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A synthetic sponge system against miRNAs of the miR-17/92 cluster targets transcriptional MYC dosage compensation in aneuploid cancer
No full textBackground: Genomic instability, a hallmark of cancer, leads to copy number variations disrupting gene dosage balance and contributing to tumor progression. One of the most affected oncogenes is MYC, whose overexpression is tightly regulated to avoid cytotoxicity. In aneuploid cancer cells, gene dosage compensation mechanisms involving microRNAs (miRNAs) from the miR-17/92 cluster contribute in regulating MYC expression. Targeting this miRNA-mediated compensation system represents a promising therapeutic strategy leading to an uncontrolled and lethal MYC overexpression. Results: Synthetic miRNA sponges targeting miR-17, miR-19a, and miR-20a, key regulators of MYC dosage compensation, were designed and validated. Breast cancer cells (MCF7) with stable exogenous MYC overexpression were used to assess the impact of sponge constructs on MYC regulation. Quantitative RT-PCR revealed a significant reduction in miRNA expression and a corresponding increase in endogenous MYC levels upon sponge treatment. Functional assays in multiple colorectal cancer cell lines with varying MYC copy numbers demonstrated a time-dependent increase in cell death following sponge transfection. Cytotoxic effects increased with MYC copy number, confirming a correlation between gene dosage sensitivity and therapeutic response. Conclusions: Our findings demonstrate that miRNA sponges targeting the miR-17/92 cluster can effectively disrupt MYC dosage compensation, leading to selective cytotoxicity in MYC-amplified cancer cells
The effectiveness of e-learning in focused cardiac ultrasound training : a prospective controlled study
No full textIntroduction
Focused Cardiac Ultrasound (FOCUS) is an essential tool for rapid cardiac assessment across various clinical subspecialties. Consequently, teaching foundational FOCUS skills is of critical importance. This study investigates the effectiveness of e-learning in imparting FOCUS skills.
Materials and methods
This prospective, controlled study assessed competency development among medical students attending a FOCUS workshop (study group) at two time points: T1 (pre-training) and T2 (post-training, after completing e-learning). The competence gain of the group was compared to a reference group (control group) of physicians who had also used the e-learning in preparation for a certified FOCUS workshop. Objective competencies were measured at both time points using short-answer and multiple-choice theory tests. Subjective self-assessments of competencies and opinions of the e-learning were investigated through evaluation forms at T2 using a 7-point Likert scale (1 = strongly disagree, 7 = strongly agree). Demographic information was collected at T1, and user behaviour during e-learning was assessed at T2. Primary endpoints were the increase in theoretical competencies (study group) and the comparison of subjective and objective competency levels (study vs. reference).
Results
A total of 104 participants (study group = 48; reference group = 56) were included. The study group exhibited a significant (p < 0.001) increase in theoretical competencies. However, at T2 the reference group achieved significantly higher theoretical test scores (p < 0.001). One influencing factor was previous practical experience (p = 0.02), which was significantly higher in the reference group (p < 0.001). Both groups estimated their competency at the end of preparation to be at similar levels (4.3 ± 0.9 scalepoints [SP] versus 4.3 ± 1.0 SP; p = 0.94). Evaluation results of the e-learning were positive in both groups (5.8 ± 0.9 SP versus 6.2 ± 0.7 SP; p = 0.04), with results in the reference group being significantly higher.
Conclusion
Both the improvement in competencies and the positive reception of digital learning media should encourage the increased implementation of e-learning formats. This study shows that such formats in ultrasound training can effectively complement face-to-face workshops and should be included in certified training curricula
Das Jahr 2024 am i3mainz
No full textBericht über das i3mainz, Institut für Raumbezogene Informations- und Messtechnik im Jahr 2024: seine Projekte, das Team, die Zusammenarbeit mit der Fachrichtung Angewandte Informatik und Geodäsie der Hochschule Mainz und den Partnern aus Wissenschaft, Wirtschaft und Gesellschaft.
Im Fokus 2024: Altern auf dem Land: Mit Raumintelligenz zu integrierten Lösungen.87 Seite
Retrospektive, bizentrische, klinische Nachuntersuchung des Straumann-BLX-Implantatsystems
No full textDentale Implantate sind aus der modernen Zahnmedizin nicht mehr wegzudenken. Die Firma Straumann hat zu diesem Zweck für das Sofortimplantationskonzept das BLX-Implantatsystem entwickelt. Die Überlebensrate dieser Implantate an der Klinik und Poliklinik für Mund-, Kiefer- und Gesichtschirurgie - Plastische Operationen der Universitätsmedizin der Johannes Gutenberg-Universität Mainz sowie einer zahnärztlichen Praxis in Bad Soden wurde in Hinblick auf patientenspezifische Parameter, Implantatparameter und chirurgisches Vorgehen hin untersucht. Ebenfalls wurden röntgenologisch sichtbare Änderungen der marginalen Knochenhöhe erfasst.
Material und Methoden
Der Operationsplan der Abteilung für Mund-, Kiefer- und Gesichtschirurgie- plastische Operationen der Johannes Gutenberg-Universität Mainz sowie der Praxis in Bad Soden wurde im Zeitraum von 2018 bis 2021 auf Implantationen des BLX-Implantatsystems durchsucht, patientenspezifische, implantatspezifische sowie operationsspezifische Parameter analysiert und in Bezug zur Überlebensrate gestellt. Zudem wurde die radiologisch sichtbare, marginale Knochenhöhe idealerweise postprothetisch sowie in der 1-Jahres Verlaufskontrolle ermittelt und die Differenz analysiert.
Ergebnisse
Als statistisch signifikant für das Implantatüberleben, auch nach Bonferronikorrektur, wurden der Implantatdurchmesser, die Antibiotikagabe, der Zeitpunkt der Augmentation (ein- oder zweizeitig) sowie das Auftreten einer Periimplantitis im Behandlungsverlauf identifiziert. Es stellte sich keine Art, Dauer und kein Präparat der Antibiose einem anderen Konzept gegenüber überlegen dar.
Die einzeitige Augmentation war in dieser Untersuchung dem zweizeitigen Vorgehen signifikant überlegen.
Andere untersuchte Zusammenhänge wiesen keine oder, nach Korrekturverfahren, keine statistisch signifikanten Zusammenhänge mehr auf.
Die Überlebensrate liegt mit 94,2% bei ähnlichen Werten wie vergleichbare Studien, der marginale Knochenabbau im Mittelwert bei 0,17mm mit einer Standartabweichung von 0,5mm, teilweise ist auch ein Knochenzuwachs zu verzeichnen.
Diskussion
Die festgestellten Zusammenhänge decken sich in weiten Teilen mit der bereits vorliegenden Datenlage oder können mit der Zusammensetzung des Patientenkollektivs in der Stichprobe erklärt werden. Einzig der Implantatdurchmesser wurde in keiner der zugrundeliegenden Quellen als relevanter Risikofaktor für einen Implantatmisserfolg im Sinne eines Verlustes identifiziert. An dieser Stelle sei einzuwenden, dass die Stichprobe recht klein und das Patientenklientel aufgrund der Überweiserfunktion der Universitätsmedizin nicht als repräsentative Stichprobe gelten kann. Mit 40 Monaten ist der Nachbeobachtungszeitraum der Implantate nicht so hoch wie in anderen Studien, daher ist die Beurteilung der marginalen Knochenhöhenänderung nur vorsichtig zu treffen. Insgesamt stellt sich das BLX-System in diesem Zusammenhang als gutes Implantatsystem dar, das seinem Indikationsgebiet entsprechend zur oralen Rehabilitation als Alternative zu anderen Implantatsystemen eingesetzt werden kann.X, 102 Seiten ; Illustrationen, Diagramm
A microscale thermophoresis-based enzymatic RNA methyltransferase assay enables the discovery of DNMT2 inhibitors
No full textRNA methyltransferases (MTases) have recently become increasingly important in drug discovery. Yet, most frequently utilized RNA MTase assays are limited in their throughput and hamper this rapidly evolving field of medicinal chemistry. This study developed a microscale thermophoresis (MST)-based split aptamer assay for enzymatic MTase investigations, improving current methodologies by offering a non-proprietary, cost-effective, and highly sensitive approach. Our findings demonstrate the assay’s effectiveness across different RNA MTases, including inhibitor characterization of METTL3/14, DNMT2, NSUN2, and S. aureus TrmD, enabling future drug discovery efforts. Using this concept, a pilot screening on the cancer drug target DNMT2 discovered several hit compounds with micromolar potency
Temperature-dependent study of the spin dynamics of coupled Y3Fe5O12/Gd3Fe5O12/Pt trilayers
No full textWe combine ferromagnetic resonance absorption measurements (FMR) with spin pumping measurements to ascertain the full magnetization dynamics of Y3Fe5O12 (YIG)/Gd3Fe5O12 (GdIG)/Pt heterostructures. This trilayer system offers the unique possibility to individually investigate the spin dynamics of the ferrimagnetic GdIG close to its compensation temperature. We show that this trilayer acts as a highly tunable spin current source and our experimental results are corroborated by micromagnetic simulations. The detected spin current in the top Pt layer is governed by spin dynamics in the GdIG layer, while the broadband FMR absorption spectrum of the full heterostructure comprises contributions from spin dynamics in both layers. Thus, combining the measurements of FMR absorption and spin current generation from the spin pumping and spin Seebeck effect allows us to understand the spin dynamics contributions of both constituents
Micro-computed tomographic analysis of the morphology of maxillary canines
No full textObjective: This study aimed to examine the morphology of maxillary canines (MxCs) by means of micro-computed tomography (micro-CT). Materials and methods: The root canal configurations (RCCs) of 97 maxillary canines of a mixed Swiss-German population were analyzed using micro-CT. After representing the internal morphology by 3-D software imaging, the RCC results were described using a four-digit system code indicating the main root canal from coronal to apical thirds and the main foramina number. Results: The most frequently observed RCCs of the MxC of the Swiss-German population were 1-1-1/1 (77.3%), followed by 1-1-1/2 (14.4%), 1-1-2/2 (4.1%), and finally 1-1-1/3 and 1-2-1/1 with 2.1% each. One physiological foramen was observed in 79.4% of the samples, two in 18.6%, and only 2.1% had three foramina. In 52.6% of the MxC samples, accessory and connecting canals were identified, with the majority located in the apical third of the root. Conclusions: This study contributes detailed information about the RCCs of MxC. The most prevalent RCC is 1-1-1/1, with accessory or connecting canals present in over half of the samples. However, it is noteworthy that in more than one-fifth of the examined samples, a particularly challenging RCC was observed. This should be considered when selecting treatment techniques. Clinical relevance: This study presents the root canal configurations in maxillary canines of a Swiss-German population and emphasizes the importance of influencing endodontic treatment decisions and outcomes
Health-related internet use and cyberchondria in adolescents : population-based cross-sectional survey
No full textBackground: Health-related internet searches are widespread among the general population. Cyberchondria, that is, excessive health-related internet research that leads to emotional stress, showed significant associations with personality traits and psychological symptoms in adult samples. Although adolescents exhibit high levels of internet use, strong interest in health topics, and heightened vulnerability to anxiety symptoms and anxiety disorders, little research has examined cyberchondria in this age group.
Objective: Based on findings from adult populations, this study is among the first to investigate cyberchondria in adolescents and its associations with psychological traits (intolerance of uncertainty and health anxiety) and symptoms (problematic internet use and compulsive behavior). In addition, we examined whether intolerance of uncertainty moderates the relationship between cyberchondria and health anxiety.
Methods: A cross-sectional, web-based survey was conducted between April and July 2023 among adolescents (N=159; 14‐17 years, mean 15.9, SD 0.88 years; 54% male, 45% female, 1% diverse). Validated self-report questionnaires were used to assess cyberchondria, intolerance of uncertainty, health anxiety, problematic internet use, and compulsive symptoms.
Results: Overall, 83% (132/159) reported searching for health-related topics on the internet. On average, they spent 8.68 minutes per day on health-related internet use (mean 8.68, SD 11.57), within a total of 238 daily minutes per day on total internet use (mean 238.3, SD 103.84). Cyberchondria showed strong positive correlations with health anxiety (r=0.54; P≤.001), problematic internet use (r=0.50; P≤.001), compulsive behavior (r=0.47; P≤.001), and intolerance of uncertainty (r=0.55; P≤.001). The moderation analysis revealed a significant overall model (∆R2=8.08%, F3, 155=38.26; P≤.001), but intolerance of uncertainty was not a significant moderator (∆R2<.01%, F1, 155=0.79; P=.38, 95% CI −0.01 to 0.03).
Conclusions: The results suggest that health-related internet research and cyberchondria seem to be as relevant in adolescence as they are in adulthood, with similar associations to psychological traits and symptoms. The findings particularly support theoretical models that emphasize the role of intolerance of uncertainty and health anxiety. From a practical perspective, recognizing cyberchondria in adolescence could inform early prevention and psychoeducational strategies, especially given the high prevalence of health-related information seeking on the internet among adolescents. Further longitudinal research is needed to clarify causal pathways and to evaluate possible intervention approaches
The TropoPause Composition TOwed Sensor Shuttle (TPC-TOSS) : a new airborne dual platform approach for atmospheric composition measurements at the tropopause
No full textIn this paper we introduce the new TropoPause Composition TOwed Sensor Shuttle (TPC-TOSS), which constitutes an advanced development of the AIRcraft TOwed Sensor Shuttle (AIRTOSS), introduced by Frey et al. (2009). As part of a tandem measurement platform with a Learjet 35A, both platforms were equipped with redundant instruments for co-located measurements of aerosol size distribution (Ultra-High Sensitivity Aerosol Spectrometer, UHSAS), ozone (2BTech model 205), cloud particles (Back-Scatter Cloud Probe, BCP), as well as relative humidity, temperature and pressure. To measure the exact position of the two platforms as well as the relative distance of the TPC-TOSS to the Learjet a Global Positioning System (GPS) is installed on both platforms. Two identical Inertial Navigation Systems (INS) further allow to monitor attitude angles (roll, pitch, and heading) and accelerations. Laboratory tests before and ground tests as well as in-flight tests during the intensive operation period show a good agreement of the ozone and temperature measurements of better than 4.2 ppbv +1.1 % (ozone) and 0.5 °C (temperature) at a noise level of ± (2 ppbv + 0.5 %) for 2 s data (ozone) and ± 0.1 K for 1 Hz data (temperature). Stability of the ozone monitor mounted in the TPC-TOSS has been tested and is estimated to be 2.2 ppbv (offset, 1σ) and 0.7 % (gain, 1σ), respectively, based on the drift of offset and gain during regular calibrations between measurement flights in the two weeks operation period. The new TPC-TOSS was successfully flown during the TPEx I (TropoPause composition gradients and mixing Experiment) mission in June 2024 and performed four flights covering the altitude range between 6.4 and 10.9 km. The tropopause was crossed several times as evident from different temperature and ozone gradients as well as gradients of the aerosol number concentration. With the setup we are able to resolve transient stability and composition gradients ranging from almost zero or even negative to strong positive gradients of up to 25 K km−1 for potential temperature and from inverted to strong positive vertical gradients of ozone of up to 800 ppbv km−1, respectively. These gradients are caused by transport and mixing due to convection or shear induced turbulence at the tropopause
Degree formula for the discriminant divisor of lagrangian fibrations of irreducible symplectic manifolds
No full textLet be an irreducible holomorphic symplectic manifold with a Lagrangian
fibration , whose discriminant locus is
. This thesis defines weights
such that
where is the polarization type of .
The definition of the involves the cohomology sheaves of the
complex
and this thesis gives an in-depth analysis of those sheaves.
Furthermore, the definition involves the choice of a Kähler form
on , which induces a polarization of type on the
smooth fibers of . To show that the do not depend on the choice
of is the main undertaking of this thesis.
If the characteristic cycle over is compact, then
one can define the weights as
In case of non-compact characteristic cycles one can choose an appropriate
compact subcycle to compute in
the same way.73 Seiten ; Illustratione