Miracle-dz/UniFAR-FTUs huggingface dataset:
Increased expression of vascular cell adhesion molecule 1 in muscle biopsy samples from juvenile dermatomyositis patients with short duration of untreated disease is regulated by miR-126.

OBJECTIVE To evaluate the effect of duration of untreated disease on vascular cell adhesion molecule 1 (VCAM-1) and microRNA (miRNA) expression in muscle biopsy samples from children with juvenile dermatomyositis (DM) as well as its effect on soluble VCAM-1 (sVCAM-1) and tumor necrosis factor α (TNFα) concentrations in sera from these children. METHODS We enrolled 28 untreated children with juvenile DM and 8 pediatric controls. Eleven children with juvenile DM had short duration of untreated disease (symptoms for ≤2 months before muscle biopsy), and 17 had long duration of untreated disease (symptoms for >2 months before muscle biopsy). Vascular structures, characterized by immunofluorescence using antibodies against von Willebrand factor, VCAM-1, and α-smooth muscle actin, were measured for total area and intensity. Circulating sVCAM-1 and TNFα levels were determined in patients with short duration of untreated disease, patients with long duration of untreated disease, and controls. Differential expression of microRNA-126 (miR-126) in muscle biopsy samples from the 2 patient groups and the control group was detected by miRNA expression profiling and confirmed by quantitative reverse transcription-polymerase chain reaction in muscle biopsy samples from the 3 groups. RESULTS Juvenile DM patients with short duration of untreated disease had significantly higher total positive area and intensity/high power field of VCAM-1 expression than did juvenile DM patients with long duration of untreated disease (P = 0.043 and P = 0.015, respectively) or controls (P = 0.004 and P = 0.001, respectively). Von Willebrand factor antigen-positive vasculature displayed greater VCAM-1 intensity in patients with short duration of untreated disease than in patients with long duration of untreated disease (P = 0.001). Circulating levels of sVCAM-1 and TNFα were significantly higher in patients with short duration of untreated disease than in controls (P = 0.013 and P = 0.048, respectively). The miRNA miR-126, a negative regulator of VCAM-1 expression, was significantly decreased (3.39-fold; P < 0.006) in patients with short duration of untreated disease compared to controls, while miR-126 expression in patients with long duration of untreated disease did not differ significantly compared to controls. CONCLUSION In patients with short duration of untreated disease, miR-126 down-regulation is associated with increased VCAM-1 in both muscle and blood, suggesting that VCAM-1 plays a critical role early in juvenile DM disease pathophysiology, augmented by TNFα.
Prospective evaluation of frequency and nature of transcranial high-intensity Doppler signals in prosthetic valve recipients.

BACKGROUND AND AIM OF THE STUDY In asymptomatic prosthetic valve recipients, high-intensity transient signals (HITS) observed with transcranial Doppler (TCD) are a phenomenon of obscure clinical relevance which nature has not yet been elucidated convincingly. METHODS Eighty-three patients without carotid disease, history of cerebrovascular accidents, and with negative preoperative TCD undergoing either valve replacement (mitral, n = 11; aortic, n = 56; mitral + aortic, n = 6; 40 mechanical prostheses, 29 biological prostheses, 10 homografts) or mitral repair (n = 10) were evaluated prospectively by means of TCD at discharge, three months and one year after surgery, to analyze the presence, incidence and characteristics of HITS. Furthermore, in 12 patients positive for HITS, TCD was repeated during a 30-min period of 100% O2 inhalation. RESULTS Twenty-five patients (30%) were positive for HITS at all postoperative controls, although no neurological symptoms were observed. Mechanical prostheses showed a significantly higher incidence of HITS (85%) than biological prostheses (10%, p <0.001), repaired mitral valves (0%, p <0.001) and homografts (0%, p <0.001). At multivariate analysis the presence of a mechanical prosthesis was the only significant predictor of detection of HITS after valve replacement. During O2 inhalation, a significant decrease in the number of HITS per hour (55 +/- 79 versus 22 +/- 31, p = 0.002) occurred, which returned to initial values when room-air breathing was resumed. CONCLUSIONS Prosthetic valve replacement, particularly when mechanical devices are used, is associated with the generation of HITS which persist throughout the follow up period, but remain clinically silent. The decrease of HITS during O2 inhalation strongly supports the hypothesis of the gaseous nature of such signals and confirms the validity of this method in helping to differentiate gaseous microemboli from solid microemboli in prosthetic valve recipients.
Radioactive Decays in Geant4

The simulation of radioactive decays is a common task in Monte-Carlo systems such as Geant4. Usually, a system either uses an approach focusing on the simulations of every individual decay or an approach which simulates a large number of decays with a focus on correct overall statistics. The radioactive decay package presented in this work permits, for the first time, the use of both methods within the same simulation framework - Geant4. The accuracy of the statistical approach in our new package, RDM-extended, and that of the existing Geant4 per-decay implementation (original RDM), which has also been refactored, are verified against the ENSDF database. The new verified package is beneficial for a wide range of experimental scenarios, as it enables researchers to choose the most appropriate approach for their Geant4-based application.
THE RELATION OF THE SPLEEN TO BLOOD DESTRUCTION AND REGENERATION AND TO HEMOLYTIC JAUNDICE

After splenectomy anemia usually develops quickly and reaches its height in from three to six weeks; then with gradual improvement the blood picture approaches the normal after about three to four months, with complete return to normal in five to ten months. Accompanying this is marked leucocytosis reaching its height in twenty-four hours but persisting to a slight degree for several months. Variations, however, may occur, in that the anemia may develop slowly and be of slight degree, or the reparative process may be delayed and up to ten months incomplete. The anemia is, however, inevitable, as is also, later, some degree of repair.
A Randomised, Controlled Study of the Effects of Aerobic Exercise and Dietary Fish on Coagulation and Fibrinolytic Factors in Type 2 Diabetics

Summary Type 2 diabetes is associated with disturbances in coagulation and fibrinolysis. Prospective studies show that increased tissue plasminogen activator (tPA) antigen increases the risk of cardiovascular mortality. The present study examined the hypothesis that combining a regime of moderate aerobic exercise with one daily fish meal as part of a low-fat diet (30% total energy) would improve coagulation and fibrinolytic factors in dyslipidaemic type 2 diabetic patients. In a randomised, controlled, 8-week trial, 55 sedentary type 2 diabetic subjects with serum triglycerides >1.8 mmol/l and/or HDL-C <1.0 mmol/l were randomly assigned to a low-fat diet (30% daily energy intake) with or without one fish meal daily (3.6 g ω3 fatty acids/day) and further randomized to a moderate (55-65% VO2max) or light (heart rate <100 bpm) exercise program. Plasma levels of fibrinogen, coagulation factor VIIc, tPA and plasminogen activator inhibitor (PAI-1) antigen were measured before and after intervention. In the 49 subjects who completed the study, the fish diet alone, moderate exercise alone and the combination of fish and moderate exercise all led to significant reductions in tPA antigen concentrations (-2.1 ng/ml, p = 0.02, -1.9 ng/ml, p = 0.03, -2.0 ng/ml, p = 0.01, respectively) compared to controls. In multivariate regression, changes in fasting blood glucose (positively) and erythrocyte ω3 fatty acid composition (inversely) were independent predictors of the change in tPA antigen. The fish diet alone contributed to a significant rise in coagulation factor VIIc compared to controls (4.9%, p = 0.02), which was prevented by moderate exercise. No significant effects on PAI-1 antigen and fibrinogen were seen. In view of recent epidemiological findings, the reduction in tPA antigen with both fish and moderate exercise in these dyslipidaemic type 2 diabetic patients could reflect a reduced thrombotic potential and decreased cardiovascular risk. Furthermore, a small, albeit significant, increase in coagulation factor VIIc associated with fish can be prevented by a concomitant programme of moderate exercise.
Cognitive deficits as an endophenotype for anorexia nervosa: an accepted fact or a need for re-examination?

OBJECTIVE To investigate whether impaired set shifting and weak central coherence represent state or trait characteristics and, therefore, candidate endophenotypes of anorexia nervosa (AN). METHOD Forty-nine individuals with lifetime AN (24 acutely unwell, 10 weight recovered, and 15 fully recovered) and 43 healthy controls completed the Wisconsin Card Sorting Test (WCST), the Matching Familiar Figures Test, and the Rey Complex Figure Task measuring cognitive flexibility, local processing, and global processing, respectively. Participants also completed questionnaires assessing eating disorder, anxiety and depressive symptoms, obsessional traits, interpersonal functioning, and quality of life. Body mass index was calculated from height and weight measurements. RESULTS Participants with lifetime AN demonstrated poorer set shifting ability than healthy controls as evidenced by a greater number of perseverative errors on the WCST. When participants were grouped according to illness status, only those in the two recovered groups demonstrated poorer set shifting ability than healthy controls while patients with acute AN performed comparably to all other groups. There were no significant differences between groups on measures of local and global processing. No relationship was found between specific clinical features of AN and cognitive performance. DISCUSSION The results of this study are consistent with a global trend toward set shifting difficulties in patients with AN but do not support weak central coherence as a candidate endophenotype for AN. These findings have clinical implications in terms of treatment selection and planning, particularly in relation to the use of cognitive remediation therapy with patients with AN.
Assessment of the Influence of Citrate Concentration on the International Normalized Ratio (INR) Determined with Twelve Reagent-instrument Combinations

Summary Citrate concentration is one of the variables that can affect coagulation tests. However, few studies have so far been performed to assess the magnitude of this effect on coagulation tests in general and PT in particular. The aim of this study was to assess the extent of influence of citrate concentration on the PT test with results expressed as INR. Twelve reagent-instrument combinations (systems) were calibrated vs. the Reference Preparation BCT/441 using plasmas collected in either 105 mM or 129 mM citrate from normals and anticoagulated patients (OAT). PTs for plasmas collected in 129 mM citrate were longer than those collected in 105 mM both for normals and patients on OAT, but the ratios (patient-to-normal clotting times) for the two citrate concentrations were significantly different in many instances, implying that the International Sensitivity Index (ISI) is also different. ISIs for calibrations with plasmas collected in 105 mM were greater (up to 10%) than those with plasmas collected in 129 mM citrate. When PT ratios were transformed into INR using crossover ISIs (i.e., plasmas collected in 105 mM and ISI determined with plasmas collected in 129 mM citrate, or vice versa) we found that an INR of 4.5 could be up to 20% apart from the value that would have been obtained if the appropriate ISI was used. Moreover, if the ISI determined with the manual technique was used to convert PTs obtained with a particular instrument into INR, the effect of citrate concentration was even greater (INR difference up to 64%). Should these observations be valid for other systems, they might provide additional explanations for the frequent reports which document discrepancies in the INR determined with different systems to which incorrect ISI might have been applied. World-wide consensus on a single citrate concentration to collect patients’ as well as lyophilized plasmas to be used in External Quality Assessment Schemes and for local system calibration is therefore urgently needed.
Placental expression of arylamine N-acetyltransferases: evidence for linkage disequilibrium between NAT1*10 and NAT2*4 alleles of the two human arylamine N-acetyltransferase loci NAT1 and NAT2.

The study of placental xenobiotic metabolism is important for the determination of foetal exposure to environmental chemicals as placental metabolism influences the nature of chemicals reaching the foetus from its mother's blood. Arylamine N-acetyltransferases are drug metabolizing enzymes which N-acetylate hydrazines and arylamines, including carcinogenic arylamines and sulphonamide drugs. The two human arylamine N-acetyltransferase isoenzymes, NAT1 and NAT2, are encoded at multi-allelic loci. Here, we have determined N-acetyltransferase (NAT) activity in term placentas from normal, uncomplicated pregnancies. Both NAT1 and NAT2 enzyme activities were detectable. Placental NAT1 activity was at least 1000 fold greater than NAT2 activity. There was a 6 fold inter-placental variation in NAT1 activity. Mean placental NAT1 specific activity was 1.42 nmoles para-aminobenzoic acid N-acetylated.min-1.mg protein-1, which is comparable to NAT1 specific activities which have been measured in adult tissues. The NAT1, but not the NAT2, protein was detectable in placentas by Western blotting. Maternal and foetal NAT genotypes were determined from placenta, using placental blood clots and cord blood respectively, allowing NAT haplotype determination. There appeared to be linkage disequilbrium between NAT1* and NAT2* alleles such that the combination NAT1*10/NAT2*4 was found 3.5 times more frequently than would be expected.
Vocation and altruism in nursing

Background: At a time when British nursing has been under scrutiny for an apparent lack of compassion in education and practice, this paper based offers a perspective on the notions of vocation and altruism in nursing. Objectives: To understand the vocational and altruistic motivations of nurses through the application of Pierre Bourdieu's concepts of ‘symbolic capital’, ‘field’ and ‘habitus’ through a long interview with nurse respondents. Research design: A reflexive qualitative study was undertaken using the long interview. A thematic analysis of the data, using a qualitative data software package for analysis, was undertaken. The ideas of Pierre Bourdieu (Habitus, Capital and Field) were used to analyse and explain the content of community nurses' ‘talk’. Participants: Twelve Community Nurses working in a variety of local primary care settings volunteered to participate in the study. It was a self-selecting convenience sample of nurses responding to an invitation to be interviewed. Research context: A study in support of a doctoral thesis conducted within NHS primary care settings with registered nurses. Ethical considerations: The key considerations for this study were to be mindful of the possibility of emotional harm or distress being caused to the respondents during the retelling of their experiences. It was also essential to ensure that the locations or names of patients or staff (if discussed) were anonymised. Ethical approval was sought and granted by both the Local NHS Primary Care and the University Ethics committees before the study commenced. Findings: The nurse respondents had highly individual and at times contradictory views on their motivations to nurse including their views on vocation and altruism in nursing careers. Discussion: Bourdieu's ideas apply well to the nursing context and provided a useful theoretical framework to explore the social and cultural influences on nursing careers. Gender is important consideration in all aspects of nursing but class and educational experience is an important dimension in the stories nurses tell. Conclusion: The culturally determined experiences of these nurses in practice offer an authentic and realistic insight into the complex motives and predispositions of community nurses. This paper argues that nurse motivations whether vocational or altruistic, are better understood as culturally, rather than spiritually, driven.
Exploring the Relationship of Information Retrieval and Information Extraction

Information Retrieval (IR), Information Extraction (IE), and Text Classification (TC) are typically seen as related, but distinct fields. In IR the goal is to return documents relevant to a query, in IE the goal is to return strings representing insta ces of a particular class or relation, and in TC the goal is to determine to which class a test documen t b longs. While there are many techniques for each of IR, IE, and TC, we argue that for a r easonable and effective subset, the main distinction reduces to how the query and corpus are r epresented. We show how these subsets of IR, IE, and TC can be transformed to each other, and use these transformations to explore the implicit assumptions, limitations, and relati onship between example IR, IE, and TC systems. Finally, we use these insights to build a hybrid I E system, which uses IR distance metrics to improve the IE system’s results.
Carbapenem-resistant Acinetobacter baumannii (CRAB) Recovered from Burn Patients.

PURPOSE Emergence of carbapenem-resistant Acinetobacter baumannii (CRAB) and their prolonged presence in burn units increases the risk of acquisition of CRAB. Methods. From November 2012 to September 2013, 1474 burn patients were screened for CRAB isolates through testing susceptibility to imipenem and its comparators meropenem, and doripenem. Furthermore, the in vitro activity of other antibiotics against CRAB was investigated. Results. Three patients were infected with carbapenem-susceptible A. baumannii (CSAB) and 168 were infected with CRAB. Approximately one-fifth (n=32) of CRAB isolates were obtained from patients hospitalized in Burn Intensive Care Unit (BICU). Most of CRABs were isolated from wound. The mean length of stay (LOS) in hospital prior to A. baumannii isolation was significantly higher for CRAB compared to CSAB cases (P=0.04). Amongst the independent variables, percentage of total burn surface area (TBSA) significantly increased the mortality rate using multivariate logistic regression (P=0.001, OR= 16.5; 95% CI: 4.72-57.7). The majority of tested isolates were resistant to imipenem (94.8%), and to its comparators, doripenem (97.7%), and meropenem (97.7%). The susceptibility of CRAB isolates was less than 10% to all tested antibiotics except for colistin (100%), doxycycline (61.9%), gentamicin (18.5%), and tigecycline (11.9%). Conclusion. Resistance to carbapenem reduces the number of effective antibiotics. The coordinated and intensive efforts of healthcare personnel are required to meet the challenge of dissemination of CRAB.
Endothelial Gene Expression in Kidney Transplants with Alloantibody Indicates Antibody‐Mediated Damage Despite Lack of C4d Staining

Anti‐HLA alloantibody is a risk factor for graft loss, but does not indicate which kidneys are experiencing antibody‐mediated rejection (ABMR). C4d staining in biopsies is specific for ABMR but insensitive. We hypothesized that altered expression of endothelial genes due to alloantibody acting on the microcirculation would be sensitive indicator of ABMR. We identified 119 endothelial‐associated transcripts (ENDATs) from literature, and studied their expression by microarrays in 173 renal allograft biopsies for cause. Mean ENDAT expression was increased in all rejection but was higher in ABMR than in T‐cell‐mediated rejection and correlated with histopathologic lesions of ABMR, and alloantibody. Many individual ENDATs were increased in ABMR and predicted graft loss. Kidneys with high ENDATs and antibody showed increased lesions of ABMR and worse prognosis in comparison to controls. Only 40% of kidneys with high ENDAT expression and chronic ABMR or graft loss were diagnosed by C4d positivity. High ENDAT expression with antibody predicts graft loss with higher sensitivity (77% vs. 31%) and slightly lower specificity (71% vs. 94%) than C4d. The results were validated in independent set of 82 kidneys. High renal endothelial transcript expression in patients with alloantibody is indicator of active antibody‐mediated allograft damage and poor graft outcome.
The Monoclonal Antibody nBT062 Conjugated to Cytotoxic Maytansinoids Has Selective Cytotoxicity Against CD138-Positive Multiple Myeloma Cells In vitro and In vivo

Purpose: We investigated the antitumor effect of murine/human chimeric CD138-specific monoclonal antibody nBT062 conjugated with highly cytotoxic maytansinoid derivatives against multiple myeloma (MM) cells in vitro and in vivo. Experimental Design: We examined the growth inhibitory effect of BT062-SPDB-DM4, BT062-SMCC-DM1, and BT062-SPP-DM1 against MM cell lines and primary tumor cells from MM patients. We also examined in vivo activity of these agents in murine MM cell xenograft model of human and severe combined immunodeficient (SCID) mice bearing implant bone chips injected with human MM cells (SCID-hu model). Results: Anti-CD138 immunoconjugates significantly inhibited growth of MM cell lines and primary tumor cells from MM patients without cytotoxicity against peripheral blood mononuclear cells from healthy volunteers. In MM cells, they induced G2-M cell cycle arrest, followed by apoptosis associated with cleavage of caspase-3, caspase-8, caspase-9, and poly(ADP-ribose) polymerase. Nonconjugated nBT062 completely blocked cytotoxicity induced by nBT062-maytansinoid conjugate, confirming that specific binding is required for inducing cytotoxicity. Moreover, nBT062-maytansinoid conjugates blocked adhesion of MM cells to bone marrow stromal cells. The coculture of MM cells with bone marrow stromal cells protects against dexamethasone-induced death but had no effect on the cytotoxicity of immunoconjugates. Importantly, nBT062-SPDB-DM4 and nBT062-SPP-DM1 significantly inhibited MM tumor growth in vivo and prolonged host survival in both the xenograft mouse models of human MM and SCID-hu mouse model. Conclusion: These results provide the preclinical framework supporting evaluation of nBT062-maytansinoid derivatives in clinical trials to improve patient outcome in MM.