bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insomnie und andere Schlafstörungen
Authors: Gahr M. 
Published: April 2018

ZusammenfassungBeeinträchtigungen des Schlafs gehören zu den sehr häufig berichteten Symptomen. Schlafstörungen können Ursache und Folge von zahlreichen körperlichen Erkrankungen und psychischen Störungen sein und sind mit verminderter Lebensqualität und reduzierter körperlicher und geistiger Leistungsfähigkeit assoziiert. Die narrative Übersichtsarbeit informiert anhand der dritten Auflage der International Classification of Sleep Disorders (ICSD-3) über die Klassifikation und Symptomatik der Schlafstörungen sowie deren Diagnostik und Therapie; der Schwerpunkt liegt dabei auf der Insomnie.
Multiscale mixing patterns in networks
Authors: Peel Leto , Delvenne Jean-Charles , Lambiotte Renaud 
Published: April 2018

SignificanceA central theme of network science is the heterogeneity present in real-life systems, for instance through the absence of a characteristic degree for the nodes. Despite their small-worldness, networks may present other types of heterogeneous patterns, with different parts of the network exhibiting different behaviors. Here we focus on assortativity, a network analogue of correlation used to describe how the presence and absence of edges covaries with the properties of nodes. We design a method to characterize the heterogeneity and local variations of assortativity within a network and exhibit, in a variety of empirical data, rich mixing patterns that would be obscured by summarizing assortativity with a single statistic.
Impact of the tree prior on estimating clock rates during epidemic outbreaks
Authors: Möller Simon , du Plessis Louis , Stadler Tanja 
Published: April 2018

Significance
Genetic sequencing data of pathogens allow one to quantify the evolutionary rate together with epidemiological dynamics using Bayesian phylodynamic methods. Such tools are particularly useful for obtaining a timely understanding of newly emerging epidemic outbreaks. During the West African Ebola virus disease epidemic, an unusually high evolutionary rate was initially estimated, promoting discussions regarding the potential danger of the strain quickly evolving into an even more dangerous virus. We show here that such high evolutionary rates are not necessarily real but can stem from methodological biases in the analyses. While most analyses of epidemic outbreak data are performed such that these biases may be present, we suggest a solution to overcome these biases in the future.
Mechanosensitivity of Jagged–Notch signaling can induce a switch-type behavior in vascular homeostasis
Authors: Loerakker Sandra , Stassen Oscar M. J. A. , ter Huurne Fleur M. , Boareto Marcelo , Bouten Carlijn V. C. , Sahlgren Cecilia M. 
Published: April 2018

Significance
Notch signaling and hemodynamics are widely known to regulate arterial morphogenesis, remodeling, and homeostasis. Recent studies suggest that Notch signaling and mechanics interact in vascular remodeling, but the impact on vascular homeostasis is still unclear. Here, using a computational–experimental approach, we show that expression of Notch ligands, receptors, and target genes are down-regulated with mechanical strain. Incorporation of these results in a computational model of the arterial wall reveals that this mechanosensitivity leads to a sudden transition from synthetic toward contractile smooth muscle cells at a certain wall thickness, which varies per arterial location and closely agrees with reported anatomical data. This result provides an explanation for how mechanical forces can regulate arterial morphogenesis and homeostasis through Notch signaling.
Spatial eye–hand coordination during bimanual reaching is not systematically coded in either LIP or PRR
Authors: Mooshagian Eric , Snyder Lawrence H. 
Published: April 2018

Significance
When we reach for something, we also look at it. If we reach for two objects at once, one with each hand, we look first at one and then the other. It is not known which brain areas underlie this coordination. We studied two parietal areas known to be involved in eye and arm movements. Neither area was sensitive to the order in which the targets were looked at. This implies that coordinated saccades are driven by downstream areas and not by the parietal cortex as is commonly assumed.
Microbes vs. chemistry in the origin of the anaerobic gut lumen
Authors: Friedman Elliot S. , Bittinger Kyle , Esipova Tatiana V. , Hou Likai , Chau Lillian , Jiang Jack , Mesaros Clementina , Lund Peder J. , Liang Xue , FitzGerald Garret A. , Goulian Mark , Lee Daeyeon , Garcia Benjamin A. , Blair Ian A. , Vinogradov Sergei A. , Wu Gary D. 
Published: April 2018

Significance
It is generally thought that the gut microbes consume oxygen and maintain the lumen in a deeply anaerobic state. However, we found that the gut of germ-free mice is also deeply anaerobic, suggesting that there exist other mechanisms responsible for oxygen consumption in addition to the microbes’ respiration. These mechanisms comprise oxidative reactions, such as the oxidation of lipids and other organic substrates. Both the microbiota and the oxidative chemistry regulate luminal oxygen levels that in turn influence the composition of the microbial communities throughout the intestinal tract.
Label-free and charge-sensitive dynamic imaging of lipid membrane hydration on millisecond time scales
Authors: Tarun Orly B. , Hannesschläger Christof , Pohl Peter , Roke Sylvie 
Published: April 2018

Significance
Lipid bilayer membranes are responsible for compartmentalization, signaling, transport, and flow of charge in living cells. Membranes self-assemble in aqueous solutions. Without a hydrating environment, membranes cannot exist. It is therefore surprising to note that the hydrating water is neglected in most membrane-related studies. We imaged membrane-bound oriented water by means of label-free second harmonic microscopy. We tracked, on millisecond time scales, membrane domain diffusion of condensed charged lipid domains, domain structure, and the spatial distribution of charge. Real-time electrostatic membrane potential maps were constructed using nonlinear optical theory. The spatiotemporal fluctuation in the membrane potential is surprisingly large and reveals the importance of charge fluctuations on membranes.
Flavivirus internalization is regulated by a size-dependent endocytic pathway
Authors: Hackett Brent A. , Cherry Sara 
Published: April 2018

Significance
Flaviviruses are a globally important group of human viral pathogens. These viruses enter cells by hijacking an endocytic pathway, clathrin-mediated endocytosis, used by cells to take up growth factors and nutrients. While most cargo is small, virions are large, and we identified host factors specifically required for the internalization of large cargo including these viruses. These studies define a set of requirements for viral internalization and which may be amenable to therapeutic interventions.
Dramatic pressure-sensitive ion conduction in conical nanopores
Authors: Jubin Laetitia , Poggioli Anthony , Siria Alessandro , Bocquet Lydéric 
Published: April 2018

Significance
The domain of nanofluidics, exploring fluid and ionic transport at the nanoscale, has made tremendous progress recently. However, transport in artificial systems remains as yet unable to reproduce the richness and complexity of the advanced functionalities exhibited in Nature, such as mechanosensitive channel activation, ionic pumps, etc. Here we demonstrate experimentally and theoretically a mechanosensitive ionic transistor effect in conical nanopores, in which the ionic conduction is found to be activated or inhibited by a mechanical stimulus. Such behavior is a fundamental building block for reproducing the advanced transport functionalities found in Nature.
m6ASNP: a tool for annotating genetic variants by m6A function
Authors: Jiang Shuai , Xie Yubin , He Zhihao , Zhang Ya , Zhao Yuli , Chen Li , Zheng Yueyuan , Miao Yanyan , Zuo Zhixiang , Ren Jian 
Published: April 2018

Abstract

Background
Large-scale genome sequencing projects have identified many genetic variants for diverse diseases. A major goal of these projects is to characterize these genetic variants to provide insight into their function and roles in diseases. N6-methyladenosine (m6A) is one of the most abundant RNA modifications in eukaryotes. Recent studies have revealed that aberrant m6A modifications are involved in many diseases.

Findings
In this study, we present a user-friendly web server called “m6ASNP” that is dedicated to the identification of genetic variants that target m6A modification sites. A random forest model was implemented in m6ASNP to predict whether the methylation status of an m6A site is altered by the variants that surround the site. In m6ASNP, genetic variants in a standard variant call format (VCF) are accepted as the input data, and the output includes an interactive table that contains the genetic variants annotated by m6A function. In addition, statistical diagrams and a genome browser are provided to visualize the characteristics and to annotate the genetic variants.

Conclusions
We believe that m6ASNP is a very convenient tool that can be used to boost further functional studies investigating genetic variants. The web server “m6ASNP” is implemented in JAVA and PHP and is freely available at [60].
Acute Onset of Pneumococcal Pneumonia Following Instrumentation of the Respiratory Tract
Authors: Gardner Julianna G , Rueda Adriana M , Musher Daniel M 
Published: April 2018

Abstract
We describe 22 patients who developed pneumococcal pneumonia within 96 hours of respiratory tract instrumentation. In 59% of cases, the time to onset of symptoms was &lt;24 hours. Instrumentation bypasses normal protective barriers and carries organisms directly to the lower airways, leading to the rapid development of pneumonia.
How to cope with food allergy symptoms?
Authors: Deschildre Antoine , Lejeune Stéphanie 
Published: April 2018

Purpose of review
Food allergy symptoms may involve a wide variety of organs (skin, gastrointestinal tract, and eyes) and systems (respiratory, circulatory, and neurological). They are often associated. Their severity ranges from mild to potentially life-threatening reactions and the presentation from acute to chronic.

Recent findings
Food allergies have been the focus of multiple studies, position papers, and guidelines in recent years. They have defined an approach in classifying symptoms as mild to anaphylactic, distinguishing objective from subjective symptoms, and describing their heterogeneity, specific phenotypes or syndromes (e.g., lipid transfer protein syndrome or pollen food syndrome). Cofactors can also influence food allergy reactions. Symptoms of non-IgE-gastrointestinal food allergies, illustrated by eosinophilic esophagitis and food-protein-induced enterocolitis syndrome, are also now better understood and defined. Improvement in the knowledge of food allergy symptoms is crucial for correct diagnosis and a personalized treatment approach.

Summary
Through a better description and understanding of symptoms, the diversity of food allergies is now better known. The next step is to harmonize symptom assessment not only for clinicians but also for patients, researchers, and public health stakeholders, to describe food allergy phenotypes and their underlying mechanisms and endotypes, to develop targeted management.
Clinical Predictors of Survival and Functional Outcome of Stroke Patients Admitted to Critical Care*
Authors: van Valburg Mariëlle K. , Arbous M. Sesmu , Georgieva Milena , Brealey David A. , Singer Mervyn , Geerts Bart F. 
Published: April 2018

Objectives:
To determine the predictive value of commonly used clinical variables upon ICU admission for long-term all-cause mortality and functional outcome of adult stroke patients admitted to the ICU.

Design:
Retrospective observational cohort study.

Setting:
General and neurosurgical ICUs of the University College London Hospitals in North Central London.

Patients:
All adult ICU patients with a clinical diagnosis of acute stroke admitted between February 2010 and May 2012.

Interventions:
None.

Measurements and Main Results:
Demographic and clinical data concerning the first 24 hours after ICU admission were obtained. Patients were followed until February 2016 to assess long-term survival. Functional outcome was determined using the modified Rankin Scale. We evaluated 131 critically ill stroke patients, with a median (interquartile range) age of 70 years (55–78 yr). One-year mortality rate was 52.7%. Surviving patients were followed up over a median (interquartile range) period of 4.3 years (4.0–4.8 yr). The multivariable model that best predicted long-term all-cause mortality indicated that mortality of critically ill stroke patients was predicted by high Acute Physiology and Chronic Health Evaluation II score, impaired consciousness (Glasgow Coma Scale score ≤ 8) as reason for ICU admission, low Glasgow Coma Scale sum score after 24 hours, and absence of brainstem reflexes. Long-term independent functional status occurred in 30.9% of surviving patients and was predicted by low Acute Physiology and Chronic Health Evaluation II score, high Glasgow Coma Scale sum score at ICU admission, and absence of mass effect on CT scan.

Conclusions:
Mortality in critically ill stroke patients is high and occurs most often shortly after the event. Less than one in three surviving patients is able to function independently after 1 year. This study has identified several clinical variables that predict long-term all-cause mortality and functional outcome among critically ill stroke patients and found that mainly acute physiologic disturbance and absolute values of neurologic clinical assessment are predictive.
Simultaneous Quantification of Adalimumab and Infliximab in Human Plasma by Liquid Chromatography–Tandem Mass Spectrometry
Authors: Jourdil Jean-François , Némoz Benjamin , Gautier-Veyret Elodie , Romero Charlotte , Stanke-Labesque Françoise 
Published: April 2018

Background:
Adalimumab (ADA) and infliximab (IFX) are therapeutic monoclonal antibodies targeting tumor necrosis factor-alpha (TNFα). They are used to treat inflammatory diseases. Clinical trials have suggested that therapeutic drug monitoring for ADA or IFX could improve treatment response and cost effectiveness. However, ADA and IFX were quantified by ELISA in all these studies, and the discrepancies between the results obtained raise questions about their reliability. We describe here the validation of a liquid chromatography–tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantification of ADA and IFX in human samples.

Methods:
Full-length antibodies labeled with stable isotopes were added to plasma samples as an internal standard. Samples were then prepared using Mass Spectrometry Immunoassay followed by trypsin digestion before ADA and IFX quantification by LC-MS/MS. ADA and IFX were quantified in serum from patients treated with ADA (n = 21) or IFX (n = 22), and the concentrations obtained were compared with those obtained with a commercial ELISA kit.

Results:
The chromatography run lasted 8.6 minutes, and the quantification range was 1–26 mg/L. The method was reproducible, repeatable, and accurate. For both levels of internal quality control, for ADA and IFX, interday and intraday coefficients of variation and accuracies were all within 15%, in accordance with FDA recommendations. No significant cross-contamination effect was noted. Good agreement was found between LC-MS/MS and ELISA results, for both ADA and IFX.

Conclusions:
This LC-MS/MS method can be used for the quantification of ADA and IFX in a single analytical run and for the optimization of LC-MS/MS resource use in clinical pharmacology laboratories.
Pressure-induced referred pain areas are more expansive in individuals with a recovered fracture
Authors: Doménech-García Víctor , Skuli Palsson Thorvaldur , Boudreau Shellie Ann , Herrero Pablo , Graven-Nielsen Thomas 
Published: April 2018

Abstract
Musculoskeletal trauma and pain can sensitize central pain mechanisms, but whether these normalize on recovery is unknown. This study compared the extent of pain referral in individuals recovered from a musculoskeletal trauma and healthy controls. Twenty pain-free participants recovered from a shoulder fracture and 20 age-/sex-matched controls participated in 2 experimental sessions (day-0 and day-1) separated by 24 hours. On both days, pressure pain thresholds were measured bilaterally at infraspinatus, supraspinatus, trapezius, and gastrocnemius muscles. Referred pain towards the shoulder region was induced by a 60-second pressure stimulation (pressure pain threshold + 20%) at the infraspinatus muscle and recorded on an electronic body chart. After day-0 assessments, delayed onset muscle soreness (DOMS) was induced to challenge the pain systems by exercising the external rotators of the recovered/dominant shoulder. The size of pressure-induced pain referral on day-0 did not differ between groups, although there was a tendency for a smaller referred pain area in recovered group. Pressure pain thresholds at the infraspinatus muscle on the DOMS side were reduced on day-1 in both groups (P = 0.03). An expansion of pressure-induced pain referral was found in both groups following the DOMS protocol on day-1 (P = 0.05) with a relatively larger expansion (P = 0.05) and higher frequency of pain in the shoulder (P = 0.04) in the recovered pain group. After complete recovery and absence of pain symptoms after a fracture, central pain mechanisms seem to normalize in the region of the trauma after recovery but when sensitized a heightened response can emerge. Such mechanisms could be important for recurrence of pain conditions.
Comparison of the psychometric properties of 3 pain scales used in the pediatric emergency department: Visual Analogue Scale, Faces Pain Scale-Revised, and Colour Analogue Scale
Authors: Le May Sylvie , Ballard Ariane , Khadra Christelle , Gouin Serge , Plint Amy C. , Villeneuve Edith , Mâsse Benoit , Tsze Daniel S. , Neto Gina , Drendel Amy L. , Auclair Marie-Christine , McGrath Patrick J. , Ali Samina 
Published: April 2018

Abstract
Appropriate pain measurement relies on the use of valid, reliable tools. The aim of this study was to determine and compare the psychometric properties of 3 self-reported pain scales commonly used in the pediatric emergency department (ED). The inclusion criteria were children aged 6 to 17 years presenting to the ED with a musculoskeletal injury and self-reported pain scores ≥30 mm on the mechanical Visual Analogue Scale (VAS). Self-reported pain intensity was assessed using the mechanical VAS, Faces Pain Scale-Revised (FPS-R), and Colour Analogue Scale (CAS). Convergent validity was assessed by Pearson correlations and the Bland–Altman method; responsiveness to change was assessed using paired sample t tests and standardized mean responses; and reliability was estimated using relative and absolute indices. A total of 456 participants were included, with a mean age of 11.9 years ± 2.7 and a majority were boys (252/456, 55.3%). Correlations between each pair of scales were 0.78 (VAS/FPS-R), 0.92 (VAS/CAS), and 0.79 (CAS/FPS-R). Limits of agreement (95% confidence interval) were −3.77 to 2.33 (VAS/FPS-R), −1.74 to 1.75 (VAS/CAS), and −2.21 to 3.62 (CAS/FPS-R). Responsiveness to change was demonstrated by significant differences in mean pain scores among the scales (P < 0.0001). Intraclass correlation coefficient and coefficient of repeatability estimates suggested acceptable reliability for the 3 scales at, respectively, 0.79 and ±2.29 (VAS), 0.82 and ±2.07 (CAS), and 0.76 and ±2.82 (FPS-R). The scales demonstrated good psychometric properties for children with acute pain in the ED. The VAS and CAS showed a strong convergent validity, whereas FPS-R was not in agreement with the other scales.
Extravascular lung water measurements in acute respiratory distress syndrome: why, how, and when?
Authors: Tagami Takashi , Ong Marcus Eng Hock 
Published: April 2018

Purpose of review
Increase in pulmonary vascular permeability accompanied with accumulation of excess extravascular lung water (EVLW) is the hallmark of acute respiratory distress syndrome (ARDS). Currently, EVLW and pulmonary vascular permeability index (PVPI) can be quantitatively measured using the transpulmonary thermodilution (TPTD) technique. We will clarify why, how, and when EVLW and PVPI measurements should be performed.

Recent findings
Although the Berlin criteria of ARDS are simple and widely used, several criticisms of them have been published. The last 2 decades have witnessed the introduction and evolution of the TPTD technique for measuring EVLW and PVPI. Several publications have recommended to evaluate EVLW and the PVPI during the treatment of critically ill patients. Accurate and objective diagnoses can be made for ARDS patients using EVLW and PVPI. EVLW more than 10 ml/kg is a reasonable criterion for pulmonary edema, and EVLW more than 15 ml/kg for a severe condition. In addition to EVLW more than 10 mL/kg, PVPI more than three suggests increased vascular permeability (i.e., ARDS), and PVPI less than 2 represent normal vascular permeability (i.e., cardiogenic pulmonary edema).

Summary
EVLW and PVPI measurement will open the door to future ARDS clinical practice and research, and have potential to be included in the future ARDS definition.
Barrett Esophagus Length, Nodularity, and Low-grade Dysplasia are Predictive of Progression to Esophageal Adenocarcinoma
Authors: Solanky Dipesh , Krishnamoorthi Rajesh , Crews Nicholas , Johnson Michele , Wang Kenneth , Wolfsen Herbert , Fleischer David , Ramirez Francisco C. , Katzka David , Buttar Navtej , Iyer Prasad G. 
Published: April 2018

Goals:
To investigate factors predictive of progression from nondysplastic Barrett esophagus (NDBE) or low-grade dysplasia (LGD) to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) using a large, prospective cohort of patients, wherein all esophageal biopsies undergo expert gastrointestinal pathologist review.

Background:
Efficacy and cost-effectiveness of endoscopic surveillance to detect incident EAC in the setting of Barrett esophagus (BE), particularly in NDBE patients, is questioned. Previous studies have reported factors predictive of progression to EAC to guide surveillance intervals, but their strength is limited by small sample size and absence of expert gastrointestinal pathologist involvement in esophageal biopsy review.

Study:
NDBE and LGD subjects were identified from a prospective registry in a tertiary care center. “Progressors” were BE subjects who developed HGD/EAC>12 months after the initial NDBE or LGD diagnosis. Cox proportional hazards model were used to identify predictors of progression.

Results:
In total, 318 with NDBE and 301 with BE-LGD (mean age, 62.6 y, 85% male) were included. The mean follow-up was 5.3 years. The 7 NDBE and 21 LGD subjects progressed to HGD/EAC. BE length [hazards ratio (HR), 1.16; 95% confidence interval (CI), 1.03-1.29], presence of nodularity (HR, 4.98; 95% CI, 1.80-11.7), and baseline LGD (HR, 2.57; 95% CI, 1.13-6.57) were significant predictors of progression on multivariate analysis.

Conclusions:
In this well-defined cohort of NDBE and BE-LGD subjects, BE length, presence of LGD, and nodularity were independent predictors of progression to HGD/EAC. These factors may aid in identifying high-risk patients who may benefit from closer endoscopic surveillance/therapy.