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Article: Musical experience influences socio-emotional functioning in behavioural variant frontotemporal dementia.

Van't Hooft, Jochum J / Benhamou, Elia / Albero Herreros, Claudia / Jiang, Jessica / Levett, Benjamin / Core, Lucy B / Requena-Komuro, Mai-Carmen / Hardy, Chris J D / Tijms, Betty M / Pijnenburg, Yolande A L / Warren, Jason D

Frontiers in neurology

2024 Volume 15, Page(s) 1341661

Abstract: Objectives: On phenotypic and neuroanatomical grounds, music exposure might potentially affect the clinical expression of behavioural variant frontotemporal dementia (bvFTD). However, this has not been clarified.: Methods: 14 consecutive patients ... ...

Abstract	Objectives: On phenotypic and neuroanatomical grounds, music exposure might potentially affect the clinical expression of behavioural variant frontotemporal dementia (bvFTD). However, this has not been clarified. Methods: 14 consecutive patients with bvFTD fulfilling consensus diagnostic criteria were recruited via a specialist cognitive clinic. Earlier life musical experience, current musical listening habits and general socio-emotional behaviours were scored using a bespoke semi-quantitative musical survey and standardised functional scales, completed with the assistance of patients' primary caregivers. Associations of musical scores with behavioural scales were assessed using a linear regression model adjusted for age, sex, educational attainment and level of executive and general cognitive impairment. Results: Greater earlier life musical experience was associated with significantly lower Cambridge Behavioural Inventory (Revised) scores (β ± SE = -17.2 ± 5.2; Discussion: Musical experience in earlier life and potentially ongoing regular music listening may ameliorate socio-emotional functioning in bvFTD. Future work in larger cohorts is required to substantiate the robustness of this association, establish its mechanism and evaluate its clinical potential.
Language	English
Publishing date	2024-01-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2024.1341661
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Article ; Online: Clutch mechanism of chemomechanical coupling in a DNA resecting motor nuclease.

Unciuleac, Mihaela-Carmen / Meir, Aviv / Xue, Chaoyou / Warren, Garrett M / Greene, Eric C / Shuman, Stewart

Proceedings of the National Academy of Sciences of the United States of America

2021 Volume 118, Issue 11

Abstract: Mycobacterial AdnAB is a heterodimeric helicase-nuclease that initiates homologous recombination by resecting DNA double-strand breaks (DSBs). The N-terminal motor domain of the AdnB subunit hydrolyzes ATP to drive rapid and processive 3' to 5' ... ...

Abstract	Mycobacterial AdnAB is a heterodimeric helicase-nuclease that initiates homologous recombination by resecting DNA double-strand breaks (DSBs). The N-terminal motor domain of the AdnB subunit hydrolyzes ATP to drive rapid and processive 3' to 5' translocation of AdnAB on the tracking DNA strand. ATP hydrolysis is mechanically productive when oscillating protein domain motions synchronized with the ATPase cycle propel the DNA tracking strand forward by a single-nucleotide step, in what is thought to entail a pawl-and-ratchet-like fashion. By gauging the effects of alanine mutations of the 16 amino acids at the AdnB-DNA interface on DNA-dependent ATP hydrolysis, DNA translocation, and DSB resection in ensemble and single-molecule assays, we gained key insights into which DNA contacts couple ATP hydrolysis to motor activity. The results implicate AdnB Trp325, which intercalates into the tracking strand and stacks on a nucleobase, as the singular essential constituent of the ratchet pawl, without which ATP hydrolysis on ssDNA is mechanically futile. Loss of Thr663 and Thr118 contacts with tracking strand phosphates and of His665 with a nucleobase drastically slows the AdnAB motor during DSB resection. Our findings for AdnAB prompt us to analogize its mechanism to that of an automobile clutch.
MeSH term(s)	Adenosine Triphosphate/metabolism ; Bacterial Proteins/chemistry ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Cryoelectron Microscopy ; DNA Breaks, Double-Stranded ; DNA Helicases/chemistry ; DNA Helicases/genetics ; DNA Helicases/metabolism ; DNA Repair ; DNA, Bacterial/metabolism ; DNA, Single-Stranded/metabolism ; Endodeoxyribonucleases/chemistry ; Endodeoxyribonucleases/genetics ; Endodeoxyribonucleases/metabolism ; Hydrolysis ; Mutation ; Mycobacterium/enzymology ; Mycobacterium/genetics ; Protein Binding ; Protein Domains
Chemical Substances	Bacterial Proteins ; DNA, Bacterial ; DNA, Single-Stranded ; Adenosine Triphosphate (8L70Q75FXE) ; Endodeoxyribonucleases (EC 3.1.-) ; DNA Helicases (EC 3.6.4.-)
Language	English
Publishing date	2021-03-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2023955118
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Article ; Online: Assessing depression recurrence, cognitive burden, and neurobiological homeostasis in late life: Design and rationale of the REMBRANDT Study.

Taylor, Warren D / Ajilore, Olusola / Karim, Helmet T / Butters, Meryl A / Krafty, Robert / Boyd, Brian D / Banihashemi, Layla / Szymkowicz, Sarah M / Ryan, Claire / Hassenstab, Jason / Landman, Bennett A / Andreescu, Carmen

Journal of mood and anxiety disorders

2023 Volume 5

Abstract: Background: Late-life depression is characterized by disability, cognitive impairment and decline, and a high risk of recurrence following remission. Aside from past psychiatric history, prognostic neurobiological and clinical factors influencing ... ...

Abstract	Background: Late-life depression is characterized by disability, cognitive impairment and decline, and a high risk of recurrence following remission. Aside from past psychiatric history, prognostic neurobiological and clinical factors influencing recurrence risk are unclear. Moreover, it is unclear if cognitive impairment predisposes to recurrence, or whether recurrent episodes may accelerate brain aging and cognitive decline. The purpose of the REMBRANDT study (Recurrence markers, cognitive burden, and neurobiological homeostasis in late-life depression) is to better elucidate these relationships and identify phenotypic, cognitive, environmental, and neurobiological factors contributing to and predictive of depression recurrence. Methods: Across three sites, REMBRANDT will enroll 300 depressed elders who will receive antidepressant treatment. The goal is to enroll 210 remitted depressed participants and 75 participants with no mental health history into a two-year longitudinal phase focusing on depression recurrence. Participants are evaluated every 2 months with deeper assessments occurring every 8 months, including structural and functional neuroimaging, environmental stress assessments, deep symptom phenotyping, and two weeks of 'burst' ecological momentary assessments to elucidate variability in symptoms and cognitive performance. A broad neuropsychological test battery is completed at the beginning and end of the longitudinal study. Significance: REMBRANDT will improve our understanding of how alterations in neural circuits and cognition that persist during remission contribute to depression recurrence vulnerability. It will also elucidate how these processes may contribute to cognitive impairment and decline. This project will obtain deep phenotypic data that will help identify vulnerability and resilience factors that can help stratify individual clinical risk.
Language	English
Publishing date	2023-11-04
Publishing country	United States
Document type	Journal Article
ISSN	2950-0044
ISSN (online)	2950-0044
DOI	10.1016/j.xjmad.2023.100038
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Article ; Online: Podosome rosettes precede vascular sprouts in tumour angiogenesis.

Warren, Carmen M / Iruela-Arispe, M Luisa

Nature cell biology

2014 Volume 16, Issue 10, Page(s) 928–930

Abstract: Expansion of a vascular network requires breaking through the basement membrane, a highly crosslinked barrier that tightly adheres to mature vessels. Angiogenic endothelial cells are now shown to form podosome rosettes that are able to focally degrade ... ...

Abstract	Expansion of a vascular network requires breaking through the basement membrane, a highly crosslinked barrier that tightly adheres to mature vessels. Angiogenic endothelial cells are now shown to form podosome rosettes that are able to focally degrade the extracellular matrix, prior to vascular sprouting in tumour angiogenesis.
MeSH term(s)	Basement Membrane/metabolism ; Cell Membrane Structures/metabolism ; Cell Membrane Structures/physiology ; Endothelial Cells/metabolism ; Endothelial Cells/physiology ; Extracellular Matrix/metabolism ; Humans ; Integrin alpha6beta1/metabolism ; Models, Biological ; Neoplasms/blood supply ; Neoplasms/metabolism ; Neoplasms/physiopathology ; Neovascularization, Pathologic/metabolism ; Neovascularization, Pathologic/physiopathology
Chemical Substances	Integrin alpha6beta1
Language	English
Publishing date	2014-10-01
Publishing country	England
Document type	News
ZDB-ID	1474722-4
ISSN	1476-4679 ; 1465-7392
ISSN (online)	1476-4679
ISSN	1465-7392
DOI	10.1038/ncb3044
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Zs.A 5169: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 12: Show issues

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Article ; Online: Product Attributes of CAR T-cell Therapy Differentially Associate with Efficacy and Toxicity in Second-line Large B-cell Lymphoma (ZUMA-7).

Blood cancer discovery

2023 Volume 5, Issue 1, Page(s) 21–33

Abstract: Treatment resistance and toxicities remain a risk following chimeric antigen receptor (CAR) T-cell therapy. Herein, we report pharmacokinetics, pharmacodynamics, and product and apheresis attributes associated with outcomes among patients with relapsed/ ... ...

Abstract	Treatment resistance and toxicities remain a risk following chimeric antigen receptor (CAR) T-cell therapy. Herein, we report pharmacokinetics, pharmacodynamics, and product and apheresis attributes associated with outcomes among patients with relapsed/refractory large B-cell lymphoma (LBCL) treated with axicabtagene ciloleucel (axi-cel) in ZUMA-7. Axi-cel peak expansion associated with clinical response and toxicity, but not response durability. In apheresis material and final product, a naive T-cell phenotype (CCR7+CD45RA+) expressing CD27 and CD28 associated with improved response durability, event-free survival, progression-free survival, and a lower number of prior therapies. This phenotype was not associated with high-grade cytokine release syndrome (CRS) or neurologic events. Higher baseline and postinfusion levels of serum inflammatory markers associated with differentiated/effector products, reduced efficacy, and increased CRS and neurologic events, thus suggesting targets for intervention. These data support better outcomes with earlier CAR T-cell intervention and may improve patient care by informing on predictive biomarkers and development of next-generation products. Significance: In ZUMA-7, the largest randomized CAR T-cell trial in LBCL, a naive T-cell product phenotype (CCR7+CD45RA+) expressing CD27 and CD28 associated with improved efficacy, decreased toxicity, and a lower number of prior therapies, supporting earlier intervention with CAR T-cell therapy. In addition, targets for improvement of therapeutic index are proposed. This article is featured in Selected Articles from This Issue, p. 4.
MeSH term(s)	Humans ; Immunotherapy, Adoptive/adverse effects ; CD28 Antigens ; Receptors, CCR7 ; Lymphoma, Large B-Cell, Diffuse/therapy ; Research Personnel ; Cytokine Release Syndrome ; Leukocyte Common Antigens
Chemical Substances	CD28 Antigens ; Receptors, CCR7 ; Leukocyte Common Antigens (EC 3.1.3.48)
Language	English
Publishing date	2023-11-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	3028898-8
ISSN	2643-3249 ; 2643-3230
ISSN (online)	2643-3249
ISSN	2643-3230
DOI	10.1158/2643-3230.BCD-23-0112
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Article ; Online: Decoding expectation and surprise in dementia: the paradigm of music.

Benhamou, Elia / Zhao, Sijia / Sivasathiaseelan, Harri / Johnson, Jeremy C S / Requena-Komuro, Maï-Carmen / Bond, Rebecca L / van Leeuwen, Janneke E P / Russell, Lucy L / Greaves, Caroline V / Nelson, Annabel / Nicholas, Jennifer M / Hardy, Chris J D / Rohrer, Jonathan D / Warren, Jason D

Brain communications

2021 Volume 3, Issue 3, Page(s) fcab173

Abstract: Making predictions about the world and responding appropriately to unexpected events are essential functions of the healthy brain. In neurodegenerative disorders, such as frontotemporal dementia and Alzheimer's disease, impaired processing of 'surprise' ... ...

Abstract	Making predictions about the world and responding appropriately to unexpected events are essential functions of the healthy brain. In neurodegenerative disorders, such as frontotemporal dementia and Alzheimer's disease, impaired processing of 'surprise' may underpin a diverse array of symptoms, particularly abnormalities of social and emotional behaviour, but is challenging to characterize. Here, we addressed this issue using a novel paradigm: music. We studied 62 patients (24 female; aged 53-88) representing major syndromes of frontotemporal dementia (behavioural variant, semantic variant primary progressive aphasia, non-fluent-agrammatic variant primary progressive aphasia) and typical amnestic Alzheimer's disease, in relation to 33 healthy controls (18 female; aged 54-78). Participants heard famous melodies containing no deviants or one of three types of deviant note-acoustic (white-noise burst), syntactic (key-violating pitch change) or semantic (key-preserving pitch change). Using a regression model that took elementary perceptual, executive and musical competence into account, we assessed accuracy detecting melodic deviants and simultaneously recorded pupillary responses and related these to deviant surprise value (information-content) and carrier melody predictability (entropy), calculated using an unsupervised machine learning model of music. Neuroanatomical associations of deviant detection accuracy and coupling of detection to deviant surprise value were assessed using voxel-based morphometry of patients' brain MRI. Whereas Alzheimer's disease was associated with normal deviant detection accuracy, behavioural and semantic variant frontotemporal dementia syndromes were associated with strikingly similar profiles of impaired syntactic and semantic deviant detection accuracy and impaired behavioural and autonomic sensitivity to deviant information-content (all
Language	English
Publishing date	2021-08-10
Publishing country	England
Document type	Journal Article
ISSN	2632-1297
ISSN (online)	2632-1297
DOI	10.1093/braincomms/fcab173
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Article ; Online: Damaging Alleles Affecting Multiple CARD14 Domains Are Associated with Palmoplantar Pustulosis.

The Journal of investigative dermatology

2022 Volume 143, Issue 3, Page(s) 504–508.e5

MeSH term(s)	Humans ; Alleles ; Psoriasis/genetics ; Exanthema ; Guanylate Cyclase ; Membrane Proteins ; CARD Signaling Adaptor Proteins
Chemical Substances	CARD14 protein, human (EC 4.6.1.-) ; Guanylate Cyclase (EC 4.6.1.2) ; Membrane Proteins ; CARD Signaling Adaptor Proteins
Language	English
Publishing date	2022-09-27
Publishing country	United States
Document type	Research Support, Non-U.S. Gov't ; Letter
ZDB-ID	80136-7
ISSN	1523-1747 ; 0022-202X
ISSN (online)	1523-1747
ISSN	0022-202X
DOI	10.1016/j.jid.2022.07.031
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Article: Altered Time Awareness in Dementia.

Requena-Komuro, Maï-Carmen / Marshall, Charles R / Bond, Rebecca L / Russell, Lucy L / Greaves, Caroline / Moore, Katrina M / Agustus, Jennifer L / Benhamou, Elia / Sivasathiaseelan, Harri / Hardy, Chris J D / Rohrer, Jonathan D / Warren, Jason D

Frontiers in neurology

2020 Volume 11, Page(s) 291

Abstract: Our awareness of time, specifically of longer intervals spanning hours, days, months, and years, is critical for ensuring our sense of self-continuity. Disrupted time awareness over such intervals is a clinical feature in a number of frontotemporal ... ...

Abstract	Our awareness of time, specifically of longer intervals spanning hours, days, months, and years, is critical for ensuring our sense of self-continuity. Disrupted time awareness over such intervals is a clinical feature in a number of frontotemporal dementia syndromes and Alzheimer's disease, but has not been studied and compared systematically in these diseases. We used a semi-structured caregiver survey to capture time-related behavioral alterations in 71 patients representing all major sporadic and genetic syndromes of frontotemporal dementia, in comparison to 28 patients with typical Alzheimer's disease and nine with logopenic aphasia, and 32 healthy older individuals. Survey items pertained to apparent difficulties ordering past personal events or estimating time intervals between events, temporal rigidity and clockwatching, and propensity to relive past events. We used a logistic regression model including diagnosis, age, gender, and disease severity as regressors to compare the proportions of individuals exhibiting each temporal awareness symptom between diagnostic groups. Gray matter associations of altered time awareness were assessed using voxel-based morphometry. All patient groups were significantly more prone to exhibit temporal awareness symptoms than healthy older individuals. Clinical syndromic signatures were identified. While patients with typical and logopenic Alzheimer's disease most frequently exhibited disturbed event ordering or interval estimation, patients with semantic dementia were most prone to temporal rigidity and clockwatching and those with behavioral variant frontotemporal dementia commonly exhibited all these temporal symptoms as well as a propensity to relive past events. On voxel-based morphometry, the tendency to relive past events was associated with relative preservation of a distributed left-sided temporo-parietal gray matter network including hippocampus. These findings reveal a rich and complex picture of disturbed temporal awareness in major dementia syndromes, with stratification of frontotemporal dementia syndromes from Alzheimer's disease. This is the first study to assess symptoms of altered temporal awareness across frontotemporal dementia syndromes and provides a motivation for future work directed to the development of validated clinical questionnaires, analysis of underlying neurobiological mechanisms and design of interventions.
Language	English
Publishing date	2020-04-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2020.00291
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Article ; Online: Altered phobic reactions in frontotemporal dementia: A behavioural and neuroanatomical analysis.

Jimenez, Daniel A / Bond, Rebecca L / Requena-Komuro, Mai-Carmen / Sivasathiaseelan, Harri / Marshall, Charles R / Russell, Lucy L / Greaves, Caroline / Moore, Katrina M / Woollacott, Ione Oc / Shafei, Rachelle / Hardy, Chris Jd / Rohrer, Jonathan D / Warren, Jason D

Cortex; a journal devoted to the study of the nervous system and behavior

2020 Volume 130, Page(s) 100–110

Abstract: Introduction: Abnormal behavioural and physiological reactivity to emotional stimuli is a hallmark of frontotemporal dementia (FTD), particularly the behavioural variant (bvFTD). As part of this repertoire, altered phobic responses have been reported in ...

Abstract	Introduction: Abnormal behavioural and physiological reactivity to emotional stimuli is a hallmark of frontotemporal dementia (FTD), particularly the behavioural variant (bvFTD). As part of this repertoire, altered phobic responses have been reported in some patients with FTD but are poorly characterised. Methods: We collected data (based on caregiver reports) concerning the prevalence and nature of any behavioural changes related to specific phobias in a cohort of patients representing canonical syndromes of FTD and Alzheimer's disease (AD), relative to healthy older controls. Neuroanatomical correlates of altered phobic reactivity were assessed using voxel-based morphometry. Results: 46 patients with bvFTD, 20 with semantic variant primary progressive aphasia, 25 with non-fluent variant primary progressive aphasia, 29 with AD and 55 healthy age-matched individuals participated. Changes in specific phobia were significantly more prevalent in the combined FTD cohort (15.4% of cases) and in the bvFTD group (17.4%) compared both to healthy controls (3.6%) and patients with AD (3.5%). Attenuation of phobic reactivity was reported for individuals in all participant groups, however new phobias developed only in the FTD cohort. Altered phobic reactivity was significantly associated with relative preservation of grey matter in left posterior middle temporal gyrus, right temporo-occipital junction and right anterior cingulate gyrus, brain regions previously implicated in contextual decoding, salience processing and reward valuation. Conclusion: Altered phobic reactivity is a relatively common issue in patients with FTD, particularly bvFTD. This novel paradigm of strong fear experience has broad implications: clinically, for diagnosis and patient well-being; and neurobiologically, for our understanding of the pathophysiology of aversive sensory signal processing in FTD and the neural mechanisms of fear more generally.
MeSH term(s)	Aphasia, Primary Progressive ; Brain/diagnostic imaging ; Frontotemporal Dementia/diagnostic imaging ; Gray Matter ; Humans ; Magnetic Resonance Imaging
Language	English
Publishing date	2020-06-14
Publishing country	Italy
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	280622-8
ISSN	1973-8102 ; 0010-9452
ISSN (online)	1973-8102
ISSN	0010-9452
DOI	10.1016/j.cortex.2020.05.016
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Zs.A 687: Show issues

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Article: The 2022 ENCR Recommendations on recording and reporting of urothelial tumours of the urinary tract.

Galceran, Jaume / Parada, David / Eden, Michael / Tumino, Rosario / Warren, Anne Yvonne / Martos, Carmen / Neamtiu, Luciana / Visser, Otto / Daubisse-Marliac, Laetitia

Frontiers in oncology

2022 Volume 12, Page(s) 1046239

Abstract: An updated European Network of Cancer registries (ENCR) Recommendations on Recording and Reporting of Urothelial Tumours of the Urinary Tract had been published in 2022. After the publication by the ENCR of the "Recommendations for coding bladder cancers" ...

Abstract	An updated European Network of Cancer registries (ENCR) Recommendations on Recording and Reporting of Urothelial Tumours of the Urinary Tract had been published in 2022. After the publication by the ENCR of the "Recommendations for coding bladder cancers" in 1995, knowledge about the biology and pathology of urinary tract tumors and their classification has varied and increased substantially. On the other hand, several studies have shown that cancer registries use different definitions, criteria for inclusion and coding of urothelial tumors. This great variability among registries affects not only the criteria for recording (registration, coding and classification) but also the criteria of reporting (counting in the statistics of incidence and survival) urinary tract tumors. This causes difficulties in the data comparability from different registries. Recording and reporting of urothelial tumors requires the application of standard criteria that must take into account the combination of the multiple aspects as the primary topography, the histological type, the grade, the extent of invasion, the multi-centricity, the progressions and the time interval between tumors. This led to the creation of a Working Group of the ENCR that developed these recommendations on the recording and reporting of urothelial tumors of the urinary tract. This article reports these recommendations and the rationale for each.
Language	English
Publishing date	2022-11-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2022.1046239
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