Miracle-dz/UniFAR-FTUs huggingface dataset:
Protein-mediated viral latency is a novel mechanism for Merkel cell polyomavirus persistence

Significance Viral latency is required for long-term persistence and allows viruses to evade host immune surveillance. We find that Merkel cell polyomavirus (MCV), a life-long human infection that can cause Merkel cell carcinoma, persists as a nonreplicating, silent infection owing to the continuous cellular turnover of its replication protein. Adverse cellular conditions, such as nutrient starvation, inhibit networks controlling MCV replication protein turnover and signal the virus to spread to uninfected cells or to a new host. This study describes a viral latency mechanism based on phosphorylation-regulated viral replication protein stability that may underlie chronic viral infections for some small genome DNA and RNA viruses. Viral latency, in which a virus genome does not replicate independently of the host cell genome and produces no infectious particles, is required for long-term virus persistence. There is no known latency mechanism for chronic small DNA virus infections. Merkel cell polyomavirus (MCV) causes an aggressive skin cancer after prolonged infection and requires an active large T (LT) phosphoprotein helicase to replicate. We show that evolutionarily conserved MCV LT phosphorylation sites are constitutively recognized by cellular Fbw7, βTrCP, and Skp2 Skp-F-box-cullin (SCF) E3 ubiquitin ligases, which degrade and suppress steady-state LT protein levels. Knockdown of each of these E3 ligases enhances LT stability and promotes MCV genome replication. Mutations at two of these phosphoreceptor sites [serine (S)220 and S239] in the full viral genome increase LT levels and promote MCV virion production and transmission, which can be neutralized with anti-capsid antibody. Virus activation is not mediated by viral gene transactivation, given that these mutations do not increase late gene transcription in the absence of genome replication. Mechanistic target of rapamycin inhibition by either nutrient starvation or use of an active site inhibitor reduces Skp2 levels and stabilizes LT, leading to enhanced MCV replication and transmission. MCV can sense stresses in its intracellular environment, such as nutrient loss, through SCF E3 ligase activities, and responds by initiating active viral transmission. Protein-mediated viral latency through cellular SCF E3 ligase targeting of viral replication proteins is a unique form of latency that may promote chronic viral persistence for some small DNA and RNA viruses.
Evaluation of two methods for quality improvement in intensive care: Facilitated incident monitoring and retrospective medical chart review*

ObjectiveQuality assurance techniques applied within the healthcare industry have been widely used and are intended to improve patient outcomes. Two methods that have been utilized are incident reporting and medical chart review (MCR). The objectives for this study were to evaluate facilitated incident monitoring (FIM) and MCR in the intensive care setting. DesignCross-sectional comparison of prospective FIM and retrospective MCR. SettingTertiary, 12-bed, closed intensive care unit (ICU) in Australia providing adult and pediatric intensive care to surgical, medical, trauma, and retrieval patients. PatientsPatients present or admitted to the ICU during the 2-month study period. Measurement and Main ResultsDuring the study period, there were 176 admissions involving 164 patients. A total of 100 FIM reports, of which 70 related to care provided by the ICU team, identified 221 incidents. There were 30 FIM reports that described adverse events, of which only one related to ICU team care. Potential of harm was estimated to be minimal in 49% and significant in 51%; 84% of incidents were considered preventable. Important contextual information was provided, including evidence for the importance of system factors. MCR identified 132 adverse events involving 48% of charts, and 47 related to ICU team care. Common adverse events included nosocomial infections, aspiration, neurologic compromise, respiratory arrest, delayed diagnosis, and treatment. Twenty percent of adverse events were considered preventable, and in 41%, there was evidence of system causation. ConclusionFIM provided more contextual information about incidents and identified a larger number and higher proportion of preventable problems than MCR, but FIM identified few iatrogenic infections, problems with pain management, or problems leading to ICU admission. FIM is easily incorporated into the clinical routine. This study suggests that incident monitoring may be more useful for identifying quality problems, and it could be supplemented by selective audits and focused MCR to detect problems not reported well by FIM.
Estimation of global visual impairment due to uncorrected refractive error.

The paper by Resnikoff et al.1 on the global magnitude of visual impairment caused by uncorrected refractive error published in the Bulletin of the World Health Organization in January 2008 does not refer to our previous publication2 on the same topic in BMC Medicine that precedes their paper by about two years and is readily available in the public domain. The reason for this is unclear as our paper clearly shows up in a PubMed® search for both “blindness” and “visual impairment”. In addition, the global estimates of blindness and visual impairment due to uncorrected refractive error made in our paper are know to the blindness community as they were presented at the World Ophthalmology Congress at Sao Paulo in February 2006. It is therefore surprising that Resnikoff et al. did not follow the usual norm of referring to previously published relevant literature. While there are differences in the inclusion criteria for studies in our paper and that of Resnikoff et al., with our paper using stricter criteria leading to fewer qualifying studies, and there were differences in the estimates of blindness and visual impairment due to uncorrected refractive error in the two papers, these should not be reasons for not referring to previously published work.
Role-Modeling and Medical Error Disclosure: A National Survey of Trainees

Purpose To measure trainees’ exposure to negative and positive role-modeling for responding to medical errors and to examine the association between that exposure and trainees’ attitudes and behaviors regarding error disclosure. Method Between May 2011 and June 2012, 435 residents at two large academic medical centers and 1,187 medical students from seven U.S. medical schools received anonymous, electronic questionnaires. The questionnaire asked respondents about (1) experiences with errors, (2) training for responding to errors, (3) behaviors related to error disclosure, (4) exposure to role-modeling for responding to errors, and (5) attitudes regarding disclosure. Using multivariate regression, the authors analyzed whether frequency of exposure to negative and positive role-modeling independently predicted two primary outcomes: (1) attitudes regarding disclosure and (2) nontransparent behavior in response to a harmful error. Results The response rate was 55% (884/1,622). Training on how to respond to errors had the largest independent, positive effect on attitudes (standardized effect estimate, 0.32, P < .001); negative role-modeling had the largest independent, negative effect (standardized effect estimate, −0.26, P < .001). Positive role-modeling had a positive effect on attitudes (standardized effect estimate, 0.26, P < .001). Exposure to negative role-modeling was independently associated with an increased likelihood of trainees’ nontransparent behavior in response to an error (OR 1.37, 95% CI 1.15–1.64; P < .001). Conclusions Exposure to role-modeling predicts trainees’ attitudes and behavior regarding the disclosure of harmful errors. Negative role models may be a significant impediment to disclosure among trainees.
THE USE OF NEAR INFRARED REFLECTANCE SPECTROMETRY FOR CHARACTERIZATION OF BROWN ALGAL TISSUE 1

Measuring qualitative traits of plant tissue is important to understand how plants respond to environmental change and biotic interactions. Near infrared reflectance spectrometry (NIRS) is a cost‐, time‐, and sample‐effective method of measuring chemical components in organic samples commonly used in the agricultural and pharmaceutical industries. To assess the applicability of NIRS to measure the ecologically important tissue traits of carbon, nitrogen, and phlorotannins (secondary metabolites) in brown algae, we developed NIRS calibration models for these constituents in dried Sargassum flavicans (F. K. Mertens) C. Agardh tissue. We then tested if the developed NIRS models could detect changes in the tissue composition of S. flavicans induced by experimental manipulation of temperature and nutrient availability. To develop the NIRS models, we used partial least squares regression to determine the statistical relationship between trait values determined in laboratory assays and the NIRS spectral data of S. flavicans calibration samples. Models with high predictive power were developed for all three constituents that successfully detected changes in carbon, nitrogen, and phlorotannin content in the experimentally manipulated S. flavicans tissue. Phlorotannin content in S. flavicans was inversely related to nitrogen availability, and nitrogen, temperature, and tissue age interacted to significantly affect phlorotannin content, demonstrating the importance of studies that investigate these three variables simultaneously. Given the speed of analysis, accuracy, small tissue requirements, and ability to measure multiple traits simultaneously without consuming the sample tissue, NIRS is a valuable alternative to traditional methods for determining algal tissue traits, especially in studies where tissue is limited.
Enhanced saliva-mediated bacterial aggregation and decreased bacterial adhesion in caries-resistant versus caries-susceptible individuals

A study of saliva-mediated aggregation and adhesion has been carried out in a group of caries-resistant (CR) and caries-susceptible (CS) individuals. The submandibular saliva of the CS group had a much greater potency, as determined by dilution, in promoting adherence to hydroxyapatite beads than did the saliva of CR group. In contrast, the CR group demonstrated a twofold enhancement of saliva-mediated aggregation compared with the CS group. These observations support the hypothesis that saliva-mediated aggregation and adherence are important factors in caries resistance.
TRUSTe: an online privacy seal program

Oligomeric organo metallic resins which are divalent metal acylates of the formula: X M D M X, wherein each X is an acyloxy ligand of a monobasic acid containing at least 7 carbon atoms; D is a diacyloxy radical (ligand) of a dibasic acid containing at least 6 carbon atoms; and M is a divalent metal atom other than calcium are provided. These novel oligomeric resins are particularly suitable as coating compositions and when they contain oxidizable divalent metals are especially rapid drying.
HMGB1: Endogenous Danger Signaling

While foreign pathogens and their products have long been known to activate the innate immune system, the recent recognition of a group of endogenous molecules that serve a similar function has provided a framework for understanding the overlap between the inflammatory responses activated by pathogens and injury. These endogenous molecules, termed alarmins, are normal cell constituents that can be released into the extracellular milieu during states of cellular stress or damage and subsequently activate the immune system. One nuclear protein, High mobility group box-1 (HMGB1), has received particular attention as fulfilling the functions of an alarmin by being involved in both infectious and non-infectious inflammatory conditions. Once released, HMGB1 signals through various receptors to activate immune cells involved in the immune process. Although initial studies demonstrated HMGB1 as a late mediator of sepsis, recent findings indicate HMGB1 to have an important role in models of non-infectious inflammation, such as autoimmunity, cancer, trauma, and ischemia reperfusion injury. Furthermore, in contrast to its pro-inflammatory functions, there is evidence that HMGB1 also has restorative effects leading to tissue repair and regeneration. The complex functions of HMGB1 as an archetypical alarmin are outlined here to review our current understanding of a molecule that holds the potential for treatment in many important human conditions.
The Src Homology 2 Domain of Rin1 Mediates Its Binding to the Epidermal Growth Factor Receptor and Regulates Receptor Endocytosis*

Activated epidermal growth factor receptors (EGFRs) recruit intracellular proteins that mediate receptor signaling and endocytic trafficking. Rin1, a multifunctional protein, has been shown to regulate EGFR internalization (1). Here we show that EGF stimulation induces a specific, rapid, and transient membrane recruitment of Rin1 and that recruitment is dependent on the Src homology 2 (SH2) domain of Rin1. Immunoprecipitation of EGFR is accompanied by co-immunoprecipitation of Rin1 in a time- and ligand-dependent manner. Association of Rin1 and specifically the SH2 domain of Rin1 with the EGFR was dependent on tyrosine phosphorylation of the intracellular domain of the EGFR. The recruitment of Rin1, observed by light microscopy, indicated that although initially cytosolic, Rin1 was recruited to both plasma membrane and endosomes following EGF addition. Moreover, the expression of the SH2 domain of Rin1 substantially impaired the internalization of EGF without affecting internalization of transferrin. Finally, we found that Rin1 co-immunoprecipitated with a number of tyrosine kinase receptors but not with cargo endocytic receptors. These results indicate that Rin1 provides a link via its SH2 domain between activated tyrosine kinase receptors and the endocytic pathway through the recruitment and activation of Rab5a.
The Combined Effects of Exercise, Diet, and a Multi-Ingredient Dietary Supplement on Body Composition and Adipokine Changes in Overweight Adults

ABSTRACT Background: Very few weight and fat loss supplements undergo finished-product research to examine efficacy. The purpose of this study was to determine the effects of an 8-week diet and exercise program on body composition, hip and waist girth, and adipokines and evaluate whether a dietary supplement containing raspberry ketone, capsaicin, caffeine, garlic, and Citrus aurantium enhanced outcomes. Methods: Overweight men and women completed this randomized, placebo-controlled, double-blind study. Participants consumed 4 capsules/d of supplement (EXP; n = 18) or placebo (PLA; n = 18). Participants underwent 8 weeks of daily supplementation, calorie restriction (500 kcal < RMR [resting metabolic rate] × 1.2), and supervised progressive exercise training 3 times a week. Body composition, girth, and adipokines were assessed at baseline and postintervention (T1 and T2). Results: Significant decreases in weight (−2.6 ± 0.57 kg, p < 0.001), fat mass (−1.8 ± 0.20 kg; p < 0.001), and percentage body fat (−3.7% ± 0.29%, p < 0.001) and a significant increase in lean body mass (LBM; 1.5 ± 0.26 kg; p < 0.001) were seen from T1 to T2 in both groups. For men, only those in the EXP group increased LBM from T1 to T2 (1.3 ± 0.38 kg; p < 0.05). Hip girth was also reduced, with the women in the EXP group (−10.7 ± 2.15 cm, p < 0.001) having a greater reduction. There was a time by group interaction, with significant decreases in leptin (p < 0.001) and significant increases in adiponectin (p < 0.05) in the EXP group. Conclusions: Significant improvements in adipokines and leptin support the utility of exercise, diet, and fat loss for impacting inflammatory biomarkers. The improvement in adiponectin with EXP may suggest a unique health mechanism.
Manufacturing competence: a key to successful supplier integration

Extensive involvement of suppliers in new product development and manufacturing development has often been associated with superior performance. Some authors have also alleged that companies need comprehensive internal competencies, or absorptive capacity, in order to fully benefit from external expertise. This paper analyses this relationship on an operational level in manufacturing companies. Based on a large-scale survey it is shown that companies with greater internal manufacturing competencies gain significantly from supplier involvement in terms of most performance indicators, whereas those with lesser internal competencies have little to gain from such external cooperation.
Discrete dynamic Bayesian network analysis of fMRI data

We examine the efficacy of using discrete Dynamic Bayesian Networks (dDBNs), a data‐driven modeling technique employed in machine learning, to identify functional correlations among neuroanatomical regions of interest. Unlike many neuroimaging analysis techniques, this method is not limited by linear and/or Gaussian noise assumptions. It achieves this by modeling the time series of neuroanatomical regions as discrete, as opposed to continuous, random variables with multinomial distributions. We demonstrated this method using an fMRI dataset collected from healthy and demented elderly subjects (Buckner, et al., 2000 : J Cogn Neurosci 12:24‐34) and identify correlates based on a diagnosis of dementia. The results are validated in three ways. First, the elicited correlates are shown to be robust over leave‐one‐out cross‐validation and, via a Fourier bootstrapping method, that they were not likely due to random chance. Second, the dDBNs identified correlates that would be expected given the experimental paradigm. Third, the dDBN's ability to predict dementia is competitive with two commonly employed machine‐learning classifiers: the support vector machine and the Gaussian naïve Bayesian network. We also verify that the dDBN selects correlates based on non‐linear criteria. Finally, we provide a brief analysis of the correlates elicited from Buckner et al.'s data that suggests that demented elderly subjects have reduced involvement of entorhinal and occipital cortex and greater involvement of the parietal lobe and amygdala in brain activity compared with healthy elderly (as measured via functional correlations among BOLD measurements). Limitations and extensions to the dDBN method are discussed. Hum Brain Mapp, 2009. © 2007 Wiley‐Liss, Inc.
Oxidative stress change by systemic corticosteroid treatment among patients having active graves ophthalmopathy.

OBJECTIVES To measure the 8-hydroxy-2'-deoxyguanosine (8-OHdG) level in patients having active Graves ophthalmopathy (GO) and to compare this oxidative stress biomarker and the clinical evolution of patients after systemic corticosteroid treatment. METHODS In 8 euthyroid patients having active GO, we determined the 8-OHdG levels in urine before, during, and after intensive corticosteroid therapy. Clinical activity and ophthalmopathy index scores were assessed. Nine age- and sex-matched healthy volunteers served as control subjects. RESULTS The mean 8-OHdG level was statistically significantly increased in patients having active GO compared with that of controls (17.47 vs 5.97 ng/mg of creatinine, P < .001). During and after maximal systemic corticosteroid treatment, patients had statistically significantly lower mean 8-OHdG levels (7.19 and 10.18 ng/mg of creatinine, respectively) compared with the mean level before treatment. These changes were accompanied by decreases in clinical activity and ophthalmopathy index scores. The urinary 8-OHdG levels were subsequently elevated in 2 patients having recurrent active GO when corticosteroid therapy was tapered or withdrawn. CONCLUSIONS Oxidative stress may have a role in the pathogenesis of GO. Urinary 8-OHdG level can be used not only as a noninvasive biomarker of oxidative stress in patients having GO but also as an objective and quantitative parameter in the follow-up of patients during immunosuppressive treatment.
Autologous 111In‐labelled platelet sequestration studies in patients with primary immune thrombocytopenia (ITP) prior to splenectomy: a report from the United Kingdom ITP Registry

While splenectomy is an effective therapy for primary immune thrombocytopenia (ITP), possible complications and observed non‐complete response (CR) in one‐third of patients demonstrate the need for further research into potential pre‐surgical predictors of outcomes. Past investigations into platelet sequestration studies, a hypothesized predictive test, have adopted heterogeneous methods and varied widely with regard to power. By studying patients with primary ITP who underwent autologous 111In‐labelled platelet sequestration studies at Barts and The London NHS Trust between 1994 and 2008, we evaluated the effectiveness of sequestration site in predicting short, medium, and long‐term CR (platelet count >100 × 109/l) to splenectomy through multivariate (gender, age at splenectomy, and mean platelet lifespan) logistic regression modelling. In total, 256 patients with primary ITP underwent scans; 91 (35·5%) proceeded to splenectomy. Logistic regression revealed significant adjusted odds ratios for CR of 7·47 (95% confidence interval [CI], 1·89–29·43) at 1–3 months post‐splenectomy, 4·85 (95% CI, 1·04–22·54) at 6–12 months post‐splenectomy, and 5·39 (95% CI, 1·34–21·65) at last follow‐up (median: 3·8 years [range: 0·5–13·1 years]) in patients with purely or predominantly splenic versus mixed or hepatic sequestration. These findings demonstrate the utility of autologous 111In‐labelled platelet sequestration studies as an adjunct predictive instrument prior to splenectomy.
Partners' experiences of the postdischarge period after day surgery--a qualitative study.

AIMS AND OBJECTIVES Day surgery shifts the responsibility of care from the hospital to patients and their families. This study explored how partners of day surgery patients experienced their role after patient discharge. BACKGROUND Many surgical procedures formerly requiring inpatient care are now carried out on a day surgery basis, shifting responsibility of care to patients and their partners/relatives. Little is known about how partners of day surgery patients manage this responsibility. DESIGN Qualitative descriptive. METHODS Individual semi-structured interviews with 11 partners of day surgery patients who had undergone shoulder surgery. Systematic text condensation was used to analyse data. RESULTS The following aspects were identified: the first is 'It's all about being there for the patient by taking care of the patient's needs and by mobilising one's network,' referring to the provision of reassurance, helping with activities of daily living, facilitating information, being on the alert for adverse events and taking an average 1-4 days off work. The second is 'Contributing to society as a partner,' referring to partners' sense of citizenship resulting from being carers. Finally, prior experiences of hospitalisation and illness appeared to impinge upon partners' ways of taking on the responsibility of care. CONCLUSION Partners readily accepted their role as carers. This is essential for the day surgery concept to succeed. RELEVANCE TO CLINICAL PRACTICE In the light of the continuing expansion of day surgery and the ensuing transfer of care to patients and their relatives, it is important for healthcare professionals to assess relatives' capability to care for day surgery patients.