bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell engineering with microfluidic squeezing preserves functionality of primary immune cells in vivo
Authors: DiTommaso Tia , Cole Julie M. , Cassereau Luke , Buggé Joshua A. , Hanson Jacquelyn L. Sikora , Bridgen Devin T. , Stokes Brittany D. , Loughhead Scott M. , Beutel Bruce A. , Gilbert Jonathan B. , Nussbaum Kathrin , Sorrentino Antonio , Toggweiler Janine , Schmidt Tobias , Gyuelveszi Gabor , Bernstein Howard , Sharei Armon
Published: October 2018

Significance

Ex vivo manipulation of primary cells is critical to the success of this emerging generation of cell-based therapies, such as chimeric antigen receptor T cells for the treatment of cancer and CRISPR for the correction of developmental diseases. However, the limitations of existing delivery approaches may dramatically restrict the impact of genetic engineering to study and treat disease. In this paper, we compared electroporation to a microfluidic membrane deformation technique termed “squeezing” and found that squeezed cells had dramatically fewer side effects than electroporation and gene expression profiles similar to those of unmanipulated cells. The significant differences in outcomes from the two techniques underscores the importance of understanding the impact of intracellular delivery methods on cell function for research and clinical applications.
Universality of jamming of nonspherical particles
Authors: Brito Carolina , Ikeda Harukuni , Urbani Pierfrancesco , Wyart Matthieu , Zamponi Francesco
Published: October 2018

Significance

The jamming transition is a key property of granular materials, including sand and dense suspensions. In the generic situation of nonspherical particles, its scaling properties are not completely understood. Previous empirical and theoretical work in ellipsoids and spherocylinders indicates that both structural and vibrational properties are fundamentally affected by shape. Here we explain these observations using a combination of marginal stability arguments and the replica method. We unravel a universality class for particles with internal degrees of freedom and derive how the structure of packings and their vibrations scale as the particles evolve toward spheres.
Cow's milk as a post‐exercise recovery drink: implications for performance and health
Authors: James Lewis J. , Stevenson Emma J. , Rumbold Penny L. S. , Hulston Carl J.
Published: October 2018

Post‐exercise recovery is a multi‐facetted process that will vary depending on the nature of the exercise, the time between exercise sessions and the goals of the exerciser. From a nutritional perspective, the main considerations are: (1) optimisation of muscle protein turnover; (2) glycogen resynthesis; (3) rehydration; (4) management of muscle soreness; (5) appropriate management of energy balance. Milk is approximately isotonic (osmolality of 280–290 mosmol/kg), and the mixture of high quality protein, carbohydrate, water and micronutrients (particularly sodium) make it uniquely suitable as a post‐exercise recovery drink in many exercise scenarios. Research has shown that ingestion of milk post‐exercise has the potential to beneficially impact both acute recovery and chronic training adaptation. Milk augments post‐exercise muscle protein synthesis and rehydration, can contribute to post‐exercise glycogen resynthesis, and attenuates post‐exercise muscle soreness/function losses. For these aspects of recovery, milk is at least comparable and often out performs most commercially available recovery drinks, but is available at a fraction of the cost, making it a cheap and easy option to facilitate post‐exercise recovery. Milk ingestion post‐exercise has also been shown to attenuate subsequent energy intake and may lead to more favourable body composition changes with exercise training. This means that those exercising for weight management purposes might be able to beneficially influence post‐exercise recovery, whilst maintaining the energy deficit created by exercise.
Ventricular–subventricular zone fractones are speckled basement membranes that function as a neural stem cell niche
Authors: Sato Yuya , Kiyozumi Daiji , Futaki Sugiko , Nakano Itsuko , Shimono Chisei , Kaneko Naoko , Ikawa Masahito , Okabe Masaru , Sawamoto Kazunobu , Sekiguchi Kiyotoshi
Published: October 2018

Neural stem cells (NSCs) are retained in the adult ventricular–subventricular zone (V-SVZ), a specialized neurogenic niche with a unique cellular architecture. It currently remains unclear whether or how NSCs utilize basement membranes (BMs) in this niche. Here, we examine the molecular compositions and functions of BMs in the adult mouse V-SVZ. Whole-mount V-SVZ immunostaining revealed that fractones, which are fingerlike processes of extravascular BMs, are speckled BMs unconnected to the vasculature, and differ in their molecular composition from vascular BMs. Glial fibrillary acidic protein (GFAP)-positive astrocytes and NSCs produce and adhere to speckled BMs. Furthermore, Gfap-Cre-mediated Lamc1flox(E1605Q)knockin mice, in which integrin-binding activities of laminins are specifically nullified in GFAP-positive cells, exhibit a decreased number and size of speckled BMs and reduced in vitro neurosphere-forming activity. Our results reveal niche activities of fractones/speckled BMs for NSCs and provide molecular insights into how laminin–integrin interactions regulate NSCs in vivo.
Reductions in ATPase activity, actin sliding velocity, and myofibril stability yield muscle dysfunction inDrosophilamodels of myosin-based Freeman–Sheldon syndrome
Authors: Rao Deepti S. , Kronert William A. , Guo Yiming , Hsu Karen H. , Sarsoza Floyd , Bernstein Sanford I.
Published: October 2018

Using Drosophila melanogaster, we created the first animal models for myosin-based Freeman–Sheldon syndrome (FSS), a dominant form of distal arthrogryposis defined by congenital facial and distal skeletal muscle contractures. Electron microscopy of homozygous mutant indirect flight muscles showed normal (Y583S) or altered (T178I, R672C) myofibril assembly followed by progressive disruption of the myofilament lattice. In contrast, all alleles permitted normal myofibril assembly in the heterozygous state but caused myofibrillar disruption during aging. The severity of myofibril defects in heterozygotes correlated with the level of flight impairment. Thus our Drosophila models mimic the human condition in that FSS mutations are dominant and display varied degrees of phenotypic severity. Molecular modeling indicates that the mutations disrupt communication between the nucleotide-binding site of myosin and its lever arm that drives force production. Each mutant myosin showed reduced in vitro actin sliding velocity, with the two more severe alleles significantly decreasing the catalytic efficiency of actin-activated ATP hydrolysis. The observed reductions in actin motility and catalytic efficiency may serve as the mechanistic basis of the progressive myofibrillar disarray observed in the Drosophila models as well as the prolonged contractile activity responsible for skeletal muscle contractures in FSS patients.
DrugThatGene: integrative analysis to streamline the identification of druggable genes, pathways and protein complexes from CRISPR screens
Authors: Canver Matthew C , Bauer Daniel E , Maeda Takahiro , Pinello Luca
Published: October 2018

Motivation

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) nuclease system has allowed for high-throughput, large scale pooled screens for functional genomic studies. To aid in the translation of functional genomics to therapeutics, we developed DrugThatGene (DTG) as a web-based application that streamlines analysis of potential therapeutic targets identified from functional genetic screens.

Results

Starting from a gene list as input, DTG offers automated identification of small molecules along with supporting information from human genetic and other relevant databases. Furthermore, DTG aids in the identification of common biological pathways and protein complexes in conjunction with associated small molecule inhibitors. Taken together, DTG aims to expedite the identification of small molecules from the abundance of functional genetic data generated from CRISPR screens.

Availability and implementation

DTG is an open-source and free software available as a website at http://drugthatgene.pinellolab.org. Source code is available at: https://github.com/pinellolab/DrugThatGene, which can be downloaded in order to run DTG locally.
Bastion3: a two-layer ensemble predictor of type III secreted effectors
Authors: Wang Jiawei , Li Jiahui , Yang Bingjiao , Xie Ruopeng , Marquez-Lago Tatiana T , Leier André , Hayashida Morihiro , Akutsu Tatsuya , Zhang Yanju , Chou Kuo-Chen , Selkrig Joel , Zhou Tieli , Song Jiangning , Lithgow Trevor
Published: October 2018

Motivation

Type III secreted effectors (T3SEs) can be injected into host cell cytoplasm via type III secretion systems (T3SSs) to modulate interactions between Gram-negative bacterial pathogens and their hosts. Due to their relevance in pathogen–host interactions, significant computational efforts have been put toward identification of T3SEs and these in turn have stimulated new T3SE discoveries. However, as T3SEs with new characteristics are discovered, these existing computational tools reveal important limitations: (i) most of the trained machine learning models are based on the N-terminus (or incorporating also the C-terminus) instead of the proteins’ complete sequences, and (ii) the underlying models (trained with classic algorithms) employed only few features, most of which were extracted based on sequence-information alone. To achieve better T3SE prediction, we must identify more powerful, informative features and investigate how to effectively integrate these into a comprehensive model.

Results

In this work, we present Bastion3, a two-layer ensemble predictor developed to accurately identify type III secreted effectors from protein sequence data. In contrast with existing methods that employ single models with few features, Bastion3 explores a wide range of features, from various types, trains single models based on these features and finally integrates these models through ensemble learning. We trained the models using a new gradient boosting machine, LightGBM and further boosted the models’ performances through a novel genetic algorithm (GA) based two-step parameter optimization strategy. Our benchmark test demonstrates that Bastion3 achieves a much better performance compared to commonly used methods, with an ACC value of 0.959, F-value of 0.958, MCC value of 0.917 and AUC value of 0.956, which comprehensively outperformed all other toolkits by more than 5.6% in ACC value, 5.7% in F-value, 12.4% in MCC value and 5.8% in AUC value. Based on our proposed two-layer ensemble model, we further developed a user-friendly online toolkit, maximizing convenience for experimental scientists toward T3SE prediction. With its design to ease future discoveries of novel T3SEs and improved performance, Bastion3 is poised to become a widely used, state-of-the-art toolkit for T3SE prediction.

Availability and implementation

http://bastion3.erc.monash.edu/

Contact

selkrig@embl.de or wyztli@163.com or or trevor.lithgow@monash.edu

Supplementary information

Supplementary data are available at Bioinformatics online.
Effects of Touch Force Profiles and Waveforms of Electrostatic Tactile Feedback on Touchscreen Pan Operation
Authors: Yan Xuezhi , Li Ruige , Sun Xiaoying , Liu Guohong
Published: October 2018

Electrostatic tactile feedback has an important role in improving touchscreen operations and user experience. In this paper, panning performance under different forces and different waveforms were explored using subjective and objective experiments. The effects of electrostatic tactile feedback under one linear force and three non-linear force profiles with the fixed waveform were studied. The results indicated that panning accuracy, efficiency and user experience under exponential force was superior to those under linear, quadratic or logarithmic forces. Second, the effects of four different waveforms under exponential force were studied. Results indicated that panning performance was better with square wave, compared to those with sinusoidal, triangular or sawtooth waves. The relationship between panning time and index of panning difficulties was also explored and found to be in agreement with the Steering law and Meyer’s law, with correlations of 0.9395 and 0.9397, respectively. The results suggest ways for designing touchscreens with tactile feedback that is useful in both research and end-user communities.
Measuring extractive institutions: colonial trade and price gaps in French Africa
Authors: Tadei Federico
Published: October 2018

Colonial extractive institutions are often blamed for current African underdevelopment. Yet, since colonial extraction is hard to quantify, the magnitude of this phenomenon remains unclear. In this paper, I use new archival data to estimate colonial extraction through trade, measured as the gap between prices that the monopsonistic French trading companies paid to African producers and prices that should have been paid in a counterfactual competitive market. The results show that African prices were only a small fraction of competitive prices, implying an annual loss of almost 2 percent of GDP during colonial rule.
On the Random Wave Conjecture for Eisenstein Series
Authors: Djanković Goran , Khan Rizwanur
Published: October 2018

We obtain an asymptotic for the regularized 4th moment of the Eisenstein series for the full modular group, in agreement with the Random Wave Conjecture.
Local discoveries and technological relatedness: the role of MNEs, imports and domestic capabilities
Authors: Lo Turco Alessia , Maggioni Daniela
Published: October 2018

We explore the role of intra- and extra-regional product-specific capabilities in the introduction of local discoveries—products new to the firm and to its local market—by Turkish manufacturing firms. We find that product discoveries in a NUTS3 region are favoured by their technological proximity to the product mix of co-located foreign firms. Proximity to co-located domestic firms and local imports does not play any role. The high intensity of local discoveries in novel and exclusive capabilities which foreign affiliates bring into the local economy drives our findings. Finally, we show that the importance of knowledge spilling from foreign affiliates depends on their insidership in the local market, on their product-specific knowledge advantage and on local firms’ absorptive capacity.
Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on the Role of Prophylactic Anticonvulsants in the Treatment of Adults with Metastatic Brain Tumors
Authors: Chen Clark C , Rennert Robert C , Olson Jeffrey J
Published: October 2018

TARGET POPULATIONS

Adults with solid brain metastases who have not experienced a seizure.

QUESTION 1

Do prophylactic antiepileptic drugs (AEDs) decrease the risk of seizures in nonsurgical patients with brain metastases who are otherwise seizure-free?

RECOMMENDATION

Level 3: Prophylactic AEDs are not recommended for patients with brain metastases who did not undergo surgical resection and are otherwise seizure-free.

QUESTION 2

Do prophylactic AEDs decrease the risk of seizures in patients with brain metastases and no prior history of seizures in the postoperative setting?

RECOMMENDATION

Level 3: Routine postcraniotomy AED use for seizure-free patients with brain metastases is not recommended.

The full guideline can be found at: https://www.cns.org/guidelines/guidelines-treatment-adults-metastatic-brain-tumors/chapter_8.
Year 2 of Affordable Care Act Qualified Health Plans (QHPs) in a Medicaid Nonexpansion State: QHPs Associated With Viral Suppression for Virginia AIDS Drug Assistance Program Clients
Authors: McManus Kathleen A , Rhodes Anne , Yerkes Lauren , Engelhard Carolyn L , Ingersoll Karen S , Dillingham Rebecca
Published: October 2018

Background

For year 1 of the Affordable Care Act (ACA), Virginia AIDS Drug Assistance Program (ADAP) clients with Qualified Health Plans (QHPs) achieved a higher rate of viral suppression. This study characterizes the demographic and health care delivery factors associated with QHP enrollment in year 2 and assesses the relationship between 2015 QHP coverage and HIV viral suppression.

Methods

The cohort included Virginia ADAP clients who were eligible for ADAP-funded QHPs. Data were collected from 2014 to 2015. Multivariable binary logistic regression was conducted to assess the association of demographic and health care delivery factors with QHP enrollment and viral suppression.

Results

In year 2, 63% of the cohort (n = 4631) enrolled in QHPs; 2015 ADAP-funded QHP enrollment was associated with 2014 ADAP-funded QHP (adjusted odds ratio [aOR], 111.11; 95% confidence interval [CI], 90.91–166.67), 2014 engagement in care (aOR, 2.16; 95% CI, 1.65–2.82), age (P < .001), race/ethnicity (P = .03), financial status (P < .001), and region (P < .001). For clients engaged in care (n = 2501), viral suppression was higher (83.3%) for those with ADAP-funded QHP coverage than for those who received medications from ADAP (79.9%). In multivariable binary logistic regression, achieving viral suppression was associated with 2015 QHP coverage (aOR, 1.27; 95% CI, 1.01–1.60), an initially undetectable viral load (aOR, 2.69; 95% CI, 2.13–3.39), gender (P = .03), age (P = .01), no AIDS diagnosis (aOR, 1.41; 95% CI, 1.12–1.78), financial status (P = .004), and region (P < .001).

Conclusions

Virginia ADAP client 2015 QHP enrollment increased compared with year 1 and varied based on demographic and health care delivery factors. QHP coverage was again associated with viral suppression, an essential outcome for individuals and for public health.
Multi-site Pain Is Associated with Long-term Patient-Reported Outcomes in Older Adults with Persistent Back Pain
Authors: Rundell Sean D , Patel Kushang V , Krook Melissa A , Heagerty Patrick J , Suri Pradeep , Friedly Janna L , Turner Judith A , Deyo Richard A , Bauer Zoya , Nerenz David R , Avins Andrew L , Nedeljkovic Srdjan S , Jarvik Jeffrey G
Published: October 2018

Objective

To estimate the prevalence of co-occurring pain sites among older adults with persistent back pain and associations of multisite pain with longitudinal outcomes.

Design

Secondary analysis of a cohort study.

Setting

Three integrated health systems in the United States.

Subjects

Eight hundred ninety-nine older adults with persistent back pain.

Methods

Participants reported pain in the following sites: stomach, arms/legs/joints, headaches, neck, pelvis/groin, and widespread pain. Over 18 months, we measured back-related disability (Roland Morris, scored 0–24), pain intensity (11-point numerical rating scale), health-related quality of life (EuroQol-5D [EQ-5D], utility from 0–1), and falls in the past three weeks. We used mixed-effects models to test the association of number and type of pain sites with each outcome.

Results

Nearly all (N = 839, 93%) respondents reported at least one additional pain site. There were 216 (24%) with one additional site and 623 (69%) with multiple additional sites. The most prevalent comorbid pain site was the arms/legs/joints (N = 801, 89.1%). Adjusted mixed-effects models showed that for every additional pain site, RMDQ worsened by 0.65 points (95% confidence interval [CI] = 0.43 to 0.86), back pain intensity increased by 0.14 points (95% CI = 0.07 to 0.22), EQ-5D worsened by 0.012 points (95% CI = –0.018 to –0.006), and the odds of falling increased by 27% (odds ratio = 1.27, 95% CI = 1.12 to 1.43). Some specific pain sites (extremity pain, widespread pain, and pelvis/groin pain) were associated with greater long-term disability.

Conclusions

Multisite pain is common among older adults with persistent back pain. Number of pain sites was associated with all outcomes; individual pain sites were less consistently associated with outcomes.
Network Analysis Reveals Which Negative Symptom Domains Are Most Central in Schizophrenia vs Bipolar Disorder
Authors: Strauss Gregory Paul , Esfahlani Farnaz Zamani , Kirkpatrick Brian , Allen Daniel N , Gold James M , Visser Katherine Frost , Sayama Hiroki
Published: October 2018

Network analysis was used to examine how densely interconnected individual negative symptom domains are, whether some domains are more central than others, and whether sex influenced network structure. Participants included outpatients with schizophrenia (SZ; n = 201), a bipolar disorder (BD; n = 46) clinical comparison group, and healthy controls (CN; n = 27) who were rated on the Brief Negative Symptom Scale. The mutual information measure was used to construct negative symptom networks. Groups were compared on macroscopic network properties to evaluate overall network connectedness, and microscopic properties to determine which domains were most central. Macroscopic analyses indicated that patients with SZ had a less densely connected negative symptom network than BD or CN groups, and that males with SZ had less densely connected networks than females. Microscopic analyses indicated that alogia and avolition were most central in the SZ group, whereas anhedonia was most central in BD and CN groups. In addition, blunted affect, alogia, and asociality were most central in females with SZ, and alogia and avolition were most central in males with SZ. These findings suggest that negative symptoms may be highly treatment resistant in SZ because they are not very densely connected. Less densely connected networks may make treatments less likely to achieve global reductions in negative symptoms because individual domains function in isolation with little interaction. Sex differences in centralities suggest that the search for pathophysiological mechanisms and targeted treatment development should be focused on different sets of symptoms in males and females.
Phylogenomic Signatures of Ancient Introgression in a Rogue Lineage of Darters (Teleostei: Percidae)
Authors: MacGuigan Daniel J , Near Thomas J
Published: October 2018

Evolutionary history is typically portrayed as a branching phylogenetic tree, yet not all evolution proceeds in a purely bifurcating manner. Introgressive hybridization is one process that results in reticulate evolution. Most known examples of genome-wide introgression occur among closely related species with relatively recent common ancestry; however, we present evidence for ancient hybridization and genome-wide introgression between major stem lineages of darters, a species-rich clade of North American freshwater fishes. Previous attempts to resolve the relationships of darters have been confounded by the uncertain phylogenetic resolution of the lineage Allohistium. In this study, we investigate the phylogenomics of darters, specifically the relationships of Allohistium, through analyses of approximately 30,000 RADseq loci sampled from 112 species. Our phylogenetic inferences are based on traditional approaches in combination with strategies that accommodate reticulate evolution. These analyses result in a novel phylogenetic hypothesis for darters that includes ancient introgression between Allohistium and other two major darter lineages, minimally occurring 20 million years ago. Darters offer a compelling case for the necessity of incorporating phylogenetic networks in reconstructing the evolutionary history of diversification in species-rich lineages. We anticipate that the growing wealth of genomic data for clades of non-model organisms will reveal more examples of ancient hybridization, eventually requiring a re-evaluation of how evolutionary history is visualized and utilized in macroevolutonary investigations.
Spontaneous Breathing in Early Acute Respiratory Distress Syndrome: Insights From the Large Observational Study to UNderstand the Global Impact of Severe Acute Respiratory FailurE Study*
Authors: van Haren Frank , Pham Tài , Brochard Laurent , Bellani Giacomo , Laffey John , Dres Martin , Fan Eddy , Goligher Ewan C. , Heunks Leo , Lynch Joan , Wrigge Hermann , McAuley Danny
Published: October 2018

Objectives:

To describe the characteristics and outcomes of patients with acute respiratory distress syndrome with or without spontaneous breathing and to investigate whether the effects of spontaneous breathing on outcome depend on acute respiratory distress syndrome severity.

Design:

Planned secondary analysis of a prospective, observational, multicentre cohort study.

Setting:

International sample of 459 ICUs from 50 countries.

Patients:

Patients with acute respiratory distress syndrome and at least 2 days of invasive mechanical ventilation and available data for the mode of mechanical ventilation and respiratory rate for the 2 first days.

Interventions:

Analysis of patients with and without spontaneous breathing, defined by the mode of mechanical ventilation and by actual respiratory rate compared with set respiratory rate during the first 48 hours of mechanical ventilation.

Measurements and Main Results:

Spontaneous breathing was present in 67% of patients with mild acute respiratory distress syndrome, 58% of patients with moderate acute respiratory distress syndrome, and 46% of patients with severe acute respiratory distress syndrome. Patients with spontaneous breathing were older and had lower acute respiratory distress syndrome severity, Sequential Organ Failure Assessment scores, ICU and hospital mortality, and were less likely to be diagnosed with acute respiratory distress syndrome by clinicians. In adjusted analysis, spontaneous breathing during the first 2 days was not associated with an effect on ICU or hospital mortality (33% vs 37%; odds ratio, 1.18 [0.92–1.51]; p = 0.19 and 37% vs 41%; odds ratio, 1.18 [0.93–1.50]; p = 0.196, respectively ). Spontaneous breathing was associated with increased ventilator-free days (13 [0–22] vs 8 [0–20]; p = 0.014) and shorter duration of ICU stay (11 [6–20] vs 12 [7–22]; p = 0.04).

Conclusions:

Spontaneous breathing is common in patients with acute respiratory distress syndrome during the first 48 hours of mechanical ventilation. Spontaneous breathing is not associated with worse outcomes and may hasten liberation from the ventilator and from ICU. Although these results support the use of spontaneous breathing in patients with acute respiratory distress syndrome independent of acute respiratory distress syndrome severity, the use of controlled ventilation indicates a bias toward use in patients with higher disease severity. In addition, because the lack of reliable data on inspiratory effort in our study, prospective studies incorporating the magnitude of inspiratory effort and adjusting for all potential severity confounders are required.
Esophageal Doppler Can Predict Fluid Responsiveness Through End-Expiratory and End-Inspiratory Occlusion Tests
Authors: Dépret François , Jozwiak Mathieu , Teboul Jean-Louis , Alphonsine Jean-Emmanuel , Richard Christian , Monnet Xavier
Published: October 2018

Objectives:

To assess whether, in patients under mechanical ventilation, fluid responsiveness is predicted by the effects of short respiratory holds on cardiac index estimated by esophageal Doppler.

Design:

Prospective, monocentric study.

Setting:

Medical ICU.

Patients:

Twenty-eight adult patients with acute circulatory failure and a decision of the clinicians in charge to administer fluids.

Interventions:

Before and after infusing 500 mL of saline, we measured cardiac index estimated by esophageal Doppler before and during the last 5 seconds of successive 15-second end-inspiratory occlusion and end-expiratory occlusion, separated by 1 minute. Patients in whom volume expansion increased cardiac index measured by transpulmonary thermodilution greater than or equal to 15% were defined as “fluid responders.” Cardiac index measured by the Pulse Contour Cardiac Output device (from pulse contour analysis or transpulmonary thermodilution) was used as the reference.

Measurements and Main Results:

End-expiratory occlusion increased cardiac index estimated by esophageal Doppler more in responders than in nonresponders (8% ± 2% vs 3% ± 1%, respectively; p < 0.0001) and end-inspiratory occlusion decreased cardiac index estimated by esophageal Doppler more in responders than in nonresponders (–8% ± 5% vs –4% ± 2%, respectively; p = 0.0002). Fluid responsiveness was predicted by the end-expiratory occlusion induced percent change in cardiac index estimated by esophageal Doppler with an area under the receiver operating characteristic curve of 1.00 (95% CI, 0.88–1.00) and a threshold value of 4% increase in cardiac index estimated by esophageal Doppler. It was predicted by the sum of absolute values of percent changes in cardiac index estimated by esophageal Doppler during both occlusions with a similar area under the receiver operating characteristic curve (0.99 [0.86–1.00]) and with a threshold of 9% change in cardiac index estimated by esophageal Doppler, which is compatible with the esophageal Doppler precision.

Conclusions:

If the absolute sum of the percent change in cardiac index estimated by esophageal Doppler induced by two successive end-inspiratory occlusion and end-expiratory occlusion maneuvers is greater than 9%, it is likely that a 500 mL fluid infusion will increase cardiac output. This diagnostic threshold is higher than if only end-expiratory occlusion induced percent changes in cardiac index estimated by esophageal Doppler are taken into account.
A reason to renovate: The association between hospital age of plant and value-based purchasing performance
Authors: Beauvais Brad , Richter Jason P. , Kim Forest S. , Palmer Erin L. , Spear Bryan L. , Turner Robert C.
Published: October 2018

Background/Purpose

Value-based purchasing (VBP) is increasing in influence in the health care industry; however, questions remain regarding the structural factors associated with improved performance. This study evaluates the association between age of hospital infrastructure and VBP outcomes.

Methodology

Data on 1,911 hospitals from three sources (the American Hospital Association Annual Survey Database, the American Hospital Association DataViewer Financial Module, and the Centers for Medicare & Medicaid Services Hospital VBP Total Performance Scores data set) were evaluated. Age of health care facilities was represented by the “average age of plant” financial ratio. VBP performance was measured by an aggregate Total Performance Score composed of four equally weighted domains, including Efficiency and Cost Reduction, Clinical Care, Patient- and Caregiver-Centered Experience, and Patient Safety. We hypothesize that average age of plant is negatively correlated with each of these measures.

Results

Hospitals within the lowest quartile of average age of plant (0–8.13 years) were found to have a total Performance Score of 2.35 points higher than hospitals with a an average age of plant in the fourth quartile (14.63 years and above; R
2 = 21.5%; p < .001) while controlling for hospital ownership, size, teaching status, geographic location, service mix, case mix, length of stay, community served, and labor force relative cost. Comparable results were found within the VBP domains, specifically for Clinical Care (β = 4.09, p < .001) and Patient Experience (β = 3.41, p < .001). Findings for the Patient Safety and Efficiency domains were not significant. A secondary and more granular examination of capitalized assets indicates organizations with higher building asset accumulated depreciation per bed in service were associated with lower total performance (β = −.25, p < .001), Clinical Care (β = −.31, p < .05), and Patient Experience scores (β = −.45, p < .001).

Conclusions

The results of this study provide evidence of an inverse association between a hospital’s age of plant and specific elements of VBP performance.

Practice Implications

To date, no studies have investigated the relationship between hospital age of plant and value-based care. The results of our study may serve as supportive foundational evidence for health care leaders to target future capital investments to improve VBP outcomes.
INCREASED SYSTEMIC HEPARANASE IN RETINAL VEIN OCCLUSION IS ASSOCIATED WITH ACTIVATION OF INFLAMMATION AND THROMBOPHILIA
Authors: Hu Yijun , Yu Yang , Bu Zhanyun , Cun Biyun , Gong Yi , Li Dongli , Li Jianhua , Lu Li , Li Guodong , Yuan Ling
Published: October 2018

Purpose:

To investigate the levels of systemic heparanase, inflammatory markers, and coagulation factor activities in patients with retinal vein occlusion (RVO).

Methods:

This prospective study included 18 patients with central RVO, 22 patients with branch RVO, and 40 patients with age-related cataract as the control group. Serum heparanase protein levels and activities were measured by ELISA and a heparan degrading enzyme assay kit, respectively. Serum levels of MMP-2, MMP-9, TLR-2, and TLR-4 were measured by ELISA kits. The activities of coagulation factors (V, VII, VIII, and IX) were determined with an autoanalyzer. The Mann–Whitney U test was used to compare the above parameters between patients with RVO and control subjects. The relationship between two of the above parameters was analyzed by Spearman's correlation.

Results:

Patients with RVO had higher levels of systemic heparanase protein, heparanase activities, coagulation factors' (V, VIII, and IX) activities, MMP-2, MMP-9, TLR-2, and TLR-4 compared with the control group. Systemic heparanase levels were correlated with serum levels of MMP-2, MMP-9, TLR-2, TLR-4, and activities of coagulation factors VIII and IX.

Conclusion:

Increase of systemic heparanase in RVO is associated with activation of systemic inflammation and blood hypercoagulability.
Time for a Changing of Guard
Authors: Khan Muhammad Ali , Kahaleh Michel , Khan Zubair , Tyberg Amy , Solanki Shantanu , Haq Khwaja F. , Sofi Aijaz , Lee Wade M. , Ismail Mohammad K. , Tombazzi Claudio , Baron Todd H.
Published: October 2018

Background and Aims:

Endoscopic drainage (ED) with or without necrosectomy, and minimally invasive surgical necrosectomy (MISN) have been increasingly utilized for treatment of symptomatic sterile and infected pancreatic walled-off necrosis (WON). We conducted this systematic review to compare the safety of ED with MISN for management of WON.

Methods:

We searched several databases from inception through November 9, 2017 to identify comparative studies evaluating the safety of ED versus MISN for management of WON. MISN could be performed using video-assisted retroperitoneal debridement or laparoscopy. We evaluated difference in mortality, major organ failure, adverse events, and length of hospital stay.

Results:

Six studies (2 randomized controlled trials and 4 observational studies) with 641 patients (326 ED and 315 MISN) were included in this meta-analysis. Rates of mortality for ED and MISN were 8.5% and 14.2%, respectively. Pooled odds ratio (OR) with 95% confidence interval was 0.59 (0.35-0.98), I
2=0% in favor of ED. On subgroup analysis: no difference in mortality was seen based on randomized controlled trials [OR, 0.65 (0.08-5.11)], while ED had improved survival in observational studies [OR, 0.49 (0.27-0.89)]. Development of new major organ failure rates after interventions were 12% and 54% for ED and MISN, respectively. Pooled OR was 0.12 (0.06-0.31), I
2=25% in favor of ED. For adverse events, pooled OR was 0.25 (0.10-0.67), I
2=70% in favor of ED. There was no difference in risk of bleeding [OR, 0.68 (0.44-1.05)], while ED was associated with a significantly lower rate of pancreatic fistula formation [OR, 0.20 (0.11-0.37)], I
2=0%. Length of stay was also lower with ED, pooled mean difference was −21.07 (−36.97 to −5.18) days.

Conclusions:

When expertise is available, ED is the preferred invasive management strategy over MISN for management of WON as it is associated with lower mortality, risk of major organ failure, adverse events, and length of hospital stay.
Who are suitable for low-dose tamsulosin monotherapy as initial treatment strategy in male patients with lower urinary tract symptoms?
Authors: Kim Jae Heon , Shim Ji Sung , Choi Hoon , Park Jae Young , Kwon Soon-Sun , Bae Jae Hyun
Published: October 2018

This study aims to investigate the real indications for low-dose tamsulosin monotherapy for initial treatment.

A cross-sectional study was conducted in a total of 1643 patients with lower urinary tract symptoms (LUTS) and with initial low-dose tamsulosin. Initial pretreatment data including the International Prostate Symptoms Score (IPSS), prostate volume, and uroflowmetry data were reviewed. After 8 weeks of treatment, post-treatment IPSS and satisfaction was assessed. Logistic regression analysis was conducted to investigate the pretreatment factors influencing post-treatment satisfaction.

Overall satisfaction rate with low-dose tamsulosin as an initial treatment medication was 88.7%. Multivariate analysis revealed that symptom durations, IPSS voiding score, IPSS storage score, and quality of life (QoL) were determinant factors for patient satisfaction. ROC analysis revealed that a urinary score > 10 and symptom duration > 3 years showed satisfaction with a sensitivity of 85.8% and 90.6%, respectively, and specificity of 43.5% and 39.8%, respectively. Whereas, ROC analysis revealed that a storage score > 5 and QoL > 3 showed nonsatisfaction with sensitivity of 84.2% and 39.5%, respectively, and specificity of 43.5% and 45.7%, respectively. Multivariate regression analysis demonstrated that voiding score and storage score had a significant relationship with QoL (unstandardized coefficients: 0.073, 0.145, respectively; P-value: < .001, < .001, respectively).

The patient with higher storage scores and higher QoL before treatment could have a higher change of non-satisfaction. Combining treatment with anticholinergics could be considered in these patients.
The ratio of urinary sodium and potassium and chronic kidney disease progression
Authors: Koo Hoseok , Hwang Subin , Kim Tae Hee , Kang Sun Woo , Oh Kook-Hwan , Ahn Curie , Kim Yeong Hoon
Published: October 2018

The Na/K ratio in urine stands for the dietary of sodium and potassium intake in patients with chronic kidney disease remains unclear for the renal progression. We aimed to determine the risk of progression of chronic kidney disease based on the Na/K ratio in a 24-hour urine collection.

We determined the association between the progression of renal disease and 24-hour urinary sodium and potassium (Na/K) ratios in 2238 patients over a 5-year timespan using data obtained from the KoreaN cohort study for Outcomes in patients With Chronic Kidney Disease (KNOW-CKD). Renal events were defined as a 50% decrease in the glomerular filtration rate (GFR) below baseline, or the onset of end-stage renal disease (ESRD). Patients were divided into 4 groups based on the quartile range of the 24-hour urinary sodium and potassium ratio. We analyzed those variables in the 4 groups. Multiple logistic regression analyses were performed using the data of 1001 patients to identify the independent factors associated with renal events.

Age and male sex accounted for the greatest number of patients in the group with the highest values (group 4) of the 24-hour urinary Na/K ratio (≥3.85). There was no difference in the prevalence of hypertension or diabetes mellitus, the ratio of use of antihypertensive drugs, blood pressures, or estimated GFRs. In the group with the highest urinary Na/K ratio, the 24-hour urinary Na concentration mean ± standard deviation was 188.7 ± 70.6 mmol and that of urinary K was 39.9 ± 16.1 mmol. The urinary protein excretion was highest in the group with the highest urinary Na/K ratio. In the logistic regression analysis, the effect on renal events increased with increasing urinary Na/K ratios. After adjusting for other factors, the risk of renal events was 2.48 (95% confidence interval (CI) 1.30–4.90) in group 3, and 3.75 (95% CI: 1.35–11.27) in group 4. In the Kaplan–Meier analysis, the higher the urinary Na/K ratio, the higher the rate of CKD progression.

Based on our analyses, we concluded that the higher the urinary Na/K ratio, the greater the risk of CKD progression.
Sedentary behavior and the risk of cardiac-cerebral vascular diseases in southern China
Authors: Yu Lingling , Liang Qian , Zhou Wei , Huang Xiao , Hu Lihua , You Chunjiao , Li Juxiang , Wu Yanqing , Li Ping , Wu Qinghua , Bao Huihui , Cheng Xiaoshu
Published: October 2018

Accumulating evidence has reported that prolonged periods of sedentary time have been recognized as a risk factor for cardiocerebrovascular disease. However, whether high levels of sedentary behavior are associated with an increased risk of cardiocerebrovascular disease in different regions remains unclear.

The aim of this study was to evaluate the association between sedentary behavior and the risk of myocardial infarction (MI) and stroke in Jiangxi Province of China.

A cross-sectional survey was conducted among 15,364 participants in Jiangxi Province of China from November 2013 to August 2014, using standardized questionnaire forms and physical measurements. Self-reported sedentary behavior in daily life and a history of MI and stroke were conducted by answering the questionnaire. The participants were examined for weight, height, waist circumference (WC), body fat percentage (BFP), visceral fat index (VAI), basal metabolic rate (BMR), and blood pressure (BP). Multivariate logistic regression analysis was performed to evaluate the association between sedentary behavior and the risk of MI and stroke after adjustment for sociodemographic characteristics, lifestyle factors, and disease-related risk factors.

Of the 15,364 eligible participants, 13,710 participants (5604 men and 8106 women, aged 15–97 years) completed the questionnaire. Subjects who had longer sedentary behavior were significantly associated with an increased risk of MI and stroke [odds ratio (OR) = 1.22, 95% confidence interval (95% CI): 1.168–1.281, P < .001; OR = 1.59, 95% CI: 1.50–1.67, P < .001]. After stratification by the categorical variable of sedentary behavior, individuals with a longer time of sedentary behavior (≥8 hours) were also related to a higher risk of MI and stroke than those in the sedentary behavior (<4 hours) group (OR = 176.62, 95% CI: 43.33–719.90, P < .001; OR = 478.52, 95% CI: 118.50–1932.36, P < .001). However, there were no significant differences between individuals in the short time of sedentary behavior (<4 hours) group and the middle time (4–8 hours) group (p > 0.05).

Excessive time spent in sedentary behavior was associated with a higher risk of MI and stroke. The results provide robust evidence to support the guideline recommendations regarding reduction of sedentary behavior in daily life.
Laparoscopic pancreaticoduodenectomy for metastatic pancreatic melanoma
Authors: Liu Xueqing , Feng Feng , Wang Tianyang , Qin Jianzhang , Yin Xiangyan , Meng Guiqing , Yan Changqing , Xing Zhongqiang , Duan Jiayue , Liu Chen , Liu Jianhua
Published: October 2018

Rationale:

Pancreatic metastases from other malignant tumors are an uncommon clinical condition and account for approximately 2% of all pancreatic malignancies. The most common primary malignancy that metastasizes to pancreas is renal cell cancer. We reported a rare clinical case of metastatic melanoma to pancreas who underwent a successful laparoscopic pancreaticoduodenectomy (LPD) at our department.

Patient concerns:

A 54-year-old Chinese man complaining an unexplained jaundice was found to have a pancreatic mass and he was diagnosed with cutaneous melanoma (CM) 6 years ago.

Diagnoses:

Contrast-enhanced computed tomography (CECT) revealed a solid hypovascular mass measuring about 3.1 × 2.4 cm localized at the junction of pancreatic head and uncinate process, which compressed the lower common bile duct resulting in expansion of the upstream bile ducts.

Interventions:

We performed an LPD and regional lymphadenectomy on this patient.

Outcomes:

This patient was discharged home on postoperative day 19. Postoperative pathological results revealed a malignant melanoma with negative margins. Immunohistochemical (IHC) findings also suggested a malignant pancreatic tumor accompanied by necrosis and pigmentation, which confirmed the pathological diagnosis. Immunoreactivity was strongly positive for anti-S-100 protein (+++) and positive for anti-Vimentin (+). The cancer cells were negative for CEA, CK8/18, P53, Violin, CK19, SMA with Ki-67 over 40%. So this pancreatic mass was proved to be a metastatic pancreatic melanoma from the primary cutaneous lesion. After LPD, this patient was followed up by readmission to hospital every 2 month in the first half year. The serum bilirubin and tumor markers such as CA199 were normal. CECT and did not find any newly developed neoplasm at the pancreas or metastasis at other organs. At the last follow-up at 6 months after LPD, the patient's general condition was acceptable and the physical examination and imaging studies revealed no significant findings of melanoma.

Lessons:

Metastatic pancreatic tumors are often associated with well-defined margins, tumor necrosis, enhancement, and distant metastases without pancreatic duct dilatation and parenchymal atrophy. As the most common type of metastatic pancreatic tumor, renal cell cancers tend to have higher attenuation values than that of primary pancreatic cancer, while they had similar attenuation values on the portal phase. Primary pancreatic cancer was always associated with an elevated CA199, total bilirubin, and fasting plasma glucose levels. Surgical resection for metastases to pancreas should be aggressively considered in selected patients due to its unique value of providing palliation and a chance to cure. For patients with unresectable lesions, new therapeutic protocols should be recommended such as the combination of BRAF with MEK inhibitor and PD-1 blocker with or without ipilimumab.
Intraoperative cholangiography versus magnetic resonance cholangiography in patients with mild acute biliary pancreatitis
Authors: Gómez-Torres Gustavo Angel , González-Hernández Jaime , López-Lizárraga Carlos Rene , Navarro-Muñiz Eliseo , Ortega-García Odeth Sherlyne , Bonnet-Lemus Francisco Manuel , Abarca-Rendon Francisco Manuel , De la Cerda-Trujillo Liliana Faviola
Published: October 2018

Cholecystectomy is the only definitive management of pancreatitis secondary to gallstone disease. Approximately 20% to 30% of patients with acute biliary pancreatitis (ABP) will have persistent common bile duct (CBD) stones. Therefore, choosing a method for the early diagnosis of choledocholithiasis is essential to reduce waiting days for surgery and hospital stay in these patients.

The aim of this study was to compare the use of magnetic resonance cholangiography (MRC) and intraoperative cholangiography (IOC), and its impact on the length of the hospital stay in patients with mild ABP and an intermediate probability of choledocholithiasis.

We prospectively evaluated all patients diagnosed with mild ABP and an intermediate probability of choledocholithiasis at admission and 48 hours after, from June, 2017 to December, 2017. Study subjects were identified upon admission and were classified into 2 groups of patients according to their choledocholithiasis predictors; a MRC was performed in the group 1, and an IOC was done in group 2.

In all, 47 patients were enrolled in the final analysis of this study. Hospital stay in group 1 (CMR) patients was 8.29 (±2.69) days compared with 6.43 (±2.57) days in the group 2 (IOC) (P = .007). Mean waiting days for cholecystectomy was 17.14 (±26.04) days for group 1 and 5 (±2.69) days for group 2.

We suggest an IOC as the election method for the diagnosis of CBD stones in patients with mild ABP in medical centers similar to ours because it reduces waiting days for surgery and hospital stay compared to the MRC.