Comparative Analysis of the Visual, Refractive and Aberrometric Outcome with the Use of 2 Intraocular Refractive Segment Multifocal Lenses

To demonstrate the results of ray tracing higher- and lower-order aberrations in pseudophakic eyes with rotationally asymmetrical segment multifocal lenses, total high- and low-order aberrations, measured by root mean square value (RMS), refraction, uncorrected distance and uncorrected near visual acuity (UCDVA and UCNVA), and tear break-up time, were measured at scotopic size in 42 eyes of patients implanted with bifocal refractive Mplus15/Mplus30 IOL with +1.5 dpt near addition (42 eyes of patients implanted with Mplus15)/+3.0 dpt near addition (91 eyes of patients implanted with Mplus30), and 107 eyes of control group. No significant differences were noticed between the examined groups concerning UCDVA, UCNVA, and tear break-up time (p < 0.001). Coma and total high-order aberrations were significantly higher for the Mplus30 lens in comparison to the Mplus15 lens and the control group (Coma, Trefoil p < 0.001, Secondary Astigmatism p = 0.002). The spherical aberrations were significantly higher in the lower-addition lens (p = 0.016) in comparison to the control group and to the higher-addition lens group (p < 0.001). Both intraocular lens models were successful at reaching refractive aim, good distance, and near function with the lower higher-order aberrations for the low-addition lens

Cilostazol Stimulates Angiogenesis and Accelerates Fracture Healing in Aged Male and Female Mice by Increasing the Expression of PI3K and RUNX2

Fracture healing in the aged is associated with a reduced healing capacity, which often results in delayed healing or non-union formation. Many factors may contribute to this deterioration of bone regeneration, including a reduced ‘angiogenic trauma response’. The phosphodiesterase3 (PDE-3) inhibitor cilostazol has been shown to exert pro-angiogenic and pro-osteogenic effects in preclinical studies. Therefore, we herein analyzed in a stable closed femoral fracture model whether this compound also promotes fracture healing in aged mice. Forty-two aged CD-1 mice (age: 16–18 months) were daily treated with 30 mg/kg body weight cilostazol (n = 21) or vehicle (control, n = 21) by oral gavage. At 2 and 5 weeks after fracture, the femora were analyzed by X-ray, biomechanics, micro-computed tomography (µCT), histology, immunohistochemistry, and Western blotting. These analyses revealed a significantly increased bending stiffness at 2 weeks (2.2 ± 0.4 vs. 4.3 ± 0.7 N/mm) and an enhanced bone formation at 5 weeks (4.4 ± 0.7 vs. 9.1 ± 0.7 mm3 ) in cilostazol-treated mice when compared to controls. This was associated with a higher number of newly formed CD31-positive microvessels (3.3 ± 0.9 vs. 5.5 ± 0.7 microvessels/HPF) as well as an elevated expression of phosphoinositide-3-kinase (PI3K) (3.6 ± 0.8 vs. 17.4 ± 5.5-pixel intensity × 104 ) and runt-related transcription factor (RUNX)2 (6.4 ± 1.2 vs. 18.2 ± 2.7-pixel intensity × 104 ) within the callus tissue. These findings indicate that cilostazol accelerates fracture healing in aged mice by stimulating angiogenesis and the expression of PI3K and RUNX2. Hence, cilostazol may represent a promising compound to promote bone regeneration in geriatric patients

A Case Study of the Use of Smart EV Charging for Peak Shaving in Local Area Grids

Electricity storage systems, whether electric vehicles or stationary battery storage systems, stabilize the electricity supply grid with their flexibility and thus drive the energy transition forward. Grid peak power demand has a high impact on the energy bill for commercial electricity consumers. Using battery storage capacities (EVs or stationary battery systems) can help to reduce these peaks, applying peak shaving. This study aims to address the potential of peak shaving using a PV plant and smart unidirectional and bidirectional charging technology for two fleets of electric vehicles and two comparable configurations of stationary battery storage systems on the university campus of Saarland University in Saarbrücken as a case study. Based on an annual measurement of the grid demand power of all consumers on the campus, a simulation study was carried out to compare the peak shaving potential of seven scenarios. For the sake of simplicity, it was assumed that the vehicles are connected to the charging station during working hours and can be charged and discharged within a user-defined range of state of charge. Furthermore, only the electricity costs were included in the profitability analysis; investment and operating costs were not taken into account. Compared to a reference system without battery storage capacities and a PV plant, the overall result is that the peak-shaving potential and the associated reduction in total electricity costs increases with the exclusive use of a PV system (3.2%) via the inclusion of the EV fleet (up to 3.0% for unidirectional smart charging and 8.1% for bidirectional charging) up to a stationary battery storage system (13.3%)

Expression of 3q Oncogene SEC62 Predicts Survival in Head and Neck Squamous Cell Carcinoma Patients Treated with Primary Chemoradiation

Primary chemoradiotherapy (CRT) is an established treatment option for locally advanced head and neck squamous cell carcinomas (HNSCC) usually combining intensity modified radiotherapy with concurrent platinum-based chemotherapy. Though the majority of patients can be cured with this regimen, treatment response is highly heterogeneous and can hardly be predicted. SEC62 represents a metastasis stimulating oncogene that is frequently overexpressed in various cancer entities and is associated with poor outcome. Its role in HNSCC patients undergoing CRT has not been investigated so far. A total of 127 HNSCC patients treated with primary CRT were included in this study. The median follow-up was 5.4 years. Pretherapeutic tissue samples of the primary tumors were used for immunohistochemistry targeting SEC62. SEC62 expression, clinical and histopathological parameters, as well as patient outcome, were correlated in univariate and multivariate survival analyses. High SEC62 expression correlated with a significantly shorter overall survival (p = 0.015) and advanced lymph node metastases (p = 0.024). Further significant predictors of poor overall and progression-free survival included response to therapy (RECIST1.1), nodal status, distant metastases, tobacco consumption, recurrence of disease, and UICC stage. In a multivariate Cox hazard proportional regression analysis, only SEC62 expression (p = 0.046) and response to therapy (p < 0.0001) maintained statistical significance as independent predictors of the patients’ overall survival. This study identified SEC62 as an independent prognostic biomarker in HNSCC patients treated with primary CRT. The role of SEC62 as a potential therapeutic target and its interaction with radiation-induced molecular alterations in head and neck cancer cells should further be investigated

Effects on cardiorespiratory fitness of moderate-intensity training vs. energy-matched training with increasing intensity

Introduction: The present study investigated the role of training intensity in the dose–response relationship between endurance training and cardiorespiratory fitness (CRF). The hypothesis was that beginners would benefit from an increase in training intensity after an initial training phase, even if the energy expenditure was not altered. For this purpose, 26 weeks of continuous moderate training (control group, CON) was compared to training with gradually increasing intensity (intervention group, INC) but constant energy expenditure. Methods: Thirty-one healthy, untrained subjects (13 men, 18 women; 46 ± 8 years; body mass index 25.4 ± 3.3 kg m−2 ; maximum oxygen uptake, VO2max 34 ± 4 ml min−1 kg−1 ) trained for 10 weeks with moderate intensity [3 days/ week for 50 min/session at 55% heart rate reserve (HRreserve)] before allocation to one of two groups. A minimization technique was used to ensure homogeneous groups. While group CON continued with moderate intensity for 16 weeks, the INC group trained at 70% HRreserve for 8 weeks and thereafter participated in a 4 × 4 training program (high-intensity interval training, HIIT) for 8 weeks. Constant energy expenditure was ensured by indirect calorimetry and corresponding adjustment of the training volume. Treadmill tests were performed at baseline and after 10, 18, and 26 weeks. Results: The INC group showed improved VO2max (3.4 ± 2.7 ml kg−1 min−1 ) to a significantly greater degree than the CON group (0.4 ± 2.9 ml kg−1 min−1 ) (P = 0.020). In addition, the INC group exhibited improved Vmax (1.7 ± 0.7 km h−1 ) to a significantly greater degree than the CON group (1.0 ± 0.5 km h−1 ) (P = 0.001). The reduction of resting HR was significantly larger in the INC group (7 ± 4 bpm) than in the CON group (2 ± 6 bpm) (P = 0.001). The mean heart rate in the submaximal exercise test was reduced significantly in the CON group (5 ± 6 bpm; P = 0.007) and in the INC group (8 ± 7 bpm; P = 0.001), without a significant interaction between group and time point

Safety and Efficacy of Selective Internal Radionuclide Therapy with 90Y Glass Microspheres in Patients with Progressive Hepatocellular Carcinoma after the Failure of Repeated Transarterial Chemoembolization

Transarterial chemoembolization (TACE) is currently the standard of care in patients with unresectable hepatocellular carcinoma (HCC), and selective internal radionuclide therapy (SIRT) with 90Y microspheres is mainly used as an alternative modality in patients considered poor candidates for TACE. Treatment with sorafenib is the recommended option for patients with progressive disease after TACE. This study aims to evaluate the safety and efficacy of SIRT with glass microspheres in patients with progressive HCC after repeated TACE who are not eligible for treatment with sorafenib. Forty-seven patients with progressive HCC after a median of three TACE sessions (range 2–14) underwent SIRT (3.5 ± 1.5 GBq; liver target dose 110–120 Gy). Toxicity was recorded 4 and 12 weeks after treatment and reported according to the Common Terminology Criteria for Adverse Events Version 5.0. Treatment response was assessed three months after SIRT using multiphase computed tomography and modified criteria in solid tumors (mRECIST). Survival analyses were performed using Kaplan–Meier curves and a Cox proportional hazards model for uni- and multivariate analyses. Significant but reversible hepatotoxicity (≥grade 3) occurred in five patients (11%). No radioembolization-induced liver disease (REILD) was observed. The number of previous TACE sessions and cumulative administered activity did not predict the incidence of postSIRT significant hepatotoxicity. Treatment responses consisted of partial responses in 26 (55%), stable disease in 12 (26%), and progressive disease in 9 (19%) patients. The median overall survival (OS) was 11 months (95% confidence interval (CI), 9–13), and objective responses to SIRT were associated with a longer OS (p = 0.008). Significant hepatotoxicity (≥grade 3) after SIRT was a contributor to impaired survival (median OS 6 months (95% CI, 4–8) vs. 12 months (95% CI, 10–14), p < 0.001). SIRT with glass microspheres is a safe and effective salvage treatment for patients with progressive HCC refractory to TACE who are considered poor candidates for sorafenib treatment

Biochemical and transcriptomic evaluation of a 3D lung organoid platform for pre-clinical testing of active substances targeting senescence

Chronic lung diseases such as chronic obstructive pulmonary disease and cystic fibrosis are incurable. Epithelial senescence, a state of dysfunctional cell cycle arrest, contributes to the progression of such diseases. Therefore, lung epithelial cells are a valuable target for therapeutic intervention. Here, we present a 3D airway lung organoid platform for the preclinical testing of active substances with regard to senescence, toxicity, and inflammation under standardized conditions in a 96 well format. Senescence was induced with doxorubicin and measured by activity of senescence associated galactosidase. Pharmaceutical compounds such as quercetin antagonized doxorubicininduced senescence without compromising organoid integrity. Using single cell sequencing, we identified a subset of cells expressing senescence markers which was decreased by quercetin. Doxorubicin induced the expression of detoxification factors specifically in goblet cells independent of quercetin. In conclusion, our platform enables for the analysis of senescence-related processes and will allow the pre-selection of a wide range of compounds (e.g. natural products) in preclinical studies, thus reducing the need for animal testing

Projektbericht: Summa Cum Fraude – Wissenschaftliches Fehlverhalten und der Versuch einer Gegenoffensive. Öffentlicher Teil

Das Projekt befasste sich mit der zentralen Fragestellung, inwieweit die bestehenden Mechanismen zur Selbstkontrolle in der Wissenschaft in der Lage sind, wissenschaftlichem Fehlverhalten effektiv entgegenzuwirken. Es wurden 207 Fälle von wissenschaftlichem Fehlverhalten ausführlich dokumentiert und an die betroffenen Verlage gemeldet. Dabei kamen nur solche Fälle zur Meldung, bei denen die Indikatoren für wissenschaftliches Fehlverhalten eindeutig waren (z.B. war die Manipulation von Daten mit bloßem Auge erkennbar). Leider hat sich schnell herausgestellt, dass selbst in diesen eindeutigen Fällen das tatsächliche Handeln durch die Journale von den in den ethischen Grundsätzen der Verlage formulierten Richtlinien zum Umgang mit wissenschaftlichem Fehlverhalten in der Mehrzahl der Fälle nahezu diametral abweicht. In vielen Fällen kann von einem Handeln nicht einmal die Rede sein, da Journale selbst auf wiederholte Meldungen desselben Falles von wissenschaftlichem Fehlverhalten nicht reagieren. In dieser Hinsicht kann die eigentliche Frage, inwieweit die Mechanismen zur Selbstkontrolle in der Wissenschaft tragfähig sind, prinzipiell nicht oder nur zu einem Teil beantwortet werden, da diese Mechanismen durch die Verweigerungshaltung vieler Journale gar nicht erst zum Einsatz kommen. So gesehen scheint es auch fraglich, ob zusätzliche Maßnahmen, die auf Grundlage der aus diesem Projekt hervorgegangenen Erfahrungen formuliert werden sollten, die Situation merklich verbessern könnten, da sie den Maßnahmenkatalog, der von Journalen nach wie vor ignoriert werden wird, allenfalls aufblähen. Neben diesen ernüchternden Befunden aufseiten der Journale war auch auf Seiten der sich fehlverhaltenden Autoren wenig Erfreuliches zu festzustellen. In nicht seltenen Fällen ist bei einigen Autorengruppen wissenschaftliches Fehlverhalten tägliche Praxis. Bei der Recherche von Fachartikeln mit manipuliertem Datenmaterial hat es sich fast schon zum Regelfall entwickelt, dass die Durchsicht der Publikationslisten einer einmal auffällig gewordenen Autorengruppe weiteres unlauteres Datenmaterial zutage bringt. Wenn zu den o.a. 207 Fällen alleine ein Autor mit mehr als 30 Fällen beiträgt, so kann man sagen, dass wissenschaftliches Fehl-verhalten stellenweise das Fundament einzelner Karrieren bildet. Flankierend gaben zehn Expert*innen in Interviews Vorschläge zur Verbesserung des Umgangs mit fragwürdigen Publikationen ab. Genannt wurden Beratung, Transparenz, Workshops zur Wissenschaftsethik und zur Identifikation fragwürdiger Inhalte, Open Science-Praktiken (z.B. Prä-Registrierung, Open Access zu Daten, Open Review), verbindliche Richtlinien und Monitoring von Retractions. Bibliotheken wurden besonders als Vermittler von Publikationskompetenz erwähnt. Allerdings wurde von den Expert*innen das gravierende Problem der Nicht-Reaktion der Journale kaum mit Verbesserungsvorschlägen bedacht.The project addressed the central issue of the extent to which existing mechanisms for self-regulation in science are effective in countering scientific misconduct. A total of 207 cases of scientific misconduct were thoroughly documented and reported to the relevant publishers. Only cases with clear indicators of scientific misconduct, such as visibly manipulated data, were reported. Unfortunately, it quickly became apparent that even in these clear cases, the actions taken by journals deviated significantly from the ethical guidelines outlined in their principles regarding scientific misconduct. In many instances, the journals did not even respond to repeated reports of the same case of scientific misconduct. This raises the fundamental question of the viability of self-regulation mechanisms in science, as these mechanisms are often not even utilized due to the resistant attitude of many journals. Thus, it remains questionable whether additional measures formulated based on the findings of this project could significantly improve the situation, as they might merely expand the catalogue of actions that journals continue to disregard. Aside from these disheartening findings regarding journals, there were also discouraging observations concerning authors engaged in misconduct. In some author groups, scientific misconduct has become a routine practice. When researching articles with manipulated data, it has almost become routine to uncover further instances of dubious data in the publication lists of author groups that have previously attracted attention. If a single author contributes to more than 30 out of the aforementioned 207 cases, it is evident that scientific misconduct forms the foundation of certain career trajectories. In parallel, ten experts provided suggestions for improving the handling of questionable publications through interviews. Recommendations included consultation, transparency, work-shops on scientific ethics and content identification, Open Science practices (such as pre-registration, open data access, and open review), binding guidelines, and retraction monitoring. Libraries were particularly highlighted as educators in publication competence. However, the experts scarcely addressed the significant issue of journals' non-responsiveness with proposals for improvement.Deutsche Forschungsgemeinschaft (DFG

Familial context influences media usage in 0- to 4-year old children

Background: The use of digital media (e.g., smartphones, tablets, etc.) and the Internet have become omnipresent for every age group and are part of children’s and parents’ everyday life. Focusing on young children, the availability of media devices, their use as well as associated problems (e.g., in social, emotional and motor development) have increased in recent years. Of particular interest for prevention of these problems in early childhood is the relationship between the familial context (parental digital media use, Problematic Internet Use, school graduation, presence of siblings) and the digital media use of infants and toddlers. The present study’s goal was to describe media usage in 0–4-year-old children and to identify the potential relationship between familial context factors and child media usage. Methods: The sample included N  =  3,035 children aged 0 to 3;11  years (M  = 17.37  months, SD  =  13.68; 49.13% female). Recruitment took place within the framework of a restandardization study for a German developmental test. The parents of the participants answered a questionnaire on socio-demographics, on child media use, and on parental media use. Questions on parental media use included the full version of the Short Compulsive Internet Use Scale (S-CIUS). Results: Significant increases in media usage times with child age were identified, but no significant gender differences. A multiple regression analysis revealed that increasing maternal total media usage time, a higher parental S-CIUS score, lower school leaving certificate of both mother and father, and increasing child’s age led to higher child media usage time. Having siblings diminished young children’s media usage in this study. Having more than one child and having children aged over a year was associated with a higher parental S-CIUS score. Conclusion: Family factors such as maternal media use time, Problematic Internet Use and lower school graduation are significantly associated with young children’s digital media use. Parents should be aware of their personal influence on their children’s media use which might be due their role in terms of model learning

A functional perspective on schema-based learning and recognition of novel word associations

With the current research, we sought to develop a functional perspective on schema-based learning of novel word associations, i.e., novel compound words and their later recognition. In combining the idea that both, schema-based learning (e.g., Hebscher et al., 2019; van Kesteren et al., 2012) and unitization (e.g., Bader et al., 2014; Haskins et al., 2008; see Henke, 2010) might rely less on hippocampal contribution than traditional associative learning, we hypothesized that schema-congruency might support the formation of unitized representations that could then be recognized by means of an absolute familiarity process (Mecklinger & Bader, 2020). All three experiments presented include an incidental learning phase, in which novel compound words were learned together with a preceding definition that was either congruent or neutral (experimental manipulation of schema congruency). After a retention interval of about 10 minutes, a surprise memory test followed. In the test phase, participants were shown different types of compound words and instructed to classify each as intact, recombined, or new (Exp. 1), as old (intact) or new (recombined, similar lures; Exp. 3) or underwent an implicit lexical decision task (Exp. 2). Our results imply that three processes might underly schema-based learning. Semantic priming, indicated by an N400 attenuation effect in the schema-congruent condition, establishes schema congruency. Condition-independent semantic integration of the constituents is beneficial for memory formation, as indicated by an N400 subsequent memory effect (SME). Lastly, we found a larger parietal SME in the congruent than in the neutral condition. This might reflect the formation of a conceptual (unitized) representation under the influence of a congruent schema. Second, based on our results, schema-congruency might support the formation of unitized representations, indicated by schema-congruency being more beneficial for associative than item memory performance (see Parks & Yonelinas, 2015). The neurocognitive processes underling recognition of those compound words might include larger absolute familiarity contributing to associative recognition in the congruent than in a neutral control condition, indicated by an N400 attenuation effect. Based on data from our third experiment including semantically similar distractors during the recognition memory test, we concluded that the representations formed under the influence of a schema might be gist-like. Those might be created next to episodic associations that are probably also formed in traditional associative learning. Lastly, those unitized memory representations formed under the influence of a schema cannot only be accessed in an explicit memory test, but also affect performance in an implicit memory test.Das Ziel der vorliegenden Arbeit war es, eine funktionelle Perspektive auf das schema-basierte Lernen neuer Wortassoziationen (Komposita) und deren späteres Wiedererkennen zu entwickeln. Dazu wurden zwei Forschungsideen zusammengeführt. Da sowohl schema-basiertes Lernen (z.B., Hebscher et al., 2019; van Kesteren et al., 2012) als auch Unitarisierung (z.B., Bader et al., 2014; Haskins et al., 2008; siehe auch Henke, 2010) weniger hippocampale Beteiligung aufweisen als traditionelles Assoziationslernen, formulierten wir die Hypothese, dass Schemakongruenz die Bildung unitarisierter Repräsentationen unterstützen könnte, die dann mittels eines absoluten Vertrautheitsprozesses wiedererkannt werden könnten (Mecklinger & Bader, 2020). Die drei Experimente, die in der vorliegenden Arbeit dargestellt sind, beinhalten alle eine inzidentelle Lernphase, in der neue Komposita zusammen mit einer kongruenten oder neutralen vorangehenden Definition gelernt wurden (experimentelle Manipulation von Schemakongruenz). Nach einem Retentionsintervall von etwa 10 Minuten folgte ein überraschender, nicht vorangekündigter Gedächtnistest. In dieser Testphase sahen die Teilnehmenden verschiedene Arten von Komposita und sollten diese als intakt, rekombiniert oder neu klassifizieren (Experiment 1), als alt (intakt) oder neu (rekombiniert, ähnliche Distraktoren; Experiment 3) oder bearbeiteten eine lexikalische Entscheidungsaufgabe (Experiment 2). Unsere Ergebnisse implizieren, dass drei Prozesse am schema-basiertem Lernen beteiligt sind. Semantisches Priming, angezeigt durch eine reduzierte N400 Amplitude in der schema-kongruenten Bedingungen, führt zu Schemakongruenz. Die bedingungsunabhängige semantische Integration der Wortbestandteile ist förderlich für die Gedächtnisbildung, indiziert durch einen N400 Subsequent Memory Effect (SME). Der dritte Prozess, die schemakongruenzgetriebene Bildung einer konzeptuellen (unitarisierten) Repräsentation wird angezeigt durch einen größeren parietalen SME in der kongruenten im Vergleich zur neutralen Bedingung. Basierend auf dem behavioralen Ergebnismuster, dass assoziatives Gedächtnis mehr von Schemakongruenz profitiert als Itemgedächtnis (siehe auch Parks & Yonelinas, 2015), könnte Schemakongruenz die Bildung von unitarisierten Repräsentationen fördern. Die neurokognitiven Prozesse, die dem Wiedererkennen solcher Komposita unterliegen, beinhalten wahrscheinlich einen höheren Anteil absoluter Vertrautheit in der kongruenten als in der neutralen Bedingung, indiziert durch einen entsprechenden reduzierten N400-Effekt. Basierend auf den Ergebnissen des dritten Experiments, bei dem der Rekognitionstest semantisch ähnliche Distraktoren beinhaltete, schlussfolgerten wir, dass die Repräsentationen, die unter dem Einfluss eines Schemas gebildet werden, detailarm sind und lediglich die semantische Konzeptstruktur (gist) beinhalten. Diese Repräsentationen könnten parallel zu episodischen Assoziationen geformt werden, die wahrscheinlich beim traditionellen Assoziationslernen gebildet werden. Die unitarisierten Repräsentationen konnten hierbei nicht nur in einem expliziten Gedächtnistest verwendet werden, sondern auch die Performanz in einer impliziten Gedächtnisaufgabe beeinflussen.Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) – Projektnummer 232722074 – SFB 1102, Projekt A6 / Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – Project-ID 232722074 – SFB 1102, Project A