Miracle-dz/UniFAR-FTUs huggingface dataset:
Can Biomarkers Identify Women at Increased Stroke Risk? The Women's Health Initiative Hormone Trials

Objective: The Women's Health Initiative hormone trials identified a 44% increase in ischemic stroke risk with combination estrogen plus progestin and a 39% increase with estrogen alone. We undertook a case-control biomarker study to elucidate underlying mechanisms, and to potentially identify women who would be at lower or higher risk for stroke with postmenopausal hormone therapy (HT). Design: The hormone trials were randomized, double-blind, and placebo controlled. Setting: The Women's Health Initiative trials were conducted at 40 clinical centers in the United States. Participants: The trials enrolled 27,347 postmenopausal women, aged 50–79 y. Interventions: We randomized 16,608 women with intact uterus to conjugated estrogens 0.625 mg with medroxyprogesterone acetate 2.5 mg daily or placebo, and 10,739 women with prior hysterectomy to conjugated estrogens 0.625 mg daily or placebo. Outcome Measures: Stroke was ascertained during 5.6 y of follow-up in the estrogen plus progestin trial and 6.8 y of follow-up in the estrogen alone trial. Results: No baseline clinical characteristics, including gene polymorphisms, identified women for whom the stroke risk from HT was higher. Paradoxically, women with higher baseline levels of some stroke-associated biomarkers had a lower risk of stroke when assigned to estrogen plus progestin compared to placebo. For example, those with higher IL-6 were not at increased stroke risk when assigned to estrogen plus progestin (odds ratio 1.28) but were when assigned to placebo (odds ratio 3.47; p for difference = 0.02). Similar findings occurred for high baseline PAP, leukocyte count, and D-dimer. However, only an interaction of D-dimer during follow-up interaction with HT and stroke was marginally significant (p = 0.03). Conclusions: Biomarkers did not identify women at higher stroke risk with postmenopausal HT. Some biomarkers appeared to identify women at lower stroke risk with estrogen plus progestin, but these findings may be due to chance.
Discrimination of Virtual Square Gratings by Dynamic Touch on Friction Based Tactile Displays

In this paper, we investigate the use of friction based tactile displays for the simulation of finely textured surfaces, as such displays offer a promising way for the development of devices with co-located vision and tactile feedback. The resolution of the textures rendered with such devices and their matching to real textures have never been investigated. The paper first contributes to the evaluation of the texture resolution of friction based tactile displays. In a controlled experiment, we investigate the differential thresholds for square gratings simulated with a friction based tactile device by dynamic touch. Then we compare them to the differential thresholds of real square wave gratings. We found that the Weber fraction remains constant across the different spatial period at 9%, which is close to the Weber fraction found for corresponding real square gratings. This study inclines us to conclude that friction based tactile displays offers a realistic alternative to pin based arrays and can be used for co-located vision and tactile rendering. From the results of the experiment, we also give the design guidelines to improve the perception of textures on friction based tactile displays.
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: structural MR imaging changes and apolipoprotein E genotype.

BACKGROUND AND PURPOSE Apolipoprotein E (apoE) genotype plays an important role in the development, maintenance, and response to injury of the central nervous system. It has been suggested that apoE epsilon4 genotype is a risk factor for several neurologic disorders. We investigated the correlation between the apoE genotype and radiologic data in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). METHODS T1-weighted, dual fast spin-echo, T2*-weighted gradient echo, and fluid-attenuated inversion recovery MR imaging scans were obtained from 36 CADASIL patients (21-59 years of age). The number of lacunar infarcts and microbleeds and the presence of subcortical lacunar lesions were determined. The amount of white matter hyperintensities was assessed by using semiautomated segmentation software. The relation between the radiologic endophenotype of CADASIL and the apoE genotype was assessed by using a Student t test for unpaired data and Fisher exact test. RESULTS White matter hyperintensities, lacunar infarcts, microbleeds, and subcortical lacunar lesions were not found to be associated with the presence of an epsilon4 allele. CONCLUSION The variability of structural MR imaging lesions in CADASIL is independent of apoE genotype and other processes must underlie the variable natural history of the disease.
Estimating CO2 exchange at two sites in Arctic tundra ecosystems during the growing season using a spectral vegetation index

Measurements of carbon fluxes in Arctic tundra landscapes are generally obtained through intensive field work and involve the use of chamber and/or micrometeorological tower techniques. However, findings in a variety of nonArctic ecosystems have demonstrated the potential of remote sensing-based techniques (particularly spectral vegetation indices) to provide estimates of CO2 exchange in a more timely and efficient manner. As the firststep towards modelling Arctic regional and circumpolar fluxes of CO2 using remotely sensed data, we investigated the relationships between plot-level fluxes of CO2 and a vegetation spectral reflectance index derived from hand-held radiometric data at two sites. These relationships were evaluated for variations in vegetation cover type and environmental factors using data collected during the short Arctic growing season. Overall, this study demonstrated a relationship between the Normalized Difference Vegetation Index (NDVI) and measurements of mean site gross photosynthesis .
Involvement of chromatin and histone deacetylation in SV40 T antigen transcription regulation

Simian Virus 40 (SV40) large T antigen (T Ag) is a multifunctional viral oncoprotein that regulates viral and cellular transcriptional activity. However, the mechanisms by which such regulation occurs remain unclear. Here we show that T antigen represses CBP-mediated transcriptional activity. This repression is concomitant with histone H3 deacetylation and is TSA sensitive. Moreover, our results demonstrate that T antigen interacts with HDAC1 in vitro in an Rb-independent manner. In addition, the overexpression of HDAC1 cooperates with T antigen to antagonize CBP transactivation function and correlates with chromatin deacetylation of the TK promoter. Finally, decreasing HDAC1 levels with small interfering RNA (siRNA) partially abolishes T antigen-induced repression. These findings highlight the importance of the histone acetylation/deacetylation balance in the cellular transformation mediated by oncoviral proteins.
The earth is flat (p > 0.05): significance thresholds and the crisis of unreplicable research

The widespread use of ‘statistical significance’ as a license for making a claim of a scientific finding leads to considerable distortion of the scientific process (according to the American Statistical Association). We review why degrading p-values into ‘significant’ and ‘nonsignificant’ contributes to making studies irreproducible, or to making them seem irreproducible. A major problem is that we tend to take small p-values at face value, but mistrust results with larger p-values. In either case, p-values tell little about reliability of research, because they are hardly replicable even if an alternative hypothesis is true. Also significance (p ≤ 0.05) is hardly replicable: at a good statistical power of 80%, two studies will be ‘conflicting’, meaning that one is significant and the other is not, in one third of the cases if there is a true effect. A replication can therefore not be interpreted as having failed only because it is nonsignificant. Many apparent replication failures may thus reflect faulty judgment based on significance thresholds rather than a crisis of unreplicable research. Reliable conclusions on replicability and practical importance of a finding can only be drawn using cumulative evidence from multiple independent studies. However, applying significance thresholds makes cumulative knowledge unreliable. One reason is that with anything but ideal statistical power, significant effect sizes will be biased upwards. Interpreting inflated significant results while ignoring nonsignificant results will thus lead to wrong conclusions. But current incentives to hunt for significance lead to selective reporting and to publication bias against nonsignificant findings. Data dredging, p-hacking, and publication bias should be addressed by removing fixed significance thresholds. Consistent with the recommendations of the late Ronald Fisher, p-values should be interpreted as graded measures of the strength of evidence against the null hypothesis. Also larger p-values offer some evidence against the null hypothesis, and they cannot be interpreted as supporting the null hypothesis, falsely concluding that ‘there is no effect’. Information on possible true effect sizes that are compatible with the data must be obtained from the point estimate, e.g., from a sample average, and from the interval estimate, such as a confidence interval. We review how confusion about interpretation of larger p-values can be traced back to historical disputes among the founders of modern statistics. We further discuss potential arguments against removing significance thresholds, for example that decision rules should rather be more stringent, that sample sizes could decrease, or that p-values should better be completely abandoned. We conclude that whatever method of statistical inference we use, dichotomous threshold thinking must give way to non-automated informed judgment.
Basolateral Entry and Release of New and Old World Arenaviruses from Human Airway Epithelia

ABSTRACT Transmission of arenaviruses from rodent hosts to humans is generally thought to occur through inhalation or ingestion of dust or droplets containing viral particles. Here we demonstrate that two identified arenavirus receptors, α-dystroglycan (α-DG) and transferrin receptor 1 (TfR1), are expressed in polarized human airway epithelia. Lymphocytic choriomeningitis virus strains with high or low α-DG affinity and Junin virus, which binds TfR1, efficiently infected polarized epithelia only when applied to the basolateral surface or when injury compromised tight junction integrity. Viral egress from infected epithelia exhibited basolateral polarity. This study demonstrates that respiratory entry of arenaviruses occurs via basolateral receptors.
On the soundness of authenticate-then-encrypt: formalizing the malleability of symmetric encryption

A communication channel from an honest sender A to an honest receiver B can be described as a system with three interfaces labeled A, B, and E (the adversary), respectively, where the security properties of the channel are characterized by the capabilities provided at the E-interface. A security mechanism, such as encryption or a message authentication code (MAC), can be seen as the transformation of a certain type of channel into a stronger type of channel, where the term "transformation" refers to a natural simulation-based definition. For example, the main purpose of a MAC can be regarded as transforming an insecure into an authenticated channel, and encryption then corresponds to transforming an authenticated into a fully secure channel; this is the well-known Encrypt-then-Authenticate (EtA) paradigm. In the dual paradigm, Authenticate-then-Encrypt (AtE), encryption first transforms an insecure into a confidential channel, and a MAC transforms this into a secure channel. As pointed out by Bellare and Namprempre, and Krawczyk, there are encryption schemes for which AtE does not achieve the expected guarantees. We highlight two reasons for investigating nevertheless AtE as a general paradigm: First, this calls for a definition of confidentiality; what separates a confidential from a secure channel is its (potential) malleability. We propose the first systematic analysis of malleability for symmetric encryption, which, in particular, allows us to state a generic condition on encryption schemes to be sufficient for AtE. Second, AtE is used in practice, for example in TLS. We show that the schemes used in TLS (stream ciphers and CBC encryption) satisfy the condition. This is consistent with Krawczyk's results on similar instantiations of AtE in game-based models.
The degree of acute descending control of spinal nociception in an area of primary hyperalgesia is dependent on the peripheral domain of afferent input

Acute inflammation engages various descending control systems in the brain that alter the resulting inflammatory pain, usually by inhibiting it. In this study we looked at the differences in inhibition of acute (up to 3 h) inflammatory pain from smooth (glabrous) and hairy skin in the rat hind foot. In hairy skin, inflammatory pain is rapidly inhibited by descending systems that release noradrenaline, but not opiates, into the spinal cord. In glabrous skin, neither descending noradrenergic nor opioidergic controls affect inflammatory pain. These results tell us that the controls on the spinal processing of cutaneous inflammatory pain differ according to the skin type affected.
Estructura y función de pastizales mediterráneos

SE ESTUDIA LA ESTRUCTURA Y FUNCION DE PASTIZALES CONSIDERADOS COMO ECOSISTEMAS: ESTE ES EL NIVEL DE ORGANIZACION OBJETO DE INVESTIGACION. PARA COMPRENDER EL ALCANCE TEORICO ECOLOGICO DE LA MISMA, ES ESENCIAL RECONOCER ESTA CUALIDAD DISTINTIVA DE LA APROXIMACION UTILIZADA. LOS PASTIZALES ESTUDIADOS SE HALLAN EN EL CENTRO DE LA PENINSULA IBERICA, EN EL SECTOR ORIENTAL DEL SISTEMA CENTRAL Y SU PEDIMENTO, UN AREA DE SUSTRATO SILICEO. SON MEDITERRANEOS PORQUE ASI SE DENOMINA AL REGIMEN CLIMATICO CARACTERISTICO DE LA REGION GEOGRAFICA DONDE SE LOCALIZAN. SE HAN CONSIDERADO SIETE LOCALIDADES SITUADAS A LO LARGO DE UN GRADIENTE ALTITUDINAL ENTRE 500 Y 1800 M. ESTA REPRESENTA LA PRINCIPAL FUENTE DE VARIACION AMBIENTAL, QUE DETERMINA UN CAMBIO MESOCLIMATICO GRADUAL: CON LA ALTITUD AUMENTA LA HUMEDAD Y DISMINUYE LA TEMPERATURA. ADEMAS SE HA CONSIDERADO UNA FUENTE DE VARIACION LOCAL DE TIPO GEOMORFOLOGICO, DEFINIDA POR DOS ZONAS DE LADERA DIFERENTES. EN SEIS LOCALIDADES SE HAN REALIZADO TRES TIPOS DIFERENTES DE PERTURBACIONES EXPERIMENTALES CUYOS EFECTOS SE HAN OBSERVADO A LO LARGO DE UN PERIODO DE CINCO ANOS. EN TODOS LOS CASOS EL CONTRASTE EFECTUADO HA INCLUIDO LA COMPARACION CON UN CONTROL. LAS PERTURBACIONES UTILIZADAS SON: ROTURACION, CERCADO Y UNA COMBINACION DE AMBAS. CONSTITUYEN FACTORES EXTERNOS AL ECOSISTEMA CUYO USO PERMITE INVESTIGAR EXPERIMENTALMENTE LA ESTRUCTURA Y EL FUNCIONAMIENTO DE LOS PASTIZALES. SE DESCRIBE DE FORMA SUMARIA LA VARIACION MESOCLIMATICA Y DE LAS CARACTERISTICAS FISICAS Y QUIMICAS DE LOS SUELOS. LAS DIFERENCIAS DEL REGIMEN CLIMATICO Y BALANCE HIDRICO DE DOS LOCALIDADES DE ALTITUD MUY CONTRASTADA SE ANALIZAN CON CIERTO DETALLE. LA INTEGRACION DE LAS CARACTERISTICAS EDAFICAS Y CLIMATICAS PERMITE EVALUAR DE FORMA CUANTITATIVA SUS DIFERENCIAS EN LA DURACION E INTENSIDAD DEL DEFICIT HIDRICO CARACTERISTICO DEL CLIMA MEDITERRANEO: CON LA ALTITUD EL CLIMA SE HACE MENOS ESTACIONAL. SON DIVERSAS LAS CARACTERISTI
Major Depletion of Plasmacytoid Dendritic Cells in HIV-2 Infection, an Attenuated Form of HIV Disease

Plasmacytoid dendritic cells (pDC) provide an important link between innate and acquired immunity, mediating their action mainly through IFN-α production. pDC suppress HIV-1 replication, but there is increasing evidence suggesting they may also contribute to the increased levels of cell apoptosis and pan-immune activation associated with disease progression. Although having the same clinical spectrum, HIV-2 infection is characterized by a strikingly lower viremia and a much slower rate of CD4 decline and AIDS progression than HIV-1, irrespective of disease stage. We report here a similar marked reduction in circulating pDC levels in untreated HIV-1 and HIV-2 infections in association with CD4 depletion and T cell activation, in spite of the undetectable viremia found in the majority of HIV-2 patients. Moreover, the same overexpression of CD86 and PD-L1 on circulating pDC was found in both infections irrespective of disease stage or viremia status. Our observation that pDC depletion occurs in HIV-2 infected patients with undetectable viremia indicates that mechanisms other than direct viral infection determine the pDC depletion during persistent infections. However, viremia was associated with an impairment of IFN-α production on a per pDC basis upon TLR9 stimulation. These data support the possibility that diminished function in vitro may relate to prior activation by HIV virions in vivo, in agreement with our finding of higher expression levels of the IFN-α inducible gene, MxA, in HIV-1 than in HIV-2 individuals. Importantly, serum IFN-α levels were not elevated in HIV-2 infected individuals. In conclusion, our data in this unique natural model of “attenuated” HIV immunodeficiency contribute to the understanding of pDC biology in HIV/AIDS pathogenesis, showing that in the absence of detectable viremia a major depletion of circulating pDC in association with a relatively preserved IFN-α production does occur.
Foreword: SEDES 2012 - Fourth Portuguese Software Engineering Doctoral Symposium

The Fourth edition of the Portuguese Software Engineering Doctoral Symposium (SEDES 2012) was held on 3 September 2012 in Lisbon, colocated with the QUATIC 2012 conference. The aim of this symposium is to bring together software engineering PhD students supervised or co-supervised by faculty members of Portuguese universities in a constructive environment where they can present and discuss their ongoing PhD projects. The symposium aims at selecting PhD students that have already settled on a specific research topic, but are at least one year apart from delivering their dissertation, so that they can still benefit from the symposium discussions. This symposium is also instrumental as a gathering point for the Software Engineering researchers in Portugal, with a tradition of synergies facilitator since its first edition. As such, an effort has been made to hold this event in different towns. The eligible topics for participation in SEDES include all knowledge areas defined in SWEBOK. Research work in related fields such as Computer Science (including formal methods) and Information Systems (including Information Services variants) are considered within the scope of SEDES if they hold an applied perspective on the technological or methodological issues of software development or maintenance.
Psychometric Evaluation of the Glaucoma Symptom Identifier

ObjectiveTo evaluate the psychometric properties of the Glaucoma Symptom Identifier (GSI), a tool designed to assess multiple possible glaucoma symptoms and their impact on quality of life in clinical practice. We sought to address the need for better methods to assess visual function related to quality of life of glaucoma patients with a tool to show to both physicians and their patients that glaucoma is not an asymptomatic disease. The development process was to provide comprehensive assessment in 1 page of the impact of glaucoma on patients' quality of life by including an exhaustive list of unique and nonredundant items. DesignCross-sectional online survey. ParticipantsSeven hundred and eighteen individuals with a self-reported diagnosis of glaucoma, who were at least 40 years of age. MethodsThe impact of glaucoma was assessed by asking study participants the degree of difficulty they experience on a number of tasks. Item response theory was used to psychometrically evaluate the GSI. Scores on the GSI and the SF-12, a generic quality-of-life instrument, were compared. Main Outcome MeasuresItems in the GSI were categorized in terms of their ability to capture glaucoma impact on quality of life across the population range of subjects from mild–to-severe glaucoma severity. ResultsThe GSI showed good reliability, and convergent and discriminant validity. Items in the GSI captured glaucoma impact on quality of life over an adequate range of disease severity. Potential improvements to the existing questionnaire were identified using item response theory modeling results and respondents' feedback on the survey. ConclusionsOur findings suggest that the GSI is a psychometrically valid tool, adequate for glaucoma patients' self-administration within a clinician's routine practice to help both the patient and physician assess the patient's current and potential future symptoms of glaucoma.
Value of 18F-FDG PET/CT for Early Prediction of Pathologic Response (by Residual Cancer Burden Criteria) of Locally Advanced Breast Cancer to Neoadjuvant Chemotherapy

Purpose A relatively new pathologic grading system, called residual cancer burden (RCB) criteria (0 to III), for assessing the response to neoadjuvant chemotherapy (NCT) of breast cancer has been reported to be more accurate than conventional pathologic criteria. This study assesses the value of 18F-FDG PET/CT in early prediction of chemotherapeutic response determined based on these criteria. Patients and Methods Thirty-six patients with locally advanced breast cancer underwent 18F-FDG PET/CT before and after the first (just before the second) cycle of NCT. Percentage changes (%△) in SUVmax, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) between 18F-FDG PET/CT before and after the first cycle of NCT were correlated with RCB index on pathologic specimens after the completion of NCT. Results The %△SUVmax, %△MTV, and %△TLG in the RCB 0/I group (n = 5) were all significantly larger than those in the RCB II/III group (n = 31) (82.9%, 100%, and 100% vs 45.8%, 83.2%, and 88.0%, respectively, P < 0.01). The sensitivity/specificity/accuracy of the optimal cutoff %△SUVmax, %△MTV, and %△TLG for discriminating RCB 0/I group from RCB II/III group based on the receiver operating characteristic analysis were 80.0%/96.8%/94.4%, 100%/80.6%/83.3%, and 100%/80.6%/83.3%, respectively. The area under the curve for the 3 parameters was 0.923, 0.903, and 0.884, respectively, and not statistically different. Conclusions The %&Dgr;metabolic parameters derived from 18F-FDG PET/CT studies performed before and after the first cycle of NCT in patients with locally advanced breast cancer appear to be useful in early prediction of eventual therapy response determined based on the RCB pathologic grading system.