Miracle-dz/UniFAR-FTUs huggingface dataset:
Topology based data analysis identifies a subgroup of breast cancers with a unique mutational profile and excellent survival

High-throughput biological data, whether generated as sequencing, transcriptional microarrays, proteomic, or other means, continues to require analytic methods that address its high dimensional aspects. Because the computational part of data analysis ultimately identifies shape characteristics in the organization of data sets, the mathematics of shape recognition in high dimensions continues to be a crucial part of data analysis. This article introduces a method that extracts information from high-throughput microarray data and, by using topology, provides greater depth of information than current analytic techniques. The method, termed Progression Analysis of Disease (PAD), first identifies robust aspects of cluster analysis, then goes deeper to find a multitude of biologically meaningful shape characteristics in these data. Additionally, because PAD incorporates a visualization tool, it provides a simple picture or graph that can be used to further explore these data. Although PAD can be applied to a wide range of high-throughput data types, it is used here as an example to analyze breast cancer transcriptional data. This identified a unique subgroup of Estrogen Receptor-positive (ER+) breast cancers that express high levels of c-MYB and low levels of innate inflammatory genes. These patients exhibit 100% survival and no metastasis. No supervised step beyond distinction between tumor and healthy patients was used to identify this subtype. The group has a clear and distinct, statistically significant molecular signature, it highlights coherent biology but is invisible to cluster methods, and does not fit into the accepted classification of Luminal A/B, Normal-like subtypes of ER+ breast cancers. We denote the group as c-MYB+ breast cancer.
Photodynamic therapy in the treatment of basal cell carcinoma

Photodynamic therapy (PDT) is a medical procedure based on the activation of the molecules of various exogenous or endogenous chemical substances called photosensitizers by a light source emitting radiation of an adequate wavelength, usually situated in the visible spectrum; photosensitizers are chemical compounds bearing the capacity to selectively concentrate in the neoplastic cells. The energy captured by the molecules of these substances pervaded in the tumor cells is subsequently discharged in the surrounding tissue, triggering certain photodynamic reactions that result in the destruction of the tumor. The procedure is applicable in numerous medical fields. Skin basal cell carcinoma (BCC), the most frequent type of cancer of the human species, is a cutaneous tumor that responds very well to this innovative treatment method. By reviewing numerous recent studies in the field, this article aims to present the role and the indications of photodynamic therapy in the management of basal cell carcinoma, as well as the most important results achieved so far by this therapy in the field of dermato-oncology.
Neurocognitive Outcome and White Matter Anisotropy in Childhood Acute Lymphoblastic Leukemia Survivors Treated with Different Protocols

Neurocognitive outcome affects the quality of life of ALL survivors. This study is aimed to assess the prevalence of neurocognitive dysfunction by psychometric and imaging tools in survivors of childhood ALL, treated with 3 different protocols and the effect of time elapsed since the end of chemotherapy. Sixty-two ALL survivors aged 6–18 years and treated in the period 1997–2007 and 60 healthy age and sex matched controls were subjected to neurocognitive testing using Wechsler Intelligence Scale for Children, Benton visual retention (BVRT) and Trail Making test (TMT), followed by diffusion weighed and diffusion tensor MRI for calculation of fraction anisotropy (FA). Survivors underwent revision of protocol and type of CNS therapy. Three different protocols were used: modified BFM 83, BFM 90, and CCG. Survivors treated with modified CCG protocol showed a significant decrease in all cognitive tests compared to control (p<.05); BFM 90 group had a significant lower IQ and longer TMT compared to both control and BFM 83 group and no significant difference was found in results of cognitive tests between BFM 83 and control group. Frontal FA was lower in CCG treated group compared to control, BFM 90 and BFM 83 groups (p<.05); meanwhile it was significantly lower in BFM 90 and BFM 83 groups compared to control group. We concluded that patients treated with modified CCG protocol showed the worst neurocognitive outcome among three assessed protocols. Frontal lobe FA might be an early marker for predicting the neurotoxicity in childhood ALL survivors.
The Inquiring Mind.

This inspiring book becomes one that is very booming. After published, this book can steal the market and book lovers to always run out of this book. And now, we will not let you run out any more to get this book. Why should be inquiring mind? As a book lover, you must know that enjoying the book to read should be relevant to how you exactly need now. If they are not too much relevance, you can take the way of the inspirations to create for new inspirations.
Comparison of zeroth- and first-order semi-discretizations for the delayed Mathieu equation

Semi-discretization method is applied to construct stability charts for periodic delay-differential equations. Zeroth-, improved zeroth- and first-order methods are used to construct approximate finite dimensional Floquet transition matrices for the delayed Mathieu equation and stability charts are determined. Since the stability boundaries of the delayed Mathieu equation are known in closed form, the convergence of different order approximations can be studied by computer simulations. Stability boundaries and computation times obtained by different time steps and different orders are compared.
Acute and Time-Course Effects of Traditional and Dynamic Warm-Up Routines in Young Elite Junior Tennis Players

Despite the large number of studies that have examined the acute effects of different warm up modalities (WU) on physical performance, none of them have documented the time course of potential performance recovery in tennis players. The aim of this study was twofold: (a) to analyze and compare the acute effects of two different WU modalities (traditional WU [TWU] and dynamic WU [DWU]) on physical performance (i.e., CMJ, sprint, serve speed and accuracy) in elite junior players, as well as (b) to monitor the time course of any WU-induced changes after 30 and 60 min of simulated match-play. Twelve junior elite players completed both WUs modalities (TWU and DWU) in a counterbalanced order on separate days. In each experimental session, counter movement jump (CMJ), 20-m sprint, tennis serve speed and accuracy tests were performed before (immediately after TWU or DWU) during (30 min) and after 60 min of a simulated match play. Measures were compared via four factorial (WU intervention and time) repeated measures ANOVAs. There were main effects of WU (TWU and DWU) throughout the time for all the variables analysed. The results indicate that DWU routine led to significantly faster 20 m sprint times and higher CMJs as well as faster and more accurate tennis serves at both post warm-up and 30 min match-play testing moments in comparison with the scores reported by the TWU routine (p < 0.05; positive effects with a probability of >75–99%). No significant intergroup differences were found at 60-min match-play testing moment in any variable (except for the 20 m sprint). Therefore, the findings of this study recommend for optimal performance in these elite tennis players, DWU routines should be performed prior to formal training and competition rather than TWU routines.
Anti-tumorigenicity of dietary α-mangostin in an HT-29 colon cell xenograft model and the tissue distribution of xanthones and their phase II metabolites.

SCOPE This study investigated the in vivo and in vitro activity of α-mangostin (α-MG), the most abundant xanthone in mangosteen pericarp, on HT-29 cell tumorigenicity, proliferation, and several markers of tumor cell activity, as well as the profile and amounts of xanthones in serum, tumor, liver, and feces. METHODS AND RESULTS Balb/c nu/nu mice were fed either control diet or diet containing 900 mg α-MG/kg. After 1 week of acclimation to diet, mice were injected subcutaneously with HT-29 cells and fed the same diets ad libitum for an additional 2 or 4 weeks. After 2 and 4 weeks, tumor mass and the concentrations of BcL-2 and β-catenin in tumors of mice fed diet with α-MG were significantly less than in mice fed control diet. Xanthones and their metabolites were identified in serum, tumor, liver, and feces. In vitro treatment of HT-29 cells with α-MG also inhibited cell proliferation and decreased expression of BcL-2 and β-catenin. CONCLUSION Our data demonstrate that the anti-neoplastic effect of dietary α-MG is associated with the presence of xanthones in the tumor tissue. Further investigation of the impact of beverages and food products containing xanthones on the prevention of colon cancer or as complementary therapy is merited.
Inhibition of Human Endothelial Cell Chemokine Production by the Opportunistic Fungal Pathogen Cryptococcus neoformans1

Cryptococcus neoformans is an encapsulated fungal pathogen commonly acquired by inhalation. Extrapulmonary dissemination can lead to infection of the bloodstream and various organs, most commonly resulting in meningoencephalitis. However, infection with C. neoformans is often characterized by a scant inflammatory response. The leukocyte response to infection depends in part upon a gradient of chemotactic factors and adhesion molecules expressed by the host vascular endothelium, yet the inflammatory response of human endothelial cells (EC) to C. neoformans has not been previously investigated. We found that incubation of primary human EC with C. neoformans did not induce chemokine synthesis, and resulted in differential inhibition of cytokine-induced IL-8, IFN-γ-inducible protein-10, and monocyte chemoattractant protein-1. In contrast, C. neoformans had little effect on EC surface expression of the leukocyte ligand, ICAM-1, as determined by flow cytometry. Modulation of chemokine production was dependent on the chemokine under study, the inoculum of C. neoformans used, fungal viability, and cell-cell contact, but independent of cryptococcal strain or encapsulation. These observations suggest a novel mechanism whereby C. neoformans can affect EC function and interfere with the host inflammatory response.
MavN is a Legionella pneumophila vacuole-associated protein required for efficient iron acquisition during intracellular growth

Significance Limiting access of intracellular iron to intracellular microbes is a critical arm of the nutritional immune response. Little is known about the mechanisms used by intravacuolar pathogens to overcome this attempted starvation. We show here that Legionella pneumophila employs its major virulence-associated secretion system to deliver a unique transmembrane protein into host cells during infection. Utilizing microscopic, biochemical, and transcriptional analysis of intracellular bacteria, we demonstrate that the MavN protein integrates into the host-derived vacuolar membrane and facilitates transport of essential iron into the lumen of the vacuole to promote bacterial growth. These findings shed light on what is likely to be a myriad of strategies used by bacteria to overcome potent host nutrient restrictions. Iron is essential for the growth and virulence of most intravacuolar pathogens. The mechanisms by which microbes bypass host iron restriction to gain access to this metal across the host vacuolar membrane are poorly characterized. In this work, we identify a unique intracellular iron acquisition strategy used by Legionella pneumophila. The bacterial Icm/Dot (intracellular multiplication/defect in organelle trafficking) type IV secretion system targets the bacterial-derived MavN (more regions allowing vacuolar colocalization N) protein to the surface of the Legionella-containing vacuole where this putative transmembrane protein facilitates intravacuolar iron acquisition. The ΔmavN mutant exhibits a transcriptional iron-starvation signature before its growth is arrested during the very early stages of macrophage infection. This intracellular growth defect is rescued only by the addition of excess exogenous iron to the culture medium and not a variety of other metals. Consistent with MavN being a translocated substrate that plays an exclusive role during intracellular growth, the mutant shows no defect for growth in broth culture, even under severe iron-limiting conditions. Putative iron-binding residues within the MavN protein were identified, and point mutations in these residues resulted in defects specific for intracellular growth that are indistinguishable from the ΔmavN mutant. This model of a bacterial protein inserting into host membranes to mediate iron transport provides a paradigm for how intravacuolar pathogens can use virulence-associated secretion systems to manipulate and acquire host iron.
CD26/dipeptidyl peptidase 4‐deficiency alters thymic emigration patterns and leukcocyte subsets in F344‐rats age‐dependently

As CD26 (dipeptidyl peptidase 4/DPP4) rapidly truncates incretins N‐terminally, including glucagon‐like peptide‐1, DPP4‐inhibitors have been developed for treatment of diabetes type 2. To some extent this is surprising, as CD26/DPP4 is also deeply involved in immune regulation. Long‐term pharmacological studies are hampered by off‐target inhibition of DPP4‐homologues. Therefore, we studied the effects of genetic CD26/DPP4‐deficiency by investigating blood, spleen and thymus leucocyte subpopulations of wild‐type and CD26‐deficient F344‐rats at different ages. In young animals at 1 and 3 months of age, there were no differences in leucocyte subsets, while in older animals the T cell composition was changed significantly. From the age of 6 months onwards, reduced numbers of recent thymic emigrants and memory T cells, and consequently an increased amount of naive T cells were observed in CD26‐deficient rats. In addition, the architecture of the thymus was altered, as observed by a reduced density of lymphocytes in the medulla. Furthermore, the number of proliferating cells in the thymus was decreased in CD26‐deficient rats at a higher age. Moreover, CD26‐deficiency resulted in markedly reduced numbers of B cells in later life. Additionally, an age‐ but not CD26‐dependent increase of regulatory T cells and a decrease of natural killer cell numbers were detected in the blood and spleen. Our findings indicate an important role of CD26 in maintaining lymphocyte composition, memory T cell generation and thymic emigration patterns during immunosenescence, with possible implications for using DPP4‐inhibitors.
A cross-sectional analysis of candidate biomarkers of biological effect in smokers, never-smokers and ex-smokers

Abstract Context: Biomarkers of biological effect (BOBE) have been proposed as potential tools to assess tobacco product use, toxicity and disease risk. Objective: To determine if candidate BOBE can distinguish between smokers, never-smokers and former smokers. Methods: Biomarker levels were compared from 143 smokers, 61 never-smokers and 61 ex-smokers. Results: In total, 27 candidate biomarkers were assessed, 14 were significantly different between smokers and never-smokers (p < 0.01) and of these 14 biomarkers, 12 were able to distinguish between smokers and former smokers (p < 0.05), which indicates the potential for reversibility. Conclusions: A total of 12 of 27 BOBE are potentially useful tools for future product assessment.
Discovering chimeric transcripts in paired-end RNA-seq data by using EricScript

MOTIVATION The discovery of novel gene fusions can lead to a better comprehension of cancer progression and development. The emergence of deep sequencing of trancriptome, known as RNA-seq, has opened many opportunities for the identification of this class of genomic alterations, leading to the discovery of novel chimeric transcripts in melanomas, breast cancers and lymphomas. Nowadays, few computational approaches have been developed for the detection of chimeric transcripts. Although all of these computational methods show good sensitivity, much work remains to reduce the huge number of false-positive calls that arises from this analysis. RESULTS We proposed a novel computational framework, named chimEric tranScript detection algorithm (EricScript), for the identification of gene fusion products in paired-end RNA-seq data. Our simulation study on synthetic data demonstrates that EricScript enables to achieve higher sensitivity and specificity than existing methods with noticeably lower running times. We also applied our method to publicly available RNA-seq tumour datasets, and we showed its capability in rediscovering known gene fusions.
Prescription audit in the inpatients of a tertiary care hospital attached with medical college

Background: Prescription audit is one of the methods to assess drug utilization and rationality of prescribing. Irrational prescribing is a worldwide problem. It is due to the faulty prescribing habits, lack of training amongst health care personnel, pressure from the pharmaceutical companies, and a lot of other reasons. Methods: The study was conducted by noting the details of patients admitted during 3 months from April to June 2015 in the Guru Gobind Singh Government Hospital, Jamnagar. Prescriptions were collected from the inpatients of medicine, surgery, obstetrics & gynecology, pediatrics, orthopedic randomly and analyzed according to the WHO core prescribing indicators. Results: Three hundred six prescriptions were analysed in which 1986 drugs were prescribed. Mean number of drugs per prescription was 6.49%. In our study, 63.34% drugs were prescribed by generic names and drugs on NLEM were 73.01%. Dosage forms used were mostly oral (69.54%). Infectious and parasitic diseases were the most common illnesses (16.01%) followed by diseases of respiratory system. The most common drug groups prescribed were GIT, antimicrobials, antihistaminics, multivitamins and minerals. The incidence of poly-pharmacy was also common with maximum number of prescriptions (26.8%) having 5 drugs per prescription. Conclusion: Prescription audit is an important measure to improve the quality of care afforded by the hospitals. Data generated on morbidity pattern coupled with current practices of treatment of these diseases provides an objective basis for preparing an NLEM. By this data we conclude that poly-pharmacy is quite common. Most of drugs were prescribed according to the NLEM 2011.
Transapical aortic valve implantation: The Vancouver experience.

INTRODUCTION Off-pump transapical aortic valve implantation (TA-TAVI) through mini-thoracotomy was first performed in Vancouver, Canada in October 2005. The objective of this manuscript is to describe the Vancouver experience with 178 TA-TAVI cases in symptomatic severe aortic stenosis (AS) since 2005. METHODS Baseline characteristics and in-hospital outcomes were calculated for the overall cohort. To compare pre-procedure and post-procedure echocardiographic measurements, one way analysis of variance was utilized, followed by Tukey's HSD. In-hospital outcomes were compared between early and late cohorts using Z-test and chi-squared test as appropriate. Kaplan-Meier analysis was used to generate 3-year survival curves. The Log-rank test was used to compare survival between low-risk and high-risk groups, based on STS score. RESULTS Between October 2005-March 2012, TA-TAVI was performed in 178 patients. Mean age was 80.5±8.6 years. Congestive heart failure and renal failure were more common in the late cohort, while previous myocardial infarction was more common in the early cohort (P<0.05). Eleven patients (6.2%) had significant intra-operative complications, including death (1.7%), conversion to CPB (3.9%), and valve embolization (1.1%). In-hospital survival was 87.9%. Mean length of hospital stay was 12.2±17.1 days. In-hospital incidence of stroke was 3.4%. Bleeding (20.2% vs. 4.7%) and vascular (14.6% vs. 3.5%) complications were more common in the early cohort. Echocardiography demonstrated a significant increase in aortic valve area and decrease in mean transvalvular gradient post-procedure. These improvements were maintained throughout the 3-year follow-up period. Overall survival was 72.1% at 6 months, 67.7% at 12 months, 55.5% at 24 months, and 47.3% at 36 months. Repeated Kaplan-Meier analysis for the 2 groups stratified by STS score, demonstrated improved survival in the low-risk group (Log-rank P=0.039). CONCLUSIONS Among patients with symptomatic severe AS at high risk for conventional AVR, TA-TAVI is a reasonable therapeutic option with acceptable risk. Long-term survival appears to be superior in lower-risk patients.
Specific Functions of BIG1 and BIG2 in Endomembrane Organization

Background Transport of molecules from one subcellular compartment to another involves the recruitment of cytosolic coat protein complexes to a donor membrane to concentrate cargo, deform the membrane and ultimately to form an independent carrier. Small-GTP-binding proteins of the Arf family are central to many membrane trafficking events. Arfs are activated by guanine nucleotide exchange factors (GEFs) which results in their recruitment to membranes and subsequent engagement with Arf-effectors, many of which are coat proteins. Among the human BFA-sensitive large Arf-GEFs, the function of the two closely related BIG1 and BIG2 is still not clear, and recent studies have raised the question of functional redundancy between the two proteins. Methodology/Principal Findings Here we have used small-interfering RNA on human cells and a combination of fixed and live-cell imaging to investigate the differential functions of BIG1 and BIG2 in endomembrane organization and function. Importantly, in this direct comparative study, we show discrete functions for BIG1 and BIG2. Our results show that depletion of BIG2 but not of BIG1 induces a tubulation of the recycling endosomal compartment, consistent with a specific role for BIG2 here. In contrast, suppression of BIG1 induces the formation of Golgi mini-stacks still polarized and functional in terms of cargo export. Conclusions A key finding from our work is that suppression of BIG1 expression results in a fragmentation of the Golgi apparatus. Our data indicate that the human BFA-sensitive large Arf-GEFs have non-redundant functions in cell organization and membrane trafficking. BIG1 is required to maintain the normal morphology of the Golgi; BIG2 is important for endosomal compartment integrity and cannot replace the function of BIG1 in Golgi organization.