Graphical models for identifying pore-forming proteins.

Pore-forming toxins (PFTs) are proteins that form lesions in biological membranes. Better understanding of the structure and function of these proteins will be beneficial in a number of biotechnological applications, including the development of new pest control methods in agriculture. When searching for new pore formers, existing sequence homology-based methods fail to discover truly novel proteins with low sequence identity to known proteins.

Analysis of reasons for medical malpractice litigation due to anterior cervical discectomy and fusion.

Background: Anterior cervical discectomy and fusions (ACDF) are among the most common cervical spine operations, with over 137,000 surgeries performed annually. Understanding reasons underlying malpractice pertaining to ACDF may inform physicians of practices to improve delivery of patient care and mitigate malpractice. The aim of our study was to analyze the causes and outcomes for lawsuits pertaining to ACDF.

Can artificial intelligence reach human thought?

The transformative achievements of deep learning have led several scholars to raise the question of whether artificial intelligence (AI) can reach and then surpass the level of human thought. Here, after addressing methodological problems regarding the possible answer to this question, it is argued that the definition of intelligence proposed by proponents of the AI as "the ability to accomplish complex goals," is appropriate for machines but does not capture the essence of human thought. After discussing the differences regarding understanding between machines and the brain, as well as the importance of subjective experiences, it is emphasized that most proponents of the eventual superiority of AI ignore the importance of the on the brain, the of the brain, and the vital role of the glia cells.

Theta-frequency medial septal nucleus deep brain stimulation increases neurovascular activity in MK-801-treated mice.

Introduction: Deep brain stimulation (DBS) has shown remarkable success treating neurological and psychiatric disorders including Parkinson's disease, essential tremor, dystonia, epilepsy, and obsessive-compulsive disorder. DBS is now being explored to improve cognitive and functional outcomes in other psychiatric conditions, such as those characterized by reduced N-methyl-D-aspartate (NMDA) function (i.e.

Integrating a Fundus Camera with High-Frequency Ultrasound for Precise Ocular Lesion Assessment.

Ultrasound A-scan is an important tool for quantitative assessment of ocular lesions. However, its usability is limited by the difficulty of accurately localizing the ultrasound probe to a lesion of interest. In this study, a transparent LiNbO single crystal ultrasound transducer was fabricated, and integrated with a widefield fundus camera to guide the ultrasound local position.

Diffusion MRI harmonization via personalized template mapping.

One fundamental challenge in diffusion magnetic resonance imaging (dMRI) harmonization is to disentangle the contributions of scanner-related effects from the variable brain anatomy for the observed imaging signals. Conventional harmonization methods rely on establishing an atlas space to resolve anatomical variability and generate a unified inter-site mapping function. However, this approach is limited in accounting for the misalignment of neuroanatomy that still widely persists even after registration, especially in regions close to cortical boundaries.

Event detection and classification from multimodal time series with application to neural data.

The detection of events in time-series data is a common signal-processing problem. When the data can be modeled as a known template signal with an unknown delay in Gaussian noise, detection of the template signal can be done with a traditional matched filter. However, in many applications, the event of interest is represented in multimodal data consisting of both Gaussian and point-process time series.

Uncovering Heterogeneity in Alzheimer's Disease from Graphical Modeling of the Tau Spatiotemporal Topography.

Growing evidence from post-mortem and in vivo studies have demonstrated the substantial variability of tau pathology spreading patterns in Alzheimer's disease(AD). Automated tools for characterizing the heterogeneity of tau pathology will enable a more accurate understanding of the disease and help the development of targeted treatment. In this paper, we propose a Reeb graph representation of tau pathology topography on cortical surfaces using tau PET imaging data.

IHMCIF: An Extension of the PDBx/mmCIF Data Standard for Integrative Structure Determination Methods.

IHMCIF (github.com/ihmwg/IHMCIF) is a data information framework that supports archiving and disseminating macromolecular structures determined by integrative or hybrid modeling (IHM), and making them Findable, Accessible, Interoperable, and Reusable (FAIR). IHMCIF is an extension of the Protein Data Bank Exchange/macromolecular Crystallographic Information Framework (PDBx/mmCIF) that serves as the framework for the Protein Data Bank (PDB) to archive experimentally determined atomic structures of biological macromolecules and their complexes with one another and small molecule ligands (e.

Personalized Patch-based Normality Assessment of Brain Atrophy in Alzheimer's Disease.

Cortical thickness is an important biomarker associated with gray matter atrophy in neurodegenerative diseases. In order to conduct meaningful comparisons of cortical thickness between different subjects, it is imperative to establish correspondence among surface meshes. Conventional methods achieve this by projecting surface onto canonical domains such as the unit sphere or averaging feature values in anatomical regions of interest (ROIs).

Shape-Aware 3D Small Vessel Segmentation with Local Contrast Guided Attention.

The automated segmentation and analysis of small vessels from imaging data is an important task for many clinical applications. While current filtering and learning methods have achieved good performance on the segmentation of large vessels, they are sub-optimal for small vessel detection due to their apparent geometric irregularity and weak contrast given the relatively limited resolution of existing imaging techniques. In addition, for supervised learning approaches, the acquisition of accurate pixel-wise annotations in these small vascular regions heavily relies on skilled experts.

FASSt : Filtering via Symmetric Autoencoder for Spherical Superficial White Matter Tractography.

Superficial white matter (SWM) plays an important role in functioning of the human brain, and it contains a large amount of cortico-cortical connections. However, the difficulties of generating complete and reliable U-fibers make SWM-related analysis lag behind relatively matured Deep white matter (DWM) analysis. With the aid of some newly proposed surface-based SWM tractography algorithms, we have developed a specialized SWM filtering method based on a symmetric variational autoencoder (VAE).

New insights into grocery store visits among east Los Angeles residents using mobility data.

In this study, we employed spatially aggregated population mobility data, generated from mobile phone locations in 2021, to investigate patterns of grocery store visits among residents east and northeast of Downtown Los Angeles, in which 60% of the census tracts had previously been designated as "food deserts". Further, we examined whether the store visits varied with neighborhood sociodemographics and grocery store accessibility. We found that residents averaged 0.

Identification and Connectomic Profiling of Concussion Using Bayesian Machine Learning.

Accurate early diagnosis of concussion is useful to prevent sequelae and improve neurocognitive outcomes. Early after head impact, concussion diagnosis may be doubtful in persons whose neurological, neuroradiological, and/or neurocognitive examinations are equivocal. Such individuals can benefit from novel accurate assessments that complement clinical diagnostics.

Intervention to promote preventive dental care for older Korean-American Medi-Cal enrollees in Los Angeles.

Background: In California, preventive dental care is covered by Medi-Cal (California's Medicaid program). However, many beneficiaries do not use their dental benefits. Given that a lack of knowledge about oral health and insurance coverage contributes to this underutilization, promoting the use of dental benefits among eligible individuals via an educational program is imperative.

Effect of mobile food environments on fast food visits.

Poor diets are a leading cause of morbidity and mortality. Exposure to low-quality food environments saturated with fast food outlets is hypothesized to negatively impact diet. However, food environment research has predominantly focused on static food environments around home neighborhoods and generated mixed findings.

Programming Juxtacrine-Based Synthetic Signaling Networks in a Cellular Potts Framework.

Synthetic development is a synthetic biology subfield aiming to reprogram higher-order eukaryotic cells for tissue formation and morphogenesis. Reprogramming efforts commonly rely upon implementing custom signaling networks into these cells, but the efficient design of these signaling networks is a substantial challenge. It is difficult to predict the tissue/morphogenic outcome of these networks, and in vitro testing of many networks is both costly and time-consuming.

Real-Time Autophagic Flux Measurements in Live Cells Using a Novel Fluorescent Marker DAPRed.

Autophagy is a conserved homeostatic mechanism involved in cellular homeostasis and many disease processes. Although it was first described in yeast cells undergoing starvation, we have learned over the years that autophagy gets activated in many stress conditions and during development and aging in mammalian cells. Understanding the fundamental mechanisms underlying autophagy effects can bring us closer to better insights into the pathogenesis of many disease conditions (e.

Functional ultrasound imaging of the human spinal cord.

Utilizing the first in-human functional ultrasound imaging (fUSI) of the spinal cord, we demonstrate the integration of spinal functional responses to electrical stimulation. We record and characterize the hemodynamic responses of the spinal cord to a neuromodulatory intervention commonly used for treating pain and increasingly used for the restoration of sensorimotor and autonomic function. We found that the hemodynamic response to stimulation reflects a spatiotemporal modulation of the spinal cord circuitry not previously recognized.

NOTCH localizes to mitochondria through the TBC1D15-FIS1 interaction and is stabilized via blockade of E3 ligase and CDK8 recruitment to reprogram tumor-initiating cells.

The P53-destabilizing TBC1D15-NOTCH protein interaction promotes self-renewal of tumor-initiating stem-like cells (TICs); however, the mechanisms governing the regulation of this pathway have not been fully elucidated. Here, we show that TBC1D15 stabilizes NOTCH and c-JUN through blockade of E3 ligase and CDK8 recruitment to phosphodegron sequences. Chromatin immunoprecipitation (ChIP-seq) analysis was performed to determine whether TBC1D15-dependent NOTCH1 binding occurs in TICs or non-TICs.

Hydroxypropyl-Beta Cyclodextrin Barrier Prevents Respiratory Viral Infections: A Preclinical Study.

The emergence and mutation of pathogenic viruses have been occurring at an unprecedented rate in recent decades. The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed into a global public health crisis due to extensive viral transmission. In situ RNA mapping has revealed angiotensin-converting enzyme 2 (ACE2) expression to be highest in the nose and lower in the lung, pointing to nasal susceptibility as a predominant route for infection and the cause of subsequent pulmonary effects.

Fasting-mimicking diet causes hepatic and blood markers changes indicating reduced biological age and disease risk.

In mice, periodic cycles of a fasting mimicking diet (FMD) protect normal cells while killing damaged cells including cancer and autoimmune cells, reduce inflammation, promote multi-system regeneration, and extend longevity. Here, we performed secondary and exploratory analysis of blood samples from a randomized clinical trial (NCT02158897) and show that 3 FMD cycles in adult study participants are associated with reduced insulin resistance and other pre-diabetes markers, lower hepatic fat (as determined by magnetic resonance imaging) and increased lymphoid to myeloid ratio: an indicator of immune system age. Based on a validated measure of biological age predictive of morbidity and mortality, 3 FMD cycles were associated with a decrease of 2.

Cancer-related cells and oncosomes in the liquid biopsy of pancreatic cancer patients undergoing surgery.

Pancreatic ductal adenocarcinoma (PDAC) has a five-year survival rate of less than 10% due to its late diagnosis, rapid metastasis, and chemotherapeutic resistance. For a small proportion (10-20%) of early-stage patients however, surgical resection of the pancreatic tumor offers the best chance for survival but the effect of surgery on disease dissemination is unknown. The primary objective of this study was to characterize cellular and acellular blood-based analytes in portal and peripheral blood before pancreatic manipulation, during tumor dissection and immediately after surgical resection to determine the effects of the surgery.