bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Air-Purifying Plants on the Reduction of Volatile Organic Compounds in the Indoor Hot Desert Climate
Authors: Al Qassimi Nahla , Jung Chuloh
Published: January 2022

Due to hot desert weather, residents of the United Arab Emirates (UAE) spend 90% of their time indoors, and the interior environment of the newly built apartments with inappropriate material and ventilation is causing sick building syndrome (SBS), faster than in any other country. NASA studies on indoor air pollutants indicate that the usage of 15–18 air-purifying plants in 18–24 cm diameter containers can clean the air in an average 167.2 m2 house (approximately one plant per 9.2 m2). This study investigates the effect of three different types of air-purifying plants, Pachira aquatica, Ficus benjamina, and Aglaonema commutatum, in reducing volatile organic compounds (VOCs) and formaldehyde (CH2O) in hot desert climate. An experiment is performed in which the CH2O and VOCs concentrations are measured in two laboratory spaces (Room 1 and Room 2). Different volumes (5 and 10% of the laboratory volume) of target plants are installed in Room 1, whereas Room 2 is measured under the same conditions without plants for comparison. The results show that the greater the planting volume (10%), the greater is the reduction effect of each VOCs. In summer in hot desert climate, the initial concentration (800 µg/cm3) of CH2O and VOCs is higher, and the reduction amount is higher (534.5 µg/cm3) as well. The reduction amount of CH2O and toluene (C7H8) is particularly high. In the case of C7H8, the reduction amount (45.9 µg/cm3) is higher in summer with Aglaonema commutatum and Ficus benjamina. It is statistically proven that Ficus benjamina is most effective in reducing CH2O and C7H8 in an indoor space in hot desert climate. The findings of this study can serve as basic data for further improving the indoor air quality using only air-purifying plants in hot desert climate of the United Arab Emirates.
Enabling Production of Algal Biofuels by Techno-Economic Optimization of Co-Product Suites
Authors: Kruger Jacob S. , Wiatrowski Matthew , Davis Ryan E. , Dong Tao , Knoshaug Eric P. , Nagle Nick J. , Laurens Lieve M. L. , Pienkos Philip T.
Published: January 2022

Recent techno-economic analysis (TEA) has underscored that for algal biofuels to be cost competitive with petroleum fuels, co-products are necessary to offset the cost of fuel production. The co-product suite must scale with fuel production while also maximizing value from the non-fuel precursor components. The co-product suite also depends on algal biomass composition, which is highly dynamic and depends on environmental conditions during cultivation. Intentional shifts in composition during cultivation are often associated with reduced biomass productivity, which can increase feedstock production costs for the algae-based biorefinery. The optimal algae-based biorefinery configuration is thus a function of many factors. We have found that comprehensive TEA, which requires the construction of process models with detailed mass and energy balances, along with a complete accounting of capital and operating expenditures for a commercial-scale production facility, provides invaluable insight into the viability of a proposed biorefinery configuration. This insight is reflected in improved viability for one biorefining approach that we have developed over the last 10 years, namely, the Combined Algal Processing (CAP) approach. This approach fractionates algal biomass into carbohydrate-, lipid-, and protein-rich fractions, and tailors upgrading chemistry to the composition of each fraction. In particular, transitioning from valorization of only the lipids to a co-product suite from multiple components of high-carbohydrate algal biomass can reduce the minimum fuel selling price (MFSP) from more than $8/gallon of gasoline equivalent (GGE) to $2.50/GGE. This paper summarizes that progress and discusses several surprising implications in this optimization approach.
A Novel Multiple Risk Score Model for Prediction of Long-Term Ischemic Risk in Patients With Coronary Artery Disease Undergoing Percutaneous Coronary Intervention: Insights From the I-LOVE-IT 2 Trial
Authors: Qiu Miaohan , Li Yi , Na Kun , Qi Zizhao , Ma Sicong , Zhou He , Xu Xiaoming , Li Jing , Xu Kai , Wang Xiaozeng , Han Yaling
Published: January 2022

Backgrounds: A plug-and-play standardized algorithm to identify the ischemic risk in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) could play a valuable step to help a wide spectrum of clinic workers. This study intended to investigate the ability to use the accumulation of multiple clinical routine risk scores to predict long-term ischemic events in patients with CAD undergoing PCI.

Methods: This was a secondary analysis of the I-LOVE-IT 2 (Evaluate Safety and Effectiveness of the Tivoli drug-eluting stent (DES) and the Firebird DES for Treatment of Coronary Revascularization) trial, which was a prospective, multicenter, and randomized study. The Global Registry for Acute Coronary Events (GRACE), baseline Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX), residual SYNTAX, and age, creatinine, and ejection fraction (ACEF) score were calculated in all patients. Risk stratification was based on the number of these four scores that met the established thresholds for the ischemic risk. The primary end point was ischemic events at 48 months, defined as the composite of cardiac death, nonfatal myocardial infarction, stroke, or definite/probable stent thrombosis (ST).

Results: The 48-month ischemic events had a significant trend for higher event rates (from 6.61 to 16.93%) with an incremental number of risk scores presenting the higher ischemic risk from 0 to ≥3 (p trend < 0.001). In addition, the categories were associated with increased risk for all components of ischemic events, including cardiac death (from 1.36 to 3.15%), myocardial infarction (MI) (from 3.31 to 9.84%), stroke (3.31 to 6.10%), definite/probable ST (from 0.58 to 1.97%), and all-cause mortality (from 2.14 to 6.30%) (all p trend < 0.05). The net reclassification index after combined with four risk scores was 12.5% (5.3–20.0%), 9.4% (2.0–16.8%), 12.1% (4.5–19.7%), and 10.7% (3.3–18.1%), which offered statistically significant improvement in the performance, compared with SYNTAX, residual SYNTAX, ACEF, and GRACE score, respectively.

Conclusion: The novel multiple risk score model was significantly associated with the risk of long-term ischemic events in these patients with an increment of scores. A meaningful improvement to predict adverse outcomes when multiple risk scores were applied to risk stratification.
Myocardial PD-L1 Expression in Patients With Ischemic and Non-ischemic Heart Failure
Authors: Kushnareva Ekaterina , Kushnarev Vladimir , Artemyeva Anna , Mitrofanova Lubov , Moiseeva Olga
Published: January 2022

Objective: Immune checkpoints inhibitors are promising and wide-spread agents in anti-cancer therapy. However, despite their efficacy, these agents could cause cardiotoxicity, a rare but life-threatening event. In addition, there are still no well-described predictive factors for the development of immune-related adverse events and information on high risk groups. According to known experimental studies we hypothesized that cardiovascular diseases may increase myocardial PD-L1 expression, which could be an extra target for Checkpoint inhibitors and a potential basis for complications development.

Methods: We studied patterns of myocardial PD-L1 expression in non-cancer-related cardiovascular diseases, particularly ischemic heart disease (n = 12) and dilated cardiomyopathy (n = 7), compared to patients without known cardiovascular diseases (n = 10) using mouse monoclonal anti-PD-L1 antibody (clone 22C3, 1:50, Dako). Correlation between immunohistochemical data and echocardiographic parameters was assessed. Statistical analyses were performed using R Statistical Software—R studio version 1.3.1093.

Results: In the myocardium of cardiac patients, we found membranous, cytoplasmic, and endothelial expression of PD-L1 compared to control group. In samples from patients with a history of myocardial infarction, PD-L1 membrane and endothelial expression was more prominent and frequent, and cytoplasmic and intercalated discs staining was more localized. In contrast, samples from patients with dilated cardiomyopathy displayed very faint endothelial staining, negative membrane staining, and more diffuse PD-L1 expression in the cytoplasm and intercalated discs. In samples from the non-cardiac patients, no convincing PD-L1 expression was observed. Moreover, we discovered a significant negative correlation between PD-L1 expression level and left ventricular ejection fraction and a positive correlation between PD-L1 expression level and left ventricular end-diastolic volume.

Conclusions: The present findings lay the groundwork for future experimental and clinical studies of the role of the PD-1/PD-L1 pathway in cardiovascular diseases. Further studies are required to find patients at potentially high risk of cardiovascular adverse events associated with immune checkpoint inhibitors therapy.
Circular Network of Coregulated Sphingolipids Dictates Chronic Hypoxia Damage in Patients With Tetralogy of Fallot
Authors: Zhou Na , Liu Libao , Zou Rongjun , Zou Minghui , Zhang Mingxia , Cao Fan , Liu Wenhua , Yuan Huili , Huang Guodong , Ma Li , Chen Xinxin
Published: January 2022

Background: Tetralogy of Fallot (TOF) is the most common cyanotic heart disease. However, the association of cardiac metabolic reprogramming changes and underlying molecular mechanisms in TOF-related chronic myocardial hypoxia damage are still unclear.

Methods: In this study, we combined microarray transcriptomics analysis with liquid chromatography tandem-mass spectrometry (LC–MS/MS) spectrum metabolomics analysis to establish the metabolic reprogramming that occurs in response to chronic hypoxia damage. Two Gene Expression Omnibus (GEO) datasets, GSE132176 and GSE141955, were downloaded to analyze the metabolic pathway in TOF. Then, a metabolomics analysis of the clinical samples (right atrial tissue and plasma) was performed. Additionally, an association analysis between differential metabolites and clinical phenotypes was performed. Next, four key genes related to sphingomyelin metabolism were screened and their expression was validated by real-time quantitative PCR (QT-PCR).

Results: The gene set enrichment analysis (GSEA) showed that sphingolipid metabolism was downregulated in TOF and the metabolomics analysis showed that multiple sphingolipids were dysregulated. Additionally, genes related to sphingomyelin metabolism were identified. We found that four core genes, UDP-Glucose Ceramide Glucosyltransferase (UGCG), Sphingosine-1-Phosphate Phosphatase 2 (SGPP2), Fatty Acid 2-Hydroxylase (FA2H), and Sphingosine-1-Phosphate Phosphatase 1 (SGPP1), were downregulated in TOF.

Conclusion: Sphingolipid metabolism was downregulated in TOF; however, the detailed mechanism needs further investigation.
Change in Computed Tomography-Derived Fractional Flow Reserve Across the Lesion Improve the Diagnostic Performance of Functional Coronary Stenosis
Authors: Yan Hankun , Gao Yang , Zhao Na , Geng Wenlei , Hou Zhihui , An Yunqiang , Zhang Jie , Lu Bin
Published: January 2022

Aims: This study sought to evaluate the diagnostic performance of change in computed tomography-derived fractional flow reserve (CT-FFR) across the lesion (ΔCT-FFR) for identifying ischemia lesions with FFR as the reference standard.

Methods: Patients who underwent coronary CT angiography (CCTA) and FFR measurement within 1 week from December 2018 to December 2019 were retrospectively enrolled. CT-FFR within 2 cm distal to the lesion, ΔCT-FFR and plaque characteristics were analyzed. The diagnostic accuracy of CCTA (coronary stenosis ≥ 50%), CT-FFR ≤ 0.80, and ΔCT-FFR ≥ 0.15 (based on the largest Youden index) were assessed with FFR as the reference standard. The relationship between plaque characteristics and ΔCT-FFR was analyzed.

Results: The specificity of ΔCT-FFR and CT-FFR were 70.8 and 67.4%, respectively, which were both higher than CCTA (39.3%) (both P < 0.001), while there were no statistical significance in sensitivity among the three (84.5, 77.4, 88.1%, respectively; P = 0.08). The area under the curves (AUCs) of ΔCT-FFR and CT-FFR were 0.803 and 0.743, respectively, which were both higher than that of CCTA (0.637) (both P < 0.05), and the AUC of ΔCT-FFR was higher than that of CT-FFR (P < 0.001). Multivariable analysis showed that low-attenuation plaque (LAP) volume (odds ratio [OR], 1.006) and plaque length (OR, 1.021) were independently correlated with ΔCT-FFR (both P < 0.05).

Conclusions: CT-FFR and ΔCT-FFR and here especially the ΔCT-FFR could improve the diagnostic performance of ischemia compared with CCTA alone. LAP volume and plaque length were the independent risk factors of ΔCT-FFR.
Chemokine Receptor Activation Enhances Memory B Cell Class Switching Linked to IgE Sensitization to Alpha Gal and Cardiovascular Disease
Authors: Pattarabanjird Tanyaporn , Wilson Jeffrey M. , Erickson Loren D. , Workman Lisa J. , Qiao Hui , Ghosheh Yanal , Gulati Rishab , Durant Chistopher , Vallejo Jenifer , Saigusa Ryosuke , Platts-Mills Thomas A. E. , Taylor Angela M. , Ley Klaus , McNamara Coleen A.
Published: January 2022

Background: Recent studies have suggested that IgE sensitization to α-gal is associated with coronary artery disease (CAD). However, the B cell subtype(s) responsible for production of IgE to α-gal and mechanisms mediating this production remain elusive.

Methods: Single cell multi-omics sequencing, was utilized to phenotype B cells obtained from 60 subjects that had undergone coronary angiography in whom serum IgE was evaluated by ImmunoCAP. Bioinformatics approaches were used to identify B cell subtype(s) and transcriptomic signatures associated with α-gal sensitization. In vitro characterization of chemokine/chemokine receptor pairs on switched memory B cells associated with IgE to α-gal was performed.

Results: Of the 60 patients, 17 (28%) were positive for IgE to α-gal. CITESeq identified CCR6+ class-switched memory (SWM) B cells and CXCR4 expresssion on these CCR6+ SWM B cells as significantly associated with IgE sensitization to α-gal but not to other common allergens (peanut or inhalants). In vitro studies of enriched human B cells revealed significantly greater IgE on SWM B cells with high CCR6 and CXCR4 expression 10 days after cells were treated with IL-4 and CD40 to stimulate class switch recombination. Both CCL20 (CCR6 ligand) and CXCL12 (ligand for CXCR4) increased the expression of IgE on SWM B cells expressing their receptors. However, they appeared to have unique pathways mediating this effect as only CCL20 increased activation-induced cytidine deaminase (AID), while CXCL12 drove proliferation of CXCR4+ SWM B cells. Lastly, correlation analysis indicated an association between CAD severity and the frequency of both CCR6+ SWM and CXCR4+ SWM B cells.

Conclusions: CCR6+ SWM B cells were identified as potential producers of IgE to α-gal in CAD patients. Additionally, our findings highlighted non-chemotaxis roles of CCL20/CCR6 and CXCL12/CXCR4 signaling in mediating IgE class switching and cell proliferation of SWM B cells respectively. Results may have important implications for a better understanding and better therapeutic approaches for subjects with IgE sensitization to α-gal.
Relation Between Coronary Tortuosity and Vasomotor Dysfunction in Patients Without Obstructed Coronaries?
Authors: Jansen Tijn P. J. , van Keeken Kyra , Konst Regina E. , Dimitriu-Leen Aukelien , Maas Angela H. E. M. , van Royen Niels , Damman Peter , Elias-Smale Suzette
Published: January 2022

Background: A large proportion of patients with angina and no obstructive coronary artery disease (ANOCA) has underlying coronary vasomotor dysfunction (CVDys), which can be diagnosed by a coronary function test (CFT). Coronary tortuosity is a common angiographic finding during the CFT. Yet, no data exist on the association between vasomotor dysfunction and coronary tortuosity.

Aim: To investigate the association between CVDys and coronary tortuosity in patients with ANOCA

Methods: All consecutive ANOCA patients who underwent clinically indicated CFT between February 2019 and November 2020 were included. CFT included acetylcholine spasm testing to diagnose epicardial or microvascular spasm, and adenosine testing to diagnose microvascular dysfunction (MVD). MVD was defined as an index of microvascular resistance (IMR) ≥ 25 and/or coronary flow reserve (CFR) <2.0. Coronary tortuosity, was scored (no, mild, moderate or severe) based on the angles of the curvatures in the left anterior descending (LAD) artery on angiography.

Results: In total, 228 patients were included (86% female, mean age 56 ± 9 years). We found coronary artery spasm in 81% of patients and MVD in 45% of patients (15%: abnormal CFR, 30%: abnormal IMR). There were 73 patients with no tortuosity, 114 with mild tortuosity, 41 with moderate tortuosity, and no patients with severe tortuosity. No differences were found in cardiovascular risk factors or medical history, and the prevalence of CVDys did not differ between the no tortuosity, mild tortuosity and moderate tortuosity group (82, 82, and 85%, respectively).

Conclusion: In this study, CVDys was not associated with coronary tortuosity. Future experimental and clinical studies on the complex interplay between coronary tortuosity, wall shear stress, endothelial dysfunction and coronary flow are warranted.
A Preclinical Rat Model of Heart Failure With Preserved Ejection Fraction With Multiple Comorbidities
Authors: Hubesch Géraldine , Hanthazi Aliénor , Acheampong Angela , Chomette Laura , Lasolle Hélène , Hupkens Emeline , Jespers Pascale , Vegh Grégory , Wembonyama Cécile Watu Malu , Verhoeven Caroline , Dewachter Céline , Vachiery Jean-Luc , Entee Kathleen Mc , Dewachter Laurence
Published: January 2022

Heart failure with preserved ejection fraction (HFpEF) is a common complex clinical syndrome for which there are currently few evidence-based therapies. As patients with HFpEF very often present with comorbidities comprising the metabolic syndrome, we hypothesized, that metabolic syndrome could lead over time to the development of diastolic dysfunction and HFpEF. Obesity-prone rats were exposed to high-fat diet and compared to obesity-resistant rats fed with standard chow. Phenotyping of metabolic syndrome, associated with echocardiographic and cardiac hemodynamic measurements, was performed after 4 and 12 months. Blood and myocardial tissue sampling were performed for pathobiological evaluation. High-fat diet in obesity-prone rats elicited metabolic syndrome, characterized by increased body and abdominal fat weights, glucose intolerance and hyperlipidemia, as well as increased left ventricular (LV) systolic pressure (after 12 months). This was associated with LV diastolic dysfunction (assessed by increased LV end-diastolic pressure) and pulmonary hypertension (assessed by increased right ventricular systolic pressure). Echocardiography revealed significant concentric LV hypertrophy, while LV ejection fraction was preserved. LV remodeling was associated with cardiomyocyte hypertrophy, as well as myocardial and perivascular fibrosis. Circulating levels of soluble ST2 (the interleukin-1 receptor-like) markedly increased in rats with HFpEF, while plasma NT-proBNP levels decreased. RNA-sequencing analysis identified clusters of genes implicated in fatty acid metabolism and calcium-dependent contraction as upregulated pathways in the myocardium of rats with HFpEF. High-fat diet during 12 months in obesity-prone rats led to the development of a relevant preclinical model of HFpEF with multiple comorbidities, suitable for investigating novel therapeutic interventions.
Baseline Low-Density-Lipoprotein Cholesterol Modifies the Risk of All-Cause Death Associated With Elevated Lipoprotein(a) in Coronary Artery Disease Patients
Authors: Yao Younan , Liu Jin , Wang Bo , Zhou Ziyou , Lu Xiaozhao , Huang Zhidong , Deng Jingru , Yang Yongquan , Tan Ning , Chen Shiqun , Chen Jiyan , Liu Yong
Published: January 2022

Background: The prognostic value of elevated lipoprotein(a) [Lp(a)] in coronary artery disease (CAD) patients is inconsistent in previous studies, and whether such value changes at different low-density-lipoprotein cholesterol (LDL-C) levels is unclear.

Methods and Findings: CAD patients treated with statin therapy from January 2007 to December 2018 in the Guangdong Provincial People's Hospital (NCT04407936) were consecutively enrolled. Individuals were categorized according to the baseline LDL-C at cut-off of 70 and 100 mg/dL. The primary outcome was 5-year all-cause death. Multivariate Cox proportional models and penalized spline analyses were used to evaluate the association between Lp(a) and all-cause mortality. Among 30,908 patients, the mean age was 63.1 ± 10.7 years, and 76.7% were men. A total of 2,383 (7.7%) patients died at 5-year follow-up. Compared with Lp(a) <50 mg/dL, Lp(a) ≥ 50 mg/dL predicted higher all-cause mortality (multivariable adjusted HR = 1.19, 95% CI 1.07–1.31) in the total cohort. However, when analyzed within each LDL-C category, there was no significant association between Lp(a) ≥ 50 mg/dL and higher all-cause mortality unless the baseline LDL-C was ≥ 100 mg/dL (HR = 1.19, 95% CI 1.04–1.36). The results from penalized spline analyses were robust.

Conclusions: In statin-treated CAD patients, elevated Lp(a) was associated with increased risks of all-cause death, and such an association was modified by the baseline LDL-C levels. Patients with Lp(a) ≥ 50 mg/dL had higher long-term risks of all-cause death compared with those with Lp(a) <50 mg/dL only when their baseline LDL-C was ≥ 100 mg/dL.
Microscopic Mechanism Angle of Repose in Friable Loess and Its Relationship With Slope Angle
Authors: Dong Haoyu , Wang Jiading , Zhang Dengfei , Xu Yuanjun , Li Zhenxiao
Published: January 2022

The angle of repose in soil particles plays a key role in slope stability. There was a need for the investigation on the association between the angle of repose in loess particles and the angle of slopes. The fixed funnel methods with different particle sizes were carried out. The pressure of particle gravity weight was obtained based on the vibration stacking test. Four contact structures in loess particles were put forward including the triangular pyramid contact structure (TS), rectangular pyramid contact structure (RS), pentagonal pyramid contact structure (PS), and hexagon contact structure (HS). The particles transformed successively in four kinds of contact structures. The transformation of entropy value of the particles in different accumulation areas was discussed during the process of accumulation. The relationship between the natural angle of repose and the evolution of the contact structures was established. Combined with the existing experimental conclusion that loess particles transform in four stable states, in turn, the reason that the friction angle of uniform sand particles proposed by Shields in 1936 is 33° was explained. The formation theory of the loess angle of repose was well extended to speculate the formation process of the loess slope system. It is verified that loess slopes were mainly distributed under 30°.
Cooperative Learning With and About Internet Forums: A Case Study on a Unit on the Consumption and Chemistry of Mineral Water vs. Tap Water
Authors: Dittmar Johanna , Eilks Ingo
Published: January 2022

In today’s society, digital media play an increasing role in gathering and exchanging information. A growing part of communication takes place in the Internet and many people are increasingly influenced by information provided via digital and social media. Development of critical media literacy is needed, if the general public is expected to effectively deal with this flood of information and to become able to distinguish between correct and false information sources. Thus, critical media education becomes an important aim of education in general, and of chemistry education in particular when considering questions directly related to chemistry and its associated consumer products or technologies. The article describes a curriculum development case study investigating the integration of media education with chemistry learning along the case of learning with and about Internet forums on the topic of water chemistry. A unit integrating theoretical and practical chemistry learning based on student communication is described, which is built around a digital forum operated by Moodle. The unit design and findings from the implementation are presented.
Maternal Pre-Pregnancy Obesity Combined With Abnormal Glucose Metabolism Further Increases Adverse Pregnancy Outcomes in Chinese Pregnant Women
Authors: Li Mei-Fang , Ke Jiang-Feng , Ma Li , Wang Jun-Wei , Zhang Zhi-Hui , Li Jing-Bo , Li Lian-Xi
Published: January 2022

Aims

Our aim was to evaluate the separate and combined effects of maternal pre-pregnancy obesity and gestational abnormal glucose metabolism (GAGM) on adverse perinatal outcomes.

Methods

A total of 2,796 Chinese pregnant women with singleton delivery were studied, including 257 women with pre-pregnancy obesity alone, 604 with GAGM alone, 190 with both two conditions, and 1,745 with neither pre-pregnancy obesity nor GAGM as control group. The prevalence and risks of adverse pregnancy outcomes were compared among the four groups.

Results

Compared with the normal group, pregnant women with maternal pre-pregnancy obesity alone, GAGM alone, and both two conditions faced significantly increased risks of pregnancy-induced hypertension (PIH) (odds ratio (OR) 4.045, [95% confidence interval (CI) 2.286–7.156]; 1.993 [1.171–3.393]; 8.495 [4.982–14.485]), preeclampsia (2.649 [1.224–5.735]; 2.129 [1.128–4.017]; 4.643 [2.217–9.727]), cesarean delivery (1.589 [1.212–2.083]; 1.328 [1.095–1.611]; 2.627 [1.908–3.617]), preterm delivery (1.899 [1.205–2.993]; 1.358 [0.937–1.968]; 2.301 [1.423–3.720]), macrosomia (2.449 [1.517–3.954]; 1.966 [1.356–2.851]; 4.576 [2.895–7.233]), and total adverse maternal outcomes (1.762 [1.331–2.332]; 1.365 [1.122–1.659]; 3.228 [2.272–4.587]) and neonatal outcomes (1.951 [1.361–2.798]; 1.547 [1.170–2.046]; 3.557 [2.471–5.122]). Most importantly, there were no obvious risk differences in adverse pregnancy outcomes between maternal pre-pregnancy obesity and GAGM group except PIH, but pregnant women with both obesity and GAGM exhibited dramatically higher risks of adverse pregnancy outcomes than those with each condition alone.

Conclusions

Maternal pre-pregnancy obesity and GAGM were independently associated with increased risks of adverse pregnancy outcomes. The combination of pre-pregnancy obesity and GAGM further worsens adverse pregnancy outcomes compared with each condition alone.
Gonadotropin Inhibitory Hormone and Its Receptor: Potential Key to the Integration and Coordination of Metabolic Status and Reproduction
Authors: Bédécarrats Grégoy Y. , Hanlon Charlene , Tsutsui Kazuyoshi
Published: January 2022

Since its discovery as a novel gonadotropin inhibitory peptide in 2000, the central and peripheral roles played by gonadotropin-inhibiting hormone (GnIH) have been significantly expanded. This is highlighted by the wide distribution of its receptor (GnIH-R) within the brain and throughout multiple peripheral organs and tissues. Furthermore, as GnIH is part of the wider RF-amide peptides family, many orthologues have been characterized across vertebrate species, and due to the promiscuity between ligands and receptors within this family, confusion over the nomenclature and function has arisen. In this review, we intend to first clarify the nomenclature, prevalence, and distribution of the GnIH-Rs, and by reviewing specific localization and ligand availability, we propose an integrative role for GnIH in the coordination of reproductive and metabolic processes. Specifically, we propose that GnIH participates in the central regulation of feed intake while modulating the impact of thyroid hormones and the stress axis to allow active reproduction to proceed depending on the availability of resources. Furthermore, beyond the central nervous system, we also propose a peripheral role for GnIH in the control of glucose and lipid metabolism at the level of the liver, pancreas, and adipose tissue. Taken together, evidence from the literature strongly suggests that, in fact, the inhibitory effect of GnIH on the reproductive axis is based on the integration of environmental cues and internal metabolic status.
LINC00467 Is Upregulated by DNA Copy Number Amplification and Hypomethylation and Shows ceRNA Potential in Lung Adenocarcinoma
Authors: Wang Wen , Bo Hao , Liang Yumei , Li Guoli
Published: January 2022

Lung adenocarcinoma (LUAD) is the most common histological lung cancer, and it is the leading cause of cancer-related deaths worldwide. Long noncoding RNAs (lncRNAs) have been implicated in tumorigenesis. LINC00467 is a novel lncRNA that is abnormally expressed in several cancer types including LUAD. However, its function and regulatory mechanism in LUAD progression remain unclear. In this study, based on The Cancer Genome Atlas data mining, we demonstrated that DNA copy number amplification and hypomethylation was positively correlated with LINC00467 expression in LUAD. In addition, DNA copy number amplification was significantly associated with distant metastasis, immune infiltration and poor survival. Microarray analysis demonstrated that LINC00467 knockdown in the LUAD A549 cell line led to a distinct microRNA expression profile that impacted various target genes involved in multiple biological processes. This finding suggests that LINC00467 may regulate LUAD progression by functioning as a competing endogenous RNA (ceRNA). Finally, we constructed a ceRNA network that included two microRNAs (hsa-miR-1225-5p, hsa-miR-575) and five mRNAs (BARX2, BCL9, KCNK1, KIAA1324, TMEM182) specific to LINC00467 in LUAD. Subsequent Kaplan-Meier survival analysis in both The Cancer Genome Atlas and Gene Expression Omnibus databases revealed that two genes, BARX2 and BCL9, were potential prognostic biomarkers for LUAD patients. In conclusion, our data provide possible mechanisms underlying the abnormal upregulation of LINC00467 as well as a comprehensive view of the LINC00467-mediated ceRNA network in LUAD, thereby highlighting its potential role in diagnosis and therapy.
Analysis and Validation of Hub Genes in Blood Monocytes of Postmenopausal Osteoporosis Patients
Authors: Deng Yi-Xuan , He Wen-Ge , Cai Hai-Jun , Jiang Jin-Hai , Yang Yuan-Yuan , Dan Yan-Rong , Luo Hong-Hong , Du Yu , Chen Liang , He Bai-Cheng
Published: January 2022

Osteoporosis is a common systemic bone disease caused by the imbalance between osteogenic activity and osteoclastic activity. Aged women are at higher risk of osteoporosis, partly because of estrogen deficiency. However, the underlying mechanism of how estrogen deficiency affects osteoclast activity has not yet been well elucidated. In this study, GSE2208 and GSE56815 datasets were downloaded from GEO database with 25 PreH BMD women and 25 PostL BMD women in total. The RRA algorithm determined 38 downregulated DEGs and 30 upregulated DEGs. Through GO analysis, we found that downregulated DEGs were mainly enriched in myeloid cell differentiation, cytokine-related functions while upregulated DEGs enriched in immune-related biological processes; pathways like Notch signaling and MAPK activation were found in KEGG/Rectome pathway database; a PPI network which contains 66 nodes and 91 edges was constructed and three Modules were obtained by Mcode; Correlation analysis helped us to find highly correlated genes in each module. Moreover, three hub genes FOS, PTPN6, and CTSD were captured by Cytohubba. Finally, the hub genes were further confirmed in blood monocytes of ovariectomy (OVX) rats by real-time PCR assay. In conclusion, the integrative bioinformatics analysis and real-time PCR analysis were utilized to offer fresh light into the role of monocytes in premenopausal osteoporosis and identified FOS, PTPN6, and CTSD as potential biomarkers for postmenopausal osteoporosis.
CO2 Emissions and The Transport Sector in Malaysia
Authors: Solaymani Saeed
Published: January 2022

Transport is an essential infrastructure for development. With its high share of gross domestic product (GDP), it makes a significant contribution to total CO2 emissions in Malaysia. It is therefore important to pay greater attention to reducing CO2 emissions and sustainable development in this sector. Therefore, this study aims at estimating the relationship between transport CO2 emissions and its key drivers using the Autoregressive Distributed Lag (ARDL) technique. The time period covered by the study extends from 1978 to 2018. It further investigates the response of CO2 emissions to shocks in the value of other variables by employing the generalized impulse response approach. The results suggest that urbanization is the major contributor to the increase in CO2 emissions followed by the carbon intensity of energy in the long-run. Carbon intensity of energy, GDP per transport worker and urbanization contribute significantly to increases in transport CO2 emissions in the short- and long-run. Testing the Environmental Kuznets Curve (EKC) hypothesis recommends that Malaysia continue to be on track to reach the highest level of income and welfare to give pay more attention to the environment. Therefore, the country maintains its CO2 emissions level in the future because of economic development. Therefore, these findings show that energy and environmental policymakers need to pay more attention to improving energy efficiency and the use of low-carbon technologies and electrification in the transport sector and the use of high-quality public transport, particularly in urban areas, for sustainable urban development.
Preferential Begging Responses of Shiny Cowbirds to the Conspecific Chatter Call
Authors: Crudele Ignacio , Reboreda Juan C. , Fiorini Vanina D.
Published: January 2022

Avian brood parasites lay their eggs into the nests of other species, which incubate them and raise the chicks until their independence. Despite living their early weeks of life surrounded by heterospecifics, young brood parasites have the ability to recognize and associate to conspecifics after independence. It has been proposed that the initial conspecific recognition develops when a young parasite encounters a unique species-specific signal that triggers the learning of other aspects of the producer of the signal. For cowbirds (Molothrus spp.), this species-specific signal is hypothesized to be the chatter call. Young birds also could express auditory biases, which in some cases lead to discrimination in favor of conspecific songs. Therefore, the perceptual selectivity for chatters might be also present in nestlings. Our aim was to assess if nestlings of the shiny cowbird (M. bonariensis) present a preferential begging response to conspecific chatter calls. We evaluated if they respond more to the parasitic vocalization than host chicks and if they respond more to the chatter than to heterospecific nonhost calls. We tested shiny cowbird chicks reared by chalk-browed mockingbirds (Mimus saturninus) or house wrens (Troglodytes aedon) and host chicks, as control species. We randomly presented to 6-day-old chicks the following playback treatments: (1) conspecific chatter calls, (2) host calls, used as positive controls, and (3) nonhost calls, used as negative control. We measured if chicks begged during the playback treatments and the begging intensity. When responding to the playback of chatter calls, shiny cowbird chicks begged at a higher frequency and more intensively than host chicks. Shiny cowbird chicks reared by mockingbirds begged more intensively to playbacks of conspecific chatter calls than to host calls, while those reared by wrens begged with a similar intensity to playbacks of conspecific chatter and host calls. On the contrary, wren nestlings begged more intensively to playbacks of the wren call than to chatter calls. Mockingbird nestlings did not beg during any treatment. None of the three species begged during the playback of nonhost calls. Our results show that the chatter call produced a preferential begging response in cowbird nestlings, which may be the beginning of a process of conspecific recognition.
The Downregulation of PTGS2 Mediated by ncRNAs is Tightly Correlated with Systemic Sclerosis-Interstitial Lung Disease
Authors: Xu Zhixiao , Chen Chengshui
Published: January 2022

Background: Interstitial lung disease in systemic sclerosis (SSc-ILD) is one of the most severe complications of systemic sclerosis (SSc) and is the main cause of mortality. In this study, we aimed to explore the key genes in SSc-ILD and analyze the relationship between key genes and immune cell infiltration as well as the key genes relevant to the hallmarks of cancer.

Methods: Weighted gene co-expression network analysis (WGCNA) algorithm was implemented to explore hub genes in SSc-ILD samples from the Gene Expression Omnibus (GEO) database. Logistic regression analysis was performed to screen and verify the key gene related to SSc-ILD. CIBERSORT algorithms were utilized to analyze immune cell infiltration. Moreover, the correlation between the key genes and genes relevant to cancer was also evaluated. Furthermore, non-coding RNAs (ncRNAs) linking to PTGS2 were also explored.

Results: In this study, we first performed WGCNA analysis for three GEO databases to find the potential hub genes in SSc-ILD. Subsequently, we determined PTGS2 was the key gene in SSC-ILD. Furthermore, in CIBERSORT analyses, PTGS2 were tightly correlated with immune cells such as regulatory T cells (Tregs) and was negatively correlated with CD20 expression. Moreover, PTGS2 was associated with tumor growth. Then, MALAT1, NEAT1, NORAD, XIST identified might be the most potential upstream lncRNAs, and LIMS1 and RANBP2 might be the two most potential upstream circRNAs.

Conclusion: Collectively, our findings elucidated that ncRNAs-mediated downregulation of PTGS2, as a key gene in SSc-ILD, was positively related to the occurrence of SSc-ILD and abnormal immunocyte infiltration. It could be a promising factor for SSc-ILD progression to malignancy.
NFAM1 Promotes Pro-Inflammatory Cytokine Production in Mouse and Human Monocytes
Authors: Juchem Kathryn W. , Gounder Anshu P. , Gao Jian Ping , Seccareccia Elise , Yeddula Narayana , Huffmaster Nicholas J. , Côté-Martin Alexandra , Fogal Steven E. , Souza Donald , Wang Sarah Sirui , Glynn Elizabeth R. A. , Yung Ivy , Ritchie Julie , Li Li , Zheng Jie , Mbow M. Lamine , Li Jun , Chanda Sumit K.
Published: January 2022

NFAT activating protein with ITAM motif 1 (NFAM1) is an ITAM bearing-transmembrane receptor that has been reported to play a role in B cell signaling and development. We performed expression analysis of NFAM1 using publicly available gene expression data sets and found that NFAM1 expression is significantly induced in intestinal biopsies from Crohn’s disease (CD) and ulcerative colitis (UC) patients. At the cellular level, we further observed high expression of NFAM1 in monocytes and neutrophils, and low expression in B and T cells. To explore the role of NFAM1 in multiple immune cells and its potential role in IBD, we generated NFAM1-/- mice. In contrast with previous reports using NFAM1-transgenic mice, NFAM1-/- mice have no obvious defects in immune cell development, or B cell responses. Interestingly, NFAM1-/- monocytes produce reduced levels of TNF-α in response to activation by multiple IBD-relevant stimuli, including CD40L, TLR ligands and MDP. Additional cytokines and chemokines such as IL-6, IL-12, CCL3 and CCL4 are also reduced in CD40L stimulated NFAM1-/- monocytes. Collectively, these findings indicate that NFAM1 promotes monocyte activation, thereby amplifying the response to diverse stimuli. Similarly, we observed that deletion of NFAM1 in human monocytes reduces expression of CD40L-induced CCL4. Lastly, to assess the role of NFAM1 in IBD, we compared development of anti-CD40 induced colitis in NFAM1+/+ and NFAM1-/- mice. We found that although NFAM1 deletion had no impact on development of gut pathology, we did observe a decrease in serum TNF-α, confirming that NFAM1 promotes pro-inflammatory cytokine production in vivo. Taken together, we conclude that NFAM1 functions to amplify cytokine production and should be further evaluated as a therapeutic target for treatment of autoimmune disease.
Anti-CD40 Antibody Fused to CD40 Ligand Is a Superagonist Platform for Adjuvant Intrinsic DC-Targeting Vaccines
Authors: Ceglia Valentina , Zurawski Sandra , Montes Monica , Kroll Mitchell , Bouteau Aurélie , Wang Zhiqing , Ellis Jerome , Igyártó Botond Z. , Lévy Yves , Zurawski Gerard
Published: January 2022

CD40 is a potent activating receptor expressed on antigen-presenting cells (APCs) of the immune system. CD40 regulates many aspects of B and T cell immunityviainteraction with CD40L expressed on activated T cells. Targeting antigens to CD40viaagonistic anti-CD40 antibody fusions promotes both humoral and cellular immunity, but current anti-CD40 antibody-antigen vaccine prototypes require co-adjuvant administration for significant in vivo efficacy. This may be a consequence of dulling of anti-CD40 agonist activityviaantigen fusion. We previously demonstrated that direct fusion of CD40L to anti-CD40 antibodies confers superagonist properties. Here we show that anti-CD40-CD40L-antigen fusion constructs retain strong agonist activity, particularly for activation of dendritic cells (DCs). Therefore, we tested anti-CD40-CD40L antibody fused to antigens for eliciting immune responses in vitro and in vivo. In PBMC cultures from HIV-1-infected donors, anti-CD40-CD40L fused to HIV-1 antigens preferentially expanded HIV-1-specific CD8+ T cellsversusCD4+ T cells compared to analogous anti-CD40-antigen constructs. In normal donors, anti-CD40-CD40L-mediated delivery of Influenza M1 protein elicited M1-specific T cell expansion at lower doses compared to anti-CD40-mediated delivery. Also, on human myeloid-derived dendritic cells, anti-CD40-CD40L-melanoma gp100 peptide induced more sustained Class I antigen presentation compared to anti-CD40-gp100 peptide. In human CD40 transgenic mice, anti-CD40-CD40L-HIV-1 gp140 administered without adjuvant elicited superior antibody responses compared to anti-CD40-gp140 antigen without fused CD40L. In human CD40 mice, compared to the anti-CD40 vehicle, anti-CD40-CD40L delivery of Eα 52-68 peptide elicited proliferating of TCR I-Eα 52-68 CD4+ T cells producing cytokine IFNγ. Also, compared to controls, only anti-CD40-CD40L-Cyclin D1 vaccination of human CD40 mice reduced implanted EO771.LMB breast tumor cell growth. These data demonstrate that human CD40-CD40L antibody fused to antigens maintains highly agonistic activity and generates immune responses distinct from existing low agonist anti-CD40 targeting formats. These advantages were in vitro skewing responses towards CD8+ T cells, increased efficacy at low doses, and longevity of MHC Class I peptide display; and in mouse models, a more robust humoral response, more activated CD4+ T cells, and control of tumor growth. Thus, the anti-CD40-CD40L format offers an alternate DC-targeting platform with unique properties, including intrinsic adjuvant activity.
Lidocaine and Bupivacaine Downregulate MYB and DANCR lncRNA by Upregulating miR-187-5p in MCF-7 Cells
Authors: Lin Chiao-Yi , Tseng Wen-Ting , Chang Yao-Yin , Tsai Mong-Hsun , Chuang Eric Y. , Lu Tzu-Pin , Lai Liang-Chuan
Published: January 2022

Background: Breast cancer is the most common malignancy and a leading cause of death among women. The majority of patients require surgery, and retrospective studies have revealed an association between anaesthetic techniques during surgery and clinical outcomes. Local anaesthetics (LAs) influence carcinogenesis by interacting with non-coding RNAs (ncRNAs). However, the detailed mechanisms underlying the association between LAs and ncRNAs remain unclear.

Methods: In this study, the effects of two commonly used LAs, lidocaine and bupivacaine, on the malignancy of MCF-7 breast cancer cells were investigated. The expression profiles of the microRNAs (miRNAs) that responded to treatment with LAs were determined through next-generation sequencing.

Results: Data from the functional assay revealed that the LAs suppressed the proliferation of MCF-7 cells. The result of next-generation sequencing revealed that 131 miRNAs were upregulated, following treatment with the LAs. Validation using polymerase chain reaction (PCR) identified miR-187-5p as a potential biomarker, and it was selected for further analyses. Prediction with bioinformatics tools and luciferase reporter assays revealed that MYB is a direct target gene of miR-187-5p. Based on the hypothesis that lncRNAs acts as miRNA sponges, the target lncRNA, DANCR, of miR-187-5p was predicted using DIANA-LncBase v2 and validated using luciferase reporter assays. In addition, the reciprocal suppressive effect between DANCR and miR-187-5p was determined.

Conclusions: This study suggests that one of the anti-tumour mechanisms of lidocaine and bupivacaine is mediated through the DANCR-miR-187-5p-MYB axis. This may provide a novel molecular mechanism of tumour suppression in breast cancer.
Global Status of Bufavirus, Cosavirus, and Saffold Virus in Gastroenteritis: A Systematic Review and Meta-Analysis
Authors: Razizadeh Mohammad Hossein , Khatami Alireza , Zarei Mohammad
Published: January 2022

Background: Bufavirus (BuV), Human Cosavirus (HCoSV), and Saffold (SAFV) virus are three newly discovered viruses and have been suggested as possible causes of gastroenteritis (GE) in some studies. The aim of the present study was to estimate the overall prevalence of viruses and their association with GE.

Methods: A comprehensive systematic search was conducted in Scopus, Web of Science, PubMed, and Google scholar between 2007 and 2021 to find studies on the prevalence of BuV, HCoSV, and SAFV viruses.

Result: Meta-analysis of the 46 included studies showed the low prevalence of BuV (1.%, 95% CI 0.6–1.5%), HCoSV (0.8%, 95% CI 0.4–1.5%), and SAFV (1.9%, 95% CI 1.1–3.1%) worldwide. Also, no significant association between these viruses and GE was observed. BuV was isolated from patients with GE in Africa, while SAFV was more common in Europe. BuV1 and BuV2 have the same prevalence between the three identified genotypes of BuV. HCoSV-C was the most prevalent genotype of HCoSV, and SAFV2 was the commonest genotype of SAFV. All of these viruses were more prevalent in children older than 5 years of age.

Conclusion: This was the first meta-analysis on the prevalence and association of BuV, HCoSV, and SAFV with GE. While no significant association was found between infection with these viruses and GE, we suggest more studies, especially with case-control design and from different geographical regions in order to enhance our knowledge of these viruses.