Miracle-dz/UniFAR-FTUs huggingface dataset:
Ageing and the Moses Illusion: Older adults fall for Moses but if asked directly, stick with Noah

Many people respond “two” to the question “How many animals of each kind did Moses take on the ark? ”, even though they know the reference should be to Noah. The Moses Illusion demonstrates a failure to apply stored knowledge (Erickson & Mattson, 1981). Of interest was whether older adults' robust knowledge bases would protect them from vulnerability to this illusion. Of secondary interest were any age differences in the memorial consequences of the illusion, and whether older adults' prior knowledge would protect them from later reproducing information from distorted questions (e.g., later saying that Moses took two animals of each kind on the ark). Surprisingly, older adults fell for the Moses Illusion more often than did younger adults. However, falling for the illusion did not affect older adults' later memory; they were less suggestible than young adults. Most importantly, older adults were more likely to recover from exposure to distorted questions and respond correctly. Explanations of these findings, drawing on theories of cognitive ageing, are discussed.
Development of the external genitalia in bovine fetuses.

The external genitalia in bovine fetuses were studied macroscopically, with special reference to the formation of the labia and the sexual differentiation. The age of fetuses was expressed in crown-rump length (CRL). The female urogenital fold budding on either side of the genital tubercle gradually approached the tip of the genital tubercle by the 33-cm stage and then began to enclose it with the companion fold on the other side, thus forming the labium pudendi which is equivalent to the labium minus pudendi of the human. The genital swellings, which are known to become the labia majora in the human, did not take part in the formation of the labia. They completely disappeared at the sites cranial to the genital tubercle by the l0-cm stage. The sex difference in differentiation of the external genitalia was first observed at the 2.7-cm stage, at which time in the male, the urogenital orifice and the anogenital raphe appeared at the sites caudal to the genital tubercle; in the female at the 2.9-cm stage, both structures were still not observable. The anogenital distance became clearly longer in male than in female, after 3.6-3.9-cm stages.
Application of confocal microscopy for surface and volume imaging of solid state nuclear track detectors

Inhalation of radon gas is considered a risk factor in the development of lung cancer. Solid state nuclear track detectors (SSNTDs) are often used for monitoring radon levels. We have previously shown that 3D imaging can help distinguish real tracks from artefact. In this study, we investigated particle tracks in nine SSNTDs using surface and volume visualisation from confocal microscope imaging. An Olympus LEXT OLS 4000 confocal microscope equipped with the Olympus LEXT Remote Development Kit was used to acquire z‐stack images and surface data from the SSNTDs. Surface and volume visualisation analysis methods were developed and applied to examine the data. The mean (standard deviation) depth of 45 tracks from the nine detectors was 9.5 (4.6) μm. The mean difference in track depth using the two analysis techniques was 0.08 μm, thus showing good agreement. Furthermore, volume visualisation should enable assessment of the structure of tracks deep in the detector.
Uracil–DNA Glycosylase Expression Determines Human Lung Cancer Cell Sensitivity to Pemetrexed

Uracil misincorporation into DNA is a consequence of pemetrexed inhibition of thymidylate synthase. The base excision repair (BER) enzyme uracil–DNA glycosylase (UNG) is the major glycosylase responsible for removal of misincorporated uracil. We previously illustrated hypersensitivity to pemetrexed in UNG−/− human colon cancer cells. Here, we examined the relationship between UNG expression and pemetrexed sensitivity in human lung cancer. We observed a spectrum of UNG expression in human lung cancer cells. Higher levels of UNG are associated with pemetrexed resistance and are present in cell lines derived from pemetrexed-resistant histologic subtypes (small cell and squamous cell carcinoma). Acute pemetrexed exposure induces UNG protein and mRNA, consistent with upregulation of uracil–DNA repair machinery. Chronic exposure of H1299 adenocarcinoma cells to increasing pemetrexed concentrations established drug-resistant sublines. Significant induction of UNG protein confirmed upregulation of BER as a feature of acquired pemetrexed resistance. Cotreatment with the BER inhibitor methoxyamine overrides pemetrexed resistance in chronically exposed cells, underscoring the use of BER-directed therapeutics to offset acquired drug resistance. Expression of UNG-directed siRNA and shRNA enhanced sensitivity in A549 and H1975 cells, and in drug-resistant sublines, confirming that UNG upregulation is protective. In human lung cancer, UNG deficiency is associated with pemetrexed-induced retention of uracil in DNA that destabilizes DNA replication forks resulting in DNA double-strand breaks and cell death. Thus, in experimental models, UNG is a critical mediator of pemetrexed sensitivity that warrants evaluation to determine clinical value. Mol Cancer Ther; 12(10); 2248–60. ©2013 AACR.
Do the 'Haves' Come Out Ahead in Shanghai Courts?

Drawing on 2,724 documents of adjudication decisions from Shanghai courts, this article tests the Galanter thesis that the stronger party tends to prevail over the weaker party in litigation. We find that the stronger parties not only win more often, but also do so by a large margin. Overall, institutional litigants fare better than individual litigants. When the litigants are classified by their organizational and social status, government agencies or governmentrelated companies are the biggest winners, enjoying an enormous advantage, and farmers are the most disadvantaged underdogs, with other individuals and companies in between. When controlling for legal representation, these winning gaps remain significant and sizable. The edge of the stronger parties recurs across categories of cases in different issue areas of the law. Echoing previous comparative studies, we cast doubt on the party capability theory. We speculate that the causes of judicial inequality in China lie not only in resource gaps but also in the roots of the law and the nature of the court.
The Subtype-Specific Effects of Droperidol on Action Potential Duration in Cellular and Computational Models of Long QT Syndrome

BACKGROUND: Droperidol is a highly potent butyrophenone used for the therapy of postoperative nausea and vomiting. Its cardiac safety in cardiovascular-healthy patients and those with long QT (LQT) syndrome is a matter of debate. In this study, we investigated whether droperidol has subtype-specific effects in cellular and computational models of LQT syndrome. METHODS: Left ventricular cardiac myocytes were isolated from adult guinea pig hearts. LQT1-like behavior was pharmacologically induced by chromanol 293B (10 &mgr;mol/L) and LQT2-like states by E4031 (10 &mgr;mol/L). Computational analysis was performed using the Luo-Rudy dynamic model. Data are given as mean ± SEM. RESULTS: In control myocytes, droperidol lengthened action potentials in a concentration-dependent manner with a maximal prolongation of 37%± 13% (n = 4) at a concentration of 0.6 &mgr;mol/L. In LQT1-like myocytes, droperidol (0.6 &mgr;mol/L) further prolonged action potentials by 31% ± 6% (n = 6) but shortened action potentials of LQT2-like myocytes by 11% ± 2% (n = 8). Computational modeling supported the concept that droperidol, in addition to the rapid component of the delayed K+ current, blocks depolarizing targets, such as the L-type Ca2+ current, the Na+-Ca2+ exchanger, and the Na+-K+ adenosine triphosphatase. CONCLUSIONS: Droperidol has more detrimental effects on cardiac repolarization of LQT1-like than of LQT2-like myocytes suggesting subtype-specific cardiotoxic effects in patients with LQT syndrome. The subtype specificity of droperidol seems to be caused by a complex interaction of droperidol with several different molecular targets. This interaction deserves further investigation to establish the feasibility of a subtype-directed approach in the perioperative management of patients with LQT syndrome.
Thirty years of viable but nonculturable state research: Unsolved molecular mechanisms

Abstract Viable but nonculturable (VBNC) cells were recognized 30 years ago; and despite decades of research on the topic, most results are disperse and apparently incongruous. Since its description, a huge controversy arose regarding the ecological significance of this state: is it a degradation process without real significance for bacterial life cycles or is it an adaptive strategy of bacteria to cope with stressful conditions? In order to solve the molecular mechanisms of VBNC state induction and resuscitation, researchers in the field must be aware and overcome common issues delaying research progress. In this review, we discuss the intrinsic characteristic features of VBNC cells, the first clues on what is behind the VBNC state’s induction, the models proposed for their resuscitation and the current methods to prove not only that cells are in VBNC state but also that they are able to resuscitate.
Extension of yeast artificial chromosomes by cosmid multimers.

Rapid advances in genome mapping have been made possible by the cloning of large genomic regions in yeast artificial chromosomes (YACs) (1). Expression studies of complex gene families may thus become feasible using YACs introduced into mammalian cells and transgenic animals (2). Unfortunately many YAC clones fail to span the entire region of interest and the addition of further genes or control sequences is often desirable. The ease with which YACs can be manipulated by homologydirected integration of transfected DNA (3) offers a variety of specific changes to be introduced. Although methods describing meiotic and mitotic crossing of YACs with overlapping regions allow enhancement of clone size, they are relatively time consuming and require a number of specialised procedures and equipment (4, 5). Here we describe a rapid technique for the targeted extension of YAC clones using human DNA contained on cosmids. The method takes advantage of the integration mechanism of exogenous DNA into yeast, which allows the targeting of the cosmid DNA to be mediated by homologous sequences; (i) within the insert, such as a cosmid clone which overlaps the DNA cloned in the YAC, and (ii) within the vector sequence present on the YAC arms and the cosmid vector itself. We show here the extension of a 300 kb YAC up to 800 kb by adding excess DNA of a 50 kb cosmid clone. The YAC clone used for the extension contains part of the human x light chain locus (6) but lacks a number of variable region genes. The human cosmid clone, cos 106 (7), contains five x light chain variable region genes which upon rearrangement and expression together with the genes on the YAC would increase the light chain diversity. Sequences of homology between the YAC and cosmid, which can be used for targeted integration, are the variable region genes and the vector sequences which originate from pBR. The cosmid vector pHC79 (8), contains the tetracycline (tet) resistance gene carrying a unique SailI restriction site which, being a relatively infrequent cutter of mammalian DNA, serves as a useful site for linearization. pYAC vectors (9) used for construction of large insert libraries also contain a portion of the tet gene carrying the unique SailI site. This 300 base pair region of homology allows the targeted insertion of the cosmid linearized with SailI, into the right (non-centromeric) YAC arm. Co-transfection of cosmid DNA together with the previously described vector pLUNA (6), containing yeast selectable marker genes URA3 and LYS2, and the mammalian neomycin resistance gene, allows selection in media lacking both lysine and uracil. Yeast colony hybridization of the subsequent transformants, using a cosmid specific probe, permits facile selection of YACs which have integrated cosmid DNA (Figure
Pharmacokinetic and pharmacodynamic evaluation of macitentan, a novel endothelin receptor antagonist for the treatment of pulmonary arterial hypertension

Introduction: Pulmonary arterial hypertension (PAH) is a chronic disorder of the pulmonary vasculature characterized by elevated mean pulmonary arterial pressure eventually leading to right-sided heart failure and premature death. Macitentan is an oral, once-daily, dual endothelin (ET)A and ETB receptor antagonist with high affinity and sustained receptor binding that was approved in the USA, Europe, Canada, and Switzerland for the treatment of PAH. Areas covered: This review discusses the pharmacokinetics (PK) and pharmacodynamics (PD) of macitentan and its drug interaction potential based on preclinical and clinical data. Expert opinion: Up to date, macitentan is the only registered treatment for PAH that significantly reduced morbidity and mortality as a combined endpoint in a long-term event-driven study. The safety profile of macitentan is favorable with respect to hepatic safety and edema/fluid retention and may be better than that of other ET receptor antagonists such as bosentan and ambrisentan. The PK profile supports a once-a-day dosing regimen. Macitentan has limited interactions with other drugs. Based on these characteristics macitentan is an important new addition to the treatment of PAH.
Learning to Score System Summaries for Better Content Selection Evaluation.

The evaluation of summaries is a challenging but crucial task of the summarization field. In this work, we propose to learn an automatic scoring metric based on the human judgements available as part of classical summarization datasets like TAC-2008 and TAC-2009. Any existing automatic scoring metrics can be included as features, the model learns the combination exhibiting the best correlation with human judgments. The reliability of the new metric is tested in a further manual evaluation where we ask humans to evaluate summaries covering the whole scoring spectrum of the metric. We release the trained metric as an open-source tool.
Equipped: overcoming barriers to change to improve quality of care (theories of change)

Quality improvement is about the patient; the child who comes to us to be cared for. It is our obligation to meet the needs of the child in a reliable way, to get care right the first time every time. Yet we often fail to achieve this. The key is to develop systems of care that will more than meet the rising expectations of the population. This article explores the complexity of change in healthcare, based on Deming's theories of change1 with practical ideas for introducing improvements in quality of care. In his review of safety in NHS England post Mid Staffordshire, Berwick2 recommended that “Mastery of quality and patient safety sciences and practices should be part of initial preparation and lifelong education of all health care professionals, including managers and executives”. This places a requirement on all of us to take the lead in quality initiatives. To achieve this duty, we require an understanding of the science of improvement and of theories of change. Despite the impressive clinical gains in the past years, the problems of waits, delayed diagnosis, harm and lack of equity remain. Healthcare professionals do not always provide evidence-based care for a variety of reasons, including lack of awareness, or scepticism of the validity of the data, beliefs derived from our own experiences and a perception of the individuality of patients. In addition, healthcare has become unaffordable in terms of waste and cost. Although we may be aware of what needs to change and how to go about it, introducing change can be extremely challenging. It may be difficult to convince doctors or organisations to do things differently. Clinical standards reflect the distillation of best evidence into guidelines that then are applied in the clinical environment. The National Institute for Health and Care Excellence …
Current and future health and economic impact of hepatitis C in Belgium.

BACKGROUND AND STUDY AIMS Chronic hepatitis C virus (HCV) infection is a serious global health problem affecting 150 million individuals worldwide. Although infection rates are decreasing, an aging population with progressing disease is expected to result in increased burden of advanced stage disease with high associated costs. This analysis describes the current and projected future economic impact of HCV sequelae in Belgium. METHODS A previously described and validated model was populated with Belgian inputs and calibrated to project the current and future health and economic burden of HCV. Monte Carlo and sensitivity analyses were run to quantify uncertainty. All estimates exclude the cost of antiviral therapy. RESULTS Costs associated with HCV were projected to peak in 2026 at Euro126M (Euro30M-Euro257M), while decompensated cirrhosis and hepatocellular carcinoma costs were projected to increase until 2031 and 2034. The projected 2014-2030 cumulative cost of HCV under current conditions was Euro1,850M. Scenarios to reduce the burden of HCV could result in Euro70M-Euro400M in cumulative cost savings. Starting treatment (1,000 patients) in 2015 could result in Euro150M cost savings. The lifetime cost of HCV increases with life expectancy, with highest future costs projected among young females with early stage disease. CONCLUSIONS The economic burden of HCV and advanced stage disease were projected to further increase. Cost reductions are possible with timely interventions aimed at minimizing the health burden of advanced stage disease.
Bottle Characteristics of Topical International Glaucoma Medications versus Local Brands in Saudi Arabia

What Is Known and Objective: Physical bottle characteristics differ of brand name topical glaucoma medications and local generic equivalents. This study compares the bottle characteristics of international topical glaucoma brands versus local brands from the Kingdom of Saudi Arabia. Methods: Data were collected on bottle drum volume, drop volume, bottle "squeezability," bottle tip diameter, labels and instructions, cap color coding, and clarity of the drug label. Density-based calculations of drops in bottle volume were assessed using an analytic balance. Bottle tip diameter was measured using 0.05 mm Vernier calipers. A Likert scale-based questionnaire was used to evaluate the subjective opinions of patients on bottle squeezability, clarity of usage and storage instructions, and the consistency of the cap color coding. Results: The volumes of international brands were statistically significantly higher than the local brands (P < 0.001). A number of drops per bottle and tip diameter were comparable between the international local brands. Cap color coding was inconsistent for international and local brands. Patients were dissatisfied with the label font size. Patients reported that the international and local brands were similar in terms of the ease of opening the bottle, instilling a drop, and the clarity of the instructions; but the local brands were subjectively easier to squeeze than international brands. What Is New and Conclusions: This is the first study to compare bottle characteristics of local Saudi Arabia brands with international brands. The bottle characteristics and patient feedback were similar between the local and international topical glaucoma medications. However, there were differences between the local and international brands in drug volume, bottle squeezability. Hence, patient compliance and drop dosage may differ based on the origin of manufacture.
Primary radiotherapy versus radical prostatectomy for high‐risk prostate cancer

Two evidence‐based therapies exist for the treatment of high‐risk prostate cancer (PCA): external‐beam radiotherapy (RT) with hormone therapy (H) (RT + H) and radical prostatectomy (S) with adjuvant radiotherapy (S + RT). Each of these strategies is associated with different rates of local control, distant metastasis (DM), and toxicity. By using decision analysis, the authors of this report compared the quality‐adjusted life expectancy (QALE) between men with high‐risk PCA who received RT + H versus S + RT versus a hypothetical trimodality therapy (S + RT + H).
Omalizumab Modulates Bronchial Reticular Basement Membrane Thickness and Eosinophil Infiltration in Severe Persistent Allergic Asthma Patients

Severe persistent asthma causes a substantial morbidity and mortality burden and is frequently not well controlled, despite intensive guideline-based therapy. The unique monoclonal antibody approved for patients with severe allergic asthma is omalizumab: a recombinant humanised murine against IgE antibodies. The aim of the present study is to investigate the effect of long-term anti-IgE on the thickening of the reticular basement membrane (RBM) and eosinophil infiltration in bronchial biopsies from patients with severe persistent allergic asthma. Biopsies were obtained from 11 patients with severe persistent allergic asthma before and after (12 months) treatment with omalizumab. RBM thickness and eosinophils were measured by using light microscope image analysis. A significant mean reduction in RBM thickness and eosinophil infiltration were measured after one-year omalizumab treatment. No correlation between eosinophil reduction and RBM thickness reduction was found. No correlation between each of the previous two parameters and clinical parameters was detected. In conclusion, our study showed that a substantial proportion of severe asthmatics reduced the original bronchial RBM thickness and eosinophil infiltration after one-year treatment with anti-IgE, thus emphasizing the possible role of omalizumab in affecting airway remodeling in severe persistent allergic asthma.
Representational Gaps, Team Integration and Team Creativity: The Mediating Roles of Conflict and Coordination

Functional diversity is central to the performance of product development teams in that multiple perspectives increase the team’s creativity. Failures in cross-functional product development teams (CFPDTs) are often attributed to a team’s inability to capitalize on their diversity. In this study we develop and test a model based on the representational gaps perspective (Cronin & Weingart, 2007a; Weingart, Cronin, Houser, Cagan, & Vogel, 2005) to determine factors that promote or limit creativity in CFPDTs. In particular we examine how representational gaps and cognitive and affective integration in CFPDTs affect coordination and conflict, which in turn influence the novelty and usefulness of the products designed. Furthermore, we investigate when conflict resulting from the representational gaps stimulates or harms creativity. We test these relationships using a path analysis on data across two time periods from cross-functional product development student teams. Representational gaps, affective integration, and cognitive integration were found to collectively improve team creativity via task conflict, relationship conflict, and coordination. Representational gaps and cognitive integration largely influenced creativity through task conflict, coordination, and conflict management. Affective integration operated via its effect on relationship conflict and an interactive effect with cognitive integration on task conflict. Furthermore, the effects of conflict and coordination on creativity depended on the conflict management approach used by the group. We discuss these findings in detail and end by considering the implications for the management of cross functional teams engaged in potentially creative work.