bluuebunny/crossref_metadata_2025 huggingface dataset:
Fractional Hedonic Games
Authors: Aziz Haris , Brandl Florian , Brandt Felix , Harrenstein Paul , Olsen Martin , Peters Dominik
Published: June 2019

The work we present in this article initiated the formal study of
fractional hedonic games
(FHGs), coalition formation games in which the utility of a player is the average value he ascribes to the members of his coalition. Among other settings, this covers situations in which players only distinguish between friends and non-friends and desire to be in a coalition in which the fraction of friends is maximal. FHGs thus not only constitute a natural class of succinctly representable coalition formation games but also provide an interesting framework for network clustering. We propose a number of conditions under which the core of FHGs is non-empty and provide algorithms for computing a core stable outcome. By contrast, we show that the core may be empty in other cases, and that it is computationally hard in general to decide non-emptiness of the core.
Land-Management Options for Greenhouse Gas Removal and Their Impacts on Ecosystem Services and the Sustainable Development Goals
Authors: Smith Pete , Adams Justin , Beerling David J. , Beringer Tim , Calvin Katherine V. , Fuss Sabine , Griscom Bronson , Hagemann Nikolas , Kammann Claudia , Kraxner Florian , Minx Jan C. , Popp Alexander , Renforth Phil , Vicente Vicente Jose Luis , Keesstra Saskia
Published: June 2019

Land-management options for greenhouse gas removal (GGR) include afforestation or reforestation (AR), wetland restoration, soil carbon sequestration (SCS), biochar, terrestrial enhanced weathering (TEW), and bioenergy with carbon capture and storage (BECCS). We assess the opportunities and risks associated with these options through the lens of their potential impacts on ecosystem services (Nature's Contributions to People; NCPs) and the United Nations Sustainable Development Goals (SDGs). We find that all land-based GGR options contribute positively to at least some NCPs and SDGs. Wetland restoration and SCS almost exclusively deliver positive impacts. A few GGR options, such as afforestation, BECCS, and biochar potentially impact negatively some NCPs and SDGs, particularly when implemented at scale, largely through competition for land. For those that present risks or are least understood, more research is required, and demonstration projects need to proceed with caution. For options that present low risks and provide cobenefits, implementation can proceed more rapidly following no-regrets principles.
The Effects of Folic Acid Administration on Cardiac Oxidative Stress and Cardiovascular Biomarkers in Diabetic Rats
Authors: Mutavdzin Slavica , Gopcevic Kristina , Stankovic Sanja , Jakovljevic Uzelac Jovana , Labudovic Borovic Milica , Djuric Dragan
Published: June 2019

The aim of this study was to examine the effects of folic acid administration on the antioxidant enzyme (superoxide dismutase (SOD) and catalase (CAT)) activities, lactate and malate dehydrogenase (LDH and MDH) activities, and certain LDH and MDH isoform distribution in the cardiac tissue of diabetic Wistar male rats. Diabetes mellitus (DM) was induced by streptozotocin (STZ). There were five groups: C1—control (physiological saline 1 ml/kg, i.p. one day), C2—control with daily physiological saline treatment (1 ml/kg, i.p. 28 days), DM—diabetes mellitus (STZ 100 mg/kg in physiological saline, i.p. one day), FA—folic acid (5 mg/kg in physiological saline, i.p. 28 days), and DM+FA—diabetes mellitus and folic acid group (STZ 100 mg/kg in physiological saline, i.p. one day, and folic acid 5 mg/kg in physiological saline, i.p. 28 days). After four weeks, animal hearts were isolated for measurement of enzyme activities, as well as for histomorphometry analyses. An elevated glucose level and a decreased insulin level were obtained in the DM group. SOD, CAT, and MDH activities were elevated in the DM group, while there was no difference in LDH activity among the groups. In all tested groups, four LDH and three MDH isoforms were detected in the heart tissue, but with differences in their relative activities among the groups. Left ventricular cardiomyocyte transversal diameters were significantly smaller in both diabetic groups. Folic acid treatment of diabetic rats induced a reduced glucose level and reduced CAT, SOD, and MDH activities and alleviated the decrease in cardiomyocyte diameters. In conclusion, increased activities of antioxidant enzymes and MDH may be the consequence of oxidative stress caused by DM. Administration of the folic acid has a protective effect since it leads to reduction in glycemia and activities of the certain examined enzymes in the rats with experimentally induced DM.
Study on Cleaning Effect of Different Water Flows on the Pulsed Cavitating Jet Nozzle
Authors: Liu Chengting , Liu Gang , Yan Zuoxiu
Published: June 2019

The method of cleaning by self‐excited pulsed cavitating jet was proposed according to cleaning characteristics and requirements of large storage equipment. This method has many advantages compared with other cleaning methods. In order to achieve the optimum cleaning effects, experimental research on working status of the nozzle at different flow rates was conducted and analysis was carried out from the following four aspects: cavitation morphology, pressure pulse frequency, velocity fluctuation amplitude, and erosion effect. The research results showed that flushing effects in the nozzle without cavitation were far below those with cavitation; when the flow rate increased to over 2.7 m3/h, cavitation began to appear in the chamber. When Q = 7.2 m3/h, the velocity fluctuation amplitude was about 17.25 m and pressure fluctuation occurred for 86 times (maximum) within 1 s. During the experiment on erosion effects, the flow rate had little influence on outside diameter of the erosion circle. The erosion rate increased with the increase of the flow rate, reached the peak value at Q = 7.2 m3/h, but slightly decreased subsequently.
Predictors of Hypertension among Adult Female Population in Kpone-Katamanso District, Ghana
Authors: Acheampong Kwabena , Nyamari Jackim M. , Ganu Daniel , Appiah Stella , Pan Xiongfeng , Kaminga Atipatsa , Liu Aizhong
Published: June 2019

Background. Hypertension is an independent risk factor of cardiovascular disease, which is one of the biggest health challenges today. The objective of this study was to estimate the prevalence of the problem and other factors related to hypertension among women who are 25 years and above. Methods. A community-based cross-sectional study was conducted from September and November 2017. A multistage cluster sampling technique was used to select the study participants. The data was collected using a structured questionnaire and physical measurements adapted from “WHO STEPwise approach to chronic disease risk factor surveillance (STEPS).” Data were examined using the SPSS program IBM version 20. Descriptive statistics, including proportions, frequencies, and cross-tabulations, were used to summarize the study variables. A binary logistic regression was fitted variable with a p value of < 0.7. The bivariable analyses were entered in the multivariable analysis to control the possible effect of confounders. Multivariable logistic regression analysis was used to identify factors associated with hypertension. The Adjusted Odds Ratio (AOR) with a 95 % Confidence Interval (CI) was computed to show the level of certainty. A p value of <0.05 was considered statistically significant. Results. The study indicated that the prevalence of hypertension (BP ≥ 140/90 mmHg) was 33.8% (95% CI 27.4-40.2) which increased with age. At the time of the study, women aged 45-64 years [AOR =2.19, (95% CI: 1.11-4.34, p<0.02)] and 65+ years [AOR =5.13, (95% CI: 2.20-11.99), p<0.001] were two to five times as likely as those with age of 25-44 years to be hypertensive. Women who had a higher body mass index (BMI) ≥30 kg/m2 were two times as likely as those with normal weight to be hypertensive [AOR 2.38, (95% CI; 1.14-4.95, p<0.02)]. Women who did not consume fresh fruit daily were three times as likely as those women who consume fresh fruit daily to be hypertensive [AOR 3.17 (95% CI; 1.05-9.55, p<0.04)]. Conclusion. Increasing age, obesity, and women who did not consume fresh fruits daily were associated with hypertension, indicating opportunities for health education and other prevention measures.
Novel Method of Remotely Monitoring the Face-Device Distance and Face Illuminance Using Mobile Devices: A Pilot Study
Authors: Salmerón-Campillo Rosa María , Jaskulski Mateusz , Lara-Cánovas Sergio , González-Méijome José Manuel , López-Gil Norberto
Published: June 2019

Specially developed software (app) was written for handheld electronic devices that uses the device camera and light detector for real-time monitoring of near-work distance and environmental lighting. A pilot study of this novel app employed children using tablet computers in a classroom. Measurements of face-device distance and face illuminance were obtained from two schools where tablets were used regularly. Children were divided randomly into a control group (CG) and intervention group (IG). The app was calibrated in a lab and configured to store average values every 20 seconds in a remote database. In both groups, the app recorded data only when a child’s face was present in the camera image. The app darkened the screen for the IG when the face-device distance was shorter than 40 cm. The total mean face-device distance was 36.8 ± 5.7 cm in CG and 47.2 ± 6.5 cm in IG. Children in IG had to accommodate approximately 0.6 D less when using their devices. The mean classroom face illuminance was 980 ± 350 lux in School #1 and 750 ± 400 lux in School #2. The novel method of remotely monitoring and controlling the face-device distance and illuminance can potentially open new paths for myopia prevention and myopia control.
Diagnostic Radiation Exposure in Patients with Inflammatory Bowel Disease
Authors: Langevin Catherine , Normandeau Lysanne , Bouin Mickael
Published: June 2019

Background. Because of the chronic and relapsing nature of inflammatory bowel disease (IBD), which often requires characterization with CT scan, IBD patients might be exposed to a large amount of radiation. As a cumulative effective dose (CED) ≥ 100 mSv is considered significant for stochastic risks of cancer, it is important to monitor and control the radiation exposure of the IBD patients. In the present work, we aimed to quantify the mean CED in IBD patients to assess any harmful effects of radiation. Methods. This study includes 200 IBD patients, identified retrospectively, from the outpatient clinics of the Centre Hospitalier de l’Université de Montréal between January 1, 2010, and February 15, 2017, from the gastroenterologists’ patients lists. The number and type of each radiology test performed were listed for each patient during the study period and the CED was calculated using our institution’s dose index when available and standardized tables. Results. Among the 200 IBD patients, 157 patients had Crohn’s disease (CD), 41 had ulcerative colitis (UC), and 2 had indeterminate colitis. The mean CED for IBD patients was 23.1 ± 45.2 mSv during a mean follow-up duration of 4.3 years. CED was higher among patients with CD than with UC (27.5 ± 49.5 versus 6.8 ± 14.8 mSv; p<0.01). Six patients were exposed to a high CED (>100 mSv) and all had CD. Conclusion. While potentially harmful levels of radiation exposure are of concern in only a small number of patients, strategies to limit such exposure are encouraged when clinically appropriate.
Vibration in a Multistage Centrifugal Pump under Varied Conditions
Authors: Bai Ling , Zhou Ling , Jiang Xiaoping , Pang Qinglong , Ye Daoxing
Published: June 2019

Multistage pumps are intended to improve designs with low‐vibration and ‐noise features as the industry applications increase the technical requirements. In this frame, it becomes really important to fully understand the vibration patterns of these kinds of complex machines. In this study, a vibration test bench was established to examine the vibration and stability of a cantilever multistage centrifugal pump under different flow rates. The vibration spectrum diagrams for the inlet and outlet sections and the pump body were evaluated under varied flow conditions. Results showed the effects of operational conditions on the vibration of the cantilever multistage centrifugal pump. Vibration velocity was primarily caused by mass unbalance at the shut‐off flow rate point. Under different flow conditions, the blade passing frequency (BPF) and two times the blade passing frequency (2BPF) were the main excitation frequencies. The vibration frequency of the final pump body remained at the BPF under different flow conditions due to the contact with the outlet section. The major type of vibration frequency for the inlet and outlet was high frequency.
An Approximation of Minimum Initial Capital of Investment Discrete Time Surplus Process with Weibull Distribution in a Reinsurance Company
Authors: Boonta Soontorn , Boonthiem Somchit
Published: June 2019

Catastrophe is a loss that has a low probability of occurring but can lead to high-cost claims. This paper uses the data of fire accidents from a reinsurance company in Thailand for an experiment. Our study is in two parts. First, we approximate the parameters of a Weibull distribution. We compare the parameter estimation using a direct search method with other frequently used methods, such as the least squares method, the maximum likelihood estimation, and the method of moments. The results show that the direct search method approximates the parameters more precisely than other frequently used methods (to four-digit accuracy). Second, we approximate the minimum initial capital (MIC) a reinsurance company has to hold under a given ruin probability (insolvency probability) by using parameters from the first part. Finally, we show MIC with varying the premium rate.
An Approach to Computing Multipoint Inversion and Multiray Surface Intersection on Parametric Surface
Authors: Jingyu Pei , Xiaoping Wang , Leen Zhang
Published: June 2019

This article presents a method for multipoint inversion and multiray surface intersection problem on the parametric surface. By combining tracing along the surface and classical Newton iteration, it can solve point inversion and ray‐surface intersection issues concerning a large number of points or rays in a stable and high‐speed way. What is more, the computation result can approximate to exact solutions with arbitrary precision because of the self‐correction of Newton‐Raphson iteration. The main ideas are adopting a scheme tracing along the surface to obtain a good initial point, which is close to the desired point with any prescribed precision, and conducting Newton iteration process with the point as a start point to compute desired parameters. The new method enhances greatly iterative convergence rate compared with traditional Newton’s iteration related methods. In addition, it has a better performance than traditional methods, especially in dealing with multipoint inversion and multiray surface intersection problems. The result shows that the new method is superior to them in both speed and stability and can be widely applied to industrial and research field related to CAD and CG.
Biological versus Clinical Risk Factors in Acute Myeloid Leukemia: Is There a Winner?
Authors: Malagola M. , Polverelli N. , Cancelli V. , Morello E. , Turra A. , Borlenghi E. , Cattina F. , Rambaldi B. , Bernardi S. , Zanaglio C. , Dereli Eke Elif , Gandolfi L. , Farina M. , Russo D.
Published: June 2019

We present a case of a patient with a three-month history of peripheral blood cytopenia without a confirmed diagnosis of myelodysplastic syndrome, who developed a favourable-risk acute myeloid leukemia (AML), according to the European Leukemia Net (ELN) criteria. The patient achieved a complete remission with incomplete platelet recovery (CRi) after induction. The patient achieved the morphological CR after the first consolidation and completed the first-line treatment with a syngeneic stem cell transplantation (SCT). A disease relapse occurred after one year of CR (blast cell count in the bone marrow 15%), and the patient was offered a haplo-SCT, which he refused due to personal reasons. In this paper, we discuss the interplay between clinical and biological risk factors in non-high-risk AML patients and speculate that some old clinical risk factors (e.g., age of the patient, achievement of CR after induction, and previous history of myelodysplastic syndrome) may still impact on the treatment decision algorithm of some of these patients.
Analysis of Nonlinear Coupled Systems of Impulsive Fractional Differential Equations with Hadamard Derivatives
Authors: Riaz Usman , Zada Akbar , Ali Zeeshan , Ahmad Manzoor , Xu Jiafa , Fu Zhengqing
Published: June 2019

This work is committed to establishing the assumptions essential for at least one and unique solution of a switched coupled system of impulsive fractional differential equations having derivative of Hadamard type. Using Krasnoselskii’s fixed point theorem, the existence, as well as uniqueness results, is obtained. Along with this, different kinds of Hyers–Ulam stability are discussed. For supporting the theory, example is provided.
Recombinant α-Klotho Protein Alleviated Acute Cardiorenal Injury in a Mouse Model of Lipopolysaccharide-Induced Septic Cardiorenal Syndrome Type 5
Authors: Liu Xi , Niu Yangyang , Zhang Xiaoqin , Zhang Yingying , Yu Ying , Huang Jieli , Li Jiangtao , Yu Chen
Published: June 2019

Background and Aims. Klotho is an aging-suppressor gene mainly expressed in the renal tubules. The klotho gene encodes the α-klotho protein, which has many functions. Previous studies have found that α-klotho protein has a cardiorenal protective function. α-Klotho deficiency renders the kidney more susceptible to injury and results in cardiovascular calcification and left ventricular hypertrophy in chronic kidney disease. However, the role of α-klotho in acute heart injury and acute kidney injury with sepsis remains unknown. This study aimed to investigate the effects and mechanisms of α-klotho in septic cardiorenal injury. Methods. Male 8-week-old C57BL/6 mice were randomly assigned to the control group, lipopolysaccharide (LPS; 10 mg/kg) group, LPS (10 mg/kg)+α-klotho (0.01 mg/kg) group, and LPS (10 mg/kg)+α-klotho (0.02 mg/kg) group. Recombinant α-klotho was intraperitoneally injected an hour before LPS injection. Mice were euthanized at 24 h after LPS injection. The serum troponin, brain natriuretic peptide (BNP), neutrophil gelatinase-associated lipocalin (NGAL), and creatinine levels were measured in all groups at 24 h. Biomarkers of mice heart apoptosis, inflammation, oxidative stress, and endoplasmic reticulum stress, such as caspase-3, interleukin 1 (IL-1), reactive oxygen species (ROS), and glucose-regulated protein 78 (GRP78), were also measured. Results. α-Klotho was mainly expressed in mice kidneys and was undetectable in the control mice hearts. α-Klotho substantially decreased after LPS injection. In the LPS group, the serum troponin levels significantly increased as early as 6 h (p<0.05) after LPS injection, while the BNP, NGAL, and creatinine levels significantly increased at 24 h (p<0.05). Pretreatment with α-klotho significantly ameliorated acute cardiorenal injury. In the LPS+α-klotho (0.01 mg/kg) group, the levels of apoptosis, inflammation, and oxidative stress were decreased, while the level of endoplasmic reticulum stress was elevated. Conclusions. α-Klotho significantly alleviates acute cardiorenal injury in LPS-induced septic cardiorenal injury due to the inhibition of apoptosis, inflammation, and oxidation, as well as the regulation of endoplasmic reticulum stress levels.
Space Regaining Made Easy: The Case of a Severely Infraoccluded Primary Molar
Authors: Garcovich Daniele , Aiuto Riccardo , Martin Milagros Adobes
Published: June 2019

Infraocclusion of deciduous molars is a quite common but challenging clinical situation that a paediatric dentist has to face in his everyday practice. This anomaly can lead to space loss, eruption disturbances of the permanent successor, and deformation of the occlusal plane. A case of a severely infraoccluded primary molar is presented. The treatment was carried out using a compressed NiTi wire applied only to the adjacent teeth. In three months, the space was recovered, and the infraoccluded temporary molar was extracted. After one year, the permanent successor erupted without any complication. The technique presented can be considered minimally invasive, and it involves cost- and time-efficient mechanics.
Spatial and Temporal Characteristics of Cirrus Clouds over the Tibetan Plateau Based on CALIPSO and AIRS Observations
Authors: Liu Hailei , Chen Yuan , Zhang Shenglan , Ding Jilie , Deng Xiaobo , Liu Xingzhong
Published: June 2019

The spatial and temporal distribution characteristics of high clouds over the Tibetan Plateau (TP) were studied using the Atmospheric Infrared Sounder (AIRS) and the GCM-Oriented CALIPSO Cloud Product (CALIPSO-GOCCP) monthly mean cloud products from 2007 to 2017. The high clouds over the TP are dominated by cirrus and show seasonal variation characteristics. There were two distinct areas with the high occurrence of cirrus clouds in the area (0°–60°N, 75°–103°E). One was located in the regions from the equator to 25°N, and the other was within the latitude belt from 30° to 40°N. From January to May, cirrus clouds mainly occurred in the central and northern parts of the TP (30° to 40°N), and the cirrus cloud fraction increased from January and reached its maximum (∼0.51) in April. From June to August, cirrus clouds mainly occurred in the southern part of the TP during summer. The cirrus clouds over the southern TP were relatively high (located in 10–17 km) and manifested northward and southward movements. The ice clouds in the southern TP are associated with plateau deep convection activities and abundant vapor transmitted by the Asian monsoon. Cirrus clouds over the northern and central TP may be relevant to the atmospheric lift by an approaching cold front and topographic lifting. Moreover, the high clouds below 11 km are dominated by opaque clouds, while the nonopaque (or thin) and opaque (or thick) clouds above 11 km are comparable.
Effect of Ligustrazine on Endometrium Injury of Thin Endometrium Rats
Authors: Ye Qing , Zhang Yu , Fu Jiulu , Zou Yi , Zhao Wei , Chen Chen , Liu Kun
Published: June 2019

The purpose of this experiment is to establish a rat model of thin endometrium and to explore the effect of ligustrazine on the thin endometrium of rats. The thin endometrium model was made by using infusing absolute ethyl alcohol into the uterine cavity. The thickness of endometrium was measured. Hematoxylin-Eosin (HE) staining was used to observe the histopathological changes of endometrium. The mRNA levels of VEGF, VEGFR-2, PI3K, and AKT were detected by RT-PCR. Western blotting was used to detect the levels of VEGF, VEGFR-2, PI3K, and AKT in endometrial tissue. The thickness of endometrium in the model group was significantly thinner than that in the control group. Compared with the model group, the thickness of endometrium in ligustrazine group was increased. HE staining shown that ligustrazine restored the histopathological changes of endometrium. RT-PCR and Western Blotting results showed that the mRNA and protein levels of VEGF, VEGFR-2, PI3K, and AKT in the model group were significantly decreased compared with the control group, while ligustrazine restored the changes. Ligustrazine can improve the morphology of endometrium, can promote the growth of endometrium, and has obvious therapeutic effect. Its mechanism is related to the activation of PI3K/Akt signaling pathway through upregulation of VEGF and VEGFR-2 expression to induce the repair of thin endometrium in rats.
Optimization of the Mixture Design of Low‐CO2 High‐Strength Concrete Containing Silica Fume
Authors: Kwon Seung-Jun , Wang Xiao-Yong
Published: June 2019

As abundant CO2 is released by high‐strength concrete due to its high binder content, the reduction of CO2 emissions has become increasingly important. This study proposed a general procedure to optimize the mixture design of low‐CO2 high‐strength concrete containing silica fume. First, the equations for evaluating strength and slump were regressed based on available experimental results. CO2 emissions were calculated based on the concrete mixtures and the unit CO2 emissions of the concrete components. By using the genetic algorithm, the concrete mixtures with the lowest CO2 emissions were determined by considering various constraints. Second, the cost of concrete was calculated based on the concrete mixtures and the unit cost of the concrete components. Similarly, the concrete mixtures with the lowest cost were determined based on the genetic algorithm. We found that, in some cases, the mixtures with the lowest CO2 emissions were different from those with the lowest cost. Third, through adding the constraint equation of cost, Pareto optimal mixtures with relatively lower CO2 emissions and lower cost were determined. In summary, the proposed technique is valuable for designing high‐strength concrete considering both CO2 emissions and cost.
Alterations in Organismal Physiology, Impaired Stress Resistance, and Accelerated Aging inDrosophilaFlies Adapted to Multigenerational Proteome Instability
Authors: Manola Maria S. , Tsakiri Eleni N. , Trougakos Ioannis P.
Published: June 2019

Being an assembly of highly sophisticated protein machines, cells depend heavily on proteostatic modules functionality and on adequate supply of energetic molecules for maintaining proteome stability. Yet, our understanding of the adaptations induced by multigenerational proteotoxic stress is limited. We report here that multigenerational (>80 generations) proteotoxic stress in OregonRflies induced by constant exposure to developmentally nonlethal doses of the proteasome inhibitor bortezomib (BTZ) (G80-BTZflies) increased proteome instability and redox imbalance, reduced fecundity and body size, and caused neuromuscular defects; it also accelerated aging.G80-BTZflies were mildly resistant to increased doses of BTZ and showed no age-related loss of proteasome activity; these adaptations correlated with sustained upregulation of proteostatic modules, which however occurred at the cost of minimal responses to increased BTZ doses and increased susceptibility to various types of additional proteotoxic stress, namely, autophagy inhibition or thermal stress. Multigenerational proteome instability and redox imbalance also caused metabolic reprogramming being evidenced by altered mitochondrial biogenesis and suppressed insulin/IGF-like signaling (IIS) inG80-BTZflies. The toxic effects of multigenerational proteome instability could be partially mitigated by a low-protein diet that extendedG80-BTZflies’ longevity. Overall, persistent proteotoxic stress triggers a highly conserved adaptive metabolic response mediated by the IIS pathway, which reallocates resources from growth and longevity to somatic preservation and stress tolerance. Yet, these trade-off adaptations occur at the cost of accelerated aging and/or reduced tolerance to additional stress, illustrating the limited buffering capacity of survival pathways.
Transmission of Normal P‐Waves across a Single Joint Based on g‐λ Model
Authors: Fan Zhanfeng , Zhang Jichun , Xu Hua , Cai Jianhua
Published: June 2019

This paper investigates the wave transmission and reflection of an elastic P‐wave at a single joint for normal incidence. First, considering a coupled joint (correction parameter λ, 0 < λ < 1), a normal deformation constitutive model of the joint (g‐λ model) under static or quasi‐static loading is introduced and then extended to dynamic loading. The nonlinearity of the joint stress‐deformation curve increases with increasing λ. Second, the interaction between the P‐wave and the joint is investigated by using the method of characteristics and the displacement discontinuity method to deduce the differential expression of the transmitted wave’s particle velocity. The approximate analytical expressions of the transmission and reflection coefficients are obtained according to the Lemaitre equivalent strain assumption. Third, parametric studies are conducted to evaluate the effects of λ on transmission characteristics for a normally incident P‐wave at a single joint. The results show that the particle velocity of the transmitted wave depends on λ. When λ takes the limit values 0 and 1, the transmitted wave’s particle velocities are then consistent with the conclusions of the classical exponential model and the Barton–Bandis model. In addition, the transmission and reflection coefficients are discussed with respect to λ and also to the ratio of the joint closure to the maximum allowable joint closure.
High Thymic Output of Effector CD4+ Cells May Lead to a Treg : T Effector Imbalance in the Periphery in NOD Mice
Authors: Zhao Yuan , Alard Pascale , Kosiewicz Michele M.
Published: June 2019

Regulatory T cells (Tregs) play a critical role in controlling autoreactive T cells, and quantitative and/or qualitative deficiencies in Tregs are associated with autoimmune diseases, including type 1 diabetes (T1D), in both humans and mice. Both the incidence of T1D and percentages of peripheral Tregs in NOD mice vary considerably between animal facilities. In our animal facility, the incidence of T1D in NOD mice is high at 90-100% and the percentages of peripheral CD4+Foxp3+ cells in ~9-10-week-old female NOD mice are decreased compared to control (B6) mice shortly before high glucose is first detected (~12 weeks). These data suggest that there is an imbalance between Tregs and potentially pathogenic effector T cells at this age that could have significant impact on disease progression to overt diabetes. The goal of the current study was to investigate mechanisms that play a role in peripheral Treg : T effector cell balance in NOD mice, including differences in persistence/survival, peripheral homeostatic proliferation, and thymic production and output of CD4+ T cells. We found no differences in persistence/survival or homeostatic proliferation of either Tregs or effector T cells between NOD and B6 mice. Furthermore, although the percentages and absolute numbers of CD4+Foxp3+ cells in thymus were not decreased in NOD compared to B6 mice, the percentage of CD4+ recent thymic emigrants (RTE) that were Foxp3+ was significantly lower in 9-week-old NOD mice. Interestingly, the thymic output of CD4+Foxp3+ cells was not lower in NOD mice, whereas the thymic output of CD4+Foxp3- cells was significantly higher in NOD mice at that age compared to B6 mice. These data suggest that the higher thymic output of CD4+Foxp3- T cells contributes, at least in part, to the lower percentages of peripheral CD4+Foxp3+ Tregs in NOD mice and an imbalance between Tregs and T effector cells that may contribute to the development of full-blown diabetes.
Multiparametric MRI and Coregistered Histology Identify Tumor Habitats in Breast Cancer Mouse Models
Authors: Jardim-Perassi Bruna V. , Huang Suning , Dominguez-Viqueira William , Poleszczuk Jan , Budzevich Mikalai M. , Abdalah Mahmoud A. , Pillai Smitha R. , Ruiz Epifanio , Bui Marilyn M. , Zuccari Debora A.P.C. , Gillies Robert J. , Martinez Gary V.
Published: June 2019

It is well-recognized that solid tumors are genomically, anatomically, and physiologically heterogeneous. In general, more heterogeneous tumors have poorer outcomes, likely due to the increased probability of harboring therapy-resistant cells and regions. It is hypothesized that the genomic and physiologic heterogeneity are related, because physiologically distinct regions will exert variable selection pressures leading to the outgrowth of clones with variable genomic/proteomic profiles. To investigate this, methods must be in place to interrogate and define, at the microscopic scale, the cytotypes that exist within physiologically distinct subregions (“habitats”) that are present at mesoscopic scales. MRI provides a noninvasive approach to interrogate physiologically distinct local environments, due to the biophysical principles that govern MRI signal generation. Here, we interrogate different physiologic parameters, such as perfusion, cell density, and edema, using multiparametric MRI (mpMRI). Signals from six different acquisition schema were combined voxel-by-voxel into four clusters identified using a Gaussian mixture model. These were compared with histologic and IHC characterizations of sections that were coregistered using MRI-guided 3D printed tumor molds. Specifically, we identified a specific set of MRI parameters to classify viable-normoxic, viable-hypoxic, nonviable-hypoxic, and nonviable-normoxic tissue types within orthotopic 4T1 and MDA-MB-231 breast tumors. This is the first coregistered study to show that mpMRI can be used to define physiologically distinct tumor habitats within breast tumor models.

Significance:

This study demonstrates that noninvasive imaging metrics can be used to distinguish subregions within heterogeneous tumors with histopathologic correlation.
miRNAs and Long-term Breast Cancer Survival: Evidence from the WHEL Study
Authors: Natarajan Loki , Pu Minya , Davies Sherri R. , Vickery Tammi L. , Nelson Sandahl H. , Pittman Emily , Parker Barbara A. , Ellis Matthew J. , Flatt Shirley W. , Mardis Elaine R. , Marinac Catherine R. , Pierce John P. , Messer Karen
Published: June 2019

Background:

There is substantial variation in breast cancer survival rates, even among patients with similar clinical and genomic profiles. New biomarkers are needed to improve risk stratification and inform treatment options. Our aim was to identify novel miRNAs associated with breast cancer survival and quantify their prognostic value after adjusting for established clinical factors and genomic markers.

Methods:

Using the Women's Healthy Eating and Living (WHEL) breast cancer cohort with >15 years of follow-up and archived tumor specimens, we assayed PAM50 mRNAs and 25 miRNAs using the Nanostring nCounter platform.

Results:

We obtained high-quality reads on 1,253 samples (75% of available specimens) and used an existing research-use algorithm to ascertain PAM50 subtypes and risk scores (ROR-PT). We identified miRNAs significantly associated with breast cancer outcomes and then tested these in independent TCGA samples. miRNAs that were also prognostic in TCGA samples were further evaluated in multiple regression Cox models. We also used penalized regression for unbiased discovery.

Conclusions:

Two miRNAs, 210 and 29c, were associated with breast cancer outcomes in the WHEL and TCGA studies and further improved risk stratification within PAM50 risk groups: 10-year survival was 62% in the node-negative high miR-210-high ROR-PT group versus 75% in the low miR-210- high ROR-PT group. Similar results were obtained for miR-29c. We identified three additional miRNAs, 187-3p, 143-3p, and 205-5p, via penalized regression.

Impact:

Our findings suggest that miRNAs might be prognostic for long-term breast cancer survival and might improve risk stratification. Further research to incorporate miRNAs into existing clinicogenomic signatures is needed.
Longitudinal Changes in Volumetric Breast Density in Healthy Women across the Menopausal Transition
Authors: Engmann Natalie J. , Scott Christopher , Jensen Matthew R. , Winham Stacey J. , Ma Lin , Brandt Kathleen R. , Mahmoudzadeh Amir , Whaley Dana H. , Hruska Carrie B. , Wu Fang-Fang , Norman Aaron D. , Hiatt Robert A. , Heine John , Shepherd John , Pankratz V. Shane , Miglioretti Diana L. , Kerlikowske Karla , Vachon Celine M.
Published: June 2019

Background:

Mammographic breast density declines during menopause. We assessed changes in volumetric breast density across the menopausal transition and factors that influence these changes.

Methods:

Women without a history of breast cancer, who had full field digital mammograms during both pre- and postmenopausal periods, at least 2 years apart, were sampled from four facilities within the San Francisco Mammography Registry from 2007 to 2013. Dense breast volume (DV) was assessed using Volpara on mammograms across the time period. Annualized change in DV from pre- to postmenopause was estimated using linear mixed models adjusted for covariates and per-woman random effects. Multiplicative interactions were evaluated between premenopausal risk factors and time to determine whether these covariates modified the annualized changes.

Results:

Among the 2,586 eligible women, 1,802 had one premenopausal and one postmenopausal mammogram, 628 had an additional perimenopausal mammogram, and 156 had two perimenopausal mammograms. Women experienced an annualized decrease in DV [−2.2 cm3 (95% confidence interval, −2.7 to −1.7)] over the menopausal transition. Declines were greater among women with a premenopausal DV above the median (54 cm3) versus below (DV, −3.5 cm3 vs. −1.0 cm3; P < 0.0001). Other breast cancer risk factors, including race, body mass index, family history, alcohol, and postmenopausal hormone therapy, had no effect on change in DV over the menopausal transition.

Conclusions:

High premenopausal DV was a strong predictor of greater reductions in DV across the menopausal transition.

Impact:

We found that few factors other than premenopausal density influence changes in DV across the menopausal transition, limiting targeted prevention efforts.
Detection of NRG1 Fusions in Solid Tumors: Rare Gold?
Authors: Dimou Anastasios , Camidge D. Ross
Published: June 2019

Fusions between NRG1 and partner genes are rare, tumorigenic genomic events occurring in patients with lung and other cancers, associated with activation of ERBB2/ERBB3 heterodimers. Inhibition of ERBB2 and/or ERBB3 in this group of patients is a promising strategy in clinical trials.

See related article by Jonna et al., p. 4966
NT-proBNP and Echocardiographic Parameters in Liver Cirrhosis: Correlations with Disease Severity
Authors: Mihailovici Alexandru Radu , Donoiu Ionuț , Gheonea Dan Ionuț , Mirea Oana , Târtea Georgică Costinel , Buşe Maria , Calborean Veronica , Obleagă Cosmin , Pădureanu Vlad , Istrătoaie Octavian
Published: June 2019

Objective: Liver cirrhosis is associated with several cardiovascular abnormalities including a hyperdynamic splanchnic and systemic circulation related to arterial vasodilatation, finally leading to sodium retention, central hypovolemia, and increased intravascular volume. The objective of this study was to evaluate the relationship between NT-proBNP and echocardiographic parameters and liver disease stage in patients with cirrhosis. Method: This prospective study included 82 consecutive patients diagnosed with liver cirrhosis and 120 healthy, age- and sex-matched subjects. Standard transthoracic echocardiography was performed in all patients. Plasma NT-proBNP levels were determined. Liver disease severity in patients with cirrhosis was established by Child-Pugh class, MELD score and presence/absence of ascites. Results: Plasma levels of NT-proBNP were significantly higher in cirrhotic patients than the corresponding levels in the healthy subjects. NT-proBNP levels were also significantly elevated in Child-Pugh class C patients compared to those in class B and A. Left atrium (LA) size, diastolic function, left ventricular (LV) wall thickness, and LV ejection fraction were significantly altered in cirrhotic patients compared to controls. Advanced cirrhosis and high levels of NT-proBNP were significantly associated with increased LA volume and signs of cardiac diastolic dysfunction. We also observed significant differences between quartile groups of MELD score for the following: NT-proBNP, Troponin I, LA volume, left ventricle wall thickness, lateral wall and septum systolic tissue Doppler velocities and global longitudinal strain. Conclusion: NT-proBNP is increased in patients with cirrhosis and is correlated with the severity of liver disease as established by Child-Pugh class, MELD score, and the presence of ascites.
Relationship between History of Ischemic Stroke and All-Cause Mortality in Incident Dialysis Patients
Authors: Kojima Masayasu , Inaguma Daijo , Koide Shigehisa , Koshi-Ito Eri , Takahashi Kazuo , Hayashi Hiroki , Tsuboi Naotake , Hasegawa Midori , Yuzawa Yukio
Published: June 2019

Background: Few studies have focused on the association between history of ischemic stroke at predialysis stage and mortality after dialysis initiation. Objective: To examine whether history of stroke in incident dialysis patients is associated with mortality, including all-cause and cardiovascular (CV)-related mortality. Methods: The study database was derived from the Aichi Cohort Study of Prognosis in Patients Newly Initiated into Dialysis, a multicenter, prospective, cohort analysis. We classified patients into 2 groups according to their history of ischemic stroke and compared their outcomes. Propensity scores (PSs) represented the probability of being assigned to a group with or without a history of ischemic stroke. We defined the following outcomes: all-cause mortality; CV-related mortality; non-CV-related mortality; infection-related mortality; and stroke event after dialysis initiation. Factors contributing to the outcomes were examined using stepwise multivariate Cox proportional hazards analysis. Results: All-cause mortality was significantly higher in the ischemic stroke group (log-rank test p < 0.001). All-cause, non-CV-related, and infection-related mortality and stroke event after dialysis initiation were significantly higher in the ischemic stroke group after PS matching (log-rank test: p < 0.001, <0.001, 0.002, and 0.002, respectively). History of ischemic stroke was associated with all-cause mortality in univariate analysis (hazard ratio [HR] 1.85, 95% CI 1.44–2.37). History of ischemic stroke before dialysis initiation was associated with all-cause mortality in multivariate analysis (HR 1.39, 95% CI 1.05–1.85). Conclusion: The present study revealed that history of ischemic stroke before dialysis initiation was associated with all-cause, non-CV-related, and infection-related mortality and stroke event after dialysis initiation during maintenance dialysis.
Prevalence and Risk Factors of Cerebral Microbleeds in Patients with Nonvalvular Atrial Fibrillation: An Enhanced T2*-Weighted Angiography Imaging Study
Authors: Li Zhiqiang , Cao Lu , Dong Wanqing , Zhang Jianping , Wang Chunyu , He Xianjun , Huang Wenqi , Li Yuzhou , Zhao Ming
Published: June 2019

Background/Aims: Cerebral microbleeds (CMBs) may predict the occurrence of intracerebral hemorrhage (ICH). Warfarin use may cause ICH. It is still controversial whether warfarin increases CMBs in atrial fibrillation (AF) patients. The study aimed to investigate the prevalence of CMBs and risk factors in AF patient population. Methods: This single retrospective center study included 113 patients with nonvalvular atrial fibrillation (NVAF) who were on outpatient treatment. CMBs were counted using 3D-enhanced T2*-weighted angiography (ESWAN) imaging. We compared clinical and radiological data between patients who used warfarin and not used warfarin with univariate analysis. The associations between clinical and radiological data and CMBs in NVAF population were analyzed with multivariate linear regression analyses. Results: Among 113 NVAF patients, CMBs were found in 33 (29.2%) patients; there were 53 patients who used warfarin for thromboembolism prevention and 60 patients with similar demographic features who did not use warfarin. CMBs on ESWAN MRI showed no significant difference between the 2 groups (p = 0.061). Patients with CMBs were older than patients without CMBs (p = 0.046), and the frequency of smokers (p = 0.028), hypertension (p = 0.029), previous ICH (p = 0.000), and leukoaraiosis (p = 0.020) in patients with CMBs were significantly higher than patients without CMBs. In multivariate linear regression analyses, previous ICH (β = 1.438, p = 0.000), age (β = 0.082, p = 0.000), hypertension (β = 0.956 p = 0.003), warfarin treatment (β = 0.849, p = 0.006), and smokers (β = 0.920, p = 0.016) were positive linear predictors of CMBs number levels in NVAF patients. Conclusion: The present data demonstrated that CMBs were associated with age, hypertension, warfarin treatment, smoking, and a history of ICH. We also found neither CHA2DS2-VASc score nor HAS-BLED score was associated with CMBs in patients with NVAF.
Preimplant Phosphodiesterase-5 Inhibitor Use Is Associated With Higher Rates of Severe Early Right Heart Failure After Left Ventricular Assist Device Implantation
Authors: Gulati Gaurav , Grandin E. Wilson , Kennedy Kevin , Cabezas Fausto , DeNofrio David D. , Kociol Robb , Rame J. Eduardo , Pagani Francis D. , Kirklin James K. , Kormos Robert L. , Teuteberg Jeffrey , Kiernan Michael
Published: June 2019

Background:

Early right heart failure (RHF) occurs commonly in left ventricular assist device (LVAD) recipients, and increased right ventricular (RV) afterload may contribute. Selective pulmonary vasodilators, like phosphodiesterase-5 inhibitors (PDE5i), are used off-label to reduce RV afterload before LVAD implantation, but the association between preoperative PDE5i use and early RHF after LVAD is unknown.

Methods and Results:

We analyzed adult patients from the INTERMACS registry (Interagency Registry for Mechanically Assisted Circulatory Support) who received a continuous flow LVAD after 2012. Patients on PDE5i were propensity-matched 1:1 to controls. The primary outcome was the incidence of severe early RHF, defined as the composite of death from RHF within 30 days, need for RV assist device support within 30 days, or use of inotropes beyond 14 days. Of 11 544 continuous flow LVAD recipients, 1199 (10.4%) received preoperative PDE5i. Compared to controls, patients on PDE5i had higher pulmonary artery systolic pressure (53.4 mm Hg versus 49.5 mm Hg) and pulmonary vascular resistance (2.6 WU versus 2.3 WU;
P
<0.001 for both). Before propensity matching, the incidence of severe early RHF was higher among patients on PDE5i than in controls (29.4% versus 23.1%; unadjusted odds ratio (OR), 1.32; 95% CI, 1.17–1.50). This association persisted after propensity matching (PDE5i, 28.9% versus control 23.7%; OR, 1.31; 95% CI, 1.09–1.57), driven by a higher incidence of prolonged inotropic support. Similar results were observed across a wide range of subgroups stratified by markers of pulmonary vascular disease and RV dysfunction.

Conclusions:

Patients treated with preoperative PDE5i had markers of increased RV afterload and HF severity compared to unmatched controls. Even after propensity matching, patients receiving preimplant PDE5i therapy had higher rates of post-LVAD RHF.