Miracle-dz/UniFAR-FTUs huggingface dataset:
High‐field magnetic resonance imaging of brain iron: birth of a biomarker?

The brain has an unusually high concentration of iron, which is distributed in an unusual pattern unlike that in any other organ. The physiological role of this iron and the reasons for this pattern of distribution are not yet understood. There is increasing evidence that several neurodegenerative diseases are associated with altered brain iron metabolism. Understanding these dysmetabolic conditions may provide important information for their diagnosis and treatment. For many years the iron distribution in the human brain could be studied effectively only under postmortem conditions. This situation was changed dramatically by the finding that T2‐weighted MR imaging at high field strength (initially 1.5 T) appears to demonstrate the pattern of iron distribution in normal brains and that this imaging technique can detect changes in brain iron concentrations associated with disease states. Up to the present time this imaging capability has been utilized in many research applications but it has not yet been widely applied in the routine diagnosis and management of neurodegenerative disorders. However, recent advances in the basic science of brain iron metabolism, the clinical understanding of neurodegenerative diseases and in MRI technology, particularly in the availability of clinical scanners operating at the higher field strength of 3 T, suggest that iron‐dependent MR imaging may soon provide biomarkers capable of characterizing the presence and progression of important neurological disorders. Such biomarkers may be of crucial assistance in the development and utilization of effective new therapies for Alzheimer's and Parkinson's diseases, multiple sclerosis and other iron‐related CNS disorders which are difficult to diagnose and treat. Copyright © 2004 John Wiley & Sons, Ltd.
How to Incorporate Accident Severity and Vehicle Occupancy into the Hot Spot Identification Process?

This paper introduces a Bayesian accident risk analysis framework that integrates accident frequency and its expected consequences into the hot spot identification process. The Bayesian framework allows the introduction of uncertainty not only in the accident frequency and severity model parameters but also in key variables such as vehicle occupancy levels and severity weighting factors. For modeling and estimating the severity levels of each individual involved in an accident, a Bayesian multinomial model is proposed. For modeling accident frequency, hierarchical Poisson models are used. How the framework can be implemented to compute alternative relative and absolute measures of total risk for hot spot identification is described. To illustrate the proposed approach, a group of highway–railway crossings from Canada is used as an application environment.
MicroRNA-375 inhibits tumour growth and metastasis in oesophageal squamous cell carcinoma through repressing insulin-like growth factor 1 receptor

Background To understand the involvement of micro-RNA (miRNA) in the development and progression of oesophageal squamous cell carcinoma (ESCC), miRNA profiles were compared between tumour and corresponding non-tumour tissues. Methods miRCURY LNA array was used to generate miRNA expressing profile. Real-time quantitative PCR was applied to detectthe expression of miR-375 in ESCC samples and its correlation with insulin-like growth factor 1 receptor (IGF1R). Methylation-specific PCR was used to study the methylation status in the promoter region of miR-375. The tumour-suppressive effect of miR-375 was determined by both in-vitro and in-vivo assays. Results The downregulation of miR-375 was frequently detected in primary ESCC, which was significantly correlated with advanced stage (p=0.003), distant metastasis (p<0.0001), poor overall survival (p=0.048) and disease-free survival (p=0.0006). Promoter methylation of miR-375 was detected in 26 of 45 (57.8%) ESCC specimens. Functional assays demonstrated that miR-375 could inhibit clonogenicity, cell motility, cell proliferation, tumour formation and metastasis in mice. Further study showed that miR-375 could interact with the 3′-untranslated region of IGF1R and downregulate its expression. In clinical specimens, the expression of IGF1R was also negatively correlated with miR-375 expression (p=0.008). Conclusions This study demonstrates that miR-375 has a strong tumour-suppressive effect through inhibiting the expression of IGF1R. The downregulation of miR-375, which is mainly caused by promoter methylation, is one of the molecular mechanisms involved in the development and progression of ESCC.
Role of the coinhibitory receptor cytotoxic T lymphocyte antigen‐4 on apoptosis‐Prone CD8 T cells in persistent hepatitis B virus infection

An excess of coinhibitory signals has been proposed to drive the T‐cell exhaustion characteristic of persistent viral infections. In this study we examined the contribution of the coinhibitory receptor cytotoxic T lymphocyte antigen‐4 (CTLA‐4) to CD8 T cell tolerance in chronic hepatitis B virus (HBV) infection (CHB). CD8 T cells in patients with CHB have an increased propensity to express the coinhibitory receptor CTLA‐4 and this correlates with viral load. CTLA‐4 is up‐regulated on those HBV‐specific CD8 T cells with the highest levels of the proapoptotic protein Bim, which we have previously shown mediates their premature attrition; abrogation of CTLA‐4‐mediated coinhibition can reduce Bim expression. Longitudinal study of CHB patients beginning antiviral therapy reveals that HBV DNA suppression induces transient reconstitution of HBV‐specific CD8 T cells but does not reprogram their CTLA‐4hiBimhi tolerogenic phenotype. Blocking CTLA‐4 is able to increase the expansion of interferon gamma (IFN‐γ)‐producing HBV‐specific CD8 T cells in both the peripheral and intrahepatic compartments. The rescue of anti‐HBV responses by either CTLA‐4 or PD‐L1 blockade is nonredundant. Conclusion: CTLA‐4 is expressed by HBV‐specific CD8 T cells with high levels of Bim and helps to drive this proapoptotic phenotype. CTLA‐4 blockade could form one arm of a therapeutic approach to modulate the diverse patterns of coregulation of T‐cell exhaustion in this heterogeneous disease. (HEPATOLOGY 2011;)
Case stacking below the surface: On the possessor case alternation in Udmurt

Abstract In this paper we investigate the case split on the possessor in Udmurt. Traditionally, the choice between ablative and genitive possessor case is said to be driven by the grammatical function (GF) of the XP containing the possessor. We argue that the case split is not driven by GFs; rather, it is determined by the case value of the XP that contains the possessor. Importantly, there is no evidence which points to a possessor raising analysis in Udmurt. Instead, we present an analysis according to which the possessor always bears genitive but may be assigned another structural case by an external head. Due to a morphological constraint, stacked case features fuse into a single feature set in the postsyntactic morphological component. If accusative and genitive stack on the possessor, only the default semantic case marker, i.e., the ablative marker, can realize the resulting feature set. In any other context the genitive marker is chosen. We thus claim that there is no abstract ablative on the possessor; instead, the morphological ablative marker realizes a combination of two abstract structural cases.
BRCA mutation frequency and patterns of treatment response in BRCA mutation-positive women with ovarian cancer: a report from the Australian Ovarian Cancer Study Group.

PURPOSE The frequency of BRCA1 and BRCA2 germ-line mutations in women with ovarian cancer is unclear; reports vary from 3% to 27%. The impact of germ-line mutation on response requires further investigation to understand its impact on treatment planning and clinical trial design. PATIENTS AND METHODS Women with nonmucinous ovarian carcinoma (n = 1,001) enrolled onto a population-based, case-control study were screened for point mutations and large deletions in both genes. Survival outcomes and responses to multiple lines of chemotherapy were assessed. RESULTS Germ-line mutations were found in 14.1% of patients overall, including 16.6% of serous cancer patients (high-gradeserous, 17.1%); [corrected] 44% had no reported family history of breast orovarian cancer.Patients carrying germ-line mutations had improved rates of progression-free and overall survival. In the relapse setting, patients carrying mutations more frequently responded to both platin- and nonplatin-based regimens than mutation-negative patients, even in patients with early relapse after primary treatment. Mutation-negative patients who responded to multiple cycles of platin-based treatment were more likely to carry somatic BRCA1/2 mutations. CONCLUSION BRCA mutation status has a major influence on survival in ovarian cancer patients and should be an additional stratification factor in clinical trials. Treatment outcomes in BRCA1/2 carriers challenge conventional definitions of platin resistance, and mutation status may be able to contribute to decision making and systemic therapy selection in the relapse setting. Our data, together with the advent of poly(ADP-ribose) polymerase inhibitor trials, supports the recommendation that germ-line BRCA1/2 testing should be offered to all women diagnosed with nonmucinous, ovarian carcinoma, regardless of family history.
Genome complexity of methanogenic bacteria

The genome complexities of different methanogenic bacteria were investigated by using an optical method to study renaturation kinetics of single-stranded DNA. The observed genome sizes ranged from 1.0 X 10(9) to 1.8 X 10(9) daltons, which is a typical range for procaryotic cells. Melting profiles of the DNA of three methanogenic species from different families show fractions which have a higher A . T content than the average DNA of that species.
Coherence

The ability to understand and produce coherent text structure was assessed across three groups of college writers, normally achieving, learning disabled, and underprepared. It was found that college writers with learning disabilities were more like the normally achieving writers on an assessment of comprehension of text structure. On the production of a coherent text, normally achieving writers performed better than either of the other groups, but the writers with learning disabilities (LD) performed better than the underprepared writers. These results suggest that the writers with LD demonstrate greater discrepancies between their comprehension and production of written form than either of the other groups. The writers with LD appear to understand text structure like normally achieving writers but, like the underprepared writers, they experience difficulty in the production processes.
Influence of prepartum antibiotic therapy on intramammary infections in primigravid heifers during early lactation.

Jersey heifers were assigned alternately to three groups: 1) negative control (n = 41), 2) intramammary infusion of 200 mg of sodium cloxacillin (n = 38) at 7 d before expected parturition, and 3) intramammary infusion of 200 mg of cephapirin sodium (n = 36) at 7 d before expected parturition. The percentage of mammary glands infected prior to treatment was 62.2, 50.0, and 70.1 for groups 1, 2, and 3, respectively. The percentage of mammary glands infected during early lactation was 44.5, 8.6, and 2.1 for groups 1, 2, and 3, respectively. Most infections (87.1%) were due to Staphylococcus species other than Staphylococcus aureus. Thirty-six of 460 quarters were infected with major pathogens before treatment, 3 of 22 persisted following antibiotic treatment, and 9 of 14 persisted in the control group. Infusion of sodium cloxacillin resulted in antibiotic residues in 17.4% of samples obtained . 5 d postpartum. All samples were negative at 3 and 10 d postpartum. Infusion of cephapirin sodium resulted in antibiotic residues in 84.7, 28.2, and 0% of samples obtained at . 5, 3, and 10 d, respectively. Prepartum antibiotic therapy was effective in eliminating many IMI, especially those caused by coagulase-negative staphylococci, but there is the potential for antibiotic residues in milk.
Mutations in five loci affecting GAP1‐independent uptake of neutral amino acids in yeast

In order to identify genes involved in uptake of isoleucine, leucine and valine in Saccharomyces cerevisiae we isolated mutants that, on a complex medium, were sensitive to an inhibitor of the biosynthesis of the branched‐chain amino acids. Mutants that in a secondary screen showed reduced uptake of isoleucine, leucine and valine when growing in synthetic complete medium were further characterized. Genetic analysis identified five loci, named ssy1 through ssy5. ssy2 corresponds to the previously characterized bap1 mutation, which we recently have found to be allelic to stp1. ssy1, ssy3 and ssy5 exhibit a reduced uptake of phenylalanine, methionine and threonine, as well. Furthermore, they are resistant to several neutral amino acid analogs. ssy4 only affects uptake of few neutral amino acids and is as sensitive as the wild type to the amino acid analogs tested. It was previously found that a C‐terminal truncation of 29 codons of BAP2, which encodes a branched‐chain amino acid permease, results in increased uptake of the branched‐chain amino acids. We find epistasis of the C‐terminally truncated BAP2 gene over the ssy4 mutation, while the other ssy mutations are epistatic over the truncated BAP2 gene. SSY1, SSY3 and SSY5 were cloned from a low‐copy genomic library by complementation of the mutants. The SSY3 gene and the SSY5 gene show no significant homology to any sequence in the databases. SSY1 is a member of the major family of genes encoding amino acid permeases in yeast. We discuss possible roles of Ssy1p in amino acid uptake. © 1998 John Wiley & Sons, Ltd.
Authentication of bee pollen grains in bright‐field microscopy by combining one‐class classification techniques and image processing

A novel method for authenticating pollen grains in bright‐field microscopic images is presented in this work. The usage of this new method is clear in many application fields such as bee‐keeping sector, where laboratory experts need to identify fraudulent bee pollen samples against local known pollen types. Our system is based on image processing and one‐class classification to reject unknown pollen grain objects. The latter classification technique allows us to tackle the major difficulty of the problem, the existence of many possible fraudulent pollen types, and the impossibility of modeling all of them. Different one‐class classification paradigms are compared to study the most suitable technique for solving the problem. In addition, feature selection algorithms are applied to reduce the complexity and increase the accuracy of the models. For each local pollen type, a one‐class classifier is trained and aggregated into a multiclassifier model. This multiclassification scheme combines the output of all the one‐class classifiers in a unique final response. The proposed method is validated by authenticating pollen grains belonging to different Spanish bee pollen types. The overall accuracy of the system on classifying fraudulent microscopic pollen grain objects is 92.3%. The system is able to rapidly reject pollen grains, which belong to nonlocal pollen types, reducing the laboratory work and effort. The number of possible applications of this authentication method in the microscopy research field is unlimited. Microsc. Res. Tech. 2012. © 2012 Wiley Periodicals, Inc.
An Audience–Channel–Message–Evaluation (ACME) Framework for Health Communication Campaigns

Recent reviews of the literature have indicated that a number of health communication campaigns continue to fail to adhere to principles of effective campaign design. The lack of an integrated, organizing framework for the design, implementation, and evaluation of health communication campaigns may contribute to this state of affairs. The current article introduces an audience–channel–message–evaluation (ACME) framework that organizes the major principles of health campaign design, implementation, and evaluation. ACME also explicates the relationships and linkages between the varying principles. Insights from ACME include the following: The choice of audience segment(s) to focus on in a campaign affects all other campaign design choices, including message strategy and channel/component options. Although channel selection influences options for message design, choice of message design also influences channel options. Evaluation should not be thought of as a separate activity, but rather should be infused and integrated throughout the campaign design and implementation process, including formative, process, and outcome evaluation activities. Overall, health communication campaigns that adhere to this integrated set of principles of effective campaign design will have a greater chance of success than those using principles idiosyncratically. These design, implementation, and evaluation principles are embodied in the ACME framework.
Changes in glutamine and glutamate concentrations for tracking training tolerance.

PURPOSE The purpose was to monitor high-performance athletes throughout training macrocycles and competitions and examine the changes in plasma glutamine (Gm) and glutamate (Ga) concentrations in order to develop a model of tolerance to training. METHODS Plasma glutamine and glutamate concentrations of 52 National team athletes (31 male and 21 female) divided into male and female groups of speed skating, swimming, and cross-country skiing were measured in an early season rested condition to determine highest Gm and lowest Ga concentrations and over 2-4 macrocycles, which included heavy training to establish lowest Gm and highest Ga concentrations. RESULTS In the rested condition, there were no differences within and between the male and female groups, excluding five athletes (OTA) who became overtrained in heavy training. The mean (+/-SD) Gm concentration was 585 +/- 54 micromol x L(-1), Ga concentration 101 +/- 16 micromol x L(-1), and Gm/Ga ratio 5.88 +/- 0.84 micromol x L(-1). The OTA had a significantly higher Ga concentration of 128 +/- 16 micromol x L(-1) and lower Gm/Ga ratio of 4.43 +/- 0.49 micromol x L(-1) than all the other groups. In heavy training, there was a significant decrease (P < 0.05) in Gm concentration to 522 +/- 53 micromol x L(-1), significant increase in Ga concentration to 128 +/- 19 micromol x L(-1) and significant decrease in Gm/Ga ratio to 4.15 +/- 0.57 micromol x L(-1). The OTA Gm concentration of 488 +/- 31 micromol x L(-1) was significant lower than only the male speed skating and swimming groups. However, the Ga concentration of 171 +/- 17 micromol x L(-1) and Gm/Ga ratio of 2.88 +/- 0.27 micromol x L(-1) were significantly higher and lower respectively than all other groups. CONCLUSIONS Based on the changes in Gm and Ga concentration under different training conditions, we propose an athlete tolerance to training model where glutamine concentration reflects tolerance to volume of work and glutamate concentration reflects tolerance to high intensity training. We suggest that the Gm/Ga ratio may globally represent overall tolerance to training.
Metastases from cancer of the prostate. Autopsy and roentgenological findings

REVIEW OF THE RECORDS at the Pondville A Hospital for a twenty-year period (1928 through 1948) disclosed 437 cases of cancer of the prostate, the diagnosis having been made clinically or at autopsy. There were 199 who died at Pondville and autopsy findings are available in 148 cases. Of the 148, fortyfour were cases in which the prostatic carcinoma was only an incidental finding at postmortem examination, the patient having died of other causes, usually cancers elsewhere. There are thus 104 patients in whom a diagnosis of prostatic cancer had been made clinically and confirmed at autopsy. This group of 104 patients has been analyzed primarily in respect to metastatic spread as seen at postmortem, as well as to the discovery of metastasis by premortem roentgenray examination. In seven cases the neoplasm was still confined to the prostate, and in nine others the disease, although beyond the confines of the prostate, was still within the pelvis, i.e., had extended to the bladder, rectum, seminal vesicles, pelvic soft tissues, or to pelvic lymph nodes. In the other eighty-eight patients (85 per cent) there were distant metastases. The sites of the metastases in the 104 autopsied patients are listed in Table 1 (central nervous system not included). More than one third of the patients showed spread to the lungs, next in freqency to the most common site, the osseous system. As in other series the most common visceral metastases were to the liver and the lungs, with the adrenals and the pleura being next in frequency. Lymph-node involvement is indicated in Table 2. As expected, the pelvic nodes showed the greatest frequency of metastatic disease. In addition to widespread metastases, many of the cases had spread by direct extension to neighboring structures (Table 3). Growth into the bladder was about three times more common than to the rectum.
Topical Cyclosporin A in the treatment of acute graft rejection: a randomized controlled trial

Background: Corneal graft rejection is the commonest cause of graft failure. Currently, intensive topical steroid is the treatment for graft rejection. We hypothesized that the use of topical Cyclosporin A (CsA) 0.05%, specifically Restasis (Allergan) in addition to intensive steroids would aid in the reversal and treatment of endothelial graft rejection.
Determinants of physical activity and sedentary behaviour in young people: a review and quality synthesis of prospective studies

Objective The aim of this systematic review was to summarise and update the existing literature on determinants of physical activity and sedentary behaviour in young people, considering the methodological quality of the studies. Methods Prospective studies were identified from searches in PubMed and PsycINFO, from April 2004 through November 2010. The authors included studies investigating the association between determinants of overall physical (in)activity and/or sedentary behaviour in healthy children or adolescents. When a determinant was investigated for its association with physical (in)activity and sedentary behaviour assessed between ages of 4–12, or mean age ≤12, it was classified as ‘child determinant’. When a determinant was investigated for its association with physical activity and sedentary behaviour assessed between ages of 13–18 or mean age >12, it was classified as ‘adolescent determinant’. Included articles were scored on their methodological quality and a best-evidence synthesis was applied to summarise the results. Results The authors identified 30 papers, of which seven were of high methodological quality. Intention was found as a determinant of children's physical activity. Determinants of adolescents' physical activity were age (ie, older children were more active), ethnicity (ie, being of African–American descent determined being less physically active) and planning. The authors found insufficient evidence for determinants of sedentary behaviour. Conclusion Studies on determinants of physical activity and sedentary behaviour were in general of poor methodological quality. To develop long-term effective interventions that increase physical activity and decrease time spent in sedentary behaviours in young people, we need more high quality prospective evidence on the determinants of these behaviours.