Developing novel Lin28 inhibitors by computer aided drug design.

Lin28 is a key regulator of cancer stem cell gene network that promotes therapy-resistant tumor progression in various tumors. However, no Lin28 inhibitor has been approved to treat cancer patients, urging exploration of novel compounds as candidates to be tested for clinical trials. In this contribution, we applied computer-aided drug design (CADD) in combination with quantitative biochemical and biological assays.

Blarcamesine for the treatment of Early Alzheimer's Disease: Results from the ANAVEX2-73-AD-004 Phase IIB/III trial.

Background: There are no approved oral disease-modifying treatments for Alzheimer's disease (AD).

Objectives: The objective of this study was to assess efficacy and safety of blarcamesine (ANAVEX®2-73), an orally available small-molecule activator of the sigma-1 receptor (SIGMAR1) in early AD through restoration of cellular homeostasis including autophagy enhancement.

Design: ANAVEX2-73-AD-004 was a randomized, double-blind, placebo-controlled, 48-week Phase IIb/III trial.

Modified Delphi Consensus on Interventions for Acute Radiation Dermatitis in Breast Cancer: A Canadian Expert Perspective.

Acute radiation dermatitis (ARD) is a prevalent adverse effect of radiotherapy in patients with breast cancer, and there is a lack of high-quality data regarding its prevention and management. This study employs a systematic and iterative process to compile the perspectives of Canadian radiation oncology, nursing, and dermatology experts, aiming to establish consensus-based recommendations for the prevention and management of ARD in breast cancer patients. A modified Delphi consensus was conducted with the participation of 19 experts from across Canada.

Immune Biomarkers on Tissue Microarray Cores Support the Presence of Adjacent Tertiary Lymphoid Structures in Soft Tissue Sarcoma.

Immunotherapy has emerged as a new treatment modality in some soft tissue sarcomas, particularly for tumors associated with tertiary lymphoid structures (TLS). These structures are functional lymphoid aggregates, and their presence is indicative of an active anticancer immune response in the tumor microenvironment. The assessment of TLS as a predictive biomarker at scale on patient specimens remains challenging.

Carbon sink potential and the cost of afforestation in northwest China when accounting for ecosystem service value.

The cost effectiveness of mitigating climate change through afforestation needs to be evaluated for regions with a fragile environment and vulnerable ecosystems. This study develops an integrated geographic-economic-ecological framework to evaluate the cost-effectiveness of afforestation for carbon sequestration in Northwest China. It employs a spatial model of natural factors and a bioeconomic optimization model to identify marginal lands suitable for afforestation.

Sex Differences in Melanoma Survival-a GEM study.

Sex differences in melanoma are prominent, with females having a significant survival advantage. However, it is unclear why we see this survival advantage. Here we investigate the relationship between sex, clinicopathologic variables, and melanoma specific survival in 1,753 single primary melanomas from patients in the GEM study.

Agreement between methods to assess potassium intake in patients with chronic kidney disease.

Background & Aims: In the general population, 24-hour urine potassium excretion is considered the reference standard for estimating potassium intake. However, its agreement with food records and spot urine collections in adults living with chronic kidney disease (CKD) is not well-established. Given the risk of hyperkalemia related to changes in renal potassium handling, understanding if this reference standard is appropriate for the CKD population is important.

Default mode network functional connectivity as a transdiagnostic biomarker of cognitive function.

The default mode network (DMN) is intricately linked with processes such as self-referential thinking, episodic memory recall, goal-directed cognition, self-projection, and theory of mind. Over recent years, there has been a surge in examining its functional connectivity, particularly its relationship with frontoparietal networks (FPN) involved in top-down attention, executive function, and cognitive control. The fluidity in switching between these internal and external modes of processing-highlighted by anti-correlated functional connectivity-has been proposed as an indicator of cognitive health.

Preparation of crosslinked lignin-polyacrylamide hydrogel with high resistance to temperature and salinity.

In this study, we innovatively prepared a multifunctional lignin crosslinked polyacrylamide (L-cPAM) hydrogel by a sequential two-step strategy of crosslinking of lignin and crosslinked polyacrylamide (cPAM) followed by the polymerization of cPAM. The hydrogen bonding and crosslinking between the molecular chains of lignin and PAM established a rigid and porous network structure, which provided the L-cPAM hydrogel with excellent mechanical strength, thermal stability, and salinity resistance. A series of lignin dosages (0 to 30 %) were investigated during the crosslinking of lignin and PAM.

Elucidating the synergistic action between sulfonated lignin and lytic polysaccharide monooxygenases (LPMOs) in enhancing cellulose hydrolysis.

Modern enzyme cocktails often include lytic polysaccharide monooxygenase (LPMO) as an accessory enzyme that enhances cellulose accessibility during hydrolysis. Although lignin is known to generally impede cellulose hydrolysis, previous research has demonstrated lignin's potential to act as a co-factor in boosting LPMO activity and that the negative impact of lignin limiting enzyme accessibility can be mitigated by sulfonated. When sulphonated lignin was added to microcrystalline cellulose (Avicel) the activity of the lytic polysaccharide monooxygenase (LPMO) was boosted, as determined when using a quartz crystal microbalance and dissipation monitoring (QCM-D).

Quetiapine is associated with pancreatitis: A real-world pharmacovigilance study.

Quetiapine, an atypical antipsychotic widely prescribed for conditions including schizophrenia and bipolar disorder has been associated with a potential risk of pancreatitis. This study aimed to quantify the association between quetiapine use and the occurrence of pancreatitis using data from the FDA Adverse Events Reporting System. Disproportionality analyses were conducted to evaluate the frequency of pancreatitis reports linked to quetiapine compared to other drugs in the FAERS database.

Impact of comorbidities on the mortality benefits of lung cancer screening: a post-hoc analysis of PLCO and NLST trials.

Hypothesis: To evaluate how comorbidities affect mortality benefits of lung cancer screening (LCS) with low-dose computed-tomography (LDCT).

Methods: We developed a comorbidity index (PLCO-ci) using LCS-eligible participants' data from the Prostate Lung Colorectal and Ovarian (PLCO) trial (training set) and the National Lung Screening Trial (NLST) (validation set). PLCO-ci predicts 5-year non-lung cancer (LC) mortality using a regularized Cox model; with performance evaluated by the area under the ROC curve (ROC).

Differential effects of exercise training protocols on blood pressures and lipid profiles in older adults patients with hypertension: A systematic review and meta-analysis.

Decreased physical activity and high blood pressure are both risk factors for cardiovascular diseases. Controlling blood pressure within the normal range can prevent or delay these complications. This systematic review and meta-analysis analyzed the effects of different types of exercise training on the blood pressure and lipid profiles of older adults patients with hypertension.

The cold tolerance of the terrestrial slug, Ambigolimax valentianus.

Terrestrial molluscs living in temperate and polar environments must contend with cold winter temperatures. However, the physiological mechanisms underlying the survival of terrestrial molluscs in cold environments and the strategies employed by them are poorly understood. Here we investigated the cold tolerance of Ambigolimax valentianus, an invasive, terrestrial slug that has established populations in Japan, Canada, and Europe.

State of the Art in Left Atrial Appendage Occlusion.

Left atrial appendage occlusion (LAAO) has become an important therapeutic target for stroke prevention in patients with nonvalvular atrial fibrillation. Over the past 2 decades, several advancements in LAAO devices (percutaneous and surgical) have been made for stroke prevention and arrhythmia therapy. However, there are several unanswered questions regarding optimal patient selection, the preferred LAAO approach and device, the management of periprocedural and postprocedural complications, including pericardial effusion, device-related thrombus, and device leaks.

Systematic review of outcome measures used in support programs designed to enhance the functioning for autistic children and adolescents and ICF content mapping.

Purpose: 1) To identify outcome measures used in support programs designed to enhance functioning in autistic children and adolescents, and 2) To map the content of these measures to the domains of the International Classification of Functioning, Disability and Health (ICF).

Methods: A systematic review was conducted. Searches were performed in Medline/PubMed, EMBASE and Virtual Health Library databases, with no restrictions imposed regarding language or year of publication.

Machine Learning and Computed Tomography Radiomics to Predict Disease Progression to Upfront Pembrolizumab Monotherapy in Advanced Non-Small-Cell Lung Cancer: A Pilot Study.

Background/objectives: Pembrolizumab monotherapy is approved in Canada for first-line treatment of advanced NSCLC with PD-L1 ≥ 50% and no EGFR/ALK aberrations. However, approximately 55% of these patients do not respond to pembrolizumab, underscoring the need for the early intervention of non-responders to optimize treatment strategies. Distinguishing the 55% sub-cohort prior to treatment is a real-world dilemma.

Cannabinoids: Role in Neurological Diseases and Psychiatric Disorders.

An impact of legalization and decriminalization of marijuana is the gradual increase in the use of cannabis for recreational purposes, which poses a potential threat to society and healthcare systems worldwide. However, the discovery of receptor subtypes, endogenous endocannabinoids, and enzymes involved in synthesis and degradation, as well as pharmacological characterization of receptors, has led to exploration of the use of cannabis in multiple peripheral and central pathological conditions. The role of cannabis in the modulation of crucial events involving perturbed physiological functions and disease progression, including apoptosis, inflammation, oxidative stress, perturbed mitochondrial function, and the impaired immune system, indicates medicinal values.

The Accuracy of the Passive Leg Raising Test Using the Perfusion Index to Identify Preload Responsiveness-A Single Center Study in a Resource-Limited Setting.

We investigated the accuracy of predicting preload responsiveness by means of a passive leg raising test (PLR) using the perfusion index (PI) in critically ill patients showing signs of hypoperfusion in a resource-limited setting. We carried out a prospective observational single center study in patients admitted for sepsis or severe malaria with signs of hypoperfusion in Chattogram, Bangladesh. A PLR was performed at baseline, and at 6, 24, 48, and 72 h.

A High-Quality Phased Genome Assembly of Stinging Nettle ( ssp. ).

Stinging nettles () have a long history of association with human civilization, having been used as a source of textile fibers, food and medicine. Here, we present a chromosome-level, phased genome assembly for a diploid female clone of from Romania. Using a combination of PacBio HiFi, Oxford Nanopore, and Illumina sequencing, as well as Hi-C long-range interaction data (using a novel Hi-C protocol presented here), we assembled two haplotypes of 574.

Considerations for adapting digital competencies and training approaches to the public health workforce: an interpretive description of practitioners' perspectives in Canada.

Background: Widespread digital transformation necessitates developing digital competencies for public health practice. Given work in 2024 to update Canada's public health core competencies, there are opportunities to consider digital competencies. In our previous research, we identified digital competency and training recommendations within the literature.

A prospective multi-site study to evaluate the performance and usability of an oral fluid-based HIV self-test in Canada.

Background: Blood and oral fluid-based HIV self-tests are important for reaching the undiagnosed living with HIV. The study objectives were to evaluate the oral fluid-based OraQuick® HIV Self-Test (HIV-ST) performance in comparison to laboratory reference testing; determine if laypersons can correctly perform the HIV-ST; document if intended users can successfully interpret pre-made contrived positive, negative, and invalid results; and document if intended users can understand the key messages in the product labeling.

Methods: This prospective study enrolled consenting adult intended users of HIV self-testing from six community health centres in four Canadian provinces between June 2022 and January 2024.