Miracle-dz/UniFAR-FTUs huggingface dataset:
Cardioprotective Effects of the Novel Compound Vastiras in a Preclinical Model of End-Organ Damage

Supplemental Digital Content is available in the text. Cardiac hypertrophy and renal damage associated with hypertension are independent predictors of morbidity and mortality. In a model of hypertensive heart disease and renal damage, we tested the actions of continuous administration of Vastiras, a novel compound derived from the linear fragment of ANP (atrial natriuretic peptide), namely pro-ANP31–67, on blood pressure and associated renal and cardiac function and remodeling. Of note, this peptide, unlike the ring structured forms, does not bind to the classic natriuretic peptide receptors. Dahl/Salt–Sensitive rats fed a 4% NaCl diet for 6 weeks developed hypertension, cardiac hypertrophy, and renal damage. Four weeks of treatment with 50 to 100 ng/kg per day of Vastiras exhibited positive effects on renal function, independent of blood pressure regulation. Treated rats had increased urine excretion, natriuresis, and enhanced glomerular filtration rate. Importantly, these favorable renal effects were accompanied by improved cardiac structure and function, including attenuated cardiac hypertrophy, as indicated by decreased heart weight to body weight ratio, relative wall thickness, and left atrial diameter, as well as reduced fibrosis and normalized ratio of the diastolic mitral inflow E wave to A wave. A renal subtherapeutic dose of Vastiras (25 ng/kg per day) induced similar protective effects on the heart. At the cellular level, cardiomyocyte size and t-tubule density were preserved in Vastiras-treated compared with untreated animals. In conclusion, these data demonstrate the cardiorenal protective actions of chronic supplementation of a first-in-class compound, Vastiras, in a preclinical model of maladaptive cardiac hypertrophy and renal damage induced by hypertension.
Interaction of intracellular hydrogen peroxide accumulation with nitric oxide production in abscisic acid signaling in guard cells

ABSTRACT Reactive oxygen species and nitric oxide (NO•) concomitantly play essential roles in guard cell signaling. Studies using catalase mutants have revealed that the inducible and constitutive elevations of intracellular hydrogen peroxide (H2O2) have different roles: only the inducible H2O2 production transduces the abscisic acid (ABA) signal leading stomatal closure. However, the involvement of inducible or constitutive NO• productions, if exists, in this process remains unknown. We studied H2O2 and NO• mobilization in guard cells of catalase mutants. Constitutive H2O2 level was higher in the mutants than that in wild type, but constitutive NO• level was not different among lines. Induced NO• and H2O2 levels elicited by ABA showed a high correlation with each other in all lines. Furthermore, NO• levels increased by exogenous H2O2 also showed a high correlation with stomatal aperture size. Our results demonstrate that ABA-induced intracellular H2O2 accumulation triggers NO• production leading stomatal closure. Abbreviations ABA: abscisic acid; CAT: catalase; cGMP: cyclic guanosine monophosphate; DAF-2DA: 4,5-diaminofluorescein-2 diacetate; H2DCF-DA: 2ʹ,7ʹ-dichlorodihydrofluorescein diacetate; MeJA: methyljasmonate; NOS: nitric oxide synthetase; NR: nitrate reductase; POX: peroxidase; ROS: reactive oxygen species; SNAP: S-nitroso-N-acetyl-DL-penicillamine; SNP: sodium nitroprusside; NOX: NADP(H) oxidase. GRAPHICAL ABSTRACT ABA-induced nitric oxide (NO•) production in guard cells is associated with preceding hydrogen peroxide (H2O2) production that is decayed by catalase (CAT).
Population genetic structure and phylogeography of the greater horseshoe bat (Rhinolophus ferrumequinum) along Alborz and Zagros Mts. in Iran

Abstract In this paper, we investigate the genetic structure and phylogeography of Rhinolophus ferrumequinum, using the mitochondrial cytochrome b gene (1017 bp) in Iran and adjacent regions. The total haplotype and nucleotide diversity are 0.63 ± 0.055 and 0.0021 ± 0.00017, respectively which suggest that R. ferrumequinum exhibits low genetic diversity. AMOVA analysis shows that more variation of genetic differentiation is present among populations of phylogenetic groupings than within populations. Our phylogenetic results support the monophyly of R. ferrumequinum and suggest this taxon comprises three allopatric/parapatric phylogroups that are distributed in Europe-western Turkey, eastern Turkey-northern Iran, and southern Iran. The Europe-western Turkey lineage (clade 2) split from the eastern Turkey-Iran lineage (clade 1) during the middle Pleistocene (0.8534 (ca.I)−0.6454 (ca.II) Ma). The divergence time among subclades A and B occurred during the mid‐Pleistocene (0.4849 (ca.I)−0.369 (ca.II) Ma). All phylogenetic analyses also indicate that the Iranian and eastern Turkey R. ferrumequinum diverged from Europe and western Turkey R. ferrumequinum, with the mean percentage sequence differences ranging from 0.92%−0.75% between them. We infer that long-term isolation of R. ferrumequinum in spatially distinct refugia in parts of southwestern and northeastern Iran has promoted distinct phylogeographic lineages during the Pleistocene.
Complex electrical spiking activity in resistive switching nanostructured Au two-terminal devices

Networks of nanoscale objects are the subject of increasing interest as resistive switching systems for the fabrication of neuromorphic computing architectures. Nanostructured films of bare gold clusters produced in gas phase with thickness well beyond the electrical percolation threshold, show a non-ohmic electrical behavior and resistive switching, resulting in groups of current spikes with irregular temporal organization. Here we report the systematic characterization of the temporal correlations between single spikes and spiking rate power spectrum of nanostructured Au two-terminal devices consisting of a cluster-assembled film deposited between two planar electrodes. By varying the nanostructured film thickness we fabricated two different classes of devices with high and low initial resistance respectively. We show that the switching dynamics can be described by a power law distribution in low resistance devices whereas a bi-exponential behavior is observed in the high resistance ones. The measured resistance of cluster-assembled films shows a 1 / f α scaling behavior in the range of analyzed frequencies. Our results suggest the possibility of using cluster-assembled Au films as components for neuromorphic systems where a certain degree of stochasticity is required.
Neuroinflammation Mediated by GMF Exacerbates Neuronal Injury in an in vitro Model of Traumatic Brain Injury.

Traumatic brain injury (TBI) is the primary cause of death and disability affecting over 10 million people in the industrialized world. TBI causes a wide spectrum of secondary molecular and cellular complications in the brain. However, the pathological events are still not yet fully understood. Previously, we have shown that the glia maturation factor (GMF) is a mediator of neuroinflammation in neurodegenerative diseases. To identify the potential molecular pathways accompanying TBI, we used an in vitro cell culture model of TBI. A standardized injury was induced by scalpel cut through a mixed primary cell culture of astrocytes; microglia and neurons obtained from both wild type (WT) and GMF-deficient (GMF-KO) mice. Cell culture medium and whole-cell lysates were collected at 24, 48 and 72 h after the scalpel cuts injury and probed for oxidative stress using immunofluorescence analysis. Results showed that oxidative stress markers such as glutathione and glutathione peroxidase were significantly reduced while release of cytosolic enzyme lactate dehydrogenase (LDH) along with nitric oxide and prostaglandin E2 were significantly increased in injured WT cells compared with injured GMF-KO cells. In addition, injured WT cells showed increased levels of oxidation product 4-hydroxynonenal (4-HNE) and 8-Oxo-2'-deoxyguanosine (8-OhdG) as compared with injured GMF-KO cells. Furthermore, we found that injured WT cells showed a significantly increased expression of glial fibrillary acidic protein, ionized calcium binding adaptor molecule 1, (GFAP, IBA1), phosphorylated Ezrin/Radixin/Moesin (pERM) proteins and reduced microtubule associated protein (MAP2) expression as compared with injured GMF-KO cells after injury. Collectively, our results demonstrate that GMF exacerbates the oxidative stress - mediated neuroinflammation that could be brought about by TBI-induced astroglial activation.
A conceptual model describing mechanisms for how yoga practice may support positive embodiment

ABSTRACT Yoga practice has been associated with various indices of positive embodiment in correlational and intervention studies. Yet, systematic, theoretically-grounded models detailing specific mechanisms by which yoga supports positive embodiment are lacking. In this article, we present a conceptual model that describes mechanisms (i.e., mediators and moderators) that can be used to guide research to help answer how, for whom, and under what conditions yoga practice may promote positive embodiment. Based on existing theoretical frameworks and empirical findings, this model suggests that (a) yoga practice may cultivate embodying experiences during yoga (e.g., state mindfulness), (b) these embodying experiences may build stable embodying experiences that generalize beyond the yoga context (e.g., trait mindfulness), and (c) these stable embodying experiences may then promote embodying practices (e.g., mindful self-care). This mediational chain is likely moderated by the yoga context (e.g., instructional focus, presence of mirrors, diversity of bodies represented) and yoga practitioners’ social identities (e.g., body size, physical limitations), social and personal histories (e.g., experiences with weight stigma and trauma), and personality traits and motives (e.g., body comparison, appearance-focused motives to practice yoga). Using the structure of this conceptual model, we offer researchers ideas for testable models and study designs that can support them.
Craving is everything: An eye-tracking exploration of attentional bias in binge drinking

Background: Attentional bias towards alcohol-related stimuli is a core characteristic of severe alcohol use disorders (AUD), directly linked to clinical variables (e.g. alcohol consumption, relapse). Nevertheless, the extent of this bias in subclinical populations remains poorly documented. This is particularly true for binge drinking, an alcohol consumption pattern highly prevalent in youth, characterised by an alternation between excessive intakes and withdrawal periods. Aims: We used eye-tracking to: (a) measure attentional bias in binge drinking, (b) determine its time course by dissociating early/late processing stages, (c) clarify its specificity for alcohol-related stimuli compared to other appetitive stimulations and (d) explore its modulation by current craving intensity. Methods: Binge drinkers (n=42) and matched controls (n=43) performed a visual probe task, requiring visual targets preceded by pairs of pictures to be processed, with three conditions (i.e. alcohol vs. soft drink, alcohol vs. high-calorie food, high-calorie food vs. low-calorie food). Results: No group difference was observed for early processing (i.e. first area of interest visited). Dwell times highlighted a bias towards soft drinks and healthy food among controls, without any global bias towards alcohol in binge drinkers. Centrally, a comparison of binge drinkers with low versus high current craving intensity indicated that binge drinking was associated with a bias towards alcohol and high-calorie food only in the presence of a high craving towards these stimuli. Conclusion: Attentional bias towards alcohol reported in severe AUD is only found in binge drinkers in the presence of high craving and is generalised to other appetitive cues.
Factors facilitating recovery following severe traumatic brain injury: A qualitative study

ABSTRACT Given the significant impact of severe traumatic brain injury (TBI), understanding factors influencing recovery is critical to inform prognostication and treatment planning. Previous research has focussed primarily on factors negatively associated with outcome, with less focus on factors facilitating the recovery process. The current qualitative study examined positive factors identified for recovery by individuals who had sustained severe TBI three years earlier. Semi-structured interviews were conducted with nine participants with TBI and 16 close-others. Participants were asked to identify factors about themselves (or the injured individual), those around them, and the care they received that they felt were positive for recovery. Using reflexive thematic analysis, three themes were identified as positive for recovery after a TBI. Having a support network included social supports such as family and friends, and receiving other funded/non-funded assistance towards improving independence and participation. Being positive and engaged included being able to participate, being positive, using compensatory strategies, and becoming fit, healthy and happy. Getting good care included patients perceiving they had a comprehensive and good quality hospital experience, and access to multidisciplinary outpatient services. A focus on enhancing these positive environmental, personal and service factors in service provision may enhance outcomes following severe TBI.
Reproducibility of objectively measured physical activity: Reconsideration needed

ABSTRACT Reliability of accelerometer-determined physical activity (PA), and thus the required length of a monitoring period, appears to depend on the analytic approach used for its calculation. We compared reliability of objectively measured PA using different resolution of data in a sample of 221 Norwegian 2–6-year-old children providing 2–3 valid 14-day periods of accelerometer monitoring (ActiGraph GT3X+) during September–October, January–February, and May–June 2015–2016. Reliability (intra-class correlation [ICC]) was measured for 1–14 days of monitoring across the measurement periods using linear mixed effect modelling. These results were compared to reliability estimated using different resolution of data using the Spearman–Brown formula. The measured reliability improved only marginally with increased monitoring length and levelled off after 5–6 days. Estimated reliability differed substantially when derived from different resolution of data: 3.9–5.4, 6.7–9.2, 13.4–26.7 and 26.3–87.7 days of monitoring was required to achieve an ICC = 0.80 using an hour-by-hour, a day-by-day, a week-by-week and a period-by-period approach, respectively. Reliability could not be correctly estimated from any single resolution of data. We conclude that reconsideration is needed with regard to how reproducibility of objectively measured PA is analysed and interpreted.
A systematic review of morbidities suggestive of the multiple sclerosis prodrome.

Introduction: The identification of a prodromal phase in multiple sclerosis (MS) could have major implications for earlier recognition and management of MS. The authors conducted a systematic review assessing studies of morbidities before, or at, MS onset or diagnosis.Areas covered: Two independent reviewers searched Medline, Embase, Psycinfo and CINAHL from inception to February 8th, 2019. To be eligible, studies had to be published in English and report the relative occurrence of at least one morbidity or symptom before, or at, MS onset or diagnosis among MS cases in comparison to a control group not known to have MS. Findings were narratively synthesized. Study quality was assessed using the Newcastle-Ottawa scale (NOS, maximum score 9). Expert opinion: Twenty-nine studies were included, which comprised 83,590 MS cases and 396,343 controls. Most were case-control studies (25/29), 8/29 were of high quality (NOS≥8) and 19/29 examined the period before MS symptom onset. Most studies assessing anxiety, depression, migraine and lower cognitive performance found these conditions to be more prevalent before MS onset or diagnosis relative to controls. There was limited evidence to implicate other conditions. Thus, there is evidence that anxiety, depression, migraine and lower cognitive performance form part of the MS prodrome.
Sub-surface H2S detection by a Surface Acoustic Wave passive wireless sensor interrogated with a ground penetrating radar.

Long-term monitoring of organic pollutants in the soil is a major environmental challenge. We propose to meet this issue by the development of a polymer dedicated to selectively react with H2S, coating surface acoustic wave transducers designed as passive cooperative targets with the compound, and probing their response using Ground Penetrating RADAR, thus providing the capability to monitor the presence of H2S in the subsurface environment. The selectivity is brought by including lead(II) cation in a reticulated polymer matrix which can be deposited as a thin layer on a surface acoustic wave sensor. We demonstrate a signal enhancement mechanism in which water absorption magnifies the signal detection, making the sensor most sensitive to H2S in an underground environment saturated with moisture.
How I treat steroid-refractory acute graft-versus-host disease.

Steroid-resistant or refractory acute GVHD (SR-aGVHD) poses one of the most vexing challenges faced by providers who care for patients after allogeneic hematopoietic cell transplantation. For the past 4 decades, research in the field been driven by the premise that persistent GVHD results from inadequate immunosuppression. Accordingly, most efforts to solve this problem have relied on retrospective or prospective studies testing agents that have direct or indirect immunosuppressive effects. Retrospective studies far outnumber prospective studies, and no controlled prospective trial has shown superior results for any agent over others. Truth be told, we do not know how to treat SR-aGVHD. Preclinical work during the past decade has provided fresh insights into the pathogenesis of acute GVHD, and translation of these insights toward development of more effective treatments for patients with SR-aGVHD has at last begun. Given the limited state of current knowledge, this "How I Treat" review highlights the overriding imperative to avoid harm in caring for patients with SR-aGVHD. Prospective trials that are widely available are urgently needed to advance the field.
Role of body condition score and adiponectin expression in the progression of canine mammary carcinomas

Abstract Obesity has been identified as a risk factor for developing breast cancer in post‐menopausal period in humans and has been suspected to be associated with a worse prognosis also in the bitch. The aims of this study were to investigate the association between body condition score (BCS) and the prognosis of canine mammary carcinomas (CMCs) and the relationships between adiponectin expression and tumour behaviour. Seventy‐three bitches with tubular, tubulopapillary, solid or complex carcinomas were included in the present study. For each dog, evaluation of BCS was conducted using a nine‐point BCS system and the study population was divided into normal weight (4–5/9 points; n = 42), overweight (6–7/9 points; n = 19) and obese (8–9/9 points; n = 12). Type of diet (commercial, homemade or mixed) was recorded. After surgical excision, histological type, tumour size and nodal status were assessed and adiponectin expression was determined and quantified by immunohistochemistry and morphometric analysis. CMC histotype was not correlated with BCS, while a positive correlation between BCS and histological grade (p < .01) was observed. Overweight and obese bitches combined showed a shorter cancer‐specific survival than normal weighted bitches (p < .01). Bitches fed with a homemade diet had a higher BCS than dogs fed with a commercial one, although no relationship was observed between diet and cancer‐specific survival. Thirty‐six CMCs scored positive for adiponectin expression (49%), but no correlation was found between the hormone expression and either CMC characteristics or prognosis. In conclusion, a higher BCS seems to be related with a higher prevalence of more aggressive CMCs and negatively affects the survival time in bitches with these mammary tumours.
Annexin A1 Expression Capacity as a Determinant for Disease Severity in Crohn’s Disease

Introduction: Crohn’s disease (CD) is characterized by relapsing intestinal inflammation. The anti-inflammatory protein annexin A1 (ANXA1) has been linked to inflammatory processes in the gut. Objective: To examine ANXA1 expression patterns in the inflamed intestine of patients with CD and associate ANXA1 expression capacity with disease characteristics. Methods: Surgical specimens of patients with CD operated between 2003 and 2015 were examined. Immunohistochemistry and immunofluorescence were performed to delineate ANXA1 expression. Those with pronounced ANXA1 expression were included in further analysis by qPCR. ANXA1 mRNA expression ratio of the inflamed to non-inflamed tissue was determined and defined as expression capacity of the tissue. Depending on their expression capacity, patients were divided into 2 groups (ANXA1-low vs. ANXA1-high), which were associated with clinical characteristics. Results: Immunohistochemical ANXA1 expression was localized in inflamed regions of the intestine. In immunofluorescence, ANXA1 costained with myeloperoxidase as neutrophil marker, CD4 and CD8 as T cell marker but not CD20 as B cell marker or CD68 as macrophage marker. In qPCR, ANXA1 mRNA expression was upregulated by 20-fold in inflamed to noninflamed tissues. Patients with higher intrinsic ANXA1 expression capacity had significantly less severity of inflammation. Furthermore, the ANXA1-high group had significantly more locally restricted disease (p = 0.0070), more stricturating disease (p = 0.0037), and was less frequently treated by preoperative steroid therapy (p = 0.030). Conclusions: ANXA1 expression was strongly associated with intestinal inflammation and expressed in T cells and neutrophils of the CD tissues. Patients with higher intrinsic ANXA1 expression capacity of the inflamed tissue presented milder inflammatory changes and indolent clinical course.
Novel Emerging Therapies for Erectile Dysfunction

Currently, several treatments exist for the improvement of erectile dysfunction (ED). These include medical therapies such as phosphodiesterase type 5 inhibitors (PDE5-Is), invasive methods such as intracavernosal injection therapy of vaso-active substances, vacuum erection devices, and penile prosthesis implants. However, the percentage of patients that are unresponsive to available treatments and who drop out from treatments remains high. Current evidence reveals that the pathogenesis of ED is related to multiple factors including underlying comorbidities, previous surgery, and psychological factors. Diverse approaches using novel molecular pathways or new technologies have been tested as potential therapeutic options for difficultto-treat ED populations. Melanocortin receptor agonist, a centrally acting agent, showed promising results by initiating erection without sexual stimulation in non-responders to PDE5-Is. Recent clinical and pre-clinical studies using human tissues suggested that new peripherally acting agents including the Max-K channel activator, guanylate cyclase activator, and nitric oxide donor could be potential therapies either as a monotherapy or in combination with PDE5-Is in ED patients. According to several clinical trials, regeneration therapy using stem cells showed favorable data in men with diabetic or post-prostatectomy ED. Low-intensity shock wave therapy also demonstrated promising results in patients with vasculogenic ED. There are growing evidences which suggest the efficacy of these emerging therapies, though most of the therapies still need to be validated by well-designed clinical trials. It is expected that, should their long-term safety and efficacy be proven, the emerging treatments can meet the needs of patients hitherto unresponsive to or unsatisfied by current therapies for ED.