Miracle-dz/UniFAR-FTUs huggingface dataset:
Astrocytes as eicosanoid‐producing cells

A variety of prostaglandins and leukotrienes, together with thromboxane and prostacyclin metabolites, can be detected in central nervous tissues and in cerebrospinal fluid. Defined cultures of astrocytes have revealed these cells to be a major source of eicosanoids. In common with other eicosanoid‐producing cells, agents such as calcium ionophores and phorbol esters are potent stimuli for promoting release. While in other tissues agonists for receptors linked to calcium mobilisation prompt eicosanoid release, this does not seem to be the case in astrocytes, though a range of such receptors are present. The notable exceptions to this observation are adenosine triphosphate and adenosine diphosphate, presumably acting through P2 purinergic receptors. Many cell types in the CNS are targets for eicosanoids, possessing receptors linked to adenylate cyclase or phospholipase C. An appreciation of the functional significance of activation of these receptors in just now begining. Eicosanoids have effects in the CNS that involve not only the vascular supply but also synaptic modulation and immune regulation.
Correlation Between EGFR Mutation Status and Computed Tomography Features in Patients With Advanced Pulmonary Adenocarcinoma

Purpose: To correlate computed tomography (CT) imaging features and epidermal growth factor receptor (EGFR) mutation status in patients with advanced lung adenocarcinoma. Materials and Methods: Patients with advanced pulmonary adenocarcinoma who were diagnosed between January 1, 2009 and December 31, 2011 and who had available chest CT and their tumors analyzed for EGFR mutations at a university hospital were enrolled in this retrospective study. Two radiologists independently evaluated the CT images and recorded the target lesion's size, shape, margin, density, and the presence or absence of an air bronchogram and calcification. Results: One hundred and forty-nine patients were enrolled into this study (66 men, 83 women), with a mean age of 63±11 years (range 32 to 89 y). Seventy-eight (52.3%) patients had EGFR mutations. The tumors in the patients harboring no EGFR mutations (EGFR wild type) were larger than in those whose tumors harbored EGFR mutations (P=0.01). An irregular shape was more common in the tumors with wild-type EGFR (P=0.01), and an oval shape was more common in tumors with EGFR mutations. Tumors with exon 21 mutations were larger than those with exon 19 deletions (P=0.02). Air bronchograms were more common in tumors with exon 19 deletions than in those with wild-type EGFR or exon 21 mutations (P=0.004 and 0.01, respectively). Calcification was more common in the tumors with wild-type EGFR than in those with EGFR mutations (P=0.03). Conclusions: Adenocarcinomas with wild-type EGFR were significantly associated with larger tumors and an irregular shape. In particular, calcification was more common in the tumors with wild-type EGFR than in those with EGFR mutations. In addition, air bronchograms were more common in the tumors with exon 19 deletions.
How Should Acquirers Select Advisors ? Persistence in Investment Bank Performance

We document significant persistence in the average announcement returns to acquisitions advised by an investment bank. This principally results from persistence in the component of returns related to deal characteristics. Completion probabilities and speed of completion are also associated with superior future shareholder returns. Clients should therefore base their advisor selection decisions on past performance measures. We find that in practice, these measures are overlooked and mandates are given instead on the basis of past market share, even though this variable is a significantly negative predictor of future performance. Such behavior is consistent with the widespread dissemination of market share league tables in the investment banking industry. The publication of league tables based on value creation may improve both clients’ selection decisions and advisors’ incentives to turn away bad deals. __________________ We thank Florian Ederer, Dirk Jenter, Adam Kolasinski, Stew Myers, Max Tse and seminar participants at MIT Sloan for valued input.
Sant'Egidio et les métamorphoses de la fabrique de la paix : une étude comparée Mozambique-Burundi

Mediateur providentiel au Mozambique, operateur de paix reconnu pour ses methodes et sa discretion au Burundi, la communaute catholique et romaine de Sant'Egidio est un acteur atypique et singulier de la resolution des conflits. "Naturelle", son expertise pacificatrice n'a jamais ete problematisee au regard des conflictualites dans lesquelles elle est intervenue. Notre etude, sur une base comparative, ambitionne de depasser les prenotions entourant la gestion des conflits armes en privilegiant une approche articulee en termes de sociologie politique de dispositifs internationaux de fabrique de la paix. Les deux premieres parties, historiquement situees, partagent la meme demarche : problematiser l'evidence et la necessite des pratiques mediatrices de Sant'Egidio au Mozambique et au Burundi. L'enjeu est de retrouver les connexions, les rencontres, les jeux de force et les strategies qui ont contribue a l'emergence de la paix egidienne. C ette derniere doit etre mise en relation avec les evolutions des pratiques internationales de pacification dont elle participe et qui conditionnent son efficience. Tel est l'objet de la troisieme partie. L'etude des mediations africaines de la Communaute s'ouvre alors a l'ensemble des strategies enchevetrees concourant a la production de la paix en Afrique. En conclusion, il s'agira d'evenementialiser la "diplomatie parallele" de Sant'Egidio, a travers une breve archeologie des categories de pensees qui fondent sa reconnaissance et sa legitimite en tant qu'operateur de paix. Que nous revele, in fine, l'action de Sant'Egidio quant aux modalites contemporaines du gouvernement des guerres des pauvres ?
Mechanisms of Bisphosphonate Effects on Osteoclasts, Tumor Cell Growth, and Metastasis

Bisphosphonates are potent inhibitors of osteoclast-mediated bone resorption that also exhibit antitumor activity. There is now extensive in vitro evidence that bisphosphonates inhibit proliferation and induce apoptosis of tumor cell lines. In addition, they appear to inhibit tumor cell adhesion and invasion of the extracellular matrix. These data are supported by a growing body of evidence from animal models demonstrating that bisphosphonates can reduce skeletal tumor burden. This may reflect direct antitumor effects or indirect effects via osteoclast inhibition and alteration of the bone microenvironment. Research has begun to shed light on the complex mechanisms by which bisphosphonates inhibit bone resorption and interfere with the formation and growth of bone lesions. Nitrogen-containing bisphosphonates inhibit protein prenylation and thereby short-circuit intracellular signaling via small guanine triphosphatases, such as Ras, which require membrane localization. As a result of these biochemical effects on the mevalonate pathway, bisphosphonates appear to modulate the expression of bcl-2 leading to caspase-dependent apoptosis, inhibit matrix metalloproteinases, downregulate &agr;v&bgr;3 and &agr;v&bgr;5 integrins, and increase expression of osteoprotegerin, thereby antagonizing osteoclastogenesis. Further preclinical studies are ongoing to fully elucidate these biochemical mechanisms, and well-designed clinical trials are necessary to investigate whether the antitumor potential of bisphosphonates can be realized in the clinical setting.
The NAM2 proteins from S. cerevisiae and S. douglasii are mitochondrial leucyl‐tRNA synthetases, and are involved in mRNA splicing.

We have cloned and sequenced the NAM2 gene of Saccharomyces douglasii, which is a homologue of the NAM2 gene of Saccharomyces cerevisiae. The wild‐type S.douglasii gene possesses the suppressor functions of the mutant S. cerevisiae NAM2‐1 allele, being able to cure a mitochondrial b14 maturase deficiency. By sequence comparisons and direct measurements we have demonstrated that the NAM2 genes encode mitochondrial leucyl tRNA synthetases (EC 6.1.1.4.). Using a derivative of the NAM2 gene, where the expression of the gene is under the control of the UAS GAL10, we have shown that the processing of the pre‐mRNA from the two mosaic genes oxi3 and cob‐box is impaired when transcription of the gene is repressed. These results lead us to conclude that the mitochondrial leucyl tRNA synthetase is involved in protein synthesis and mRNA splicing. Sequence comparisons show that the mitochondrial and Escherichia coli leucyl tRNA synthetases are highly homologous; however, significant features which may be important for the splicing functions of the mitochondrial enzymes are absent from the bacterial enzyme.
How self-determination theory can assist our understanding of the teaching and learning processes in medical education. AMEE Guide No. 59

Self-determination Theory (SDT), designed by Edward Deci and Richard Ryan, serves among the current major motivational theories in psychology. SDT research has been conducted in many areas, among which are education and health care, but its applications in medical education are rare. The potential of SDT to help understand processes in medical education justifies this Guide. SDT is explained in seven principles, one of which is the distinction of three innate psychological needs of human beings: for competence, for autonomy and for relatedness. Further, SDT elaborates how humans tend to internalise regulation of behaviour that initially has been external, in order to develop autonomous, self-determined behaviour. Implications of SDT for medical education are discussed with reference to preparation and selection, curriculum structure, classroom teaching, assessments and examinations, self-directed learning, clinical teaching, students as teachers and researchers, continuing professional development, faculty development and stress among trainees.
Attribute-Based Conditional Proxy Re-Encryption with Chosen-Ciphertext Security

Proxy re-encryption is a cryptographic primitive which enables a ciphertext encrypted under a delegator's public key to be translated into a ciphertext of a delegatee by a semi-trusted proxy. Conditional proxy re-encryption (CPRE) is a variant of proxy re-encryption which allows the delegator to control the delegation of decryption rights with certain conditional value. The existing CPRE schemes left an open problem about how to construct CCA-secure CPRE schemes supporting Boolean predicates over conditions. In this paper, we propose attribute-based CPRE (AB-CPRE) in which the delegator could implement attributed-based control on the delegation of decryption rights by setting conditions in the form of access structure and attribute set. AB-CPRE is suitable for applications where fine-grained control of the decryption delegation is necessary. We formalize definitions and security notions for AB-CPRE and prove that the proposed scheme is chosen-ciphertext secure under the 3-Quotient Decision Bilinear Diffie-Hellman (3-QDBDH) assumption.
DNA metabarcoding reveals that 200‐μm‐size‐fractionated filtering is unable to discriminate between planktonic microbial and large eukaryotes

Microeukaryotic plankton (0.2–200 μm) are critical components of aquatic ecosystems and key players in global ecological processes. High‐throughput sequencing is currently revolutionizing their study on an unprecedented scale. However, it is currently unclear whether we can accurately, effectively and quantitatively depict the microeukaryotic plankton communities using traditional size‐fractionated filtering combined with molecular methods. To address this, we analysed the eukaryotic plankton communities both with, and without, prefiltering with a 200 μm pore‐size sieve –by using SSU rDNA‐based high‐throughput sequencing on 16 samples with three replicates in each sample from two subtropical reservoirs sampled from January to October in 2013. We found that ~25% reads were classified as metazoan in both size groups. The species richness, alpha and beta diversity of plankton community and relative abundance of reads in 99.2% eukaryotic OTUs showed no significant changes after prefiltering with a 200 μm pore‐size sieve. We further found that both >0.2 μm and 0.2–200 μm eukaryotic plankton communities, especially the abundant plankton subcommunities, exhibited very similar, and synchronous, spatiotemporal patterns and processes associated with almost identical environmental drivers. The lack of an effect on community structure from prefiltering suggests that environmental DNA from larger metazoa is introduced into the smaller size class. Therefore, size‐fractionated filtering with 200 μm is insufficient to discriminate between the eukaryotic plankton size groups in metabarcoding approaches. Our results also highlight the importance of sequencing depth, and strict quality filtering of reads, when designing studies to characterize microeukaryotic plankton communities.
Cognitive functioning in schizophrenia: a consensus statement on its role in the definition and evaluation of effective treatments for the illness.

BACKGROUND Truly effective treatments for schizophrenia require much more than clinical efficacy. Symptom improvement is all that is required to demonstrate clinical efficacy. However, for a treatment to be effective in a wide-ranging manner, improvement in various life domains, such as social functioning, independent living, and employment, should also be found. Thus, a much wider range of improvements, not widely produced by previous treatments, is required to take treatment for schizophrenia to a new level of effectiveness. CONSENSUS PROCESS A teleconference consensus meeting was held with the bylined authors on December 10, 2002, to explore the factors that hinder the most effective treatments for schizophrenia. We argue that a possible unifying factor underlying these apparently disparate domains of effective treatment is cognitive functioning, which is impaired in people with schizophrenia. Treatment of cognitive dysfunction may have a central role in increasing the breadth of effective treatment for schizophrenia. CONCLUSIONS Novel antipsychotics and specific cognitive-enhancing medications have preliminarily been shown to have cognitive benefits that might lead to broader effectiveness of treatments, eventually reflected in improvements in the daily lives of patients. These treatments may have their greatest impact when combined with focused psychological interventions. While the research to date does not provide a large number of successes, this area will be one of considerable research interest for the next decade, with developments likely to be very important to clinicians treating patients with schizophrenia.
Timing of Surgery and the Role of Cytoreductive Chemotherapy in Patients with Advanced Ovarian Carcinoma

We retrospectively selected 27 consecutive patients with advanced ovarian carcinoma (15 stage III, 11 stage IV and 1 relapse) who had an unresectable intraabdominal tumor at presentation and prospectively evaluated the overall treatment outcome. Patients were initially treated with chemotherapy consisting of cisplatin-containing regimens in 20 cases, adriamycin and cyclophosphamide in 5, and melphalan in 2. Treatment was continued until maximal tumor response or progression. Following a median of 6 cycles of chemotherapy, all patients underwent debulking surgery. Six women were without evidence of disease and 13 had minimal residual disease after surgery, for an overall 70% rate of optimal debulking. Patients with evidence of disease at laparotomy were treated with 5 additional cycles of chemotherapy, and response was then assessed at laparotomy except for patients with progressive disease. Nine (33%) patients were pathologic complete responders at the end of the entire treatment program. Overall median survival time was 26 months, with a median relapse-free survival of 33 months. Tumor responses were not associated with any particular chemotherapy regimen. The results achieved in this series of patients together with the data from the literature suggests that use of a cytoreductive chemotherapy of short duration has the potential of increasing the rate of optimal debulking surgery. Furthermore, it may contribute to a better disease control in women with bulky ovarian carcinoma compared to the present strategy, which consists of surgery followed by chemotherapy.
Anemia Evaluation and Erythropoietin Dose Requirement Among Hemodialysis Patients: a Multicenter Study.

INTRODUCTION Both anemia and high doses of erythropoietin have been associated with increased mortality among dialysis patients. This study was conducted to evaluate the effective dose of erythropoiesis-stimulating agents. MATERIALS AND METHODS This multicenter nationwide cross-sectional study assessed adult patients on hemodialysis for at least 3 months from 80 hemodialysis centers in Iran. Demographic data, erythropoietin dose, and laboratory data were collected. RESULTS A total of 7009 prevalent hemodialysis patients were enrolled. Fifty-five percent of the patients had their hemoglobin levels within the target values. In those with a hemoglobin level of 8 g/dL to 10 g/dL, an erythropoietin dose of 10000 IU/wk to 12000 IU/wk led to a significant increase in hemoglobin level. A mean erythropoietin dose of 7700 IU/wk was effective in maintaining the target hemoglobin of 10 g/dL to 12 g/dL during a 3-month follow-up period. Improvement in hemoglobin level was associated with male sex, diabetes mellitus, and hemodialysis adequacy, and its deterioration with lower parathyroid hormone, calcium-phosphorus product, and creatinine levels; malnutrition; transfusion; and angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (R2 = 29.1%, P < .001). A dosage of 66.5 IU/kg/wk led to 1 g/dL increase in hemoglobin in anemic patients. CONCLUSIONS Data suggested that an estimated erythropoietin dose of 66.5 IU/kg/wk for each 1 g/dL hemoglobin level below the target could be used as a guide for prescription. A dosage of about 8000 IU/wk could help maintaining hemoglobin within the target. A longitudinal study is needed to estimate the required erythropoietin dose.
A prospective, open-label treatment trial to compare the effect of IFNβ-1a (Avonex®), IFNβ-1b (Betaseron®), and glatiramer acetate (Copaxone®) on the relapse rate in relapsing-remitting multiple sclerosis: results after 18 months of therapy

We previously reported results of a 12 month prospective, non-randomized, open-label treatment trial of immunomodulatory therapy in patients with relapsing-remitting multiple sclerosis (RRMS). We now report the results after 18 months of follow-up. Our primary objective was to compare the effect of INFβ-1a (Avonex®), IFNβ-1b (Betaseron®), and Glatiramer Acetate (GA, Copaxone®) to no treatment on the relapse rate in patients with RRMS. One hundred and fifty-six consecutive patients with clinically definite RRMS with a Kurtzke scale (EDSS) score of 4 or less were followed for 18 months. Prior 2-year relapse history and available chart information was carefully reviewed at the time of enrollment. Thirty-three of 156 elected no treatment at enrollment; 40 elected IFNβ-1a, 41 IFNβ-1b, and 42 chose GA. There were no statistically significant differences among the four groups at enrollment. After 18 months of treatment, 122 patients remained in their original treatment group. Compared to the untreated group (1.02), mean annualized number of relapses was significantly reduced only in the GA (0.49, P40.0001) and IFNβ-1b groups (0.55, P=0.001) in contrast to the IFNβ-1a treated patients (0.81, P=0.106) who did not show a significant reduction. Despite limitations of the study design, the results provide helpful clinical information regarding the relative efficacy of each therapy in mildly affected treatment naïve RRMS patients.
Childhood predictors of drunkenness in late adolescence among males: a 10-year population-based follow-up study.

AIMS To study childhood precursors of drunkenness frequency among 18-year-old boys in a representative, nation-wide 10-year follow-up study. DESIGN In 1989, a general population sample of 2,946 8-year-old boys was collected. Three different informant sources were used: parents, teachers and the boys themselves. The follow-up was 10 years later in 1999, when the boys were called up for their obligatory military service at age 18. Information about drunkenness frequency was obtained from 78.3% (n=2306) of the original sample. SETTING Finland, nation-wide; in 1989 at schools, in 1999 at the obligatory military call-up. PARTICIPANTS General population sample of Finnish boys born in 1981. MEASUREMENTS At age 8, the Rutter A2 scale, Rutter B2 scale and Child Depression Inventory (CDI) were used. At age 18, self-reported drunkenness frequency during the previous 6 months was determined. FINDINGS Of the subjects, 15.0% reported never being drunk from alcohol, 74.6% reported being occasionally drunk and 10.4% reported being drunk at least once a week during the previous 6 months. After adjusting for other variables, teacher's estimate of the child's problem behaviour at age 8 predicted frequent drunkenness in late adolescence. Hyperactive problems predicted both occasional and frequent drunkenness. Conduct problems at age 8 predicted only frequent drunkenness. High teacher-reported scores of emotional problems predicted lower occurrence of drunkenness-orientated alcohol use. CONCLUSIONS The educational system has a potential role in detecting boys at risk of later risk-taking behaviours, such as frequent drunkenness. Early interventions in children with conduct problems and hyperactivity are called for.
Generation of mariner-based transposon insertion mutant library of Bacillus sphaericus 2297 and investigation of genes involved in sporulation and mosquito-larvicidal crystal protein synthesis.

Bacillus sphaericus has been used with great success in mosquito control programs worldwide. Under conditions of nutrient limitation, it undergoes sporulation via a series of well defined morphological stages. However, only a small number of genes involved in sporulation have been identified. To identify genes associated with sporulation, and to understand the relationship between sporulation and crystal protein synthesis, a random mariner-based transposon insertion mutant library of B. sphaericus strain 2297 was constructed and seven sporulation-defective mutants were selected. Sequencing of the DNA flanking of the transposon insertion identified several genes involved in sporulation. The morphologies of mutants were determined by electron microscopy and synthesis of crystal proteins was analyzed by SDS-PAGE and Western blot. Four mutants blocked at early stages of sporulation failed to produce crystal proteins and had lower larvicidal activity. However, the other three mutants were blocked at later stages and were able to form crystal proteins, and the larvicidal activity was similar to wild type. These results indicated that crystal protein synthesis in B. sphaericus is dependent on sporulation initiation.