bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding and Managing Harmful Algal Bloom Risks in a Changing Climate: Lessons From the European CoCliME Project
Authors: West Jennifer Joy , Järnberg Linn , Berdalet Elisa , Cusack Caroline
Published: May 2021

This paper discusses the conceptual and methodological challenges to co-developing high-quality and transferable knowledge to understand and manage harmful algal bloom (HAB) risks as part of adaptation to changing aquatic ecosystems in Europe. Global HAB-climate change research efforts to date have focused on enhancing the credibility of scientific knowledge by conducting basic scientific research aimed at understanding the physical and biogeochemical drivers and mechanisms shaping HAB dynamics in order to predict their occurrence and prevent their societal and ecological impacts. However, the rapid and interconnected changes occurring in marine ecosystems worldwide necessitate a simultaneous shift toward enhancing the salience, legitimacy, usefulness, and usability of this knowledge for decision-making. To address this need, we present and discuss empirical findings from the marine-focused CoCliME project, which set out to co-develop user-oriented climate services to support HAB risk mitigation and adaptation in European coastal regions. We present lessons learned in relation to four areas of project implementation, across five regional cases, that emerged as essential for enhancing the quality of knowledge for managing HAB-climate risks: (1) Engaging stakeholders to understand their knowledge, experiences, interests and concerns; (2) Co-developing a shared terminology and framing of the “HAB-related problems”; (3) Advancing scientific understanding of drivers and interactions shaping HAB-climate risks and; (4) Co-producing prototype services that integrate social and HAB-climate data and knowledge to support decision-making. We find that efforts to reduce scientific knowledge gaps and uncertainties about HAB-climate linkages (efforts to enhance credibility), while important, risk overlooking key aspects of knowledge co-production and application that are necessary to render this knowledge more salient, legitimate, useful, and usable. Understanding the multi-risk decision-making context within which societal stakeholders appraise HAB and climate change risks and approaching knowledge co-production as a learning process, are vital lessons learned in this respect. Drawing on project learning, we highlight key priorities for enhancing the societal relevance and impact of HABs-climate research during the UN Decade of Ocean Science for Sustainable Development.
Egophoricity and Perspective: A View From Spoken Swedish
Authors: Bergqvist Henrik
Published: May 2021

From the point of view of everyday talk and especially, casual conversation, it is obvious that language use is highly perspectivized with a clear focus on the speech-act participants. This fact is supported by observations regarding the pervasiveness of egophoric pronouns and the frequent use of the modal particlesjuandvälin spoken Swedish. The paper demonstrates how egophoric pronouns, modal particles, and mental verbs are used to signal the epistemic perspective of the speech-act participants, i.e., when the knowledge and attention of the speech-act participants are at stake. These formally distinct resources show patterns of co-distribution that permit an analysis of forms in terms of how they signal shared/private access to events from the perspective of the speaker and the addressee.
Communicating Corrected Risk Assessments and Uncertainty About COVID-19 in the Post-truth Era
Authors: Fernandes Adalberto
Published: May 2021

The COVID-19 pandemic has been a challenge for science communication in terms of addressing the question of uncertainty and how it translates into risk. This task has been aggravated by the complexity of the pandemic and the current post-truth environment. The article suggests that there is a need to analyze the practices of correcting risk information that is uncertain, but not necessarily false, made by online news media about COVID-19. This is a point of analysis where the uncertainty and risk linked to science, the pandemic, and the post-truth condition meet. The qualitative discursive analysis yielded three important results: (1) uncertainty can be fought by increasing uncertainty; (2) a multiplication of facts or reasons may not be the most prominent strategy in practices of correction; and (3) the use of hyperlinks with additional information can increase uncertainty and risk.
Finding Satisfaction in Belonging: Preservice Teacher Subjective Well-Being and its Relationship to Belonging, Trust, and Self-Efficacy
Authors: Bjorklund Jr. Peter , Warstadt Melissa F. , Daly Alan J.
Published: May 2021

The well-being of teachers and preservice teachers has been a topic extensively explored through the lens of burnout and stress. Despite its manifold benefits, few studies have explored PST well-being through the lens of subjective well-being. Grounding our study in positive psychology, we explore the relationships between preservice teachers’ subjective well-being, program sense of belonging, relational trust, and self-efficacy. Our participants included 63 multiple- and single-subject preservice teachers in a major university teacher education program in the western United States. They were surveyed in May 2019 in the final month of completing their program. We found that sense of belonging, relational trust, and self-efficacy individually are positively associated with well-being. A mediation analysis revealed that the relationship between relational trust and subjective well-being is mediated by program sense of belonging, which may indicate the importance of cohesion in a cohort-based teacher education program.
Improvement of Condensation Model With the Presence of Non-Condensable Gas for Thermal-Hydraulic Analysis in Containment
Authors: Wang Tianlin , Wang Di , Tong Lili , Cao Xuewu
Published: May 2021

Steam condensation plays a key role in prediction of the pressure behavior and hydrogen distribution in the containment during a hypothetical loss-of-coolant accident or a severe accident in a light water nuclear reactor. The objective of this study is to evaluate and improve the condensation model in GASFLOW code. Reynolds analogy coupled with wall function and Chilton-Colburn empirical analogy is used to model heat and mass transfer in GASFLOW, which has requirements for dimensional distance of the first cell near the wall and some deficiencies in description of heat and mass transfer process in the stagnant zone. Based on the evaluation of original condensation, the results shows good agreement with COPAIN experiment cases where the mass fraction of air ranges from 76.7 to 86.4%. However, with the changes in geometry of the facility and the presence of helium, the original model has a large deviation in the prediction of pressure, temperature and gas distribution compared with MISTRA ISP47 (OECD International Standard Problem No. 47) experiment data. This work proposes a modified condensation model which uses McAdams correlation and Schlichting correlation with a weight factor to calculate natural, forced, or mixed convection heat transfer coefficient, and adopts Chilton-Colburn empirical analogy to model mass transfer. The modified model has no requirement for the dimensionless distance near the wall in heat and mass transfer calculation and improves the prediction performance of heat transfer in stagnant zone. The prediction result of the modified model shows good agreements with MISTRA ISP47 problem, and the error of it compared with COPAIN experiment data is within 25% which is the same as that predicted by the original model.
Impacts of Infrastructure Developments on Ecosystem Services Potential in Istanbul
Authors: Menteşe Emin Yahya , Tezer Azime
Published: May 2021

Istanbul has been subject to drastic spatial changes in the last decade due to major investments in the northern section of the city. The primary purpose of the research was to interpret the ecological outcomes of spatial use changes due to such urban development activities and enhance the environmental impact assessment process by adopting an analytical and holistic approach. The approach used in the analysis is based on a model called “matrix model” developed specifically to estimate ecosystem services (ES) capacity of a given area depending on the spatial use types. With the use of this method, one can estimate how spatial use influences ES capacity in positive or negative ways, which ES type is affected most, and which part of the spatial change causes most impact on ecological assets. The methodology is applied for three different investment projects in Istanbul, respectively: North Marmara Motorway (NMM), Istanbul Airport, and Canal Istanbul. While the first two have been mostly completed, the third is in the planning phase. Corine Land Cover datasets for 2012 and 2018 are used as basis datasets within the methodology, and spatial plans of Canal Istanbul are used for future projections. Based on these datasets, ES capacity analysis is carried out for each year for the area of investment, and estimation results are compared. The analysis results indicate that these investments have caused and will cause severe ES losses as expected. The outputs prove that the “matrix model” can be used to evaluate ecological impacts in a straightforward, efficient, and inclusive way for evaluating spatial changes. The authors suggest that environmental impact assessments for such major investments must represent a comprehensive outlook based on more simplistic but yet informative approaches that highlight the potential losses of not only ecological assets but also their functions and benefits. In this context, it is strongly recommended that there is a paradigm shift in the understanding of the “environmental impact” in a direction where environment is not acted upon as a solid, rigid, and stable “land cover” but instead a living organism that produces benefits and services for the whole components of the ecosystem on earth, including humankind.
A Parasite’s Paradise: Biotrophic Species Prevail Oomycete Community Composition in Tree Canopies
Authors: Jauss Robin-Tobias , Walden Susanne , Fiore-Donno Anna Maria , Schaffer Stefan , Wolf Ronny , Feng Kai , Bonkowski Michael , Schlegel Martin
Published: May 2021

Oomycetes (Stramenopiles, protists) are among the most severe plant pathogens, comprising species with a high economic and ecologic impact on forest ecosystems. Their diversity and community structures are well studied in terrestrial habitats, but tree canopies as huge and diverse habitats have been widely neglected. A recent study highlighted distinct oomycete communities in the canopy stratum compared to the ground region of three temperate deciduous trees (Quercus robur, Tilia cordata, Fraxinus excelsior). While the communities from the two strata were distinct when taking oomycete abundances into account, they were rather similar when only OTU presence/absence was considered. It remains, however, unknown if this homogeneity in the OTU presence also leads to a functional homogenisation among microhabitats within the two strata ground and canopy. In this study, we supplemented functional traits to oomycete communities in the tree microhabitats, which were determined over a time period of 2 years with a metabarcoding approach. Our results showed that even though most oomycetes occurred in all microhabitats, a strong discrepancy between the strata and correspondingly the distribution of oomycete lifestyles could be observed. This pattern was constant over several seasons. Obligate biotrophic species, exclusively feeding on living host tissue, dominated the canopy region, implying tree canopies to be a hitherto neglected reservoir for parasitic protists. OTUs assigned to the genus Hyaloperonospora—parasites highly specialised on hosts that were not sampled—could be determined in high abundances in the canopy and the surrounding air, challenging the strict host dependencies ruled for some oomycetes. Our findings further contribute to the understanding of oomycete ecosystem functioning in forest ecosystems.
“Now You Have Become Doctors”: Lady Health Workers' Experiences Implementing an mHealth Application in Rural Pakistan
Authors: Kinshella Mai-Lei Woo , Sheikh Sana , Bawani Sohail , La Michelle , Sharma Sumedha , Vidler Marianne , Magee Laura A. , Dadelszen Peter von , Bhutta Zulfiqar , Qureshi Rahat Najam , Payne Beth A. ,   The CLIP Working Group
Published: May 2021

Background: PIERS on the Move (POM) is a mobile health application developed to support community health workers identification and management of women at risk of adverse outcomes from pre-eclampsia. The objective of this study was to evaluate the impact of using POM in Pakistan on Lady Health Workers' (LHWs) knowledge and self-efficacy related to caring for women with pre-eclampsia, and their perception of usefulness of the tool.

Methodology: An evaluation was designed for health care workers involved in the Community-Level Intervention for Pre-eclampsia (CLIP) cluster randomized trial from 2014 to 2016 in Sindh Province, Pakistan (NCT01911494). A semi-structured focus group guide was developed based on the Technology Acceptance Model (TAM), which theorizes that an individual's behavioral intention to use a system is determined by perceived usefulness and ease of use. Preliminary qualitative analysis was undertaken by the Pakistan and Canadian teams to create a coding framework for full qualitative analysis, which was completed using NVivo12.

Results: Three key informant interviews were conducted with two Lady Health Supervisors and one Senior Medical Officer. Sixty-two LHWs were included in three focus group discussions. LHWs found the POM app easy to use and useful for their work as a helpful repository for maternal health information and guiding counseling and management of pre-eclampsia. LHWs reported increased knowledge and confidence in their work. Availability of clinical homecare, including postpartum, was felt to positively impact healthcare provided to pregnant and postpartum women. Potential community level impacts included strengthening relationships between health care providers and communities and between LHWs and the health system. LHWs shared reports of earlier care-seeking and increased awareness of maternal health issues by community members.

Conclusions: LHWs carry a large burden of responsibility for community health in rural Pakistan and appreciated the investment in their skills and capacity during the CLIP trial with the POM app. Investing in communications technology for community health workers through improved referrals and follow up may strengthen cohesiveness of the health system overall.
Chemokines in Prediabetes and Type 2 Diabetes: A Meta-Analysis
Authors: Pan Xiongfeng , Kaminga Atipatsa C. , Wen Shi Wu , Liu Aizhong
Published: May 2021

Background

A growing number of studies found inconsistent results on the role of chemokines in the progression of type 2 diabetes (T2DM) and prediabetes (PDM). The purpose of this meta-analysis was to summarize the results of previous studies on the association between the chemokines system and T2DM/PDM.

Methods

We searched in the databases, PubMed, Web of Science, Embase and Cochrane Library, for eligible studies published not later than March 1, 2020. Data extraction was performed independently by 2 reviewers, on a standardized, prepiloted form. Group differences in chemokines concentrations were summarized using the standardized mean difference (SMD) with a 95% confidence interval (CI), calculated by performing a meta-analysis using the random-effects model.

Results

We identified 98 relevant studies that investigated the association between 32 different chemokines and T2DM/PDM. Altogether, these studies involved 14,708 patients and 14,574 controls. Results showed that the concentrations of CCL1, CCL2, CCL4, CCL5, CCL11, CXCL8, CXCL10 and CX3CL1 in the T2DM patients were significantly higher than that in the controls, while no difference in these concentrations was found between the PDM patients and controls.

Conclusion

Progression of T2DM may be associated with elevated concentrations of chemokines.

Meta-Analysis Registration

PROSPERO, identifier CRD42019148305.
The Impact of Dietary Sphingolipids on Intestinal Microbiota and Gastrointestinal Immune Homeostasis
Authors: Rohrhofer Johanna , Zwirzitz Benjamin , Selberherr Evelyne , Untersmayr Eva
Published: May 2021

The large surfaces of gastrointestinal (GI) organs are well adapted to their diverse tasks of selective nutritional uptake and defense against the external environment. To maintain a functional balance, a vast number of immune cells is located within the mucosa. A strictly regulated immune response is required to impede constant inflammation and to maintain barrier function. An increasing prevalence of GI diseases has been reported in Western societies over the past decades. This surge in GI disorders has been linked to dietary changes followed by an imbalance of the gut microbiome, leading to a chronic, low grade inflammation of the gut epithelium. To counteract the increasing health care costs associated with diseases, it is paramount to understand the mechanisms driving immuno-nutrition, the associations between nutritional compounds, the commensal gut microbiota, and the host immune response. Dietary compounds such as lipids, play a central role in GI barrier function. Bioactive sphingolipids (SLs), e.g. sphingomyelin (SM), sphingosine (Sph), ceramide (Cer), sphingosine-1- phosphate (S1P) and ceramide-1-phosphate (C1P) may derive from dietary SLs ingested through the diet. They are not only integral components of cell membranes, they additionally modulate cell trafficking and are precursors for mediators and second messenger molecules. By regulating intracellular calcium levels, cell motility, cell proliferation and apoptosis, SL metabolites have been described to influence GI immune homeostasis positively and detrimentally. Furthermore, dietary SLs are suggested to induce a shift in the gut microbiota. Modes of action range from competing with the commensal bacteria for intestinal cell attachment to prevention from pathogen invasion by regulating innate and immediate defense mechanisms. SL metabolites can also be produced by gut microorganisms, directly impacting host metabolic pathways. This review aims to summarize recent findings on SL signaling and functional variations of dietary SLs. We highlight novel insights in SL homeostasis and SL impact on GI barrier function, which is directly linked to changes of the intestinal microbiota. Knowledge gaps in current literature will be discussed to address questions relevant for understanding the pivotal role of dietary SLs on chronic, low grade inflammation and to define a balanced and healthy diet for disease prevention and treatment.
dmLT Adjuvant Enhances Cytokine Responses to T Cell Stimuli, Whole Cell Vaccine Antigens and Lipopolysaccharide in Both Adults and Infants
Authors: Akhtar Marjahan , Nizam Nuder Nower , Basher Salima Raiyan , Hossain Lazina , Akter Sarmin , Bhuiyan Taufiqur Rahman , Qadri Firdausi , Lundgren Anna
Published: May 2021

Enhancement of mucosal immune responses in children and infants using novel adjuvants such as double mutant heat labile toxin (dmLT) is an important goal in the enteric vaccine field. dmLT has been shown to enhance mucosal IgA responses to the oral inactivated enterotoxigenic Escherichia coli (ETEC) vaccine ETVAX. dmLT can enhance IL-17A production from adult T cells, which may increase the production and secretion of mucosal IgA antibodies. However, the adjuvant mechanism remains to be fully elucidated and might differ between infants and adults due to age-related differences in the development of the immune system. The main objective of this study was to determine how dmLT influences antigen presenting cells and T cells from infants compared to adults, and the role of IL-1β for mediating the adjuvant activity. Peripheral blood mononuclear cells (PBMCs) from Bangladeshi infants (6-11 months) and adults (18-40 years) were stimulated with the mitogen phytohaemagglutinin (PHA), the superantigen Staphylococcal enterotoxin B (SEB), ETVAX whole cell component (WCC) or E. coli lipopolysaccharide (LPS) ± dmLT, and cytokine production was measured using ELISA and electrochemiluminescence assays. The adjuvant dmLT significantly enhanced SEB- and PHA-induced IL-17A, but not IFN-γ responses, in PBMCs from both infants and adults. Blocking experiments using an IL-1 receptor antagonist demonstrated the importance of IL-1 signaling for the adjuvant effect. dmLT, ETVAX WCC and LPS induced dose-dependent IL-1β responses of comparable magnitudes in infant and adult cells. Depletion experiments suggested that IL-1β was mainly produced by monocytes. dmLT enhanced IL-1β responses to low doses of WCC and LPS, and the adjuvant effect appeared over a wider dose-range of WCC in infants. dmLT and WCC also induced IL-6, IL-23 and IL-12p70 production in both age groups and dmLT tended to particularly enhance IL-23 responses to WCC. Our results show that dmLT can induce IL-1β as well as other cytokines, which in turn may enhance IL-17A and potentially modulate other immunological responses in both infants and adults. Thus, dmLT may have an important function in promoting immune responses to the ETVAX vaccine, as well as other whole cell- or LPS-based vaccines in infants in low- and middle-income countries.
Pulmonary Procoagulant and Innate Immune Responses in Critically Ill COVID-19 Patients
Authors: Nossent Esther J. , Schuurman Alex R. , Reijnders Tom D.Y. , Saris Anno , Jongerius Ilse , Blok Siebe G. , de Vries Heder , Duitman JanWillem , Vonk Noordegraaf Anton , Meijboom Lilian J. , Lutter René , Heunks Leo , Bogaard Harm Jan , van der Poll Tom
Published: May 2021

Rationale

Systemic activation of procoagulant and inflammatory mechanisms has been implicated in the pathogenesis of COVID-19. Knowledge of activation of these host response pathways in the lung compartment of COVID-19 patients is limited.

Objectives

To evaluate local and systemic activation of coagulation and interconnected inflammatory responses in critically ill COVID-19 patients with persistent acute respiratory distress syndrome.

Methods

Paired bronchoalveolar lavage fluid and plasma samples were obtained from 17 patients with COVID-19 related persistent acute respiratory distress syndrome (mechanical ventilation > 7 days) 1 and 2 weeks after start mechanical ventilation and compared with 8 healthy controls. Thirty-four host response biomarkers stratified into five functional domains (coagulation, complement system, cytokines, chemokines and growth factors) were measured.

Measurements and Main Results

In all patients, all functional domains were activated, especially in the bronchoalveolar compartment, with significantly increased levels of D-dimers, thrombin-antithrombin complexes, soluble tissue factor, C1-inhibitor antigen and activity levels, tissue type plasminogen activator, plasminogen activator inhibitor type I, soluble CD40 ligand and soluble P-selectin (coagulation), next to activation of C3bc and C4bc (complement) and multiple interrelated cytokines, chemokines and growth factors. In 10 patients in whom follow-up samples were obtained between 3 and 4 weeks after start mechanical ventilation many bronchoalveolar and plasma host response biomarkers had declined.

Conclusions

Critically ill, ventilated patients with COVID-19 show strong responses relating to coagulation, the complement system, cytokines, chemokines and growth factors in the bronchoalveolar compartment. These results suggest a local pulmonary rather than a systemic procoagulant and inflammatory “storm” in severe COVID-19.
Medicinal Plant Leaf Extract From Sage and Lemon Verbena Promotes Intestinal Immunity and Barrier Function in Gilthead Seabream (Sparus aurata)
Authors: Salomón Ricardo , Reyes-López Felipe E. , Tort Lluis , Firmino Joana P. , Sarasquete Carmen , Ortiz-Delgado Juan B. , Quintela José C. , Pinilla-Rosas José M. , Vallejos-Vidal Eva , Gisbert Enric
Published: May 2021

The inclusion of a medicinal plant leaf extract (MPLE) from sage (Salvia officinalis) and lemon verbena (Lippia citriodora), rich in verbascoside and triterpenic compounds like ursolic acid, was evaluated in gilthead seabream (Sparus aurata) fed a low fishmeal-based diet (48% crude protein, 17% crude fat, 21.7 MJ kg-1, 7% fishmeal, 15% fish oil) for 92 days. In particular, the study focused on the effect of these phytogenic compounds on the gut condition by analyzing the transcriptomic profiling (microarray analysis) and histological structure of the intestinal mucosa, as well as the histochemical properties of mucins stored in goblet cells. A total number of 506 differentially expressed genes (285 up- and 221 down-regulated) were found when comparing the transcriptomic profiling of the intestine from fish fed the control and MPLE diets. The gut transcripteractome revealed an expression profile that favored biological mechanisms associated to the 1) immune system, particularly involving T cell activation and differentiation, 2) gut integrity (i.e., adherens and tight junctions) and cellular proliferation, and 3) cellular proteolytic pathways. The histological analysis showed that the MPLE dietary supplementation promoted an increase in the number of intestinal goblet cells and modified the composition of mucins’ glycoproteins stored in goblet cells, with an increase in the staining intensity of neutral mucins, as well as in mucins rich in carboxylated and weakly sulfated glycoconjugates, particularly those rich in sialic acid residues. The integration of transcriptomic and histological results showed that the evaluated MPLE from sage and lemon verbena is responsible for the maintenance of intestinal health, supporting gut homeostasis and increasing the integrity of the intestinal epithelium, which suggests that this phytogenic may be considered as a promising sustainable functional additive for aquafeeds.
RDUR, a lncRNA, Promotes Innate Antiviral Responses and Provides Feedback Control of NF-κB Activation
Authors: Chen Yuhai , Hu Jiayue , Liu Shasha , Chen Biao , Xiao Meng , Li Yingying , Liao Yuan , Rai Kul Raj , Zhao Zhonghui , Ouyang Jing , Pan Qidong , Zhang Lianfeng , Huang Shile , Chen Ji-Long
Published: May 2021

Influenza A virus (IAV), a highly infectious respiratory pathogen, remains a major threat to global public health. Numerous long non-coding RNAs (lncRNAs) have been shown to be implicated in various cellular processes. Here, we identified a new lncRNA termed RIG-I-dependent IAV-upregulated noncoding RNA (RDUR), which was induced by infections with IAV and several other viruses. Both in vitro and in vivo studies revealed that robust expression of host RDUR induced by IAV was dependent on the RIG-I/NF-κB pathway. Overexpression of RDUR suppressed IAV replication and downregulation of RDUR promoted the virus replication. Deficiency of mouse RDUR increased virus production in lungs, body weight loss, acute organ damage and consequently reduced survival rates of mice, in response to IAV infection. RDUR impaired the viral replication by upregulating the expression of several vital antiviral molecules including interferons (IFNs) and interferon-stimulated genes (ISGs). Further study showed that RDUR interacted with ILF2 and ILF3 that were required for the efficient expression of some ISGs such as IFITM3 and MX1. On the other hand, we found that while NF-κB positively regulated the expression of RDUR, increased expression of RDUR, in turn, inactivated NF-κB through a negative feedback mechanism to suppress excessive inflammatory response to viral infection. Together, the results demonstrate that RDUR is an important lncRNA acting as a critical regulator of innate immunity against the viral infection.
A Review of the Various Roles and Participation Levels of B-Cells in Non-Infectious Uveitis
Authors: Zhu Lei , Chen Binyao , Su Wenru
Published: May 2021

Non-infectious uveitis is an inflammatory disorder of the eye that accounts for severe visual loss without evident infectious agents. While T cells are supposed to dominate the induction of inflammation in non-infectious uveitis, the role of B cells in the pathogenesis of this disease is obscure. Therefore, this review aimed to discuss diverse B-cell participation in different non-infectious uveitides and their roles in the pathogenesis of this disease as well as the mechanism of action of rituximab. Increasing evidence from experimental models and human non-infectious uveitis has suggested the participation of B cells in non-infectious uveitis. The participation levels vary in different uveitides. Furthermore, B cells play multiple roles in the pathogenic mechanisms. B cells produce autoantibodies, regulate T cell responses via antibody-independent functions, and constitute ectopic lymphoid structures. Regulatory B cells perform pivotal anti-inflammatory functions in non-infectious uveitis. Rituximab may work by depleting pro-inflammatory B cells and restoring the quantity and function of regulatory B cells in this disease. Identifying the levels of B-cell participation and the associated roles is beneficial for optimizing therapy. Diversified experimental model choices and emerging tools and/or methods are conducive for future studies on this topic.
Metabolic Fingerprinting Uncovers the Distinction Between the Phenotypes of Tuberculosis Associated COPD and Smoking-Induced COPD
Authors: Kim Da Jung , Oh Jee Youn , Rhee Chin Kook , Park Seoung Ju , Shim Jae Jeong , Cho Joo-Youn
Published: May 2021

Background: Although smoking is considered the main cause of chronic obstructive pulmonary disease (COPD), several other risk factors, including pulmonary tuberculosis (TB), contribute significantly to disease causation, particularly in developing countries. However, the underlying pathogenesis of TB-associated COPD (T-COPD) is unclear. Moreover, the need for prompt diagnosis and treatment of T-COPD to decrease the future burden of inflammation is underestimated. This study aimed to identify distinctive endogenous metabotypes of T-COPD, compared to smoking-associated COPD (S-COPD).

Methods: Cross-sectional metabolomic analyses and clinical examinations of serum samples were performed for three groups of 168 male subjects: T-COPD (n = 59), S-COPD (n = 70), and healthy normal controls (n = 39). To retain a broad spectrum of metabolites, we performed technically distinct analyses (global metabolomic profiling using LC-QTOFMS and targeted analyses using LC-MS/MS).

Results: Higher levels of IL-6 and C-reactive protein and St. George Respiratory Questionnaire scores were seen in the T-COPD group, compared to those in the S-COPD group. Global metabolomic profiling showed elevated metabolites, including arachidonic and eicosanoic acids, in the T-COPD group. Typical changes in tryptophan catabolism were observed through targeted profiling. Additionally, in the T-COPD group, kynurenine was elevated, and serotonin levels were reduced; therefore, indoleamine dioxygenase (IDO)/tryptophan hydroxylase (TPH) activities were dysregulated. Correlation analyses showed that changes in oxylipins were positively correlated with serum levels of IL-6 and C-reactive protein.

Conclusion: Patients with TB-related COPD have enhanced inflammatory responses that may be linked to fatty acid pathways and tryptophan catabolism, which could be novel therapeutic targets for T-COPD.
Inferring the Frank–Starling Curve From Simultaneous Venous and Arterial Doppler: Measurements From a Wireless, Wearable Ultrasound Patch
Authors: Kenny Jon-Émile S. , Barjaktarevic Igor , Mackenzie David C. , Rola Philippe , Haycock Korbin , Eibl Andrew M. , Eibl Joseph K.
Published: May 2021

The Frank–Starling relationship is a fundamental concept in cardiovascular physiology, relating change in cardiac filling to its output. Historically, this relationship has been measured by physiologists and clinicians using invasive monitoring tools, relating right atrial pressure (Pra) to stroke volume (SV) because the Pra-SV slope has therapeutic implications. For example, a critically ill patient with a flattened Pra-SV slope may have low Pra yet fail to increase SV following additional cardiac filling (e.g., intravenous fluids). Provocative maneuvers such as the passive leg raise (PLR) have been proposed to identify these “fluid non-responders”; however, simultaneously measuring cardiac filling and output via non-invasive methods like ultrasound is cumbersome during a PLR. In this Hypothesis and Theory submission, we suggest that a wearable Doppler ultrasound can infer the Pra-SV relationship by simultaneously capturing jugular venous and carotid arterial Doppler in real time. We propose that this method would confirm that low cardiac filling may associate with poor response to additional volume. Additionally, simultaneous assessment of venous filling and arterial output could help interpret and compare provocative maneuvers like the PLR because change in cardiac filling can be confirmed. If our hypothesis is confirmed with future investigation, wearable monitors capable of monitoring both variables of the Frank–Starling relation could be helpful in the ICU and other less acute patient settings.
Methanotrophs: Discoveries, Environmental Relevance, and a Perspective on Current and Future Applications
Authors: Guerrero-Cruz Simon , Vaksmaa Annika , Horn Marcus A. , Niemann Helge , Pijuan Maite , Ho Adrian
Published: May 2021

Methane is the final product of the anaerobic decomposition of organic matter. The conversion of organic matter to methane (methanogenesis) as a mechanism for energy conservation is exclusively attributed to the archaeal domain. Methane is oxidized by methanotrophic microorganisms using oxygen or alternative terminal electron acceptors. Aerobic methanotrophic bacteria belong to the phyla Proteobacteria and Verrucomicrobia, while anaerobic methane oxidation is also mediated by more recently discovered anaerobic methanotrophs with representatives in both the bacteria and the archaea domains. The anaerobic oxidation of methane is coupled to the reduction of nitrate, nitrite, iron, manganese, sulfate, and organic electron acceptors (e.g., humic substances) as terminal electron acceptors. This review highlights the relevance of methanotrophy in natural and anthropogenically influenced ecosystems, emphasizing the environmental conditions, distribution, function, co-existence, interactions, and the availability of electron acceptors that likely play a key role in regulating their function. A systematic overview of key aspects of ecology, physiology, metabolism, and genomics is crucial to understand the contribution of methanotrophs in the mitigation of methane efflux to the atmosphere. We give significance to the processes under microaerophilic and anaerobic conditions for both aerobic and anaerobic methane oxidizers. In the context of anthropogenically influenced ecosystems, we emphasize the current and potential future applications of methanotrophs from two different angles, namely methane mitigation in wastewater treatment through the application of anaerobic methanotrophs, and the biotechnological applications of aerobic methanotrophs in resource recovery from methane waste streams. Finally, we identify knowledge gaps that may lead to opportunities to harness further the biotechnological benefits of methanotrophs in methane mitigation and for the production of valuable bioproducts enabling a bio-based and circular economy.
Investigating the Relationships Between Three Important Functional Tasks Early After Stroke: Movement Characteristics of Sit-To-Stand, Sit-To-Walk, and Walking
Authors: Chandler Elizabeth Ann , Stone Thomas , Pomeroy Valerie Moyra , Clark Allan Brian , Kerr Andrew , Rowe Phillip , Ugbolue Ukadike Chris , Smith Jessica , Hancock Nicola Joanne
Published: May 2021

Background: Walking, sit-to-stand (STS) and sit-to-walk (STW) are all considered important functional tasks in achieving independence after stroke. Despite knowledge that sensitive measurement of movement patterns is crucial to understanding neuromuscular restitution, there is surprisingly little information available about the detailed biomechanical characteristics of, and relationships between, walking, sit-to-stand and sit-to-walk, particularly in the important time window early after stroke. Hence, here, the study aimed to:

Identify the biomechanical characteristics of and determine any differences in both movement fluidity (hesitation, coordination and smoothness) and duration of movement phases, between sit-to-stand (STS) and sit-to-walk (STW) in people early after stroke.

Determine whether measures of movement fluidity (hesitation, coordination, and smoothness) and movement phases during sit-to-stand (STS) and/or sit-to-walk (STW) are correlated strongly to commonly used measures of walking speed and/or step length ratio in people early after stroke.

Methods: This study consisted of secondary data analysis from the SWIFT Cast Trial. Specifically, we investigated movement fluidity using established assessments of smoothness, hesitation and coordination and the time duration for specific movement phases in a group of 48 people after stroke. Comparisons were made between STS and STW and relationships to walking measures were explored.

Results: Participants spent significantly more time in the initial movement phase, flexion momentum, during STS [mean time (SD) 1.74 ±1.45 s] than they did during STW [mean time (SD) 1.13 ± 1.03 s]. STS was also completed more smoothly but with more hesitation and greater coordination than the task of STW. No strong relationships were found between movement fluidity or duration with walking speed or step length symmetry.

Conclusions: Assessment of movement after stroke requires a range of functional tasks and no one task should predominate over another. Seemingly similar or overlapping tasks such as STS and STW create distinct biomechanical characteristics which can be identified using sensitive, objective measures of fluidity and movement phases but there are no strong relationships between the functional tasks of STS and STW with walking speed or with step-length symmetry.
Bilateral Meningo-Cortical Involvement in Anti-myelin Oligodendrocyte Glycoprotein-IgG Associated Disorders: A Case Report
Authors: Ma Guozhong , He Jinzhao , Li Yan , Xu Yan , Hu Yunxin , Cui Fang
Published: May 2021

Cortical T2-weighted fluid-attenuated inversion recovery (FLAIR)-hyperintense lesions in anti-myelin oligodendrocyte glycoprotein (MOG)-associated encephalitis with seizures (FLAMES) are mostly unilateral and rarely spread to the bilateral cortex and meninges. We describe a case of MOG-immunoglobulin G (IgG) associated disorder (MOGAD) in a 39-year-old male with bilateral meningo-cortical involvement. The patient was hospitalized for epilepsy, fever, and headache. The initial MRI revealed abnormalities in the sulci of the bilateral frontal, temporal, and parietal lobes. He was considered to have infectious encephalitis and given empiric antibiotic and antiviral therapy, which were ineffective. His condition rapidly improved after the patient was switched to high-dose immunoglobulin therapy. No tests supported the presence of central nervous system (CNS) infections or autoimmune encephalitis. The second and third MRI scans showed reduced but still clearly observable meningo-cortical lesions. The patient was discharged without a definite diagnosis, but reported severe left vision impairment 25 days later. A fourth MRI showed signs typical of demyelinating CNS disease in addition to the original meningo-cortical lesions. The patient's symptoms were initially relieved by low-dose corticosteroid therapy, but they eventually returned, and he was re-admitted. The original lesions were diminished on the fifth MRI scan, but new lesions had developed in the deep white matter. A positive cell-based assay for MOG-IgG in serum confirmed MOGAD. The patient received high-dose corticosteroid treatment followed by an oral methylprednisolone taper, and his visual acuity gradually improved. The sixth and final MRI showed substantial decreases in the original lesions without new lesion formation. This unique case presents the complete diagnosis and treatment process for MOGAD with bilateral meningo-cortical involvement and may provide a reference for prompt diagnosis.
Translational Block in Stroke: A Constructive and “Out-of-the-Box” Reappraisal
Authors: Lourbopoulos Athanasios , Mourouzis Iordanis , Xinaris Christodoulos , Zerva Nefeli , Filippakis Konstantinos , Pavlopoulos Angelos , Pantos Constantinos
Published: May 2021

Why can we still not translate preclinical research to clinical treatments for acute strokes? Despite > 1000 successful preclinical studies, drugs, and concepts for acute stroke, only two have reached clinical translation. This is the translational block. Yet, we continue to routinely model strokes using almost the same concepts we have used for over 30 years. Methodological improvements and criteria from the last decade have shed some light but have not solved the problem. In this conceptual analysis, we review the current status and reappraise it by thinking “out-of-the-box” and over the edges. As such, we query why other scientific fields have also faced the same translational failures, to find common denominators. In parallel, we query how migraine, multiple sclerosis, and hypothermia in hypoxic encephalopathy have achieved significant translation successes. Should we view ischemic stroke as a “chronic, relapsing, vascular” disease, then secondary prevention strategies are also a successful translation. Finally, based on the lessons learned, we propose how stroke should be modeled, and how preclinical and clinical scientists, editors, grant reviewers, and industry should reconsider their routine way of conducting research. Translational success for stroke treatments may eventually require a bold change with solutions that are outside of the box.
Multiple Reaction Monitoring-Based Targeted Assays for the Validation of Protein Biomarkers in Brain Tumors
Authors: Ghantasala Saicharan , Pai Medha Gayathri J. , Biswas Deeptarup , Gahoi Nikita , Mukherjee Shuvolina , KP Manubhai , Nissa Mehar Un , Srivastava Alisha , Epari Sridhar , Shetty Prakash , Moiyadi Aliasgar , Srivastava Sanjeeva
Published: May 2021

The emergence of omics technologies over the last decade has helped in advancement of research and our understanding of complex diseases like brain cancers. However, barring genomics, no other omics technology has been able to find utility in clinical settings. The recent advancements in mass spectrometry instrumentation have resulted in proteomics technologies becoming more sensitive and reliable. Targeted proteomics, a relatively new branch of mass spectrometry-based proteomics has shown immense potential in addressing the shortcomings of the standard molecular biology-based techniques like Western blotting and Immunohistochemistry. In this study we demonstrate the utility of Multiple reaction monitoring (MRM), a targeted proteomics approach, in quantifying peptides from proteins like Apolipoprotein A1 (APOA1), Apolipoprotein E (APOE), Prostaglandin H2 D-Isomerase (PTGDS), Vitronectin (VTN) and Complement C3 (C3) in cerebrospinal fluid (CSF) collected from Glioma and Meningioma patients. Additionally, we also report transitions for peptides from proteins – Vimentin (VIM), Cystatin-C (CST3) and Clusterin (CLU) in surgically resected Meningioma tissues; Annexin A1 (ANXA1), Superoxide dismutase (SOD2) and VIM in surgically resected Glioma tissues; and Microtubule associated protein-2 (MAP-2), Splicing factor 3B subunit 2 (SF3B2) and VIM in surgically resected Medulloblastoma tissues. To our knowledge, this is the first study reporting the use of MRM to validate proteins from three types of brain malignancies and two different bio-specimens. Future studies involving a large cohort of samples aimed at accurately detecting and quantifying peptides of proteins with roles in brain malignancies could potentially result in a panel of proteins showing ability to classify and grade tumors. Successful application of these techniques could ultimately offer alternative strategies with increased accuracy, sensitivity and lower turnaround time making them translatable to the clinics.
The Application of and Factors Influencing, the NB5 Assay in Neuroblastomas
Authors: Wang Zuopeng , Wang Chengyun , Xu Yibing , Le Jun , Jiang Yuan , Yao Wei , Wang Hongsheng , Li Kai
Published: May 2021

Purpose

The NB5 assay was performed in bone marrow (BM) and peripheral blood (PB) to detect neuroblastomas (NBs) with micrometastases. The sensitivity and factors influencing the NB5 assay were preliminarily evaluated.

Methods

The NB5 assay uses RT-PCR to detect the co-expression of five mRNAs from the neuroblastoma-associated genes, CHGA, DCX, DDC, PHOX2B, and TH. We enrolled 180 cases of neuroblastoma and 65 cases of non-neuroblastoma. Bone marrow and peripheral blood were collected from every patient. The gold standard for the diagnosis of NB was pathological evaluation of solid tumor specimens or bone marrow biopsies (BMBs) from hematological tumors. STATA version 15 and SPSS version 17 software were used for analysis.

Results

We found that 17 patients were BMB (+), and they were diagnosed as the International Neuroblastoma Staging System (INSS) stage IV and the high-risk group. All 17 patients were BM (+), while 15 patients were PB (+) (15/17, 88.2%). Among the 163 children who were BMB (−), 56 were BM (+), 40 were PB (+), and 36 were BM (+) and PB (+). The sensitivity of the NB5 assay in BM (40.5%) and PB (30.5%) was significantly higher than the sensitivity of BMB (9.4%, P = 0.000). In the non-NB group, four cases were BM (+) and one case was PB (+). The specificity of the NB5 assay in BM and PB was 93.8% and 98.5%, respectively. The sensitivity of the NB5 assay in both BM and PB in INSS stage IV patients was significantly higher than that in INSS stage I–II patients (P <0.05). The sensitivity of the NB5 assay in both BM and PB in the high-risk group was significantly higher than that in the middle-low-risk groups (P = 0.0001). Logistic regression analyses indicated that liver metastases and bone metastases were the primary factors influencing the sensitivity of the NB5 assay in BM and PB (P <0.05).

Conclusions

The NB5 assay had significantly higher sensitivity than the pathological analysis of BMB in detecting NB with micrometastases. The NB5 assay had higher sensitivity in INSS stage IV or the high-risk group. Liver metastases and bone metastases were the primary factors that affected the sensitivity of the NB5 assay.