bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence-based practice and patient-centered care: Doing both well
Authors: Engle Ryann L. , Mohr David C. , Holmes Sally K. , Seibert Marjorie Nealon , Afable Melissa , Leyson Jenniffer , Meterko Mark 
Published: June 2019

Background
Health care organizations increasingly strive to deliver care that is both evidence based and patient centered. Although often complementary, fundamental contradictions may exist between these goals, and the organizational culture and infrastructure necessary to be successful in one domain may inherently diminish performance in the other.

Purpose
We assessed the relationship between evidence-based practice (EBP) and patient-centered care (PCC) by seeking to identify specific behavioral and process mechanisms, along with organizational characteristics that distinguish medical centers that are able to provide inpatient care that is both evidence based and patient centered from those where performance is either mixed or low in both domains.

Methodology/Approach
We analyzed interview data from 142 employees at 12 Veterans Affairs Medical Centers selected based on EBP and PCC performance (high, low, or mixed) using a priori constructs consistent with organizational literature, as well as emergent themes.

Results
We confirmed that tensions may arise when attempting to deliver both EBP and PCC and found unique characteristics of organizations that do both well. High-performing sites exhibited organizational cultures of empowerment where both EBP and PCC expectations were emphasized; provided formal and informal institutional supports and structures with regard to PCC and EBP; and fostered multidisciplinary, multidirectional approaches to care and communication that facilitated delivery of both EBP and PCC.

Conclusions and Practice Implications
Organizations that excel in providing both EBP and PCC exhibit unique characteristics and processes. Recognizing that some characteristics such as culture are difficult to change, these findings nonetheless highlight areas that could be enhanced by medical centers striving to deliver care that is both evidence based and patient centered.
Long-term Results of Trabeculectomy With Mitomycin-C in Patients With Bilateral Acute Iris Transillumination
Authors: Bayraktar Serife , Oray Merih , Altan Cigdem , Basarir Berna , Izgi Belgin , Tugal-Tutkun Ilknur 
Published: June 2019

Précis:
The present study suggests that immediate trabeculectomy with mitomycin C (MMC) may be performed as a safe and effective intervention in the management of refractory ocular hypertension (OHT)/glaucoma in patients with bilateral acute iris transillumination (BAIT).

Purpose:
To report the long-term results of trabeculectomy with MMC in the management of OHT/glaucoma in patients with BAIT.

Materials and Methods:
In total, 9 eyes of 6 patients with BAIT who underwent trabeculectomy with MMC between 2007 and 2015 were reviewed. Main outcome measures were control of intraocular pressure (IOP), the number of antiglaucomatous medications required to achieve the desired IOP, and complications.

Results:
The postoperative follow-up time ranged between 2 and 9.5 years. IOP at presentation was >21 mm Hg in all patients. Maximum IOP with maximum antiglaucomatous medications during follow-up before surgery ranged between 36 and 55 mm Hg. At last visit, IOP ranged between 8 and 17 mm Hg, and 6 of 9 of the eyes required no antiglaucomatous medications. There was no failure in any patients according to the guidelines of the World Glaucoma Association. The most common complication was cataract formation in 7 eyes.

Conclusions:
The favorable outcomes observed during 2 to almost 10 years following surgical intervention are encouraging. Therefore, trabeculectomy with MMC provides long-term safe and effective results in OHT/glaucoma in patients with BAIT.
Outcome of Children Treated for Infantile Hepatic Hemangioendothelioma
Authors: Emad Ahmed , Fadel Sayed , El wakeel Madeeha , Nagy Nouran , Zamzam Manal , Kieran Mark W. , El Haddad Alaa 
Published: June 2019

Purpose:
Infantile hepatic hemangioendothelioma (IHHE) is the most common hepatic vascular tumor in children. We report on the treatment outcome of our large single-center experience of patients with IHHE over a 9-year period.

Materials and Methods:
A retrospective analysis of all IHHE patients treated at the Children Cancer Hospital Egypt from April 2008 through April 2017.

Results:
In total, 28 patients (18 females, 10 males) were diagnosed with IHHE with a median age at diagnosis of 3 months. The lesions were multifocal (n=12), focal (n=10), and diffuse (n=6). Six (21.4%) patients initially had low T3 and T4. Eleven patients did not receive any treatment, whereas 1 patient underwent resectional surgery. Sixteen patients received drug treatment, 9 of whom responded well to first-line propranolol/prednisolone, whereas 7 patients needed salvage treatment. Twenty-five patients are alive, whereas 3 patients have died.

Conclusions:
Overall, patients with IHHE do well, a significant percentage of whom do not require drug therapy, particularly for those with small focal lesions. In patients with multifocal/diffuse disease, there is a high incidence of low T3 and T4 and while some of these patients did well without additional therapy, those with rapidly progressive lesions during treatment may do poorly.
How Should Pancreas Transplant Rejection Be Treated?
Authors: Aziz Fahad , Parajuli Sandesh , Uddin Salah , Harrold Kylie , Djamali Arjang , Astor Brad , Odorico Jon , Mandelbrot Didier 
Published: June 2019

Background.
Limited published data exist to guide the treatment of pancreas transplant rejection.

Methods.
We reviewed the treatment and outcomes of 158 first episodes of biopsy-proven pancreas rejection between 1 January 1997 and 31 December 2016. Within each Banff grade of rejection, we compared response rates and long-term outcomes with steroids alone versus steroids plus antithymocyte globulin (ATG).

Results.
Of 158 pancreas recipients with rejection, 65 were treated with steroids alone. Eighty-three percent of patients with grade I, 60% with grade II, and 33.33% with grade III rejection responded to treatment with steroids alone. Ninety-three patients were treated with steroids plus ATG. The response rates were 69% in grade I, 76% in grade II, and 73% in grade III. Response rates and graft survival were not different with grade I rejection treated with steroids alone versus steroids plus ATG. However, response rates and graft survival were significantly better with grade III rejection treated with the addition of ATG, and graft survival rates were significantly better with grade II rejection treated with the addition of ATG.

Conclusions.
Grade I pancreas rejection can usually be successfully treated with steroids alone, whereas grade II and III rejection should usually be treated with steroids plus ATG, as the addition of ATG improves both response rates and graft survival.
Maximizing viral detection with SIV droplet digital PCR (ddPCR) assays
Authors: Long Samuel , Berkemeire Brian 
Published: June 2019

AbstractHighly sensitive detection of HIV-1 nucleic acids is of critical importance for evaluating treatment interventions superimposed on combination antiretroviral therapy (cART) in HIV-1 infected individuals. SIV infection of rhesus macaques models many key aspects of human HIV-1 infection and plays a key role in evaluation of approaches for prevention, treatment and attempted eradication of HIV infection. Here we describe ultrasensitive droplet digital PCR (ddPCR) DNA and RT-ddPCR RNA assays for detecting simian immunodeficiency virus (SIV) on the Raindance ddPCR platform. We demonstrate that RainDance ddPCR can tolerate significantly higher cell DNA input without inhibition on a per reaction basis, exceeding the Bio-Rad ddPCR per-reaction input limit by about 18-fold, effectively increasing viral detection sensitivity by allowing a large quantity of sample to be analyzed in each reaction. In addition, the combination of a high processivity RT enzyme and RainDance ddPCR could overcome inhibition in severely inhibited viral RNA samples. These assays offer valuable tools for assessing low level viral production/replication and strategies for targeting residual virus in the setting of cART suppression of viral replication. The methodologies presented here can be adapted for a broad range of applications where highly sensitive nucleic acid detection is required.
Changes in the intracranial volume from early adulthood to the sixth decade of life: A longitudinal study
Authors: Caspi Yaron , Brouwer Rachel M. , Schnack Hugo G. , van de Nieuwenhuijzen Marieke E. , Cahn Wiepke , Kahn René S. , Niessen Wiro J. , van der Lugt Aad , Pol Hilleke Hulshoff 
Published: June 2019

AbstractNormal brain-aging occurs at all structural levels. Excessive pathophysiological changes in the brain, beyond the normal one, are implicated in the etiology of brain disorders such as severe forms of the schizophrenia spectrum and dementia. To account for brain-aging in health and disease, it is critical to study the age-dependent trajectories of brain biomarkers at various levels and among different age groups.The intracranial volume (ICV) is a key biological marker, and changes in the ICV during the lifespan can teach us about the biology of development, aging, and gene X environment interactions. However, whether ICV changes with age in adulthood is not resolved.Applying a semi-automatic in-house-built algorithm for ICV extraction on T1w MR brain scans in the Dutch longitudinal cohort (GROUP), we measured ICV changes. Individuals between the ages of 16 and 55 years were scanned up to three consecutive times with 3.32±0.32 years between consecutive scans (N=482, 359, 302). Using the extracted ICVs, we calculated ICV longitudinal aging-trajectories based on three analysis methods; direct calculation of ICV differences between the first and the last scan, fitting all ICV measurements of individuals to a straight line and applying a global linear mixed model fitting. We report statistically significant increases in the ICV in adulthood until the fourth decade of life (average change +0.03%/y, or about 0.5 ml/y, at age 20), and decreases in the ICV afterward (−0.09%/y, or about −1.2 ml/y, at age 55). To account for previous cross-sectional reports of ICV changes, we analyzed the same data using a cross-sectional approach. Our cross-sectional analysis detected ICV changes consistent with the previously reported cross-sectional effect. However, the reported amount of cross-sectional changes within this age range was significantly larger than the longitudinal changes. We attribute the cross-sectional results to a generational effect.In conclusion, the human intracranial volume does not stay constant during adulthood but instead shows a small increase during young adulthood and a decrease thereafter from the fourth decade of life. The age-related changes in the longitudinal setup are smaller than those reported using cross-sectional approaches and unlikely to affect structural brain imaging studies correcting for intracranial volume considerably. As to the possible mechanisms involved, this awaits further study, although thickening of the meninges and skull bones have been proposed, as well as a smaller amount of brain fluids addition above the overall loss of brain tissue.
Classification of human white blood cells using machine learning for stain-free imaging flow cytometry
Authors: Lippeveld Maxim , Knill Carly , Ladlow Emma , Fuller Andrew , Michaelis Louise J , Saeys Yvan , Filby Andrew , Peralta Daniel 
Published: June 2019

AbstractImaging flow cytometry (IFC) produces up to 12 different information-rich images of single cells at a throughput of 5000 cells per second. Yet often, cell populations are still studied using manual gating, a technique that has several drawbacks. Firstly, it is hard to reproduce. Secondly, it is subjective and biased. And thirdly, it is time-consuming for large experiments. Therefore, it would be advantageous to replace manual gating with an automated process, which could be based on stain-free measurements originating from the brightfield and darkfield image channels. To realise this potential, advanced data analysis methods are required, in particular, machine learning. Previous works have successfully tested this approach on cell cycle phase classification with both a classical machine learning approach based on manually engineered features, and a deep learning approach. In this work, we compare both approaches extensively on the complex problem of white blood cell classification. Four human whole blood samples were assayed on an ImageStream-X MK II imaging flow cytometer. Two samples were stained for the identification of 8 white blood cell types, while two other sample sets were stained for the identification of resting and active eosinophils. For both datasets, four machine learning classifiers were evaluated on stain-free imagery using stratified 5-fold cross-validation. On the white blood cell dataset the best obtained results were 0.776 and 0.697 balanced accuracy for classical machine learning and deep learning, respectively. On the eosinophil dataset this was 0.866 and 0.867 balanced accuracy. From the experiments we conclude that classifying distinct cell types based on only stain-free images is possible with these techniques. However, both approaches did not always succeed in making reliable cell subtype classifications. Also, depending on the cell type, we find that even though the deep learning approach requires less expert input, it performs on par with a classical approach.
Multidimensional phenotyping predicts lifespan and quantifies health inC. elegans
Authors: Martineau Céline N. , Brown André E. X. , Laurent Patrick 
Published: June 2019

AbstractAgeing affects a wide range of phenotypes at all scales, but an objective measure of ageing remains challenging, even in simple model organisms. We assumed that a wide range of phenotypes at the organismal scale rather than a limited number of biomarkers of ageing would best describe the ageing process. Hundreds of morphological, postural and behavioural features are extracted at once from high resolutions videos. A quantitative model using this multi-parametric dataset can predict the biological age and lifespan of individualC. elegans. We show that the quality of predictions on a held-out data set increases with the number of features added to the model, supporting our initial hypothesis. Despite the large diversity of ageing mechanisms, including stochastic insults, our results highlight a robust ageing trajectory, but variable ageing rates along that trajectory. We show that healthspan, which we defined as the range of abilities of the animals, is correlated to lifespan in wild-type worms.
The genome design suite: enabling massive in-silico experiments to design genomes
Authors: Chalkley Oliver , Purcell Oliver , Grierson Claire , Marucci Lucia 
Published: June 2019

AbstractMotivationComputational biology is a rapidly developing field, and in-silico methods are being developed to aid the design of genomes to create cells with optimised phenotypes. Two barriers to progress are that in-silico methods are often only developed on a particular implementation of a specific model (e.g. COBRA metabolic models) and models with longer simulation time inhibit the large-scale in-silico experiments required to search the vast solution space of genome combinations.ResultsHere we present the genome design suite (PyGDS) which is a suite of Python tools to aid the development of in-silico genome design methods. PyGDS provides a framework with which to implement phenotype optimisation algorithms on computational models across computer clusters. The framework is abstract allowing it to be adapted to utilise different computer clusters, optimisation algorithms, or design goals. It implements an abstract multi-generation algorithm structure allowing algorithms to avoid maximum simulation times on clusters and enabling iterative learning in the algorithm. The initial case study will be genome reduction algorithms on a whole-cell model of Mycoplasma genitalium for a PBS/Torque cluster and a Slurm cluster.AvailabilityThe genome design suite is written in Python for Linux operating systems and is available from GitHub on a GPL open-source licence.Contacto.chalkley@bristol.ac.uk, lacsg@bristol.ac.uk, and lucia.marucci@bristol.ac.uk.
Real time health monitoring through urine metabolomics
Authors: Miller Ian , Peters Sean R. , Overmyer Katherine A. , Paulson Brett R. , Westphall Michael S. , Coon Joshua J. 
Published: June 2019

AbstractCurrent healthcare practices are reactive and based on limited physiological information collected months or years apart. By enabling patients and healthy consumers access to continuous measurements of health, wearable devices and digital medicine stand to realize highly personalized and preventative care. However, most current digital technologies provide information on a limited set of physiological traits, such as heart rate and step count, which alone offer little insight into the etiology of most diseases. Here we propose to integrate data from biohealth smartphone applications with continuous metabolic phenotypes derived from urine metabolites. This combination of molecular phenotypes with quantitative measurements of lifestyle reflect the biological consequences of human behavior in real time. We present data from an observational study involving two healthy subjects and discuss the challenges, opportunities, and implications of integrating this new layer of physiological information into digital medicine. Though our dataset is limited to two subjects, our analysis (also available through an interactiveweb-based visualization tool) provides an initial framework to monitor lifestyle factors, such as nutrition, drug metabolism, exercise, and sleep using urine metabolites.
Decoding and perturbing decision states in real time
Authors: Peixoto Diogo , Verhein Jessica R. , Kiani Roozbeh , Kao Jonathan C. , Nuyujukian Paul , Chandrasekaran Chandramouli , Brown Julian , Fong Sania , Ryu Stephen I. , Shenoy Krishna V. , Newsome William T. 
Published: June 2019

SummaryIn dynamic environments, subjects often integrate multiple samples of a signal and combine them to reach a categorical judgment. The process of deliberation on the evidence can be described by a time-varying decision variable (DV), decoded from neural activity, that predicts a subject’s decision at the end of a trial. However, within trials, large moment-to-moment fluctuations of the DV are observed. The behavioral significance of these fluctuations and their role in the decision process remain unclear. Here we show that within-trial DV fluctuations decoded in real time from motor cortex are tightly linked to choice behavior, and that robust changes in DV sign have the statistical regularities expected from behavioral studies of changes-of-mind. Furthermore, we find single-trial evidence for absorbing decision bounds. As the DV builds up, heavily favoring one or the other choice, moment-to-moment variability in the DV is reduced, and both neural DV and behavioral decisions become resistant to additional pulses of sensory evidence as predicted by diffusion-to-bound and attractor models of the decision process.
Conformational dynamics of FERM-mediated autoinhibition in Pyk2 tyrosine kinase
Authors: Loving Hanna S. , Underbakke Eric S. 
Published: June 2019

AbstractPyk2 is a non-receptor tyrosine kinase that evolved from gene duplication of focal adhesion kinase (FAK) and subsequent functional specialization in the brain and hemopoietic cells. Pyk2 shares a domain organization with FAK, with an N-terminal regulatory FERM domain adjoining the kinase domain. FAK regulation involves integrin-mediated membrane clustering to relieve autoinhibitory interactions between FERM and kinase domains. Pyk2 regulation remains cryptic, involving Ca2+ influx and protein scaffolding. While the mechanism of the FAK FERM domain in autoinhibition is well-established, the regulatory role of the Pyk2 FERM is ambiguous. We probed the mechanisms of FERM-mediated autoinhibition of Pyk2 using hydrogen/deuterium exchange mass spectrometry (HDX-MS) and kinase activity profiling. The results reveal FERM-kinase interfaces responsible for autoinhibition. Pyk2 autoinhibition impacts activation loop conformation. In addition, the autoinhibitory FERM-kinase interface exhibits allosteric linkage with the FERM basic patch conserved in both FAK and Pyk2.Table of Contents graphic
Psychiatric assessment in congenital blindness, ASD and ID: experience from two clinical cases
Authors: Kildahl Arvid Nikolai , Engebretsen Maria Hagen , Horndalsveen Kristin , Hellerud Jane Margrete Askeland , Wiik Jorunn Ytrehorn , Aasen Gro , Helverschou Sissel Berge 
Published: June 2019

PurposePsychiatric assessment in adults with autism spectrum disorder (ASD) and intellectual disability (ID) is complex and challenging. With co-occurring congenital blindness, this complexity is increased. Systematic knowledge about psychiatric assessment in this combination of challenges is virtually non-existing, and there is little guidance available for clinicians faced with this task. The paper aims to discuss these issues.Design/methodology/approachExperiences from comprehensive psychiatric assessments in two adults with congenital blindness, ASD, and ID are explored and discussed.FindingsAdaptation of assessment procedures usually employed for individuals with ASD and ID involved no major alteration, but co-operation between mental health and visual impairment professionals was important, as was the involvement of the families of the individuals in question. In both cases, the patient met criteria for an anxiety disorder, underlining the vulnerability and the challenges involved in living with this combination of challenges.Research limitations/implicationsThere is an urgent need for research into mental health issues for this group, including case studies describing successful treatment or intervention for these issues.Practical implicationsPsychiatric assessment in individuals with this combination of challenges may be feasible, but requires involvement of professionals specializing in mental health in developmental disabilities, and professionals in visual impairment. Assessments need to be individually adapted.Originality/valueThis is the first study systematically describing psychiatric assessment in this group involving the use of checklists and assessment tools. Strategies and tools that were useful are described and discussed to aid other clinicians faced with similar challenges.