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Methodological quality of systematic reviews in dentistry including animal studies: a cross-sectional study
No full textBackground: The overall confidence in the results of systematic reviews including animal models can be heterogeneous. We assessed the methodological quality of systematic reviews including animal models in dentistry as well as the overall confidence in the results of those systematic reviews.
Material & methods: PubMed, Web of Science and Scopus were searched for systematic reviews including animal studies in dentistry published later than January 2010 until 18th of July 2022. Overall confidence in the results was assessed using a modified version of the A MeaSurement Tool to Assess systematic Reviews (AMSTAR-2) checklist. Checklist items were rated as 'yes, partial yes, no' and 'not applicable'. Linear regression analysis was used to investigate associations between systematic review characteristics and the overall adherence to the AMSTAR-2 checklist. The overall confidence in the results was calculated based on the number of critical and non-critical weaknesses presented in the AMSTAR-2 items and rated as high, moderate, low and critical low. Results: Of initially 951 retrieved systematic reviews, 190 were included in the study. The overall confidence in the results was low in 43 (22.6%) and critically low in 133 (70.0%) systematic reviews. While some AMSTAR-2 items were regularly reported (e.g. conflict of interest, selection in duplicate), others were not (e.g. funding: n = 1; 0.5%). Multivariable linear regression analysis showed that the adherence scores of AMSTAR-2 was significantly associated with publication year, journal impact factor (IF), topic, and the use of tools to assess risk of bias (RoB) of the systematic reviews. Conclusion: Although the methodological quality of dental systematic reviews of animal models improved over the years, it is still suboptimal. The overall confidence in the results was mostly low or critically low. Systematic reviews, which were published later, published in a journal with a higher IF, focused on non-surgery topics, and used at least one tool to assess RoB correlated with greater adherence to the AMSTAR-2 guidelines
Molecular and functional characterisation of the phosphatidylethanolamine-binding protein (PEBP)-family in Dioscorea polystachya with special emphasis on the tuber-inducing properties of DpFT-like3
No full textYams (Dioscorea ssp.) sind Knollenpflanzen, die vornehmlich in tropischen und sub-tropischen Gebieten abgebaut werden. Trotz kommerzieller Relevanz ist über die Knollenentwicklung in Yams wenig bekannt.
In der Entwicklung von Speicherorganen von Kartoffeln und Zwiebeln spielt das Protein FLOWERING LOCUS T (FT), Teil der phosphatidyletanolamine-binding protein Familie (PEBP), eine Rolle.
In dieser Dissertation wurde die PEBP-Familie, insbesondere FT in der chinesischen Yam (Dioscorea polystachya) untersucht.
Insgesamt wurden 17 verschiedene PEBPs identifiziert, von denen neun der FT-Untergruppe zugeordnet werden konnten.
Sequenz- und Expressionsanalysen führten zur Auswahl von DpFT-like3 als Kandidat für weitere Untersuchungen.
Überexpressionsstudien von DpFT-like3 in A. thaliana und S. tuberosum deuten auf eine induzierende Rolle von DpFT-like3 in der Knollenbildung in der chinesischen Yam hin.Yams (Dioscorea ssp.) are tuberous plants, mainly grown in tropical and sub-tropical regions. Despite their commercial relevance, few informations are published about the molecular development of their tubers.
The protein FLOWERING LOCUS T (FT), member of the phosphatidyletanolamine-binding protein family (PEBP), plays a role in the development of storage organs of potato and onion.
In this dissertation, the PEBP-family, especially the FT-subclade, was investigated in Chinese Yam (Dioscorea polystachya).
Overall, 17 different PEBPs, nine of which belonged to the FT-subclade, were identified.
Sequence- and expressionanalyses led to the selection of DpFT-like3 as a candidate for further investigation.
Overexpression of DpFT-like3 in A. thaliana and S. tuberosum indicate a potential inducing role of DpFT-like3 in the tuber development of Chinese yam
The Classification of Purely Infinite C*-Algebras Using Kasparov’s Theory
No full textNach Eberhard Kirchbergs Tod im August 2022 hat seine Ehefrau Sommai freundlicherweise zugestimmt, das vorliegende Manuskript der mathematischen Öffentlichkeit zugänglich zu machen. Dieses Werk war gedacht als ein vollständiges Werk zur Klassifikation rein unendlicher C*-Algebren. Es enthält eine große Fülle von tiefen Resultaten, Ideen und Techniken, wurde aber vom Autor nicht vollständig fertiggestellt. Es ist hier in dem Zustand, wie es auf seinem Computer vorgefunden wurde. Lediglich ein von James Gabe und Mikael Rørdam erstellter einführender Text wurde hinzugefügt.After Eberhard Kirchberg's passing in August 2022, his wife, Sommai, graciously agreed to make this manuscript available to the mathematical community. This work was intended to serve as the definitive book on purely infinite C*-algebras and their classification. It contains a wealth of deep results, ideas, and techniques, but the manuscript is not completely finished. It remains in the form in which it was found on Kirchberg's computer, with no alterations made. But it comes with an additional explanatory text by James Gabe and Mikael Rørdam
Verification of asynchronous hyperproperties
No full textHyperproperties sind ein unter anderem für Sicherheitsanalysen relevantes Konzept zur Beschreibung von Systemeigenschaften, die verschiedene Ausführungen miteinander in Beziehung setzen. Viele aktuelle Ansätze zur formalen Verifikation von Hyperproperties haben jedoch einige Einschränkungen: In den genutzten Spezifikationslogiken sind nicht alle omega-regulären Eigenschaften ausdrückbar, Spezifikationen sind synchron, schreiten also auf allen Ausführungen im gleichen Tempo voran, und die meisten Verifikationsverfahren nutzen Systemmodelle mit endlichem Zustandsraum, die zwar für Hardware-, aber nicht Softwaresysteme, adäquat sind. In dieser Arbeit werden drei temporale Hyperlogiken zur Spezifikation von omega-regulären und asynchronen Hyperproperties sowie ein neues Automatenmodell zur Analyse von asynchronen Hyperpropties eingeführt. Dann werden das Model Checking und Erfüllbarkeitsproblem der neuen Logiken sowie ihre Ausdruckskraft untersucht.Hyperproperties are a concept for describing system properties that are captured by interactions between different executions. Recently, it has gained attention e.g. due to its relevance for security analyses. Many current approaches to the formal verification of hyperproperties have some drawbacks, however: The utilised specification logics cannot express all omega-regular properties, specifications are synchronous, i.e. traverse all executions in lockstep, and most verification techniques use finite state system models which are adequate for hardware, but not software systems. In this thesis, we introduce three temporal hyperlogics for the specification of omega-regular and asynchronous hyperproperties as well as a new automaton model for the analysis of asynchronous hyperproperties. Then, we investigate the model checking and satisfiability problem of the new logics as well as their expressivity
Activity of tafasitamab in combination with rituximab in subtypes of aggressive lymphoma
No full textBackground: Despite recent advances in the treatment of aggressive lymphomas, a significant fraction of patients still succumbs to their disease. Thus, novel therapies are urgently needed. As the anti-CD20 antibody rituximab and the CD19-targeting antibody tafasitamab share distinct modes of actions, we investigated if dual-targeting of aggressive lymphoma B-cells by combining rituximab and tafasitamab might increase cytotoxic effects. Methods: Antibody single and combination efficacy was determined investigating different modes of action including direct 'cytotoxicity', antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) in 'in vitro' and 'in vivo' models of aggressive B-cell lymphoma comprising diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL). Results: Three different sensitivity profiles to antibody monotherapy or combination treatment were observed in 'in vitro' models: while 1/11 cell lines was primarily sensitive to tafasitamab and 2/11 to rituximab, the combination resulted in enhanced cell death in 8/11 cell lines in at least one mode of action. Treatment with either antibody or the combination resulted in decreased expression of the oncogenic transcription factor MYC and inhibition of AKT signaling, which mirrored the cell line-specific sensitivities to direct cytotoxicity. At last, the combination resulted in a synergistic survival benefit in a PBMC-humanized Ramos NOD/SCID mouse model. Conclusion: This study demonstrates that the combination of tafasitamab and rituximab improves efficacy compared to single-agent treatments in models of aggressive B-cell lymphoma 'in vitro' and 'in vivo'
A systematic review of handover actions in human dyads
No full textIntroduction: Handover actions are joint actions in which an object is passed from one actor to another. In order to carry out a smooth handover action, precise coordination of both actors’ movements is of critical importance. This requires the synchronization of both the kinematics of the reaching movement and the grip forces of the two actors during the interaction. Psychologists, for example, may be interested in studying handover actions in order to identify the cognitive mechanisms underlying the interaction of two partners. In addition, robotic engineers may utilize insights from sensorimotor information processing in human handover as models for the design controllers in robots in hybrid (human-robot) interaction scenarios. To date, there is little knowledge transfer between researchers in different disciplines and no common framework or language for the study of handover actions. Methods: For this reason, we systematically reviewed the literature on human-human handover actions in which at least one of the two types of behavioral data, kinematics or grip force, was measured. Results: Nine relevant studies were identified. The different methodologies and results of the individual studies are here described and contextualized. Discussion: Based on these results, a common framework is suggested that, provides a distinct and straightforward language and systematics for use in future studies. We suggest to term the actors as giver and receiver, as well as to subdivide the whole action into four phases: (1) Reach and grasp, (2) object transport, (3) object transfer, and (4) end of handover to comprehensively and clearly describe the handover action. The framework aims to foster the necessary exchange between different scientific disciplines to promote research on handover actions. Overall, the results support the assumption that givers adapt their executions according to the receiver’s intentions, that the start of the release of the object is processed feedforward and that the release process is feedback-controlled in the transfer phase. We identified the action planning of the receiver as a research gap
Bloodstream infections in a rural hospital in Sierra Leone: a retrospective database study
No full textBackground. The health system in Sierra Leone has limited infrastructure to provide data on the epidemiology of infectious diseases and to inform clinical decision-making. The diagnostic and research laboratory capacity at Masanga Teaching Hospital was systematically expanded with microbiology infrastructure-building as one of the centrepieces. Objective. This study aims to report the spectrum of bacterial pathogens from bloodstream infections (BSIs) in a rural hospital in Sierra Leone during the first year after the implementation of a blood culture infrastructure and characterize the detected antimicrobial resistances. Patients and methods. Patients treated at Masanga Hospital (Sierra Leone, March 2023–March 2024) were included in this database analysis if they were tested for BSI (BD BACTEC). Demographic and medical data were recorded for each patient. Antimicrobial susceptibility testing was done following EUCAST clinical guidelines. Results. Of the 340 blood cultures, 34 (10%) were positive for obligate pathogens. The three most frequent pathogens were 'Escherichia coli' (n=8), followed by 'Burkholderia cepacia' complex (n=7) and 'Salmonella enterica' (n=5). Almost all 'Klebsiella pneumoniae' (n=3/3) and 'E. coli' (n=7/8) were resistant to third-generation cephalosporins. All four 'Staphylococcus aureus' isolates were methicillin susceptible (mecA negative). Carbapenem resistance was detected in 'Acinetobacter baumannii' complex (blaNDM)
Conclusion. The proportion of positive blood cultures with obligate pathogens (10%) was within the suggested benchmark (5–15%). Gram-negative bacteria dominated the pathogen spectrum of BSI with high resistance rates to third-generation cephalosporins
Can the Dose Constraints Be Trusted? Actual Dose Exposure of Bladder and Rectum During Prostate Cancer Radiotherapy
No full textBackground/Objectives: The actual daily dose distribution during image-guided radiotherapy (IGRT) for prostate cancer (PCa) deviates from the planned due to positional and volumetric changes in the patient’s body and organs at risk (OAR). This study investigates the difference between planned and delivered dose, by calculating the actual daily dose to bladder and rectum for each radiotherapy fraction. The impact of OAR volumes on dose distribution and the correlation with treatment-related toxicities will be evaluated. Methods: A cone-beam computed tomography (CBCT) based daily dose calculation was performed for a total of 821 CBCT scans of 20 patients with localized PCa treated with IGRT. Each fraction’s dose-volume histogram was analyzed, and toxicities were correlated with OAR dose exposures. Results: Daily dosimetric evaluation showed a significant increase in bladder V65–V70 and rectum V50–V70 compared to planned values (p ≤ 0.003 each). In contrast to bladder Dmean, the rectum Dmean was significantly increased (0.47 vs. 0.55; p < 0.001). For the bladder an exponential dose-volume relationship was demonstrated, while no dose-volume relationship was found for the rectum. On average, patients with increased genitourinary toxicities received significantly increased bladder Dmean (0.44 vs. 0.63, p = 0.014). Conclusions: Conventional dose evaluation via a summation plan rather underestimates daily dosimetric parameters. For adaptive radiotherapy of PCa, volumetric parameters rather than mean doses should be used for daily treatment planning constraints. Because established dose constraints cannot be reduced to a single fraction, reasonable dose constraints should consider daily positional and volumetric changes, rather than relying on a single planning CT
Characterization of pre-existing anti-PEG and anti-AGAL antibodies towards PRX-102 in patients with Fabry disease
No full textPolyethylene glycol (PEG)ylated drugs are used for medical treatment, since PEGylation either decreases drug clearance or/and shields the protein from undesirable immunogenicity. PEGylation was implemented in a new enzyme replacement therapy for Fabry disease (FD), pegunigalsidase-alfa (PRX-102). However, exposure to PEG via life-style products and vaccination can result in the formation of anti-PEG antibodies. We demonstrate the 'de novo' formation of functional anti-PEG antibodies in a healthy male after the second mRNA-based vaccination against SARS-CoV-2. Consequently, we analyzed the frequency and inhibitory function of anti-PEG and anti-α-Galactosidase A (AGAL) antibodies in 102 FD patients (46.9% males). We identified 29 out of 87 (33.3%) patients with low anti-PEG titers. Sera from patients without anti-AGAL antibodies [n=70] showed a higher rescued AGAL activity of agalsidase-beta and PRX-102 [both p<0.0001] compared to those with anti-AGAL antibodies [n=15]. Sera from anti-AGAL antibody-negative and -positive patients had less inhibitory effects on PRX-102 (rescued activity: 89 ± 6% versus 85 ± 7% and 49 ± 26% versus 25 ± 32%; both p<0.0001). Enzyme stability assays demonstrated that AUCs in anti-AGAL-negative sera (n=20) were 7.6-fold higher for PRX-102, while AUCs of both enzymes in anti-AGAL-positive sera (n=6) were decreased. However, AUC for PRX-102 was 33% of non-anti-AGAL-positive sera treated PRX-102 and 5-fold higher compared to agalsidase-beta. Anti-PEG antibodies had no significant effects on serum half-life of PRX-102, probably due to low titers. Conceivably, therapy efficacy may be superior under next-generation PRX-102 therapy compared to current enzyme replacement therapies in terms of reduced inhibitory effects of anti-AGAL and minor inhibitory effects of anti-PEG antibodies
COL6A1 als prognostischer Faktor bei der Akuten Myeloischen Leukämie
No full textTrotz intensiver zytostatischer Therapie hat die Akute Myeloische Leukämie (AML) eine schlechte Prognose. Im Rahmen subtypenspezifischer Therapieansätze werden aktuell vor allem Oberflächenproteine als Targets adressiert. Jedoch ist auch das Mikroumfeld von der Erkrankung betroffen, zum Beispiel ist Kollagen Typ VI im leukämischen Knochenmark hochreguliert. In anderen Krebsentitäten konnte bereits ein Einfluss auf die Prognose und Chemoresistenz durch direkte oder indirekte Interaktionen mit der Krebszelle belegt werden. In dieser Arbeit konnte bestätigt werden, dass eine erhöhte Expression von Kollagen Typ VI im Knochenmark von AML-Erkrankten mit einem schlechteren Gesamtüberleben, ereignisfreien Überleben und einer höheren Rezidivrate nach Erreichen einer CR assoziiert ist. Somit kann Kollagen Typ VI als prognostischer Faktor dienen. Durch die vorhandene Blutstromexposition und Hochregulierung wäre aber auch ein Therapieansatz mit Kollagen Typ VI selbst als mögliches Target möglich