Effect of a thin AlO_x layer on transition-edge sensor properties

We have studied the physics of transition-edge sensor (TES) devices with an insulating AlOx layer on top of the device to allow implementation of more complex detector geometries. By comparing devices with and without the insulating film, we have observed significant additional noise apparently caused by the insulator layer. In addition, AlOx was found to be a relatively good thermal conductor. This adds an unforeseen internal thermal feature to the system.Comment: 6 pages, 5 figures, Low Temperature Detectors 14 conferenc

Expression of toll-like receptors in non-endemic nasopharyngeal carcinoma

BackgroundNasopharyngeal carcinoma (NPC) is a malignant disease with an enigmatic etiology. NPC associates with Epstein-Barr virus (EBV) and human papillomaviruses (HPVs), while immunological factors also play a role in carcinogenesis. Toll-like receptors (TLRs) are pattern recognition receptors that participate in the immunological defence against pathogens, but their functions are also linked to cancer.MethodsIn our whole population-based study, we retrieved 150 Finnish NPC cases and studied their tumour samples for TLR1, TLR2, TLR4, TLR5, TLR7, and TLR9 expressions by immunohistochemistry, and for the presence of EBV and high-risk HPVs with EBV RNA and HPV E6/E7 mRNA in situ hybridizations. In addition, we analyzed the TLR expression patterns according to age, tumour histology, EBV/HPV status, and outcome.ResultsWe found that all TLRs studied were highly expressed in NPC. Viral status of the tumours varied, and 62% of them were EBV-positive, 14% HPV-positive, and 24% virus-negative. The tumours with strong TLR2(nucl) or TLR5 expression were mostly virus-negative or HPV-positive keratinizing squamous cell carcinomas, and the patients with these tumours were significantly older than those with mild or negative TLR2(nucl)/TLR5 expression. In Kaplan-Meier analysis, the patients with strong TLR5 expression had worse survival compared to the patients with negative or mild TLR5 expression, but the results were linked to other patient and tumour characteristics. In multivariable-adjusted Cox regression analysis, the patients with positive TLR7 tumour expression had better overall survival than those with no TLR7 expression. The 5-year overall survival rates according to TLR7 expression were 66% (mild), 52% (moderate or strong), and 22% (negative).ConclusionsTLRs are highly expressed in non-endemic NPC. Intensity of TLR2 and TLR5 expressions correlate with viral status, and TLR7 seems to be an independent prognostic factor of non-endemic NPC.</p

Machine learning application for prediction of locoregional recurrences in early oral tongue cancer: a Web-based prognostic tool

Estimation of risk of recurrence in early-stage oral tongue squamous cell carcinoma (OTSCC) remains a challenge in the field of head and neck oncology. We examined the use of artificial neural networks (ANNs) to predict recurrences in early-stage OTSCC. A Web-based tool available for public use was also developed. A feedforward neural network was trained for prediction of locoregional recurrences in early OTSCC. The trained network was used to evaluate several prognostic parameters (age, gender, T stage, WHO histologic grade, depth of invasion, tumor budding, worst pattern of invasion, perineural invasion, and lymphocytic host response). Our neural network model identified tumor budding and depth of invasion as the most important prognosticators to predict locoregional recurrence. The accuracy of the neural network was 92.7%, which was higher than that of the logistic regression model (86.5%). Our online tool provided 88.2% accuracy, 71.2% sensitivity, and 98.9% specificity. In conclusion, ANN seems to offer a unique decision-making support predicting recurrences and thus adding value for the management of early OTSCC. To the best of our knowledge, this is the first study that applied ANN for prediction of recurrence in early OTSCC and provided a Web-based tool.</p

Early stage minor salivary gland adenoid cystic carcinoma has favourable prognosis

The purpose of the study was to evaluate the long-term outcome of minor salivary and mucous gland (MiSG) adenoid cystic carcinoma (ACC) of the head and neck and to compare the results with earlier reports including our recently published series on major salivary gland (MaSG) ACC. The study comprised 68 MiSG ACCs operated during 1974-2012 at the Helsinki University Hospital, Helsinki, Finland. Medical records and histological samples were reviewed. Our previously published cohort comprising 54 MaSG ACCs during the years from 1974 to 2009 was used for comparison. The most common locations were the oral cavity and sinonasal cavities. Most patients presented stages IV (33.8%) and I (23.5%) disease. Primary treatment with curative intent, mainly surgery, was offered for 64 patients. Thirty-three (51.6%) of these patients developed a disease recurrence and 22 (66.7%) patients in less than 5 years. The difference in the length of recurrence-free time ( 5 years) had an impact on OS and DSS (p < 0.001) showing worse prognosis for the earlier recurring group. T classes 2-4 (p = 0.005, p < 0.001, and p = 0.001, respectively) and stages II-IV (p = 0.019, p < 0.001, and p = 0.002, respectively) were associated with worse OS, DSS, and DFS. MiSG ACC had a similar long-term survival compared to MaSG ACC. Patients with stage I MiSG ACC seem to carry a favourable prognosis compared with those with stages II, III, and IV tumours. It is thus noteworthy that stage II tumours represent a truly advanced disease entity warranting a more aggressive treatment approach

Clinicopathological characteristics and cell cycle proteins as potential prognostic factors in myoepithelial carcinoma of salivary glands

Myoepithelial carcinoma (MCA) is a rare malignancy of salivary glands that was included in the WHO Classification of Head and Neck Tumors in 1991. MCA has shown a broad spectrum of clinical outcomes, but attempts to identify prognostic markers for this malignancy have not resulted in significant progress. Conventional histopathological characteristics such as tumour grade, nuclear atypia, mitotic index and cell proliferation have failed to predict the outcome of MCA. In this study, we reviewed the histopathology of 19 cases of MCA focusing on nuclear atypia, mitotic count, tumour necrosis, nerve and vascular invasion and occurrence of a pre-existing pleomorphic adenoma in connection to the MCA. Histopathological characteristics and clinical information were correlated with the immunohistochemical expression of cell cycle proteins including c-Myc, p21, Cdk4 and Cyclin D3. The proportion of tumour cells immunoreactive for these markers and their intensity of staining were correlated with clinical information using logistic regression, Kaplan-Meier and Cox regression. Using logistic regression analysis, cytoplasmic c-Myc expression was associated with the occurrence of metastases (P = 0.019), but limitations of semi-quantitation of immunostaining and the limited number of cases preclude definitive conclusions. Our data show that the occurrence of tumour necrosis predicts poor disease-free survival in MCA (P = 0.035).Peer reviewe

Cell-in-cell phenomenon associates with aggressive characteristics and cancer-related mortality in early oral tongue cancer

BackgroundCell-in-cell structures (caused by cell cannibalistic activity) have been related to prognosis of many cancers. This is the first multi-institutional study to assess the prognostic impact of cell-in-cell structures in a large cohort of early oral tongue squamous cell carcinomas (OTSCC).MethodsA total of 308 cases from five Finnish University Hospitals and from the A.C. Camargo Cancer Center, SAo Paulo, Brazil, were included in this study. Cell-in-cell structures were evaluated on surgical postoperative sections that stained with hematoxylin and eosin staining.ResultsWe found that cell-in-cell structures associated with cancer-related mortality in univariable analysis with a hazard ratio (HR) of 2.99 (95%CI 1.52-5.88; P=0.001). This association was confirmed in multivariable analysis (HR 2.22, 95%CI 1.12-4.44; P=0.024). In addition, statistically significant associations were observed between the cell-in-cell structures and other adverse histopathologic characteristics including deep invasion (P< 0.001), high index of tumor budding (P=0.007), worst pattern of invasion (P< 0.001), perineural invasion (P=0.01), and stroma-rich pattern (P=0.001).ConclusionsOur findings demonstrate a significant relationship between cell-in-cell formation and aggressive characteristics of early OTSCC. Cell-in-cell structures have a distinct impact as a novel prognostic indicator in early OTSCC and they can be easily assessed during routine pathology practice

Extracellular Matrix Aggregates from Differentiating Embryoid Bodies as a Scaffold to Support ESC Proliferation and Differentiation

Embryonic stem cells (ESCs) have emerged as potential cell sources for tissue engineering and regeneration owing to its virtually unlimited replicative capacity and the potential to differentiate into a variety of cell types. Current differentiation strategies primarily involve various growth factor/inducer/repressor concoctions with less emphasis on the substrate. Developing biomaterials to promote stem cell proliferation and differentiation could aid in the realization of this goal. Extracellular matrix (ECM) components are important physiological regulators, and can provide cues to direct ESC expansion and differentiation. ECM undergoes constant remodeling with surrounding cells to accommodate specific developmental event. In this study, using ESC derived aggregates called embryoid bodies (EB) as a model, we characterized the biological nature of ECM in EB after exposure to different treatments: spontaneously differentiated and retinoic acid treated (denoted as SPT and RA, respectively). Next, we extracted this treatment-specific ECM by detergent decellularization methods (Triton X-100, DOC and SDS are compared). The resulting EB ECM scaffolds were seeded with undifferentiated ESCs using a novel cell seeding strategy, and the behavior of ESCs was studied. Our results showed that the optimized protocol efficiently removes cells while retaining crucial ECM and biochemical components. Decellularized ECM from SPT EB gave rise to a more favorable microenvironment for promoting ESC attachment, proliferation, and early differentiation, compared to native EB and decellularized ECM from RA EB. These findings suggest that various treatment conditions allow the formulation of unique ESC-ECM derived scaffolds to enhance ESC bioactivities, including proliferation and differentiation for tissue regeneration applications. © 2013 Goh et al

High tumor mutation burden predicts favorable outcome among patients with aggressive histological subtypes of lung adenocarcinoma: A population-based single-institution study

Objectives: Tumor mutation burden (TMB) is an emerging predictive cancer biomarker. Few studies have addressed the prognostic role of TMB in non-small cell lung carcinoma, with conflicting results. Moreover, the association of TMB with different histological subtypes of lung adenocarcinoma has hitherto not been systematically evaluated. Here we studied the prognostic value of TMB and its distribution in different histological subtypes of lung adenocarcinomas in a retrospective cohort using the most recent updated classification guidelines.Materials and methods: 176 surgically resected stage I-IV lung adenocarcinomas were histologically reclassified according to WHO 2015 guidelines. A modified classification subdividing the acinar subtype into classic acinar, complex glandular and cribriform subtypes was further applied and potentially prognostic histopathological characteristics such as tumor-infiltrating lymphocytes were evaluated. 148 patients with stage I-III tumors and complete follow-up data were included in the survival analyses. TMB was determined by a commercial next generation sequencing panel from 131 tumors, out of which 105 had survival data available.Results: Predominant micropapillary, solid and complex glandular as well as nonpredominant cribriform histological subtypes were associated with significantly shorter survival. High TMB concentrated in micropapillary, solid and acinar predominant subtypes. Interestingly, TMB >= 14 mutations/MB conferred a stage- and histology-independent survival benefit compared to TMB < 14 in multivariable analysis for overall (HR 0.284, 95% CI 0.14-0.59, P=0.001) and disease-specific survival (HR 0.213, 95% CI 0.08-0.56, P=0.002).Conclusion: TMB was an independent biomarker of favorable prognosis in our cohort of lung adenocarcinoma despite being associated with predominant histological subtypes considered aggressive

Yhtenäiset vaatimukset lääketieteen ja hammaslääketieteen tohtorintutkinnolle Suomessa

Oulussa järjestettiin 13.6.2018 lääketieteen ja hammaslääketieteen tohtorintutkinnon konsensuskokous, jossa käytiin läpi vallitsevia käytäntöjä ja muutostarpeita. Ohjeellinen tutkinnon laajuus on neljä vuotta kokopäiväistä työtä, ja muodollisesti tutkinnon myöntää yhtä yliopistoa lukuun ottamatta aina vastaava tiedekunta. Ohjaajia on tyypillisesti kahdesta kolmeen, ja yksi on pääohjaaja. Seurantaryhmä on käytössä tai ollaan ottamassa käyttöön kaikissa yliopistoissa. Aktiivinen seurantaryhmä tukee merkittävästi ohjausprosessia. Väitöskirjojen asiantuntijoina toimivat esitarkastajat ja vastaväittäjät ovat yleensä muualta kuin suorituspaikan yliopistosta. Osittain tästä syystä suuria eroja eri yliopistojen tohtorintutkinnon vaatimusten välillä ei todettu. Haasteena väitöskirjatyössä on kliinisen työn paine ja nuorten kollegoiden ruuhkavuosien kuormittuminen, mitkä heikentävät mahdollisuuksia tutkimustyöhön. Myönteisiä muutoksia ovat olleet tohtoriopintojen systematisoituminen sekä ohjaamisen tason ja väitöskirjantekijöiden tuen paraneminen. Kaikki osallistuneet kannattivat käytäntöjen vakiinnuttamista ja yhtenäistämistä säännöllisellä konsensuskokoustyöskentelyllä.</p

Tissue distribution of the laminin β1 and β2 chain during embryonic and fetal human development

Laminins are the major glycoproteins present in all basement membranes. Previously, we showed that perlecan is present during human development. Although an overview of mRNA-expression of the laminin β1 and β2 chains in various developing fetal organs is already available, a systematic localization of the laminin β1 and β2 chains on the protein level during embryonic and fetal human development is missing. Therefore, we studied the immunohistochemical expression and tissue distribution of the laminin β1 and β2 chains in various developing embryonic and fetal human organs between gestational weeks 8 and 12. The laminin β1 chain was ubiquitously expressed in the basement membrane zones of the brain, ganglia, blood vessels, liver, kidney, skin, pancreas, intestine, heart and skeletal system. Furthermore, the laminin β2 chain was present in the basement membrane zones of the brain, ganglia, skin, heart and skeletal system. The findings of this study support and expand upon the theory that these two laminin chains are important during human development