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Author Correction: A multi-modal single-cell and spatial expression map of metastatic breast cancer biopsies across clinicopathological features
No full textTGFα controls checkpoints in CNS resident and infiltrating immune cells to promote resolution of inflammation
No full textAfter acute lesions in the central nervous system (CNS), the interaction of microglia, astrocytes, and infiltrating immune cells decides over their resolution or chronification. However, this CNS-intrinsic cross-talk is poorly characterized. Analyzing cerebrospinal fluid (CSF) samples of Multiple Sclerosis (MS) patients as well as CNS samples of female mice with experimental autoimmune encephalomyelitis (EAE), the animal model of MS, we identify microglia-derived TGFα as key factor driving recovery. Through mechanistic in vitro studies, in vivo treatment paradigms, scRNA sequencing, CRISPR-Cas9 genetic perturbation models and MRI in the EAE model, we show that together with other glial and non-glial cells, microglia secrete TGFα in a highly regulated temporospatial manner in EAE. Here, TGFα contributes to recovery by decreasing infiltrating T cells, pro-inflammatory myeloid cells, oligodendrocyte loss, demyelination, axonal damage and neuron loss even at late disease stages. In a therapeutic approach in EAE, blood-brain barrier penetrating intranasal application of TGFα attenuates pro-inflammatory signaling in astrocytes and CNS infiltrating immune cells while promoting neuronal survival and lesion resolution. Together, microglia-derived TGFα is an important mediator of glial-immune crosstalk, highlighting its therapeutic potential in resolving acute CNS inflammation
Immunization acceptance after broad recommendation for RSV prophylaxis: Results from a cross-sectional study in Germany
No full textThis study assessed parental acceptance of nirsevimab, a new RSV prophylaxis recommended for newborns in Germany. A cross-sectional survey was conducted at two German university hospitals during the 2024-2025 RSV season, with 519 parents completing questionnaires about their attitudes toward this immunization. Results showed moderate acceptance, with only 40.5 % of parents agreeing to nirsevimab administration, while 31.2 % were undecided and 14.3 % declined. Parents with higher education levels, greater RSV concerns, and those feeling well-informed were significantly more likely to accept the prophylaxis. The primary reasons for hesitancy included insufficient information (32.9 %), safety concerns (31.6 %), and reluctance to give injections to newborns (22.4 %). The study reveals that nirsevimab acceptance among German parents was lower than in other European countries, highlighting the need for enhanced educational campaigns. Targeted communication strategies emphasizing safety and efficacy, particularly for families with lower educational backgrounds, could improve acceptance rates and reduce infant RSV-related morbidity
Investigating the Molecular Composition of Neuronal Subcompartments Using Proximity Labeling
No full textDissecting heterogeneity in cortical thickness abnormalities in major depressive disorder: a large-scale ENIGMA MDD normative modelling study
No full textAbstract Importance Major depressive disorder (MDD) is highly heterogeneous, with marked individual differences in clinical presentation and neurobiology, which may obscure identification of structural brain abnormalities in MDD. To explore this, we used normative modeling to index regional patterns of variability in cortical thickness (CT) across individual patients. Objective To use normative modeling in a large dataset from the ENIGMA MDD consortium to obtain individualised CT deviations from the norm (relative to age, sex and site) and examine the relationship between these deviations and clinical characteristics. Design, setting, and participants A normative model adjusting for age, sex and site effects was trained on 35 CT measures from FreeSurfer parcellation of 3,181 healthy controls (HC) from 34 sites (40 scanners). Individualised z-score deviations from this norm for each CT measure were calculated for a test set of 2,119 HC and 3,645 individuals with MDD. For each individual, each CT z-score was classified as being within the normal range (95% of individuals) or within the extreme range (2.5% of individuals with the thinnest or thickest cortices). Main outcome measures Z-score deviations of CT measures of MDD individuals as estimated from a normative model based on HC. Results Z-score distributions of CT measures were largely overlapping between MDD and HC (minimum 92%, range 92-98%), with overall thinner cortices in MDD. 34.5% of MDD individuals, and 30% of HC individuals, showed an extreme deviation in at least one region, and these deviations were widely distributed across the brain. There was high heterogeneity in the spatial location of CT deviations across individuals with MDD: a maximum of 12% of individuals with MDD showed an extreme deviation in the same location. Extreme negative CT deviations were associated with having an earlier onset of depression and more severe depressive symptoms in the MDD group, and with higher BMI across MDD and HC groups. Extreme positive deviations were associated with being remitted, of not taking antidepressants and less severe symptoms. Conclusions and relevance Our study illustrates a large heterogeneity in the spatial location of CT abnormalities across patients with MDD and confirms a substantial overlap of CT measures with HC. We also demonstrate that individualised extreme deviations can identify protective factors and individuals with a more severe clinical picture. Key points Question Can z-scores derived from normative modelling shed light on the heterogeneous group-level findings of cortical thickness abnormalities in major depression and what characterises individuals at the extreme ends of cortical thickness abnormalities? Finding We confirmed a large overlap in z-score distributions between depressed individuals and healthy controls and a heterogeneous spatial distribution of extreme z-deviations across brain regions across individual patients. Lower z-scores for cortical thickness were related to more severe clinical characteristics. Meaning Our findings confirm the heterogeneity in individual variation in the location and extent of CT abnormalities across patients with MDD and stress the importance of individualised predictions when examining cortical thickness abnormalities
Brain Aging in Specific Phobia: An ENIGMA-Anxiety Mega-Analysis
No full textIntroduction Specific phobia (SPH) is a prevalent anxiety disorder and may involve advanced biological aging. However, brain age research in psychiatry has primarily examined mood and psychotic disorders. This mega-analysis investigated brain aging in SPH participants within the ENIGMA-Anxiety Working Group. Methods 3D brain s tructural MRI scans from 17 international samples (600 SPH individuals, of whom 504 formally diagnosed and 96 questionnaire-based cases; 1,134 controls; age range: 22-75 years) were processed with FreeSurfer. Brain age was estimated from 77 subcortical and cortical regions with a publicly available ENIGMA brain age model. The brain-predicted age difference (brain-PAD) was calculated as brain age minus chronological age. Linear mixed-effect models examined group differences in brain-PAD and moderation by age. Results No significant group difference in brain-PAD manifested ( β diagnosis (SE)=0.37 years (0.43), p =0.39). A negative diagnosis-by-age interaction was identified, which was most pronounced in formally diagnosed SPH ( β diagnosis-by-age =-0.08 (0.03), pFDR =0.02). This interaction remained significant when excluding participants with anxiety comorbidities, depressive comorbidities, and medication use. Post-hoc analyses revealed a group difference for formal SPH diagnosis in younger participants (22-35 years; β diagnosis =1.20 (0.60), p <0.05, mixed-effects d (95% confidence interval)=0.14 (0.00-0.28)), but not older participants (36-75 years; β diagnosis =0.07 (0.65), p =0.91). Conclusions Brain aging did not relate to SPH in the full sample. However, a diagnosis-by-age interaction was observed across analyses, and was strongest in formally diagnosed SPH. Post-hoc analyses showed a subtle advanced brain aging in young adults with formally diagnosed SPH. Taken together, these findings indicate the importance of clinical severity, impairment and persistence, and may suggest a slightly earlier end to maturational processes or subtle decline of brain structure in SPH
Search for Dark Matter Produced in Association with a Dark Higgs Boson in the b b ¯ Final State Using p p Collisions at s = 13 TeV with the ATLAS Detector
No full textA search is performed for dark matter particles produced in association with a resonantly produced pair of b -quarks with 30 < m b b < 150 GeV using 140 fb − 1 of proton-proton collisions at a center-of-mass energy of 13 TeV recorded by the ATLAS detector at the LHC. This signature is expected in extensions of the standard model predicting the production of dark matter particles, in particular those containing a dark Higgs boson s that decays into b b ¯ . The highly boosted s → b b ¯ topology is reconstructed using jet reclustering and a new identification algorithm. This search places stringent constraints across regions of the dark Higgs model parameter space that satisfy the observed relic density, excluding dark Higgs bosons with masses between 30 and 150 GeV in benchmark scenarios with Z ′ mediator masses up to 4.8 TeV at 95% confidence level. © 2025 CERN, for the ATLAS Collaboration 2025 CERNCERN http://dx.doi.org/10.13039/100012470TRIUMF http://dx.doi.org/10.13039/100012419Institut National de Physique Nucléaire et de Physique des Particules http://dx.doi.org/10.13039/501100012441Karlsruhe Institute of Technology http://dx.doi.org/10.13039/100009133Instituto Nazionale di Fisica Nucleare http://dx.doi.org/10.13039/501100004007Brookhaven National Laboratory http://dx.doi.org/10.13039/100006231Agencia Nacional de Promoción Científica y Tecnológica http://dx.doi.org/10.13039/501100003074Australian Research Council http://dx.doi.org/10.13039/501100000923Bundesministerium für Wissenschaft, Forschung und Wirtschaft http://dx.doi.org/10.13039/501100003413Austrian Science Fund http://dx.doi.org/10.13039/501100002428Arizona-Nevada Academy of Science http://dx.doi.org/10.13039/100011590Conselho Nacional de Desenvolvimento Científico e Tecnológico http://dx.doi.org/10.13039/501100003593Fundação de Amparo à Pesquisa do Estado de São Paulo http://dx.doi.org/10.13039/501100001807Natural Sciences and Engineering Research Council of Canada http://dx.doi.org/10.13039/501100000038National Research Council Canada http://dx.doi.org/10.13039/501100000046Canada Foundation for Innovation http://dx.doi.org/10.13039/501100000196Agencia Nacional de Investigación y Desarrollo http://dx.doi.org/10.13039/501100020884Chinese Academy of Sciences http://dx.doi.org/10.13039/501100002367Ministry of Science and Technology of the People’s Republic of China http://dx.doi.org/10.13039/501100002855National Natural Science Foundation of China http://dx.doi.org/10.13039/501100001809Ministerstvo Školství, Mládeže a T?lovýchovy http://dx.doi.org/10.13039/501100001823Danmarks Grundforskningsfond http://dx.doi.org/10.13039/501100001732Centre National de la Recherche Scientifique http://dx.doi.org/10.13039/501100004794Commissariat à l’Énergie Atomique et aux Énergies Alternatives http://dx.doi.org/10.13039/501100006489Bundesministerium für Bildung und Forschung http://dx.doi.org/10.13039/501100002347Helmholtz-Gemeinschaft http://dx.doi.org/10.13039/501100001656Max-Planck-Gesellschaft http://dx.doi.org/10.13039/501100004189Food and Health Bureau http://dx.doi.org/10.13039/501100005407Israel Science Foundation http://dx.doi.org/10.13039/501100003977Ministry of Education, Culture, Sports, Science and Technology http://dx.doi.org/10.13039/501100001700Japan Society for the Promotion of Science http://dx.doi.org/10.13039/501100001691Centre National pour la Recherche Scientifique et Technique http://dx.doi.org/10.13039/501100006319Nederlandse Organisatie voor Wetenschappelijk Onderzoek http://dx.doi.org/10.13039/501100003246MNiSW http://dx.doi.org/10.13039/501100004569Fundação para a Ciência e a Tecnologia http://dx.doi.org/10.13039/501100001871Institutul de Fizic? Atomic? http://dx.doi.org/10.13039/501100019278Javna Agencija za Raziskovalno Dejavnost RS http://dx.doi.org/10.13039/501100004329National Research Foundation http://dx.doi.org/10.13039/501100001321Ministerio de Ciencia e Innovación http://dx.doi.org/10.13039/501100004837Vetenskapsrådet http://dx.doi.org/10.13039/501100004359Knut och Alice Wallenbergs Stiftelse http://dx.doi.org/10.13039/501100004063National Science Foundation http://dx.doi.org/10.13039/100000001Türkiye Enerji, Nükleer ve Maden Ara?t?rma Kurumu http://dx.doi.org/10.13039/100020381Science and Technology Facilities Council http://dx.doi.org/10.13039/501100000271U.S. Department of Energy http://dx.doi.org/10.13039/100000015British Columbia Knowledge Development Fund http://dx.doi.org/10.13039/501100007711Canarie http://dx.doi.org/10.13039/100008313H2020 European Research Council http://dx.doi.org/10.13039/100010663European Regional Development Fund http://dx.doi.org/10.13039/501100008530Horizon 2020 Framework Programme http://dx.doi.org/10.13039/100010661Ministero dell’Istruzione, dell’Università e della Ricerca http://dx.doi.org/10.13039/501100003407H2020 Marie Skłodowska-Curie Actions http://dx.doi.org/10.13039/100010665European Commission http://dx.doi.org/10.13039/501100000780Agence Nationale de la Recherche http://dx.doi.org/10.13039/501100001665Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659European Social Fund http://dx.doi.org/10.13039/501100004895United States-Israel Binational Science Foundation http://dx.doi.org/10.13039/501100001742Narodowe Centrum Nauki http://dx.doi.org/10.13039/501100004281Narodowa Agencja Wymiany Akademickiej http://dx.doi.org/10.13039/501100014434’la Caixa’ Foundation http://dx.doi.org/10.13039/100010434Centres de Recerca de Catalunya http://dx.doi.org/10.13039/100015439Generalitat de Catalunya http://dx.doi.org/10.13039/501100002809Generalitat Valenciana http://dx.doi.org/10.13039/501100003359Göran Gustafssons Stiftelser http://dx.doi.org/10.13039/100016408Royal Society http://dx.doi.org/10.13039/501100000288Leverhulme Trust http://dx.doi.org/10.13039/501100000275Fondo Nacional de Desarrollo Científico y Tecnológico http://dx.doi.org/10.13039/501100002850Grantová Agentura České Republiky http://dx.doi.org/10.13039/501100001824Ministry of Education, Youth and Science http://dx.doi.org/10.13039/501100003335Baden-Württemberg Stiftung http://dx.doi.org/10.13039/100008316Norges Forskningsråd http://dx.doi.org/10.13039/501100005416Federación Española de Enfermedades Raras http://dx.doi.org/10.13039/501100002924Carl Tryggers Stiftelse för Vetenskaplig Forskning http://dx.doi.org/10.13039/501100002805Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung http://dx.doi.org/10.13039/501100001711Neubauer Family Foundation http://dx.doi.org/10.13039/100019099NDGF 100024502NL-T1PICRALYerPhIMinciencias 100022965DNSRCSRNSFGGSRI 501100003448RGCThe Nella and Leon Benoziyo Center for High Energy Physics, Weizmann Institute of ScienceRCNMESTDMSSRMIZŠSERICantons of Bern and GenevaMOSTCRCDRACICSC-NextGenerationEUInvestissements d’ Avenir LabexAvH Foundation 100005156NSRFMINERVAItalian Center for High Performance ComputingBig Data and Quantum ComputingICSC 10002304
Anamnese, klinische Merkmale, Therapie und patientenberichtete Ergebnisse bei Lichen ruber mucosae: Eine Querschnittsstudie
No full textZusammenfassung Hintergrund Der Lichen ruber mucosae (LRM) ist eine chronische entzündliche Erkrankung. Der Weg des Patienten mit der Krankheit kann schwierig sein, da die Diagnosestellung und Therapie eine Herausforderung darstellen. Patienten und Methodik In dieser Querschnittsstudie wurden bei insgesamt 72 Patienten mit LRM, die zwischen 02/2022 und 07/2023 in den dermatologischen Abteilungen von sechs deutschen Universitätskliniken behandelt wurden, eine Vielzahl von Charakteristika zum Krankheitsverlauf erfasst und ausgewertet. Ergebnisse Zwischen dem Auftreten der Symptome und der Diagnosestellung lagen im Durchschnitt 18,1 Monate. Bis zur korrekten Diagnosestellung wurden durchschnittlich 3,1 verschiedene Ärzte der gleichen oder anderer Fachrichtungen konsultiert. 28,1% der Patienten hatten auch eine Hautbeteiligung. Therapeutisch erhielten 68% der Patienten mindestens ein systemisches Medikament. Sowohl topische (90%, 65/72) als auch systemische (oral, 50%, 36/72; intravenös, 33%, 24/72) Glukokortikoide wurden am häufigsten eingesetzt. Systemische Medikamente wurden am häufigsten wegen Unwirksamkeit abgesetzt (46%, 50/110). Die Zufriedenheit mit der Behandlung war bei intravenösen und topischen Glukokortikoiden am höchsten (mittlere bis hohe Zufriedenheit: 59% bzw. 36%) und bei Retinoiden mit 8% am niedrigsten. Schlussfolgerungen Die Ergebnisse dieser Studie deuten darauf hin, dass das diagnostische Bewusstsein der Ärzte möglicherweise unzureichend ist und dass ein Bedarf an wirksamen systemischen Therapien besteht