bluuebunny/crossref_metadata_2025 huggingface dataset:
The mysterious adventures of Detective Duke: How storified programming MOOCs support learners in achieving their learning goals
Authors: Hagedorn Christiane , Serth Sebastian , Meinel Christoph
Published: January 2023

About 15 years ago, the first Massive Open Online Courses (MOOCs) appeared and revolutionized online education with more interactive and engaging course designs. Yet, keeping learners motivated and ensuring high satisfaction is one of the challenges today's course designers face. Therefore, many MOOC providers employed gamification elements that only boost extrinsic motivation briefly and are limited to platform support. In this article, we introduce and evaluate a gameful learning design we used in several iterations on computer science education courses. For each of the courses on the fundamentals of the Java programming language, we developed a self-contained, continuous story that accompanies learners through their learning journey and helps visualize key concepts. Furthermore, we share our approach to creating the surrounding story in our MOOCs and provide a guideline for educators to develop their own stories. Our data and the long-term evaluation spanning over four Java courses between 2017 and 2021 indicates the openness of learners toward storified programming courses in general and highlights those elements that had the highest impact. While only a few learners did not like the story at all, most learners consumed the additional story elements we provided. However, learners' interest in influencing the story through majority voting was negligible and did not show a considerable positive impact, so we continued with a fixed story instead. We did not find evidence that learners just participated in the narrative because they worked on all materials. Instead, for 10–16% of learners, the story was their main course motivation. We also investigated differences in the presentation format and concluded that several longer audio-book style videos were most preferred by learners in comparison to animated videos or different textual formats. Surprisingly, the availability of a coherent story embedding examples and providing a context for the practical programming exercises also led to a slightly higher ranking in the perceived quality of the learning material (by 4%). With our research in the context of storified MOOCs, we advance gameful learning designs, foster learner engagement and satisfaction in online courses, and help educators ease knowledge transfer for their learners.
“Playing jazz is what she does”: The impact of peer identification and mastery experiences on female jazz pupils’ self-efficacy at Improbasen
Authors: Johansen Guro Gravem
Published: January 2023

This article is a conceptual analysis of the concepts of enactive mastery experience and vicarious learning experience from Albert Bandura’s socio-cognitive theory, applied to the empirical case of the Norwegian learning centre Improbasen. I outline some historical and socio-psychological contexts that posits jazz practice as a masculine stereotyped activity, to indicate various mechanisms that may cause a low self-efficacy for playing jazz in girls and non-binary children. When presenting the empirical case, I highlight the learning center’s strategies to promote gender equality. Finally, I discuss theoretically how these strategies may strengthen self-efficacy in children, relating them to experiences of mastery and vicarious learning. In conclusion I suggest that a diverse learning environment that facilitates peer identification works better for all genders than, when iconic male jazz musicians are treated as models for learning.
Giftedness and gifted education: A systematic literature review
Authors: Baccassino Francesca , Pinnelli Stefania
Published: January 2023

The present study aims to discuss the state of the art inherent in pedagogical-didactic research on the education of gifted students. To this end, a systematic review of scientific texts published between 2011 and 2021 was carried out. The present article is organized as follows: introduction to the topic; definition of the objectives, research questions, and methodological protocol; selection, evaluation, and synthesis of the abstract studies; discussion and evaluation of the results; and conclusions. Multiple tools for identifying the gifted students (for use by psychologists, pedagogists, educators, and teachers) emerge from the findings of the present study. The texts highlight numerous instructional and educational programming models for gifted students in all school grades. The main model is the SEM—(Schoolwide Enrichment Model). The present review shows a conspicuous production on gifted education, with the predominance of recently published articles (indicative of vivid interest in the topic) and of American origin. This geographic predominance, which does not cover the European and eastern parts of the world, may depend on the fact that the databases used [Scopus and Web of Science (WoS)] select results based on the use of English. This review reveals gaps and emerging trends in gifted education research, suggesting possibilities and future perspectives.
A unified decentralized framework for isolated interlinking converters of hybrid DC/AC microgrids
Authors: Li Yue , Yang Pengcheng , Peng Yonggang , Weng Chudi , Sun Jing , Shen Haijiang , Xia Yanghong , Wei Wei
Published: January 2023

Due to the advantages of effectively integrating diversified loads and renewable sources, hybrid DC/AC microgrids have attracted the common attention of industry and academia. Meanwhile, with the increasing number of power electronic devices connected to the system, the complexity of the system increases, which puts forward higher requirements for galvanic isolation and intelligent control methods. This study proposes a unified decentralized framework for isolated interlinking converters (IICs) in hybrid DC/AC microgrids, which include topology and a control strategy to solve the aforementioned problems. Firstly, in terms of topology, a dual active bridge (DAB) converter is adopted to realize galvanic isolation and DC voltage conversion, which can facilitate the interconnection of DC microgrids or be combined with VSC for the interconnection of DC and AC microgrids. Secondly, in terms of the control strategy, a bidirectional voltage–supporting control strategy is proposed for IICs, in which the frequency and voltage are adopted as the indications to balance the power and strengthen the inertia interaction of microgrids. Furthermore, with the proposed control strategy, the voltage sources of different microgrids can share the power fluctuation, cooperatively. The stability of the proposed strategy is analyzed, and the effectiveness is verified by several HIL experiments.
Computational fluid dynamics simulation of cryogenic safety analysis in an liquefied natural gas powered ship during liquefied natural gas leakage
Authors: Wang Zhaowen , Zhang Qipeng , Wang Yi , Li Xin , Zhou Jiong
Published: January 2023

LNG is considered a promising alternative fuel for the marine industry with the increasingly strict environmental requirements while the safety problems caused by LNG leakage accidents need to be concerned and analyzed. In this article, the cryogenic safety analysis of the fuel gas preparation room in an LNG-powered ship during LNG leakage accidents was performed by CFD simulations. The simulation results showed as follows: the range of cryogenic region in the fuel gas preparation room was related to flow field direction during LNG leakage; The surface temperature of equipment dropped to some extent during LNG leakage accidents. The temperature drop was less than 15°C, which was confirmed to be a safe temperature range in engineering; In addition, for safety operation analysis, the NG distribution situation of dangerous regions with explosive limit was also obtained.
Hierarchical entropy analysis for flow pattern of steam-liquid two phase flow in a rod bundle
Authors: Zhang Chao , Liu Xinyue , Hou Yandong , Li Weichao , Cai Benan , Cai Weihua
Published: January 2023

Flow pattern is very key parameter in the study of flow characteristics and heat transfer characteristics of two-phase flow. In this Paper, two-phase boiling experiment in a 3×3 rod bundle was conducted within the following parameter range: 0≤G≤600kg/(m2⋅s),0.1≤p≤0.12MPa,10≤ΔTsub≤30℃. We first observed the four typical flow patterns, including bubble flow, bubble-churn flow, churn flow, annular flow, and the physical characteristics were studied and the corresponding differential pressure fluctuation signals measured for the four typical flow patterns. The dynamic characteristic of typical flow pattern was investigated by the of hierarchical entropy algorithm. Then the hierarchical entropy value of different flow patterns was calculated. The results indicate that the hierarchical entropy has a better ability to resist noise, and can reveal dynamics complexity of different flow pattern in rod bundle.
What influences the climate entrepreneurship? Chinese-based evidence
Authors: Li Cai , Asim Shoaib , Khalid Waleed , Sibt E. Ali Muhammad
Published: January 2023

Climate change is the biggest threat to the public as it threatens water scarcity, heat waves, economic losses, and food insecurity. Consequently, the control of climate entrepreneurship is very significant to ensure business sustainability. However, the identification of controlling measures for climate entrepreneurship remained unexplored. Therefore, the purpose of this study was to examine the influence of organizational performance, carbon management practices, and attitudes toward emission trading schemes on climate entrepreneurship. The study is based on 180 respondents from large Chinese firms. Using structural equation modeling, the results report a significantly negative influence of organizational performance, carbon management practices, and attitudes toward emission trading schemes on climate entrepreneurship. This suggests to the management and policymakers that an increase in organizational performance, carbon management practices, and attitude toward emission trading schemes brings a significant decline in climate entrepreneurship and, thus, ensures a sustained business environment. One of the few studies examines variations in company responses to climate change from an entrepreneurial viewpoint. In order to advance the body of knowledge on the strategic management of climate change challenges, the study offers a theoretical foundation. Chinese policymakers are very keen to adopt an emission trading scheme and by the implication of articulate results can help them to attain their climatic goals.
Decomposition of carbon emission influencing factors and research on emission reduction performance of energy consumption in China
Authors: Xiao Min , Peng Xingzhi
Published: January 2023

With the continuous progress of social production, it has brought huge benefits, but also led to an increasingly prominent global warming problem. Therefore, energy conservation and emission reduction has become an important direction of national industrial development. In order to promote the effective promotion of China’s carbon emission reduction action, the study adopted the improved STIRPAT model and Granger test to analyze the factors affecting China’s energy consumption carbon emissions, combined with Johan equation and GFI decomposition to decompose the factors affecting China’s energy consumption carbon emissions, excavated the key influencing conditions of China’s energy consumption carbon emissions, and put forward policy recommendations on energy consumption carbon emissions reduction. The results show that economic growth has the greatest impact on China’s per capita carbon emissions, followed by urbanization, industrial structure and energy structure. At the same time, industrial energy intensity has an inhibitory effect on per capita carbon emissions growth. From 2019 to 2021, Shanghai, Tianjin, Guangdong and other 10 provinces will achieve good emission reduction results. Therefore, in the analysis of energy conservation and emission reduction, it is of great value to understand the influencing factors of carbon emissions, which can provide direction and guidance for exploring an effective low-carbon development path, and play an important role in promoting the realization of the “double carbon” goal.
Respiratory Diseases' Burden in children and adolescents of marginalized population: A retrospective study in slum area of Karachi, Pakistan
Authors: Sharif Hina , Jan Shah Sumaya , Sharif Sana , Seemi Tooba , Naeem Hira , Rehman Junaid
Published: January 2023

Background

Worldwide, the burden of respiratory disease has dramatically increased, endangering public health. To our knowledge, there have been no reported cases of respiratory illness among children and adolescents living in the slums of Karachi, Pakistan. This study aimed to assess the burden of respiratory disease in marginalized slum populations and the factors causing such an increase in disease burden.

Methods

This study was conducted in 35 slums of Karachi, Pakistan, to determine the prevalence of respiratory disease in children and adolescents. Data on pneumonia, bronchitis, bronchiolitis, tuberculosis, and asthma from August 2019 to July 2022 were analyzed and inferences were drawn.

Results

Among the studied diseases, pneumonia was more prevalent among females (39,864, 44.9%), followed by males (19,006, 21.4%). Most of the children (59,988, 67.6%) were aged 1–5 years. In addition, of those diagnosed with pneumonia, 50,348 (56.8%) were from the same age group. Furthermore, bronchiolitis was found among 10,830 (12.2%) children aged 5–9 years. The majority (46,906, 52.9%) of the studied population belonged to the Pathan ethnicity, followed by Sindhi (21,522, 24.2%), and most of them (84,330, 95.1%) were of a lower socioeconomic status.

Conclusions

This study found that pneumonia is the most common respiratory disease followed by bronchiolitis in children and adolescents in a marginalized slum population of Karachi, Pakistan. Both pneumonia and bronchiolitis have seasonal variations in their occurrence.
Population genetic differentiation of Daphnia sinensis in a lasting high-phosphorus Chinese lake, Lake Chaohu
Authors: Zhang Kun , Wu Jianxun , Deng Daogui , Zhao Hui , Liu Qi , Peng Shuixiu , Zhang Yanan , Zhou Zhongze
Published: January 2023

Ecological shifts (e.g., eutrophication) can affect the genetic differentiation of zooplankton populations in lakes. However, the role of environmental change in a lasting high-phosphorus lake driving the genetic differentiation of zooplankton population structure over time is poorly understood. In this paper, the changes of the genetic diversity and differentiation ofDaphnia sinensispopulation were studied by using the mitochondrialCOI gene and microsatellite markers on modern groups (from January to June 2016) and historic groups (obtained from resting eggs in the sediments) in Lake Chaohu. Based on the microsatellite markers, six modern groups were clustered into two clusters (the WG cluster and SG cluster) during the seasonal dynamics, whereas the genetic differentiation of the five historic groups showed a wave-like pattern and had evolved into four clusters. Moreover, the haplotype network showed that six modern groups had one origin center whereas five historic groups had two origin centers based on the mitochondrialCOI gene marker. Fu’s Fs neutral test and Tajima’s test indicated that the five historic groups deviated from neutral evolution and showed a bottleneck effect in the history process. Water temperature and total dissolved phosphorus were obviously associated with the seasonal genetic differentiation ofD. sinensis, whereas nitrogen content of the sediments was significantly related to the long-term microevolution ofD. sinensisin the high-phosphorus environment. Therefore, the changing pattern ofD. sinensispopulation genetic structure was one of the environmental selections probably combined with co-evolutionary, where rapid-increasing nitrogen level had a large impact onD. sinensispopulation genetic structure in lasting high phosphorus environment in Lake Chaohu.
Insight into forensic efficiency and genetic structure of the Guizhou Dong group via a 64-plex panel
Authors: Wan Wen , Ren Zheng , Zhang Hongling , Wang Qiyan , Wang Ting , Yang Yunteng , You Jiangtao , He Kun , Huang Jiang , Jin Xiaoye
Published: January 2023

Insertion/deletion polymorphisms (InDels) show great application values in forensic research because they own superiorities of short tandem repeats (STRs) and single nucleotide polymorphisms (SNPs). Whereas, InDels commonly display low genetic diversities in comparison to STRs. Therefore, they may provide limited genetic information in forensic kinship testing. Here, we evaluated forensic application efficiency of a novel multiplex amplification system including two STRs, 59 InDels, and three sex-determination loci in the Guizhou Dong group. In addition, we explored the genetic background of the Guizhou Dong group in comparison to other reported populations based on 59 InDels. We found that 59 InDels displayed relatively high genetic diversities in the Guizhou Dong group. Moreover, the cumulative forensic efficiency of two STRs and 59 InDels could meet the requirement of individual identification and paternity testing in the Guizhou Dong group. For these 59 InDels, we observed that some loci exhibited relatively high genetic differentiations among different continental populations, especially for African and Non-African populations, which could be viewed as candidate ancestry informative markers in the future. Genetic structure results indicated that the Dong group had close genetic relationships with East Asian and some Southern Chinese Han populations. To sum up, we stated that the 64-plex panel could be performed for forensic application of the Guizhou Dong group.
Soil fertility and drought interact to determine large variations in wood production for a hyperdominant Amazonian tree species
Authors: Durgante Flavia Machado , Higuchi Niro , Ohashi Shinta , Householder John Ethan , Lima Adriano José Nogueira , Ishizuka Moriyoshi , Wittmann Florian , dos Santos Joaquim , Carneiro Vilany Matilla Colares , Xu Xiaomei , do Nascimento Claudete Catanhede , Schöngart Jochen , Piedade Maria Teresa Fernandez , Schmitt Adalberto Rodrigo Kossmann , Alves Yanka Laryssa Almeida , Lehman Jennifer , Gimenez Bruno Oliva , Baggio Priscilla Maia , de Ourique Lucas Kosvoski , Trumbore Susan
Published: January 2023

Introduction

The productivity of the Amazon Rainforest is related to climate and soil fertility. However, the degrees to which these interactions influence multiannual to decadal variations in tree diameter growth are still poorly explored.

Methods

To fill this gap, we used radiocarbon measurements to evaluate the variation in tree growth rates over the past decades in an important hyperdominant species, Eschweilera coriacea (Lecythidaceae), from six sites in the Brazilian Amazon that span a range of soil properties and climate.

Results

Using linear mixed-effects models, we show that temporal variations in mean annual diameter increment evaluated over a specific time period reflect interactions between soil fertility and the drought index (SPEI-Standardized Precipitation and Evapotranspiration Index).

Discussion

Our results indicate that the growth response of trees to drought is strongly dependent on soil conditions, a facet of forest productivity that is still underexplored, and which has great potential for improving predictions of future tropical tree growth in the face of projected climate change.
Light effects on seedling growth in simulated forest canopy gaps vary across species from different successional stages
Authors: Zhou Lingyan , Thakur Madhav P. , Jia Zhen , Hong Yu , Yang Wenjie , An Shuqing , Zhou Xuhui
Published: January 2023

Tropical forests continue to suffer from various kinds of disturbances in the Anthropocene. An immediate impact of disturbances on forest ecosystems is the creation of numerous large and small canopy gaps, which dramatically affect forest structure and function. Yet, we know little about the effect of canopy gaps on forest successional trajectory. More specifically, the responses of seedlings from different successional stages to increased light intensity under large and small canopy gaps in understory remain unclear. In this study, dominant tree seedlings from early-, mid-, and late-successional stages were selected, respectively from a tropical montane forest in Hainan Island, China to study their growth rate, biomass and traits. Our results showed that the light condition under small canopy gaps (SG, 10–15% of full sunlight) and large canopy gaps (LG, 40–50% of full sunlight) induced greater increment of relative growth rates for seedlings from early- and mid-successional stages relative to that in late-successional stage. Both SG and LG also significantly increased photosynthesis rate, leaf area (LA), light saturation point (LSP), root mass ratio (RMR) and root: shoot ratio, but decreased specific leaf area (SLA) of seedlings across successional stages. Tree seedlings from the early-successional stage displayed the greatest decrease in leaf mass ratio, increase in LA, LSP, and RMR, in comparison to those from mid- and late- successional stages. Light condition and SLA were the most important factors for seedlings’ relative growth rate across successional stages. SLA connected the interaction between the light condition and successional stage on seedlings’ growth, thereby jointly explaining the 93% variation of seedlings’ growth, combining with area-based light saturated rate of CO2 assimilation. Our study highlights the distinct effect of disturbance-induced canopy gaps on seedling regeneration in the understory in tropical forest due to the variation of light intensity. We suspect that the seedlings from late-successional stage will recover relatively slow after disturbances causing canopy losses, which can have detrimental impacts on structure feature and successional trajectory in tropical forest, as well as forest-based ecosystem services.
The gene signature of tertiary lymphoid structures within ovarian cancer predicts the prognosis and immunotherapy benefit
Authors: Hou Yue , Qiao Sijing , Li Miao , Han Xue , Wei Xuan , Pang Yingxin , Mao Hongluan
Published: January 2023

Ovarian cancer (OC) has the lowest survival rate among gynecologic malignancies. Ectopic lymphocyte aggregates, namely tertiary lymphoid structures (TLSs), have been reported as positive biomarkers for tumor prognosis. However, the related gene signature of tertiary lymphoid structure in ovarian cancer was less understood. Therefore, this study first exhibited the organizational patterns of tertiary lymphoid structure by H&E staining and immunohistochemistry (IHC), and confirmed the improved survival values of tertiary lymphoid structure and quantified tumor-infiltrating lymphocytes (CD20+ B cells and CD8+ T cells) in ovarian cancer patients. Secondly, we collected the genes involved in tertiary lymphoid structure from databases. By the univariate regression analysis, the tertiary lymphoid structure gene signature (CETP, CCR7, SELL, LAMP3, CCL19, CXCL9, CXCL10, CXCL11, and CXCL13) with prognostic value, characteristically of ovarian cancer, was constructed in the TCGA dataset and validated in the GSE140082 dataset. Thirdly, by performing CIBERSORT and Tumor Immune Dysfunction and Exclusion (TIDE) analysis, we found that the high expression of this gene signature was positively correlated with developed immune infiltration and reduced immune escape. The improved IPS score and application in the IMvigor210 dataset received PD-L1 proved the predictive value of immunotherapy for this gene signature. Furthermore, this signature showed a better correlation between tumor mutation burden and classical checkpoint genes. In conclusion, Tertiary lymphoid structure plays important role in tumor immunity and the gene signature can be evaluated as a biomarker for predicting prognosis and guiding immunotherapy in ovarian cancer.
Expression of miR-320 and miR-204 in myocardial infarction and correlation with prognosis and degree of heart failure
Authors: Yang Yuanyuan , Guo Qiongya , Lu Min , Huang Yansheng , Yang Yu , Gao Chuanyu
Published: January 2023

Myocardial infarction is a very dangerous cardiovascular disease with a high mortality rate under the modern developed medical technology. miRNA is a small molecule regulatory RNA discovered in recent years, which can play an important role in many cancers and other diseases. Medical data, machine learning and medical care strategies supporting the Internet of Things (IoMT) have certain applications in the treatment of myocardial infarction. However, the specific pathogenesis of myocardial infarction is still unclear. Therefore, this paper aimed to explore the expression of microRNA-320 and microRNA-204 in myocardial infarction and used the expression of microRNA-320 and microRNA-204 to predict the prognosis of patients with myocardial infarction. In order to discuss the expression of microRNA-320 and microRNA-204 in myocardial infarction in more detail. In this paper, 40 patients in the trial period were selected for clinical research, and 10 patients with normal cardiac function were selected in NHF group as control group. 10 patients with heart failure were selected as AMHF group. 10 patients with acute myocardial infarction were selected as AMNHF group. 10 patients with heart failure after old myocardial infarction were selected as OMHF group. AMHF group, AMNHF group and OMHF group were taken as the case group. This paper analyzed the difference of miR between different groups and determined that there were significant differences in the expression of miR-320 and miR-204 between different groups. Finally, the expression and prognosis of miR-320 and miR-204 in myocardial infarction were analyzed. The analysis results showed that the expression of microRNA-320 and microRNA-204 can inhibit the activity of myocardial cells. On the fifth day, the corresponding expression of microRNA-320 and microRNA-204 reduced the optical density of myocardial cells to 1.75 and 1.76, which was significantly lower than that on the first day. Moreover, excessive miR-320 expression and excessive miR-204 expression can increase the apoptosis rate of myocardial cells. The above results indicated that the high expression of microRNA-320 and microRNA-204 can be a bad prognostic factor in patients with myocardial infarction, showing that medical data, machine learning and medical care strategies supporting IoMT can play a role in the treatment of myocardial infarction. Therefore, it is urgent to understand the pathogenesis of heart failure after myocardial infarction and find new treatment schemes to improve the positive prognosis.
Trends in contraceptive method mix among adolescents and youth aged 15–24 in low- and middle-income countries
Authors: Bertrand Jane T. , Ross John A. , Sauter Sydney R.
Published: January 2023

Background

Method mix – the percent distribution of contraceptive use by method among contraceptive users – reflects both client choice of method and method availability. In a country where clients have access to a wide range of methods at an affordable price, method mix is a strong proxy for method choice. In contrast, where access is limited by numerous factors – method availability, cost, or provider attitudes – method mix may not capture method choice well. Given that method mix can be measured reliably from population-based surveys, it is useful in exploring method choice. While the method mix for all women of reproductive age (15–49 years) has been described previously, the method mix for adolescents and young women aged 15–24 remains unexplored despite this population's high risk for unintended pregnancy.

Objectives

This study investigates the contraceptive method mix for women aged 15–24 in low- and middle-income countries (LMICs) with national survey data and describes how the method mix differs by age group, geographic region, and marital status for women.

Methods

Using data from the Demographic and Health (DHS) Surveys, the contraceptive method mix among women aged 15–24 across 64 LMICs is analyzed by age, marital status, and region, with measures of skew and average deviation. Three case studies are presented in which the trend over time in the method mix is examined.

Results

There are large variations in method mixes across regions, which reflect their differences in various supply and demand constraints. However, there is consistently high usage of short-acting methods among both age groups, 15–19 and 20–24, compared to the full population of all women of reproductive age. Male condoms overwhelmingly predominate as the method used by women 15–24 in all regions.

Conclusion

The marked differences found by marital status, region, and age show the need for programs to be tailored to local circumstances. Additionally, the large unmet need for contraception signals the ongoing urgency for strengthened programmatic efforts, and for a wider offering of methods to enlarge the choices available to young women. Unmarried women in particular deserve attention, as well as young married women who wish to postpone a pregnancy.
Host blood-based biosignatures for subclinical TB and incipient TB: A prospective study of adult TB household contacts in Southern India
Authors: Sivakumaran Dhanasekaran , Jenum Synne , Srivastava Aashish , Steen Vidar M. , Vaz Mario , Doherty Timothy Mark , Ritz Christian , Grewal Harleen M. S.
Published: January 2023

A large proportion of the global tuberculosis (TB) burden is asymptomatic and not detectable by symptom-based screening, driving the TB epidemic through continued M. tuberculosis transmission. Currently, no validated tools exist to diagnose incipient and subclinical TB. Nested within a large prospective study in household contacts of pulmonary TB cases in Southern India, we assessed 35 incipient TB and 12 subclinical TB cases, along with corresponding household active TB cases (n=11), and household controls (n=39) using high throughput methods for transcriptional and protein profiling. We split the data into training and test sets and applied a support vector machine classifier followed by a Lasso regression model to identify signatures. The Lasso regression model identified an 11-gene signature (ABLIM2, C20orf197, CTC-543D15.3, CTD-2503O16.3, HLADRB3, METRNL, RAB11B-AS1, RP4-614C10.2, RNA5SP345, RSU1P1, and UACA) that distinguished subclinical TB from incipient TB with a very good discriminatory power by AUCs in both training and test sets. Further, we identified an 8-protein signature comprising b-FGF, IFNγ, IL1RA, IL7, IL12p70, IL13, PDGF-BB, and VEGF that differentiated subclinical TB from incipient TB with good and moderate discriminatory power by AUCs in the training and test sets, respectively. The identified 11-gene signature discriminated well between the distinct stages of the TB disease spectrum, with very good discriminatory power, suggesting it could be useful for predicting TB progression in household contacts. However, the high discriminatory power could partly be due to over-fitting, and validation in other studies is warranted to confirm the potential of the immune biosignatures for identifying subclinical TB.
Fecal microbiota transplantation and short-chain fatty acids reduce sepsis mortality by remodeling antibiotic-induced gut microbiota disturbances
Authors: Lou Xiran , Xue Jinfang , Shao Ruifei , Yang Yan , Ning Deyuan , Mo Chunyan , Wang Fuping , Chen Guobing
Published: January 2023

Objective

Sepsis is the leading cause of death in critically ill patients. The gastrointestinal tract has long been thought to play an important role in the pathophysiology of sepsis. Antibiotic therapy can reduce a patient’s commensal bacterial population and raise their risk of developing subsequent illnesses, where gut microbiota dysbiosis may be a key factor.

Methods

In this study, we analyzed the 16S rRNA of fecal samples from both healthy people and patients with sepsis to determine if alterations in gut bacteria are associated with sepsis. Then, we developed a mouse model of sepsis using cecal ligation and puncture (CLP) in order to examine the effects of fecal microbiota transplantation (FMT) and short-chain fatty acids (SCFAs) on survival rate, systemic inflammatory response, gut microbiota, and mucosal barrier function.

Results

Sepsis patients’ gut microbiota composition significantly differed from that of healthy people. At the phylum level, the amount of Proteobacteria in the intestinal flora of sepsis patients was much larger than that of the control group, whereas the number of Firmicutes was significantly lower. Mice with gut microbiota disorders (ANC group) were found to have an elevated risk of death, inflammation, and organ failure as compared to CLP mice. However, all of these could be reversed by FMT and SCFAs. FMT and SCFAs could regulate the abundance of bacteria such as Firmicutes, Proteobacteria, Escherichia Shigella, and Lactobacillus, restoring them to levels comparable to those of healthy mice. In addition, they increased the expression of the Occludin protein in the colon of mice with sepsis, downregulated the expression of the NLRP3 and GSDMD-N proteins, and reduced the release of the inflammatory factors IL-1β and IL-18 to inhibit cell pyroptosis, ultimately playing a protective role in sepsis.

Disccusion

FMT and SCFAs provide a microbe-related survival benefit in a mouse model of sepsis, suggesting that they may be a viable treatment for sepsis.
Immunotherapeutic approaches in EBV-associated nasopharyngeal carcinoma
Authors: Li Wenting , Duan Xiaobing , Chen Xingxing , Zhan Meixiao , Peng Haichuan , Meng Ya , Li Xiaobin , Li Xian-Yang , Pang Guofu , Dou Xiaohui
Published: January 2023

Epstein–Barr virus (EBV) was the first tumor virus in humans. Nasopharyngeal carcinoma (NPC) accounts for approximately 60% of the 200,000 new tumor cases caused by EBV infection worldwide each year. NPC has an insidious onset and is highly malignant, with more than 70% of patients having intermediate to advanced disease at the time of initial diagnosis, and is strongly implicated in epithelial cancers as well as malignant lymphoid and natural killer/T cell lymphomas. Over 90% of patients with confirmed undifferentiated NPC are infected with EBV. In recent decades, much progress has been made in understanding the molecular mechanisms of NPC and developing therapeutic approaches. Radiotherapy and chemotherapy are the main treatment options for NPC; however, they have a limited efficacy in patients with locally advanced or distant metastatic tumors. Tumor immunotherapy, including vaccination, adoptive cell therapy, and immune checkpoint blockade, represents a promising therapeutic approach for NPC. Significant breakthroughs have recently been made in the application of immunotherapy for patients with recurrent or metastatic NPC (RM-NPC), indicating a broad prospect for NPC immunotherapy. Here, we review important research findings regarding immunotherapy for NPC patients and provide insights for future research.
Temporal trends of COVID-19 antibodies in vaccinated healthcare workers undergoing repeated serological sampling: An individual-level analysis within 13 months in the ORCHESTRA cohort
Authors: Collatuzzo Giulia , De Palma Giuseppe , Violante Francesco S. , Porru Stefano , Larese Filon Francesca , Fabianova Eleonora , Violán Concepción , Vimercati Luigi , Leustean Mihaela , Rodriguez-Suarez Marta Maria , Sansone Emanuele , Sala Emma , Zunarelli Carlotta , Lodi Vittorio , Monaco Maria Grazia Lourdes , Spiteri Gianluca , Negro Corrado , Beresova Jana , Carrasco-Ribelles LucÌa A. , Tafuri Silvio , Asafo Shuffield S. , Ditano Giorgia , Abedini Mahsa , Boffetta Paolo
Published: January 2023

Short summary

We investigated changes in serologic measurements after COVID-19 vaccination in 19,422 subjects. An individual-level analysis was performed on standardized measurements. Age, infection, vaccine doses, time between doses and serologies, and vaccine type were associated with changes in serologic levels within 13 months.

Background

Persistence of vaccine immunization is key for COVID-19 prevention.

Methods

We investigated the difference between two serologic measurements of anti-COVID-19 S1 antibodies in an individual-level analysis on 19,422 vaccinated healthcare workers (HCW) from Italy, Spain, Romania, and Slovakia, tested within 13 months from first dose. Differences in serologic levels were divided by the standard error of the cohort-specific distribution, obtaining standardized measurements. We fitted multivariate linear regression models to identify predictors of difference between two measurements.

Results

We observed a progressively decreasing difference in serologic levels from <30 days to 210–240 days. Age was associated with an increased difference in serologic levels. There was a greater difference between the two serologic measurements in infected HCW than in HCW who had never been infected; before the first measurement, infected HCW had a relative risk (RR) of 0.81 for one standard deviation in the difference [95% confidence interval (CI) 0.78–0.85]. The RRs for a 30-day increase in time between first dose and first serology, and between the two serologies, were 1.08 (95% CI 1.07–1.10) and 1.04 (95% CI 1.03–1.05), respectively. The first measurement was a strong predictor of subsequent antibody decrease (RR 1.60; 95% CI 1.56–1.64). Compared with Comirnaty, Spikevax (RR 0.83, 95% CI 0.75–0.92) and mixed vaccines (RR 0.61, 95% CI 0.51–0.74) were smaller decrease in serological level (RR 0.46; 95% CI 0.40–0.54).

Conclusions

Age, COVID-19 infection, number of doses, time between first dose and first serology, time between serologies, and type of vaccine were associated with differences between the two serologic measurements within a 13-month period.
The role of histone methylase and demethylase in antitumor immunity: A new direction for immunotherapy
Authors: Zhang Yuanling , Chen Junhao , Liu Hang , Mi Rui , Huang Rui , Li Xian , Fan Fei , Xie Xueqing , Ding Jie
Published: January 2023

Epigenetic modifications may alter the proliferation and differentiation of normal cells, leading to malignant transformation. They can also affect normal stimulation, activation, and abnormal function of immune cells in the tissue microenvironment. Histone methylation, coordinated by histone methylase and histone demethylase to stabilize transcription levels in the promoter area, is one of the most common types of epigenetic alteration, which gained increasing interest. It can modify gene transcription through chromatin structure and affect cell fate, at the transcriptome or protein level. According to recent research, histone methylation modification can regulate tumor and immune cells affecting anti-tumor immune response. Consequently, it is critical to have a thorough grasp of the role of methylation function in cancer treatment. In this review, we discussed recent data on the mechanisms of histone methylation on factors associated with immune resistance of tumor cells and regulation of immune cell function.
Immunotherapy or targeted therapy as the first-line strategies for unresectable hepatocellular carcinoma: A network meta-analysis and cost-effectiveness analysis
Authors: Liu Kun , Zhu Youwen , Zhu Hong
Published: January 2023

Introduction

The existence of many phase III randomized controlled trials (RCTs) of first-line treatment for unresectable hepatocellular carcinoma (HCC) puzzle doctors and patients in choosing the most effective treatment strategies. We aimed to assess the efficacy, safety, and cost-effectiveness of immunotherapy or targeted therapy as the first-line strategy for unresectable HCC.

Methods

The included clinical trials were retrieved from PubMed, Embase, the Cochrane library, and Web of Science databases, in which immunotherapy or targeted therapy was regarded as the first-line treatment for unresectable HCC, published in English between January 1, 2010, and September 20, 2022. We conducted a network meta-analysis (NMA) and cost-effectiveness analysis (CEA) from the Chinese payer’s perspective. Overall survival (OS), progression-free survival (PFS), the ranks of different treatments using P-score, and adverse events (AEs) were evaluated by NMA. Total costs, life-years (LYs), quality-adjusted life-years (QALYs), and incremental cost-benefit ratio (ICER) were estimated from 15-year Markov models developed by CEA.

Results

We identified 2,825 records, including 11,796 patients, from 15 RCTs. The NMA revealed that sintilimab plus a bevacizumab biosimilar (HR, 0.57; 95% CI, 0.43 to 0.75; P = 0.96) and camrelizumab plus rivoceranib (HR, 0.56; 95% CI, 0.41 to 0.66; P = 0.94) could lead to great improvements in OS and PFS compared with sorafenib-related survival. The CEA indicated that tislelizumab increased by 0.220 QALYs (0.312 LYs) and decreased by $1,938 compared with sorafenib, which yielded ICERs of -$8,809/QALY (-$2,612/LY). Sensitivity analysis showed that the model was stable.

Conclusion

Sintilimab plus a bevacizumab biosimilar and camrelizumab plus rivoceranib significantly prolonged OS and PFS, respectively. Further considering the pharmacoeconomics factors, tislelizumab is the most cost-effective first-line treatment strategy for unresectable HCC in China.
The path to the construction of a domestic and international dual cycle of China’s shipping industry
Authors: Cao Xingguo , Zhang Xu , Chang Yen-Chiang
Published: January 2023

Being the adjustment of the development strategy of the People’s Republic of China (hereinafter referred to as the “PRC”), the new domestic and international dual-cycle development pattern forms the policy framework and target of the PRC’s future shipping industry. By exam the policy innovations taken in the Pilot Free Trade Zones/Free Trade Port and high-level Free Trade Agreements signed by PRC, this paper provides a conceptual research on the path to the construction of a domestic and international dual cycle of the PRC’s shipping industry. It is argued that the internal shipping policy innovations and international agreements has laid the foundation of the path, but resistance such as weak modern shipping service industry, unattractive international shipping system, and myriad of uncertain factors and challenges need to be addressed. It is deemed necessary to optimize the deployment of shipping industry in the logistic system and strengthen the innovation of new development model with combination of digital technologies.
Engineering vulnerability evaluation of building structures in coastal areas considering the effects of corrosion
Authors: Chi Xiaona , Xu Anna , Liu Yajie , Lun Peiyuan
Published: January 2023

Chloride-induced corrosion is an important factor that affects the durability of building structures in coastal areas; it causes serious deterioration of reinforced concrete (RC) structures and leads to structural failure. However, chloride-induced corrosion is a slow process which spans the whole service life of building structures, and many factors can affect their service life, such as location, structural design, and drug management. This paper aims to predict the service life of building structures in terms of chloride-induced corrosion and through the concept of engineering vulnerability. It first investigates the model of corrosion initiation of reinforcement, along with the consequent concrete cover cracking. Second, according to the characteristics of building structure and corrosion, it determines an evaluation index system of engineering vulnerability and establishes an evaluation method of engineering vulnerability, considering that corrosion is based on the AHP method and fuzzy comprehensive evaluation. Finally, using a case study of a pharmaceutical factory structure in a coastal city, this study verifies the feasibility of the assessment method considering corrosion effects.
An update of the effects of vitamins D and C in critical illness
Authors: Hill Aileen , Starchl Christina , Dresen Ellen , Stoppe Christian , Amrein Karin
Published: January 2023

Many critically ill patients are vitamin D and vitamin C deficient and the current international guidelines state that hypovitaminoses should be compensated. However, uncertainty about optimal dosage, timing and indication exists in clinical routine, mainly due to the conflicting evidence. This narrative review discusses both micronutrients with regards to pathophysiology, clinical evidence of benefits, potential risks, and guideline recommendations. Evidence generated from the most recent clinical trials are summarized and discussed. In addition, pragmatic tips for the application of these vitamins in the clinical routine are given. The supplementations of vitamin D and C represent cost-effective and simple interventions with excellent safety profiles. Regarding vitamin D, critically ill individuals require a loading dose to improve 25(OH)D levels within a few days, followed by a daily or weekly maintenance dose, usually higher doses than healthy individuals are needed. For vitamin C, dosages of 100–200 mg/d are recommended for patients receiving parenteral nutrition, but needs may be as high as 2–3 g/d in acutely ill patients.
Epidemiology and outcomes of hyponatremia in patients with COVID-19—A territory-wide study in Hong Kong
Authors: Chan Gordon Chun Kau , Wong Chun Ka , So Benjamin Y. F. , Ng Jack Kit Chung , Lui Grace Chung Yan , Szeto Cheuk Chun , Hung Ivan Fan Ngai , Tse Hung Fat , Tang Sydney C. W. , Chan Tak Mao , Chow Kai Ming , Yap Desmond Y. H.
Published: January 2023

Background

Hyponatremia is common in COVID-19, but its epidemiology and impact on clinical outcomes in relation to different variants, especially the Omicron variant, requires further clarification.

Methods

This was a territory-wide retrospective study to investigate the epidemiology and outcomes of COVID-19 patients with hyponatremia from January 1, 2020 to March 31, 2022 in Hong Kong. The primary outcome was 30-day mortality of patients with COVID-19 and hyponatremia at presentation. Secondary outcomes included rate of hospitalization, intensive care unit (ICU) hospitalization, overall duration of hospitalization, and duration of ICU hospitalization.

Results

A total of 53,415 COVID-19 patients were included for analysis, of which 14,545 (27.2%) had hyponatremia at presentation. 9813 (67.5%), 2821 (19.4%), and 1911 (13.1%) had mild (130 to <135 mmol/L), moderate (125 to <130 mmol/L), and severe hyponatremia (<125 mmol/L) at presentation respectively. Age, male sex, diabetes, active malignancy, white cell count, serum creatinine, hypoalbuminemia, C-reactive protein, and viral loads were independent predictors for hyponatremia in COVID-19 patients (P < 0.001, for all). Hyponatremic patients had increased 30-day mortality (9.7 vs. 5.7%, P < 0.001), prolonged hospitalization (11.9 ± 15.1 days vs. 11.5 ± 12.1 days, P < 0.001), and more ICU admissions (7.0% vs. 3.3%, P < 0.001). Patients diagnosed during the “fifth wave” Omicron BA.2 outbreak had 2.29-fold risk (95% CI 2.02–2.59, P < 0.001) of presenting with hyponatremia compared to other waves.

Conclusion

Hyponatremia is common among COVID-19 patients, and may serve as a prognostic indicator for unfavorable outcomes and increased healthcare utilization in the evolving COVID-19 outbreak.