Publications by authors named "Daniel O'Connor"

Purpose: Accelerating MR acquisition is essential for image guided therapeutic applications. Compressed sensing (CS) has been developed to minimize image artifacts in accelerated scans, but the required iterative reconstruction is computationally complex and difficult to generalize. Convolutional neural networks (CNNs)/Transformers-based deep learning (DL) methods emerged as a faster alternative but face challenges in modeling continuous k-space, a problem amplified with non-Cartesian sampling commonly used in accelerated acquisition.

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Objective: Optogenetics is a valuable and widely-used technique that allows precise perturbations of selected groups of cells with high temporal and spatial resolution by using optical systems and genetic engineering technologies. This study aims to develop Opto-Myomatrix, a novel optogenetic tool for precise muscle fiber control and high-resolution electrophysiological recording.

Method: Based on a flexible and biocompatible polymer substrate, the device incorporates an integrated μLED that delivers light at 465 nm for optogenetic stimulation and 32 PEDOT:PSS-coated electrodes for electromyography (EMG) recording.

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Salmonella Typhi (S. Typhi), the causative agent of typhoid disease, remains a major public health concern. Owing to the human-restricted nature of S.

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Mice rely heavily on their sophisticated whisker somatosensory system to explore and navigate their surroundings. The primary whisker somatosensory cortex (wS1) receives contralateral sensory input due to a complete crossover of axonal projections ascending from the brainstem to the thalamus, resulting in a somatotopic map that exclusively represents the contralateral side of the face. This axonal crossover is disrupted in mice with a conditional knockout of the Robo3 gene, leading to abnormal bilateral representations of the whiskers in wS1.

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Ebola virus disease (EVD) outbreaks are increasing, posing significant threats to affected communities. Effective outbreak management depends on protecting frontline health workers, a key focus of EVD vaccination strategies. IgG specific to the viral glycoprotein serves as the correlate of protection for recent vaccine licensures.

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A hallmark of complex goal-directed movement sequences is the ability to rapidly switch motor programs by integrating incoming sensations with action context , yet the underlying neural implementation remains elusive. Here, we demonstrate a network mechanism for flexibly adjusting the sensitivity of ongoing motor execution to external inputs in different sensorimotor contexts. We trained mice to make sequences of licks directed at a moving target.

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The field of individualized, or N-of-1, therapy development is growing and increasingly gaining attention as a novel option for people with serious diseases, caused by unique genetic variants for whom approved therapies are not available. The N-of-1 taskforce of the International Rare Disease Research Consortium previously outlined a roadmap of aspects involved in N-of-1 therapy development and implementation. Here, this follow-up paper looks forward and reflects on how to address existing gaps to advance the current state of individualized interventions toward an integrated and sustainable treatment development model.

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Blanching is the process of removing the testa or seed coat (skin) from peanuts, and a genotype's capacity to release its testa is referred to as its blanchability. The genotype, seed quality, harvest date, level of maturity, as well as the length of time and temperature of the post-harvest storage period, all influence peanut's blanchability. This characteristic holds significant value in the production of food items made from peanuts.

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Purpose The characterization of opioid usage in revision total knee arthroplasty (rTKA) remains incomplete. This study aimed to evaluate postoperative opioid consumption, measured in morphine milligram equivalents (MME), as well as hospital length of stay and discharge destinations such as home versus skilled nursing facility following revision TKA. Methods Patients who underwent rTKA between 2010 and 2018 were assessed for preoperative opioid use and monitored for 24 months postoperatively.

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Objectives: Sepsis is a life-threatening medical emergency, with a profound healthcare burden globally. Its pathophysiology is complex, heterogeneous and temporally dynamic, making diagnosis challenging. Medical management is predicated on early diagnosis and timely intervention.

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Perception, a cognitive construct, emerges through sensorimotor integration (SMI). The genetic mechanisms that shape SMI required for perception are unknown. Here, we demonstrate in mice that expression of the autism/intellectual disability gene, Syngap1, in cortical excitatory neurons is required for the formation of somatomotor networks that promote SMI-mediated perception.

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Somatosensory cortex activity relates both to sensation and movement, reflecting their intimate relationship, but the extent and nature of sensory-motor interactions in the somatosensory cortex remain unclear. Here, we investigated perception-related sensory and motor signals in the whisker areas of mouse primary (wS1) and secondary (wS2) somatosensory cortices. We recorded neuronal activity while mice performed a whisker detection task using two alternative lickports, one each to indicate the presence or absence of a whisker deflection on a given trial.

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In recent years, a small number of people with rare diseases caused by unique genetic variants have been treated with therapies developed specifically for them. This pioneering field of genetic N-of-1 therapies is evolving rapidly, giving hope for the individualized treatment of people living with very rare diseases. In this Review, we outline the concept of N-of-1 individualized therapies, focusing on genetic therapies, and illustrate advances and challenges in the field using cases for which therapies have been successfully developed.

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Article Synopsis
  • Early phase clinical trials focus on evaluating the safety and tolerability of new therapies, primarily using investigator and lab results rather than patient feedback.
  • A recent expert roundtable brought together 22 stakeholders to discuss the need for a universal patient-reported outcomes (PRO) model in early phase trials and how to effectively incorporate PROs to assess tolerability and guide treatment decisions.
  • The discussions yielded key recommendations and identified priority areas for further research on integrating patient feedback into early trials to improve safety and symptom management.
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Sensory feedback is essential for motor performance and must adapt to task demands. Muscle spindle afferents (MSAs) are a major primary source of feedback about movement, and their responses are readily modulated online by gain-controller fusimotor neurons and other mechanisms. They are therefore a powerful site for implementing flexible sensorimotor control.

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The neural basis of tongue mechanosensation remains largely mysterious despite the tongue's high tactile acuity, sensitivity, and relevance to ethologically important functions. We studied terminal morphologies and tactile responses of lingual afferents from the trigeminal ganglion. Fungiform papillae, the taste-bud-holding structures in the tongue, were convergently innervated by multiple Piezo2 trigeminal afferents, whereas single trigeminal afferents branched into multiple adjacent filiform papillae.

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  • Metastatic castration-resistant prostate cancer (mCRPC) is a severe illness that often fails standard treatments, presenting a serious challenge for patient survival.
  • ARX517 is a promising new antibody-drug conjugate that targets the prostate-specific membrane antigen (PSMA) with a design that allows for direct delivery of a cytotoxic agent to tumor cells while minimizing premature release.
  • Preclinical studies in various prostate cancer models show that ARX517 effectively inhibits tumor growth and has a favorable safety profile, leading to its evaluation in a phase I clinical trial.
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  • Outbreaks of Ebolaviruses, like Sudanvirus in Uganda in 2022, highlight the need for vaccines that target more than just the Zaire ebolavirus, which is currently the only one in use.
  • A new vaccine regimen, Ad26.ZEBOV/MVA-BN-Filo, was developed and tested in the EBL2001 clinical trial, aiming to enhance immunity against various Ebolaviruses.
  • Researchers sequenced B cell receptors from trial participants and created a database of Ebolavirus-specific antibodies, revealing important patterns in immune responses and demonstrating the potential for computational techniques to analyze immune repertoires effectively.
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Complex movements involve highly coordinated control of local muscle elements. Highly controlled perturbations of motor outputs can reveal insights into the neural control of movements. Here we introduce an optogenetic method, compatible with electromyography (EMG) recordings, to perturb muscles in transgenic mice.

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  • Streptococcus pneumoniae colonization in the upper respiratory tract is significantly linked to the onset of pneumonia, particularly in vulnerable populations like young children and older adults.
  • Research revealed that older adults exhibit unique immunological responses to pneumococcal infection, with notable neutrophil activation and increased CXCL9 and CXCL10 levels, indicating a distinct gene expression pattern compared to younger adults.
  • Unlike younger adults, older adults did not show increased monocyte recruitment after infection, but those protected from colonization demonstrated enhanced T cell activity, suggesting that age-related immune changes may increase susceptibility to infection.
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