Evaluation of DBS computational modeling methodologies using in-vivo electrophysiology in Parkinson's disease.

Deep brain stimulation (DBS) is an effective therapy for Parkinson's disease (PD) and other neuropsychiatric disorders, but its outcomes vary due to differences in patient selection, electrode placement, and programming. Optimizing DBS parameter settings requires postoperative adjustments through a trial-and-error process, which is complex and time-consuming. As such, researchers have been developing patient-specific computational models to help guide DBS programming.

Automated classification of seizure onset pattern using intracranial electroencephalogram signal of non-human primates.

To develop and validate a machine learning framework for the classification of distinct seizure onset patterns using intracranial EEG (iEEG) recordings in a non-human primate (NHP) model of penicillin-induced seizures.iEEG data were collected from six NHPs, comprising 1, 496 frontal and 549 temporal lobe seizures. Seizure onset patterns were manually categorized into five types: Sharp Activity (5-15 Hz), Low Amplitude Fast Activity (15-30 Hz), Delta Brush (1-3 Hz with bursts), High Amplitude Spike (2-5 Hz), and Polyspike.

Computational characterization of lymphocyte topology on whole slide images of glomerular diseases.

The complexity of distribution of inflammatory cells in the kidney is not well captured by conventional semiquantitative visual assessment. This study aims to computationally quantify the topology of lymphocytic inflammation and tested its clinical relevance. N=333 NEPTUNE/CureGN participants (N=155 focal segmental glomerulosclerosis (FSGS) and N=178 Minimal Change Disease (MCD) with available clinical/demographic data and 1 Hematoxylin & Eosin-stained whole slide image (WSI), were included.

Quantitative CT Scoring for Local COPD Severity.

Chronic obstructive pulmonary disease (COPD) is complex, and its course is difficult to predict due to its diverse pathophysiology. Small airway disease (SAD), a key component of COPD and potential target for emerging therapeutics, may be reversible in mild COPD, but left unchecked, may worsen, leading to airway loss and emphysema. The dual nature of SAD complicates clinical management of COPD patients, necessitating more accurate monitoring methods.

Effects of temporal lobe seizures on visual recognition memory in a non-human primate model.

Patients with temporal lobe epilepsy frequently report memory impairment, which significantly impacts their quality of life. Several studies have demonstrated an association between temporal lobe epilepsy and memory dysfunction, though the underlying mechanisms remain unclear. This study investigates whether a penicillin-induced temporal lobe seizure model in non-human primates (NHPs) replicates the recognition deficits observed in epileptic patients.

Goal-specific hippocampal inhibition gates learning.

Goal-directed navigation in a new environment requires quickly identifying and exploiting important locations. Identifying new goal locations depends on neural computations that rapidly represent locations and connect location information to key outcomes such as food. However, the mechanisms to trigger these computations at behaviourally relevant locations are not well understood.

Impact of Tissue Thickness on Computational Quantification of Features in Whole Slide Images for Diagnostic Pathology.

Tissue section thickness (TST) is an understudied variable in digital pathology that significantly impacts both visual assessments and computational analyses. This study systematically examines the effects of TST on whole slide images (WSIs) and nuclear-level features using thyroid tissue samples (n = 144) prepared at thicknesses ranging from 0.5 to 10 µm.

Viral and host factors associated with SARS-CoV-2 disease severity in Georgia, USA.

While SARS-CoV-2 vaccines have shown strong efficacy, the continued emergence of new viral variants raises concerns about the ongoing and future public health impact of COVID-19, especially in locations with suboptimal vaccination uptake. We investigated viral and host factors, including vaccination status, that were associated with SARS-CoV-2 disease severity in a setting with low vaccination rates. We analyzed clinical and demographic data from 1,957 individuals in the state of Georgia, USA, coupled with viral genome sequencing from 1,185 samples.

Computational pathology assessments of cardiac stromal remodeling: Clinical correlates and prognostic implications in heart transplantation.

Background: The hostile immune environment created by allotransplantation can accelerate pathologic tissue remodeling. Both overt and indolent inflammatory insults propel this remodeling, but there is a paucity of tools for monitoring the speed and severity of remodeling over time.

Methods: This retrospective cohort consisted of  = 2,167 digitized heart transplant biopsy slides along with records of prior inflammatory events and future allograft outcomes (cardiac death or allograft vasculopathy).

Development of CD73 Inhibitors in Tumor Immunotherapy and Opportunities in Imaging and Combination Therapy.

CD73 is a member of the membrane-bound enucleotidase family, which catalyzes the extracellular hydrolysis of adenosine monophosphate (AMP) to produce anti-inflammatory and immunosuppressive adenosine. As a novel checkpoint protein, CD73 is overexpressed in the immune system of various tumors, where adenosine is abundantly enriched. A large number of monoclonal antibodies (mAbs), nucleotides, and non-nucleotides as potent CD73 inhibitors are being discovered, providing opportunities for novel tumor immunotherapy.

Probing locus coeruleus functional network in healthy aging and its association with Alzheimer's disease biomarkers using pupillometry.

Background: Alzheimer's disease (AD) is the leading cause of dementia, and the early detection of the disease-associated changes allows early interventions. The locus coeruleus (LC) has been reported to be the first brain region to develop tau pathology in AD. However, the functional brain network of the LC in both healthy aging and AD pathology is largely unknown due to technical difficulties associated with the small size of the LC.

Structural neuroimaging abnormality and neurocognitive deficit in the first-degree relatives of schizophrenia patients (FDR) compared to the first-episode patients with schizophrenia (FEP) and healthy controls.

The existing evidence regarding structural neuroimaging alternations during the premorbid and prodromal stages of psychosis remains limited and inconsistent. Gaining a deeper insight into the morphological brain variations could potentially advance the early diagnosis of high-risk individuals for psychosis, thereby offering a clearer understanding of the underlying mechanisms that lead to the progression towards mental disorders, particularly schizophrenia. In our study, we conducted comprehensive face-to-face clinical interviews, psychiatric symptom assessments, and neurocognitive evaluation for 25 first-episode patients with schizophrenia (FEP), 35 first-degree relatives of schizophrenia patients (FDR), and 22 healthy controls (HC).

Microbial Changes Occurring During Oronasal Fistula Wound Healing.

Unlabelled: The oral microbiome is a complex community that matures with dental development and is recognized as a risk factor for systemic disease. Despite the oral cavity having a substantial microbial burden, healing of superficial oral wounds occurs quickly and with little scarring. By contrast, creation of an oro-nasal fistula (ONF), often occurring after surgery to correct a cleft palate, is a significant wound healing challenge.

Neural pathway activation in the subthalamic region depends on stimulation polarity.

Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease; however, there is limited understanding of which subthalamic pathways are recruited in response to stimulation. Here, by focusing on the polarity of the stimulus waveform (cathodic versus anodic), our goal was to elucidate biophysical mechanisms that underlie electrical stimulation in the human brain. In clinical studies, cathodic stimulation more easily triggers behavioural responses, but anodic DBS broadens the therapeutic window.

Computation-through-Dynamics Benchmark: Simulated datasets and quality metrics for dynamical models of neural activity.

A primary goal of systems neuroscience is to discover how ensembles of neurons transform inputs into goal-directed behavior, a process known as neural computation. A powerful framework for understanding neural computation uses neural dynamics - the rules that describe the temporal evolution of neural activity - to explain how goal-directed input-output transformations occur. As dynamical rules are not directly observable, we need computational models that can infer neural dynamics from recorded neural activity.

An Accelerated Spectroscopic MRI Metabolite Quantification Based on a Deep Learning Method for Radiation Therapy Planning in Brain Tumor Patients.

Background: Spectroscopic MRI (sMRI) is a quantitative imaging technique that maps infiltrated tumors in the brain without contrast injections. In a previous study (NCT03137888), sMRI-guided radiation treatment extended patient survival, showing promise for clinical translation. The spectral fitting of individual voxels in an sMRI dataset generate metabolite concentration maps that guide treatment.

Artificial intelligence in digital pathology - time for a reality check.

The past decade has seen the introduction of artificial intelligence (AI)-based approaches aimed at optimizing several workflows across many medical specialties. In clinical oncology, the most promising applications include those involving image analysis, such as digital pathology. In this Perspective, we provide a comprehensive examination of the developments in AI in digital pathology between 2019 and 2024.

Glial activation among individuals with neurological post-acute sequelae of coronavirus disease 2019: A positron emission tomography study of brain fog using [F]-FEPPA.

Background: This study examined the regional distribution of glial activation in essential workers with neurological post-acute sequelae of coronavirus disease 2019 (COVID-19) infections (N-PASC).

Methods: We injected ≤185 MBq of [F]-FEPPA as an intravenous bolus and positron-emission tomography over 2 h. To measure distribution volume (V) we recruited 24 essential workers (14 N-PASC, 10 Never-COVID-19 Controls, of whom 22 successfully placed arterial lines).

Lymphatic vessel network injury reduces local tumor control despite preservation of the tumor-draining lymph node.

The lymphatic system plays complex, often contradictory, roles in many cancers, including melanoma; these roles include contributions to tumor cell metastasis and immunosuppression in the tumor microenvironment as well as generation of antitumor immunity. Advancing our understanding of lymphatic vessel involvement in regulating tumor growth and immune response may provide new therapeutic targets or treatment plans to enhance the efficacy of existing therapies. We utilized a syngeneic murine melanoma model in which we surgically disrupted the lymphatic vessel network draining from the tumor to the tumor-draining lymph node (TDLN) while leaving the TDLN intact.

Automatic medical imaging segmentation via self-supervising large-scale convolutional neural networks.

Purpose: This study aims to develop a robust, large-scale deep learning model for medical image segmentation, leveraging self-supervised learning to overcome the limitations of supervised learning and data variability in clinical settings.

Methods And Materials: We curated a substantial multi-center CT dataset for self-supervised pre-training using masked image modeling with sparse submanifold convolution. We designed a series of Sparse Submanifold U-Nets (SS-UNets) of varying sizes and performed self-supervised pre-training.

Side- and Disease-Dependent Changes in Human Aortic Valve Cell Population and Transcriptomic Heterogeneity Determined by Single-Cell RNA Sequencing.

Background: Calcific aortic valve disease (CAVD) is a highly prevalent disease, especially in the elderly population, but there are no effective drug therapies other than aortic valve repair or replacement. CAVD develops preferentially on the fibrosa side, while the ventricularis side remains relatively spared through unknown mechanisms. We hypothesized that the fibrosa is prone to the disease due to side-dependent differences in transcriptomic patterns and cell phenotypes.

AND-gated protease-activated nanosensors for programmable detection of anti-tumour immunity.

The forward design of biosensors that implement Boolean logic to improve detection precision primarily relies on programming genetic components to control transcriptional responses. However, cell- and gene-free nanomaterials programmed with logical functions may present lower barriers for clinical translation. Here we report the design of activity-based nanosensors that implement AND-gate logic without genetic parts via bi-labile cyclic peptides.

Novel radiogenomics approach to predict and characterize pneumonitis in stage III NSCLC.

Unresectable stage III NSCLC is now treated with chemoradiation (CRT) followed by immune checkpoint inhibitors (ICI). Pneumonitis, a common CRT complication, has heightened risk with ICI, potentially causing severe outcomes. Currently, there are no biomarkers to predict pneumonitis risk or differentiate between radiation-induced pneumonitis (RTP) and ICI-induced pneumonitis (IIP).

FAK activity exacerbates disturbed flow-mediated atherosclerosis via VEGFR2-Cbl-NF-κB signaling.

Atherosclerosis develops at predictable sites in the vasculature where branch points and curvatures create non-laminar disturbed flow. This disturbed flow causes vascular inflammation by increased endothelial cell (EC) barrier permeability and the expression of inflammatory genes such as vascular cell adhesion molecule-1 (VCAM-1). Vascular endothelial growth factor receptor 2 (VEGFR2) is important for flow-induced EC inflammation; however, there are still some gaps in the signaling pathway.