bluuebunny/crossref_metadata_2025 huggingface dataset:
Rate thresholds in cell signaling have functional and phenotypic consequences in non-linear time-dependent environments
Authors: Thiemicke Alexander , Neuert Gregor
Published: March 2023

All cells employ signal transduction pathways to respond to physiologically relevant extracellular cytokines, stressors, nutrient levels, hormones, morphogens, and other stimuli that vary in concentration and rate in healthy and diseased states. A central unsolved fundamental question in cell signaling is whether and how cells sense and integrate information conveyed by changes in the rate of extracellular stimuli concentrations, in addition to the absolute difference in concentration. We propose that different environmental changes over time influence cell behavior in addition to different signaling molecules or different genetic backgrounds. However, most current biomedical research focuses on acute environmental changes and does not consider how cells respond to environments that change slowly over time. As an example of such environmental change, we review cell sensitivity to environmental rate changes, including the novel mechanism of rate threshold. A rate threshold is defined as a threshold in the rate of change in the environment in which a rate value below the threshold does not activate signaling and a rate value above the threshold leads to signal activation. We reviewed p38/Hog1 osmotic stress signaling in yeast, chemotaxis and stress response in bacteria, cyclic adenosine monophosphate signaling in Amoebae, growth factors signaling in mammalian cells, morphogen dynamics during development, temporal dynamics of glucose and insulin signaling, and spatio-temproral stressors in the kidney. These reviewed examples from the literature indicate that rate thresholds are widespread and an underappreciated fundamental property of cell signaling. Finally, by studying cells in non-linear environments, we outline future directions to understand cell physiology better in normal and pathophysiological conditions.
Emerging roles of interferon-stimulated gene-15 in age-related telomere attrition, the DNA damage response, and cardiovascular disease
Authors: González-Amor María , Dorado Beatriz , Andrés Vicente
Published: March 2023

Population aging and age-related cardiovascular disease (CVD) are becoming increasingly prevalent worldwide, generating a huge medical and socioeconomic burden. The complex regulation of aging and CVD and the interaction between these processes are crucially dependent on cellular stress responses. Interferon-stimulated gene-15 (ISG15) encodes a ubiquitin-like protein expressed in many vertebrate cell types that can be found both free and conjugated to lysine residues of target proteins via a post-translational process termed ISGylation. Deconjugation of ISG15 (deISGylation) is catalyzed by the ubiquitin-specific peptidase 18 (USP18). The ISG15 pathway has mostly been studied in the context of viral and bacterial infections and in cancer. This minireview summarizes current knowledge on the role of ISG15 in age-related telomere shortening, genomic instability, and DNA damage accumulation, as well as in hypertension, diabetes, and obesity, major CVD risk factors prevalent in the elderly population.
Guided vs. conventional anti-platelet therapy for patients with acute coronary syndrome: A meta-analysis of randomized controlled trials
Authors: Zhong Peng-Yu , Deng Jian-Ping , Zhao Jing-Hong , Peng Lei , Liu Tao , Wang Hao-Yu
Published: March 2023

Background

Whether guided antiplatelet therapy in patients with acute coronary syndrome (ACS) is effective in improving net clinical benefits compared with conventional antiplatelet therapy remains controversial. Therefore, we assessed the safety and efficacy of guided antiplatelet therapy in patients with ACS and undergoing percutaneous coronary intervention.

Method

We searched PubMed, EMBASE, and Cochrane Library databases to select the relevant randomized controlled trials comparing the guided and conventional antiplatelet therapy in patients with ACS. The primary and safety outcomes are major adverse cardiovascular events (MACE) and major bleeding, respectively. The efficacy outcomes included myocardial infarction, stent thrombosis, all-cause death, and cardiovascular death. We selected the relative risk (RR) and 95% confidence intervals (CIs) as effect size and calculated it using the Review Manager software. In addition, we evaluated the final results by trial sequential analysis (registered by PROSPERO, CRD 42020210912).

Results

We selected seven randomized controlled trials and included 8,451 patients in this meta-analysis. Guided antiplatelet therapy can significantly reduce the risk of MACE (RR 0.64, 95% CI 0.54–0.76, P < 0.00001), myocardial infarction (RR 0.62, 95% CI 0.49–0.79, P = 0.0001), all-cause death (RR 0.61, 95% CI 0.44–0.85, P = 0.003), and cardiovascular death (RR 0.66, 0.49–0.90, P = 0.009). In addition, there is no significant difference between the two groups in stent thrombosis (RR 0.67, 95% CI 0.44–1.03, P = 0.07) and major bleeding (RR 0.86, 95% CI 0.65–1.13, P = 0.27). The subgroup analysis showed that the guided group based on genotype tests could bring benefits in MACE and myocardial infarction.

Conclusions

The guided antiplatelet therapy is not only associated with a comparable risk of bleeding but also with a lower risk of MACE, myocardial infarction, all-cause death, cardiovascular death, and stent thrombosis than the conventional strategy in patients with ACS.
Insertable cardiac monitor with a long sensing vector: Impact of obesity on sensing quality and safety
Authors: Bisignani Giovanni , De Bonis Silvana , Pierre Bertrand , Lau Dennis H. , Hofer Daniel , Sanfins Victor Manuel , Hain Andreas , Cabanas Pilar , Martens Eimo , Berruezo Antonio , Eschalier Romain , Milliez Paul , Lüsebrink Ulrich , Mansourati Jacques , Papaioannou Georgios , Giacopelli Daniele , Gargaro Alessio , Ploux Sylvain
Published: March 2023

Background

Fat layers in obese patients can impair R-wave detection and diagnostic performance of a subcutaneous insertable cardiac monitor (ICM). We compared safety and ICM sensing quality between obese patients [body mass index (BMI) ≥ 30 kg/m2] and normal-weight controls (BMI <30 kg/m2) in terms of R-wave amplitude and time in noise mode (noise burden) detected by a long-sensing-vector ICM.

Materials and methods

Patients from two multicentre, non-randomized clinical registries are included in the present analysis on January 31, 2022 (data freeze), if the follow-up period was at least 90 days after ICM insertion, including daily remote monitoring. The R-wave amplitudes and daily noise burden averaged intraindividually for days 61–90 and days 1–90, respectively, were compared between obese patients (n = 104) and unmatched (n = 268) and a nearest-neighbour propensity score (PS) matched (n = 69) normal-weight controls.

Results

The average R-wave amplitude was significantly lower in obese (median 0.46 mV) than in normal-weight unmatched (0.70 mV, P < 0.0001) or PS-matched (0.60 mV, P = 0.003) patients. The median noise burden was 1.0% in obese patients, which was not significantly higher than in unmatched (0.7%; P = 0.056) or PS-matched (0.8%; P = 0.133) controls. The rate of adverse device effects during the first 90 days did not differ significantly between groups.

Conclusion

Although increased BMI was associated with reduced signal amplitude, also in obese patients the median R-wave amplitude was >0.3 mV, a value which is generally accepted as the minimum level for adequate R-wave detection. The noise burden and adverse event rates did not differ significantly between obese and normal-weight patients.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04075084 and NCT04198220.
Finding patterns of atoll morphometrics at a range of spatial scales
Authors: Johnson Faith M. , Ortiz Alejandra C.
Published: March 2023

Small Island Nations, often comprised of Atolls, are at considerable risk of climate change impacts from sea-level rise to coral acidification to increasing cyclone intensity; understanding how they will change in the coming century is vital for climate mitigation and resiliency. However, the morphology of atolls are not well quantified or summarized. In this work, we calculate modern atoll morphometrics on a global scale including 3,786 motu and 593 reef flats on 154 atolls. Temporal composites of Landsat imagery are created for 4 years (2015–2018), and are classified into motu, reef flat, open water/lagoon via unsupervised classification. Morphometrics, including widths, lengths, and area, are computed for each motu and reef flat of the atoll in Python, creating a database of atolls and their associated morphometrics. Consistency in automated processing of atoll morphometrics removes spatial and user bias, enabling a better understanding of geographic patterns of atoll area and other morphometrics. Distinct differences in the distribution of motu are seen on a regional scale in French Polynesia, while globally, wider reef flats and larger motu are found closest to the equator. Globally, there is a consistent reef flat width in front of large motu (>1 km length) of 184 ± 93 m (n = 724). Our atoll morphometric database creates a baseline of current atoll characteristics that can be expanded upon in the future and used for evaluating temporal changes to atoll islands.
Lipocalin 2 – mutation screen and serum levels in patients with anorexia nervosa or obesity and in lean individuals
Authors: Zheng Yiran , Rajcsanyi Luisa Sophie , Kowalczyk Manuela , Giuranna Johanna , Herpertz-Dahlmann Beate , Seitz Jochen , de Zwaan Martina , Herzog Wolfgang , Ehrlich Stefan , Zipfel Stephan , Giel Katrin , Egberts Karin , Burghardt Roland , Föcker Manuel , Al-Lahham Saad , Hebebrand Johannes , Fuhrer Dagmar , Tan Susanne , Zwanziger Denise , Peters Triinu , Hinney Anke
Published: March 2023

Context

The bone-derived adipokine lipocalin-2 is relevant for body weight regulation by stimulating the leptin-melanocortin pathway.

Objective

We aimed to (i) detect variants in the lipocalin-2 gene (LCN2) which are relevant for body weight regulation and/or anorexia nervosa (AN); (ii) describe and characterize the impact of LCN2 and MC4R variants on circulating lipocalin-2 level.

Methods

Sanger sequencing of the coding region of LCN2 in 284 children and adolescents with severe obesity or 287 patients with anorexia nervosa. In-silico analyses to evaluate functional implications of detected LCN2 variants. TaqMan assays for rare non-synonymous variants (NSVs) in additional independent study groups. Serum levels of lipocalin-2 were measured by ELISA in 35 females with NSVs in either LCN2 or MC4R, and 33 matched controls without NSVs in the two genes.

Results

Fourteen LCN2-variants (five NSVs) were detected. LCN2-p.Leu6Pro and p.Gly9Val located in the highly conserved signal peptide region may induce functional consequences. The secondary structure change of lipocalin-2 due to LCN2-p.Val89Ile may decrease solubility and results in a low lipocalin-2 level in a heterozygotes carrier (female recovered from AN). Lean individuals had lower lipocalin-2 levels compared to patients with obesity (p = 0.033).

Conclusion

Lipocalin-2 levels are positively associated with body mass index (BMI). Single LCN2-variants might have a profound effect on lipocalin-2 levels.
The crossroad between autoimmune disorder, tissue remodeling and cancer of the thyroid: The long pentraxin 3 (PTX3)
Authors: Chiari Damiano , Pirali Barbara , Perano Vittoria , Leone Roberto , Mantovani Alberto , Bottazzi Barbara
Published: March 2023

Thyroid is at the crossroads of immune dysregulation, tissue remodeling and oncogenesis. Autoimmune disorders, nodular disease and cancer of the thyroid affect a large amount of general population, mainly women. We wondered if there could be a common factor behind three processes (immune dysregulation, tissue remodeling and oncogenesis) that frequently affect, sometimes coexisting, the thyroid gland. The long pentraxin 3 (PTX3) is an essential component of the humoral arm of the innate immune system acting as soluble pattern recognition molecule. The protein is found expressed in a variety of cell types during tissue injury and stress. In addition, PTX3 is produced by neutrophils during maturation in the bone-marrow and is stored in lactoferrin-granules. PTX3 is a regulator of the complement cascade and orchestrates tissue remodeling and repair. Preclinical data and studies in human tumors indicate that PTX3 can act both as an extrinsic oncosuppressor by modulating complement-dependent tumor-promoting inflammation, or as a tumor-promoter molecule, regulating cell invasion and proliferation and epithelial to mesenchymal transition, thus suggesting that this molecule may have different functions on carcinogenesis. The involvement of PTX3 in the regulation of immune responses, tissue remodeling and oncosuppressive processes led us to explore its potential role in the development of thyroid disorders. In this review, we aimed to highlight what is known, at the state of the art, regarding the connection between the long pentraxin 3 and the main thyroid diseases i.e., nodular thyroid disease, thyroid cancer and autoimmune thyroid disorders.
Spatial–temporal QoS assessment of the EV charging network considering power outages
Authors: Tang Difei , Liu Xiaofeng , Zhao Tianyang , Wang Qi
Published: March 2023

The rapid expansion of electric vehicle charging networks (EVCNs) makes them critical infrastructures bridging power and traffic systems. The EVCN could be vulnerable during power outages at fast charging stations (FCSs), which are induced by planned maintenance or emergency load shedding. This paper proposes an approach to assess the impact of power outages on the Quality-of-service of the EVCN. The Markov decision process is utilized to model the spatial–temporal randomness of EV movement in a graph-based EVCN. The decision of charging by EV drivers is estimated by a fuzzy logic inference system. The spatial–temporal EV charging load at FCSs is formulated by a queuing-based non-linear optimization problem. Yen’s algorithm is adopted to simulate the EV redistribution phenomenon of searching adjacent healthy FCSs in response to the power outage. Quality-of-service (QoS) indices are derived to assess the potential congestions in the adjacent healthy FCSs. The case studies demonstrate that power outages may cause congestion at peripheral FCSs, exacerbating the QoS of the EVCN. Partial charging may alleviate the QoS deterioration in the event of FCS outages.
Prospects and challenges of regional modeling frameworks to inform planning for food, energy, and water systems: Views of modelers and stakeholders
Authors: Tuler Seth P. , Webler Thomas , Hansen Robin , Vörösmarty Charles J. , Melillo Jerry M. , Wuebbles Donald J.
Published: March 2023

Multisectoral models of regional bio-physical systems simulate policy responses to climate change and support climate mitigation and adaptation planning at multiple scales. Challenges facing these efforts include sometimes weak understandings of causal relationships, lack of integrated data streams, spatial and temporal incongruities with policy interests, and how to incorporate dynamics associated with human values, governance structures, and vulnerable populations. There are two general approaches to developing integrated models. The first involves stakeholder involvement in model design -- a participatory modeling approach. The second is to integrate existing models. This can be done in two ways: by integrating existing models or by a soft-linked confederation of existing models. A benefit of utilizing existing models is the leveraging of validated and familiar models that provide credibility. We report opportunities and challenges manifested in one effort to develop a regional food, energy, and water systems (FEWS) modeling framework using existing bio-physical models. The C-FEWS modeling framework (Climate-induced extremes on the linked food, energy, water system) is intended to identify and evaluate response options to extreme weather in the Midwest and Northeast United States thru the year 2100. We interviewed ten modelers associated with development of the C-FEWS framework and ten stakeholders from government agencies, planning agencies, and non-governmental organizations in New England. We inquired about their perspectives on the roles and challenges of regional FEWS modeling frameworks to inform planning and information needed to support planning in integrated food, energy, and water systems. We also analyzed discussions of meetings among modelers and among stakeholders and modelers. These sources reveal many agreements among modelers and stakeholders about the role of modeling frameworks, their benefits for policymakers, and the types of outputs they should produce. They also identify challenges to developing regional modeling frameworks that couple existing models and balancing model capabilities with stakeholder preferences for information. The results indicate the importance of modelers and stakeholders engaging in dialogue to craft modeling frameworks and scenarios that are credible and relevant for policymakers. We reflect on the implications for how FEWS modeling frameworks comprised of existing bio-physical models can be designed to better inform policy making at the regional scale.
Using existing infrastructure as ground control points to support citizen science coastal UAS monitoring programs
Authors: Rabins Lucas F. , Theuerkauf Ethan J. , Bunting Erin L.
Published: March 2023

Recent publications have described the ability of citizen scientists to conduct unoccupied aerial system (UAS) flights to collect data for coastal management. Ground control points (GCPs) can be collected to georeference these data, however collecting ground control points require expensive surveying equipment not accessible to citizen scientists. Instead, existing infrastructure can be used as naturally occurring ground control points (NGCPs), although availably of naturally occurring ground control point placement on such infrastructure differs from published best practices of ground control point placement. This study therefore evaluates the achievable accuracy of sites georeferenced with naturally occurring ground control points through an analysis of 20 diverse coastal sites. At most sites naturally occurring ground control points produced horizontal and vertical root mean square errors (RMSE) less than 0.060 m which are similar to those obtained using traditional ground control points. To support future unoccupied aerial system citizen science coastal monitoring programs, an assessment to determine the optimal naturally occurring ground control point quantity and distribution was conducted for six coastal sites. Results revealed that generally at least seven naturally occurring ground control points collected in the broadest distribution across the site will result in a horizontal and vertical root mean square errors less than 0.030 m and 0.075 m respectively. However, the relationship between these placement characteristics and root mean square errors was poor, indicating that georeferencing accuracy using naturally occurring ground control points cannot be optimized solely through ideal quantity and distribution. The results of these studies highlight the value of naturally occurring ground control points to support unoccupied aerial system citizen science coastal monitoring programs, however they also indicate a need for an initial accuracy assessment of sites surveyed with naturally occurring ground control points at the onset of such programs.
Collaborating on ESG consulting, reporting, and communicating education: Using partner maps for capability building design
Authors: Liao Han-Teng , Pan Chung-Lien , Zhang Yuan
Published: March 2023

Given the rising demand for environmental, social, and governance (ESG) talents, this study aims to provide a multidisciplinary outlook of specific capability requirements for ESG talents, focusing on the use of ESG and carbon information, thereby providing a roadmap for ESG education. Following design science framework conventions and running design workshops that integrate design thinking of “how might we” design questions, literature analysis, and expert interviews across disciplines, this study presents findings regarding three main activities—consulting, reporting, and communicating. Based on the iterations of design workshops that adopt a circular economy-based partner map design canvas for stakeholder analysis with procedures such as expert interviews and literature analysis, three partner/capability maps were generated to map stakeholders and explore the capabilities needed. ESG and carbon information digital and data skills emerged as the core capability to complete all the three tasks. A conceptual framework—a Smart System of ESG and Carbon Information—is proposed to summarize planning, operating, and communicating with ESG and carbon information, along with high-level organizational actions and talent capabilities. It identifies the building blocks of an ESG operating system within an enterprise to engage various stakeholders for value-creation collaboration. Despite the limitation of a lack of comprehensive review and limited geographic and disciplinary representation, this study provides a roadmap for enterprises and universities to explore and define talent requirements and create specific education and training programs.
Growth of Stipa breviflora does not respond to nitrogen addition because of its conservative nitrogen utilization
Authors: Zhao Kun , Gao Hui , Sun Zhi , Zhang Junling , Li Haigang
Published: March 2023

Enhanced atmospheric nitrogen (N) deposition is threating species diversity in the desert steppe ecoregions. Needlegrass (Stipa breviflora) is the dominant specie in the desert steppe grasslands of China and southern Mongolia, and the response of S. brevifolia to N deposition is not well known. In this study, we conducted an experiment to determine the growth and N uptake of S. breviflora in response to several N addition rates. The results showed that N addition did not change plant growth, emergence rate, plant height, or biomass of S. breviflora, even at a N addition rate of 50 kg N ha−1 yr.−1 with sufficient soil moisture during a 120-day growth period. The absence of a N effect was due to the fact that N uptake in S. breviflora was not improved by N addition. These results indicated that S. breviflora is very conservative with respect to N utilization, which could possibly help it resist enhanced atmospheric N deposition. Moreover, conservative N utilization also enables S. breviflora to survive in N-limiting soils.
A flagellin-conjugate protein induces dual NLRC4- and NLRP3-inflammasome activation which modulates inflammatory cytokine secretion from macrophages
Authors: Lin Yen-Ju , Jamin Annette , Wolfheimer Sonja , Fiedler Anna , Junker Ann-Christine , Goretzki Alexandra , Scheurer Stephan , Schülke Stefan
Published: March 2023

Background

A recombinant fusion protein combining the adjuvant and TLR5-ligand flagellin with the major birch pollen allergen Bet v 1 (rFlaA:Betv1) has been suggested to prevent the manifestation of birch allergy. Noteworthy, rFlaA:Betv1 induced both pro- and anti-inflammatory responses which were differentially regulated. However, the mechanism by which flagellin fusion proteins modulate allergen-specific immune responses, especially the mechanisms underlying IL-1β secretion and their contribution to the overall immune responses remains elusive.

Objective

To investigate the mechanisms underlying the production of IL-1β from rFlaA:Betv1 stimulated macrophages.

Methods

Macrophages were derived from mouse peritoneal-, human buffy-coat-, and PMA-differentiated THP-1 (wild type or lacking either ASC, NLRP3, or NLRC4) cells. Macrophages were stimulated with non-modified rFlaA:Betv1, mutant variants lacking either the flagellin DC0 domain or a sequence motif formerly described to mediate TLR5-activation, and respective controls in the presence or absence of inhibitors interfering with MAPK- and NFκB-signaling. Cytokine secretion was analyzed by ELISA and intracellular signaling by Western Blot. To study the contribution of IL-1β to the overall immune responses, IL1R-deficient mouse peritoneal macrophages were used.

Results

rFlaA:Betv1 consistently activated all types of investigated macrophages, inducing higher IL-1β secretion compared with the equimolar mixture of both proteins. rFlaA:Betv1-induced activation of THP-1 macrophages was shown to be independent of either the TLR5-activating sequence motif or the flagellin DC0 domain but depended on both NLRP3- and NLRC4-inflammasomes. In addition, NFκB and SAP/JNK MAP kinases regulated rFlaA:Betv1-induced inflammasome activation and cytokine secretion by modulating pro-Caspase-1- and pro-IL-1β-expression in THP-1 macrophages. Finally, lack of IL-1β positive feedback via the IL1R strongly diminished the rFlaA:Betv1-induced secretion of IL-1β, IL-6, and TNF-α from peritoneal macrophages.

Conclusion

The mechanisms contributing to rFlaA:Betv1-induced IL-1β secretion from macrophages were shown to be complex, involving both NLRC4- and NLRP3-inflammsomes, as well as NFκB- and SAP/JNK MAP kinase-signaling. Better understanding the mechanisms regulating the activation of immune cells by novel therapeutic candidates like the rFlaA:Betv1 fusion protein will allow us to further improve and develop new treatment strategies when using flagellin as an adjuvant.
The peculiar challenge of bringing CAR-T cells into the brain: Perspectives in the clinical application to the treatment of pediatric central nervous system tumors
Authors: Del Baldo Giada , Del Bufalo Francesca , Pinacchio Claudia , Carai Andrea , Quintarelli Concetta , De Angelis Biagio , Merli Pietro , Cacchione Antonella , Locatelli Franco , Mastronuzzi Angela
Published: March 2023

Childhood malignant brain tumors remain a significant cause of death in the pediatric population, despite the use of aggressive multimodal treatments. New therapeutic approaches are urgently needed for these patients in order to improve prognosis, while reducing side effects and long-term sequelae of the treatment. Immunotherapy is an attractive option and, in particular, the use of gene-modified T cells expressing a chimeric antigen receptor (CAR-T cells) represents a promising approach. Major hurdles in the clinical application of this approach in neuro-oncology, however, exist. The peculiar location of brain tumors leads to both a difficulty of access to the tumor mass, shielded by the blood-brain barrier (BBB), and to an increased risk of potentially life-threatening neurotoxicity, due to the primary location of the disease in the CNS and the low intracranial volume reserve. There are no unequivocal data on the best way of CAR-T cell administration. Multiple trials exploring the use of CD19 CAR-T cells for hematologic malignancies proved that genetically engineered T cells can cross the BBB, suggesting that systemically administered CAR-T cell can be used in the neuro-oncology setting. Intrathecal and intra-tumoral delivery can be easily managed with local implantable devices, suitable also for a more precise neuro-monitoring. The identification of specific approaches of neuro-monitoring is of utmost importance in these patients. In the present review, we highlight the most relevant potential challenges associated with the application of CAR-T cell therapy in pediatric brain cancers, focusing on the evaluation of the best route of delivery, the peculiar risk of neurotoxicity and the related neuro-monitoring.
Autoimmune encephalitis with mGluR5 antibodies: A case series from China and review of the literature
Authors: Guo Kundian , Liu Xu , Gong Xue , Li Aiqing , Liu Yue , Li Xingjie , Zhou Dong , Hong Zhen
Published: March 2023

Background

Only 15 patients of autoimmune encephalitis with metabotropic glutamate receptor 5 (mGluR5) antibodies have been reported worldwide since 2011, mostly from western countries. Patients with different genetic backgrounds are necessary to further clarify the clinical phenotype and prognosis of this rare disease.

Objective

We initially describe a case series from China to confirm the previous findings, expand the clinical phenotype, and identify the prognostic factors of autoimmune encephalitis with mGluR5 antibodies.

Methods

Observational data with follow-up were prospectively collected from autoimmune encephalitis patients with mGluR5 antibodies. Clinical information and outcomes on current and previously reported cases were combined and analyzed.

Results

We identified five patients (median age 35 years); two were female. The main clinical manifestations were behavioral/personality changes (five of five, 100%) and cognitive disorders (four of five, 80%), accompanied with other neurologic symptoms. Hypoventilation occurred in two (40%) patients, which was life-threatening. One patient had meningoencephalitis, suggesting a new phenotype in anti-mGluR5 encephalitis. All patients received immunotherapy. At the last follow-up (median 18 months), two (40%) patients showed complete recovery, two (40%) patients showed partial recovery, and one (20%) patient died. One (20%) patient had multiple relapses. Together with the 15 previously reported cases, associated tumors occurred in seven of 12 (58%) Western patients vs. one of eight (13%) Chinese patients. Modified Rankin Scale (mRS) scores at the last follow-up (median 31 months) were available in 16 patients. Patients with bad outcomes (mRS > 2, n = 4) were more likely to have hypoventilation at onset and higher mRS scores at peak of the disease.

Conclusions

In patients with different genetic background, as Chinese, the clinical phenotype of anti-mGluR5 encephalitis is similar. Fewer paraneoplastic cases were observed in Chinese patients. Most patients showed good responses to immunotherapy and cancer treatment. The clinical outcomes were favorable in most patients.
Forecasting Prorocentrum minimum blooms in the Chesapeake Bay using empirical habitat models
Authors: Horemans Dante M. L. , Friedrichs Marjorie A. M. , St-Laurent Pierre , Hood Raleigh R. , Brown Christopher W.
Published: March 2023

Aquaculturists, local beach managers, and other stakeholders require forecasts of harmful biotic events, so they can assess and respond to health threats when harmful algal blooms (HABs) are present. Based on this need, we are developing empirical habitat suitability models for a variety of Chesapeake Bay HABs to forecast their occurrence based on a set of physical-biogeochemical environmental conditions, and start with the dinoflagellate Prorocentrum minimum (also known as P. cordatum).To identify an optimal set of environmental variables to forecast P. minimum blooms, we first assumed a linear relationship between the environmental variables and the inverse of the logistic function used to forecast the likelihood of bloom presence, and repeated the method using more than 16,000 combinations of variables. By comparing goodness-of-fit, we found water temperature, salinity, pH, solar irradiance, and total organic nitrogen represented the most suitable set of variables. The resulting algorithm forecasted P. minimum blooms with an overall accuracy of 78%, though with a significant variability ~ 30-90% depending on region and season. To understand this variability and improve model performance, we incorporated nonlinear effects into the model by implementing a generalized additive model. Even without considering interactions between the five variables used to train the model, this yielded an increase in overall model accuracy (~ 81%) due to the model’s ability to refine the regions in which P. minimum blooms occurred. Including nonlinear interactions increased the overall model accuracy even further (~ 85%) by accounting for seasonality in the interaction between solar irradiance and water temperature. Our findings suggest that the influence of predictors of these blooms change in time and space, and that model complexity impacts the model performance and our interpretation of the driving factors causing P. minimum blooms. Apart from their forecasting potential, our results may be particularly useful when constructing explicit relationships between environmental conditions and P. minimum presence in mechanistic models.
Clostridium tyrobutyricum occurrence in silages and cattle feed: Use of molecular and simulation data to optimize predictive models
Authors: Mosconi Martina , Fontana Alessandra , Daza Mireya Viviana Belloso , Bassi Daniela , Gallo Antonio
Published: March 2023

Introduction

Poor quality silage can derive from the presence of deleterious microorganisms such as clostridia. Their dissemination along the food chain, especially in milk, causes issues such as the cheese late-blowing defect, particularly triggered by Clostridium tyrobutyricum. The scope of our study was to determine the C. tyrobutyricum occurrence in three different farms across four time periods in relation to the animal diets, specifically the Total Mixed Ration (TMR), by using real-time PCR.

Methods

For this purpose, molecular-derived data were exploited to optimize a predictive model that simulated the farm conditions favoring the growth of butyric acid bacteria such as C. tyrobutyricum.

Results

Our results showed that the originally utilized predictive model strongly underestimated the growth of C. tyrobutyricum in comparison to the molecular data. At the same time, our findings uncovered an additional source of contamination in the TMR related to silage and dietary residues that represent a reservoir of microbial contamination during successive TMR preparation. Based on these findings, the optimization of the model parameters such as growth rate range and the inclusion of the residues in the model, allowed a more accurate prediction of the contamination levels. Therefore, this study revealed that proper hygiene practices such as the removal of silage and TMR residues within the farm environment is essential to control the contamination by C. tyrobutyricum and avoid food waste and economic losses.
Modulation of the biological network of lumbar spinal stenosis by Tongdu Huoxue Decoction based on clinical metabolomics
Authors: Ji Luhong , Huang Ping , Wang Qiong , Li Xugui , Li Ying
Published: March 2023

Objective: To explore the clinical efficacy and metabolic mechanism of Tongdu Huoxue Decoction (THD) in treating lumbar spinal stenosis (LSS).

Methods: A total of 40 LSS patients and 20 healthy participants were recruited from January 2022 to June 2022. The patients’ pre- and post-treatment visual analogue scale (VAS) and Japanese Orthopaedic Association (JOA) scores were recorded. ELISA kits were used to assess pre- and post-treatment levels of serum Interleukin-1beta (IL-1β), Alpha tumour necrosis factor (TNF-α) and prostaglandin E2 (PGE2). Finally, the patients’ pre- and post-treatment and healthy human sera were subjected to extensively targeted metabolomics using Ultra Performance Liquid Chromatography (UPLC) to identify potential differential metabolites and metabolic pathways using multivariate statistical analysis.

Results: Compared to the pre-treatment (group A), the patients’ VAS scores decreased significantly (p < 0.05), while JOA scores increased significantly (p < 0.05) post-treatment (group B), indicating that THD could effectively improve the pain and lumbar spine function of LSS patients. Moreover, THD could effectively inhibit the expression of IL-1β, TNF-α and PGE2-associated inflammatory factors in serum. Regarding metabolomics, the levels of 41 differential metabolites were significantly different in the normal group (group NC) compared to group A, and those were significantly restored after treatment with THD, including chenodeoxycholic acid 3-sulfate, taurohyodeoxycholic acid, 3,5-Dihydroxy-4-methoxybenzoic acid, pinocembrin. These biomarkers are mainly involved in purine metabolism, steroid hormone biosynthesis and amino acid metabolism.

Conclusion: This clinical trial demonstrated that THD is effective in improving pain, lumbar spine function and serum levels of inflammation in patients with LSS. Moreover, its mechanism of action is related to the regulation of purine metabolism, steroid hormone biosynthesis and the expression of key biomarkers in the metabolic pathway of amino acid metabolism.
Interoceptive awareness: MBSR training alters information processing of salience network
Authors: Guu Shiao-Fei , Chao Yi-Ping , Huang Feng-Ying , Cheng Yu-Ting , Ng Hei-Yin Hydra , Hsu Chia-Fen , Chuang Chun-Hsiang , Huang Chih-Mao , Wu Changwei W.
Published: March 2023

Mindfulness refers to a mental state of awareness of internal experience without judgment. Studies have suggested that each mindfulness practice may involve a unique mental state, but the underlying neurophysiological mechanisms remain unknown. Here we examined how distinct mindfulness practices after mindfulness-based intervention alter brain functionality. Specifically, we investigated the functional alterations of the salience network (SN) using functional magnetic resonance imaging (fMRI) among the two interoceptive mindfulness practices—breathing and body scan—associated with interoceptive awareness in fixed attention and shifted attention, respectively. Long-distance functional connectivity (FC) and regional homogeneity (ReHo) approaches were applied to measure distant and local neural information processing across various mental states. We hypothesized that mindful breathing and body scan would yield a unique information processing pattern in terms of long-range and local functional connectivity (FC). A total of 18 meditation-naïve participants were enrolled in an 8-week mindfulness-based stress reduction (MBSR) program alongside a waitlist control group (n = 14), with both groups undergoing multiple fMRI sessions during breathing, body scan and resting state for comparison. We demonstrated that two mindfulness practices affect both the long-distance FCSN and the local ReHo, only apparent after the MBSR program. Three functional distinctions between the mindfulness practices and the resting state are noted: (1) distant SN connectivity to occipital regions increased during the breathing practice (fixed attention), whereas the SN increased connection with the frontal/central gyri during the body scan (shifting attention); (2) local ReHo increased only in the parietal lobe during the body scan (shifting attention); (3) distant and local connections turned into a positive correlation only during the mindfulness practices after the MBSR training, indicating a global enhancement of the SN information processing during mindfulness practices. Though with limited sample size, the functional specificity of mindfulness practices offers a potential research direction on neuroimaging of mindfulness, awaiting further studies for verification.
Locus coeruleus noradrenergic neurons phase-lock to prefrontal and hippocampal infra-slow rhythms that synchronize to behavioral events
Authors: Xiang Liyang , Harel Antoine , Todorova Ralitsa , Gao HongYing , Sara Susan J. , Wiener Sidney I.
Published: March 2023

The locus coeruleus (LC) is the primary source of noradrenergic projections to the forebrain, and, in prefrontal cortex, is implicated in decision-making and executive function. LC neurons phase-lock to cortical infra-slow wave oscillations during sleep. Such infra-slow rhythms are rarely reported in awake states, despite their interest, since they correspond to the time scale of behavior. Thus, we investigated LC neuronal synchrony with infra-slow rhythms in awake rats performing an attentional set-shifting task. Local field potential (LFP) oscillation cycles in prefrontal cortex and hippocampus on the order of 0.4 Hz phase-locked to task events at crucial maze locations. Indeed, successive cycles of the infra-slow rhythms showed different wavelengths, as if they are periodic oscillations that can reset phase relative to salient events. Simultaneously recorded infra-slow rhythms in prefrontal cortex and hippocampus could show different cycle durations as well, suggesting independent control. Most LC neurons (including optogenetically identified noradrenergic neurons) recorded here were phase-locked to these infra-slow rhythms, as were hippocampal and prefrontal units recorded on the LFP probes. The infra-slow oscillations also phase-modulated gamma amplitude, linking these rhythms at the time scale of behavior to those coordinating neuronal synchrony. This would provide a potential mechanism where noradrenaline, released by LC neurons in concert with the infra-slow rhythm, would facilitate synchronization or reset of these brain networks, underlying behavioral adaptation.
A review of stress-induced hyperglycaemia in the context of acute ischaemic stroke: Definition, underlying mechanisms, and the status of insulin therapy
Authors: Yao Mengyue , Hao Yulei , Wang Tian , Xie Meizhen , Li Hui , Feng Jiachun , Feng Liangshu , Ma Di
Published: March 2023

The transient elevation of blood glucose produced following acute ischaemic stroke (AIS) has been described as stress-induced hyperglycaemia (SIH). SIH is common even in patients with AIS who have no previous diagnosis of diabetes mellitus. Elevated blood glucose levels during admission and hospitalization are strongly associated with enlarged infarct size and adverse prognosis in AIS patients. However, insulin-intensive glucose control therapy defined by admission blood glucose for SIH has not achieved the desired results, and new treatment ideas are urgently required. First, we explore the various definitions of SIH in the context of AIS and their predictive value in adverse outcomes. Then, we briefly discuss the mechanisms by which SIH arises, describing the dual effects of elevated glucose levels on the central nervous system. Finally, although preclinical studies support lowering blood glucose levels using insulin, the clinical outcomes of intensive glucose control are not promising. We discuss the reasons for this phenomenon.
Acupuncture treatment for post-stroke depression: Intestinal microbiota and its role
Authors: Jiang Hailun , Deng Shizhe , Zhang Jieying , Chen Junjie , Li Boxuan , Zhu Weiming , Zhang Menglong , Zhang Chao , Meng Zhihong
Published: March 2023

Stroke-induced depression is a common complication and an important risk factor for disability. Besides psychiatric symptoms, depressed patients may also exhibit a variety of gastrointestinal symptoms, and even take gastrointestinal symptoms as the primary reason for medical treatment. It is well documented that stress may disrupt the balance of the gut microbiome in patients suffering from post-stroke depression (PSD), and that disruption of the gut microbiome is closely related to the severity of the condition in depressed patients. Therefore, maintaining the balance of intestinal microbiota can be the focus of research on the mechanism of acupuncture in the treatment of PSD. Furthermore, stroke can be effectively treated with acupuncture at all stages and it may act as a special microecological regulator by regulating intestinal microbiota as well. In this article, we reviewed the studies on changing intestinal microbiota after acupuncture treatment and examined the existing problems and development prospects of acupuncture, microbiome, and poststroke depression, in order to provide new ideas for future acupuncture research.
Cortical processing during robot and functional electrical stimulation
Authors: Cho Woosang , Vidaurre Carmen , An Jinung , Birbaumer Niels , Ramos-Murguialday Ander
Published: March 2023

Introduction

Like alpha rhythm, the somatosensory mu rhythm is suppressed in the presence of somatosensory inputs by implying cortical excitation. Sensorimotor rhythm (SMR) can be classified into two oscillatory frequency components: mu rhythm (8–13 Hz) and beta rhythm (14–25 Hz). The suppressed/enhanced SMR is a neural correlate of cortical activation related to efferent and afferent movement information. Therefore, it would be necessary to understand cortical information processing in diverse movement situations for clinical applications.

Methods

In this work, the EEG of 10 healthy volunteers was recorded while fingers were moved passively under different kinetic and kinematic conditions for proprioceptive stimulation. For the kinetics aspect, afferent brain activity (no simultaneous volition) was compared under two conditions of finger extension: (1) generated by an orthosis and (2) generated by the orthosis simultaneously combined and assisted with functional electrical stimulation (FES) applied at the forearm muscles related to finger extension. For the kinematic aspect, the finger extension was divided into two phases: (1) dynamic extension and (2) static extension (holding the extended position).

Results

In the kinematic aspect, both mu and beta rhythms were more suppressed during a dynamic than a static condition. However, only the mu rhythm showed a significant difference between kinetic conditions (with and without FES) affected by attention to proprioception after transitioning from dynamic to static state, but the beta rhythm was not.

Discussion

Our results indicate that mu rhythm was influenced considerably by muscle kinetics during finger movement produced by external devices, which has relevant implications for the design of neuromodulation and neurorehabilitation interventions.
Individual or mixing extrusion of Tartary buckwheat and adzuki bean: Effect on quality properties and starch digestibility of instant powder
Authors: Zhang Zhuo , Liang Yongqiang , Zou Liang , Xu Yunan , Li Mengzhuo , Xing Bao , Zhu Manli , Hu Yichen , Ren Guixing , Zhang Lizhen , Qin Peiyou
Published: March 2023

Introduction

Tartary buckwheat and adzuki bean, which are classified as coarse grain, has attracted increasing attention as potential functional ingredient or food source because of their high levels of bioactive components and various health benefits.

Methods

This work investigated the effect of two different extrusion modes including individual extrusion and mixing extrusion on the phytochemical compositions, physicochemical properties and in vitro starch digestibility of instant powder which consists mainly of Tartary buckwheat and adzuki bean flour.

Results

Compared to mixing extrusion, instant powder obtained with individual extrusion retained higher levels of protein, resistant starch, polyphenols, flavonoids and lower gelatinization degree and estimated glycemic index. The α-glucosidase inhibitory activity (35.45%) of the instant powder obtained with individual extrusion was stronger than that obtained with mixing extrusion (26.58%). Lower levels of digestibility (39.65%) and slower digestion rate coefficient (0.25 min−1) were observed in the instant powder obtained with individual extrusion than in mixing extrusion (50.40%, 0.40 min−1) by logarithm-of-slope analysis. Moreover, two extrusion modes had no significant impact on the sensory quality of instant powder. Correlation analysis showed that the flavonoids were significantly correlated with physicochemical properties and starch digestibility of the instant powder.

Discussion

These findings suggest that the instant powder obtained with individual extrusion could be used as an ideal functional food resource with anti-diabetic potential.