Miracle-dz/UniFAR-FTUs huggingface dataset:
Brain morphologic changes in early stages of psychosis: Implications for clinical application and early intervention

To date, a large number of magnetic resonance imaging (MRI) studies have been conducted in schizophrenia, which generally demonstrate gray matter reduction, predominantly in the frontal and temporo‐limbic regions, as well as gross brain abnormalities (e.g., a deviated sulcogyral pattern). Although the causes as well as timing and course of these findings remain elusive, these morphologic changes (especially gross brain abnormalities and medial temporal lobe atrophy) are likely present at illness onset, possibly reflecting early neurodevelopmental abnormalities. In addition, longitudinal MRI studies suggest that patients with schizophrenia and related psychoses also have progressive gray matter reduction during the transition period from prodrome to overt psychosis, as well as initial periods after psychosis onset, while such changes may become almost stable in the chronic stage. These active brain changes during the early phases seem to be relevant to the development of clinical symptoms in a region‐specific manner (e.g., superior temporal gyrus atrophy and positive psychotic symptoms), but may be at least partly ameliorated by antipsychotic medication. Recently, increasing evidence from MRI findings in individuals at risk for developing psychosis has suggested that those who subsequently develop psychosis have baseline brain changes, which could be at least partly predictive of later transition into psychosis. In this article, we selectively review previous MRI findings during the course of psychosis and also refer to the possible clinical applicability of these neuroimaging research findings, especially in the diagnosis of schizophrenia and early intervention for psychosis.
Perfect Matching Quad Layouts for Manifold Meshes

This paper introduces a new approach to automatically generate pure quadrilateral patch layouts on manifold meshes. The algorithm is based on a careful construction of a singularity graph of a given input frame field or a given periodic global parameterization. A pure quadrilateral patch layout is then derived as a constrained minimum weight perfect matching of that graph. The resulting layout is optimal relative to a balance between coarseness and geometric feature alignment. We formulate the problem of finding pure quadrilateral patch layouts as a global optimization problem related to a well‐known concept in graph theory. The main advantage of the new method is its simplicity and its computation speed. Patch layouts generated by the present algorithm are high quality and are very competitive compared to current state of the art.
The risk of myocardial infarction in patients with reduced activity of cytochrome P450 2C9

Objective The aim of the present follow-up study was to investigate whether the enzyme activity of the human cytochrome P450 (CYP) 2C9 isoenzyme is associated with myocardial infarction. Methods We investigated whether the variant alleles CYP2C9*2 and CYP2C9*3 or the use of CYP2C9 substrates or inhibitors was associated with an increased risk of myocardial infarction in 2210 men and 3534 women from the Rotterdam Study, a prospective population-based cohort study of individuals aged 55 years or older. Results In women, the use of CYP2C9 substrates or inhibitors was significantly associated with incident myocardial infarction with a hazard ratio of 2.48 (95% confidence interval: 1.55–3.96). Within the group of female carriers of a variant allele, the use of CYP2C9 substrates or inhibitors was associated with a fourfold increased risk of myocardial infarction (hazard ratio 3.86, 95% confidence interval: 1.93–7.75), as compared with non-use. Neither the use of CYP2C9 inhibitors or substrates nor the variant CYP2C9 alleles were associated with an increased risk of myocardial infarction in men. Conclusions Drugs that are metabolized by CYP2C9 increase the risk of myocardial infarction in women. This risk was even higher in women with allelic variants of CYP2C9 with reduced enzyme activity.
Mesenchymal stem cells restore CCl4‐induced liver injury by an antioxidative process

We have investigated BM (bone marrow)‐derived MSCs (mesenchymal stem cells) for the treatment of liver injury. It was hypothesized that MSC‐mediated resolution of liver injury could occur through an antioxidative process. After being injected with CCl4 (carbon tetrachloride), mice were injected with syngenic BM‐derived MSCs or normal saline. Oxidative stress activity of the MSCs was determined by the analysis of ROS (reactive oxygen species) and SOD (superoxide dismutase) activity. In addition, cytoprotective genes of the liver tissue were assessed by real‐time PCR and ARE (antioxidant‐response element) reporter assay. Up‐regulated ROS of CCl4‐treated liver cells was attenuated by co‐culturing with MSCs. Suppression of SOD by adding an SOD inhibitor decreased the effect of MSCs on injured liver cells. MSCs significantly increased SOD activity and inhibited ROS production in the injured liver. The gene expression levels of Hmox‐1 (haem oxygenase‐1), BI‐1 (Bax inhibitor‐1), HGF (hepatocyte growth factor), GST (glutathione transferase) and Nrf2 (nuclear factor‐erythoid 2 p45 subunit‐related factor 20), attenuated by CCl4, were increased up to basal levels after MSC transplantation. In addition, MSCs induced an ARE, shown by luciferase activity, which represented a cytoprotective response in the injured liver. Evidence of a new cytoprotective effect is shown in which MSCs promote an antioxidant response and supports the potential of using MSC transplantation as an effective treatment modality for liver disease.
The corticobasal syndrome–Alzheimer’s disease conundrum

Corticobasal syndrome (CBS), once thought to be pathognomonic for corticobasal degeneration pathology, is increasingly reported with various underlying pathologies. Alzheimer’s disease is one such pathology, also once believed to be unique for its clinical syndrome of dementia of the Alzheimer’s type. CBS is believed to result from topography of asymmetric parietofrontal cortical lesion involvement, rather than lesion subtype. However, this topographical pattern is strikingly different to that typically associated with AD for unclear reasons. This article will focus on CBS with underlying AD pathology (CBS-AD), and will review associated clinical, imaging and demographic factors. Predicting AD pathology is of marked interest as disease-modifying therapies loom on the horizon, with biomarkers and imaging research underway. By reviewing the literature for CBS-AD case reports and series and contrasting them with CBS with underlying corticobasal degeneration pathology cases, the article aims to examine factors that may predict AD pathology. How AD pathology may produce this clinical phenotype, rather than the prototype dementia of the Alzheimer’s type, will also be reviewed.
Downregulation of RIF1 Enhances Sensitivity to Platinum-Based Chemotherapy in Epithelial Ovarian Cancer (EOC) by Regulating Nucleotide Excision Repair (NER) Pathway

Background/Aims: Rap1 interacting factor 1 (RIF1) was deemed to be involved in replication timing regulation and DNA damage response. However, little is known about the role of RIF1 in malignancies. Thus, this study aimed to investigate whether the expression of RIF1 is relevant to the response of epithelial ovarian cancer (EOC) patients to cisplatin chemotherapy and its underlying mechanism. Methods: Immunohistochemistry was used for detecting the expression of RIF1 in 72 human ovarian cancer tissues followed by association analysis of RIF1 expression with patients’ responses to platinum-based chemotherapy. The survival analysis of ovarian patients based on platinum chemotherapy was analyzed using online databases. RNA interference of RIF1 was carried out in OVCAR3 and A2780 cell lines, to determine the effect of lacking RIF1 expression on cellular responses to cisplatin by using MTS assay. The nucleotide excision repair (NER) capacity of these cells was assessed by using host-cell reactivation and UV sensitivity assay. Western Blot analysis was carried out to determine the effect of RIF1 on the proteins of NER and apoptosis signaling pathway by using RIF1 knockdown cells. BALB/c nude mice model was used for detection of response to cisplatin in vivo. Results: RIF1 expression was significantly associated with the response of ovarian patients to platinum-based chemotherapy (P< 0.01). In cohorts from online databases, high expression of RIF1 was associated with higher mortality of EOC patients based on platinum chemotherapy (P < 0.01). RIF1 knockdown increased sensitivity to cisplatin in EOC in vitro and in vivo. Deletion of RIF1 impaired the NER activity by inhibiting the NER proteins in ovarian cancer cells. Besides, knockdown of RIF1 enhanced cisplatin-induced apoptosis. Conclusions: RIF1 plays an important role in regulating the expression of NER proteins, which in turn contributes to cellular response to cisplatin and EOC patients’ response to platinum-based chemotherapy. RIF1 knockdown also promotes cisplatin-induced apoptosis. RIF1 may serve as a novel biomarker for predicting platinum-based chemosensitivity and the prognosis of EOC patients.
Through the Looking Glass: Brexit, Free Movement and the Future

This article looks at some of the implications of Brexit for free movement of persons within the European Union, for both UK citizens and those from other EU Member States. It begins by briefly outlining the principle of free movement of persons, one of the four ‘fundamental freedoms’ set out in the EU Treaties since the Union's foundation. The next section looks at the reasons why free movement of persons became such a fundamental issue in the UK referendum on EU membership, focusing on the issues of jobs, labour standards and welfare. The article goes on to consider possible alternatives for the UK's relationship with the EU, post-Brexit, in terms of free movement of person rights. In the concluding section, the article considers the future of free movement of person rights within the EU itself.
Comparison of propofol and thiopentone as anaesthetic agents for electroconvulsive therapy

Propofol and thiopentone were compared as anaesthetic agents for electroconvulsive therapy in 31 patients on four occasions in a repeated measure crossover study. Discomfort on injection was significantly more common with propofol (51.6% of anaesthetics) compared to thiopentone (1.6% of anaesthetics). The duration of seizure was shorter with propofol in both treatments but there was significant drug‐time interaction. Propofol gave a milder tonus and clonus during seizure when both treatments were considered together. The increase in systolic and diastolic arterial pressures and heart rate after treatment were significantly higher with thiopentone. Apnoea was significantly longer with propofol. The times to sitting up unaided and opening the eyes on command were the same for both drugs. The ability to walk 10 m 20 minutes after anaesthesia was significantly better with propofol (p < 0.0001).
Does Family Involvement in Management Reduce the Risk of Business Failure? The Moderating Role of Entrepreneurial Orientation

This study explores the question of whether—and under which circumstances—family involvement helps avoid business failure. We hypothesize that it is family involvement in management, rather than ownership, which reduces the risk of failure during economic downturns; however, this effect is negatively affected by the firm’s entrepreneurial orientation (EO). We argue that EO hinders reaching consensuses on and commitment to family-centered goals, which are focused on long-term survival. We analyze 369 manufacturing firms in Spain from 2007 to 2013, and find that family involvement in management reduces the risk of business failure, but this effect decreases as EO increases.
Failing forward in EU migration policy? EU integration after the 2015 asylum and migration crisis

ABSTRACT By advancing integration through incomplete agreements, the European Union (EU) has created the very conditions for the emergence of crises, and this has, in turn, spurred on further agreements to deepen integration. Employing this theoretical lens, this article examines EU co-operation in asylum and migration that culminated in 2015 to determine whether crises are, in fact, integral to a cyclical process of EU integration rather than occasional events caused by external shocks. This is done by examining the failures and crises that emerged in migration and asylum policy up to 2015 and the agreements struck at EU level to address them. It is found that despite nominal action to address the weak monitoring mechanisms in use to date and incremental reinforcement of the constellation of institutions operating in this area, no solution has dealt with the critical lack of solidarity and absence of centralized institutions at the root of these issues.
Early induction of secretoneurin expression following kainic acid administration at convulsant doses in the rat and gerbil hippocampus

The expression of secretogranin‐II and its major proteolytic product secretoneurin (SN) is under the control of neuronal excitation, as demonstrated by treating rats with the excitotoxic kainic acid (KA). Differences in the structure and function of the hippocampus in rats and gerbils have been described; these suggest possible differential reactive responses to KA. In the present study, the SN immunostaining pattern in relation with cell damage is analyzed from 6 h to 4 days following KA administration in rats and gerbils.
Visual Arts Assessment in the Age of Educational Accountability.

Art teachers have, in some manner, always assessed student learning and progress. However, many art teachers do not have the training in assessment to be able to describe and defend their process, nor has there been research to support the effectiveness of how art teachers assess student learning. This study examines the ways six visual art teachers from five districts teaching in traditional public schools at the elementary, middle, and high school levels assess visual art. It demonstrates how they are using information gathered from assessments and whether their philosophies of art education influence their actions. Parents and administrators were also interviewed to gather their understanding of visual art assessment. I discuss changes in the way art teachers assess since accountability through Educator Effectiveness (CDE, 2015a) has become a focus of education and what these findings mean to art education in general. This is a qualitative study in the arts-based method of educational connoisseurship and criticism (Eisner, 1998b, 2002b, 2005). I interviewed and observed the teachers in their classrooms from the introduction to the completion of a work of art with their students. I report findings from each school in descriptive vignettes organized around Eisner’s ecology of schooling (Eisner 1998b, 2002a). From these I have identified themes, commonalities, and areas of divergence that present a way for art teachers to describe and justify how, what, and why they assess student learning and provide insight into the world of visual art assessment in the age of educational accountability. iii Table of
Solution Structure and DNA-binding Mode of the Matrix Attachment Region-binding Domain of the Transcription Factor SATB1 That Regulates the T-cell Maturation*

SATB1 is a transcriptional regulator controlling the gene expression that is essential in the maturation of the immune T-cell. SATB1 binds to the nuclear matrix attachment regions of DNA, where it recruits histone deacetylase and represses transcription through a local chromatin remodeling. Here we determined the solution structure of the matrix attachment region-binding domain, possessing similarity to the CUT DNA-binding domain, of human SATB1 by NMR spectroscopy. The structure consists of five α-helices, in which the N-terminal four are arranged similarly to the four-helix structure of the CUT domain of hepatocyte nuclear factor 6α. By an NMR chemical shift perturbation analysis and by surface plasmon resonance analyses of SATB1 mutant proteins, an interface for DNA binding was revealed to be located at the third helix and the surrounding regions. Surface plasmon resonance experiments using groove-specific binding drugs and methylated DNAs indicated that the domain recognizes DNA from the major groove side. These observations suggested that SATB1 possesses a DNA-binding mode similar to that of the POU-specific DNA-binding domain, which is known to share structural similarity to the four-helix CUT domain.
The Toxicity of Nanoparticles Depends on Multiple Molecular and Physicochemical Mechanisms

Nanotechnology is an emerging discipline that studies matters at the nanoscale level. Eventually, the goal is to manipulate matters at the atomic level to serve mankind. One growing area in nanotechnology is biomedical applications, which involve disease management and the discovery of basic biological principles. In this review, we discuss characteristics of nanomaterials, with an emphasis on transition metal oxide nanoparticles that influence cytotoxicity. Identification of those properties may lead to the design of more efficient and safer nanosized products for various industrial purposes and provide guidance for assessment of human and environmental health risk. We then investigate biochemical and molecular mechanisms of cytotoxicity that include oxidative stress-induced cellular events and alteration of the pathways pertaining to intracellular calcium homeostasis. All the stresses lead to cell injuries and death. Furthermore, as exposure to nanoparticles results in deregulation of the cell cycle (i.e., interfering with cell proliferation), the change in cell number is a function of cell killing and the suppression of cell proliferation. Collectively, the review article provides insights into the complexity of nanotoxicology.
Finger doses received by raediologists during Chiba needle percutaneous cholangiography.

In a previous communication we have drawn attention to the possibility of an excessive radiation dose to the radiologist's fingers during percutaneous transhepatic cholangiography (PTC) using the Chiba technique, unless the fluoroscopy diaphragms are coned down (Fraser et al., 1978). In these initial measurements using TLD monitors, we found that one of us whom we designated radiologist “A” received a dose-rate of 0.94 mSv/min (94 mrem/min) whereas a second radiologist whom we designated radiologist “B” received a dose-rate of 0.28 mSv/min (28 mrem/min), less than one-third of that received by radiologist “A”. The dose-rate to radiologist “B” agreed closely with an ion chamber measurement of 0.24 mSv/min (24 mrem/min). We ascribed this difference to the size of the aperture of the screening diaphragms; radiologist “A” coned the diaphragms only to the edge of the television screen, whereas radiologist “B” coned to a field about 10 × 10 cm. Because of the expeoted work load it seemed possible that the finge.
The Present and Future of Appointment, Tenure, and Compensation Policies for Medical School Clinical Faculty

The authors present data and information about appointment, tenure, and compensation policies to describe how medical schools are redefining the terms under which they relate to their full-time clinical faculties. First, the authors note the increasing differentiation of clinical faculty members into two groups, researchers and clinicians. The present-day competitive realities of both research and clinical enterprises have prompted this change and the principles of mission-based management are reinforcing it. Second, they document the long-term tendency of schools to appoint new clinical faculty members to contract-term (as opposed to tenure) appointments, as special non-tenure-eligible tracks for clinically oriented faculty proliferate. Third, they report on the policies of schools to limit the financial guarantees provided to clinical faculty members who are awarded tenure. For schools that have yet to address this issue, they discuss the various employment and pay arrangements that inform or confuse the question. Fourth, they describe historic problems with clinical faculty compensation arrangements and illustrate, with examples from ten schools, the characteristics of recently implemented performance- and risk-based compensation plans. While these trends in institutional policies and practices may initially concern faculty advocate groups, the authors argue that they may serve the long-term interests of those groups. The terms of relationships between medical schools and their clinical faculties are tied closely to the specifics of organizational structure, which are currently undergoing review and change. The challenge all schools face is to define these terms in ways that allow them to continue to attract high-quality clinical faculty while avoiding an insupportable financial liability.
In Vitro Inhibition of Hepadnavirus Polymerases by the Triphosphates of BMS-200475 and Lobucavir

ABSTRACT The guanosine analogs BMS-200475 and lobucavir have previously been shown to effectively suppress propagation of the human hepatitis B virus (HBV) and woodchuck hepatitis virus (WHV) in 2.2. 15 liver cells and in the woodchuck animal model system, respectively. This repression was presumed to occur via inhibition of the viral polymerase (Pol) by the triphosphate (TP) forms of BMS-200475 and lobucavir which are both produced in mammalian cells. To determine the exact mode of action, BMS-200475–TP and lobucavir-TP, along with several other guanosine analog-TPs and lamivudine-TP were tested against the HBV, WHV, and duck hepatitis B virus (DHBV) polymerases in vitro. Estimates of the 50% inhibitory concentrations revealed that BMS-200475–TP and lobucavir-TP inhibited HBV, WHV, and DHBV Pol comparably and were superior to the other nucleoside-TPs tested. More importantly, both analogs blocked the three distinct phases of hepadnaviral replication: priming, reverse transcription, and DNA-dependent DNA synthesis. These data suggest that the modest potency of lobucavir in 2.2. 15 cells may be the result of poor phosphorylation in vivo. Kinetic studies revealed that BMS-200475–TP and lobucavir-TP competitively inhibit HBV Pol and WHV Pol with respect to the natural dGTP substrate and that both drugs appear to bind to Pol with very high affinities. Endogenous sequencing reactions conducted in replicative HBV nucleocapsids suggested that BMS-200475–TP and lobucavir-TP are nonobligate chain terminators that stall Pol at sites that are distinct yet characteristically two to three residues downstream from dG incorporation sites.
‘So you row, do you? You don’t look like a rower.' An account of medical students' experience of sexism

Introduction Medicine has traditionally been considered a masculine pursuit and its undergraduate curriculum criticised as being inherently sexist. Overt sexism, though diminished, still occurs and students report offensive sexual remarks, unwanted sexual advances and unequal learning opportunities. Sexual discrimination also colludes with attitudes that promote the stereotyping of the roles of women both in medicine and in society itself. This study aimed to ascertain medical students' own experience of sexism during undergraduate training, their understanding of these events, what effects the events had on them and, specifically, how they coped.