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BackgroundWhite matter hyperintensities (WMH), a biomarker of small vessel disease, are often found in Alzheimer’s disease (AD) and their advanced detection and quantification can be beneficial for research and clinical applications. To investigate WMH in large-scale multicenter studies on cognitive impairment and AD, appropriate automated WMH segmentation algorithms are required. This study aimed to compare the performance of segmentation tools and provide information on their application in multicenter research.MethodsWe used a pseudo-randomly selected dataset (n = 50) from the DZNE-multicenter observational Longitudinal Cognitive Impairment and Dementia Study (DELCODE) that included 3D fluid-attenuated inversion recovery (FLAIR) images from participants across the cognitive continuum. Performances of top-rated algorithms for automated WMH segmentation [Brain Intensity Abnormality Classification Algorithm (BIANCA), lesion segmentation toolbox (LST), lesion growth algorithm (LGA), LST lesion prediction algorithm (LPA), pgs, and sysu_media] were compared to manual reference segmentation (RS).ResultsAcross tools, segmentation performance was moderate for global WMH volume and number of detected lesions. After retraining on a DELCODE subset, the deep learning algorithm sysu_media showed the highest performances with an average Dice’s coefficient of 0.702 (±0.109 SD) for volume and a mean F1-score of 0.642 (±0.109 SD) for the number of lesions. The intra-class correlation was excellent for all algorithms (>0.9) but BIANCA (0.835). Performance improved with high WMH burden and varied across brain regions.ConclusionTo conclude, the deep learning algorithm, when retrained, performed well in the multicenter context. Nevertheless, the performance was close to traditional methods. We provide methodological recommendations for future studies using automated WMH segmentation to quantify and assess WMH along the continuum of cognitive impairment and AD dementia.

Lukas Rath, Friedrich Jokisch, Gerald Bastian Schulz, Alexander Kretschmer, Alexander Buchner, Christian G Stief, Philipp Weinhold Department of Urology, Ludwig-Maximilians-University, Munich, GermanyCorrespondence: Philipp WeinholdDepartment of Urology, Ludwig-Maximilians-University, Marchioninistrasse 15, Munich, 81377, GermanyTel +4989-4400-73528Fax +49894400-78735Email philipp.weinhold@med.uni-muenchen.dePurpose: There are only a few case reports and case series that investigated combined laparoscopic or robotic surgery for simultaneous prostate and kidney cancer. In this study, we want to close a gap in existing research to assess the feasibility and oncological outcome of combined open prostatectomy and kidney surgery.Methods: We retrospectively analyzed patients who underwent a combined open prostatectomy and either a partial or complete nephrectomy from 2013 to 2020. Descriptive statistics were used to assess perioperative parameters and the 12-month functional and oncological outcomes after combined surgery.Results: We identified 10 patients undergoing combined open surgery. Partial nephrectomy was performed in 4, radical nephrectomy in 6 patients. For prostate cancer, histopathological analysis showed a tumor stage ≥ pT2c in all 10 patients. For renal tumors, histopathological analysis showed clear cell renal cell carcinoma in 8 patients and oncocytoma in 2 patients. Operating time was 177 ± 36 minutes. Two perioperative complications (Clavien 2a and 3) were observed. Three months postoperatively, the International Index of Erectile Function (IIEF-5) score was 5.6 ± 5.9, the ICIQ-SF score was 7.3 ± 5.6 and were using 1.9 ± 2.2 pads per day. This improved after 12 months postoperatively, as patients had an IIEF-5 score of 6.33 ± 6.5, an ICIQ-SF score of 4.4 ± 5.7 and were using pads 0.9 ± 1.7 per day.Conclusion: In this study, we showed that open surgery is a safe and valid approach for combined prostatectomy and renal surgery with acceptable complications and oncological outcomes. The combined open approach could be a good alternative to combined laparoscopic/robotic surgery in this field, especially to treat patients with advanced renal tumors or previous abdominal surgery or radiation.Keywords: retropubic prostatectomy, kidney surgery, simultaneous prostate and kidney cancer, combined surgery

The scale-sensitive fractal analysis (SSFA) of dental microwear textures is traditionally performed using the software Toothfrax. SSFA has been recently integrated to the software MountainsMap® as an optional module. Meanwhile, Toothfrax support has ended. Before switching to the new module, the outputs between the two software packages must be compared for consistency. We have performed such a test using Bayesian modelling on three datasets including dental surfaces of sheep (Merceron, Ramdarshan, et al., 2016) and guinea pigs (Winkler, Schulz-Kornas, Kaiser, Cuyper, et al., 2019) from controlled feeding experiments, as well as surfaces of quartzite and flint flakes used in an actualistic archeological experiment on cleaning procedures (Pedergnana, Calandra, Bob, et al., 2020). We found that the two software packages calculate significantly different values for the SSFA parameters epLsar, Asfc, HAsfc9 and R2, even when the same settings are used. Nevertheless, the treatments (different diets or cleaning procedures) are discriminated similarly within each dataset. While the new software module is as good as the original software to differentiate treatments, our results imply that the outputs from the two software packages are not directly comparable and, as such, cannot be merged. Surface texture analysts should therefore consider re-analyzing published surfaces before integrating them in their studies.

Aim: The aim is to record existing attitudes, influencing factors and specialised requirements with regard to the training of medical students in specialist outpatient care with doctors working in outpatient care.Method: Between September 2020 and May 2021, individual interviews with 15 specialists employed in outpatient care were held as part of this qualitative study. The recorded interviews were evaluated structurally in accordance with the Kuchartz method.Results: Enhanced outpatient training for medical students in specialist teaching practices was considered as important by all participants. Among other things, motivational factors were pleasure in teaching, a feeling of duty, the desire to pass something on, the need to convey one’s own ideas and to generate future talent for the field. A lack of time, greater organisational effort and legal concerns were stated as hurdles. Reducing organisational effort for teaching practices, appreciation of their teaching activity and financial considerations were in particular given as significant incentives for participating. The attitude of participants towards financial remuneration was heterogeneous. Different specialist features and requirements for student training were mapped out. Conclusion: This study provides, for the first time, findings about teaching in specialist outpatient establishments. They point to a great degree of willingness of specialist doctors to undertake teaching and provide starting points for creating concepts about producing teaching practices in specialist fields. Further quantitative investigation is required to substantiate the findings before us.

The sharp decline in seminatural areas worldwide is undisputed, but the consequences of this decline, apart from the loss of biodiversity, cannot be fully assessed. To restore ecosystems or landscapes, it is essential to have so-called reference sites. We want to show how reliable reference sites can be found in heavily used landscapes with the help of independent sources, and we present an approach that can be used in other regions, because it is very well suited for developing essential databases in the context of theses at different levels. A forest of seminatural stocking was selected in northeast Germany as a case study. The mapping of archival sources and the analyses of historical maps as well as field investigations were combined to reconstruct the dynamics of vegetation and soil for the last several centuries to thousands of years. Palynological data from nearby sites show that the study area has been forested for several millennia and has been less influenced by humans in the last 450 years. Together with historical maps of tree species composition, it allows to infer that the specific forest has been preserved in good ecological conditions for at least 250 years. Soil inventory and field studies on two catenas and corings support this conclusion, as they rarely show signs of anthropogenic erosion and related colluviation. Using a multisource approach, it is possible to identify potential reference sites that provide a reliable basis for ecosystem or landscape restoration.

Anastasia Murtha-Lemekhova,1,2 Juri Fuchs,1,2 Erik Schulz,1,2 Anthe Suzan Sterkenburg,1 Philipp Mayer,2,3 Jan Pfeiffenberger,2,4 Katrin Hoffmann1,2 1Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany; 2RELIVE Initiative, Heidelberg University Hospital, Heidelberg, Germany; 3Department of Diagnostic and Interventional Radiology, Heidelberg University Hospital, Heidelberg, Germany; 4Department of Gastroenterology and Hepatology, Heidelberg University Hospital, Heidelberg, GermanyCorrespondence: Katrin HoffmannDepartment of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Im Neuenheimer Feld 420, Heidelberg, 69120, GermanyTel +49 6221 56 6110Fax +49 6221 56 5450Email katrin.hoffmann@med.uni-heidelberg.deBackground: Aberrant subtypes of hepatocellular carcinoma (HCC) account for 20– 30% of all HCCs and habitually present a challenge in diagnosis and treatment. Scirrhous hepatocellular carcinoma (s-HCC) is often misdiagnosed as cholangiocarcinoma, fibrolamellar hepatocellular carcinoma, or metastasis.Methods: Electronic databases (PubMed, Web of Knowledge, Google Scholar, Cochrane Library, and WHO International Clinical Trials Registry Platform) were searched for publications on scirrhous hepatocellular carcinoma without date or language restrictions. Quality assessment was performed using a tool proposed by Murad et al for case reports and series. For observational studies, MINORS quality assessment tool was used. This study was registered at PROSPERO (CRD42020212323).Results: S-HCC arises in patients with chronic hepatitis (hepatitis B in 60% and hepatitis C in 21%). S-HCC primarily affects men with a mean age of 55.8 years. Serum AFP is elevated above 20IU/mL in 66.7% of the patients. On ultrasound, s-HCC presents as hypoechoic or mosaic pattern lesions (47.6% each) and causes a retraction of the liver surface (70%) when near the capsule. Delayed enhancement of the tumor is evident in 87.0%. On MRI, 65.0% of s-HCCs show a target appearance. Histopathologic pattern is mostly irregular (97.6%). Lesions show a bulging appearance (100%), septae (85.6%) and a central scar (63.5%), and usually lack central necrosis (75%). Immunohistochemistry shows HepPar 1 positivity in 64.6%, CK7 in 40.7%, and EMA in 41.9%. The 5-year overall survival rate estimates 45.2% and 45.5% of the patients experience a recurrence after hepatectomy.Conclusion: S-HCC is a rare subtype of HCC primarily arising in hepatitis- or cirrhosis-afflicted livers and incorporates atypical radiological and histopathological HCC features. Despite lower recurrence rates, overall survival of patients with s-HCC is poorer than generally for HCC, underlining the need for individualized treatment. Patients with atypical lesions of the liver should be referred to tertiary hospitals for interdisciplinary assessment and treatment.Keywords: scirrhous HCC, s-HCC, rare liver tumors, RELIVE initiative

Introduction: Clinical trials currently evaluate the use of mesenchymal stem cells (MSCs) for the treatment of non-union bone fractures. The stem cells are injected directly into the non-union area of a bone via a cannula. During this injection process, pressure and shear forces affect the MSCs which could influence the viability of the cells. One parameter that influences the level of the shear forces is the volume flow. The aim of this study is to show whether the injection process with two different volume flows influences the cell viability. Methods: MSCs were isolated from bone tissue, harvested during arthroplasty. Afterwards, they were diluted to a concentration of 1 million cells/mL and 1 mL of this suspension was injected through a cannula with 200 mm length and 2 mm diameter (14 G) with volume flows of 38 and 100 mL/min. The evaluation was performed by detecting living, apoptotic, and dead cells using flow cytometry. The statistical analysis was performed with a Kruskal-Wallis-test to identify significant differences and with a TOST procedure for significant equivalence. The significance level was set to 5 % and the equivalence margin to 20 %. Results: The cell population of healthy cells was in the control group 85.88±2.98 %. After an injection with 38 mL/min the population of healthy cells was 86.04±2.53 % and with 100 ml/min 85.48±1.64 %. The statistical analysis revealed no significant difference between these groups (p = 0.99), but a significant equivalence between the control group and the two volume flows (38 mL/min: p = 0.002, 100 mL/min: p = 0.001). In addition the results show no increase of apoptotic and dead cells in the population after injection. Conclusion: The results indicate that the injection process through the cannula with these volume flows has no effect on the viability of the MSCs.

Myriam Koch,1 Laura Gräfenstein,2,3 Julia Karnosky,4 Christian Schulz,1 Michael Koller2 1Department of Internal Medicine 2, University Hospital Regensburg, Regensburg, Germany; 2Center for Clinical Studies University Hospital Regensburg, Regensburg, Germany; 3Hospital Wörth an der Donau, Germany; 4Department of Surgery, University Hospital Regensburg, Regensburg, GermanyCorrespondence: Myriam KochKlinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg, Franz-Josef-Strauß Allee 11, Regensburg, D-93053, GermanyTel +49 941 9440Email Myriam.Koch@ukr.deBackground: Overall survival is the ultimate criterion for the therapy of lung cancer, but psychosocial care, which helps the patient to cope with the disease, becomes a more and more important issue in the treatment of this life-threatening disease.Methods: We report the satellite project within a prospective, international, cross-cultural, multicenter study to validate the EORTC QLQ-LC29, a new designed module to assess the quality of life of lung cancer patients. The participants filled in the EORTC QLQ-C30, the recently updated lung cancer module QLQ-LC29 and the Hornheide questionnaire (HSI).Results: A total of 81 patients (32 female and 49 male, mean age 65.2 years, SD = 9.7) were enrolled in this study by completing the questionnaires. Fatigue (mean 55.4, SD = 26.3) and dyspnea (mean 46.3, SD = 36.2) were the most prominent symptoms. Thirty-nine patients (48.1%) according to the HSI needed psychosocial support. When using the EORTC questionnaires as screening instrument with 50 as cut-off in contrast only 29.5% of our patients needed psychosocial support. The need for psychosocial support according to the HSI correlated most with the EORTC scales “fatigue” (38.3% overlap between the two questionnaires), “existential fear” (38.3% overlap between the two questionnaires) and worse “global quality of life” (27.2% overlap between the two questionnaires).Conclusion: If psychosocial distress is at the core, the HSI is a suitable instrument for quick screening. The EORTC measures help to specify impaired quality of life areas and also cover somatic symptoms that are specific for cancer patients. Once psychosocial distress has been ascertained, clinicians should be particularly aware of specific problems regarding “fatigue”, “existential fear” and diminished “global quality of life”.Trial Registration: clinicaltrials.gov, reference number NCT02745691. Registered 20 April 2016.Keywords: lung cancer, quality of life, psychosocial burden, EORTC QLQ-C30/QLQ-LC29 questionnaire, Hornheide screening instrument

In endovascular aneurysm repair (EVAR) procedures, the stent graft navigation and implantation is currently performed under a two-dimensional (2D) imaging based guidance requiring X-rays and contrast agent. In this work, a novel 3D stent graft guidance approach based on tracking systems is introduced. A calibration method and the visualization of the stent graft guidance are described. The tracking based stent graft guidance is evaluated by conducting an EVAR procedure on a torso phantom using a stent graft system equipped with an optical fiber and three EM sensors. The physicians were able to navigate the stent graft to the landing zone, and to place and implant it as intended using the introduced guidance. This showed that the application of the stent graft guidance is feasible in a clinical environment and promising for the reduction of radiation and contrast agent.

Recovery procedures are targeted at correcting issues encountered by robots. What are people’s opinions of a robot during these recovery procedures? During an experiment that examined how a mobile robot moved, the robot would unexpectedly pause or rotate itself to recover from a navigation problem. The serendipity of the recovery procedure and people’s understanding of it became a case study to examine how future study designs could consider breakdowns better and look at suggestions for better robot behaviors in such situations. We present the original experiment with the recovery procedure. We then examine the responses from the participants in this experiment qualitatively to see how they interpreted the breakdown situation when it occurred. Responses could be grouped into themes of sentience, competence, and the robot’s forms. The themes indicate that the robot’s movement communicated different information to different participants. This leads us to introduce the concept of movement acts to help examine the explicit and implicit parts of communication in movement. Given that we developed the concept looking at an unexpected breakdown, we suggest that researchers should plan for the possibility of breakdowns in experiments and examine and report people’s experience around a robot breakdown to further explore unintended robot communication.

Objectives: By now, many long-term symptoms after COVID-19 are described, mostly concerning hospitalized patients. Our aim was to investigate the long-term effect of COVID-19 on the lung function with focus on the diffusion capacity of athletes. Methods: 99 athletes (34.1711.94 years, 56% female) after COVID-19 and 36 athletes (25.806.70 years, 65% female) without COVID-19 as controls were included. Symptom severity and lung function were assessed. Lung function of controls were compared with athletes after COVID-19 and changes in patients with dyspnea (during infection and at time of appointment) and changes over time between infection and examination on lung function were examined. Results: Exertional dyspnea during the infection was reported by 51% of athletes after COVID-19, respectively 27% at the time of examination (158137 days after infection). 30% of athletes after COVID-19 showed a reduced Diffusion Capacity of the Lungs for Carbon Monoxide (DLCO

Genetic introgression of farmed salmon into wild populations can damage the genetic integrity of wild stocks and is therefore considered as an environmental threat. One possible solution is to induce sterility in farmed salmon. We have searched for proteins potentially essential for germline survival in Atlantic salmon. One of these is the argonaute protein Piwil1, known to be required for germ cell survival. To examine Piwil1 function in salmon, we induced indels in the N domain by CRISPR-Cas9. The encoded domain is present in all vertebrate Piwi proteins and has been linked to Tdrd1 protein interaction and PAZ lobe structure. The F0 founder generation of piwil1 crispant males and females displayed a mosaic pattern of piwil1 mutations, exhibiting highly mutated alleles (53%–97%) in their fin gDNA samples. In general, piwil1 crispants carried germ cells, went through puberty and became fertile, although a transient and partial germ cell loss and delays during the spermatogenic process were observed in many male crispants, suggesting that Piwil1 functions during salmon spermatogenesis. By crossing highly mutated F0 founders, we produced F1 fish with a mixture of: loss-of-function alleles (−); functional in frame mutated alleles (+) and wt alleles (+). In F1, all piwil1−/− fish lacked germ cells, while piwil1+/+ siblings showed normal ovaries and testes. Yet, most juvenile F1 piwil1+/−males and females displayed an intermediate phenotype with a higher somatic/germ cell ratio without an increase in germ cell apoptosis, suggestive of a gene dose effect on the number of germ cells and/or insufficient replacement of lost germ cells in heterozygous fish. Interestingly, the two longest in-frame indels in the N domain also ensured germ cell loss. Hence, the loss of 4–6 aa in this region Phe130-Ser136 may result in crucial changes of the protein structure, potentially affecting piRNA binding of the PAZ lobe, and/or affecting the binding of Piwil1 interacting proteins such as Tdrd protein, with critical consequences for the survival of primordial germ cells. In conclusion, we show that loss of piwil1 leads to loss of germ cells in salmon and that part of the N domain of Piwil1 is crucial for its function.

This paper focuses on a particular form of stock-market trades around ex-dividend days, so-called “cum-ex” transactions, which have resulted in major revenue losses due to illegitimate tax refunds in Germany and other European nations. Until 2012, the loophole in the German withholding tax scheme made it possible for cum-ex traders to receive withholding-tax certificates without prior withholding-tax payment. Because a certain category of investors might use the tax certificates to gain a tax exemption, this opened up the prospect of a particular form of tax arbitration. It was not until 2018 that a cross-border investigation team called the Cum-Ex Files revealed the scandal to its full extend. This paper will mainly focus on the cum-ex scandal in Germany since the literature on the topic is very limited.