bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of metabolic control on all-cause mortality in a nationwide cohort of patients with diabetes from Colombia
Authors: Mendivil Carlos O. , Amaya-Montoya Mateo , Hernández-Vargas Juliana Alexandra , Ramírez-García Nathaly , Herrera-Parra Lina Johana , Guatibonza-García Valentina , Romero-Díaz Camila , Pérez-Londoño Agustín , Acuña-Merchán Lizbeth
Published: January 2023

Objective

The magnitude of the mortality benefit conferred by good integral metabolic control in diabetes in not sufficiently known, especially among Latin American patients. We prospectively studied the association between sustained control of blood glucose (HbA1c<7%), systolic blood pressure (SBP) (<130 mmHg) and LDL (LDLc, <100mg/dL) and non-HDL (non-HDLc, <130 mg/dL) cholesterol, and death from any cause among all adult patients with diagnosed diabetes in Colombia.

Methods

We retrospectively analyzed data from a nationwide, centralized, mandatory registry of all patients with diagnosed diabetes assisted by the Colombian health system between July 1, 2015, and June 30, 2019. We estimated the associations of sustained achievement of each goal, and of the joint triple goal (HbA1c + SBP + LDLc) with all-cause death. Associations were assessed after adjustment for sex, age, race, insurance type and BMI in multivariable logistic models.

Results

We studied 1 352 846 people with diabetes. Sustained SBP (OR 0.42 [0.41-0.43]), HbA1c (OR 0.25 [0.24-0.26]) and LDLc (OR 0.28 [0.27-0.29]) control had strong negative associations with death. Moreover, among the 5.4% of participants who achieved joint, sustained metabolic control, the OR for death was 0.19 (0.18-0.21). Importantly, the impact of sustained, joint metabolic control was significantly smaller for patients of black race compared to other races (OR 0.31 [0.23-0.43] versus 0.18 [0.17-0.20], p-value for interaction <0.001), mostly at the expense of a smaller impact of LDLc control. The results were similar across body-mass index categories.

Conclusions

Sustained and simultaneous metabolic control was associated with remarkably lower odds of death.
Elafin is related to immune infiltration and could predict the poor prognosis in ovarian cancer
Authors: Lu Weiyu , Xie Biao , Tan Guangqing , Dai Wanying , Ren Jingyi , Pervaz Sadaf , Li Kun , Li Fangfang , Wang Yingxiong , Wang Meijiao
Published: January 2023

Background

Ovarian cancer (OC) is the most lethal gynecologic malignancy, yet the clinical results for OC patients are still variable. Therefore, we examined how elafin expression affects the patients’ prognoses and immunotherapy responses in OC, which may facilitate treatment selection and improve prognosis.

Methods

The elafin mRNA expression profile was downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus. Elafin’s prognostic potential and its relationship with clinical variables were investigated using Kaplan–Meier survival curves, time-dependent receiver operating characteristic curves as well as univariate and multivariate Cox regression models. As validation, protein expression in the tumor and adjacent tissues of OC patients was investigated by using immunohistochemistry (IHC). Comprehensive analyses were then conducted to explore the correlation between immune infiltration and elafin expression.

Results

A higher mRNA expression of elafin was associated with an unfavorable prognosis in TCGA cohort and was validated in GSE31245 and IHC. Moreover, elafin was indicated as an independent risk factor for OC. A significantly higher protein expression of elafin was detected in the adjacent tissues of OC patients with shorter overall survival (OS). The immune-related pathways were mainly enriched in the high-elafin-mRNA-expression group. However, the mRNA expression of elafin was favorably correlated with indicators of the immune filtration and immunotherapy response, which also proved better immunotherapy outcomes.

Conclusion

The high elafin expression was associated with an unfavorable OS, while it also indicated better immunotherapy responses. Thus, the detection of elafin is beneficial to diagnosis and treatment selection.
Hybrid kernel search and particle swarm optimization with Cauchy perturbation for economic emission load dispatch with valve point effect
Authors: Dong Ruyi , Ma Long , Chen Huiling , Heidari Ali Asghar , Liang Guoxi
Published: January 2023

Due to growing concerns over environmental protection, economic and environmentally responsible power dispatching has become a hot topic in the field of power system control. Multi-objective optimization minimizes fuel costs and pollution emissions without violating operational constraints. To solve this problem, the MOP is decomposed into individual objects via the weighted sum method, and Newton’s method is used to tackle equality constraints iteratively. To this end, a hybrid algorithm (HKSOPSO-CP) based on kernel search optimization (KSO) and particle swarm optimization (PSO) with Cauchy perturbation is proposed in this paper. An experiment with 23 CEC benchmark functions shows that HKSOPSO-CP offers better performance compared with various popular algorithms proposed in recent years. When employed to solve the IEEE standard economic emission dispatch (EED) problems with 6, 10, 40, and 110 units, the proposed HKSOPSO-CP algorithm produces results indicating a better trade-off between the objectives relating to fuel costs and emissions compared to other algorithms that have recently been reported on in the literature.
Backstepping based real twisting sliding mode control for photovoltaic system
Authors: Ullah Sahib , Malik Sarmad Majeed , Sun Yingyun , Numan Muhammad , Asif Mansoor , Hu Junjie , Bodla Muhammad Kamran
Published: January 2023

Renewable energy sources tied to a utility grid require non-linear control algorithms to provide an efficient and stable output under different operating conditions. The maximum power point tracking (MPPT) approach is necessary for power generation due to non-linear behavior of photovoltaic (PV) power plants. In changing environmental and partial shading conditions, the standard MPPT methods may lead to abnormal results. In this paper, a backstepping based real twisting sliding mode MPPT control is proposed for the PV-battery system where maximum available power is extracted by tracking PV voltage. Moreover, a direct sliding mode control is proposed for battery-integrated buck boost converter for voltage regulation. Reference sliding surface is generated through linear interpolation based on the predicted maximum power point PV voltage. The proposed MPPT strategy is tested against variations of irradiance, temperature, and load. Simulation results highlight superior tracking performance, reduced chattering, and oscillations of this technique over existing models.
Distributionally robust transactive control for active distribution systems with SOP-connected multi-microgrids
Authors: Yin Haojuntao , Yang Xiaodong , Zhang Youbing , Yang Xin , Guo Wenzhang , Lu Junjie
Published: January 2023

The increasing demand for distributed energy and active load increases the risk of voltage violations in active distribution systems. This paper proposes a distributionally robust transactive control method for local energy trading and network operation management of active distribution systems with interconnected microgrids. In particular, the emerging SOP technology is used for the flexible connection of the multi-microgrids (MMGs). First, the local energy interactive market between distribution network operator (DNO) and regional microgrids is constructed to simultaneously solve the economic and security problems of distribution networks considering the energy trading scenarios and various operational constraints. Then, the dual relaxation technique is used to transform the two-layer structure model into a single-layer model. Furthermore, the single-layer game model is further transformed into a two-stage distributed robust problem considering the uncertainties of load demand and renewable power outputs, and the second stage of the problem is decomposed into multiple parallel subproblems without dual information. Finally, numerical simulations on IEEE-33 test system verify the advantages and effectiveness of the proposed method.
A new approach for uncertainty quantification in predictor-corrector quasi-static Monte Carlo transient simulation
Authors: Oh Taesuk , Kim Inyup , Kim Yonghee
Published: January 2023

Two different approaches are widely accepted for transient Monte Carlo (MC) simulation namely the Dynamic Monte Carlo (DMC) and the Predictor-Corrector Quasi-Static Monte Carlo (PCQS-MC). The MC transport code iMC developed at the Korea Advanced Institute of Science and Technology incorporates both approaches. In this paper, an original method for properly assessing the uncertainty of PCQS-MC is proposed and demonstrated using the iMC code. A detailed description of applying the PCQS method for transient MC calculation is presented with an emphasis on the origins of PCQS-MC uncertainties. The implementation of a quasi-static method, i.e., calculation of point-kinetics (PK) parameters, incurs an additional uncertainty for PCQS-MC calculation alongside the conventional stochastic MC uncertainty. Such quasi-static treatment-driven stochasticity cannot be recognized through the conventional MC sampling scheme, insinuating a significant underestimation of uncertainty without proper measures. To verify the findings, null-transient simulations have been performed for GODIVA and C5G7 benchmarks, where the former and latter problems require continuous and multi-group energy treatment respectively. For an improved uncertainty evaluation, a new sampling scheme referred to as the PK-sampling scheme is proposed where cycle-wise PK correction is made. Proper estimation of uncertainty can be made from the heap of cycle-wise corrected power through a unique screening process based on the null hypothesis testing. The proposed PK sampling scheme is tested for C5G7-TD transient benchmarks using iMC where the result plainly attests to the effectiveness of the new sampling approach.
Numerical simulation of heat and mass transfer of a wall containing micro-encapsulated phase change concrete (PCC)
Authors: Lajimi Nour , Ben Taher Nour , Boukadida Noureddine
Published: January 2023

Before planning to equip buildings with energy systems, it is essential to first understand and control the behavior of the premises (via control of heat and water transfer phenomena) (air conditioners, heat pumps, heat exchangers, etc.). Given the amount of solar radiation to which it is exposed in summer and its significant contribution to energy loss in winter, the thermal insulation of the ceiling appears effective. The objective of this work is to study the heat and mass transfer through a ceiling wall containing micro-encapsulated phase change materials under realistic climatic conditions based on meteorological data in Tunisia. This article is about a numerical study that uses software (DIGITAL Visual FORTRAN 95) to predict the effect of incorporating a layer of PCM on thermal behavior, mass, and occupant thermal comfort, as well as energy consumption for summer and winter periods.
Rare earth elements in aeolian loess sediments from Menyuan Basin, northeastern Tibetan plateau: Implications for provenance
Authors: Shi Yunkun , E Chongyi , Peng Qiang , Zhang Zhaokang , Zhang Jing , Yan Wenting , Xu Chunxia
Published: January 2023

Aeolian loess is a widespread deposit in mid-latitude arid and semiarid regions that has been extensively investigated in arid Central Asia and the Chinese Loess Plateau. The northeastern Tibetan Plateau is crucial to the release, transport, and accumulation of aeolian sediments because of its vast environmental differences, but relatively little research has been conducted on the loess here. To further deepen our understanding of the loess source in this region, we selected the Menyuan Basin as the study area for this loess tracing research. Through our investigation of the indicators and distribution characteristics of rare earth elements in the Yahecun (YHC) loess-paleosol profile of the Menyuan Basin, the following conclusions were drawn: 1) the indices and distribution curves of rare earth elements in the diverse strata of the YHC profile were not significantly distinct and were comparable to those of loess from other locations in northwestern China, revealing a general association with loess in arid northwestern China; 2) the influence of chemical weathering and particle diameter on rare earth elements in the loess of the study area was minimal, and Menyuan loess rare earth elements contained considerable information regarding their source; and 3) a comparison of the (La/Yb)N, δEu, (La/Sm)N, and (Gd/Yb)N parameters of potential source areas indicates that arid Central Asia, dominated by the Qaidam Desert, is the primary source area of the Menyuan loess, and dust particles released from these deserts are transported to the Menyuan Basin by the Westerlies and deposited to form loess. Additionally, the Badain Jaran Desert is an essential source of material for the Menyuan loess by winter winds, and some Tengger Desert materials are also transported to the Menyuan Basin by winter winds, but the material transported from the Tengger Desert has a negligible contribution.
Embodied carbon transfers and employment-economic spillover effects in China’s inter-provincial trade
Authors: Yang Dewei , Guo Ruifang , O’Connor Patrick , Zhou Tian , Zhang Shuai , Meng Haishan , Wan Min , Dai Chunyan , Ma Weijing
Published: January 2023

Understanding the embodied carbon transfer in inter-provincial trade and its employment-economic spillover effects is of crucial value in achieving carbon equity management. Surprisingly, few studies have focused on the intrinsic relationship between embodied carbon, embodied GDP, and embodied employment in iinter-provincial trade and its equity implications. Based on the 2012 and 2017 multi-regional input-output tables, our study of inter-provincial trade in 30 Chinese provinces shows that: 1) net outflows of embodied carbon were concentrated in the Beijing-Tianjin region and the eastern and southern coastal regions, while net inflows were in the central and northwestern regions; 2) embodied carbon, GDP, and employment were characterized by nearby transfer, complementary energy economy, and asymmetric transfers in and out; and 3) western provinces, which relied heavily on traditional energy and heavy chemical industries, gained a competitive disadvantage implying by the internal relationship between net transfers of embodied carbon, GDP, and employment. To mitigate the inequity of inter-provincial carbon trade, top-down climate goals must be aligned with bottom-up socio-economic incentives to achieve balanced regional development and improved public welfare.
Regime of fluvial phosphorus constituted by sediment
Authors: Li Huali , Zhou Jianjun , Zhang Man
Published: January 2023

Phosphorus (P) is a crucial macronutrient, and recently a venture agent of pollutant, in aquatic systems worldwide. Most of P circulates with sediment through rivers, and the relationship between P and sediment is the basis for understanding the biogeochemical processes in rivers. Although studies of fluvial P have been carried out at specific sites and for particular problems, the general regime by which sediment affects P recirculation still warrants attention. In this study, a series of water samples were collected from six different rivers in China whose sediment concentration and size distribution vary widely and their P properties were analyzed in the laboratory. From this analysis of field samples, a highly consistent comet shaped pattern of sediment effects on P is revealed, i.e., generally the range of the concentration of total P has a diverge-converge trend as the sediment concentration increases. It is further supported by examining the strictly composed samples from P adsorption experiments. Furthermore, case analyses were performed on the basis of the above relationships to illustrate the impact of sediment on P cycling in rivers. The results can infer the following: 1) There is a strong positive correlation between total P and sediment concentration, indicating that sediment is a crucial agent in the movement and fate of P. 2) The negative correlation between dissolved P and sediment concentration indicates a buffering effect of sediment, especially fine sediment, on dissolved P, interpreting the intricate phenomena of increased dissolved P concentration caused by sediment reduction. Hence, natural sediment has the prevailing advantage in moderating the water quality of rivers, which is directly relevant to mitigating the present pollution and eutrophication of waters. 3) River damming causes a P blockage tendency, altering the fluvial nourishment to contamination in the river.
Does green financial infrastructure promote the improvement and convergence of regional carbon emission efficiency? Based on provincial data of China
Authors: Zhang Haijun , Wang Jintao , Xu Zhicang
Published: January 2023

The level of green financial infrastructure is measured using a symbiometric model with the Chinese provincial panel data from 2008 to 2020, and also the carbon emission efficiency is measured using the super-efficient SBM-DEA model with the carbon emission data at the provincial level. This paper tests the carbon emission efficiency improvement and convergence effects of green financial infrastructure using fixed-effects models, non-dynamic panel threshold models and spatial econometric models, while considering the role of environmental regulation in the process. It is found that green financial infrastructure significantly contributes to the improvement of carbon emission efficiency and accelerates the convergence rate of carbon emission efficiency between regions; the carbon emission efficiency improvement and convergence effects of green financial infrastructure are influenced by the intensity of environmental regulation, and we point out that either too strong or too weak environmental regulation will weaken the effectiveness of green financial infrastructure, which means there is a significant threshold effect; the spatial durbin model shows that the effect of green financial infrastructure on carbon emission efficiency has a spatial spillover effect of “neighbors as partners”, that is, while green financial infrastructure promotes the improvement of carbon emission efficiency in the region, it also helps to promote the improvement of carbon emission efficiency in the neighboring regions. Therefore, China should accelerate the improvement of the green financial infrastructure system, improve the carbon emission rights market trading system, enhance the effectiveness of environmental regulation, and strengthen regional economic cooperation, so as to empower the development of low-carbon and green economic transformation.
Effects of urbanization on multiple human perceived temperatures in South China
Authors: Lin Lijie , Guo Meiyu
Published: January 2023

Under the combined effects of global warming and local human activities such as urbanization, increasing populations are exposed to the threat of extreme heat events. While the effects of regional urbanization on the changes in air temperature and its extremes have been well studied, the effects on mean and extreme human perceived temperatures (HPT) are still to be explored. Based on a dynamic meteorological station classification approach, this study quantitatively assessed the impacts and relative contribution of urbanization on the mean and extreme human perceived temperatures in South China by analyzing ten different human perceived temperatures indicators and taking Guangdong Province as an example. It was found that for all human perceived temperatures indicators, the mean human perceived temperatures and the frequency of extreme human perceived temperatures events in South China notably increased from 1971 to 2020, especially in the regions with comparatively higher levels of local urbanization (e.g., the Pearl River Delta). Urbanization contributed significantly to the long-term changes in both mean and extreme human perceived temperatures in Guangdong. On average, the relative contributions of urbanization to the total increases in mean human perceived temperatures and the frequency of extreme human perceived temperatures events were 15.5% and 15.1%, respectively. These contributions vary across different human perceived temperatures indicators, and the urbanization contributions to the human perceived temperatures indicators that consider the combined effects of wind speed were even higher than those merely related to near-surface air temperature and humidity. Among different seasons, the contributions of urbanization to mean and extreme human perceived temperatures in both fall and winter were greater than that in spring and summer. The findings reported here provide scientific advice for governments’ policy-making and adaption for human-perceived thermal comfort in subtropical humid climate zones.
What is the relationship between ecosystem services and farmers’ livelihoods? Based on measuring the contribution of ecosystem services to farmers’ livelihoods
Authors: Zhou Lilei , Guan Dongjie , Sun Lingli , He Xiujuan , Chen Maolin , Zhang Yongchuan , Zhou Lianjie
Published: January 2023

The relationships between ecosystem services and farmers’ livelihoods are important for ecological and livelihood sustainability. In this paper, Chongqing was picked up as a case to elucidate the contribution of ecosystem services to farmers’ livelihoods. First, we constructed a DPSIR (driver, pressure, state, impact and response) framework of ecosystem services and farmers’ livelihoods through participatory farmers’ livelihoods surveys and empirical data from the literature. Then, a 48-node Bayesian network model were used to explore the explicit and implicit impacts of both ecosystem services and farmers’ livelihoods, and to determine the key factors. Finally, we analyzed the contribution of ecosystem services to different types of farmers’ livelihoods. The results showed that ecosystem services have a significant impact on the farmers’ livelihoods. The probabilities of high state for ecosystem services and livelihood outcomes were 17.6% and 30.7%, respectively. While the probabilities of medium state were 51.2% and 45.4%, respectively. Particularly for low-income farmers, the impact on them increased with the increasing of ecosystem services (such as esthetic landscapes and food production). For different types of farming households, the most important contributor of ecosystem services-related income were pure farming households, part-time farming households and nonfarming households, accounting for 77.3%, 36.3%, and 14.8% of the total average annual household income, respectively. Our findings suggested that in promoting sustainable management of ecosystems, the contribution of ecosystem services to farmers’ livelihoods and their impact on farm income and the ecosystem services value should be considered.
Draft genome assembly for the colombian freshwater bocachico fish, Prochilodus magdalenae
Authors: Yepes-Blandón Jonny Andrés , Bian Chao , Benítez-Galeano María José , Aristizabal-Regino Jorge Luis , Estrada-Posada Ana Lucía , Mir Daiana , Vásquez-Machado Gersson , Atencio-García Víctor Julio , Shi Qiong , Rodríguez-Osorio Nélida
Published: January 2023

We report the first draft genome assembly forProchilodus magdalenae, the leading representative species of the Prochilodontidae family in Colombia. This 1.2-Gb assembly, with a GC content of 42.0% and a repetitive content of around 31.0%, is in the range of previously reported characid species genomes. Annotation identified 34,725 nuclear genes, and BUSCO completeness value was 94.9%. Gene ontology and primary metabolic pathway annotations indicate similar gene profiles forP. magdalenaeand the closest species with annotated genomes: blind cave fish (Astyanax mexicanus) and red piranha (Pygocentrus nattereri). A comparative analysis showed similar genome traits to other characid species. The fully sequenced and annotated mitochondrial genome reproduces the taxonomic classification ofP. magdalenaeand confirms the low mitochondrial genetic divergence inside theProchilodusgenus. Phylogenomic analysis, using nuclear single-copy orthologous genes, also confirmed the evolutionary position of the species. This genome assembly provides a high-resolution genetic resource for sustainableP. magdalenaemanagement in Colombia and, as the first genome assembly for the Prochilodontidae family, will contribute to fish genomics throughout South America.
Integrative analysis of Iso-Seq and RNA-seq reveals dynamic changes of alternative promoter, alternative splicing and alternative polyadenylation during Angiotensin II-induced senescence in rat primary aortic endothelial cells
Authors: Wen Haimei , Chen Wei , Chen Yu , Wei Gang , Ni Ting
Published: January 2023

In eukaryotes, alternative promoter (AP), alternative splicing (AS), and alternative polyadenylation (APA) are three crucial regulatory mechanisms that modulate message RNA (mRNA) diversity. Although AP, AS and APA are involved in diverse biological processess, whether they have dynamic changes in Angiotensin II (Ang II) induced senescence in rat primary aortic endothelial cells (RAECs), an important cellular model for studying cardiovascular disease, remains unclear. Here we integrated both PacBio single-molecule long-read isoform sequencing (Iso-Seq) and Illumina short-read RNA sequencing (RNA-seq) to analyze the changes of AP, AS and APA in Ang II-induced senescent RAECs. Iso-Seq generated 36,278 isoforms from 10,145 gene loci and 65.81% of these isoforms are novel, which were further cross-validated by public data obtained by other techonologies such as CAGE, PolyA-Seq and 3′READS. APA contributed most to novel isoforms, followed by AS and AP. Further investigation showed that AP, AS and APA could all contribute to the regulation of isoform, but AS has more dynamic changes compared to AP and APA upon Ang II stimulation. Genes undergoing AP, AS and APA in Ang II-treated cells are enriched in various pathways related to aging or senescence, suggesting that these molecular changes are involved in functional alterations during Ang II-induced senescence. Together, the present study largely improved the annotation of rat genome and revealed gene expression changes at isoform level, extending the understanding of the complexity of gene regulation in Ang II-treated RAECs, and also provided novel clues for discovering the regulatory mechanism undelying Ang II caused vascular senescence and diseases.
A review of ancestrality and admixture in Latin America and the caribbean focusing on native American and African descendant populations
Authors: De Oliveira Thais C. , Secolin Rodrigo , Lopes-Cendes Iscia
Published: January 2023

Genomics can reveal essential features about the demographic evolution of a population that may not be apparent from historical elements. In recent years, there has been a significant increase in the number of studies applying genomic epidemiological approaches to understand the genetic structure and diversity of human populations in the context of demographic history and for implementing precision medicine. These efforts have traditionally been applied predominantly to populations of European origin. More recently, initiatives in the United States and Africa are including more diverse populations, establishing new horizons for research in human populations with African and/or Native ancestries. Still, even in the most recent projects, the under-representation of genomic data from Latin America and the Caribbean (LAC) is remarkable. In addition, because the region presents the most recent global miscegenation, genomics data from LAC may add relevant information to understand population admixture better. Admixture in LAC started during the colonial period, in the 15th century, with intense miscegenation between European settlers, mainly from Portugal and Spain, with local indigenous and sub-Saharan Africans brought through the slave trade. Since, there are descendants of formerly enslaved and Native American populations in the LAC territory; they are considered vulnerable populations because of their history and current living conditions. In this context, studying LAC Native American and African descendant populations is important for several reasons. First, studying human populations from different origins makes it possible to understand the diversity of the human genome better. Second, it also has an immediate application to these populations, such as empowering communities with the knowledge of their ancestral origins. Furthermore, because knowledge of the population genomic structure is an essential requirement for implementing genomic medicine and precision health practices, population genomics studies may ensure that these communities have access to genomic information for risk assessment, prevention, and the delivery of optimized treatment; thus, helping to reduce inequalities in the Western Hemisphere. Hoping to set the stage for future studies, we review different aspects related to genetic and genomic research in vulnerable populations from LAC countries.
The association of BTLA gene polymorphisms with non-small lung cancer risk in smokers and never-smokers
Authors: Andrzejczak Anna , Partyka Anna , Wiśniewski Andrzej , Porębska Irena , Pawełczyk Konrad , Ptaszkowski Kuba , Kuśnierczyk Piotr , Jasek Monika , Karabon Lidia
Published: January 2023

Introduction

Lung cancer is the predominant cause of death among cancer patients and non-small cell lung cancer (NSCLC) is the most common type. Cigarette smoking is the prevailing risk factor for NSCLC, nevertheless, this cancer is also diagnosed in never-smokers. B and T lymphocyte attenuator (BTLA) belongs to immunological checkpoints which are key regulatory molecules of the immune response. A growing body of evidence highlights the important role of BTLA in cancer. In our previous studies, we showed a significant association between BTLA gene variants and susceptibility to chronic lymphoblastic leukemia and renal cell carcinoma in the Polish population. The present study aimed to analyze the impact of BTLA polymorphic variants on the susceptibility to NSCLC and NSCLC patients’ overall survival (OS).

Methods

Using TaqMan probes we genotyped seven BTLA single-nucleotide polymorphisms (SNPs): rs2705511, rs1982809, rs9288952, rs9288953, rs1844089, rs11921669 and rs2633582 with the use of ViiA 7 Real-Time PCR System.

Results

We found that rs1982809 within BTLA is associated with NSCLC risk, where carriers of rs1982809G allele (AG+GG genotypes) were more frequent in patients compared to controls. In subgroup analyses, we also noticed that rs1982809G carriers are significantly overrepresented in never-smokers, but not in smokers compared to controls. Additionally, the global distribution of the haplotypes differed between the never-smokers and smokers, where haplotypes A G G C A, C G A C G, and C G A T G were more frequent in never-smoking patients. Furthermore, the presence rs1982809G (AG+GG genotypes) allele as well as the presence of rs9288953T allele (CT+TT genotypes) increased NSCLC risk in females’ patients. After stratification by histological type, we noticed that rs1982809G and rs2705511C carriers were more frequent among adenocarcinoma patients. Moreover, rs1982809G and rs2705511C correlated with the more advanced stages of NSCLC (stage II and III), but not with stage IV. Furthermore, we showed that rs2705511 and rs1982809 significantly modified OS, while rs9288952 tend to be associated with patients’ survival.

Conclusion

Our results indicate that BTLA polymorphic variants may be considered low penetrating risk factors for NSCLC especially in never-smokers, and in females, and are associated with OS of NSCLC patients.
The role of innate immune cells in the tumor microenvironment and research progress in anti-tumor therapy
Authors: Lu Chenglin , Liu Ying , Ali Nasra Mohamoud , Zhang Bin , Cui Xiaonan
Published: January 2023

Innate immune cells in the tumor microenvironment (TME) mainly include macrophages, neutrophils, natural killer cells, dendritic cells and bone marrow derived suppressor cells. They play an anti-tumor or pro-tumor role by secreting various cytokines, chemokines and other factors, and determine the occurrence and development of tumors. Comprehending the role of innate immune cells in tumorigenesis and progression can help improve therapeutic approaches targeting innate immune cells in the TME, increasing the likelihood of favorable prognosis. In this review, we discussed the cell biology of innate immune cells, their role in tumorigenesis and development, and the current status of innate immune cell-based immunotherapy, in order to provide an overview for future research lines and clinical trials.
The antitumor activity of human Vγ9Vδ2 T cells is impaired by TGF-β through significant phenotype, transcriptomic and metabolic changes
Authors: Rafia Chirine , Loizeau Clément , Renoult Ophélie , Harly Christelle , Pecqueur Claire , Joalland Noémie , Scotet Emmanuel
Published: January 2023

Despite significant advances, the eradication of cancer remains a clinical challenge which justifies the urgent exploration of additional therapeutic strategies such as immunotherapies. Human peripheral Vγ9Vδ2 T cells represent an attractive candidate subset for designing safe, feasible and effective adoptive T cell transfer-based therapies. However, following their infiltration within tumors, γδ T cells are exposed to various regulating constituents and signals from the tumor microenvironment (TME), which severely alter their antitumor functions. Here, we show that TGF-β, whose elevated production in some solid tumors is linked to a poor prognosis, interferes with the antigenic activation of human Vγ9Vδ2 T cells in vitro. This regulatory cytokine strongly impairs their cytolytic activity, which is accompanied by the induction of particular phenotypic, transcriptomic and metabolic changes. Collectively, these observations provide information for better understanding and targeting the impact of TME components to regulate the antitumor activity of human T cell effectors.
Single-cell analysis of myeloid cells in HPV+ tonsillar cancer
Authors: Jimenez David Gomez , Altunbulakli Can , Swoboda Sabine , Sobti Aastha , Askmyr David , Ali Ashfaq , Greiff Lennart , Lindstedt Malin
Published: January 2023

The incidence of human papillomavirus-positive (HPV+) tonsillar cancer has been sharply rising during the last decades. Myeloid cells represent an appropriate therapeutic target due to their proximity to virus-infected tumor cells, and their ability to orchestrate antigen-specific immunity, within the tonsil. However, the interrelationship of steady-state and inflammatory myeloid cell subsets, and their impact on patient survival remains unexplored. Here, we used single-cell RNA-sequencing to map the myeloid compartment in HPV+ tonsillar cancer. We observed an expansion of the myeloid compartment in HPV+ tonsillar cancer, accompanied by interferon-induced cellular responses both in dendritic cells (DCs) and monocyte-macrophages. Our analysis unveiled the existence of four DC lineages, two macrophage polarization processes, and their sequential maturation profiles. Within the DC lineages, we described a balance shift in the frequency of progenitor and mature cDC favoring the cDC1 lineage in detriment of cDC2s. Furthermore, we observed that all DC lineages apart from DC5s matured into a common activated DC transcriptional program involving upregulation of interferon-inducible genes. In turn, the monocyte-macrophage lineage was subjected to early monocyte polarization events, which give rise to either interferon-activated or CXCL-producing macrophages, the latter enriched in advanced tumor stages. We validated the existence of most of the single-cell RNA-seq clusters using 26-plex flow cytometry, and described a positive impact of cDC1 and interferon-activated DCs and macrophages on patient survival using gene signature scoring. The current study contributes to the understanding of myeloid ontogeny and dynamics in HPV-driven tonsillar cancer, and highlights myeloid biomarkers that can be used to assess patient prognosis.
The Vacc-SeqQC project: Benchmarking RNA-Seq for clinical vaccine studies
Authors: Goll Johannes B. , Bosinger Steven E. , Jensen Travis L. , Walum Hasse , Grimes Tyler , Tharp Gregory K. , Natrajan Muktha S. , Blazevic Azra , Head Richard D. , Gelber Casey E. , Steenbergen Kristen J. , Patel Nirav B. , Sanz Patrick , Rouphael Nadine G. , Anderson Evan J. , Mulligan Mark J. , Hoft Daniel F.
Published: January 2023

Introduction

Over the last decade, the field of systems vaccinology has emerged, in which high throughput transcriptomics and other omics assays are used to probe changes of the innate and adaptive immune system in response to vaccination. The goal of this study was to benchmark key technical and analytical parameters of RNA sequencing (RNA-seq) in the context of a multi-site, double-blind randomized vaccine clinical trial.

Methods

We collected longitudinal peripheral blood mononuclear cell (PBMC) samples from 10 subjects before and after vaccination with a live attenuated Francisella tularensis vaccine and performed RNA-Seq at two different sites using aliquots from the same sample to generate two replicate datasets (5 time points for 50 samples each). We evaluated the impact of (i) filtering lowly-expressed genes, (ii) using external RNA controls, (iii) fold change and false discovery rate (FDR) filtering, (iv) read length, and (v) sequencing depth on differential expressed genes (DEGs) concordance between replicate datasets. Using synthetic mRNA spike-ins, we developed a method for empirically establishing minimal read-count thresholds for maintaining fold change accuracy on a per-experiment basis. We defined a reference PBMC transcriptome by pooling sequence data and established the impact of sequencing depth and gene filtering on transcriptome representation. Lastly, we modeled statistical power to detect DEGs for a range of sample sizes, effect sizes, and sequencing depths.

Results and Discussion

Our results showed that (i) filtering lowly-expressed genes is recommended to improve fold-change accuracy and inter-site agreement, if possible guided by mRNA spike-ins (ii) read length did not have a major impact on DEG detection, (iii) applying fold-change cutoffs for DEG detection reduced inter-set agreement and should be used with caution, if at all, (iv) reduction in sequencing depth had a minimal impact on statistical power but reduced the identifiable fraction of the PBMC transcriptome, (v) after sample size, effect size (i.e. the magnitude of fold change) was the most important driver of statistical power to detect DEG. The results from this study provide RNA sequencing benchmarks and guidelines for planning future similar vaccine studies.
A nomogram based on HBeAg, AST, and age to predict non-minimal liver inflammation in CHB patients with ALT <80 U/L
Authors: Zhang Lu , Bi Xiaoyue , Chen Xiaoxue , Zhang Luxue , Xiong Qiqiu , Cao Weihua , Lin Yanjie , Yang Liu , Jiang Tingting , Deng Wen , Wang Shiyu , Wu Shuling , Liu Ruyu , Gao Yuanjiao , Shen Ge , Chang Min , Hao Hongxiao , Xu Mengjiao , Hu Leiping , Lu Yao , Li Minghui , Xie Yao
Published: January 2023

Objective

Precise assessment of liver inflammation in untreated hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B virus (HBV) infection can determine when to initiate antiviral therapy. The aim of this study was to develop and validate a nomogram model for the prediction of non-minimal liver inflammation based on liver pathological injuries combined with age and alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatitis B surface antigen (HBsAg), HBeAg, and HBV DNA quantification.

Methods

We retrospectively included 735 HBeAg-positive chronic hepatitis B (CHB) patients with ALT < 80 U/L as the primary cohort and prospectively enrolled 196 patients as the validation cohort. Multivariate logistic regression analysis identified independent impact factors. A nomogram to predict significant liver inflammation was developed and validated.

Results

Multivariate logistic regression analysis showed that HBeAg, AST, and age were independent risk factors for predicting non-minimal liver inflammation in untreated CHB patients. The final formula for predicting non-minimal liver inflammation was Logit(P) = −1.99 − 0.68 × Log10HBeAg + 0.04 × Age + 0.06 × AST. A nomogram for the prediction of non-minimal liver inflammation was established based on the results from the multivariate analysis. The predicted probability of the model being consistent with the actual probability was validated by the calibration curves, showing the best agreement in both the primary and validation cohorts. The C-index was 0.767 (95%CI = 0.734–0.802) in the primary cohort and 0.749 (95%CI = 0.681–0.817) in the prospective validation cohort.

Conclusions

The nomogram based on HBeAg, AST, and age might help predict non-minimal liver inflammation in HBeAg-positive CHB patients with ALT < 80 U/L, which is practical and easy to use for clinicians.
Identification of gene signatures associated with ulcerative colitis and the association with immune infiltrates in colon cancer
Authors: Pan Zhaoji , Lin Hao , Fu Yanyan , Zeng Fanpeng , Gu Feng , Niu Guoping , Fang Jian , Gu Bing
Published: January 2023

Background

Inflammatory bowel diseases, including ulcerative colitis (UC) and Crohn’s disease, are some of the most common inflammatory disorders of the gastrointestinal tract. The dysfunction of the immune system in the intestines is suggested to be the underlying cause of the pathogenesis of UC. However, the mechanisms regulating these dysfunctional immune cells and inflammatory phenotypes are still unclear.

Methods

The differential expression analysis on microarray datasets were performed including GSE24287, GSE87466, GSE102133, and GSE107499, including 376 samples. “Gene Ontology” and “Kyoto Encyclopedia of Genes and Genomes” pathway enrichment analyses were conducted to identify the common differentially expressed genes (DEGs) in these datasets and explore their underlying biological mechanisms. Further algorithms like “Cell-type Identification by Estimating Relative Subsets of RNA Transcripts” were used to determine the infiltration status of immune cells in patients with UC. “Cytoscape” and “Gene Set Enrichment Analysis” were used to screen for hub genes and to investigate their biological mechanisms. The Tumor Immune Estimation Resource database was used to study the correlation between hub genes and infiltrating immune cells in patients with UC. A total of three hub genes, CCL3, MMP3, and TIMP1, were identified using Cytoscape.

Results

A positive correlation was observed between these hub genes and patients with active UC. These genes served as a biomarker for active UC. Moreover, a decrease in CCL3, MMP3, and TIMP1 expression was observed in the mucosa of the intestine of patients with active UC who responded to Golimumab therapy. In addition, results show a significant positive correlation between CCL3, MMP3, and TIMP1 expression and different immune cell types including dendritic cells, macrophages, CD8+ T cells, and neutrophils in patients with colon cancer. Moreover, CCL3, MMP3, and TIMP1 expression were strongly correlated with different immune cell markers.

Conclusion

Study results show the involvement of hub genes like CCL3, MMP3, and TIMP1 in the pathogenesis of UC. These genes could serve as a novel pharmacological regulator of UC. These could be used as a therapeutic target for treating patients with UC and may serve as biomarkers for immune cell infiltration in colon cancer.
Deep blue artificial intelligence for knowledge discovery of the intermediate ocean
Authors: Chen Ge , Huang Baoxiang , Yang Jie , Radenkovic Milena , Ge Linyao , Cao Chuanchuan , Chen Xiaoyan , Xia Linghui , Han Guiyan , Ma Ying
Published: January 2023

Oceans at a depth ranging from ~100 to ~1000-m (defined as the intermediate water here), though poorly understood compared to the sea surface, is a critical layer of the Earth system where many important oceanographic processes take place. Advances in ocean observation and computer technology have allowed ocean science to enter the era of big data (to be precise, big data for the surface layer, small data for the bottom layer, and the intermediate layer sits in between) and greatly promoted our understanding of near-surface ocean phenomena. During the past few decades, however, the intermediate ocean is also undergoing profound changes because of global warming, the research and prediction of which are of intensive concern. Due to the lack of three-dimensional ocean theories and field observations, how to remotely sense the intermediate ocean from space becomes a very attractive but challenging scientific issue. With the rapid development of the next generation of information technology, artificial intelligence (AI) has built a new bridge from data science to marine science (called Deep Blue AI, DBAI), which acts as a powerful weapon to extend the paradigm of modern oceanography in the era of the metaverse. This review first introduces the basic prior knowledge of water movement in the ~100 m ocean and vertical stratification within the ~1000-m depths as well as the data resources provided by satellite remote sensing, field observation, and model reanalysis for DBAI. Then, three universal DBAI methodologies, namely, associative statistical, physically informed, and mathematically driven neural networks, are elucidated in the context of intermediate ocean remote sensing. Finally, the unique advantages and potentials of DBAI in data mining and knowledge discovery are demonstrated in a top-down way of “surface-to-interior”viaseveral typical examples in physical and biological oceanography.