Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetics and Pharmacogenomics of Once-Daily Raltegravir and Atazanavir in Healthy Volunteers

ABSTRACT Atazanavir inhibits UDP-glucuronyl-transferase-1A1 (UGT1A1), which metabolizes raltegravir, but the magnitude of steady-state inhibition and role of the UGT1A1 genotype are unknown. Sufficient inhibition could lead to reduced-dose and -cost raltegravir regimens. Nineteen healthy volunteers, age 24 to 51 years, took raltegravir 400 mg twice daily (arm A) and 400 mg plus atazanavir 400 mg once daily (arm B), separated by ≥3 days, in a crossover design. After 1 week on each regimen, raltegravir and raltegravir-glucuronide plasma and urine concentrations were measured by liquid chromatography-tandem mass spectrometry in multiple samples obtained over 12 h (arm A) or 24 h (arm B) and analyzed by noncompartmental methods. UGT1A1 promoter variants were detected with a commercially available kit and published primers. The primary outcome was the ratio of plasma raltegravir Ctau, or concentration at the end of the dosing interval, for arm B (24 h) versus arm A (12 h). The arm B-to-arm A geometric mean ratios (95% confidence interval, P value) for plasma raltegravir Ctau, area under the concentration-time curve from 0 to 12 h (AUC0-12), and raltegravir-glucuronide/raltegravir AUC0-12 were 0.38 (0.22 to 0.65, 0.001), 1.32 (0.62 to 2.81, 0.45), and 0.47 (0.38 to 0.59, <0.001), respectively. Nine volunteers were heterozygous and one was homozygous for a UGT1A1 reduction-of-function allele, but these were not associated with metabolite formation. Although atazanavir significantly reduced the formation of the glucuronide metabolite, its steady-state boosting of plasma raltegravir did not render the Ctau with a once-daily raltegravir dose of 400 mg similar to the Ctau with the standard twice-daily dose. UGT1A1 promoter variants did not significantly influence this interaction.
Prevalência de bullying em uma amostra representativa de adolescentes

Introducao: Bullying e considerado um subtipo de violencia e caracteriza-se por acoes negativas de parte de um ou mais estudantes em uma relacao desigual de poder. Objetivo: verificar a prevalencia do Bullying em uma amostra representativa de adolescentes brasileiros. Metodologia: Estudo epidemiologico transversal de base escolar. Participaram da pesquisa, adolescentes de 11 a 16 anos, matriculados na rede publica de ensino, de um municipio de medio porte do noroeste paulista. A pratica de bullying foi avaliada utilizando o questionario Kidscape . A direcao da escola intermediou a autorizacao dos pais/responsaveis para que estes assinassem o termo de consentimento livre e esclarecido, permitindo assim a participacao de seus filhos na pesquisa. Os dados foram analisados por meio de analise estatistica descritiva e os resultados foram expressos em valores absolutos e relativos. Resultados: no total, 815 adolescentes foram avaliados. A maioria pertencia ao sexo feminino (59,9%) e tinha a cor da pele parda (47,2%). Quase metade (48,22%) dos adolescentes participantes da pesquisa relatou ja ter sido vitima de bullying . A forma mais prevalente de intimidacao sofrida foi a verbal (46,56%) e os episodios ocorreram principalmente dentro da sala de aula (45,55%). A maioria dos agressores eram meninos (65,14%). Grande parte dos estudantes (65,2%) relatou ter sido vitima de bullying mais de uma vez e nunca atuaram como intimidadores (67,7%). Entre os participantes, 46,56% acreditam que a culpa pelos episodios de bullying seja do proprio agressor. Conclusao: houve uma alta taxa de prevalencia de adolescentes vitimas de bullying na populacao estudada. Descritores: Bullying ; Adolescente; Violencia.
Postoperative nausea and vomiting: a review of current literature.

INTRODUCTION Postoperative nausea and vomiting (PONV) is one of the commonest complaints following anaesthesia, and can result in morbidity like wound dehiscence, bleeding, pulmonary aspiration of gastric contents, fluid and electrolyte disturbances, delayed hospital discharge, unexpected hospital admission, and decreased patient satisfaction. METHOD A literature search was done on the Medline and relevant articles chosen. RESULTS Despite the vast amount of research done in this field and the variety of antiemetic drugs available, PONV still has a high incidence. Many factors are associated with PONV. Quantifying the relative impact of risk factors on PONV has resulted in the development of risk models, which can stratify risk categories and hence allow the anaesthetist to identify those patients at higher risk for PONV. The management of PONV requires a multi-modal approach which can include the use of less emetogenic anaesthetic techniques, balanced analgesia, appropriate intravenous hydration, the use of pharmacotherapy and possibly non-pharmacologic methods. CONCLUSIONS The use of risk models facilitates the judicious use of pharmacotherapy to ameliorate PONV especially in the high-risk patient and may lead to a more cost effective and efficient means of managing PONV.
Combined power and rate adaptation for wireless cellular systems

We extend the throughput optimization technique of Qiu and Chawla (1999) for adaptive modulation, to combine power and rate adaptation in wireless cellular systems. We develop new combined power and rate control algorithms for wireless multimedia systems, in which the transmitted powers and rates of different media users are adapted based on the signal-to-interference power ratio. Using simulations, we show that with appropriately chosen power and rate limits, our proposed combined power and rate control algorithms can achieve a higher throughput when compared to previously proposed algorithms with power control only.
Three Sequence Rules for Chromatin

Abstract Extensive DNA sequence analysis of three eukaryotes, S. cerevisiae, C. elegans, and D. melanogaster, reveals two different AA/TT periodical patterns associated with the nucleosome positioning. The first pattern is the counter-phase oscillation of AA and TT dinucleotides, which has been frequently considered as the nucleosome DNA pattern. This represents the sequence rule I for chromatin structure. The second pattern is the in-phase oscillation of the AA and TT dinucleotides with the same nucleosome DNA period, 10.4 bases. This pattern apparently corresponds to curved DNA, that also participates in the nucleosome formation, and represents the sequence rule II for chromatin. The positional correlations of AA and TT dinucleotides also indicate that the nucleosomes are separated by specific linker sizes (preferably 8, 18,…bases), dictated by the steric exclusion rules. Thus, the sequence positions of the neighboring nucleosomes are correlated, and this represents the sequence rule III.
Assembly of a tail-less mutant of the intermediate filament protein, vimentin, in vitro and in vivo.

Recent reports on the possible contribution of the non-alpha-helical carboxy-terminal domain ("tail") of type III intermediate filament (IF) proteins to IF assembly have been controversial. To examine the importance and role of this domain, we have therefore engineered a Xenopus laevis vimentin cDNA to code for a tail-less polypeptide and have used it in combination with prokaryotic and eukaryotic expression systems. Here we show that tail-less vimentin, isolated from transfected bacteria (Escherichia coli), when used for assembly in vitro, forms normal-looking, loosely packed IFs. By viscometry we demonstrate that this tail-less vimentin assembles at an even higher rate and into longer IFs than wild-type vimentin. In vivo, i.e., by forced expression in transfected type III IF-free cultured epithelial cells, tail-less vimentin was also recovered in short fibrillar structures, in rodlets and in small as well as large spheroidal aggregates ("granules") that did not reveal any IF substructure. Surprisingly, however, spheroidal aggregate structures formed from the tail-deleted vimentin, were seen not only in the cytoplasm but also in the nucleus, indicating a role of the tail in higher order organization and compartmentalization of the vimentin IF system.
Developing an advisor predicting inpatient hypokalemia: a negative study.

Introduction Hypokalemia, defined as serum potassium (“K”) levels below 3.5mEq/L, is important clinically. It can cause muscle weakness, renal tubular defects, arrhythmias, and even death. A complex buffering system regulates serum K levels. Diuretics, like furosemide, cause renally mediated K depletion [1]. A previous study detected hypokalemia (lowK) in 21% of inpatients taking furosemide [2]. Despite hypokalemia's significance, a search of PubMed reveals few articles that provide algorithms for forecasting lowK. With the ultimate goal of building an informatics advisor to help clinicians avoid lowK in their patients, authors reasoned that linear regression using recent K measurements might predict incipient hypokalemia, since serum K levels might fall at a different rate after K store depletion. Methods Vanderbilt University Hospital (VUH) is an academic, tertiary care hospital in Nashville, TN. Since 1995, VUH has maintained a locally developed electronic health record (EHR) that includes care provider order entry (CPOE) and patient data repository components. Authors completed a simple epidemiological analysis of the frequency of hypokalemia in patients receiving and not receiving furosemide. With the goal of correlating serum K levels and furosemide ordering, and with IRB approval, authors extracted anonymized data from the data repository systems spanning 8/1999-7/2003 inpatients whose admissions lasted at least 48 hours. Authors defined "simple lowK crossing" as sequential serum K measurements, first above, then below 3.5 mEq/L within a given time period, and “clinically significant lowK crossing" as a serum K measurement above 3.5mEq/L followed immediately by either one measurement below 3.2 mEq/L or followed by 2 or more measurements below 3.5 mEq/L. Authors wrote a PERL script attempting to predict, using linear regression, lowK crossings at “starting points” of 48, 72, 96, 120, and 144 hours into a hospital admission. The linear regression used all measured K levels during the 48 hours prior to each starting point, and projected 24, 48, and 72 hours into the future (after the staring point). If the regression line crossed 3.5mEq/L from above to below, a forecast of “impending lowK” during that future 24-hour time interval was recorded. The regression predictions were compared to the “gold standard” of actual recorded lowK crossings of both types. Algorithm performance was measured through sensitivity, specificity, positive predictive value, and negative predictive value calculations.
Theories about ‘ theories ’ : where is the explanation ?

Waxman and Gelman [1] raise a central issue in cognitive development: whether all knowledge emerges from data. Their answer is ‘no’ – even in early development, the emergence of knowledge depends on rudimentary theories and data. Waxman and Gelman present four arguments to support their ‘child-as-both’ (CB) position.Their arguments, however, have a crucial limitation: no explanation is offered for how these theories come about or what the simpler components of these theories are. Consequently, in contrast to alternative accounts [2], CB fails to explain emergence of the very phenomena it enlists as supportive evidence. Waxman and Gelman [1] argue: ‘As infants and young children establish concepts and acquire words to describe them, they rely on both the (rudimentary) theories that they hold and statistics that they witness’. The description suggests that theories predate both ‘concepts’ and ‘words’. Although this could well be the case, it raises two crucial questions. Without concepts, what is the unit of a theory? And how do theories get there? Are these theories akin to literacy, something that people eventually acquire? Or are theories rather akin to the universal grammar that has been claimed to precede any learning [3]? In the former case, theories emerge from data, and the CB account does not differ from the ‘child-as-data-analyst’ (CDA) account. In the latter case, theories do not emerge from data and the proponents of CB accounts have to explain where the theories come from. Without such answers, CB substitutes an explanation with ‘a simple epistemic device that relieves one of the burden of demonstrating how knowledge got there’ ([4], p. 150). Consider an example provided by Waxman and Gelman as evidence that words refer [5]: 18-month-olds were shown a photograph of an object accompanied by a count noun (‘a whisk’). When asked to extend the word to another photograph of a whisk, to an actual 3D whisk or to both, infants rarely generalized words only to the picture. Waxman and Gelman conclude that these findings are incompatible with the strictly associative account. Why not? Given that the majority of the early nouns are associated with 3D objects and not with pictures (i.e. babies spend more time roaming the world rather than reading picture books), 18-montholds are likely to have more statistics about word-object associations than word-picture associations. Therefore, there is little surprise that a brief experience fails to override hard learned contingencies and such failure is testimony to the power of associations rather than evidence against it. By contrast, by simply stating that ‘words
Relationship of safety climate and safety performance in hospitals.

OBJECTIVE To examine the relationship between measures of hospital safety climate and hospital performance on selected Patient Safety Indicators (PSIs). DATA SOURCES Primary data from a 2004 survey of hospital personnel. Secondary data from the 2005 Medicare Provider Analysis and Review File and 2004 American Hospital Association's Annual Survey of Hospitals. STUDY DESIGN A cross-sectional study of 91 hospitals. DATA COLLECTION Negative binomial regressions used an unweighted, risk-adjusted PSI composite as dependent variable and safety climate scores and controls as independent variables. Some specifications included interpersonal, work unit, and organizational safety climate dimensions. Others included separate measures for senior managers and frontline personnel's safety climate perceptions. PRINCIPAL FINDINGS Hospitals with better safety climate overall had lower relative incidence of PSIs, as did hospitals with better scores on safety climate dimensions measuring interpersonal beliefs regarding shame and blame. Frontline personnel's perceptions of better safety climate predicted lower risk of experiencing PSIs, but senior manager perceptions did not. CONCLUSIONS The results link hospital safety climate to indicators of potential safety events. Some aspects of safety climate are more closely related to safety events than others. Perceptions about safety climate among some groups, such as frontline staff, are more closely related than perceptions in other groups.
Endoscopic Management of Gluteus Medius Tendon Tears

Tears in the gluteus medius and minimus tendons have been recognized as an important cause of recalcitrant greater trochanteric pain syndrome. Because of the frequency of partial-thickness undersurface tears, this relatively unknown pathology is often misdiagnosed and left untreated. Surgery is indicated in case of 4 associated conditions: (i) Failure of conservative treatment with duration of symptoms >6 months; (ii) magnetic resonance imaging showing a tendon tear; (iii) positive ultrasound-guided infiltration test; and (iv) the absence of an evolved fatty degeneration or atrophy of the gluteus medius and minimus muscle. Endoscopic repair of partial or full-thickness tears, with systematic resection of the bony structures implicated in the impingement, and a complete bursectomy appear to give satisfactory results, although these results remain to be confirmed by clinical studies with longer follow-up. The degree of tendon degeneration may compromise the tissue left for reattachment, raising concerns over its healing capacity, durability, and ultimate strength of the repair.
High plasma HIV load in the CRF01-AE outbreak among injecting drug users in Finland

An explosive outbreak of HIV-1 caused by the recombinant subtype AE (CRF01-AE) was detected in 1998 among Finnish injecting drug users (IDUs). These IDUs were compared with IDUs from the Amsterdam Cohort Study (ACS) infected with subtype B, to detect possible differences between 2 western IDU cohorts infected with different subtypes. Markers for progression (viral load and CD4+lymphocyte count) were compared between 93 IDUs with CRF01-AE and 63 IDUs with subtype B. Only persons with a seroconversion interval ≤2 y were included. During 48 months of follow-up, both cohorts were similar in CD4+ cell decline, but the Finnish IDUs had 0.34–0.94 log10 copies/ml higher viral loads. The Amsterdam IDUs had a low viral load (<1000 copies/ml) significantly more often than the Finnish IDUs. The difference could not be explained by the use of antiretrovirals. The higher viral load may have contributed to the rapid spread of the recombinant virus in the Finnish outbreak.
The Socio-Editorial History of the Narrative Works of María de Zayas y Sotomayor

espanolEste estudio reconstruye la historia socio-editorial de las obras narrativas de Maria de Zayas y Sotomayor: Novelas amorosas y ejemplares (1637), Parte segunda del Sarao y entretenimiento honesto (1647), que no fueron los titulos originales que les dio la autora: Honesto y entretenido sarao y Segunda parte del Honesto y entretenido sarao. Esta reconstruccion comienza en el momento en que la autora le envia su obra al librero (editor) para su publicacion, considera el complicado proceso para obtener las licencias necesarias y las intervenciones de los editores e impresores, y tiene como objetivo establecer los textos ideales de la autora. EnglishThis study undertakes a reconstruction of the socio-editorial history of the narrative works of Maria de Zayas y Sotomayor: Novelas amorosas y ejemplares (1637), Parte segunda del Sarao y entretenimiento honesto (1647), which were not the author’s original titles: Honesto y entretenido sarao, and Segunda parte del Honesto y entretenido sarao. Such a reconstruction begins at the moment that the author submits her work to the librero (editor) for publication, considers the complicated process of obtaining the required licenses, and the interventions of the editor(s) and the printers; and has the aim of establishing the author’s ideal texts.
A specific DAMP profile identifies susceptibility to smoke-induced airway inflammation

To the Editor: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality, with a worldwide prevalence of 9–10% [1]. COPD is associated with chronic, neutrophilic inflammation in the lungs, causing destruction of lung parenchyma (emphysema) and/or remodelling of the airways with mucus hypersecretion (bronchitis) [2]. Chronic exposure to noxious particles and gases, such as cigarette smoke, is the major risk factor for COPD, while susceptibility to the disease has a strong genetic component [2]. While the activity of the innate immune system increases with disease progression during early stages of COPD, the precise nature of the factors that trigger innate immune responses in COPD is currently unknown. Cell damage and death upon exposure to cigarette smoke in COPD may induce the release of damage associated molecular patterns (DAMPs) [3]. Elevated levels of several prototypic DAMPs, including high-mobility group box (HMGB)1, heat shock proteins (HSPs) and S100A8, have been observed in bronchoalveolar lavage (BAL) fluid, serum and epithelial lining fluid of COPD patients [4–6]. DAMPs activate cells of the innate immune system upon binding to pattern recognition receptors, such as toll-like receptors (TLRs) and receptor for advanced glycation end-products (RAGE). Importantly, the AGER gene, which encodes the RAGE receptor, is a genome-wide association study susceptibility gene for COPD [7]. To date, studies investigating the role of DAMPs in COPD have focused on the analysis of a single DAMP. However, while each individual DAMP triggers …
Role of Alpha/Beta Interferon in Venezuelan Equine Encephalitis Virus Pathogenesis: Effect of an Attenuating Mutation in the 5′ Untranslated Region

ABSTRACT Venezuelan equine encephalitis virus (VEE) is an important equine and human pathogen of the Americas. In the adult mouse model, cDNA-derived, virulent V3000 inoculated subcutaneously (s.c.) causes high-titer peripheral replication followed by neuroinvasion and lethal encephalitis. A single change (G to A) at nucleotide 3 (nt 3) of the 5′ untranslated region (UTR) of the V3000 genome resulted in a virus (V3043) that was avirulent in mice. The mechanism of attenuation by the V3043 mutation was studied in vivo and in vitro. Kinetic studies of virus spread in adult mice following s.c. inoculation showed that V3043 replication was reduced in peripheral organs compared to that of V3000, titers in serum also were lower, and V3043 was cleared more rapidly from the periphery than V3000. Because clearance of V3043 from serum began 1 to 2 days prior to clearance of V3000, we examined the involvement of alpha/beta interferon (IFN-α/β) activity in VEE pathogenesis. In IFN-α/βR−/− mice, the course of the wild-type disease was extremely rapid, with all animals dying within 48 h (average survival time of 30 h compared to 7.7 days in the wild-type mice). The mutant V3043 was as virulent as the wild type (100% mortality, average survival time of 30 h). Virus titers in serum, peripheral organs, and the brain were similar in V3000- and V3043-infected IFN-α/βR−/− mice at all time points up until the death of the animals. Consistent with the in vivo data, the mutant virus exhibited reduced growth in vitro in several cell types except in cells that lacked a functional IFN-α/β pathway. In cells derived from IFN-α/βR−/− mice, the mutant virus showed no growth disadvantage compared to the wild-type virus, suggesting that IFN-α/β plays a major role in the attenuation of V3043 compared to V3000. There were no differences in the induction of IFN-α/β between V3000 and V3043, but the mutant virus was more sensitive than V3000 to the antiviral actions of IFN-α/β in two separate in vitro assays, suggesting that the increased sensitivity to IFN-α/β plays a major role in the in vivo attenuation of V3043.
Caps-TripleGAN: GAN-Assisted CapsNet for Hyperspectral Image Classification

The increase in the spectral and spatial information of hyperspectral imagery poses challenges in classification due to the fact that spectral bands are highly correlated, training samples may be limited, and high resolution may increase intraclass difference and interclass similarity. In this paper, in order to better handle these problems, a Caps-TripleGAN framework is proposed by exploring the 1-D structure triple generative adversarial network (TripleGAN) for sample generation and integrating CapsNet for hyperspectral image classification. Moreover, spatial information is utilized to verify the learning capacity and discriminative ability of the Caps-TripleGAN framework. The experimental results obtained with three real hyperspectral data sets confirm that the proposed method outperforms most of the state-of-the-art methods.