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Manal S Ebaid,1,2 Maciej Chyb,3,4 Veronika Furlan,5 Hoda Atef Abdelsattar Ibrahim,6 Urban Bren,5,7,8 Justyna Gatkowska,3 Jarosław Dziadek,9 Wagdy M Eldehna,10,11 Ahmed Sabt2 1Department of Chemistry, College of Science, Northern Border University, Arar, Saudi Arabia; 2Chemistry of Natural Compounds Department, Pharmaceutical and Drug Industries Research Institute, National Research Center, Dokki, Cairo, Egypt; 3Department of Molecular Microbiology, Faculty of Biology and Environmental Protection, University of Lodz, Łódź, Poland; 4Bio-Med-Chem Doctoral School of the University of Lodz and Lodz Institutes of the Polish Academy of Sciences, Łódź, Poland; 5Faculty of Chemistry and Chemical Engineering, University of Maribor, Maribor, Slovenia; 6Pediatric Department, Faculty of Medicine, Cairo University, Cairo, Egypt; 7Faculty of Mathematics, Natural Sciences and Information Technologies, University of Primorska, Glagoljaška 8, Slovenia; 8Institute of Environmental Protection and Sensors, Beloruska Ulica 7, Maribor, Slovenia; 9Laboratory of Genetics and Physiology of Mycobacterium, Institute of Medical Biology of the Polish Academy of Sciences, Łódź, Poland; 10Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egypt; 11Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, EgyptCorrespondence: Ahmed Sabt; Wagdy M Eldehna, Email sabt.nrc@gmail.com; wagdy2000@gmail.comIntroduction: Toxoplasmosis, a zoonotic infection caused by the apicomplexan parasite Toxoplasma gondii, affects a significant portion of the global human population. This condition, particularly dangerous for pregnant women and immunocompromised individuals, currently lacks effective treatment options.Methods: Eighteen coumarin-based derivatives were synthesized, comprising coumarin-chalcone hybrids (5a-i) and coumarin-pyrazoline hybrids (6a-i). Cytotoxicity was evaluated using L929 mouse fibroblasts and Hs27 human fibroblasts. Anti-T. gondii activity was assessed, and molecular docking studies were performed to predict binding modes with TgCDPK1.Results: Pyrazoline hybrids (6a-i) showed lower toxicity than chalcone-bearing coumarins (5a-i), with CC30 values exceeding the highest tested concentration (500 μg/mL) for most compounds. The synthesized molecules demonstrated strong anti-T. gondii activity, with IC50 values ranging from 0.66 μg/mL to 9.05 μg/mL. Molecular docking studies provided insights into potential binding mechanisms.Conclusion: This study highlights the potential of coumarin-based hybrids as anti-T. gondii agents. The findings should contribute to the growing arsenal of small molecules against T. gondii and underscore the value of molecular hybridization in drug design. Further studies to elucidate these compounds’ mechanism of action and in vivo efficacy are warranted to fully realize their potential as anti-parasitic agents.Keywords: Coumarin sulfonamides, Synthesis, N-acetylpyrazoline, TgCDPK1 enzyme, molecular docking

Abstract Background Cancer navigation programs aim to support, educate, and empower patients and families, addressing barriers to diagnostics, treatment, and care. Navigators engage with people to ensure timely access to services and resources. While promising for older people with cancer, these programs are scarce in Europe, and research on their effectiveness and implementation is limited. We describe the protocol of the EU NAVIGATE randomized controlled trial, aimed to evaluate (1) effectiveness and cost-effectiveness of NavCare-EU, an intervention that aims to support older people with cancer throughout their illness trajectory, spanning the continuum of supportive, palliative, and end-of-life care, and (2) the intervention’s implementation processes and feasibility of its integration into different health care systems in Europe, contextual barriers and facilitators for effective and sustainable implementation, and mechanisms involved in reaching the outcomes. Methods We will conduct a multisite pragmatic fast-track randomized controlled trial with embedded convergent mixed-method process evaluation in Belgium, Ireland, Italy, Netherlands, Poland, and Portugal. The study targets people with cancer and declining health, 70 years or older, and their close family caregivers. The trial compares the NavCare-EU intervention plus standard care with standard care alone. We will perform a baseline measurement prior to randomization and follow-up measurements at 12 weeks, 24 weeks, and 48 weeks in intervention and control group, and an additional measurement at 72 weeks in the control group. Primary outcomes, measured at 24 weeks are (1) the older person’s global health status/quality of life, a 2-item subscale from EORTC-QLQ-C30 (revised) measuring health-related quality of life, (2) level of social support measured with Medical Outcomes Study Social Support Survey (MOS-SSS scale). The study will include at least 246 older persons with completed global health status/quality of life at 24 weeks. Discussion The EU NAVIGATE trial will cross-nationally test the effectiveness and cost-effectiveness of a navigation intervention for older people with cancer and their family caregivers, and its implementation in different health care systems in Europe. As continuity and access to health, social, and community care is a priority for patients and caregivers, the trial is timely and critically needed. Trial registration Clinicaltrials.gov: identifier NCT06110312 (2023/10/31).

Abstract We investigated the long-term effects of prenatal nutrition on pre-slaughter Nelore bulls using integrative transcriptome and metabolome analyses of liver tissue. Three prenatal nutritional treatments were administered to 126 cows: NP (control, mineral supplementation only), PP (protein-energy supplementation in the third trimester), and FP (protein-energy supplementation throughout pregnancy). Liver samples from 22.5 ± 1-month-old bulls underwent RNA-Seq and targeted metabolomics. Weighted correlation network analysis (WGCNA) identified treatment-associated gene and metabolite co-expression modules, further analyzed using MetaboAnalyst 6.0 (metabolite over-representation analysis and transcriptome-metabolome integrative analysis) and Enrichr (gene over-representation analysis). We identified several significant gene and metabolite modules, as well as hub components associated with energy, protein and oxidative metabolism, regulatory mechanisms, epigenetics, and immune function. The NP transcriptome-metabolome analysis identified key pathways (aminoacyl t-RNA biosynthesis, gluconeogenesis, and PPAR signaling) and hub components (glutamic acid, SLC6A14). PP highlighted pathways (arginine and proline metabolism, TGF-beta signaling, glyoxylate and dicarboxylate metabolism) with arginine and ODC1 as hub components. This study highlights the significant impact of prenatal nutrition on the liver tissue of Nelore bulls, shedding light on critical metabolic pathways and hub components related to energy and protein metabolism, as well as immune system and epigenetics.

Abstract In this work, we design and implement a new bifocal diffractive spiral lens within an optical tweezers system. The proposed diffractive optical element coined Kolokaski Kinoform Spiral Lens (KKSL), generates twin optical vortices along the propagation direction. The axial positions, as well as the diameters of the generated vortex beams, are correlated with the Kolakoski aperiodic sequence introduced in the design of the diffractive lens. The unique properties of KKSLs make it ideal for optical trapping applications, allowing independent multiple trapping and particle displacement within each optical vortex beam. We present both the focusing properties of KKSL and the experimental results of its integration into the optical tweezer setup.

Abstract Cognitive impairment and symptoms of psychiatric disorders have been reported frequently as features of post-acute sequelae of SARS-CoV-2 infection. This study aims to investigate subjective memory complaints in COVID-19 survivors and determine if these are more strongly associated with objective cognitive impairment related to sequelae of SARS-CoV-2 infection or with symptoms of psychiatric conditions. A total of 608 COVID-19 survivors were evaluated in-person 6–11 months after hospitalization, with 377 patients assigned to a “no subjective memory complaint (SMC)” group and 231 patients assigned to an SMC group based on their Memory Complaint Scale scores. Follow-up evaluations included an objective cognitive battery and scale-based assessments of anxiety, depression, and post-traumatic stress symptoms. We found the perception of memory impairment in COVID-19 survivors to be more strongly associated to core symptoms of psychiatric conditions rather than to primary objective cognitive impairment. Univariate analysis indicated significant differences between the “no SMC” and SMC groups, both for the psychiatric symptom evaluations and for the cognitive evaluations (p

It is widely known that test anxiety (TA) is associated with a decrease in test scores. The objective of this study is to provide evidence of the existence of two paths through which TA affects test scores: an indirect path that is associated with the mediation of the updating efficiency and a direct path moderated by the putting into perspective coping strategy. The study was conducted with a sample of 184 high school students who took an entrance exam for a university in Costa Rica. The structural equation modelling related to the theoretical approach was well adjusted, which provided evidence in favour of the hypotheses about the previously mentioned paths. Based on the results, the use of the putting into perspective coping strategy can help people with high TA levels reduce the effect of this emotion in test scores.

Abstract In the last two decades, an exponentially growing number of meta-analyses (MAs) synthesize thousands of peer-reviewed studies on the environmental impacts of farming practices (FPs). This paper describes the iMAP-FP evidence library, a comprehensive dataset on the effects of 34 categories of FPs (such as agronomic practices, cropping and livestock systems, land management options and mitigation techniques) on 34 impacts including climate mitigation, soil health, environmental pollution, water use, nutrients cycling, biodiversity, and agricultural productivity. Through systematic screening, 570 MAs published since 2000 were selected and categorized according to the type of FP. We assessed their impacts, the geographic regions covered, and their quality. We extracted 3,811 effects and their statistical significance associated with sustainable FPs (intervention) compared to a control (typically conventional agriculture) across 223 different intervention-control pairs. Our dataset is accompanied with an online free-access library, which includes a catalogue of synthetic reports summarizing the available evidence on each evaluated FP.

Abstract The coordinated action of transcriptional and post-transcriptional machineries shapes gene expression programs at steady state and determines their concerted response to perturbations. We have developed Nanodynamo, an experimental and computational workflow for quantifying the kinetic rates of nuclear and cytoplasmic steps of the RNA life cycle. Nanodynamo is based on mathematical modelling following sequencing of native RNA from cellular fractions and polysomes. We have applied this workflow to triple-negative breast cancer cells, revealing widespread post-transcriptional RNA processing that is mutually exclusive with its co-transcriptional counterpart. We used Nanodynamo to unravel the coupling between transcription, processing, export, decay and translation machineries. We have identified a number of coupling interactions within and between the nucleus and cytoplasm that largely contribute to coordinating how cells respond to perturbations that affect gene expression programs. Nanodynamo will be instrumental in unravelling the determinants and regulatory processes involved in the coordination of gene expression responses.

Suicidality poses a significant public health threat and stands as a leading cause of death and disability. Aside from committed suicides, a substantial portion of suicidal behaviors comprises suicide attempts and suicidal ideation. These events may be characterized by a non-fatal outcome, shedding light on the possibility of recurrence. The objectives of the present study were to assess hospitalization rate trends related to any suicidal event and to elucidate the risk factors associated with recurrent suicidal behaviors. In this population-based study, an observational descriptive analysis was conducted on all hospital discharge forms (HDRs, Italian SDO) registered for the residents of the Veneto Region from 2012 to 2021. Cases of attempted suicide (AS) and suicidal ideation (SI) were defined according to ICD coding. Age-standardized hospitalization rates were computed with the direct method. Join Point Regression was used to assess the significance of variations in trends. Factor risks for the reiteration of suicidal behaviors were assessed by multivariate logistic regression. Higher prevalence of SI occurred among individuals under 40 years of age and those affected by psychiatric disorders. Conversely, among individuals aged 60 and above, AS was more common. SI turned out to be associated with a higher likelihood of reiteration compared to AS. Individuals suffering from personality disorders and those with a history of AS as index case exhibited increased risk for the reiteration of AS. Females, younger individuals, and individuals experiencing SI as first episode were instead identified as more likely to repeat this form of suicidal behavior. Contemporary economic and environmental crises, a recent pandemic, and numerous conflicts represent significant additional menaces to mental well-being. Our analysis highlights a concerning positive trend in suicide attempts and ideations, underscoring the imperative for Public Health Systems to implement targeted preventive strategies and mental health promotion campaigns. In the absence of structured suicide registries, we demonstrated that HDRs can serve as an invaluable foundation for preventionists to address the phenomenon and strategically plan interventions.

Abstract Experimental studies identified a role of neuroinflammation in the pathogenesis of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). However, the role of inflammatory molecules as diagnostic and prognostic biomarkers in patients with ALS is unclear. In this cross-sectional study, the cerebrospinal fluid (CSF) levels of a set of inflammatory cytokines and chemokines were analyzed in 56 newly diagnosed ALS patients and in 47 age- and sex-matched control patients without inflammatory or degenerative neurological disorders. The molecules analyzed included: interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-17, granulocyte colony stimulating factor (GCSF), macrophage inflammatory protein (MIP)-1a, MIP-1b, tumor necrosis factors (TNF), eotaxin. Principal component analysis (PCA) was used to explore possible associations between CSF molecules and ALS diagnosis. In addition, we analyzed the association between CSF cytokine profiles and clinical characteristics, including the disease progression rate score, and peripheral inflammation assessed using the Neutrophil-to-lymphocyte ratio (NLR). PCA identified six principal components (PCs) explaining 70.67% of the total variance in the CSF cytokine set. The principal component (PC1) explained 26.8% of variance and showed a positive load with CSF levels of IL-9, IL-4, GCSF, IL-7, IL-17, IL-13, IL-6, IL-1β, TNF, and IL-2. Logistic regression showed a significant association between PC1 and ALS diagnosis. In addition, in ALS patients, the same component was significantly associated with higher disease progression rate score and positively correlated with NLR. CSF inflammatory activation in present in ALS at the time of diagnosis and may characterize patients at higher risk for disease progression.

This article aims to organize some thoughts on the materiality of water courses and forests for rural individuals in different Brazilian territories and the relationship between rural schools and Agroecology during the COVID-19 pandemic. The analysis, based on data from 2020 and 2021, investigates how schools and their embeddedness contributed or could contribute to the construction of another agri-food system based on the principles of Agroecology. The methodological framework centered on surveying methods, literature review, and interviews with teachers from rural schools. The data point to the importance of schools in guaranteeing the food security of many families, in collective solidarity actions development, and in the production of pedagogical alternatives based on the critical understanding of the students' reality, which also are central elements for Agroecology practices.

Abstract Structural colors arise from selective light interaction with (nano)structures, which give them advantages over pigmented colors such as resistance to fading and possibility to be fabricated out of traditional low-cost and non-toxic materials. Since the color arises from the photonic (nano)structures, different structural features can impact their photonic response and thus, their color. Therefore, the detailed characterization of their structural features is crucial for further improvement of structural colors. In this work, we present a detailed multi-scale structural characterization of ceramic-based photonic glasses by using a combination of high-resolution ptychographic X-ray computed tomography and small angle X-ray scattering. Our results uncover the structure-processing-properties’ relationships of such nanoparticles-based photonic glasses and point out to the need of a review of the structural features used in simulation models concomitantly with the need for further investigations by experimentalists, where we point out exactly which structural features need to be improved.

BACKGROUND: We hypothesized that treatment delays might be an effect modifier regarding risks and benefits of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT). METHODS: We used the dataset of the SWIFT-DIRECT trial, which randomized 408 patients to IVT+MT or MT alone. Potential interactions between assignment to IVT+MT and expected time from onset-to-needle (OTN) as well as expected time from door-to-needle (DTN) were included in regression models. The primary outcome was functional independence (modified Rankin Scale (mRS) 0-2) at 3 months. Secondary outcomes included mRS shift, mortality, recanalization rates, and (symptomatic) intracranial hemorrhage at 24 hours. RESULTS: We included 408 patients (IVT+MT 207, MT 201, median age 72 years (IQR 64-81), 209 (51.2%) female). The expected median OTN and DTN were 142 min and 54 min in the IVT+MT group and 129 min and 51 min in the MT alone group. Overall, there was no significant interaction between OTN and bridging IVT assignment regarding either the functional (adjusted OR (aOR) 0.76, 95% CI 0.45 to 1.30) and safety outcomes or the recanalization rates. Analysis of in-hospital delays showed no significant interaction between DTN and bridging IVT assignment regarding the dichotomized functional outcome (aOR 0.48, 95% CI 0.14 to 1.62), but the shift and mortality analyses suggested a greater benefit of IVT when in-hospital delays were short. CONCLUSIONS: We found no evidence that the effect of bridging IVT on functional independence is modified by overall or in-hospital treatment delays. Considering its low power, this subgroup analysis could have missed a clinically important effect, and exploratory analysis of secondary clinical outcomes indicated a potentially favorable effect of IVT with shorter in-hospital delays. Heterogeneity of the IVT effect size before MT should be further analyzed in individual patient meta-analysis of comparable trials. TRIAL REGISTRATION NUMBER: URL: https://www. CLINICALTRIALS: gov ; Unique identifier: NCT03192332.

Background and aimsTo investigate the prognostic value of blood neurofilament light chain protein (NfL) levels in the acute phase of coronavirus disease 2019 (COVID-19).MethodsWe conducted an individual participant data (IPD) meta-analysis after screening on MEDLINE and Scopus to May 23rd 2022. We included studies with hospitalized adult COVID-19 patients without major COVID-19-associated central nervous system (CNS) manifestations and with a measurement of blood NfL in the acute phase as well as data regarding at least one clinical outcome including intensive care unit (ICU) admission, need of mechanical ventilation (MV) and death. We derived the age-adjusted measures NfL Z scores and conducted mixed-effects modelling to test associations between NfL Z scores and other variables, encompassing clinical outcomes. Summary receiver operating characteristic curves (SROCs) were used to calculate the area under the curve (AUC) for blood NfL.ResultsWe identified 382 records, of which 7 studies were included with a total of 669 hospitalized COVID-19 cases (mean age 66.2 ± 15.0 years, 68.1% males). Median NfL Z score at admission was elevated compared to the age-corrected reference population (2.37, IQR: 1.13-3.06, referring to 99th percentile in healthy controls). NfL Z scores were significantly associated with disease duration and severity. Higher NfL Z scores were associated with a higher likelihood of ICU admission, need of MV, and death. SROCs revealed AUCs of 0.74, 0.80 and 0.71 for mortality, need of MV and ICU admission, respectively.ConclusionsBlood NfL levels were elevated in the acute phase of COVID-19 patients without major CNS manifestations and associated with clinical severity and poor outcome. The marker might ameliorate the performance of prognostic multivariable algorithms in COVID-19.