bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automated interpretation of the coronary angioscopy with deep convolutional neural networks
Authors: Miyoshi Toru , Higaki Akinori , Kawakami Hideo , Yamaguchi Osamu 
Published: July 2019

AbstractBackgroundCoronary angioscopy (CAS) is a useful modality to assess atherosclerotic changes, but interpretation of the images requires expert knowledge. Deep convolutional neural networks (DCNN) can be used for diagnostic prediction and image synthesis.Methods107 images from 47 patients, who underwent coronary angioscopy in our hospital between 2014 and 2017, and 864 images, selected from 142 MEDLINE-indexed articles published between 2000 and 2019, were analyzed. First, we developed a prediction model for the angioscopic findings. Next, we made a generative adversarial networks (GAN) model to simulate the CAS images. Finally, we tried to control the output images according to the angioscopic findings with conditional GAN architecture.ResultsFor both yellow color (YC) grade and neointimal coverage (NC) grade, we could observe strong correlations between the true grades and the predicted values (YC grade, average r value = 0.80 ± 0.02, p-value <0.001; NC grade, average r value = 0.73 ± 0.02, p < 0.001). The binary classification model for the red thrombus yielded 0.71 ± 0.03 F1-score and the area under the ROC curve (AUC) was 0.91 ± 0.02. The standard GAN model could generate realistic CAS images (average Inception score = 3.57 ± 0.06). GAN-based data augmentation improved the performance of the prediction models. In the conditional GAN model, there were significant correlations between given values and the expert’s diagnosis in YC grade and NC grade.ConclusionDCNN is useful in both predictive and generative modeling that can help develop the diagnostic support system for CAS.
The relationship between antihypertensive medications and mood disorders: analysis of linked healthcare data for 1.8 million patients
Authors: Shaw Richard J , Mackay Daniel , Pell Jill P. , Padmanabhan Sandosh , Bailey David S. , Smith Daniel J. 
Published: July 2019

AbstractBackgroundRecent work suggests that antihypertensive medications may be useful as repurposed treatments for mood disorders. Using large-scale linked healthcare data we investigated whether certain classes of antihypertensive, such as angiotensin antagonists and calcium channel blockers, were associated with reduced risk of new-onset Major Depressive Disorder (MDD) or bipolar disorder.MethodTwo cohorts of patients treated with antihypertensives were identified from Scottish prescribing (2009-2016) and hospital admission (1981-2016) records. Eligibility for cohort membership was determined by receipt of a minimum of four prescriptions for antihypertensives within a 12-month window. One treatment cohort (n=538,730) included patients with no previous history of mood disorder, whereas the other (n=262,278) included those who did. Both cohorts were matched by age, sex and area deprivation to untreated comparators. Associations between antihypertensive treatment and new-onset MDD or bipolar episodes were investigated using Cox regression.ResultsFor patients without a history of mood disorder, antihypertensives were associated with increased risk of new-onset MDD. For angiotensin antagonist monotherapy, the hazard ratio (HR) for new-onset MDD was 1.17 (95%CI 1.04-1.31). Beta blockers’ association was stronger (HR 2.68; 95%CI 2.45-2.92), possibly indicating pre-existing anxiety. Some classes of antihypertensive were associated with protection against bipolar disorder, particularly angiotensin antagonists (HR 0.46; 95%CI 0.30-0.70). For patients with a past history of mood disorders, all classes of antihypertensives were associated with increased risk of future episodes of MDD.ConclusionsThere was no evidence that antihypertensive medications prevented new episodes of MDD but angiotensin antagonists may represent a novel treatment avenue for bipolar disorder.
First detection of Infectious Spleen and kidney Necrosis Virus (ISKNV) associated with massive mortalities in farmed tilapia in Africa
Authors: Ramírez-Paredez José Gustavo , Paley Richard K. , Hunt William , Feist Stephen W. , Stone David M. , Field Terence R. , Haydon David J. , Ziddah Peter A. , Nkansa Mary , Pecku Emanuel K. , Awuni Joseph A. , Guilder James , Gray Joshua , Duodu Samuel , Wallis Timothy S. , Verner-Jeffreys David W. 
Published: July 2019

SummaryIn late 2018, unusual patterns of very high mortality (>50% production) were reported in intensive tilapia cage culture systems across Lake Volta in Ghana. Samples of fish and fry were collected and analysed from two affected farms between October 2018 and February 2019. Affected fish showed darkening, erratic swimming and abdominal distension with associated ascites. Histopathological observations of tissues taken from moribund fish at different farms revealed lesions indicative of viral infection. These included haematopoietic cell nuclear and cytoplasmic pleomorphism with marginalisation of chromatin and fine granulation. Transmission electron microscopy showed cells contained conspicuous virions with typical Iridovirus morphology i.e. enveloped, with icosahedral and or polyhedral geometries and with a diameter c.160 nm. PCR confirmation and DNA sequencing identified the virions as Infectious Spleen and Kidney Necrosis Virus (ISKNV). Samples of fry and older animals were all strongly positive for the presence of the virus by qPCR. All samples tested negative for TiLV and Nodavirus by qPCR. All samples collected from farms prior to the mortality event were negative for ISKNV. Follow up testing of fish and fry sampled from 5 additional sites in July 2019 showed all farms had fish that were PCR positive for ISKNV, whether there was active disease on the farm or not, demonstrating the disease was endemic to farms all over Lake Volta by that point. The results suggest that ISKNV was the cause of disease on the investigated farms and likely had a primary role in the mortality events. A common observation of coinfections with Streptococcus agalactiae and other tilapia bacterial pathogens further suggests that these may interact to cause severe pathology, particularly in larger fish. Results demonstrate that there are a range of potential threats to the sustainability of tilapia aquaculture that need to be guarded against.
Independent origin of MIRNA genes controlling homologous target genes by partial inverted duplication of antisense-transcribed sequences
Authors: Gramzow Lydia , Lobbes Dajana , Walter Sophia , Innard Nathan , Theißen Günter 
Published: July 2019

AbstractSome microRNAs (miRNAs) are key regulators of developmental processes, mainly by controlling the accumulation of transcripts encoding transcription factors that are important for morphogenesis. MADS-box genes encode a family of transcription factors which control diverse developmental processes in flowering plants. Here we study the convergent evolution of two MIRNA (MIR) gene families, named MIR444 and MIR824, targeting members of the same clade of MIKCC-group MADS-box genes. We show that these two MIR genes most likely originated independently in monocots (MIR444) and in Brassicales (eudicots, MIR824). We provide evidence that in both cases the future target gene was transcribed in antisense prior to the evolution of the MIR genes. Both MIR genes then likely originated by a partial inverted duplication of their target genes, resulting in natural antisense organization of the newly evolved MIR gene and its target gene at birth. We thus propose a new model for the origin of MIR genes, MEPIDAS (MicroRNA Evolution by Partial Inverted Duplication of Antisense-transcribed Sequences). MEPIDAS is a refinement of the inverted duplication hypothesis. According to MEPIDAS, a MIR gene evolves at a genomic locus at which the future target gene is also transcribed in the antisense direction. A partial inverted duplication at this locus causes the antisense transcript to fold into a stem-loop structure that is recognized by the miRNA biogenesis machinery to produce a miRNA that regulates the gene at this locus. Our analyses exemplify how to elucidate the origin of conserved miRNAs by comparative genomics and will guide future studies.
Spatial variation in black-headed night monkey (Aotus nigriceps) vocalizations
Authors: Helenbrook W. D. , Linck N. A. , Pardo M. A. , Suarez J. A. 
Published: July 2019

AbstractQuantitative acoustic analysis has been used to decipher individual differences, population structure, and taxonomic diversity in numerous primate species. We previously described three distinct call types in wildAotus nigriceps, and now assess acoustic differences in two of these call types between social groups and spatially distinct populations. Acoustic parameters for both analyzed call types exhibited significant variability between groups. Similarly, geographically distant field sites were acoustically distinct from one another. Several groups also used a variation of a common call: a triplet Ch Ch instead of a duplicate. Other groups made use of ultrasonic frequencies which have not previously been reported inAotus. Our results suggest thatAotus nigricepsexhibits substantial acoustic variability across sites that could potentially be useful for taxonomic classification, although additional geographically distant populations still need to be sampled. The possibility of individual signatures also exists and will require recording vocalizations from known individuals.
Female rats consume and prefer oxycodone more than males in a chronic two-bottle oral voluntary choice paradigm
Authors: Zanni Giulia , DeSalle Matthew J. , Deutsch Hannah M. , Barr Gordon A. , Eisch Amelia J. 
Published: July 2019

ABSTRACTThe increased abuse of opioids - such as oxycodone - poses major challenges for health and socioeconomic systems. Human prescription opioid abuse is marked by continuous, voluntary, oral intake, and sex differences. Therefore the field would benefit from a preclinical in-depth characterization of sex differences in a chronic oral voluntary, free choice, and continuous access paradigm. Here we show in an oral oxycodone continuous access two-bottle choice paradigm sex-dependent voluntary drug intake, dependence, and motivation to take the drug. Adult female and male Long-Evans rats were given unlimited, continuous home cage access to two bottles containing water (Control) or one bottle of water and one bottle of oxycodone dissolved in water (Experimental). Most experimental rats voluntarily drank oxycodone (∼10 mg/kg/day) and escalated their intake over 22 weeks. Females self-administered twice as much oxycodone as males, leading to greater blood levels of oxycodone, and engaged in more gnawing behavior. Precipitated withdrawal revealed high levels of dependence in both sexes. Reflecting motivation to drink oxycodone, ascending concentration of citric acid suppressed the intake of oxycodone (Experimental) and the intake of water (Control); however Experimental rats returned to pre-citric acid preference levels whereas Controls rats did not. Thus, female rats consumed and preferred oxycodone more than males in this chronic two-bottle oral choice paradigm. Both sexes displayed many features of human oxycodone abuse, and behavioral pre-screening predicted parameters of intake and withdrawal. This model provides an additional paradigm for understanding mechanisms that mediate long-term voluntary drug use and for exploring potential treatment options.HIGHLIGHTSAdult rats offered continuous choice of oral oxycodone vs. water preferred oxycodoneRats self-titrated oxycodone, yet females preferred and escalated more than malesBoth sexes were motivated to drink oxycodone, as shown by a citric acid aversion testBoth sexes became dependent on oxycodone, as shown by precipitated withdrawalBehavioral prescreening predicted later aspects of oxycodone intake and dependence
Sensitivity and specificity of a Bayesian single trial analysis for time varying neural signals
Authors: Mohl Jeff T. , Caruso Valeria C. , Tokdar Surya T. , Groh J. M. 
Published: July 2019

AbstractWe recently reported the existence of fluctuations in neural signals that may permit neurons to code multiple simultaneous stimuli sequentially across time1. This required deploying a novel statistical approach to permit investigation of neural activity at the scale of individual trials. Here we present tests using synthetic data to assess the sensitivity and specificity of this analysis. We fabricated datasets to match each of several potential response patterns derived from single-stimulus response distributions. In particular, we simulated dual stimulus trial spike counts that reflected fluctuating mixtures of the single stimulus spike counts, stable intermediate averages, single stimulus winner-take-all, or response distributions that were outside the range defined by the single stimulus responses (such as summation or suppression). We then assessed how well the analysis recovered the correct response pattern as a function of the number of simulated trials and the difference between the simulated responses to each “stimulus” alone. We found excellent recovery of the mixture, intermediate, and outside categories (>97% correct), and good recovery of the single/winner-take-all category (>90% correct) when the number of trials was >20 and the single-stimulus response rates were 50Hz and 20Hz respectively. Both larger numbers of trials and greater separation between the single stimulus firing rates improved categorization accuracy. These results provide a benchmark, and guidelines for data collection, for use of this method to investigate coding of multiple items at the individual-trial time scale.
A Systems Immunology Approach Identifies Cytokine-Induced STAT Signaling Pathways Critical to Rheumatoid Arthritis Disease Activity and Treatment Response
Authors: Ptacek Jason , Hawtin Rachael E. , Sun Dongmei , Louie Brent , Evensen Erik , Mittleman Barbara , Cesano Alessandra , Cavet Guy , Bingham Clifton O. , Cofield Stacey S. , Curtis Jeffrey R. , Danila Maria I. , Raman Chander , Furie Richard , Genovese Mark C. , Robinson William H. , Levesque Marc C. , Moreland Larry W. , Nigrovic Peter A. , Shadick Nancy A. , O’Dell James R. , Thiele Geoffrey M. , Clair E. William St , Striebich Christopher C. , Hale Matthew B. , Khalili Houman , Batliwalla Franak , Aranow Cynthia , Mackay Meggan , Diamond Betty , Nolan Garry P. , Gregersen Peter K. , Bridges S. Louis 
Published: July 2019

AbstractRheumatoid arthritis (RA), a chronic autoimmune disease characterized by circulating autoantibodies, involves many cytokine-mediated signaling pathways in multiple immune cell subsets. Most studies of immune cells in RA have limitations, such as analysis of a small number of cell subsets or pathways, and limited longitudinal data on patient phenotypes. In this study, we used an innovative systems immunology approach to simultaneously quantify up to 882 signaling nodes (Jak/STAT signaling readouts modulated by cytokines and other stimuli) in 21 immune cell subsets. We studied 194 RA patients and 41 controls, including 146 well-characterized RA patients prior to, and 6 months after, initiation of methotrexate or biologic agents from the Treatment Efficacy and Toxicity in RA Database and Repository (TETRAD). There was strikingly attenuated signaling capacity in RA patients in IFNα stimulation followed by measurement of phosphorylated STAT1 [IFNα→p-STAT1] in six immune cell subsets. Multiple nodes showed negative association with disease activity, including IFNα→STAT5 signaling in naive and memory B cells. In contrast, IL-6-induced STAT1 and STAT3 activation in central memory CD4-negative T cells showed a positive association with disease activity. Multiple nodes were associated with treatment response, including IFNα→STAT1 in monocytes and IL-6→STAT3 in CD4+ naive T cells. Decision tree analysis identified a model combining these two nodes as a high-performing classifier of treatment response to TNF inhibitors. Our study provides novel information on RA disease mechanisms and serves as a framework for the discovery and validation of biomarkers of treatment response in RA.
Drug screening to identify compounds to act as co-therapies for the treatment of pathogenic Burkholderia
Authors: Barker Sam , Harding Sarah V. , Gray David , Richards Mark I. , Atkins Helen S. , Harmer Nicholas 
Published: July 2019

AbstractBurkholderia pseudomallei is a soil-dwelling organism present throughout the tropics, and is the causative agent of melioidosis, a disease that is believed to kill 89,000 people per year. It is naturally resistant to most currently available antibiotics. The most efficacious treatment for melioidosis requires at least two weeks of intravenous treatment with ceftazidime or meropenem. This places a large treatment burden on the predominantly middle income nations where the majority of disease occurs. We have established a high-throughput assay for compounds that could be used as a co-therapy to potentiate the effect of ceftazidime, using the related non-pathogenic bacterium Burkholderia thailandensis as a surrogate. Optimization of the assay gave a Z’ factor of 0.68. We screened a library of 61,250 compounds, and identified 29 compounds with a pIC50 (-log10(IC50)) greater than five. Detailed investigation allowed us to down select to six “best in class” compounds, which included the licensed drug chloroxine. Co-treatment of B. thailandensis with ceftazidime and chloroxine reduced culturable cell numbers by two orders of magnitude over 48 hours compared to treatment with ceftazidime alone. Hit expansion around chloroxine was performed using commercially available compounds. Minor modifications to the structure abolished activity, suggesting that chloroxine likely acts against a specific target. Finally, preliminary data also demonstrates the utility of chloroxine to act as a co-therapy to potentiate the effect of ceftazidime against B. pseudomallei. This approach successfully identified potential co-therapies for a recalcitrant Gram-negative bacterial species. Our assay could be used more widely to aid in chemotherapy against these bacteria.
Understanding behavior in a captive Lion-tailed macaques (Macaca silenus) group
Authors: Mazumder Jayashree 
Published: July 2019

AbstractA captive lion-tailed macaque group, consisting of two adult males and one adult female, was observed over a period of three months. We collected the data from 8.30hrs to 17.30hrs, using both focal and scan animal sampling methods. In the study, we divided the behaviors into abnormal and normal behavioral traits which were further divided into self-directed and social interchange behaviors. When compared with the past records on the wild and captive group, most of the behaviors were similar which included behaviors like forage, grooming, aggressive display and reproductive behavior. Animals who were born in a zoo or confiscated from another zoo showed higher levels of abnormal behaviors. The results of this study discuss the range of behavioral patterns displayed by the captive animals, discuss the causal factors for the behavioral pathogens, and further suggests feasible solutions to increase the welfare of these macaques. In the study, the early life history of the animal and the lack of social and environmental stimulus could be very critical for the development of behavioral pathogens. However, to establish this would require more research.
The P300 as marker of inhibitory control – fact or fiction?
Authors: Huster René J. , Messel Mari S. , Thunberg Christina , Raud Liisa 
Published: July 2019

AbstractInhibitory control, i.e., the ability to stop or suppress actions, thoughts, or memories, represents a prevalent and popular concept in basic and clinical neuroscience as well as psychology. At the same time, it is notoriously difficult to study as successful inhibition is characterized by the absence of a continuously quantifiable direct behavioral marker. It has been suggested that the P3 latency, and here especially its onset latency, may serve as neurophysiological marker of inhibitory control as it correlates with the stop signal reaction time (SSRT). The SSRT estimates the average stopping latency, which itself is unobservable since no overt response is elicited in successful stop trials, based on differences in the distribution of go reaction times and the delay of the stop- relative to the go-signal in stop trials.In a meta-analysis and an independent EEG experiment, we found that correlations between the P3-latency and the SSRT are indeed replicable, but also unspecific. Not only does the SSRT also correlate with the N2-latency, but both P3- and N2-latency measures show similar or even higher correlations with other behavioral parameters such as the go reaction time or stopping accuracy. The missing specificity of P3-SSRT correlations, together with the general pattern of associations, suggests that these manifest effects are driven by underlying latent processes other than inhibition, such as those associated with the speed-accuracy trade-off.
Maintenance of cell type-specific connectivity and circuit function requires Tao kinase
Authors: Tenedini Federico Marcello , González Maria Sáez , Hu Chun , Pedersen Lisa Hedegaard , Petruzzi Mabel Matamala , Spitzweck Bettina , Wang Denan , Richter Melanie , Petersen Meike , Szpotowicz Emanuela , Schweizer Michaela , Sigrist Stephan , de Anda Froylan Calderon , Soba Peter 
Published: July 2019

AbstractSensory circuits are typically established during early development, yet how circuit specificity and function are maintained during organismal growth has not been elucidated. To gain insight we quantitatively investigated synaptic growth and connectivity in theDrosophilanociceptive network during larval development. We show that connectivity between primary nociceptors and their downstream neurons scales with animal size. We further identified the conserved Ste20-like kinase Tao as a negative regulator of synaptic growth required for maintenance of circuit specificity and connectivity. Loss of Tao kinase resulted in exuberant postsynaptic specializations and aberrant connectivity during larval growth. Using functional imaging and behavioral analysis we show that loss of Tao-induced ectopic synapses with inappropriate partner neurons are functional and alter behavioral responses in a connection-specific manner. Our data show that fine-tuning of synaptic growth by Tao kinase is required for maintaining specificity and behavioral output of the neuronal network during animal growth.