bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validity of the PROMIS-10 Global Health assessed by telephone and on paper in minor stroke and transient ischaemic attack in the Netherlands
Authors: Lam Ka Hoo , Kwa Vincent I H 
Published: July 2018

ObjectivesDysfunction after transient ischaemic attack (TIA) and minor stroke is often underestimated by clinical measures. Patient-reported outcome measures used in value-based healthcare may help in detecting these problems. The Patient-Reported Outcomes Measurement Information System 10-Question Short Form (PROMIS-10 Global Health) is a concise patient-centred outcome measuring tool proposed for assessing health status in patients who had stroke. This study aims to address the validity of the Dutch PROMIS-10 in patients who had stroke in the Netherlands and also aims to compare telephone versus on-paper assessment.DesignObservational cohort study.SettingSingle-centre hospital in the Netherlands.Participants75 patients who were diagnosed with TIA or minor stroke and discharged without rehabilitation treatment 1 year ago (between December 2014 and January 2016) completed the study.Primary and secondary outcome measuresPROMIS-10 physical (PH) and mental health (MH) scores assessed 1 year poststroke on paper (n=37) and by telephone (n=38) was compared with RAND-36 physical and mental component scores assessed on paper.ResultsPROMIS-10 and RAND-36 correlated significantly in PH, r=0.81 (95% CI 0.69 to 0.88), and MH, r=0.76 (95% CI 0.64 to 0.85). Paper-and-pencil assessed correlations were r=0.87 and 0.79 for PH and MH, respectively. Telephone assessed correlations were r=0.76 and 0.73 for PH and MH, respectively. Internal consistency analysis indicated high reliabilities for both health components of the PROMIS-10, all Cronbach’s α>0.70.ConclusionsThe Dutch PROMIS-10 was found to strongly correlate with the RAND-36. Paper-and-pencil assessment was found to have a higher correlation than telephone assessment. This study provides support for the use of the Dutch PROMIS-10 in assessing health status in patients after TIA and minor stroke.
Depression as a risk factor for the development of rheumatoid arthritis: a population-based cohort study
Authors: Vallerand Isabelle A , Lewinson Ryan T , Frolkis Alexandra D , Lowerison Mark W , Kaplan Gilaad G , Swain Mark G , Bulloch Andrew G M , Patten Scott B , Barnabe Cheryl 
Published: July 2018

ObjectivesMajor depressive disorder (MDD) is associated with increased levels of systemic proinflammatory cytokines, including tumour necrosis factor alpha. As these cytokines are pathogenic in autoimmune diseases such as rheumatoid arthritis (RA), our aim was to explore on a population-level whether MDD increases the risk of developing RA.MethodsA retrospective cohort study was conducted using The Health Improvement Network (THIN) database (from 1986 to 2012). Observation time was recorded for both the MDD and referent cohorts until patients developed RA or were censored. Cox proportional hazards models were used to determine the risk of developing RA among patients with MDD, accounting for age, sex, medical comorbidities, smoking, body mass index and antidepressant use.ResultsA cohort of 403 932 patients with MDD and a referent cohort of 5 339 399 patients without MDD were identified in THIN. Cox proportional hazards models revealed a 31% increased risk of developing RA among those with MDD in an unadjusted model (HR=1.31, 95% CI 1.25 to 1.36, p<0.0001). When adjusting for all covariates, the risk remained significantly increased among those with MDD (HR=1.38, 95% CI 1.31 to 1.46, p<0.0001). Antidepressant use demonstrated a confounding effect that was protective on the association between MDD and RA.ConclusionMDD increased the risk of developing RA by 38%, and antidepressants may decrease this risk in these patients. Future research is necessary to confirm the underlying mechanism of MDD on the pathogenesis of RA.
Software Theater—Teaching Demo-Oriented Prototyping
Authors: Krusche Stephan , Dzvonyar Dora , Xu Han , Bruegge Bernd 
Published: July 2018

Modern capstone courses use agile methods to deliver and demonstrate software early in the project. However, a simple demonstration of functional and static aspects does not provide real-world software usage context, although this is integral to understand software requirements. Software engineering involves capabilities such as creativity, imagination, and interaction, which are typically not emphasized in software engineering courses. A more engaging, dynamic way of presenting software prototypes is needed to demonstrate the context in which the software is used. We combine agile methods, scenario-based design, and theatrical aspects into software theater, an approach to present visionary scenarios using techniques borrowed from theater and film, including props and humor.We describe the software theater workflow, provide examples, and explain patterns to demonstrate its potential. We illustrate two large case studies in which we teach students with varying levels of experience to apply software theater: a capstone course involving industrial customers with 100 students and an interactive lecture-based course with 400 students. We empirically evaluated the use of software theater in both courses. Our evaluations show that students can understand and apply software theater within one semester and that this technique increases their motivation to prepare demonstrations even early in the project. Software theater is more creative, memorable, dynamic, and engaging than normal demonstration techniques and brings fun into education.
A Process-Variation-Tolerant Method for Nanophotonic On-Chip Network
Authors: Xu Yi , Yang Jun , Melhem Rami 
Published: July 2018

Nanophotonic networks, a potential candidate for future networks on-chip, have been challenged for their reliability due to several device-level limitations. One of the main issues is that fabrication errors (a.k.a. process variations) can cause devices to malfunction, rendering communication unreliable. For example, the microring resonator, a preferred optical modulator device, may not resonate at the designated wavelength under process variations (PVs), leading to communication errors and bandwidth loss.
This article proposes a series of solutions to the wavelength drifting problem of microrings and subsequent bandwidth loss problem of an optical network, due to PVs. The objective is to maximize network bandwidth through proper arrangement among microrings and wavelengths with minimum power requirements. Our arrangement, called “MinTrim,” solves this problem using simple integer linear programming, adding supplementary microrings, and allowing flexible assignment of wavelengths to network nodes as long as the resulting network presents maximal bandwidth. Each step is shown to improve bandwidth provisioning with lower power requirements. Evaluations on a sample network show that a baseline network could lose more than 40% bandwidth due to PVs. Such loss can be recovered by MinTrim to produce a network with 98.4% working bandwidth. In addition, the power required for arranging microrings is 39% lower than the baseline. Therefore, MinTrim provides an efficient PV-tolerant solution to improving the reliability of on-chip photonics.
Synaptic drive in spinal motoneurons during scratch network activity
Authors: Guzulaitis Robertas , Hounsgaard Jorn 
Published: July 2018

Synaptic activity in motoneurons may provide unique insight in the relation between functional network activity and behavior. During scratch network activity in an ex vivo preparation from red-eared turtles ( Trachemys scripta elegans), excitatory and inhibitory synaptic current can be separated and quantified in voltage-clamp recordings. With this technique, we confirm the reciprocal synaptic excitation and inhibition in hip flexor motoneurons during ipsilateral scratching and show that out-of-phase inhibition and excitation also characterize hip extensor motoneurons during ipsi- and contralateral scratching. In contrast, inhibition precedes and partly overlaps excitation in hip flexor-like motoneurons and delays depolarization of membrane potential. We conclude that out-of-phase excitation and inhibition during rhythmic network activity is a common feature in spinal motoneurons. NEW & NOTEWORTHY During network activity, the firing pattern of individual neurons is shaped by their intrinsic conductances and synaptic input. Quantification of synaptic input is, therefore, essential to understand how the properties of individual neurons contribute to function and help to reveal the structure of the network. Here, we show how a combination of recording techniques can be used to quantify and compare the pattern of synaptic activity in different groups of motoneurons during rhythmic network activity.
Using gaze behavior to parcellate the explicit and implicit contributions to visuomotor learning
Authors: de Brouwer Anouk J. , Albaghdadi Mohammed , Flanagan J. Randall , Gallivan Jason P. 
Published: July 2018

Successful motor performance relies on our ability to adapt to changes in the environment by learning novel mappings between motor commands and sensory outcomes. Such adaptation is thought to involve two distinct mechanisms: an implicit, error-based component linked to slow learning and an explicit, strategic component linked to fast learning and savings (i.e., faster relearning). Because behavior, at any given moment, is the resultant combination of these two processes, it has remained a challenge to parcellate their relative contributions to performance. The explicit component to visuomotor rotation (VMR) learning has recently been measured by having participants verbally report their aiming strategy used to counteract the rotation. However, this procedure has been shown to magnify the explicit component. Here we tested whether task-specific eye movements, a natural component of reach planning, but poorly studied in motor learning tasks, can provide a direct readout of the state of the explicit component during VMR learning. We show, by placing targets on a visible ring and including a delay between target presentation and reach onset, that individual differences in gaze patterns during sensorimotor learning are linked to participants’ rates of learning and their expression of savings. Specifically, we find that participants who, during reach planning, naturally fixate an aimpoint rotated away from the target location, show faster initial adaptation and readaptation 24 h later. Our results demonstrate that gaze behavior cannot only uniquely identify individuals who implement cognitive strategies during learning but also how their implementation is linked to differences in learning.NEW & NOTEWORTHY Although it is increasingly well appreciated that sensorimotor learning is driven by two separate components, an error-based process and a strategic process, it has remained a challenge to identify their relative contributions to performance. Here we demonstrate that task-specific eye movements provide a direct read-out of explicit strategies during sensorimotor learning in the presence of visual landmarks. We further show that individual differences in gaze behavior are linked to learning rate and savings.
Neuromuscular determinants of slip-induced falls and recoveries in older adults
Authors: Sawers Andrew , Bhatt Tanvi 
Published: July 2018

Is there a neuromuscular basis for falls? If so, it may provide new insight into falls and their assessment and treatment. We hypothesized that falls and recoveries from a laboratory-induced slip would be characterized by differences in multimuscle coordination patterns. Using muscle synergy analysis, we identified different multimuscle coordination patterns between older adults who fell and those who recovered from a laboratory-induced “feet-forward” slip. Participants who fell recruited fewer muscle synergies than participants who recovered. This suggests that a fall may result from recruitment of an inadequate number of muscle synergies to produce the necessary mechanical functions required to maintain balance. Participants who fell also recruited different muscle synergies, including one with high levels of coactivity consistent with a startle-like response. These differences in multimuscle coordination between slip outcomes were not accompanied by differences in slip difficulty or gait kinematics before or during the slip response. The differences in neuromuscular control may therefore reflect differences in sensorimotor control rather than kinematic constraints imposed by the slip, or the musculoskeletal system. Further research is required to test the robustness of these results and their interpretation with respect to additional mechanical variables (e.g., joint torques, ground reaction forces), responses to other fall types (e.g., trips), and within rather than between individuals. NEW & NOTEWORTHY Do falls and recoveries possess distinct neuromuscular features? We identified differences in neuromuscular control between older adults who fell and those who recovered from a “feet-forward” slip. Differences in neuromuscular control were not accompanied by differences in gait or slip kinematics before or during the slip response, suggesting differences in sensorimotor control rather than kinematics dictated the observed differences in neuromuscular control. An analysis of additional mechanical variables is required to confirm this interpretation.
A quantitative framework for motion visibility in human cortex
Authors: Birman Daniel , Gardner Justin L. 
Published: July 2018

Despite the central use of motion visibility to reveal the neural basis of perception, perceptual decision making, and sensory inference there exists no comprehensive quantitative framework establishing how motion visibility parameters modulate human cortical response. Random-dot motion stimuli can be made less visible by reducing image contrast or motion coherence, or by shortening the stimulus duration. Because each of these manipulations modulates the strength of sensory neural responses they have all been extensively used to reveal cognitive and other nonsensory phenomena such as the influence of priors, attention, and choice-history biases. However, each of these manipulations is thought to influence response in different ways across different cortical regions and a comprehensive study is required to interpret this literature. Here, human participants observed random-dot stimuli varying across a large range of contrast, coherence, and stimulus durations as we measured blood-oxygen-level dependent responses. We developed a framework for modeling these responses that quantifies their functional form and sensitivity across areas. Our framework demonstrates the sensitivity of all visual areas to each parameter, with early visual areas V1–V4 showing more parametric sensitivity to changes in contrast and V3A and the human middle temporal area to coherence. Our results suggest that while motion contrast, coherence, and duration share cortical representation, they are encoded with distinct functional forms and sensitivity. Thus, our quantitative framework serves as a reference for interpretation of the vast perceptual literature manipulating these parameters and shows that different manipulations of visibility will have different effects across human visual cortex and need to be interpreted accordingly. NEW & NOTEWORTHY Manipulations of motion visibility have served as a key tool for understanding the neural basis for visual perception. Here we measured human cortical response to changes in visibility across a comprehensive range of motion visibility parameters and modeled these with a quantitative framework. Our quantitative framework can be used as a reference for linking human cortical response to perception and underscores that different manipulations of motion visibility can have greatly different effects on cortical representation.
Modulation of Circulating Protein Biomarkers in Cancer Patients Receiving Bevacizumab and the Anti-Endoglin Antibody, TRC105
Authors: Liu Yingmiao , Starr Mark D. , Brady John C. , Rushing Christel , Pang Herbert , Adams Bonne , Alvarez Delia , Theuer Charles P. , Hurwitz Herbert I. , Nixon Andrew B. 
Published: July 2018

Abstract
TRC105 is an anti-endoglin antibody currently being tested in combination with VEGF inhibitors. In the phase Ib trial, 38 patients were treated with both TRC105 and bevacizumab (BEV), and improved clinical outcomes were observed, despite the fact that 30 patients (79%) were refractory to prior anti-VEGF therapy. Plasma samples were tested for angiogenic and inflammatory biomarkers at baseline and on-treatment. To provide broader context of this combination biomarker study, direct cross-study comparisons were made to biomarker studies previously conducted in patients treated with either BEV or TRC105 monotherapy. Upon treatment with BEV and TRC105, pharmacodynamic changes in response to both BEV (PlGF increase) and TRC105 (soluble endoglin increase) were noted. In addition, distinct patterns of change were identified (similar, opposing, neutralizing). Similar patterns were observed when the combination elicited similar effects to those observed with monotherapy treatment (i.e., decreases of Ang-2, increases of IL6 and VCAM-1). Opposing patterns were observed when the combination led to opposing effects compared with monotherapy treatment (i.e., TGFβ1, PDGF-AA and PDGF-BB, PAI-1). Lastly, neutralizing patterns were observed when one drug led to increase, whereas the other drug led to decrease, and the combination elicited no overall effect on the marker (i.e., VEGF-A, VEGF-D, and IGFBP-3). Patients achieving partial responses or stable disease from the combination exhibited significantly lower expression of E-Cadherin, HGF, ICAM-1, and TSP-2 at baseline. Taken together, the novel biomarker modulations identified may deepen our understanding of the underlying biology in patients treated with BEV and TRC105 compared with either drug alone. Mol Cancer Ther; 17(10); 2248–56. ©2018 AACR.
FTO-Dependent N
6
-Methyladenosine Regulates Cardiac Function During Remodeling and Repair
Authors: Mathiyalagan Prabhu , Adamiak Marta , Mayourian Joshua , Sassi Yassine , Liang Yaxuan , Agarwal Neha , Jha Divya , Zhang Shihong , Kohlbrenner Erik , Chepurko Elena , Chen Jiqiu , Trivieri Maria G. , Singh Rajvir , Bouchareb Rihab , Fish Kenneth , Ishikawa Kiyotake , Lebeche Djamel , Hajjar Roger J. , Sahoo Susmita 
Published: July 2018

Background:

Despite its functional importance in various fundamental bioprocesses, studies of N
6
-methyladenosine (m6A) in the heart are lacking. Here, we show that the FTO (fat mass and obesity-associated protein), an m6A demethylase, plays a critical role in cardiac contractile function during homeostasis, remodeling, and regeneration.

Methods:
We used clinical human samples, preclinical pig and mouse models, and primary cardiomyocyte cell cultures to study the functional role of m6A and FTO in the heart and in cardiomyocytes. We modulated expression of FTO by using adeno-associated virus serotype 9 (in vivo), adenovirus (both in vivo and in vitro), and small interfering RNAs (in vitro) to study its function in regulating cardiomyocyte m6A, calcium dynamics and contractility, and cardiac function postischemia. We performed methylated (m6A) RNA immunoprecipitation sequencing to map transcriptome-wide m6A, and methylated (m6A) RNA immunoprecipitation quantitative polymerase chain reaction assays to map and validate m6A in individual transcripts, in healthy and failing hearts, and in myocytes.

Results:
We discovered that FTO has decreased expression in failing mammalian hearts and hypoxic cardiomyocytes, thereby increasing m6A in RNA and decreasing cardiomyocyte contractile function. Improving expression of FTO in failing mouse hearts attenuated the ischemia-induced increase in m6A and decrease in cardiac contractile function. This is performed by the demethylation activity of FTO, which selectively demethylates cardiac contractile transcripts, thus preventing their degradation and improving their protein expression under ischemia. In addition, we demonstrate that FTO overexpression in mouse models of myocardial infarction decreased fibrosis and enhanced angiogenesis.

Conclusions:
Collectively, our study demonstrates the functional importance of the FTO-dependent cardiac m6A methylome in cardiac contraction during heart failure and provides a novel mechanistic insight into the therapeutic mechanisms of FTO.
Why I am Such a Good Christian: Comments on Gil Anidjar, Blood: A Critique of Christianity
Authors: Landy Francis 
Published: July 2018

AbstractGil Anidjar begins his immensely ambitious bookBloodwith a strange statement/question “Why I am Such a Good Christian.” I begin by examining this question for its implications for cultural hybridity, for myself as well as for Anidjar, through the lens of Anidjar’s concluding discussion of Freud’sMoses and Monotheism. On the way I critically explore Anidjar’s insistence that blood is not a signifier of kinship or ancestry in the Hebrew Bible or in Judaism, and argue that both are in fact much more complex. I suggest also that Christianity has other elements than blood, such as the bread of the Eucharist, and that Anidjar devotes little attention to the differences between Protestant and Catholic Christianity. I conclude by reverting to Freud’s account of an experience of innocence inThe Interpretation of Dreams, as indicative of Freud’s ambivalent position between Judaism and Christianity.
EU Trade Agreements and Human Rights: From Extraterritorial to Territorial Obligations
Authors: Ryngaert Cedric 
Published: July 2018

Abstract
As the European Union (EU) pursues bilateral trade agreements with third states, the EU should be cognizant of the potential ‘extraterritorial’ impacts of these agreements on the enjoyment of human rights in third states when designing and concluding bilateral trade agreements with third states. This article develops a jurisdictional model to determine the geographic scope of EU human rights obligations in the context of the adoption of EU bilateral trade agreements. It is submitted that the doctrine’s classic semantic focus on ‘extraterritoriality’, captured by such constructs as control, impact, or functional competence, clouds rather than illuminates matters of scope of human rights obligations in the context of trade agreements. Instead of looking for justifications for the extraterritorial application of human rights, it is suggested to turn the justificatory gaze to the internal territorial aspects of the human rights risks created by EU decisions on the conclusion of bilateral trade agreements. An internal-territorial model obviates the need for an elaborate conceptualization of ‘extraterritorial’ obligations.