Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of Bile Acid Sequestrants on the Risk of Cardiovascular Events: A Mendelian Randomization Analysis

Background—Statins lower low-density lipoprotein cholesterol (LDL-C) and risk of coronary artery disease (CAD), but they may be ineffective or not tolerated. Bile acid sequestrants (BAS) reduce LDL-C, yet their clinical efficacy on CAD remains controversial. Methods and Results—We conducted a systematic review and meta-analysis of randomized controlled trials to assess the effect of cholestyramine and colesevelam. We then used Mendelian randomization to estimate the effect of BAS on reducing the risk of CAD. First, we quantified the effect of rs4299376 (ABCG5/ABCG8), which affects the intestinal cholesterol absorption pathway targeted by BAS and then we used these estimates to predict the effect of BAS on CAD. Nineteen randomized controlled trials with a total of 7021 study participants were included. Cholestyramine 24 g/d was associated with a reduction in LDL-C of 23.5 mg/dL (95% confidence interval [CI] −26.8,−20.2; N=3806) and a trend toward reduced risk of CAD (odds ratio 0.81, 95% CI 0.70–1.02; P=0.07; N=3806), whereas colesevelam 3.75 g/d was associated with a reduction in LDL-C of 22.7 mg/dL (95% CI −28.3, −17.2; N=759). Based on the findings that rs4299376 was associated with a 2.75 mg/dL decrease in LDL-C and a 5% decrease in risk of CAD outcomes, we estimated that cholestyramine was associated with an odds ratio for CAD of 0.63 (95% CI 0.52–0.77; P=6.3×10−6) and colesevelam with an odds ratio of 0.64 (95% CI 0.52–0.79, P=4.3×10−5), which were not statistically different from BAS clinical trials (P>0.05). Conclusions—The cholesterol lowering effect of BAS may translate into a clinically relevant reduction in CAD.
IVF and endometriosis-related symptom progression: insights from a prospective study.

BACKGROUND A possible and neglected concern in women with endometriosis undergoing IVF is the potential risk of progression of the disease. We set up a prospective study mainly aimed at evaluating the impact of IVF on endometriosis-related symptoms. MATERIALS AND METHODS Women with surgical or echographic diagnosis of endometriosis and selected for IVF were included. In the month preceding the IVF attempt and at a second evaluation 3-6 months after the cycle, women who did not get pregnant underwent clinical assessment and transvaginal ultrasonography. Each patient was requested to complete a questionnaire on the presence, severity and modifications of endometriosis-related symptoms before and after the IVF cycle. RESULTS Overall, 64 patients completed the study protocol. The Biberoglu-Behrman Scores and the Verbal Rate Scales for dysmenorrhea, dispareunia and chronic pelvic pain did not worsen after the procedure. Other endometriosis-related symptoms also did not change. There was no modification in size and number of endometriomas and deep peritoneal nodules. The number (%) of women reporting general improvement and worsening were 14 (22%) and 7 (11%), respectively. CONCLUSIONS IVF does not expose women to a consistent risk of endometriosis-related symptoms progression.
Misattribution of Reference Dependence : Evidence from Real-Effort Experiments

A growing body of evidence suggests that utility is reference dependent and outcomes are compared against recent expectations. When learning from experience, errors may arise if people neglect the degree to which their experienced utility was shaped by their expectations. In this paper, we use a pair of experiments to examine whether biased beliefs arise from a failure to retrospectively account for sensations of positive and negative surprise. Participants learn from experience about one of two unfamiliar tasks, one more onerous than the other. Some participants were assigned their task by chance just prior to working, while others knew in advance which task they would face. In a second session conducted hours later, we elicit participants’ willingness to work at that same task. Relative to participants who knew with certainty which task they would face, participants assigned to the less-onerous task by chance were more willing to work, while participants assigned to the more-onerous task by chance were less willing to work. These qualitative results, and the fact that differences in willingness to work remained hours after initial impressions were formed, are consistent with the idea that participants mistakenly attributed sensations of positive or negative surprise to the effort cost of their assigned task. JEL Classification: C91, D03.
A Nucleocapsid Functionality Contained within the Amino Terminus of the Ty1 Protease That Is Distinct and Separable from Proteolytic Activity

ABSTRACT Ty1 is the most successful of the five endogenous yeast retrotransposons. The life cycle of Ty1 dictates that a number of nucleocapsid (NC)-facilitated events occur although the protein(s) responsible for these events has not been identified. The positioning of the NC peptide is conserved at the carboxy terminus of the Gag protein among most long terminal repeat (LTR)-containing retroelements. An analogous region of Ty1 that simultaneously encodes part of Gag, protease (PR), and the C-terminal p4 peptide was mutagenized. Some of these mutations result in smaller-than-normal virus-like particles (VLPs). The mutants were also found to impair an NC-like functionality contained within the amino terminus of the protease that is distinct and separable from its proteolytic activity. Remarkably, these mutants have distinct defects in reverse transcription.
Disimpaction of children with severe constipation in 3–4 days in a suburban clinic using polyethylene glycol with electrolytes and sodium picosulphate

Constipation is a common cause of admission to hospital for disimpaction, as oral laxatives are often inadequate. High‐dose oral laxative protocols are used for complete bowel clearance prior to colonoscopy, but have not been reported for treating faecal impaction. The aim of this study was to assess the effectiveness of a high‐dose oral protocol using polyethylene glycol with electrolytes (PEG + E) (Movicol Rx) combined with sodium picosulphate (SP) (Dulcolax SP Rx) in faecal impaction in children presenting to a suburban clinic.
Antagonism of RANTES Receptors Reduces Atherosclerotic Plaque Formation in Mice

Abstract— Increasing evidence supports the involvement of inflammation in the early phases of atherogenesis. Recruitment of leukocytes within the vascular wall, controlled by chemokines, is an essential process in the development of this common disease. In this study, we report that blocking a chemokine pathway in vivo with the CC chemokine antagonist Met-RANTES reduces the progression of atherosclerosis in a hypercholesterolemic mouse model. The reduction of lesions was correlated with a diminution of expression of several major chemokines and chemokine receptors, a decrease in leukocyte infiltration, and an increase of collagen-rich atheroma, features associated with stable atheroma. Treatment was well tolerated and serum lipid profiles were not affected. Whereas genetically engineered mice with deletion of either a CC chemokine or its receptor have demonstrated resistance to disease, to our knowledge, this is the first demonstration that treatment with a chemokine receptor antagonist limits the progression of atherosclerosis in vivo. Thus, our findings indicate that blockade of chemokine receptor/ligand interactions might become a novel therapeutic strategy to reduce the evolution of this common disease.
Yeast Reporter Assay to Identify Cellular Components of Ricin Toxin A Chain Trafficking

RTA, the catalytic A-subunit of the ribosome inactivating A/B toxin ricin, inhibits eukaryotic protein biosynthesis by depurination of 28S rRNA. Although cell surface binding of ricin holotoxin is mainly mediated through its B-subunit (RTB), sole application of RTA is also toxic, albeit to a significantly lower extent, suggesting alternative pathways for toxin uptake and transport. Since ricin toxin trafficking in mammalian cells is still not fully understood, we developed a GFP-based reporter assay in yeast that allows rapid identification of cellular components required for RTA uptake and subsequent transport through a target cell. We hereby show that Ypt6p, Sft2p and GARP-complex components play an important role in RTA transport, while neither the retromer complex nor COPIB vesicles are part of the transport machinery. Analyses of yeast knock-out mutants with chromosomal deletion in genes whose products regulate ADP-ribosylation factor GTPases (Arf-GTPases) and/or retrograde Golgi-to-ER (endoplasmic reticulum) transport identified Sso1p, Snc1p, Rer1p, Sec22p, Erv46p, Gea1p and Glo3p as novel components in RTA transport, suggesting the developed reporter assay as a powerful tool to dissect the multistep processes of host cell intoxication in yeast.
Evaluating stereo vision and user tracking in mixed reality tasks!

Advances in head tracking and stereoscopic visualization technologies have fostered the implementation of subjective display systems able to render a 3D scene perspective-corrected according to the position of the user. This enables a whole class of mixed reality applications and interaction paradigms, where the user is able to move freely around the scene and to perform tasks involving the interplay between physical and virtual objects. The accuracy and ergonomics of such tasks strongly depend on the ability of the subjective display system to offer not only a convincing 3D visual experience, but also, and mostly, an accurate rendering of the virtual scene in terms of spatial and metric relations between virtual and physical scene components. In this paper we study the role and impact of head tracking and stereo visualization in mixed reality contexts using a set of measuring tasks involving physical rulers and virtual objects, performed under different rendering conditions. Specifically, we analyze to what extent the two features contribute to give the user the correct alignment between the virtual and the real components of a 3D scene. Finally, we draw some conclusions about their impact within different scenarios.
Sarcoidosis in Ireland: regional differences in prevalence and mortality from 1996-2005.

BACKGROUND Sarcoidosis is a common multisystem disease of unknown cause and Ireland is among the countries with the highest reported prevalence of disease worldwide. Despite this, reports on the geographical distribution of disease and differences in mortality due to sarcoidosis within Northern Ireland (NI) and the Republic of Ireland (ROI) are currently lacking. OBJECTIVE This study was performed to examine sarcoidosis prevalence and mortality in Ireland (NI and ROI) to specifically determine if geographical or temporal clusters of disease are present and if any differences in mortality exist between NI and ROI. DESIGN A retrospective study, examining hospital discharge data for NI and ROI and data on deaths due to sarcoidosis, obtained from the relevant official government agencies. RESULTS For 1996-2005, the prevalence of sarcoidosis was 28.13 per 100,000 for ROI compared with 11.16 per 100,000 for NI (p = 0.002). Two significant spatial clusters of disease were detected in the Northwest (Prevalence = 44.9 per 100,000) and also the Midlands region (32.1 per 100,000). Two lower-prevalence spatial clusters were also detected in the South and Southeast of ROI. Temporal clustering was also present throughout ROI and NI for the years 2000 to 2004, while space-time clustering was found in three regions, the West (ROI), the East (ROI) and Northeast (ROI and NI). The case fatality rate for ROI was 0.84%, and for NI was 1.44% (p = 0.03). CONCLUSION Considerable heterogeneity in disease prevalence is evident in Ireland as significant spatial, temporal and space-time clusters of sarcoidosis are demonstrated in this study. Prevalence rates are also higher than that previously reported for Ireland and are comparable to those of Scandinavian countries. Although case-fatality is low in both ROI and NI, it is significantly lower in ROI. Further study is needed to investigate these findings and the creation of an all-island sarcoidosis registry would provide a mutually beneficial means of capturing this data more effectively.
Ventromedial prefrontal cortex and amygdala dysfunction during an anger induction positron emission tomography study in patients with major depressive disorder with anger attacks.

CONTEXT Although a variety of functional neuroimaging studies have used emotion induction paradigms to investigate the neural basis of anger in control subjects, no functional neuroimaging studies using anger induction have been conducted in patient populations. OBJECTIVE To study the neural basis of anger in unmedicated patients with major depressive disorder with anger attacks (MDD + A), unmedicated patients with MDD without anger attacks (MDD - A), and controls. DESIGN We used positron emission tomography, psychophysiologic measures, and autobiographical narrative scripts in the context of an anger induction paradigm. SETTING Academic medical center. PARTICIPANTS Thirty individuals, evenly divided among the 3 study groups. INTERVENTIONS In separate conditions, participants were exposed to anger and neutral autobiographical scripts during the positron emission tomography study. Subjective self-report and psychophysiologic data were also collected. MAIN OUTCOME MEASURES Voxelwise methods were used for analyses of regional cerebral blood flow changes for the anger vs neutral contrast within and between groups. RESULTS Controls showed significantly (P<.001) greater regional cerebral blood flow increases in the left ventromedial prefrontal cortex during anger induction than patients with MDD + A, whereas these differences were not present in other between-group analyses. Also, in controls, an inverse relationship was demonstrated between regional cerebral blood flow changes during anger induction in the left ventromedial prefrontal cortex and left amygdala, whereas in patients with MDD + A there was a positive correlation between these brain regions during anger induction. There was no significant relationship between these brain regions during anger induction in patients with MDD - A. CONCLUSION These results suggest a pathophysiology of MDD + A that is distinct from that of MDD - A and that may be responsible for the unique clinical presentation of patients with MDD + A.
Sex Differences in Health Status After Coronary Artery Bypass Surgery

Background—Although previous studies have shown functional improvements in patients who undergo coronary artery bypass graft (CABG) surgery, data are conflicting on whether the gains achieved by women are similar to or less than those achieved by men. Methods and Results—We compared physical and psychological functional gains and readmission rates between 777 men and 295 women who underwent first CABG consecutively between February 1999 and February 2001. Physical function and mental health were measured by means of the Short Form 36-Item Health Survey (SF-36). At 6 months, both men and women showed, on average, a significant improvement in physical function and mental health, but men improved significantly more than women. After adjustment for baseline characteristics, the mean score improvement in women was half that of men for physical function (7.3 versus 14.0, P =0.0002) and 25% less than that of men for mental health (−3.0 versus 8.9, P =0.026). The absolute rates of adverse outcomes, such as hospital readmission, worsening functional status, and worsening mental health, were significantly higher in women (32.6%, 25.7%, and 17.5%, respectively) than in men (21.2%, 11.1%, and 12.6%, respectively) and remained significantly different in multivariable analysis. Conclusions—CABG surgery is associated with lower functional gains and higher readmission rates in women compared with men 6 months after operation.
Screening for stroke in sickle cell anemia: comparison of transcranial Doppler imaging and nonimaging US techniques.

PURPOSE To determine whether criteria for screening patients with sickle cell anemia for stroke established with a nonimaging transcranial Doppler ultrasonographic (US) technique are applicable to studies performed with a transcranial Doppler US imaging technique. MATERIALS AND METHODS One hundred sixty-eight examinations in 66 children were performed for sickle cell stroke screening. Children were examined with nonimaging and imaging transcranial Doppler US techniques on the same day, for a total of 84 paired examinations. The time-averaged maximum mean velocity (V(mean)) and resistive index (RI) were calculated in the middle cerebral arteries, bifurcations of the distal internal carotid arteries, distal internal carotid arteries, anterior cerebral arteries, posterior cerebral arteries, and basilar arteries. The maximum systolic velocity (V(max)) was evaluated in the distal internal carotid arteries and middle cerebral arteries. V(mean), V(max), and RI measurements were subjected to repeated-measures multivariate analysis of covariance, and the Pearson product moment correlation was used for middle cerebral artery velocity, age, and hemoglobin. RESULTS V(mean) measurements obtained with nonimaging and imaging techniques varied substantially for the bifurcation of the distal internal carotid artery, the posterior cerebral artery, and the basilar artery. Substantial differences were found in RIs for every vessel. Examination time was shorter with the nonimaging technique. CONCLUSION V(mean) measurements in the middle cerebral artery, distal internal carotid artery, and anterior cerebral artery did not vary substantially between nonimaging and imaging transcranial Doppler US. RI data did not yield comparable measurements.
Different measures, different outcomes? Survey into the effectiveness of chronic pain clinics in a London tertiary referral center

Background Chronic pain clinics aim to improve challenging conditions, and although numerous studies have evaluated specific aspects of therapies and outcomes in this context, data concerning service impact on outcome measures in a general pain population are sparse. In addition, current trends in commissioning increasingly warrant services to provide evidence for their effectiveness. While a plethora of outcome measures, such as pain-intensity or improvement scores, exist for this purpose, it remains surprisingly unclear which one to use. It also remains uncertain what variables predict treatment success. Objectives This cross-sectional study was conducted to evaluate clinic performance employing different tools (pain scores, pain categories, responder analysis, subjective improvement, satisfaction), and to determine predictors of outcome measures. Patients and methods Patients attending scheduled clinic follow-up appointments were approached. They were asked to complete the modified short-form Brief Pain Inventory (BPI-SF) that also included assessments for satisfaction and subjective improvement. Comparisons were made with BPI-SF responses that were completed by each patient on admission. Nonparametric tests were employed to evaluate service impact and to determine predictors for outcome. Results Data of 118 patients were analyzed. There was considerable variation in impact of pain clinics depending on the outcome measure employed. While median pain scores did not differ between admission and follow-up, scores improved individually in 30% of cases, such that more patients had mild pain on follow-up than on admission (relative risk 2.7). Furthermore, while only 41% reported at least moderate subjective improvement after admission to the service, the majority (83%) were satisfied with the service. Positive treatment responses were predicted by “number of painful regions” and “changes in mood”, whereas subjective improvement was predicted by “helpfulness of treatments”. Conclusion Depending on the outcome measure employed, pain clinics showed varying degrees of impact on patients’ pain experiences. This calls into question the current practice of using nonstandardized outcome reporting for evaluation of service performances.
Effects of dietary supplementation of Acanthopanax senticosus on gastrointestinal tract development in calves.

Twenty-four newborn Holstein dairy male calves (with initial body weight of 38 ± 3.0 kg) were used in a randomized block design experiment to determine effects of dietary supplementation of Acanthopanax senticosus (AS) on gastrointestinal tract development. Calves were fed milk (10%/body weight) three times at 06.00, 12.00 and 18.00 hours daily with one to four treatments during the experimental periods (4 to 28 days): no supplementation of AS (control group, CG); 1.0 g/L•time of micro-powder AS (MP); 1.0 g/L•time of superfine powder AS (SP); or 1.0 g/L•time of coarse powder AS (CP). On days 7, 14, 21 and 28, 20 mL blood samples were collected at 06.00 hours before the morning feeding. At the end of the trial (28 days), all calves were euthanized, and tissue samples were taken and placed in 4% buffered formaldehyde for analyses. In the rumen of MP treatment, compared with the CG treatment, wall thickness and papillae diameter was both significantly lower (P<0.05), while crypt depth was significantly greater (P<0.05). In the duodenum, villi diameter of AS supplemented treatments was significantly lower than that of CG treatment (P<0.05). Results indicate that calves during sucking period supplemented with AS as MP style could promote gastrointestinal development.
The Stemness Phenotype Model

The identification of a fraction of cancer stem cells (CSCs) associated with resistance to chemotherapy in most solid tumors leads to the dogma that eliminating this fraction will cure cancer. Experimental data has challenged this simplistic and optimistic model. Opposite to the classical cancer stem cell model, we introduced the stemness phenotype model (SPM), which proposed that all glioma cells possess stem cell properties and that the stemness is modulated by the microenvironment. A key prediction of the SPM is that to cure gliomas all gliomas cells (CSCs and non-CSCs) should be eliminated at once. Other theories closely resembling the SPM and its predictions have recently been proposed, suggesting that the SPM may be a useful model for other type of tumors. Here, we review data from other tumors that strongly support the concepts of the SPM applied to gliomas. We include data related to: (1) the presence of a rare but constant fraction of CSCs in established cancer cell lines, (2) the clonal origin of cancer, (3) the symmetrical division, (4) the ability of “non-CSCs” to generate “CSCs,” and (5) the effect of the microenvironment on cancer stemness. The aforenamed issues that decisively supported the SPM proposed for gliomas can also be applied to breast, lung, prostate cancer, and melanoma and perhaps other tumors in general. If the glioma SPM is correct and can be extrapolated to other types of cancer, it will have profound implications in the development of novel modalities for cancer treatment.
An Entropy Inequality for Symmetric Random Variables

We establish a lower bound on the entropy of weighted sums of (possibly dependent) random variables (X<inf>1</inf>, X<inf>2</inf>, …, X n) possessing a symmetric joint distribution. Our lower bound is in terms of the joint entropy of (X<inf>1</inf>, X<inf>2</inf>, …, Xn). We show that for <tex>$n$</tex> ≥ 3, the lower bound is tight if and only if X<inf>i</inf>'S are i.i. d. Gaussian random variables. For <tex>$n$</tex> = 2 there are numerous other cases of equality apart from i.i. d. Gaussians, which we completely characterize. Going beyond sums, we also present an inequality for certain linear transformations of (X<inf>1</inf>, …, X n.). Our primary technical contribution lies in the analysis of the equality cases, and our approach relies on the geometry and the symmetry of the problem.