bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the electronic self-report Symptom Screening in Pediatrics Tool (SSPedi)
Authors: O'Sullivan Cathy , Lee Dupuis L , Gibson Paul , Johnston Donna L , Baggott Christina , Portwine Carol , Spiegler Brenda , Kuczynski Susan , Tomlinson Deborah , Tomlinson George A , Sung Lillian 
Published: November 2016

ObjectiveWe previously developed the paper-based Symptom Screening in Pediatrics Tool (SSPedi) designed for paediatric cancer symptom screening. Objectives were to evaluate and refine the electronic mobile application (app) of SSPedi using the opinions of children with cancer.MethodsParticipants were children 8–18 years of age with cancer. Participants completed electronic SSPedi on their own and then responded to semistructured questions to determine whether they found electronic SSPedi easy or difficult to complete and understand, understood and liked the app features (audio and animation), and understood previously difficult to understand concepts with the introduction of a help menu. After each group of 10 children, responses were reviewed to determine whether modifications were required.Results20 children evaluated electronic SSPedi. None found electronic SSPedi difficult to complete or understand. All children understood the app features and each of the 4 more difficult to understand concepts after using the help menu. 19 of 20 children thought the app was a good way to communicate with doctors and nurses.ConclusionsWe finalised an electronic version of SSPedi that is easy to use and understand with features specifically designed to facilitate child self-report. Future work will evaluate the psychometric properties of electronic SSPedi.
Alterations in the epithelial stem cell compartment could contribute to permanent changes in the mucosa of patients with ulcerative colitis
Authors: Dotti Isabella , Mora-Buch Rut , Ferrer-Picón Elena , Planell Núria , Jung Peter , Masamunt M Carme , Leal Raquel Franco , Martín de Carpi Javier , Llach Josep , Ordás Ingrid , Batlle Eduard , Panés Julián , Salas Azucena 
Published: November 2016

ObjectiveUC is a chronic inflammatory disease of the colonic mucosa. Growing evidence supports a role for epithelial cell defects in driving pathology. Moreover, long-lasting changes in the epithelial barrier have been reported in quiescent UC. Our aim was to investigate whether epithelial cell defects could originate from changes in the epithelial compartment imprinted by the disease.DesignEpithelial organoid cultures (EpOCs) were expanded ex vivo from the intestinal crypts of non-IBD controls and patients with UC. EpOCs were induced to differentiate (d-EpOCs), and the total RNA was extracted for microarray and quantitative real-time PCR (qPCR) analyses. Whole intestinal samples were used to determine mRNA expression by qPCR, or protein localisation by immunostaining.ResultsEpOCs from patients with UC maintained self-renewal potential and the capability to give rise to differentiated epithelial cell lineages comparable with control EpOCs. Nonetheless, a group of genes was differentially regulated in the EpOCs and d-EpOCs of patients with UC, including genes associated with antimicrobial defence (ie,LYZ,PLA2G2A), with secretory (ie,ZG16,CLCA1) and absorptive (ie,AQP8,MUC12) functions, and with a gastric phenotype (ie,ANXA10,CLDN18andLYZ). A high rate of concordance was found in the expression profiles of the organoid cultures and whole colonic tissues from patients with UC.ConclusionsPermanent changes in the colonic epithelium of patients with UC could be promoted by alterations imprinted in the stem cell compartment. These changes may contribute to perpetuation of the disease.
Prevalence and incidence of gout in southern Sweden from the socioeconomic perspective
Authors: Kapetanovic Meliha C , Hameed Mohaned , Turkiewicz Aleksandra , Neogi Tuhina , Saxne Tore , Jacobsson Lennart , Englund Martin 
Published: November 2016

ObjectivesTo estimate the prevalence and cumulative incidence of gout in southern Sweden with respect to socioeconomic status.MethodsAmong residents of Skåne region in the year 2013 (total population 1.3 million), adult persons (age 18 years +) who between 1998 and 2013 received a diagnosis of gout (International Classification of Disease 10th Edition (ICD-10) code M10) by any physician were identified using the Skåne Healthcare Register. We calculated the point prevalence by end of 2013 and annual cumulative incidence in 2013 standardised to the whole Skåne population according to sex, individual information on occupation (white collar/blue collar), income (low/middle/high) and level of education (primary school/high school/university).ResultsThe crude 2013 point prevalence of gout and 2013 cumulative incidence (95% CI) were 1.69% (1.66% to 1.71%) and 24 cases per 10 000 persons (23–25), respectively. Compared to women, men had higher point prevalence (2.44% (2.40% to 2.49%) vs 0.96% (0.93% to 0.98%)) and higher annual cumulative incidence (33 cases per 10 000 (32–35)) versus 15 (14–16)). These figures increased with higher age but decreased with higher level of education, being the lowest in individuals with a university degree. Persons with middle income had highest point prevalence and cumulative incidence of gout, while those with white collar occupations had the lowest.ConclusionsGout is the most common inflammatory arthritis in southern Sweden with a prevalence of ∼1.7% in the adult population. There is a socioeconomic gradient with more gout present in the lower level of education and with more manual labour.
Impact of feeding and housing systems on disease incidence in dairy calves
Authors: Curtis G. C. , Argo C. McG. , Jones D. , Grove‐White D. H. 
Published: November 2016

Contentious issues in calf rearing include milk feeding level and single versus group housing. The current study was performed on a high‐producing 170 Holstein cow dairy farm to investigate the impact of nutrition and housing on disease incidence. Calves (n=100) were allocated in birth order to one of two commonly used feeding strategies. Group A calves were group housed from birth and fed ad libitum milk replacer (MR) via a computerised machine using a single teat, with weaning commencing at 63 days. Group R calves were initially housed in individual pens receiving 2.5 litres of MR twice daily via a bucket until three weeks of age when they were group housed and fed 3 litres of MR twice daily via a group trough with weaning commencing at 56 days. In total, 80 (80 per cent) calves suffered from at least one incident of disease during the period from birth to 12 weeks. Group A calves had a greater risk of disease than group R calves (diarrhoea: OR 3.86 (95 per cent CI 1.67 to 8.9); pneumonia: OR 5.80 (95 per cent CI 2.33 to 14.44)). There was a 5.1 per cent incidence of failure of passive transfer of Ig assessed via measurement of plasma total protein concentrations at 48 hours of age. It is hypothesised that the increased diarrhoea risk in group A calves was most likely associated with group housing, while the increased pneumonia risk was associated with the use of a single teat allowing increased transmission of pathogens from calf to calf.
Right prefrontal cortex transcranial direct current stimulation enhances multi-day savings in sensorimotor adaptation
Authors: Seidler Rachael D. , Gluskin Brittany S. , Greeley Brian 
Published: November 2016

We have previously reported that visuospatial working memory performance and magnitude of activation in the right dorsolateral prefrontal cortex predict the rate of visuomotor adaptation. Recent behavioral studies suggest that sensorimotor savings, or faster relearning on second exposure to a task, are due to recall of these early, strategic components of adaptation. In the present study we applied anodal transcranial direct current stimulation to right or left prefrontal cortex or left motor cortex. We found that all groups adapted dart throwing movements while wearing prism lenses at the same rate as subjects receiving sham stimulation on day 1. On test day 2, which was conducted a few days later, the right prefrontal and left motor cortex groups adapted faster than the sham group. Moreover, only the right prefrontal group exhibited greater savings, expressed as a greater difference between day 1 and day 2 errors, compared with sham stimulation. These findings support the hypothesis that the right prefrontal cortex contributes to sensorimotor adaptation and savings. NEW & NOTEWORTHY We have previously reported that visuospatial working memory performance and magnitude of activation in the right dorsolateral prefrontal cortex predict the rate of manual visuomotor adaptation. Sensorimotor savings, or faster adaptation to a previously experienced perturbation, has been recently linked to cognitive processes. We show that facilitating the right prefrontal cortex with anodal transcranial direct current stimulation enhances sensorimotor savings compared with sham stimulation.
Go-activation endures following the presentation of a stop-signal: evidence from startle
Authors: Drummond Neil M. , Cressman Erin K. , Carlsen Anthony N. 
Published: November 2016

It has been proposed that, in a stop-signal task (SST), independent go- and stop-processes “race” to control behavior. If the go-process wins, an overt response is produced, whereas, if the stop-process wins, the response is withheld. One prediction that follows from this proposal is that, if the activation associated with one process is enhanced, it is more likely to win the race. We looked to determine whether these initiation and inhibition processes (and thus response outcomes) could be manipulated by using a startling acoustic stimulus (SAS), which has been shown to provide additional response activation. In the present study, participants were to respond to a visual go-stimulus; however, if a subsequent stop-signal appeared, they were to inhibit the response. The stop-signal was presented at a delay corresponding to a probability of responding of 0.4 (determined from a baseline block of trials). On stop-trials, a SAS was presented either simultaneously with the go-signal or stop-signal or 100, 150, or 200 ms following the stop-signal. Results showed that presenting a SAS during stop-trials led to an increase in probability of responding when presented with or following the stop-signal. The latency of SAS responses at the stop-signal + 150 ms and stop-signal + 200 ms probe times suggests that they would have been voluntarily inhibited but instead were involuntarily initiated by the SAS. Thus results demonstrate that go-activation endures even 200 ms following a stop-signal and remains accessible well after the response has been inhibited, providing evidence against a winner-take-all race between independent go- and stop-processes. NEW & NOTEWORTHY In this study, a startling acoustic stimulus (SAS) was used to determine whether response outcome could be manipulated in a stop-signal task. Results revealed that presenting a SAS during stop-signal trials led to an increase in probability of responding even when presented 200 ms following the stop-signal. The latency of SAS responses indicates that go-activation remains accessible and modifiable well after the response is voluntarily inhibited, providing evidence against an irrevocable commitment to inhibition.
Contrast sensitivity, V1 neural activity, and natural vision
Authors: Niemeyer James E. , Paradiso Michael A. 
Published: November 2016

Contrast sensitivity is fundamental to natural visual processing and an important tool for characterizing both visual function and clinical disorders. We simultaneously measured contrast sensitivity and neural contrast response functions and compared measurements in common laboratory conditions with naturalistic conditions. In typical experiments, a subject holds fixation and a stimulus is flashed on, whereas in natural vision, saccades bring stimuli into view. Motivated by our previous V1 findings, we tested the hypothesis that perceptual contrast sensitivity is lower in natural vision and that this effect is associated with corresponding changes in V1 activity. We found that contrast sensitivity and V1 activity are correlated and that the relationship is similar in laboratory and naturalistic paradigms. However, in the more natural situation, contrast sensitivity is reduced up to 25% compared with that in a standard fixation paradigm, particularly at lower spatial frequencies, and this effect correlates with significant reductions in V1 responses. Our data suggest that these reductions in natural vision result from fast adaptation on one fixation that lowers the response on a subsequent fixation. This is the first demonstration of rapid, natural-image adaptation that carries across saccades, a process that appears to constantly influence visual sensitivity in natural vision. NEW & NOTEWORTHY Visual sensitivity and activity in brain area V1 were studied in a paradigm that included saccadic eye movements and natural visual input. V1 responses and contrast sensitivity were significantly reduced compared with results in common laboratory paradigms. The parallel neural and perceptual effects of eye movements and stimulus complexity appear to be due to a form of rapid adaptation that carries across saccades.
Preclinical Evaluation of Chimeric Antigen Receptors Targeting CD70-Expressing Cancers
Authors: Wang Qiong J. , Yu Zhiya , Hanada Ken-ichi , Patel Krishna , Kleiner David , Restifo Nicholas P. , Yang James C. 
Published: November 2016

AbstractPurpose: CD70 expression in normal tissues is restricted to activated lymphoid tissues. Targeting CD70 on CD70-expressing tumors could mediate “on-target, off-tumor” toxicity. This study was to evaluate the feasibility and safety of using anti-human CD70 CARs to treat cancer patients whose tumors express CD70.Experimental Design: Seven anti-human CD70 CARs with binding moieties from human CD27 combined with CD3-zeta and different costimulatory domains from CD28 and/or 41BB were constructed. In vitro functionality of these receptors was compared and in vivo treatment efficacy was evaluated in a xenograft mouse model. A homologous, all murine anti-CD70 CAR model was also used to assess treatment-related toxicities.Results: The CAR consisting of the extracellular binding portion of CD27 fused with 41BB and CD3-zeta (trCD27-41BB-zeta) conferred the highest IFNγ production against CD70-expressing tumors in vitro, and NSG mice bearing established CD70-expressing human tumors could be cured by human lymphocytes transduced with this CAR. In the murine CD27-CD3-zeta CAR model, significant reduction of established tumors and prolonged survival were achieved using CAR-transduced splenocytes in a dose-dependent manner. Host preirradiation enhanced treatment efficacy but increased treatment-related toxicities such as transient weight loss and hematopoetic suppression. The treatment did not appear to block adaptive host immune responses.Conclusions: Preclinical testing supports the safety and efficacy of a CD27-containing CAR targeting CD70-expressing tumors. Clin Cancer Res; 23(9); 2267–76. ©2016 AACR.
TERT Promoter Mutations Enhance Telomerase Activation by Long-Range Chromatin Interactions
Authors: Min Jaewon , Shay Jerry W. 
Published: November 2016

Abstract
Summary: Although single-nucleotide somatic mutations in the proximal promoter of the human telomerase reverse transcriptase (TERT) gene create novel consensus sequences for transcription factors that enhance TERT expression, the precise mechanism of how telomerase is reactivated in cancer cells remains poorly understood. In this issue, Akıncılar and colleagues identify a potential mechanism of TERT reactivation that is mediated by a novel long-range chromatin interaction between the TERT promoter on chromosome 5p and a 300-kb upstream region. This permits recruitment of the transcription factor GABPA in mutant TERT promoters but not in wild-type promoters. Cancer Discov; 6(11); 1212–4. ©2016 AACR.
See related article by Akıncılar and colleagues, p. 1276.
Rescue of Tolerant CD8+ T Cells during Cancer Immunotherapy with IL2:Antibody Complexes
Authors: Klevorn Lauryn E. , Berrien-Elliott Melissa M. , Yuan Jinyun , Kuehm Lindsey M. , Felock Gregory D. , Crowe Sean A. , Teague Ryan M. 
Published: November 2016

AbstractInterleukin-2 (IL2) was among the earliest reagents used for cancer immunotherapy due to its ability to support the survival and function of tumor-reactive T cells. However, treatment with IL2 is accompanied by off-target toxicity and low response rates in patients. In mouse models, these issues are largely overcome when IL2 is administered as a cytokine/antibody complex (IL2c). The complex has a longer serum half-life and can be designed for preferential cytokine delivery to specific cells of interest. Early studies showed IL2c could boost antitumor immunity in mice by activating tumor-reactive CD8+ T cells. But such functional T cells are often limited in the tumor microenvironment, where instead unresponsive tolerant T cells are eventually eliminated by apoptosis, representing a major obstacle to the success of cancer immunotherapy. We found that IL2c treatment rescued tumor-specific CD8+ T cells from a state of established tolerance, providing effective immunotherapy in tumor-bearing mice. Expression of the transcription factor T-bet was necessary to drive intratumoral IFNγ production and effector activity by T cells rescued with IL2c. Furthermore, IL2c promoted T-bet expression in human CD4+ and CD8+ T cells in humanized tumor-bearing mice, but also increased the frequency of Foxp3+ regulatory T cells. Our study reveals a novel role for IL2c as a powerful immunotherapeutic reagent capable of reversing tolerance in tumor-reactive T cells, and provides the first evidence that IL2c influences human T cells in vivo, highlighting the translational potential to modulate human antitumor immune responses. Cancer Immunol Res; 4(12); 1016–26. ©2016 AACR.
Functional Assessment of Coronary Artery Disease in Patients Undergoing Transcatheter Aortic Valve Implantation
Authors: Pesarini Gabriele , Scarsini Roberto , Zivelonghi Carlo , Piccoli Anna , Gambaro Alessia , Gottin Leonardo , Rossi Andrea , Ferrero Valeria , Vassanelli Corrado , Ribichini Flavio 
Published: November 2016

Background—
Aortic valve stenosis may influence fractional flow reserve (FFR) of concomitant coronary artery disease by causing hypertrophy and reducing the vasodilatory reserve of the coronary circulation. We sought to investigate whether FFR values might change after valve replacement.

Methods and Results—

The functional relevance of 133 coronary lesions was assessed by FFR in 54 patients with severe aortic valve stenosis before and after transcatheter aortic valve implantation (TAVI) during the same procedure. A linear mixed model was used to verify the interaction of TAVI effect with the FFR values. No significant overall change in FFR values was found before and after the aortic valve stenosis removal (0.89±0.10 versus 0.89±0.13;
P
=0.73). A different trend in FFR groups (positive if ≤0.8; negative if >0.8) was found after TAVI (
P
for interaction <0.001). Positive FFR values worsened after TAVI (0.71±0.11 versus 0.66±0.14). Conversely, negative FFR values improved after TAVI (0.92±0.06 versus 0.93±0.07). Similarly, FFR values in coronary arteries with lesions presenting percent diameter stenosis >50 worsened after TAVI (0.84±0.12 versus 0.82±0.16;
P
=0.02), whereas FFR values in arteries with mild lesions (percent diameter stenosis <50) tended toward improvement after TAVI (0.90±0.07 versus 0.91±0.09;
P
=0.69). Functional FFR variations after TAVI changed the indication to treat the coronary stenosis in 8 of 133 (6%) lesions.

Conclusions—
Coronary hemodynamics are influenced by aortic valve stenosis removal. Nevertheless, FFR variations after TAVI are minor and crossed the diagnostic cutoff of 0.8 in a small number of patients after valve replacement. Borderline coronary lesions might become functionally significant after valve replacement, although FFR-guided interventions were infrequent even in patients with angiographically significant lesions.
Insulin-Like Growth Factor 1 Receptor-Dependent Pathway Drives Epicardial Adipose Tissue Formation After Myocardial Injury
Authors: Zangi Lior , Oliveira Marcela S. , Ye Lillian Y. , Ma Qing , Sultana Nishat , Hadas Yoav , Chepurko Elena , Später Daniela , Zhou Bin , Chew Wei Leong , Ebina Wataru , Abrial Maryline , Wang Qing-Dong , Pu William T. , Chien Kenneth R. 
Published: November 2016

Background:
Epicardial adipose tissue volume and coronary artery disease are strongly associated, even after accounting for overall body mass. Despite its pathophysiological significance, the origin and paracrine signaling pathways that regulate epicardial adipose tissue’s formation and expansion are unclear.

Methods:
We used a novel modified mRNA-based screening approach to probe the effect of individual paracrine factors on epicardial progenitors in the adult heart.

Results:

Using 2 independent lineage-tracing strategies in murine models, we show that cells originating from the Wt1
+
mesothelial lineage, which includes epicardial cells, differentiate into epicardial adipose tissue after myocardial infarction. This differentiation process required Wt1 expression in this lineage and was stimulated by insulin-like growth factor 1 receptor (IGF1R) activation. IGF1R inhibition within this lineage significantly reduced its adipogenic differentiation in the context of exogenous, IGF1-modified mRNA stimulation. Moreover, IGF1R inhibition significantly reduced Wt1 lineage cell differentiation into adipocytes after myocardial infarction.

Conclusions:

Our results establish IGF1R signaling as a key pathway that governs epicardial adipose tissue formation in the context of myocardial injury by redirecting the fate of Wt1
+
lineage cells. Our study also demonstrates the power of modified mRNA -based paracrine factor library screening to dissect signaling pathways that govern progenitor cell activity in homeostasis and disease.
Robust Identification of Local Biogeophysical Effects of Land-Cover Change in a Global Climate Model
Authors: Winckler J. , Reick C. H. , Pongratz J. 
Published: November 2016

Abstract
Land-cover change (LCC) happens locally. However, in almost all simulation studies assessing biogeophysical climate effects of LCC, local effects (due to alterations in a model grid box) are mingled with nonlocal effects (due to changes in wide-ranging climate circulation). This study presents a method to robustly identify local effects by changing land surface properties in selected “LCC boxes” (where local plus nonlocal effects are present), while leaving others unchanged (where only nonlocal effects are present). While this study focuses on the climate effects of LCC, the method presented here is applicable to any land surface process that is acting locally but is capable of influencing wide-ranging climate when applied on a larger scale. Concerning LCC, the method is more widely applicable than methods used in earlier studies. The study illustrates the possibility of validating simulated local effects by comparison to observations on a global scale and contrasts the underlying mechanisms of local and nonlocal effects. In the MPI-ESM, the change in background climate induced by extensive deforestation is not strong enough to influence the local effects substantially, at least as long as sea surface temperatures are not affected. Accordingly, the local effects within a grid box are largely independent of the number of LCC boxes in the isolation approach.