Miracle-dz/UniFAR-FTUs huggingface dataset:
Man1, an inner nuclear membrane protein, regulates vascular remodeling by modulating transforming growth factor β signaling

A growing number of integral inner nuclear membrane (INM) proteins have been implicated in diverse cellular functions. Man1, an INM protein, has recently been shown to regulate transforming growth factor (Tgf) β superfamily signaling by interacting with receptor-associated Smads. However, the in vivo roles of Man1 have not been fully characterized. Here, we show that Man1 regulates vascular remodeling by analyzing Man1-deficient embryos lacking the Smad interacting domain. Man1-deficient embryos die at midgestation because of defects in embryonic vasculature; the primary capillary plexus forms, but subsequent remodeling is perturbed. It has been proposed that the angiogenesis process is divided into two balanced phases, the activation and resolution/maturation phases, both of which are regulated by Tgfβ1. We have demonstrated, in Man1-deficient embryos, the expression of Tgfb1 is upregulated and Smad2/3 signaling is abnormally activated, resulting in increased extracellular matrix deposition, a hallmark of the resolution phase of angiogenesis. We have also showed that the recruitment of mural cells to the vascular wall is severely disturbed in mutants, which may lead to disruption of intercellular communication between endothelial and mural cells required for proper vascular remodeling. These results have revealed a novel role for Man1 in angiogenesis and provide the first evidence that vascular remodeling can be regulated at the INM through the interaction between Man1 and Smads.
Use of the plasma stromelysin (matrix metalloproteinase 3) concentration to predict joint space narrowing in knee osteoarthritis.

OBJECTIVE To determine whether baseline or serial plasma concentrations of stromelysin (matrix metalloproteinase 3 [MMP-3]) protein might distinguish subjects with progressive radiographic knee osteoarthritis (OA) from those with stable disease. METHODS Subjects were 120 women with unilateral knee OA who participated in a 30-month randomized, placebo-controlled trial of structure modification with doxycycline. Anteroposterior views of both knees in a semiflexed position were obtained at baseline, 16 months, and 30 months. Subjects were selected to obtain comparisons of plasma MMP-3 levels between 60 progressors (21 taking doxycycline, 39 taking placebo) and 60 nonprogressors (30 taking doxycycline, 30 taking placebo) with respect to medial joint space narrowing (JSN) in the index knee. Each group consisted of 30 subjects who exhibited significant increases in knee pain. Blood samples were obtained semiannually for MMP-3 assay. RESULTS Subjects in the placebo group whose MMP-3 concentration was in the upper tertile of the baseline distribution showed a 4-fold increase in the odds of progression of JSN as compared with the lower tertile (odds ratio 4.12, P = 0.037). Baseline MMP-3 levels were unrelated to knee pain. The within-subject mean of serial MMP-3 concentrations was associated with concurrent JSN in the placebo group over the 0-16-month interval (b = 0.18 mm/SD increase in the mean MMP-3, P < 0.01) and over the 16-30-month interval (b = 0.15, P < 0.05). Similar evidence of concurrent validity was found in the placebo group for the maximum of intercurrent MMP-3 values. CONCLUSION The baseline MMP-3 level was a significant predictor of JSN in this pilot study. Moreover, serial plasma MMP-3 levels reflected concurrent JSN in the placebo group over the 30-month period of observation.
Investigation of a nosocomial outbreak of severe acute respiratory syndrome (SARS) in Toronto, Canada.

BACKGROUND Severe acute respiratory syndrome (SARS) was introduced into Canada by a visitor to Hong Kong who returned to Toronto on Feb. 23, 2003. Transmission to a family member who was later admitted to a community hospital in Toronto led to a large nosocomial outbreak. In this report we summarize the preliminary results of the epidemiological investigation into the transmission of SARS between 128 cases associated with this hospital outbreak. METHODS We collected epidemiologic data on 128 probable and suspect cases of SARS associated with the hospital outbreak, including those who became infected in hospital and the next generation of illness arising among their contacts. Incubation periods were calculated based on cases with a single known exposure. Transmission chains from the index family to hospital contacts and within the hospital were mapped. Attack rates were calculated for nurses in 3 hospital wards where transmission occurred. RESULTS The cases ranged in age from 21 months to 86 years; 60.2% were female. Seventeen deaths were reported (case-fatality rate 13.3%). Of the identified cases, 36.7% were hospital staff. Other cases were household or social contacts of SARS cases (29.6%), hospital patients (14.1%), visitors (14.1%) or other health care workers (5.5%). Of the 128 cases, 120 (93.8%) had documented contact with a SARS case or with a ward where there was a known SARS case. The remaining 8 cases without documented exposure are believed to have had exposure to an unidentified case and remain under investigation. The attack rates among nurses who worked in the emergency department, intensive care unit and coronary care unit ranged from 10.3% to 60.0%. Based on 42 of the 128 cases with a single known contact with a SARS case, the mean incubation period was 5 days (range 2 to 10 days). INTERPRETATION Evidence to date suggests that SARS is a severe respiratory illness spread mainly by respiratory droplets. There has been no evidence of further transmission within the hospital after the elapse of 2 full incubation periods (20 days).
Heart Rate Elevation Precedes the Development of Metabolic Syndrome in Japanese Men: A Prospective Study

This observational study of Japanese men without metabolic syndrome (MetS) (age: 41±8 years) was conducted to clarify whether or not heart rate elevation precedes the development of full-blown MetS. MetS was defined based on two modifications of the criteria of the Japanese Expert Committee on the Diagnosis and Classification of Metabolic Syndrome. Premetabolic syndrome subjects were defined as those having one component of MetS with increased body mass index (BMI). Among the subjects without MetS (n=1,859 when the BMI criterion was ≥25 and n=2,020 when the BMI criterion was ≥27.5), the incidence of progression to full-blown MetS by the time of the second examination at the end of the 3-year study period was higher in the subjects with premetabolic syndrome than in those without it. The receiver-operator characteristic curve analysis and binary logistic regression analysis revealed that the odds ratio (OR) of a heart rate ≥69 beats/min at the first examination for progression to full-blown MetS by the time of the second examination was significant in subjects with premetabolic syndrome (BMI≥25: OR=3.64 [1.22–10.88]; BMI≥27.5: OR=3.67 [1.28–10.55]; p<0.05). Thus, heart rate elevation appears to precede the development of full-blown MetS in subjects with premetabolic syndrome. Heart rate seems to be a simple and useful marker for predicting the progression to full-blown MetS of middle-aged Japanese men with premetabolic syndrome.
Selective release of circRNAs in platelet-derived extracellular vesicles

ABSTRACT Circular RNAs (circRNAs) are a novel class of noncoding RNAs present in all eukaryotic cells investigated so far and generated by a special mode of alternative splicing of pre-mRNAs. Thereby, single exons, or multiple adjacent and spliced exons, are released in a circular form. CircRNAs are cell-type specifically expressed, are unusually stable, and can be found in various body fluids such as blood and saliva. Here we analysed circRNAs and the corresponding linear splice isoforms from human platelets, where circRNAs are particularly abundant, compared with other hematopoietic cell types. In addition, we isolated extracellular vesicles from purified and in vitro activated human platelets, using density-gradient centrifugation, followed by RNA-seq analysis for circRNA detection. We could demonstrate that circRNAs are packaged and released within both types of vesicles (microvesicles and exosomes) derived from platelets. Interestingly, we observed a selective release of circRNAs into the vesicles, suggesting a specific sorting mechanism. In sum, circRNAs represent yet another class of extracellular RNAs that circulate in the body and may be involved in signalling pathways. Since platelets are essential for central physiological processes such as haemostasis, wound healing, inflammation and cancer metastasis, these findings should greatly extend the potential of circRNAs as prognostic and diagnostic biomarkers.
Branching and laminar origin of projections between visual cortical areas in the cat

The laminar distribution and branching pattern of corticocortical neurons were studied in areas 17, 18, 19, 20, 21, and the lateral suprasylvian areas of the adult cat neocortex. This was done by examining the laminar position of single‐labelled neurons and the proportions of double‐labelled cells in these areas after paired injections of the fluorescent retrograde labels fast blue and diamidino yellow in areas 17, 18, and 19 of the ipsilateral hemisphere.
Mechanism controlling ovulation rate in ewes in relation to seasonal anoestrus.

Three experiments were carried out during seasonal anoestrus in Finnish Landrace and Scottish Blackface ewes, to establish whether the differences between the breeds in ovulation rate are functional during the non-breeding season and are therefore independent of the mechanism controlling ovulation. In Expt 1, follicles greater than or equal to 2 mm in diameter were dissected from the ovaries of both breeds and incubated individually for 2 h to assess their ability to secrete oestradiol and testosterone. In both breeds, follicles producing greater than or equal to 500 pg oestrogen/ml/h (oestrogen-active) were readily identifiable from a population producing less (oestrogen-inactive). The number of oestrogen-active follicles in each breed was similar to the number of ovulations near the end of the breeding season. Oestrogen-active follicles also had more luteinizing hormone (LH) receptors and larger diameters than oestrogen-inactive follicles. There were, however, no significant differences between the two follicle types in follicular fluid or in-vitro testosterone concentrations. In Expt 2, seasonally anoestrous Scottish Blackface ewes were unilaterally ovariectomized; the second ovary was removed 7 days later. Follicles from both ovaries were processed as described for Expt 1; oestrogen-active follicles were categorized according to their ability to produce greater than 500 pg/ml/h. There were twice as many oestrogen-active follicles in the second ovary as in the first ovary; the number of oestrogen-active follicles in the second ovary was also similar to the total number of oestrogen-active follicles in both ovaries of the Scottish Blackface ewes in Expt 1. (ABSTRACT TRUNCATED AT 250 WORDS)
Angiographic findings and catheterization laboratory events in patients with primary coronary angioplasty or streptokinase therapy for acute myocardial infarction.

BACKGROUND The purpose of this study was to evaluate catheterization laboratory events and angiographic findings in patients randomly assigned to undergo primary coronary angioplasty or to receive intravenous streptokinase for acute myocardial infarction. METHODS We analysed angiographic data in 301 patients with acute myocardial infarction, randomly assigned to undergo primary coronary angioplasty without antecedent thrombolytic therapy or to receive intravenous streptokinase therapy. Follow-up coronary angiography was preferably performed after 3 months. All angiograms were analysed with a quantitative coronary analysis system. RESULTS Of the 152 patients assigned to angioplasty treatment, 140 underwent this procedure with a success rate of 97%. The residual diameter stenosis of the infarct-related vessel immediately after angioplasty was 27 +/- 15% and there were major events in 14% of the patients in the catheterization laboratory. At follow-up angiography after a mean interval of 92 days in the angioplasty assigned patients, a diameter stenosis of 35 +/- 22% was observed in this group. The restenosis rate was 28% and the reocclusion rate 5%. A Thrombolysis in Myocardial Infarction (TIMI) grade 2 flow immediately after angioplasty was predictive for reocclusion at follow-up (P = 0.001). In the streptokinase assigned patients (149) the infarct-related vessel was patent at follow-up angiography after a mean of 22 days in 66% of the patients with a mean residual diameter stenosis of 77 +/- 20%. CONCLUSION Primary coronary angioplasty is a highly effective and safe reperfusion modality for patients with acute myocardial infarction. However, TIMI grade 2 flow through the infarct-related vessel immediately after angioplasty is a predictor of reocclusion.
Forward-premium puzzle: is it time to abandon the usual regression?

ABSTRACT The forward premium puzzle is usually evidenced by the rejection of the null hypothesis in the uncovered interest parity (UIP) regression. Because this parity need only hold in a risk-neutral world, a risk adjustment term is missing from the equation if speculation in foreign exchange markets is risky. We deal with this issue following the literature which assumes that discounted returns on foreign government bonds are log-normal, so we can linearize the Euler pricing equations (in level) and obtain a modified UIP system for which the risk adjustment term is obtained by applying to the pricing kernel-based relations a generalized autoregressive conditional heteroscedasticity-in-mean model. However, here we innovate by adopting a methodology which differs from all these related works. We construct and use a stochastic discount factor that does not depend on a specific model, by residing in the space of returns which we extract from the data by simply imposing the orthogonality restrictions represented by the Euler equations. So, we devise a purely statistical pricing kernel that performs well in in-sample level equations. Somewhat disappointingly, the risk premium inclusion in the conventional regression changes neither the significance nor the magnitude of the forecasting power of the forward premium for most currencies we study. The contrasting performance of the tests in level and in logs suggests that linearization may be to blame.
Role of investor sentiment in financial markets: an explanation by behavioural finance approach

The present paper has two objectives. The first is to analyse the correlation between investor sentiment and stock returns. The second is to explain the relationship between the financial market liquidity and the behaviour of its actors. From this perspective, we demonstrate that the investor sentiment is an important factor in generation of the stock performance based on the criterion of market capitalisation class shares, and then the investor sentiment is a combination of other indicators, including liquidity indicators of the financial market. Consequently, there exists a relationship between investor sentiment and stock returns. Thus, to verify this relationship, we studied a sample of 80 French industrial companies during a period of 58 months from January 2005 to October 2009. We have obtained the first result that investor sentiment is an explanatory variable only for small-caps returns. For the second result, we confirmed that the liquidity of the financial market deserves the role of sentiment measure. For the third result, we have proved that there is a significant correlation between investor sentiment and only the stock returns of small-cap. Finally, for the fourth result, we have validated the hypothesis showing that market liquidity can predict the psychological situation of investors.
PKR, a cognitive decline biomarker, can regulate translation via two consecutive molecular targets p53 and Redd1 in lymphocytes of AD patients

In Alzheimer’s disease (AD), the control of translation is dysregulated, precisely, two opposite pathways: double‐stranded RNA‐dependent protein kinase (PKR) is up‐regulated and mammalian target of rapamycin (mTOR) is down‐regulated. These biochemical alterations were found at the periphery in lymphocytes of AD patients and were significantly correlated with cognitive and memory test scores. However, the molecular crosslink between these two opposite signalling pathways remains unknown. The tumour suppressor p53 and Redd1 (regulated in development and DNA damage response) could be two downstream targets of active PKR to explain the breakdown of translation in AD patients. In this study, the protein and gene levels of p53 and Redd1 were assayed in lymphocytes of AD patients and in age‐matched controls by Western blotting and RT‐PCR. Furthermore, correlations were analysed with both the level of active PKR and the Mini Mental State Examination score (MMSE). The results show that the gene and protein levels of p53 and Redd1 were significantly increased about 1.5‐fold for both gene and Redd1 protein and 2.3‐fold for active p53 in AD lymphocytes compared to age‐matched controls. Furthermore, statistical correlations between proteins and genes suggest that active PKR could phosphorylate p53 which could induce the transcription of Redd1 gene. No correlations were found between MMSE scores and levels of p53 or Redd1, contrary to active PKR levels. PKR represents a cognitive decline biomarker able to dysregulate translation via two consecutive targets p53 and Redd1 in AD lymphocytes.
Oscillatory responses to reward processing in borderline personality disorder

Objectives. Previous electrophysiological studies have confirmed impaired reward processing in patients with BPD. However, it is not clear which aspects of reward processing are affected and which brain regions are involved. The present study investigated both evoked and induced event-related oscillations (EROs) to feedback events (thought to represent different aspects of feedback processing), and used source localization (sLORETA) to assess activity in two areas known to contribute to reward processing, the dorsomedial prefrontal/anterior cingulate cortex (dmPFC/ACC) and the orbitofrontal cortex (OFC). Methods. Eighteen patients with BPD and 22 healthy controls performed a gambling task, while 64-channel electroencephalographic activity was recorded. Evoked and induced theta and high-beta band EROs as well as activity in the two regions of interest were investigated depending on the valence and magnitude of feedback events. Results. Theta-band responses to negative feedback were reduced in BPD, an effect that involved only evoked responses and the dmPFC/ ACC region, and was associated with trait impulsivity in patients. sLORETA analyses revealed disturbed evoked responses depending on feedback magnitude in the theta (OFC) and high-beta (dmPFC/ACC and OFC) frequency range. Conclusions. The results indicate multiple dysfunctions of feedback processing in patients with BPD, implicating several distinct subsets of reward-processing mechanisms.
Characterizing and predicting coarse and fine particulates in classrooms located close to an urban roadway

The PM10, PM2.5, and PM1 (particulate matter with aerodynamic diameters <10, <2.5, and <1 μm, respectively) concentrations were monitored over a 90-day period in a naturally ventilated school building located at roadside in Chennai City. The 24-hr average PM10, PM2.5, and PM1 concentrations at indoor and outdoor environments were found to be 136 ± 60, 36 ± 15, and 20 ± 12 and 76 ± 42, 33 ± 16, and 23 ± 14 μg/m3, respectively. The size distribution of PM in the classroom indicated that coarse mode was dominant during working hours (08:00 a.m. to 04:00 p.m.), whereas fine mode was dominant during nonworking hours (04:00 p.m. to 08:00 a.m.). The increase in coarser particles coincided with occupant activities in the classrooms and finer particles were correlated with outdoor traffic. Analysis of indoor PM10, PM2.5, and PM1 concentrations monitored at another school, which is located at urban reserved forest area (background site) indicated 3–4 times lower PM10 concentration than the school located at roadside. Also, the indoor PM1 and PM2.5 concentrations were 1.3–1.5 times lower at background site. Further, a mass balance indoor air quality (IAQ) model was modified to predict the indoor PM concentration in the classroom. Results indicated good agreement between the predicted and measured indoor PM2.5 (R2 = 0.72–0.81) and PM1 (R2 = 0.81–0.87) concentrations. But, the measured and predicted PM10 concentrations showed poor correlation (R2 = 0.17–0.23), which may be because the IAQ model could not take into account the sudden increase in PM10 concentration (resuspension of large size particles) due to human activities. Implications: The present study discusses characteristics of the indoor coarse and fine PM concentrations of a naturally ventilated school building located close to an urban roadway and at a background site in Chennai City, India. The study results will be useful to engineers and policymakers to prepare strategies for improving the IAQ inside classrooms. Further, this study may help in the development of IAQ standards and guidelines in India.
Prevalence of HIV-1 in blood donations following implementation of a structured blood safety policy in South Africa.

CONTEXT The South African National Blood Service collects more than 700,000 units of blood annually from a population in which 11.4% is infected with human immunodeficiency virus 1 (HIV-1). The prevalence of HIV-1 in blood donations increased to 0.26% (1:385) in 1998, indicating that a significant number of window-period infective units were entering the blood supply (risk 3.4/100,000). OBJECTIVES To determine whether the implementation of a new donor selection policy and educational program introduced in 1999 was associated with reductions in the incidence and prevalence of HIV-1 in blood donations and the reduced transmission risk. DESIGN We compared the prevalence of HIV-1 in 880,534 blood donations collected from 1999 through 2000 with the 791,639 blood donations collected from 2001 through 2002. We estimated the incidence of HIV-1 in 93,378 (1999-2000) and 67,231 (2001-2002) first-time donations and the residual risk for all donations in 2001-2002 using the less-sensitive enzyme-linked immunoassay and incidence-window period model. SETTING All blood donors in the Inland region of the South African National Blood Service were analyzed. INTERVENTION Donor clinics in high HIV prevalence areas were closed. Programs targeting repeat donors and youth were initiated and HIV risk behavior education programs were developed. Structured donor interviews and an enhanced donor self-exclusion questionnaire were institutionalized. RESULTS The prevalence of HIV-1 in blood donations declined from 0.17% in 1999-2000 to 0.08% in 2001-2002 after the implementation of the new donor selection and education policy. The number of high-risk donations collected decreased from 2.6% to 1.7% (P<.001), and the likelihood of these donations being infected decreased from 4.8% to 3.25%. The likelihood of first-time donors being recently infected with HIV-1 decreased from 18% to 14% (P = .07) and respective incidence of high-risk donations collected decreased from 2.6% to 1.7%. Donations from the majority black population declined from 6.6% to 4.2% (P<.001). Analysis of HIV-1 incidence in 2001-2002 suggests a residual risk of collecting a window period infectious unit of 2.6/100,000. CONCLUSION The implementation of enhanced education and selection policies in South Africa was associated with decreased prevalence of HIV-1 in blood donations.