scholarly journals Multiregional Sequencing of IDH-WT Glioblastoma Reveals High Genetic Heterogeneity and a Dynamic Evolutionary History

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2044
Author(s):  
Sara Franceschi ◽  
Prospero Civita ◽  
Francesco Pasqualetti ◽  
Francesca Lessi ◽  
Martina Modena ◽  
...  
Keyword(s):  
Tumor Heterogeneity ◽  
Evolutionary Dynamics ◽  
Poor Overall Survival ◽  
The Past ◽  
Whole Exome ◽  
Spatially Distributed ◽  
Number Variation ◽  
Primary Neoplasms ◽  
One Year ◽  
The Brain

Glioblastoma is one of the most common and lethal primary neoplasms of the brain. Patient survival has not improved significantly over the past three decades and the patient median survival is just over one year. Tumor heterogeneity is thought to be a major determinant of therapeutic failure and a major reason for poor overall survival. This work aims to comprehensively define intra- and inter-tumor heterogeneity by mapping the genomic and mutational landscape of multiple areas of three primary IDH wild-type (IDH-WT) glioblastomas. Using whole exome sequencing, we explored how copy number variation, chromosomal and single loci amplifications/deletions, and mutational burden are spatially distributed across nine different tumor regions. The results show that all tumors exhibit a different signature despite the same diagnosis. Above all, a high inter-tumor heterogeneity emerges. The evolutionary dynamics of all identified mutations within each region underline the questionable value of a single biopsy and thus the therapeutic approach for the patient. Multiregional collection and subsequent sequencing are essential to try to address the clinical challenge of precision medicine. Especially in glioblastoma, this approach could provide powerful support to pathologists and oncologists in evaluating the diagnosis and defining the best treatment option.

Osseointegration interface of calcified bone and endosseous implants

1992 ◽  
Vol 50 (2) ◽  
pp. 1096-1097
Author(s):  
K.E. Krizan ◽  
J.E. Laffoon ◽  
M.J. Buckley
Keyword(s):  
Structure And Function ◽  
Titanium Implants ◽  
En Bloc ◽  
Endosseous Implants ◽  
Ultrastructural Studies ◽  
The Past ◽  
Cacodylate Buffer ◽  
One Year ◽  
And Function

With increase use of tissue-integrated prostheses in recent years it is a goal to understand what is happening at the interface between haversion bone and bulk metal. This study uses electron microscopy (EM) techniques to establish parameters for osseointegration (structure and function between bone and nonload-carrying implants) in an animal model. In the past the interface has been evaluated extensively with light microscopy methods. Today researchers are using the EM for ultrastructural studies of the bone tissue and implant responses to an in vivo environment. Under general anesthesia nine adult mongrel dogs received three Brånemark (Nobelpharma) 3.75 × 7 mm titanium implants surgical placed in their left zygomatic arch. After a one year healing period the animals were injected with a routine bone marker (oxytetracycline), euthanized and perfused via aortic cannulation with 3% glutaraldehyde in 0.1M cacodylate buffer pH 7.2. Implants were retrieved en bloc, harvest radiographs made (Fig. 1), and routinely embedded in plastic. Tissue and implants were cut into 300 micron thick wafers, longitudinally to the implant with an Isomet saw and diamond wafering blade [Beuhler] until the center of the implant was reached.

Neuro-Clinical Signatures of Language Impairments: A Theoretical Framework for Function-to-structure Mapping in Clinics

2020 ◽  
Vol 20 (9) ◽  
pp. 800-811 ◽  
Author(s):  
Ferath Kherif ◽  
Sandrine Muller
Keyword(s):  
Brain Mapping ◽  
Theoretical Framework ◽  
Brain Regions ◽  
Language Impairments ◽  
Structure Mapping ◽  
Language Functions ◽  
The Past ◽  
Language Recovery ◽  
The Brain ◽  
Bow Tie

In the past decades, neuroscientists and clinicians have collected a considerable amount of data and drastically increased our knowledge about the mapping of language in the brain. The emerging picture from the accumulated knowledge is that there are complex and combinatorial relationships between language functions and anatomical brain regions. Understanding the underlying principles of this complex mapping is of paramount importance for the identification of the brain signature of language and Neuro-Clinical signatures that explain language impairments and predict language recovery after stroke. We review recent attempts to addresses this question of language-brain mapping. We introduce the different concepts of mapping (from diffeomorphic one-to-one mapping to many-to-many mapping). We build those different forms of mapping to derive a theoretical framework where the current principles of brain architectures including redundancy, degeneracy, pluri-potentiality and bow-tie network are described.

Chemo- and Optogenetic Strategies for the Elucidation of Pain Pathways

2019 ◽  
pp. 816-832 ◽  
Author(s):  
Sascha R. A. Alles ◽  
Anne-Marie Malfait ◽  
Richard J. Miller
Keyword(s):  
Chronic Pain ◽  
Pain Response ◽  
Conscious Perception ◽  
Novel Therapies ◽  
The Past ◽  
Nociceptive Pathways ◽  
Pain Pathways ◽  
Technical Advances ◽  
The Brain

Pain is not a simple phenomenon and, beyond its conscious perception, involves circuitry that allows the brain to provide an affective context for nociception, which can influence mood and memory. In the past decade, neurobiological techniques have been developed that allow investigators to elucidate the importance of particular groups of neurons in different aspects of the pain response, something that may have important translational implications for the development of novel therapies. Chemo- and optogenetics represent two of the most important technical advances of recent times for gaining understanding of physiological circuitry underlying complex behaviors. The use of these techniques for teasing out the role of neurons and glia in nociceptive pathways is a rapidly growing area of research. The major findings of studies focused on understanding circuitry involved in different aspects of nociception and pain are highlighted in this article. In addition, attention is drawn to the possibility of modification of chemo- and optogenetic techniques for use as potential therapies for treatment of chronic pain disorders in human patients.

scholarly journals Hepatitis and tuberculosis testing are much less common than HIV testing among adults in Kisumu, Kenya: results from a cross-sectional assessment

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Joshua Tunnage ◽  
Adam Yates ◽  
Chiaka Nwoga ◽  
Valentine Sing’oei ◽  
John Owuoth ◽  
...  
Keyword(s):  
Secondary Education ◽  
Viral Hepatitis ◽  
Hiv Testing ◽  
Spatial Location ◽  
Tuberculosis Screening ◽  
Cross Sectional ◽  
The Past ◽  
Prior Testing ◽  
Testing Uptake ◽  
One Year

Abstract Background Kenya has a high burden of HIV, viral hepatitis, and tuberculosis. Screening is necessary for early diagnosis and treatment, which reduces morbidity and mortality across all three illnesses. We evaluated testing uptake for HIV, viral hepatitis, and tuberculosis in Kisumu, Kenya. Methods Cross-sectional data from adults aged 18–35 years who enrolled in a prospective HIV incidence cohort study from February 2017 to May 2018 were analyzed. A questionnaire was administered to each participant at screening for study eligibility to collect behavioral characteristics and to assess prior testing practices. Among participants without a history of previously-diagnosed HIV, multivariable robust Poisson regression was used to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) for factors potentially associated with HIV testing in the 12 months prior to enrollment. A hierarchical model was used to test for differential access to testing due to spatial location. Results Of 671 participants, 52 (7.7%) were living with HIV, 308 (45.9%) were female, and the median age was 24 (interquartile range 21–28) years. Among 651 (97.0%) who had ever been tested for HIV, 400 (61.2%) reported HIV testing in the past 6 months, 129 (19.7%) in the past 6–12 months, and 125 (19.1%) more than one year prior to enrollment. Any prior testing for viral hepatitis was reported by 8 (1.2%) participants and for tuberculosis by 51 (7.6%). In unadjusted models, HIV testing in the past year was more common among females (PR 1.08 [95% CI 1.01, 1.17]) and participants with secondary education or higher (PR 1.10 [95% CI 1.02, 1.19]). In the multivariable model, only secondary education or higher was associated with recent HIV testing (adjusted PR 1.10 [95% CI 1.02, 1.20]). Hierarchical models showed no geographic differences in HIV testing across Kisumu subcounties. Conclusions Prior HIV testing was common among study participants and most had been tested within the past year but testing for tuberculosis and viral hepatitis was far less common. HIV testing gaps exist for males and those with lower levels of education. HIV testing infrastructure could be leveraged to increase access to testing for other endemic infectious diseases.

scholarly journals Impact of Coronavirus Outbreaks on Science and Society: Insights from Temporal Bibliometry of SARS and COVID-19

Entropy ◽  
2021 ◽  
Vol 23 (5) ◽  
pp. 626
Author(s):  
Ramya Gupta ◽  
Abhishek Prasad ◽  
Suresh Babu ◽  
Gitanjali Yadav
Keyword(s):  
Published Data ◽  
Science And Society ◽  
Time Dimension ◽  
Scientific Publications ◽  
The Past ◽  
Economic Trends ◽  
Global Events ◽  
One Year ◽  
Personal Devices ◽  
Share Information

A global event such as the COVID-19 crisis presents new, often unexpected responses that are fascinating to investigate from both scientific and social standpoints. Despite several documented similarities, the coronavirus pandemic is clearly distinct from the 1918 flu pandemic in terms of our exponentially increased, almost instantaneous ability to access/share information, offering an unprecedented opportunity to visualise rippling effects of global events across space and time. Personal devices provide “big data” on people’s movement, the environment and economic trends, while access to the unprecedented flurry in scientific publications and media posts provides a measure of the response of the educated world to the crisis. Most bibliometric (co-authorship, co-citation, or bibliographic coupling) analyses ignore the time dimension, but COVID-19 has made it possible to perform a detailed temporal investigation into the pandemic. Here, we report a comprehensive network analysis based on more than 20,000 published documents on viral epidemics, authored by over 75,000 individuals from 140 nations in the past one year of the crisis. Unlike the 1918 flu pandemic, access to published data over the past two decades enabled a comparison of publishing trends between the ongoing COVID-19 pandemic and those of the 2003 SARS epidemic to study changes in thematic foci and societal pressures dictating research over the course of a crisis.

scholarly journals DNA Methylation Profiles of Tph1A and BDNF in Gut and Brain of L. Rhamnosus-Treated Zebrafish

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 142
Author(s):  
Mariella Cuomo ◽  
Luca Borrelli ◽  
Rosa Della Monica ◽  
Lorena Coretti ◽  
Giulia De Riso ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Molecular Mechanisms ◽  
The Past ◽  
Targeted Analysis ◽  
Lack Of Information ◽  
High Resolution Power ◽  
Resolution Level ◽  
Health And Disease ◽  
High Doses ◽  
The Brain

The bidirectional microbiota–gut–brain axis has raised increasing interest over the past years in the context of health and disease, but there is a lack of information on molecular mechanisms underlying this connection. We hypothesized that change in microbiota composition may affect brain epigenetics leading to long-lasting effects on specific brain gene regulation. To test this hypothesis, we used Zebrafish (Danio Rerio) as a model system. As previously shown, treatment with high doses of probiotics can modulate behavior in Zebrafish, causing significant changes in the expression of some brain-relevant genes, such as BDNF and Tph1A. Using an ultra-deep targeted analysis, we investigated the methylation state of the BDNF and Tph1A promoter region in the brain and gut of probiotic-treated and untreated Zebrafishes. Thanks to the high resolution power of our analysis, we evaluated cell-to-cell methylation differences. At this resolution level, we found slight DNA methylation changes in probiotic-treated samples, likely related to a subgroup of brain and gut cells, and that specific DNA methylation signatures significantly correlated with specific behavioral scores.

scholarly journals The Microbiota–Gut–Brain Axis and Alzheimer Disease. From Dysbiosis to Neurodegeneration: Focus on the Central Nervous System Glial Cells

2021 ◽  
Vol 10 (11) ◽  
pp. 2358
Author(s):  
Maria Grazia Giovannini ◽  
Daniele Lana ◽  
Chiara Traini ◽  
Maria Giuliana Vannucchi
Keyword(s):  
Alzheimer Disease ◽  
Glial Cells ◽  
Cell Types ◽  
The Past ◽  
The Central Nervous System ◽  
Diseased State ◽  
The Brain ◽  
Alzheimer Disease Pathogenesis ◽  
Brain Homeostasis

The microbiota–gut system can be thought of as a single unit that interacts with the brain via the “two-way” microbiota–gut–brain axis. Through this axis, a constant interplay mediated by the several products originating from the microbiota guarantees the physiological development and shaping of the gut and the brain. In the present review will be described the modalities through which the microbiota and gut control each other, and the main microbiota products conditioning both local and brain homeostasis. Much evidence has accumulated over the past decade in favor of a significant association between dysbiosis, neuroinflammation and neurodegeneration. Presently, the pathogenetic mechanisms triggered by molecules produced by the altered microbiota, also responsible for the onset and evolution of Alzheimer disease, will be described. Our attention will be focused on the role of astrocytes and microglia. Numerous studies have progressively demonstrated how these glial cells are important to ensure an adequate environment for neuronal activity in healthy conditions. Furthermore, it is becoming evident how both cell types can mediate the onset of neuroinflammation and lead to neurodegeneration when subjected to pathological stimuli. Based on this information, the role of the major microbiota products in shifting the activation profiles of astrocytes and microglia from a healthy to a diseased state will be discussed, focusing on Alzheimer disease pathogenesis.

scholarly journals One Year of the COVID-19 Pandemic in Galicia: A Global View of Age-Group Statistics during Three Waves

2021 ◽  
Vol 18 (10) ◽  
pp. 5104
Author(s):  
Iván Area ◽  
Henrique Lorenzo ◽  
Pedro J. Marcos ◽  
Juan J. Nieto
Keyword(s):  
Intensive Care Unit ◽  
Hospital Admissions ◽  
Age Groups ◽  
Age Group ◽  
Nw Spain ◽  
The Past ◽  
Global View ◽  
Time Period ◽  
Key Variables ◽  
One Year

In this work we look at the past in order to analyze four key variables after one year of the COVID-19 pandemic in Galicia (NW Spain): new infected, hospital admissions, intensive care unit admissions and deceased. The analysis is presented by age group, comparing at each stage the percentage of the corresponding group with its representation in the society. The time period analyzed covers 1 March 2020 to 1 April 2021, and includes the influence of the B.1.1.7 lineage of COVID-19 which in April 2021 was behind 90% of new cases in Galicia. It is numerically shown how the pandemic affects the age groups 80+, 70+ and 60+, and therefore we give information about how the vaccination process could be scheduled and hints at why the pandemic had different effects in different territories.

Public Policy Administration

1985 ◽  
Vol 47 ◽  
pp. 1-16
Author(s):  
Richard A. Brumback
Keyword(s):  
Rhode Island ◽  
General Level ◽  
American Government ◽  
Introductory Course ◽  
The Past ◽  
Business Colleges ◽  
Business College ◽  
Large Numbers ◽  
The Subject ◽  
One Year

The teaching of an introductory course in American Government can be a difficult and frustrating endeavor under even the best of circumstances. Given the general level of cynicism and/or lack of interest by large numbers of Americans regarding politics and politicians, the task of generating student enthusiasm, or even mild interest, toward the subject matter can indeed be an arduous one. When the teaching of such a course takes place in a business college, and when the student audience is “captive” to a college requirement that all students must take the course, the task can be rendered considerably more formidable.For the past six years I have been teaching such courses at business colleges — one year at Bryant College in Rhode Island, and the following five years at Bentley College in Massachusetts.

scholarly journals Macrophages and microglia: the cerberus of glioblastoma

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Alice Buonfiglioli ◽  
Dolores Hambardzumyan
Keyword(s):  
Tumor Cells ◽  
Innate Immune System ◽  
Tumor Heterogeneity ◽  
Expression Profiles ◽  
Brain Parenchyma ◽  
Innate Immune ◽  
Malignant Growth ◽  
Neoplastic Cells ◽  
Functional Roles ◽  
The Brain

AbstractGlioblastoma (GBM) is the most aggressive and deadliest of the primary brain tumors, characterized by malignant growth, invasion into the brain parenchyma, and resistance to therapy. GBM is a heterogeneous disease characterized by high degrees of both inter- and intra-tumor heterogeneity. Another layer of complexity arises from the unique brain microenvironment in which GBM develops and grows. The GBM microenvironment consists of neoplastic and non-neoplastic cells. The most abundant non-neoplastic cells are those of the innate immune system, called tumor-associated macrophages (TAMs). TAMs constitute up to 40% of the tumor mass and consist of both brain-resident microglia and bone marrow-derived myeloid cells from the periphery. Although genetically stable, TAMs can change their expression profiles based upon the signals that they receive from tumor cells; therefore, heterogeneity in GBM creates heterogeneity in TAMs. By interacting with tumor cells and with the other non-neoplastic cells in the tumor microenvironment, TAMs promote tumor progression. Here, we review the origin, heterogeneity, and functional roles of TAMs. In addition, we discuss the prospects of therapeutically targeting TAMs alone or in combination with standard or newly-emerging GBM targeting therapies.

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