bluuebunny/crossref_metadata_2025_split huggingface dataset:
Musculoskeletal structure and function in response to the combined effect of an obesogenic diet and age in male C57BL/6J mice
Authors: Bott Kirsten N. , Gittings William , Fajardo Val Andrew , Baranowski Bradley J. , Vandenboom Rene , LeBlanc Paul J. , Ward Wendy E. , Peters Sandra J. 
Published: May 2017

ScopeThe effects of a long‐term high fat and sucrose diet (HFS) superimposed with aging on bone and muscle structure and/or function.Methods and resultsMale C57BL/6J mice (20 weeks of age) were randomized to 1 of 3 groups: baseline (BSL, n = 12), or assigned to a control (AGE, n = 12) or HFS (HFS‐AGE, n = 11) diet for 13 weeks. Trabecular bone structure, volumetric bone mineral density (vBMD), and body composition, were measured longitudinally at 20, 24, and 32 weeks of age. In vitro contractile measures were performed on isolated soleus and extensor digitorum longus (EDL) muscles for each group. Both AGE and HFS‐AGE had similar declines in trabecular bone structure, while HFS‐AGE resulted in increased soleus cross‐sectional area (CSA) compared to AGE, but this did not translate to greater twitch or tetanic peak force. The ratio of outcomes of bone to muscle declined in both AGE and HFS‐AGE compared to BSL as a result of greater declines in trabecular bone structure than muscle function.ConclusionConsumption of a 13‐week HFS diet at 20 weeks of age did not exacerbate age‐related declines in bone or muscle, but these tissues do not decline in a coordinate manner with greater declines in bone than muscle.
Incidence of nonamyloidogenic mutations in the transthyretin gene in patients with autonomic and small fiber neuropathy
Authors: Levine Todd D. , Bland Ruth J. 
Published: May 2017

ABSTRACTIntroduction: Mutations of the transthyretin (TTR) gene have been associated with polyneuropathy; the protein product has a tendency to form amyloid deposits in the peripheral nervous system. Methods: Patients with small fiber neuropathy (SFN) with or without autonomic symptoms were given skin biopsies to assess nerve fiber density. Any patient with autonomic symptoms was assessed for autonomic neuropathy (AN). If testing revealed no clear cause of neuropathy, the TTR gene was sequenced. Results: Thirty‐six percent of patients were found to harbor at least 1 mutation in the TTR gene sequence (variants of unknown significance [VUS]). Of 24 patients diagnosed with SFN, 8% of patients had a point mutation (c76G>A). Of those patients who were diagnosed with both SFN and AN, 68% of patients had a VUS within the TTR gene (c76G>A, c337‐18G>C). Conclusions: The results suggest an association between presumed nonamyloidogenic mutations in the TTR gene and the development of AN and SFN. Muscle Nerve 57: 140–142, 2017
Acute nutritional axonal neuropathy
Authors: Hamel Johanna , Logigian Eric L. 
Published: May 2017

ABSTRACTIntroduction: This study describes clinical, laboratory, and electrodiagnostic features of a severe acute axonal polyneuropathy common to patients with acute nutritional deficiency in the setting of alcoholism, bariatric surgery (BS), or anorexia. Methods: Retrospective analysis of clinical, electrodiagnostic, and laboratory data of patients with acute axonal neuropathy. Results: Thirteen patients were identified with a severe, painful, sensory or sensorimotor axonal polyneuropathy that developed over 2–12 weeks with sensory ataxia, areflexia, variable muscle weakness, poor nutritional status, and weight loss, often with prolonged vomiting and normal cerebrospinal fluid protein. Vitamin B6 was low in half and thiamine was low in all patients when obtained before supplementation. Patients improved with weight gain and vitamin supplementation, with motor greater than sensory recovery. Discussion: We suggest that acute or subacute axonal neuropathy in patients with weight loss or vomiting associated with alcohol abuse, BS, or dietary deficiency is one syndrome, caused by micronutrient deficiencies. Muscle Nerve 57: 33–39, 2018
Motor milestone assessment of infants with spinal muscular atrophy using the hammersmith infant neurological Exam—Part 2: Experience from a nusinersen clinical study
Authors: Bishop Kathie M. , Montes Jacqueline , Finkel Richard S. 
Published: May 2017

ABSTRACTIntroduction:In this study we examined the feasibility of assessing motor milestone performance of infants with spinal muscular atrophy (SMA) using the Hammersmith Infant Neurological Exam—Part 2 (HINE‐2) in a phase 2 study of nusinersen.Methods:Nineteen SMA infants were assessed using the HINE‐2 at baseline (≤7 months of age), and periodically up to 39 months of age. We evaluated whether the HINE‐2 was feasible, reliable, and sensitive to change.Results:Motor milestone assessments in SMA infants were feasible using the HINE‐2. Baseline test–retest reliability was excellent (R= 0.987;P< 0.0001). SMA infants were extremely low functioning at baseline and the HINE‐2 was able to detect changes over time in 16 of 19 infants within all 8 domains. HINE‐2 improvements were correlated with changes in other neuromuscular outcome measures.Conclusion:Results support the use of the HINE‐2 motor milestone assessment in clinical trials of SMA infants.Muscle Nerve57: 143–146, 2017
Ultrasonography in neuralgic amyotrophy: Sensitivity, spectrum of findings, and clinical correlations
Authors: ArÁnyi Zsuzsanna , Csillik Anita , DéVay Katalin , Rosero Maja , Barsi PéTer , BÖhm Josef , Schelle Thomas 
Published: May 2017

ABSTRACTIntroductionThe aim of this study was to assess the value of ultrasonography in neuralgic amyotrophy.MethodsFifty‐three patients with 70 affected nerves were examined with high‐resolution ultrasound.ResultsThe most commonly affected nerve was the anterior interosseous (23%). Ultrasonographic abnormalities in the affected nerves, rather than in the brachial plexus, were observed, with an overall sensitivity of 74%. Findings included the swelling of the nerve/fascicle with or without incomplete/complete constriction and rotational phenomena (nerve torsion and fascicular entwinement). A significant difference was found among the categories of ultrasonographic findings with respect to clinical outcome (P = 0.01). In nerves with complete constriction and rotational phenomena, reinnervation was absent or negligible, indicating surgery was warranted.DiscussionUltrasonography may be used as a diagnostic aid in neuralgic amyotrophy, which was hitherto a clinical and electrophysiological diagnosis, and may also help in identifying potential surgical candidates. Muscle Nerve 56: 1054–1062, 2017
A new method for coarsening tetrahedral meshes
Authors: Liu Jianfei , Shang Feifei , Song Ting 
Published: May 2017

SummaryTo coarsen a mesh, we usually remove a set of selected nodes one by one. Currently, the basic operation used to remove a node is edge collapsing, which does not perform well when applied to handling narrow regions in a tetrahedron mesh and could produce low‐quality elements or even fail to give valid results. To overcome the drawbacks of edge collapsing, we present a new node‐removal operator created by revising a topological transformation called small polyhedron reconnection. This new operator can guarantee success if the cavity that forms after a node is removed is meshable, and it produces higher‐quality results and keeps the nodes unmoved, which is preferred for applications such as multigrid hierarchies.In addition, 2 other aspects of mesh coarsening that determine whether a node should be removed and the sequence in which to remove the selected nodes are also studied. Our strategy consists of constructing a coarse node set using the sphere‐packing method and removing the nodes in a reversed kd‐tree sequence. The excellent performance of the new method is demonstrated by applying it to examples of adaptive meshing and multigrid hierarchy creation and comparing the results with those of the edge collapsing method.
Comparative Effectiveness of Oral Antiplatelet Agents in Patients with Acute Coronary Syndrome
Authors: Kim Kibum , Lee Todd A. , Ardati Amer K. , DiDomenico Robert J. , Touchette Daniel R. , Walton Surrey M. 
Published: May 2017

ObjectiveIn randomized controlled trials, prasugrel and ticagrelor reduced cardiovascular complications in patients with acute coronary syndrome (ACS) compared with clopidogrel. However, limited head‐to‐head comparisons have been conducted across the three antiplatelet agents using real‐world data. The aim of this study was to compare clinical outcomes of three strategies during a 1‐year period after percutaneous coronary intervention (PCI).MethodsRates of all‐cause and acute myocardial infarction (AMI) hospitalizations were compared retrospectively using an insurance claims database. Patients who filled a prescription for an oral antiplatelet agent between September 2011 and December 2013 for post ACS‐PCI care were identified. Time to all‐cause and AMI hospitalization for a 365‐day postdischarge period was compared using Cox proportional hazard models controlling for potential confounders within a propensity score matched cohort.ResultsA matched cohort of 9504 clopidogrel, 7128 prasugrel, and 2376 ticagrelor patients was analyzed. The 1‐year hazard ratio (HR) for the two newer agents versus clopidogrel was 0.84 (0.78–0.91). The HR for the newer agents versus clopidogrel of admission with AMI as the primary diagnosis was 0.78 (0.61–1.03), and for AMI as any diagnosis during a hospitalization was 0.88 (0.77–1.00). The HR of all‐cause admission for ticagrelor versus prasugrel was 0.97 (0.84–1.13), and the HRs of AMI‐related admission were not statistically significant between the two agents. Robustness checks across statistical methods to control for potential confounders did not influence the conclusion.ConclusionThis real‐world study demonstrated that use of the newer agents following PCI was associated with a decrease in all‐cause and AMI‐related hospitalizations. However, no significant difference was found in the rate of admission between ticagrelor versus prasugrel. Due to concerns regarding statistical power, future studies should examine larger cohorts to obtain more precise estimates for AMI hospitalization for ticagrelor and prasugrel.
Lixisenatide, a Once‐Daily Prandial Glucagon‐Like Peptide‐1 Receptor Agonist for the Treatment of Adults with Type 2 Diabetes
Authors: Trujillo Jennifer M. , Goldman Jennifer 
Published: May 2017

Lixisenatide, a short‐acting glucagon‐like peptide‐1 receptor agonist (GLP‐1 RA), has been available in Europe since 2013 and was recently approved in the United States for the treatment of type 2 diabetes (T2D) as an adjunct to diet and exercise. The objective of this systematic review is to describe the pharmacology, pharmacokinetics, safety, and efficacy of lixisenatide in patients with T2D. We conducted a search of the EMBASE database, limited to human studies with abstracts available in English. Published conference abstracts, limited to the American Diabetes Association (ADA) and the European Association for the Study of Diabetes meetings in 2015, as well as abstracts presented at the ADA meeting in 2016, were also screened. The abstracts retrieved were assessed for relevance; review articles and meta‐analyses focusing on GLP‐1 RAs as a class were excluded. Lixisenatide induced mean reductions of 0.46–0.99% in glycated hemoglobin A1c (HbA1c), 55.86–143.43 mg/dl in 2‐hour postprandial glucose (PPG) levels, and 56.58–127.75 mg/dl in mealtime glucose level variations. Changes in fasting plasma glucose (FPG) levels and weight ranged from −21.98 to +5.41 mg/dl and from −2.96 to +0.3 kg, respectively, in patients with T2D enrolled in the GetGoal clinical program (a program of clinical trials that established the efficacy and safety profile of lixisenatide 20 μg once/day across patients with T2D with differing background therapies). Lixisenatide was well tolerated, demonstrating rates of symptomatic hypoglycemia of 0.8–42.9% and a very low rate of severe hypoglycemia (< 1.5%) as well as no increased risk of cardiovascular events. The most common adverse events were gastrointestinal in nature, mainly transient nausea and vomiting of mild‐to‐moderate severity. Lixisenatide effectively lowers HbA1c levels in patients with T2D through a mechanism of action complementary to that of agents that mainly target FPG, with the additional benefit of weight loss. Its once‐daily administration schedule and effect on PPG levels make it an attractive option as add‐on treatment to basal insulin therapy or oral antidiabetic agents.
Microproteomics with microfluidic‐based cell sorting: Application to 1000 and 100 immune cells
Authors: Kasuga Kie , Katoh Yasutake , Nagase Keisuke , Igarashi Kazuhiko 
Published: May 2017

Ultimately, cell biology seeks to define molecular mechanisms underlying cellular functions. However, heterogeneity within cell populations must be considered for optimal assay design and data interpretation. Although single‐cell analyses are desirable for addressing this issue, practical considerations, including assay sensitivity, limit their broad application. Therefore, omics studies on small numbers of cells in defined subpopulations represent a viable alternative for elucidating cell functions at the molecular level. MS‐based proteomics allows in‐depth proteome exploration, although analyses of small numbers of cells have not been pursued due to loss during the multistep procedure involved. Thus, optimization of the proteomics workflow to facilitate the analysis of rare cells would be useful. Here, we report a microproteomics workflow for limited numbers of immune cells using non‐damaging, microfluidic chip‐based cell sorting and MS‐based proteomics. Samples of 1000 or 100 THP‐1 cells were sorted, and after enzymatic digestion, peptide mixtures were subjected to nano‐LC‐MS analysis. We achieved reasonable proteome coverage from as few as 100‐sorted cells, and the data obtained from 1000‐sorted cells were as comprehensive as those obtained using 1 μg of whole cell lysate. With further refinement, our approach could be useful for studying cell subpopulations or limited samples, such as clinical specimens.
Translocation of cell‐penetrating peptides into Candida fungal pathogens
Authors: Gong Zifan , Karlsson Amy J. 
Published: May 2017

AbstractCell‐penetrating peptides (CPPs) are small peptides capable of crossing cellular membranes while carrying molecular cargo. Although they have been widely studied for their ability to translocate nucleic acids, small molecules, and proteins into mammalian cells, studies of their interaction with fungal cells are limited. In this work, we evaluated the translocation of eleven fluorescently labeled peptides into the important human fungal pathogens Candida albicans and C. glabrata and explored the mechanisms of translocation. Seven of these peptides (cecropin B, penetratin, pVEC, MAP, SynB, (KFF)3K, and MPG) exhibited substantial translocation (>80% of cells) into both species in a concentration‐dependent manner, and an additional peptide (TP‐10) exhibiting strong translocation into only C. glabrata. Vacuoles were involved in translocation and intracellular trafficking of the peptides in the fungal cells and, for some peptides, escape from the vacuoles and localization in the cytosol were correlated to toxicity toward the fungal cells. Endocytosis was involved in the translocation of cecropin B, MAP, SynB, MPG, (KFF)3K, and TP‐10, and cecropin B, penetratin, pVEC, and MAP caused membrane permeabilization during translocation. These results indicate the involvement of multiple translocation mechanisms for some CPPs. Although high levels of translocation were typically associated with toxicity of the peptides toward the fungal cells, SynB was translocated efficiently into Candida cells at concentrations that led to minimal toxicity. Our work highlights the potential of CPPs in delivering antifungal molecules and other bioactive cargo to Candida pathogens.
Effects of aligned α‐helix peptide dipoles on experimental electrostatic potentials
Authors: Wang Jimin , Videla Pablo E. , Batista Victor S. 
Published: May 2017

AbstractAligned protein α‐helix dipoles have been implicated in protein function and structure. The recent breakthroughs in high‐resolution electron microscopy (EM) of macromolecules makes it possible to explore fundamental aspects of structural biology at the detailed molecular level. The electrostatic potential (ESP) generated by aligned protein α‐helix dipole should be observable in high‐resolution EM maps despite the fact that the effect may be partially screened by induced electric fields. Here, we show that aligned backbone dipoles in protein α‐helices account for long‐range features in the protein ESP functions. Our results are consistent with experimental EM maps and density functional theory calculations, including direct Fourier summation for proper calculation of the ESP due to the nonlocal nature of the ESP function from aligned dipoles and other partial atomic charges.
Insecticidal activities of their components derived from the essential oils of Cinnamomum sp. barks and against Ricania sp. (Homoptera: Ricaniidae), a newly recorded pest
Authors: Jeon Ye‐Jin , Lee Sang‐Guei , Yang Young‐Cheol , Lee Hoi‐Seon 
Published: May 2017

AbstractBACKGROUNDInsecticidal activities of Cinnamomum cassia and Cinnamomum zeylanicum oils and their components are not known against Ricania sp. Insecticidal activities of major components derived from C. cassia and C. zeylanicum oils were examined in spray and leaf‐dipping bioassays against Ricania sp. nymphs and adults.RESULTSThe LC50 value of C. cassia and C. zeylanicum oils was 37.66 and 72.62 mg L–1, respectively, in leaf‐dipping bioassays against Ricania sp. nymphs, and 77.38 and 134.86 mg L–1 in spray bioassays against Ricania sp. adults. The insecticidal activity of C. cassia oil was 1.74–1.93 times greater than that of C. zeylanicum oil. When examined by gas chromatography mass spectrometry, the cinnamaldehyde content of C. cassia and C. zeylanicum oils was 80.20% and 46.32%, respectively. Based on the LC50 values of cinnamaldehyde, hydrocinnamaldehyde and 4‐hydroxy‐3‐methoxycinnamaldehyde against Ricania sp. nymphs and adults, cinnamaldehyde (LC50, 31.25 and 62.43 mg L–1) demonstrated the most potent insecticidal activity, followed by 4‐hydroxy‐3‐methoxycinnamaldehyde (172.19 and 212.77 mg L–1) and hydrocinnamaldehyde (275.05 and 318.63 mg L–1).CONCLUSIONThe findings revealed that C. cassia oil, C. zeylanicum oil and cinnamaldehyde have potential value in the management of Ricania sp. and could be valuable as effective insecticides. © 2017 Society of Chemical Industry
Evaluation of peroxidative stress of cancer cells in vitro by real‐time quantification of volatile aldehydes in culture headspace
Authors: Shestivska Violetta , Rutter Abigail V. , Sulé‐Suso Josep , Smith David , Španěl Patrik 
Published: May 2017

RationalePeroxidation of lipids in cellular membranes results in the release of volatile organic compounds (VOCs), including saturated aldehydes. The real‐time quantification of trace VOCs produced by cancer cells during peroxidative stress presents a new challenge to non‐invasive clinical diagnostics, which as described here, we have met with some success.MethodsA combination of selected ion flow tube mass spectrometry (SIFT‐MS), a technique that allows rapid, reliable quantification of VOCs in humid air and liquid headspace, and electrochemistry to generate reactive oxygen species (ROS) in vitro has been used. Thus, VOCs present in the headspace of CALU‐1 cancer cell line cultures exposed to ROS have been monitored and quantified in real time using SIFT‐MS.ResultsThe CALU‐1 lung cancer cells were cultured in 3D collagen to mimic in vivo tissue. Real‐time SIFT‐MS analyses focused on the volatile aldehydes: propanal, butanal, pentanal, hexanal, heptanal and malondialdehyde (propanedial), that are expected to be products of cellular membrane peroxidation. All six aldehydes were identified in the culture headspace, each reaching peak concentrations during the time of exposure to ROS and eventually reducing as the reactants were depleted in the culture. Pentanal and hexanal were the most abundant, reaching concentrations of a few hundred parts‐per‐billion by volume, ppbv, in the culture headspace.ConclusionsThe results of these experiments demonstrate that peroxidation of cancer cells in vitro can be monitored and evaluated by direct real‐time analysis of the volatile aldehydes produced. The combination of adopted methodology potentially has value for the study of other types of VOCs that may be produced by cellular damage.
Pitfall in Free‐Energy Simulations on Simplest Systems
Authors: Wong Kin‐Yiu , Xu Yuqing , Xu Liang 
Published: June 2017

AbstractFree‐energy simulation (FES) is widely used in science and engineering. Unconstrained FES (UFES, e. g., umbrella sampling with histogram binning) and constrained FES (CFES, e. g., blue‐moon sampling with mean‐force/thermodynamic integration) are two different types of FES. People prefer UFES to CFES, e. g., people correct constrained free‐energy profile (CFEP) to unconstrained FEP (UFEP), not the other way around. But remarkably, herein we show for a 1D free body subject to zero force, from an UFEP we find an infinitely‐high energy barrier. By contrast, we find no energy barrier from any CFEP. Besides, by providing in‐depth comparisons between UFEP and CFEP from the perspective of Jacobian scale factor, this work may also partially address recent issues on FES: (1) UFEP is preferred, but why do three recent papers conclude we should use CFEP for the transition‐state theory and why are these three papers not fully consistent with one another? (2) For relating UFEP to CFEP, why are there two different versions of Fixman term associated with velocity and momentum constraints, respectively? (3) How to normalize CFEP, for which the equation seems to be even unavailable?
Empirical dynamic modeling for beginners
Authors: Chang Chun‐Wei , Ushio Masayuki , Hsieh Chih‐hao 
Published: May 2017

AbstractNatural systems are often complex and dynamic (i.e. nonlinear), making them difficult to understand using linear statistical approaches. Linear approaches are fundamentally based on correlation. Thus, they are ill‐posed for dynamical systems, where correlation can occur without causation, and causation may also occur in the absence of correlation. “Mirage correlation” (i.e., the sign and magnitude of the correlation change with time) is a hallmark of nonlinear systems that results from state dependency. State dependency means that the relationships among interacting variables change with different states of the system. In recent decades, nonlinear methods that acknowledge state dependence have been developed. These nonlinear statistical methods are rooted in state space reconstruction, i.e. lagged coordinate embedding of time series data. These methods do not assume any set of equations governing the system but recover the dynamics from time series data, thus called empirical dynamic modeling (EDM). EDM bears a variety of utilities to investigating dynamical systems. Here, we provide a step‐by‐step tutorial for EDM applications with rEDM, a free software package written in the R language. Using model examples, we aim to guide users through several basic applications of EDM, including (1) determining the complexity (dimensionality) of a system, (2) distinguishing nonlinear dynamical systems from linear stochastic systems, and quantifying the nonlinearity (i.e. state dependence), (3) determining causal variables, (4) forecasting, (5) tracking the strength and sign of interaction, and (6) exploring the scenario of external perturbation. These methods and applications can be used to provide a mechanistic understanding of dynamical systems.