bluuebunny/crossref_metadata_2025 huggingface dataset:
Coronary sinus reducer implantation in the middle cardiac vein for the treatment of refractory angina
Authors: D'Amico Gianpiero , Massussi Mauro , Fraccaro Chiara , Tarantini Giuseppe
Published: November 2019

Coronary sinus Reducer is a current therapeutic treatment for patients with persistent refractory angina. We report a case of successful implantation of the device in the middle cardiac vein of a 65 years old female patient. The singular and unusual site for the Reducer was planned after a careful assessment of the venous drainage of the ischemic territory.
Lower urine sodium predicts longer length of stay in acute heart failure patients: Insights from the ROSE AHF trial
Authors: Cunningham Jonathan W. , Sun Jie‐Lena , Mc Causland Finnian R. , Ly Samantha , Anstrom Kevin J. , Lindenfeld Joann , Givertz Michael M. , Stevenson Lynne W. , Lakdawala Neal K.
Published: November 2019

Background

In patients hospitalized with acute heart failure (AHF), low urine sodium concentration (UNa) after diuretic treatment may identify patients at risk for longer length of stay (LOS) and adverse events. We investigated the prognostic significance of 24‐hour cumulative postdiuretic urine sodium concentration in a multicenter clinical trial population.

Methods

The Renal Optimization Strategies Evaluation AHF (ROSE AHF) trial randomized 360 patients with AHF and renal dysfunction receiving intravenous diuretic to dopamine, nesiritide, or placebo. Sodium concentration was measured in cumulative urine sample collected during the first 24 hours after randomization in 298 patients. Based on prior studies, lower UNa was defined as ≤60 mmol/L.

Results

Lower UNa was present in 142 (48%) patients, who had longer LOS (7 days vs 5 days, P < .001) and less 72‐hour weight loss (5.7 lb vs 9.0 lb, P < .001). These associations persisted after controlling for baseline estimated glomerular filtration rate and outpatient furosemide dose. Lower UNa did not modify the null effects of dopamine or nesiritide on clinical outcomes. Results were similar for spot rather than cumulative 24‐hour UNa concentration.

Conclusion

In patients hospitalized for AHF and renal dysfunction, UNa ≤ 60 mmol/L during the first 24 hours of diuresis identifies patients at risk for prolonged hospitalization but does not provide an indication for adjunctive dopamine or nesiritide.
Rising incidence of late‐stage head and neck cancer in the United States
Authors: Thompson‐Harvey Adam , Yetukuri Mahi , Hansen Alec R. , Simpson Matthew C. , Adjei Boakye Eric , Varvares Mark A. , Osazuwa‐Peters Nosayaba
Published: November 2019

Background

The current study was conducted to determine whether the incidence of late‐stage head and neck cancer (HNC) is decreasing and to estimate the risk of late‐stage HNC diagnosis based on race and sex.

Methods

Age‐adjusted incidence rates for patients aged ≥18 years with stage IV HNC were abstracted from the Surveillance, Epidemiology, and End Results database (2004‐2015). Rates were stratified by race, sex, and age. Joinpoint regression estimated annual percent changes (APCs) in rates over time, and logistic regression estimated adjusted odds ratios (aORs).

Results

There were 57,118 patients with stage IV HNC in the current study cohort, with an average age of 61.9 years. From 2004 to 2015, the age‐adjusted incidence rates for stage IV HNC significantly increased by 26.1% (6.11 per 100,000 person‐years in 2004 to 7.70 per 100,000 person‐years in 2015). White and Asian/Pacific Islander/American Indian/Alaska Native patients had significant increases in incidence (APC for white patients, 3.03 [P < .01] and APC for other races, 1.95 [P < .01]), whereas rates among black patients remained stable but were highest across racial groups. Incidence was higher among males compared with females. When restricted only to patients with stage IVC (metastatic) HNC, there remained a significant increase in incidence, especially for oropharyngeal cancer, which showed a 22.9% increase (0.21 per 100,000 person‐years in 2004 vs 0.25 per 100,000 person‐years in 2015). Despite a decreasing overall incidence of stage IV HNC in black patients (aOR, 1.28; 95% CI, 1.22‐1.34) they, along with males (aOR, 3.95; 95% CI, 3.80‐4.11), had significantly increased risks of being diagnosed with late‐stage HNC.

Conclusions

There is an increasing incidence of late‐stage HNC in the United States, with male patients and black individuals faring the worst.
Oral status of HIV‐infected children aged 12 years or younger who attended a Paediatric Infectious Diseases Clinic in Cape Town
Authors: Mohamed Nadia , Mathiba Olorato Patience , Mulder Riaan
Published: November 2019

Background

Children continue to suffer from the impact of the human immunodeficiency virus‐acquired immunodeficiency syndrome (HIV/AIDS) pandemic. In Cape Town, these children receive medical care including antiretroviral therapy from facilities like Tygerberg Hospital's Paediatric Infectious Diseases Clinic. HIV‐infected children may experience an increased caries experience when compared with their healthy peers.

Aim

The aim of this study was to determine the oral health status of HIV‐infected children younger than 12 years receiving antiviral drugs at the Paediatric Infectious Diseases Clinic.

Design

A cross‐sectional survey was conducted among children aged between 2 and 12 years presenting at this clinic. Caregivers were interviewed to obtain information regarding health seeking behaviour, oral hygiene practices and dietary habits. A single clinician undertook a standardized clinical intraoral examination according to the World Health Organization guidelines, with modifications.

Results

Sixty‐six children were recruited. A high prevalence of dental caries (78.8%) and an unmet treatment need of 90.4% were recorded among the participants. Most children had never visited the dentist, and those who did had mainly received emergency dental care.

Conclusion

The high prevalence of severe dental caries in this population highlights the need for oral health awareness and the inclusion of oral health care in the comprehensive care of children with HIV.

Why this paper is important to paediatric dentists

The study highlights the importance of collaborating with health professions outside of dentistry.

Doctors and nurses are often the first health professionals to come into contact with children with special needs. They should therefore be made aware of the early signs of decay so that these patients can be referred for dental treatment timeously.

Holistic management of children with special healthcare needs is essential to improve their overall well‐being.
What colour is the corporate social responsibility report? Structural visual rhetoric, impression management strategies, and stakeholder engagement
Authors: García‐Sánchez Isabel‐María , Araújo‐Bernardo Cristina‐Andrea
Published: November 2019

This paper analyses the level of managerial discretion in the practice of disclosing social and environmental information using impression management techniques based on visual rhetoric and associated with the structural dimension of the size of graphics and photographs and the colour of these images and of the animations in the report. From a sample of 105 non‐financial information statements from the 35 Spanish companies that were part of the IBEX 35 in 2018, 2017, and 2013, the results suggest two different impression management strategies used by companies to manage stakeholder's perception, with specific features at the industry level and with different levels of divergence/convergence in the structural dimensions of size or colour according to the level of standardisation in the revealed information.
Q2ABR: QoE‐aware adaptive video bit rate solution
Authors: Amour Lamine , Souihi Sami , Mellouk Abdelhamid , Mushtaq S.M.
Published: November 2019

In this paper, we propose a new adaptive bit rate (ABR) streaming method. This method is based on estimating and monitoring users' video streaming experience, their quality of experience (QoE). This ensures a good user QoE and optimises bandwidth utilisation by monitoring video buffer fill rate to ensure minimal data traffic. First, we achieve a QoE evaluation model based on network bandwidth, video segment representation, and dropped video frame rate parameters. Second, following our QoE evaluation model, we formulate an ABR method using the reinforcement learning (RL) paradigm to select video representations and using a breakpoint detection mechanism to monitor end‐user QoE variation. The proposed ABR method is called “QoE‐aware adaptive bit rate (Q2ABR)” and is composed of three individual modules, one for QoE estimation using machine learning methods, one for QoE variation monitoring using the breakpoint detection mechanism, and one for video representation selection using reinforcement learning. The design objective of Q2ABR is to ensure the overall QoE of these users while maintaining a minimum variation in the standard deviation of the users' QoE values. Third, the performance of the Q2ABR method is evaluated and compared with several existing ABR approaches in the literature using real traces that we collect on different transport scenarios (such as bus and train, among others). Since this method considers the user's perception of video quality as a regulator for optimising the overall video distribution network, good results are ensured in terms of the user's experience and buffer fill rate.
OMS: Opportunistic mules for short latency data collection in smart cities
Authors: Chehbour Fairouz , Doukha Zouina , Moussaoui Samira , Guerroumi Mohamed
Published: November 2019

In smart city scenarios, data collected by sensors are required to be conveyed to central controllers for processing. Thus, efficient data collection mechanisms considering the urban environment characteristics should take place. To that end, the data mules approach is proved to be efficient. However, being applied to urban environment leads to high data delivery latency due to the characteristics of this environment. Motivated by the need to reduce the collection latency of such an approach, we propose to provide each road segment with a data mule to create a process of distributed data collection. Our scheme leverages opportunistic inter‐vehicular communications for assigning the mule role to adequate vehicles. The simulation in realistic mobility settings reveals that our scheme can provide more than 80% of the area of interest with data mules in less than 1 minute. In addition, the data collection latency can be reduced from 24 hours to few minutes.
A microfacies analysis of arid continental carbonates from the Cedar Mesa Sandstone Formation, Utah, USA
Authors: Pettigrew Ross P. , Rogers Steven L. , Clarke Stuart M.
Published: November 2019

Arid continental environments are typically dominated by siliciclastic aeolian, alluvial and fluvial deposits. Despite their common recognition within these environments, carbonate deposits are often overlooked, yet they can provide vital insight into the depositional history, climate and tectonic controls of a sedimentary basin. This work presents a detailed microfacies analysis of the carbonates found within the Cedar Mesa Sandstone Formation of the Western USA. The Cedar Mesa Sandstone Formation is an early Permian, predominantly aeolian succession, exposed across much of the Colorado Plateau of southern Utah and northern Arizona. The formation is dominantly clastic erg deposits, that grade into a mixed carbonate/clastic sedimentary succession interbedded with carbonate and evaporitic units, interpreted to represent sabkha or sabkha‐like deposits. While many authors have worked within the aeolian dominated facies and have proposed various facies schemes for the siliciclastic components, comparatively little attention has been paid to the mixed evaporitic/clastic/carbonate aeolian‐sabkha transition zone. In this work the microfacies of the carbonates present within the Cedar Mesa Sandstone are analysed, in order to: (a) develop a record of, and interpret carbonate components, (b) propose depositional mechanisms and (c) identify evolutionary trends that stand alongside the formation's clastic depositional story. Six microfacies are presented: (MF1) Clastic Influenced Carbonate Wackestone; (MF2) Laminated Carbonate Wackestone/Packstone; (MF3) Microbial Laminated Fenestral Bindstone; (MF4) Rounded Mudclast Wackestone; (MF5) Laminated Bioclastic‐Ostracod‐Carbonate Wackestone and (MF6) Microcrystalline Quartz. The microfacies have been interpreted to document the development of carbonate interdune, lacustrine and continental sabkha environments influenced by localized fault control juxtaposed across a wetting and drying climate cycle and provide useful comparisons for other mixed evaporite/carbonate and clastic sequences.
Circadian‐timed quick‐release bromocriptine lowers elevated resting heart rate in patients with type 2 diabetes mellitus
Authors: Chamarthi Bindu , Vinik Aaron , Ezrokhi Michael , Cincotta Anthony H.
Published: November 2019

Objective

Sympathetic nervous system (SNS) overactivity is a risk factor for insulin resistance and cardiovascular disease (CVD). We evaluated the impact of bromocriptine‐QR, a dopamine‐agonist antidiabetes medication, on elevated resting heart rate (RHR) (a marker of SNS overactivity in metabolic syndrome), blood pressure (BP) and the relationship between bromocriptine‐QR's effects on RHR and HbA1c in type 2 diabetes subjects.

Design and Subjects

RHR and BP changes were evaluated in this post hoc analysis of data from a randomized controlled trial in 1014 type 2 diabetes subjects randomized to bromocriptine‐QR vs placebo added to standard therapy (diet ± ≤2 oral antidiabetes medications) for 24 weeks without concomitant antihypertensive or antidiabetes medication changes, stratified by baseline RHR (bRHR).

Results

In subjects with bRHR ≥70 beats/min, bromocriptine‐QR vs placebo reduced RHR by −3.4 beats/min and reduced BP (baseline 130/79; systolic, diastolic, mean arterial BP reductions [mm Hg]: −3.6 [P = .02], −1.9 [P = .05], −2.5 [P = .02]). RHR reductions increased with higher baseline HbA1c (bHbA1c) (−2.7 [P = .03], −5 [P = .002], −6.1 [P = .002] with bHbA1c ≤7, >7, ≥7.5%, respectively] in the bRHR ≥70 group and more so with bRHR ≥80 (−4.5 [P = .07], −7.8 [P = .015], −9.9 [P = .005]). Subjects with bRHR <70 had no significant change in RHR or BP. With bHbA1c ≥7.5%, %HbA1c reductions with bromocriptine‐QR vs placebo were −0.50 (P = .04), −0.73 (P = .005) and −1.22 (P = .008) with bRHR <70, ≥70 and ≥80, respectively. With bRHR ≥70, the magnitude of bromocriptine‐QR‐induced RHR reduction was an independent predictor of bromocriptine‐QR's HbA1c lowering effect.

Conclusion

Bromocriptine‐QR lowers elevated RHR with concurrent decrease in BP and hyperglycaemia. These findings suggest a potential sympatholytic mechanism contributing to bromocriptine‐QR's antidiabetes effect and potentially its previously demonstrated effect to reduce CVD events.
Troponins and brain natriuretic peptides for the prediction of cardiotoxicity in cancer patients: a meta‐analysis
Authors: Michel Lars , Mincu Raluca I. , Mahabadi Amir A. , Settelmeier Stephan , Al‐Rashid Fadi , Rassaf Tienush , Totzeck Matthias
Published: November 2019

Aims

Cardiac biomarkers are a mainstay in diagnosis of cardiovascular disease but their role in cardio‐oncology has not yet been systematically evaluated. This meta‐analysis aims to determine whether cardiac troponins and (N‐terminal pro) brain natriuretic peptide (BNP/NT‐proBNP) predict cancer therapy‐related left ventricular (LV) dysfunction.

Methods and results

Scientific databases were searched for studies that assessed troponins or BNP/NT‐proBNP in adult patients undergoing cancer therapy. Data from 61 trials with 5691 patients were included. Cancer therapy was associated with an increase in troponin levels [odds ratio (OR) 14.3, 95% confidence interval (CI) 6.0–34.1; n = 3049]. Patients with elevated troponins receiving chemotherapy or human epidermal growth factor receptor 2 inhibitor therapy were at higher risk for LV dysfunction (OR 11.9, 95% CI 4.4–32.1; n = 2163). Troponin had a negative predictive value of 93%. Mean BNP/NT‐proBNP levels were increased in patients post‐treatment (standardized mean difference 0.6, 95% CI 0.3–0.9; n = 912), but the available evidence did not consistently indicate prediction of LV dysfunction (OR 1.7, 95% CI 0.7–4.2; n = 197). β‐blocker and angiotensin‐converting enzyme inhibitor therapy to mitigate cardiotoxicity during cancer therapy was associated with a decline in serum troponins (OR 4.1, 95% CI 1.7–9.8; n = 466).

Conclusion

Elevated troponin levels predict LV dysfunction in patients receiving cancer therapy. Assessment of troponin levels may qualify as a screening test to identify patients who require referral to cardio‐oncology units and benefit from preventive strategies. Further evidence is required for both biomarkers.
Anti‐TNF treatment negatively regulates human CD4+ T‐cell activation and maturation in vitro, but does not confer an anergic or suppressive phenotype
Authors: Povoleri Giovanni A. M. , Lalnunhlimi Sylvine , Steel Kathryn J. A. , Agrawal Shweta , O'Byrne Aoife M. , Ridley Michael , Kordasti Shahram , Frederiksen Klaus S. , Roberts Ceri A. , Taams Leonie S.
Published: November 2019

TNF‐blockade has shown clear therapeutic value in rheumatoid arthritis and other immune‐mediated inflammatory diseases, however its mechanism of action is not fully elucidated. We investigated the effects of TNF‐blockade on CD4+ T cell activation, maturation, and proliferation, and assessed whether TNF‐inhibitors confer regulatory potential to CD4+ T cells. CyTOF and flow cytometry analysis revealed that in vitro treatment of human CD4+ T cells with the anti‐TNF monoclonal antibody adalimumab promoted IL‐10 expression in CD4+ T cells, whilst decreasing cellular activation. In line with this, analysis of gene expression profiling datasets of anti‐TNF‐treated IL‐17 or IFN‐γ‐producing CD4+ T cells revealed changes in multiple pathways associated with cell cycle and proliferation. Kinetics experiments showed that anti‐TNF treatment led to delayed, rather than impaired T‐cell activation and maturation. Whilst anti‐TNF‐treated CD4+ T cells displayed some hyporesponsiveness upon restimulation, they did not acquire enhanced capacity to suppress T‐cell responses or modulate monocyte phenotype. These cells however displayed a reduced ability to induce IL‐6 and IL‐8 production by synovial fibroblasts. Together, these data indicate that anti‐TNF treatment delays human CD4+ T‐cell activation, maturation, and proliferation, and this reduced activation state may impair their ability to activate stromal cells.
Lithium Complexes with Bridging and Terminal NHC Ligands: The Decisive Influence of an Anionic Tether
Authors: Evans Kieren J. , Campbell Cameron L. , Haddow Mairi F. , Luz Christian , Morton Paul A. , Mansell Stephen M.
Published: November 2019

Deprotonation of the fluorenyl‐tethered imidazolinium salt [9‐(C13H9)C2H4N(CH)C2H4N(2,4,6‐Me3C6H2)][BF4] gave a spirocyclic compound that reacted with a synergic mixture of LiPh/LiN(SiMe3)2 or LinBu/LiN(SiMe3)2 to give a dilithium complex incorporating a bridging N(SiMe3)2 ligand. In contrast, deprotonation of the imidazolium salt [9‐(C13H9)C2H4N(CH)C2H2N(Me)][Br] instead yielded the free NHC, which reacted with nBuLi to form a dimeric, NHC‐bridged dilithium complex. Addition of LiN(SiMe3)2 led to coordination and the formation of a dilithium complex with a bridging N(SiMe3)2 ligand, which was characterised in the solid state as a 1D coordination polymer. The reaction of 1,3‐bis(2,6‐diisopropylphenyl)‐4,5‐dihydroimidazol‐2‐ylidene (SIPr) with lithium indenide and lithium fluorenide gave soluble species with terminal binding of the NHC to the lithium cation and η5 coordination of indenyl or fluorenyl. A symmetrical bridging mode for an NHC donor was therefore observed only if a tethered fluorenyl anion was present with no additional amide ligand.
Bimetallic Oxide Hollow Structures Induced by Surface Coordination of ZIF‐67
Authors: Zhao Kaixuan , Guo Jinxin , Wei Huiying , Yang Yanzhao
Published: November 2019

Bimetallic hollow nanomaterials which are composed of two different metal/metal oxide materials show great potentials owing to their unique structural features. Here, the second metal ions were introduced into the surface of ZIF‐67 by ultrasonication to form bimetallic hollow complexes, and the coordination between the second metal ions and ZIF‐67 colloidal crystals are further investigated. A series of bimetallic complexes has been synthesized by incorporating FeIII, CuII and NiII into the coordinating block of ZIF‐67. After calcination in oxygen, these as‐prepared transformed to Fe/Cu/Ni doped Co3O4 hollow nanoboxes. We found a facile and general method to form bimetallic complexes by complexing the second metal ions with ZIF‐67 surface ligands and calcining to form bimetallic hollow nanoboxes.
Amine‐Functionalized Spin Crossover Building Blocks
Authors: Flötotto Henrik , Secker Tim , Kögerler Paul , Besson Claire
Published: November 2019

Invited for the cover of this issue is the group of Paul Kögerler from RWTH Aachen University, Germany. The cover image shows an aluminum sheet painted with thermochromic lacquer based on functionalized derivatives of iron(II) bis(tris(pyrazolyl)borate) complexes.
Lamellar V5O12·6H2O Nanobelts Coupled with Inert Zn(OH)2·0.5H2O as Cathode for Aqueous Zn2+/Nonaqueous Na+ Storage Applications
Authors: Yan Honglin , Ru Qiang , Gao Ping , Cheng Shikun , Chen Fuming , Ling Francis Chi-Chung , Wei Li
Published: November 2019

Lamellar V5O12·6H2O nanobelts coupled with inert Zn(OH)2·0.5H2O are in situ fabricated via a facile hydrothermal strategy. Herein, the inert Zn(OH)2·0.5H2O phase acts as a buffer matrix to strengthen the structural stability of V5O12·6H2O host material, relieving the severe volume variation. Therefore, benefiting from the large interplanar spacing of active V5O12·6H2O and volume buffering effect of inert Zn(OH)2·0.5H2O, V5O12·6H2O/Zn(OH)2·0.5H2O hybrid (denoted as Z‐V5O12·6H2O) sustainably endures the repetitive Zn2+/Na+ insertion/extraction and boosts the electrochemical properties. As cathodes for aqueous zinc‐ion batteries, the Z‐V5O12·6H2O hybrid shows a high discharge capacity of 328 mAh g−1 at 50 mA g−1 and keeps 146 mAh g−1 at 1 A g−1 after 1000 cycles. For nonaqueous sodium‐ion batteries, the hybrid also furnishes a high initial discharge capacity of 241 mAh g−1 at a current density of 50 mA g−1 and maintains 97 mAh g−1 at 100 mA g−1 after 100 cycles.
The Flavor Enhancer Maltol Increases Pigment Aggregation in Dermal and Neural Melanophores in Xenopus laevis Tadpoles
Authors: Dahora Lara I. , Fitzgerald Ashley , Emanuel Matthew , Baiges Alexa F. , Husain Zahabiya , Thompson Christopher K.
Published: November 2019

Melanophores are pigmented cells that change the distribution of melanosomes, enabling animals to appear lighter or darker for camouflage, thermoregulation, and protection from ultraviolet radiation. A complex series of hormonal and neural mechanisms regulates melanophore pigment distribution, making these dynamic cells a valuable tool to screen toxicants as they rapidly respond to changes in the environment. We found that maltol, a naturally occurring flavor enhancer and fragrance agent, induces melanophore pigment aggregation in a dose-dependent manner in Xenopus laevis tadpoles. To determine if maltol affects camouflage adaptation, we placed tadpoles into maltol baths situated over either a white or a black background. Maltol induced pigment aggregation in a similar dose-dependent pattern regardless of background color. We also tested how maltol treatment compares to melatonin treatment and found that the degree of pigment aggregation induced by maltol is similar to treatment with melatonin but that maltol induces over a much longer time course. Last, maltol had no effect on mRNA expression in the brain of genes that regulate camouflage-related pigment aggregation. The present results suggest that maltol does not exert its effects via the camouflage adaptation mechanism or via melatonin-related mechanisms. These results are the first to identify a putative toxicological effect of maltol exposure in vivo and rule out several mechanisms by which maltol may exert its effects on pigment aggregation. Environ Toxicol Chem 2020;39:381–395. © 2019 SETAC
Primates got personality, too: Toward an integrative primatology of consistent individual differences in behavior
Authors: Blaszczyk Maryjka B.
Published: November 2019

In recent years, research on animal personality has exploded within the field of behavioral ecology. Consistent individual differences in behavior exist in a wide range of species, and these differences can have fitness consequences and influence several aspects of a species' ecology. In comparison to studies of other animals, however, there has been relatively little research on the behavioral ecology of primate personality. This is surprising given the large body of research within psychology and biomedicine showing that primate personality traits are heritable and linked to health and life history outcomes. In this article, I bring together theoretical perspectives on the ecology and evolution of animal personality with an integrative review of what we know about primate personality from studies conducted on captive, free‐ranging, and wild primates. Incorporating frameworks that emphasize consistency in behavior into primate behavioral ecology research holds promise for improving our understanding of primate behavioral evolution.
Domain decomposition methods in a geometrical multiscale domain using finite volume schemes
Authors: Viallon Marie‐Claude
Published: November 2019

The heat equation is solved by using a finite volume discretization in a domain that consists of a two‐dimensional central node and several one‐dimensional outgoing branches. Several interface connection options to match the submodels set on the node and on the branches, with or without continuity, are looked at. For each of them, a monolithic scheme is defined, and existence and uniqueness of the solution is proved. New schemes are deduced, which are obtained through domain decomposition methods in the form of interface systems, with one or two unknowns per interface. A comparative systematic study is carried out from an algebraic and numerical point of view according to the interface conditions: Dirichlet, Neumann, or Robin. An efficient diagonal preconditioning is proposed.
A high‐order compact scheme for solving the 2D steady incompressible Navier‐Stokes equations in general curvilinear coordinates
Authors: Chen Jinqiang , Yu Peixiang , Tian Zhen F. , Ouyang Hua
Published: November 2019

In this paper, a high‐order compact finite difference algorithm is established for the stream function‐velocity formulation of the two‐dimensional steady incompressible Navier‐Stokes equations in general curvilinear coordinates. Different from the previous work, not only the stream function and its first‐order partial derivatives but also the second‐order mixed partial derivative is treated as unknown variable in this work. Numerical examples, including a test problem with an analytical solution, three types of lid‐driven cavity flow problems with unusual shapes and steady flow past a circular cylinder as well as an elliptic cylinder with angle of attack, are solved numerically by the newly proposed scheme. For two types of the lid‐driven trapezoidal cavity flow, we provide the detailed data using the fine grid sizes, which can be considered the benchmark solutions. The results obtained prove that the present numerical method has the ability to solve the incompressible flow for complex geometry in engineering applications, especially by using a nonorthogonal coordinate transformation, with high accuracy.
CO2 capture and mineralization using carbide slag doped fly ash
Authors: Liu Rong , Wang Xiaolong , Gao Shiwang
Published: November 2019

A novel direct gas–solid mineral carbonation process using carbide slag doped fly ash to capture and mineralize CO2 from flue gas was developed to overcome the barriers of long reaction time and large reactor size from aqueous processes. A laboratory‐scale fixed bed reactor with a thermogravimetric analyser and a pilot‐scale circulating entrained‐flow bed (CEB) rector system were constructed to investigate the intensification method and reaction parameters. The carbonation efficiency (ζCa [%]) was improved four times by carbide slag doped fly ash in a semi‐dry atmosphere; thus, the active calcium hydroxide from carbide slag and fly ash can react with CO2 in a thin liquid film through an ionic reaction route. The key reaction parameters, such as temperature, steam addition and water injection, were studied to promote Ca(OH)2 formation and to facilitate CO2 diffusion. As a result of the pilot‐scale experiment, carbonation efficiency achieved a maximum value of 55% with 15% steam addition in the feed and 6 kg h–1 water injection into CEB at 550 °C. © 2019 Society of Chemical Industry and John Wiley & Sons, Ltd.
Immunosuppression Withdrawal in Liver Transplant Recipients on Sirolimus
Authors: Levitsky Josh , Burrell Bryna E. , Kanaparthi Sai , Turka Laurence A. , Kurian Sunil , Sanchez‐Fueyo Alberto , Lozano Juan J. , Demetris Anthony , Lesniak Andrew , Kirk Allan D. , Stempora Linda , Yang Guang‐Yu , Mathew James M.
Published: November 2019

BACKGROUND AND AIMS

As conversion from calcineurin inhibitor to sirolimus (SRL), a mechanistic target of rapamycin inhibitor (mTOR‐I), has been shown to enhance immunoregulatory profiles in liver transplant (LT) recipients (LTRs), mTOR‐I therapy might allow for increased success of immunosuppression (IS) withdrawal. Our aim was to determine if operational tolerance could be observed in LTRs withdrawn from SRL and if blood/graft tolerance biomarkers were predictive of successful withdrawal.

APPROACH AND RESULTS

We performed a prospective trial of SRL monotherapy withdrawal in nonimmune, nonviremic LTRs > 3 years post‐LT. SRL was weaned over ~6 months, and biopsies were performed 12 months postweaning or at concern for acute rejection. Twenty‐one LTRs consented; 6 were excluded due to subclinical acute rejection on baseline biopsy or other reasons, and 15 underwent weaning (age 61.3 ± 8.8 years; LT to SRL weaning 6.7 ± 3 years). Eight (53%) achieved operational tolerance (TOL). Of the 7 who were nontolerant (non‐TOL), 6 had mild acute rejection on biopsy near the end of weaning or at study end; 1 was removed from the trial due to liver cancer recurrence. At baseline preweaning, there were statistically increased blood tolerogenic dendritic cells and cell phenotypes correlating with chronic antigen presentation in the TOL versus non‐TOL groups. A previously identified biopsy gene signature accurately predicted TOL versus non‐TOL in 12/14 LTRs before weaning. At study end, biopsy staining revealed statistically significant increases in antigen‐presenting cell:leukocyte pairings, FOXP3+/CD4+ T cells, Tbet+/CD8+ T cells, and lobular dendritic cells in the non‐TOL group.

CONCLUSIONS

This study evaluated IS withdrawal directly from mTOR‐I therapy in LTRs and achieved > 50% operational tolerance. Preweaning gene expression and peripheral blood mononuclear cell profiling may be useful as predictors of successful mTOR‐I therapy withdrawal. NCT02062944.
Parental executive function as a predictor of parenting practices and children's executive function
Authors: Korucu Irem , Litkowski Ellen , Purpura David J. , Schmitt Sara A.
Published: November 2019

The family context has been identified as an important predictor of the development of children's executive function (EF). An emerging line of research demonstrates that parents' own EF is linked to their caregiving behaviours and their children's EF. However, researchers have yet to explore the extent to which parental EF is related to specific caregiving practices in the home that may be supportive of children's EF. In this study, we examined the extent to which parental EF is associated with children's EF and explored the role of general parenting practices as well as EF‐specific parenting activities in this relation using a sample of 197 preschoolers (50.3% male and 84.3% Caucasian) and their parents in the United States. Multivariate regressions indicated that parental EF was related to children's EF above and beyond general parenting and EF‐specific practices (β = .22, p = .003, CI [0.07, 0.36]). Additionally, a significant indirect relation emerged between parental EF and children's EF through EF‐specific activities (β = .04, CI [0.01, 0.10]). The potential importance of the family context for EF development and study implications are discussed.

Highlights

The purpose was to examine the associations among parent's EF, children's EF, and general parenting and EF‐ specific practices.

Parent's engagement in EF‐specific activities mediated the relation between parental EF and children's EF

Parent's own EF skills as well their engagement in EF‐specific activities may promote the development of children's EF.
Assessment of the expression of the immune checkpoint molecules PD‐1, CTLA4, TIM‐3 and LAG‐3 across different cancers in relation to treatment response, tumor‐infiltrating immune cells and survival
Authors: Tu Lei , Guan Renguo , Yang Hanting , Zhou Yu , Hong Weifeng , Ma Liheng , Zhao Guangzhe , Yu Min
Published: November 2019

Immune checkpoint molecules have been identified as crucial regulators of the immune response, which motivated the emergence of immune checkpoint‐targeting therapeutic strategies. However, the prognostic significance of the immune checkpoint molecules PD‐1, CTLA4, TIM‐3 and LAG‐3 remains controversial. The aim of our study was to conduct a systematic assessment of the expression of these immune checkpoint molecules across different cancers in relation to treatment response, tumor‐infiltrating immune cells and survival. Oncomine and PrognoScan database analyses were used to investigate the expression levels and prognostic values of these immune checkpoint molecule genes across various cancers. Then, we used Kaplan–Meier plotter to validate the associations between the checkpoint molecules and cancer survival identified in the PrognoScan analysis. TIMER analysis was used to evaluate immune cell infiltration data from The Cancer Genome Atlas. Finally, we used Gene Expression Profiling Interactive Analysis to investigate the prognostic value of these four checkpoint molecules and assess the correlations between these four checkpoint molecules and genetic markers. These immune checkpoint molecules may potentially serve as prognostic factors and therapeutic targets in breast cancer, ovarian cancer and lung cancer. The prognostic roles of these checkpoint molecules varied greatly across cancers, which implied a noteworthy amount of heterogeneity among tumors, even within the same molecular subtype. In addition, the expression patterns of these checkpoint molecules were closely associated with treatment response and provided some useful direction when choosing chemotherapeutic drugs. These findings enhance our understanding of these checkpoints in cancer treatment and identify strategies to promote synergistic activities in the context of other immunotherapies.
Association between initiation of adjuvant chemotherapy beyond 30 days after surgery and overall survival among patients with triple‐negative breast cancer
Authors: Heeg Erik , Marang‐van de Mheen Perla J. , Van Maaren Marissa C. , Schreuder Kay , Tollenaar Rob A.E.M. , Siesling Sabine , Bos Monique E.M.M. , Vrancken Peeters Marie‐Jeanne T.F.D.
Published: November 2019

Delayed time to chemotherapy (TTC) is associated with decreased outcomes of breast cancer patients. Recently, studies suggested that the association might be subtype‐dependent and that TTC within 30 days should be warranted in patients with triple‐negative breast cancer (TNBC). The aim of the current study is to determine if TTC beyond 30 days is associated with reduced 10‐year overall survival in TNBC patients. We identified all TNBC patients diagnosed between 2006 and 2014 who received adjuvant chemotherapy in the Netherlands. We distinguished between breast‐conserving surgery (BCS) vs. mastectomy given the difference in preoperative characteristics and outcomes. The association was estimated with hazard ratios (HRs) using propensity‐score matched Cox proportional hazard analyses. In total, 3,016 patients were included. In matched patients who underwent BCS (n = 904), 10‐year overall survival was favorable for patients with TTC within 30 days (84.4% vs. 76.9%, p = 0.001). Patients with TTC beyond 30 days were more likely than those with TTC within 30 days to die within 10 years after surgery (HR 1.69 (95% CI 1.22–2.34), p = 0.002). In matched patients who underwent mastectomy (n = 1,568), there was no difference in 10 years overall survival between those with TTC within or beyond 30 days (74.5% vs. 74.7%, p = 0.716), nor an increased risk of death for those with TTC beyond 30 days (HR 1.04 (95% CI 0.84–1.28), p = 0.716). Initiation of adjuvant chemotherapy beyond 30 days is associated with decreased 10 years overall survival in TNBC patients who underwent BCS. Therefore, timelier initiation of chemotherapy in TNBC patients undergoing BCS seems warranted.
Overcoming Challenges on an International Project to Advance Systems Engineering
Authors: Davidz Heidi , Ferris T.L.J. , Henry Devanandham , Hilburn Thomas B. , Hutchison Nicole A.C. , Olwell David H. , Prun Daniel , Pyster Art , Roussel Jean‐Claude , Sillitto Hillary , Snoderly John , Squires Alice F. , Zemrowski Ken
Published: November 2019

The Body of Knowledge and Curriculum to Advance Systems Engineering (BKCASE) project's dual product development cycle spanned a three‐year period from the September 2009 to December, 2012. During this timeframe, BKCASE authors met quarterly at various locations, primarily in various regions of the United States, but also in Stockholm, Sweden; Toulouse, France; London, England; and Rome, Italy (BKCASE, 2009–2019). The team successfully worked through challenges and differences to produce The Guide to the Systems Engineering Body of Knowledge (SEBoK) wiki and a Graduate Reference Curriculum for Systems Engineering (GRCSE) publication. This article is a collection of personal stories from the team members that focus on overcoming obstacles to successfully produce the final published products.
Globalizing the Certification of Systems Engineers
Authors: Wright Courtney
Published: November 2019

What defines an international airport? Flights to and from other countries? Big runways and high volume of passengers? US definitions of international airports focus on the facility's ability to process passengers entering from another country. They do not look at whether aircraft can or do enter that port, just whether their passengers are allowed to leave the airport if it is their first port of entry in the US. It is about what can, theoretically, be done with people from other countries, rather than how well people around the globe are actually interacting.

How do we define an international professional society or its international certification program? We might start by looking at the three factors listed above: May people from more than one country participate? Can people from more than one country participate? And, do people from more than one country participate? This “more than one country” bar is pretty easy to meet, thanks to the UK, so let's move to all countries. This is a much greater challenge and the logic behind referring to INCOSE as a global certification program rather than the easier international. In our context, international means including some other countries, often those with similar cultures or technologies, where global is both broader and deeper, and for us, this includes modifying our baseline certification practices in response to feedback from other cultures.
Optimal designs for pairwise calculation: An application to free energy perturbation in minimizing prediction variability
Authors: Yang Qingyi , Burchett Woodrow , Steeno Gregory S. , Liu Shuai , Yang Mingjun , Mobley David L. , Hou Xinjun
Published: November 2019

Pairwise‐based methods such as the free energy perturbation (FEP) method have been widely deployed to compute the binding free energy differences between two similar host–guest complexes. The calculated pairwise free energy difference is either directly adopted or transformed to absolute binding free energy for molecule rank ordering. We investigated, through both analytic derivations and simulations, how the selection of pairs in the experiment could impact the overall prediction precision. Our studies showed that (1) the estimated absolute binding free energy () derived from calculated pairwise differences (ΔΔG) through weighted least squares fitting is more precise in prediction than the pairwise difference values when the number of pairs is more than the number of ligands and (2) prediction precision is influenced by both the total number of pairs and the specifically selected pairs, the latter being critically important when the number of calculated pairs is limited. Furthermore, we applied optimal experimental design in pair selection and found that the optimally selected pairs can outperform randomly selected pairs in prediction precision. In an illustrative example, we showed that, upon weighing ligand structure similarity into design optimization, the weighted optimal designs are more efficient than the literature reported designs. This work provides a new approach to assess retrospective pairwise‐based prediction results, and a method to design new prospective pairwise‐based experiments for molecular lead optimization. © 2019 Wiley Periodicals, Inc.
Derangements of amino acids in cachectic skeletal muscle are caused by mitochondrial dysfunction
Authors: Kunzke Thomas , Buck Achim , Prade Verena M. , Feuchtinger Annette , Prokopchuk Olga , Martignoni Marc E. , Heisz Simone , Hauner Hans , Janssen Klaus‐Peter , Walch Axel , Aichler Michaela
Published: November 2019

Background

Cachexia is the direct cause of at least 20% of cancer‐associated deaths. Muscle wasting in skeletal muscle results in weakness, immobility, and death secondary to impaired respiratory muscle function. Muscle proteins are massively degraded in cachexia; nevertheless, the molecular mechanisms related to this process are poorly understood. Previous studies have reported conflicting results regarding the amino acid abundances in cachectic skeletal muscle tissues. There is a clear need to identify the molecular processes of muscle metabolism in the context of cachexia, especially how different types of molecules are involved in the muscle wasting process.

Methods

New in situ ‐omics techniques were used to produce a more comprehensive picture of amino acid metabolism in cachectic muscles by determining the quantities of amino acids, proteins, and cellular metabolites. Using matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry imaging, we determined the in situ concentrations of amino acids and proteins, as well as energy and other cellular metabolites, in skeletal muscle tissues from genetic mouse cancer models (n = 21) and from patients with cancer (n = 6). Combined results from three individual MALDI mass spectrometry imaging methods were obtained and interpreted. Immunohistochemistry staining for mitochondrial proteins and myosin heavy chain expression, digital image analysis, and transmission electron microscopy complemented the MALDI mass spectrometry imaging results.

Results

Metabolic derangements in cachectic mouse muscle tissues were detected, with significantly increased quantities of lysine, arginine, proline, and tyrosine (P = 0.0037, P = 0.0048, P = 0.0430, and P = 0.0357, respectively) and significantly reduced quantities of glutamate and aspartate (P = 0.0008 and P = 0.0124). Human skeletal muscle tissues revealed similar tendencies. A majority of altered amino acids were released by the breakdown of proteins involved in oxidative phosphorylation. Decreased energy charge was observed in cachectic muscle tissues (P = 0.0101), which was related to the breakdown of specific proteins. Additionally, expression of the cationic amino acid transporter CAT1 was significantly decreased in the mitochondria of cachectic mouse muscles (P = 0.0133); this decrease may play an important role in the alterations of cationic amino acid metabolism and decreased quantity of glutamate observed in cachexia.

Conclusions

Our results suggest that mitochondrial dysfunction has a substantial influence on amino acid metabolism in cachectic skeletal muscles, which appears to be triggered by diminished CAT1 expression, as well as the degradation of mitochondrial proteins. These findings provide new insights into the pathobiochemistry of muscle wasting.
Blockade of dopamine D1 receptors in male rats disrupts morphine reward in pain naïve but not in chronic pain states
Authors: Grenier Patrick , Mailhiot Madison C. , Cahill Catherine M. , Olmstead Mary C.
Published: November 2019

The rewarding effect of opiates is mediated through dissociable neural systems in drug naïve and drug‐dependent states. Neuroadaptations associated with chronic drug use are similar to those produced by chronic pain, suggesting that opiate reward could also involve distinct mechanisms in chronic pain and pain‐naïve states. We tested this hypothesis by examining the effect of dopamine (DA) antagonism on morphine reward in a rat model of neuropathic pain.Neuropathic pain was induced in male Sprague‐Dawley rats through chronic constriction (CCI) of the sciatic nerve; reward was assessed in the conditioned place preference (CPP) paradigm in separate groups at early (4‐8 days post‐surgery) and late (11‐15 days post‐surgery) phases of neuropathic pain. Minimal effective doses of morphine that produced a CPP in early and late phases of neuropathic pain were 6 mg/kg and 2 mg/kg respectively. The DA D1 receptor antagonist, SCH23390, blocked a morphine CPP in sham, but not CCI, rats at a higher dose (0.5 mg/kg), but had no effect at a lower dose (0.1 mg/kg). The DA D2 receptor antagonist, eticlopride (0.1 and 0.5 mg/kg), had no effect on a morphine CPP in sham or CCI rats, either in early or late phases of neuropathic pain. In the CPP paradigm, morphine reward involves DA D1 mechanisms in pain‐naïve but not chronic pain states. This could reflect increased sensitivity to drug effects in pain versus no pain conditions and/or differential mediation of opiate reward in these two states.