Miracle-dz/UniFAR-FTUs huggingface dataset:
Approximate Subgraph Matching-Based Literature Mining for Biomedical Events and Relations

The biomedical text mining community has focused on developing techniques to automatically extract important relations between biological components and semantic events involving genes or proteins from literature. In this paper, we propose a novel approach for mining relations and events in the biomedical literature using approximate subgraph matching. Extraction of such knowledge is performed by searching for an approximate subgraph isomorphism between key contextual dependencies and input sentence graphs. Our approach significantly increases the chance of retrieving relations or events encoded within complex dependency contexts by introducing error tolerance into the graph matching process, while maintaining the extraction precision at a high level. When evaluated on practical tasks, it achieves a 51.12% F-score in extracting nine types of biological events on the GE task of the BioNLP-ST 2011 and an 84.22% F-score in detecting protein-residue associations. The performance is comparable to the reported systems across these tasks, and thus demonstrates the generalizability of our proposed approach.
The Adaptive Bleaching Hypothesis: Experimental Tests of Critical Assumptions

Coral bleaching, the loss of color due to loss of symbiotic zooxanthellae or their pigment, appears to be increasing in intensity and geographic extent, perhaps related to increasing sea surface temperatures. The adaptive bleaching hypothesis (ABH) posits that when environmental circumstances change, the loss of one or more kinds of zooxanthellae is rapidly, sometimes unnoticeably, followed by formation of a new symbiotic consortium with different zooxanthellae that are more suited to the new conditions in the host’s habitat. Fundamental assumptions of the ABH include (1) different types of zooxanthellae respond differently to environmental conditions, specifically temperature, and (2) bleached adults can secondarily acquire zooxanthellae from the environment. We present simple tests of these assumptions and show that (1) genetically different strains of zooxanthellae exhibit different responses to elevated temperature, (2) bleached adult hosts can acquire algal symbionts with an apparently dose-dependent relationship between the concentration of zooxanthellae and the rate of establishment of the symbiosis, (3) and finally, bleached adult hosts can acquire symbionts from the water column.
Comparison of 133 xenon ventilation equilibrium scan (XV) and 99m technetium transmission (TT) scan for use in regional lung analysis by 2D gamma scintigraphy in healthy and cystic fibrosis lungs.

BACKGROUND Quantification of particle deposition in the lung by gamma scintigraphy requires a reference image for location of regions of interest (ROIs) and normalization to lung thickness. In various laboratories, the reference image is made by a transmission scan ((57)Co or (99m)Tc) or gas ventilation scan ((133)Xe or (81)Kr). There has not been a direct comparison of measures from the two methods. METHODS We compared (99m)Tc transmission scans to (133)Xe equilibrium ventilation scans as reference images for 38 healthy subjects and 14 cystic fibrosis (CF) patients for their effects on measures of regional particle deposition: the central-to-peripheral ratio of lung counts (C/P); and ROI area versus forced vital capacity. Whole right lung ROI was based on either an isocontour threshold of three times the soft tissue transmission (TT) or a threshold of 20% of peak xenon ventilation counts (XV). We used a central ROI drawn to 50% of height and of width of the whole right lung ROI and placed along the left lung margin and centered vertically. RESULTS In general, the correlation of normalized C/P (nC/P) between the two methods was strong. However, the value of nC/P was significantly smaller for the XV method than the TT method. Regression equations for the relationship of nC/P between the two methods were, for healthy subjects, y=0.75x+0.61, R(2)=0.64 using rectangular ROIs and y=0.76x+0.45, R(2)=0.66 using isocontour ROIs; and for CF patients, y=0.94x+0.46, R(2)=0.43 and y=0.85x+0.42, R(2)=0.41, respectively. CONCLUSIONS (1) A transmission scan with an isocontour outline in combination with a rectangular central region to define the lung borders may be more useful than a ventilation scan. (2) Close correlation of nC/Ps measured by transmission or gas ventilation should allow confident comparison of values determined by the two methods.
Genetic Introgression: An Integral but Neglected Component of Speciation in Birds

The Auk, Vol. 128, Number 4, pages 620−632. ISSN 0004-8038, electronic ISSN 1938-4254.  2011 by The American Ornithologists’ Union. All rights reserved. Please direct all requests for permission to photocopy or reproduce article content through the University of California Press’s Rights and Permissions website, http://www.ucpressjournals. com/reprintInfo.asp. DOI: 10.1525/auk.2011. 128.4. 620 3E-mail: frankrheindt@yahoo.com. au Hybridization, or the act of reproduction between different species, is common in birds (Grant and Grant 1992) and can be an agent of adaptive evolution (Veen et al. 2001). When hybridization occurs, a species’ genetic material may enter the gene pool of another and thereby introduce genetic novelty. This process is called “genetic introgression” (hereafter “introgression”; Anderson 1949). Although known for decades, the incidence of introgression in nature has long been underappreciated (e.g., Currat et al. 2008). Only recently have evolutionists come to regard it as an important and pervasive mechanism in speciation, in the maintenance of genetic diversity and in the introduction of advantageous novelty into the gene pool (Arnold et al. 1999, Noor et al. 2000, Seehausen 2004). In fact, genetic data now suggest that our own species may have undergone a complicated history of introgression with at least two extinct hominine lineages (Green et al. 2010, Reich et al. 2010). Another reason why introgression is an important topic is the impact of human-induced climate change, which is rapidly shifting vegetation boundaries and creating new hybrid zones, with little-known consequences for the genetic integrity of species (Mank et al. 2004, Brumfield 2010). There has been a tremendous increase in introgressionrelated avian research since a comprehensive overview of the introgression complex between the Blue-winged Warbler (Vermivora cyanoptera) and the Golden-winged Warbler (V. chrysoptera) appeared in The Auk five years ago (Confer 2006). Here, we seek to fill a gap by summarizing the most important recent advances in avian introgression research and our current understanding of locus-specific differences in introgression dynamics, the detection of introgression, its directionality, and its relevance to conservation, phylogenetics, and speciation research.
Effects of Early-Life Adversity on Hippocampal Structures and Associated HPA Axis Functions

Early-life adversity (ELA) is one of the major risk factors for serious mental and physical health risks later in life. ELA has been associated with dysfunctional neurodevelopment, especially in brain structures such as the hippocampus, and with dysfunction of the stress system, including the hypothalamic-pituitary-adrenal (HPA) axis. Children who have experienced ELA are also more likely to suffer from mental health disorders such as depression later in life. The exact interplay of aberrant neurodevelopment and HPA axis dysfunction as risks for psychopathology is not yet clear. We investigated volume differences in the bilateral hippocampus and in stress-sensitive hippocampal subfields, behavior problems, and diurnal cortisol activity in 24 children who had experienced documented ELA (including out-of-home placement) in a circumscribed duration of adversity only in their first 3 years of life in comparison to data on 25 control children raised by their biological parents. Hippocampal volumes and stress-sensitive hippocampal subfields (Cornu ammonis [CA]1, CA3, and the granule-cell layer of the dentate gyrus [GCL-DG]) were significantly smaller in children who had experienced ELA, taking psychiatric diagnoses and dimensional psychopathological symptoms into account. ELA moderated the relationship between left hippocampal volume and cortisol: in the control group, hippocampal volumes were not related to diurnal cortisol, while in ELA children, a positive linear relationship between left hippocampal volume and diurnal cortisol was present. Our findings show that ELA is associated with altered development of the hippocampus, and an altered relationship between hippocampal volume and HPA axis activity in youth in care, even after they have lived in stable and caring foster family environments for years. Altered hippocampal development after ELA could thus be associated with a risk phenotype for the development of psychiatric disorders later in life.
Short Term Effects of Particle Exposure on Hospital Admissions in the Mid-Atlantic States: A Population Estimate

Background Many studies report significant associations between PM2.5 (particulate matter <2.5 micrometers) and hospital admissions. These studies mostly rely on a limited number of monitors which introduces exposure error, and excludes rural and suburban populations from locations where monitors are not available, reducing generalizability and potentially creating selection bias. Methods Using prediction models developed by our group, daily PM2.5 exposure was estimated across the Mid-Atlantic (Washington D.C., and the states of Delaware, Maryland, New Jersey, Pennsylvania, Virginia, New York and West Virginia). We then investigated the short-term effects of PM2.5 exposures on emergency hospital admissions of the elderly in the Mid-Atlantic region.We performed case-crossover analysis for each admission type, matching on day of the week, month and year and defined the hazard period as lag01 (a moving average of day of admission exposure and previous day exposure). Results We observed associations between short-term exposure to PM2.5 and hospitalization for all outcomes examined. For example, for every 10-µg/m3 increase in short-term PM 2.5 there was a 2.2% increase in respiratory diseases admissions (95% CI = 1.9 to 2.6), and a 0.78% increase in cardiovascular disease (CVD) admission rate (95% CI = 0.5 to 1.0). We found differences in risk for CVD admissions between people living in rural and urban areas. For every10-µg/m3 increase in PM 2.5 exposure in the ‘rural’ group there was a 1.0% increase (95% CI = 0.6 to 1.5), while for the ‘urban’ group the increase was 0.7% (95% CI = 0.4 to 1.0). Conclusions Our findings showed that PM2.5 exposure was associated with hospital admissions for all respiratory, cardio vascular disease, stroke, ischemic heart disease and chronic obstructive pulmonary disease admissions. In addition, we demonstrate that our AOD (Aerosol Optical Depth) based exposure models can be successfully applied to epidemiological studies investigating the health effects of short-term exposures to PM2.5.
Time Limits in Reinforcement Learning

In reinforcement learning, it is common to let an agent interact for a fixed amount of time with its environment before resetting it and repeating the process in a series of episodes. The task that the agent has to learn can either be to maximize its performance over (i) that fixed period, or (ii) an indefinite period where time limits are only used during training to diversify experience. In this paper, we provide a formal account for how time limits could effectively be handled in each of the two cases and explain why not doing so can cause state-aliasing and invalidation of experience replay, leading to suboptimal policies and training instability. In case (i), we argue that the terminations due to time limits are in fact part of the environment, and thus a notion of the remaining time should be included as part of the agent's input to avoid violation of the Markov property. In case (ii), the time limits are not part of the environment and are only used to facilitate learning. We argue that this insight should be incorporated by bootstrapping from the value of the state at the end of each partial episode. For both cases, we illustrate empirically the significance of our considerations in improving the performance and stability of existing reinforcement learning algorithms, showing state-of-the-art results on several control tasks.
Deciphering Structural Photophysics of Fluorescent Proteins by Kinetic Crystallography

Because they enable labeling of biological samples in a genetically-encoded manner, Fluorescent Proteins (FPs) have revolutionized life sciences. Photo-transformable fluorescent proteins (PTFPs), in particular, recently attracted wide interest, as their fluorescence state can be actively modulated by light, a property central to the emergence of super-resolution microscopy. PTFPs, however, exhibit highly complex photophysical behaviours that are still poorly understood, hampering the rational engineering of variants with improved performances. We show that kinetic crystallography combined with in crystallo optical spectroscopy, modeling approaches and single-molecule measurements constitutes a powerful tool to decipher processes such as photoactivation, photoconversion, photoswitching, photoblinking and photobleaching. Besides potential applications for the design of enhanced PTFPs, these investigations provide fundamental insight into photoactivated protein dynamics.
Improved Calcium Scoring at Dual-Energy Computed Tomography Angiography Using a High-Z Contrast Element and Novel Material Separation Technique

Objectives The aim of this study was to compare the accuracy of existing dual-energy computed tomography (CT) angiography coronary artery calcium scoring methods to those obtained using an experimental tungsten-based contrast material and a recently described contrast material extraction process (CMEP). Methods Phantom coronary arteries of varied diameters, with different densities and arcs of simulated calcified plaque, were sequentially filled with water, iodine, and tungsten contrast materials and scanned within a thorax phantom at rapid-kVp-switching dual-energy CT. Calcium and contrast density images were obtained by material decomposition (MD) and CMEP. Relative calcium scoring errors among the 4 reconstructed datasets were compared with a ground truth, 120-kVp dataset. Results Compared with the 120-kVp dataset, tungsten CMEP showed a significantly lower mean absolute error in calcium score (6.2%, P < 0.001) than iodine CMEP, tungsten MD, and iodine MD (9.9%, 15.7%, and 40.8%, respectively). Conclusions Novel contrast elements and material separation techniques offer improved coronary artery calcium scoring accuracy and show potential to improve the use of dual-energy CT angiography in a clinical setting.
Sensorimotor and Physiological Indicators of Impairment in Mild Traumatic Brain Injury: A Meta-Analysis

Objective. To systematically review the literature with meta-analysis to determine whether persistence of sensorimotor or physiological impairment exists between 4 weeks to 6 months post mild traumatic brain injury (mTBI), and assign level of evidence to findings. Method. The databases PubMed, pscyINFO, SPORTdiscus, Medline, CINAHL and Embase were searched from inception to November 2016 using a priori inclusion criteria. Critical appraisal was performed, and an evidence matrix established level of evidence. Meta-analysis of pooled results identified standardized mean difference (SMD) and 95% confidence intervals (95% CI) between mTBI and healthy controls for a variety of physiological and sensorimotor indicators. Results. Eighteen eligible articles, with a mean quality score of 15.67 (SD = 2.33) were included in the final review. Meta-analysis of center of motion variable; maximal mediolateral center of motion/center of pressure separation distance SMD [95% CI] approached significance at (−0.42 [−0.84, −0.00], I2 = 0%) for dual task, level walking indicating a potential reduction in maximal mediolateral excursion during gait in the mTBI group compared to healthy controls. Significantly reduced variability in the standard deviation of heart beat intervals was observed in the mTBI group (−0.51 [−0.74, −0.28], I2 = 0%). Overall, significant group differences in 36 sensorimotor and physiological variables (eg, balance, gait velocity and motion analysis outcomes, various oculomotor tasks, as well as heart rate variability frequency domains) were identified. Conclusion. Findings demonstrate that persistence of sensorimotor and physiological changes beyond expected recovery times following subacute mTBI in an adult population is possible. These findings have implications for post-injury assessment and management.
Physical Characteristics of Arctic Fox ( Alopex lagupus ) Dens in Svalbard

Physical characteristics of 73 arctic fox (Alopex lagopus) dens in Svalbard are described. In a mountainous study area of 975 km2, most dens were found below 200 m and none was found above 400 m. Most dens were located in slopes in valleys or along the coast, facing in a southerly direction (mean aspect 222’). Dens had an average of 9.8 entrances and a mean size of 52.1 m2. Snow cover was less over dens than on adjacent areas in winter. Vegetation at dens was different than at adjacent areas. Of 56 dens found in the study area, 3 were burrows and the rest were situated under boulders, in screes or in bedrock. Dens were situated in dry localities, most often in protruding bedrock and ridges, where foxes had an unrestricted view.
JAK2 Inhibitor SAR302503 Abrogates PD-L1 Expression and Targets Therapy-Resistant Non–small Cell Lung Cancers

Lung cancer is the leading cause of cancer-related deaths worldwide. Approximately 85% of all lung cancers are non–small cell histology [non–small cell lung cancer (NSCLC)]. Modern treatment strategies for NSCLC target driver oncogenes and immune checkpoints. However, less than 15% of patients survive beyond 5 years. Here, we investigated the effects of SAR302503 (SAR), a selective JAK2 inhibitor, on NSCLC cell lines and tumors. We show that SAR is cytotoxic to NSCLC cells, which exhibit resistance to genotoxic therapies, such as ionizing radiation, cisplatin, and etoposide. We demonstrate that constitutive IFN-stimulated gene expression, including an IFN-related DNA damage resistance signature, predicts for sensitivity to SAR. Importantly, tumor cell–intrinsic expression of PD-L1 is IFN-inducible and abrogated by SAR. Taken together, these findings suggest potential dual roles for JAK2 inhibitors, both as a novel monotherapy in NSCLCs resistant to genotoxic therapies, and in tandem with immune checkpoint inhibition. Mol Cancer Ther; 17(4); 732–9. ©2018 AACR.
Effect of Opioid vs Nonopioid Medications on Pain-Related Function in Patients With Chronic Back Pain or Hip or Knee Osteoarthritis Pain: The SPACE Randomized Clinical Trial

Importance Limited evidence is available regarding long-term outcomes of opioids compared with nonopioid medications for chronic pain. Objective To compare opioid vs nonopioid medications over 12 months on pain-related function, pain intensity, and adverse effects. Design, Setting, and Participants Pragmatic, 12-month, randomized trial with masked outcome assessment. Patients were recruited from Veterans Affairs primary care clinics from June 2013 through December 2015; follow-up was completed December 2016. Eligible patients had moderate to severe chronic back pain or hip or knee osteoarthritis pain despite analgesic use. Of 265 patients enrolled, 25 withdrew prior to randomization and 240 were randomized. Interventions Both interventions (opioid and nonopioid medication therapy) followed a treat-to-target strategy aiming for improved pain and function. Each intervention had its own prescribing strategy that included multiple medication options in 3 steps. In the opioid group, the first step was immediate-release morphine, oxycodone, or hydrocodone/acetaminophen. For the nonopioid group, the first step was acetaminophen (paracetamol) or a nonsteroidal anti-inflammatory drug. Medications were changed, added, or adjusted within the assigned treatment group according to individual patient response. Main Outcomes and Measures The primary outcome was pain-related function (Brief Pain Inventory [BPI] interference scale) over 12 months and the main secondary outcome was pain intensity (BPI severity scale). For both BPI scales (range, 0-10; higher scores = worse function or pain intensity), a 1-point improvement was clinically important. The primary adverse outcome was medication-related symptoms (patient-reported checklist; range, 0-19). Results Among 240 randomized patients (mean age, 58.3 years; women, 32 [13.0%]), 234 (97.5%) completed the trial. Groups did not significantly differ on pain-related function over 12 months (overall P = .58); mean 12-month BPI interference was 3.4 for the opioid group and 3.3 for the nonopioid group (difference, 0.1 [95% CI, −0.5 to 0.7]). Pain intensity was significantly better in the nonopioid group over 12 months (overall P = .03); mean 12-month BPI severity was 4.0 for the opioid group and 3.5 for the nonopioid group (difference, 0.5 [95% CI, 0.0 to 1.0]). Adverse medication-related symptoms were significantly more common in the opioid group over 12 months (overall P = .03); mean medication-related symptoms at 12 months were 1.8 in the opioid group and 0.9 in the nonopioid group (difference, 0.9 [95% CI, 0.3 to 1.5]). Conclusions and Relevance Treatment with opioids was not superior to treatment with nonopioid medications for improving pain-related function over 12 months. Results do not support initiation of opioid therapy for moderate to severe chronic back pain or hip or knee osteoarthritis pain. Trial Registration clinicaltrials.gov Identifier: NCT01583985
Role of Macrophage Socs3 in the Pathogenesis of Aortic Dissection

Background Aortic dissection (AD) is a life‐threatening medical emergency caused by the abrupt destruction of the intimomedial layer of the aortic walls. Given that previous studies have reported the involvement of proinflammatory cytokine interleukin‐6 in AD pathogenesis, we investigated the role of signal transduction and activator of transcription 3 signaling, a downstream pathway of interleukin‐6 in macrophages in pathogenesis of AD. Methods and Results We characterized the pathological and molecular events triggered by aortic stress, which can lead to AD. Aortic stress on the suprarenal aorta because of infrarenal aorta stiffening and angiotensin II infusion for 1 week caused focal medial rupture at the branching point of the celiac trunk and superior mesenteric artery. This focal medial rupture healed in 6 weeks in wild‐type (WT) mice, but progressed to AD in mice with macrophage‐specific deletion of Socs3 gene (mSocs3‐KO). mSocs3‐KO mice showed premature activation of cell proliferation, an inflammatory response, and skewed differentiation of macrophages toward the tissue‐destructive phenotype. Concomitantly, they showed aberrant phenotypic modulation of smooth muscle cells and transforming growth factor beta signaling, which are likely to participate in tissue repair. Human AD samples revealed signal transduction and activator of transcription 3 activation in adventitial macrophages adjacent to the site of tissue destruction. Conclusions These findings suggest that AD development is preceded by focal medial rupture, in which macrophage Socs3 maintains proper inflammatory response and differentiation of SMCs, thus promoting fibrotic healing to prevent tissue destruction and AD development. Understanding the sequence of the pathological and molecular events preceding AD development will help predict and prevent AD development and progression.