Mark A. Smith
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View article: The Pathway to Proof‐of‐Concept for BNC210, a Negative Allosteric Modulator of the Alpha‐7 Nicotinic Acetylcholine Receptor (nAChR), for Treatment of Psychiatric Disease
The Pathway to Proof‐of‐Concept for BNC210, a Negative Allosteric Modulator of the Alpha‐7 Nicotinic Acetylcholine Receptor (nAChR), for Treatment of Psychiatric Disease Open
BNC210 is an investigational small molecule selective negative allosteric modulator of the alpha‐7 nicotinic acetylcholine receptor (α7 nAChR). It is an anxiolytic compound with a novel mechanism of action. In a series of Phase 1 clinical …
View article: Trisomy 21 impairs synchronized activity and connectivity in developing human down syndrome cortical excitatory neuron networks
Trisomy 21 impairs synchronized activity and connectivity in developing human down syndrome cortical excitatory neuron networks Open
Summary Down syndrome (DS) is the most common genetic cause of intellectual disability, affecting one in 700 live births worldwide, and is caused by trisomy of the human chromosome 21 (Hsa21). Here, we investigated whether trisomy 21 alter…
View article: Role of Transporters and Enzymes in Metabolism and Distribution of 4-Chlorokynurenine (AV-101)
Role of Transporters and Enzymes in Metabolism and Distribution of 4-Chlorokynurenine (AV-101) Open
4-Chlorokynurenine (4-Cl-KYN, AV-101) is a prodrug of a NMDA receptor antagonist and is in clinical development for potential CNS indications. We sought to further understand the distribution and metabolism of 4-Cl-KYN, as this information…
View article: Effect of fasedienol (PH94B) pherine nasal spray and steroidal hormones on electrogram responses and autonomic nervous system activity in healthy adult volunteers
Effect of fasedienol (PH94B) pherine nasal spray and steroidal hormones on electrogram responses and autonomic nervous system activity in healthy adult volunteers Open
Objective Fasedienol (PH94B) is a pherine compound formulated as a nasal spray that is hypothesized to regulate olfactory‐amygdala circuits of fear and anxiety. Fasedienol's effect on the local electrogram of nasal chemosensory neurons (EG…
View article: Role of transporters and enzymes in metabolism and distribution of 4 chlorokynurenine and metabolites
Role of transporters and enzymes in metabolism and distribution of 4 chlorokynurenine and metabolites Open
4-chlorokynurenine (4-Cl-KYN) is in clinical development for potential CNS indications. We have sought to further understand the distribution and metabolism of 4-Cl-KYN as this information might provide a strategy to enhance the clinical d…
View article: Activity of osimertinib in a patient with stage IV non-small cell lung cancer harboring HER2 exon 19, p.L755P mutation: case report
Activity of osimertinib in a patient with stage IV non-small cell lung cancer harboring HER2 exon 19, p.L755P mutation: case report Open
This is the first report to our knowledge to demonstrate activity of osimertinib in a patient with NSCLC harboring HER2 exon 19, p.L755P mutation resulting in intra- and extracranial response. In the future, osimertinib could become a targ…
View article: Is there a consensus on peritonsillar abscess management?—an audit of a tertiary hospital in Australia
Is there a consensus on peritonsillar abscess management?—an audit of a tertiary hospital in Australia Open
Background: Peritonsillar abscess is the most common deep space infection of the head and neck. It can have life threatening complications if inadequately treated. The study aimed to analyse the workup and management trends of peritonsilla…
View article: CCDC 2218823: Experimental Crystal Structure Determination
CCDC 2218823: Experimental Crystal Structure Determination Open
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available …
View article: CCDC 2193041: Experimental Crystal Structure Determination
CCDC 2193041: Experimental Crystal Structure Determination Open
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available …
View article: CCDC 2193043: Experimental Crystal Structure Determination
CCDC 2193043: Experimental Crystal Structure Determination Open
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available …
View article: CCDC 2193042: Experimental Crystal Structure Determination
CCDC 2193042: Experimental Crystal Structure Determination Open
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available …
View article: CCDC 671179: Experimental Crystal Structure Determination
CCDC 671179: Experimental Crystal Structure Determination Open
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available …
View article: Diagnostic and management considerations in multicentric forms of laryngeal paraganglioma: a systematic review
Diagnostic and management considerations in multicentric forms of laryngeal paraganglioma: a systematic review Open
Background: Laryngeal paragangliomas (LPs) comprise a small subset of head and neck paragangliomas (HNPGLs), arising from the superior or inferior laryngeal paraganglia. Multicentric forms of LP are rare and should raise suspicion for here…
View article: Inclusive Education in Uganda - Examples of best practice
Inclusive Education in Uganda - Examples of best practice Open
There is a lack of research into what works in Inclusive Education (IE) in Uganda, as elsewhere in sub-Saharan Africa (SSA). Yet with children with disabilities (CwDs) constituting only 1.79% of total school enrolment, serious attention is…
View article: Decision Science for Machine Learning (DeSciML)
Decision Science for Machine Learning (DeSciML) Open
The increasing use of machine learning (ML) models to support high-consequence decision making drives a need to increase the rigor of ML-based decision making. Critical problems ranging from climate change to nonproliferation monitoring re…
View article: Discovery of 1<i>H-</i>Pyrazole Biaryl Sulfonamides as Novel G2019S-LRRK2 Kinase Inhibitors
Discovery of 1<i>H-</i>Pyrazole Biaryl Sulfonamides as Novel G2019S-LRRK2 Kinase Inhibitors Open
G2019S (GS) is the most prevalent mutation in the leucine rich repeat protein kinase 2 gene (LRRK2), a genetic predisposition that is common for Parkinson's disease, as well as for some forms of cancer, and is a shared risk allele for Croh…
View article: Discovery of G2019S-Selective Leucine Rich Repeat Protein Kinase 2 inhibitors with in vivo efficacy
Discovery of G2019S-Selective Leucine Rich Repeat Protein Kinase 2 inhibitors with in vivo efficacy Open
Mutations in the Leucine Rich Repeat Protein Kinase 2 gene (LRRK2) are the most common genetic causes of Parkinson's Disease (PD). The G2019S mutation is the most common inherited LRRK2 mutation, occurs in the kinase domain, and results in…
View article: Optimizing Machine Learning Decisions with Prediction Uncertainty.
Optimizing Machine Learning Decisions with Prediction Uncertainty. Open
these classifiers can be uncertain, rendering downstream decisions difficult. Herein, we provide a framework for: (1) quantifying and propagating uncertainty in ML classifiers; (2) formally linking ML outputs with the decision-making proce…
View article: Does mismatch negativity have utility for NMDA receptor drug development in depression?
Does mismatch negativity have utility for NMDA receptor drug development in depression? Open
Rapid antidepressant effects associated with ketamine have shifted the landscape for the development of therapeutics to treat major depressive disorder (MDD) from a monoaminergic to glutamatergic model. Treatment with ketamine, an N-methyl…
View article: A randomized cross-over trial to define neurophysiological correlates of AV-101 N-methyl-d-aspartate receptor blockade in healthy veterans
A randomized cross-over trial to define neurophysiological correlates of AV-101 N-methyl-d-aspartate receptor blockade in healthy veterans Open
The kynurenine pathway (KP) is a strategic metabolic system that combines regulation of neuronal excitability via glutamate receptor function and neuroinflammation via other KP metabolites. This pathway has great promise in treatment of de…
View article: A Randomized Trial of the N-Methyl-d-Aspartate Receptor Glycine Site Antagonist Prodrug 4-Chlorokynurenine in Treatment-Resistant Depression
A Randomized Trial of the N-Methyl-d-Aspartate Receptor Glycine Site Antagonist Prodrug 4-Chlorokynurenine in Treatment-Resistant Depression Open
Background Ketamine has rapid-acting antidepressant effects but is associated with psychotomimetic and other adverse effects. A 7-chlorokynurenic acid is a potent and specific glycine site N-methyl-d-aspartate receptor antagonist but cross…