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REVIEW
Amirhossein Eslami Andargoli, Nalika Ulapane, Tuan Anh Nguyen, Nadeem Shuakat, John Zelcer, Nilmini Wickramasinghe
In the context of dementia care, Artificial Intelligence (AI) powered clinical decision support systems have the potential to enhance diagnosis and management. However, the scope and challenges of applying these technologies remain unclear. This scoping review aims to investigate the current state of AI applications in the development of intelligent decision support systems for dementia care. We conducted a comprehensive scoping review of empirical studies that utilised AI-powered clinical decision support systems in dementia care...
April 2024: Artificial Intelligence in Medicine
#2
Amber Shaheen, Glenn Bauman, Chantel Cacciotti, Shayna Zelcer, Sherif Ramadan
No abstract text is available yet for this article.
February 2024: Advances in Radiation Oncology
#3
JOURNAL ARTICLE
D Vacondio, H Nogueira Pinto, L Coenen, I A Mulder, R Fontijn, B van Het Hof, W K Fung, A Jongejan, G Kooij, N Zelcer, A J Rozemuller, H E de Vries, N M de Wit
In Alzheimer's disease (AD) more than 50% of the patients are affected by capillary cerebral amyloid-angiopathy (capCAA), which is characterized by localized hypoxia, neuro-inflammation and loss of blood-brain barrier (BBB) function. Moreover, AD patients with or without capCAA display increased vessel number, indicating a reactivation of the angiogenic program. The molecular mechanism(s) responsible for BBB dysfunction and angiogenesis in capCAA is still unclear, preventing a full understanding of disease pathophysiology...
November 28, 2023: Cell Death & Disease
#4
JOURNAL ARTICLE
M Florencia Tebele, Gastón Paris, Andrés Zelcer
Preventing bacterial development on surfaces is essential to avoid problems caused by biofouling. Surfaces decorated with gold nanoparticles have been shown to thermally kill bacteria under high-intensity NIR illumination. In this study, we evaluated the colonization by E. coli of nanostructured surfaces composed of mesoporous zirconia thin films, both with and without gold nanoparticles embedded into the pores. We studied the effect of the nanostructure and of low intensity visible light excitation of the gold nanoparticles on the colonization process...
October 2, 2023: Colloids and Surfaces. B, Biointerfaces
#5
JOURNAL ARTICLE
Anirban Das, Nicholas R Fernandez, Adrian Levine, Vanessa Bianchi, Lucie K Stengs, Jiil Chung, Logine Negm, Jose Rafael Dimayacyac, Yuan Chang, Liana Nobre, Ayse B Ercan, Santiago Sanchez-Ramirez, Sumedha Sudhaman, Melissa Edwards, Valerie Larouche, David Samuel, An Van Damme, David Gass, David S Ziegler, Stefan S Bielack, Carl Koschmann, Shayna Zelcer, Michal Yalon-Oren, Gadi Abede Campino, Tomasz Sarosiek, Kim E Nichols, Rebecca Loret De Mola, Kevin Bielamowicz, Magnus Sabel, Charlotta A Frojd, Matthew D Wood, Jason M Glover, Yi-Yen Lee, Magimairajan Vanan, Jenny K Adamski, Sebastien Perreault, Omar Chamdine, Magnus Aasved Hjort, Michal Zapotocky, Fernando Carceller, Erin Wright, Ivana Fedorakova, Alexander Lossos, Ryuma Tanaka, Michael Osborn, Deborah T Blumenthal, Melyssa Aronson, Ute Bartels, Annie Huang, Vijay Ramaswamy, David Malkin, Adam Shlien, Anita Villani, Peter B Dirks, Trevor J Pugh, Gad Getz, Yosef E Maruvka, Derek S Tsang, Birgit Ertl-Wagner, Cynthia Hawkins, Eric Bouffet, Daniel A Morgenstern, Uri Tabori
Immune-checkpoint inhibition (ICI) is effective for replication-repair deficient, high-grade gliomas (RRD-HGG). Clinical/biologic impact of immune-directed approaches after failing ICI-monotherapy are unknown. We performed an international study on 75 patients treated with anti-PD1; 20 are progression-free (median follow-up: 3.7-years). After 2nd-progression/recurrence (n=55), continuing ICI-based salvage prolonged survival to 11.6-months (n=38; p<0.001), particularly for those with extreme mutation burden (p=0...
October 12, 2023: Cancer Discovery
#6
REVIEW
Melanie Loix, Noam Zelcer, Jeroen F J Bogie, Jerome J A Hendriks
Lipids are essential molecules that play key roles in cell physiology by serving as structural components, for storage of energy, and in signal transduction. Hence, efficient regulation and maintenance of lipid homeostasis are crucial for normal cellular and tissue function. In the past decade, increasing research has shown the importance of ubiquitination in regulating the stability of key players in different aspects of lipid metabolism. This review describes recent insights into the regulation of lipid metabolism by ubiquitin signaling, discusses how ubiquitination can be targeted in diseases characterized by lipid dysregulation, and identifies areas that require further research...
September 26, 2023: Trends in Cell Biology
#7
JOURNAL ARTICLE
Sebastian Hendrix, Jenina Kingma, Roelof Ottenhoff, Masoud Valiloo, Monika Svecla, Lobke F Zijlstra, Vinay Sachdev, Kristina Kovac, Johannes H M Levels, Aldo Jongejan, Jan F de Boer, Folkert Kuipers, Antoine Rimbert, Giuseppe D Norata, Anke Loregger, Noam Zelcer
The sterol regulatory element binding proteins (SREBPs) are transcription factors that govern cholesterol and fatty acid metabolism. We recently identified SPRING as a post-transcriptional regulator of SREBP activation. Constitutive or inducible global ablation of Spring in mice is not tolerated, and we therefore develop liver-specific Spring knockout mice (LKO). Transcriptomics and proteomics analysis reveal attenuated SREBP signaling in livers and hepatocytes of LKO mice. Total plasma cholesterol is reduced in male and female LKO mice in both the low-density lipoprotein and high-density lipoprotein fractions, while triglycerides are unaffected...
August 25, 2023: Nature Communications
#8
JOURNAL ARTICLE
Sebastian Hendrix, Noam Zelcer
PURPOSE OF REVIEW: The SREBP transcription factors are master regulators of lipid homeostasis owing to their role in controlling cholesterol and fatty acid metabolism. The core machinery required to promote their trafficking and proteolytic activation has been established close to 20 years ago. In this review, we summarize the current understanding of a newly identified regulator of SREBP signaling, SPRING (formerly C12ORF49), its proposed mechanism of action, and its role in lipid metabolism...
August 4, 2023: Current Opinion in Lipidology
#9
REVIEW
Leona Kosowicz, Kham Tran, Toan Tran Khanh, Thu Ha Dang, Van An Pham, Hue Ta Thi Kim, Hoang Thi Bach Duong, Tran Dong Nguyen, Anh Tuyet Phuong, Trong Hieu Le, Van Anh Ta, Nilmini Wickramasinghe, Penelope Schofield, John Zelcer, Tuan Pham Le, Tuan Anh Nguyen
BACKGROUND: A rapidly aging population, a shifting disease burden and the ongoing threat of infectious disease outbreaks pose major concerns for Vietnam's health care system. Health disparities are evident in many parts of the country, especially in rural areas, and the population faces inequitable access to patient-centered health care. Vietnam must therefore explore and implement advanced solutions to the provision of patient-centered care, with a view to reducing pressures on the health care system simultaneously...
April 5, 2023: Journal of Medical Internet Research
#10
JOURNAL ARTICLE
Bram W van Os, Winnie G Vos, Laura A Bosmans, Claudia M van Tiel, Sanne C Lith, Myrthe S den Toom, Linda Beckers, Johannes H M Levels, Suzanne A E van Wouw, Noam Zelcer, Esther A Zaal, Celia R Berkers, Chris H A van der Lest, J Bernd Helms, Christian Weber, Dorothee Atzler, Menno P J de Winther, Jeroen Baardman, Esther Lutgens
AIMS: Hyperlipidemia and T cell driven inflammation are important drivers of atherosclerosis, the main underlying cause of cardiovascular disease. Here, we detailed the effects of hyperlipidemia on T cells. METHODS AND RESULTS: In vitro, exposure of human and murine CD4+ T cells to very low-density lipoprotein (VLDL), but not to low-density lipoprotein (LDL) resulted in upregulation of Th1 associated pathways. VLDL was taken up via a CD36-dependent pathway and resulted in membrane stiffening and a reduction in lipid rafts...
March 2023: Eur Heart J Open
#11
JOURNAL ARTICLE
Robert D Friedberg, Jasmine Thomas, Joshua Tiller-Ormord, Ciera Korte, Kimberly Brown, Eunice Mendez, Yasaman Mohavedi, Hannah Zelcer
The COVID-19 viral outbreak is a one in 100 year public health crisis. In addition to the stunning morbidity and mortality rates related to infection, multiple psychiatric sequelae erupted. Unfortunately, children and adolescents are neither immune to infection nor to the emotional consequences associated with the pandemic. Not surprisingly, the field's understanding of the psychological consequences of the viral outbreak are nascent. Consequently, this study examines the relationship between parents' and children's intolerance of uncertainty (IU) and their reactions to COVID-19...
February 8, 2023: Clinical Child Psychology and Psychiatry
#12
JOURNAL ARTICLE
Suzanne A E van Wouw, Marlene van den Berg, Maroua El Ouraoui, Amber Meurs, Jenina Kingma, Roelof Ottenhoff, Melanie Loix, Marten A Hoeksema, Koen Prange, Gerard Pasterkamp, Jerome J A Hendriks, Jeroen F J Bogie, Jan B van Klinken, Frederic M Vaz, Aldo Jongejan, Menno P J de Winther, Noam Zelcer
Lysoplasmalogens are a class of vinyl ether bioactive lipids that have a central role in plasmalogen metabolism and membrane fluidity. The liver X receptor transcription factors (LXR) are important determinants of cellular lipid homeostasis owing to their ability to regulate cholesterol and fatty acid metabolism. However, their role in governing the composition of lipid species such as lysoplasmalogens in cellular membranes is less well studied. Here, we mapped the lipidome of bone marrow-derived macrophages (BMDM) following LXR activation...
December 30, 2022: Journal of Lipid Research
#13
JOURNAL ARTICLE
Nilmini Wickramasinghe, Nalika Ulapane, Tuan Anh Nguyen, Amir Andargoli, Chinedu Ossai, Nadeem Shuakat, John Zelcer
BACKGROUND: Digital twins in healthcare is an emerging area. Twins are created from data of past patients. The objective is to facilitate data-driven decision support for clinicians for more precise and personalized dementia care. The project has three phases: (1) Twin discovering algorithm development from synthetic data; (2) Algorithm validation with real patient data; (3) Clinical implementation. The current work is related to Phase 1. METHOD: Past subjects (n=30) showing cognitive decline (based on MMSE scores) mimicking a sample monitored over three years (i...
December 2022: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
#14
JOURNAL ARTICLE
Lisa Willemsen, Koen H M Prange, Annette E Neele, Cindy P A A van Roomen, Marion Gijbels, Guillermo R Griffith, Myrthe den Toom, Linda Beckers, Ricky Siebeler, Nathanael J Spann, Hung-Jen Chen, Laura A Bosmans, Andrej Gorbatenko, Suzanne van Wouw, Noam Zelcer, Heinz Jacobs, Fred van Leeuwen, Menno P J de Winther
Macrophages are critical immune cells in inflammatory diseases, and their differentiation and function are tightly regulated by histone modifications. H3K79 methylation is a histone modification associated with active gene expression, and DOT1L is the only histone methyltransferase for H3K79. Here we determine the role of DOT1L in macrophages by applying a selective DOT1L inhibitor in mouse and human macrophages and using myeloid-specific Dot1l-deficient mice. We found that DOT1L directly regulates macrophage function by controlling lipid biosynthesis gene programs including central lipid regulators like sterol regulatory element-binding proteins SREBP1 and SREBP2...
November 22, 2022: Cell Reports
#15
REVIEW
Camilla Ruffilli, Sascha Roth, Monica Rodrigo, Helen Boyd, Noam Zelcer, Kevin Moreau
Targeted protein degradation (TPD) is a promising therapeutic modality to modulate protein levels and its application promises to reduce the "undruggable" proteome. Among TPD strategies, Proteolysis TArgeting Chimera (PROTAC) technology has shown a tremendous potential with attractive advantages when compared to the inhibition of the same target. While PROTAC technology has had a significant impact in scientific research, its application to degrade integral membrane proteins (IMPs) is still in its beginnings...
October 14, 2022: ACS Pharmacology & Translational Science
#16
JOURNAL ARTICLE
Jiil Chung, Logine Negm, Vanessa Bianchi, Lucie Stengs, Anirban Das, Zhihui Amy Liu, Sumedha Sudhaman, Melyssa Aronson, Ledia Brunga, Melissa Edwards, Victoria Forster, Martin Komosa, Scott Davidson, Jodi Lees, Patrick Tomboc, David Samuel, Roula Farah, Anne Bendel, Jeffrey Knipstein, Kami Wolfe Schneider, Agnes Reschke, Shayna Zelcer, Alexandra Zorzi, Robert McWilliams, William D Foulkes, Raymond Bedgood, Lindsay Peterson, Sara Rhode, An Van Damme, Isabelle Scheers, Sharon Gardner, Gabriel Robbins, Magimairajan Issai Vanan, M Stephen Meyn, Rebecca Auer, Brandie Leach, Carol Burke, Anita Villani, David Malkin, Eric Bouffet, Annie Huang, Michael D Taylor, Carol Durno, Adam Shlien, Cynthia Hawkins, Gad Getz, Yosef E Maruvka, Uri Tabori
PURPOSE: Diagnosis of Mismatch Repair Deficiency (MMRD) is crucial for tumor management and early detection in patients with the cancer predisposition syndrome constitutional mismatch repair deficiency (CMMRD). Current diagnostic tools are cumbersome and inconsistent both in childhood cancers and in determining germline MMRD. PATIENTS AND METHODS: We developed and analyzed a functional Low-pass Genomic Instability Characterization (LOGIC) assay to detect MMRD. The diagnostic performance of LOGIC was compared with that of current established assays including tumor mutational burden, immunohistochemistry, and the microsatellite instability panel...
February 1, 2023: Journal of Clinical Oncology
#17
REVIEW
Nilmini Wickramasinghe, Nalika Ulapane, Amir Andargoli, Chinedu Ossai, Nadeem Shuakat, Tuan Nguyen, John Zelcer
In this perspective paper, we want to highlight the potential benefits of incorporating digital twins to support better dementia care. In particular, we assert that, by doing so, it is possible to ensure greater precision regarding dementia care while simultaneously enhancing personalization. Digital twins have been used successfully in manufacturing to enable better prediction and tailoring of solutions to meet required needs, and thereby have enabled more effective and efficient deployment of resources. We develop a model for digital twin in the healthcare domain as a clinical decision support tool by extrapolating its current uses from the manufacturing domain...
October 2022: JAMIA Open
#18
JOURNAL ARTICLE
Paula Y Steinberg, Nicolás I Krimer, Gabriela P Sarmiento, Darío Rodrigues, Cristián Huck-Iriart, Daniel Clemens, Andrés Zelcer, Martín Mirenda
Direct back-face transmission steady-state fluorescence was successfully applied to the study of aggregation of ibuprofen and ibuprofenate anion in solution taking advantage of its own fluorescence. The analysis of the experimental data involves the use of the differential reabsorption model to account for re-absorption phenomenon and the closed association model to describe aggregation. The fluorescence quantum yield of ibuprofenate increases when it aggregates in the presence of sodium, but it markedly decreases when 1-butyl-3-methylimidazolium is used as counterion...
September 2022: Photochemical & Photobiological Sciences
#19
JOURNAL ARTICLE
Jamie Kane, Matthijs Jansen, Sebastian Hendrix, Laura A Bosmans, Linda Beckers, Claudia van Tiel, Marion Gijbels, Noam Zelcer, Carlie J de Vries, Philipp von Hundelshausen, Marc Vervloet, Ed Eringa, Anton J Horrevoets, Niels van Royen, Esther Lutgens
BACKGROUND: Galectins have numerous cellular functions in immunity and inflammation. Short-term galectin-2 (Gal-2) blockade in ischemia-induced arteriogenesis shifts macrophages to an anti-inflammatory phenotype and improves perfusion. Gal-2 may also affect other macrophage-related cardiovascular diseases. OBJECTIVES: This study aims to elucidate the effects of Gal-2 inhibition in atherosclerosis. METHODS: ApoE -/- mice were given a high-cholesterol diet (HCD) for 12 weeks...
June 2022: Thrombosis and Haemostasis
#20
JOURNAL ARTICLE
L E Larsen, M A W van den Boogert, W A Rios-Ocampo, J C Jansen, D Conlon, P L E Chong, J H M Levels, R E Eilers, V V Sachdev, N Zelcer, T Raabe, M He, N J Hand, J P H Drenth, D J Rader, E S G Stroes, D J Lefeber, J W Jonker, A G Holleboom
BACKGROUND: Recently, novel inborn errors of metabolism were identified due to mutations in V-ATPase assembly factors TMEM199 and CCDC115. Patients are characterized by generalized protein glycosylation defects, hypercholesterolemia and fatty liver disease. Here, we set out to characterize the lipid and fatty liver phenotype in human plasma, cell models and a mouse model. METHODS AND RESULTS: Patients with TMEM199 and CCDC115 mutations displayed hyperlipidemia, characterized by increased levels of lipoproteins in the very-low density lipoprotein (VLDL) range...
October 6, 2021: Cellular and Molecular Gastroenterology and Hepatology
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