Miracle-dz/UniFAR-FTUs huggingface dataset:
Improved primary immunodiagnosis of alveolar echinococcosis in humans by an enzyme-linked immunosorbent assay using the Em2plus antigen

Alveolar echinococcosis (AE) in humans is generally a fatal disease when not diagnosed early enough to provide curative treatment such as radical surgery. Immunodiagnosis for early detection of AE was improved by the isolation of an affinity-purified metacestode Em2 antigen and by the synthesis of recombinant Echinococcus multilocularis antigen II/3-10. Both antigens were individually assessed by enzyme-linked immunosorbent assay (ELISA) and demonstrated high specificities and diagnostic sensitivities, although both missed approximately 4 to 11% of diagnostic cases of AE. To provide an optimal serodiagnostic test, we investigated the two purified antigens by using a test employing a mixture of both purified antigens (designated Em2plus antigen) in one assay. For comparative purposes, crude E. multilocularis and Echinococcus granulosus metacestode antigens were investigated as well. The Em2plus ELISA proved to be the optimal diagnostic test with the highest diagnostic sensitivity, 97%, in serum samples from 140 patients with AE and an overall specificity of 99% for infections due to other Echinococcus and non-Echinococcus parasites. The new test combination (Em2plus ELISA) is suggested for the serodiagnosis of AE in patients and for seroepidemiological surveys.
Overexpression of HSF2-β Inhibits Hemin-induced Heat Shock Gene Expression and Erythroid Differentiation in K562 Cells*

Acquisition of heat shock factor 2 (HSF2) DNA binding activity is accompanied by induced transcription of heat shock genes in hemin-treated K562 cells undergoing erythroid differentiation. Previous studies revealed that HSF2 consists of two alternatively spliced isoforms, HSF2-α and HSF2-β, whose relative abundance is developmentally regulated and varies between different tissues. To investigate whether the molar ratio of HSF2-α and HSF2-β isoforms is crucial for the activation of HSF2 and whether the HSF2 isoforms play functionally distinct roles during the hemin-mediated erythroid differentiation, we generated cell clones expressing different levels of HSF2-α and HSF2-β. We show that in parental K562 cells, the HSF2-α isoform is predominantly expressed and HSF2 can be activated upon hemin treatment. In contrast, when HSF2-β is expressed at levels exceeding those of endogenous HSF2-α, the hemin-induced DNA binding activity and transcription of heat shock genes are repressed, whereas overexpression of HSF2-α results in an enhanced hemin response. Furthermore, the hemin-induced accumulation of globin, known as a marker of erythroid differentiation, is decreased in cells overexpressing HSF2-β. We suggest that HSF2-β acts as a negative regulator of HSF2 activity during hemin-mediated erythroid differentiation of K562 cells.
Ontogeny-related pharmacogene changes in the pediatric liver transcriptome

Objectives The majority of drug dosing studies are based on adult populations, with modification of the dosing for children based on size and weight. This rudimentary approach for drug dosing children is limited, as biologically a child can differ from an adult in far more aspects than just size and weight. Specifically, understanding the ontogeny of childhood liver development is critical in dosing drugs that are metabolized through the liver, as the rate of metabolism determines the duration and intensity of a drug’s pharmacologic action. Therefore, we set out to determine pharmacogenes that change over childhood development, followed by a secondary agnostic analysis, assessing changes transcriptome wide. Materials and methods A total of 47 human liver tissue samples, with between 10 and 13 samples in four age groups spanning childhood development, underwent pair-end sequencing. Kruskal–Wallis and Spearman’s rank correlation tests were used to determine the association of gene expression levels with age. Gene set analysis based on the pathways in KEGG utilized the gamma method. Correction for multiple testing was completed using q-values. Results We found evidence for increased expression of ‘very important pharmacogenes’, for example, coagulation factor V (F5) (P=6.7×10−7), angiotensin I converting enzyme (ACE) (P=6.4×10−3), and solute carrier family 22 member 1 (SLC22A1) (P=7.0×10−5) over childhood development. In contrast, we observed a significant decrease in expression of two alternative CYP3A7 transcripts (P=1.5×10−5 and 3.0×10−5) over development. The analysis of genome-wide changes detected transcripts in the following genes with significant changes in mRNA expression (P<1×10−9 with false discovery rate<5×0−5): ADCY1, PTPRD, CNDP1, DCAF12L1 and HIP1. Gene set analysis determined ontogeny-related transcriptomic changes in the renin–angiotensin pathway (P<0.002), with lower expression of the pathway, in general, observed in liver samples from younger participants. Conclusion Considering that the renin–angiotensin pathway plays a central role in blood pressure and plasma sodium concentration, and our observation that ACE and PTPRD expression increased over the spectrum of childhood development, this finding could potentially impact the dosing of an entire class of drugs known as ACE-inhibitors in pediatric patients.
Characterization of Ebola Virus Entry by Using Pseudotyped Viruses: Identification of Receptor-Deficient Cell Lines

ABSTRACT Studies analyzing Ebola virus replication have been severely hampered by the extreme pathogenicity of this virus. To permit analysis of the host range and function of the Ebola virus glycoprotein (Ebo-GP), we have developed a system for pseudotyping these glycoproteins into murine leukemia virus (MLV). This pseudotyped virus, MLV(Ebola), can be readily concentrated to titers which exceed 5 × 106 infectious units/ml and is effectively neutralized by antibodies specific for Ebo-GP. Analysis of MLV(Ebola) infection revealed that the host range conferred by Ebo-GP is very broad, extending to cells of a variety of species. Notably, all lymphoid cell lines tested were completely resistant to infection; we speculate that this is due to the absence of a cellular receptor for Ebo-GP on B and T cells. The generation of high-titer MLV(Ebola) pseudotypes will be useful for the analysis of immune responses to Ebola virus infection, development of neutralizing antibodies, analysis of glycoprotein function, and isolation of the cellular receptor(s) for the Ebola virus.
Milk cytokines and subclinical breast inflammation in Tanzanian women: effects of dietary red palm oil or sunflower oil supplementation

Previously, we have found that subclinical breast inflammation, as indicated by raised breastmilk concentrations of sodium and the inflammatory cytokine, interleukin‐8 (IL‐8), was highly prevalent in Bangladesh and associated with poor infant growth. In order to investigate further the prevalence of subclinical breast inflammation and to assess the impact of dietary intervention, we studied rural Tanzanian women taking part in a study of dietary sunflower or red palm oil supplementation during late pregnancy and lactation. We measured breastmilk concentrations of IL‐8, the anti‐inflammatory cytokine, transforming growth factor‐β2 (TGF‐β) and the ratio of sodium to potassium. We also estimated systemic inflammation by plasma concentrations of the acute phase proteins, α1‐acid glycoprotein and C‐reactive protein. There were highly significant intercorrelations among milk Na/K ratio and concentrations of IL‐8 and TGF‐β, the last only after treatment with bile salts which also improved TGF‐β recovery in the enzyme‐linked immunosorbent assay (ELISA). Plasma acute phase protein concentrations tended to correlate with milk Na/K ratio and IL‐8, suggesting that subclinical breast inflammation was related to systemic inflammation. Dietary supplementation with vitamin E‐rich sunflower oil but not provitamin A‐containing red palm oil decreased milk Na/K, IL‐8 and TGF‐β at 3 months postpartum; however, the effect was significant only for Na/K ratio. The results suggest that milk Na/K ratio, IL‐8, and TGF‐β all measure the same phenomenon of subclinical breast inflammation but that Na/K ratio, having the lowest assay variability, is the most useful. Subclinical breast inflammation may result in part from systemic inflammation and may be improved by increased dietary intake of vitamin E‐rich sunflower oil.
A randomized comparison of doxorubicin alone versus doxorubicin plus cyclophosphamide in the management of advanced or recurrent endometrial carcinoma: A Gynecologic Oncology Group study.

PURPOSE From 1979 to 1984, 356 eligible patients with advanced or recurrent endometrial carcinoma no longer amenable to therapy with surgery, radiotherapy, or progestins were treated with doxorubicin alone or doxorubicin in combination with cyclophosphamide. PATIENTS AND METHODS Patients were randomized to receive doxorubicin 60 mg/m2 intravenously (i.v.) with or without cyclophosphamide 500 mg/m2 i.v. every 3 weeks for eight drug courses. All patients had received prior therapy with progestins with subsequent progression of disease. No patients had received prior therapy with cytotoxic drugs. Of 356 patients, 300 had measurable disease. RESULTS Among 132 patients treated with doxorubicin alone, there were seven complete responses (5%), 22 partial responses (17%), 73 with stable disease (55%), and 30 with increasing disease within 2 months of study entry (23%). For the 144 patients who received the combination, there were 18 complete responses (13%), 25 partial responses (17%), 75 with stable disease (52%), and 26 with increasing disease (18%). The median progression-free interval for those patients who received doxorubicin alone was 3.2 months, while it was 3.9 months for those who received the combination. The median survival duration for doxorubicin patients was 6.7 months, while it was 7.3 months for the combination patients. None of the unadjusted estimates of treatment differences are statistically significant. Prognostic features that had an impact on outcome included one factor associated with an increased likelihood of response (presence of measurable lung metastases) and four features associated with a poorer survival (poor performance status [PS] of 2 or 3, high pathologic grade, and presence of liver metastases or other intraabdominal disease). If these features are taken into account in multivariate analyses, there is no statistically significant evidence for differences in response rates (relative odds of response, 1.58; P = .06, one-tailed test), and survival duration is slightly longer in the combination regimen (17% reduction in death rate; P = .048). CONCLUSION The combination of doxorubicin plus cyclophosphamide thus appears to offer a small advantage over doxorubicin alone in the management of endometrial carcinoma at the expense of more frequent and severe myelosuppression and gastrointestinal toxicity.
Expectations for Future Relationship Satisfaction: Unique Sources and Critical Implications for Commitment

Contemporary perspectives on relationship commitment posit that intimates decide whether or not to maintain a relationship based on their commitment to that relationship, and that they base such commitment partially on their current satisfaction with that relationship. Nevertheless, given that ending a relationship requires knowing about both the current state of the relationship and the likely future state of the relationship, we propose that people base their commitment to a relationship more on their expected future satisfaction with the relationship than on their current satisfaction with that relationship. Six studies provided evidence for these ideas. Study 1 demonstrated that expected satisfaction is shaped by not only current satisfaction but also several unique indicators of the likelihood of future satisfaction, including anticipated life events, plans to improve the relationship, and individual differences. Then, using a combination of cross-sectional, experimental, and longitudinal methods, Studies 2 through 6 demonstrated that (a) expected satisfaction was a stronger predictor of relationship commitment, maintenance behaviors, and/or divorce than was current satisfaction and (b) expected satisfaction mediated the association between current satisfaction and these outcomes. These findings highlight not only the need to incorporate expected satisfaction into extent perspectives on commitment, but also the importance of expectations for decision-making processes more broadly.
NIMH Diagnostic Interview Schedule for Children Version IV (NIMH DISC-IV): description, differences from previous versions, and reliability of some common diagnoses.

OBJECTIVE To describe the National Institute of Mental Health Diagnostic Interview Schedule for Children Version IV (NIMH DISC-IV) and how it differs from earlier versions of the interview. The NIMH DISC-IV is a highly structured diagnostic interview, designed to assess more than 30 psychiatric disorders occurring in children and adolescents, and can be administered by "lay" interviewers after a minimal training period. The interview is available in both English and Spanish versions. METHOD An editorial board was established in 1992 to guide DISC development and ensure that a standard version of the instrument is maintained. Preliminary reliability and acceptability results of the NIMH DISC-IV in a clinical sample of 84 parents and 82 children (aged 9-17 years) drawn from outpatient child and adolescent psychiatric clinics at 3 sites are presented. Results of the previous version in a community sample are reviewed. RESULTS Despite its greater length and complexity, the NIMH DISC-IV compares favorably with earlier versions. Alternative versions of the interview are in development (the Present State DISC, the Teacher DISC, the Quick DISC, the Voice DISC). CONCLUSIONS The NIMH DISC is an acceptable, inexpensive, and convenient instrument for ascertaining a comprehensive range of child and adolescent diagnoses.
Notas corológicas sobre algas rojas Rhodomelaceae de las Islas Canarias

21 especies de Rhodomelaceae (Rhodophyta), mayoritariamente especies del genero Polysiphonia, son citadas por primera vez para alguna isla del archipielago canario. Se presentan datos sobre el habitat, la fenologia y la distribucion regional de las especies.
Stability of the different AlOOH phases under pressure

The pressure effects on three different AlOOH structures (α, γ, and δ phases) are systematically analyzed by density functional theory with different exchange and correlation energy functional approximations, namely two local, two generalized-gradient approximation (GGA), and two GGA for solids (GGAsol). Phase stability, compressibility and hydrogen bond evolution are studied in a range of pressures from 0 to 30 GPa. In general, the use of GGAsol functionals is mandatory in order to have the correct phase stability order, a good description of the hydrogen bonds, and a close agreement with the experimental lattice parameters at the various pressures. Pressure-induced hydrogen-bond symmetrization is found in γ and δ phases at high compression, while the hydrogen bonds in the α phase remain asymmetric. A detailed analysis of the uncertainties on the values of the bulk moduli and their pressure derivative at zero pressure deduced by fitting calculated or experimental (P,V) data is also presented.
Patient-reported outcome measurement in drug discovery: a tool to improve accuracy and completeness of efficacy and safety data

ABSTRACT Introduction: Patient-reported outcomes (PROs) reflect how patients feel and function as conveyed directly by patients themselves, for example symptoms and physical functioning. PRO measures can be included in any phase of product development as primary, secondary, or exploratory endpoints to understand the impact of treatment on the patient experience. Areas covered: In this review, the authors describe approaches commonly used to assess PROs in drug development programs, including how to select or develop outcomes and measures, implement these in trials, and analyze data. Barriers and facilitators for effectively including PROs in clinical trials are discussed, and strategies for making labeling claims based on PRO data are noted. Expert opinion: Early planning with PRO experts is recommended to assure a successful PRO strategy in a product development program. Outcomes that are meaningful to patients should be rationally identified early in a product development program based on qualitative work, literature search and/or assumed mechanism of action. Measures corresponding to those outcomes should be selected or developed, with demonstration of robust psychometric properties in a related patient population. Ideally, these measures will be tested prior to a pivotal trial to support the design and analysis in the pivotal trial. Selection of timing and mode of assessments should be specified a priori and justified. If a labeling claim is sought, a statistical plan should be pre-specified. Strategies to minimize and handle missing data in analyses should be planned up front.
Abrupt changes in fibrillatory wave characteristics at the termination of paroxysmal atrial fibrillation in humans.

AIMS We investigated the process of spontaneous termination of atrial fibrillation (AF) to determine its time course from the surface ECG. METHODS AND RESULTS We studied fibrillatory waves in Holter recordings of paroxysmal and sustained AF. Following QRS-T cancellation dominant frequencies (DFs) were computed and the relationship of DF to termination was scrutinized. For 57 episodes of paroxysmal AF (PAF) in 24 patients, DF ranged from 4.4 to 6.5 Hz (5.2 +/- 0.4 Hz) compared to 5.8 to 7.4 Hz (6.6 +/- 0.6 Hz) for sustained AF recordings. Comparison of the atrial frequency of the ultimate to the penultimate second demonstrated a drop in frequency in 51 of 57 episodes, P < 0.00001. No comparable change was seen at longer time periods. Moments of comparably low frequency without termination were only occasionally seen in patients with PAF but not in patients with sustained AF. CONCLUSION Low frequency fibrillation was found to be much more likely to terminate. Frequency changes preceding spontaneous termination were abrupt, in contrast to the gradual frequency drop reported with drug-induced termination. The analysis of fibrillatory wave characteristics and their change over time might be used to target specific moments for pacing therapy in patients with AF.
The immotile-cilia syndrome. A congenital ciliary abnormality as an etiologic factor in chronic airway infections and male sterility.

We investigated six men and a woman suspected of suffering from congenital immotility of cilia. All had chronic airway infections, and the men had immotile spermatozoa. The woman and three men had Kartagener's syndrome. The investigations included measurements of the mucociliary transport in the lower airways and ultrastructural studies of the sperm tails or respiratory cilia (or both). Mucociliary transport was significantly delayed. Sperm tails lacked dynein arms in five patients. Respiratory cilia from the women and two men lacked dynein arms and were irregularly oriented. The results support the hypothesis that a congenital defect in the cilia and sperm tails will cause chronic respiratory-tract infections and male sterility--the immotile-cilia syndrome. In about half these patients there will also be a situs inversus--i.e., Kartagener's syndrome.
Comparative Genomics of Sibling Fungal Pathogenic Taxa Identifies Adaptive Evolution without Divergence in Pathogenicity Genes or Genomic Structure

It has been estimated that the sister plant pathogenic fungal species Heterobasidion irregulare and Heterobasidion annosum may have been allopatrically isolated for 34–41 Myr. They are now sympatric due to the introduction of the first species from North America into Italy, where they freely hybridize. We used a comparative genomic approach to 1) confirm that the two species are distinct at the genomic level; 2) determine which gene groups have diverged the most and the least between species; 3) show that their overall genomic structures are similar, as predicted by the viability of hybrids, and identify genomic regions that instead are incongruent; and 4) test the previously formulated hypothesis that genes involved in pathogenicity may be less divergent between the two species than genes involved in saprobic decay and sporulation. Results based on the sequencing of three genomes per species identified a high level of interspecific similarity, but clearly confirmed the status of the two as distinct taxa. Genes involved in pathogenicity were more conserved between species than genes involved in saprobic growth and sporulation, corroborating at the genomic level that invasiveness may be determined by the two latter traits, as documented by field and inoculation studies. Additionally, the majority of genes under positive selection and the majority of genes bearing interspecific structural variations were involved either in transcriptional or in mitochondrial functions. This study provides genomic-level evidence that invasiveness of pathogenic microbes can be attained without the high levels of pathogenicity presumed to exist for pathogens challenging naïve hosts.
Cyclooxygenase‐2 up‐regulates CCR7 expression via AKT‐mediated phosphorylation and activation of Sp1 in breast cancer cells

Up‐regulation of cyclooxygenase‐2 (COX‐2) is frequently found in human cancers and is significantly associated with tumor metastasis. Our previous results demonstrate that COX‐2 and its metabolite prostaglandin E2 (PGE2) stimulate the expression of CCR7 chemokine receptor via EP2/EP4 receptors to promote lymphatic invasion in breast cancer cells. In this study, we address the underlying mechanism of COX‐2/PGE2‐induced CCR7 expression. We find that COX‐2/PGE2 increase CCR7 expression via the AKT signaling pathway in breast cancer cells. Promoter deletion and mutation assays identify the Sp1 site located at the −60/−57 region of CCR7 gene promoter is critical for stimulation. Chromatin immunoprecipitation (ChIP) assay confirms that in vivo binding of Sp1 to human CCR7 promoter is increased by COX‐2 and PGE2. Knockdown of Sp1 by shRNA reduces the induction of CCR7 by PGE2. We demonstrate for the first time that AKT may directly phosphorylate Sp1 at S42, T679, and S698. Phosphorylation‐mimic Sp1 protein harboring S42D, T679D, and S698D mutation strongly activates CCR7 expression. In contrast, change of these three residues to alanine completely blocks the induction of CCR7 by PGE2. Pathological investigation demonstrates that CCR7 expression is strongly associated with phospho‐AKT and Sp1 in 120 breast cancer tissues. Collectively, our results demonstrate that COX‐2 up‐regulates CCR7 expression via AKT‐mediated phosphorylation and activation of Sp1 and this pathway is highly activated in metastatic breast cancer. J. Cell. Physiol. 228: 341–348, 2013. © 2012 Wiley Periodicals, Inc.
Billing mechanism design in an autonomous demand side management in a smart distribution network

In an autonomous demand-side management (A-DSM), there is an interaction between the customers in addition to the conventional interaction among the utility and the customers. Most prior works on A-DSM have not impacted a distribution grid in calculating the customers' payment. In this paper, a distributed billing mechanism is suggested for A-DSM that takes into account not only the load profile and the load flexibility of each consumer, but also the effect of the consumptions' position in the grid, i.e., the impact of each customer's load on the power loss and the voltage profile deviation in the distribution network. The A-DSM program in this study includes both the load reduction and the load shifting approaches within a 24-hour scheduling time scope. The efficiency of the proposed mechanism is investigated on several distribution networks via simulation. The results show that while the proposed mechanism considers the power loss and the reactive power issues of distribution network, its efficiency is acceptable in the sense of total cost, Peak to Average Ratio and fairness.