bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glucose-activatable insulin delivery with charge-conversional polyelectrolyte multilayers for diabetes care
Authors: Yang Yanguang , Wang Xiangqian , Yuan Xiaopeng , Zhu Qiwei , Chen Shusen , Xia Donglin 
Published: September 2022

One of the most effective treatments for diabetes is to design a glucose-regulated insulin (INS) delivery system that could adjust the INS release time and rate to reduce diabetes-related complications. Here, mixed multiple layer-by-layer (mmLbL)-INS microspheres were developed for glucose-mediated INS release and an enhanced hypoglycemic effect for diabetes care. To achieve ultrafast glucose-activated INS release, glucose oxidase (GOx) was assembled with a positively charged polymer and modified on INS LbL. The mmLbL-INS microspheres were constructed with one, two, and four layers of the polyelectrolyte LbL assembly at a ratio of 1:1:1. Under hyperglycemia, GOx converts a change in the hyperglycemic environment to a pH stimulus, thus providing sufficient hydrogen ion. The accumulated hydrogen ion starts LbL charge shifting, and anionic polymers are converted to cationic polymers through hydrolytic cleavage of amine-functionalized side chains. The results of in vitro INS release suggested that glucose can modulate the mmLbL-INS microspheres in a pulsatile profile. In vivo studies validated that this formulation enhanced the hypoglycemic effect in STZ-induced diabetic rats within 2 h of subcutaneous administration and facilitated stabilization of blood glucose levels for up to 2 days. This glucose-activatable LbL microsphere system could serve as a powerful tool for constructing a precisely controlled release system.
Evaluation of crack propagation in concrete bridges from vehicle-mounted camera images using deep learning and image processing
Authors: Nomura Yasutoshi , Inoue Masaya , Furuta Hitoshi 
Published: September 2022

In Japan, all bridges should be inspected every 5 years. Usually, the inspection has been performed through the visual evaluation of experienced engineers. However, it requires a lot of load and expense. In order to reduce the inspection work, an attempt is made in this paper to develop a new inspection method using deep learning and image processing technologies. While using the photos obtained by vehicle-mounted camera, the damage states of bridges can be evaluated manually, it still requires a lot of time and load. To save the time and load, deep learning, which is a method of artificial intelligence is introduced. For image processing, it is necessary to utilize such pre-processing techniques as binarization of pictures and morphology treatment. To illustrate the applicability of the method developed here, some experiments are conducted by using the photos of running surface of concrete bridges of a monorail took by vehicle-mounted camera.
Left ventricular assist device bioinformatics identify possible hubgenes and regulatory networks involved in the myocardium of patients with left ventricular assist device
Authors: Ajmal Maryam , Ajmal Aisha , Rizvi Maryam , Salim Umar , Huang Lei 
Published: September 2022

ObjectiveThe aim of this study was to clarify the changes of myocardial gene expression profile after left ventricular assist device (LVAD) implantation and the related molecular biological significance.MethodsA thorough bioinformatic analysis to evaluate the changes in gene expression profile in patients pre-LVAD and post-LVAD was conducted. Four relevant gene expression datasets—GSE430, GSE974, GSE21610, and GSE52601 from Gene Expression Omnibus (GEO) database were downloaded. Analysis of GEO2R, Gene Ontology (GO), protein-protein interaction (PPI) were used to determine differentially expressed genes (DEGs) and their function, respectively.ResultsA total of 37 DEGs were identified, including 26 down-regulated and 11 up-regulated genes. The molecular function of DEGs were enriched in “cytokine activity,” “neurotransmitter binding,” “receptor ligand activity.” The gene set enrichment analysis (GSEA) revealed an overall marked increase of neutrophil degranulation signaling, closely correlated with the G protein coupled receptor (GPCR)—ligand binding process after LVAD assistance. 16 hubgenes in these DEGs were further selected and the biological process involved is mainly related to positive regulation of leukocyte chemotaxis mediated by chemokines.ConclusionInflammatory signaling pathway is crucial for the pathophysiology after LVAD implantation. Chemokines mediate cardiac inflammatory response and tissue remodeling after LVAD implantation through GPCR—ligand binding.
Sub-satisfactory recanalization of severe middle cerebral artery stenoses can significantly improve hemodynamics
Authors: Zhang Kun , Ren Wei , Li Tian-Xiao , Wang Zi-Liang , Gao Bu-Lang , Xia Jin-Chao , Gao Hui-Li , Wang Yong-Feng , Gu Jian-Jun 
Published: September 2022

PurposeTo investigate the effect of sub-satisfactory stent recanalization on hemodynamic stresses for severe stenoses of the middle cerebral artery (MCA) M 1 segment.Materials and methodsPatients with severe stenoses of the MCA M1 segment treated with endovascular stent angioplasty were retrospectively enrolled. Three-dimensional digital subtraction angiography before and after stenting was performed; the computational fluid dynamics (CFD) analysis of hemodynamic stresses at the stenosis and normal segments proximal and distal to the stenoses was analyzed.ResultsFifty-one patients with severe stenosis at the MCA M1 segment were enrolled, with the stenosis length ranging from 5.1 to 12.8 mm (mean 9 ± 3.3 mm). Stent angioplasty was successful in all (100%) the patients. The angiography immediately after stenting demonstrated a significant (P &lt; 0.05) decrease in MCA stenosis after comparison with before stenting (31.4 ±12.5% vs. 87.5 ± 9.6%), with residual stenosis of 15–30% (mean 22.4 ± 3.5%). Before stenting, the total pressure was significantly higher (P &lt; 0.0001), while the WSS, velocity, and vorticity were all significantly decreased (P &lt; 0.0001) at the normal arterial segment proximal to the stenosis, and the total pressure, WSS, velocity, and vorticity were all significantly decreased (P &lt; 0.0001) at the normal arterial segment distal to the stenosis compared with those at the stenosis. After sub-satisfactory stenting recanalization, all the hemodynamic stresses proximal or distal to the stenosis and at the perforator root were improved compared with those before stenting and were similar to those after virtual stenosis removal.ConclusionSub-satisfactory recanalization of severe MCA stenoses can significantly improve the hemodynamic status for cerebral perfusion at the stenoses.
Inflammatory cytokines are associated to lower glomerular filtration rate in patients with hypertensive crisis
Authors: Andrade Days O. , Aguiar Franciana L. , Mansor Ana Luiza P. , Valente Flavia M. , Souza Doroteia R. S. , Lopes Valquiria da Silva , Fernandes Leticia B. , Godoy Moacir F. , Yugar-Toledo Juan C. , Cosenso-Martin Luciana N. , Vilela-Martin Jose F. 
Published: September 2022

IntroductionHypertension and kidney function are closely related. However, there are few studies on renal function during acute elevation of blood pressure (BP), denominated hypertensive crisis (HC).ObjectivesTo evaluate the relationship between renal function and inflammatory cytokines in HC, subdivided into hypertensive urgency (HUrg) and emergency (HEmerg).Materials and methodsThis cross-sectional study was carried out in 74 normotensive (NT) and 74 controlled hypertensive individuals (ContrHT) followed up in outpatient care. Additionally, 78 subjects with hypertensive emergency (HEmerg) and 50 in hypertensive urgency (HUrg), attended in emergency room, were also evaluated. Hypertensive crisis was classified into HEmerg, defined by systolic blood pressure (BP) ≥ 180 mmHg and/or diastolic BP ≥ 120 mmHg in presence of target-organ damage (TOD), and HypUrg, clinical situation with BP elevation without TOD. The glomerular filtration rate (eGFR) was estimated, and cytokine levels were measured. Statistical analysis was performed using the Kruskal-Wallis or Mann-Whitney test and Spearman’s correlation, with significant differences p-value &lt; 0.05.ResultsThe median age was 53.5 years in the NT group (52 female), 61 years in the ContrHT group (52 female), and 62.5 years in the HC group (63 female) (p-value &lt; 0.0001). The median BP was 118.5/75 mmHg for NT, 113.5/71 for ContrHT, and 198.5/120 mmHg for HC, respectively (p-value &lt; 0.0001 among groups). BP and heart rate levels were significantly higher in the HC group compared to the NT and ContrHT groups (P &lt; 0.001 for all). The eGFR was significantly lower in HC group compared to the NT and ContrHT groups. The cytokine levels were higher in the HEmerg and HUrg groups compared to ContrHT group (P &lt; 0.0001, except for IL-1β in HUrg vs. ContrHT), without difference between the acute elevation of BP groups. Thus, all cytokines were significantly elevated in patients with HC compared to the control groups (NT and ContrHT). There was a negative correlation between eGFR and the cytokines (IL-1β, IL-6, IL-8, IL-10, and TNF-α) in the HC group.ConclusionElevated inflammatory cytokines are associated with reduced eGFR in individuals with HC compared to control groups, suggesting that the inflammatory process participates in the pathogenesis of acute elevations of BP.
Cardiovascular drug interventions in the cardio-oncology clinic by a cardiology pharmacist: ICOP-Pharm study
Authors: Yaseen Israa Fadhil , Farhan Hasan Ali 
Published: September 2022

BackgroundCardio-oncology is a rapidly growing field that requires a novel service design to deal with the increasing number of patients. It is reported that the volume of patients at the cardio-oncology clinic in the United Kingdom is 535 patients/5 years and in Canada is 779 patients/7 years. The pharmacist has a role in reducing the consultation time of physicians.ObjectiveTo identify the role of a qualified cardiology pharmacist at the cardio-oncology clinic using a new paradigm based on complementary interventions with the cardiologist for the management of patients with cancer and cardiovascular risk factors and/or cardiovascular diseases (CVRF/CVD).MethodsA prospective observational study was conducted at the cardio-oncology clinic in the Medical City in Baghdad, Iraq between December 2020 and December 2021. Patients with CVRF/CVD were registered. The Iraqi Cardio-Oncology Program-Pharmacist (ICOP-Pharm) paradigm was designed to involve a qualified cardiology pharmacist for initial cardiovascular (CV) drug interventions.ResultsAmong 333 patients who attended our clinic over the 1-year interval, 200 (60%) CVRF/CVD cases were enrolled in the study, and of them 79 (40%) patients had CV drug interventions. A total of 196 interventions were done, including 147 (75%) cases performed by the cardiology pharmacist, and 92 (63%) of the latter were CV drug initiations. Among the total CVRF/CVD treated initially by the cardiology pharmacist, hypertension 32 (26%) and cancer therapy-related cardiac dysfunction 29 (24%) were the main types.ConclusionThe qualified cardiology pharmacist was responsible for three-quarters of the initial CV drug interventions at the cardio-oncology clinic in a complementary approach to the cardiologist. The role of the cardiology pharmacist in the ICOP-Pharm paradigm may be one of the reasons for the ability of the heart team to manage 3-fold of the patient volume when compared with those in the United Kingdom or Canada.
AST-to-ALT ratio in the first trimester and the risk of gestational diabetes mellitus
Authors: An Rongjing , Ma Shujuan , Zhang Na , Lin Huijun , Xiang Tianyu , Chen Mengshi , Tan Hongzhuan 
Published: September 2022

BackgroundAspartate aminotransferase-to-alanine transaminase ratio (AST/ALT) has been reported affect the risk of type 2 diabetes (T2DM), but it is uncertain if it has relationship with gestational diabetes mellitus (GDM).ObjectivesOur study aimed to investigate the association between AST/ALT ratio in the first trimester and the risk of subsequent development of GDM.MethodThis prospective cohort study enrolling 870 pregnant women, 204 pregnant women with missing data or liver diseases were excluded, 666 pregnant women were included in this study containing 94 GDM women. Blood samples were collected in the first trimester. Univariate analysis and multivariate logistic regression were used to evaluate the association between AST/ALT and GDM. Nomogram was established based on the results of multivariate logistic analysis. Receiver Operating Characteristic (ROC) curves and calibration curves were used to evaluate the predictive ability of this nomogram model for GDM. Decision curve analysis (DCA) was used to examine the clinical net benefit of predictive model.ResultsAST/ALT ratio (RR:0.228; 95% CI:0.107-0.488) was associated with lower risk of GDM after adjusting for confounding factors. Indicators used in nomogram including AST/ALT, maternal age, preBMI, waist circumference, glucose, triglycerides, high density lipoprotein cholesterol and parity. The area under the ROC curve (AUC) value of this predictive model was 0.778, 95% CI (0.724, 0.832). Calibration curves for GDM probabilities showed acceptable agreement between nomogram predictions and observations. The DCA curve demonstrated a good positive net benefit in the predictive model.ConclusionsThe early AST/ALT level of pregnant women negatively correlated with the risk of GDM. The nomogram including AST/ALT at early pregnancy shows good predictive ability for the occurrence of GDM.
Prognostic factors and mitotane treatment of adrenocortical cancer. Two decades of experience from an institutional case series
Authors: Tőke Judit , Uhlyarik Andrea , Lohinszky Júlia , Stark Júlia , Huszty Gergely , Micsik Tamás , Borka Katalin , Reismann Péter , Horányi János , Igaz Peter , Tóth Miklós 
Published: September 2022

ObjectivesThis study aimed to characterise the clinicopathological features and prognostic factors of a large cohort of Hungarian patients with adrenocortical cancer diagnosed between 2000-2021.Patients and methodsThis retrospective study included seventy-four patients (27 men and 47 women) with histologically confirmed adrenocortical cancer in a single tertiary referral endocrine centre. Descriptive statistics were performed, providing summaries of selected clinical and pathological parameters. Clinicopathological factors contributing to overall survival were analysed.ResultsThe median age of patients was 48,5 years (17-84 years) at diagnosis. The majority of cases were diagnosed at ENSAT stage II (39,2%) and stage IV (33,8%). At diagnosis, the median tumour size was 9,0 cm (4,5-20 cm). In 47 patients (71,6%), the tumour was hormonally active. The median overall survival and the 5-year survival rate were 23,5 months (95% CI, 17-30,5 months) and 18,3%, respectively. Primary tumour resection was performed in 68 patients (91,8%); R0 surgical resection was achieved in 30 patients. In univariate Cox regression model, tumours with stages III and IV, high proliferative activity (Ki67-index &gt; 10%), R1-R2 surgical resection state and hormonal activity were associated with poorer survival. Cortisol excess, both isolated and combined with androgen production, was associated with poorer survival. Fifty-five patients were treated with mitotane. The overall survival of patients achieving therapeutic mitotane plasma concentration was significantly better compared to those who never reached it [27.0 (2-175) months vs 18.0 (2-83) months; p&lt;0.05)]. The median age, the distribution of gender, ENSAT stage, resection state and Ki67-index did not differ between these two groups. The time needed to reach the therapeutic range of serum mitotane was 96.5 days (95% CI, 75-133 days).ConclusionOur results confirm previous data that disease stage, mitotic activity, the resection state and the mitotane treatment achieving therapeutic concentration are the most critical parameters influencing the prognosis of adrenocortical cancer. Our data suggest that hormonal activity may be more frequent than described previously, and it is a strong and independent prognostic factor of overall survival. To our knowledge, this is the first single-centre study confirming the prognostic importance of achieving therapeutic mitotane concentration.
MiR-539-3p impairs osteogenesis by suppressing Wnt interaction with LRP-6 co-receptor and subsequent inhibition of Akap-3 signaling pathway
Authors: Tripathi Alok , John Aijaz A. , Kumar Deepak , Kaushal Saurabh Kumar , Singh Devendra Pratap , Husain Nazim , Sarkar Jayanta , Singh Divya 
Published: September 2022

X-linked hypophosphatemia (XLH), an inheritable form of rickets is caused due to mutation in Phex gene. Several factors are linked to the disease’s aetiology, including non-coding RNA molecules (miRNAs), which are key post-transcriptional regulators of gene expression and play a significant role in osteoblast functions. MicroRNAs sequence analysis showed differentially regulated miRNAs in phex silenced osteoblast cells. In this article, we report miR-539-3p, an unidentified novel miRNA, in the functional regulation of osteoblast. MiR-539-3p overexpression impaired osteoblast differentiation. Target prediction algorithm and experimental confirmation by luciferase 3’ UTR reporter assay identified LRP-6 as a direct target of miR-539-3p. Over expression of miR-539-3p in osteoblasts down regulated Wnt/beta catenin signaling components and deteriorated trabecular microarchitecture leading to decreased bone formation in ovariectomized (Ovx) mice. Additionally, biochemical bone resorption markers like CTx and Trap-5b were elevated in serum samples of mimic treated group, while, reverse effect was observed in anti-miR treated animals along with increased bone formation marker P1NP. Moreover, transcriptome analysis with miR-539-3p identified a novel uncharacterized Akap-3 gene in osteoblast cells, knock down of which resulted in downregulation of osteoblast differentiation markers at both transcriptional and translational level. Overall, our study for the first time reported the role of miR-539-3p in osteoblast functions and its downstream Akap-3 signalling in regulation of osteoblastogenesis.
The serum free triiodothyronine to free thyroxine ratio as a potential prognostic biomarker of chronic kidney disease in patients with glomerular crescents: A retrospective study
Authors: Zhang Liwen , Wu Yuxiao , Nie Yuxin , Lv Wenlv , Li Yang , Zhu Bowen , Jin Shi , Shen Ziyan , Li Fang , Liu Hong , Fang Yi , Ding Xiaoqiang 
Published: September 2022

BackgroundCrescent formation indicates severe glomerular pathology, and hypothyroidism usually predicts poor prognosis for severe diseases. However, the relationship between thyroid function and the progression of chronic kidney disease (CKD) is unclear. This study analysed the prognostic predictive value of the serum free triiodothyronine (FT3) to free thyroxine (FT4) ratio and its correlation with renal function in patients with CKD with crescent formation.MethodsThis single-centre study included 162 CKD patients with glomerular crescents confirmed by renal pathology between March 2012 and December 2014. According to the first tertile (0.284) of FT3/FT4 ratio, the patients were divided into high and low FT3/FT4 ratio groups. Kaplan-Meier and Cox regression analyses were performed to evaluate the prognostic value of the FT3/FT4 ratio.ResultsThe age, haemoglobin, eGFR, urinary albumin-to-creatinine ratio, cardiac troponin T, N-terminal brain natriuretic peptide precursor, FT3, FT4, percentage of total crescents in non-globally sclerotic glomeruli, prevalences of hypertension, moderate to severe renal tubulopathy and crescentic nephritis, and proportion of patients receiving glucocorticoids and immunosuppressants were significantly different between high and low FT3/FT4 ratio groups (P &lt; 0.05). Multivariate Cox regression analysis showed that when compared with patients with a high FT3/FT4 ratio (&gt;0.284), those with intermediate and low FT3/FT4 ratios (≤0.284) had an increased risk of the long-term composite endpoint (P &lt; 0.05 for various adjustment models).ConclusionsA low FT3/FT4 ratio is associated with increased mortality and worse outcome risk in CKD patients with crescent pathology.
Two subtypes of cutaneous melanoma with distinct mutational signatures and clinico-genomic characteristics
Authors: Kim Yoon-Seob , Lee Minho , Chung Yeun-Jun 
Published: September 2022

Background: To decipher mutational signatures and their associations with biological implications in cutaneous melanomas (CMs), including those with a low ultraviolet (UV) signature.Materials and Methods: We applied non-negative matrix factorization (NMF) and unsupervised clustering to the 96-class mutational context of The Cancer Genome Atlas (TCGA) cohort (N = 466) as well as other publicly available datasets (N = 527). To explore the feasibility of mutational signature-based classification using panel sequencing data, independent panel sequencing data were analyzed.Results: NMF decomposition of the TCGA cohort and other publicly available datasets consistently found two mutational signatures: UV (SBS7a/7b dominant) and non-UV (SBS1/5 dominant) signatures. Based on mutational signatures, TCGA CMs were classified into two clusters: UV-high and UV-low. CMs belonging to the UV-low cluster showed significantly worse overall survival and landmark survival at 1-year than those in the UV-high cluster; low or high UV signature remained the most significant prognostic factor in multivariate analysis. The UV-low cluster showed distinct genomic and functional characteristic patterns: low mutation counts, increased proportion of triple wild-type and KIT mutations, high burden of copy number alteration, expression of genes related to keratinocyte differentiation, and low activation of tumor immunity. We verified that UV-high and UV-low clusters can be distinguished by panel sequencing.Conclusion: Our study revealed two mutational signatures of CMs that divide CMs into two clusters with distinct clinico-genomic characteristics. Our results will be helpful for the clinical application of mutational signature-based classification of CMs.