bluuebunny/crossref_metadata_2025 huggingface dataset:
Requesting here-and-now actions with two imperative formats in Korean
interaction
Authors: Kim Stephanie Hyeri , Kim Mary Shin
Published: April 2020

This chapter analyzes two Korean imperative formats, the
-e/a imperative and the imperative formed with the
auxiliary verb po‑ ‘see’ (referred to as the plain imperative and the pwa imperative, respectively), focusing on the requests of
here-and-now actions. Pwa imperatives are selected when the
nominated action is a step that advances the larger course of action in
progress and anticipates a next action, although the outcome of the
nominated action is only provisionally determined. Plain imperatives, on the
other hand, are deployed when no further actions are suggested as part of
the nominated action. The paper challenges the previous explanations based on social
distance or politeness by showing that the selection of the imperatives hinges on a particular
‘situation design’, that is, whether the nominated action is connected to
the larger action trajectory.
Linguistic structures emerging in the synchronization of a Pilates
class
Authors: Keevallik Leelo
Published: April 2020

This chapter targets grammar in the interactive process
between a Pilates teacher and the exercising students, an activity context
in which instruction and compliance can be designed to merge in time. It
shows how linguistic structure, such as counts, formula, and phrases,
emerges step-by-step sensitively to the others’ currently moving bodies. At
the same time, the situation-designed structures direct the students through
the partially known moves. In contrast to formal theories that consider
grammar as a device for coherent expression of propositions, this study
argues that grammatical structure emerges through recurrent use in a
specific activity context. The video-recorded data is in Estonian.
Multimodal mechanisms for mobilizing students to give pre-structured
responses in French L2 classroom interaction
Authors: Chazal Kirby
Published: April 2020

This study examines interactions in French L2 university
classroom discourse from a multimodal conversation analytic (CA)
perspective. In these interactions, a teacher mobilizes students to respond,
then evaluates and subsequently reveals their responses on digital slides as
a ratification of correct responses. As the co-participants build a joint
interactional history with this task, the teacher becomes increasingly more
reliant on embodied orientations toward the computer displaying the slides,
thereby helping to both manage and transition between sequences of
interaction. The findings provide insights into how the multimodal
management of pedagogical artifacts, such as digital slides, can work to
mobilize, evaluate and create interactional space for students to respond in
teacher-led interaction.
Excellent electronic transport in heterostructures of graphene and monoisotopic boron-nitride grown at atmospheric pressure
Authors: Sonntag J , Li J , Plaud A , Loiseau A , Barjon J , Edgar J H , Stampfer C
Published: April 2020

Hexagonal boron nitride (BN), one of the very few layered insulators, plays a crucial role in 2D materials research. In particular, BN grown with a high pressure technique has proven to be an excellent substrate material for graphene and related 2D materials, but at the same time very hard to replace. Here we report on a method of growth at atmospheric pressure as a true alternative for producing BN for high quality graphene/BN heterostructures. The process is not only more scalable, but also allows to grow isotopically purified BN crystals. We employ Raman spectroscopy, cathodoluminescence, and electronic transport measurements to show the high-quality of such monoisotopic BN and its potential for graphene-based heterostructures. The excellent electronic performance of our heterostructures is demonstrated by well developed fractional quantum Hall states, ballistic transport over distances around 10 µm at low temperatures and electron-phonon scattering limited transport at room temperature.
Instrument suite cost optimisation in a science megaproject
Authors: Bentley Phillip M
Published: April 2020

This article presents a cost optimisation study of neutron scattering instrumentation at the European Spallation Source (ESS) in Lund, Sweden. This is done by focusing on the main cost drivers for almost half of the instrument hardware—optics and shielding —and trading detailed cost functions against beam transmission functions in a multi-dimensional, yet simple, parameter space. A cost saving of almost 30% is identified. The method is demonstrated in a worked example on a mature instrument design, and there are no reductions in performance. The proposed solution is shown to correspond to a Nash equilibrium of simultaneous shielding and optics strategies, versus the baseline which is trapped by working through sequential strategies. Finally, this cost analysis is bench-marked against, and found to be in agreement with, the costs of operational facilities of a similar class.
Atomic resolution enabled STEM imaging of nanocrystals at cryogenic temperature
Authors: Tyukalova Elizaveta , Duchamp Martial
Published: April 2020

In this study, we address the problem of electron-beam induced damage on two energy-related materials: LiNi0.5Mn1.5O4 used as a cathode material for lithium-ion batteries and ZnCo1.8Ni0.2O4 used as a catalyst for oxygen evolution reaction. Both materials were found to transform from the spinel into the rocksalt phase while being imaged by high-resolution scanning transmission electron microscopy (HR-STEM) at room temperature. To mitigate the degradation, we found HR-STEM characterization at cryogenic temperature delays the critical electron dose for structural modification. We determined the native phase of materials to be spinel while the other phases observed by HR-STEM were induced by the electron-beam. From a careful analysis of the experimental data and a detailed understanding of the different degradation processes induced by an energetic electron beam, we conclude that radiolysis is the mechanism responsible for the degradation in LiNi0.5Mn1.5O4 and ZnCo1.8Ni0.2O4 nanoparticles.
Overview of cell motility-based sickle cell disease diagnostic system in shearing digital holographic microscopy
Authors: O’Connor Timothy , Anand Arun , Andemariam Biree , Javidi Bahram
Published: April 2020

We overview a previously reported low-cost, compact, and 3D-printed shearing interferometer system for automated diagnosis of sickle cell disease based on red blood cell (RBC) bio-physical parameters and membrane fluctuations measured via digital holographic microscopy. The portable quantitative phase microscope is used to distinguish between healthy RBCs and those affected by sickle cell disease. Video holograms of RBCs are recorded, then each video hologram frame is computationally reconstructed to retrieve the time-varying phase profile of the cell distribution under study. The dynamic behavior of the cells is captured by creating a spatio-temporal data cube from which features regarding membrane fluctuations are extracted. Furthermore, the Optical Flow algorithm was used to capture lateral motility information of the cells. The motility-based features are combined with physical, morphology-based cell features and inputted into a random forest classifier which outputs the health state of the cell. Classification is performed with high accuracy at both the cell level and patient level.
Vortex arrays directly generated from an efficient diode-pumped microchip laser
Authors: Chen Dimeng , Miao Yujie , Wang Hanjie , Dong Jun
Published: April 2020

Optical vortex arrays with multiple singularities arranged in distinct lattice structures provide more flexibility in trapping or manipulating microparticles, large-capacity optical communications and high-security information processing, and optical modulation. An efficient high-power compact laser with singularity-tunable vortex-array distribution is crucial for practical applications. Here, we directly generate various vortex arrays with tunable singularities from 1 to 10 in a microchip laser pumped with a tilted annular beam. Formation of vortex arrays in the microchip laser is achieved by manipulating the gain distribution in an Yb:YAG crystal by controlling the tilt angles and pump power. Efficient high-power laser operation with output power of 2.01 W and optical efficiency of 24.5% is obtained for a vortex array with 10 singularities. The pump-power-dependent saturated population inversion distribution plays a key role in generating vortex arrays formed with multi-transverse modes oscillating simultaneously in transverse-mode locking. The good agreement between theoretically simulated transverse patterns, phases and interference patterns for the vortex arrays and experimentally obtained results provides a solid foundation for developing efficient compact microchip lasers for generating vortex arrays by manipulating gain distribution in a thin medium pumped with a tilted annular beam.
Asbestos Exposure of Chrysotile Miners and Millers in Balangero, Italy
Authors: Silvestri Stefano , Ferrante Daniela , Giovannini Andrea , Grassi Francesco , Carofalo Stefania , Ferrara Rita , Magnani Corrado , Mirabelli Dario
Published: April 2020

The largest chrysotile mine in Western Europe was active in Balangero (Italy) from 1917 to 1990. We quantitatively assessed exposure to asbestos in the framework of a cohort study on mortality of Balangero miners and millers. Using documents filed at the Italian State Archive we reconstructed the job-histories of cohort members. The concentration of asbestos fibres by work-area was derived from industrial hygiene surveys since 1968 and monitoring programs since 1975. Earlier exposures had been estimated based on the experimental reconstruction of past working conditions. In the mine concentrations of about 20 fibres per millilitre (f/ml) were initially present, decreasing to 5 in the mid-1950s and to <1 in late 1970s. In milling areas higher levels were present and did not fall below 1 f/ml until the mid-1980s. Cumulative exposure of cohort members, as the sum over their job-history of their year- and area-specific exposures, were <10 fibre/millilitre years (f/ml-y) in 18% of workers, 10–100 in 32%, 100–1000 in 37%, and >1000 in 13%. Compared with recently published estimates for the Russian chrysotile mine in Asbest, fibre concentrations in Balangero were higher during the 1950s and 1960s. Such difference may be partly accounted for by difficulties in converting dust measurements to fibre concentrations in the Russian study and the need to rely on the experimental reconstruction of exposures before 1968 in our study.
Contrasting size-dependent life history strategies of an insular lizard
Authors: Rotger Andreu , Igual José Manuel , Tavecchia Giacomo
Published: April 2020

In many species with continuous growth, body size is an important driver of life-history tactics and its relative importance is thought to reflect the spatio-temporal variability of selective pressures. We developed a deterministic size-dependent integral projection model for 3 insular neighboring lizard populations with contrasting adult body sizes to investigate how size-related selective pressures can influence lizard life-history tactics. For each population, we broke down differences in population growth rates into contributions from size-dependent body growth, survival, and fecundity. A life table response experiment (LTRE) was used to compare the population dynamics of the 3 populations and quantify the contributions of intrinsic demographic coefficients of each population to the population growth rate (λ). Perturbation analyses revealed that the largest adults contributed the most to the population growth rate, but this was not true in the population with the smallest adults and size-independent fertility. Although we were not able to identify a single factor responsible for this difference, the combination of the demographic model on a continuous trait coupled with an LTRE analysis revealed how individuals from sister populations of the same species follow different life strategies and showed different compensatory mechanisms among survival, individual body growth, and fertility. Our results indicate that body size can play a contrasting role even in closely-related and closely-spaced populations.
Adaptive development of concomitant secondary mitral and tricuspid regurgitation after transcatheter aortic valve replacement
Authors: Winter Max-Paul , Bartko Philipp E. , Krickl Annika , Gatterer Constantin , Donà Carolina , Nitsche Christian , Koschutnik Matthias , Spinka Georg , Siller-Matula Jolanta M. , Lang Irene M. , Mascherbauer Julia , Hengstenberg Christian , Goliasch Georg
Published: April 2020

Aims

Concomitant secondary atrioventricular regurgitation is frequent in patients with severe aortic stenosis scheduled for transcatheter aortic valve replacement (TAVR). The future implications of leaving associated valve lesions untreated after TAVR remain unknown. Aim of the present study was to characterize the evolution of concomitant secondary atrioventricular regurgitations and to evaluate their impact on long-term prognosis.

Methods and results

We prospectively enrolled 429 consecutive TAVR patients. All patients underwent comprehensive clinical, laboratory, and echocardiographic assessments prior to TAVR, at discharge, and yearly thereafter. All-cause mortality was chosen as primary study endpoint. At baseline, severe concomitant secondary mitral regurgitation (sMR) was present in 54 (13%) and severe concomitant secondary tricuspid regurgitation (sTR) in 75 patients (17%). After TAVR 59% of patients with severe sMR at baseline experienced sMR regression, whereas analogously sTR regressed in 43% of patients with severe sTR. Persistence of sTR and sMR were associated with excess mortality after adjustment for our bootstrap-selected confounder model with an adjusted HR of 2.44 (95% CI 1.15–5.20, P = 0.021) for sMR and of 2.09 (95% CI 1.20–3.66, P = 0.01) for sTR. Patients showing regression of atrioventricular regurgitation exhibited survival rates indistinguishable to those seen in patients without concomitant atrioventricular regurgitation (sMR: P = 0.83; sTR: P = 0.74).

Conclusion

Concomitant secondary atrioventricular regurgitation in patients with severe AS is a highly dynamic process with up to half of all patients showing regression of associated valvular regurgitation after TAVR and subsequent favourable post-interventional outcome. Persistent atrioventricular regurgitation is a major determinant of unfavourable outcome after TAVR and proposes a window of early sequel intervention.
Relating Stocking and Density for Natural Regeneration of Conifers in Northern California
Authors: Ritchie Martin W
Published: April 2020

Natural regeneration cannot be effectively evaluated by tree density because of spatial heterogeneity typically observed. A proper interpretation of natural regeneration will consider some evaluation of area stocked. However, stocking estimates for natural regeneration are plot-size-dependent. Stocking at the 1-milacre scale is not generally comparable to that on a 4-milacre scale unless a generalized relation with stand density can be established. A generalized relation was first suggested to hold in a paper by Lynch and Schumacher (1941), but this has not been confirmed in subsequent studies. The Lynch and Schumacher hypothesis of a generalized regeneration density-stocking relation across plot size was tested using observations on 60 stands. Results were consistent with Lynch and Schumacher (1941). With evidence of a well-defined relation for plots ranging from 1 to 10 milacres, it appears possible to approximate, for ponderosa pine and associated species, the natural regeneration stocking percentage for a range of stocking standards based solely on observations of regeneration density. Confidence intervals were derived for a range of stocking standards in English units from 1 to 10 milacre and for metric units from 0.0005 hectares to 0.0040 hectares.
State feedback observer-based control design for linear descriptor systems with multiple time-varying delays
Authors: Phat V N , Niamsup P , Muoi N H
Published: April 2020

In this paper, we propose an linear matrix inequality (LMI)-based design method to observer-based control problem of linear descriptor systems with multiple time-varying delays. The delay function can be continuous and bounded but not necessarily differentiable. First, by introducing a new set of improved Lyapunov–Krasovskii functionals that avoid calculating the derivative of the delay function, we obtain new delay-dependent sufficient conditions for guaranteeing the system to be regular, impulse-free and asymptotically stable. Then, based on the derived stability conditions, we design state feedback controllers and observer gains via LMIs, which can be solved numerically in standard computational algorithms. A numerical example with simulation is given to demonstrate the efficiency and validity of the proposed deign.
Representativeness of Black Patients in Cancer Clinical Trials Sponsored by the National Cancer Institute Compared With Pharmaceutical Companies
Authors: Unger Joseph M , Hershman Dawn L , Osarogiagbon Raymond U , Gothwal Anirudh , Anand Seerat , Dasari Arvind , Overman Michael , Loree Jonathan M , Raghav Kanwal
Published: April 2020

Background

Many clinical trials supporting new drug applications underrepresent minority patients. Trials conducted by the National Cancer Institute’s National Clinical Trial’s Network (NCTN) have greater outreach to community sites, potentially allowing better representation. We compared the representation of Black patients in pharmaceutical company–sponsored cancer clinical trials with NCTN trials and with the US cancer population.

Methods

We established a large cohort of study publications representing the results of trials that supported new US Food and Drug Administration drug approvals from 2008 to 2018. NCTN trial data were from the SWOG Cancer Research Network. US cancer population rates were estimated using Surveillance, Epidemiology, and End Results survey data. We compared the proportion of Black patients by enrollment year for each cancer type and overall. Tests of proportions were used. All statistical tests were 2-sided.

Results

A total 358 trials (pharmaceutical company–sponsored trials, 85; SWOG trials, 273) comprised of 93 825 patients (pharmaceutical company–sponsored trials, 46 313; SWOG trials, 47 512) for 15 cancer types were analyzed. Overall, the proportion of Black patients was 2.9% for pharmaceutical company–sponsored trials, 9.0% for SWOG trials, and 12.1% for the US cancer population (P < .001 for each pairwise comparison). These findings were generally consistent across individual cancer types.

Conclusions

The poor representation of Black patients in pharmaceutical company–sponsored trials supporting new drug applications could result in the use of new drugs with little data about efficacy or side effects in this key population. Moreover, because pharmaceutical company–sponsored trials test the newest available therapies, limited access to these trials represents a disparity in access to potential breakthrough therapies.
Transplacental Respiratory Syncytial Virus and Influenza Virus Antibody Transfer in Alaska Native and Seattle Mother–Infant Pairs
Authors: Chu Helen Y , Newman Kira L , Englund Janet A , Cho Shari , Bull Catherine , Lacombe Kirsten , Carlin Kristen , Bulkow Lisa R , Rudolph Karen , DeByle Carolynn , Berner James , Klejka Joseph , Singleton Rosalyn
Published: April 2020

Background

Alaska Native (AN) infants are at risk for severe disease due to respiratory syncytial virus (RSV) and influenza. Maternal immunization protects young infants through transplacental antibody transfer. RSV- and influenza-specific transplacental antibody transfer in mother–infant pairs has not previously been evaluated in the AN population.

Methods

Serum samples collected during pregnancy and at birth from AN mother–infant pairs in the Yukon-Kuskokwim Delta region (YKD) of Alaska (2000–2011; n = 75) and predominantly white pairs in Seattle, Washington (2014–2016; n = 57), were tested for RSV and influenza antibody using a microneutralization and hemagglutination inhibition assay, respectively, and compared between sites.

Results

Mean RSV antibody concentrations in pregnant women in YKD and Seattle were similar (log2 RSV antibody 10.6 vs 10.7, P = .86), but cord blood RSV antibody concentrations were significantly lower in infants born to mothers in YKD compared with Seattle (log2 RSV antibody 11.0 vs 12.2, P < .001). Maternal and cord blood influenza antibody concentrations were lower for women and infants in YKD compared with Seattle for all 4 influenza antigens tested (all P < .05). The mean cord to maternal RSV antibody transfer ratio was 1.15 (standard deviation [SD], 0.13) in mother–infant pairs in Seattle compared with 1.04 (SD, 0.08) in YKD. Mean cord blood to maternal antibody transfer ratios for influenza antigens ranged from 1.22 to 1.42 in Seattle and from 1.05 to 1.59 in YKD.

Conclusions

Though the transplacental antibody transfer ratio was high (>1.0) for both groups, transfer ratios for RSV antibody were significantly lower in AN mother–infant pairs. Further studies are needed to elucidate the impact of lower transplacental antibody transfer on infant disease risk in rural Alaska.

Alaska Native and continental US mother-infant pairs have high transplacental antibody transfer ratios (>1.0) for influenza and respiratory syncytial virus, but anti-respiratory syncytial virus antibody levels are significantly lower in Alaska Native pairs than in those from the continental US.
Belief, Faith, and Hope: On the Rationality of Long-Term Commitment
Authors: Jackson Elizabeth
Published: April 2020

I examine three attitudes: belief, faith, and hope. I argue that all three attitudes play the same role in rationalizing action. First, I explain two models of rational action—the decision-theory model and the belief-desire model. Both models entail there are two components of rational action: an epistemic component and a conative component. Then, using this framework, I show how belief, faith, and hope that p can all make it rational to accept, or act as if, p. I conclude by showing how my picture can explain how action-oriented commitments can be rational over time, both in the face of counterevidence and in the face of waning affections.
Perceptions of prognosis and goal of treatment in patients with malignant gliomas and their caregivers
Authors: Forst Deborah A , Quain Kit , Landay Sophia L , Anand Maya , Kaslow-Zieve Emilia , Mesa Michelle M , Jacobs Jamie M , Dietrich Jorg , Parsons Michael W , Horick Nora , Greer Joseph A , Batchelor Tracy T , Jackson Vicki A , El-Jawahri Areej , Temel Jennifer S
Published: April 2020

Background

Patients with malignant gliomas have a poor prognosis. However, little is known about patients’ and caregivers’ understanding of the prognosis and the primary treatment goal.

Methods

We conducted a prospective study in patients with newly diagnosed malignant gliomas (N = 72) and their caregivers (N = 55). At 12 weeks after diagnosis, we administered the Prognosis and Treatment Perceptions Questionnaire to assess understanding of prognosis and the Hospital Anxiety and Depression Scale to evaluate mood. We used multivariable regression analyses to explore associations between prognostic understanding and mood and McNemar tests to compare prognostic perceptions among patient-caregiver dyads (N = 48).

Results

A total of 87.1% (61/70) of patients and 79.6% (43/54) of caregivers reported that it was “very” or “extremely” important to know about the patient’s prognosis. The majority of patients (72.7%, [48/66]) reported that their cancer was curable. Patients who reported that their illness was incurable had greater depressive symptoms (B = 3.01, 95% CI, 0.89-5.14, P = .01). There was no association between caregivers’ prognostic understanding and mood. Among patient-caregiver dyads, patients were more likely than caregivers to report that their primary treatment goal was cure (43.8% [21/48] vs 25.0% [12/48], P = .04) and that the oncologist’s primary goal was cure (29.2% [14/48] vs 8.3% [4/48], P = .02).

Conclusions

Patients with malignant gliomas frequently hold inaccurate perceptions of the prognosis and treatment goal. Although caregivers more often report an accurate assessment of these metrics, many still report an overly optimistic perception of prognosis. Interventions are needed to enhance prognostic communication and to help patients cope with the associated distress.
In Full Flow: Left Ventricular Assist Device Infections in the Modern Era
Authors: Zinoviev Radoslav , Lippincott Christopher K , Keller Sara C , Gilotra Nisha A
Published: April 2020

With the rising prevalence of heart disease in the United States, there is increasing reliance on durable mechanical circulatory support (MCS) to treat patients with end-stage heart failure. Left ventricular assist devices (LVADs), the most common form of durable MCS, are implanted mechanical pumps that connect to an external power source through a transcutaneous driveline. First-generation LVADs were bulky, pulsatile pumps that were frequently complicated by infection. Second-generation LVADs have an improved design, though infection remains a common and serious complication due to the inherent nature of implanted MCS. Infections can affect any component of the LVAD, with driveline infections being the most common. LVAD infections carry significant morbidity and mortality for LVAD patients. Therefore, it is paramount for the multidisciplinary team of clinicians caring for these patients to be familiar with this complication. We review the epidemiology, prevention, diagnosis, treatment, and outcomes of LVAD infections.
Darboux transformation and multi-soliton solutions of the discrete sine-Gordon equation
Authors: Hanif Y , Saleem U
Published: April 2020

We study the discrete Darboux transformation and construct multi-soliton solutions in terms of the ratio of determinants for the integrable discrete sine-Gordon equation. We also calculate explicit expressions of single-, double-, triple-, and quadruple-soliton solutions as well as single- and double-breather solutions of the discrete sine-Gordon equation. The dynamical features of discrete kinks and breathers are also illustrated.
Evaluation of the Antidiabetic Effect of Clerodendrum volubile P. Beauv leaves: In vivo and In Silico Approach
Authors: Molehin Olorunfemi Raphael , Elekofehinti Olusola Olalekan , Oloyede Omotade Ibidun
Published: April 2020

Clerodendrum volubile leaf is commonly used in traditional medicine for the management of various diseases including diabetes in Nigeria. This study sought to propose the possible mechanism underlying the antidiabetic effect of C. volubile leaves in streptozotocin (STZ)‐induced diabetic rats using in vivo and in silico approach. Aqueous extract of C. volubile was prepared and its effect assessed on relevant enzymes associated with diabetes. Fifty Male Wistar rats (n=5) were randomly separated into ten groups. The induction of diabetes in rats was by a single intraperitoneal injection of STZ (65 mg/kg body weight) while C. volubile extract was administered orally to diabetic and non‐diabetic animals, at the doses of 50,100 and 200 mg/kg body weight respectively for 14 days. Also the interaction of compounds identified from C. volubile (HPLC‐DAD) on Takeda‐G‐protein‐receptor‐5 (TGR5), peroxisome proliferated activated receptor gamma (PPARγ) and dipeptidyl‐peptidase 4 (DPP‐4) was also investigated through molecular docking. Administration of C. volubile extract significantly reduced the elevated plasma glucose level and body weight, improved kidney functions, attenuated oxidative stress by decreasing malondialdehyde (MDA) levels, enhancing superoxide dismutase, catalase and glutathione peroxidase activities, reinstated the lipid profiles to nearly normal level and restored pancreatic histological integrity in diabetic rats. Rutin ranked highest among all the compounds identified in C. volubile with −8.3 kcal/mol binding energy with TGR5 with Glu343 and Glu291 −7.9 kcal/mol (PPARγ) and −9.5.kcal/mol (DPP‐4). Gln77, Arg125, Tyr240, Glu291, Glu343, Tyr 662 are among residues enhancing rutin binding to these proteins. The results revealed that C. volubile possess antidiabetic effects through the modulation of TGR5, PPARγ and DPP4. Rutin might be the lead compounds responsible for the antidiabetic effect of C. volubile justifying the use of this plant in traditional medicine
Increased Muscle Mass Restores a Healthy Vascular Endothelial Cell Phenotype in Obesity
Authors: Padgett Caleb A. , Butcher Joshua T. , Corley Zachary L. , Mintz James D. , Fulton David J. , Stepp David W.
Published: April 2020

Objective

Investigate the effects of hypermuscularity on expression of genes vital to healthy endothelial function in a model of obesity‐driven cardiovascular disease.

Methods

db/db mice, a well characterized model of human obesity, were crossed with mice lacking myostatin, a myokine that inhibits muscle growth, to generate lean, obese, and hypermuscular obese mice. Using a column separation technique, fresh endothelial cells were isolated from the aortic and mesenteric arteries and mRNA expression of genes vital to endothelial health were assessed by qPCR.

Results

The current study found that obesity significantly (p<0.05) increases expression of endothelial nitric oxide synthase (eNOS) and NADPH oxidase 1 (NOX1) by 15 to 25‐fold in both aortic and mesenteric endothelial cells in comparison to lean controls. Interestingly, expression of galectin‐3 (Gal‐3) in obesity increased significantly by 50‐fold in aortic endothelial cells, but 150‐fold in mesenteric endothelial cells. However, in endothelial cells from hypermuscular obese mice, overexpression of both NOX1 and Gal‐3 was ameliorated in both the aortic and mesenteric endothelium. These data indicate that hypermuscularity beneficially alters Gal‐3 overexpression, thereby decreasing injurious effects of NOX1 overexpression and restoring the endothelium to a favorable balance of eNOS and NOX1.

Conclusion

Hypermuscularity improves endothelial NOS/NOX balance by decreasing levels of galectin‐3, an upstream contributor of NOX1 expression. Inhibition of galectin‐3 may prove to be a viable therapeutic target to ameliorate obesity‐driven cardiovascular disease.
Effects of oral heat shock protein 60 on serum matrix metalloproteinase‐9 in atherosclerosis rats
Authors: Hao Chunyan , Duan Hubin , Zhang Huaping , Xi Ling , Zheng Xiaojun , Gong Yuhong
Published: April 2020

Objective

to study the effect of oral heat shock protein 60(HSP60) on serum matrix metalloproteinase‐9 (MMP‐9) in atherosclerosis (AS) rats.

Methods

40 healthy male SD rats were randomly divided into normal control group (group C), atherosclerosis intervention group (AS group), oral HSP60 group before building AS model (H1 group), oral HSP60 group after building AS model (H2 group), 10 rats in each group, weight 100 + 10 g. AS model was made by high fat feed. At 180 days of age, the rats were executed after obtaining the rats blood. MMP‐9 content in rats serum of each group were detected by enzyme‐linked immuno sorbent assay (ELISA).

Results

The MMP‐9 content in rats serum of group C, AS group, H1group and H2 group respectively are 0.43±0.15μg/mL,3.83±0.64μg/mL,0.91±0.20μg/mL,1.91±0.70μg/mL

Conclusion

The content of MMP‐9 in serum of atherosclerosis rats was higher than that of normal control group. Oral administration of HSP60 could reduce the content of MMP‐9 in serum, which had certain effect on maintaining the stability of fibrous plaque. The earlier oral administration of HSP60, the better the effect.

Support or Funding Information

This study was supported by the National Natural Science Foundation Youth Fund (30600637), China Postdoctral Foundation(2014M561207), the Shanxi Province Basic Research Program Youth Science and Technology Research Fund (2010021034‐4, 201601D011119), the Shanxi Scholarship Council of China (2011‐096 and Key Projects No. 4), Department of Human Resources and Social Security of Shanxi province, The science and technology research projects of health department of Shanxi Province(2016D011119), Science and technology development project of colleges of Shanxi Province, Innovation fund for college students in Shanxi Province, The Teaching Reform Program of Shanxi Higher Education, The Education Reform Project of Postgraduate Students in Shanxi Province. The Education Reform Project of Shanxi Medical University.
Transcriptional profiling of skeletal muscle during hypertrophy in the absence of satellite cell participation reveals muscle‐specific diversity and satellite cell dependent signaling networks
Authors: Englund Davis A. , Figueiredo Vandre , dungan cory , Murach Kevin , Peck Bailey , Dupont Alec , McCarthy John , Peterson Charlotte
Published: April 2020

The role of satellite cells (muscle stem cells) during hypertrophic growth remains to be fully elucidated. Previous findings are limited due to the mode of mechanical overload and a relatively narrow analysis of downstream effectors influenced by satellite cell depletion. The current study was designed to determine how the absence of satellite cells influences the transcriptome‐wide response and phenotypic adaptation to short‐ and long‐term periods of muscle growth in the oxidative soleus and the glycolytic/oxidative plantaris. We administered vehicle (SC+) or tamoxifen (SC−) to adult (6 months old) female Pax7‐DTA mice for 5 consecutive days to effectively deplete satellite cells. Following a 2‐week washout period, mice were subjected to progressive weighted wheel running (PoWeR) for 4 or 8 weeks or served as sedentary (locked running wheel) controls. After 4 and 8 weeks of PoWeR satellite cell and myonuclear density were significantly increased only in the muscles of SC+ mice. While muscle fiber size increased in both groups, growth was blunted at 4 and 8 weeks in the soleus and at 8 weeks in the plantaris of SC− mice. Further, measures of collagen demonstrate impaired extracellular matrix remodeling during muscle adaptation at both time points in the absence of satellite cells. RNA‐sequencing of the soleus and plantaris revealed muscle‐specific differences in the response to PoWeR as well as a dysregulated transcriptional profile during growth in the absence of satellite cells. These findings indicate satellite cells are required for optimal muscle growth and likely play a role in coordinating an efficacious transcriptional response for adaptations to exercise. We plan to further interrogate these findings at the myonuclear level via single‐nuclear sequencing, enabling a more targeted and fiber type‐specific analysis of signaling cascades dysregulated in the absence of satellite cell participation.

Support or Funding Information

Supported by AG060701 and AG049806 to CAP and JJM, AR071753 to KAM and TL1 TR001997 to DAE
3D‐printing of Stem Cells and Stromal Cells to Prime for Vascularization and Regeneration
Authors: Peirce-Cottler Shayn
Published: April 2020

Implanted engineered constructs intended for regenerating tissues face the immediate challenge of recruiting a microvasculature for the delivery of oxygen and nutrients, the trafficking of immune cells, and the regulation of interstitial fluid. The microcirculation is a hierarchical network of interconnected vessels that achieves this diverse range of functionality through its different components: arterioles, capillaries, and venules. The lumenized and branched structure of the microcirculation requires proper positioning of different cell types ‐‐ endothelial cells with an abluminal coating of pericytes and vascular smooth muscle cells ‐‐ and the establishment of a basement membrane between them. Spatially and temporally‐regulated molecular cues drive the cell‐to‐cell interactions that coordinate the assembly of these complex networks. Our lab combines computational modeling with 3D‐bioprinting to understand how microvessels assemble in vivo and to design and pattern them in vitro. We identified a sub‐population of cells in the stromal vascular fraction of adipose tissue that is capable of supporting capillaries and neo‐capillaries, much like native pericytes. We have developed techniques to exploit their use in murine models of diabetes, where angiogenesis is dysregulated and wound healing is delayed. Applications of our approach also include skeletal muscle regeneration and pancreatic islet re‐implantation.

Support or Funding Information

University of Virginia Center for Advanced Biomanufacturing University of Virginia School of Medicine Pinn Scholars
The Use of Surface Anatomy in Emergency Interventional Procedures: A Mixed Methods Analysis Comparing the Procedural Approaches of Clinicians
Authors: Fillmore Erin , Leech Caroline , Tunstall Richard
Published: April 2020

A good knowledge of surface anatomy forms an essential part of safe and effective clinical practice for many healthcare specialties. Understanding and using surface anatomy is key to interpreting normal anatomy on medical images and being able to describe the location, appearance and relationships of palpable anatomical structures. It is the definition of usable anatomy. However, evidence shows that even though clinicians rank surface anatomy as an essential aspect of anatomy needed to succeed in training, the way in which qualified clinicians use surface anatomical landmarks for common procedures varies greatly. This two‐phase sequential explanatory mixed methods study explored how practising emergency medicine and surgical clinicians, at various levels of qualification, use surface anatomy in order to perform a cricothyroidotomy, thoracostomy and/or thoracotomy. It examined what surface anatomy is used, how it is used, why it was used, and explored clinicians’ perceptions of the importance of surface anatomy in performing these procedures. Using this case study example, the findings illustrate that inconsistencies exist in the use and application of surface anatomy in practice. It highlights the need to more fully understand how surface anatomy is being used across specialities, across procedures and across levels of training. Finally, this study has shown there is a need for improved applied training in landmarking for core procedures that require a comprehensive knowledge of surface anatomy. Only in understanding the most common misconceptions and inconsistencies in surface anatomy’s use and application, can current guidelines help shape future teaching of the subject.

Support or Funding Information

None
Determining the effects of Wnt signaling in the alleviation of cholestasis via the promotion of hepatocyte transdifferentiation
Authors: Kosar Karis , Nejak-Bowen Kari , Li Qin
Published: April 2020

Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease characterized by bile duct inflammation and fibrosis, resulting in end‐stage liver disease and reduced life expectancy. Therefore, an effective treatment for PSC is needed. Hepatocytes exhibit remarkable plasticity and are known to be capable of transdifferentiating into cholangiocytes in models of biliary injury, which could create de novo ducts, repair damaged cholangiocytes, or contribute to bile detoxification. Previous studies utilizing in vitro organoid cultures and genetic mouse models found that β‐catenin and downstream targets are upregulated in hepatic organoid cultures, and mice expressing excess β‐catenin in the liver had an increased number of hepatocytes expressing cholangiocyte markers compared to wild type (WT) when subjected to cholestatic injury. These findings led to the hypothesis that Wnt/ß‐catenin signaling drives hepatocyte‐to‐cholangiocyte transdifferentiation during biliary injury. To test this hypothesis, we utilized lineage tracing in hepatic organoid cultures and TG mice expressing a mutated non‐degradable form of β‐catenin (S45D) in liver. We show that hepatocytes transdifferentiate to cholangiocytes in organoid cultures, and the cholangiocytes present are not from native contaminating cholangiocytes. We determined that TG mice fed DDC diet, which induces bile stasis, have: 1) improved serum ALP over time, indicating less biliary injury; 2) increased bile output compared to WT mice fed DDC diet; and 3) bile ducts populated with hepatocyte‐derived cholangiocytes. Through these studies we demonstrate that Wnt/ß‐catenin signaling catalyzes hepatocyte‐to‐cholangiocyte transdifferentiation, and activation of this pathway alleviates cholestasis in mouse models of PSC.

Support or Funding Information

NIH grant 1R01DK103775NIH training grant T32EB0010216NIH grant 1F31DK118802‐01
Brain 5‐HT deficiency prevents antidepressant‐like effects of high fat diet and blocks high fat diet‐induced GSK3β phosphorylation in the hippocampus
Authors: Sachs Benjamin , Karth Michelle , Baugher Brittany , Daly Nicole , Karth Melinda , Gironda Stephen
Published: April 2020

Obesity is associated with an increased risk of depression and anxiety disorders, but the nature of the relationship(s) between obesity and mental illness remain highly controversial. Some argue that depression and/or anxiety lead to increased consumption of ‘comfort foods’ to reduce negative affect and that chronic consumption of these foods promotes obesity. Alternatively, it has been suggested that chronic excessive consumption of highly palatable foods, such as those high in fats, could induce negative affective states in susceptible individuals. However, the genetic factors that influence food consumption and behavioral responses to high fat diets (HFDs) remain largely unknown. The brain serotonin (5‐HT) system has long been implicated in both the development and treatment of mental illness. Preclinical studies have shown that low brain 5‐HT exacerbates depression‐ and anxiety‐like behavior induced by stress and blocks reductions in depression‐like behavior induced by antidepressants, but the effects of brain 5‐HT deficiency on responses to HFD have not been explored. The current work used genetically modified mice to evaluate the effects of low brain 5‐HT on behavioral and molecular alterations induced by chronic exposure to HFD. Real‐time PCR was used to measure mRNA expression, and Western blotting was used to study protein phosphorylation. Our results reveal that HFD decreases depression‐like behavior and increases some anxiety‐like behaviors in wild‐type mice. However, genetic brain 5‐HT deficiency blocks HFD‐induced reductions in forced swim immobility and prevents HFD‐induced increases in hippocampal GSK3β phosphorylation. These effects occur despite the fact that low 5‐HT does not influence HFD‐induced changes in body weight or anxiety‐like behavior in the novel open field test or the elevated plus maze. Together, our results suggest that although brain 5‐HT deficiency does not alter HFD intake, low brain 5‐HT prevents therapeutic‐like responses to HFD and blocks the inhibition of GSK3 by HFD. Although GSK3 inhibition has been shown to lead to antidepressant‐like effects, whether GSK3 inhibition is required for the antidepressant‐like effects of HFD has not been established. Nonetheless, our results indicate that brain 5‐HT plays a major role in mediating some of the effects of HFD, which could help explain the complex relationships between obesity and mental illness.
Activation of Nogo‐B receptor expression ameliorates type 2 diabetes in mice by improving insulin sensitivity
Authors: Chen Yi , Li Qi , Duan Yajun , Yang Xiaoxiao , Chen Yuanli , Han Jihong
Published: April 2020

Reduction of insulin resistance/improvement of insulin sensitivity is the most effective treatment for type 2 diabetes (T2D). We previously reported Nogo‐B receptor (NGBR) is a specific negative regulator for liver X receptor alpha (LXRα)‐dependent hepatic lipogenesis, indicating NGBR may play an important role in hepatic lipid metabolism. However, it remains unknown if NGBR is involved in glucose metabolism and insulin sensitivity. Herein, we report the role of NGBR expression in insulin resistance and T2D development.

In vitro, the role of NGBR in insulin sensitivity was analyzed by NGBR knockdown/overexpression in hepatic cell line. The pathophysiological role of NGBR in insulin sensitivity was analyzed in high‐fat diet (HFD)/streptozotocin (STZ)‐induced diabetic mice infected with recombinant adenovirus expressing NGBR by tail vein injection. We found inhibition of NGBR expression by siRNA decreased insulin sensitivity, and attenuated adiponectin‐activated AMPKa phosphorylation in hepatocytes. Reciprocally, NGBR overexpression enhanced insulin response. In vivo, NGBR overexpression was observed in mouse liver after infection of recombinant adenovirus expressing NGBR. Associated with NGBR overexpression, blood glucose was reduced while insulin sensitivity/glucose homeostasis was enhanced. NGBR overexpression also decreased triglyceride and NEFA levels in both liver and serum, and attenuated the injury in pancreatic islets. Furthermore, genes related to ER stress and mitochondrial functions in skeletal muscles and inflammation in adipose tissues were improved by hepatic NGBR overexpression. In conclusion, our study implicates the importance of understanding the role of hepatic NGBR in insulin sensitivity and treatment of T2D.
Renal sympathetic denervation attenuates congestive heart failure in angiotensin II‐dependent hypertension: studies with Ren‐2 transgenic hypertensive rats with aorto‐caval fistula
Authors: Honetschlagerova Zuzana , Melenovsky Vojtech
Published: April 2020

Objective

We hypothesized that renal denervation (RDN) attenuates the progression of aorto‐caval fistula (ACF)‐induced heart failure (HF) and the development of renal dysfunction in Ren‐2 transgenic rats (TGR), a model of ANG II‐dependent hypertension.

Methods

RDN (severing renal nerve fibers, followed by phenol application) was done one week after creation of ACF; the follow‐up period was 70 days. The animals studied were: 1) Sham‐operated TGR (initial n = 8); 2) Sham‐operated TGR + RDN (n = 9); 3) ACF TGR (n = 31); 4) ACF TGR + RDN (n = 34). In separate groups (n = 8 in each), three weeks after induction of ACF, renal artery blood flow (RBF, Transonic probe) responses were determined to intrarenal ANG II (2 and 8 ng), norepinephrine (NE) (20 and 40 ng) and acetylcholine (Ach) (10 and 40 ng).

Results

Untreated ACF TGR began to die 3 weeks after induction of ACF and the final survival rate was 10% (3 from 31). RDN substantially improved the final survival rate to 50% (17 from 34). Basal RBF was significantly lower in ACF TGR than in sham‐operated TGR (6.9 ± 0.4 vs. 10.1 ± 0.5 ml.min−1.g−1, p<0.05) and RDN did not alter it in any group. Both doses of ANG II decreased RBF more in ACF TGR than in sham‐operated TGR (−17 ± 2% vs. −9 ± 2% and −42 ± 3% vs. −25 ± 2%, p<0.05 in both cases) and RDN increased RBF responsiveness to ANG II in ACF TGR (to −29 ± 3% and to −74 ± 3%, p<0.05 in both cases) as well as in sham‐operated TGR (to −21 ± 3% and −42 ± 3%, p<0.05). Intrarenal NE comparably decreased RBF in ACF TGR and sham‐operated TGR, and RDN increased RBF responsiveness in both groups. Intrarenal Ach increased RBF significantly more in ACF TGR than in sham‐operated TGR (+24 ± 2% vs. +11 ± 2% and +26 ± 2% vs. +13 ± 2%, p<0.05 in both cases) and RDN did not alter it in any group.

Conclusion

The results show that RDN significantly improved survival rate in ACF TGR, however this beneficial effect was not associated with improvement of reduced RBF or with attenuation of exaggerated renal vascular responsiveness to ANG II.

Support or Funding Information

Supported by the Ministry of Health of the Czech Republic grant No. NV‐18‐02‐00053 awarded to L.Č. All rights reserved. Supported by MH CZ ‐ DRO („Institute for Clinical and Experimental Medicine – IKEM, IN 00023001“).