bluuebunny/crossref_metadata_2025 huggingface dataset:
An evolutionary model motivated by physicochemical properties of amino acids reveals variation among proteins
Authors: Braun Edward L
Published: April 2018

Motivation

The relative rates of amino acid interchanges over evolutionary time are likely to vary among proteins. Variation in those rates has the potential to reveal information about constraints on proteins. However, the most straightforward model that could be used to estimate relative rates of amino acid substitution is parameter-rich and it is therefore impractical to use for this purpose.

Results

A six-parameter model of amino acid substitution that incorporates information about the physicochemical properties of amino acids was developed. It showed that amino acid side chain volume, polarity and aromaticity have major impacts on protein evolution. It also revealed variation among proteins in the relative importance of those properties. The same general approach can be used to improve the fit of empirical models such as the commonly used PAM and LG models.

Availability and implementation

Perl code and test data are available from https://github.com/ebraun68/sixparam.

Supplementary information

Supplementary data are available at Bioinformatics online.
An integration of fast alignment and maximum-likelihood methods for electron subtomogram averaging and classification
Authors: Zhao Yixiu , Zeng Xiangrui , Guo Qiang , Xu Min
Published: April 2018

Motivation

Cellular Electron CryoTomography (CECT) is an emerging 3D imaging technique that visualizes subcellular organization of single cells at sub-molecular resolution and in near-native state. CECT captures large numbers of macromolecular complexes of highly diverse structures and abundances. However, the structural complexity and imaging limits complicate the systematic de novo structural recovery and recognition of these macromolecular complexes. Efficient and accurate reference-free subtomogram averaging and classification represent the most critical tasks for such analysis. Existing subtomogram alignment based methods are prone to the missing wedge effects and low signal-to-noise ratio (SNR). Moreover, existing maximum-likelihood based methods rely on integration operations, which are in principle computationally infeasible for accurate calculation.

Results

Built on existing works, we propose an integrated method, Fast Alignment Maximum Likelihood method (FAML), which uses fast subtomogram alignment to sample sub-optimal rigid transformations. The transformations are then used to approximate integrals for maximum-likelihood update of subtomogram averages through expectation–maximization algorithm. Our tests on simulated and experimental subtomograms showed that, compared to our previously developed fast alignment method (FA), FAML is significantly more robust to noise and missing wedge effects with moderate increases of computation cost. Besides, FAML performs well with significantly fewer input subtomograms when the FA method fails. Therefore, FAML can serve as a key component for improved construction of initial structural models from macromolecules captured by CECT.

Availability and implementation

http://www.cs.cmu.edu/mxu1
PrimAlign: PageRank-inspired Markovian alignment for large biological networks
Authors: Kalecky Karel , Cho Young-Rae
Published: April 2018

Motivation

Cross-species analysis of large-scale protein–protein interaction (PPI) networks has played a significant role in understanding the principles deriving evolution of cellular organizations and functions. Recently, network alignment algorithms have been proposed to predict conserved interactions and functions of proteins. These approaches are based on the notion that orthologous proteins across species are sequentially similar and that topology of PPIs between orthologs is often conserved. However, high accuracy and scalability of network alignment are still a challenge.

Results

We propose a novel pairwise global network alignment algorithm, called PrimAlign, which is modeled as a Markov chain and iteratively transited until convergence. The proposed algorithm also incorporates the principles of PageRank. This approach is evaluated on tasks with human, yeast and fruit fly PPI networks. The experimental results demonstrate that PrimAlign outperforms several prevalent methods with statistically significant differences in multiple evaluation measures. PrimAlign, which is multi-platform, achieves superior performance in runtime with its linear asymptotic time complexity. Further evaluation is done with synthetic networks and results suggest that popular topological measures do not reflect real precision of alignments.

Availability and implementation

The source code is available at http://web.ecs.baylor.edu/faculty/cho/PrimAlign.

Supplementary information

Supplementary data are available at Bioinformatics online.
Antimicrobial Stewardship Training for Infectious Diseases Fellows: Program Directors Identify a Curriculum Need
Authors: Luther Vera P , Shnekendorf Rachel , Abbo Lilian M , Advani Sonali , Armstrong Wendy S , Barsoumian Alice E , Beeler Cole B , Bystritsky Rachel , Cherabuddi Kartikeya , Cohen Seth , Hamilton Keith W , Ince Dilek , Justo Julie Ann , Logan Ashleigh , Lynch John B , Nori Priya , Ohl Christopher A , Patel Payal K , Pottinger Paul S , Schwartz Brian S , Stack Conor , Zhou Yuan
Published: April 2018

A needs assessment survey of infectious diseases (ID) training program directors identified gaps in educational resources for training and evaluating ID fellows in antimicrobial stewardship. An Infectious Diseases Society of America–sponsored core curriculum was developed to address that need.
Daily Stress Reactivity Across the Life span: Longitudinal and Cross-Sectional Effects of Age
Authors: Blaxton Jessica , Bergeman C S , Wang Lijuan
Published: April 2018

Objective

Exploration of development requires the use of research designs and process-oriented methodologies that can capture daily fluctuations within individuals, systematic changes within individuals, and differences between individuals. We examine the stress–affect relationship in this way to assess how the relationship between daily stress and negative affect (NA) as well as the relationship between daily stress and positive affect (PA) differs between individuals and changes over time depending on age and stress differences.

Method

Participants (N = 966) completed daily “burst” assessments of stress, NA, and PA. Three-level multilevel models depicted how cross-sectional age, within-person age changes, and global stress differences impact the daily stress–affect relationship.

Results

Findings illustrate that cross-sectional age and the aging process uniquely buffer the stress–NA relationship whereas global stress exacerbates it. Furthermore, older adults as well as adults with low global stress experience a weaker relationship between daily stress and PA as they age, but midlife adults and adults with high global stress experience a stronger relationship.

Discussion

These results depict differences in aging trajectories for both midlife and older adults and thus inform intervention and preventative care strategies aimed toward promoting stress regulation.
Validity and Reliability of the Major Depression Inventory for Persons With Dual Sensory Loss
Authors: Hovaldt Hanna Birkbak , Nielsen Tine , Dammeyer Jesper
Published: April 2018

Background and Objectives

Research has shown that dual sensory loss is a risk factor for depression in older adults. However, validated measures of depression for people with dual sensory loss are lacking. The purpose of the present study was to investigate the construct validity and reliability of the Major Depression Inventory for use among elderly persons with acquired dual sensory loss.

Research Design and Methods

A cross-sectional questionnaire survey was conducted in a national sample of people ≥50 years of age with functional acquired dual sensory loss. Of the invited participants, 302 (66%) returned the questionnaire and 207 complete cases were included for analysis. Rasch models and graphical log-linear Rasch models were used for item analysis. Lack of differential item functioning was tested relative to severity of vision and hearing impairment, mode of questionnaire completion, age, sex, comorbidity, instrumental activities of daily living, social position, and cohabitation status.

Results

The 10-item Major Depression Inventory did not fit the Rasch model. An 8-item version, excluding the items “feeling sad” and “sleep problems,” fit a graphical log-linear Rasch model. No evidence of differential item functioning was discovered, thus the 8-item Major Depression Inventory was measurement invariant across severity of impairments and mode of completing the questionnaire. The overall reliability was 0.81 and ranged from acceptable to good for all subgroups of participants, except males with severe hearing impairment and low functional status. Consequently, the 8-item version of the Major Depression Inventory was considered construct valid and reliable within the frame of reference.

Discussion and Implications

An 8-item version of the Major Depression Inventory can be used to screen for depressive symptoms in elderly persons with acquired dual sensory loss.
The 2017 August 21 American total solar eclipse through the eyes of GPS
Authors: Kundu Bhaskar , Panda Dibyashakti , Gahalaut Vineet K , Catherine J K
Published: April 2018

We explored spatio-temporal variation in total electron contents (TEC) in the ionosphere caused by the recent 2017 August 21 total solar eclipse, which was observed over the United States of America. The path of the total solar eclipse passes through the continental parts of the United States of America, starting in the northwestern state of Oregon and ending in the southeastern state of South Carolina, approximately covering 4000 km length. Across this length, EarthScope Plate Boundary Observatory (PBO) has been operating a dense Global Navigation Satellite Systems (GNSS) networks. During the course of passage of the solar eclipse, the sudden decline in solar radiation by temporarily obscuration by the Moon caused a drop of ∼6–9 × 1016 electrons m2 in the ionosphere with time-delay at the cGPS sites. The significant drop in TEC at cGPS sites captured the average migration velocity of shadow along the eclipse path (0.74 km s−1), from which we estimated the Moon's orbital velocity (∼1 km s−1). Further, this event also caused some marginal increase in TEC during the eclipse in the Earth's ionosphere in the magnetically conjugate region at the tip of South America and Antarctica, consistent with the model predictions of SAMI3 by Naval Research Laboratory.
Impacts of temperature and food availability on the condition of larval Arctic cod (Boreogadus saida) and walleye pollock (Gadus chalcogrammus)
Authors: Koenker Brittany L , Copeman Louise A , Laurel Benjamin J
Published: April 2018

The Arctic marine environment is rapidly changing with rising sea surface temperatures, declining sea ice habitat and projected increases in boreal species invasions. The success of resident Arctic fish will depend on both their thermal tolerance and their ability to cope with changing trophic interactions. Larval fish energetic condition is closely associated with mortality rates and therefore provides an indicator of overall well-being or fitness. In this study, we experimentally determined larval morphometric and lipid-based condition in an Arctic gadid (Arctic cod, Boreogadus saida) and a boreal gadid (walleye pollock, Gadus chalcogrammus) in response to different temperatures and food rations. Our results suggest that larval condition is highly sensitive to both factors but varies in a species- and ontogenetic-dependent manner. Results indicated that condition metrics based on length–weight relationships were not as sensitive as those based on lipid storage. Further, condition metrics changed with ontogeny and were best used within a developmental stage rather than across developmental stages. As expected, larval condition in first-feeding Arctic cod was higher at colder temperatures (2–5°C) than in the boreal gadid (5–12°C). However, at more developed larval stages the peak condition for Arctic cod was at warmer temperatures (7°C), while walleye pollock had the same thermal optimum as during earlier stages. Arctic cod were more sensitive to food ration at first feeding than walleye pollock, however; at later larval stages both species had a negative condition response to low food ration, especially at elevated temperatures (5 vs. 7°C). The lower thermal tolerance of Arctic cod, coupled with a higher sensitivity to food availability indicates that Arctic cod are particularly vulnerable to on-going environmental change. Arctic cod is a lipid-rich keystone species and therefore a reduction in their energetic condition during summer has the potential to affect the health of higher trophic levels throughout the Alaskan Arctic.
An inexact regularized Newton framework with a worst-case iteration complexity of $ {\mathscr O}(\varepsilon^{-3/2}) $ for nonconvex optimization
Authors: Curtis Frank E , Robinson Daniel P , Samadi Mohammadreza
Published: April 2018

An algorithm for solving smooth nonconvex optimization problems is proposed that, in the worst-case, takes ${\mathscr O}(\varepsilon ^{-3/2})$ iterations to drive the norm of the gradient of the objective function below a prescribed positive real number $\varepsilon $ and can take ${\mathscr O}(\varepsilon ^{-3})$ iterations to drive the leftmost eigenvalue of the Hessian of the objective above $-\varepsilon $. The proposed algorithm is a general framework that covers a wide range of techniques including quadratically and cubically regularized Newton methods, such as the Adaptive Regularization using Cubics (arc) method and the recently proposed Trust-Region Algorithm with Contractions and Expansions (trace). The generality of our method is achieved through the introduction of generic conditions that each trial step is required to satisfy, which in particular allows for inexact regularized Newton steps to be used. These conditions center around a new subproblem that can be approximately solved to obtain trial steps that satisfy the conditions. A new instance of the framework, distinct from arc and trace, is described that may be viewed as a hybrid between quadratically and cubically regularized Newton methods. Numerical results demonstrate that our hybrid algorithm outperforms a cubically regularized Newton method.
Venous Thromboembolism After Intraventricular Hemorrhage: Results From the CLEAR III Trial
Authors:   CLEAR III Trial Investigators, Shah Jharna N , Murthy Santosh B , Dlugash Rachel , McBee Nichol , Awad Issam , Hanley Daniel F , Ziai Wendy C
Published: April 2018

BACKGROUND

Venous thromboembolism (VTE) after intracerebral hemorrhage is well studied, but data on patients with spontaneous intraventricular hemorrhage (IVH) are limited.

OBJECTIVE

To study the factors associated with VTE, association between VTE and clinical outcomes in IVH, and safety of VTE chemoprophylaxis in IVH treated with intraventricular catheters and thrombolysis.

METHODS

Retrospective cohort study of patients enrolled in the CLEAR III trial, a multicenter, randomized trial comparing external ventricular drainage, with administration of intraventricular alteplase vs placebo, for obstructive IVH. Predictor variable was incident VTE in the first 30 d. Outcome measures were factors associated with VTE, and death/severe disability (modified Rankin Score 4-6) at 6 mo.

RESULTS

Of the 500 patients with IVH, VTE occurred in 59 patients (11.8%) within the first 30 d. VTE chemoprophylaxis was initiated in 412 (82.4%) patients, but before VTE diagnosis in only 401 (80.2%) at median of 4 d (interquartile range, 1-8) from IVH onset, and was not associated with intracranial bleeding or catheter tract hemorrhage. In the multivariate logistic regression analysis, infection within 30 d (odds ratio, 1.80; confidence interval, 1.03-3.17) was significantly associated with higher odds of VTE occurrence. Starting VTE chemoprophylaxis after 72 h was additionally associated with VTE occurrence after the first week.

CONCLUSION

Infection and delay in timely initiation of VTE chemoprophylaxis were associated with VTE occurrence. VTE chemoprophylaxis in IVH appears safe and should not be delayed beyond standard care policies for ICH including when intraventricular catheter placement and thrombolytic therapy are performed.
Association of Smokeless Tobacco Use and Oral Cancer: A Systematic Global Review and Meta-Analysis
Authors: Asthana Smita , Labani Satyanarayana , Kailash Uma , Sinha Dhirendra N , Mehrotra Ravi
Published: April 2018

Introduction

Smokeless tobacco products have been linked to precancerous and cancers of oral cavity for long. Evidence was available on the association between smokeless tobacco (SLT) products and oral cancers at regional but not at global level. Present meta-analysis is aimed to evaluate the risk of oral cancer with the use of SLT products among “ever” versus “never” users.

Method

Studies published for the period (1960–2016) are retrieved using Pubmed, Indmed, EMBASE, and Google Scholar search engines for the subject “ever” versus “never” users of SLT products and estimated the risk association with oral cancer. Summary odds ratios (relative risk) are estimated and meta-analysis was performed using random-effects model.

Results

Thirty-seven studies from four of six WHO regions, Southeast Asia region (SEAR), the Eastern Mediterranean Region (EMR), Europe, and region of Americas (North and South) are included in the analysis. Significant risk with SLT products with oral cancer was found for SEAR (4.44, 95% CI = 3.51 to 5.61) and for EMR (1.28, 95% CI = 1.04 to 1.56). Significantly higher risk (p < .001) was found for females (5.83, 95% CI = 2.93 to 11.58). Product wise analysis for different SLT products revealed various levels of risk viz. gutkha (8.67, 95% CI = 3.59 to 20.93), pan tobacco / betel liquid (7.18, 95% CI = 5.48 to 9.41), oral snuff (4.18, 50% CI = 2.37 to 7.38), Mainpuri tobacco (3.32, 95% CI = 1.32 to 8.36), and snus (0.86, 95% CI = 0.58 to 1.29).

Conclusion

A significant positive association was observed between SLT use and the risk of oral cancer, in SEAR, EMRs, and among women users.

Implications

The present meta-analysis demonstrates SLT product use and the risk of oral cancer at global level. Moreover, the present analysis provided data on the risk associated with individual SLT product. The results fulfil the gap in the data on independent effect of individual SLT product use on the outcome of oral cancer at global level, conclusively. Chewing SLT products was associated with higher risk of oral cancer than other types of SLT. This can serve as a useful tool for policy makers in forming strict policies in controlling SLT menace. Hence, we propose that in addition to smoking, efforts should be directed towards SLT product cessation as well in reducing oral cancer incidence.
An Improved Technique for Sorting Developmental Stages and Assessing Egg Viability ofGlobodera pallidausing High-Throughput Complex Object Parametric Analyzer and Sorter
Authors: Hajihassani Abolfazl , Dandurand Louise-Marie
Published: April 2018

The Complex Object Parametric Analyzer and Sorter (COPAS) is a large particle flow cytometer designed for analyzing, sorting, and dispensing objects of varying sizes. We explored the potential of using this instrument to analyze and sort various developmental stages and egg viability of Globodera pallida. Cysts were successfully examined and sorted from debris by optimizing side-scatter and red-fluorescence parameters on the COPAS. We were able to separate eggs and second-stage juveniles from samples of mixed population using extinction and time of flight. Separation of live and dead eggs was examined following staining eggs with SYTOX Green and application of time of flight and green peak height. Data were compared with a commonly used viability assay by which eggs were stained with Meldola’s Blue and examined by a microscope. COPAS proved to be effective in assessing viability by detecting two separate gates: live eggs having green fluorescence peaks <190 and dead eggs with the peaks >190. The application of COPAS in combination with SYTOX Green detected a greater number of live eggs than the Meldola’s assay, suggesting that SYTOX Green provided an overestimate of live eggs. COPAS noticeably increased the accuracy and reduced the time required for screening and analyzing nematode populations.
The Asian Citrus Psyllid Host Murraya koenigii Is Immune to Citrus Huanglongbing Pathogen ‘Candidatus Liberibacter asiaticus’
Authors: Beloti Vitor H. , Alves Gustavo R. , Coletta-Filho Helvécio D. , Yamamoto Pedro T.
Published: April 2018

The Asian citrus psyllid (ACP) Diaphorina citri, vector of ‘Candidatus Liberibacter asiaticus’ (CLas), the putative causal agent of citrus Huanglongbing (HLB), is controlled by application of insecticides, which, although effective, has resulted in serious biological imbalances. New management tools are needed, and the technique known as “trap crop” has been attracting attention. A potential plant for use as a trap crop in the management of the ACP is Murraya koenigii (curry leaf). However, for this plant to be used in the field, it needs to be attractive for the vector and must not harbor CLas. To verify the potential of curry leaf as trap crop for the management of HLB, we investigated the ability of D. citri to transmit CLas to M. koenigii, and to other test plants, including M. paniculata (orange jasmine) and cultivar Valencia sweet-orange seedlings. For the tests, the insects were reared on a symptomatic CLas-infected plant and allowed to feed on the three test plant species. The overall maximum transmission rate for the citrus seedlings was 83.3%, and for orange jasmine was 33.3%. Successful transmission of CLas by ACP to the curry-leaf seedlings was not observed, and it was treated as immune to CLas. Supported by the previous results that M. koenigii is attractive for ACP, these results indicate that curry leaf is an excellent candidate for use as a trap crop, to improve the management of the insect vector and consequently of HLB.
Changing Host Photosynthetic, Carbohydrate, and Energy Metabolisms Play Important Roles in Phytoplasma Infection
Authors: Xue Chaoling , Liu Zhiguo , Dai Li , Bu Jiaodi , Liu Mengjun , Zhao Zhihui , Jiang Zihui , Gao Weilin , Zhao Jin
Published: April 2018

Phytoplasmas parasitize plant phloem tissue and cause many economically important plant diseases. Jujube witches’-broom disease is a destructive phytoplasma disease of Chinese jujube (Ziziphus jujuba). To elucidate the influence of phytoplasma on host photosynthetic, carbohydrate and energy metabolisms, four types of jujube tissues showing disease symptoms with different severity were investigated at the structural, physiological, and molecular levels. Quantitative real-time PCR and high-performance liquid chromatography results showed that the down-regulation of genes related to photosynthesis and the lower contents of chlorophyll in diseased leaves. This clearly inhibited the light-harvesting and photosystem II activity of photosynthesis; however, overexpression of genes related to starch, sucrose and glucose synthesis led to higher contents of these carbohydrates. Meanwhile, transmission electron microscopy images revealed that dense amounts of phytoplasmas accumulated in the sieve elements of diseased petiole phloem, and the structure of the grana and stroma lamellae of chloroplasts in the diseased leaves was destroyed. Phytoplasma infection inhibited photosynthesis and led to abnormal carbohydrate accumulation in the diseased leaves. Furthermore, comparative metabolite analysis indicated that phytoplasma infection also stimulated amino acids and energy metabolisms of the diseased leaves. Continually inhibiting the photosynthetic process and stimulating carbohydrate and energy metabolisms of diseased trees may exhaust their nutrients. Our results highlight the importance of changing host metabolisms during the pathogenic process.
Pyramiding for Resistance Durability: Theory and Practice
Authors: Mundt Christopher C.
Published: April 2018

Durable disease resistance is a key component of global food security, and combining resistance genes into “pyramids” is an important way to increase durability of resistance. The mechanisms by which pyramids impart durability are not well known. The traditional view of resistance pyramids considers the use of major resistance gene (R-gene) combinations deployed against pathogens that are primarily asexual. Interestingly, published examples of the successful use of pyramids in the traditional sense are rare. In contrast, most published descriptions of durable pyramids in practice are for cereal rusts, and tend to indicate an association between durability and cultivars combining major R-genes with incompletely expressed, adult plant resistance genes. Pyramids have been investigated experimentally for a diversity of pathogens, and many reduce disease levels below that of the single best gene. Resistance gene combinations have been identified through phenotypic reactions, molecular markers, and challenge against effector genes. As resistance genes do not express equally in all genetic backgrounds, however, a combination of genetic information and phenotypic analyses provide the ideal scenario for testing of putative pyramids. Not all resistance genes contribute equally to pyramids, and approaches have been suggested to identify the best genes and combinations of genes for inclusion. Combining multiple resistance genes into a single plant genotype quickly is a challenge that is being addressed through alternative breeding approaches, as well as through genomics tools such as resistance gene cassettes and gene editing. Experimental and modeling tests of pyramid durability are in their infancy, but have promise to help direct future studies of pyramids. Several areas for further work on resistance gene pyramids are suggested.
Identifying and managing depression in patients with coronary artery disease
Authors: Pragle Aimee Salzer , Salahshor Susan
Published: April 2018

Coronary artery disease (CAD) is the leading cause of death among adults in the United States. Despite advances in cardiac care, patients who have CAD and a diagnosis of depression have higher rates of morbidity and mortality. This article examines the epidemiology, clinical presentation, screening tools, and treatment recommendations for these patients.
Helping a Child with Autism Spectrum Disorder Cope with Divorce
Authors: Reilly Marie , Fogler Jason , Bridgemohan Carolyn , Wiley Melora , Weitzman Carol , Augustyn Marilyn
Published: April 2018

CASE:

Aaron is an 11-year-old boy with autism spectrum disorder (ASD), with cognitive and language skills in the above-average range, whose parents have recently separated. Aaron's mother initiated the separation when she learned that Aaron's father had maintained a relationship with a woman with whom he has a 10-year-old daughter. When Aaron's mother discovered this relationship, she demanded that Aaron's father leave their home.

Aaron's father has moved in with his long-term girlfriend and keeps in contact with Aaron by calling once a day. Neither Aaron's father nor mother has discussed the reason for their separation with Aaron. So far, they have explained their separation by telling Aaron that they are “taking a break.”

Aaron's mother has been deeply hurt by Aaron's father's infidelity and does not want to reconcile with him. Aaron's father recognizes this but would like to continue to have a close relationship with his son. He would also like Aaron to get to know his half-sister.

Aaron's mother seeks guidance regarding how to talk to Aaron about the separation and his father's second family. Given Aaron's diagnosis of ASD, she is particularly concerned about his ability to cope with this unexpected change in circumstances. What is your advice?
Safety and Effectiveness of the Hyaluronic Acid Dermal Filler VYC-17.5L for Nasolabial Folds: Results of a Randomized, Controlled Study
Authors: Monheit Gary , Beer Kenneth , Hardas Bhushan , Grimes Pearl E. , Weichman Barry M. , Lin Vince , Murphy Diane K.
Published: April 2018

BACKGROUND

Juvéderm Vollure XC (VYC-17.5L) belongs to a family of nonanimal hyaluronic acid (HA) gels based on the Vycross technology platform.

OBJECTIVE

To evaluate the safety and effectiveness of VYC-17.5L for correction of moderate to severe nasolabial folds (NLFs) compared with a control HA dermal filler.

METHODS

In this double-blind study, 123 adults with 2 moderate or severe NLFs as measured on the 5-point photonumeric NLF severity scale (NLFSS) were randomized to VYC-17.5L in 1 NLF and control in the contralateral NLF. The coprimary effectiveness end points at Month 6 were difference in improvement in mean NLFSS score for VYC-17.5L versus control and NLFSS responder rate (≥1-point improvement) for VYC-17.5L.

RESULTS

The coprimary effectiveness end points were met. NLFSS scores improved by 1.4 with VYC-17.5L and by 1.3 with control; NLFSS responder rate with VYC-17.5L was 93.2%. More than three-quarters of subjects (82%) treated with VYC-17.5L were very satisfied at Month 6. Investigators reported that VYC-17.5L was smoother and more natural looking and easier to inject and mold than control. VYC-17.5L resulted in significantly fewer severe injection site responses than control.

CONCLUSION

VYC-17.5L was safe and effective for correcting moderate to severe NLFs, with results lasting through 6 months in 93% of subjects.
Circumstances and Signs of Approaching Death in Patients With Amyotrophic Lateral Sclerosis Undergoing Noninvasive Ventilation in Home Care Settings
Authors: Ushikubo Mitsuko
Published: April 2018

The purpose of this study was to elucidate the circumstances and symptoms of patients with amyotrophic lateral sclerosis (ALS) using noninvasive positive pressure ventilation (NPPV) in whom death was approaching, to understand how to provide palliative care to dying patients with ALS receiving NPPV management. The participants were 6 home visiting nurses who were head or subhead nurses of a home visiting nursing agency. Data were collected conducting individual semistructured interviews and then group interviews. The results were based on qualitative analysis of the circumstances of death and prognostication and showed 5 categories: difficulties with knowing about approaching death, several signs and symptoms of knowing about approaching death, importance of feeling prepared and provision of palliative care to die at home, death caused by accident, and fate determined by the caregiver’s ability. Further research is needed to collect rich data about predicting approaching death to improve end-of-life care for NPPV-dependent ALS patients who do not receive sufficient benefits from NPPV.
Being Yourself and Thinking About the Future in People With Motor Neuron Disease: A Grounded Theory of Self-care Processes
Authors: Bassola Barbara , Sansone Valeria Ada , Lusignani Maura
Published: April 2018

Introduction: Self-care is a crucial aspect in the management of people with motor neuron disease (MND). Nurses and healthcare professionals must know the processes used by patients in performing self-care to identify problems and help them. Decision-making processes, self-understanding, and political and social support influence the self-care process in chronic diseases. Little is known about the self-care process in MND. Objective: The aim of this study was to gain insight on the self-care processes in people with MND. Method: A grounded theory method was chosen for this study. Data from interviews were gathered, and a simultaneous comparative analysis was conducted to identify categories and codes. Results: Twenty-one people with spinal muscular atrophy and amyotrophic lateral sclerosis participated in the study. Five categories were identified as grounded in the data. The process starts from “being yourself in the care,” and it develops thanks to “growing and changing” and with a “thinking about the future” approach. “Family role” and “you and who helps you” categories affect the process itself. Conclusion: The self-care process in people with MND is not seen in a daily perspective but changes with the evolution of the disease. For the growing patients with MND, changing, accepting and controlling the disease while deciding autonomously are the foundations of the process.
Frequency of MAP2K1, TP53, and U2AF1 Mutations in BRAF-mutated Langerhans Cell Histiocytosis
Authors: McGinnis Lisa M. , Nybakken Grant , Ma Lisa , Arber Daniel A.
Published: April 2018

Langerhans cell histiocytosis is a proliferative disorder of neoplastic Langerhans cells with activating mutations in the Erk signaling pathway. TP53 and U2AF1 mutations have been implicated in other myelomonocytic malignancies and we hypothesized that mutations in these genes may cosegregate in LCH patients according to BRAF mutation status. Towards this end, we collected cases with a pathologic diagnosis of Langerhans cell histiocytosis from Stanford University Hospital. We analyzed the status of known pathogenic alleles in BRAF, ARAF, TP53, U2AF1, and MAP2K1 on formalin-fixed, paraffin-embedded tissue by direct sequencing. A total of 41 cases (71%) had a BRAFV600E allele detected by sequencing. MAP2K1 mutations were also detected in 5 cases: 3 of 17 (18%) cases with wild-type BRAF and 2 of 41 (5%) cases with BRAFV600E mutations (P=0.14). No cases contained the previously reported ARAF mutation, Q347_A348del. All 10 cases with TP53 mutations contained mutant BRAFV600E allele (P=0.021). Of the 11 cases with U2AF1 mutated, 9 of 41 cases co-occurred with BRAFV600E mutations (P=0.31) and 2 of 17 with wild-type BRAF. Interestingly, we do not find that somatic activating MAP2K1 mutations are mutually exclusive with BRAFV600E mutations as has been reported previously. Instead, our data suggests that MAP2K1 mutations may be present along with BRAF either at diagnosis or may be acquired during disease progression. Furthermore, we demonstrated that likely deleterious TP53 mutations correlate with BRAF mutational status and may play a role in the underlying pathogenesis.
Impressions of Early Mobilization of Critically Ill Children—Clinician, Patient, and Family Perspectives*
Authors: Zheng Katina , Sarti Aimee , Boles Sama , Cameron Saoirse , Carlisi Robert , Clark Heather , Khawaji Adeeb , Awladthani Saif , Al-Harbi Samah , Choong Karen
Published: April 2018

Objectives:

To understand patient, family caregiver, and clinician impressions of early mobilization, the perceived barriers and facilitators to its implementation, and the use of in-bed cycling as a method of mobilization.

Design:

A qualitative study, conducted as part of the Early Exercise in Critically ill Youth and Children, a preliminary Evaluation (wEECYCLE) Pilot randomized controlled trial.

Setting:

McMaster Children’s Hospital PICU, Hamilton, ON, Canada.

Participants:

Clinicians (i.e., physicians, nurses, and physiotherapists), family caregivers, and capable patients age greater than or equal to 8 years old who were enrolled in a clinical trial of early mobilization in critically ill children (wEECYCLE).

Intervention:

Semistructured, face-to-face interviews using a customized interview guide for clinicians, caregivers, and patients respectively, conducted after exposure to the early mobilization intervention.

Measurements and Main Results:

Thirty-seven participants were interviewed (19 family caregivers, four patients, and 14 clinicians). Family caregivers and clinicians described similar interrelated themes representing barriers to mobilization, namely low prioritization of mobilization by the medical team, safety concerns, the lack of physiotherapy resources, and low patient motivation. Key facilitators were family trust in the healthcare team, team engagement, an a priori belief that physical activity is important, and participation in research. Increased familiarity and specific features such as the virtual reality component and ability to execute passive and or active mobilization helped to engage critically ill children in in-bed cycling.

Conclusions:

Clinicians, patients, and families were highly supportive of mobilization in critically ill children; however, concerns were identified with respect to how and when to execute this practice. Understanding key stakeholder perspectives enables the development of strategies to facilitate the implementation of early mobilization and in-bed cycling, not just in the context of a clinical trial but also within the culture of practice in a PICU.
Liposuction Aspirate Fluid Adipose-Derived Stem Cell Injection and Secondary Healing in Fingertip Injury: A Pilot Study
Authors: Tarallo Mauro , Fino Pasquale , Ribuffo Diego , Casella Donata , Toscani Marco , Spalvieri Cristina , Lattanzi Wanda , Di Taranto Giuseppe
Published: April 2018

Background:

Although fingertip injuries account for a high proportion of trauma patients, the correct surgical approach is still debated. The authors compared the traditional conservative approach and a new treatment based on the injection of liposuction aspirate fluid.

Methods:

Forty consecutive patients with a fingertip injury were dichotomized into group A (control group; conservative approach) and group B (treatment group). Group B underwent liposuction, followed by filtration of the lipoaspirate in a closed device (MyStem EVO kit), allowing the nonenzymatic separation of liposuction aspirate fluid, which was then injected at the site of injury. Objective outcomes were time for healing, strength, mobility of joint, and touch and sensory function. Subjective outcomes were cold intolerance, pain, hand disability, and aesthetic result. An aliquot of liposuction aspirate fluid was sent to the laboratory for cellular isolation and analysis by flow cytometry and in vitro differentiation assays.

Results:

The average healing time was 22.3 days in group B and 24.9 days in group A (p < 0.05). Eighty-five percent of group B patients and 67 percent of group A patients scored normal to diminished superficial sensibility (p < 0.05). Group A had higher pain and cold intolerance scores (p < 0.05). Group B scored greater aesthetic and disabilities outcome results (p < 0.05). The cell isolation yield was 8.3 × 105/ml, with a percentage of viable cells of 74.3 percent. Flow cytometry identified a mesenchymal immunophenotype, and in vitro osteogenic and adipogenic induction confirmed the bilinear potential of the isolated cells.

Conclusion:

This clinical study demonstrates for the first time the regenerative potential of liposuction aspirate fluid adipose-derived stem cells in a clinical application.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, II.
Distribution and Performance of Cardiovascular Risk Scores in a Mixed Population of HIV-Infected and Community-Based HIV-Uninfected Individuals in Uganda
Authors: Muiru Anthony N. , Bibangambah Prossy , Hemphill Linda , Sentongo Ruth , Kim June-Ho , Triant Virginia A. , Bangsberg David R. , Tsai Alexander C. , Martin Jeffrey N. , Haberer Jessica E. , Boum Yap , Plutzky Jorge , Hunt Peter W. , Okello Samson , Siedner Mark J.
Published: April 2018

Background:

The utility and validity of cardiovascular diseases (CVD) risk scores are not well studied in sub-Saharan Africa. We compared and correlated CVD risk scores with carotid intima media thickness (c-IMT) among HIV-infected and uninfected people in Uganda.

Methods:

We first calculated CVD risk using the (1) Framingham laboratory–based score; (2) Framingham nonlaboratory score (FRS-BMI); (3) Reynolds risk score; (4) American College of Cardiology and American Heart Association score; and (5) the Data collection on Adverse Effects of Anti-HIV Drugs score. We then compared absolute risk scores and risk categories across each score using Pearson correlation and kappa statistics, respectively. Finally, we fit linear regression models to estimate the strength of association between each risk score and c-IMT.

Results:

Of 205 participants, half were females and median age was 49 years [interquartile range (IQR) 46–53]. Median CD4 count was 430 cells/mm3(IQR 334–546), with median 7 years of antiretroviral therapy exposure (IQR 6.4–7.5). HIV-uninfected participants had a higher median systolic blood pressure (121 vs. 110 mm Hg), prevalent current smokers (18% vs. 4%,P= 0.001), higher median CVD risk scores (P< 0.003), and greater c-IMT (0.68 vs. 0.63,P= 0.003). Overall, FRS-BMI was highly correlated with other risk scores (all rho >0.80). In linear regression models, we found significant correlations between increasing CVD risk and higher c-IMT (P< 0.01 in all models).

Conclusions:

In this cross-sectional study from Uganda, the FRS-BMI correlated well with standard risk scores and c-IMT. HIV-uninfected individuals had higher risk scores than HIV-infected individuals, and the difference seemed to be driven by modifiable factors.
Pneumococcal metabolic adaptation and colonization is regulated by the two-component regulatory system 08
Authors: Gómez-Mejia Alejandro , Gámez Gustavo , Hirschmann Stephanie , Kluger Viktor , Rath Hermann , Böhm Sebastian , Voss Franziska , Kakar Niamatullah , Petruschka Lothar , Völker Uwe , Brückner Reinhold , Mäder Ulrike , Hammerschmidt Sven
Published: April 2018

Streptococcus pneumoniae two-component regulatory systems (TCS) enable adaptation and ensure its maintenance in host environments. This study deciphers the impact of the TCS08 on pneumococcal gene expression and its role in metabolic and pathophysiological processes. Transcriptome analysis and real-time PCR demonstrated a regulatory effect of the TCS08 on genes involved mainly in environmental information processing, intermediary metabolism, and colonization by S. pneumoniae D39 and TIGR4. Striking examples are genes of the fatty acid biosynthesis, arginine-deiminase system, and psa operon encoding the manganese ABC transport system. In silico analysis confirmed that TCS08 is homologous to Staphylococcus aureus SaeRS and a SaeR-like binding motif is displayed in the promotor region of pavB, the upstream gene of the tcs08 operon encoding a surface-exposed adhesin. Indeed, PavB is regulated by the TCS08 as confirmed by immunoblotting and surface abundance assays. Similarly, Pilus-1 of TIGR4 is regulated by TCS08. Finally, in vivo infections using the acute pneumonia and sepsis models showed a strain dependent effect. Loss of function of HK08 or TCS08 attenuated D39 virulence in lung infections. The RR08 deficiency attenuated TIGR4 in pneumonia, while there was no effect on sepsis. In contrast, lack of HK08 procured a highly virulent TIGR4 phenotype in both pneumonia and sepsis infections. Taken together, these data indicate the importance of TCS08 in pneumococcal fitness to adapt to the milieu of the respiratory tract during colonization.

IMPORTANCE

Streptococcus pneumoniae interplays with its environment by using 13 two-component regulatory systems and one orphan response regulator. These systems are involved in the sensing of environmental signals thereby modulating pneumococcal pathophysiology. This study aimed to understand the functional role of genes subject to control by the TCS08. The identified genes play a role in transport of compounds such as sugars or amino acids. In addition, the intermediary metabolism and colonization factors are modulated by TCS08. Thus, TCS08 regulates genes involved in maintaining pneumococcal physiology, transport capacity and adhesive factors to enable optimal colonization, which represents a prerequisite for invasive pneumococcal disease.
Hyper-excitability and hyper-plasticity disrupt cerebellar signal transfer in theIB2KO mouse model of autism
Authors: D'Angelo Egidio Ugo , Soda Teresa , Mapelli Lisa , Locatelli Francesca , Botta Laura , Goldfarb Mitchell , Prestori Francesca
Published: April 2018

Autism spectrum disorders (ASD) are pervasive neurodevelopmental conditions that often involve mutations affecting synaptic mechanisms. Recently, the involvement of cerebellum in ASD has been suggested but the underlying functional alterations remained obscure. We investigated single-neuron and microcircuit properties in IB2 KO mice, which present a cerebellar phenotype associated with ASD. Granule cells showed a larger NMDA receptor-mediated current and enhanced intrinsic excitability raising the excitatory/inhibitory balance. Furthermore, the spatial organization of granular layer responses to mossy fibers shifted from aMexican hattostovepipe hatprofile, with stronger excitation in the core and weaker inhibition in the surround. Finally, the size and extension of long-term synaptic plasticity was remarkably increased. These results show for the first time that hyper-excitability and hyper-plasticity disrupt signal transfer in the granular layer of IB2 KO mice supporting cerebellar involvement in the pathogenesis of ASD.
Revisiting the social brain hypothesis: contest duration depends on loser’s brain size
Authors: van der Bijl Wouter , Buechel Séverine D. , Kotrschal Alexander , Kolm Niclas
Published: April 2018

Background

Brain size is expected to evolve by a balance between cognitive benefits and energetic costs. Several influential hypotheses have suggested that large brains may be especially beneficial in social contexts. Group living and competition may pose unique cognitive challenges to individuals and favor the evolution of increased cognitive ability. Evidence comes from comparative studies on the link between social complexity and brain morphology, but the strength of empirical support has recently been challenged. In addition, the behavioral mechanisms that would link cognitive ability to sociality are rarely studied. Here we take an alternative approach and investigate experimentally how brain size can relate to the social competence of individuals within species, a problem that so far has remained unresolved. We use the unique guppy brain size selection line model system to evaluate whether large brains are advantageous by allowing individuals to better assess their performance in a social contest situation. Based on theoretical literature, we predict that contest duration should depend on the brain size of the loser, as it is the capitulation of the losing individual that ends the fight.

Results

First, we show that studying the movement of competitors during contests allows for precise estimation of the dominance timeline in guppies, even when overt aggression is typically one-sided and delayed. Second, we staged contests between pairs of male that had been artificially selected for large and small relative brain size, with demonstrated differences in cognitive ability. We show that dominance was established much earlier in contests with large-brained losers, whereas the brain size of the winner had no effect. Following our prediction, large-brained individuals gave up more quickly when they were going to lose.

Conclusions

These results suggest that large-brained individuals assess their performance in contests better and that social competence indeed can depend on brain size. Conflict resolution may therefore be an important behavioral mechanism behind macro-evolutionary patterns between sociality and brain size. Since conflict is ubiquitous among group-living animals, the possible effects of the social environment on the evolution of cognition may be more broadly applicable than previously thought.