Objective: This study aimed to investigate whether transcutaneous vagus nerve stimulation (tVNS) at different frequencies affects phase-amplitude coupling among regions of the brain linked to mood and memory disorders using simultaneous magnetoencephalography (MEG) in healthy participants.
Materials And Methods: Phase-amplitude coupling was measured among brain areas in response to different stimulation frequencies of tVNS using concurrent MEG and tVNS in 17 healthy participants. The 4 protocols were: 24 Hz cymba concha, 1 Hz cymba concha, PFM cymba concha, and 24 Hz ear lobe.
Exon skipping technologies enable exclusion of targeted exons from mature mRNA transcripts, which have broad applications in medicine and biotechnology. Existing techniques including antisense oligonucleotides, targetable nucleases, and base editors, while effective for specific applications, remain hindered by transient effects, genotoxicity, and inconsistent exon skipping. To overcome these limitations, here we develop SPLICER, a toolbox of next-generation base editors containing near-PAMless Cas9 nickase variants fused to adenosine or cytosine deaminases for the simultaneous editing of splice acceptor (SA) and splice donor (SD) sequences.
View Article and Find Full Text PDFBackground: To build research capacity for early-career faculty conducting HIV/STI research with minoritized communities and to enhance diversity in the scientific workforce, the University of California, San Francisco (UCSF) Center for AIDS Prevention (CAPS) conducts a training program for visiting professors (VPs), begun in 1996. VPs are in residence at CAPS for three summers, complete a pilot research project, and prepare National Institutes of Health (NIH) grant proposals. Best practices and key elements for successfully training scholars of color, and others who work with minoritized communities, are identified.
View Article and Find Full Text PDFJ Psychopathol Clin Sci
February 2025
Psychological functioning is shaped by how people navigate their environment. Accordingly, psychopathology is often caused and maintained by patterns of responding to the environment that do not meet situational demands. In particular, psychopathology is often expressed in an inflexible or intense manner of coping with stressful situations.
View Article and Find Full Text PDFHuntington's disease (HD) is an inherited and ultimately fatal neurodegenerative disorder caused by an expanded polyglutamine-encoding CAG repeat within exon 1 of the huntingtin (HTT) gene, which produces a mutant protein that destroys striatal and cortical neurons. Importantly, a critical event in the pathogenesis of HD is the proteolytic cleavage of the mutant HTT protein by caspase-6, which generates fragments of the N-terminal domain of the protein that form highly toxic aggregates. Given the role that proteolysis of the mutant HTT protein plays in HD, strategies for preventing this process hold potential for treating the disorder.
View Article and Find Full Text PDFThe alternative model of personality disorders (AMPD) traits were designed to maintain continuity with the Section II personality disorder (PD) diagnoses by retaining the same clinical information. Whether the AMPD traits achieve this is not well established. Prior work testing incremental validity of AMPD traits and Section II diagnoses is limited by the fact each model was measured by a different instrument or rater, making it unclear whether discrepancies are due to the constructs or methods.
View Article and Find Full Text PDFBest practices in cardiac arrest depend on continuous high-quality chest compressions, appropriate ventilatory management, early defibrillation of shockable rhythms, and identification and treatment of reversible causes. Although most patients can be treated according to highly vetted treatment guidelines, some special situations in cardiac arrest arise where additional skills and preparation can improve outcomes. Situations covered in this section involve cardiac arrest in context of electrical injuries, asthma, allergic reactions, pregnancy, trauma, electrolyte imbalances, toxic exposures, hypothermia, drowning, pulmonary embolism, and left ventricular assist devices.
View Article and Find Full Text PDFPurpose: Individuals diagnosed with cancer between 15 and 39 years (adolescent and young adult [AYA]) face unique vulnerability. Detail is lacking about care delivery for these patients, especially those with ALL. We address these knowledge gaps by describing AYA ALL care delivery details at National Cancer Institute Community Oncology Research Program (NCORP) (sub)affiliates by model of care.
View Article and Find Full Text PDFAnnu Int Conf IEEE Eng Med Biol Soc
July 2023
Transcutaneous vagus nerve stimulation (tVNS) is a non-invasive method of brain stimulation that has been investigated for its use in the clinical treatment of a number of different conditions. There has been little investigation into the stimulation current that is delivered and the effect on individual variability in response to tVNS.Seventeen participants underwent tVNS, and stimulation current was determined based on individual pain threshold.
View Article and Find Full Text PDFAnnu Int Conf IEEE Eng Med Biol Soc
July 2023
This study characterizes the neurophysiological mechanisms underlying electromagnetic imaging signals using stability analysis. Researchers have proposed that transitions between conscious awake and anaesthetised states, and other brain states more generally, may result from system stability changes. The concept of stability in dynamical systems theory provides a mathematical framework to describe this possibility.
View Article and Find Full Text PDFSeveral polymorphisms altering the activity have already been identified. The geographical distribution of variants has been extensively studied and has been demonstrated to vary significantly among different ethnic population. Here, we describe the genetic variability of human N-acetyltransferase 2 () gene and the predominant genotype-deduced acetylation profiles of Brazilians.
View Article and Find Full Text PDFMachine learning can be used to define subtypes of psychiatric conditions based on shared clinical and biological foundations, presenting a crucial step toward establishing biologically based subtypes of mental disorders. With the goal of identifying subtypes of disease progression in schizophrenia, here we analyzed cross-sectional brain structural magnetic resonance imaging (MRI) data from 4,291 individuals with schizophrenia (1,709 females, age=32.5 years±11.
View Article and Find Full Text PDFBackground: Complex regional pain syndrome type 1 (CRPS-1) is a rare, disabling and sometimes chronic disorder usually arising after a trauma. This exploratory study examined whether patients with chronic CRPS-1 have a different genetic profile compared with those who do not have the condition.
Methods: Exome sequencing was performed to seek altered non-synonymous SNP allele frequencies in a discovery cohort of well-characterised patients with chronic CRPS-1 (n34) compared with population databases.
Mol Ther Nucleic Acids
September 2023
Duchenne muscular dystrophy is an X-linked monogenic disease caused by mutations in the dystrophin gene () characterized by progressive muscle weakness, leading to loss of ambulation and decreased life expectancy. Since the current standard of care for Duchenne muscular dystrophy is to merely treat symptoms, there is a dire need for treatment modalities that can correct the underlying genetic mutations. While several gene replacement therapies are being explored in clinical trials, one emerging approach that can directly correct mutations in genomic DNA is base editing.
View Article and Find Full Text PDFIEEE Trans Neural Syst Rehabil Eng
September 2023
Altered brain functional connectivity has been observed in conditions such as schizophrenia, dementia and depression and may represent a target for treatment. Transcutaneous vagus nerve stimulation (tVNS) is a form of non-invasive brain stimulation that is increasingly used in the treatment of a variety of health conditions. We previously combined tVNS with magnetoencephalography (MEG) and observed that various stimulation frequencies affected different brain areas in healthy individuals.
View Article and Find Full Text PDFPrime editing (PE) is a highly versatile CRISPR-Cas9 genome editing technique. The current constructs, however, have variable efficiency and may require laborious experimental optimization. This study presents statistical models for learning the salient epigenomic and sequence features of target sites modulating the editing efficiency and provides guidelines for designing optimal PEs.
View Article and Find Full Text PDFDespite many initiatives taken by funding bodies and health care organisations, the 10/90 gap in health care and health system research between low and middle-income countries (LIMC) and high income countries is still widely recognised. We aimed to quantify the contribution of LMIC in high impact medical journals and compare the results with the previous survey conducted in 2000. Research articles were anaylsed to determine the origin of data and authorship affiliated countries in a calendar year (2017) for five journals: British Medical Journal, The Lancet, New England Journal of Medicine (NEJM), Annals of Internal Medicine and the Journal of the American Medical Association.
View Article and Find Full Text PDFBest practices in cardiac arrest depend on continuous high-quality chest compressions, appropriate ventilatory management, early defibrillation of shockable rhythms, and identification and treatment of reversible causes. Although most patients can be treated according to highly vetted treatment guidelines, some special situations in cardiac arrest arise where additional skills and preparation can improve outcomes. Situations covered in this section involve cardiac arrest in context of electrical injuries, asthma, allergic reactions, pregnancy, trauma, electrolyte imbalances, toxic exposures, hypothermia, drowning, pulmonary embolism, and left ventricular assist devices.
View Article and Find Full Text PDFPrime editor (PE) is a highly versatile CRISPR-Cas9 genome editing technique. The current constructs, however, have variable efficiency and may require laborious experimental optimization. This study presents statistical models for learning the salient epigenomic and sequence features of target sites modulating the editing efficiency and provides guidelines for designing optimal PEs.
View Article and Find Full Text PDFRecent work presented a framework for space-time-resolved neurophysiological process imaging that augments existing electromagnetic source imaging techniques. In particular, a nonlinear Analytic Kalman filter (AKF) has been developed to efficiently infer the states and parameters of neural mass models believed to underlie the generation of electromagnetic source currents. Unfortunately, as the initialization determines the performance of the Kalman filter, and the ground truth is typically unavailable for initialization, this framework might produce suboptimal results unless significant effort is spent on tuning the initialization.
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