Miracle-dz/UniFAR-FTUs huggingface dataset:
Mammographic density: a hormonally responsive risk factor for breast cancer

Mammographic density refers to radiologically dense breast tissue, and reflects variations in the tissue composition of the breast. It is positively associated with collagen and epithelial and non-epithelial cells, and negatively associated with fat. There is extensive evidence that mammographic density is a risk factor for breast cancer, independent of other risk factors, and is associated with large relative and attributable risks for the disease. The epidemiology of mammographic density, notably the inverse association with age, is consistent with it being a marker of susceptibility to breast cancer. Cumulative exposure to mammographic density may be an important determinant of the age-specific incidence of breast cancer in the population. All risk factors for breast cancer must ultimately exert their influence by an effect on the breast, and these findings suggest that, for at least some risk factors, this influence includes an effect on the number of cells and the quantity of collagen in the breast, which is reflected in differences in mammographic density. Many of the genetic and environmental factors that influence the risk of breast cancer affect the proliferative activity and quantity of stromal and epithelial tissue in the breast, and these effects are reflected in differences in mammographic density among women of the same age. Some of these influences include endogenous and exogenous hormones, and the menopause. A better understanding of the factors that influence the response of breast tissue to these hormonal exposures may lead to an improved understanding of the aetiology of mammographic density and of breast cancer.
Exogenous Glutathione Completes the Defense against Oxidative Stress in Haemophilus influenzae

ABSTRACT Since they are equipped with several strategies by which they evade the antimicrobial defense of host macrophages, it is surprising that members of the genus Haemophilus appear to be deficient in common antioxidant systems that are well established to protect prokaryotes against oxidative stress. Among others, no genetic evidence for glutathione (γ-Glu-Cys-Gly) (GSH) biosynthesis or for alkyl hydroperoxide reduction (e.g., the Ahp system characteristic or enteric bacteria) is apparent from the Haemophilus influenzae Rd genome sequence, suggesting that the organism relies on alternative systems to maintain redox homeostasis or to reduce small alkyl hydroperoxides. In this report we address this apparent paradox for the nontypeable H. influenzae type strain NCTC 8143. Instead of biosynthesis, we could show that this strain acquires GSH by importing the thiol tripeptide from the growth medium. Although such GSH accumulation had no effect on growth rates, the presence of cellular GSH protected against methylglyoxal, tert-butyl hydroperoxide (t-BuOOH), and S-nitrosoglutathione toxicity and regulated the activity of certain antioxidant enzymes. H. influenzae NCTC 8143 extracts were shown to contain GSH-dependent peroxidase activity with t-BuOOH as the peroxide substrate. The GSH-mediated protection against t-BuOOH stress is most probably catalyzed by the product of open reading frame HI0572 (Prx/Grx), which we isolated from a genomic DNA fragment that confers wild-type resistance to t-BuOOH toxicity in the Ahp-negative Escherichia coli strain TA4315 and that introduces GSH-dependent alkyl hydroperoxide reductase activity into naturally GSH peroxidase-negative E. coli. Finally, we demonstrated that cysteine is an essential amino acid for growth and that cystine, GSH, glutathione amide, and cysteinylglycine can be catabolized in order to complement cysteine deficiency.
Basis of Cellular Autonomy in the Subsceptibility to Carcinogenesis

This paper summarizes our contributions in the basic understanding of the different susceptibility of the mammary gland to carcinogenesis according to age and parity history. Mammary carcinomas induced by the administration of 7,12-dimethylbenz-(DMBA) to young virgin rats arise from undifferentiated terminal ductal structures called terminal end buds (TEBs). TEBs, that normally differentiate into alveolar buds (ABs) and lobules, under the influence of DMBA develop intraductal proliferations which progress to carcinoma. The high susceptibility of the young virgin rat TEBs to neoplastic transformation is due to its large proliferative compartment, with cells cycling every 10 hours, and to a higher 3H-DMBA uptake. Progressive differentiation of TEBs into ABs and lobules or their regression to terminal ducts (TDs) is seen with aging. Complete differentiation of the gland is attained through pregnancy and lactation or through exogenous administration of chorionic gonadotrophin. The greater differentiation of the gland is manifested as permanent structural changes, consisting in the disappearance of TEBs and in a diminution of the number of TDs due to their differentiation into ABs and lobules. This greater differentiation results in a diminished or total refractoriness of the gland to the carcinogen because ABs and lobules have a lower proliferative compartment, and a longer cell cycle than TEBs and TDs. Cells of parous rats have both in vivo and in vitro lower DMBA-DNA binding capacity, lower DNA synthesis and greater ability to repair DMBA-damaged DNA than cells of young virgin rats. The more efficient DNA repair capacity of the parous rat mammary gland is demonstrated by the induction of unscheduled DNA synthesis and a removal of DMBA-DNA adducts.
Phosphoproteomic identification of targets of the Arabidopsis sucrose nonfermenting-like kinase SnRK2.8 reveals a connection to metabolic processes

SnRK2.8 is a member of the sucrose nonfermenting-related kinase family that is down-regulated when plants are deprived of nutrients and growth is reduced. When this kinase is over expressed in Arabidopsis, the plants grow larger. To understand how this kinase modulates growth, we identified some of the proteins that are phosphorylated by this kinase. A new phosphoproteomic method was used in which total protein from plants overexpressing the kinase was compared with total protein from plants in which the kinase was inactivated. Protein profiles were compared on two-dimensional gels following staining by a dye that recognizes phosphorylated amino acids. Candidate target proteins were confirmed with in vitro phosphorylation assays, using the kinase and target proteins that were purified from Escherichia coli. Seven target proteins were confirmed as being phosphorylated by SnRK2.8. Certain targets, such as 14-3-3 proteins, regulate as yet unidentified proteins, whereas other targets, such as glyoxalase I and ribose 5-phosphate isomerase, detoxify byproducts from glycolysis and catalyze one of the final steps in carbon fixation, respectively. Also, adenosine kinase and 60S ribosomal protein were confirmed as targets of SnRK2.8. Using mass spectrometry, we identified phosphorylated residues in the SnRK2.8, the 14-3-3κ, and the 14-3-3χ. These data show that the expression of SnRK2.8 is correlated with plant growth, which may in part be due to the phosphorylation of enzymes involved in metabolic processes.
Ocular Immunology and Inflammation

Purpose: To show the current status of multimodal imaging and its role in supporting an early diagnosis of sympathetic ophthalmia. Methods: The diagnosis is mainly clinical supported with ancillary investigations; mainly fluorescein angiography and others, including indocyanine angiography optical coherence tomography (OCT), OCT enhanced depth imaging, autofluorescence imaging, and ultrasonography. Results: Various imaging modalities such as OCT, autofluorescence imaging and angiography are critical in the diagnosis and management of sympathetic ophthalmia. The clinician must make adequate use of such ancillary investigations in the management of the patients. Conclusions: Sympathetic ophthalmia is a rare, bilateral inflammation of the uveal tract following penetrating trauma or surgery in one eye. The intraocular inflammation requires a prompt diagnosis so that the treatment can be initiated as early as possible.
Saphenous vein patch versus polytetrafluoroethylene patch after carotid endarterectomy.

Although carotid patch angioplasty has been performed on a selective or routine basis in all large series of carotid endarterectomy, the choice of patch material still remains in question. The objective of this study has been a prospective randomized evaluation of the relative risks and benefits of saphenous vein patch versus PTFE patch material for carotid endarterectomy. During a 4-year period, 84 patients undergoing 95 carotid endarterectomies were randomized into two groups: 45 venous patch (n = 40) and 50 PTFE patch (n = 44). All operations were carried out under general anesthesia and systematic placement of a shunt. The patients were evaluated at 1, 3, 6 months and every year with doppler, periorbitary photoplethysmography, intravenous digital subtraction angiography, and neurologic assessment (mean follow-up 29 +/- 1 month). Operative time among patients having PTFE patch was significantly longer (p < 0.05) than among those having saphenous vein patch, due to bleeding from suture holes. Perioperatively, no neurologic complications or deaths were observed in venous patch patients, however there was a permanent stroke and one death from arterial wall disruption in the PTFE patch group. The incidence of aneurysmal dilatation in the saphenous vein patch group (15.5%) was higher than for the PTFE patch group (2%). On late follow-up, no deaths, carotid thrombosis or patch rupture were observed in either group. Recurrent stenosis occurred in 2 cases having PTFE patch. One reoperation for recurrence was required. In addition, one patient with PTFE patch angioplasty developed an infected false aneurysm at 7 months. (ABSTRACT TRUNCATED AT 250 WORDS)
Brief Report: The lincRNA Hotair Is Required for Epithelial‐to‐Mesenchymal Transition and Stemness Maintenance of Cancer Cell Lines

Hotair is a member of the recently described class of noncoding RNAs called lincRNA (large intergenic noncoding RNA). Various studies suggest that Hotair acts regulating epigenetic states by recruiting chromatin‐modifying complexes to specific target sequences that ultimately leads to suppression of several genes. Although Hotair has been associated with metastasis and poor prognosis in different tumor types, a deep characterization of its functions in cancer is still needed. Here, we investigated the role of Hotair in the scenario of epithelial‐to‐mesenchymal transition (EMT) and in the arising and maintenance of cancer stem cells (CSCs). We found that treatment with TGF‐β1 resulted in increased Hotair expression and triggered the EMT program. Interestingly, ablation of Hotair expression by siRNA prevented the EMT program stimulated by TGF‐β1, and also the colony‐forming capacity of colon and breast cancer cells. Furthermore, we observed that the colon CSC subpopulation (CD133+/CD44+) presents much higher levels of Hotair when compared with the non‐stem cell subpopulation. These results indicate that Hotair acts as a key regulator that controls the multiple signaling mechanisms involved in EMT. Altogether, our data suggest that the role of Hotair in tumorigenesis occurs through EMT triggering and stemness acquisition. Stem Cells 2013;31:2827–2832
Disease-Specific Trends of Comorbidity Coding and Implications for Risk Adjustment in Hospital Administrative Data.

OBJECTIVE To investigate changes in comorbidity coding after the introduction of diagnosis related groups (DRGs) based prospective payment and whether trends differ regarding specific comorbidities. DATA SOURCES Nationwide administrative data (DRG statistics) from German acute care hospitals from 2005 to 2012. STUDY DESIGN Observational study to analyze trends in comorbidity coding in patients hospitalized for common primary diseases and the effects on comorbidity-related risk of in-hospital death. EXTRACTION METHODS Comorbidity coding was operationalized by Elixhauser diagnosis groups. The analyses focused on adult patients hospitalized for the primary diseases of heart failure, stroke, and pneumonia, as well as hip fracture. PRINCIPAL FINDINGS When focusing the total frequency of diagnosis groups per record, an increase in depth of coding was observed. Between-hospital variations in depth of coding were present throughout the observation period. Specific comorbidity increases were observed in 15 of the 31 diagnosis groups, and decreases in comorbidity were observed for 11 groups. In patients hospitalized for heart failure, shifts of comorbidity-related risk of in-hospital death occurred in nine diagnosis groups, in which eight groups were directed toward the null. CONCLUSIONS Comorbidity-adjusted outcomes in longitudinal administrative data analyses may be biased by nonconstant risk over time, changes in completeness of coding, and between-hospital variations in coding. Accounting for such issues is important when the respective observation period coincides with changes in the reimbursement system or other conditions that are likely to alter clinical coding practice.
Genetic eye research in Tasmania: a historical overview

Although considerable recent work on hereditary eye diseases in Tasmanian families has been published, much of this depended on a century of meticulous pedigree collection by earlier clinical researchers. This article reviews some of the historical papers and the importance they have played in gene discovery and understanding of ophthalmic genetics. Tasmanian families have contributed to the identification of genes for X‐linked megalocornea, Leber's hereditary optic neuropathy, retinitis pigmentosa, congenital cataract, ptosis, keratoconus, glaucoma and myopia. The true value of the Tasmanian pedigrees will be realized with the translation of genetic discoveries into early diagnosis and treatment for these eye diseases.
Exacerbation of coagulopathy with concurrent bone marrow necrosis, hepatic and renal dysfunction secondary to all‐trans retinoic acid therapy for acute promyelocytic leukemia

A 22‐year‐old female presented with acute promyelocytic leukemia (APL). Treatment with all‐trans retinoic acid (ATRA) resulted in a severe exacerbation of the coagulopathy 5 days after its introduction. This was complicated by bone marrow necrosis, parenchymal liver damage and acute tubular necrosis. Temporary cessation of the drug and subsequent dose reduction was effective in controlling the coagulopathy. © 1997 John Wiley & Sons, Ltd.
On Combining a Semi-Calibrated Stereo Camera and Massive Parallelism for Fast Plane Extraction

We present a novel methodology that combines stereo vision and parallel processing, based on GPU and the use of binary descriptors, for fast plane extraction. Typical stereo algorithms require an image rectification stage that has to run in a frame-to-frame basis, increasing the computational burden and with the possibility of compromising high frame rate operation. Hence, we propose to use a semi-calibrated stereo approach, meaning that only calibration of extrinsic parameters of the stereo rig is carried out, thus avoiding a rectification process of the frames captured by the stereo camera. For the latter, we rely on feature matching of salient points detected on the stereo images, from which image correspondences are obtained. These correspondences are triangulated in order to generate a point cloud that is passed to a plane fitting module. As feature matching is a heavy task, we present a novel GPU architecture to accelerate such process, thus achieving real-time performance of up to 50 fps for the whole process. To demonstrate our approach, we also present an augmented reality application that exploits the planes extracted with our proposed methodology.
Auditory short-term memory persistence for tonal signals in a songbird.

This paper presents an animal model for studying the persistence of auditory memory for tonal signals. Five European starlings (Sturnus vulgaris) were trained in a Go/NoGo delayed nonmatching-to-sample task to discriminate between a series of identical "sample stimuli" and a single "test stimulus. " Frequencies of sample and test stimuli should be classified as being either the same or different. The performance of the birds is measured as the percentage of correct classifications. Three parameters were varied: The delay between sample and test stimuli, the number of sample stimuli presented before the test stimulus, and the salience of the difference between sample and test stimuli. Auditory memory persistence time was estimated as a function of the delay between the last sample stimulus and the test stimulus. The performance of the birds deteriorated with increasing delay before the test stimulus. Increasing the number of sample stimuli in the series of tones presented before the test stimulus improved performance. Performance was also better for more salient differences between sample and test stimuli. The individual auditory memory persistence time varied between 4 and 20 s.
Functional plasticity of paralogous diterpene synthases involved in conifer defense

The diversity of terpenoid compounds produced by plants plays an important role in mediating various plant–herbivore, plant–pollinator, and plant–pathogen interactions. This diversity has resulted from gene duplication and neofunctionalization of the enzymes that synthesize and subsequently modify terpenes. Two diterpene synthases in Norway spruce (Picea abies), isopimaradiene synthase and levopimaradiene/abietadiene synthase, provide the hydrocarbon precursors for most of the diterpene resin acids found in the defensive oleoresin of conifers. Although these paralogous enzymes are 91% identical at the amino acid level, one is a single-product enzyme, whereas the other is a multiproduct enzyme that forms completely different products. We used a rational approach of homology modeling, protein sequence comparison, domain swapping, and a series of reciprocal site-directed mutagenesis to identify the specific residues that direct the different product outcomes. A one-amino acid mutation switched the levopimaradiene/abietadiene synthase into producing isopimaradiene and sandaracopimaradiene and none of its normal products. Four mutations were sufficient to reciprocally reverse the product profiles for both of these paralogous enzymes while maintaining catalytic efficiencies similar to the wild-type enzymes. This study illustrates how neofunctionalization can result from relatively minor changes in protein sequence, increasing the diversity of secondary metabolites important for conifer defense.
The Interferon-induced Transmembrane Proteins, IFITM1, IFITM2, and IFITM3 Inhibit Hepatitis C Virus Entry*

Background: Interferon-induced transmembrane (IFITM) proteins limit a broad range of RNA viruses. Results: Tyrosine phosphorylation of IFITM2 and IFITM3, and S-palmitoylation of the IFITM proteins, are crucial for anti-hepatitis C virus (HCV) activity. Conclusion: IFITM2 and IFITM3 are able to limit HCV infection by targeting the late entry stages of the virus. Significance: IFITM proteins inhibit HCV at early and late stages of entry. The interferon-induced transmembrane (IFITM) family of proteins have recently been identified as important host effector molecules of the type I interferon response against viruses. IFITM1 has been identified as a potent antiviral effector against hepatitis C virus (HCV), whereas the related family members IFITM2 and IFITM3 have been described to have antiviral effects against a broad range of RNA viruses. Here, we demonstrate that IFITM2 and IFITM3 play an integral role in the interferon response against HCV and act at the level of late entry stages of HCV infection. We have established that in hepatocytes, IFITM2 and IFITM3 localize to the late and early endosomes, respectively, as well as the lysosome. Furthermore, we have demonstrated that S-palmitoylation of all three IFITM proteins is essential for anti-HCV activity, whereas the conserved tyrosine residue in the N-terminal domain of IFITM2 and IFITM3 plays a significant role in protein localization. However, this tyrosine was found to be dispensable for anti-HCV activity, with mutation of the tyrosine resulting in an IFITM1-like phenotype with the retention of anti-HCV activity and co-localization of IFITM2 and IFITM3 with CD81. In conclusion, we propose that the IFITM proteins act in a coordinated manner to restrict HCV infection by targeting the endocytosed HCV virion for lysosomal degradation and demonstrate that the actions of the IFITM proteins are indeed virus and cell-type specific.
Mutations, epimutations, and the developmental programming of the maize Suppressor‐mutator transposable element

Information about the structure, function and regulation of the maize Suppressormutator (Spm) transposable element has emerged from the genetic and molecular characterization of both deletion mutations and an unconventional type of reversible genetic change (epimutation). The element is subject to an epigenetic mechanism that can either stably inactivate it or specify one of a variety of heritable programs of differential element expression in development. The essay explores the relationship between the Spm element's epigenetic developmental programming mechanism and the determinative events central to plant development and differentiation.
Effect of restriction of placental growth on expression of IGFs in fetal sheep: relationship to fetal growth, circulating IGFs and binding proteins.

To determine whether tissue production of the IGFs is altered when fetal growth is retarded, IGF-I and -II mRNAs were measured in tissues of fetal sheep subjected to placental restriction and the relationships between IGF gene expression, circulating IGF protein and fetal growth were examined. The majority of potential placental attachment sites were surgically removed from the uterus of 12 non-pregnant ewes to restrict placental size in a subsequent pregnancy. Blood and tissues were collected at 121 days of gestation (term = 150) in 12 fetuses with restricted placental size and eight normal fetuses. IGF-I and IGF-II mRNA was detected by solution hybridization/ribonuclease protection assay in placenta and all fetal tissues studied. IGF-I mRNA was most abundant in skeletal muscle and liver and IGF-II mRNA was highest in kidney and lung. Restriction of placental size reduced fetal weight by 17% and reduced the pO2 (18%) and glucose concentration (23%) of fetal blood. Placental restriction also reduced IGF-I mRNA in fetal muscle (P < 0.002), lung (P < 0.05) and kidney (P < 0.01) but had no significant effect on IGF-II mRNA in any tissue. IGF-I mRNA in fetal liver, kidney and skeletal muscle correlated positively with the concentration of IGF-I protein in fetal blood (P < 0.01). There was no relationship between the concentration of IGF-II protein in fetal blood and IGF-II mRNA in any fetal tissue examined. The concentration of IGF-binding protein-3 (IGFBP-3) in fetal arterial blood plasma measured by RIA correlated positively with fetal weight and with plasma IGF-I. (ABSTRACT TRUNCATED AT 250 WORDS)