Miracle-dz/UniFAR-FTUs huggingface dataset:
cis Elements and trans factors are both important in strain-specific regulation of the leukotoxin gene in Actinobacillus actinomycetemcomitans

Actinobacillus actinomycetemcomitans, the etiologic agent of localized juvenile periodontitis, produces a potent leukotoxin that kills human neutrophils. The production of leukotoxin RNA can vary more than 50-fold among isolates of A. actinomycetemcomitans, and strains expressing high levels of leukotoxin RNA are most often found at sites of periodontal disease. To assess the relative contributions of transcription factors and promoter sequences in setting the disparate levels of leukotoxin RNA found, we have undertaken classical cis/trans analyses. First, the leukotoxin promoter regions from moderately leukotoxic (Y4) and minimally leukotoxic (ATCC 33384) strains of A. actinomycetemcomitans were cloned, sequenced, and compared with the previously sequences leukotoxin promoter region of the high-producer strain JP2. The Y4 and ATCC 33384 promoter regions each contain a 528-bp segment that is absent from JP2. Interestingly, the analysis of various deletion constructs in A. actinomycetemcomitans indicated that Y4, despite the large insertion, initiates leukotoxin RNA synthesis at the same promoter as JP2 does. To perform cis/trans analyses, these three leukotoxin promoter regions were cloned into a plasmid upstream of the reporter gene beta-galactosidase. Each plasmid was transformed into JP2, Y4, and ATCC 33384, and the beta-galactosidase levels were determined. The results indicated that the sequences responsible for down-regulating leukotoxin RNA levels in Y4 relative to JP2 are found within the transcribed region of the Y4 leukotoxin operon. Importantly, in ATCC 33384, strain-specific trans factors and promoter sequence differences are equally significant in determining the lower levels of leukotoxin RNA. We hypothesize that either strain ATCC 33384 has a negative regulatory protein (which is missing or mutated in JP2/Y4) or that JP2 and Y4 carry an activator that is missing or mutated in ATCC 33384.
Prasugrel hydrochloride for the treatment of acute coronary syndromes

Introduction: P2Y12 receptor antagonists, by inhibiting platelet activation and subsequent aggregation, are critical to prevent ischemic event recurrence after an acute coronary syndrome (ACS). Prasugrel is a third-generation thienopyridine whose metabolites target the P2Y12 receptor. Compared with clopidogrel, prasugrel has a more potent, faster in onset, and more consistent P2Y12 receptor inhibition. Areas covered: This review describes prasugrel chemistry, pharmacokinetics, pharmacodynamics and clinical studies. In a Phase III randomized clopidogrel-controlled trial, prasugrel improved cardiovascular outcome (risk reduction of cardiovascular death, non-fatal heart attack and non-fatal stroke) at the cost of increased major and fatal bleeding complications. Prasugrel, in combination with aspirin, has been approved by European and American regulatory agencies for the prevention of atherothrombotic events in patients with ACS who undergo percutaneous coronary intervention (PCI). Expert opinion: Prasugrel is effective for managing ACS patients with planned PCI and it offers an alternative with potential benefits over clopidogrel. Prasugrel is currently challenged by ticagrelor, a P2Y12 receptor antagonist with different pharmacokinetic/pharmacodynamic properties. The superiority of one drug to the other cannot be reliably estimated from the current trials. Ongoing randomized and observational studies may help to provide valuable information on the safety and efficacy of these two drugs and their respective places with ACS patients.
Nodular Basal Cell Carcinoma Arising in a Split-Thickness Skin Graft of the Scalp

AbstractWe present the first known case of basal cell carcinoma arising in a split-thickness skin graft in the United States. The apparent low incidence of basal cell carcinoma in split-thickness skin graft attests to its unique environment and could possibly be attributed to the following: (1) the donor sites for split-thickness skin grafts are usually areas that are not subjected to heavy sun exposure; (2) individuals with skin grafts may not live as long on average, or their skin grafts may be subsequently excised with further reconstructive procedures; and (3) cases may be underreported. Because basal cell carcinomas have a fairly benign course, many patients either do not present to a physician or are not reported. This case shows that a split-thickness skin graft can have an adequate microenvironment for the development of basal cell carcinoma.
Potency and Resistance Analysis of Hepatitis C Virus NS5B Polymerase Inhibitor BMS-791325 on All Major Genotypes

ABSTRACT BMS-791325 is a hepatitis C virus (HCV) inhibitor binding to the thumb domain of the NS5B RNA-dependent RNA polymerase. BMS-791325 is well characterized in genotype 1 (GT1) and exhibits good inhibitory activity (50% effective concentration [EC50], <10 nM) against hybrid replicons containing patient NS5B sequences from GT3a, -4a, and -5a while potency against GT2 is significantly reduced (J. A. Lemm et al., Antimicrob. Agents Chemother. 58:3485–3495, 2014, doi:http://dx.doi.org/10.1128/AAC.02495-13). BMS-791325 potency against GT6a hybrid replicons is more variable, with two of three hybrid clones having EC50s similar to that for GT1 while a third patient clone was ∼10 times less susceptible to BMS-791325. To characterize the resistance profile of BMS-791325 beyond GT1, curing studies were performed across GT1a and -3a to -6a and demonstrated that GT1a has the highest resistance barrier versus BMS-791325 while GT6a has the lowest. Selection of GT3 to -6 NS5B chimeric replicon cells at different concentrations of BMS-791325 revealed substitutions in the thumb domain of NS5B at residues 494 and 495 that conferred different levels of resistance to BMS-791325 but remained susceptible to NS5A or NS3 protease inhibitors. In addition, we demonstrate that the reduced potency of BMS-791325 against one GT6a patient is due to an A494 polymorphism present in ∼21% of sequences in the European HCV database. The results from this report suggest that BMS-791325 is a candidate for combination treatment of HCV GT3 to -6 chronic infections, and the resistance profiles identified will provide useful information for future clinical development.
Differences in the implementation of diagnosis-related groups across clinical departments: a German hospital case study.

OBJECTIVE This article aims to examine the implementation process of diagnosis-related groups (DRGs) in the clinical departments of a German hospital group and to explain why some gain competitive advantage while others do not. STUDY SETTING To investigate this research question, we conducted a qualitative study based on primary data obtained in six clinical departments in a German hospital group between 2003 and 2005. STUDY DESIGN We chose the case study method in order to gain deep insights into the process dynamics of the implementation of DRGs in the six clinical departments. The dynamic capability approach is used as a theoretical foundation. Employing theory-driven categories we focused on idiosyncratic and common patterns of "successful coders" and "unsuccessful coders. " DATA COLLECTION To observe the implementation process of DRGs, we conducted 43 semistructured interviews with key persons, carried out direct observations of the monthly meetings of the DRG project group, and sampled written materials. PRINCIPAL FINDINGS "Successful coders" invest into change resources, demonstrate a high level of acceptance of innovations, and organize effective processes of coordination and learning. CONCLUSIONS All clinical departments only put an emphasis on the coding aspects of the DRGs. There is a lack of vision regarding the optimization of patient treatment processes and specialization. Physicians are the most important key actors, rather than the main barriers.
Fibrinogen/fibrin degradation products in acute aortic dissection.

BACKGROUND The elevated D-dimer value is one of the clues used to diagnose acute aortic dissection (AAD), but the rapid D-dimer assay is not used at all emergency hospitals. The fibrinogen/fibrin degradation products (FDP) value is also an indicator of enhanced fibrinolysis and may therefore be a useful marker in patients with AAD. In addition, the association between FDP values and partial thrombosis of the false lumen is not elucidated. PATIENTS The present study enrolled 50 patients (66.5±11.2 years of age; median, 66.5 years of age, male subjects comprised 60.0% of the series) with AAD who were admitted to the hospital between July 2005 and December 2007 and 57 patients with acute myocardial infarction (AMI; 70.8±10.4 years of age; median, 71.0 years of age, male subjects comprised 71.9% of the current series) served as a control group. RESULTS The FDP values (µg/mL) in patients with AAD were significantly higher than those of AMI patients (40.2±78.6; median, 14.7 vs. 5.2±9.8; median, 1.7, p<0.001). A receiver operating characteristic curves analysis showed that an elevated FDP level (2.05 µg/mL) was predictive of a diagnosis of AAD with a sensitivity and specificity of 98% and 54%, respectively. The FDP levels of patients (n=14) who had partial thrombosis of the false lumen were significantly higher than in discharged patients without a surgical repair (n=21) who had a patent or complete thrombosis of the false lumen (35.8±43.2; median, 18.8 vs. 14.0±21.3; median, 5.5, p=0.01). CONCLUSION The measurement of FDP may therefore be useful for the initial assessment of patients with suspected AAD and in the prediction of thrombotic status of the false lumen.
The Cross-Sectional Variation of Skewness Risk Premia

This paper estimates skewness risk premia on individual stocks using synthetic skew swaps and shows that there is a considerably large variation of monthly realized skewness risk premia across a representative set of portfolios which are sorted by skewness risk premium payoffs in the prior period. It then focuses on investigating the determinants of such cross-sectional variation and documents that consumption risk does not seem to be priced with respect to skewness risk premia. The market excess return and, especially, the market variance risk premium are shown to be key risk factors that drive the cross-sectional variation of skewness risk premium payoffs. The market variance risk premium factor is significantly priced with respect to skewness risk premia even if I allow for potential model misspecification. The success of the market variance risk premium factor can be potentially explained by the very different risk exposures of skewness risk premium-based portfolios to the risk proxied by the market variance risk premium. I further show that the higher the exposure of the skewness risk premium-based portfolio to such a risk, the larger skewness risk premium payoff is required in the cross section.
Endoscopic palliation of patients with biliary obstruction caused by nonresectable hilar cholangiocarcinoma: efficacy of self-expandable metallic Wallstents.

BACKGROUND The aim of this study was to evaluate the efficacy of an endoscopically inserted self-expandable metal stent for treatment of biliary obstruction caused by nonresectable hilar cholangiocarcinoma. METHODS Data on all patients with nonresectable hilar cholangiocarcinoma receiving self-expandable metal stents between January 1990 and April 2000 were retrospectively reviewed. Patients with pseudo Klatskin tumors (metastases in the liver hilum) and gallbladder carcinoma were excluded. Early complications (within 30 days of stent placement), early and late stent occlusion, stent patency, and biliary reintervention rates were recorded. RESULTS Fifty-two Wallstents were inserted in 36 patients, with 7, 13, and 16 having, respectively, Bismuth type I/II, III, and IV lesions. Insertion was successful in 35 of 36 (97%) patients. Complications occurred within the first 30 days after insertion in 5 patients (14%) but did not require biliary reintervention. Thirty-day mortality was 6% (2 deaths). There were 3 early (9%) and 8 late (23%) stent occlusions, bringing the total to 11 patients (31%) who required biliary reintervention after Wallstent insertion. Median Wallstent patency and patient survival were, respectively, 169 days (95% CI [154, 184]) and 147 days (95% CI [106, 188]), with no difference between patients with Bismuth I/II, III, IV type tumors. CONCLUSIONS Wallstent insertion is safe and feasible, and achieves successful palliation without the need for further biliary reintervention in the majority (69%) of patients with nonresectable hilar cholangiocarcinoma.
SELECTIVE EFFECTS OF LOMERIZINE, A NOVEL DIPHENYLMETHYLPIPERAZINE Ca2+ CHANNEL BLOCKER, ON CEREBRAL BLOOD FLOW IN RATS AND DOGS

1. In the present study we examined the effects of a new Ca2+ channel blocker (lomerizine), an antimigraine drug, on cerebral cortical blood flow (CBF) in anaesthetized rats (laser Doppler flowmetry) and on vertebral blood flow in anaesthetized beagle dogs (electromagnetic flowmeter).
From peer assessment towards collaborative learning

Peer assessment is one form of innovative assessment which aims to integrate learning and assessment. Peer assessment can also be seen as a special type of collaborative learning, where the task can be specified by using so called collaboration scripts. This implies the application of a more or less rigid schema (collaboration script) for structuring the task. Although peer assessment has positive effects on knowledge acquirement there is a lack of web-based collaborative peer assessment systems. Thus we have implemented a peer assessment application for review and discussion of artifacts. In our approach it is new that students use presentation recording tools to create personal presentations. It is possible to use these continuous documents for peer assessment. With this approach we lift restrictions to submit only static documents for peer review.
The Influence of Perceived Justice on Recovery Satisfaction in the Airline Industry

ABSTRACT This study examines the influence of perceived justice on customer satisfaction with service recovery and on the future behavioral intentions of customers in the airline industry. The study uses an exploratory research design that is quantitative in nature. Questionnaires were used to collect data, and structural equation modeling was used for hypothesis testing. The study revealed that the three dimensions of perceived justice, namely interactional, distributive and procedural justice, influence satisfaction with service recovery in the South African airline industry. However, only interactional and distributive justice had a positive influence on future behavioral intention.
Manduca sexta recognition and resistance among allopolyploid Nicotiana host plants

Allopolyploid speciation occurs instantly when the genomes of different species combine to produce self-fertile offspring and has played a central role in the evolution of higher plants, but its consequences for adaptive responses are unknown. We compare herbivore-recognition and -resistance responses of the diploid species and putative ancestral parent Nicotiana attenuata with those of the two derived allopolyploid species Nicotiana clevelandii and Nicotiana bigelovii. Manduca sexta larvae attack all three species, and in N. attenuata attack is recognized when larval oral secretions are introduced to wounds during feeding, resulting in a jasmonate burst, a systemic amplification of trypsin inhibitor accumulation, and a release of volatile organic compounds, which function as a coordinated defense response that slows caterpillar growth and increases the probability of their being attacked. Most aspects of this recognition response are retained with modifications in one allotetraploid (N. bigelovii) but lost in the other (N. clevelandii). Differences between diploid and tetraploid species were apparent in delays (maximum 1 and 0.5 h, respectively) in the jasmonate burst, the elicitation of trypsin inhibitors and release of volatile organic compounds, and the constitutive levels of nicotine, trypsin inhibitors, diterpene glycosides, rutin, and caffeoylputrescine in the leaves. Resistance to M. sexta larvae attack was most strongly associated with diterpene glycosides, which were higher in the diploid than in the two allotetraploid species. Because M. sexta elicitors differentially regulate a large proportion of the N. attenuata transcriptome, we propose that these species are suited for the study of the evolution of adaptive responses requiring trans-activation mechanisms.
Nomenclature of Cutaneous Vasculitis

To prepare a dermatologic addendum to the 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides (CHCC2012) to address vasculitides affecting the skin (D‐CHCC). The goal was to standardize the names and definitions for cutaneous vasculitis.
International Yield Curves and Currency Puzzles

The depreciation rate is often computed as the ratio of foreign and domestic pricing kernels. Using bond prices alone to estimate these kernels leads to currency puzzles: the inability of models to match violations of uncovered interest parity and the volatility of exchange rates. That happens because of the FX bond disconnect, the inability of bonds to span exchange rates. This view of the puzzles is distinct from market incompleteness. Incorporating exchange rates into estimation of yield curve models helps with resolving the puzzles. That approach also allows one to relate the cross-country differences between international yields to currency risk premiums.
Proliferation of weakly suppressive regulatory CD4+ T cells is associated with over‐active CD4+ T‐cell responses in HIV‐positive patients with mycobacterial immune restoration disease

The role of Treg in patients with late‐stage HIV disease, who commence combination antiretroviral therapy (cART) and develop pathogen‐specific immunopathology manifesting as immune restoration disease (IRD) remains unclear. We hypothesised that Treg could be defective in either numbers and/or function and therefore unable to ensure the physiological equilibrium of the immune system in patients with IRD. Phenotypic and functional CD4+ T‐cell subsets of eight late‐stage HIV patients with nadir CD4 count <50 cells/μL, who developed mycobacterial IRD upon commencing cART were compared with six therapy naive HIV+ patients (nadir CD4 count <50 cells/μL), who did not develop an IRD after cART. Mycobacterium‐avium‐specific CD4+ T cells from IRD patients produced high levels of IFN‐γ and IL‐2 compared with controls (p<0.001). Surprisingly, we found a significant expansion of CD127loFoxp3+CD25+ Treg in IRD patients and a higher ratio of Treg to effector/memory subsets (p<0.001). In vitro suppression assays demonstrated reduced functional capacity of suppressor cells and diminished IL‐10 secretion in IRD patients. Plasma levels of IL‐7 were increased in patients and, interestingly, exogenous IL‐7 and other cytokines strongly inhibited Treg suppression. These data suggest that despite substantial Treg expansion in IRD, their ability to induce suppression, and thereby downregulate aberrant immune responses, is compromised.
The role of financial development on foreign direct investment in asean-5 countries: Panel cointegration with cross-sectional dependency analysis

This paper investigates the impact of the financial development on foreign direct investment (FDI) inflows in ASEAN-5 countries over the period of 1980A±2013. The 5 countries included in this study are Malaysia, Thailand, Indonesia, Singapore and Philippines. In the model, financial development, consumer price index (CPI) and real gross domestic product (GDP) per capita are the independent variables. The stationarity of the variables is examined through both first- and second-generation unit root tests with the cross-sectional dependence among countries. The Pedroni and Westerlund cointegration tests results show the existence of long run relationship among the variables. Long term coefficients are estimated using Fully Modified Ordinary Least Square (FMOLS) model and it reveals that financial development has a nonlinear relation with FDI. When financial development passes the threshold point at above 70 point, it will benefit the FDI. Furthermore, the Panel Vector Error Correction Model (VECM) is applied to examine the causality relationship among the associated variables. The causality analysis confirms the presence of both long- term relationship and short term dynamic among the FDI, financial development, CPI and real GDP per capita.
Use of Pesticides and Its Impact on Health of Farmers in South India

Abstract The relationship between extent of pesticide use and signs and symptoms of illnesses due to exposure was assessed in a cross-sectional survey of 631 farmers (537 men and 94 women) in South India. Responses to questionnaires showed that 433 farmers (68.6%) sprayed pesticides themselves and were thus directly exposed. More than 75% used moderately or highly hazardous pesticides; 88% used no protection while handling pesticides. About 50% of sprayers mixed different brands. Retailers were the source of information about pesticides for 56%. The farmers reported excessive sweating (36.5%), burning/stinging/itching of eyes (35.7%), dry/sore throat (25.5%), and excessive salivation (14.1%), all more prevalent among sprayers. Among men, excessive sweating and eye and throat problems were significantly associated with exposure. There is a need to raise farmers' and authorities' awareness of the need to use protective gear when handling pesticides.
Access to Continuing Education for Critical Care Nurses in Rural or Remote Settings

&NA; Caring for the critically ill does not occur solely in large medical centers or urban areas. Nurses practicing in rural or remote settings practice as nurse generalists, caring for a wide range of patients, including those needing critical care. As a nurse generalist, the need for a wide variety of skill sets challenges nurses in rural areas to maintain current practice through continuing education across many content areas. They also may not come in contact with critically ill patients or emergent situations as often as their urban counterparts, which can make remaining comfortable with more advanced skills difficult. Because nurses working in rural or remote areas may care for critically ill patients less often, the need to remain vigilant in pursuit of continuing education is increased; however, access to continuing education can be problematic because of geographic isolation, difficulty getting time off from work, limited financial resources, and perceived lack of applicable topics. With advances in technology, critical care nurses working in rural areas have more options for continuing education, which is crucial for maintaining a skilled nursing workforce in rural health care facilities. This article addresses challenges critical care nurses working in remote or rural areas face in pursuing continuing education and provides information about available educational opportunities.