Ultrasensitive Detection of Blood-Based Alzheimer's Disease Biomarkers: A Comprehensive SERS-Immunoassay Platform Enhanced by Machine Learning.

Accurate and early disease detection is crucial for improving patient care, but traditional diagnostic methods often fail to identify diseases in their early stages, leading to delayed treatment outcomes. Early diagnosis using blood derivatives as a source for biomarkers is particularly important for managing Alzheimer's disease (AD). This study introduces a novel approach for the precise and ultrasensitive detection of multiple core AD biomarkers (Aβ, Aβ, p-tau, and t-tau) using surface-enhanced Raman spectroscopy (SERS) combined with machine-learning algorithms.

Nanoscopically Confined 1,4-Polybutadiene Melts: Exploring Confinement by Alumina Nanorod and Nanopore Systems.

We present molecular dynamics simulations of a chemically realistic model of 1,4-polybutadiene (PBD) in contact with curved alumina surfaces. We contrast the behavior of PBD infiltrated into alumina pores with a curvature radius of about three times the radius of gyration of the chains to its behavior next to a melt dispersed alumina rod of equal absolute curvature. These confinement types represent situations occurring in polymer melts loaded with nanoparticles due to nanoparticle aggregation.

Efficient scar-free knock-ins of several kilobases in plants by engineered CRISPR-Cas endonucleases.

In plants and mammals, non-homologous end-joining is the dominant pathway to repair DNA double-strand breaks, making it challenging to generate knock-in events. In this study, we identified two groups of exonucleases from the herpes virus and the bacteriophage T7 families that conferred an up to 38-fold increase in homology-directed repair frequencies when fused to Cas9/Cas12a in a tobacco mosaic virus-based transient assay in Nicotiana benthamiana. We achieved precise and scar-free insertion of several kilobases of DNA both in transient and stable transformation systems.

Reverse Mapping of Coarse Grained Polyglutamine Conformations from PRIME20 Sampling.

An inverse coarse-graining protocol is presented for generating and validating atomistic structures of large (bio-) molecules from conformations obtained via a coarse-grained sampling method. Specifically, the protocol is implemented and tested based on the (coarse-grained) PRIME20 protein model (P20/SAMC), and the resulting all-atom conformations are simulated using conventional biomolecular force fields. The phase space sampling at the coarse-grained level is performed with a stochastical approximation Monte Carlo approach.

"I'm still not over feeling so isolated": Métis women, Two-Spirit, and gender-diverse people's experiences of the COVID-19 pandemic.

Objectives: The aim of this study was to explore and learn from the experiences of Métis women, Two-Spirit, and gender-diverse people accessing health and social services in Victoria, British Columbia, during the COVID-19 pandemic.

Methods: This paper comes from a larger study exploring Métis women, Two-Spirit, and gender-diverse people's experiences accessing health and social services in Victoria. Using a by-and-for Métis approach that employed a conversational interview method, we conducted interviews with Métis women, Two-Spirit, and gender-diverse people who lived in and/or accessed services in Victoria in December 2020 and January 2021.

Novel lactoferrin-conjugated gallium complex to treat Pseudomonas aeruginosa wound infection.

Pseudomonas aeruginosa is one of the leading causes of opportunistic infections such as chronic wound infection that could lead to multiple organ failure and death. Gallium (Ga) ions are known to inhibit P. aeruginosa growth and biofilm formation but require carrier for localized controlled delivery.

"I would love for there not to be so many hoops … ": recommendations to improve abortion service access and experiences made by Indigenous women and 2SLGTBQIA+ people in Canada.

Acknowledging the barriers in accessing sexual and reproductive health services that disproportionately impact Indigenous women and 2SLGTBQIA+ people, coupled with the lack of knowledge surrounding Indigenous peoples' experiences with abortion, we present qualitative findings from a pilot study investigating Indigenous experiences of accessing abortion services in Canada. We focus on findings related to participant recommendations for improving safety and accessibility of abortion services made by and for Indigenous people in Canada. Informed by an Indigenous Advisory Committee consisting of front-line service providers working in the area of abortion service access and/ or support across Canada, the research team applied an Indigenous methodology to engage with 15 Indigenous people across Canada utilising a conversational interview method, between September and November 2021.

'By identifying myself as Métis, I didn't feel safe…': Experiences of navigating racism and discrimination among Métis women, Two-Spirit and gender diverse community members in Victoria, Canada.

Objective: Racism acts as a major barrier to accessing health services for Indigenous communities in Canada, often leading to delayed, avoided or lack of treatment altogether. The Métis population is uniquely positioned in urban settings, as they experience discrimination from both Indigenous and mainstream health and social services due to Canada's long colonial history that is ongoing. Yet, Métis are often left out of discussions regarding racism and health service access.

Accuracy of Artificial Intelligence in Estimating Best-Corrected Visual Acuity From Fundus Photographs in Eyes With Diabetic Macular Edema.

Importance: Best-corrected visual acuity (BCVA) is a measure used to manage diabetic macular edema (DME), sometimes suggesting development of DME or consideration of initiating, repeating, withholding, or resuming treatment with anti-vascular endothelial growth factor. Using artificial intelligence (AI) to estimate BCVA from fundus images could help clinicians manage DME by reducing the personnel needed for refraction, the time presently required for assessing BCVA, or even the number of office visits if imaged remotely.

Objective: To evaluate the potential application of AI techniques for estimating BCVA from fundus photographs with and without ancillary information.

Improved prime editing allows for routine predictable gene editing in Physcomitrium patens.

Efficient and precise gene editing is the gold standard of any reverse genetic study. The recently developed prime editing approach, a modified CRISPR/Cas9 [clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein] editing method, has reached the precision goal but its editing rate can be improved. We present an improved methodology that allows for routine prime editing in the model plant Physcomitrium patens, whilst exploring potential new prime editing improvements.

A qualitative study exploring access barriers to abortion services among Indigenous Peoples in Canada.

Objective: This paper reports on findings from our exploratory qualitative study that aims to advance knowledge around access to and experiences with abortion services among Indigenous Peoples in Canada.

Study Design: We applied an Indigenous methodology to engage with 15 Indigenous Peoples across Canada utilizing a conversational interview method. Our study was informed by an Indigenous Advisory Committee consisting of front-line service providers working in the area of abortion service access and/ or support across Canada.

"Organized stress" for robust scale-up of intensified production process with fed-batch seed bioreactor.

Process intensification has been widely used for many years in the mammalian biomanufacturing industry to increase productivity, agility and flexibility while reducing production costs. The most commonly used intensified processes are operated using a perfusion or fed-batch seed bioreactor enabling a higher than usual seeding density in the fed-batch production bioreactor. Hence, as part of the growth phase is shifted to the seed bioreactor, there is a lower split ratio, which increases the criticality of the seed bioreactor and could impact production performance.

Aggregation and crystallization of small alkanes.

We present a computer simulation study of the aggregation and ordering of short alkane chains using a united atom model description. Our simulation approach allows us to determine the density of states of our systems and, from those, their thermodynamics for all temperatures. All systems show a first order aggregation transition followed by a low-temperature ordering transition.

A novel binary pesticidal protein from Chryseobacterium arthrosphaerae controls western corn rootworm by a different mode of action to existing commercial pesticidal proteins.

The western corn rootworm (WCR) Diabrotica virgifera virgifera (Coleoptera: Chrysomelidae) remains one of the economically most important pests of maize (Zea mays) due to its adaptive capabilities to pest management options. This includes the ability to develop resistance to some of the commercial pesticidal proteins originating from different strains of Bacillus thuringiensis. Although urgently needed, the discovery of new, environmentally safe agents with new modes of action is a challenge.

Integrating simulation models and statistical models using causal modelling principles to predict aquatic macroinvertebrate responses to climate change.

Climate change is projected to threaten ecological communities through changes in temperature, rainfall, runoff patterns, and mediated changes in other environmental variables. Their combined effects are difficult to comprehend without the mathematical machinery of causal modelling. Using piecewise structural equation modelling, we aim to predict the responses of aquatic macroinvertebrate total abundance and richness to disturbances generated by climate change.

The Pain of Residential Schools in Canada: An Analysis of Silence and Narrative.

In operation for over a century, the Indian Residential School system is a painful part of Canadian history. Through the theoretical approaches to pain envisioned by Elaine Scarry, Javier Moscoso, and Ilit Ferber, this article examines how the pain of residential school experiences manifests as silence among residential school survivors. Through a close analysis of narratives that break free from that silence, it becomes apparent that narrative offers one path to national reconciliation.

Structure and dynamics of a 1,4-polybutadiene melt in an alumina nanopore: A molecular dynamics simulation.

We present results of molecular dynamics simulations of a chemically realistic model of 1,4-polybutadiene confined in a cylindrical alumina nanopore of diameter 10 nm. The simulations are done at three different temperatures above the glass transition temperature T. We investigate the density layering across the nanopore as well as the orientational ordering in the polymer melt, brought about by the confinement, on both the segmental and chain scales.

Thermodynamics and Conformations of Single Polyalanine, Polyserine, and Polyglutamine Chains within the PRIME20 Model.

Understanding the conformational behavior of proteins has been a long-standing challenge to which computer simulations could contribute significantly. This concerns the folding behavior of proteins as well as the conformational statistics of intrinsically disordered proteins. A well-converged sampling of the conformational statistics over a broad range of control parameters is computationally extremely challenging and best addressed by coarse-grained modeling, for example, with an intermediate resolution model like the PRIME20 model.

Role of torsional potential in chain conformation, thermodynamics, and glass formation of simulated polybutadiene melts.

For polymer chains, the torsional potential is an important intramolecular energy influencing chain flexibility and segmental dynamics. Through molecular dynamics simulations of an atomistic model for melts of cis-trans-1,4-polybutadiene (PBD), we explore the effect of the torsions on conformational properties (bond vector correlations and mean-square internal distances), fundamental thermodynamic quantities (density, compressibility, internal energy, and specific heat), and glass transition temperature T. This is achieved by systematically reducing the strength of the torsional potential, starting from the chemically realistic chain (CRC) model with the full potential toward the freely rotating chain (FRC) model without the torsional potential.

Gallium-Curcumin Nanoparticle Conjugates as an Antibacterial Agent against : Synthesis and Characterization.

Combating antibiotic resistance has found great interest in the current clinical scenario. , an opportunistic multidrug-resistant pathogen, is well known for its deadly role in hospital-acquired infections. Infections by are among the toughest to treat because of its intrinsic and acquired resistance to antibiotics.

TARA: Training and Representation Alteration for AI Fairness and Domain Generalization.

We propose a novel method for enforcing AI fairness with respect to protected or sensitive factors. This method uses a dual strategy performing training and representation alteration (TARA) for the mitigation of prominent causes of AI bias. It includes the use of representation learning alteration via adversarial independence to suppress the bias-inducing dependence of the data representation from protected factors and training set alteration via intelligent augmentation to address bias-causing data imbalance by using generative models that allow the fine control of sensitive factors related to underrepresented populations via domain adaptation and latent space manipulation.

Detecting Anomalies in Retinal Diseases Using Generative, Discriminative, and Self-supervised Deep Learning.

Importance: Anomaly detectors could be pursued for retinal diagnoses based on artificial intelligence systems that may not have access to training examples for all retinal diseases in all phenotypic presentations. Possible applications could include screening of population for any retinal disease rather than a specific disease such as diabetic retinopathy, detection of novel retinal diseases or novel presentations of common retinal diseases, and detection of rare diseases with little or no data available for training.

Objective: To study the application of anomaly detection to retinal diseases.

Least kth-Order and Rényi Generative Adversarial Networks.

We investigate the use of parameterized families of information-theoretic measures to generalize the loss functions of generative adversarial networks (GANs) with the objective of improving performance. A new generator loss function, least kth-order GAN (LkGAN), is introduced, generalizing the least squares GANs (LSGANs) by using a kth-order absolute error distortion measure with k≥1 (which recovers the LSGAN loss function when k=2). It is shown that minimizing this generalized loss function under an (unconstrained) optimal discriminator is equivalent to minimizing the kth-order Pearson-Vajda divergence.

Quantifying Discharge Medication Reconciliation Errors at 2 Pediatric Hospitals.

Introduction: Medication reconciliation errors (MREs) are common and can lead to significant patient harm. Quality improvement efforts to identify and reduce these errors typically rely on resource-intensive chart reviews or adverse event reporting. Quantifying these errors hospital-wide is complicated and rarely done.