Miracle-dz/UniFAR-FTUs huggingface dataset:
The influence of 13-cis retinoic acid on human meibomian gland epithelial cells.

PURPOSE Meibomian gland dysfunction (MGD) is a primary cause of dry eye disease. One of the risk factors for MGD is exposure to 13-cis retinoic acid (13-cis RA), a metabolite of vitamin A. However, the mechanism is not well understood. We hypothesize that 13-cis RA inhibits cell proliferation, promotes cell death, alters gene and protein expressions, and attenuates cell survival pathways in human meibomian gland epithelial cells. METHODS To test our hypotheses, immortalized human meibomian gland epithelial cells were cultured with or without 13-cis RA for varying doses and time. Cell proliferation, cell death, gene expression, and proteins involved in proliferation/survival and inflammation were evaluated. RESULTS We found that 13-cis RA inhibited cell proliferation, induced cell death, and significantly altered the expression of 6726 genes, including those involved in cell proliferation, cell death, differentiation, keratinization, and inflammation, in human meibomian gland epithelial cells. Further, 13-cis RA also reduced the phosphorylation of Akt and increased the generation of interleukin-1β and matrix metallopeptidase 9. CONCLUSIONS Exposure to 13-cis RA inhibits cell proliferation, increases cell death, alters gene expression, changes signaling pathways, and promotes inflammatory mediator and protease expression in meibomian gland epithelial cells. These effects may be responsible, at least in part, for the 13-cis RA-related induction of MGD.
The Association between Socio-economic Context at Individual and Neighbourhood Levels, Wellbeing and Lifestyle Behaviours of Young Iranian Women

Background: This study explored the relationship between socio-economic characteristics at the individual and neighbourhood levels, and wellbeing and lifestyle behaviours of young Iranian women. Methods: Cluster convenience sampling was used to select 391 Iranian women participated in this cross-sectional survey in Shiraz, Iran in 2013. A scale adapted from the British General Household Social Capital questionnaire was used to assess neighbourhood socio-economic characteristics. The satisfaction with life scale, WHO quality of life scale, and the International Health and Behaviours Survey were used to measure wellbeing outcomes and lifestyle behaviours. Results: Findings showed participants were dissatisfied with their neighbourhood socio-economic conditions (M: 36.3±9.8, score range: 11–60) as well as the availability of leisure facilities (M: 1.8, score range: 1–5) in their local areas. Correlations and regression analysis revealed that better neighbourhood socio-economic characteristics were positively associated with better wellbeing outcomes as well as healthier lifestyle behaviours. Conclusion: These findings suggest the need for transitioning economies to be cognisant of the importance of social policy and strategies for enhancing neighbourhood socioeconomic status in order to enhance wellbeing outcomes for sub-populations, including young women.
Preliminary Evaluation of the AxSYM B-Type Natriuretic Peptide (BNP) Assay and Comparison with the ADVIA Centaur BNP Assay

and fluorescence de-rivatisation with isonicotinic acid hydrazide. Chromatographia 2000;52:810 – 4. 15. Murphy BEP. Clinical evaluation of urinary cor-tisol determinations by competitive protein-binding radioassay. Some studies of the protein-binding of steroids and their application to the routine micro and ultramicro measurement of various steroids in body fluids by competitive protein-binding radioassay. Determination of cortisol in guinea pig urine by high performance thin-layer chromatography , high performance liquid chromatography , and thin-layer chromatography/radio-immunoassay. Preliminary Evaluation of the AxSYM B-Type Natriuretic Peptide (BNP) Assay and Comparison with the ADVIA Centaur BNP Assay To the Editor: Blood measurements of B-type natri-uretic peptide (BNP), a cardiac neu-rohormone, are proposed as a diagnostic and prognostic aid in congestive heart failure (CHF) and as a prognostic marker in acute coronary syndromes (ACS) (1). In addition , there are preliminary data indicating a possible role of BNP as an aid in guiding medical therapy in patients with CHF (2, 3). The growing interest in clinical determination of BNP has led to the development of immunoassays for the determination of this analyte that are suitable for fully automated, high-throughput clinical instruments with random access , e.g., the ADVIA Centaur BNP (Bayer Diagnostics) and AxSYM BNP (Abbott Laboratories). We aimed to perform a preliminary analytical evaluation of the recently developed AxSYM BNP assay and to compare its clinical performance with that of the ADVIA Centaur BNP assay. The properties of the ADVIA Centaur BNP assay have been reported previously (4). As indicated by the manufacturer, the AxSYM BNP assay, produced by Axis-Shield plc for Abbott Laboratories , is a fully automated micropar-ticle enzyme immunoassay that uses two monoclonal mouse antibodies in a two-step sandwich format. The analyte is captured on anti-BNP-coated latex microparticles with detection via alkaline phosphatase and measurement of fluorescence produced from the breakdown of 4-methylumbelliferyl phosphate sub-strate. The solid-phase antibody is directed at the NH 2 terminus of the BNP peptide, whereas the conjugate antibody is directed at the COOH terminus. Six calibrators are used for the AxSYM BNP assay. Calibrator A is an acetate buffer with protein stabilizers. Calibrators B–F contain increasing concentrations of synthetic BNP (100, 400, 1000, 2000, and 4000 ng/L) in acetate buffer with protein stabilizers. These calibrators are traceable to a reference standard that was prepared gravimetrically with synthetic BNP; the reference standard underwent a value assignment to align with the Biosite Triage BNP assay with a decision threshold of 100 …
Farnesyltransferase inhibitors-induced autophagy: Alternative mechanisms?

Farnesyltransferase inhibitors (FTIs) were designed to block the action of Ras oncoproteins which depend on posttranslational modification by adding a farnesyl isoprenoid membrane anchor. However, off-target actions are believed to account for most of their antitumor activity. We recently reported the induction of autophagy in cancer cells in a dose-dependent manner by FTIs. We observed similar results of autophagy in a panel of tumor cell lines for the three FTIs tested. Therefore, the induction of autophagy is very likely a pharmacological class effect of inhibition of farnesyltransferase. In this addendum, we discuss the possible mechanisms underlying the induction of autophagy by FTIs, including reactive oxygen species-, DNA damage- and Ras-mediated pathways as alternatives to Rheb-mediated regulation of mTOR and autophagy.
Adding definition to active probing

Active probing techniques have overwhelmingly been based on a few key heuristics. To progress to the next level a more powerful approach is needed, which is capable of filtering noise effectively, designing (and defining) optimal probing strategies, and understanding fundamental limitations. We provide a probabilistic, queueing-theoretic treatment that contributes to this program in the single hop case. We provide an exact inversion method for cross traffic distributions, rigorous system identifiability results to help determine what active probing can and canâ t achieve, a new approach for treating queueing theoretic â noiseâ based on conditioning, and cross traffic estimators with enhanced properties
Ontogenesis of the Reticulum with Special Reference to Neuroendocrine and Glial Cells: A Comparative Analysis of the Merino Sheep and Iberian Red Deer

The present study was designed to compare the differences in the ontogenesis of the reticulum in sheep (domestic ruminant) and deer (wild ruminant). A total of 50 embryos and foetuses Merino sheep and 50 Iberian deer were used, from the first pre‐natal life until birth. The appearance of the reticulum from the primitive gastric tube was earlier in the sheep (22% gestation, 33 days) than in the deer (25% gestation, 66 days). In both cases, it displayed a primitive epithelium of a stratified, cylindrical, non‐ciliary type. At around 48% gestation in the sheep (72 days) and 36% (97 days) in the deer, the reticulum was configured of four clearly differentiated layers: mucosa (with epithelial layer and lamina propria), submucosa, tunica muscularis and serosa. The stratification of the epithelial layer was accompanied by modifications in its structure with the appearance of the primitive reticular ribs. The primary ribs began to be formed first in the deer, at 117 days of pre‐natal life (40% gestation) and later in the sheep (79 days, 53% gestation). The differentiation of the corneum papillae in the primary ribs coincided with the appearance of secondary reticular ribs. These structures began to be formed first in the deer, at 142 days of pre‐natal life (51% gestation) and later in the sheep (83 days, 55% gestation). The presence of neuroendocrine cells (non‐neuronal enolase‐positive cells) in the reticular mucosa was not detected until 97 days (36% gestation) in deer and 81 days (54% gestation) in sheep. The presence of glial cells (GFAP‐positive cells) occurred at around 142 days (51% gestation) in deer and at 112 days (75% gestation) in sheep. In conclusion, the presence of neuroendocrine and glial cells was detected in deer at earlier stages than sheep.
Rehabilitation following total hip arthroplasty evaluation over short follow-up time: randomized clinical trial.

UNLABELLED Hip osteoarthritis (OA) is a degenerative disease, and total hip arthroplasty (THA) is one of the surgical procedures of choice to improve the OA patient's quality of life. Without a rehabilitation program, THA patients will develop functional limitations. A randomized double-blind trial was performed between July 2009 and October 2011 to compare in a short follow-up time two groups of patients who underwent THA for OA. The THA protocol (THAP) group received verbal instructions and physiotherapy exercise demonstrations, and the THA physiotherapy care protocol (THAPCP) group received the same verbal instructions and demonstrations associated with daily exercise practice guided by a physiotherapist. The outcomes that were assessed preoperatively and 15 d postoperatively in 106 patients were muscle strength force, goniometry, Medical Outcomes Study 36-Item Short Form Health Survey, and Merle d'Aubigné and Postel score. Higher muscle strength force scores and degrees in range of motion were found in the THAPCP group. Higher improvements were also observed for the THAPCP group compared with the THAP group in the Merle d'Aubigné and Postel score. At the end of the follow-up period, the intervention in the THAPCP group improved functional capacity, quality of life, mobility, muscle strength, goniometry, and pain. It appears to be a safe tool for accelerating recovery in THA patients. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov; NCT01491048.
Effect of biofertilizers vs perfected chemical fertilization for sesame grown in summer rice fallow

In Kerala, summer rice fallow is a potential area for cultivation of short duration pulses and oil seeds, even though the crop may face soil moisture stress during the early growth stage. In intensive cropping systems, supplementing soil nutrients by the use of chemical fertilizer is considered inevitable for obtaining optimum yield of crops. But it has been observed that continuous use of chemical fertilizers may affect soil health and may lead to a negative impact on soil productivity. Hence, for sustainable agriculture, all our efforts should be streamlined to protect and maintain soil health. In this context, now-a-days biofertilizers are gaining importance in agriculture.
Conversing with electronic devices. An integrated approach towards the generation and evaluation of nonverbal behaviour in face-to-face like interface agents

This paper addresses fundamental research problems concerning the implementation of nonverbal communication channels in so-called conversational interfaces: As a solution to these problems a new methodology is introduced that makes possible the generation, systematic variation and experimental evaluation of nonverbally interacting interface agents in different task contexts. A taxonomy of research designs is presented and first applications of the new methodology are summarized and discussed.
Impact of Acute Rejection Episodes on Long‐Term Graft Survival Following Simultaneous Kidney‐Pancreas Transplantation

Although it is well established that acute rejection is one of the major risk factors for chronic graft loss following kidney transplantation, its effect on long‐term graft survival following simultaneous kidney‐pancreas transplants (SKPTs) is less well known. We analyzed a large cohort of SKPTs and cadaver kidney transplants reported to the United Network for Organ Sharing database during 1988–97, to determine the impact of acute rejection episodes on long‐term kidney and pancreas graft survival. Only patients whose kidney and pancreas grafts had survived for at least 1 year were included. Other potential risk factors influencing long‐term graft survival were included in the analysis. Of the 4251 SKPTs, 45% had no acute rejection, 36% had kidney only rejection, 3% had pancreas only rejection, and 16% had both kidney and pancreas rejection within the 1st year post transplant. The 5‐year kidney and pancreas graft survival rates adjusted for other risk factors were 91% and 85%, respectively; for those with no acute rejection episodes, 88% and 84%, respectively; for those with kidney only rejection, 94% and 83%, respectively; for those with pancreas only rejection; and 86% and 78%, respectively, for those with both kidney and pancreas rejection. The relative risk (RR) of kidney graft failure was 1.32 when acute rejection involved the kidney graft only, while the RR was 1.53 when the rejection involved both organs. We conclude that acute rejection episodes have a negative impact on the long‐term kidney graft survival in the SKPT population similar to that in the cadaver kidney transplant population. Patients who had acute rejection episodes of both kidney and pancreas have the worst long‐term graft survival.
Phenotype Specific Analyses Reveal Distinct Regulatory Mechanism for Chronically Activated p53

The downstream functions of the DNA binding tumor suppressor p53 vary depending on the cellular context, and persistent p53 activation has recently been implicated in tumor suppression and senescence. However, genome-wide information about p53-target gene regulation has been derived mostly from acute genotoxic conditions. Using ChIP-seq and expression data, we have found distinct p53 binding profiles between acutely activated (through DNA damage) and chronically activated (in senescent or pro-apoptotic conditions) p53. Compared to the classical ‘acute’ p53 binding profile, ‘chronic’ p53 peaks were closely associated with CpG-islands. Furthermore, the chronic CpG-island binding of p53 conferred distinct expression patterns between senescent and pro-apoptotic conditions. Using the p53 targets seen in the chronic conditions together with external high-throughput datasets, we have built p53 networks that revealed extensive self-regulatory ‘p53 hubs’ where p53 and many p53 targets can physically interact with each other. Integrating these results with public clinical datasets identified the cancer-associated lipogenic enzyme, SCD, which we found to be directly repressed by p53 through the CpG-island promoter, providing a mechanistic link between p53 and the ‘lipogenic phenotype’, a hallmark of cancer. Our data reveal distinct phenotype associations of chronic p53 targets that underlie specific gene regulatory mechanisms.
Current Status of Gene Engineering Cell Therapeutics

Ex vivo manipulations of autologous patient’s cells or gene-engineered cell therapeutics have allowed the development of cell and gene therapy approaches to treat otherwise incurable diseases. These modalities of personalized medicine have already shown great promises including product commercialization for some rare diseases. The transfer of a chimeric antigen receptor or T cell receptor genes into autologous T cells has led to very promising outcomes for some cancers, and particularly for hematological malignancies. In addition, gene-engineered cell therapeutics are also being explored to induce tolerance and regulate inflammation. Here, we review the latest gene-engineered cell therapeutic approaches being currently explored to induce an efficient immune response against cancer cells or viruses by engineering T cells, natural killer cells, gamma delta T cells, or cytokine-induced killer cells and to modulate inflammation using regulatory T cells.
Effective HIV vaccine: narrow path to broadly neutralizing antibodies?

DOI:10.1097/COH.0000000000000371 The quest for a prophylactic vaccine against the human immunodeficiency virus is almost as old as the identification of HIV as the cause of the Acquired Immunodeficiency Syndrome (AIDS) in 1983 [1]. The elicitation of neutralizing antibodies (nAbs) by a vaccine is since believed to be imperative in either mediating sterilizing immunity or at least in preventing the establishment of latent reservoirs. Initial optimism was raised in the early 1990s when it was reported that vaccination with antigen preparations including whole inactivated virus, purified recombinant envelope (Env) proteins, and envelope-derived V3-specific peptides led to protection or a significant delay of infection of chimpanzees from a close to homologous i.v. challenge with a labadapted virus strain (HIV-1 IIIB) [2]. The clinical outcome was at that time attributed to sustained and high titers of virus neutralizing antibodies. These initial signs of hope, however, quickly gave way to fundamental sobering upon findings from numerous preclinical and clinical studies, including two phase III efficacy trials (VAX003 and VAX004), which proved that the neutralizing antibody responses induced by Env containing vaccine preparations such as the recombinant gp120s (AIDSVAX B/B and AIDSVAX B/E) used in the two phase III trials were largely strain-specific, lacked breadth and failed to neutralize primary isolates [3]. In this issue, 14 articles report about recent observations from large clinical cohort studies and vaccine trials. Special emphasis has been put on lessons learned from the plethora of broadly neutralizing monoclonal antibodies that were isolated from elite neutralizers over the last 5 years regarding their potential use in therapeutic and prophylactic settings, the ontology of envelope specific B-cell development, the envelope immunogen design, and ultimately the development of knock-in mice producing human antibodies to support the testing of novel vaccine concepts. The first contribution in this issue summarizes key findings from large clinical cohort studies analysis revealing that 10–30% of HIV infections result in some level of serum neutralization breadth. Only less than 10% of individuals seem to develop a
Diagnostic accuracy of fecal lactoferrin for inflammatory bowel disease: a meta-analysis.

OBJECTIVE To do a systematic review using meta-analysis to assess the diagnostic accuracy of fecal lactoferrin (FL) in patients with inflammatory bowel disease (IBD). METHODS We performed a literature review and systematically searched the Medline and EMBASE databases for eligible studies. The quality of the included studies was assessed using the QUADAS tool. The sensitivity, specificity, and other diagnostic indexes of FL were pooled using a random-effects model. RESULTS Seven studies, involving 1816 patients, met the inclusion criteria. In all studies, the pooled FL sensitivity and pooled specificity were 0.82 (95% confidence interval [CI]: 0.72, 0.89) and 0.95 (95% CI: 0.88, 0.98), respectively. The positive and negative likelihood ratios were 16.63 and 0.18, respectively. The area under the summary receiver-operating characteristic curve (SROC) was 0.95 (95% CI: 0.93, 0.97), and the diagnostic odds ratio was 90.04 (95% CI: 37.01, 219.02). The pooled FL sensitivity and specificity for Crohn's disease (CD) diagnosis (sensitivity =75%, specificity =100%) was not as good as it was for ulcerative colitis (UC) diagnosis (sensitivity =82%, specificity =100%). CONCLUSION FL, as a noninvasive and screening marker, has a high specificity and a modest specificity during the diagnosis of suspected IBD.
HARAQ: Congestion-Aware Learning Model for Highly Adaptive Routing Algorithm in On-Chip Networks

The occurrence of congestion in on-chip networks can severely degrade the performance due to increased message latency. In mesh topology, minimal methods can propagate messages over two directions at each switch. When shortest paths are congested, sending more messages through them can deteriorate the congestion condition considerably. In this paper, we present an adaptive routing algorithm for on-chip networks that provide a wide range of alternative paths between each pair of source and destination switches. Initially, the algorithm determines all permitted turns in the network including 180-degree turns on a single channel without creating cycles. The implementation of the algorithm provides the best usage of all allowable turns to route messages more adaptively in the network. On top of that, for selecting a less congested path, an optimized and scalable learning method is utilized. The learning method is based on local and global congestion information and can estimate the latency from each output channel to the destination region.
Neurobiology of Mice Selected for High Voluntary Wheel-running Activity1

Abstract Selective breeding of house mice has been used to study the evolution of locomotor behavior. Our model consists of 4 replicate lines selectively bred for high voluntary wheel running (High-Runner) and 4 bred randomly (Control). The major changes in High-Runner lines appear to have taken place in the brain rather than in capacities for exercise. Their neurobiological profile resembles features of human Attention Deficit Hyperactivity Disorder (ADHD) and is also consistent with high motivation for exercise as a natural reward. Both ADHD and motivation for natural rewards (such as food and sex), as well as drugs of abuse, have been associated with alterations in function of the neuromodulator dopamine, and High-Runner mice respond differently to dopamine drugs. In particular, drugs that block the dopamine transporter protein (such as Ritalin and cocaine) reduce the high-intensity running of High-Runner mice but have little effect on Control mice. In preliminary studies of mice exercised on a treadmill, brain dopamine concentrations did not differ, suggesting that changes in the dopamine system may have occurred downstream of dopamine production (e.g., receptor expression or transduction). Brain imaging by immunohistochemical detection of c-Fos identified several key regions (prefrontal cortex, nucleus accumbens, caudate-putamen, lateral hypothalamus) that appear to play a role in the differential response to Ritalin and in the increased motivation for running in High-Runner mice. The activation of other brain regions, such as the hippocampus, was closely associated with wheel running itself. Chronic wheel running (several weeks) also increased the production of new neurons to apparently maximal levels in the hippocampus, but impaired learning in High-Runner mice. We discuss the biomedical implications of these findings.