Identification and Characterization of Chemotherapy-Resistant High-Risk Neuroblastoma Persister Cells.

Relapse rates in high-risk neuroblastoma remain exceedingly high. The malignant cells that are responsible for relapse have not been identified, and mechanisms of therapy resistance remain poorly understood. In this study, we used single-nucleus RNA sequencing and bulk whole-genome sequencing to identify and characterize the residual malignant persister cells that survive chemotherapy from a cohort of 20 matched diagnosis and definitive surgery tumor samples from patients treated with high-risk neuroblastoma induction chemotherapy.

Hippocampal and medial prefrontal ensemble spiking represents episodes and rules in similar task spaces.

Episodic memory requires the hippocampus and prefrontal cortex to guide decisions by representing events in spatial, temporal, and personal contexts. Both brain regions have been described by cognitive theories that represent events in context as locations in maps or memory spaces. We query whether ensemble spiking in these regions described spatial structures as rats performed memory tasks.

Mitochondria dysregulation contributes to secondary neurodegeneration progression post-contusion injury in human 3D in vitro triculture brain tissue model.

Traumatic Brain injury-induced disturbances in mitochondrial fission-and-fusion dynamics have been linked to the onset and propagation of neuroinflammation and neurodegeneration. However, cell-type-specific contributions and crosstalk between neurons, microglia, and astrocytes in mitochondria-driven neurodegeneration after brain injury remain undefined. We developed a human three-dimensional in vitro triculture tissue model of a contusion injury composed of neurons, microglia, and astrocytes and examined the contributions of mitochondrial dysregulation to neuroinflammation and progression of injury-induced neurodegeneration.

Hippocampal and Medial Prefrontal Cortex Fractal Spiking Patterns Encode Episodes and Rules.

A central question in neuroscience is how the brain represents and processes information to guide behavior. The principles that organize brain computations are not fully known, and could include scale-free, or fractal patterns of neuronal activity. Scale-free brain activity may be a natural consequence of the relatively small subsets of neuronal populations that respond to task features, i.

Goal Choices Modify Frontotemporal Memory Representations.

Adapting flexibly to changing circumstances is guided by memory of past choices, their outcomes in similar circumstances, and a method for choosing among potential actions. The hippocampus (HPC) is needed to remember episodes, and the prefrontal cortex (PFC) helps guide memory retrieval. Single-unit activity in the HPC and PFC correlates with such cognitive functions.

Prehospital Naloxone Administration Patterns during the Era of Synthetic Opioids.

The opioid epidemic is an ongoing public health emergency, exacerbated in recent years by the introduction and rising prevalence of synthetic opioids. The was changed in 2017 to recommend allowing basic life support (BLS) clinicians to administer intranasal (IN) naloxone. This study examines local IN naloxone administration rates for 4 years after the new recommendation, and Glasgow Coma Scale (GCS) scores and respiratory rates before and after naloxone administration.

Predicting age and gender from network telemetry: Implications for privacy and impact on policy.

The systematic monitoring of private communications through the use of information technology pervades the digital age. One result of this is the potential availability of vast amount of data tracking the characteristics of mobile network users. Such data is becoming increasingly accessible for commercial use, while the accessibility of such data raises questions about the degree to which personal information can be protected.

Hippocampal signals modify orbitofrontal representations to learn new paths.

We often remember the consequences of past choices to adapt to changing circumstances. Recalling past events requires the hippocampus (HPC), and using stimuli to anticipate outcome values requires the orbitofrontal cortex (OFC). Spatial reversal tasks require both structures to navigate newly rewarded paths.

An Evaluation of Prehospital Adenosine Use.

Background: Adenosine has been safely used by paramedics for the treatment of stable supraventricular tachycardia since the mid-1990s. However, there continues to be variability in paramedics' ability to identify appropriate indications for adenosine administration. As the first of a planned series of studies aimed at improving the accuracy of SVT diagnosis and successful administration of adenosine by paramedics, this study details the current usage patterns of adenosine by paramedics.

EMS Non-Transport of Low-Risk COVID-19 Patients.

COVID-19 infections in the community have the potential to overwhelm both prehospital and in-hospital resources. Transport of well-appearing patients, in the absence of available emergency department treatment capacity, increases strain on the hospital and EMS system. In May of 2020, the Connecticut Office of EMS issued a voluntary, EMS-initiated, non-transport protocol for selected low-risk patients with symptoms consistent with COVID-19.

An in silico model for determining the influence of neuronal co-activity on rodent spatial behavior.

Background: Neuropsychological and neurophysiological analyses focus on understanding how neuronal activity and co-activity predict behavior. Experimental techniques allow for modulation of neuronal activity, but do not control neuronal ensemble spatiotemporal firing patterns, and there are few, if any, sophisticated in silico techniques which accurately reconstruct physiological neural spike trains and behavior using unit co-activity as an input parameter.

New Method: Our approach to simulation of neuronal spike trains is based on using state space modeling to estimate a weighted graph of interaction strengths between pairs of neurons along with separate estimations of spiking threshold voltage and neuronal membrane leakage.

Peripheral sensitization is demonstrated in subacromial pain syndrome, with central sensitization found only in females.

The objective of this study was to explore whether hypersensitivity in patients with subacromial pain syndrome (SPS) manifests purely as localized peripheral sensitization or central sensitization, is influenced by the presence of subacromial pain, and presents similarly in male and female patients. Pressure pain threshold was assessed in both a patient cohort with unilateral SPS and an uninjured matched control group. Control subjects were assessed twice, with a 15 minute rest period between testing, while patients were assessed at baseline and after an almost instantaneous reduction in pain arising from an anesthetic injection in patients.

Weakness in patients with subacromial pain syndrome is local and more pronounced in females.

Background: Subacromial pain syndrome is the predominant cause of shoulder pain, accounting for approximately half of all shoulder complaints. This population presents with weakness of the involved shoulder. However, there is a gap in our understanding of how pain contributes to this weakness, and whether there are sex related differences.

Does precise case disclosure limit precautionary behavior? Evidence from COVID-19 in Singapore.

Limiting the spread of contagious diseases can involve both government-managed and voluntary efforts. Governments have a number of policy options beyond direct intervention that can shape individuals' responses to a pandemic and its associated costs. During its first wave of COVID-19 cases, Singapore was among a few countries that attempted to adjust behavior through the announcement of detailed case information.

Post-error recruitment of frontal sensory cortical projections promotes attention in mice.

The frontal cortex, especially the anterior cingulate cortex area (ACA), is essential for exerting cognitive control after errors, but the mechanisms that enable modulation of attention to improve performance after errors are poorly understood. Here we demonstrate that during a mouse visual attention task, ACA neurons projecting to the visual cortex (VIS; ACA neurons) are recruited selectively by recent errors. Optogenetic manipulations of this pathway collectively support the model that rhythmic modulation of ACA neurons in anticipation of visual stimuli is crucial for adjusting performance following errors.

Heterogeneity in Expectations, Risk Tolerance, and Household Stock Shares: The Attenuation Puzzle.

This paper jointly estimates the relationship between stock share and expectations and risk preferences. The survey allows individual-level, quantitative estimates of risk tolerance and of the perceived mean and variance of stock returns. These estimates have economically and statistically significant association for the distribution of stock shares with relative magnitudes in proportion with the predictions of theories.

Flexible spatial learning requires both the dorsal and ventral hippocampus and their functional interactions with the prefrontal cortex.

When faced with changing contingencies, animals can use memory to flexibly guide actions, engaging both frontal and temporal lobe brain structures. Damage to the hippocampus (HPC) impairs episodic memory, and damage to the prefrontal cortex (PFC) impairs cognitive flexibility, but the circuit mechanisms by which these areas support flexible memory processing remain unclear. The present study investigated these mechanisms by temporarily inactivating the medial PFC (mPFC), the dorsal HPC (dHPC), and the ventral HPC (vHPC), individually and in combination, as rats learned spatial discriminations and reversals in a plus maze.

The nucleus reuniens of the thalamus sits at the nexus of a hippocampus and medial prefrontal cortex circuit enabling memory and behavior.

The nucleus reuniens of the thalamus (RE) is a key component of an extensive network of hippocampal and cortical structures and is a fundamental substrate for cognition. A common misconception is that RE is a simple relay structure. Instead, a better conceptualization is that RE is a critical component of a canonical higher-order cortico-thalamo-cortical circuit that supports communication between the medial prefrontal cortex (mPFC) and the hippocampus (HC).

Howard B. Eichenbaum (1947-2017).

Presents an obituary of Howard B. Eichenbaum (1947-2017). Eichenbaum, a world leader in the study of memory and the brain, died in Boston, Massachusetts, on July 21, 2017, at age 69, following recent spine surgery.

Subacromial Anesthetics Increase Proprioceptive Deficit in the Shoulder and Elbow in Patients With Subacromial Impingement Syndrome.

Shoulder proprioception gives information regarding arm joint position and movement direction. Several studies have investigated shoulder proprioceptive acuity in patients with subacromial impingement syndrome (SIS); however, differences in protocols and between-subjects designs have limited scientific inferences regarding proprioception and SIS. We aimed to determine within-subject differences in shoulder and elbow proprioceptive acuity in 17 patients with stage 2 SIS following treatment of a local anesthetic injection.

Medial Prefrontal Cortex Reduces Memory Interference by Modifying Hippocampal Encoding.

The prefrontal cortex (PFC) is crucial for accurate memory performance when prior knowledge interferes with new learning, but the mechanisms that minimize proactive interference are unknown. To investigate these, we assessed the influence of medial PFC (mPFC) activity on spatial learning and hippocampal coding in a plus maze task that requires both structures. mPFC inactivation did not impair spatial learning or retrieval per se, but impaired the ability to follow changing spatial rules.

Partial lesion of the nigrostriatal dopamine pathway in rats impairs egocentric learning but not spatial learning or behavioral flexibility.

Degeneration of the nigrostriatal dopaminergic system in Parkinson's disease (PD) causes motor dysfunction and cognitive impairment, but the etiology of the cognitive deficits remains unclear. The present study investigated the behavioral effects of partial lesions of the nigrostriatal dopamine (DA) pathway. Rats received bilateral infusions of either 6-hydroxydopamine (6-OHDA) or vehicle into the dorsolateral striatum and were tested in spatial and procedural learning tasks.

Oxytocin improves behavioral and electrophysiological deficits in a novel Shank3-deficient rat.

Mutations in the synaptic gene lead to a neurodevelopmental disorder known as Phelan-McDermid syndrome (PMS). PMS is a relatively common monogenic and highly penetrant cause of autism spectrum disorder (ASD) and intellectual disability (ID), and frequently presents with attention deficits. The underlying neurobiology of PMS is not fully known and pharmacological treatments for core symptoms do not exist.