Miracle-dz/UniFAR-FTUs huggingface dataset:
Unloading the Left Ventricle Before Reperfusion in Patients With Anterior ST-Segment–Elevation Myocardial Infarction: A Pilot Study Using the Impella CP

Background: In ST-segment–elevation myocardial infarction (STEMI), infarct size correlates directly with heart failure and mortality. Preclinical testing has shown that, in comparison with reperfusion alone, mechanically unloading the left ventricle (LV) before reperfusion reduces infarct size and that 30 minutes of unloading activates a cardioprotective program that limits reperfusion injury. The DTU-STEMI pilot trial (Door-To-Unload in STEMI Pilot Trial) represents the first exploratory study testing whether LV unloading and delayed reperfusion in patients with STEMI without cardiogenic shock is safe and feasible. Methods: In a multicenter, prospective, randomized exploratory safety and feasibility trial, we assigned 50 patients with anterior STEMI to LV unloading by using the Impella CP followed by immediate reperfusion (U-IR) versus delayed reperfusion after 30 minutes of unloading (U-DR). The primary safety outcome was a composite of major adverse cardiovascular and cerebrovascular events at 30 days. Efficacy parameters included the assessment of infarct size by using cardiac magnetic resonance imaging. Results: All patients completed the U-IR (n=25) or U-DR (n=25) protocols with respective mean door-to-balloon times of 72 versus 97 minutes. Major adverse cardiovascular and cerebrovascular event rates were not statistically different between the U-IR versus U-DR groups (8% versus 12%, respectively, P=0.99). In comparison with the U-IR group, delaying reperfusion in the U-DR group did not affect 30-day mean infarct size measured as a percentage of LV mass (15±12% versus 13±11%, U-IR versus U-DR, P=0.53). Conclusions: We report that LV unloading using the Impella CP device with a 30-minute delay before reperfusion is feasible within a relatively short time period in anterior STEMI. The DTU-STEMI pilot trial did not identify prohibitive safety signals that would preclude proceeding to a larger pivotal study of LV unloading before reperfusion. An appropriately powered pivotal trial comparing LV unloading before reperfusion to the current standard of care is required. Clinical Trial Registration: URL: https://www.clinicaltrials. gov. Unique identifier: NCT03000270.
Contrasting evolutionary histories in Neotropical birds: Divergence across an environmental barrier in South America

Avian diversity in the Neotropics has been traditionally attributed to the effect of vicariant forces promoting speciation in allopatry. Recent studies have shown that phylogeographical patterns shared among codistributed species cannot be explained by a single vicariant event, as species responses to a common barrier depend on the biological attributes of each taxon. The open vegetation corridor (OVC) isolates Amazonia and the Andean forests from the Atlantic Forest, creating a notorious pattern of avian taxa that are disjunctly codistributed in these forests. Here, we studied and compared the evolutionary histories of Ramphotrigon megacephalum and Pipraeidea melanonota, two passerines with allopatric populations east and west of the OVC that represent different subspecies. These species differ in their biological attributes: R. megacephalum is a sedentary, forest specialist mostly confined to bamboo understorey, whereas P. melanonota is a seasonal migrant and generalist species that ranges in a variety of closed and semi‐open environments. We performed genetic and genomic analyses, complemented with the study of coloration and behavioural differentiation, to assess population divergence across the OVC. We found that the evolutionary histories of both R. megacephalum and P. melanonota have been shaped by this environmental barrier. However, these species responded in different and asynchronous manners to the establishment of the OVC and to past connections between the currently isolated South American forests, which can be mostly explained by their distinct ecologies and dispersal abilities. Our results support the fact that the biological attributes of species can make their evolutionary histories idiosyncratic.
Quercetin induces G2 phase arrest and apoptosis with the activation of p53 in an E6 expression-independent manner in HPV-positive human cervical cancer-derived cells

Cervical cancer is the second most common cancer in women worldwide. Human papillomavirus (HPV) infection appears to be a necessary factor in the development of almost all cases (>95%) of cervical cancer. HPV E6 induces a change of control of p53 stabilization from Hdm2 to E6/E6AP in HPV-infected cells. It is well known that the LxxLL motif of cellular ubiquitin ligase E6AP binds to the pocket of E6 and causes a conformational change to enable E6 to bind p53 competently. In the ternary complex E6/E6AP/p53, p53 is polyubiquitinated by E6AP and subsequently degraded by a proteasome. Therefore, these cells are deficient in the processes regulated by p53, including apoptosis, damaged DNA repair, and the cell cycle. In the present study, it was demonstrated that quercetin induced G2 phase cell cycle arrest and apoptosis in both HeLa and SiHa cells, accompanied by an increase of p53 and its nuclear signal. It was also observed that quercetin increased the level of the p21 transcript and the pro-apoptotic Bax protein, which are two p53-downstream effectors. However, quercetin did not alter the expression of the HPV E6 protein in cervical cancer cells; therefore, the increase in p53 occurred in an E6 expression-independent manner. Furthermore, molecular docking demonstrated that quercetin binds stably in the central pocket of E6, the binding site of E6AP. These data suggest that quercetin increases the nuclear localization of p53 by interrupting E6/E6AP complex formation in cervical cancer cells.
Pilot Studies on Two Complementary Bath Products for Atopic Dermatitis Children: Pine-Tar and Tea

Background: Few standardized bath product clinical trials were performed for atopic dermatitis patients. Pine-tar and green tea extracts are plant-derived products that have been described as having anti-allergic effects which may reduce AD disease severity. Methods: The efficacy of two complementary bath products was studied and compared. Efficacy and acceptability of the bath products were measured by patient general acceptability of treatment (GAT: very good, good, fair or poor), disease severity (SCORAD: SCoring Atopic Dermatitis), quality of life (CDLQI: Children Dermatology Life Quality Index), and pertinent clinical parameters were measured before and after four weeks of treatment. Sample size calculations for further clinical trials were performed. In one group, nine AD patients were subjected to bathing with a pine-tar bath oil for 10–15 min daily for four weeks. In another group, 20 AD subjects bathed with a teabag containing green tea extracts for four weeks. Results: Significant improvements in clinical- and patient-orientated parameters were found in the pine-tar bathing group, but not the tea-bag bathing group. Both groups reported very good/good GAT on the studied products. Teabag bathing was considered not efficacious for further clinical trials. Conclusions: The pilot studies provided preliminary data on the efficacy of pine tar bath oil. We do not document a significant efficacy for bathing with tea extracts. Bathing with pine-tar is potentially a complementary topical treatment with good patient acceptance and adherence, but further evidence-based research for its recommendations is needed.
The Prediction of Simulation Performance as It Is Affected By Time

This study deals with performance prediction in the business simulation. It is different from other studies in that it examines the relationship between performance and its predictor variables as that relationship changes over time. It presumes that the relative performance of simulation teams and some of the variables that influence performance do not remain static over the course of the simulation. Its intentions are to explore how time influences simulation events in general and simulation performance prediction in particular and to examine how the relationships between performance and its antecedents change over time.
NLRP3 inflammasome contributes to neurovascular unit damage in stroke

Abstract Recently, a wealth of information has emerged connecting the activation of the NLRP3 (NOD-like receptor family pyrin domain-containing 3) inflammasome to stroke pathogenesis, although the exact influence of the NLRP3 inflammasome on stroke is still in the stage of preliminary study and is awaiting further confirmation. In this paper, we will review the structure, assembly and activation of the NLRP3 inflammasome and its expression in the neurovascular units and will speculate on its possible roles in neurovascular injury post-stroke. Evidence on this topic suggests that targeting NLRP3-mediated inflammation at multiple levels may provide a new therapeutic strategy to prevent the deterioration of neurovascular units after stroke. However, many aspects of the biological link between the NLRP3 inflammasome and stroke remain ill-defined or even completely unknown. As fresh insights come to light regarding the NLRP3 inflammasome, the opportunities to develop new therapeutic strategies for stroke patients are expected to improve accordingly.
Resistin—Can it be a new early marker for prognosis in patients who survive after a cardiac arrest? A pilot study

Aim The aim of our study was to evaluate the potential role of resistin in estimating the 30 days prognosis in patients with hypoxic-ischemic organ injury who survived after a cardiac arrest (CA). Materials and methods The study included 40 patients resuscitated after a non-traumatic out-of-hospital CA admitted in Emergency Department (ED). All patients were followed for 30 days after CA or until death. Clinical data on admission were recorded. Blood samples were collected on admission in ED (0-time interval), and at 6, 12, 24, 48- and 72-hours following resuscitation. Serum concentrations of resistin, S100B and neuron specific enolase (NSE) were measured. Several predictive scores for the mortality at 30 days were created with logistic regressions. Results At each time interval, median serum levels of resistin and S100 B were significantly higher in non-survivors compared to survivors. For NSE, plasma levels were significantly lower in survivors as compared to non-survivors at 48 and 72 hours, respectively. Accurate predictive scores for 30-days mortality were the ones which included the values of resistin and S100B measured at 12 hours after admittance [AUC 0.938 (0.813–0.989), sensitivity 85.71% (67.3%– 96%), specificity 91.67% (61.5%’99.8%), p<0.001], which included the values of all three markers measured at 12 hours after admittance [AUC 0.955 (0.839–0.995), sensitivity 82.14% (63.1%’93.9%), specificity 100.00% (73.5%’100.0%), p<0.001] and the that included the values of resistin and S-100B at 6 hours together with serum lactate on admission [AUC = 0.994 (0.901–1.0), sensitivity 96.4% (81.7%’99.9%), specificity 100.00% (73.5%’100.0%), p<0.001]. Conclusion In our study, serum levels of resistin or a combination of resistin with S-100B or resistin with S-100B and lactate, were highly predictive for 30 days mortality in resuscitated patients after CA. Further studies on large number of patients are needed to confirm our data.
Serum Metabolic Profiling Identified a Distinct Metabolic Signature in Bladder Cancer Smokers: A Key Metabolic Enzyme Associated with Patient Survival

Background: The current system to predict the outcome of smokers with bladder cancer is insufficient due to complex genomic and transcriptomic heterogeneities. This study aims to identify serum metabolite-associated genes related to survival in this population. Methods: We performed LC/MS-based targeted metabolomic analysis for >300 metabolites in serum obtained from two independent cohorts of bladder cancer never smokers, smokers, healthy smokers, and healthy never smokers. A subset of differential metabolites was validated using Biocrates absoluteIDQ p180 Kit. Genes associated with differential metabolites were integrated with a publicly available cohort of The Cancer Genome Atlas (TCGA) to obtain an intersecting signature specific for bladder cancer smokers. Results: Forty metabolites (FDR < 0.25) were identified to be differential between bladder cancer never smokers and smokers. Increased abundance of amino acids (tyrosine, phenylalanine, proline, serine, valine, isoleucine, glycine, and asparagine) and taurine were observed in bladder cancer smokers. Integration of differential metabolomic gene signature and transcriptomics data from TCGA cohort revealed an intersection of 17 genes that showed significant correlation with patient survival in bladder cancer smokers. Importantly, catechol-O-methyltransferase, iodotyrosine deiodinase, and tubulin tyrosine ligase showed a significant association with patient survival in publicly available bladder cancer smoker datasets and did not have any clinical association in never smokers. Conclusions: Serum metabolic profiling of bladder cancer smokers revealed dysregulated amino acid metabolism. It provides a distinct gene signature that shows a prognostic value in predicting bladder cancer smoker survival. Impact: Serum metabolic signature–derived genes act as a predictive tool for studying the bladder cancer progression in smokers.
Exploring physical activity and sedentary behaviour: perspectives of individuals with osteoarthritis and knee arthroplasty

Abstract Purpose: To explore the understanding of physical activity and sedentary behaviour, including barriers and health influences in people with osteoarthritis and knee arthroplasty. Methods: Eight participants with knee osteoarthritis and 14 participants with total knee arthroplasty were recruited to five focus groups. Interpretive description was used with thematic analysis of data. Results: Three primary themes arose: (1) continuum of activity; (2) barriers to increasing physical activity and barriers to reducing sedentary behavior, and (3) knowledge gap. While participants were generally familiar with the concepts of physical activity and sedentary behaviour, they were not aware of health risks associated with high levels of sedentary time and did not consider substituting standing and light walking for activities typically done in sitting. Participants reported that extrinsic barriers (e.g., related to social and cultural contexts or the physical environment) influenced sedentary behaviour more than intrinsic factors. Conclusions: Patients would benefit from clinicians providing education about risks associated with sedentary behaviour and strategies to reduce and/or break up sitting time. Future research should continue to explore personal as well as societal, environmental, political, and economic influences on sedentary behaviour and physical activity to promote behaviour change. Implications for rehabilitation People with osteoarthritis and total knee arthroplasty are not aware of health risks associated with high levels of sedentary behaviour. This cohort tends to think about increasing moderate-to-vigorous physical activity levels (versus increasing light activity) when asked to consider ways to reduce sedentary behaviour. Social and environmental factors strongly influence sedentary behaviour. Clinicians need to be aware of the pervasive nature of sedentary behaviour and provide knowledge and strategies to change peoples’ sitting habits. Addressing intrinsic factors (e.g., related to comorbidities, ageing, and personal preferences) with education and the use of existing behaviour change techniques may enable increased physical activity levels.
PET imaging of microglia by targeting macrophage colony-stimulating factor 1 receptor (CSF1R)

Significance [11C]CPPC [5-cyano-N-(4-(4-[11C]methylpiperazin-1-yl)-2-(piperidin-1-yl)phenyl)furan-2-carboxamide] is a PET radiotracer specific for CSF1R, a microglia-specific marker. This compound can be used as a noninvasive tool for imaging of reactive microglia, disease-associated microglia and their contribution to neuroinflammation in vivo. Neuroinflammation is posited to be an underlying pathogenic feature of a wide variety of neuropsychiatric disorders. [11C]CPPC may also be used to study specifically the immune environment of malignancies of the central nervous system and to monitor potential adverse neuroinflammatory effects of immunotherapy for peripheral malignancies. This PET agent will be valuable in the development of new therapeutics for neuroinflammation, particularly those targeting CSF1R, not only by providing a noninvasive, repeatable readout in patients but also by enabling measurement of drug target engagement. While neuroinflammation is an evolving concept and the cells involved and their functions are being defined, microglia are understood to be a key cellular mediator of brain injury and repair. The ability to measure microglial activity specifically and noninvasively would be a boon to the study of neuroinflammation, which is involved in a wide variety of neuropsychiatric disorders including traumatic brain injury, demyelinating disease, Alzheimer’s disease (AD), and Parkinson’s disease, among others. We have developed [11C]CPPC [5-cyano-N-(4-(4-[11C]methylpiperazin-1-yl)-2-(piperidin-1-yl)phenyl)furan-2-carboxamide], a positron-emitting, high-affinity ligand that is specific for the macrophage colony-stimulating factor 1 receptor (CSF1R), the expression of which is essentially restricted to microglia within brain. [11C]CPPC demonstrates high and specific brain uptake in a murine and nonhuman primate lipopolysaccharide model of neuroinflammation. It also shows specific and elevated uptake in a murine model of AD, experimental allergic encephalomyelitis murine model of demyelination and in postmortem brain tissue of patients with AD. Radiation dosimetry in mice indicated [11C]CPPC to be safe for future human studies. [11C]CPPC can be synthesized in sufficient radiochemical yield, purity, and specific radioactivity and possesses binding specificity in relevant models that indicate potential for human PET imaging of CSF1R and the microglial component of neuroinflammation.
An Exploration of How Individuals with an Ostomy Communicatively Manage Uncertainty

ABSTRACT Individuals with an ostomy (a surgical diversion of part of the digestive tract through the abdomen) face a variety of uncertainties, due to the chronic and anatomy-altering nature of living with an ostomy, as well as the perceived stigma attached to having one. However, little is known about how these individuals negotiate uncertainty, and more specifically, how they manage the information they receive and disclose in the uncertainty management process. Thus, through 21 semi-structured interviews of individuals with an ostomy and the use of Uncertainty Management Theory as a theoretical framework, the current study found individuals with an ostomy attempted to negotiate uncertainty by managing information received and disclosed and by adapting to chronic uncertainty. This investigation recommends practical applications for medical professionals, supportive others, patients with an ostomy, as well as future surgical candidates to help manage uncertainty.
Navigational bronchoscopy at a community hospital: clinical and economic outcomes.

Aim To evaluate the clinical and financial impact of introducing electromagnetic navigation bronchoscopy (ENB) at a community center. Methods This retrospective, single-arm, single-center study evaluated 90 consecutive patients who had undergone ENB in 2012. Radial probe endobronchial ultrasound was used to localize the lesion after initial ENB. ENB-aided diagnoses, follow-up procedures and treatments, and adverse events were collected through 2 years. Results ENB was conducted for lung biopsy (86 patients), fiducial placement (five), and/or dye marking (two). ENB-aided diagnostic yield was 82.6% (71/86), including 36 malignant and 35 nonmalignant cases. NSCLC was stage I-II in 84.6%. There were four false negatives. Sensitivity and negative predictive value were 90.0 and 88.6%. Pneumothorax occurred in 6/90 (5/6 with chest tube) and minor bleeding in four. The downstream revenue of new ENB cases was US$363,654. Conclusion ENB introduction provided high diagnostic yield, early-stage diagnosis, acceptable safety, and was financially justified.
Consensus on the Rational Use of Antithrombotics in Veterinary Critical Care (CURATIVE): Domain 4—Refining and monitoring antithrombotic therapies

OBJECTIVES To systematically review the evidence for therapeutic monitoring of antithrombotic drugs in small animals, develop guidelines regarding antithrombotic monitoring, and identify knowledge gaps in the field. DESIGN First, a standardized, systematic literature review was conducted to address predefined PICO (Population/Patient, Intervention, Control, Outcome) questions, with categorization of relevant articles according to level of evidence and quality. Preliminary guidelines were developed by PICO worksheet authors and the domain chair. Thereafter, a Delphi-style survey was used to develop consensus on guidelines regarding therapeutic monitoring of antithrombotics in dogs and cats. SETTING Academic and referral veterinary medical centers. RESULTS PICO questions regarding the utility of therapeutic monitoring were developed for 6 different antithrombotic drugs or drug classes, including aspirin, clopidogrel, warfarin, unfractionated heparin, the low molecular weight heparins, and rivaroxaban, The majority of the literature pertaining to therapeutic monitoring of antithrombotic drugs was either performed in experimental animal models of disease or involved studies of drug pharmacokinetics and pharmacodynamics in healthy laboratory animals. There was a paucity of high level of evidence studies directly addressing the PICO questions, which limited the strength of recommendations that could be provided. The final guidelines recommend that therapeutic monitoring should be performed when using warfarin or unfractionated heparin in dogs and cats at risk of thrombosis. There is insufficient evidence to make strong recommendations for therapeutic monitoring of aspirin or low molecular weight heparin in dogs and cats at this time. CONCLUSIONS As in other CURATIVE domains, significant knowledge gaps were highlighted, indicating the need for substantial additional research in this field. Ongoing investigation of the role of therapeutic monitoring of antithrombotic therapies will undoubtedly facilitate improved outcomes for dogs and cats at risk of thrombosis.
Treating obesity in patients with cardiovascular disease: the pharmacotherapeutic options

ABSTRACT Introduction: Obesity is a growing health problem that has numerous comorbidities, including cardiovascular disease (CVD). The multi-disciplinary treatment of obesity now includes the use of pharmacotherapy. When treating patients with obesity and CVD, certain medications may be more appropriate than others. Areas covered: Herein, the authors review the most commonly used FDA approved medications for the treatment of obesity, describing their mechanism of action, and the efficacy and safety of the medications as seen in recent studies, particularly in patients with CVD. Expert opinion: In the population of patients with obesity and CVD, the medications orlistat, lorcaserin and liraglutide are considered the most appropriate options for their treatment, in terms of safety. Sympathomimetic medications, such as phentermine, should be avoided in this group. The recent CAMELLIA-TIMI 61 trial supports the safety of lorcaserin in patients with CVD. Until there are more studies, it is reasonable to extrapolate the findings of the LEADER trial, which found improved CV outcomes in subjects with type 2 diabetes taking liraglutide, to the population of nondiabetic patients being treated for obesity. Further cardiovascular outcomes trials (CVOT) are needed to assess the safety of other pharmacotherapeutic options for weight loss.