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Regarding the prevention of injuries and rehabilitation of the human hand, musculoskeletal simulations using an inverse dynamics approach allow for insights of the muscle recruitment and thus acting forces on the hand. Currently, several hand models from various research groups are in use, which are mainly validated by the comparison of numerical and anatomical moment arms. In contrast to this validation and model-building technique by cadaver studies, the aim of this study is to further validate a recently published hand model [1] by analyzing numerically calculated muscle activities in comparison to experimentally measured electromyographical signals of the muscles. Therefore, the electromyographical signals of 10 hand muscles of five test subjects performing seven different hand movements were measured. The kinematics of these tasks were used as input for the hand model, and the numerical muscle activities were computed. To analyze the relationship between simulated and measured activities, the time difference of the muscle on- and off-set points was calculated, which resulted in a mean on- and off-set time difference of 0.58 s between the experimental data and the model. The largest differences were detected for movements that mainly addressed the wrist. One major issue comparing simulated and measured muscle activities of the hand is cross-talk. Nevertheless, the results show that the hand model fits the experiment quite accurately despite some limitations and is a further step toward patient-specific modeling of the upper extremity.

\(\bf Purpose\) Controlled ovarian stimulation significantly amplifies the number of maturing and ovulated follicles as well as ovarian steroid production. The ovarian hyperstimulation syndrome (OHSS) increases capillary permeability and fluid extravasation. Vascular integrity intensely is regulated by an endothelial glycocalyx (EGX) and we have shown that ovulatory cycles are associated with shedding of EGX components. This study investigates if controlled ovarian stimulation impacts on the integrity of the endothelial glycocalyx as this might explain key pathomechanisms of the OHSS. \(\bf Methods\) Serum levels of endothelial glycocalyx components of infertility patients (n=18) undergoing controlled ovarian stimulation were compared to a control group of healthy women with regular ovulatory cycles (n=17). \(\bf Results\) Patients during luteal phases of controlled ovarian stimulation cycles as compared to normal ovulatory cycles showed significantly increased Syndecan-1 serum concentrations (12.6 ng/ml \(6.11^{25th}\)–\(19.13^{75th}\) to 13.9 ng/ml \(9.6^{25th}\)–\(28.9^{75th}\); p=0.026), indicating shedding and degradation of the EGX. \(\bf Conclusion\) A shedding of EGX components during ovarian stimulation has not yet been described. Our study suggests that ovarian stimulation may affect the integrity of the endothelial surface layer and increasing vascular permeability. This could explain key features of the OHSS and provide new ways of prevention of this serious condition of assisted reproduction.

Coronavirus disease 2019 (COVID-19) spawned a global health crisis in late 2019 and is caused by the novel coronavirus SARS-CoV-2. SARS-CoV-2 infection can lead to elevated markers of endothelial dysfunction associated with higher risk of mortality. It is unclear whether endothelial dysfunction is caused by direct infection of endothelial cells or is mainly secondary to inflammation. Here, we investigate whether different types of endothelial cells are susceptible to SARS-CoV-2. Human endothelial cells from different vascular beds including umbilical vein endothelial cells, coronary artery endothelial cells (HCAEC), cardiac and lung microvascular endothelial cells, or pulmonary arterial cells were inoculated in vitro with SARS-CoV-2. Viral spike protein was only detected in HCAECs after SARS-CoV-2 infection but not in the other endothelial cells tested. Consistently, only HCAEC expressed the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2), required for virus infection. Infection with the SARS-CoV-2 variants B.1.1.7, B.1.351, and P.2 resulted in significantly higher levels of viral spike protein. Despite this, no intracellular double-stranded viral RNA was detected and the supernatant did not contain infectious virus. Analysis of the cellular distribution of the spike protein revealed that it co-localized with endosomal calnexin. SARS-CoV-2 infection did induce the ER stress gene EDEM1, which is responsible for clearance of misfolded proteins from the ER. Whereas the wild type of SARS-CoV-2 did not induce cytotoxic or pro-inflammatory effects, the variant B.1.1.7 reduced the HCAEC cell number. Of the different tested endothelial cells, HCAECs showed highest viral uptake but did not promote virus replication. Effects on cell number were only observed after infection with the variant B.1.1.7, suggesting that endothelial protection may be particularly important in patients infected with this variant. Supplementary Information The online version contains supplementary material available at 10.1007/s00395-021-00882-8.

Coronavirus disease 2019 (COVID-19) spawned a global health crisis in late 2019 and is caused by the novel coronavirus SARS-CoV-2. SARS-CoV-2 infection can lead to elevated markers of endothelial dysfunction associated with higher risk of mortality. It is unclear whether endothelial dysfunction is caused by direct infection of endothelial cells or is mainly secondary to inflammation. Here, we investigate whether different types of endothelial cells are susceptible to SARS-CoV-2. Human endothelial cells from different vascular beds including umbilical vein endothelial cells, coronary artery endothelial cells (HCAEC), cardiac and lung microvascular endothelial cells, or pulmonary arterial cells were inoculated in vitro with SARS-CoV-2. Viral spike protein was only detected in HCAECs after SARS-CoV-2 infection but not in the other endothelial cells tested. Consistently, only HCAEC expressed the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2), required for virus infection. Infection with the SARS-CoV-2 variants B.1.1.7, B.1.351, and P.2 resulted in significantly higher levels of viral spike protein. Despite this, no intracellular double-stranded viral RNA was detected and the supernatant did not contain infectious virus. Analysis of the cellular distribution of the spike protein revealed that it co-localized with endosomal calnexin. SARS-CoV-2 infection did induce the ER stress gene EDEM1, which is responsible for clearance of misfolded proteins from the ER. Whereas the wild type of SARS-CoV-2 did not induce cytotoxic or pro-inflammatory effects, the variant B.1.1.7 reduced the HCAEC cell number. Of the different tested endothelial cells, HCAECs showed highest viral uptake but did not promote virus replication. Effects on cell number were only observed after infection with the variant B.1.1.7, suggesting that endothelial protection may be particularly important in patients infected with this variant.

Grenzen, Räume und Identitäten. Der Oberrhein und seine Nachbarregionen von der Antike bis zum Hochmittelalter, hg. von Sebastian Brather und Jürgen Dendorfer (Archäologie und Geschichte, Freiburger Forschungen zum ersten Jahrtausend in Südwestdeutschland, Bd. 22). Ostfildern: Jan Thorbecke Verlag 2017. 587 S., zahlr. Abb. ISBN 978-3-7995-7372-6. Geb. € 73,–

Jürgen Dendorfer / Heinz Krieg / R. Johanna Regnath (Hg.), Die Zähringer. Rang und Herrschaft um 1200 (Veröffentlichung des Alemannischen Instituts Freiburg i. Br., Bd. 85), Ostfildern: Jan Thorbecke 2018. XXIV, 518 S. ISBN 978-3-7995-1296-1. € 35,–

To report on 10 years of high-risk service screening with annual MRI in the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC). A cohort of 4,573 high-risk, previously unaffected women (954 BRCA1 carriers, 598 BRCA2 carriers, 3021 BRCA1/2 non-carriers) participating in the GC-HBOC surveillance program was prospectively followed. Screening outcomes for 14,142 screening rounds with MRI between 2006 and 2015 were analyzed and stratified by risk group, type of screening round, and age. A total of 221 primary breast cancers (185 invasive, 36 in situ) were diagnosed within 12 months of an annual screening round with MRI. Of all cancers, 84.5% (174/206, 15 unknown) were stage 0 or I. In BRCA1 carriers, 16.9% (10/59, 5 unknown) of all incident cancers (screen-detected and interval cancers combined) and in BRCA2 carriers 12.5% (3/24, 4 unknown) were stage IIA or higher, compared to only 4.8% (2/42, 2 unknown) in high-risk BRCA1/2 non-carriers. Program sensitivity was 89.6% (95% CI 84.9–93.0) with no significant differences in sensitivity between risk groups or by age. Specificity was significantly lower in the first screening round (84.6%, 95% CI 83.6–85.7) than in subsequent screening rounds (91.1%, 95% CI 90.6–91.7), p

Die Freiburger Stadtrechte des hohen Mittelalters (1120 – 1293). Edition, Übersetzung, Einordnung, hg. von Marita Blattmann, Jürgen Dendorfer, Mathias Kälble und Heinz Krieg, unter Mitarbeit von Benjamin Torn und Meret Wüthrich. Freiburg im Breisgau: Stadtarchiv 2020. 410 S. ISBN 978-3-923272-44-0. € 30,–

Introduction Back problems represent one of the leading causes of accouchers’ work-related musculoskeletal morbidities. The correct execution of birth-related maneuvers including manual perineal protection is crucial not only for the mother and child but also for obstetricians and midwives to reduce any strain on their musculoskeletal system. Therefore, the overall aim of this study was to test the feasibility of determining the effect of different accouchers’ postures (standing and kneeling) on their musculoskeletal system. Methods The biomechanical analysis is based on musculoskeletal simulations that included motion recordings of real deliveries as well as deliveries conducted on a birthing simulator. These simulations were then used to determine individual joints’ loads. Results In the kneeling posture, both a low intra-operator variability and a lower average maximum load of the lower back was observed. For the standing position the spine load was reduced by pivoting the elbow on the accouchers’ thigh, which in turn was associated with a significantly greater load on the shoulder joint. Conclusion The study demonstrated the feasibility of our technique to assess joints loads. It also provided initial data indicating that a posture that reduces spinal flexion and tilt, achieved in this study by the kneeling, can significantly reduce the strain on the practitioner’s musculoskeletal system.

Vorträge und Forschungen, Bd. 85 (2018): Vorträge und Forschungen: Die römische Kurie und das Geld. Von der Mitte des 12. Jahrhunderts bis zum frühen 14. Jahrhundert

Additional file 2: Figure S1. ROC curves for detecting pCR by MRI and US among patients with both imaging assessments. Data are shown for all tumors (A) and for patients with HR+/HER2+ (B), HR-/HER2- (C) and HR-/HER2+ (D) tumors.

In this paper, we present Goal-GAN, an interpretable and end-to-end trainable model for human trajectory prediction. Inspired by human navigation, we model the task of trajectory prediction as an intuitive two-stage process: (i) goal estimation, which predicts the most likely target positions of the agent, followed by a (ii) routing module which estimates a set of plausible trajectories that route towards the estimated goal. We leverage information about the past trajectory and visual context of the scene to estimate a multi-modal probability distribution over the possible goal positions, which is used to sample a potential goal during the inference. The routing is governed by a recurrent neural network that reacts to physical constraints in the nearby surroundings and generates feasible paths that route towards the sampled goal. Our extensive experimental evaluation shows that our method establishes a new state-of-the-art on several benchmarks while being able to generate a realistic and diverse set of trajectories that conform to physical constraints.

Additional file 4: Figure S3. Difference between tumor size according to imaging and residual tumor size versus residual tumor size. Data are shown for all patients with both MRI and US (A) and for HR+/HER2+ (B), HR-/HER2- (C) and HR-/HER2+ tumors (D). Quadratic curve was fitted using the least squares method.

Additional file 3: Figure S2. Correlation between tumor size by imaging and pathological tumor size according to breast cancer subtype. Data are shown for tumor size estimations by (A) MRI in all patients with MRI, (B) US in all patients with US, (C) MRI and (D) US in patients with both MRI and US.

Additional file 1: Table S1. Prediction of pCR and residual tumor size in MRI and US group.

Breast cancer research 23(1), 36 (2021). doi:10.1186/s13058-021-01413-y, Published by BioMed Central, London