Miracle-dz/UniFAR-FTUs huggingface dataset:
The Price of Tumor Control: An Analysis of Rare Side Effects of Anti-CTLA-4 Therapy in Metastatic Melanoma from the Ipilimumab Network

Background Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE) in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g. due to bowel perforations. However, the spectrum of less common AEs is expanding as ipilimumab is increasingly applied. Stringent recognition and management of AEs will reduce drug-induced morbidity and costs, and thus, positively impact the cost-benefit ratio of the drug. To facilitate timely identification and adequate management data on rare AEs were analyzed at 19 skin cancer centers. Methods and Findings Patient files (n = 752) were screened for rare ipilimumab-associated AEs. A total of 120 AEs, some of which were life-threatening or even fatal, were reported and summarized by organ system describing the most instructive cases in detail. Previously unreported AEs like drug rash with eosinophilia and systemic symptoms (DRESS), granulomatous inflammation of the central nervous system, and aseptic meningitis, were documented. Obstacles included patientś delay in reporting symptoms and the differentiation of steroid-induced from ipilimumab-induced AEs under steroid treatment. Importantly, response rate was high in this patient population with tumor regression in 30.9% and a tumor control rate of 61.8% in stage IV melanoma patients despite the fact that some patients received only two of four recommended ipilimumab infusions. This suggests that ipilimumab-induced antitumor responses can have an early onset and that severe autoimmune reactions may reflect overtreatment. Conclusion The wide spectrum of ipilimumab-induced AEs demands doctor and patient awareness to reduce morbidity and treatment costs and true ipilimumab success is dictated by both objective tumor responses and controlling severe side effects.
Creutzfeldt‐Jakob disease: Clinical analysis of a consecutive series of 230 neuropathologically verified cases

In this consecutive series of 230 patients with neuropathologically verified Creutzfeldt‐Jakob disease (CJD), the disease was found to affect men and women with approximately equal frequency in a peak plateau between the ages of 55 and 75 years (mean, 61.5 years). Familial cases accounted for 4 to 8% of the total series. Nonspecific prodromal symptoms occurred in one third of the patients, and the neurological presentation, although usually a gradually evolving mental deterioration, was of rapid onset in 20% of patients and in 36% of patients consisted exclusively of neurological symptoms. The great majority of these symptoms were of cerebellar or visual origin. Extrapyramidal muscular rigidity, myoclonus, and characteristic periodic electroencephalographic (EEG) complexes were observed comparatively late in the illness, and some type of involuntary movement or periodic EEG activity was seen in over 95% of the patients. The median duration of illness was 4 months (mean, 7.6 months); 90% of patients died within a year of onset.
Young people's accounts of their experiences with mediated sexual content during childhood and teenage life

Discourses about pornography have grown since the diffusion of print communication and the first erotic representations. In the 80s, the so-called sex wars involved intense debates about pornography s liberating or objectifying nature, while in the 90s, the emergence of porn studies offered a more balanced and contextualized analysis of pornography, highlighting the need for researchers to also focus on the audience s understanding of the experience. Although the majority of research in this field has focused on adults, much of the concern relates to children. To date, however, most of the research relating to children has focused on effects and on potential harm. Audience researchers in Cultural Studies have examined how children understand representations of sex, love and romance, but only in relation to mainstream media. Yet when it comes to pornography in particular, the discussion is to a great extent based on adults assumptions about what is potentially harmful for children. My aim is to approach children s use and interpretation of sexual content in the media through an audience reception approach. In a sense, this brackets off the question of possible risk or harm, in favour of focusing on the nature of the experience itself. My research is based on interviews conducted with young adults (18-22 years old) thinking retrospectively about their experiences with sexual content in childhood and early teenage life. Despite the number of disadvantages this approach may have, this thesis aims to focus on how participants themselves report and account for their actual experiences. Using a basic thematic coding, I consider the self-reported nature and context of young people s experiences. Next, I focus on the discourses used to interpret and contextualize their experiences. Finally, through a narrative approach I examine their constructions of identities in talking about sexuality. In these ways, this thesis wishes to offer new insights into the topic through an audience reception approach that until now has been largely missing from the academic agenda.
Very early pattern of movement disorders in sepiapterin reductase deficiency

Sepiapterin reductase deficiency (SRD; Online Mendelian Inheritance in Man *182125) is a rare disorder of biogenic amines synthesis caused by mutations of the SPR gene on chromosome 2p14-p12.1 The most common presenting symptoms of SRD are developmental delay and axial hypotonia.2 The few patients observed during the very early stage of the disease suggested a peculiar pattern of neurologic impairment.3,4 With the aim of contributing to this topic, we report on a new case diagnosed and treated since the first months of life.
A neuroscientific approach to choice modeling: Electroencephalogram (EEG) and user preferences

Discrete choice experiments have traditionally focused on improving the prediction of static choices that are measured through external reflection and surveys. It is argued that considering the underlying processes of decision making across a variety of contexts may further progress decision research. As a pilot study in this field, this paper explores the dynamic nature of decision-making by examining the associated brain activity, Electroencephalogram (EEG), of people while undertaking choices designed to elicit their preferences. To facilitate such a study, the Tobii-Studio eye tracker system was utilized to capture the participants' choice based preferences when they were observing seventy two sets of objects of three images offering potential personal computer backgrounds. Choice based preferences were identified by having the respondent click on their preferred image. In addition, the commercial Emotiv wireless EEG headset with 14 channels was utilized to capture the associated brain activity during the period of the experiments. Principal Component Analysis (PCA) was utilized to preprocess the EEG data before analyzing it with the Fast Fourier Transform (FFT) to observe the changes in the four principal frequency bands, theta (3 - 7 Hz), alpha (8 - 12 Hz), beta (13 - 30 Hz), and gamma (30 - 40 Hz). A mutual information (MI) measure was then used to study left-to-right hemisphere differences as well as front-to-back difference. Across six recruited participants there was a clear and significant change in the spectral activities taking place mainly in the frontal (theta and alpha across F3 and F4) and occipital (alpha and beta across O1 and O2) regions while the participants were indicating their preferences.
Screening for Problematic Worry in Adults With a Single Item From the Penn State Worry Questionnaire

As the rapid assessment of mental health is a growing need, a quick and valid tool for the early detection of symptoms that can be flexibly deployed across a range of contexts may be especially beneficial. This is particularly true of anxiety problems, which when undetected contribute to health care costs and lost work productivity. Data from more than 10,000 respondents (primarily female undergraduates) were used to test whether a single item from the popular Penn State Worry Questionnaire could serve as a screening tool in settings where administration of the full scale is undesirable. Items were evaluated by examining item response theory models, screening capabilities, stability over time, convergence with other anxiety and depression measures, and a response time analysis that assessed how quickly participants responded to each item. Item 15 (“I worry all the time”) emerged as the strongest item: It was the most discriminating and reliable item, had sensitivity and specificity similar to the full scale, had the highest 1-month and 1-year retest coefficients, the highest convergent correlations with measures of anxiety and depression, and was responded to significantly faster than any other item. We suggest that in time-limited contexts, this item is suitable for screening.
Targeted RNA-Sequencing with Competitive Multiplex-PCR Amplicon Libraries

Whole transcriptome RNA-sequencing is a powerful tool, but is costly and yields complex data sets that limit its utility in molecular diagnostic testing. A targeted quantitative RNA-sequencing method that is reproducible and reduces the number of sequencing reads required to measure transcripts over the full range of expression would be better suited to diagnostic testing. Toward this goal, we developed a competitive multiplex PCR-based amplicon sequencing library preparation method that a) targets only the sequences of interest and b) controls for inter-target variation in PCR amplification during library preparation by measuring each transcript native template relative to a known number of synthetic competitive template internal standard copies. To determine the utility of this method, we intentionally selected PCR conditions that would cause transcript amplification products (amplicons) to converge toward equimolar concentrations (normalization) during library preparation. We then tested whether this approach would enable accurate and reproducible quantification of each transcript across multiple library preparations, and at the same time reduce (through normalization) total sequencing reads required for quantification of transcript targets across a large range of expression. We demonstrate excellent reproducibility (R2 = 0.997) with 97% accuracy to detect 2-fold change using External RNA Controls Consortium (ERCC) reference materials; high inter-day, inter-site and inter-library concordance (R2 = 0.97–0.99) using FDA Sequencing Quality Control (SEQC) reference materials; and cross-platform concordance with both TaqMan qPCR (R2 = 0.96) and whole transcriptome RNA-sequencing following “traditional” library preparation using Illumina NGS kits (R2 = 0.94). Using this method, sequencing reads required to accurately quantify more than 100 targeted transcripts expressed over a 107-fold range was reduced more than 10,000-fold, from 2.3×109 to 1.4×105 sequencing reads. These studies demonstrate that the competitive multiplex-PCR amplicon library preparation method presented here provides the quality control, reproducibility, and reduced sequencing reads necessary for development and implementation of targeted quantitative RNA-sequencing biomarkers in molecular diagnostic testing.
Racial disparities in perinatal outcomes among women with gestational diabetes.

BACKGROUND We sought to evaluate perinatal outcomes by race/ethnicity among women with gestational diabetes mellitus (GDM). METHODS We conducted a 14-year retrospective cohort study of women with GDM. Selected perinatal outcomes were examined. Unadjusted and adjusted prevalence ratios (PR, aPR) of perinatal outcomes, comparing Hispanic and African American women with Caucasian women, were calculated. RESULTS Hispanics comprised 54% of the 1018 woman cohort. Half received medical management of GDM (52%), more than African Americans (45%) or Caucasians (39%)(p<0.05). Compared with Caucasians, Hispanics had fewer deliveries <37 weeks (aPR 0.58, 95% confidence interval [CI] 0.42-0.81), less gestational hypertension (aPR 0.43, 95% CI 0.22-0.83), larger median birth weight infants (3453 g vs 3291 g, p<0.05), and greater risk of shoulder dystocia (aPR 3.52, 95% CI 1.30-9.50). Hispanic women had fewer adverse outcomes overall compared with Caucasian or African American women. CONCLUSIONS We report differences between Hispanic and Caucasian women with GDM. Treatment to achieve glycemic control and reduce adverse outcomes may differ by race/ethnicity.
The evolution of star formation activity in galaxy groups

We study the evolution of the total star formation (SF) activity, total stellar mass (ΣM*) and halo occupation distribution (HOD) in massive haloes by using one of the largest X-ray selected sample of galaxy groups with secure spectroscopic identification in the major blank field surveys (ECDFS, CDFN, COSMOS, AEGIS). We provide an accurate measurement of star formation rate (SFR) for the bulk of the star-forming galaxies using very deep mid-infrared Spitzer MIPS and far-infrared Herschel PACS observations. For undetected IR sources, we provide a well-calibrated SFR from spectral energy distribution (SED) fitting. We observe a clear evolution in the level of SF activity in galaxy groups. The total SF activity in the high-redshift groups (0.5 < z < 1.1) is higher with respect to the low-redshift (0.15 < z < 0.5) sample at any mass by 0.8 ± 0.12 dex. A milder difference (0.35 ± 0.1 dex) is observed between the low-redshift bin and the groups at z ∼ 0. We show that the level of SF activity is declining more rapidly in the more massive haloes than in the more common lower mass haloes. We do not observe any evolution in the HOD and total stellar mass–halo mass relations in groups. The picture emerging from our findings suggests that the galaxy population in the most massive systems is evolving faster than galaxies in lower mass haloes, consistently with a ‘halo downsizing’ scenario.
The Differences between Recommender Technologies in their Impact on Sales Diversity

Recommender systems are frequently used as part of online shops to help consumers browse through large product offerings by recommending those products which are the most relevant for them. Although consumers’ interactions with recommender systems have been subject to substantial research, it is still unclear what the effect on aggregated sales diversity is, i.e. whether this leads to predominance of fast-selling or niche products. It is also unclear, whether any potential effects would differ between specific recommender technologies. We created a realistic web-experiment to monitor consumer behavior while purchasing digital music tracks when different recommender technologies are present. To analyze potential changes in sales diversity we used the Gini coefficient as well as additional measures. We found that sales diversity increases for all recommender technologies, except for bestseller lists. Furthermore, the differences across recommender technologies are rather small. Our findings have significant implications for online retailers and for producers.
Autonomous orbit determination via kalman filtering of gravity gradients

Spaceborne gravity gradients are proposed in this paper to provide autonomous orbit determination capabilities for near Earth satellites. The gravity gradients contain useful position information, which can be extracted by matching the observations with a precise gravity model. The extended Kalman filter (EKF) is investigated as the principal estimator. The stochastic model of orbital motion, the measurement equation, and the model configuration are discussed for the filter design. An augmented state filter is also developed to deal with unknown significant measurement biases. Simulations are conducted to analyze the effects of initial errors, data-sampling periods, orbital heights, attitude and gradiometer noise levels, and measurement biases. Results show that the filter performs well with additive white noise observation errors. Degraded observability for the along-track position is found for the augmented state filter. Real flight data from the GOCE (gravity field and steady-state ocean circulation explorer) satellite are used to test the algorithm. Radial and cross-track position errors of less than 100 m have been achieved.
[Health inequalities in Korea: current conditions and implications].

OBJECTIVES The aim of this study is to summarize the current conditions and implications of health inequalities in South Korea. METHODS Through a literature review of empirical studies and supplementary analysis of the data presented in the 1998, 2001, and 2005 KNHANEs, we evaluated the extent and trends of socioeconomic inequalities in both health risk factors, such as smoking, physical activity, and obesity, and outcomes, such as total mortality, subjective poor health status by self-reports and metabolic syndrome. Relative risks and odds ratios were used to measure differences across socioeconomic groups, and the relative index of inequality was used to evaluate the changes in inequalities over time. RESULTS We found clear inequalities to various degrees in most health indicators. While little change was observed in mortality differences over time, the socioeconomic gaps in risk factors and morbidity have been widening, with much larger differences among the younger population. CONCLUSIONS Socioeconomic inequalities are pervasive across various health indicators, and some of them are increasing. The trends in socioeconomic inequalities in health should be carefully monitored, and comprehensive measures to alleviate health inequalities are needed, especially for young populations.
Pengaruh Kepemilikan Manajerial, Kepemilikan Institusional, Kebijakan Hutang, Profitabilitas dan Ukuran Perusahaan terhadap Kebijakan Dividen

ABSTRAKSI Tujuan penelitian ini adalah menemukan bukti empiris pengaruh kepemilikan manajerial, kepemilikan institusional, kebijakan utang, profitabilitas, dan ukuran perusahaan terhadap kebijakan dividen. Penelitian ini menggunakan perusahaan go public yang terdaftar di Bursa Efek Indonesia (BEI), sesuai dengan pengklasifikasian Indonesian Capital Market Dictionary (ICMD) periode 2007- 2009. Teknik pengambilan sampel yang digunakan yaitu purposive sampling. Jumlah sampel akhir yang digunakan yaitu 80 sampel. Teknik analisis regresi berganda digunakan dalam menganalisis data. Hasil penelitian ini menunjukkan bahwa kebijakan utang (Debt to Asset Ratio) Kepemilikan manajerial, kepemilikan institusional dan ukuran perusahaan berpengaruh negatif terhadap kebijakan dividen. Akan tetapi profitabilitas berpengaruh signifikan terhadap kebijakan dividen namun dengan arah positif. Kebijakan hutang tidak memiliki pengaruh terhadap kebijakan dividen. Kata kunci: Kepemilikan manajerial, kepemilikan institusional, kebijakan utang, profitabilitas, ukuran perusahaan, kebijakan dividen.
A Novel Multiple Objective Optimization Framework for Constraining Conductance-Based Neuron Models by Experimental Data

We present a novel framework for automatically constraining parameters of compartmental models of neurons, given a large set of experimentally measured responses of these neurons. In experiments, intrinsic noise gives rise to a large variability (e.g., in firing pattern) in the voltage responses to repetitions of the exact same input. Thus, the common approach of fitting models by attempting to perfectly replicate, point by point, a single chosen trace out of the spectrum of variable responses does not seem to do justice to the data. In addition, finding a single error function that faithfully characterizes the distance between two spiking traces is not a trivial pursuit. To address these issues, one can adopt a multiple objective optimization approach that allows the use of several error functions jointly. When more than one error function is available, the comparison between experimental voltage traces and model response can be performed on the basis of individual features of interest (e.g., spike rate, spike width). Each feature can be compared between model and experimental mean, in units of its experimental variability, thereby incorporating into the fitting this variability. We demonstrate the success of this approach, when used in conjunction with genetic algorithm optimization, in generating an excellent fit between model behavior and the firing pattern of two distinct electrical classes of cortical interneurons, accommodating and fast-spiking. We argue that the multiple, diverse models generated by this method could serve as the building blocks for the realistic simulation of large neuronal networks.
Dynamics of Circulating Progesterone Concentrations Before and During Luteolysis: A Comparison Between Cattle and Horses1

ABSTRACT The profile of circulating progesterone concentration is more dynamic in cattle than in horses. Greater prominence of progesterone fluctuations in cattle than in horses reflect periodic interplay in cattle between pulses of a luteotropin (luteinizing hormone; LH) and pulses of a luteolysin (prostaglandin F2alpha; PGF2alpha). A dose of PGF2alpha that induces complete regression of a mature corpus luteum with a single treatment in cattle or horses is an overdose. The overdose effects on the progesterone profile in cattle are an immediate nonphysiological increase taking place over about 30 min, a decrease to below the original concentration, a dose-dependent rebound 2 h after treatment, and a progressive decrease until the end of luteolysis. An overdose of PGF2alpha in horses results in a similar nonphysiological increase in progesterone followed by complete luteolysis; a rebound does not occur. An overdose of PGF2alpha and apparent lack of awareness of the rebound phenomenon has led to faulty interpretations on the nature of spontaneous luteolysis. A transient progesterone suppression and a transient rebound occur within the hours of a natural PGF2alpha pulse in cattle but not in horses. Progesterone rebounds are from the combined effects of an LH pulse and the descending portion of a PGF2alpha pulse. A complete transitional progesterone rebound occurs at the end of preluteolysis and the beginning of luteolysis and returns progesterone to its original concentration. It is proposed that luteolysis does not begin in cattle until after the transitional rebound. During luteolysis, rebounds are incomplete and gradually wane. A partial rebound during luteolysis in cattle is associated with a concomitant increase in luteal blood flow. A similar increase in luteal blood flow does not occur in mares.