Miracle-dz/UniFAR-FTUs huggingface dataset:
The oncological outcomes and risk stratification in docetaxel chemotherapy for castration-resistant prostate cancer.

OBJECTIVE To clarify the risk factors and develop a refined risk-stratification model to help in the appropriate selection of docetaxel chemotherapy in patients with castration-resistant prostate cancer. METHODS This study included 97 Japanese patients with castration-resistant prostate cancer who were treated with 70-75 mg/m(2) docetaxel and 10 mg prednisone every 3 or 4 weeks from 2008 to 2013. The oncological outcomes and prognostic significance of clinicopathological factors were analyzed, and significant prognostic factors were used to develop a risk-stratification model. RESULTS Prostate-specific antigen decline was observed in 75 patients (77.3%), including 43 (44.3%) who achieved a prostate-specific antigen decline of ≥ 50%. The median progression-free survival and overall survival were 5.1 and 20.8 months, respectively. Univariate analysis identified performance status, alkaline phosphatase value, visceral metastasis, duration from diagnosis, duration from initiation of hormone treatment and prior treatment with estramustine as significant predictors of overall survival. Among these, alkaline phosphatase value, visceral metastasis and duration from initiation of hormone treatment were independent prognostic factors in multivariate analysis. Furthermore, risk classification according to the number of independent risk factors present effectively stratified survival among docetaxel-treated castration-resistant prostate cancer patients. CONCLUSIONS Oncologic outcomes in Japanese patients with castration-resistant prostate cancer receiving docetaxel chemotherapy were comparable to or slightly better than those in Western populations, and the risk-stratification model developed in this study may help to predict prognosis and contribute to the selection of suitable therapy after castration resistance.
Generalised anxiety disorder in children and adolescents.

INTRODUCTION Generalised anxiety disorder (GAD) in a child or adolescent is excessive worry and tension about everyday events that the child or adolescent cannot control and that is expressed on most days for at least 6 months, to the extent that there is distress or difficulty in performing day-to-day tasks. METHODS AND OUTCOMES We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of pharmacological treatments for generalised anxiety disorder in children and adolescents? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). RESULTS At this update, searching of electronic databases retrieved 949 studies. After deduplication and removal of conference abstracts, 417 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 310 studies and the further review of 107 full publications. Of the 107 full articles evaluated, one systematic review was added at this update. We performed a GRADE evaluation for six PICO combinations. CONCLUSIONS In this systematic overview, we categorised the efficacy for six interventions based on information about the effectiveness and safety of antidepressants, antipsychotics, benzodiazepines, buspirone, hydroxyzine, and pregabalin.
Quantitative analysis of both protein expression and serine / threonine post‐translational modifications through stable isotope labeling with dithiothreitol

While phosphorylation and O‐GlcNAc (cytoplasmic and nuclear glycosylation) are linked to normal and pathological changes in cell states, these post‐translational modifications have been difficult to analyze in proteomic studies. We describe advances in β‐elimination / Michael addition‐based approaches which allow for mass spectrometry‐based identification and comparative quantification of O‐phosphate or O‐GlcNAc‐modified peptides, as well as cysteine‐containing peptides for expression analysis. The method (BEMAD) involves differential isotopic labeling through Michael addition with normal dithiothreitol (DTT) (d0) or deuterated DTT (d6), and enrichment of these peptides by thiol chromatography. BEMAD was comparable to isotope‐coded affinity tags (ICAT; a commercially available differential isotopic quantification technique) in protein expression analysis, but also provided the identity and relative amounts of both O‐phosphorylation and O‐GlcNAc modification sites. Specificity of O‐phosphate vs. O‐GlcNAc mapping is achieved through coupling enzymatic dephosphorylation or O‐GlcNAc hydrolysis with differential isotopic labeling. Blocking of cysteine labeling by prior oxidation of a cytosolic lysate from mouse brain allowed specific targeting of serine / threonine post‐translational modifications as demonstrated through identification of 21 phosphorylation sites (5 previously reported) in a single mass spectrometry analysis. These results demonstate BEMAD is suitable for large‐scale quantitative analysis of both protein expression and serine / threonine post‐translational modifications.
Role of the bed nucleus of the stria terminalis in aversive learning and memory

Surviving threats in the environment requires brain circuits for detecting (or anticipating) danger and for coordinating appropriate defensive responses (e.g., increased cardiac output, stress hormone release, and freezing behavior). The bed nucleus of the stria terminalis (BNST) is a critical interface between the “affective forebrain”—including the amygdala, ventral hippocampus, and medial prefrontal cortex—and the hypothalamic and brainstem areas that have been implicated in neuroendocrine, autonomic, and behavioral responses to actual or anticipated threats. However, the precise contribution of the BNST to defensive behavior is unclear, both in terms of the antecedent stimuli that mobilize BNST activity and the consequent defensive reactions. For example, it is well known that the BNST is essential for contextual fear conditioning, but dispensable for fear conditioning to discrete conditioned stimuli (CSs), at least as indexed by freezing behavior. However, recent evidence suggests that there are circumstances in which contextual freezing may persist independent of the BNST. Furthermore, the BNST is involved in the reinstatement (or relapse) of conditioned freezing to extinguished discrete CSs. As such, there are critical gaps in understanding how the BNST contributes to fundamental processes involved in Pavlovian fear conditioning. Here, we attempt to provide an integrative account of BNST function in fear conditioning. We discuss distinctions between unconditioned stress and conditioned fear and the role of BNST circuits in organizing behaviors associated with these states. We propose that the BNST mediates conditioned defensive responses—not based on the modality or duration of the antecedent threat or the duration of the behavioral response to the threat—but rather as consequence the ability of an antecedent stimulus to predict when an aversive outcome will occur (i.e., its temporal predictability). We argue that the BNST is not uniquely mobilized by sustained threats or uniquely involved in organizing sustained fear responses. In contrast, we argue that the BNST is involved in organizing fear responses to stimuli that poorly predict when danger will occur, no matter the duration, modality, or complexity of those stimuli. The concepts discussed in this review are critical to understanding the contribution of the human BNST to fear and anxiety disorders.
A Study of Expansion Tube Gas Flow Conditions for Scramjet Combustor Model Testing

ow process inside an expansion tube facility. The work is a combined numerical/experimental eort. Axisymmetric, viscous, unsteady RANS simulations of the operation of an expansion tube have been performed. Additionally, measurements of observable quantities have been carried out to validate the simulations and to gain detailed physical insight into the operation of the facility. Here, a comparison of transient wall static pressure, shock Mach numbers and stagnation point pressures at the tube outlet have been selected for comparison. The transient test gas ow is then analyzed on grounds of the results of the numerical simulation.
Kinetics of stimulus-coupled secretion in dialyzed bovine chromaffin cells in response to trains of depolarizing pulses

Stimulus-secretion coupling in bovine chromaffin cells was investigated with whole-cell patch-clamp recordings and capacitance detection techniques to monitor exocytosis in response to trains of depolarizing pulses. Two kinetically discrete modes of exocytotic responses were observed. In one mode, the first depolarization of a train elicited a large increase in membrane capacitance (Cm; mean approximately 70 fF). This secretory mode was characterized by small Ca2+ requirements, relative insensitivity to the pipette Ca2+ chelator concentration, and rapid depletion of the secretory response. This mode of stimulus-secretion coupling was labile and was seen only in response to the first and, occasionally, the second stimulus train of whole-cell recordings. The second type of exocytotic response persisted for the remainder of the whole-cell recordings and consisted of two distinct phases. During the earliest pulses of a stimulus train, Ca2+ entry did not evoke Cm increases. Instead, Cm responses were elicited by later pulses, despite diminished Ca2+ entry per pulse caused by Ca2+ channel inactivation. The secretory phase was initiated after a specific "threshold" amount of Ca2+ had entered the cell, which was determined by the concentration, but not the binding kinetics, of the Ca2+ chelator in the pipette. In both the early and the secretory phases, the response of the cell was proportional to cumulative Ca2+ entry, regardless of current amplitude, pulse duration, or number of pulses. Threshold-type secretory kinetics has been described previously in peptide-secreting neurohypophysial (NHP) nerve terminals (Seward et al., 1995). Secretory kinetics with minimal Ca2+ requirements has not been observed in that preparation. Chromaffin cells appear to possess a broader repertoire of stimulus-secretion coupling modes than NHP terminals.
Inhibition of IL-2-dependent proliferation by a prostaglandin-dependent suppressor factor.

In the picryl chloride contact sensitivity system in mice, i.v. injections of trinitrobenzene sulfonic acid (TNBSA) prevents elicitation of delayed-type hypersensitivity reactions. This suppression is due in part to a non-specific, PG-dependent factor (TNBSA-F) that is induced by i.v. injection of TNBSA and is produced by pooled spleen and lymph node cells in vitro. Inasmuch as a role for lymphokines such as IL-2 has been postulated in delayed-type hypersensitivity, we determined the in vitro effects of TNBSA-F on the responsiveness of HT-2 target cells to IL-2. TNBSA-F induced a dose-dependent unresponsiveness of HT-2 cells to IL-2. The inhibitory activity was not present in supernatants from lymphoid cells of sham-treated mice. In the presence of indomethacin, spleen, and lymph node cells from TNBSA-immunized mice produced a factor whose activity was much reduced compared to TNBSA-F. This suggested that PG were required for TNBSA-F activity. However, PG alone did not induce the unresponsiveness because TNBSA-F but not sham-treated mice had inhibitory activity despite containing similar levels of PGE2. Rather, the combination of i.v. TNBSA injections and PG synthesis during production of TNBSA-F were required to produce a suppressive TNBSA-F. The inhibitory effect of TNBSA-F was not due to the presence of transforming growth factor-beta, soluble immune-response suppressor, INF-gamma, or JE in the factor preparation. Partial characterization showed a single peak of in vitro TNBSA-F activity (molecular mass approximately 35-55 kDa) by Sephadex G-200 gel filtration chromatography and by HPLC. In addition, TNBSA-F retained its activity after multiple cycles of freeze-thaw and heating for 1 h at 56 degrees C. The inhibitory effects of TNBSA-F on IL-2-induced proliferation suggest that suppression of delayed type hypersensitivity after i.v. administration of TNBSA may, in part, be due to a PG-dependent suppressor factor that inhibits the responsiveness of target cells to IL-2.
A Convex Model of Equilibrium Growth

Our aim in this paper is to exposit a convex model of equilibrium growth. The model is strictly in the Solow tradition. The model has two features which distinguish it from most other work on the subject. These are, first, that the model is convex on the technological side and, eecond, that fixed fatten are explicitly included. The difference between our model and the standard single sector growth model lies in the fact that the marginal product of capital does not converge to zero as the level of inputs go to infinity. Existence and characterization results are provided along with some preliminary analyses of taxation and international trade policies. It is shown that the long-run growth rate in per capita consumption depends, in the natural way, on the parameters describing tastes and technology. Finally, it is shown that some policies have growth effects while others affect only levels. It is demonstrated that in a free trade equilibrium with taxation national growth rates of consumption and output need not converge.
Managing by E-Mail: What E-mail Can Do for Engineering Project Management

E-mails are, rightly or wrongly, a staple of the information and communication technology for managing work and collaborative activities. This paper examines the value of the content of e-mail at a project level rather than at the often-studied level of the individual user. The dataset consists of e-mails authored by an engineering team associated with a large, complex, long term, systems integration project, typical of the aerospace, marine, and defense sectors. The research applied a qualitative content analysis methodology to classify the content (what the e-mail contains) and purpose (why the e-mail was sent) of the e-mail in the dataset. The results of the content analysis were compared and contrasted with secondary evidence from interviews and project documentation to enable a time-phased analysis. The findings show that classifying e-mail content by the categories of management, information, and problem-solving transactions revealed signatures that align with project phases and, more importantly, problems encountered. Finally, we found that the purpose of e-mail is not necessarily consistent with the designated job role or responsibility of the sender or recipient. This paper contributes to empirical data on the relation between communication and project performance and the changing nature of e-mail communication throughout the lifecycle of a project. The findings point to a new way to leverage e-mail content to “manage by e-mail”.
Debating humanitarian military interventions in the European public sphere

What kind of democracy might fit the developing Common Security and Defence Policy (CSDP) given the political developments and the evolution of public debate on security and defence issues over the last twenty years? Different model-designs for a more democratic European Union (EU) in general and a democratized Common Security and Defence Policy (CSDP) in particular have been proposed. This paper contributes to answering this question by investigating whether and in which ways Europeans were included in a transnational European debate on humanitarian military interventions after the Cold War (1990-2005/2006). The paper analyses a full sample of 108,677 newspaper articles published in the leading conservative and liberal newspapers of six EU member states, and the US as a comparative case. It demonstrates that the ‘national’ arenas of political communication are thematically intertwined and allow ordinary citizens to make up their minds about common European issues in this highly controversial and normatively particularly sensitive realm. Transnational political communication is currently not satisfyingly fed into representative democratic institutions. However, ‘hermetic communicative borders’ between national publics are non-existent and are a poor excuse for a lack of political will to democratise the EU – one way or the other.
Intratumoral CD3 and CD8 T-cell Densities Associated with Relapse-Free Survival in HCC

Tumor immune infiltration is a prognostic marker for relapse in patients with colorectal cancer. The Immunoscore methodology was extended to patients with hepatocellular carcinoma. The Immunoscore could predict the risk of postsurgical relapse and duration of relapse-free survival. Immune cells that infiltrate a tumor may be a prognostic factor for patients who have had surgically resected hepatocellular carcinoma (HCC). The density of intratumoral total (CD3+) and cytotoxic (CD8+) T lymphocytes was measured in the tumor interior and in the invasive margin of 65 stage I to IV HCC tissue specimens from a single cohort. Immune cell density in the interior and margin was converted to a binary score (0, low; 1, high), which was correlated with tumor recurrence and relapse-free survival (RFS). In addition, the expression of programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) was correlated with the density of CD3+ and CD8+ cells and clinical outcome. High densities of both CD3+ and CD8+ T cells in both the interior and margin, along with corresponding Immunoscores, were significantly associated with a low rate of recurrence (P = 0.007) and a prolonged RFS (P = 0.002). In multivariate logistic regression models adjusted for vascular invasion and cellular differentiation, both CD3+ and CD8+ cell densities predicted recurrence, with odds ratios of 5.8 [95% confidence interval (CI), 1.6–21.8] for CD3+ and 3.9 (95% CI, 1.1–14.1) for CD8+. Positive PD-L1 staining was correlated with high CD3 and CD8 density (P = 0.024 and 0.005, respectively) and predicted a lower rate of recurrence (P = 0.034), as well as prolonged RFS (P = 0.029). Immunoscore and PD-L1 expression, therefore, are useful prognostic markers in patients with HCC who have undergone primary tumor resection. Cancer Immunol Res; 4(5); 419–30. ©2016 AACR.
RNA-seq of Rice Yellow Stem Borer Scirpophaga incertulas Reveals Molecular Insights During Four Larval Developmental Stages

The yellow stem borer (YSB), Scirpophaga incertulas, is a prominent pest in rice cultivation causing serious yield losses. The larval stage is an important stage in YSB, responsible for maximum infestation. However, limited knowledge exists on the biology and mechanisms underlying the growth and differentiation of YSB. To understand and identify the genes involved in YSB development and infestation, so as to design pest control strategies, we performed de novo transcriptome analysis at the first, third, fifth, and seventh larval developmental stages employing Illumina Hi-seq. High-quality reads (HQR) of ∼229 Mb were assembled into 24,775 transcripts with an average size of 1485 bp. Genes associated with various metabolic processes, i.e., detoxification mechanism [CYP450, GSTs, and carboxylesterases (CarEs)], RNA interference (RNAi) machinery (Dcr-1, Dcr-2, Ago-1, Ago-2, Sid-1, Sid-2, Sid-3, and Sid-1-related gene), chemoreception (CSPs, GRs, OBPs, and ORs), and regulators [transcription factors (TFs) and hormones] were differentially regulated during the developmental stages. Identification of stage-specific transcripts made it possible to determine the essential processes of larval development. Comparative transcriptome analysis revealed that YSB has not evolved much with respect to the detoxification mechanism, but showed the presence of distinct RNAi machinery. The presence of strong specific visual recognition coupled with chemosensory mechanisms supports the monophagous nature of YSB. Designed expressed sequenced tags-simple-sequence repeats (EST-SSRs) will facilitate accurate estimation of the genetic diversity of YSB. This is the first report on characterization of the YSB transcriptome and the identification of genes involved in key processes, which will help researchers and industry to devise novel pest control strategies. This study also opens up a new avenue to develop next-generation resistant rice using RNAi or genome editing approaches.
Board Size, Firm Risk, and Equity Discount

type="main" xml:lang="en"> Prior literature documents that larger boards pursue conservative investment policies and that their decision outcomes are moderate, which promote an environment of risk aversion. I argue that this risk aversion hurts equity holders when firms hold a larger amount of long-term debt. Addressing potential endogeneity problems associated with board size, I find an equity discount associated with larger boards in firms that have greater amounts of long-term debt. On the other hand, larger boards are associated with an equity premium when firms have a greater short-term debt-to-assets ratio. The equity discount associated with larger boards disappears in firms with no long-term debt. Further analysis also indicates that firms with larger boards enjoy a better credit rating and a lower realized cost of debt. Overall, analysis in this study suggests that the association between board size and equity value is a function of a firm's debt structure.
Motivations behind Preferences for Local or Organic Food

ABSTRACT This article aims at understanding the food choice motives underlying consumer preferences for organic versus local food. A sample of 720 German consumers is employed to investigate self-stated preference for organic or local food and the underlying food choice motives of health, natural content, price, animal welfare, and sensory appeal. Consumers preferring organic over local food put comparatively higher value on the motives of natural content and animal welfare and less on sensory appeal and price. For both groups, however, natural content and animal welfare are the most important motives, followed by sensory appeal, and lastly health and price.
Dynamic Capabilities in Public Organizations

Abstract This article provides a review and synthesis of the extant literature on dynamic capabilities in public organizations. Although this theoretical perspective holds potential to enhance our limited understanding of how public organizations change in response to their increasingly turbulent and complex environments, it has received little attention in the public management field. Against this backdrop, this article seeks to contribute to future research on public sector change by advancing an analytical model that captures the antecedents, microfoundations and effects of dynamic capabilities in public organizations.