| 451. |
- Hilbert, Kevin, et al.
(författare)
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Cortical and Subcortical Brain Alterations in Specific Phobia and Its Animal and Blood-Injection-Injury Subtypes: A Mega-Analysis From the ENIGMA Anxiety Working Group.
- 2024
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Ingår i: The American Journal of Psychiatry. - 1535-7228. ; 181:8, s. 728-740
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Tidskriftsartikel (refereegranskat)abstract
- Specific phobia is a common anxiety disorder, but the literature on associated brain structure alterations exhibits substantial gaps. The ENIGMA Anxiety Working Group examined brain structure differences between individuals with specific phobias and healthy control subjects as well as between the animal and blood-injection-injury (BII) subtypes of specific phobia. Additionally, the authors investigated associations of brain structure with symptom severity and age (youths vs. adults).Data sets from 31 original studies were combined to create a final sample with 1,452 participants with phobia and 2,991 healthy participants (62.7% female; ages 5-90). Imaging processing and quality control were performed using established ENIGMA protocols. Subcortical volumes as well as cortical surface area and thickness were examined in a preregistered analysis.Compared with the healthy control group, the phobia group showed mostly smaller subcortical volumes, mixed surface differences, and larger cortical thickness across a substantial number of regions. The phobia subgroups also showed differences, including, as hypothesized, larger medial orbitofrontal cortex thickness in BII phobia (N=182) compared with animal phobia (N=739). All findings were driven by adult participants; no significant results were observed in children and adolescents.Brain alterations associated with specific phobia exceeded those of other anxiety disorders in comparable analyses in extent and effect size and were not limited to reductions in brain structure. Moreover, phenomenological differences between phobia subgroups were reflected in diverging neural underpinnings, including brain areas related to fear processing and higher cognitive processes. The findings implicate brain structure alterations in specific phobia, although subcortical alterations in particular may also relate to broader internalizing psychopathology.
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| 452. |
- Hoffmann, Jean-Marc, et al.
(författare)
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Differences in Expansion Potential of Naive Chimeric Antigen Receptor T Cells from Healthy Donors and Untreated Chronic Lymphocytic Leukemia Patients
- 2018
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Ingår i: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Therapy with chimeric antigen receptor T (CART) cells for hematological malignancies has shown promising results. Effectiveness of CART cells may depend on the ratio of naive (T-N) vs. effector (T-E) T cells, TN cells being responsible for an enduring antitumor activity through maturation. Therefore, we investigated factors influencing the T-N/T-E ratio of CART cells.Materials and methods: CART cells were generated upon transduction of peripheral blood mononuclear cells with a CD19.CAR-CD28-CD137zeta third generation retroviral vector under two different stimulating culture conditions: anti-CD3/anti-CD28 antibodies adding either interleukin (IL)-7/1L-15 or IL-2. CART cells were maintained in culture for 20 days. We evaluated 24 healthy donors (HDs) and 11 patients with chronic lymphocytic leukemia (CLL) for the composition of cell subsets and produced CART cells. Phenotype and functionality were tested using flow cytometry and chromium release assays.Results: IL -7/1L-15 preferentially induced differentiation into T-N, stem cell memory (T-SCM: naive CD27+ CD95+), CD4+ and CXCR3+ CART cells, while IL-2 increased effector memory (T-EM), CD56+ and CD4+ T regulatory (T-Reg) CART cells. The net amplification of different CART subpopulations derived from HDs and untreated CLL patients was compared. Particularly the expansion of CD4+ CART(N) cells differed significantly between the two groups. For HDs, this subtype expanded >60-fold, whereas CD4+ CART(N) cells of untreated CLL patients expanded less than 10-fold. Expression of exhaustion marker programmed cell death 1 on CART(N) cells on day 10 of culture was significantly higher in patient samples compared to HD samples. As the percentage of malignant B cells was expectedly higher within patient samples, an excessive amount of B cells during culture could account for the reduced expansion potential of CART(N) cells in untreated CLL patients. Final T-N/T-E ratio stayed <0.3 despite stimulation condition for patients, whereas this ratio was >2 in samples from HDs stimulated with IL-7/1L-15, thus demonstrating efficient CART(N) expansion.Conclusion: Untreated CLL patients might constitute a challenge for long-lasting CART effects in vivo since only a low number of T-N among the CART product could be generated. Depletion of malignant B cells before starting CART production might be considered to increase the T-N/T-E ratio within the CART product.
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| 453. |
- Hoffmann, Markus, et al.
(författare)
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Camostat mesylate inhibits SARS-CoV-2 activation by TMPRSS2-related proteases and its metabolite GBPA exerts antiviral activity
- 2021
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Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 65
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Tidskriftsartikel (refereegranskat)abstract
- Background: Antivirals are needed to combat the COVID-19 pandemic, which is caused by SARS-CoV-2. The clinically-proven protease inhibitor Camostat mesylate inhibits SARS-CoV-2 infection by blocking the virus-activating host cell protease TMPRSS2. However, antiviral activity of Camostat mesylate metabolites and potential viral resistance have not been analyzed. Moreover, antiviral activity of Camostat mesylate in human lung tissue remains to be demonstrated. Methods: We used recombinant TMPRSS2, reporter particles bearing the spike protein of SARS-CoV-2 or authentic SARS-CoV-2 to assess inhibition of TMPRSS2 and viral entry, respectively, by Camostat mesylate and its metabolite GBPA. Findings: We show that several TMPRSS2-related proteases activate SARS-CoV-2 and that two, TMPRSS11D and TMPRSS13, are robustly expressed in the upper respiratory tract. However, entry mediated by these proteases was blocked by Camostat mesylate. The Camostat metabolite GBPA inhibited recombinant TMPRSS2 with reduced efficiency as compared to Camostat mesylate. In contrast, both inhibitors exhibited similar antiviral activity and this correlated with the rapid conversion of Camostat mesylate into GBPA in the presence of serum. Finally, Camostat mesylate and GBPA blocked SARS-CoV-2 spread in human lung tissue ex vivo and the related protease inhibitor Nafamostat mesylate exerted augmented antiviral activity. Interpretation: Our results suggest that SARS-CoV-2 can use TMPRSS2 and closely related proteases for spread in the upper respiratory tract and that spread in the human lung can be blocked by Camostat mesylate and its metabolite GBPA. Funding: NIH, Damon Runyon Foundation, ACS, NYCT, DFG, EU, Berlin Mathematics center MATH+, BMBF, Lower Saxony, Lundbeck Foundation, Novo Nordisk Foundation.
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| 454. |
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| 455. |
- Hofmann, B, et al.
(författare)
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Research Integrity Among PhD Students at the Faculty of Medicine: A Comparison of Three Scandinavian Universities
- 2020
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Ingår i: Journal of empirical research on human research ethics : JERHRE. - : SAGE Publications. - 1556-2654 .- 1556-2646. ; 15:4, s. 320-329
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Tidskriftsartikel (refereegranskat)abstract
- This study investigates research integrity among PhD students in health sciences at three universities in Scandinavia (Stockholm, Oslo, Odense). A questionnaire with questions on knowledge, attitudes, experiences, and behavior was distributed to PhD students and obtained a response rate of 77.7%. About 10% of the respondents agreed that research misconduct strictly defined (such as fabrication, falsification, and plagiarism, FFP) is common in their area of research, while slightly more agreed that other forms of misconduct is common. A nonnegligible segment of the respondents was willing to fabricate, falsify, or omit contradicting data if they believe that they are right in their overall conclusions. Up to one third reported to have added one or more authors unmerited. Results showed a negative correlation between “good attitudes” and self-reported misconduct and a positive correlation between how frequent respondents thought that misconduct occurs and whether they reported misconduct themselves. This reveals that existing educational and research systems partly fail to foster research integrity.
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| 456. |
- Hofmann, B, et al.
(författare)
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Scientific Dishonesty: A Survey of Doctoral Students at the Major Medical Faculties in Sweden and Norway
- 2015
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Ingår i: Journal of empirical research on human research ethics : JERHRE. - : SAGE Publications. - 1556-2654 .- 1556-2646. ; 10:4, s. 380-388
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Tidskriftsartikel (refereegranskat)abstract
- As we need knowledge about the prevalence of scientific dishonesty, this study investigates the knowledge of, experiences with, and attitudes toward various forms of scientific dishonesty among PhD students at the main medical faculties in Sweden and Norway. An anonymous questionnaire was distributed to all post-graduate research students attending basic PhD courses at the medical faculties in Stockholm and Oslo during the fall 2014. The responding doctoral students reported to know about various forms of scientific dishonesty from the literature, in their department, and for some also through their own experience. Some forms of scientific misconduct were considered to be acceptable by a significant minority. There was a high level of willingness to report misconduct but little awareness of relevant policies for scientific conduct.
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| 457. |
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| 458. |
- Hofmann, Fabian, et al.
(författare)
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Targeted therapy for metastatic renal cell carcinoma
- 2020
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Ingår i: Cochrane Database of Systematic Reviews. - : John Wiley & Sons. - 1469-493X. ; :10
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Forskningsöversikt (refereegranskat)abstract
- Background: Several comparative randomised controlled trials (RCTs) have been performed including combinations of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors since the publication of a Cochrane Review on targeted therapy for metastatic renal cell carcinoma (mRCC) in 2008. This review represents an update of that original review.Objectives: To assess the effects of targeted therapies for clear cell mRCC in patients naïve to systemic therapy.Search methods: We performed a comprehensive search with no restrictions on language or publication status. The date of the latest search was 18 June 2020.Selection criteria: We included randomised controlled trials, recruiting patients with clear cell mRCC naïve to previous systemic treatment. The index intervention was any TKI‐based targeted therapy.Data collection and analysis: Two review authors independently assessed the included studies and extracted data for the primary outcomes: progression‐free survival (PFS), overall survival (OS) and serious adverse events (SAEs); and the secondary outcomes: health‐related quality of life (QoL), response rate and minor adverse events (AEs). We performed statistical analyses using a random‐effects model and rated the certainty of evidence according to the GRADE approach.Main results: We included 18 RCTs reporting on 11,590 participants randomised across 18 comparisons. This abstract focuses on the primary outcomes of select comparisons.
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| 459. |
- Hofmann, Fabian, et al.
(författare)
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Targeted therapy for metastatic renal cell carcinoma
- 2017
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Ingår i: Cochrane Database of Systematic Reviews. - : John Wiley & Sons. - 1469-493X. ; 2017:9
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Tidskriftsartikel (refereegranskat)abstract
- This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To compare the effects of targeted agents in the systemic therapy of people with metastatic renal cell carcinoma.
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| 460. |
- Hofmann, H., et al.
(författare)
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Potential of nanosized ceramic powder for functional applications
- 1997
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Ingår i: Ceramic Engineering and Science Proceedings. ; , s. 687-694
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Konferensbidrag (refereegranskat)abstract
- Nanophase ceramic particles are building-blocks for the formation of nanostructured ceramics and are important in a composite for functional applications. Different synthesis methods for nanosized ceramics were developed. Depending on the method and chemical composition, powders which are agglomerates of nanosized primary particles exist. These primary particles show very small grain size distribution.
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