Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of Xenopus Tissue Inhibitor of Metalloproteinases-2: A Role in Regulating Matrix Metalloproteinase Activity during Development

Background Frog metamorphosis is totally dependent on thyroid hormone (T3) and mimics the postembryonic period around birth in mammals. It is an excellent model to study the molecular basis of postembryonic development in vertebrate. We and others have shown that many, if not all, matrix metalloproteinases (MMPs), which cleave proteins of the extracellular matrix as well as other substrates, are induced by T3 and important for metamorphosis. MMP activity can be inhibited by tissue inhibitors of metalloproteinase (TIMPs). There are 4 TIMPs in vertebrates and their roles in postembryonic development are poorly studied. Methodology/Principal Findings We analyzed the TIMP2 genes in Xenopus laevis and the highly related species Xenopus tropicalis and discovered that TIMP2 is a single copy gene in Xenopus tropicalis as in mammals but is duplicated in Xenopus laevis. Furthermore, the TIMP2 locus in Xenopus tropicalis genome is different from that in human, suggesting an evolutionary reorganization of the locus. More importantly, we found that the duplicated TIMP2 genes were similarly regulated in the developing limb, remodeling intestine, resorbing tail during metamorphosis. Unexpectedly, like its MMP target genes, the TIMP2 genes were upregulated by T3 during both natural and T3-induced metamorphosis. Conclusions/Significance Our results indicate that TIMP2 is highly conserved among vertebrates and that the TIMP2 locus underwent a chromosomal reorganization during evolution. Furthermore, the unexpected upregulation of TIMP2 genes during metamorphosis suggests that proper balance of MMP activity is important for metamorphosis.
The MiR-495/Annexin A3/P53 Axis Inhibits the Invasion and EMT of Colorectal Cancer Cells

Background/Aims: More and more reports have shown that the dysregulation of miRNAs can contribute to the progression and metastasis of human cancers. Many studies have shown that the down-regulation of the miR-495 level occurs in a variety of cancers, including colorectal cancer (CRC). However, the precise molecular mechanisms of miR-495 in CRC have not been well clarified. In the current study, we investigated the biological functions and molecular mechanisms of miR-495 in CRC cell lines. Methods: qRT-PCR was used to determine the level of miR-495 in CRC cell lines and tissues. A miR-495 mimic and inhibitor were transfected into CRC cells, and the effects of miR-495 on the invasion and EMT were explored by qRT-PCR as well as transwell and Western blot assays. Meanwhile, luciferase assays were performed to validate Annexin A3 as a miR-495 target in CRC cells. Results: In our study, we found that miR-495 is down-regulated in CRC tissues and cell lines. Moreover, the low level of miR-495 was associated with increased expression of Annexin A3 in CRC tissues and cell lines. The invasion and EMT of CRC cells were suppressed by the overexpression of miR-495. However, the down-regulation of miR-495 promoted the invasion and EMT of CRC cells. Bioinformatics analysis predicted that Annexin A3 was a potential target gene of miR-495. Next, the luciferase reporter assay confirmed that miR-495 could directly target Annexin A3. Consistent with the effect of miR-495, the down-regulation of Annexin A3 by siRNA inhibited the invasion and EMT of CRC cells through the up-regulation of p53. The introduction of Annexin A3 in CRC cells partially blocked the effects of the miR-495 mimic. Conclusion: The introduction of miR-495 directly targeted Annexin A3 to inhibit the invasion and EMT of CRC cells by up-regulating p53, and the down-regulation of Annexin A3 was essential for inhibiting the invasion and EMT of CRC cells by overexpressing miR-495. Overall, the re-activation of the miR-495/Annexin A3/ p53 axis may represent a new strategy for overcoming metastasis of CRC.
EPHA2 Polymorphisms and Age-Related Cataract in India

Objective We investigated whether previously reported single nucleotide polymorphisms (SNPs) of EPHA2 in European studies are associated with cataract in India. Methods We carried out a population-based genetic association study. We enumerated randomly sampled villages in two areas of north and south India to identify people aged 40 and over. Participants attended a clinical examination including lens photography and provided a blood sample for genotyping. Lens images were graded by the Lens Opacification Classification System (LOCS III). Cataract was defined as a LOCS III grade of nuclear ≥4, cortical ≥3, posterior sub-capsular (PSC) ≥2, or dense opacities or aphakia/pseudophakia in either eye. We genotyped SNPs rs3754334, rs7543472 and rs11260867 on genomic DNA extracted from peripheral blood leukocytes using TaqMan assays in an ABI 7900 real-time PCR. We used logistic regression with robust standard errors to examine the association between cataract and the EPHA2 SNPs, adjusting for age, sex and location. Results 7418 participants had data on at least one of the SNPs investigated. Genotype frequencies of controls were in Hardy-Weinberg Equilibrium (p>0.05). There was no association of rs3754334 with cataract or type of cataract. Minor allele homozygous genotypes of rs7543472 and rs11260867 compared to the major homozygote genotype were associated with cortical cataract, Odds ratio (OR) = 1.8, 95% Confidence Interval (CI) (1.1, 3.1) p = 0.03 and 2.9 (1.2, 7.1) p = 0.01 respectively, and with PSC cataract, OR = 1.5 (1.1, 2.2) p = 0.02 and 1.8 (0.9, 3.6) p = 0.07 respectively. There was no consistent association of SNPs with nuclear cataract or a combined variable of any type of cataract including operated cataract. Conclusions Our results in the Indian population agree with previous studies of the association of EPHA2 variants with cortical cataracts. We report new findings for the association with PSC which is particularly prevalent in Indians.
Dose–response relationship between sports activity and musculoskeletal pain in adolescents

Abstract Physical activity has multiple health benefits but may also increase the risk of developing musculoskeletal pain (MSP). However, the relationship between physical activity and MSP has not been well characterized. This study examined the dose–response relationship between sports activity and MSP among adolescents. Two school-based serial surveys were conducted 1 year apart in adolescents aged 12 to 18 years in Unnan, Japan. Self-administered questionnaires were completed by 2403 students. Associations between time spent in organized sports activity and MSP were analyzed cross-sectionally (n = 2403) and longitudinally (n = 374, students free of pain and in seventh or 10th grade at baseline) with repeated-measures Poisson regression and restricted cubic splines, with adjustment for potential confounders. The prevalence of overall pain, defined as having pain recently at least several times a week in at least one part of the body, was 27.4%. In the cross-sectional analysis, sports activity was significantly associated with pain prevalence. Each additional 1 h/wk of sports activity was associated with a 3% higher probability of having pain (prevalence ratio = 1.03, 95% confidence interval = 1.02-1.04). Similar trends were found across causes (traumatic and nontraumatic pain) and anatomic locations (upper limbs, lower back, and lower limbs). In longitudinal analysis, the risk ratio for developing pain at 1-year follow-up per 1 h/wk increase in baseline sports activity was 1.03 (95% confidence interval = 1.02-1.05). Spline models indicated a linear association (P < 0.001) but not a nonlinear association (P ≥ 0.45). The more the adolescents played sports, the more likely they were to have and develop pain.
Breast cancer screening in women with mental illness: comparative meta-analysis of mammography uptake.

BACKGROUND There is a higher mortality rate due to cancer in people with mental illness and previous work suggests suboptimal medical care in this population. It remains unclear if this extends to breast cancer population screening. AIMS To conduct a systematic review and meta-analysis to establish if women with a mental health condition are less likely to receive mammography screening compared with those without mental ill health. METHOD Major electronic databases were searched from inception until February 2014. We calculated odds ratios (OR) with a random effects meta-analysis comparing mammography screening rates among women with and without a mental illness. Results were stratified according to primary diagnosis including any mental illness, mood disorders, depression, severe mental illness (SMI), distress and anxiety. RESULTS We identified 24 publications reporting breast cancer screening practices in women with mental illness (n = 715,705). An additional 5 studies investigating screening for those with distress (n = 21,491) but no diagnosis of mental disorder were identified. The pooled meta-analysis showed significantly reduced rates of mammography screening in women with mental illness (OR = 0.71, 95% CI 0.66-0.77), mood disorders (OR = 0.83, 95% CI 0.76-0.90) and particularly SMI (OR = 0.54, 95% CI 0.45-0.65). No disparity was evident among women with distress alone. CONCLUSIONS Rates of mammography screening are lower in women with mental illness, particularly women with SMI, and this is not explained by the presence of emotional distress. Disparities in medical care due to mental illness clearly extend into preventive population screening.
Multi Robot Path Planning and Path Coordination Using Genetic Algorithms: Extended Abstract

Planning optimal paths for multiple robots is computationally expensive. In this research, we provide a Genetic Algorithm implementation for multi robot path planning. Path planning for multiple mobile robots must devise a collision-free path for each robot. The paper presents a Genetic Algorithm multi robot path planner that we developed to provide a solution to the problem. Experimental results using m3pi robots confirm the usefulness of the proposed solution in a variety of scenarios such as multi robot navigation as well as scenarios that require coordination of multiple robots to achieve a common goal such as pushing a box or trapping a prey.
Histological Evidence of the Osseointegration of Fractured Direct Metal Laser Sintering Implants Retrieved after 5 Years of Function

Background Direct metal laser sintering (DMLS) is an additive manufacturing technique that allows the fabrication of dental implants layer by layer through the laser fusion of titanium microparticles. The surface of DMLS implants is characterized by a high open porosity with interconnected pores of different sizes; therefore, it has the potential to enhance and accelerate bone healing. To date, however, there are no histologic/histomorphometric studies in the literature evaluating the interface between bone and DMLS implants in the long-term. Purpose To evaluate the interface between bone and DMLS implants retrieved after 5 years of functional loading. Methods Two fractured DMLS implants were retrieved from the human jaws, using a 5 mm trephine bur. Both the implants were clinically stable and functioned regularly before fracture. The specimens were processed for histologic/histomorphometric evaluation; the bone-to-implant contact (BIC%) was calculated. Results Compact, mature lamellar bone was found over most of the DMLS implants in close contact with the implant surface; the histomorphometric evaluation showed a mean BIC% of 66.1% (±4.5%). Conclusions The present histologic/histomorphometric study showed that DMLS implants were well integrated in bone, after 5 years of loading, with the peri-implant bone undergoing continuous remodeling at the interface.
An entropic barriers diffusion theory of decision-making in multiple alternative tasks

We present a theory of decision-making in the presence of multiple choices that departs from traditional approaches by explicitly incorporating entropic barriers in a stochastic search process. We analyze response time data from an on-line repository of 15 million blitz chess games, and show that our model fits not just the mean and variance, but the entire response time distribution (over several response-time orders of magnitude) at every stage of the game. We apply the model to show that (a) higher cognitive expertise corresponds to the exploration of more complex solution spaces, and (b) reaction times of users at an on-line buying website can be similarly explained. Our model can be seen as a synergy between diffusion models used to model simple two-choice decision-making and planning agents in complex problem solving.
Bone Marrow NK1.1− and NK1.1+ T Cells Reciprocally Regulate Acute Graft versus Host Disease

Sorted CD4+ and CD8+ T cells from the peripheral blood or bone marrow of donor C57BL/6 (H-2b) mice were tested for their capacity to induce graft-versus-host disease (GVHD) by injecting the cells, along with stringently T cell–depleted donor marrow cells, into lethally irradiated BALB/c (H-2d) host mice. The peripheral blood T cells were at least 30 times more potent than the marrow T cells in inducing lethal GVHD. As NK1.1+ T cells represented <1% of all T cells in the blood and ∼30% of T cells in the marrow, the capacity of sorted marrow NK1.1− CD4+ and CD8+ T cells to induce GVHD was tested. The latter cells had markedly increased potency, and adding back marrow NK1.1+ T cells suppressed GVHD. The marrow NK1.1+ T cells secreted high levels of both interferon γ (IFN-γ) and interleukin 4 (IL-4), and the NK1.1− T cells secreted high levels of IFN-γ with little IL-4. Marrow NK1.1+ T cells obtained from IL-4−/− rather than wild-type C57BL/6 donors not only failed to prevent GVHD but actually increased its severity. Together, these results demonstrate that GVHD is reciprocally regulated by the NK1.1− and NK1.1+ T cell subsets via their differential production of cytokines.
KNN-based Image Annotation by Collectively Mining Visual and Semantic Similarities

The aim of image annotation is to determine labels that can accurately describe the semantic information of images. Many approaches have been proposed to automate the image annotation task while achieving good performance. However, in most cases, the semantic similarities of images are ignored. Towards this end, we propose a novel Visual-Semantic Nearest Neighbor (VS-KNN) method by collectively exploring visual and semantic similarities for image annotation. First, for each label, visual nearest neighbors of a given test image are constructed from training images associated with this label. Second, each neighboring subset is determined by mining the semantic similarity and the visual similarity. Finally, the relevance between the images and labels is determined based on maximum a posteriori estimation. Extensive experiments were conducted using three widely used image datasets. The experimental results show the effectiveness of the proposed method in comparison with state-of-the-arts methods.
Vasculogenesis and Diabetic Erectile Dysfunction: How Relevant Is Glycemic Control?

Erectile dysfunction (ED) is a complication of diabetes, condition responsible for causing endothelial dysfunction (EDys) and hampering repair mechanisms. However, scarce information is available linking vasculogenesis mediated by Endothelial Progenitor Cells (EPCs) and diabetes‐associated ED. Furthermore, it remains to be elucidated if glycemic control plays a role on EPCs functions, EPCs modulators, and penile vascular health. We evaluated the effects of diabetes and insulin therapy on bone marrow (BM) and circulating EPCs, testosterone, and systemic/penile Stromal Derived Factor‐1 alpha (SDF‐1α) expression. Male Wistar rats were divided into groups: age‐matched controls, 8‐weeks streptozotocin‐induced type 1 diabetics, and insulin‐treated 8‐weeks diabetics. EPCs were identified by flow cytometry for CD34/CD133/VEGFR2/CXCR4 antigens. Systemic SDF‐1α and testosterone levels were evaluated by ELISA. Penile SDF‐1α protein expression was assessed, in experimental and human diabetic cavernosal samples, by immunohistochemical techniques. Diabetic animals presented a reduction of BM‐derived EPCs and an increase in putative circulating endothelial cells (CECs) sloughed from vessels wall. These alterations were rescued by insulin therapy. In addition, glycemic control promoted an increase in systemic testosterone and SDF‐1α levels, which were significantly decreased in animals with diabetes. SDF‐1α protein expression was reduced in experimental and human cavernosal diabetic samples, an effect prevented by insulin in treated animals. Insulin administration rescued the effects of diabetes on BM function, CECs levels, testosterone, and plasmatic/penile SDF‐1α protein expression. This emphasizes the importance of glycemic control in the prevention of diabetes‐induced systemic and penile EDys, by the amelioration of endothelial damage, and increase in protective pathways. J. Cell. Biochem. 118: 82–91, 2017. © 2016 Wiley Periodicals, Inc.
Host responses to intestinal nematodes

Helminth infection remains common in developing countries, where residents who suffer from the consequences of such infections can develop serious physical and mental disorders and often persist in the face of serious economic problems. Intestinal nematode infection induces the development of Th2-type immune responses including the B-cell IgE response; additionally, this infection induces an increase in the numbers and activation of various types of effector cells, such as mast cells, eosinophils and basophils, as well as the induction of goblet cell hyperplasia, anti-microbial peptide production and smooth-muscle contraction, all of which contribute to expel nematodes. Innate immunity is important in efforts to eliminate helminth infection; cytokines, including IL-25, IL-33 and thymic stromal lymphopoietin, which are products of epithelial cells and mast cells, induce Th2 cells and group 2 innate lymphoid cells to proliferate and produce Th2 cytokines. Nematodes also facilitate chronic infection by suppression of immune reactions through an increased number of Treg cells. Immunosuppression by parasite infection may ultimately be beneficial for the host animals; indeed, a negative correlation has been found between parasite infection and the prevalence of inflammatory disease in humans.
Defining the Outcome of Ventricular Tachycardia Ablation: Timing and Value of Programmed Ventricular Stimulation

Background: Catheter ablation of ventricular tachycardia (VT) is effective to prevent arrhythmia episode–related implantable cardioverter defibrillator shocks. However, recurrences in noninducible patients at programmed ventricular stimulation (PVS) are substantial. Methods and Results: From May 2013 to September 2015, 218 PVSs were performed 6 days (5–7) after ablation (186 noninvasive programmed stimulations and 32 invasive PVS) in 210 consecutive patients (ischemic, 48%; median left ventricular ejection fraction, 37%; syncope, 35% with trauma associated 6%), while patients were awake and under &bgr;-blocker therapy. After ablation, implantable cardioverter defibrillators were programmed according to noninvasive programmed stimulations results (class A—noninducible; class B—nondocumented inducible VT; and class C—documented inducible VT), with high and delayed VT detection intervals. Concordance between PVS end procedure and PVS day 6 was 67%. Positive predictive value and negative predictive value were higher for PVS day 6 (53% and 88% versus 43% and 71%). Ischemic and patients with preserved ejection fraction showed the highest negative predictive value (91% and 96%). Among 46 of 174 (26%) noninducible patients at PVS end procedure, but inducible at day 6, 59% had VT recurrence at 1-year follow-up; recurrences were 9% when both studies were noninducible. There were no inappropriate shocks; incidence of syncope was 3%; and none was harmful. The rate of appropriate shocks per patient per month according to noninvasive programmed stimulations results was significantly reduced, comparing the month before and after ablation (class A: 2 [0.75–4] versus 0; class B: 2 [1–4] versus 0; class C: 2 [1–4] versus 0; P<0.001). Conclusions: PVS at day 6 predicts VT recurrence more accurately allowing to identify patients who might benefit from a redo ablation and addressing implantable cardioverter defibrillator programming.
A Dialysis Patient's Choice and a Nephrologist's Obligation: The Need to Understand and Value the Patient's Perspective

Patient‐centered care is critical to the successful management of chronic diseases, such as chronic kidney disease. While a course of treatment may prolong life it may come with a reduced quality of life (QOL). For many patients, the decision to prolong life at the expense of lower QOL is not an obvious choice. Dialysis patients make treatment decisions daily, some of which can be life‐altering. Therefore, the need for optimal decision‐making may be more pressing in dialysis patients than in many other chronic disease states. Guiding patients through these life‐altering decisions requires a fuller understanding of how they view their disease, their treatments, and the consequence of accepting or rejecting the treatments offered to them. We propose a conceptual framework to help us understand decision‐making in chronic diseases such as end stage renal disease. We also highlight a need to critically examine how patients make decisions on survival versus QOL and the relationship of their decisions to their illness and treatment beliefs. Understanding the role of patients’ belief systems can guide education interventions for medical professionals involved in their care in order to help them develop patient‐centered, personalized treatment plans.
Genetic vasectomy—Overexpression of Prm1‐EGFP fusion protein in elongating spermatids causes dominant male sterility in mice

Transgenic mice are vital tools in both basic and applied research. Unfortunately, the transgenesis process as well as many other assisted reproductive techniques involving embryo transfer rely on vasectomized males to induce pseudopregnancy in surrogate mothers. Vasectomy is a surgical procedure associated with moderate pain and must be carried out under full anaesthesia by qualified personnel. Eliminating the need for vasectomy would be beneficial from the economic and animal welfare point of view. Our aim was to develop a transgene‐based alternative to the surgical vasectomy procedure. We generated several transgenic mouse lines expressing a Protamine‐1 (Prm1) EGFP fusion protein under the transcriptional and translational regulatory control of Prm1. Male mice from lines showing moderate transgene expression were fully fertile whereas strong overexpression of the Prm1‐EGFP fusion protein resulted in complete and dominant male sterility without affecting the ability to mate and to produce copulatory plugs. Sterility was due to impaired spermatid maturation affecting sperm viability and motility. Furthermore, sperm having high Prm1‐EGFP levels failed to support preimplantation embryonic development following Intracytoplasmic Sperm Injection (ICSI). The “genetic vasectomy system” was further improved by genetically linking the dominant male sterility to ubiquitous EGFP expression in the soma as an easy phenotypic marker enabling rapid genotyping of transgenic males and females. This double transgenic approach represents a reliable and cost‐effective “genetic vasectomy” procedure making the conventional surgical vasectomy methodology obsolete. genesis 48:151–160, 2010. © 2010 Wiley‐Liss, Inc.