Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of different modeling approaches to better evaluate greenhouse gas emissions from whole wastewater treatment plants

New tools are being developed to estimate greenhouse gas (GHG) emissions from wastewater treatment plants (WWTPs). There is a trend to move from empirical factors to simple comprehensive and more complex process‐based models. Thus, the main objective of this study is to demonstrate the importance of using process‐based dynamic models to better evaluate GHG emissions. This is tackled by defining a virtual case study based on the whole plant Benchmark Simulation Model Platform No. 2 (BSM2) and estimating GHG emissions using two approaches: (1) a combination of simple comprehensive models based on empirical assumptions and (2) a more sophisticated approach, which describes the mechanistic production of nitrous oxide (N2O) in the biological reactor (ASMN) and the generation of carbon dioxide (CO2) and methane (CH4) from the Anaerobic Digestion Model 1 (ADM1). Models already presented in literature are used, but modifications compared to the previously published ASMN model have been made. Also model interfaces between the ASMN and the ADM1 models have been developed. The results show that the use of the different approaches leads to significant differences in the N2O emissions (a factor of 3) but not in the CH4 emissions (about 4%). Estimations of GHG emissions are also compared for steady‐state and dynamic simulations. Averaged values for GHG emissions obtained with steady‐state and dynamic simulations are rather similar. However, when looking at the dynamics of N2O emissions, large variability (3–6 ton CO2e day−1) is observed due to changes in the influent wastewater C/N ratio and temperature which would not be captured by a steady‐state analysis (4.4 ton CO2e day−1). Finally, this study also shows the effect of changing the anaerobic digestion volume on the total GHG emissions. Decreasing the anaerobic digester volume resulted in a slight reduction in CH4 emissions (about 5%), but significantly decreased N2O emissions in the water line (by 14%). Biotechnol. Bioeng. 2012; 109: 2854–2863. © 2012 Wiley Periodicals, Inc.
Differences in the hypothalamic-pituitary-adrenal axis of black and white men.

We previously found that, following intravenous administration of ovine corticotropin-releasing hormone (CRH), the plasma ACTH concentrations of Black women were approximately twice as high as those of White women; however, there were no corresponding differences in cortisol response. To determine whether this difference in ACTH secretion is also present in men, we studied the hypothalamic-pituitary-adrenal axis of 10 Black and 10 White weight-, age-, and education-matched men. Waist-to-hip ratio, 24-hour urine free cortisol excretion, and ACTH and cortisol responses to 1 microgram/kg ovine CRH were determined. There were no racial differences in waist-to-hip ratio, 24-hour urine free cortisol excretion, baseline free or total plasma cortisol and ACTH concentrations, or plasma cortisol response to CRH. However, CRH-stimulated plasma ACTH concentrations, measured in an extraction polyclonal radioimmunoassay, were significantly greater in Blacks than in Whites at all time points between 30 and 180 min after administration of CRH (area under curve (AUC) 1,796 +/- 245 pmol/l.min in Blacks vs. 1,278 +/- 121 pmol/l.min in Whites, p < 0.001). Neither cortisol nor ACTH AUCs were significantly correlated with Body Mass Index in Black or White men. We conclude that there are differences in the HPA axis of Black and White men similar to those found previously in women. The physiology underlying these differences remains to be understood.
Potentiation of Smad Transactivation by Jun Proteins during a Combined Treatment with Epidermal Growth Factor and Transforming Growth Factor-β in Rat Hepatocytes

Cross-talk between Smad and mitogen-activated protein kinase pathways has been described recently, and evidence for Smad cooperation with AP-1 is emerging. Here we report that epidermal growth factor (EGF) potentializes transforming growth factor β (TGF-β)−induced Smad3 transactivation in rat hepatocytes, an effect abrogated by TAM-67, a dominant negative mutant of AP-1. Antisense transfection experiments indicated that c-Jun and JunB were involved in the synergistic effect, and endogenous c-Jun physically associated with Smad3 during a combined EGF/TGF-β treatment. We next investigated which signaling pathway transduced by EGF was responsible for the Jun-induced synergism. Whereas inhibition of JNK had no effect, inhibition of the phosphatidylinositol-3′ kinase (PI3-kinase) pathway by LY294002 or by expression of a dominant negative mutant of PI3-kinase reduced EGF/TGF-β-induced Smad3 transcriptional activity. Transfection of an activated Ras with a mutation enabling the activation of the PI3-kinase pathway alone mimicked the EGF/TGF-β potentiation of Smad3 transactivation, and TAM-67 abolished this effect, suggesting that the PI3-kinase pathway stimulates Smad3 via AP-1 stimulation. The EGF/TGF-β-induced activation of Smad3 correlated with PI3-kinase and p38-dependent but not JNK-dependent phosphorylation of c-Jun. Since potentiation of a Smad-binding element-driven gene was also induced by EGF/TGF-β treatment, this novel mechanism of Jun/Smad cooperation might be crucial for diversifying TGF-β responses.
Smoking, Fasting Serum Insulin, and Obesity Are the Predictors of Carotid Atherosclerosis in Relatively Young Subjects

The purpose of this study was to identify predictors of atherosclerosis in a healthy young cohort comprised of 241 subjects who underwent a regular employee medical check-up at Ohshima National Sanatorium over a 9-month period. All subjects underwent carotid ultrasound examinations to determine maximal common carotid artery intima media thickness. In addition, serum total cholesterol, triglycerides, high-density lipoprotein cholesterol, blood urea nitrogen, creatinine, glucose, and insulin were evaluated. The subjects were relatively young (mean age, 44 years; range, 18 to 62 years), with 130 females (54%) and 111 males (46%). Maximal common carotid artery intima media thickness was predicted by smoking habit, body mass index, fasting blood sugar, fasting serum insulin, and systolic blood pressure (F5,235 = 52.8, P < 10-5). There was clear separation in common carotid artery intima media thickness values based on body mass index, smoking, and fasting serum insulin, and somewhat more overlap with systolic blood pressure and fasting blood sugar. These findings suggest that smoking and high values of body mass index, fasting serum insulin, systolic blood pressure, and fasting blood sugar are warning factors for early atherosclerosis development, and could conceivably serve as the basis of diagnostic screening. Smoking is particularly deleterious, as smokers with high body mass index, high fasting serum insulin, or high systolic blood pressure tend to have larger common carotid artery intima media thickness values than would have been predicted by consideration solely of the individual risk factors.
Molecular Epidemiology and Immunology of Hepatitis B Virus Infection – An Update

Hepatitis B virus (HBV) continues to be one of the most important viral pathogens in humans. This review provides an update on the molecular epidemiology and immunology of HBV infection. DNA sequencing has allowed replacement of the initial serotypic classification of HBV strains by a more systematic genotype system that currently consists of 7 members (genotypes A–G). More recently, sequence analysis of virus isolates from many individual patients has revealed the occurrence of certain mutational hot spots in the genome, some of which appear to correlate with the patient’s immunological and/or disease status; however, cause and effect are not always easily discernible. This holds particularly for the issue of whether virus variants exist that have, per se, an increased pathogenic potential; due to the scarcity of appropriate experimental in vivo models, such hypotheses are difficult to prove. Similarly, because of the compact organization of the HBV genome, almost every single mutation may have pleiotropic phenotypic effects. Nonetheless, there is accumulating evidence that at least some frequently observed mutations are causally related to viral escape from selective pressures, such as the presence of antibodies against dominant B cell epitopes, or drugs that inhibit the viral reverse transcriptase; possibly, this is also true for the cellular immune response. Therefore, despite the availability of an effective prophylactic vaccine, further extensive efforts are required to monitor the emergence of vaccination- and therapy-resistant HBV variants and to prevent their spread in the general population.
Recombinant methionyl human leptin therapy in replacement doses improves insulin resistance and metabolic profile in patients with lipoatrophy and metabolic syndrome induced by the highly active antiretroviral therapy.

CONTEXT Highly active antiretroviral therapy (HAART) for HIV-1 infection has been associated with a metabolic syndrome characterized by insulin resistance, hyperlipidemia, and redistribution of body fat (lipodystrophy). A subset of patients with predominant lipoatrophy has low levels of the adipocyte-secreted hormone leptin. OBJECTIVE The objective of the study was to assess whether administration of recombinant methionyl human leptin (r-metHuLeptin) improves insulin resistance and other metabolic abnormalities in HIV+ leptin-deficient subjects with HAART-induced lipoatrophy. DESIGN, SETTING, PATIENTS, AND INTERVENTION We conducted a randomized, placebo-controlled, double-blinded, crossover study from 2002 to 2004 in seven HIV+ men with HAART-induced lipoatrophy, serum leptin level less than 3 ng/ml, and fasting triglyceride level greater than 300 mg/dl, who were administered placebo for 2 months before or after administration of r-metHuLeptin at physiological doses for an additional 2 months. MAIN OUTCOME MEASURES Insulin resistance, lipid levels, inflammatory markers, body composition, and HIV control were measured. RESULTS Compared with placebo, r-metHuLeptin therapy improved fasting insulin levels, insulin resistance (as expressed by the homeostasis model assessment index and an insulin suppression test), and high-density lipoprotein. Body weight and fat mass decreased on r-metHuLeptin, mainly due to a decrease in truncal fat but not peripheral fat or lean body mass. r-metHuLeptin was well tolerated, and HIV control was not adversely affected. CONCLUSIONS r-metHuLeptin replacement at physiological doses in HIV+ leptin-deficient patients with HAART-induced lipoatrophy improves insulin resistance, high-density lipoprotein, and truncal fat mass. Future larger and more long-term studies in HAART-induced lipoatrophy, including patients with more severe metabolic abnormalities, are warranted to evaluate the physiological and potentially therapeutic role of r-metHuLeptin for this condition and to fully clarify the underlying mechanisms of action.
Neurourology and Urodynamics 35 : 551 – 563 ( 2016 ) A Guideline for the Management of Bladder Dysfunction in Parkinson ’ s Disease and Other Gait Disorders

Ryuji Sakakibara,* Jalesh Panicker, Enrico Finazzi-Agro, Valerio Iacovelli, Homero Bruschini, and The Parkinson’s Disease Subcomittee, The Neurourology Promotion Committee in The International Continence Society Neurology, Internal Medicine, Sakura Medical Center, Toho University, Sakura, Japan Neurology, National Hospital for Neurology & Neurosurgery, London, United Kingdom Department of Experimental Medicine and Surgery, Tor Vergata University and Unit for Functional Urology, Policlinico Tor Vergata University Hospital, Rome, Italy School of Specialization in Urology, Tor Vergata University Unit for Functional Urology, Policlinico Tor Vergata University Hospital, Rome, Italy Urology, University of Sao Paulo, Brazil
The cost burden of trastuzumab and bevacizumab monoclonal antibody therapy in solid tumors: Can we afford it?

6044 Background: Monoclonal antibodies (MAb), such as trastuzumab (TZ) and bevacizumab (BZ), have become an important yet expensive component of cancer treatment. The potential cost impact on health care budgets needs to be assessed in the context of its potential utilization. An estimate of the additional costs incurred by adopting TZ and BZ therapy in breast (BRC), lung (LUC) and colorectal (CRC) cancers was undertaken. METHODS The MAb costs per patient were estimated based on treatment indications, length of treatment, standard doses / schedules and local pharmacy data. Supportive medications, diagnostics and health resources utilization only required for the MAb therapy were also examined. This analysis was performed in Canadian dollars ($), and assumes complete drug delivery and uncomplicated cycles. Drug costs were based on average 2005 wholesale prices in Canada. The analysis took a direct payer perspective. We subsequently estimated the cost of MAb therapy per patient relative to the total costs of conventional cancer management without MAb therapy. Budget impact estimates on Canada's health care system were then derived according to constructed schema, which accounts for absolute numbers of target patients and systemic therapy utilization. RESULTS The average costs of TZ per treated patient were $47,278 and $26,648 for adjuvant and metastatic BRC, respectively. For BZ, these were $47,250 and $38,500 for metastatic LUC and CRC, respectively. Other costs associated with MAb therapy were in the range of 3-6%. The predicted TZ drug costs in metastatic breast cancer were within 10% of the actual costs derived from pharmacy data. The potential life-time absolute costs to Canada's health care system were approximately $118 million for TZ, and $262 million for BZ. This corresponds to an average of approximately 21% increase in the health care expenditure for BRC, LUC, and CRC. CONCLUSIONS MAb therapy, such as TZ and BZ, may add a significant cost burden to Canada's publicly funded health care system. The developed schema in this analysis may be of potential use to health care providers and policy makers in assessing the impact of MAb therapy on health care budgets. No significant financial relationships to disclose.
Major Depressive Disorder in Taiwan Defined by the Chinese Diagnostic Interview Schedule

The lifetime prevalence rate of major depressive disorder (MDD), as defined by the Chinese Diagnostic Interview Schedule, is 1.14% in Taiwan. This is significantly lower than the lifetime prevalence rates reported in Western studies and similar to other studies in the Chinese population using similar methods for assessing cases of MDD. Epidemiological data from 136 MDD cases were analyzed to provide possible explanations for this difference in lifetime prevalence rates. The low rate of broken families in Chinese culture, low comorbidity rate, and older age of onset of MDD may suggest a reality of low lifetime prevalence rates of MDD in Taiwan.
Rv1698 of Mycobacterium tuberculosis Represents a New Class of Channel-forming Outer Membrane Proteins*

Mycobacteria contain an outer membrane composed of mycolic acids and a large variety of other lipids. Its protective function is an essential virulence factor of Mycobacterium tuberculosis. Only OmpA, which has numerous homologs in Gram-negative bacteria, is known to form channels in the outer membrane of M. tuberculosis so far. Rv1698 was predicted to be an outer membrane protein of unknown function. Expression of rv1698 restored the sensitivity to ampicillin and chloramphenicol of a Mycobacterium smegmatis mutant lacking the main porin MspA. Uptake experiments showed that Rv1698 partially complemented the permeability defect of the M. smegmatis porin mutant for glucose. These results indicated that Rv1698 provides an unspecific pore that can partially substitute for MspA. Lipid bilayer experiments demonstrated that purified Rv1698 is an integral membrane protein that indeed produces channels. The main single channel conductance is 4.5 ± 0.3 nanosiemens in 1 m KCl. Zero current potential measurements revealed a weak preference for cations. Whole cell digestion of recombinant M. smegmatis with proteinase K showed that Rv1698 is surface-accessible. Taken together, these experiments demonstrated that Rv1698 is a channel protein that is likely involved in transport processes across the outer membrane of M. tuberculosis. Rv1698 has single homologs of unknown functions in Corynebacterineae and thus represents the first member of a new class of channel proteins specific for mycolic acid-containing outer membranes.
Complexity and "chaos" in blood pressure after baroreceptor denervation of conscious dogs.

To investigate how arterial baroreceptors affect the dynamic properties of short-term blood pressure control, we determined Lyapunov exponents and correlation dimensions of blood pressure. Two groups of conscious dogs were studied: a control group (n = 7) and a group subjected to total sinoaortic and cardiopulmonary baroreceptor denervation (n = 7). As a measure of variability, standard deviation was determined and power spectra were calculated. In the lower frequency range (f < 0.1 Hz) power density was inversely related to frequency in both groups, indicating "1/f noise. " Estimating the correlation dimension via the Grassberger-Procaccia algorithm as a quantification of complexity revealed a decrease after baroreceptor denervation (1.74 +/- 0.2 vs. 3.05 +/- 0.23 control; P < 0.05). Determination of the largest Lyapunov exponents lambda 1, which indicates the sensitive dependence on initial conditions, a hallmark of chaos, also yielded a diminution after denervation (lambda 1 = 0.74 +/- 0.08 vs. 1.85 +/- 0.18, P < 0.01). The results were cross-checked with surrogate data statistics. The null hypothesis, that there is no nonlinear structure in arterial blood pressure time series, was rejected. This shows that after baroreceptor denervation, blood pressure control is less complex and less sensitive to initial conditions ("chaos"). In contrast, variability (standard deviation) is increased (22.2 +/- 3.1 denervation vs. 8.3 +/- 1.4 control; P < 0.05). It is concluded that under physiological conditions, arterial and cardiopulmonary baroreceptors reduce variability of blood pressure, however, at the cost of blood pressure being less predictable. Thus the regulation is more sensitive depending on initial conditions. (ABSTRACT TRUNCATED AT 250 WORDS)
Reconciling the definitions of polycystic ovary syndrome: the ovarian follicle number and serum anti-Müllerian hormone concentrations aggregate with the markers of hyperandrogenism.

CONTEXT It is still debated whether clinical and/or biological indices of hyperandrogenism (HA) should be present to qualify a patient as having polycystic ovary syndrome (PCOS). We hypothesized that excessive follicle number (FN) assessed by ovarian ultrasonography and/or serum anti-Müllerian hormone (AMH) concentrations may be used as surrogates for the classical markers of HA. DESIGN AND METHODS Data were obtained from a database of clinical, hormonal, and ultrasound features that were consecutively recorded in 270 women with PCOS (defined using the Rotterdam Criteria) and 217 infertile nonhyperandrogenic normoovulatory women. These variables were submitted to principal component analysis, a multivariable statistical procedure that transforms a number of possibly correlated variables into a smaller number of uncorrelated variables called principal components (PC). Variables that aggregate in the same PC capture the same information. RESULTS In the control group, as expected, three independent PCs were identified: 1) the markers of the metabolic (i.e. insulin resistance) status; 2) those of the androgen status; and 3) those of the follicle status. In the PCOS group, the metabolic variables also aggregated in a first PC. Ovarian androgen and follicle markers aggregated in a second independent PC, with FN and serum AMH having the strongest correlation coefficients. A third PC summarized the adrenal contribution to the HA of PCOS. In both groups, the free androgen index correlated equally to the first and second PCs. CONCLUSIONS The similarity of the first PC between controls and PCOS supports the hypothesis that the metabolic anomaly of PCOS is neither intrinsic nor specific. Conversely, by gathering the androgen and follicle variables, the second PC in PCOS may be viewed as summarizing a specific ovarian anomaly. Because both FN and/or serum AMH were strongly correlated to the second PC along with androgens, they may be used equally as surrogates for the classical markers of ovarian HA. This reconciles the Rotterdam Consensus and other definitions for PCOS, especially in women having the Rotterdam PCOS phenotype without HA. We thus propose a simple strategy for the diagnosis of PCOS in clinical practice.
Acute Rejection Rates and Graft Outcomes According to Induction Regimen among Recipients of Kidneys from Deceased Donors Treated with Tacrolimus and Mycophenolate.

BACKGROUND AND OBJECTIVES IL-2 receptor antagonist (IL2-RA) is recommended as a first-line agent for induction therapy in renal transplantation. However, this remains controversial in deceased donor renal transplantation (DDRT) maintained on tacrolimus (TAC)/mycophenolic acid (MPA) with or without steroids. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We studied the United Network for Organ Sharing Registry for patients receiving DDRT from 2000 to 2012 maintained on TAC/MPA at transplantation hospital discharge (n=74,627) to compare outcomes of IL2-RA and other induction agents. We initially divided the cohort into two groups on the basis of steroid use at the time of discharge: steroid (n=59,010) versus no steroid (n=15,617). Each group was stratified into induction categories: IL2-RA, rabbit antithymocyte globulin (r-ATG), alemtuzumab, and no induction. The main outcomes were incidence of acute rejection within the first year and overall graft failure (defined as graft failure and/or death) post-transplantation. Propensity score (PS), specifically inverse probability of treatment weight, analysis was used to minimize selection bias caused by nonrandom assignment of induction therapies. RESULTS Median (25th, 75th percentiles) follow-up times were 3.9 (1.1, 5.9) and 3.2 (1.1, 4.9) years for steroid and no steroid groups, respectively. Acute rejection within the first year and overall graft failure within 5 years of transplantation were more common in the no induction category (13.3%; P<0.001 and 28%; P=0.01, respectively) in the steroid group and the IL2-RA category (11.1%; P=0.16 and 27.4%; P<0.001, respectively) in the no steroid group. Compared with IL2-RA, PS-weighted and covariate-adjusted multivariable logistic and Cox analyses showed that outcomes in the steroid group were similar among induction categories, except that acute rejection was significantly lower with r-ATG (odds ratio [OR], 0.68; 95% confidence interval [95% CI], 0.62 to 0.74). In the no steroid group, compared with IL2-RA, odds of acute rejection with r-ATG (OR, 0.80; 95% CI, 0.60 to 1.00) and alemtuzumab (OR, 0.68; 95% CI, 0.53 to 0.88) were lower, and r-ATG was associated with better graft survival (hazard ratio, 0.86; 95% CI, 0.75 to 0.99). CONCLUSIONS In DDRT, compared with IL2-RA induction, no induction was associated with similar outcomes when TAC/MPA/steroids were used. r-ATG seems to offer better graft survival over IL2-RA in steroid avoidance protocols.