Miracle-dz/UniFAR-FTUs huggingface dataset:
Dukes stage B colorectal cancers analysed with array comparative genomic hybridisation

Introduction: The main aim was to investigate Dukes B cancer prognosis using array comparative genomic hybridisation (aCGH). The cancers were typed for microsatellite instability (MSI), APC loss of heterozygosity (LOH) and ploidy. A secondary aim was the selection, on the basis of aCGH results, of potential colorectal cancer genes using In Situ Hybridisation (ISH). Sporadic adenomas were also investigated with aCGH to investigate the timing of chromosomal instability in tumourigenesis. Methods: Dukes B cancers collected in Oxford, Leeds and Harrow were examined using aCGH based on a set of 3452 BAC clones at ~1Mb spacing. MSI was assessed using BAT26 and D5S346. D5S346 gave LOH at the APC gene locus. Ploidy was assessed using flow cytometry (FACS). From the aCGH data genes in regions of copy number gain were chosen for ISH analysis. Results: 79 Dukes B cancers (43 good outcome, 36 bad outcome on the basis of 5 year survival) were investigated with aCGH. The most commonly gained chromosomes across all cancers were 13, 20 and 7, and the most commonly lost were 22, 18 and 14. Comparing survival groups; chromosome 6 was more often lost in cancers associated with good outcome, chromosome 16 was more often gained in microsatellite stable cancers associated with good outcome, and chromosome 22 more often gained in microsatellite stable cancers associated with poor outcome. Chromosome 13 showed greater than single copy number change significantly more often in bad outcome cancers. Several new areas of small genomic gain and loss were detected. Four candidate genes were identified (CDX2, RHOA, FLT1 and ARHGEF1). None showed a relationship with outcome. Large scale chromosomal changes were found in 10 of14 sporadic adenomas. Conclusions: Array CGH did identify some difference between good and bad outcome Dukes B cancers. However on the basis of this data, the technique could not be used as a useful clinical tool to predict prognosis.
ACCELERATED GRAFT ARTERIOSCLEROSIS IN CARDIAC TRANSPLANTS

Background. A critical role for the terminal compo- nents of complement (C5b-C9) has been demonstrated previously in acute allograft rejection with the use of C6-deficient PVG congenic rat strains. The C6 deficiency prevents the formation of membrane attack complex (MAC) by C5b-C9. Hearts transplanted from PVG.1A (RT1 a ) rats are rejected acutely (7–9 days) by fully MHC-incompatible C6-sufficient PVG.1L (RT1 1 ) recipients, but they survive significantly longer in un- treated C6-deficient PVG.1L recipients (19 to > 60 days). Methods. To investigate the contribution of MAC to chronic rejection and accelerated graft arteriosclero- sis (AGA) in long-term cardiac allografts, hearts were transplanted heterotopically from PVG.1A donors to C6-sufficient and C6-deficient PVG.1L hosts that were treated with cyclosporine 15 mg/kg/day for 14 days after cardiac grafting. Alloantibody responses in hosts were measured by flow cytometry at 4, 8, 12, and 16 weeks after transplantation. Vigorously contracting grafts were removed at 60 days (n (cid:1) 5) and at 90–128 days (n (cid:1) 12) after surgery for morphological evaluation. Computerized planimetry measurements were made in complete cross-sections of grafts on all assess-able arteries larger than 16 microns in diameter. Results. The survival of most (six of seven) cardiac allografts in C6-deficient recipients was prolonged by cyclosporine treatment to greater than 90 days. In con-trast, 14 of 25 hearts that were transplanted to C6- sufficient recipients were rejected between 21 and 84 days with severe vascular injury. AGA, defined as smooth muscle cells forming a neointima inside the internal elastic lamina and luminal compromise, af- fected a greater percentage of arteries in C6-sufficient than in C6-deficient recipients. AGA developed earlier and more frequently in arteries of medium ( < 100 micron) diameter than those of large diameter in both C6-sufficient and C6-deficient recipients. Serial sections demonstrated the lesions in medium arteries to be located adjacent to the smooth muscle sphincters at the junction of arteriolar branches. Conclusions. These results demonstrate that MAC promotes the pathogenesis of AGA in long-term car- diac allografts. a and PVG.1L (RT1 1 ) rat strains were used in this study. The MHC phenotype of these congenic rats and the C6 levels in their sera were by flow cytometry and ELISA, All animals hu-mane in compliance with the Principles of Laboratory and the Guide for the Care and Use of Laboratory Animals Laboratory
Cerebral Blood Flow in Superficial Temporal Artery to Middle Cerebral Artery Anastomosis. In: Microsurgery for Cerebral Ische-

7. Gee W, Miller AL, Madden AE, Stephens HW and Whitehouse GE: Ocular Pneumoplethysmography in Carotid Occlusive Disease. In: Microsurgery for Cerebral Ischemia. S.J. Peerless and C.W. McCormick, eds, Springer-Verlag, New York, 1980, pp 106-109 8. Carney AL: Ocular Plethysmography and Suction Ophthalmodynamometry in the Diagnosis of Carotid Occlusive Disease. In: Microvascular Anastomosis for Cerebral Ischemia. J.M. Fein and O.H. Reichman, eds, Springer-Verlag, New York, 1978, pp 117131 9. Reichman OH: Estimation of Flow Through STA Bypass Graft. In: Microvascular Anastomosis for Cerebral Ischemia. J.M. Fein and
Perceived Risk of Emerging Recreational Drugs: Impact of Anecdotal and Statistical Evidence

This study investigated the relative impact of personal stories and base rate evidence on the perceived risk of using two emerging recreational drugs: kratom and Spice. A 3 × 2 × 2 mixed-methods design was employed. Four hundred fifty-three young adults were randomly assigned to read internet postings that presented either 1) base rate information depicting the frequency of adverse reactions to Spice and kratom; 2) base rate information plus four personal web-postings describing beneficial reactions to Spice and kratom; or 3) base rate information plus four personal web-postings describing adverse reactions to Spice and kratom. Respondents subsequently evaluated the risk of using both drugs. Anecdotal evidence (personal stories) outweighed the impact of base rate evidence only when the personal stories described adverse drug reactions. Effective risk communication will benefit from differential use of both base rate evidence and personal stories.
Rate of stimulation a¡ects schizophrenia-normal di¡erences on the N1 auditory-evoked potential

The present study examined how increasing the rate of steadystate stimulation a¡ects schizophrenia-normal di¡erences on the N1 auditory-evoked potential, an index of auditory integration. Dense-array EEG was recorded while schizophrenia and normal subjects heard 1 kHz tones amplitude modulated at 10, 20, 40, or 80Hz. Spectral power across frequency and time was calculated. The typically lowerN1amplitude in schizophrenia, observed at the 10Hz burst rate, increased to nearly equal that of normal individuals at 20Hz. Unlike normal subjects, schizophrenia subjects’ power at N1 failed to increase at the 40 and 80Hz burst rates. These results suggest steady-state stimuli, up to a point, provide the extra information needed for schizophrenia patients to more e⁄ciently integrate auditory information. NeuroReport 15:2713^2717 c 2004 LippincottWilliams &Wilkins.
A Cytopathic Effect-Based High-Throughput Screening Assay Identified Two Novel Compounds that Inhibit Dengue Infection: Streptovitacin A and Nagilactone C

Dengue is an emerging infectious disease and is spreading world-wide at exponential levels. Two billion people in over 100 countries are at risk for infection from one of the four serotypes of the dengue virus. Those infected with dengue may develop diseases such as dengue fever and dengue hemorrhagic fever (DHF) and of the 500,000 cases that progress to DHF each year, more than 22,000 will result in fatality. Discovering new antivirals to treat DHF is essential to reducing this disease burden. Here, we have developed a cytopathic effect-based high-throughput screen (HTS) to discover possible inhibitors of Dengue viral infection of hepatocytes in vitro. Dengue virus infection of hepatocytes induces massive cell death, "cytopathic effect (CPE)", which we converted into a screening assay whereby inhibitors of Dengue infection prevent cells from dying. In this assay, the viral induced CPE is quantitated by monitoring cellular ATP levels, which positively correlates with cellular viability. ATP in the cell culture will drive the oxidation of luciferin resulting in the emission of light that is quantitated using a luminometer. The assay is simple and highly reproducible yielding a screening window coefficient, Z-factor, of 0.78±0.12 between plates. The Z-factor is a statistical parameter commonly accepted as an assay quality assessment and is reported as a value 0 to 1 and anything over 0.5 is considered excellent quality. This assay is advantageous to current methodology as it simultaneously screens possible inhibitory compounds while controlling for any unwanted toxicity triggered by these drugs. Our initial HTS of a 288 small compound library yielded a total of eleven hits that prevented the CPE of dengue infection. Further evaluation with an immunofluorescence assay showed that two of these compounds, Streptovitacin A and Nagilactone C, are highly potent inhibitors of dengue infection. At effective inhibitory doses, they did not appear to be cytotoxic, and therefore both of these compounds are possible antivirals and could be used to elucidate various cellular mechanisms utilized during the dengue life cycle. The discovery of these two inhibitors demonstrates the efficacy of our newly developed assay and the public health significance of this project.
Mechanisms Underlying Ras-Induced Methuosis in Human Glioblastoma Cells

Methuosis is a unique form of non-apoptotic cell death that is characterized by dysfunction in the trafficking of clathrin-independent endosomes. This leads to extensive cellular vacuolization and ultimately death of the cell. Methuosis can be induced in glioblastoma cells by expression of constitutively activated H-Ras. This study identifies the signaling pathways that govern H-Ras-induced methuosis in human glioblastoma cells. Our studies establish that the small GTPases, Rac1 and Arf6, and the Arf6 GAP, GIT1, act as key downstream components of the signaling pathway underlying H-Ras-induced methuosis. Activated H-Ras-induced methuosis depends upon Rac1 activation and the consequent interaction of active Rac1 with GIT1 to inactivate Arf6 and prevent the recycling of the clathrin-independent endosomes back to the plasma membrane. Studies to test the effect of a closely related Ras GTPase, R-Ras, in glioblastoma cells reveal that it induces cellular vacuolation but does not lead to cell death. Expression of constitutively active R-Ras in glioblastoma cells induces cytoplasmic vacuolation dependent upon Rac1 activation and subsequent inactivation of Arf6. The latter might prevent recycling of vacuoles back to the plasma membrane. However, R-Ras-induced vacuoles do not expand progressively like H-Ras-induced vacuoles, and the cells do not undergo methuosis. H-Ras(G12V) expression in the cells leads to an increase in the levels of active Rab7. Vacuoles in cells expressing H-Ras(G12V) contain H-Ras(G12V) and Rab7(Q67L) on their membranes. These vacuoles fail to fuse with lysosomes. Interestingly, R-Ras(G38V) does not localize to vacuoles. Unlike the cells expressing H-Ras(G12V), cells expressing R-Ras(G38V) are not metabolically compromised. We postulate that though the expression of active R-Ras in glioblastoma cells induces cellular vacuolation, the induced vacuoles might be competent to fuse with the lysosomes, thus preventing methuosis. Further studies to identify the different signaling pathways underlying the effects of H-Ras and R-Ras on vesicular trafficking would help to identify key regulators of the initial steps that lead to methuosis. This might help identify potential therapeutic targets that can be manipulated to induce methuosis in cancers that are refractory to apoptosis.
Operational Topic IMPACT OF COMPARISON GROUP ON COHORT DOSE RESPONSE REGRESSION: AN EXAMPLE USING RISK ESTIMATION IN ATOMIC-BOMB SURVIVORS

Cohort-based dose-response analyses can be biased if based on a comparison group that is not comparable to the exposed persons with respect to uncontrolled factors related to disease incidence or mortality. When data exist over a range of doses including the very low dose region, internal regression standardized analyses based on the regression intercept derived from the exposed subcohort alone can provide risk estimates that are not subject to such comparison-group bias. In the Life Span Study cohort of atomic-bomb survivors, persons with dose estimates of zero comprise a broader geographic distribution than that of persons with non-zero dose estimates. Because there is geographic variation in mortality rates, the zero-dose persons might bias background rate estimates thereby affecting inference about radiation risk. This is illustrated using mortality due to all causes. Restricting the comparison group to certain geographically defined subcohorts resulted in as much as a 6% increase or 8% decrease in the risk estimate. This bias can be corrected using an SMRtype estimate in the regression model, allowing retention of the comparison group in the analysis if it is needed for stability or precision in estimating age, time, and sex effects. Consideration of heterogeneity in comparison groups is particularly important in dose-response studies focused on low doses at which the response may be comparable in magnitude to such
Clinical Trial of Measles and Rubella Combined Vaccine Produced by POLYVAC in Vietnam

A clinical trial of measles and rubella combined vaccine (MR: MRVAC) produced by POLYVAC was conducted in Vietnam in 2016. A total of 756 subjects were enrolled, and 504 were allocated to MRVAC and 252 to control MR vaccine groups. Paired sera were obtained in 733, and the number of subjects was 403 aged 1 - 2 years, 164 aged 2 - 18 years, and 166 aged 18 - 45 years. Antibodies against measles and rubella viruses were evaluated by EIA. Most subjects had been immunized with a single dose of Expanded Programme on Immunization (EPI) measles vaccine at 9 months of age. Only 41 of 403 subjects aged 1 - 2 years were negative for measles antibody before vaccination, and all became seroconverted. A serological response of more than a 2-fold increase against measles was noted in 214 (47%, 95% CI; 42.4% - 51.6%) of 458 initially seropositive individuals immunized with MRVAC and 65 (28%, 95% CI; 22.3% - 33.8%) of 234 in the control group, and geometric mean titer (GMT) after vaccination was 25.49-5.60 in MRVAC and 25.03-5.24 in control group. Seroconversion against rubella virus after immunization with MRVAC was noted in 267 (98.5%, 95% CI; 97.1% - 100%) of 271 initially seronegative subjects, similar to that after immunization with control group. GMT after immunization with MRVAC was 24.88-5.11 significantly lower than that after immunization with control vaccine (25.59-5.80). Most subject ≥ 2 years of age had rubella antibody because of MR vaccination campaign and no significant serological response was observed in initially seronegatives. MRVAC was highly immunogenic and safe vaccine and the domestic production of MR vaccine would contribute to realizing the goal of eliminating measles and rubella.
INHIBITION OF INTERFERON-g–MEDIATED MICROVASCULAR ENDOTHELIAL CELL MAJOR HISTOCOMPATIBILITY COMPLEX CLASS II GENE ACTIVATION BY HMG-COA REDUCTASE INHIBITORS

Background. Graft vascular disease, a major cause of late graft failure in cardiac transplant patients, is associated with the presence of class II major histocompatibility complex molecules on the endothelium. 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors, e.g., simvastatin, have been shown to reduce the incidence of graft vascular disease. We studied the effect of simvastatin on interferon (IFN)-g–induced human leukocyte antigen (HLA)-DR expression in human microvascular endothelial cells (MVECs). Methods and Results. Simvastatin pretreatment inhibited MVEC HLA-DR induction by IFN-g, as detected by flow cytometry. Simvastatin’s inhibitory effect was reversed by the cholesterol synthesis pathway intermediates mevalonate and geranylgeranyl pyrophosphate but not squalene, indicating the involvement of protein prenylation in this process. Reverse transcription–polymerase chain reaction analysis demonstrated that induction of class II transactivator (CIITA), and consequently, HLA-DRa mRNA, is abrogated by simvastatin. Although signal transducer and activator of transcription (STAT)-1 is a critical CIITA gene transactivator, immunofluorescence studies, Western blotting, and electrophoretic mobility shift assays demonstrated that IFN-g–induced STAT-1 phosphorylation, nuclear translocation, and DNA binding are not affected by simvastatin. However, simvastatin inhibited IFN-g–induced transactivation of a CIITA promoter IV reporter construct, indicating the involvement of this promoter in the inhibitory effect of simvastatin. Conclusions. Simvastatin pretreatment inhibits CIITA and consequent HLA-DR induction by IFN-g in MVECs through interference with protein prenylation. This inhibitory effect occurs at the level of transcription and is directed, at least in part, at the CIITA promoter IV. These results explain some of the beneficial effects of HMG-CoA reductase inhibitors in cardiac transplantation.
RECIPIENT CYTOKINE GENOTYPES FOR TNF- AND IL-10 AND THE MINOR HISTOCOMPATIBILITY ANTIGENS HY AND CD31 CODON 125 ARE NOT ASSOCIATED WITH OCCURRENCE OR SEVERITY OF ACUTE GVHD IN UNRELATED CORD BLOOD TRANSPLANTATION

Background. In HLA-identical sibling bone marrow transplantation, certain recipient cytokine gene polymorphism genotypes and minor histocompatibility differences influence the occurrence and severity of acute graft-versus-host disease (aGvHD). The present study investigated the role of cytokine tumor necrosis factor (TNF)and interleukin (IL)-10 gene polymorphisms HY, HA-1, and CD31 minor histocompatibility antigen (mHag) mismatch in the development of aGvHD after unrelated cord blood (CB) transplant (CBT). Methods. DNA samples of 115 CB recipients and their unrelated CB grafts were analyzed for genotype associated with TNF(TNFd3/d3) and IL-10 (IL-10 , 11–16) and for disparities in major and three minor histocompatibility antigens, HY, HA-1, and CD31 codon 125. Results were correlated with the incidence of aGvHD grades II to IV. Results. Neither the donor nor the recipient GvHD risk alleles TNFd3/d3 and IL-1
SPORTS CONDITIONING PROGRAMS

Willardson, J.M. Core stability training: Applications to sports conditioning programs. J. Strength Cond. Res. 21(3):979–985. 2007. —In recent years, fitness practitioners have increasingly recommended core stability exercises in sports conditioning programs. Greater core stability may benefit sports performance by providing a foundation for greater force production in the upper and lower extremities. Traditional resistance exercises have been modified to emphasize core stability. Such modifications have included performing exercises on unstable rather than stable surfaces, performing exercises while standing rather than seated, performing exercises with free weights rather than machines, and performing exercises unilaterally rather than bilaterally. Despite the popularity of core stability training, relatively little scientific research has been conducted to demonstrate the benefits for healthy athletes. Therefore, the purpose of this review was to critically examine core stability training and other issues related to this topic to determine useful applications for sports conditioning programs. Based on the current literature, prescription of core stability exercises should vary based on the phase of training and the health status of the athlete. During preseason and in-season mesocycles, free weight exercises performed while standing on a stable surface are recommended for increases in core strength and power. Free weight exercises performed in this manner are specific to the core stability requirements of sports-related skills due to moderate levels of instability and high levels of force production. Conversely, during postseason and off-season mesocycles, Swiss ball exercises involving isometric muscle actions, small loads, and long tension times are recommended for increases in core endurance. Furthermore, balance board and stability disc exercises, performed in conjunction with plyometric exercises, are recommended to improve proprioceptive and reactive capabilities, which may reduce the likelihood of lower extremity injuries.
WHAT IS THE LATEST EVIDENCE ON NURSING ORIENTATION?

NURSING ORIENTATION? It seems that nursing orientation is a constant programmatic challenge for many healthcare organizations. Is it too long? Too short? Does it engage the newly hired nurse? Will it improve retention of new hires yet keep nonproductive costs contained? Is it relevant, and does it meet the needs of a changing new employee population that is increasingly diverse, including those who represent the generational gap issue? And what does a professional development specialist do to meet the orientation needs of the newly licensed nurse? These and other questions appear frequently in the literature but often leave the professional development specialist confused about the evidence underlying orientation publications, particularly when they are narrative accounts of a single institution’s orientation. This column will highlight recent evidence about nursing orientation. A review of the literature for the past 5 years, from 2006 through July 2011, limited to nursing journals using the key words nursing and orientation in the title, resulted in 100 articles. Of the 100 articles, 47 were eliminated because they related to specialty orientations such as psychiatry. Further review deleted articles such as those on faculty or educator orientation and research conducted in Taiwan. Of the final 29 articles, 13 addressed general new nurse orientation and 16 targeted orientation for graduate nurses. Four categories were selected to organize the reviews: research, evidence-based practice, best practice, and quality improvement. The definitions used in the categorization are outlined as follows: 1. Research: A systematic investigation that includes development, testing, and evaluation, to contribute new knowledge in a field. Standard research methods, including institutional review board approval, must be evident (Department of Health and Human Services, 2007). 2. Evidence-based practice: A problem-solving approach to clinical decision making within a healthcare organization that integrates the best available scientific evidence with the best available experiential evidence (Newhouse, 2007) 3. Best practices: Generally accepted, informal techniques ormethods that are often based on commonly used practices that are described but not specifically measured in a systematic way (University of Iowa College of Nursing, 2011). For the purposes of this column, articles that described orientation programs or methods but did not include scientific methods with outcomes data fit this category. 4. Quality improvement: Steps to improve care for a specific population in a limited application, using standard quality improvement processes with outcomes data (Newhouse, Pettit, Poe, & Rocco, 2006). With these definitions in mind, the articles were organized and summarized by graduate nurse orientation and general orientation, categorized by type. Graduate nurse residency programs were not included in this review.