Multi-feature computational framework for combined signatures of dementia in underrepresented settings

PUBLISHED 25 August 2022Objective. The differential diagnosis of behavioral variant frontotemporal dementia (bvFTD) and Alzheimer’s disease (AD) remains challenging in underrepresented, underdiagnosed groups, including Latinos, as advanced biomarkers are rarely available. Recent guidelines for the study of dementia highlight the critical role of biomarkers. Thus, novel cost-effective complementary approaches are required in clinical settings. Approach. We developed a novel framework based on a gradient boosting machine learning classifier, tuned by Bayesian optimization, on a multi-feature multimodal approach (combining demographic, neuropsychological, magnetic resonance imaging (MRI), and electroencephalography/functional MRI connectivity data) to characterize neurodegeneration using site harmonization and sequential feature selection. We assessed 54 bvFTD and 76 AD patients and 152 healthy controls (HCs) from a Latin American consortium (ReDLat). Main results. The multimodal model yielded high area under the curve classification values (bvFTD patients vs HCs: 0.93 (±0.01); AD patients vs HCs: 0.95 (±0.01); bvFTD vs AD patients: 0.92 (±0.01)). The feature selection approach successfully filtered non-informative multimodal markers (from thousands to dozens). Results. Proved robust against multimodal heterogeneity, sociodemographic variability, and missing data. Significance. The model accurately identified dementia subtypes using measures readily available in underrepresented settings, with a similar performance than advanced biomarkers. This approach, if confirmed and replicated, may potentially complement clinical assessments in developing countries.Sebastian Moguilner, Agustina Birba, Sol Fittipaldi, Cecilia Gonzalez-Campo, Enzo Tagliazucchi, Pablo Reyes, Diana Matallana, Mario A Parra, Andrea Slachevsky, Gonzalo Farías, Josefina Cruzat, Adolfo García, Harris A Eyre, Renaud La Joie, Gil Rabinovici, Robert Whelan and Agustín Ibáñe

Teaching the Process of Molecular Phylogeny and Systematics: A Multi-Part Inquiry-Based Exercise

Three approaches to molecular phylogenetics are demonstrated to biology students as they explore molecular data from Homo sapiens and four related primates. By analyzing DNA sequences, protein sequences, and chromosomal maps, students are repeatedly challenged to develop hypotheses regarding the ancestry of the five species. Although these exercises were designed to supplement and enhance classroom instruction on phylogeny, cladistics, and systematics in the context of a postsecondary majors-level introductory biology course, the activities themselves require very little prior student exposure to these topics. Thus, they are well suited for students in a wide range of educational levels, including a biology class at the secondary level. In implementing this exercise, we have observed measurable gains, both in student comprehension of molecular phylogeny and in their acceptance of modern evolutionary theory. By engaging students in modern phylogenetic activities, these students better understood how biologists are currently using molecular data to develop a more complete picture of the shared ancestry of all living things

A phase-specific neuroimmune model of clinical depression

Immune dysfunction and pro-inflammatory states in particular have been implicated in the aetiology and pathogenesis of depression. Whilst the onset of an episode and certain symptoms of depression appear well explained by this inflammatory model, the underpinnings of the episodic and progressive nature, as well as relapse and remission status in depression require attention. In this review it is suggested that additional immune factors beyond pro- and anti-inflammatory cytokines may effectively contribute to the understanding of the neurobiology of clinical depression. Considering neurobiological effects of immunomodulatory factors such as T cells, macrophages, microglia and astrocytes relevant to depression, we suggest a neuroimmune model of depression underpinned by dynamic immunomodulatory processes. This perspective paper then outlines a neuroimmune model of clinical phases of depression in an attempt to more adequately explain depression-like behaviours in pre-clinical models and the dynamic nature of depression in clinical populations. Finally, the implications for immunomodulatory treatments of depression are considered

Growing the clinical academic workforce: the case for structured academic training programs for junior doctors

Harris A Eyre, Rob D Mitchell, William J Milfor

Listening to the silent struggles of bipolar disorder through sonification of iMoodJournal data

First published: 07 May 2022This paper reports a preliminary case study for demonstrating the potential of data sonification for telling a real-life narrative of experienced mood swings through music. We obtained iMoodJournal data (2017–2020) from a voluntarily participating male who was diagnosed with type 2 bipolar disorder in 2015. The monitored period covers prolonged stretches of severe depression, particularly during fall, winter, and spring months. These “winter depressions” were usually superseded by remission during summer. These seasonal patterns were similar and recurring in the period between 2017 and 2019. In 2020, the depressions were relatively mild due to the patient spending winter in southern latitudes. However, another severe depression episode occurred during summer 2020 instead, which likely emanated from a period of medication discontinuation. The symptomatology was overall complex and highly dynamic, manifested in the combination of mood specifying tags that the user associated with determined mood scores in the iMoodJournal. This complexity was difficult to capture in the form of the numerical scores visualized in Figures S1 and S2.David G. Angeler, Harris A. Eyre, Michael Ber

Intervertebral disc regeneration: Influence of growth factors on differentiation of human mesenchymal stem cells (hMSC)

Introduction: One common cause of disability in modern society is low back pain. The main reason for this pain is the degeneration of the intervertebral disc (IVD), particular of the nucleus pulposus (NP). For an early degeneration stage cell-based therapy would be a minimal invasive method of treatment. Therefore, adequate cells are needed. As the usage of NP cells is limited because of their insufficient amount or vitality, a promising alternative is the application of human mesenchymal stem cells (hMSCs). Objective: To investigate the potential of various growth factors to induce the differentiation of hMSCs into NP cells and thereby to obtain an alternative cell source for the treatment of IVD degeneration. Methods: hMSC-TERT were cultivated three-dimensionally in a hydrogel for 21 days to form NP cells. Cell survival and proliferation were determined using SybrGreen/propidium iodide double staining and the WST-test. To investigate the ability of several growth factors to differentiate hMSCs into NP cells, fluorescence immunostaining of NP-specific marker proteins (e.g. chondroadherin (CHAD) and the recently discovered cytokeratin 19 [1]) was performed. Results: Following the procedure described above, cells are able to maintain their viability and proliferation capacity throughout the cultivation time. By using a previously established immunofluorescence protocol, we could indicate the ability of three different growth factors to differentiate hMSCs into NP-like cells. Conclusion: The expression of several marker proteins in all differentiation experiments indicates the ability of IGF-1, FGF-2 and PDGF-BB to differentiate hMSCs into NP-like cells apart from the usually applied TGF-β3. Furthermore, our findings preclude the application of Cytokeratin 19 as a specific marker protein for NP cells [1]. Further experiments have to be done to find real specific NP marker proteins to indisputable verify the differentiation of hMSCs into NP cells. If so, application of the mentioned three growth factors would possibly be an option to obtain sufficient NP cells for minimal invasive IVD regeneration

Promoting tech transfer between space and global mental health

INTRODUCTION: Numerous issues in mental health benefit from technological innovation. An example involves the mental health challenges of long-duration spaceflight (such as a Mars mission), including prolonged confinement, microgravity, and different sunlight exposure lengths. Persisting on Earth are global mental health challenges stemming from disease burdens, limited interview-based diagnostic systems, trial-and-error treatment approaches, and suboptimal access. There is potential for cross-pollinating solutions between these seemingly disparate challenges using a range of emerging technologies such as sensors, omics, and big data. In this review, we highlight the bidirectional value of mental health technology transfer aimed to address issues both on Earth and in space. METHODS: We prepared a systematic review of studies pertaining to mental health technological innovation and space medicine. RESULTS: For Earth mental health technologies translatable to long-duration space missions, we cite several example technologies, including device-based psychotherapy and social support, conversational agents aka chatbots, and nutritional and physical activity focused mental health. Space technologies translatable to Earth mental health include remote sensing devices, global navigation satellite systems, satellite communications, chronotherapies, and nutritional advances. DISCUSSION: There is a rich history of space technologies informing Earth technological trends, including general health care on Earth, and vice versa. To avoid the traditional happenstance approach that results in delays, missed opportunities, and increased cost, and to improve outcomes for both Earth and space utilization of these technologies, we propose increased dialogue and training opportunities to enhance innovation and outcomes.Donald D. Chang, Eric A. Storch, Lance Black, Michael Berk, Neal Pellis ... Harris A. Eyre ... et al