bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Model-Based Cost-Effectiveness Analysis of an Exercise Program for Lung Cancer Survivors Following Curative-Intent Treatment
Authors: Ha Duc , Kerr Jacqueline , Ries Andrew L. , Fuster Mark M. , Lippman Scott M. , Murphy James D. 
Published: February 2019

AbstractRationaleThe Institute of Medicine emphasizes care in the post-treatment phase of the cancer survivorship continuum. Physical exercise has been shown to be effective in improving physical function and quality of life in cancer survivors; however, its cost-effectiveness in lung cancer survivors is not well established.ObjectiveWe performed a model-based cost-effectiveness analysis of an exercise intervention in lung cancer survivors following curative-intent treatment.MethodsWe constructed a Markov model to simulate the impact of the Lifestyle Interventions and Independence for Elders (LIFE) exercise intervention compared to usual care for stage I-IIIA lung cancer survivors. Costs and utility benefit of exercise were extracted from the LIFE study. Baseline utilities, transition probabilities, and survival were modeled. We calculated and considered incremental cost-effectiveness ratios (ICERs) <$100,000/quality-adjusted life-year (QALY) as cost-effective, and assessed model uncertainty using one-way and probabilistic sensitivity analyses.ResultsOur base-case model found that the LIFE exercise program would increase overall cost by $4,740 and effectiveness by 0.06 QALYs compared to usual care, and have an ICER of $79,504/QALY. The model was most sensitive to the cost of the exercise program, probability of increasing exercise, and utility benefit related to exercise. At a willingness-to-pay threshold of $100,000/QALY, the LIFE exercise program had a 71% probability of being cost-effective compared to 27% for usual care. When we included opportunity costs, the LIFE exercise program had an ICER of $179,774/QALY, exceeding the cost-effectiveness threshold.ConclusionsA simulation of the LIFE exercise program in lung cancer survivors following curative-intent treatment demonstrates cost-effectiveness from an organization but not societal perspective. Strategies to effectively increase exercise remotely may be more cost-effective than in-facility strategies for these patients.
Detection of malaria in insectary-reared Anopheles gambiae using near-infrared spectroscopy
Authors: Maia Marta F. , Kapulu Melissa , Muthui Michelle , Wagah Martin G. , Ferguson Heather M. , Dowell Floyd E. , Baldini Francesco , Cartwright Lisa-Ranford 
Published: February 2019

AbstractLarge-scale surveillance of mosquito populations is crucial to assess the intensity of vector-borne disease transmission and the impact of control interventions. However, there is a lack of accurate, cost-effective and high-throughput tools for mass-screening of vectors. This study demonstrates proof-of-concept that near-infrared spectroscopy (NIRS) is capable of rapidly identifying laboratory strains of human malaria infection in African mosquito vectors. By using partial least square regression models based on malaria-infected and uninfected Anopheles gambiae mosquitoes, we showed that NIRS can detect oocyst- and sporozoite-stage Plasmodium falciparum infections with 88% and 95% accuracy, respectively. Accurate, low-cost, reagent-free screening of mosquito populations enabled by NIRS could revolutionize surveillance and elimination strategies for the most important human malaria parasite in its primary African vector species. Further research is needed to evaluate how the method performs in the field following adjustments in the training datasets to include data from wild-caught infected and uninfected mosquitoes.
Evolutionary dynamics of neoantigens in growing tumours
Authors: Lakatos Eszter , Williams Marc J. , Schenck Ryan O. , Cross William C. H. , Househam Jacob , Werner Benjamin , Gatenbee Chandler , Robertson-Tessi Mark , Barnes Chris P. , Anderson Alexander R. A. , Sottoriva Andrea , Graham Trevor A. 
Published: February 2019

ABSTRACTCancer evolution is driven by the acquisition of somatic mutations that provide cells with a beneficial phenotype in a changing microenvironment. However, mutations that give rise to neoantigens, novel cancer–specific peptides that elicit an immune response, are likely to be disadvantageous. Here we show how the clonal structure and immunogenotype of growing tumours is shaped by negative selection in response to neoantigenic mutations. We construct a mathematical model of neoantigen evolution in a growing tumour, and verify the model using genomic sequencing data. The model predicts that, in the absence of active immune escape mechanisms, tumours either evolve clonal neoantigens (antigen– ‘hot’), or have no clonally– expanded neoantigens at all (antigen– ‘cold’), whereas antigen– ‘warm’ tumours (with high frequency subclonal neoantigens) form only following the evolution of immune evasion. Counterintuitively, strong negative selection for neoantigens during tumour formation leads to an increased number of antigen– warm or – hot tumours, as a consequence of selective pressure for immune escape. Further, we show that the clone size distribution under negative selection is effectively– neutral, and moreover, that stronger negative selection paradoxically leads to more neutral– like dynamics. Analysis of antigen clone sizes and immune escape in colorectal cancer exome sequencing data confirms these results. Overall, we provide and verify a mathematical framework to understand the evolutionary dynamics and clonality of neoantigens in human cancers that may inform patient– specific immunotherapy decision– making.
Curriculum-based outdoor learning for children aged 9-11: A qualitative analysis of pupils’ and teachers’ views
Authors: Marchant Emily , Todd Charlotte , Cooksey Roxanne , Dredge Samuel , Jones Hope , Reynolds David , Stratton Gareth , Dwyer Russell , Lyons Ronan , Brophy Sinead 
Published: February 2019

AbstractThe relationship between child health, wellbeing and education demonstrates that healthier and happier children achieve higher educational attainment. An engaging curriculum that facilitates children in achieving their academic potential has strong implications for educational outcomes, future employment prospects and health and wellbeing during adulthood. Outdoor learning is a pedagogical approach used to enrich learning, enhance school engagement and improve pupil health and wellbeing. However, its non-traditional means of achieving curricular aims are not yet recognised beyond the early years by education inspectorates. This requires evidence into its acceptability from those at the forefront of delivery. This study aimed to explore headteachers’, teachers’ and pupils’ views and experiences of an outdoor learning programme within the key stage two curriculum (ages 9-11). We examine the process of implementation to offer case study evidence through 1:1 interviews with headteachers (n=3) and teachers (n=10) and focus groups with pupils aged 9-11 (n=10) from three primary schools. Interviews and focus groups were conducted at baseline and six months into implementation. Schools introduced regular outdoor learning within the curriculum. This study found a variety of perceived benefits for pupils and schools. Pupils and teachers noticed improvements in pupils’ engagement with learning, concentration and behaviour, as well as positive impacts on health and wellbeing and teachers’ job satisfaction. Curriculum demands including testing and evidencing work were barriers to implementation, in addition to safety concerns, resources and teacher confidence. Participants supported outdoor learning as a curriculum-based programme for older primary school pupils. However, embedding outdoor learning within the curriculum requires education inspectorates to place higher value on this approach in achieving curricular aims, alongside greater acknowledgment of the wider benefits to children which current measurements do not capture.
Cooperative population coding facilitates efficient sound source separability by adaptation to spatial statistics
Authors: Gleiss Helge , Encke Jörg , Lingner Andrea , Jennings Todd R. , Brosel Sonja , Kunz Lars , Grothe Benedikt , Pecka Michael 
Published: February 2019

AbstractOur sensory environment changes constantly. Accordingly, neural systems continually adapt to the concurrent stimulus statistics to remain sensitive over a wide range of conditions. Such dynamic range adaptation (DRA) is assumed to increase both the effectiveness of the neuronal code and perceptual sensitivity. However, direct demonstrations of DRA-based efficient neuronal processing that also produces perceptional benefits are lacking. Here we investigated the impact of DRA on spatial coding in the rodent brain and the perception of human listeners. Naturalistic spatial stimulation with dynamically changing source locations elicited prominent DRA already on the initial spatial processing stage, the Lateral Superior Olive (LSO) of gerbils of either sex. Surprisingly, on the level of individual neurons, DRA diminished spatial tuning due to large response variability across trials. However, when considering single-trial population averages of multiple neurons, DRA enhanced the coding efficiency specifically for the concurrently most probable source locations. Intrinsic LSO population imaging of energy consumption combined with pharmacology revealed that a slow-acting LSO gain control mechanism distributes activity across a group of neurons during DRA, thereby enhancing population coding efficiency. Strikingly, such “efficient cooperative coding” also improved neuronal source separability specifically for the locations that were most likely to occur. These location-specific enhancements in neuronal coding were paralleled by human listeners exhibiting a selective improvement in spatial resolution. We conclude that, contrary to canonical models of sensory encoding, the primary motive of early spatial processing is efficiency optimization of neural populations for enhanced source separability in the concurrent environment.Author summaryThe renowned efficient coding hypothesis suggests that neural systems adapt their processing to the statistics of the environment to maximize information while minimizing the underlying energetic costs. It is further assumed that such neuronal adaptations also confer perceptual advantages. Yet direct demonstrations of adaptive mechanisms or strategies that result both in increased neuronal coding efficiency and perceptual benefits are lacking. Here we show that an auditory spatial processing circuit exploits slow-acting gain control to distribute activity across the neuronal population, thereby enhancing coding efficiency based on single-trial population averages. This population-efficiency maximization also results in improved neuronal spatial resolution for the concurrently most probable source locations, which was resembled in a focally improved spatial acuity of human listeners.
Do damaging variants of SLC6A9, the gene for the glycine transporter 1 (GlyT-1), protect against schizophrenia?
Authors: Curtis David 
Published: February 2019

AimsTo test whether genetic variants predicted to impair the functionality of SLC6A9, which codes for the GlyT-1 glycine transporter, are protective against schizophrenia.MethodIn an exome sequenced sample of 4225 schizophrenia cases and 5834 controls variants occurring in SLC6A9 were annotated and weights were assigned using GENEVARASSOC. Genotype counts were compared using SCOREASSOC.ResultsVariants predicted to be deleterious by SIFT and damaging by PolyPhen were examined. Genotypes at 1:44466494-G/A seemed likely to be erroneous. If these were ignored then there were 15 damaging variants in controls and 5 in cases.ConclusionsThe results are consistent with the hypothesis that variants which damage SLC6A9 are protective against schizophrenia but a larger sample would be required to confirm this.Declaration of interestThe author declares no conflict of interest.
The scaling of expansive energy under the Red Queen predicts Cope’s Rule
Authors: Žliobaitė Indrė , Fortelius Mikael 
Published: February 2019

AbstractThe Red Queen’s hypothesis portrays evolution as a never-ending competition for expansive energy, where one species’ gain is another species’ loss. The Red Queen is neutral with respect to body size, implying that neither small nor large species have a universal competitive advantage. The maximum population growth in ecology; however, clearly depends on body size – the smaller the species, the shorter the generation length, and the faster it can expand. Here we ask whether, and if so how, the Red Queen’s hypothesis can accommodate a spectrum of body sizes. We theoretically analyse scaling of expansive energy with body mass and demonstrate that in the Red Queen’s zero-sum game for resources, neither small nor large species have a universal evolutionary advantage. We argue that smaller species have an evolutionary advantage only when resources in the environment are not fully occupied, such as after mass extinctions or following key innovations allowing expansion into freed up or previously unoccupied resource space. Under such circumstances, we claim, generation length is the main limiting factor for population growth. When competition for resources is weak, smaller species can indeed expand faster, but to sustain this growth they also need more resources. In the Red Queen’s realm, where resources are fully occupied and the only way for expansion is to outcompete other species, acquisition of expansive energy becomes the limiting factor and small species lose their physiological advantage. A gradual transition from unlimited resources to a zero-sum game offers a direct mechanistic explanation for observed body mass trends in the fossil record, known as Cope’s Rule. When the system is far from the limit of resources and competition is not maximally intense, small species take up ecological space faster. When the system approaches the limits of its carrying capacity and competition tightens, small species lose their evolutionary advantage and we observe a wider range of successful body masses, and, as a result, an increase in the average body mass within lineages.
A Polygenic Score for Body Mass Index is Associated with Depressive Symptoms via Early Life Stress: Evidence for gene-environment correlation
Authors: Avinun Reut , Hariri Ahmad R. 
Published: February 2019

ABSTRACTBackgroundIncreasing childhood overweight and obesity rates are associated with not only adverse physical, but also mental health outcomes, including depression. These negative outcomes may be caused and/or exacerbated by the bullying and shaming overweight individuals experience. As body mass index (BMI) can be highly heritable, we hypothesized that a genetic risk toward higher BMI, will predict higher early life stress (ELS), which in turn will predict higher depressive symptoms in adulthood. Such a process will reflect an evocative gene-environment correlation (rGE) wherein an individual’s genetically influenced phenotype evokes a reaction from the environment that subsequently shapes the individual’s health.MethodsWe modeled genetic risk using a polygenic score of BMI derived from a recent large GWAS meta-analysis. Self-reports were used for the assessment of ELS and depressive symptoms in adulthood. The discovery sample consisted of 524 non-Hispanic Caucasian university students from the Duke Neurogenetics Study (DNS; 278 women, mean age 19.78±1.23 years) and the independent replication sample consisted of 5 930 white British individuals from the UK biobank (UKB; 3 128 women, mean age 62.66±7.38 years).ResultsA significant mediation effect was found in the DNS (indirect effect=.207, bootstrapped SE=.10, 95% CI: .014 to .421), and then replicated in the UKB (indirect effect=.04, bootstrapped SE=.01, 95% CI: .018 to .066). Higher BMI polygenic scores were associated with higher depressive symptoms through the experience of higher ELS.ConclusionsOur findings suggest that evocative rGE may contribute to weight-related mental health problems and stress the need for interventions that aim to reduce weight bias, specifically during childhood.
Cortical tracking of speech reveals top-down reconstructive processes
Authors: Mukherjee Sankar , Tomassini Alice , Badino Leonardo , Pastore Aldo , Fadiga Luciano , D’Ausilio Alessandro 
Published: February 2019

AbstractCortical entrainment to the (quasi-) rhythmic components of speech seems to play an important role in speech comprehension. It has been suggested that neural entrainment may reflect top-down temporal predictions of sensory signals. Key properties of a predictive model are its anticipatory nature and its ability to reconstruct missing information. Here we put both these two properties to experimental test. We acoustically presented sentences and measured cortical entrainment to both acoustic speech envelope and lips kinematics acquired from the speaker but not visible to the participants. We then analyzed speech-brain and lips-brain coherence at multiple negative and positive lags. Besides the well-known cortical entrainment to the acoustic speech envelope, we found significant entrainment in the delta range to the (latent) lips kinematics. Most interestingly, the two entrainment phenomena were temporally dissociated. While entrainment to the acoustic speech peaked around +0.3 s lag (i.e., when EEG followed speech by 0.3 s), entrainment to the lips was significantly anticipated and peaked around 0-0.1 s lag (i.e., when EEG was virtually synchronous to the putative lips movement). Our results demonstrate that neural entrainment during speech listening involves the anticipatory reconstruction of missing information related to lips movement production, indicating its fundamentally predictive nature and thus supporting analysis by synthesis models.
The genomic architecture of competitive response of Arabidopsis thaliana is highly flexible between monospecific and plurispecific neighborhoods
Authors: Libourel Cyril , Baron Etienne , Lenglet Juliana , Amsellem Laurent , Roby Dominique , Roux Fabrice 
Published: February 2019

AbstractAlthough plants simultaneously interact with multiple neighboring species throughout their life cycle, there is still very limited information about the genetics of the competitive response in the context of plurispecific interactions. Using a local mapping population of Arabidopsis thaliana, we set up a Genome Wide Association study to estimate the extent of genetic variation of the competitive response in presence of 12 plant species assemblages, and to compare the genetic architecture of the competitive response between monospecific and plurispecific neighborhoods. Based on four phenotypic traits, we detected strong crossing reaction norms not only among the three monospecific neighborhoods, but also among the different plant assemblages. Accordingly, the genetic architecture of the competitive response was highly dependent on the identity and the relative abundance of the neighboring species. In addition, enriched biological processes underlying the competitive response largely differ between monospecific and plurispecific neighborhoods. In particular, receptor-like kinases and transporters were significantly enriched in plurispecific neighborhoods. Our results suggest that plants can integrate and respond to different species assemblages depending on the identity and number of each neighboring species, through a large range of genes associated mainly with perception and signaling processes leading to developmental and stress responses.
A human photoacoustic imaging reporter gene using the clinical dye indocyanine green
Authors: Nyström Nivin N. , Yip Lawrence C.M. , Carson Jeffrey J.L. , Scholl Timothy J. , Ronald John A. 
Published: February 2019

ABSTRACTPhotoacoustic imaging (PAI) combines optical contrast with the resolution and depth-detection of ultrasound and is increasingly being utilized for medical imaging in patients. PAI reporter genes would allow for monitoring of cell and gene therapies, but current reporters have immunogenicity and/or toxicity concerns that may limit clinical translation. Here we report a PAI reporter system employing the ability of humanorganic anion transporting polypeptide 1b3(Oatp1b3) to take up the clinical dye indocyanine green (ICG) into cells. Following ICG administration, cells synthetically expressingOatp1b3exhibited significantly increased PAI signals compared to control cells bothin vitroand in mice. Several benefits of this technology are the human derivation ofOatp1b3, and the high extinction coefficient, low quantum yield and pre-existing clinical approval of ICG. We posit that theOatp1b3-ICG reporter system could be useful forin vivogene and cell tracking in preclinical and clinical applications.
Increasing Synaptic GluN2B levels within the Basal and Lateral Amygdala Enables the Modification of Strong Reconsolidation Resistant Fear Memories
Authors: Solis Christopher A. de , Gonzalez Cuauhtémoc U. , Galdamez Mario A. , Perish John M. , Woodard Samuel W. , Salinas Carlos E. , Miller Joel N. , Elahi Hajira , Pineda Oziel H. , Oad Shayrin , las Fuentes Serafin Gatica de , Owen Malissa S. , Sandoval Alfredo , Holehonnur Roopashri , Ploski Jonathan E. 
Published: February 2019

AbstractReconsolidation disruption has been proposed as a method to attenuate pathological memories in disorders such as PTSD. However, studies from our group and others indicate that strong memories are resistant to becoming destabilized following reactivation, rendering them impervious to agents that disrupt the re-stabilization phase of reconsolidation. Thus, therapies designed to attenuate maladaptive memories by disrupting reconsolidation updating have not been adequately developed. We previously determined that animals possessing strong auditory fear memories, compared to animals with weaker fear memories, are associated with an enduring increase in the synaptic GluN2A/GluN2B ratio in neurons of the mouse basal and lateral amygdala (BLA). In this study, we determined whether increasing GluN2B levels within BLA excitatory neuronal synapses is sufficient to enable modification of strong fear memories via reconsolidation. To accomplish this, we utilized a combinatorial genetic strategy to express GluN2B or GluN2B(E1479Q) in excitatory neurons of the mouse BLA before or after fear memory consolidation. GluN2B(E1479Q) contains a point mutation that increases synaptic expression of the subunit by interfering with phosphorylation-driven endocytosis. At the time of memory retrieval, increasing synaptic GluN2B levels by expression of GluN2B(E1479Q), butnotGluN2B(WT), enhanced the induction of reconsolidation rendering the strong fear memory modifiable. GluN2B(WT) or GluN2B(E1479Q) expression did not influence fear memory maintenance or extinction. Fear memory consolidation, however, was enhanced when GluN2B(E1479Q) was expressed in the BLA at the time of training. These findings indicate that enhancing GluN2B synaptic trafficking may provide a novel therapeutic strategy to enhance modification of pathological memories.