Miracle-dz/UniFAR-FTUs huggingface dataset:
Recent Advances in the Management of Steroid Induced Osteoporosis

Correspondence to: Lai-Wa Kwok Abstract: Glucocorticoid-induced osteoporosis is the most common cause of drug-induced osteoporosis, leading to fragility fractures, decrease in mobility and quality of life. Patients who receive equivalent dose of prednisolone 5 mg for more than six months are at risk of glucocorticoid-induced osteoporosis, but there is no conclusive evidence for a safe cutoff for either dose or duration of steroid exposure and bone loss. The general view is 'dual action'. Both increased bone resorption and decreased bone formation contribute to the pathogenesis of glucocorticoid-induced osteoporosis. Glucocorticoids increase the expression of receptor activator of nuclear factor kB ligand (RANKL) and decrease the expression of its soluble receptor osteoprotegerin (OPG) in stromal and osteoblastic cells, leading to increased differentiation of pre-osteoclast to osteoclast. Fracture risk is related not only to bone mineral density, bone structural and mechanical properties, but also other clinical risk factors such as smoking, excessive alcohol, lack of exercises. Treatment threshold in glucocorticoid-induced osteoporosis is much lower than that in postmenopausal osteoporosis since fractures in glucocorticoid-induced osteoporosis occur at a higher bone mineral density than in postmenopausal osteoporosis. Bisphosphonates, being the first line therapy, have been shown to be effective in the prevention of vertebral fractures and they should be given together with adequate vitamin D and calcium supplement. The anabolic therapy parathyroid hormone, which targets on bone formation, has shown to be effective in increasing bone mineral density and reducing fractures and it may act as an alternative therapy.
Description of a Practitioner Model for Identifying Preferred Stimuli With Individuals With Autism Spectrum Disorders

The rich technology of stimulus preference assessment (SPA) is a product of 40 years of experimental research. Basic principles of reinforcement and a modest empirical literature suggest that high-preference stimuli identified via SPA may enhance treatment efficacy and decrease problem behavior more effectively than less-preferred stimuli. SPAs can be conducted using one of several methods associated with different time requirements and outcomes. Despite the broad applicability of preference assessments, we are unaware of widely available practitioner guidelines that prescribe when to use SPAs, how to select and modify specific SPA procedures, and how to supplement SPAs with other procedures for maximizing performance. The purpose of the current article is to describe a model for practitioners to select and conduct preference assessments based on practical considerations and research findings. Data are also reported from the application of the proposed model to preference assessments for 20 individuals diagnosed with autism spectrum disorders.
Pathways and mechanisms of venetoclax resistance

Abstract The approval of venetoclax, a ‘BH3-mimetic’ antagonist of the BCL-2 anti-apoptotic protein, for chronic lymphocytic leukemia represents a major milestone in translational apoptosis research. Venetoclax has already received ‘breakthrough’ designation for acute myeloid leukemia, and is being studied in many other tumor types. However, resistance to BCL-2 inhibitor monotherapy may rapidly ensue. Several studies have shown that the other two major anti-apoptotic BCL-2 family proteins, BCL-XL and MCL-1, are the main determinants of resistance to venetoclax. This opens up possibilities for rationally combining venetoclax with other targeted agents to circumvent resistance. Here, we summarize the most promising combinations, and highlight those already in clinical trials. There is also increasing recognition that different tumors display different degrees of addiction to individual BCL-2 family proteins, and of the need to refine current ‘BH3 profiling’ techniques. Finally, the successful clinical development of potent and selective antagonists of BCL-XL and MCL-1 is eagerly awaited.
Dissociable Behavioral, Physiological and Neural Effects of Acute Glucose and Fructose Ingestion: A Pilot Study

Previous research has revealed that glucose and fructose ingestion differentially modulate release of satiation hormones. Recent studies have begun to elucidate brain-gut interactions with neuroimaging approaches such as magnetic resonance imaging (MRI), but the neural mechanism underlying different behavioral and physiological effects of glucose and fructose are unclear. In this paper, we have used resting state functional MRI to explore whether acute glucose and fructose ingestion also induced dissociable effects in the neural system. Using a cross-over, double-blind, placebo-controlled design, we compared resting state functional connectivity (rsFC) strengths within the basal ganglia/limbic network in 12 healthy lean males. Each subject was administered fructose, glucose and placebo on three separate occasions. Subsequent correlation analysis was used to examine relations between rsFC findings and plasma concentrations of satiation hormones and subjective feelings of appetite. Glucose ingestion induced significantly greater elevations in plasma glucose, insulin, GLP-1 and GIP, while feelings of fullness increased and prospective food consumption decreased relative to fructose. Furthermore, glucose increased rsFC of the left caudatus and putamen, precuneus and lingual gyrus more than fructose, whereas within the basal ganglia/limbic network, fructose increased rsFC of the left amygdala, left hippocampus, right parahippocampus, orbitofrontal cortex and precentral gyrus more than glucose. Moreover, compared to fructose, the increased rsFC after glucose positively correlated with the glucose-induced increase in insulin. Our findings suggest that glucose and fructose induce dissociable effects on rsFC within the basal ganglia/limbic network, which are probably mediated by different insulin levels. A larger study would be recommended in order to confirm these findings.
Genome Diversification in Phylogenetic Lineages I and II of Listeria monocytogenes: Identification of Segments Unique to Lineage II Populations

ABSTRACT Thirteen different serotypes of Listeria monocytogenes can be distinguished on the basis of variation in somatic and flagellar antigens. Although the known virulence genes are present in all serotypes, greater than 90% of human cases of listeriosis are caused by serotypes 1/2a, 1/2b, and 4b and nearly all outbreaks of food-borne listeriosis have been caused by serotype 4b strains. Phylogenetic analysis of these three common clinical serotypes places them into two different lineages, with serotypes 1/2b and 4b belonging to lineage I and 1/2a belonging to lineage II. To begin examining evolution of the genome in these serotypes, DNA microarray analysis was used to identify lineage-specific and serotype-specific differences in genome content. A set of 44 strains representing serotypes 1/2a, 1/2b, and 4b was probed with a shotgun DNA microarray constructed from the serotype 1/2a strain 10403s. Clones spanning 47 different genes in 16 different contiguous segments relative to the lineage II 1/2a genome were found to be absent in all lineage I strains tested (serotype 4b and 1/2b) and an additional nine were altered exclusively in 4b strains. Southern hybridization confirmed that conserved alterations were, in all but two loci, due to absence of the segments from the genome. Genes within these contiguous segments comprise five functional categories, including genes involved in synthesis of cell surface molecules and regulation of virulence gene expression. Phylogenetic reconstruction and examination of compositional bias in the regions of difference are consistent with a model in which the ancestor of the two lineages had the 1/2 somatic serotype and the regions absent in the lineage I genome arose by loss of ancestral sequences.
Uterine Artery Velocity Waveforms as Predictors of Pregnancy Outcome in Patients with Antiphospholipid Syndrome

Abstract: In pregnant women, antiphospholipid syndrome (APS) is associated with an increased risk for preeclampsia, fetal intrauterine growth restriction, and other complications related to uteroplacental insufficiency. In normal pregnancy, impedance to flow in the uterine arteries decreases with gestation, as the likely consequence of the physiologic change of spiral arteries into low‐resistance vessels. The presence of antiphospholipid antibodies can impair this vascular adaptation, resulting in a reduced placental perfusion. Doppler investigation provides a noninvasive method for the study of uteroplacental blood flow. Several studies were performed to detect the predictive role of uterine artery Doppler velocimetry in relation to pregnancy outcome in APS patients. In some studies, a high resistance index in the uterine arteries strongly predicted the subsequent development of obstetric complications. In other studies, persistent bilateral uterine artery notches identified the risk of preeclampsia and fetal intrauterine growth restriction. To date, the uterine artery Doppler velocimetry resulted to be a useful tool for identifying APS pregnancies at risk for adverse pregnancy outcome. These findings might have important implications for the management of these patients.
Increased cAMP Levels Modulate Transforming Growth Factor-β/Smad-induced Expression of Extracellular Matrix Components and Other Key Fibroblast Effector Functions

cAMP is a key messenger of many hormones and neuropeptides, some of which modulate the composition of extracellular matrix. Treatment of human dermal fibroblasts with dibutyryl cyclic AMP and forskolin antagonized the inductive effects of transforming growth factor-β (TGF-β) on the expression of collagen, connective tissue growth factor, tissue inhibitor of matrix metalloproteinase-1, and plasminogen activator inhibitor type I, four prototypical TGF-β-responsive genes. Increased intracellular cAMP prevented TGF-β-induced Smad-specific gene transactivation, although TGF-β-mediated Smad phosphorylation and nuclear translocation remained unaffected. However, increased cAMP levels abolished TGF-β-induced interaction of Smad3 with its transcriptional co-activator cAMP-response element-binding protein (CREB)-binding protein (CBP)/p300. Overexpression of the transcriptional co-activator CBP/p300 rescued Smad-specific gene transcription in the presence of cAMP suggesting that sequestration of limited amounts of CBP/p300 by the activated cAMP/CREB pathway is the molecular basis of this inhibitory effect. These findings were extended by two functional assays. Increased intracellular cAMP levels suppressed the inductive activity of TGF-β to contract mechanically unloaded collagen lattices and resulted in an attenuation of fibroblast migration of mechanically induced cell layer wounds. Of note, cAMP and TGF-β synergistically induced hyaluronan synthase 2 (HAS2) expression and hyaluronan secretion, presumably via putative CREB-binding sites adjacent to Smad-binding sites within the HAS2 promoter. Our findings identify the cAMP pathway as a potent but differential and promoter-specific regulator of TGF-β-mediated effects involved in extracellular matrix homeostasis.
Acquisition of telomere repeat sequences by transfected DNA integrated at the site of a chromosome break

Previous analysis of plasmid DNA transfected into 108 cell clones demonstrated extensive polymorphism near the integration site in one clone. This polymorphism was apparent by Southern blot analysis as diffuse bands that extended over 30 kb. In the present study, nucleotide sequence analysis of cloned DNA from the integration site revealed telomere repeat sequences at the ends of the integrated plasmid DNA. The telomere repeat sequences at one end were located at the junction between the plasmid and cell DNA. The telomere repeat sequences at the other end were located in the opposite orientation in the polymorphic region and were shown by digestion with BAL 31 to be at the end of the chromosome. Telomere repeat sequences were not found at this location in the plasmid or parent cell DNA. Although the repeat sequences may have been acquired by recombination, a more likely explanation is that they were added to the ends of the plasmid by telomerase before integration. Comparison of the cell DNA before and after integration revealed that a chromosome break had occurred at the integration site, which was shown by fluorescent in situ hybridization to be located near the telomere of chromosome 13. These results demonstrate that chromosome breakage and rearrangement can result in interstitial telomere repeat sequences within the human genome. These sequences could promote genomic instability, because short repeat sequences can be recombinational hotspots. The results also show that DNA rearrangements involving telomere repeat sequences can be associated with chromosome breaks. The introduction of telomere repeat sequences at spontaneous or ionizing radiation-induced DNA strand breaks may therefore also be a mechanism of chromosome fragmentation.
A random matrix analysis and improvement of semi-supervised learning for large dimensional data

This article provides an original understanding of the behavior of a class of graph-oriented semi-supervised learning algorithms in the limit of large and numerous data. It is demonstrated that the intuition at the root of these methods collapses in this limit and that, as a result, most of them become inconsistent. Corrective measures and a new data-driven parametrization scheme are proposed along with a theoretical analysis of the asymptotic performances of the resulting approach. A surprisingly close behavior between theoretical performances on Gaussian mixture models and on real datasets is also illustrated throughout the article, thereby suggesting the importance of the proposed analysis for dealing with practical data. As a result, significant performance gains are observed on practical data classification using the proposed parametrization.
Constrained Monotone  $k$ -Submodular Function Maximization Using Multiobjective Evolutionary Algorithms With Theoretical Guarantee

The problem of maximizing monotone ${k}$ -submodular functions under a size constraint arises in many applications, and it is NP-hard. In this paper, we propose a new approach which employs a multiobjective evolutionary algorithm to maximize the given objective and minimize the size simultaneously. For general cases, we prove that the proposed method can obtain the asymptotically tight approximation guarantee, which was also achieved by the greedy algorithm. Moreover, we further give instances where the proposed approach performs better than the greedy algorithm on applications of influence maximization, information coverage maximization, and sensor placement. Experimental results on real-world data sets exhibit the superior performance of the proposed approach.
Blind hyperspectral unmixing

Hyperspectral unmixing methods aim at the decomposition of a hyperspectral image into a collection endmember signatures, i.e., the radiance or reflectance of the materials present in the scene, and the correspondent abundance fractions at each pixel in the image. This paper introduces a new unmixing method termed dependent component analysis (DECA). This method is blind and fully automatic and it overcomes the limitations of unmixing methods based on Independent Component Analysis (ICA) and on geometrical based approaches. DECA is based on the linear mixture model, i.e., each pixel is a linear mixture of the endmembers signatures weighted by the correspondent abundance fractions. These abundances are modeled as mixtures of Dirichlet densities, thus enforcing the non-negativity and constant sum constraints, imposed by the acquisition process. The endmembers signatures are inferred by a generalized expectation-maximization (GEM) type algorithm. The paper illustrates the effectiveness of DECA on synthetic and real hyperspectral images.
POROSITY OF ISOLATED CELL WALLS OF SACCHAROMYCES CEREVISIAE AND BACILLUS MEGATERIUM

Gerhardt, Philipp (The University of Michigan, Ann Arbor), and Jean A. Judge. Porosity of isolated cell walls of a yeast and a bacillus. J. Bacteriol. 87:945–951. 1964. —Decagram masses of cell walls were isolated from Saccharomyces cerevisiae and Bacillus megaterium; their porosity was examined by measuring the extent of uptake with polyethylene glycols and dextrans varying in molecular weight from 62 to 2,000,000. The results indicated that both walls are heteroporous. The near equality of extrapolated water-uptake values and determined moisture contents suggested that water in the cell walls is mainly free for distribution of solutes. Polymers with molecular weights of 4,500 and above were excluded by the yeast walls, and those with molecular weights of 57,000 were excluded by the bacillus walls; from these results, maximal openings of 36 and 107 A, respectively, were calculated. Electron micrographs of shadowed, stained, and sectioned walls revealed fine structure not inconsistent with heteroporosity, but the predicted openings were not seen. Altogether, in structure and permeability behavior, the cell walls were like a random meshwork of cross-linked macromolecular strands.
Excision of N-myc from chromosome 2 in human neuroblastoma cells containing amplified N-myc sequences

Amplification of one of three growth-stimulating myc genes is a common method by which many tumor types gain a proliferative advantage. In metastatic human neuroblastoma, the amplification of the N-myc locus, located on chromosome 2, is a dominant feature of this usually fatal pediatric cancer. Of the many models proposed to explain this amplification, all incorporate as the initial step either disproportionate overreplication of the chromosomal site or recombination across a loop structure. The original locus is retained within the chromosome in the overreplication models but is excised in the recombination models. To test these models, we have used somatic cell hybrids to separate and analyze the chromosomes 2 from a neuroblastoma cell line containing in vivo amplified N-myc. Our results demonstrate that N-myc is excised from one of the chromosomes, suggesting that deletion is a requisite part of gene amplification in a naturally occurring system.
Human uterodomes (pinopods) do not display pinocytotic function.

BACKGROUND The term 'pinopod' or 'pinopode' has been used indiscriminately since the 1970s to describe most apical structures on uterine epithelial cells and as such suggests a cross species structural functionality. This study looks at the apical cellular protrusions in rats and humans and compares their pinocytotic ability. METHODS We have utilized standard tracer techniques in an attempt to determine the functionality of the uterine surface protrusions in the human based on results reported in rats. RESULTS Pinopods in rat tissue demonstrated tracer uptake, but no tracer uptake in the apical protrusions of human uterine epithelium was evident. CONCLUSIONS These findings indicate that the uterine surface protrusions observed in the human are not pinocytotic and therefore probably perform a function different from similar structures observed in rats and mice. This highlights the need to alter nomenclature from pinopods to uterodomes.
Effect of Different Phases of Menstrual Cycle on Cardio-respiratory Efficiency in Normal, Overweight and Obese Female Undergraduate Students.

INTRODUCTION The influence of obesity on cardio-respiratory efficiency in the various phases of menstrual cycle is not well understood until now. As majority of Indian women have a favourable attitude towards participation in sports it is significant to understand the variation in exercise performance during different phases of menstrual cycle to have an optimum performance. AIM To evaluate the endurance capacity and cardio-respiratory responses in normal, obese and overweight female undergraduate students during different phases of menstrual cycle. MATERIALS AND METHODS Twenty normal weight, 20 obese and 20 over weight, unmarried, undergraduate female volunteers between the age group of 18-22 years, were recruited by convenient sampling. Cardio-respiratory efficiency was assessed by cardiac efficiency test, respiratory endurance test and respiratory blast test. RESULTS Overall, exercise efficiency varied significantly during the different phases of the menstrual cycle with the highest during luteal phase and lowest during menstrual phase. Similar trend was observed in all the three weight sub-categories, but it was statistically significant in the normal and overweight category only. There was no significant difference in blast test during menstrual phase, follicular phase and luteal phase of menstrual cycle among three groups of individuals. Overall the obese and overweight females had a decreased value for blast test compared to the normal individuals. Significant difference was observed in endurance test among follicular and luteal phase of normal females but there is no change in overweight and obese. Significant difference was observed in Peak Expiratory Flow Rate (PEFR) among luteal phase in normal and overweight individuals but there is no change in obese females. Overall obese individuals have a significant low PEFR compared to normal and overweight individuals. CONCLUSION Significant increase in cardiac and respiratory efficiency was observed in the luteal phase of the menstrual cycle in normal weight where as in overweight and obese females, there is an overall decrease in fitness capacity with increase in the Body Mass Index (BMI). Therefore, practice of regular exercise and intake of healthy diet which help in reducing the weight and in turn the BMI will help in enhancing the physical fitness of the individuals.
Assessing the Quality of Randomized Controlled Trials: Current Issues and Future Directions

Abstract Assessing the quality of randomized controlled trials is a relatively new and important development. Three approaches have been developed: component, checklist, and scale assessment. Component approaches evaluate selected aspects of trials, such as masking. Checklists and scales involve lists of items thought to be integral to study quality. Scales, unlike the other methods, provide a summary numeric score of quality, which can be formally incorporated into a systematic review. Most scales to date have not been developed with sufficient rigor, however. Empirical evidence indicates that differences in scale development can lead to important differences in quality assessment. Several methods for including quality scores in systematic reviews have been proposed, but since little empirical evidence supports any given method, results must be interpreted cautiously. Future efforts may be best focused on gathering more empirical evidence to identify trial characteristics directly related to bias in the estimates of intervention effects and on improving the way in which trials are reported.
Ontology versus terminology, from the perspective of ontologists

According to research teams’ experiments in ontology engineering field, building ontologies is much more time-consuming and costly than building terminologies with regard to ontology complexity and formality, two major differences between these types of resources. In the meantime, there are already many consensual terminologies for numerous knowledge domains available on the web, consequently these knowledge representations can constitute a great contribution in saving time and money in ontology building process field since terminologies can be considered as preliminary attempts to model particular domains by their respective experts. Though before performing such a reuse, it is essential to distinguish clearly which type of resource we are dealing with and therefore decide for its suitability for our purposes or not. This paper will focus on two leading points: on the one hand, a comparison between ontology and terminology on the basis of several features such as: basic principles, methodological aspects.