bluuebunny/crossref_metadata_2025 huggingface dataset:
Collective Cell Migration in a Fibrous Environment: A Hybrid Multiscale Modelling Approach
Authors: Suveges Szabolcs , Chamseddine Ibrahim , Rejniak Katarzyna A. , Eftimie Raluca , Trucu Dumitru
Published: June 2021

The specific structure of the extracellular matrix (ECM), and in particular the density and orientation of collagen fibres, plays an important role in the evolution of solid cancers. While many experimental studies discussed the role of ECM in individual and collective cell migration, there are still unanswered questions about the impact of nonlocal cell sensing of other cells on the overall shape of tumour aggregation and its migration type. There are also unanswered questions about the migration and spread of tumour that arises at the boundary between different tissues with different collagen fibre orientations. To address these questions, in this study we develop a hybrid multi-scale model that considers the cells as individual entities and ECM as a continuous field. The numerical simulations obtained through this model match experimental observations, confirming that tumour aggregations are not moving if the ECM fibres are distributed randomly, and they only move when the ECM fibres are highly aligned. Moreover, the stationary tumour aggregations can have circular shapes or irregular shapes (with finger-like protrusions), while the moving tumour aggregations have elongate shapes (resembling to clusters, strands or files). We also show that the cell sensing radius impacts tumour shape only when there is a low ratio of fibre to non-fibre ECM components. Finally, we investigate the impact of different ECM fibre orientations corresponding to different tissues, on the overall tumour invasion of these neighbouring tissues.
Performance-Based Coastal Engineering Framework
Authors: González-Dueñas Catalina , Padgett Jamie E.
Published: June 2021

The changing dynamics of coastal regions and climate pose severe challenges to coastal communities around the world. Effective planning of engineering projects and resilience strategies in coastal regions must not only address current conditions but also take into consideration the expected changes in the exposure and multi-hazard risk in these areas. However, existing performance-based engineering frameworks generally neglect time-varying factors and miss the opportunity to leverage related evidence as it becomes available. This paper proposes a Performance-Based Coastal Engineering (PBCE) framework that is flexible enough to accommodate uncertain time-varying factors, multi-hazard conditions, and cascading-effects. Furthermore, using a dynamic Bayesian network approach, the framework can incorporate observed evidence into the model to update the prior conditional distribution of the analyzed variables. As a proof of concept, two case studies—a typical elevated residential structure and a two-frame system—are presented, considering the effects of cascading failure, the incorporation of time-varying factors, and the influence of emerging evidence. Results show that neglecting cascading effects significantly underestimates the losses and that the incorporation of evidence reduces the uncertainty under the assumed distribution of evidence. The resulting PBCE framework can support data collection efforts, optimization of retrofitting strategies, integration of experts and community interests by facilitating interactions and knowledge sharing, as well as the identification of vulnerable regions and critical components in coastal multi-hazard regions.
Comprehensive Analysis of the Transcriptome-Wide m6A Methylome in Pterygium by MeRIP Sequencing
Authors: Jiang Yaping , Zhang Xin , Zhang Xiaoyan , Zhao Kun , Zhang Jing , Yang Chuanxi , Chen Yihui
Published: June 2021

Aim

Pterygium is a common ocular surface disease, which is affected by a variety of factors. Invasion of the cornea can cause severe vision loss. N6-methyladenosine (m6A) is a common post-transcriptional modification of eukaryotic mRNA, which can regulate mRNA splicing, stability, nuclear transport, and translation. To our best knowledge, there is no current research on the mechanism of m6A in pterygium.

Methods

We obtained 24 pterygium tissues and 24 conjunctival tissues from each of 24 pterygium patients recruited from Shanghai Yangpu Hospital, and the level of m6A modification was detected using an m6A RNA Methylation Quantification Kit. Expression and location of METTL3, a key m6A methyltransferase, were identified by immunostaining. Then we used m6A-modified RNA immunoprecipitation sequencing (MeRIP-seq), RNA sequencing (RNA-seq), and bioinformatics analyses to compare the differential expression of m6A methylation in pterygium and normal conjunctival tissue.

Results

We identified 2,949 dysregulated m6A peaks in pterygium tissue, of which 2,145 were significantly upregulated and 804 were significantly downregulated. The altered m6A peak of genes were found to play a key role in the Hippo signaling pathway and endocytosis. Joint analyses of MeRIP-seq and RNA-seq data identified 72 hypermethylated m6A peaks and 15 hypomethylated m6A peaks in mRNA. After analyzing the differentially methylated m6A peaks and synchronously differentially expressed genes, we searched the Gene Expression Omnibus database and identified five genes related to the development of pterygium (DSP, MXRA5, ARHGAP35, TMEM43, and OLFML2A).

Conclusion

Our research shows that m6A modification plays an important role in the development of pterygium and can be used as a potential new target for the treatment of pterygium in the future.
Individual Differences in the Use of Acoustic-Phonetic Versus Lexical Cues for Speech Perception
Authors: Giovannone Nikole , Theodore Rachel M.
Published: June 2021

Previous research suggests that individuals with weaker receptive language show increased reliance on lexical information for speech perception relative to individuals with stronger receptive language, which may reflect a difference in how acoustic-phonetic and lexical cues are weighted for speech processing. Here we examined whether this relationship is the consequence of conflict between acoustic-phonetic and lexical cues in speech input, which has been found to mediate lexical reliance in sentential contexts. Two groups of participants completed standardized measures of language ability and a phonetic identification task to assess lexical recruitment (i.e., a Ganong task). In the high conflict group, the stimulus input distribution removed natural correlations between acoustic-phonetic and lexical cues, thus placing the two cues in high competition with each other; in the low conflict group, these correlations were present and thus competition was reduced as in natural speech. The results showed that 1) the Ganong effect was larger in the low compared to the high conflict condition in single-word contexts, suggesting that cue conflict dynamically influences online speech perception, 2) the Ganong effect was larger for those with weaker compared to stronger receptive language, and 3) the relationship between the Ganong effect and receptive language was not mediated by the degree to which acoustic-phonetic and lexical cues conflicted in the input. These results suggest that listeners with weaker language ability down-weight acoustic-phonetic cues and rely more heavily on lexical knowledge, even when stimulus input distributions reflect characteristics of natural speech input.
Circle the Cardiac Remodeling With circRNAs
Authors: Yang Tiqun , Long Tianxin , Du Tailai , Chen Yili , Dong Yugang , Huang Zhan-Peng
Published: June 2021

Cardiac remodeling occurs after the heart is exposed to stress, which is manifested by pathological processes such as cardiomyocyte hypertrophy and apoptosis, dendritic cells activation and cytokine secretion, proliferation and activation of fibroblasts, and finally leads to heart failure. Circular RNAs (circRNAs) are recently recognized as a specific type of non-coding RNAs that are expressed in different species, in different stages of development, and in different pathological conditions. Growing evidences have implicated that circRNAs play important regulatory roles in the pathogenesis of a variety of cardiovascular diseases. In this review, we summarize the biological origin, characteristics, functional classification of circRNAs and their regulatory functions in cardiomyocytes, endothelial cells, fibroblasts, immune cells, and exosomes in the pathogenesis of cardiac remodeling.
Porting HEP Parameterized Calorimeter Simulation Code to GPUs
Authors: Dong Zhihua , Gray Heather , Leggett Charles , Lin Meifeng , Pascuzzi Vincent R. , Yu Kwangmin
Published: June 2021

The High Energy Physics (HEP) experiments, such as those at the Large Hadron Collider (LHC), traditionally consume large amounts of CPU cycles for detector simulations and data analysis, but rarely use compute accelerators such as GPUs. As the LHC is upgraded to allow for higher luminosity, resulting in much higher data rates, purely relying on CPUs may not provide enough computing power to support the simulation and data analysis needs. As a proof of concept, we investigate the feasibility of porting a HEP parameterized calorimeter simulation code to GPUs. We have chosen to use FastCaloSim, the ATLAS fast parametrized calorimeter simulation. While FastCaloSim is sufficiently fast such that it does not impose a bottleneck in detector simulations overall, significant speed-ups in the processing of large samples can be achieved from GPU parallelization at both the particle (intra-event) and event levels; this is especially beneficial in conditions expected at the high-luminosity LHC, where extremely high per-event particle multiplicities will result from the many simultaneous proton-proton collisions. We report our experience with porting FastCaloSim to NVIDIA GPUs using CUDA. A preliminary Kokkos implementation of FastCaloSim for portability to other parallel architectures is also described.
Effectiveness and Adverse Effects of Over-the-Counter Whitening Products on Dental Tissues
Authors: de Freitas Maiara Rodrigues , de Carvalho Marynara Mathias , Liporoni Priscila Christiane Suzy , Fort Ana Clara Borges , Moura Rodrigo de Morais e , Zanatta Rayssa Ferreira
Published: June 2021

The role of bleaching agents (e.g., hydrogen peroxide) in tooth bleaching is quite well-described in a few literature studies and considered as the option choice for those desiring brighter teeth, but alternative methods have emerged to fulfill the desire of patients in a faster, easier, and cheaper way. In this context, whitening over-the-counter (OTC) products are available in several vehicles, such as toothpaste, rinses, gums, paint-on varnishes, and strips, but their effectiveness in terms of bleaching is questioned. This review aimed to describe their mode of action, whitening effectiveness, and harmful effects associated with the indiscriminate use of these products. Dentifrices usually present a combination of abrasives that can induce damage to the tooth surface without evidence of promoting real bleaching. The same was found for rinses, which might present a low pH, with an erosive potential. Charcoal has been included in the composition of these products to improve their whitening effect but there is no evidence supporting it. Regarding strips, they present hydrogen peroxide in a variety of concentrations and are the only OTC products able to promote bleaching. Despite the vehicle, an indication for the use of these products should be made after a careful individual diagnosis of the etiology of the dental staining, considering that most of them seem to be effective only in removing extrinsic stains or preventing their formation over enamel. Also, their indiscriminate use might induce damage and deleterious effects over tooth tissues or gingival tissues. The dentist should be aware of the composition and mode of action of each individual product as they change according to the composition and the vehicle used to recommend the best mode of usage. Still, there is no sound evidence that any of the described OTC products promote a better bleaching effect than the products indicated for a professional.
A Baseline Evaluation of Bioinformatics Capacity in Tanzania Reveals Areas for Training
Authors: Sangeda Raphael Zozimus , Mwakilili Aneth David , Masamu Upendo , Nkya Siana , Mwita Liberata Alexander , Massawe Deogracious Protas , Lyantagaye Sylvester Leonard , Makani Julie
Published: June 2021

Due to the insufficient human and infrastructure capacity to use novel genomics and bioinformatics technologies, Sub-Saharan Africa countries have not entirely ripped the benefits of these technologies in health and other sectors. The main objective of this study was to map out the interest and capacity for conducting bioinformatics and related research in Tanzania. The survey collected demographic information like age group, experience, seniority level, gender, number of respondents per institution, number of publications, and willingness to join the community of practice. The survey also investigated the capacity of individuals and institutions about computing infrastructure, operating system use, statistical packages in use, the basic Microsoft packages experience, programming language experience, bioinformatics tools and resources usage, and type of analyses performed. Moreover, respondents were surveyed about the challenges they faced in implementing bioinformatics and their willingness to join the bioinformatics community of practice in Tanzania. Out of 84 respondents, 50 (59.5%) were males. More than half of these 44 (52.4%) were between 26–32 years. The majority, 41 (48.8%), were master’s degree holders with at least one publication related to bioinformatics. Eighty (95.2%) were willing to join the bioinformatics network and initiative in Tanzania. The major challenge faced by 22 (26.2%) respondents was the lack of training and skills. The most used resources for bioinformatics analyses were BLAST, PubMed, and GenBank. Most respondents who performed analyses included sequence alignment and phylogenetics, which was reported by 57 (67.9%) and 42 (50%) of the respondents, respectively. The most frequently used statistical software packages were SPSS and R. A quarter of the respondents were conversant with computer programming. Early career and young scientists were the largest groups of responders engaged in bioinformatics research and activities across surveyed institutions in Tanzania. The use of bioinformatics tools for analysis is still low, including basic analysis tools such as BLAST, GenBank, sequence alignment software, Swiss-prot and TrEMBL. There is also poor access to resources and tools for bioinformatics analyses. To address the skills and resources gaps, we recommend various modes of training and capacity building of relevant bioinformatics skills and infrastructure to improve bioinformatics capacity in Tanzania.
Psychometric Properties of the Elementary Social Behavior Assessment in Swedish Primary School: A Teacher Rated Index of Students’ Prosocial School Behaviors
Authors: Wikman Carina , Allodi Mara Westling , Ferrer-Wreder Laura
Published: June 2021

This study examined the psychometric properties of a Swedish language adaption of the teacher-rated Elementary Social Behavior Assessment (ESBA), which provides an index of students’ prosocial school behaviors. Participants were eight teachers (two teachers per school in four schools) who rated their students (N = 143 children, M age = 8 years old). The ESBA factor structure was tested with Confirmatory Factor Analysis in a series of models. The two- and three-factor models showed better fit. ESBA showed high internal consistency at the observed level. ESBA’s psychometric properties show initial promise as a tool to help Swedish teachers to support students’ prosocial skills development.
Utilizing Evidence-Centered Design to Develop Assessments: A High School Introductory Computer Science Course
Authors: Newton Sunni , Alemdar Meltem , Rutstein Daisy , Edwards Doug , Helms Michael , Hernandez Diley , Usselman Marion
Published: June 2021

Evidence-centered design (ECD) is an assessment framework tailored to provide structure and rigor to the assessment development process, and also to generate evidence of assessment validity by tightly coupling assessment tasks with focal knowledge, skills, and abilities (FKSAs). This framework is particularly well-suited to FKSAs that are complex and multi-part (Mislevy and Haertel, 2006), as is the case with much of the focal content within the computer science (CS) domain. This paper presents an applied case of ECD used to guide assessment development in the context of a redesigned introductory CS curriculum. In order to measure student learning of CS skills and content taught through the curriculum, knowledge assessments were written and piloted. The use of ECD provided an organizational framework for assessment development efforts, offering assessment developers a clear set of steps with accompanying documentation and decision points, as well as providing robust validity evidence for the assessment. The description of an application of ECD for assessment development within the context of an introductory CS course illustrates its utility and effectiveness, and also provides a guide for researchers carrying out related work.
Type 2 Diabetes Coagulopathy Proteins May Conflict With Biomarkers Reflective of COVID-19 Severity
Authors: Moin Abu Saleh Md , Al-Qaissi Ahmed , Sathyapalan Thozhukat , Atkin Stephen L. , Butler Alexandra E.
Published: June 2021

Objective

Detailed proteomic analysis in a cohort of patients with differing severity of COVID-19 disease identified biomarkers within the complement and coagulation cascades as biomarkers for disease severity has been reported; however, it is unclear if these proteins differ sufficiently from other conditions to be considered as biomarkers.

Methods

A prospective, parallel study in T2D (n = 23) and controls (n = 23). A hyperinsulinemic clamp was performed and normoglycemia induced in T2D [4.5 ± 0.07 mmol/L (81 ± 1.2 mg/dl)] for 1-h, following which blood glucose was decreased to ≤2.0 mmol/L (36 mg/dl). Proteomic analysis for the complement and coagulation cascades were measured using Slow Off-rate Modified Aptamer (SOMA)-scan.

Results

Thirty-four proteins were measured. At baseline, 4 of 18 were found to differ in T2Dversuscontrols for platelet degranulation [Neutrophil-activating peptide-2 (p = 0.014), Thrombospondin-1 (p = 0.012), Platelet factor-4 (p = 0.007), and Kininogen-1 (p = 0.05)], whilst 3 of 16 proteins differed for complement and coagulation cascades [Coagulation factor IX (p < 0.05), Kininogen-1 (p = 0.05), and Heparin cofactor-2 (p = 0.007)]; STRING analysis demonstrated the close relationship of these proteins to one another. Induced euglycemia in T2D showed no protein changesversusbaseline. At hypoglycemia, however, four proteins changed in controls from baseline [Thrombospondin-1 (p < 0.014), platelet factor-4 (p < 0.01), Platelet basic protein (p < 0.008), and Vitamin K-dependent protein-C (p < 0.00003)], and one protein changed in T2D [Vitamin K-dependent protein-C, (p < 0.0002)].

Conclusion

Seven of 34 proteins suggested to be biomarkers of COVID-19 severity within the platelet degranulation and complement and coagulation cascades differed in T2Dversuscontrols, with further changes occurring at hypoglycemia, suggesting that validation of these biomarkers is critical. It is unclear if these protein changes in T2D may predict worse COVID-19 disease for these patients.

Clinical Trial Registration

https://clinicaltrials.gov/, identifier NCT03102801.
Options for Improved Treatment of Saline Wastewater From Fish and Shellfish Processing
Authors: Anh Hoang Thi Hong , Shahsavari Esmaeil , Bott Nathan J. , Ball Andrew S.
Published: June 2021

The rapid growth of the aquaculture industry over recent decades, with annual production reaching 94.6 million tonnes in 2018 has resulted in a significant increase in saline wastewater following the use of seawater in both fish and shellfish production and processing. This wastewater contains high concentrations of nutrients, organic compounds, and total nitrogen, resulting in the requirement for significant treatment prior to discharge to meet environmental regulations, which are becoming more stringent. The infrastructure and running costs associated with physico-chemical treatment approaches are generally higher than the implementation of biological approaches; the latter represents both an economic and sustainable technology. However, salinity represents a significant inhibitor to microbial activity, affecting the efficacy of the biological treatment of wastewater. This review aims to 1) identify the major biodegradable components in saline fish wastewater that may result in deleterious effects upon discharge, 2) discuss the current methods used for the treatment of fish processing wastewaters, and 3) identify opportunities for improved processes to be utilised and identify gaps in knowledge that require further research. Total suspended solids (TSS), chemical oxygen demand (COD), biochemical oxygen demand (BOD), and total nitrogen (TN) were found to be the most prevalent components in fish effluent. High concentrations of TSS and TN are likely due to the protein content. One method for reducing the environmental impact of the treated wastewater is to enhance nutrient removal (TSS, TN, BOD) through process modification, leading to an increase in active proteolytic activity. Bioaugmentation using immobilised, saline-tolerant proteases or halophilic, protease-producing microorganisms have both shown significant potential in laboratory studies in reducing both the COD and TN content of fish processing wastewater to below discharge limits and therefore may represent commercial options for future treatment processes.
Research on the Impact of Green Technology Innovation on Energy Total Factor Productivity, Based on Provincial Data of China
Authors: Wang Mengxin , Li Yanling , Liao Gaoke
Published: June 2021

Against the background of carbon peaking and carbon neutralization, green technology innovation plays an important role in promoting the energy total factor productivity (TFP). This study verifies the impact of green technology innovation on energy TFP in a complete sample and the subsamples by region, by constructing a panel threshold model, and analyzes its influence mechanism on the basis of the mediating effect test based on annual provincial data of mainland China from 2005 to 2018. The empirical results reveal the following: first, with the level of economic development as the threshold variable, there is a threshold effect in the impact of green technology innovation on the energy TFP; second, green technology innovation has an impact on the energy TFP through industrial structure upgrading; that is, industrial structure has a mediating effect in the influence mechanism; and third, there is heterogeneity in the impact of green technology innovation on the energy TFP among different regions in China, and the threshold effect only exists in the western region, since the central and eastern regions have crossed a certain developmental stage.
Predator-Induced Plasticity on Warning Signal and Larval Life-History Traits of the Aposematic Wood Tiger Moth, Arctia plantaginis
Authors: Almeida Diana Abondano , Mappes Johanna , Gordon Swanne
Published: June 2021

Predator-induced plasticity in life-history and antipredator traits during the larval period has been extensively studied in organisms with complex life-histories. However, it is unclear whether different levels of predation could induce warning signals in aposematic organisms. Here, we investigated whether predator-simulated handling affects warning coloration and life-history traits in the aposematic wood tiger moth larva, Arctia plantaginis. As juveniles, a larger orange patch on an otherwise black body signifies a more efficient warning signal against predators but this comes at the costs of conspicuousness and thermoregulation. Given this, one would expect that an increase in predation risk would induce flexible expression of the orange patch. Prior research in this system points to plastic effects being important as a response to environmental changes for life history traits, but we had yet to assess whether this was the case for predation risk, a key driver of this species evolution. Using a full-sib rearing design, in which individuals were reared in the presence and absence of a non-lethal simulated bird attack, we evaluated flexible responses of warning signal size (number of orange segments), growth, molting events, and development time in wood tiger moths. All measured traits except development time showed a significant response to predation. Larvae from the predation treatment developed a more melanized warning signal (smaller orange patch), reached a smaller body size, and molted more often. Our results suggest plasticity is indeed important in aposematic organisms, but in this case may be complicated by the trade-off between costly pigmentation and other life-history traits.
Generality and Shifts in Leaf Trait Relationships Between Alpine Aquatic and Terrestrial Herbaceous Plants on the Tibetan Plateau
Authors: Yang Lei , Zhao Haocun , Zuo Zhenjun , Li Xiangyan , Yu Dan , Wang Zhong
Published: June 2021

Plant traits mirror both evolutionary and environmental filtering process with universal trait-trait relationships across plant groups. However, plants also develop unique traits precisely to different habitats, inducing deviations of the trait coupling relations. In this study, we aimed to compare the differences in leaf traits and examine the generality and shifts of trait-trait relationships between alpine aquatic and terrestrial herbaceous plants on the Tibetan Plateau, to explore the precise adaptive strategies of aquatic and terrestrial plants for its habitats. We measured mass-based and area-based leaf N and P concentrations, N:P ratios and specific leaf area (SLA) of aquatic and terrestrial herbaceous plants. Standardized major axis analysis were applied to build the correlations for every trait pairs of each plant group, and then to compare the differences in the trait-trait correlations among different plant groups. Leaf Nmass and Pmass of two groups of aquatic plants (emergent and submerged plants) were higher, but N:P ratios were lower than those of two groups of terrestrial plants (sedges and grasses). Submerged plants had extremely high SLA, while grasses had the lowest SLA. Nmass positively correlated with Pmass in three out of four plant groups. The two terrestrial plant groups had positive Nmass-SLA relationships but these two traits coupled weakly in aquatic plants. Pmass showed positive relationships to SLA in three out of four plant groups. Significant shifts of trait-trait relationships between aquatic and terrestrial plants were observed. In general, aquatic plants, especially submerged plants, are characterized by higher SLA, greater leaf nutrientmass than terrestrial plants, tend to pursue fast-return investment strategies, and represent the acquisitive end of leaf economics spectrum. The deviations of trait-trait relationships between different plant groups reveal the precise adaptions of submerged plants to the unique aquatic habitats.
Chloroquine and Sulfadoxine–Pyrimethamine Resistance in Sub-Saharan Africa—A Review
Authors: Roux Alexandra T. , Maharaj Leah , Oyegoke Olukunle , Akoniyon Oluwasegun P. , Adeleke Matthew Adekunle , Maharaj Rajendra , Okpeku Moses
Published: June 2021

Malaria is a great concern for global health and accounts for a large amount of morbidity and mortality, particularly in Africa, with sub-Saharan Africa carrying the greatest burden of the disease. Malaria control tools such as insecticide-treated bed nets, indoor residual spraying, and antimalarial drugs have been relatively successful in reducing the burden of malaria; however, sub-Saharan African countries encounter great challenges, the greatest being antimalarial drug resistance. Chloroquine (CQ) was the first-line drug in the 20th century until it was replaced by sulfadoxine–pyrimethamine (SP) as a consequence of resistance. The extensive use of these antimalarials intensified the spread of resistance throughout sub-Saharan Africa, thus resulting in a loss of efficacy for the treatment of malaria. SP was replaced by artemisinin-based combination therapy (ACT) after the emergence of resistance toward SP; however, the use of ACTs is now threatened by the emergence of resistant parasites. The decreased selective pressure on CQ and SP allowed for the reintroduction of sensitivity toward those antimalarials in regions of sub-Saharan Africa where they were not the primary drug for treatment. Therefore, the emergence and spread of antimalarial drug resistance should be tracked to prevent further spread of the resistant parasites, and the re-emergence of sensitivity should be monitored to detect the possible reappearance of sensitivity in sub-Saharan Africa.
Immune Dysregulation and the Increased Risk of Complications and Mortality Following Respiratory Tract Infections in Adults With Down Syndrome
Authors: Illouz Tomer , Biragyn Arya , Iulita Maria Florencia , Flores-Aguilar Lisi , Dierssen Mara , De Toma Ilario , Antonarakis Stylianos E. , Yu Eugene , Herault Yann , Potier Marie-Claude , Botté Alexandra , Roper Randall , Sredni Benjamin , London Jacqueline , Mobley William , Strydom Andre , Okun Eitan
Published: June 2021

The risk of severe outcomes following respiratory tract infections is significantly increased in individuals over 60 years, especially in those with chronic medical conditions, i.e., hypertension, diabetes, cardiovascular disease, dementia, chronic respiratory disease, and cancer. Down Syndrome (DS), the most prevalent intellectual disability, is caused by trisomy-21 in ~1:750 live births worldwide. Over the past few decades, a substantial body of evidence has accumulated, pointing at the occurrence of alterations, impairments, and subsequently dysfunction of the various components of the immune system in individuals with DS. This associates with increased vulnerability to respiratory tract infections in this population, such as the influenza virus, respiratory syncytial virus, SARS-CoV-2 (COVID-19), and bacterial pneumonias. To emphasize this link, here we comprehensively review the immunobiology of DS and its contribution to higher susceptibility to severe illness and mortality from respiratory tract infections.
Obesity Causes Abrupt Changes in the Testicular Microbiota and Sperm Motility of Zebrafish
Authors: Su Yufang , He Liting , Hu Zhiyong , Li Ying , Zhang Yuan , Fan Zunpan , Zhao Kai , Zhang Huiping , Liu Chunyan
Published: June 2021

Background

Obesity is a recognized risk factor for low fertility and is becoming increasingly prevalent in many countries around the world. Obesity changes intestinal microbiota composition, causes inflammation of various organs, and also reduces sperm quality. Several microorganisms are present in the testis. However, whether obesity affects the changes of testicular microbiota and whether these changes are related to reduced fertility in obese men remain to be elucidated.

Methods

In the present study, a zebrafish obesity model was established by feeding with egg yolk powder. Sperm motility was measured by the Computer Assisted Sperm Analysis system, testicular microbial communities was assessed via 16s RNA sequencing, the immune response in zebrafish testis was quantified by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay, and the testicular tissue structure was detected by electron microscopy and hematoxylin–eosin staining.

Results

Compared with the control group, zebrafish sperm motility was dramatically reduced, the expression of testicular proinflammatory cytokines in the testes was upregulated, and the blood–testis barrier structure was disrupted in the obese group. In addition, testicular microbiome composition was clearly altered in the obese group.

Conclusion

Obesity alters testicular microbiota composition, and the reason behind the decreased sperm motility in obese zebrafish may be related to changes in the testicular microbial communities.
Monocyte and Macrophage miRNA: Potent Biomarker and Target for Host-Directed Therapy for Tuberculosis
Authors: Sampath Pavithra , Periyasamy Krisna Moorthi , Ranganathan Uma Devi , Bethunaickan Ramalingam
Published: June 2021

The end TB strategy reinforces the essentiality of readily accessible biomarkers for early tuberculosis diagnosis. Exploration of microRNA (miRNA) and pathway analysis opens an avenue for the discovery of possible therapeutic targets. miRNA is a small, non-coding oligonucleotide characterized by the mechanism of gene regulation, transcription, and immunomodulation. Studies on miRNA define their importance as an immune marker for active disease progression and as an immunomodulator for innate mechanisms, such as apoptosis and autophagy. Monocyte research is highly advancing toward TB pathogenesis and biomarker efficiency because of its innate and adaptive response connectivity. The combination of monocytes/macrophages and their relative miRNA expression furnish newer insight on the unresolved mechanism for Mycobacterium survival, exploitation of host defense, latent infection, and disease resistance. This review deals with miRNA from monocytes, their relative expression in different disease stages of TB, multiple gene regulating mechanisms in shaping immunity against tuberculosis, and their functionality as biomarker and host-mediated therapeutics. Future collaborative efforts involving multidisciplinary approach in various ethnic population with multiple factors (age, gender, mycobacterial strain, disease stage, other chronic lung infections, and inflammatory disease criteria) on these short miRNAs from body fluids and cells could predict the valuable miRNA biosignature network as a potent tool for biomarkers and host-directed therapy.
Epidemiology of Pregnancy Complications Through the Lens of Immunological Memory
Authors: Gregory Emily J. , Liu James , Miller-Handley Hilary , Kinder Jeremy M. , Way Sing Sing
Published: June 2021

In the fifteen minutes it takes to read this short commentary, more than 400 babies will have been born too early, another 300 expecting mothers will develop preeclampsia, and 75 unborn third trimester fetuses will have died in utero (stillbirth). Given the lack of meaningful progress in understanding the physiological changes that occur to allow a healthy, full term pregnancy, it is perhaps not surprising that effective therapies against these great obstetrical syndromes that include prematurity, preeclampsia, and stillbirth remain elusive. Meanwhile, pregnancy complications remain the leading cause of infant and childhood mortality under age five. Does it have to be this way? What more can we collectively, as a biomedical community, or individually, as clinicians who care for women and newborn babies at high risk for pregnancy complications, do to protect individuals in these extremely vulnerable developmental windows? The problem of pregnancy complications and neonatal mortality is extraordinarily complex, with multiple unique, but complementary perspectives from scientific, epidemiological and public health viewpoints. Herein, we discuss the epidemiology of pregnancy complications, focusing on how the outcome of prior pregnancy impacts the risk of complication in the next pregnancy — and how the fundamental immunological principle of memory may promote this adaptive response.
Aspirin Actions in Treatment of NSAID-Exacerbated Respiratory Disease
Authors: Sehanobish Esha , Asad Mohammad , Barbi Mali , Porcelli Steven A. , Jerschow Elina
Published: June 2021

Non-steroidal Anti-inflammatory drugs (NSAID)-exacerbated respiratory disease (N-ERD) is characterized by nasal polyposis, chronic rhinosinusitis, adult-onset asthma and hypersensitive reactions to cyclooxygenase-1 (COX-1) inhibitors. Among the available treatments for this disease, a combination of endoscopic sinus surgery followed by aspirin desensitization and aspirin maintenance therapy has been an effective approach. Studies have shown that long-term aspirin maintenance therapy can reduce the rate of nasal polyp recurrence in patients with N-ERD. However, the exact mechanism by which aspirin can both trigger and suppress airway disease in N-ERD remains poorly understood. In this review, we summarize current knowledge of aspirin effects in N-ERD, cardiovascular disease, and cancer, and consider potential mechanistic pathways accounting for the effects of aspirin in N-ERD.
St Helena Marine Water Quality: Background Conditions and Development of Assessment Levels for Coastal Pollutants
Authors: Painting Suzanne Jane , Haigh Eleanor K. , Graham Jennifer A. , Morley Simon A. , Henry Leeann , Clingham Elizabeth , Hobbs Rhys , Mynott Frances , Bersuder Philippe , Walker David I. , Stamford Tammy
Published: June 2021

St Helena is an isolated oceanic island located in the tropical South Atlantic, and knowledge of broadscale oceanography and productivity in its surrounding waters is limited. This study used model outputs (2007-2017), remote sensing data (1998-2017) and survey measurements (April 2018 and 2019) to determine background conditions for nutrients, chlorophyll and suspended particulate matter (SPM) in offshore waters and propose standards (thresholds) for assessing inshore water quality based on 50% deviation from seasonal (usually June to November) or annual averages. Seasonal thresholds were proposed for surface nitrate (average 0.18 μM), phosphate (average 0.26 μM), silicate (average 2.60 μM), chlorophyll (average 0.45 μg chl l–1), and SPM (average 0.96 mg l–1). Associated background values for most surface parameters (phosphate 0.17 μM, silicate 1.57 μM, chlorophyll 0.30 μg chl l–1; from model outputs and remote sensing) were slightly higher than offshore observations (April 2019). For nitrate, the average background value (0.12 μM) was lower than the observed average (0.24 μM). At depth (150-500 m), annual background values from model outputs were high (nitrate 26.8 μM, phosphate 1.8 μM, silicate 17.3 μM). Observed water masses at depths >150 m, identified to be of Antarctic and Atlantic origin, were nutrient-rich (e.g., 16 μM for nitrate, April 2019) and oxygen deficient (<4-6 mg l–1). A thermocline layer (betweenca.10 and 230 m), characterized by a sub-surface chlorophyll maximum (average 0.3-0.5 μg chl l–1) near the bottom of the euphotic zone (ca.100 m), is likely to sustain primary and secondary production at St Helena. For assessing inshore levels of chemical contaminants and fecal bacteria estimated from survey measurements, standards were derived from the literature. A preliminary assessment of inshore observations using proposed thresholds from surface offshore waters and relevant literature standards indicated concerns regarding levels of nutrients and fecal bacteria at some locations. More detailed modeling and/or field-based studies are required to investigate seasonal trends and nutrient availability to inshore primary producers and to establish accurate levels of any contaminants of interest or risk to the marine environment.
Dissolved and Particulate Beryllium Isotopes in the Pearl River Estuary: Their Geochemical Behavior in Estuarine Water and Potential Contributions From Anthropogenic Sources
Authors: Kong Weiyuan , Zhou Liping , Aumaître Georges , Bourlès Didier , Keddadouche Karim
Published: June 2021

The ratio of cosmogenic 10Be and its stable isotope 9Be has been used as a proxy of long-term continental weathering fluxes and denudation rates, but transport processes of these isotopes from river water to estuarine water and seawater, as well as interference of potential anthropogenic source of 9Be on natural 10Be/9Be around populated estuaries are not well constrained. Here, we present results of 10Be and 9Be concentrations of dissolved and reactive particulate phase in the Pearl River Estuary (PRE) and its eight major outlets. The concentrations of Cu, Cd, and Pb are also measured, allowing us to assess their contamination levels and anthropogenic source together with 9Be by the geo-accumulation index (Igeo–reac) and enrichment factor (EF). A wide distribution pattern of dissolved 10Be (137–1,194 at/gwater) and 9Be (0.781–8.31 × 10–12 g/gwater) among these outlets is observed. The distribution coefficients (Kd) of both isotopes between sediment and water are in the order of 105, and on average only 5% of 10Be exists as dissolved form. Compared with total meteoric 10Be deposited on the river basin, 23% of the meteoric 10Be is retained while 38% of 10Be finally escape the estuary and is transported into coastal seawater. Despite the high contamination levels of Cu and Cd, the lower Igeo–reac and EF values of 9Be indicate that 9Be is hardly polluted by anthropogenic source. Thus, the 10Be/9Be in the PRE area is mainly associated with natural processes instead of human activities.
Are Steroids Still Useful in Immunosuppressed Patients With Inflammatory Bowel Disease? A Retrospective, Population-Based Study
Authors: Sicilia Beatriz , Arias Lara , Hontoria Gadea , García Nieves , Badia Ester , Gomollón Fernando
Published: June 2021

Background: Effectiveness of corticosteroids in immunosuppressed patients with inflammatory bowel disease (IBD) has not been completely elucidated.

Aims: To assess the effectiveness and examine the long-term follow-up of systemic or low-bioavailability oral steroid treatment for moderate flare-ups in patients treated with immunosuppressive drugs.

Methods: Immunosuppressed patients with inflammatory bowel disease (IBD) from our population-data registry were analyzed. For statistical analysis, the chi-square test, Mann-Whitney U test, and Kaplan-Meier survival analysis were used as appropriate.

Results: A total of 392 patients with IBD and a median of 82 (range, 6–271) months of immunosuppressive (IMM) treatment were identified. The mean follow-up was 87 months (range, 6–239 months). A total of 89 patients (23%) needed at least one steroid course during their follow-up. Average time from IMM to steroid treatment was 26 (range, 6–207) months. In patients with CD, fibrostenotic (B2) and fistulizing (B3) behaviors [p = 0.005; odds ratio (OR): 2.284] were risk factors for using steroids after IMM treatment. In patients with UC, no statistically significant variables were identified. Of the 89 patients who received one first steroid course, 49 (55%) stepped up to biological treatment or surgery after a median of 13 months (range, 0–178), 19 (21%) were treated with repeated steroid courses, and 31 (35%) required no further treatment. Patients with CD had a higher risk (p = 0.007; OR: 3.529) of receiving biological treatment or surgery than patients with UC. The longer the patients with UC (more months) spent using steroids, the greater the risk of requiring treatment with biological drugs or surgery (p = 0.009).

Conclusion: A total of 23% of the immunosuppressed patients with IBD received at least one course of steroid treatment. In patients under immunosuppression treated with at least a course of steroids, CD patients were more likely stepped up to biologics and/or surgery than UC patients. In patients with CD, B2/B3 behavior pattern were significant risk factors. After one course of steroids only 35% of immunosuppressed IBD patients remained in remission without needing treatment scalation.
Optimizing Diet to Slow CKD Progression
Authors: Molina Pablo , Gavela Eva , Vizcaíno Belén , Huarte Emma , Carrero Juan Jesús
Published: June 2021

Due to the unique role of the kidney in the metabolism of nutrients, patients with chronic kidney disease (CKD) lose the ability to excrete solutes and maintain homeostasis. Nutrient intake modifications and monitoring of nutritional status in this population becomes critical, since it can affect important health outcomes, including progression to kidney failure, quality of life, morbidity, and mortality. Although there are multiple hemodynamic and metabolic factors involved in the progression and prognosis of CKD, nutritional interventions are a central component of the care of patients with non-dialysis CKD (ND-CKD) and of the prevention of overweight and possible protein energy-wasting. Here, we review the reno-protective effects of diet in adults with ND-CKD stages 3–5, including transplant patients.
Comparison of Residual Pulmonary Abnormalities 3 Months After Discharge in Patients Who Recovered From COVID-19 of Different Severity
Authors: Zhou Mei , Xu Juanjuan , Liao Tingting , Yin Zhengrong , Yang Fan , Wang Kai , Wang Zhen , Yang Dan , Wang Sufei , Peng Yi , Peng Shuyi , Wu Feihong , Chen Leqing , Jin Yang
Published: June 2021

Background and Objectives: To investigate whether coronavirus disease 2019 (COVID-19) survivors who had different disease severities have different levels of pulmonary sequelae at 3 months post-discharge.

Methods: COVID-19 patients discharged from four hospitals 3 months previously, recovered asymptomatic patients from an isolation hotel, and uninfected healthy controls (HCs) from the community were prospectively recruited. Participants were recruited at Wuhan Union Hospital and underwent examinations, including quality-of-life evaluation (St. George Respiratory Questionnaire [SGRQ]), laboratory examination, chest computed tomography (CT) imaging, and pulmonary function tests.

Results: A total of 216 participants were recruited, including 95 patients who had recovered from severe/critical COVID-19 (SPs), 51 who had recovered from mild/moderate disease (MPs), 28 who had recovered from asymptomatic disease (APs), and 42 HCs. In total, 154 out of 174 (88.5%) recovered COVID-19 patients tested positive for serum SARS-COV-2 IgG, but only 19 (10.9%) were still positive for IgM. The SGRQ scores were highest in the SPs, while APs had slightly higher SGRQ scores than those of HCs; 85.1% of SPs and 68.0% of MPs still had residual CT abnormalities, mainly ground-glass opacity (GGO) followed by strip-like fibrosis at 3 months after discharge, but the pneumonic lesions were largely absorbed in the recovered SPs or MPs relative to findings in the acute phase. Pulmonary function showed that the frequency of lung diffusion capacity for carbon monoxide abnormalities were comparable in SPs and MPs (47.1 vs. 41.7%), while abnormal total lung capacity (TLC) and residual volume (RV) were more frequent in SPs than in MPs (TLC, 18.8 vs. 8.3%; RV, 11.8 vs. 0%).

Conclusions: Pulmonary abnormalities remained after recovery from COVID-19 and were more frequent and conspicuous in SPs at 3 months after discharge.