bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial tuning shifts increase the discriminability and fidelity of population codes in visual cortex
Authors: Vo Vy A. , Sprague Thomas C. , Serences John T. 
Published: November 2016

ABSTRACTSelective visual attention enables organisms to enhance the representation of behaviorally relevant stimuli by altering the encoding properties of single receptive fields (RFs). Yet we know little about how the attentional modulations of single RFs contribute to the encoding of an entire visual scene. Addressing this issue requires (1) measuring a group of RFs that tile a continuous portion of visual space, (2) constructing a population-level measurement of spatial representations based on these RFs, and (3) linking how different types of RF attentional modulations change the population-level representation. To accomplish these aims, we used fMRI to characterize the responses of thousands of voxels in retinotopically organized human cortex. First, we found that the response modulations of voxel RFs (vRFs) depend on the spatial relationship between the RF center and the visual location of the attended target. Second, we used two analyses to assess the spatial encoding quality of a population of voxels. We found that attention increased fine spatial discriminability and representational fidelity near the attended target. Third, we linked these findings by manipulating the observed vRF attentional modulations and recomputing our measures of the fidelity of population codes. Surprisingly, we discovered that attentional enhancements of population-level representations largely depend on position shifts of vRFs, rather than changes in size or gain. Our data suggest that position shifts of single RFs are a principal mechanism by which attention enhances population-level representations in visual cortex.SIGNIFICANCE STATEMENTWhile changes in the gain and size of RFs have dominated our view of how attention modulates information codes of visual space, such hypotheses have largely relied on the extrapolation of single-cell responses to population responses. Here we use fMRI to relate changes in single voxel receptive fields (vRFs) to changes in the precision of representations based on larger populations of voxels. We find that vRF position shifts contribute more to population-level enhancements of visual information than changes in vRF size or gain. This finding suggests that position shifts are a principal mechanism by which spatial attention enhances population codes for relevant visual information in sensory cortex. This poses challenges for labeled line theories of information processing, suggesting that downstream regions likely rely on distributed inputs rather than single neuron-to-neuron mappings.
Antidepressant-like effects of P2 purinergic antagonist PPADS is dependent on serotonergic and noradrenergic integrity
Authors: Diniz Cassiano R. A. F. , Rodrigues Murilo , Casarotto Plínio C. , Pereira Vítor S. , Crestani Carlos C. , Joca Sâmia R. L. 
Published: November 2016

AbstractDepression is a common mental disorder affecting around 350 million of individuals globally. The available antidepressant drug monotherapy is far from ideal since it has an efficiency of approximately 60% and takes around 3-4 week to achieve clinical improvement. Attention has been paid to the purinergic signaling regarding neuropathological mechanisms, since it might be involved in psychiatric disorders, such as depression. In fact, blockade of purinergic P2X receptors induces antidepressant-like effects in preclinical models. However, the mechanisms involved in this effect are not yet completely understood. The present work investigated the interplay between a P2X receptor antagonist (PPADS) and clinically used antidepressant drugs on the forced swimming test, an animal model predictive of antidepressant effect. We observed significant synergistic effect of PPADS combined with sub-effective doses of fluoxetine or reboxetine in the FST. Moreover, depletion of serotonergic or noradrenergic systems, with PCPA and DSP-4 treatment, respectively, blocked the antidepressant-like effect of PPADS. No increase in locomotion, a possible source of confusion on FST data, was detected in any of the treated groups. Our results indicate the antidepressant-like effect of PPADS depends on the integrity of serotonergic and noradrenergic transmission.
Recent progress in multi-electrode spike sorting methods
Authors: Lefebvre Baptiste , Yger Pierre , Marre Olivier 
Published: November 2016

AbstractIn recent years, arrays of extracellular electrodes have been developed and manufactured to record simultaneously from hundreds of electrodes packed with a high density. These recordings should allow neuroscientists to reconstruct the individual activity of the neurons spiking in the vicinity of these electrodes, with the help of signal processing algorithms. Algorithms need to solve a source separation problem, also known as spike sorting. However, these new devices challenge the classical way to do spike sorting. Here we review different methods that have been developed to sort spikes from these large-scale recordings. We describe the common properties of these algorithms, as well as their main differences. Finally, we outline the issues that remain to be solved by future spike sorting algorithms.
TheNDE1genomic locus can affect treatment of psychiatric illness through gene expression changes related to MicroRNA-484
Authors: Bradshaw Nicholas J. , Ukkola-Vuoti Liisa , Pankakoski Maiju , Zheutlin Amanda B. , Ortega-Alonso Alfredo , Torniainen-Holm Minna , Sinha Vishal , Therman Sebastian , Paunio Tiina , Suvisaari Jaana , Lönnqvist Jouko , Cannon Tyrone D. , Haukka Jari , Hennah William 
Published: November 2016

AbstractGenetic studies of familial schizophrenia in Finland have observed significant associations with a group of biologically related genes,DISC1, NDE1, NDEL1,PDE4BandPDE4D,the “DISC1 network”. Here, we utilize gene expression and psychoactive medication use data to study their biological consequences and potential treatment implications. Gene expression levels were determined in 64 individuals from 18 families, whilst prescription medication information has been collected over a ten-year period for 931 affected individuals. We demonstrate that theNDE1SNP rs2242549 associates with significant changes in gene expression for 2,908 probes (2,542 genes), of which 794 probes (719 genes) were replicable. A significant number of the genes altered were predicted targets of microRNA-484 (p=3.0×10−8), located on a non-coding exon ofNDE1.Variants within theNDE1locus also displayed significant genotype by gender interaction to early cessation of psychoactive medications metabolized by CYP2C19. Furthermore, we demonstrate that miR-484 can affect the expression ofCYP2C19in a cell culture system. Thus, variation at theNDE1locus may alter risk of mental illness, in part through modification of miR-484, and such modification alters treatment response to specific psychoactive medications, leading to the potential for use of this locus in targeting treatment.
Interpreting deep mutational scanning data resulting from selections on solid media
Authors: Klesmith Justin R. , Thorwall Sarah , Whitehead Timothy A. 
Published: November 2016

AbstractDeep mutational scanning is now used in directed evolution experiments to quantify the change in frequency of a cellular variant in a mixed population. A key concern is the extent to which the enrichment of a variant in a population corresponds to a fitness metric like relative growth rate or survival percentage. We present here analytical equations converting the enrichment of a variant to fitness metrics for plate-based selections. Using isogenic and mixed cultures we show that growth rates and survival percentages correlate for antibiotic plate-based selections. These results are important for proper interpretation of data resulting from deep sequencing.
Genome-scale transcriptional regulatory network models for the mouse and human striatum predict roles for SMAD3 and other transcription factors in Huntington’s disease
Authors: Ament Seth A. , Pearl Jocelynn R. , Bragg Robert M. , Skene Peter J. , Coffey Sydney R. , Bergey Dani E. , Plaisier Christopher L. , Wheeler Vanessa C. , MacDonald Marcy E. , Baliga Nitin S. , Rosinski Jim , Hood Leroy E. , Carroll Jeffrey B. , Price Nathan D. 
Published: November 2016

AbstractTranscriptional changes occur presymptomatically and throughout Huntington’s Disease (HD), motivating the study of transcriptional regulatory networks (TRNs) in HD. We reconstructed a genome-scale model for the target genes of 718 TFs in the mouse striatum by integrating a model of the genomic binding sites with transcriptome profiling of striatal tissue from HD mouse models. We identified 48 differentially expressed TF-target gene modules associated with age‐ andHttallele-dependent gene expression changes in the mouse striatum, and replicated many of these associations in independent transcriptomic and proteomic datasets. Strikingly, many of these predicted target genes were also differentially expressed in striatal tissue from human disease. We experimentally validated a key model prediction that SMAD3 regulates HD-related gene expression changes using chromatin immunoprecipitation and deep sequencing (ChIP-seq) of mouse striatum. We foundHttallele-dependent changes in the genomic occupancy of SMAD3 and confirmed our model’s prediction that many SMAD3 target genes are down-regulated early in HD. Importantly, our study provides a mouse and human striatal-specific TRN and prioritizes a hierarchy of transcription factor drivers in HD.
Learning enhances sensory processing in mouse V1 before improving behavior
Authors: Jurjut Ovidiu , Georgieva Petya , Busse Laura , Katzner Steffen 
Published: November 2016

AbstractA fundamental property of visual cortex is to enhance the representation of those stimuli that are relevant for behavior, but it remains poorly understood how such enhanced representations arise during learning. Using classical conditioning in mice, we show that orientation discrimination is learned in a sequence of distinct behavioral stages, in which animals first rely on stimulus appearance before exploiting its orientation to guide behavior. After confirming that orientation discrimination under classical conditioning requires primary visual cortex (V1), we measured, during learning, response properties of V1 neurons. Learning improved neural discriminability, sharpened orientation tuning and led to higher contrast sensitivity. Remarkably, these learning-related improvements in the V1 representation were fully expressed before successful orientation discrimination was evident in the animals’ behavior. We propose that V1 plays a key role early in discrimination learning to enhance behaviorally relevant sensory information.
Evaluating Methods of Updating Training Data in Long-Term Genomewide Selection
Authors: Neyhart Jeffrey L. , Tiede Tyler , Lorenz Aaron J. , Smith Kevin P. 
Published: November 2016

ABSTRACTGenomewide selection is hailed for its ability to facilitate greater genetic gains per unit time. Over breeding cycles, the requisite linkage disequilibrium (LD) between quantitative trait loci (QTL) and markers is expected to change as a result of recombination, selection, and drift, leading to a decay in prediction accuracy. Previous research has identified the need to update the training population using data that may capture new LD generated over breeding cycles, however optimal methods of updating have not been explored. In a barley (Hordeum vulgareL.) breeding simulation experiment, we examined prediction accuracy and response to selection when updating the training population each cycle with the best predicted lines, the worst predicted lines, both the best and worst predicted lines, random lines, criterion-selected lines, or no lines. In the short-term, we found that updating with the best predicted lines or the best and worst predicted lines resulted in high prediction accuracy and genetic gain, but in the long-term, all methods (besides not updating) performed similarly. We also examined the impact of including all data in the training population or only the most recent data. Though patterns among update methods were similar, using a smaller, but more recent training population provided a slight advantage in prediction accuracy and genetic gain. In an actual breeding program, a breeder might desire to gather phenotypic data on lines predicted to be the best, perhaps to evaluate possible cultivars. Therefore, our results suggest that an optimal method of updating the training population is also very practical.
A functional genomic meta-analysis of clinical trials in systemic sclerosis: towards precision medicine and combination therapy
Authors: Taroni Jaclyn N. , Martyanov Viktor , Mahoney J. Matthew , Whitfield Michael L. 
Published: November 2016

ABSTRACTSystemic sclerosis (SSc) is an orphan, systemic autoimmune disease with no FDA-approved treatments. Its heterogeneity and rarity often result in underpowered clinical trials making the analysis and interpretation of associated molecular data challenging. We performed a meta-analysis of gene expression data from skin biopsies of SSc patients treated with five therapies: mycophenolate mofetil (MMF), rituximab, abatacept, nilotinib, and fresolimumab. A common clinical improvement criterion of -20% OR -5 modified Rodnan Skin Score was applied to each study. We developed a machine learning approach that captured features beyond differential expression that was better at identifying targets of therapies than the differential expression alone. Regardless of treatment mechanism, abrogation of inflammatory pathways accompanied clinical improvement in multiple studies suggesting that high expression of immune-related genes indicates active and targetable disease. Our framework allowed us to compare different trials and ask if patients who failed one therapy would likely improve on a different therapy, based on changes in gene expression. Genes with high expression at baseline in fresolimumab non-improvers were downregulated in MMF improvers, suggesting that immunomodulatory or combination therapy may have benefitted these patients. This approach can be broadly applied to increase tissue-specificity and sensitivity of differential expression results.
78Gy with Fiducial Marker Image‐Guided Radiotherapy in Prostate Cancer: Single Center Analysis of 301 Patients
Authors: Choong Ee Siang , Hruby George , Yang Jean , Kwong Carol , Patanjali Nitya 
Published: November 2016

AbstractAimIn prostate cancer, fiducial marker image‐guided radiotherapy (FMIGRT) allows correction of setup errors and interfraction physiological motion resulting in improved accuracy of target and sparing of at risk organs. We aim to report outcomes and toxicities observed in patients treated with dose escalation to 78Gy with FMIGRT in our center.Methods and MaterialsRetrospective review of consecutive patients with histologically confirmed T1‐4N0M0 localized prostate cancer treated with dose escalation to 78Gy with FMIGRT in our center. All patients had 3‐D conformal radiotherapy. Duration of androgen deprivation therapy use was tailored to risk group. Toxicity was scored according to CTCAE.v04. Kaplan–Meier analysis was performed for freedom from biochemical failure (FFBF), prostate cancer‐specific survival and overall survival.ResultsMedian follow‐up was 48.6 months. Median duration of androgen deprivation therapy was 6 and 23 months in the intermediate‐ and high‐risk group, respectively. FFBF at 5 years was 88.8%. FFBFs when stratified to risk groups were 100% for low risk, 88.9% for low‐intermediate risk, 89.9% for high‐intermediate risk and 85.4% for high risk, respectively. Acute severe toxicity (grade≥3) rate for both genitourinary (GU) and gastrointestinal (GI) was 1%. Late moderate‐to‐severe toxicity (grade≥2) rates for GU and GI were 15% and 17%, respectively, with severe (grade≥3) toxicity rate for GU and GI at 2% and 3%, respectively.ConclusionDose escalation to 78Gy with FMIGRT in our series achieved good FFBF at 5 years with low acute and late toxicity rates. These results provide a good comparator cohort to our current use of image‐guided intensity modulated radiotherapy.
Every three‐hour versus every six‐hour oral feeding in preterm infants: a randomised clinical trial
Authors: Gray Megan M. , Medoff‐Cooper Barbara , Enlow Elizabeth M. , Mukhopadhyay Sagori , DeMauro Sara B. 
Published: November 2016

AbstractAimThis trial compares two oral feeding schedules, every three‐hour and every six‐hour oral feeding attempts, to determine which schedule allows for more rapid attainment of full oral feeding in preterm infants.MethodsInfants born at ≤33‐week gestation were randomly assigned to receive oral feeding every three hours or every six hours if feeding cues were present. The primary outcome was time to full oral feeding; secondary outcomes include respiratory and apnoea rates, growth and length of stay.ResultsA total of 55 infants were recruited. There was no difference between the groups in the primary or secondary outcomes.ConclusionFor preterm infants fed when oral feeding cues are present, an every six‐hour schedule did not alter the time to full oral feeding and had no effect on rates of tachypnoea, apnoea or length of hospital stay compared to every three‐hour feeding schedule. An every six‐hour oral feeding schedule led to only small reductions in number of oral feeding attempts per day.
Scoping review shows wide variation in the definitions of bronchopulmonary dysplasia in preterm infants and calls for a consensus
Authors: Hines Delaney , Modi Neena , Lee Shoo K. , Isayama Tetsuya , Sjörs Gunnar , Gagliardi Luigi , Lehtonen Liisa , Vento Maximo , Kusuda Satoshi , Bassler Dirk , Mori Rintaro , Reichman Brian , Håkansson Stellan , Darlow Brian A. , Adams Mark , Rusconi Franca , San Feliciano Laura , Lui Kei , Morisaki Naho , Musrap Natasha , Shah Prakesh S. ,   the International Network for Evaluating Outcomes (iNeo) of Neonates
Published: November 2016

AbstractThe use of different definitions for bronchopulmonary dysplasia (BPD) has been an ongoing challenge. We searched papers published in English from 2010 and 2015 reporting BPD as an outcome, together with studies that compared BPD definitions between 1978 and 2015. We found that the incidence of BPD ranged from 6% to 57%, depending on the definition chosen, and that studies that investigated correlations with long‐term pulmonary and/or neurosensory outcomes reported moderate‐to‐low predictive values regardless of the BPD criteria.ConclusionA comprehensive and evidence‐based definition for BPD needs to be developed for benchmarking and prognostic use.
Reintroduction failure is common among adolescents after double‐blind placebo‐controlled food challenges
Authors: Strinnholm Å , Winberg A , Hedman L , Rönmark E , Lindh V 
Published: November 2016

AbstractAimThere has been a lack of research on adolescents who undergo double‐blind placebo‐controlled food challenges. The aim of this study was to investigate food allergic adolescents' experiences and consequences of double‐blind placebo‐controlled food challenges.MethodsThis qualitative, descriptive interview study included 17 adolescents aged 14–15 years with total elimination of cows' milk, hens' eggs or cod due to food allergies. The participants, who were initially identified from a large population‐based cohort study, were interviewed 18 months after completing their challenges.ResultsThe double‐blind placebo‐controlled food challenge proved to be a complex experience for the adolescents, involving fear of potential reactions and the hope that the food could be reintroduced. Experiences during the challenge were described in three themes: facing fears in a secure environment, being hesitant but curious about unknown tastes and waiting for unknown food reactions. Experiences after the challenge were described in two themes: gaining control and freedom and continuing old habits. A negative challenge was not consistently associated with the reintroduction of the challenged food.ConclusionThis study highlighted the importance of considering the adolescents' expectations and experiences of the challenge and the reintroduction process to ensure desirable changes in their dietary habits. Follow‐ups should be performed regardless of the outcome of challenges.
Clinical utility of next‐generation sequencing‐based minimal residual disease in paediatric B‐cell acute lymphoblastic leukaemia
Authors: Sekiya Yuko , Xu Yinyan , Muramatsu Hideki , Okuno Yusuke , Narita Atsushi , Suzuki Kyogo , Wang Xinan , Kawashima Nozomu , Sakaguchi Hirotoshi , Yoshida Nao , Hama Asahito , Takahashi Yoshiyuki , Kato Koji , Kojima Seiji 
Published: November 2016

SummaryWe assessed the clinical utility of next‐generation sequencing (NGS)‐based monitoring of minimal residual disease (MRD) in a uniformly treated cohort of 79 patients with paediatric B‐cell acute lymphoblastic leukaemia. Bone marrow samples were collected at the time of diagnosis, days 33 and 80, pre‐ (4–5 months) and post‐ (24 months) maintenance therapy time points, and at relapse. We identified leukaemia‐specific CDR3 sequences in 72 of 79 patients (91%) and detected MRD in 59 of 232 samples. Although MRD was detected in 28 of 55 samples (51%) on day 33, the frequencies of MRD detection decreased to 25% (16/65) at day 80, 19% (11/58) at 4–5 months and 7·4% (4/54) at 24 months. In a univariate analysis, positive MRD results on day 80 [relative risk (RR) 95% confidence interval (CI) = 7·438 (2·561–21·6), P < 0·001], at 4–5 months [RR (95% CI) = 10·24 (3·374–31·06), P < 0·001], and at 24 months [RR (95% CI) = 19·26 (4·974–74·59), P < 0·001] exhibited statistically significant associations with inferior leukaemia‐free survival; this was confirmed using a Cox proportional hazard model. Our study suggests the promising potential of NGS‐MRD for patients with B‐cell ALL.