bluuebunny/crossref_metadata_2025 huggingface dataset:
A Real-Time Wearable System for Monitoring Vital Signs of COVID-19 Patients in a Hospital Setting
Authors: Santos Mauro D. , Roman Cristian , Pimentel Marco A. F. , Vollam Sarah , Areia Carlos , Young Louise , Watkinson Peter , Tarassenko Lionel
Published: September 2021

The challenges presented by the Coronavirus disease 2019 (COVID-19) pandemic to the National Health Service (NHS) in the United Kingdom (UK) led to a rapid adaptation of infection disease protocols in-hospital. In this paper we report on the optimisation of our wearable ambulatory monitoring system (AMS) to monitor COVID-19 patients on isolation wards. A wearable chest patch (VitalPatch®, VitalConnect, United States of America, USA) and finger-worn pulse oximeter (WristOx2® 3150, Nonin, USA) were used to estimate and transmit continuous Heart Rate (HR), Respiratory Rate (RR), and peripheral blood Oxygen Saturation (SpO2) data from ambulatory patients on these isolation wards to nurse bays remote from these patients, with a view to minimising the risk of infection for nursing staff. Our virtual High-Dependency Unit (vHDU) system used a secure web-based architecture and protocols (HTTPS and encrypted WebSockets) to transmit the vital-sign data in real time from wireless Android tablet devices, operating as patient data collection devices by the bedside in the isolation rooms, into the clinician dashboard interface available remotely via any modern web-browser. Fault-tolerant software strategies were used to reconnect the wearables automatically, avoiding the need for nurses to enter the isolation ward to re-set the patient monitoring equipment. The remote dashboard also displayed the vital-sign observations recorded by the nurses, using a separate electronic observation system, allowing them to review both sources of vital-sign data in one integrated chart. System usage was found to follow the trend of the number of local COVID-19 infections during the first wave of the pandemic in the UK (March to June 2020), with almost half of the patients on the isolation ward monitored with wearables during the peak of hospital admissions in the local area. Patients were monitored for a median of 31.5 [8.8, 75.4] hours, representing 88.1 [62.5, 94.5]% of the median time they were registered in the system. This indicates the system was being used in the isolation ward during this period. An updated version of the system has now also been used throughout the second and third waves of the pandemic in the UK.
Genesis of the Heiyanshan Tungsten Skarn Deposit in the East Tianshan, NW China: Insights From Geology, Fluid Inclusion, Isotopic Geochemistry and Geochronology
Authors: Xue Dong , Deng Xiao-Hua , Bagas Leon , Chen Xu-An , Wu Yan-Shuang , Jiang Xiao
Published: September 2021

The eastern Tianshan Terrane is a highly prospective zone that contains several porphyry Cu–Mo, VMS Cu–Zn, magmatic Cu–Ni, epithermal and orogenic Au deposits. However, few attention has been paid to tungsten deposits. Of these, the source and evolution of the mineralising fluids related to the skarn W deposits are poorly understood. The Heiyanshan W deposit is hosted by metamorphosed clastic and carbonate beds in the Mesoproterozoic Jianshanzi Formation deposited on a continental margin tectonic setting. The Jianshanzi Formation is intruded by biotite monzogranite that yield weighted206Pb/238U age of 326.9 ± 1.6 Ma, which suggest that the Heiyanshan W deposit was formed in the Carboniferous. The mineralisation is hosted by a prograde hydrothermal altered zone represented by a garnet (–pyroxene) skarn, and retrograde skarn characterised by fine-grained scheelite. The paragenesis of the Heiyanshan mineralisation can be subdivided into prograde skarn stage, retrograde skarn stage, quartz-sulphide stage and quartz-calcite vein stage. The types of fluid inclusions recognised in the various minerals in the deposits are liquid-rich aqueous, vapour-rich aqueous, and daughter mineral-bearing. The homogenisation temperatures of fluid inclusions from the Heiyanshan deposit decrease from 290 ± 28°C in garnet, through 232 ± 31°C in scheelite, to 232 ± 36°C in quartz and 158 ± 15°C in non-mineralised calcite, which is typical of W-bearing skarn deposits worldwide. The δ18Owatervalues from the Heiyanshan deposit range from +4.7 to +6.6‰ in garnet, +1.3 to +1.9‰ in quartz and −6.1 to −4.4‰ in calcite. We have measured δD in fluid inclusions from different minerals, although these bulk analyses are just a mixture of the different FIA’s present in the sample. The δD values of fluid inclusions in garnet, quartz, and calcite are from −121 to −71‰, −84 to −75‰ and −101 to −82‰, respectively, also indicative of deep-sourced magmatic fluids mixed with meteoric water. The decrease in the homogenisation temperatures for the fluid inclusions at the Heiyanshan deposit is accompanied by a drop in salinity indicating that tungsten-bearing minerals precipitated during fluid mixing between magmatic fluids and meteoric water. We conclude that eastern Tianshan Terrane contains two pulse of tungsten metallogenic events of Late Carboniferous and Early Triassic.
Continuous Blood Glucose Monitoring Increases Vigorous Physical Activity Levels and Is Associated With Reduced Hypoglycemia Avoidance Behavior In Youth With Type 1 Diabetes
Authors: Jabbour Georges , Bragazzi Nicola Luigi
Published: September 2021

The primary goal of this study was to explore physical activity (PA) levels, hypoglycemia fear scores and hypoglycemia episodes according to insulin administration and blood glucose monitoring methods in youth with type 1 diabetes (T1D). A self-administered questionnaire was completed by 28 children and 33 adolescents with T1D, and their PA was assessed. Hypoglycemia episodes, fear of hypoglycemia scores, insulin therapy (pump vs. injection) and blood glucose monitoring (continuous blood glucose monitors [CGMs] vs. blood glucose meters) methods are reported in the present work. There were no significant differences in the number of hypoglycemic episodes, child hypoglycemia fear survey behavior or total scores, or any components of the PA profile between youth using injections and those using a pump. However, these variables differed significantly when compared according to blood glucose monitoring method (CGMs vs. blood glucose meters): 41.2 vs. 81.8, p<0.01; 1.03 ± 0.05 vs. 2.6 ± 0.63, p<0.01; 1.09 ± 0.43 vs. 2.94 ± 0.22, p<0.01; and 222 ± 18 vs. 49 ± 11, p<0.01 (for total time in vigorous PA in minutes per week), respectively. CGM use correlated significantly with VPA levels (β=0.6; p=0.04). Higher VPA levels were associated with higher child hypoglycemia fear survey behavior scores (β=0.52; p=0.04). The latter correlates negatively with the number of episodes of hypoglycemia in the past 12 months in all category groups. The type of insulin injection was not associated with more activity in youth with T1D. In contrast, CGM use may be associated with increased vigorous PA among T1D youth. Those with higher hypoglycemia fear survey behavior scores engaged in more VPA and had fewer hypoglycemia episodes. Although CGM use ensures continuous monitoring of glycemia during exercise, increasing hypoglycemia avoidance behavior is still a necessary part of exercise management strategies in active youth with T1D.
Research on Efficient Soft Switching Based on MPPT of PV Power Generation System
Authors: Tao Peng , Cui Yan , Liang Jiayuan
Published: September 2021

In this paper, basic soft-switching technology is proposed based on hard switching, and then the basic soft-switching technology is optimized, and an improved soft-switching technology is proposed to improve the conversion efficiency by reducing the switching loss. The simulation results show that the conversion efficiency of hard and basic soft switching is 94.3 and 96.1%, but the conversion efficiency of improved soft switching optimized on the basis of basic soft switching is only 95.8%. To solve this problem, an innovative soft-switching technology is put forward in this paper, and its conversion efficiency is as high as 96.3%, which is superior to the basic soft-switching technology.
Strategies to Produce Cost-Effective Third-Generation Biofuel From Microalgae
Authors: Rafa Nazifa , Ahmed Shams Forruque , Badruddin Irfan Anjum , Mofijur M. , Kamangar Sarfaraz
Published: September 2021

Third-generation biofuel produced from microalgae is a viable solution to global energy insecurity and climate change. Despite an annual current global algal biomass production of 38 million litres, commercialization confronts significant economic challenges. However, cost minimization strategies, particularly for microalgae cultivation, have largely been excluded from recent studies. Therefore, this review provides essential insights into the technologies and economics of cost minimization strategies for large-scale applications. Cultivation of microalgae through aquafarming, in wastewater, or for biogas upgrading, and co-production of value-added products (VAPs) such as photo-bioreactors, protein, astaxanthin, and exopolysaccharides can drastically reduce biodiesel production costs. For instance, the co-production of photo-bioreactors and astaxanthin can reduce the cost of biodiesel production from $3.90 to $0.54 per litre. Though many technical challenges need to be addressed, the economic analysis reveals that incorporating such cost-effective strategies can make the biorefinery concept feasible and profitable. The cost of producing microalgal biodiesel can be lowered to $0.73kg−1dry weight when cultivated in wastewater or $0.54L−1when co-produced with VAPs. Most importantly, access to co-product markets with higher VAPs needs to be encouraged as the global market for microalgae-based VAPs is estimated to rise to $53.43 billion in 2026. Therefore, policies that incentivize research and development, as well as the production and consumption of microalgae-based biodiesel, are important to reduce the large gap in production cost that persists between biodiesel and petroleum diesel.
Genome-Wide Investigation of SBT Family Genes in Pineapple and Functional Analysis of AcoSBT1.12 in Floral Transition
Authors: Jin Xingyue , Liu Yanhui , Hou Zhimin , Zhang Yunfei , Fang Yunying , Huang Youmei , Cai Hanyang , Qin Yuan , Cheng Yan
Published: September 2021

SBT (Subtilisin-like serine protease), a clan of serine proteolytic enzymes, plays a versatile role in plant growth and defense. Although SBT family genes have been obtained from studies of dicots such as Arabidopsis, little is known about the potential functions of SBT in the monocots. In this study, 54 pineapple SBT genes (AcoSBTs) were divided into six subfamilies and then identified to be experienced strong purifying selective pressure and distributed on 25 chromosomes unevenly. Cis-acting element analysis indicated that almost all AcoSBTs promoters contain light-responsive elements. Further, the expression pattern via RNA-seq data showed that different AcoSBTs were preferentially expressed in different above-ground tissues. Transient expression in tobacco showed that AcoSBT1.12 was located in the plasma membrane. Moreover, Transgenic Arabidopsis ectopically overexpressing AcoSBT1.12 exhibited delayed flowering time. In addition, under the guidance of bioinformatic prediction, we found that AcoSBT1.12 could interact with AcoCWF19L, AcoPUF2, AcoCwfJL, Aco012905, and AcoSZF1 by yeast-two hybrid (Y2H). In summary, this study provided valuable information on pineapple SBT genes and illuminated the biological function of AcoSBT1.12 in floral transition.
Simulating CXCR5 Dynamics in Complex Tissue Microenvironments
Authors: Cosgrove Jason , Alden Kieran , Stein Jens V. , Coles Mark C. , Timmis Jon
Published: September 2021

To effectively navigate complex tissue microenvironments, immune cells sense molecular concentration gradients using G-protein coupled receptors. However, due to the complexity of receptor activity, and the multimodal nature of chemokine gradients in vivo, chemokine receptor activity in situ is poorly understood. To address this issue, we apply a modelling and simulation approach that permits analysis of the spatiotemporal dynamics of CXCR5 expression within an in silico B-follicle with single-cell resolution. Using this approach, we show that that in silico B-cell scanning is robust to changes in receptor numbers and changes in individual kinetic rates of receptor activity, but sensitive to global perturbations where multiple parameters are altered simultaneously. Through multi-objective optimization analysis we find that the rapid modulation of CXCR5 activity through receptor binding, desensitization and recycling is required for optimal antigen scanning rates. From these analyses we predict that chemokine receptor signaling dynamics regulate migration in complex tissue microenvironments to a greater extent than the total numbers of receptors on the cell surface.
Literature Mining and Mechanistic Graphical Modelling to Improve mRNA Vaccine Platforms
Authors: Leonardelli Lorena , Lofano Giuseppe , Selvaggio Gianluca , Parolo Silvia , Giampiccolo Stefano , Tomasoni Danilo , Domenici Enrico , Priami Corrado , Song Haifeng , Medini Duccio , Marchetti Luca , Siena Emilio
Published: September 2021

RNA vaccines represent a milestone in the history of vaccinology. They provide several advantages over more traditional approaches to vaccine development, showing strong immunogenicity and an overall favorable safety profile. While preclinical testing has provided some key insights on how RNA vaccines interact with the innate immune system, their mechanism of action appears to be fragmented amid the literature, making it difficult to formulate new hypotheses to be tested in clinical settings and ultimately improve this technology platform. Here, we propose a systems biology approach, based on the combination of literature mining and mechanistic graphical modeling, to consolidate existing knowledge around mRNA vaccines mode of action and enhance the translatability of preclinical hypotheses into clinical evidence. A Natural Language Processing (NLP) pipeline for automated knowledge extraction retrieved key biological evidences that were joined into an interactive mechanistic graphical model representing the chain of immune events induced by mRNA vaccines administration. The achieved mechanistic graphical model will help the design of future experiments, foster the generation of new hypotheses and set the basis for the development of mathematical models capable of simulating and predicting the immune response to mRNA vaccines.
Integrated Analysis of Prognostic Genes Associated With Ischemia–Reperfusion Injury in Renal Transplantation
Authors: Zhang Di , Wang Yicun , Zeng Song , Zhang Min , Zhang Xin , Wang Yuxuan , Zhang Zijian , Wang Xi , Hu Xiaopeng
Published: September 2021

Background

Ischemia–reperfusion injury (IRI) remains an inevitable and major challenge in renal transplantation. The current study aims to obtain deep insights into underlying mechanisms and seek prognostic genes as potential therapeutic targets for renal IRI (RIRI).

Methods

After systematically screening the Gene Expression Omnibus (GEO) database, we collected gene expression profiles of over 1,000 specimens from 11 independent cohorts. Differentially expressed genes (DEGs) were identified by comparing allograft kidney biopsies taken before and after reperfusion in the discovery cohort and further validated in another two independent transplant cohorts. Then, graft survival analysis and immune cell analysis of DEGs were performed in another independent renal transplant cohort with long-term follow-ups to further screen out prognostic genes. Cell type and time course analyses were performed for investigating the expression pattern of prognostic genes in more dimensions utilizing a mouse RIRI model. Finally, two novel genes firstly identified in RIRI were verified in the mouse model and comprehensively analyzed to investigate potential mechanisms.

Results

Twenty DEGs upregulated in the process of RIRI throughout different donor types (living donors, cardiac and brain death donors) were successfully identified and validated. Among them, upregulation of 10 genes was associated with poor long-term allograft outcomes and exhibited strong correlations with prognostic immune cells, like macrophages. Furthermore, certain genes were found to be only differentially expressed in specific cell types and remained with high expression levels even months after RIRI in the mouse model, which processed the potential to serve as therapeutic targets. Importantly, two newly identified genes in RIRI, Btg2 and Rhob, were successfully confirmed in the mouse model and found to have strong connections with NF-κB signaling.

Conclusions

We successfully identified and validated 10 IRI-associated prognostic genes in renal transplantation across different donor types, and two novel genes with crucial roles in RIRI were recognized for the first time. Our findings offered promising potential therapeutic targets for RIRI in renal transplantation.
Early Life-History Dynamics of Caribbean Octocorals: The Critical Role of Larval Supply and Partial Mortality
Authors: Martínez-Quintana Ángela , Lasker Howard R.
Published: September 2021

Recruitment is a key demographic process for maintenance of local populations and recovery following disturbance. For marine invertebrates, distribution and abundances of recruits are impacted by spatiotemporal variation in larval supply, settlement rates and post-settlement survival. However, for colonial and modular organisms, differences in survival and growth between settlers and colonial recruits may also affect recruitment patterns. In the Caribbean, shifts in the benthic community structure favoring octocoral’s have been detected, and recruitment has been suggested as key for octocoral’s resilience. Hence, we studied octocoral recruitment dynamics, and evaluated the role of pre-settlement, settlement and post-settlement processes in recruit’s densities. We performed the study at two sites with different octocoral densities, on the south coast of St. John, United States Virgin Islands, and distinguished between processes occurring to recently settled polyps and to colonial recruits. At both sites, we monitoredP. homomallasettlers on settlement tiles for 3 months, and colonial recruits of two of the most abundant genera (EuniceaandPseudoplexaura)for 3 years. In addition, we assessed whether recruits morphological traits affected recruitment and divided recruits of the genusEuniceabased on the presence of large calyces. The major contributor to both, single-polyps and colonial recruit densities was larval supply. Single-polyp densities were not limited by the availability of space, settlement cues, or early post-settlement survival. Height was the only predictor of survival and growth of colonial recruits, with potential growth rates increasing with height. However, large recruits suffered partial mortality often, distorting the relationship between recruit age and size, and causing most recruits to remain in the recruit size class (≤5 cm) longer than a year. Octocorals have been resilient to the conditions that have driven the decline of scleractinian corals throughout the Caribbean, and recruitment has been key to that success. Our results are crucial to understand early life history dynamics of Caribbean octocorals, and highlights the need to standardize the definition of recruit among colonial and modular taxa to facilitate inter-specific comparisons, and to understand future changes in coral reef community assemblages.
Developing a Precautionary Management Approach for the Eastern Canada-West Greenland Population of Bowhead Whales (Balaena mysticetus)
Authors: Ferguson Steven H. , Higdon Jeff W. , Hall Patricia A. , Hansen Rikke Guldborg , Doniol-Valcroze Thomas
Published: September 2021

Bowhead whales (Balaena mysticetusL., 1758) of the Eastern Canada-West Greenland population have been hunted by Inuit for millennia. Significant commercial harvests, conducted by European and American whalers for about 400 years, ended ca. 1915. A small co-managed subsistence harvest from this population has occurred inconsistently in Canada and Greenland, since 1996 and 2009, respectively. Since near extirpation from commercial whaling, population size has increased and the Inuit subsistence hunt now requires a harvest management framework that incorporates knowledge of abundance trends, population dynamics, and carrying capacity. Here, we use a model estimate of pre-commercial exploitation abundance to approximate carrying capacity and develop a management framework with reference points and corresponding stock status zones. When applied to recent abundance estimates, our framework indicates that the population is likely within the healthy (N50–N70) zone. Thus, an appropriate management objective is to support continued population increase, with concurrent marginal harvesting, while maintaining the population level above the target reference point (N70) of ca 12,000 whales. However, there remains large uncertainty about current population size and growth rate. The resulting data gaps require a plan for future research to monitor this population in the context of climate changes.
Leveraging the Interdependencies Between Barrier Islands and Backbarrier Saltmarshes to Enhance Resilience to Sea-Level Rise
Authors: Hein Christopher J. , Fenster Michael S. , Gedan Keryn B. , Tabar Jeff R. , Hein Emily A. , DeMunda Todd
Published: September 2021

Barrier islands and their backbarrier saltmarshes have a reciprocal relationship: aeolian and storm processes transport sediment from the beaches and dunes to create and build marshes along the landward fringe of the island. In turn, these marshes exert a stabilizing influence on the barrier by widening the barrier system and forming a platform onto which the island migrates, consequently slowing landward barrier migration and inhibiting storm breaching. Here, we present a novel framework for applying these natural interdependencies to managing coastal systems and enhancing barrier-island resilience. Further, we detail application of these principles through a case study of the design of a marsh creation project that showcases the interdisciplinary engagement of scientists, engineers, stakeholders, and policymakers. Specifically, we describe: (1) the ecologic, sedimentologic, stratigraphic, and morphologic data obtained from the southern 4 km of Cedar Island (Virginia, United States) and nearby backbarrier tidal channels, tidal flats, and flood-tidal deltas, and (2) the use of those data to develop an engineering and design plan for the construction of a high (46 ha) and low (42 ha) fringing marsh platform located behind the island, proximal to a former ephemeral inlet. Additionally, we chronicle the process used to narrow five initial alternative designs to the optimal final plan. This process involved balancing best-available existing science and models, considering design and financial constraints, identifying stakeholder preferences, and maximizing restoration benefits of habitat provision and shoreline protection. Construction of this marsh would: (1) provide additional habitat and ecosystem benefits, (2) slow the rapid migration (up to 15 m/yr at present) of the barrier island, and (3) hinder island breaching. Ultimately, this project – presently at the final design and permitting stage – may enhance the storm and sea-level rise resilience of the island, backbarrier marshes and lagoons, and the mainland town community; and provide an example of a novel science-based approach to coastal resilience that could be applied to other global barrier settings.
Longitudinal Characterization of Cytokine Overproduction: A Case Report in Critically Ill COVID-19 Patients With Hyperinflammation in Bronchoalveolar Lavage
Authors: Luo Zhen , Zhu Chengliang , Ruan Zhihui , Cui Xianghua , Shereen Muhammad Adnan , Pan Pan , Huang Jingtao , Wang Fubing , Su Hanwen , Xia Yuchen , Wu Jianguo
Published: September 2021

Objectives: The longitudinal characterization and risk of poor outcomes related to cytokine overproduction in critical coronavirus disease 2019 (COVID-19) patients with hyperinflammation in bronchoalveolar lavage requires further investigation.

Methods: We enrolled two critically ill patients with comorbidities diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detected by RT-PCR during hospitalization. Clinical characteristics, longitudinal immunological, and biochemical parameters of each critical COVID-19 case were collected.

Main Results: The clinical characteristics and laboratory results of each case demonstrated critical symptoms of COVID-19 with poor outcomes. Both nasopharyngeal swabs and bronchoalveolar lavage fluid (BALF) samples tested positive for SARS-CoV-2. Two patients received targeted treatments against pathogen infection and inflammation in addition to interventional therapies, except for Patient 2, who received an additional artificial liver system treatment. Hyperinflammation with a dominantly high level of IL-6 was observed in BALF samples from both critical cases with decreased T cell populations. High levels of cytokines and pathological parameters were successively maintained in Patient 1, but rapidly reduced at the late treatment stage in Patient 2. The outcome of Patient 1 is death, whereas the outcome of Patient 2 is recovery.

Conclusions: This case report suggests that a high risk of poor outcomes was related to a heavily hyperinflammatory milieu in both the blood and lungs of critical COVID-19 patients. The artificial liver intervention on cytokines overproduction might be beneficial for the recovery of critical COVID-19 patients as a reliable therapy that can be coordinated with targeted treatments, which ought to be further tested in adequately designed and powered clinical trials.
Contrasting Vaginal Bacterial Communities Between Estrus and Non-estrus of Giant Pandas (Ailuropoda melanoleuca)
Authors: Yue Chanjuan , Luo Xue , Ma Xiaoping , Zhang Dongsheng , Yan Xia , Deng Zeshuai , Li Yunli , Liu Yuliang , An Junhui , Fan Xueyang , Li Lin , Su Xiaoyan , Hou Rong , Cao Suizhong , Liu Songrui
Published: September 2021

Bacterial infection and imbalance of bacterial community in the genitourinary system of giant panda could affect the reproductive health. In severe cases, it can also lead to abortion. In this study, 13 of vaginal secretions in the estrue (E) group and seven of vaginal secretions in the non-estrue (NE) group were used to study the composition and diversity of vaginal bacterial communities between estrus and non-estrus by 16S rRNA gene sequencing analysis. The results showed that the vaginal microbiome in giant pandas shared the same top five abundant species between estrus and non-estrus at the phylum level. However, the vaginal microbiome changed significantly during estrus at the genus level. In top 10 genera, the abundance of Escherichia, Streptococcus, and Bacteroides in the E group was significantly higher than that in the NE group (p<0.05); Azomonas, Porphyromonas, Prevotella, Campylobacter, and Peptoniphilus in the NE group was significantly higher than that in the E group (p<0.05). The richness and diversity of vaginal microbiome in giant panda on estrus were significantly lower than those on non-estrus (p<0.05). It is noteworthy that the abundance of Streptococcus, Escherichia, and Bacteroides of vagina in giant pandas maintained low abundance in the daily. Whereas, they increased significantly during estrus period, which may play an important role in female giant pandas during estrus period. It was hypothesized that hormones may be responsible for the changes in the vaginal microbiome of giant pandas between estrus and no-estrus stages.
Systematic Analysis of the Impact of R-Methylation on RBPs-RNA Interactions: A Proteomic Approach
Authors: Maniaci Marianna , Boffo Francesca Ludovica , Massignani Enrico , Bonaldi Tiziana
Published: September 2021

RNA binding proteins (RBPs) bind RNAs through specific RNA-binding domains, generating multi-molecular complexes known as ribonucleoproteins (RNPs). Various post-translational modifications (PTMs) have been described to regulate RBP structure, subcellular localization, and interactions with other proteins or RNAs. Recent proteome-wide experiments showed that RBPs are the most representative group within the class of arginine (R)-methylated proteins. Moreover, emerging evidence suggests that this modification plays a role in the regulation of RBP-RNA interactions. Nevertheless, a systematic analysis of how changes in protein-R-methylation can affect globally RBPs-RNA interactions is still missing. We describe here a quantitative proteomics approach to profile global changes of RBP-RNA interactions upon the modulation of type I and II protein arginine methyltransferases (PRMTs). By coupling the recently described Orthogonal Organic Phase Separation (OOPS) strategy with the Stable Isotope Labelling with Amino acids in Cell culture (SILAC) and pharmacological modulation of PRMTs, we profiled RNA-protein interaction dynamics in dependence of protein-R-methylation. Data are available via ProteomeXchange with identifier PXD024601.
Altered Brain Functional Network in Subtypes of Parkinson's Disease: A Dynamic Perspective
Authors: Zhu Junlan , Zeng Qiaoling , Shi Qiao , Li Jiao , Dong Shuwen , Lai Chao , Cheng Guanxun
Published: September 2021

Background: Parkinson's disease (PD) is a highly heterogeneous disease, especially in the clinical characteristics and prognosis. The PD is divided into two subgroups: tremor-dominant phenotype and non-tremor-dominant phenotype. Previous studies reported abnormal changes between the two PD phenotypes by using the static functional connectivity analysis. However, the dynamic properties of brain networks between the two PD phenotypes are not yet clear. Therefore, we aimed to uncover the dynamic functional network connectivity (dFNC) between the two PD phenotypes at the subnetwork level, focusing on the temporal properties of dFNC and the variability of network efficiency.

Methods: We investigated the resting-state functional MRI (fMRI) data from 29 tremor-dominant PD patients (PDTD), 25 non-tremor-dominant PD patients (PDNTD), and 20 healthy controls (HCs). Sliding window approach, k-means clustering, independent component analysis (ICA), and graph theory analysis were applied to analyze the dFNC. Furthermore, the relationship between alterations in the dynamic properties and clinical features was assessed.

Results: The dFNC analyses identified four reoccurring states, one of them showing sparse connections (state I). PDTD patients stayed longer time in state I and showed increased FNC between BG and vSMN in state IV. Both PD phenotypes exhibited higher FNC between dSMN and FPN in state II and state III compared with the controls. PDNTD patients showed decreased FNC between BG and FPN but increased FNC in the bilateral FPN compared with both PDTD patients and controls. In addition, PDNTD patients exhibited greater variability in global network efficiency. Tremor scores were positively correlated with dwell time in state I along with increased FNC between BG and vSMN in state IV.

Conclusions: This study explores the dFNC between the PDTD and PDNTD patients, which offers new evidence on the abnormal time-varying brain functional connectivity and their network destruction of the two PD phenotypes, and may help better understand the neural substrates underlying different types of PD.
Mitochondrial Dynamics: A Potential Therapeutic Target for Ischemic Stroke
Authors: Zhou Xiangyue , Chen Hanmin , Wang Ling , Lenahan Cameron , Lian Lifei , Ou Yibo , He Yue
Published: September 2021

Stroke is one of the leading causes of death and disability worldwide. Brain injury after ischemic stroke involves multiple pathophysiological mechanisms, such as oxidative stress, mitochondrial dysfunction, excitotoxicity, calcium overload, neuroinflammation, neuronal apoptosis, and blood-brain barrier (BBB) disruption. All of these factors are associated with dysfunctional energy metabolism after stroke. Mitochondria are organelles that provide adenosine triphosphate (ATP) to the cell through oxidative phosphorylation. Mitochondrial dynamics means that the mitochondria are constantly changing and that they maintain the normal physiological functions of the cell through continuous division and fusion. Mitochondrial dynamics are closely associated with various pathophysiological mechanisms of post-stroke brain injury. In this review, we will discuss the role of the molecular mechanisms of mitochondrial dynamics in energy metabolism after ischemic stroke, as well as new strategies to restore energy homeostasis and neural function. Through this, we hope to uncover new therapeutic targets for the treatment of ischemic stroke.
Filipino Multicomponent Intervention to Maintain Cognitive Performance in High-Risk Population (FINOMAIN): Study Protocol for a Cluster Randomized Controlled Trial
Authors: Dominguez Jacqueline , de Guzman Ma. Fe , Chen S. H. Annabel , Sano Mary , Waldemar Gunhild , Phung Thien Kieu Thi
Published: September 2021

Background: More than half of the people with dementia live in lower-middle income countries (LMIC), yet we lack research and evidence-based knowledge to guide health promotion and prevention strategies for cognitive decline. In the Philippines, the prevalence of mild cognitive impairment (MCI) and cardiovascular risk factors among older persons are high, making this population at high risk for developing dementia. This protocol describes a cluster randomized controlled trial that aims to investigate the efficacy of a multicomponent intervention to maintain cognitive performance among high-risk population.

Methods: This is a cluster-randomized, two-arm, single-blind trial of a multicomponent intervention that combines dance called INDAK (Improving Neurocognition through Dance and Kinesthetics), nutrition counseling, and vascular risk management. The intervention arm will receive 12 months (1-h, twice per week) of INDAK and every 3 months of nutrition counseling and intensive vascular risk management and monitoring. The control group will receive the usual vascular care advice and referral. A total of 605 (20–25 clusters per arm) community-dwelling Filipino older adults aged ≥ 60 years old with MCI will participate in the study and will be assessed at baseline, 6th- and 12th-month follow-up. The primary outcome is cognitive performance assessed by the Alzheimer's Disease Assessment Scale—Cognitive (ADAS-Cog), Mnemonic Similarity Tasks (MST), and executive function composite (EFC). Secondary outcomes are functional connectivity assessed through brain imaging, and measures of behavioral, functional level, and quality of life.

Discussion: The study aims to provide scientific evidence on a public health intervention that is contextualized in a community setting to reduce dementia risk among older adults with MCI. This model can be an ecological, low-cost, and effective program, thereby conducive to widespread implementation in the Philippines as well as in other low-resource settings with similar public health challenges. The pilot phase was underway with eight villages (clusters), but temporarily interrupted by the pandemic. The full study is anticipated to start after community restrictions are eased.
Recommendations for the Development of Socioeconomically-Situated and Clinically-Relevant Neuroimaging Models of Pain
Authors: Reddan Marianne C.
Published: September 2021

Pain is a complex, multidimensional experience that emerges from interactions among sensory, affective, and cognitive processes in the brain. Neuroimaging allows us to identify these component processes and model how they combine to instantiate the pain experience. However, the clinical impact of pain neuroimaging models has been limited by inadequate population sampling – young healthy college students are not representative of chronic pain patients. The biopsychosocial approach to pain management situates a person's pain within the diverse socioeconomic environments they live in. To increase the clinical relevance of pain neuroimaging models, a three-fold biopsychosocial approach to neuroimaging biomarker development is recommended. The first level calls for the development of diagnostic biomarkers via the standard population-based (nomothetic) approach with an emphasis on diverse sampling. The second level calls for the development of treatment-relevant models via a constrained person-based (idiographic) approach tailored to unique individuals. The third level calls for the development of prevention-relevant models via a novel society-based (social epidemiologic) approach that combines survey and neuroimaging data to predict chronic pain risk based on one's socioeconomic conditions. The recommendations in this article address how we can leverage pain's complexity in service of the patient and society by modeling not just individuals and populations, but also the socioeconomic structures that shape any individual's expectations of threat, safety, and resource availability.
Treatment Challenges in Acute Minor Ischemic Stroke
Authors: Slawski Diana , Heit Jeremy J.
Published: September 2021

Patients with acute ischemic stroke may present with minor neurologic deficits. Acute treatment decisions depend on the disability imposed by the symptoms along with radiographic features. The presence of disabling neurologic deficits warrants intravenous thrombolysis, but the indications for endovascular therapy are less defined. The degree of disability, presence of a large vessel occlusion with perfusion mismatch, and collateral circulation status may all be factors in selecting patients for endovascular treatment. Identification of patients who are at risk for neurologic deterioration is critical to preventing poor outcomes in this patient population.
Case Report: Anterior Spinal Cord Ischemia Following Embolization of Cerebellar Arteriovenous Malformation: An Illustrative Case and Review of Spinal Cord Vascular Anatomy
Authors: Moazeni Yasaman , Cantrell Donald R. , Clark Jeffrey R. , Abdalla Ramez N. , Batra Ayush , Hurley Michael C. , Ansari Sameer A. , Russell Eric J. , Shaibani Ali
Published: September 2021

Spinal cord ischemia (SCI) is a rare entity with high mortality and morbidity which can arise from causes such as atherosclerosis, aortic dissection or aneurysm, thromboembolic events or systemic hypotension, and is a potential complication of spinal surgery. Published literature contains very few reports of SCI as a complication of intracranial interventions, highlighting the uncommon nature of SCI in these circumstances. We report the occurrence of anterior SCI in a 69-year-old patient following successful embolization of a cerebellar arteriovenous malformation (AVM), marked by upper extremity weakness, lower extremity paraplegia, loss of bladder and bowel control, and hypercapnic respiratory failure requiring mechanical ventilation. Magnetic resonance imaging (MRI) demonstrated upper cervical diffusion restriction and T2/STIR hyperintensity. Unusually, SCI occurred in this case without intraprocedural catheter wedging or obvious flow limitation, prolonged procedure time, hypercoagulable state, or general hypotension. We review previous cases in the literature as well as spinal cord vascular anatomy, and discuss the possible etiologies of this complication. Spinal cord ischemia could be a very rare complication of neuroendovascular procedures even in the absence of warning signs and should be carefully evaluated in patients with suspected neurologic symptoms after such procedures.
Effect of Restricted Feeding on Metabolic Health and Sleep-Wake Rhythms in Aging Mice
Authors: Xu Yong-Xia , Liu Guo-Ying , Jiang Qian , Bi Han-Qi , Wang Shi-Chan , Zhang Ping-Ping , Gao Chao-Bing , Chen Gui-Hai , Cheng Wen-Hui , Chen Guan-Jun , Zhu De-Fa , Zhong Ming-Kui , Xu Qi
Published: September 2021

Aging, an irreversible and unavoidable physiological process in all organisms, is often accompanied by obesity, diabetes, cardiovascular diseases, sleep disorders, and fatigue. Thus, older adults are more likely to experience metabolic symptoms and sleep disturbances than are younger adults. Restricted feeding (RF) is a dietary regimen aimed at improving metabolic health and extending longevity, as well as reorganizing sleep-wake cycles. However, the potential of RF to improve metabolic health and sleep quality in older adults who are known to show a tendency toward increased weight gain and decreased sleep is unknown. To elucidate this issue, aged mice were assigned to an RF protocol during the active phase for 2 h per day for 2 weeks. Sleep-wake cycles were recorded during the RF regime in RF group and control mice. At the end of this period, body weight and blood biochemistry profiles, including blood glucose, cholesterol, and enzyme activity, in addition to dopamine concentrations in the brain, were measured in the RF group and age-matched controls. RF for 2 weeks improved the metabolic health of aged mice by reducing their body weights and blood glucose and cholesterol levels. At the beginning of the RF regime, sleep decreased in the dark period but not in the light period. After stable food entrainment was achieved (7 days post-RF commencement), the amount of time spent in wakefulness during the light period dramatically increased for 2 h before food availability, thereby increasing the mean duration of awake episodes and decreasing the number of wakefulness episodes. There was no significant difference in the sleep-wake time during the dark period in the RF group, with similar total amounts of wakefulness and sleep in a 24-h period to those of the controls. During the RF regime, dopamine levels in the midbrain increased in the RF group, pointing to its potential as the mechanism mediating metabolic symptoms and sleep-wake regulation during RF. In conclusion, our study suggested that RF during aging might prohibit or delay the onset of age-related diseases by improving metabolic health, without having a severe deleterious effect on sleep.
Immunomodulatory Role of Nutrients: How Can Pulmonary Dysfunctions Improve?
Authors: Gozzi-Silva Sarah Cristina , Teixeira Franciane Mouradian Emidio , Duarte Alberto José da Silva , Sato Maria Notomi , Oliveira Luana de Mendonça
Published: September 2021

Nutrition is an important tool that can be used to modulate the immune response during infectious diseases. In addition, through diet, important substrates are acquired for the biosynthesis of regulatory molecules in the immune response, influencing the progression and treatment of chronic lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD). In this way, nutrition can promote lung health status. A range of nutrients, such as vitamins (A, C, D, and E), minerals (zinc, selenium, iron, and magnesium), flavonoids and fatty acids, play important roles in reducing the risk of pulmonary chronic diseases and viral infections. Through their antioxidant and anti-inflammatory effects, nutrients are associated with better lung function and a lower risk of complications since they can decrease the harmful effects from the immune system during the inflammatory response. In addition, bioactive compounds can even contribute to epigenetic changes, including histone deacetylase (HDAC) modifications that inhibit the transcription of proinflammatory cytokines, which can contribute to the maintenance of homeostasis in the context of infections and chronic inflammatory diseases. These nutrients also play an important role in activating immune responses against pathogens, which can help the immune system during infections. Here, we provide an updated overview of the roles played by dietary factors and how they can affect respiratory health. Therefore, we will show the anti-inflammatory role of flavonoids, fatty acids, vitamins and microbiota, important for the control of chronic inflammatory diseases and allergies, in addition to the antiviral role of vitamins, flavonoids, and minerals during pulmonary viral infections, addressing the mechanisms involved in each function. These mechanisms are interesting in the discussion of perspectives associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its pulmonary complications since patients with severe disease have vitamins deficiency, especially vitamin D. In addition, researches with the use of flavonoids have been shown to decrease viral replicationin vitro. This way, a full understanding of dietary influences can improve the lung health of patients.
Epithelial-to-Mesenchymal Transition in Fibrosis: Concepts and Targeting Strategies
Authors: Lovisa Sara
Published: September 2021

The epithelial-to-mesenchymal transition (EMT), an embryonic program relaunched during wound healing and in pathological conditions such as fibrosis and cancer, continues to gain the attention of the research community, as testified by the exponential trend of publications since its discovery in the seventies. From the first description as a mesenchymal transformation, the concept of EMT has been substantially refined as an in-depth comprehension of its functional role has recently emerged thanks to the implementation of novel mouse models as well as the use of sophisticated mathematical modeling and bioinformatic analysis. Nevertheless, attempts to targeting EMT in fibrotic diseases are at their infancy and continue to pose several challenges. The aim of this mini review is to recapitulate the most recent concepts in the EMT field and to summarize the different strategies which have been exploited to target EMT in fibrotic disorders.
Qingchang Wenzhong Decoction Accelerates Intestinal Mucosal Healing Through Modulation of Dysregulated Gut Microbiome, Intestinal Barrier and Immune Responses in Mice
Authors: Sun Zhongmei , Li Junxiang , Wang Wenting , Liu Yuyue , Liu Jia , Jiang Hui , Lu Qiongqiong , Ding Panghua , Shi Rui , Zhao Xingjie , Yuan Wenjing , Tan Xiang , Shi Xiaojun , Xing Yunqi , Mao Tangyou
Published: September 2021

Inflammatory bowel disease (IBD), a group of multifactorial and inflammatory infirmities, is closely associated with dysregulation of gut microbiota and host metabolome, but effective treatments are currently limited. Qingchang Wenzhong Decoction (QCWZD) is an effective and classical traditional herbal prescription for the treatment of IBD and has been proved to attenuate intestinal inflammation in a model of acute colitis. However, the role of QCWZD in recovery phase of colitis is unclear. Here, we demonstrated that mice treated with QCWZD showed a faster recovery from dextran sulfate sodium (DSS)-induced epithelial injury, accompanied by reduced mucosal inflammation and attenuated intestinal dysbiosis using bacterial 16S rRNA amplicon sequencing compared to those receiving sterile water. The protective effects of QCWZD are gut microbiota dependent, as demonstrated by fecal microbiome transplantation and antibiotics treatment. Gut microbes transferred from QCWZD-treated mice displayed a similar role in mucosal protection and epithelial regeneration as QCWZD on colitis in mice, and depletion of the gut microbiota through antibiotics treatments diminished the beneficial effects of QCWZD on colitis mice. Moreover, metabolomic analysis revealed metabolic profiles alternations in response to the gut microbiota reprogrammed by QCWZD intervention, especially enhanced tryptophan metabolism, which may further accelerate intestinal stem cells-mediated epithelial regeneration to protect the integrity of intestinal mucosa through activation of Wnt/β-catenin signals. Collectively, our results suggested that orally administrated QCWZD accelerates intestinal mucosal healing through the modulation of dysregulated gut microbiota and metabolism, thus regulating intestinal stem cells-mediated epithelial proliferation, and hold promise for novel microbial-based therapies in the treatment of IBD.