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  • 1
    Publication Date: 2014-06-20
    Description: Aim In case of mucinous adenocarcinoma (MA), cytologic atypia is usually mild to moderate, or may be absent in some cases, incurring a diagnostic pitfall in recognising MA in small tissue biopsy and cytology specimens. The purpose of this study was to evaluate the diagnostic accuracy of transthoracic fine needle aspiration (FNA) or core needle biopsy (CNB) for making a diagnosis of pulmonary MA. Methods We retrospectively reviewed a consecutive series of 185 patients who underwent curative operation for MA. Among those patients, 105 patients underwent preoperative percutaneous FNA (n=34) or CNB (n=79). Eight patients underwent FNA and CNB for the same tumour. Diagnostic accuracies of FNA and CNB for making a diagnosis of MA were evaluated, and the contribution of various clinicopathologic parameters to subtyping accuracy was analysed. Results Diagnostic accuracies of FNA and CNB in determining malignancy were 67.6% and 87.3%, respectively, and those for making a diagnosis of MA were 20.6% and 59.5%, respectively. Univariate analysis indicated that the type of biopsy procedure and prominent growth pattern of MA are significant factors for successful histologic diagnosis. Tumour nature on CT and the length of biopsy specimen were not related to successful diagnosis of histology subtyping of MA. Conclusions CNB appears to be feasible and accurate for diagnosing a MA. Prominent growth patterns of MA are significant factors for successful histologic diagnosis of MA.
    Keywords: Clinical diagnostic tests
    Print ISSN: 0021-9746
    Electronic ISSN: 1472-4146
    Topics: Medicine
    Published by BMJ Publishing Group
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  • 2
    Publication Date: 2021-07-21
    Description: The Tierra Blanca (TB) eruptive suite comprises the last four major eruptions of Ilopango caldera in El Salvador (≤45 ka), including the youngest Tierra Blanca Joven eruption (TBJ; ∼106 km3): the most voluminous event during the Holocene in Central America. Despite the protracted and productive history of explosive silicic eruptions at Ilopango caldera, many aspects regarding the longevity and the prevailing physicochemical conditions of the underlying magmatic system remain unknown. Zircon 238U‐230Th geochronology of the TB suite (TBJ, TB2, TB3, and TB4) reveals a continuous and overlapping crystallization history among individual eruptions, suggesting persistent melt presence in thermally and compositionally distinct magma reservoirs over the last ca. 80 kyr. The longevity of zircon is in contrast to previously determined crystallization timescales of 〈10 kyr for major mineral phases in TBJ. This dichotomy is explained by a process of rhyolitic melt segregation from a crystal‐rich refractory residue that incorporates zircon, whereas a new generation of major mineral phases crystallized shortly before eruption. Ti‐in‐zircon temperatures and amphibole geothermobarometry suggest that rhyolitic melt was extracted from different storage zones of the magma reservoir as indicated by distinct but synchronous thermochemical zircon histories among the TB suite eruptions. Zircon from TBJ and TB2 suggests magma differentiation within deeper and hotter parts of the reservoir, whereas zircon from TB3 and TB4 instead hints at crystallization in comparatively shallower and cooler domains. The assembly of the voluminous TBJ magma reservoir was also likely enhanced by cannibalization of hydrothermally altered components as suggested by low‐δ18O values in zircon (+4.5 ± 0.3‰).
    Description: Plain Language Summary: The collapse of a volcano edifice into its shallow magma chamber can produce one of the most dangerous single events in nature, known as a caldera‐forming eruption. The TBJ eruption in El Salvador is of this kind and occurred around 1,500 years ago, having a profound impact on Maya societies. Because of this, it is crucial to understand the inner workings of caldera‐forming eruptions to assess volcanic risks and their mitigation. Beneath Ilopango caldera, the micrometer‐sized radioisotopically datable mineral zircon grew within different storage levels of a silica‐rich magma reservoir suggesting continuous melt presence for up to ca. 80,000 years prior to eruption. The time information given by zircon contrasts with that extracted from other, more abundant minerals from the same rocks (〈10,000 years). We explain this time difference between coexisting minerals by the ability of melt to carry along small zircon crystals, whereas coeval, larger, and more abundant minerals are left behind in the partially solidified portion of the magma reservoir. Once the segregated melt coalesced in a shallower and dominantly liquid magma chamber, major minerals resumed crystallization shortly before eruption. In addition, this new magma incorporated parts of older magmatic rocks from preceding volcanic cycles, thus generating even larger magma volumes.
    Description: Key Points: U‐Th zircon ages for the last four explosive eruptions of Ilopango caldera reveal a long‐lived magma reservoir (〉80 kyr). Contrasting residence times for major minerals and zircon suggest extraction of zircon along with evolved melt from crystal residue. Melt extraction from vertically extensive, thermally zoned magma reservoir.
    Description: Deutsche Forschungsgemeinschaft (DFG) http://dx.doi.org/10.13039/501100001659
    Keywords: 549 ; 551.701 ; Central America ; Geochemistry ; Oxygen isotopes ; SIMS ; U‐series ; Zircon
    Type: article
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  • 3
    Publication Date: 2012-08-24
    Description: Purpose: To evaluate the usefulness of histopathologic scoring for survival prediction in patients with solitary pulmonary nodular (SPN) lung adenocarcinomas and to correlate the histopathologic scoring with the results of computed tomography (CT) and fluorine 18 fluorodeoxyglucose positron emission tomography (PET)/CT. Materials and Methods: This retrospective study was institutional review board approved and the requirement for informed consent was waived. A total of 148 patients with SPN lung adenocarcinoma underwent PET/CT and CT. Correlations between histopathologic scores estimated by using two predominant histologic subtypes from each surgically resected specimen and the mass of the nodule at CT or maximum standardized uptake value (SUV max ) at PET/CT were assessed. Disease-free survival (DFS) was estimated by using the Kaplan-Meier method, and the log-rank test was used to evaluate differences in each histopathologic subtype. Results: In 135 (91%) patients, tumors had a mixed subtype. The most frequently observed histologic subtypes, in decreasing order, were acinar (51%), lepidic (18%), solid (10%), and papillary (9%). DFS rates at 5 years were higher than 90% for the group of patients with nodules that showed the lepidic growth pattern, and 50% for patients with nodules that showed the micropapillary pattern. The pathologic score proved to be a significant predictor of DFS ( P 〈 .001). Both SUV max and the mass of the nodule were closely correlated with pathologic score. Conclusion: Pathologic scoring appears to help predict DFS in patients with SPN lung adenocarcinoma and shows close correlation with imaging biomarkers including the mass of the nodule at CT and SUV max at PET/CT. © RSNA, 2012
    Keywords: Chest Radiology, Biomarkers/Quantitative Imaging
    Print ISSN: 0033-8419
    Electronic ISSN: 1527-1315
    Topics: Medicine
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  • 4
    Publication Date: 2012-08-24
    Description: Purpose: To evaluate the safety and efficacy of pelvic arterial embolization (PAE) for the treatment of primary postpartum hemorrhage (PPH) and to determine the factors associated with clinical outcomes. Materials and Methods: This retrospective single-center study was institutional review board approved, and informed consent was waived. Outcomes were analyzed in 251 patients who underwent PAE for primary PPH between January 2000 and February 2011. Mode of delivery, causes of bleeding, detailed laboratory and treatment records, and clinical outcomes were recorded. Clinical success was defined as cessation of bleeding after initial session of PAE without the need for additional PAE or surgery. Univariate and multivariate analyses were performed to determine the factors related to clinical outcomes. Results: The clinical success rate was 86.5% (217 of 251). Among the 34 failed cases, 12 underwent repeat PAE, 16 underwent additional surgery, and three recovered with conservative management. Overall bleeding control was achieved in 98.0% (246 of 251) of the patients. Overall mortality was 2% (five of 251) after the first ( n = 3) or second ( n = 1) session of PAE or additional surgery ( n = 1). Among the 113 patients with long-term follow-up, 110 (97.3%) maintained a regular menstrual cycle and 11 had successful pregnancies. Univariate analysis showed that cesarean section delivery, disseminated intravascular coagulation (DIC), and massive transfusion of more than 10 red blood cell units were related to failed PAE. Multivariate analysis showed that DIC (odds ratio, 0.36; P = .04) and massive transfusion (odds ratio, 0.10; P 〈 .001) were significantly related to clinical failure. Conclusion: PAE is safe and effective for managing primary PPH. Patients with DIC and massive transfusion were likely to have poor results after PAE. © RSNA, 2012
    Keywords: Obstetric/Gynecologic Radiology, Interventional Radiology, Vascular Imaging
    Print ISSN: 0033-8419
    Electronic ISSN: 1527-1315
    Topics: Medicine
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  • 5
    Publication Date: 2013-04-17
    Description: Transmembrane proteins with unknown function 16 (TMEM16A) is a calcium-activated chloride channel (CaCC) important for neuronal, exocrine, and smooth muscle functions. TMEM16A belongs to a family of integral membrane proteins that includes another CaCC, TMEM16B, responsible for controlling action potential waveform and synaptic efficacy, and a small-conductance calcium-activated nonselective cation...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 6
    Publication Date: 2014-09-30
    Description: Insulin-like growth factor (IGF)-dependent and -independent antitumor activities of insulin-like growth factor binding protein-3 (IGFBP-3) have been proposed in human non-small cell lung cancer (NSCLC) cells. However, the mechanism underlying regulation of IGFBP-3 expression in NSCLC cells is not well understood. In this study, we show that activation of Akt, especially Akt3, plays a major role in the mRNA expression and protein stability of IGFBP-3 and thus antitumor activities of IGFBP-3 in NSCLC cells. When Akt was activated by genomic or pharmacologic approaches, IGFBP-3 transcription and protein stability were decreased. Conversely, suppression of Akt increased IGFBP-3 mRNA levels and protein stability in NSCLC cell lines. Characterization of the effects of constitutively active form of each Akt subtype (HA-Akt-DD) on IGFBP-3 expression in NSCLC cells and a xenograft model indicated that Akt3 plays a major role in the Akt-mediated regulation of IGFBP-3 expression and thus suppression of Akt effectively enhances the antitumor activities of IGFBP-3 in NSCLC cells with Akt3 overactivation. Collectively, these data suggest a novel function of Akt3 as a negative regulator of IGFBP-3, indicating the possible benefit of a combined inhibition of IGFBP-3 and Akt3 for the treatment of patients with NSCLC.
    Print ISSN: 0143-3334
    Electronic ISSN: 1460-2180
    Topics: Medicine
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  • 7
    Publication Date: 2013-07-16
    Description: During RNA interference and related gene regulatory pathways, the endonuclease Dicer cleaves precursor RNA molecules to produce microRNAs (miRNAs) and short interfering RNAs (siRNAs). Human cells encode a single Dicer enzyme that can associate with two different double-stranded RNA (dsRNA)-binding proteins, protein activator of PKR (PACT) and trans-activation response RNA-binding protein (TRBP). However, the functional redundancy or differentiation of PACT and TRBP in miRNA and siRNA biogenesis is not well understood. Using a reconstituted system, we show here that PACT and TRBP have distinct effects on Dicer-mediated dsRNA processing. In particular, we found that PACT in complex with Dicer inhibits the processing of pre-siRNA substrates when compared with Dicer and a Dicer–TRBP complex. In addition, PACT and TRBP show non-redundant effects on the production of different-sized miRNAs (isomiRs), which in turn alter target-binding specificities. Experiments using chimeric versions of PACT and TRBP suggest that the two N-terminal RNA-binding domains of each protein confer the observed differences in dsRNA substrate recognition and processing behavior of Dicer–dsRNA-binding protein complexes. These results support the conclusion that in humans, Dicer-associated dsRNA-binding proteins are important regulatory factors that contribute both substrate and cleavage specificity during miRNA and siRNA production.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 8
    Publication Date: 2013-10-16
    Description: Background Several phase II/III trials of anti–insulin-like growth factor 1 receptor (IGF-1R) monoclonal antibodies (mAbs) have shown limited efficacy. The mechanisms of resistance to IGF-1R mAb-based therapies and clinically applicable strategies for overcoming drug resistance are still undefined. Methods IGF-1R mAb cixutumumab efficacy, alone or in combination with Src inhibitors, was evaluated in 10 human head and neck squamous cell carcinoma (HNSCC) and six non–small cell lung cancer (NSCLC) cell lines in vitro in two- or three-dimensional culture systems and in vivo in cell line– or patient-derived xenograft tumors in athymic nude mice (n = 6–9 per group). Cixutumumab-induced changes in cell signaling and IGF-1 binding to integrin β3 were determined by Western or ligand blotting, immunoprecipitation, immunofluorescence, and cell adhesion analyses and enzyme-linked immunosorbent assay. Data were analyzed by the two-sided Student t test or one-way analysis of variance. Results Integrin β3–Src signaling cascade was activated by IGF-1 in HNSCC and NSCLC cells, when IGF-1 binding to IGF-1R was hampered by cixutumumab, resulting in Akt activation and cixutumumab resistance. Targeting integrin β3 or Src enhanced antitumor activity of cixutumumab in multiple cixutumumab-resistant cell lines and patient-derived tumors in vitro and in vivo. Mean tumor volume of mice cotreated with cixutumumab and integrin β3 siRNA was 133.7mm 3 (95% confidence interval [CI] = 57.6 to 209.8mm 3 ) compared with those treated with cixutumumab (1472.5mm 3 ; 95% CI = 1150.7 to 1794.3mm 3 ; P 〈 .001) or integrin β3 siRNA (903.2mm 3 ; 95% CI = 636.1 to 1170.3mm 3 ; P 〈 .001) alone. Conclusions Increased Src activation through integrin αβ3 confers considerable resistance against anti–IGF-1R mAb-based therapies in HNSCC and NSCLC cells. Dual targeting of the IGF-1R pathway and collateral integrin β3–Src signaling module may override this resistance.
    Electronic ISSN: 1460-2105
    Topics: Medicine
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  • 9
    Publication Date: 2013-03-22
    Description: Aims The association between alkaline phosphatase (ALP) and mortality was reported in several subgroups of patients. But, the role of ALP in overall coronary artery disease (CAD) patients after percutaneous coronary intervention (PCI) remains unknown. The aim of this study was to examine the prognostic value of the ALP level in patients with CAD who underwent PCI with drug-eluting stent (DES). Methods and results We prospectively included CAD patients who underwent PCI with DES. After exclusion of patients with liver disease and cancer, 1636 patients were selected for the analysis of clinical outcomes (median duration of follow-up; 762 days, inter-quartile range; 494–1068 days), and were classified into tertiles by baseline measurements of ALP (〈63, 63–78, and 〉78 IU/L). After adjustment of potential confounders including angiographic data, the independent and dose-dependent association was observed between tertile of ALP and the adjusted hazard ratio (HR) of all-cause mortality ( P for trend 〈 0.0001). Specifically, compared with the lowest ALP tertile, the adjusted HR of all-cause mortality in the highest tertile was 4.21 (95% confidence interval 2.03–8.71). In subgroup of patients with stable or unstable angina, a similar association was noted ( P for trend 〈 0.0001). In terms of cardiovascular mortality, myocardial infarction, and stent thrombosis, the adjusted HRs in the highest ALP tertile were 3.92 (1.37–11.20), 1.98 (0.91–4.29), and 2.73 (1.33–5.61), respectively, compared with the lowest tertile. Furthermore, evaluation of both ALP and C-reactive protein provided better predictive value than either alone. Interesting result suggesting the mechanism was that ALP was significantly associated with the presence of angiographic coronary calcification ( P for trend = 0.046). Conclusion Our study demonstrated that the higher serum ALP level is an independent predictor of mortality, myocardial infarction, and stent thrombosis in CAD patients after PCI with DES.
    Print ISSN: 0195-668X
    Electronic ISSN: 1522-9645
    Topics: Medicine
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  • 10
    Publication Date: 2014-02-07
    Description: Human immunodeficiency virus (HIV) incidence is an important measure for monitoring the epidemic and evaluating the efficacy of intervention and prevention trials. This study developed a high-throughput, single-measure incidence assay by implementing a pyrosequencing platform. We devised a signal-masking bioinformatics pipeline, which yielded a process error rate of 5.8 x 10 –4 per base. The pipeline was then applied to analyze 18,434 envelope gene segments (HXB2 7212 to 7601) obtained from 12 incident and 24 chronic patients who had documented HIV-negative and/or -positive tests. The pyrosequencing data were cross-checked by using the single-genome-amplification (SGA) method to independently obtain 302 sequences from 13 patients. Using two genomic biomarkers that probe for the presence of similar sequences, the pyrosequencing platform correctly classified all 12 incident subjects (100% sensitivity) and 23 of 24 chronic subjects (96% specificity). One misclassified subject's chronic infection was correctly classified by conducting the same analysis with SGA data. The biomarkers were statistically associated across the two platforms, suggesting the assay's reproducibility and robustness. Sampling simulations showed that the biomarkers were tolerant of sequencing errors and template resampling, two factors most likely to affect the accuracy of pyrosequencing results. We observed comparable biomarker scores between AIDS and non-AIDS chronic patients (multivariate analysis of variance [MANOVA], P = 0.12), indicating that the stage of HIV disease itself does not affect the classification scheme. The high-throughput genomic HIV incidence marks a significant step toward determining incidence from a single measure in cross-sectional surveys. IMPORTANCE Annual HIV incidence, the number of newly infected individuals within a year, is the key measure of monitoring the epidemic's rise and decline. Developing reliable assays differentiating recent from chronic infections has been a long-standing quest in the HIV community. Over the past 15 years, these assays have traditionally measured various HIV-specific antibodies, but recent technological advancements have expanded the diversity of proposed accurate, user-friendly, and financially viable tools. Here we designed a high-throughput genomic HIV incidence assay based on the signature imprinted in the HIV gene sequence population. By combining next-generation sequencing techniques with bioinformatics analysis, we demonstrated that genomic fingerprints are capable of distinguishing recently infected patients from chronically infected patients with high precision. Our high-throughput platform is expected to allow us to process many patients' samples from a single experiment, permitting the assay to be cost-effective for routine surveillance.
    Print ISSN: 0022-538X
    Electronic ISSN: 1098-5514
    Topics: Medicine
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