bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comparison of Angiogenesis and Glycolytic Imaging in Patients With Clinical Suspected Locally Advanced Breast Cancer
Authors: Vatsa Rakhee , Ashwathanarayana Abhiram Gopalajois , Singh Gurpreet , Kavanal Anwin Joseph , Kumar Sunil , Rana Nivedita , Shukla Jaya , Mittal Bhagwant Rai
Published: June 2019

18F-FDG PET/CT imaging is an important diagnostic tool for accurate staging and assessment of response to neoadjuvant chemotherapy (NACT) in patients with locally advanced breast carcinoma (LABC). However, 18F-FDG being non-specific marker, it also accumulates in inflammatory conditions, leading to false positive results. Angiogenesis, an essential characteristic for tumor development, intrusion and metastasis can be imaged using 68Ga-labeled RGD tripeptide. We here depict a series of clinically staged LABC patients who underwent both 68Ga-DOTA-RGD2 and 18F-FDG PET/CT imaging for staging and illustrate the similarities and significant differences between the two tracers.
Diffusely Decreased Liver Uptake on FDG PET and Cancer-Associated Cachexia With Reduced Survival
Authors: Nakamoto Ryusuke , Okuyama Chio , Ishizu Koichi , Higashi Tatsuya , Takahashi Masaaki , Kusano Kuninori , Kagawa Shinya , Yamauchi Hiroshi
Published: June 2019

Objectives

We investigated clinical characteristics of patients with extremely increased or decreased physiologic 18F-FDG uptake of the liver and their prognosis.

Methods

One thousand four hundred eighty-seven PET/CT scans of patients with known or suspected malignancy were retrospectively analyzed. A spherical volume of interest (3 cm in diameter) was set on the right lobe of the liver to calculate the SUVmean. Scans with extremely high (SUVmean >97.5th percentile) and low (SUVmean <2.5th percentile) FDG uptake in the liver were evaluated. Physical and laboratory data among a control group (n = 30), the extremely high liver uptake group (HG, n = 36), and the extremely low liver uptake group (LG, n = 36) were compared. Overall survival (OS) of the 3 groups was also compared.

Results

Body weight and body mass index in the HG (SUVmean ≥3.04) were significantly higher than those in the control group. The LG cases (SUVmean ≤1.78) had anemia, impaired liver function, and systemic inflammation. They were also in a poor nutritional state. The characteristics of LG cases had many things in common with those of cachectic patients. Indeed, 36.1% of LG cases met the diagnostic criteria for cachexia. Moreover, in LG cases with viable and/or recurrent malignant lesions on FDG PET, the proportion of cachexia increased by 52.6%. The OS of LG cases (median, 33 months) was significantly worse than that of controls and HG cases.

Conclusions

Our data indicate that cancer patients with extremely decreased liver FDG uptake were likely to have cancer cachexia and a lower OS.
Hyperbaric Oxygen Therapy: An Effective and Noninvasive Therapy for Complications of Ear Reconstruction
Authors: Xu Feng , Zhang Ruhong , Zhang Qun , Xu Zhicheng , Li Datao , Li Yiyuan
Published: June 2019

Objectives:

Although complications of ear reconstruction are rare, common salvage procedures involve invasive surgery, and final outcomes can be uncertain. In this study, the authors have successfully applied noninvasive hyperbaric oxygen therapy (HBOT) as an adjunct treatment for the complications of ear reconstruction.

Methods:

During a 2-year period, 42 patients with complications of ear reconstruction were included in the study. All patients received HBOT twice a day for 2 to 3 courses, and each course lasted for 10 days.

Results:

Patients suffered from 4 different complications: hematoma (15), flap venous congestion (13), frame exposure (10), and postoperative infection (4). After HBOT, 41 patients recovered without a need for additional surgical repair. One patient developed an infection and required further treatment.

Conclusions:

Combined with traditional salvage procedures, HBOT effectively treated various complications of ear reconstruction.
Treatment of Difficult Minor Papilla Cannulation in Patients of Pancreatic Divisum: Using Endoscopic Ultrasonography–guided Puncture Combined With Endoscopic Retrograde Cholangiopancreatography: 2 Cases and Literature Review
Authors: Huang Pingxiao , Di Shujie , Fan Yan , Wang Jian , Zhang Heng , Wu Jie
Published: June 2019

Context:

Pancreas divisum (PD), the most common congenital anatomic variation of the pancreatic ductal system, is still rare in clinical practice. Endoscopic retrograde cholangiopancreatography (ERCP) is the first-line treatment for patients with symptomatic PD. However, even by experienced endoscopists, the procedure of ERCP can fail in 3% to 10% of cases. Traditionally, if we fail in cannulation we have no choice but to rely on surgery.

Case Report:

The 2 case reports of PD in this study with cannulation were both unsuccessful, fortunately, the use of endoscopic ultrasonography–guided pancreatic duct puncture combined with ERCP was eventually successful in treatment.

Conclusions:

Using endoscopic ultrasonography–guided pancreatic duct puncture combined with ERCP is safe and effective for the treatment of the patients of difficult minor papilla cannulation in patients of PD, and can be used as a remedy for minor papilla cannulation failure.
Adenosine, lidocaine, and Mg2+ fluid therapy leads to 72-hour survival after hemorrhagic shock: A model for studying differential gene expression and extending biological time
Authors: Letson Hayley Louise , Morris Jodie Lee , Biros Erik , Dobson Geoffrey Phillip
Published: June 2019

BACKGROUND

Noncompressible torso hemorrhage is a leading cause of traumatic death. Our aim was to examine survival time and the expression of key master genes of cellular metabolism after 3% NaCl adenosine, lidocaine, and Mg2+ (ALM) bolus and 4 hours 0.9% NaCl/ALM “drip” in a rat model of uncontrolled hemorrhagic shock.

METHODS

Male Sprague-Dawley rats (425 ± 8 g) were anesthetized and randomly assigned to saline controls (n = 10) or ALM therapy (n = 10). Hemorrhage was induced by liver resection (60% left lateral lobe). After 15 minutes, a single intravenous bolus of 3% NaCl ± ALM (0.7 mL/kg) was administered (Phase 1), and after 60 minutes, a 0.9% NaCl ± ALM stabilization “drip” (0.5 mL/kg per hour) was infused for 4 hours (Phase 2) with 72 hours monitoring. Mean arterial pressure and lactate were measured. After 72 hours (or high moribund score), tissues were freeze-clamped and stored at −80°C. Total RNA was extracted in heart, brain, and liver, and the relative expressions of amp-k, mtCO3, PGC-1α, and sirt-1 genes were determined.

RESULTS

Kaplan-Meier survival curves showed that controls had a mean survival time of 22.6 ± 4.5 hours, and ALM animals, 72 ± 0 hours (p < 0.05). Death in controls was accompanied by approximately sevenfold increase in lactate, while ALM animals maintained lactates similar to baseline over 72 hours. The relative expression of amp-k, PGC-1α, and sirt-1 in heart and brain was 1.5-fold and 2.7-fold higher in the ALM group compared with controls (p < 0.05), with the exception of mitochondrial encoded cytochrome C oxidase III pseudogene 1 in heart, which was 19-fold higher. In contrast, amp-k, sirt-1, and mtCO3 gene expression in liver was significantly 29–41% lower in the ALM group compared with controls, and PGC-1α was 75% lower.

CONCLUSION

Small-volume ALM therapy led to 3.3-times longer survival time compared with saline controls after hemorrhagic shock. A hallmark of the ALM-survival phenotype in heart and brain was an upregulation of amp-k, PGC-1α, sirt-1, and mtCO3 to presumably “boost” mitochondrial function and ATP production, and a contrasting downregulation in liver. These central-peripheral differences in gene expression require further investigation.
Pre-Border Gene Foxb1 Regulates the Differentiation Timing and Autonomic Neuronal Potential of Human Neural Crest Cells
Authors: Leung Alan W. , López-Giráldez Francesc , Broton Cayla , Lin Kaixuan , Prasad Maneeshi S. , Hernández Jacqueline C. , Xiao Andrew Z. , Garcia-Castro Martín I.
Published: June 2019

What are the factors that are induced during the transitory phases from pluripotent stem cells to lineage specified cells, how are they regulated, and what are their functional contributions are fundamental questions for basic developmental biology and clinical research. Here, we uncover a set of pre-border (pB) gene candidates, including forkhead box B1 (FOXB1), induced during human neural crest (NC) cell development. We characterize their associated enhancers that are bound by pluripotency factors and rapidly activated by β-catenin-mediated signaling during differentiation. Surprisingly, the endogenous transient expression of FOXB1 directly regulates multiple early NC and neural progenitor loci includingPAX7,MSX2,SOX1, andASCL1, controls the timing of NC fate acquisition, and differentially activates autonomic neurogenic versus mesenchymal fates in mature NC cells. Our findings provide further insight into the concept of the less characterized pB state and clearly establishes FOXB1 as a key regulator in early cell fate decisions during human pluripotent stem cell differentiation.
HiNT: a computational method for detecting copy number variations and translocations from Hi-C data
Authors: Wang Su , Lee Soohyun , Chu Chong , Jain Dhawal , Nelson Geoff , Walsh Jennifer M. , Alver Burak H. , Park Peter J.
Published: June 2019

The three-dimensional conformation of a genome can be profiled using Hi-C, a technique that combines chromatin conformation capture with high-throughput sequencing. However, structural variations (SV) often yield features that can be mistaken for chromosomal interactions. Here, we describe a computational method HiNT (Hi-C for copy Number variation and Translocation detection), which detects copy number variations and inter-chromosomal translocations within Hi-C data with breakpoints at single base-pair resolution. We demonstrate that HiNT outperforms existing methods on both simulated and real data. We also show that Hi-C can supplement whole-genome sequencing in SV detection by locating breakpoints in repetitive regions.
Familial t(1;11) translocation is associated with disruption of white matter structural integrity and oligodendrocyte-myelin dysfunction
Authors: Vasistha Navneet A. , Johnstone Mandy , Barton Samantha K. , Mayerl Steffen , Selvaraj Bhuvaneish T. , Thomson Pippa A , Dando Owen , Grünewald Ellen , Alloza Clara , Bastin Mark E. , Livesey Matthew R. , Economides Kyriakos , Magnani Dario , Makedonopolou Paraskevi , Burr Karen , Story David J. , Blackwood Douglas J. , Wyllie David J.A , McIntosh Andrew M. , Kirsty Millar J. , ffrench-Constant Charles , Hardingham Giles E. , Lawrie Stephen M. , Chandran Siddharthan
Published: June 2019

Although the underlying neurobiology of major mental illness (MMI) remains unknown, emerging evidence implicates a role for oligodendrocyte-myelin abnormalities. Here, we took advantage of a large family carrying a balanced t(1;11) translocation, which substantially increases risk of MMI, to undertake both diffusion tensor imaging (DTI) and cellular studies to evaluate the consequences of the t(1;11) translocation on white matter structural integrity and oligodendrocyte-myelin biology. This translocation disrupts among others theDISC1gene which plays a crucial role in brain development. We show that translocation-carrying patients display significant disruption in white matter integrity compared to familial controls. At a cellular level, we observe dysregulation of key pathways controlling oligodendrocyte development and morphogenesis in induced pluripotent stem cell (iPSC) case derived oligodendrocytes. This is associated with reduced proliferation and a stunted morphologyin vitro. Further, myelin internodes in a humanized mouse model that recapitulates the human translocation as well as after transplantation of t(1;11) oligodendrocyte progenitors were significantly reduced compared to controls. Thus we provide evidence that the t(1;11) translocation has biological effects at both the systems and cellular level that together suggest oligodendrocyte-myelin dysfunction.
Diminished cortical excitation and elevated inhibition during perceptual impairments in a mouse model of autism
Authors: Rosario Joseph Del , Speed Anderson , Arrowood Hayley , Motz Cara , Pardue Machelle , Haider Bilal
Published: June 2019

Sensory impairments are a core feature of autism spectrum disorder (ASD). These impairments affect visual perception (Robertson and Baron-Cohen, 2017), and have been hypothesized to arise from imbalances in cortical excitatory and inhibitory activity (Rubenstein and Merzenich, 2003; Nelson and Valakh, 2015; Sohal and Rubenstein, 2019); however, there is little direct evidence testing this hypothesis in identified excitatory and inhibitory neurons during impairments of sensory perception. Several recent studies have examined cortical activity in transgenic mouse models of ASD (Goel et al., 2018; Antoine et al., 2019; Lazaro et al., 2019), but have provided conflicting evidence for excitatory versus inhibitory activity deficits. Here, we utilized a genetically relevant mouse model of ASD (CNTNAP2−/− knockout, KO; Arking et al., 2008; Penagarikano et al., 2011) and directly recorded putative excitatory and inhibitory population spiking in primary visual cortex (V1) while measuring visual perceptual behavior (Speed et al., 2019). We found quantitative impairments in the speed, accuracy, and contrast sensitivity of visual perception in KO mice. These impairments were simultaneously associated with elevated inhibitory and diminished excitatory neuron activity evoked by visual stimuli during behavior, along with aberrant 3 – 10 Hz oscillations in superficial cortical layers 2/3 (L2/3). These results establish that perceptual deficits relevant for ASD can arise from diminished sensory activity of excitatory neurons in feedforward layers of cortical circuits.
Spatially resolved dendritic integration: Towards a functional classification of neurons
Authors: Kirch Christoph , Gollo Leonardo L
Published: June 2019

The vast tree-like dendritic structure of neurons allows them to receive and integrate input from many neurons. A wide variety of neuronal morphologies exist, however, their role in dendritic integration, and how it shapes the response of the neuron, is not yet fully understood. Here, we study the evolution and interactions of dendritic spikes in excitable neurons with complex real branch structures. We focus on dozens of digitally reconstructed illustrative neurons from the online repository NeuroMorpho.org, which contains over 100,000 neurons. Yet, our methods can be promptly extended to any other neuron. This approach allows us to estimate and map specific and heterogeneous patterns of activity observed across extensive dendritic trees with thousands of compartments. We propose a classification of neurons based on the location of the soma (centrality) and the number of branches connected to the soma. These are key topological factors in determining the neuron’s energy consumption, firing rate, and the dynamic range, which quantifies the range in synaptic input rate that can be reliably encoded by the neuron’s firing rate. Moreover, we find that bifurcations, the structural building blocks of complex dendrites, play a major role in increasing the dynamic range of neurons. Our results provide a better understanding of the effects of neuronal morphology in the diversity of neuronal dynamics and function.
Inference of bacterial small RNA regulatory networks and integration with transcription factor driven regulatory networks
Authors: Arrieta-Ortiz Mario L. , Hafemeister Christoph , Shuster Bentley , Baliga Nitin S. , Bonneau Richard , Eichenberger Patrick
Published: June 2019

Small non-coding RNAs (sRNAs) are key regulators of bacterial gene expression. Through complementary base pairing, sRNAs affect messenger RNA stability and translation efficiency. Here, we describe a network inference approach designed to identify sRNA-mediated regulation of transcript levels. We use existing transcriptional datasets and prior knowledge to infer sRNA regulons using our network inference tool, theInferelator. This approach produces genome-wide gene regulatory networks that include contributions by both transcription factors and sRNAs. We show the benefits of estimating and incorporating sRNA activities into network inference pipelines. We comprehensively assess the accuracy of inferred sRNA regulons using available experimental data. We uncover 30 novel experimentally supported sRNA-mRNA interactions inEscherichia coli, outperforming previous network-based efforts. Our findings expand the role of sRNAs in the regulation of chemotaxis, oxidation-reduction processes, galactose intake, and generation of pyruvate. Additionally, our pipeline complements sequence-based sRNA-mRNA interaction prediction methods by adding a data-driven filtering step. Finally, we show the general applicability of our approach by identifying novel, experimentally supported, sRNA-mRNA interactions inPseudomonas aeruginosaandBacillus subtilis. Overall, our strategy generates novel insights into the functional implications of sRNA regulation in multiple bacterial species.

IMPORTANCE

Individual bacterial genomes can have dozens of small non-coding RNAs with largely unexplored regulatory functions. Although bacterial sRNAs influence a wide range of biological processes, including antibiotic resistance and pathogenicity, our current understanding of sRNA-mediated regulation is far from complete. Most of the available information is restricted to a few well-studied bacterial species; and even in those species, only partial sets of sRNA targets have been characterized in detail. To close this information gap, we developed a computational strategy that takes advantage of available transcriptional data and knowledge about validated and putative sRNA-mRNA interactions. Our approach facilitates the identification of experimentally supported novel interactions while filtering out false positives. Due to its data-driven nature, our method emerges as an ideal strategy to identify biologically relevant interactions among lists of candidate sRNA-target pairs predictedin silicofrom sequence analysis or derived from sRNA-mRNA binding experiments.
FAIRshake: toolkit to evaluate the findability, accessibility, interoperability, and reusability of research digital resources
Authors: Clarke Daniel J. B. , Wang Lily , Jones Alex , Wojciechowicz Megan L. , Torre Denis , Jagodnik Kathleen M. , Jenkins Sherry L. , McQuilton Peter , Flamholz Zachary , Silverstein Moshe C. , Schilder Brian M. , Robasky Kimberly , Castillo Claris , Idaszak Ray , Ahalt Stanley C. , Williams Jason , Schurer Stephan , Cooper Daniel J. , de Miranda Azevedo Ricardo , Klenk Juergen A. , Haendel Melissa A. , Nedzel Jared , Avillach Paul , Shimoyama Mary E. , Harris Rayna M. , Gamble Meredith , Poten Rudy , Charbonneau Amanda L. , Larkin Jennie , Brown C. Titus , Bonazzi Vivien R. , Dumontier Michel J. , Sansone Susanna-Assunta , Ma’ayan Avi
Published: June 2019

As more datasets, tools, workflows, APIs, and other digital resources are produced by the research community, it is becoming increasingly difficult to harmonize and organize these efforts for maximal synergistic integrated utilization. The Findable, Accessible, Interoperable, and Reusable (FAIR) guiding principles have prompted many stakeholders to consider strategies for tackling this challenge by making these digital resources follow common standards and best practices so that they can become more integrated and organized. Faced with the question of how to make digital resources more FAIR, it has become imperative to measure what it means to be FAIR. The diversity of resources, communities, and stakeholders have different goals and use cases and this makes assessment of FAIRness particularly challenging. To begin resolving this challenge, the FAIRshake toolkit was developed to enable the establishment of community-driven FAIR metrics and rubrics paired with manual, semi- and fully-automated FAIR assessment capabilities. The FAIRshake toolkit contains a database that lists registered digital resources, with their associated metrics, rubrics, and assessments. The FAIRshake toolkit also has a browser extension and a bookmarklet that enables viewing and submitting assessments from any website. The FAIR assessment results are visualized as an insignia that can be viewed on the FAIRshake website, or embedded within hosting websites. Using FAIRshake, a variety of bioinformatics tools, datasets listed on dbGaP, APIs registered in SmartAPI, workflows in Dockstore, and other biomedical digital resources were manually and automatically assessed for FAIRness. In each case, the assessments revealed room for improvement, which prompted enhancements that significantly upgraded FAIRness scores of several digital resources.
Affective Pavlovian motivation is enhanced in obesity susceptible populations; implications for incentive motivation in obesity
Authors: Derman Rifka C. , Ferrario Carrie R.
Published: June 2019

Global obesity rates continue to rise, presenting a major challenge to human health. Efforts to uncover the drivers of this epidemic have highlighted the contribution of Pavlovian motivational processes to overeating. In humans, brain and behavioral reactivity to food related stimuli positively correlates with subsequent weight gain. In concordance with this, selectively bred obesity-prone rats exhibit stronger cue-triggered food-seeking via single outcome Pavlovian-to-instrumental transfer (SO PIT) than obesity-resistant rats. These data show that Pavlovian motivation is stronger in selectively bred obesity-prone groups. However, whether obesity susceptibility in outbred populations is associated with enhanced PIT is unknown. Moreover, PIT can arise via two neurobehaviorally dissociable processes, a sensory specific versus a general affective process that cannot be distinguished by SO PIT. Thus, it is unclear which PIT process is enhanced in obesity-prone groups. Therefore, we determined whether obesity susceptibility in outbred populations is associated with enhanced Sensory Specific (SS) PIT or General PIT and whether expression of these forms of PIT differs between selectively bred obesity-prone versus obesity-resistant rats. We find that in outbred rats, the magnitude of General PIT is positively correlated with subsequently determined obesity susceptibility. In selectively bred rats, the magnitude of General PIT was stronger in obesity-prone versus obesity-resistant groups. Jointly, these data show that enhanced affective Pavlovian motivation is tightly linked to obesity vulnerability, supporting a role for phenotypic differences in incentive motivation for the development of obesity. This has important implications for obesity prevention and for understanding the neurocircuitry mediating enhanced food-seeking in vulnerable individuals.
Action information contributes to metacognitive decision-making
Authors: Wokke Martijn E. , Achoui Dalila , Cleeremans Axel
Published: June 2019

Monitoring and control of our decision process are key ingredients of adept decision-making. Such metacognitive abilities allow us to adjust ongoing behavior and modify future decisions in the absence of external feedback. Although metacognition is critical in many daily life settings, it remains unclear what information is actually being monitored and what kind of information is being used for metacognitive decisions. In the present study, we investigated whether response information connected to perceptual events contribute to metacognitive decision-making. Therefore, we recorded EEG signals during a perceptual color discrimination task while participants were asked to provide an estimate about the quality of their decision on each trial. Critically, the moment participants provided second-order decisions varied across conditions, thereby changing the amount of action information (e.g., response competition or response fluency) available for metacognitive decisions.

Results from three experiments demonstrate that metacognitive performance improved when first-order action information was available at the moment metacognitive decisions about the perceptual task had to be provided. This behavioral effect was accompanied by enhanced functional connectivity (beta phase synchrony) between motor areas and prefrontal regions, exclusively observed during metacognitive decision-making. Our findings demonstrate that action information contributes to metacognitive decision-making, thereby painting a picture of metacognition as a second-order process, integrating sensory evidence and the state of the decider during decision-making.

Significance

Monitoring and control of our decision process is a critical part of every day decision-making. When feedback is not available, metacognitive skills enable us to modify current behavior and adapt prospective decision-making. Here, we investigated what kind information is being used to compute an estimate about the quality of our decisions. Results demonstrate that during perceptual decision-making, information about one’s actions towards perceptual events is being used to evaluate the quality of one’s decisions. EEG results indicate that functional connectivity between motor regions and prefrontal cortex could serve as a mechanism to convey action information during metacognitive decision-making. Considered together, our results demonstrate that post-decisional information contributes to metacognition, thereby evaluating not only what one perceives (e.g., strength of perceptual evidence) but also how one responds towards perceptual events.
ARA: accurate, reliable and active histopathological image classification framework with Bayesian deep learning
Authors: Rączkowski Łukasz , Możejko Marcin , Zambonelli Joanna , Szczurek Ewa
Published: June 2019

Machine learning algorithms hold the promise to effectively automate the analysis of histopathological images that are routinely generated in clinical practice. Any machine learning method used in the clinical diagnostic process has to be extremely accurate and, ideally, provide a measure of uncertainty for its predictions. Such accurate and reliable classifiers need enough labelled data for training, which requires time-consuming and costly manual annotation by pathologists. Thus, it is critical to minimise the amount of data needed to reach the desired accuracy by maximising the efficiency of training. We propose an accurate, reliable and active (ARA) image classification framework and introduce a new Bayesian Convolutional Neural Network (ARA-CNN) for classifying histopathological images of colorectal cancer. The model achieves exceptional classification accuracy, outperforming other models trained on the same dataset. The network outputs an uncertainty measurement for each tested image. We show that uncertainty measures can be used to detect mislabelled training samples and can be employed in an efficient active learning workflow. Using a variational dropout-based entropy measure of uncertainty in the workflow speeds up the learning process by roughly 45%. Finally, we utilise our model to segment whole-slide images of colorectal tissue and compute segmentation-based spatial statistics.
Linking genotypes with multiple phenotypes in single-cell CRISPR screens
Authors: Yang Lin , Zhu Yuqing , Yu Hua , Chen Sitong , Chu Yulan , Huang He , Zhang Jin , Li Wei
Published: June 2019

CRISPR/Cas9 based functional screening coupled with single-cell RNA-seq (“single-cell CRISPR screening”) unravels gene regulatory networks and enhancer-gene regulations in a large scale. We propose scMAGeCK, a computational framework to systematically identify genes and non-coding elements associated with multiple expression-based phenotypes in single-cell CRISPR screening. scMAGeCK identified genes and enhancers that modulate the expression of a known proliferation marker, MKI67 (Ki-67), a result that resembles the outcome of proliferation-linked CRISPR screening. We further performed single-cell CRISPR screening on mouse embryonic stem cells (mESC), and identified key genes associated with different pluripotency states. scMAGeCK enabled an unbiased construction of genotype-phenotype network, where multiple phenotypes can be regulated by different gene perturbations. Finally, we studied key factors that improve the statistical power of single-cell CRISPR screens, including target gene expression and the number of guide RNAs (gRNAs) per cell. Collectively, scMAGeCK is a novel and effective computational tool to study genotype-phenotype relationships at a single-cell level.
Temporal dynamics of Bacteria, Archaea and protists in equatorial coastal waters
Authors: Chénard Caroline , Wijaya Winona , Vaulot Daniel , dos Santos Adriana Lopes , Martin Patrick , Kaur Avneet , Lauro Federico M
Published: June 2019

Singapore, an equatorial island in South East Asia, is influenced by a bi-annual reversal of wind directions which defines two monsoon seasons. We characterized the dynamics of the microbial communities of Singapore coastal waters by collecting monthly samples between February 2017 and July 2018 at four sites located across two straits with different trophic status, and sequencing the V6-V8 region of the small sub-unit ribosomal RNA gene (rRNA gene) of Bacteria, Archaea, and Eukaryota. Johor Strait, which is subjected to wider environmental fluctuations from anthropogenic activities, presented a higher abundance of copiotrophic microbes, including Cellvibrionales and Rhodobacterales. The mesotrophic Singapore Strait, where the seasonal variability is caused by changes in the oceanographic conditions, harboured a higher proportion of typically marine microbe groups such as Synechococcales, Nitrosupumilales, SAR11, SAR86, Marine Group II Archaea and Radiolaria. In addition, we observed seasonal variability of the microbial communities in the Singapore Strait, which was possibly influenced by the alternating monsoon regime, while no seasonal pattern was detected in the Johor Strait.
Axial variation of deoxyhemoglobin density as a source of the low-frequency time lag structure in blood oxygenation level-dependent signals
Authors: Aso Toshihiko , Urayama Shinnichi , Hidenao Fukuyama , Murai Toshiya
Published: June 2019

Perfusion-related information is reportedly embedded in the low-frequency component of a blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signal. The blood-propagation pattern through the cerebral vascular tree is detected as an interregional lag variation of spontaneous low-frequency oscillations (sLFOs). Mapping of this lag, or phase, has been implicitly treated as a projection of the vascular tree structure onto real space. While accumulating evidence supports the biological significance of this signal component, the physiological basis of the “perfusion lag structure,” a requirement for an integrative resting-state fMRI-signal model, is lacking. In this study, we conducted analyses furthering the hypothesis that the sLFO is not only largely of systemic origin, but also essentially intrinsic to blood, and hence behaves as a virtual tracer. By summing the small fluctuations of instantaneous phase differences between adjacent vascular regions, a velocity response to respiratory challenges was detected. Regarding the relationship to neurovascular coupling, the removal of the whole lag structure, which can be considered as an optimized global-signal regression, resulted in a reduction of inter-individual variance while preserving the fMRI response. Examination of the T2* and S0, or non-BOLD, components of the fMRI signal revealed that the lag structure is deoxyhemoglobin dependent, while paradoxically presenting a signal-magnitude reduction in the venous side of the cerebral vasculature. These findings provide insight into the origin of BOLD sLFOs, suggesting that they are highly intrinsic to the circulating blood.
Tooth Fracture Frequency in Gray Wolves Reflects Prey Availability
Authors: Van Valkenburgh Blaire , Peterson Rolf O. , Smith Douglas W. , Stahler Daniel R. , Vucetich John A.
Published: June 2019

Exceptionally high rates of tooth fracture in large Pleistocene carnivorans imply intensified interspecific competition, given that tooth fracture rises with increased bone consumption, a behavior that likely occurs when prey are difficult to acquire. To assess the link between prey availability and dental attrition, we documented dental fracture rates over decades among three well-studied populations of extant gray wolves that differed in prey:predator ratio and levels of carcass utilization. When prey:predator ratios declined, kills were more fully consumed, and rates of tooth fracture more than doubled. This supports tooth fracture frequency as a relative measure of the difficulty of acquiring prey, and reveals a rapid response to diminished food levels in large carnivores despite risks of infection and reduced fitness due to dental injuries. More broadly, large carnivore tooth fracture frequency likely reflects energetic stress, an aspect of predator success that is challenging to quantify in wild populations.
Cytotoxicity of 1-deoxysphingolipid Unraveled by Genome-wide Genetic Screens and Lipidomics
Authors: Haribowo A. Galih , Hannich J. Thomas , Michel Agnès H. , Megyeri Márton , Schuldiner Maya , Kornmann Benoît , Riezman Howard
Published: June 2019

Hereditary Sensory and Autonomic Neuropathy (HSAN) type IA and IC are caused by elevated levels of an atypical class of lipid named 1-deoxysphingolipid (DoxSL). How elevated levels of DoxSL perturb the physiology of the cell and how the perturbations lead to HSAN IA/C are largely unknown. In this study, we show that C26-1-deoxydihydroceramide (C26-DoxDHCer) is highly toxic to the cell, while C16- and C18-DoxDHCer are less toxic. Genome-wide genetic screens and lipidomics revealed the dynamics of DoxSL accumulation and DoxSL species responsible for the toxicity over the course of DoxSL accumulation. Furthermore, we show that disruption of F-actin organization, alteration of mitochondrial shape, and accumulation of hydrophobic bodies by DoxSL are not sufficient to cause complete cellular failure. However, combined with collapsed ER membrane, these perturbations cause cell death. Thus, we have unraveled key principles of DoxSL cytotoxicity that help to explain the clinical features of HSAN IA/C.
Social, demographic, health care and co-morbidity predictors of tuberculosis mortality in Amazonas, Brazil: a multiple cause of death approach
Authors: de Souza Sampaio Vanderson , Ferreira da Silva Leila Cristina , de Castro Daniel Barros , da Silva Balieiro Patrícia Carvalho , Cabrinha Ana Alzira , Leal Costa Antonio José
Published: June 2019

OBJECTIVES

To estimate TB mortality rates, describe multiple causes in death certificates in which TB was reported and identify predictors of TB reporting in death certificates in the State of Amazonas, Brazil, based on a multiple cause of death approach.

METHODS

Death records of residents in AM within 2006-2014 were classified based on tuberculosis reporting in the death certificate as tuberculosis not reported (TBNoR), reported as the underlying cause of death (TBUC) and as an associate cause of death (TBAC). Age standardized annual mortality rates for TBUC, TBAC and with TB reported (TBUC plus TBAC) were estimated for the State of Amazonas, using the direct standardization method and WHO 2000-2025 standard population. Mortality odds ratios (OR) of reporting TBUC and TBAC were estimated using multinomial logistic regression.

RESULTS

Age standardized annual TBUC and TBAC mortality rates ranged, between 5.9-7.8/105 and 2.7-4.0/105, respectively. TBUC was associated with residence in the State capital (OR=0.66), female sex (OR=0.87), education level (OR=0.67 and 0.50 for 8 to 11 and 12 or more school years), non-white race/skin colour (OR=1.38) and occurrence of death in the State capital (OR=1.69). TBAC was related to time (OR=1.21 and 1.22 for years 2009-11 and 2012-14), age (OR=36.1 and 16.5 for ages 15-39 and 40-64 years) and when death occurred in the State capital (OR=5.8).

CONCLUSION

TBUC was predominantly associated with indicators of unfavorable socioeconomic conditions and health care access constraints, whereas TBAC was mainly related to ages typical of high HIV disease incidence.

Conflicts of interest

None.

Funding

Fundação de Amparo à Pesquisa do Estado do Amazonas - FAPEAM
Partial Jacobsen syndrome phenotype in a patient with a de novo frameshift mutation in the ETS1 transcription factor
Authors: Tootleman Eva , Malamut Barbara , Akshoomoff Natacha , Mattson Sarah N. , Hoffman Hal M. , Jones Marilyn C. , Printz Beth , Shiryaev Sergey A. , Grossfeld Paul
Published: June 2019

Jacobsen syndrome (OMIM #147791) is a rare contiguous gene disorder caused by deletions in distal 11q. The clinical phenotype is variable and can include dysmorphic features, varying degrees of intellectual disability, behavioral problems including autism and attention deficit hyperactivity disorder, congenital heart defects, structural kidney defects, genitourinary problems, immunodeficiency, and a bleeding disorder due to impaired platelet production and function. Previous studies combining both human and animal systems have implicated several disease-causing genes in distal 11q that contribute to the Jacobsen syndrome phenotype. One gene, ETS1, has been implicated in causing congenital heart defects, structural kidney defects, and immunodeficiency. We performed a comprehensive phenotypic analysis on a patient with congenital heart disease previously found to have a de novo frameshift mutation in ETS1, resulting in the loss of the DNA-binding domain of the protein. Our results suggest that loss of Ets1 causes a “partial Jacobsen syndrome phenotype” including congenital heart disease, facial dysmorphism, intellectual disability, and attention deficit hyperactivity disorder.
Elucidating a false-negative MYC break-apart fluorescence in situ hybridization probe study by next-generation sequencing in a patient with high-grade B-cell lymphoma with IGH/MYC and IGH/BCL2 rearrangements
Authors: Peterson Jess F. , Pitel Beth A. , Smoley Stephanie A. , Vasmatzis George , Smadbeck James B. , Greipp Patricia T. , Ketterling Rhett P. , Macon William R. , Baughn Linda B.
Published: June 2019

The identification of MYC rearrangements in several mature B-cell neoplasms is critical for diagnostic and prognostic purposes. Commercially available fluorescence in situ hybridization (FISH) probe sets, including IGH/MYC dual-color dual-fusion (D-FISH) and MYC break-apart probes (BAPs), serve as the primary methodology utilized to detect MYC rearrangements. However, performing either IGH/MYC D-FISH or MYC BAP FISH studies in isolation has been reported to result in false-negative results because of the complex nature of 8q24 rearrangements involving the MYC gene region. We report a 60-yr-old male with newly diagnosed high-grade B-cell lymphoma with a negative MYC BAP study, but with positive BCL2 and BCL6 BAP studies. Per our current laboratory algorithm to concurrently interrogate the MYC gene region with both MYC BAP and IGH/MYC D-FISH probe sets, we performed IGH/MYC D-FISH studies and detected an IGH/MYC fusion. To further characterize the discrepant MYC results obtained by FISH, a next-generation sequencing strategy, mate-pair sequencing (MPseq), was performed and revealed a small insertion (∼200 kb) of the IGH locus downstream from the MYC gene that was undetectable by MYC BAP studies. This case highlights the importance of utilizing both IGH/MYC D-FISH and MYC BAP sets to detect potential cryptic MYC rearrangements and also demonstrates the power of MPseq to characterize complex structural rearrangements and copy-number abnormalities unappreciable by FISH.
A self-adaptive alignment strategy for large components based on dynamic compliance center
Authors: Du Fuzhou , Wen Ke , Yu Hao
Published: June 2019

Purpose

Aiming at the problems of geometric precision misalignment and unconsidered physical constraints between large components during the measurement-assisted assembly, a self-adaptive alignment strategy based on the dynamic compliance center (DCC) is proposed in this paper, using force information to guide alignment compliantly.

Design/methodology/approach

First, the self-adaptive alignment process of large components is described, and its geometrical and mechanical characteristics are analyzed based on six-dimensional force/torque (F/T). The setting method of DCC is studied and the areas of DCC are given. Second, the self-adaptive alignment platform of large components driven by the measured six-dimensional F/T is constructed. Based on this platform, the key supporting technologies, including principle of self-adaptive alignment, coordinate transfer, calculation of six-dimensional F/T and alignment process control, are illustrated.

Findings

Using the presented strategy, the position and orientation of large component is adjusted adaptively responding to measured six-dimensional F/T and the changes of contact states are consistent with the strategy. Through the setting of DCC, alignment process runs smoothly without jamming.

Practical implications

This strategy is applied to the alignment experiment of large components muff coupling. The experimental results show that the proposed alignment strategy is correct and effective and meets the real-time requirement.

Originality/value

This paper proposed a novel way to apply force information in large component self-adaptive alignment, and the setting method of DCC was presented to make the alignment process more feasible.
An adaptive ball-head positioning visual servoing method for aircraft digital assembly
Authors: Liu Hua , Zhu Weidong , Dong Huiyue , Ke Yinglin
Published: June 2019

Purpose

To gain accurate support for large aircraft structures by ball joints in aircraft digital assembly, this paper aims to propose a novel approach based on visual servoing such that the positioner’s ball-socket can automatically and adaptively approach the ball-head fixed on the aircraft structures.

Design/methodology/approach

Image moments of circular marker labeled on the ball-head are selected as visual features to control the three translational degrees of freedom (DOFs) of the positioner, where the composite Jacobian matrix is full rank. Kalman–Bucy filter is adopted for its online estimation, which makes the control scheme more flexible without system calibration. A combination of proportional control with sliding mode control is proposed to improve the system stability and compensate uncertainties of the system.

Findings

The ball-socket can accurately and smoothly reach its desired position in a finite time (50s). Positional deviations between the spherical centers of ball-head and ball-socket in theX-Yplane can be controlled within 0.05 mm which meets the design requirement.

Practical implications

The proposed approach has been integrated into the pose alignment system. It has shown great potential to be widely applied in the leading support for large aircraft structures in aircraft digital assembly.

Originality/value

An adaptive approach for accurate support of large aircraft structures is proposed, which possesses characteristics of high precision, high efficiency and excellent stability.
Track-based analysis for profile generation on globoidal cam in automatic tool changer of CNC machining center
Authors: Verma Kuldeep , Belokar R.M. , Verma Vinod Kumar , Ntalianis Klimis
Published: June 2019

Purpose

This paper aims to propose an elementary approach towards the measurement of a globoidal cam profile used in an automatic tool changer (ATC) of computer numerical control (CNC) machines.

Design/methodology/approach

A simple and unique online method has been designed for the profile metrology of the cam. This simple methodology will replace the traditional methodology of profile metrology of cam by coordinate measuring machine (CMM). A globoidal cam with an indexable turret and roller follower (rotating in an enclosed track) has been evaluated in our analysis. This analysis plays a significant role in the performance determination of the cam as well as the ATC of CNC machines.

Findings

A novel model has been designed and implemented to investigate the profile of a globoidal cam. The proposed methodology becomes an enhancement over the old methodology, i.e. measurement through CMM. Theoretical analysis and practical implementation prove the significance of the method.

Originality/value

An enhanced methodology to effectively measure the globoidal cam profile has been proposed. The practical implication of the proposed methodology remains for the CNC machine tool and ATC manufacturers. Finally, analytical explorations have been carried out to prove the validity of the proposal.
Using positive behavioural support (PBS) for STOMP medication challenge
Authors: Gerrard David , Rhodes Jennifer , Lee Ruth , Ling Jonathan
Published: June 2019

Purpose

The purpose of this paper is to investigate if positive behavioural support (PBS) can be an effective alternative to medication, and can aid medication reduction in people with a learning disability, autism or both who are prescribed psychotropic medication for behaviour thought to be challenging. STOMP is an initiative supported by NHS England which aims to reduce inappropriate prescribing of psychotropic medication, i.e. antipsychotics used for challenging behaviour in the absence of a documented mental health diagnosis. PBS has been described as the first line of intervention for behaviours which challenge, (NICE, 2015) and has been highlighted as a non-pharmacological alternative to, medication.

Design/methodology/approach

A two-group, experimental design was utilised. Both groups were considered for medication reduction. The experimental group of 25 people received input from a specialist PBS team, while the control group of 29 people underwent unsupported medication challenge.

Findings

There was a significantly higher success rate for medication reduction and discontinuation when PBS assessment and intervention was provided as an alternative to medication.

Practical implications

This study indicates that providing PBS is associated with decreased medication and if replicated should be become standard practice for specialist teams.

Originality/value

This is the first study to investigate the effect of PBS on medication reduction in patients prescribed psychotropic medication for behaviour thought to be challenging.
Fair value accounting, earnings management, and the case of bargain purchase gain
Authors: Lilien Steven , Sarath Bharat , Yan Yan
Published: June 2019

Purpose

The purpose of this paper is to investigate the association between bargain purchase gains (BPGs) booked by the acquirer and smoothing of acquirers’ earning performance across time.

Design/methodology/approach

The authors use a sample of 122 bargain purchase acquisitions in non-financial industries from 2009 to 2012 and a pair-match control group of 122 goodwill acquisitions.

Findings

The authors find that BPGs, and in particular, the Level-3 fair value estimates of intangible assets acquired, have consistently been used to smooth earnings but that such smoothing activities are not associated with long-term market returns.

Originality/value

This study is the first one to investigate bargain purchase acquisitions in a broad range of non-financial industries and suggests that managers are using the valuation of intangibles to avoid unfavorable earnings even though these valuations are not credible to investors.