bluuebunny/crossref_metadata_2025_split huggingface dataset:
Limited variation in microbial communities across populations of Macrosteles leafhoppers (Hemiptera: Cicadellidae)
Authors: Mulio Sandra Åhlén , Zwolińska Agnieszka , Klejdysz Tomasz , Prus‐Frankowska Monika , Michalik Anna , Kolasa Michał , Łukasik Piotr 
Published: June 2024

AbstractMicrobial symbionts play crucial roles in insect biology, yet their diversity, distribution, and temporal dynamics across host populations remain poorly understood. In this study, we investigated the spatio‐temporal distribution of bacterial symbionts within the widely distributed and economically significant leafhopper genus Macrosteles, with a focus on Macrosteles laevis. Using host and symbiont marker gene amplicon sequencing, we explored the intricate relationships between these insects and their microbial partners. Our analysis of the cytochrome oxidase subunit I (COI) gene data revealed several intriguing findings. First, there was no strong genetic differentiation across M. laevis populations, suggesting gene flow among them. Second, we observed significant levels of heteroplasmy, indicating the presence of multiple mitochondrial haplotypes within individuals. Third, parasitoid infections were prevalent, highlighting the complex ecological interactions involving leafhoppers. The 16S rRNA data confirmed the universal presence of ancient nutritional endosymbionts—Sulcia and Nasuia—in M. laevis. Additionally, we found a high prevalence of Arsenophonus, another common symbiont. Interestingly, unlike most previously studied species, M. laevis exhibited only occasional cases of infection with known facultative endosymbionts and other bacteria. Notably, there was no significant variation in symbiont prevalence across different populations or among sampling years within the same population. Comparatively, facultative endosymbionts such as Rickettsia, Wolbachia, Cardinium and Lariskella were more common in other Macrosteles species. These findings underscore the importance of considering both host and symbiont dynamics when studying microbial associations. By simultaneously characterizing host and symbiont marker gene amplicons in large insect collections, we gain valuable insights into the intricate interplay between insects and their microbial partners. Understanding these dynamics contributes to our broader comprehension of host–microbe interactions in natural ecosystems.
Airway epithelial overexpressed cathepsin K induces airway remodelling through epithelial–mesenchymal trophic unit activation in asthma
Authors: Qin Ling , Yao Ye , Wang Weijie , Qin Qingwu , Liu Jingjing , Liu Huijun , Yuan Lin , Yuan Yunchang , Du Xizi , Zhao Bingrong , Wu Xinyu , Qing Bei , Huang Leng , Wang Gang , Xiang Yang , Qu Xiangping , Zhang Xuewei , Yang Ming , Xia Zhenkun , Liu Chi 
Published: June 2024

AbstractBackground and PurposeAirway epithelial cells (AECs) regulate the activation of epithelial–mesenchymal trophic units (EMTUs) during airway remodelling through secretion of signalling mediators. However, the major trigger and the intrinsic pathogenesis of airway remodelling is still obscure.Experimental ApproachThe differing expressed genes in airway epithelia related to airway remodelling were screened and verified by RNA‐sequencing and signalling pathway analysis. Then, the effects of increased cathepsin K (CTSK) in airway epithelia on airway remodelling and EMTU activation were identified both in vitro and in vivo, and the molecular mechanism was elucidated in the EMTU model. The potential of CTSK as an an effective biomarker of airway remodelling was analysed in an asthma cohort of differing severity. Finally, an inhibitor of CTSK was administered for potential therapeutic intervention for airway remodelling in asthma.Key ResultsThe expression of CTSK in airway epithelia increased significantly along with the development of airway remodelling in a house dust mite (HDM)‐stressed asthma model. Increased secretion of CTSK from airway epithelia induced the activation of EMTUs by activation of the PAR2‐mediated pathway. Blockade of CTSK inhibited EMTU activation and alleviated airway remodelling as an effective intervention target of airway remodelling.Conclusion and ImplicationsIncreased expression of CTSK in airway epithelia is involved in the development of airway remodelling in asthma through EMTU activation, mediated partly through the PAR2‐mediated signalling pathway. CTSK is a potential biomarker for airway remodelling, and may also be a useful intervention target for airway remodelling in asthma patients.
Umfassende Analyse des Einflusses der Body Composition auf die Wirksamkeit und das Nebenwirkungsprofil einer Systemtherapie mit Tyrosinkinaseinhibitoren bei Melanompatienten
Authors: Mengoni Miriam , Braun Andreas Dominik , Hinnerichs Mattes Simon , Aghayev Anar , Tüting Thomas , Surov Alexey 
Published: June 2024

ZusammenfassungHintergrundDie Einführung von Tyrosinkinaseinhibitoren (TKI) hat die Behandlung von Patienten mit metastasiertem Melanom erheblich verbessert. Aktuelle Studien haben einen Zusammenhang zwischen dem Body‐Mass‐Index (BMI) und dem klinischen Verlauf von Patienten mit metastasiertem Melanom gezeigt. Weitere Studien mit kontroversen Ergebnissen haben jedoch die Interpretation dieser Ergebnisse erschwert. In der aktuellen Arbeit haben wir Parameter der Körperzusammensetzung (Body Composition) von Melanompatienten, die mit TKI behandelt wurden, analysiert, um deren Stellenwert als Biomarker zu evaluieren.Patienten und MethodikIn einer retrospektiven Kohorte bestehend aus 57 Patienten wurden Parameter der Body Composition anhand von CT‐Scans untersucht und deren Einfluss auf das Therapieansprechen und das Auftreten unerwünschter Ereignisse analysiert. Die Studienkohorte umfasste alle Patienten mit metastasiertem, nicht resektablem Melanom im Stadium III/IV, die in unserer Abteilung eine Erstlinientherapie mit TKI erhalten hatten.ErgebnisseMittels uni‐ und multivariater Analysen stellten wir einen Zusammenhang zwischen dem Gauge‐Index des viszeralen Fettgewebes (VATGI) und dem Überleben fest. Darüber hinaus untersuchten wir weitere Parameter der Body Composition, darunter die Sarkopenie, die ebenfalls mit einem kürzeren Gesamtüberleben assoziiert war. Weiterhin konnten wir nachweisen, dass Patienten mit niedrigem VATGI anteilsweise häufiger eine Fatigue aufwiesen.SchlussfolgerungenUnsere Studie ist die erste explorative Studie, die Parameter der Body Composition als Biomarker für Melanompatienten, die mit TKI behandelt werden, untersucht. Unsere Daten deuten darauf hin, dass der VATGI als Biomarker zur Vorhersage des Therapieerfolges verwendet werden könnte.
Repräsentation von Hautkarzinomen im öffentlichen Bewusstsein – Aufmerksamkeit weltweit und in Deutschland
Authors: Meinzenbach Anne , Kaatz Martin , Springer Steffen , Zieger Michael 
Published: June 2024

ZusammenfassungHintergrund und ZielsetzungIn den letzten Jahren ist eine Zunahme von Hauttumoren zu verzeichnen. Ziel dieser Studie war es daher, die Repräsentation von Hautkrebs im öffentlichen Bewusstsein weltweit und in Deutschland zu untersuchen und festzustellen, ob der Skin Cancer Awareness Month in den Suchinteressen der internetnutzenden Bevölkerung in gleicher Weise wie der Breast Cancer Awareness Month weltweit repräsentiert ist.Daten und MethodikIn dieser Studie wurden die Daten von Google Trends verwendet, um den Grad der öffentlichen Aufmerksamkeit für verschiedene Tumorentitäten und Hautkrebsarten weltweit und in Deutschland zu ermitteln.ErgebnisseDie Ergebnisse dieser Analyse zeigten deutlich ein hohes Niveau für das relative öffentliche Suchinteresse am Thema Brustkrebs weltweit im Sensibilisierungsmonat Oktober. Weltweit und in Deutschland war ein gewisser Anstieg des Suchinteresses beziehungsweise ein gewisser saisonaler Effekt um den Sensibilisierungsmonat Mai für Hautkrebs festzustellen. So zeigte die Analyse beispielsweise ein Suchinteresse im Mai und während der Sommermonate in Deutschland.SchlussfolgerungenEs ist wahrscheinlich, dass die Bevölkerung, zum Beispiel in Deutschland, weiterhin von einer noch stärkeren Betonung des Themas Hautkrebs profitieren könnte.
Diagnoseverzögerung bei Hidradenitis suppurativa untersucht mit Daten von sozialen Medien und gesetzlichen Krankenversicherungen
Authors: Kirschner Uwe , Kahn Maria , Papukchieva Steffeni , Stosio Karolina , Keis Andreas , Biermann Mona H. C. , Häusser‐Fruh Gisela , Sturm Lisa , Eberl Markus , Friedrich Benjamin , Kurzen Hjalmar 
Published: June 2024

ZusammenfassungHintergrundDie chronisch‐entzündliche Hauterkrankung Hidradenitis suppurativa (HS) führt bei Betroffenen zu ausgeprägten Schmerzen und verminderter Lebensqualität. Trotzdem vergehen oft mehrere Jahre bis zur korrekten Diagnosestellung. In dieser Analyse sollten krankheitsbedingte Erfahrungen und Wege der Patienten mit HS untersucht und der ärztlichen Sicht gegenübergestellt werden.Patienten und MethodikFür die Studie wurden Ergebnisse einer Befragung von Dermatologen und deren Patienten zur Versorgungsrealität bei HS in Deutschland sowie öffentliche Beiträge auf Internet‐Foren und in sozialen Medien analysiert. Zusätzlich wurden Abrechnungsdaten deutscher Krankenkassen ausgewertet.ErgebnissePatienten mit HS haben eine um 43,3% reduzierte Arbeitsfähigkeit. Die Dermatologie (26,5%) war der am häufigsten konsultierte Fachbereich, die Diagnose HS wurde dabei überwiegend im stationären Bereich (43,8%) gestellt. Als häufigste alternative Diagnose bei HS‐Patienten wurden Abszesse angegeben (53,2%). Die Analyse von Wechseln zu anderen Behandlern ergab, dass diese in der Dermatologie (34,1%) und der Chirurgie (42,4%) vorwiegend innerhalb des Fachbereiches erfolgen. Überweisungen erhielt die Dermatologie mehrheitlich aus dem hausärztlichen Bereich (67,1%) allerdings nur 12,1% von Chirurgen.SchlussfolgerungenDie Diagnoseverzögerung und die dadurch verlängerte Krankheitsbelastung von Patienten mit HS muss dringend reduziert werden. Dazu sollte, möglichst schon als Teil des Medizinstudiums, ein über die Dermatologie hinaus reichendes Bewusstsein für die Erkrankung, ihre Erkennung und Behandlung gefördert werden.
Decoding changes in tumor‐infiltrating leukocytes through dynamic experimental models and single‐cell technologies
Authors: Lee Colin YC , Clatworthy Menna R , Withers David R 
Published: June 2024

AbstractThe ability to characterize immune cells and explore the molecular interactions that govern their functions has never been greater, fueled in recent years by the revolutionary advance of single‐cell analysis platforms. However, precisely how immune cells respond to different stimuli and where differentiation processes and effector functions operate remain incompletely understood. Inferring cellular fate within single‐cell transcriptomic analyses is now omnipresent, despite the assumptions typically required in such analyses. Recently developed experimental models support dynamic analyses of the immune response, providing insights into the temporal changes that occur within cells and the tissues in which such transitions occur. Here we will review these approaches and discuss how these can be combined with single‐cell technologies to develop a deeper understanding of the immune responses that should support the development of better therapeutic options for patients.
Enhancing Surgical Robotics: A Dynamic Model and Optimized Control Strategy for Cable-Driven Continuum Robots
Authors: Ghoul A. , Djeffal S. , Wang H. , Kara K. , Hadjili M. L. 
Published: June 2024

Abstract
This paper tackles the challenges encountered in surgical continuum robotics by introducing a dynamic model tailored for a cable-driven continuum robot. The intricacies of dynamic modeling and control frequently lead to suboptimal outcomes. Prior studies have often lacked comprehensive descriptions of individual robot component movements, thereby impeding control processes, especially in the presence of external disturbances. Although machine learning-based models show promise across different domains, they face hurdles in continuum robotics due to the complexity of the systems involved. Traditional mathematical models, in contrast, offer explicit equations, providing better interpretability, unlike machine learning models that may struggle with generalization, especially in highly nonlinear systems like continuum robots. The developed model adeptly captures the kinematic and dynamic constraints of various robot segments, serving as the foundation for a robust optimized control strategy. This strategy, which integrates computed torque control and particle swarm optimization, enables real-time computation of joint torques based on feedback, ensuring precise and stable task execution even amidst external perturbations. Comparative analysis with an optimized proportional-integral-derivative controller unequivocally demonstrates the superiority of the optimized computed torque controller in settling time, overshoot, and robustness against disturbances. This advancement represents a noteworthy contribution to robotics, with the potential to significantly enhance continuum robot performance in surgical and inspection applications, thereby fostering innovative advancements across various fields.
Uncertainty components in profile likelihood fits
Authors: Pinto Andrés , Wu Zhibo , Balli Fabrice , Berger Nicolas , Boonekamp Maarten , Chapon Émilien , Kawamoto Tatsuo , Malaescu Bogdan 
Published: June 2024

AbstractWhen a measurement of a physical quantity is reported, the total uncertainty is usually decomposed into statistical and systematic uncertainties. This decomposition is not only useful for understanding the contributions to the total uncertainty, but is also required to propagate these contributions in subsequent analyses, such as combinations or interpretation fits including results from other measurements or experiments. In profile likelihood fits, widely applied in high-energy physics analyses, contributions of systematic uncertainties are routinely quantified using “impacts,” which are not adequate for such applications. We discuss the difference between impacts and actual uncertainty components, and establish methods to determine the latter in a wide range of statistical models.
Self-similar collapse in Painlevé–Gullstrand coordinates
Authors: Chakrabarti Soumya , Singha Chiranjeeb 
Published: June 2024

AbstractWe report a family of self-similar exact solutions in General Relativity. The solutions are found in a Painleve-Gullstrand coordinate system but can also be transformed smoothly into a diagonal form. The solutions represent a gravitational collapse leading to three possible outcomes, depending on the parameter space: (i) a collapse followed by a bounce and dispersal of the clustered matter distribution, (ii) a rapid collapse followed by a bounce and an eventual re-collapse, and (iii) a standard collapse leading to zero proper volume. Profiles of the energy conditions are studied for all of the scenarios, and it is noted that a bounce is usually associated with a violation of the Null Energy Condition. It is found that more than one null surfaces (apparent horizons) can develop during the collapse. We also discuss that for a general metric tensor having a conformal symmetry, some regions of the parameter space allows a formation of null throat, much like a wormhole. Matching the metric with a Schwarzschild metric in Painleve–Gullstrand form leads to the geodesic equation for a zero energy falling particle in the exterior.
Abstract A003: Unwinding the complexities of helicases as compelling drug targets in oncology
Authors: Mamane Yael , Caple Zoe , Chapman Katie , Henderson Ian , Jordan Allan , Lyne Vanessa , Okoye Cynthia , Rigoreau Laurent , Kadamur Ganesh , Thomson Stuart , Tomlinson Chris , Wolf Jana 
Published: June 2024

Abstract
In recent years, helicases have moved to the forefront of research as novel drug targets for a variety of human diseases, including cancer. As critical components of the cell cycle and DNA repair, these enzymes offer an attractive point of therapeutic intervention. Recent bioinformatic endeavours such as the Cancer DepMap have further highlighted the essentiality of these proteins in the progression of numerous cancers. Inhibitors of Werner helicase (WRN) entered Phase I evaluation in 2023, after studies highlighted its role in tumours with microsatellite instability (MSI) and impaired mismatch repair (MMR). Building on these advances, helicases now represent a significant drug target class and are the subject of intense research. However, these targets present significant complexities in their prosecution. Hit finding and robust validation of these putative active compounds remains challenging, with high attrition rates and significant sensitivity to false positives. Resultant hits require thorough biological characterisation via both biochemical and biophysical methods, alongside determination of selectivity against other closely related family members, to increase confidence in their provenance before commencing a detailed drug discovery project. To exemplify these approaches, we have profiled three commercially available WRN inhibitors from two chemical series through a selection of biochemical and biophysical assays. The three compounds exhibit excellent selectivity against 6 distinct helicase/translocase targets. In Michaelis-Menten mechanism of Inhibition studies, we defined contrasting mechanisms of inhibition for the two series and were also able to identify time dependent inhibition with one compound series. Analysing binding interactions of the compounds against protein and protein:substrate complexes, via a fluorescent thermal shift assay (FTSA) and microscale thermophoresis (MST), enabled us to further understand and interrogate the mechanism of inhibition. Herein, we describe some of our experiences, learnings and best practices when prosecuting these compelling, but challenging, targets.
Citation Format: Yael Mamane, Zoe Caple, Katie Chapman, Ian Henderson, Allan Jordan, Vanessa Lyne, Cynthia Okoye, Laurent Rigoreau, Ganesh Kadamur, Stuart Thomson, Chris Tomlinson, Jana Wolf. Unwinding the complexities of helicases as compelling drug targets in oncology [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities; 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr A003.
Abstract B001: Cytidine diphosphate diacylglycerol synthase 2 is a synthetic lethal target in mesenchymal cancers
Authors: Arnoldus Tim , van Vliet Alex , de Groot Adriaan F.H. , Blomberg Niek , Bleijerveld Onno B. , van Hal-van Veen Susan E. , Grootemaat Anita E. , Harkes Rolf , van der Wel Nicole N. , Altelaar Maarten , Giera Martin , Peeper Daniel S. 
Published: June 2024

Abstract
This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR009) of the Conference Program/Proceedings.
Citation Format: Tim Arnoldus, Alex van Vliet, Adriaan F.H. de Groot, Niek Blomberg, Onno B. Bleijerveld, Susan E. van Hal-van Veen, Anita E. Grootemaat, Rolf Harkes, Nicole N. van der Wel, Maarten Altelaar, Martin Giera, Daniel S. Peeper. Cytidine diphosphate diacylglycerol synthase 2 is a synthetic lethal target in mesenchymal cancers [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities; 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr B001.
Abstract B007: Unexpected synthetic lethality mechanisms in eIF4A-targeted therapy
Authors: Zhao Na , Kabotyanski Elena , Saltzman Alexander , Rosen Jeffrey 
Published: June 2024

Abstract
BACKGROUND Dysregulation of mRNA translation, which is prevalent in cancer, presents an underexplored therapeutic vulnerability. The eukaryotic translation initiation factor 4A (eIF4A) promotes protein synthesis by unwinding secondary structures in the 5’-untranslated region of mRNAs to facilitate translation initiation. While perturbation of eIF4A minimally affects the health normal cells, it is crucial for the translation of many oncogenes and is considered essential in most cancer cell lines. Zotatifin, a first-in-class eIF4A inhibitor, is currently under evaluation in a Phase I/II clinical trial for KRAS-mutant tumors and ER+ breast cancers. In addition to the tumor-intrinsic effect, our recent publication in the Journal of Clinical Investigation revealed that pharmacological targeting of eIF4A not only affects tumor cells but also improves the tumor immune microenvironment. This results in tumor inhibition, heightened sensitivity to immune checkpoint blockade, and remarkable synergism with platinum in various preclinical triple-negative breast cancer mouse models. OBJECTIVES To investigate the mechanism underlying the synergy between eIF4A-targeted therapy and platinum. UNPUBLISHED RESULT Mass spectrometry proteomic analysis coupled with ELISA and qPCR analysis unveiled that eIF4A-targeted therapy promotes type I interferon (IFN) secretion and induces a robust type I IFN response both in vivo and in vitro. This suggests a tumor cell-autonomous effect of IFN induction by eIF4A inhibition. Combining platinum with eIF4A-targeted therapy further heightens the type I IFN response in vivo, leading to T cell-and macrophage-dependent synergistic tumor regression. Interestingly, this synergy was not observed in vitro, indicating the involvement of the host immune system in the efficacy of combination therapy. It is possible that platinum may stimulate certain immune populations to secrete IFN, which acts on tumor cells to upregulate their IFN response. CONCLUSION Activation of the type I IFN response by eIF4A inhibition combined with platinum in vivo can lead to synthetic lethality of tumor cells. These studies not only offer novel insights into eIF4A biology but also provide valuable guidance for ongoing and future clinical trials.
Citation Format: Na Zhao, Elena Kabotyanski, Alexander Saltzman, Jeffrey Rosen. Unexpected synthetic lethality mechanisms in eIF4A-targeted therapy [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities; 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr B007.