bluuebunny/crossref_metadata_2025 huggingface dataset:
RETHINKING Science Communication Education and Training: Towards a Competence Model for Science Communication
Authors: Fähnrich Birte , Wilkinson Clare , Weitkamp Emma , Heintz Laura , Ridgway Andy , Milani Elena
Published: December 2021

Science communication is at a pivotal stage in its development due to the emergence of digital communication platforms that are not only presenting new opportunities but are also leading to new challenges. In this context, science communicators, who can include scientists, researchers, curators, journalists and other types of content producer, may require new types of preparation and support to engage with multiple audiences, across multiple channels. Despite the increasing need for adequate science communication training, research in the field is sparse and oftentimes refers to single case studies, calling for more comprehensive perspectives on what is needed and what is offered to equip future science communicators with relevant competences to cope with the changing science communication ecosystem. Against this backdrop, this paper takes two approaches, drawing on data from RETHINK, a European project comprising seven countries, Italy, the Netherlands, Poland, Portugal, Serbia, Sweden and the United Kingdom. First, we report on findings from a questionnaire survey completed by 459 science communicators across the seven countries, focusing on how science communicators develop their communication skills, the types of training they have received and the types of training they would like to undertake. Second, we assess exploratory data collected from 13 different science communication degree programs regarding how they seek to embed and consider issues of digital transformation within their curricula. On the basis of both analyses, we will introduce ideas for a competence framework that addresses not only working knowledge and skills but also professional (self-)reflection and the overall mindset and worldviews of students, whilst offering capacity for increased consideration of the role of digital transformation.
The Diagnostic and Prognostic Value of Plasma Galectin 3 in HFrEF Related to the Etiology of Heart Failure
Authors: Lu Qun , Zhang Ruo-Chen , Chen Shu-Ping , Li Tao , Wang Ya , Xue Yan-Bo , Liu Jing , Han Xiu , Su Yi-Dan , Bai Ling , Du Xiao-Jun , Ma Ai-Qun
Published: December 2021

Aim:The aim of present study is to evaluate the diagnostic and prognostic value of plasma galectin 3 (Gal-3) for HF originating from different causes.

Methods:We investigated the plasma levels and expression of Gal-3 in cardiac tissues in two transgenic (TG) strains of mice with cardiomyocyte-restricted overexpression of either β2- adrenergic receptor (β2- AR TG) or Mammalian sterile 20-like kinase 1 (Mst1-TG) in the present study. Additionally, 166 patients suffering from heart failure with reduced ejection fraction (HFrEF) in two hospitals within the Shaanxi province were examined in this study. All these patients were treated according to the Chinese HF guidelines of 2014; subsequently, they were followed up for 50 months, and we analyzed the prediction value of baseline Gal-3 to endpoints in these patients.

Results:Gal-3 was localized in the cytoplasm and nucleus of cardiomyocytes, often formed aggregates in Mst1-TG mice. Extracellular Gal-3 staining was uncommon in Mst1-TG hearts. However, in β2-AR TG mice, although Gal-3 was also expressed in myocardial cells, it was more highly expressed in interstitial cells (e.g., fibroblasts and macrophages). Plasma Gal-3 was comparable between nTG and Mst1-TG mice. However, plasma Gal-3 was higher in β2-AR TG mice than in nTG mice. In the cohort of HFrEF patients, the median plasma Gal-3 concentration was 158.42 pg/mL. All participants were divided into two groups according to Gal-3 levels. Patients with Gal-3 concentrations above the median were older, and had lower plasma hemoglobin, but higher plasma creatinine, tissue inhibitor of metalloproteinases 1 (TIMP-1), left ventricular end systolic diameter (LVESD), left ventricular end-systolic volumes (LVESV) and end-diastolic, as well as left ventricular end-diastolic volumes (LVEDV). Spearman correlation analysis revealed that Gal-3 was positively correlated with TIMP-1 (r= 0.396,P< 0.001), LVESV (r= 0.181,P= 0.020) and LVEDV (r= 0.190,P= 0.015). The 50-month clinical follow-up revealed 43 deaths, 97 unplanned re-hospitalizations, and 111 composite endpoint events. Cox analysis demonstrated that although Gal-3 did not provide any prognostic value in either total-HF subjects or coronary-heart-disease (CHD) patients, it did provide prognostic value in non-CHD patients.

Conclusion:Although plasma Gal-3 is associated with TIMP-1 and echocardiographic parameters, the diagnostic and prognostic value of Gal-3 in HFrEF is determined by the etiology of HF.
Multi-Sequence MRI Registration of Atherosclerotic Carotid Arteries Based on Cross-Scale Siamese Network
Authors: Huang Xiaojie , Mao Lizhao , Wang Xiaoyan , Teng Zhongzhao , Shao Minghan , Gao Jiefei , Xia Ming , Shao Zhanpeng
Published: December 2021

Cardiovascular disease (CVD) is a common disease with high mortality rate, and carotid atherosclerosis (CAS) is one of the leading causes of cardiovascular disease. Multisequence carotid MRI can not only identify carotid atherosclerotic plaque constituents with high sensitivity and specificity, but also obtain different morphological features, which can effectively help doctors improve the accuracy of diagnosis. However, it is difficult to evaluate the accurate evolution of local changes in carotid atherosclerosis in multi-sequence MRI due to the inconsistent parameters of different sequence images and the geometric space mismatch caused by the motion deviation of tissues and organs. To solve these problems, we propose a cross-scale multi-modal image registration method based on the Siamese U-Net. The network uses sub-networks with image inputs of different sizes to extract various features, and a special padding module is designed to make the network available for training on cross-scale features. In addition, to improve the registration performance, a multi-scale loss function under Gaussian smoothing is applied for optimization. For the experiments, we have collected a multi-sequence MRI image dataset from 11 patients with carotid atherosclerosis for a retrospective study. We evaluate our overall architectures by cross-validation on our carotid dataset. The experimental results show that our method can generate precise and reliable results with cross-scale multi-sequence inputs and the registration accuracy can be greatly improved by using the Gaussian smoothing loss function. The DSC of our Siamese structure can reach 84.1% on the carotid data set with cross-size input. With the use of GDSC loss, the average DSC can be improved by 5.23%, while the average distance between fixed landmarks and moving landmarks can be decreased by 6.46%.Our code is made publicly available at: https://github.com/MingHan98/Cross-scale-Siamese-Unet.
Effects of Enhanced External Counterpulsation With Different Sequential Levels on Lower Extremity Hemodynamics
Authors: Zhang Yahui , Zhang Yujia , Wang Yinfen , Xu Xiuli , Jin Jing , Zhang Xiaodong , Zhang Wei , Wei Wenbin , Zhong Chubin , Wu Guifu
Published: December 2021

Objective: This study aimed to investigate acute hemodynamics of lower extremities during enhanced external counterpulsation with a three-level sequence at the hips, thighs, and calves (EECP-3), two-level sequence at the hips and thighs (EECP-2), and single leg three-level sequence (EECP-1).

Methods: Twenty healthy volunteers were recruited in this study to receive a 45-min EECP intervention. Blood flow spectrums in the anterior tibial artery, posterior tibial artery, and dorsalis pedis artery were imaged by Color Doppler ultrasound. Mean flow rate (FR), area, pulsatility index (PI), peak systolic velocity (PSV), end-diastolic velocity (EDV), mean flow velocity (MV), and systolic maximum acceleration (CCAs) were sequentially measured and calculated at baseline during EECP-3, EECP-1, and EECP-2.

Results: During EECP-3, PI, PSV, and MV in the anterior tibial artery were significantly higher, while EDV was markedly lower during EECP-1, EECP-2, and baseline (all P < 0.05). Additionally, ACCs were significantly elevated during EECP-3 compared with baseline. Moreover, FR in the anterior tibial artery was significantly increased during EECP-3 compared with baseline (P = 0.048). During EECP-2, PI and MV in the dorsalis pedis artery were significantly higher and lower than those at baseline, (both P < 0.05). In addition, FR was markedly reduced during EECP-2 compared with baseline (P = 0.028). During EECP-1, the area was significantly lower, while EDV was markedly higher in the posterior tibial artery than during EECP-1, EECP-2, and baseline (all P < 0.05). Meanwhile, FR of the posterior tibial artery was significantly reduced compared with baseline (P = 0.014).

Conclusion: Enhanced external counterpulsation with three-level sequence (EECP-3), EECP-2, and EECP-1 induced different hemodynamic responses in the anterior tibial artery, dorsalis pedis artery, and posterior tibial artery, respectively. EECP-3 acutely improved the blood flow, blood flow velocity, and ACCs of the anterior tibial artery. In addition, EECP-1 and EECP-2 significantly increased the blood flow velocity and peripheral resistance of the inferior knee artery, whereas they markedly reduced blood flow in the posterior tibial artery.
Assessment of the CHA2DS2-VASc Score for the Prediction of Death in Elderly Patients With Coronary Artery Disease and Atrial Fibrillation
Authors: Wu Yangxun , Wang Guanyun , Dong Lisha , Qin Liu'an , Li Jian , Yan Hengming , Guo Wenjie , Feng Xiaodong , Zou Yuting , Wang Ziqian , Du Rina , Zhang Yuxiao , Ma Jing , Yin Tong
Published: December 2021

Purpose: Coronary artery disease (CAD) and atrial fibrillation (AF) often coexist and lead to a much higher risk of mortality in the elderly population. The aim of this study was to investigate whether the CHA2DS2-VASc score could predict the risk of death in elderly patients with CAD and AF.

Methods: Hospitalized patients aged ≥65 years with a diagnosis of CAD and AF were recruited consecutively. Patients were divided into 5 groups according to the CHA2DS2-VASc score (≤2, =3, =4, =5, and ≥6). At least a 1-year follow-up was carried out for the assessment of all-cause death.

Results: A total of 1,579 eligible patients were recruited, with 582 all-cause deaths (6.86 per 100 patient-years) occurring during a follow-up of at least 1 year. With the increase in the CHA2DS2-VASc score, the 1-year and 5-year survival rate decreased (96.4% vs. 95.7% vs. 94.0% vs. 86.5% vs. 85.7%, respectively, P < 0.001; 78.4% vs. 68.9% vs. 64.6% vs. 55.5% vs. 50.0%, respectively, P < 0.001). Compared with the patients with CHA2DS2-VASc score <5, for patients with CHA2DS2-VASc score ≥5, the adjusted hazard ratio for death was 1.78 (95% CI: 1.45–2.18, P < 0.001). The predictive values of the CHA2DS2-VASc score ≥5 for in-hospital (C-index = 0.66, 95% CI: 0.62–0.69, P < 0.001), 1-year (C-index = 0.65, 95% CI: 0.63–0.67, P < 0.001) and 5-year (C-index = 0.60, 95% CI: 0.59–0.61, P < 0.001) death were in comparable.

Conclusion: In elderly patients with concomitant CAD and AF, the CHA2DS2-VASc score can be used to predict death with moderate accuracy.
Evolutions of Oil Generation and Expulsion of Marine-Terrestrial Transitional Shales: Implications From a Pyrolysis Experiment on Water-Saturated Shale Plunger Samples
Authors: Fan Qizhang , Cheng Peng , Xiao Xianming , Gai Haifeng , Zhou Qin , Li Tengfei , Gao Ping
Published: December 2021

Shale reservoirs are characterized by self-generation and self-accumulation, and the oil generation and expulsion evolution model of organic-rich shales is one of important factors that obviously influence the enrichment and accumulation of shale oil and gas resources. At present, however, relevant studies on marine-terrestrial transitional shales are inadequate. In this study, a pyrolysis experiment was performed on water-saturated marine-terrestrial transitional shale plunger samples with type Ⅱb kerogen to simulate the evolutions of oil generation and expulsion. The results indicate that marine-terrestrial transitional shales have wider maturity ranges of oil generation and expulsion than marine and lacustrine shales, and the main stages of oil expulsion are later than those of oil generation, with corresponding Ro values of 0.85%–1.15% and 0.70%–0.95%, respectively. Although the oil generation and expulsion process induced a fractionation in compositions between the expelled and retained oils, both the expelled and retained oils of marine-terrestrial transitional shales are dominated by heavy compositions (resins and asphaltenes), which significantly differs from those of marine and lacustrine shales. The kerogen of marine-terrestrial transitional shales initially depolymerized to transitional asphaltenes, which further cracked into hydrocarbons, and the weak swelling effects of the kerogen promoted oil expulsions. The oil generation and expulsion evolutions of these shales are largely determined by their organic sources of terrigenous higher organisms. This study provides a preliminary theoretical basis to reveal the enrichment mechanism of marine-terrestrial transitional shale oil and gas resources.
Techno Commercial Analysis of Liquefied Petroleum Gas Recovery From Natural Gas Using Aspen HYSYS
Authors: Ali Usman , Zafar Muhammad , Ahmed Ashfaq , Zaman Hafiz Kamran , Razzaq Abdul , Daood Syed Sheraz , Bashir Muhammad , Park Young-Kwon
Published: December 2021

Liquefied petroleum gas is an alternative, relatively clean and a supreme source of energy, which is being used as a key component in the global energy supply. The international trade agreements and the chemical and non-chemical demand of liquefied petroleum gas with the increase in the world’s population have brought its production from the processing of natural gas to the limelight. During its processing, a variety of different components are extracted from it, including methane and ethane which remains in the bulk as natural gas. The objective of this research work is to find the capability of investigating the liquefied petroleum gas recovery performance to make the process economical by saving the processing cost and energy. The novelty of this work is to deal with the design and simulation of a liquefied petroleum gas plant using Aspen HYSYS. To make this process energy efficient and economical, different schemes of process alternatives were applied by reducing the sizes of the exchanger and other pieces of equipment. Three cases are studied in which feed is precooled by rerouting the stream and/or by repositioning of the chiller for the recovery of liquefied petroleum gas from natural gas by analyzing their cost and process parameters. The modelling and simulation base case and three different case studies are realized in Aspen HYSYS. It has been observed that case study 2 results in about 10% increase in LPG production where the chiller is repositioned in the separation section of the LPG production flowsheet. Case study 3 shows a maximum decrease in hot side utilities in the flowsheet of about 20% while 10 and 14% decreases are observed for case studies 1 and 2, respectively. Furthermore, economic analysis indicates about 18 and 22% in the capital cost for case studies 2 and 3, respectively, due to the lower size of process units. The outcome of this investigation is to present plenty of suggestions to improve the process efficiency and minimize the requirement to over design the plant components.
Effect of Fin Number and Position on Non-linear Characteristics of Natural Convection Heat Transfer in Internally Finned Horizontal Annulus
Authors: Zhang Kun , Zhang Yu , Wang Xiaoyu , Wang Liangbi
Published: December 2021

Detailed numerical calculations are performed for investigating the effect of fin number and position on unsteady natural convection heat transfer in internally finned horizontal annulus. The SIMPLER algorithm with Quick scheme is applied for solving the Navier Stokes equations of flow and heat transfer. The results show that the heat transfer rate in annulus with fins increases with the increasing numbers of fin and Rayleigh numbers. For Ra = 2 × 105, the effect of numbers of fins and fins position at the bottom part on the unsteady solutions can be neglected, because the self-oscillation phenomenon is mainly affected by natural convection at the upper part of annulus. Although the fin positions cannot increase heat transfer rate significantly in the case of four fins, the self-oscillated solutions can be suppressed by altering fins position.
Identifying Causes of Social Evolution: Contextual Analysis, the Price Approach, and Multilevel Selection
Authors: Thies Christoph , Watson Richard A.
Published: December 2021

Kin selection theory and multilevel selection theory are distinct approaches to explaining the evolution of social traits. The latter claims that it is useful to regard selection as a process that can occur on multiple levels of organisation such as the level of individuals and the level of groups. This is reflected in a decomposition of fitness into an individual component and a group component. This multilevel view is central to understanding and characterising evolutionary transitions in individuality, e.g., from unicellular life to multicellular organisms, but currently suffers from the lack of a consistent, quantifiable measure. Specifically, the two major statistical tools to determine the coefficients of such a decomposition, the multilevel Price equation and contextual analysis, are inconsistent and may disagree on whether group selection is present. Here we show that the reason for the discrepancies is that underlying the multilevel Price equation and contextual analysis are two non-equivalent causal models for the generation of individual fitness effects (thus leaving different “remainders” explained by group effects). While the multilevel Price equation assumes that the individual effect of a trait determines an individual's relative success within a group, contextual analysis posits that the individual effect is context-independent. Since these different assumptions reflect claims about the causal structure of the system, the correct approach cannot be determined on general theoretical or statistical grounds but must be identified by experimental intervention. We outline interventions that reveal the underlying causal structure and thus facilitate choosing the appropriate approach. We note that kin selection theory with its focus on the individual is immune to such inconsistency because it does not address causal structure with respect to levels of organisation. In contrast, our analysis of the two approaches to measuring group selection demonstrates that multilevel selection theory adds meaningful (falsifiable) causal structure to explain the sources of individual fitness and thereby constitutes a proper refinement of kin selection theory. Taking such refined causal structure into account seems indispensable for studying evolutionary transitions in individuality because these transitions are characterised by changes in the selection pressures that act on the respective levels.
Unique Habitat for Benthic Foraminifera in Subtidal Blue Holes on Carbonate Platforms
Authors: Little Shawna N. , van Hengstum Peter J. , Beddows Patricia A. , Donnelly Jeffrey P. , Winkler Tyler S. , Albury Nancy A.
Published: December 2021

Dissolution of carbonate platforms, like The Bahamas, throughout Quaternary sea-level oscillations have created mature karst landscapes that can include sinkholes and off-shore blue holes. These karst features are flooded by saline oceanic waters and meteoric-influenced groundwaters, which creates unique groundwater environments and ecosystems. Little is known about the modern benthic meiofauna, like foraminifera, in these environments or how internal hydrographic characteristics of salinity, dissolved oxygen, or pH may influence benthic habitat viability. Here we compare the total benthic foraminiferal distributions in sediment-water interface samples collected from <2 m water depth on the carbonate tidal flats, and the two subtidal blue holes Freshwater River Blue Hole and Meredith’s Blue Hole, on the leeward margin of Great Abaco Island, The Bahamas. All samples are dominated by miliolid foraminifera (i.e., Quinqueloculina and Triloculina), yet notable differences emerge in the secondary taxa between these two environments that allows identification of two assemblages: a Carbonate Tidal Flats Assemblage (CTFA) vs. a Blue Hole Assemblage (BHA). The CTFA includes abundant common shallow-water lagoon foraminifera (e.g., Peneroplis, Rosalina, Rotorbis), while the BHA has higher proportions of foraminifera that are known to tolerate stressful environmental conditions of brackish and dysoxic waters elsewhere (e.g., Pseudoeponides, Cribroelphidium, Ammonia). We also observe how the hydrographic differences between subtidal blue holes can promote different benthic habitats for foraminifera, and this is observed through differences in both agglutinated and hyaline fauna. The unique hydrographic conditions in subtidal blue holes make them great laboratories for assessing the response of benthic foraminiferal communities to extreme environmental conditions (e.g., low pH, dysoxia).
Association of αENaC p. Ala663Thr Gene Polymorphism With Sudden Sensorineural Hearing Loss
Authors: Chen Jialei , He Jing , Luo Jing , Zhong Shixun
Published: December 2021

Objective: The etiology of sudden sensorineural hearing loss (SSNHL) is still unknown. It has been demonstrated that normal endolymph metabolism is essential for inner ear function and that epithelial sodium channels (ENaC) may play an important role in the regulation of endolymphatic Na+. This study aimed to explore the potential association between αENaC p. Ala663Thr gene polymorphism and SSNHL.

Methods: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to examine the genotype and allele frequency of the αENaC p. Ala663Thr polymorphism in 20 cases of low-frequency SSNHL (LF-SSNHL), 19 cases of high-frequency SSNHL (HF-SSNHL), 31 cases of all frequency SSNHL (AF-SSNHL), 42 cases of profound deafness SSNHL (PD-SSNHL), and 115 normal controls.

Results: The T663 allele was found to be significantly associated with an increased risk of LF-SSNHL (p = 0.046, OR = 2.16, 95% CI = 1.01–4.62). The TT genotype and T663 allele, on the other hand, conferred a protective effect for PD-SSNHL (AA vs. TT: p = 0.012, OR = 0.25, 95% CI = 0.08–0.74; A vs. T: p = 0.001, OR = 0.36, 95% CI = 0.21–0.61). However, there was no statistically significant difference in genotype or allele frequency between the two groups (HF-SSNHL and AF-SSNHL) and the control group.

Conclusion: The αENaC p. Ala663Thr gene polymorphism plays different roles in different types of SSNHL.
Identification and Functional Verification Reveals that miR-195 Inhibiting THRSP to Affect Fat Deposition in Xinyang Buffalo
Authors: Wang Shuzhe , Pan Cuili , Ma Xiaojie , Yang Chaoyun , Tang Lin , Huang Jieping , Wei Xuefeng , Li Hui , Ma Yun
Published: December 2021

The buffalo population is extensive in China, but its meat quality is relatively inferior. Therefore, improving meat quality should be one of the breeding goals. microRNAs (miRNAs) play an essential regulatory role in the post-transcriptional expression of genes. Some studies have reported their function regulating genes related to fat deposition and adipocyte differentiation in cattle, but there is limited reports in buffalo. We performed small RNA transcriptome sequencing of Xinyang buffalo adipose tissue between calves and adults in this study. As a result, 282 mature miRNAs were significantly differentially expressed, and co-expression analysis showed that 454 miRNAs were significantly associated with developmental stages. Target gene identification, GO (gene ontology) annotation, and KEGG analysis of miRNAs showed that miR-195, miR-192, and miR-24-3p could target key genes for lipogenesis and thus regulate adipose deposition and differentiation. Among them, miR-195 was significantly upregulated in adipose tissue and induced adipocytes of adult buffaloes, and its overexpression significantly inhibited lipid accumulation in primary adipocytes. Dual-luciferase reporter gene analysis showed that miR-195 reduced the expression of thyroid hormone response protein (THRSP) by targeting its 3′ untranslated terminal region, suggesting that miR-195 may inhibit lipid accumulation in adipocytes by regulating THRSP. The results confirmed the reliability of predictive screening of miRNAs and provided theoretical support for buffalo fattening.
Application of Mesenchymal Stem Cells During Machine Perfusion: An Emerging Novel Strategy for Organ Preservation
Authors: Li Jiale , Peng Qinbao , Yang Ronghua , Li Kunsheng , Zhu Peng , Zhu Yufeng , Zhou Pengyu , Szabó Gábor , Zheng Shaoyi
Published: December 2021

Although solid organ transplantation remains the definitive management for patients with end-stage organ failure, this ultimate treatment has been limited by the number of acceptable donor organs. Therefore, efforts have been made to expand the donor pool by utilizing marginal organs from donation after circulatory death or extended criteria donors. However, marginal organs are susceptible to ischemia-reperfusion injury (IRI) and entail higher requirements for organ preservation. Recently, machine perfusion has emerged as a novel preservation strategy for marginal grafts. This technique continually perfuses the organs to mimic the physiologic condition, allows the evaluation of pretransplant graft function, and more excitingly facilitates organ reconditioning during perfusion with pharmacological, gene, and stem cell therapy. As mesenchymal stem cells (MSCs) have anti-oxidative, immunomodulatory, and regenerative properties, mounting studies have demonstrated the therapeutic effects of MSCs on organ IRI and solid organ transplantation. Therefore, MSCs are promising candidates for organ reconditioning during machine perfusion. This review provides an overview of the application of MSCs combined with machine perfusion for lung, kidney, liver, and heart preservation and reconditioning. Promising preclinical results highlight the potential clinical translation of this innovative strategy to improve the quality of marginal grafts.
Analyses of circRNA and mRNA Profiles in Vogt–Koyanagi–Harada Disease
Authors: Shu Jia , Su Guannan , Zhang Jun , Liu Zhangluxi , Chang Rui , Wang Qingfeng , Yang Peizeng
Published: December 2021

Recent studies revealed that circular RNAs (circRNAs) are important in numerous biological process and involved in autoimmune diseases. However, their role in Vogt–Koyanagi–Harada (VKH) disease, a classical autoimmune disease, is not yet known. This research aimed to study the expression profile of mRNAs, microRNAs (miRNAs) and circRNAs and investigate the influence of circRNAs on the pathogenesis of VKH disease. We identified circRNAs, miRNAs, and mRNAs expression profiles in CD4+ T cells between 4 VKH patients and 3 healthy controls using the whole-transcriptome sequencing (RNA-seq) technique. We discovered that a total of 5088 mRNAs, 451 circRNAs and 433 miRNAs were differently expressed. The GO and KEGG pathway enrichment analyses were performed for significantly differentially expressed circRNAs and mRNAs. GSEA was conducted for all mRNAs. The functional enrichment suggested that the inflammatory response, the adaptive immune response, NF-kappa B signaling pathway, Th17 cell differentiation, Th1 and Th2 cell differentiation and T cell receptor signaling pathway were associated with VKH disease. In addition, based on the immune-related genes we screened, the circRNA-miRNA-mRNA ceRNA network was analyzed and constructed. Ten differently expressed mRNAs (LAT, ZAP70, ITK, ICOS, RASGRP1, PAG1, PLCG1, PRKCQ, LCK, CARD11) and 5 differently expressed circRNAs (hsa_circ_0033144, hsa_circ_0000233, hsa_circ_0000396, hsa_circ_0001924, hsa_circ_0001320) were selected to be validated by Real-time qPCR (RT-qPCR). The results of RT-qPCR turned out to be consistent with RNA-seq data. Further analysis showed that hsa_circ_0001320 and hsa_circ_0001924 may serve as crucial candidate marker genes of VKH disease. These results reveal that circRNAs may have a crucial immunomodulatory function in the pathophysiological process of VKH disease.
Case Report: Persistent Hypogammaglobulinemia More Than 10 Years After Rituximab Given Post-HSCT
Authors: Luterbacher Fanny , Bernard Fanette , Baleydier Frédéric , Ranza Emmanuelle , Jandus Peter , Blanchard-Rohner Geraldine
Published: December 2021

Rituximab (RTX) is an anti-CD20 monoclonal antibody that targets B cells—from the immature pre-B-cell stage in the bone marrow to mature circulating B cells—while preserving stem cells and plasma cells. It is used to treat autoimmune diseases, hematological malignancies, or complications after hematopoietic stem cell transplantation (HSCT). Its safety profile is acceptable; however, a subset of patients can develop persistent hypogammaglobulinemia and associated severe complications, especially in pediatric populations. We report the unrelated cases of two young men aged 17 and 22, presenting with persistent hypogammaglobulinemia more than 7 and 10 years after treatment with RTX, respectively, and administered after HSCT for hemolytic anemia and Epstein–Barr virus reactivation, respectively. Both patients’ immunological workups showed low levels of total immunoglobulin, vaccine antibodies, and class switched-memory B cells but an increase in naive B cells, which can also be observed in primary immunodeficiencies such as those making up common variable immunodeficiency. Whole exome sequencing for one of the patients failed to detect a pathogenic variant causing a Mendelian immunological disorder. Annual assessments involving interruption of immunoglobulin replacement therapy each summer failed to demonstrate the recovery of endogenous immunoglobulin production or normal numbers of class switched-memory B cells 7 and 10 years after the patients’ respective treatments with RTX. Although the factors that may lead to prolonged hypogammaglobulinemia after rituximab treatment (if necessary) remain unclear, a comprehensive immunological workup before treatment and long-term follow-up are mandatory to assess long-term complications, especially in children.
Characterization of SARS-CoV-2-Specific Humoral and Cellular Immune Responses Induced by Inactivated COVID-19 Vaccines in a Real-World Setting
Authors: Li Ziwei , Xiang Tiandan , Liang Boyun , Deng Hui , Wang Hua , Feng Xuemei , Quan Xufeng , Wang Xiaoyan , Li Sumeng , Lu Sihong , Yang Xuecheng , Wang Baoju , Zelinskyy Gennadiy , Trilling Mirko , Sutter Kathrin , Lu Mengji , Dittmer Ulf , Yang Dongliang , Zheng Xin , Liu Jia
Published: December 2021

While the immunogenicity of inactivated vaccines against coronavirus disease 2019 (COVID‐19) has been characterized in several well-conducted clinical trials, real-world evidence concerning immune responses against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) raised by such vaccines is currently missing. Here, we comprehensively characterized various parameters of SARS-CoV-2-specific cellular and humoral immune responses induced by inactivated COVID-19 vaccines in 126 individuals under real-world conditions. After two doses of vaccination, S-receptor binding domain IgG (S-RBD IgG) and neutralizing antibody (NAb) were detected in 87.06% (74/85) and 78.82% (67/85) of individuals, respectively. Female participants developed higher concentrations of S-RBD IgG and NAb compared to male vaccinees. Interestingly, a longer dosing interval between the first and second vaccination resulted in a better long-term SARS-CoV-2 S-RBD IgG response. The frequencies of CD4+ T cells that produce effector cytokines (IFN-γ, IL-2, and TNF-α) in response to stimulation with peptide pools corresponding to the SARS-CoV-2 spike (S), nucleocapsid (N) or membrane (M) protein were significantly higher in individuals received two doses of vaccine than those received one dose of vaccine and unvaccinated individuals. S, N, or M-specific CD4+ and CD8+ T cell responses were detectable in 95.83% (69/72) and 54.16% (39/72) of double-vaccinated individuals, respectively. The longitudinal analysis demonstrated that CD4+ T cell responses recognizing S, N, and M waned quickly after a single vaccine dose, but were boosted and became more sustained following a second dose. Overall, we provide a comprehensive characterization of immune responses induced by inactivated COVID-19 vaccines in real-world settings, suggesting that both humoral and cellular SARS-CoV-2-specific immunity are elicited in the majority of individuals after two doses of inactivated COVID-19 vaccines.
Evaluation of Cyclooxygenase-2 and p53 Expression in Pterygium Tissue Following Preoperative Intralesional Ranibizumab Injection
Authors: Omar Ahmad Razif , Ibrahim Mohtar , Jaafar Hasnan , Siti-Azrin Ab Hamid , Zunaina Embong
Published: December 2021

Introduction: Overexpression of vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), and p53 are the postulated aetiopathogenesis in pterygium. VEGF is responsible for the induction of COX-2 expression, whereas p53 plays an important role in the regulation of VEGF. This study aimed to evaluate the immunohistochemistry of COX-2 and p53 expressions from excised pterygium tissue from patients who received intralesional ranibizumab (anti-VEGF) injection 2 weeks prior to pterygium surgery.

Materials and Methods: An interventional comparative study involving patients presenting with primary pterygium was conducted between September 2015 and November 2017. The patients were randomized into either the intervention or control group. Patients in the intervention group were injected with intralesional ranibizumab (0.5 mg/0.05 ml) 2 weeks prior to surgery. Both groups underwent pterygium excision followed by conjunctival autograft. Immunohistochemistry staining was performed to evaluate COX-2 and p53 expressions in the excised pterygium tissue.

Results: A total of 50 patients (25 in both the intervention and control groups) were recruited. There were 34 (68%) patients with grade III pterygium and 16 (32%) patients with grade IV pterygium. There was statistically significant difference in reduction of COX-2 expression in the epithelial layer [84.0% (95% CI: 63.9, 95.5)] (p = 0.007) and stromal layer [84.0% (95% CI: 63.9, 95.5)] (p < 0.001) between intervention and control groups. There was no significant difference in the reduction of p53 expression between the two groups.

Conclusion: This study demonstrated the possible use of intralesional anti-VEGF treatment prior to pterygium excision as a potential future modality of adjunctive therapy for pterygium surgery.
Analysis of Risk Factors for Perioperative Acute Kidney Injury and Management Strategies
Authors: Yu Xiang , Feng Zhe
Published: December 2021

Acute kidney injury (AKI) is a serious clinical syndrome, and one of the common comorbidities in the perioperative period. AKI can lead to complications in surgical patients and is receiving increasing attention in clinical workup. In recent years, the analysis of perioperative risk factors has become more in-depth and detailed. In this review, the definition, diagnosis, and pathophysiological characteristics of perioperative AKI are reviewed, and the main risk factors for perioperative AKI are analyzed, including advanced age, gender, certain underlying diseases, impaired clinical status such as preoperative creatinine levels, and drugs that may impair renal function such as non-steroidal anti-inflammatory drugs (NASIDs), ACEI/ARB, and some antibiotics. Injectable contrast agents, some anesthetic drugs, specific surgical interventions, anemia, blood transfusions, hyperglycemia, and malnutrition are also highlighted. We also propose potential preventive and curative measures, including the inclusion of renal risk confirmation in the preoperative assessment, minimization of intraoperative renal toxin exposure, intraoperative management and hemodynamic optimization, remote ischemic preadaptation, glycemic control, and nutritional support. Among the management measures, we emphasize the need for careful perioperative clinical examination, timely detection and management of AKI complications, administration of dexmedetomidine for renal protection, and renal replacement therapy. We aim that this review can further increase clinicians' attention to perioperative AKI, early assessment and intervention to try to reduce the risk of AKI.
Serum Sodium Concentration and Increased Risk for Primary Epiretinal Membrane
Authors: Xue Can Can , Cui Jing , Zhu Xiao Bo , Xu Jie , Zhang Chun , Chen Dong Ning , Wang Ya Xing , Jonas Jost B.
Published: December 2021

Aims: To examine the prevalence of primary epiretinal membranes (ERMs) and associated systemic factors.

Methods: The cross-sectional, community-based Tongren Health Care Study enrolled participants who received regular health examinations in the Beijing Tongren Hospital from 2017 to 2019. Using fundus photographs, retinal specialists assessed the presence of ERMs and their systemic associations.

Results: Primary ERMs were detected in 841/22820 individuals, with a prevalence of 3.7% [95% confidence intervals (CI): 3.4–3.9%] in the total study population (mean age: 44.5 ± 13.8 years) and 6.5% (95% CI: 6.1–7.0%) in individuals aged 40+ years. In multivariable analysis, a higher ERMs prevalence was associated with older age [odds ratio (OR): 1.10; P < 0.001], higher serum cholesterol concentration (OR: 1.14; P = 0.003) and higher serum sodium concentration (SSC) (OR: 1.12; P < 0.001). In women, a higher SSC, even within the normal range, was associated with an increased risk of ERMs (OR: 1.19; P < 0.001). Female participants with an SSC of 144–145mmol/L as compared with those with an SSC of 135–137 mmol/L had a 5-fold increased odds of having ERMs (All women: OR: 5.33; P < 0.001; Women aged 40+years: OR: 4.63; P < 0.001).

Conclusion: Besides older age and higher serum cholesterol concentration, a higher SSC, even if within the normal range, was independently associated with a higher ERM prevalence in women.
Predictors of Prolonged Cardiopulmonary Exercise Impairment After COVID-19 Infection: A Prospective Observational Study
Authors: Vonbank Karin , Lehmann Antje , Bernitzky Dominik , Gysan Maximilian Robert , Simon Stefan , Schrott Andrea , Burtscher Martin , Idzko Marco , Gompelmann Daniela
Published: December 2021

Objectives: Coronavirus disease 2019 (COVID-19) is a global pandemic affecting individuals to varying degrees. There is emerging evidence that even patients with mild symptoms will suffer from prolonged physical impairment.

Methods: In this prospective observational study, lung function, and cardiopulmonary exercise testing have been performed in 100 patients for 3–6 months after COVID-19 diagnosis (post-CoVG). Depending on the severity of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, patients were divided into asymptomatic, or mild to moderate (mild post-CoVG), and severe post-CoVG [hospitalization with or without intensive care unit/non-invasive ventilation (ICU/NIV)]. Results have been compared with age, sex, and body mass index (BMI) matched control group (CG, N = 50).

Results: Both lung function (resting) and exercise capacity (peak workload, Wpeak and peak oxygen uptake, VO2 peak - % predicted) were considerably affected in patients with severe post-CoV (81.7 ± 27.6 and 86.1 ± 20.6%), compared to the mild post-CoVG (104.8 ± 24.0%, p = 0.001 and 100.4 ± 24.8; p = 0.003). In addition, also the submaximal exercise performance was significantly reduced in the severe post-CoVG (predicted VT1/VO2 peak; p = 0.013 and VT2/VO2 peak; p = 0.001). Multiple linear regression analyses revealed that 74 % (adjusted R2) of the variance in relative VO2 peak of patients who had CoV could be explained by the following variables: lower age, male sex, lower BMI, higher DLCO, higher predicted heart rate (HR) peak, lower breathing reserve (BR), and lower SaO2 peak, which were related to higher relative VO2 peak values. Higher NT-proBNP and lower creatinine kinase (CK) values were seen in severe cases compared to patients who experienced mild CoV.

Discussion: Maximal and submaximal exercise performance in patients recovering from severe COVID-19 remain negatively affected for 3–6 months after COVID-19 diagnosis. The presented findings reveal that impaired pulmonary, cardiac, and skeletal muscle function contributed to the limitation of VO2 peak in those patients, which may have important implications on rehabilitation programs.
Altered T-Cell Receptor β-Chain and Lactate Dehydrogenase Are Associated With the Immune Pathogenesis of Biliary Atresia
Authors: Ye Jing , Lai Dengming , Cao Dan , Tan Linhua , Hu Lei , Zha Hua , Yang Jiezuan , Shu Qiang
Published: December 2021

Background: Biliary atresia (BA) is considered to be an autoimmune-mediating inflammatory injury. The pathogenesis of BA has been proposed with the clonal transformation of T cells expressing analogous T-cell receptor β-chain variable regions (TRBVs).

Methods: The TRBV profile of the peripheral blood mononuclear cells (PBMCs) in infants with BA and control infants (healthy donors, HDs), respectively, were characterized by using high-throughput sequencing (HTS). The diversity of T cells was analyzed based on the frequency of complementarity-determining region 3 (CDR3) or V(CDR3)J. Moreover, the correlation between absolute lymphocyte count (ALC) and lactate dehydrogenase (LDH) or diversity (clonality) indices, respectively, were analyzed for subjects with BA and HD.

Results: The diversity indices of CDR3, V(CDR3)J in BA are lower than those in subjects with HD, in addition, there are significantly different levels of neutrophile, neutrophile/lymphocyte ratio (NLR), and LDH between groups of BA and HD. The correlation between ALC and diversity index is significant in subjects with HD but is not for subjects with BA. Conversely, the relationship between ALC and LDH is significant in subjects with BA but is not for subjects with HD. Moreover, 12 CDR3 motifs are deficient or lower expression in BA compared with that in the HD group.

Conclusion: Our results demonstrate that the profile of TRBV repertoire is significantly different between subjects with BA and HD, and suggest that the immune imbalance and elevated LDH level are associated with the pathogenesis of BA. Moreover, the values of neutrophile, NLR, and LDH could be used for the differential diagnosis of BA.
Management of Endothelial Dysfunction in Systemic Sclerosis: Current and Developing Strategies
Authors: Zanin-Silva Djúlio César , Santana-Gonçalves Maynara , Kawashima-Vasconcelos Marianna Yumi , Oliveira Maria Carolina
Published: December 2021

Systemic Sclerosis (SSc) is an autoimmune disease marked by dysregulation of the immune system, tissue fibrosis and dysfunction of the vasculature. Vascular damage, remodeling and inadequate endothelial repair are hallmarks of the disease. Since early stages of SSc, damage and apoptosis of endothelial cells (ECs) can lead to perivascular inflammation, oxidative stress and tissue hypoxia, resulting in multiple clinical manifestations. Raynaud's phenomenon, edematous puffy hands, digital ulcers, pulmonary artery hypertension, erectile dysfunction, scleroderma renal crisis and heart involvement severely affect quality of life and survival. Understanding pathogenic aspects and biomarkers that reflect endothelial damage in SSc is essential to guide therapeutic interventions. Treatment approaches described for SSc-associated vasculopathy include pharmacological options to improve blood flow and tissue perfusion and, more recently, cellular therapy to enhance endothelial repair, promote angiogenesis and heal injuries. This mini-review examines the current knowledge on cellular and molecular aspects of SSc vasculopathy, as well as established and developing therapeutic approaches for improving the vascular compartment.
Development and Validation of a Nomogram Based on 18F-FDG PET/CT Radiomics to Predict the Overall Survival in Adult Hemophagocytic Lymphohistiocytosis
Authors: Yang Xu , Liu Jun , Lu Xia , Kan Ying , Wang Wei , Zhang Shuxin , Liu Lei , Zhang Hui , Li Jixia , Yang Jigang
Published: December 2021

Purpose: Hemophagocytic lymphohistiocytosis (HLH) is a rare and severe disease with a poor prognosis. We aimed to determine if 18F-fluorodeoxyglucose (18F-FDG) PET/CT-derived radiomic features alone or combination with clinical parameters could predict survival in adult HLH.

Methods: This study included 70 adults with HLH (training cohort, n = 50; validation cohort, n = 20) who underwent pretherapeutic 18F-FDG PET/CT scans between August 2016 and June 2020. Radiomic features were extracted from the liver and spleen on CT and PET images. For evaluation of 6-month survival, the features exhibiting p < 0.1 in the univariate analysis between non-survivors and survivors were selected. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to develop a radiomics score (Rad-score). A nomogram was built by the multivariate regression analysis to visualize the predictive model for 3-month, 6-month, and 1-year survival, while the performance and usefulness of the model were evaluated by calibration curves, the receiver operating characteristic (ROC) curves, and decision curves.

Results: The Rad-score was able to predict 6-month survival in adult HLH, with area under the ROC curves (AUCs) of 0.927 (95% CI: 0.878–0.974) and 0.869 (95% CI: 0.697–1.000) in the training and validation cohorts, respectively. The radiomics nomogram combining the Rad-score with the clinical parameters resulted in better performance for predicting 6-month survival than the clinical model or the Rad-score alone. Moreover, the nomogram displayed superior discrimination, calibration, and clinical usefulness in both the cohorts.

Conclusion: The newly developed Rad-score is a powerful predictor for overall survival (OS) in adults with HLH. The nomogram has great potential for predicting 3-month, 6-month, and 1-year survival, which may timely guide personalized treatments for adult HLH.