Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeting a novel bone degradation pathway in primary bone cancer by inactivation of the collagen receptor uPARAP/Endo180

In osteosarcoma, a primary mesenchymal bone cancer occurring predominantly in younger patients, invasive tumour growth leads to extensive bone destruction. This process is insufficiently understood, cannot be efficiently counteracted and calls for novel means of treatment. The endocytic collagen receptor, uPARAP/Endo180, is expressed on various mesenchymal cell types and is involved in bone matrix turnover during normal bone growth. Human osteosarcoma specimens showed strong expression of this receptor on tumour cells, along with the collagenolytic metalloprotease, MT1–MMP. In advanced tumours with ongoing bone degeneration, sarcoma cells positive for these proteins formed a contiguous layer aligned with the degradation zones. Remarkably, osteoclasts were scarce or absent from these regions and quantitative analysis revealed that this scarcity marked a strong contrast between osteosarcoma and bone metastases of carcinoma origin. This opened the possibility that sarcoma cells might directly mediate bone degeneration. To examine this question, we utilized a syngeneic, osteolytic bone tumour model with transplanted NCTC‐2472 sarcoma cells in mice. When analysed in vitro, these cells were capable of degrading the protein component of surface‐labelled bone slices in a process dependent on MMP activity and uPARAP/Endo180. Systemic treatment of the sarcoma‐inoculated mice with a mouse monoclonal antibody that blocks murine uPARAP/Endo180 led to a strong reduction of bone destruction. Our findings identify sarcoma cell‐resident uPARAP/Endo180 as a central player in the bone degeneration of advanced tumours, possibly following an osteoclast‐mediated attack on bone in the early tumour stage. This points to uPARAP/Endo180 as a promising therapeutic target in osteosarcoma, with particular prospects for improved neoadjuvant therapy. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Determining Optimal Fluorescent Agent Concentrations in Dental Adhesive Resins for Imaging the Tooth/Restoration Interface

Abstract Fluorescent dyes like Rhodamine B (RB) have been used to identify the spatial distribution of adhesive restorative materials in the tooth/restoration interface. Potential effects of the addition of RB to dental adhesives were addressed in the past, but no further information is available on how to determine suitable concentrations of RB in these bonding agents for imaging in the confocal laser scanning microscope. This study provides systematical strategies for adding RB to viscous dental adhesive resins, focusing on the determination of the lowest range of dye concentrations necessary to achieve an acceptable image of the dentin/adhesive interface. It was demonstrated that optimized images of the resin distribution in dentin can be produced with 0.1–0.02 mg/mL of RB in the (tested) adhesives. Our approaches took into account aspects related to the dye concentration, photophysical parameters in different host media, specimen composition and morphology to develop a rational use of the fluorescent agent with the resin-based materials. Information gained from this work can help optimize labeling methods using dispersions of low-molecular-weight dyes in different monomer blend systems.
Colossal magnetoresistance is a Griffiths singularity.

It is now widely accepted that the magnetic transition in doped manganites that show large magnetoresistance is a type of percolation effect. This paper demonstrates that the transition should be viewed in the context of the Griffiths phase that arises when disorder suppresses a magnetic transition. This approach explains unusual aspects of susceptibility and heat capacity data from a single crystal of La0.7Ca0. 3MnO3.
Fine Needle Aspiration Cytology in the Management of Male Breast Masses

OBJECTIVE: To determine the utility and accuracy of fine needle aspiration cytology (FNAC) as well as its sensitivity, specificity and predictive value in the diagnosis of male breast masses. STUDY DESIGN: Data on male breast FNAC done between 1978 and 1997 were retrieved from the records of the cytopathology laboratory. FNAC diagnoses were categorized as positive, negative, inconclusive or unsatisfactory. Cytohistologic correlation was done with data front histopathology records. Sensitivity, specificity, diagnostic accuracy and predictive values of FNAC were calculated using standard statistical methods. RESULTS: Five hundred seven of 13,175 patients undergoing breast FNAC were males. Of them, 393/507 had satisfactory aspirates. Of these, 70 were positive (13.8%), 295 were negative (58%), and 29 were inconclusive (5.7%). A total of 114 FNACs (22.5%) were unsatisfactory. Histopathology was available in 97/507 cases. There were no false positive or false negative diagnoses. FNAC had a sensitivity, specificity and diagnostic accuracy of 100% for male breast lesions. CONCLUSION: This large study shows that FNAC is a very accurate tool for diagnosis of male breast lesions. It is highly sensitive and specific, with good cytohistologic correlation. FNAC should therefore be an integral part of the primary assessment of breast lumps in males.
Quantification of Olivine Using Fe Lα in Electron Probe Microanalysis (EPMA)

Abstract Quantification of first series transition metal Lα X-rays is hampered by absorption and in some cases transition probabilities (fluorescence yields) varying with chemical bonding. Compound mass absorption coefficients for Fe Lα were measured in the olivine solid solution series [Forsterite (Mg2SiO4) to Fayalite (Fe2SiO4)] and the mass absorption coefficients for Fe Lα absorbed by Fe were calculated. The mass absorption coefficients vary systematically between Fo83 and Fo0. Using the measured mass absorption coefficients for both standard and unknown and by correcting for a systematic discrepancy, consistent with varying partial fluorescence yields, a good agreement between calculated k-ratios and measured k-ratios is achieved. The systematic variations allow quantification of unknown k-ratios. The described method of quantification requires modification of matrix correction routines to allow standards and unknowns to have different mass absorption coefficients, and to incorporate solid solution mass absorption coefficients and partial fluorescence yield corrections derived from regression of experimental data.
Mitochondrial genome architecture in non‐alcoholic fatty liver disease

Non‐alcoholic fatty liver disease (NAFLD) is associated with mitochondrial dysfunction, a decreased liver mitochondrial DNA (mtDNA) content, and impaired energy metabolism. To understand the clinical implications of mtDNA diversity in the biology of NAFLD, we applied deep‐coverage whole sequencing of the liver mitochondrial genomes. We used a multistage study design, including a discovery phase, a phenotype‐oriented study to assess the mutational burden in patients with steatohepatitis at different stages of liver fibrosis, and a replication study to validate findings in loci of interest. We also assessed the potential protein‐level impact of the observed mutations. To determine whether the observed changes are tissue‐specific, we compared the liver and the corresponding peripheral blood entire mitochondrial genomes. The nuclear genes POLG and POLG2 (mitochondrial DNA polymerase‐γ) were also sequenced. We observed that the liver mtDNA of patients with NAFLD harbours complex genomes with a significantly higher mutational (1.28‐fold) rate and degree of heteroplasmy than in controls. The analysis of liver mitochondrial genomes of patients with different degrees of fibrosis revealed that the disease severity is associated with an overall 1.4‐fold increase in mutation rate, including mutations in genes of the oxidative phosphorylation (OXPHOS) chain. Significant differences in gene and protein expression patterns were observed in association with the cumulative number of OXPHOS polymorphic sites. We observed a high degree of homology (∼98%) between the blood and liver mitochondrial genomes. A missense POLG p.Gln1236His variant was associated with liver mtDNA copy number. In conclusion, we have demonstrated that OXPHOS genes contain the highest number of hotspot positions associated with a more severe phenotype. The variability of the mitochondrial genomes probably originates from a common germline source; hence, it may explain a fraction of the ‘missing heritability’ of NAFLD. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
ALK oncoproteins in atypical inflammatory myofibroblastic tumours: novel RRBP1‐ALK fusions in epithelioid inflammatory myofibroblastic sarcoma

ALK oncogenic activation mechanisms were characterized in four conventional spindle‐cell inflammatory myofibroblastic tumours (IMT) and five atypical IMT, each of which had ALK genomic perturbations. Constitutively activated ALK oncoproteins were purified by ALK immunoprecipitation and electrophoresis, and were characterized by mass spectrometry. The four conventional IMT had TPM3/4‐ALK fusions (two cases) or DCTN1‐ALK fusions (two cases), whereas two atypical spindle‐cell IMT had TFG‐ALK and TPM3‐ALK fusion in one case each, and three epithelioid inflammatory myofibroblastic sarcomas had RANBP2‐ALK fusions in two cases, and a novel RRBP1‐ALK fusion in one case. The epithelioid inflammatory myofibroblastic sarcoma with RRBP1‐ALK fusion had cytoplasmic ALK expression with perinuclear accentuation, different from the nuclear membranous ALK localization in epithelioid inflammatory myofibroblastic sarcomas with RANBP2‐ALK fusions. Evaluation of three additional uncharacterized epithelioid inflammatory myofibroblastic sarcomas with ALK cytoplasmic/perinuclear‐ accentuation expression demonstrated RRBP1‐ALK fusion in two cases. These studies show that atypical spindle‐cell IMT can utilize the same ALK fusion mechanisms described previously in conventional IMT, whereas in clinically aggressive epithelioid inflammatory myofibroblastic sarcoma we identify a novel recurrent ALK oncogenic mechanism, resulting from fusion with the RRBP1 gene. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Transforming growth factor-β1 antisense oligodeoxynucleotides block interstitial fibrosis in unilateral ureteral obstruction

Transforming growth factor-β1 antisense oligodeoxynucleotides block interstitial fibrosis in unilateral ureteral obstruction. Background Interstitial expression of transforming growth factor-β1 (TGF-β1) is important in tubulointerstitial fibrosis, a common process in most progressive renal diseases. However, no effective therapy for progressive interstitial fibrosis is known. Recently, we developed an artificial viral envelope (AVE)-type hemagglutinating virus of Japan (HVJ) liposome-mediated retrograde ureteral gene transfer method, which allowed us to introduce the genetic material selectively into renal interstitial fibroblasts. Method We introduced antisense or scrambled oligodeoxynucleotides (ODNs) for TGF-β1 into interstitial fibroblasts in rats with unilateral ureteral obstruction, a model of interstitial fibrosis, to block interstitial fibrosis by retrograde ureteral injection of AVE-type HVJ liposomes. Results TGF-β1 and type I collagen mRNA increased markedly in the interstitium of untreated obstructed kidneys, and those were not affected by scrambled ODN transfection. Northern analysis and in situ hybridization revealed that the levels of TGF-β1 and type I collagen mRNA were dramatically decreased in antisense ODN-transfected obstructed kidneys. Consequently, the interstitial fibrotic area of the obstructed kidneys treated with antisense ODN was significantly less than that of the obstructed kidneys untreated or treated with scrambled ODN. Conclusion The introduction of TGF-β1 antisense ODN into interstitial fibroblasts may be a potential therapeutic maneuver for interstitial fibrosis.
Incidental findings on magnetic resonance imaging in patients with tinnitus

Introduction: Tinnitus is "a sound in one ear or both ears, such as buzzing, ringing, or whistling, occurring without an external stimulus. " Magnetic resonance imaging (MRI) is a well-established, cost-effective investigation for the patients with tinnitus. Aim: The purpose of the study was to define the frequency of incidental findings on MRI scans, of patients with a history of tinnitus but with normal clinical examination, audiometry and otoacoustic emissions. Materials and Methods: A total of 62 patients were enrolled for the present study with a history of gradually increasing tinnitus and normal clinical ENT examination. All these patients underwent MRI scan to find out any lesion that would cause tinnitus. Results and Conclusion: In the present study, evaluation of MRI scans of 62 patients with gradually increasing tinnitus was done, with ipsilateral vestibular schwannoma and neurofibromatosis II being diagnosed in 1 patient (1.61%) each. Incidental findings were demonstrated in 26 cases (41.93%); with 8 cases (12.90%) of white matter lesions, 5 cases (8.66%) of vascular anomalies, 3 cases (4.83%) of arachnoid cyst, 2 cases (3.22%) of empty sella, 4 cases (6.45%) of sinus involvement, 2 cases (3.22%) of cerebral atrophy and 2 cases (3.22%) of vascular infarcts, though none of these findings were serious and neither warranted an urgent surgical intervention but a few cases required assessment by other specialties and were referred accordingly.
Auxin promotes susceptibility to Pseudomonas syringae via a mechanism independent of suppression of salicylic acid-mediated defenses.

Auxin is a key plant growth regulator that also impacts plant-pathogen interactions. Several lines of evidence suggest that the bacterial plant pathogen Pseudomonas syringae manipulates auxin physiology in Arabidopsis thaliana to promote pathogenesis. Pseudomonas syringae strategies to alter host auxin biology include synthesis of the auxin indole-3-acetic acid (IAA) and production of virulence factors that alter auxin responses in host cells. The application of exogenous auxin enhances disease caused by P. syringae strain DC3000. This is hypothesized to result from antagonism between auxin and salicylic acid (SA), a major regulator of plant defenses, but this hypothesis has not been tested in the context of infected plants. We further investigated the role of auxin during pathogenesis by examining the interaction of auxin and SA in the context of infection in plants with elevated endogenous levels of auxin. We demonstrated that elevated IAA biosynthesis in transgenic plants overexpressing the YUCCA 1 (YUC1) auxin biosynthesis gene led to enhanced susceptibility to DC3000. Elevated IAA levels did not interfere significantly with host defenses, as effector-triggered immunity was active in YUC1-overexpressing plants, and we observed only minor effects on SA levels and SA-mediated responses. Furthermore, a plant line carrying both the YUC1-overexpression transgene and the salicylic acid induction deficient 2 (sid2) mutation, which impairs SA synthesis, exhibited additive effects of enhanced susceptibility from both elevated auxin levels and impaired SA-mediated defenses. Thus, in IAA overproducing plants, the promotion of pathogen growth occurs independently of suppression of SA-mediated defenses.
High cytokinin levels induce a hypersensitive-like response in tobacco.

BACKGROUND AND AIMS Cytokinins are positive regulators of shoot development. However, it has previously been demonstrated that efficient activation of the cytokinin biosynthesis gene ipt can cause necrotic lesions and wilting in tobacco leaves. Some plant pathogens reportedly use their ability to produce cytokinins in disease development. In response to pathogen attacks, plants can trigger a hypersensitive response that rapidly kills cells near the infection site, depriving the pathogen of nutrients and preventing its spread. In this study, a diverse set of processes that link ipt activation to necrotic lesion formation were investigated in order to evaluate the potential of cytokinins as signals and/or mediators in plant defence against pathogens. METHODS The binary pOp-ipt/LhGR system for dexamethasone-inducible ipt expression was used to increase endogenous cytokinin levels in transgenic tobacco. Changes in the levels of cytokinins and the stress hormones salicylic, jasmonic and abscisic acid following ipt activation were determined by ultra-performance liquid chromatography-electrospray tandem mass spectrometry (UPLC-MS/MS). Trends in hydrogen peroxide content and lipid peroxidation were monitored using the potassium iodide and malondialdehyde assays. The subcellular distribution of hydrogen peroxide was investigated using 3,3'-diaminobenzidine staining. The dynamics of transcripts related to photosynthesis and pathogen response were analysed by reverse transcription followed by quantitative PCR. The effects of cytokinins on photosynthesis were deciphered by analysing changes in chlorophyll fluorescence and leaf gas exchange. KEY RESULTS Plants can produce sufficiently high levels of cytokinins to trigger fast cell death without any intervening chlorosis - a hallmark of the hypersensitive response. The results suggest that chloroplastic hydrogen peroxide orchestrates the molecular responses underpinning the hypersensitive-like response, including the inhibition of photosynthesis, elevated levels of stress hormones, oxidative membrane damage and stomatal closure. CONCLUSIONS Necrotic lesion formation triggered by ipt activation closely resembles the hypersensitive response. Cytokinins may thus act as signals and/or mediators in plant defence against pathogen attack.
Combined small RNA and degradome sequencing reveals novel miRNAs and their targets in response to low nitrate availability in maize.

BACKGROUND AND AIMS MicroRNAs (miRNAs) play an important role in the responses and adaptation of plants to many stresses including low nitrogen (LN). Characterizing relevant miRNAs will improve our understanding of nitrogen (N) use efficiency and LN tolerance and thus contribute to sustainable maize production. The objective of this study was to identify novel and known miRNAs and their targets involved in the response and adaptation of maize (Zea mays) to LN stress. METHODS MiRNAs and their targets were identified by combined analysis of deep sequencing of small RNA and degradome libraries. The identity of target genes was confirmed by gene-specific RNA ligase-mediated rapid amplification of 5' cDNA ends (RLM-RACE) and by quantitative expression analysis. KEY RESULTS Over 150 million raw reads of small RNA and degradome sequence data were generated. A total of 46 unique mature miRNA sequences belonging to 23 maize miRNA families were sequenced. Eighty-five potentially new miRNAs were identified, with corresponding miRNA* also identified for 65 of them. Twenty-five new miRNAs showed >2-fold relative change in response to LN. In addition to known miR169 species, two novel putative miR169 species were identified. Deep sequencing of miRNAs and the degradome, and RLM-RACE and quantitative polymerase chain reaction (PCR) analyses of their targets showed that miRC10- and miRC68-mediated target cleavage may play a major role among miR169 families in the adaptation to LN by maize seedlings. CONCLUSIONS Small RNA and degradome sequencing combined with quantitative reverse transcription-PCR and RLM-RACE verification enabled the efficient identification of miRNAs and their target genes. The generated data sets and the two novel miR169 species that were identified will contribute to our understanding of the physiological basis of adaptation to LN stress in maize plants.
Adverse Cerebral Outcomes after Coronary Bypass Surgery

Background Acute changes in cerebral function after elective coronary bypass surgery are a difficult clinical problem. We carried out a multicenter study to determine the incidence and predictors of — and the use of resources associated with — perioperative adverse neurologic events, including cerebral injury. Methods In a prospective study, we evaluated 2108 patients from 24 U.S. institutions for two general categories of neurologic outcome: type I (focal injury, or stupor or coma at discharge) and type II (deterioration in intellectual function, memory deficit, or seizures). Results Adverse cerebral outcomes occurred in 129 patients (6.1 percent). A total of 3.1 percent had type I neurologic outcomes (8 died of cerebral injury, 55 had nonfatal strokes, 2 had transient ischemic attacks, and 1 had stupor), and 3.0 percent had type II outcomes (55 had deterioration of intellectual function and 8 had seizures). Patients with adverse cerebral outcomes had higher in-hospital mortality (21 percent of patients .
Evaluation of Parotid Gland Lesions with Standard Ultrasound, Color Duplex Sonography, Sonoelastography, and Acoustic Radiation Force Impulse Imaging – a Pilot Study

Abstract Purpose: To evaluate the impact of standard ultrasound (US), color duplex sonography (CDS), sonoelastography (SE), and acoustic radiation force impulse (ARFI) imaging in the differentiation of parotid gland lesions. Materials and Methods: From September 2010 to February 2011, 33 parotid gland lesions of 32 patients were included in this study. Patients underwent high-resolution B-mode US (THI, 9 – 14 MHz), CDS, SE, and ARFI quantification. Then parotidectomy was performed and samples were analyzed by (immuno-) histology. Data was extracted via unpaired t-test and expressed in p-values. Results: There were 12 Wathin‘s tumors (WT), 11 pleomorphic adenomas (PA), 3 other benign tumors, 3 ductal dilatations, 2 neuroendocrine carcinomas, 1 non-Hodgkin lymphoma, and 1 malignant melanoma metastasis. In B-mode US, acoustic enhancement showed statistical significance between PA and WT (p < 0.005), and CDS determined different vascularization patterns (p < 0.0005). While SE did not visualize any significant difference between PA and WT, ARFI quantification determined different mean values for both entities (p < 0.003). Conclusion: B-mode US, CDS, and ARFI quantification distinguish PA from WT. The predictive value of the modern techniques for the differentiation of benign and malignant parotid lesions has to be assessed in a larger series.
From bad to worse: when lung cancer complicates idiopathic pulmonary fibrosis

Patients with idiopathic pulmonary fibrosis have a significantly increased risk for the development of lung cancer. The morbidity and mortality of this disease combination are substantial, and, unfortunately, there are currently few data to help guide clinicians in its diagnosis and treatment. In a recent issue of this journal, Hwang et al presented one of the first studies to evaluate lung cancer in patients with idiopathic pulmonary fibrosis at the molecular level. They demonstrate variants in regulators of the cell cycle, which are known to be important in malignant transformation and may also be important in the pathogenesis of idiopathic pulmonary fibrosis. Further understanding of the pathogenic overlap between lung cancer and idiopathic pulmonary fibrosis could help point the direction to specific diagnostic modalities and targeted treatment of both conditions in the future. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.