bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nicotine Modulates CTSS (Cathepsin S) Synthesis and Secretion Through Regulating the Autophagy-Lysosomal Machinery in Atherosclerosis
Authors: Ni Huaner , Xu Shuang , Chen Hangwei , Dai Qiuyan 
Published: July 2020

Objective:
Increased CTSS (cathepsin S) has been reported to play a critical role in atherosclerosis progression. Both CTSS synthesis and secretion are essential for exerting its functions. However, the underlying mechanisms contributing to CTSS synthesis and secretion in atherosclerosis remain unclear.

Approach and Results:

In this study, we showed that nicotine activated autophagy and upregulated CTSS expression in vascular smooth muscle cells and in atherosclerotic plaques. Western blotting and immunofluorescent staining showed that nicotine inhibited the mTORC1 (mammalian target of rapamycin complex 1) activity, promoted the nuclear translocation of TFEB (transcription factor EB), and upregulated the expression of CTSS. Chromatin immunoprecipitation-qualificative polymerase chain reaction, electrophoretic mobility shift assay, and luciferase reporter assay further demonstrated that TFEB directly bound to the
CTSS
promoter. mTORC1 inhibition by nicotine or rapamycin promoted lysosomal exocytosis and CTSS secretion. Live cell assays and IP-MS (immunoprecipitation-mass spectrometry) identified that the interactions involving Rab10 (Rab10, member RAS oncogene family) and mTORC1 control CTSS secretion. Nicotine promoted vascular smooth muscle cell migration by upregulating CTSS, and CTSS inhibition suppressed nicotine-induced atherosclerosis in vivo.

Conclusions:
We concluded that nicotine mediates CTSS synthesis and secretion through regulating the autophagy-lysosomal machinery, which offers a potential therapeutic target for atherosclerosis treatment.
Acquired von Willebrand Syndrome Hiding Inherited von Willebrand Disease Can Explain Severe Bleeding in Patients With Aortic Stenosis
Authors: Casonato Alessandra , Galletta Eva , Cella Giuseppe , Barbon Giovanni , Daidone Viviana 
Published: July 2020

Objective:
Aortic stenosis may be complicated by an acquired von Willebrand syndrome that rarely causes significant bleeding, raising the question of why it does so in a few cases. To seek an explanation, we studied 5 severe bleeder aortic stenosis patients in a cohort of 49 patients, using the flowchart for inherited von Willebrand disease.

Approach and Results:
All 5 patients were lacking in large and intermediate VWF (von Willebrand factor) multimers, 3 had reduced plasma and platelet VWF levels, and none showed PFA100 closure. Two patients (those with most multimers missing) also had a short VWF half-life. Genetic analyses on the 3 patients with reduced platelet VWF levels revealed that one carried both the c.1164C>G and the c.7880G>A mutations, and another carried the c.3390C>T mutation, while the third had one of the 2 VWF alleles relatively less expressed than the other (25% versus 75%). No genetic alterations emerged in the other 2 patients. Successful replacement of the stenotic aortic valve, performed in the 2 patients with VWF mutations, did not correct their abnormal VWF multimer picture—unlike what happened in the aortic stenosis patients without bleeding symptoms.

Conclusions:
Our findings suggest that acquired von Willebrand syndrome can develop in patients with hitherto-undiagnosed inherited von Willebrand disease. Since von Willebrand disease is the most common bleeding disorder, this possibility should be considered in aortic stenosis patients—especially those with a more severe bleeding history and more disrupted VWF laboratory patterns—because they risk hemorrhage during aortic valve replacement.
Pathological Conversion of Mouse Perivascular Adipose Tissue by Notch Activation
Authors: Boucher Joshua M. , Ryzhova Larisa , Harrington Anne , Davis-Knowlton Jessica , Turner Jacqueline E. , Cooper Emily , Maridas David , Ryzhov Sergey , Rosen Clifford J. , Vary Calvin P.H. , Liaw Lucy 
Published: July 2020

Objective:
Perivascular adipose tissue (PVAT) surrounding arteries supports healthy vascular function. During obesity, PVAT loses its vasoprotective effect. We study pathological conversion of PVAT, which involves molecular changes in protein profiles and functional changes in adipocytes.

Approach and Results:
C57BL6/J mice were fed a 60% high-fat diet for 12 weeks or a cardioprotective 30% calorie-restricted diet for 5 weeks. Proteomic analysis identified PVAT as a molecularly distinct adipose depot, and novel markers for thermogenic adipocytes, such as GRP75 (stress-70 protein, mitochondrial), were identified. High-fat diet increased the similarity of protein signatures in PVAT and brown adipose, suggesting activation of a conserved whitening pathway. The whitening phenotype was characterized by suppression of UCP1 (uncoupling protein 1) and increased lipid deposition, leptin, and inflammation, and specifically in PVAT, elevated Notch signaling. Conversely, PVAT from calorie-restricted mice had decreased Notch signaling and less lipid. Using the Adipoq-Cre strain, we constitutively activated Notch1 signaling in adipocytes, which phenocopied the changes in PVAT caused by a high-fat diet, even on a standard diet. Preadipocytes from mouse PVAT expressed Sca1, CD140a, Notch1, and Notch2, but not CD105, showing differences compared with preadipocytes from other depots. Inhibition of Notch signaling during differentiation of PVAT-derived preadipocytes reduced lipid deposition and adipocyte marker expression.

Conclusions:
PVAT shares features with other adipose depots, but has a unique protein signature that is regulated by dietary stress. Increased Notch signaling in PVAT is sufficient to initiate the pathological conversion of PVAT by promoting adipogenesis and lipid accumulation and may thus prime the microenvironment for vascular disease.
Sustained Increases in Immune Transcripts and Immune Cell Trafficking During the Recovery of Experimental Brain Ischemia
Authors: Fury Wen , Park Keun Woo , Wu Zhuhao , Kim Eunhee , Woo Moon-sook , Bai Yu , Macdonald Lynn E. , Croll Susan D. , Cho Sunghee 
Published: July 2020

Background and Purpose:
Stroke is a major cause of chronic neurological disability. There is considerable interest in understanding how acute transcriptome changes evolve into subacute and chronic patterns that facilitate or limit spontaneous recovery. Here we mapped longitudinal changes in gene expression at multiple time points after stroke in mice out to 6 months.

Methods:

Adult C57BL/6 mice were subjected to transient middle cerebral artery occlusion. Longitudinal transcriptome levels were measured at 10 time points after stroke from acute to recovery phases of ischemic stroke. Localization and the number of mononuclear phagocytes were determined in the postischemic brain. Whole-mount brain imaging was performed in asplenic mice receiving GFP
+
(green fluorescent protein)-tagged splenocytes.

Results:
Sustained stroke-induced mRNA abundance changes were observed in both hemispheres with 2989 ipsilateral and 822 contralateral genes significantly perturbed. In the hemisphere ipsilateral to the infarct, genes associated with immune functions were strongly affected, including temporally overlapping innate and adaptive immunity and macrophage M1 and M2 phenotype-related genes. The strong immune gene activation was accompanied by the sustained infiltration of peripheral immune cells at acute, subacute, and recovery stages of stroke. The infiltrated immune cells were found in the infarcted area but also in remote regions at 2 months after stroke.

Conclusions:
The study identifies that immune components are the predominant molecular signatures and they may propagate or continuously respond to brain injury in the subacute to chronic phase after central nervous system injury. The study suggests a potential immune-based strategy to modify injury progression and tissue remodeling in ischemic stroke, even months after the initiating event.
Noradrenergic Regulation of Cognitive Flexibility: No Effects of Stress, Transcutaneous Vagus Nerve Stimulation, and Atomoxetine on Task-switching in Humans
Authors: Tona Klodiana-Daphne , Revers Hans , Verkuil Bart , Nieuwenhuis Sander 
Published: July 2020

Abstract
Cognitive flexibility allows us to adaptively switch between different responsibilities in important domains of our daily life. Previous work has elucidated the neurochemical basis underlying the ability to switch responses to a previously nonreinforced exemplar and to switch between attentional sets. However, the role of neuromodulators in task switching, the ability to rapidly switch between two or more cognitive tasks afforded by the same stimuli, is still poorly understood. We attempted to fill this gap by manipulating norepinephrine levels using stress manipulation (Study 1a, n = 48; between-group design), transcutaneous vagus nerve stimulation at two different intensities (Study 1b, n = 48; sham-controlled between-group design), and pharmacological manipulation (Study 2, n = 24; double-blind crossover design), all of which increased salivary cortisol measures. Participants repeatedly switched between two cognitive tasks (classifying a digit as high/low [Task 1] or as odd/even [Task 2]), depending on the preceding cue. On each trial, a cue indicated the task to be performed. The cue–stimulus interval was varied to manipulate the time to prepare for the switch. Participants showed typical switch costs, which decreased with the time available for preparation. None of the manipulations modulated the size of the switch costs or the preparation effect, as supported by frequentist and Bayesian model comparisons. Task-switching performance reflects a complex mix of cognitive control and bottom–up dynamics of task-set representations. Our findings suggest that norepinephrine does not affect either of these aspects of cognitive flexibility.
Structures and Northward Propagation of the Quasi-Biweekly Oscillation in the Western North Pacific
Authors: Li Kuiping , Yang Yang , Feng Lin , Yu Weidong , Liu Shouhua 
Published: July 2020

AbstractThis study investigates the northward-propagating quasi-biweekly oscillation (QBWO) in the western North Pacific by examining the composite meridional structures. Using newly released reanalysis and remote sensing data, the northward propagation is understood in terms of the meridional contrasts in the planetary boundary layer (PBL) moisture and the column-integrated moist static energy (MSE). The meridional contrast in the PBL moisture, with larger values north of the convection center, is predominantly attributed to the moisture convergence associated with barotropic vorticity anomalies. A secondary contribution comes from the meridional moisture advection, for which advections by mean and perturbation winds are almost equally important. The meridional contrast in the MSE tendency, due to the recharge in the front of convection and discharge in the rear of convection, is jointly contributed by the meridional and vertical MSE advections. The meridional MSE advection mainly depends on the moisture processes particularly in the PBL, and the vertical MSE advection largely results from the advection of the mean MSE by vertical velocity anomalies, wherein the upper-troposphere ascending motion related to the stratiform heating in the rear of the convection plays the major role. In addition, partial feedback from sea surface temperature (SST) anomalies is evaluated on the basis of MSE budget analysis. SST anomalies tend to enhance the surface turbulent heat fluxes ahead of the convention center and suppress them behind the convention center, thus positively contributing approximately 20% of the meridional contrast in the MSE tendency.
Reproducibility of radiomics features derived from intravoxel incoherent motion diffusion-weighted MRI of cervical cancer
Authors: Chen Hao , He Yaoyao , Zhao Cecheng , Zheng Lili , Pan Ning , Qiu Jianfeng , Zhang Zhaoxi , Niu Xiaohui , Yuan Zilong 
Published: July 2020

Background The reproducibility of intravoxel incoherent motion (IVIM)-based radiomics studies in humans has not been reported. Purpose To determine the inter- and intra-observer variability on the reproducibility of IVIM-based radiomics features in cervical cancer (CC). Material and Methods The IVIM images of 25 patients with CC were retrospectively collected. Based on the high-resolution T2-weighted images, the regions of interest (ROIs) were independently delineated twice in diffusion-weighted images at a b value of 1000 s/mm2 (interval time was one month) by two radiologists. This was done at the largest transversal cross-sections of the tumors. The ROI was subsequently used in apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f) maps derived from IVIM images. In total, 105 radiomics features were then finally extracted from the IVIM-derived maps. The inter- and intra-observer reproducibility of IVIM-derived features was then evaluated using the intraclass correlation coefficient. Results Inter- and intra-observer variability affected the reproducibility of radiomics features. D* map had 100% and 95% reproducible features, ADC map had 89% and 93%, D map had 97% and 86%, while f map had 54% and 62% reproducible features with good to excellent reliability in the intra-observer analysis. Similarly, D* map had 90% and 94%, ADC map had 85% and 70%, D map had 81% and 78%, while f map had 41% and 93% reproducible features with good to excellent reliability in the inter-observer analysis. Conclusion Inter- and intra-observer variability can affect radiomics analysis. Cognizant to this, multicenter studies should pay more attention to intra- and inter-observer variability.
Osteoarthritis of the hip: are degenerative tears of the acetabular labrum predictable from features on hip radiographs?
Authors: Gonzalez Felix M , Gagnon Marie-Helene , Reiter David , Younan Yara , Sayyid Samia , Singer Adam , Umpierrez Monica , Sharma Gulshan B , Robertson Douglas D 
Published: July 2020

Background A common feature of hip arthritis is the presence of labra tears. Recent literature suggests against the use of magnetic resonance imaging (MRI) in patients aged >45 years for the assessment of hip pain related to arthritis. Purpose To determine if radiographic features of osteoarthritis detectable on routine hip radiographs are accurate and reliable surrogate markers of degenerative acetabular labral tears identified on MR arthrography (MRA) and corroborated during arthroscopy. Material and Methods A retrospective study involving 86 symptomatic patients (hip pain) with radiologic work-up included MRA and pelvic or hip radiographs that underwent hip arthroscopy within three months. Imaging characteristics assessed on hip radiographs include measurements of superior acetabular, femoral head osteophyte, cortical thickness of the femoral shaft, and minimum joint space as well as presence of subchondral sclerosis of the femoral head and acetabulum, femoral shaft buttressing, and grade of arthritis. Presence of a labral tear was determined by consensus between three readers as well as by surgical correlation. The Pearson’s chi-squared and Fisher’s exact tests were used to compare presence of labral tears with each radiographic feature. Results Seventy-one patients (82.6%) had labral tears: 49 (69%) women and 22 (31%) men. Receiver operating characteristic analysis showed statistical significance ( P<0.05) between presence of a labral tear and acetabular and femoral head osteophyte sizes but failed to demonstrate any significance regarding acetabular subchondral sclerosis, cortical thickness, buttressing, or minimum joint space. Conclusions Radiographic markers such as the acetabular and femoral head osteophyte sizes demonstrated statistical significance with the presence of labral tears.
Risk factors and fraction of exhaled nitric oxide in obstructive sleep apnea in adults
Authors: Feng Xiaokai , Guo Xiheng , Lin Junling , Zhao Zhiling , Tong Zhaohui 
Published: July 2020

Objective This study aimed to evaluate the relationship between obstructive sleep apnea (OSA) and the fraction of exhaled nitric oxide (FENO), and to assess the effect of risk factors of airway inflammation on OSA. Methods Medical records of patients in the Respiratory Sleep Center at Chao-Yang Hospital in Beijing between January 2015 and June 2017 were analyzed. All patients were diagnosed with OSA. Data of the medical history, clinical examinations, FENO, and upper airway computed tomographic findings were collected. Logistic regression was used to evaluate risk factors of OSA. Results A total of 181 patients were admitted to the Respiratory Sleep Center during the study and 170 had a diagnosis of OSA and were included in the study. Single factor analysis showed that male sex, age, body mass index, smoking index, alcohol consumption, FENO, soft palate thickness, soft palate length, the narrowest transverse diameter of the upper airway, tonsil size, and nasal sinusitis were risk factors for sleep-disordered breathing and disease severity. Conclusions Male sex, age, body mass index, FENO, the narrowest transverse diameter of the upper airway, and normal tonsil size are associated with OSA and disease severity. The severity of OSA is associated with FENO levels.
Predictive value on diffusion weighted imaging scores for basilar artery occlusion after endovascular treatment
Authors: Wan Can , Wu Guangliang , Jin Xing , Liao Shaojun , Zhang Foming , Hu Mingzhe , Meng Miaomiao , Guo Yixin , You Jinsong 
Published: July 2020

Purpose To assess the predictive value of three scoring systems based on diffusion weighted imaging in basilar artery occlusion patients after endovascular treatment. Methods We analyzed clinical and radiological data of patients with basilar artery occlusion from January 2010 to June 2019, with modified Rankin Scale of 0–2 and 3–6 defined as favorable outcome and unfavorable outcome at three months. Diffusion weighted imaging posterior circulation ASPECTS Score (DWI pc-ASPECT Score), Renard diffusion weighted imaging Score, and diffusion weighted imaging Brainstem Score were used to evaluate the early ischemic changes. Results There were a total of 88 basilar artery occlusion patients enrolled in the study after endovascular treatment, with 33 of them getting a favorable outcome. According to the analysis, the time from onset to puncture within 12 h (odds ratio: 4.34; 95% confidence interval: 1.55–12.16; P = 0.01), presence of collateral flow via PCoA (odds ratio: 0.31; 95%CI: 0.12–0.79; P = 0.01) or between PICA and SCA (odds ratio: 0.18; 95%CI: 0.07–0.47; P = 0.00), equal or less than 15 points on baseline NIHSS (area under the curve 0.79, 95% CI 0.69–0.89; sensitivity = 69.1%, specificity = 81.8%; P = 0.00), and equal or less than 1.5 points on diffusion weighted imaging Renard score (area under the curve 0.63, 95% CI 0.51–0.75; sensitivity = 83.6%, specificity = 39.4%; P = 0.046) were independently associated with favorable outcome. Conclusions Renard diffusion weighted imaging score may be an independent predictor of functional outcome in basilar artery occlusion patients after endovascular treatment.
External training load and the effects on training response following three different training sessions in young elite beach volleyball players
Authors: Pelzer Thiemo , Schmidt Marcus , Jaitner Thomas , Pfeiffer Mark 
Published: July 2020

Purpose The interaction between external training load (ETL) and players internal response in beach volleyball is currently poor investigated. Using single parameters (e.g. jump volume) described in indoor settings is questionable due to specific load characteristics like sandy ground and reduced number of players. The aim of this work is to analyze ETL and the effects on training response in different beach volleyball training settings. Methods This study was conducted with 7 youth elite athletes (age: 18.9 ± 1.3 years, height: 185.2 ± 7 cm, body mass: 75.9 ± 10.4 kg, 2 males/5 females). Training sessions were classified into three categories with (A) high session jump volume (SJV) and lower proportions of other action types like diving, reception, defense actions and setting, (B) moderate SJV and (C) low SJV and higher proportions of other action types. Delayed Onset of Muscle Soreness [DOMS], Creatinkinase [CK] and session rate of perceived exertion [s-RPE] were analyzed as training response markers. Results Mean pre to post differences in CMJ-Height were highest at sessions with high jump volume and less other actions (Session A) with no significant differences between (C) to (B) ( p = .128), (C) to (A) ( p = .237) and (B) to (A) ( p = .101). Response markers (DOMS, s-RPE, CK) showed increased values at session type C. Conclusions SJV does not seem to trigger training response with higher marker responsiveness during low frequency sessions. Changes in directions, diving or fast getting up might rather provoke fatigue during training.
The clinical value of suPAR in diagnosis and prediction for patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis
Authors: Huang Qiangru , Xiong Huaiyu , Shuai Tiankui , Wang Yalei , Zhang Chuchu , Zhang Meng , Zhu Lei , Lu Jiaju , Liu Jian 
Published: July 2020

Background: Soluble urokinase-type plasminogen activator receptor (suPAR) is positively correlated with immune system activity. Inflammation can promote the development of chronic obstructive pulmonary disease (COPD). Therefore, this study conducted a systematic review and meta-analysis to assess the association between suPAR levels and the pathogenesis of COPD, and further assess the exact clinical value of suPAR in COPD. Methods: PubMed, Excerpt Medica Database (Embase), Web of Science (WOS), and Cochrane Library databases were searched for studies that reported the value of suPAR diagnosis for adult COPD patients. Results: A total of 11 studies were included, involving 4520 participants. Both COPD patients with predicted forced expiratory volume in 1 s (FEV1)⩾80% [weighted mean difference (WMD) = 320.25; 95% confidence interval (CI): 99.79–540.71] and FEV1 < 80% (WMD = 2950.74; 95% CI: 2647.06–3254.43) showed higher suPAR level. The sensitivity and specificity of suPAR for diagnosis of COPD were 87% and 79%, respectively, and AUC was 84%. This can not only effectively identify acute exacerbation of COPD (AECOPD) in a healthy population (WMD = 3114.77; 95% CI: 2814.66–3414.88), but also has the potential to distinguish AECOPD from stable COPD (WMD = 351.40; 95% CI: 215.88–486.93). There was a significant decrease of suPAR level after treatment [WMD = –1226.97; 95% CI: –1380.91– (–1073.03)]. Conclusion: suPAR as a novel biomarker has potential for early diagnosis of COPD and prediction of AECOPD. There is a potential correlation between the level of suPAR and the state of COPD, which may also indicate the early state and severity of COPD. When the suPAR level of COPD patients is further increased, the risk of acute exacerbation increases and should be highly valued. This also shows potential as a measure of treatment response, and as a guide to the clinical management in COPD. The reviews of this paper are available via the supplemental material section.