ResearchPad - perspective-article https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Structured assessment of frailty in multiple myeloma as a paradigm of individualized treatment algorithms in cancer patients at advanced age]]> https://www.researchpad.co/article/elastic_article_11046 <![CDATA[Commentary on Ferguson, et al., “Impact of Non-pharmaceutical Interventions (NPIs) to Reduce COVID-19 Mortality and Healthcare Demand”]]> https://www.researchpad.co/article/N21d7ecf2-94f8-4d6d-998d-4730b7cba071

A recent manuscript (Ferguson et al. in Impact of non-pharmaceutical interventions (NPIs) to reduce COVID-19 mortality and healthcare demand, Imperial College COVID-19 Response Team, London, 2020. https://www.imperial.ac.uk/media/imperial-college/medicine/sph/ide/gida-fellowships/Imperial-College-COVID19-NPI-modelling-16-03-2020.pdf) from Imperial College modelers examining ways to mitigate and control the spread of COVID-19 has attracted much attention. In this paper, we will discuss a coarse taxonomy of models and explore the context and significance of the Imperial College and other models in contributing to the analysis of COVID-19.

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<![CDATA[Close Encounters of the Cell Kind: The Impact of Contact Inhibition on Tumour Growth and Cancer Models]]> https://www.researchpad.co/article/Nec7bdc7e-d845-4f56-b7e8-b0e484b98d88

Cancer is a complex phenomenon, and the sheer variation in behaviour across different types renders it difficult to ascertain underlying biological mechanisms. Experimental approaches frequently yield conflicting results for myriad reasons, and mathematical modelling of cancer is a vital tool to explore what we cannot readily measure, and ultimately improve treatment and prognosis. Like experiments, models are underpinned by certain biological assumptions, variation of which can lead to divergent predictions. An outstanding and important question concerns contact inhibition of proliferation (CIP), the observation that proliferation ceases when cells are spatially confined by their neighbours. CIP is a characteristic of many healthy adult tissues, but it remains unclear to which extent it holds in solid tumours, which exhibit regions of hyper-proliferation, and apparent breakdown of CIP. What precisely occurs in tumour tissue remains an open question, which mathematical modelling can help shed light on. In this perspective piece, we explore the implications of different hypotheses and available experimental evidence to elucidate the implications of these scenarios. We also outline how erroneous conclusions about the nature of tumour growth may be arrived at by looking selectively at biological data in isolation, and how this might be circumvented.

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<![CDATA[Is caries an independent risk factor for the child’s psychomotor development? - A new insight to potentially shed the underlying mechanisms]]> https://www.researchpad.co/article/5c9e5419d5eed0c48423a1d3 ]]> <![CDATA[Lab-on-a-Tip (LOT): Where Nanotechnology Can Revolutionize Fibre Optics]]> https://www.researchpad.co/article/5c03e665d5eed0c48461000f

Recently developed lab-on-a-chip technologies integrate multiple traditional assays on a single chip with higher sensitivity, faster assay time, and more streamlined sample operation. We discuss the prospects of the lab-on-a-tip platform, where assays can be integrated on a miniaturized tip for in situ and in vivo analysis. It will resolve some of the limitations of available lab-on-a-chip platforms and enable next generation multifunctional in vivo sensors, as well as analytical techniques at the single cell or even sub-cellular levels.

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<![CDATA[Male or Female? Brains are Intersex]]> https://www.researchpad.co/article/5989da27ab0ee8fa60b812c1

The underlying assumption in popular and scientific publications on sex differences in the brain is that human brains can take one of two forms “male” or “female,” and that the differences between these two forms underlie differences between men and women in personality, cognition, emotion, and behavior. Documented sex differences in brain structure are typically taken to support this dimorphic view of the brain. However, neuroanatomical data reveal that sex interacts with other factors in utero and throughout life to determine the structure of the brain, and that because these interactions are complex, the result is a multi-morphic, rather than a dimorphic, brain. More specifically, here I argue that human brains are composed of an ever-changing heterogeneous mosaic of “male” and “female” brain characteristics (rather than being all “male” or all “female”) that cannot be aligned on a continuum between a “male brain” and a “female brain.” I further suggest that sex differences in the direction of change in the brain mosaic following specific environmental events lead to sex differences in neuropsychiatric disorders.

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<![CDATA[Selectivity and Specificity of Sphingosine-1-Phosphate Receptor Ligands: Caveats and Critical Thinking in Characterizing Receptor-Mediated Effects]]> https://www.researchpad.co/article/5989da78ab0ee8fa60b976c3

Receptors for sphingosine-1-phosphate (S1P) have been identified only recently. Their medicinal chemistry is therefore still in its infancy, and few selective agonists or antagonists are available. Furthermore, the selectivity of S1P receptor agonists or antagonists is not well established. JTE-013 and BML-241 (also known as CAY10444), used extensively as specific S1P2 and S1P3 receptors antagonists respectively, are cases in point. When analyzing S1P-induced vasoconstriction in mouse basilar artery, we observed that JTE-013 inhibited not only the effect of S1P, but also the effect of U46619, endothelin-1 or high KCl; JTE-013 strongly inhibited responses to S1P in S1P2 receptor knockout mice. Similarly, BML-241 has been shown to inhibit increases in intracellular Ca2+ concentration via P2 receptor or α1A-adrenoceptor stimulation and α1A-adrenoceptor-mediated contraction of rat mesenteric artery, while it did not affect S1P3-mediated decrease of forskolin-induced cyclic AMP accumulation. Another putative S1P1/3 receptor antagonist, VPC23019, does not inhibit S1P3-mediated vasoconstriction. With these examples in mind, we discuss caveats about relying on available pharmacological tools to characterize receptor subtypes.

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<![CDATA[Systems pharmacology approaches for optimization of antiangiogenic therapies: challenges and opportunities]]> https://www.researchpad.co/article/5989da7fab0ee8fa60b9a184

Targeted therapies have become an important therapeutic paradigm for multiple malignancies. The rapid development of resistance to these therapies impedes the successful management of advanced cancer. Due to the redundancy in angiogenic signaling, alternative proangiogenic factors are activated upon treatment with anti-VEGF agents. Higher doses of the agents lead to greater stimulation of compensatory proangiogenic pathways that limit the therapeutic efficacy of VEGF-targeted drugs and produce escape mechanisms for tumor. Evidence suggests that dose intensity and schedules affect the dynamics of the development of this resistance. Thus, an optimal dosing regimen is crucial to maximizing the therapeutic benefit of antiangiogenic agents and limiting treatment resistance. A systems pharmacology approach using multiscale computational modeling can facilitate a mechanistic understanding of these dynamics of angiogenic biomarkers and their impacts on tumor reduction and resistance. Herein, we discuss a systems pharmacology approach integrating the biology of VEGF-targeted therapy resistance, including circulating biomarkers, and pharmacodynamics to enable the optimization of antiangiogenic therapy for therapeutic gains.

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<![CDATA[Revisiting the Role of Neurons in Neurovascular Coupling]]> https://www.researchpad.co/article/5989db18ab0ee8fa60bcd803

In this article, we will review molecular, anatomical, physiological and pharmacological data in an attempt to better understand how excitatory and inhibitory neurons recruited by distinct afferent inputs to the cerebral cortex contribute to the coupled hemodynamic response, and how astrocytes can act as intermediaries to these neuronal populations. We aim at providing the pros and cons to the following statements that, depending on the nature of the afferent input to the neocortex, (i) different neuronal or astroglial messengers, likely acting in sequence, mediate the hemodynamic changes, (ii) some recruited neurons release messengers that directly alter blood vessel tone, (iii) others act by modulating neuronal and astroglial activity, and (iv) astrocytes act as intermediaries for both excitatory and inhibitory neurotransmitters. We will stress that a given afferent signal activates a precise neuronal circuitry that determines the mediators of the hemodynamic response as well as the level of interaction with surrounding astrocytes.

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<![CDATA[Affective coding: the emotional dimension of agency]]> https://www.researchpad.co/article/5989d9dbab0ee8fa60b67b1c

The sense of agency (SoA) (i.e., the registration that I am the initiator and controller of my actions and relevant events) is associated with several affective dimensions. This makes it surprising that the emotion factor has been largely neglected in the field of agency research. Current empirical investigations of the SoA mainly focus on sensorimotor signals (i.e., efference copy) and cognitive cues (i.e., intentions, beliefs) and on how they are integrated. Here we argue that this picture is not sufficient to explain agency experience, since agency and emotions constantly interact in our daily life by several ways. Reviewing first recent empirical evidence, we show that self-action perception is in fact modulated by the affective valence of outcomes already at the sensorimotor level. We hypothesize that the “affective coding” between agency and action outcomes plays an essential role in agency processing, i.e., the prospective, immediate or retrospective shaping of agency representations by affective components. This affective coding of agency be differentially altered in various neuropsychiatric diseases (e.g., schizophrenia vs. depression), thus helping to explain the dysfunctions and content of agency experiences in these diseases.

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<![CDATA[Hierarchy of Idea-Guided Action and Perception-Guided Movement]]> https://www.researchpad.co/article/5989d9dfab0ee8fa60b68f88

The ideomotor theory of voluntary behavior assumes that the selection and control of a concrete goal-directed movement depends on imagining its direct perceptual consequences. However, this perception-guided assumption neglects the fact that behavioral control entails a hierarchical mechanism wherein conceptual expectations – action goals – can modulate lower level perceptuo-motor representations. In this paper, we focus on the hierarchical nature of voluntary behavior by distinguishing between perceptual representations of images that relate to attainment of concrete movement goals and conceptual representations of ideas that pertain to attainment of action goals. We review the dominant ideomotor principle of the direct perceptuo-motor relation and examine its limitation in the light of the proposed hierarchical view of voluntary behavior. Finally, we offer a revision of the ideomotor principle that allows extension of its explanatory domain from perception-guided movement to conceptual, idea-guided action.

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<![CDATA[Beyond the Antigen Receptor: Editing the Genome of T-Cells for Cancer Adoptive Cellular Therapies]]> https://www.researchpad.co/article/5989db05ab0ee8fa60bc7ef0

Recent early stage clinical trials evaluating the adoptive transfer of patient CD8+ T-cells re-directed with antigen receptors recognizing tumors have shown very encouraging results. These reports provide strong support for further development of the therapeutic concept as a curative cancer treatment. In this respect combining the adoptive transfer of tumor-specific T-cells with therapies that increase their anti-tumor capacity is viewed as a promising strategy to improve treatment outcome. The ex vivo genetic engineering step that underlies T-cell re-direction offers a unique angle to combine antigen receptor delivery with the targeting of cell-intrinsic pathways that restrict T-cell effector functions. Recent progress in genome editing technologies such as protein- and RNA-guided endonucleases raise the possibility of disrupting gene expression in T-cells in order to enhance effector functions or to bypass tumor immune suppression. This approach would avoid the systemic administration of compounds that disrupt immune homeostasis, potentially avoiding autoimmune adverse effects, and could improve the efficacy of T-cell based adoptive therapies.

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<![CDATA[Is integration and survival of newborn neurons the bottleneck for effective neural repair by endogenous neural precursor cells?]]> https://www.researchpad.co/article/5989d9e1ab0ee8fa60b69a5b

After two decades of research the existence of adult neural precursor cells and the phenomenon of adult neurogenesis is well established. However, there has been little or no effective harnessing of these endogenous cells to promote functional neuronal replacement following neural injury or disease. Neural precursor cells can respond to neural damage by proliferating, migrating to the site of injury, and differentiating into neuronal or glial lineages. However, after a month or so, very few or no newborn neurons can be detected, suggesting that even though neuroblasts are generated, they generally fail to survive as mature neurons and contribute to the local circuitry. Is this lack of survival and integration one of the major bottlenecks that inhibits effective neuronal replacement and subsequent repair of the nervous system following injury or disease? In this perspective article the possibility that this bottleneck can be targeted to enhance the integration and subsequent survival of newborn neurons will be explored and will suggest some possible mechanisms that may need to be modulated for this to occur.

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<![CDATA[We're the Same… but Different: Addressing Academic Divides in the Study of Brain and Behavior]]> https://www.researchpad.co/article/5989db24ab0ee8fa60bcfe8a

How the brain mediates behavior is a question relevant to a broad range of disciplines including evolutionary biology, basic neuroscience, psychiatry, and population health. Experiments in animals have traditionally used two distinct approaches to explore brain–behavior relationships; one uses naturally existing behavioral models while the other focuses on the creation and investigation of medically oriented models using existing laboratory-amenable organisms. Scientists using the first approach are often referred to and self identify as “neuroethologists,” while the second category spans a variety of other sub-disciplines but is often referred to broadly as “behavioral neuroscience.” Despite an overall common scientific goal – the elucidation of the neural basis of behavior – members of these two groups often come from different scientific lineages, seek different sources of funding, and make their homes in different departments or colleges. The separation of these groups is also fostered by their attendance at different scientific conferences and publication records that reflect different journal preferences. Bridging this divide represents an opportunity to explore previously unanswerable questions and foster rapid scientific advances. This article explores the reasons for this divide and proposes measures that could help increase technology transfer and communication between these groups, potentially overcoming both physical and ideological gaps.

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<![CDATA[Setting the Stage: Measure Selection, Coordination, and Data Collection for a National Self-Management Initiative]]> https://www.researchpad.co/article/5989da04ab0ee8fa60b752dc

This paper describes the history and rationale behind the development of a centralized data collection system for the national rollout of the Chronic Disease Self-Management Program (CDSMP) through the American Recovery and Reinvestment Act of 2009 Communities Putting Prevention to Work: CDSMP initiative. In addition to justifying the need for solutions to the burgeoning burden of chronic disease in the United States, this paper provides details about CDSMP and related self-management education programs, including their structure, facilitator training, and effectiveness. These topics set the stage for the processes and procedures to create and manage the database for use at the national, state, and local levels. Furthermore, this paper describes the processes related to selecting variables, coordinating data collection, and utilizing data to inform research and policy.

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<![CDATA[Meanings, Mechanisms, and Measures of Holistic Processing]]> https://www.researchpad.co/article/5989dad7ab0ee8fa60bb85d0

Few concepts are more central to the study of face recognition than holistic processing. Progress toward understanding holistic processing is challenging because the term “holistic” has many meanings, with different researchers addressing different mechanisms and favoring different measures. While in principle the use of different measures should provide converging evidence for a common theoretical construct, convergence has been slow to emerge. We explore why this is the case. One challenge is that “holistic processing” is often used to describe both a theoretical construct and a measured effect, which may not have a one-to-one mapping. Progress requires more than greater precision in terminology regarding different measures of holistic processing or different hypothesized mechanisms of holistic processing. Researchers also need to be explicit about what meaning of holistic processing they are investigating so that it is clear whether different researchers are describing the same phenomenon or not. Face recognition differs from object recognition, and not all meanings of holistic processing are equally suited to help us understand that important difference.

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<![CDATA[Redefining neuromarketing as an integrated science of influence]]> https://www.researchpad.co/article/5989da5aab0ee8fa60b8fc51

Multiple transformative forces target marketing, many of which derive from new technologies that allow us to sample thinking in real time (i.e., brain imaging), or to look at large aggregations of decisions (i.e., big data). There has been an inclination to refer to the intersection of these technologies with the general topic of marketing as “neuromarketing”. There has not been a serious effort to frame neuromarketing, which is the goal of this paper. Neuromarketing can be compared to neuroeconomics, wherein neuroeconomics is generally focused on how individuals make “choices”, and represent distributions of choices. Neuromarketing, in contrast, focuses on how a distribution of choices can be shifted or “influenced”, which can occur at multiple “scales” of behavior (e.g., individual, group, or market/society). Given influence can affect choice through many cognitive modalities, and not just that of valuation of choice options, a science of influence also implies a need to develop a model of cognitive function integrating attention, memory, and reward/aversion function. The paper concludes with a brief description of three domains of neuromarketing application for studying influence, and their caveats.

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<![CDATA[The Conversion of a Practice-Based Lifestyle Enhancement Program into a Formalized, Testable Program: From Texercise Classic to Texercise Select]]> https://www.researchpad.co/article/5989db39ab0ee8fa60bd4306

Little is known about the structure, content, and benefits of practice-based or grass roots health programs that have been widely delivered by a variety of community organizations and stakeholders. This perspective will document the natural history of Texercise Classic, a state-endorsed but previously untested lifestyle health promotion program. It will: (1) discuss Texercise Classic’s participant reach and adoption over time; (2) describe the rationale and processes employed to formalize Texercise Classic into a more structured program known as Texercise Select; (3) outline the essential elements and activities included in Texercise Select and contrast them with those included in Texercise Classic; and (4) highlight key components for uniform facilitator training. The discussion will reflect upon the evolution of Texercise, compare and contrast the benefits and challenges of each program, and review the “next steps” for Texercise Select. In contrasting Texercise Classic and Select, it is important to understand the benefits and challenges of both programs. Preliminary results indicate that Texercise Select is effective, yet its ability to sustain the same reach as Texercise Classic remains unknown and an area for future study.

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<![CDATA[New insights into the role of histamine in subventricular zone-olfactory bulb neurogenesis]]> https://www.researchpad.co/article/5989daceab0ee8fa60bb54ad

The subventricular zone (SVZ) contains neural stem cells (NSCs) that generate new neurons throughout life. Many brain diseases stimulate NSCs proliferation, neuronal differentiation and homing of these newborns cells into damaged regions. However, complete cell replacement has never been fully achieved. Hence, the identification of proneurogenic factors crucial for stem cell-based therapies will have an impact in brain repair. Histamine, a neurotransmitter and immune mediator, has been recently described to modulate proliferation and commitment of NSCs. Histamine levels are increased in the brain parenchyma and at the cerebrospinal fluid (CSF) upon inflammation and brain injury, thus being able to modulate neurogenesis. Herein, we add new data showing that in vivo administration of histamine in the lateral ventricles has a potent proneurogenic effect, increasing the production of new neuroblasts in the SVZ that ultimately reach the olfactory bulb (OB). This report emphasizes the multidimensional effects of histamine in the modulation of NSCs dynamics and sheds light into the promising therapeutic role of histamine for brain regenerative medicine.

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<![CDATA[Attention mechanisms and the mosaic evolution of speech]]> https://www.researchpad.co/article/5989daa8ab0ee8fa60ba8690

There is still no categorical answer as to why humans, and no other species, have speech, or why speech is the way it is. Several purely anatomical arguments have been put forward, but they have been shown to be false, biologically implausible, or of limited scope. This perspective paper supports the idea that evolutionary theories of speech could benefit from a focus on the cognitive mechanisms that make speech possible, for which antecedents in evolutionary history and brain correlates can be found. This type of approach is part of a very recent but rapidly growing trend that has already provided crucial insights on the nature of human speech by focusing on the biological bases of vocal learning. Here we contend that a general mechanism of attention, which manifests itself not only in the visual but also in the auditory modality, might be one of the key ingredients of human speech, in addition to the mechanisms underlying vocal learning, and the pairing of facial gestures with vocalic units.

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