Nanohydrogels combine advantages of hydrogels and nanoparticles. In particular, they represent promising drug delivery systems. Nanogel synthesis by oxidative condensation of polyglycidol ...prepolymers, that are modified with thiol groups, results in crosslinking by disulfide bonds. Hereby, biomolecules like the antidiabetic peptide RS1‐reg, derived from the regulatory protein RS1 of the Na+‐D‐glucose cotransporter SGLT1, can be covalently bound by cysteine residues to the nanogel in a hydrophilic, stabilizing environment. After oral uptake, the acid‐stable nanogels protect their loading during gastric passage from proteolytic degradation. Under alkaline conditions in small intestine the nanohydrogels become mucoadhesive, pass the intestinal mucosa and are taken up into small intestinal enterocytes by endocytosis. Using Caco‐2 cells as a model for small intestinal enterocytes, by confocal laser scanning microscopy and structured illumination microscopy, the colocalization of fluorescent‐labeled RS1‐reg with markers of endosomes, lysosomes, and trans‐Golgi‐network after uptake with polyglycidol‐based nanogels formed by precipitation polymerization is demonstrated. This indicates that RS1‐reg follows the endosomal pathway. In the following, the design of bespoken nanohydrogels for specific targeting of RS1‐reg to its site of action at the trans‐Golgi network is described that might also represent a way of targeted transport for other drugs to their targets at the Golgi apparatus.
The design of polyglycidol‐based nanohydrogels for selective organelle targeting of therapeutic agents is reported with the example of the targeted retrograde transport of the antidiabetic peptide RS1‐reg to its site of action at the trans‐Golgi network, demonstrating that endosomal escape is not always required for specific intracellular drug transport.
A novel complex featuring a mesoionic carbene Fe2(CO)5(trz)(?-pdt) (1) (trz = 1-phenyl-l,3-methyl,4-butyl-1,2,3-triazol-5-ylidene), was synthesized and spectroscopically and structurally ...characterized. The reductive behaviour of this compound in the
presence and in the absence of acid (CH3CO2H) was examined by cyclic voltammetry (CV) that revealed the lack of efficient activity towards proton reduction.
Nanosecond pulsed two-beam laser interference is used to generate two-dimensional temperature patterns on a magnetic thin film sample. We show that the original domain structure of a Co/Pd multilayer ...thin film changes drastically upon exceeding the Curie temperature by thermal demagnetization. At even higher temperatures the multilayer system is irreversibly changed. In this area no out-of-plane magnetization can be found before and after a subsequent ac-demagnetization. These findings are supported by numerical simulations using the Landau-Lifshitz-Bloch formalism which shows the importance of defect sites and anisotropy changes to model the experiments. Thus, a one-dimensional temperature pattern can be transferred into a magnetic stripe pattern. In this way one can produce magnetic nanowire arrays with lateral dimensions of the order of 100 nm. Typical patterned areas are in the range of several square millimeters. Hence, the parallel direct laser interference patterning method of magnetic thin films is an attractive alternative to the conventional serial electron beam writing of magnetic nanostructures.
Abstract
As part of ROBDEKON, a 24-ton crawler excavator was equipped with sensors and a digital actuation interface as a technology demonstrator which features autonomy capabilities. The system ...architecture includes algorithms for localization, perception, mapping, planning, and control. The system is capable of tasks like autonomous driving to a target location, excavation of a predefined area to a given depth, and autonomous loading of an autonomously approaching transport vehicle. To ensure safety, collision avoidance based on 360° perception is always active during autonomous operation. This article presents the concept and implementation of the excavator’s autonomy functionality.
Gastric cancer (GC) represents one of the most fatal neoplasms in gastrointestinal oncology and affected patients can only hope for cure in limited disease. In a metastatic situation however, ...patients have a worse prognosis finally resulting in cancer-related death. Some improvements were made by using intensified chemotherapy such as the FLOT protocol (5-FU, leucovorin, oxaliplatin and docetaxel). However, a breakthrough in the treatment of advanced GC has been achieved by pre-therapeutical tumor analysis for potentially targetable alterations. Microsatellite instability, PD-L1 expression, Epstein Barr virus, and human epidermal growth factor receptor-2 (HER2) overexpression or amplification are the most beneficial targets, if addressed, can prolong survival in a palliative situation. Whether the combination of these targeted therapeutics with chemotherapy can bring long-term survival or even a chance of cure in a metastatic situation is not clear. Here, we report the case of a 30-year-old man with GC and extensive metastases who was cured by anti-HER2 antibody Trastuzumab combined with the FLOT regime. Initial staging showed an exophytic Siewert type III tumor and extensive hepatic metastases. Histology resulted in gastric adenocarcinoma with HER2 overexpression (2+, FISH positive). Twelve courses of chemotherapy comprising Trastuzumab and FLOT were administered. After treatment, the extensive liver metastases had disappeared with no evidence of residual tumor growth on the CT scans. Monotherapy of Trastuzumab was continued until gastrectomy with D2 lymph node dissection and probing of liver tissue, which revealed no residual tumor cells. Five years after surgery, there is continued complete remission. In conclusion, Trastuzumab in combination with FLOT may have curative potential even for metastatic stages of HER-2-positive GC.
The aim of this study was to assess quantitative ultra-high b-value (UHB) diffusion magnetic resonance imaging (MRI)-derived parameters in comparison to standard clinical apparent diffusion ...coefficient (SD-ADC-2b-1000, SD-ADC-2b-1500) for the prediction of clinically significant prostate cancer, defined as Gleason Grade Group greater than or equal to 2.
Seventy-three patients who underwent 3-T prostate MRI with diffusion-weighted imaging acquired at b = 50/500/1000/1500s/mm2 and b = 100/500/1000/1500/2250/3000/4000 s/mm2 were included. Magnetic resonance lesions were segmented manually on individual sequences, then matched to targeted transrectal ultrasonography/MRI fusion biopsies. Monoexponential 2-point and multipoint fits of standard diffusion and of UHB diffusion were calculated with incremental b-values. Furthermore, a kurtosis fit with parameters Dapp and Kapp with incremental b-values was obtained. Each parameter was examined for prediction of clinically significant prostate cancer using bootstrapped receiver operating characteristics and decision curve analysis. Parameter models were compared using Vuong test.
Fifty of 73 men (age, 66 years interquartile range, 61-72; prostate-specific antigen, 6.6 ng/mL interquartile range, 5-9.7) had 64 MRI-detected lesions. The performance of SD-ADC-2b-1000 (area under the curve, 0.82) and SD-ADC-2b-1500 (area under the curve, 0.82) was not statistically different (P = 0.99), with SD-ADC-2b-1500 selected as reference. Compared with the reference model, none of the 19 tested logistic regression parameter models including multipoint and 2-point UHB-ADC, Dapp, and Kapp with incremental b-values of up to 4000 s/mm2 outperformed SD-ADC-2b-1500 (all P's > 0.05). Decision curve analysis confirmed these results indicating no higher net benefit for UHB parameters in comparison to SD-ADC-2b-1500 in the clinically important range from 3% to 20% of cancer threshold probability. Net reduction analysis showed no reduction of MR lesions requiring biopsy.
Despite evaluation of a large b-value range and inclusion of 2-point, multipoint, and kurtosis models, none of the parameters provided better predictive performance than standard 2-point ADC measurements using b-values 50/1000 or 50/1500. Our results suggest that most of the diagnostic benefits available in diffusion MRI are already represented in an ADC composed of one low and one 1000 to 1500 s/mm2 b-value.
Background and purpose
The effects of the coronavirus disease 2019 (COVID‐19) pandemic on telemedical care have not been described on a national level. Thus, we investigated the medical stroke ...treatment situation before, during, and after the first lockdown in Germany.
Methods
In this nationwide, multicenter study, data from 14 telemedical networks including 31 network centers and 155 spoke hospitals covering large parts of Germany were analyzed regarding patients' characteristics, stroke type/severity, and acute stroke treatment. A survey focusing on potential shortcomings of in‐hospital and (telemedical) stroke care during the pandemic was conducted.
Results
Between January 2018 and June 2020, 67,033 telemedical consultations and 38,895 telemedical stroke consultations were conducted. A significant decline of telemedical (p < 0.001) and telemedical stroke consultations (p < 0.001) during the lockdown in March/April 2020 and a reciprocal increase after relaxation of COVID‐19 measures in May/June 2020 were observed. Compared to 2018–2019, neither stroke patients' age (p = 0.38), gender (p = 0.44), nor severity of ischemic stroke (p = 0.32) differed in March/April 2020. Whereas the proportion of ischemic stroke patients for whom endovascular treatment (14.3% vs. 14.6%; p = 0.85) was recommended remained stable, there was a nonsignificant trend toward a lower proportion of recommendation of intravenous thrombolysis during the lockdown (19.0% vs. 22.1%; p = 0.052). Despite the majority of participating network centers treating patients with COVID‐19, there were no relevant shortcomings reported regarding in‐hospital stroke treatment or telemedical stroke care.
Conclusions
Telemedical stroke care in Germany was able to provide full service despite the COVID‐19 pandemic, but telemedical consultations declined abruptly during the lockdown period and normalized after relaxation of COVID‐19 measures in Germany.
Telemedical stroke care in Germany was able to provide full service despite the COVID‐19 pandemic, but telemedical consultations declined abruptly during the lockdown period and normalized after relaxation of COVID‐19 measures in Germany. Although the majority of the participating network centers treated COVID‐19 patients, relevant shortcomings regarding telemedical stroke care were not reported. Our representative nationwide study demonstrates the robustness of teleconsultation services in Germany during the COVID‐19 pandemic in the first half of 2020.
Introduction
Knee cartilage lesions are very frequent in arthroscopic surgery. This multi-center-study was aimed to evaluate the distribution and possible associated factors of these pathologies in ...more than 1000 patients.
Materials and methods
The German cartilage registry (KnorpelRegister DGOU) started in 2013. In this paper, we present the baseline-data (distribution of knee cartilage lesions and the demographic data) of more than 1000 cases since the registries’ start-up.
Results
A total number of 47 centers were involved into this multicenter study. A total of 1071 patients primary were registered. Degenerative knees 629 times (61.8 %) and injured knees 302 times (29.6 %) were involved. In the remaining 89 knees (8.7 %) the genesis of cartilage lesions was unclear. Single defects were observed in 792 cases (77.6 %). Most frequently the medial femoral condyle or the patella was affected. In 78 knees (7.6 %) the main-defect was associated with a defect of the corresponding joint surface. In the remaining cases complex cartilage damages were found.
Conclusions
Our results are in confirmation with other multicenter studies. But these former studies did not differentiate into traumatic and degenerative lesions. Furthermore no characteristics were given regarding to single, kissing or complex lesions. Thus this database will be a sufficient instrument for the investigation of the “natural course” of cartilage lesions, but above all about the effectiveness of different treatment options.
All‐perovskite tandem solar cells show great potential to enable the highest performance at reasonable costs for a viable market entry in the near future. In particular, wide‐bandgap (WBG) ...perovskites with higher open‐circuit voltage (VOC) are essential to further improve the tandem solar cells’ performance. Here, a new 1.8 eV bandgap triple‐halide perovskite composition in conjunction with a piperazinium iodide (PI) surface treatment is developed. With structural analysis, it is found that the PI modifies the surface through a reduction of excess lead iodide in the perovskite and additionally penetrates the bulk. Constant light‐induced magneto‐transport measurements are applied to separately resolve charge carrier properties of electrons and holes. These measurements reveal a reduced deep trap state density, and improved steady‐state carrier lifetime (factor 2.6) and diffusion lengths (factor 1.6). As a result, WBG PSCs achieve 1.36 V VOC, reaching 90% of the radiative limit. Combined with a 1.26 eV narrow bandgap (NBG) perovskite with a rubidium iodide additive, this enables a tandem cell with a certified scan efficiency of 27.5%.
W e present a new 1.80 eV wide‐bandgap (WBG) perovskite treated with piperazinium iodide (PI) for all‐perovskite tandem solar cells. This treatment eliminates non‐radiative recombination losses and reduces defect density resulting in an open circuit voltage of 1.36 V and enhanced photostability. Combined with a narrow bandgap (NBG) perovskite, this enables a tandem cell with a certified scan efficiency of 27.5%.
PDF
