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  • 1
    In: Agronomy, MDPI AG, Vol. 11, No. 9 ( 2021-08-27), p. 1710-
    Abstract: The search for approaches to a holistic sustainable agriculture requires the development of new cropping systems that provide additional ecosystem services beyond biomass supply for food, feed, material, and energy use. The reduction of chemical synthetic plant protection products is a key instrument to protect vulnerable natural resources such as groundwater and biodiversity. Together with an optimal use of mineral fertilizer, agroecological practices, and precision agriculture technologies, a complete elimination of chemical synthetic plant protection in mineral-ecological cropping systems (MECSs) may not only improve the environmental performance of agroecosystems, but also ensure their yield performance. Therefore, the development of MECSs aims to improve the overall ecosystem services of agricultural landscapes by (i) improving the provision of regulating ecosystem services compared to conventional cropping systems and (ii) improving the supply of provisioning ecosystem services compared to organic cropping systems. In the present review, all relevant research levels and aspects of this new farming concept are outlined and discussed based on a comprehensive literature review and the ongoing research project “Agriculture 4.0 without Chemical-Synthetic Plant Protection”.
    Type of Medium: Online Resource
    ISSN: 2073-4395
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2607043-1
    SSG: 23
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  • 2
    In: Molecules, MDPI AG, Vol. 27, No. 1 ( 2021-12-26), p. 121-
    Abstract: Food contact materials (FCMs) can transfer chemicals arising from their manufacture to food before consumption. Regulatory frameworks ensure consumer safety by prescribing methods for the assessment of FCMs that rely on migration testing either into real-life foods or food simulants. Standard migration testing conditions for single-use FCMs are justifiably conservative, employing recognized worst-case contact times and temperatures. For repeated-use FCMs, the third of three consecutive tests using worst-case conditions is taken as a surrogate of the much shorter contact period that often occurs over the service life of these items. Food contact regulations allow for the use of migration modelling for the chemicals in the FCM and for the partitioning that occurs between the FCM and food/simulant during prolonged contact, under which steady-state conditions are favored. This study demonstrates that the steady-state is rarely reached under repeated-use conditions and that partitioning plays a minor role that results in migration essentially being diffusion controlled. Domains of use have been identified within which partitioning does not play a significant role, allowing modelling based upon diffusion parameters to be used. These findings have the potential to advance the modelling of migration from repeated-use articles for the benefit of regulatory guidance and compliance practices.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2008644-1
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  • 3
    In: Nanomaterials, MDPI AG, Vol. 9, No. 1 ( 2018-12-22), p. 11-
    Abstract: Synthetic amorphous silica (SAS) constitute a large group of industrial nanomaterials (NM). Based on their different production processes, SAS can be distinguished as precipitated, fumed, gel and colloidal. The biological activity of SAS, e.g., cytotoxicity or inflammatory potential in the lungs is low but has been shown to depend on the particle size, at least for colloidal silica. Therefore, the preparation of suspensions from highly aggregated or agglomerated SAS powder materials is critical. Here we analyzed the influence of ultrasonic dispersion energy on the biologic activity of SAS using NR8383 alveolar macrophage (AM) assay. Fully characterized SAS (7 precipitated, 3 fumed, 3 gel, and 1 colloidal) were dispersed in H2O by stirring and filtering through a 5 µm filter. Aqueous suspensions were sonicated with low or high ultrasonic dispersion (USD) energy of 18 or 270 kJ/mL, respectively. A dose range of 11.25–90 µg/mL was administered to the AM under protein-free conditions to detect particle-cell interactions without the attenuating effect of proteins that typically occur in vivo. The release of lactate dehydrogenase (LDH), glucuronidase (GLU), and tumor necrosis factor α (TNF) were measured after 16 h. Hydrogen peroxide (H2O2) production was assayed after 90 min. The overall pattern of the in vitro response to SAS (12/14) was clearly dose-dependent, except for two SAS which showed very low bioactivity. High USD energy gradually decreased the particle size of precipitated, fumed, and gel SAS whereas the low adverse effect concentrations (LOECs) remained unchanged. Nevertheless, the comparison of dose-response curves revealed slight, but uniform shifts in EC50 values (LDH, and partially GLU) for precipitated SAS (6/7), gel SAS (2/3), and fumed SAS (3/3). Release of TNF changed inconsistently with higher ultrasonic dispersion (USD) energy whereas the induction of H2O2 was diminished in all cases. Electron microscopy and energy dispersive X-ray analysis showed an uptake of SAS into endosomes, lysosomes, endoplasmic reticulum, and different types of phagosomes. The possible effects of different uptake routes are discussed. The study shows that the effect of increased USD energy on the in vitro bioactivity of SAS is surprisingly small. As the in vitro response of AM to different SAS is highly uniform, the production process per se is of minor relevance for toxicity.
    Type of Medium: Online Resource
    ISSN: 2079-4991
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2662255-5
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  • 4
    In: Cancers, MDPI AG, Vol. 15, No. 15 ( 2023-07-25), p. 3774-
    Abstract: Overcoming PARPi resistance is a high clinical priority. We established and characterized comparative in vitro models of acquired PARPi resistance, derived from either a BRCA1-proficient or BRCA1-deficient isogenic background by long-term exposure to olaparib. While parental cell lines already exhibited a certain level of intrinsic activity of multidrug resistance (MDR) proteins, resulting PARPi-resistant cells from both models further converted toward MDR. In both models, the PARPi-resistant phenotype was shaped by (i) cross-resistance to other PARPis (ii) impaired susceptibility toward the formation of DNA-platinum adducts upon exposure to cisplatin, which could be reverted by the drug efflux inhibitors verapamil or diphenhydramine, and (iii) reduced PARP-trapping activity. However, the signature and activity of ABC-transporter expression and the cross-resistance spectra to other chemotherapeutic drugs considerably diverged between the BRCA1-proficient vs. BRCA1-deficient models. Using dual-fluorescence co-culture experiments, we observed that PARPi-resistant cells had a competitive disadvantage over PARPi-sensitive cells in a drug-free medium. However, they rapidly gained clonal dominance under olaparib selection pressure, which could be mitigated by the MRP1 inhibitor MK-751. Conclusively, we present a well-characterized in vitro model, which could be instrumental in dissecting mechanisms of PARPi resistance from HR-proficient vs. HR-deficient background and in studying clonal dynamics of PARPi-resistant cells in response to experimental drugs, such as novel olaparib-sensitizers.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527080-1
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  • 5
    In: Journal of Clinical Medicine, MDPI AG, Vol. 12, No. 1 ( 2022-12-27), p. 192-
    Abstract: Background: Elevated serum ferritin is a common condition in critically ill patients. It is well known that hyperferritinemia constitutes a good biomarker for hemophagocytic lymphohistiocytosis (HLH) in critically ill patients. However, further differential diagnoses of hyperferritinemia in adult critically ill patients remain poorly investigated. We sought to systematically investigate hyperferritinemia in adult critically ill patients without HLH. Methods: In this secondary analysis of a retrospective observational study, patients ≥18 years admitted to at least one adult intensive care unit at Charité–Universitätsmedizin Berlin between January 2006 and August 2018, and with hyperferritinemia of ≥500 μg/L were included. Patients with HLH were excluded. All patients were categorized into non-sepsis, sepsis, and septic shock. They were also classified into 17 disease groups, based on their ICD-10 codes, and pre-existing immunosuppression was determined. Uni- and multivariable linear regression analyses were performed in all patients. Results: A total of 2583 patients were analyzed. Multivariable linear regression analysis revealed positive associations of maximum SOFA score, sepsis or septic shock, liver disease (except hepatitis), and hematological malignancy with maximum ferritin. T/NK cell lymphoma, acute myeloblastic leukemia, Kaposi’s sarcoma, acute or subacute liver failure, and hepatic veno-occlusive disease were positively associated with maximum ferritin in post-hoc multivariable linear regression analysis. Conclusions: Sepsis or septic shock, liver disease (except hepatitis) and hematological malignancy are important differential diagnoses in hyperferritinemic adult critically ill patients without HLH. Together with HLH, they complete the quartet of important differential diagnoses of hyperferritinemia in adult critically ill patients. As these conditions are also related to HLH, it is important to apply HLH-2004 criteria for exclusion of HLH in hyperferritinemic patients. Hyperferritinemic critically ill patients without HLH require quick investigation of differential diagnoses.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662592-1
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  • 6
    In: Materials, MDPI AG, Vol. 13, No. 5 ( 2020-03-07), p. 1203-
    Abstract: Extensive efforts were undertaken to develop suitable biomaterials for tissue engineering (TE) applications. To facilitate clinical approval processes and ensure the success of TE applications, bioinspired concepts are currently focused on. Working on bone tissue engineering, we describe in the present study a method for biofunctionalization of collagen/hydroxyapatite composites with BMP-2 mimetic peptides. This approach is expected to be fundamentally transferable to other tissue engineering fields. A modified BMP-2 mimetic peptide containing a negatively charged poly-glutamic acid residue (E7 BMP-2 peptide) was used to bind positively charged hydroxyapatite (HA) particles by electrostatic attraction. Binding efficiency was biochemically detected to be on average 85% compared to 30% of BMP-2 peptide without E7 residue. By quartz crystal microbalance (QCM) analysis, we could demonstrate the time-dependent dissociation of the BMP-2 mimetic peptides and the stable binding of the E7 BMP-2 peptides on HA-coated quartz crystals. As shown by immunofluorescence staining, alkaline phosphatase expression is similar to that detected in jaw periosteal cells (JPCs) stimulated with the whole BMP-2 protein. Mineralization potential of JPCs in the presence of BMP-2 mimetic peptides was also shown to be at least similar or significantly higher when low peptide concentrations were used, as compared to JPCs cultured in the presence of recombinant BMP-2 controls. In the following, collagen/hydroxyapatite composite materials were prepared. By proliferation analysis, we detected a decrease in cell viability with increasing HA ratios. Therefore, we chose a collagen/hydroxyapatite ratio of 1:2, similar to the natural composition of bone. The following inclusion of E7 BMP-2 peptides within the composite material resulted in significantly elevated long-term JPC proliferation under osteogenic conditions. We conclude that our advanced approach for fast and cost-effective scaffold preparation and biofunctionalization is suitable for improved and prolonged JPC proliferation. Further studies should prove the functionality of composite scaffolds in vivo.
    Type of Medium: Online Resource
    ISSN: 1996-1944
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2487261-1
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  • 7
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 18, No. 5 ( 2021-03-08), p. 2739-
    Abstract: Briefly before the first peak of the COVID-19 pandemic in Berlin, Germany, schools closed in mid-March 2020. Following re-opening, schools resumed operation at a reduced level for nine weeks. During this phase, we aimed at assessing, among students and teachers, infection status, symptoms, individual behaviour, and institutional infection prevention measures. Twenty-four primary and secondary school classes, randomly selected across Berlin, were examined. Oro-nasopharyngeal swabs and capillary blood samples were collected to determine SARS-CoV-2 infection (PCR) and specific IgG (ELISA), respectively. Medical history, household characteristics, leisure activities, fear of infection, risk perception, hand hygiene, facemask wearing, and institutional preventive measures were assessed. Descriptive analysis was performed. Among 535 participants (385 students, 150 staff), one teenager was found to be infected with SARS-CoV-2 (0.2%), and seven individuals exhibited specific IgG (1.3%). Compared to pre-pandemic times, screen time (e.g., TV, gaming, social media) increased, and the majority of primary school students reported reduced physical activity (42.2%). Fear of infection and risk perception were relatively low, acceptance of adapted health behaviors was high. In this post-lockdown period of low SARS-CoV-2 incidence in Berlin, individual and school-level infection prevention measures were largely adhered to. Nevertheless, vigilance and continued preventive measures are essential to cope with future pandemic activity.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2175195-X
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  • 8
    Online Resource
    Online Resource
    MDPI AG ; 2021
    In:  International Journal of Environmental Research and Public Health Vol. 18, No. 18 ( 2021-09-08), p. 9467-
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 18, No. 18 ( 2021-09-08), p. 9467-
    Abstract: Background: There is an urgent need to systematically analyze the growing body of literature on the effect of motor imagery (MI) training in children and adolescents. Methods: Seven databases and clinicaltrials.gov were searched. Two reviewers independently screened references and full texts, and extracted data (studies’ methodology, MI elements, temporal parameters). Two studies were meta-analyzed providing the standard mean difference (SDM). Selected studies were evaluated with the risk of bias (RoB) and GRADE tools. Results: A total of 7238 references were retrieved. The sample size of the 22 included studies, published between 1995 and 2021, ranged from 18 to 136 participants, totaling 934 (nine to 18 years). Studies included healthy pupils, mentally retarded adolescents, children with motor coordination difficulties or with mild mental disabilities. The motor learning tasks focused on upper, lower and whole body movements. SMDs for the primary outcome of pooled studies varied between 0.83 to 1.87 (95% CI, I2, T2 varied 0.33–3.10; p = 0.001; 0–74%; 0–0.59). RoB varied between some concerns and high risk. GRADE rating was low. Conclusions: MI combined with physical practice (PP) might have a high potential for healthy and impaired children and adolescents. However, important reporting recommendations (PETTLEP, TIDieR, CONSORT) should be followed. The systematic review was registered with PROSPERO: CRD42021237361.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2175195-X
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