In a subset of patients, chronic exposure to stress is an etiological risk factor for neuroinflammation and depression. Neuroinflammation affects up to 27% of patients with MDD and is associated with ...a more severe, chronic, and treatment-resistant trajectory. Inflammation is not unique to depression and has transdiagnostic effects suggesting a shared etiological risk factor underlying psychopathologies and metabolic disorders. Research supports an association but not necessarily a causation with depression. Putative mechanisms link chronic stress to dysregulation of the HPA axis and immune cell glucocorticoid resistance resulting in hyperactivation of the peripheral immune system. The chronic extracellular release of DAMPs and immune cell DAMP-PRR signaling creates a feed forward loop that accelerates peripheral and central inflammation. Higher plasma levels of inflammatory cytokines, most consistently interleukin IL-1β, IL-6, and TNF-α, are correlated with greater depressive symptomatology. Cytokines sensitize the HPA axis, disrupt the negative feedback loop, and further propagate inflammatory reactions. Peripheral inflammation exacerbates central inflammation (neuroinflammation) through several mechanisms including disruption of the blood-brain barrier, immune cellular trafficking, and activation of glial cells. Activated glial cells release cytokines, chemokines, and reactive oxygen and nitrogen species into the extra-synaptic space dysregulating neurotransmitter systems, imbalancing the excitatory to inhibitory ratio, and disrupting neural circuitry plasticity and adaptation. In particular, microglial activation and toxicity plays a central role in the pathophysiology of neuroinflammation. Magnetic resonance imaging (MRI) studies most consistently show reduced hippocampal volumes. Neural circuitry dysfunction such as hypoactivation between the ventral striatum and the ventromedial prefrontal cortex underlies the melancholic phenotype of depression. Chronic administration of monoamine-based antidepressants counters the inflammatory response, but with a delayed therapeutic onset. Therapeutics targeting cell mediated immunity, generalized and specific inflammatory signaling pathways, and nitro-oxidative stress have enormous potential to advance the treatment landscape. Future clinical trials will need to include immune system perturbations as biomarker outcome measures to facilitate novel antidepressant development. In this overview, we explore the inflammatory correlates of depression and elucidate pathomechanisms to facilitate the development of novel biomarkers and therapeutics.
The advancement of precision medicine in medical care has led behind the conventional symptom-driven treatment process by allowing early risk prediction of disease through improved diagnostics and ...customization of more effective treatments. It is necessary to scrutinize overall patient data alongside broad factors to observe and differentiate between ill and relatively healthy people to take the most appropriate path toward precision medicine, resulting in an improved vision of biological indicators that can signal health changes. Precision and genomic medicine combined with artificial intelligence have the potential to improve patient healthcare. Patients with less common therapeutic responses or unique healthcare demands are using genomic medicine technologies. AI provides insights through advanced computation and inference, enabling the system to reason and learn while enhancing physician decision making. Many cell characteristics, including gene up-regulation, proteins binding to nucleic acids, and splicing, can be measured at high throughput and used as training objectives for predictive models. Researchers can create a new era of effective genomic medicine with the improved availability of a broad range of datasets and modern computer techniques such as machine learning. This review article has elucidated the contributions of ML algorithms in precision and genome medicine.
Gene set enrichment tests (a.k.a. functional enrichment analysis) are among the most frequently used methods in computational biology. Despite this popularity, there are concerns that these methods ...are being applied incorrectly and the results of some peer-reviewed publications are unreliable. These problems include the use of inappropriate background gene lists, lack of false discovery rate correction and lack of methodological detail. To ascertain the frequency of these issues in the literature, we performed a screen of 186 open-access research articles describing functional enrichment results. We find that 95% of analyses using over-representation tests did not implement an appropriate background gene list or did not describe this in the methods. Failure to perform p-value correction for multiple tests was identified in 43% of analyses. Many studies lacked detail in the methods section about the tools and gene sets used. An extension of this survey showed that these problems are not associated with journal or article level bibliometrics. Using seven independent RNA-seq datasets, we show misuse of enrichment tools alters results substantially. In conclusion, most published functional enrichment studies suffered from one or more major flaws, highlighting the need for stronger standards for enrichment analysis.
•A comprehensive review on the existing and emerging applications of ferrofluids.•Focus on machine element designing, bio-medical, and thermal engineering aspects.•Reports the gap areas till date in ...the above-mentioned applications.•The underlying physics of every application of ferrofluids is delineated.•An important platform for both researchers and industrial application engineers.
Ferrofluids are stable colloidal suspensions of nanometric sized ferromagnetic, or their oxide particles, in conventional basefluids like water, oil, etc. The property of ferromagnetism is changed to superparamagnetism by size reduction of the particles to nanometer level. It opens the possibility to tune the thermophysical properties of ferrofluids by the application of an external magnetic field. Ferrofluids were invented by Steve Papell of NASA in 1963 with the intention to make a suitable liquid rocket fuel which could be attracted by an external magnetic field towards the inlet of a pump in a zero-gravity environment. Subsequently, intense research has led to diverse applications of these fluids, from computer hard discs, clean room robots to dynamic loudspeakers, exploiting their unique operational behavior. Ferrofluid lubrication and film bearing have emerged as better alternatives to conventional systems. Contemporary times have also witnessed a plethora of bio-medical applications of ferrofluids, ranging from location-specific drug delivery, treatment of tumor cells, cell separation, tagging, and in diagnostic systems like Magnetic Resonance and Particle Imaging, to name a few. New vistas have opened in the context of thermal management of miniaturized systems. Ferrofluids, with enhanced thermal conductivity, and possibility of external control and manipulation of heat transfer coefficient, can potentially compete with other standard heat transfer solutions. In this background, this article attempts a comprehensive review of the gamut of existing and emerging applications of ferrofluids. Relevant insights of the underlying physics and transport mechanisms, which are harnessed in these applications, is also delineated.
Biopharmaceutics Classification System (BCS) Class II and IV drugs suffer from poor aqueous solubility and hence low bioavailability. Most of these drugs are hydrophobic and cannot be developed into ...a pharmaceutical formulation due to their poor aqueous solubility. One of the ways to enhance the aqueous solubility of poorlywater-soluble drugs is to use the principles of crystal engineering to formulate cocrystals of these molecules with water-soluble molecules (which are generally called coformers). Many researchers have shown that the cocrystals significantly enhance the aqueous solubility of poorly water-soluble drugs. In this review, we present a consolidated account of reports available in the literature related to the cocrystallization of poorly water-soluble drugs. The current practice to formulate new drug cocrystals with enhanced solubility involves a lot of empiricism. Therefore, in this work, attempts have been made to understand a general framework involved in successful (and unsuccessful) cocrystallization events which can yield different solid forms such as cocrystals, cocrystal polymorphs, cocrystal hydrates/solvates, salts, coamorphous solids, eutectics and solid solutions. The rationale behind screening suitable coformers for cocrystallization has been explained based on the rules of five i.e., hydrogen bonding, halogen bonding (and in general non-covalent bonding), length of carbon chain, molecular recognition points and coformer aqueous solubility. Different techniques to screen coformers for effective cocrystallization and methods to synthesize cocrystals have been discussed. Recent advances in technologies for continuous and solvent-free production of cocrystals have also been discussed. Furthermore, mechanisms involved in solubilization of these solid forms and the parameters influencing dissolution and stability of specific solid forms have been discussed. Overall, this review provides a consolidated account of the rationale for design of cocrystals, past efforts, recent developments and future perspectives for cocrystallization research which will be extremely useful for researchers working in pharmaceutical formulation development.
The recent approval of fungal carotenoids as food colorants by the European Union has strengthened the prospects for fungal cell factories for the production of polyketide pigments. Fungal production ...of colorants has the main advantage of making the manufacturer independent of the seasonal supply of raw materials, thus minimizing batch-to-batch variations. Here, we review the potential of polyketide pigments produced from chemotaxonomically selected non-toxigenic fungal strains (e.g. Penicillium and Epicoccum spp.) to serve as food colorants. We argue that the production of polyketide azaphilone pigments from such potentially safe hosts is advantageous over traditional processes that involve Monascus spp., which risks co-production of the mycotoxin citrinin. Thus, there is tremendous potential for the development of robust fungal production systems for polyketide pigments, both to tailor functionality and to expand the color palette of contemporary natural food colorants.
A coherent body of research recognizes the role of emotion in various aspects of consumer behavior. However, while a number of studies exist on the consequences of emotion, empirical investigations ...into its determinants in tourism have received lesser attention. Building on well-established cognitive appraisal theories of emotion, this study investigates the antecedents of tourists’ emotional responses toward destinations. Canonical correlation analysis supports an appraisal model of emotion in the context of tourist destinations. Results indicate that appraisals of pleasantness, goal congruence, and internal self-compatibility are the main determinants of joy, love, and positive surprise. Overall, the findings offer strategic marketing implications for tourist destinations.
Purpose
– The purpose of this paper is to attempt to provide a review of the growing literature on co-authorship networks and the research gaps that may be investigated for future studies in this ...field.
Design/methodology/approach
– The existing literature on co-authorship networks was identified, evaluated and interpreted. Narrative review style was followed.
Findings
– Co-authorship, a proxy of research collaboration, is a key mechanism that links different sets of talent to produce a research output. Co-authorship could also be seen from the perspective of social networks. An in-depth analysis of such knowledge networks provides an opportunity to investigate its structure. Patterns of these relationships could reveal, for example, the mechanism that shapes our scientific community. The study provides a review of the expanding literature on co-authorship networks.
Originality/value
– This is one of the first comprehensive reviews of network-based studies on co-authorship. The field is fast evolving, opening new gaps for potential research. The study identifies some of these gaps.
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