bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal Automatic Segmentation of Hippocampal Subfields (LASHiS) using Multi-Contrast MRI
Authors: Shaw Thomas , York Ashley , Ziaei Maryam , Barth Markus , Bollmann Steffen ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: September 2019

AbstractThe volumetric and morphometric examination of hippocampus formation subfields in a longitudinal manner using in vivo MRI could lead to more sensitive biomarkers for neuropsychiatric disorders and diseases including Alzheimer’s disease, as the anatomical subregions are functionally specialised. Longitudinal processing allows for increased sensitivity due to reduced confounds of inter-subject variability and higher effect-sensitivity than cross-sectional designs. We examined the performance of a new longitudinal pipeline (Longitudinal Automatic Segmentation of Hippocampus Subfields [LASHiS]) against three freely available, published approaches. LASHiS automatically segments hippocampus formation subfields by propagating labels from cross-sectionally labelled time point scans using joint-label fusion to a non-linearly realigned ‘single subject template’, where image segmentation occurs free of bias to any individual time point. Our pipeline measures tissue characteristics available in in vivo high-resolution MRI scans, at both clinical (3 Tesla) and ultra-high field strength (7 Tesla) and differs from previous longitudinal segmentation pipelines in that it leverages multi-contrast information in the segmentation process. LASHiS produces robust and reliable automatic multi-contrast segmentations of hippocampus formation subfields, as measured by higher volume similarity coefficients and Dice coefficients for test-retest reliability and robust longitudinal Bayesian Linear Mixed Effects results at 7 T, while showing sound results at 3 T. All code for this project including the automatic pipeline is available at https://github.com/CAIsr/LASHiS
Studying functional brain networks from dry electrode EEG set during music and resting states in neurodevelopment disorder
Authors: Sareen Ekansh , Gupta Anubha , Verma Rohit , Achary G. Krishnaveni , Varkey Blessin 
Published: September 2019

AbstractThere has been an emerging interest in the study of functional brain networks in cognitive neuroscience in order to better understand brain responses to different stimuli. Such studies can help in understanding brain connectivity alterations that arise in neurodevelopmental disorders such as intellectual disability (ID). This research contributes to this body of knowledge by studying alterations in brain connectivity in ID compared to the typically developing controls (TDC). Electroencephalography (EEG) data of subjects with ID and TDC is collected through limited channel dry electrode system. Data was analyzed for the auditory and rest state processing along with the study of intra-network connectivity of the brain via clustering coefficients. Research findings indicate evidences for links between the sensory deficits and social impairment in ID individuals.
Reward Evokes Visual Perceptual Learning Following Reinforcement Learning Rules
Authors: Wang Zhiyan , Kim Dongho , Pedroncelli Giorgia , Sasaki Yuka , Watanabe Takeo 
Published: September 2019

AbstractVisual perceptual learning (VPL) is defined as a long-term performance enhancement as a result of visual experiences. A number of studies have demonstrated that reward can evoke VPL. However, the mechanisms of how reward evoke VPL remain unknown. One possible hypothesis is that VPL is obtained through reward related reinforcement processing. If this hypothesis is true, learning can only occur when reward follows the stimulus presentation. Another interpretation is that VPL is acquired through an enhancement of alertness in association with reward. If the alertness hypothesis is true, learning should occur when reward precedes the stimulus presentation. In our study, we tested the plausibility of the two hypotheses by manipulating the order of reward and stimulus presentation. In Experiment 1, we separated participants into two groups. During training, the ‘Before’ group received water reward 400ms prior to the onset of trained orientation stimulus while the ‘After’ group received water reward 400ms subsequent to the onset of trained orientation stimulus. Both groups were trained using the Continuous Flash Suppression paradigm to render the stimulus imperceptible to the participants by the presentation of dynamic noise in the untrained eye. We found training only in the ‘After’ group indicating that reward may evoke learning through reinforcement-like processing. In Experiment 2, we excluded the possibility that alertness may not be sufficient to elicit learning when presented before stimulus. We presented beep sound prior to the onset of stimulus to increase alertness. Our finding demonstrated that alertness is sufficient enough to evoke learning. In conclusion, our study provided evidence that reward can evoke VPL through reinforcement process.
Visualizing cellular heterogeneity by quantifying the dynamics of MAPK activity in live mammalian cells with synthetic fluorescent biosensors
Authors: Ma Min , Bordignon Pino , Dotto Gian-Paolo , Pelet Serge 
Published: September 2019

AbstractMitogen-Activated Protein Kinases (MAPKs) control a wide array of cellular functions by transducing extracellular information into defined biological responses. In order to understand how these pathways are regulated, dynamic single cell measurements are highly needed. Fluorescence microscopy is well suited to perform these measurements, however, more dynamic and sensitive biosensors that allow the quantification of signaling activity in living mammalian cells are required. We have engineered a synthetic fluorescent substrate for human MAPKs that relocates from the nucleus to the cytoplasm when phosphorylated by the kinase. We demonstrate that this reporter provides a better sensitivity relative to other similar biosensors and has allowed the monitoring of ERK MAPK activity pulses upon a single physiological EGF stimulation. In addition, we display its applicability to other MAPKs and in multiple cancer cell lines or primary cells as well as its application in vivo in developing tumors. Using our newly developed biosensors, dynamic single cell measurements with high temporal resolution can be obtained. These reporters can be widely applied to the analysis of molecular mechanisms of MAPK signaling in healthy and diseased state, in cell culture assays or in vivo.
Deep learning models predict regulatory variants in pancreatic islets and refine type 2 diabetes association signals
Authors: Wesolowska-Andersen Agata , Yu Grace Zhuo , Nylander Vibe , Abaitua Fernando , Thurner Matthias , Torres Jason , Mahajan Anubha , Gloyn Anna L , McCarthy Mark I 
Published: September 2019

AbstractGenome-wide association analyses have uncovered multiple genomic regions associated with T2D, but identification of the causal variants at these remains a challenge. There is growing interest in the potential of deep learning models - which predict epigenome features from DNA sequence - to support inference concerning the regulatory effects of disease-associated variants. Here, we evaluate the advantages of training convolutional neural network (CNN) models on a broad set of epigenomic features collected in a single disease-relevant tissue – pancreatic islets in the case of type 2 diabetes (T2D) - as opposed to models trained on multiple human tissues. We report convergence of CNN-based metrics of regulatory function with conventional approaches to variant prioritization – genetic fine-mapping and regulatory annotation enrichment. We demonstrate that CNN-based analyses can refine association signals at T2D-associated loci and provide experimental validation for one such signal. We anticipate that these approaches will become routine in downstream analyses of GWAS.
CD99 regulates cancer cell transendothelial migration and endothelial cell function via CDC42 and actin remodelling
Authors: Mannion Aarren J. , Odell Adam F. , Taylor Alison , Jones Pamela F. , Cook Graham P 
Published: September 2019

AbstractMetastasis requires tumour cells to cross endothelial cell (EC) barriers and this occurs using mechanisms similar to those used by extravasating leucocytes during inflammation. The cell surface receptor CD99 is expressed by leucocytes and EC and participates in inflammatory transendothelial migration (TEM). CD99 is also expressed by tumour cells and we have analysed its role in tumour progression and cancer cell TEM. In a xenograft model, CD99 expression inhibited the metastatic progression of human breast cancer.In vitro, tumour cell CD99 was required for adhesion to ECs. However, tumour cell CD99 inhibited the invasion of the endothelial barrier by breast and prostate cancer cells and TEM itself. Furthermore, tumour cell CD99 depletion was associated with cytoskeletal remodelling. Loss of EC CD99 enhanced endothelial barrier function and reduced tumour cell TEM. Mechanistically, CD99 loss enhanced the expression and activity of CDC42, a known cytoskeletal organiser. CDC42 positively regulates EC angiogenic activity and the enhanced CDC42 activity resulting from loss of EC CD99 increased angiogenesis. As a signal transduction hub, CDC42 activity impacts upon many of the hallmarks of cancer. The functional link between CD99 and CDC42 identified here implicates CD99 in regulating these diverse pathways by modulation of CDC42 activity.
Experience-dependent reorganization drives development of a binocularly unified cortical representation of orientation
Authors: Whitney David , Chang Jeremy T. , Fitzpatrick David 
Published: September 2019

SummaryAcross sensory areas, neural microcircuits consolidate diverse streams of information into unified, representations of the external world. In the carnivore visual cortex, where eye-specific inputs converge, it has been posited that a single, shared columnar representation of orientation develops independent of sensory experience. In this study, in vivo calcium imaging with columnar and cellular resolution reveals a strikingly different developmental process in ferret visual cortex, starting with an early developmental period in which contralateral, ipsilateral or binocular stimulation each yield distinct well-organized representations of orientation that are misaligned at the columnar and cellular scale. Experience-dependent processes drive the reorganization of these three representations towards a single binocularly-aligned representation resembling the early binocular representation through concerted shifts in the preferred orientation of individual neurons. Thus, contrary to previous findings, a unified binocular representation of orientation results from an experience-dependent process that aligns the activity patterns of three distinct neural representations.
A simple method to determine the elimination half-life of drugs displaying noncumulative toxicity
Authors: Nagarajan Deepesh , Venkatesh Preetham , Thakur Chandrani , Datey Akshay , Chandra Nagasuma , Chakravortty Dipshikha 
Published: September 2019

ABSTRACTThe pharmacokinetic characterization of a drug, especially the determination of its biological half-life, is an essential step during the early phases of drug development. An adequate half-life is amongst the many properties needed for selecting a drug candidate for clinical trials. Conversely, drug candidates possessing inadequate half-lives may be modified or eliminated from the drug discovery pipeline altogether. Several methods exist for determining the half-lives of drugs, namely HPLC, fluorescence assays, radioassays, radioimmunoassays, and elemental mass spectrometric assays. However, all these techniques are resource and labor-intensive, and cannot be used for the high-throughput half-life determination of hundreds of drug candidates. Here, we describe TOXHL: a simple technique to determine the half-lives of compounds displaying noncumulative toxicity. To calculate the half life, TOXHLonly relies on the survival outcomes of three experiments performed on an animal model: an acute toxicity experiment, a cumulative toxicity experiment, and a multi-dose experiment at different dosing intervals. As a proof of concept, we use TOXHLto determine the peritoneal half-life of Ω76, an antimicrobial peptide. The half-life of Ω76 determined by TOXHLis in good agreement with results from a standard mass spectrometric method, validating this approach.
Expressed barcodes enable clonal characterization of chemotherapeutic responses in chronic lymphocytic leukemia
Authors: Al’Khafaji Aziz , Gutierrez Catherine , Brenner Eric , Durrett Russell , Johnson Kaitlyn E. , Zhang Wandi , Li Shuqiang , Livak Kenneth J. , Neuberg Donna , Brock Amy , Wu Catherine J. 
Published: September 2019

AbstractThe remarkable evolutionary capacity of cancer is a major challenge to current therapeutic efforts. Fueling this evolution is its vast clonal heterogeneity and ability to adapt to diverse selective pressures. Although the genetic and transcriptional mechanisms underlying these responses have been independently evaluated, the ability to couple genetic alterations present within individual clones to their respective transcriptional or functional outputs has been lacking in the field. To this end, we developed a high-complexity expressed barcode library that integrates DNA barcoding with single-cell RNA sequencing through use of the CROP-seq sgRNA expression/capture system, and which is compatible with the COLBERT clonal isolation workflow for subsequent genomic and epigenomic characterization of specific clones of interest. We applied this approach to study chronic lymphocytic leukemia (CLL), a mature B cell malignancy notable for its genetic and transcriptomic heterogeneity and variable disease course. Here, we demonstrate the clonal composition and gene expression states of HG3, a CLL cell line harboring the common alteration del(13q), in response to front-line cytotoxic therapy of fludarabine and mafosfamide (an analog of the clinically used cyclophosphamide). Analysis of clonal abundance and clonally-resolved single-cell RNA sequencing revealed that only a small fraction of clones consistently survived therapy. These rare highly drug tolerant clones comprise 94% of the post-treatment population and share a stable, pre-existing gene expression state characterized by upregulation of CXCR4 and WNT signaling and a number of DNA damage and cell survival genes. Taken together, these data demonstrate at unprecedented resolution the diverse clonal characteristics and therapeutic responses of a heterogeneous cancer cell population. Further, this approach provides a template for the high-resolution study of thousands of clones and the respective gene expression states underlying their response to therapy.
Delineating the rules for structural adaptation of membrane-associated proteins to evolutionary changes in membrane lipidome
Authors: Makarova Maria , Peter Maria , Balogh Gabor , Glatz Attila , MacRae James I. , Mora Nestor Lopez , Booth Paula , Makeyev Eugene , Vigh Laszlo , Oliferenko Snezhana 
Published: September 2019

SummaryMembrane function is fundamental to life. Each species explores membrane lipid diversity within a genetically predefined range of possibilities. How membrane lipid composition in turn defines the functional space available for evolution of membrane-centered processes remains largely unknown. We address this fundamental question using related fission yeastsSchizosaccharomyces pombeandSchizosaccharomyces japonicus. We show that unlikeS. pombethat generates membranes where both glycerophospholipid acyl tails are predominantly 16-18 carbons long,S. japonicussynthesizes unusual ‘asymmetrical’ glycerophospholipids where the tails differ in length by 6-8 carbons. This results in stiffer bilayers with distinct lipid packing properties. RetroengineeredS. pombesynthesizing theS. japonicus-type phospholipids exhibits unfolded protein response and downregulates secretion. Importantly, our protein sequence comparisons and domain swap experiments indicate that transmembrane helices co-evolve with membranes, suggesting that, on the evolutionary scale, changes in membrane lipid composition may necessitate extensive adaptation of the membrane-associated proteome.
Evidence for incipient alarm signalling in fish
Authors: Wisenden Brian D. 
Published: September 2019

AbstractIn Focus: Bairos‐Novak, K.R., Ferrari, M.C.O., & Chivers, D.P. (2019). A novel alarm signal in aquatic prey: Familiar minnows coordinate group defences against predators through chemical disturbance cues. Journal of Animal Ecology, 88, 1281–1290, https://doi.org/10.1111/1365-2656.12986. Chemicals released during predation have long been studied as cues to nearby prey that predators are active in the vicinity. Until now, these chemicals have been labelled as cues because there was no compelling evidence for the necessary components of a communication system, namely (a) voluntary control of release of information, (b) capacity for graded responses and (c) the presence of specialized structures for the production and release of the signal. New findings by Bairos‐Novak, Ferrari, and Chivers (2019) show that fathead minnows alter the potency of disturbance “cues” when in the presence of other fathead minnows compared to when they are alone and produce either more or different disturbance “cues” when in the presence of familiar conspecifics compared to when they are in the presence of unfamiliar conspecifics. The behavioural response to these cues is shoaling, which would confer fitness benefits to the sender, thereby qualifying as a signal rather than a cue. This is a significant advancement in the field of chemical ecology of aquatic organisms because disturbance “cues” by fathead minnows bear two of the three hallmarks of an incipient disturbance “signal”.
A Meta‐Analysis of School Quality Capitalization in U.S. House Prices
Authors: Turnbull Geoffrey K. , Zheng Minrong 
Published: September 2019

AbstractSchool quality capitalization studies report widely mixed results. This article conducts meta‐analysis to identify the data characteristics and research methods that explain this variation. The way the school quality is measured matters but no single measure clearly dominates. Both boundary and neighborhood fixed effects significantly control for the influence of neighborhood amenities. Increasing the number of quality variables reduces the capitalization significance of each. Regional differences also appear to matter; studies using data drawn from the South exhibit weaker capitalization. Also, it is surprising that econometric methods do not appear to be driving results.
Sample Mining and Data Mining: Combined Real‐Time and Retrospective Approaches for the Identification of Emerging Novel Psychoactive Substances
Authors: Krotulski Alex J. , Varnum Susan Jansen , Logan Barry K. 
Published: September 2019

AbstractNovel psychoactive substances (NPS) are synthetic drugs that pose serious public health and safety concerns. A multitude of NPS have been identified in the United States, often implicated in forensic investigations. The most common and effective manner for identifying NPS is by use of mass spectrometry and the true utility lies within nontargeted acquisition techniques. During this study, a liquid chromatography quadrupole time‐of‐flight mass spectrometry (LC‐QTOF‐MS) assay was developed, validated, and implemented for forensic toxicology testing. A SCIEX TripleTOF™ 5600 + with SWATH® acquisition was used. Resulting data were compared against an extensive library database containing more than 800 compounds. The LC‐QTOF‐MS assay was applied to the reanalysis of biological sample extracts to discover emergent NPS. More than 3,000 sample extracts were analyzed, and more than 20 emerging NPS were detected for the first time. Among these were isopropyl‐U‐47700, 3,4‐methylenedioxy‐U‐47700, fluorofuranylfentanyl, N‐methyl norfentanyl, 2F‐deschloroketamine, 3,4‐methylenedioxy‐alpha‐PHP, eutylone, and N‐ethyl hexedrone.
Impact of nutritional status, muscle mass and oral status on recovery of full oral intake among stroke patients receiving enteral nutrition: A retrospective cohort study
Authors: Nishioka Shinta , Yamasaki Kazumi , Ogawa Kenji , Oishi Kana , Yano Yoko , Okazaki Yuka , Nakashima Ryusei , Kurihara Masaki 
Published: September 2019

AbstractAimTo clarify the correlation between malnutrition, muscle mass and oral status, and swallowing function recovery in stroke patients receiving enteral nutrition.MethodsPatients with stroke and dysphagia receiving any amount of enteral nutrition in rehabilitation wards from 2012 to 2016 were eligible for inclusion in this retrospective study. On admission, body composition by bioimpedance analysis, malnutrition confirmed by the European Society for Clinical Nutrition and Metabolism criteria, oral status, functional independence measure and demographic data were collected. Characteristics were compared between “oral intake alone” and “artificial nutrition” groups based on the discharge status. Kaplan‐Meier methods and the Cox proportional hazards model were used to determine explanatory factors for the probability of full oral intake.ResultsAmong 174 patients, 113 were analysed (55 women; median age, 77 years). Overall, 61% and 39% were classified as “oral intake alone” and “artificial nutrition,” respectively. Days from onset to admission to rehabilitation wards and motor Functional Independence Measure were higher in the “oral intake alone” group. Kaplan‐Meier analysis demonstrated that patients with lower muscle mass exhibited lower probability of full oral intake (P = .009). The Cox proportional hazards model suggested that lower muscle mass (hazard ratio, 0.493; 95% CI, 0.286‐0.850) and poor oral hygiene (hazard ratio, 0.573; 95% CI, 0.333‐0.987) were independently correlated with “oral intake alone” status. Malnutrition and other oral status are not related to achieving full oral intake.ConclusionsSkeletal muscle mass and oral hygiene are independently correlated with full oral intake among stroke patients receiving enteral nutrition during the rehabilitation phase.
HLA‐DQ genotypes relative risks for celiac disease in Arabs: A case‐control study
Authors: Al‐Hussaini Abdulrahman , Eltayeb‐Elsheikh Nezar , Alharthi Hanan , Osman Awad , Alshahrani Maram , Sandogji Ibrahim , Alrashidi Sami , Bashir Muhammed Salman 
Published: September 2019

ObjectivesIt remains unknown what degree of risk is conferred by celiac disease (CD)‐predisposing human leukocyte antigen (HLA)‐DQ genotypes in Saudi Arabia compared with in Western countries. In this study, we aimed to determine the CD risk gradient associated with the HLA‐DQ genotypes and to compare HLA‐DQ genotypes between symptomatic patients with CD and screening‐identified asymptomatic CD patients.MethodsWe enrolled three groups of subjects, including 46 CD children diagnosed consecutively over the past 10 years, 54 CD children diagnosed during a mass screening of schoolchildren, and 192 healthy controls. All the participants were typed for the HLA‐DQA1 and HLA‐DQB1 genes by polymerase chain reaction sequence‐specific oligonucleotide probes.ResultsComparing the patients with CD to controls, we identified 5 groups in the CD risk gradient: (i) very high risk associated with the DQ2.5/DQ8 genotype (odds ratio [OR] 46.93); (ii) high risk (homozygous DQ2.5, DQ2.5/DQ2.2; OR 4.12‐5.04); (iii) intermediate risk (heterozygous DQ2.5, DQ8/DQ2.2; OR 1.61 and 1.67); (iv) low risk (DQ8, DQ2.2); and (v) very low risk (DQ2.x, DQX.5, DQX.x). Heterozygous DQ8 was more common in screening‐identified group compared to symptomatic patients (13.0% vs 2.2%); however, other genotypes were very similar between the two groups.ConclusionThe highest risk of developing CD in our Saudi Arabia population is associated with the DQ2.5/DQ8 genotype.