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Purpose: Pancreatic cancer (PDAC) is characterized by infiltrative, spiculated tumor growth into the surrounding non-neoplastic tissue. Clinically, its diagnosis is often established by magnetic resonance imaging (MRI). At the invasive margin, tumor buds can be detected by histology, an established marker associated with poor prognosis in different types of tumors. Methods: We analyzed PDAC by determining the degree of tumor spiculation on T2-weighted MRI using a 3-tier grading system. The grade of spiculation was correlated with the density of tumor buds quantified in histological sections of the respective surgical specimen according to the guidelines of the International Tumor Budding Consensus Conference (n = 28 patients). Results: 64% of tumors revealed intermediate to high spiculation on MRI. In over 90% of cases, tumor buds were detected. We observed a significant positive rank correlation between the grade of radiological tumor spiculation and the histopathological number of tumor buds (rs = 0.745, p < 0.001). The number of tumor buds was not significantly associated with tumor stage, presence of lymph node metastases, or histopathological grading (p ≥ 0.352). Conclusion: Our study identifies a readily available radiological marker for non-invasive estimation of tumor budding, as a correlate for infiltrative tumor growth. This finding could help to identify PDAC patients who might benefit from more extensive peripancreatic soft tissue resection during surgery or stratify patients for personalized therapy concepts. [ABSTRACT FROM AUTHOR]

Advances in the application of polymers for electrochemical cells require an understanding of their viscous deformation mechanisms and their interaction with moisture. Nanoindentation offers a localized, microscale testing alternative to traditional tensile testing. However, the viscoelastic nature of the polymers, combined with their increased compliance, presents challenges in the analysis of nanoindentation results. In addition, the dependence on moisture results in significant scatter and low repeatability. This study combines nanoindentation and tensile testing as a verification method and compares different correction protocols for static nanoindentation to investigate the mechanical behavior of polymer electrolyte membranes. Comparisons of different indentation devices, analysis methods, and indentation protocols show a significant overestimation of Young's modulus using the classical Oliver–Pharr method compared to values determined from tensile tests. Nanoindentation at different humidity levels revealed different mechanisms leading to a decrease in Young's modulus and hardness with increasing humidity. [ABSTRACT FROM AUTHOR]

Autopsy rates are declining, while major discrepancies between autopsies and clinical diagnoses remain. Still, little is known about the impact of suspected underlying diseases, for example, a diagnosis of cancer, on the autopsy rate. The aim of this study was to investigate the relation between the clinical cause of death, a history of cancer, and the medical autopsy rate using data from the Netherlands Cohort Study on Diet and Cancer (NLCS), a large prospective cohort study with a long follow-up. The NLCS is a prospective study initiated in 1986 and includes 120,852 persons (58,279 males and 62,573 females), 55–69 years of age at the time of enrollment. The NLCS was linked with the Dutch Nationwide Pathology Databank (PALGA), the Dutch Population Register (GBA), the Netherlands Cancer Registry, and the causes of death registry (Statistics Netherlands). If applicable, the 95% confidence intervals were calculated. During the follow-up of the NLCS, 59,760 deaths were recorded by linkage with the GBA from 1991 until 2009. Of these, a medical autopsy was performed on 3736 deceased according to linkage with PALGA, resulting in an overall autopsy rate of 6.3%. Major variations in the autopsy rate were observed according to the cause of death. The autopsy rate increased according to the number of contributing causes of death. Lastly, a diagnosis of cancer affected the autopsy rate. The clinical cause of death and a history of cancer both influenced the medical autopsy rate in a large national cohort. The insight this study provides may help clinicians and pathologists counteracting the further downfall of the medical autopsy. [ABSTRACT FROM AUTHOR]

Knee osteoarthritis is a leading cause of chronic disability and economic burden. In many patients who are not surgical candidates, existing treatment options are insufficient. Clinical evidence for a new treatment approach, genicular artery embolisation (GAE), is currently limited to single arm cohort, or small population randomised studies. This trial will investigate the use of a permanent embolic agent for embolisation of abnormal genicular arterial vasculature to reduce pain in patients with mild to moderate knee osteoarthritis. Up to 110 participants, 45 years or older, with knee pain for ≥ 3 months resistant to conservative treatment will be randomised (1:1) to GAE or a sham procedure. The treatment group will receive embolisation using 100-micron Embozene™ microspheres (Varian, a Siemens Healthineers Company) (investigational use for this indication in the UK), and the sham group will receive 0.9% saline in an otherwise identical procedure. Patients will be followed for 24 months. At 6 months, sham participants will be offered crossover to GAE. The primary endpoint is change of 4 Knee Injury and OA Outcome Score subscales (KOOS4) at 6 months post-randomisation. The study will also evaluate quality of life, health economics, imaging findings, and psychosocial pain outcomes. The primary manuscript will be submitted for publication after all participants complete 6 months of follow-up. The trial is expected to run for 3.5 years. Trial Registration: ClinicalTrials.gov, Identifier: NCT05423587. [ABSTRACT FROM AUTHOR]

The anticanonical complex generalizes the Fano polytope from toric geometry and has been used to study Fano varieties with torus action so far. We provide an explicit description of the anticanonical complex for complete intersections in toric varieties defined by non-degenerate systems of Laurent polynomials. As an application, we classify the terminal Fano threefolds that are embedded into a fake weighted projective space via a general system of Laurent polynomials. [ABSTRACT FROM AUTHOR]

The ability to image human tissue samples in 3D, with both cellular resolution and a large field of view (FOV), can improve fundamental and clinical investigations. Here, we demonstrate the feasibility of light-sheet imaging of ~5 cm3 sized formalin fixed human brain and up to ~7 cm3 sized formalin fixed paraffin embedded (FFPE) prostate cancer samples, processed with the FFPE-MASH protocol. We present a light-sheet microscopy prototype, the cleared-tissue dual view Selective Plane Illumination Microscope (ct-dSPIM), capable of fast 3D high-resolution acquisitions of cm3 scale cleared tissue. We used mosaic scans for fast 3D overviews of entire tissue samples or higher resolution overviews of large ROIs with various speeds: (a) Mosaic 16 (16.4 µm isotropic resolution, ~1.7 h/cm3), (b) Mosaic 4 (4.1 µm isotropic resolution, ~ 5 h/cm3) and (c) Mosaic 0.5 (0.5 µm near isotropic resolution, ~15.8 h/cm3). We could visualise cortical layers and neurons around the border of human brain areas V1&V2, and could demonstrate suitable imaging quality for Gleason score grading in thick prostate cancer samples. We show that ct-dSPIM imaging is an excellent technique to quantitatively assess entire MASH prepared large-scale human tissue samples in 3D, with considerable future clinical potential. A light-sheet microscopy prototype, the cleared-tissue dual view Selective Plane Illumination Microscope (ct-dSPIM), is presented and shown to enable quantitative assessment of large-scale human tissue samples in 3D with clinical potential. [ABSTRACT FROM AUTHOR]

Gelatinous animals have been historically viewed as trophic dead-ends. However, there are increasing data showing these organisms being consumed by diverse predators and demonstrate they play an important role in ecosystem functioning. Here we document the Ocypode quadrata (Fabricius, 1787) scavenging on stranded Physalia physalis (Linnaeus, 1758) at Sergipe and Bahia, tropical Brazil (11° and 14° Lat. S), based on Instagram® posts. These findings highlight the potential of social media to complement the information provided by traditional academic sources. We also suggest that this predatory interaction is probably more common than reported in the literature, perhaps due to methodological constraints of stomach content analyses, which may overlook the consumption of gelatinous animals by ghost crabs. [ABSTRACT FROM AUTHOR]

Dermal substitutes must be flexible, degrade rapidly and stimulate the growth of new dermis preventing fibrosis formation. Bioreabsorbable polymers, such as poly (d,l lactic-co-glycolic) (PDLGA) do not stimulate tissue growth, but when associated with inductive molecules or cells, it can provide tissue repair. In this study, PDLGA (67:23) membranes were synthetized and to verify its degradation properties, it was analyzed before and after cell culture. Dynamic mechanical analysis showed that the copolymer presented force and deformation features desired as a dermal substitute. Early degradation after 7 days was shown by thermal and morphological analysis. The recent isolated adipose-derived mesenchymal stem cells, known to modulate scar and fibrosis formation, seeded in PDLGA membranes remained phenotypically undifferentiated. The fast degradation rate and the properties to support cell survival, directs to the PDLGA essential properties as a candidate for a polymer-cell construct, focused to modulate skin repair. [ABSTRACT FROM AUTHOR]

Background In Germany, one of eight people over 40 suffer from COPD, and the trend is rising. COPD combines chronic bronchitis and emphysema with or without obstruction. In family practice, COPD and asthma are the two most frequent respiratory diseases. Search methods This continuing educational article is based on the National Disease Guideline for Asthma and the addendum of 2020, which are supplemented by findings from special investigations and past publications by the author. Main messages Unfortunately, COPD often is discovered rather late at an advanced stage. The typical symptoms of coughing, sputum or shortness of breath might have been neglected or interpreted as being part of a normal aging process. Carefully drawing on a patient's medical history and lung function testing with a bronchodilator test, a diagnosis for COPD can be established and differentiated from asthma. The treatment is purely symptomatic in nature and the goal is to reduce symptoms and potential exacerbations. The approach is based on four pillars: the elimination of noxae - still the most effective approach - infection prophylaxis, rehabilitation and treatment with medication. For the inhalation-therapy, bronchodilators, muscarinic and beta agonists are available, short-acting agonists for on-demand therapy and long-acting agonists for long-term therapy. Both types of bronchodilators are equally capable to reduce exacerbations. Under these conditions, the necessity to administer inhaled corticosteroids (ICS) remains limited to the few cases in which exacerbations still occur despite dual bronchodilation. A slight exacerbation can be adjusted by the trained patient on his own by increasing the dose of his medication. In case if a severe exacerbation can be treated on an outpatient basis, a short-term oral glucocorticoid therapy is used as an initial treatment. An antibiotic is only recommended in case of purulent sputum. Conclusions If early signs are recognized and a patient's medical history is carefully evaluated, a COPD can be earlier confirmed . The long-term therapy with bronchodilators facilitates to relieve symptoms and reduce exacerbations, so ICS have to be used only as an exception. [ABSTRACT FROM AUTHOR]

Background* In Germany, 5 % of the population is suffering from Asthma which is, alongside COPD, the most common chronic respiratory disease encountered in family medicine and the most common chronic disease in pediatric practice. Search methods This continuing educational article is based on the National Disease Guideline for Asthma and the addendum of 2020, which are supplemented by findings from special investigations and past publications by the author who is an expert for respiratory diseases working in family medicine. Key messages Based on a careful medical history and considering a thoughtful differential diagnosis, the diagnosis for asthma can be established in a relatively safe manner and confirmed by pulmonary function testing including a bronchodilator test. Alternatively, and in exceptional cases, peak-flow measurement and/or the measuring of exhaled nitrogen oxide can be helpful. First and foremost, the therapy consists of an inhalation of a corticosteroid taken alone or in combination with a long-acting betaagonist. This anti-inflammatory therapy is able to prevent a remodeling, i.e., the destruction of the mucous membrane, a thickening of the basal membrane or a hypertrophy of the bronchial muscles and the development of a functional obstruction. In case of an insufficient effect, long-acting muscarinic antagonists or leukotriene antagonists can be added; also, if necessary, biologicals can be contemplated. A long-term treatment with oral corticosteroids should be avoided, if possible. Conclusions Given an early diagnosis and correct treatment, the vast majority of asthmatics can lead a life without symptoms or, at worst, experience temporary mild symptoms. A prerequisite is a sufficiently assessed anti-inflammatory therapy, which must be regularly adapted to the current severity and which the patient carries out regularly and correctly. [ABSTRACT FROM AUTHOR]

The wake-active orexin system plays a central role in the dynamic regulation of glucose homeostasis. Here we show orexin receptor type 1 and 2 are predominantly expressed in dorsal raphe nucleus-dorsal and -ventral, respectively. Serotonergic neurons in ventral median raphe nucleus and raphe pallidus selectively express orexin receptor type 1. Inactivation of orexin receptor type 1 in serotonin transporter-expressing cells of mice reduced insulin sensitivity in diet-induced obesity, mainly by decreasing glucose utilization in brown adipose tissue and skeletal muscle. Selective inactivation of orexin receptor type 2 improved glucose tolerance and insulin sensitivity in obese mice, mainly through a decrease in hepatic gluconeogenesis. Optogenetic activation of orexin neurons in lateral hypothalamus or orexinergic fibers innervating raphe pallidus impaired or improved glucose tolerance, respectively. Collectively, the present study assigns orexin signaling in serotonergic neurons critical, yet differential orexin receptor type 1- and 2-dependent functions in the regulation of systemic glucose homeostasis. The wake-active orexin system plays a central role in the dynamic regulation of glucose homeostasis. Here the authors report that inactivation of the orexin receptor type 1 or 2 in serotonergic neurons differentially regulate systemic glucose homeostasis in the context of diet induced obesity. [ABSTRACT FROM AUTHOR]

Over the past decades, melanoma-related mortality has remained nearly stable. The main reason is treatment failure of metastatic disease and the inherently linked knowledge gap regarding metastasis formation. In order to elicit invasion, melanoma cells manipulate the tumor microenvironment, gain motility, and adhere to the extracellular matrix and cancer-associated fibroblasts. Melanoma cells thereby express different cell adhesion molecules like laminins, integrins, N-cadherin, and others. Epithelial-mesenchymal transition (EMT) is physiological during embryologic development, but reactivated during malignancy. Despite not being truly epithelial, neural crest-derived malignancies like melanoma share similar biological programs that enable tumorigenesis, invasion, and metastasis. This complex phenomenon is termed phenotype switching and is intertwined with oncometabolism as well as dormancy escape. Additionally, it has been shown that primary melanoma shed exosomes that create a favorable premetastatic niche in the microenvironment of secondary organs and lymph nodes. Although the growing body of literature describes the aforementioned concepts separately, an integrative holistic approach is missing. Using melanoma as a tumor model, this review will shed light on these complex biological principles in an attempt to clarify the mechanistic metastatic pathways that dictate tumor and patient fate. [ABSTRACT FROM AUTHOR]

The article "COPD - from early and accurate diagnosis to correct therapy without frequent use of corticosteroids" by Thomas Hausen is criticized for losing the critical perspective of general practitioners. The author emphasizes the importance of early diagnosis of COPD but notes that there is no therapy beyond symptom relief. The article is criticized for lacking evidence for certain statements, and it is pointed out that vaccination against pneumococcal is not sufficiently secured. Letters to the editor regarding a continuing education article on COPD in the Journal of General Medicine contain positive feedback from readers who found the article understandable and practical. It is emphasized that general practitioners can play an important role in the early detection of COPD and that eliminating harmful toxins is the most effective way to influence the course of the disease. [Extracted from the article]

Paclitaxel use in cancer treatment is limited by a painful syndrome that has no effective treatment. Despite new therapies, drugs of the World Health Organization (WHO) analgesic ladder remain a useful therapeutic tool for cancer pain relief. Since cancer pain is caused by both tumor and chemotherapy, we assessed the efficacy of drugs from the WHO analgesic ladder for cancer pain relief in a paclitaxel-induced pain syndrome (P-IPS) model. P-IPS was induced in rats by one or four injections of paclitaxel on alternate days. The acute and chronic phases were assessed 24 h and 15 days after the first paclitaxel injection, respectively. The mechanical allodynia was evaluated after (step 1 of the ladder) paracetamol, (step 2) codeine alone or plus paracetamol and (step 3) morphine treatment in the acute or chronic phase of P-IPS. Paracetamol, codeine and morphine were equally efficacious in reducing the acute phase of the P-IPS. Codeine plus paracetamol had similar efficacy and potency when administered together in the acute phase of the P-IPS, but produced a longer-lasting effect than when separately managed. Moreover, paracetamol, codeine and morphine partially reduced the chronic phase of P-IPS, losing their efficacy and, in the case of codeine, potency when compared to the acute phase. However, paracetamol plus codeine increased the potency and efficacy of the codeine when compared to codeine administered alone in the chronic phase of P-IPS, producing a long-lasting anti-allodynic effect. Together, analgesics of WHO analgesic ladder reduce both acute and chronic phases of P-IPS, with codeine plus paracetamol presenting more potent, efficacious and long-lasting effect. Thus, in addition to tumor pain, drugs of WHO analgesics ladder could also be useful to treat P-IPS. [ABSTRACT FROM AUTHOR]

The development of new technologies to produce three-dimensional and biocompatible scaffolds associated with high-end cell culture techniques have shown to be promising for the regeneration of tissues and organs. Some biomedical devices, as meniscus prosthesis, require high flexibility and tenacity and such features are found in polyurethanes which represent a promising alternative. The Poly(PCL–TMC)urethane here presented, combines the mechanical properties of PCL with the elasticity attributed by TMC and presents great potential as a cellular carrier in cartilage repair. Scanning electron microscopy showed the presence of interconnected pores in the three-dimensional structure of the material. The scaffolds were submitted to proliferation and cell differentiation assays by culturing mesenchymal stem cells in bioreactor. The tests were performed in dynamic flow mode at the rate of 0.4 mL/min. Laser scanning confocal microscopy analysis showed that the flow rate promoted cell growth and cartilage ECM synthesis of aggrecan and type II collagen within the Poly(PCL–TMC)urethane scaffolds. This study demonstrated the applicability of the polymer as a cellular carrier in tissue engineering, as well as the ECM was incremented only when under oriented flow rate stimuli. Therefore, our results may also provide data on how oriented flow rate in dynamic bioreactors culture can influence cell activity towards cartilage ECM synthesis even when specific molecular stimuli are not present. This work addresses new perspectives for future clinical applications in cartilage tissue engineering when the molecular factors resources could be scarce for assorted reasons. [ABSTRACT FROM AUTHOR]

While intensive efforts have been devoted to studying the nature of the solid-electrolyte interphase (SEI), little attention has been paid to understanding its role in the mechanical failures of electrodes. Here we unveil the impact of SEI inhomogeneities on early-stage defect formation in Si electrodes. Buried under the SEI, these early-stage defects are inaccessible by most surface-probing techniques. With operando full field diffraction X-ray microscopy, we observe the formation of these defects in real time and connect their origin to a heterogeneous degree of lithiation. This heterogeneous lithiation is further correlated to inhomogeneities in topography and lithium-ion mobility in both the inner- and outer-SEI, thanks to a combination of operando atomic force microscopy, electrochemical strain microscopy and sputter-etched X-ray photoelectron spectroscopy. Our multi-modal study bridges observations across the multi-level interfaces (Si/LixSi/inner-SEI/outer-SEI), thus offering novel insights into the impact of SEI homogeneities on the structural stability of Si-based lithium-ion batteries. Severe structural deformation during (de)lithiation is the main factor limiting the stability of Si anodes in Li-ion batteries. Here, a multi-modal approach is used to visualize these deformations in their early-stage and link them to inhomogeneities in the dual-layer solid-electrolyte interphase. [ABSTRACT FROM AUTHOR]

Very high theoretical specific energies and abundant resource availability have emerged interest in primary Si–air batteries during the last decade. When operated with highly doped Si anodes and EMIm(HF)2.3F ionic liquid electrolyte, specific energies up to 1660 Wh kgSi−1 can be realized. Owing to their high-discharge voltage, the most investigated anode materials are ⟨ 100 ⟩ oriented highly As-doped Si wafers. As there is substantial OCV corrosion for these anodes, the most favorable mode of operation is continuous discharge. The objective of the present work is, therefore, to investigate the discharge behavior of cells with ⟨ 100 ⟩ As-doped Si anodes and to compare their performance to cells with ⟨ 100 ⟩ B-doped Si anodes under pulsed discharge conditions with current densities of 0.1 and 0.3 mA cm−2. Nine cells for both anode materials were operated for 200 h each, whereby current pulse time related to total operating time ranging from zero (OCV) to one (continuous discharge), are considered. The corrosion and discharge behavior of the cells were analyzed and anode surface morphologies after discharge were characterized. The performance is evaluated in terms of specific energy, specific capacity, and anode mass conversion efficiency. While for high-current pulse time fractions, the specific energies are higher for cells with As-doped Si anodes, along with low-current pulse fractions the cells with B-doped Si anodes are more favorable. It is demonstrated, that calculations for the specific energy under pulsed discharge conditions based on only two measurements—the OCV and the continuous discharge—match very well with the experimental data. [ABSTRACT FROM AUTHOR]

Objective: Autopsy rates have been declining worldwide. The present study reports the outcome of a retrospective analysis of all non-forensic autopsies in the Netherlands over a course of 25 years, and compares these with the most recent Dutch study. Method: Retrospectively, 25 years of data on clinical autopsies from the Nationwide Network and Registry of Histo- and Cytopathology in the Netherlands (PALGA) was paired with the mortality registry (Statistics Netherlands). Results: The crude prevalence of autopsies declined from 7.07% in 1991 to 2.73% in 2015. After adjusting for age at death, there was no difference in autopsy rate between males and females. An increasing age significantly decreased the autopsy rate. Conclusion: In the Netherlands, clinical autopsies have been declining over the last quarter century. Age at death, but not sex, was associated with the autopsy rate. These different results stress the importance of correct collection and analysis methods of data. [ABSTRACT FROM AUTHOR]

Purpose: Knee arthroscopies are regularly carried out in an outpatient setting. The purpose of this retrospective analysis was to investigate the impact of different local anaesthetics for spinal anaesthesia on operating room efficiency (perioperative process times) and postoperative recovery. This study aims to determine the optimal LA for SPA in patients undergoing knee arthroscopy at a day-surgery centre.Methods: Anaesthesia records of all patients undergoing knee arthroscopy under spinal anaesthesia from 2010 until 2017 were analysed. Patients were categorised as having received spinal anaesthesia with prilocaine, mepivacaine or chloroprocaine.Results: Three-hundred and nine patients were included. Postoperative recovery was significantly faster for chloroprocaine 1% compared with both other local anaesthetics regarding all stages of recovery until discharge. Perioperative processes and surgery time were significantly shorter when chloroprocaine was used. Early postoperative pain occurred more frequently and earlier after spinal anaesthesia with chloroprocaine. Nevertheless, pain intensity did not differ between groups.Conclusion: Spinal anaesthesia provides reliable blocks for outpatient knee arthroscopy. Considerations on the choice of local anaesthetic for spinal anaesthesia must include not only the recovery profile, but also the impact on operating room efficiency. Due to a superior recovery profile, low incidences of adverse side effects and raised operating room efficiency, chloroprocaine is the recommendable local anaesthetic for spinal anaesthesia in patients undergoing knee arthroscopy in an ambulatory setting. Since the frequency of SPA in patients undergoing outpatient knee arthroscopy is rising yearly, the results of this study are of high clinical relevance. The use of chloroprocaine leads to improved recovery, optimized perioperative processes and consecutively to a raised OR efficiency.Level Of Evidence: III. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the MRI macroscopic and microscopic parameters of mesorectal vasculature in rectal cancer patients.Methods: Thirteen patients with rectal adenocarcinoma underwent a dynamic contrast-enhanced MRI at 1.5 T using a blood pool agent at the primary staging. Mesorectal macrovascular features, i.e., the number of vascular branches, average diameter and length, were assessed from baseline-subtracted post-contrast images by two independent readers. Mesorectal microvascular function was investigated by means of area under the enhancement-time curve (AUC). Histopathology served as reference standard of the tumour response to CRT.Results: The average vessel branching in the mesorectum around the tumour and normal rectal wall was 8.2 ± 3.8 and 1.7 ± 1.3, respectively (reader1: p = 0.001, reader2: p = 0.002). Similarly, the tumour-surrounding mesorectum displayed circa tenfold elevated AUC (p = 0.01). Interestingly, patients with primary node involvement had a twofold higher number of macrovascular branches compared to those with healthy nodes (reader1: p = 0.005 and reader2: p = 0.03). A similar difference was observed between good and poor responders to CRT, whose tumour-surrounding mesorectum displayed 10.7 ± 3.4 and 5.6 ± 1.5 vessels, respectively (reader1/reader2: p = 0.02).Conclusions: We showed at baseline MRI of rectal tumours a significantly enhanced macrovascular structure and microvascular function in rectal tumour-surrounding mesorectum, and the association of primary mesorectal macrovascular parameters with node involvement and therapy response.Key Points: • Vascular MRI reveals macrovascular and microvascular abnormalities in the rectal tumour-surrounding mesorectum. • Formation of highly vascular stroma precedes the actual tumour invasion. • High macrovascular parameters are associated with node involvement. • Mesorectal vascular network differs for good and poor responders. [ABSTRACT FROM AUTHOR]

We investigate the blow-up of a weighted projective plane at a general point. We provide criteria and algorithms for testing if the result is a Mori dream surface and we compute the Cox ring in several cases. Moreover applications to the study of M¯0,n are discussed. [ABSTRACT FROM AUTHOR]

Merkel cell carcinoma (MCC) is a highly aggressive, often lethal neuroendocrine cancer. Its carcinogenesis may be either caused by the clonal integration of the Merkel cell polyomavirus into the host genome or by UV-induced mutations. Notably, virally-encoded oncoproteins and UV-induced mutations affect comparable signaling pathways such as RB restriction of cell cycle progression or p53 inactivation. Despite its low incidence, MCC recently received much attention based on its exquisite immunogenicity and the resulting major success of immune modulating therapies. Here, we summarize current knowledge on epidemiology, biology and therapy of MCC as conclusion of the project ‘Immune Modulating strategies for treatment of Merkel Cell Carcinoma’, which was funded over a 5-year period by the European Commission to investigate innovative immunotherapies for MCC. [ABSTRACT FROM AUTHOR]

In ecotoxicology, transcriptomics is an effective way to detect gene expression changes in response to environmental pollutants. Such changes can be used to identify contaminants or contaminant classes and can be applied as early warning signals for pollution. To do so, it is important to distinguish contaminant-specific transcriptomic changes from genetic alterations due to general stress. Here we present a first step in the identification of contaminant class-specific transcriptome signatures. Embryos of zebrafish (Danio rerio) were exposed to three substances (methylmercury, chlorpyrifos and Aroclor 1254, each from 24 to 48 hpf exposed) representing sediment typical contaminant classes. We analyzed the altered transcriptome to detect discriminative genes significantly regulated in reaction to the three applied contaminants. By comparison of the results of the three contaminants, we identified transcriptome signatures and biologically important pathways (using Cytoscape/ClueGO software) that react significantly to the contaminant classes. This approach increases the chance of finding genes that play an important role in contaminant class-specific pathways rather than more general processes. [ABSTRACT FROM AUTHOR]

Purpose: Using large-core biopsy needles in CT-guided percutaneous transthoracic needle biopsies (PTNB) may be advantageous in terms of larger specimens, which facilitate more extensive histopathological, immunohistochemical, and molecular examination of tumor tissue. The aim of this study was to evaluate the success rate and safety in CT-guided PTNB using 10G large-core biopsy needles.Methods and Materials: 35 patients with intrathoracic lesions suspected of malignancy underwent CT-guided PTNB using dedicated large-core biopsy needles (10G Spirotome™, Medinvents, Hasselt, Belgium). Location, tumor size, number of pleural passes, number of biopsies, histologic result, and complications (pneumothorax, bleeding) were recorded.Results: Lesion location varied from pleural to hilar location. Mean tumor size was 3.5 cm (range 0.7-9.2 cm). Only one pleural passage was necessary in all patients. Mean distance from the pleura to the lesion was 2.6 cm (max 9.2 cm). Large-core biopsy (10G) was successful in 88.6%. Pneumothorax was found in 40%. Minor intraparenchymal bleeding was present in 14 patients. No major complications were recorded.Conclusion: Large-core biopsy with 10G did not show higher complication rates compared to literature. It is technically feasible and safe. The obtained larger specimens may especially be helpful for the increasing demands of extensive molecular analysis for stratified patient care. [ABSTRACT FROM AUTHOR]

Background: Low anterior resection (LAR) for rectal cancer is a potentially challenging operation due to limited space in the pelvis. CT pelvimetry allows to quantify pelvic space, so that its relationship with outcome after LAR may be assessed. Studies investigating this, however, yielded conflicting results. We hypothesized that a small pelvis is associated with a higher rate of incomplete mesorectal excision, anastomotic leakages, and increased rate of urinary dysfunction in patients operated for rectal cancer. Methods: In a single-center retrospective analysis, we studied 74 patients that underwent LAR for rectal cancer with primary anastomosis. Thin-layered multi-slice CT datasets were used for slice by slice depiction of the inner pelvic surface, and the inner pelvic volume was automatically compounded. The primary outcome was quality of total mesorectal excision (TME; Mercury grading); secondary outcomes were anastomotic leakage and urinary dysfunction with regard to pelvic dimensions. Univariate analyses and multiple logistic regression analyses were performed for the primary and the secondary outcomes. Results: Shorter obstetric conjugate diameters were associated with a higher probability of a worse TME quality (110.8 ± 10.2 vs. 105.0 ± 8.6 mm; OR 0.85; 95% CI 0.73-0.99; p = 0.038). Short interspinous distance showed a trend towards an increased risk for deteriorated TME quality (OR 0.88; 95% CI 0.76-1.0; p = 0.06). Anastomotic leakage was associated with anemia (OR 2.77; 95% CI 1.0-7.7; p = 0.047). Association between pelvic diameters or pelvic volume and anastomotic leakage or urinary dysfunction was not observed. Perioperative blood transfusions were administered more often in patients with postoperative urinary dysfunction (OR 17.67; 95% CI 2.44-127.7; p = 0.004). Conclusion: Shorter obstetric conjugate diameter might be a risk factor for incompleteness of total mesorectal excision. Anastomotic leakage seems to be influenced more by clinical factors such as anemia rather than pelvic dimensions. Further studies have to prove the influence of pelvic diameter on local recurrence of rectal cancer after LAR. [ABSTRACT FROM AUTHOR]

Copyright of Der Hautarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Approximately 10% of gastric carcinomas (GC) worldwide are associated with Epstein-Barr virus (EBV). GC is one of the most frequent human malignancies associated with EBV. The latent expression of the EBV-oncogene BARF1 is restricted to epithelial malignancies. To investigate the underlying BARF1-related mechanisms of oncogenic epithelial transformation, we analyzed gene expression profiles of a BARF1-transfected epithelial (HaCaT+) and the corresponding BARF1-negative (HaCaT-) cell line by cDNA microarray analysis. Real-time PCR was performed to confirm the cDNA microarray results. In addition, immunohistochemistry and fluorescence in situ hybridization were performed on a tissue microarray of 181 GC including 11 EBV-associated GC. Among other genes cyclin D1 expression was significantly upregulated in HaCaT+ on the transcriptional and protein level. Cyclin D1 protein expression in GC revealed a significant overexpression of cyclin D1 in EBV-associated GC (p<0.012) but not in EBV-negative GC. Cyclin D1 FISH showed that cyclin D1 overexpression was not due to gene amplification in EBV-associated GC. Cyclin D1 is induced in HaCaT+ by BARF1 and is overexpressed in EBV-associated GC indicating an interaction of viral BARF1 and cyclin D1. [ABSTRACT FROM AUTHOR]

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Background: Surgical staplers currently all rely on the same staple form-the "B" which necessitates a high delivery profile (12 mm). A novel "D" shape staple allows for an extremely low profile of the applicator. The acute and long-term efficacy of a D-shaped staple (Cardica, Redwood City, CA, USA) was compared to conventional B-form staples (Covidien, Norwalk, CN, USA) in an animal model for intestinal transections and anastomoses.Methods: Jejunojejunal anastomoses (JJ) were performed via mini-laparotomy in a swine model. White & blue D- and B-shaped staples were studied in three groups (planned survival 14-84 days). Intraoperative assessment included completeness of staple line, hemostasis, and need for intervention. Postoperatively, animals were evaluated for complications. At the time of sacrifice, gross pathological and histological assessments were performed.Results: Twenty-three animals had 40 anastomoses (23 "D" and 17 "B" staple anastomoses) with no intraoperative mortalities. One "D" staple application required a manual extension of the cut. Acute hemostasis was 100%. Group 1 (n = 5) compared white staples in JJs (D staple n = 5; B staple n = 5; 14-day survival = 100%). Group 2 (n = 12) compared white staples in JJs (D staple n = 12; B staple n = 6; 34-day survival = 92 %). One animal died on day 4 for a non-staple related cause. Group 3 (n = 6) compared blue staples in JJs (D staple n = 6; B staple n = 6; 84 day survival = 84%). One animal died on day 18 due to an obstruction at the B staple JJ caused by stricture. There were no other bleeding, leaks or strictures in any of the groups. Gross pathology and histology were unremarkable in all JJs.Conclusions: This study showed no difference in intraoperative performance and the chronic healing response in JJs between D- and B-shaped staples. Based on these findings, the D-shaped staple elicits a normal healing response in jejunostomies and offers the possibility of clinical use of this advance in staple design. [ABSTRACT FROM AUTHOR]

Transcriptomics is often used to investigate changes in an organism's genetic response to environmental contamination. Data noise can mask the effects of contaminants making it difficult to detect responding genes. Because the number of genes which are found differentially expressed in transcriptome data is often very large, algorithms are needed to reduce the number down to a few robust discriminative genes. We present an algorithm for aggregated analysis of transcriptome data which uses multiple fold-change thresholds (threshold screening) and p values from Bayesian generalized linear model in order to assess the robustness of a gene as a potential indicator for the treatments tested. The algorithm provides a robustness indicator (ROBI) as well as a significance profile, which can be used to assess the statistical significance of a given gene for different fold-change thresholds. Using ROBI, eight discriminative genes were identified from an exemplary dataset ( Danio rerio FET treated with chlorpyrifos, methylmercury, and PCB) which could be potential indicators for a given substance. Significance profiles uncovered genetic effects and revealed appropriate fold-change thresholds for single genes or gene clusters. Fold-change threshold screening is a powerful tool for dimensionality reduction and feature selection in transcriptome data, as it effectively reduces the number of detected genes suitable for environmental monitoring. In addition, it is able to unmask patterns in altered genetic expression hidden by data noise and reduces the chance of type II errors, e.g., in environmental screening. [ABSTRACT FROM AUTHOR]

Purpose: Dynamic implants for the human spine are used to re-establish regular segmental motion. However, the results have often been unsatisfactory and complications such as screw loosening are common. Individualisation of appliances and precision implantation are needed to improve the outcome of this procedure. Computer simulation, virtual implant optimisation and image guidance were used to improve the technique. Methods: A human lumbar spine computer model was developed using multi-body simulation software. The model simulates spinal motion under load and degenerative changes. After virtual degeneration of a L4/5 segment, virtual pedicle screw-based implants were introduced. The implants' positions and properties were iteratively optimised. The resulting implant positions were used as operative plan for image guidance and finally implemented in a physical spine model. Results: In the simulation, the introduction and optimisation of virtually designed dynamic implants could partly compensate for the effects of virtual lumbar segment degeneration. The optimised operative plan was exported to two different image-guidance systems for transfer to a physical spine model. Conclusion: Three-dimensional computer graphic simulation is a feasible means to develop operative plans for dynamic spinal stabilization. These operative plans can be transferred to commercially available image-guidance systems for use in implantation of physical implants in a spine model. This concept has important potential in the design of operative plans and implants for individualised dynamic spine stabilization surgery. [ABSTRACT FROM AUTHOR]

Background:The metastasis suppressor 1 (MTSS1) is a newly discovered protein putatively involved in tumour progression and metastasis.Material and Methods:Immunohistochemical expression of MTSS1 was analysed in 264 non-small-cell lung carcinomas (NSCLCs).Results:The metastasis suppressor 1 was significantly overexpressed in NSCLC compared with normal lung (P=0.01). Within NSCLC, MTSS1 expression was inversely correlated with pT-stage (P=0.019) and histological grading (P<0.001). NSCLC with MTSS1 downregulation (<20%) showed a significantly worse outcome (P=0.007). This proved to be an independent prognostic factor in squamous cell carcinomas (SCCs; P=0.041), especially in early cancer stages (P=0.006).Conclusion:The metastasis suppressor 1 downregulation could thus serve as a stratifying marker for adjuvant therapy in early-stage SCC of the lung. [ABSTRACT FROM AUTHOR]