bluuebunny/crossref_metadata_2025 huggingface dataset:
Unravelling the Difference Between Men and Women in Post-CABG Survival
Authors: Schmidt Amand F. , Haitjema Saskia , Sartipy Ulrik , Holzmann Martin J. , Malenka David J. , Ross Cathy S. , van Gilst Wiek , Rouleau Jean L. , Meeder Annelijn M. , Baker Robert A. , Shiomi Hiroki , Kimura Takeshi , Tran Lavinia , Smith Julian A. , Reid Christopher M. , Asselbergs Folkert W. , den Ruijter Hester M.
Published: April 2022

Objectives

Women have a worse prognosis after coronary artery bypass grafting (CABG) surgery compared to men. We sought to quantify to what extent this difference in post-CABG survival could be attributed to sex itself, or whether this was mediated by difference between men and women at the time of intervention. Additionally, we explored to what extent these effects were homogenous across patient subgroups.

Methods

Time to all-cause mortality was available for 102,263 CABG patients, including 20,988 (21%) women, sourced through an individual participant data meta-analysis of five cohort studies. Difference between men and women in survival duration was assessed using Kaplan–Meier estimates, and Cox’s proportional hazards model.

Results

During a median follow-up of 5 years, 13,598 (13%) patients died, with women more likely to die than men: female HR 1.20 (95%CI 1.16; 1.25). We found that differences in patient characteristics at the time of CABG procedure mediated this sex effect, and accounting for these resulted in a neutral female HR 0.98 (95%CI 0.94; 1.02). Next we performed a priori defined subgroup analyses of the five most prominent mediators: age, creatinine, peripheral vascular disease, type 2 diabetes, and heart failure. We found that women without peripheral vascular disease (PVD) or women aged 70+, survived longer than men (interaction p-values 0.04 and 6 × 10–5, respectively), with an effect reversal in younger women.

Conclusion

Sex differences in post-CABG survival were readily explained by difference in patient characteristics and comorbidities. Pre-planned analyses revealed patient subgroups (aged 70+, or without PVD) of women that survived longer than men, and a subgroup of younger women with comparatively poorer survival.
Relationship Between Circulating MicroRNAs and Left Ventricular Hypertrophy in Hypertensive Patients
Authors: Lopes Elisangela C. P. , Paim Layde R. , Carvalho-Romano Luís F. R. S. , Marques Edmilson R. , Minin Eduarda O. Z. , Vegian Camila F. L. , Pio-Magalhães José A. , Velloso Lício A. , Coelho-Filho Otavio R. , Sposito Andrei C. , Matos-Souza José R. , Nadruz Wilson , Schreiber Roberto
Published: April 2022

Objective

Left ventricular hypertrophy (LVH) is a common complication of hypertension and microRNAs (miRNAs) are considered to play an important role in cardiac hypertrophy development. This study evaluated the relationship between circulating miRNAs and LVH in hypertensive patients.

Methods

Two cohorts [exploratory (n = 42) and validation (n = 297)] of hypertensive patients were evaluated by clinical, laboratory and echocardiography analysis. The serum expression of 754 miRNAs in the exploratory cohort and 6 miRNAs in the validation cohort was evaluated by the TaqMan OpenArray® system and quantitative polymerase chain reaction, respectively.

Results

Among the 754 analyzed miRNAs, ten miRNAs (miR-30a-5p, miR-let7c, miR-92a, miR-451, miR-145-5p, miR-185, miR-338, miR-296, miR-375, and miR-10) had differential expression between individuals with and without LVH in the exploratory cohort. Results of multivariable regression analysis adjusted for confounding variables showed that three miRNAs (miR-145-5p, miR-451, and miR-let7c) were independently associated with LVH and left ventricular mass index in the validation cohort. Functional enrichment analysis demonstrated that these three miRNAs can regulate various genes and pathways related to cardiac remodeling. Furthermore, in vitro experiments using cardiac myocytes demonstrated that miR-145-5p mimic transfection up-regulated the expression of brain and atrial natriuretic peptide genes, which are markers of cardiac hypertrophy, while anti-miR-145-5p transfection abrogated the expression of these genes in response to norepinephrine stimulus.

Conclusions

Our data demonstrated that circulating levels of several miRNAs, in particular miR-145-5p, miR-451, and let7c, were associated with LVH in hypertensive patients, indicating that these miRNAS may be potential circulating biomarkers or involved in hypertension-induced LV remodeling.
Foam Cells in Atherosclerosis: Novel Insights Into Its Origins, Consequences, and Molecular Mechanisms
Authors: Gui Yuzhou , Zheng Hongchao , Cao Richard Y.
Published: April 2022

Foam cells play a vital role in the initiation and development of atherosclerosis. This review aims to summarize the novel insights into the origins, consequences, and molecular mechanisms of foam cells in atherosclerotic plaques. Foam cells are originated from monocytes as well as from vascular smooth muscle cells (VSMC), stem/progenitor cells, and endothelium cells. Novel technologies including lineage tracing and single-cell RNA sequencing (scRNA-seq) have revolutionized our understanding of subtypes of monocyte- and VSMC-derived foam cells. By using scRNA-seq, three main clusters including resident-like, inflammatory, and triggering receptor expressed on myeloid cells-2 (Trem2hi) are identified as the major subtypes of monocyte-derived foam cells in atherosclerotic plaques. Foam cells undergo diverse pathways of programmed cell death including apoptosis, autophagy, necroptosis, and pyroptosis, contributing to the necrotic cores of atherosclerotic plaques. The formation of foam cells is affected by cholesterol uptake, efflux, and esterification. Novel mechanisms including nuclear receptors, non-coding RNAs, and gut microbiota have been discovered and investigated. Although the heterogeneity of monocytes and the complexity of non-coding RNAs make obstacles for targeting foam cells, further in-depth research and therapeutic exploration are needed for the better management of atherosclerosis.
Clinical Impact and Prognostic Role of Triglyceride to High-Density Lipoprotein Cholesterol Ratio in Patients With Chronic Coronary Syndromes at Very High Risk: Insights From the START Study
Authors: De Luca Leonardo , Temporelli Pier Luigi , Colivicchi Furio , Gonzini Lucio , Fasano Maria Luisa , Pantaleoni Massimo , Greco Gabriella , Oliva Fabrizio , Gabrielli Domenico , Gulizia Michele Massimo
Published: April 2022

Background

Several studies have reported that the combination of high TG and low HDL-C, as simplified by the TG/HDL-C ratio, was a predictor of cardiovascular disease independent of LDL-C level. Nevertheless, poor data are available on the predictive role of TG/HDL-C ratio in very high risk (VHR) patients with chronic coronary syndromes (CCS).

Methods

Using the data from the STable Coronary Artery Diseases RegisTry (START) study, an Italian nationwide registry, we assessed the association between the TG/HDL-C ratio and baseline clinical characteristics, pharmacological treatment, and major adverse cardio-cerebrovascular events (MACCE) at 1 year in a large cohort of CCS patients at VHR.

Results

VHR patients with both TG and HDL-C levels available were grouped in tertiles of TG/HDL-C ratio: low (TG/HDL-C ratio <2, n = 967), middle (TG/HDL-C ratio 2–3.3, n = 1,071) and high (TG/HDL-C ratio >3.3, n = 1,028). At 1 year from enrolment, 232 (7.6%) patients presented a MACCE, with a higher incidence in the higher tertile, even though not statistically significant (6.0, 8.2, and 8.4% in the low, middle and high tertile, respectively; p = 0.08). At multivariable analysis, the TG/HDL-C ratio in tertiles did not result an independent predictor of the MACCE (p = 0.29) at 1-year follow-up (HR: 1.30; 95% CI: 0.93–1.82; p = 0.12 middle vs. lower tertile, and HR: 1.22; 95% CI: 0.87–1.72; p = 0.25 higher vs. lower).

Conclusions

In the present large, nationwide cohort of CCS patients at VHR a high TG/HD ratio did not emerge as independent predictor of MACCE at 1 year. Further studies with a longer follow-up are needed to better define the prognostic role of TG/HDL ratio in CCS.
Half a Century of Technological Advances in Pulmonary Drug Delivery: A Personal Perspective
Authors: Clark Andrew R.
Published: April 2022

The last half century of pulmonary product development is reviewed in the context of the main drivers of innovation, technology development, and the advancement of science. A perspective on development timeframes, patent lifetimes, and the odds of success of developing of new inhaler technologies is presented.
Projection of Streamflow Changes Under CMIP6 Scenarios in the Urumqi River Head Watershed, Tianshan Mountain, China
Authors: Yang Min , Li Zhongqin , Anjum Muhammad Naveed , Kayastha Rakesh , Kayastha Rijan Bhakta , Rai Mukesh , Zhang Xin , Xu Chunhai
Published: April 2022

Analyzing climate change impacts on hydrology and future water supply projections is essential for effective water resource management and planning in the large river basins of Asia. In these regions, streamflow and glacier melt remain subject to significant uncertainties due to the lack of confidence in climate change projections and modeling methods. In this study, a glacier dynamics model (the Open Global Glacier Model was coupled with a glacio-hydrological model [the Glacio-hydrological Degree-day Model (GDM)] to predict possible hydrological changes in the head watershed of the Urumqi River under three shared socioeconomic pathways SSP2-4.5, SSP3-7.0, and SSP5-8.5. The GDM was calibrated and validated against in situ observed discharge data for the 2007–2011 and 2012–2018 periods. The resulting Nash–Sutcliffe efficiency (NSE) values were 0.82 and 0.81, respectively. The GDM was driven with an ensemble of five downscaled CMIP6 datasets to examine the potential impacts of climate change on hydrologic processes in the basin. Four runoff components were simulated with the GDM: base flow, rainfall, ice melt, and snow melt. It was determined that rainfall constituted the predominant source of runoff, followed by baseflow and ice melt. During the calibration and validation periods, snow and ice melt contributed 25.14 and 25.62%, respectively, to the total runoff. Under all SSP scenarios, the projected runoff decline indicated that the peak runoff time had passed. It was revealed that a 2°C increase in the monthly average temperature could result in a 37.7% increase in the total discharge of the basin. Moreover, the GDM was more responsive to changes in air temperature than to changes in glacier extent.
Thermodynamic Properties of Fe-Bearing Wadsleyite and Determination of the Olivine-Wadsleyite Phase Transition Boundary in (Mg,Fe)2SiO4 System
Authors: Su Chang , Liu Yonggang , Fan Dawei , Song Wei , Jiang Jiyi , Sun Zhenjun , Yang Guang
Published: April 2022

The self-consistent molar volumes, elastic properties and thermodynamic properties of β-(Mg0.87,Fe0.13)2SiO4wadsleyite have been determined over a wide temperature and pressure range based on an iterative numerical approach and experimental data from the literature. The obtained molar volumes, adiabatic bulk modulus, and shear modulus generally agree with the available experimental and theoretical results. The thermodynamic properties of α-(Mg0.9,Fe0.1)2SiO4were also reinvestigated. Comparisons on thermodynamic properties show that the thermal expansions, heat capacities, and entropies of both β-(Mg0.87,Fe0.13)2SiO4and α-(Mg0.9,Fe0.1)2SiO4exhibit negative and nonlinear behavior with increasing pressure. Besides, the pressure plays a more important role in thermodynamic properties of the α-(Mg0.9,Fe0.1)2SiO4than that of the β-(Mg0.87,Fe0.13)2SiO4. Using the Clausius-Clapeyron equation combined with molar volumes and entropies of both compositions, the phase transition boundary of Fe-bearing olivine and wadsleyite is estimated. The calculated transition pressure shows a nonlinear relationship with increasing temperature, and the value is generally lower than the previous studies on Fe-free olivine and wadsleyite at the same temperature. On the basis of our phase relation, the temperature at the 410 km discontinuity is estimated as 1795 ± 70 K under anhydrous conditions. The results not only confirm the feasibility of the Clausius-Clapeyron equation in obtaining the solid-solid phase transition, but also suggest that the existence of Fe might decrease the transition pressure of olivine-wadsleyite, which would consequently cause a higher temperature at the 410 km discontinuity.
Augmentative and Alternative Communication in the Context of Dramatic Storytelling: A Single-Case Study of a Pre-schooler With a Cochlear Implant
Authors: Wu Jiaojiao , Xie Yuhan
Published: April 2022

This single-case study of a pre-schooler with a cochlear implant aimed to integrate an Augmentative and alternative communication (AAC) intervention with dramatic storytelling activities to improve Jenny’s receptive and expressive language ability and communication skills as a means to address her communication needs. The researcher developed a functional communication image-text vocabulary list of 50 items with five categories: people, social interactions, animals, colors, and frequently used verbs. The intervention was conducted during the regular school day in the corner of a regular classroom 3 days a week for 6 weeks. This study demonstrated that AAC developed during dramatic storytelling activities helped Jenny to improve the effectiveness of functional communication vocabulary learning and increase the frequency of oral language communication. Group dramatic storytelling provides opportunities for learning through peer imitation during naturally occurring activities as well as ones for intentional and systematic AAC instruction during activities.
The Connection of Finns’ Environmental Awareness to Their Anticipatory Competence
Authors: Ratinen Ilkka , Linnanen Lassi
Published: April 2022

Knowledge of people’s abilities must be adapted to a new, sustainable society. Through sustainability competences, the necessary changes in people’s behavior in the pursuit of a sustainable society can be intensified. In this study, Finns (n = 2006) express their knowledge of climate change and biodiversity loss and evaluate their own anticipatory competence. The connection between their environmental awareness and the future’s orientation toward a society of sustainable actions will be studied by statistical analysis. The study discusses how learning sustainability competences can be promoted in science education and reveals the gap between females and males in their objectives for a sustainable future. Finns with higher education have greater environmental awareness than those with lower education. The connection between Finns’ environmental awareness and their structural skills for making a more sustainable future is quite clear.
Schools’ Strengths and Areas for Improvement: Perspectives From External Evaluation Reports
Authors: Seabra Filipa , Henriques Susana , Mouraz Ana , Abelha Marta , Tavares Ana
Published: April 2022

In the context of schools’ growing autonomy, external evaluation mechanisms, including External Evaluation of Schools (EES), are increasingly central to educational policies. This paper is based on the documentary analysis of all reports of the third cycle of EES in Portugal (77 reports), focusing on two of the sections of those reports—the strengths and areas for improvement identified in them. The analysis intends to uncover the areas EES is currently stressing as relevant to assess schools’ quality and identify tendencies across years of implementation and territorial areas (TAs). The results identify some impacts from the TAs, highlighting the effects of the agents interpreting and implementing the policies. Some areas are highlighted as critical—such as the impact of self-evaluation, management, curriculum management, supervision and accompaniment of teaching practices, evaluation, pedagogical practices, or the analysis and improvement of the results. These areas are aligned with broader educational policy priorities.
FGA Controls VEGFA Secretion to Promote Angiogenesis by Activating the VEGFR2-FAK Signalling Pathway
Authors: Li Hui , Cai E. , Cheng Hongyan , Ye Xue , Ma Ruiqiong , Zhu Honglan , Chang Xiaohong
Published: April 2022

Background

Our previous work revealed the high expression of fibrinogen alpha chain (FGA) in patients with endometriosis (EM) and that it could promote the migration and invasion of endometrial stromal cells. Angiogenesis is the key condition for the development of EM. This study was aimed to elucidate the role of FGA in endometrial stromal cells involved in angiogenesis in EM.

Methods

Immunohistochemistry was used to detect the microvessel density (MVD) and VEGF expression in the eutopic endometrium samples from EM and non-EM. The conditioned medium (CM) of human primary eutopic endometrial stromal cells (EuESC) and immortalized endometrial stromal cell line hEM15A with FGA knockdown were collected and used to treat human umbilical vein endothelial cells (HUVECs). Then, tube formation assay, EdU assay, wound assay, transwell assay and flow cytometry assays were performed to assess the function of HUEVCs in vitro. The angiogenic capability of HUVECs was further measured using a matrigel plug assay with BALB/c nude mice in vivo. Immunofluorescence was used to detect the expression of F-actin and VE-cadherin. RT-PCR and western blotting were used to detect the expression of angiogenesis-related factors in endometrial stromal cells and downstream signalling pathways in HUVECs.

Results

MVD and VEGF expression in the eutopic endometrium of EM patients were significantly higher than those in the normal endometrium of non-EM patients, and the increased MVD in EM indicates an increased risk of recurrence. Functionally, we found that CM of endometrial stromal cells with FGA knockdown could inhibit HUEVCs migration and tube formation in vitro and in vivo, while having no significant effect on HUVECs proliferation, apoptosis and cell cycle. Mechanically, the expression of VEGFA, PDGF, FGF-B, VEGF, MMP-2 and MMP-9 was reduced in hEM15A cells with FGA knockdown. CM of hEM15A cells with FGA knockdown reduced the number of microfilaments and pseudopodia, as well as the expression of VE-cadherin, and inhibited the activity of VEGFR2 and the FAK signalling pathway in HUVECs.

Conclusion

Our study demonstrated FGA could enhance the interaction between endometrial stromal cells and HUVECs via the potential VEGA-VEGFR-FAK signalling axis and promote EM angiogenesis, revealing a promising therapeutic approach for EM.
Periprostatic Adipose Tissue Microenvironment: Metabolic and Hormonal Pathways During Prostate Cancer Progression
Authors: Sacca Paula Alejandra , Calvo Juan Carlos
Published: April 2022

The periprostatic adipose tissue (PPAT) is a site of invasion of prostate cancer (PCa) and is part of the microenvironment. It was shown that PPAT secretes factors and fatty acids (FAs) that alter the microenvironment of the PCa. The PPAT secretome of patients with PCa-T3 stage (PPAT-T3) has a metabolic profile enriched in several pathways related to energy production, indicating a greater energy requirement by the tumor, when compared to that of patients in the PCa-T2 stage (PPAT-T2). PPAT-T3 also shows enrichment in pathways related to hormone response, polyamine synthesis, and control of protein synthesis, through amino acid, RNA, and nucleotide metabolism. PPAT-T2 and PPAT-BPH secretomes have less complex metabolic profile, both related with energy balance, while PPAT-BPH has hormone response through insulin pathway. Undoubtedly, a deeper characterization of the human PPAT will lead to a better understanding of the disease and possibly allow new stratification factors and the design of a specific therapy that targets crucial components of the tumor microenvironment as another way to treat or control the disease.
Preclinical Models to Evaluate the Human Response to Autoantigen and Antigen-Specific Immunotherapy in Human Type 1 Diabetes
Authors: Houeiss Pamela , Boitard Christian , Luce Sandrine
Published: April 2022

Type 1 Diabetes (T1D) is an autoimmune disease that results from the destruction of pancreatic islet β-cells by auto-reactive T cells. The clinical management of T1D faces the lack of fully predictive biomarkers in its preclinical stage and of antigen-specific therapies to induce or re-induce immune tolerance to β-cell autoantigens and prevent its development. From a therapeutic standpoint, preclinical models of T1D have fallen short of directly translating into humans. To circumvent this limitation, preclinical models are being optimized to allow defining autoantigen epitopes that are presented to T cells and directly apply to the human. In this review, we propose to make a point on the latest available models such as humanized immunodeficient NOD mice models and HLA and autoantigen transgenic mice and their application in the context of T1D.
Dynamic Performance Evaluation of an Integrated 15 MW Floating Offshore Wind Turbine Under Typhoon and ECD Conditions
Authors: Liu Shiqi , Chuang Zhenju , Qu Yan , Li Xin , Li Chunzheng , He Zhen
Published: April 2022

Technology innovation has led to an increase in floating wind turbine size aimed at releasing the pressure on capital cost and increasing its capacity factor. Large-size turbines pose high challenges regarding design with essential structure reliability. The dynamic performance of an integrated 15-megawatt (MW) wind turbine under extreme sea loads is investigated in this paper. Platform motions, mooring system positioning forces, sizeable blades, and tower behaviors are all studied under the targeted typhoon condition and extreme coherent gust with direction change (ECD) wind condition. Potential flow theory is used to analyze the first-order wave load, mean-drift wave load, and second-order difference-frequency wave load on the substructure of the ultra-large 15 MW floating offshore wind turbine (FOWT). The blade element momentum (BEM) theory is adopted for the calculation of the aerodynamic loads on the floating wind turbine, and the finite element method (FEM) is applied to analyze the mooring lines of the floating wind turbine. The results show that the effect of quadratic transfer function (QTF) will significantly increase the dynamic response of FOWT under the typhoon sea state. The ECD wind condition has an influential impact on the motion responses, the axial force of the mooring lines, and structural responses under the normal operating state.
Characteristics and Hazards of Plug-In Hybrid Electric Vehicle Fires Caused by Lithium-Ion Battery Packs With Thermal Runaway
Authors: Cui Yan , Cong Beihua , Liu Jianghong , Qiu Mingming , Han Xin
Published: April 2022

Fire accidents constitute a significant safety concern for automotive lithium-ion battery packs and have impeded the development of electric vehicles (EVs). While fire safety concerns have been raised about EVs, their fire performance remains unknown, especially for plug-in hybrid electric vehicles (PHEVs). Hence, this paper conducted full-scale fire experiments of PHEVs to explore their fire behavior and characteristics. Two brand new PHEVs were employed, and their power battery packs were ignited as the origin of the fire to simulate the representative fire scenario. Results showed that visible flames appeared around the chassis after about 60 min of the experimental procedure. Around the fire emerged, the battery packs intermittently released plenty of white smoke, which induced gas-phase explosions. The main component of the smoke was combustible gases. The SUV-type PHEV test took 9 min 11 s for the chassis flames to evolve into a passenger compartment fire. Due to the slow propagation of the fire in sedan-type PHEV, it required 9 min 56 s for flames to engulf the rear part of the sedan. The maximum temperature of PHEV fires was 843.6°C, while the maximum height of the fire reached around 3 m. At a distance of 1 m, the radiative heat emitted from burning PHEVs peaked at 1.151 kW/m2. Moreover, some secondary hazards of PHEV fires were illustrated. These results stimulate future experiments seeking novel flame retardant materials for PHEVs and provide helpful guidance on screening reliable PHEV fire prediction and protection strategies.
Technical Characteristics and Development Trend of Printed Circuit Heat Exchanger Applied in Floating Liquefied Natural Gas
Authors: Xie Liyi , Zhuang Dawei , Li Zhiqiang , Ding Guoliang
Published: April 2022

The printed circuit heat exchanger with high efficiency and good compactness and reliability presents potential application in the floating liquefied natural gas platform. This paper offers a review on technical characteristics and development trend of the printed circuit heat exchanger applied in floating liquefied natural gas, including the development state of printed circuit heat exchangers, the application state of printed circuit heat exchangers in floating liquefied natural gas, and the key issues for potential application of printed circuit heat exchangers in floating liquefied natural gas. Firstly, the existing research results of heat transfer and pressure drop characteristics of printed circuit heat exchangers with various flow channels are analyzed, and the correlations of the heat transfer coefficients and the pressure drop of these flow channels are summarized. Then, the application state of printed circuit heat exchangers in floating liquefied natural gas is introduced, and the functions of printed circuit heat exchangers used in the existing floating liquefied natural gas facilities are analyzed. Finally, the key issues for applying printed circuit heat exchangers in floating liquefied natural gas, including the structure design criteria, influence mechanism of sloshing conditions on performance, and methods of suppressing the adverse effects of sloshing conditions, are proposed. It is indicated that the present studies focus on the effect of single sloshing motion on the thermal–hydraulic performances of printed circuit heat exchangers, but few attention has been paid onto the coupling effects of multiple sloshing motions which conform more closely to the actual operation conditions of printed circuit heat exchangers in floating liquefied natural gas. Thus, the future work should aim at the influence mechanisms and structure optimizations in terms of thermal–hydraulic performance under multiple sloshing conditions.
Dust Aerosol Vertical Profiles in the Hinterland of Taklimakan Desert During Summer 2019
Authors: Bi Jianrong , Li Zhengpeng , Zuo Dapeng , Yang Fan , Li Bowen , Ma Junyang , Huang Zhongwei , He Qing
Published: April 2022

Dust aerosol vertical profiles are very essential to accurately evaluate their climate forcing and trans-subcontinental transportation to downstream areas. We initiated a joint comprehensive field experiment to investigate the vertical profiles and optical characteristics of dust aerosol in the hinterland of Taklimakan Desert (TD) during summer 2019. After smoothing the raw signals, the CHM15k ceilometer could distinctly detect a moderate intensity of dust layer, cloud layer, and subsequent rainfall process. The results showed that dust events frequently occurred in TD during the entire period; the overall mean PM2.5, PM10, PM2.5/PM10, and Ångström exponent are 110.4 ± 121.0 μg/m3, 317.2 ± 340.0 μg/m3, 0.35 ± 0.07, and 0.28 ± 0.12, respectively, suggesting that dust particles are predominant aerosol types in TD. There was an obvious summertime dust stagnation layer persistently hanged over the desert at 1.5–3.0-km height. A deep and intense daytime convective structure was also detected by the ceilometer, with maximum aerosol mixing layer height of ∼3 km that appeared at 12:00 UTC, which was in favor of lifting the ground-generated dust particles into the upper atmosphere. The normalized range-corrected signal log10(RCS), aerosol extinction σ(z), and backscattering coefficient β(z) of the ceilometer were higher than 6.2, 0.5 km−1, and 0.01 km−1 sr−1 for heavy dust storms, respectively, and the corresponding vertical optical range was smaller than 1.0 km. The aerosol lidar ratio was equal to 50 sr, which was greatly different from those of clear-sky cases. The retrieved σ(z) values were about 2.0, 0.5, 0.14, and 0.10 km−1 at 200-m height, respectively, under strong dust storm, blowing dust, floating dust, and clear-sky conditions. This indicated that the aerosol extinction coefficients under dust events were about 3–10 times greater than those of clear-sky cases. The statistics of the aerosol optical parameters under different dust intensities in TD were very helpful to explore and validate dust aerosols in the application of climate models or satellite remote sensing.
Temporal Variation of Airborne Dust Concentrations in the Mogao Grottoes, Dunhuang, China
Authors: Zhang Guobin , Tan Lihai , Zhang Weimin , Zhan Hongtao , Qiu Fei
Published: April 2022

Dust storms bring a large quantity of dust aerosols from arid and semi-arid regions of the Earth. However, real-time dust concentration data for dust storms in arid regions, important for wind erosion studies, are still limited. Here, temporal variation of airborne dust concentrations in the Mogao Grottoes, Northwest China, during the monitoring period from February to October 2012 and typical dust storms under different wind directions were analyzed. Results reveal that the monthly mean total suspended particle (TSP), particulate matter less than 10 μm (PM10), and particulate matter less than 2.5 μm (PM2.5) concentrations gradually decreased from February to October. The daily mean dust concentrations fluctuated with the day, with extreme values occurring mainly on February, March, and April. The daily mean PM10/TSP ratio ranged from 0.67 to 0.98 (mean of 0.82), and the PM2.5/PM10 ratio ranged from 0.31 to 0.73 (mean of 0.55), indicating PM10 dominated in TSP. In typical dust storms, the maximum real-time concentrations can reach 16, 000–21, 000 μg TSP m−3, ∼11, 000 μg PM10 m−3, and 3000–3500 μg PM2.5 m−3, and extreme real-time dust concentrations of 50358.03 μg TSP m−3, 33100.86 μg PM10 m−3, and 7502.59 μg PM2.5 m−3 were recorded. Coincidence of the dry climate and windy season and sufficient dust sources in the surrounding environment contributed to the high dust concentrations in the Mogao Grottoes. To achieve the goal of minimizing the damage of falling dust to the murals and statues, establishing a dust storm early warning system and improving the existing sand control system are recommended.
Do Biotic and Abiotic Factors Influence the Prevalence of a Common Parasite of the Invasive Alien Ladybird Harmonia axyridis?
Authors: Haelewaters Danny , Hiller Thomas , Ceryngier Piotr , Eschen René , Gorczak Michał , Houston Makenna L. , Kisło Kamil , Knapp Michal , Landeka Nediljko , Pfliegler Walter P. , Zach Peter , Aime M. Catherine , Nedvěd Oldřich
Published: April 2022

Hesperomyces virescens (Ascomycota, Laboulbeniales), a fungal ectoparasite, is thus far reported on Harmonia axyridis from five continents: North and South America, Europe, Africa, and Asia. While it is known that He. virescens can cause mortality of Ha. axyridis under laboratory conditions, the role of biotic and abiotic factors in influencing the distribution of He. virescens in the field is unknown. We collected and screened 3,568 adult Ha. axyridis from 23 locations in seven countries in Central Europe between October and November 2018 to test the effect of selected host characters and climate and landscape variables on the infection probability with He. virescens. Mean parasite prevalence of He. virescens on Ha. axyridis was 17.9%, ranging among samples from 0 to 46.4%. Host sex, climate, and landscape composition did not have any significant effect on the infection probability of He. virescens on Ha. axyridis. Two color forms, f. conspicua and f. spectabilis, had a significantly lower parasite prevalence compared to the common Ha. axyridis f. novemdecimsignata.
Microscopic Insights Into the Formation of Methanesulfonic Acid–Methylamine–Ammonia Particles Under Acid-Rich Conditions
Authors: Liu Min , Myllys Nanna , Han Yaning , Wang Zhongteng , Chen Liang , Liu Wei , Xu Jing
Published: April 2022

Understanding the microscopic mechanisms of new particle formation under acid-rich conditions is of significance in atmospheric science. Using quantum chemistry calculations, we investigated the microscopic formation mechanism of methanesulfonic acid (MSA)–methylamine (MA)–ammonia (NH3) clusters. We focused on the binary (MSA)2n-(MA)n and ternary (MSA)3n-(MA)n-(NH3)n, (n = 1–4) systems which contain more acid than base molecules. We found that the lowest-energy isomers in each system possess considerable thermodynamic and dynamic stabilities. In studied cluster structures, all bases are protonated, and they form stable ion pairs with MSA, which contribute to the charge transfer and the stability of clusters. MA and NH3 have a synergistic effect on NPF under acid-rich conditions, and the role of NH3 becomes more remarkable as cluster size increases. The excess of MSA molecules does not only enhance the stability of clusters, but provides potential sites for further growth.
A Bidirectional Mendelian Randomization Study of Selenium Levels and Ischemic Stroke
Authors: Fang Hui , Liu Weishi , Zhang Luyang , Pei Lulu , Gao Yuan , Zhao Lu , Zhang Rui , Yang Jing , Song Bo , Xu Yuming
Published: April 2022

Background: Previous observational studies have shown that circulating selenium levels are inversely associated with ischemic stroke (IS). Our aims were to evaluate the causal links between selenium levels and IS, and its subtypes by Mendelian randomization (MR) analysis.

Methods: We used the two-sample Mendelian randomization (MR) method to determine whether the circulating selenium levels are causally associated with the risk of stroke. We extracted the genetic variants (SNPs) associated with blood and toenail selenium levels from a large genome-wide association study (GWAS) meta-analysis. Inverse variance-weighted (IVW) method was used as the determinant of the causal effects of exposures on outcomes.

Results: A total of 4 SNPs (rs921943, rs6859667, rs6586282, and rs1789953) significantly associated with selenium levels were obtained. The results indicated no causal effects of selenium levels on ischemic stroke by MR analysis (OR = 0.968, 95% CI 0.914–1.026, p = 0.269). Meanwhile, there was no evidence of a causal link between circulating selenium levels and subtypes of IS.

Conclusion: The MR study indicated no evidence to support the causal links between genetically predicted selenium levels and IS. Our results also did not support the use of selenium supplementation for IS prevention at the genetic level.
A Regularized Multi-Task Learning Approach for Cell Type Detection in Single-Cell RNA Sequencing Data
Authors: Upadhyay Piu , Ray Sumanta
Published: April 2022

Cell type prediction is one of the most challenging goals in single-cell RNA sequencing (scRNA-seq) data. Existing methods use unsupervised learning to identify signature genes in each cluster, followed by a literature survey to look up those genes for assigning cell types. However, finding potential marker genes in each cluster is cumbersome, which impedes the systematic analysis of single-cell RNA sequencing data. To address this challenge, we proposed a framework based on regularized multi-task learning (RMTL) that enables us to simultaneously learn the subpopulation associated with a particular cell type. Learning the structure of subpopulations is treated as a separate task in the multi-task learner. Regularization is used to modulate the multi-task model (e.g.,W1,W2, …Wt) jointly, according to the specific prior. For validating our model, we trained it with reference data constructed from a single-cell RNA sequencing experiment and applied it to a query dataset. We also predicted completely independent data (the query dataset) from the reference data which are used for training. We have checked the efficacy of the proposed method by comparing it with other state-of-the-art techniques well known for cell type detection. Results revealed that the proposed method performed accurately in detecting the cell type in scRNA-seq data and thus can be utilized as a useful tool in the scRNA-seq pipeline.
Histone Methyltransferase DOT1L as a Promising Epigenetic Target for Treatment of Solid Tumors
Authors: Alexandrova Elena , Salvati Annamaria , Pecoraro Giovanni , Lamberti Jessica , Melone Viola , Sellitto Assunta , Rizzo Francesca , Giurato Giorgio , Tarallo Roberta , Nassa Giovanni , Weisz Alessandro
Published: April 2022

The histone lysine methyltransferase DOT1L (DOT1-like histone lysine methyltransferase) is responsible for the epigenetic regulation of gene expression through specific methylation of lysine79 residue of histone H3 (H3K79) in actively transcribed genes. Its normal activity is crucial for embryonic development and adult tissues functions, whereas its aberrant functioning is known to contribute to leukemogenesis. DOT1L is the only lysine methyltransferase that does not contain a SET domain, which is a feature that allowed the development of selective DOT1L inhibitors that are currently investigated in Phase I clinical trials for cancer treatment. Recently, abnormal expression of this enzyme has been associated with poor survival and increased aggressiveness of several solid tumors. In this review evidences of aberrant DOT1L expression and activity in breast, ovarian, prostate, colon, and other solid tumors, and its relationships with biological and clinical behavior of the disease and response to therapies, are summarized. Current knowledge of the structural basis of DOT1L ability to regulate cell proliferation, invasion, plasticity and stemness, cell cycle progression, cell-to-cell signaling, epithelial-to-mesenchymal transition, and chemoresistance, through cooperation with several molecular partners including noncoding RNAs, is also reviewed. Finally, available options for the treatment of therapeutically challenging solid tumors by targeting DOT1L are discussed.
N7-Methylguanosine-Related lncRNAs: Integrated Analysis Associated With Prognosis and Progression in Clear Cell Renal Cell Carcinoma
Authors: Ming Jie , Wang Chunyang
Published: April 2022

N7-Methylguanosine (m7G) and long non-coding RNAs (lncRNAs) have been widely reported to play an important role in cancer. However, there is little known about the relationship between m7G-related lncRNAs and clear cell renal cell carcinoma (ccRCC). To find new potential biomarkers and construct an m7G-related lncRNA prognostic signature for ccRCC, we retrieved transcriptome data and clinical data from The Cancer Genome Atlas (TCGA), and divided the entire set into train set and test set with the ratio of 1:1 randomly. The m7G-related lncRNAs were identified by Pearson correlation analysis (|coefficients| > 0.4, and p < 0.001). Then we performed the univariate Cox regression and least absolute shrinkage and selection operator (LASSO) Cox regression analysis to construct a 12 m7G-related lncRNA prognostic signature. Next, principal component analysis (PCA), the Kaplan–Meier method, time-dependent receiver operating characteristics (ROC) were made to verify and evaluate the risk signature. A nomogram based on the risk signature and clinical parameters was developed and showed high accuracy and reliability for predicting the overall survival (OS). Functional enrichment analysis (GO, KEGG and GSEA) was used to investigate the potential biological pathways. We also performed the analysis of tumor mutation burden (TMB), immunological analysis including immune scores, immune cell infiltration (ICI), immune function, tumor immune escape (TIE) and immunotherapeutic drug in our study. In conclusion, using the 12 m7G-related lncRNA risk signature as a prognostic indicator may offer us insight into the oncogenesis and treatment response prediction of ccRCC.
The Pan-Cancer Landscape of Crosstalk Between TRP Family and Tumour Microenvironment Relevant to Prognosis and Immunotherapy Response
Authors: Wu Gujie , He Min , Yin Xi , Wang Wenmaio , Zhou Jiabin , Ren Kuan , Chen Xinming , Xue Qun
Published: April 2022

Background

Transient Receptor Potential (TRP) channel is a kind of channel protein widely distributed in peripheral and central nervous system. They can be regulated by natural aromatic substances and serve as a therapeutic target for many diseases. However, the role and function of the TRP family genes in tumours remain unclear.

Methods

Gene alterations (mutation, copy number, methylation), expression, clinical features, and prognostic value of the TRP family genes were evaluated in pan-cancer using data from The Cancer Genome Atlas and Genotype-Tissue Expression databases. TRP score was calculated by the ssGSEA function of the R package “GSVA”. The association of TRP score and the tumour microenvironment (TME), especially the tumour immune microenvironment (TIME), along with immunotherapy response were explored in-depth.

Results

TRP family genes were involved in tumour progression and highly associated with poor prognosis in a variety of cancers. TRP score was positively associated with malignant pathways in pan-cancer, such as IL6–JAK–STAT3 signalling, interferon-gamma response, and inflammatory response. All pathways were closely associated with TIME. Elevated TRP score also correlated with multiple immune-related characteristics of the TIME in pan-cancer. Moreover, the TRP score was a predictive biomarker for immune checkpoint inhibitor (ICI) treatments in patients with tumours.

Conclusions

TRP family genes play a key role in pan-cancer and are closely associated with TME. Patients with high TRP scores have excellent immune-activated TIME and immunotherapy sensitivity. Therefore, the TRP score could be a potential biomarker for patients with tumours treated with ICI.
Bioactive Lipids as Chronic Myeloid Leukemia’s Potential Biomarkers for Disease Progression and Response to Tyrosine Kinase Inhibitors
Authors: de Almeida Felipe Campos , Berzoti-Coelho Maria G. , Toro Diana Mota , Cacemiro Maira da Costa , Bassan Vitor Leonardo , Barretto Gabriel Dessotti , Garibaldi Pedro Manoel Marques , Palma Leonardo Carvalho , de Figueiredo-Pontes Lorena Lobo , Sorgi Carlos Arterio , Faciolli Lucia Helena , Gardinassi Luiz Gustavo , de Castro Fabíola Attié
Published: April 2022

Chronic myelogenous leukemia (CML) is a myeloproliferative neoplasm that expresses the Philadelphia chromosome and constitutively activated Bcr-Abl tyrosine kinase in hematopoietic progenitor cells. Bcr-Abl tyrosine-kinase inhibitors (TKI) do not definitively cure all CML patients. The efficacy of TKI is reduced in CML patients in the blastic phase—the most severe phase of the disease—and resistance to this drug has emerged. There is limited knowledge on the underlying mechanisms of disease progression and resistance to TKI beyond BCR-ABL1, as well as on the impact of TKI treatment and disease progression on the metabolome of CML patients. The present study reports the metabolomic profiles of CML patients at different phases of the disease treated with TKI. The plasma metabolites from CML patients were analyzed using liquid chromatography, mass spectrometry, and bioinformatics. Distinct metabolic patterns were identified for CML patients at different phases of the disease and for those who were resistant to TKI. The lipid metabolism in CML patients at advanced phases and TKI-resistant patients is reprogrammed, as detected by analysis of metabolomic data. CML patients who were responsive and resistant to TKI therapy exhibited distinct enriched pathways. In addition, ceramide levels were higher and sphingomyelin levels were lower in resistant patients compared with control and CML groups. Taken together, the results here reported established metabolic profiles of CML patients who progressed to advanced phases of the disease and failed to respond to TKI therapy as well as patients in remission. In the future, an expanded study on CML metabolomics may provide new potential prognostic markers for disease progression and response to therapy.
Restriction of the Global IgM Repertoire in Antiphospholipid Syndrome
Authors: Pashova Shina , Balabanski Lubomir , Elmadjian Gabriel , Savov Alexey , Stoyanova Elena , Shivarov Velizar , Petrov Peter , Pashov Anastas
Published: April 2022

The typical anti-phospholipid antibodies (APLA) in the anti-phospholipid syndrome (APS) are reactive with the phospholipid-binding protein β2GPI as well as a growing list of other protein targets. The relation of APLA to natural antibodies and the fuzzy set of autoantigens involved provoked us to study the changes in the IgM repertoire in APS. To this end, peptides selected by serum IgM from a 7-residue linear peptide phage display library (PDL) were deep sequenced. The analysis was aided by a novel formal representation of the Igome (the mimotope set reflecting the IgM specificities) in the form of a sequence graph. The study involved women with APLA and habitual abortions (n=24) compared to age-matched clinically healthy pregnant women (n=20). Their pooled Igomes (297 028 mimotope sequences) were compared also to the global public repertoire Igome of pooled donor plasma IgM (n=2 796 484) and a set of 7-mer sequences found in the J regions of human immunoglobulins (n=4 433 252). The pooled Igome was represented as a graph connecting the sequences as similar as the mimotopes of the same monoclonal antibody. The criterion was based on previously published data. In the resulting graph, identifiable clusters of vertices were considered related to the footprints of overlapping antibody cross-reactivities. A subgraph based on the clusters with a significant differential expression of APS patients’ mimotopes contained predominantly specificities underrepresented in APS. The differentially expressed IgM footprints showed also an increased cross-reactivity with immunoglobulin J regions. The specificities underexpressed in APS had a higher correlation with public specificities than those overexpressed. The APS associated specificities were strongly related also to the human peptidome with 1 072 mimotope sequences found in 7 519 human proteins. These regions were characterized by low complexity. Thus, the IgM repertoire of the APS patients was found to be characterized by a significant reduction of certain public specificities found in the healthy controls with targets representing low complexity linear self-epitopes homologous to human antibody J regions.
High Levels of Circulating Monocytic Myeloid-Derived Suppressive-Like Cells Are Associated With the Primary Resistance to Immune Checkpoint Inhibitors in Advanced Non-Small Cell Lung Cancer: An Exploratory Analysis
Authors: Bronte Giuseppe , Petracci Elisabetta , De Matteis Serena , Canale Matteo , Zampiva Ilaria , Priano Ilaria , Cravero Paola , Andrikou Kalliopi , Burgio Marco Angelo , Ulivi Paola , Delmonte Angelo , Crinò Lucio
Published: April 2022

Background

Immunotherapy has become the standard of care for non-small cell lung cancer (NSCLC) patients. Some patients experience primary resistance to immunotherapy. Currently, we lack a marker of resistance to immunotherapy. Myeloid-derived suppressive-like cells (MDSCs) can reduce tumor response rate and survival outcomes.

Methods

This is an exploratory prospective observational study on metastatic NSCLC patients starting immunotherapy. Baseline peripheral blood samples were collected. Monocytic (M)-MDSCs were analyzed by flow cytometry. The main clinical outcomes were tumor response, progression-free survival (PFS), and overall survival (OS). The association between MDSC levels and tumor response was assessed. The association of PFS with OS was investigated using the Kaplan–Meier method and the Cox proportional hazards model.

Results

Twenty-two patients were included. The median M-MDSC value was higher in patients with progressive disease than patients with stable disease or partial response, p = 0.045. The median MDSC value in the overall population was 1.9. We found worse PFS (HR = 2.51; p = 0.046) and OS (HR = 2.68; p = 0.042) in patients with M-MDSC values higher than the median.

Conclusions

In this exploratory analysis, high M-MDSC levels are strongly associated with primary resistance to immunotherapy. If validated in larger studies, MDSC levels in blood samples could help to select NSCLC patients for higher benefit from immunotherapy.