Miracle-dz/UniFAR-FTUs huggingface dataset:
Sequential Maturation of Olfactory Sensory Neurons in the Mature Olfactory Epithelium

Abstract The formation of the olfactory nerve and olfactory bulb (OB) glomeruli begins embryonically in mice. However, the development of the olfactory system continues throughout life with the addition of new olfactory sensory neurons (OSNs) in the olfactory epithelium (OE). Much attention has been given to the perinatal innervation of the OB by OSN axons, but in the young adult the process of OSN maturation and axon targeting to the OB remains controversial. To address this gap in understanding, we used BrdU to label late-born OSNs in young adult mice at postnatal day 25 (P25-born OSNs) and timed their molecular maturation following basal cell division. We show that OSNs in young adults undergo a sequential molecular development with the expression of GAP 43 (growth-associated protein 43) > AC3 (adenylyl cyclase 3) > OMP (olfactory marker protein), consecutively, in a time frame of ∼8 d. To assess OSN axon development, we implemented an in vivo fate-mapping strategy to label P25-born OSNs with ZsGreen. Using sampling intervals of 24 h, we demonstrate the progressive extension of OSN axons in the OE, through the foramen of the cribriform plate, and onto the surface of the OB. OSN axons reached the OB and began to target and robustly innervate specific glomeruli ∼10 d following basal cell division, a time point at which OMP expression becomes evident. Our data demonstrate a sequential process of correlated axon extension and molecular maturation that is similar to that seen in the neonate, but on a slightly longer timescale and with regional differences in the OE.
Comparison of the Effects of Ticagrelor and Clopidogrel on Microvascular Dysfunction in Patients With Acute Coronary Syndrome Using Invasive Physiologic Indices.

BACKGROUND Ticagrelor reduced the rate of myocardial infarction and death compared with clopidogrel in patients with acute coronary syndrome. However, little is understood about chronic treatment of ticagrelor on microvascular dysfunction. The objective of this study was to assess the impact of ticagrelor maintenance treatment on microvascular system and coronary flow in comparison with clopidogrel. METHODS This study was a nonblinded, open-label, parallel-group, prospective, randomized controlled trial that enrolled 120 patients with acute coronary syndrome requiring stent implantation. Patients were randomized into the ticagrelor (180 mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300 to 600 mg loading dose, 75 mg daily thereafter) group. The primary end point was coronary microvascular dysfunction as measured by an index of microcirculatory resistance (IMR) at 6 months after treatment. RESULTS The baseline clinical characteristics and physiological parameters, such as fractional flow reserve, coronary flow reserve, and IMR, did not differ between the ticagrelor and clopidogrel groups. Six-month follow-up physiological data showed that the IMR value was significantly lower in the ticagrelor group than the clopidogrel group (15.57±5.65 versus 21.15±8.39, P<0.01), and coronary flow reserve was higher in the ticagrelor group than in the clopidogrel group (3.85±0.72 versus 3.37±0.76, P<0.01). However, there was no difference in fractional flow reserve (0.87±0.08 versus 0.87±0.09, P=0.94) between the 2 groups. The improvement in IMR after 6 months of treatment was higher in the ticagrelor group (P<0.01). Analyses of 223 nonculprit vessels of registered patients based on physiological results showed no differences in baseline fractional flow reserve (0.93±0.13 versus 0.92±0.09, P=0.58), coronary flow reserve (3.62±1.27 versus 3.51±1.24, P=0.16), or IMR (21.37±12.37 versus 24.19±21.08, P=0.22) or in follow-up fractional flow reserve (0.91±0.09 versus 0.91±0.08, P=0.67), coronary flow reserve (3.91±1.22 versus 3.75±1.16, P=0.36), or IMR (19.43±10.32 versus 21.52±18.90, P=0.34) between the 2 groups. CONCLUSIONS Compared with clopidogrel, 6 months of ticagrelor therapy significantly improved microvascular dysfunction in acute coronary syndrome patients with stent implantation. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials. gov. Unique identifier: NCT02618733.
Pre-diagnostic Leukocyte Mitochondrial DNA Copy Number and Colorectal Cancer Risk.

Mitochondrial DNA (mtDNA) is susceptible to oxidative stress and mutation. Few epidemiological studies have assessed the relationship between mtDNA copy number (mtDNAcn) and risk of colorectal cancer (CRC), with inconsistent findings. In this study, we examined the association between pre-diagnostic leukocyte mtDNAcn and CRC risk in a case-control study of 324 female cases and 658 matched controls nested within the Nurses' Health Study (NHS). Relative mtDNAcn in peripheral blood leukocytes was measured by quantitative PCR-based assay. Conditional logistic regression models were applied to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association of interest. Results showed lower log-mtDNAcn was significantly associated with increased risk of CRC, in a dose-dependent relationship (P for trend < 0.0001). Compared to the 4th quartile, multivariable-adjusted OR (95% CI) was 1.10 (0.69, 1.76) for the 3rd quartile, 1.40 (0.89, 2.19) for the 2nd quartile, and 2.19 (1.43, 3.35) for the 1st quartile. In analysis by anatomic subsite of CRC, we found a significant inverse association for proximal colon cancer [lowest vs. highest quartile, multivariable-adjusted OR (95% CI) = 3.31 (1.70, 6.45), P for trend = 0.0003]. Additionally, stratified analysis according to the follow-up time since blood collection showed that the inverse association between mtDNAcn and CRC remained significant among individuals with ≥ 5 years' follow-up, and marginally significant among those with ≥ 10 years' follow-up since mtDNAcn testing, suggesting that mtDNAcn may serve as a long-term predictor for risk of CRC. In conclusion, pre-diagnostic leukocyte mtDNAcn was inversely associated with CRC risk. Further basic experimental studies are needed to explore the underlying biological mechanisms linking mtDNAcn to CRC carcinogenesis.
Targeting Foam Cell Formation in Atherosclerosis: Therapeutic Potential of Natural Products

Foam cell formation and further accumulation in the subendothelial space of the vascular wall is a hallmark of atherosclerotic lesions. Targeting foam cell formation in the atherosclerotic lesions can be a promising approach to treat and prevent atherosclerosis. The formation of foam cells is determined by the balanced effects of three major interrelated biologic processes, including lipid uptake, cholesterol esterification, and cholesterol efflux. Natural products are a promising source for new lead structures. Multiple natural products and pharmaceutical agents can inhibit foam cell formation and thus exhibit antiatherosclerotic capacity by suppressing lipid uptake, cholesterol esterification, and/or promoting cholesterol ester hydrolysis and cholesterol efflux. This review summarizes recent findings on these three biologic processes and natural products with demonstrated potential to target such processes. Discussed also are potential future directions for studying the mechanisms of foam cell formation and the development of foam cell-targeted therapeutic strategies.
Admission Diffusion-Weighted Imaging Lesion Volume in Patients With Large Vessel Occlusion Stroke and Alberta Stroke Program Early CT Score of ≥6 Points: Serial Computed Tomography-Magnetic Resonance Imaging Collateral Measurements.

Background and Purpose- We hypothesized that the pial collateral status at the time of presentation could predict the infarct size on magnetic resonance imaging in patients with similar degrees of early ischemic changes on computed tomography. We tested the association between serial changes in collateral status and infarct volume defined on diffusion-weighted imaging (DWI) in patients with large vessel occlusion and small core. Methods- Consecutive patients who were candidates for endovascular treatment (Alberta Stroke Program Early CT Score [ASPECTS] of ≥6 points) and who underwent both pretreatment multiphasic computed tomography angiography (mCTA) and multimodal magnetic resonance imaging were enrolled. The baseline early ischemic changes and collateral status were determined using both mCTA and magnetic resonance imaging-based collateral maps. Multivariable linear regression was used to evaluate adjusted estimates of the effect of collateral status on predicting MR DWI lesion volume before endovascular treatment. Results- Of 65 patients (39 men; median age, 76 years; median ASPECTS, 8 points [range, 6-10]), 10 (15.4%), 8 (12.3%), and 47 (72.3%) presented poor, intermediate, and good collaterals on mCTA, respectively. After adjusting for the initial stroke severity, ASPECTS, time to DWI, and mismatch volume, the mCTA collateral grade was the only factor independently associated with the DWI lesion volume (β=-35.657, SE mean=3.539; P<0.0001). An excellent correlation between the mCTA- and magnetic resonance imaging-based collateral grades was observed (matching grade seen in 92.3%), suggesting a collateral status persistence during the hyperacute stroke phase. Conclusions- The mCTA assessed collateral adequacy is the sole predictor of eventual DWI lesion volume before endovascular treatment. The added value of collateral assessment in early ischemic changes and large vessel occlusion for decision-making regarding more aggressive revascularizations requires further evaluation. Clinical Trial Registration- URL: https://www.clinicaltrials. gov. Unique identifier: NCT03234634 and NCT02668627.
Microwave-Assisted Synthesis of SPION-Reduced Graphene Oxide Hybrids for Magnetic Resonance Imaging (MRI)

Magnetic resonance imaging (MRI) is a useful tool for disease diagnosis and treatment monitoring. Superparamagnetic iron oxide nanoparticles (SPION) show good performance as transverse relaxation (T2) contrast agents, thus facilitating the interpretation of the acquired images. Attachment of SPION onto nanocarriers prevents their agglomeration, improving the circulation time and efficiency. Graphene derivatives, such as graphene oxide (GO) and reduced graphene oxide (RGO), are appealing nanocarriers since they have both high surface area and functional moieties that make them ideal substrates for the attachment of nanoparticles. We have employed a fast, simple and environmentally friendly microwave-assisted approach for the synthesis of SPION-RGO hybrids. Different iron precursor/GO ratios were used leading to SPION, with a median diameter of 7.1 nm, homogeneously distributed along the RGO surface. Good relaxivity (r2*) values were obtained in MRI studies and no significant toxicity was detected within in vitro tests following GL261 glioma and J774 macrophage-like cells for 24 h with SPION-RGO, demonstrating the applicability of the hybrids as T2-weighted MRI contrast agents.
Concurrent and lagged associations of prescription opioid use with pain and negative affect in the daily lives of chronic pain patients.

OBJECTIVE Prescribed opioids for chronic pain management contribute significantly to the opioid crisis. There is a need to understand the real-world benefits that, despite risks, lead chronic pain patients to persist in opioid use. Negative reinforcement models of addiction posit that individuals use substances to reduce aversive states but have seldom been applied to prescribed opioids. Using ecological momentary assessment, we examined reciprocal associations between opioid use and physical pain, for which opioids are prescribed, and negative affect (NA), for which they are not. METHOD Chronic low back pain patients on long-term opioid therapy (n = 34) without significant past-year opioid misuse reported multiple times daily via smartphone over 2 weeks (nobservations = 2,285). We hypothesized that pain and NA would be positively associated with subsequent opioid use, and that use would be negatively associated with subsequent pain and NA. RESULTS Time-lagged multilevel models indicated that participants were more likely to use opioids and in larger doses following elevated pain and NA. There was also an interaction of concurrent pain and NA on opioid dose. In turn, participants reported reduced pain and NA following larger doses. Additionally, individuals at high risk for opioid misuse, compared with low risk, took larger doses following pain, but also experienced smaller subsequent pain and NA reductions. CONCLUSIONS Opioid use was bidirectionally associated with pain and NA. Findings fit negative reinforcement models associated with risk of developing opioid use disorder. Educating patients and providers about negative reinforcement may help reduce opioid use and opioid-associated risks. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Absolute Free Energy of Binding Calculations for Macrophage Migration Inhibitory Factor in Complex with a Drug-like Inhibitor.

Calculation of the absolute free energy of binding (ΔGbind) for a complex in solution is challenging owing to the need for adequate configurational sampling and an accurate energetic description, typically with a force field (FF). In this study, Monte Carlo (MC) simulations with improved side-chain and backbone sampling are used to assess ΔGbind for the complex of a drug-like inhibitor (MIF180) with the protein macrophage migration inhibitory factor (MIF) using free energy perturbation (FEP) calculations. For comparison, molecular dynamics (MD) simulations were employed as an alternative sampling method for the same system. With the OPLS-AA/M FF and CM5 atomic charges for the inhibitor, the ΔGbind results from the MC/FEP and MD/FEP simulations, 8.80 ± 0.74 and -8.46 ± 0.85 kcal/mol, agree well with each other and with the experimental value of -8.98 ± 0.28 kcal/mol. The convergence of the results and analysis of the trajectories indicate that sufficient sampling was achieved for both approaches. Repeating the MD/FEP calculations using current versions of the CHARMM and AMBER FFs led to a 6-kcal/mol range of computed ΔGbind. These results show that calculation of accurate ΔGbind for large ligands is both feasible and numerically equivalent, within error limits, using either methodology.
Hemispheric tumor location and the impact on health-related quality of life, symptomatology, and functional performance outcomes in patients with glioma: an exploratory cross-sectional study

Abstract Purpose To inform high-quality rehabilitation services, this study investigates if patients with glioma located in the right- or left-hemisphere present with different health-related quality of life, symptomatology, and functional performance in the early disease state. Material and methods Between 2013 and 2017, 81 adult patients were assessed during the first week of chemo-radiation, following resection. Patients were stratified into two groups depending on a right- or left-hemispheric lesion. Independent t-tests analyzed potential differences regarding health-related quality of life, symptomatology, and functional performance. Results Forty-five patients (56%) had a tumor located in the right hemisphere, whereas 36 patients (44%) had a tumor in the left hemisphere. Except for more patients with tumors in the left hemisphere having their tumor located in eloquent brain areas, the groups were well matched. No group differences were found in health-related quality of life. Group differences were found in communication deficits (Δ-10.9, 95%CI −19.1; −2.3, p = 0.01), which were more frequent in patients with left-sided lesions, and of headaches (Δ13.9, 95%CI 1.8; 25.9, p = 0.02), which were more frequent in patients with right-hemispheric lesions, who also had significantly greater difficulties with process-skills when performing everyday life tasks (Δ-0.3, 95%CI −0.5; −0.1, p < 0.01). Also, weak evidence suggests that patients with Glioblastoma Multiforme located in the right hemisphere are more affected by fatigue compared to their left-hemispheric comparisons (Δ14.6, 95%CI 0.19; 29.0, p < 0.05). Conclusions The hemispheric location of a glial-cell brain tumor has no consequence for health-related quality of life at the beginning of chemo-radiation treatments. However, findings of tumor-location dependent conditions of communication, headache, patients’ ability to perform executive functions, and fatigue should be considered in rehabilitation situations when designing an intervention to potentially improve executive functions and relieve the symptoms. Implications for rehabilitation It is unclear if laterality impact glioma patients health-related quality of life and functional performance, which might implicate differentiated rehabilitation interventions. The hemispheric location of a glial-cell brain tumor has no consequence for the health-related quality of life at the beginning of chemo-radiation, following surgery. Tumor-location dependent conditions of communication, headache, fatigue, and patients’ ability to perform executive functions should be considered when designing an intervention to improve executive functions and symptom-relieve. In rehabilitation interventions, tumor laterality is not a factor that needs to be considered before recommending aerobic training to improve the functional capacity of patients with glioma.
Paradigms in business process management specifications: a critical overview

Purpose Despite its popularity, business process management (BPM) is not unequivocally defined, but obtains different forms with varying specifications. This paper presents a critical overview of BPM, as it appears within four dominant management paradigms: total quality management, standardized management systems, business process reengineering and Six Sigma. The purpose of this paper is to explore BPM specifications and compare the BPM implementation potential under each paradigm. Design/methodology/approach This is based on the analysis of a large number of highly cited scholarly publications. In order to identify the nature of BPM within each paradigm, a common framework for comparison is first established and then, for each paradigm, BPM is analyzed according to the main parameters of this framework. Findings Many differences among various BPM forms are paradigm driven. So, the approach adopted by each paradigm (i.e. individual-process or systemic approach) affects the scope and role of BPM. The principles of each paradigm directly affect the attributes assigned to BPM. Despite of important differences, the structure of BPM within all paradigms conforms to the stages of the classical BPM lifecycle. However, each paradigm assigns different weights to each stage and also displays different levels of BPM implementability. Originality/value The paper presents a first systematic comparison of BPM specifications for the dominant management paradigms primarily deployed. It thus explains why many attributes originating from the paradigms have crept into the general BPM specifications. This work can be considered as a step toward defining the core attributes of a paradigm-independent BPM model, thus enhancing its application scope as an invaluable management tool.
Conflicting influences of justice motivations on moral judgments

ABSTRACT Humans are motivated by justice concerns, yet vary in their reactions to observing or experiencing injustice. At a proximate level, approach and avoidance represent core fundamental motivational systems which have been proposed to be involved in two independent moral systems: a prescriptive system responsive to obligations (“shoulds”) and a proscriptive system concerned with prohibitions (“should nots”). It is unclear whether these motivational systems or personal involvement better explain the influence of justice dispositions on moral judgments. To clarify this theoretical argument, two experiments examined how dispositional self-oriented and other-oriented justice sensitivity influence condemnation of prescriptive and proscriptive violations while manipulating perspective between-subject or within-subject. Participants rated the permissibility of everyday moral transgressions, from the perspective of the victim or a neutral observer. In Study 1 (n = 235), self-oriented dispositions increased and other-oriented dispositions decreased the probability of rating prescriptive violations as permissible. Study 2 (n = 468) replicated the effect of other-oriented justice sensitivity. Overall, these results bridge the gap between motivational systems and self-other processing. They suggest that justice sensitivity is better conceptualised as distinct motivations which can exert opposing influences on moral decision-making. Moreover, personal involvement may not be as important as individual justice motivations for explaining everyday moral decision-making.
Organic Soils Control Beetle Survival While Competitors Limit Aphid Population Growth

Abstract Soil chemistry and microbial diversity can impact the vigor and nutritive qualities of plants, as well as plants' ability to deploy anti-herbivore defenses. Soil qualities often vary dramatically on organic versus conventional farms, reflecting the many differences in soil management practices between these farming systems. We examined soil-mediated effects on herbivore performance by growing potato plants (Solanum tuberosum L.) in soils collected from organic or conventional commercial farm fields, and then exposing these plants to herbivory by green peach aphids (Myzus persicae Sulzer, Hemiptera: Aphididae) and/or Colorado potato beetles (Leptinotarsa decemlineata Say, Coleoptera: Chrysomelidae). Responses of the two potato pests varied dramatically. Survivorship of Colorado potato beetles was almost 3× higher on plants grown in organic than in conventional soils, but was unaffected by the presence of aphids. In contrast, aphid colony growth was twice as rapid when aphids were reared alone rather than with Colorado potato beetles, but was unaffected by soil type. We saw no obvious differences in soil nutrients when comparing organic and conventional soils. However, we saw a higher diversity of bacteria in organic soils, and potato plants grown in this soil had a lower carbon concentration in foliar tissue. In summary, the herbivore species differed in their susceptibility to soil- versus competitor-mediated effects, and these differences may be driven by microbe-mediated changes in host plant quality. Our results suggest that soil-mediated effects on pest growth can depend on herbivore species and community composition, and that soil management strategies that promote plant health may also increase host quality for pests.