Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of immunohistochemistry in diagnosing renal neoplasms: when is it really useful?

CONTEXT With the refinement of molecular and histologic classifications of renal neoplasms and the availability of more-effective molecular targeted therapy for specific renal neoplasms, immunohistochemical techniques will play an increasingly important role in the diagnosis of renal neoplasm. During the past few decades, many markers have been evaluated for their role in the diagnosis, prognosis, and prediction of treatment for renal neoplasms. The number of useful markers in our routine practice continues to increase. The challenge will be to choose among them and to decide in which situations immunohistochemistry will be truly useful. OBJECTIVES To review the diagnostic utility of molecular markers for renal neoplasms and common diagnostic scenarios that call for immunohistochemistry in routine practice. DATA SOURCES This review is based on published literature and personal experience. CONCLUSIONS Some of the most important and useful markers for the diagnosis of renal neoplasm include cytokeratins, vimentin, PAX2, PAX8, RCC marker, CD10, E-cadherin, kidney-specific cadherin, parvalbumin, claudin-7, claudin-8, α-methylacyl coenzyme A racemase, CD117, TFE3, thrombomodulin, uroplakin III, p63, CD57, and carbonic anhydrase IX. Each marker has its diagnostic role in a specific diagnostic setting. The common diagnostic situations that call for immunohistochemical staining are differential diagnoses of renal versus nonrenal neoplasms, histologic subtyping of renal cell carcinoma, diagnosis of rare primary renal neoplasms, diagnosis of renal neoplasms in small core-biopsy specimens, diagnosis of possible metastatic renal carcinomas, and less frequently, molecular prognostication.
Randomized, double-blind, placebo-controlled clinical trial of the efficacy of treatment with zinc or vitamin A in infants and young children with severe acute lower respiratory infection.

BACKGROUND Acute lower respiratory infection (ALRI) is a leading cause of childhood death. Zinc supplementation prevents ALRI. Vitamin A supplementation reduces childhood mortality, but its benefit concerning ALRI-specific mortality is unproven. OBJECTIVE The objective was to evaluate the effect of zinc and vitamin A on the clinical recovery of children with severe ALRI. DESIGN In a controlled trial with a factorial design, 153 children aged 2-24 mo who were hospitalized with severe ALRI were randomly assigned to receive 10 mg zinc as acetate (twice daily for 5 d) plus vitamin A placebo, 10 000 micro g retinol equivalents vitamin A (twice daily for 4 d) plus zinc placebo, zinc plus vitamin A, or zinc and vitamin A placebos. The main outcome variable was the time for resolution of very ill status; other outcomes were resolution of fever, tachypnea, and feeding difficulty. RESULTS Recovery rates from very ill status and from fever in zinc-treated boys were 2.6 times (P = 0.004) and 3 times (P = 0.003) those in non-zinc-treated children; feeding difficulty and tachypnea were not significantly different between groups after an adjusted analysis. Recovery rates were not significantly different between groups on the basis of vitamin A treatment. At discharge, serum zinc was 6.06 micro mol/L higher (P = 0.001) in the zinc-treated children, and serum retinol was 0.387 micro mol/L higher (P = 0.001) in the vitamin A-treated children. CONCLUSION Zinc treatment significantly reduces duration of fever and very ill status in boys, but not in girls, with severe ALRI. Vitamin A treatment of children with severe ALRI had no significant beneficial effect.
Influence of the PVD and CVD technologies on the residual macro- stresses and functional properties of the coated tool ceramics

Purpose: The goal of this work is to compare the macro-stresses as well as mechanical and functional properties of the PVD and CVD coatings deposited on oxide and nitride ceramics tool. Design/methodology/approach: In the paper the residual macro-stresses of PVD and CVD coatings deposited on tool ceramics substrates, measured with the application of the grazing angle X-ray diffraction geometry are compared in relation to the fundamental mechanical properties like hardness and adhesion. Findings: Basing on the tribological test made by the use of the „pin-on-disk” method, the influence of the residual macro-stresses to wear resistance is being investigated. Practical implications: The process of covering tools with the thin wear resistant PVD and CVD coatings is currently the most commonly method used to extend their life. Investigations of those coatings determining their mechanical properties, chemical composition, and structure, enable to pick out the optimum coatings for given industrial applications. Originality/value: New X-ray diffraction g-sin2ψ method based on glancing angle X-ray beam geometry (GID), macro-stresses of the examined CVD and PVD coatings have been measured.
The use of angiogenic factors in discriminating preeclampsia: are they ready for prime time?

Objectives. We sought to evaluate the association between soluble fms-like tyrosine kinase 1 (sFlt1) and endoglin (ENG) and preeclampsia in an urban population, to develop a discriminatory model, and evaluate the association of these biomarkers with small for gestational age (SGA). Methods. Cases are prospectively identified with preeclampsia. Controls are term patients without preeclampsia. Commercially available ELISAs were used to measure levels of sFlt1, ENG, and placental growth factor (PlGF). Log-transformed levels were compared and multivariable logistic regression analyses were performed to control for confounders. Receiver operating characteristic curves were developed. Results. In cases (n = 86) compared to controls (n = 288), sFlt1 (p = 0.24) levels were no different. However, ENG levels were higher (p < 0.001), and PlGF levels were lower (p < 0.001). Further, levels of sFlt1 had poor discriminatory ability between cases and controls [AUC = 0.56, (0.48–0.63)]. The best model to discriminate between groups included clinical risk factors, ENG, and PlGF [AUC = 0.89, (0.85–0.92)]. Conclusions. Unlike recent reports, this study suggests that sFlt1 may have limited diagnostic utility in predicting preeclampsia, especially term disease.
Associations of Musculoskeletal Pain With Mobility in Older Adults: Potential Cerebral Mechanisms

Background Musculoskeletal pain is highly prevalent and limits mobility in older adults. A potential mechanism by which pain affects mobility could be through its negative impact on the brain. We examined whether structural integrity of cerebral gray and white matter (WM) mediated the relationship between pain and mobility in community-dwelling older adults. Methods Musculoskeletal pain, gait speed, and neuroimaging data were obtained concurrently from the Health ABC study (mean age = 83/56% female, n = 212). Microstructural gray matter integrity was measured by mean diffusivity (MD), WM microstructure and macrostructure were measured by fractional anisotropy (FA) and WM hyperintensities (WMH), respectively. Regression models were adjusted for gray matter atrophy, age, gender, medication use, and obesity. Bootstrapped mediation methods were used (1,000 bootstrapped samples, 95% confidence intervals). Results The associations of musculoskeletal pain with WMH (β = .19, p < .05) and FA (β = -.18, p < .05) were robust to adjustment for gender, medication use, age, body mass index (BMI), and brain atrophy. Participants who experienced both knee and back pain had a significantly slower gait speed (~0.11 m/s) than those without knee or back pain (p < .05) independent of gender, medication, age, and BMI. WMH and FA significantly mediated the pain-gait speed relationship. Associations between pain and MD were not significant, and MD did not modify the association between pain and gait speed. Conclusions Cerebral WM integrity may contribute to the detrimental effects of musculoskeletal pain on mobility, although pre-existing WM integrity may also simultaneously amplify pain and decrease mobility. Future studies are needed to further understand whether successful pain management may significantly improve both brain health and mobility.
A comparison of imputation methods in a longitudinal randomized clinical trial

It is common for longitudinal clinical trials to face problems of item non‐response, unit non‐response, and drop‐out. In this paper, we compare two alternative methods of handling multivariate incomplete data across a baseline assessment and three follow‐up time points in a multi‐centre randomized controlled trial of a disease management programme for late‐life depression. One approach combines hot‐deck (HD) multiple imputation using a predictive mean matching method for item non‐response and the approximate Bayesian bootstrap for unit non‐response. A second method is based on a multivariate normal (MVN) model using PROC MI in SAS software V8.2. These two methods are contrasted with a last observation carried forward (LOCF) technique and available‐case (AC) analysis in a simulation study where replicate analyses are performed on subsets of the originally complete cases. Missing‐data patterns were simulated to be consistent with missing‐data patterns found in the originally incomplete cases, and observed complete data means were taken to be the targets of estimation. Not surprisingly, the LOCF and AC methods had poor coverage properties for many of the variables evaluated. Multiple imputation under the MVN model performed well for most variables but produced less than nominal coverage for variables with highly skewed distributions. The HD method consistently produced close to nominal coverage, with interval widths that were roughly 7 per cent larger on average than those produced from the MVN model. Copyright © 2005 John Wiley & Sons, Ltd.
Genetic Ablation of Extra Domain A of Fibronectin in Hypercholesterolemic Mice Improves Stroke Outcome by Reducing Thrombo-Inflammation

Background— The fibronectin-splicing variant containing extra domain A (Fn-EDA) is present in negligible amounts in the plasma of healthy humans but markedly elevated in patients with comorbid conditions, including diabetes mellitus and hypercholesterolemia, which are risk factors for stroke. It remains unknown, however, whether Fn-EDA worsens stroke outcomes in such conditions. We determined the role of Fn-EDA in stroke outcome in a model of hypercholesterolemia, the apolipoprotein E–deficient (Apoe−/−) mouse. Methods and Results— In a transient cerebral ischemia/reperfusion injury model, Apoe−/− mice expressing fibronectin deficient in EDA (Fn-EDA−/−Apoe−/− mice) exhibited smaller infarcts and improved neurological outcomes at days 1 and 8 (P<0.05 versus Apoe−/− mice). Concomitantly, intracerebral thrombosis [assessed by fibrin(ogen) deposition] and postischemic inflammation (phospho–nuclear factor-&kgr;B p65, phospho–I&kgr;B kinase &agr;/&bgr;, interleukin 1&bgr;, and tumor necrosis factor-&agr;) within lesions of Fn-EDA−/−Apoe−/− mice were markedly decreased (P<0.05 versus Apoe−/− mice). In an FeCl3 injury–induced carotid artery thrombosis model, thrombus growth rate and the time to occlusion were prolonged in Fn-EDA−/−Apoe−/− mice (P<0.05 versus Apoe−/− mice). Genetic ablation of TLR4 improved stroke outcome in Apoe−/− mice (P<0.05) but had no effect on stroke outcome in Fn-EDA−/−Apoe−/− mice. Bone marrow transplantation experiments revealed that nonhematopoietic cell–derived Fn-EDA exacerbates stroke through Toll-like receptor-4 expressed on hematopoietic cells. Infusion of a specific inhibitor of Fn-EDA into Apoe−/− mouse 15 minutes after reperfusion significantly improved stroke outcome. Conclusions— Hypercholesterolemic mice deficient in Fn-EDA exhibit reduced cerebral thrombosis and less inflammatory response after ischemia/reperfusion injury. These findings suggest that targeting Fn-EDA could be an effective therapeutic strategy in stroke associated with hypercholesterolemia.
Molecular structure of cytoplasmic dynein 2 and its distribution in neuronal and ciliated cells

Cytoplasmic dynein is involved in a wide variety of cellular functions. In addition to the initially characterized form (MAP 1C/dynein 1), a second form of cytoplasmic dynein (dynein 2) has been identified and implicated in intraflagellar transport (IFT) in lower eukaryotes and in Golgi organization in vertebrates. In the current study, the primary structure of the full-length dynein 2 heavy chain (HC) was determined from cDNA sequence. The dynein 1 and dynein 2 sequences were similar within the motor region, and around the light intermediate chain (LIC)-binding site within the N-terminal stem region. The dynein 2 HC co-immunoprecipitated with LIC3, a homologue of dynein 1 LICs. Dynein 2 mRNA was abundant in the ependymal layer of the neural tube and in the olfactory epithelium. Antibodies to dynein 2 HC, LIC3 and a component of IFT particles strongly stained the ependymal layer lining the lateral ventricles. Both dynein 2 HC and LIC3 staining was also observed associated with connecting cilia in the retina and within primary cilia of non-neuronal cultured cells. These data support a specific role for dynein 2 in the generation and maintenance of cilia.
Single nucleotide editing without DNA cleavage using CRISPR/Cas9‐deaminase in the sea urchin embryo

Background: A single base pair mutation in the genome can result in many congenital disorders in humans. The recent gene editing approach using CRISPR/Cas9 has rapidly become a powerful tool to replicate or repair such mutations in the genome. These approaches rely on cleaving DNA, while presenting unexpected risks. Results: In this study, we demonstrate a modified CRISPR/Cas9 system fused to cytosine deaminase (Cas9‐DA), which induces a single nucleotide conversion in the genome. Cas9‐DA was introduced into sea urchin eggs with sgRNAs targeted for SpAlx1, SpDsh, or SpPks, each of which is critical for skeletogenesis, embryonic axis formation, or pigment formation, respectively. We found that both Cas9 and Cas9‐DA edit the genome, and cause predicted phenotypic changes at a similar efficiency. Cas9, however, resulted in significant deletions in the genome centered on the gRNA target sequence, whereas Cas9‐DA resulted in single or double nucleotide editing of C to T conversions within the gRNA target sequence. Conclusions: These results suggest that the Cas9‐DA approach may be useful for manipulating gene activity with decreased risks of genomic aberrations. Developmental Dynamics 246:1036–1046, 2017. © 2017 Wiley Periodicals, Inc.
Basal metabolism of weight-stable chronically undernourished men and women: lack of metabolic adaptation and ethnic differences.

The purpose of this study was to investigate whether weight-stable chronically energy-deficient subjects exhibit evidence of metabolic adaptation and to establish whether international predictive equations overestimate the basal metabolic rate (BMR) of tropical populations. BMR, body weight, height, and fat-free mass (FFM) by underwater weighing were measured in healthy, physically active urban dwellers of low socioeconomic status (178 men and women aged 22-38 y) in Bangalore, Southern India. Subjects were selected on the basis of body mass index (BMI; in kg/m2) and classified in three groups: severely undernourished (BMI < 17.0; n = 30 men, n = 25 women), marginally undernourished (BMI = 17.0-18.5; n = 31 men, n = 30 women), and well nourished (BMI > 18.5; n = 27 men, n = 35 women). The BMR of the well-nourished group, expressed in absolute terms (6.20 and 5.18 MJ/d for men and women, respectively), was significantly higher (P < 0.000) than that of the severely undernourished group (5.72 and 4.64 MJ/d for men and women, respectively). Normalizing BMR for either body weight or FFM by analysis of covariance abolished all differences. The mean BMR of the low-BMI study group was substantially higher (11-14%) than reported previously for undernourished Indian adults. The BMR of both men and women, regardless of their nutritional status, was accurately estimated by age- and sex-specific FAO/WHO/UNU equations. These findings suggest the absence of an enhanced metabolic response in weight-stable chronically undernourished adults. This is in contrast with earlier reports, and supports more recent views. The study also provides evidence of the absence of ethnic-specific energy turnover in Indians.
Spatial Variation in the Selective Scenarios of Hormathophylla spinosa (Cruciferae)

The effects of multispecific systems containing both mutualistic and antagonistic interacting organisms on the evolution of plant traits have seldom been analyzed. We studied the selection exerted by several species of herbivores and pollinators in three populations of Hormathophylla spinosa (Cruciferae) in the Sierra Nevada (Spain) over 4 yr by using path analyses and structural equation modeling (SEM). The main selective pressures in our study sites were ungulates and pollinators. However, the importance of each kind of interacting organism differed among populations. Our results indicate a selection mosaic among populations of H. spinosa in the Sierra Nevada caused by the spatial variation in the relative importance of different interactions as selective pressures. We found two main selective scenarios, depending on the presence or absence of ungulates. In the populations with low ungulate pressure, there was positive phenotypic selection in flower number per plant and in flower density (mediated by nectarivorous pollinators). In the two populations with high ungulate pressure, there was a strong positive, ungulate‐mediated selection in thorn density. Our results suggest that the application of SEM to several populations simultaneously monitored might help to isolate the major selection pressures on local populations and identify potential differences in selection among populations, becoming a useful exploratory approach to study the geographical variation of selection in complex systems.
A General and Dynamic Species Abundance Model, Embracing the Lognormal and the Gamma Models

One aspect of community ecology that has been given particular attention is the pattern of species abundances in a community. The species may have a wide range of abundances; some are very common and others rare. When species abundance models are fitted to observations, the lognormal model and one of the gamma models (e.g., the log‐series model) are usually applied. The model that gives the best fit according to some goodness‐of‐fit test is then chosen. By applying a diffusion approximation for each species’ dynamics with density regulation of the θ‐logistic type, we here present a general species abundance model that embraces the two most widely applied species abundance models, the lognormal and the gamma. Our general model will, therefore, provide a better fit than the two special cases, except when it corresponds to one of them. In contrast to the classical models, ours is also dynamic, making it possible to evaluate the fluctuations in species abundance over time through both biotic and abiotic factors. The model is fitted to several species abundance data sets and our results compared to previous attempts to fit a model, usually either the lognormal or the log‐series.
Sensitivity Analysis for Mirror-Stratifiable Convex Functions

This paper provides a set of sensitivity analysis and activity identification results for a class of convex functions with a strong geometric structure, that we coined "mirror-stratifiable". These functions are such that there is a bijection between a primal and a dual stratification of the space into partitioning sets, called strata. This pairing is crucial to track the strata that are identifiable by solutions of parametrized optimization problems or by iterates of optimization algorithms. This class of functions encompasses all regularizers routinely used in signal and image processing, machine learning, and statistics. We show that this "mirror-stratifiable" structure enjoys a nice sensitivity theory, allowing us to study stability of solutions of optimization problems to small perturbations, as well as activity identification of first-order proximal splitting-type algorithms. Existing results in the literature typically assume that, under a non-degeneracy condition, the active set associated to a minimizer is stable to small perturbations and is identified in finite time by optimization schemes. In contrast, our results do not require any non-degeneracy assumption: in consequence, the optimal active set is not necessarily stable anymore, but we are able to track precisely the set of identifiable strata.We show that these results have crucial implications when solving challenging ill-posed inverse problems via regularization, a typical scenario where the non-degeneracy condition is not fulfilled. Our theoretical results, illustrated by numerical simulations, allow to characterize the instability behaviour of the regularized solutions, by locating the set of all low-dimensional strata that can be potentially identified by these solutions.
Infant nutrition and blood pressure in early adulthood: the Barry Caerphilly Growth study.

BACKGROUND Evidence suggests that environmental factors acting early in life may affect blood pressure in adulthood. OBJECTIVE The objective was to test the hypothesis that dried formula milk (derived from cow milk) intake in infancy is positively associated with blood pressure in early adulthood. DESIGN We conducted a long-term follow-up (1997-1999) of the Barry Caerphilly Growth study cohort (1972-1974) into which mothers and their offspring had originally been randomly assigned to receive a milk supplement or usual care. Participants were the offspring, who were aged 23-27 y at follow-up. The main outcome measures were systolic and diastolic blood pressure. RESULTS The social and demographic characteristics of the subjects who were (n = 679) and were not (n = 272) followed up were similar. For each increase in quartile of dried milk consumption (in oz) at 3 mo of age, there was a 1.28-mm Hg (95% CI: 0.46, 2.10 mm Hg) increase in systolic and a 0.63-mm Hg (95% CI: 0.04, 1.22 mm Hg) increase in diastolic blood pressure after adjustment for sex, intervention group, birth weight z scores, social class in childhood, age at follow-up, alcohol consumption, and pack-years of smoking. These coefficients were attenuated when adult body mass index and height were included in the models, but the association of dried milk consumption at 3 mo of age with systolic pressure remained significant (1.07 mm Hg; 95% CI: 0.27, 1.87 mm Hg). CONCLUSIONS Our findings are consistent with the hypothesis that high blood pressure in later life is influenced by early postnatal nutrition. Thus, interventions to optimize infant nutrition may have important long-term health benefits.