Miracle-dz/UniFAR-FTUs huggingface dataset:
Prevention of Postoperative Venous Thrombosis: A Randomized Trial Comparing Unfractionated Heparin with Low Molecular Weight Heparin in Patients Undergoing Total Hip Replacement

Summary A double blind randomized trial comparing subcutaneous enoxaparin (40 mg once daily) with standard unfractionated calcium heparin administered at a dose of 5,000 units every 8 hours in patients undergoing elective hip replacement has been performed. Treatment regimens began 12 hours preoperatively with enoxaparin, 2 hours preoperatively with standard unfractionated calcium heparin, and were continued for 15 days or until discharge. Venography was performed in all patients. Two hundred thirty-seven patients were included in the study: 113 received unfractionated heparin and 124 received enoxaparin. The incidence of proximal deep vein thrombosis was reduced from 18.5% in the unfractionated heparin group to 7.5% in the enoxaparin group (p = 0.014), and the incidence of total deep vein thrombosis was similarly reduced from 25% to 12.5% (p = 0.03). There were two major bleeding episodes and one minor bleed in the enoxaparin group compared to two minor bleeds in the unfractionated heparin group. Patients who received enoxaparin required fewer red blood cell transfusions and had a significantly higher hemoglobin on postoperative days 3 and 4. Thus prophylaxis with enoxaparin, 40 mg once daily, is simple, safe and more effective than standard low dose unfractionated heparin in preventing deep vein thrombosis in patients undergoing elective hip replacement.
Redesign of EdD and PhD Educational Leadership Programs

Over the past three decades, numerous calls have been issued from professional associations, government entities, researchers, and university faculty and administrators to strengthen the preparation of U.S. educational leadership programs. Survey responses were compared for educational leadership doctoral programs that have been redesigned versus those that have not. The results suggest that in spite of substantial numbers of EdD and PhD programs reporting redesigns, few changes have been made to align with emerging research or best practice. The only substantive change is in the use of a cohort-based design. Implications for future redesign efforts are discussed.
Examination of Neural Systems Sub-Serving Facebook “Addiction”

Because addictive behaviors typically result from violated homeostasis of the impulsive (amygdala-striatal) and inhibitory (prefrontal cortex) brain systems, this study examined whether these systems sub-serve a specific case of technology-related addiction, namely Facebook “addiction. ” Using a go/no-go paradigm in functional MRI settings, the study examined how these brain systems in 20 Facebook users (M age = 20.3 yr., SD = 1.3, range = 18–23) who completed a Facebook addiction questionnaire, responded to Facebook and less potent (traffic sign) stimuli. The findings indicated that at least at the examined levels of addiction-like symptoms, technology-related “addictions” share some neural features with substance and gambling addictions, but more importantly they also differ from such addictions in their brain etiology and possibly pathogenesis, as related to abnormal functioning of the inhibitory-control brain system.
Are Insights Gained from NOD Mice Sufficient to Guide Clinical Translation?

Abstract: Despite decades of research using various animal models for type 1 diabetes, we are still struggling to define the initiating autoantigens, the precise mechanisms of β cell destruction, and suitable immune‐based interventions to prevent or treat human diabetes. Animal models, such as the non‐obese diabetic (NOD) mouse and the biobreeding (BB) rat, develop immune‐mediated diseases with features resembling type 1 diabetes in humans. Although these animal models of autoimmune diabetes have proved to be valuable tools to study certain aspects of the disease process, they have also led to misconceptions and erroneous extrapolations, as well as false expectations with regard to the efficacy of immunotherapy. It is therefore time to ask ourselves whether we are making major strategic mistakes when employing rodent models for the study of type 1 diabetes. This review will describe where rodent models have provided us with proper guidance and where they have misled us, concluding that each model only offers partial information with undefined clinical value. Therefore, a more critical attitude and repetition of crucial observations in different model settings will be necessary in the future. I will argue that animal models have limited but evident value when it comes to teaching us about type 1 diabetes in humans, and we can take advantage of this value more efficiently.
Octreotide Inhibits Choroidal Neovascularization in Rats

Aims: Octreotide exhibits anti-angiogenic activity in animal models of retinopathy of prematurity and in clinical cases of proliferative diabetic retinopathy. In this study, we tested the applicability of using octreotide for inhibiting experimental choroidal neovascularization (CNV) in rats. Methods: Of 15 adult rats used, 3 served as non-laser-treated controls. CNV was induced in the right eye of the remaining 12 rats by laser photocoagulation. These 12 rats were divided into two groups (n = 6 each) which were retrobulbarly injected with octreotide (50 μg/kg) or phosphate-buffered saline (PBS) (0.15 ml) immediately and on day 3 after the first injection. Fluorescein angiography and quantitative analysis of the retinal pigment epithelium (RPE)-choroidal flat mounts were performed 14 days after the operation to evaluate the changes in the CNV lesions. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) was used to compare the changes shown by the octreotide-, PBS-, and non-laser-treated rats (n = 3 each) with regard to mRNA levels of the vascular endothelial growth factor (VEGF) and insulin-like growth factor (IGF)-1 in the RPE-choroidal complex. Results: Octreotide treatment significantly inhibited fluorescein leakage and the extent of neovascularization as was observed in the flat mounts of choroidal tissue derived from the rats with induced CNV. The VEGF and IGF-1 mRNA levels were reduced following treatment with octreotide. Conclusion: The retrobulbar administration of octreotide may be an effective new therapeutic strategy for CNV.
The Splicing History of an mRNA Affects Its Level of Translation and Sensitivity to Cleavage by the Virion Host Shutoff Endonuclease during Herpes Simplex Virus Infections

ABSTRACT During lytic herpes simplex virus (HSV) infections, the virion host shutoff (Vhs) (UL41) endoribonuclease degrades many cellular and viral mRNAs. In uninfected cells, spliced mRNAs emerge into the cytoplasm bound by exon junction complexes (EJCs) and are translated several times more efficiently than unspliced mRNAs that have the same sequence but lack EJCs. Notably, most cellular mRNAs are spliced, whereas most HSV mRNAs are not. To examine the effect of splicing on gene expression during HSV infection, cells were transfected with plasmids harboring an unspliced renilla luciferase (RLuc) reporter mRNA or RLuc constructs with introns near the 5′ or 3′ end of the gene. After splicing of intron-containing transcripts, all three RLuc mRNAs had the same primary sequence. Upon infection in the presence of actinomycin D, spliced mRNAs were much less sensitive to degradation by copies of Vhs from infecting virions than were unspliced mRNAs. During productive infections (in the absence of drugs), RLuc was expressed at substantially higher levels from spliced than from unspliced mRNAs. Interestingly, the stimulatory effect of splicing on RLuc expression was significantly greater in infected than in uninfected cells. The translational stimulatory effect of an intron during HSV-1 infections could be replicated by artificially tethering various EJC components to an unspliced RLuc transcript. Thus, the splicing history of an mRNA, and the consequent presence or absence of EJCs, affects its level of translation and sensitivity to Vhs cleavage during lytic HSV infections. IMPORTANCE Most mammalian mRNAs are spliced. In contrast, of the more than 80 mRNAs harbored by herpes simplex virus 1 (HSV-1), only 5 are spliced. In addition, synthesis of the immediate early protein ICP27 causes partial inhibition of pre-mRNA splicing, with the resultant accumulation of both spliced and unspliced versions of some mRNAs in the cytoplasm. A common perception is that HSV-1 infection necessarily inhibits the expression of spliced mRNAs. In contrast, this study demonstrates two instances in which pre-mRNA splicing actually enhances the synthesis of proteins from mRNAs during HSV-1 infections. Specifically, splicing stabilized an mRNA against degradation by copies of the Vhs endoribonuclease from infecting virions and greatly enhanced the amount of protein synthesized from spliced mRNAs at late times after infection. The data suggest that splicing, and the resultant presence of exon junction complexes on an mRNA, may play an important role in gene expression during HSV-1 infections.
The ROCO Kinase QkgA Is Necessary for Proliferation Inhibition by Autocrine Signals in Dictyostelium discoideum

ABSTRACT AprA and CfaD are secreted proteins that function as autocrine signals to inhibit cell proliferation in Dictyostelium discoideum. Cells lacking AprA or CfaD proliferate rapidly, and adding AprA or CfaD to cells slows proliferation. Cells lacking the ROCO kinase QkgA proliferate rapidly, with a doubling time 83% of that of the wild type, and overexpression of a QkgA-green fluorescent protein (GFP) fusion protein slows cell proliferation. We found that qkgA− cells accumulate normal levels of extracellular AprA and CfaD. Exogenous AprA or CfaD does not slow the proliferation of cells lacking qkgA, and expression of QkgA-GFP in qkgA− cells rescues this insensitivity. Like cells lacking AprA or CfaD, cells lacking QkgA tend to be multinucleate, accumulate nuclei rapidly, and show a mass and protein accumulation per nucleus like those of the wild type, suggesting that QkgA negatively regulates proliferation but not growth. Despite their rapid proliferation, cells lacking AprA, CfaD, or QkgA expand as a colony on bacteria less rapidly than the wild type. Unlike AprA and CfaD, QkgA does not affect spore viability following multicellular development. Together, these results indicate that QkgA is necessary for proliferation inhibition by AprA and CfaD, that QkgA mediates some but not all of the effects of AprA and CfaD, and that QkgA may function downstream of these proteins in a signal transduction pathway regulating proliferation.
Rituximab Failed to Improve Nephrotic Syndrome in Renal Transplant Patients With Recurrent Focal Segmental Glomerulosclerosis

Focal segmental glomerulosclerosis (FSGS) recurs in 30% of patients with FSGS receiving a first renal transplant and in over 80% of patients receiving a second transplant after a recurrence. Recurrence often leads to graft failure. The pathogenesis remains unknown and may involve a circulating permeability factor that initiates injury to the glomerular capillary. There are anecdotal reports of pediatric patients with posttransplant lymphoproliferative disorder (PTLD) and recurrent FSGS who have had remission of proteinuria after treatment with rituximab. These observations have prompted speculation that B cells may play a role in the pathogenesis of recurrent FSGS. We report four consecutive adult patients with early recurrent FSGS refractory or dependent on plasmapheresis who received rituximab (total dose 2000–4200 mg). None of the patients treated with rituximab achieved remission in proteinuria, and one patient experienced early graft loss. In these four adult renal transplant patients with recurrent FSGS, rituximab failed to diminish proteinuria.
The Process and Consequences of Institutionalizing an Elder

This qualitative study was conducted to examine the decision-making process and its immediate consequences forfamily members who placed an elderly loved one in a long-term care facility. To explore issues related to the placement process, in-depth interviews were conducted with 7 individuals who had recently (6 weeks or less) placed an older relative. Content analyses of the interviews were conducted, and several common themes related to the decision-making process and outcomes emerged. Most of the subjects hadprovided personal care for their elderly relative, so placing their loved one in a nursing home often conflicted with their view of themselves as an ideal caregiver During the process of making the decision, althoughfamily members were given advice and suggestions by health care professionals, this input was viewed as inadequate or even detrimental. Ultimately, subjects described making the decision to place an elderly relative in a long-term care facility as a singular process involving "I" rather than "we. " The positive and negative role of friends emerged as an important influence during and after the placement process. The informal validation of the decision to place by peers was the one interaction that family members identified as helpful during this process.
Assessment of oxidative stress in serum by d-ROMs test

Abstract Assessment of oxidative stress is an important but technically challenging procedure in medical and biological research. The reactive oxygen metabolites (d-ROMs) test is a simple assay marketed for analyzing the total amount of hydroperoxides in serum via the Fenton's reaction. Earlier reports have raised a suspicion that a part of the signal detected in the assay comes from sources other than metabolites generated by oxidative stress. The aim of this study was to identify which serum components interfere with the d-ROMs signal. By application of sodium azide, ethylenediaminetetraacetic acid, sodium dodecylsulphate, varying temperature, and spiking endogenous substances we demonstrate that in the case of mammalian sera the assay determines ceruloplasmin (CP) activity with potential interferences from hydroperoxides, iron level, thiols, and albumin. In sera of avian species hydroperoxides contribute more to the test outcome, but the CP part is insensitive to inhibition by azide. In conclusion, this assay has deficiencies in terms of detecting realistic concentrations of hydroperoxides, is mostly measuring CP and is also interfered with other serum components, making it very difficult to interpret in most biological systems.
Framing Terrorism : The News Media, the Government and the Public

Preface Introduction 1. Framing Terrorism, Pippa Norris, Montague Kern and Marion Just I. Generating Terrorist Frames 2. Terrorism, Censorship and the 1st Amendment: In Search of Policy Guidelines, Doris A. Graber 3. Clausewitz in the age of CNN: Rethinking the Military-Media Relationship, Robin Brown 4. Framing the Israeli-Palestinian conflict, Tamar Liebes and Anat First 5. Paramilitaries and the Press in Northern Ireland, Tim Cooke II. Comparing Terrorism Frames 6. Framing the US Embassy Bombings in African and US Newspapers, Todd M. Schaefer 7. Framing of the Afghanistan War by CNN and Al-Jazeera TV, Amy E. Jasperson and Mansour O. El-Kikhia 8. Framing the Muslim-Americans Before and After 9/11, Brigitte L. Nacos and Oscar Torres-Reyna 9. Framing World Opinion in the Elite Press, Frank Louis Rusciano III. The Public's Response 10. Explaining 9/11, Michael W. Traugott and Ted Brader 11. Public Opinion Among Muslims and the West, Pippa Norris and Ronald Inglehart 12. Rally Round the Flag: The Dynamics of System Support, Paul Brewer, Sean Aday and Kimberley Gross 13. Fear and Terrorism: Psychological Reactions to 9/11, Leonie Huddy, Stanley Feldman, Gallya Lahav and Charles Taber Conclusions 14. The Lessons of Framing Terrorism, Pippa Norris, Montague Kern and Marion Just Select Bibliography
Disseminated Single Tumor Cells as Detected by Real-Time Quantitative Polymerase Chain Reaction Represent a Prognostic Factor in Patients Undergoing Surgery for Colorectal Cancer

ObjectiveTo evaluate the clinical relevance of real-time quantitative polymerase chain reaction (qPCR) detection of CEA and CK20 transcripts, as potentially related to tumor cell dissemination, in blood and peritoneal lavage from patients undergoing surgery for colorectal cancer. Summary Background DataDissemination of single colorectal cancer cells in the peritoneal cavity, as well as in tumor drainage and peripheral blood vessels, might play a role in the metastasis process, thus affecting the clinical course. However, this phenomenon needs further elucidation. MethodsIn a prospective study the authors evaluated the potential of qPCR in the detection of CEA and/or CK20 transcripts in the peritoneal lavage fluid and in the peripheral and mesenteric venous blood of 39 patients undergoing curative resection for colorectal cancer. Peritoneal lavage and peripheral blood was sampled before and after tumor resection; mesenteric venous blood was sampled from the major tumor-draining vein immediately before clamping. After RNA extraction and reverse transcription, qPCR was performed using specific cDNA primers and probes for CEA and CK20. The dichotomous results from the qPCR were used as a predictor along with other covariates in Cox proportional hazard regression models of long-term outcome (disease-free survival and overall survival). ResultsOf 39 patients, 11 were positive. The median follow-up at analysis was 31 months for all patients. The dichotomous qPCR covariate was significant, with P = . 001 and . 0035 for disease-free survival and overall survival, respectively, in the proportional hazard regression models with only qPCR. In seven patients, disseminated colorectal cancer cells were found in the peritoneal lavage fluid but not in blood specimens; five of these patients (71%) had recurrence. ConclusionsThese data suggest that detection of mRNA coding for CEA and/or CK20 using qPCR has potential clinical utility as a prognostic marker and should be evaluated in larger clinical studies. Identification of patients at high risk for metastatic disease after curative resection of colorectal cancer might be improved by analyzing peritoneal lavage specimens in addition to blood samples. This is based on the observation that in more than half of qPCR-positive patients, disseminated colorectal cancer cells were detected in peritoneal lavage specimens but not in blood samples, and that 71% of them had recurrence.
Diagnosis of mild platelet function disorders. Reliability and usefulness of light transmission platelet aggregation and serotonin secretion assays

Light transmission platelet aggregation (PA), adapted to measure platelet secretion (PS), is the reference test for diagnosing platelet functional disorders (PFD). Problems with these assays include lack of standardisation, unknown reproducibility and lack of universally accepted diagnostic criteria. We addressed these issues in patients with inherited mucocutaneous bleeding (MCB). Normal and abnormal PA tests in 213 patients were reproducible in 93·3% and 90·4% of the cases, respectively. Mean intra‐subject coefficient of variation for PA with strong agonists were <9% and mean intra‐class correlation coefficient for weak agonists were >0·86 (P < 0·0001). Concomitant impaired PA with 10 μmol/l‐adrenaline and 4 μmol/l‐ADP was observed in 13·7% of the controls. This combination was not considered per se a criterion for PFD. PA with adrenaline ≥42% or irreversible aggregation with 4 μmol/l ADP had 93% and 95% Negative Predictive Value for diagnosing PFD, respectively. PA defects were consistently associated with abnormal PS. In contrast, 14·3% of patients with MCB had isolated PS. Thus, standardized PA/PS assays are highly reproducible and concordant in normal and patient populations. Normal PA with adrenaline and low ADP concentration robustly predict a normal PA. Simultaneous PA/PS assays enable the diagnosis of isolated PS defects. This study confirmed that hereditary PA–PS defects are highly prevalent.
Acute Hepatitis C Virus Structural Gene Sequences as Predictors of Persistent Viremia: Hypervariable Region 1 as a Decoy

ABSTRACT We hypothesized that hepatitis C virus (HCV) persistence is related to the sequence variability of putative envelope genes. This hypothesis was tested by characterizing quasispecies in specimens collected every six months from a cohort of acutely HCV-infected subjects (mean duration of specimen collection, 72 months after seroconversion). We evaluated 5 individuals who spontaneously cleared viremia and 10 individuals with persistent viremia by cloning 33 1-kb amplicons that spanned E1 and the 5′ half of E2, including hypervariable region 1 (HVR1). To assess the quasispecies complexity and to detect variants for sequencing, the first PCR-positive sample was examined by using a previously described method that combines heteroduplex analysis and analysis of single-stranded conformational polymorphisms. The ratio of nonsynonymous to synonymous substitutions (dN/dS ) within each sample was evaluated as an indicator of relative selective pressure. Amino acid sequences were analyzed for signature patterns, glycosylation signals, and charge. Quasispecies complexity was higher and E1dN/dS ratios (selective pressure) were lower in those with persistent viremia; the association with persistence was strengthened by the presence of a combination of both characteristics. In contrast, a trend toward higher HVR1dN/dS ratios was detected among those with persistent viremia. We did not detect any such association for factors that may affect complexity such as serum HCV RNA concentration. HVR1 had a lower positive charge in subjects with persistent viremia, although no consistent motifs were detected. Our data suggest that HCV persistence is associated with a complex quasispecies and immune response to HVR1.
Overexpression of a redox-regulated cutinase gene, MfCUT1, increases virulence of the brown rot pathogen Monilinia fructicola on Prunus spp.

A 4.5-kb genomic DNA containing a Monilinia fructicola cutinase gene, MfCUT1, and its flanking regions were isolated and characterized. Sequence analysis revealed that the genomic MfCUT1 carries a 63-bp intron and a promoter region with several transcription factor binding sites that may confer redox regulation of MfCUT1 expression. Redox regulation is indicated by the effect of antioxidants, shown previously to inhibit MfCUT1 gene expression in cutin-induced cultures, and in the present study, where H(2)O(2) enhanced MfCUT1 gene expression. A beta-glucuronidase (GUS) reporter gene (gusA) was fused to MfCUT1 under the control of the MfCUT1 promoter, and this construct was then used to generate an MfCUT1-GUS strain by Agrobacterium spp. -mediated transformation. The appearance of GUS activity in response to cutin and suppression of GUS activity by glucose in cutinase-inducing medium verified that the MfCUT1-GUS fusion protein was expressed correctly under the control of the MfCUT1 promoter. MfCUT1-GUS expression was detected following inoculation of peach and apple fruit, peach flower petals, and onion epidermis, and during brown rot symptom development on nectarine fruit at a relatively late stage of infection (24 h postinoculation). However, semiquantitative reverse-transcriptase polymerase chain reaction provided sensitive detection of MfCUT1 expression within 5 h of inoculation in both almond and peach petals. MfCUT1-GUS transformants expressed MfCUT1 transcripts at twice the level as the wild type and caused more severe symptoms on Prunus flower petals, consistent with MfCUT1 contributing to the virulence of M. fructicola.