associated with clinical outcomes in univariate analysis. In subgroup analysis, high SHR was significantly predictive of worse in-hospital clinical outcomes in non-diabetic patients (MACCEs: 2.716 [1.281–5.762], P = 0.009; all-cause death: 2.394 [1.040–5.507], P = 0.040), but the association was not significant in diabetic patients.

Conclusion: SHR might serve as a simple and independent indicator of adverse in-hospital outcomes in elderly patients with AMI, especially in non-diabetic population.
Towards Underwater Macroplastic Monitoring Using Echo Sounding
Authors: Broere Sophie , van Emmerik Tim , González-Fernández Daniel , Luxemburg Willem , de Schipper Matthieu , Cózar Andrés , van de Giesen Nick
Published: July 2021

Plastics originating from land are mainly transported to the oceans by rivers. The total plastic transport from land to seas remains uncertain because of difficulties in measuring and the lack of standard observation techniques. A large focus in observations is on plastics floating on the water surface. However, an increasing number of observations suggest that large quantities of plastics are transported in suspension, below the water surface. Available underwater plastic monitoring methods use nets or fish traps that need to be deployed below the surface and are labor-intensive. In this research, we explore the use of echo sounding as an innovative low-cost method to quantify and identify suspended macroplastics. Experiments under controlled and natural conditions using a low-cost off-the-shelf echo sounding device show that plastic items can be detected and identified up to 7 m below the river surface. Eight different debris items (metal can, cup, bottles, food wrappers, food container) were characterized based on their reflection signature. Reflectance from plastic items diverged significantly from organic material and non-plastic anthropogenic debris. During a multi-day trial field expedition in the Guadalete river, Spain, we found that between 0.8 and 6.3 m depth considerable quantities of plastics are transported. As most plastic monitoring and removal strategies focus on the upper layer below the surface (up to approximately 1.5 m depth), a substantial share of the total plastic transport may be neglected. With this paper we 1) demonstrate that echo sounding is a promising tool for underwater plastic monitoring, and 2) emphasize the importance of an improved understanding of the existing plastic loads below the surface.
The Contribution of Submarine Optical Fiber Telecom Cables to the Monitoring of Earthquakes and Tsunamis in the NE Atlantic
Authors: Matias Luis , Carrilho Fernando , Sá Vasco , Omira Rachid , Niehus Manfred , Corela Carlos , Barros José , Omar Yasser
Published: July 2021

Recent developments in optical fiber cable technology allows the use of existing and future submarine telecommunication cables to provide seismic and sea-level information. In this work we study the impact of three different technologies, 1) SMART, Science Monitoring and Reliable Telecommunications; 2) DAS, Distributed Acoustic Sensing, and; 3) LI, Laser Interferometry, for effective earthquake and tsunami monitoring capabilities on the NE Atlantic. The SW Iberia is the source area of the largest destructive earthquake that struck Europe since the year 1000, the November 1, 1755 event. This earthquake generated also a destructive tsunami affecting the whole basin. This tectonically active area is crossed by the CAM (Continent-Azores-Madeira) submarine cable on a ring configuration. Due to the end of cable lifetime the current cables need to be replaced by 2024 and the technical requirements must be defined in mid-2021. The Azores archipelago is the focus of frequent seismic crizes and occasionally destructive earthquakes. A common feature of these seismic events is that they take place offshore, an area that is difficult to monitor from land-based instruments. In this work we evaluate the contribution of SMART cables to the earthquake monitoring and tsunami early warning system in SW Iberia and show how DAS and LI can improve earthquake monitoring on two active domains of the Azores. For tsunami early warning, we show how the offshore sea-level measurements provide clean offshore tsunami records when compared to coastal observations by tide gauges, which greatly improves the efficiency of the system. For earthquake monitoring, the data processing operational routine is examined using Monte-Carlo simulations. These take into consideration the errors in phase picking and the uncertainty on the 1D velocity model used for earthquake location. Quality of earthquake location is examined using the difference between the true location and the centroid of the computed epicenters and by the overall ellipse of uncertainty obtained from 100 runs. The added value provided by instrumented submarine telecommunication cables to mitigate earthquake and tsunami risk demonstrated in this work will help authorities and the society in general to take the political decisions required for its full implementation worldwide.
The Adipose Tissue at the Crosstalk Between EDCs and Cancer Development
Authors: Bokobza Emma , Hinault Charlotte , Tiroille Victor , Clavel Stéphan , Bost Frédéric , Chevalier Nicolas
Published: July 2021

Obesity is a major public health concern at the origin of many pathologies, including cancers. Among them, the incidence of gastro-intestinal tract cancers is significantly increased, as well as the one of hormone-dependent cancers. The metabolic changes caused by overweight mainly with the development of adipose tissue (AT), insulin resistance and chronic inflammation induce hormonal and/or growth factor imbalances, which impact cell proliferation and differentiation. AT is now considered as the main internal source of endocrine disrupting chemicals (EDCs) representing a low level systemic chronic exposure. Some EDCs are non-metabolizable and can accumulate in AT for a long time. We are chronically exposed to low doses of EDCs able to interfere with the endocrine metabolism of the body. Importantly, several EDCs have been involved in the genesis of obesity affecting profoundly the physiology of AT. In parallel, EDCs have been implicated in the development of cancers, in particular hormone-dependent cancers (prostate, testis, breast, endometrium, thyroid). While it is now well established that AT secretes adipocytokines that promote tumor progression, it is less clear whether they can initiate cancer. Therefore, it is important to better understand the effects of EDCs, and to investigate the buffering effect of AT in the context of progression but also initiation of cancer cells using adequate models recommended to uncover and validate these mechanisms for humans. We will review and argument here the potential role of AT as a crosstalk between EDCs and hormone-dependent cancer development, and how to assess it.
Using the Biological Condition Gradient Model as a Bioassessment Framework to Support Rehabilitation and Restoration of the Upper Tana River Watershed in Kenya
Authors: Ndiritu George G. , Terer Taita , Njoroge Peter , Muiruri Veronica M. , Njagi Edward L. , Kosgei Gilbert , Njoroge Laban , Kamau Peris W. , Malonza Patrick K. , Muchane Mary , Gathua Joseph , Odeny Dickens , Courtemanch David
Published: July 2021

The biological condition gradient (BCG), a scientific framework that describes the change in ecosystem characteristics in response to human-induced levels of stressors, was modified and used to characterize watershed habitats in the Upper Tana River watershed, Kenya. The inbuilt utilities of BCG, including its simplicity, versatility, and its robust nature, allowed its use by seven taxonomic groups of macroinvertebrates, diatoms, fish, herpetofauna (amphibians and reptiles), plants, macrofungi, and birds to assess and monitor landscape conditions in both terrestrial and aquatic habitats. The biological data were described using taxa abundance distribution measures followed by multivariate analyses to determine their relationship with water or soil quality and thereafter assessment of taxa tolerant levels in response to environmental stress and disturbances. Preliminary findings reported that the taxonomic groups complemented each other, with each taxonomic group reliably assessing ecological conditions to a certain degree that supported assigning all 36 sampled sites into BCG tiers. The BCG models developed for all taxonomic groups assisted in the identification and selection of taxa indicating varying levels of landscape conditions. These taxa, referred to as flagship or indicator taxa, assist in simplifying the BCG model and, hence, are possible for use by parataxonomists or ordinary citizens to assess and monitor the ecological health of habitats under consideration. Furthermore, the capability of BCG models to assess landscape conditions shows how they can be used to identify important habitats for conservation, direct investment for restoration, and track progress.
Long-Term Evolution of Greenhouse Gas Emissions From Global Reservoirs
Authors: Yan Xingcheng , Thieu Vincent , Garnier Josette
Published: July 2021

The contribution of artificial reservoirs to greenhouse gas (GHG) emissions has been emphasized in previous studies. In the present study, we collected and updated data on GHG emission rates from reservoirs at the global scale, and applied a new classification method based on the hydrobelt concept. Our results showed that CH4 and CO2 emissions were significantly different in the hydrobelt groups (p < 0.01), while no significant difference was found for N2O emissions, possibly due to their limited measurements. We found that annual GHG emissions (calculated as C or N) from global reservoirs amounted to 12.9 Tg CH4-C, 50.8 Tg CO2-C, and 0.04 Tg N2O-N. Furthermore, GHG emissions (calculated as CO2 equivalents) were also estimated for the 1950–2017 period based on the cumulative number and surface area of global reservoirs in the different hydrobelts. The highest increase rate in both the number of reservoirs and their surface area, which occurred from 1950 to the 1980s, led to an increase in GHG emissions from reservoirs. Since then, the increase rate of reservoir construction, and hence GHG emissions, has slowed down. Moreover, we also examined the potential impact of reservoir eutrophication on GHG emissions and found that GHG emissions from reservoirs could increase by 40% under conditions in which total phosphorus would double. In addition, we showed that the characteristics of reservoirs (e.g., geographical location) and their catchments (e.g., surrounding terrestrial net primary production, and precipitation) may influence GHG emissions. Overall, a major finding of our study was to provide an estimate of the impact of large reservoirs during the 1950–2017 period, in terms of GHG emissions. This should help anticipate future GHG emissions from reservoirs considering all reservoirs being planned worldwide. Besides using the classification per hydrobelt and thus reconnecting reservoirs to their watersheds, our study further emphasized the efforts to be made regarding the measurement of GHG emissions in some hydrobelts and in considering the growing number of reservoirs.
Quest for New Space for Restricted Range Mammals: The Case of the Endangered Walia Ibex
Authors: Gebremedhin Berihun , Chala Desalegn , Flagstad Øystein , Bekele Afework , Bakkestuen Vegar , van Moorter Bram , Ficetola G. Francesco , Zimmermann Niklaus E. , Brochmann Christian , Stenseth Nils Chr.
Published: July 2021

Populations of large mammals have declined at alarming rates, especially in areas with intensified land use where species can only persist in small habitat fragments. To support conservation planning, we developed habitat suitability models for the Walia ibex (Capra walie), an endangered wild goat endemic to the Simen Mountains, Ethiopia. We calibrated several models that differ in statistical properties to estimate the spatial extent of suitable habitats of the Walia ibex in the Simen Mountains, as well as in other parts of the Ethiopian highlands to assess potentially suitable areas outside the current distribution range of the species. We further addressed the potential consequences of future climate change using a climate model with four emission scenarios. Model projections estimated the potential suitable habitat under current climate to 501–672 km2in Simen and 6,251–7,732 km2in other Ethiopian mountains. Under projected climate change by 2,080, the suitable habitat became larger in Simen but smaller in other parts of Ethiopia. The projected expansion in Simen is contrary to the general expectation of shrinking suitable habitats for high-elevation species under climate warming and may partly be due to the ruggedness of these particular mountains. The Walia ibex has a wide altitudinal range and is able to exploit very steep slopes, allowing it to track the expected vegetation shift to higher altitudes. However, this potential positive impact may not last long under continued climate warming, as the species will not have much more new space left to colonize. Our study indicates that the current distribution range can be substantially increased by reintroducing and/or translocating the species to other areas with suitable habitat. Indeed, to increase the viability and prospects for survival of this flagship species, we strongly recommend human-assisted reintroduction to other Ethiopian mountains. Emulating the successful reintroduction of the Alpine ibex that has spread from a single mountain in Italy to its historical ranges of the Alps in Europe might contribute to saving the Walia ibex from extinction.
Prediction of BRCA Gene Mutation in Breast Cancer Based on Deep Learning and Histopathology Images
Authors: Wang Xiaoxiao , Zou Chong , Zhang Yi , Li Xiuqing , Wang Chenxi , Ke Fei , Chen Jie , Wang Wei , Wang Dian , Xu Xinyu , Xie Ling , Zhang Yifen
Published: July 2021

Background

Breast cancer is one of the most common cancers and the leading cause of death from cancer among women worldwide. The genetic predisposition to breast cancer may be associated with a mutation in particular genes such as gene BRCA1/2. Patients who carry a germline pathogenic mutation in BRCA1/2 genes have a significantly increased risk of developing breast cancer and might benefit from targeted therapy. However, genetic testing is time consuming and costly. This study aims to predict the risk of gBRCA mutation by using the whole-slide pathology features of breast cancer H&E stains and the patients’ gBRCA mutation status.

Methods

In this study, we trained a deep convolutional neural network (CNN) of ResNet on whole-slide images (WSIs) to predict the gBRCA mutation in breast cancer. Since the dimensions are too large for slide-based training, we divided WSI into smaller tiles with the original resolution. The tile-based classification was then combined by adding the positive classification result to generate the combined slide-based accuracy. Models were trained based on the annotated tumor location and gBRCA mutation status labeled by a designated breast cancer pathologist. Four models were trained on tiles cropped at 5×, 10×, 20×, and 40× magnification, assuming that low magnification and high magnification may provide different levels of information for classification.

Results

A trained model was validated through an external dataset that contains 17 mutants and 47 wilds. In the external validation dataset, AUCs (95% CI) of DL models that used 40×, 20×, 10×, and 5× magnification tiles among all cases were 0.766 (0.763–0.769), 0.763 (0.758–0.769), 0.750 (0.738–0.761), and 0.551 (0.526–0.575), respectively, while the corresponding magnification slides among all cases were 0.774 (0.642–0.905), 0.804 (0.676–0.931), 0.828 (0.691–0.966), and 0.635 (0.471–0.798), respectively. The study also identified the influence of histological grade to the accuracy of the prediction.

Conclusion

In this paper, the combination of pathology and molecular omics was used to establish the gBRCA mutation risk prediction model, revealing the correlation between the whole-slide histopathological images and gRCA mutation risk. The results indicated that the prediction accuracy is likely to improve as the training data expand. The findings demonstrated that deep CNNs could be used to assist pathologists in the detection of gene mutation in breast cancer.
Potential of Mitochondrial Genome Editing for Human Fertility Health
Authors: Fu Lin , Luo Yu-Xin , Liu Ying , Liu Hui , Li Hong-zhen , Yu Yang
Published: July 2021

Mitochondrial DNA (mtDNA) encodes vital proteins and RNAs for the normal functioning of the mitochondria. Mutations in mtDNA leading to mitochondrial dysfunction are relevant to a large spectrum of diseases, including fertility disorders. Since mtDNA undergoes rather complex processes during gametogenesis and fertilization, clarification of the changes and functions of mtDNA and its essential impact on gamete quality and fertility during this process is of great significance. Thanks to the emergence and rapid development of gene editing technology, breakthroughs have been made in mitochondrial genome editing (MGE), offering great potential for the treatment of mtDNA-related diseases. In this review, we summarize the features of mitochondria and their unique genome, emphasizing their inheritance patterns; illustrate the role of mtDNA in gametogenesis and fertilization; and discuss potential therapies based on MGE as well as the outlook in this field.
Effects of Morbid Obesity and Metabolic Syndrome on the Composition of Circulating Immune Subsets
Authors: Wijngaarden Leontine H. , van der Harst Erwin , Klaassen René A. , Dunkelgrun Martin , Kuijper T Martijn , Klepper Mariska , Ambagtsheer Gisela , IJzermans Jan N. M. , de Bruin Ron W. F. , Litjens Nicolle H. R.
Published: July 2021

Morbid obesity is characterized by chronic, low-grade inflammation, which is associated with ‘inflamm-aging’. The presence of metabolic syndrome (MetS) might accelerate this phenomenon of metaflammation. In this study, we assessed the effects of morbid obesity and MetS on the composition of a broad spectrum of immune cells present within the circulation. A total of 117 morbidly obese patients (MOP) without MetS (MetS-), 127 MOP with MetS (MetS+) and 55 lean controls (LC) were included in this study. Absolute numbers of T cell, B cell, NK cell and monocyte subsets were assessed within peripheral blood using flow cytometry. Both absolute cell numbers and proportion of cells were evaluated correcting for covariates age, body mass index and cytomegalovirus serostatus. Although the absolute number of circulating CD4+ T cells was increased in the MetS+ group, the CD4+ T cell composition was not influenced by MetS. The CD8+ T cell and B cell compartment contained more differentiated cells in the MOP, but was not affected by MetS. Even though the absolute numbers of NK cells and monocytes were increased in the MOP as compared to LC, there was no difference in proportions of NK and monocyte subsets between the three study groups. In conclusion, although absolute numbers of CD4+ and CD8+ T cells, B cells, NK cells and monocytes are increased in MOP, obesity-induced effects of the composition of the immune system are confined to a more differentiated phenotype of CD8+ T cells and B cells. These results were not affected by MetS.
Diazepam Impairs Innate and Adaptive Immune Responses and Ameliorates Experimental Autoimmune Encephalomyelitis
Authors: Falcón Cristian R. , Hurst Nicolás Fernández , Vivinetto Ana Laura , López Pablo Héctor Horacio , Zurita Adolfo , Gatti Gerardo , Cervi Laura , Monferran Clara G. , Roth German A.
Published: July 2021

Currently there is increasing attention on the modulatory effects of benzodiazepines on the immune system. Here, we evaluate how Diazepam (DZ) affects both innate and adaptive immunity. We observed that treatment with DZ and Lipopolysaccharide (LPS) on macrophages or dendritic cells (DCs) induced a defective secretion of IL-12, TNF-α, IL-6 and a lesser expression of classical activation markers as NO production and CD40 in comparison with LPS condition. More importantly, mice pre-treated with DZ and then challenged to LPS induced-septic shock showed reduced death. The DZ treatment shifted the LPS-induced pro-inflammatory cytokine production of peritoneal cells (PCs) to an anti-inflammatory profile commanded by IL-10. In agreement with this, DZ treatment prevented LPS-induced DC ability to initiate allogeneic Th1 and Th17 responses in vitro when compared with LPS-matured DC. Since these inflammatory responses are the key in the development of the experimental autoimmune encephalomyelitis (EAE), we treated EAE mice preventively with DZ. Mice that received DZ showed amelioration of clinical signs and immunological parameters of the disease. Additionally, DZ reduced the release of IFN-γ and IL-17 by splenocytes from untreated sick mice in vitro. For this reason, we decided to treat diseased mice therapeutically with DZ when they reached the clinical score of 1. Most importantly, this treatment ameliorated clinical signs, reduced the MOG-specific inflammatory cytokine production and prevented axonal damage. Altogether, these results indicate that DZ is a potent immunomodulator capable of controlling undesired innate and adaptive immune responses, both at the beginning of these responses and also once they have started.
Insight Into Polysaccharides From Panax ginseng C. A. Meyer in Improving Intestinal Inflammation: Modulating Intestinal Microbiota and Autophagy
Authors: Wang Dandan , Shao Shuai , Zhang Yanqiu , Zhao Daqing , Wang Mingxing
Published: July 2021

Polysaccharides from Panax ginseng C. A. Meyer (P. ginseng) are the main active component of P. ginseng and exhibit significant intestinal anti-inflammatory activity. However, the therapeutic mechanism of the ginseng polysaccharide is unclear, and this hinders the application for medicine or functional food. In this study, a polysaccharide was isolated from P. ginseng (GP). The primary structure and morphology of the GP were studied by HPLC, FT-IR spectroscopy, and scanning electron microscopy (SEM). Further, its intestinal anti-inflammatory activity and its mechanism of function were evaluated in experimental systems using DSS-induced rats, fecal microbiota transplantation (FMT), and LPS-stimulated HT-29 cells. Results showed that GP modulated the structure of gut microbiota and restored mTOR-dependent autophagic dysfunction. Consequently, active autophagy suppressed inflammation through the inhibition of NF-κB, oxidative stress, and the release of cytokines. Therefore, our research provides a rationale for future investigations into the relationship between microbiota and autophagy and revealed the therapeutic potential of GP for inflammatory bowel disease.
Employing Broadly Neutralizing Antibodies as a Human Immunodeficiency Virus Prophylactic & Therapeutic Application
Authors: Ding Chengchao , Patel Darshit , Ma Yunjing , Mann Jamie F. S. , Wu Jianjun , Gao Yong
Published: July 2021

Despite the discovery that the human immunodeficiency virus 1 (HIV-1) is the pathogen of acquired immunodeficiency syndrome (AIDS) in 1983, there is still no effective anti-HIV-1 vaccine. The major obstacle to the development of HIV-1 vaccine is the extreme diversity of viral genome sequences. Nonetheless, a number of broadly neutralizing antibodies (bNAbs) against HIV-1 have been made and identified in this area. Novel strategies based on using these bNAbs as an efficacious preventive and/or therapeutic intervention have been applied in clinical. In this review, we summarize the recent development of bNAbs and its application in HIV-1 acquisition prevention as well as discuss the innovative approaches being used to try to convey protection within individuals at risk and being treated for HIV-1 infection.
Viability Status-Dependent Effect of Bifidobacterium longum ssp. longum CCM 7952 on Prevention of Allergic Inflammation in Mouse Model
Authors: Pyclik Marcelina Joanna , Srutkova Dagmar , Razim Agnieszka , Hermanova Petra , Svabova Tereza , Pacyga Katarzyna , Schwarzer Martin , Górska Sabina
Published: July 2021

The classical definition of probiotics states that bacteria must be alive to be beneficial for human organism. However, recent reports show that inactivated bacteria or their effector molecules can also possess such properties. In this study, we investigated the physical and immunomodulatory properties of four Bifidobacterium strains in the heat-treated (HT) and untreated (UN) forms. We showed that temperature treatment of bacteria changes their size and charge, which affects their interaction with epithelial and immune cells. Based on the in vitro assays, we observed that all tested strains reduced the level of OVA-induced IL-4, IL-5, and IL-13 in the spleen culture of OVA-sensitized mice. We selected Bifidobacterium longum ssp. longum CCM 7952 (Bl 7952) for further analysis. In vivo experiments confirmed that untreated Bl 7952 exhibited allergy-reducing properties when administered intranasally to OVA-sensitized mice, which manifested in significant suppression of airway inflammation. Untreated Bl 7952 decreased local and systemic levels of Th2 related cytokines, OVA-specific IgE antibodies and simultaneously inhibited airway eosinophilia. In contrast, heat-treated Bl 7952 was only able to reduce IL-4 levels in the lungs and eosinophils in bronchoalveolar lavage, but increased neutrophil and macrophage numbers. We demonstrated that the viability status of Bl 7952 is a prerequisite for the beneficial effects of bacteria, and that heat treatment reduces but does not completely abolish these properties. Further research on bacterial effector molecules to elucidate the beneficial effects of probiotics in the prevention of allergic diseases is warranted.
M1 Macrophage-Derived Nanovesicles Repolarize M2 Macrophages for Inhibiting the Development of Endometriosis
Authors: Li Qiuju , Yuan Ming , Jiao Xue , Huang Yufei , Li Jing , Li Dong , Ji Miaomiao , Wang Guoyun
Published: July 2021

Background

Endometriosis is a common nonmalignant gynecological disorder that affects 10–15% women of reproductive age and causes several symptoms that result in decreased quality of life and a huge social burden. In recent decades, extracellular vesicles (EVs) have gained attention as a potential therapeutic tool; however, the therapeutic effects of EVs against endometriosis have not been reported. Accordingly, in this study, we investigated the feasibility of nanovesicles (NVs) derived from M1 macrophages (M1NVs) in treating endometriosis.

Methods

M1NVs were prepared by serial extrusion. Co-culture assays were performed to investigate changes in tube formation and migration/invasion of eutopic endometrial stroma cells (ESCs) obtained from patients with endometriosis (EM-ESCs). A mouse model of endometriosis was established, and mice were treated with phosphate-buffered saline, M0NVs, or M1NVs to evaluate the efficacy and safety of M1NV for treating endometriosis.

Results

M1NVs directly or indirectly inhibited the migration and invasion of EM-ESCs and reduced tube formation. In the mouse model, M1NVs suppressed the development of endometriosis through reprogramming of M2 macrophages, without causing damage to the organs.

Conclusions

M1NVs inhibit the development of endometriosis directly, or through repolarizing macrophages from M2 to M1 phenotype. Hence, administration of M1NVs may represent a novel method for the treatment of endometriosis.
Climate and Land Cover Trends Affecting Freshwater Inputs to a Fjord in Northwestern Patagonia
Authors: León-Muñoz Jorge , Aguayo Rodrigo , Marcé Rafael , Catalán Núria , Woelfl Stefan , Nimptsch Jorge , Arismendi Ivan , Contreras Camila , Soto Doris , Miranda Alejandro
Published: July 2021

Freshwater inputs strongly influence oceanographic conditions in coastal systems of northwestern Patagonia (41–45°S). Nevertheless, the influence of freshwater on these systems has weakened in recent decades due to a marked decrease in precipitation. Here we evaluate potential influences of climate and land cover trends on the Puelo River (640 m3s–1), the main source of freshwater input of the Reloncaví Fjord (41.5°S). Water quality was analyzed along the Puelo River basin (six sampling points) and at the discharge site in the Reloncaví Fjord (1, 8, and 25 m depth), through six field campaigns carried out under contrasting streamflow scenarios. We also used several indicators of hydrological alteration, and cross-wavelet transform and coherence analyses to evaluate the association between the Puelo River streamflow and precipitation (1950–2019). Lastly, using the WEAP hydrological model, land cover maps (2001–2016) and burned area reconstructions (1985–2019), we simulated future land cover impacts (2030) on the hydrological processes of the Puelo River. Total Nitrogen and total phosphorus, dissolved carbon, and dissolved iron concentrations measured in the river were 3–15 times lower than those in the fjord. Multivariate analyses showed that streamflow drives the carbon composition in the river. High streamflow conditions contribute with humic and colored materials, while low streamflow conditions corresponded to higher arrival of protein-like materials from the basin. The Puelo River streamflow showed significant trends in magnitude (lower streamflow in summer and autumn), duration (minimum annual streamflow), timing (more floods in spring), and frequency (fewer prolonged floods). The land cover change (LCC) analysis indicated that more than 90% of the basin area maintained its land cover, and that the main changes were attributed to recent large wildfires. Considering these land cover trends, the hydrological simulations project a slight increase in the Puelo River streamflow mainly due to a decrease in evapotranspiration. According to previous simulations, these projections present a direction opposite to the trends forced by climate change. The combined effect of reduction in freshwater input to fiords and potential decline in water quality highlights the need for more robust data and robust analysis of the influence of climate and LCC on this river-fjord complex of northwestern Patagonia.
Molecular Mechanisms of Coral Persistence Within Highly Urbanized Locations in the Port of Miami, Florida
Authors: Rubin Ewelina T. , Enochs Ian C. , Foord Colin , Mayfield Anderson B. , Kolodziej Graham , Basden Isabelle , Manzello Derek P.
Published: July 2021

Healthy coral communities can be found on artificial structures (concrete walls and riprap) within the Port of Miami (PoM), Florida. These communities feature an unusually high abundance of brain corals, which have almost entirely vanished from nearby offshore reefs. These corals appear to be thriving in very low-quality waters influenced by dense ship and boat traffic, dredging, and numerous residential and industrial developments. The PoM basin is part of Biscayne Bay, an estuarine environment that experiences frequent freshwater input, high nutrient loading, hypoxia, and acidification. To investigate if there is a molecular basis behind the ability of these corals to persist within these highly “urbanized” waters, we compared whole transcriptome expression profiles from 25 PoM Pseudodiploria strigosa colonies against six conspecifics from a nearby offshore reef. We found that the urban corals exhibited higher expression of (1) transcripts encoding pattern-recognition receptors which may allow these corals to better sense and detect food particles and pathogenic invaders; (2) digestive and degradation-associated enzymes, which may suggest an elevated capacity for heterotrophy and pathogen digestion; and (3) transcripts related to innate immunity, defense, and cellular detoxification, which may collectively protect against pathogenic organisms and water pollution impacts. Large ribosomal subunit rRNA gene mapping revealed that P. strigosa colonies from the PoM sites predominantly hosted heat-tolerant endosymbionts from the genus Durusdinium while offshore conspecifics’ communities were dominated by symbionts in the genus Breviolum. These findings reveal transcriptomic plasticity and molecular mechanisms contributing to the persistence of these corals within a highly urbanized habitat.
Admission Systolic Blood Pressure and In-hospital Mortality in Acute Type A Aortic Dissection: A Retrospective Observational Study
Authors: Yang Guifang , Peng Wen , Zhou Yang , He Huaping , Pan Xiaogao , Li Xizhao , Chai Xiangping
Published: July 2021

Background: Evidence between admission systolic blood pressure (SBP) and in-hospital deaths in acute type A aortic dissection (AAD) patients is inadequate. Here, we examined the relationship between SBP and in-hospital deaths in AAD patients.

Methods: 703 AAD patients were enrolled from January 2014 to December 2018. The independent and dependent variables targeted were admission SBP and in-hospital deaths, respectively. Gender, age, body mass index (BMI), chronic renal insufficiency, smoking, hypertension, diabetes, laboratory indicators, and management were used as covariates.

Results: The 703 participants had a mean age of 50.48 ± 11.35. About 76.24% of the participants were male. After adjusting for confounders, there was a negative correlation between AAD patients' admission SBP and in-hospital deaths (OR = 0.88, 95%CI 0.80–0.96). Consequently, a non-linear relationship of point 120 (mmHg) was detected between admission SBP and in-hospital deaths for AAD patients. Confidence intervals and effect sizes of the right (SBP >120 mmHg) and left (SBP ≤ 120 mmHg) sides of the inflection point were 0.96 (0.85–1.09) and 0.67 (0.51–0.88), respectively. The change in the male population and non-diabetes people was more pronounced according to subgroup analysis.

Conclusions: Correlation between admission SBP and in-hospital mortality of AAD patients is non-linear. SBP negatively correlated with in-hospital mortality when ≤120 mmHg.
Investigating Research Hotspots and Publication Trends of Spinal Stenosis: A Bibliometric Analysis During 2000–2018
Authors: Yang Keda , Pei Lei , Wen Kaicheng , Zhou Siming , Tao Lin
Published: July 2021

Spinal stenosis is a common disease affecting the elderly that is present in a various forms. Its high incidence forces researchers to pay more attention and offer countermeasures. We used the Web of Science Core collection and PubMed database to obtain 5,606 scientific studies concerning spinal stenosis, and the number of publications maintained a roughly increasing trend from 108 in 2000 to 512 in 2018, only declining in 2011. Bibliometric analysis was conducted using the online analysis software CiteSpace and Bibliographic Item Co-Occurrence Matrix Builder (BICOMB). The United States maintains academic leadership in this field. The journal SPINE was the most authoritative, with 695 articles and an average of 12.73 citations. The exported major MeSH terms were further biclustered with gCLUTO according to co-word analysis to reveal research hotspots, including etiology, pathogenesis, clinical manifestation, conservative treatment, operative indication, internal implantation, and postoperative complications. After combination, the main topics focused on pathogenesis and surgical treatment. Narrowing causes flavum ligamentum hypertrophy, and posterior longitudinal ligament ossification is widely accepted. Additionally, minimally invasive surgery and internal implantation fixation are more valid in the clinic. Refining pathological classification and optimizing surgical methods and instrument properties will be important future research directions for spinal stenosis.
Evaluation of Positive End-Expiratory Pressure Strategies in Patients With Coronavirus Disease 2019–Induced Acute Respiratory Distress Syndrome
Authors: Pan Chun , Lu Cong , She Xiaobin , Ren Haibo , Wei Huazhang , Xu Liang , Huang Yingzi , Xia Jia'an , Yu Yuetian , Chen Lu , Du Bin , Qiu Haibo
Published: July 2021

Background: Different positive end-expiratory pressure (PEEP) strategies are available for subjects with coronavirus disease 2019 (COVID-19)–induced acute respiratory distress syndrome (ARDS) requiring invasive mechanical ventilation. We aimed to evaluate three conventional PEEP strategies on their effects on respiratory mechanics, gas exchanges, and hemodynamics.

Methods: This is a prospective, physiologic, multicenter study conducted in China. We recruited 20 intubated subjects with ARDS and confirmed COVID-19. We first set PEEP by the ARDSnet low PEEP–fraction of inspired oxygen (FIO2) table. After a recruitment maneuver, PEEP was set at 15, 10, and 5 cm H2O for 10 min, respectively. Among these three PEEP levels, best-compliance PEEP was the one providing the highest respiratory system compliance; best-oxygenation PEEP was the one providing the highest PaO2 (partial pressure of arterial oxygen)/FIO2.

Results: At each PEEP level, we assessed respiratory mechanics, arterial blood gas, and hemodynamics. Among three PEEP levels, plateau pressure, driving pressure, mechanical power, and blood pressure improved with lower PEEP. The ARDSnet low PEEP–FIO2 table and the best-oxygenation strategies provided higher PEEP than the best-compliance strategy (11 ± 6 cm H2O vs. 11 ± 3 cm H2O vs. 6 ± 2 cm H2O, p = 0.001), leading to higher plateau pressure, driving pressure, and mechanical power. The three PEEP strategies were not significantly different in gas exchange. The subgroup analysis showed that three PEEP strategies generated different effects in subjects with moderate or severe ARDS (n = 12) but not in subjects with mild ARDS (n = 8).

Conclusions: In our cohort with COVID-19–induced ARDS, the ARDSnet low PEEP/FIO2 table and the best-oxygenation strategies led to higher PEEP and potentially higher risk of ventilator-induced lung injury than the best-compliance strategy.

Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT04359251.