Miracle-dz/UniFAR-FTUs huggingface dataset:
Genome-Wide Association Studies Based on Equine Joint Angle Measurements Reveal New QTL Affecting the Conformation of Horses

The evaluation of conformation traits is an important part of selection for breeding stallions and mares. Some of these judged conformation traits involve joint angles that are associated with performance, health, and longevity. To improve our understanding of the genetic background of joint angles in horses, we have objectively measured the angles of the poll, elbow, carpal, fetlock (front and hind), hip, stifle, and hock joints based on one photograph of each of the 300 Franches-Montagnes (FM) and 224 Lipizzan (LIP) horses. After quality control, genome-wide association studies (GWASs) for these traits were performed on 495 horses, using 374,070 genome-wide single nucleotide polymorphisms (SNPs) in a mixed-effect model. We identified two significant quantitative trait loci (QTL) for the poll angle on ECA28 (p = 1.36 × 10−7), 50 kb downstream of the ALX1 gene, involved in cranial morphology, and for the elbow joint on ECA29 (p = 1.69 × 10−7), 49 kb downstream of the RSU1 gene, and 75 kb upstream of the PTER gene. Both genes are associated with bone mineral density in humans. Furthermore, we identified other suggestive QTL associated with the stifle joint on ECA8 (p = 3.10 × 10−7); the poll on ECA1 (p = 6.83 × 10−7); the fetlock joint of the hind limb on ECA27 (p = 5.42 × 10−7); and the carpal joint angle on ECA3 (p = 6.24 × 10−7), ECA4 (p = 6.07 × 10−7), and ECA7 (p = 8.83 × 10−7). The application of angular measurements in genetic studies may increase our understanding of the underlying genetic effects of important traits in equine breeding.
Peroxynitrite-Mediated SIRT (Sirtuin)-1 Inactivation Contributes to Nicotine-Induced Arterial Stiffness in Mice.

Objective- Inhibition of SIRT (sirtuin)-1, a nicotinamide adenine dinucleotide-dependent protein deacetylase, is linked to cigarette smoking-induced arterial stiffness, but the underlying mechanisms remain largely unknown. The aim of the present study was to determine the effects and mechanisms of nicotine, a major component of cigarette smoke, on SIRT1 activity and arterial stiffness. Approach and Results- Arterial stiffness, peroxynitrite (ONOO-) formation, SIRT1 expression and activity were monitored in mouse aortas of 8-week-old C57BL/6 mice (wild-type) or Sirt1-overexpressing ( Sirt1 Super) mice with or without nicotine for 4 weeks. In aortas of wild-type mice, nicotine reduced SIRT1 protein and activity by ≈50% without affecting its mRNA levels. In those from Sirt1 Super mice, nicotine also markedly reduced SIRT1 protein and activity to the levels that were comparable to those in wild-type mice. Nicotine infusion significantly induced collagen I, fibronectin, and arterial stiffness in wild-type but not Sirt1 Super mice. Nicotine increased the levels of iNOS (inducible nitric oxide synthase) and the co-staining of SIRT1 and 3-nitrotyrosine, a footprint of ONOO- in aortas. Tempol, which ablated ONOO- by scavenging superoxide anion, reduced the effects of nicotine on SIRT1 and collagen. Mutation of zinc-binding cysteine 395 or 398 in SIRT1 into serine (C395S) or (C398S) abolished SIRT1 activity. Furthermore, ONOO- dose-dependently inhibited the enzyme and increased zinc release in recombinant SIRT1. Finally, we found SIRT1 inactivation by ONOO- activated the YAP (Yes-associated protein) resulting in abnormal ECM (extracellular matrix) remodeling. Conclusions- Nicotine induces ONOO-, which selectively inhibits SIRT1 resulting in a YAP-mediated ECM remodeling.
Detailed Analysis of the Characteristics of Sample Volume in Blood Culture Bottles

Blood volume is the most important variable for the detection of microorganisms in blood cultures (BCs). Most standards recommend 40 to 60 ml blood, collected in several BC bottles filled up to 10 ml. We measured blood volume in individual BC bottles and analyzed the associations of hospital, bottle type, day of the week, daily sampling time, and age and sex of the patient with sampling volume and BC result. ABSTRACT Blood volume is the most important variable for the detection of microorganisms in blood cultures (BCs). Most standards recommend 40 to 60 ml blood, collected in several BC bottles filled up to 10 ml. We measured blood volume in individual BC bottles and analyzed the associations of hospital, bottle type, day of the week, daily sampling time, and age and sex of the patient with sampling volume and BC result. The variation in blood volume per BC bottle was analyzed in a mixed linear model using hospital, bottle type, weekday, sampling time, age, and sex as fixed factors and patient identification (ID) and episode as random factors to control for repetitive sampling of individual patients. Only 18% of all bottles were filled with the recommended 8 to 10 ml, and 47% were filled with less than 8 ml. The mean (± standard error) volume was larger in positive bottles (9.09 ± 0.15) than in negative bottles (8.47 ± 0.07) (P < 0.001). Blood volume was larger in BacT/Alert-FA Plus bottles than in -FN Plus BC bottles (P < 0.001). There were significantly lower volumes collected during the night (P < 0.001). The volume of blood collected decreased significantly with increasing patient age (P < 0.001). Larger volumes were collected from male patients than from female patients: 8.78 (± 0.06) versus 8.36 (± 0.06) ml (mean ± standard error [SE]), respectively (P < 0.001). The odds of detecting a positive patient increases by 13% for each additional milliliter of blood drawn. Our results show that we need to work actively with the development of blood sampling routines to overcome age and sex effects and to optimize blood sampling volumes.
Polyphosphate kinase is involved in stress‐induced mprAB‐sigE‐rel signalling in mycobacteria

Polyphosphate kinase 1 (PPK1) helps bacteria to survive under stress. The ppk1 gene of Mycobacterium tuberculosis was overexpressed in Escherichia coli and characterized. Residues R230 and F176, predicted to be present in the head domain of PPK1, were identified as residues critical for polyphosphate (polyP)‐synthesizing ability and dimerization of PPK1. A ppk1 knockout mutant of Mycobacterium smegmatis was compromised in its ability to survive under long‐term hypoxia. The transcription of the rel gene and the synthesis of the stringent response regulator ppGpp were impaired in the mutant and restored after complementation with ppk1 of M. tuberculosis, providing evidence that PPK1 is required for the stringent response. We present evidence that PPK1 is likely required for mprAB‐sigE‐rel signalling. σE regulates the transcription of rel, and we hypothesize that under conditions of stress polyP acts as a preferred donor for MprB‐mediated phosphorylation of MprA facilitating transcription of the sigE gene thereby leading finally to the enhancement of the transcription of rel in M. smegmatis and M. tuberculosis. Downregulation of ppk1 led to impaired survival of M. tuberculosis in macrophages. PolyP plays a central role in the stress response of mycobacteria.
Sex Differences Persist in Time to Presentation, Revascularization, and Mortality in Myocardial Infarction Treated With Percutaneous Coronary Intervention

Background Timely revascularization with percutaneous coronary intervention (PCI) reduces death following myocardial infarction. We evaluated if a sex gap in symptom‐to‐door (STD), door‐to‐balloon (DTB), and door‐to‐PCI time persists in contemporary patients, and its impact on mortality. Methods and Results From 2013 to 2016 the Victorian Cardiac Outcomes Registry prospectively recruited 13 451 patients (22.5% female) from 30 centers with ST‐segment–elevation myocardial infarction (STEMI, 47.8%) or non–ST‐segment–elevation myocardial infarction (NSTEMI) (52.2%) who underwent PCI. Adjusted log‐transformed STD and DTB time in the STEMI cohort and STD and door‐to‐PCI time in the NSTEMI cohort were analyzed using linear regression. Logistic regression was used to determine independent predictors of 30‐day mortality. In STEMI patients, women had longer log‐STD time (adjusted geometric mean ratio 1.20, 95% CI 1.12‐1.28, P<0.001), log‐DTB time (adjusted geometric mean ratio 1.12, 95% CI 1.05‐1.20, P=0.001), and 30‐day mortality (9.3% versus 6.5%, P=0.005) than men. Womens’ adjusted geometric mean STD and DTB times were 28.8 and 7.7 minutes longer, respectively, than were mens’ times. Women with NSTEMI had no difference in adjusted STD, door‐to‐PCI time, or early (<24 hours) versus late revascularization, compared with men. Female sex independently predicted a higher 30‐day mortality (odds ratio 1.67, 95% CI 1.11‐2.49, P=0.01) in STEMI but not in NSTEMI. Conclusions Women with STEMI have significant delays in presentation and revascularization with a higher 30‐day mortality compared with men. The delay in STD time was 4‐fold the delay in DTB time. Women with NSTEMI had no delay in presentation or revascularization, with mortality comparable to men. Public awareness campaigns are needed to address women's recognition and early action for STEMI.
Heart and mind: behavioural cardiology demystified for the clinician

### Learning objectives Dr Stratin is sitting in a clinic with Mr B, a 45-year-old man who had an anterior ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention 6 weeks ago. He felt ‘fixed’ by his treatment and was shocked but relieved to be discharged home after 3 days. He lives alone and has returned to his work as a self-employed builder. Mr B has continued to smoke after his acute myocardial infarction. He is also anxious about his risk of future recurrence and has had to question his assumptions about his physical health and expectations about his health in future years. He is obese and not undertaking any structured exercise. His blood pressure is elevated and he admits that the way in which he takes his cardioprotective medication is a ‘bit hit and miss’. This clinical scenario illustrates common psychosocial factors that can impact negatively on a patient’s recovery and clinical outcomes following treatment for STEMI. These factors will be described and strategies that can be applied to Mr B’ care summarised. Behavioural cardiology is defined as ‘the study and application of psychosocial factors in the assessment and reduction of cardiovascular risk’. 1 Over the last 15 years, there has been a growing recognition that psychosocial risk factors make a significant contribution to the atherosclerotic process leading to cardiovascular disease (CVD) through biological and behavioural mechanisms.2 It is recognised that psychosocial risk factors, such as depression and social isolation, are as potent as many biological and behavioural coronary risk factors. In this paper, we will …
The ITIM Domain–Containing NK Receptor Ly49Q Impacts Pulmonary Infection by Mediating Neutrophil Functions

Pulmonary infection is a frequent pathology associated with excessive neutrophil infiltration. Ly49Q, an ITIM domain–bearing receptor expressed on different leukocytes, has been recently reported to impact neutrophil migration and polarization. Utilizing a murine model of Klebsiella pneumoniae–induced pulmonary infection in combination with additional in vivo and in vitro assays, we show that Ly49Q is critically involved in different steps of the leukocyte adhesion cascade. Ly49Q deficiency is associated with a reduced rolling velocity, impaired crawling capacity, and diminished transmigration. We show that overactivation of the neutrophil β2 integrins Mac-1 and LFA-1 is responsible for increased adhesion and reduced neutrophil transmigration, resulting in a strongly impaired immune defense against pulmonary infection. Structure function analysis in vitro and in vivo demonstrated that different domains of Ly49Q are important for its function. In summary, Ly49Q regulates integrin activation and neutrophil recruitment and is required for an adequate immune response in pulmonary infection.
Human sebum requires de novo lipogenesis, which is increased in acne vulgaris and suppressed by acetyl-CoA carboxylase inhibition

De novo lipogenesis is essential for human sebum production, and increased lipogenic flux accounts for excessive sebum production in acne vulgaris. Getting the skinny on sebum Sebum, an oily material secreted by glands in the skin, has a physiological role, but abnormally high secretion of sebum can be associated with acne. Through a detailed investigation of sebum production in human skin samples and volunteer individuals, Esler et al. determined that most of the sebum in human skin is generated through de novo lipogenesis rather than recycled from circulating lipids. With this knowledge, the authors designed an inhibitor of acetyl-CoA carboxylase, a key enzyme in de novo lipogenesis, and tested it in cells, in rats, and in humans. This compound was well tolerated and successfully suppressed sebum production in human individuals. Sebum plays important physiological roles in human skin. Excess sebum production contributes to the pathogenesis of acne vulgaris, and suppression of sebum production reduces acne incidence and severity. We demonstrate that sebum production in humans depends on local flux through the de novo lipogenesis (DNL) pathway within the sebocyte. About 80 to 85% of sebum palmitate (16:0) and sapienate (16:1n10) were derived from DNL, based on stable isotope labeling, much higher than the contribution of DNL to triglyceride palmitate in circulation (~20%), indicating a minor contribution by nonskin sources to sebum lipids. This dependence on local sebocyte DNL was not recapitulated in two widely used animal models of sebum production, Syrian hamsters and Göttingen minipigs. Confirming the importance of DNL for human sebum production, an acetyl-CoA carboxylase inhibitor, ACCi-1, dose-dependently suppressed DNL and blocked synthesis of fatty acids, triglycerides, and wax esters but not free sterols in human sebocytes in vitro. ACCi-1 dose-dependently suppressed facial sebum excretion by ~50% (placebo adjusted) in human individuals dosed orally for 2 weeks. Sebum triglycerides, wax esters, and free fatty acids were suppressed by ~66%, whereas non–DNL-dependent lipid species, cholesterol, and squalene were not reduced, confirming selective modulation of DNL-dependent lipids. Last, individuals with acne vulgaris exhibited increased sebum production rates relative to individuals with normal skin, with >80% of palmitate and sapienate derived from DNL. These findings highlight the importance of local sebocyte DNL for human skin sebaceous gland biology and illuminate a potentially exploitable therapeutic target for the treatment of acne vulgaris.
Found Graph Data and Planted Vertex Covers

A typical way in which network data is recorded is to measure all the interactions among a specified set of core nodes; this produces a graph containing this core together with a potentially larger set of fringe nodes that have links to the core. Interactions between pairs of nodes in the fringe, however, are not recorded by this process, and hence not present in the resulting graph data. For example, a phone service provider may only have records of calls in which at least one of the participants is a customer; this can include calls between a customer and a non-customer, but not between pairs of non-customers. Knowledge of which nodes belong to the core is an important piece of metadata that is crucial for interpreting the network dataset. But in many cases, this metadata is not available, either because it has been lost due to difficulties in data provenance, or because the network consists of found data obtained in settings such as counter-surveillance. This leads to a natural algorithmic problem, namely the recovery of the core set. Since the core set forms a vertex cover of the graph, we essentially have a planted vertex cover problem, but with an arbitrary underlying graph. We develop a theoretical framework for analyzing this planted vertex cover problem, based on results in the theory of fixed-parameter tractability, together with algorithms for recovering the core. Our algorithms are fast, simple to implement, and out-perform several methods based on network core-periphery structure on various real-world datasets.
Enhanced Hidden Moving Target Defense in Smart Grids

Recent research has proposed a moving target defense (MTD) approach that actively changes transmission line susceptance to preclude stealthy false data injection (FDI) attacks against the state estimation of a smart grid. However, existing studies were often conducted under a weak adversarial setting, in that they ignore the possibility that alert attackers can also try to detect the activation of MTD before they launch the FDI attacks. We call this new threat as parameter confirming-first (PCF) FDI. To improve the stealthiness of MTD, we propose a hidden MTD approach that cannot be detected by the attackers and prove its equivalence to an MTD that maintains the power flows of the whole grid. Moreover, we analyze the completeness of MTD and show that any hidden MTD is incomplete in that FDI attacks may bypass the hidden MTD opportunistically. This result suggests that the stealthiness and completeness are two conflicting goals in MTD design. Finally, we propose an approach to enhancing the hidden MTD against a class of highly structured FDI attacks. We also discuss the MTD’s operational costs under the dc and ac models. We conduct simulations to show the effectiveness of the hidden MTD against PCF-FDI attacks under realistic settings.
A diffusion-model analysis of timing deficits among children with ADHD.

OBJECTIVE Deficits in the ability to perceive time have been proposed as an etiologic mechanism in the development of the cognitive and behavioral characteristics associated with ADHD. However, previous studies testing the presence of timing deficits have produced idiosyncratic results. This is in large part due to the underutilization of insights from basic timing research, and from the inherent difficulty that arises when a single index of performance (i.e., reaction time [RT] or accuracy) is used to index the health of what is essentially a multiple-component process. The current article utilizes a diffusion model approach to isolate the component processes involved in timing (i.e., internal clock speed, decision-making speed, speed/accuracy trade-off strategies, and nondecision time) using a well-validated timing task. METHOD Fifty children with ADHD and 32 non-ADHD controls aged 8-12 completed a temporal bisection procedure. RESULTS Diffusion model parameters indicated that both the internal clock and decision-making speeds were slower among children with ADHD. However, the strength of evidence for slowed decision making far outweighed evidence for a slower internal clock. CONCLUSIONS Slower evidence accumulation during decision making is domain-general deficit in ADHD. Such slowing is consistent with adaptive-gain theories, which posit that a suboptimal ratio of neural signal-to-noise is characteristic of children with ADHD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Effect of Benzothiadiazole on the Metabolome of Tomato Plants Infected by Citrus Exocortis Viroid

Benzothiadiazole (BTH) is a functional analogue of the phytohormone salycilic acid (SA) involved in the plant immune response. NahG tomato plants are unable to accumulate SA, which makes them hypersusceptible to several pathogens. Treatments with BTH increase the resistance to bacterial, fungal, viroid, or viral infections. In this study, metabolic alterations in BTH-treated Money Maker and NahG tomato plants infected by citrus exocortis viroid (CEVd) were investigated by nuclear magnetic resonance spectroscopy. Using multivariate data analysis, we have identified defence metabolites induced after viroid infection and BTH-treatment. Glycosylated phenolic compounds include gentisic and ferulic acid accumulated in CEVd-infected tomato plants, as well as phenylalanine, tyrosine, aspartate, glutamate, and asparagine. Besides, an increase of γ-aminobutyric acid (GABA), glutamine, adenosine, and trigonelline, contributed to a clear discrimination between the metabolome of BTH-treated tomato leaves and their corresponding controls. Among them, GABA was the only metabolite significantly accumulated in both genotypes after the chemical treatment. In view of these results, the addition of GABA was performed on tomato plants infected by CEVd, and a reversion of the NahG hypersusceptibility to CEVd was observed, indicating that GABA could regulate the resistance to CEVd induced by BTH.
Distribution channel under competing supply chain

We examine supply chain distribution channels for two manufacturers selling substitutable products to retailers. Both retailers are Stackelberg leaders and the manufacturers are followers. retailers in competing supply chain may choose different distribution channels, either a traditional distribution or offering a retailing platform. Under supply chain competition, we identify which chanel is more advantageous for each supply chain, and under what circumstances.
Acute ischemic myelopathy treated with intravenous thrombolysis: Four new cases and literature review

Background Intravenous thrombolysis is a well-established treatment of ischemic stroke within 4.5 h. However, its effectiveness in acute ischemic myelopathy is unknown. Purpose We describe a series of four acute ischemic myelopathy patients treated with intravenous thrombolysis within 4.5 h and review the current literature to explore this treatment feasibility, potential safety, and efficacy. Methods We reviewed all routinely collected clinical, radiological, and follow-up data of patients with a final acute ischemic myelopathy diagnosis who received acute intravenous thrombolysis in our stroke network. We also reviewed thrombolyzed acute ischemic myelopathy patients in the literature. Results Four patients (three women) aged 57 to 83 years presented with acute uni- or bilateral extremity paresis, considered initially as cerebral strokes in two of them. After excluding contraindications by brain imaging in three, spinal computed tomography in one and confirmation of acute ischemic myelopathy on spinal magnetic resonance imaging in one patient, intravenous thrombolysis was administered at 135, 190, 240, and 245 min accordingly. Subacute diffusion-weighted imaging-magnetic resonance imaging confirmed acute ischemic myelopathy in all but one patient. Favorable outcome was achieved in two patients rapidly and in three patients at three-month follow-up. We identified seven other thrombolyzed acute ischemic myelopathy patients in the literature, who showed variable recovery and no hemorrhagic complications. Conclusions With appropriate acute imaging, intravenous thrombolysis after acute ischemic myelopathy is feasible and potentially safe within 4.5 h. Given the potential of benefit of thrombolysis in acute ischemic myelopathy, this treatment warrants further efficacy and safety studies.