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Third-Generation Neuroimaging: Translating Research into Clinical Utility

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889450442 Year: Pages: 224 DOI: 10.3389/978-2-88945-044-2 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Psychiatry
Added to DOAB on : 2018-02-27 16:16:44
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Psychiatric imaging needs to move away from simple investigations of the neurobiology underling the early phases of psychiatric diseases to translate imaging findings in the clinical field targeting clinical outcomes including transition, remission and response to preventative interventions. This research topic aims to bring psychiatric neuroimaging studies towards translational impacts in clinical practice, suggesting that brain abnormalities may be of potential use for detecting clinical outcomes as treatment response. First-generation psychiatric neuroimaging focused on simple structural brain alterations associated with the neurobiology of the illness. These early studies adopted imaging methods mainly including computerized tomography (CT) to investigate brain size. Second-generation psychiatric neuroimaging studies benefited from more sophisticated techniques which included structural methods (sMRI) coupled with whole-brain automated methods (voxel based morphometry, VBM), white-matter methods (diffusion tensor imaging, DTI and tractography), functional methods (functional magnetic resonance imaging, fMRI) and advanced neurochemical imaging (PET techniques addressing receptor bindings and pre/post synaptic functions, magnetic resonance spectroscopy, MRS) and sophisticated meta-analytical imaging methods. However, no consistent or reliable anatomical or functional brain alterations have been univocally associated with any psychiatric disorder and no clinical applications have been developed in psychiatric neuroimaging. There is thus urgent need of psychiatric imaging to move towards third-generation paradigms. In this research topic, these novel neuroimaging studies here requested to move away from simple investigations of the neurobiology to translate imaging findings in the clinical field targeting longitudinal outcomes including transition, remission and response to preventative interventions. With respect to methods, the most recent neuroimaging approaches (e.g. structural and functional MRI, EEG, DTI, spectroscopy, PET) are welcome. Third generation psychiatric imaging studies including multimodal approaches, multi-center analyses, mega-analyses, effective connectivity, dynamic causal modelling, support vector machines, structural equation modelling, or graph theory analysis are highly appreciated. Furthermore, these third-generation imaging studies may benefit from the incorporation of new sources of neurobiological information such as whole genome sequencing, proteomic, lipidomic and expression profiles and cellular models derived from recent induced pluripotent stem cells research. We collect Original Research, Reviews, Mini-Reviews, Book Review, Clinical Case Study, Clinical Trial, Editorial, General Commentary, Hypothesis & Theory, Methods, Mini Opinion, Perspective, and Technology Report from international researcher and clinicians in this field. The purpose of this research topic is intended to provide the field with current third-generation neuroimaging approaches in translational psychiatry that is hoped to improve and create therapeutic options for psychiatric diseases.

Mental Imagery in Clinical Disorders

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889452620 Year: Pages: 106 DOI: 10.3389/978-2-88945-262-0 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Psychiatry
Added to DOAB on : 2018-02-27 16:16:44
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Mental imagery refers to the mental simulation or recreation of perceptual experience across different sensory modalities. The exploration of mental imagery represents a new and important area within clinical psychology, but arguably one still in its infancy. While mental imagery has featured prominently in recent theoretical accounts of disorders as diverse as post-traumatic stress disorder, phobia, body dysmorphic disorder, mood disorders, and psychosis, there remains an insufficiently strong theoretical and methodological foundation to enable comparison of the role of imagery across such different disorders. The current research topic presents a diverse range of cutting-edge papers focusing on investigating the underlying mechanisms and/or treatment interventions associated with mental imagery in clinical disorders, with the goal of helping establish those common elements most clinically relevant when investigating mental imagery. The research topic comprises fifteen articles drawn from the fields of psychiatry, psychology, and neuroscience. This is a unique collection of articles that combine different perspectives from the field of clinical psychology with more diverse perspectives drawn from the wider literature on mental imagery. The original research studies and theoretical articles presented are organised around four main chapters that cover imagery and eye movements, imagery and craving, imagery and autobiographical memory, and imagery and clinical disorders. We believe that the range of submissions presented in the research topic make a strong contribution to helping establish a theoretical and methodological foundation that can enable the effective study of imagery across different disorders and domains.

Data-Based Radiation Oncology - Design of Clinical Trials

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889454389 Year: Pages: 109 DOI: 10.3389/978-2-88945-438-9 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Oncology
Added to DOAB on : 2018-11-16 17:17:57
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In radiation oncology as in many other specialties clinical trials are essential to investigate new therapy approaches. Usually, preparation for a prospective clinical trial is extremely time consuming until ethics approval is obtained. To test a new treatment usually many years pass before it can be implemented in the routine care. During that time, already new interventions emerge, new drugs appear on the market, technical & physical innovations are being implemented, novel biology driven concepts are translated into clinical approaches while we are still investigating the ones from years ago. Another problem is associated with molecular diagnostics and the growing amount of tumor specific biomarkers which allows for a better stratification of patient subgroups. On the other side, this may result in a much longer time for patient recruiting and consequently in larger multicenter trials. Moreover, all of the relevant data must be readily available for treatment decision making, treatment as well as follow-up, and ultimately for trial evaluation. This challenges even more for agreed standards in data acquisition, quality and management. How could we change the way currently clinical trials are performed in a way they are safe and ethically justifiable and speed up the initiation process, so we can provide new and better treatments faster for our patients?Further, while we rely on various quantitative information handling distributed, large heterogeneous amounts of data efficiently is very important. Thus data management becomes a strong focus. A good infrastructure helps to plan, tailor and conduct clinical trials in a way they are easy and quickly analyzable.In this research topic we want to discuss new ideas for intelligent trial designs and concepts for data management.

Targeting PI3K/mTOR signaling in cancer

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889192441 Year: Pages: 93 DOI: 10.3389/978-2-88919-244-1 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Biology --- Medicine (General) --- Oncology
Added to DOAB on : 2015-11-16 15:44:59
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The phosphatidylinositol 3-kinase (PI3K)/mTOR pathway integrates signals from growth factors with nutrient signals and other conditions and controls multiple cell responses, including proliferation, survival and metabolism. Deregulation of the PI3K pathway has been extensively investigated in connection to cancer. Somatic or inherited mutations frequently occur in tumor suppressor genes (PTEN, TSC1/2, LKB1) and oncogenes (PIK3CA, PIK3R1, AKT) in the PI3K/mTOR pathway. The fact that the PI3K/mTOR pathway is deregulated in a large number of human malignancies, and its importance for different cellular responses, makes it an attractive drug target. Pharmacological PI3K inhibitors have played a very important role in studying cellular responses involving these enzymes. Currently, a wide range of selective PI3K inhibitors have been tested in preclinical studies and some have entered clinical trials in oncology. Rapamycin and its analogs targeting mTOR are effective in many preclinical cancer models. Although rapalogs are approved for the treatment of some cancers, their efficacy in clinical trials remains the subject of debate. Due to the complexity of the PI3K/mTOR signaling pathway, developing an effective anti-cancer therapy remains a challenge. The biggest challenge in curing cancer patients with various signaling pathway abnormalities is to target multiple components of different signal transduction pathways with mechanism-based combinatorial treatments.

Towards translating research to clinical practice: Novel Strategies for Discovery and Validation of Biomarkers for Brain Injury

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193912 Year: Pages: 178 DOI: 10.3389/978-2-88919-391-2 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Neurology
Added to DOAB on : 2015-12-03 13:02:24
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Traumatic brain injury (TBI) is a major cause of death and disability and one of the greatest unmet needs in medicine and public health. TBI not only has devastating effects on patients and their relatives but results in huge direct and indirect costs to society. Although guidelines for the management of patients have been developed and more than 200 clinical trials have been conducted, they have resulted in few improvements in clinical outcomes and no effective therapies approved for TBI. It is now apparent that the heterogeneity of clinical TBI is underlain by molecular phenotypes more complex and interactive than initially conceived and current approaches to the characterization, management and outcome prediction of TBI are antiquated, unidimensional and inadequate to capture the interindividual pathophysiological heterogeneity. Recent advances in proteomics and biomarker development provide unparalleled opportunities for unraveling substantial injury-specific and patient-specific variability and refining disease characterization. The identification of novel, sensitive, objective tools, referred to as biomarkers, can revolutionize pathophysiological insights, enable targeted therapies and personalized approaches to clinical management. In this Research Topic, we present novel approaches that provide an infrastructure for discovery and validation of new biomarkers of acute brain injury. These techniques include refined mass spectrometry technology and high throughput immunoblot techniques. Output from these approaches can identify potential candidate biomarkers employing systems biology and data mining methods. In this Research Topic, we present novel approaches that provide an infrastructure for discovery and validation of new biomarkers of acute brain injury. These techniques include refined mass spectrometry technology and high throughput immunoblot techniques. Output from these approaches can identify potential candidate biomarkers employing systems biology and data mining methods. Finally, suggestions are provided for the way forward, with an emphasis on need for a multidimensional approach that integrate a panel of pathobiologically diverse biomarkers with clinical variables and imaging-based assessments to improve diagnosis and classification of TBI and to develop best clinical practice guidelines.

New treatment perspectives in autism spectrum disorders

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195305 Year: Pages: 161 DOI: 10.3389/978-2-88919-530-5 Language: English
Publisher: Frontiers Media SA
Subject: Pediatrics --- Medicine (General)
Added to DOAB on : 2015-12-10 11:59:06
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Developing novel and more effective treatments that improve quality of life for individuals with autism spectrum disorders is urgently needed. To date a wide range of behavioral interventions have been shown to be safe and effective for improving language and cognition and adaptive behavior in children and adolescents with ASD. However many people with ASD can receive additional benefit from targeted pharmacological interventions. One of the major drawback in setting up therapeutics intervention is the remarkable individual differences found across individuals with ASD. As a matter of fact the medications that are currently available address only symptoms associated with ASD and not the core domains of social and communication dysfunction. The pathogenesis paradigm shift of ASD towards synaptic abnormalities moved the research to pathway to disease that involve multiple systems and that are becoming the forefront of ASD treatment and are pointing toward the development of new targeted treatments. Some new therapeutics have been tested and others are being studied. In this context single gene disorders frequently associated with ASD such as Rett Syndrome, Fragile X and Tuberous Sclerosis have been of significant aid as neurobiology of these disorders is more clear and has a potential to shed light on the altered signaling in ASD. However much research is needed to further understand the basic mechanisms of disease and the relationship to idiopathic ASD. Clinical trials in children are underway with agents directed to core symptoms and to the associated disorders in the search of new therapeutics and progress are expected with possible new option for therapeutics in ASD in the upcoming future. Children and Adolescents with ASD and their families can provide important information about their experience with new treatments and this should be a priority for future research. In addition, research performed on genetic mouse models of ASD will keep on providing useful information on the molecular pathways disrupted in the disease, thus contributing to identify novel drug targets.

When (and How) Is Theory of Mind Useful? Evidence from Life-Span Research

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889451012 Year: Pages: 182 DOI: 10.3389/978-2-88945-101-2 Language: English
Publisher: Frontiers Media SA
Subject: Psychology --- Science (General)
Added to DOAB on : 2017-07-06 13:27:36
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Theory of Mind (ToM) or mentalization is the ability to understand and foresee the behavior referring to one’s own and others’ mental states (Premack & Woodruff, 1978; Wimmer & Perner, 1983). This capacity, which is considered the most representative mechanism of social cognition, is a multifaceted set of competences liable to influence – and be influenced by – a manifold of psychosocial aspects. Studies on typical and atypical/clinical development during life showed that ToM is frequently delayed (e.g. in deafness) or impaired in many clinical conditions (e.g. Autism Spectrum Disorder, Attention Deficit Hyperactivity Disorder, Schizophrenia, Borderline Personality Disorder, Parkinson’s Disease, Alzheimer’s Disease) and, on the other hand, may not be unequivocally a positive experience. It is therefore possible to consider the existence of multiple kinds of Theory of Mind. In fact, ToM may vary along a quantitative and a qualitative continuum. As for the quantitative dimension, the continuum is constituted by the fluctuation between high and low levels of ToM ability in different clinical conditions. Along this continuum, impairment can mean “not enough” ToM (for example in Autism Spectrum Disorder) as well as “too much” ToM (for example in Schizophrenia and Borderline Personality Disorder). The qualitative dimension – highly interrelated with the quantitative one - regards the shift between adaptive (e.g. prosocial, nice ToM) vs. unadaptive (e.g. antisocial, nasty ToM) mental states content. The issue is discussed in light of recent evidence from outstanding researchers working on typical and atypical/clinical populations along the life-span. Findings from the fields of psychology, neuropsychology and neuroscience enrich the research topic argumentation.

Keywords

Theory of Mind --- typical --- clinical --- neural --- life-span

Application of Antigen Cross-Presentation Research into Patient Care

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889451913 Year: Pages: 124 DOI: 10.3389/978-2-88945-191-3 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2017-10-13 14:57:01
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The activation of adaptive immune responses requires the processing and presentation of protein antigens to lymphocytes. Especially dendritic cells are effective at display of antigen-derived peptides in the form of immunogenic peptide/MHC complexes to CD4 and CD8-positive T cells, and can stimulate even naive T cells to clonally expand. During the last 40 years, mechanisms that facilitate antigen processing and presentation were clarified, mostly from work in cell lines and mouse models. From mouse-based work, it is now clear that dendritic cells represent a collection of specialized cell subsets that are particularly well endowed to stimulate antigen transport to distinct tissue locations, to transfer antigens between cellular subsets or to trigger T cell responses. Dendritic cell subsets hold great promise for therapeutic application, for example as dendritic cell-based vaccines to bolster immune responses against viruses or malignant growths. Hurdles remain that preclude the efficient application of high quality pre-clinical research into standardized patient care. In this research topic, efforts in dendritic cell research and dendritic cell-based vaccines are discussed, from both pre-clinical and application points of view.

Mycoplasma pneumoniae Clinical Manifestations, Microbiology, and Immunology

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453627 Year: Pages: 175 DOI: 10.3389/978-2-88945-362-7 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Microbiology --- Medicine (General)
Added to DOAB on : 2018-02-27 16:16:45
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Mycoplasma pneumoniae (Mp) is a major human pathogen that causes both upper and lower respiratory infections, and is one of the leading causes of community acquired pneumonia (CAP), accounting for 11–15% of CAP throughout the world. Additionally it is known to induce an inflammatory process which depends on several mechanisms such as virulence of Mp (lipoproteins, community acquired respiratory distress syndrome (CARDS) toxin, oxidative products) and host defenses (cellular immunity and humoral immunity). Although it is a common pathogen, the pathogenesis for Mp infections is not yet fully understood. From the clinical point of view, since the pioneer studies in the 1960s and 1970s on the clinical presentation of Mp associated disease, the diagnostics approaches have changed dramatically leading to a better understanding of the clinical presentation and new issues have emerged - such as antibiotics resistance. The purpose of this Frontiers ebook is to thoroughly review and discuss the clinical presentation in view of the improved diagnostics, microbiological and immunological analysis of Mp infections, with focus on the history of Mp, clinical features of disease, bacterial structure of Mp and mechanism of gliding, clinical and laboratory diagnostics, the role of lipoproteins and Toll-like receptor, CARDS toxin, subtyping of Mp isolates and genome analysis, macrolide resistance and treatment.

Preclinical and clinical issues in Alzheimer's disease drug research and development

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194339 Year: Pages: 100 DOI: 10.3389/978-2-88919-433-9 Language: English
Publisher: Frontiers Media SA
Subject: Therapeutics --- Science (General)
Added to DOAB on : 2016-01-19 14:05:46
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Alzheimer’s disease (AD) is a chronic neurodegenerative disorder characterized by progressive cognitive dysfunction and memory loss, inability to perform the activities of daily living and mood disorders. According to the so-called “amyloid cascade hypothesis”, amyloid-ß- peptide (Aß), produced by beta- and gamma- secretase-mediated cleavages of the amyloid precursor protein (APP), plays a pivotal role in the pathogenesis of AD. Aß was also shown to contribute to AD pathology by stimulating the hyperphosphorylation of tau which is responsible for the formation of neurofibrillary tangles. However, the “amyloid cascade hypothesis” was challenged by other theories which lend support to the idea that Aß is not causative but can be considered as an “innocent bystander” in AD. Although preclinical research generated impressive lines of evidence about the several intracellular mechanism(s) whose impairment leads to the onset and progression of AD, clinical research aimed at the development of new drugs capable of preventing or delaying the onset of neuronal damage in AD patients has produced limited results. The drugs currently available for the treatment of AD are acetylcholinesterase inhibitors (AChEI) and the NMDA glutamate receptor antagonist memantine. The AChEI increase acetylcholine levels in the synaptic cleft, which are reduced because of the progressive damage of cholinergic neurons in cognitive brain areas (e.g. amygdala, hippocampus, and frontal cortex), whereas memantine is used to prevent/reduce calcium-dependent excitotoxic neuronal cell death. Both classes of drugs have been shown to improve symptoms related to cognitive decline, but their effects are confined largely to patients with mild to moderate AD, in particular during the first year or so of treatment. An alternative to this symptomatic treatments involves the use of drugs that intervene in the pathogenesis of the disease. Recently, monoclonal antibodies against Aß were proposed as novel agents capable to remove Aß from the brain thus preventing neuronal damage. The research topic focuses on the preclinical and clinical evidence about the several factors that contribute to the pathogenesis of AD as well as the potential therapeutic role of new classes of drugs still under preclinical or clinical development.

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