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Testing for genetic alterations in tumor tissue allows clinicians to identify patients who most likely will benefit from molecular targeted treatment. EXLIQUID – exploiting liquid biopsies to advance cancer precision medicine – investigates the potential of additional non-invasive tools for guiding therapy decisions and monitoring of advanced cancer patients. The term “liquid biopsy” (LB) refers to non-invasive analysis of tumor-derived circulating material such as cell-free DNA in blood samples from cancer patients. Although recent technological advances allow sensitive and specific detection of LB biomarkers, only few LB assays have entered clinical routine to date. EXLIQUID is a German Cancer Consortium (DKTK)-wide joint funding project that aims at establishing LBs as a minimally-invasive tool to analyze molecular changes in circulating tumor DNA (ctDNA). Here, we present the structure, clinical aim, and methodical approach of the new DKTK EXLIQUID consortium. Within EXLIQUID, we will set up a multicenter repository of high-quality LB samples from patients participating in DKTK MASTER and local molecular tumor boards, which use molecular profiles of tumor tissues to guide targeted therapies. We will develop LB assays for monitoring of therapy efficacy by the analysis of tumor mutant variants and tumor-specific DNA methylation patterns in ctDNA from these patients. By bringing together LB experts from all DKTK partner sites and exploiting the diversity of their particular expertise, complementary skills and technologies, the EXLIQUID consortium addresses the challenges of translating LBs into the clinic. The DKTK structure provides EXLIQUID a unique position for the identification of liquid biomarkers even in less common tumor types, thereby extending the group of patients benefitting from non-invasive LB testing. Besides its scientific aims, EXLIQUID is building a valuable precision oncology cohort and LB platform which will be available for future collaborative research studies within the DKTK and beyond.

The dynamic economic load dispatch problem (DELDP), with the consideration of valve-point effects, is a complicated non-linear constrained optimization problem with nonsmooth and non-convex characteristics. The main goal of DELDP is to find out the optimal generation schedule of the generators corresponding to the most economical operating point of the system over the considered timing horizon. In this paper, a new swarm based optimization algorithm, so called gravitational search algorithm (GSA) has been proposed to solve the DELDP with considering valve-point effects and transmission power loss constraints. The performance of the proposed method is rigorously tested for optimality, convergence, robustness and computational efficiency on a 10-unit test system with a 24-h load demand at each 1-h time intervals which is so well-known and common in literature. The proposed algorithm also takes care of different constraints like power balance, ramp rate limits and generation limits. The simulation results reveal that, compared with other methods reported in literatures recently, the proposed GSA method are capable of obtaining better quality solutions with higher efficiency. In addition, sensitivity analysis has been performed on the controlling parameters of GSA to reach the best arrangement for them. [ABSTRACT FROM AUTHOR]

Investments made in the energy sector have a strong influence on the degree of dependence between economies, their competitiveness, sustainability, and on all sorts of environmental aspects including climate change. Recently, using renewable energy sources as distributed generation systems are expanding through the world. In this paper, a photovoltaicwind generator system is designed as a distributed generation system to supply a typical scheduled load. The goal of mentioned design is to minimize the total cost of the system in a 20- year round, during its life time. A new optimization algorithm based on swarm-based intelligence which is called gravitational search algorithm (GSA) has been applied to optimize the total cost. Finally, by using data of wind speed and irradiance of a province in north of Iran, which is called Ardebil, the model was simulated for the province and then, optimization process was implemented using the proposed algorithm. Simulation results show that using renewable energy sources as distributed generation systems for small consumers are economically profitable. [ABSTRACT FROM AUTHOR]

Based on definition of angular central moments, a quantitative measure is proposed for comparative assessment of the anisotropy of different intermolecular potential energy surfaces at different intermolecular distances. Angular spreadness, skewness and peakedness are three features of anisotropy that are used here to describe the distribution of values of interaction energy around its isotropic component. In agreement with qualitative interpretations, the proposed measure exhibits a sharp change in the R-dependent pattern of anisotropy at an intermediate distance where the repulsive forces on the average overcome the attractive ones. The R-dependence of anisotropy of available N2–N2potentials is examined in comparison with bare ab initiodata and considerable discrepancies are found at distances shorter than the onset of repulsion. It is shown that the full experimentally derived potentials with simplified functional forms do not reproduce the correct anisotropy of interaction energy. [ABSTRACT FROM AUTHOR]

A series of high temperature and organosoluble poly(amide-imide)s 8a–g were prepared by direct polycondensation from 1,4-bis[4-aminophenoxy]butane 4 and various aromatic diacids 7a–g in a medium consisting of N-methyl-2-pyrrolidone (NMP)/triphenyl phosphite (TPP)/calcium chloride (CaCl2)/pyridine system. Aromatic diacids 7a–g were synthesized by reaction of 3,3′,4,4′-benzophenone tetra carboxylic dianhydride 5 and various amino acids 6a–g. All of the above polymers were fully characterized by 1H-NMR and FT-IR spectroscopy, inherent viscosity, solubility test and thermogravimetric analysis (TGA). The resulted polyamides (PAs) 8a–g have showed admirable good inherent viscosities, thermal stability and solubility.

Background: A connection has been established between ocular structural changes and various neurodegenerative diseases. Several studies utilizing optical coherence tomography (OCT) have detected signs of ocular structural alterations among individuals with Huntington's disease (HD). The inconsistent results reported in the literature regarding alterations in the retina and choroid encouraged us to conduct this systematic review and meta-analysis to accumulate the findings., Methods: A systematic search was carried out in three electronic databases (PubMed, Embase, Scopus) to find studies reporting OCT measurements in HD cases compared with healthy controls (HC). A fixed-effects or random-effects meta-analysis was conducted according to the detected heterogeneity level. Furthermore, subgroup and sensitivity analyses, meta-regression, and quality assessment were performed., Results: Eleven studies were included in the systematic review and 9 studies with a total population of 452 participants (241 cases, and 211 HC) underwent meta-analysis. Results of the analysis denoted that subfoveal choroid had a significantly reduced thickness in HD eyes compared to HC (p < 0.0001). Moreover, our analysis indicated that HD cases had a significantly thinner average (p = 0.0130) and temporal peripapillary retinal nerve fiber layer (pRNFL) (p = 0.0012) than HC. However, subjects with pre-HD had insignificant differences in average (p = 0.44) and temporal pRNFL thickness (p = 0.33) with the HC group., Conclusion: Results of the current systematic review and meta-analysis revealed the significant thinning of average and temporal pRNFL and subfoveal choroid in HD compared to HC. However, OCT currently might be considered insensitive to be applied in the pre-HD population at least until further longitudinal investigations considering variables such as the duration between OCT measurement and disease onset validating OCT as a routine diagnostic tool in HD clinics., (© 2024. The Author(s).)

Background: Impaired immune response in multiple myeloma renders the patients vulnerable to infections, such as COVID-19, and may cause worse response to vaccines. Researchers should analyze this issue to enable the planning for special preventive measures, such as increased booster doses. Therefore, this meta-analysis aimed to evaluate the response and efficacy of COVID-19 vaccines in patients with multiple myeloma., Methods: This meta-analysis followed PRISMA 2020 guidelines, conducting a comprehensive database search using specified keywords. Study selection involved a two-phase title/abstract and full-text screening process. Data extraction was performed by two researchers, and statistical analysis involved meta-analysis, subgroup analysis based on vaccine dosage and study time, random effects meta-regression, and heterogeneity testing using the Q test., Results: The meta-analysis revealed that patients with multiple myeloma (MM) had a lower likelihood of developing detectable antibodies after COVID-19 vaccination compared to healthy controls (Log odds ratio with 95% CI: -3.34 [-4.08, -2.60]). The analysis of antibody response after different doses showed consistent lower seropositivity in MM patients (after first dose: -2.09, [-3.49, -0.69], second: -3.80, 95%CI [-4.71, -3.01], a booster dose: -3.03, [-5.91, -0.15]). However, there was no significant difference in the mean level of anti-S antibodies between MM patients and controls (Cohen's d -0.72, [-1.86, 0.43]). Evaluation of T-cell responses indicated diminished T-cell-mediated immunity in MM patients compared to controls. Seven studies reported clinical response, with breakthrough infections observed in vaccinated MM patients., Conclusions: These findings highlight the impaired humoral and cellular immune responses in MM patients after COVID-19 vaccination, suggesting the need for further investigation and potential interventions., (© 2024. The Author(s).)

The intrinsic mechanisms that regulate neurotoxic versus neuroprotective astrocyte phenotypes and their effects on central nervous system degeneration and repair remain poorly understood. Here we show that injured white matter astrocytes differentiate into two distinct C3-positive and C3-negative reactive populations, previously simplified as neurotoxic (A1) and neuroprotective (A2) 1,2 , which can be further subdivided into unique subpopulations defined by proliferation and differential gene expression signatures. We find the balance of neurotoxic versus neuroprotective astrocytes is regulated by discrete pools of compartmented cyclic adenosine monophosphate derived from soluble adenylyl cyclase and show that proliferating neuroprotective astrocytes inhibit microglial activation and downstream neurotoxic astrocyte differentiation to promote retinal ganglion cell survival. Finally, we report a new, therapeutically tractable viral vector to specifically target optic nerve head astrocytes and show that raising nuclear or depleting cytoplasmic cyclic AMP in reactive astrocytes inhibits deleterious microglial or macrophage cell activation and promotes retinal ganglion cell survival after optic nerve injury. Thus, soluble adenylyl cyclase and compartmented, nuclear- and cytoplasmic-localized cyclic adenosine monophosphate in reactive astrocytes act as a molecular switch for neuroprotective astrocyte reactivity that can be targeted to inhibit microglial activation and neurotoxic astrocyte differentiation to therapeutic effect. These data expand on and define new reactive astrocyte subtypes and represent a step towards the development of gliotherapeutics for the treatment of glaucoma and other optic neuropathies., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Although several studies have shown that the Coronavirus Disease 2019 (COVID-19) lockdown has had negative impacts on mental health and eating behaviors among the general population and athletes, few studies have examined the long-term effects on elite and sub-elite athletes. The present study aimed to investigate the long-term impact of COVID-19 lockdown on mental health and eating behaviors in elite versus sub-elite athletes two years into the pandemic. A cross-sectional comparative study was conducted between March and April 2022, involving athletes from 14 countries, using a convenient non-probabilistic and snowball sampling method. A total of 1420 athletes (24.5 ± 7.9 years old, 569 elites, 35% women, and 851 sub-elites, 45% women) completed an online survey-based questionnaire. The questionnaire included a sociodemographic survey, information about the COVID-19 pandemic, the Depression, Anxiety and Stress Scale-21 Items (DASS-21) for mental health assessment, and the Rapid Eating Assessment for Participants (REAP-S) for assessing eating behavior., Results: The results showed that compared to sub-elite athletes, elite athletes had lower scores on the DASS-21 (p = .001) and its subscales of depression (p = .003), anxiety (p = .007), and stress (p < .001), as well as a lower REAP-S score indicating lower diet quality (p = .013)., Conclusion: In conclusion, two years into the pandemic, elite athletes were likelier to have better mental health profiles than sub-elite athletes but surprisingly had lower diet quality., (© 2023. The Author(s).)

Background: Although the gastrointestinal tract is one of the most common sites for extranodal lymphoma, gastrointestinal lymphoma is a rare disease that is almost exclusively non-Hodgkin lymphoma., Case Presentation: We present a rare condition of Hodgkin lymphoma relapse after 12 years as isolated gastric involvement caused massive gastrointestinal bleeding in a 34-year-old Iranian woman. According to the result of the upper endoscopy, laparotomy was performed, and a large mass in the upper part of the fundus, alongside the esophagogastric junction, was seen, so gastrectomy was performed., Conclusion: All symptoms and paraclinical findings for gastrointestinal Hodgkin lymphoma are nonspecific. Therefore, the preoperative diagnosis is challenging. It seems that surgery is a suitable diagnostic and therapeutic method in this field., (© 2023. The Author(s).)

The assembly of the amyloid- β peptide (A β ) into toxic oligomers and fibrils is associated with Alzheimer's disease and dementia. Therefore, disrupting amyloid assembly by direct targeting of the A β monomeric form with small molecules or antibodies is a promising therapeutic strategy. However, given the dynamic nature of A β , standard computational tools cannot be easily applied for high-throughput structure-based virtual screening in drug discovery projects. In the current study, we propose a computational pipeline-in the framework of the ensemble docking strategy-to identify catechins' binding sites in monomeric A β 42 . It is shown that both hydrophobic aromatic interactions and hydrogen bonding are crucial for the binding of catechins to A β 42 . Additionally, it has been found that all the studied ligands, especially EGCG , can act as potent inhibitors against amyloid aggregation by blocking the central hydrophobic region of A β . Our findings are evaluated and confirmed with multi-microsecond MD simulations. Finally, it is suggested that our proposed pipeline, with low computational cost in comparison with MD simulations, is a suitable approach for the virtual screening of ligand libraries against A β .

Objectives: Recent investigations indicate that canine periodontal ligament-derived stem cells (cPDLSCs) may reveal a reliable strategy for repair of periodontal tissues via cell-based tissue engineering approaches . Due to limited research, t his study aimed to demonstrate the phenotypic characterization of cPDLSc in comparison with canine bone marrow-derived mesenchymal stem cells (cBMSCs) in vitro., Methods: Mesenchymal stem cells (MSCs) were obtained from PDL and BM of five male adult Mongrel dogs. In vitro isolation and expansion as well as biologic characterization including colony unit formation (CFU), osteogenic and adipogenic differentiation, flow cytometric analysis of CD34 and CD44, and RT-PCR of alkaline phosphatase (ALP), osteocalcin (OCN), periostin (POSTN) and S100A4 were performed. Furthermore, electron microscopy analysis was done to complement the comparative research., Results: CFU assay revealed that colonies of cPDLSCs presented 70% confluency with a more finite lifespan than BM-MSCs, showing a significant increase in cPDLSCs. Both types of MSCs showed osteogenic and adipogenic phenotypic characterized with clusters of mineralized depositions and lipid vacuoles, respectively. Both types of MSCs expressed CD44 with limited expression of CD34. RT-PCR of cPDLSCs revealed that expression of ALP, POSTN, OCN and S100A4 genes were significantly higher than those of BMSCs. In addition, comparison of SEM and revealed that cPDLSCs expressed more extracellular collagen fibers., Conclusions: The current study indicated that cPDLSCs show potency as a novel cellular therapy for periodontal regeneration a large animal model., Competing Interests: Authors declare no conflict of interest., (© 2023 Published by Elsevier B.V. on behalf of Craniofacial Research Foundation.)

Analytical models and the prediction of accidents and their consequences are important tools for preventing accidents in the industry. Therefore, the present study was conducted to review process accident consequence modeling in Iran (2006-2022), helping improve incident modeling, and creating a context for preventing these accidents. In this study, the articles of 5 international Embase Medline/PubMed databases, ProQuest, Scopus, Google Scholar, and Web of Science, and four Iranian databases SID, MagIran, IranMedex, and IranDoc were examined using the PRISMA checklist. After reviewing the studies, 40 articles were included in the final analysis. The results showed that 25 studies used PHAST software, 11 studies used ALOHA software and 4 studies used ALOHA and PHAST software together. The highest number of studies was conducted in Imam Khomeini Port and Asaluyeh city, respectively. In addition, the number of studies published in Persian was more than in other studies. There was no similar agreement between the results of the two software in providing correct results at low concentrations. PHAST software also provided more accurate results than ALOHA over longer distances in stable and relatively stable weather conditions. The study and identification of hazards and scenarios in the studies that used PHAST software were more, more accurate and more coherent than in the studies that used ALOHA software. It is suggested that in future studies the same scenario can be compared with PHAST, ALOHA, and newer modeling software such as Fire Dynamics Simulator (FDS)., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Published by Elsevier Ltd.)