Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of metabolic modulation by trimetazidine on left ventricular function and phosphocreatine/adenosine triphosphate ratio in patients with heart failure.

AIMS The addition of trimetazidine to standard treatment has been shown to improve left ventricular (LV) function in patients with heart failure. The aim of this study is to non-invasively assess, by means of in vivo 31P-magnetic resonance spectroscopy (31P-MRS), the effects of trimetazidine on LV cardiac phosphocreatine and adenosine triphosphate (PCr/ATP) ratio in patients with heart failure. METHODS AND RESULTS Twelve heart failure patients were randomized in a double-blind, cross-over study to placebo or trimetazidine (20 mg t.i.d.) for two periods of 90 days. At the end of each period, all patients underwent exercise testing, 2D echocardiography, and MRS. New York Heart Association (NYHA) class, ejection fraction (EF), maximal rate-pressure product, and metabolic equivalent system (METS) were evaluated. Relative concentrations of PCr and ATP were determined by cardiac 31P-MRS. On trimetazidine, NYHA class decreased from 3.04+/-0.26 to 2.45+/-0.52 (P = 0.005), whereas EF (34+/-10 vs. 39+/-10%, P = 0.03) and METS (from 7.44+/-1.84 to 8.78+/-2.72, P = 0.03) increased. The mean cardiac PCr/ATP ratio was 1.35+/-0.33 with placebo, but was increased by 33% to 1.80+/-0.50 (P = 0.03) with trimetazidine. CONCLUSION Trimetazidine improves functional class and LV function in patients with heart failure. These effects are associated to the observed trimetazidine-induced increase in the PCr/ATP ratio, indicating preservation of the myocardial high-energy phosphate levels.
Cotton Policy in China

This report examines China’s 2011-13 attempt to maintain a high level of price support for its cotton producers, analyzing the policy’s motivation, its consequences to date, and the impacts of various adjustment alternatives China might pursue. With China’s wages rising rapidly in recent years, cotton production costs there have been rising faster than in the rest of the world. Rising costs both helped motivate China’s policymakers to strengthen their price support for cotton production in 2011 and ensured that the policy ultimately proved unsustainable. After several years of sharply lower cotton consumption and sharply rising state-owned stockpiles of cotton, China in 2014 began switching producer support to direct subsidies, and focusing support on producers in the largest producing region, Xinjiang. Additional reforms include plans to restore market forces to a leading role in determining China’s cotton prices. But China’s large role in world cotton markets and the unprecedented size of the government’s stocks mean that difficult choices lie ahead for China’s policymakers. Policy decisions in China will continue to have a significant impact on the rest of the world, and lower Chinese import quotas for cotton could reduce world cotton prices significantly.
Association of Epstein-Barr virus, human papilloma virus, and cytomegalovirus with nine nasopharyngeal carcinoma cell lines.

BACKGROUND Epstein-Barr virus (EBV) has been proposed to be closely associated with nasopharyngeal carcinoma (NPC). To evaluate the actual relationship, EBV was analyzed in nine established NPC cell lines and in four original NPC biopsy specimens. EXPERIMENTAL DESIGN We used Southern blot analysis alone or after polymerase chain reaction to determine whether EBV was present in our NPC cell lines. We also used in situ nucleic acid hybridization and in situ polymerase chain reaction to identify EBV in 4 original biopsy specimens. For comparison, we investigated the cell lines for the presence of human papilloma virus type 16 (HPV-16) and human cytomegalovirus (HCMV). RESULTS Southern blots alone for detection of 3 viruses in 9 cell lines were all negative. PCR plus Southern blotting revealed that 5 cell lines contained EBV in earlier passages, and all became negative in later passages. Some cell lines also contained HPV-16 and HCMV. At earlier passages, some cell lines contained EBV, HPV-16, and HCMV concurrently. Three out of four biopsy specimens contained EBV in certain tumor cells, lymphocytes, and glandular epithelia. CONCLUSIONS These findings indicate that EBV, HPV-16, and HCMV may be present in certain NPC cell lines and in only a small fraction of each positive cell line, and that a cell line may contain these three viruses concurrently. EBV is present not only in a fraction of tumor cells, but also in some lymphocytes and glandular epithelia in biopsy specimens. It is present as an episomal form but not as an integrated form in the infected cells, suggesting that the carcinogenesis of non-EBV containing NPC tumor cells is not related to EBV infection.
The Impact of Section 302 and 404(B) Internal Control Disclosures on Prospective Investors' Judgments and Decisions: An Experimental Study

This paper reports the results of an experiment designed to investigate participants' reaction to quarterly and annual internal control disclosures. Quarterly disclosures include managers' disclosure of no control deficiencies, a significant deficiency, or a material weakness. Annual disclosures include the auditors' opinion on internal control, which either affirms managers' earlier disclosure or reveals new information. We find that participants react negatively to the disclosure of a material weakness, as might be expected. Participants invest less in a target company when internal control is ineffective rather than effective. By comparison, participants do not react negatively to the disclosure of a significant deficiency. Indeed, we find that they react positively to such disclosure accompanied by a clean (unqualified) audit opinion on internal control. Subsequent analyses indicate that participants' investment decisions are affected by their assessments of the reliability of financial statements and the credibility of management.
Comparison of weekly treatment of postmenopausal osteoporosis with alendronate versus risedronate over two years.

OBJECTIVE A 1-yr extension of the Fosamax Actonel Comparison Trial was completed to compare changes in bone mineral density (BMD), bone turnover, and upper gastrointestinal tolerability over 2 yr of treatment. DESIGN This was a randomized, double-blind extension conducted at 72 U.S. sites. PATIENTS AND METHODS Of the 1053 women who completed yr 1, 833 postmenopausal women with low BMD entered the extension, continuing their same treatment allocation [once-weekly (OW) alendronate 70 mg or OW risedronate 35 mg]. Changes in BMD at the hip trochanter, total hip, femoral neck, and lumbar spine and in markers of bone turnover were compared at 24 months. Tolerability was assessed by adverse experience reporting. RESULTS Alendronate produced greater increases from baseline in BMD at 24 months than did risedronate at the trochanter (alendronate, 4.6%; risedronate, 2.5%, P < 0.001) as well as at all other BMD sites. Significantly more alendronate than risedronate patients had measured BMD increases of 0% or more and 3% or more at all BMD sites (P < 0.001), and fewer alendronate patients had measured decreases of 3% or more at all BMD sites. Significantly greater reductions in all biochemical markers of bone turnover occurred with alendronate, compared with risedronate. No differences were seen in occurrence or discontinuations due to upper gastrointestinal adverse experiences. CONCLUSIONS Patients receiving 70 mg OW alendronate had greater gains in BMD, were more likely to maintain or gain BMD, and had greater reductions in bone turnover markers than patients receiving 35 mg OW risedronate after 24 months, with no differences in upper gastrointestinal tolerability.
Hepatocellular carcinoma repression by TNFα‐mediated synergistic lethal effect of mitosis defect‐induced senescence and cell death sensitization

Hepatocellular carcinoma (HCC) is a cancer lacking effective therapies. Several measures have been proposed to treat HCCs, such as senescence induction, mitotic inhibition, and cell death promotion. However, data from other cancers suggest that single use of these approaches may not be effective. Here, by genetic targeting of Survivin, an inhibitor of apoptosis protein (IAP) that plays dual roles in mitosis and cell survival, we identified a tumor necrosis factor alpha (TNFα)‐mediated synergistic lethal effect between senescence and apoptosis sensitization in malignant HCCs. Survivin deficiency results in mitosis defect‐associated senescence in HCC cells, which triggers local inflammation and increased TNFα. Survivin inactivation also sensitizes HCC cells to TNFα‐triggered cell death, which leads to marked HCC regression. Based on these findings, we designed a combination treatment using mitosis inhibitor and proapoptosis compounds. This treatment recapitulates the therapeutic effect of Survivin deletion and effectively eliminates HCCs, thus representing a potential strategy for HCC therapy. Conclusion: Survivin ablation dramatically suppresses human and mouse HCCs by triggering senescence‐associated TNFα and sensitizing HCC cells to TNFα‐induced cell death. Combined use of mitotic inhibitor and second mitochondrial‐derived activator of caspases mimetic can induce senescence‐associated TNFα and enhance TNFα‐induced cell death and synergistically eliminate HCC. (Hepatology 2016;64:1105‐1120)
Facilitating Comprehensive Assessment of 12-Step Experiences: A Multidimensional Measure of Mutual-Help Activity

Existing measures of 12-Step mutual-help activity typically capture only a narrow range of experiences and combine fellowships with explicitly different substance-specific emphases (e.g., Alcoholics vs. Narcotics Anonymous). To help expand our knowledge in this important area, the authors report on the development and use of a comprehensive multidimensional measure of 12-Step experiences in two clinical samples of young adults and adolescents (N = 430). One-week test–retest reliability was verified on a subsample. Results indicated high content validity and reliability across seven dimensions of experience (meeting attendance, meeting participation, fellowship involvement, step work, mandated attendance, affiliation, and safety), and the measure successfully discriminated between samples on anticipated activity levels. This measure provides rich data on mutual-help activities and deepens our understanding of individuals' experiences across different 12-Step organizations.
Systematic review and meta-analysis of school-based obesity interventions in mainland China

Background Numerous school-based interventions for childhood obesity have been emerging in mainland China in recent decades, but little is known about the effectiveness of such interventions. This study aims to assess the effectiveness of school-based interventions for childhood obesity conducted in mainland China. Methods A systematic search was undertaken in eight databases to identify both randomized and non-randomized controlled trials from January 1990 to December 2015 examining the effectiveness of school-based obesity interventions. A random effects meta-analysis was conducted assessing the impact of included interventions on (body mass index) BMI. The quality of each included studies were assessed using Effective Public Health Practice Project Quality Assessment Tool. A P value <0.05 (two-sided) was considered statistically significant. Result Of the seventy-six included studies, we found physical activity and health education were the two most common components of interventions. More treatment studies were effective compared with prevention studies (85.0% vs. 58.3%). Comprehensive interventions involving physical activity and health education appeared more effective than the physical activity only interventions in both obesity treatment and prevention studies. The meta-analyses showed comprehensive interventions involving physical activity and health education had larger effect on the change of BMI than physical activity only interventions (treatment studies: -1.80 kg/m2 (95% CI: -2.15,-1.44) vs. -0.91 kg/m2 (95% CI: -1.15,-0.67); prevention studies: -0.19 kg/m2 (95% CI: -0.27, -0.11) vs. +0.05 kg/m2 (95% CI: -0.04, +0.15)). Conclusions Comprehensive school-based interventions may assist in tackling the rising prevalence of childhood obesity in mainland China.
Debt Financing,Technology Innovation and Oligopoly Competition

In a three-stage complete information dynamic game model,the article studies that enterprise's debt financing strategy imposes strategic effect on technology innovation with spillover and quantity decision under demand uncertainty,at the same time,we compare the two competition equilibrium outcomes between being debt financing and not being debt financing.The research show that in addition to being affected by the spillover effect of technology innovation,debt-financing decision has important effect on enterprise's technology innovation action;the enterprise's quantity decision is affected by both debt financing and technology innovation.
Crystal Structure of an Antibody Bound to an Immunodominant Peptide Epitope: Novel Features in Peptide-Antibody Recognition1

The crystal structure of Fab of an Ab PC283 complexed with its corresponding peptide Ag, PS1 (HQLDPAFGANSTNPD), derived from the hepatitis B virus surface Ag was determined. The PS1 stretch Gln2P to Phe7P is present in the Ag binding site of the Ab, while the next three residues of the peptide are raised above the binding groove. The residues Ser11P, Thr12P, and Asn13P then loop back onto the Ag-binding site of the Ab. The last two residues, Pro14P and Asp15P, extend outside the binding site without forming any contacts with the Ab. The PC283-PS1 complex is among the few examples where the light chain complementarity-determining regions show more interactions than the heavy chain complementarity-determining regions, and a distal framework residue is involved in Ag binding. As seen from the crystal structure, most of the contacts between peptide and Ab are through the five residues, Leu3-Asp4-Pro5-Ala6-Phe7, of PS1. The paratope is predominantly hydrophobic with aromatic residues lining the binding pocket, although a salt bridge also contributes to stabilizing the Ag-Ab interaction. The molecular surface area buried upon PS1 binding is 756 Å2 for the peptide and 625 Å2 for the Fab, which is higher than what has been seen to date for Ab-peptide complexes. A comparison between PC283 structure and a homology model of its germline ancestor suggests that paratope optimization for PS1 occurs by improving both charge and shape complementarity.
Emerging rickettsial infections in Sri Lanka: the pattern in the hilly Central Province

Summary Objectives To identify different rickettsial infections using a specific immunofluorescent technique in patients clinically diagnosed as ‘typhus fever’ in the Central Province of Sri Lanka, and to define the clinical picture, assess the severity of infection and to determine the pattern of geographical distribution of the infections of the hospital‐based patients.
Perspectives on restoring health shared by Cree women, Alberta, Canada.

The purpose of this study was to explore nehiyaw iskwêwak (Cree women's) perceptions and beliefs about how to restore balance to health. Fifteen indigenous women from Northern Alberta, Canada, participated in a 3-day cultural retreat on beauty and art in British Columbia, Canada, in May 2015. At the end of the retreat, these women were invited to participate in a talking circle and asked, 'What does restoring balance look like? ' A constructivist grounded theory approach was used to explore individual and collective perspectives on restoring health. Nehiyaw iskwêwak provided a vision of health using metaphors from the natural environment. Starting points and core characteristics of health were grounded in relationship with self, others, place and the land, suggesting interventions grounded in land-based pedagogy and focused on restoring relationship and secure attachment might be effective for this population. Nehiyaw iskwêwak also said interventions should start at the individual level; as the individual restores balance mentally, emotionally, physically and spiritually, a long-term ripple effect can be initiated through the generations and community when these women in turn support the strengthening and nurturing of relations (e.g. parents, siblings, friends, children, grandchildren) for the next seven generations.
Models for the in-host dynamics of malaria revisited: errors in some basic models lead to large over-estimates of growth rates

The mathematical model of the in-host dynamics for malaria parasites of Anderson, R. M. , May, R. M. & Gupta, S. (1989), Parasitology99 (Suppl.) S59–S79, and subsequently used by other authors, contains an error. This leads to very substantial over-estimates in parasite growth rates. A corrected form of the model is presented in this paper.
The impact of morin, a natural flavonoid, on cyclophosphamide-induced changes in the oxidative stress parameters in rat livers.

BACKGROUND Cyclophosphamide (CPX) has many adverse effects, partly due to oxidative stress induction in various tissues. Morin is one of the natural flavonoids with strong antioxidant properties. OBJECTIVES The aim of the current research was to estimate the influence of morin on changes in antioxidant parameters in rat livers after cyclophosphamide administration. MATERIAL AND METHODS The study was performed on Wistar rats. The rats in Group C received 0.9% saline; those in Group CX received cyclophosphamide (CPX); and those in Group M-CX received CPX with morin. Cyclophosphamide and morin were given by gastric gavage for 10 consecutive days at doses of 15 mg/kg and 100 mg/kg, respectively. Malondialdehyde (MDA) and glutathione (GSH) concentrations, superoxide dismutase (SOD) activity and catalase (CAT) activity were determined in liver tissue homogenates. RESULTS CPX caused a significant decrease in SOD activity and GSH levels, but only the latter was fully restored by morin. There were no significant differences in CAT activity in the various groups. CPX also insignificantly decreased MDA levels, which was aggravated by co-administration of morin. CONCLUSIONS The results obtained indicate that morin may exert some protective action on CPX-induced changes in the antioxidant state in rat livers.
Adrenoceptor activity of muscarinic toxins identified from mamba venoms

BACKGROUND AND PURPOSE Muscarinic toxins (MTs) are snake venom peptides named for their ability to interfere with ligand binding to muscarinic acetylcholine receptors (mAChRs). Recent data infer that these toxins may have other G‐protein‐coupled receptor targets than the mAChRs. The purpose of this study was to systematically investigate the interactions of MTs with the adrenoceptor family members.
CEO's Inside Debt and Dynamics of Capital Structure

Debt-type compensation (i.e., inside debt) exacerbates the divergence in risk preference between the CEO and shareholders that in turn affects the firm’s capital structure decisions. An excessively risk-averse CEO uses debt that falls short of the shareholders’ desired level, and is eager to lower the debt ratio when the firm is over-levered but reluctant to enhance the debt ratio when the firm is under-levered. We find that higher CEO inside debt ratio is associated with lower firm debt ratio and faster (slower) leverage adjustments toward the shareholders’ desired level for over-levered (under-levered) firms. The CEO inside debt ratio most conducive to optimal capital structure dynamics is around 10 percent of the firm’s market debt ratio.
Surgical sperm retrieval: Techniques and their indications

Men with azoospermia can father a child through intra-cytoplasmic sperm injection if sperm can be retrieved from their epididymis or testis. Several percutaneous and open surgical procedures have been described to retrieve sperm. The various techniques and their merits are discussed in this review. In men with obstructive azoospermia, epididymal sperm can usually be retrieved by percutaneous epididymal sperm aspiration (PESA). If PESA fails then testicular sperm are obtained by needle aspiration biopsy (NAB). In men with non-obstructive azoospermia, there will be no sperm in the epididymis and testicular sperm retrieval is required. Percutaneous retrieval by NAB can be tried first. If that fails then testicular sperm extraction (TESE) from open microsurgical biopsies is performed using the single seminiferous tubule (SST) or the microdissection TESE techniques. The simplest, least invasive procedure should be tried first.
The Induction of IL-10 by Zymosan in Dendritic Cells Depends on CREB Activation by the Coactivators CREB-Binding Protein and TORC2 and Autocrine PGE21

Stimulation of human monocyte-derived dendritic cells with the yeast extract zymosan is characterized by a predominant production of IL-10 and a strong induction of cyclooxygenase-2, but the molecular mechanisms underlying this response are only partially understood. To address this issue, the activation of transcription factors that may bind to the il10 proximal promoter was studied. Binding activity to Sp1, Sp3, NF-Y, and cAMP response element (CRE) sites was detected in the nuclear extracts of dendritic cells; however these binding activities were not influenced by zymosan. No binding activity to Stat1, Stat3, and c/EBP sites was detected. Notably, zymosan activated κB-binding activity, but inhibition of NF-κB was associated with enhanced IL-10 production. In sharp contrast, treatments acting on CREB (CRE binding protein), including 8-Br-cAMP, PGE2, and inhibitors of PKA, COX, and glycogen-synthase kinase-3β showed a direct correlation between CREB activation and IL-10 production. Zymosan induced binding of both P-CREB and CREB-binding protein (CBP) to the il10 promoter as judged from chromatin immunoprecipitation assays, whereas negative results were obtained with Ab reactive to Sp1, Sp3, c-Maf, and NF-Y. Zymosan also induced nuclear translocation of the CREB coactivator transducer of regulated CREB activity 2 (TORC2) and interaction of TORC2 with P-CREB coincidental with the association of CREB to the il10 promoter. Altogether, our data show that zymosan induces il10 transcription by a CRE-dependent mechanism that involves autocrine secretion of PGE2 and a network of interactions of PKA, MAP/ERK, glycogen-synthase kinase-3β, and calcineurin, which regulate CREB transcriptional activity by binding the coactivators CBP and TORC2 and inhibiting CBP interaction with other transcription factors.
Perfusion MRI and SPECT of brain after treatment for childhood acute lymphoblastic leukemia.

BACKGROUND Treatment of childhood leukemia may cause perfusion defects in the brain observed by SPECT. Perfusion MRI is a novel method to study brain perfusion which has not been used previously in this setting. This study was performed to compare SPECT with perfusion MRI in patients with acute lymphoblastic leukemia (ALL) after treatment. PROCEDURE Nineteen children or young adults underwent perfusion MRI at the cessation of treatment (n = 9) or 4-8 years after the treatment (n = 10). Seventeen of them also underwent SPECT at the time of MRI (within 0-3 days, n = 14) or a couple of months later (1.5-6 months, n = 3). SPECT images and relative cerebral blood volume (CBV) and cerebral blood flow (CBF) maps from perfusion MRI were analyzed visually. Relative CBV ratios of gray matter to white matter and thalamus to white matter were also calculated from the perfusion MRI. RESULTS Perfusion MRI did not show any focal perfusion defects, while small defects were observed by SPECT in five of 17 children (29%) in the basal, frontal or temporal areas on the left. No significant differences were observed by perfusion MRI in the relative CBV ratios in the different treatment groups. Time since treatment, age at diagnosis, brain irradiation, or findings in conventional MRI or SPECT did not have any effect on the relative perfusion values either. CONCLUSIONS SPECT may show small perfusion defects after treatment for childhood leukemia which are not visible by perfusion MRI. The clinical significance or prognosis of these defects is not known.