11,461 results on '"Pantel A"'
Search Results
2. Next-generation phenotyping integrated in a national framework for patients with ultrarare disorders improves genetic diagnostics and yields new molecular findings
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Schmidt, Axel, Danyel, Magdalena, Grundmann, Kathrin, Brunet, Theresa, Klinkhammer, Hannah, Hsieh, Tzung-Chien, Engels, Hartmut, Peters, Sophia, Knaus, Alexej, Moosa, Shahida, Averdunk, Luisa, Boschann, Felix, Sczakiel, Henrike Lisa, Schwartzmann, Sarina, Mensah, Martin Atta, Pantel, Jean Tori, Holtgrewe, Manuel, Bösch, Annemarie, Weiß, Claudia, Weinhold, Natalie, Suter, Aude-Annick, Stoltenburg, Corinna, Neugebauer, Julia, Kallinich, Tillmann, Kaindl, Angela M., Holzhauer, Susanne, Bührer, Christoph, Bufler, Philip, Kornak, Uwe, Ott, Claus-Eric, Schülke, Markus, Nguyen, Hoa Huu Phuc, Hoffjan, Sabine, Grasemann, Corinna, Rothoeft, Tobias, Brinkmann, Folke, Matar, Nora, Sivalingam, Sugirthan, Perne, Claudia, Mangold, Elisabeth, Kreiss, Martina, Cremer, Kirsten, Betz, Regina C., Mücke, Martin, Grigull, Lorenz, Klockgether, Thomas, Spier, Isabel, Heimbach, André, Bender, Tim, Brand, Fabian, Stieber, Christiane, Morawiec, Alexandra Marzena, Karakostas, Pantelis, Schäfer, Valentin S., Bernsen, Sarah, Weydt, Patrick, Castro-Gomez, Sergio, Aziz, Ahmad, Grobe-Einsler, Marcus, Kimmich, Okka, Kobeleva, Xenia, Önder, Demet, Lesmann, Hellen, Kumar, Sheetal, Tacik, Pawel, Basin, Meghna Ahuja, Incardona, Pietro, Lee-Kirsch, Min Ae, Berner, Reinhard, Schuetz, Catharina, Körholz, Julia, Kretschmer, Tanita, Di Donato, Nataliya, Schröck, Evelin, Heinen, André, Reuner, Ulrike, Hanßke, Amalia-Mihaela, Kaiser, Frank J., Manka, Eva, Munteanu, Martin, Kuechler, Alma, Cordula, Kiewert, Hirtz, Raphael, Schlapakow, Elena, Schlein, Christian, Lisfeld, Jasmin, Kubisch, Christian, Herget, Theresia, Hempel, Maja, Weiler-Normann, Christina, Ullrich, Kurt, Schramm, Christoph, Rudolph, Cornelia, Rillig, Franziska, Groffmann, Maximilian, Muntau, Ania, Tibelius, Alexandra, Schwaibold, Eva M. C., Schaaf, Christian P., Zawada, Michal, Kaufmann, Lilian, Hinderhofer, Katrin, Okun, Pamela M., Kotzaeridou, Urania, Hoffmann, Georg F., Choukair, Daniela, Bettendorf, Markus, Spielmann, Malte, Ripke, Annekatrin, Pauly, Martje, Münchau, Alexander, Lohmann, Katja, Hüning, Irina, Hanker, Britta, Bäumer, Tobias, Herzog, Rebecca, Hellenbroich, Yorck, Westphal, Dominik S., Strom, Tim, Kovacs, Reka, Riedhammer, Korbinian M., Mayerhanser, Katharina, Graf, Elisabeth, Brugger, Melanie, Hoefele, Julia, Oexle, Konrad, Mirza-Schreiber, Nazanin, Berutti, Riccardo, Schatz, Ulrich, Krenn, Martin, Makowski, Christine, Weigand, Heike, Schröder, Sebastian, Rohlfs, Meino, Vill, Katharina, Hauck, Fabian, Borggraefe, Ingo, Müller-Felber, Wolfgang, Kurth, Ingo, Elbracht, Miriam, Knopp, Cordula, Begemann, Matthias, Kraft, Florian, Lemke, Johannes R., Hentschel, Julia, Platzer, Konrad, Strehlow, Vincent, Abou Jamra, Rami, Kehrer, Martin, Demidov, German, Beck-Wödl, Stefanie, Graessner, Holm, Sturm, Marc, Zeltner, Lena, Schöls, Ludger J., Magg, Janine, Bevot, Andrea, Kehrer, Christiane, Kaiser, Nadja, Turro, Ernest, Horn, Denise, Grüters-Kieslich, Annette, Klein, Christoph, Mundlos, Stefan, Nöthen, Markus, Riess, Olaf, Meitinger, Thomas, Krude, Heiko, Krawitz, Peter M., Haack, Tobias, Ehmke, Nadja, and Wagner, Matias
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- 2024
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3. Clinical applications of circulating tumor cells in patients with solid tumors
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Smit, Daniel J., Schneegans, Svenja, and Pantel, Klaus
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- 2024
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4. Mutation analysis in individual circulating tumor cells depicts intratumor heterogeneity in melanoma
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Sementsov, Mark, Ott, Leonie, Kött, Julian, Sartori, Alexander, Lusque, Amelie, Degenhardt, Sarah, Segier, Bertille, Heidrich, Isabel, Volkmer, Beate, Greinert, Rüdiger, Mohr, Peter, Simon, Ronald, Stadler, Julia-Christina, Irwin, Darryl, Koch, Claudia, Andreas, Antje, Deitert, Benjamin, Thewes, Verena, Trumpp, Andreas, Schneeweiss, Andreas, Belloum, Yassine, Peine, Sven, Wikman, Harriett, Riethdorf, Sabine, Schneider, Stefan W, Gebhardt, Christoffer, Pantel, Klaus, and Keller, Laura
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- 2024
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5. Cochlear implant therapy improves the quality of life and social participation in the elderly: a prospective long-term evaluation
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Issing, Christian, Loth, Andreas G., Sakmen, Kenan D., Guchlerner, Leon, Helbig, Silke, Baumann, Uwe, Pantel, Johannes, and Stöver, Timo
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- 2024
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6. First molecular characterization of related cases of healthcare-associated infections involving multidrug-resistant Enterococcus faecium vanA in Algeria
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Benammar S, Pantel A, Aujoulat F, Benmehidi M, Courcol R, Lavigne JP, Romano-Bertrand S, and Marchandin H
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outbreak ,genotyping ,MLST ,rep-PCR ,PFGE ,molecular epidemiology. ,Infectious and parasitic diseases ,RC109-216 - Abstract
Sonia Benammar,1,2 Alix Pantel,3,4 Fabien Aujoulat,5 Messaoud Benmehidi,1,2 René Courcol,6,7 Jean-Philippe Lavigne,3,4 Sara Romano-Bertrand,5,8 Hélène Marchandin3,5 1Department of Microbiology, University Hospital Center Touhami Benflis, Batna, Algeria; 2Department of Medicine, University Batna 2, Batna, Algeria; 3Department of Microbiology, Nîmes University Hospital, Nîmes, France; 4Faculty of Medicine, National Institute of Health and Medical Research, INSERM U1047, University of Montpellier, Nîmes, France; 5HydroSciences Montpellier, CNRS, IRD, University of Montpellier, University Hospital of Montpellier-Nîmes, Montpellier, France; 6Faculty of Medicine, University of Lille, Lille, France; 7Department of Bacteriology, Institute of Microbiology, Lille University Hospital, Lille, France; 8Department of Infection Control, Montpellier University Hospital, Montpellier, France Purpose: Vancomycin-resistant Enterococcus (VRE) faecium (VREfm) are highly resistant bacteria emerging worldwide and rarely studied using molecular tools in Algeria since their first report in 2006. The aim of the study was to investigate healthcare-associated infections (HAIs) involving the first VRE in Batna University Hospital, Algeria, and characterize isolates using molecular tools.Patients and methods: Medical charts were reviewed for patients with VREfm. van genes were detected by multiplex polymerase chain reaction (PCR), and strains were characterized by automated repetitive sequence-based PCR (rep-PCR), multiplex rep-PCR, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST).Results: During a 6-month period, VREfm infections occurred in four patients hospitalized in three wards. The four isolates were E. faecium vanA belonging to the hospital-adapted clonal complex 17. PCR-based methods did not discriminate the isolates but MLST and PFGE delineated a subgroup of three VREfm of identical pulsotype and sequence type (ST) 80 (yet identified for five isolates in the international PubMLST database) while the fourth isolate was of ST789 (not previously identified for a VREfm) and displayed an unrelated pulsotype. The three genotypically related isolates were recovered in patients who underwent surgery in the same department, suggesting an outbreak for which the source and route of transmission remained unidentified.Conclusion: This first molecular epidemiology study of VRE in Algeria was useful in delimiting an outbreak involving three of the four HAI cases and revealed rarely encountered genotypes. Considering the threat and burden of VRE infections worldwide, particularly in the USA, and the late emergence in Algeria, our study supports the urgent need for improved and early adequate infection control measures to avoid VRE spread in North African hospitals. Keywords: outbreak, genotyping, MLST, rep-PCR, PFGE, molecular epidemiology
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- 2018
7. Zebra finches increase social behavior in traffic noise: Implications for urban songbirds
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Hawkins, Carly E, Pantel, Jelena H, Palia, Sophia T, Folks, Christine C, and Swaddle, John P
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Zoology ,Ecology ,Biological Sciences ,Life on Land ,Noise pollution ,Disturbance ,Songbirds ,Spatial behavior ,Social behavior ,Behavioral Science & Comparative Psychology - Abstract
Abstract: Traffic noise is a pervasive pollutant that affects wildlife at individual and group levels through mechanisms such as disrupting communication, affecting antipredator strategy, and/or changing how they use space within a habitat. Urbanization is expanding rapidly—few places remain untouched by anthropogenic noise disturbance—so understanding the implications of noise on wildlife behavior is paramount to conservation efforts. We asked whether traffic noise could change space use and social network metrics in flocks of captive birds. Specifically, we quantified the effects of playbacks of traffic noise on individual sociality (weighted degree, number of social partners weighted by the frequency of interactions with those social partners) and flock clustering (global clustering coefficient, connectivity of neighbors). In this study, we recorded social interactions and space use of flocks of captive zebra finches (Taeniopygia guttata) before, during, and after an experimental traffic noise introduction in two treatments: high- and lower-amplitude noise. Our results demonstrated that individual sociality and flock clustering increased in response to the noise introduction in both high-amplitude and low-amplitude treatments. Additionally, birds in the high-amplitude treatment spent more time in the room with active playback during noise playback whereas birds in the lower-amplitude treatment decreased time spent in the room closest to the high-amplitude treatment. Increased social behavior in response to traffic noise could influence disease transmission, social learning, and mating dynamics. We suggest future studies explore the mechanisms driving increased social behavior in traffic noise, such as perceived predation risk, vigilance, and cross-sensory interference.
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- 2024
8. Prävention und Gesundheitsförderung im und für das Alter stärken
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Gellert, Paul, Brandenburg, Hermann, Franke, Annette, Kessler, Eva-Marie, Krupp, Sonja, Pantel, Johannes, Schramek, Renate, Simm, Andreas, Swoboda, Walter, Wurm, Susanne, and Fuellen, Georg
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- 2024
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9. Total-body PET/CT or LAFOV PET/CT? Axial field-of-view clinical classification
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Mingels, Clemens, Caobelli, Federico, Alavi, Abass, Sachpekidis, Christos, Wang, Meiyun, Nalbant, Hande, Pantel, Austin R, Shi, Hongcheng, Rominger, Axel, and Nardo, Lorenzo
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Biomedical and Clinical Sciences ,Clinical Sciences ,Other Physical Sciences ,Nuclear Medicine & Medical Imaging ,Clinical sciences - Published
- 2023
10. Multibiomarker panels in liquid biopsy for early detection of pancreatic cancer – a comprehensive review
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Kim-Lea Reese, Klaus Pantel, and Daniel J. Smit
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Blood-based biomarkers ,Early-stage diagnosis ,Liquid biopsy ,Multimarker panel ,Pancreatic cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Pancreatic ductal adenocarcinoma (PDAC) is frequently detected in late stages, which leads to limited therapeutic options and a dismal overall survival rate. To date, no robust method for the detection of early-stage PDAC that can be used for targeted screening approaches is available. Liquid biopsy allows the minimally invasive collection of body fluids (typically peripheral blood) and the subsequent analysis of circulating tumor cells or tumor-associated molecules such as nucleic acids, proteins, or metabolites that may be useful for the early diagnosis of PDAC. Single biomarkers may lack sensitivity and/or specificity to reliably detect PDAC, while combinations of these circulating biomarkers in multimarker panels may improve the sensitivity and specificity of blood test-based diagnosis. In this narrative review, we present an overview of different liquid biopsy biomarkers for the early diagnosis of PDAC and discuss the validity of multimarker panels.
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- 2024
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11. Commercially available tests for determining cefiderocol susceptibility display variable performance in the Achromobacter genus
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Vincent Jean-Pierre, Pauline Sorlin, Katy Jeannot, Raphaël Chiron, Jean-Philippe Lavigne, Alix Pantel, and Hélène Marchandin
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Cefiderocol ,Achromobacter ,Susceptibility testing ,Microdilution ,Disk ,Diffusion ,Therapeutics. Pharmacology ,RM1-950 ,Infectious and parasitic diseases ,RC109-216 ,Microbiology ,QR1-502 - Abstract
Abstract Background Cefiderocol is a siderophore-conjugated cephalosporin increasingly used in the management of Achromobacter infections. Testing for cefiderocol susceptibility is challenging with distinct recommendations depending on the pathogens. Objectives We evaluated the performance of commercial tests for testing cefiderocol susceptibility in the Achromobacter genus and reviewed the literature. Methods Diffusion (disks, MIC gradient test strips [MTS], Liofilchem) and broth microdilution (BMD) methods (ComASP™, Liofilchem; UMIC®, Bruker) were compared with the BMD reference method according to the EUCAST guidelines on 143 Achromobacter strains from 14 species with MIC50/90 of ≤ 0.015/0.5 mg/L. A literature search was conducted regardless of method or species. Results None of the methods tested fulfilled an acceptable essential agreement (EA). MTS displayed the lowest EA (30.8%) after UMIC® (49%) and ComASP™ (76.9%). All methods achieved an acceptable bias, with MICs either underestimated using MTS (-1.3%) and ComASP™ (-14.2%) or overestimated with UMIC® (+ 9.1%). Inhibition zone diameters ranged from 6 to 38 mm (IZD50/90=33/30 mm). UMIC® and ComASP™ failed to categorize one or the two cefiderocol-resistant strains of this study as resistant unlike the diffusion-based methods. The literature review highlighted distinct performance of the available methods according to pathogens and testing conditions. Conclusions The use of MTS is discouraged for Achromobacter spp. Disk diffusion can be used to screen for susceptible strains by setting a threshold diameter of 30 mm. UMIC® and ComASP™ should not be used as the sole method but have to be systematically associated with disk diffusion to detect the yet rarely described cefiderocol-resistant Achromobacter sp. strains.
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- 2024
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12. Nutrition guidance within a multimodal intervention improves diet quality in prodromal Alzheimer’s disease: Multimodal Preventive Trial for Alzheimer’s Disease (MIND-ADmini)
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Nicholas Levak, Jenni Lehtisalo, Charlotta Thunborg, Eric Westman, Pia Andersen, Sandrine Andrieu, Laus M. Broersen, Nicola Coley, Tobias Hartmann, Gerd Faxén Irving, Francesca Mangialasche, Tiia Ngandu, Johannes Pantel, Anna Rosenberg, Shireen Sindi, Hilkka Soininen, Alina Solomon, Rui Wang, and Miia Kivipelto
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Nutrition ,Alzheimer’s disease ,Dementia ,Multimodal trial ,Lifestyle ,Prodromal Alzheimer’s disease ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background Multimodal lifestyle interventions can benefit overall health, including cognition, in populations at-risk for dementia. However, little is known about the effect of lifestyle interventions in patients with prodromal Alzheimer’s disease (AD). Even less is known about dietary intake and adherence to dietary recommendations within this population making it difficult to design tailored interventions for them. Method A 6-month MIND-ADmini pilot randomized controlled trial (RCT) was conducted among 93 participants with prodromal AD in Sweden, Finland, Germany, and France. Three arms were included in the RCT: 1) multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management, and social stimulation); 2) multimodal lifestyle intervention + medical food product; and 3) regular health advice (control group). Adherence to dietary advice was assessed with a brief food intake questionnaire by using the Healthy Diet Index (HDI) and Mediterranean Diet Adherence Screener (MEDAS). The intake of macro- and micronutrients were analyzed on a subsample using 3-day food records. Results The dietary quality in the intervention groups, pooled together, improved compared to that of the control group at the end of the study, as measured with by HDI (p = 0.026) and MEDAS (p = 0.008). The lifestyle-only group improved significantly more in MEDAS (p = 0.046) and almost significantly in HDI (p = 0.052) compared to the control group, while the lifestyle + medical food group improved in both HDI (p = 0.042) and MEDAS (p = 0.007) during the study. There were no changes in macro- or micronutrient intake for the intervention groups at follow-up; however, the intakes in the control group declined in several vitamins and minerals when adjusted for energy intake. Conclusion These results suggest that dietary intervention as part of multimodal lifestyle interventions is feasible and results in improved dietary quality in a population with prodromal AD. Nutrient intakes remained unchanged in the intervention groups while the control group showed a decreasing nutrient density. Trial registration ClinicalTrials.gov NCT03249688, 2017–07-08.
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- 2024
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13. Stability and Fluctuations in Complex Ecological Systems
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Forgoston, Eric, Day, Sarah, de Ruiter, Peter C., Doelman, Arjen, Hartemink, Nienke, Hastings, Alan, Hemerik, Lia, Hening, Alexandru, Hofbauer, Josef, Kefi, Sonia, Kessler, David A., Klauschies, Toni, Kuehn, Christian, Li, Xiaoxiao, Moore, John C., Morrien, Elly, Neutel, Anje-Margriet, Pantel, Jelena, Schreiber, Sebastian J., Shaw, Leah B., Shnerb, Nadav, Siero, Eric, Storch, Laura S., Thorne, Michael A. S., van de Leemput, Ingrid, van Velzen, Ellen, and Weinans, Els
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Quantitative Biology - Populations and Evolution - Abstract
From 08-12 August, 2022, 32 individuals participated in a workshop, Stability and Fluctuations in Complex Ecological Systems, at the Lorentz Center, located in Leiden, The Netherlands. An interdisciplinary dialogue between ecologists, mathematicians, and physicists provided a foundation of important problems to consider over the next 5-10 years. This paper outlines eight areas including (1) improving our understanding of the effect of scale, both temporal and spatial, for both deterministic and stochastic problems; (2) clarifying the different terminologies and definitions used in different scientific fields; (3) developing a comprehensive set of data analysis techniques arising from different fields but which can be used together to improve our understanding of existing data sets; (4) having theoreticians/computational scientists collaborate closely with empirical ecologists to determine what new data should be collected; (5) improving our knowledge of how to protect and/or restore ecosystems; (6) incorporating socio-economic effects into models of ecosystems; (7) improving our understanding of the role of deterministic and stochastic fluctuations; (8) studying the current state of biodiversity at the functional level, taxa level and genome level., Comment: 22 pages
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- 2023
14. Intermediate and long-term exposure to air pollution and temperature and the extracellular microRNA profile of participants in the normative aging study (NAS)
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Danesh Yazdi, Mahdieh, Nassan, Feiby L, Kosheleva, Anna, Wang, Cuicui, Xu, Zongli, Di, Qian, Requia, Weeberb J, Comfort, Nicole T, Wu, Haotian, Laurent, Louise C, DeHoff, Peter, Vokonas, Pantel, Baccarelli, Andrea A, and Schwartz, Joel D
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Environmental Sciences ,Pollution and Contamination ,Aging ,Genetics ,Biotechnology ,Climate-Related Exposures and Conditions ,Aetiology ,2.2 Factors relating to the physical environment ,Good Health and Well Being ,Humans ,Air Pollutants ,Nitrogen Dioxide ,Temperature ,Particulate Matter ,Air Pollution ,MicroRNAs ,Environmental Exposure ,Ozone ,Particulate matter ,Nitrogen dioxide ,Ambient temperature ,microRNA ,Air pollution ,Chemical Sciences ,Biological Sciences ,Toxicology ,Biological sciences ,Chemical sciences ,Environmental sciences - Abstract
BackgroundThe molecular effects of intermediate and long-term exposure to air pollution and temperature, such as those on extracellular microRNA (ex-miRNA) are not well understood but may have clinical consequences.ObjectivesTo assess the association between exposure to ambient air pollution and temperature and ex-miRNA profiles.MethodsOur study population consisted of 734 participants in the Normative Aging Study (NAS) between 1999 and 2015. We used high-resolution models to estimate four-week, eight-week, twelve-week, six-month, and one-year moving averages of PM2.5, O3, NO2, and ambient temperature based on geo-coded residential addresses. The outcome of interest was the extracellular microRNA (ex-miRNA) profile of each participant over time. We used a longitudinal quantile regression approach to estimate the association between the exposures and each ex-miRNA. Results were corrected for multiple comparisons and ex-miRNAs that were still significantly associated with the exposures were further analyzed using KEGG pathway analysis and Ingenuity Pathway Analysis.ResultsWe found 151 significant associations between levels of PM2.5, O3, NO2, and ambient temperature and 82 unique ex-miRNAs across multiple quantiles. Most of the significant results were associations with intermediate-term exposure to O3, long-term exposure to PM2.5, and both intermediate and long-term exposure to ambient temperature. The exposures were most often associated with the 75th and 90th percentile of the outcomes. Pathway analyses of significant ex-miRNAs revealed their involvement in biological pathways involving cell function and communication as well as clinical diseases such as cardiovascular disease, respiratory disease, and neurological disease.ConclusionOur results show that intermediate and long-term exposure to all our exposures of interest were associated with changes in the ex-miRNA profile of study participants. Further studies on environmental risk factors and ex-miRNAs are warranted.
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- 2023
15. Pembrolizumab-induced vasculitis demonstrated by FDG-PET/CT
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Tuan Vu, BS, Sophia R. O'Brien, MD, Shawn X. Ma, MD, Karthik M. Sundaram, MD, PhD, and Austin R. Pantel, MD, MSTR
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PET imaging ,FDG ,Vasculitis ,Pembrolizumab ,Immune checkpoint inhibitors ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 - Abstract
A 76-year-old man with a history of malignant pleural mesothelioma treated with pembrolizumab underwent FDG-PET/CT for restaging. The images demonstrated FDG uptake overlying the right hepatic and splenic artery, which were new from the previous FDG-PET/CT 2.5 years prior before the patient started pembrolizumab, suspicious for vasculitis. A follow-up MRI supported the diagnosis with evidence of celiac, splenic, common hepatic, and right hepatic artery involvement. Pembrolizumab was discontinued and the patient received a short course of oral glucocorticoids. Subsequent FDG-PET/CT performed 14 months after initiation of treatment for vasculitis demonstrated resolution of vasculitis. Immune checkpoint inhibitors can cause vasculitis, which can be recognized on FDG-PET/CT and lead to appropriate treatment.
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- 2024
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16. Multibiomarker panels in liquid biopsy for early detection of pancreatic cancer – a comprehensive review
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Reese, Kim-Lea, Pantel, Klaus, and Smit, Daniel J.
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- 2024
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17. Commercially available tests for determining cefiderocol susceptibility display variable performance in the Achromobacter genus
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Jean-Pierre, Vincent, Sorlin, Pauline, Jeannot, Katy, Chiron, Raphaël, Lavigne, Jean-Philippe, Pantel, Alix, and Marchandin, Hélène
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- 2024
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18. Nutrition guidance within a multimodal intervention improves diet quality in prodromal Alzheimer’s disease: Multimodal Preventive Trial for Alzheimer’s Disease (MIND-ADmini)
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Levak, Nicholas, Lehtisalo, Jenni, Thunborg, Charlotta, Westman, Eric, Andersen, Pia, Andrieu, Sandrine, Broersen, Laus M., Coley, Nicola, Hartmann, Tobias, Irving, Gerd Faxén, Mangialasche, Francesca, Ngandu, Tiia, Pantel, Johannes, Rosenberg, Anna, Sindi, Shireen, Soininen, Hilkka, Solomon, Alina, Wang, Rui, and Kivipelto, Miia
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- 2024
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19. Master corepressor inactivation through multivalent SLiM-induced polymerization mediated by the oncogene suppressor RAI2
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Goradia, Nishit, Werner, Stefan, Mullapudi, Edukondalu, Greimeier, Sarah, Bergmann, Lina, Lang, Andras, Mertens, Haydyn, Węglarz, Aleksandra, Sander, Simon, Chojnowski, Grzegorz, Wikman, Harriet, Ohlenschläger, Oliver, von Amsberg, Gunhild, Pantel, Klaus, and Wilmanns, Matthias
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- 2024
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20. Cefiderocol susceptibility of Achromobacter spp.: study of an accurately identified collection of 230 strains
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Jean-Pierre, Vincent, Sorlin, Pauline, Pantel, Alix, Chiron, Raphaël, Lavigne, Jean-Philippe, Jeannot, Katy, and Marchandin, Hélène
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- 2024
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21. Integrating a multimodal lifestyle intervention with medical food in prodromal Alzheimer’s disease: the MIND-ADmini randomized controlled trial
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Thunborg, Charlotta, Wang, Rui, Rosenberg, Anna, Sindi, Shireen, Andersen, Pia, Andrieu, Sandrine, Broersen, Laus M., Coley, Nicola, Couderc, Celine, Duval, Celine Z., Faxen-Irving, Gerd, Hagman, Göran, Hallikainen, Merja, Håkansson, Krister, Kekkonen, Eija, Lehtisalo, Jenni, Levak, Nicholas, Mangialasche, Francesca, Pantel, Johannes, Rydström, Anders, Stigsdotter-Neely, Anna, Wimo, Anders, Ngandu, Tiia, Soininen, Hilkka, Hartmann, Tobias, Solomon, Alina, and Kivipelto, Miia
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- 2024
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22. Diagnostic leukapheresis reveals distinct phenotypes of NSCLC circulating tumor cells
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Rieckmann, Lisa-Marie, Spohn, Michael, Ruff, Lisa, Agorku, David, Becker, Lisa, Borchers, Alina, Krause, Jenny, O’Reilly, Roisin, Hille, Jurek, Velthaus-Rusik, Janna-Lisa, Beumer, Niklas, Günther, Armin, Willnow, Lena, Imbusch, Charles D., Iglauer, Peter, Simon, Ronald, Franzenburg, Sören, Winter, Hauke, Thomas, Michael, Bokemeyer, Carsten, Gagliani, Nicola, Krebs, Christian F., Sprick, Martin, Hardt, Olaf, Riethdorf, Sabine, Trumpp, Andreas, Stoecklein, Nikolas H., Peine, Sven, Rosenstiel, Philipp, Pantel, Klaus, Loges, Sonja, and Janning, Melanie
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- 2024
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23. HERC5 downregulation in non-small cell lung cancer is associated with altered energy metabolism and metastasis
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Schneegans, Svenja, Löptien, Jana, Mojzisch, Angelika, Loreth, Desirée, Kretz, Oliver, Raschdorf, Christoph, Hanssen, Annkathrin, Gocke, Antonia, Siebels, Bente, Gunasekaran, Karthikeyan, Ding, Yi, Oliveira-Ferrer, Leticia, Brylka, Laura, Schinke, Thorsten, Schlüter, Hartmut, Paatero, Ilkka, Voß, Hannah, Werner, Stefan, Pantel, Klaus, and Wikman, Harriet
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- 2024
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24. Treating pain in patients with Ehlers–Danlos syndrome: Multidisciplinary management of a multisystemic disease
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Börsch, Natalie, Mücke, Martin, Maier, Andrea, Conrad, Rupert, Pantel, Jean Tori, Sellin, Julia, Mani, Kyros, and Chopra, Pradeep
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- 2024
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25. Kurze Wege zur Diagnose mit künstlicher Intelligenz – systematische Literaturrecherche zu „diagnostic decision support systems“
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Sellin, Julia, Pantel, Jean Tori, Börsch, Natalie, Conrad, Rupert, and Mücke, Martin
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- 2024
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26. Copy number variation analysis in 138 families with steroid-resistant nephrotic syndrome identifies causal homozygous deletions in PLCE1 and NPHS2 in two families
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Pantel, Dalia, Mertens, Nils D., Schneider, Ronen, Hölzel, Selina, Kari, Jameela A., Desoky, Sherif El, Shalaby, Mohamed A., Lim, Tze Y., Sanna-Cherchi, Simone, Shril, Shirlee, and Hildebrandt, Friedhelm
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- 2024
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27. Age-related changes in energy metabolism in peripheral mononuclear blood cells (PBMCs) and the brains of cognitively healthy seniors
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Silaidos, Carmina V., Reutzel, Martina, Wachter, Lena, Dieter, Fabian, Ludin, Nasir, Blum, Werner F., Wudy, Stefan A., Matura, Silke, Pilatus, Ulrich, Hattingen, Elke, Pantel, Johannes, and Eckert, Gunter P.
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- 2024
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28. Relationship of Ki-67 index in biopsies of metastatic breast cancer tissue and circulating tumor cells (CTCs) at the time of biopsy collection
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Deutsch, Thomas M., Fischer, Chiara, Riedel, Fabian, Haßdenteufel, Kathrin, Michel, Laura L., Sütterlin, Marc, Riethdorf, Sabine, Pantel, Klaus, Wallwiener, Markus, Schneeweiss, Andreas, and Stefanovic, Stefan
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- 2024
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29. Mutation analysis in individual circulating tumor cells depicts intratumor heterogeneity in melanoma
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Mark Sementsov, Leonie Ott, Julian Kött, Alexander Sartori, Amelie Lusque, Sarah Degenhardt, Bertille Segier, Isabel Heidrich, Beate Volkmer, Rüdiger Greinert, Peter Mohr, Ronald Simon, Julia-Christina Stadler, Darryl Irwin, Claudia Koch, Antje Andreas, Benjamin Deitert, Verena Thewes, Andreas Trumpp, Andreas Schneeweiss, Yassine Belloum, Sven Peine, Harriett Wikman, Sabine Riethdorf, Stefan W Schneider, Christoffer Gebhardt, Klaus Pantel, and Laura Keller
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Circulating Tumor Cells ,Tumor ,Heterogeneity ,Melanoma ,Medicine (General) ,R5-920 ,Genetics ,QH426-470 - Abstract
Abstract Circulating tumor DNA (ctDNA) is the cornerstone of liquid biopsy diagnostics, revealing clinically relevant genomic aberrations from blood of cancer patients. Genomic analysis of single circulating tumor cells (CTCs) could provide additional insights into intra-patient heterogeneity, but it requires whole-genome amplification (WGA) of DNA, which might introduce bias. Here, we describe a novel approach based on mass spectrometry for mutation detection from individual CTCs not requiring WGA and complex bioinformatics pipelines. After establishment of our protocol on tumor cell line-derived single cells, it was validated on CTCs of 33 metastatic melanoma patients and the mutations were compared to those obtained from tumor tissue and ctDNA. Although concordance with tumor tissue was superior for ctDNA over CTC analysis, a larger number of mutations were found within CTCs compared to ctDNA (p = 0.039), including mutations in melanoma driver genes, or those associated with resistance to therapy or metastasis. Thus, our results demonstrate proof-of-principle data that CTC analysis can provide clinically relevant genomic information that is not redundant to tumor tissue or ctDNA analysis.
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- 2024
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30. Cefiderocol susceptibility of Achromobacter spp.: study of an accurately identified collection of 230 strains
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Vincent Jean-Pierre, Pauline Sorlin, Alix Pantel, Raphaël Chiron, Jean-Philippe Lavigne, Katy Jeannot, Hélène Marchandin, and Collaborative study group on antimicrobial resistance of Achromobacter spp.
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Achromobacter ,Opportunistic pathogen ,Cystic fibrosis ,Cefiderocol ,Susceptibility ,Therapeutics. Pharmacology ,RM1-950 ,Infectious and parasitic diseases ,RC109-216 ,Microbiology ,QR1-502 - Abstract
Abstract Background Achromobacter spp. are opportunistic pathogens, mostly infecting immunocompromised patients and patients with cystic fibrosis (CF) and considered as difficult-to-treat pathogens due to both intrinsic resistance and the possibility of acquired antimicrobial resistance. Species identification remains challenging leading to imprecise descriptions of resistance in each taxon. Cefiderocol is a broad-spectrum siderophore cephalosporin increasingly used in the management of Achromobacter infections for which susceptibility data remain scarce. We aimed to describe the susceptibility to cefiderocol of a collection of Achromobacter strains encompassing different species and isolation sources from CF or non-CF (NCF) patients. Methods We studied 230 Achromobacter strains (67 from CF, 163 from NCF patients) identified by nrdA gene-based analysis, with available susceptibility data for piperacillin–tazobactam, meropenem and trimethoprim–sulfamethoxazole. Minimal inhibitory concentrations (MICs) of cefiderocol were determined using the broth microdilution reference method according to EUCAST guidelines. Results Strains belonged to 15 species. A. xylosoxidans represented the main species (71.3%). MICs ranged from ≤ 0.015 to 16 mg/L with MIC50/90 of ≤ 0.015/0.5 mg/L overall and 0.125/2 mg/L against 27 (11.7%) meropenem-non-susceptible strains. Cefiderocol MICs were not related to CF/NCF origin or species although A. xylosoxidans MICs were statistically lower than those of other species considered as a whole. Considering the EUCAST non-species related breakpoint (2 mg/L), 228 strains (99.1%) were susceptible to cefiderocol. The two cefiderocol-resistant strains (A. xylosoxidans from CF patients) represented 3.7% of meropenem-non-susceptible strains and 12.5% of MDR strains. Conclusions Cefiderocol exhibited excellent in vitro activity against a large collection of accurately identified Achromobacter strains, irrespective of species and origin.
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- 2024
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31. Master corepressor inactivation through multivalent SLiM-induced polymerization mediated by the oncogene suppressor RAI2
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Nishit Goradia, Stefan Werner, Edukondalu Mullapudi, Sarah Greimeier, Lina Bergmann, Andras Lang, Haydyn Mertens, Aleksandra Węglarz, Simon Sander, Grzegorz Chojnowski, Harriet Wikman, Oliver Ohlenschläger, Gunhild von Amsberg, Klaus Pantel, and Matthias Wilmanns
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Science - Abstract
Abstract While the elucidation of regulatory mechanisms of folded proteins is facilitated due to their amenability to high-resolution structural characterization, investigation of these mechanisms in disordered proteins is more challenging due to their structural heterogeneity, which can be captured by a variety of biophysical approaches. Here, we used the transcriptional master corepressor CtBP, which binds the putative metastasis suppressor RAI2 through repetitive SLiMs, as a model system. Using cryo-electron microscopy embedded in an integrative structural biology approach, we show that RAI2 unexpectedly induces CtBP polymerization through filaments of stacked tetrameric CtBP layers. These filaments lead to RAI2-mediated CtBP nuclear foci and relieve its corepressor function in RAI2-expressing cancer cells. The impact of RAI2-mediated CtBP loss-of-function is illustrated by the analysis of a diverse cohort of prostate cancer patients, which reveals a substantial decrease in RAI2 in advanced treatment-resistant cancer subtypes. As RAI2-like SLiM motifs are found in a wide range of organisms, including pathogenic viruses, our findings serve as a paradigm for diverse functional effects through multivalent interaction-mediated polymerization by disordered proteins in healthy and diseased conditions.
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- 2024
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32. Integrating a multimodal lifestyle intervention with medical food in prodromal Alzheimer’s disease: the MIND-ADmini randomized controlled trial
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Charlotta Thunborg, Rui Wang, Anna Rosenberg, Shireen Sindi, Pia Andersen, Sandrine Andrieu, Laus M. Broersen, Nicola Coley, Celine Couderc, Celine Z. Duval, Gerd Faxen-Irving, Göran Hagman, Merja Hallikainen, Krister Håkansson, Eija Kekkonen, Jenni Lehtisalo, Nicholas Levak, Francesca Mangialasche, Johannes Pantel, Anders Rydström, Anna Stigsdotter-Neely, Anders Wimo, Tiia Ngandu, Hilkka Soininen, Tobias Hartmann, Alina Solomon, and Miia Kivipelto
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Alzheimer’s disease ,Lifestyle intervention ,Multimodal intervention ,Adherence ,Medical food ,Prevention ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) showed cognitive benefits from a multidomain lifestyle intervention in at-risk older people. The LipiDiDiet trial highlighted benefits of medical food in prodromal Alzheimer’s disease (AD). However, the feasibility and impact of multimodal interventions combining lifestyle with medical food in prodromal AD is unclear. Methods MIND-ADmini was a 6-month multinational (Sweden, Finland, Germany, France) proof-of-concept randomized controlled trial (RCT). Participants were 60–85 years old, had prodromal AD (International Working Group-1 criteria), and vascular/lifestyle risk factors. The parallel-group RCT had three arms: multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); multimodal lifestyle intervention + medical food (Fortasyn Connect); and regular health advice/care (control). Participants were randomized 1:1:1 (computer-generated allocation at each site). Outcome evaluators were blinded to randomization. Primary outcome was feasibility of the multimodal intervention, evaluated by recruitment rate during a 6-month recruitment phase, overall adherence in each intervention arm, and 6-month retention rate. Successful adherence was pre-specified as attending ≥ 40% of sessions/domain in ≥ 2/4 domains (lifestyle intervention), and consuming ≥ 60% of the medical food (lifestyle intervention + medical food). The secondary outcomes included adherence/participation to each intervention component and overall adherence to healthy lifestyle changes, measured using a composite score for healthy lifestyle. Cognitive assessments were included as exploratory outcomes, e.g. Clinical Dementia Rating scale. Results During September 2017-May 2019, 93 individuals were randomized (32 lifestyle intervention, 31 lifestyle + medical food, and 30 control group). Overall recruitment rate was 76.2% (64.8% during the first 6 months). Overall 6-month retention rate was 91.4% (lifestyle intervention 87.5%; lifestyle + medical food 90.3%; control 96.7%). Domain-specific adherence in the lifestyle intervention group was 71.9% to cognitive training, 78.1% exercise, 68.8% nutritional guidance, and 81.3% vascular risk management; and in the lifestyle + medical food group, 90.3% to cognitive training, 87.1% exercise, 80.7% nutritional guidance, 87.1% vascular risk management, and 87.1% medical food. Compared with control, both intervention arms showed healthy diet improvements (βLifestyle×Time = 1.11, P = 0.038; βLifestyle+medical food×Time = 1.43, P = 0.007); the lifestyle + medical food group also showed vascular risk reduction (P = 0.043) and less cognitive-functional decline (P
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- 2024
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33. Diagnostic leukapheresis reveals distinct phenotypes of NSCLC circulating tumor cells
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Lisa-Marie Rieckmann, Michael Spohn, Lisa Ruff, David Agorku, Lisa Becker, Alina Borchers, Jenny Krause, Roisin O’Reilly, Jurek Hille, Janna-Lisa Velthaus-Rusik, Niklas Beumer, Armin Günther, Lena Willnow, Charles D. Imbusch, Peter Iglauer, Ronald Simon, Sören Franzenburg, Hauke Winter, Michael Thomas, Carsten Bokemeyer, Nicola Gagliani, Christian F. Krebs, Martin Sprick, Olaf Hardt, Sabine Riethdorf, Andreas Trumpp, Nikolas H. Stoecklein, Sven Peine, Philipp Rosenstiel, Klaus Pantel, Sonja Loges, and Melanie Janning
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Circulating tumor cells ,Non-small cell lung cancer ,Single cell RNA sequencing ,Intratumor heterogeneity ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Circulating tumor cells (CTCs) hold immense promise for unraveling tumor heterogeneity and understanding treatment resistance. However, conventional methods, especially in cancers like non-small cell lung cancer (NSCLC), often yield low CTC numbers, hindering comprehensive analyses. This study addresses this limitation by employing diagnostic leukapheresis (DLA) to cancer patients, enabling the screening of larger blood volumes. To leverage DLA’s full potential, this study introduces a novel approach for CTC enrichment from DLAs. Methods DLA was applied to six advanced stage NSCLC patients. For an unbiased CTC enrichment, a two-step approach based on negative depletion of hematopoietic cells was used. Single-cell (sc) whole-transcriptome sequencing was performed, and CTCs were identified based on gene signatures and inferred copy number variations. Results Remarkably, this innovative approach led to the identification of unprecedented 3,363 CTC transcriptomes. The extensive heterogeneity among CTCs was unveiled, highlighting distinct phenotypes related to the epithelial-mesenchymal transition (EMT) axis, stemness, immune responsiveness, and metabolism. Comparison with sc transcriptomes from primary NSCLC cells revealed that CTCs encapsulate the heterogeneity of their primary counterparts while maintaining unique CTC-specific phenotypes. Conclusions In conclusion, this study pioneers a transformative method for enriching CTCs from DLA, resulting in a substantial increase in CTC numbers. This allowed the creation of the first-ever single-cell whole transcriptome in-depth characterization of the heterogeneity of over 3,300 NSCLC-CTCs. The findings not only confirm the diagnostic value of CTCs in monitoring tumor heterogeneity but also propose a CTC-specific signature that can be exploited for targeted CTC-directed therapies in the future. This comprehensive approach signifies a major leap forward, positioning CTCs as a key player in advancing our understanding of cancer dynamics and paving the way for tailored therapeutic interventions.
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- 2024
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34. HERC5 downregulation in non-small cell lung cancer is associated with altered energy metabolism and metastasis
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Svenja Schneegans, Jana Löptien, Angelika Mojzisch, Desirée Loreth, Oliver Kretz, Christoph Raschdorf, Annkathrin Hanssen, Antonia Gocke, Bente Siebels, Karthikeyan Gunasekaran, Yi Ding, Leticia Oliveira-Ferrer, Laura Brylka, Thorsten Schinke, Hartmut Schlüter, Ilkka Paatero, Hannah Voß, Stefan Werner, Klaus Pantel, and Harriet Wikman
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HERC5 ,NSCLC ,Metastasis ,DTC ,Cancer metabolism ,OXPHOS ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Metastasis is the leading cause of cancer-related death in non-small cell lung cancer (NSCLC) patients. We previously showed that low HERC5 expression predicts early tumor dissemination and a dismal prognosis in NSCLC patients. Here, we performed functional studies to unravel the mechanism underlying the “metastasis-suppressor” effect of HERC5, with a focus on mitochondrial metabolism pathways. Methods We assessed cell proliferation, colony formation potential, anchorage-independent growth, migration, and wound healing in NSCLC cell line models with HERC5 overexpression (OE) or knockout (KO). To study early tumor cell dissemination, we used these cell line models in zebrafish experiments and performed intracardial injections in nude mice. Mass spectrometry (MS) was used to analyze protein changes in whole-cell extracts. Furthermore, electron microscopy (EM) imaging, cellular respiration, glycolytic activity, and lactate production were used to investigate the relationships with mitochondrial energy metabolism pathways. Results Using different in vitro NSCLC cell line models, we showed that NSCLC cells with low HERC5 expression had increased malignant and invasive properties. Furthermore, two different in vivo models in zebrafish and a xenograft mouse model showed increased dissemination and metastasis formation (in particular in the brain). Functional enrichment clustering of MS data revealed an increase in mitochondrial proteins in vitro when HERC5 levels were high. Loss of HERC5 leads to an increased Warburg effect, leading to improved adaptation and survival under prolonged inhibition of oxidative phosphorylation. Conclusions Taken together, these results indicate that low HERC5 expression increases the metastatic potential of NSCLC in vitro and in vivo. Furthermore, HERC5-induced proteomic changes influence mitochondrial pathways, ultimately leading to alterations in energy metabolism and demonstrating its role as a new potential metastasis suppressor gene.
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- 2024
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35. On some properties of the compliance-volume fraction Pareto front in topology optimization useful for material selection
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Duriez, Edouard, Charlotte, Miguel, Azzaro-Pantel, Catherine, and Morlier, Joseph
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Mathematics - Optimization and Control - Abstract
Selecting the optimal material for a part designed through topology optimization is a complex problem. The shape and properties of the Pareto front plays an important role in this selection. In this paper we show that the compliance-volume fraction Pareto fronts of some topology optimization problems in linear elasticity share some useful properties. These properties provide an interesting point of view on the efficiency of topology optimization compared to other design approaches such as parametric structural optimization. We construct a simple meta-model which requires only one full topology optimization to fit the whole Pareto fronts. Precise Pareto fronts are obtained independently. The fast meta-model constructed has a maximum error of 6.4% with respect to these precise Pareto fronts, on the different problems tested. The selection of the optimal material is then successfully tested on the mass minimization of an MBB beam with an illustrative choice of 4 materials., Comment: including proofs
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- 2022
36. Expression profiling by high-throughput sequencing reveals GADD45, SMAD7, EGR-1 and HOXA3 activation in Myostatin (MSTN) and GDF11 treated myoblasts
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Platon Braun, Malik Alawi, Ceren Saygi, Klaus Pantel, and Amy J. Wagers
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GDF11 ,Myostatin ,RNA sequencing ,myoblasts ,gene expression ,Genetics ,QH426-470 - Abstract
Abstract Growth differentiation factor 11 (GDF11) and myostatin (MSTN/GDF8) are closely related members of the transforming growth factor β (TGFβ) superfamily, sharing structural homology. Despite these structural similarities, recent research has shed light on the distinct roles these ligands play within muscle tissue. This study aims to uncover both the differences and similarities in gene expression at the transcriptome level by utilizing RNA sequencing. We conducted experiments involving five distinct groups, each with three biological replicates, using C2C12 cell cultures. The cells were subjected to high-throughput profiling to investigate disparities in gene expression patterns following preconditioning with either GDF11 or MSTN at concentrations of 1 nM and 10 nM, respectively. In addition, control groups were established. Our research revealed concentration-dependent gene expression patterns, with 38 genes showing significant differences when compared to the control groups. Notably, GADD45, SMAD7, EGR-1, and HOXA3 exhibited significant differential expression. We also conducted an over-representation analysis, highlighting the activation of MAPK and JNK signaling pathways, along with GO-terms related to genes that negatively regulate metabolic processes, biosynthesis, and protein phosphorylation. This study unveiled the activation of several genes not previously discussed in existing literature whose full biological implications are yet to be determined in future research.
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- 2024
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37. Total-body PET/CT or LAFOV PET/CT? Axial field-of-view clinical classification
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Mingels, Clemens, Caobelli, Federico, Alavi, Abass, Sachpekidis, Christos, Wang, Meiyun, Nalbant, Hande, Pantel, Austin R., Shi, Hongcheng, Rominger, Axel, and Nardo, Lorenzo
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- 2024
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38. How to early integrate operational diagnosis objectives in model-driven engineering processes: A methodological proposal based on fault and behavior trees.
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Nikolena Christofi, Claude Baron, Xavier Pucel, Marc Pantel, David Canu, and Christophe Ducamp
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- 2024
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39. Short-term air pollution and temperature exposure and changes in the extracellular microRNA profile of Normative Aging Study (NAS) participants
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Danesh Yazdi, Mahdieh, Nassan, Feiby L, Kosheleva, Anna, Wang, Cuicui, Xu, Zongli, Di, Qian, Requia, Weeberb J, Comfort, Nicole T, Wu, Haotian, Laurent, Louise C, DeHoff, Peter, Vokonas, Pantel, Baccarelli, Andrea A, and Schwartz, Joel D
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Genetics ,Aging ,Climate-Related Exposures and Conditions ,Biotechnology ,Good Health and Well Being ,Humans ,Air Pollutants ,Air Pollution ,Environmental Exposure ,MicroRNAs ,Nitrogen Dioxide ,Ozone ,Particulate Matter ,Temperature ,Air pollution ,microRNA ,Particulate matter ,Nitrogen dioxide ,Ambient temperature ,Environmental Sciences - Abstract
BackgroundWhile the health effects of air pollution and temperature are widely studied, the molecular effects are poorly understood. Extracellular microRNAs (ex-miRNAs) have the potential to serve as diagnostic or prognostic biomarkers and/or to act as intercellular signaling molecules that mediate the effects of environmental exposures on health outcomes.MethodsWe examined the relationship between short-term exposure to air pollution and ambient temperature and the ex-miRNA profiles of participants in the Normative Aging Study (NAS) from 1999 to 2015. Our exposures were defined as same-day, two-day, three-day, one-week, two-week, and three-week moving averages of PM2.5, NO2, O3, and temperature which were derived from high-resolution spatio-temporal models. The ex-miRNA profiles of the subjects were obtained during follow-up visits. We analyzed the data using a longitudinal quantile regression model adjusted for individual covariates, batch effects, and time trends. We adjusted for multiple comparisons using a false discovery rate (FDR) correction. Ex-miRNAs that were significantly associated with exposures were further investigated using pathway analyses.ResultsWe found that all the examined exposures were associated with changes in ex-miRNA profiles in our study, particularly PM2.5 which was responsible for most of the statistically significant results. We found 110 statistically significant exposure-outcome relationships that revealed associations with the levels of 52 unique ex-miRNAs. Pathway analyses showed these ex-miRNAs have been linked to target mRNAs, genes, and biological mechanisms that could affect virtually every organ system, and as such may be linked to multiple clinical disease presentations such as cardiovascular disease, respiratory disease, and neurological disease.ConclusionsAir pollution and temperature exposures were significantly associated with alterations in the ex-miRNA profiles of NAS subjects with possible biological consequences.
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- 2023
40. Extracellular Vesicle-Encapsulated microRNAs as Novel Biomarkers of Lung Health.
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Eckhardt, Christina M, Gambazza, Simone, Bloomquist, Tessa R, De Hoff, Peter, Vuppala, Aishwarya, Vokonas, Pantel S, Litonjua, Augusto A, Sparrow, David, Parvez, Faruque, Laurent, Louise C, Schwartz, Joel, Baccarelli, Andrea A, and Wu, Haotian
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Genetics ,Lung ,Clinical Research ,Prevention ,Biotechnology ,Respiratory ,Good Health and Well Being ,Humans ,MicroRNAs ,Lung Injury ,Longitudinal Studies ,Prospective Studies ,Biomarkers ,Extracellular Vesicles ,extracellular vesicles ,microRNAs ,lung function ,spirometry ,Medical and Health Sciences ,Respiratory System - Abstract
Rationale: Early detection of respiratory diseases is critical to facilitate delivery of disease-modifying interventions. Extracellular vesicle-enriched microRNAs (EV-miRNAs) may represent reliable markers of early lung injury. Objectives: Evaluate associations of plasma EV-miRNAs with lung function. Methods: The prospective NAS (Normative Aging Study) collected plasma EV-miRNA measurements from 1996-2015 and spirometry every 3-5 years through 2019. Associations of EV-miRNAs with baseline lung function were modeled using linear regression. To complement the individual miRNA approach, unsupervised machine learning was used to identify clusters of participants with distinct EV-miRNA profiles. Associations of EV-miRNA profiles with multivariate latent longitudinal lung function trajectories were modeled using log binomial regression. Biological functions of significant EV-miRNAs were explored using pathway analyses. Results were replicated in an independent sample of NAS participants and in the HEALS (Health Effects of Arsenic Longitudinal Study). Measurements and Main Results: In the main cohort of 656 participants, 51 plasma EV-miRNAs were associated with baseline lung function (false discovery rate-adjusted P value
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- 2023
41. Continuous infusion of meropenem–vaborbactam for a KPC-3-producing Klebsiella pneumoniae bloodstream infection in a critically ill patient with augmented renal clearance
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Larcher, Romaric, Laffont-Lozes, Paul, Naciri, Tayma, Bourgeois, Pierre-Marie, Gandon, Cléa, Magnan, Chloé, Pantel, Alix, and Sotto, Albert
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- 2023
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42. Leichte kognitive Beeinträchtigung (MCI) in der altersmedizinischen Praxis: Patientenorientierung, Diagnostik, Behandlung und Ethik
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Frölich, Lutz, von Arnim, Christine, Bohlken, Jens, Pantel, Johannes, Peters, Oliver, and Förstl, Hans
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- 2023
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43. Coarse-to-Fine Sparse Sequential Recommendation
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Li, Jiacheng, Zhao, Tong, Li, Jin, Chan, Jim, Faloutsos, Christos, Karypis, George, Pantel, Soo-Min, and McAuley, Julian
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Computer Science - Information Retrieval ,Computer Science - Artificial Intelligence - Abstract
Sequential recommendation aims to model dynamic user behavior from historical interactions. Self-attentive methods have proven effective at capturing short-term dynamics and long-term preferences. Despite their success, these approaches still struggle to model sparse data, on which they struggle to learn high-quality item representations. We propose to model user dynamics from shopping intents and interacted items simultaneously. The learned intents are coarse-grained and work as prior knowledge for item recommendation. To this end, we present a coarse-to-fine self-attention framework, namely CaFe, which explicitly learns coarse-grained and fine-grained sequential dynamics. Specifically, CaFe first learns intents from coarse-grained sequences which are dense and hence provide high-quality user intent representations. Then, CaFe fuses intent representations into item encoder outputs to obtain improved item representations. Finally, we infer recommended items based on representations of items and corresponding intents. Experiments on sparse datasets show that CaFe outperforms state-of-the-art self-attentive recommenders by 44.03% NDCG@5 on average., Comment: Accepted as conference paper at SIGIR 2022
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- 2022
44. Emergence of multidrug-resistant Staphylococcus haemolyticus in neonatal intensive care unit in Southern France, a genomic study
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Chloé Magnan, Madjid Morsli, Florian Salipante, Blandine Thiry, Julie El Attar, Massimo Di Maio, Maryam Safaria, Tu-Anh Tran, Catherine Dunyach-Remy, Jérôme Ory, Brigitte Richaud-Morel, Albert Sotto, Alix Pantel, and Jean-Philippe Lavigne
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Staphylococcus haemolyticus ,neonatal intensive care unit ,multidrug resistance ,emergence ,whole-genome sequencing ,ST29 ,Infectious and parasitic diseases ,RC109-216 ,Microbiology ,QR1-502 - Abstract
ABSTRACTAn emergence of multidrug-resistant (MDR) Staphylococcus haemolyticus has been observed in the neonatal intensive care unit (NICU) of Nîmes University Hospital in southern France. A case–control analysis was conducted on 96 neonates, to identify risk factors associated with S. haemolyticus infection, focusing on clinical outcomes. Forty-eight MDR S. haemolyticus strains, isolated from neonates between October 2019 and July 2022, were investigated using routine in vitro procedures and whole-genome sequencing. Additionally, five S. haemolyticus isolates from adult patients were sequenced to identify clusters circulating within the hospital environment. The incidence of neonatal S. haemolyticus was significantly associated with low birth weight, lower gestational age, and central catheter use (p
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- 2024
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45. Diabetes mellitus im höheren Lebensalter: Diagnostik, Therapie und Versorgung
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Johannes Pantel, Rupert Püllen and Johannes Pantel, Rupert Püllen
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- 2024
46. Accelerated aging procedure of epoxy structural adhesive for marine offshore applications
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Marco Lamberti, Aurélien Maurel-Pantel, and Frédéric Lebon
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Hygro-thermal environment ,Adhesive connections ,Ageing ,Mechanical properties ,Materials of engineering and construction. Mechanics of materials ,TA401-492 - Abstract
Knowledge of the long-term performance of adhesive connections is undoubtedly of paramount importance to enable their deployment in civil, mechanical, and other engineering applications. Over time, adverse environmental conditions can strongly influence the performance of adhesive joints leading to a progressive deterioration of their initial mechanical properties. The use of adhesive connections for secondary structures in offshore applications is a technology that allows for the rapid creation of structural members that, however, cannot ignore the influence of hydrothermal effects on mechanical performance due to environmental conditions. In this context, the investigation of the hygrothermal durability of adhesive connections was undertaken through an extensive experimental programme. More specifically, 130 cylindrical steel joints bonded with a commercially epoxy resin for structural applications were tested in Mode I using an Arcan-modified device. Prior to test, the specimens were placed in climatic ovens capable of combining the effects of temperature and humidity for approximately 320 days. In addition, the glass transition temperature, Tg, was assessed by employing the differential scanning calorimeter (DSC) technique to correctly define the experimental ageing conditions. The experimental results show how ageing conditions influence the mechanical properties of the epoxy resin investigated. Finally, some predictive formulations are proposed to calculate the loss of strength of adhesive joints over time.
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- 2024
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47. Extracellular microRNA and cognitive function in a prospective cohort of older men: The Veterans Affairs Normative Aging Study
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Comfort, Nicole, Wu, Haotian, De Hoff, Peter, Vuppala, Aishwarya, Vokonas, Pantel S, Spiro, Avron, Weisskopf, Marc, Coull, Brent A, Laurent, Louise C, Baccarelli, Andrea A, and Schwartz, Joel
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Mental Health ,Dementia ,Neurosciences ,Aging ,Biotechnology ,Alzheimer's Disease ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Brain Disorders ,Neurodegenerative ,Infectious Diseases ,Acquired Cognitive Impairment ,Genetics ,1.1 Normal biological development and functioning ,Underpinning research ,Neurological ,Aged ,Cognition ,Cognitive Dysfunction ,Cross-Sectional Studies ,Fatty Acids ,Humans ,Male ,MicroRNAs ,Prospective Studies ,Veterans ,plasma ,extracellular RNA ,RNA-seq ,microRNA ,cognitive decline ,cognitive impairment ,Biochemistry and Cell Biology ,Physiology ,Oncology and Carcinogenesis ,Developmental Biology - Abstract
BackgroundAging-related cognitive decline is an early symptom of Alzheimer's disease and other dementias, and on its own can have substantial consequences on an individual's ability to perform important everyday functions. Despite increasing interest in the potential roles of extracellular microRNAs (miRNAs) in central nervous system (CNS) pathologies, there has been little research on extracellular miRNAs in early stages of cognitive decline. We leverage the longitudinal Normative Aging Study (NAS) cohort to investigate associations between plasma miRNAs and cognitive function among cognitively normal men.MethodsThis study includes data from up to 530 NAS participants (median age: 71.0 years) collected from 1996 to 2013, with a total of 1,331 person-visits (equal to 2,471 years of follow up). Global cognitive function was assessed using the Mini-Mental State Examination (MMSE). Plasma miRNAs were profiled using small RNA sequencing. Associations of expression of 381 miRNAs with current cognitive function and rate of change in cognitive function were assessed using linear regression (N = 457) and linear mixed models (N = 530), respectively.ResultsIn adjusted models, levels of 2 plasma miRNAs were associated with higher MMSE scores (p < 0.05). Expression of 33 plasma miRNAs was associated with rate of change in MMSE scores over time (p < 0.05). Enriched KEGG pathways for miRNAs associated with concurrent MMSE and MMSE trajectory included Hippo signaling and extracellular matrix-receptor interactions. Gene targets of miRNAs associated with MMSE trajectory were additionally associated with prion diseases and fatty acid biosynthesis.ConclusionsCirculating miRNAs were associated with both cross-sectional cognitive function and rate of change in cognitive function among cognitively normal men. Further research is needed to elucidate the potential functions of these miRNAs in the CNS and investigate relationships with other neurological outcomes.
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- 2022
48. Abbreviated scan protocols to capture 18F-FDG kinetics for long axial FOV PET scanners.
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Viswanath, Varsha, Sari, Hasan, Pantel, Austin, Conti, Maurizio, Daube-Witherspoon, Margaret, Mingels, Clemens, Alberts, Ian, Eriksson, Lars, Shi, Kuangyu, Rominger, Axel, and Karp, Joel
- Subjects
18F-FDG flux ,Dynamic imaging ,FDG ,Fluorodeoxyglucose F18 ,Humans ,Kinetics ,Neoplasms ,Positron-Emission Tomography ,Radionuclide Imaging - Abstract
PURPOSE: Kinetic parameters from dynamic 18F-fluorodeoxyglucose (FDG) imaging offer complementary insights to the study of disease compared to static clinical imaging. However, dynamic imaging protocols are cumbersome due to the long acquisition time. Long axial field-of-view (LAFOV) PET scanners (> 70 cm) have two advantages for dynamic imaging over clinical PET scanners with a standard axial field-of-view (SAFOV; 16-30 cm). The large axial coverage enables multi-organ dynamic imaging in a single bed position, and the high sensitivity may enable clinically routine abbreviated dynamic imaging protocols. METHODS: In this work, we studied two abbreviated protocols using data from a 65-min dynamic 18F-FDG scan: (A) dynamic imaging immediately post-injection (p.i.) for variable durations, and (B) dynamic imaging immediately p.i. for variable durations plus a 1-h p.i. (5-min-long) datapoint. Nine cancer patients were imaged on the Biograph Vision Quadra (Siemens Healthineers). Time-activity curves over the lesions (N = 39) were fitted using the Patlak graphical analysis and a 2-tissue-compartment (2C, k4 = 0) model for variable scan durations (5-60 min). Kinetic parameters from the complete dataset served as the reference. Lesions from all cancers were grouped into low, medium, and high flux groups, and bias and precision of Ki (Patlak) and Ki, K1, k2, and k3 (2C) were calculated for each group. RESULTS: Using only early dynamic data with the 2C (or Patlak) model, accurate quantification of Ki required at least 50 (or 55) min of dynamic data for low flux lesions, at least 30 (or 40) min for medium flux lesions, and at least 15 (or 20) min for high flux lesions to achieve both 10% bias and precision. The addition of the final (5-min) datapoint allowed for accurate quantification of Ki with a bias and precision of 10% using only 10-15 min of early dynamic data for either model. CONCLUSION: Dynamic imaging for 10-15 min immediately p.i. followed by a 5-min scan at 1-h p.i can accurately and precisely quantify 18F-FDG on a long axial FOV scanner, potentially allowing for more widespread use of dynamic 18F-FDG imaging.
- Published
- 2022
49. Paving the way for low-carbon hydrogen supply chain deployment by exploring the potential of renewable energies and multisectoral hydrogen demand: Case study of France
- Author
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Luise, Renato, Brisse, Annabelle, and Azzaro-Pantel, Catherine
- Published
- 2024
- Full Text
- View/download PDF
50. Functional characterization of PI3K C2 domain mutations detected in breast cancer circulating tumor cells and metastatic cells
- Author
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Smit, Daniel J., Brauer, Helena, Horn, Stefan, Yigit, Gökhan, Haider, Marie-Therese, Pogenberg, Vivian, Schumacher, Udo, Pantel, Klaus, and Jücker, Manfred
- Published
- 2024
- Full Text
- View/download PDF
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