bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex-specific associations between phenotypes and environmental exposures
Authors: Zarzar Tomás González , Palmiero Nicole , Kim Dokyoon , Shen Li , Hall Molly 
Published: October 2023

Abstract
Sex and gender differences are ubiquitous in health and disease. We used data from the National Health and Nutrition Examination Survey to identify associations between environmental exposures and health-related phenotypes that differ between males and females. We found a total of 119 sex-specific exposure-phenotype associations, which included phenotypes such as albumin, homocysteine, bilirubin, and hemoglobin levels and exposures to cadmium, lead, benzene, toluene, ethylbenzene, and xylene. Smoking-related exposures were among the exposures with the greatest number of sex-specific phenotypic associations. The positive effects of smoking-related exposure on homocysteine and hemoglobin levels, hematocrit, and red blood cell counts were larger in females than in males. Conversely, the negative effects of smoking-related exposures on albumin and bilirubin levels were larger in males than in females. Our results show potential mechanisms by which women who smoke are at higher risk of cardiovascular diseases, and men have a heightened inflammatory response.
Factors associated with health-related quality of life in women with systemic lupus erythematosus and permanent skin damage – a cross-sectional study
Authors: Oliveira Fernando A Palmeira , Moura Fabiana Miranda , Dias Ana Flávia Madureira de Pádua , Santoro Claudia Neiva , Pereira Fernando Henrique , Telles Rosa Weiss , Lanna Cristina Costa Duarte 
Published: October 2023

Abstract
Background: Skin manifestations occur in up to 85% of systemic lupus erythematosus (SLE) patients and can result in cutaneous atrophy and scarring, which can have a negative influence on health-related quality of life (HRQoL). Our study aims to describe HRQoL in SLE patients with permanent skin damage and explore its association with sociodemographic characteristics, self-esteem, and depression and anxiety symptoms.
Methods: Cross-sectional study of women with SLE and permanent skin damage on the face and low systemic disease activity. HRQoL was assessed by the Systemic Lupus Erythematosus Quality of Life (SLEQOL) and Dermatology Life Quality Index (DLQI) questionnaires - higher scores indicating worse HRQoL. The Rosenberg self-esteem scale was used to assess self-esteem, and depression/anxiety symptoms were assessed by the Hospital Anxiety and Depression Scale.
Results: Fifty-six consecutive patients were enrolled with a median (interquartile range - IQR) age of 47.0 (37.3 - 55.0) years and disease duration of 15.0 (8.0 - 24.8) years. The median (IQR) of the modified SLEDAI-2k was 2 (0-2) and that of the SLICC-DI was 2 (1-3). 42.8% were married, 71.4% had less than eight years of education, 71.4% were unemployed and 75.0% had a family income between 1 and 3 times the minimum wage. Higher scores in SLEQOL symptoms domain were associated with a low educational level. Higher DLQI and SLEQOL total scores were associated with low self-esteem and symptoms of depression and anxiety. SLEQOL domains, physical functioning and symptoms, were associated with low self-esteem, depression and anxiety symptoms, and the presence of scarring alopecia, whereas the activities domain was associated with low self-esteem and depression and anxiety symptoms. Mood domain was associated with low self-esteem, self-image, depression and anxiety symptoms, and treatment domain with symptoms of depression.
Conclusion: We identified low HRQoL in patients with permanent skin damage and low systemic disease activity, whether in the physical, self-image, mood or psychological domains. Associated factors were low educational level, presence of scarring alopecia, presence of anxiety and depression symptoms, and low self-esteem. These results highlight the importance of strategies to minimize the burden of permanent skin damage on the HRQoL of women with SLE.
Trial Registration: UTN code U1111-1210-2554.
BET inhibition induces synthetic lethality in PTEN deficient colorectal cancers via dual action on p21CIP1/WAF1
Authors: Shim Joong Sup , Ren Guowen , Chen Jinghong , Pu Yue , Yang Eun Ju , Tao Shishi , Mou Pui Kei , Chen Li-Jie , Zhu Wenli , Chan Kin Long , Luo Guanghui , Deng Chuxia 
Published: October 2023

Abstract
Loss of PTEN tumor suppressor is an important event during colorectal cancer (CRC) development and is a target for therapeutic exploitation. This study reports that bromodomain and extra-terminal motif (BET) is a synthetic lethal partner of PTEN in CRC. BET inhibition (BETi) selectively induced G1 cell cycle arrest and apoptosis in PTEN−/− CRC. Further, BETi selectively and dose-dependently suppressed the growth of PTEN−/− CRC tumor xenografts in mice and patient-derived organoids. Mechanistically, PTEN-deficient CRC cells elevated the level of cytoplasmic p21CIP1/WAF1 that is hyper-phosphorylated at Thr145 by AKT. BETi suppressed AKT activation in PTEN-deficient CRC cells, followed by the reduction in p21 phosphorylation at Thr145, thereby promoting its nuclear translocation. In addition, BETi suppressed MYC level and this in turn increased the total p21 level in the nuclei. Over-expression of a phospho-mimetic p21 mutant (T145D) significantly rescued the BETi effect on PTEN-deficient CRC. These results suggest that BETi has a dual action on p21: elevating the level of p21 by inhibiting MYC and converting the oncogenic (cytoplasmic) p21 into the tumor suppressive (nuclear) p21 by inhibiting AKT. Taken together, this study identified the synthetic lethal interaction between PTEN and BET, and provides a potential actionable target for CRC with PTEN loss.
Augmenting Mitochondrial Respiration in Immature Smooth Muscle Cells with an ACTA2 Pathogenic Variant Mitigates Moyamoya-like Cerebrovascular Disease
Authors: Kaw Anita , Wu Ting , Starosolski Zbigniew , Zhou Zhen , Pedroza Albert , Majumder Suravi , Duan Xue-yan , Kaw Kaveeta , Pinelo Jose Esparza , Fischbein Michael P , Lorenzi Philip , Tan Lin , Martinez Sara , Mahmud Iqbal , Devkota Laxman , Taegtmeyer Heinrich , Ghaghada Ketan , Marrelli Sean , Kwartler Callie , Milewicz Dianna 
Published: October 2023

Abstract
ACTA2 pathogenic variants altering arginine 179 cause childhood-onset strokes due to moyamoya disease (MMD)-like occlusion of the distal internal carotid arteries. A smooth muscle cell (SMC)-specific knock-in mouse model (Acta2SMC-R179C/+) inserted the mutation into 67% of aortic SMCs, whereas explanted SMCs were uniformly heterozygous. Acta2R179C/+ SMCs fail to fully differentiate and maintain stem cell-like features, including high glycolytic flux, and increasing oxidative respiration (OXPHOS) with nicotinamide riboside (NR) drives the mutant SMCs to differentiate and decreases migration. Acta2SMC-R179C/+ mice have intraluminal MMD-like occlusive lesions and strokes after carotid artery injury, whereas the similarly treated WT mice have no strokes and patent lumens. Treatment with NR prior to the carotid artery injury attenuates the strokes, MMD-like lumen occlusions, and aberrant vascular remodeling in the Acta2SMC-R179C/+ mice. These data highlight the role of immature SMCs in MMD-associated occlusive disease and demonstrate that altering SMC metabolism to drive quiescence of Acta2R179C/+ SMCs attenuates strokes and aberrant vascular remodeling in the Acta2SMC-R179C/+ mice.
Drug-associated Porphyria: A Pharmacovigilance Study
Authors: wang qi , zhuang ling jun , han bing , chen miao , zhao bin 
Published: October 2023

Abstract

Background: The potentially fatal attacks experienced by carriers of porphyria are triggered by various porphyrinogenic drugs; however, it is difficult to determine the safety of a particular drug.
Mothed: we retrospectively used the FDA’s Adverse Event Reporting System (FAERS) to determine drugs associated with porphyria as an adverse event (AE). Reports with porphyria as an AE were extracted from FAERS data from January 2004 to March 2022. Search terms used to identify the AEs included “Porphyria,” “Porphyria screen,” “Porphyria non-acute,” “Porphyria acute,” “Acquired porphyria,” and “Pseudoporphyria.” Signal mining analysis was performed to identify the association between drugs and AEs by four algorithms “ROR,” “PRR,” “BCPNN,” and “MGPS.”
Results: FAERS reported 1470 cases of porphyria-related AEs and 406 drugs were obtained after combining trade and generic names of the same drug. Fifty-two drugs with signals were identified by all four algorithms. The characteristics of all the reports and signaling drugs were analyzed.
Conclusions: This is the first report of drug-associated porphyria analysis, that provides critical information on drug porphyrogenicity, thus allowing rational and evidence-based prescribing of drugs and improving the accuracy of predicted porphyrogenicity by model algorithms. In addition, this study provides references for clinicians to ensure that porphyrinogenic drugs are not prescribed to carriers of porphyria genetic mutations.
A comparative trial of blood pressure monitoring in a self- care kiosk, in office, and with ambulatory blood pressure monitoring
Authors: Nilsson Gunnar , Lindam Anna 
Published: October 2023

Abstract
Background: If kiosk blood pressure (BP) monitoring provides results equivalent to daytime ambulatory BP monitoring (ABPM), follow-up of patients could be managed primarily by self-checks. We therefore designed a trial of automated BP monitoring in three settings: a designated BP kiosk, by nurses and physicians in clinic, and by ABPM. We also evaluated the diagnostic performance of kiosk- and office-based BP (nurse- versus physician-measured) compared with ABPM.
Methods: In-office and in-kiosk BP measurements were taken with Omron meters and ABPM with a Meditech device. The primary outcome was systolic and diastolic BP, with respective diagnostic thresholds of ≥135 mmHg and/or ≥85 mmHg for daytime ABPM and kiosk BP and ≥140 mmHg and/or ≥90 mmHg for office BP (nurse- and physician-measured).
Results: Compared with daytime ABPM, mean systolic kiosk BP was higher by 6.2 mmHg (95% confidence interval [CI] 3.8–8.6) and diastolic by 7.9 mmHg (95% CI 6.2–9.6; p < 0.001). Mean systolic BP taken by nurses was similar to daytime ABPM values (+2.0 mmHg; 95% CI -0.2–4.2; p = 0.071), but nurse-measured diastolic values were higher, by 7.2 mmHg (95% CI 5.9–9.6; p < 0.001). Mean systolic and diastolic physician-measured BPs were higher compared with daytime ABPM (systolic, by 7.6 mmHg [95% CI 4.5–10.2] and diastolic by 5.8 mmHg [95% CI 4.1–7.6]; p < 0.001). Receiver operating characteristic curves of BP monitoring across pairs of systolic/diastolic cut-off levels among the three settings, with daytime ABPM as reference, demonstrated overall similar diagnostic performance between kiosk and nurse-measured values and over the curve performance for physician-measured BP. Accuracy with nurse-measured BP was 69.2% (95% CI 60.0%–77.4%), compared with 65.8% (95% CI 56.5%–74.3%) for kiosk BP.
Conclusions: Kiosk BP monitoring is not comparable to daytime ABPM but can be an alternative to in-office BP monitoring by trained nurses.
The diagnostic performance of kiosk and nurse-measured BP monitoring was similar and better than that of physician-measured BP.
Trial registration: The study was registered at ClinicalTrials.gov (NCT04488289) 27/07/2020.
Decreased long-chain acyl-CoA dehydrogenase mediates cardiac energy deficiency and injury induced by β-adrenergic stimulation
Authors: Xiao Han , Xu Wenli , Zhao Mingming , Zhang Mi , Chen Xianda , Song Yao , Liu Huirong , Dong Erdan , Zhang You-Yi 
Published: October 2023

Abstract
Background: Overactivation of β-adrenergic receptor (β-AR) signaling underlies the cardiotoxic effects of sympathetic hyperactivity in cardiovascular disease. However, the mechanism through which metabolic changes caused by β-AR overactivation leads to cardiac injury is poorly understood.
Methods: A comprehensive multi-omics profile was performed on myocardial tissue following exposure to isoproterenol (ISO, a β-AR agonist). Cardiac-specific overexpression or downregulation of the relevant metabolic enzyme was established to investigate the mechanism. During ISO stimulation, profiles for substrate oxidation and ATP production in cardiomyocytes were also examined.
Results: Through a non-targeted metabolomics approach, lipids were identified as the most significantly affected metabolites in mouse hearts following β-AR overactivation, and subsequent targeted lipidomics analysis revealed that acylcarnitine levels were most notably elevated. Consistent with these results, patients with acute coronary syndrome showed a higher circulating acylcarnitine profile which correlated with catecholamine levels and cardiac pathologies. Mechanistic studies found that excess acylcarnitine exposure triggered inflammasome-dependent cardiomyocyte pyroptosis. Expression level of long-chain acyl-coenzyme A dehydrogenase (LCAD), an enzyme that metabolizes acylcarnitines, was markedly decreased in cardiomyocytes upon β-AR overactivation. Furthermore, ISO inhibited LCAD enzymatic activity by inhibiting sirtuin 3-mediated deacetylation, leading to ATP deficiency and acylcarnitine accumulation. Activation of AMP-activated protein kinase (AMPK) attenuated the effects of ISO on cardiomyocytes that reduced LCAD, ATP depletion, acylcarnitine-induced pyroptosis, and cardiac dysfunction in vivo.
Conclusions: Upon β-AR overactivation, decreased LCAD in cardiomyocytes leads to energy deficiency and pyroptosis, subsequently impair cardiac function. Upregulation of LCAD by AMPK activators may be a therapeutic strategy for treating sympathetic stress-induced cardiac injury.
Can pre-treatment assessment of aqueous vascular and inflammatory biomarkers in patients with macular oedema secondary to retinal vein occlusion guide treatment options?
Authors: Shankar Jai , Hughes Stephen , Ella-Tongwiis Peter 
Published: October 2023

Abstract
Background: Macular oedema following Retinal Vein occlusion is the second most common cause of visual loss due to retinal vascular disease. The Royal College of Ophthalmologists recommends intra-vitreal anti-Vascular Endothelial Growth Factor (anti-VEGF) for patients with glaucoma and in young patients & steroid injections in those with recent cardiovascular events. Treatment is, both, expensive and demanding on secondary care. There is no recommendation regarding pre-treatment biomarker testing to determine which would be a better treatment option.

Aims: The study aimed to determine whether vascular and inflammatory biomarkers in BRVO and CRVO differ from normal levels, and whether one can formulate an individualised treatment plan to predict whether anti-VEGF or steroids are more likely to be beneficial.

Methods: Eight patients each with newly diagnosed BRVO and CRVO with macular oedema without any previous intra-vitreal injections were recruited (n=16). 100-200μl of aqueous sample was taken from the anterior chamber just prior to intra-vitreal injection of anti-VEGF agent or steroid. Aqueous samples were also collected from eight patients undergoing routine cataract surgery (n=8). ELISA was employed to assess the samples for VEGF and IL-8 levels.

Results: VEGF and IL-8 levels were significantly higher in RVO as compared to controls and higher in CRVO as compared to BRVO. There were some samples with predominance of VEGF and others with IL-8.

Conclusion: This study concludes that pre-treatment assessment of biomarkers may help determine whether anti-VEGF or steroid would be a better treatment option and thereby result in a significant cost reduction for the healthcare provider.
Evaluating the impact of technological innovation and energy efficiency on load capacity factor: Empirical analysis of India
Authors: Özkan Oktay , Saleem Faiza , Sharif Arshian 
Published: October 2023

Abstract
The determinants of environmental degradation have been investigated many times by utilizing carbon dioxide emissions and/or ecological footprint. However, these traditional environmental degradation indicators do not consider the supply side of environmental problems. Therefore, this study focuses on the dynamic influence of financial development, energy efficiency, economic growth, and technological innovation on environmental degradation in India through the load capacity factor, including both supply and demand sides of environmental problems. For that purpose, the recently developed dynamically simulated autoregressive distributed lag (ARDL) method is employed using the annual time-series data extending from 1980–2020. The dynamically simulated ARDL results demonstrate that financial development, economic growth, and technological innovation have a dynamic adverse impact on the load capacity factor, whereas energy efficiency has a positive dynamic influence on environmental quality. In addition, the results support the validity of the environmental Kuznets curve hypothesis as the negative effect of economic growth on environmental quality decreases over time. Based on the study findings, policy recommendations are provided for India. Finally, this study utilizing load capacity factor as an indicator for environmental quality will provide new topics in exploring the determinants of environmental degradation.
Nanoparticles' Role in Advancing Agriculture: A comparative study of green and chemically synthesized nanoparticles and their influence on root and shoot morphology of Sunflower
Authors: Pruthviraj N , Geetha K N , Kumar G N Anil , Shruthi D L , Shankar A G , Prakash S S , Sridh Shankarappa , Raghu A V 
Published: October 2023

Abstract
The eco-friendly synthesis approach was employed to create nanoparticles by harnessing the inherent properties of natural sources. Cassia fistula leaf extract was utilized for boron nitride production, while Simarouba glauca was employed for sulphur nanoparticles. The nanoparticles' characterization involved identifying functional groups through various analytical techniques, including FT-IR, Raman spectroscopy, and UV-visible spectroscopy. Furthermore, ab initio studies were conducted to uncover the electronic properties of the boron nitride and sulphur nanostructures. The structural analysis of the boron nitride nanoparticles revealed a hexagonal configuration through Powder X-ray diffraction tests, while the sulphur nanoparticles exhibited an orthorhombic structure. In-depth examinations utilizing scanning electron microscopy and transmission electron microscopy showcased particle sizes below 100 nm. In a laboratory experiment, sunflower seeds treated with 1500 ppm green-synthesized nano boron nitride demonstrated remarkable root morphology and achieved the highest germination percentage of an impressive 98.2%, surpassing other concentration levels. Importantly, the eco-friendly synthesized nanoparticles displayed greater efficacy when compared to both chemically synthesized nanoparticles and conventional fertilizers.
Dietary intake of whale oil containing ω-3 long-chain polyunsaturated fatty acids attenuates choroidal neovascularization in mice
Authors: Yanai Ryoji , Yasunaga Genta , Tsuji Shunya , Honda Takeshi , Iwata Arihiro , Miyagawa Eiji , Yoshida Koji , Kishimoto Mitsuhiro , Sakai Hiroki , Fujise Yoshihiro , Asagiri Masataka , Kimura Kazuhiro 
Published: October 2023

Abstract
Dietary ω-3 long-chain polyunsaturated fatty acids (LCPUFAs) protect against age-related macular degeneration (AMD). We here examined the effects of whale oil, which contains ω-3 LCPUFAs, in a mouse model of AMD. Mice were fed either a diet supplemented with whale oil or a control diet free of ω-3 LCPUFAs beginning 2 weeks before induction of choroidal neovascularization (CNV) by laser photocoagulation. The area of CNV measured in choroidal flat-mount preparations at 7 days after laser photocoagulation was significantly smaller in mice fed whale oil compared with control mice. The plasma concentrations of ω-3 LCPUFAs were higher, whereas those of ω-6 LCPUFAs were lower, in mice fed the diet containing whale oil than in those fed the control diet. The concentrations of various inflammatory cytokines and chemokines in the retina or choroid at 3 or 7 days after CNV induction differed between the two groups of mice. Furthermore, the concentration of vascular endothelial growth factor (VEGF) was decreased in the retina but increased in the choroid at 7 or 3 days after photocoagulation, respectively. Our results thus show that dietary intake of whale oil containing ω-3 LCPUFAs attenuated CNV in association with changes in inflammatory mediator levels and VEGF expression in the retina and choroid of mice, and that it therefore warrants further study as a means to protect against AMD in humans.
HRH4 may be a new predictor for preterm birth
Authors: Peng Juan , Yu Caixian , Wang Huizi , Dong Xudong 
Published: October 2023

Abstract
Background
Preterm birth remains a significant contributor to infant morbidity and mortality rates worldwide. It is the primary cause of neonatal deaths and is second only to pneumonia in causing deaths in children under the age of five. The main objective of this study was to identify potential genes associated with preterm birth, with the aim of gaining insight into its underlying mechanisms.
Methods
We retrieved the mRNA dataset GSE960863 from the Gene Expression Omnibus (GEO) database, subsequently identified differentially expressed genes (DEGs) between preterm and full-term birth cohorts. We employed least absolute shrinkage and selection operator (LASSO) regression analysis, support vector machine-recursive feature elimination (SVM-RFE), and random forest methodologies to discern the central hub gene. The diagnostic potential of this hub gene was evaluated using receiver operating characteristic (ROC) analysis. Furthermore, we harnessed CIBERSORT to gauge the density of infiltrating immune cells (IICs), probing the relationship between our identified hub genes and IICs. Utilizing the GSE108876 miRNA database, we constructed an miRNA-mRNA regulatory framework on the Cytoscape platform. To validate our results, we assessed the expression levels of the hub genes via qPCR within a cohort of 68 patients from our facility, comprising 31 preterm and 37 full-term pregnancies
Result
Our analysis identified a total of 329 differentially expressed genes (DEGs). From the interplay of LASSO, SVM-RFE, and random forest methods, HRH4 emerged as the central hub gene. ROC analysis further validated HRH4's efficacy in diagnosing preterm birth, with an AUC of 0.834. Moreover, a differential infiltration of seven immune cell types was observed between the control and preterm birth groups: these included memory B cells, CD8 T cells, naive CD4 T cells, resting memory CD4 T cells, monocytes, activated mast cells, and neutrophils. Pearson's correlation underscored a significant association between HRH4 and both resting memory CD4 T cells and monocytes. Delving deeper, a miRNA-mRNA network was articulated, pinpointing seven miRNAs that exhibited an inverse regulatory pattern with HRH4 gene expression. Furthermore, clinical specimen validation revealed a statistically significant upregulation of HRH4 mRNA expression in the preterm group (p༜0.001).
Conclusion
HRH4 may serve to predict the PTB development and provide a new therapeutic target for PTB.