Miracle-dz/UniFAR-FTUs huggingface dataset:
Emerging critical role of molecular testing in diagnostic genitourinary pathology.

CONTEXT The unprecedented advances in cancer genetics and genomics are rapidly affecting clinical management and diagnostics in solid tumor oncology. Molecular diagnostics is now an integral part of routine clinical management in patients with lung, colon, and breast cancer. In sharp contrast, molecular biomarkers have been largely excluded from current management algorithms of urologic malignancies. OBJECTIVE To discuss promising candidate biomarkers that may soon make their transition to the realm of clinical management of genitourologic malignancies. The need for new treatment alternatives that can improve upon the modest outcome so far in patients with several types of urologic cancer is evident. Well-validated prognostic molecular biomarkers that can help clinicians identify patients in need of early aggressive management are lacking. Identifying robust predictive biomarkers that will stratify response to emerging targeted therapeutics is another crucially needed development. A compiled review of salient studies addressing the topic could be helpful in focusing future efforts. DATA SOURCES A PubMed (US National Library of Medicine) search for published studies with the following search terms was conducted: molecular , prognostic , targeted therapy , genomics , theranostics and urinary bladder cancer , prostate adenocarcinoma , and renal cell carcinoma . Articles with large cohorts and multivariate analyses were given preference. CONCLUSIONS Our recent understanding of the complex molecular alterations involved in the development and progression of urologic malignancies is yielding novel diagnostic and prognostic molecular tools and opening the doors for experimental targeted therapies for these prevalent, frequently lethal solid tumors.
Cellular and intercellular transport pathways in exchange vessels.

The endothelium of lung alveolar capillaries is of the continuous type, that of airway exchange vessels (capillaries and pericytic venules) includes both continuous and fenestrated types. Water and small lipophilic solutes penetrate via the endothelial cells (cell membrane pathway) as well as through intercellular junctions. Hydrophilic solutes are limited to junctional pathways and cytoplasmic vesicles. Permeation of hydrophilic solutes is progressively restricted with increasing molecular size, as by a sieve, with many openings 8 nm and a few 40 to 60 nm wide. In response to local tissue injury or to certain chemical mediators, larger junctional pathways may be opened, greatly increasing permeability to large molecules. Both alveolar capillaries and airway exchange vessels exhibit this response, but the effective stimuli may differ (e.g., alveolar capillaries are insensitive to histamine and bradykinin). Hydrophilic solutes are transported by diffusion, convection, and vesicular exchange (transcytosis). For small ions and molecules (radii < 2 nm), diffusion is the dominant transport mode; contributions of convection and transcytosis are negligibly small. Because diffusion decreases with increasing molecular size, all three mechanisms may contribute substantially to transport of large molecules (radii > 2 nm). Fenestrated endothelia have higher hydraulic conductivities and are more permeable to small ions and molecules than are continuous endothelia. However, their permeabilities to plasma proteins are about the same. Lung alveolar capillary endothelium has lower hydraulic conductivity and lower solute permeabilities than do other continuous endothelia (heart, skeletal muscle). Airway exchange vessel endothelium has about the same permeability to serum albumin as alveolar capillary endothelium.
Factors Associated with the Referral of Anxious Children to Mental Health Care: the Influence of Family Functioning, Parenting, Parental Anxiety and Child Impairment

This study aims to identify factors that predict the mental health care referral of anxious children. In total, 249 children and families, aged 8–13 years, participated: 73 children were referred with anxiety disorders to mental health care [mean (M) age =10.28, standard deviation (SD) =1.35], 176 non‐referred anxious children recruited in primary schools (M age =9.94, SD =1.22). Child anxiety and other disorders were assessed with semi‐structured interviews. Child anxiety symptoms, behavioural problems, parental anxiety, the parenting styles overprotection, autonomy encouragement, rejection, and the family functioning dimensions control and relational functioning, were assessed with child, father and mother report on questionnaires. The summed interference rating of children's anxiety disorders was a predictor of referral, consistent over child and parent reports, but not comorbidity. Most family and parenting variables did not predict referral, nor differed between the referred and non‐referred sample. Contrary to our hypothesis, maternal self‐reported anxiety decreased the odds of referral and child reported parental autonomy granting increased, while child reported overprotection decreased the odds of referral. The impairment for the child due to the number and severity of their anxiety disorder(s) is, based on child, mother and father report associated with referral. This indicates that those who need it most, receive clinical treatment. Copyright © 2014 John Wiley & Sons, Ltd.
Oscillating migration and the epidemics of silicosis, tuberculosis, and HIV infection in South African gold miners.

BACKGROUND Hundreds of thousands of men from rural areas of South Africa and neighboring countries have come to seek work in the gold mines. They are not immigrants in the usual sense as they work for periods in the mines, go home, and then return. This is termed oscillating or circular migration. Today we have serious interrelated epidemics of silicosis, tuberculosis, and HIV infection in the gold mining industry. METHODS This article discusses the role of oscillating migration in fuelling these epidemics, by examining the historical, political, social, and economic contexts of these diseases. RESULTS The impact of silicosis, tuberculosis, and HIV infection extends beyond individual miners to their families and communities. CONCLUSION Failure to control dust and tuberculosis has resulted in serious consequences decades later. The economic and political migrant labor system provided the foundations for the epidemics seen in southern Africa today.
User interactions in social networks and their implications

Social networks are popular platforms for interaction, communication and collaboration between friends. Researchers have recently proposed an emerging class of applications that leverage relationships from social networks to improve security and performance in applications such as email, web browsing and overlay routing. While these applications often cite social network connectivity statistics to support their designs, researchers in psychology and sociology have repeatedly cast doubt on the practice of inferring meaningful relationships from social network connections alone. This leads to the question: Are social links valid indicators of real user interaction? If not, then how can we quantify these factors to form a more accurate model for evaluating socially-enhanced applications? In this paper, we address this question through a detailed study of user interactions in the Facebook social network. We propose the use of interaction graphs to impart meaning to online social links by quantifying user interactions. We analyze interaction graphs derived from Facebook user traces and show that they exhibit significantly lower levels of the "small-world" properties shown in their social graph counterparts. This means that these graphs have fewer "supernodes" with extremely high degree, and overall network diameter increases significantly as a result. To quantify the impact of our observations, we use both types of graphs to validate two well-known social-based applications (RE and SybilGuard). The results reveal new insights into both systems, and confirm our hypothesis that studies of social applications should use real indicators of user interactions in lieu of social graphs.
The coefficient of error of optical fractionator population size estimates: a computer simulation comparing three estimators

The optical fractionator is a design‐based two‐stage systematic sampling method that is used to estimate the number of cells in a specified region of an organ when the population is too large to count exhaustively. The fractionator counts the cells found in optical disectors that have been systematically sampled in serial sections. Heretofore, evaluations of optical fractionator performance have been made by performing tests on actual tissue sections, but it is difficult to evaluate the coefficient of error (CE), i.e. the precision of a population size estimate, by using biological tissue samples because they do not permit a comparison of an estimated CE with the true CE. However, computer simulation does permit making such comparisons while avoiding the observational biases inherent in working with biological tissue.
Cyclic Nucleotide Phosphodiesterase 1 Regulates Lysosome-Dependent Type I Collagen Protein Degradation in Vascular Smooth Muscle Cells

Objective—The phenotypic modulation of vascular smooth muscle cells (VSMCs) to a synthetic phenotype is vital during pathological vascular remodeling and the development of various vascular diseases. An increase in type I collagen (collagen I) has been implicated in synthetic VSMCs, and cyclic nucleotide signaling is critical in collagen I regulation. Herein, we investigate the role and underlying mechanism of cyclic nucleotide phosphodiesterase 1 (PDE1) in regulating collagen I in synthetic VSMCs. Methods and Results—The PDE1 inhibitor IC86340 significantly reduced collagen I in human saphenous vein explants undergoing spontaneous remodeling via ex vivo culture. In synthetic VSMCs, high basal levels of intracellular and extracellular collagen I protein were markedly decreased by IC86340. This attenuation was due to diminished protein but not mRNA. Inhibition of lysosome function abolished the effect of IC86340 on collagen I protein expression. PDE1C but not PDE1A is the major isoform responsible for mediating the effects of IC86340. Bicarbonate-sensitive soluble adenylyl cyclase/cAMP signaling was modulated by PDE1C, which is critical in collagen I degradation in VSMCs. Conclusion—These data demonstrate that PDE1C regulates soluble adenylyl cyclase/cAMP signaling and lysosome-mediated collagen I protein degradation, and they suggest that PDE1C plays a critical role in regulating collagen homeostasis during pathological vascular remodeling.
Opioid Receptor Homo- and Heterodimerization in Living Cells by Quantitative Bioluminescence Resonance Energy Transfer

Opioid receptors have been shown to dimerize or oligomerize among themselves and each other, affecting their functional properties. This study used bioluminescence resonance energy transfer (BRET) between the μ, δ, and κ opioid receptors to study opioid receptor aggregation in transfected human embryonic kidney 293 cells. Titration of receptor levels indicated that all three opioid receptors have a similar affinity to form homo- or hetero-oligomers in combination with any other opioid receptor type. In contrast, none of the opioid receptors formed detectable oligomers with the muscarinic M2 receptor, indicating that interactions among opioid receptors are selective. The formation of opioid receptor dimers, rather than higher order oligomers, is supported by binding kinetics in competition experiments between labeled and unlabeled receptors. Opioid receptor dimerization occurred at physiological temperatures upon receptor biosynthesis, before trafficking to the plasma membrane. Moreover, using BRET, coimmunoprecipitation, receptor binding, and G protein coupling, we demonstrate for the first time functional μ opioid receptor-κ opioid receptor heterodimerization. These combined results demonstrate that opioid receptors can undergo homo- and heterodimerization, a process with potential implications for opioid physiology and pharmacology.
Multiple Kernel Learning Algorithms

In recent years, several methods have been proposed to combine multiple kernels instead of using a single one. These different kernels may correspond to using different notions of similarity or may be using information coming from multiple sources (different representations or different feature subsets). In trying to organize and highlight the similarities and differences between them, we give a taxonomy of and review several multiple kernel learning algorithms. We perform experiments on real data sets for better illustration and comparison of existing algorithms. We see that though there may not be large differences in terms of accuracy, there is difference between them in complexity as given by the number of stored support vectors, the sparsity of the solution as given by the number of used kernels, and training time complexity. We see that overall, using multiple kernels instead of a single one is useful and believe that combining kernels in a nonlinear or data-dependent way seems more promising than linear combination in fusing information provided by simple linear kernels, whereas linear methods are more reasonable when combining complex Gaussian kernels.
Effects of Chemotherapy in Breast Cancer Patients

Introduction: A descriptive, non-interventional study was conducted from April 2011 to September 2013, at KIRAN hospital, Karachi among n = 811 female breast cancer patients to assess the effects of chemotherapeutic agents that were employed for the treatment of breast cancer. The assessment was done so as to see the variation in response of the patients towards the drugs used specifically the adverse effects that have to be combated during therapy. Methodology: During 3-6 months, a follow up was done to collect data for ADEs (Adverse Drug Events) that occurred among patients after therapy. The SPSS version 16.0 was used for statistical analysis of the data. The adverse events that occurred due to adjuvant chemotherapy including severity, preventability and causality were evaluated using three International scales i.e. Modified Schumock and Thornton scale, modified Hartwig’s and Siegal’s scale and Naranjo’s algorithm. Results and Discussion: Majority of the patients received 6 cycles of FAC therapy (5-fluorouracil, Adriamycin/doxorubicin, cyclophosphamide) and showed good response. The assessment of ADRs using different scales revealed hair loss, nausea, vomiting, anemia and neutropenia as the non-preventable definite effects that were experienced by the patients. Mild to moderate diarrhea/constipation was probably preventable and hence doubtful. Moderately probable effects included mucositis and mouth ulcers whereas possible effects included fever and chills. Conclusion: Through the right use of medicines, the mild effect of headache and pain could be certainly preventable. Hence chemotherapeutic agents must be chosen for each patient on individual basis to prevent or lessen the toxic effects rendered to them and be useful in the disease course.
FASTER: an unsupervised fully automated sleep staging method for mice

Identifying the stages of sleep, or sleep staging, is an unavoidable step in sleep research and typically requires visual inspection of electroencephalography (EEG) and electromyography (EMG) data. Currently, scoring is slow, biased and prone to error by humans and thus is the most important bottleneck for large‐scale sleep research in animals. We have developed an unsupervised, fully automated sleep staging method for mice that allows less subjective and high‐throughput evaluation of sleep. Fully Automated Sleep sTaging method via EEG/EMG Recordings (FASTER) is based on nonparametric density estimation clustering of comprehensive EEG/EMG power spectra. FASTER can accurately identify sleep patterns in mice that have been perturbed by drugs or by genetic modification of a clock gene. The overall accuracy is over 90% in every group. 24‐h data are staged by a laptop computer in 10 min, which is faster than an experienced human rater. Dramatically improving the sleep staging process in both quality and throughput FASTER will open the door to quantitative and comprehensive animal sleep research.
The importance of the body's need for zinc in determining Zn availability in food: a principle demonstrated in the rat

1. The hypothesis that the availability of zinc in a food is limited by factors in the food was tested against the hypothesis that Zn absorption is homeostatically regulated by the body according to its need for Zn. 2. The experimental model used was the short-term administration to rats of a parenteral nutrition solution with no added Zn in an attempt to increase their need for Zn in an anabolic phase. 3. The absorption and retention of 65Zn from a piece of endosperm-wheat crisp-bread in rats injected intraperitoneally with the parenteral nutrition solution was more than 40% higher than that in a control group injected with physiological saline (9 g sodium chloride/l). 4. The results indicate that the availability of Zn in the bread is not fixed but variable and dependent on the body's need for Zn.
Strategic regulation of cognitive control by emotional salience: A neural network model

We present a neural network model of stimulus processing, which uses a mechanism of adaptive attentional control to regulate the moment to moment deployment of attention according to both the demands of the current task, and the demands of emotionally salient information. This mechanism allows negative emotional information to reduce cognitive control to aid in the detection of threats, which produces a momentary withdrawal from the current task set to allow unbiased processing of available information. The combination of cognitive and emotional regulation of task set allows this model to address inter-trial aspects of emotional interference in colour naming. In particular, we focus on the nature of the emotional interference in colour naming (McKenna & Sharma, 2004) as well as in word reading (Algom, Chajut, & Lev, 2004) and show how this form of interference is functionally distinct from the classic Stroop effect. Our model addresses a range of findings in colour naming and word reading tasks and is informed by recent neuroimaging data concerning the interaction between the anterior cingulate and prefrontal cortices. The model is used to explore the interface between cognition and emotion with a series of predictions, including a qualitative distinction between state and trait forms of anxiety.
SIRT1 is a redox‐sensitive deacetylase that is post‐translationally modified by oxidants and carbonyl stress

Sirtuinl (SIRT1) deacetylase levels are decreased in chronic inflammatory conditions and aging where oxidative stress occurs. We determined the mechanism of SIRT1 redox post‐translational modifications leading to its degradation. Human lung epithelial cells exposed to hydrogen peroxide (150–250 µM), aldehyde‐acrolein (10–30 µM), and cigarette smoke extract (CSE;0.1–1.5%) in the presence of intracellular glutathione‐modulating agents at 1–24 h, and oxidative post‐translational modifications were assayed in cells, as well as in lungs of mice lacking and overexpressing glutaredoxin‐1 (Glrx1), and wild‐type (WT) mice in response to cigarette smoke (CS). CSE and aldehydes dose and time dependently decreased SIRT1 protein levels, with EC50 of 1% for CSE and 30 µM for acrolein at 6 h, and >80% inhibition at 24 h with CSE, which was regulated by modulation of intracellular thiol status of the cells. CS decreased the lung levels of SIRT1 in WT mice, which was enhanced by deficiency of Glrx1 and prevented by overexpression of Glrx1. Oxidants, aldehydes, and CS induced carbonyl modifications on SIRT1 on cysteine residues concomitant with decreased SIRT1 activity. Proteomics studies revealed alkylation of cysteine residue on SIRT1. Our data suggest that oxidants/aldehydes covalently modify SIRT1, decreasing enzymatic activity and marking the protein for proteasomal degradation, which has implications in inflammatory conditions. —Caito, S. , Rajendrasozhan, S. , Cook, S. , Chung, S. , Yao, H. , Friedman, A. E. , Brookes, P. S. , Rahman, I. SIRT1 is a redox‐sensitive deacetylase that is post‐translationally modified by oxidants and carbonyl stress. FASEB J. 24, 3145–3159 (2010). www.fasebj. org
Proteomics of Cancer Cell Lines Resistant to Microtubule-Stabilizing Agents

Despite the clinical success of microtubule-interacting agents (MIA), a significant challenge for oncologists is the inability to predict the response of individual patients with cancer to these drugs. In the present study, six cell lines were compared by 2D DIGE proteomics to investigate cellular resistance to the class of MIAs known as microtubule-stabilizing agents (MSA). The human lung cancer cell line A549 was compared with two drug-resistant daughter cell lines, a taxol-resistant cell line (AT12) and an epothilone B (EpoB)-resistant cell line (EpoB40). The ovarian cancer cell line Hey was compared with two drug-resistant daughter cell lines, an EpoB-resistant cell line (EpoB8) and an ixabepilone-resistant cell line (Ixab80). All 2D DIGE results were validated by Western blot analyses. A variety of cytoskeletal and cytoskeleton-associated proteins were differentially expressed in drug-resistant cells. Differential abundance of 14-3-3σ, galectin-1 and phosphorylation of stathmin are worthy of further studies as candidate predictive biomarkers for MSAs. This is especially true for galectin-1, a β-galactose–binding lectin that mediates tumor invasion and metastasis. Galectin-1 was greatly increased in EpoB- and ixabepilone-resistant cells and its suppression caused an increase in drug sensitivity in both drug-sensitive and -resistant Hey cells. Furthermore, the growth medium from resistant Hey cells contained higher levels of galectin-1, suggesting that galectin-1 could play a role in resistance to MSAs. Mol Cancer Ther; 13(1); 260–9. ©2013 AACR.
Subjective and objective measurements of postoperative pain in cats.

OBJECTIVE To evaluate the ability of various subjective and objective measurements to determine the presence and degree of postoperative pain in cats. DESIGN Randomized controlled prospective clinical study. ANIMALS 18 healthy client-owned cats. PROCEDURE Cats were randomly assigned to 3 groups of 6: control, tenectomy, and onychectomy. Jugular catheters were placed the day prior to surgery. All surgeries were performed by the same surgeon, and all observations were made by the same blinded trained observer. One hour prior to surgery and at assigned intervals for 36 hours after surgery, heart rate, respiratory rate, and rectal temperature were measured. Scores were assigned for 3 interaction responses, including response to palpation, by use of simple descriptive scales, and to 2 pain assessments by use of visual analogue scales. Blood was collected to measure plasma beta-endorphin and cortisol concentrations. Butorphanol was administered to all cats before surgery and to any cat subjectively assessed to be experiencing pain after surgery. RESULTS Only visual analogue scale scores and response to palpation scores differed significantly between control and surgical groups. CONCLUSIONS AND CLINICAL RELEVANCE Determination of the presence of pain in cats can be made on the basis of observation and interaction by a trained observer. Physiologic measurements, including plasma cortisol and beta-endorphin concentrations, did not differentiate between control cats and cats that underwent surgery.