bluuebunny/crossref_metadata_2025 huggingface dataset:
On-The-Fly Kinetics of the Hydrogen Abstraction by Hydroperoxyl Radical: An Application of the Reaction Class Transition State Theory
Authors: Baradyn Maciej , Ratkiewicz Artur
Published: January 2022

A Reaction Class Transition State Theory (RC-TST) is applied to calculate thermal rate constants for hydrogen abstraction by OOH radical from alkanes in the temperature range of 300–2500 K. The rate constants for the reference reaction C2H6 + ∙OOH → ∙C2H5 + H2O2, is obtained with the Canonical Variational Transition State Theory (CVT) augmented with the Small Curvature Tunneling (SCT) correction. The necessary parameters were obtained from M06-2X/aug-cc-pVTZ data for a training set of 24 reactions. Depending on the approximation employed, only the reaction energy or no additional parameters are needed to predict the RC-TST rates for other class representatives. Although each of the reactions can in principle be investigated at higher levels of theory, the approach provides a nearly equally reliable rate constant at a fraction of the cost needed for larger and higher level calculations. The systematic error is smaller than 50% in comparison with high level computations. Satisfactory agreement with literature data, augmented by the lack of necessity of tedious and time consuming transition state calculations, facilitated the seamless application of the proposed methodology to the Automated Reaction Mechanism Generators (ARMGs) programs.
Investigating English in Multilingual Contexts Online: Identity Construction in Geotagged Instagram Data
Authors: Mohr Susanne
Published: January 2022

Tourism discourse, referring to communication in tourism as global industry, contributes to the creation of tourist spaces, where space is a social and affective construct as opposed to place as a geographical one. Tourists and hosts are part of these spaces and form them with their language practices, both offline and online. This article presents a case study of tourism discourse related to Zanzibar on Instagram, focusing particularly on linguistic repertoires, the role of English in them and language choices as well as their implications for identity construction. A central issue, in line with discourse-centred online ethnography, is the comparison of the digital data with previously collected data from the physical tourist space. Theoretically and methodologically, the concept of (linguistic) transnationalism is central for the study, which uses geotags and hashtags as means of data retrieval and framework of analysis to further this concept.
Prognostic Value of Coronary CT Angiography-Derived Fractional Flow Reserve in Non-obstructive Coronary Artery Disease: A Prospective Multicenter Observational Study
Authors: Zhou Fan , Chen Qian , Luo Xiao , Cao Wei , Li Ziwen , Zhang Bo , Schoepf U. Joseph , Gill Callum E. , Guo Lili , Gao Hong , Li Qingyao , Shi Yibing , Tang Tingting , Liu Xiaochen , Wu Honglin , Wang Dongqing , Xu Feng , Jin Dongsheng , Huang Sheng , Li Haige , Pan Changjie , Gu Hongmei , Xie Lixiang , Wang Ximing , Ye Jing , Jiang Jianwei , Zhao Hanqing , Fang Xiangming , Xu Yi , Xing Wei , Li Xiaohu , Yin Xindao , Lu Guang Ming , Zhang Long Jiang
Published: January 2022

Coronary artery disease (CAD) is a major contributor to morbidity and mortality worldwide. Myocardial ischemia may occur in patients with normal or non-obstructive CAD on invasive coronary angiography (ICA). The comprehensive evaluation of coronary CT angiography (CCTA) integrated with fractional flow reserve derived from CCTA (CT-FFR) to CAD may be essential to improve the outcomes of patients with non-obstructive CAD. China CT-FFR Study-2 (ChiCTR2000031410) is a large-scale prospective, observational study in 29 medical centers in China. The primary purpose is to uncover the relationship between the CCTA findings (including CT-FFR) and the outcome of patients with non-obstructive CAD. At least 10,000 patients with non-obstructive CAD but without previous revascularization will be enrolled. A 5-year follow-up will be performed. The primary endpoint is the occurrence of major adverse cardiovascular events (MACE), including all-cause mortality, non-fatal myocardial infarct, unplanned revascularization, and hospitalization for unstable angina. Clinical characteristics, laboratory and imaging examination results will be collected to analyze their prognostic value.
Case Report: Three-Dimensional Printing–Assisted Surgical Treatment of Complex Body Vein Ectopic Drainage
Authors: Wei Luyao , Sun Guowen , Wu Qin , Zhang Weizhi , Tang Mi , Zhao Tianli , Hu Shijun
Published: January 2022

Introduction

Complex ectopic drainage of body veins is a rare congenital disease. Its preoperative diagnosis and surgical choice can be considerable challenges.

Case Summary

A 5-year-old patient was diagnosed precisely by preoperative transthoracic echocardiography, computed tomography (CT), three-dimensional (3D) reconstruction, and three-dimensional (3D) printing of the heart and great blood vessels. The operation was performed successfully using flexible intraoperative intubation strategies.

Conclusion

3D printing technology can assist in the formulation of surgical protocols for complex body vein ectopic drainage. Flexible intubation strategies can increase the success of the operation.
Assessment of the Impact of Higher Temperatures Due to Climate Change on the Mortality Risk Indexes in Ecuador Until 2070
Authors: Montenegro M. , Campozano L. , Urdiales-Flores D. , Maisincho L. , Serrano-Vincenti S. , Borbor-Cordova M. J.
Published: January 2022

Extreme weather conditions, including intense heat stress due to higher temperatures, could trigger an increase in mortality risk. One way to evaluate the increase in mortality risk due to higher temperatures is the high risk warming (HRW) index, which evaluates the difference between the future and base period of a given percentile of daily maximum temperature (Tmax). Another is to calculate the future increase in the number of days over the temperature of such percentile, named high risk days (HRD) index. Previous studies point to the 84th percentile as the optimum temperature. Thus, this study aims to evaluate HRW and HRD indexes in Ecuador from 2011 to 2070 over the three natural climate zones, e.g., Coast, Andes, and Amazon. This climate analysis is based on historical data from meteorological stations and projections from CSIRO-MK36, GISS-E2, and IPSL-CM5A-MR, CMIP5 global climate models with dynamical scale reduction through weather research forecasting (WRF). The representative concentration pathways (RCPs), 8.5, were considered, which are related to the highest increases in future temperature. The results indicate that HRW and HRD will experience a larger increase in the period 2041–2070 compared with the period 1980–2005; in particular, these two indices will have a progressively increasing trend from 2011 onward. Specifically, the HRW calculated from the CMIP5 models for all stations is expected to grow from 0.6°C to 1.4°C and 1.8°C to 4.6°C for 2010–2040 and 2041–2070, respectively. Also, it is expected that the HRD for all stations will increase from 42 to 74 and 120 to 227 warming days for 2011–2040 and 2041–2070, respectively. The trends derived using Sen’s slope test show an increase in the HRW between 0.5°C and 0.9°C/decade and of the HRD between 2.88 and 4.9 days/decade since 1985. These results imply a high increase in heat-related mortality risks related to climate change in Ecuador. In terms of spatial distribution, three Ecuadorian regions experienced more critical temperature conditions with higher values of HRW and HRD for 2070. As a response to the increased frequency trends of warming periods in tropical areas, urgent measures should be taken to review public policies and legislation to mitigate the impacts of heat as a risk for human health in Ecuador.
Integrated Geophysical Study of the Collision Between the North China Craton and the Yangtze Craton and Its Links With Craton Lithospheric Thinning
Authors: Liu Lihua , Hao Tianyao , Lü Chuanchuan , Wu Zhiqiang , Kim Kwanghee , Kim Hanjoon , Xu Ya
Published: January 2022

Unlike stable cratons elsewhere in the world, the lithosphere is strongly thinned in the east of both the North China Craton (NCC) and the Yangtze Craton (YZC) compared with the west. We deployed four active-source onshore-offshore wide-angle seismic survey lines in the eastern NCC and YZC from 2010 to 2016 with the aim of revealing the mechanism of lithospheric thinning and the process of the collision between the NCC and YZC. We obtained high-resolution crustal P-wave velocity models for the eastern NCC and YZC based on seismic forward modeling, travel-time tomography, and finite-difference wave-field modeling. Based on our integrated geophysical study and previous work, we propose a five-stage model for the collision between the YZC and NCC, with different dominant geodynamic mechanisms in each stage. Our collision model shows that lithospheric thinning in the eastern NCC and YZC is a consequence of the NCC-YZC collision and subduction of the Pacific plate.
Spermine Regulates Immune and Signal Transduction Dysfunction in Diabetic Cardiomyopathy
Authors: Wei Can , Sun Mengting , Liang Xiao , Che Bingbing , Wang Ningning , Shi Lili , Fan Ying
Published: January 2022

Background

Diabetic cardiomyopathy (DCM) is a specific form of cardiomyopathy that is independent of coronary artery disease and hypertension. Exploring the transcriptomics of DCM is of great significance for understanding the biology of the disease and for guiding new therapeutic targets for the potential therapeutic effect of spermine (SPM).

Methods and Results

By using a mouse DCM model, we analyzed the transcriptome of the myocardium, before/after treatment with SPM. Using RNA sequencing (RNA-seq), we identified 1,318 differentially expressed genes (DEGs), with 636 being upregulated and 682 being downregulated in DCM compared to control check (CK). We then identified 1,393 DEGs, with 887 being upregulated and 506 being downregulated in SPM compared to DCM. Kyoto Encyclopedia of Genes And Genomes (KEGG) analysis demonstrated that the DEGs were significantly enriched in the immune system and signal transduction-related pathways. UpSet Venn analysis showed that 174 DEGs in DCM could be reversed by SPM, with 45 candidates related to immune system and related signal transduction pathways. Trend analysis demonstrated the dynamic changes in gene levels in DCM and SPM treatment, shown as 49 immune and signal transduction-related candidates were significantly enriched in some classical pathways, such as complement and coagulation cascades and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway. To further reveal the protective mechanism of SPM to DCM, we predicted 14 overlapped transcription factors (TFs) and their co-factors involved in gene transcription regulation and showed gene interaction with Cytoscape.

Conclusion

The biomarkers and canonical pathways identified in this study may hold the key to understanding the mechanisms of DCM pathobiology and providing new targets for the therapeutic effect of SPM against DCM by targeting abnormal immune response and signal transduction.
NAD+-Increasing Strategies to Improve Cardiometabolic Health?
Authors: Blanco-Vaca Francisco , Rotllan Noemi , Canyelles Marina , Mauricio Didac , Escolà-Gil Joan Carles , Julve Josep
Published: January 2022

Depleted nicotinamide adenine dinucleotide (NAD+) is a common hallmark of metabolic disorders. Therefore, NAD+-increasing strategies have evolved as a potential therapeutic venue to combat cardiometabolic diseases. Several forms of vitamin B3, i.e., nicotinamide and nicotinamide mononucleotide, and especially nicotinamide riboside, have attracted most interest as potentially safe and efficacious candidates for NAD+ restoration. Herein, we dissected the characteristics of the latest clinical trials testing the therapeutic potential of different vitamin B3 molecules to improve cardiometabolic health, with a special focus on randomized, placebo-controlled clinical trials performed in the context of obesity or other pathologies, mainly linked to cardiovascular system and skeletal muscle functionality. The favorable outcomes via NAD+-increasing strategies found in the different studies were quite heterogeneous. NAD+-increasing interventions improved capacity to exercise, decreased blood pressure, increased the anti-inflammatory profile and insulin-stimulated glucose disposal, and reduced the fat-free mass. Except for the decreased blood pressure, the significant results did not include many hard clinical end points, such as decreases in weight, BMI, fasting glucose, or HbA1c percentage. However, the analyzed trials were short-term interventions. Overall, the accumulated clinical data can be interpreted as moderately promising. Additional and long-term studies will be needed to directly compare the doses and duration of treatments among different vitamin B3 regimes, as well as to define the type of patients, if any, that could benefit from these treatments. In this context, a major point of advancement in delineating future clinical trials would be to identify subjects with a recognized NAD+ deficiency using novel, appropriate biomarkers. Also, confirmation of gender-specific effect of NAD+-increasing treatments would be needed.
Aldose Reductase B1 in Pig Sperm Is Related to Their Function and Fertilizing Ability
Authors: Mateo-Otero Yentel , Ribas-Maynou Jordi , Delgado-Bermúdez Ariadna , Llavanera Marc , Recuero Sandra , Barranco Isabel , Yeste Marc
Published: January 2022

Aldose reductase B1 (AKR1B1) has been reported to participate in the modulation of male and female reproductive physiology in several mammalian species. In spite of this, whether or not AKR1B1 could be related to sperm quality, functionality and fertilizing ability is yet to be elucidated. The present study, therefore, aimed to investigate: i) the presence of AKR1B1 in epididymal and ejaculated sperm; ii) the relationship between the AKR1B1 present in sperm and the physiology of the male gamete; iii) the liaison between the relative content of AKR1B1 in sperm and their ability to withstand preservation for 72 h; and iv) the potential link between sperm AKR1B1 and in vitro fertility outcomes. Immunoblotting revealed that AKR1B1 is present in both epididymal and ejaculated sperm with a similar relative content. Moreover, the relative levels of AKR1B1 in sperm (36 kDa band) were found to be negatively related to several kinematic parameters and intracellular calcium levels, and positively to the percentage of sperm with distal cytoplasmic droplets after storage. Finally, AKR1B1 amounts in sperm (36 kDa band) were negatively associated to fertilization rate at two days post-fertilization and embryo development at six days post-fertilization. The results of the present work suggest that AKR1B1 in sperm is probably acquired during maturation rather than at ejaculation and could play a role in that process. Moreover, AKR1B1 seems to be related to the sperm resilience to preservation and to their fertilizing capacity, as lower levels of the 36 kDa band (putative inactive form of this protein) result in better reproductive outcomes.
Increased Expression of YAP Inhibited the Autophagy Level by Upregulating mTOR Signal in the Eutopic ESCs of Endometriosis
Authors: Pei Tianjiao , Luo Bin , Huang Wei , Liu Dong , Li Yujing , Xiao Li , Huang Xin , Ouyang Yunwei , Zhu Huili
Published: January 2022

We first reported that the Hippo-YAP signaling pathway plays a critical role in the pathogenesis of endometriosis (EMS). Autophagy is also related to the invasion ability of endometrial cells and is involved in the pathogenesis of EMS through multi-levels. However, the precise regulatory mechanism of YAP on autophagy in the eutopic endometrial stromal cells (ESCs) is still unclear. Primary eutopic ESCs of EMS patients (n = 12) and control patients without EMS (n = 9) were isolated and cultured to investigate the expressions of YAP and mTOR, the role of YAP in autophagy, and the effect of the YAP-autophagy signal on the decidualization of the eutopic ESCs. Endometriosis-related sequencing data (GSE51981) in the GEO database were used to find the genes significantly correlated with YAP. We found 155 genes with significant differences in the interaction with YAP in EMS from the dataset, and the autophagy pathway was significantly enriched. Following on from our previous studies of YAP knockdown, overexpression of YAP resulted in an increased expression of mTOR and decreased ratio of LC3-II/LC3-I and autophagy markers, in the eutopic ESCs; transmission electron microscope observation also showed fewer autophagosomes compared with the control cells. Furthermore, ESCs of the Rapamycin-treated group showed significant decidual-like changes with significantly increased decidual prolactin level at 72 h after in vitro decidualization. These results demonstrate that the increased YAP inhibited the level of autophagy by upregulating the mTOR signal in the eutopic ESCs of endometriosis. The YAP-autophagy signal plays an important role in the pathogenesis of endometriosis-associated infertility.
Inconsistent Patterns of Soil Fauna Biodiversity and Soil Physicochemical Characteristic Along an Urbanization Gradient
Authors: Yu Shiqin , Wu Zhifeng , Xu Guoliang , Li Cheng , Wu Zhijian , Li Zengguang , Chen Xiaohua , Lin Miaojun , Fang Xueru , Lin Yongquan
Published: January 2022

Urbanization has induced substantial changes in soil physicochemical characteristic, which plays an important role in regulating soil fauna biodiversity in forests and grasslands. However, less is known about the urbanization effect on soil fauna biodiversity and how soil physicochemical changes mediate this effect. Along an urbanization gradient in the city of Guangzhou, we established four sites with different urbanization intensities, including an urban site, two suburban sites, and a rural site, and then studied their soil physicochemical characteristic and soil fauna biodiversity. The soil physicochemical characteristic dramatically changed along the urbanization gradient. In contrast, the soil fauna biodiversity exhibited a very different pattern. Soil fauna abundance was highest in the suburban sites. Moreover, there were significant changes of Pielou’s evenness and community structure in the suburban sites. Soil fauna biodiversity property in the urban site was similar to that in the rural site, except that the rural site was characterized by Enchytraeidae while the urban site was not characterized by any taxa. Our linear and canonical correspondence analysis models suggested that soil physicochemical characteristic only contributed a little to the variance of soil fauna abundance (19%), taxa number (27%), and community structure (12%). In contrast, soil physicochemical characteristic explained about half of the variance in Shannon’s diversity and Pielou’s evenness. However, with urbanization intensity increasing, soil physicochemical changes could both increase and decrease the diversity and evenness. Thus, our results revealed an inconsistent pattern between soil fauna biodiversity and soil physicochemical characteristic along an urbanization gradient. This study suggested that soil physicochemical change was less important as expected in regulating soil fauna biodiversity pattern under an urbanization context. To elucidate the effect of urbanization on soil fauna biodiversity, further studies should take other urbanization agents into account.
Changes in Soil Properties Following the Establishment of Exclosures in Ethiopia: A Meta-Analysis
Authors: Yakob Getahun , Smith Jo U. , Nayak Dali R. , Hallett Paul D. , Phimister Euan , Mekuria Wolde
Published: January 2022

Community-led watershed development activities, including the establishment of exclosures (areas where both livestock and farming activities are excluded) on degraded communal grazing land, have become a common practice in Ethiopia since the 1990s. However, it is not yet fully understood how these exclosures change soil organic carbon and total soil nitrogen in different soil types and under different agroecologies. A meta-analysis using data gathered from the most relevant peer reviewed articles from Ethiopian exclosure systems was conducted to assess the variation in the effects of exclosures on soil carbon and nitrogen and to investigate the factors controlling change. The results demonstrate that after 16 years, exclosures can increase soil organic carbon and total soil nitrogen up to an effect size greater than two. This is moderated by soil type, exclosure age, landscape position and agroecology. More effective restoration of soil carbon was observed in less developed Leptosols and Cambisols than in more developed Luvisols, and in drier than more humid agroecologies. The results suggest that soil type and agroecology should be taken into consideration when planning and implementing exclosures on degraded communal grazing land. The findings of this study provide base line information for the future expansion of exclosures, and guide where to focus implementation. They also provide criteria to be used when planning and establishing exclosures to restore soil carbon and nitrogen. In addition, the results generated through this meta-analysis provide better understanding of the spatial and temporal variation of the effectiveness of exclosures to restore soil carbon and nitrogen.
Crop Quality Improvement Through Genome Editing Strategy
Authors: Yang Yihao , Xu Chenda , Shen Ziyan , Yan Changjie
Published: January 2022

Good quality of crops has always been the most concerning aspect for breeders and consumers. However, crop quality is a complex trait affected by both the genetic systems and environmental factors, thus, it is difficult to improve through traditional breeding strategies. Recently, the CRISPR/Cas9 genome editing system, enabling efficiently targeted modification, has revolutionized the field of quality improvement in most crops. In this review, we briefly review the various genome editing ability of the CRISPR/Cas9 system, such as gene knockout, knock-in or replacement, base editing, prime editing, and gene expression regulation. In addition, we highlight the advances in crop quality improvement applying the CRISPR/Cas9 system in four main aspects: macronutrients, micronutrients, anti-nutritional factors and others. Finally, the potential challenges and future perspectives of genome editing in crop quality improvement is also discussed.
Protocol: A Multiplexed Reporter Assay to Study Effects of Chromatin Context on DNA Double-Strand Break Repair
Authors: Schep Ruben , Leemans Christ , Brinkman Eva K. , van Schaik Tom , van Steensel Bas
Published: January 2022

DNA double-strand breaks (DSBs) can be repaired through various pathways. Understanding how these pathways are regulated is of great interest for cancer research and optimization of gene editing. The local chromatin environment can affect the balance between repair pathways, but this is still poorly understood. Here we provide a detailed protocol for DSB-TRIP, a technique that utilizes the specific DNA scars left by DSB repair pathways to study pathway usage throughout the genome. DSB-TRIP randomly integrates a repair reporter into many genomic locations, followed by the induction of DSBs in the reporter. Multiplexed sequencing of the resulting scars at all integration sites then reveals the balance between several repair pathways, which can be linked to the local chromatin state of the integration sites. Here we present a step-by-step protocol to perform DSB-TRIP in K562 cells and to analyse the data by a dedicated computational pipeline. We discuss strengths and limitations of the technique, as well as potential additional applications to study DNA repair.
Genetic Susceptibility Toward Nausea and Vomiting in Surgical Patients
Authors: Gloor Yvonne , Czarnetzki Christoph , Curtin François , Gil-Wey Béatrice , Tramèr Martin R. , Desmeules Jules A.
Published: January 2022

Postoperative nausea and vomiting (PONV) are frequently occurring adverse effects following surgical procedures. Despite predictive risk scores and a pallet of prophylactic antiemetic treatments, it is still estimated to affect around 30% of the patients, reducing their well-being and increasing the burden of post-operative care. The aim of the current study was to characterize selected genetic risk factors of PONV to improve the identification of at risk patients. We genotyped 601 patients followed during the first 24 h after surgery for PONV symptoms in the absence of any antiemetic prophylaxis. These patients were recruited in the frame of a randomized, placebo controlled clinical study aiming to test the efficacy of dexamethasone as a treatment of established PONV. We examined the impact of selected single nucleotide polymorphisms (SNPs) located around 13 different genes and the predicted activity of 6 liver drug metabolizing enzymes from the cytochromes P450 family (CYP) on the occurrence and recurrence of PONV. Our genetic study confirms the importance of genetic variations in the type 3B serotonin receptor in the occurrence of PONV. Our modelling shows that integration of rs3782025 genotype in preoperative risk assessments may help improve the targeting of antiemetic prophylaxis towards patients at risk of PONV.
Polymorphic Membrane Protein 17G of Chlamydia psittaci Mediated the Binding and Invasion of Bacteria to Host Cells by Interacting and Activating EGFR of the Host
Authors: Li Xiaohui , Zuo Zonghui , Wang Yihui , Hegemann Johannes H. , He Cheng
Published: January 2022

Chlamydia psittaci (C. psittaci) is an obligate intracellular, gram-negative bacterium, and mainly causes systemic disease in psittacine birds, domestic poultry, and wild fowl. The pathogen is threating to human beings due to closely contacted to employees in poultry industry. The polymorphic membrane proteins (Pmps) enriched in C. psittaci includes six subtypes (A, B/C, D, E/F, G/I and H). Compared to that of the 1 pmpG gene in Chlamydia trachomatis (C. trachomatis), the diverse pmpG gene-coding proteins of C. psittaci remain elusive. In the present study, polymorphic membrane protein 17G (Pmp17G) of C. psittaci mediated adhesion to different host cells. More importantly, expression of Pmp17G in C. trachomatis upregulated infections to host cells. Afterwards, crosstalk between Pmp17G and EGFR was screened and identified by MALDI-MS and Co-IP. Subsequently, EGFR overexpression in CHO-K1 cells and EGFR knockout in HeLa 229 cells were assessed to determine whether Pmp17G directly correlated with EGFR during Chlamydial adhesion. Finally, the EGFR phosphorylation was recognized by Grb2, triggering chlamydial invasion. Based on above evidence, Pmp17G possesses adhesive property that serves as an adhesin and activate intracellular bacterial internalization by recognizing EGFR during C. psittaci infection
Evaluation of the Updated Diagnostic Criteria for Paraneoplastic Neurologic Syndromes in China
Authors: Cai Meng-Ting , Qiao Song , Lai Qi-Lun , Zheng Yang , Yang Fan , Fang Gao-Li , Shen Chun-Hong , Zhang Yin-Xi , Ding Mei-Ping
Published: January 2022

Background

Recently, the paraneoplastic neurologic syndrome (PNS) diagnostic criteria have received a major update with a new score system over the past 16 years. We aimed to evaluate the diagnostic performance and clinical utility in China.

Methods

An eligible cohort of 113 Chinese patients diagnosed with PNSs from the Second Affiliated Hospital School of Medicine Zhejiang University and published data were enrolled retrospectively. Data including clinical phenotype, antibody type, the presence of cancer, and duration of follow-up were reviewed and re-evaluated to classify the diagnostic levels for the 2004 and 2021 PNS criteria. The performances of these 2 criteria were compared. The critical parameters of antibody and cancer for the updated criteria were further explored.

Results

The cohort consisted of 69 males and 44 females with a median age of 60 years. Limbic encephalitis (23, 20.4%), anti-Hu antibody (32, 28.3%), and small-cell lung cancer (32, 28.3%) were the most common clinical phenotype, detected antibody, and concomitant cancer, respectively. A total of 97 (85.8%) patients were diagnosed with definite PNS according to the 2004 criteria: only 42.3% (41/97) fulfilled the 2021 criteria, while the remaining 40, 14, and 2 re-diagnosed with probable PNS, possible PNS, and non-PNS. The requirement of cancers consistent with antibody and phenotype increased the specificity and thus greatly enhanced the accuracy of the 2021 criteria.

Conclusion

The updated criteria for PNS emphasized the consistency between cancer phenotype and antibody and showed a better diagnostic value. A better diagnostic yield could benefit disease management.
Case Report: Sarcoid-Like Reactions and Tertiary Lymphoid Structures Following Dual Checkpoint Inhibition in a Patient with Early-Stage Lung Adenocarcinoma
Authors: Zhao Xiaoliang , Yue Dongsheng , Qian Juanjuan , Zhang Lei , Song Jin , Zhang Bin , Zhang Chunmei , Sun Leina , Ma Yuchen , Zhang Henghui , Wang Changli
Published: January 2022

Immune checkpoint inhibitor-induced sarcoid-like reactions and tertiary lymphoid structures (TLSs) are increasingly recognized but rarely reported in the same patient. We report a patient with lung adenocarcinoma who displayed sarcoid-like reactions in intrathoracic lymph nodes and tertiary lymphoid structures in surgical tumor after neoadjuvant therapy with nivolumab plus ipilimumab. Pathological examination revealed 50% residual tumor cells after treatment, and the CT evaluation of the primary tumor showed a stable disease. The patient experienced a recurrence eight months after surgery. To identify immune correlates of the limited response to immunotherapy, we conducted genomic and transcriptional assays, multiplex immunoassay, and multiplex immunohistochemistry on the pre- and post-immunotherapy tumor, lymph node, and plasma samples. TP53 R181C, KRAS G12C and SMAD4 R361H were identified as driver mutations of the tumor. In addition to abundant infiltrated lymphocytes, immunotherapy induced high levels of inhibitory components in post-treatment tissue samples, especially the FOXP3+ regulatory T cells in tumor and PD-L1 expression in the lymph node. Despite abundant TLSs in the post-treatment tumor, most TLSs were immature. Moreover, increasing levels of circulating checkpoint proteins BTLA, TIM-3, LAG-3, PD-1, PD-L1, and CTLA4 were observed during immunotherapy. Collectively, our observations revealed that high levels of immunosuppressive molecules in tumor, lymph nodes and/or in peripheral blood might indicate poor outcomes after immunotherapy, even in the setting of a patient with concurrent sarcoid-like reactions and tertiary lymphoid structures.
Successful Induction of Specific Immunological Tolerance by Combined Kidney and Hematopoietic Stem Cell Transplantation in HLA-Identical Siblings
Authors: Fehr Thomas , Hübel Kerstin , de Rougemont Olivier , Abela Irene , Gaspert Ariana , Güngör Tayfun , Hauri Mathias , Helmchen Birgit , Linsenmeier Claudia , Müller Thomas , Nilsson Jakob , Riesterer Oliver , Scandling John D. , Schanz Urs , Cippà Pietro E.
Published: January 2022

Induction of immunological tolerance has been the holy grail of transplantation immunology for decades. The only successful approach to achieve it in patients has been a combined kidney and hematopoietic stem cell transplantation from an HLA-matched or -mismatched living donor. Here, we report the first three patients in Europe included in a clinical trial aiming at the induction of tolerance by mixed lymphohematopoietic chimerism after kidney transplantation. Two female and one male patient were transplanted with a kidney and peripherally mobilized hematopoietic stem cells from their HLA-identical sibling donor. The protocol followed previous studies at Stanford University: kidney transplantation was performed on day 0 including induction with anti-thymocyte globulin followed by conditioning with 10x 1.2 Gy total lymphoid irradiation and the transfusion of CD34+ cells together with a body weight-adjusted dose of donor T cells on day 11. Immunosuppression consisted of cyclosporine A and steroids for 10 days, cyclosporine A and mycophenolate mofetil for 1 month, and then cyclosporine A monotherapy with tapering over 9–20 months. The 3 patients have been off immunosuppression for 4 years, 19 months and 8 months, respectively. No rejection or graft-versus-host disease occurred. Hematological donor chimerism was stable in the first, but slowly declining in the other two patients. A molecular microscope analysis in patient 2 revealed the genetic profile of a normal kidney. No relevant infections were observed, and the quality of life in all three patients is excellent. During the SARS-CoV-2 pandemic, all three patients were vaccinated with the mRNA vaccine BNT162b2 (Comirnaty®), and they showed excellent humoral and in 2 out 3 patients also cellular SARS-CoV-2-specific immunity. Thus, combined kidney and hematopoietic stem cell transplantation is a feasible and successful approach to induce specific immunological tolerance in the setting of HLA-matched sibling living kidney donation while maintaining immune responsiveness to an mRNA vaccine (ClinicalTrials.gov: NCT00365846).
Extracellular Vesicles Promote the Formation of Pre-Metastasis Niche in Gastric Cancer
Authors: Tang Diya , Liu Shanshan , Shen Hong , Deng Gongping , Zeng Shan
Published: January 2022

Globally, gastric cancer (GC) ranks fourth in the incidence of malignant tumors. The early clinical manifestations of GC lack specificity. Most patients are already at an advanced stage when they are first diagnosed, and their late progression is mainly due to peritoneal metastasis. A pre-metastatic microenvironment is formed, before the macroscopic tumor metastasis. Extracellular vesicles (EVs) are nanovesicles released by cells into body fluids. Recent studies have shown that EVs can affect the tumor microenvironment by carrying cargos to participate in cell-to-cell communication. EVs derived from GC cells mediate the regulation of the pre-metastasis niche and act as a coordinator between tumor cells and normal stroma, immune cells, inflammatory cells, and tumor fibroblasts to promote tumor growth and metastasis. This review highlights the regulatory role of EVs in the pre-metastatic niche of GC and mulls EVs as a potential biomarker for liquid biopsy.
Identifying COVID-19 Infections From a Vaccinated Population Using Specific IgA Antibody Test
Authors: Cheng Zhangkai J. , Zheng Peiyan , Xue Mingshan , Chen Youpeng , Sun Baoqing
Published: January 2022

We analyzed the serum from COVID-19 patients and vaccinated subjects, and found that the specific IgA titer level could be used to assist COVID-19 diagnosis, especially in China.
Seagrass Meadows Reduce Wind-Wave Driven Sediment Resuspension in a Sheltered Environment
Authors: Contti Neto Nery , Pomeroy Andrew , Lowe Ryan , Ghisalberti Marco
Published: January 2022

Seagrass meadows are prominent in many coastal zones worldwide and significant contributors to global primary production. The large bottom roughness (or canopy) created by seagrass meadows substantially alters near-bed hydrodynamics and sediment transport. In this study, we investigate how a seagrass meadow in a low-energy environment (forced by local winds) modifies near-bed mean and wave-driven flows and assess how this relates to suspended sediment concentration (SSC). A two-week field study was conducted at Garden Island in southwestern Australia, a shallow and sheltered coastal region subjected to large diurnal sea-breeze cycles, typical of many low-energy environments where seagrasses are found. The mean and turbulent flow structure, along with optical estimates of SSC, were measured within both a seagrass canopy and over an adjacent bare bed. Near-bed mean current velocities within the seagrass canopy were on average 35% of the velocity above the canopy. Oscillatory wave velocities were less attenuated than mean current velocities, with near-bed values on average being 83% of those above the canopy. Mean and maximum shear velocities inferred from currents and waves above the canopy frequently exceeded the threshold for sediment resuspension, but no significant variation was observed in the SSC. However, a significant correlation was observed between SSC and bed shear stress estimated using near-bed velocities inside the canopy. When sediment was resuspended, there were substantial differences between the SSCs within and above the canopy layer, with higher levels confined within the canopy. This study demonstrates the importance of measuring near-bed hydrodynamic processes directly within seagrass canopies for predicting the role seagrass meadows play in regulating local rates of sediment resuspension.
Flume Tank Evaluation on the Effect of Liners on the Physical Performance of the Antarctic Krill Trawl
Authors: Tang Hao , Nsangue Bruno Thierry Nyatchouba , Pandong Achille Njomoue , He Pingguo , Liuxiong Xu , Hu Fuxiang
Published: January 2022

The Antarctic krill (Euphausia superba) is one of the most abundant resources in the ocean, which provides food for several important species in the Antarctic Ocean, and is targeted commercially by humans for many decades. To sustainably manage and harvest the species, energy-efficient, catch-efficient, and selective fishing gears should be developed for the Antarctic krill trawl fishery. This study investigates the effect of twine area and the liner length on the engineering performance of trawl through flume tank testing of trawl model to predict the performance of the full-scale midwater trawl used in the Antarctic krill fishery. Four 1/35th scale trawl model nets with varying lengths of the liner, based on the traditional trawl used in the Antarctic krill fishery, were designed using modified Tauti’s law and were tested in a flume tank at different towing speed, door spread, heavy bob weight, and the ratio of buoyancy to the fishing line (F/G). The results showed that the reduction in liner length by 25 and 50% from the traditional trawl net led to the decrease in twine area by 11.01 and 19.31% and, consequently, resulted in reductions in the lower bridle tension by 12.44 and 19.78%, and increases in energy efficiency by 17.98 and 25.73%, respectively. In addition, the reduction in liner length by 25 and 50% were found to increase the net mouth opening by 2.63 and 5.38% and the swept area by 6.52 and 8.38%, respectively, both of which are proportional to catch rates. Although the trawl net with 50% liner length is more energy-efficient and large mouth opening than those of the trawl net with the liner length over 75% of the trawl body, the large mesh section without a liner can result in the escape of the krill from the trawl, reducing overall catch efficiency. We, therefore, recommend the trawl with 75% of liner length as a suitable design for Antarctic krill considering energy efficiency and catch efficiency.
Characterization of Microbiomes Associated With the Early Life Stages of Sea Cucumber Apostichopus japonicus Selenka
Authors: Yu Juanwen , Sakai Yuichi , Mino Sayaka , Sawabe Tomoo
Published: January 2022

There is a lot of evidence indicating pioneer microbes in early life having various effects on later host biology. Because of the influential phylogenetic position of sea cucumber, which is a deep branching clade in Deuterostomia, the attention on the microbiome in sea cucumber has been increasing. Although microbes in sea cucumber have been reported in several studies, there is a lack of knowledge regarding the pioneer microbiota in the early life stages of sea cucumber. In this study, microbiota changes during the larval development of sea cucumber were assessed using a laboratory rearing system. Microbial community structure was likely to be related to the developmental stage and significant alterations were detected in the late auricularia stage. The relative abundances of Oceanospirillales, Alteromonadales, and Rhodobacterales significantly varied after gut formation. A total of 257 strains were isolated from larval developmental stages of sea cucumber and affiliated to 124 ASVs in the metagenomic analysis. This data demonstrates for the first-time dynamic changes of sea cucumber microbiota in the developmental stages in early life.
Preclinical Pharmacokinetics and Dosimetry of an 89Zr Labelled Anti-PDL1 in an Orthotopic Lung Cancer Murine Model
Authors: Krache Anis , Fontan Charlotte , Pestourie Carine , Bardiès Manuel , Bouvet Yann , Payoux Pierre , Chatelut Etienne , White-Koning Melanie , Salabert Anne-Sophie
Published: January 2022

Anti-PDL1 is a monoclonal antibody targeting the programmed death-cell ligand (PD-L1) by blocking the programmed death-cell (PD-1)/PD-L1 axis. It restores the immune system response in several tumours, such as non-small cell lung cancer (NSCLC). Anti-PDL1 or anti-PD1 treatments rely on PD-L1 tumoural expression assessed by immunohistochemistry on biopsy tissue. However, depending on the biopsy extraction site, PD-L1 expression can vary greatly. Non-invasive imaging enables whole-body mapping of PD-L1 sites and could improve the assessment of tumoural PD-L1 expression.

Methods

Pharmacokinetics (PK), biodistribution and dosimetry of a murine anti-PDL1 radiolabelled with zirconium-89, were evaluated in both healthy mice and immunocompetent mice with lung cancer. Preclinical PET (μPET) imaging was used to analyse [89Zr]DFO-Anti-PDL1 distribution in both groups of mice. Non-compartmental (NCA) and compartmental (CA) PK analyses were performed in order to describe PK parameters and assess area under the concentration-time curve (AUC) for dosimetry evaluation in humans.

Results

Organ distribution was correctly estimated using PK modelling in both healthy mice and mice with lung cancer. Tumoural uptake occurred within 24 h post-injection of [89Zr]DFO-Anti-PDL1, and the best imaging time was at 48 h according to the signal-to-noise ratio (SNR) and image quality. An in vivo blocking study confirmed that [89Zr]DFO-anti-PDL1 specifically targeted PD-L1 in CMT167 lung tumours in mice. AUC in organs was estimated using a 1-compartment PK model and extrapolated to human (using allometric scaling) in order to estimate the radiation exposure in human. Human-estimated effective dose was 131 μSv/MBq.

Conclusion

The predicted dosimetry was similar or lower than other antibodies radiolabelled with zirconium-89 for immunoPET imaging.
Reduced Risk of Sepsis and Related Mortality in Chronic Kidney Disease Patients on Xanthine Oxidase Inhibitors: A National Cohort Study
Authors: Yang Huang-Yu , Hsu Yun-Shiuan Olivia , Lee Tao Han , Wu Chao-Yi , Tsai Chung-Ying , Chou Li-Fang , Tu Hui-Tzu , Huang Yu-Tung , Chang Shang-Hung , Yen Chieh-Li , Hsieh Meng-Hsuan , Lee Cheng-Chia , Kuo George , Hsiao Chih-Yen , Lin Hsing-Lin , Chen Jia-Jin , Yen Tzung-Hai , Chen Yung-Chang , Tian Ya-Chong , Yang Chih-Wei , Anderson Gerard F.
Published: January 2022

Background

Advanced chronic kidney disease (CKD) patients are at higher risk of sepsis-related mortality following infection and bacteremia. Interestingly, the urate-lowering febuxostat and allopurinol, both xanthine oxidase inhibitors (XOis), have been suggested to influence the sepsis course in animal studies. In this study, we aim to investigate the relationship between XOis and infection/sepsis risk in pre-dialysis population.

Methods

Pre-dialysis stage 5 CKD patients with gout were identified through the National Health Insurance Research Database (NHIRD) in Taiwan from 2012 to 2016. Outcomes were also compared with national data.

Results

In our nationwide, population-based cohort study, 12,786 eligible pre-dialysis stage 5 CKD patients were enrolled. Compared to non-users, febuxostat users and allopurinol users were associated with reduced sepsis/infection risk [hazard ratio (HR), 0.93; 95% confidence interval (CI), 0.87–0.99; P = 0.0324 vs. HR, 0.92; 95% CI, 0.86–0.99; P = 0.0163]. Significant sepsis/infection-related mortality risk reduction was associated with febuxostat use (HR, 0.68; 95% CI, 0.52–0.87). Subgroup analysis demonstrated preference of febuxostat over allopurinol in sepsis/infection-related mortality among patients younger than 65 years of age, stain users, non-steroidal anti-inflammatory drug non-users, and non-diabetics. There was no significant difference in major adverse cardiac and cerebrovascular event (MACCE) risk between users and non-users while reduced risk of all-cause mortality was observed for XOi users.

Conclusions

Use of XOi in pre-dialysis stage 5 CKD patients may be associated with reduced risk of sepsis/infection and their related mortality without increased MACCE and overall mortality.
Viral Load in COVID-19 Patients: Implications for Prognosis and Vaccine Efficacy in the Context of Emerging SARS-CoV-2 Variants
Authors: Silva Severino Jefferson Ribeiro da , Lima Suelen Cristina de , Silva Ronaldo Celerino da , Kohl Alain , Pena Lindomar
Published: January 2022

The worldwide spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an unprecedented public health crisis in the 21st century. As the pandemic evolves, the emergence of SARS-CoV-2 has been characterized by the emergence of new variants of concern (VOCs), which resulted in a catastrophic impact on SARS-CoV-2 infection. In light of this, research groups around the world are unraveling key aspects of the associated illness, coronavirus disease 2019 (COVID-19). A cumulative body of data has indicated that the SARS-CoV-2 viral load may be a determinant of the COVID-19 severity. Here we summarize the main characteristics of the emerging variants of SARS-CoV-2, discussing their impact on viral transmissibility, viral load, disease severity, vaccine breakthrough, and lethality among COVID-19 patients. We also provide a rundown of the rapidly expanding scientific evidence from clinical studies and animal models that indicate how viral load could be linked to COVID-19 prognosis and vaccine efficacy among vaccinated individuals, highlighting the differences compared to unvaccinated individuals.