bluuebunny/crossref_metadata_2025 huggingface dataset:
“We Need to be Better”: Race, Outdoor Recreation, and Corporate Social Advocacy
Authors: Tarin Carlos Anthony , Upton Sarah De Los Santos , Hernández Leandra Hinojosa
Published: December 2021

The summer 2020 protests following the killings of George Floyd, Breonna Taylor, Ahmaud Arbery, and other African-Americans sparked important conversations about race, police brutality, and institutionalized racism in the United States. In response to widespread civil unrest, organizations across the country issued statements condemning anti-Black violence and supporting the Black Lives Matter movement. This essay analyzes public statements released by 50 outdoor sport and recreation organizations. Extending scholarly literature on race and corporate social advocacy, our analysis develops the concept of conciliatory discourse, which functions by rhetorically constructing 1) a non-specification of grievance, 2) an obfuscation of commitments to action, and 3) a reinforcement of previous actions or processes. We argue that while many outdoor recreation organizations took action in support of racial justice, their public statements complicate long-term commitments for inclusivity and diversity.
Inflammatory Cells Accelerated Carotid Artery Calcification via MMP9: Evidences From Single-Cell Analysis
Authors: Liang Xiaobing , He Wanbing , Zhang Hua , Luo Dongling , Zhang Zhengzhipeng , Liu Aiting , Wang Jinkai , Huang Hui
Published: December 2021

Background: Vascular calcification (VC) is an important predictor of prognosis in atherosclerosis, the phenotypic transformation of vascular smooth muscle cells (VSMCs) is thought to be a process of VC. However, the implications and potential mechanisms for VSMCs phenotypic transition remain unknown.

Methods: To study the transformation of vascular smooth muscle cells (VSMCs) in the calcification early period, we analyzed single-cell sequencing data from carotid artery calcified core and paracellular tissue, based on the results of enrichment analysis and protein-protein interaction analysis. Upstream transcription factors were tracked and finally the results were validated using the MESA database.

Results: We successfully identified a subpopulation of inflammatory macrophage-like VSMCs and determined that MMP9 is an important factor in the phenotypic transformation of VSMCs. We found that RELA regulates MMP9 expression and that knockdown of RELA attenuated MMP9 expression and reduced the expression of BMP2 and the macrophage marker LGALS3 in vascular smooth muscle in inflammatory states, while serum levels of MMP9 correlated significantly with the inflammatory response.

Conclusion: This study reveals that the phenotypic transformation of VSMCs can be regulated by modulating MMP9, providing a new idea for the early treatment of VC.
Long-Term Outcomes of Peripheral Blood Mononuclear Cells in the Treatment of Angiitis-Induced No-Option Critical Limb-Threatening Ischemia
Authors: Jiang Xiaolang , Liu Hao , Pan Tianyue , Gu Shiyang , Fang Yuan , Wei Zheng , Fang Gang , Chen Bin , Jiang Junhao , Shi Yun , Liu Peng , Fu Weiguo , Dong Zhihui
Published: December 2021

Background: Peripheral blood mononuclear cells (PBMNCs) showed encouraging short outcomes in the treatment of angiitis-induced no-option critical limb-threatening ischemia (AICLTI) in the pilot study. This study aimed to demonstrate the long-term outcomes of this treatment.

Methods: From May 2014 to December 2018, patients diagnosed with AICLTI and treated by autotransplantation of PBMNCs in our center were enrolled and analyzed. The primary endpoint was major amputation-free survival (MAFS), the secondary endpoints included peak pain-free walking time (PPFWT), Wong-Baker FACES pain rating scale score (WFPRSS), labor recovery, ankle-brachial index (ABI), transcutaneous partial oxygen pressure (TcpO2), and SF-36v2 scores.

Results: A total of 58 patients were enrolled. During a minimal follow-up of 36 months, the MAFS was 93.1% and the labor competence restored rate was 62.1%. The WFPRSS was decreased from 8.7 ± 1.6 to 1.6 ± 3.2, and PPFWT was significantly improved from 2.9 ± 4.2 min to 16.6 ± 6.9 min. The quality of life was also significantly improved at each follow-up point. Perfusion evaluating parameters, such as ABI and TcPO2, were also significantly improved. No critical adverse event was observed during the treatment and follow-up period.

Conclusions: The treatment of AICLTI by autotransplantation of PBMNCs demonstrated encouraging long-term results. It could not only restore labor competence, improve the quality of life, but also significantly reduce the major amputation rate.
Mitochondrial Dynamics: Pathogenesis and Therapeutic Targets of Vascular Diseases
Authors: Luan Yi , Ren Kai-Di , Luan Ying , Chen Xing , Yang Yang
Published: December 2021

Vascular diseases, particularly atherosclerosis, are associated with high morbidity and mortality. Endothelial cell (EC) or vascular smooth muscle cell (VSMC) dysfunction leads to blood vessel abnormalities, which cause a series of vascular diseases. The mitochondria are the core sites of cell energy metabolism and function in blood vessel development and vascular disease pathogenesis. Mitochondrial dynamics, including fusion and fission, affect a variety of physiological or pathological processes. Multiple studies have confirmed the influence of mitochondrial dynamics on vascular diseases. This review discusses the regulatory mechanisms of mitochondrial dynamics, the key proteins that mediate mitochondrial fusion and fission, and their potential effects on ECs and VSMCs. We demonstrated the possibility of mitochondrial dynamics as a potential target for the treatment of vascular diseases.
Is Coronary Artery Ectasia a Progressive Disease? A Self-Controlled Retrospective Cohort Study
Authors: Liu Ruifeng , Zhao Huiqiang , Gao Xiangyu , Liang Siwen
Published: December 2021

Objective: It is essential to understand whether coronary artery ectasia (CAE) progresses over time because the patients might be under the risk of coronary rupture, and stent implant should be avoided if ectatic changes progress.

Methods: A consecutive series of 99 CAE patients who had undergone coronary angiography at least twice were enrolled and followed up for 1–16 years until they received a second angiogram. Subjects were divided into two groups (1–5 vs. 5–16 years of follow-up), then the basic clinical characteristics and coronary artery images were compared over time.

Results: (1) All CAE patients exhibited atherosclerosis, and a majority presented with acute myocardial infarction. Most baseline clinical characteristics were relatively stable. (2) Atherosclerosis (indicated by the distribution of stenosis in coronary vessels) and the Gensini scores progressed significantly. Ectasia extent showed minimal changes as indicated by blood vessel involvement, Markis type, coronary blood flow, ectasia diameter, and ectasia length. (3) Multilinear regression analysis revealed that the underlying factors related to stenosis evolution indicated by fold of Gensini score were: longer time interval, lower baseline Gensini score, and higher hypersensitive C-reactive protein concentration. (4) There was a relationship between the ectatic diameter and the extent of stenosis.

Conclusions: For CAE patients with atherosclerosis followed for 1–16 years, there was minimal CAE progression, while the atherosclerosis progressed and the ectasia extent was related to degree of stenosis. The results indicate that prevention and treatment of atherosclerotic changes might have more clinical significance than addressing ectatic changes.
Gas Emissions From the Western Aleutians Volcanic Arc
Authors: Fischer Tobias P. , Lopez Taryn M. , Aiuppa Alessandro , Rizzo Andrea L. , Ilanko Tehnuka , Kelley Katherine A. , Cottrell Elizabeth
Published: December 2021

The Aleutian Arc is remote and highly active volcanically. Its 4,000 km extent from mainland Alaska to Russia’s Kamchatka peninsula hosts over 140 volcanic centers of which about 50 have erupted in historic times. We present data of volcanic gas samples and gas emission measurements obtained during an expedition to the western-most segment of the arc in September 2015 in order to extend the sparse knowledge on volatile emissions from this remote but volcanically active region. Some of the volcanoes investigated here have not been sampled for gases before this writing. Our data show that all volcanoes host high-temperature magmatic-hydrothermal systems and have gas discharges typical of volcanoes in oceanic arcs. Based on helium isotopes, the western Aleutian Arc segment has minimal volatile contributions from the overriding crust. Volcanic CO2fluxes from this arc segment are small, compared to the emissions from volcanoes on the Alaska Peninsula and mainland Alaska. The comparatively low CO2emissions may be related to the lower sediment flux delivered to the trench in this part of the arc.
Metabolomic Profile of Skeletal Muscle and Its Change Under a Mixed-Mode Exercise Intervention in Progressively Dysglycemic Subjects
Authors: Szczerbinski Lukasz , Golonko Aleksandra , Taylor Mark , Puchta Urszula , Konopka Paulina , Paszko Adam , Citko Anna , Szczerbinski Karol , Gorska Maria , Zabielski Piotr , Błachnio-Zabielska Agnieszka , Larsen Steen , Kretowski Adam
Published: December 2021

Skeletal muscles play an essential role in whole-body glucose homeostasis. They are a key organ system engaged in the development of insulin resistance, and also a crucial tissue mediating the beneficial metabolic effects of physical activity. However, molecular mechanisms underlying both these processes in skeletal muscle remain unclear. The aim of our study was to compare metabolomic profiles in skeletal muscle of patients at different stages of dysglycemia, from normoglycemia through prediabetes to T2D, and its changes under a mixed-mode (strength and endurance) exercise intervention. We performed targeted metabolomics comprising several major metabolite classes, including amino acids, biogenic amines and lipid subgroups in skeletal muscles of male patients. Dysglycemic groups differed significantly at baseline in lysophosphatidylcholines, phosphatidylcholines, sphingomyelins, glutamine, ornithine, and carnosine. Following the exercise intervention, we detected significant changes in lipids and metabolites related to lipid metabolism, including in ceramides and acylcarnitines. With their larger and more significant change over the intervention and among dysglycemic groups, these findings suggest that lipid species may play a predominant role in both the pathogenesis of type 2 diabetes and its protection by exercise. Simultaneously, we demonstrated that amino acid metabolism, especially glutamate dysregulation, is correlated to the development of insulin resistance and parallels disturbances in lipid metabolites.
Use of Thyroid Hormones in Hypothyroid and Euthyroid Patients: A 2020 THESIS Questionnaire Survey of Members of the Swedish Endocrine Society
Authors: Planck Tereza , Lantz Mikael , Perros Petros , Papini Enrico , Attanasio Roberto , Nagy Endre V. , Hegedüs Laszlo
Published: December 2021

Background

The standard treatment of hypothyroidism is levothyroxine (LT-4). However, there are several controversies regarding treatment of hypothyroid patients.

Aim

To investigate the Swedish endocrinologists’ use of thyroid hormones in hypothyroid and euthyroid individuals.

Methods

Physician members of the Swedish Endocrine Society (SEF) were invited by e-mail to participate in an online survey investigating this topic.

Results

Out of the eligible 411 members, 116 (28.2%) responded. The majority (98.9%) stated that L-T4 is the treatment of choice. However, around 50% also prescribed liothyronine (L-T3) or a combination of L-T4+L-T3 in their practice. Combination therapy was mostly (78.5%) used in patients with persistent hypothyroid symptoms despite biochemical euthyroidism on L-T4 treatment. Most respondents prescribed L-T4 tablets and did not expect any major changes with alternative formulations such as soft-gel capsules or liquid formulations in situations influencing the bioavailability of L-T4. In euthyroid patients, 49.5% replied that treatment with thyroid hormones was never indicated, while 47.3% would consider L-T4 for euthyroid infertile women with high thyroid peroxidase (TPO) antibody levels.

Conclusion

The treatment of choice for hypothyroidism in Sweden is L-T4 tablets. Combination therapy with L-T4+L-T3 tablets was considered for patients with persistent symptoms despite biochemical euthyroidism. Soft-gel capsules and liquid solutions of L-T4 were infrequently prescribed. Swedish endocrinologists’ deviation from endocrine society guidelines merits further study.
Dynamic Reliability Evaluation of Diesel Generator System of One Chinese 1000MWe NPP Considering Temporal Failure Effects
Authors: Guo Dingqing , Yang Manjiang , Wu Hongmei , Ge Daochuan , Cao Xuewu
Published: December 2021

Loss of power supply from the diesel generator system (DGS) after loss of offsite power (LOOP) will pose great threat to the safety of GEN-II pressurized water reactors (PWR). Therefore, it is very desirable to evaluate the DGS’s reliability. The traditional analyzing tools are limited to static approaches neglecting the dynamic sequence failure behaviors, such as reliability block diagram (RBD), static fault tree (SFT). Static reliability modeling techniques are not capable of capturing the dynamic sequence-dependent failure behaviors typically existing in NPP safety systems such as DGS, and thus often overestimate the unreliability of systems. In this paper, motivated to study the effects of sequence failure behaviors, dynamic fault tree (DFT) is applied to evaluate the reliability of the DGS of one Chinese 1000MWe Nuclear Power Plant (NPP), and an integrated two-phased Markov Chain model is also developed, which can be considered as a contribution of this article. Comparative study of DGS reliability between DFT and SFT is carried out. The results indicate that compared with the result derived from the DFT model, the unreliability of DGS calculated by SFT is greatly overestimated by about one to two orders of magnitude. Therefore, DFT has a potential to improve the economy of NPP by relaxing the overestimated unreliability of nuclear power systems.
OC-SLAM: Steadily Tracking and Mapping in Dynamic Environments
Authors: Wu Zhenyu , Deng Xiangyu , Li Shengming , Li Yingshun
Published: December 2021

Visual Simultaneous Localization and Mapping (SLAM) system is mainly used in real-time localization and mapping tasks of robots in various complex environments, while traditional monocular vision algorithms are struggling to cope with weak texture and dynamic scenes. To solve these problems, this work presents an object detection and clustering assisted SLAM algorithm (OC-SLAM), which adopts a faster object detection algorithm to add semantic information to the image and conducts geometrical constraint on the dynamic keypoints in the prediction box to optimize the camera pose. It also uses RGB-D camera to perform dense point cloud reconstruction with the dynamic objects rejected, and facilitates European clustering of dense point clouds to jointly eliminate dynamic features combining with object detection algorithm. Experiments in the TUM dataset indicate that OC-SLAM enhances the localization accuracy of the SLAM system in the dynamic environments compared with original algorithm and it has shown impressive performance in the localizition and can build a more precise dense point cloud map in dynamic scenes.
Robust Climate Change Adaptation for Environmental Flows in the Goulburn River, Australia
Authors: John Andrew , Horne Avril , Nathan Rory , Fowler Keirnan , Webb J. Angus , Stewardson Michael
Published: December 2021

Climate change presents severe risks for the implementation and success of environmental flows worldwide. Current environmental flow assessments tend to assume climate stationarity, so there is an urgent need for robust environmental flow programs that allow adaptation to changing flow regimes due to climate change. Designing and implementing robust environmental flow programs means ensuring environmental objectives are achieved under a range of uncertain, but plausible climate futures. We apply stress testing concepts previously adopted in water supply management to environmental flows at a catchment scale. We do this by exploring vulnerabilities in different river management metrics for current environmental flow arrangements in the Goulburn River, Australia, under non-stationary climatic conditions. Given the limitations of current environmental flows in supporting ecological outcomes under climate change, we tested three different adaptation options individually and in combination. Stress testing adaptation results showed that increasing environmental entitlements yielded the largest benefits in drier climate futures, whereas relaxing river capacity constraints (allowing more targeted delivery of environmental water) offered more benefits for current and wetter climates. Combining both these options led to greater than additive improvements in allocation reliability and reductions in environmental water shortfalls, and these improvements were achieved across a wider range of climatic conditions than possible with either of the individual options. However, adaptation may present additional risks to some ecological outcomes for wetter climates. Ultimately, there was a degree of plausible climate change beyond which none of the adaptation options considered were effective at improving ecological outcomes. This study demonstrates an important step for environmental flow assessments: evaluating the feasibility of environmental outcomes under climate change, and the intervention options that prove most robust under an uncertain future.
United States Forest Service Use of Forest Inventory Data: Examples and Needs for Small Area Estimation
Authors: Wiener Sarah S. , Bush Renate , Nathanson Amy , Pelz Kristen , Palmer Marin , Alexander Mara L. , Anderson David , Treasure Emrys , Baggs Joanne , Sheffield Ray
Published: December 2021

Forest Inventory and Analysis (FIA) data provides robust information for the United States Forest Service’s (USFS) mid-to-broad-scale planning and assessments, but ecological challenges (i.e., climate change, wildfire) necessitate increasingly strategic information without significantly increasing field sampling. Small area estimation (SAE) techniques could provide more precision supported by a rapidly growing suite of landscape-scale datasets. We present three Regional case studies demonstrating current FIA uses, how SAE techniques could enhance existing uses, and steps FIA could take to enable SAE applications that are user-friendly, comprehensive, and statistically appropriate. The Northern Region uses FIA data for planning and assessments, but SAE techniques could provide more specificity to guide vegetation management activities. State and transition simulation models (STSM) are run with FIA data in the Southwestern Region to predict effects of treatments and disturbances, but SAE could support model validation and more precision to identify treatable areas. The Southern Region used FIA to identify existing longleaf pine stands and evaluate condition, but SAE techniques within FIA tools would streamline analyses. Each case study demonstrates a desire to have FIA data on non-forested conditions and non-tree variables. Additional tools to measure statistical confidence would help maximize utility. FIA’s SAE techniques could add value to a widely used data set, if FIA can support key supplements to basic data and functionality.
Findings from the Hispanic Community Health Study/Study of Latinos on the Importance of Sociocultural Environmental Interactors: Polygenic Risk Score-by-Immigration and Dietary Interactions
Authors: McArdle Cristin E. , Bokhari Hassan , Rodell Clinton C. , Buchanan Victoria , Preudhomme Liana K. , Isasi Carmen R. , Graff Mariaelisa , North Kari , Gallo Linda C. , Pirzada Amber , Daviglus Martha L. , Wojcik Genevieve , Cai Jianwen , Perreira Krista , Fernandez-Rhodes Lindsay
Published: December 2021

Introduction: Hispanic/Latinos experience a disproportionate burden of obesity. Acculturation to US obesogenic diet and practices may lead to an exacerbation of innate genetic susceptibility. We examined the role of gene–environment interactions to better characterize the sociocultural environmental determinants and their genome-scale interactions, which may contribute to missing heritability of obesity. We utilized polygenic risk scores (PRSs) for body mass index (BMI) to perform analyses of PRS-by-acculturation and other environmental interactors among self-identified Hispanic/Latino adults from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

Methods: PRSs were derived using genome-wide association study (GWAS) weights from a publicly available, large meta-analysis of European ancestry samples. Generalized linear models were run using a set of a priori acculturation-related and environmental factors measured at visit 1 (2008–2011) and visit 2 (2014–2016) in an analytic subsample of 8,109 unrelated individuals with genotypic, phenotypic, and complete case data at both visits. We evaluated continuous measures of BMI and waist-to-hip ratio. All models were weighted for complex sampling design, combined, and sex-stratified.

Results: Overall, we observed a consistent increase of BMI with greater PRS across both visits. We found the best-fitting model adjusted for top five principal components of ancestry, sex, age, study site, Hispanic/Latino background genetic ancestry group, sociocultural factors and PRS interactions with age at immigration, years since first arrival to the United States (p < 0.0104), and healthy diet (p < 0.0036) and explained 16% of the variation in BMI. For every 1-SD increase in PRS, there was a corresponding 1.10 kg/m2 increase in BMI (p < 0.001). When these results were stratified by sex, we observed that this 1-SD effect of PRS on BMI was greater for women than men (1.45 vs. 0.79 kg/m2, p < 0.001).

Discussion: We observe that age at immigration and the adoption of certain dietary patterns may play a significant role in modifying the effect of genetic risk on obesity. Careful consideration of sociocultural and immigration-related factors should be evaluated. The role of nongenetic factors, including the social environment, should not be overlooked when describing the performance of PRS or for promoting population health in understudied populations in genomics.
AKR1A1 Variant Associated With Schizophrenia Causes Exon Skipping, Leading to Loss of Enzymatic Activity
Authors: Iino Kyoka , Toriumi Kazuya , Agarie Riko , Miyashita Mitsuhiro , Suzuki Kazuhiro , Horiuchi Yasue , Niizato Kazuhiro , Oshima Kenichi , Imai Atsushi , Nagase Yukihiro , Kushima Itaru , Koike Shinsuke , Ikegame Tempei , Jinde Seiichiro , Nagata Eiichiro , Washizuka Shinsuke , Miyata Toshio , Takizawa Shunya , Hashimoto Ryota , Kasai Kiyoto , Ozaki Norio , Itokawa Masanari , Arai Makoto
Published: December 2021

Schizophrenia is a heterogeneous psychiatric disorder characterized by positive symptoms such as hallucinations and delusions, negative symptoms such as anhedonia and flat affect, and cognitive impairment. Recently, glucuronate (GlucA) levels were reported to be significantly higher in serum of patients with schizophrenia than those in healthy controls. The accumulation of GlucA is known to be related to treatment-resistant schizophrenia, since GlucA is known to promote drug excretion by forming conjugates with drugs. However, the cause of GlucA accumulation remains unclear. Aldo-keto reductase family one member A1 (AKR1A1) is an oxidoreductase that catalyzes the reduction of GlucA. Genetic loss of AKR1A1 function is known to result in the accumulation of GlucA in rodents. Here, we aimed to explore genetic defects in AKR1A1 in patients with schizophrenia, which may result in the accumulation of GlucA. We identified 28 variants of AKR1A1 in patients with schizophrenia and control subjects. In particular, we identified a silent c.753G > A (rs745484618, p. Arg251Arg) variant located at the first position of exon 8 to be associated with schizophrenia. Using a minigene assay, we found that the c.753G > A variant induced exon 8 skipping in AKR1A1, resulting in a frameshift mutation, which in turn led to truncation of the AKR1A1 protein. Using the recombinant protein, we demonstrated that the truncated AKR1A1 completely lost its activity. Furthermore, we showed that AKR1A1 mRNA expression in the whole blood cells of individuals with the c.753G > A variant tended to be lower than that in those without the variants, leading to lower AKR activity. Our findings suggest that AKR1A1 carrying the c.753G > A variant induces exon skipping, leading to a loss of gene expression and enzymatic activity. Thus, GlucA patients with schizophrenia with the c.753G > A variant may show higher GlucA levels, leading to drug-resistant schizophrenia, since drug excretion by GlucA is enhanced.
Longitudinal Cytokine Profile in Patients With Mild to Critical COVID-19
Authors: Ling Lowell , Chen Zigui , Lui Grace , Wong Chun Kwok , Wong Wai Tat , Ng Rita W. Y. , Tso Eugene Y. K. , Fung Kitty S. C. , Chan Veronica , Yeung Apple C. M. , Hui David S. C. , Chan Paul K. S.
Published: December 2021

The cytokine release syndrome has been proposed as the driver of inflammation in coronavirus disease 2019 (COVID-19). However, studies on longitudinal cytokine profiles in patients across the whole severity spectrum of COVID-19 are lacking. In this prospective observational study on adult COVID-19 patients admitted to two Hong Kong public hospitals, cytokine profiling was performed on blood samples taken during early phase (within 7 days of symptom onset) and late phase (8 to 12 days of symptom onset). The primary objective was to evaluate the difference in early and late cytokine profiles among patient groups with different disease severity. The secondary objective was to assess the associations between cytokines and clinical endpoints in critically ill patients. A total of 40 adult patients (mild = 8, moderate = 15, severe/critical = 17) hospitalized with COVID-19 were included in this study. We found 22 cytokines which were correlated with disease severity, as proinflammatory Th1-related cytokines (interleukin (IL)-18, interferon-induced protein-10 (IP-10), monokine-induced by gamma interferon (MIG), and IL-10) and ARDS-associated cytokines (IL-6, monocyte chemoattractant protein-1 (MCP-1), interleukin-1 receptor antagonist (IL-1RA), and IL-8) were progressively elevated with increasing disease severity. Furthermore, 11 cytokines were consistently different in both early and late phases, including seven (growth-regulated oncogene-alpha (GRO-α), IL-1RA, IL-6, IL-8, IL-10, IP-10, and MIG) that increased and four (FGF-2, IL-5, macrophage-derived chemokine (MDC), and MIP-1α) that decreased from mild to severe/critical patients. IL-8, followed by IP-10 and MDC were the best performing early biomarkers to predict disease severity. Among critically ill patients, MCP-1 predicted the duration of mechanical ventilation, highest norepinephrine dose administered, and length of intensive care stay.
Regulation of Plant Immunity by Nuclear Membrane-Associated Mechanisms
Authors: Fang Yiling , Gu Yangnan
Published: December 2021

Unlike animals, plants do not have specialized immune cells and lack an adaptive immune system. Instead, plant cells rely on their unique innate immune system to defend against pathogens and coordinate beneficial interactions with commensal and symbiotic microbes. One of the major convergent points for plant immune signaling is the nucleus, where transcriptome reprogramming is initiated to orchestrate defense responses. Mechanisms that regulate selective transport of nuclear signaling cargo and chromatin activity at the nuclear boundary play a pivotal role in immune activation. This review summarizes the current knowledge of how nuclear membrane-associated core protein and protein complexes, including the nuclear pore complex, nuclear transport receptors, and the nucleoskeleton participate in plant innate immune activation and pathogen resistance. We also discuss the role of their functional counterparts in regulating innate immunity in animals and highlight potential common mechanisms that contribute to nuclear membrane-centered immune regulation in higher eukaryotes.
B Cell Intrinsic STING Signaling Is Not Required for Autoreactive Germinal Center Participation
Authors: Green Kenneth , Wittenborn Thomas R. , Fahlquist-Hagert Cecilia , Terczynska-Dyla Ewa , van Campen Nina , Jensen Lisbeth , Reinert Line , Hartmann Rune , Paludan Søren R. , Degn Søren E.
Published: December 2021

Germinal centers (GCs) are induced microanatomical structures wherein B cells undergo affinity maturation to improve the quality of the antibody response. Although GCs are crucial to appropriate humoral responses to infectious challenges and vaccines, many questions remain about the molecular signals driving B cell participation in GC responses. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is an important mediator of type I interferon and proinflammatory cytokine responses during infection and cellular stress. Recent studies have reported important roles for STING in B cell responses, including an impact on GC B cells and downstream antibody responses, which could have great consequences for vaccine design and understanding STING-associated interferonopathies. GCs are also involved in untoward reactions to autoantigens in a plethora of autoimmune disorders, and it is generally thought that these responses coopt the mechanisms used in foreign antigen-directed GCs. Here, we set out to investigate the importance of the cGAS-STING pathway in autoreactive B cell responses. In a direct competition scenario in a murine mixed bone marrow chimera model of autoreactive GCs, we find that B cell intrinsic deficiency of cGAS, STING, or the type I interferon receptor IFNAR, does not impair GC participation, whereas Toll-like receptor (TLR)-7 deficiency mediates a near-complete block. Our findings suggest that physiological B cell responses are strictly sustained by signals linked to BCR-mediated endocytosis. This wiring of B cell signals may enable appropriate antibody responses, while at the same time restricting aberrant antibody responses during infections and in autoimmune or autoinflammatory settings.
Identifying Changes in Peripheral Lymphocyte Subpopulations in Adult Onset Type 1 Diabetes
Authors: Teniente-Serra Aina , Pizarro Eduarda , Quirant-Sánchez Bibiana , Fernández Marco A. , Vives-Pi Marta , Martinez-Caceres Eva M.
Published: December 2021

T- and B-lymphocytes play an important role in the pathogenesis of type 1 diabetes (T1D), a chronic disease caused by the autoimmune destruction of the insulin-producing cells in the pancreatic islets. Flow cytometry allows their characterization in peripheral blood, letting to investigate changes in cellular subpopulations that can provide insights in T1D pathophysiology. With this purpose, CD4+ and CD8+ T cells (including naïve, central memory, effector memory and terminally differentiated effector (TEMRA), Th17 and Tregs) and B cells subsets (naïve, unswitched memory, switched memory and transitional B cells) were analysed in peripheral blood of adult T1D patients at disease onset and after ≥2 years using multiparametric flow cytometry. Here we report changes in the percentage of early and late effector memory CD4+ and CD8+ T cells as well as of naïve subsets, regulatory T cells and transitional B cells in peripheral blood of adult patients at onset of T1D when compared with HD. After 2 years follow-up these changes were maintained. Also, we found a decrease in percentage of Th17 and numbers of T cells with baseline. In order to identify potential biomarkers of disease, ROC curves were performed being late EM CD4 T cell subset the most promising candidate. In conclusion, the observed changes in the percentage and/or absolute number of lymphocyte subpopulations of adult T1D patients support the hypothesis that effector cells migrate to the pancreas and this autoimmune process perseveres along the disease. Moreover, multiparametric flow allows to identify those subsets with potential to be considered biomarkers of disease.
Intestinal Stem Cell-on-Chip to Study Human Host-Microbiota Interaction
Authors: Siwczak Fatina , Loffet Elise , Kaminska Mathilda , Koceva Hristina , Mahe Maxime M. , Mosig Alexander S.
Published: December 2021

The gut is a tubular organ responsible for nutrient absorption and harbors our intestinal microbiome. This organ is composed of a multitude of specialized cell types arranged in complex barrier-forming crypts and villi covered by a mucosal layer controlling nutrient passage and protecting from invading pathogens. The development and self-renewal of the intestinal epithelium are guided by niche signals controlling the differentiation of specific cell types along the crypt-villus axis in the epithelium. The emergence of microphysiological systems, or organ-on-chips, has paved the way to study the intestinal epithelium within a dynamic and controlled environment. In this review, we describe the use of organ-on-chip technology to control and guide these differentiation processes in vitro. We further discuss current applications and forthcoming strategies to investigate the mechanical processes of intestinal stem cell differentiation, tissue formation, and the interaction of the intestine with the microbiota in the context of gastrointestinal diseases.
Biologics for Psoriasis During the COVID-19 Pandemic
Authors: Zeng Huanhuan , Wang Siyu , Chen Ling , Shen Zhu
Published: December 2021

Coronavirus disease 2019 (COVID-19), a new form of acute infectious respiratory syndrome first reported in 2019, has rapidly spread worldwide and has been recognized as a pandemic by the WHO. It raised widespread concern about the treatment of psoriasis in this COVID-19 pandemic era, especially on the biologics use for patients with psoriasis. This review will summarize key information that is currently known about the relationship between psoriasis, biological treatments, and COVID-19, and vaccination-related issues. We also provide references for dermatologists and patients when they need to make clinical decisions. Currently, there is no consensus on whether biological agents increase the risk of coronavirus infection; however, current research shows that biological agents have no adverse effects on the prognosis of patients with COVID-19 with psoriasis. In short, it is not recommended to stop biological treatment in patients with psoriasis to prevent the infection risk, and for those patients who tested positive for SARS-CoV-2, the decision to pause biologic therapy should be considered on a case-by-case basis, and individual risk and benefit should be taken into account. Vaccine immunization against SARS-CoV-2 is strictly recommendable in patients with psoriasis without discontinuation of their biologics but evaluating the risk-benefit ratio of maintaining biologics before vaccination is mandatory at the moment.
Comparative Genomics of Novel Agrobacterium G3 Strains Isolated From the International Space Station and Description of Agrobacterium tomkonis sp. nov.
Authors: Singh Nitin K. , Lavire Céline , Nesme Joseph , Vial Ludovic , Nesme Xavier , Mason Christopher E. , Lassalle Florent , Venkateswaran Kasthuri
Published: December 2021

Strains of Agrobacterium genomospecies 3 (i.e., genomovar G3 of the Agrobacterium tumefaciens species complex) have been previously isolated from diverse environments, including in association with plant roots, with algae, as part of a lignocellulose degrading community, from a hospital environment, as a human opportunistic pathogen, or as reported in this study, from a surface within the International Space Station. Polyphasic taxonomic methods revealed the relationship of Agrobacterium G3 strains to other Agrobacterium spp., which supports the description of a novel species. The G3 strains tested (n = 9) were phenotypically distinguishable among the strains from other genomospecies of the genus Agrobacterium. Phylogenetic analyses of the 16S rRNA gene, gyrB gene, multi-locus sequence analysis, and 1,089-gene core-genome gene concatenate concur that tested G3 strains belong to the Agrobacterium genus and they form a clade distinct from other validly described Agrobacterium species. The distinctiveness of this clade was confirmed by average nucleotide identity (ANI) and in silico digital DNA–DNA hybridization (dDDH) comparisons between the G3 tested strains and all known Agrobacterium species type strains, since obtained values were considerably below the 95% (ANI) and 70% (dDDH) thresholds used for the species delineation. According to the core-genome phylogeny and ANI comparisons, the closest relatives of G3 strains were Agrobacterium sp. strains UGM030330-04 and K599, members of a novel genomospecies we propose to call genomovar G21. Using this polyphasic approach, we characterized the phenotypic and genotypic synapomorphies of Agrobacterium G3, showing it is a bona fide bacterial species, well separated from previously named Agrobacterium species or other recognized genomic species. We thus propose the name Agrobacterium tomkonis for this species previously referred to as Agrobacterium genomospecies 3. The type strain of A. tomkonis is IIF1SW-B1T (= LMG 32164 = NRRL B-65602). Comparative genomic analysis show A. tomkonis strains have species-specific genes associated with secretion of secondary metabolites, including an exopolysaccharide and putative adhesins and resistance to copper. A. tomkonis specific gene functions notably relate to surface adhesion and could be involved to colonize nutrient-poor and harsh habitats. The A. tomkonis strains from the ISS showed presence of a 40-kbp plasmid and several other potential mobile genetic elements detected that could also be part of conjugative elements or integrated prophages.
Sinking Rate and Community Structures of Autumn Phytoplankton Responses to Mesoscale Physical Processes in the Western South China Sea
Authors: Mao Yingjie , Li Xiaoqian , Zhang Guicheng , Liao Yan , Qian Gang , Sun Jun
Published: December 2021

To examine the influence of mesoscale eddy on the natural phytoplankton community and its sinking rate changes, a comprehensive investigation cruise was carried out in the western South China Sea in autumn 2016. A total of 108 phytoplankton species were found, which belong to 54 phytoplankton genera; most of them were dominated by Dinophyta (54 genera), followed by Bacillariophyta (50 genera), Cyanophyta (3 genera), and Chrysophyta (1 genus). Bacillariophyta and Dinophyta were the main phytoplankton communities in the investigated sea area. The sinking rate of phytoplankton ranged from 0.12 to 3.17 m day–1, determined by the SETCOL method. The highest phytoplankton sinking rate was found in the 200-m water layer, followed by the DCM layer. No significant correlation was found between phytoplankton sinking rates and most of the environmental parameters during this cruise. At a similar time, we have carried out the estimation of carbon flux in the investigated sea area by using the sinking rate of phytoplankton, which showed that the carbon flux ranged from 2.41 × 10–6 to 0.006 mg C m–2 day–1; in addition, the maximum was at the 200-m layer. Phytoplankton community and sinking rate were significantly affected by the mesoscale eddy processes. The cold eddy could affect the community distribution of diatom and dinoflagellate, and the upwelling mainly affects the community of dinoflagellate. Both of them could contribute to a higher sedimentation rate of phytoplankton in the surface and DCM layers. Warm eddy could reduce the abundance of phytoplankton in the surface layer; simultaneously, the sinking rate of phytoplankton in the shallow water layer above 100 m is also reduced. These results can fill in the knowledge gap of mesoscale eddy processes in the study of phytoplankton community change and sinking rate; furthermore, it can provide insights into phytoplankton carbon and its implementation in further carbon sink.
SEMA6B Overexpression Predicts Poor Prognosis and Correlates With the Tumor Immunosuppressive Microenvironment in Colorectal Cancer
Authors: Li Tiegang , Yan Zheng , Wang Weiqi , Zhang Rixin , Gan Wenqiang , Lv Silin , Zeng Zifan , Hou Yufang , Yang Min
Published: December 2021

Background: Semaphorin 6b (SEMA6B) is a member of the semaphorin axon-guidance family and has been demonstrated to both induce and inhibit tumor progression. However, the role of SEMA6B in colorectal cancer (CRC) has remained unclear. This study sought to explore the promising prognostic biomarker for CRC and to understand the expression pattern, clinical significance, immune effects, and biological functions of SEMA6B.

Methods: SEMA6B expression in CRC was evaluated via multiple gene and protein expression databases and we identified its prognostic value through The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Correlations between SEMA6B expression and components of the tumor immune microenvironment were analyzed by packages implemented in R, Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), and Tumor-Immune System Interactions database (TISIDB). RNA interference was performed to silence the expression of SEMA6B to explore its biological roles in the colon cancer cell lines HCT116 and LoVo.

Results: The messenger RNA (mRNA) level of SEMA6B and the protein expression were higher in CRC tissues than adjacent normal tissues from multiple CRC datasets. High SEMA6B expression was significantly associated with dismal survival. Multivariate Cox regression analysis demonstrated that SEMA6B was an independent prognostic factor for progression-free survival (PFS). The nomogram showed a favorable predictive ability in PFS. Functional enrichment analysis and the Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm revealed that the gene cluster associated with the high SEMA6B group were prominently involved in immune responses and inflammatory activities. Notably, SEMA6B expression was positively correlated with infiltrating levels of CD4+ T cells, macrophages, myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), neutrophils, and dendritic cells. Moreover, SEMA6B expression displayed strong correlations with diverse marker sets of immunosuppressive cells in CRC. Integrative analysis revealed that immunosuppressive molecules and immune checkpoints were markedly upregulated in CRC samples with high SEMA6B expression. Furthermore, knockdown of SMEA6B in colon cancer cells significantly inhibited cell proliferation, migration, invasion and reduced the mRNA levels of immunosuppressive molecules.

Conclusion: Our findings provide evidence that high SEMA6B expression correlated with adverse prognosis and the tumor immunosuppressive microenvironment in CRC patients. Therefore, SEMA6B may serve as a novel prognostic biomarker for CRC, which offers further insights into developing CRC-targeted immunotherapies.
Prognostic Value of mRNAsi/Corrected mRNAsi Calculated by the One-Class Logistic Regression Machine-Learning Algorithm in Glioblastoma Within Multiple Datasets
Authors: Zhang Mingwei , Chen Hong , Liang Bo , Wang Xuezhen , Gu Ning , Xue Fangqin , Yue Qiuyuan , Zhang Qiuyu , Hong Jinsheng
Published: December 2021

Glioblastoma (GBM) is the most common glial tumour and has extremely poor prognosis. GBM stem-like cells drive tumorigenesis and progression. However, a systematic assessment of stemness indices and their association with immunological properties in GBM is lacking. We collected 874 GBM samples from four GBM cohorts (TCGA, CGGA, GSE4412, and GSE13041) and calculated the mRNA expression-based stemness indices (mRNAsi) and corrected mRNAsi (c_mRNAsi, mRNAsi/tumour purity) with OCLR algorithm. Then, mRNAsi/c_mRNAsi were used to quantify the stemness traits that correlated significantly with prognosis. Additionally, confounding variables were identified. We used discrimination, calibration, and model improvement capability to evaluate the established models. Finally, theCIBERSORTxalgorithm and ssGSEA were implemented for functional analysis. Patients with high mRNAsi/c_mRNAsi GBM showed better prognosis among the four GBM cohorts. After identifying the confounding variables, c_mRNAsi still maintained its prognostic value. Model evaluation showed that the c_mRNAsi-based model performed well. Patients with high c_mRNAsi exhibited significant immune suppression. Moreover, c_mRNAsi correlated negatively with infiltrating levels of immune-related cells. In addition, ssGSEA revealed that immune-related pathways were generally activated in patients with high c_mRNAsi. We comprehensively evaluated GBM stemness indices based on large cohorts and established a c_mRNAsi-based classifier for prognosis prediction.
The Variants at APOA1 and APOA4 Contribute to the Susceptibility of Schizophrenia With Inhibiting mRNA Expression in Peripheral Blood Leukocytes
Authors: Fan Yao , Gao Jun , Li Yinghui , Chen Xuefei , Zhang Ting , You Weiyan , Xue Yong , Shen Chong
Published: December 2021

Objective: Abnormal lipid metabolism has a close link to the pathophysiology of schizophrenia (SZ). This study mainly aimed to evaluate the association of variants at apolipoprotein A1 (APOA1) and APOA4 with SZ in a Chinese Han population.

Methods: The rs5072 of APOA1 and rs1268354 of APOA4 were examined in a case–control study involving 2,680 patients with SZ from the hospital and 2,223 healthy controls screened by physical examination from the community population. The association was estimated with the odds ratio (OR) and 95% confidence intervals (95% CIs) by logistic regression. The APOA1 and APOA4 messenger RNA (mRNA) in peripheral blood leukocytes were measured by real-time PCR and compared between SZ cases and controls. Serum apoA1 levels were detected by turbidimetric inhibition immunoassay and high-density lipoprotein cholesterol (HDL-C) levels were detected by the homogeneous method.

Results: Both of the rs5072 of APOA1 and rs1268354 of APOA4 had statistically significant associations with SZ. After adjustment for age and sex, ORs (95% CIs) of the additive model of rs5072 and rs1268354 were 0.82 (0.75–0.90) and 1.120 (1.03–1.23), and p-values were 3.22 × 10−5 and 0.011, respectively. The association of rs5072 with SZ still presented statistical significance even after Bonferroni correction (p-value×6). SZ patients during the episode presented lower levels of apoA1, HDL-C, mRNA of APOA1 common variants and transcript variant 4, and APOA4 mRNA than controls (p < 0.01) while SZ patients in remission showed a significantly decreased APOA1 transcript variant 3 expression level and increased APOA4 mRNA expression level (p < 0.01). mRNA expression levels of APOA1 transcript variant 4 significantly increased with the variations of rs5072 in SZ during the episode (ptrend = 0.017). After the SZ patients received an average of 27.50 ± 9.90 days of antipsychotic treatment, the median (interquartile) of serum apoA1 in the SZ episode significantly increased from 1.03 (1.00.1.20) g/L to 1.08 (1.00.1.22) g/L with the p-value of 0.044.

Conclusion: Our findings suggest that the genetic variations of APOA1 rs5072 and APOA4 rs1268354 contribute to the susceptibility of SZ, and the expression levels of APOA1 and APOA4 mRNA of peripheral blood leukocytes decreased in SZ patients during the episode while APOA4 increased after antipsychotic treatment.