Miracle-dz/UniFAR-FTUs huggingface dataset:
Survey of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans and non-ortho-polychlorinated biphenyls in US meat and poultry, 2012–13: toxic equivalency levels, patterns, temporal trends and implications

ABSTRACT The US Department of Agriculture (USDA) conducts a statistically based survey of the domestic meat supply (beef, pork, chicken and turkey) to determine current levels of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and non-ortho-polychlorinated biphenyls (no-PCBs) every 5 years. Fat samples for each slaughter class were collected from US federally licensed slaughter facilities. The samples were processed and analysed for 17 PCDD/Fs and three no-PCBs. The sum of PCDD, PCDF and no-PCB toxic equivalencies (sum-TEQ) calculated using 2005 toxic-equivalency factors for all slaughter classes ranged from non-detect (n.d.) to 6.47 pg TEQ g–1 lipid. The median sum-TEQs, when n.d. = 0.5 LOD, for beef, pork, chicken and turkey were 0.66, 0.12, 0.13 and 0.34 pg TEQ g–1 lipid respectively. A comparison of the current survey with the previous three surveys shows a declining trend, with decreasing differences between medians; differences between the median sum-TEQs from 2007–08 and 2012–13 were –10%, –29%, –33% and –25% for beef, pork, chicken and turkey respectively. Several beef samples underwent further characterisation and congener patterns from these beef samples suggested pentachlorophenol treated wood as the likely exposure source. US consumer exposure to these compounds is relatively low and no slaughter class contributed more than 26% to the US Environmental Protection Agency (USEPA) chronic oral reference dose of 0.7 pg TEQ kg–1 bw day–1. Graphical Abstract
The relative clinical efficacy of trametinib–dabrafenib and cobimetinib–vemurafenib in advanced melanoma: an indirect comparison

Melanoma causes the majority of skin cancer‐related deaths. The outcome of melanoma depends on its stage at diagnosis. Currently, for patients with advanced melanoma, two MEK inhibitors (trametinib and cobimetinib) have been authorized by the European Medicines Agency. The main objective of this study was to compare the relative efficacy of trametinib–dabrafenib and cobimetinib–vemurafenib in patients with advanced melanoma through adjusted indirect treatment comparisons (ITCs).
[Effect of Huangqi injection on short-term prognosis in children with acute lymphoblastic leukemia].

OBJECTIVE To investigate the effect of Huangqi injection on the short-term prognosis in childhood with acute lymphoblastic leukemia (ALL). METHODS A retrospective analysis was performed on the clinical data of 105 children newly diagnosed with ALL between January 2009 and December 2012. These children were randomly divided into treatment group (18 low-risk cases, 7 medium-risk cases, and 24 high-risk cases) and control group (21 low-risk cases, 7 medium-risk cases, 28 high-risk cases). Both groups were given remission induction therapy based on the levels of risk. Throughout the remission induction therapy, the treatment group also received Huangqi injection (0.5-1.0 mL/kg per day) by intravenous infusion, while the control group was given 0.9% sodium chloride injection instead. The two groups were compared in terms of distribution of prognostic factors and complete remission (CR) rate after remission induction therapy, as well as the incidence of minimal residual disease (MDR) (≥ 10(-4) and < 10(-4)) among all patients in the two groups on day 19 of remission induction therapy and among B-ALL patients in the two groups when achieving a CR at the end of remission induction therapy. RESULTS Of the 105 children with ALL, 99 had B-ALL, and 6 had T-ALL. There were no significant differences in the distribution of prognostic factors between the two groups (P>0.05). The overall CR rate of 105 patients was 79%; there was no significant difference in CR rate between the treatment and control groups (82% vs 77%; P>0.05); also, no significant differences were found between the two groups in the CR rates among high-, medium-, and low-risk cases (P>0.05). On day 19 of remission induction therapy, the incidence of MRD≥10(-4) in the treatment group was significantly lower than that in the control group (69% vs 95%; P<0.05); among 80 children with B-ALL who achieved a CR (43 cases in the control group and 37 cases in the treatment group), the incidence of MRD≥10-4 was significantly lower in the treatment group than in the control group (27% vs 58%; P<0.05); in both circumstances above, the high- and low-risk cases in the treatment group had a significantly lower incidence of MRD≥10(-4) than the control group (P<0.05). CONCLUSIONS Huangqi injection combined with chemotherapy has an enhanced anti-tumor effect and can improve the short-term prognosis and clinical outcome in children with ALL.
Androgen insensitivity.

The androgen receptor (AR) protein regulates transcription of certain genes. Usually, this activity depends upon a central DNA-binding domain that permits the binding of androgen-AR complexes to regulatory DNA sequences near or in a target gene. The AR also has a C-terminal androgen-binding domain (ABD) and an N-terminal modulatory domain. These domains interact among themselves and with coregulatory, nonreceptor proteins to determine vector control over a gene's transcription rate. The precise roles of these proteins are active research areas. Severe X-linked androgen receptor gene (AR) mutations cause complete androgen insensitivity, mild ones impair virilization with or without infertility, and moderate ones sometimes yield a wide phenotypic spectrum among sibs. Different expressivity may reflect variability of AR-interactive proteins. The family history must identify heterozygous XX females with sparse, delayed, or asymmetric pubic/axillary hair or delayed menarche and infertile XY maternal aunts or uncles. Mutation type and density vary along the length of the AR. N-terminal polyglutamine tract expansion limits AR transactivation, causing a form of mild androgen insensitivity. Analysis of ABD mutations that do not impair androgen binding or impair it selectively will illuminate its intradomain properties. For partial androgen insensitivity and mild androgen insensitivity, pharmacotherapy with certain androgens or other steroids may overcome some dysfunction of certain mutant ARs. Experience with this approach is limited; outcomes have been generally disappointing.
REST4-mediated modulation of REST/NRSF-silencing function during BDNF gene promoter activation.

Neural-restrictive silencer element (NRSE)/repressor element-1 (RE1) regulates neuron-specific gene expression by binding the transcriptional factor REST/NRSF which functions as a silencer in nonneuronal cells. In neuronal cells, a truncated, neuronal-specific REST/NRSF isoform, REST4, has been found but little is known about its function. To address this, we investigated the effect of REST/NRSF and REST4 on the activity-dependent activation of BDNF gene promoter I (BDNFp-I) using cultured rat cortical neurons. REST/NRSF markedly repressed the transcriptional activation of BDNFp-I, whereas the effect of REST4 was weak, depending upon the NRSE/RE1 sequence. In addition, REST4 enhanced the basal transcriptional activity of BDNFp-I. Coexpression of REST4 with REST/NRSF competitively inhibited the silencing effect of REST/NRSF on the activation of BDNFp-I. Although REST4 itself has a weak repressive effect on activation of the BDNF gene via NRSE/RE1, it can compete the silencing effect of REST/NRSF, suggesting a primary role for REST4 in preventing the neuron-specific gene from being inactivated by REST/NRSF and allowing gene activation in response to a variety of neuronal stimuli.
Comparative Genomic Analysis of Haemophilus haemolyticus and Nontypeable Haemophilus influenzae and a New Testing Scheme for Their Discrimination

ABSTRACT Haemophilus haemolyticus has been recently discovered to have the potential to cause invasive disease. It is closely related to nontypeable Haemophilus influenzae (NT H. influenzae). NT H. influenzae and H. haemolyticus are often misidentified because none of the existing tests targeting the known phenotypes of H. haemolyticus are able to specifically identify H. haemolyticus. Through comparative genomic analysis of H. haemolyticus and NT H. influenzae, we identified genes unique to H. haemolyticus that can be used as targets for the identification of H. haemolyticus. A real-time PCR targeting purT (encoding phosphoribosylglycinamide formyltransferase 2 in the purine synthesis pathway) was developed and evaluated. The lower limit of detection was 40 genomes/PCR; the sensitivity and specificity in detecting H. haemolyticus were 98.9% and 97%, respectively. To improve the discrimination of H. haemolyticus and NT H. influenzae, a testing scheme combining two targets (H. haemolyticus purT and H. influenzae hpd, encoding protein D lipoprotein) was also evaluated and showed 96.7% sensitivity and 98.2% specificity for the identification of H. haemolyticus and 92.8% sensitivity and 100% specificity for the identification of H. influenzae, respectively. The dual-target testing scheme can be used for the diagnosis and surveillance of infection and disease caused by H. haemolyticus and NT H. influenzae.
Evaluation of the Health Promotion Model to Predict Physical Activity in Iranian Adolescent Boys

Promoting sustainable physical activity (PA) behavior change is challenging, and a number of theoretical models have been developed and applied to this problem. Pender’s health promotion model (HPM) is a relatively new model that is based on Bandura’s social cognitive theory but includes the additional construct of competing demands, which are viewed as alternative behaviors (e.g., watching television) that have powerful reinforcing properties. This study evaluates the HPM as a means to predict PA in a sample of Iranian adolescent boys. Participants were 515 boys from 100 junior high and high schools in Sanandaj, Iran. Participants’ mean age was 14.33 years (SD = 1.6, range = 12-17). Participants completed questions assessing social cognitive variables, and structural equation modeling was used to fit the data to the HPM. The HPM accounted for 37% of the variance in PA but did not represent a good data fit (χ2 = 913.85, df = 473, p < .001). There were significant pathways between PA and self-efficacy (β = .25, p < .001), enjoyment (β = .22, p < .01), and PA modeling (β = —.13, p < .05). A revised model that included the indirect effects of competing demands explained 34% of the variance in PA and represented a good data fit (χ 2 = 9.12, df = 4, p = .058). In the revised model, self-efficacy, commitment to planning, and enjoyment were associated with PA. According to the HPM, competing demands influence PA. In the study sample, competing demands were not related to PA but were inversely associated with commitment to planning.
Trade Performance of Export Processing Zones

Export processing zones (EPZs) have become widespread with the liberalisation of international trade and investment. They are key players in the deepening of the global value chain (GVC). However, little is known about their contribution to world trade due to a lack of information on their location and status. This paper sets out to improve knowledge in this area by analysing the trade performance of EPZ countries at macro-level with a focus on EPZ externalities and distortive costs. We have built an original database of EPZs in which we define them as processing zones benefiting from import tariff incentives. We show that EPZs increase trade only by easing the negative impact of protection. As importers of components and raw materials, they raise the rest of the world's exports. This confirms the contribution of EPZs to the GVC. This result is robust to a change in the model specification, errors and bias due to data collection issues and sample composition.
The hidden curriculum, ethics teaching, and the structure of medical education

The authors raise questions regarding the wide-spread calls emanating from lay and medical audiences alike to intensify the formal teaching of ethics within the medical school curriculum. In particular, they challenge a prevailing belief within the culture of medicine that while it may be possible to teach information about ethics (e.g., skills in recognizing the presence of common ethical problems, skills in ethical reasoning, or improved understanding of the language and concepts of ethics), course material or even an entire curriculum can in no way decisively influence a student's personality or ensure ethical conduct. To this end, several issues are explored, including whether medical ethics is best framed as a body of knowledge and skills or as part of one's professional identity. The authors argue that most of the critical determinants of physician identity operate not within the formal curriculum but in a more subtle, less officially recognized “hidden curriculum. ” The overall process of medical education is presented as a form of moral training of which formal instruction in ethics constitutes only one small piece. Finally, the authors maintain that any attempt to develop a comprehensive ethics curriculum must acknowledge the broader cultural milieu within which that curriculum must function. In conclusion, they offer recommendations on how an ethics curriculum might be more fruitfully structured to become a seamless part of the training process.
The (pro)renin receptor: pathophysiological roles in cardiovascular and renal pathology

Purpose of reviewThe pathophysiological role of the (pro)renin receptor is yet to be established. The present review summarizes the findings, suggesting that it may play pathological role in cardiac and renal fibrosis, and in hypertensive and diabetic nephropathy. Recent findingsIn-vitro and animal studies have shown that increased receptor expression could be linked to high blood pressure and to cardiac and glomerular fibrosis by activating mitogen-activated protein kinases and by upregulating gene expression of profibrotic molecules. Studies also suggest that the receptor is involved in diabetic nephropathy by activating receptor-bound prorenin, thereby increasing angiotensin II tissue generation. Moreover, in diabetic mice, a peptide able to block prorenin binding to the receptor was claimed to be more effective for renal protection than angiotensin-converting enzyme inhibitor. SummaryThe experimental data confirmed the pivotal role of the receptor in cell surface generation of angiotensin and suggested its potential role in tissue fibrosis via receptor activation and intracellular signaling. The data also questioned the ability of soon available renin inhibitors to inhibit the activity of receptor-bound renin and prorenin, and the benefit of a new class of drug – (pro)renin receptor blockers – to prevent tissue damage.
The Complexity Landscape of Fixed-Parameter Directed Steiner Network Problems

Given a directed graph G and a list (s1, t1), …, (sd, td) of terminal pairs, the Directed Steiner Network problem asks for a minimum-cost subgraph of G that contains a directed si → ti path for every 1≤ i ≤ d. The special case Directed Steiner Tree (when we ask for paths from a root r to terminals t1, …, td) is known to be fixed-parameter tractable parameterized by the number of terminals, while the special case Strongly Connected Steiner Subgraph (when we ask for a path from every ti to every other tj) is known to be W[1]-hard parameterized by the number of terminals. We systematically explore the complexity landscape of directed Steiner problems to fully understand which other special cases are FPT or W[1]-hard. Formally, if ℋ is a class of directed graphs, then we look at the special case of Directed Steiner Network where the list (s1, t1), …, (sd, td) of demands form a directed graph that is a member of ℋ. Our main result is a complete characterization of the classes ℋ resulting in fixed-parameter tractable special cases: we show that if every pattern in ℋ has the combinatorial property of being “transitively equivalent to a bounded-length caterpillar with a bounded number of extra edges,” then the problem is FPT, and it is W[1]-hard for every recursively enumerable ℋ not having this property. This complete dichotomy unifies and generalizes the known results showing that Directed Steiner Tree is FPT [Dreyfus and Wagner, Networks 1971], q-Root Steiner Tree is FPT for constant q [Suchý, WG 2016], Strongly Connected Steiner Subgraph is W[1]-hard [Guo et al., SIAM J. Discrete Math. 2011], and Directed Steiner Network is solvable in polynomial-time for constant number of terminals [Feldman and Ruhl, SIAM J. Comput. 2006], and moreover reveals a large continent of tractable cases that were not known before.
Comparison of Endovenous Laser and Radiofrequency Ablation in Treating Varicose Veins in the Same Patient

Purpose: To compare endovenous laser ablation (EVLA) and radiofrequency venous ablation (RFA) in different legs in the same patients with venous insufficiency. Methods: Sixty patients with bilateral saphenous vein insufficiency were included. Endovenous laser ablation or RFA was applied to one of the patient’s legs and the remaining procedure, RFA or EVLA, to the other leg. Results: Minor complications in EVLA and RFA were hyperemia at 20.7% and 31.0%, ecchymosis at 31.0% and 51.7% and edema at 27.6% and 65.5%, respectively. The rate of recanalization was 6.8% in the RFA group. No recanalization was observed in the EVLA group. The level of patients satisfied with EVLA was 51.7%, compared to 31.0% for RFA, while 17.2% of patients were satisfied with both the procedures. Times to return to daily activity were 0.9 days in the EVLA group and 1.3 days in the RFA group. Conclusion: The EVLA procedure may be superior to RFA in certain respects.
Direct Cost Analyses of Palivizumab Treatment in a Cohort of At-Risk Children: Evidence From the North Carolina Medicaid Program

Objective. Use of palivizumab prophylactic therapy reduces the occurrence of hospitalizations for serious respiratory syncytial virus (RSV) lower respiratory tract infections in at-risk infants. The direct cost-benefit of palivizumab prophylaxis for infants who are born at 32 to 35 weeks' estimated gestational age (EGA) during their first year of life has not been systematically examined. The objective of this study was to compare the direct costs of palivizumab prophylaxis and RSV treatment in infants who were born at 32 to 35 weeks EGA and received and did not receive palivizumab. Methods. A cohort study was performed of infants who were younger than 1 year and were enrolled in an enhanced primary care case management model within the North Carolina Medicaid Program. Comparisons were made between infants who received (Synagis prophylaxis group) and did not receive palivizumab (nonprophylaxis group) during the study period. Cost was examined using the sum of Medicaid paid services for prophylaxis with palivizumab and treatment for RSV infections that occurred between October 1, 2002, and May 31, 2003. The Anderson framework was used to specify the regression cost models to compare the participants who received (Synagis prophylaxis) and did not receive (nonprophylaxis group) palivizumab. The primary outcomes were actual 7-month seasonal costs and standardized seasonal costs adjusting for the varied months of infant participation. Results. The study sample included 185 Synagis prophylaxis and 182 nonprophylaxis participants who met the inclusion criteria. The average per-person total cost of RSV care and prophylaxis was $5117 for the Synagis prophylaxis group and $371 for the nonprophylaxis group. Five hospitalizations occurred in the prophylaxis group, and 12 occurred in the nonprophylaxis group (odds ratio: 0.27). No deaths occurred in either group. Conclusions. Palivizumab administered to infants who were born at 32 to 35 weeks' EGA did not provide direct cost savings related to hospitalization or ambulatory care in a Medicaid population. The primary difference in cost between the groups was attributable to the palivizumab prophylaxis.
Influence of diabetes mellitus on clinical outcomes across the spectrum of acute coronary syndromes. Findings from the GUSTO-IIb study. GUSTO IIb Investigators.

AIMS We examined the characteristics, outcomes, and effects of hirudin vs heparin treatment of diabetic patients across the spectrum of acute coronary syndromes. METHODS AND RESULTS We studied the 12,142 patients enrolled in the randomized GUSTO-IIb study. Diabetic patients (n=2175) were older, more often female, more often had prior cardiovascular disease, hypertension, and hyperlipidaemia, and less often were current smokers. Diabetic patients had a higher overall incidence of death or (re)infarction at 30 days (13.1% vs 8.5%, P=0.0001), whether they presented with ST-segment elevation (13.9% vs 9.9%, P=0.0017) or not (12.8% vs 7.8%, P=0.0001), and at 6 months (18.8% vs 11.4%, P=0.0001). Among diabetic patients, hirudin was associated with a tendency toward a lower risk of death or (re)infarction at 30 days (12.2% vs 13.9% with heparin) and 6 months (17.8% vs 20.2%). Diabetic patients had more major bleeding, stroke, heart failure, shock, atrioventricular block, and atrial arrhythmias, but no increased risk for ocular bleeding. CONCLUSIONS Diabetic patients with acute coronary syndromes had worse 30-day and 6-month outcomes, particularly those without ST-segment elevation. The statistically non-significant trend toward improved outcomes with hirudin was similar among patients with and without diabetes, with a greater point estimate for the absolute difference in patients with diabetes.
Status Seeking and Nonrenewable Resource Use

Concern for social status generates an excess level of consumption at the cost of natural resource deple- tion. The excessive use of nonrenewable resources may be especially problematic in view of their irreversible nature. Despite this, no studies investigate the effect of status seeking on the time path of extraction of nonre- newable resources. This paper analyzes how status seeking affects the long-run extraction of nonrenewables in a competitive economy based on Hotelling's rule. The analysis shows that the elasticity of the marginal utility of normal goods is an important factor in determining trends in the rate of wasteful use of nonrenewable resourc- es. We also discuss the effects of improvements in resource intensity on nonrenewable resource use.
Anti-salusin-β antibody enhances angiogenesis after myocardial ischemia reperfusion injury

Backgrounds: Salusins are multifunctional endogenous bioactive peptides simultaneously biosynthesized from their precursor prosalusin. Salusin-β stimulates proliferation of vascular smooth muscle cells and fibroblasts and regulates myocardial growth and hypertrophy. Salusin-β has potent hypotensive, bradycardic and proatherosclerotic effects. Objectives: To investigate whether salusin-β plays a role in myocardial remodeling after myocardial ischemia reperfusion (I/R) injury, rat I/R models were created by the left anterior descending coronary artery occlusion for 30 min, followed by 24 h or 7 days of reperfusion (control, n = 6 each). Results and Conclusion: Immunohistochemical double staining showed the enhanced expression of salusin-β in the macrophages around myocardial ischemic area. Anti-salusin-β treated groups were administered the neutralizing salusin-β antibody (10 μl/day, i.p.) once daily from day −1 to day 1 or from day −1 to day 7 (anti-salusin-β, n = 6 each). The anti-salusin-β therapy enhanced myocardial angiogenesis in the peri-ischemic area of reperfusion. The small vessels (< 40 μm in diameter) of I/R hearts treated with anti-salusin-β were more densely populated than those of control animals (108.5 ± 19.7 vs 47.5 ± 2.4, p < 0.05). Real-time PCR revealed that the anti-salusin-β therapy-induced angiogenesis was not associated with enhanced vascular endothelial growth factor A expression. The authors, for the first time, have clarified that endogenous salusin-β suppresses angiogenesis which is critical in the development of cardiac remodeling following I/R injury.