Miracle-dz/UniFAR-FTUs huggingface dataset:
Chromatin Remodeling by Rosuvastatin Normalizes TSC2-/meth Cell Phenotype through the Expression of Tuberin

Tuberous sclerosis complex (TSC) is a multi-systemic syndrome caused by mutations in TSC1 or TSC2 gene. In TSC2-null cells, Rheb, a member of the Ras family of GTPases, is constitutively activated. Statins inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase and block the synthesis of isoprenoid lipids with inhibition of Rheb farnesylation and RhoA geranylgeranylation. The effects of rosuvastatin on the function of human TSC2−/− and TSC2-/meth α-actin smooth muscle (ASM) cells have been investigated. The TSC2−/− and TSC2-/meth ASM cells, previously isolated in our laboratory from the renal angiomyolipoma of two TSC patients, do not express tuberin and bear loss of heterozigosity caused by a double hit on TSC2 and methylation of TSC2 promoter, respectively. Exposure to rosuvastatin affected TSC2-/meth ASM cell growth and promoted tuberin expression by acting as a demethylating agent. This occurred without changes in interleukin release. Rosuvastatin also reduced RhoA activation in TSC2-/meth ASM cells, and it required coadministration with the specific mTOR (mammalian target of rapamycin) inhibitor rapamycin to be effective in TSC2−/− ASM cells. Rapamycin enhanced rosuvastatin effect in inhibiting cell proliferation in TSC2−/− and TSC2-/meth ASM cells. Rosuvastatin alone did not alter phosphorylation of S6 and extracellular signal-regulated kinase (ERK), and at the higher concentration, rosuvastatin and rapamycin slightly decreased ERK phosphorylation. These results suggest that rosuvastatin may potentially represent a treatment adjunct to the therapy with mTOR inhibitors now in clinical development for TSC. In particular, rosuvastatin appears useful when the disease is originated by epigenetic defects.
Efficient location-aided flooding scheme initiated by receiver for MANETs

Flooding is a fundamental, critical, and indispensable operation for supporting various applications and protocols in wireless ad hoc networks. The traditional flooding scheme generates excessive redundant packet retransmissions, however, causing contention and packet collisions, and ultimately wasting precious limited bandwidth and energy. Recently, some flooding schemes have been studied to avoid those problems, but these algorithms either perform well in redundant transmissions or require that the node maintain information about neighbors more than one hop away. One of the most efficient approaches is found in the work of Liu et al., which uses only 1-hop neighbor information. The advantage of this scheme is that it achieves local optimality in terms of the number of retransmitting nodes, although it still produces many redundant transmissions. In this paper, we propose an efficient flooding protocol that minimizes flooding traffic by leveraging location information of 1-hop neighbor nodes. Our scheme is receiver-based, which means that each receiver of a flooding message determines whether it should forward the message based on the given retransmission rule. Simulation results show that our scheme is highly efficient. It is able to reduce the number of forward nodes almost to that of the lower bound but maintains a high delivery ratio.
Effects of tadalafil treatment combined with physical activity in patients with low onset hypogonadism: results from a not-randomized single arm phase 2 study

Abstract Purpose: To investigate a possible relation between penile Doppler ultrasound examination (PDUE) parameters and efficacy of chronic therapy with tadalafil (TAD) combined with a protocol of aerobic physical activity (PA) in patients with late onset hypogonadism (LOH). Methods: The study evaluated 30 patients consecutively enrolled with LOH and erectile dysfunction which present contraindication to hormonal replacement therapy for concomitant prostate disease. These patients were subjected to a combined protocol with phosphodiesterase V selective inhibitors (TAD 5 mg daily) and aerobic PA. Results: After three months, we observed significant improvements in erectile function [IIEF-5, median (IQR) = 13.0 (7.0–18.0) versus 6.0 (5.0–6.75); p < 0.01] and of the main metabolic [homeostatic model assessment index, median (IQR) = 2.5 (1.62–3.37) versus 3.0 (2.0–3.75); p < 0.01; body mass index, median (IQR) = 27.0 (24.0–28.75) versus 27.5 (24.0–29.5)] and vascular parameters [peak systolic velocity, median (IQR) = 29.5 (24.25–31.0) versus 28.0 (23.0–24.25); acceleration time, median (IQR) = 114 (105.25–134.0) versus 115.0 (106.5–134.0)], assessed by PDUE. Conclusion: PA in association with phosphodiesterase V inhibitors could compensate the effects of hypogonadism on erectile function and facilitate the clinical response to these drugs even in the absence of adequate serum concentrations of total testosterone.
Characteristics of smoking used cigarettes among an incarcerated population.

Little is known about smoking behaviors involving shared and previously used cigarettes, which we refer to as "smoking used cigarettes. " Examples include: cigarette sharing with strangers, smoking discarded cigarettes ("butts"), or remaking cigarettes from portions of discarded cigarettes. The current study focuses on the prevalence of and factors associated with smoking used cigarettes prior to incarceration among a U.S. prison population. Questionnaires were administered to 244 male and female inmates at baseline. Prevalence of smoking used cigarettes was assessed using 3 questions; 1 about sharing cigarettes with strangers, 1 about smoking a "found" cigarette, and 1 about smoking previously used cigarettes. Factors associated with those who engaged in smoking used cigarettes were then compared with those who did not engage in smoking used cigarettes. A majority of participants (61.5%) endorsed engaging in at least 1 smoking used cigarette behavior in the past prior to incarceration. Those who engaged in these behaviors were more likely to have a higher degree of nicotine dependence, to have started smoking regularly at a younger age, and to have lived in an unstable living environment prior to incarceration. Our results indicate that a history of smoking used cigarettes is common among incarcerated persons in the United States. Consistent with our hypothesis, engaging in smoking used cigarettes was found to be associated with a higher degree of nicotine dependence. (PsycINFO Database Record
Chromosomal defects and outcome in 1015 fetuses with increased nuchal translucency

In 1015 fetuses undergoing first‐trimester karyotyping because of increased nuchal translucency thickness, the incidence of chromosomal abnormalities increased with both maternal age and nuchal translucency thickness. The observed numbers of trisomies 21, 18 and 13 in fetuses with nuchal translucency thicknesses of 3 mm, 4 mm, 5 mm and ≥ 6 mm were approximately 3 times, 18 times, 28 times and 36 times higher than the respective numbers expected on the basis of maternal age. The incidences of Turner syndrome and triploidy were 9‐fold and 8‐fold higher but the incidence of other sex chromosome aneuploidies was similar to that of an unselected population of women undergoing first‐trimester fetal karyotyping for maternal age. In the chromosomally normal group, the incidence of structural defects, mainly cardiac, diaphragmatic, renal and abdominal wall, was approximately 4%, which is higher than would be expected in an unselected population. The rates of fetal loss in the groups with nuchal translucency thickness of 3 mm and 4 mm were 2% and 4%, respectively, which is similar to the 2.3% rate of fetal loss observed in a group of fetuses with normal nuchal translucency thickness undergoing chorion villus sampling. For fetal nuchal translucency thickness of ≥ 5 mm, the rate of fetal loss was 13%. Copyright © 1995 International Society of Ultrasound in Obstetrics and Gynecology
How to uniquely determine your location in a graph ? A metric dimension problem

The metric dimension problem was first introduced in 1975 by Slater [35], and independently by Harary and Melter [16] in 1976; however the problem for hypercube was studied (and solved asymptotically) much earlier in 1963 by Erdős and Rényi [10]. A set of vertices S resolves a graph G if every vertex is uniquely determined by its vector of distances to the vertices in S. The metric dimension of G is the minimum cardinality of a resolving set of G. Garey and Johnson [13], and also Khuller et al. [23], showed that determining the metric dimension of an arbitrary graph is an NP-complete problem. The problem is still NP-complete even if we consider some specific families of graphs, such as planar graphs [9] or Gabriel unit disk graphs [18]. Thus research in this area are then constrained towards: characterizing graphs with particular metric dimensions, determining metric dimensions of particular graphs, and constructing algorithm that best approximate metric dimensions. Until today, only graphs of order n with metric dimension 1, n− 3, n− 2, and n− 1 have been characterized [6, 21]. On the other hand, researchers have determined metric dimensions for many particular classes of graphs, such as trees [6, 16, 23], cycles [6], complete multipartite graphs [6, 31], grids [27], wheels [4, 5, 33], fans [5], unicyclic graphs[29], honeycombs [26], circulant graphs [30, 19], Jahangir graphs [36], and Sierṕıski graphs [22]. Recently in 2011, Bailey and Cameron [2] established relationship between the base size of automorphism group of a graph and its metric dimension. This result then motivated researchers to study metric dimensions of distance regular graphs, such as Grassman [3, 15], Johnson, Kneser [1], and bilinear form graphs [12, 14]. There are also some results of metric dimensions of graphs resulting from graph operations, for instance: Cartesian product graphs [27, 23, 5], joint product graphs [4, 5, 33], corona product graphs [37, 20], lexicographic product graphs [32], and amalgamation product graphs [34]. In the area of constructing algorithm that best approximate metric dimensions, recently researchers have utilized integer programming [8], genetic algorithm [24], variable neighborhood search based heuristic [28], and greedy constant factor approximation algorithm [17]. An natural analogue for oriented graphs was introduced by Chartrand, Raines, and Zhang much later in 2000 [7]. Since a directed path from one vertex to another needs
RhoB Is Stabilized by Transforming Growth Factor β and Antagonizes Transcriptional Activation*

Transforming growth factor β (TGF-β) is the prototype for an evolutionarily conserved superfamily of secreted factors implicated in diverse biological phenomena. The pleiotropic responses to TGF-β are initiated by a heteromeric receptor complex that binds and phosphorylates downstream effectors. Among these, the Smads have been extensively studied. However, less attention has been directed toward alternative downstream effectors and their participation in TGF-β signal transduction. We show that TGF-β promotes accumulation of the labile monomeric GTPase RhoB by antagonizing its normal proteolytic destruction, presumably via the 26 S proteasome. RhoB accumulates in its isoprenylated form. Transient overexpression of wild type RhoB but not its dominant negative mutant RhoB-N19 antagonizes TGF-β-mediated transcriptional activation. These results suggest a novel mechanism of regulation by TGF-β and implicate RhoB as a negative regulator of TGF-β signal transduction.
Obese women exhibit differences in ovarian metabolites, hormones, and gene expression compared with moderate-weight women.

CONTEXT Obese women experience longer times to conception, even if they are young and cycling regularly, which is suggestive of alterations in ovarian function during the periconceptual period. OBJECTIVE This study sought to determine whether there are alterations in the preovulatory follicular environment that are likely to influence oocyte developmental competence. DESIGN, SETTING, AND PARTICIPANTS Women attending a private infertility clinic were categorized into body mass index (BMI) groups of moderate (n = 33; BMI 20-24.9 kg/m(2)), overweight (n = 31; BMI 25-29.9 kg/m(2)), and obese (n =32; BMI >or=30 kg/m(2)). INTERVENTION For each patient, follicular fluid was recovered from single follicles at oocyte retrieval, granulosa cells were pooled from multiple follicular aspirates and cumulus cells were pooled after separation from the oocytes. MAIN OUTCOME MEASURES Follicle fluid was assayed for hormones and metabolites. Granulosa and cumulus cells were analyzed for mRNA expression of insulin signaling components (IRS-2 and Glut4), glucose-regulated genes (ChREBP, ACC, and FAS) and insulin-regulated genes (SREBP-1, CD36, and SR-BI) associated with obesity/insulin resistance. RESULTS Increasing BMI was associated with increased follicular fluid insulin (P < 0.001), lactate (P = 0.01), triglycerides (P = 0.0003), and C-reactive protein (P < 0.0001) as well as decreased SHBG (P = 0.001). IRS-2, Glut4, ChREBP, and SREBP exhibited cell-type-specific expression but were not affected by BMI. CD36 and SRBI mRNA were modestly altered in granulosa cells of obese compared with moderate-weight women. CONCLUSIONS Obese women exhibit an altered ovarian follicular environment, particularly increased metabolite, C-reactive protein, and androgen activity levels, which may be associated with poorer reproductive outcomes typically observed in these patients.
Cytostatic Activity of Paclitaxel in Coronary Artery Smooth Muscle Cells is Mediated Through Transient Mitotic Arrest Followed by Permanent Post-Mitotic Arrest: Comparison with Cancer Cells

The anti-cancer agent paclitaxel (PTX) is an effective anti-restenosis agent on drug eluting stents, primarily due to growth inhibition of coronary artery smooth muscle cells (CASMC) across a wide dose range. In this study, we compared the effects of PTX on CASMC to apoptotic-prone HL60 leukemia cells and apoptotic-reluctant A549 lung cancer cells to assess cell survival mechanisms. In comparison to HL60 and A549 cells, CASMC had a shorter mitotic arrest and a lower mitotic index. While CASMC and A549 cells did not become apoptotic and displayed a multi-nucleated phenotype, HL60 cells showed prolonged mitotic arrest followed by apoptosis. CASMC exiting mitosis were arrested in G1 as MN tetraploid cells, with decreased levels of cyclin B1 and PCNA. CASMC remained metabolically active, becoming permanently arrested as evidenced by increased levels of β-galactosidase activity. These cells did not demonstrate elevated levels of inflammatory markers. Our findings suggest that a weak mitotic checkpoint or inhibited apoptotic cascade, or a combination of both, determine cell survival following PTX treatment. These in vitro findings suggest a mechanism for the cytostatic activity of PTX in CASMC for the inhibition of restenosis.
Early signs of longitudinal progressive cone photoreceptor degeneration in achromatopsia

Aims To characterise longitudinal progressive retinal changes in achromatopsia. Methods Ultrahigh-resolution spectral optical coherence tomography (Copernicus, 3 μm axial resolution) was used to obtain tomograms of the fovea from five children and three adults with achromatopsia. Each patient was scanned twice with a mean follow-up time of 16 months. Progressive changes in reflectivity at the inner segment/outer segment (IS/OS) junction, the central macular and outer nuclear layer thickness were analysed. Results Younger patients (<10 years; patient 1–5) showed progressive morphological changes at the IS/OS junction between visits 1 and 2. However, older patients (>40 years; patients 6–8) did not have any changes in the retinal morphology between visits 1 and 2. In patients 1 and 2, IS/OS discontinuities (visit 1) developed into a hyper-reflective zone confined to the fovea (visit 2). In patient 3, the hyper-reflective zone (visit 1) progressed to form an IS/OS disruption and early formation of a small hypo-reflective zone (visit 2). Patients 4 and 5 had a hypo-reflective zone (visit 1) which subsequently increased in size (visit 2). There was a decrease in central macular and outer nuclear layer thickness between visits 1 and 2 in children. Conclusions For the first time, we show progressive longitudinal changes in retinal morphology in achromatopsia. Early changes include subtle IS/OS reflectivity alterations. The dynamic retinal changes in younger patients provide evidence that it represents a progressive disorder, and implementation of gene therapy during the early stages of the disease may provide best prognosis.
Predicting Factors of Depression, Antidepressant Use and Positive Response to Antidepressants in Perinatal and Postpartum Women

Background: In the United States, there is a disparity in knowledge of nationwide depression prevalence, the antidepressant use and the antidepressant responses during perinatal/postpartum periods. Objective: This study investigated the predicting factors of depression, antidepressant use and positive antidepressant response during the perinatal/postpartum periods. Method: The 2007-2012 National Health and Nutrition Examination Surveys (NHANES) were combined to identify adult pregnant women, those within the 18-month postpartum period (n=492) and their depression statuses via demographics, health care accessibility, antidepressant use and illicit drug use information. The characteristics of different study groups were compared (depression versus no-depression groups, antidepressant users versus non-antidepressant users, and antidepressant responders versus antidepressant non-responders). Multivariable logistic regression analysis was used to predict factors of perinatal depression (PND)/ postpartum depression (PPD), antidepressant use and antidepressant positive response in PND/PPD. Results: PND/PPD individuals had higher rates of mental health visits. No predicting factor for developing PND/PPD was shown. Antidepressant users were significantly older with insurance and recent health checkups/ mental visits. Being below the poverty level and having some health care accessibility are predictors for being on antidepressants. Recent non-illicit drug use is a predictor for PND/PPD symptom improvement while on antidepressants. Conclusion: The group of those with social-economic disadvantages was more likely to be on antidepressants for PND/PPD. Illicit drug users were less likely to show improvement with antidepressants. The safety and efficacy of antidepressant use during this period is controversial. More studies need to focus on the barriers involving antidepressant treatments, the safety and outcomes of antidepressants for PND/PPD management.
Curriculum Implementation and Reform: Teachers' Views about Kuwait's New Science Curriculum.

The MoE (Ministry of Education) in the state of Kuwait is starting to reform the science curriculum in all school academic stages: primary (1−5) grades, intermediate (6−9) grades, and secondary (10−12) grades. The purpose of this study was to explore the opinions of science teachers about Kuwait’s new sixth and seventh grade science curriculum, which was implemented in 2008. This study focused on the teachers’ views regarding curriculum content and revealed the challenges and difficulties they face in teaching this new curriculum. Data were collected from 136 teachers’ questionnaires and four interviews. The findings indicated that the curriculum content did not help students work together and was not related to the students’ culture and society. The findings also showed that science teachers faced many challenges in teaching the new curriculum, like a lack of teaching tools in the schools and the fact that the MoE did not provide any course training related to the new curriculum. To conclude, the findings suggest that the new curriculum should be reviewed and modified with the teachers’ involvement.
Effect of an occupation-based cultural heritage intervention in long-term geriatric care: a two-group control study.

OBJECTIVE We investigated the effectiveness of an occupation-based cultural heritage intervention to facilitate adaptation to relocation into long-term care (LTC) facilities as measured by quality of life, activity engagement, and social participation. METHOD We used a quasi-experimental nonequivalent control group design with pre- and posttests. Residents receiving the cultural intervention were compared with residents in a typical activity group. Eight sessions, two per week for 4 wk, were facilitated by certified occupational therapy assistants. RESULTS Twenty-nine participants completed the group sessions. Quality-of-life scores improved significantly over time for both groups. Statistically, a greater percentage of time was spent in discretionary than obligatory time, pretest and posttest, with no significant difference between groups. CONCLUSION The study demonstrated effectiveness of a structured, occupation-based social group intervention that improved quality of life, an indicator of adaptation. It also provided a description of activity patterns and social participation of LTC residents.
Continuous Femoral Versus Posterior Lumbar Plexus Nerve Blocks for Analgesia After Hip Arthroplasty: A Randomized, Controlled Study

BACKGROUND:Hip arthroplasty frequently requires potent postoperative analgesia, often provided with an epidural or posterior lumbar plexus local anesthetic infusion. However, American Society of Regional Anesthesia guidelines now recommend against epidural and continuous posterior lumbar plexus blocks during administration of various perioperative anticoagulants often administered after hip arthroplasty. A continuous femoral nerve block is a possible analgesic alternative, but whether it provides comparable analgesia to a continuous posterior lumbar plexus block after hip arthroplasty remains unclear. We therefore tested the hypothesis that differing the catheter insertion site (femoral versus posterior lumbar plexus) after hip arthroplasty has no impact on postoperative analgesia. METHODS:Preoperatively, subjects undergoing hip arthroplasty were randomly assigned to receive either a femoral or a posterior lumbar plexus stimulating catheter inserted 5 to 15 cm or 0 to 1 cm past the needle tip, respectively. Postoperatively, patients received perineural ropivacaine, 0.2% (basal 6 mL/hr, bolus 4 mL, 30-minute lockout) for at least 2 days. The primary end point was the average daily pain scores as measured with a numeric rating scale (0–10) recorded in the 24-hour period beginning at 07:30 the morning after surgery, excluding twice-daily physical therapy sessions. Secondary end points included pain during physical therapy, ambulatory distance, and supplemental analgesic requirements during the same 24-hour period, as well as satisfaction with analgesia during hospitalization. RESULTS:The mean (SD) pain scores for subjects receiving a femoral infusion (n = 25) were 3.6 (1.8) versus 3.5 (1.8) for patients receiving a posterior lumbar plexus infusion (n = 22), resulting in a group difference of 0.1 (95% confidence interval −0.9 to 1.2; P = 0.78). Because the confidence interval was within a prespecified −1.6 to 1.6 range, we conclude that the effect of the 2 analgesic techniques on postoperative pain was equivalent. Similarly, we detected no differences between the 2 treatments with respect to the secondary end points, with one exception: subjects with a femoral catheter ambulated a median (10th–90th percentiles) 2 (0–17) m the morning after surgery, in comparison with 11 (0–31) m for subjects with a posterior lumbar plexus catheter (data nonparametric; P = 0.02). CONCLUSIONS:After hip arthroplasty, a continuous femoral nerve block is an acceptable analgesic alternative to a continuous posterior lumbar plexus block when using a stimulating perineural catheter. However, early ambulatory ability suffers with a femoral infusion.