Miracle-dz/UniFAR-FTUs huggingface dataset:
Electrical remodelling precedes heart failure in an endothelin-1-induced model of cardiomyopathy.

AIMS Binary transgenic (BT) mice with doxycycline (DOX)-suppressible cardiac-specific overexpression of endothelin-1 (ET-1) exhibit progressive heart failure (HF), QRS prolongation, and death following DOX withdrawal. However, the molecular basis and reversibility of the electrophysiological abnormalities in this model were not known. Here, we assess the mechanisms underlying ET-1-mediated electrical remodelling, and its role in HF. METHODS AND RESULTS BT vs. non-BT littermate controls were withdrawn from DOX and serially studied with ultrasound biomicroscopy, octapolar catheters, multielectrode epicardial mapping, histopathology, western blot, immunohistochemistry, and qRT-PCR. Abnormalities in ventricular activation and -dV/dt were detected as early as 4 weeks after transgene activation, when the structure and function of the heart remained unaffected. By 8 weeks of ET-1 overexpression, biventricular systolic and diastolic dysfunction, myocardial fibrosis, and cardiomyocyte hypertrophy were observed. Intracardiac and epicardial electrograms revealed prolonged conduction and ventricular activation, reduced -dV/dt, and abnormal atrioventricular nodal function. Within 4 weeks of ET-1 induction, connexin 40 (Cx40) protein and Cx43 mRNA, protein, and phosphorylation levels were reduced by 36, 64, 93, and 69%, respectively; Na(v)1.5 mRNA and protein levels were reduced by 30 and 50%, respectively, as was Na(+) channel conductance. Importantly, the associated electrophysiological abnormalities at this time point were reversible upon suppression of ET-1 overexpression and completely prevented the development of structural and functional remodelling. CONCLUSION ET-1-mediated electrical remodelling correlates with reduced Cx40, Cx43, and Na(v)1.5 expression and decreased Na(+) channel conductance and precedes HF. The sequence and reversibility of this phenotype suggest that a primary abnormality in electrical remodelling may contribute to the pathogenesis of HF.
Fear, Sadness and Hope: Which Emotions Maximize Impact of Anti-Tobacco Mass Media Advertisements among Lower and Higher SES Groups?

Emotive anti-tobacco advertisements can increase quitting. Discrete emotion theories suggest evoking fear may be more effective than sadness; less research has focused on hope. A weekly cross-sectional survey of smokers and recent quitters (N = 7683) measured past-month quit attempts. The main predictor was level of exposure to four different types of anti-tobacco advertisements broadcast in the two months prior to quit attempts: advertisements predominantly evoking fear, sadness, hope, or evoking multiple negative emotions (i.e., fear, guilt, and/or sadness). Greater exposure to fear-evoking advertisements (OR = 2.16, p < .01) increased odds of making a quit attempt and showed similar effectiveness among those in lower and higher SES areas. Greater exposure to advertisements evoking multiple negative emotions increased quit attempts (OR = 1.70, p < .01), but interactions indicated this was driven by those in lower SES, but not higher SES areas. Greater exposure to hope-evoking advertisements enhanced effects of fear-evoking advertisements among those in higher SES, but not lower SES areas. Findings suggest to be maximally effective across the whole population avoid messages evoking sadness and use messages eliciting fear. If the aim is to specifically motivate those living in lower SES areas where smoking rates are higher, multiple negative emotion messages, but not hope-evoking messages, may also be effective.
Overexpression of sorcin in multidrug-resistant human breast cancer

Sorcin is a soluble resistance-related calcium-binding protein, which is expressed in normal mammalian tissues, such as the liver, lungs and heart. It has been observed to be elevated in a number of cancer types, including colorectal, gastric and breast cancer. Its upregulation is usually associated with the development of chemotherapeutic drug resistance. The aim of this study was to evaluate the sorcin expression levels in human serum samples of breast cancer subjects at various stages, and subsequently compare the outcome of neoadjuvant chemotherapy when the sorcin levels fluctuated. In total, 50 subjects were recruited from patients who were admitted to Yantai Yuhunagding Hospital (Yantai, China) and diagnosed with breast cancer. Blood samples prior to and following chemotherapy were assessed using two-dimensional gel electrophoresis (2-DE) and western blot analysis. The 2-DE analysis of the serum samples revealed that sorcin was upregulated in six out of 29 neoadjuvant chemotherapy (NAC)-sensitive patients and, in those who developed multidrug resistance, sorcin was upregulated in 15 out of 21 patients (P<0.01). The differential expression levels of sorcin were confirmed by western blot and immunohistochemical analysis. In conclusion, sorcin expression in the human serum of breast cancer patients who are resistant to NAC was elevated when compared with that of NAC-sensitive patients.
Real-Time Strategy Video Game Experience and Visual Perceptual Learning

Visual perceptual learning (VPL) is defined as long-term improvement in performance on a visual-perception task after visual experiences or training. Early studies have found that VPL is highly specific for the trained feature and location, suggesting that VPL is associated with changes in the early visual cortex. However, the generality of visual skills enhancement attributable to action video-game experience suggests that VPL can result from improvement in higher cognitive skills. If so, experience in real-time strategy (RTS) video-game play, which may heavily involve cognitive skills, may also facilitate VPL. To test this hypothesis, we compared VPL between RTS video-game players (VGPs) and non-VGPs (NVGPs) and elucidated underlying structural and functional neural mechanisms. Healthy young human subjects underwent six training sessions on a texture discrimination task. Diffusion-tensor and functional magnetic resonance imaging were performed before and after training. VGPs performed better than NVGPs in the early phase of training. White-matter connectivity between the right external capsule and visual cortex and neuronal activity in the right inferior frontal gyrus (IFG) and anterior cingulate cortex (ACC) were greater in VGPs than NVGPs and were significantly correlated with RTS video-game experience. In both VGPs and NVGPs, there was task-related neuronal activity in the right IFG, ACC, and striatum, which was strengthened after training. These results indicate that RTS video-game experience, associated with changes in higher-order cognitive functions and connectivity between visual and cognitive areas, facilitates VPL in early phases of training. The results support the hypothesis that VPL can occur without involvement of only visual areas. SIGNIFICANCE STATEMENT Although early studies found that visual perceptual learning (VPL) is associated with involvement of the visual cortex, generality of visual skills enhancement by action video-game experience suggests that higher-order cognition may be involved in VPL. If so, real-time strategy (RTS) video-game experience may facilitate VPL as a result of heavy involvement of cognitive skills. Here, we compared VPL between RTS video-game players (VGPs) and non-VGPs (NVGPs) and investigated the underlying neural mechanisms. VGPs showed better performance in the early phase of training on the texture discrimination task and greater level of neuronal activity in cognitive areas and structural connectivity between visual and cognitive areas than NVGPs. These results support the hypothesis that VPL can occur beyond the visual cortex.
Proliferation and Differentiation of Rat Osteoporosis Mesenchymal Stem Cells (MSCs) after Telomerase Reverse Transcriptase (TERT) Transfection

Background The aim of this study was to determine whether MSC are excellent materials for MSCs transplantation in the treatment of osteoporosis. Material/Methods We studied normal, osteoporosis, and TERT-transfected MSC from normal and osteoporosis rats to compare the proliferation and osteogenic differentiation using RT-PCR and Western blot by constructing an ovariectomized rat model of osteoporosis (OVX). The primary MSC from model rats were extracted and cultured to evaluate the proliferation and differentiation characteristics. Results MSCs of osteoporosis rats obviously decreased in proliferation ability and osteogenic differentiation compared to that of normal rats. In contrast, in TERT-transfected MSC, the proliferation and differentiation ability, and especially the ability of osteogenic differentiation, were significantly higher than in osteoporosis MSC. Conclusions TERT-transfected MSCs can help osteoporosis patients in whom MSC proliferation and osteogenic differentiation ability are weak, with an increase in both bone mass and bone density, becoming an effective material for autologous transplantation of MSCs in further treatment of osteoporosis. However, studies are still needed to prove the in vivo effect, biological safety, and molecular mechanism of TERT-osteoporosis treatment. Additionally, because the results are from an animal model, more research is needed in generalizing rat model findings to human osteoporosis patients.
Differing associations between Aβ accumulation, hypoperfusion, blood–brain barrier dysfunction and loss of PDGFRB pericyte marker in the precuneus and parietal white matter in Alzheimer's disease

Recent studies implicate loss of pericytes in hypoperfusion and blood–brain barrier (BBB) leakage in Alzheimer's disease (AD). In this study, we have measured levels of the pericyte marker, platelet-derived growth factor receptor-β (PDGFRB), and fibrinogen (to assess blood–brain barrier leakage), and analyzed their relationship to indicators of microvessel density (von Willebrand factor level), ante-mortem oxygenation (myelin-associated glycoprotein:proteolipid protein-1 ratio and vascular endothelial growth factor level), Aβ level and plaque load, in precuneus and underlying white matter from 49 AD to 37 control brains. There was reduction in PDGFRB and increased fibrinogen in the precuneus in AD. These changes correlated with reduction in oxygenation and with plaque load. In the underlying white matter, increased fibrinogen correlated with reduced oxygenation, but PDGFRB level was unchanged. The level of platelet-derived growth factor-ββ (PDGF-BB), important for pericyte maintenance, was increased in AD but mainly in the insoluble tissue fraction, correlating with insoluble Aβ level. Loss of the PDGFRB within the precuneus in AD is associated with fibrinogen leakage and reduced oxygenation, and related to fibrillar Aβ accumulation. In contrast, fibrinogen leakage and reduced oxygenation of underlying white matter occur independently of loss of PDGFRB, perhaps secondary to reduced transcortical perfusion.
Drought and Cooler Temperatures Are Associated with Higher Nest Survival in Mountain Plovers

Native grasslands have been altered to a greater extent than any other biome in North America. The habitats and resources needed to support breeding performance of grassland birds endemic to prairie ecosystems are currently threatened by land management practices and impending climate change. Climate models for the Great Plains prairie region predict a future of hotter and drier summers with strong multiyear droughts and more frequent and severe precipitation events. We examined how fluctuations in weather conditions in eastern Colorado influenced nest survival of an avian species that has experienced recent population declines, the Mountain Plover (Charadrius montanus). Nest survival averaged 27.2% over a 7-yr period (n = 936 nests) and declined as the breeding season progressed. Nest survival was favored by dry conditions and cooler temperatures. Projected changes in regional precipitation patterns will likely influence nest survival, with positive influences of predicted declines in summer rainfall yet negative effects of more intense rain events. The interplay of climate change and land use practices within prairie ecosystems may result in Mountain Plovers shifting their distribution, changing local abundance, and adjusting fecundity to adapt to their changing environment. RESUME. Les prairies naturelles ont ete plus grandement modifiees que tout autre biome en Amerique du Nord. L’habitat et les ressources necessaires pour favoriser la performance reproductrice des oiseaux de prairie endemiques de ces ecosystemes sont actuellement menaces par les pratiques de gestion des terres et les changements climatiques imminents. Les modeles climatiques pour les prairies des Grandes Plaines prevoient des etes plus chauds et plus secs, des secheresses severes durant plusieurs annees et des evenements de precipitation plus frequents et intenses que ce qu’on observe presentement. Nous avons examine les effets des fluctuations des conditions meteorologiques dans l’est du Colorado sur la survie des nids chez une espece aviaire ayant subi un recent declin des populations, le Pluvier montagnard (Charadrius montanus). Le taux de survie des nids s’elevait a 27,2 % en moyenne sur une periode de 7 ans (n = 936 nids) et diminuait a mesure que progressait la saison de reproduction. La survie des nids etait superieure quand les conditions etaient seches et les temperatures fraiches. Les changements prevus dans les tendances regionales des precipitations influenceront vraisemblablement la survie des nids : tandis que la diminution des precipitations estivales prevue entrainera un effet positif sur la survie, les evenements de precipitation plus intenses prevus auront, quant a eux, un effet negatif. L’interaction des changements climatiques et des pratiques d’utilisation des sols dans les ecosystemes de prairie amenera peut-etre le Pluvier montagnard a modifier sa repartition, son abondance locale et sa fecondite pour s’adapter a l’environnement changeant.
Lowering the Cost of Improved Cross-Lingual Sentiment Analysis by

In this work1, we take a two pronged approach to improving cross-lingual sentiment analysis. First, using a new technique, we show that word embeddings can be enriched for sentiment information without the need of a labeled corpora; this enrichment improves performance across the board in both sentiment and non-sentiment-related tasks. Second, we study how a linear transformation that can effectively leverage embeddings and English sentiment knowledge without the need for accurate translation. Across a series of diverse tasks, we show that this transformation is effective in analyzing languages with scarce data, despite the sub-par translation accuracy, thus making sentiment and related analyses for many languages inexpensive. 1This work is based on two papers: i)(Abdalla and Hirst, 2017) and ii)(Abdalla et al., 2018)
The mechanism of formation of bony spurs (enthesophytes) in the achilles tendon.

OBJECTIVE To investigate the early stages in the formation of bony spurs in relation to normal enthesis development. METHODS Histologic sections of rat Achilles tendons, stained with toluidine blue or Masson's trichrome, were examined in animals ranging from 2 weeks to 1 year of age. Further material prepared for immunohistochemistry was labeled with monoclonal antibodies for laminin and type IV collagen to highlight the presence of small blood vessels at the enthesis. Sections of small spurs from the Achilles tendons of elderly humans were also examined for comparison. RESULTS As a part of normal development, bone grows into the Achilles tendon as the calcaneus enlarges. Ossification is preceded by vascular invasion, which occurs along rows of enthesis fibrocartilage cells. Small bony spurs develop when ossification at one point on the enthesis outstrips that on either side. CONCLUSION Bony spurs can develop in the Achilles tendon without the need for preceding microtears or any inflammatory reaction, and they form by endochondral ossification of enthesis fibrocartilage. The increased surface area created at the tendon-bone junction may be an adaptive mechanism to ensure the integrity of the interface in response to increased mechanical loads.
Synaptic adhesion protein ELFN1 is a selective allosteric modulator of group III metabotropic glutamate receptors in trans

Significance G protein-coupled receptors (GPCRs) continue to be the pharmaceutical target of over one-third of FDA-approved drugs, yet our understanding of GPCR function has been overwhelmingly limited to the study of intracellular effectors. It is emerging that GPCRs also associate with a variety of extracellular proteins, yet the functional consequences of these interactions have been ill defined for the lack of robust approaches to measure them. In this study, we develop a unique assay platform and provide an example of transcellular modulation of GPCR properties by association with a synaptic adhesion molecule. Functional characterization of the GPCR interactome has been focused predominantly on intracellular interactions, yet GPCRs are increasingly found in complex with extracellular proteins. Extracellular leucine-rich repeat fibronectin type III domain containing 1 (ELFN1) was recently reported to physically anchor mGluR6 and mGluR7 across retinal and hippocampal synapses, respectively; however, the consequence of transsynaptic interactions on properties and pharmacology of these receptors are unknown. In the current study, we explore the effects of ELFN1 on mGluR signaling and pharmacology. First, we established the binding specificity of ELFN1 and found it to be recruited selectively to all group III mGluRs (mGluR4, mGluR6, mGluR7, and mGluR8), but not other mGluR species. Using site-directed mutagenesis we mapped binding determinants of this interaction to two distinct sites on the ELFN1 ectodomain. To evaluate functional aspects of the interaction, we developed a transcellular signaling assay in reconstituted HEK293 cells which monitors changes in mGluR activity in one cell following its exposure to separate ELFN1-containing cells. Using this platform, we found that ELFN1 acts as an allosteric modulator of class III mGluR activity in suppressing cAMP accumulation: altering both agonist-induced and constitutive receptor activity. Using bioluminescence resonance energy transfer-based real-time kinetic assays, we established that ELFN1 alters the ability of mGluRs to activate G proteins. Our findings demonstrate that core properties of class III mGluRs can be altered via extracellular interactions with ELFN1 which serves as a transsynaptic allosteric modulator for these receptors. Furthermore, our unique assay platform opens avenues for exploring transcellular/transsynaptic pharmacology of other GPCR transcomplexes.
“The Work Must Go On”

The Netherlands is characterized by extensive national work–life regulations relative to the United States. Yet, Dutch employees do not always take advantage of existing work–life policies. Individual and focus group interviews with employees and managers in three (public and private) Dutch organizations identified how employee and managerial communication contributed to acquired rules concerning work–life policies and the interpretation of allocative and authoritative resources for policy enactment. Analyses revealed differences in employees’ and managers’ resistance to policy, the binds and dilemmas experienced, and the coordination of agreements and actions to complete workloads. There are also differences between public and private contexts in the enactment of national and organizational policies, revealing how national (e.g., gender) and organizational (e.g., concertive control) mechanisms play out in employee and managerial communication that determine the use of work–life policies.
Patient-controlled Interscalene Analgesia with Ropivacaine 0.2%Versus Patient-controlled Intravenous Analgesia after Major Shoulder Surgery: Effects on Diaphragmatic and Respiratory Function

Background The authors compared the effects of patient-controlled interscalene analgesia (PCIA) with ropivacaine 0.2% and patient-controlled intravenous analgesia (PCIVA) with opioids on hemidiaphragmatic excursion and respiratory function after major shoulder surgery. Methods Thirty-five patients scheduled for elective major shoulder surgery were prospectively randomized to receive either PCIA or PCIVA. All patients received an interscalene block before surgery. In the PCIA group, a catheter was introduced between the anterior and middle scalene muscles. Six hours after the initial block, patients received for 48 h either a continuous infusion of 0.2% ropivacaine through the interscalene catheter at a rate of 5 ml/h plus a bolus dose of 3 or 4 ml with a lockout time of 20 min (PCIA group) or a continuous intravenous infusion of nicomorphine at a rate or 0.5 mg/h plus a bolus dose of 2 or 3 mg with a lockout time of 20 min (PCIVA group). Hemidiaphragmatic excursion and respiratory function were assessed with the patient in a 45° semirecumbent position the day before the operation and 20 min (in the operating room), 24 h, and 48 h after the initial block by means of ultrasonography and spirometry, respectively. Pain relief was regularly assessed, side effects were noted, and patient satisfaction was rated 6 h after the end of the study. Results Hemidiaphragmatic excursion was similar in the two groups 20 min after interscalene block. Hemidiaphragmatic excursion was increased in the PCIA group on the nonoperated side 24 and 48 h after the interscalene block (P < 0.05). Pulmonary function was similar in the two groups at each time. Pain was better controlled in the PCIA group at 12 and 24 h (P < 0.05). The incidence of nausea and vomiting were 5.5%versus 60% for the PCIA and PCIVA groups, respectively (P < 0.05). Patient satisfaction was greater in the PCIA group (P < 0.05). Conclusions The use of PCIA or PCIVA techniques to provide analgesia after major shoulder surgery is associated with similar effects on respiratory function. In the PCIA group, hemidiaphragmatic excursion showed a significantly greater amplitude 24 and 48 h after the initial block on the nonoperated side. The PCIA technique provided better pain control, a lower incidence of side effects, and a higher degree of patient satisfaction.
Mindfulness: An effective coaching tool for improving physical and mental health

Purpose: This article provides an overview of the mechanisms of action, evidence base, and practice of mindfulness, with an emphasis on how to easily incorporate this valuable skill into practice. Data sources: PubMed, CINAHL, PsychInfo Databases. Conclusions: Conscious attention to the present moment in a receptive way is known as mindfulness. A growing body of research indicates that mindfulness can be taught and cultivated to improve physical and mental health. Implications for practice: Accordingly, as part of the coaching competency, mindfulness can be practiced and taught by advanced practice nurses to support lifestyle and behavioral changes, decrease perceived stress, enhance quality of life, and, ultimately, improve health and health outcomes.