Miracle-dz/UniFAR-FTUs huggingface dataset:
Prediction of the warfarin maintenance dose after completion of the 10 mg initiation nomogram: do we really need genotyping?

Summary. Introduction: Initiation of warfarin therapy is complicated by its narrow therapeutic index and inter‐patient dose‐effect variability. A ‘10‐mg nomogram’ warfarin initiation protocol permits safe therapeutic anticoagulation in outpatients started on warfarin. We aimed to develop a safe and effective warfarin maintenance dose prediction tool in these patients. Methods: Baseline potential predictor variables were collected on a retrospective cohort of outpatients initiated on warfarin for venous thromboembolism treatment. The primary outcome was the warfarin maintenance dose, defined as mean warfarin dose over the last 10 days of the first month of warfarin treatment. Univariate and multivariate analyses were performed to determine which baseline variables were warfarin maintenance dose predictors. An independent cohort of patients validated the derived warfarin maintenance dose prediction rule. Results: Patient’s age and weight, cumulative dose of warfarin over the first week of induction and international normalized ratio (INR) on days 3, 5 and 8 were statistically significant predictors of the warfarin maintenance dose. Our final prediction rule reads: maintenance dose (in mg) = 2.5 + 10% of the first week cumulative dose ‐ INR value at day 8 + 1.5 if INR was below 2.0 at day 5. In the validation cohort, the predicted dose was strongly correlated with the actual maintenance dose (r = 0.88, P < 0.0001). The mean difference between observed and predicted dose was not clinically significant: −0.1 ± 1.1 mg. Conclusion: In outpatients initiated on warfarin using a ‘10‐mg nomogram’, a simple prediction rule can accurately predict warfarin maintenance dose. Prospective studies employing the rule are indicated.
A comparison of the T cell delayed‐type hypersensitivity epitopes of the 19‐kD antigens from Mycobacterium tuberculosis and Myco. intracellulare using overlapping synthetic peptides

Mycobacterial disease remains a serious international public health concern. Improved methods to rapidly and specifically detect mycobacterial infections would greatly enhance clinical management of these diseases. To define species‐specific T cell epitopes that may be useful for the immunodiagnosis of mycobacterial infections, polymerized synthetic peptides from the 19‐kD Mycobacterium tuberculosis and Myco. intracellulare protein homologues were tested in guinea pig DTH assays. Five Myco. tuberculosis and eight Myco. intracellulare peptides evoked skin test responses. Although all of the active Myco. tuberculosis and seven of the Myco. intracellulare peptides elicited non‐specific DTH reactions, the peptide IN13 induced a Myco intracellulare‐specific skin test reaction, and thus represents a specific Myco intracellulare T cell DTH epitope. This result suggests that the development of monospecific peptide‐based immunodiagnostic reagents may be feasible for future clinical use.
Estimating Reference Evapotranspiration using Data Mining Prediction Models and Feature Selection

Since the irrigated agriculture is the most water-consuming sector in Brazil, it is a challenge to use water in a sustainable way. Evapotranspiration is the combination process of transferring moisture from the earth to the atmosphere by evaporation and transpiration from plants. By estimating this rate of loss, farmers can efficiently manage the crop water requirement and how much water is available. In this work, we propose prediction models, which can estimate the evapotranspiration based on climatic data collected by an automatic meteorological station. Climatic data are multidimensional, therefore by reducing the data dimensionality, then irrelevant, redundant or non-significant data can be removed from the results. In this way, we consider in the proposed solution to apply feature selection techniques before generating the prediction model. Thus, we can estimate the reference evapotranspiration according to the collected climatic variables. The experiments results concluded that models with high accuracy can be generated by M5’ algorithm with feature selection techniques.
Response: HIV-1 Evolution and Disease Progression

REFERENCES AND NOTES se that destroys the host. Thus, within a particular host, diversity is driven by the collective sum of all the selective forces acting on the HIV-1 quasispecies virus population, rather than a specific immune parameter by or in itself (4). The theory predicts two possible outcomes. First, infected individuals with diversity higher than their individual specific threshold lose immune control and rapidly progress to AIDS, while those below their individual specific threshold remain clinically stable. Second, an increase in antigenic diversity over time in the same individual gives rise to loss of immune control and faster progression to AIDS once the individual's specific threshold is crossed. The fact that the magnitude of the diversity threshold could be different in different infected individuals is a result of the inherent plasticity of the mathematical model used to derive the antigenic diversity threshold theory (1, 2). As a consequence, the model becomes virtually untestable. The actual model could encompass many different possible parameters that can trigger the trajectory to AIDS, all of which are sensitive to initial conditions (5) and better expressed as a nondimensional threshold condition (6). Thus, stochastic simulations of the infection process only partially characterize the model dynamics (5). The results of our study (7) do not support a model that relates increasing antigenic diversity to pathogenic progres-
Deregulation of MiR-34b/Sox2 Predicts Prostate Cancer Progression

Most men diagnosed with prostate cancer will have an indolent and curable disease, whereas approximately 15% of these patients will rapidly progress to a castrate-resistant and metastatic stage with high morbidity and mortality. Therefore, the identification of molecular signature(s) that detect men at risk of progressing disease remains a pressing and still unmet need for these patients. Here, we used an integrated discovery platform combining prostate cancer cell lines, a Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model and clinically-annotated human tissue samples to identify loss of expression of microRNA-34b as consistently associated with prostate cancer relapse. Mechanistically, this was associated with epigenetics silencing of the MIR34B/C locus and increased DNA copy number loss, selectively in androgen-dependent prostate cancer. In turn, loss of miR-34b resulted in downstream deregulation and overexpression of the “stemness” marker, Sox2. These findings identify loss of miR-34b as a robust biomarker for prostate cancer progression in androgen-sensitive tumors, and anticipate a potential role of progenitor/stem cell signaling in this stage of disease.
Organization of neurons in the visual cortex, area 17, of the monkey (Macaca mulatta)

A study of neuron morphology in Golgi Rapid and Kopsch preparations of area 17 of the monkey has shown three basic cell groups— pyramidal neurons, stellate neurons with spinous dendrites and stellate neurons with spine‐free or sparsely spined dendrites. These three neuron groups show different distributions in depth from pia to white matter and differ in their relationship to zones of concentrated termination of geniculo‐cortical axons. The neuron type most closely related to the laminae receiving a heavy geniculo‐cortical projection is the spinous stellate cell. This cell type is restricted to lamina IV. Included in this zone is the broadest band of geniculo‐cortical axon projection (lamina IVC), the horizontal fiber band (lamina IVB) comprising the major portion of the stria of Gennari (receiving little or no thalamic projection) and the narrow band of thalamo‐cortical fiber termination which occurs superficial to the stria of Gennari (lamina IVA). Pyramidal neuron cell bodies are almost totally excluded from lamina IVC and the apical dendrites of lower pyramidal neurons bear many fewer spines in lamina IVC than in laminae V and VI. The basal dendrites of upper pyramidal cells spread superficial and deep to lamina IVA rather than within it. Spine‐free stellate neurons occur at all cortical levels and sparselyspined varieties have not been impregnated in lamina IV, but occur in the other laminae.
Die Rückgewinnung von Feuchtgebieten als eine Lösung für aktuelle Umweltprobleme : Hemmnisse und Möglichkeiten

Feuchtgebiete sind Okosysteme, die durch die Anwesenheit von Wasser, spezielle Bodenverhaltnisse und eine besondere Vegetationszusammensetzung gepragt sind. Sie zahlen zu den am starksten bedrohten Okosystemen der Erde. Im Verlauf des 20. Jahrhunderts nahm weltweit sowohl ihre Flache als auch ihre Qualitat (bezuglich Artenvielfalt etc.) stark ab. Viele von Wasser beeinflusste Flachen, v.a. in Flussauen, wurden gezielt entwassert, um sie fur Siedlungen, Industrie oder wegen der fruchtbaren Boden fur intensive Landwirtschaft nutzbar zu machen. Im naturlichen Zustand stellen Flachen mit Feuchtgebieten allerdings ebenfalls wertvolle okonomische Ressourcen dar (u.a. dienen sie dem Hochwasserschutz, der Nahrstoffspeicherung, Erholung und Naturschutz), so dass eine Umwandlung bzw. Degradation dieses Naturkapitals oft nicht zu einer wirklichen Steigerung der gesellschaftlichen Wohlfahrt fuhrt. Im Rahmen der Betrachtung der Problematik der Erhaltung und der Ruckgewinnung von Uberschwemmungsflachen, welche im Fokus dieser Arbeit stehen, werden Flachennutzungskonflikte in Flussgebieten in Verbindung mit den Schwierigkeiten des institutionellen Rahmens deutscher Bodenmarkte untersucht. Zur Scharfung der Argumentation wird ein extremes Beispiel fur die Ruckgewinnung von Feuchtgebieten - der Abbruch einer Siedlung im potenziellen Uberschwemmungsbereich eines Flusses - herausgegriffen. Eine abstrakte Einheitssiedlung sowie tatsachliche Umsiedlungen dienen der Ermittlung der volkswirtschaftlichen Kosten eines solchen Vorhabens, welche dann den in anderen Studien erfassten Nutzen von Feuchtgebieten gegenubergestellt werden konnen. Die Berechnungen zeigen, dass es schon allein unter Berucksichtigung der zum Schutz der Siedlung notwendigen Erhaltungs- und Erneuerungskosten eines Hochwasserschutzdeiches ab einem bestimmten Zeitpunkt empfehlenswert sein kann, diese Siedlung nicht weiter aufrecht zu erhalten. Der Nutzen des zu erstellenden Feuchtgebietes muss hier gar nicht bekannt sein, um eine Entscheidung zugunsten einer Absiedlung zu treffen (allerdings: starke Sensitivitat gegenuber den verwendeten Diskontsatzen). Daneben kann gezeigt werden, dass ein optimaler Zeitpunkt fur Abbruch bzw. Umsiedlung ermittelt werden kann, bei welchem die Differenz zwischen Nutzen und Kosten des Vorhabens maximal ist.
A Q Method Approach to Evaluating Farmers’ Perceptions of Foot-and-Mouth Disease Vaccination in Vietnam

This study aims to explore the farmers’ perceptions of foot-and-mouth disease (FMD) vaccination using a reflexive research method called Q methodology. A structured sample was composed of 46 farmers selected according to gender, farming experience, level of education, and production type. Statements relevant to the farmers’ perceptions of and attitudes toward FMD vaccination, related to confidence, logistics, costs, and impacts of vaccination were developed. Results were analyzed by principal component analysis and factor analysis. The influence of demographics and characterized variables on the respondent’s contribution to each factor was also tested. Regarding the different beliefs and behavior toward FMD vaccination, the common perceptions held by Vietnamese cattle and pig farmers were divided into three discourses named Confidence (24 subjects), Belief (12 subjects), and Challenge (6 subjects). The identified discourses represented 57.3% of the variances. Consensus points were found, such as the feeling of being more secure after FMD vaccination campaigns; the fact that farmers take vaccination decisions themselves without being influenced by other stakeholders; the opinion that FMD vaccination is cheaper than the costs of treating a sick animal; and that vaccines provided by governmental authorities are of high quality. Part of the studied population did not consider vaccination to be the first choice strategy in prevention. This raises the question of how to improve the active participation of farmers in the FMD vaccine strategy. Taking into consideration farmers’ perceptions can help to implement feasible vaccination strategies at the local level.
Information-Sharing and Confidentiality in Social Policy: Regulating Multi-Agency Working

In recent years, there has been growing concern in the UK that local services aimed at risky or vulnerable people are ineffective, because of agencies’ persistent failure to share information about their clients. Despite considerable national policy effort to encourage better information-sharing, previous research indicates that there are many cases where information is still not shared when it should be, or where it is shared when it should not be, with potentially devastating results. This article uses data from the largest empirical study of local information-sharing yet undertaken to examine four policy sectors where multi-agency working has come to the fore. It shows that variations in their information-sharing and confidentiality practices can be explained by neo-Durkheimian institutional theory and uses insights from this theory to argue that current policy tools, which emphasize formal regulation, are unlikely to lead to consistent and acceptable outcomes, not least because of unresolved conflicts in values and aims.
Coral—the world's most diverse symbiotic ecosystem

Zooxanthellate corals (i.e. those harbouring Symbiodinium) are the main builders of the world's shallow‐water marine coral reefs. They represent intimate diverse symbioses between coral animals, single‐celled photosynthetic dinoflagellates (Symbiodinium spp.), other microscopic eukaryotes, prokaryotes and viruses. Crabs and other crustaceans, worms, sponges, bivalves and hydrozoans, fishes, sea urchins, octopuses and sea stars are itinerant members of these ‘rainforests of the sea’. This review focuses on the biodiversity of scleractinian coral animals and their best studied microscopic epi‐ and endosymbionts. In relation to coral‐associated species diversity, Symbiodinium internal transcribed spacer region sequence types tally 102–103 or up to ~15 different operational taxonomic units (OTUs, or putative species at the 97% sequence identity level; this cut‐off was chosen based on intragenomic sequence diversity observed in monoclonal cultures) and prokaryotes (mostly bacterial) total 102–104 OTUs. We analysed all publically accessible 16S rRNA gene sequence data and found Gammaproteobacteria were extremely abundant, followed by Alphaproteobacteria. Notably, Archaea were poorly represented and ‘unassigned OTUs’ were abundant in data generated by high‐throughput DNA sequencing studies of corals. We outline and compare model systems that could be used in future studies of the coral holobiont. In our future directions, we recommend a global coral sampling effort including substantial attention being paid to method of coral tissue acquisition, which compartments (mucus, tissue, skeleton) to explore, broadening the holobiont members considered and linking biodiversity with functional investigations.
Fibrosis, not cell size, delineates β-myosin heavy chain reexpression during cardiac hypertrophy and normal aging in vivo

Reexpression of the fetally expressed β-myosin heavy chain (β-MHC) gene is a well documented marker of pathological cardiac hypertrophy and normal aging in many experimental models. To gain insights into factors affecting this reexpression of β-MHC within the complex anatomical structure of the heart, we investigated the spatial pattern of its expression at the level of single cells during aging and hypertrophy. We generated mice that express yellow fluorescent protein fused to the N terminus of the β-MHC and examined its expression pattern during normal aging and in mice with hypertrophy induced by constitutive expression of a renin transgene. The localization of fibrosis within the hearts also was determined by using a fluorescent lectin. The results show that reexpression of β-MHC occurs in discrete subsets of myocytes within the subendocardium rather than uniformly throughout the heart, that β-MHC induction is not an obligatory consequence of cellular hypertrophy, and that β-MHC-expressing cells in the normal aging heart and the hypertrophic heart are distributed predominantly in clusters within and surrounding foci of fibrosis. We conclude that β-MHC gene expression in the normal aging adult and hypertrophic mouse heart is a marker of fibrosis rather than of cellular hypertrophy.
Prevalence and immunohistochemical findings of subclinical kidney allograft rejection and its association with graft outcome

Abstract: Subclinical acute rejection (SAR) occurs in about 30% of stable renal transplant patients and may be a risk factor for a poor allograft outcome. In the present study, the prevalence and clinical features of subclinical rejection, and the expression of immune activation markers in surveillance graft biopsies were assessed and correlated with late graft outcomes. Protocol biopsies were obtained at 2 and 12 months post‐transplant in 32 and 26 patients, respectively, with stable renal function. The Banff 1997 criteria were used for histological diagnosis. Graft function and survival and proteinuria were assessed during the 36 months of follow‐up. Immunohistochemical evaluation of cell subpopulations and immunoactivation markers were performed on protocol biopsies. The prevalence of SAR at 2 months and of chronic allograft nephropathy (CAN) at 12 months in representative biopsies was 55 and 50%, respectively. Patients with SAR presented mononuclear cell infiltration with an increased expression of CD3, CD4, CD68, IL‐2R and granzyme B. Kidney graft function was significantly worse in patients with SAR at 2 months who had chronic rejection on biopsy at 12 months, but SAR was not associated with a worse graft function, greater proteinuria or a lower graft survival in 3 yr of follow‐up. In conclusion, we found an elevated prevalence of SAR at 2 months after transplantation with an increased expression of activation markers. Although an association of SAR with poor graft outcome was not observed, our results suggest that SAR is an immunologically active process and underscore the importance of protocol biopsies in the surveillance of transplanted kidneys.
Measuring Serotonin Distribution in Live Cells with Three-Photon Excitation

Tryptophan and serotonin were imaged with infrared illumination by three-photon excitation (3PE) of their native ultraviolet (UV) fluorescence. This technique, established by 3PE cross section measurements of tryptophan and the monoamines serotonin and dopamine, circumvents the limitations imposed by photodamage, scattering, and indiscriminate background encountered in other UV microscopies. Three-dimensionally resolved images are presented along with measurements of the serotonin concentration (∼50 mM) and content (up to ∼5 × 108 molecules) of individual secretory granules.
Bayesian age-stage modelling of Plasmodium falciparum sequestered parasite loads in severe malaria patients

A discrete-time age-stage model is proposed for estimating the number of sequestered parasites in severe malaria patients. A Bayesian Markov chain Monte Carlo (MCMC) approach is used to model the dynamics of Plasmodium falciparum parasitaemia in 107 paediatric patients in a randomized controlled trial of quinine and artemether in Kenya, in whom 4-hourly peripheral parasitaemia determinations were made. The MCMC approach allows the model to be fitted simultaneously to the entire dataset, providing point and interval estimates for both population and individual patient parameters. Analysis of a simulated dataset indicated that the models gave good estimates of the distribution of parasites between different stages on enrolment, for patients with a wide range of initial states. The analysis of the Kenyan patients suggested that there is considerable variation between patients within the same centre, in both the proportion of sequestered parasites and the intrinsic rate of increase of the parasite population in the absence of treatment. The resulting models should prove a useful tool for cross-validating biochemical approaches for estimating the sequestered load.
Bradykinin as an endogenous myocardial protective substance with particular reference to ischemic preconditioning--a brief review of the evidence.

The present brief review summarizes the evidence for the possibility that endogenously released bradykinin plays a major role in protecting the heart against the consequences of acute myocardial injury. This evidence includes the facts that kinins are generated under myocardial ischemia; that when they are administered, they are cardioprotective (e.g., antiarrhythmic); that drugs that enhance the release of bradykinin from the ischemic heart reduce the ischemic injury and, conversely, drugs that block bradykinin receptors attenuate the reduction in ischemic injury resulting from the release of, or administration of, bradykinin. The possible mechanism of bradykinin in the cardioprotection afforded by ischemic preconditioning is summarized. Ischemic preconditioning can be defined as the marked reduction in the severity of ischemic changes that result from coronary artery occlusion when that occlusion is preceded by brief periods of myocardial ischemia, either regional or global, induced, for example, by complete or partial coronary artery occlusion or by rapid ventricular pacing. The possible mechanisms of cardioprotection elicited by bradykinin (and ischemic preconditioning) are summarized. The most likely is the generation of cyclic GMP within the ischemic myocardium following bradykinin-stimulated nitric oxide generation and release from endothelial cells.
Mortalidad infantil como indicador de desigualdad del sistema de salud chileno

Este trabajo busca documentar la distribucion de la Tasa de Mortalidad Infantil (TMI) a nivel comunal y su relacion causal a factores socio-economicos, demograficos y del sistema de salud. Se utilizaron las estadisticas vitales disponibles en el Departamento de Estadisticas e Informacion de Salud (DEIS) y caracteristicas comunales disponibles en el Sistema Nacional de Informacion Municipal (SINIM), desde el ano 2001 al 2011, para las 345 comunas chilenas. Se construyeron indicadores de desigualdad para mortalidad infantil e ingresos en salud municipal per capita para cada ano y se evaluo su correlacion y evolucion en el periodo. Utilizando modelos de datos de panel se evaluo la asociacion de la tasa de mortalidad infantil a caracteristicas socioeconomicas, sanitarias y de recursos municipales. Los resultados obtenidos muestran que mientras la mediana nacional de TMI por comunas se ha mantenido estable, la desigualdad a nivel comunal en este indicador ha ido en aumento. Mayor tasa de pobreza, menor nivel educacional de la poblacion, no contar con Servicios de Atencion Primaria de Urgencias (SAPU), menor inversion en salud municipal y mayor distancia al hospital base de referencia, resultan ser las principales caracteristicas comunales que generan mayor mortalidad infantil en distintos modelos evaluados, con nivel de confianza sobre el 95%.