bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatiotemporal Evolution and Improvement Potential of Agricultural Eco-efficiency in Jiangsu Province
Authors: Li Zaijun , Sarwar Suleman , Jin Tao
Published: August 2021

This study evaluated the agricultural eco-efficiency (AEE) of 77 counties and districts in Jiangsu Province from 1999 to 2018 using the slack-based measure (SBM) of efficiency in data envelopment analysis (DEA) (SBM-DEA) and analyzed its spatiotemporal evolution characteristics and influencing factors. We found that 1) the overall AEE, pure technology efficiency (PTE), and scale efficiency (SE) exhibited a fluctuating downward trend. AEE exhibited a significantly positive spatial association and an increasingly widening regional inequality. 2) AEE featured the “high south” and “low north” spatial pattern, with the high-value regions concentrated around the Taihu Lake plain region in southern Jiangsu Province (Sunan) and low-value regions scattered across most of the northern Jiangsu Province (Subei) cities. The high-high and low-low spatial association types further confirmed the existence of the north–south agglomeration pattern. 3) PTE and SE exhibited a similar “high south” and “low north” spatial pattern to that of AEE. The areas with the growth trends of AEE, PTE, and SE were clustered in Xuzhou and Nanjing city and in the bordering regions between Yangzhou and the Huai’an city, and also between Changzhou and the Wuxi city. 4) Excessive redundant input and use of pesticides, chemical fertilizers, agricultural diesel, labor, land, and agricultural carbon emissions, all have been the primary factors affecting Jiangsu’s AEE. Irrigation also considerably affected AEE, while mechanical power and agricultural film have minimal effects. The majority of counties and districts in the Subei, central Jiangsu Province (Suzhong), and Ningzhen Yang Hilly region experienced excessive usage of chemical fertilizers, pesticides, chemical fertilizers, agricultural diesel, labor, and land. The findings can improve understanding of the spatial association effect and underlying impediment of AEE and can further help policymakers promoting agricultural eco-efficiency.
Case Report: CNNM2 Mutations Cause Damaged Brain Development and Intractable Epilepsy in a Patient Without Hypomagnesemia
Authors: Li Xiucui , Bao Shijia , Wang Wei , Shi Xulai , Hu Ying , Li Feng , Zhao Qianlei , Zheng Feixia , Lin Zhongdong
Published: August 2021

A series of neurological manifestations such as intellectual disability and epilepsy are closely related to hypomagnesemia. Cyclin M2 (CNNM2) proteins, as a member of magnesium (Mg2+) transporters, were found along the basolateral membrane of distal renal tubules and involved in the reabsorption of Mg2+. Homozygous and heterozygous variants in CNNM2 reported so far were responsible for a variable degree of hypomagnesemia, several of which also showed varying degrees of neurological phenotypes such as intellectual disability and epilepsy. Here, we report a de novo heterozygous CNNM2 variant (c.2228C > T, p.Ser743Phe) in a Chinese patient, which is the variant located in the cyclic nucleotide monophosphate-binding homology (CNBH) domain of CNNM2 proteins. The patient presented with mild intellectual disability and refractory epilepsy but without hypomagnesemia. Thus, we reviewed the literature and analyzed the phenotypes related to CNNM2 variants, and then concluded that the number of variant alleles and the changed protein domains correlates with the severity of the disease, and speculated that the CNBH domain of CNNM2 possibly plays a limited role in Mg2+ transport but a significant role in brain development. Furthermore, it can be speculated that neurological phenotypes such as intellectual disability and seizures can be purely caused by CNNM2 variants.
A Multimodal Affinity Fusion Network for Predicting the Survival of Breast Cancer Patients
Authors: Guo Weizhou , Liang Wenbin , Deng Qingchun , Zou Xianchun
Published: August 2021

Accurate survival prediction of breast cancer holds significant meaning for improving patient care. Approaches using multiple heterogeneous modalities such as gene expression, copy number alteration, and clinical data have showed significant advantages over those with only one modality for patient survival prediction. However, existing survival prediction methods tend to ignore the structured information between patients and multimodal data. We propose a multimodal data fusion model based on a novel multimodal affinity fusion network (MAFN) for survival prediction of breast cancer by integrating gene expression, copy number alteration, and clinical data. First, a stack-based shallow self-attention network is utilized to guide the amplification of tiny lesion regions on the original data, which locates and enhances the survival-related features. Then, an affinity fusion module is proposed to map the structured information between patients and multimodal data. The module endows the network with a stronger fusion feature representation and discrimination capability. Finally, the fusion feature embedding and a specific feature embedding from a triple modal network are fused to make the classification of long-term survival or short-term survival for each patient. As expected, the evaluation results on comprehensive performance indicate that MAFN achieves better predictive performance than existing methods. Additionally, our method can be extended to the survival prediction of other cancer diseases, providing a new strategy for other diseases prognosis.
Whole Genome Sequence Data From Captive Baboons Implicate RBFOX1 in Epileptic Seizure Risk
Authors: Kos Mark Z. , Carless Melanie A. , Blondell Lucy , Leland M. Michelle , Knape Koyle D. , Göring Harald H. H. , Szabó Charles Ákos
Published: August 2021

In this study, we investigate the genetic determinants that underlie epilepsy in a captive baboon pedigree and evaluate the potential suitability of this non-human primate model for understanding the genetic etiology of human epilepsy. Archived whole-genome sequence data were analyzed using both a candidate gene approach that targeted variants in baboon homologs of 19 genes (n = 20,881 SNPs) previously implicated in genetic generalized epilepsy (GGE) and a more agnostic approach that examined protein-altering mutations genome-wide as assessed by snpEff (n = 36,169). Measured genotype association tests for baboon cases of epileptic seizure were performed using SOLAR, as well as gene set enrichment analyses (GSEA) and protein–protein interaction (PPI) network construction of top association hits genome-wide (p < 0.01; n = 441 genes). The maximum likelihood estimate of heritability for epileptic seizure in the pedigreed baboon sample is 0.76 (SE = 0.77; p = 0.07). Among candidate genes for GGE, a significant association was detected for an intronic SNP in RBFOX1 (p = 5.92 × 10–6; adjusted p = 0.016). For protein-altering variants, no genome-wide significant results were observed for epilepsy status. However, GSEA revealed significant positive enrichment for genes involved in the extracellular matrix structure (ECM; FDR = 0.0072) and collagen formation (FDR = 0.017), which was reflected in a major PPI network cluster. This preliminary study highlights the potential role of RBFOX1 in the epileptic baboon, a protein involved in transcriptomic regulation of multiple epilepsy candidate genes in humans and itself previously implicated in human epilepsy, both focal and generalized. Moreover, protein-damaging variants from across the genome exhibit a pattern of association that links collagen-containing ECM to epilepsy risk. These findings suggest a shared genetic etiology between baboon and human forms of GGE and lay the foundation for follow-up research.
Interpretable, Scalable, and Transferrable Functional Projection of Large-Scale Transcriptome Data Using Constrained Matrix Decomposition
Authors: Panchy Nicholas , Watanabe Kazuhide , Hong Tian
Published: August 2021

Large-scale transcriptome data, such as single-cell RNA-sequencing data, have provided unprecedented resources for studying biological processes at the systems level. Numerous dimensionality reduction methods have been developed to visualize and analyze these transcriptome data. In addition, several existing methods allow inference of functional variations among samples using gene sets with known biological functions. However, it remains challenging to analyze transcriptomes with reduced dimensions that are interpretable in terms of dimensions’ directionalities, transferrable to new data, and directly expose the contribution or association of individual genes. In this study, we used gene set non-negative principal component analysis (gsPCA) and non-negative matrix factorization (gsNMF) to analyze large-scale transcriptome datasets. We found that these methods provide low-dimensional information about the progression of biological processes in a quantitative manner, and their performances are comparable to existing functional variation analysis methods in terms of distinguishing multiple cell states and samples from multiple conditions. Remarkably, upon training with a subset of data, these methods allow predictions of locations in the functional space using data from experimental conditions that are not exposed to the models. Specifically, our models predicted the extent of progression and reversion for cells in the epithelial-mesenchymal transition (EMT) continuum. These methods revealed conserved EMT program among multiple types of single cells and tumor samples. Finally, we demonstrate this approach is broadly applicable to data and gene sets beyond EMT and provide several recommendations on the choice between the two linear methods and the optimal algorithmic parameters. Our methods show that simple constrained matrix decomposition can produce to low-dimensional information in functionally interpretable and transferrable space, and can be widely useful for analyzing large-scale transcriptome data.
A Cross-Sectional and Longitudinal Study to Define Alarmins and A-SAA Variants as Companion Markers in Early Rheumatoid Arthritis
Authors: Ciregia Federica , Nys Gwenaël , Cobraiville Gaël , Badot Valérie , Di Romana Silvana , Sidiras Paschalis , Sokolova Tatiana , Durez Patrick , Fillet Marianne , Malaise Michel G. , de Seny Dominique
Published: August 2021

Nowadays, in the study of rheumatoid arthritis (RA), more and more interest is directed towards an earlier effective therapeutic intervention and the determination of companion markers for predicting response to therapy with the goal to prevent progressive joint damage, deformities, and functional disability. With the present work, we aimed at quantifying in a cohort of early RA (ERA) patients naïve to DMARD therapy, proteins whose increase was previously found associated with RA: serum amyloid A (A-SAA) and alarmins. Five A-SAA variants (SAA1α, SAA1β, SAA1γ, SAA2α, and SAA2β) but also S100A8 and S100A9 proteins were simultaneously quantified in plasma applying a method based on single targeted bottom-up proteomics LC-MS/MS. First, we compared their expression between ERA (n = 100) and healthy subjects (n = 100), then we focused on their trend by monitoring ERA patients naïve to DMARD treatment, 1 year after starting therapy. Only SAA1α and SAA2α levels were increased in ERA patients, and SAA2α appears to mostly mediate the pathological role of A-SAA. Levels of these variants, together with SAA1β, only decreased under biologic DMARD treatment but not under methotrexate monotherapy. This study highlights the importance to better understand the modulation of expression of these variants in ERA in order to subsequently better characterize their biological function. On the other hand, alarmin expression increased in ERA compared to controls but remained elevated after 12 months of methotrexate or biologic treatment. The work overcomes the concept of considering these proteins as biomarkers for diagnosis, demonstrating that SAA1α, SAA1β, and SAA2α variants but also S100A8 and S100A9 do not respond to all early treatment in ERA and should be rather considered as companion markers useful to improve the follow-up of treatment response and remission state. Moreover, it suggests that earlier use of biologics in addition to methotrexate may be worth considering.
Cytokine Signature Associated With Disease Severity in COVID-19
Authors: Guo Jing , Wang Shuting , Xia He , Shi Ding , Chen Yu , Zheng Shufa , Chen Yanfei , Gao Hainv , Guo Feifei , Ji Zhongkang , Huang Chenjie , Luo Rui , Zhang Yan , Zuo Jian , Chen Yunbo , Xu Yan , Xia Jiafeng , Zhu Chunxia , Xu Xiaowei , Qiu Yunqing , Sheng Jifang , Xu Kaijin , Li Lanjuan
Published: August 2021

Coronavirus disease 2019 (COVID-19) broke out and then became a global epidemic at the end of 2019. With the increasing number of deaths, early identification of disease severity and interpretation of pathogenesis are very important. Aiming to identify biomarkers for disease severity and progression of COVID-19, 75 COVID-19 patients, 34 healthy controls and 23 patients with pandemic influenza A(H1N1) were recruited in this study. Using liquid chip technology, 48 cytokines and chemokines were examined, among which 33 were significantly elevated in COVID-19 patients compared with healthy controls. HGF and IL-1β were strongly associated with APACHE II score in the first week after disease onset. IP-10, HGF and IL-10 were correlated positively with virus titers. Cytokines were significantly correlated with creatinine, troponin I, international normalized ratio and procalcitonin within two weeks after disease onset. Univariate analyses were carried out, and 6 cytokines including G-CSF, HGF, IL-10, IL-18, M-CSF and SCGF-β were found to be associated with the severity of COVID-19. 11 kinds of cytokines could predict the severity of COVID-19, among which IP-10 and M-CSF were excellent predictors for disease severity. In conclusion, the levels of cytokines in COVID-19 were significantly correlated with the severity of the disease in the early stage, and serum cytokines could be used as warning indicators of the severity and progression of COVID-19. Early stratification of disease and intervention to reduce hypercytokinaemia may improve the prognosis of COVID-19 patients.
Emerging Complexity in CD4+T Lineage Programming and Its Implications in Colorectal Cancer
Authors: DiToro Daniel , Basu Rajatava
Published: August 2021

The intestinal immune system has the difficult task of protecting a large environmentally exposed single layer of epithelium from pathogens without allowing inappropriate inflammatory responses. Unmitigated inflammation drives multiple pathologies, including the development of colorectal cancer. CD4+T cells mediate both the suppression and promotion of intestinal inflammation. They comprise an array of phenotypically and functionally distinct subsets tailored to a specific inflammatory context. This diversity of form and function is relevant to a broad array of pathologic and physiologic processes. The heterogeneity underlying both effector and regulatory T helper cell responses to colorectal cancer, and its impact on disease progression, is reviewed herein. Importantly, T cell responses are dynamic; they exhibit both quantitative and qualitative changes as the inflammatory context shifts. Recent evidence outlines the role of CD4+T cells in colorectal cancer responses and suggests possible mechanisms driving qualitative alterations in anti-cancer immune responses. The heterogeneity of T cells in colorectal cancer, as well as the manner and mechanism by which they change, offer an abundance of opportunities for more specific, and likely effective, interventional strategies.
Discovery of Novel Biomarkers for Diagnosing and Predicting the Progression of Multiple Sclerosis Using TMT-Based Quantitative Proteomics
Authors: Shi Yijun , Ding Yaowei , Li Guoge , Wang Lijuan , Osman Rasha Alsamani , Sun Jialu , Qian Lingye , Zheng Guanghui , Zhang Guojun
Published: August 2021

Objective

Here, we aimed to identify protein biomarkers that could rapidly and accurately diagnose multiple sclerosis (MS) using a highly sensitive proteomic immunoassay.

Methods

Tandem mass tag (TMT) quantitative proteomic analysis was performed to determine the differentially expressed proteins (DEPs) in cerebrospinal fluid (CSF) samples collected from 10 patients with MS and 10 non-inflammatory neurological controls (NINCs). The DEPs were analyzed using bioinformatics tools, and the candidate proteins were validated using the ELISA method in another cohort comprising 160 samples (paired CSF and plasma of 40 patients with MS, CSF of 40 NINCs, and plasma of 40 healthy individuals). Receiver operating characteristic (ROC) curves were used to determine the diagnostic potential of this method.

Results

Compared to NINCs, we identified 83 CSF-specific DEPs out of a total of 343 proteins in MS patients. Gene ontology (GO) enrichment analysis revealed that these DEPs are mainly involved in platelet degranulation, negative regulation of proteolysis, and post-translational protein modification. Pathway enrichment analysis revealed that the complement and coagulation cascades, Ras signaling pathway, and PI3K-Akt signaling pathway are the main components. Insulin-like growth factor-binding protein 7 (IGFBP7), insulin-like growth factor 2 (IGF2), and somatostatin (SST) were identified as the potential proteins with high scores, degree, and centrality in the protein-protein interaction (PPI) network. We validated the expression of these three proteins using ELISA. Compared to NINCs, the level of CSF IGFBP7 was significantly upregulated, and the level of CSF SST was significantly downregulated in the MS group.

Conclusion

Our results suggest that SST and IGFBP7 might be associated with the pathogenesis of MS and would be helpful in diagnosing MS. Since IGFBP7 was used to classify relapsing remitting MS (RRMS) and secondary progressive MS (SPMS) patients, therefore, it may act as a potential key marker and therapeutic target in MS.
The Spleen as a Target to Characterize Immunomodulatory Effects of Down-Stream Processed Cyberlindnera jadinii Yeasts in Atlantic Salmon Exposed to a Dietary Soybean Meal Challenge
Authors: Morales-Lange Byron , Agboola Jeleel Opeyemi , Hansen Jon Øvrum , Lagos Leidy , Øyås Ove , Mercado Luis , Mydland Liv Torunn , Øverland Margareth
Published: August 2021

Aquaculture feeds have changed dramatically from being largely based on fishmeal (FM) towards increased use of plant protein sources, which could impact the fish’s immune response. In order to characterize immunomodulatory properties of novel functional ingredients, this study used four diets, one based on FM, a challenging diet with 40% soybean meal (SBM), and two diets containing 40% SBM with 5% of Cyberlindnera jadinii yeast exposed to different down-stream processing conditions: heat-inactivated (ICJ) or autolysation (ACJ). The immunomodulatory effects of the diets were analyzed in the spleen of Atlantic salmon after 37 days of feeding, using a transcriptomic evaluation by RNA sequencing (RNA-seq) and the detection of specific immunological markers at the protein level through indirect Enzyme-linked Immunosorbent Assay (indirect ELISA). The results showed that SBM (compared to FM) induced a down-regulation of pathways related to ion binding and transport, along with an increase at the protein level of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ). On the other hand, while ICJ (compared to FM-group) maintain the inflammatory response associated with SBM, with higher levels of TNFα and IFNγ, and with an upregulation of creatine kinase activity and phosphagen metabolic process, the inclusion of ACJ was able to modulate the response of Atlantic salmon compared to fish fed the SBM-diet by the activation of biological pathways related to endocytosis, Pattern recognition receptor (PPRs)-signal transduction and transporter activity. In addition, ACJ was also able to control the pro-inflammatory profile of SBM, increasing Interleukin 10 (IL-10) levels and decreasing TNFα production, triggering an immune response similar to that of fish fed an FM-based diet. Finally, we suggest that the spleen is a good candidate to characterize the immunomodulatory effects of functional ingredients in Atlantic salmon. Moreover, the inclusion of ACJ in fish diets, with the ability to control inflammatory processes, could be considered in the formulation of sustainable salmon feed.
Pro-Inflammatory Implications of 2-Hydroxypropyl-β-cyclodextrin Treatment
Authors: Houben Tom , Yadati Tulasi , de Kruijf Robbin , Gijbels Marion J. J. , Luiken Joost J. F. P. , van Zandvoort Marc , Kapsokalyvas Dimitris , Lütjohann Dieter , Westerterp Marit , Plat Jogchum , Leake David , Shiri-Sverdlov Ronit
Published: August 2021

Lifestyle- and genetically induced disorders related to disturbances in cholesterol metabolism have shown the detrimental impact of excessive cholesterol levels on a plethora of pathological processes such as inflammation. In this context, two-hydroxypropyl-β-cyclodextrin (CD) is increasingly considered as a novel pharmacological compound to decrease cellular cholesterol levels due to its ability to increase cholesterol solubility. However, recent findings have reported contra-indicating events after the use of CD questioning the clinical applicability of this compound. Given its potential as a therapeutic compound in metabolic inflammatory diseases, in this study, we evaluated the inflammatory effects of CD administration in the context of cholesterol-induced metabolic inflammation in vivo and in vitro. The inflammatory and cholesterol-depleting effects of CD were first investigated in low-density lipoprotein receptor knockout (Ldlr-/) mice that were transplanted with Npc1nih or Npc1wt bone marrow and were fed either regular chow or a high-fat, high-cholesterol (HFC) diet for 12 weeks, thereby creating an extreme model of lysosomal cholesterol-induced metabolic inflammation. In the final three weeks, these mice received daily injections of either control (saline) or CD subcutaneously. Subsequently, the inflammatory properties of CD were investigated in vitro in two macrophage cell lines and in murine bone marrow-derived macrophages (BMDMs). While CD administration improved cholesterol mobilization outside lysosomes in BMDMs, an overall pro-inflammatory profile was observed after CD treatment, evidenced by increased hepatic inflammation in vivo and a strong increase in cytokine release and inflammatory gene expression in vitro in murine BMDMs and macrophages cell lines. Nevertheless, this CD-induced pro-inflammatory profile was time-dependent, as short term exposure to CD did not result in a pro-inflammatory response in BMDM. While CD exerts desired cholesterol-depleting effects, its inflammatory effect is dependent on the exposure time. As such, using CD in the clinic, especially in a metabolic inflammatory context, should be closely monitored as it may lead to undesired, pro-inflammatory side effects.
Natural Killer Cells as Key Mediators in Type I Diabetes Immunopathology
Authors: Gardner Graeme , Fraker Christopher A.
Published: August 2021

The immunopathology of type I diabetes (T1D) presents a complicated case in part because of the multifactorial origin of this disease. Typically, T1D is thought to occur as a result of autoimmunity toward islets of Langerhans, resulting in the destruction of insulin-producing cells (β cells) and thus lifelong reliance on exogenous insulin. However, that explanation obscures much of the underlying mechanism, and the actual precipitating events along with the associated actors (latent viral infection, diverse immune cell types and their roles) are not completely understood. Notably, there is a malfunctioning in the regulation of cytotoxic CD8+ T cells that target endocrine cells through antigen-mediated attack. Further examination has revealed the likelihood of an imbalance in distinct subpopulations of tolerogenic and cytotoxic natural killer (NK) cells that may be the catalyst of adaptive immune system malfunction. The contributions of components outside the immune system, including environmental factors such as chronic viral infection also need more consideration, and much of the recent literature investigating the origins of this disease have focused on these factors. In this review, the details of the immunopathology of T1D regarding NK cell disfunction is discussed, along with how those mechanisms stand within the context of general autoimmune disorders. Finally, the rarer cases of latent autoimmune, COVID-19 (viral), and immune checkpoint inhibitor (ICI) induced diabetes are discussed as their exceptional pathology offers insight into the evolution of the disease as a whole.
Transcriptional, Epigenetic, and Functional Reprogramming of Monocytes From Non-Human Primates Following Chronic Alcohol Drinking
Authors: Lewis Sloan A. , Sureshchandra Suhas , Doratt Brianna , Jimenez Vanessa A. , Stull Cara , Grant Kathleen A. , Messaoudi Ilhem
Published: August 2021

Chronic heavy drinking (CHD) of alcohol is a known risk factor for increased susceptibility to bacterial and viral infection as well as impaired wound healing. Evidence suggests that these defects are mediated by a dysregulated inflammatory response originating from myeloid cells, notably monocytes and macrophages, but the mechanisms remain poorly understood. Our ability to study CHD is impacted by the complexities of human drinking patterns and behavior as well as comorbidities and confounding risk factors for patients with alcohol use disorders. To overcome these challenges, we utilized a translational rhesus macaque model of voluntary ethanol self-administration that closely recapitulates human drinking patterns and chronicity. In this study, we examined the effects of CHD on blood monocytes in control and CHD female macaques after 12 months of daily ethanol consumption. While monocytes from CHD female macaques generated a hyper-inflammatory response to ex vivo LPS stimulation, their response to E. coli was dampened. In depth scRNA-Seq analysis of purified monocytes revealed significant shifts in classical monocyte subsets with accumulation of cells expressing markers of hypoxia (HIF1A) and inflammation (NFkB signaling pathway) in CHD macaques. The increased presence of monocyte subsets skewed towards inflammatory phenotypes was complemented by epigenetic analysis, which revealed higher accessibility of promoter regions that regulate genes involved in cytokine signaling pathways. Collectively, data presented in this manuscript demonstrate that CHD shifts classical monocyte subset composition and primes the monocytes towards a more hyper-inflammatory response to LPS, but compromised pathogen response.
Collaborative Automation and IoT Technologies for Coastal Ocean Observing Systems
Authors: Mariani Patrizio , Bachmayer Ralf , Kosta Sokol , Pietrosemoli Ermanno , Ardelan Murat V. , Connelly Douglas P. , Delory Eric , Pearlman Jay S. , Petihakis George , Thompson Fletcher , Crise Alessandro
Published: August 2021

Coastal observing systems are typically nationally funded and built around national priorities. As a result, there are presently significant differences between countries in terms of sustainability, observing capacity and technologies, as well as methods and research priorities. Ocean observing systems in coastal areas must now move toward an integrated, multidisciplinary and multiscale system of systems, where heterogeneity should be exploited to deliver fit-for-purpose products that answer the diversity and complexity of the requirements from stakeholders and end-users. Essential elements of such distributed observation systems are the use of machine-to-machine communication, data fusion and processing applying recent technological developments for the Internet of Things (IoT) toward a common cyberinfrastructure. This perspective paper illustrates some of the challenges for sustained coastal observations and provides details on how to address present gaps. We discuss the role of collaborative robotics between unmanned platforms in coastal areas and the methods to benefit from IoT technologies. Given present trends in cost-effective solutions in ocean sensors and electronics, and methods for marine automation and communication, we consider that a distributed observation system can effectively provide timely information in coastal regions around the world, including those areas that are today poorly observed (e.g., developing countries). Adaptation in space and time of the sensing nodes, and the flexibility in handling different sensing platforms can provide to the system the ability to quickly respond to the rapid changes in oceanic and climatic processes, as well as to promptly respond to evolving stakeholder and end-user requirements.
Multidecadal Sea Level Variability in the Baltic Sea and Its Impact on Acceleration Estimations
Authors: Agha Karimi Armin , Bagherbandi Mohammad , Horemuz Milan
Published: August 2021

Multidecadal sea level variation in the Baltic Sea is investigated from 1900 to 2020 deploying satellite and in situ datasets. As a part of this investigation, nearly 30 years of satellite altimetry data are used to compare with tide gauge data in terms of linear trend. This, in turn, leads to validation of the regional uplift model developed for the Fennoscandia. The role of North Atlantic Oscillation (NAO) in multidecadal variations of the Baltic Sea is also analyzed. Although NAO impacts the Baltic Sea level on seasonal to decadal time scales according to previous studies, it is not a pronounced factor in the multidecadal variations. The acceleration in the sea level rise of the basin is reported as statistically insignificant in recent studies or even decelerating in an investigation of the early 1990s. It is shown that the reason for these results relates to the global warming hiatus in the 1950s−1970s, which can be seen in all eight tide gauges used for this study. To account for the slowdown period, the acceleration in the basin is investigated by fitting linear trends to time spans of six to seven decades, which include the hiatus. These results imply that the sea level rise is accelerated in the Baltic Sea during the period 1900–2020.
A Steady Regime of Volume and Heat Transports in the Eastern Arctic Ocean in the Early 21st Century
Authors: Pnyushkov A. V. , Polyakov I. V. , Alekseev G. V. , Ashik I. M. , Baumann T. M. , Carmack E. C. , Ivanov V. V. , Rember R.
Published: August 2021

Mooring observations in the eastern Eurasian Basin of the Arctic Ocean showed that mean 2013–2018 along-slope volume and heat (calculated relative to the freezing temperature) transports in the upper 800 m were 4.8 ± 0.1 Sv (1 Sv = 106 m3/s) and 34.8 ± 0.6 TW, respectively. Volume and heat transports within the Atlantic Water (AW) layer (∼150–800 m) in 2013–2018 lacked significant temporal shifts at annual and longer time scales: averaged over the two periods of mooring deployment in 2013–2015 and 2015–2018, volume transports were 3.1 ± 0.1 Sv, while AW heat transports were 31.3 ± 1.0 TW and 34.8 ± 0.8 TW. Moreover, the reconstructed AW volume transports over longer, 2003–2018, period of time showed strong interannual variations but lacked a statistically significant trend. However, we found a weak positive trend of 0.08 ± 0.07 Sv/year in the barotropic AW volume transport estimated using dynamic ocean topography (DOT) measurements in 2003–2014 – the longest period spanned by the DOT dataset. Vertical coherence of 2013–2018 transports in the halocline (70–140 m) and AW (∼150–800 m) layers was high, suggesting the essential role of the barotropic forcing in constraining along-slope transports. Quantitative estimates of transports and their variability discussed in this study help identify the role of atlantification in critical changes of the eastern Arctic Ocean.
Bioavailability of Various Phosphorus Fractions and Their Seasonality in a Eutrophic Estuary in the Southern Baltic Sea – A Laboratory Approach
Authors: Rönspieß Lisa , Nausch Günther , Schulz-Bull Detlef
Published: August 2021

Phosphorus (P) is a major driver of eutrophication, especially in anthropogenically impacted coastal waters, and determining its bioavailability is important for providing a good estimation of the eutrophication potential in aquatic systems. Therefore, we observed the bioavailability of P in four laboratory experiments on water samples collected in March, June, September, and December 2018. In the experiments, all P fractions of the sampled water were investigated in three treatments (“unfiltered” and “10 μm”- and “1.2 μm”-filtered). The bioavailability (utilization by organisms within several days) ranged from 9 to 100% for dissolved P, and 34 to 100% for particulate P. However, one of the particulate P fractions was bound in biomass and therefore was not directly bioavailable. The conditions in the March experiment represented a natural spring bloom with a residual potential for planktonic growth. In June and September, the nutrients needed for growth were depleted in the different treatments. In December, a spring bloom was simulated by the laboratory conditions. Preferential P uptake by a specific group of organisms could not be observed directly, although a trend of higher utilization of dissolved P by heterotrophic bacteria was observed. In conclusion, the bioavailable P (sum of dissolved P fractions and one particulate P fraction) accounted for between 20 and 94% of the total P. Consequently, our experiments demonstrated that the commonly monitored P fractions lead to an underestimation of the bioavailable P and thus of potential for eutrophication in aquatic systems, too.
Ecological Constraint Mapping: Understanding Outcome-Limiting Bottlenecks for Improved Environmental Decision-Making in Marine and Coastal Environments
Authors: Sheaves Marcus , Mattone Carlo , Connolly Rod M. , Hernandez Stephanie , Nagelkerken Ivan , Murray Nicholas , Ronan Michael , Waltham Nathan John , Bradley Michael
Published: August 2021

Despite genuine attempts, the history of marine and coastal ecosystem management is littered with examples of poor environmental, social and financial outcomes. Marine ecosystems are largely populated by species with open populations, and feature ecological processes that are driven by multiple, interwoven, dynamic causes and effects. This complexity limits the acquisition of relevant knowledge of habitat characteristics, species utilisation and ecosystem dynamics. The consequence of this lack of knowledge is uncertainty about the link between action taken and outcome achieved. Such uncertainty risks misdirected human and financial investment, and sometimes may even lead to perverse outcomes. Technological advances offer new data acquisition opportunities, but the diversity and complexity of the biological and ecological information needed to reduce uncertainty means the increase in knowledge will be slow unless it is undertaken in a structured and focussed way. We introduce “Ecological Constraint Mapping” – an approach that takes a “supply chain” point of view and focusses on identifying the principal factors that constrain life-history outcomes (success/productivity/resilience/fitness) for marine and coastal species, and ultimately the quality and resilience of the ecosystems they are components of, and the life-history supporting processes and values ecosystems provide. By providing a framework for the efficient development of actionable knowledge, Ecological Constraint Mapping can facilitate a move from paradigm-based to knowledge-informed decision-making on ecological issues. It is suitable for developing optimal solutions to a wide range of conservation and management problems, providing an organised framework that aligns with current perspectives on the complex nature of marine and coastal systems.
Hierarchical Structure Fabrication of IPMC Strain Sensor With High Sensitivity
Authors: Chang Longfei , Wang Dongping , Hu Jiajia , Li Yan , Wang Yanjie , Hu Ying
Published: August 2021

In this paper, a biological template method is introduced and investigated to fabricate ionic polymer-metal composite (IPMC) strain sensor with bionic hierarchical structures. We utilized the multi-level structure of reed leaf surface, which can improve the contact area between the substrate and the electrode layers. Hierarchical structures were observed on the IPMC samples, including pyramid strips with the width in the range of 60–80 μm as well as synaptic scatters with diameter around 10 μm. In addition, five kinds of sensors with different interface structures were obtained by combining the traditional microneedle roller roughening and chemical plating processes. It was found that the IPMC sensor with reed-leaf and microneedle structure on each side presented the best performance, along with a high linearity, a sensitivity of 62.5 mV/1% and a large generated voltage peak under given mechanical stimuli, which is 3.7 times that of the sample fabricated without roughening.
Acid pH Increases SARS-CoV-2 Infection and the Risk of Death by COVID-19
Authors: Jimenez Leandro , Campos Codo Ana , Sampaio Vanderson de Souza , Oliveira Antonio E. R. , Ferreira Lucas Kaoru Kobo , Davanzo Gustavo Gastão , Brito Monteiro Lauar de , Victor Virgilio-da-Silva João , Borba Mayla Gabriela Silva , Fabiano de Souza Gabriela , Zini Nathalia , Andrade Gandolfi Flora de , Muraro Stéfanie Primon , Luiz Proença-Modena José , Val Fernando Almeida , Cardoso Melo Gisely , Monteiro Wuelton Marcelo , Nogueira Maurício Lacerda , Lacerda Marcus Vinícius Guimarães , Moraes-Vieira Pedro M. , Nakaya Helder I.
Published: August 2021

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect a broad range of human tissues by using the host receptor angiotensin-converting enzyme 2 (ACE2). Individuals with comorbidities associated with severe COVID-19 display higher levels of ACE2 in the lungs compared to those without comorbidities, and conditions such as cell stress, elevated glucose levels and hypoxia may also increase the expression of ACE2. Here, we showed that patients with Barrett's esophagus (BE) have a higher expression of ACE2 in BE tissues compared to normal squamous esophagus, and that the lower pH associated with BE may drive this increase in expression. Human primary monocytes cultured in reduced pH displayed increased ACE2 expression and higher viral load upon SARS-CoV-2 infection. We also showed in two independent cohorts of 1,357 COVID-19 patients that previous use of proton pump inhibitors is associated with 2- to 3-fold higher risk of death compared to those not using the drugs. Our work suggests that pH has a great influence on SARS-CoV-2 Infection and COVID-19 severity.
The Association in Myopic Tractional Maculopathy With Myopic Atrophy Maculopathy
Authors: Tian Jiaxin , Qi Yue , Lin Caixia , Cao Kai , Wang Ningli
Published: August 2021

Purpose: To investigate the relationship between myopic tractional maculopathy (MTM) and myopic atrophy maculopathy (MAM).

Method: Two hundred and six eyes with definitive myopic retinoschisis were assessed in the retrospective observational case series study and the atrophic and tractional features were further evaluated. Atrophic changes were analyzed according to the atrophic component in the ATN classification and the occurrence of gamma zones and delta zones. Tractional changes were evaluated based on different retinoschisis layers, the location and range of outer retinoschisis, retinal detachment, inner lamellar macular hole (ILMH), outer lamellar MH (OLMH), full-thickness MH (FTMH), and paravascular abnormalities.

Results: Of all the eyes, 29.6, 42.7, 19.4, and 8.3% presented MAM grades with A1, A2, A3, and A4, respectively. The three layers of retinoschisis and the entire macular retinoschisis had the highest incidences in A2 (38.6%; 54.5%). The numbers of retinoschisis layers and the grades of outer retinoschisis had a weak negative correlation with MAM (r = −0.138, P = 0.048; r = −0.139, P = 0.047). All the eyes had gamma zones, and 82.52% of eyes also had delta zones. The incidence of retinal detachment and OLMH reached the peak in A2 and then decreased gradually. With MAM aggravation, the prevalence of ILMH decreased. Eyes with A1 and A2 were more likely to have OLMH, and those with A3 and A4 were more likely to have FTMH (P = 0.028; OR, 3.423; 95% CI, 1.144–10.236; P = 0.004; OR, 7.752; 95% CI, 1.951–30.803). With the MAM grades growing, the types of paravascular abnormalities increased (r = 0.165, P = 0.018).

Conclusion: Diffuse chorioretinal atrophy was the dominant MAM grade in eyes with MTM. In the study, 72.3% of eyes with MTM presented with diffuse chorioretinal atrophy and a tessellated fundus. Over 80% of eyes with MTM had both gamma zones and delta zones. Diffuse chorioretinal atrophy might be a complicated stage for MTM with the highest rate of three layers of retinoschisis, the entire macular retinoschisis, RD, and OLMH. Atrophic progression might involve the development of MH. When MTM combines with well-defined atrophy, the occurrence of FTMH should be noted.
Risk of Reactivation of Hepatitis B Virus (HBV) and Tuberculosis (TB) and Complications of Hepatitis C Virus (HCV) Following Tocilizumab Therapy: A Systematic Review to Inform Risk Assessment in the COVID-19 Era
Authors: Campbell Cori , Andersson Monique I. , Ansari M. Azim , Moswela Olivia , Misbah Siraj A. , Klenerman Paul , Matthews Philippa C.
Published: August 2021

Objectives:Tocilizumab (TCZ), an IL-6 receptor antagonist, is used in the treatment of severe COVID-19 caused by infection with SARS-CoV-2. However, unintended consequences of TCZ therapy include reactivation of tuberculosis (TB) or hepatitis B virus (HBV), and worsening of hepatitis C virus (HCV). We set out to assimilate existing data for these complications, in order to help inform evidence-based risk assessments for the use of TCZ, and thus to reduce the risk of serious but preventable complications.

Methods:We searched the global WHO database of Individual Case Safety Reports (ICSRs) and adverse drug reactions (ADRs) (“VigiBase”) and undertook a systematic literature review, in accordance with PRISMA guidelines. We generated mean cumulative incidence estimates for infection complications.

Results:Mean cumulative incidence of HBV and TB were 3.3 and 4.3%, respectively, in patients receiving TCZ. Insufficient data were available to generate estimates for HCV. These estimates derive from heterogeneous studies pre-dating SARS-CoV-2, with differing epidemiology and varied approaches to screening and prophylaxis, so formal meta-analysis was not possible.

Conclusions:We underline the need for careful individual risk assessment prior to TCZ prescription, and present an algorithm to guide clinical stratification. There is an urgent need for ongoing collation of safety data as TCZ therapy is used in COVID.
Citrus Segment Degradation Potential, Enzyme Safety Evaluation, and Whole Genome Sequence of Aspergillus aculeatus Strain ZC-1005
Authors: Wang Jieyi , Gao Zhipeng , Qian Yujiao , Hu Xiao , Li Gaoyang , Fu Fuhua , Guo Jiajing , Shan Yang
Published: August 2021

Aspergillus aculeatus ZC-1005 (ZC-1005 was used as the abbreviation of this strain) is a hemicellulase-producing strain isolated from rotten citrus rind buried in the soil. Our previous study has shown its biochemical properties including high xylanase activity, mannanase activity, and degradation reaction with citrus mesocarp. In this study, we focused more on the enzyme safety evaluation and the genome sequencing via PacBio and Illumina platforms. High biological safety of the crude enzymes of ZC-1005 has been proven by the acute oral toxicity test, sub-chronic toxicity test, micronucleus test, and sperm malformation test. The genome of ZC-1005 had a GC content of 52.53%, with a size of 35,458,484 bp, and encoded 10,147 genes. Strain ZC-1005 harbored 269 glycosyl hydrolase (GH) genes of 64 families. The fungus produces cellulose-acting (GH3, GH5, GH12, and GH1) and hemicellulose-acting enzymes (GH16, GH31, GH2, and GH92). In genome annotation, we paid more attention to the genes encoding xylanase, such as gene 01512, gene 05833, gene 05469, gene 07781, gene 08432, gene 09042, gene 08008, and gene 09694. The collaboration between complete genome information and the degradation test confirmed that ZC-1005 could degrade cellulose and xylan. Our results showed that the citrus enzymatic decapsulation technology was efficacious and safe for canned citrus product processing, which may also solve the industrial waste problem. Therefore, ZC-1005 and the crude enzyme secreted from the strain were very promising to be used in the citrus processing industry.
Genome Sequencing and Comparative Genomics of Indian Isolates of Brucella melitensis
Authors: Karthik Kumaragurubaran , Anbazhagan Subbaiyan , Thomas Prasad , Ananda Chitra Murugesan , Senthilkumar Tuticorin Maragatham Alagesan , Sridhar Ramaswamy , Dhinakar Raj Gopal
Published: August 2021

Brucella melitensis causes small ruminant brucellosis and a zoonotic pathogen prevalent worldwide. Whole genome phylogeny of all available B. melitensis genomes (n = 355) revealed that all Indian isolates (n = 16) clustered in the East Mediterranean lineage except the ADMAS-GI strain. Pangenome analysis indicated the presence of limited accessory genomes with few clades showing specific gene presence/absence pattern. A total of 43 virulence genes were predicted in all the Indian strains of B. melitensis except 2007BM-1 (ricA and wbkA are absent). Multilocus sequence typing (MLST) analysis indicated all except one Indian strain (ADMAS-GI) falling into sequence type (ST 8). In comparison with MLST, core genome phylogeny indicated two major clusters (>70% bootstrap support values) among Indian strains. Clusters with <70% bootstrap support values represent strains with diverse evolutionary origins present among animal and human hosts. Genetic relatedness among animal (sheep and goats) and human strains with 100% bootstrap values shows its zoonotic transfer potentiality. SNP-based analysis indicated similar clustering to that of core genome phylogeny. Among the Indian strains, the highest number of unique SNPs (112 SNPs) were shared by a node that involved three strains from Tamil Nadu. The node SNPs involved several peptidase genes like U32, M16 inactive domain protein, clp protease family protein, and M23 family protein and mostly represented non-synonymous (NS) substitutions. Vaccination has been followed in several parts of the world to prevent small ruminant brucellosis but not in India. Comparison of Indian strains with vaccine strains showed that M5 is genetically closer to most of the Indian strains than Rev.1 strain. The presence of most of the virulence genes among all Indian strains and conserved core genome compositions suggest the use of any circulating strain/genotypes for the development of a vaccine candidate for small ruminant brucellosis in India.
Harnessing the CRISPR-Cas Systems to Combat Antimicrobial Resistance
Authors: Duan Cheng , Cao Huiluo , Zhang Lian-Hui , Xu Zeling
Published: August 2021

The emergence of antimicrobial-resistant (AMR) bacteria has become one of the most serious threats to global health, necessitating the development of novel antimicrobial strategies. CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) system, known as a bacterial adaptive immune system, can be repurposed to selectively target and destruct bacterial genomes other than invasive genetic elements. Thus, the CRISPR-Cas system offers an attractive option for the development of the next-generation antimicrobials to combat infectious diseases especially those caused by AMR pathogens. However, the application of CRISPR-Cas antimicrobials remains at a very preliminary stage and numerous obstacles await to be solved. In this mini-review, we summarize the development of using type I, type II, and type VI CRISPR-Cas antimicrobials to eradicate AMR pathogens and plasmids in the past a few years. We also discuss the most common challenges in applying CRISPR-Cas antimicrobials and potential solutions to overcome them.