bluuebunny/crossref_metadata_2025 huggingface dataset:
A Method for Directly Extracting the Jacobian Matrix of the Power Flow Equations of a Power System in Polar Coordinates
Authors: Lyu Zhongliang , Wei Hua , Wei Hongbo
Published: June 2022

This paper presents a method to directly extract the Jacobian matrix of a power system’s power flow (PF) equations in polar coordinates (termed as DEJMP method). This method is designed to reduce the computational complexity of the extraction process and improve the computational efficiency of the relevant PF algorithm. Direct extraction of the Jacobian matrix from the complex power equation in polar coordinates precludes an increase in both the number of procedural steps and the computational expense, which is a problem associated with the conventional PF (C-PF) algorithm due to its requirement that the derivatives of the active and reactive bus power equations be taken in separate steps. The DEJMP method avoids the trigonometric calculations used in the conventional method for computing the Jacobian matrix, resulting in a significant increase in computational efficiency. In addition, simulation results obtained for IEEE-300, S-1047, S-2383, and S-9241 bus systems validate the efficiency of the DEJMP-based PF algorithm. The DEJMP-based PF algorithm requires more than 20% less time to calculate the PF than the C-PF algorithm. This decrease in computing time is more pronounced for large systems.
Using the Multiple Linear Regression Method for CO2 Flooding Evaluation in the Daqing Oilfield
Authors: Wang Zhenhua , Hou Jirui , Hao Hongda , Wang Cheng , Wang Likun
Published: June 2022

CO2 flooding and burial efficiency can be improved by establishing a standard for screening suitable CO2 flooding reservoirs for the Daqing Oilfield. Moreover, the influencing factors of CO2 flooding can be classified into geological factors, fluid properties, and development factors. An evaluation index system and hierarchical structure are created based on the importance of multiple factors. The subjective analysis error of human beings is quite large when establishing the evaluation index system, especially in the fitting curves that are drawn by different analysts. Based on the geological characteristics of block Bei14 in the Daqing Oilfield, a typical CMG model is presented in this article. A total of 15 factors in the 72 models are used as independent variables, and the recovery factor is used as a dependent variable for multiple linear regression calculations. In addition to sensitivity tests based on how much significance is indicated by the t value in the results, a unique result can be calculated using standard statistical methods when analyzing the calculation results of the multiple linear regression model. The results of the screening standard evaluation system are consistent with the production history of the oilfield based on the mathematical understanding of multiple factors of CO2 flooding. Around the high-score well group, oil saturation decreases significantly, and the cumulative production is generally higher than that of the low-score well group. The calculation results of block Bei 14 show that 74% of well groups have an evaluation value greater than 0.50, and 72% of well groups have an annual oil exchange ratio above 40%, which means that over 70% of well groups can benefit from CO2 flooding. Thus, CO2 flooding can be applied in the Daqing Oilfield, and multiple linear regression can provide effective guidance for the Daqing Oilfield’s development.
Political Sensitivity and Carbon Emissions: Evidence From a Quasi-Natural Experiment of Leadership Change in China
Authors: Su Zhi , Liu Peng , Wu Liyan
Published: June 2022

While there is extensive literature assessing the impact of command-and-control and market-incentive environmental regulation on carbon emissions, it overlooks the fact that command-and-control environmental regulation and market-incentive environmental regulation are the embodiment of the national concept of green development. When a national leader with a green development philosophy is in power, local governments (due to the competition among them) adjust the economic development strategies and targets in their jurisdictions according to the leaders’ philosophy, resulting in differences in urban carbon emissions. Based on Chinese urban panel data from 2010 to 2016, this study uses a difference-in-differences approach to assess the impact of a national leader with a green development philosophy in power on carbon emissions in cities with different political sensitivities and the mechanisms of the impact. Our study finds that after the change in national leadership, the carbon intensity of high politically sensitive cities decreases significantly compared to low politically sensitive cities. We further find that increasing urban green areas and limiting the development of high-polluting industries are two ways to reduce carbon emission intensity in highly politically sensitive cities. A heterogeneity test demonstrates that the higher the level of economic development of the region where the city is located, the fewer the number of industrial enterprises in the city, the lower the total industrial output value of the city, and the more domestic enterprises in the city, proving that the change of national leaders more significantly impacts the city’s carbon emission. Our study suggests that policymakers should pay careful attention to the system of appraisal of officials, urban greening and development of highly polluting industries, and differentiated environmental policies.
Effects of Water Pollution on Human Health and Disease Heterogeneity: A Review
Authors: Lin Li , Yang Haoran , Xu Xiaocang
Published: June 2022

Background: More than 80% of sewage generated by human activities is discharged into rivers and oceans without any treatment, which results in environmental pollution and more than 50 diseases. 80% of diseases and 50% of child deaths worldwide are related to poor water quality.

Methods: This paper selected 85 relevant papers finally based on the keywords of water pollution, water quality, health, cancer, and so on.

Results: The impact of water pollution on human health is significant, although there may be regional, age, gender, and other differences in degree. The most common disease caused by water pollution is diarrhea, which is mainly transmitted by enteroviruses in the aquatic environment.

Discussion: Governments should strengthen water intervention management and carry out intervention measures to improve water quality and reduce water pollution’s impact on human health.
Quiet New Particle Formation in the Atmosphere
Authors: Kulmala Markku , Junninen Heikki , Dada Lubna , Salma Imre , Weidinger Tamás , Thén Wanda , Vörösmarty Máté , Komsaare Kaupo , Stolzenburg Dominik , Cai Runlong , Yan Chao , Li Xinyang , Deng Chenjuan , Jiang Jingkun , Petäjä Tuukka , Nieminen Tuomo , Kerminen Veli-Matti
Published: June 2022

Atmospheric new particle formation (NPF) has been observed to take place in practice all around the world. In continental locations, typically about 10–40% of the days are so-called NPF event days characterized by a clear particle formation and growth that continue for several hours, occurring mostly during daytime. The other days are either non-event days, or days for which it is difficult to decide whether NPF had occurred or not. Using measurement data from several locations (Hyytiälä, Järvselja, and near-city background and city center of Budapest), we were able to show that NPF tends to occur also on the days traditionally characterized as non-event days. One explanation is the instrument sensitivity towards low number concentrations in the sub-10 nm range, which usually limits our capability to detect such NPF events. We found that during such days, particle formation rates at 6 nm were about 2–20% of those observed during the traditional NPF event days. Growth rates of the newly formed particles were very similar between the traditional NPF event and non-event days. This previously overlooked phenomenon, termed as quiet NPF, contributes significantly to the production of secondary particles in the atmosphere.
Influence of Multi-Scale Meteorological Processes on PM2.5 Pollution in Wuhan, Central China
Authors: Miao Yucong , Zhang Xinxuan , Che Huizheng , Liu Shuhua
Published: June 2022

Heavy PM2.5 (particulate matter with an aerodynamics diameter less than 2.5 μm) pollution frequently happens in Wuhan under unfavorable meteorological conditions. To comprehensively understand the complex impact of both regional-scale synoptic forcing and local-scale processes within the planetary boundary layer (PBL) on air quality in Wuhan, this study analyzed long-term PM2.5 concentration measurement, near-surface and upper-air meteorological observations from March 2015 to February 2019, in combination with the Modern-Era Retrospective Analysis for Research and Applications version 2 (MERRA-2). We found that in winter the day-to-day change of PM2.5 pollution level in Wuhan was governed by the synoptic warm/cold advection, in addition to the high emissions of pollutants. The synoptic condition can largely determine both the vertical development of PBL and horizontal transport of pollutants. When a high-pressure system is located to the north of Wuhan at the 900-hPa level, the induced warm advection above 1,000 m can enhance the thermal stability of lower troposphere and inhibit the development of daytime PBL, leading to a decreased dispersion volume for pollutants. Meanwhile, within the PBL the pollutants emitted from Henan, Shandong, and Anhui provinces can be transported to Wuhan, further worsening the pollution. Our results highlight the importance of coordinated pollution controls in Central China and adjacent north regions under the unfavorable synoptic condition.
Effect of Financial Development, Foreign Direct Investment, Globalization, and Urbanization on Energy Consumption: Empirical Evidence From Belt and Road Initiative Partner Countries
Authors: Ullah Atta , Kui Zhao , Pinglu Chen , Sheraz Muhammad
Published: June 2022

This research aimed to determine the dynamic endogeneity nexus among energy consumption (EC), financial development (FD), foreign direct investment (FDI), globalization (GI), and urbanization (URBAN). The study used 64 countries’ annual panel data on “the Belt and Road Initiative (BRI)” from 2009 to 2019. Moreover, it employed a two-step system GMM, robust and results, that indicates financial development and urbanization are positively correlated with energy consumption, suggesting that these two factors raise the energy demand. Contrastingly, globalization negatively impacts energy demand, implying that global connectivity is essential for BRI countries. Foreign direct investment (FDI) has a positive but insignificant connection with energy consumption. Additionally, the Granger causality test was employed to explore the causal association among the variables, and outcomes reveal a bidirectional causal connection between FD and energy consumption. The study also suggests sustainable energy policy implications, which will be helpful to policymakers and governments for ensuring a balanced, sustainable growth.

JEL Code: P48; P25; Q4; F6; G00; E2
How Does Different Cropland Expansion Trajectories Affect Cropland Fragmentation? Insights From Three Urban Agglomerations in Yangtze River Economic Belt, China
Authors: Wang Liye , Zhang Siyu , Xie Yifan , Liu Yanfang , Liu Yaolin
Published: June 2022

A clear understanding of cropland expansion dynamics and their effects is vital for cropland protection and food security. However, the trajectories of cropland expansion have been less discussed. This study referred to the modes of landscape expansion and assessed the cropland expansion trajectory in three urban agglomerations in the Yangtze River Economic Belt and its impact on cropland fragmentation. Specifically, we identified three cropland expansion trajectories using the landscape expansion index, namely, infilling, edge-expansion, and outlying. Moreover, the surface relief amplitude model was employed to characterize the relief amplitude effect on cropland expansion trajectories. By coupling landscape metrics (e.g., patch density, landscape shape index, the largest patch index, and aggregation index) and Spearman correlation analysis, the relationship between cropland expansion trajectories and cropland fragmentation was assessed. Results show that (1) three urban agglomerations experience cropland expansion, in which the edge-expansion trajectory is primary, followed by infilling and outlying trajectories; (2) the cumulative frequency curve indicates that infilling and edge-expansion trajectories are likely to be distributed in low topographic relief amplitude regions, while the outlying trajectory is located in relatively higher topographic relief amplitude regions; and (3) infilling and edge-expansion trajectories contribute to a significantly positive relationship with the decrease of cropland fragmentation, while the outlying trajectory has a negative relationship with cropland fragmentation. This research highlights that cropland protection policies should considerably focus on the trajectory of cropland expansion, not only request the total area of cropland in a dynamic balance.
An Autophagy-Related Gene Signature can Better Predict Prognosis and Resistance in Diffuse Large B-Cell Lymphoma
Authors: Zhou Xuan , He Ying-Zhi , Liu Dan , Lin Chao-Ran , Liang Dan , Huang Rui , Wang Liang
Published: June 2022

Background: Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous disease, and about 30%–40% of patients will develop relapsed/refractory DLBCL. In this study, we aimed to develop a gene signature to predict survival outcomes of DLBCL patients based on the autophagy-related genes (ARGs).

Methods: We sequentially used the univariate, least absolute shrinkage and selector operation (LASSO), and multivariate Cox regression analyses to build a gene signature. The Kaplan–Meier curve and the area under the receiver operating characteristic curve (AUC) were performed to estimate the prognostic capability of the gene signature. GSEA analysis, ESTIMATE and ssGSEA algorithms, and one-class logistic regression were performed to analyze differences in pathways, immune response, and tumor stemness between the high- and low-risk groups.

Results: Both in the training cohort and validation cohorts, high-risk patients had inferior overall survival compared with low-risk patients. The nomogram consisted of the autophagy-related gene signature, and clinical factors had better discrimination of survival outcomes, and it also had a favorable consistency between the predicted and actual survival. GSEA analysis found that patients in the high-risk group were associated with the activation of doxorubicin resistance, NF-κB, cell cycle, and DNA replication pathways. The results of ESTIMATE, ssGSEA, and mRNAsi showed that the high-risk group exhibited lower immune cell infiltration and immune activation responses and had higher similarity to cancer stem cells.

Conclusion: We proposed a novel and reliable autophagy-related gene signature that was capable of predicting the survival and resistance of patients with DLBCL and could guide individualized treatment in future.
Histone Demethylase AMX-1 Regulates Fertility in a p53/CEP-1 Dependent Manner
Authors: Ren Xiaojing , Tian Sisi , Meng Qinghao , Kim Hyun-Min
Published: June 2022

Histone methylation shapes the epigenetic configuration and adjusts multiple fundamental nuclear processes, including transcription, cell cycle control and DNA repair. The absence of histone demethylase LSD1/SPR-5 leads to progressive fertility defects as well as a reduction in brood size. Similarly, C. elegans LSD2 homolog AMX-1 has been implicated in regulating H3K4me2 and maintaining interstrand crosslinks (ICL) susceptibility. However, the mechanisms of how lack of AMX-1 induces sterility have not been addressed so far. This study investigated the histone demethylase AMX-1 in C. elegans and uncovered how amx-1 contributes to sterility in a p53/CEP-1 dependent manner. We show that while sterility in spr-5 mutants exhibited progressive over generations, amx-1 mutants displayed non-transgenerational fertility defects. Also, amx-1 mutants exhibited a reduced number of sperms and produced low brood size (LBS) or sterile worms that retain neither sperms nor germline nuclei, suggesting that fertility defects originated from germline development failure. Surprisingly, sterility exhibited in amx-1 was mediated by p53/CEP-1 function. Consistent with this result, upregulation of Piwi expression in amx-1 mutants suggested that AMX-1 is essential for germline development by regulating Piwi gene expressions. We propose that AMX-1 is required for proper Piwi expression and transposon silencing in a p53/CEP-1 dependent manner; thus, the absence of AMX-1 expression leads to defective meiotic development and sterility. This study elucidates how LSD2/AMX-1 contributes to sterility, therefore, expanding the boundaries of histone demethylase function.
Identifying Autophagy-Related lncRNAs and Potential ceRNA Networks in NAFLD
Authors: Cao Ziyi , Guan Li , Yu RunZhi , Chen Jie
Published: June 2022

Nonalcoholic fatty liver disease (NAFLD) is a common chronic disease with complex pathogenesis, which brings economic burden to the society, and there is still no effective therapy. Impaired autophagy has been implicated in the development of NAFLD. Long noncoding RNAs (lncRNAs) are also reported to play a role in the pathogenesis of NAFLD. However, the role of autophagy-related lncRNAs in NAFLD disease has not been elucidated. Here, we mined GSE135251, GSE160016, GSE130970 and GSE185062 datasets from the Gene Expression Omnibus database (GEO) and obtained the human autophagy-related gene list from the Human Autophagy Database (HADb) for in-depth bioinformatic analysis. Following differential expression analysis and intersection of the datasets, Pearson correlation analysis was performed on DElncRNAs and autophagy-related DEmRNAs to obtain autophagy-related lncRNAs, and then Starbase3.0 and TargetScan7.2 were used to construct competing endogenous RNAs (ceRNA) regulatory networks. We constructed four lncRNA-dominated ceRNA regulatory networks (PSMG3-AS1, MIRLET7BHG, RP11-136K7.2, LINC00925), and visualized with Cytoscape. Then we performed co-expression analysis of the ceRNA networks and autophagy-related genes, and functionally annotated them with Metascape. Finally, we performed receiver operating characteristic curve (ROC) analysis on lncRNAs and mRNAs within the ceRNA networks. Conclusively, our project is the first to study autophagy-related lncRNAs in NAFLD and finally mined four autophagy-related lncRNAs (PSMG3-AS1, MIRLET7BHG, RP11-136K7.2, LINC00925). We suggested that the four autophagy-related lncRNAs may be closely associated with the occurrence and development of NAFLD through the corresponding ceRNA regulatory networks. This research brings new horizons to the study of NAFLD.
Isolation, Identification, and Investigation of Pathogenic Bacteria From Common Carp (Cyprinus carpio) Naturally Infected With Plesiomonas shigelloides
Authors: Chen Huijie , Zhao Yuanli , Chen Kuangxin , Wei Yulai , Luo Hongrui , Li Yongming , Liu Fei , Zhu Zuoyan , Hu Wei , Luo Daji
Published: June 2022

Various bacterial diseases have caused great economic losses to the high-density and intensive aquaculture industry; however, the pathogenic mechanism underlying the large-scale challenged to caused by many bacteria remain unclear, making the prevention and treatment of these diseases difficult. In the present study, we isolated a bacterial strain from Cyprinus carpio having a typical bacterial disease and named it Cc2021. Through subsequent morphological observations, a regression challenge, biochemical identification, and 16S rRNA gene sequence analysis, we determined Cc2021 to be Plesiomonas shigelloides. Subsequently, we comprehensively investigated the pathogenicity of P. shigelloides in C. carpio through a regression challenge and assessed the underlying the pathogenic mechanism. Mortality results revealed that P. shigelloides is highly pathogenic and infects various tissues throughout the body, resulting in edema of the liver, spleen, and body and head kidneys. Histopathological analysis revealed obvious inflammation, bleeding, and necrosis in the intestine, spleen, and head kidney. The body’s immune tissues actively produce complement C3, superoxide dismutase, and lysozyme after a challenge to resist bacterial invasion. With regard to the underlying pathogenesis of P. shigelloides, comparative transcriptome analysis revealed 876 upregulated genes and 828 downregulated genes in the intestine of C. carpio after the challenge. Analysis of differentially expressed unigenes revealed the involvement of major immune pathways, particularly the TNF signaling pathway, interleukin (IL)-17 signaling pathway, and Toll-like receptor signaling pathway. The present study provides new valuable information on the immune system and defense mechanisms of P. shigelloides.
Role of IgM Memory B Cells and Spleen Function in COVID-19
Authors: Rossi Carlo Maria , Lenti Marco Vincenzo , Merli Stefania , Di Sabatino Antonio
Published: June 2022

IgM memory B cells, are a peculiar subset of memory B cells, which probably originates in the spleen and outside germinal centers and provide a rapid line of defence against mucosal infections. Their role in counteracting COVID-19 is still elusive but, recent evidence, mainly boosted by studies on spleen function/involvement in COVID-19, seems to support the notion that this subset of memory B cells could exert a protective role against this virus, along with other coronaviruses, particularly in the acute setting of the infection, as outlined by worst clinical outcomes observed in unvaccinated patients with impaired IgM B memory response and spleen function. Herein we critically summarise the current landscape of studies on IgM memory B cells, focusing on the clinical impact of their depletion, by comparing the COVID-19-related splenic dysfunction with other hypo- and asplenic conditions and by adding recent data on follow-up studies and postulate a mechanistic explanation for their reduced numbers. The early detection of an impaired IgM memory B cell response in patients with COVID-19 may contribute to their improved care through different strategies, such as through tailored vaccine strategies, prompt hospital admission and/or administration of anti-infective treatments, thus resulting in an better prognosis, although at present management algorithms are still unavailable. Moreover, further studies with longer follow-up are needed to assess the evolution of COVID-19-associated/exacerbated immune deficit.
Senescent Tumor Cells in the Peritoneal Carcinomatosis Drive Immunosenescence in the Tumor Microenvironment
Authors: Braumüller Heidi , Mauerer Bernhard , Berlin Christopher , Plundrich Dorothea , Marbach Patrick , Cauchy Pierre , Laessle Claudia , Biesel Esther , Holzner Philipp Anton , Kesselring Rebecca
Published: June 2022

More than half of all patients with colorectal cancer (CRC) develop distant metastasis and, depending on the local stage of the primary tumor, up to 48% of patients present peritoneal carcinomatosis (PC). PC is often considered as a widespread metastatic disease, which is almost resistant to current systemic therapies like chemotherapeutic and immunotherapeutic regimens. Here we could show that tumor cells of PC besides being senescent also exhibit stem cell features. To investigate these surprising findings in more detail, we established a murine model based on tumor organoids that resembles the clinical setting. In this murine orthotopic transplantation model for peritoneal carcinomatosis, we could show that the metastatic site in the peritoneum is responsible for senescence and stemness induction in tumor cells and that induction of senescence is not due to oncogene activation or therapy. In both mouse and human PC, senescence is associated with a senescence-associated secretory phenotype (SASP) influencing the tumor microenvironment (TME) of PC. SASP factors are able to induce a senescence phenotype in neighbouring cells. Here we could show that SASP leads to enhanced immunosenescence in the TME of PC. Our results provide a new immunoescape mechanism in PC explaining the resistance of PC to known chemo- and immunotherapeutic approaches. Therefore, senolytic approaches may represent a novel roadmap to target this terminal stage of CRC.
Rituximab Therapy for Mucous Membrane Pemphigoid: A Retrospective Monocentric Study With Long-Term Follow-Up in 109 Patients
Authors: Bohelay Gérôme , Alexandre Marina , Le Roux-Villet Christelle , Sitbon Ishaï , Doan Serge , Soued Isaac , Shourick Jason , Rousset Laurie , Mellottee Benoît , Heller Michel , Lièvre Nicole , Zumelzu Coralie , Morin Florence , Grootenboer-Mignot Sabine , Gabison Eric , Caux Frédéric , Prost-Squarcioni Catherine , Musette Philippe
Published: June 2022

Mucous membrane pemphigoid (MMP) is a heterogeneous group of rare, chronic, subepithelial autoimmune blistering diseases (AIBDs) with predominant involvement of mucous membranes that can be sight-threatening and life-threatening. Rituximab (RTX) has demonstrated its efficacy in severe MMP refractory to conventional immunosuppressants in small series that differed in RTX scheme, concomitant therapies, and outcome definitions. In a meta-analysis involving 112 patients with MMP treated with RTX, complete remission (CR) was reported in 70.5% of cases. Herein, we report the largest retrospective monocentric study on RTX efficacy in a series of 109 severe and/or refractory patients with MMP treated with RTX with a median follow-up period of 51.4 months. RTX was administered in association with immunomodulatory drugs (dapsone, salazopyrine) without any other systemic immunosuppressant in 104 patients. The RTX schedule comprised two injections (1 g, 2 weeks apart), repeated every 6 months until CR or failure, with a unique consolidation injection (1 g) after CR. The median survival times to disease control and to CR were 7.1 months and 12.2 months, respectively. The median number of RTX cycles required to achieve CR in 85.3% of patients was two. The larynx was the lesional site that took the longest time to achieve disease control. One year after RTX weaning, CR off RTX was obtained in 68.7% of cases. CR off RTX with only minimum doses of immunomodulatory drugs was achieved in 22.0% of patients. Further, 10.1% of patients were partial responders and 4.6% were non-responders to RTX. Relapse occurred in 38.7% of cases, of whom 91.7% had achieved CR again at the last follow-up. In MMP, CR was achieved in a longer time and after more rituximab cycles than in pemphigus, especially for patients with MMP with anti-type VII collagen reactivity. RTX with concomitant immunomodulatory drugs was not responsible for an unusual proportion of adverse events. This large study confirms that RTX is an effective therapy in patients with severe and/or refractory MMP, corroborating previous findings regarding the effects of RTX on AIBDs such as pemphigus.
Determining the Optimal (Neo)Adjuvant Regimen for Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Regarding Survival Outcome: A Network Meta-Analysis
Authors: Cai Yu-Wen , Shao Zhi-Ming , Yu Ke-Da
Published: June 2022

Background

The optimal (neo)adjuvant regimen for human epidermal growth factor receptor-2 (HER2)-positive breast cancer regarding survival outcomes remains unclear.

Methods

We searched Web of Science, PubMed, and the Cochrane Central Register of Controlled Trials systematically to find out randomized controlled studies, up to January 2022, that compared different anti-HER2 regimens in the (neo)adjuvant setting. The primary endpoint was disease-free survival (DFS). We used a Bayesian statistical model to combine direct and indirect comparisons and used odds ratios (ORs) to pool effect sizes and performed the surface under the cumulative ranking area (SUCRA) curves to estimate the ranking probabilities of various regimens. For survival outcomes, we performed two parallel analyses, one based on data from both neoadjuvant and adjuvant studies and the other specific to adjuvant studies. All statistics were two-sided.

Results

Fifteen studies were finally enrolled. Regarding DFS, the overall analysis indicated that the top two regimens for HER2-positive breast cancer were chemotherapy plus trastuzumab with lapatinib, and chemotherapy plus trastuzumab with pertuzumab (SUCAR of 81% and 79%, respectively), with the OR of 0.99 [95% confidence interval (CI), 0.59 to 1.54]; the parallel analysis specific to adjuvant trials indicated that the top two regimens were chemotherapy plus trastuzumab with sequential neratinib, and chemotherapy plus trastuzumab with pertuzumab (SUCRA of 80% and 76%, respectively), with the OR of 1.04 (95% CI, 0.63 to 1.73). The dual-target therapy that combines trastuzumab and pertuzumab showed the highest risk of inducing cardiac events, with an SUCRA of 92%.

Conclusions

Chemotherapy plus trastuzumab and pertuzumab might be the optimal regimen for HER2-positive breast cancer in improving the survival rate. However, the cardiotoxicity of this dual-target therapy should be taken care of.
Immunolipidomics Reveals a Globoside Network During the Resolution of Pro-Inflammatory Response in Human Macrophages
Authors: Muralidharan Sneha , Torta Federico , Lin Michelle K. , Olona Antoni , Bagnati Marta , Moreno-Moral Aida , Ko Jeong-Hun , Ji Shanshan , Burla Bo , Wenk Markus R. , Rodrigues Hosana G. , Petretto Enrico , Behmoaras Jacques
Published: June 2022

Toll-like receptor 4 (TLR4)-mediated changes in macrophages reshape intracellular lipid pools to coordinate an effective innate immune response. Although this has been previously well-studied in different model systems, it remains incompletely understood in primary human macrophages. Here we report time-dependent lipidomic and transcriptomic responses to lipopolysaccharide (LPS) in primary human macrophages from healthy donors. We grouped the variation of ~200 individual lipid species measured by LC-MS/MS into eight temporal clusters. Among all other lipids, glycosphingolipids (glycoSP) and cholesteryl esters (CE) showed a sharp increase during the resolution phase (between 8h or 16h post LPS). GlycoSP, belonging to the globoside family (Gb3 and Gb4), showed the greatest inter-individual variability among all lipids quantified. Integrative network analysis between GlycoSP/CE levels and genome-wide transcripts, identified Gb4 d18:1/16:0 and CE 20:4 association with subnetworks enriched for T cell receptor signaling (PDCD1, CD86, PTPRC, CD247, IFNG) and DC-SIGN signaling (RAF1, CD209), respectively. Our findings reveal Gb3 and Gb4 globosides as sphingolipids associated with the resolution phase of inflammatory response in human macrophages.
Key Factors for Thymic Function and Development
Authors: Shichkin Valentin P. , Antica Mariastefania
Published: June 2022

The thymus is the organ responsible for T cell development and the formation of the adaptive immunity function. Its multicellular environment consists mainly of the different stromal cells and maturing T lymphocytes. Thymus-specific progenitors of epithelial, mesenchymal, and lymphoid cells with stem cell properties represent only minor populations. The thymic stromal structure predominantly determines the function of the thymus. The stromal components, mostly epithelial and mesenchymal cells, form this specialized area. They support the consistent developmental program of functionally distinct conventional T cell subpopulations. These include the MHC restricted single positive CD4+CD8-and CD4-CD8+cells, regulatory T lymphocytes (Foxp3+), innate natural killer T cells (iNKT), and γδT cells. Several physiological causes comprising stress and aging and medical treatments such as thymectomy and chemo/radiotherapy can harm the thymus function. The present review summarizes our knowledge of the development and function of the thymus with a focus on thymic epithelial cells as well as other stromal components and the signaling and transcriptional pathways underlying the thymic cell interaction. These critical thymus components are significant for T cell differentiation and restoring the thymic function after damage to reach the therapeutic benefits.
Acinetobacter baumannii Outer Membrane Protein A Induces Pulmonary Epithelial Barrier Dysfunction and Bacterial Translocation Through The TLR2/IQGAP1 Axis
Authors: Zhang Wang , Zhou Hua , Jiang Yan , He Jintao , Yao Yue , Wang Jianfeng , Liu Xiaochen , Leptihn Sebastian , Hua Xiaoting , Yu Yunsong
Published: June 2022

Pulmonary epithelial barrier dysfunction is a critical pathophysiological process in pneumonia and associated invasive infections, such as those caused by Acinetobacter baumannii. However, the mechanisms underlying A. baumannii-induced pulmonary epithelial barrier dysfunction and bacterial translocation remain unclear. In this study, lungs of mice and A549 human epithelial cell monolayers were challenged with the A. baumannii wild-type strain and an outer membrane protein A (ompA) deletion strain. In addition, epithelial cells in culture were treated with purified OmpA protein or transfected with a eukaryotic expression vector encoding ompA (pCMV-ompA). Bacterial translocation across cell monolayers and intrapulmonary burden were measured, barrier function was evaluated in vivo and in vitro; cell migration ability was determined. The specific inhibitors C29 and JSH-23 were used to suppress the activity of Toll-like receptor 2 (TLR2) and of NF-κB, respectively. IQ-GTPase-activating protein 1 (IQGAP1) small interfering RNA was used to knock down endogenous IQGAP1 expression. In this work, we show that OmpA from A. baumannii increased the production of pro-inflammatory cytokines, remodeled the cytoskeleton, and internalized intercellular adherens junctions (AJs); these changes eventually induced pulmonary epithelial barrier dysfunction to promote bacterial translocation. IQGAP1-targeting small interfering RNA and chemical inhibition of TLR2 or NF-κB prevented high permeability of the pulmonary epithelial barrier. TLR2/NF-κB signaling was involved in OmpA-induced inflammation, IQGAP1-mediated OmpA-induced opening of the pulmonary epithelial barrier via cytoskeleton dynamic remodeling, and cellular redistribution of the major AJ protein, E-cadherin. These observations indicate that A. baumannii uses OmpA to overcome epithelial defences and cross the pulmonary epithelial barrier.
Obesity-Mediated Immune Modulation: One Step Forward, (Th)2 Steps Back
Authors: Schmidt Viviane , Hogan Andrew E. , Fallon Padraic G. , Schwartz Christian
Published: June 2022

Over the past decades, the relationship between the immune system and metabolism has become a major research focus. In this arena of immunometabolism the capacity of adipose tissue to secrete immunomodulatory molecules, including adipokines, within the underlying low-grade inflammation during obesity brought attention to the impact obesity has on the immune system. Adipokines, such as leptin and adiponectin, influence T cell differentiation into different T helper subsets and their activation during immune responses. Furthermore, within the cellular milieu of adipose tissue nutrient availability regulates differentiation and activation of T cells and changes in cellular metabolic pathways. Upon activation, T cells shift from oxidative phosphorylation to oxidative glycolysis, while the differential signaling of the kinase mammalian target of rapamycin (mTOR) and the nuclear receptor PPARγ, amongst others, drive the subsequent T cell differentiation. While the mechanisms leading to a shift from the typical type 2-dominated milieu in lean people to a Th1-biased pro-inflammatory environment during obesity are the subject of extensive research, insights on its impact on peripheral Th2-dominated immune responses become more evident. In this review, we will summarize recent findings of how Th2 cells are metabolically regulated during obesity and malnutrition, and how these states affect local and systemic Th2-biased immune responses.
Effect of Platycodon grandiflorus Polysaccharide on M1 Polarization Induced by Autophagy Degradation of SOCS1/2 Proteins in 3D4/21 Cells
Authors: Li Liping , Chen Xufang , Lv Meiyun , Cheng Ziqiang , Liu Fang , Wang Ying , Zhou Aiqin , Liu Jianzhu , Zhao Xiaona
Published: June 2022

M1-polarized macrophages can improve the body’s immune function. This study aimed to explore the mechanism of Platycodon grandiflorus polysaccharide (PGPSt) degrading SOCS1/2 protein through autophagy and promoting M1 polarization in 3D4/21 cells. Immunoprecipitation, confocal laser scanning microscopy, flow cytometry, and intracellular co-localization were used to detect the expression of related phenotypic proteins and cytokines in M1-polarized cells. The results showed that PGPSt significantly promoted the mRNA expression of IL-6, IL-12, and TNF-α and enhanced the protein expression of IL-6, IL-12, TNF-α, IL-1β, iNOS, CD80, and CD86, indicating that PGPSt promoted M1 polarization in 3D4/21 cells. Next, the effect of the PGPSt autophagy degradation of SOCS1/2 on the M1 polarization of 3D4/21 cells was detected. The results showed that PGPSt significantly downregulated the expression level of SOCS1/2 protein, but had no obvious effect on the mRNA expression level of SOCS1/2, indicating that PGPSt degraded SOCS1/2 protein by activating the lysosome system. Further research found that under the action of 3-MA and BafA1, PGPSt upregulated LC3B II and downregulated SOCS1/2 protein expression, which increased the possibility of LC3B, the key component of autophagy, bridging this connection and degrading SOCS1/2. The interaction between SOCS1/2 and LC3 was identified by indirect immunofluorescence and Co-IP. The results showed that the co-localization percentage of the two proteins increased significantly after PGPSt treatment, and LC3 interacted with SOCS1 and SOCS2. This provides a theoretical basis for the application of PGPSt in the treatment or improvement of diseases related to macrophage polarization by regulating the autophagy level.
Defining the Realized Niche of the Two Major Clades of Trichodesmium: A Study on the West Florida Shelf
Authors: Confesor Kristina A. , Selden Corday R. , Powell Kimberly E. , Donahue Laura A. , Mellett Travis , Caprara Salvatore , Knapp Angela N. , Buck Kristen N. , Chappell P. Dreux
Published: June 2022

The cyanobacterium Trichodesmium plays an essential role supporting ocean productivity by relieving nitrogen limitation via dinitrogen (N2) fixation. The two common Trichodesmium clades, T. erythraeum and T. thiebautii, are both observed in waters along the West Florida Shelf (WFS). We hypothesized that these taxa occupy distinct realized niches, where T. thiebautii is the more oceanic clade. Samples for DNA and water chemistry analyses were collected on three separate WFS expeditions (2015, 2018, and 2019) spanning multiple seasons; abundances of the single copy housekeeping gene rnpB from both clades were enumerated via quantitative PCR. We conducted a suite of statistical analyses to assess Trichodesmium clade abundances in the context of the physicochemical data. We observed a consistent coastal vs. open ocean separation of the two clades: T. erythraeum was found in shallow waters where the concentrations of dissolved iron (dFe) and the groundwater tracer Ba were significantly higher, while T. thiebautii abundance was positively correlated with water column depth. The Loop Current intrusion in 2015 with entrained Missisippi River water brought higher dFe and elevated abundance of both clades offshore of the 50 m isobath, suggesting that both clades are subject to Fe limitation on the outer shelf. Whereas, previous work has observed that T. thiebautii is more abundant than T. erythraeum in open ocean surface waters, this is the first study to examine Trichodesmium niche differentiation in a coastal environment. Understanding the environmental niches of these two key taxa bears important implications for their contributions to global nitrogen and carbon cycling and their response to global climate change.
Design of an Optimal Testbed for Acoustic Tags: Test Case for Marine Megafauna
Authors: Alexandri Talmon , Diamant Roee
Published: June 2022

Underwater acoustic technologies are a key component for exploring the behavior of marine fauna such as sea turtles, sharks, and seals. The animals are marked with acoustic devices (tags) that periodically emit signals encoding the device’s ID along with sensor data such as depth, temperature, or the dominant acceleration axis - data that is collected by a network of deployed receivers. In this work, we aim to optimize the locations of receivers for best tracking of acoustically tagged marine fauna, and provide a test case with tags suitable for megafauna tracking. The outcomes of such tracking allows the evaluation of the animals’ motion patterns, their hours of activity, and their social interactions. In particular, we focus on how to determine the receivers’ deployment positions to maximize the coverage area in which the tagged animals can be tracked. For example, an overly-condensed deployment may not allow accurate tracking, whereas a sparse one, may lead to a small coverage area due to too few detections. We formalize the question of where to best deploy the receivers as a non-convex constraint optimization problem that takes into account the local environment and the specifications of the tags, and offer a sub-optimal, low-complexity solution that can be applied to large testbeds. Numerical investigation for three stimulated sea environments shows that our proposed method is able to increase the localization coverage area by 30%, and results from a test case experiment demonstrate similar performance in a real sea environment. We share the implementation of our work to help researchers set up their own acoustic observatory.
Sea Urchins in Acute High Temperature and Low Oxygen Environments: The Regulatory Role of microRNAs in Response to Environmental Stress
Authors: Han Lingshu , Wu Yanglei , Hao Pengfei , Ding Beichen , Li Yuanxin , Wang Wenpei , Zhang Xianglei , Gao Chuang , Wang Heng , Wang Luo , Zhang Weijie , Chang Yaqing , Ding Dewen , Ding Jun
Published: June 2022

Strongylocentrotus intermedius is an economically valuable sea urchin species in China. However, its growth and survival are severely constrained by ocean warming and the hypoxia that often accompanies high water temperatures. MicroRNAs (miRNAs) are important regulators of gene expression in response to environmental change. In this study, high-throughput RNA sequencing was used to investigate changes in miRNA expression in S. intermedius under heat (25°C), hypoxia (2 mg/L O2), and combined heat and hypoxia stresses. Twelve small RNAs libraries were constructed and 17, 14, and 23 differentially expressed miRNAs (DEMs) were identified in the heat, hypoxia, and combined stress groups (P<0.05), respectively. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway functional analyses of putative target genes of the DEMs suggested that these miRNAs were important in basal metabolism, apoptosis, oxidative stress, and immune-related pathways. By co-analysis with published transcriptome data, key DEMs (miR-193, miR-184, miR-133, miR-125, miR-2008) and their key target genes (EGF3, ABCB4, CYCL, PAN2, CALN) were identified. Quantitative real-time PCR analysis of the expression of 10 DEMs and their key target genes confirmed the RNA sequencing results. These results provide information on gene expression regulation of the molecular mechanisms underlying the response of S. intermedius to multi-cause environmental stresses.
Deep Learning Models for Segmenting Non-perfusion Area of Color Fundus Photographs in Patients With Branch Retinal Vein Occlusion
Authors: Miao Jinxin , Yu Jiale , Zou Wenjun , Su Na , Peng Zongyi , Wu Xinjing , Huang Junlong , Fang Yuan , Yuan Songtao , Xie Ping , Huang Kun , Chen Qiang , Hu Zizhong , Liu Qinghuai
Published: June 2022

Purpose

To develop artificial intelligence (AI)-based deep learning (DL) models for automatically detecting the ischemia type and the non-perfusion area (NPA) from color fundus photographs (CFPs) of patients with branch retinal vein occlusion (BRVO).

Methods

This was a retrospective analysis of 274 CFPs from patients diagnosed with BRVO. All DL models were trained using a deep convolutional neural network (CNN) based on 45 degree CFPs covering the fovea and the optic disk. We first trained a DL algorithm to identify BRVO patients with or without the necessity of retinal photocoagulation from 219 CFPs and validated the algorithm on 55 CFPs. Next, we trained another DL algorithm to segment NPA from 104 CFPs and validated it on 29 CFPs, in which the NPA was manually delineated by 3 experienced ophthalmologists according to fundus fluorescein angiography. Both DL models have been cross-validated 5-fold. The recall, precision, accuracy, and area under the curve (AUC) were used to evaluate the DL models in comparison with three types of independent ophthalmologists of different seniority.

Results

In the first DL model, the recall, precision, accuracy, and area under the curve (AUC) were 0.75 ± 0.08, 0.80 ± 0.07, 0.79 ± 0.02, and 0.82 ± 0.03, respectively, for predicting the necessity of laser photocoagulation for BRVO CFPs. The second DL model was able to segment NPA in CFPs of BRVO with an AUC of 0.96 ± 0.02. The recall, precision, and accuracy for segmenting NPA was 0.74 ± 0.05, 0.87 ± 0.02, and 0.89 ± 0.02, respectively. The performance of the second DL model was nearly comparable with the senior doctors and significantly better than the residents.

Conclusion

These results indicate that the DL models can directly identify and segment retinal NPA from the CFPs of patients with BRVO, which can further guide laser photocoagulation. Further research is needed to identify NPA of the peripheral retina in BRVO, or other diseases, such as diabetic retinopathy.
Cryptogenic Organizing Pneumonia Complicated With Cutaneous Disseminated Nocardia Infection: A Case Report and Literature Review
Authors: Wei Zhijing , Bao Pengchen , Wang Tianle , Wang Wei , Li Wen-Yang
Published: June 2022

Nocardia disease is a rare opportunistic infection that usually occurs in individuals with solid organ transplantation, malignant tumors, human immunodeficiency virus (HIV) infection, or chronic lung disease history. Here, we reported a rare case of cryptogenic organizing pneumonia (COP) combined with disseminated Nocardia infection. A 75-year-old man was admitted to the respiratory department due to weakness and poor appetite for 3 months. The chest CT scan showed dense patchy shadows in the dorsal lower lobe of both lungs. After the transbronchial lung biopsy, the histopathological findings supported the diagnosis of COP. During the period of glucocorticoid reduction (oral methylprednisolone tablets 24 mg one time a day), the patient presented with masses on the back and bilateral upper limbs and intermittent fever for 3 days. After admission, the patient underwent a series of examinations and an ultrasound puncture of the mass. The puncture fluid was caseous necrosis, which was confirmed to be Nocardia infection after bacterial culture, so the diagnosis was disseminated Nocardia infection. After 13 days of admission, the patient developed a headache, accompanied by decreased visual acuity and blurred vision. An imaging (enhanced brain CT) examination revealed intracranial space-occupying lesions. The neurosurgeon was consulted and performed transcranial abscess puncture and drainage, intravenous antibiotics (meropenem, etc.) for 2 months, and trimethoprim/sulfamethoxazole (TMP-SMX) for 6 months. The patient was followed up for 3 years and has remained relapse-free. The mortality rate of disseminated Nocardia infection is as high as 85%, especially when combined with brain abscesses. Therefore, timely diagnosis and correct treatment are crucial for the prevention of fatal consequences. The report of this case can enable more patients to receive early diagnosis and effective treatment, so as to obtain a satisfied prognosis.