Multiple Myeloma DREAM Challenge reveals epigenetic regulator PHF19 as marker of aggressive disease.

While the past decade has seen meaningful improvements in clinical outcomes for multiple myeloma patients, a subset of patients does not benefit from current therapeutics for unclear reasons. Many gene expression-based models of risk have been developed, but each model uses a different combination of genes and often involves assaying many genes making them difficult to implement. We organized the Multiple Myeloma DREAM Challenge, a crowdsourced effort to develop models of rapid progression in newly diagnosed myeloma patients and to benchmark these against previously published models.

Questions and controversies in the study of time-varying functional connectivity in resting fMRI.

The brain is a complex, multiscale dynamical system composed of many interacting regions. Knowledge of the spatiotemporal organization of these interactions is critical for establishing a solid understanding of the brain's functional architecture and the relationship between neural dynamics and cognition in health and disease. The possibility of studying these dynamics through careful analysis of neuroimaging data has catalyzed substantial interest in methods that estimate time-resolved fluctuations in functional connectivity (often referred to as "dynamic" or time-varying functional connectivity; TVFC).

Integrative network modeling reveals mechanisms underlying T cell exhaustion.

Failure to clear antigens causes CD8 T cells to become increasingly hypo-functional, a state known as exhaustion. We combined manually extracted information from published literature with gene expression data from diverse model systems to infer a set of molecular regulatory interactions that underpin exhaustion. Topological analysis and simulation modeling of the network suggests CD8 T cells undergo 2 major transitions in state following stimulation.

Modifying Accelerometer Cut-Points Affects Criterion Validity in Simulated Free-Living for Adolescents and Adults.

: To assess changes in criterion validity when modifying cut-points for use in different epoch lengths. : Simulated free-living data came from 42 adolescents (2-hr each) and 29 adults (6-hr each) wearing a hip-worn accelerometer and portable indirect calorimeter (Cosmed K4b). K4b data were classified as sedentary behavior (SB), light physical activity (LPA), or moderate-to-vigorous physical activity (MVPA), and compared to estimates from accelerometer data processed with three youth and three adult cut-points in six epoch lengths (1, 5, 10, 15, 30, and 60-s).

A practical guide to methodological considerations in the controllability of structural brain networks.

Objective: Predicting how the brain can be driven to specific states by means of internal or external control requires a fundamental understanding of the relationship between neural connectivity and activity. Network control theory is a powerful tool from the physical and engineering sciences that can provide insights regarding that relationship; it formalizes the study of how the dynamics of a complex system can arise from its underlying structure of interconnected units.

Approach: Given the recent use of network control theory in neuroscience, it is now timely to offer a practical guide to methodological considerations in the controllability of structural brain networks.

Functional brain network architecture supporting the learning of social networks in humans.

Most humans have the good fortune to live their lives embedded in richly structured social groups. Yet, it remains unclear how humans acquire knowledge about these social structures to successfully navigate social relationships. Here we address this knowledge gap with an interdisciplinary neuroimaging study drawing on recent advances in network science and statistical learning.

Glucocerebrosidase Activity Modulates Neuronal Susceptibility to Pathological α-Synuclein Insult.

Mutations in the GBA1 gene are the most common genetic risk factor for Parkinson's disease (PD) and dementia with Lewy bodies (DLB). GBA1 encodes the lysosomal lipid hydrolase glucocerebrosidase (GCase), and its activity has been linked to accumulation of α-synuclein. The current study systematically examines the relationship between GCase activity and both pathogenic and non-pathogenic forms of α-synuclein in primary hippocampal, cortical, and midbrain neuron and astrocyte cultures, as well as in transgenic mice and a non-transgenic mouse model of PD.

Development of structure-function coupling in human brain networks during youth.

The protracted development of structural and functional brain connectivity within distributed association networks coincides with improvements in higher-order cognitive processes such as executive function. However, it remains unclear how white-matter architecture develops during youth to directly support coordinated neural activity. Here, we characterize the development of structure-function coupling using diffusion-weighted imaging and -back functional MRI data in a sample of 727 individuals (ages 8 to 23 y).

Disrupted basal ganglia-thalamocortical loops in focal to bilateral tonic-clonic seizures.

Focal to bilateral tonic-clonic seizures are associated with lower quality of life, higher risk of seizure-related injuries, increased chance of sudden unexpected death, and unfavourable treatment outcomes. Achieving greater understanding of their underlying circuitry offers better opportunity to control these seizures. Towards this goal, we provide a network science perspective of the interactive pathways among basal ganglia, thalamus and cortex, to explore the imprinting of secondary seizure generalization on the mesoscale brain network in temporal lobe epilepsy.

Emerging roles of network analysis for epilepsy.

In recent years there has been increasing interest in applying network science tools to EEG data. At the 2018 American Epilepsy Society conference in New Orleans, LA, the yearly session of the Engineering and Neurostimulation Special Interest Group focused on emerging, translational technologies to analyze seizure networks. Each speaker demonstrated practical examples of how network tools can be utilized in clinical care and provide additional data to help care for patients with intractable epilepsy.

Accuracy of the Cosmed K5 portable calorimeter.

Purpose: The purpose of this study was to assess the accuracy of the Cosmed K5 portable metabolic system dynamic mixing chamber (MC) and breath-by-breath (BxB) modes against the criterion Douglas bag (DB) method.

Methods: Fifteen participants (mean age±SD, 30.6±7.

Heritability and Cognitive Relevance of Structural Brain Controllability.

Cognition and behavior are thought to emerge from the connections and interactions among brain regions. The precise nature of these relationships remains elusive. Here we use tools provided by network control theory to determine how the structural connectivity profile of brain regions may shape individual variation in cognition.

Intersubject Synchronization of Late Adolescent Brain Responses to Violent Movies: A Virtue-Ethics Approach.

Movies that involve violence increasingly attract large audiences, leading to concern that such entertainment will encourage imitation by youth, especially when the violence is seen as justified. To assess differences between brain responses to justified and unjustified film violence, we computed intersubject correlation (ISC) of fMRI BOLD time courses in a sample of late adolescents while they watched pairs of movie segments featuring violent characters prior to and during violent action. Based on a virtue-ethics approach that emphasizes motives in moral evaluation, we hypothesized significant ISC in lateral orbital frontal cortex (lOFC) and ventromedial prefrontal cortex (vmPFC) in response to unjustified and justified scenes of movie violence, respectively.

Stability of spontaneous, correlated activity in mouse auditory cortex.

Neural systems can be modeled as complex networks in which neural elements are represented as nodes linked to one another through structural or functional connections. The resulting network can be analyzed using mathematical tools from network science and graph theory to quantify the system's topological organization and to better understand its function. Here, we used two-photon calcium imaging to record spontaneous activity from the same set of cells in mouse auditory cortex over the course of several weeks.

Within-person variability in sensation-seeking during daily life: Positive associations with alcohol use and self-defined risky behaviors.

Sensation-seeking is the seeking of varied, novel, and intense experiences and the willingness to take risks to engage in these experiences. Sensation-seeking is associated with engagement in risky behaviors but questions remain concerning the role of within-person variability in sensation-seeking. We use data from a 21-day daily diary from 167 participants (mean age = 25.

Genome-wide survey of cytochrome P450 genes in the salmon louse Lepeophtheirus salmonis (Krøyer, 1837).

Background: The salmon louse (Lepeophtheirus salmonis) infests farmed and wild salmonid fishes, causing considerable economic damage to the salmon farming industry. Infestations of farmed salmon are controlled using a combination of non-medicinal approaches and veterinary drug treatments. While L.

Critical and diverse roles of phosphates in human bone formation.

Humans utilise biomineralisation in the formation of bone and teeth. Human biomineralisation processes are defined by the transformation of an amorphous phosphate-based precursor to highly organised nanocrystals. Interestingly, ionic phosphate species not only provide a fundamental building block of biological mineral, but rather exhibit several diverse roles in mediating mineral formation in the physiological milieu.

Digital phenotyping for psychiatry: Accommodating data and theory with network science methodologies.

Digital phenotyping is the moment-by-moment quantification of our interactions with digital devices. With appropriate tools, digital phenotyping data afford unprecedented insight into our transactions with the world and hold promise for developing novel signatures of psychopathology that will aid in diagnosis, prognosis, and treatment selection of psychiatric disorders. In this review, we highlight empirical work merging digital phenotyping data, and particularly experience-sampling data collected via smartphone, with network theories of psychopathology and network science methodologies.

Switching antidepressants in the treatment of major depression: When, how and what to switch to?

Background: Switching antidepressant medications is recommended when an initial antidepressant is not effective, when it is unable to be tolerated or when there are significant drug interactions. The aim of this paper is to review the evidence regarding when to switch antidepressants and the optimal approach to switching.

Methods: Clinical and academic experts in mood disorders from Australia and New Zealand (Treatment Algorithm Group, TAG) met to discuss the key considerations regarding switching antidepressants in the treatment of depression and formulate recommendations about switching strategies.

Virtual resection predicts surgical outcome for drug-resistant epilepsy.

Patients with drug-resistant epilepsy often require surgery to become seizure-free. While laser ablation and implantable stimulation devices have lowered the morbidity of these procedures, seizure-free rates have not dramatically improved, particularly for patients without focal lesions. This is in part because it is often unclear where to intervene in these cases.

Repetitive negative thinking in daily life and functional connectivity among default mode, fronto-parietal, and salience networks.

Repetitive negative thinking (RNT) is a maladaptive response to sadness and a transdiagnostic risk-factor. A critical challenge hampering attempts to promote more adaptive responses to sadness is that the between-person characteristics associated with the tendency for RNT remain uncharacterized. From the perspective of the impaired disengagement hypothesis, we examine between-person differences in blood-oxygen-level-dependent (BOLD) functional networks underlying cognitive conflict signaling, self-referential thought, and cognitive flexibility, and the association between sadness and RNT in daily life.

Within-person variability in curiosity during daily life and associations with well-being.

Objective: Curiosity promotes engagement in novel situations and the accruement of resources that promote well-being. An open question is the extent to which curiosity lability, the degree to which curiosity fluctuates over short timescales, impacts well-being.

Method: We use data from a 21-day daily diary as well as trait measures in 167 participants (mean age = 25.

Unifying the Notions of Modularity and Core-Periphery Structure in Functional Brain Networks during Youth.

At rest, human brain functional networks display striking modular architecture in which coherent clusters of brain regions are activated. The modular account of brain function is pervasive, reliable, and reproducible. Yet, a complementary perspective posits a core-periphery or rich-club account of brain function, where hubs are densely interconnected with one another, allowing for integrative processing.