Miracle-dz/UniFAR-FTUs huggingface dataset:
Predictors of Severe Thrombocytopenia Secondary to Peginterferon Alfa-2a Treatment in Subjects With Hepatitis C Virus Infection

In this study, we aim to identify patient characteristics that predict severe thrombocytopenia induced by peginterferon alfa-2a in hepatitis C virus–infected patients. Demographic, clinical, and genetic data collected from patients with chronic hepatitis C virus infection (n = 232; age ≥18 years) who received peginterferon alfa-2a following eltrombopag treatment. Predictors of severe thrombocytopenia (platelet count below 50 GI/L) were identified using a 2-step approach: First, univariate analysis, using &khgr;2 test for categorical variables and t test for continuous variables, was performed to identify possible predictors of severe thrombocytopenia (P < 0.05). Second, a logistic regression with backward stepwise selection was then performed using predictors identified in univariate analysis step to produce final model containing independent predictors at P < 0.05. Logistic model identified several predictors of severe thrombocytopenia. Increased spleen length and increased alkaline phosphatase levels increases the likelihood of severe thrombocytopenia. However, being Central/South Asian, increased neutrophils count and increased platelet baseline count decreases the probability of developing severe thrombocytopenia. In summary, we identified several patient characteristics that predict severe thrombocytopenia induced by peginterferon alfa-2a. Early selection of individuals with high risk of developing interferon-associated severe thrombocytopenia allows early intervention (such as eltrombopag treatment). Early intervention in turn minimizes the odds of developing severe thrombocytopenia and allows the continual of antiviral therapy before patient progress into liver decompensation.
The politics of bank ownership and currency policies in Central and Eastern Europe

ABSTRACT This paper argues that state-owned, private domestic, and foreign banks have different preferences for exchange rate policies. More specifically, I posit that governments will be less willing and able to maintain fixed exchange rate arrangements in closed banking systems dominated by government-owned banks than in globalized banking systems with a large presence of foreign banks. The article’s principal claim rests on the notion that ownership structure of the banking system empowers different types of banks, affects their interests, and shapes the responsiveness of government politicians to bank demands. The bank ownership types further influence the stability of the domestic monetary system and financial regulation that are of paramount importance in the determination of exchange rate regimes. An empirical investigation of data on exchange rate regimes for 25 Central and Eastern European countries provides strong support for the theory. The results are robust to alternative estimation techniques, instrumental variable analysis, and the inclusion of several economic and political variables.
Cellular cofactors affecting hepatitis C virus infection and replication

Recently identified hepatitis C virus (HCV) isolates that are infectious in cell culture provide a genetic system to evaluate the significance of virus–host interactions for HCV replication. We have completed a systematic RNAi screen wherein siRNAs were designed that target 62 host genes encoding proteins that physically interact with HCV RNA or proteins or belong to cellular pathways thought to modulate HCV infection. This includes 10 host proteins that we identify in this study to bind HCV NS5A. siRNAs that target 26 of these host genes alter infectious HCV production >3-fold. Included in this set of 26 were siRNAs that target Dicer, a principal component of the RNAi silencing pathway. Contrary to the hypothesis that RNAi is an antiviral pathway in mammals, as has been reported for subgenomic HCV replicons, siRNAs that target Dicer inhibited HCV replication. Furthermore, siRNAs that target several other components of the RNAi pathway also inhibit HCV replication. MicroRNA profiling of human liver, human hepatoma Huh-7.5 cells, and Huh-7.5 cells that harbor replicating HCV demonstrated that miR-122 is the predominant microRNA in each environment. miR-122 has been previously implicated in positively regulating the replication of HCV genotype 1 replicons. We find that 2′-O-methyl antisense oligonucleotide depletion of miR-122 also inhibits HCV genotype 2a replication and infectious virus production. Our data define 26 host genes that modulate HCV infection and indicate that the requirement for functional RNAi for HCV replication is dominant over any antiviral activity this pathway may exert against HCV.
Influence of Terminalia chebula on dermal wound healing in rats

The effects of topical administration of an alcohol extract of the leaves of an evergreen plant, Terminalia chebula, on the healing of rat dermal wounds, in vivo, was assessed. T. chebula treated wounds healed much faster as indicated by improved rates of contraction and a decreased period of epithelialization. Biochemical studies revealed a significant increase in total protein, DNA and collagen contents in the granulation tissues of treated wounds. The levels of hexosamine and uronic acid in these tissues, also increased up to day 8 post‐wounding. Reduced lipid peroxide levels in treated wounds, as well as ESR measurement of antioxidant activity by DPPH radical quenching, suggested that T. chebula possessed antioxidant activities. The tensile strength of tissues from extract‐treated incision wounds increased by about 40%. In addition, T. chebula possessed antimicrobial activity and was active largely against Staphylococcus aureus and Klebsiella. These results strongly document the beneficial effects of T. chebula in the acceleration of the healing process. Copyright © 2002 John Wiley & Sons, Ltd.
Comparative ultrastructural features of excitatory synapses in the visual and frontal cortices of the adult mouse and monkey

The excitatory glutamatergic synapse is the principal site of communication between cortical pyramidal neurons and their targets, a key locus of action of many drugs, and highly vulnerable to dysfunction and loss in neurodegenerative disease. A detailed knowledge of the structure of these synapses in distinct cortical areas and across species is a prerequisite for understanding the anatomical underpinnings of cortical specialization and, potentially, selective vulnerability in neurological disorders. We used serial electron microscopy to assess the ultrastructural features of excitatory (asymmetric) synapses in the layers 2–3 (L2–3) neuropil of visual (V1) and frontal (FC) cortices of the adult mouse and compared findings to those in the rhesus monkey (V1 and lateral prefrontal cortex [LPFC]). Analyses of multiple ultrastructural variables revealed four organizational features. First, the density of asymmetric synapses does not differ between frontal and visual cortices in either species, but is significantly higher in mouse than in monkey. Second, the structural properties of asymmetric synapses in mouse V1 and FC are nearly identical, by stark contrast to the significant differences seen between monkey V1 and LPFC. Third, while the structural features of postsynaptic entities in mouse and monkey V1 do not differ, the size of presynaptic boutons are significantly larger in monkey V1. Fourth, both presynaptic and postsynaptic entities are significantly smaller in the mouse FC than in the monkey LPFC. The diversity of synaptic ultrastructural features demonstrated here have broad implications for the nature and efficacy of glutamatergic signaling in distinct cortical areas within and across species.
Increase in severity of molar-incisor hypomineralization and its relationship with the colour of enamel opacity: a prospective cohort study.

BACKGROUND Predicting risk of posteruptive enamel breakdown (PEB) of molar-incisor hypomineralization (MIH) opacity is a difficult but important clinical task. Therefore, there is a need to evaluate these aspects through longitudinal studies. OBJECTIVE The aim of this longitudinal study was to analyse the relationship between colours of MIH opacity of children aged 6-12 (baseline) and other clinical and demographic variables involved in the increase in severity of MIH. MATERIALS AND METHODS A blinded prospective 18-month follow-up was conducted with 147 individuals presenting mild MIH. Tooth-based incidence of increase in severity of MIH (PEB or atypical restorations) was used as dependent measurement. Enamel opacities were recorded according to colour shades of white, yellow and brown, allowing assessment of susceptibility to structural loss over time, according to colour of MIH opacity. Poisson regression models were used to adjust the results for demographic and clinical variables. RESULTS Brown and yellow MIH opacities were at higher risk for PEB and atypical restorations than those of white ones, even after adjustment for clinical and demographic variables. CONCLUSION Teeth presenting mild MIH severity associated with yellow and brown enamel opacities were at high risk for increase in severity of MIH than lighter ones. This result could help clinicians determine a risk-based treatment for children with MIH.
Richard H. Thaler: A Nobel Prize for Behavioural Economics

ABSTRACT This paper provides an overview of Richard Thaler’s career and the contributions to behavioural economics that earned him the 2017 Nobel Memorial Prize in Economic Sciences. It focuses on his role in exposing and making sense of empirical anomalies in orthodox economics, his analysis of mental accounting, and his work with Cass Sunstein on the notion of libertarian paternalism and the ‘nudge’-based behavioural approach to economic policy. It then considers his contributions critically and explores how, unlike previous behavioural economics, Thaler succeeded in getting his new approach to behavioural economics accepted by mainstream economists.
Vaccinia Virus Virion Membrane Biogenesis Protein A11 Associates with Viral Membranes in a Manner That Requires the Expression of Another Membrane Biogenesis Protein, A6

ABSTRACT A group of vaccinia virus (VACV) proteins, including A11, L2, and A6, are required for biogenesis of the primary envelope of VACV, specifically, for the acquisition of viral membrane precursors. However, the interconnection among these proteins is unknown and, with the exception of L2, the connection of these proteins with membranes is also unknown. In this study, prompted by the findings that A6 coprecipitated A11 and that the cellular distribution of A11 was dramatically altered by repression of A6 expression, we studied the localization of A11 in cells by using immunofluorescence and cell fractionation analysis. A11 was found to associate with membranes and colocalize with virion membrane proteins in viral replication factories during normal VACV replication. A11 partitioned almost equally between the detergent and aqueous phases upon Triton X-114 phase separation, demonstrating an intrinsic affinity with lipids. However, in the absence of infection or VACV late protein synthesis, A11 did not associate with cellular membranes. Furthermore, when A6 expression was repressed, A11 did not colocalize with any viral membrane proteins or associate with membranes. In contrast, when virion envelope formation was blocked at a later step by repression of A14 expression or by rifampin treatment, A11 colocalized with virion membrane proteins in the factories. Altogether, our data showed that A11 associates with viral membranes during VACV replication, and this association requires A6 expression. This study provides a physical connection between A11 and viral membranes and suggests that A6 regulates A11 membrane association.
“Shift-and-Persist” Strategies

Some individuals, despite facing recurrent, severe adversities in life such as low socioeconomic status (SES), are nonetheless able to maintain good physical health. This article explores why these individuals deviate from the expected association of low SES and poor health and outlines a “shift-and-persist” model to explain the psychobiological mechanisms involved. This model proposes that, in the midst of adversity, some children find role models who teach them to trust others, better regulate their emotions, and focus on their futures. Over a lifetime, these low-SES children develop an approach to life that prioritizes shifting oneself (accepting stress for what it is and adapting the self through reappraisals) in combination with persisting (enduring life with strength by holding on to meaning and optimism). This combination of shift-and-persist strategies mitigates sympathetic-nervous-system and hypothalamic–pituitary–adrenocortical responses to the barrage of stressors that low-SES individuals confront. This tendency vectors individuals off the trajectory to chronic disease by forestalling pathogenic sequelae of stress reactivity, like insulin resistance, high blood pressure, and systemic inflammation. We outline evidence for the model and argue that efforts to identify resilience-promoting processes are important in this economic climate, given limited resources for improving the financial circumstances of disadvantaged individuals.
Corporate Sustainable Development. Revisiting the Relationship between Corporate Social Responsibility Dimensions

With rising stakeholder concerns over sustainable development, corporate social responsibility (CSR) has become key for the business community, moving the business model beyond financial performance to a new voluntary paradigm based on natural resource conservation, social welfare, stakeholder engagement and economic performance. This article aims to answer whether profitable business is compatible with balanced sustainability by investigating the relationship between the economic, social, environmental and governance performance for a sample of global firms. A canonical vine (C‐vine) copula is used for this purpose. Results show the existence of a fairly strong positive relationship between economic, social and environmental performance. The corporate governance dimension is shown to have a weak relationship with the rest of the CSR dimensions. Important policy implications are derived from these results. Copyright © 2017 John Wiley & Sons, Ltd and ERP Environment
Endoscopic hemoclipping for upper GI bleeding due to Mallory-Weiss syndrome.

BACKGROUND Endoscopic hemoclipping is known to be highly effective as hemostatic treatment for upper gastrointestinal bleeding. However, the efficacy and safety of hemoclipping for Mallory-Weiss syndrome (MWS) have not been reported. Thus, the aim of the present study was to assess prospectively the usefulness of endoscopic hemoclipping for MWS bleeding. METHODS This study was conducted from January 1994 to August 1999. Hemoclipping was performed when active bleeding (spurting, streaming or oozing), visible vessels or fresh adhesive clots were found on endoscopic examination. Patients who did not have any of these findings were conservatively treated. Follow-up endoscopy was performed within 24 hours, after 5 days and between 1 and 2 months after the procedure. RESULTS MWS was diagnosed in a total of 58 patients during the study. Hemoclipping was performed in 26 patients and was technically successful in all cases. The average number of hemoclips used was 2.8 +/- 1.6 (range 1 to 8). The number of hemoclips required for hemostasis depended on the nature of the bleeding. No complications, recurrent bleeding, or deaths resulted. Follow-up endoscopy showed no evidence of hemoclip-induced tissue injury and no impairment of Mallory-Weiss tears. CONCLUSION Endoscopic hemoclipping provided an effective and safe modality for obtaining hemostasis when bleeding is due to MWS.
Analysis of ecological thresholds in a temperate forest undergoing dieback

Positive feedbacks in drivers of degradation can cause threshold responses in natural ecosystems. Though threshold responses have received much attention in studies of aquatic ecosystems, they have been neglected in terrestrial systems, such as forests, where the long time-scales required for monitoring have impeded research. In this study we explored the role of positive feedbacks in a temperate forest that has been monitored for 50 years and is undergoing dieback, largely as a result of death of the canopy dominant species (Fagus sylvatica, beech). Statistical analyses showed strong non-linear losses in basal area for some plots, while others showed relatively gradual change. Beech seedling density was positively related to canopy openness, but a similar relationship was not observed for saplings, suggesting a feedback whereby mortality in areas with high canopy openness was elevated. We combined this observation with empirical data on size- and growth-mediated mortality of trees to produce an individual-based model of forest dynamics. We used this model to simulate changes in the structure of the forest over 100 years under scenarios with different juvenile and mature mortality probabilities, as well as a positive feedback between seedling and mature tree mortality. This model produced declines in forest basal area when critical juvenile and mature mortality probabilities were exceeded. Feedbacks in juvenile mortality caused a greater reduction in basal area relative to scenarios with no feedback. Non-linear, concave declines of basal area occurred only when mature tree mortality was 3–5 times higher than rates observed in the field. Our results indicate that the longevity of trees may help to buffer forests against environmental change and that the maintenance of old, large trees may aid the resilience of forest stands. In addition, our work suggests that dieback of forests may be avoidable providing pressures on mature and juvenile trees do not pass critical thresholds.
Preliminary results of an early vs delayed timing of surgery in the management of proximal femur fragility fractures.

INTRODUCTION The appropriate surgical timing for the treatment of proximal femur fractures is still debated. Advantages of a delayed surgery may be: stabilization of systemic diseases, decrease of the risk of perioperative mortality and morbidity. An early timing of surgery may allow: early mobilization, reduction of the risks of disability and hospital stays, early return to home of the patients. However, the effects on mortality are still discussed. PURPOSE The purpose of this study is to assess the influence of the surgical timing on clinical outcomes, complications, and mortality in a preliminary experience of the early management of these fractures vs the delayed surgery. METHODS A series of 176 patients was retrospectively evaluated. 132 patients were followed-up for one year after surgery. The evaluation was performed by the assessment of the comorbidities, preoperative wait for surgery, type of fracture and procedures, hospital stay, and functional outcomes: 33 patients were operated with an early timing, 99 with a delayed surgery. RESULTS The mean mortality rate was 18.2% in the early timing (6/33 patients), and 23.2% in the delayed timing (23/99 patients): no significant difference was recorded in the preliminary analysis. Postoperative complications were recorded in 28 patients (21.2%): 4 patients were operated within 48 hours (12.1%) and 24 after 48 hours (24.2%) with no substantial differences. The postoperative hospital stay showed no correlation with the timing of surgery, as no evidence was found on the functional recovery and postoperative disability. CONCLUSIONS No significant differences were found on the evaluated parameters in the two groups in the present preliminary study. A correlation between male sex and mortality, and male sex and postoperative complications was assessed. An enlargement of the study population is needed to surely clarify any effective differences, given the fact that recent studies seem to identify in the early treatment the better strategy to ensure the best recovery and the lower rate of mortality and complications.
Achieving Temporal Ambidexterity in New Ventures

Organizations face a common intertemporal choice problem, where actions suitable in the shortterm are different from those that work in the longterm. Building on the organizational ambidexterity theory, we argue that organizations can reconcile their short&#8208;term and long&#8208;term tensions, but this does necessitate managerial endeavours that orchestrate this reconciliation. We introduce the concept of temporal ambidexterity and define four intertemporal tensions involving an organization&#8217;s objectives, resources, markets, and uncertainty. We examine how firms can address these tensions successfully in the context of new ventures, and to do so we focus on three managerial capabilities of founder&#8208;CEOs: expertise breadth, external connectivity, and empowering leadership. Results from 243 new ventures in China suggest that temporal ambidexterity improves with these managerial capabilities, and more so for younger ventures. Our findings shed light on solutions and mechanisms by which intertemporal balance is fulfilled, particularly for new ventures in a dynamic environment.
A longitudinal study of the effects of lithium treatment on prefrontal and subgenual prefrontal gray matter volume in treatment-responsive bipolar disorder patients.

OBJECTIVE Recent molecular, preclinical, and preliminary clinical studies suggest that the therapeutic effects of mood stabilizers may be mediated by modulating expression of potent neurotrophic and neuroprotective factors having the potential to reverse impairments of cellular resilience, reductions in brain volume, and cell death or atrophy. Our main goal was to investigate the potential clinical significance of these findings in relation to bipolar disorder. METHOD The longitudinal effect of lithium on brain gray matter volume was investigated in well-characterized (DSM-IV criteria) bipolar depressed subjects (N = 28) at baseline (medication-free) and after lithium administration (4 weeks). Total brain gray matter, prefrontal gray matter, and left subgenual prefrontal gray matter volumes were determined using validated semiautomated segmentation and region of interest methodology. The study was conducted from November 1997 until April 2004 at Wayne State University School of Medicine, Detroit, Mich. RESULTS Significant increases in total brain gray matter volume in bipolar subjects were observed after 4 weeks of lithium administration (p = .0043). Moreover, regional analyses in the bipolar subjects revealed significant differences between responders (>50% decrease in Hamilton Depression Rating Scale total score) and nonresponders; only responders showed a significant increase in gray matter volume in the prefrontal cortex (p = .003) and an increase at trend level in the left subgenual prefrontal cortex volume (p = .0786). CONCLUSION The increase in gray matter volume in these areas, which various neuroimaging and postmortem neuropathology studies have implicated in the neuropathophysiology of bipolar disorder, suggests that the observed effects may be linked to clinical response. The findings also support the notion that future treatments that more directly target molecules in critical central nervous system pathways that regulate cellular plasticity hold promise as novel, improved, long-term treatments for mood disorders as well as some neurodegenerative conditions, such as Alzheimer's disease. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00870311.