Functional Brain Network Classification for Alzheimer’s Disease Detection with Deep Features and Extreme Learning Machine

The human brain can be inherently modeled as a brain network, where nodes denote billions of neurons and edges denote massive connections between neurons.     

Assessment of toxicity using dehydrogenases activity and mathematical modeling

Dehydrogenase activity is frequently used to assess the general condition of microorganisms in soil and activated sludge. Many studies have investigated the inhibition of dehydrogenase activity by various compounds, including heavy metal ions. However, the time after which the measurements are carried out is often chosen arbitrarily. Thus, it can be difficult to estimate how the toxic effects of compounds vary during the reaction and when the maximum of the effect would be reached. Hence, the aim of this study was to create simple and useful mathematical model describing changes in dehydrogenase activity during exposure to substances that inactivate enzymes. Our model is based on the Lagergrens pseudo-first-order equation, the rate of chemical reactions, enzyme activity, and inactivation and was created to describe short-term changes in dehydrogenase activity. The main assumption of our model is that toxic substances cause irreversible inactivation of enzyme units. The model is able to predict the maximum direct toxic effect (MDTE) and the time to reach this maximum (T_MDTE). In order to validate our model, we present two examples: inactivation of dehydrogenase in microorganisms in soil and activated sludge. The model was applied successfully for cadmium and copper ions. Our results indicate that the predicted MDTE and T_MDTE are more appropriate than EC₅₀ and IC₅₀ for toxicity assessments, except for long exposure times.     

Necroptotic TNFα-Syndecan 4-TNFα Vicious Cycle as a Therapeutic Target for Preventing Temporomandibular Joint Osteoarthritis

Temporomandibular joint osteoarthritis (TMJOA) is a chronic degenerative disease for which the underlying mechanism still remains unclear. Compared with apoptosis and autophagy, necroptosis causes greater harm to tissue homeostasis by releasing damage-associated molecular patterns (DAMPs). However, the role of necroptosis and downstream key DAMPs in TMJOA is unknown. Here, rodent models of TMJOA were established by the unilateral anterior crossbite (UAC). Transmission electron microscopy (TEM) and immunohistochemistry of receptor interacting protein kinase 3 (RIPK3)/phosphorylation of mixed lineage kinase domain-like protein (pMLKL) were conducted to evaluate the occurrence of necroptosis in vivo. The therapeutic effects of blocking necroptosis were achieved by intra-articularly injecting RIPK3 or MLKL inhibitors and using RIPK3 or MLKL knockout mice. In vitro necroptosis of condylar chondrocyte was induced by combination of tumor necrosis factor alpha (TNFα), second mitochondria-derived activator of caspases (SMAC) mimetics and carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]- fluoromethylketone (z-VAD-fmk). The possible DAMPs released by necroptotic chondrocytes were screened by quantitative proteomics and blocked by specific antibody. Translucent cytosol, swollen organelles, and ruptured cell membranes, features of necroptosis, were frequently manifested in chondrocytes at the early stage of condylar cartilage degeneration in TMJOA, which was accompanied by upregulation of RIPK3/pMLKL. Inhibiting or knocking out RIPK3/MLKL significantly prevented cartilage degeneration. DAMPs released by necroptotic condylar chondrocytes, such as syndecan 4 (SDC4) and heat shock protein 90 (HSP90), were verified. Furthermore, blocking the function of SDC4 significantly attenuated the expression of TNFα in cartilage and synovium, and accordingly increased cartilage thickness and reduced synovial inflammation. Thus, the necroptotic vicious cycle of TNFα-SDC4-TNFα contributes to cartilage degeneration and synovitis, and can serve as a potential therapeutic target for treating TMJOA. © 2022 American Society for Bone and Mineral Research (ASBMR).     

Quality of decision aids developed for women at average risk of breast cancer eligible for mammographic screening: Systematic review and assessment according to the International Patient Decision Aid Standards instrument

Mammographic screening contributes to a reduction in specific mortality, but it has disadvantages. Decision aids are tools designed to support people's decisions. Because these aids influence patient choice, their quality is crucial. The objective of the current study was to conduct a systematic review of decision aids developed for women eligible for mammographic screening who have an average breast cancer risk and to assess the quality of these aids. The systematic review included articles published between January 1, 1997, and August 1, 2019, in the PubMed, Embase, Cochrane, and PsycInfo databases. The studies were reviewed independently by 2 reviewers. Any study containing a decision aid for women eligible for mammographic screening with an average breast cancer risk was included. Two double-blind reviewers assessed the quality of the selected decision aids using the International Patient Decision Aid Standards instrument, version 3 (IPDASi). Twenty-three decision aids were extracted. Classification of decision aid quality using the IPDASi demonstrated large variations among the decision aids (maximum IPDASi score, 188; mean ± SD score, 132.6 ± 23.8; range, 85-172). Three decision aids had high overall scores. The 3 best-rated dimensions were disclosure (maximum score, 8; mean score, 6.8), focusing on transparency; information (maximum score, 32; mean score, 26.1), focusing on the provision of sufficient details; and probabilities (maximum score, 32; mean score 25), focusing on the presentation of probabilities. The 3 lowest-rated dimensions were decision support technology evaluation (maximum score, 8; mean score, 4.3), focusing on the effectiveness of the decision aid; development (maximum score, 24; mean score, 12.6), evaluating the development process; and plain language (maximum score, 4; mean score, 1.9), assessing appropriateness for patients with low literacy. The results of this review identified 3 high-quality decision aids for breast cancer screening.