Miracle-dz/UniFAR-FTUs huggingface dataset:
LXR Alpha Restricts Gammaherpesvirus Reactivation from Latently Infected Peritoneal Cells

Liver X receptors (LXRs) are nuclear receptors that mediate cholesterol and fatty acid homeostasis. Importantly, as ligand-activated transcription factors, LXRs represent potential targets for the treatment of hypercholesterolemia and atherosclerosis. Here, we demonstrate that LXRα, one of the two LXR isoforms, restricts reactivation of latent gammaherpesvirus from peritoneal cells. As gammaherpesviruses are ubiquitous oncogenic agents, LXRs may represent a targetable host factor for the treatment of poorly controlled gammaherpesvirus infection and associated lymphomagenesis. ABSTRACT Gammaherpesviruses are ubiquitous viruses that establish lifelong infections. Importantly, these viruses are associated with numerous cancers and lymphoproliferative diseases. While risk factors for developing gammaherpesvirus-driven cancers are poorly understood, it is clear that elevated viral reactivation from latency often precedes oncogenesis. Here, we demonstrate that the liver X receptor alpha isoform (LXRα) restricts gammaherpesvirus reactivation in an anatomic-site-specific manner. We have previously demonstrated that deficiency of both LXR isoforms (α and β) leads to an increase in fatty acid and cholesterol synthesis in primary macrophage cultures, with a corresponding increase in gammaherpesvirus replication. Interestingly, expression of fatty acid synthesis genes was not derepressed in LXRα-deficient hosts, indicating that the antiviral effects of LXRα are independent of lipogenesis. Additionally, the critical host defenses against gammaherpesvirus reactivation, virus-specific CD8+ T cells and interferon (IFN) signaling, remained intact in the absence of LXRα. Remarkably, using a murine gammaherpesvirus 68 (MHV68) reporter virus, we discovered that LXRα expression dictates the cellular tropism of MHV68 in the peritoneal cavity. Specifically, LXRα−/− mice exhibit reduced latency within the peritoneal B cell compartment and elevated latency within F4/80+ cells. Thus, LXRα restricts gammaherpesvirus reactivation through a novel mechanism that is independent of the known CD8+ T cell-based antiviral responses or changes in lipid synthesis and likely involves changes in the tropism of MHV68 in the peritoneal cavity. IMPORTANCE Liver X receptors (LXRs) are nuclear receptors that mediate cholesterol and fatty acid homeostasis. Importantly, as ligand-activated transcription factors, LXRs represent potential targets for the treatment of hypercholesterolemia and atherosclerosis. Here, we demonstrate that LXRα, one of the two LXR isoforms, restricts reactivation of latent gammaherpesvirus from peritoneal cells. As gammaherpesviruses are ubiquitous oncogenic agents, LXRs may represent a targetable host factor for the treatment of poorly controlled gammaherpesvirus infection and associated lymphomagenesis.
Wnt produced by stretched roof-plate cells is required for the promotion of cell proliferation around the central canal of the spinal cord

ABSTRACT Cell morphology changes dynamically during embryogenesis, and these changes create new interactions with surrounding cells, some of which are presumably mediated by intercellular signaling. However, the effects of morphological changes on intercellular signaling remain to be fully elucidated. In this study, we examined the effect of morphological changes in Wnt-producing cells on intercellular signaling in the spinal cord. After mid-gestation, roof-plate cells stretched along the dorsoventral axis in the mouse spinal cord, resulting in new contact at their tips with the ependymal cells that surround the central canal. Wnt1 and Wnt3a were produced by the stretched roof-plate cells and delivered to the cell process tip. Whereas Wnt signaling was activated in developing ependymal cells, Wnt activation in dorsal ependymal cells, which were close to the stretched roof plate, was significantly suppressed in embryos with roof plate-specific conditional knockout of Wls, which encodes a factor that is essential for Wnt secretion. Furthermore, proliferation of these cells was impaired in Wls conditional knockout mice during development and after induced spinal cord injury in adults. Therefore, morphological changes in Wnt-producing cells appear to generate new Wnt signal targets. Summary: Roof-plate cells stretch along the dorsoventral axis of the developing spinal cord and provide a source of Wnt ligands for the proliferation of dorsal ependymal cells.
Higher education teachers' experiences with learning analytics in relation to student retention

This paper presents findings from a study of Australian and New Zealand academics (n = 276) that teach tertiary education students. The study aimed to explore participants’ early experiences of learning analytics in a higher education milieu in which data analytics is gaining increasing prominence. Broadly speaking participants were asked about: (1) Their teaching context, (2) Their current student retention activities, (3) Their involvement in, and aspirations for, learning analytics use, (4) Their relationship with their institution around learning analytics. The sampled teaching staff broadly indicated a high level of interest but limited level of substantive involvement in learning analytics projects and capacity building activities. Overall, the intention is to present a critical set of voices that assist in identifying and understanding key issues and draw connections to the broader work being done in the field.
Prevalence and risk factors for restless legs syndrome during pregnancy in a Northern Italian population

Abstract The objective of the present study was to investigate the frequency and the risk factors for restless legs syndrome (RLS) during pregnancy in an Italian population rarely studied, in epidemiological studies on the syndrome. A total of 648 women (median age: 35 years; interquartile range: 32–38), who delivered on randomly selected days at the obstetric department of our hospital, were identified. One hundred and thirty-two women (20.4%, 95% confidence interval (CI): 17.3–23.5) met the criteria for a diagnosis of RLS. The odds ratio (OR) of RLS was, in comparison with women aged <35 years, 1.69 (95% CI 1.14–2.51) in women aged ≥35 years. Subjective insufficient sleep (OR: 2.35, 95% CI 1.27–4.35) and difficulty in initiating sleep (OR: 1.73, 95% CI 1.15–2.63) increased the risk of RLS. This study confirms the high frequency of RLS in pregnant women. The risk of the condition was increased in women aged ≥35 years and in the women reporting sleep-wake disturbances during pregnancy. Impact statement What is already known on this subject? Restless legs syndrome (RLS), a common neurological, sensorimotor disorder, is two/three times more frequent in pregnant women than in the general population. The prevalence of RLS during pregnancy ranges widely, showing differences among populations. What do the results of this study add? This study adds data about the frequency and the risk factors for RLS during pregnancy in a Northern Italian population, rarely considered in epidemiological studies on the syndrome. Older age and sleep-wake disturbances are the main factors associated with the condition. What are the implications of these findings for clinical practice and/or further research? Screening for RLS might be useful for pregnant women to manage the condition. Further research is needed to investigate and define the potential impact of RLS during pregnancy on foetal and maternal health.
Comparative analysis of avian hearts provides little evidence for variation among species with acquired endothermy

Mammals and birds acquired high performance hearts and endothermy during their independent evolution from amniotes with many sauropsid features. A literature review shows that the variation in atrial morphology is greater in mammals than in ectothermic sauropsids. We therefore hypothesized that the transition from ectothermy to endothermy was associated with greater variation in cardiac structure. We tested the hypothesis in 14 orders of birds by assessing the variation in 15 cardiac structures by macroscopic inspection and histology, with an emphasis on the atria as they have multiple features that lend themselves to quantification. We found bird hearts to have multiple features in common with ectothermic sauropsids (synapomorphies), such as the presence of three sinus horns. Convergent features were shared with crocodylians and mammals, such as the cranial offset of the left atrioventricular junction. Other convergent features, like the compact organization of the atrial walls, were shared with mammals only. Pacemaker myocardium, identified by Isl1 expression, was anatomically node‐like (Mallard), thickened (Chicken), or indistinct (Lesser redpoll, Jackdaw). Some features were distinctly avian, (autapomorphies) including the presence of a left atrial antechamber and the ventral merger of the left and right atrial auricles, which was found in some species of parrots and passerines. Most features, however, exhibited little variation. For instance, there were always three systemic veins and two pulmonary veins, whereas among mammals there are 2–3 and 1–7, respectively. Our findings suggest that the transition to high cardiac performance does not necessarily lead to a greater variation in cardiac structure.
Distributed Set-Membership Filtering for Multirate Systems Under the Round-Robin Scheduling Over Sensor Networks

In this paper, the distributed set-membership filtering problem is dealt with for a class of time-varying multirate systems in sensor networks with the communication protocol. For relieving the communication burden, the round-Robin (RR) protocol is exploited to orchestrate the transmission order, under which each sensor node only broadcasts partial information to both the corresponding local filter and its neighboring nodes. In order to meet the practical transmission requirements as well as reduce communication cost, the multirate strategy is proposed to govern the sampling/update rate of the plant, the sensors, and the filters. By means of the lifting technique, the augmented filtering error system is established with a unified sampling rate. The main purpose of the addressed filtering problem is to design a set of distributed filters such that, in the simultaneous presence of the RR transmission protocol, the multirate mechanism, and the bounded noises, there exists a certain ellipsoid that includes all possible error states at each time instant. Then, the desired distributed filter gains are obtained by minimizing such an ellipsoid in the sense of the minimum trace of the weighted matrix. The proposed resource-efficient filtering algorithm is of a recursive form, thereby facilitating the online implementation. A numerical simulation example is given to demonstrate the effectiveness of the proposed protocol-based distributed filter design method.
Learning Theory and Educational Intervention: Producing Meaningful Evidence of Impact Through Layered Analysis.

Like evidence-based medicine, evidence-based education seeks to produce sound evidence of impact that can be used to intervene successfully in the future. The function of educational innovations, however, is much less well understood than the physical mechanisms of action of medical treatments. This makes production, interpretation, and use of educational impact evidence difficult. Critiques of medical education experiments highlight a need for such studies to do a better job of deepening understanding of learning in context; conclusions that "it worked" often precede scrutiny of what "it" was. The authors unpack the problem of representing educational innovation in a conceptually meaningful way. The more fundamental questions of "What is the intended intervention? " and "Did that intervention, in fact, occur? " are proposed as an alternative to the ubiquitous evaluative question of "Did it work? " The authors excavate the layers of intervention-techniques at the surface, principle in the middle, and philosophy at the core-and propose layered analysis as a way of examining an innovation's intended function in context. The authors then use problem-based learning to illustrate how layered analysis can promote meaningful understanding of impact through specification of what was tried, under what circumstances, and what happened as a result. Layered analysis should support innovation design and evaluation by illuminating what principled adaptation of educational technique to local context could look like. It also promotes theory development by enabling more precise description of the learning conditions at work in a given implementation and how they may evolve with broader adoption.
Feasibility of single position endoscopic laser balloon ablation for atrial fibrillation: The open 8 approach

Ablation without shaft repositioning may make the endoscopic laser ablation system (EAS) more like a single shot approach. We tested the feasibility of wide circumferential ablation (WCA; no carina ablation and no shaft repositioning) in an “open 8” pattern for pulmonary vein isolation (PVI).
The neuropsychological profiles of young psychosis patients with and without current cannabis use

ABSTRACT Introduction: Evidence suggests that patients with psychosis who have a history of cannabis use, but currently abstain, demonstrate superior cognitive performance than patients who have never used cannabis. The present study aimed to determine the neurocognitive profiles of patients who are in adolescence or early adulthood, when both illness- and drug-onset typically occur. Methods: Subjects were 24 cannabis-using and 79 cannabis-naïve psychosis patients between 16 and 25 years of age. Patients and controls were administered a neurocognitive battery, indexing estimated pre-morbid intelligence, psychomotor speed, mental flexibility, verbal learning and memory, verbal fluency, sustained attention, motor and mental response, and visuospatial learning and memory. Results: While healthy controls outperformed both patient groups across most cognitive measures, no significant differences between cannabis-using and cannabis-abstinent patients were evident. Conclusion: Evidently although there may be a group of patients who are diagnosed with a non-affective psychosis disorder regardless of external factors (i.e. cannabis use), some may instead have their illness precipitated through cannabis use at a young age, presenting with unique cognitive and symptomatic repercussions later in life. These results demonstrate no cognitive differences between cannabis-using patients and abstinent patients at the time of illness-onset, providing partial support for an alternative pathway to schizophrenia through early cannabis use.
Blood pressure and cognitive performances in middle-aged adults: the Aging, Health and Work longitudinal study

Background: Our objective was to investigate the impact of both prevalent and incident hypertension on cognition in middle-aged individuals followed up for 10 years and to explore the extent to which blood pressure control by antihypertensive drugs could modify this relationship. Method: Three thousand, two hundred and one participants from the Vieillissement Santé Travail (Aging, Health and Work) (VISAT) cohort study, aged 32, 42, 52 and 62 years at baseline were followed up 5 and 10 years later. Blood pressure, antihypertensive medication use as well as memory and speed cognitive performances were assessed at baseline and follow-up. Linear mixed models were used for analyses. Results: At 10-year follow-up, compared with nonhypertensive participants, prevalent hypertensive individuals showed poorer global cognitive performances (&bgr; = −2.99 ± 0.96, P = 0.002 for participants aged 32 or 42 years at baseline and &bgr; = −5.94 ± 1.00, P < 0.001 for those aged 52 or 62). Patients with incident hypertension had poorer global cognitive performances over time compared with patients without hypertension. When considering prevalent hypertension and blood pressure control status by antihypertensive therapy, untreated and uncontrolled hypertension were associated with poorer cognitive performances than controlled and no hypertension (untreated hypertension compared with no hypertension: &bgr; = −5.51 ± 0.75, P < 0.001; uncontrolled hypertension compared with no hypertension: &bgr; = −6.13 ± 1.40, P < 0.001). Conclusion: Our findings showed that both prevalent and incident hypertension are associated with poorer global cognitive function in middle-aged individuals and suggested a potential preventive effect of antihypertensive therapy on cognition. Thus, for brain functioning, heightened efforts to detect hypertension and adequately treat it are of critical importance.
Psychosocial and functional contributors to personal recovery in serious mental illness

Abstract Background: Although recovery-oriented services have been conceptualized to improve personal recovery, related research often focuses on measures of clinical recovery. Identifying the relationships between personal recovery, clinical recovery, and psychosocial variables will inform service components and outcome measurement in recovery-oriented services. Aims: This study sought to determine the connection between personal recovery and two sets of potential contributors: psychosocial variables (i.e., empowerment, resilience, and consumer involvement) and functional indicators of clinical recovery. Method: These relationships were examined by analyzing survey data collected from 266 consumers who are receiving public mental health services in the United States. Results: Empowerment, resilience and psychological involvement were associated with personal recovery. Clinical recovery did not uniquely contribute to personal recovery once psychosocial factors were accounted for. Interactions revealed that the relationship between psychological involvement and personal recovery was stronger for those who had been recently hospitalized, and for those with relatively greater resilience. Conclusions: Results indicate that personal recovery is an essential outcome measure for recovery-oriented services that cannot be replaced by clinical recovery outcome measurement. Additionally, empowerment, resilience, and consumer involvement are key components of recovery, which suggests that services and outcome measures should prioritize incorporation of these constructs.
A reevaluation of the electrophysiological correlates of absolute pitch and relative pitch: No evidence for an absolute pitch-specific negativity

Musicians with absolute pitch effortlessly identify the pitch of a sound without an external reference. Previous neuroscientific studies on absolute pitch have typically had small samples sizes and low statistical power, making them susceptible for false positive findings. In a seminal study, Itoh et al. (2005) reported the elicitation of an absolute pitch-specific event-related potential component during tone listening — the AP negativity. Additionally, they identified several components as correlates of relative pitch, the ability to identify relations between pitches. Here, we attempted to replicate the main findings of Itoh et al.’s study in a large sample of musicians (n = 104) using both frequentist and Bayesian inference. We were not able to replicate the presence of an AP negativity during tone listening in individuals with high levels of absolute pitch, but we partially replicated the findings concerning the correlates of relative pitch. Our results are consistent with several previous studies reporting an absence of differences between musicians with and without absolute pitch in early auditory evoked potential components. We conclude that replication studies form a crucial part in assessing extraordinary findings, even more so in small fields where a single finding can have a large impact on further research.
Measurement of Tumor Antioxidant Capacity and Prediction of Chemotherapy Resistance in Preclinical Models of Ovarian Cancer by Positron Emission Tomography

Purpose: Drug resistance is a major obstacle for the effective treatment of patients with high-grade serous ovarian cancer (HGSOC). Currently, there is no satisfactory way to identify patients with HGSOC that are refractive to the standard of care. Here, we propose the system xc− radiotracer (4S)-4-(3-[18F]fluoropropyl)-l-glutamate ([18F]FSPG) as a non-invasive method to measure upregulated antioxidant pathways present in drug-resistant HGSOC. Experimental Design: Using matched chemotherapy sensitive and resistant ovarian cancer cell lines, we assessed their antioxidant capacity and its relation to [18F]FSPG uptake, both in cells and in animal models of human ovarian cancer. We identified the mechanisms driving differential [18F]FSPG cell accumulation and evaluated [18F]FSPG tumor uptake as predictive marker of treatment response in drug-resistant tumors. Results: High intracellular glutathione (GSH) and low reactive oxygen species corresponded to decreased [18F]FSPG cell accumulation in drug-resistant versus drug-sensitive cells. Decreased [18F]FSPG uptake in drug-resistant cells was a consequence of changes in intracellular cystine, a key precursor in GSH biosynthesis. In vivo, [18F]FSPG uptake was decreased nearly 80% in chemotherapy-resistant A2780 tumors compared with parental drug-sensitive tumors, with nonresponding tumors displaying high levels of oxidized-to-reduced GSH. Treatment of drug-resistant A2780 tumors with doxorubicin resulted in no detectable change in tumor volume, GSH, or [18F]FSPG uptake. Conclusions: This study demonstrates the ability of [18F]FSPG to detect upregulated antioxidant pathways present in drug-resistant cancer. [18F]FSPG may therefore enable the identification of patients with HGSOC that are refractory to standard of care, allowing the transferal of drug-resistant patients to alternative therapies, thereby improving outcomes in this disease.
Pharmacologic Characterization of ALD1910, a Potent Humanized Monoclonal Antibody against the Pituitary Adenylate Cyclase-Activating Peptide

Migraine is a debilitating disease that affects almost 15% of the population worldwide and is the first cause of disability in people under 50 years of age, yet its etiology and pathophysiology remain incompletely understood. Recently, small molecules and therapeutic antibodies that block the calcitonin gene-related peptide (CGRP) signaling pathway have reduced migraine occurrence and aborted acute attacks of migraine in clinical trials and provided prevention in patients with episodic and chronic migraine. Heterogeneity is present within each diagnosis and patient’s response to treatment, suggesting migraine as a final common pathway potentially activated by multiple mechanisms, e.g., not all migraine attacks respond to or are prevented by anti-CGRP pharmacological interventions. Consequently, other unique mechanisms central to migraine pathogenesis may present new targets for drug development. Pituitary adenylate cyclase-activating peptide (PACAP) is an attractive novel target for treatment of migraines. We generated a specific, high-affinity, neutralizing monoclonal antibody (ALD1910) with reactivity to both PACAP38 and PACAP27. In vitro, ALD1910 effectively antagonizes PACAP38 signaling through the pituitary adenylate cyclase-activating peptide type I receptor, vasoactive intestinal peptide receptor 1, and vasoactive intestinal peptide receptor 2. ALD1910 recognizes a nonlinear epitope within PACAP and blocks its binding to the cell surface. To test ALD1910 antagonistic properties directed against endogenous PACAP, we developed an umbellulone-induced rat model of neurogenic vasodilation and parasympathetic lacrimation. In vivo, this model demonstrates that the antagonistic activity of ALD1910 is dose-dependent, retaining efficacy at doses as low as 0.3 mg/kg. These results indicate that ALD1910 represents a potential therapeutic antibody to address PACAP-mediated migraine.