bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Normative Study of Objective Measures of Disparity Vergence and Saccades in Children 9 to 17 Years Old
Authors: Namaeh Mashael , Scheiman Mitchell M. , Yaramothu Chang , Alvarez Tara L. 
Published: June 2020

SIGNIFICANCE
This study establishes normative data for objective outcome measures of vergence and saccade eye movements for the pediatric population. These data should facilitate future clinical trial design.

PURPOSE
This study was designed to establish normative data for objective measures of disparity vergence and saccades in children between the ages 9 and 17 years using an objective binocular eye movement tracking system.

METHODS
Participants (aged 9 to 17 years) had a vision examination including refraction, accommodative, and binocular vision testing. Eligibility criteria included 20/25 visual acuity with best correction, normal accommodation, and binocular vision. The ISCAN RK-826PCI binocular tracking system (ISCAN, Woburn, MA) was used to objectively record horizontal, symmetrical disparity vergence, and saccadic eye movements. Parameters assessed included peak velocity, time to peak velocity, latency, and response amplitude for both disparity vergence and saccades.

RESULTS
One hundred eighteen participants were recruited (54.94% female; mean age, 13.5 years), and 77.1% (91/118) of the participants completed the assessment with usable data. A sample of the normative data included peak velocity (°/s), which had a mean ± standard deviation of 25.4 ± 2.9, 22.0 ± 3.0, 225 ± 16.7, and 332.5 ± 20.5 for 4° convergence, 4° divergence, 5° saccades, and 10° saccades, respectively. The mean ± standard deviation for the latency (seconds) measures were 0.28 ± 0.1, 0.28 ± 0.16, 0.23 ± 0.05, and 0.23 ± 0.05 for 4° convergence, 4° divergence, 5° saccades, and 10° saccades, respectively.

CONCLUSIONS
Normative data enable researchers to have benchmark results for comparison with patient populations with binocular dysfunction. These objective disparity vergence measures can serve as outcome measures in future clinical trials to assess the effectiveness of therapeutic interventions by determining whether post-treatment results are similar to normal data.
Longitudinal Evaluation of the Structural and Functional Changes Associated with Glaucoma in Myopia
Authors: Biswas Sayantan , Biswas Partha 
Published: June 2020

SIGNIFICANCE
This study ascertains that myopia is a risk factor for glaucoma progression among eyes with primary open angle glaucoma. Myopic eyes with primary open angle glaucoma may benefit from measurement and incorporation of axial length information into clinical decision making.

PURPOSE
The purpose of this study was to estimate the rate of change in retinal nerve fiber layer (RNFL) thickness and the rate of change in visual field of glaucoma patients with and without myopia.

METHODS
We conducted a prospective, observational cohort study where we analyzed 245 eyes of 135 glaucoma patients followed for a mean period of 6.08 years. All the subjects had RNFL imaging and standard automated perimetry performed for both eyes in the same visit every 4 months for at least 60 months.

RESULTS
The rate of change of average RNFL thickness and visual field index (VFI) was −0.29 μm/y (95% confidence interval, −1.80 to +1.23 μm/y) and −0.30%/y (95% confidence interval, −2.24 to +1.64%/y), respectively, after adjusting for age, axial length, IOP, baseline RNFL thickness, signal strength, and correlation between fellow eyes. Axial length, as a continuous variable, was not associated with the rates of change of average RNFL thickness and VFI. However, high myopic eyes with axial lengths of ≥26.0 and ≥26.5 mm had an average rate of change of RNFL thickness of 0.15 and 0.16 μm/y faster than eyes with axial lengths of less than 26 and 26.5 mm, respectively. Similarly, myopic eyes with an axial length of ≥26.5 mm were associated with a 0.21%/y faster rate of VFI reduction.

CONCLUSIONS
Both RNFL and visual field progression rates are faster in myopic glaucomatous eyes with an axial length of ≥26.5 mm than in eyes <26.5 mm. However, the small difference that supports high myopia as a risk factor for progression does not indicate the clinical importance or significance of axial length.
Human Induced Pluripotent Stem Cell Derived Sensory Neurons are Sensitive to the Neurotoxic Effects of Paclitaxel
Authors: Xiong Chenling , Chua Katherina C. , Stage Tore B. , Kim Jeffrey , Altman-Merino Anne , Chan Daniel , Saraf Krishna , Ferracini Amanda Canato , Fattahi Faranak , Kroetz Deanna L. 
Published: June 2020

AbstractChemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting adverse event associated with treatment with paclitaxel and other chemotherapeutic agents. The prevention and treatment of CIPN are limited by a lack of understanding of the molecular mechanisms underlying this toxicity. In the current study, a human induced pluripotent stem cell–derived sensory neuron (iPSC-SN) model was developed for the study of chemotherapy-induced neurotoxicity. The iPSC-SNs express proteins characteristic of nociceptor, mechanoreceptor and proprioceptor sensory neurons and show Ca2+influx in response to capsaicin, α,β-meATP and glutamate. iPSC-SNs are relatively resistant to the cytotoxic effects of paclitaxel, with IC50values of 38.1 μM (95% CI: 22.9 – 70.9 μM) for 48 hr exposure and 9.3 μM (95% CI: 5.7 – 16.5 μM) for 72 hr treatment. Paclitaxel causes dose- and time-dependent changes in neurite network complexity detected by βIII-tubulin staining and high content imaging. The IC50for paclitaxel reduction of neurite area was 1.4μM (95% CI: 0.3 - 16.9μM) for 48 hr exposure and 0.6μM (95% CI: 0.09 - 9.9μM) for 72 hr exposure. Decreased mitochondrial membrane potential, slower movement of mitochondria down the neurites and changes in glutamate-induced neuronal excitability were also observed with paclitaxel exposure. The iPSC-SNs were also sensitive to docetaxel, vincristine and bortezomib. Collectively, these data support the use of iPSC-SNs for detailed mechanistic investigations of genes and pathways implicated in chemotherapy-induced neurotoxicity and the identification of novel therapeutic approaches for its prevention and treatment.
Wistar rats and C57BL/6J mice differ in their motivation to seek social interaction versus food in the Social versus Food Preference Test
Authors: Reppucci C.J. , Brown L.A. , Chambers A.Q. , Veenema A.H. 
Published: June 2020

ABSTRACTHere we characterized the Social versus Food Preference Test, a behavioral paradigm designed to investigate the competition between the choice to seek social interaction versus the choice to seek food. We assessed how this competition was modulated by internal cues (social isolation, food deprivation), external cues (time-of-testing, stimulus salience), sex (males, females), age (adolescents, adults), and rodent model (Wistar rats, C57BL/6J mice). We found that changes in stimulus preference in response to the internal and external cue manipulations were similar across cohorts. Specifically, social over food preference scores were reduced by food deprivation and social familiarly in Wistar rats and C57BL/6J mice of both sexes. Interestingly, the degree of food deprivation-induced changes in stimulus investigation patterns were greater in adolescents compared to adults in Wistar rats and C57BL/6J mice. Strikingly, baseline stimulus preference and investigation times varied greatly between rodent models: across manipulations, Wistar rats were generally more social-preferring and C57BL/6J mice were generally more food-preferring. Adolescent Wistar rats spent more time investigating the social and food stimuli than adult Wistar rats, while adolescent and adult C57BL/6J mice investigated the stimuli a similar amount. Neither social isolation nor time-of-testing altered behavior in the Social versus Food Preference Test. Together, our results indicate that the Social versus Food Preference Test is a flexible behavioral paradigm suitable for future interrogations of the peripheral and central systems that can coordinate the expression of stimulus preference related to multiple motivated behaviors.HIGHLIGHTSRats prefer social over food when sated, and this is attenuated by food deprivation.Mice have no preference when sated, and prefer food over social when food-deprived.Rats prefer a familiar social stimulus or a novel social stimulus over food.Mice prefer food over a familiar social stimulus.Adolescent rats investigate social and food stimuli longer than adult rats.GRAPHICAL ABSTRACT
Variance in cortical depth across the brain surface
Authors: Davis Nick J. 
Published: June 2020

AbstractThe distance between the surface of the scalp and the surface of the grey matter of the brain is a key factor in determining the effective dose of non-invasive brain stimulation for an individual person. The highly folded nature of the cortical surface means that the depth of a particular brain area is likely to vary between individuals. The question addressed here is: what is the variability of this measure of cortical depth? 94 anatomical MRI images were taken from the OASIS database. For each image, the minimum distance from each point in the grey matter to the scalp surface was determined. Transforming these estimates into standard space meant that the coefficient of variation could be determined across the sample. The results indicated that depth variability is high across the cortical surface, even when taking sulcal depth into account. This was true even for the primary visual and motor areas, which are often used in setting TMS dosage. The correlation of the depth of these areas and the depth of other brain areas was low. The results suggest that dose-setting of TMS based on visual or evoked potentials may offer poor reliability, and that individual brain images should be used when targeting non-primary brain areas.
A generative modeling approach for interpreting population-level variability in brain structure
Authors: Liu Ran , Subakan Cem , Balwani Aishwarya H. , Whitesell Jennifer , Harris Julie , Koyejo Sanmi , Dyer Eva 
Published: June 2020

AbstractUnderstanding how neural structure varies across individuals is critical for characterizing the effects of disease, learning, and aging on the brain. However, disentangling the different factors that give rise to individual variability is still an outstanding challenge. In this paper, we introduce a deep generative modeling approach to find different modes of variation across many individuals. To do this, we start by training a variational autoencoder on a collection of auto-fluorescence images from a little over 1,700 mouse brains at 25 micron resolution. To then tap into the learned factors and validate the model’s expressiveness, we developed a novel bi-directional technique to interpret the latent space–by making structured perturbations to both, the high-dimensional inputs of the network, as well as the low-dimensional latent variables in its bottleneck. Our results demonstrate that through coupling generative modeling frameworks with structured perturbations, it is possible to probe the latent space to provide insights into the representations of brain structure formed in deep neural networks.
Trade-offs in Robustness to Perturbations of Bacterial Population Controllers
Authors: McBride Cameron , Del Vecchio Domitilla 
Published: June 2020

AbstractSynthetic biology applications have the potential to have lasting impact; however, there is considerable difficulty in scaling up engineered genetic circuits. One of the current hurdles is resource sharing, where different circuit components become implicitly coupled through the host cell’s pool of resources, which may destroy circuit function. One potential solution around this problem is to distribute genetic circuit components across multiple cell strains and control the cell population size using a population controller. In these situations, perturbations in the availability of cellular resources, such as due to resource sharing, will affect the performance of the population controller. In this work, we model a genetic population controller implemented by a genetic circuit while considering perturbations in the availability of cellular resources. We analyze how these intracellular perturbations and extracellular disturbances to cell growth affect cell population size. We find that it is not possible to tune the population controller’s gain such that the population density is robust to both extracellular disturbances and perturbations to the pool of available resources.
Age-induced methylmalonic acid accumulation promotes tumor progression and aggressiveness
Authors: Gomes Ana P. , Ilter Didem , Low Vivien , Endress Jennifer E. , Fernández-García Juan , Rosenzweig Adam , Schild Tanya , Broekaert Dorien , Ahmed Adnan , Planque Melanie , Elia Ilaria , Han Julie , Kinzig Charles , Mullarky Edouard , Mutvei Anders P. , Asara John , de Cabo Rafael , Cantley Lewis C. , Dephoure Noah , Fendt Sarah-Maria , Blenis John 
Published: June 2020

SummaryFrom age 65 onwards, the risk of cancer incidence and associated mortality is substantially higher1-3. Nonetheless, our understanding of the complex relationship between age and cancer is still in its infancy4. For decades, the link has largely been attributed to increased exposure time to mutagens in older individuals. However, this view does not account for the well-established role of diet, exercise and small molecules that target the pace of metabolic aging5-8. Here, we show that metabolic alterations that occur with age can render a systemic environment favorable to progression and aggressiveness of tumors. Specifically, we show that methylmalonic acid (MMA), a by-product of propionate metabolism, is significantly up-regulated in the serum of older people, and functions as a mediator of tumor progression. We traced this to the induction of SOX4 and a consequent transcriptional reprogramming that can endow cancer cells with aggressive properties. Thus, accumulation of MMA represents a novel link between aging and cancer progression, implicating MMA as a novel therapeutic target for advanced carcinomas.
Heparanase promotes Syndecan-1 expression to mediate fibrillar collagen and mammographic density in human breast tissue culturedex vivo
Authors: Huang Xuan , Reye Gina , Momot Konstantin I. , Blick Tony , Lloyd Thomas , Tilley Wayne D. , Hickey Theresa E. , Snell Cameron E. , Okolicsanyi Rachel K. , Haupt Larisa M. , Ferro Vito , Thompson Erik W. , Hugo Honor J 
Published: June 2020

AbstractMammographic density (MD) is a strong and independent factor for breast cancer (BC) risk and is increasingly associated with BC progression. We have previously shown in mice that high MD, which is characterised by the preponderance of a fibrous stroma, facilitates BC xenograft growth and metastasis. This stroma is rich in extracellular matrix (ECM) factors, including heparan sulfate proteoglycans (HSPGs), such as the BC-associated syndecan-1 (SDC1). These proteoglycans tether growth factors, which are released by heparanase (HPSE). MD is positively associated with estrogen exposure and, in cell models, estrogen has been implicated in the upregulation of HPSE, the activity of which promotes SDC expression. Herein we describe a novel measurement approach (single-sided NMR) using a patient-derived explant (PDE) model of normal human (female) mammary tissue culturedex vivoto investigate the role(s) of HPSE and SDC1 on MD. Relative HSPG gene and protein analyses determined in patient-paired high versus low MD tissues identified SDC1 and SDC4 as potential mediators of MD. Using the PDE model we demonstrate that HPSE promotes SDC1 rather than SDC4 expression and cleavage, leading to increased MD. In this model system, synstatin (SSTN), an SDC1 inhibitory peptide designed to decouple SDC1-ITGαvβ3 parallel collagen alignment, reduced the abundance of fibrillar collagen as assessed by picrosirius red viewed under polarised light, and reduced MD. Our results reveal a potential role for HPSE in maintaining MD via its direct regulation of SDC1, which in turn physically tethers collagen into aligned fibres characteristic of MD. We propose that inhibitors of HPSE and/or SDC1 may afford an opportunity to reduce MD in high BC risk individuals and reduce MD-associated BC progression in conjunction with established BC therapies.
Bioaugmented sand filter columns provide stable removal of pesticide residue from membrane retentate
Authors: Ellegaard-Jensen Lea , Schostag Morten Dencker , Fini Mahdi Nikbakht , Badawi Nora , Gobbi Alex , Aamand Jens , Hansen Lars Hestbjerg 
Published: June 2020

ABSTRACTDrinking water resources, such as groundwater, are threatened by pollution. The pesticide metabolite 2,6-dichlorobenzamide (BAM) is one of the compounds frequently found in groundwater. Studies have attempted to add specific BAM-degrading bacteria to sand-filters at drinking water treatment facilities. This biotechnology has shown great potential in removing BAM from contaminated water. However, the degradation potential was formerly lost after approximately 2-3 weeks due to a decrease of the degrader population over time.The aim of the present study was to overcome the constraints leading to loss of degraders from inoculated filters. Our approach was threefold: 1) Development of a novel inoculation strategy, 2) lowering the flowrate to reduce washout of cells, and 3) increasing the concentration of nutrients hereunder the pollutant in a smaller inlet water stream. The two latter were achieved via modifications of the inlet water by applying membrane treatment which, besides producing an ultra-pure water fraction, produced a residual water stream with nutrients including BAM concentrated in an approximately 10-fold reduced volume. This was done to alleviate starvation of degrader bacteria in the otherwise oligotrophic sand-filters and to enable a decreased flowrate.By this approach, we achieved 100% BAM removal over a period of 40 days in sand-filter columns inoculated with the BAM-degraderAminobactersp. MSH1. Molecular targeting of the degrader strain showed that the population of degrader bacteria persisted at high numbers throughout the sand-filter columns and over the entire timespan of the experiment. 16S rRNA gene amplicon sequencing confirmed that MSH1 dominated the bacterial communities.IMPORTANCEMany countries rely partly or solely on groundwater as the source of drinking water. Here groundwater contamination by pesticide residues poses a serious threat to the production of high quality drinking water. Since scarcity of clean groundwater may occur in progressively larger areas both locally and globally, the need for efficient purification technologies is growing. This study shows that a novel system combining membrane treatment and bioaugmented sand-filters can efficiently remove pesticide residues in laboratory columns when applying specific inoculation and flow conditions. Once upscaled, this system can be used directly for pump-and-treat of contaminated groundwater wells or at drinking water treatment plants.
Characterization of genomic regulation profiles in human mitral valve whole tissue to annotate genetic risk loci for mitral valve prolapse
Authors: Kyryachenko Sergiy , Georges Adrien , Yu Mengyao , Barrandou Takiy , Bruneval Patrick , Rubio Tony , Gronwald Judith , Baraki Hassina , Kutschka Ingo , Norris Russell A , Voigt Niels , Bouatia-Naji Nabila 
Published: June 2020

ABSTRACTRationaleMitral valve prolapse (MVP) is a common valve disease that leads to mitral insufficiency, heart failure and sudden death. The identification of risk loci provided insight into its genetic architecture, although the causal variants and target genes need to be fully characterized.ObjectiveTo establish the chromatin accessibility profiles and gene regulation specificities of human mitral valve and identify functional variants and target genes at MVP loci.Methods and ResultsWe mapped the open chromatin accessible regions in nuclei from 11 human mitral valves by an assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-Seq). Compared to the heart tissue and cardiac fibroblasts, we found that mitral valve-specific ATAC-Seq peaks were enriched near genes involved in extracellular matrix organization, chondrocyte differentiation, and connective tissue development. The most enriched motif in mitral valve-specific open chromatin peaks was for the nuclear factor of activated T cells (NFATC) family of transcription factors, involved in valve endocardial and interstitial cells formation. We also found that MVP-associated variants (p < 10−5) observed in the current MVP GWAS were significantly enriched (p< 0.05) in mitral valve open chromatin peaks. Integration of the ATAC-Seq data with GWAS loci, extensive functional annotation, and gene reporter assay revealed plausible causal variants at two risk loci: rs6723013 at the IGFBP5/TNS1 locus and rs2641440 at the SMG6/SRR locus. Circular chromosome conformation capture followed by high-throughput sequencing provided evidence for several target genes, including SRR, HIC1, and DPH1 at the SMG6/SRR locus and further supported TNS1 as the most likely target gene on Chr2.ConclusionsHere we describe unprecedented genome-wide open chromatin profiles from human mitral valves that indicates specific gene regulation profiles, compared to the heart. We also report in vitro functional evidence for potential causal variants and target genes at MVP risk loci involving established and new biological mechanisms relevant to mitral valve disease.
Improving Risk Assessment of Miscarriage during Pregnancy with Knowledge Graph Embeddings
Authors: Tissot Hegler C. , Pedebos Lucas A. 
Published: June 2020

AbstractMiscarriages are the most common type of pregnancy loss, mostly occurring in the first 12 weeks of pregnancy due to known factors of different natures. Pregnancy risk assessment aims to quantify evidence in order to reduce such maternal morbidities during pregnancy, and personalized decision support systems are the cornerstone of high-quality, patient-centered care in order to improve diagnosis, treatment selection, and risk assessment. However, the increasing number of patient-level observations and data sparsity requires more effective forms of representing clinical knowledge in order to encode known information that enables performing inference and reasoning. Whereas knowledge embedding representation has been widely explored in the open domain data, there are few efforts for its application in the clinical domain. In this study, we discuss differences among multiple embedding strategies, and we demonstrate how these methods can assist on clinical risk assessment of miscarriage both before and specially in the earlier pregnancy stages. Our experiments show that simple knowledge embedding approaches that utilize domain-specific metadata perform better than complex embedding strategies, although both are able to improve results comparatively to a population probabilistic baseline in both AUPRC, F1-score, a proposed normalized version of these evaluation metrics that better reflects accuracy for unbalanced datasets.