Publications by authors named "Michael Breen"

Eating disorders (ED) and obsessive-compulsive disorder (OCD) exhibit significant clinical and genetic overlap, yet their shared molecular mechanisms remain unclear. We conducted a transcriptomic investigation of the dorsolateral prefrontal cortex (DLPFC) and caudate from 86 controls, 57 ED, and 27 OCD cases. ED was associated with robust differentially expressed genes (DEGs): 102 DEGs the DLPFC and 222 in the caudate (FDR < 1%) and replicated in an independent cohort.

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Adenosine deaminases acting on RNA (ADARs) impact diverse cellular processes and pathological conditions, but their functions in early cell-fate specification remain less understood. To gain insights here, we began by charting time-course RNA editing profiles in human organs from fetal to adult stages. Next, we utilized hPSC differentiation to experimentally probe ADARs, harnessing brain organoids as neural specific, and teratomas as pan-tissue developmental models.

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Article Synopsis
  • A study investigated the impact of Maternal Immune Activation (MIA) on child neurodevelopment using neuroimaging data from a large cohort of mother-child pairs from the Generation R Study.
  • Researchers examined levels of specific cytokines during pregnancy and employed various neuroimaging techniques to analyze brain development in children at ages 10 and 14.
  • The results showed no significant association between MIA and any neuroimaging outcomes, contradicting earlier findings that indicated brain abnormalities in neonates exposed to MIA.
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Objective: Globally, obstetric fistula is a tragic outcome following obstructed labour. Failure of complex repair and post-operative incontinence are common. We describe an innovative surgical technique incorporating the rectus abdominus flap at the time of fistula repair.

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Activity-dependent neuroprotective protein (ADNP) syndrome is a rare neurodevelopmental disorder resulting in intellectual disability, developmental delay and autism spectrum disorder (ASD) and is due to mutations in the ADNP gene. Ketamine treatment has emerged as a promising therapeutic option for ADNP syndrome, showing safety and apparent behavioral improvements in a first open label study. However, the molecular perturbations induced by ketamine remain poorly understood.

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Adaptations of the immune system throughout gestation have been proposed as important mechanisms regulating successful pregnancy. Dysregulation of the maternal immune system has been associated with adverse maternal and fetal outcomes. To translate findings from mechanistic preclinical studies to human pregnancies, studies of serum immune markers are the mainstay.

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Adenosine-to-inosine (A-to-I) editing is a prevalent post-transcriptional RNA modification within the brain. Yet, most research has relied on postmortem samples, assuming it is an accurate representation of RNA biology in the living brain. We challenge this assumption by comparing A-to-I editing between postmortem and living prefrontal cortical tissues.

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The prefrontal cortex (PFC) is a region of the brain that in humans is involved in the production of higher-order functions such as cognition, emotion, perception, and behavior. Neurotransmission in the PFC produces higher-order functions by integrating information from other areas of the brain. At the foundation of neurotransmission, and by extension at the foundation of higher-order brain functions, are an untold number of coordinated molecular processes involving the DNA sequence variants in the genome, RNA transcripts in the transcriptome, and proteins in the proteome.

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Article Synopsis
  • - The study investigates differences in adenosine-to-inosine (A-to-I) RNA editing levels between postmortem and living prefrontal cortex tissues, revealing over 70,000 sites with higher editing in postmortem samples.
  • - Increased editing in postmortem tissues is associated with inflammation, hypoxia, and higher expression levels, particularly in non-neuronal cells, suggesting that such editing may reflect postmortem changes rather than accurate living brain activity.
  • - The research highlights that higher A-to-I editing in living tissues corresponds to evolutionarily conserved and developmentally relevant sites, indicating the complex regulatory roles of RNA editing in brain function and potential implications for neurological disorders.
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Recovery from respiratory pneumococcal infections generates lung-localized protection against heterotypic bacteria, mediated by resident memory lymphocytes. Optimal protection in mice requires re-exposure to pneumococcus within days of initial infection. Serial surface marker phenotyping of B cell populations in a model of pneumococcal heterotypic immunity revealed that bacterial re-exposure stimulates the immediate accumulation of dynamic and heterogeneous populations of B cells in the lung, and is essential for the establishment of lung resident memory B (B) cells.

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Article Synopsis
  • Obsessive-compulsive disorder (OCD) affects about 1% of people and has a strong genetic component, but previous studies have not fully explained its genetic causes or biological mechanisms.
  • A large genome-wide association study (GWAS) analyzed data from over 53,000 OCD cases and over 2 million control participants, identifying 30 significant genetic markers related to OCD and suggesting a 6.7% heritability from SNPs.
  • The research also found 249 candidate risk genes linked to OCD, particularly in specific brain regions, and showed genetic correlations with various psychiatric disorders, laying the groundwork for further studies and potential treatments.
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Study Objective: Fellowship program directors (FPDs) play an important role in the development of fellows and learners, but little is known about their demographics. This cross-sectional study aims to examine the characteristics of minimally invasive gynecologic surgery (MIGS) FPDs.

Design: A retrospective cross-sectional study.

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Activity-dependent neuroprotective protein (ADNP) syndrome is a rare neurodevelopmental disorder resulting in intellectual disability, developmental delay and autism spectrum disorder (ASD) and is due to mutations in the gene. Ketamine treatment has emerged as a promising therapeutic option for ADNP syndrome, showing safety and apparent behavioral improvements in a first open label study. However, the molecular perturbations induced by ketamine remain poorly understood.

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Applications of machine learning in the biomedical sciences are growing rapidly. This growth has been spurred by diverse cross-institutional and interdisciplinary collaborations, public availability of large datasets, an increase in the accessibility of analytic routines, and the availability of powerful computing resources. With this increased access and exposure to machine learning comes a responsibility for education and a deeper understanding of its bases and bounds, borne equally by data scientists seeking to ply their analytic wares in medical research and by biomedical scientists seeking to harness such methods to glean knowledge from data.

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COVID-19 highlighted interconnections between matters of identity and citizenship, vulnerability, and inclusion in/exclusion from systems of care in times of crisis. Migrant workers from Nagaland state, northeast India, were disproportionately impacted by the pandemic's socioeconomic consequences. The public health emergency brought into question who is 'Indian' and the citizenship rights attached to that identity, heightening migrants' exclusion from central structures.

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Background: The pathophysiology of autism spectrum disorder (ASD) involves genetic and environmental factors. Mounting evidence demonstrates a role for the gut microbiome in ASD, with signaling via short-chain fatty acids (SCFA) as one mechanism. Here, we utilize mice carrying deletion to exons 4-22 of Shank3 (Shank3) to model gene by microbiome interactions in ASD.

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Streptococcus pneumoniae is the most common etiology of bacterial pneumonia, one of the leading causes of death in children and the elderly worldwide. During non-lethal infections with S. pneumoniae, lymphocytes accumulate in the lungs and protect against reinfection with serotype-mismatched strains.

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Rock climbing has evolved from a method for alpine mountaineering into a popular recreational activity and competitive sport. Advances in safety equipment and the rapid growth of indoor climbing facilities has enabled climbers to focus on the physical and technical movements needed to elevate performance. Through improved training methods, climbers can now achieve ascents of extreme difficulty.

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Stock assessments routinely evaluate the status of commercially harvested species, but seldom account for the possible mortality of released or escaping fish. This study presents a method for estimating the escape survival of the red mullet () from demersal trawling in the Central Mediterranean Sea. Fish escaping from the trawl codend were collected in a detachable cage, which was lined to reduce water flow and protect the sampled fish from further fatigue and injury.

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Autistic adults possess many skills sought by employers, but may be at a disadvantage in the workplace if social-communication differences negatively impact teamwork. We present a novel collaborative virtual reality (VR)-based activities simulator, called ViRCAS, that allows autistic and neurotypical adults to work together in a shared virtual space, offering the chance to practice teamwork and assess progress. ViRCAS has three main contributions: 1) a new collaborative teamwork skills practice platform; 2) a stakeholder-driven collaborative task set with embedded collaboration strategies; and 3) a framework for multimodal data analysis to assess skills.

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Autistic individuals face difficulties in finding and maintaining employment, and studies have shown that the job interview is often a significant barrier to obtaining employment. Prior computer-based job interview training interventions for autistic individuals have been associated with better interview outcomes. These previous interventions, however, do not leverage the use of multimodal data that could give insight into the emotional underpinnings of autistic individuals' challenges in job interviews.

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Article Synopsis
  • * A study involving 133 women with CPP showed that while somatoform dissociation did not relate to pain severity or surgical history, it did affect health-related quality of life, specifically physical and mental health outcomes.
  • * The research suggests focusing on individual symptoms of somatoform dissociation could improve quality of life for trauma-exposed women with CPP, and highlights the need for further studies and trauma-informed care in clinical settings.
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