bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Servant Leadership on Job Outcomes: The Mediating Role of Trust in Coworkers
Authors: Rashid Adnan Mahmod M. , Ilkhanizadeh Shiva
Published: July 2022

A good deal of evidence indicates that servant leadership play a critical role in employees' job outcomes. However, research studies on the variables that could mediate the effect of servant leadership in determining this relationship are relatively few. Utilizing the framework of leader-member exchange and social exchange theories, this study examines the mediating effect of “trust in coworkers” in the effect of “servant leadership” on employee job outcomes. Survey data were sourced from 315 bank employees and managers in Northern Cyprus. Partial least square structural equation modeling was utilized with the aid of WarpPLS (7.0) to test the study hypotheses. Servant leadership was found to have a direct and indirect relationship with employees' career satisfaction, service recovery performance, and innovative work behavior. In contrast, the servant leadership relationship with job satisfaction was indirect. In addition, trust in coworkers was found to be a mediator in the relationship between servant leadership and employees' job outcomes. The theoretical and practical implications of this study were highlighted.
Non-pharmacological Management in Palliative Care for Patients With Advanced COPD
Authors: Pyszora Anna , Lewko Agnieszka
Published: July 2022

Chronic obstructive pulmonary disease (COPD) is a disabling condition associated with progressive airflow limitation and lung tissue damage; its main symptoms are breathlessness, fatigue, cough, and sputum production. In the advanced stage of the disease, these symptoms may severely impact on a person's physical and psychological functioning, with some also developing chronic respiratory failure, associated with blood gas abnormalities. Non-pharmacological interventions can improve quality of life and functioning in the management of people living with advanced COPD. This article will provide an overview of common non-pharmacological methods used in the symptomatic management of severe COPD, including: breathlessness and fatigue management strategies, anxiety management, pulmonary rehabilitation (PR) and physical activity (PA), neuromuscular electrical stimulation (NMES), airway clearance techniques (ACTs), nutrition and non-invasive ventilation (NIV). The importance of a holistic and multi-disciplinary approach to people living with COPD will be discussed.
Integrating Character Education Into the RECE Learning Model Through Pancasila and Citizenship Education Subjects
Authors: Sarkadi  , Casmana Asep Rudi , Hisyam Ciek Julyati , Wardatussa'idah Indah
Published: July 2022

This study aimed to investigate teaching character education values using the RECE (reflective, engage, collaborative, and elaborative) model. In Indonesia, Pancasila and Citizenship Education Subjects are mandatory programs that must be incorporated into each activity in schools, either through particular programs or the subjects taught. The civic education module taught in schools has a wider responsibility to teach character education. Currently, this module focuses on theory and encourages students to learn about character. Although teachers can use a wide variety of learning models for teaching character, this study uses a qualitative and descriptive approach focused on exploring the RECE teaching model. This method enables researchers to go to classrooms and observe how teachers impart character education. In total, 15 respondents participated in this study. Of these, three were citizenship education teachers, one was a vice-principal, one was a school principal, and ten were senior high school students in Jakarta. To obtain data, in-depth interviews were used along with 135-min long focus group discussions with all participants. The data were then analyzed using the content analysis method and nVivo software. The results showed that students can reflect, elaborate, collaborate, and communicate well when learning character education in school. The four stages of teaching character education were successful in integrating values in the classroom. This study has implications for the teachers who impart character education.
Pattern and Predictive Factors of Metastasis in Lymph Nodes Posterior to the Right Recurrent Laryngeal Nerve in Papillary Thyroid Carcinoma
Authors: Zhou Mengqian , Duan Yuansheng , Ye Beibei , Wang Yuxuan , Li Hong , Wu Yue , Chen Peng , Zhu Jiajia , Jing Chao , Wu Yansheng , Wang Xudong
Published: July 2022

Objective

The right cervical central lymph nodes include lymph nodes anterior to the right recurrent laryngeal nerve (LN-arRLN) and lymph nodes posterior to the right recurrent laryngeal nerve (LN-prRLN), and are separated by the right recurrent laryngeal nerve (RLN). LN-prRLN is a common site of nodal recurrence after the resection of papillary thyroid carcinoma (PTC). However, the complexity in anatomical structure brings difficulties in determining the surgical scope, so it is necessary to assess the pattern and predictive factors of right cervical central lymph nodes, especially LN-prRLN metastasis in papillary thyroid carcinoma.

Methods

A total of 562 diagnosed PTC patients who underwent right or total thyroidectomy were enrolled in this retrospective study. The clinicopathological features were collected, univariate and multivariate analyses were performed to determine predictive factors of the right central lymph node metastasis.

Results

In this study, the metastatic rates of the right CLN, the LN-arRLN and the LN-prRLN were 59.6% (335/562), 51.8% (291/562) and 30.4% (171/562), respectively. And 22.6% (127/562) of patients had both LN-arRLN and LN-prRLN metastasis. Among patients without LN-arRLN metastasis, the rate of LN-prRLN metastasis was 16.2% (44/271), accounting for 25.7% of the LN-prRLN metastasis group. Factors associated with an increased risk of LN-arRLN metastasis include male, age below 55 years, tumor size > 1cm, extrathyroidal extension (ETE), clinical lymph nodes metastasis(cN1), lateral lymph node metastasis, and left CLN metastasis. In addition, ETE, lateral lymph node metastasis, and LN-arRLN metastasis were independent factors of LN-prRLN metastasis. The predictive factors of LN-prRLN in cN0 PTC were further explored, revealing that tumor size ≥1.5cm, ETE, and LN-arRLN metastasis were independent predictors of LN-prRLN metastasis in cN0 PTC.

Conclusion

The LN-prRLN should not be ignored in surgery because of its high rate of metastasis. Our findings indicate that thorough dissection of central lymph nodes, especially LN-prRLN is crucial in clinical work.
A Highly Selective GSK-3β Inhibitor CHIR99021 Promotes Osteogenesis by Activating Canonical and Autophagy-Mediated Wnt Signaling
Authors: Wang Bo , Khan Saima , Wang Pengtao , Wang Xiaofang , Liu Yangxi , Chen Jingjing , Tu Xiaolin
Published: July 2022

The discovery and application of small molecules is one of the practical strategies of safe osteogenic drugs. The small molecule CHIR99021 (C91) is a highly specific, safe, and most effective GSK-3β Inhibitor. This study found that it efficiently activates the canonical Wnt signaling of bone marrow stromal cell ST2 and promotes osteoblast differentiation and mineralization. C91 increases the production and biochemical activity of osteoblast marker alkaline phosphatase, the expression of osteoblast marker genes Alpl, Bglap, Runx2, and Sp7, and the formation of bone nodules. Triptonide is a transcription inhibitor of Wnt target gene, which diminishes C91-induced osteoblast differentiation in a dose-dependent manner. Meanwhile, C91 also induces autophagy through autophagosome formation and conversion of autophagy biomarker LC-3I into LC-3II. Autophagy inhibitor 3MA partially reduces C91-induced osteoblast differentiation and mineralization; autophagy inducer Rapamycin increases the expression of β-catenin to promote osteogenic differentiation, but cannot alleviate the inhibition of Triptonide on C91-induced osteogenic differentiation, indicating the crosstalk of canonical Wnt signaling and autophagy regulates C91-induced osteoblast differentiation. Furthermore, in order to simulate the in vivo detection of C91 in osteogenesis process, we made a C91 slow-release hydrogel with our newly established polycaprolactone and cell-integrated 3D printing system (PCCI3D module). The sustained release C91 promotes the differentiation and mineralization of ST2 cells. C91 can also enhance the proliferative activity of ST2 cells. The release rate of C91 from hydrogel gradually decreases within 7 days. During this period, the C91 is released by 83.0% and the cell viability maintained at 96.4%. Therefore, the small molecule Wnt agonist C91 promotes osteogenesis through caonical and autophagy-mediated Wnt signaling pathway with an option for translational application.
Behavioral Interventions to Attenuate Driven Overeating and Weight Regain After Bariatric Surgery
Authors: Ames Gretchen E. , Koball Afton M. , Clark Matthew M.
Published: July 2022

Weight regain after bariatric surgery is associated with problematic eating behaviors that have either recurred after a period of improvement or are new-onset behaviors. Problematic eating behaviors after bariatric surgery have been conceptualized in different ways in the literature, such as having a food addiction and experiencing a loss of control of eating. The intersection of these constructs appears to be driven overeating defined as patients’ experiences of reduced control of their eating which results in overeating behavior. The purpose of this review is to define patient experiences of driven overeating through the behavioral expression of emotion-based eating, reward-based eating, and executive functioning deficits—namely impulsivity—which is associated with weight regain after having bariatric surgery. Delineating concepts in this way and determining treatment strategies accordingly may reduce distress related to the inevitable return of increased hunger, cravings, portion sizes, and tolerance for highly palatable foods after surgery. Along with standard behavioral weight maintenance strategies, topics including acceptance, motivation, emotion-based eating, reward-based/impulsive eating, physical activity, and self-compassion are discussed. These concepts have been adapted for patients experiencing weight regain after having bariatric surgery and may be particularly helpful in attenuating driven overeating and weight regain.
The Association Between the Triglyceride-to-High-Density Lipoprotein Cholesterol Ratio and the Risk of Progression to Diabetes From Prediabetes: A 5-year Cohort Study in Chinese Adults
Authors: Sun Yanfei , Wang Zhibin , Huang Zhiqiang , Hu Haofei , Han Yong
Published: July 2022

Objective

Evidence regarding the relationship between the triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-c) ratio and the risk of progression from prediabetes to diabetes remains limited. The purpose of our study was to investigate the relationship between the TG/HDL-C ratio and incident diabetes in prediabetic patients.

Methods

This retrospective cohort study covered 32 regions and 11 cities in China and consecutively and non-selectively collected data from 15,017 patients with prediabetes who had received a health check from 2010 to 2016. Data were obtained from the DATADRYAD database (www.datadryad.org). The Cox proportional-hazards regression model with cubic spline functions and smooth curve fitting (cubic spline smoothing) was used to explore the non-linear relationship between the baseline TG/HDL-c ratio and the risk of diabetes in patients with prediabetes. In addition, we performed a series of sensitivity and subgroup analyses.

Results

The mean age of the included individuals was 50.95 ± 13.48 years, and 9,745 (64.51%) were men. The median (interquartile range) TG/HDL-c ratio was 1.09 (0.69–1.72). During a median follow-up time of 3.05 years, 1,731 (11.46%) patients had a final diagnosis of diabetes. The analysis after adjusting for covariates showed that the TG/HDL-c ratio was positively related to incident diabetes in patients with prediabetes (HR = 1.111, 95% CI 1.061–1.164). Participants with the highest TG/HDL-c ratio (Q4) had higher diabetes incidence rates than those with the lowest TG/HDL-c ratio (Q1) (P < 0.001 for the trend). There was a non-linear relationship between the TG/HDL-c ratio and the risk of diabetes, and the inflection point of the TG/HDL-c ratio was 1.415. The effect sizes (HR) on the left and right sides of the inflection point were 1.336 (95% CI: 1.134–1.573) and 1.055 (95% CI: 0.988–1.126), respectively. The sensitivity analysis demonstrated the robustness of these results.

Conclusion

This study demonstrates a positive, non-linear relationship between the TG/HDL-c ratio and the risk of diabetes in Chinese patients with prediabetes. Aggressive intervention from a treatment perspective is required to lower the TG/HDL-c ratio below the inflection point (1.415) by lowering TG or increasing HDL-c levels.
E-Commerce Logistics System Based on Discrete Dynamic Modeling Analysis
Authors: Meng Gaofei
Published: July 2022

The development of green logistics in a low-carbon environment is an important way for logistics companies to reduce operating costs, and it is also a strategic measure to strengthen the construction of ecological civilization. This study improves the bat algorithm for single-delivery express delivery and multi-delivery, determines the optimal target and seeks the optimal solution, establishes the optimal logistics distribution scheme combined with corporate profits, and finally, compares it with other algorithms to verify the feasibility of the model. In the same experimental environment, it is proven that the performance of the built model is about 20% higher than that of other methods, and the planned path is the most reasonable. In the future application of e-commerce logistics system, it is a more efficient, reasonable, and perfect discrete logistics model.
Metal-Organic Framework Supporting Fe3O4 Prepared by Microwave in Couple With NTP to Eliminate VOCs From Biofuel
Authors: Gao Yan , Cao Qing , Guan Ning , Zhang Zhanchao , Fan Guolan , Dou Huawei , Li Shijie , Wang Qiang , Chen Baoming
Published: July 2022

In the production process of briquette biofuel, terpenes such as pinene and camphene, as well as non-terpenoid VOCs such as formic acid, acetaldehyde, and benzene, are generated during conditioning, drying and other procedures. Different catalysts of Fe3O4 supported by CoFe-ZIFs were prepared by thermal dissolution method and microwave dissolution method with changing the doping amount of iron. The structures of these catalysts were characterized by X-ray Diffraction (XRD), Fourier transform infrared spectrometer Fourier-Transformed InfraRed, thermogravimetric analysis (TG), and scanning electron microscope and the catalytic performance for α-pinene was tested on a fixed bed. The results show that, compared with the thermal dissolution method, the microwave dissolution method was easier to induce iron to form Fe3O4 grains with higher activity. At the same time, the grains did not affect the formation of CoFe-ZIFs structure. Fe3O4 supported on CoFe-ZIFs enhanced the catalytic activity and energy efficiency of the catalysts for α-pinene. Among the test samples, CoFe14-ZIF-W prepared by microwave method with Fe doping 14% mol exhibited the stable structural characteristics and the highest catalytic efficiency of 94.3% and energy efficiency of 8.11 g·kWh−1, which provided a further possibility of practical application for the removal of VOCs from biomass.
When the Eel Meets Dams: Larger Dams’ Long-Term Impacts on Anguilla anguilla (L., 1758)
Authors: Podda Cinzia , Palmas Francesco , Pusceddu Antonio , Sabatini Andrea
Published: July 2022

Diadromous fish, like the European eel Anguilla anguilla (L., 1758), are highly threatened by dams that disrupt river connectivity, consequently impeding fish movements to reach feeding and spawning habitats. In this study, variation in eel occurrence between a historical period (1940–1970) and recent data (2016–2020) was assessed throughout the Sardinian rivers’ network (more than 450 sites). Using Boosted Regression Trees (BRT) we investigated relationships between eel’s occurrence and a set of spatial and temporal environmental variables including a set of dams’ construction features for each period. An overall decrease by 65% of eel’s occurrence was noticed during the ca. 80-years period under scrutiny. Considering a subset (105 and 88 sites for the historical and the recent period, respectively) characterized by the presence of larger dams (height >15 m), eel’s occurrence dropped by 85%. Conversely, eel’s occurrence dropped only by ca. 44% in dam-free sites. During the historical period, eel’s occurrence was mostly affected by time since the initial habitat fragmentation, flow, distance to dams, connectivity, and dams’ height. In the most recent period, eel’s occurrence is mostly affected by dams’ building year, dam-to-sea distance, and, again, dams’ height. Results pinpoint that dams’ construction features and the time from their construction have significant negative effects on eel’s occurrence. Addition of future effective eel restoration practices, apart any other adverse environmental stressor, must consider dams’ removal, wherever socially sustainable or alternatively, the modification of construction features of dams (like excessive height) and the addition of fish ladders.
The Implication of Copula-Based Models for Crop Insurance and Reinsurance Under Systemic Risk
Authors: Sun Yan , Wang Ke
Published: July 2022

The purpose of this paper is to estimate county-level aggregate crop insurance and reinsurance losses under systematic risk. The effect of dependence risk on losses assessment and insurance pricing is quantified by establishing joint distribution functions between county-level yields using different forms of multivariate copulas. The research also stresses the importance of selecting the appropriate copula form for estimating losses. This article highlights several significant findings. The estimated aggregate losses for related counties are not significantly different between the model assuming dependence (copula-based) and the model assuming independence (individual) that adheres to the equivalence principle. On the other hand, the copula-based model has a discernible effect on the estimated Value-at-Risk and Expected Shortfall for related counties. Additionally, for the different layers of the Standard Reinsurance Agreement policy, the copula-based model can measure the aggregate losses more accurately than the individual models. Furthermore, when there is obvious tail dependence in the related counties’ yields, the vine copula function form, which provides a more flexible description of the dependence, is more suitable for quantifying tail risk. As a result, insurers and governments should conduct a more comprehensive risk assessment of yield dependence when rate-making and allocating subsidies.
Can Restoration of Freshwater Mineral Soil Wetlands Deliver Nature-Based Climate Solutions to Agricultural Landscapes?
Authors: Creed Irena F. , Badiou Pascal , Enanga Eric , Lobb David A. , Pattison-Williams John K. , Lloyd-Smith Patrick , Gloutney Mark
Published: July 2022

This study advances scientific understanding of the magnitude of carbon sequestration that could be achieved through conservation (securing existing carbon stocks) and restoration (creating new carbon stocks) of freshwater mineral soil wetlands on agricultural landscapes. Within an agricultural landscape in southern Ontario (Canada), 65,261 wetlands comprising 63,135 ha were lost. Of these, 6,899 wetlands comprising 5,198 ha were “easy-to-restore” wetlands, defined as wetlands that were small (<0.5 ha), with no hydrological inflow or outflow, and that were drained by a drainage ditch and could be restored by plugging the drainage ditch. Within these easy-to-restore wetlands, a chronosequence of wetlands that covered a range of restoration ages [i.e., drained (0 years), 15 years, 25 years, 40 years, and intact marshes] was established to capture potential changes in rates of sedimentation and organic carbon (OC) sequestration with restoration age. Three sediment cores were collected at the center of the open-water portion of the wetland and segmented in the field. In the lab, each individual segment from each core was dried, sieved through a 2-mm mesh, weighed and analyzed for 137Cs and 210Pb radioisotopes and OC. OC stocks (35.60 Mg ha–1) and OC sequestration rates (0.89 Mg C ha–2 yr–1) in wetlands restored for 40 years were comparable to if not marginally larger than intact wetlands, suggesting that restoration promotes OC sequestration but that an initial recovery phase of up to 25 years or more is needed before returning to a pre-drainage equilibrium. An economic analysis to compare the costs and benefits of wetland conservation and restoration was then conducted. The benefit-cost analysis revealed that the financial benefits of carbon sequestration are greater than the financial costs over a 30-year time horizon for retaining wetlands but not for restoring wetlands. The breakeven costs such that wetland restoration is economically feasible based on current carbon price projections is estimated to be $17,173 CAD ha–1 over the 30-year time horizon; any wetland restoration project that costs this amount or less could be justified on economic grounds based solely on the carbon benefits. This study’s findings indicate that wetlands are important nature-based climate solutions, but that incentivizing their use through a carbon market will require either scientific innovations to reduce restoration costs or increase carbon sequestration rates, or stacking carbon benefits with other ecosystem service benefits into a comprehensive market for nature-based climate solutions.
Reviewing the Palaeoenvironmental Record to Better Understand Long-Term Human-Environment Interaction in Inner Asia During the Late Holocene
Authors: Spate Michael , Leipe Christian , Motuzaite Matuzeviciute Giedre
Published: July 2022

The Middle to Late Holocene spread of agropastoralism throughout Eurasia not only subjected domesticated taxa to stressors associated with novel environments but also induced changes in these environments following the introduction of these social-ecological systems. The mountainous region of Inner Asia comprises various steppe, meadow, and forest landscapes where zooarchaeological evidence suggests occupation by herding populations as early as 7,000 years Before Present (BP). Recent archaeobotanical findings indicate the introduction of cropping and the development of agropastoralism around 4,500 BP. Here, we review and synthesize palaeoenvironmental studies and data to examine anthropogenic impacts and modifications of these landscapes. From around 4,000 BP, we find significant changes in palynomorph, charcoal, sediment, and other proxy data, related to the introduction of agriculture to the region, with later intensifications in land use indicators at around 2,000 and 1,000 BP. We note that these impacts are not uniform or continuous through and across the records and may be evidence of shifting phases of occupation and landscape management. This temporal and spatial variability may also be a response to shifts in moisture availability due to long-term Holocene changes in the intensity of the summer monsoon and Westerly circulation systems. Changes in arboreal pollen indicate the development of intensified use of forest resources in the region, which we identify as a topic for future investigation. Based on these data, we stress the long-term human paleoecology in the study area and argue that traditional agropastoralist systems should be considered in future programs of landscape conservation in the region. This study also emphasizes the importance of future local scale multiproxy studies into past anthropogenic changes within the Inner Asian landscape.
A Principal Component Informed Approach to Address Polygenic Risk Score Transferability Across European Cohorts
Authors: Pärna Katri , Nolte Ilja M. , Snieder Harold , Fischer Krista ,   Estonian Biobank Research Team, Marnetto Davide , Pagani Luca
Published: July 2022

One important confounder in genome-wide association studies (GWASs) is population genetic structure, which may generate spurious associations if not properly accounted for. This may ultimately result in a biased polygenic risk score (PRS) prediction, especially when applied to another population. To explore this matter, we focused on principal component analysis (PCA) and asked whether a population genetics informed strategy focused on PCs derived from an external reference population helps in mitigating this PRS transferability issue. Throughout the study, we used two complex model traits, height and body mass index, and samples from UK and Estonian Biobanks. We aimed to investigate 1) whether using a reference population (1000G) for computation of the PCs adjusted for in the discovery cohort improves the resulting PRS performance in a target set from another population and 2) whether adjusting the validation model for PCs is required at all. Our results showed that any other set of PCs performed worse than the one computed on samples from the same population as the discovery dataset. Furthermore, we show that PC correction in GWAS cannot prevent residual population structure information in the PRS, also for non-structured traits. Therefore, we confirm the utility of PC correction in the validation model when the investigated trait shows an actual correlation with population genetic structure, to account for the residual confounding effect when evaluating the predictive value of PRS.
Comprehensive comparative analysis of histopathology and gene expression in subchondral bone between kashin-beck disease and primary osteoarthritis
Authors: Yang Lei , Sun Jingwen , Zhang Ying , Guo Xiong , Zhao Guanghui
Published: July 2022

Kashin-Beck disease (KBD) is an endemic, degenerative osteoarthropathy that exhibits some similar characteristics to osteoarthritis (OA) but with different etiologies and pathogeneses. In addition to cartilage damage, microstructural changes of bone were observed in KBD. This study aimed to comparatively demonstrate the general histopathological changes, transcriptomics, and differentially expressed miRNAs of subchondral bone between KBD and OA. Tibial plateau subchondral bone samples were collected from eighteen patients with KBD and eighteen patients with OA. Histopathological changes were examined by hematoxylin-eosin (HE) staining, safranin O-fast green staining, and picrosirius red staining. RNA sequencing and miRNA array analysis were performed to screen the differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs), respectively. The subchondral bone samples of the tibial plateau of KBD and OA both showed increased thickness and sclerosis. A total of 179 DEGs and 124 DEMs were identified in subchondral bone between KBD and OA, which were involved in several vital GO terms and KEGG signaling pathways. Our results suggest that the pathological mechanisms of subchondral bone are different between KBD and OA, although they exhibit similar histopathological features. Integrated analysis revealed several genes such as ADAMTS14, SLC13A5, and CEACAM1, that may be crucial DEGs in subchondral bone between KBD and OA, suggesting that these genes could serve as potential differential diagnostic biomarkers for subchondral bone lesions in KBD and OA. These findings provide valuable information for further clarifying pathological changes in subchondral bone in KBD and OA.
Identification of pyroptosis-related subtypes, development of a prognostic model, and characterization of tumour microenvironment infiltration in gastric cancer
Authors: Cao Feng , Hu Jingtao , Yuan Hongtao , Cao Pengwei , Cheng Yunsheng , Wang Yong
Published: July 2022

As a new programmed death mode, pyroptosis plays an indispensable role in gastric cancer (GC) and has strong immunotherapy potential, but the specific pathogenic mechanism and antitumor function remain unclear. We comprehensively analysed the overall changes of pyroptosis-related genes (PRGs) at the genomic and epigenetic levels in 886 GC patients. We identified two molecular subtypes by consensus unsupervised clustering analysis. Then, we calculated the risk score and constructed the risk model for predicting prognostic and selected nine PRGs related genes (IL18RAP, CTLA4, SLC2A3, IL1A, KRT7,PEG10, IGFBP2, GPA33, and DES) through LASSO and COX regression analyses in the training cohorts and were verified in the test cohorts. Consequently, a highly accurate nomogram for improving the clinical applicability of the risk score was constructed. Besides, we found that multi-layer PRGs alterations were correlated with patient clinicopathological features, prognosis, immune infiltration and TME characteristics. The low risk group mainly characterized by increased microsatellite hyperinstability, tumour mutational burden and immune infiltration. The group had lower stromal cell content, higher immune cell content and lower tumour purity. Moreover, risk score was positively correlated with T regulatory cells, M1 and M2 macrophages. In addition, the risk score was significantly associated with the cancer stem cell index and chemotherapeutic drug sensitivity. This study revealed the genomic, transcriptional and TME multiomics features of PRGs and deeply explored the potential role of pyroptosis in the TME, clinicopathological features and prognosis in GC. This study provides a new immune strategy and prediction model for clinical treatment and prognosis evaluation.
Multi-organ Immune-Related Adverse Event Is a Risk Factor of Immune Checkpoint Inhibitor-Associated Myocarditis in Cancer Patients: A Multi-center Study
Authors: Xie Xiaohong , Wang Liqiang , Li Yingqing , Xu Yan , Wu Jianhui , Lin Xinqing , Lin Wen , Mai Qicong , Chen Zhanhong , Zhang Jiexia , Xie Zhanhong , Qin Yinyin , Liu Ming , Lu Mingjun , Luo Bihui , Zhou Chengzhi
Published: July 2022

Background and Objective

Immune checkpoint inhibitor (ICI)-associated myocarditis is a fatal immune-related adverse events (irAEs), which is prone to affecting multiple organ systems. Multi-organ irAEs have not been fully studied in ICI-associated myocarditis. Therefore, we aimed to explore the impact of multi-organ irAEs on ICI myocarditis in terms of clinical features, treatment, and prognosis.

Methods

This was a retrospective study. The clinical data of ICI myocarditis patients were collected from 6 hospitals in China. The risk factors and characteristics of pure myocarditis and multi-organ irAEs were analyzed. The overall survival (OS) after myocarditis was analyzed and univariate and multivariate regression analysis were performed.

Results

A total of 46 patients were analyzed in this study. Multi-organ irAEs were common (30/46, 65.2%) and prone to severe heart failure. The severe myocarditis was observed in 32 patients (69.6%). When myocarditis occurred, neutrophil to lymphocyte ratio, C-reactive protein, lactate dehydrogenase, interleukin (IL)-6, IL-10, creatine kinase, MB isoenzyme of creatine kinase, and brain natriuretic peptide increased from baseline, but absolute lymphocyte count decreased. Thymoma (B2/B3) was a risk factor for multi-organ irAEs. Heart failure and myocarditis were more severe in patients with multi-organ irAEs and require early corticosteroid therapy (<24 hours). Univariate analysis showed that age ≥ 60 years, myocarditis (grade 3-4), heart failure (grade 3-4), multi-organ irAEs, and severe myocarditis were associated with OS after myocarditis. After adjusting for other factors, heart failure (grade 3-4) was an independent risk factor for immune-related myocarditis (HR: 6.655, 95% CI: 1.539-28.770, p=0.011).

Conclusion

Patients with ICI-associated myocarditis had multi-organ irAEs with a high incidence of severe myocarditis, mortality, and poor prognosis. Thymoma was prone to those patients with multiple organs involvement. Patients could benefit from early corticosteroid intervention. Heart failure (grade 3-4) was an independent risk factor for OS after myocarditis.
Metabolite profile of COVID-19 revealed by UPLC-MS/MS-based widely targeted metabolomics
Authors: Liu Jun , Li Zhi-Bin , Lu Qi-Qi , Yu Yi , Zhang Shan-Qiang , Ke Pei-Feng , Zhang Fan , Li Ji-Cheng
Published: July 2022

The metabolic characteristics of COVID-19 disease are still largely unknown. Here, 44 patients with COVID-19 (31 mild COVID-19 patients and 13 severe COVID-19 patients), 42 healthy controls (HC), and 42 patients with community-acquired pneumonia (CAP), were involved in the study to assess their serum metabolomic profiles. We used widely targeted metabolomics based on an ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). The differentially expressed metabolites in the plasma of mild and severe COVID-19 patients, CAP patients, and HC subjects were screened, and the main metabolic pathways involved were analyzed. Multiple mature machine learning algorithms confirmed that the metabolites performed excellently in discriminating COVID-19 groups from CAP and HC subjects, with an area under the curve (AUC) of 1. The specific dysregulation of AMP, dGMP, sn-glycero-3-phosphocholine, and carnitine was observed in the severe COVID-19 group. Moreover, random forest analysis suggested that these metabolites could discriminate between severe COVID-19 patients and mild COVID-19 patients, with an AUC of 0.921. This study may broaden our understanding of pathophysiological mechanisms of COVID-19 and may offer an experimental basis for developing novel treatment strategies against it.
SARS-CoV-2-Specific Adaptive Immunity in COVID-19 Survivors With Asthma
Authors: Chen Li , Yue Junqing , Zhang Shengding , Bai Wenxue , Qin Lu , Zhang Cong , Wu Bihao , Li Moxuan , Xu Shuyun , Jiang Qing , Yang Lin , Xu Qingxiu , Zhu Rongfei , Xie Min , Gong Rui
Published: July 2022

Background

Asthma patients potentially have impaired adaptive immunity to virus infection. The levels of SARS-CoV-2-specific adaptive immunity between COVID-19 survivors with and without asthma are presently unclear.

Methods

COVID-19 survivors (patients with asthma n=11, with allergies n=8, and COVID-19 only n=17) and non-COVID-19 individuals (asthmatic patients n=10 and healthy controls n=9) were included. The COVID-19 patients were followed up at about 8 months and 16 months after discharge. The clinical characteristics, lymphocyte subsets, memory T cells, and humoral immunity including SARS-CoV-2 specific antibodies, SARS-CoV-2 pseudotyped virus neutralization assay, and memory B cells were analyzed in these subjects.

Results

The strength of virus-specific T cell response in COVID-19 survivors was positively correlated with the percentage of blood eosinophils and Treg cells (r=0.4007, p=0.0188; and r=0.4435, p=0.0086 respectively) at 8-month follow-up. There were no statistical differences in the levels of SARS-CoV-2-specific T cell response between the COVID-19 survivors with, and without, asthma. Compared to those without asthma, the COVID-19 with asthma survivors had higher levels of SARS-CoV-2-specific neutralizing antibodies (NAbs) at the 8-month follow-up (p<0.05). Moreover, the level of NAbs in COVID-19 survivors was positively correlated with the percentage of Treg and cTfh2 cells (r=0.5037, p=0.002; and r=0.4846, p=0.0141), and negatively correlated with the percentage of Th1 and Th17 cells (r=-0.5701, p=0.0003; and r=-0.3656, p=0.0308), the ratio of Th1/Th2, Th17/Treg, and cTfh1/cTfh2 cell (r=-0.5356, r=-0.5947, r=-0.4485; all p<0.05). The decay rate of NAbs in the COVID-19 survivors with asthma was not significantly different from that of those without asthma at 16-month follow-up.

Conclusion

The level of SARS-CoV-2-specific NAbs in COVID-19 survivors with asthma was higher than that of those without asthma at 8-month follow-up. The SARS-CoV-2-specific T cell immunity was associated with blood eosinophils and Treg percentages. The SARS-CoV-2-specific humoral immunity was closely associated with cTfh2/cTfh1 imbalance and Treg/Th17 ratio. According to the findings, asthmatic patients in COVID-19 convalescent period may benefit from an enhanced specific humoral immunity, which associates with skewed Th2/Th1 and Treg/Th17 immune.
Bibliometrics analysis on the research status and trends of adult-onset Still’s disease: 1921-2021
Authors: Qin Aining , Sun Jing , Gao Chao , Li Chunying
Published: July 2022

Objectives

The aim of this research is to discuss the research status, hotspots, frontiers and development trends in the field of adult-onset Still’s disease (AOSD) based on bibliometrics and visual analysis by CiteSpace software.

Methods

The relevant research articles on AOSD from 1921 to 2021 were retrieved from the Scopus database. CiteSpace software was used to form a visual knowledge map and conduct analysis for the countries/regions, journals, authors, keywords, clusters, research hotspots and frontiers of the included articles.

Results

There were 2,373 articles included, and the number of articles published during 1921-2021 is increasing. The country with the highest number of articles published was Japan (355, 14.96%), followed by the United States (329, 13.86%) and France (215, 9.06%). The author with the highest number of publications is Ansell, Barbara M. (30, 1.26%), and the author with the highest co-citation frequency is Yamaguchi, Masaya (703). Clinical Rheumatology is the journal with the highest publication frequency. The top five cluster groups were “joint”, “differential diagnosis”, “prednisolone”, “methotrexate” and “macrophage activation syndrome”. The diagnosis, treatment and pathogenesis of AOSD form the main research fields, and prognosis and complications are the research hotspots and trends.

Conclusions

The global research field in AOSD has expanded in the past 100 years. The complications and new pathogenesis of AOSD are hotspots in this field and need further study in the future.
Age-Dependent Dispersal and Relatedness in Tiger Sharks (Galeocerdo cuvier)
Authors: McClain Margaret A. , Hammerschlag Neil , Gallagher Austin J. , Drymon J. Marcus , Grubbs R. Dean , Guttridge Tristan L. , Smukall Matthew J. , Frazier Bryan S. , Daly-Engel Toby S.
Published: July 2022

Understanding dispersal in large marine fauna is necessary for conservation, but movement patterns often vary widely by sex and life stage. In sharks, genetic studies have shown evidence of widespread male-biased dispersal, though tagging and tracking studies on the same populations show both sexes using site fidelity, including philopatry, and moving similar distances. We used a suite of microsatellite loci and DNA samples from 362 previously-tagged tiger sharks (Galeocerdo cuvier) in the northwestern Atlantic, including a large number of residential juveniles, to evaluate reproductive dispersal in light of demographic and published tracking data. We found that lumping size classes together resulted in genetic panmixia across sites, but systematic removal of large individuals showed significant population-level differentiation and three separate population clusters among juveniles less than 260 cm total length. Tests for relatedness found that 8.9% of our sample set was composed of first-order related pairs (N = 16), including several full siblings from different litters, a sign of multi-cycle genetic monogamy which carries implications for effective population size. By mapping genetic assignments of juveniles, we identified a signature of fine-scale genetic structure suggesting broad biparental site fidelity to reproductive habitat in the northeast Gulf of Mexico, which is concordant with both genetic and tracking data. Taken together, these findings demonstrate how lumping individuals from different life stages in genetic studies may obscure fine-scale genetic structure, confounding future conservation efforts.
Spatial-Temporal Distribution of Prorocentrum concavum Population in Relation to Environmental Factors in Xincun Bay, a Tropical Coastal Lagoon in China
Authors: Zou Jian , Xie Hang , Zheng Chengzhi , Lu Songhui
Published: July 2022

A harmful benthic Prorocentrum concavum bloom was recorded in August 2018 in Xincun Bay, China, which is the location of a national seagrass nature reserve. Annual ecological surveys have been conducted to study the population dynamics of P. concavum in the benthic community and water column. Seasonal variations in benthic P. concavum abundance were found and the abundances on seagrass and macroalgae in the wet season were 2.5 and 2.82 times higher, respectively, than those in the dry season, although the differences were not statistically significant. The abundance of P. concavum in the water column differed significantly between seasons. The maximum abundances of benthic and planktonic P. concavum were (1.7 ± 0.59) × 106 cells (100 cm2)−1 on Thalassia hemperichii in July and 2.0 × 104 ± 4.7 × 103 cells L−1 in June, respectively. High spatial heterogeneity in P. concavum abundance was observed among five sampling sites. Abundances were significantly higher in seagrass beds than those in macroalgae beds, mangroves, and coral reefs. The abundance of P. concavum at site A (in a seagrass bed and close to a cage-culture area) was 5.6 times higher than that at site D (seagrass bed and distant from the cage-culture area). Planktonic P. concavum showed a similar spatial distribution and presented a maximum density at site A. Moreover, the abundance of benthic P. concavum also showed heterogeneity on host substrates, and the abundance on T. hemperichii was significantly higher than that on sediment. Based on a Spearman’s test, temperature, dissolved organic phosphorus, and dissolved organic nitrogen were the three important factors driving the spatiotemporal distribution of benthic P. concavum in Xincun Bay. Planktonic P. concavum were derived from cells on the substrates and were influenced by concentrations of dissolved oxygen. In conclusion, seagrass beds may be a reservoir of harmful benthic algal blooms in Xincun Bay and the dense cage-culture area provides sufficient organic nutrients for the growth and reproduction of benthic dinoflagellates.
Characterization of the Rate of Injection of Diesel Solenoid Injectors Operated in the Multiple Injection Strategy: A Comparison of the Spray Momentum and Bosch Tube Methods
Authors: Aljohani Bassam S. , Ben Houidi Moez , Du Jianguo , Dyuisenakhmetov Aibolat , Mohan Balaji , AlRamadan Abdullah , Roberts William L.
Published: July 2022

Multiple injection strategies can be used for controlling the heat release rate in an engine, particularly in compression ignition engines. This can mitigate the heat transfer losses and overcome the limitation related to the maximum pressure allowed for a particular engine. Controlling heat release with repetitive injections requires precise characterization of the fuel injection rates. In such a configuration, the injector used should be characterized for its hydraulic delay, rate of injection, and the effect of dwell timing with multiple injections. This study investigates the fuel injection behavior of a high-flow-rate solenoid injector operated with single and double injections. Two characterization methods, the momentum flux, and the Bosch tube are used and compared to investigate their suitability with the multiple injection strategies. Experiments with single injection are conducted by varying the Energizing Timing (ET) from 0.5 up to 2 ms. The tests with multiple injections (i.e., double injections) are conducted with a fixed ET of 0.5 ms, while the dwell times (δt) are varied from 0.1 up to 1 ms. All tests are performed at 500, 1000, 1500, and 2000 bar rail pressures. Depending on the injection pressure, the injector’s needle could not fully close with short dwell times and the injections are merged. The momentum flux method has faster ramp-up and decaying and more oscillations in the quasi-steady-state phase compared to the Bosch tube method. The effective duration of injection is overpredicted with the Bosch tube method. The momentum flux method is demonstrated to be more suitable for measuring the ROI of multiple injection strategies.
Perivascular spaces visible on magnetic resonance imaging predict subsequent delirium in older patients
Authors: Song Quhong , Zhao Yanli , Lin Taiping , Yue Jirong
Published: July 2022

Background

It remains unknown whether perivascular spaces (PVS) are associated with delirium in older hospitalized patients. We aimed to determine the association between magnetic resonance imaging (MRI)-visible PVS and the risk of delirium in a cohort of older patients.

Methods

We consecutively recruited older patients (≥70 years) admitted to the Geriatric Department of West China Hospital between March 2016 and July 2017, and their imaging data within one year before admission were reviewed retrospectively. PVS was rated on axial T2-weighted images in the basal ganglia (BG) and centrum semiovale (CS) using the validated semiquantitative 4-point ordinal scale. Delirium was screened within 24 h of admission and three times daily thereafter, using the confusion assessment method. Binary logistic regression analyses were performed to investigate the associations between PVS and delirium.

Results

Among 114 included patients (mean age 84.3 years, 72.8% male), delirium occurred in 20 (17.5%). In patients with MRI examined within 6 months before admission, CS-PVS was found to be associated with delirium (odds ratio [OR] 3.88, 95% confidence interval [CI] 1.07-14.06, unadjusted; and OR 4.24, 95% CI 1.11-16.28, adjusted for age). The associations were enhanced and remained significant even after full adjustment of covariates (OR 7.16, 95% CI 1.16-44.32, adjusted for age, cognitive impairment, smoking, and Charlson Comorbidity Index). Similarly, the relationships between high CS-PVS and delirium were also strengthened after sequentially adjusting all variables of interest, with OR 4.17 (95% CI 1.04-16.73) in unadjusted model and OR 7.95 (95% CI 1.14-55.28) in fully-adjusted model. Adding CS-PVS to the established risk factors improved the risk reclassification for delirium (continuous net reclassification index 62.1%, P = 0.04; and integrated discrimination improvement 12.5%, P = 0.01).

Conclusions

CS-PVS on MRI acquired 6 months earlier predicts subsequent delirium in older patients and may have clinical utility in delirium risk stratification to enable proactive interventions.