bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Measure of the Potential Impact of Hospital Community Health Activities on Population Health and Equity
Authors: Begun James W. , Kahn Linda M. , Cunningham Brooke A. , Malcolm Jan K. , Potthoff Sandra 
Published: December 2017

Context:
Many hospitals in the United States are exploring greater investment in community health activities that address upstream causes of poor health.

Objective:
Develop and apply a measure to categorize and estimate the potential impact of hospitals' community health activities on population health and equity.

Design, Setting, and Participants:
We propose a scale of potential impact on population health and equity, based on the cliff analogy developed by Jones and colleagues. The scale is applied to the 317 activities reported in the community health needs assessment implementation plan reports of 23 health care organizations in the Minneapolis-St Paul, Minnesota, metropolitan area in 2015.

Main Outcome Measure:
Using a 5-point ordinal scale, we assigned a score of potential impact on population health and equity to each community health activity.

Results:
A majority (50.2%) of health care organizations' community health activities are classified as addressing social determinants of health (level 4 on the 5-point scale), though very few (5.4%) address structural causes of health equity (level 5 on the 5-point scale). Activities that score highest on potential impact fall into the topic categories of “community health and connectedness” and “healthy lifestyles and wellness.” Lower-scoring activities focus on sick or at-risk individuals, such as the topic category of “chronic disease prevention, management, and screening.” Health care organizations in the Minneapolis-St Paul metropolitan area vary substantially in the potential impact of their aggregated community health activities.

Conclusions:
Hospitals can be significant contributors to investment in upstream community health programs. This article provides a scale that can be used not only by hospitals but by other health care and public health organizations to better align their community health strategies, investments, and partnerships with programming and policies that address the foundational causes of population health and equity within the communities they serve.
Low-Dose Insulin as an Antiscarring Therapy in Breast Surgery: A Randomized Controlled Trial
Authors: Hallam Marc-James , Pitt Elizabeth , Thomas Alexis , Nduka Charles 
Published: December 2017

Background:
The role of insulin in expediting wound healing is firmly established within the context of major trauma and burns; however, only limited clinical evidence exists as to its effects on scar formation. This study aims to build on previous laboratory work to examine the potential antiscarring properties of insulin in a clinical environment.

Methods:
Ninety-one patients undergoing bilateral aesthetic breast operations were recruited to receive low-dose insulin and placebo injections to the medial 3 cm of their submammary incisions within the context of a randomized, intrapatient, placebo-controlled trial, and scar quality was assessed at 3-, 6-, and 12-month reviews using the Manchester Scar Scale.

Results:
Across the cohort at 12-month review, the insulin-treated scars had lower scar scores (p = 0.055) compared with placebo. Subgroup analysis of individuals with heavier scars showed that median scar scores were significantly lower for the insulin-treated scars with regard to both scar contour (p = 0.048) and scar distortion (p = 0.045).

Conclusions:
Subcutaneous insulin injections reduced the appearance of scarring in this study compared with placebo. The greatest effect was seen in those participants who showed heavier scars and, as such, insulin has a role as an antiscarring therapy in individuals likely to be affected by heavier scarring. Further research is required to more precisely delineate which subjects may benefit most from this treatment.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, II.
The Boomerang Lift: A Three-Step Compartment-Based Approach to the Youthful Cheek
Authors: Schreiber Jillian E. , Terner Jordan , Stern Carrie S. , Beut Javier , Jelks Elizabeth B. , Jelks Glenn W. , Tepper Oren M. 
Published: December 2017

Summary:
Autologous fat grafting is an important tool for plastic surgeons treating the aging face. Malar augmentation with fat is often targeted to restore the youthful facial contour and provides support to the lower eyelid. The existence of distinct facial fat compartments suggests that a stepwise approach may be appropriate in this regard. The authors describe a three-step approach to malar augmentation using targeted deep malar fat compartmental augmentation, termed the “boomerang lift.” Clinical patients undergoing autologous fat grafting for malar augmentation were injected in three distinct deep malar fat compartments: the lateral sub–orbicularis oculi fat, the medial sub–orbicularis oculi fat, and the deep medial cheek (n = 9). Intraoperative three-dimensional images were taken at baseline and following compartmental injections (Canfield VECTRA H1). Images were overlaid between the augmented and baseline captures, and the three-dimensional surface changes were analyzed, which represented the resulting “augmentation zone.” Three-dimensional analysis demonstrated a unique pattern for the augmentation zone consistent across patients. The augmentation zone resembled a boomerang, with the short tail supporting the medial lower lid and the long tail extending laterally along the zygomatic arch. The upper border was restricted by the level of the nasojugal interface, and the lower border was defined medially by the nasolabial fold and laterally by the level of the zygomaticocutaneous ligament. Lateral and medial sub–orbicularis oculi fat injections defined the boundaries of the boomerang shape, and injection to the deep medial cheek provided maximum projection. This is the first description of deep malar augmentation zones in clinical patients. Three-dimensional surface imaging was ideal for analyzing the surface change in response to targeted facial fat grafting. The authors’ technique resulted in a reproducible surface shape, which they term the boomerang lift.
Temporally Distinct Regulation of Pathways Contributing to Cardiac Proteostasis During the Acute and Recovery Phases of Sepsis
Authors: Crowell Kristen T. , Moreno Samantha , Steiner Jennifer L. , Coleman Catherine S. , Soybel David I. , Lang Charles H. 
Published: December 2017

ABSTRACT

Background:
Cardiac dysfunction is a common manifestation of sepsis and is associated with early increases in inflammation and decreases in myocardial protein synthesis. However, little is known regarding the molecular mechanisms regulating protein homeostasis during the recovery phase after the removal of the septic nidus. Therefore, the purpose of this study was to investigate diverse signal transduction pathways that regulate myocardial protein synthesis and degradation.

Methods:
Adult male C57BL/6 mice were used to identify potential mechanisms mediating the acute (24 h) effect of cecal ligation and puncture as well as long-term changes that manifest during the chronic (10 days) recovery phase.

Results:
Sepsis acutely decreased cardiac protein synthesis that was associated with reduced phosphorylation of S6K1/S6 but not 4E-BP1. Sepsis also decreased proteasome activity, although with no change in MuRF1 and atrogin-1 mRNA expression. Sepsis acutely increased apoptosis (increased caspase-3 and PARP cleavage), autophagosome formation (increased LC3B-II), and canonical inflammasome activity (increased NLRP3, TMS1, cleaved caspase-1). In contrast, during the recovery phase, independent of a difference in food consumption, global protein synthesis was increased, the early repression in proteasome activity was restored to basal levels, whereas stimulation of apoptosis, autophagosome formation, and the canonical inflammasome pathway had abated. However, during recovery there was a selective stimulation of the noncanonical inflammasome pathway as evidenced by activation of caspase-11 with cleavage of Gasdermin D.

Conclusions:
These data demonstrate a temporally distinct homeostatic shift in the cardiac proteostatic response to acute infection and recovery.
Horner Syndrome as the Only Focal Neurologic Manifestation of Hypothalamic Hemorrhage
Authors: Sahin Cansu B. , Chaudhary Neeraj , Trobe Jonathan D. 
Published: December 2017

Abstract:
A 70-year-old woman suffered an anterior dorsal hypothalamic hemorrhage that caused an ipsilateral Horner syndrome (HS) as the only focal neurologic manifestation. This is only the second reported case of hypothalamic hemorrhage producing HS. Because HS was the sole focal neurologic manifestation, its confirmation with topical apraclonidine drops was a valuable clue toward prompt localization of the patient's confusional state.
OCR-Stats: Robust estimation and statistical testing of mitochondrial respiration activities using Seahorse XF Analyzer
Authors: Yépez Vicente A. , Kremer Laura S. , Iuso Arcangela , Gušić Mirjana , Kopajtich Robert , Koňaříková Eliška , Nadel Agnieszka , Wachutka Leonhard , Prokisch Holger , Gagneur Julien 
Published: December 2017

AbstractAccurate quantification of cellular and mitochondrial bioenergetic activity is of great interest in medicine and biology. Mitochondrial stress tests performed with Seahorse Bioscience XF Analyzers allow estimating different bioenergetic measures by monitoring oxygen consumption rates (OCR) of living cells in multi-well plates. However, studies of statistical best practices for determining OCR measurements and comparisons have been lacking so far. Therefore, we performed mitochondrial stress tests in 126 96-well plates involving 203 fibroblast cell lines to understand how OCR behaves across different biosamples, wells, and plates. We show that the noise of OCR is multiplicative, that outlier data points can concern individual measurements or all measurements of a well, and that the inter-plate variation is greater than intra-plate variation. Based on these insights, we developed a novel statistical method, OCR-Stats, that: i) robustly estimates OCR levels modeling multiplicative noise and automatically identifying outlier data points and outlier wells; and ii) performs statistical testing between samples, taking into account the different magnitudes of the between- and within-plates variations. This led to a significant reduction of the coefficient of variation across plates of basal respiration by 36% and of maximal respiration by 32%. Moreover, using positive and negative controls, we show that our statistical test outperforms existing methods, which either suffer from an excess of false positives (within-plates methods), or of false negatives (between-plates methods). Altogether, the aim of this study is to propose statistical good practices to support experimentalists in designing, analyzing, testing and reporting results of mitochondrial stress tests using this high throughput platform.
Three-dimensional cultured Liver-on-a-Chip with mature hepatocyte-like cells derived from human pluripotent stem cells
Authors: Kamei Ken-ichiro , Yoshioka Momoko , Terada Shiho , Tokunaga Yumie , Chen Yong 
Published: December 2017

AbstractLiver-on-a-Chip technology holds considerable potential for applications in drug screening and chemical-safety testing. To establish such platforms, functional hepatocytes are required; however, primary hepatocytes are commonly used, despite problems involving donor limitations, lot-to-lot variation, and unsatisfactory two-dimensional culture methods. Although human pluripotent stem cells (hPSCs) may represent a strong alternative contender to address the aforementioned issues, remaining technological challenges include the robust, highly efficient production of high-purity hepatic clusters. In addition, current Liver-on-a-Chip platforms are relatively complicated and not applicable for high-throughput experiments. Here, we develop a very simple Liver-on-a-Chip platform with mature and functional hepatocyte-like cells derived from hPSCs. To establish a method for hepatic differentiation of hPSCs, cells were first treated by inhibiting the phosphoinositide 3-kinase- and Rho-associated protein kinase-signaling pathways to stop self-renewal and improve survival, respectively, which enabled the formation of a well-defined endoderm and facilitated hepatocyte commitment. Next, a simple microfluidic device was used to create a three-dimensional (3D) culture environment that enhanced the maturation and function of hepatocyte-like cells by increasing the expression of both hepatic maturation markers and cytochrome P450. Finally, we confirmed improvements in hepatic functions, such as drug uptake/excretion capabilities, in >90% of 3D-matured hepatocyte-like cells by indocyanin green assay. These results indicated that the incorporation of hPSC-derived hepatocytes on our Liver-on-a-Chip platform may serve to enhance the processes involved in drug screening and chemical-safety testing.
Modeling Systemic Colorimetric Parameters as a Tool for Processing Images of Clumps of Toxic Cyanobacteria Targeted at Their Boundaries Detection
Authors: Bespalov Yu. G. , Nosov K. V. , Kabalyants P. S. 
Published: December 2017

AbstractGlobal climate change, along with other large-scale consequences of human impact upon the nature, increases the risk of biosafety threats associated with the disturbance of stability of communities of living organisms. In this regard, the topicality of the challenge of developing methods for monitoring and correcting homeostasis mechanisms that can support this stability is a problem of premium importance.The work aims at investigation of techniques of remote detection of toxic cyanobacteria clumps in water area, with the use of dynamical modeling.
Shape-related characteristics of age-related differences in subcortical structures
Authors: Madan Christopher R. 
Published: December 2017

AbstractOBJECTIVESWith an increasing aging population, it is important to gain a better understanding of biological markers of aging. Subcortical volume is known to differ with age; additionally considering shape-related characteristics may provide a better index of age-related differences in subcortical structure. Recently fractal dimensionality has been shown to be more sensitive to age-related differences, but this measure is borne out of mathematical principles, rather than quantifying a neurobiologically relevant characteristic directly. We considered four distinct measures of shape and how they relate to aging and fractal dimensionality: surface-to-volume ratio, sphericity, long-axis curvature, and surface texture.METHODSStructural MRIs from two samples, with a combined sample size of over 600 healthy adults across the adult lifespan, were used to measure age-related differences in the structure of the thalamus, putamen, caudate, and hippocampus. For each structure, volume and fractal dimensionality were calculated, as well as each of the four distinct shape measures. These measures were then examined in their utility in explaining age-related variability in brain structure.RESULTSThe four shape measures were able to account for 80-90% of the variance in fractal dimensionality, indicating that these measures were sensitive to the same shape characteristics. Of the distinct shape measures, surface-to-volume ratio was the most sensitive aging biomarker.CONCLUSIONThough volume is often used to characterize inter-individual differences in subcortical structures, our results demonstrate that additional measures can be useful complements to volumetry. Our results indicate that shape characteristics of subcortical structures are useful biological markers of healthy aging.
Estimating the functional dimensionality of neural representations
Authors: Ahlheim Christiane , Love Bradley C. 
Published: December 2017

AbstractRecent advances in multivariate fMRI analysis stress the importance of information inherent to voxel patterns. Key to interpreting these patterns is estimating the underlying dimensionality of neural representations. Dimensions may correspond to psychological dimensions, such as length and orientation, or involve other coding schemes. Unfortunately, the noise structure of fMRI data inflates dimensionality estimates and thus makes it difficult to assess the true underlying dimensionality of a pattern. To address this challenge, we developed a novel approach to identify brain regions that carry reliable task-modulated signal and to derive an estimate of the signal’s functional dimensionality. We combined singular value decomposition with cross-validation to find the best low-dimensional projection of a pattern of voxel-responses at a single-subject level. Goodness of the low-dimensional reconstruction is measured as Pearson correlation with a test set, which allows to test for significance of the low-dimensional reconstruction across participants. Using hierarchical Bayesian modeling, we derive the best estimate and associated uncertainty of underlying dimensionality across participants. We validated our method on simulated data of varying underlying dimensionality, showing that recovered dimensionalities match closely true dimensionalities. We then applied our method to three published fMRI data sets all involving processing of visual stimuli. The results highlight three possible applications of estimating the functional dimensionality of neural data. Firstly, it can aid evaluation of model-based analyses by revealing which areas express reliable, task-modulated signal that could be missed by specific models. Secondly, it can reveal functional differences across brain regions. Thirdly, knowing the functional dimensionality allows assessing task-related differences in the complexity of neural patterns.
Similar clinical improvement and maintenance after rTMS at 5 Hz using a simple vs. complex protocol in Alzheimer’s disease
Authors: Alcalá-Lozano R. , Morelos-Santana E. , Cortés-Sotres J.F. , Garza-Villarreal E. A. , Sosa-Ortiz A. L. , Gonzalez-Olvera J. J. 
Published: December 2017

AbstractBrackgroundCurrent treatments for Alzheimer’s disease (AD) have a limited clinical response and methods, such as repetitive transcranial magnetic stimulation (rTMS), are being studied as possible treatments for the clinical symptoms with positive results. However, there is still seldom information on the type of rTMS protocols that deliver the best clinical improvement in AD.ObjetiveTo compare the clinical response between a simple stimulation protocol on the left dorsolateral prefrontal cortex (lDLPFC) against a complex protocol using six regions of interest.Methods19 participants were randomized to receive any of the protocols. The analysis of repeated measures evaluated the change.ResultsBoth protocols were equally proficient at improving cognitive function, behavior and functionality after 3 weeks of treatment, and the effects were maintained for 4 weeks more without treatment.ConclusionWe suggest rTMS on the lDLPFC could be enough to provide a clinical response, and the underlying mechanisms should be studied.
Phasic Activation of Ventral Tegmental, but not Substantia Nigra, Dopamine Neurons Promotes Model-Based Pavlovian Reward Learning
Authors: Keiflin R. , Pribut H.J. , Shah N.B. , Janak P.H. 
Published: December 2017

ABSTRACTDopamine (DA) neurons in the ventral tegmental area (VTA) and substantia nigra (SNc) encode reward prediction errors (RPEs) and are proposed to mediate error-driven learning. However the learning strategy engaged by DA-RPEs remains controversial. Model-free associations imbue cue/actions with pure value, independently of representations of their associated outcome. In contrast, model-based associations support detailed representation of anticipated outcomes. Here we show that although both VTA and SNc DA neuron activation reinforces instrumental responding, only VTA DA neuron activation during consumption of expected sucrose reward restores error-driven learning and promotes formation of a new cue→sucrose association. Critically, expression of VTA DA-dependent Pavlovian associations is abolished following sucrose devaluation, a signature of model-based learning. These findings reveal that activation of VTA-or SNc-DA neurons engages largely dissociable learning processes with VTA-DA neurons capable of participating in model-based predictive learning, while the role of SNc-DA neurons appears limited to reinforcement of instrumental responses.
Derivation and validation of a VISITAG™-guided contact force ablation protocol for pulmonary vein isolation
Authors: Tomlinson David R. 
Published: December 2017

AbstractAims Following radiofrequency (RF) pulmonary vein isolation (PVI), atrial fibrillation (AF) recurrence mediated by recovery of pulmonary vein (PV) conduction is common. I examined whether comparative VISITAG™ (Biosense Webster Inc.) data analysis at sites showing intra-procedural recovery of PV conduction versus acutely durable ablation could inform the derivation of a more effective VISITAG™-guided contact force (CF) PVI protocol.Methods and results Retrospective analysis of VISITAG™ Module annotated ablation site data in 10 consecutive patients undergoing CF-guided PVI without active VISITAG™ guidance. Employing 2mm positional stability range and lenient CF filter (force-over-time 10%, minimum 2g), inter-ablation site distance >10-12mm, adjacent 0g-minimum CF and short RF duration (3-5s) were associated with intra-procedural recovery of PV conduction. A VISITAG™-guided CF PVI protocol was derived employing ≤6mm inter-ablation site distances, minimum target ablation site duration ≥9s / force time integral (FTI) 100gs and 100% 1g-minimum CF filter. Seventy-two consecutive VISITAG™-guided CF PVI procedures were then undertaken using this protocol, with PVI achieved in all utilising 23.8[8.4] minutes total RF (30W, 48°C, 17ml/min, continuous RF application). Following protocol completion, acute intra-procedural spontaneous / dormant recovery of PV conduction requiring touch-up RF occurred in 1.4% / 1.8% of PVs, respectively. At 14[5] months’ follow-up in all 34 patients with paroxysmal AF ≥6 months’ post-ablation, 30 (88%) were free from atrial arrhythmia, off class I/III anti-arrhythmic medication.Conclusion VISITAG™ provides means to identify and then avoid factors associated with intra-procedural recovery of PV conduction. This VISITAG™ Module-guided CF PVI protocol demonstrated excellent intra-procedural and long-term efficacy.Condensed abstract Following CF-guided PVI, retrospective VISITAG™ Module analyses permitted the identification of ablation parameters associated with intra-procedural recovery of PV conduction. The derived VISITAG™ Module-guided CF PVI protocol employed short over RF duration yet proved efficient at achieving PVI acutely, with long-term follow-up demonstrating high clinical efficacy.
Application of the fluctuation theorem for non-invasive force measurement in living neuronal axons
Authors: Hayashi Kumiko , Tsuchizawa Yuta , Iwaki Mitsuhiro , Okada Yasushi 
Published: December 2017

AbstractAlthough its importance is recently widely accepted, force measurement has been difficult in living biological systems, mainly due to the lack of the versatile non-invasive force measurement methods. The fluctuation theorem, which represents the thermodynamic properties of small fluctuating non-equilibrium systems, has been applied to the analysis of the thermodynamic properties of motor proteinsin vitro. Here, we extend it to the axonal transport (displacement) of endosomes. The distribution of the displacement fluctuation had three or four distinct peaks around multiples of a unit value, which the fluctuation theorem can convert into the drag force exerted on the endosomes. The results demonstrated that a single cargo vesicle is conveyed by one to three or four units of force production.