Miracle-dz/UniFAR-FTUs huggingface dataset:
The randomized discontinuation trial: a phase II design to assess growth-inhibitory agents

An increasing number of putative anticancer targets and drugs have been identified with many of these expected to be growth inhibitory. Clinical development of these agents in the phase II setting is challenging because tumor shrinkages, or at least tumor shrinkages that meet the standard definitions of objective response, are not expected. Time to progression end points are however problematic because expected times in the absence of therapy (the null hypothesis) cannot be predicted accurately, thus requiring trials to enroll a concurrent control group. Another problem is that the patient population that will benefit from a new drug remains poorly defined in early-phase development. The randomized discontinuation trial design addresses both of these issues. All patients are initially treated with the drug; patients with an objective response continue therapy; patients who do not progress or experience excess toxicity within a prespecified “run-in” period are then randomized to continuing or discontinuing therapy in a double-blind, placebo controlled manner. Despite certain limitations that need to be recognized, the ability of this design to “select” a cohort most likely to benefit and to rigorously evaluate the disease-stabilizing activity of an investigational agent provides multiple advantages. [Mol Cancer Ther 2007;6(4):1180–5]
Serum glucose level and diabetes predict tissue plasminogen activator-related intracerebral hemorrhage in acute ischemic stroke.

BACKGROUND AND PURPOSE Five pretreatment variables (P<0.1 univariate analysis), including serum glucose (>300 mg/dL), predicted symptomatic intracerebral hemorrhage (ICH) in the National Institute of Neurological Disorders and Stroke rtPA trial. We retrospectively studied stroke patients treated <3 hours from onset with intravenous rtPA at 2 institutions to evaluate the role of these variables in predicting ICH. METHODS Baseline characteristics, including 5 prespecified variables (age, baseline glucose, smoking status, National Institutes of Health Stroke Scale [NIHSS] score, and CT changes [>33% middle cerebral artery territory hypodensity]), were reviewed in 138 consecutive patients. Variables were evaluated by logistic regression as predictors of all hemorrhage (including hemorrhagic transformation) and symptomatic hemorrhage on follow-up CT scan. Variables significant at P<0.25 level were included in a multivariate analysis. Diabetes was substituted for glucose in a repeat analysis. RESULTS Symptomatic hemorrhage rate was 9% (13 of 138). Any hemorrhage rate was 30% (42 of 138). Baseline serum glucose (5.5-mmol/L increments) was the only independent predictor of both symptomatic hemorrhage [OR, 2.26 (CI, 1.05 to 4.83), P=0.03] and all hemorrhage [OR, 2.26 (CI, 1.07 to 4.69), P=0.04]. Serum glucose >11.1 mmol/L was associated with a 25% symptomatic hemorrhage rate. Baseline NIHSS (5-point increments) was an independent predictor of all hemorrhage only [OR, 12.42 (CI, 1.64 to 94.3), P=0.01]. Univariate analysis demonstrated a trend for nonsmoking as a predictor of all hemorrhage [OR, 0.45 (CI, 0.19 to 1. 08), P=0.07]. Diabetes was also an independent predictor of ICH when substituted for glucose in repeat analysis. CONCLUSIONS Serum glucose and diabetes were predictors of ICH in rtPA-treated patients. This novel association requires confirmation in a larger cohort.
Effect of mild hypothermia on ischemia-induced release of neurotransmitters and free fatty acids in rat brain.

We have demonstrated previously that mild intraischemic hypothermia confers a marked protective effect on the final histopathological outcome. The present study was carried out to evaluate whether this protective effect involves changes in the degree of local cerebral blood flow reductions, tissue accumulation of free fatty acids, or alterations in the extracellular release of glutamate and dopamine. Rats whose intraischemic brain temperature was maintained at 36 degrees C, 33 degrees C, or 30 degrees C were subjected to 20 minutes of ischemia by four-vessel occlusion combined with systemic hypotension. Levels of local cerebral blood flow, as measured autoradiographically, were reduced uniformly in all experimental animals at the end of ischemia by gas chromatography after tissue extraction and separation by thin layer chromatography. A massive ischemia-induced accumulation of individual free fatty acids was observed in animal groups whose intraischemic brain temperature was maintained at either 36 degrees C or 30 degrees C. Extracellular neurotransmitter levels were measured by microdialysis; the perfusate was collected before, during, and after ischemia. In rats whose intraischemic brain temperature was maintained at 36 degrees C, dopamine and glutamate increased significantly during ischemia and the early period of recirculation (by 500-fold and sevenfold, respectively). In animals whose brain temperature was maintained at 33 degrees C and 30 degrees C, the release of glutamate was completely inhibited, and the release of dopamine was significantly attenuated (by 60%). These results suggest that mild intraischemic hypothermia does not affect the ischemia-induced local cerebral blood flow reduction or free fatty acid accumulation. (ABSTRACT TRUNCATED AT 250 WORDS)
Direct and indirect vitamin A supplementation strategies result in different plasma and tissue retinol kinetics in neonatal rats

Many questions remain regarding vitamin A (VA) supplementation of infants. Herein we compared direct oral VA supplementation of the neonate and indirect treatment through maternal dietary VA (M-VA) treatment on VA status and kinetics in neonatal rats. Treatments included direct VA combined with retinoic acid (RA) [D-VARA; VA (6 mg/kg) + 10% RA, given orally to neonates on postnatal day (P)2 and P3] and indirect VA supplementation through increased M-VA, compared with each other and oil-treated neonates. [3H]retinol was administered orally to all neonates on P4. Plasma and tissue [3H]retinol kinetics were determined from 1 h to 14 days post-dosing. D-VARA versus placebo dramatically increased liver and lung retinol, but only in the first 8–10 days. In M-VA neonates, liver and lung VA increased progressively throughout the study. Compartmental modeling of plasma [3H]retinol showed that both D-VARA and indirect M-VA reduced retinol recycling between plasma and tissues. Compartmental models of individual tissues predicted that D-VARA stimulated the uptake of VA in chylomicrons to extrahepatic tissues, especially intestine, while the uptake was not observed in M-VA neonates. In conclusion, indirect maternal supplementation had a greater sustained effect than D-VARA on neonatal VA status, while also differentially affecting plasma and tissue retinol kinetics.
The Association of Central Corneal Thickness with Ocular and General Parameters in a Community Setting: The Yazd Eye Study

Purpose: To assess central corneal thickness (CCT) and its associations in an adult Iranian population. Methods: This was a population-based cross-sectional study of adults aged 40–80 years. Eyes with corneal disorders, previous ocular surgery, or trauma were excluded. All subjects underwent complete ophthalmic examination, general health assessment, laboratory tests, and a detailed interview. CCT was measured with an ultrasonic pachymeter. Intraocular pressure (IOP) was measured with Goldmann applanation tonometry. Except for the report on interocular differences in CCT, only one eye of each subject was used for the rest of statistical analyses. Results: The mean age (±SD) of the 1203 participants, who had CCT measurements and met inclusion criteria, was 51.8 ± 8.5 years. The mean CCT was 544 ± 35, 564 ± 28, and 544 ± 36 μm in the eyes of the normal, ocular hypertension, and glaucoma groups, respectively (P = 0.025). In participants without glaucoma, the mean interocular difference in CCT was 9 ± 12 μm. CCT was not significantly associated with age, sex, or some select systemic factors (body mass index, diabetes, hypertension, and renal failure). While controlling for age and sex, CCT was greater in individuals with higher IOPs (P < 0.001), larger vertical or horizontal cup-to-disc ratios (P = 0.044, and P= 0.025, respectively), and hyperopia (P = 0.009). Conclusion: In this adult Iranian population, CCT was significantly associated with IOP, cup-to-disc ratio, and the refractive status of eye. CCT outside the normal range of 475–613 μm or with interocular asymmetry greater than 33 μm (6%) should prompt evaluation for potential ocular disorders.
Electrophysiological effects of intravitreal Avastin (bevacizumab) in the treatment of exudative age-related macular degeneration

Objective: To examine the sensitivity of the multifocal electroretinogram (mf-ERG) at measuring changes in retinal electrical activity in response to Avastin (bevacizumab) treatment for age-related macular degeneration (ARMD). Methods: Nine subjects with exudative ARMD, not previously treated with bevacizumab in the investigated eye, underwent pretreatment testing with mf-ERG and intravenous fluorescein angiography (IVFA). A second mf-ERG test was conducted post-treatment. The P1 response amplitudes were examined for the hexagons corresponding to areas of pathology on the IVFA. Intertest variability was accounted for by examining areas without pathology. Aggregate responses were also generated for central and lesion-associated responses. Results: Changes in P1 response amplitude correlated with changes in visual acuity (R2>0.96). An improvement in Snellen visual acuity correlated with a significant improvement in P1 response amplitude from lesion associated recordings (p<0.03). Changes in P1 response amplitudes were not observed when aggregate responses were generated. Conclusion: This study represents a novel method for assessing an improvement of mf-ERG responses. This is the first study to demonstrate a statistically significant change in retinal electrical activity postbevacizumab in patients with ARMD. This study demonstrates a method for utilising mf-ERG to assess changes in retinal electrical activity and to assess the effectiveness of treatments such as bevacizumab.
Mesoscale Self-Assembly of Hexagonal Plates Using Lateral Capillary Forces: Synthesis Using the "Capillary Bond"

This paper examines self-assembly in a quasi-two-dimensional, mesoscale system. The system studied here involves hexagonal plates (“hexagons”) of poly(dimethylsiloxane) (PDMS; 5.4 mm in diameter, 0.9−2.0 mm thick), with faces functionalized to be hydrophilic or hydrophobic, floating at the interface between perfluorodecalin (PFD) and H2O. The hexagons assemble by capillary forces originating in the interactions of the menisci at their hydrophobic and hydrophilic rectangular faces. The strength and directionality of the interactions can be tailored by manipulating the heights of the faces, the pattern of the hydrophobic faces, the pattern of hydrophobic regions on these faces, and the densities of the three interacting phases (organic liquid, aqueous liquid, polymeric solid). Examination of all 14 possible combinations of hydrophobic and hydrophilic faces on the hexagonal plates led to three outcomes: (i) the extension of the strategies of self-assembly from the molecular to the mesoscale, (ii) the demons.
Robust, Lexicalized Native Language Identification

Previous approaches to the task of native language identification (Koppel et al., 2005) have been limited to small, within-corpus evaluations. Because these are restrictive and unreliable, we apply cross-corpus evaluation to the task. We demonstrate the efficacy of lexical features, which had previously been avoided due to the within-corpus topic confounds, and provide a detailed evaluation of various options, including a simple bias adaptation technique and a number of classifier algorithms. Using a new web corpus as a training set, we reach high classification accuracy for a 7-language task, performance which is robust across two independent test sets. Although we show that even higher accuracy is possible using crossvalidation, we present strong evidence calling into question the validity of cross-validation evaluation using the standard dataset.
Finite time singularity for the modified SQG patch equation

It is well known that the incompressible Euler equations in two dimensions have globally regular solutions. The inviscid surface quasi-geostrophic (SQG) equation has a Biot-Savart law which is one derivative less regular than in the Euler case, and the question of global regularity for its solutions is still open. We study here the patch dynamics in the half-plane for a family of active scalars which interpolates between these two equations, via a parameter α ∈ [0, 12 ] appearing in the kernels of their Biot-Savart laws. The values α = 0 and α = 12 correspond to the 2D Euler and SQG cases, respectively. We prove global in time regularity for the 2D Euler patch model, even if the patches initially touch the boundary of the half-plane. On the other hand, for any sufficiently small α > 0, we exhibit initial data which lead to a singularity in finite time. Thus, these results show a phase transition in the behavior of solutions to these equations, and provide a rigorous foundation for classifying the 2D Euler equations as critical. ∗Department of Mathematics, Rice University, 6100 S. Main St., Houston, TX 77005-1892; kiselev@rice.edu †Department of Mathematics, Stanford University, Stanford, CA 94305; ryzhik@math.stanford. edu ‡School of Mathematics, Georgia Institute of Technology, 686 Cherry Street, Atlanta, GA 30332-0160; yaoyao@math.gatech. edu §Department of Mathematics, University of Wisconsin, 480 Lincoln Dr. Madison, WI 53706-1325; zlatos@math.wisc. edu
Job strain, social support in the workplace, and haemoglobin A1c in Japanese men

OBJECTIVES To examine the association between job strain (defined in the model of job demands and job control) and social support at the workplace with levels of glycosylated haemoglobin A1c (HbA1c) METHODS All male employees aged 40–60 in a manufacturing firm, Japan, were invited to take part in the study. A blood sample was taken from the participants and HbA1c (%) was measured. Job strain and social support at the workplace were assessed with the job content questionnaire (JCQ). After excluding those who had a history of diabetes mellitus or other chronic diseases, data from 268 male day workers were analyzed. RESULTS Age adjusted average concentrations of HbA1c were significantly higher in the highest quartile group of job strain or the lowest quartile group of social support at the workplace (p<0.05). Multiple linear regression analysis indicated that job strain was significantly and positively related to HbA1c (p<0.05), whereas social support at the workplace was significantly and negatively related to HbA1c (p<0.05), both after controlling for other covariates. CONCLUSIONS Greater job strain and lower social support at the workplace may be associated with increased concentrations of HbA1c. Increased blood glucose may be a physiological mediator between job strain or social support at the workplace and coronary heart disease.
VIIRS Reflective Solar Bands Calibration Progress and Its Impact on Ocean Color Products

The radiometric calibration for the reflective solar bands (RSB) of the Visible Infrared Imaging Radiometer Suite (VIIRS) on board the Suomi National Polar-orbiting Partnership (SNPP) platform has reached a mature stage after four years since its launch. The characterization of the vignetting effect of the attenuation screens, the bidirectional reflectance factor of the solar diffuser, the degradation performance of the solar diffuser, and the calibration coefficient of the RSB have all been made robust. Additional investigations into the time-dependent out-of-band relative spectral response and the solar diffuser degradation non-uniformity effect have led to newer insights. In particular, it has been demonstrated that the solar diffuser (SD) degradation non-uniformity effect induces long-term bias in the SD-calibration result. A mitigation approach, the so-called Hybrid Method, incorporating lunar-based calibration results, successfully restores the calibration to achieve ~0.2% level accuracy. The successfully calibrated RSB data record significantly impacts the ocean color products, whose stringent requirements are especially sensitive to calibration accuracy, and helps the ocean color products to reach maturity.
Oxytocin and mutual communication in mother-infant bonding

Mother-infant bonding is universal to all mammalian species. In this review, we describe the manner in which reciprocal communication between the mother and infant leads to mother-infant bonding in rodents. In rats and mice, mother-infant bond formation is reinforced by various social stimuli, such as tactile stimuli and ultrasonic vocalizations (USVs) from the pups to the mother, and feeding and tactile stimulation from the mother to the pups. Some evidence suggests that mother and infant can develop a cross-modal sensory recognition of their counterpart during this bonding process. Neurochemically, oxytocin in the neural system plays a pivotal role in each side of the mother-infant bonding process, although the mechanisms underlying bond formation in the brains of infants has not yet been clarified. Impairment of mother-infant bonding, that is, deprivation of social stimuli from the mother, strongly influences offspring sociality, including maternal behavior toward their own offspring in their adulthood, implying a “non-genomic transmission of maternal environment,” even in rodents. The comparative understanding of cognitive functions between mother and infants, and the biological mechanisms involved in mother-infant bonding may help us understand psychiatric disorders associated with mother-infant relationships.
Boosting an associative classifier

Associative classification is a new classification approach integrating association mining and classification. It becomes a significant tool for knowledge discovery and data mining. However, high-order association mining is time consuming when the number of attributes becomes large. The recent development of the AdaBoost algorithm indicates that boosting simple rules could often achieve better classification results than the use of complex rules. In view of this, we apply the AdaBoost algorithm to an associative classification system for both learning time reduction and accuracy improvement. In addition to exploring many advantages of the boosted associative classification system, this paper also proposes a new weighting strategy for voting multiple classifiers.
Covariance‐regularized regression and classification for high dimensional problems

Summary. We propose covariance‐regularized regression, a family of methods for prediction in high dimensional settings that uses a shrunken estimate of the inverse covariance matrix of the features to achieve superior prediction. An estimate of the inverse covariance matrix is obtained by maximizing the log‐likelihood of the data, under a multivariate normal model, subject to a penalty; it is then used to estimate coefficients for the regression of the response onto the features. We show that ridge regression, the lasso and the elastic net are special cases of covariance‐regularized regression, and we demonstrate that certain previously unexplored forms of covariance‐regularized regression can outperform existing methods in a range of situations. The covariance‐regularized regression framework is extended to generalized linear models and linear discriminant analysis, and is used to analyse gene expression data sets with multiple class and survival outcomes.
Criterion validity of a competency-based assessment center in medical education – a 4-year follow-up study

Introduction Core competencies have progressively gained importance in medical education. In other contexts, especially personnel selection and development, assessment centers (ACs) are used to assess competencies, but there is only a limited number of studies on competency-based ACs in medical education. To the best of our knowledge, the present study provides the first data on the criterion-related validity of a competency-based AC in medical education. Methods We developed an AC tailored to measure core competencies relevant to medical education (social-ethical, communicative, self, and teaching) and tested its validity in n=30 first-year medical students using 3- to 4-year follow-up measures such as (a) objective structured clinical examinations (OSCE) on basic clinical skills (n=26), (b) OSCE on communication skills (n=21), and (c) peer feedback (n=18). The AC contained three elements: interview, group discussion, and role play. Additionally, a self-report questionnaire was provided as a basis for the interview. Results Baseline AC average score and teaching competency correlated moderately with the communication OSCE average score (r=0.41, p=0.03, and r=0.38, p=0.04, respectively). Social-ethical competency in the AC showed a very strong convergent association with the communication OSCE average score (r=0.60, p<0.01). The AC total score also showed a moderate correlation with the overall peer feedback score provided in Year 4 (r=0.38, p=0.06). In addition, communicative competency correlated strongly with the overall peer feedback (r=0.50, p=0.02). We found predominantly low and insignificant correlations between the AC and the OSCE on basic clinical skills (r=−0.33 to 0.30, all p's>0.05). Conclusion The results showed that competency-based ACs can be used at a very early stage of medical training to successfully predict future performance in core competencies.
Tonal consonance parameters link microscopic and macroscopic properties of music exposing a hidden order in melody

Consonance is related to the perception of pleasantness arising from a combination of sounds and has been approached quantitatively using mathematical relations, physics, information theory, and psychoacoustics. Tonal consonance is present in timbre, musical tuning, harmony, and melody, and it is used for conveying sensations, perceptions, and emotions in music. It involves the physical properties of sound waves and is used to study melody and harmony through musical intervals and chords. From the perspective of complexity, the macroscopic properties of a system with many parts frequently rely on the statistical properties of its constituent elements. Here we show how the tonal consonance parameters for complex tones can be used to study complexity in music. We apply this formalism to melody, showing that melodic lines in musical pieces can be described in terms of the physical properties of melodic intervals and the existence of an entropy extremalization principle subject to psychoacoustic macroscopic constraints with musical meaning. This result connects the human perception of consonance with the complexity of human creativity in music through the physical properties of the musical stimulus.
Motivation for giving birth after breast cancer

Background: Breast cancer at a young age threatens the natural developmental tasks that characterize this phase in life including parenthood. The dilemma of whether to give birth arises due to the potential medical, psychological and social implications of pregnancy, birth and child rearing after breast cancer. The purpose of this study was to investigate the positive and negative motivations toward childbirth of breast cancer survivors and their husbands.
Mammary stem cells and the differentiation hierarchy: current status and perspectives

Based on transplantation and lineage tracing studies, a hierarchy of stem and progenitor cells has been shown to exist among the mammary epithelium. In this review, Visvader and Stingl integrate recent data on the mammary stem cell differentiation hierarchy and its control at the transcriptional and epigenetic levels. They also discuss the relevance of the evolving hierarchy to the identification of “cells of origin” of breast cancer.