Bayesian Estimation Improves Prediction of Outcomes after Epilepsy Surgery.

Low power is a problem in many fields, as underpowered studies that find a statistically significant result will exaggerate the magnitude of the observed effect size. We quantified the statistical power and magnitude error of studies of epilepsy surgery outcomes. The median power across all studies was 14%. Studies with a median sample size or less (n<=56) and a statistically significant result exaggerated the true effect size by a factor of 5.4 (median odds ratio 9.3 vs. median true odds ratio 1.7), while the Bayesian estimate of the odds ratio only exaggerated the true effect size by a factor of 1.6 (2.7 vs. 1.7). We conclude that Bayesian estimation of odds ratio attenuates the exaggeration of significant effect sizes in underpowered studies. This approach could help improve patient counseling about the chance of seizure freedom after epilepsy surgery.

Differential vulnerability of anterior cingulate cortex cell types to diseases and drugs.

In psychiatric disorders, mismatches between disease states and therapeutic strategies are highly pronounced, largely because of unanswered questions regarding specific vulnerabilities of different cell types and therapeutic responses. Which cellular events (housekeeping or salient) are most affected? Which cell types succumb first to challenges, and which exhibit the strongest response to drugs? Are these events coordinated between cell types? How does disease and drug effect this coordination? To address these questions, we analyzed single-nucleus-RNAseq (sn-RNAseq) data from the human anterior cingulate cortex-a region involved in many psychiatric disorders. Density index, a metric for quantifying similarities and dissimilarities across functional profiles, was employed to identify common or salient functional themes across cell types. Cell-specific signatures were integrated with existing disease and drug-specific signatures to determine cell-type-specific vulnerabilities, druggabilities, and responsiveness. Clustering of functional profiles revealed cell types jointly participating in these events. SST and VIP interneurons were found to be most vulnerable, whereas pyramidal neurons were least. Overall, the disease state is superficial layer-centric, influences cell-specific salient themes, strongly impacts disinhibitory neurons, and influences astrocyte interaction with a subset of deep-layer pyramidal neurons. In absence of disease, drugs profiles largely recapitulate disease profiles, offering a possible explanation for drug side effects. However, in presence of disease, drug activities, are deep layer-centric and involve activating a distinct subset of deep-layer pyramidal neurons to circumvent the disease state's disinhibitory circuit malfunction. These findings demonstrate a novel application of sn-RNAseq data to explain drug and disease action at a systems level.

Integrating single-cell transcriptomics and microcircuit computer modeling.

Biophysically realistic computer modeling of neuronal microcircuitry has served as a testing ground for hypotheses related to the structure and function of different brain microcircuits. Recent advances in single-cell transcriptomics provide snapshots of a neuron's molecular state and have demonstrated that cell-specific genetic markers engineer the electrophysiological properties of a neuron. Integrating these molecular details with biophysical modeling can allow unprecedented mechanistic insights. In this opinion review, we consider systems biology-based strategies involving statistical deconvolution and gene ontology to integrate the two approaches. We foresee that this integration will infer the nonlinear interactions between the transcriptomically detailed neurons in different brain states. For an initial assessment of these integrative strategies, we recommend testing them on a penetrant phenotype such as epilepsy or a basic organism model such as Caenorhabditis elegans.

Increasing hemoglobin concentration with an artificial oxygen carrier improves severe anemia-induced degraded cognitive function.

ABSTRACT: Before death, patients commonly experience impaired consciousness for a significant period, frequently preventing family and others from final interactions with the patient. Some of these episodes of cognitive impairment may be treatable, with treatment not offered owing to the perception of ultimate futility or expense, or both. One of the causes of terminal loss of consciousness or decreased lucidity can be inadequate cerebral oxygen delivery. We report five cases from four institutions where an infusion of a hemoglobin-based oxygen carrier to patients who were unconscious or not lucid owing to acute severe anemia (hemoglobin range, 2.1-5.2 g/dL) resulted in awakening or lucidity. We review briefly human cognitive function and anemia and remark about the use of a hemoglobin-based oxygen carrier for acute severe anemia when red cell transfusion is not an option.

Cerebrovascular Accident in a 65-Year-Old Patient with Rothia dentocariosa-Associated Endocarditis.

A 65-year-old male patient with a history of heart valve replacement surgery after aortic valve stenosis and a family history of heart disease presented to the emergency room with complaints of headache, fever, back pain, and general malaise. Multiple blood samples during the patient's hospitalization cultured showed Rothia dentocariosa. The patient was started on daily intravenous ceftriaxone and vancomycin. In the following weeks, the patient's condition deteriorated with additional symptoms, persistent inflammatory markers, and elevated fever consistent with R. dentocariosa infection. The patient's clinical progression led to a cerebrovascular accident that was resolved with thrombectomy. Full symptomatic relief occurred after a valve replacement. R. dentocariosa, a common mouth flora, is not commonly pathogenic. This case is of particular importance as severe complications involving this bacterium are rare. There is an extreme paucity of cases involving deadly complications of R. dentocariosa, and there is no general consensus involving standard treatment regimen for this bacterium. We believe that this paper adds to clinical knowledge surrounding R. dentocariosa.

Artificial intelligence and COVID-19: A multidisciplinary approach.

The COVID-19 pandemic is taking a colossal toll in human suffering and lives. A significant amount of new scientific research and data sharing is underway due to the pandemic which is still rapidly spreading. There is now a growing amount of coronavirus related datasets as well as published papers that must be leveraged along with artificial intelligence (AI) to fight this pandemic by driving news approaches to drug discovery, vaccine development, and public awareness. AI can be used to mine this avalanche of new data and papers to extract new insights by cross-referencing papers and searching for patterns that AI algorithms could help discover new possible treatments or help in vaccine development. Drug discovery is not a trivial task and AI technologies like deep learning can help accelerate this process by helping predict which existing drugs, or brand-new drug-like molecules could treat COVID-19. AI techniques can also help disseminate vital information across the globe and reduce the spread of false information about COVID-19. The positive power and potential of AI must be harnessed in the fight to slow the spread of COVID-19 in order to save lives and limit the economic havoc due to this horrific disease.

Desmopressin-Induced Severe Hyponatremia with Central Pontine Myelinolysis: A Case Report.

Desmopressin, a synthetic vasopressin analog, is used to treat central diabetes insipidus, hemostatic disorders such as von Willebrand's disease, and nocturnal enuresis. We present the case of a 69-year-old man who developed severe hyponatremia during treatment with intranasal desmopressin at 10 µg twice daily for chronic polyuria and nocturia thought to be due to central diabetes insipidus. After 5 months of therapy, the patient noticed progressive fatigue, anorexia, dizziness, weakness, light-headedness, decreased concentration, and new-onset falls. At 6 months of therapy, the patient was brought to the emergency department for altered mental status and was found to be severely hyponatremic with a serum sodium level of 96 mmol/L, down from a value of 134 mmol/L at the initiation of therapy. The intranasal desmopressin was discontinued and the patient was admitted to the intensive care unit where the hyponatremia was slowly corrected over the next week to 132 mmol/L, never increasing by more than 8 mmol/L a day, with careful fluid management. This included infusion of over 11 L of 5% dextrose to account for a high urine output, which peaked at 7.4 L in 1 day. However, while the recommended rate for sodium correction was followed, the patient's magnetic resonance imaging of the brain obtained after discharge displayed evidence of central pontine myelinolysis. Despite this finding, the patient eventually returned to his baseline mental status with no permanent neurologic deficits.