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INTRODUCTION: We aimed to compare whether the visualisation provided by arthroscopic hyperflexion and Figure 4 has an effect on femoral tunnel placement in patients undergoing single bundle Anterior Cruciate Ligament Reconstruction (ACLR). MATERIALS AND METHODS: We retrospectively evaluated 93 patients who underwent single-band ACLR for Anterior Cruciate Ligament (ACL) injury between 2016 and 2019. Eighty patients met the inclusion criteria with a minimum follow-up of 12 months. We divided the patients into Group 1 (figure 4) and Group 2 (hyperflexion). We analysed the demographic, radiological and functional outcomes of the patients. The functional Lysholm score, operative time, radiological Quadrant method (% proximal-distal and % anterior-posterior) measurements, tunnel lengths, axial and coronal plane angles, and iatrogenic chondral injury in the medial femoral condyle were evaluated. RESULTS: Iatrogenic chondral injury developed in the medial femoral condyle in a total of seven patients in both groups: one patient in group 1 (Figure 4) and six patients in group 2 (Hyperflexion). Although statistically insignificant, iatrogenic medial femoral condyle damage was less in group 1. The statistical analysis between surgical operation time (p = 0.046) and tunnel lengths (p = 0.042) was significant. CONCLUSION: The position of figure 4 provides visualisation of lateral intercondylar notch better than hyperflexion. In the reaming stage, the medial femoral condyle is less damaged in group 1 (Figure 4). In ACLR, which has a long learning curve, short surgery time is seen as an important advantage for surgeons who have just started doing ACLR. We think that it can be used as an alternative method to hyperflexion in the learning process and maybe shorten the learning curve process.

Dentists and denture wearers have reported that the regular use of a denture cleanser causes whitening of dentures. The whitening effect of denture cleansers on acrylic resin dentures was investigated using four different types of agents on six different types of acrylic resin discs. The color values of the samples were measured using a reflectometer. The greatest whitening effect was seen on autopolymerizing acrylic resins for one of the denture cleansers with all the resins tested. [ABSTRACT FROM AUTHOR]

This in vitro study investigated the effect of the major connector on distal abutment tooth and denture base movements when loads were applied to a partial denture with extracoronal attachments. A brass mechanism was constructed for load application, and the abutment and base movements were measured in three planes using a kinesiograph. It was determined that cutting the major connector affected the degree of abutment tooth movement but not the direction. After cutting the major connector, the base movement increased in all three planes with the different forces applied. The direction of the base movement changed only in the buccolingual plane. [ABSTRACT FROM AUTHOR]

Five titanium caps were implanted in the mandibles of five dogs. Three caps contained Sm-Co mini magnets and two caps were empty. The aim of this study was to determine if implanted magnetic fields had any biological effects on the bone tissue of dogs. At the end of 6 months, the animals were sacrificed and segments containing implants and segments from the side opposite the implants, for control, were removed. Sections were made from the specimens and no pathology was seen upon microscopic examination. [ABSTRACT FROM AUTHOR]

Drawing upon an extensive dataset comprising 3,680 cyberattacks on firms listed in 5 stock markets, our main objective is to ascertain the financial market reaction based on a hybrid valuation inspired by the event study methodology and a counterfactual analysis. Analyses concern three dates that are specific to cyberattacks: 1) the accident date; 2) the first notice date; and 3) the original loss start date. Results indicate that there is a negative abnormal return for the NASDAQ after the accident date. The reactions of the NASDAQ and NYSE are similar, and negative for the first notice date but positive after the original loss start date. In the European context, cumulative abnormal returns are negative for French and German companies after the first notice date.

Subject of the present investigation is the elastic-plastic rotating annular disk having a rigid casing. The plane state of stress is considered for two different boundary conditions: a) inner surface with constraint, allowing no motion in the radial direction, b) free inner surface without radial stress. The analysis is based on Tresca's yield condition, its associated flow rule, and linear strain hardening material behaviour. For both cases, closed form solutions are obtained and numerical results are presented. It is shown that the influence of hardening parameter on the elastic-plastic interface radii is very small, for fixed boundary conditions. [ABSTRACT FROM AUTHOR]

Collagen VI-related dystrophies (COL6RD) are a group of rare muscle disorders caused by mutations in specific genes responsible for type VI collagen production. It affects muscles, joints, and connective tissues, leading to weakness, joint problems, and structural issues. Currently, there is no effective treatment for COL6RD; its management typically addresses symptoms and complications. Therefore, it is essential to decipher the disease's molecular mechanisms, identify drug targets, and develop effective treatment strategies to treat COL6RD. In this study, we employed differential gene expression analysis, weighted gene co-expression network analysis, and genome-scale metabolic modeling to investigate gene expression patterns in COL6RD patients, uncovering key genes, significant metabolites, and disease-related pathophysiological pathways. First, we performed differential gene expression and weighted gene co-expression network analyses, which led to the identification of 12 genes ( CHCHD10 , MRPS24 , TRIP10 , RNF123 , MRPS15 , NDUFB4 , COX10 , FUNDC2 , MDH2 , RPL3L , NDUFB11 , PARVB ) as potential hub genes involved in the disease. Second, we utilized a drug repurposing strategy to identify pharmaceutical candidates that could potentially modulate these genes and be effective in the treatment. Next, we utilized context-specific genome-scale metabolic models to compare metabolic variations between healthy individuals and COL6RD patients. Finally, we conducted reporter metabolite analysis to identify reporter metabolites (e.g., phosphatidates, nicotinate ribonucleotide, ubiquinol, ferricytochrome C). In summary, our analysis revealed critical genes and pathways associated with COL6RD and identified potential targets, reporter metabolites, and candidate drugs for therapeutic interventions.

Alzheimer's disease (AD) is a debilitating neurodegenerative disorder with a global impact, yet its pathogenesis remains poorly understood. While age, metabolic abnormalities, and accumulation of neurotoxic substances are potential risk factors for AD, their effects are confounded by other factors. To address this challenge, we first utilized multi-omics data from 87 well phenotyped AD patients and generated plasma proteomics and metabolomics data, as well as gut and saliva metagenomics data to investigate the molecular-level alterations accounting the host-microbiome interactions. Second, we analyzed individual omics data and identified the key parameters involved in the severity of the dementia in AD patients. Next, we employed Artificial Intelligence (AI) based models to predict AD severity based on the significantly altered features identified in each omics analysis. Based on our integrative analysis, we found the clinical relevance of plasma proteins, including SKAP1 and NEFL, plasma metabolites including homovanillate and glutamate, and Paraprevotella clara in gut microbiome in predicting the AD severity. Finally, we validated the predictive power of our AI based models by generating additional multi-omics data from the same group of AD patients by following up for 3 months. Hence, we observed that these results may have important implications for the development of potential diagnostic and therapeutic approaches for AD patients., (© 2024. Crown.)

Sarcopenia is a major public health concern among older adults, leading to disabilities, falls, fractures, and mortality. This study aimed to elucidate the pathophysiological mechanisms of sarcopenia and identify potential therapeutic targets using systems biology approaches. RNA-seq data from muscle biopsies of 24 sarcopenic and 29 healthy individuals from a previous cohort were analysed. Differential expression, gene set enrichment, gene co-expression network, and topology analyses were conducted to identify target genes implicated in sarcopenia pathogenesis, resulting in the selection of 6 hub genes (PDHX, AGL, SEMA6C, CASQ1, MYORG, and CCDC69). A drug repurposing approach was then employed to identify new pharmacological treatment options for sarcopenia (clofibric-acid, troglitazone, withaferin-a, palbociclib, MG-132, bortezomib). Finally, validation experiments in muscle cell line (C2C12) revealed MG-132 and troglitazone as promising candidates for sarcopenia treatment. Our approach, based on systems biology and drug repositioning, provides insight into the molecular mechanisms of sarcopenia and offers potential new treatment options using existing drugs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Mitochondrial dysfunction and metabolic abnormalities are acknowledged as significant factors in the onset of neurodegenerative disorders such as Parkinson's disease (PD) and Alzheimer's disease (AD). Our research has demonstrated that the use of combined metabolic activators (CMA) may alleviate metabolic dysfunctions and stimulate mitochondrial metabolism. Therefore, the use of CMA could potentially be an effective therapeutic strategy to slow down or halt the progression of PD and AD. CMAs include substances such as the glutathione precursors (L-serine and N-acetyl cysteine), the NAD+ precursor (nicotinamide riboside), and L-carnitine tartrate., Methods: Here, we tested the effect of two different formulations, including CMA1 (nicotinamide riboside, L-serine, N-acetyl cysteine, L-carnitine tartrate), and CMA2 (nicotinamide, L-serine, N-acetyl cysteine, L-carnitine tartrate), as well as their individual components, on the animal models of AD and PD. We assessed the brain and liver tissues for pathological changes and immunohistochemical markers. Additionally, in the case of PD, we performed behavioral tests and measured responses to apomorphine-induced rotations., Findings: Histological analysis showed that the administration of both CMA1 and CMA2 formulations led to improvements in hyperemia, degeneration, and necrosis in neurons for both AD and PD models. Moreover, the administration of CMA2 showed a superior effect compared to CMA1. This was further corroborated by immunohistochemical data, which indicated a reduction in immunoreactivity in the neurons. Additionally, notable metabolic enhancements in liver tissues were observed using both formulations. In PD rat models, the administration of both formulations positively influenced the behavioral functions of the animals., Interpretation: Our findings suggest that the administration of both CMA1 and CMA2 markedly enhanced metabolic and behavioral outcomes, aligning with neuro-histological observations. These findings underscore the promise of CMA2 administration as an effective therapeutic strategy for enhancing metabolic parameters and cognitive function in AD and PD patients.

Objectives-Aim: We aimed to show the composition and structure of and explore affecting factors on airway microbiota in primary ciliary dyskinesia (PCD) patients using culture-independent techniques., Method: A cross-sectional observational study was performed. We recruited 14 PCD patients (seven pairs of siblings) and nine parents. Bacterial rDNA was extracted from sputum and nasal samples. Sputum samples were also inoculated on suitable bacteriological media., Results: Thirty-three separate genera were detected in sputum samples of PCD patients, and 41 were in nasal samples of parents. The detected genera were dominated by phyla Proteobacteria in PCD patients and their parents. Culture-dependent analyses could not detect many of the bacterial species detected with culture-independent analyses. There were no significant differences in alpha diversity between the siblings' pairs, and siblings' samples did not cluster together nearly as strongly as nonsiblings' samples. Patients who had no new complaints and no bacterial growth with the culture-dependent method at the time of study and patients who had no Haemophilus influenzae growth in the previous year had a significantly greater diversity (p < .05). Microbiota communities tended to cluster together by age, pulmonary exacerbation status, the existence of at least one H. influenzae growth with culture-dependent analyses in the previous year, and forced expiratory volume in 1 sec z and FEF25-75 z-scores., Conclusion: The airway microbiota of patients with PCD have presented more diverse bacterial communities than had been indicated with culture-dependent methods. The study identifies relationships between bacterial airway microbiota composition and the clinical measures of patients. Sibling pairs have no more community similarities than nonsibling PCD patients. Our results may indicate that the patients' clinical characteristics, which determine the disease severity, might affect the PCD microbiome., (© 2023 Wiley Periodicals LLC.)

Background: Transient receptor potential (TRP) channels have been found to have significant implications in neuronal outgrowth, survival, inflammatory neurogenic pain, and various epileptogenic processes. Moreover, there is a growing body of evidence indicating that transient receptor potential (TRP) channels have a significant impact on epilepsy and its drug-resistant subtypes., Objective: We postulated that E Gb 761 would modulate TRPA1 channels, thereby exhibiting anti-inflammatory and neuroprotective effects in a neuroblastoma cell line. Our rationale was to investigate the impact of EGb 761 in a controlled model of pentylenetetrazole-induced generalized epilepsy., Methodology: We evaluated the neuroprotective, antioxidant and anti-apoptotic effects of E Gb 761 both before and after the pentylenetetrazole application in a neuroblastoma cell line. Specifically, we focused on the effects of EGB 761 on the activity of Transient receptor potential (TRP) channels., Results: EGb 761 applications both before and after the pentylenetetrazole incubation period reduced Ca release and restored apoptosis, ROS changes, mitochondrial depolarization and caspase levels, suggesting a prominent prophylactic and therapeutic effect of E Gb 761 in the pentylenetetrazole-induced epileptogenesis process., Conclusion: Our basic mechanistic framework for elucidating the pathophysiological significance of fundamental ion mechanisms in a pentylenetetrazole treated neuroblastoma cell line provided compelling evidence for the favorable efficacy and safety profile of Egb 761 in human-relevant in vitro model of epilepsy. To the best of our knowledge, this is the first study to investigate the combined effects of EGb 761 and pentylenetetrazole on TRP channels and measure their activation level in a relevant model of human epileptic diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ovey, Ozsimsek, Velioglu, Altay, Mardinoglu and Yulug.)

Metaheuristic optimization algorithms manage the search process to explore search domains efficiently and are used efficiently in large-scale, complex problems. Transient Search Algorithm (TSO) is a recently proposed physics-based metaheuristic method inspired by the transient behavior of switched electrical circuits containing storage elements such as inductance and capacitance. TSO is still a new metaheuristic method; it tends to get stuck with local optimal solutions and offers solutions with low precision and a sluggish convergence rate. In order to improve the performance of metaheuristic methods, different approaches can be integrated and methods can be hybridized to achieve faster convergence with high accuracy by balancing the exploitation and exploration stages. Chaotic maps are effectively used to improve the performance of metaheuristic methods by escaping the local optimum and increasing the convergence rate. In this study, chaotic maps are included in the TSO search process to improve performance and accelerate global convergence. In order to prevent the slow convergence rate and the classical TSO algorithm from getting stuck in local solutions, 10 different chaotic maps that generate chaotic values instead of random values in TSO processes are proposed for the first time. Thus, ergodicity and non-repeatability are improved, and convergence speed and accuracy are increased. The performance of Chaotic Transient Search Algorithm (CTSO) in global optimization was investigated using the IEEE Congress on Evolutionary Computation (CEC)'17 benchmarking functions. Its performance in real-world engineering problems was investigated for speed reducer, tension compression spring, welded beam design, pressure vessel, and three-bar truss design problems. In addition, the performance of CTSO as a feature selection method was evaluated on 10 different University of California, Irvine (UCI) standard datasets. The results of the simulation showed that Gaussian and Sinusoidal maps in most of the comparison functions, Sinusoidal map in most of the real-world engineering problems, and finally the generally proposed CTSOs in feature selection outperform standard TSO and other competitive metaheuristic methods. Real application results demonstrate that the suggested approach is more effective than standard TSO., Competing Interests: The authors declare that they have no competing interests., (© 2023 Altay and Varol Altay.)

Objective: The course of the vertebral artery and its relationship to the C 0-1-2 structures render it particularly vulnerable to mechanical trauma. In the present study, we investigated the course of vertebral arteries along the craniovertebral junction (CJ) to cast light on the biomechanical aspects of aneurysm formation, focusing mainly on the relation of the vertebral artery injuries to the CJ bony landmarks. Herein, we report our experience with fourteen cases of craniovertebral junction vertebral artery (CJVA) aneurysms and their presentations, management, and outcomes., Materials and Methods: We extracted from 83 vertebral artery aneurysms only those 14 cases whose aneurysms were located at the C 0-1-2 . We reviewed all medical records, including operative reports and radiologic images. We divided the CJVA into 5 segments and then carefully reviewed the cases, largely focusing on the CJVA segments involved in the aneurysm. Angiographic outcomes were determined by angiography, which was scheduled at 3-6 months, 1, 2.5, and 5 years postoperatively., Results: A total of 14 patients with CJVA aneurysms were included in the present study. 35.7 % had cerebrovascular risk factors, while 23.5 % had other predisposing factors such as an AVM, an AVF, or a foramen magnum tumor. Predisposing factors in the form of neck trauma, both direct and indirect, were identified in 50 % of cases. The segmental distribution of aneurysms was as follows: three (21.4 %) at CJV 1, one (7.1 %) at CJV 2, four (28.6 %) at CJV 3, two (14.3 %) at CJV 4, and four (28.6 %) isolated to the CJV 5 segment. Of the 6 indirect traumatic aneurysms, 1 (16.7 %) was located at CJV 1, 4 (66.7 %) were located at CJV 3 and 1 (16.7 %) was located at CJV 5. The 1/1 direct traumatic aneurysm (100 %) from the penetrating injury was located at CJV 1. 100 % of cases with cerebrovascular risk factors, the affected vessels were on the dominant side. 42.9 % of cases presented symptoms of a vertebrobasilar stroke. All 14 aneurysms were managed only endovascularly. 85.8 % of patients we implemented flow diverters only. 57.1 % of follow-up cases were completely occluded angiographically, and 42.9 % of cases were near-completely or incompletely occluded at 1, 2.5, and 5-year follow-ups., Conclusions: The current article is the first report of a series of vertebral artery aneurysms located in CJ. Herein, the association of vertebral artery aneurysm, hemodynamics, and trauma is well established. We clarified all segments of the CJVA and showed that the segmental distribution of CJVA aneurysms significantly differs between traumatic and spontaneous cases. We showed that treatment with flow diverters should be the mainstay of CJVA aneurysm treatment., Competing Interests: Competing interests The authors declare that they have no competing interests during the writing or submission of this article., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), are associated with metabolic abnormalities. Integrative analysis of human clinical data and animal studies have contributed to a better understanding of the molecular and cellular pathways involved in the progression of NDDs. Previously, we have reported that the combined metabolic activators (CMA), which include the precursors of nicotinamide adenine dinucleotide and glutathione can be utilized to alleviate metabolic disorders by activating mitochondrial metabolism., Methods: We first analysed the brain transcriptomics data from AD patients and controls using a brain-specific genome-scale metabolic model (GEM). Then, we investigated the effect of CMA administration in animal models of AD and PD. We evaluated pathological and immunohistochemical findings of brain and liver tissues. Moreover, PD rats were tested for locomotor activity and apomorphine-induced rotation., Findings: Analysis of transcriptomics data with GEM revealed that mitochondrial dysfunction is involved in the underlying molecular pathways of AD. In animal models of AD and PD, we showed significant damage in the high-fat diet groups' brain and liver tissues compared to the chow diet. The histological analyses revealed that hyperemia, degeneration and necrosis in neurons were improved by CMA administration in both AD and PD animal models. These findings were supported by immunohistochemical evidence of decreased immunoreactivity in neurons. In parallel to the improvement in the brain, we also observed dramatic metabolic improvement in the liver tissue. CMA administration also showed a beneficial effect on behavioural functions in PD rats., Interpretation: Overall, we showed that CMA administration significantly improved behavioural scores in parallel with the neurohistological outcomes in the AD and PD animal models and is a promising treatment for improving the metabolic parameters and brain functions in NDDs., Competing Interests: Declaration of competing interest AM, JB and MU are the founder and shareholders of ScandiBio Therapeutics. The other authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Alzheimer's disease (AD) is associated with metabolic abnormalities linked to critical elements of neurodegeneration. We recently administered combined metabolic activators (CMA) to the AD rat model and observed that CMA improves the AD-associated histological parameters in the animals. CMA promotes mitochondrial fatty acid uptake from the cytosol, facilitates fatty acid oxidation in the mitochondria, and alleviates oxidative stress., Methods: Here, we designed a randomised, double-blinded, placebo-controlled phase-II clinical trial and studied the effect of CMA administration on the global metabolism of AD patients. One-dose CMA included 12.35 g L-serine (61.75%), 1 g nicotinamide riboside (5%), 2.55 g N-acetyl-L-cysteine (12.75%), and 3.73 g L-carnitine tartrate (18.65%). AD patients received one dose of CMA or placebo daily during the first 28 days and twice daily between day 28 and day 84. The primary endpoint was the difference in the cognitive function and daily living activity scores between the placebo and the treatment arms. The secondary aim of this study was to evaluate the safety and tolerability of CMA. A comprehensive plasma metabolome and proteome analysis was also performed to evaluate the efficacy of the CMA in AD patients., Results: We showed a significant decrease of AD Assessment Scale-cognitive subscale (ADAS-Cog) score on day 84 vs day 0 (P = 0.00001, 29% improvement) in the CMA group. Moreover, there was a significant decline (P = 0.0073) in ADAS-Cog scores (improvement of cognitive functions) in the CMA compared to the placebo group in patients with higher ADAS-Cog scores. Improved cognitive functions in AD patients were supported by the relevant alterations in the hippocampal volumes and cortical thickness based on imaging analysis. Moreover, the plasma levels of proteins and metabolites associated with NAD + and glutathione metabolism were significantly improved after CMA treatment., Conclusion: Our results indicate that treatment of AD patients with CMA can lead to enhanced cognitive functions and improved clinical parameters associated with phenomics, metabolomics, proteomics and imaging analysis. Trial registration ClinicalTrials.gov NCT04044131 Registered 17 July 2019, https://clinicaltrials.gov/ct2/show/NCT04044131., (© 2023. The Author(s).)

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a complex disease involving alterations in multiple biological processes regulated by the interactions between obesity, genetic background, and environmental factors including the microbiome. To decipher hepatic steatosis (HS) pathogenesis by excluding critical confounding factors including genetic variants and diabetes, 56 heterogenous MAFLD patients are characterized by generating multiomics data including oral and gut metagenomics as well as plasma metabolomics and inflammatory proteomics data. The dysbiosis in the oral and gut microbiome is explored and the host-microbiome interactions based on global metabolic and inflammatory processes are revealed. These multiomics data are integrated using the biological network and HS's key features are identified using multiomics data. HS is finally predicted using these key features and findings are validated in a follow-up cohort, where 22 subjects with varying degree of HS are characterized., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Metal levels and potential health risk assessment in muscle, liver, and gills of three fish species (Merluccius merluccius, Mullus barbatus, and Pagellus erythrinus) from the Edremit Bay were investigated in spring and autumn 2015. Metal concentrations (Hg, Cd, Pb, Cr, Cu, Zn, Mn, and Fe), metal pollution index, and bioaccumulation factors in P. erythrinus were observed to be generally higher than those in M. barbatus and M. merluccius. Tissue was the main factor that might be responsible from the variations of metals in fish species according to ANOVA and PCA. Hg concentrations in M. barbatus and P. erythrinus were greater than threshold limits defined by international authorities; however, no carcinogenic risks were found for Cd and Pb levels. According to the results, the bay has been negatively influenced by human activities, and further research on monitoring of the biota and sediments is recommended for Edremit Bay and similar coastal areas under human pressure., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The use of anticancer peptides (ACPs) as an alternative/complementary strategy to conventional chemotherapy treatments has been shown to decrease drug resistance and/or severe side effects. However, the efficacy of the positively-charged ACP is inhibited by elevated levels of negatively-charged cell-surface components which trap the peptides and prevent their contact with the cell membrane. Consequently, this decreases ACP-mediated membrane pore formation and cell lysis. Negatively-charged heparan sulphate (HS) and chondroitin sulphate (CS) have been shown to inhibit the cytotoxic effect of ACPs. In this study, we propose a strategy to promote the broad utilization of ACPs. In this context, we developed a drug repositioning pipeline to analyse transcriptomics data generated for four different cancer cell lines (A549, HEPG2, HT29, and MCF7) treated with hundreds of drugs in the LINCS L1000 project. Based on previous studies identifying genes modulating levels of the glycosaminoglycans (GAGs) HS and CS at the cell surface, our analysis aimed at identifying drugs inhibiting genes correlated with high HS and CS levels. As a result, we identified six chemicals as likely repositionable drugs with the potential to enhance the performance of ACPs. The codes in R and Python programming languages are publicly available in https://github.com/ElyasMo/ACPs&#95;HS&#95;HSPGs&#95;CS. As a conclusion, these six drugs are highlighted as excellent targets for synergistic studies with ACPs aimed at lowering the costs associated with ACP-treatment., (© 2021 Wiley-VCH GmbH.)

Superelastic shape memory alloy (SMA) wires exhibit superb hysteretic energy dissipation and deformation capabilities. Therefore, they are increasingly used for the vibration control of civil engineering structures. The efficient design of SMA-based control devices requires accurate material models. However, the thermodynamically coupled SMA behavior is highly sensitive to strain rate. For an accurate modelling of the material behavior, a wide range of parameters needs to be determined by experiments, where the identification of thermodynamic parameters is particularly challenging due to required technical instruments and expert knowledge. For an efficient identification of thermodynamic parameters, this study proposes a machine-learning-based approach, which was specifically designed considering the dynamic SMA behavior. For this purpose, a feedforward artificial neural network (ANN) architecture was developed. For the generation of training data, a macroscopic constitutive SMA model was adapted considering strain rate effects. After training, the ANN can identify the searched model parameters from cyclic tensile stress-strain tests. The proposed approach is applied on superelastic SMA wires and validated by experiments.

Glioblastoma multiforme (GBM) is one of the most malignant central nervous system tumors, showing a poor prognosis and low survival rate. Therefore, deciphering the underlying molecular mechanisms involved in the progression of the GBM and identifying the key driver genes responsible for the disease progression is crucial for discovering potential diagnostic markers and therapeutic targets. In this context, access to various biological data, development of new methodologies, and generation of biological networks for the integration of multi-omics data are necessary for gaining insights into the appearance and progression of GBM. Systems biology approaches have become indispensable in analyzing heterogeneous high-throughput omics data, extracting essential information, and generating new hypotheses from biomedical data. This review provides current knowledge regarding GBM and discusses the multi-omics data and recent systems analysis in GBM to identify key biological functions and genes. This knowledge can be used to develop efficient diagnostic and treatment strategies and can also be used to achieve personalized medicine for GBM.

Background: COVID-19 has caused millions of deaths globally, yet the cellular mechanisms underlying the various effects of the disease remain poorly understood. Recently, a new analytical platform for comprehensive analysis of plasma protein profiles using proximity extension assays combined with next generation sequencing has been developed, which allows for multiple proteins to be analyzed simultaneously without sacrifice on accuracy or sensitivity., Methods: We analyzed the plasma protein profiles of COVID-19 patients (n = 50) with mild and moderate symptoms by comparing the protein levels in newly diagnosed patients with the protein levels in the same individuals after 14 days., Findings: The study has identified more than 200 proteins that are significantly elevated during infection and many of these are related to cytokine response and other immune-related functions. In addition, several other proteins are shown to be elevated, including SCARB2, a host cell receptor protein involved in virus entry. A comparison with the plasma protein response in patients with severe symptoms shows a highly similar pattern, but with some interesting differences., Interpretation: The study presented here demonstrates the usefulness of "next generation plasma protein profiling" to identify molecular signatures of importance for disease progression and to allow monitoring of disease during recovery from the infection. The results will facilitate further studies to understand the molecular mechanism of the immune-related response of the SARS-CoV-2 virus., Funding: This work was financially supported by Knut and Alice Wallenberg Foundation., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Blood-brain barrier (BBB) disruption is a common and critical pathology following subarachnoid hemorrhage (SAH). We investigated the BBB disruption property of secreted protein acidic and rich in cysteine (SPARC) after SAH. A total of 197 rats underwent endovascular perforation to induce SAH or sham operation. Small interfering ribonucleic acid (siRNA) for SPARC or scrambled siRNA was administered intracerebroventricularly to rats 48 h before SAH. Anti-SPARC monoclonal antibody (mAb) 236 for functional blocking or normal mouse immunoglobulin G (IgG) was administered intracerebroventricularly 1 h after SAH. Selective integrin α V β 3 inhibitor cyclo(-RGDfK) or phosphate-buffered saline was administered intranasally 1 h before SAH, along with recombinant SPARC treatment. Neurobehavior, SAH severity, brain edema, immunohistochemical staining, and Western blot were evaluated. The expression of SPARC and integrin α V β 3 was upregulated after SAH in the endothelial cells. SPARC siRNA and anti-SPARC mAb 236 prevented neuroimpairments and brain edema through protection of BBB as measured by IgG extravasation 24 and 72 h after SAH. Recombinant SPARC aggravated neuroimpairments and cyclo(-RGDfK) suppressed the harmful neurological effects via inhibition of activated c-Jun N-terminal kinase, p38, and matrix metalloproteinase-9 followed by retention of endothelial junction proteins. SPARC may induce post-SAH BBB disruption via integrin α V β 3 signaling pathway., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Takeshi Okada et al.)

Two reversed-phase HPLC methods for molecular analysis of dissolved free monosaccharides in seawater were investigated comparatively by optimizing chromatographic separations and pre-column derivatization reactions. Monosaccharides derivatized with 2-amino benzamide or 2-amino pyrazine, and reduced with 2-picoline borane or 2-dimethylamino borane. According to results of optimization, separation performance, and detection limits, 2-amino benzamide method gave better results than 2-amino pyrazine method. Among 12 monosaccharides tested, it was possible to quantify glucose + galactose, galacturonic acid, glucuronic acid, xylose + arabinose, ribose, mannose, and N-acetyl-d-glucosamine with detection limits between 1.2 and 11 nM with intra-day repeatability of 2-9% and inter-day repeatability of 3-9%. The optimized method has the same level of detection limit with a widely used anion exchange chromatography method. Besides the preliminary results reported in this study, it may be possible to achieve higher sensitivity and to detect more monosaccharides by the use of shorter and narrow-bore columns at different polarities in further studies., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The complex pathology of Alzheimer's disease (AD) emphasises the need for comprehensive modelling of the disease, which may lead to the development of efficient treatment strategies. To address this challenge, we analysed transcriptome data of post-mortem human brain samples of healthy elders and individuals with late-onset AD from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP) and Mayo Clinic (MayoRNAseq) studies in the AMP-AD consortium. In this context, we conducted several bioinformatics and systems medicine analyses including the construction of AD-specific co-expression networks and genome-scale metabolic modelling of the brain in AD patients to identify key genes, metabolites and pathways involved in the progression of AD. We identified AMIGO1 and GRPRASP2 as examples of commonly altered marker genes in AD patients. Moreover, we found alterations in energy metabolism, represented by reduced oxidative phosphorylation and ATPase activity, as well as the depletion of hexanoyl-CoA, pentanoyl-CoA, (2E)-hexenoyl-CoA and numerous other unsaturated fatty acids in the brain. We also observed that neuroprotective metabolites (e.g., vitamins, retinoids and unsaturated fatty acids) tend to be depleted in the AD brain, while neurotoxic metabolites (e.g., β-alanine, bilirubin) were more abundant. In summary, we systematically revealed the key genes and pathways related to the progression of AD, gained insight into the crucial mechanisms of AD and identified some possible targets that could be used in the treatment of AD.