bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tyrosine-Protein Phosphatase Non-receptor Type 9 (PTPN9) Negatively Regulates the Paracrine Vasoprotective Activity of Bone-Marrow Derived Pro-angiogenic Cells: Impact on Vascular Degeneration in Oxygen-Induced Retinopathy
Authors: Desjarlais Michel , Ruknudin Pakiza , Wirth Maëlle , Lahaie Isabelle , Dabouz Rabah , Rivera José Carlos , Habelrih Tiffany , Omri Samy , Hardy Pierre , Rivard Alain , Chemtob Sylvain 
Published: May 2021

Background and AimInsufficient post-ischemic neovascularization is an initial key step in the pathogenesis of Oxygen-Induced Retinopathy (OIR). During neovascularization, pro-angiogenic cells (PACs) are mobilized from the bone marrow and integrate into ischemic tissues to promote angiogenesis. However, the modulation of PAC paracrine activity during OIR and the specific mechanisms involved remain to be explored. Because Tyrosine-protein phosphatase non-receptor type 9 (PTPN9) is reported to be a negative regulator of stem cell differentiation and angiogenesis signaling, we investigated its effect on PAC activity in the context of OIR.Methods and ResultsIn a rat model of OIR, higher levels of PTPN9 in the retina and in bone marrow derived PACs are associated with retinal avascular areas, lower levels of the mobilization factor SDF-1 and decreased number of CD34+/CD117+/CD133+ PACs. PACs exposed ex vivo to hyperoxia display increased PTPN9 expression, which is associated with impaired ability of PAC secretome to promote angiogenesis ex vivo (choroidal vascular sprouting) and in vitro (endothelial cell tubule formation) compared to the secretome of PACs maintained in normoxia. Suppression of PTPN9 (using siRNA) increases VEGF and SDF-1 expression to normalize PAC secretome during hyperoxia, leading to restored angiogenic ability of PAC secretome. Moreover, endothelial cells exposed to the secretome of siPTPN9-treated PACs expressed increased levels of activated form of VEGF receptor 2 (VEGFR2). In the rat model of OIR, intravitreal injection of secretome from siPTPN9-treated PACs significantly reduced retinal vaso-obliteration; this was associated with higher retinal levels of VEGF/SDF-1, and increased recruitment of PACs (CD34+ cells) to the retinal and choroidal vessels.ConclusionOur results suggest that hyperoxia alters the paracrine proangiogenic activity of BM-PACs by inducing PTPN9, which can contribute to impair post-ischemic revascularization in the context of OIR. Targeting PTPN9 restores PAC angiogenic properties, and provide a new target for vessel integrity in ischemic retinopathies.
Clinical Autopsy of a Reverse Osmosis Membrane Module
Authors: Gonzalez-Gil Graciela , Behzad Ali Reza , Farinha Andreia S. F. , Zhao Chengyan , Bucs Szilard S. , Nada Tariq , Das Ratul , Altmann Thomas , Buijs Paulus J. , Vrouwenvelder Johannes S. 
Published: May 2021

The desalination of seawater using reverse osmosis membranes is an attractive solution to global freshwater scarcity. However, membrane performance is reduced by (bio)fouling. Membrane autopsies are essential for identifying the type of fouling material, and applying corrective measures to minimize membrane fouling. Information from full-scale membrane autopsies guiding improved plant operations is scant in the formal literature. In this case-study, a reverse osmosis membrane from a full-scale seawater desalination plant with a feed channel pressure drop increase of about 218% over the pressure vessel was autopsied. The simultaneous determination of microbial cells, ATP, and total organic carbon (TOC) abundances per membrane area allowed estimating the contributions of biofouling and organic fouling. The abundance of microbial cells determined by flow cytometry (up to 7 × 108 cells/cm2), and ATP (up to 21,000 pg/cm2) as well as TOC (up to 98 μg/cm2) were homogeneously distributed on the membrane. Inorganic fouling was also measured, and followed a similar coverage distribution to that of biofouling. Iron (∼150 μg/cm2, estimated by ICP-MS) was the main inorganic foulant. ATR-FTIR spectra supported that membrane fouling was both organic/biological and inorganic. High-resolution SEM-EDS imaging of cross-sectioned membranes allowed assessing the thickness of the fouling layer (up to 20 μm) and its elemental composition. Imaging results further supported the results of homogeneous fouling coverage. Moreover, imaging revealed both zones with and without compression of the polysulfone membrane layer, suggesting that the stress due to operating pressure was heterogeneous. The procedure for this membrane autopsy provided a reasonable overview of the diverse contributors of fouling and might be a starting point to building a consensus autopsy protocol. Next, it would be valuable to build a RO membrane autopsy database, which can be used as a guidance and diagnostic tool to improve the management and operation of RO desalination plants.
Bandgap Engineering of an Aryl-Fused Tetrathianaphthalene for Visible-Blind Organic Field-Effect Transistors
Authors: Zhang Lijuan , Tian Xinzi , Sun Yantao , Yao Jiarong , Yang Shuyuan , Liu Zheyuan , Ge Zhen , Zhang Hongtao , Sun Yan , Shao Xiangfeng , Li Rongjin , Hu Wenping 
Published: May 2021

Stability problem of organic semiconductors (OSCs) because of photoabsorption has become a major barrier to large scale applications in organic field-effect transistors (OFETs). It is imperative to design OSCs which are insensitive to visible and near-infrared (VNIR) light to obtain both environmental and operational stability. Herein, taking a 2,3,8,9-tetramethoxy [1,4]benzodithiino[2,3-b][1,4]benzodithiine (TTN2) as an example, we show that controlling molecular configuration is an effective strategy to tune the bandgaps of OSCs for visible-blind OFETs. TTN2 adopts an armchair-like configuration, which is different from the prevailing planar structure of common OSCs. Because of the large bandgap, TTN2 exhibits no photoabsorption in the VNIR region and OFETs based on TTN2 show high environmental stability. The devices worked well after being stored in ambient air, (i.e. in the presence of oxygen and water) and light for over two years. Moreover, the OFETs show no observable response to light irradiation from 405–1,020 nm, which is also favorable for high operational stability.
High-Sensitivity Cardiac Troponin Predicts Major Cardiovascular Events in Diabetic Patients With Critical Limb Ischemia and Foot Lesions
Authors: Cimaglia Paolo , Dalla Paola Luca , Carone Anna , Scavone Giuseppe , Manfrini Marco , Brogneri Simona , Tenti Elena , Pavasini Rita , Bernucci Davide , Passarini Giulia , Vitali Francesco , Gaudenzi Eleonora , Ferrari Roberto , Campo Gianluca 
Published: May 2021

Background: Diabetic patients with critical limb ischemia (CLI) and foot lesions show a poor prognosis. Optimal risk stratification to guide tailored intervention is still uncertain. The aim of the present study was to assess the prognostic role of high-sensitivity cardiac troponin T (hs-TnT) in such a high-risk population.Methods and Results: Clinical, laboratory, and interventional data, as well as the SPINACH score, were collected. Hs-TnT was measured at hospital admission. All patients were followed up for at least 1 year. The primary endpoint was the cumulative occurrence of major cardiovascular events (MACEs, all-cause death, myocardial infarction, or stroke). The secondary endpoint was all-cause mortality. Overall, 618 patients were included and followed for a median of 981 (557–1,325) days. Diagnosis of coronary artery disease (CAD) was established in 270 (43.7%) patients. Median hs-TnT at admission was 31 (20–59) ng/L, with 525 (85%) patients over the upper reference limit. Hs-TnT values were significantly higher in patients with established CAD (39 vs. 29 ng/L, p &lt; 0.01). Hs-TnT was an independent predictor of MACE (HR 2.440, 95% CI 1.706–3.489, p &lt; 0.001). The best cut-offs were 40 ng/L (AUC 0.711) for patients with established CAD and 25 ng/L (AUC 0.725) for those without. Hs-TnT emerged also as an independent predictor of all-cause mortality. The addition of hs-TnT improved prognostic value of the SPINACH score.Conclusions: Hs-TnT is a powerful biomarker for prognostic stratification of diabetic CLI patients with foot lesions. This is confirmed independently to CAD diagnosis and permits the identification of higher risk patients requiring tailored intervention.
Transcriptome and N6-Methyladenosine RNA Methylome Analyses in Aortic Dissection and Normal Human Aorta
Authors: Zhou Xianwu , Chen Zerui , Zhou Jianrong , Liu Yaorong , Fan Ruixin , Sun Tucheng 
Published: May 2021

Objective: To investigate the N6-methyladenosine (m6A) modification and the expressions of the m6A regulatory genes in the acute aortic dissection (AD).Methods: MeRIP-seq and RNA-seq experiments of aortic media tissue samples obtained from AD (n = 4) and Controls (n = 4) were conducted. m6A methylation quantification was used to measure the total mRNA m6A level. The five m6A regulators mRNA expressions were analyzed by quantitative polymerase chain reaction (qPCR). Western blot analyses and immunofluorescence staining were used to detect the difference of METTL14 protein expression in the aortas of AD and Normal.Results: Among AD patients, we detected significantly elevated levels of m6A in total RNA. Compared with the normal group, the up methylated coding genes of AD were primarily enriched in the processes associated with extracellular fibril organization, while the genes with down methylation were enriched in the processes associated with cell death regulation. Furthermore, many differentially methylated m6A sites (DMMSs) coding proteins were mainly annotated during the extracellular matrix and inflammatory responses.Conclusions: These findings indicate that differential m6A methylation and m6A regulatory genes, including MTEEL14 and FTO, may act on functional genes through RNA modification, thereby regulating the pathogenesis of aortic dissection.
Leisure-Time Physical Activity and Cardiovascular Disease Risk Among Hypertensive Patients: A Longitudinal Cohort Study
Authors: Li Jiqing , Zhang Zhentang , Si Shucheng , Xue Fuzhong 
Published: May 2021

Objective: Few studies estimated the effect of leisure-time physical activity (LTPA) on cardiovascular disease (CVD) risk among hypertensive patients in a longitudinal cohort. This study aims to evaluate the association between LTPA and CVD in a longitudinal management cohort of hypertensive patients.Methods: A total of 58,167 hypertensive patients without baseline CVD from a longitudinal cohort were included in this study. LTPA and other covariates were measured at the follow-up four times annually. The primary outcome was CVD events. The association between LTPA and CVD was assessed by the marginal structure model (MSM) and Cox model with adjustment for age, gender, body mass index (BMI), smoking, drinking, diabetes, hyperlipidemia, and antihypertensive medication. The restricted cubic spline and segmented regression were used to assess the dose–response relationship between LTPA and CVD.Results: We recorded 16,332 CVD events; crude incidence of CVD were 89.68, 80.39, 62.64, and 44.04 per 1,000 person-years for baseline 0, 1–150, 151–300, and &gt;300 min/week LTPA, respectively. Compared with inactive LTPA, the adjusted hazard ratios (HRs) estimated by Cox model and MSM-Cox model for CVD associated with 1–150,151–300, and 300 min/week LTPA were 0.85 (95% CI, 0.83–0.88), 0.67 (95% CI, 0.64–0.71), 0.47 (95% CI, 0.44–0.51), and 0.83 (95% CI, 0.76–0.91), 0.58 (95% CI, 0.52–0.63), and 0.39 (95% CI, 0.35–0.44), respectively. Per 60 min/week increase in LTPA was associated with a 13% reduction in CVD risk. LTPA breakpoint was 417 min/week for CVD. Before and after the break-point, the slopes of the piecewise-linear relationship between LTPA and CVD risk were −0.0017 and −0.0003, respectively.Conclusion: LTPA was more strongly associated with the CVD risk than that estimated by conventional analyses based on baseline LTPA; 417 min/week is a breakpoint, after which the incremental health benefits on CVD prevention obtained from the increase in LTPA are much less than before.
Global Circumferential Strain by Cardiac Magnetic Resonance Tissue Tracking Associated With Ventricular Arrhythmias in Hypertrophic Cardiomyopathy Patients
Authors: Pu Cailing , Fei Jingle , Lv Sangying , Wu Yan , He Chengbin , Guo Danling , Mabombo Pierre Umba , Chooah Outesh , Hu Hongjie 
Published: May 2021

Background: Hypertrophic cardiomyopathy (HCM) is prone to myocardial heterogeneity and fibrosis, which are the substrates of ventricular arrhythmias (VAs). Cardiac magnetic resonance tissue tracking (CMR-TT) can quantitatively reflect global and regional left ventricular strain from different directions. It is uncertain whether the change of myocardial strain detected by CMR-TT is associated with VAs. The aim of the study is to explore the differential diagnostic value of VAs in HCM by CMR-TT.Materials and Methods: We retrospectively included 93 HCM patients (38 with VAs and 55 without VAs) and 30 healthy cases. Left ventricular function, myocardial strain parameters and percentage of late gadolinium enhancement (%LGE) were evaluated.Results: Global circumferential strain (GCS) and %LGE correlated moderately (r = 0.51, P &lt; 0.001). HCM patients with VAs had lower left ventricular ejection fraction (LVEF), global radial strain (GRS), GCS, and global longitudinal strain (GLS), but increased %LGE compared with those without VAs (P &lt; 0.01 for all). %LGE and GCS were indicators of VAs in HCM patients by multivariate logistic regression analysis. HCM patients with %LGE &gt;5.35% (AUC 0.81, 95% CI 0.70–0.91, P &lt; 0.001) or GCS &gt;-14.73% (AUC 0.79, 95% CI 0.70–0.89, P &lt; 0.001) on CMR more frequently had VAs. %LGE + GCS were able to better identify HCM patients with VAs (AUC 0.87, 95% CI 0.79–0.95, P &lt; 0.001).Conclusion: GCS and %LGE were independent risk indicators of VAs in HCM. GCS is expected to be a good potential predictor in identifying HCM patients with VAs, which may provide important values to improve risk stratification in HCM in clinical practice.
Effects of U-Mo Irradiation Creep Performance on the Thermo-Mechanical Coupling Behavior in U-Mo/Al Monolithic Fuel Assemblies
Authors: Mao Xiaoxiao , Jian Xiaobin , Zhang Jingyu , Yan Feng , Ding Shurong , Huo Yongzhong , Wang Haoyu , Zhang Lin , Li Yuanming 
Published: May 2021

To obtain the optimized fuel performance, the effects of U-Mo irradiation creep rate coefficient on the thermo-mechanical behavior of a fuel assembly are investigated. In this study, three cases of creep rate coefficient are considered. The distribution and evolution results of temperature, displacement, stress/strain and fuel foil micro-structure are analyzed. The simulation results indicate that with the increase of creep rate coefficient 1) the temperature field in the fuel assembly changes slightly; 2) the maximum out-of-plane displacements in the side plates decrease slightly; the maximum out-of-plane displacements in the fuel plates adjacent to the outside Al plates rise distinctly, induced by the enhanced bending deformation contributions; 3) the peak values of the first principal stresses and skeleton normal stresses in the fuel foils are reduced, while the through-thickness creep strains are enlarged; 4) with an increase of fuel creep rate coefficient from 500 × 10−22 mm3/(fission MPa) to 2,000 × 10−22 mm3/(fission·MPa), the maximum Von Mises stress in the fuel cladding decreases by ∼24% on the 308th day. This work is helpful for advanced fabrication and optimization design of U-Mo/Al fuel assemblies.
SMARThealth Pregnancy: Feasibility and Acceptability of a Complex Intervention for High-Risk Pregnant Women in Rural India: Protocol for a Pilot Cluster Randomised Controlled Trial
Authors: Nagraj Shobhana , Kennedy Stephen H. , Jha Vivekananda , Norton Robyn , Hinton Lisa , Billot Laurent , Rajan Eldho , Arora Varun , Praveen Devarsetty , Hirst Jane E. 
Published: May 2021

Introduction: India is in the process of a major epidemiological transition towards non-communicable diseases. Cardiovascular disease (CVD) is the leading cause of death in women in India. Predisposing independent risk factors include pregnancy-related conditions, e.g., hypertensive disorders of pregnancy (HDP) and gestational diabetes (GDM) - also associated with significant perinatal mortality and morbidity. Early identification, referral and management of pregnant women at increased risk of future CVD may offer opportunities for prevention. In rural India, Community Health Workers (CHWs) provide most antenatal and postnatal care. Innovative solutions are required to address integrated care for rural women during transitions between antenatal, postnatal and general health services. The George Institute's SMARThealth Programme has shown that CHWs in rural India screening non-pregnant adults for cardiovascular risk, using a decision support system, is feasible. Building on this, we developed a targeted training programme for CHWs and a complex system-level intervention that uses mobile clinical decision support for CHWs and primary care doctors to screen high-risk pregnant women. In addition to addressing HDP and GDM, the intervention also screens for anaemia in pregnancy.Methods/Design: A pilot study will be undertaken in two diverse rural districts of India: Jhajjar (Haryana) and Guntur (Andhra Pradesh). Two Primary Health Centre clusters will be randomised to intervention or control groups at each study site. The primary objective of this pilot study is to explore the feasibility and acceptability of the SMARThealth Pregnancy intervention. Secondary objectives are to estimate: (a) prevalence rates of moderate to severe anaemia, HDPs and GDM at the study sites; (b) referral and follow-up rates, and (c) mean haemoglobin and blood pressure values at the routine 6 week postnatal visit. A process evaluation will be conducted to explore the acceptability of the SMARThealth Pregnancy intervention for pregnant women and healthcare workers using qualitative methods.Discussion: It is anticipated that the findings of this pilot study will help determine the feasibility and acceptability of the SMARThealth Pregnancy intervention, and highlight how the intervention might be further developed for evaluation in a larger, cluster randomised controlled trial.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT03968952.
LPS Mediates Bovine Endometrial Epithelial Cell Pyroptosis Directly Through Both NLRP3 Classical and Non-Classical Inflammasome Pathways
Authors: Ma Xiaoyu , Li Yajuan , Shen Wenxiang , Oladejo Ayodele Olaolu , Yang Jie , Jiang Wei , Imam Bereket Habte , Wu Xiaohu , Ding Xuezhi , Yang Ying , Wang Shengyi , Yan Zuoting 
Published: May 2021

As a highly inflammatory form of programmed cell death, pyroptosis is triggered by pro-inflammatory signals and associated with inflammation. It is characterized by cell swelling and large bubbles emerging from the plasma membrane, which release cytokines during inflammation. Compared with other types of cell death, pyroptosis has a distinct morphology and mechanism and involves special inflammasome cascade pathways. However, the inflammasome mechanism through which endometrial epithelial cell pyroptosis occurs in LPS-mediated inflammation remains unclear. We confirmed that there was an increased mRNA and protein expression of the IL-6, TNF-α, IL-1β, IL-18 cytokines, the inflammasome molecules NLRP3, CASPASE-1, CASPASE-4, and GSDMD in LPS-induced primary bovine endometrial epithelial cells (BEECs) in an in vitro established inflammatory model using ELISA, real-time PCR (RT-PCR), vector construction and transfection, and Western blotting. Scanning electron microscopy and lactate dehydrogenase (LDH) activity assays revealed induced cell membrane rupture, which is the main characteristic of pyroptosis. In conclusion, the cytolytic substrate GSDMD’s cleavage by caspase-1 or caspase-4 through the NLRP3 classical and non-classical inflammasome pathways, GSDMD N-terminus bind to the plasma membrane to form pores and release IL -18, IL-1β cause cell death during LPS induced BEECs inflammation.
Sex-Based Differences in pH Parameters and Esophageal Impedance of Patients With Gastroesophageal Reflux Disease
Authors: Ye Bixing , Wang Yanjuan , Lin Lin , Jiang Liuqin , Wang Meifeng 
Published: May 2021

Background/Aims: The incidence of reflux esophagitis (RE) has a striking predominance in males. Conversely, non-erosive reflux disease (NERD) is more common in females. This imbalance of gastroesophageal reflux disease (GERD) implies sex-related differences in its pathogenesis. However, limited studies have analyzed the sex-based differences in pH parameters and esophageal impedance of GERD patients.Methods: This study evaluated sex-based pathogenesis differences by comparing reflux episodes, mean nocturnal baseline impedance (MNBI) values, and post-reflux swallow-induced peristaltic wave (PSPW) index values of males with GERD and females with GERD using 24-h multichannel intraluminal impedance and pH monitoring.Results: We analyzed 181 patients (102 males and 79 females) with GERD. Reflux symptom index (RSI) scores were higher in females than that in males (P &lt; 0.05). Males had significantly longer acid exposure times, higher DeMeester scores, and more acid reflux episodes than females (P &lt; 0.05). Females had more instances of weakly acidic reflux than males (P &lt; 0.01). The PSPW index values of males and females were similar (P &gt; 0.05). Compared with females, males had lower MNBI values for the mid and distal esophagus (P &lt; 0.05). However, with increasing age, the MNBI values of females decreased more rapidly than those of males. MNBI values of elderly patients of both sexes older than 60 years were similar.Conclusions: Acid reflux is more likely to occur in males; however, females tend to have more instances of weakly acid reflux. The integrity of the esophageal mucosa is more fragile in males than in females; however, the esophageal mucosal barrier attenuates more rapidly with increasing age in females than in males.