Automatic wheeze detection based on auditory modelling

Automatic wheeze detection has several potential benefits compared with reliance on human auscultation: it is experience independent, an automated historical record can easily be kept, and it allows quantification of wheeze severity. Previous attempts to detect wheezes automatically have had partial success but have not been reliable enough to become widely accepted as a useful tool. In this paper an improved algorithm for automatic wheeze detection based on auditory modelling is developed, called the frequency- and duration-dependent threshold algorithm. The mean frequency and duration of each wheeze component are obtained automatically. The detected wheezes are marked on a spectrogram. In the new algorithm, the concept of a frequency- and duration-dependent threshold for wheeze detection is introduced. Another departure from previous work is that the threshold is based not on global power but on power corresponding to a particular frequency range. The algorithm has been tested on 36 subjects, 11 of whom exhibited characteristics of wheeze. The results show a marked improvement in the accuracy of wheeze detection when compared with previous algorithms

Comparative interactomics analysis of different ALS-associated proteins identifies converging molecular pathways

Amyotrophic lateral sclerosis (ALS) is a devastating neurological disease with no effective treatment available. An increasing number of genetic causes of ALS are being identified, but how these genetic defects lead to motor neuron degeneration and to which extent they affect common cellular pathways remains incompletely understood. To address these questions, we performed an interactomic analysis to identify binding partners of wild-type (WT) and ALS-associated mutant versions of ATXN2, C9orf72, FUS, OPTN, TDP-43 and UBQLN2 in neuronal cells. This analysis identified several known but also many novel binding partners of these proteins

Dorsal Root Ganglia Macrophages Maintain Osteoarthritis Pain

Pain is the major debilitating symptom of osteoarthritis (OA), which is difficult to treat. In OA patients joint tissue damage only poorly associates with pain, indicating other mechanisms contribute to OA pain. Immune cells regulate the sensory system, but little is known about the involvement of immune cells in OA pain. Here, we report that macrophages accumulate in the dorsal root ganglia (DRG) distant from the site of injury in two rodent models of OA. DRG macrophages acquired an M1-like phenotype, and depletion of DRG macrophages resolved OA pain in male and female mice. Sensory neurons innervating the damaged knee joint shape DRG macrophages into an M1-like phenotype. Persisting OA pain, accumulation of DRG macrophages, and programming of DRG macrophages into an M1-like phenotype were independent of Nav1.8 nociceptors. Inhibition of M1-like macrophages in the DRG by intrathecal injection of an IL4-IL10 fusion protein or M2-like macrophages resolved persistent OA pain. In conclusion, these findings reveal a crucial role for macrophages in maintaining OA pain independent of the joint damage and suggest a new direction to treat OA pain. SIGNIFICANCE STATEMENT: In OA patients pain poorly correlates with joint tissue changes indicating mechanisms other than only tissue damage that cause pain in OA. We identified that DRG containing the somata of sensory neurons innervating the damaged knee are infiltrated with macrophages that are shaped into an M1-like phenotype by sensory neurons. We show that these DRG macrophages actively maintain OA pain remotely and independent of joint damage. The phenotype of these macrophages is crucial for a pain-promoting role. Targeting the phenotype of DRG macrophages with either M2-like macrophages or a cytokine fusion protein that skews macrophages into an M2-like phenotype resolves OA pain. Our work reveals a mechanism that contributes to the maintenance of OA pain distant from the affected knee joint and suggests that dorsal root ganglia macrophages are a target to treat osteoarthritis chronic pain

Stage-specific functions of Semaphorin7A during adult hippocampal neurogenesis rely on distinct receptors

The guidance protein Semaphorin7A (Sema7A) is required for the proper development of the immune and nervous systems. Despite strong expression in the mature brain, the role of Sema7A in the adult remains poorly defined. Here we show that Sema7A utilizes different cell surface receptors to control the proliferation and differentiation of neural progenitors in the adult hippocampal dentate gyrus (DG), one of the select regions of the mature brain where neurogenesis occurs. PlexinC1 is selectively expressed in early neural progenitors in the adult mouse DG and mediates the inhibitory effects of Sema7A on progenitor proliferation. Subsequently, during differentiation of adult-born DG granule cells, Sema7A promotes dendrite growth, complexity and spine development through β1-subunit-containing integrin receptors. Our data identify Sema7A as a key regulator of adult hippocampal neurogenesis, providing an example of how differential receptor usage spatiotemporally controls and diversifies the effects of guidance cues in the adult brain

Glycan-dependent binding of galectin-1 to neuropilin-1 promotes axonal regeneration after spinal cord injury

Following spinal cord injury (SCI), semaphorin 3A (Sema3A) prevents axonal regeneration through binding to the neuropilin-1 (NRP-1)/PlexinA4 receptor complex. Here, we show that galectin-1 (Gal-1), an endogenous glycan-binding protein, selectively bound to the NRP-1/PlexinA4 receptor complex in injured neurons through a glycan-dependent mechanism, interrupts the Sema3A pathway and contributes to axonal regeneration and locomotor recovery after SCI. Although both Gal-1 and its monomeric variant contribute to de-activation of microglia, only high concentrations of wild-type Gal-1 (which co-exists in a monomer-dimer equilibrium) bind to the NRP-1/PlexinA4 receptor complex and promote axonal regeneration. Our results show that Gal-1, mainly in its dimeric form, promotes functional recovery of spinal lesions by interfering with inhibitory signals triggered by Sema3A binding to NRP-1/PlexinA4 complex, supporting the use of this lectin for the treatment of SCI patients.Fil: Quintá, Héctor Ramiro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; ArgentinaFil: Pasquini, Juana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; ArgentinaFil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Pasquini, Laura Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentin

Shear-stress and wall-stress regulation of vascular remodeling after balloon angioplasty: effect of matrix metalloproteinase inhibition

BACKGROUND: Constrictive vascular remodeling (VR) is the most significant component of restenosis after balloon angioplasty (PTA). Whereas in physiologi

Принципы организации объектно-ориентированных систем обработки неформализованной информации

Рассматривается класс логико-аналитических систем, использующих специальные лингвистические процессоры и базы знаний (БЗ) для обработки потоков неформализованных документов с целью решения пользовательских задач. На первом этапе формализации текста документа извлекаются информационные объекты и связи, которые образуют структуры знаний и запоминаются в БЗ. На уровне БЗ организуются различные виды анализа и объектных поисков: поиск похожих объектов и ситуаций, поиск по связям и другие. Рассматриваются основные компоненты подобных систем, называемых объектно-ориентированными, их особенности при использовании в различных приложениях: при обработке криминальной информации, при автоматической формализации резюме (заявок на работу), в системах обработки СМИ с выделением террористических групп и их деяний.A class of the logical-analytical systems using special linguistic processors and knowledge bases is considered. Such systems are called object-oriented. These systems are employed for processing of the unstructured documents flow for the user problems decision. At the first stage the document text is formalized: information objects and links are extracted and transferred into the knowledge structures which are stored in the knowledge base (KB). At the level of KB various kinds of analysis and object search are organized: the search for similar objects and situations, the search on the basis of links and other types of search. The basic components of these systems, their main features and the particular use in different applications are considered.The system operation in the subject areas of criminal information processing, automatic formalization of summary texts (applications for work), mass media analysis for extracting information about terrorist formations and their activities are presented

An agenda-setting paper on data sharing platforms: euCanSHare workshop [version 1; peer review: awaiting peer review]

Various data sharing platforms are being developed to enhance the sharing of cohort data by addressing the fragmented state of data storage and access systems. However, policy challenges in several domains remain unresolved. The euCanSHare workshop was organized to identify and discuss these challenges and to set the future research agenda. Concerns over the multiplicity and long-term sustainability of platforms, lack of resources, access of commercial parties to medical data, credit and recognition mechanisms in academia and the organization of data access committees are outlined. Within these areas, solutions need to be devised to ensure an optimal functioning of platforms