bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sweet orosensation induces Arc expression in dorsal hippocampal CA1 neurons in an Experience‐dependent manner
Authors: Henderson Yoko O. , Nalloor Rebecca , Vazdarjanova Almira , Parent Marise B. 
Published: September 2015

ABSTRACTThere is limited knowledge regarding how the brain controls the timing of meals. Similarly, there is a large gap in our understanding of how top‐down cognitive processes, such as memory influence energy intake. We hypothesize that dorsal hippocampal (dHC) neurons, which are critical for episodic memory, form a memory of a meal and inhibit meal onset during the postprandial period. In support, we showed previously that reversible inactivation of these neurons during the period following a sucrose meal accelerates the onset of the next meal. If dHC neurons form a memory of a meal, then consumption should induce synaptic plasticity in dHC neurons. To test this, we determined (1) whether a sucrose meal increases the expression of the synaptic plasticity marker activity‐regulated cytoskeleton‐associated protein (Arc) in dHC CA1 neurons, (2) whether previous experience with sucrose influences sucrose‐induced Arc expression, and (3) whether the orosensory stimulation produced by the noncaloric sweetener saccharin is sufficient to induce Arc expression. Male Sprague‐Dawley rats were trained to consume a sweetened solution at a scheduled time daily. On the experimental day, they were given a solution for 7 min, euthanized, and then fluorescence in situ hybridization procedures were used to measure meal‐induced Arc mRNA. Compared to caged control rats, Arc expression was significantly higher in rats that consumed sucrose or saccharin. Interestingly, rats given additional experience with sucrose had less Arc expression than rats with less sucrose experience, even though both groups consumed similar amounts on the experimental day. Thus, this study is the first to suggest that orosensory stimulation produced by consuming a sweetened solution and possibly the hedonic value of that sweet stimulation induces synaptic plasticity in dHC CA1 neurons in an experience‐dependent manner. Collectively, these findings are consistent with our hypothesis that dHC neurons form a memory of a meal. © 2015 Wiley Periodicals, Inc.
Rapid memory stabilization by transient theta coherence in the human medial temporal lobe
Authors: Thézé Raphaël , Guggisberg Adrian G. , Nahum Louis , Schnider Armin 
Published: September 2015

AbstractPresenting stimuli again after presentation of intervening stimuli improves their retention, an effect known as the spacing effect. However, using event‐related potentials (ERPs), we had observed that immediate, in comparison to spaced, repetition of pictures induced a positive frontal potential at 200–300 ms. This potential appeared to emanate from the left medial temporal lobe (MTL), a structure critical for memory consolidation. In this study, we tested the behavioral relevance of this signal and explored functional connectivity changes during picture repetition. We obtained high‐density electroencephalographic recordings from 14 healthy subjects performing a continuous recognition task where pictures were either repeated immediately or after 9 intervening items. Conventional ERP analysis replicated the positive frontal potential emanating from the left MTL at 250–350 ms in response to immediately repeated stimuli. Connectivity analysis showed that this ERP was associated with increased coherence in the MTL region—left more that right—in the theta‐band (3.5–7 Hz) 200–400 ms following immediate, but not spaced, repetition. This increase was stronger in subjects who better recognized immediately repeated stimuli after 30 min. These findings indicate that transient theta‐band synchronization between the MTL and the rest of the brain at 200–400 ms reflects a memory stabilizing signal. © 2015 Wiley Periodicals, Inc.
Effect of collagen‐glycosaminoglycan scaffold pore size on matrix mineralization and cellular behavior in different cell types
Authors: Murphy Ciara M. , Duffy Garry P. , Schindeler Aaron , O'brien Fergal J. 
Published: September 2015

AbstractWe have previously examined osteoblast behavior on porous collagen‐glycosaminoglycan (CG) scaffolds with a range of mean pore sizes demonstrating superior cell attachment and migration in scaffolds with the largest pores (325 μm). Scaffolds provide a framework for construct development; therefore, it is crucial to identify the optimal pore size for augmented tissue formation. Utilizing the same range of scaffolds (85 μm – 325 μm), this study aimed to examine the effects of mean pore size on subsequent osteoblast differentiation and matrix mineralization, and to understand the mechanism by which pore size influences behavior of different cell types. Consequently, primary mesenchymal stem cells (MSCs) were assessed and their behavior compared to osteoblasts. Results demonstrated that scaffolds with the largest pore size (325 μm) facilitated improved osteoblast infiltration, earlier expression of mature bone markers osteopontin (OPN) and osteocalcin (OCN), and increased mineralization. MSCs responded similarly to osteoblasts whereby cell attachment and scaffold infiltration improved with increasing pore size. However, MSCs showed reduced cell motility, proliferation, and scaffold infiltration compared to osteoblasts. This was associated with differences in the profile of integrin subunits (α2) and collagen receptors (CD44), indicating that osteoblasts have a stronger affinity for CG scaffolds compared to MSCs. In summary, these results reveal how larger pores promote improved cell infiltration, essential for construct development, however the optimal scaffold pore size can be cell type specific. As such, this study highlights a necessity to tailor both scaffold micro‐architecture and cell‐type when designing constructs for successful bone tissue engineering applications. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 291–304, 2016.
Preparation and characterization of directed, one‐day‐self‐assembled millimeter‐size spheroids of adipose‐derived mesenchymal stem cells
Authors: Iwai Ryosuke , Nemoto Yasushi , Nakayama Yasuhide 
Published: September 2015

AbstractThree‐dimensional cell spheroids prepared without using any artificial scaffold materials are desirable for cell‐based transplants. However, conventional cell culture systems are inefficient for rapid, large‐scale and non‐cytotoxic generation of size‐controlled spheroids (>1 mm diameter) that are required for tissue regenerative therapy application. In this study, we prepared millimeter‐order spheroids of adipose‐derived mesenchymal stem cells (ADSCs) by controlling the spheroid size (diameter range: 0.4–2.5 mm). Notably, spheroid generation required only one day of culture on charged culture dishes. Almost all spheroid‐derived ADSCs were viable and produced adhesion molecules and growth factors, which play an important role in tissue regeneration. Moreover, spheroid‐derived ADSCs could infiltrate and recellularize collagenous tissue membranes in vitro. The ADSC spheroids developed in this study could be directly (without additional processing) used for cell‐based tissue regeneration therapy. Furthermore, the rapid scale‐up process and noncytotoxic generation of spheroids would also enable other applications such as use as screening models for drug discovery. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 305–312, 2016.
Identification of optimal site of G1 placement for median orthodromic palmar nerve conduction study
Authors: Devine Irisa M. , Rubin Devon I. 
Published: September 2015

ABSTRACTIntroduction: G1 electrode placement at the distal wrist crease during the median orthodromic palmar nerve conduction study (NCS) could result in a false negative study if compression is more proximal. Methods: In this study we aimed to determine the effect of median G1 electrode placement on distal latencies and amplitudes. Methods Median orthodromic palmar NCS was performed with the G1 electrode at the wrist crease and 2 cm proximal, stimulating 8 cm distal to G1. The difference in the distal latencies and amplitudes between the 2 recording sites was calculated. Results: In 26 controls and 25 carpal tunnel syndrome (CTS) patients, the mean proximal–distal latency difference and percent amplitude decrease (distal vs. proximal) was −0.085 ms/53% (controls) and −0.072 ms/45% (CTS). Conclusion: Distal latency is not significantly affected by G1 placement in the median orthodromic palmar NCS, but the amplitudes are nearly twice as high when G1 is placed 2 cm proximal to the wrist crease. Muscle Nerve 53: 579–582, 2016
A phase‐field model for chemo‐mechanical induced fracture in lithium‐ion battery electrode particles
Authors: Miehe C. , Dal H. , Schänzel L.‐M. , Raina A. 
Published: September 2015

SummaryCapacity fade in conventional Li‐ion battery systems due to chemo‐mechanical degradation during charge–discharge cycles is the bottleneck in high‐performance battery design. Stresses generated by diffusion‐mechanical coupling in Li‐ion intercalation and deintercalation cycles, accompanied by swelling and shrinking at finite strains, cause micro‐cracks, which finally disturb the electrical conductivity and isolate the electrode particles. This leads to battery capacity fade. As a first attempt towards a reliable description of this complex phenomenon, we propose a novel finite strain theory for chemo‐elasticity coupled with phase‐field modeling of fracture, which regularizes a sharp crack topology. We apply a rigorous geometric approach to the diffusive crack modeling based on the introduction of a global evolution equation of regularized crack surface, governed by the crack phase field. The irreversible evolution of the crack phase field is modeled through a novel critical stress‐based growth function. A modular concept is outlined for linking of the diffusive crack modeling to the complex chemo‐elastic material response of the bulk material. Here, we incorporate standard as well as gradient‐extended Cahn–Hilliard‐type diffusion for the Li‐ions, where the latter accounts for a possible phase segregation. From the viewpoint of the methodology, the separation of modules for the crack evolution and the bulk response provides a highly attractive and transparent structure of the multi‐physics problem. This structure is exploited on the numerical side by constructing a robust finite element method, based on an algorithmic decoupling of updates for the crack phase field and the state variables of the chemo‐mechanical bulk response. We demonstrate the performance of the proposed coupled multi‐field formulation by an analysis of representative boundary value problems. Copyright © 2015 John Wiley & Sons, Ltd.
Number needed to harm in the post‐marketing safety evaluation: results for rosiglitazone and pioglitazone
Authors: Mendes Diogo , Alves Carlos , Batel‐Marques Francisco 
Published: September 2015

AbstractPurposeOur aim is to investigate the usefulness of metric indices in post‐marketing safety evaluations by estimating number needed to harm (NNH) values for cardiovascular (CV) adverse outcomes for rosiglitazone and pioglitazone.MethodsReports from regulatory authorities (RAs) were consulted, and Medline searches were performed to identify studies assessing CV risks [all‐cause death, CV death, myocardial infarction (MI), stroke, or congestive heart failure (CHF)] for thiazolidinediones. Meta‐analyses were performed to pool evidence from randomized controlled trials (RCTs) and observational studies (OS). NNHs [with 95% confidence intervals (CI)] per year were estimated for CV adverse events.ResultsReports from RAs included two meta‐analyses of short‐term RCTs, two long‐term RCTs (RECORD and PROACTIVE), and a systematic review of OS (n = 29). The Medline search identified six additional OS. Statistically significant NNH values were obtained for the following: (i) rosiglitazone versus control on MI and CHF in the meta‐analysis of RCTs (NNH = 16; 95%CI = 10–255; and NNH = 7; 95%CI = 5–16, respectively) and meta‐analysis of OS (NNH = 12; 95%CI = 9–20; and NNH = 5; 95%CI = 32–131, respectively) and on CHF in the RECORD (NNH = 6; 95%CI = 4–14); (ii) pioglitazone versus control on CHF (NNH = 11; 95%CI = 6, 403) in the meta‐analysis of RCTs and PROACTIVE (NNH = 12; 95%CI = 8–43); and (iii) rosiglitazone versus pioglitazone on MI (NNH = 69; 95%CI = 32–379), stroke (NNH = 36; 95%CI = 20–225), CHF (NNH = 33; 95%CI = 19–47), and all‐cause death (NNH = 63; 95%CI = 49–100) in the meta‐analysis of OS.ConclusionThe NNH values suggested an increased CV risk with rosiglitazone versus pioglitazone across several sources of information. The inclusion of objective metrics in post‐marketing drug's benefit–risk assessments could be of increased value and help RAs to make consistent decisions on drug safety. Copyright © 2015 John Wiley & Sons, Ltd.
Pressure‐induced structural transition of mature HIV‐1 protease from a combined NMR/MD simulation approach
Authors: Roche Julien , Louis John M. , Bax Ad , Best Robert B. 
Published: September 2015

ABSTRACTWe investigate the pressure‐induced structural changes in the mature human immunodeficiency virus type 1 protease dimer, using residual dipolar coupling (RDC) measurements in a weakly oriented solution. 1DNH RDCs were measured under high‐pressure conditions for an inhibitor‐free PR and an inhibitor‐bound complex, as well as for an inhibitor‐free multidrug resistant protease bearing 20 mutations (PR20). While PR20 and the inhibitor‐bound PR were little affected by pressure, inhibitor‐free PR showed significant differences in the RDCs measured at 600 bar compared with 1 bar. The structural basis of such changes was investigated by MD simulations using the experimental RDC restraints, revealing substantial conformational perturbations, specifically a partial opening of the flaps and the penetration of water molecules into the hydrophobic core of the subunits at high pressure. This study highlights the exquisite sensitivity of RDCs to pressure‐induced conformational changes and illustrates how RDCs combined with MD simulations can be used to determine the structural properties of metastable intermediate states on the folding energy landscape. Proteins 2015; 83:2117–2123. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
p53‐Based strategy to reduce hematological toxicity of chemotherapy: A proof of principle study
Authors: Ha Chul S. , Michalek Joel E. , Elledge Richard , Kelly Kevin R. , Ganapathy Suthakar , Su Hang , Jenkins Carol A. , Argiris Athanassios , Swords Ronan , Eng Tony Y. , Karnad Anand , Crownover Richard L. , Swanson Gregory P. , Goros Martin , Pollock Brad H. , Yuan Zhi-Min 
Published: September 2015

p53 activation is a primary mechanism underlying pathological responses to DNA damaging agents such as chemotherapy and radiotherapy. Our recent animal studies showed that low dose arsenic (LDA)‐induced transient p53 inhibition selectively protected normal tissues from chemotherapy‐induced toxicity.Study objectives were to: 1) define the lowest safe dose of arsenic trioxide that transiently blocks p53 activation in patients and 2) assess the potential of LDA to decrease hematological toxicity from chemotherapy.Patients scheduled to receive minimum 4 cycles of myelosuppressive chemotherapy were eligible. For objective 1, dose escalation of LDA started at 0.005 mg/kg/day for 3 days. This dose satisfied objective 1 and was administered before chemotherapy cycles 2, 4, and 6 for objective 2. p53 level in peripheral lymphocytes was measured on day 1 of each cycle by ELISA assay. Chemotherapy cycles 1, 3, and 5 served as the baseline for the subsequent cycles of 2, 4, and 6 respectively. If p53 level for the subsequent cycle was lower (or higher) than the baseline cycle, p53 was defined as “suppressed” (or “activated”) for the pair of cycles. Repeated measures linear models of CBC in terms of day, cycle, p53 activity and interaction terms were used.Twenty‐six patients treated with 3 week cycle regimens form the base of analyses. The mean white blood cell, hemoglobin and absolute neutrophil counts were significantly higher in the “suppressed” relative to the “activated” group.These data support the proof of principle that suppression of p53 could lead to protection of bone marrow in patients receiving chemotherapy.This trial is registered in ClinicalTrials.gov. Identifier: NCT01428128.
Executive summary of the CAEP 2014 Academic Symposium: How to make research succeed in your department
Authors: Stiell Ian G. , Artz Jennifer D. , Perry Jeffrey , Vaillancourt Christian , Calder Lisa 
Published: September 2015

AbstractThe vision of the recently created Canadian Association of Emergency Physicians (CAEP) Academic Section is to promote high-quality emergency patient care by conducting world-leading education and research in emergency medicine. The Academic Section plans to achieve this goal by enhancing academic emergency medicine primarily at Canadian medical schools and teaching hospitals. It seeks to foster and develop education, research, and academic leadership amongst Canadian emergency physicians, residents, and students. In this light, the Academic Section began in 2013 to hold the annual Academic Symposia to highlight best practices and recommendations for the three core domains of governance and leadership, education scholarship, and research. Each year, members of three panels are asked to review the literature, survey and interview experts, achieve consensus, and present their recommendations at the Symposium (2013, Education Scholarship; 2014, Research; and 2015, Governance and Funding).Research is essential to medical advancement. As a relatively young specialty, emergency medicine is rapidly evolving to adapt to new diagnostic tools, the challenges of crowding in emergency departments, and the growing needs of emergency patients. There is significant variability in the infrastructure, support, and productivity of emergency medicine research programs across Canada. All Canadians benefit from an investigation of the means to improve research infrastructure, training programs, and funding opportunities. Such an analysis is essential to identify areas for improvement, which will support the expansion of emergency medicine research. To this end, physician-scientist leaders were gathered from across Canada to develop pragmatic recommendations on the improvement of emergency medicine research through a comprehensive analysis of current best practices, systematic literature reviews, stakeholder surveys, and expert interviews.
Lactase non-persistence as a determinant of milk avoidance and calcium intake in children and adolescents
Authors: Almon Ricardo , Sjöström Michael , Nilsson Torbjörn K. 
Published: September 2015

AbstractThis study examines if lactase non-persistent (LNP) children and adolescents differ from those who are lactase persistent (LP) as regards milk avoidance and Ca intake. We also studied potential differences in anthropometric features related to obesity, and examined if milk avoidance is associated with lactase-persistence status. Additionally, we aimed to determine if heterozygous subjects showed an intermediary phenotype as regards Ca intake. Furthermore, we tested if LP and LNP influence vitamin D intake. The European Youth Heart Study is an ongoing international, multi-centre cohort study primarily designed to address CVD risk factors. Children (n298, mean age 9·6 years) and adolescents (n386, mean age 15·6 years) belonging to the Swedish part of the European Youth Heart Study were genotyped for the LCT-13910 C > T polymorphism. Mendelian randomisation was used. Milk avoidance was significantly more common in LNP adolescents (OR 3·2; 95% CI 1·5, 7·3). LP subjects had higher milk consumption (P < 0·001). Accordingly, energy consumption derived from milk and Ca intake was lower in LNP (P < 0·05 andP < 0·001, respectively). Heterozygous subjects did not show an intermediary phenotype concerning milk consumption. LP or LNP status did not affect vitamin D intake or anthropometric variables. LNP in children and adolescents is associated with reduced intake of milk and some milk-product-related nutritional components, in particular Ca. This reduced intake did not affect the studied anthropometric variables, indicators of body fat or estimated vitamin D intake. However, independently of genotype, age and sex, daily vitamin D intake was below the recommended intakes. Milk avoidance among adolescents but not children was associated with LNP.
Critical care for paediatric patients with heart failure
Authors: Costello John M. , Mazwi Mjaye L. , McBride Mary E. , Gambetta Katherine E. , Eltayeb Osama , Epting Conrad L. 
Published: September 2015

AbstractThis review offers a critical-care perspective on the pathophysiology, monitoring, and management of acute heart failure syndromes in children. An in-depth understanding of the cardiovascular physiological disturbances in this population of patients is essential to correctly interpret clinical signs, symptoms and monitoring data, and to implement appropriate therapies. In this regard, the myocardial force–velocity relationship, the Frank–Starling mechanism, and pressure–volume loops are discussed. A variety of monitoring modalities are used to provide insight into the haemodynamic state, clinical trajectory, and response to treatment. Critical-care treatment of acute heart failure is based on the fundamental principles of optimising the delivery of oxygen and minimising metabolic demands. The former may be achieved by optimising systemic arterial oxygen content and the variables that determine cardiac output: heart rate and rhythm, preload, afterload, and contractility. Metabolic demands may be decreased by a number of ways including positive pressure ventilation, temperature control, and sedation. Mechanical circulatory support should be considered for refractory cases. In the near future, monitoring modalities may be improved by the capture and analysis of complex clinical data such as pressure waveforms and heart rate variability. Using predictive modelling and streaming analytics, these data may then be used to develop automated, real-time clinical decision support tools. Given the barriers to conducting multi-centre trials in this population of patients, the thoughtful analysis of data from multi-centre clinical registries and administrative databases will also likely have an impact on clinical practice.
Echocardiographic evaluation of the failing heart
Authors: Parthiban Anitha , Shirali Girish 
Published: September 2015

AbstractHeart failure in children can result from a wide range of aetiologies and can manifest in systolic and/or diastolic dysfunction. Echocardiography is the primary test for the diagnosis and follow-up of children with heart failure. In this article, we critically review standard echocardiographic measurements that have been shown to have prognostic importance in children with various types of heart failure. Each of the common forms of cardiomyopathy that is encountered in childhood – dilated, hypertrophic, restrictive, left ventricular non-compaction, and arrhythmogenic right ventricular cardiomyopathy – is discussed separately. Special attention is paid to the failing right ventricle, both in the systemic and in the sub-pulmonary position, to the failing univentricular heart, and to the assessment of diastolic function in children.