bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thirty minutes of handgrip exercise potentiates flow‐mediated dilatation in response to sustained and transient shear stress stimuli to a similar extent
Authors: McPhee I. A. C. , Pyke K. E. 
Published: July 2018

New Findings
What is the central question of this study?
This study sought to determine whether enhancement of brachial artery flow‐mediated dilatation (FMD) after acute exposure to a sustained elevation in shear stress is greater when the shear stress stimulus for FMD is also sustained.

What is the main finding and its importance?
Brachial artery FMD in response to a sustained (handgrip exercise) and transient (reactive hyperaemia) shear stress stimulus was enhanced to a similar extent 10 min after a 30 min handgrip exercise intervention. This suggests that prior exposure to a sustained elevation in shear stress results in a similar acute augmentation of the ability of the endothelium to transduce sustained and transient shear stress stimuli.

AbstractBrief (30 min) exposure of the brachial artery (BA) to a sustained elevation in shear stress has been shown to potentiate subsequent BA flow‐mediated dilatation (FMD) in response to a transient shear stress stimulus [reactive hyperaemia (RH) FMD]. It is unknown whether matching the sustained shear stress exposure to a subsequent sustained shear stress stimulus for FMD [via handgrip exercise (SS‐FMD)] might enhance the potentiation of FMD. The purpose of the study, therefore, was to assess the impact of a 30 min handgrip exercise intervention‐induced elevation in shear stress on subsequent BA SS‐FMD versus RH‐FMD. Nineteen healthy men (22 ± 3 years) preformed a 30 min rhythmic handgrip exercise intervention on two experimental days. BA‐FMD was assessed using either an RH or a 6 min sustained shear stress stimulus created via handgrip exercise (order of visits counterbalanced) at three time points: pre‐intervention and 10 and 60 min post‐intervention. The FMD was assessed using duplex ultrasound. Shear stress was estimated as shear rate (SR = BA blood velocity/BA diameter). Data are mean ± SD. Both SS and RH‐FMD increased from pre‐intervention to 10 min post‐intervention [SS‐FMD (6 min average), from 0.11 ± 0.05 to 0.16 ± 0.08 mm; P = 0.008; Cohen's d = 0.66; and RH‐FMD, from 0.25 ± 0.1 to 0.32 ± 0.11 mm; P = 0.013; Cohen's d = 0.68]. The magnitude of enhancement in RH and SS‐FMD did not differ (change in RH versus SS‐FMD pre‐ versus 10 min post‐intervention, P = 0.344). These findings suggest that exposure to elevated shear stress via 30 min of handgrip exercise potentiates subsequent FMD in response to sustained and transient elevations in shear stress to a similar extent.
Water drinking enhances the gain of arterial baroreflex control of muscle sympathetic nerve activity in healthy young humans
Authors: Vianna Lauro C. , Fernandes Igor A. , Martinez Daniel G. , Teixeira André L. , Silva Bruno M. , Fadel Paul J. , Nóbrega Antonio C. L. 
Published: July 2018

New Findings
What is the central question of this study?
Water drinking increases muscle sympathetic nerve activity (MSNA), and it increases arterial blood pressure (ABP) in older populations but not in young healthy subjects. Does an increase in gain of arterial baroreflex control of MSNA contribute to maintenance of ABP after water drinking in healthy young subjects?

What is the main finding and its importance?
The gain of arterial baroreflex control of MSNA was increased and remained elevated 60 min after water drinking (500 ml) but remained unchanged after saline intake. An enhancement in gain of arterial baroreflex control of MSNA contributes to the maintenance of ABP after water drinking in young healthy subjects, probably via osmosensitive mechanisms.

AbstractWater drinking increases muscle sympathetic nerve activity (MSNA), which is accompanied by a profound pressor response in patients with impaired arterial baroreflex function and in older populations, but not in healthy young subjects. We tested the hypothesis that an enhancement in the gain of arterial baroreflex control of MSNA contributes to the maintenance of arterial blood pressure after water drinking in healthy young subjects. The MSNA, arterial blood pressure and heart rate were measured in 10 healthy men (24 ± 2 years old; mean ± SD) before and for 60 min after ingestion of 500 ml of bottled water or saline solution. Weighted linear regression analysis between MSNA and diastolic blood pressure was used to determine the gain (i.e. sensitivity) of arterial baroreflex control of MSNA. After water drinking, MSNA was significantly elevated within 15 min and remained above baseline for up to 60 min [e.g. 21 ± 10 bursts (100 heart beats)−1 mmHg−1 at baseline versus 35 ± 14 bursts (100 heart beats)−1 mmHg−1 at 30 min; P < 0.01], whereas mean arterial blood pressure (e.g. 87 ± 7 mmHg at baseline versus 89 ± 7 mmHg at 30 min; P = 0.34) and heart rate were unchanged. The arterial baroreflex–MSNA gain for bursts incidence was increased and remained elevated throughout the protocol [e.g. −2.25 ± 0.99 bursts (100 heart beats)−1 mmHg−1 at baseline versus −4.32 ± 1.53 bursts (100 heart beats)−1 mmHg−1 at 30 min; P < 0.01]. Importantly, saline intake had no effect on arterial baroreflex–MSNA gain or any neurocardiovascular variables. These findings demonstrate that water drinking enhances the gain of arterial baroreflex control of MSNA in healthy young men, which may contribute to buffering the pressor response after water drinking, probably via osmosensitive mechanisms.
Phase waves and trigger waves: emergent properties of oscillating and excitable networks in the gut
Authors: Parsons Sean P. , Huizinga Jan D. 
Published: July 2018

AbstractThe gut is enmeshed by a number of cellular networks, but there is only a limited understanding of how these networks generate the complex patterns of activity that drive gut contractile functions. Here we review two fundamental types of cell behaviour, excitable and oscillating, and the patterns that networks of such cells generate, trigger waves and phase waves, respectively. We use both the language of biophysics and the theory of nonlinear dynamics to define these behaviours and understand how they generate patterns. Based on this we look for evidence of trigger and phase waves in the gut, including some of our recent work on the small intestine.
Uncovering a critical period of synaptic imbalance during postnatal development of the rat visual cortex: role of brain‐derived neurotrophic factor
Authors: Zhang Hanmeng , Mu Lianwei , Wang Dandan , Xia Dongdong , Salmon Alexander , Liu Qiuli , Wong‐Riley Margaret T. T. 
Published: July 2018

Key points
With daily electrophysiological recordings and neurochemical analysis, we uncovered a transient period of synaptic imbalance between enhanced inhibition and suppressed excitation in rat visual cortical neurons from the end of the fourth toward the end of the fifth postnatal weeks.
The expression of brain‐derived neurotrophic factor (BDNF), which normally enhances excitation and suppresses inhibition, was down‐regulated during that time, suggesting that this may contribute to the inhibition/excitation imbalance.
An agonist of the BDNF receptor tropomyosin‐related kinase B (TrkB) partially reversed the imbalance, whereas a TrkB antagonist accentuated the imbalance during the transient period.
Monocular lid suture during the transient period is more detrimental to the function and neurochemical properties of visual cortical neurons than before or after this period.
We regard the period of synaptic imbalance as the peak critical period of vulnerability, and its existence is necessary for neurons to transition from immaturity to a more mature state of functioning.
AbstractThe mammalian visual cortex is immature at birth and undergoes postnatal structural and functional adjustments. The exact timing of the vulnerable period in rodents remains unclear. The critical period is characterized by inhibitory GABAergic maturation reportedly dependent on brain‐derived neurotrophic factor (BDNF). However, most of the studies were performed on experimental/transgenic animals, questioning the relationship in normal animals. The present study aimed to conduct in‐depth analyses of the synaptic and neurochemical development of visual cortical neurons in normal and monocularly‐deprived rats and to determine specific changes, if any, during the critical period. We found that (i) against a gradual increase in excitation and inhibition with age, a transient period of synaptic and neurochemical imbalance existed with suppressed excitation and enhanced inhibition at postnatal days 28 to 33/34; (ii) during this window, the expression of BDNF and tropomyosin‐related kinase B (TrkB) receptors decreased, along with glutamatergic GluN1 and GluA1 receptors and the metabolic marker cytochrome oxidase, whereas that of GABAARα1 receptors continued to rise; (iii) monocular deprivation reduced both excitatory and inhibitory synaptic activity and neurochemicals mainly during this period; and (iv) in vivo TrkB agonist partially reversed the synaptic imbalance in normal and monocularly‐deprived neurons during this time, whereas a TrkB antagonist accentuated the imbalance. Thus, our findings highlight a transitory period of synaptic imbalance with a negative relationship between BDNF and inhibitory GABA. This brief critical period may be necessary in transitioning from an immature to a more mature state of visual cortical functioning.
Disagreement of diameter and volume measurements for pulmonary nodule size estimation in CT lung cancer screening
Authors: Heuvelmans Marjolein A , Walter Joan E , Vliegenthart Rozemarijn , van Ooijen Peter M A , De Bock Geertruida H , de Koning Harry J , Oudkerk Matthijs 
Published: July 2018

We studied 2240 indeterminate solid nodules (volume 50–500mm3) to determine the correlation of diameter and semi-automated volume measurements for pulmonary nodule size estimation. Intra-nodular diameter variation, defined as maximum minus minimum diameter through the nodule’s center, varied by 2.8 mm (median, IQR:2.2–3.7 mm), so above the 1.5 mm cutoff for nodule growth used in Lung CT Screening Reporting and Data System (Lung-RADS). Using mean or maximum axial diameter to assess nodule volume led to a substantial mean overestimation of nodule volume of 47.2% and 85.1%, respectively, compared to semi-automated volume. Thus, size of indeterminate nodules is poorly represented by diameter.Trial registration numberPre-results, ISRCTN63545820.
Characteristics of new solid nodules detected in incidence screening rounds of low-dose CT lung cancer screening: the NELSON study
Authors: Walter Joan E , Heuvelmans Marjolein A , Bock Geertruida H de , Yousaf-Khan Uraujh , Groen Harry J M , Aalst Carlijn M van der , Nackaerts Kristiaan , Ooijen Peter M A van , Koning Harry J de , Vliegenthart Rozemarijn , Oudkerk Matthijs 
Published: July 2018

PurposeNew nodules after baseline are regularly found in low-dose CT lung cancer screening and have a high lung cancer probability. It is unknown whether morphological and location characteristics can improve new nodule risk stratification by size.MethodsSolid non-calcified nodules detected during incidence screening rounds of the randomised controlled Dutch-Belgian lung cancer screening (NELSON) trial and registered as new or previously below detection limit (15 mm3) were included. A multivariate logistic regression analysis with lung cancer as outcome was performed, including previously established volume cut-offs (<30 mm3, 30–<200 mm3 and ≥200 mm3) and nodule characteristics (location, distribution, shape, margin and visibility <15 mm3 in retrospect).ResultsOverall, 1280 new nodules were included with 73 (6%) being lung cancer. Of nodules ≥30 mm3 at detection and visible <15 mm3 in retrospect, 22% (6/27) were lung cancer. Discrimination based on volume cut-offs (area under the receiver operating characteristic curve (AUC): 0.80, 95% CI 0.75 to 0.84) and continuous volume (AUC: 0.82, 95% CI 0.77 to 0.87) was similar. After adjustment for volume cut-offs, only location in the right upper lobe (OR 2.0, P=0.012), central distribution (OR 2.4, P=0.001) and visibility <15 mm3 in retrospect (OR 4.7, P=0.003) remained significant predictors for lung cancer. The Hosmer-Lemeshow test (P=0.75) and assessment of bootstrap calibration curves indicated adequate model fit. Discrimination based on the continuous model probability (AUC: 0.85, 95% CI 0.81 to 0.89) was superior to volume cut-offs alone, but when stratified into three risk groups (AUC: 0.82, 95% CI 0.78 to 0.86), discrimination was similar.ConclusionContrary to morphological nodule characteristics, growth-independent characteristics may further improve volume-based new nodule lung cancer prediction, but in a three-category stratification approach, this is limited.Trial registration numberISRCTN63545820; pre-results.
Single-buried-layer reflection-mode metasurfaces for dual-band linear to circular polarization conversion
Authors: Fartookzadeh Mahdi 
Published: July 2018

In this paper, analysis, design and simulation of dual-band metasurfaces as the reflection-mode linear to circular polarization converters (RMCPs) consisting of single-buried-layer rectangular patches are carried out. The proposed structure for RMCPs can be realized for all frequency ranges from microwave to optical frequencies. However, two far-infrared frequencies, 2 THz and 10 THz, are considered for the design. Dimensions of the dual-band RMCP are obtained using equivalent transmission line circuit and defining a circular polarization (CP) indicator factor (RLI), which should be about ±[Formula: see text]1 for CP. An advantage of the proposed RMCP is the wide permitted angle of incidence [Formula: see text] in both operating frequencies. Simulation results of the proposed RMCP indicate 41.2% and 39.1% bandwidths for 3-dB axial ratio (AR) at 2 THz and 10 THz, respectively with [Formula: see text] and [Formula: see text]. In addition, higher quality of CP can be obtained by reducing the incident angle difference. For example, 2-dB AR bandwidths of the proposed metasurface are 28.4% and 42.1% at 2 THz and 10 THz, respectively, with [Formula: see text] and [Formula: see text].
Seismic and lithofacies characterization of a gravity core transect down the submarine Tuaheni Landslide Complex, NE New Zealand
Authors: Kuhlmann Jannis , Orpin Alan R. , Mountjoy Joshu J. , Crutchley Gareth J. , Henrys Stuart , Lunenburg Ryan , Huhn Katrin 
Published: July 2018

Abstract
The southern Tuaheni Landslide Complex (TLC) at the Hikurangi subduction margin displays distinctive morphological features along its distribution over the Tuaheni slope offshore Gisborne, New Zealand. We here present first analyses of a gravity core transect that systematically samples surficial sediments from the source area to the toe of this landslide complex, thus providing important new insight into shallow lithological variation in the slide complex. Geophysical and geochemical core logs and core descriptions form the basis for a characterization of representative sediment successions that are indicative of the respective slope segment of recovery. Our results show that the lithology of surficial sediments varies significantly along the length of the landslide complex. Depending on the slope segment observed, this variation includes post-Last Glacial Maximum (LGM) outer-shelf sediments, and hemipelagic drape and near-surface reworked debris avalanche deposits, as well as multiple intercalated thinner turbidites and tephra layers at the distal end of the profile. Lithological downslope variability suggests ongoing mass transport events through the late Holocene that were likely to have been limited to small mud-turbidite flows. Integration with acoustic sub-bottom imagery reveals the presence of multiple stacked mass-transport deposits at depth, contrasting with previous interpretations of a single parent failure.
Canonical Wnt Signaling Remodels Lipid Metabolism in Zebrafish Hepatocytes following Ras Oncogenic Insult
Authors: Yao Yuxiao , Sun Shaoyang , Wang Jingjing , Fei Fei , Dong Zhaoru , Ke Ai-Wu , He Ruoyu , Wang Lei , Zhang Lili , Ji Min-Biao , Li Qiang , Yu Min , Shi Guo-Ming , Fan Jia , Gong Zhiyuan , Wang Xu 
Published: July 2018

Abstract
There is limited understanding of the effects of major oncogenic pathways and their combinatorial actions on lipid composition and transformation during hepatic tumorigenesis. Here, we report a negative correlation of Wnt/Myc activity with steatosis in human hepatocellular carcinoma (HCC) and perform in vivo functional studies using three conditional transgenic zebrafish models. Double-transgenic zebrafish larvae conditionally expressing human CTNNB1mt and zebrafish tcf7l2 or murine Myc together with krasv12 in hepatocytes led to severe hepatomegaly and significantly attenuated accumulation of lipid droplets and cell senescence triggered by krasv12 expression alone. UPLC-MS–based, nontargeted lipidomic profiling and transcriptome analyses revealed that Wnt/Myc activity promotes triacylglycerol to phospholipid transformation and increases unsaturated fatty acyl groups in phospholipids in a Ras-dependent manner. Small-scale screenings suggested that supplementation of certain free fatty acids (FA) or inhibition of FA desaturation significantly represses hepatic hyperplasia of double-transgenic larvae and proliferation of three human HCC cells with and without sorafenib. Together, our studies reveal novel Ras-dependent functions of Wnt signaling in remodeling the lipid metabolism of cancerous hepatocytes in zebrafish and identify the SCD inhibitor MK8245 as a candidate drug for therapeutic intervention.
Significance: These findings identify FA desaturation as a significant downstream therapeutic target for antagonizing the combinatorial effects of Wnt and Ras signaling pathways in hepatocellular carcinoma.
Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/19/5548/F1.large.jpg. Cancer Res; 78(19); 5548–60. ©2018 AACR.
Antitumor Activity of MEDI3726 (ADCT-401), a Pyrrolobenzodiazepine Antibody–Drug Conjugate Targeting PSMA, in Preclinical Models of Prostate Cancer
Authors: Cho Song , Zammarchi Francesca , Williams David G. , Havenith Carin E.G. , Monks Noel R. , Tyrer Peter , D'Hooge Francois , Fleming Ryan , Vashisht Kapil , Dimasi Nazzareno , Bertelli Francois , Corbett Simon , Adams Lauren , Reinert Halla W. , Dissanayake Sandamali , Britten Charles E. , King Wanda , Dacosta Karma , Tammali Ravinder , Schifferli Kevin , Strout Patrick , Korade Martin , Masson Hinrichs Mary Jane , Chivers Simon , Corey Eva , Liu He , Kim Sae , Bander Neil H. , Howard Philip W. , Hartley John A. , Coats Steve , Tice David A. , Herbst Ronald , van Berkel Patrick H. 
Published: July 2018

Abstract
Prostate-specific membrane antigen (PSMA) is a membrane-bound glutamate carboxypeptidase that is highly expressed in nearly all prostate cancers with the highest expression in metastatic castration-resistant prostate cancer (mCRPC). The prevalence of increased surface expression and constitutive internalization of PSMA make it an attractive target for an antibody–drug conjugate (ADC) approach to treating patients with mCRPC. MEDI3726 (previously known as ADCT-401) is an ADC consisting of an engineered version of the anti-PSMA antibody J591 site specifically conjugated to the pyrrolobenzodiazepine (PBD) dimer tesirine. MEDI3726 specifically binds the extracellular domain of PSMA and, once internalized, releases the PBD dimer to crosslink DNA and trigger cell death. In vitro, MEDI3726 demonstrated potent and specific cytotoxicity in a panel of PSMA-positive prostate cancer cell lines, consistent with internalization and DNA interstrand crosslinking. In vivo, MEDI3726 showed robust antitumor activity against the LNCaP and the castration-resistant CWR22Rv1 prostate cancer cell line xenografts. MEDI3726 also demonstrated durable antitumor activity in the PSMA-positive human prostate cancer patient–derived xenograft (PDX) LuCaP models. This activity correlated with increased phosphorylated Histone H2AX in tumor xenografts treated with MEDI3726. MEDI3726 is being evaluated in a phase I clinical trial as a treatment for patients with metastatic castrate-resistant prostate cancer (NCT02991911). Mol Cancer Ther; 17(10); 2176–86. ©2018 AACR.
The Role of Serum Caspase 3 Levels in Prediction of Endometriosis Severity
Authors: Kaya Cihan , Alay Ismail , Guraslan Hakan , Gedikbasi Asuman , Ekin Murat , Ertaş Kaya Sinem , Oral Engin , Yasar Levent 
Published: August 2018

<b><i>Background/Aims:</i></b> To identify the role of serum caspase 3, Annexin A2 (ANXA2), and Soluble Fas Ligand (sFasL) levels in the prediction of endometriosis severity. <b><i>Methods:</i></b> The study was performed on 90 women who were candidates for laparoscopic surgery due to endometrioma or any other benign ovarian cysts detected by ultrasound examination, pelvic pain, or infertility. The control group comprised 29 patients. The second group comprised 29 patients with stage I–II endometriosis and the third group comprised 30 patients with stage III–IV endometriosis. <b><i>Results:</i></b> Significant differences were detected between the control and stage III–IV endometriosis groups and between stage I–II and stage III–IV endometriosis groups in terms of caspase-3 levels (both, <i>p</i> &#x3c; 0.001), ANXA2 levels (<i>p</i> = 0.007 and <i>p</i> = 0.002), and sFasL levels (<i>p</i> = 0.022 and <i>p</i> = 0.044). After receiver operating characteristic analysis, the area under curve was 93% (95% CI 57–82) at 10.7 ng/mL cut-off level for caspase-3 with 90% sensitivity and 87% specificity. <b><i>Conclusion:</i></b> Serum caspase-3 level may be a reliable predictor of endometriosis severity.