Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical trial results of a HER2/neu (E75) vaccine to prevent recurrence in high-risk breast cancer patients.

PURPOSE E75 is an immunogenic peptide from the HER2/neu protein that is highly expressed in breast cancer. We are conducting a clinical trial of an E75 + granulocyte-macrophage colony-stimulating factor vaccine to assess safety, immunologic response, and the prevention of clinical recurrences in patients with disease-free, node-positive breast cancer (NPBC). PATIENTS AND METHODS Fifty-three patients with NPBC were enrolled and HLA typed. HLA-A2+ patients (n = 24) were vaccinated, and HLA-A2- patients (n = 29) are observed prospectively as clinical controls. Local/systemic toxicities, immunologic responses, and time to recurrence are being measured. RESULTS Only minor toxicities have occurred (one grade 3 [4%]). All patients have demonstrated clonal expansion of E75-specific CD8+T cells that lysed HER2/neu-expressing tumor cells. An optimal dosage and schedule have been established. Patients have developed delayed-type hypersensitivity reactions to E75 postvaccination compared with controls (33 v 7 mm; P < .01). HLA-A2+ patients have been found to have larger, more poorly differentiated, and more hormonally insensitive tumors compared to HLA-A2- patients. Despite this, the only two deaths have occurred in the control group. The disease-free survival in the vaccinated group is 85.7% compared to 59.8% in the controls at 22 months' median follow-up with a recurrence rate of 8% compared to 21%, respectively (P < .19). Median time to recurrence in the vaccinated patients was prolonged (11 v 8 months), and recurrence correlated with a weak delayed-type hypersensitivity response. CONCLUSION This HER2/neu (E75) vaccine is safe and effective in eliciting a peptide-specific immune response in vivo. Induced HER2/neu immunity seems to reduce the recurrence rate in patients with NPBC.
Cancer survival in China, 2003–2005: A population‐based study

Limited population‐based cancer registry data available in China until now has hampered efforts to inform cancer control policy. Following extensive efforts to improve the systematic cancer surveillance in this country, we report on the largest pooled analysis of cancer survival data in China to date. Of 21 population‐based cancer registries, data from 17 registries (n = 138,852 cancer records) were included in the final analysis. Cases were diagnosed in 2003–2005 and followed until the end of 2010. Age‐standardized relative survival was calculated using region‐specific life tables for all cancers combined and 26 individual cancers. Estimates were further stratified by sex and geographical area. The age‐standardized 5‐year relative survival for all cancers was 30.9% (95% confidence intervals: 30.6%‐31.2%). Female breast cancer had high survival (73.0%) followed by cancers of the colorectum (47.2%), stomach (27.4%), esophagus (20.9%), with lung and liver cancer having poor survival (16.1% and 10.1%), respectively. Survival for women was generally higher than for men. Survival for rural patients was about half that of their urban counterparts for all cancers combined (21.8% vs. 39.5%); the pattern was similar for individual major cancers except esophageal cancer. The poor population survival rates in China emphasize the urgent need for government policy changes and investment to improve health services. While the causes for the striking urban‐rural disparities observed are not fully understood, increasing access of health service in rural areas and providing basic health‐care to the disadvantaged populations will be essential for reducing this disparity in the future.
Cloning and characterization of the regulatory Bacillus subtilis competence genes comA and comB

comA and comB are Bacillus subtilis competence genes that are identified by insertions of Tn917lac. They are classified as early genes because of their expression throughout growth; the expression of late com genes increases sharply during the transition to the stationary phase. The comA and comB determinants were cloned, and the 5' and 3' termini of their transcripts were localized by low-resolution S1 nuclease protection experiments. comA and comB were found by Southern blotting to be localized near one another, but they were nevertheless apparently transcribed independently. Epistatic relationships among the com genes were explored by using the beta-galactosidase expressed from transcriptional fusions as a marker. Late com genes were found to be dependent on the products of comA, comB, and sin for their expression. The sin gene is a transcriptional regulator that is required for the development of competence (N. K. Gaur, E. Dubnau, and I. Smith, J. Bacteriol. 168:860-869, 1986).
The efficacy of early adjuvant radiation therapy for pT3N0 prostate cancer: a matched-pair analysis.

PURPOSE This study examines the effect of adjuvant radiation therapy (RT) on outcome in patients with pT3N0 prostate cancer and makes comparisons to a matched control group. METHODS AND MATERIALS At our center, 149 patients undergoing radical prostatectomy were found to have pT3N0 prostate cancer, had an undetectable postoperative prostate-specific antigen (PSA) level, and had no immediate hormonal therapy. Fifty-two patients received adjuvant RT within 3 to 6 months of surgery. Ninety-seven underwent radical prostatectomy alone and were observed until PSA failure. From these two cohorts, we matched patients 1:1 according to preoperative PSA (<10 ng/ml vs. >10 ng/ml), Gleason score (<7 vs. > or =7), seminal vesicle invasion, and surgical margin status. Seventy-two patients (36 pairs) were included in the analysis. Median follow-up time was 41 months. We calculated a matched-pairs risk ratio for cumulative risk of PSA relapse (a rise above 0.2 ng/ml). RESULTS After controlling for the prognostic factors by matching, there was an 88% reduction (95% confidence interval [CI]: 78-93%) in the risk of PSA relapse associated with adjuvant RT. The 5-year freedom from PSA relapse rate was 89% (95% CI: 76-100%) for patients receiving adjuvant RT as compared to 55% (95% CI: 34-79%) for those undergoing radical prostatectomy alone. CONCLUSIONS These data suggest that adjuvant RT for pT3N0 prostate cancer may significantly reduce the risk of PSA failure as compared to radical prostatectomy alone. Its effect on clinical outcome awaits further follow-up.
Cilostazol Reduces Atherosclerosis by Inhibition of Superoxide and Tumor Necrosis Factor-α Formation in Low-Density Lipoprotein Receptor-Null Mice Fed High Cholesterol

This study shows that 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl) butoxy]-3,4-dihydro-2(1H)-quinolinone (cilostazol) suppresses the atherosclerotic lesion formation in the low-density lipoprotein receptor (Ldlr)-null mice. Ldlr-null mice fed a high cholesterol diet showed multiple plaque lesions in the proximal ascending aorta including aortic sinus, accompanied by increased macrophage accumulation with increased expression of vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1). Supplementation of cilostazol (0.2% w/w) in diet significantly decreased the plaque lesions with reduced macrophage accumulation and suppression of VCAM-1 and MCP-1 in situ. Increased superoxide and tumor necrosis factor-α (TNF-α) production were significantly lowered by cilostazol in situ as well as in cultured human umbilical vein endothelial cells (HUVECs). TNF-α-induced increased inhibitory κBα degradation in the cytoplasm and nuclear factor-κB (NF-κB) p65 activation in the nuclei of HUVECs were reversed by cilostazol (1 ∼ 100 μM) as well as by (E)-3[(4-t-butylphenyl)sulfonyl]-2-propenenitrile (BAY 11-7085) (10 μM), suggesting that cilostazol strongly inhibits NF-κB activation and p65 translocation into the nuclei. Furthermore, in gel shift and DNA-binding assay, cilostazol inhibited NF-κB/DNA complex and nuclear DNA-binding activity of the NF-κB in the nuclear extracts of the RAW 264.7 cells. Taken together, it is suggested that the anti-atherogenic effect of cilostazol in cholesterol-fed Ldlr-null mice is ascribed to its property to suppress superoxide and TNF-α formation, and thereby reducing NF-κB activation/transcription, VCAM-1/MCP-1 expressions, and monocyte recruitments.
Effects of Plyometric Training and Beta-Alanine Supplementation on Maximal-Intensity Exercise and Endurance in Female Soccer Players

Abstract Plyometric training and beta-alanine supplementation are common among soccer players, although its combined use had never been tested. Therefore, a randomized, double-blind, placebo-controlled trial was conducted to compare the effects of a plyometric training program, with or without beta-alanine supplementation, on maximal-intensity and endurance performance in female soccer players during an in-season training period. Athletes (23.7 ± 2.4 years) were assigned to either a plyometric training group receiving a placebo (PLACEBO, n = 8), a plyometric training group receiving beta-alanine supplementation (BA, n = 8), or a control group receiving placebo without following a plyometric training program (CONTROL, n = 9). Athletes were evaluated for single and repeated jumps and sprints, endurance, and change-of-direction speed performance before and after the intervention. Both plyometric training groups improved in explosive jumping (ES = 0.27 to 1.0), sprinting (ES = 0.31 to 0.78), repeated sprinting (ES = 0.39 to 0.91), 60 s repeated jumping (ES = 0.32 to 0.45), endurance (ES = 0.35 to 0.37), and change-of-direction speed performance (ES = 0.36 to 0.58), whereas no significant changes were observed for the CONTROL group. Nevertheless, compared to the CONTROL group, only the BA group showed greater improvements in endurance, repeated sprinting and repeated jumping performances. It was concluded that beta-alanine supplementation during plyometric training may add further adaptive changes related to endurance, repeated sprinting and jumping ability.
Quit for keeps: tailored smoking cessation guides for pregnancy and beyond

Although health care providers appear to be an obvious choice for delivering smoking cessation education, they often lack the resources, training, and time to provide anything more than a recommendation to quit and generic pamphlets for reinforcement. Traditionally, this type of material is designed to include information for many potential users, thus making it difficult for an individual to find the pieces most relevant to them. In contrast, tailored print materials provide only information which is relevant to a subject, making it far more usable. One study assessing tailored print messages found a threefold increase in cessation rates among patients in a family practice setting, four months after receipt of tailored versus untailored smoking cessation messages.1 Numerous other studies, targeting a number of different populations, have also shown that tailored messages are an effective intervention for smoking cessation.2 In tailoring, we use individual patient responses to select only relevant behaviour change messages. These messages provide information specific to an individual's needs and interests and can reinforce messages from health professionals. Because they are personalised, tailored materials offer a potentially superior alternative to generic materials designed to reach a broad audience. Quit for Keeps used a pre-test/post-test experimental design to test the effects of tailored interventions on pregnant smokers. Participants in this study included 92 women enrolled at the Taubman obstetrics and gynaecology (ob/gyn) clinic at the University of Michigan and 81 women enrolled at the ob/gyn clinic at the University of North Carolina hospital from December 1996 to December 1997. Eligible participants were those who reported having smoked at least 100 cigarettes in their lifetime and who were either still smoking or had quit since becoming pregnant. Subjects were screened for eligibility during the New to the Nurse orientation program in North Carolina or during their first pre-natal …
Muscle categorization using PDF estimation and Naive Bayes classification

The structure of motor unit potentials (MUPs) and their times of occurrence provide information about the motor units (MUs) that created them. As such, electromyographic (EMG) data can be used to categorize muscles as normal or suffering from a neuromuscular disease. Using pattern discovery (PD) allows clinicians to understand the rationale underlying a certain muscle characterization; i.e. it is transparent. Discretization is required in PD, which leads to some loss in accuracy. In this work, characterization techniques that are based on estimating probability density functions (PDFs) for each muscle category are implemented. Characterization probabilities of each motor unit potential train (MUPT) are obtained from these PDFs and then Bayes rule is used to aggregate the MUPT characterization probabilities to calculate muscle level probabilities. Even though this technique is not as transparent as PD, its accuracy is higher than the discrete PD. Ultimately, the goal is to use a technique that is based on both PDFs and PD and make it as transparent and as efficient as possible, but first it was necessary to thoroughly assess how accurate a fully continuous approach can be. Using Gaussian PDF estimation achieved improvements in muscle categorization accuracy over PD and further improvements resulted from using feature value histograms to choose more representative PDFs; for instance, using log-normal distribution to represent skewed histograms.
Draft Genome Sequence of Mycobacterium bovis Strain D-10-02315 Isolated from Wild Boar

ABSTRACT Mycobacterium bovis is the etiologic agent of bovine tuberculosis, a chronic infectious disease, affecting livestock, wild animals, and sometimes humans. We report the draft genome sequence of a Mycobacterium bovis strain isolated from wild boar of spoligotype SB0120 (or BCG-like) also present in wildlife-livestock multi-host systems.
Binocular sighting ocular dominance changes with different angles of horizontal gaze.

BACKGROUND AND PURPOSE Ocular dominance testing is generally carried out in the primary position. A change of eye dominance when viewing in the contralateral field of horizontal gaze has recently been reported. The purpose of this study was to determine whether this occurs with other tests of eye dominance. METHODS Ten right handed females (mean age 21.6 +/-0.8 years) with normal binocular single vision and right eye ocular dominance in primary position were tested for ocular dominance on three tests (pointing, hole-in-card, Miles ABC) performed fixing at positions at 10 degree intervals from 40 degrees left gaze to 40 degrees right gaze, with the head stationary. Four trials were undertaken in each position for each test. RESULTS Not all participants showed a change in dominance in left gaze on all of the tests. However, a change did occur at a median of 30 degrees for the hole- in-card and Miles ABC tests and 20 degrees for the pointing test. Examining the position of change across the 3 tests, a borderline "statistically significant" difference occurred (p=0.055, Friedman test). A "statistically significant" difference was shown between the hole-in-card and pointing tests (p=0.041, Wilcoxon signed ranks test). For pointing versus Miles ABC, p=0.084; and hole-in-card versus Miles ABC, p=0.705. CONCLUSIONS A change in eye dominance occurs when viewing in the contralateral field. Differences may exist in the angle at which this occurs due to the different conditions of the various tests for ocular dominance.
Total Synthesis and Biological Assessment of Benzimidazole‐Based Analogues of Epothilone A: Ambivalent Effects on Cancer Cell Growth Inhibition

Microtubule-stabilizing agents are potent inhibitors of human cancer cell proliferation, and several compounds of this type have been developed into clinically important anticancer drugs or are currently undergoing human clinical trials. 2] So far, natural products from a variety of organisms (plants, bacteria, marine organisms) have proven to be the most productive source of new microtubule stabilizers, and several new lead structures with microtubule-stabilizing properties have been identified over the last few years. Among these, epothilones (Epo) A and B are the most extensively investigated, and
Overlapping substrate specificities and tissue distribution of cytochrome P450 3A and P‐glycoprotein: Implications for drug delivery and activity in cancer chemotherapy

A great challenge to the continuing search for more efficient and specific anticancer drugs is the unified response by tumor cells to rid themselves of these agents, a process loosely labeled multidrug resistance. While multidrug resistance has now become synonymous with the P-glycoprotein (P-gp) drug-efflux pump, in reality this process encompasses the full range of cellular responses to xenobiotics, including upregulation of drug-metabolism processes [I ,2]. Research in our laboratory has focused on cytochrome P450(CYP)3A, the enzyme responsible for phase I metabolism of over 50% of drugs administered to humans (National Academy of Sciences, Institute of Medicine workshop: "Enzymes of Drug Metabolism: Importance to Drug Safety and Efficacy," January 25 and 26, 1993) and particularly the contribution of intestinal CYP3A-mediated metabolism to the bioavailability o f orally administered drugs such as cyclosporine. The importance of intestinal CYP3A in decreasing oral-drug bioavailability is even now not recognized by many drug-delivery scientists, who have previously been concerned exclusively with the physicochemical aspects of drug absorption. Similarly, such scientists are just beginning to appreciate that P-gp is expressed at high levels on the apical surfaces of columnar epithelial cells in the jejunum [3] and is also expected to play a part in the absorption of many drugs. Previous reports have noted that various inhibitors of P-gp activity in tumor cells are also CYP3A substrates [4,51, and the more detailed investigation described here revealed a number of striking overlaps between CYP3A and P-gp that suggest that these enzymes have complementary roles in the pharrnacokinetics of drug absorption and elimination that are particularly relevant to cancer chemotherapy.
CONTRASTING PATTERNS OF SYNONYMOUS AND NONSYNONYMOUS SEQUENCE EVOLUTION IN ASEXUAL AND SEXUAL FRESHWATER SNAIL LINEAGES

Abstract In asexual lineages, both synonymous and nonsynonymous sequence polymorphism may be reduced due to severe founder effects when asexual lineages originate. However, mildly deleterious (nonsynonymous) mutations may accumulate after asexual lineages are formed, because the efficiency of purifying selection is reduced even in the nonrecombining mitochondrial genome. Here we examine patterns of synonymous and nonsynonymous mitochondrial sequence polymorphism in asexual and sexual lineages of the freshwater snail Campeloma. Using clade-specific estimates, we found that synonymous sequence polymorphism was significantly reduced by 75% in asexuals relative to sexuals, whereas nonsynonymous sequence polymorphism did not differ significantly between sexuals and asexuals. Two asexual clades had high negative values for Tajima's D statistic. Coalescent simulations confirmed that various bottleneck scenarios can account for this result. We also used branch-specific estimates of the ratio of amino acid to silent substitutions, Ka/Ks. Our study revealed that Ka/Ks ratios are six times higher in terminal branches of independent asexual lineages compared to sexuals. Coalescent-based reconstruction of gene networks for all sexual and asexual clades indicated that nonsynonymous mutations occurred at a higher frequency in recently derived asexual haplotypes. These findings suggest that patterns of synonymous and nonsynonymous nucleotide polymorphism in asexual snail lineages may be shaped by both severe founder effect and relaxed purifying selection.
Flexibility of NS5 Methyltransferase-Polymerase Linker Region Is Essential for Dengue Virus Replication

ABSTRACT We examined the function of the conserved Val/Ile residue within the dengue virus NS5 interdomain linker (residues 263 to 272) by site-directed mutagenesis. Gly substitution or Gly/Pro insertion after the conserved residue increased the linker flexibility and created slightly attenuated viruses. In contrast, Pro substitution abolished virus replication by imposing rigidity in the linker and restricting NS5's conformational plasticity. Our biochemical and reverse genetics experiments demonstrate that NS5 utilizes conformational regulation to achieve optimum viral replication.
Expulsion of demecolcine‐induced micronuclei from mouse bone marrow polychromatic erythrocytes

The mouse micronucleus test is a valuable tool for evaluating in vivo chromosome damage produced by test articles in polychromatic erythrocytes of bone marrow. Compounds that are clastogens, such as cyclophosphamide, induce micronuclei that are smaller than those induced by compounds that are spindle poisons, such as demecolcine. In vitro studies have previously shown that the frequency of mitomycin C‐ and vincristine‐induced micronuclei in mouse L‐929 cells was reduced due to micronuclear extrusion following treatment with cytochalasin B. The current study shows that micronuclei are also expelled in vivo, that expulsion is dependent upon micronuclear size, and that observation of these extruded micronuclei is dependent upon the method of sample preparation.
Determinants of HIV antibody testing among selected groups of Chinese residents in Hong Kong

HIV testing is promoted to the public as a tool for HIV prevention in many countries. However, the patterns and determinants of HIV antibody testing among the Chinese people are unknown. To describe the prevalence and determinants of HIV antibody testing amongst the Hong Kong Chinese a cross-sectional anonymous survey was carried out among 1027 subjects from different population groups (airport travellers, business sector workers, service sector workers, university staff, and STD clinic attendees). Subjects were categorized into either 'STD population' (respondents from STD clinics) versus 'all others' (respondents from other settings) groups. Forty-five percent of the respondents reported ever having had a test for HIV antibody. 'STD population' group members were almost three times more likely to have had an HIV test than were 'all others' group members (77% vs 20%). After adjustments, 'STD population' group members who reported having tested for HIV were more often aged 45 years or older, alcohol drinkers, with high self-efficacy scores, and inconsistent condom users; members in the 'all others' group, more often had had sex with strangers, drank alcohol, and favoured having multiple sex partners. Awareness among the public about the risk behaviours for HIV should be enhanced and efforts should be made to reduce high-risk behaviours among those tested by emphasizing the importance of maintaining safer sex behaviour and having follow-up tests during post-test counselling.