Miracle-dz/UniFAR-FTUs huggingface dataset:
5-Fluorouracil induces apoptotic cell death with G2 phase arrest in human breast cancer grafted in nude mice.

Treatment with 5-fluorouracil and its derivatives causes DNA double strand breaks in the S phase, and the subsequent cell death. A 5-Fluorouracil derivative (UFT), that is converted to 5-fluorouracil in vivo, was administered orally at a dose of 18 mg/kg/day to nude mice bearing human breast cancer for 28 consecutive days. The tumors on day 7, 14, 21, and 28 after treatment were examined histopathologically and by flow cytometric cell cycle analysis. UFT treatment achieved remarkable inhibition of tumor growth, and histological examination revealed significantly less mitotic figures and more apoptotic bodies throughout the treated tumors, compared to the controls. Flow cytometric study showed changes in the cell cycle outflow of treated tumor cells, involving reduced numbers of G1 phase cells and increased numbers of S and G2 phase cells, compared to the corresponding controls. The reduced growth of tumors induced by UFT is attributable to a rise in apoptotic cell death as well as a decline in producing daughter cells, i.e. mitotic activity, and 5-fluorouracil may act cytotoxically on cancer cells via apoptosis, followed by arrest at G2 phase.
Impact of Coronary Artery Bypass Graft Surgery on Health-related Quality of Life in the Elderly

of Life Coronary Artery Bypass Graft Surgery in the Elderly: A Review of Postoperative Quality Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright © 2013 American Heart Association, Inc. All rights reserved. is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Circulation doi: 10.1161/CIRCULATIONAHA.112. 000729 2013;128:2333-2343 Circulation. http://circ.ahajournals. org/content/128/21/2333 World Wide Web at: The online version of this article, along with updated information and services, is located on the
Understanding the effects of sildenafil treatment on erection maintenance and erection hardness.

INTRODUCTION Erectile dysfunction (ED) is defined as the inability to attain and/or maintain penile erection sufficient for satisfactory sexual performance. Although intuitively related, the link between erection hardness and erection maintenance has not been formally established and quantified. AIM To understand the components of erection maintenance through statistical modeling. METHODS Data from a double-blind placebo-controlled trial of fixed-dose sildenafil (100 or 50 mg, 8 weeks) with open-label extension of flexible-dose sildenafil (100 and 50 mg, 4 weeks) were analyzed. Erection maintenance was assessed with item 4 (how often erection was maintained) or item 5 (difficulty in maintaining erection) of the International Index of Erectile Function (IIEF). Erection hardness was assessed with the Erection Hardness Score. MAIN OUTCOME MEASURES Longitudinal modeling estimated mean treatment differences averaged over the double-blind phase for sildenafil 100 mg vs. placebo and 50 mg vs. placebo. Statistical mediation analysis was applied to partition the effect of sildenafil (pooled into one treatment group) on erection maintenance directly and indirectly through erection hardness. RESULTS Longitudinal mean differences for sildenafil 100 and 50 mg vs. placebo were high (P < 0.0001 for each), with large standardized effect sizes (>0.8). Mediation modeling showed that sildenafil treatment affected maintenance directly as well as indirectly via erection hardness, when measured by IIEF item 4 (direct effect, 44.6%; indirect effect, 55.4%) or IIEF item 5 (direct effect, 56.9%; indirect effect, 43.1%). CONCLUSIONS Sildenafil treatment significantly improved erection maintenance, a physiologic requirement for satisfactory sexual performance. According to our model, only approximately half of the effect of sildenafil on erection maintenance was estimated to be driven through direct effects. Rather, the effect of sildenafil on erection maintenance seems to be substantially driven by erection hardness. Therefore, achievement of optimal initial erection hardness appears to be an important treatment goal for enhancing erection maintenance and achieving successful ED treatment.
The Basement Membrane/Basal Lamina of Skeletal Muscle*

Many cells, including skeletal muscle fibers, are coated by a layer of extracellular matrix material called the basement membrane (BM). The BM, in turn, is composed of two layers: an internal, felt-like basal lamina (BL) directly linked to the plasma membrane, and an external, fibrillar reticular lamina. BMs contain protein and carbohydrate but no lipid or nucleic acid. Virtually all the protein is glycosylated, and nearly all the carbohydrate is covalently bound to protein. The fibrils of the reticular lamina are collagenous, and they are embedded in an amorphous proteoglycan-rich ground substance. The BL contains non-fibrillar collagen, non-collagenous glycoproteins, and proteoglycans (1). Initially, the BM was viewed as a static structure that provides mechanical support; essentially something for the cells to sit on. A key advance was the discovery that, because the acellular BM survives injury to associated cells, it can provide a scaffold to orient and constrain cells during regeneration (2). A more radical transformation over the past few decades was the realization that BM components play active roles and that these roles extend to developmental as well as regenerative processes (1). In skeletal muscle, these processes include myogenesis and synaptogenesis. Most recently, emphasis has shifted to a search for the matrix-associated signals and membrane-associated receptors that underlie cell-matrix interactions. The purpose of this minireview is to relate results from the new molecular analyses to the early cellular observations that motivated them. For more detailed descriptions of what happened in between, see Refs. 3–5.
Health care seeking among individuals with cough and tuberculosis: a population-based study from rural India.

SETTING Ujjain district, Madhya Pradesh, India. OBJECTIVE To describe and compare health care seeking among men and women with cough of >3 weeks, with special focus on the utilisation of private and public health care. DESIGN A population-based cross-sectional survey including 45 719 individuals aged > or = 15 years. RESULTS The prevalence of cough was respectively 2.8% and 1.2% among men and women. The majority of men and women reported seeking health care for their symptoms (69% vs. 71%), but only 23% visited a public provider at some point during their illness. A similar health care seeking pattern was found for patients diagnosed with tuberculosis (TB) in our survey. No significant differences in health care seeking were found between men and women. Only 13% of those seeking care reported having had a sputum smear examination since the onset of cough. Factors associated with sputum examination were history of TB, haemoptysis and visiting a public provider. CONCLUSION The low utilisation of public health care services and the few sputum examinations reported in this rural Indian setting illustrate the need for improved diagnostic practices as well as involvement of private providers in TB control activities.
Thrombus Burden of Deep Vein Thrombosis and Its Association with Thromboprophylaxis and D-Dimer Measurement: Insights from the APEX Trial

Abstract Background The aim of this study was to evaluate the effect of betrixaban on the occurrence of deep vein thrombosis (DVT) and also the extent of thrombus and to assess the association of baseline D-dimer with subsequent thrombus burden. Methods In the APEX trial (ClinicalTrials.gov: NCT01583218), 7,513 acutely ill hospitalized medical patients were randomly assigned to extended-duration betrixaban (35–42 days) or enoxaparin (10 ± 4 days). D-dimer concentration was measured at baseline, and mandatory lower-extremity compression ultrasonography (CUS) was performed at 35 to 42 days. The thrombus burden of DVT was assessed by the number of non-compressible vascular segments in six target proximal veins and compared between treatment groups and D-dimer categories (≥2 × upper limit of normal [ULN] versus <2 × ULN). Results Compared with enoxaparin, extended-duration betrixaban reduced the DVT risk at 35 to 42 days (any-dose: relative risk [RR] = 0.76 [95% confidence interval: 0.61–0.94]; p = 0.013; full-dose: RR = 0.70 [0.55–0.90]; p = 0.005). Patients who received betrixaban were more likely to have a lower thrombus burden (p = 0.012 for any-dose and p = 0.001 for full-dose). Elevated D-dimer at baseline was independently associated with a 2.12-fold increased risk of developing DVT (p < 0.001). A greater thrombus burden was also observed in those with D-dimer ≥ 2 × ULN compared with <2 × ULN (p < 0.0001). Conclusion Extended-duration betrixaban reduced the number of venous segments with thrombosis at 35 to 42 days compared with enoxaparin. A positive D-dimer was associated with a greater extent of thrombus burden among acutely ill medical patients who developed DVT despite receiving thromboprophylaxis. Clinical Trial Registration: URL: http://www.clinicaltrials. gov. ClinicalTrials.gov identifier: NCT01583218.
Precoding Design for Distributed Antenna Systems in Spatially Correlated Ricean Fading Channel

Three precoding schemes that are based on statistical channel state information (CSI) for distributed antenna systems (DAS) in spatially correlated channels are presented. The first two schemes exploit the channel correlation at the transmitter and the eigenstructure of the precoder to develop efficient algorithms to obtain its beamforming matrix and power allocation (PA). Based on the analysis of an average pairwise error probability bound at a low signal-to-noise ratio (SNR), the first scheme derives a suboptimal unitary matrix that helps develop an efficient modified power adaptation. The scheme has low computational complexity but encounters slight performance loss in moderate- and high-SNR regions. To reduce the performance loss, the unitary matrix is reoptimized by using the Riemannian steepest descent method in the second scheme. With the unitary matrix and modified PA, a suboptimal precoder is obtained. Using the first precoding scheme, a low-complexity precoder design is developed for Rayleigh channels, which has closed-form power control in the form of a waterfilling rule. Compared with the existing precoding scheme that relies on a fixed-point numerical search, the proposed schemes have lower complexity. Simulation results show that the proposed schemes can provide symbol error performance better than the equal-PA scheme and close to the existing precoding scheme.
Central auditory dysfunction, cognitive dysfunction, and dementia in older people.

OBJECTIVES To determine in older people the relation between auditory dysfunction and cognitive dysfunction, and if central auditory test abnormalities predict the onset of clinical dementia or cognitive decline. DESIGN Prospective population-based cohort study. SETTING Framingham Heart Study outpatient biennial examinations 18 and 21. PARTICIPANTS Members of the Framingham Heart Study cohort with normal findings from cognitive screening tests at biennial examination 18. MEASUREMENTS Peripheral audiometric thresholds and word recognition in quiet; Synthetic Sentence Identification with Ipsilateral Competing Message (SSI-ICM); Mini-Mental State Examination; and detailed neuropsychological testing of subjects with abnormal findings from the Mini-Mental State Examination. Relative risk of dementia was determined using age-adjusted Cox proportional hazards regression models. RESULTS Hearing loss significantly lowered performance on the verbal parts of the Mini-Mental State Examination. The relative risk of subsequent clinical dementia or cognitive decline was 6 in subjects with very poor scores (< 50%) in one ear on the SSI-ICM (P = .02); the relative risk was 12.5 if the poor scores were present in both ears (P = .001). CONCLUSIONS Central auditory dysfunction precedes senile dementia in a significant number of cases and may be an early marker for senile dementia. Hearing tests should be included in the evaluation of persons older than 60 years and in those suspected of having cognitive dysfunction.
Irradiation Temperature Influence on the In Situ Measured Radiation Induced Attenuation of Ge-Doped Fibers

We report an experimental investigation on the radiation-induced attenuation (RIA) in the ultraviolet-visible domain for Ge-doped optical fibers, during X-ray (10 keV) exposure at different temperatures. The objective is to characterize the impact of the irradiation temperature on the RIA levels and kinetics. Our data highlight that for dose exceeding 1 kGy(SiO2) the RIA spectrum changes with the irradiation temperature. In particular, for wavelengths below 470 nm the RIA depends both on the dose and on the irradiation temperature, whereas at higher wavelengths the RIA depends only on the dose. From the microscopic point of view the origin of this behavior is explained by a larger impact of the irradiation temperature on the Ge(1) defects generation mechanism with respect to the one of GeX defects, which appears as poorly temperature sensitive in the tested range. This finding prevents us from easily establishing a conclusive relation between the generation mechanisms of these two types of defects. The lower content of radiation induced Ge(1), in fiber irradiated at higher temperature, is supported by the electron paramagnetic resonance (EPR) results acquired after the irradiation. In situ RIA and postmortem EPR data show a significant correspondence of the Ge(1) growth as a function of the dose. Confocal microscopy luminescence experiments indicate that the non-bridging oxygen hole center concentration is higher at 473 K in comparison with those observed at 300 and 373 K.
Murine mammary tumor virus related antigen in human male mammary carcinoma

An antigen immunologically related to mouse mammary tumor virus (MuMTV) and the major envelope glycoprotein, gp52 of MuMTV, was identified in tissue sections of human male and female mammary ‐ carcinomas using the peroxidase‐antiperoxidase technique. The specificity of the reaction was established by absorption studies. Positive reactions with the gp52 antiserum were seen in mouse and human mammary carcinomas, but not in normal mammary tissues, mammary tissues with benign diseases and in other primary malignant neoplasms. Almost all (32/36, 89%) male mammary carcinomas were positive for the gp52 related antigen. A lesser proportion of tumors among female patients (14/50, 28%) were positive. The gp52 positive tumors were significantly larger than the gp52 negative tumors in female patients (P < 0.05). Gp52 positive tumors were also larger than gp52 negative tumors in male patients, but the difference was not statistically significant. Gp52 reactivity was also detected in metastatic mammary carcinoma in axillary lymph nodes of male and female patients. The presence of gp52 related antigen was not apparently related to tumor grade or lymphocytic infiltrate in the primary tumor. The data do not permit a firm conclusion regarding nodal status in men; no correlation of gp52 activity and nodal status in women was evident. These results indicate that mammary carcinomas in men as well as in women have an antigen related immunologically to MuMTV gp52. Other than tumor size, the antigen seems to be unrelated to major prognostic factors. The significance of the antigen with respect to etiologic features and prognosis in breast cancer remains to be determined.
Women's preferences for prevention of bone loss.

OBJECTIVE Despite the serious consequences of osteoporosis, few women use pharmacologic measures to prevent postmenopausal bone loss. We used an interactive computerized questionnaire to examine women's preferences for prevention of osteoporosis. METHODS We administered a choice-based conjoint analysis survey (CBCA) to consecutive early postmenopausal women in a shopping center. The questionnaire was constructed to measure preferences for pharmacologic and nonpharmacologic measures to prevent postmenopausal bone loss. Women were also given the option of choosing "none," i.e., to defer or refuse all options. Utilities were calculated based on a Hierarchical Bayes model using Monte Carlo-Markov chain algorithms. We performed simulations based on women's values for specific treatment characteristics to estimate choice. RESULTS A total of 212 women agreed to complete the survey (42% participation rate). Between 18% and 47% of the women surveyed (mean age 52+/-5 yrs) were predicted to choose once-weekly medications to prevent postmenopausal bone loss, assuming treatment confers an absolute lifetime risk reduction in fractures of at least 10%. CONCLUSION In this CBCA survey, which derived preferences based on how women make tradeoffs between specific treatment characteristics, a significant percentage of women were willing to use once-weekly medications to prevent postmenopausal bone loss.
Increase in colonic methanogens and total anaerobes in aging rats

Methanogens are present in the colons of our local Wistar rat colony. We studied the changes in concentrations of their fecal methanogenic and nonmethanogenic bacteria with age as a model of the development of these communities in humans. We found that the predominant methanogen in the rats is a Methanobrevibacter species. The log of the concentration of total anaerobes increased from 9.8/g (dry weight) at 3.0 weeks of age (shortly after weaning) to 10.7/g (dry weight) at 96 weeks (shortly before the end of the life span). In contrast, the log concentration of methanogens increased from 5.5 to 9/g (dry weight) during the same time period. Therefore, methanogens increased as a percentage of the total anaerobes from 0.005% at 3.0 weeks to 2.0% at 96 weeks. About 12 doublings of the methanogenic population and 3.3 doublings of the nonmethanogenic population took place from weaning until death. The slow increase in the ratio of methanogens to total anaerobes with age followed the same pattern in cecal contents as found in feces. There were no relationships between animal weights or fecal outputs and the increase in total anaerobe and methanogen concentrations in feces. A possible explanation for the slow increase in the Methanobrevibacter species in Wistar rats with age is a gradual shifting of the use of electrons from the reduction of CO2 to acetate by acetogens to the reduction of CO2 to CH4. The results provide the first evidence for an age-related change in the nonmethanogenic bacteria of the colon and supporting microbiological evidence for physiological studies that have shown age-related increases in colonic methane production in humans.
Cyclooxygenase‐2 inhibitor celecoxib augments chemotherapeutic drug‐induced apoptosis by enhancing activation of caspase‐3 and ‐9 in prostate cancer cells

Many tumors constitutively express high levels of the inducible form of proinflammatory enzyme, cyclooxygenase‐2 (COX‐2). Increased COX‐2 expression is associated with tumor cell resistance to many cytotoxic chemotherapy drugs. Furthermore, increased resistance to cytotoxic antitumor drugs is also known to be dependent on associated stromal cells in many tumors. We investigated whether prostate tumor‐associated stromal cells, marrow‐derived osteoblasts, affect cytotoxicity of 2 antitumor drugs, COL‐3 and docetaxel (TXTR), and whether it is dependent on COX‐2 activity. We further examined whether inhibiting the activity of COX‐2 negate the stroma‐induced decrease in drug sensitivity in tumor cells. COX‐2‐specific inhibitor celecoxib (CXB) was used to inhibit COX‐2 activity and associated alteration in cell death signaling was investigated. Coculturing PC‐3ML cells with osteoblasts decreased the cytotoxicity of the tested antitumor drugs and was associated with increased COX‐2 activity in PC‐3ML cells. A significant decrease in drug‐induced PGE2 increase and an increase in cytotoxicity were observed when cells were treated with COL‐3 or TXTR combined with CXB. Cytotoxicity of single or combination treatment increased apoptosis, which was associated with caspase‐3 and ‐9 activation, PARP cleavage, increased BAD protein, but decreased protein levels of XIAP and BCL‐xL. Oral administration of CXB (40 mg/kg) to mice with PC‐3ML tumors for 42 days increased tumor latency, decreased tumor growth and enhanced tumor control with COL‐3 or TXTR. Overall, a synergistic enhancement of antitumor activity in combination treatment was observed in vitro and an additive effect in vivo. These observations suggest a potential clinical use of combined dosing of COX‐2 inhibitors and cytotoxic drugs at lower, nontoxic dose than currently used to treat advanced prostate cancer. © 2005 Wiley‐Liss, Inc.
Novel targeted immunotherapy approaches for staphylococcal infection

Importance of the field: Staphylococcus aureus is a leading human pathogen in the hospital and the community. Many S. aureus strains are resistant to antibiotics, making treatment of S. aureus infections often very complicated. In contrast to many other bacterial pathogens, a working vaccine has never been found for S. aureus despite considerable efforts in academia and pharmaceutical companies. Areas covered in this review: The latest strategies aimed at finding a working vaccine against S. aureus, including active and passive immunization efforts in pre-clinical and clinical stages, and the molecular reasons for why it may be difficult to develop a vaccine are discussed. What the reader will gain: In addition to receiving an overview of current efforts in S. aureus vaccine research, the reader will understand that vaccine development for S. aureus may be difficult owing to the facts that S. aureus is a commensal microorganism and produces toxins that lyse white blood cells, thereby undermining a vaccine's role as a facilitator of opsonophagocytosis. Take home message: As a result of failed clinical trials with monovalent traditional vaccines, recent developments include a shift towards the potential use of polyvalent formulas and therapeutic antibodies and more systematic selection of optimal antigens.
Competencies measured in assessment centers: Predictors oftransformational leadership and leader's effectiveness

The objective of this study is to explore which competencies predict leader effectiveness. Based on theory and job analysis, we observed the effects of five leaders' competencies (achievement orientation, problem analysis and problem solving, social sensitivity, influence, and integrity) on three indicators of effectiveness (perceived leader's effectiveness, leadership emergence, and team performance). Furthermore, we examined whether transformational leadership mediates these effects. We collected the data during an interuniversity student team competition. A total of 57 team leaders and 364 team members participated in the study. At the beginning of the competition, we measured the leaders' competencies through assessment centers. Each leader was assessed by 4 trained assessors in a one day long assessment center consisting of multiple individual and group model situations. After 6 months of teamwork, we measured the perceived leaders' effectiveness, leadership emergence and transformational leadership using questionnaires, and we estimated the teams' performance based on the ranking of the teams in the competition. The results show that leader achievement orientation is a significant predictor of perceived leader effectiveness, leadership emergence and team performance. The other four competencies do not predict leader effectiveness. There is no relation between competencies and transformational leadership; therefore, transformational leadership does not mediate the relation between competencies and effectiveness. The advantages of this study were that we obtained the data regarding the competencies and effectiveness from three different sources and that we measured competencies before the teamwork began. An average of more than 6 subordinates per leader ensures highly reliable evaluations of leaders' transformational leadership, perceived effectiveness and leadership emergence. The results can be applied to leader selection for short-term team projects.