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Article ; Online: Clinical applications of circulating tumor DNA in central nervous system lymphoma.

Foerster, Anna Katharina / Lauer, Eliza M / Scherer, Florian

2023 Volume 60, Issue 3, Page(s) 150–156

Abstract: Detection and characterization of circulating tumor DNA (ctDNA) in body fluids have the potential to revolutionize management of patients with lymphoma. Minimal access to malignant DNA through a simple blood draw or lumbar puncture is particularly ... ...

Abstract	Detection and characterization of circulating tumor DNA (ctDNA) in body fluids have the potential to revolutionize management of patients with lymphoma. Minimal access to malignant DNA through a simple blood draw or lumbar puncture is particularly appealing for CNS lymphomas (CNSL), which cannot be easily or repeatedly sampled without invasive surgeries. Profiling of ctDNA provides a real-time snapshot of the genetic composition in patients with CNSL and enables ultrasensitive quantification of lymphoma burden at any given time point during the course of the disease. Here, we broadly review technical challenges of ctDNA identification in CNSL, recent advances of innovative liquid biopsy technologies, potential clinical applications of ctDNA and how it may improve CNSL risk stratification, outcome prediction, and monitoring of measurable residual disease. Finally, we discuss clinical trials and scenarios in which ctDNA could be implemented to guide risk-adapted and personalized treatment decisions.
MeSH term(s)	Humans ; Circulating Tumor DNA/genetics ; Lymphoma/genetics ; Liquid Biopsy ; Central Nervous System Neoplasms/genetics ; Central Nervous System ; Biomarkers, Tumor/genetics
Chemical Substances	Circulating Tumor DNA ; Biomarkers, Tumor
Language	English
Publishing date	2023-07-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	206923-4
ISSN	1532-8686 ; 0037-1963
ISSN (online)	1532-8686
ISSN	0037-1963
DOI	10.1053/j.seminhematol.2023.06.007
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Article ; Online: The Patient Typology about deprescribing and medication-related decisions: A quantitative exploration.

Weir, Kristie Rebecca / Scherer, Aaron M / Vordenberg, Sarah E / Streit, Sven / Jansen, Jesse / Jungo, Katharina Tabea

Basic & clinical pharmacology & toxicology

2023 Volume 134, Issue 1, Page(s) 39–50

Abstract: This study aimed to test the adequacy of a quantitative measure of our qualitatively developed Patient Typology-categories of older adults' attitudes towards medicines and medicine decision-making-and identify characteristics associated with each ... ...

Abstract	This study aimed to test the adequacy of a quantitative measure of our qualitatively developed Patient Typology-categories of older adults' attitudes towards medicines and medicine decision-making-and identify characteristics associated with each Typology. We conducted secondary data analyses of a subset of survey item measures of adults (≥65 years) who were members of online survey panels in Australia, the United Kingdom, the United States and the Netherlands (n = 4688). Multinomial logistic regression analyses assessed associations between demographic, psychosocial and medication-related measures. Mean age was 71.5 (5), and 47.5% of participants were female. Factors associated with an increased likelihood of identifying with Typology 1 'Attached to medicines' over Typology 2 'Open to deprescribing' were higher positive attitude towards polypharmacy (RRR = 1.12, p = <0.001) and higher need for certainty (RRR = 1.11, p = 0.039). Factors associated with an increased likelihood of identifying with Typology 3 'Defers (medication decision-making) to others' over Typology 2 were older age (RRR = 1.47 per 10-year age increase, p = <0.001) and a decreased likelihood of prior deprescribing experience (RRR = 0.73, p = 0.033). This study provides validation of the Typology with large samples from four countries, with the quantitatively-measured typologies generally aligning with the qualitatively derived categories. Our Patient Typology measure provides a succinct way researchers can assess attitudes towards deprescribing.
MeSH term(s)	Humans ; Female ; Aged ; Male ; Deprescriptions ; Clinical Decision-Making ; Polypharmacy ; Surveys and Questionnaires ; Australia
Language	English
Publishing date	2023-07-03
Publishing country	England
Document type	Journal Article
ZDB-ID	2134679-3
ISSN	1742-7843 ; 1742-7835
ISSN (online)	1742-7843
ISSN	1742-7835
DOI	10.1111/bcpt.13911
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Article ; Online: Asking the generalist - evaluation of a General Practice rounding and consult service.

Schmalstieg-Bahr, Katharina / MacDonald, Sophia / Pohontsch, Nadine / Debus, Sebastian / Scherer, Martin

BMC primary care

2024 Volume 25, Issue 1, Page(s) 113

Abstract: Background: Vascular surgery patients admitted to the hospital are often multimorbid. In case of questions regarding chronic medical problems different specialties are consulted, which leads to a high number of treating physicians and possibly ... ...

Abstract	Background: Vascular surgery patients admitted to the hospital are often multimorbid. In case of questions regarding chronic medical problems different specialties are consulted, which leads to a high number of treating physicians and possibly contradicting recommendations. The General Practitioner´s (GP) view could minimize this problem. However, it is unknown for which medical problems a GP would be consulted and if regular GP-involvement during rounds would be considered helpful by the specialists. The aim of this study was to establish and describe a General Practice rounding service (GP-RS), to evaluate if the GP-RS is doable in a tertiary care hospital and beneficial to the specialists and to explore GP-consult indications. Methods: The GP-RS was established as a pilot project. Between June-December 2020, a board-certified GP from the Department of General Practice and Primary Care, University Medical Center Hamburg-Eppendorf (UKE) joined the vascular surgery team (UKE) once-weekly on rounds. The project was evaluated using a multi-methods approach: semi-structured qualitative interviews were conducted with vascular surgery physicians that had either participated in the GP-RS (G1), had not participated (G2), other specialists usually conducting consults on the vascular surgery floor (G3) and with the involved GP (G4). Interviews were analyzed using Kuckartz' qualitative content analysis. In addition, two sets of quantitative data were descriptively analyzed focusing on the reasons for a GP-consult: one set from the GP-RS and one from an established, conventional "as needed" GP-consult service. Results: 15 interviews were conducted. Physicians perceived the GP-RS as beneficial, especially for surgical patients (G1-3). Optimizing medication, avoiding unnecessary consults and a learning effect for physicians in training (G1-4) were named as other benefits. Critical voices saw an increased workload through the GP-RS (G1, G3) and some consult requests as too specific for a GP (G1-3). Based on data from 367 vascular surgery patients and 80 conventional GP-consults, the most common reasons for a GP-consult were cardiovascular diseases including hypertension and diabetes. Conclusions: A GP-RS is doable in a tertiary care hospital. Studies of GP co-management model with closer follow ups would be needed to objectively improve patient care and reduce the overall number of consults. Trial registration: Not applicable.
MeSH term(s)	Humans ; Pilot Projects ; Family Practice ; Referral and Consultation ; General Practice ; Academic Medical Centers
Language	English
Publishing date	2024-04-16
Publishing country	England
Document type	Journal Article
ISSN	2731-4553
ISSN (online)	2731-4553
DOI	10.1186/s12875-024-02353-0
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Article ; Online: ERnet: a tool for the semantic segmentation and quantitative analysis of endoplasmic reticulum topology.

Lu, Meng / Christensen, Charles N / Weber, Jana M / Konno, Tasuku / Läubli, Nino F / Scherer, Katharina M / Avezov, Edward / Lio, Pietro / Lapkin, Alexei A / Kaminski Schierle, Gabriele S / Kaminski, Clemens F

Nature methods

2023 Volume 20, Issue 4, Page(s) 569–579

Abstract: The ability to quantify structural changes of the endoplasmic reticulum (ER) is crucial for understanding the structure and function of this organelle. However, the rapid movement and complex topology of ER networks make this challenging. Here, we ... ...

Abstract	The ability to quantify structural changes of the endoplasmic reticulum (ER) is crucial for understanding the structure and function of this organelle. However, the rapid movement and complex topology of ER networks make this challenging. Here, we construct a state-of-the-art semantic segmentation method that we call ERnet for the automatic classification of sheet and tubular ER domains inside individual cells. Data are skeletonized and represented by connectivity graphs, enabling precise and efficient quantification of network connectivity. ERnet generates metrics on topology and integrity of ER structures and quantifies structural change in response to genetic or metabolic manipulation. We validate ERnet using data obtained by various ER-imaging methods from different cell types as well as ground truth images of synthetic ER structures. ERnet can be deployed in an automatic high-throughput and unbiased fashion and identifies subtle changes in ER phenotypes that may inform on disease progression and response to therapy.
MeSH term(s)	Semantics ; Endoplasmic Reticulum/metabolism
Language	English
Publishing date	2023-03-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2169522-2
ISSN	1548-7105 ; 1548-7091
ISSN (online)	1548-7105
ISSN	1548-7091
DOI	10.1038/s41592-023-01815-0
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Article ; Online: Near-native state imaging by cryo-soft-X-ray tomography reveals remodelling of multiple cellular organelles during HSV-1 infection.

Nahas, Kamal L / Connor, Viv / Scherer, Katharina M / Kaminski, Clemens F / Harkiolaki, Maria / Crump, Colin M / Graham, Stephen C

PLoS pathogens

2022 Volume 18, Issue 7, Page(s) e1010629

Abstract: Herpes simplex virus-1 (HSV-1) is a large, enveloped DNA virus and its assembly in the cell is a complex multi-step process during which viral particles interact with numerous cellular compartments such as the nucleus and organelles of the secretory ... ...

Abstract	Herpes simplex virus-1 (HSV-1) is a large, enveloped DNA virus and its assembly in the cell is a complex multi-step process during which viral particles interact with numerous cellular compartments such as the nucleus and organelles of the secretory pathway. Transmission electron microscopy and fluorescence microscopy are commonly used to study HSV-1 infection. However, 2D imaging limits our understanding of the 3D geometric changes to cellular compartments that accompany infection and sample processing can introduce morphological artefacts that complicate interpretation. In this study, we used soft X-ray tomography to observe differences in whole-cell architecture between HSV-1 infected and uninfected cells. To protect the near-native structure of cellular compartments we used a non-disruptive sample preparation technique involving rapid cryopreservation, and a fluorescent reporter virus was used to facilitate correlation of structural changes with the stage of infection in individual cells. We observed viral capsids and assembly intermediates interacting with nuclear and cytoplasmic membranes. Additionally, we observed differences in the morphology of specific organelles between uninfected and infected cells. The local concentration of cytoplasmic vesicles at the juxtanuclear compartment increased and their mean width decreased as infection proceeded, and lipid droplets transiently increased in size. Furthermore, mitochondria in infected cells were elongated and highly branched, suggesting that HSV-1 infection alters the dynamics of mitochondrial fission/fusion. Our results demonstrate that high-resolution 3D images of cellular compartments can be captured in a near-native state using soft X-ray tomography and have revealed that infection causes striking changes to the morphology of intracellular organelles.
MeSH term(s)	Animals ; Cell Nucleus ; Chlorocebus aethiops ; Herpes Simplex/diagnostic imaging ; Herpesvirus 1, Human/chemistry ; Tomography, X-Ray ; Vero Cells
Language	English
Publishing date	2022-07-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7374
ISSN (online)	1553-7374
ISSN	1553-7374
DOI	10.1371/journal.ppat.1010629
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Book ; Audio / Video ; Online: Pseudomonaden in Rohmilch

Gieschler, Stefanie / Hoffmann, Katharina / Lücking, Genia / Wenning, Mareike / Hetzer, Birgit / Böhnlein, Christina / Scherer, Siegfried / Franz, Charles M. A. P.

(k)ein Problem für deutsche Milcherzeuger

2022

Keywords	Text ; ddc:610
Language	German
Publishing country	de
Document type	Book ; Audio / Video ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Ethical and coordinative challenges in setting up a national cohort study during the COVID-19 pandemic in Germany.

Tilch, Katharina / Hopff, Sina M / Appel, Katharina / Kraus, Monika / Lorenz-Depiereux, Bettina / Pilgram, Lisa / Anton, Gabi / Berger, Sarah / Geisler, Ramsia / Haas, Kirsten / Illig, Thomas / Krefting, Dagmar / Lorbeer, Roberto / Mitrov, Lazar / Muenchhoff, Maximilian / Nauck, Matthias / Pley, Christina / Reese, Jens-Peter / Rieg, Siegbert /

Scherer, Margarete / Stecher, Melanie / Stellbrink, Christoph / Valentin, Heike / Winter, Christof / Witzenrath, Martin / Vehreschild, J Janne

BMC medical ethics

2023 Volume 24, Issue 1, Page(s) 84

Abstract: With the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), global researchers were confronted with major challenges. The German National Pandemic Cohort Network (NAPKON) was launched in fall 2020 to effectively leverage resources ... ...

Abstract	With the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), global researchers were confronted with major challenges. The German National Pandemic Cohort Network (NAPKON) was launched in fall 2020 to effectively leverage resources and bundle research activities in the fight against the coronavirus disease 2019 (COVID-19) pandemic. We analyzed the setup phase of NAPKON as an example for multicenter studies in Germany, highlighting challenges and optimization potential in connecting 59 university and nonuniversity study sites. We examined the ethics application process of 121 ethics submissions considering durations, annotations, and outcomes. Study site activation and recruitment processes were investigated and related to the incidence of SARS-CoV-2 infections. For all initial ethics applications, the median time to a positive ethics vote was less than two weeks and 30 of these study sites (65%) joined NAPKON within less than three weeks each. Electronic instead of postal ethics submission (9.5 days (Q1: 5.75, Q3: 17) vs. 14 days (Q1: 11, Q3: 26), p value = 0.01) and adoption of the primary ethics vote significantly accelerated the ethics application process. Each study center enrolled a median of 37 patients during the 14-month observation period, with large differences depending on the health sector. We found a positive correlation between recruitment performance and COVID-19 incidence as well as hospitalization incidence. Our analysis highlighted the challenges and opportunities of the federated system in Germany. Digital ethics application tools, adoption of a primary ethics vote and standardized formal requirements lead to harmonized and thus faster study initiation processes during a pandemic.
MeSH term(s)	Humans ; COVID-19/epidemiology ; SARS-CoV-2 ; Pandemics ; Cohort Studies ; Germany/epidemiology
Language	English
Publishing date	2023-10-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2041552-7
ISSN	1472-6939 ; 1472-6939
ISSN (online)	1472-6939
ISSN	1472-6939
DOI	10.1186/s12910-023-00959-0
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Article: Combining sample expansion and light sheet microscopy for the volumetric imaging of virus-infected cells with super-resolution.

Mascheroni, Luca / Scherer, Katharina M / Manton, James D / Ward, Edward / Dibben, Oliver / Kaminski, Clemens F

Biomedical optics express

2020 Volume 11, Issue 9, Page(s) 5032–5044

Abstract: Expansion microscopy is a sample preparation technique that enables the optical imaging of biological specimens at super-resolution owing to their physical magnification, which is achieved through water-absorbing polymers. The technique uses readily ... ...

Abstract	Expansion microscopy is a sample preparation technique that enables the optical imaging of biological specimens at super-resolution owing to their physical magnification, which is achieved through water-absorbing polymers. The technique uses readily available chemicals and does not require sophisticated equipment, thus offering super-resolution to laboratories that are not microscopy-specialised. Here we present a protocol combining sample expansion with light sheet microscopy to generate high-contrast, high-resolution 3D reconstructions of whole virus-infected cells. The results are superior to those achievable with comparable imaging modalities and reveal details of the infection cycle that are not discernible before expansion. An image resolution of approximately 95 nm could be achieved in samples labelled in 3 colours. We resolve that the viral nucleoprotein is accumulated at the membrane of vesicular structures within the cell cytoplasm and how these vesicles are positioned relative to cellular structures. We provide detailed guidance and a video protocol for the optimal application of the method and demonstrate its potential to study virus-host cell interactions.
Language	English
Publishing date	2020-08-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	2572216-5
ISSN	2156-7085
ISSN	2156-7085
DOI	10.1364/BOE.399404
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Article ; Online: EAP45 association with budding HIV-1: Kinetics and domain requirements.

Meng, Bo / Vallejo Ramirez, Pedro P / Scherer, Katharina M / Bruggeman, Ezra / Kenyon, Julia C / Kaminski, Clemens F / Lever, Andrew M

Traffic (Copenhagen, Denmark)

2021 Volume 22, Issue 12, Page(s) 439–453

Abstract: A number of viruses including HIV use the ESCRT system to bud from the infected cell. We have previously confirmed biochemically that ESCRT-II is involved in this process in HIV-1 and have defined the molecular domains that are important for this. Here, ... ...

Abstract	A number of viruses including HIV use the ESCRT system to bud from the infected cell. We have previously confirmed biochemically that ESCRT-II is involved in this process in HIV-1 and have defined the molecular domains that are important for this. Here, using SNAP-tag fluorescent labelling and both fixed and live cell imaging we show that the ESCRT-II component EAP45 colocalises with the HIV protein Gag at the plasma membrane in a temporal and quantitative manner, similar to that previously shown for ALIX and Gag. We show evidence that a proportion of EAP45 may be packaged within virions, and we confirm the importance of the N terminus of EAP45 and specifically the H0 domain in this process. By contrast, the Glue domain of EAP45 is more critical for recruitment during cytokinesis, emphasising that viruses have ways of recruiting cellular components that may be distinct from those used by some cellular processes. This raises the prospect of selective interference with the pathway to inhibit viral function while leaving cellular functions relatively unperturbed.
MeSH term(s)	Endosomal Sorting Complexes Required for Transport/metabolism ; HIV Infections ; HIV-1/metabolism ; Humans ; Kinetics
Chemical Substances	Endosomal Sorting Complexes Required for Transport
Language	English
Publishing date	2021-10-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1483852-7
ISSN	1600-0854 ; 1398-9219
ISSN (online)	1600-0854
ISSN	1398-9219
DOI	10.1111/tra.12820
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Article: The Role of General Practice in Complex Health Care Systems.

Schmalstieg-Bahr, Katharina / Popert, Uwe Wolfgang / Scherer, Martin

Frontiers in medicine

2021 Volume 8, Page(s) 680695

Abstract: According to the WHO, in a complex system, "there are so many interacting parts that it is difficult (…), to predict the behavior of the system based on knowledge of its component parts. "In countries without general practitioner (GP)-gatekeeping, the ... ...

Abstract	According to the WHO, in a complex system, "there are so many interacting parts that it is difficult (…), to predict the behavior of the system based on knowledge of its component parts. "In countries without general practitioner (GP)-gatekeeping, the number of possible interactions and therefore the complexity increases. Patients may consult any doctor without contacting their GP. Family medicine core values, e.g., comprehensive care, and core tasks, e.g., care coordination, might be harder to implement and maintain. How are GPs perceived and how do they perceive themselves if no GP-gatekeeping exists? Does the absence of any GP-gatekeeping influence family medicine core values? A PubMed and Cochrane search was performed. The results are summarized in form of a narrative review. Four perspectives regarding the GP's role were identified. The GPs' self-perception regarding family medicine core values and tasks is independent of their function as gatekeepers, but they appreciate this role. Patient satisfaction is also independent of the health care system. Depending on the acquisition of income, specialists have different opinions of GP-gatekeeping. Policymakers want GPs to play a central role within the health care system, but do not commit to full gatekeeping. The GPs and policymakers emphasize the importance of family medicine specialty training. Further international studies are needed to determine if family medicine core values and tasks can be better accomplished by GP-gatekeeping. Specialty training should be mandatory in all countries to enable GPs to fulfill these values and tasks and to act as coordinators and/or gatekeepers.
Language	English
Publishing date	2021-11-25
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2021.680695
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