Repetitive transcranial magnetic stimulation modulates brain connectivity in children with self-limited epilepsy with centrotemporal spikes.

Objective: Self-limited epilepsy with centrotemporal spikes (SeLECTS) is a common pediatric syndrome in which interictal epileptiform discharges (IEDs) emerge from the motor cortex and children often develop language deficits. IEDs may induce these language deficits by pathologically enhancing brain connectivity. Using a sham-controlled design, we test the impact of inhibitory low-frequency repetitive transcranial magnetic stimulation (rTMS) on connectivity and IEDs in SeLECTS.

Second-order group knockoffs with applications to genome-wide association studies.

Motivation: Conditional testing via the knockoff framework allows one to identify-among a large number of possible explanatory variables-those that carry unique information about an outcome of interest and also provides a false discovery rate guarantee on the selection. This approach is particularly well suited to the analysis of genome-wide association studies (GWAS), which have the goal of identifying genetic variants that influence traits of medical relevance.

Results: While conditional testing can be both more powerful and precise than traditional GWAS analysis methods, its vanilla implementation encounters a difficulty common to all multivariate analysis methods: it is challenging to distinguish among multiple, highly correlated regressors.

Repetitive Transcranial Magnetic Stimulation Modulates Brain Connectivity in Children with Self-limited Epilepsy with Centrotemporal Spikes.

Objective: Interictal epileptiform discharges (IEDs) alter brain connectivity in children with epilepsy; this connectivity change may be a mechanism by which epilepsy induces cognitive deficits. Here, we test whether repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique, modulates connectivity and reduces IEDs in children with epilepsy.

Methods: Nineteen children with self-limited epilepsy with centrotemporal spikes (SeLECTS) participated in a cross-over study comparing the impact of active vs.

Age-associated proteins explain the role of medial temporal lobe networks in Alzheimer's disease.

The structural connectivity (SC) of the medial temporal lobe and its associated cortical anterior temporal and posterior medial networks (MTL-AT-PM) is linked to pathologies and memory decline in Alzheimer's disease (AD). However, neuroimaging analyses cannot tell us how SC changes occur in AD at the molecular level and do not provide a means of intervening to slow/prevent pathology-related changes in MTL-AT-PM SC. The current study aimed to understand how and where AD-related changes occur within MTL-AT-PM using proteomics.

Temporal tau asymmetry spectrum influences divergent behavior and language patterns in Alzheimer's disease.

Understanding the psychiatric symptoms of Alzheimer s disease (AD) is crucial for advancing precision medicine and therapeutic strategies. The relationship between AD behavioral symptoms and asymmetry in spatial tau PET patterns is not well-known. Braak tau progression implicates the temporal lobes early.

Stability of transcranial magnetic stimulation electroencephalogram evoked potentials in pediatric epilepsy.

Transcranial magnetic stimulation paired with electroencephalography (TMS-EEG) can measure local excitability and functional connectivity. To address trial-to-trial variability, responses to multiple TMS pulses are recorded to obtain an average TMS evoked potential (TEP). Balancing adequate data acquisition to establish stable TEPs with feasible experimental duration is critical when applying TMS-EEG to clinical populations.

Long-term persistence to onabotulinumtoxinA to prevent chronic migraine: results from 11 years of patient data from a tertiary headache center.

Objective: To determine if patients with chronic migraine continue onabotulinumtoxinA (onabotA) long-term.

Methods: We performed a retrospective cohort analysis using aggregated, de-identified patient data from the Stanford Headache Center. We included patients in California who received at least one prescription for onabotA during the years of 2011-2021.

Second-order group knockoffs with applications to GWAS.

Conditional testing via the knockoff framework allows one to identify -- among large number of possible explanatory variables -- those that carry unique information about an outcome of interest, and also provides a false discovery rate guarantee on the selection. This approach is particularly well suited to the analysis of genome wide association studies (GWAS), which have the goal of identifying genetic variants which influence traits of medical relevance. While conditional testing can be both more powerful and precise than traditional GWAS analysis methods, its vanilla implementation encounters a difficulty common to all multivariate analysis methods: it is challenging to distinguish among multiple, highly correlated regressors.

Beyond guilty by association at scale: searching for causal variants on the basis of genome-wide summary statistics.

Understanding the causal genetic architecture of complex phenotypes will fuel future research into disease mechanisms and potential therapies. Here, we illustrate the power of a novel framework: it detects, starting from summary statistics, and across the entire genome, sets of variants that carry non-redundant information on the phenotypes and are therefore more likely to be causal in a biological sense. The approach, implemented in open-source software, is also computationally efficient, requiring less than 15 minutes on a single CPU to perform genome-wide analysis.

Controlled Variable Selection from Summary Statistics Only? A Solution via GhostKnockoffs and Penalized Regression.

Identifying which variables do influence a response while controlling false positives pervades statistics and data science. In this paper, we consider a scenario in which we only have access to summary statistics, such as the values of marginal empirical correlations between each dependent variable of potential interest and the response. This situation may arise due to privacy concerns, e.

Impaired 24-h activity patterns are associated with an increased risk of Alzheimer's disease, Parkinson's disease, and cognitive decline.

Background: Sleep-wake regulating circuits are affected during prodromal stages in the pathological progression of both Alzheimer's disease (AD) and Parkinson's disease (PD), and this disturbance can be measured passively using wearable devices. Our objective was to determine whether accelerometer-based measures of 24-h activity are associated with subsequent development of AD, PD, and cognitive decline.

Methods: This study obtained UK Biobank data from 82,829 individuals with wrist-worn accelerometer data aged 40 to 79 years with a mean (± SD) follow-up of 6.

Assessing the Assisted Six-Minute Cycling Test as a Measure of Endurance in Non-Ambulatory Patients with Spinal Muscular Atrophy (SMA).

Assessing endurance in non-ambulatory individuals with Spinal Muscular Atrophy (SMA) has been challenging due to limited evaluation tools. The Assisted 6-Minute Cycling Test (A6MCT) is an upper limb ergometer assessment used in other neurologic disorders to measure endurance. To study the performance of the A6MCT in the non-ambulatory SMA population, prospective data was collected on 38 individuals with SMA (13 sitters; 25 non-sitters), aged 5 to 74 years (mean = 30.

Organ aging signatures in the plasma proteome track health and disease.

Animal studies show aging varies between individuals as well as between organs within an individual, but whether this is true in humans and its effect on age-related diseases is unknown. We utilized levels of human blood plasma proteins originating from specific organs to measure organ-specific aging differences in living individuals. Using machine learning models, we analysed aging in 11 major organs and estimated organ age reproducibly in five independent cohorts encompassing 5,676 adults across the human lifespan.

Major Adverse Dystrophinopathy Events (MADE) Score as Marker of Cumulative Morbidity and Risk for Mortality in Boys with Duchenne Muscular Dystrophy.

Background: Overlapping symptoms from cardiomyopathy, respiratory insufficiency, and skeletal myopathy confound assessment of heart failure in Duchenne Muscular Dystrophy. We developed an ordinal scale of multiorgan clinical variables that reflect cumulative disease burden-the ajor dverse ystrophinopathy vent ) Score. We hypothesized that a higher MADE score would be associated with increased mortality in boys with Duchenne Muscular Dystrophy.

The introduction of the CGRP monoclonal antibodies and their effect on the prescription patterns of chronic migraine preventive medications in a tertiary headache center: A retrospective, observational analysis.

Objective: To determine the effect of the introduction of the calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) in 2018 on the prescribing of older medications for the prevention of chronic migraine.

Background: Prior to 2018, the preventive treatment of migraine borrowed from medications intended to treat other illnesses with the last medication, onabotulinumtoxinA, receiving Food and Drug Administration (FDA) approval for the prevention of chronic migraine in 2010. The FDA approval of three CGRP mAbs in 2018 provided the ideal natural experiment to assess how the introduction of these medications, and a fourth in 2020, affected the generally stable migraine preventive medications market.

Loop diuretics association with Alzheimer's disease risk.

To investigate whether exposure history to two common loop diuretics, bumetanide and furosemide, affects the risk of developing Alzheimer's disease (AD) after accounting for socioeconomic status and congestive heart failure. Individuals exposed to bumetanide or furosemide were identified in the Stanford University electronic health record using the de-identified Observational Medical Outcomes Partnership platform. We matched the AD case cohort to a control cohort (1:20 case:control) on gender, race, ethnicity, and hypertension, and controlled for variables that could potentially be collinear with bumetanide exposure and/or AD diagnosis.

Improving genetic risk prediction across diverse population by disentangling ancestry representations.

Risk prediction models using genetic data have seen increasing traction in genomics. However, most of the polygenic risk models were developed using data from participants with similar (mostly European) ancestry. This can lead to biases in the risk predictors resulting in poor generalization when applied to minority populations and admixed individuals such as African Americans.

Bumetanide Exposure Association with Alzheimer's Disease Risk.

Background: To investigate whether exposure history to two common loop diuretics affects the risk of developing Alzheimer's disease (AD) after accounting for socioeconomic status and congestive heart failure.

Methods: Individuals exposed to bumetanide or furosemide were identified in the Stanford University electronic health record using the deidentified Observational Medical Outcomes Partnership platform. We matched the AD case cohort to a control cohort (1:20 case:control) on gender, race, ethnicity, hypertension and controlled for variables that could potentially be collinear with bumetanide exposure and/or AD diagnosis.