Miracle-dz/UniFAR-FTUs huggingface dataset:
Nonsense mutation in exon V of the factor XI gene does not abolish platelet factor XI expression

Factor XI (FXI) is a plasma glycoprotein produced by the liver that plays an essential role in blood coagulation. Individuals deficient in this protein are prone to bleeding following trauma or surgery. Well‐washed platelets possess FXI‐like activity and FXI antigen that differs in molecular weight from plasma FXI and is associated with FXI mRNA from platelets in which exon V is absent. Some individuals deficient in plasma FXI produce the platelet form of the protein. The molecular basis for the presence of platelet FXI in plasma FXI‐deficient patients is unknown. In the current study, to help determine the mechanism for this differential expression, the FXI genotype was determined for three plasma FXI‐deficient individuals who express platelet FXI. All three individuals had a nonsense mutation encoding a stop codon in exon V of the FXI gene that would result in a severely truncated polypeptide. An exon V nonsense mutation in the FXI gene combined with the absence of exon V in platelet FXI mRNA provides a plausible mechanism for the differential expression of platelet FXI in plasma FXI‐deficient patients.
Peripheral enhancement and spatial contrast uptake heterogeneity of primary breast tumours: quantitative assessment with dynamic MRI.

PURPOSE The purpose of our study was to determine if quantitative analysis of peripheral enhancement and spatial contrast uptake heterogeneity is useful in the characterisation of abnormalities seen at breast MRI. METHOD Ninety-one women underwent dynamic gadolinium-enhanced breast MRI. Regions of interest were processed by a parallel thinning algorithm to define central and peripheral subregions of lesions. Peripheral enhancement was quantified at every time point of the dynamic sequence as a signal difference-to-noise ratio. Moreover, a radiologist assessed the images for the presence of peripheral enhancement and classified the regional and subregional time-intensity profiles of each lesion. RESULTS Sixty-four invasive carcinomas and 30 benign lesions were analysed. Significant differences were found between benign and malignant lesions in peripheral enhancement as determined from the dynamic images (p = 0.0002; sensitivity, 0.34; specificity, 1.00) in time-intensity profiles (p < 0.000005; sensitivity, 0.67; specificity, 0.93) and in peripheral percentage signal changes at 1 min postcontrast (p = 0.001). There was a much higher relative signal increase centrally than peripherally (p < 0.0005), but peripheral signal changes had greater diagnostic value than central ones (Az = 0.72 vs. 0.63; p = 0.02). Carcinomas showed higher peripheral enhancement than benign lesions (p = 0.001). Peripheral enhancement reached maximum diagnostic value at 4 min postcontrast (Az = 0.80) and performed best as a highly sensitive but moderately specific diagnostic index. CONCLUSION Quantification of peripheral enhancement is diagnostically useful and offers insight into the enhancement mechanisms encountered in breast MRI. Primary breast tumours show substantial spatial contrast uptake heterogeneity. Lesion differentiation based on percentage signal changes is improved by restricting sampling to the periphery of tumours.
Response of parkinsonian swallowing dysfunction to dopaminergic stimulation

OBJECTIVES To determine the degree of dopaminergic response of swallowing dysfunction in Parkinson’s disease. METHODS Fifteen patients with idiopathic Parkinson’s disease and symptomatic dysphagia were studied. All had motor fluctuations in response to long term levodopa therapy. On two separate days, after overnight withdrawal of all antiparkinsonian medication, a modified barium swallow using cinefluoroscopy and different food consistencies was performed before and after administration of oral levodopa and subcutaneous apomorphine. RESULTS Despite all patients having an unequivocal motor response to both agents, there were few significant responses in any of the quantitative or qualitative criteria of swallowing dysfunction assessed. The oral preparatory phase, generally considered a more voluntary component of swallowing, showed a response, but not with all consistencies. In a subgroup of patients the pharyngeal phase time also improved. CONCLUSIONS These findings suggest that parkinsonian swallowing dysfunction is not solely related to nigrostriatal dopamine deficiency and may be due to an additional non-dopamine related disturbance of the central pattern generator for swallowing in the pedunculopontine nucleus or related structures in the medulla.
CCR4 and CXCR3 play different roles in the migration of T cells to inflammation in skin, arthritic joints, and lymph nodes

CCR4 and CXCR3 are expressed on several T‐cell subsets in inflamed tissues, yet their role in tissue‐specific recruitment is unclear. We examined the contributions of CCR4 and CXCR3 to T‐cell recruitment into inflamed joints in collagen‐induced arthritis, antigen‐draining lymph nodes (LNs) and dermal inflammatory sites (poly I:C, LPS, concanavalin A, and delayed type hypersensitivity), using labeled activated T cells from CXCR3−/−, CCR4−/−, and WT mice. Both CXCR3 and CCR4 deficiency reduced the development of arthritis, but did not affect Th1‐cell recruitment to the inflamed joints. Accumulation in inflamed LNs was highly CXCR3 dependent. In contrast, CCR4‐deficient Th1 cells had an increased accumulation in these LNs. Migration to all four dermal inflammatory sites by activated Th1 and T cytotoxic cells and memory CD4+ T cells was partially CXCR3‐dependent, but Treg‐cell migration was independent of CXCR3. The subset of cells expressing CCR4 has skin‐migrating properties, but CCR4 itself is not required for the migration. Thus, migration into these inflamed tissues is CCR4‐independent, and partially dependent on CXCR3, except for Treg cells, which require neither receptor. CCR4 may therefore affect retention of T cells in different tissues rather than trafficking out of the blood.
Expression of the neu proto‐oncogene by schwann cells during peripheral nerve development and wallerian degeneration

The neu gene, which encodes a putative tyrosine kinase growth factor receptor termed p185neu, was originally identified as a dominant transforming gene in neurogliomas and schwannomas induced by transplacental treatment of rat embryos with ethylnitrosourea. The present studies were undertaken to determine the expression pattern of the neu gene in peripheral nerve. Northern blot analysis of total RNA isolated from rat sciatic nerves demonstrated prominent neu mRNA expression on postnatal days 1 and 7, with substantially lower expression up to adulthood. Immunohistochemical studies confirmed expression of the p185neu by Schwann cells (SC) in developing sciatic nerve and minimal p185neu immunoreactivity in adult nerves. However, neu mRNA and p185neu Protein progressively increased following sciatic nerve transection in adult animals. In addition, neu mRNA and pl85neu were found in neonatal rat sciatic nerve SC and several SC‐derived cell lines. In resting SC, neu mRNA was expressed at a low level, but was greatly increased by treatment with forskolin and glial growth factor. These studies demonstrate that the neu gene and its protein product, p185neu, are expressed by SC both in vivo and in vitro and suggest that p185neu plays a role in the regulation of SC proliferation or differentiation.
Impact of screening on prostate cancer rates and trends

Widespread implementation of prostate cancer screening has affected several epidemiologic features of the disease including incidence, tumor and patient characteristics, patterns of care and outcomes. Some of these changes have been interpreted as evidence of the success of PSA testing as a cancer control strategy. Data are available from multiple sources to assess the association of early detection on recent prostate cancer rates and trends. National mortality data in the United States may be particularly informative because of the early and widespread adoption of PSA testing there. Incidence data from tumor registries and other regional resources are also relevant to this question. Case‐control analyses and modeling of relevant rates and trends have recently been reported. Multiple sources of data show that prostate cancer incidence rates rose following the introduction of PSA testing. The average age at diagnosis has fallen, the proportion of advanced stage tumors has declined, the proportion of moderately differentiated tumors has increased, and patterns of care have changed accordingly. A decline in mortality began in the United States in 1991. The decline in mortality is well established but this recent trend may only retrace an increase in mortality that immediately preceded. The descriptive epidemiology of prostate cancer reveals many effects of the introduction of prostate cancer screening. Although the evidence suggests increased prostate cancer testing has yielded public health benefit, this has not yet been shown conclusively. Microsc. Res. Tech. 51:415–418, 2000. © 2000 Wiley‐Liss, Inc.
Factors that Influence Femoral Neck Length. Analysis of 1543 Patients with Advanced Osteoarthritis of the Hip

Background and purpose There is little known about the relationship between patient characteristic and the variance in geometrical properties of the femoral neck. The length of the femoral neck is relevant when considering a femoral neck preserving hip replacement. Based on surgical experience we hypothesised that femoral neck length (FNL) decreased with age. We investigated whether certain patient characteristics were related to FNL and the femoral head diameter/FNL ratio. Patients and Methods The femoral neck length of 1543 patients with osteoarthritis grade 3 and 4 was measured on calibrated pelvic radiographs. Results Increasing age and height were associated positively, while increasing CCD angle and femoral head diameter were associated negatively with femoral neck length. Female gender and height were associated negatively and CCD angle positively with the femoral head diameter/FNL ratio. The FNL in 10 year older individuals was on average 0.2 mm (1%) longer. Moreover, every 10 extra degrees in CCD coincided with a neck length decrease of 1.5 mm (8%) in our population. Interpretation It seems justified to conclude that age is not a clinical relevant factor in the indication for femoral neck preserving hip arthroplasty. In this respect, CCD angle seems the most clinical relevant factor. Severe valgus angled hips are not a very suitable indication for femoral neck preserving prosthesis.
The Accuracy of Ultrasound, Stereotactic, and Clinical Core Biopsies in the Diagnosis of Breast Cancer, With an Analysis of False-Negative Cases

Objective:Preoperative core biopsy in breast cancer is becoming the standard of care. The aim of this study was to analyze the various methods of core biopsy with respect to diagnostic accuracy and to examine the management and outcome of those patients with false-negative biopsies. Methods:All patients undergoing core biopsy for breast abnormalities over a 5-year period (1999–2003) were reviewed. The accuracy rates for each method of core biopsy, the histologic agreement between the core pathology and subsequent excision pathology, and the length of follow-up for cases of benign disease were studied. Patients whose biopsies were benign but who were subsequently diagnosed with cancer underwent detailed review. Results:There were 2427 core biopsies performed over the 5-year period, resulting in a final diagnosis of cancer in 1384 patients, benign disease in 954 patients, and atypical disease in 89 patients. Biopsy type consisted of 1279 ultrasound-guided cores, 739 clinically guided cores, and 409 stereotactic-guided cores. The overall false-negative rate was 6.1%, with specific rates for ultrasound-, clinical-, and stereotactic-guided cores of 1.7%, 13%, and 8.9%, respectively. False-negative biopsies occurred in 85 patients, and in 8 of these patients the diagnosis was delayed by greater than 2 months. In all other false-negative cases, “triple assessment” review allowed prompt recognition of discordant biopsy results and further evaluation. Conclusion:Ultrasound guidance should be used to perform core biopsies in evaluating all breast abnormalities visible on ultrasound. Adherence to principles of triple assessment following biopsy allows for early recognition of the majority of false-negative cases.
WT1 expression in angiogenic tumours of the skin

Aims : To determine the expression of WT1 in endothelial proliferations and tumours. Endothelial cells are derived from angioblasts which differentiate into bone marrow stem cells (BMSC). BMSC are characterized by the constitutive expression of the WT1 gene and we have postulated that its expression may be maintained during the differentiation of angioblasts to endothelial cells.
'Leave me alone and let me teach.'Teachers’ views of Welsh Government education policies and education in Wales

The purpose of this article is twofold: firstly, to discuss what teachers in Wales think about the Welsh Government’s recent education (mainly school) policies and secondly, how the educational system in Wales might be improved. It is based on the findings from a general survey conducted by the Wales Institute of Social & Economic Research, Data & Methods (WISERD) Education. The views of 220 primary and secondary teachers and head teachers were gathered in 2014. The paper’s central theme is that teachers in Wales generally welcome policies with a strong element of social justice but believe that there have been too many educational initiatives over recent years. They think the educational system in Wales can be improved through various means, including: reducing bureaucracy, increasing their professional autonomy, developing quality professional development and clear leadership. The findings are limited by the nature of a small-scale survey but reinforce conclusions reached in other research studies in the United Kingdom, regarding teachers’ criticisms of the pace of curriculum change and initiative overload (Berliner, 2011; NUT, 2014) as well as general pointers towards more effective educational systems (OECD, 2014). For its part, the challenge for the Welsh Government is building consensus at a time when the performance of Welsh youngsters, relative to other countries, is poor.
Simulated Microgravity Induces Microvolt T Wave Alternans

Background: There are numerous anecdotal reports of ventricular arrhythmias during spaceflight; however, it is not known whether spaceflight or microgravity systematically increases the risk of cardiac dysrhythmias. Microvolt T wave alternans (MTWA) testing compares favorably with other noninvasive risk stratifiers and invasive electrophysiological testing in patients as a predictor of sudden cardiac death, ventricular tachycardia, and ventricular fibrillation. We hypothesized that simulated microgravity leads to an increase in MTWA.
Negative Temperature Dependence of a Gravity - A Reality

— Temperature dependence of force of gravitation is one of the fundamental problems of physics. This problem has got special value in connection with that the general theory of relativity, supposing the weakest positive influence of a body temperature on its weight, actually rejects an opportunity of measurement of negative influence of temperature on gravity in laboratory conditions. Really, the recognition of negative temperature dependence of gravitation, for example, means basic impossibility of achievement of a singularity («a black hole») at a gravitational collapse. Laboratory experiments with exact weighing the heated up metal samples, indicating negative influence temperatures of bodies on their physical weight are described. Influence of mistakes of measurements is analyzed. Calculations of distribution of temperature in volume of the bar, agreed with experimental data of time dependence of weight of samples are executed. The physical substantiation of negative temperature dependence of weight of the bodies, based on correlation of acceleration at thermal movement of micro-particles of a body and its absolute temperature, are given.
Mouse pelota gene (Pelo): cDNA cloning, genomic structure, and chromosomal localization

The pelota gene of Drosophila melanogaster encodes a protein which is included in cell cycle regulation. Mutations were found to result in spermatogenic arrest, female sterility and disturbances in the patterning of the eye. We have recently isolated and characterized cDNA clones coding for the human pelota gene (PELO). Here we describe the cloning of the murine pelota cDNA and gene (Pelo) that encodes a 385-amino-acid protein. The exon-intron structure of the gene, which contains three exons, was determined. Comparison of the mouse amino acid sequences with the human and Drosophila sequences revealed an overall high identity (96% and 70%, respectively). Northern blot analysis detected a 1.7-kb transcript in all tissues studied. Southern blot analyses revealed that the pelota gene is present as a single copy in the mouse genome. The mouse pelota gene (Pelo) was mapped to the distal end of chromosome 13, in a region that is homologous with a segment of human chromosome 5q11 containing the orthologous human gene. Cloning of the mouse gene is an important step to study the function of the pelota gene in mammals and to create a mouse model for this evolutionarily conserved gene.
Determinants of the intention to use condoms in a sample of French adolescents

ABSTRACT Objective To identify the determinants of the intention to use and actual use of condoms in a sample of French adolescents based on Ajzen's Theory of Planned Behaviour. Method Two-hundred-and-thirty French secondary-school students (mean age: 17.68 years; SD = 1.08) completed a questionnaire about condom use intention. Results ‘Perceived behavioural control’, ‘individual attitudes’, ‘subjective socio-cultural norms’ and ‘subjective norms of close friends and relatives’ are the main factors explaining 33% of variance of condom use intention. For girls, intention is essentially associated with perceived control, subjective norms (‘close friends and relatives’, and then, ‘socio-cultural norms’) and individual attitudes, whereas for boys, it is more closely linked to individual attitudes and to subjective socio-cultural norms. The best predictors of the intention to use a condom are perceived control and individual attitudes for girls while, for boys, individual attitudes come before perceived control. Conclusion In order to design effective programmes for prevention of sexually transmitted infections, the determinants of the intention to use condoms must be considered.
Proximal Compared with Distal Gastric Cancer: Multivariate Analysis of Prognostic Factors

The major determinants of the poor prognosis of the patients with proximal-third gastric cancer (proximal gastric cancer or PGC) when compared with that of patients with more distally located gastric tumors (distal gastric cancer or DGC) rely both on the more advanced age and tumor stage at the moment of clinical presentation and on the higher postoperative mortality for PGC patients. We reviewed hospital records of 707 patients with gastric cancer (187 with PGC and 520 with DGC) observed during the period 1981 through 1996 at the same surgical unit. Demographic and pathological data, type of treatment, and hospital morbidity and mortality rates were recorded. Univariate and multivariate survival analysis was used to calculate the 5-year survival probabilities with respect to the following clinical and pathological variables: age, sex, gross appearance according to Borrmann classification, histological type according to Lauren, stage of the disease, tumor location, and type of treatment. PGC was associated with more advanced tumor stage (P < 0.0001), older age (P = 0.039), and higher necessity of extended surgery (P < 0.0001) when compared with DGC. Hospital mortality was 9.6 and 5 per cent in PGC and DGC patients respectively (P = 0.033). Overall 5-year survival was 17.7 and 36.4 per cent in PGC and DGC patients (P < 0.0001): 35.9 versus 57.6% (P = 0.0001) and 3.7 versus 7.6 per cent (P = 0.03) after radical and palliative surgery respectively. At multivariate survival analysis proximal location was found to be independently associated (P = 0.0007) with poor survival. The multivariate model shows the proximal location as an independent predictor of lesser favorable outcome in gastric cancer. The major determinants of the poor prognosis of PGC with respect to DGC rely both on the more advanced age and tumor stage at the moment of clinical presentation and on the higher postoperative morbidity for PGC patients.
Scrutinizing a Policy of “Engagement Without Recognition”: US Requests for Diplomatic Actions With De Facto States

De facto states are conventionally perceived as illegal entities, usually ignored by the rest of the world and therefore also isolated and severely sanctioned in most cases. We investigate US foreign-policy engagement with Abkhazia, Nagorno-Karabakh, Northern Cyprus, Somaliland, and Transnistria and explore when, why, and how interactions between the United States and “places that do not exist” has taken place. This is done by extensively using WikiLeaks diplomatic cables from 2003– to 2010 as a primary information source. We assume that by engaging and not recognizing, the US has sought to increase its leverage and footprint in conflicts that somehow affect its national interests. This engagement approach is presumably most successful when targeted adversaries turn out to be agents of peace and stability, or when strategic calculus outweighs the rationale for the conventional treatment of sovereign anomalies.
Whole-body Magnetic Resonance Imaging in Inflammatory Arthritis: Systematic Literature Review and First Steps Toward Standardization and an OMERACT Scoring System

Objective. Whole-body magnetic resonance imaging (WB-MRI) is a relatively new technique that can enable assessment of the overall inflammatory status of people with arthritis, but standards for image acquisition, definitions of key pathologies, and a quantification system are required. Our aim was to perform a systematic literature review (SLR) and to develop consensus definitions of key pathologies, anatomical locations for assessment, a set of MRI sequences and imaging planes for the different body regions, and a preliminary scoring system for WB-MRI in inflammatory arthritis. Methods. An SLR was initially performed, searching for WB-MRI studies in arthritis, osteoarthritis, spondyloarthritis, or enthesitis. These results were presented to a meeting of the MRI in Arthritis Working Group together with an MR image review. Following this, preliminary standards for WB-MRI in inflammatory arthritides were developed with further iteration at the Working Group meetings at the Outcome Measures in Rheumatology (OMERACT) 2016. Results. The SLR identified 10 relevant original articles (7 cross-sectional and 3 longitudinal, mostly focusing on synovitis and/or enthesitis in spondyloarthritis, 4 with reproducibility data). The Working Group decided on inflammation in peripheral joints and entheses as primary focus areas, and then developed consensus MRI definitions for these pathologies, selected anatomical locations for assessment, agreed on a core set of MRI sequences and imaging planes for the different regions, and proposed a preliminary scoring system. It was decided to test and further develop the system by iterative multireader exercises. Conclusion. These first steps in developing an OMERACT WB-MRI scoring system for use in inflammatory arthritides offer a framework for further testing and refinement.