Miracle-dz/UniFAR-FTUs huggingface dataset:
Selective Internal Radiation Therapy-induced Extrahepatic Injury: An Emerging Cause of Iatrogenic Organ Damage

Selective internal radiation therapy (SIRT) using 90Yttrium microspheres is a novel therapeutic approach to the localized treatment of hepatic tumors. It provides a distinct advantage over conventional external beam radiation in that its targeted nature allows the directed delivery of high doses of radiation to tumors while sparing the surrounding uninvolved hepatic parenchyma. Numerous studies have evaluated the safety and efficacy of SIRT, and it has been used to treat both primary and metastatic hepatic malignancies. However, SIRT is not without risk of complications, and has been known to cause various toxicities due to extrahepatic SIRT microsphere deposition. Reports of such injury have been only sparsely described in the pathology literature to date, and surgical pathologists therefore remain largely unaware of this phenomenon, which can potentially lead to misdiagnosis. Herein, we review the histopathology and pathophysiology of extrahepatic SIRT microsphere migration as a cause of iatrogenic tissue injury, highlighted by 3 examples of gastritis and 1 case of cholecystitis.
MOF and H4 K16 Acetylation Play Important Roles in DNA Damage Repair by Modulating Recruitment of DNA Damage Repair Protein Mdc1

ABSTRACT MOF (MYST1) is the major enzyme to catalyze acetylation of histone H4 lysine 16 (K16) and is highly conserved through evolution. Using a conditional knockout mouse model and the derived mouse embryonic fibroblast cell lines, we showed that loss of Mof led to a global reduction of H4 K16 acetylation, severe G2/M cell cycle arrest, massive chromosome aberration, and defects in ionizing radiation-induced DNA damage repair. We further showed that although early DNA damage sensing and signaling by ATM were normal in Mof-null cells, the recruitment of repair mediator protein Mdc1 and its downstream signaling proteins 53bp1 and Brca1 to DNA damage foci was completely abolished. Mechanistic studies suggested that Mof-mediated H4 K16 acetylation and an intact acidic pocket on H2A.X were essential for the recruitment of Mdc1. Removal of Mof and its associated proteins phenocopied a charge-neutralizing mutant of H2A.X. Given the well-characterized H4-H2A trans interactions in regulating higher-order chromatin structure, our study revealed a novel chromatin-based mechanism that regulates the DNA damage repair process.
Role of Cross Talk in Regulating the Dynamic Expression of the Flagellar Salmonella Pathogenicity Island 1 and Type 1 Fimbrial Genes

ABSTRACT Salmonella enterica, a common food-borne pathogen, differentially regulates the expression of multiple genes during the infection cycle. These genes encode systems related to motility, adhesion, invasion, and intestinal persistence. Key among them is a type three secretion system (T3SS) encoded within Salmonella pathogenicity island 1 (SPI1). In addition to the SPI1 T3SS, other systems, including flagella and type 1 fimbriae, have been implicated in Salmonella pathogenesis. In this study, we investigated the dynamic expression of the flagellar, SPI1, and type 1 fimbrial genes. We demonstrate that these genes are expressed in a temporal hierarchy, beginning with the flagellar genes, followed by the SPI1 genes, and ending with the type 1 fimbrial genes. This hierarchy could mirror the roles of these three systems during the infection cycle. As multiple studies have shown that extensive regulatory cross talk exists between these three systems, we also tested how removing different regulatory links between them affects gene expression dynamics. These results indicate that cross talk is critical for regulating gene expression during transitional phases in the gene expression hierarchy. In addition, we identified a novel regulatory link between flagellar and type 1 fimbrial gene expression dynamics, where we found that the flagellar regulator, FliZ, represses type 1 fimbrial gene expression through the posttranscriptional regulation of FimZ. The significance of these results is that they provide the first systematic study of the effect of regulatory cross talk on the expression dynamics of flagellar, SPI1, and type 1 fimbrial genes.
Network over‐connectivity differentiates autism spectrum disorder from other developmental disorders in toddlers: A diffusion MRI study

Advanced connectivity studies in toddlers with Autism Spectrum Disorder (ASD) are increasing and consistently reporting a disruption of brain connectivity. However, most of these studies compare ASD and typically developing subjects, thus providing little information on the specificity of the abnormalities detected in comparison with other developmental disorders (other‐DD). We recruited subjects aged below 36 months who received a clinical diagnosis of Neurodevelopmental Disorder (32 ASD and 16 other‐DD including intellectual disability and language disorder) according to DSM‐IV TR. Structural and diffusion MRI were acquired to perform whole brain probabilistic and anatomically constrained tractography. Network connectivity matrices were built encoding the number of streamlines (DNUM) and the tract‐averaged fractional anisotropy (DFA) values connecting each pair of cortical and subcortical regions. Network Based Statistics (NBS) was finally applied on the connectivity matrices to evaluate the network differences between the ASD and other‐DD groups. The network differences resulted in an over‐connectivity pattern (i.e., higher DNUM and DFA values) in the ASD group with a significance of P < 0.05. No contra‐comparison results were found. The over‐connectivity pattern in ASD occurred in networks primarily involving the fronto‐temporal nodes, known to be crucial for social‐skill development and basal ganglia, related to restricted and repetitive behaviours in ASD. To our knowledge, this is the first network‐based diffusion study comparing toddlers with ASD and those with other‐DD. Results indicate the detection of different connectivity patterns in ASD and other‐DD at an age when clinical differential diagnosis is often challenging. Hum Brain Mapp 38:2333–2344, 2017. © 2017 Wiley Periodicals, Inc.
Lean-seafood intake decreases urinary markers of mitochondrial lipid and energy metabolism in healthy subjects: Metabolomics results from a randomized crossover intervention study.

SCOPE Proteins constitute an important part of the human diet, but understanding of the effects of different dietary protein sources on human metabolism is sparse. We aimed to elucidate diet-induced metabolic changes through untargeted urinary metabolomics after four weeks of intervention with lean-seafood or nonseafood diets. It is shown that lean-seafood intake reduces urinary excretion of metabolites involved in mitochondrial lipid and energy metabolism possibly facilitating a higher lipid catabolism in healthy subjects. METHODS In a randomized controlled trial with crossover design, 20 healthy subjects consumed two balanced diets that varied in main protein sources for 4 weeks. Morning spot urine samples were collected before and after each intervention period. Untargeted metabolomics based on (1) H NMR spectroscopy and LC-MS analyses were applied to characterize the urinary metabolic response to the interventions. RESULTS The lean-seafood diet period reduced the urinary level of l-carnitine, 2,6-dimethylheptanoylcarnitine, and N-methyl-2-pyridone-5-carboxamide, relative to the nonseafood period. The dietary analysis revealed that the higher urinary level of trimethylamine-N-oxide after the lean-seafood diet period and guanidinoacetate and 3-methylhistidine after the nonseafood diet period was related to the endogenous content of these compounds in the diets. CONCLUSIONS Our data reveal that 4 weeks of lean-seafood intake reduces urinary excretion of metabolites involved in mitochondrial lipid and energy metabolism possibly facilitating a higher lipid catabolism in healthy subjects after the lean-seafood intake.
Identification of selection signatures in livestock species

The identification of regions that have undergone selection is one of the principal goals of theoretical and applied evolutionary genetics. Such studies can also provide information about the evolutionary processes involved in shaping genomes, as well as physical and functional information about genes/genomic regions. Domestication followed by breed formation and selection schemes has allowed the formation of very diverse livestock breeds adapted to a wide variety of environments and with special characteristics. The advances in genomics in the last five years have enabled the development of several methods to detect selection signatures and have resulted in the publication of a considerable number of studies involving livestock species. The aims of this review are to describe the principal effects of natural/artificial selection on livestock genomes, to present the main methods used to detect selection signatures and to discuss some recent results in this area. This review should be useful also to research scientists working with wild animals/non-domesticated species and plant biologists working with breeding and evolutionary biology.
Combined Cytomorphologic and Immunophenotypic Analysis in the Diagnostic Workup of Lymphomatous Effusions

OBJECTIVE To analyze the results of cytomorphology and immunophenotyping in 54 patients with lymphomatous effusions. STUDY DESIGN We report the results of cytomorphology and immunophenotyping in 54 patients with lymphomatous effusions. Twenty-three of the 54 had a previous diagnosis of NHL. In the remaining 31 patients, lymphomatous involvement was clinically suspected. RESULTS Thirty-three lymphomatous effusions were positive for involvement by NHL. Twenty-one of these 33 patients (64%) had a previous diagnosis of NHL. Of the remaining 12 patients with newly diagnosed NHL, 11 had high grade lymphoma, and one had follicular center lymphoma. Twenty effusions were considered to be reactive; only two of these patients had NHL. One effusion revealed involvement by a previously unknown carcinoma. We observed seven false negative results if only one of both methods was considered. A high grade NHL was not diagnosed by immunophenotyping in one case, and six cases of low grade NHL could not be detected by cytomorphology. The combined strategy of cytomorphology and immunophenotyping had a sensitivity of 100% and specificity of 100% in our study, confirmed by follow-up studies. CONCLUSION Both methods have shown difficulties in the examination of lymphomatous effusions. Cytomorphology has problems distinguishing reactive effusions from low grade NHL. The detection of high grade NHL by immunophenotyping is difficult. However, both methods together offer the advantage of dual staining ability and are most helpful in distinguishing clonal lymphomatous from reactive effusions.
Tugging at the Seams: Understanding the Fabric of Social Sites

Social networking websites have become increasingly popular in recent times, yet it can be difficult to understand the way in which people use these spaces. This poster presents a systematic deconstruction method which grants insight into the nature of a given experience, and shows how this knowledge can be used to reconstruct experiences in new contexts. The authors demonstrate the method by applying it to some key facets of social websites, and discuss how the functionality might be reconstructed in different contexts such as ubiquitous computing. We evaluate the method and discuss the findings, noting that if social material can be provided in new contexts, far more people can be included in interactions which are currently limited to the web.
Interventions over Predictions: Reframing the Ethical Debate for Actuarial Risk Assessment

Actuarial risk assessments might be unduly perceived as a neutral way to counteract implicit bias and increase the fairness of decisions made at almost every juncture of the criminal justice system, from pretrial release to sentencing, parole and probation. In recent times these assessments have come under increased scrutiny, as critics claim that the statistical techniques underlying them might reproduce existing patterns of discrimination and historical biases that are reflected in the data. Much of this debate is centered around competing notions of fairness and predictive accuracy, resting on the contested use of variables that act as "proxies" for characteristics legally protected against discrimination, such as race and gender. We argue that a core ethical debate surrounding the use of regression in risk assessments is not simply one of bias or accuracy. Rather, it's one of purpose. If machine learning is operationalized merely in the service of predicting individual future crime, then it becomes difficult to break cycles of criminalization that are driven by the iatrogenic effects of the criminal justice system itself. We posit that machine learning should not be used for prediction, but rather to surface covariates that are fed into a causal model for understanding the social, structural and psychological drivers of crime. We propose an alternative application of machine learning and causal inference away from predicting risk scores to risk mitigation.
Translating Basic Research Into Clinical Practice Mucins , Mucus , and Sputum *

Normal airway mucus lines the epithelial surface and provides an important innate immune function by detoxifying noxious molecules and by trapping and removing pathogens and particulates from the airway via mucociliary clearance. The major macromolecular constituents of normal mucus, the mucin g1ycoproteins, are large, heavily g1ycosylated proteins with a defining feature of tandemly repeating sequences of amino acids rich in serine and threonine, the linkage sites for large carbohydrate structures. The mucins are composed of two major families: secreted mucins and membrane-associated mucins. Membrane-associated mucins have been reported to function as cell surface receptors for pathogens and to activate intracellular signaling pathways. The biochemical and cellular functions for secreted mucin glycoproteins have not been definitively assigned. In contrast to normal mucus, sputum production is the hallmark of chronic inflammatory airway diseases such as asthma, chronic bronchitis, and cystic fibrosis (CF). Sputum has altered macromolecular composition and biophysical properties which vary with disease, but unifying features are failure of mucociliary clearance, resulting in airway obstruction, and failure of innate inunune properties. Mucin glycoprotein overproduction and hypersecretion are common features of chronic inflammatory airway disease, and this has been the underlying rationale to investigate the mechanisms of mucin gene regulation and mucin secretion. However, in some pathologic conditions such as CF, airway sputum contains little intact mucin and has increased content of several macromolecules including DNA, filamentous actin, lipids, and proteoglycans. This review will highlight the most recent insights on mucus biology in health and disease. (CHEST 2009; 135:505-512)
Proteome Scale Characterization of Human S-Acylated Proteins in Lipid Raft-enriched and Non-raft Membranes*

Protein S-acylation (palmitoylation), a reversible post-translational modification, is critically involved in regulating protein subcellular localization, activity, stability, and multimeric complex assembly. However, proteome scale characterization of S-acylation has lagged far behind that of phosphorylation, and global analysis of the localization of S-acylated proteins within different membrane domains has not been reported. Here we describe a novel proteomics approach, designated palmitoyl protein identification and site characterization (PalmPISC), for proteome scale enrichment and characterization of S-acylated proteins extracted from lipid raft-enriched and non-raft membranes. In combination with label-free spectral counting quantitation, PalmPISC led to the identification of 67 known and 331 novel candidate S-acylated proteins as well as the localization of 25 known and 143 novel candidate S-acylation sites. Palmitoyl acyltransferases DHHC5, DHHC6, and DHHC8 appear to be S-acylated on three cysteine residues within a novel CCX7–13C(S/T) motif downstream of a conserved Asp-His-His-Cys cysteine-rich domain, which may be a potential mechanism for regulating acyltransferase specificity and/or activity. S-Acylation may tether cytoplasmic acyl-protein thioesterase-1 to membranes, thus facilitating its interaction with and deacylation of membrane-associated S-acylated proteins. Our findings also suggest that certain ribosomal proteins may be targeted to lipid rafts via S-acylation, possibly to facilitate regulation of ribosomal protein activity and/or dynamic synthesis of lipid raft proteins in situ. In addition, bioinformatics analysis suggested that S-acylated proteins are highly enriched within core complexes of caveolae and tetraspanin-enriched microdomains, both cholesterol-rich membrane structures. The PalmPISC approach and the large scale human S-acylated protein data set are expected to provide powerful tools to facilitate our understanding of the functions and mechanisms of protein S-acylation.
Science Educational Outreach Programs That Benefit Students and Scientists

Both scientists and the public would benefit from improved communication of basic scientific research and from integrating scientists into education outreach, but opportunities to support these efforts are limited. We have developed two low-cost programs—"Present Your PhD Thesis to a 12-Year-Old" and "Shadow a Scientist”—that combine training in science communication with outreach to area middle schools. We assessed the outcomes of these programs and found a 2-fold benefit: scientists improve their communication skills by explaining basic science research to a general audience, and students' enthusiasm for science and their scientific knowledge are increased. Here we present details about both programs, along with our assessment of them, and discuss the feasibility of exporting these programs to other universities.
Dependence of adhesion properties of SMR L based adhesive on molecular weight of rubber

The viscosity, loop tack, peel and shear strength of five different molecular weights of standard Malaysian rubber based pressure sensitive adhesive were studied. Coumarone–indene resin and toluene were used as the tackifier and solvent respectively throughout the experiment. The adhesive was coated on polyethylene terephthalate substrate at a coating thickness of 30, 60, 90 and 120 μm using a Sheen hand coater. Viscosity of the adhesive was determined by a Haake rotary viscometer whereas loop tack, shear and peel strength was measured by a Llyod adhesion tester. Results show that viscosity of adhesive increases with increasing molecular weight of rubber. However, loop tack, shear and peel strength exhibit maximum value at a molecular weight of 8·5 × 104 where maximum wettability of adhesive on the substrate occurs. The adhesion property increases with coating thickness at this optimum molecular weight of rubber.
THE CONTRIBUTION OF AN HOURGLASS TIMER TO THE EVOLUTION OF PHOTOPERIODIC RESPONSE IN THE PITCHER‐PLANT MOSQUITO, WYEOMYIA SMITHII

Abstract Photoperiodism, the ability to assess the length of day or night, enables a diverse array of plants, birds, mammals, and arthropods to organize their development and reproduction in concert with the changing seasons in temperate climatic zones. For more than 60 years, the mechanism controlling photoperiodic response has been debated. Photoperiodism may be a simple interval timer, that is, an hourglasslike mechanism that literally measures the length of day or night or, alternatively, may be an overt expression of an underlying circadian oscillator. Herein, we test experimentally whether the rhythmic response in Wyeomyia smithii indicates a causal, necessary relationship between circadian rhythmicity and the evolutionary modification of photoperiodic response over the climatic gradient of North America, or may be explained by a simple interval timer. We show that a day‐interval timer is sufficient to predict the photoperiodic response of W. smithii over this broad geographic range and conclude that rhythmic responses observed in classical circadian‐based experiments alone cannot be used to infer a causal role for circadian rhythmicity in the evolution of photoperiodic time measurement. More importantly, we argue that the pursuit of circadian rhyth‐micity as the central mechanism that measures the duration of night or day has distracted researchers from consideration of the interval‐timing processes that may actually be the target of natural selection linking internal photoperiodic time measurement to the external seasonal environment.
A Sequential Monte Carlo/Time-Dependent Density Functional Theory

A transição eletrônica n→* do formaldeído em água é analisada usando-se um procedimento combinado e seqüencial de Monte Carlo (MC) clássico e mecânica quântica (MQ). MC é usado para gerar configurações do líquido para uso posterior em cálculos de MQ. Usando-se a representação espectral da teoria do funcional da densidade com uma base de funções gaussianas localizadas (TD-DFT/6-311++G(d,p)) cálculos são realizados em configurações estatisticamente descorrelacionadas para se obter o deslocamento solvatocrômico. Todos os resultados são obtidos usando-se uma representação onde o solvente é tratado como um campo eletrostático. O resultado médio obtido de 2300 cm é comparado com resultados teóricos anteriores. Análise é feita do valor do momento de dipolo efetivo da camada associada com as ligações de hidrogênio e como ela pode influenciar as camadas de solvatação mais externas.
Long-term prognosis of schizophrenia.

The question of determining prognostically relevant features for schizophrenia was approached with multivariate statistical methods applied to the data from the Bonn longitudinal study of 502 schizophrenic patients. In this study, personal interviews according to a clinical classification scheme allowed every patient to be ranked within each of three different outcome classes: psychopathological remission, occupational remission, and course type. Our multivariate analysis encompassed a total of 50 items pertinent to the time up to and including the first 6 months after the first psychotic manifestation. Despite the introduction of mathematical methods considerably more sophisticated than those employed in earlier studies, no satisfactory solution could be found to the problem of predicting end states of schizophrenia. Reliable predictions could be made only for 'extreme' end states (i.e. full remission versus (1) characteristic residues in the narrower sense; (2) total unemployment, or (3) surging or simple courses to mixed residues or to typical schizophrenic defect psychoses). Accordingly, sufficiently reliable assertions applied only to a minority of about 1/3 of patients, whereas for the majority of 2/3, no generalizable prognostication was possible (67-71% true-positive predictions on 36-63% of total population in extreme states). By contrast, our analyses have clearly uncovered a fundamental problem of investigations into the long-term prognosis of schizophrenia: the extreme dependence of results on the clinical definition of end states. The further the phenomenon 'end state' is qualitatively subdivided, the poorer and less reproducible is the mutual discrimination between intermediate states and the less reliable are allocations of patients to these intermediate states by means of multivariate classifiers. Furthermore, our analyses have also demonstrated the usefulness of multivariate, adaptive procedures for investigations into the structural properties of long-term courses, so that predictions might be considerably improved if more reliable definitions of schizophrenic end states are available.