DICER1-Mutated Botryoid Fibroepithelial Polyp of the Parotid Duct: Report of the First Case

DICER1, a member of the ribonuclease III family, is involved in the biogenesis of microRNAs and, hence, it influences gene expression regulation. DICER1 germline (associated with the inherited DICER1 syndrome) or somatic mutations have been linked to tumorigenesis in histogenetically diverse benign and malignant neoplasms in different organs including pleuropulmonary blastoma, cystic nephroma, embryonal rhabdomyosarcoma, nasal chondromesenchymal hamartoma, poorly differentiated thyroid carcinoma, thyroblastoma, intracranial sarcoma and gonadal Sertoli-Leydig cell tumors in addition to others. Moreover, rare botryoid (giant) fibroepithelial polyps may harbor this mutation. Herein, we describe the first reported case of a DICER1-mutated botryoid fibroepithelial polyp occurring within the parotid duct of a 65-year-old female who has no other features or family history of the DICER1 syndrome. Based on its distinctive morphology, we tested this lesion specifically for DICER1 mutations and confirmed the presence of a pathogenic DICER1 variant with a low allele frequency, consistent with a somatic mutation

Innovative, effective and sustainable technology and logistics for forest residual biomass

Luken kirjat, raportit, oppaat ja esitteet. Summary of the INFRES project results201

Differentiation of benign and malignant vertebral fractures using a convolutional neural network to extract CT-based texture features.

PURPOSE To assess the diagnostic performance of three-dimensional (3D) CT-based texture features (TFs) using a convolutional neural network (CNN)-based framework to differentiate benign (osteoporotic) and malignant vertebral fractures (VFs). METHODS A total of 409 patients who underwent routine thoracolumbar spine CT at two institutions were included. VFs were categorized as benign or malignant using either biopsy or imaging follow-up of at least three months as standard of reference. Automated detection, labelling, and segmentation of the vertebrae were performed using a CNN-based framework ( https://anduin.bonescreen.de ). Eight TFs were extracted: Varianceglobal, Skewnessglobal, energy, entropy, short-run emphasis (SRE), long-run emphasis (LRE), run-length non-uniformity (RLN), and run percentage (RP). Multivariate regression models adjusted for age and sex were used to compare TFs between benign and malignant VFs. RESULTS Skewnessglobal showed a significant difference between the two groups when analyzing fractured vertebrae from T1 to L6 (benign fracture group: 0.70 [0.64-0.76]; malignant fracture group: 0.59 [0.56-0.63]; and p = 0.017), suggesting a higher skewness in benign VFs compared to malignant VFs. CONCLUSION Three-dimensional CT-based global TF skewness assessed using a CNN-based framework showed significant difference between benign and malignant thoracolumbar VFs and may therefore contribute to the clinical diagnostic work-up of patients with VFs

Productivity in the Financial Services Sector

On 11-12 November 2008, SUERF and Banque Centrale du Luxembourg organized a conference on Productivity in the Financial Services Sector on the occasion of the tenth anniversary of the Banque Centrale du Luxembourg. The conference addressed three main themes: first, stylized facts on banks' productivity developments and the measurement of productivity; second, sources of productivity in banking; and third, the possible repercussions and consequences of the financial crisis on financial institutions' future productivity development. These three topics are taken up from various angles in the papers contained in the present volume, which represent a selection of the papers presented at the conference. Coming back to the three themes mentioned at the outset, the conference yielded some interesting results and raised many issues for further research. As regards theme 1, the papers presented overall suggest that financial integration in Europe has brought some, albeit according to some studies limited, convergence of bank efficiency among countries but on average productivity improvement has been weak. Various interesting attempts to capture banks' output were presented, but the various performance and efficiency measures yield different results. Linked to the difficulty of measuring the value of financial institutions' services, it remains far from clear what the "fair value" of a bank should be. This problem may also in part explain the very sharp ups and downs of bank stocks recently. Concerning theme 2, sources of productivity in financial services, several potentially important factors were mentioned: investments in ICT, investments in human resources, the quality of managers and remuneration policy, process effectiveness, mergers and acquisitions and economies of scale, privatizations, risk diversification versus regional and/or product specialisation, and risk-taking. Yet, no unambiguous picture emerged on which of these factors are most important. Regarding theme 3, the financial crisis may have far-reaching implications on our view of financial innovation and efficiency, on the way how to measure productivity appropriately as well as on the future development of financial institutions' productivity. First, the question arises whether the quest for productivity and profitability may under certain circumstances compromise the quality of banks' services (such as, e.g. the care invested into credit assessments and risk monitoring) and as a consequence put the stability of banks and the financial system at risk. As the recent crisis and its underlying causes suggest, there may at times be trade-offs between innovation and financial stability. If financial supervision and risk management do not keep up with financial innovation, the social value of such innovation may not be positive at all times. Financial innovation may also have blurred signals on banks? financial and risk positions, and thus have misled bank shareholders, clients and supervisors in their assessment of banks? business models and conduct of business. Second, the crisis might also affect banks? future performance: Increased government interference and stricter surveillance and capital adequacy rules might curb banks? profitability and efficiency, as measured by traditional performance indicators. However, the conventional measures of performance as presented and discussed at the conference - however varied and multifaceted they may be in trying to measure efficieny (i.e. the avoidance of unnecessary costs in the production process) and competition (the avoidance of inappropriately high profits) - basically seem to have a short-term focus. A longer-term perspective would also consider e.g. the financial institutions? solvency and the safety of deposits, as well as their stability and continued performance in periods of severe stress. Such extensions to the concept of ?performance? should certainly be explored more deeply in the light of the current crisis. In particular, bank efficiency should be considered by supervisors with a view to its influence on risk behaviour. The current debate on regulatory reform in response to the crisis also addresses the need for closer international coordination among supervisory regimes. Tighter regulatory coordination may, on the one hand, close regulatory loopholes, thus curbing banks? profit opportunities, at least in the short run. On the other hand, international harmonization of regulatory rules may generate considerable cost savings for internationally active financial institutions. By contributing to financial market integration it could also stiffen competition and in this way improve efficiency. A related issue is how the crisis will affect the size of banks in the future. Will consolidation in the sector ultimately result in fewer and bigger banks? Or will governments? and regulators? bad experience with institutions which are ?too big to fail? create pressure towards more and smaller institutions? The outcome of this may in turn have possible implications for competition and thus, ultimately, on future innovation, efficiency and productivity developments. Finally, in the coming months and years the issue of exit strategies from state intervention will have to be solved. In particular, how long should partial or full nationalisations of troubled banks last? Historical experiences vary, ranging from rather rapid re-privatisations in some cases to continued strong government influence decades. How can banks? increased reliance on government assistance be abolished and market-based incentives for productivity-enhancing strategies be restored, given the massive moral hazard created by the ? unavoidable ? government bail outs of banks? In conclusion, the conference demonstrated that various disciplines ? business administration, management, organisation and economics ? as well as different professional perspectives ? those of academia, practitioners and of policy makers ? need to be combined to do full justice to the complexity of the subject at hand. SUERF?s triple constituency and multiple-discipline approach again proved particularly suitable to approaching such a far-reaching topic

Expression of the Arabidopsis redox-related LEA protein, SAG21 is regulated by ERF, NAC and WRKY transcription factors

SAG21/LEA5 is an unusual late embryogenesis abundant protein in Arabidopsis thaliana, that is primarily mitochondrially located and may be important in regulating translation in both chloroplasts and mitochondria. SAG21 expression is regulated by a plethora of abiotic and biotic stresses and plant growth regulators indicating a complex regulatory network. To identify key transcription factors regulating SAG21 expression, yeast-1-hybrid screens were used to identify transcription factors that bind the 1685 bp upstream of the SAG21 translational start site. Thirty-three transcription factors from nine different families bound to the SAG21 promoter, including members of the ERF, WRKY and NAC families. Key binding sites for both NAC and WRKY transcription factors were tested through site directed mutagenesis indicating the presence of cryptic binding sites for both these transcription factor families. Co-expression in protoplasts confirmed the activation of SAG21 by WRKY63/ABO3, and SAG21 upregulation elicited by oligogalacturonide elicitors was partially dependent on WRKY63, indicating its role in SAG21 pathogen responses. SAG21 upregulation by ethylene was abolished in the erf1 mutant, while wound-induced SAG21 expression was abolished in anac71 mutants, indicating SAG21 expression can be regulated by several distinct transcription factors depending on the stress condition

Molecular Subtyping of Invasive Breast Cancer Using a PAM50-Based Multigene Expression Test-Comparison with Molecular-Like Subtyping by Tumor Grade/Immunohistochemistry and Influence on Oncologist’s Decision on Systemic Therapy in a Real-World Setting

In intermediate risk hormone receptor (HR) positive, HER2 negative breast cancer (BC), the decision regarding adjuvant chemotherapy might be facilitated by multigene expression tests. In all, 142 intermediate risk BCs were investigated using the PAM50-based multigene expression test Prosigna® in a prospective multicentric study. In 119/142 cases, Prosigna® molecular subtyping was compared with local and two central (C1 and C6) molecular-like subtypes relying on both immunohistochemistry (IHC; HRs, HER2, Ki-67) and IHC + tumor grade (IHC+G) subtyping. According to local IHC, 35.4% were Luminal A-like and 64.6% Luminal B-like subtypes (local IHC+G subtype: 31.9% Luminal A-like; 68.1% Luminal B-like). In contrast to local and C1 subtyping, C6 classified >2/3 of cases as Luminal A-like. Pairwise agreement between Prosigna® subtyping and molecular-like subtypes was fair to moderate depending on molecular-like subtyping method and center. The best agreement was observed between Prosigna® (53.8% Luminal A; 44.5% Luminal B) and C1 surrogate subtyping (Cohen’s kappa = 0.455). Adjuvant chemotherapy was suggested to 44.2% and 88.6% of Prosigna® Luminal A and Luminal B cases, respectively. Out of all Luminal A-like cases (locally IHC/IHC+G subtyping), adjuvant chemotherapy was recommended if Prosigna® testing classified as Prosigna® Luminal A at high / intermediate risk or upgraded to Prosigna® Luminal B

Covid-19 triage in the emergency department 2.0: how analytics and AI transform a human-made algorithm for the prediction of clinical pathways

The Covid-19 pandemic has pushed many hospitals to their capacity limits. Therefore, a triage of patients has been discussed controversially primarily through an ethical perspective. The term triage contains many aspects such as urgency of treatment, severity of the disease and pre-existing conditions, access to critical care, or the classification of patients regarding subsequent clinical pathways starting from the emergency department. The determination of the pathways is important not only for patient care, but also for capacity planning in hospitals. We examine the performance of a human-made triage algorithm for clinical pathways which is considered a guideline for emergency departments in Germany based on a large multicenter dataset with over 4,000 European Covid-19 patients from the LEOSS registry. We find an accuracy of 28 percent and approximately 15 percent sensitivity for the ward class. The results serve as a benchmark for our extensions including an additional category of palliative care as a new label, analytics, AI, XAI, and interactive techniques. We find significant potential of analytics and AI in Covid-19 triage regarding accuracy, sensitivity, and other performance metrics whilst our interactive human-AI algorithm shows superior performance with approximately 73 percent accuracy and up to 76 percent sensitivity. The results are independent of the data preparation process regarding the imputation of missing values or grouping of comorbidities. In addition, we find that the consideration of an additional label palliative care does not improve the results

Behavioral genomics of honeybee foraging and nest defense

The honeybee has been the most important insect species for study of social behavior. The recently released draft genomic sequence for the bee will accelerate honeybee behavioral genetics. Although we lack sufficient tools to manipulate this genome easily, quantitative trait loci (QTLs) that influence natural variation in behavior have been identified and tested for their effects on correlated behavioral traits. We review what is known about the genetics and physiology of two behavioral traits in honeybees, foraging specialization (pollen versus nectar), and defensive behavior, and present evidence that map-based cloning of genes is more feasible in the bee than in other metazoans. We also present bioinformatic analyses of candidate genes within QTL confidence intervals (CIs). The high recombination rate of the bee made it possible to narrow the search to regions containing only 17–61 predicted peptides for each QTL, although CIs covered large genetic distances. Knowledge of correlated behavioral traits, comparative bioinformatics, and expression assays facilitated evaluation of candidate genes. An overrepresentation of genes involved in ovarian development and insulin-like signaling components within pollen foraging QTL regions suggests that an ancestral reproductive gene network was co-opted during the evolution of foraging specialization. The major QTL influencing defensive/aggressive behavior contains orthologs of genes involved in central nervous system activity and neurogenesis. Candidates at the other two defensive-behavior QTLs include modulators of sensory signaling (Am5HT(7) serotonin receptor, AmArr4 arrestin, and GABA-B-R1 receptor). These studies are the first step in linking natural variation in honeybee social behavior to the identification of underlying genes